Abstract: Postal screening has not previously been validated as a method for identifying fall and fracture risk in community-dwelling populations. We examined prognostic performance of a postal risk screener used in the UK Prevention of Falls Injury Trial (PreFIT; ISRCTN71002650), to predict any fall, recurrent falls, and fractures over 12 months. We tested whether adding variables would improve screener performance. Methods Nine thousand eight hundred and eight community-dwelling participants, aged 70 years and older, and 63 general practices in the UK National Health Service (NHS) were included in a large, pragmatic cluster randomised trial comparing screen and treat fall prevention interventions. The short postal screener was sent to all participants in the trial intervention arms as an A4 sheet to be completed and returned to the GP ( n  = 6,580). The postal screener items were embedded in the baseline pre-randomisation postal questionnaire for all arms of the trial ( n  = 9,808). We assessed discrimination and calibration using area under the curve (AUC). We identified additional predictors using data from the control arm and applied these coefficients to internal validation models in the intervention arm participants. We used logistic regression to identify additional predictor variables. Findings A total of 10,743 falls and 307 fractures were reported over 12 months. Over one third of participants 3,349/8,136 (41%) fell at least once over 12 month follow up. Response to the postal screener was high (5,779/6,580; 88%). Prediction models showed similar discriminatory ability in both control and intervention arms, with discrimination values for any fall AUC 0.67 (95% CI 0.65 to 0.68), and recurrent falls (AUC 0.71; 95% CI 0.69, 0.72) but poorer discrimination for fractures (AUC 0.60; 95% CI 0.56, 0.64). Additional predictor variables improved prediction of falls but had modest effect on fracture, where AUC rose to 0.71 (95% CI 0.67 to 0.74). Calibration slopes were very close to 1. Conclusion A short fall risk postal screener was acceptable for use in primary care but fall prediction was limited, although consistent with other tools. Fracture and fall prediction were only partially reliant on fall risk although were improved with the additional variables.

Abstract: To evaluate whether a structured exercise programme improved functional and health related quality of life outcomes compared with usual care for women at high risk of upper limb disability after breast cancer surgery. Design Multicentre, pragmatic, superiority, randomised controlled trial with economic evaluation. Setting 17 UK National Health Service cancer centres. Participants 392 women undergoing breast cancer surgery, at risk of postoperative upper limb morbidity, randomised (1:1) to usual care with structured exercise (n=196) or usual care alone (n=196). Interventions Usual care (information leaflets) only or usual care plus a physiotherapy led exercise programme, incorporating stretching, strengthening, physical activity, and behavioural change techniques to support adherence to exercise, introduced at 7-10 days postoperatively, with two further appointments at one and three months. Main outcome measures Disability of Arm, Hand and Shoulder (DASH) questionnaire at 12 months, analysed by intention to treat. Secondary outcomes included DASH subscales, pain, complications, health related quality of life, and resource use, from a health and personal social services perspective. Results Between 26 January 2016 and 31 July 2017, 951 patients were screened and 392 (mean age 58.1 years) were randomly allocated, with 382 (97%) eligible for intention to treat analysis. 181 (95%) of 191 participants allocated to exercise attended at least one appointment. Upper limb function improved after exercise compared with usual care (mean DASH 16.3 (SD 17.6) for exercise (n=132); 23.7 (22.9) usual care (n=138); adjusted mean difference 7.81, 95% confidence interval 3.17 to 12.44; P=0.001). Secondary outcomes favoured exercise over usual care, with lower pain intensity at 12 months (adjusted mean difference on numerical rating scale −0.68, −1.23 to −0.12; P=0.02) and fewer arm disability symptoms at 12 months (adjusted mean difference on Functional Assessment of Cancer Therapy-Breast+4 (FACT-B+4) −2.02, −3.11 to −0.93; P=0.001). No increase in complications, lymphoedema, or adverse events was noted in participants allocated to exercise. Exercise accrued lower costs per patient (on average −£387 (€457; $533) (95% confidence interval −£2491 to £1718; 2015 pricing) and was cost effective compared with usual care. Conclusions The PROSPER exercise programme was clinically effective and cost effective and reduced upper limb disability one year after breast cancer treatment in patients at risk of treatment related postoperative complications. Trial registration ISRCTN Registry ISRCTN35358984 .

Abstract: Falls and fractures are a major problem. Objectives To investigate the clinical effectiveness and cost-effectiveness of alternative falls prevention interventions. Design Three-arm, pragmatic, cluster randomised controlled trial with parallel economic analysis. The unit of randomisation was the general practice. Setting Primary care. Participants People aged ≥ 70 years. Interventions All practices posted an advice leaflet to each participant. Practices randomised to active intervention arms (exercise and multifactorial falls prevention) screened participants for falls risk using a postal questionnaire. Active treatments were delivered to participants at higher risk of falling. Main outcome measures The primary outcome was fracture rate over 18 months, captured from Hospital Episode Statistics, general practice records and self-report. Secondary outcomes were falls rate, health-related quality of life, mortality, frailty and health service resource use. Economic evaluation was expressed in terms of incremental cost per quality-adjusted life-year and incremental net monetary benefit. Results Between 2011 and 2014, we randomised 63 general practices (9803 participants): 21 practices (3223 participants) to advice only, 21 practices (3279 participants) to exercise and 21 practices (3301 participants) to multifactorial falls prevention. In the active intervention arms, 5779 out of 6580 (87.8%) participants responded to the postal fall risk screener, of whom 2153 (37.3%) were classed as being at higher risk of falling and invited for treatment. The rate of intervention uptake was 65% (697 out of 1079) in the exercise arm and 71% (762 out of 1074) in the multifactorial falls prevention arm. Overall, 379 out of 9803 (3.9%) participants sustained a fracture. There was no difference in the fracture rate between the advice and exercise arms (rate ratio 1.20, 95% confidence interval 0.91 to 1.59) or between the advice and multifactorial falls prevention arms (rate ratio 1.30, 95% confidence interval 0.99 to 1.71). There was no difference in falls rate over 18 months (exercise arm: rate ratio 0.99, 95% confidence interval 0.86 to 1.14; multifactorial falls prevention arm: rate ratio 1.13, 95% confidence interval 0.98 to 1.30). A lower rate of falls was observed in the exercise arm at 8 months (rate ratio 0.78, 95% confidence interval 0.64 to 0.96), but not at other time points. There were 289 (2.9%) deaths, with no differences by treatment arm. There was no evidence of effects in prespecified subgroup comparisons, nor in nested intention-to-treat analyses that considered only those at higher risk of falling. Exercise provided the highest expected quality-adjusted life-years (1.120), followed by advice and multifactorial falls prevention, with 1.106 and 1.114 quality-adjusted life-years, respectively. NHS costs associated with exercise (£3720) were lower than the costs of advice (£3737) or of multifactorial falls prevention (£3941). Although incremental differences between treatment arms were small, exercise dominated advice, which in turn dominated multifactorial falls prevention. The incremental net monetary benefit of exercise relative to treatment valued at £30,000 per quality-adjusted life-year is modest, at £191, and for multifactorial falls prevention is £613. Exercise is the most cost-effective treatment. No serious adverse events were reported. Limitations The rate of fractures was lower than anticipated. Conclusions Screen-and-treat falls prevention strategies in primary care did not reduce fractures. Exercise resulted in a short-term reduction in falls and was cost-effective. Future work Exercise is the most promising intervention for primary care. Work is needed to ensure adequate uptake and sustained effects. Trial registration Current Controlled Trials ISRCTN71002650. 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. 34. See the NIHR Journals Library website for further project information.

Abstract: Fractures are rare events and can occur because of a fall. Fracture counts are distinct from other count data in that these data are positively skewed, inflated by excess zero counts, and events can recur over time. Analytical methods used to assess fracture data and account for these characteristics are limited in the literature. Methods Commonly used models for count data include Poisson regression, negative binomial regression, hurdle regression, and zero-inflated regression models. In this paper, we compare four alternative statistical models to fit fracture counts using data from a large UK based clinical trial evaluating the clinical and cost-effectiveness of alternative falls prevention interventions in older people (Prevention of Falls Injury Trial; PreFIT). Results The values of Akaike information criterion and Bayesian information criterion, the goodness-of-fit statistics, were the lowest for negative binomial model. The likelihood ratio test of no dispersion in the data showed strong evidence of dispersion (chi-square = 225.68, p -value  〈  0.001). This indicates that the negative binomial model fits the data better compared to the Poisson regression model. We also compared the standard negative binomial regression and mixed effects negative binomial models. The LR test showed no gain in fitting the data using mixed effects negative binomial model (chi-square = 1.67, p -value = 0.098) compared to standard negative binomial model. Conclusions The negative binomial regression model was the most appropriate and optimal fit model for fracture count analyses. Trial registration The PreFIT trial was registered as ISRCTN71002650.

Abstract: Upper limb problems are common after breast cancer treatment. Objectives To investigate the clinical effectiveness and cost-effectiveness of a structured exercise programme compared with usual care on upper limb function, health-related outcomes and costs in women undergoing breast cancer surgery. Design This was a two-arm, pragmatic, randomised controlled trial with embedded qualitative research, process evaluation and parallel economic analysis; the unit of randomisation was the individual (allocated ratio 1 : 1). Setting Breast cancer centres, secondary care. Participants Women aged ≥ 18 years who had been diagnosed with breast cancer and were at higher risk of developing shoulder problems. Women were screened to identify their risk status. Interventions All participants received usual-care information leaflets. Those randomised to exercise were referred to physiotherapy for an early, structured exercise programme (three to six face-to-face appointments that included strengthening, physical activity and behavioural change strategies). Main outcome measures The primary outcome was upper limb function at 12 months as assessed using the Disabilities of Arm, Hand and Shoulder questionnaire. Secondary outcomes were function (Disabilities of Arm, Hand and Shoulder questionnaire subscales), pain, complications (e.g. wound-related complications, lymphoedema), health-related quality of life (e.g. EuroQol-5 Dimensions, five-level version; Short Form questionnaire-12 items), physical activity and health service resource use. The economic evaluation was expressed in terms of incremental cost per quality-adjusted life-year and incremental net monetary benefit gained from an NHS and Personal Social Services perspective. Participants and physiotherapists were not blinded to group assignment, but data collectors were blinded. Results Between 2016 and 2017, we randomised 392 participants from 17 breast cancer centres across England: 196 (50%) to the usual-care group and 196 (50%) to the exercise group. Ten participants (10/392; 3%) were withdrawn at randomisation and 32 (8%) did not provide complete baseline data. A total of 175 participants (89%) from each treatment group provided baseline data. Participants’ mean age was 58.1 years (standard deviation 12.1 years; range 28–88 years). Most participants had undergone axillary node clearance surgery (327/392; 83%) and 317 (81%) had received radiotherapy. Uptake of the exercise treatment was high, with 181 out of 196 (92%) participants attending at least one physiotherapy appointment. Compliance with exercise was good: 143 out of 196 (73%) participants completed three or more physiotherapy sessions. At 12 months, 274 out of 392 (70%) participants returned questionnaires. Improvement in arm function was greater in the exercise group [mean Disabilities of Arm, Hand and Shoulder questionnaire score of 16.3 (standard deviation 17.6)] than in the usual-care group [mean Disabilities of Arm, Hand and Shoulder questionnaire score of 23.7 (standard deviation 22.9)] at 12 months for intention-to-treat (adjusted mean difference Disabilities of Arm, Hand and Shoulder questionnaire score of –7.81, 95% confidence interval –12.44 to –3.17; p  = 0.001) and complier-average causal effect analyses (adjusted mean difference –8.74, 95% confidence interval –13.71 to –3.77; p  ≤ 0.001). At 12 months, pain scores were lower and physical health-related quality of life was higher in the exercise group than in the usual-care group (Short Form questionnaire-12 items, mean difference 4.39, 95% confidence interval 1.74 to 7.04; p  = 0.001). We found no differences in the rate of adverse events or lymphoedema over 12 months. The qualitative findings suggested that women found the exercise programme beneficial and enjoyable. Exercise accrued lower costs (–£387, 95% CI –£2491 to £1718) and generated more quality-adjusted life years (0.029, 95% CI 0.001 to 0.056) than usual care over 12 months. The cost-effectiveness analysis indicated that exercise was more cost-effective and that the results were robust to sensitivity analyses. Exercise was relatively cheap to implement (£129 per participant) and associated with lower health-care costs than usual care and improved health-related quality of life. Benefits may accrue beyond the end of the trial. Limitations Postal follow-up was lower than estimated; however, the study was adequately powered. No serious adverse events directly related to the intervention were reported. Conclusions This trial provided robust evidence that referral for early, supported exercise after breast cancer surgery improved shoulder function in those at risk of shoulder problems and was associated with lower health-care costs than usual care and improved health-related quality of life. Future work Future work should focus on the implementation of exercise programmes in clinical practice for those at highest risk of shoulder problems. Trial registration This trial is registered as ISRCTN35358984. 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. 26, No. 15. See the NIHR Journals Library website for further project information.

Abstract: 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. Trial registration ISRCTN71002650 .