Evaluating an extended rehabilitation service for stroke patients (EXTRAS): Study protocol for a randomised controlled trial

Background: Development of longer term stroke rehabilitation services is limited by lack of evidence of effectiveness for specific interventions and service models. We describe the protocol for a multicentre randomised controlled trial which is evaluating an extended stroke rehabilitation service. The extended service commences when routine 'organised stroke care' (stroke unit and early supported discharge (ESD)) ends. Methods/design: This study is a multicentre randomised controlled trial with health economic and process evaluations. It is set within NHS stroke services which provide ESD. Participants are adults who have experienced a new stroke (and carer if appropriate), discharged from hospital under the care of an ESD team. Discussion: The provision of longer term support for stroke survivors is currently limited. The results from this trial will inform future stroke service planning and configuration. Trial registration: This trial was registered with ISRCTN (identifier: ISRCTN45203373) on 9 August 2012

Developing an intervention for fall-related injuries in dementia (DIFRID): an integrated, mixed-methods approach

This is the final version. Available on open access from BMC via the DOI in this recordThe datasets generated during and/or analysed during the current study are available from the corresponding author (LA) on reasonable request. The data are not publicly available due to them containing information that could compromise research participant confidentialityBackground: Falls in people with dementia can result in a number of physical and psychosocial consequences. However, there is limited evidence to inform how best to deliver services to people with dementia following a fall. The aim of the DIFRID study was to determine the feasibility of developing and implementing a new intervention to improve outcomes for people with dementia with fall-related injuries; this encompasses both short-term recovery and reducing the likelihood of future falls. This paper details the development of the DIFRID intervention. Methods: The intervention was designed using an integrated, mixed-methods approach. This involved a realist synthesis of the literature and qualitative data gathered through interviews and focus groups with health and social care professionals (n=81). An effectiveness review and further interviews and observation were also conducted and are reported elsewhere. A modified Delphi panel approach with 24 experts was then used to establish a consensus on how the findings should translate into a new intervention. After feedback from key stakeholders (n=15) on the proposed model, the intervention was manualised and training developed. Results: We identified key components of a new intervention covering three broad areas: • Ensuring that the circumstances of rehabilitation are optimised for people with dementia • Compensating for the reduced ability of people with dementia to self-manage • Equipping the workforce with the necessary skills and information to care for this patient group Consensus was achieved on 54 of 69 statements over two rounds of the Delphi surveys. The statements were used to model the intervention and finalise the accompanying manual and protocol for a feasibility study. Stakeholder feedback was generally positive and the majority of suggested intervention components were approved. The proposed outcome was a 12-week complex multidisciplinary intervention primarily based at the patient’s home. Conclusions: A new intervention has been developed to improve outcomes for people with dementia following a fall requiring healthcare attention. The feasibility of this intervention is currently being tested.National Institute for Health Research (NIHR

An intervention to improve outcomes of falls in dementia: the DIFRID mixed-methods feasibility study:A mixed methods study to develop and assess the feasibility of the DIFRID intervention

Background : Fall-related injuries are a significant cause of morbidity and mortality in people with dementia (PWD). There is presently little evidence to guide the management of such injuries, and yet there are potentially substantial benefits to be gained if the outcome of these injuries could be improved. This study aimed to design an appropriate new healthcare intervention for PWD following a fall and to assess the feasibility of its delivery in the UK National Health Service. Objective (s): To determine whether it is possible to design an intervention to improve outcomes of falls in dementia; to investigate the feasibility and acceptability of the DIFRID intervention; to investigate the feasibility of a future randomised controlled trial (RCT) and data collection tools needed to evaluate the effectiveness and efficiency of the DIFRID intervention. Design : Mixed-methods feasibility study. Methods : A systematic review (using Cochrane methodology) and realist review (using RAMESES methodology) explored the existing evidence base and developed programme theories. Searches were carried out in Nov 2015 (updated Jan 2018) for effectiveness studies and August 2016 for economic studies. A prospective observational study identified service use via participant diary completion. Qualitative methods (semi-structured interviews, focus groups, and observation) were used to explore: current practice; stakeholder perspectives of the health and social care needs of PWD following a fall; ideas for intervention; and barriers and facilitators to change. Each of these datasets informed intervention development, via Delphi consensus methods. Finally, a single-arm feasibility study with embedded process evaluation was conducted. Setting : Community. Participants : PWD presenting with falls needing healthcare attention in each setting at 3 sites and their carers. Professionals delivering the intervention, responsible for training and supervision and members of the intervention team. Professionals responsible for approaching and recruiting participants. Interventions: A complex multidisciplinary therapy intervention. Physiotherapists, occupational therapists, and support workers delivered up to 22 sessions of tailored activities in the PWD’s home or local area over a period of 12 weeks. Main outcome measures: Assessment of feasibility of study procedures; assessment of the acceptability, feasibility and fidelity of intervention components; assessment of suitability and acceptability of outcome measures for PWD and carers (number of falls; quality of life; fear of falling; activities of daily living; goal setting; health utilisation; carer burden). Results : A multidisciplinary intervention delivered in PWDs’ own homes was designed based on qualitative work, realist review and recommendations of the consensus panel. The intervention was delivered to 11 PWD. The study suggested that the intervention is both feasible and acceptable to stakeholders. A number of modifications was recommended to address some of the issues arising during feasibility testing. Measurement of outcome measures was successful. Limitations : Recruitment to the feasibility study was lower than expected and therefore the intervention needs to be tested with a larger number of PWD. Conclusions : The study has highlighted the feasibility of delivering a creative, tailored, individual approach to intervention for PWD following a fall. Although the intervention required greater investment of time than usual practice, many staff valued the opportunity to work more closely with PWD and carers. Future work : We conclude that further research is now needed to refine this intervention in the context of a pilot randomised controlled trial

Nasal Airway Obstruction Study (NAIROS): a phase III, open-label, mixed-methods, multicentre randomised controlled trial of septoplasty versus medical management of a septal deviation with nasal obstruction

Background Septoplasty (surgery to straighten a deviation in the nasal septum) is a frequently performed operation worldwide, with approximately 250,000 performed annually in the US and 22,000 in the UK. Most septoplasties aim to improve diurnal and nocturnal nasal obstruction. The evidence base for septoplasty clinical effectiveness is hitherto very limited. Aims To establish, and inform guidance for, the best management strategy for individuals with nasal obstruction associated with a deviated septum. Methods/design A multicentre, mixed-methods, open label, randomised controlled trial of septoplasty versus medical management for adults with a deviated septum and a reduced nasal airway. Eligible patients will have septal deflection visible at nasendoscopy and a nasal symptom score ≥ 30 on the NOSE questionnaire. Surgical treatment comprises septoplasty with or without reduction of the inferior nasal turbinate on the anatomically wider side of the nose. Medical management comprises a nasal saline spray followed by a fluorinated steroid spray daily for six months. The recruitment target is 378 patients, recruited from up to 17 sites across Scotland, England and Wales. Randomisation will be on a 1:1 basis, stratified by gender and severity (NOSE score). Participants will be followed up for 12 months post randomisation. The primary outcome measure is the total SNOT-22 score at 6 months. Clinical and economic outcomes will be modelled against baseline severity (NOSE scale) to inform clinical decision-making. The study includes a recruitment enhancement process, and an economic evaluation. Discussion The NAIROS trial will evaluate the clinical effectiveness and cost-effectiveness of septoplasty versus medical management for adults with a deviated septum and symptoms of nasal blockage. Identifying those individuals most likely to benefit from surgery should enable more efficient and effective clinical decision-making, and avoid unnecessary operations where there is low likelihood of patient benefit

Second primary cancer risk - the impact of applying different definitions of multiple primaries: results from a retrospective population-based cancer registry study

Background: There is evidence that cancer survivors are at increased risk of second primary cancers. Changes in the prevalence of risk factors and diagnostic techniques may have affected more recent risks.<p></p> Methods: We examined the incidence of second primary cancer among adults in the West of Scotland, UK, diagnosed with cancer between 2000 and 2004 (n = 57,393). We used National Cancer Institute Surveillance Epidemiology and End Results and International Agency for Research on Cancer definitions of multiple primary cancers and estimated indirectly standardised incidence ratios (SIR) with 95% confidence intervals (CI).<p></p> Results: There was a high incidence of cancer during the first 60 days following diagnosis (SIR = 2.36, 95% CI = 2.12 to 2.63). When this period was excluded the risk was not raised, but it was high for some patient groups; in particular women aged <50 years with breast cancer (SIR = 2.13, 95% CI = 1.58 to 2.78), patients with bladder (SIR = 1.41, 95% CI = 1.19 to 1.67) and head & neck (SIR = 1.93, 95% CI = 1.67 to 2.21) cancer. Head & neck cancer patients had increased risks of lung cancer (SIR = 3.75, 95% CI = 3.01 to 4.62), oesophageal (SIR = 4.62, 95% CI = 2.73 to 7.29) and other head & neck tumours (SIR = 6.10, 95% CI = 4.17 to 8.61). Patients with bladder cancer had raised risks of lung (SIR = 2.18, 95% CI = 1.62 to 2.88) and prostate (SIR = 2.41, 95% CI = 1.72 to 3.30) cancer.<p></p> Conclusions: Relative risks of second primary cancers may be smaller than previously reported. Premenopausal women with breast cancer and patients with malignant melanomas, bladder and head & neck cancers may benefit from increased surveillance and advice to avoid known risk factors

Rhomboid family member 2 regulates cytoskeletal stress-associated Keratin 16.

Keratin 16 (K16) is a cytoskeletal scaffolding protein highly expressed at pressure-bearing sites of the mammalian footpad. It can be induced in hyperproliferative states such as wound healing, inflammation and cancer. Here we show that the inactive rhomboid protease RHBDF2 (iRHOM2) regulates thickening of the footpad epidermis through its interaction with K16. K16 expression is absent in the thinned footpads of irhom2-/- mice compared with irhom2+/+mice, due to reduced keratinocyte proliferation. Gain-of-function mutations in iRHOM2 underlie Tylosis with oesophageal cancer (TOC), characterized by palmoplantar thickening, upregulate K16 with robust downregulation of its type II keratin binding partner, K6. By orchestrating the remodelling and turnover of K16, and uncoupling it from K6, iRHOM2 regulates the epithelial response to physical stress. These findings contribute to our understanding of the molecular mechanisms underlying hyperproliferation of the palmoplantar epidermis in both physiological and disease states, and how this 'stress' keratin is regulated

Search for Fractional Charges Produced in Heavy-Ion Collisions at 1.9 GeV/nucleon

An experiment was performed to capture fractionally charged particles produced in heavy-ion collisions and to concentrate them in samples suitable for analysis by various techniques. Two of the samples so produced have been searched, with use of an automated version of Millikan\u27s oil-drop apparatus. The beam was 56Fe at 1.9 GeV/nucleon, incident on a lead target. Less than one fractional charge per 1.0× 104 Fe-Pb collisions was found to be produced, and, with further assumptions, less than one per 2.0× 106 collisions

Evaluation of an Extended Stroke Rehabilitation Service (EXTRAS): A Randomized Controlled Trial and Economic Analysis

Background and Purpose— There is limited evidence to guide rehabilitation to meet the longer term needs of stroke survivors. The clinical effectiveness and cost-effectiveness of an extended stroke rehabilitation service (EXTRAS) provided following early supported discharge were determined. Methods— EXTRAS was a pragmatic parallel-group observer-blind randomized controlled trial involving 19 UK centers. Patients with stroke were individually randomized to receive EXTRAS or usual care at discharge from early supported discharge. Five EXTRAS reviews were provided by an early supported discharge team member between one and 18 months, usually by telephone. Reviews consisted of a semi-structured interview assessing progress, rehabilitation needs, and service provision, with goal setting and action planning. The primary outcome was performance in extended activities of daily living (Nottingham EADL Scale) at 24 months post-randomization. The Nottingham EADL Scale is scored 0 to 66, with higher scores indicating better performance in these activities. Cost-effectiveness was estimated using resource utilization costs and Quality Adjusted Life Years. Analyses were intention to treat. Results— Between January 9, 2013 and October 26, 2015, 573 participants were randomized (EXTRAS, n=285; usual care, n=288). Mean 24 month Nottingham EADL Scale scores were EXTRAS (n=219) 40.0 (SD 18.1) and usual care (n=231) 37.2 (SD 18.5) giving an adjusted mean difference of 1.8 (95% CI, –0.7 to 4.2). 1155/1338 (86%) of expected EXTRAS reviews were undertaken. Over 24 months, the mean cost of resource utilization was lower in the intervention group: –£311 (–$450 [95$4764 to $4033]). EXTRAS provided more Quality Adjusted Life Years (0.07 [95$28 940] per Quality Adjusted Life Years), there was a 90% chance that EXTRAS could be considered cost-effective. Conclusions— EXTRAS did not significantly improve stroke survivors’ performance in extended activities of daily living. However, given the impact on costs and Quality Adjusted Life Years, EXTRAS may be an affordable addition to improve stroke care

Robot-assisted training compared with an enhanced upper limb therapy programme and with usual care for upper limb functional limitation after stroke: the RATULS three-group RCT

Background Loss of arm function is common after stroke. Robot-assisted training may improve arm outcomes. Objective The objectives were to determine the clinical effectiveness and cost-effectiveness of robot-assisted training, compared with an enhanced upper limb therapy programme and with usual care. Design This was a pragmatic, observer-blind, multicentre randomised controlled trial with embedded health economic and process evaluations. Setting The trial was set in four NHS trial centres. Participants Patients with moderate or severe upper limb functional limitation, between 1 week and 5 years following first stroke, were recruited. Interventions Robot-assisted training using the Massachusetts Institute of Technology-Manus robotic gym system (InMotion commercial version, Interactive Motion Technologies, Inc., Watertown, MA, USA), an enhanced upper limb therapy programme comprising repetitive functional task practice, and usual care. Main outcome measures The primary outcome was upper limb functional recovery ‘success’ (assessed using the Action Research Arm Test) at 3 months. Secondary outcomes at 3 and 6 months were the Action Research Arm Test results, upper limb impairment (measured using the Fugl-Meyer Assessment), activities of daily living (measured using the Barthel Activities of Daily Living Index), quality of life (measured using the Stroke Impact Scale), resource use costs and quality-adjusted life-years. Results A total of 770 participants were randomised (robot-assisted training, n = 257; enhanced upper limb therapy, n = 259; usual care, n = 254). Upper limb functional recovery ‘success’ was achieved in the robot-assisted training [103/232 (44%)], enhanced upper limb therapy [118/234 (50%)] and usual care groups [85/203 (42%)]. These differences were not statistically significant; the adjusted odds ratios were as follows: robot-assisted training versus usual care, 1.2 (98.33% confidence interval 0.7 to 2.0); enhanced upper limb therapy versus usual care, 1.5 (98.33% confidence interval 0.9 to 2.5); and robot-assisted training versus enhanced upper limb therapy, 0.8 (98.33% confidence interval 0.5 to 1.3). The robot-assisted training group had less upper limb impairment (as measured by the Fugl-Meyer Assessment motor subscale) than the usual care group at 3 and 6 months. The enhanced upper limb therapy group had less upper limb impairment (as measured by the Fugl-Meyer Assessment motor subscale), better mobility (as measured by the Stroke Impact Scale mobility domain) and better performance in activities of daily living (as measured by the Stroke Impact Scale activities of daily living domain) than the usual care group, at 3 months. The robot-assisted training group performed less well in activities of daily living (as measured by the Stroke Impact Scale activities of daily living domain) than the enhanced upper limb therapy group at 3 months. No other differences were clinically important and statistically significant. Participants found the robot-assisted training and the enhanced upper limb therapy group programmes acceptable. Neither intervention, as provided in this trial, was cost-effective at current National Institute for Health and Care Excellence willingness-to-pay thresholds for a quality-adjusted life-year. Conclusions Robot-assisted training did not improve upper limb function compared with usual care. Although robot-assisted training improved upper limb impairment, this did not translate into improvements in other outcomes. Enhanced upper limb therapy resulted in potentially important improvements on upper limb impairment, in performance of activities of daily living, and in mobility. Neither intervention was cost-effective. Future work Further research is needed to find ways to translate the improvements in upper limb impairment seen with robot-assisted training into improvements in upper limb function and activities of daily living. Innovations to make rehabilitation programmes more cost-effective are required. Limitations Pragmatic inclusion criteria led to the recruitment of some participants with little prospect of recovery. The attrition rate was higher in the usual care group than in the robot-assisted training or enhanced upper limb therapy groups, and differential attrition is a potential source of bias. Obtaining accurate information about the usual care that participants were receiving was a challenge. Trial registration Current Controlled Trials ISRCTN69371850. 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. 24, No. 54. See the NIHR Journals Library website for further project information