Perspectives of informal caregivers who support people following hip fracture surgery: a qualitative study embedded within the HIP HELPER feasibility trial.

OBJECTIVES: This study aims to illuminate the perspectives of informal caregivers who support people following hip fracture surgery. DESIGN: A qualitative study embedded within a now completed multicentre, feasibility randomised controlled trial (HIP HELPER). SETTING: Five English National Health Service hospitals. PARTICIPANTS: We interviewed 20 participants (10 informal caregivers and 10 people with hip fracture), following hip fracture surgery. This included one male and nine females who experienced a hip fracture; and seven male and three female informal caregivers. The median age was 72.5 years (range: 65-96 years), 71.0 years (range: 43-81 years) for people with hip fracture and informal caregivers, respectively. METHODS: Semistructured, virtual interviews were undertaken between November 2021 and March 2022, with caregiver dyads (person with hip fracture and their informal caregiver). Data were analysed thematically. FINDINGS: We identified two main themes: expectations of the informal caregiver role and reality of being an informal caregiver; and subthemes: expectations of care and services; responsibility and advocacy; profile of people with hip fracture; decision to be a caregiver; transition from hospital to home. CONCLUSION: Findings suggest informal caregivers do not feel empowered to advocate for a person's recovery or navigate the care system, leading to increased and unnecessary stress, anxiety and frustration when supporting the person with hip fracture. We suggest that a tailored information giving on the recovery pathway, which is responsive to the caregiving population (ie, considering the needs of male, younger and more active informal caregivers and people with hip fracture) would smooth the transition from hospital to home. TRIAL REGISTRATION NUMBER: ISRCTN13270387.Cite Now.

Survival of revision ankle arthroplasty.

Aims: The number of revision total ankle arthroplasties (TAAs) which are undertaken is increasing. Few studies have reported the survival after this procedure. The primary aim of this study was to analyze the survival of revision ankle arthroplasties using large datasets. Secondary aims were to summarize the demographics of the patients, the indications for revision TAA, further operations, and predictors of survival. Methods: The study combined data from the National Joint Registry and NHS Digital to report the survival of revision TAA. We have previously reported the failure rates and risk factors for failure after TAA, and the outcome of fusion after a failed TAA, using the same methodology. Survival was assessed using life tables and Kaplan Meier graphs. Cox proportional hazards regression models were fitted to compare failure rates. Results: A total of 228 patients underwent revision TAA. The mean follow-up was 2.6 years (SD 2.0). The mean time between the initial procedure and revision was 2.3 years (SD 1.8). The most commonly used implant was the Inbone which was used in 81 patients. A total of 29 (12.7%) failed; nine (3.9%) patients underwent a further revision, 19 (8.3%) underwent a fusion, and one (0.4%) had an amputation. The rate of survival was 95.4% (95% confidence interval (CI) 91.6 to 97.5) at one year, 87.7% (95% CI 81.9 to 91.7; n = 124) at three years and 77.5% (95% CI 66.9 to 85.0; n = 57) at five years. Revision-specific implants had a better survival than when primary implants were used at revision. A total of 50 patients (21.9%) had further surgery; 19 (8.3%) underwent reoperation in the first 12 months. Cox regression models were prepared. In crude analysis the only significant risk factors for failure were the use of cement (hazard ratio (HR) 3.02 (95% CI 1.13 to 8.09)) and the time since the primary procedure (HR 0.67 (95% CI 0.47 to 0.97)). No risk factors for failure were identified in multivariable Cox regression modelling. Conclusion: Revision TAAs have good medium term survival and low rates of further surgery. New modular revision implants appear to have improved the survival compared with the use of traditional primary implants at revision.

The Extent of Evidence Supporting the Effectiveness of Extended Reality Telerehabilitation on Different Qualitative and Quantitative Outcomes in Stroke Survivors: A Systematic Review.

Objective: To present the extent of evidence concerning the effectiveness of extended reality telerehabilitation and patients' experiences of using different types of virtual reality exercises at home. Methods: We included studies on virtual reality and augmented reality telerehabilitation published in English. Systematic searches were undertaken in PubMed, Web of Sciences, Medline, Embase, CINAHL, and PEDro, with no date limitations. We included only RCTs and qualitative studies exploring patients' experiences. Methodological quality was assessed using the Cochrane Risk of Bias assessment tool for quantitative papers and the CASP scale for qualitative studies. All results are presented narratively. Results: Thirteen studies, nine quantitative and four qualitative, were included, with one qualitative and seven quantitative having a high risk of bias. All studies reported that extended reality-based telerehabilitation may be effective compared to conventional exercises or other extended reality exercises. Seven quantitative studies focused on upper limb function. Qualitative papers suggested that VR exercises were perceived as feasible by patients. Conclusions: The literature suggests VR home exercises are feasible and potentially effective for patients after a stroke in the upper limb. Further high-quality studies are needed to examine the effectiveness of XR exercises early adoption on different qualitative and quantitative outcomes. Registration number: (CRD42022384356).

Fusion after a failed primary total ankle arthroplasty.

Aims: When a total ankle arthroplasty (TAA) fails, it can be converted to a fusion or a revision arthroplasty. Despite the increasing numbers of TAAs being undertaken, there is little information in the literature about the management of patients undergoing fusion following a failed TAA. The primary aim of this study was to analyze the survival of fusions following a failed TAA using a large dataset from the National Joint Registry (NJR). Methods: A data linkage study combined NJR and NHS Digital data. Failure of a TAA was defined as a fusion, revision to a further TAA, or amputation. Life tables and Kaplan-Meier graphs were used to record survival. Cox proportional hazards regression models were fitted to compare the rates of failure. Results: A total of 131 patients underwent fusion as a salvage procedure following TAA. Their mean age was 65.7 years (SD 10.6) and 73 (55.7%) were male. The mean follow-up was 47.5 months (SD 27.2). The mean time between TAA and fusion was 5.3 years (SD 2.7). Overall, 32 (24.4%) underwent reoperations other than revision and 29 (22.1%) failed. Of these 24 (18.3%) underwent revision of the fusion and five (3.8%) had a below-knee amputation. No patients underwent conversion to a further TAA. Failure usually occurred in the first three postoperative years with one-year survival of fusion being 96.0% (95% confidence interval (CI) 90.7 to 98.3) and three-year survival in 69 patients being 77.5% (95% CI 68.3 to 84.4). Conclusion: Salvage fusion after a failed TAA shows moderate rates of failure and reoperations. Nearly 25% of patients required revision within three years. This study is an extension of studies using the same methodology reporting the failure rates and risk factors for failure, which have recently been published, and also one reporting the outcome of revision TAA for a failed primary TAA, using the same methodology, which will shortly be published.

Risk Factors for Failure of Total Ankle Replacements: A Data Linkage Study Using the National Joint Registry and NHS Digital.

BACKGROUND: Despite the increasing numbers of ankle replacements, there remains debate about which patients should undergo an ankle replacement, and there are limited studies analyzing risk factors for failure of an ankle replacement. The primary aim of this study is to analyze the risk factors for failure of total ankle replacements. METHODS: A data linkage study combining the National Joint Registry (NJR) Data and NHS (National Health Service) Digital data was performed. The primary outcome of failure is defined as the removal or exchange of any components of the implanted device. Kaplan-Meier survival charts were used to illustrate survivorship. Multivariable Cox proportional hazards regression models were fitted to analyze potential risk factors for failures or ankle replacements. RESULTS: The overall 5-year survival was 90.2% (95% CI 89.2%-91.1%). In multivariable (adjusted) Cox regression models, only age (hazard ratio [HR] 0.96, 95% CI 0.94-0.97), body mass index (BMI; HR 1.03, 95% CI 1.01-1.06), and underlying etiology (HR 0.88, 95% CI 0.80-0.97) were associated with an increased risk of failure. CONCLUSION: This study demonstrates that younger patients and those with an increased BMI have an increased risk of failure of a primary ankle replacement. We also show that rheumatoid patients have higher survivorship than those with osteoarthritis. LEVEL OF EVIDENCE: Level III, retrospective cohort study.

How long do ankle arthroplasties last?

Despite the increasing numbers of ankle arthroplasties, there are limited studies on their survival and comparisons between different implants. The primary aim of this study was to determine the failure rates of primary ankle arthroplasties commonly used in the UK. A data linkage study combined National Joint Registry (NJR) data and NHS Digital data. The primary outcome of failure was defined as the removal or exchange of any components of the implanted device. Life tables and Kaplan-Meier survival charts were used to illustrate survivorship. Cox proportional hazards regression models were fitted to compare failure rates between 1 April 2010 and 31 December 2018. Overall, 5,562 primary ankle arthroplasties were recorded in the NJR. Linked data show a one-year survivorship of 98.8% (95% confidence interval (CI) 98.4% to 99.0%), five-year survival in 2,725 patients of 90.2% (95% CI 89.2% to 91.1%), and ten-year survival in 199 patients of 86.2% (95% CI 84.6% to 87.6%). The five-year survival for fixed-bearing implants was 94.3% (95% CI 91.3% to 96.3%) compared to 89.4% (95% CI 88.3% to 90.4%) for mobile-bearing implants. A Cox regression model for all implants with over 100 implantations using the implant with the best survivorship (Infinity) as the reference, only the STAR (hazard ratio (HR) 1.60 (95% CI 0.87 to 2.96)) and INBONE (HR 0.38 (95% CI 0.05 to 2.84)) did not demonstrate worse survival at three and five years. Ankle arthroplasties in the UK have a five-year survival rate of 90.2%, which is lower than recorded on the NJR, because we have shown that approximately one-third of ankle arthroplasty failures are not reported to the NJR. There are statistically significant differences in survival between different implants. Fixed-bearing implants appear to demonstrate higher survivorship than mobile-bearing implants.

Pulmonary Embolism, Mortality, and Medical Complications Following a Total Ankle Replacement: A Systematic Review and Meta-analysis.

BACKGROUND: There is sparse data on the incidence of thromboembolic and medical complications following total ankle replacements. The aim of this systematic review was to determine the risk of deep vein thrombosis and pulmonary embolism as well as mortality and medical complications following ankle replacements. METHODS: A systematic review was undertaken using all levels of evidence following PRISMA guidelines. Of the 1657 articles identified, 25 met the inclusion criteria. The inclusion criteria were a primary total ankle replacement with the recording of medical complications and/or thromboembolic events and/or mortality data. Two reviewers independently reviewed all articles. Quantitative methods were used to pool the percentages with complications across studies. RESULTS: The pooled percentage with reported symptomatic deep vein thrombosis across 18 studies was 0.07% (95% CI 0.001%-0.59%). The pooled percentage with reported postoperative pulmonary embolism across 8 studies was 0.01% (95% CI 0.001%-0.03%). The pooled postoperative reported mortality was 0.06% (95% CI 0.001%-0.24%). Other medical complications had low incidences. CONCLUSION: Our study indicates rates of reported thromboembolic events of less than 1 in 1000. Notably the level of evidence analyzed was mainly Level III and IV, likely underestimating the true incidence of these events because of recall and medical record limitations, and we had insufficient information on usage of chemoprophylaxis among these patients. LEVEL OF EVIDENCE: Level IV, systematic review based on all levels of evidence including case series.

Comparison of over-ground and treadmill perturbations for simulation of real-world slips and trips: A systematic review.

BACKGROUND: Trips and slips increase fall risk for young and older adults. To examine recovery responses, studies utilized treadmill and/or over-ground methods to simulate real-world perturbations. However, differences in the recovery response between treadmill and over-ground perturbations remain unexamined. RESEARCH QUESTION: To assess the current literature on the reactive recovery responses between over-ground- and split-belt treadmill trips and slips as well as the effect of aging on these responses. METHODS: PubMed, Medline, Web of Science, SCOPUS, and Cochrane databases were searched for publications examining trips and slips in healthy young, healthy older adults, and older adults who fall. Included articles were in English, full-text accessible, and biomechanically quantified the reactive recovery responses for slips and trips during either over-ground or split-belt treadmill protocols. The initial database search yielded 1075 articles and 31 articles were included after title, abstract, and full-text screening. RESULTS: For slips, 7 articles utilized lubricated surfaces while 5 articles used treadmills. Further, 3 studies examined differences between older and younger adults. For trips, 9 articles utilized obstacles and 7 used treadmills. Further, 4 articles examined differences between older and young adults and 1 article only examined older adults during over-ground trips. For both perturbations, treadmill and over-ground protocols demonstrated similar anteroposterior destabilization on the center of mass. In the mediolateral direction, over-ground slips consistently found a lateral destabilization while treadmill articles did not examine this direction. Foot placement recovery responses varied less for both perturbation directions on a treadmill compared to over-ground. SIGNIFICANCE: Although treadmill and over-ground perturbations destabilize the center of mass similarly, the recovery response to these perturbations were different on treadmills. Specifically, recovery responses were more consistent for both slips and trips on treadmills. As older adults have difficulty in perturbation recovery scaling, treadmills may be limited in their ability to investigate the variety of aging impairments on perturbation recovery responses.

Nonlinear Dynamic Measures of Walking in Healthy Older Adults: A Systematic Scoping Review.

BACKGROUND: Maintaining a healthy gait into old age is key to preserving the quality of life and reducing the risk of falling. Nonlinear dynamic analyses (NDAs) are a promising method of identifying characteristics of people who are at risk of falling based on their movement patterns. However, there is a range of NDA measures reported in the literature. The aim of this review was to summarise the variety, characteristics and range of the nonlinear dynamic measurements used to distinguish the gait kinematics of healthy older adults and older adults at risk of falling. METHODS: Medline Ovid and Web of Science databases were searched. Forty-six papers were included for full-text review. Data extracted included participant and study design characteristics, fall risk assessment tools, analytical protocols and key results. RESULTS: Among all nonlinear dynamic measures, Lyapunov Exponent (LyE) was most common, followed by entropy and then Fouquet Multipliers (FMs) measures. LyE and Multiscale Entropy (MSE) measures distinguished between older and younger adults and fall-prone versus non-fall-prone older adults. FMs were a less sensitive measure for studying changes in older adults' gait. Methodology and data analysis procedures for estimating nonlinear dynamic measures differed greatly between studies and are a potential source of variability in cross-study comparisons and in generating reference values. CONCLUSION: Future studies should develop a standard procedure to apply and estimate LyE and entropy to quantify gait characteristics. This will enable the development of reference values in estimating the risk of falling.

The effectiveness of rehabilitation interventions including outdoor mobility on older adults' physical activity, endurance, outdoor mobility and falls-related self-efficacy: systematic review and meta-analysis.

OBJECTIVE: To determine the effectiveness of community-based rehabilitation interventions which incorporate outdoor mobility on physical activity, endurance, outdoor mobility and falls-related self-efficacy in older adults. DESIGN: MEDLINE, Embase, CINAHL, PEDro and OpenGrey were searched systematically from inception to June 2021 for randomised controlled trials (RCTs) of community-based rehabilitation incorporating outdoor mobility on physical activity, endurance, outdoor mobility and/or falls-related self-efficacy in older adults. Duplicate screening, selection, extraction and appraisal were completed. Results were reported descriptively and with random-effects meta-analyses stratified by population (proactive [community-dwelling], reactive [illness/injury]). RESULTS: A total of 29 RCTs with 7,076 participants were identified (66% high bias for at least one domain). The outdoor mobility component was predominantly a walking programme with behaviour change. Rehabilitation for reactive populations increased physical activity (seven RCTs, 587 participants. Hedge's g 1.32, 95% CI: 0.31, 2.32), endurance (four RCTs, 392 participants. Hedges g 0.24; 95% CI: 0.04, 0.44) and outdoor mobility (two RCTs with 663 participants. Go out as much as wanted, likelihood of a journey) at intervention end versus usual care. Where reported, effects were preserved at follow-up. One RCT indicated a benefit of rehabilitation for proactive populations on moderate-to-vigorous activity and outdoor mobility. No effect was noted for falls-related self-efficacy, or other outcomes following rehabilitation for proactive populations. CONCLUSION: Reactive rehabilitation for older adults may include walking programmes with behaviour change techniques. Future research should address the potential benefit of a walking programme for proactive populations and address mobility-related anxiety as a barrier to outdoor mobility for both proactive and reactive populations.

Effectiveness of community-based rehabilitation interventions incorporating outdoor mobility on ambulatory ability and falls-related self-efficacy after hip fracture: a systematic review and meta-analysis.

There is limited evidence from 11 randomised controlled trials on the effect of rehabilitation interventions which incorporate outdoor mobility on ambulatory ability and/or self-efficacy after hip fracture. Outdoor mobility should be central (not peripheral) to future intervention studies targeting improvements in ambulatory ability. PURPOSE: Determine the extent to which outdoor mobility is incorporated into rehabilitation interventions after hip fracture. Synthesise the evidence for the effectiveness of these interventions on ambulatory ability and falls-related self-efficacy. METHODS: Systematic search of MEDLINE, Embase, PsychInfo, CINAHL, PEDro and OpenGrey for published and unpublished randomised controlled trials (RCTs) of community-based rehabilitation interventions incorporating outdoor mobility after hip fracture from database inception to January 2021. Exclusion of protocols, pilot/feasibility studies, secondary analyses of RCTs, nonrandomised and non-English language studies. Duplicate screening for eligibility, risk of bias, and data extraction sample. Random effects meta-analysis. Statistical heterogeneity with inconsistency-value (I2). RESULTS: RCTs (n = 11) provided limited detail on target or achieved outdoor mobility intervention components. There was conflicting evidence from 2 RCTs for the effect on outdoor walking ability at 1-3 months (risk difference 0.19; 95% confidence intervals (CI): 0.21, 0.58; I2 = 92%), no effect on walking endurance at intervention end (standardised mean difference 0.05; 95% CI: - 0.26, 0.35; I2 = 36%); and suggestive (CI crosses null) of a small effect on self-efficacy at 1-3 months (standardised mean difference 0.25; 95% CI: - 0.29, 0.78; I2 = 87%) compared with routine care/sham intervention. CONCLUSION: It was not possible to attribute any benefit observed to an outdoor mobility intervention component due to poor reporting of target or achieved outdoor mobility and/or quality of the underlying evidence. Given the low proportion of patients recovering outdoor mobility after hip fracture, future research on interventions with outdoor mobility as a central component is warranted. TRIAL REGISTRATION: PROSPERO registration: CRD42021236541.

Items for consideration in a reporting guideline for mediation analyses: a Delphi study.

OBJECTIVES: Mediation analysis is a widely used quantitative method for investigating how interventions and exposures in randomised controlled trials and observational studies have an effect on healthcare outcomes. This study aimed to assess the importance of items that should be considered in a consensus meeting aimed at developing a guideline for reporting mediation analyses. DESIGN: International online Delphi study. PARTICIPANTS: International experts in the development and application of mediation analysis. MAIN OUTCOME MEASURES: The Delphi panel were asked to rate the importance of a list of items for inclusion in a guideline for reporting mediation analyses. Thresholds for disagreement and consensus on importance for inclusion were specified a priori. We used the Research ANd Development/University of California Los Angeles appropriateness method to quantitatively assess the importance for inclusion and panel agreement. RESULTS: Nineteen expert panellists (10 female) from seven countries agreed to participate. All panellists contributed to all three rounds conducted between 10 June 2019 and 6 November 2019. The panel reached consensus on 34 unique reporting items for study design, analytic procedures and effect estimates, with three items rated 'optional'. Panellists added one extra item and provided 60 qualitative comments for item refinement and prioritisation. CONCLUSION: This Delphi study used a rigorous consensus process to reach consensus on 34 reporting items for studies that use mediation analysis. These results will inform a consensus meeting that will consolidate a core set of recommended items for reporting mediation analyses.

Will We Do If We Can? Habitual Qualitative and Quantitative Physical Activity in Multi-Morbid, Older Persons with Cognitive Impairment.

This study aimed to identify determinants of quantitative dimensions of physical activity (PA; duration, frequency, and intensity) in community-dwelling, multi-morbid, older persons with cognitive impairment (CI). In addition, qualitative and quantitative aspects of habitual PA have been described. Quantitative PA and qualitative gait characteristics while walking straight and while walking turns were documented by a validated, sensor-based activity monitor. Univariate and multiple linear regression analyses were performed to delineate associations of quantitative PA dimensions with qualitative characteristics of gait performance and further potential influencing factors (motor capacity measures, demographic, and health-related parameters). In 94 multi-morbid, older adults (82.3 ± 5.9 years) with CI (Mini-Mental State Examination score: 23.3 ± 2.4), analyses of quantitative and qualitative PA documented highly inactive behavior (89.6% inactivity) and a high incidence of gait deficits, respectively. The multiple regression models (adjusted R2 = 0.395-0.679, all p < 0.001) identified specific qualitative gait characteristics as independent determinants for all quantitative PA dimensions, whereas motor capacity was an independent determinant only for the PA dimension duration. Demographic and health-related parameters were not identified as independent determinants. High associations between innovative, qualitative, and established, quantitative PA performances may suggest gait quality as a potential target to increase quantity of PA in multi-morbid, older persons.

Out-of-hours discharge from intensive care, in-hospital mortality and intensive care readmission rates: a systematic review and meta-analysis.

PURPOSE: Discharge from an intensive care unit (ICU) out of hours is common. We undertook a systematic review and meta-analysis to explore the association between time of discharge and mortality/ICU readmission. METHODS: We searched Medline, Embase, Web of Knowledge, CINAHL, the Cochrane Library and OpenGrey to June 2017. We included studies reporting in-hospital mortality and/or ICU readmission rates by ICU discharge "out-of-hours" and "in-hours". Inclusion was limited to patients aged ≥ 16 years discharged alive from a non-specialist ICU to a lower level of hospital care. Studies restricted to specific diseases were excluded. We assessed study quality using the Newcastle Ottowa Scale. We extracted published data, summarising using a random-effects meta-analysis. RESULTS: Our searches identified 1961 studies. We included unadjusted data from 1,191,178 patients from 18 cohort studies (presenting data from 1994 to 2014). "Out of hours" had multiple definitions, beginning between 16:00 and 22:00 and ending between 05:59 and 09:00. Patients discharged out of hours had higher in-hospital mortality [relative risk (95% CI) 1.39 (1.24, 1.57) p < 0.0001] and readmission rates [1·30 (1.19, 1.42), p < 0.001] than patients discharged in hours. Heterogeneity was high (I2 90.1% for mortality and 90.2% for readmission), resulting from differences in effect size rather than the presence of an effect. CONCLUSIONS: Out-of-hours discharge from an ICU is strongly associated with both in-hospital death and ICU readmission. These effects persisted across all definitions of "out of hours" and across healthcare systems in different geographical locations. Whether these increases in mortality and readmission result from patient differences, differences in care, or a combination remains unclear.

Development of a core outcome set for disease modification trials in mild to moderate dementia: a systematic review, patient and public consultation and consensus recommendations.

BACKGROUND: There is currently no disease-modifying treatment available to halt or delay the progression of the disease pathology in dementia. An agreed core set of the best-available and most appropriate outcomes for disease modification would facilitate the design of trials and ensure consistency across disease modification trials, as well as making results comparable and meta-analysable in future trials. OBJECTIVES: To agree a set of core outcomes for disease modification trials for mild to moderate dementia with the UK dementia research community and patient and public involvement (PPI). DATA SOURCES: We included disease modification trials with quantitative outcomes of efficacy from (1) references from related systematic reviews in workstream 1; (2) searches of the Cochrane Dementia and Cognitive Improvement Group study register, Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature, EMBASE, Latin American and Caribbean Health Sciences Literature and PsycINFO on 11 December 2015, and clinical trial registries [International Standard Randomised Controlled Trial Number (ISRCTN) and clinicaltrials.gov] on 22 and 29 January 2016; and (3) hand-searches of reference lists of relevant systematic reviews from database searches. REVIEW METHODS: The project consisted of four workstreams. (1) We obtained related core outcome sets and work from co-applicants. (2) We systematically reviewed published and ongoing disease modification trials to identify the outcomes used in different domains. We extracted outcomes used in each trial, recording how many used each outcome and with how many participants. We divided outcomes into the domains measured and searched for validation data. (3) We consulted with PPI participants about recommended outcomes. (4) We presented all the synthesised information at a conference attended by the wider body of National Institute for Health Research (NIHR) dementia researchers to reach consensus on a core set of outcomes. RESULTS: We included 149 papers from the 22,918 papers screened, referring to 125 individual trials. Eighty-one outcomes were used across trials, including 72 scales [31 cognitive, 12 activities of daily living (ADLs), 10 global, 16 neuropsychiatric and three quality of life] and nine biological techniques. We consulted with 18 people for PPI. The conference decided that only cognition and biological markers are core measures of disease modification. Cognition should be measured by the Mini Mental State Examination (MMSE) or the Alzheimer's Disease Assessment Scale - Cognitive subscale (ADAS-Cog), and brain changes through structural magnetic resonance imaging (MRI) in a subset of participants. All other domains are important but not core. We recommend using the Neuropsychiatric Inventory for neuropsychiatric symptoms: the Disability Assessment for Dementia for ADLs, the Dementia Quality of Life Measure for quality of life and the Clinical Dementia Rating scale to measure dementia globally. LIMITATIONS: Most of the trials included participants with Alzheimer's disease, so recommendations may not apply to other types of dementia. We did not conduct economic analyses. The PPI consultation was limited to members of the Alzheimer's Society Research Network. CONCLUSIONS: Cognitive outcomes and biological markers form the core outcome set for future disease modification trials, measured by the MMSE or ADAS-Cog, and structural MRI in a subset of participants. FUTURE WORK: We envisage that the core set may be superseded in the future, particularly for other types of dementia. There is a need to develop an algorithm to compare scores on the MMSE and ADAS-Cog. STUDY REGISTRATION: The project was registered with Core Outcome Measures in Effectiveness Trials [ www.comet-initiative.org/studies/details/819?result=true (accessed 7 April 2016)]. The systematic review protocol is registered as PROSPERO CRD42015027346. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

A randomised controlled trial and cost-effectiveness analysis of high-frequency oscillatory ventilation against conventional artificial ventilation for adults with acute respiratory distress syndrome. The OSCAR (OSCillation in ARDS) study.

BACKGROUND: Patients with the acute respiratory distress syndrome (ARDS) require artificial ventilation but this treatment may produce secondary lung damage. High-frequency oscillatory ventilation (HFOV) may reduce this damage. OBJECTIVES: To determine the clinical benefit and cost-effectiveness of HFOV in patients with ARDS compared with standard mechanical ventilation. DESIGN: A parallel, randomised, unblinded clinical trial. SETTING: UK intensive care units. PARTICIPANTS: Mechanically ventilated patients with a partial pressure of oxygen in arterial blood/fractional concentration of inspired oxygen (P : F) ratio of 26.7 kPa (200 mmHg) or less and an expected duration of ventilation of at least 2 days at recruitment. INTERVENTIONS: Treatment arm HFOV using a Novalung R100(®) ventilator (Metran Co. Ltd, Saitama, Japan) ventilator until the start of weaning. Control arm Conventional mechanical ventilation using the devices available in the participating centres. MAIN OUTCOME MEASURES: The primary clinical outcome was all-cause mortality at 30 days after randomisation. The primary health economic outcome was the cost per quality-adjusted life-year (QALY) gained. RESULTS: One hundred and sixty-six of 398 patients (41.7%) randomised to the HFOV group and 163 of 397 patients (41.1%) randomised to the conventional mechanical ventilation group died within 30 days of randomisation (p = 0.85), for an absolute difference of 0.6% [95% confidence interval (CI) -6.1% to 7.5%]. After adjustment for study centre, sex, Acute Physiology and Chronic Health Evaluation II score, and the initial P : F ratio, the odds ratio for survival in the conventional ventilation group was 1.03 (95% CI 0.75 to 1.40; p = 0.87 logistic regression). Survival analysis showed no difference in the probability of survival up to 12 months after randomisation. The average QALY at 1 year in the HFOV group was 0.302 compared to 0.246. This gives an incremental cost-effectiveness ratio (ICER) for the cost to society per QALY of £88,790 and an ICER for the cost to the NHS per QALY of £ 78,260. CONCLUSIONS: The use of HFOV had no effect on 30-day mortality in adult patients undergoing mechanical ventilation for ARDS and no economic advantage. We suggest that further research into avoiding ventilator-induced lung injury should concentrate on ventilatory strategies other than HFOV. TRIAL REGISTRATION: Current Controlled Trials ISRCTN10416500.

Physiotherapy Rehabilitation for Osteoporotic Vertebral Fracture (PROVE): study protocol for a randomised controlled trial.

BACKGROUND: Osteoporosis and vertebral fracture can have a considerable impact on an individual's quality of life. There is increasing evidence that physiotherapy including manual techniques and exercise interventions may have an important treatment role. This pragmatic randomised controlled trial will investigate the clinical and cost-effectiveness of two different physiotherapy approaches for people with osteoporosis and vertebral fracture, in comparison to usual care. METHODS/DESIGN: Six hundred people with osteoporosis and a clinically diagnosed vertebral fracture will be recruited and randomly allocated to one of three management strategies, usual care (control - A), an exercise-based physiotherapy intervention (B) or a manual therapy-based physiotherapy intervention (C). Those in the usual care arm will receive a single session of education and advice, those in the active treatment arms (B + C) will be offered seven individual physiotherapy sessions over 12 weeks. The trial is designed as a prospective, adaptive single-blinded randomised controlled trial. An interim analysis will be completed and if one intervention is clearly superior the trial will be adapted at this point to continue with just one intervention and the control. The primary outcomes are quality of life measured by the disease specific QUALLEFO 41 and the Timed Loaded Standing test measured at 1 year. DISCUSSION: There are a variety of different physiotherapy packages used to treat patients with osteoporotic vertebral fracture. At present, the indication for each different therapy is not well defined, and the effectiveness of different modalities is unknown. TRIAL REGISTRATION: Reference number ISRCTN49117867.

The administration of intermittent parathyroid hormone affects functional recovery from pertrochanteric fractured neck of femur: a protocol for a prospective mixed method pilot study with randomisation of treatment allocation and blinded assessment (FRACTT).

INTRODUCTION: Pertrochanteric hip fractures occur in an elderly population and cause considerable morbidity and loss of functional ability as the fracture heals. Recently, parathyroid hormone (PTH), which is licensed for the treatment of osteoporosis, has been shown to potentially accelerate bone healing in animal and human studies. If its administration could allow a faster functional recovery after pertrochanteric hip fracture, then a patient's hospital stay may be reduced and rehabilitation could be potentially accelerated. PTH can currently only be administered by subcutaneous injection. The acceptability of this intervention is unknown in this elderly population. The aim of this pilot study is to inform the design of a future powered study comparing the functional recovery after pertrochanteric hip fracture in patients undergoing standard care versus those who undergo administration of subcutaneous injection of PTH. METHODS AND ANALYSIS: The study is an open label, prospective, randomised, comparative pilot study with blinded outcomes assessment to establish feasibility of the trial design. Patients will be randomised to receive a 6-week course of PTH or usual treatment. Functional outcomes will be assessed at 6 weeks and 12 weeks. Blinded assessment will be used to minimise the effect of bias of an open label study design. A nested qualitative study will investigate the patient experience of, and expectations following, hip fracture and the patient important aspects of recovery compared with the outcome measures proposed. RESULTS: Results will be analysed to establish the potential recruitment, compliance and retention rates using 95% CIs, and trial outcomes quoted with SDs and 95% CIs for the effect size. ETHICS AND DISSEMINATION: The study has been approved by the South West 2 Research Ethics committee (reference 10/H0206/34). The findings of this study will be disseminated to the medical community via presentations to orthopaedic, orthogeriatric and osteoporosis societies, and their relevant specialist journals. TRIAL REGISTRATION: ISRCTN Register reference number: ISRCTN03362357. Eudract Number: 2010-020081-22.