Validity and repeatability of a simple index derived from the short physical activity questionnaire used in the European Prospective Investigation into Cancer and Nutrition (EPIC) study

Original article can be found at: http://journals.cambridge.org/action/displayJournal?jid=PHN Copyright The Authors. DOI: 10.1079/PHN2002439Peer reviewe

Intramedullary nail fixation versus locking plate fixation for adults with a fracture of the distal tibia : the UK FixDT RCT

Background The best treatment for fractures of the distal tibia remains controversial. Most of these fractures require surgical fixation, but the outcomes are unpredictable and complications are common. Objectives To assess disability, quality of life, complications and resource use in patients treated with intramedullary (IM) nail fixation versus locking plate fixation in the 12 months following a fracture of the distal tibia. Design This was a multicentre randomised trial. Setting The trial was conducted in 28 UK acute trauma centres from April 2013 to final follow-up in February 2017. Participants In total, 321 adult patients were recruited. Participants were excluded if they had open fractures, fractures involving the ankle joint, contraindication to nailing or inability to complete questionnaires. Interventions IM nail fixation (n = 161), in which a metal rod is inserted into the hollow centre of the tibia, versus locking plate fixation (n = 160), in which a plate is attached to the surface of the tibia with fixed-angle screws. Main outcome measures The primary outcome measure was the Disability Rating Index (DRI) score, which ranges from 0 points (no disability) to 100 points (complete disability), at 6 months with a minimum clinically important difference of 8 points. The DRI score was also collected at 3 and 12 months. The secondary outcomes were the Olerud–Molander Ankle Score (OMAS), quality of life as measured using EuroQol-5 Dimensions (EQ-5D), complications such as infection, and further surgery. Resource use was collected to inform the health economic evaluation. Results Participants had a mean age of 45 years (standard deviation 16.2 years), were predominantly male (61%, 197/321) and had experienced traumatic injury after a fall (69%, 223/321). There was no statistically significant difference in DRI score at 6 months [IM nail fixation group, mean 29.8 points, 95% confidence interval (CI) 26.1 to 33.7 points; locking plate group, mean 33.8 points, 95% CI 29.7 to 37.9 points; adjusted difference, 4.0 points, 95% CI –1.0 to 9.0 points; p = 0.11]. There was a statistically significant difference in DRI score at 3 months in favour of IM nail fixation (IM nail fixation group, mean 44.2 points, 95% CI 40.8 to 47.6 points; locking plate group, mean 52.6 points, 95% CI 49.3 to 55.9 points; adjusted difference 8.8 points, 95% CI 4.3 to 13.2 points; p < 0.001), but not at 12 months (IM nail fixation group, mean 23.1 points, 95% CI 18.9 to 27.2 points; locking plate group, 24.0 points, 95% CI 19.7 to 28.3 points; adjusted difference 1.9 points, 95% CI –3.2 to 6.9 points; p = 0.47). Secondary outcomes showed the same pattern, including a statistically significant difference in mean OMAS and EQ-5D scores at 3 and 6 months in favour of IM nail fixation. There were no statistically significant differences in complications, including the number of postoperative infections (13% in the locking plate group and 9% in the IM nail fixation group). Further surgery was more common in the locking plate group (12% in locking plate group and 8% in IM nail fixation group at 12 months). The economic evaluation showed that IM nail fixation provided a slightly higher quality of life in the 12 months after injury and at lower cost and, therefore, it was cost-effective compared with locking plate fixation. The probability of cost-effectiveness for IM nail fixation exceeded 90%, regardless of the value of the cost-effectiveness threshold. Limitations As wound dressings after surgery are clearly visible, it was not possible to blind the patients to their treatment allocation. This evidence does not apply to intra-articular (pilon) fractures of the distal tibia. Conclusions Among adults with an acute fracture of the distal tibia who were randomised to IM nail fixation or locking plate fixation, there were similar disability ratings at 6 months. However, recovery across all outcomes was faster in the IM nail fixation group and costs were lower

Aerobic and strength training exercise programme for cognitive impairment in people with mild to moderate dementia : the DAPA RCT

Background Approximately 670,000 people in the UK have dementia. Previous literature suggests that physical exercise could slow dementia symptom progression. Objectives To estimate the clinical effectiveness and cost-effectiveness of a bespoke exercise programme, in addition to usual care, on the cognitive impairment (primary outcome), function and health-related quality of life (HRQoL) of people with mild to moderate dementia (MMD) and carer burden and HRQoL. Design Intervention development, systematic review, multicentred, randomised controlled trial (RCT) with a parallel economic evaluation and qualitative study. Setting 15 English regions. Participants People with MMD living in the community. Intervention A 4-month moderate- to high-intensity, structured exercise programme designed specifically for people with MMD, with support to continue unsupervised physical activity thereafter. Exercises were individually prescribed and progressed, and participants were supervised in groups. The comparator was usual practice. Main outcome measures The primary outcome was the Alzheimer’s Disease Assessment Scale – Cognitive Subscale (ADAS-Cog). The secondary outcomes were function [as measured using the Bristol Activities of Daily Living Scale (BADLS)], generic HRQoL [as measured using the EuroQol-5 Dimensions, three-level version (EQ-5D-3L)], dementia-related QoL [as measured using the Quality of Life in Alzheimer’s Disease (QoL-AD) scale], behavioural symptoms [as measured using the Neuropsychiatric Inventory (NPI)], falls and fractures, physical fitness (as measured using the 6-minute walk test) and muscle strength. Carer outcomes were HRQoL (Quality of Life in Alzheimer’s Disease) (as measured using the EQ-5D-3L) and carer burden (as measured using the Zarit Burden Interview). The economic evaluation was expressed in terms of incremental cost per quality-adjusted life-year (QALY) gained from a NHS and Personal Social Services perspective. We measured health and social care use with the Client Services Receipt Inventory. Participants were followed up for 12 months. Results Between February 2013 and June 2015, 494 participants were randomised with an intentional unequal allocation ratio: 165 to usual care and 329 to the intervention. The mean age of participants was 77 years [standard deviation (SD) 7.9 years], 39% (193/494) were female and the mean baseline ADAS-Cog score was 21.5 (SD 9.0). Participants in the intervention arm achieved high compliance rates, with 65% (214/329) attending between 75% and 100% of sessions. Outcome data were obtained for 85% (418/494) of participants at 12 months, at which point a small, statistically significant negative treatment effect was found in the primary outcome, ADAS-Cog (patient reported), with a mean difference of –1.4 [95% confidence interval (CI) –2.62 to –0.17]. There were no treatment effects for any of the other secondary outcome measures for participants or carers: for the BADLS there was a mean difference of –0.6 (95% CI –2.05 to 0.78), for the EQ-5D-3L a mean difference of –0.002 (95% CI –0.04 to 0.04), for the QoL-AD scale a mean difference of 0.7 (95% CI –0.21 to 1.65) and for the NPI a mean difference of –2.1 (95% CI –4.83 to 0.65). Four serious adverse events were reported. The exercise intervention was dominated in health economic terms. Limitations In the absence of definitive guidance and rationale, we used a mixed exercise programme. Neither intervention providers nor participants could be masked to treatment allocation. Conclusions This is a large well-conducted RCT, with good compliance to exercise and research procedures. A structured exercise programme did not produce any clinically meaningful benefit in function or HRQoL in people with dementia or on carer burden

The cost-effectiveness of adding an ultrasound corticosteroid and local anaesthetic injection to advice and education for hip osteoarthritis.

ObjectivesEvidence for the comparative cost-effectiveness of intra-articular corticosteroid injection in people with hip osteoarthritis (OA) remains unclear. This study investigated the cost-effectiveness of best current treatment (BCT) comprising advice and education plus a single ultrasound-guided intra-articular hip injection (USGI) of 40 mg triamcinolone acetonide and 4 ml 1% lidocaine hydrochloride (BCT+US-T) versus BCT alone.MethodsA trial-based cost-utility analysis of BCT+US-T compared with BCT was undertaken over 6 months. Patient-level cost data were obtained, and effectiveness was measured in terms of quality-adjusted life years (QALYs), allowing the calculation of cost per QALY gained from a United Kingdom (UK) National Health Service (NHS) perspective.ResultsBCT+US-T was associated with lower mean NHS costs (BCT+US-T minus BCT: £-161.6, 95% CI: £-583.95 to £54.18) and small but significantly higher mean QALYs than BCT alone over 6 months (BCT+US-T minus BCT: 0.0487, 95% CI: 0.0091, 0.0886). In the base case, BCT+US-T was the most cost-effective and dominated BCT alone. Differences in total costs were driven by number of visits to NHS consultants, private physiotherapists, and chiropractors, and hip surgery, which were more common with BCT alone than BCT+US-T.ConclusionIntra-articular corticosteroid injection plus BCT (BCT+US-T) for patients with hip OA results in lower costs and better outcomes, and is highly cost-effective, compared with BCT alone.Trial registrationEudraCT: 2014-003412-37 (August 8, 2015) and registered with Current Controlled Trials: ISRCTN 50550256 (July 28, 2015).Trial protocolFull details of the trial protocol can be found in the Supplementary Appendix, available with the full text of this article at https://bmcmusculoskeletdisord.biomedcentral.com/articles/10.1186/s12891-018-2153-0#citeas.Doidoi.org/10.1186/s12891-018-2153-0

Pre-hospital assessment of the role of adrenaline : measuring the effectiveness of drug administration in cardiac arrest (PARAMEDIC-2) : trial protocol

Despite its use since the 1960s, the safety or effectiveness of adrenaline as a treatment for cardiac arrest has never been comprehensively evaluated in a clinical trial. Although most studies have found that adrenaline increases the chance of return of spontaneous circulation for short periods, many studies found harmful effects on the brain and raise concern that adrenaline may reduce overall survival and/or good neurological outcome. The PARAMEDIC-2 trial seeks to determine if adrenaline is safe and effective in out-of-hospital cardiac arrest. This is a pragmatic, individually randomised, double blind, controlled trial with a parallel economic evaluation. Participants will be eligible if they are in cardiac arrest in the out-of-hospital environment and advanced life support is initiated. Exclusions are cardiac arrest as a result of anaphylaxis or life threatening asthma, and patient known or appearing to be under 16 or pregnant. 8000 participants treated by 5 UK ambulance services will be randomised between December 2014 and August 2017 to adrenaline (intervention) or placebo (control) through opening pre-randomised drug packs. Clinical outcomes are survival to 30 days (primary outcome), hospital discharge, 3, 6 and 12 months, health related quality of life, and neurological and cognitive outcomes (secondary outcomes). Trial registration (ISRCTN73485024)

The importance of different frailty domains in a population based sample in England

Background: The aim was to estimate the prevalence of frailty and relative contribution of physical/balance, nutritive, cognitive and sensory frailty to important adverse health states (falls, physical activity levels, outdoor mobility, problems in self-care or usual activities, and lack of energy or accomplishment) in an English cohort by age and sex. Methods: Analysis of baseline data from a cohort of 9803 community-dwelling participants in a clinical trial. The sample was drawn from a random selection of all people aged 70 or more registered with 63 general practices across England. Data were collected by postal questionnaire. Frailty was measured with the Strawbridge questionnaire. We used cross sectional, multivariate logistic regression to estimate the association between frailty domains and known correlates and adjusted for age. Some models were stratified by sex. Results: Mean age of participants was 78 years (sd 5.7), range 70 to 101 and 47.5% (4653/9803) were men. The prevalence of overall frailty was 20.7% (2005/9671) and there was no difference in prevalence by sex (Odds Ratio 0.98; 95% Confidence Interval 0.89 to 1.08). Sensory frailty was the most common and this was reported by more men (1823/4586) than women (1469/5056; Odds Ratio for sensory frailty 0.62, 95% Confidence Interval 0.57 to 0.68). Men were less likely than women to have physical or nutritive frailty. Physical frailty had the strongest independent associations with adverse health states. However, sensory frailty was independently associated with falls, less frequent walking, problems in self-care and usual activities, lack of energy and accomplishment. Conclusions: Physical frailty was more strongly associated with adverse health states, but sensory frailty was much more common. The health gain from intervention for sensory frailty in England is likely to be substantial, particularly for older men. Sensory frailty should be explored further as an important target of intervention to improve health outcomes for older people both at clinical and population level.This article is freely available via Open Access. Click on the Publisher URL to access it via the publisher's site.08/14/41/DH_/Department of Health/United Kingdom Project number 08/14/41/Health Technology Assessment Programmepre-print, post-print, publisher's version/PD

Dementia and Physical Activity (DAPA) - an exercise intervention to improve cognition in people with mild to moderate dementia: Study protocol for a randomized controlled trial

Background: Dementia is more common in older than in younger people, and as a result of the ageing of the population in developed countries, it is becoming more prevalent. Drug treatments for dementia are limited, and the main support offered to people with dementia and their families is generally services to mitigate against loss of function. Physical exercise is a candidate non-pharmacological treatment for dementia. Methods/Design: DAPA is a randomised controlled trial funded by the National Institute for Health Research Health Technology Assessment programme to estimate the effect of a 4-month, moderate- to hard-intensity exercise training programme and subsequent advice to remain active, on cognition (primary outcome) at 12 months in people with mild to moderate dementia. Community-dwelling participants (with their carers where possible), who are able to walk 3 metres without human assistance, able to undertake an exercise programme and do not have any unstable or terminal illness are recruited. Participants are then randomised by an independent statistician using a computerised random number generator to usual care or exercise at a 2:1 ratio in favour of exercise. The exercise intervention comprises 29, 1-hour-long exercise classes, run twice weekly at suitable venues such as leisure centres, which include aerobic exercise (on static bikes) and resistance exercise (using weights). Goals for independent exercise are set while the classes are still running, and supported thereafter with phone calls. The primary outcome is measured using ADAS-cog. Secondary outcome measures include behavioural symptoms, functional ability, quality of life and carer burden. Primary and secondary outcomes will be measured at baseline and at 6 and 12 months after randomisation, by researchers masked to participant randomisation in the participants' own homes. An economic evaluation will be carried out in parallel to the RCT, as will a qualitative study capturing the experiences of participants, carers and staff delivering the intervention. Discussion: The DAPA study will be the first large, randomised trial of the cognitive effects of exercise on people with dementia. The intervention is designed to be capable of being delivered within the constraints of NHS service provision, and the economic evaluation will allow assessment of its cost-effectiveness. Trial registration: DAPA was registered with the ISRCTN database on 29 July 2011, registration number ISRCTN32612072. © 2016 Atherton et al

Adrenaline to improve survival in out-of-hospital cardiac arrest : the PARAMEDIC2 RCT

Background Adrenaline has been used as a treatment for cardiac arrest for many years, despite uncertainty about its effects on long-term outcomes and concerns that it may cause worse neurological outcomes. Objectives The objectives were to evaluate the effects of adrenaline on survival and neurological outcomes, and to assess the cost-effectiveness of adrenaline use. Design This was a pragmatic, randomised, allocation-concealed, placebo-controlled, parallel-group superiority trial and economic evaluation. Costs are expressed in Great British pounds and reported in 2016/17 prices. Setting This trial was set in five NHS ambulance services in England and Wales. Participants Adults treated for an out-of-hospital cardiac arrest were included. Patients were ineligible if they were pregnant, if they were aged < 16 years, if the cardiac arrest had been caused by anaphylaxis or life-threatening asthma, or if adrenaline had already been given. Interventions Participants were randomised to either adrenaline (1 mg) or placebo in a 1 : 1 allocation ratio by the opening of allocation-concealed treatment packs. Main outcome measures The primary outcome was survival to 30 days. The secondary outcomes were survival to hospital admission, survival to hospital discharge, survival at 3, 6 and 12 months, neurological outcomes and health-related quality of life through to 6 months. The economic evaluation assessed the incremental cost per quality-adjusted life-year gained from the perspective of the NHS and Personal Social Services. Participants, clinical teams and those assessing patient outcomes were masked to the treatment allocation. Results From December 2014 to October 2017, 8014 participants were assigned to the adrenaline (n = 4015) or to the placebo (n = 3999) arm. At 30 days, 130 out of 4012 participants (3.2%) in the adrenaline arm and 94 out of 3995 (2.4%) in the placebo arm were alive (adjusted odds ratio for survival 1.47, 95% confidence interval 1.09 to 1.97). For secondary outcomes, survival to hospital admission was higher for those receiving adrenaline than for those receiving placebo (23.6% vs. 8.0%; adjusted odds ratio 3.83, 95% confidence interval 3.30 to 4.43). The rate of favourable neurological outcome at hospital discharge was not significantly different between the arms (2.2% vs. 1.9%; adjusted odds ratio 1.19, 95% confidence interval 0.85 to 1.68). The pattern of improved survival but no significant improvement in neurological outcomes continued through to 6 months. By 12 months, survival in the adrenaline arm was 2.7%, compared with 2.0% in the placebo arm (adjusted odds ratio 1.38, 95% confidence interval 1.00 to 1.92). An adjusted subgroup analysis did not identify significant interactions. The incremental cost-effectiveness ratio for adrenaline was estimated at £1,693,003 per quality-adjusted life-year gained over the first 6 months after the cardiac arrest event and £81,070 per quality-adjusted life-year gained over the lifetime of survivors. Additional economic analyses estimated incremental cost-effectiveness ratios for adrenaline at £982,880 per percentage point increase in overall survival and £377,232 per percentage point increase in neurological outcomes over the first 6 months after the cardiac arrest. Limitations The estimate for survival with a favourable neurological outcome is imprecise because of the small numbers of patients surviving with a good outcome. Conclusions Adrenaline improved long-term survival, but there was no evidence that it significantly improved neurological outcomes. The incremental cost-effectiveness ratio per quality-adjusted life-year exceeds the threshold of £20,000–30,000 per quality-adjusted life-year usually supported by the NHS. Future work Further research is required to better understand patients’ preferences in relation to survival and neurological outcomes after out-of-hospital cardiac arrest and to aid interpretation of the trial findings from a patient and public perspective. Trial registration Current Controlled Trials ISRCTN73485024 and EudraCT 2014-000792-11. 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. 25, No. 25. See the NIHR Journals Library website for further project information

Eliciting salient beliefs in research on the theory of planned behaviour:The effect of question wording

The authors of the theory of reasoned action (TRA) and its extension, the theory of planned behaviour (TPB) recommend that researchers who use these theories to investigate the determinants of a given behaviour should first conduct an elicitation study to identify the modal salient beliefs in the target population. In spite of the importance accorded to salient beliefs by the TRA/TPB, the elicitation stage has received little research attention. This paper reports a detailed analysis of beliefs about "being more physically active in the next 12 months." A general population sample of 213 adults completed a questionnaire while attending a research centre for a series of tests. The findings showed that the beliefs that were elicited by questions designed to prompt affective outcomes (like or enjoy, dislike or hate) differed systematically from those that were elicited by the traditional questions designed to prompt instrumental outcomes (advantages and disadvantages). Whether this resulted in different final sets of modal salient beliefs was found to depend on the particular decision rule that was employed. An alternative decision rule is proposed, based on maximizing the degree of overlap between the modal set and the full set of salient beliefs generated by the sample. The index of overlap can be used to gauge the adequacy of using a modal set of a given size to represent the salient beliefs of the whole sample. In the current dataset, the optimal modal set for "advantages and disadvantages" was associated with only 26 percent overlap with the salient beliefs of the whole sample, which was judged to be insufficient. In such cases, a better strategy may be to ask participants to generate and rate their own beliefs