BACKGROUND: the aim of fistula surgery is to eradicate the disease while preserving anal sphincter function. The efficacy of the Surgisis® anal fistula plug (Cook Medical, Bloomington, IN, USA) in the treatment of trans-sphincteric fistula-in-ano has been variably reported. OBJECTIVES: to undertake a randomised comparison of the safety and efficacy of the Surgisis anal fistula plug in comparison with surgeon's preference for the treatment of trans-sphincteric anal fistulas. DESIGN: a randomised, unblinded, parallel-arm, prospective, multicentre clinical trial. SETTING: Hospitals in the UK NHS involving colorectal surgeons accredited by the Association of Coloproctology of Great Britain and Ireland. PARTICIPANTS: Adult patients suffering from trans-sphincteric fistula-in-ano of cryptoglandular origin. INTERVENTIONS: Patients were randomised on a 1 : 1 basis to either the fistula plug or the surgeon's preference [e.g. fistulotomy, cutting seton, advancement flap or ligation of intersphincteric fistula tract (LIFT) procedure]. MAIN OUTCOME MEASURES: the primary outcome measure was quality of life as measured by the Faecal Incontinence Quality of Life (FIQoL) questionnaire at 12-month follow-up. Secondary outcome measures included clinical and radiological fistula healing rates, faecal incontinence rates, complications rates, reintervention rates and cost-effectiveness. RESULTS: Between May 2011 and March 2016, 304 participants were recruited (152 fistula plug vs. 152 surgeon's preference). No difference in FIQoL score between the two trial groups was seen at the 6-week, 6-month or 12-month follow-up. Clinical evidence of fistula healing was reported in 66 of 122 (54%) participants in the fistula plug group and in 66 of 119 (55%) participants in the surgeon's preference group at 12 months. Magnetic resonance imaging (MRI) showed fistula healing in 54 of 110 (49%) participants in the fistula plug group and in 63 of 112 (56%) participants in the surgeon's preference group. Variation in 12-month clinical healing rates was observed: 55%, 64%, 75%, 53% and 42% for fistula plug, cutting seton, fistulotomy, advancement flap and LIFT procedure, respectively. Faecal incontinence rates were low at baseline, with small improvement in both groups post treatment. Complications and reinterventions were frequent. The mean total costs were £2738 [standard deviation (SD) £1151] in the fistula plug group and £2308 (SD £1228) in the surgeon's preference group. The average total quality-adjusted life-years (QALYs) gain was much smaller in the fistula plug group (0.829, SD 0.174) than in the surgeon's preference group (0.790, SD 0.212). Using multiple imputation and probabilistic sensitivity analysis, and adjusting for differences in baseline EuroQol-5 Dimensions, three-level version utility, there was a 35-45% chance that the fistula plug was as cost-effective as surgeon's preference over a range of thresholds of willingness to pay for a single QALY of £20,000-30,000. LIMITATIONS: Limitations include a smaller sample size than originally calculated, a lack of blinding that perhaps biased patient-reported outcomes and a lower compliance rate with MRI at 12-month follow-up. CONCLUSIONS: the Surgisis anal fistula plug is associated with similar FIQoL score to surgeon's preference at 12-month follow-up. The higher costs and highly uncertain and small gains in QALYs associated with the fistula plug mean that this technology is unlikely to be considered a cost-effective use of resources in the UK NHS. FUTURE WORK: Further in-depth analysis should consider the clinical and MRI characteristics of fistula-in-ano in an attempt to identify predictors of fistula response to treatment. TRIAL REGISTRATION: Current Controlled Trials ISRCTN78352529. 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. 23, No. 21. See the NIHR Journals Library website for further project information.

© 2018 the Authors Background and Objectives: Prospective, monthly diaries are recommended for collecting falls data but are burdensome and expensive. The aim of the article was to compare characteristics of fallers and estimates of fall rates by method of data collection. Study Design and Setting: a methodology study nested within a large cluster randomized controlled trial. We randomized 9,803 older adults from 63 general practices across England to receive one of three fall prevention interventions. Participants provided a retrospective report of falls in postal questionnaires mailed every 4 months. A separate randomization allocated participants to receive prospective monthly falls diaries for one simultaneous 4-month period. Results: Falls diaries were returned by 7,762 of 9,375 (83%); of which 6,306 (67%) participants reported the same number of falls on both data sources. Diary nonresponders were older and had poorer levels of physical and mental health. Analysis of time points where both data sources were available showed the falls rate on diaries was consistently higher than on the questionnaire (mean rate: 0.16 vs. 0.12 falls per person-month observation). Diary allocation was associated with a higher rate of withdrawal from the main trial. Conclusion: Diary completion was associated with sample attrition. We found on average a 32% difference in falls rates between the two data sources. Retrospective and prospective falls data are not consistently reported when collected simultaneously.

OBJECTIVE: Long-term issues following diagnosis and treatment of a childhood brain tumour often become apparent as the survivor enters adolescence and young adulthood. Their caregivers may additionally face long-term impacts on their emotional and psychological functioning. This review synthesised evidence on the issues and supportive care needs of adolescent and young adult (AYA) survivors of a brain tumour diagnosed in childhood and their caregivers. METHODS: Electronic databases were searched up until September 2017. All studies reporting on issues or needs of childhood brain tumour survivors (aged 14-39) and their caregivers were included. Narrative synthesis methods were used to summarise, integrate, and interpret findings. RESULTS: Fifty-six articles (49 studies) met the inclusion criteria. Social issues (ie, isolation and impaired daily functioning) were most commonly reported by survivors, followed by cognitive (ie, impaired memory and attention) and physical issues (ie, endocrine dysfunctions and fatigue). Survivors experienced poorer social functioning and sexual functioning and were less likely to be employed or have children, when compared with other AYA cancer survivors. Caregivers experienced reduced support as the survivor moved into young adulthood. Caregivers reported uncertainty, increased responsibilities, and problems maintaining their own self-well-being and family relationships. Few studies reported on supportive care needs. Survivors expressed a need for better educational support and age-specific psychosocial services. CONCLUSIONS: Surviving a childhood brain tumour can be particularly challenging for AYA survivors and their caregivers. Robust structured research is needed to identify specific support needs of both survivors and their caregivers and how these can be optimally addressed.

© 2018 the Authors Objective: to evaluate the impact of the QuinteT Recruitment Intervention (QRI) on recruitment in challenging randomized controlled trials (RCTs) that have applied the intervention. The QRI aims to understand recruitment difficulties and then implements “QRI actions” to address these as recruitment proceeds. Study Design and Setting: a mixed-methods study, comprising (1) before-and-after comparisons of recruitment rates and the numbers of patients approached and (2) qualitative case studies, including documentary analysis and interviews with RCT investigators. Results: Five UK-based publicly funded RCTs were included in the evaluation. All recruited to target. Randomized controlled trial 2 and RCT 5 both received up-front prerecruitment training before the intervention was applied. Randomized controlled trial 2 did not encounter recruitment issues and recruited above target from its outset. Recruitment difficulties, particularly communication issues, were identified and addressed through QRI actions in RCTs 1, 3, 4, and 5. Randomization rates significantly improved after QRI action in RCTs 1, 3, and 4. Quintet Recruitment Intervention actions addressed issues with approaching eligible patients in RCTs 3 and 5, which both saw significant increases in the number of patients approached. Trial investigators reported that the QRI had unearthed issues they had been unaware of and reportedly changed their practices after QRI action. Conclusion: There is promising evidence to suggest that the QRI can support recruitment to difficult RCTs. This needs to be substantiated with future controlled evaluations.

PURPOSE: the Weight-specific Adolescent Instrument for Economic evaluation (WAItE) is a 7-item condition-specific tool assessing the impact of weight status on seven dimensions of quality of life. The content of the WAItE was developed with both treatment-seeking and non-treatment-seeking adolescents aged 11-18 years. The aim of this study was to assess the psychometric properties of the WAItE in adolescent and adult populations. METHODS: Treatment-seeking adolescents with obesity (females n = 155; males n = 123; mean age = 13.3; 13.1 years, respectively) completed the WAItE twice. An adult general population sample completed the WAItE via an online survey (females n = 236; males n = 231; mean age = 41.2; 44.3 years, respectively). The Partial Credit Model was applied to the data and item fit evaluated against published criteria. RESULTS: the WAItE had a unidimensional structure both for adolescents and adults. There was no item misfit observed for either participant samples and no differential item functioning (DIF) was present by age or gender for the adolescents. Some DIF was observed across age groups for the adult sample. For the adolescent sample, stable item locations were observed over time. CONCLUSIONS: the aim of the WAItE is to assess the impact of weight status on the lives of adolescents in cost-effectiveness evaluation of weight management programmes. The results of this study demonstrated that the WAItE has reliable psychometric properties. The instrument may therefore be used to aid informed decision around the identification of cost-effective weight management programmes in both adolescent and adult populations.

BACKGROUND: National guidelines (NICE-CG175) recommended 12 weeks of supervised exercise training for men treated with androgen deprivation therapy (ADT) for prostate cancer to counter debilitating adverse effects of castration. As with other chronic conditions where exercise is indicated, it is uncertain if these services are being delivered in the health services. The aim of this multi-centre investigation was to examine what exercise referral is currently available for men on ADT as provided by the NHS and if a supervised, individually-tailored exercise training package (as per the national NICE guidelines CG175) is embedded within prostate cancer care. METHODS: a multi-centre investigation of current National Health Service (NHS) care involving a web-based survey of NHS prostate cancer care, five focus groups involving 26 men on ADT and 37 semi-structured interviews with healthcare professionals (HCPs) involved in the management of prostate cancer. Descriptive statistics and thematic analysis evaluated quantitative and qualitative data, respectively. Qualitative methods followed COREQ standards. RESULTS: HCPs and men on ADT asserted that medical castration has a serious and debilitating impact on many features of men's quality of life. There is support for exercise training programmes as part of cancer care and patients would support their initiation soon after diagnosis. Involving the Multidisciplinary Team (MDT) is proposed as key to this. Critically, traditional values in oncology would need to be overcome for widespread acceptance. Specialist further training for HCPs around behaviour change support could encourage this. Given that these schemes are seen as a fundamental part of cancer care, it is felt the NHS should commission and support provision. 79 representatives of 154 NHS trusts (51%) provided survey data on current delivery: only 17% could provide supervised exercise as per CG175. CONCLUSIONS: Evidence-based national exercise guidelines are not being delivered to men on ADT as intended. Traditional values in oncology and the need for NHS financial support are seen as major barriers to provision of current best practice guidelines. Despite this both HCPs and men on ADT are in favour of such programmes being a fundamental part of their cancer care.

© 2018 the Author(s). Background: Mechanisms by which liaison mental health services (LMHS) may bring about improved patient and organisational outcomes are poorly understood. A small number of logic models have been developed, but they fail to capture the complexity of clinical practice. Method: We synthesised data from a variety of sources including a large national survey, 73 in-depth interviews with acute and liaison staff working in hospitals with different types of liaison mental health services, and relevant local, national and international literature. We generated logic models for two common performance indicators used to assess organisational outcomes for LMHS: response times in the emergency department and hospital length of stay for people with mental health problems. Results: We identified 8 areas of complexity that influence performance, and 6 trade-offs which drove the models in different directions depending upon the balance of the trade-off. The logic models we developed could only be captured by consideration of more than one pass through the system, the complexity in which they operated, and the trade-offs that occurred. Conclusions: Our findings are important for commissioners of liaison services. Reliance on simple target setting may result in services that are unbalanced and not patient-centred. Targets need to be reviewed on a regular basis, together with other data that reflect the wider impact of the service, and any external changes in the system that affect the performance of LMHS, which are beyond their control.

© 2018 University of Bristol Objectives: to explore how the concept of randomization is described by clinicians and understood by patients in randomized controlled trials (RCTs) and how it contributes to patient understanding and recruitment. Study Design and Setting: Qualitative analysis of 73 audio recordings of recruitment consultations from five, multicenter, UK-based RCTs with identified or anticipated recruitment difficulties. Results: One in 10 appointments did not include any mention of randomization. Most included a description of the method or process of allocation. Descriptions often made reference to gambling-related metaphors or similes, or referred to allocation by a computer. Where reference was made to a computer, some patients assumed that they would receive the treatment that was “best for them”. Descriptions of the rationale for randomization were rarely present and often only came about as a consequence of patients questioning the reason for a random allocation. Conclusions: the methods and processes of randomization were usually described by recruiters, but often without clarity, which could lead to patient misunderstanding. The rationale for randomization was rarely mentioned. Recruiters should avoid problematic gambling metaphors and illusions of agency in their explanations and instead focus on clearer descriptions of the rationale and method of randomization to ensure patients are better informed about randomization and RCT participation.

© 2018 John Wiley. &. Sons Ltd Background: We developed a multifaceted intervention to reduce antibiotic prescription rate for children with upper respiratory tract infections (URTIs) among primary care doctors in township hospitals in China. The intervention achieved a 29% (95% CI 16–42) absolute risk reduction in antibiotic prescribing. This study was to assess the cost-effectiveness of our intervention at reducing antibiotic prescribing in rural primary care facilities as measured by the intervention's effect on the antibiotic prescription rates for childhood URTIs. Methods: We took a healthcare provider perspective, measuring costs of consultation (time cost of doctor), prescription monitoring process and peer-review meetings (time cost of participants) and medication costs. Costs on provider side were collected through a bespoke questionnaire from all 25 township hospitals in December 2016, while medication costs were collected prospectively in the trial. Incremental cost-effectiveness ratios were calculated by dividing the mean difference in cost of the two trial arms by the mean difference in antibiotic prescribing rate. Results: This showed an incremental cost of $0.03 per percentage point reduction in antibiotic prescribing. In addition to this incremental cost, the cost of implementing the intervention, including training and materials delivered by township hospitals, was $390.65 (SD $145.68) per healthcare facility. Conclusions: This study shows that a multifaceted intervention programme, when embedded into routine practice, is very cost-effective at reducing antibiotic prescribing in primary care facilities and has the potential of scale up in similar resource limited settings.

Background: Although supported self-management is a well-recognised part of chronic disease management, it has not been routinely used as part of healthcare for adults with a learning disability. We developed an intervention for adults with a mild or moderate learning disability and type 2 diabetes, building on the principles of supported self-management with reasonable adjustments made for the target population. Methods: in five steps, we:Clarified the principles of supported self-management as reported in the published literatureIdentified the barriers to effective self-management of type 2 diabetes in adults with a learning disabilityReviewed existing materials that aim to support self-management of diabetes for people with a learning disabilitySynthesised the outputs from the first three phases and identified elements of supported self-management that were (a) most relevant to the needs of our target population and (b) most likely to be acceptable and useful to themImplemented and field tested the intervention. Results: the final intervention had four standardised components: (1) establishing the participant's daily routines and lifestyle, (2) identifying supporters and their roles, (3) using this information to inform setting realistic goals and providing materials to the patient and supporter to help them be achieved and (4) monitoring progress against goals.Of 41 people randomised in a feasibility RCT, thirty five (85%) completed the intervention sessions, with over three quarters of all participants (78%) attending at least three sessions.Twenty-three out of 40 (58%) participants were deemed to be very engaged with the sessions and 12/40 (30%) with the materials; 30 (73%) participants had another person present with them during at least one of their sessions; 15/41 (37%) were reported to have a very engaged main supporter, and 18/41 (44%) had a different person who was not their main supporter but who was engaged in the intervention implementation. Conclusions: the intervention was feasible to deliver and, as judged by participation and engagement, acceptable to participants and those who supported them. Trial registration: Current Controlled Trials ISRCTN41897033 (registered 21/01/2013).

© 2018 Article author(s). Introduction for patients with advanced cancer, research shows that pain is frequent, burdensome and undertreated. Evidence-based approaches to support cancer pain management have been developed but have not been implemented within the context of the UK National Health Service. This protocol is for a pragmatic multicentre randomised controlled trial (RCT) to assess feasibility, acceptability, effectiveness and cost-effectiveness for a multicomponent intervention for pain management in patients with advanced cancer. Methods and analysis This trial will assess the feasibility of implementation and uptake of evidence-based interventions, developed and piloted as part of the Improving the Management of Pain from Advanced Cancer in the Community Programme grant, into routine clinical practice and determine whether there are potential differences with respect to patient-rated pain, patient pain knowledge and experience, healthcare use, quality of life and cost-effectiveness. 160 patients will receive either the intervention (usual care plus supported self-management) delivered within the oncology clinic and palliative care services by locally assigned community palliative care nurses, consisting of a self-management educational intervention and eHealth intervention for routine pain assessment and monitoring; or usual care. The primary outcomes are to assess implementation and uptake of the interventions, and differences in terms of pain severity. Secondary outcomes include pain interference, participant pain knowledge and experience, and cost-effectiveness. Outcome assessment will be blinded and patient-reported outcome measures collected via post at 6 and 12 weeks following randomisation. Ethics and dissemination This RCT has the potential to significantly influence National Health Service delivery to community-based patients with pain from advanced cancer. We aim to provide definitive evidence of whether two simple interventions delivered by community palliative care nurse in palliative care that support-self-management are clinically effective and cost-effective additions to standard community palliative care.

© 2018 the Author(s). Background: Residents of care homes have high levels of disability and poor mobility, but the promotion of health and wellbeing within care homes is poorly realised. Residents spend the majority of their time sedentary which leads to increased dependency and, coupled with poor postural management, can have many adverse outcomes including pressure sores, pain and reduced social interaction. The intervention being tested in this project (the Skilful Care Training Package) aims to increase the awareness and skills of care staff in relation to poor posture in the older, less mobile adult and highlight the benefits of activity, and how to skilfully assist activity, in this group to enable mobility and reduce falls risk. Feasibility work will be undertaken to inform the design of a definitive cluster randomised controlled trial. Methods: This is a cluster randomised controlled feasibility trial, aiming to recruit at least 12-15 residents at each of 10 care homes across Yorkshire. Care homes will be randomly allocated on a 1:1 basis to receive either the Skilful Care Training Package alongside usual care or to continue to provide usual care alone. Assessments will be undertaken by blinded researchers with participating residents at baseline (before care home randomisation) and at three and six months post randomisation. Data relating to changes in physical activity, mobility, posture, mood and quality of life will be collected. Data at the level of the home will also be collected and will include staff experience of care and changes in the numbers and types of adverse events residents experience (for example, hospital admissions, falls). Details of NHS service usage will be collected to inform the economic analysis. An embedded process evaluation will explore intervention delivery and its acceptability to staff and residents. Discussion: Participant uptake, engagement and retention are key feasibility outcomes. Exploration of barriers and facilitators to intervention delivery will inform intervention optimisation. Study results will inform progression to a definitive trial and add to the body of evidence for good practice in care home research. Trial registration: ISRCTN Registry, ISRCTN50080330. Registered on 27 March 2017.

© 2018 the Author(s). Background: There are more than a quarter of a million individuals aged ≥ 65 years who are resident in care homes in England and Wales. Care home residents have high levels of cognitive impairment, physical disability, multimorbidity and polypharmacy. Research is needed to ensure there are robust, evidence-based interventions to improve the quality of life of this frail group. However, there is a paucity of research studies in this area. Recruiting care homes and their residents to research is challenging. A feasibility, cluster randomised controlled trial was undertaken as part of a research programme to identify ways to develop and test methods to enhance the physical activity of care home residents. This paper describes two methods of recruiting care homes to the trial and draws out learning to inform future studies. Methods: Eligible care homes met the following criteria: they were within a defined geographical area in the north of England; provided residential care for adults ≥ 65 years of age; had not previously been involved in the research programme; were not taking part in a conflicting study; were not recorded on the Care Quality Commission website as 'inadequate' or 'requiring improvements' in any area; and had ≥ 10 beds. Care homes were identified by a 'systematic approach' using the Care Quality Commission website database of care homes or a 'targeted approach' via a network of research-ready care homes. A standardised method was used to recruit care homes including eligibility screening; invitation letters; telephone contact; visits; formal letter of agreement. Results: in the systematic approach, 377 care homes were screened, 230 (61%) were initially eligible and invited to participate, 11 were recruited (recruitment rate (RR) 4.8%). In the targeted approach, 15 care homes were invited to participate, two were recruited (RR 13.3%). Overall, 245 care homes were approached and 13 recruited (RR 5.3%). A variety of care homes were recruited to the trial in terms of size, location, ownership and care provision. Conclusions: Systematic recruitment of care homes to the study was time-consuming and resource-heavy but led to a variety of care homes being recruited. The targeted approach led to a higher recruitment rate. Trial registration: ISRCTN registry, ISRCTN16076575. Registered on 25 June 2015.

© 2018 the Author(s). Background: Interpreting evaluations of complex interventions can be difficult without sufficient description of key intervention content. We aimed to develop an implementation package for primary care which could be delivered using typically available resources and could be adapted to target determinants of behaviour for each of four quality indicators: diabetes control, blood pressure control, anticoagulation for atrial fibrillation and risky prescribing. We describe the development and prospective verification of behaviour change techniques (BCTs) embedded within the adaptable implementation packages. Methods: We used an over-lapping multi-staged process. We identified evidence-based, candidate delivery mechanisms-mainly audit and feedback, educational outreach and computerised prompts and reminders. We drew upon interviews with primary care professionals using the Theoretical Domains Framework to explore likely determinants of adherence to quality indicators. We linked determinants to candidate BCTs. With input from stakeholder panels, we prioritised likely determinants and intervention content prior to piloting the implementation packages. Our content analysis assessed the extent to which embedded BCTs could be identified within the packages and compared them across the delivery mechanisms and four quality indicators. Results: Each implementation package included at least 27 out of 30 potentially applicable BCTs representing 15 of 16 BCT categories. Whilst 23 BCTs were shared across all four implementation packages (e.g. BCTs relating to feedback and comparing behaviour), some BCTs were unique to certain delivery mechanisms (e.g. 'graded tasks' and 'problem solving' for educational outreach). BCTs addressing the determinants 'environmental context' and 'social and professional roles' (e.g. 'restructuring the social and 'physical environment' and 'adding objects to the environment') were indicator specific. We found it challenging to operationalise BCTs targeting 'environmental context', 'social influences' and 'social and professional roles' within our chosen delivery mechanisms. Conclusion: We have demonstrated a transparent process for selecting, operationalising and verifying the BCT content in implementation packages adapted to target four quality indicators in primary care. There was considerable overlap in BCTs identified across the four indicators suggesting core BCTs can be embedded and verified within delivery mechanisms commonly available to primary care. Whilst feedback reports can include a wide range of BCTs, computerised prompts can deliver BCTs at the time of decision making, and educational outreach can allow for flexibility and individual tailoring in delivery.

Background: an estimated 17,000 patients are treated annually in the UK with radical radiotherapy (RT) for pelvic cancer. New treatment approaches in RT have increased survivorship and changed the subjective toxicity profile for patients who experience acute and long-term pelvic-related adverse events (AE). Multi-disciplinary follow-up creates difficulty for monitoring and responding to these events during treatment and beyond. Originally developed for use in systemic oncology therapy eRAPID (electronic patient self-Reporting of Adverse-events: Patient Information and aDvice) is an online system for patients to report AEs from home. eRAPID enables patient data to be integrated into the electronic patient records for use in clinical practice, provides patient management advice for mild and moderate AE and advice to contact the hospital for severe AE. The system has now been developed for pelvic RT patients, and we aim to test the intervention in a pilot study with staff and patients to inform a future randomised controlled trial (RCT). Methods: Eligible patients are those attending St James's University hospital cancer centre and the Christie Hospital Manchester undergoing pelvic radiotherapy+/-chemotherapy/hormonotherapy for prostate, lower gastrointestinal and gynaecological cancers. A prospective 1:1 randomised (intervention or usual care) parallel group design with repeated measures and mixed methods will be employed. We aim to recruit 168 patients following recommendations for sample size estimates for pilot studies. Participants using eRAPID will report AE (at least weekly) from home weekly for 6 weeks and 6 weeks post-treatment (12-week total) then at 18 and 24 weeks. Hospital staff will review eRAPID reports and use information during consultations. Notifications will be sent to the relevant clinical team when severe symptoms are reported. We will measure patient-reported outcomes using validated questionnaires (Functional Assessment in Cancer Therapy Scale-General (FACT-G), European Organisation for Research and Treatment of Cancer Core Quality of Life questionnaire (EORTC-QLQ-C30), process of care impact (hospital records of patient contacts and admissions) and economic variables (EQ5D-5L, patient use of resources)). Staff and patient experiences will be explored via semi-structured interviews. Discussion: the objectives are to establish feasibility, recruitment, integrity of the system and attrition rates, determine effect sizes and aid selection of the primary outcome measure for a future RCT. We will also refine the intervention by exploring staff and patient views. The overall goal of this complex intervention is to improve the safe delivery of cancer treatments, enhance patient care and standardise documentation of AE within the clinical datasets. Trial registration: ClinicalTrials.gov NCT02747264.

© 2017 the Author(s). Background: Treatment of chronic lymphocytic leukaemia (CLL) has seen a substantial improvement over the last few years. Combination immunochemotherapy, such as fludarabine, cyclophosphamide and rituximab (FCR), is now standard first-line therapy. However, the majority of patients relapse and require further therapy, and so new, effective, targeted therapies that improve remission rates, reduce relapses, and have fewer side effects, are required. The FLAIR trial will assess whether ibrutinib plus rituximab (IR) is superior to FCR in terms of progression-free survival (PFS). Methods/design: FLAIR is a phase III, multicentre, randomised, controlled, open, parallel-group trial in patients with previously untreated CLL. A total of 754 participants will be randomised on a 1:1 basis to receive standard therapy with FCR or IR. Participants randomised to FCR will receive a maximum of six 28-day treatment cycles. Participants randomised to IR will receive six 28-day cycles of rituximab, and ibrutinib taken daily for 6 years until minimal residual disease (MRD) negativity has been recorded for the same amount of time as it took to become MRD negative, or until disease progression. The primary endpoint is PFS according to the International Workshop on CLL (IWCLL) criteria. Secondary endpoints include: overall survival; proportion of participants with undetectable MRD; response to therapy by IWCLL criteria; safety and toxicity; health-related quality of life (QoL); and cost-effectiveness. Discussion: the trial aims to provide evidence for the future first-line treatment of CLL patients by assessing whether IR is superior to FCR in terms of PFS, and whether toxicity rates are favourable. Trial registration:ISRCTN01844152. Registered on 8 August 2014, EudraCT number 2013-001944-76. Registered on 26 April 2013.

BACKGROUND: Family caregivers play an important role in the care of patients receiving palliative care, yet little is known about the financial impact of family caregiving in this context. A lack of existing validated tools for collecting data on the costs of family caregiving in palliative care has resulted in a weak and limited evidence base. The aim of the study was to describe the development and initial piloting of a new survey tool which captures data on the costs of family caregiving in palliative care: the Costs of Family Caregiving (COFAC) questionnaire. METHODS: Development and piloting of the COFAC questionnaire involved 2 phases: (1) questionnaire development based on published evidence and cognitive interviews with service users; and (2) validity testing involving expert review and piloting with bereaved caregivers. RESULTS: Questionnaire content was generated from previously published research and related to work-related costs, carer time costs and out-of-pocket expenses. 2 group cognitive interviews with 15 service users refined content of the draft questionnaire. Face validity was established through expert review with 9 academics and clinicians. Piloting with 8 bereaved caregivers established acceptability and feasibility of administration. CONCLUSIONS: the COFAC tool has been shown to be valid, acceptable to bereaved caregivers and feasible to administer. The COFAC questionnaire is recommended for economic research in palliative care which seeks to capture data from a broad societal perspective which includes family caregiver costs.

© 2017 the Author(s). Background: eRAPID (electronic patient self-Reporting of Adverse-events: Patient Information and aDvice) is an internet based system for patients to self-report symptoms and side effects (adverse events or AE) of cancer treatments. eRAPID allows AE reporting from home and patient reported data is accessible via Electronic Patient Records (EPR) for use in routine care. The system can generate alerts to clinical teams for severe AE and provides patient advice on managing mild AEs. The overall aims of eRAPID are to improve the safe delivery of cancer treatments, enhance patient care and standardise AE documentation. Methods: the trial is a prospective randomised two-arm parallel group design study with repeated measures and mixed methods. Participants (adult patients with breast cancer on neo-adjuvant or adjuvant chemotherapy, colorectal and gynaecological cancer receiving chemotherapy) are randomised to receive the eRAPID intervention or usual care over 18weeks of treatment. Participants in the intervention arm receive training in using the eRAPID system to provide routine weekly adverse event reports from home. Hospital staff can access eRAPID reports via the EPR and use the information during consultations or phone calls with patients. Prior to commencing the full trial an internal pilot phase was conducted (N=87 participants) to assess recruitment procedures, consent and attrition rates, the integrity of the intervention information technology and establish procedures for collecting outcome data. The overall target sample for the trial is N=504. The primary outcome of the trial is quality of life (FACT-G) with secondary outcomes including health economics (costs to patients and the NHS), process of care (e.g. contacts with the hospital, number of admissions, clinic appointments and changes to treatment/medications) and patient self-efficacy. Outcome data is collected at baseline, 6, 12, 18weeks and 12months. The intervention is also being evaluated via end of study interviews with patient participants and clinical staff. Discussion: the pilot phase was completed in February 2016 and recruitment and attrition rates met criteria for continuing to the full trial. Recruitment recommenced in May 2016 and is planned to continue until December 2017. Overall findings will determine the value of the eRAPID intervention for supporting the care of patients receiving systemic cancer treatment. Trial registration: Current Controlled Trials ISRCTN88520246. Registered 11 September 2014.

© Queen’s Printer and Controller of HMSO 2017. Background: Planned neck dissection (ND) after radical chemoradiotherapy (CRT) for locally advanced nodal metastases in patients with head and neck squamous cell carcinoma (HNSCC) remains controversial. Thirty per cent of ND specimens show histological evidence of tumour. Consequently, a significant proportion of clinicians still practise planned ND. Fludeoxyglucose positron emission tomography (PET)-computerised tomography (CT) scanning demonstrated high negative predictive values for persistent nodal disease, providing a possible alternative paradigm to ND. Evidence is sparse and drawn mainly from retrospective single-institution studies, illustrating the need for a prospective randomised controlled trial. Objectives: to determine the efficacy and cost-effectiveness of PET-CT-guided surveillance, compared with planned ND, in a multicentre, prospective, randomised setting. Design: a pragmatic randomised non-inferiority trial comparing PET-CT-guided watch-and-wait policy with the current planned ND policy in HNSCC patients with locally advanced nodal metastases and treated with radical CRT. Patients were randomised in a 1: 1 ratio. Primary outcomes were overall survival (OS) and cost-effectiveness [incremental cost per incremental quality-adjusted life-year (QALY)]. Cost-effectiveness was assessed over the trial period using individual patient data, and over a lifetime horizon using a decision-analytic model. Secondary outcomes were recurrence in the neck, complication rates and quality of life. The recruitment of 560 patients was planned to detect non-inferior OS in the intervention arm with a 90% power and a type I error of 5%, with non-inferiority defined as having a hazard ratio (HR) of no higher than 1.50. An intention-to-treat analysis was performed by Cox’s proportional hazards model. Settings: Thirty-seven head and neck cancer-treating centres (43 NHS hospitals) throughout the UK. Participants: Patients with locally advanced nodal metastases of oropharynx, hypopharynx, larynx, oral or occult HNSCC receiving CRT and fit for ND were recruited. Intervention: Patients randomised to planned ND before or after CRT (control), or CRT followed by fludeoxyglucose PET-CT 10-12 weeks post CRT with ND only if PET-CT showed incomplete or equivocal response of nodal disease (intervention). Balanced by centre, planned ND timing, CRT schedule, disease site and the tumour, node, metastasis stage. Results: in total, 564 patients were recruited (ND arm, n = 282; and surveillance arm, n = 282; 17% N2a, 61% N2b, 18% N2c and 3% N3). Eighty-four per cent had oropharyngeal cancer. Seventy-five per cent of tested cases were p16 positive. The median time to follow-up was 36 months. The HR for OS was 0.92 [95% confidence interval (CI) 0.65 to 1.32], indicating non-inferiority. The upper limit of the non-inferiority HR margin of 1.50, which was informed by patient advisors to the project, lies at the 99.6 percentile of this estimate (p = 0.004). There were no differences in this result by p16 status. There were 54 NDs performed in the surveillance arm, with 22 surgical complications, and 221 NDs in the ND arm, with 85 complications. Quality-of-life scores were slightly better in the surveillance arm. Compared with planned ND, PET-CT surveillance produced an incremental net health benefit of 0.16 QALYs (95% CI 0.03 to 0.28 QALYs) over the trial period and 0.21 QALYs (95% CI-0.41 to 0.85 QALYs) over the modelled lifetime horizon. Limitations: Pragmatic randomised controlled trial with a 36-month median follow-up. Conclusions: PET-CT-guided active surveillance showed similar survival outcomes to ND but resulted in considerably fewer NDs, fewer complications and lower costs, supporting its use in routine practice. Future work: PET-CT surveillance is cost-effective in the short term, and long-term cost-effectiveness could be addressed in future work.

© 2017, Springer International Publishing Switzerland. Background: Pain from advanced cancer remains prevalent, severe and often under-treated. Aim: the aim of this study was to conduct a discrete choice experiment with patients to understand their preferences for pain management services and inform service development. Methods: Focus groups were used to develop the attributes and levels of the discrete choice experiment. The attributes were: waiting time, type of healthcare professional, out-of-pocket costs, side-effect control, quality of communication, quality of information and pain control. Patients completed the discrete choice experiment along with clinical and health-related quality of life questions. Conditional and mixed logit models were used to analyse the data. Results: Patients with cancer pain (n = 221) and within palliative care services completed the survey (45% were female, mean age 64.6 years; age range 21–92 years). The most important aspects of pain management were: good pain control, zero out-of-pocket costs and good side-effect control. Poor or moderate pain control and £30 costs drew the highest negative preferences. Respondents preferred control of side effects and provision of better information and communication, over access to certain healthcare professionals. Those with lower health-related quality of life were less willing to wait for treatment and willing to incur higher costs. The presence of a carer influenced preferences. Conclusions: Outcome attributes were more important than process attributes but the latter were still valued. Thus, supporting self-management, for example by providing better information on pain may be a worthwhile endeavour. However, service provision may need to account for individual characteristics given the heterogeneity in preferences.

© Queen’s Printer and Controller of HMSO 2017. Background: Mechanical chest compression devices may help to maintain high-quality cardiopulmonary resuscitation (CPR), but little evidence exists for their effectiveness. We evaluated whether or not the introduction of Lund University Cardiopulmonary Assistance System-2 (LUCAS-2; Jolife AB, Lund, Sweden) mechanical CPR into front-line emergency response vehicles would improve survival from out-of-hospital cardiac arrest (OHCA). Objective: Evaluation of the LUCAS-2 device as a routine ambulance service treatment for OHCA. Design: Pragmatic, cluster randomised trial including adults with non-traumatic OHCA. Ambulance dispatch staff and those collecting the primary outcome were blind to treatment allocation. Blinding of the ambulance staff who delivered the interventions and reported initial response to treatment was not possible. We also conducted a health economic evaluation and a systematic review of all trials of out-of-hospital mechanical chest compression. Setting: Four UK ambulance services (West Midlands, North East England, Wales and South Central), comprising 91 urban and semiurban ambulance stations. Clusters were ambulance service vehicles, which were randomly assigned (approximately 1: 2) to the LUCAS-2 device or manual CPR. Participants: Patients were included if they were in cardiac arrest in the out-of-hospital environment. Exclusions were patients with cardiac arrest as a result of trauma, with known or clinically apparent pregnancy, or aged < 18 years. Interventions: Patients received LUCAS-2 mechanical chest compression or manual chest compressions according to the first trial vehicle to arrive on scene. Main outcome measures: Survival at 30 days following cardiac arrest; survival without significant neurological impairment [Cerebral Performance Category (CPC) score of 1 or 2]. Results: We enrolled 4471 eligible patients (1652 assigned to the LUCAS-2 device and 2819 assigned to control) between 15 April 2010 and 10 June 2013. A total of 985 (60%) patients in the LUCAS-2 group received mechanical chest compression and 11 (< 1%) patients in the control group received LUCAS-2. In the intention-to-treat analysis, 30-day survival was similar in the LUCAS-2 (104/1652, 6.3%) and manual CPR groups [193/2819, 6.8%; adjusted odds ratio (OR) 0.86, 95% confidence interval (CI) 0.64 to 1.15]. Survival with a CPC score of 1 or 2 may have been worse in the LUCAS-2 group (adjusted OR 0.72, 95% CI 0.52 to 0.99). No serious adverse events were noted. The systematic review found no evidence of a survival advantage if mechanical chest compression was used. The health economic analysis showed that LUCAS-2 was dominated by manual chest compression. Limitations: There was substantial non-compliance in the LUCAS-2 arm. For 272 out of 1652 patients (16.5%), mechanical chest compression was not used for reasons that would not occur in clinical practice. We addressed this issue by using complier average causal effect analyses. We attempted to measure CPR quality during the resuscitation attempts of trial participants, but were unable to do so. Conclusions: There was no evidence of improvement in 30-day survival with LUCAS-2 compared with manual compressions. Our systematic review of recent randomised trials did not suggest that survival or survival without significant disability may be improved by the use of mechanical chest compression. Limitations: There was substantial non-compliance in the LUCAS-2 arm. For 272 out of 1652 patients (16.5%), mechanical chest compression was not used for reasons that would not occur in clinical practice. We addressed this issue by using complier average causal effect analyses. We attempted to measure CPR quality during the resuscitation attempts of trial participants, but were unable to do so. Conclusions: There was no evidence of improvement in 30-day survival with LUCAS-2 compared with manual compressions. Our systematic review of recent randomised trials did not suggest that survival or survival without significant disability may be improved by the use of mechanical chest compression. Future work: the use of mechanical chest compression for in-hospital cardiac arrest, and in specific circumstances (e.g. transport), has not yet been evaluated.

© 2017, American College of Rheumatology Objective: to investigate whether rituximab, an anti–B cell therapy, improves symptoms of fatigue and oral dryness in patients with primary Sjögren's syndrome (SS). Methods: We conducted a multicenter, randomized, double-blind, placebo-controlled, parallel-group trial that included health economic analysis. Anti-Ro–positive patients with primary SS, symptomatic fatigue, and oral dryness were recruited from 25 UK rheumatology clinics from August 2011 to January 2014. Patients were centrally randomized to receive either intravenous (IV) placebo (250 ml saline) or IV rituximab (1,000 mg in 250 ml saline) in 2 courses at weeks 0, 2, 24, and 26, with pre- and postinfusion medication including corticosteroids. The primary end point was the proportion of patients achieving a 30% reduction in either fatigue or oral dryness at 48 weeks, as measured by visual analog scale. Other outcome measures included salivary and lacrimal flow rates, quality of life, scores on the European League Against Rheumatism (EULAR) Sjögren's Syndrome Patient Reported Index and EULAR Sjögren's Syndrome Disease Activity Index, symptoms of ocular and overall dryness, pain, globally assessed disease activity, and cost-effectiveness. Results: all 133 patients who were randomized to receive placebo (n = 66) or rituximab (n = 67) were included in the primary analysis. Among patients with complete data, 21 of 56 placebo-treated patients and 24 of 61 rituximab-treated patients achieved the primary end point. After multiple imputation of missing outcomes, response rates in the placebo and rituximab groups were 36.8% and 39.8%, respectively (adjusted odds ratio 1.13 [95% confidence interval 0.50, 2.55]). There were no significant improvements in any outcome measure except for unstimulated salivary flow. The mean ± SD costs per patient for rituximab and placebo were £10,752 ± 264.75 and £2,672 ± 241.71, respectively. There were slightly more adverse events (AEs) reported in total for rituximab, but there was no difference in serious AEs (10 in each group). Conclusion: the results of this study indicate that rituximab is neither clinically effective nor cost-effective in this patient population.

© 2017 the Author(s). Background: As life expectancy increases and the number of older people, particularly those aged 85years and over, expands there is an increase in demand for long-term care. A large proportion of people in a care home setting spend most of their time sedentary, and this is one of the leading preventable causes of death. Encouraging residents to engage in more physical activity could deliver benefits in terms of physical and psychological health, and quality of life. This study is the final stage of a programme of research to develop and preliminarily test an evidence-based intervention designed to enhance opportunities for movement amongst care home residents, thereby increasing levels of physical activity. Methods/design: This is a cluster randomised feasibility trial, aiming to recruit at least 8-12 residents at each of 12 residential care homes across Yorkshire, UK. Care homes will be randomly allocated on a 1:1 basis to receive either the intervention alongside usual care, or to continue to provide usual care alone. Assessment will be undertaken with participating residents at baseline (prior to care home randomisation) and at 3, 6, and 9months post-randomisation. Data relating to changes in physical activity, physical function, level of cognitive impairment, mood, perceived health and wellbeing, and quality of life will be collected. Data at the level of the home will also be collected and will include staff experience of care, and changes in the numbers and types of adverse events residents experience (for example, hospital admissions, falls). Details of National Health Service (NHS) usage will be collected to inform the economic analysis. An embedded process evaluation will obtain information to test out the theory of change underpinning the intervention and its acceptability to staff and residents. Discussion: This feasibility trial with embedded process evaluation and collection of health economic data will allow us to undertake detailed feasibility work to inform a future large-scale trial. It will provide valuable information to inform research procedures in this important but challenging area. Trial registration: ISRCTN registry, ISRCTN16076575. Registered on 25 June 2015.

© 2017 the Author(s). Background: Simvastatin therapy for patients with acute respiratory distress syndrome (ARDS) has been shown to be safe and associated with minimal adverse effects, but it does not improve clinical outcomes. The aim of this research was to report on mortality and cost-effectiveness of simvastatin in patients with ARDS at 12 months. Methods: This was a cost-utility analysis alongside a multicentre, double-blind, randomised controlled trial carried out in the UK and Ireland. Five hundred and forty intubated and mechanically ventilated patients with ARDS were randomly assigned (1:1) to receive once-daily simvastatin (at a dose of 80 mg) or identical placebo tablets enterally for up to 28 days. Results: Mortality was lower in the simvastatin group (31.8%, 95% confidence interval (CI) 26.1-37.5) compared to the placebo group (37.3%, 95% CI 31.6-43.0) at 12 months, although this was not significant. Simvastatin was associated with statistically significant quality-adjusted life year (QALY) gain (incremental QALYs 0.064, 95% CI 0.002-0.127) compared to placebo. Simvastatin was also less costly (incremental total costs -£3601, 95% CI -8061 to 859). At a willingness-to-pay threshold of £20,000 per QALY, the probability of simvastatin being cost-effective was 99%. Sensitivity analyses indicated that the results were robust to changes in methodological assumptions with the probability of cost-effectiveness never dropping below 90%. Conclusion: Simvastatin was found to be cost-effective for the treatment of ARDS, being associated with both a significant QALY gain and a cost saving. There was no significant reduction in mortality at 12 months, Trial registration: ISRCTN, 88244364. Registered 26 November 2010.

© 2017 the Author(s). Background: This paper describes the design and development of a complex multifactorial falls prevention (MFFP) intervention for implementation and testing within the framework of a large UK-based falls prevention randomised controlled trial (RCT). Methods: a complex intervention was developed for inclusion within the Prevention of Falls Injury Trial (PreFIT), a multicentre pragmatic RCT. PreFIT aims to compare the clinical and cost-effectiveness of three alternative primary care falls prevention interventions (advice, exercise and MFFP), on outcomes of fractures and falls. Community-dwelling adults, aged 70 years and older, were recruited from primary care in the National Health Service (NHS), England. Results: Development of the PreFIT MFFP intervention was informed by the existing evidence base and clinical guidelines for the assessment and management of falls in older adults. After piloting and modification, the final MFFP intervention includes seven falls risk factors: a detailed falls history interview with consideration of ‘red flags’; assessment of balance and gait; vision; medication screen; cardiac screen; feet and footwear screen and home environment assessment. This complex intervention has been fully manualised with clear, documented assessment and treatment pathways for each risk factor. Each risk factor is assessed in every trial participant referred for MFFP. Referral for assessment is based upon a screening survey to identify those with a history of falling or balance problems. Intervention delivery can be adapted to the local setting. Conclusion: This complex falls prevention intervention is currently being tested within the framework of a large clinical trial. This paper adheres to TIDieR and CONSORT recommendations for the comprehensive and explicit reporting of trial interventions. Results from the PreFIT study will be published in due course. The effectiveness and cost-effectiveness of the PreFIT MFFP intervention, compared to advice and exercise, on the prevention of falls and fractures, will be reported at the conclusion of the trial.

© 2017, BMJ Publishing Group. All rights reserved. Introduction: to understand the variation in performance between community hospitals, our objectives are: to measure the relative performance (cost efficiency) of rehabilitation services in community hospitals; to identify the characteristics of community hospital rehabilitation that optimise performance; to investigate the current impact of community hospital inpatient rehabilitation for older people on secondary care and the potential impact if community hospital rehabilitation was optimised to best practice nationally; to examine the relationship between the configuration of intermediate care and secondary care bed use; and to develop toolkits for commissioners and community hospital providers to optimise performance. Methods and analysis: 4 linked studies will be performed. Study 1: cost efficiency modelling will apply econometric techniques to data sets from the National Health Service (NHS) Benchmarking Network surveys of community hospital and intermediate care. This will identify community hospitals' performance and estimate the gap between high and low performers. Analyses will determine the potential impact if the performance of all community hospitals nationally was optimised to best performance, and examine the association between community hospital configuration and secondary care bed use. Study 2: a national community hospital survey gathering detailed cost data and efficiency variables will be performed. Study 3: in-depth case studies of 3 community hospitals, 2 high and 1 low performing, will be undertaken. Case studies will gather routine hospital and local health economy data. Ward culture will be surveyed. Content and delivery of treatment will be observed. Patients and staff will be interviewed. Study 4: co-designed web-based quality improvement toolkits for commissioners and providers will be developed, including indicators of performance and the gap between local and best community hospitals performance. Ethics and dissemination: Publications will be in peer-reviewed journals, reports will be distributed through stakeholder organisations. Ethical approval was obtained from the Bradford Research Ethics Committee (reference: 15/YH/0062).

© 2017 International Society for Pharmacoeconomics and Outcomes Research (ISPOR) Background Precision medicine is heralded as offering more effective treatments to smaller targeted patient populations. In breast cancer, adjuvant chemotherapy is standard for patients considered as high-risk after surgery. Molecular tests may identify patients who can safely avoid chemotherapy. Objectives to use economic analysis before a large-scale clinical trial of molecular testing to confirm the value of the trial and help prioritize between candidate tests as randomized comparators. Methods Women with surgically treated breast cancer (estrogen receptor–positive and lymph node–positive or tumor size ≥30 mm) were randomized to standard care (chemotherapy for all) or test-directed care using Oncotype DX™. Additional testing was undertaken using alternative tests: MammaPrintTM, PAM-50 (ProsignaTM), MammaTyperTM, IHC4, and IHC4-AQUA™ (NexCourse Breast™). A probabilistic decision model assessed the cost-effectiveness of all tests from a UK perspective. Value of information analysis determined the most efficient publicly funded ongoing trial design in the United Kingdom. Results There was an 86% probability of molecular testing being cost-effective, with most tests producing cost savings (range −£1892 to £195) and quality-adjusted life-year gains (range 0.17–0.20). There were only small differences in costs and quality-adjusted life-years between tests. Uncertainty was driven by long-term outcomes. Value of information demonstrated value of further research into all tests, with Prosigna currently being the highest priority for further research. Conclusions Molecular tests are likely to be cost-effective, but an optimal test is yet to be identified. Health economics modeling to inform the design of a randomized controlled trial looking at diagnostic technology has been demonstrated to be feasible as a method for improving research efficiency.

Copyright © 2017 Willis et al.This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Background: There are widely recognised variations in the delivery and outcomes of healthcare but an incomplete understanding of their causes. There is a growing interest in using routinely collected 'big data' in the evaluation of healthcare. We developed a set of evidence-based 'high impact' quality indicators (QIs) for primary care and examined variations in achievement of these indicators using routinely collected data in the United Kingdom (UK). Methods: Cross-sectional analysis of routinely collected, electronic primary care data from a sample of general practices in West Yorkshire, UK (n = 89). The QIs covered aspects of care (including processes and intermediate clinical outcomes) in relation to diabetes, hypertension, atrial fibrillation, myocardial infarction, chronic kidney disease (CKD) and 'risky' prescribing combinations. Regression models explored the impact of practice and patient characteristics. Clustering within practice was accounted for by including a random intercept for practice. Results: Median practice achievement of the QIs ranged from 43.2% (diabetes control) to 72.2% (blood pressure control in CKD). Considerable between-practice variation existed for all indicators: the difference between the highest and lowest performing practices was 26.3 percentage points for risky prescribing and 100 percentage points for anticoagulation in atrial fibrillation. Odds ratios associated with the random effects for practices emphasised this; there was a greater than ten-fold difference in the likelihood of achieving the hypertension indicator between the lowest and highest performing practices. Patient characteristics, in particular age, gender and comorbidity, were consistently but modestly associated with indicator achievement. Statistically significant practice characteristics were identified less frequently in adjusted models. Conclusions: Despite various policy and improvement initiatives, there are enduring inappropriate variations in the delivery of evidence-based care. Much of this variation is not explained by routinely collected patient or practice variables, and is likely to be attributable to differences in clinical and organisational behaviour.

Introduction: Falls are the leading cause of accident-related mortality in older adults. Injurious falls are associated with functional decline, disability, healthcare utilisation and significant National Health Service (NHS)-related costs. The evidence base for multifactorial or exercise interventions reducing fractures in the general population is weak. This protocol describes a large-scale UK trial investigating the clinical and cost-effectiveness of alternative falls prevention interventions targeted at community dwelling older adults. Methods and analysis: a three-arm, pragmatic, cluster randomised controlled trial, conducted within primary care in England, UK. Sixty-three general practices will be randomised to deliver one of three falls prevention interventions: (1) advice only; (2) advice with exercise; or (3) advice with multifactorial falls prevention (MFFP). We aim to recruit over 9000 community-dwelling adults aged 70 and above. Practices randomised to deliver advice will mail out advice booklets. Practices randomised to deliver 'active' interventions, either exercise or MFFP, send all trial participants the advice booklet and a screening survey to identify participants with a history of falling or balance problems. Onward referral to 'active' intervention will be based on falls risk determined from balance screen. The primary outcome is peripheral fracture; secondary outcomes include number with at least one fracture, falls, mortality, quality of life and health service resource use at 18 months, captured using self-report and routine healthcare activity data. Ethics and dissemination: the study protocol has approval from the National Research Ethics Service (REC reference 10/H0401/36; Protocol V.3.1, 21/May/ 2013). User groups and patient representatives were consulted to inform trial design. Results will be reported at conferences and in peer-reviewed publications. A patient-friendly summary of trial findings will be published on the prevention of falls injury trial (PreFIT) website. This protocol adheres to the recommended SPIRIT Checklist. Amendments will be reported to relevant regulatory parties.

© 2015, the Author(s). Purpose: Cancer-related fatigue (CRF) is a frequent and distressing symptom experienced after cancer treatment. RESTORE is the first web-based resource designed to enhance self-efficacy to manage CRF following curative-intent treatment. The aim of this study is to test the proof of concept and inform the design of an effectiveness trial. Methods: a multi-centre parallel-group two-armed (1:1) exploratory randomised controlled trial (RCT) with qualitative process evaluation was employed in the study. Participants (≥18 years; ≤5 years post treatment with moderate to severe fatigue) were recruited and randomly assigned to RESTORE or a leaflet. Feasibility and acceptability were measured by recruitment, attrition, intervention adherence, completion of outcome measures and process evaluation. Change in self-efficacy to manage CRF was also explored. Outcome measures were completed at baseline (T0), 6 weeks (T1) and 12 weeks (T2). Data were analysed using mixed-effects linear regression and directed content analysis. Results: One hundred and sixty-three people participated in the trial and 19 in the process evaluation. The intervention was feasible (39 % of eligible patients consented) and acceptable (attrition rate 36 %). There was evidence of higher fatigue self-efficacy at T1 in the intervention group vs comparator (mean difference 0.51 [−0.08 to 1.11]), though the difference in groups decreased by 12 weeks. Time since diagnosis influenced perceived usefulness of the intervention. Modifications were suggested. Conclusion: Proof of concept was achieved. The RESTORE intervention should be subject to a definitive trial with some adjustments. Provision of an effective supportive resource would empower cancer survivors to manage CRF after treatment completion. Trial registration: ISRCTN67521059

© 2016 Willis et al. Background: There are recognised gaps between evidence and practice in general practice, a setting which provides particular challenges for implementation. We earlier screened clinical guideline recommendations to derive a set of 'high impact' indicators based upon criteria including potential for significant patient benefit, scope for improved practice and amenability to measurement using routinely collected data. We aim to evaluate the effectiveness and cost-effectiveness of a multifaceted, adaptable intervention package to implement four targeted, high impact recommendations in general practice. Methods/design: the research programme Action to Support Practice Implement Research Evidence (ASPIRE) includes a pair of pragmatic cluster-randomised trials which use a balanced incomplete block design. Clusters are general practices in West Yorkshire, United Kingdom (UK), recruited using an 'opt-out' recruitment process. The intervention package adapted to each recommendation includes combinations of audit and feedback, educational outreach visits and computerised prompts with embedded behaviour change techniques selected on the basis of identified needs and barriers to change. In trial 1, practices are randomised to adapted interventions targeting either diabetes control or risky prescribing and those in trial 2 to adapted interventions targeting either blood pressure control in patients at risk of cardiovascular events or anticoagulation in atrial fibrillation. The respective primary endpoints comprise achievement of all recommended target levels of haemoglobin A1c (HbA1c), blood pressure and cholesterol in patients with type 2 diabetes, a composite indicator of risky prescribing, achievement of recommended blood pressure targets for specific patient groups and anticoagulation prescribing in patients with atrial fibrillation. We are also randomising practices to a fifth, non-intervention control group to further assess Hawthorne effects. Outcomes will be assessed using routinely collected data extracted 1 year after randomisation. Economic modelling will estimate intervention cost-effectiveness. A process evaluation involving eight non-trial practices will examine intervention delivery, mechanisms of action and unintended consequences. Discussion: ASPIRE will provide 'real-world' evidence about the effects, cost-effectiveness and delivery of adapted intervention packages targeting high impact recommendations. By implementing our adaptable intervention package across four distinct clinical topics, and using 'opt-out' recruitment, our findings will provide evidence of wider generalisability. Trial registration:ISRCTN91989345

© Published by the BMJ Publishing Group Limited. Objectives to investigate whether there is an association between differences in travel time/travel distance to healthcare services and patients' health outcomes and assimilate the methodologies used to measure this. Design Systematic Review. We searched MEDLINE, Embase, Web of Science, Transport database, HMIC and EBM Reviews for studies up to 7 September 2016. Studies were excluded that included children (including maternity), emergency medical travel or countries classed as being in the global south. Settings a wide range of settings within primary and secondary care (these were not restricted in the search). Results 108 studies met the inclusion criteria. The results were mixed. 77% of the included studies identified evidence of a distance decay association, whereby patients living further away from healthcare facilities they needed to attend had worse health outcomes (eg, survival rates, length of stay in hospital and non-attendance at follow-up) than those who lived closer. 6 of the studies identified the reverse (a distance bias effect) whereby patients living at a greater distance had better health outcomes. The remaining 19 studies found no relationship. There was a large variation in the data available to the studies on the patients' geographical locations and the healthcare facilities attended, and the methods used to calculate travel times and distances were not consistent across studies. Conclusions the review observed that a relationship between travelling further and having worse health outcomes cannot be ruled out and should be considered within the healthcare services location debate.

© 2016 Rautenberg et al. Background: Although guidance on good research practice in health economic modeling is widely available, there is still a need for a simpler instructive resource which could guide a beginner modeler alongside modeling for the first time. Aim: to develop a beginner’s guide to be used as a handheld guide contemporaneous to the model development process. Methods: a systematic review of best practice guidelines was used to construct a framework of steps undertaken during the model development process. Focused methods review supplemented this framework. Consensus was obtained among a group of model developers to review and finalize the content of the preliminary beginner’s guide. The final beginner’s guide was used to develop cost-effectiveness models. Results: Thirty-two best practice guidelines were data extracted, synthesized, and critically evaluated to identify steps for model development, which formed a framework for the beginner’s guide. Within five phases of model development, eight broad submethods were identified and 19 methodological reviews were conducted to develop the content of the draft beginner’s guide. Two rounds of consensus agreement were undertaken to reach agreement on the final beginner’s guide. To assess fitness for purpose (ease of use and completeness), models were developed independently and by the researcher using the beginner’s guide. Conclusion: a combination of systematic review, methods reviews, consensus agreement, and validation was used to construct a step-by-step beginner’s guide for developing decision analytical cost-effectiveness models. The final beginner’s guide is a step-by-step resource to accompany the model development process from understanding the problem to be modeled, model conceptualization, model implementation, and model checking through to reporting of the model results.

© 2016, Springer International Publishing Switzerland. Many healthcare organizations are now making good use of electronic health record (EHR) systems to record clinical information about their patients and the details of their healthcare. Electronic data in EHRs is generated by people engaged in complex processes within complex environments, and their human input, albeit shaped by computer systems, is compromised by many human factors. These data are potentially valuable to health economists and outcomes researchers but are sufficiently large and complex enough to be considered part of the new frontier of ‘big data’. This paper describes emerging methods that draw together data mining, process modelling, activity-based costing and dynamic simulation models. Our research infrastructure includes safe links to Leeds hospital’s EHRs with 3 million secondary and tertiary care patients. We created a multidisciplinary team of health economists, clinical specialists, and data and computer scientists, and developed a dynamic simulation tool called NETIMIS (Network Tools for Intervention Modelling with Intelligent Simulation; http://www.netimis.com) suitable for visualization of both human-designed and data-mined processes which can then be used for ‘what-if’ analysis by stakeholders interested in costing, designing and evaluating healthcare interventions. We present two examples of model development to illustrate how dynamic simulation can be informed by big data from an EHR. We found the tool provided a focal point for multidisciplinary team work to help them iteratively and collaboratively ‘deep dive’ into big data.

BACKGROUND: the long-term economic and quality-of-life outcomes of patients admitted to intensive care unit (ICU) with acute respiratory distress syndrome are not well understood. In this study, we investigate 1-year costs, survival and quality of life following ICU admission in patients who required mechanical ventilation for acute respiratory distress syndrome. METHODS: Economic analysis of data collected alongside a UK-based multi-centre randomised, controlled trial, aimed at comparing high-frequency oscillatory ventilation with conventional mechanical ventilation. The study included 795 critically ill patients admitted to ICU. Hospital costs were assessed using daily data. Post-hospital healthcare costs, patient out-of-pocket expenses, lost earnings of survivors and their carers and health-related quality of life were assessed using follow-up surveys. RESULTS: the mean cost of initial ICU stay was £26,857 (95 % CI £25,222-£28,491), and the average daily cost in ICU was £1738 (CI £1667-£1810). Following hospital discharge, the average 1-year cost among survivors was £7523 (CI £5692-£9354). The mean societal cost at 1 year was £44,077 (£41,168-£46,985), and the total societal cost divided by the number of 1-year survivors was £90,206. Survivors reported significantly lower health-related quality of life than the age- and sex-matched reference population, and this difference was more marked in younger patients. CONCLUSIONS: Given the high costs and low health-related quality of life identified, there is significant scope for further research aimed at improving care in this in-need patient group. TRIAL REGISTRATION: ISRCTN10416500.

© 2016 Foster et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Purpose: This paper identifies predictors of recovery trajectories of quality of life (QoL), health status and personal wellbeing in the two years following colorectal cancer surgery. Methods: 872 adults receiving curative intent surgery during November 2010 to March 2012. Questionnaires at baseline, 3, 9, 15, 24 months post-surgery assessed QoL, health status, wellbeing, confidence to manage illness-related problems (self-efficacy), social support, comorbidities, socio-demographic, clinical and treatment characteristics. Group-based trajectory analyses identified distinct trajectories and predictors for QoL, health status and wellbeing. Results: Four recovery trajectories were identified for each outcome. Groups 1 and 2 fared consistently well (scores above/within normal range); 70.5% of participants for QoL, 33.3% health status, 77.6% wellbeing. Group 3 had some problems (24.2% QoL, 59.3% health, 18.2% wellbeing); Group 4 fared consistently poorly (5.3% QoL, 7.4% health, 4.2% wellbeing). Higher pre-surgery depression and lower self-efficacy were significantly associated with poorer trajectories for all three outcomes after adjusting for other important predictors including disease characteristics, stoma, anxiety and social support. Conclusions: Psychosocial factors including self-efficacy and depression before surgery predict recovery trajectories in QoL, health status and wellbeing following colorectal cancer treatment independent of treatment or disease characteristics. This has significant implications for colorectal cancer management as appropriate support may be improved by early intervention resulting in more positive recovery experiences.

© 2016 the Author(s). Background: Pressure ulcers represent a major burden to patients, carers and the healthcare system, affecting approximately 1 in 17 hospital and 1 in 20 community patients. They impact greatly on an individual's functional status and health-related quality of life. The mainstay of pressure ulcer prevention practice is the provision of pressure redistribution support surfaces and patient repositioning. The aim of the PRESSURE 2 study is to compare the two main mattress types utilised within the NHS: high-specification foam and alternating pressure mattresses, in the prevention of pressure ulcers. Methods/Design: PRESSURE 2 is a multicentre, open-label, randomised, double triangular, group sequential, parallel group trial. A maximum of 2954 'high-risk' patients with evidence of acute illness will be randomised on a 1:1 basis to receive either a high-specification foam mattress or alternating-pressure mattress in conjunction with an electric profiling bed frame. The primary objective of the trial is to compare mattresses in terms of the time to developing a new Category 2 or above pressure ulcer by 30 days post end of treatment phase. Secondary endpoints include time to developing new Category 1 and 3 or above pressure ulcers, time to healing of pre-existing Category 2 pressure ulcers, health-related quality of life, cost-effectiveness, incidence of mattress change and safety. Validation objectives are to determine the responsiveness of the Pressure Ulcer Quality of Life-Prevention instrument and the feasibility of having a blinded endpoint assessment using photography. The trial will have a maximum of three planned analyses with unequally spaced reviews at event-driven coherent cut-points. The futility boundaries are constructed as non-binding to allow a decision for stopping early to be overruled by the Data Monitoring and Ethics Committee. Discussion: the double triangular, group sequential design of the PRESSURE 2 trial will provide an efficient design through the possibility of early stopping for demonstrating either superiority, inferiority of mattresses or futility of the trial. The trial optimises the potential for producing robust clinical evidence on the effectiveness of two commonly used mattresses in clinical practice earlier than in a conventional design. Trial registration:ISRCTN01151335. Registered on 14 May 2013. Protocol version: 5.0, dated 25 September 2015 Trial sponsor: Clare Skinner, Faculty Head of Research Support, University of Leeds, Leeds, LS2 9JT; 0113 343 4897; C.E.Skinner@leeds.ac.uk.

© 2016, the Author(s). Purpose: Faecal incontinence is a physically, psychologically and socially disabling condition. NICE guidance (2007) recommends surgical intervention, including sacral nerve stimulation (SNS), after failed conservative therapies. The FENIX™ magnetic sphincter augmentation (MSA) device is a novel continence device consisting of a flexible band of interlinked titanium beads with magnetic cores that is placed around the anal canal to augment anal sphincter tone through passive attraction of the beads. Preliminary studies suggest the FENIX™ MSA is safe, but efficacy data is limited. Rigorous evaluation is required prior to widespread adoption. Method and design: the SaFaRI trial is a National Institute of Health Research (NIHR) Health Technology Assessment (HTA)-funded UK multi-site, parallel group, randomised controlled, unblinded trial that will investigate the use of the FENIX™ MSA, as compared to SNS, for adult faecal incontinence resistant to conservative management. Twenty sites across the UK, experienced in the treatment of faecal incontinence, will recruit 350 patients randomised equally to receive either SNS or FENIX™ MSA. Participants will be followed-up at 2 weeks post-surgery and at 6, 12 and 18months post-randomisation. The primary endpoint is success, as defined by device in use and ≥50 % improvement in the Cleveland Clinic Incontinence Score (CCIS) at 18 months post-randomisation. Secondary endpoints include complications, quality of life and cost effectiveness. Discussion: SaFaRI will rigorously evaluate a new technology for faecal incontinence, the FENIX™ MSA, allowing its safe and controlled introduction into current clinical practice. These results will inform the future surgical management of adult faecal incontinence.

Objective: to evaluate the clinical and costeffectiveness of a new blended dental contract incentivising improved oral health compared with a traditional dental contract based on units of dental activity (UDAs). Design: Non-randomised controlled study. Setting: Six UK primary care dental practices, three working under a new blended dental contract; three matched practices under a traditional contract. Participants: 550 new adult patients. Interventions: a new blended/incentive-driven primary care dentistry contract and service delivery model versus the traditional contract based on UDAs. Main outcome measures: Primary outcome was as follows: percentage of sites with gingival bleeding on probing. Secondary outcomes were as follows: extracted and filled teeth (%), caries (International Caries Detection and Assessment System (ICDAS)), oral health-related quality of life (Oral Health Impact Profile-14 (OHIP-14)). Incremental cost-effective ratios used OHIP-14 and quality adjusted life years (QALYs) derived from the EQ-5D-3L. Results: at 24 months, 291/550 (53%) patients returned for final assessment; those lost to follow-up attended 6.46 appointments on average (SD 4.80). The primary outcome favoured patients in the blended contract group. Extractions and fillings were more frequent in this group. Blended contracts were financially attractive for the dental provider but carried a higher cost for the service commissioner. Differences in generic health-related quality of life were negligible. Positive changes over time in oral health-related quality of life in both groups were statistically significant. Conclusions: This is the first UK study to assess the clinical and cost-effectiveness of a blended contract in primary care dentistry. Although the primary outcome favoured the blended contract, the results are limited because 47% patients did not attend at 24 months. This is consistent with 39% of adults not being regular attenders and 27% only visiting their dentist when they.

© the Author(s) 2015. Background. Retraction plays a vital role in optimizing the field of vision in minimal-access surgery. As such, a number of devices have been marketed to aid the surgeon in laparoscopic retraction. This systematic review explores the advantages and disadvantages of the different instruments in order to aid surgeons and their institutions in selecting the appropriate device. Primary outcome measures include operation time, length of stay, use of staff, patient morbidity, ease of use, conversion rates to open surgery, and cost. Methods. Systematic literature searches were performed in MEDLINE, EMBASE, the Cochrane Library, Current Controlled Trials, and ClinicalTrials.gov. The search strategy focused on studies testing a retraction device. The selection process was based on a predefined set of inclusion and exclusion criteria. Data were then extracted and analyzed. Results. Out of 1360 papers initially retrieved, 12 articles were selected for data extraction and analysis. A total of 10 instruments or techniques were tested. Devices included the Nathanson's liver retractor, liver suspension tape, the V-List technique, a silicone disk with or without a snake retractor, the Endoloop, the Endograb, a magnetic retractor, the VaroLift, a laparoscope holder, and a retraction sponge. None of the instruments reported were associated with increased morbidity. No studies found increased rates of conversion to open surgery. All articles reported that the tested instruments might spare the use of an assistant during the procedure. It was not possible to determine the impact on length of stay or operation time. Conclusions. Each analyzed device facilitates retraction, providing a good field of view while allowing reduced staff numbers and minimal patient morbidity. Due to economic and environmental advantages, reusable devices may be preferable to disposable instruments, although the choice must be primarily based on clinical judgement.

BACKGROUND: the COUGAR-02 trial recently showed survival and quality-of-life benefits of docetaxel and active symptom control (DXL + ASC) over active symptom control (ASC) alone in patients with refractory oesophagogastric adenocarcinoma. AIM: the aim of this study was to conduct an economic evaluation conforming to National Institute for Health and Care Excellence (NICE) technology appraisal guidance to evaluate the cost effectiveness of DXL + ASC versus ASC from the perspective of the English National Health Service (NHS). METHODS: Cost-utility analyses were conducted using trial data. Utility values were captured using the EQ-5D completed by patients at 3- and 6-weekly intervals, while resource use was captured using nurse-completed report forms and patient reports. Incremental cost-effectiveness ratios (ICERs) were calculated and the main outcome was cost per incremental quality-adjusted life-year (QALY). Nonparametric bootstrapping was conducted to capture sampling uncertainty and to generate a cost-effectiveness acceptability curve (CEAC). The analysis horizon was the trial period (median follow-up 12 months) and no modelling or discounting of future costs and benefits was conducted. RESULTS: Average costs were £9352 and £6218 for DXL + ASC and ASC, respectively, and average QALYs were 0.302 and 0.186, respectively. This yielded an ICER of £27,180 for DXL + ASC. DXL + ASC had a 24 % chance of being cost effective at a £20,000 QALY threshold (lambda) and a mean net monetary benefit of -£821; this rose to 59 % and £332 when the threshold was raised to £30,000. If NICE end-of-life criteria are applied, the probability of cost effectiveness increases to 90 % (at lambda = £50,000). Results were robust to sensitivity analyses. CONCLUSIONS: DXL + ASC is likely to be cost effective if an end-of-life premium is applied. Further research should determine the impact of different utility measurement strategies and different chemotherapy delivery modes on estimates of cost effectiveness.

© the Author 2016. Published by Oxford University Press on behalf of the British Geriatrics Society. Background and objectives: delirium is a distressing but potentially preventable condition common in older people in long-term care. It is associated with increased morbidity, mortality, functional decline, hospitalization and significant healthcare costs. Multicomponent interventions, addressing delirium risk factors, have been shown to reduce delirium by one-third in hospitals. It is not known whether this approach is also effective in long-term care. In previous work, we designed a bespoke delirium prevention intervention, called 'Stop Delirium!' in preparation for a definitive trial of Stop Delirium, we sought to address key aspects of trial design for the particular circumstances of care homes.Design: a cluster randomized feasibility study with an embedded process evaluation.Setting and participants: residents of 14 care homes for older people in one metropolitan district in the UK.Intervention: Stop Delirium!: a 16-month-enhanced educational package to support care home staff to address key delirium risk factors. Control homes received usual care.Measurements: we collected data to determine the following: recruitment and attrition; delirium rates and variability between homes; feasibility of measuring delirium, resource use, quality of life, hospital admissions and falls; and intervention implementation and adherence.Results: two-thirds (215) of eligible care home residents were recruited. One-month delirium prevalence was 4.0% in intervention and 7.1% in control homes. Proposed outcome measurements were feasible, although our approach appeared to underestimate delirium. Health economic evaluation was feasible using routinely collected data.Conclusion: a definitive trial of delirium prevention in long-term care is needed but will require some further design modifications and pilot work.

© 2015 John Wiley. &. Sons A/S. Published by John Wiley. &. Sons Ltd. Objectives to compare the cost-effectiveness of smoking cessation services in general dental practice (dental), general medical practice (GMP), pharmacy and NHS Stop Smoking Services (NHS SSS) from the perspective of the provider and the perspective of the NHS. Methods Retrospective monitoring data from NHS Bradford were accessed for any client attending a smoking cessation advisor within one of four commissioned smoking cessation services delivered by and within dental, GMP, pharmacy and NHS SSS (July 2011-December 2011). The treatment outcome of interest was 'quits' (effectiveness), and costs were assessed using incremental cost-effectiveness ratios (ICER) which compared each service setting against usual care (NHS SSS). All data were analysed using SPSS 19. Results for verified quits, only pharmacy services showed a lower mean cost per client and a higher proportion of CO verified quits than the other services. For both verified and self-reported quits dental services showed a slightly higher proportion of quits than NHS SSS; however, the mean cost per client was higher (£278.38 for an increase in quits of 1%). The GMP services were dominated by the NHS SSS, in as much as they were both less effective (a smaller proportion of quits and more expensive). This finding also holds true when we compared GMP services and pharmacy services. Conclusions from the perspective of the service provider and the NHS, the service considered to be 'cost-effective' when compared with 'usual care' (NHS SSS) was pharmacy services. This research has identified variations in service costs and effectiveness of services through the analysis of a pragmatic data set. Given the exploratory nature of this research, further research should explore the impact of service/location selection on uptake and cessation rates.

OBJECTIVE: We aim to describe the economic burden of UK cancer survivorship for breast, colorectal and prostate cancer patients treated with curative intent, 1 year post-diagnosis. METHODS: Patient-level data were collected over a 3-month period 12-15 months post-diagnosis to estimate the monthly societal costs incurred by cancer survivors. Self-reported resource utilisation data were obtained via the electronic Patient-reported Outcomes from Cancer Survivors system and included community-based health and social care, medications, travel costs and informal care. Hospital costs were retrieved through data linkage. Multivariate regression analysis was used to examine cost predictors. RESULTS: Overall, 298 patients were included in the analysis, including 136 breast cancer, 83 colorectal cancer and 79 prostate cancer patients. The average monthly societal cost was $ US 409 (95%CI: $ US 316-$ US 502) [mean: £ 260, 95%CI: £ 198-£ 322] and was incurred by 92% of patients. This was divided into costs to the National Health Service (mean: $ US 279, 95%CI: $ US 207-$ US 351) [mean: £ 177, 95%CI: £ 131-£ 224], patients' out-of-pocket (OOP) expenses (mean: $ US 40, 95%CI: $ US 15-$ US 65) [mean: £ 25, 95%CI: £ 9-£ 42] and the cost of informal care (mean: $ US 110, 95%CI: $ US 57-$ US 162) [mean: £ 70, 95%CI: £ 38-£ 102]. The distribution of costs was skewed with a small number of patients incurring very high costs. Multivariate analyses showed higher societal costs for breast cancer patients. Significant predictors of OOP costs included age and socioeconomic deprivation. CONCLUSIONS: This study found the economic burden of cancer survivorship is unevenly distributed in the population and that cancer survivors may still incur substantial costs over 1 year post-diagnosis. In addition, this study illustrates the feasibility of using an innovative online data collection platform to collect patient-reported resource utilisation information.

© 2014, the Author(s). Published by Routledge. Accurately documenting the occupational biographies of older people can be challenging given their lengthy duration and the complexity of contemporary employment. This paper shows how a traditionally quantitative occupational history calendar (OHC) instrument can be adapted for use in a mixed methods research design, to gather in-depth information about long working lives. The OHCs were embedded within semi-structured interviews and recorded lifetime work histories of between 33 and 53 years for 56 participants. Sequence analysis of the calendar data was undertaken in parallel to thematic analysis of interview transcripts. This included in-depth exploration of the factors motivating occupational changes and transitions and their impact in older age. Mixing methods allowed us to collate data over relatively long periods of time and enabled an examination of the complex interplay between work, family and personal circumstances that shapes employment histories. Selected research findings are used to demonstrate how this tool can effectively facilitate the exploration of long working lives.

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.

© 2015 Bagnall et al.; licensee BioMed Central. Background: Prisoners experience significantly worse health than the general population. This review examines the effectiveness and cost-effectiveness of peer interventions in prison settings. Methods: a mixed methods systematic review of effectiveness and cost-effectiveness studies, including qualitative and quantitative synthesis was conducted. In addition to grey literature identified and searches of websites, nineteen electronic databases were searched from 1985 to 2012. Study selection criteria were: Population: Prisoners resident in adult prisons and children resident in Young Offender Institutions (YOIs). Intervention: Peer-based interventions. Comparators: Review questions 3 and 4 compared peer and professionally led approaches. Outcomes: Prisoner health or determinants of health; organisational/process outcomes; views of prison populations. Study designs: Quantitative, qualitative and mixed method evaluations. Results: Fifty-seven studies were included in the effectiveness review and one study in the cost-effectiveness review; most were of poor methodological quality. Evidence suggested that peer education interventions are effective at reducing risky behaviours, and that peer support services are acceptable within the prison environment and have a positive effect on recipients, practically or emotionally. Consistent evidence from many, predominantly qualitative, studies, suggested that being a peer deliverer was associated with positive effects. There was little evidence on cost-effectiveness of peer-based interventions. Conclusions: There is consistent evidence from a large number of studies that being a peer worker is associated with positive health; peer support services are also an acceptable source of help within the prison environment and can have a positive effect on recipients. Research into cost-effectiveness is sparse. Systematic review registration: PROSPERO ref: CRD42012002349.

Introduction: Outpatient parenteral antimicrobial therapy (OPAT) is used to treat a wide range of infections, and is common practice in countries such as the USA and Australia. In the UK, national guidelines (standards of care) for OPAT services have been developed to act as a benchmark for clinical monitoring and quality. However, the availability of OPAT services in the UK is still patchy and until quite recently was available only in specialist centres. Over time, National Health Service (NHS) Trusts have developed OPAT services in response to local needs, which has resulted in different service configurations and models of care. However, there has been no robust examination comparing the cost-effectiveness of each service type, or any systematic examination of patient preferences for services on which to base any business case decision. Methods and analysis: the study will use a mixed methods approach, to evaluate patient preferences for and the cost-effectiveness of OPAT service models. The study includes seven NHS Trusts located in four counties. There are five inter-related work packages: a systematic review of the published research on the safety, efficacy and cost-effectiveness of intravenous antibiotic delivery services; a qualitative study to explore existing OPAT services and perceived barriers to future development; an economic model to estimate the comparative value of four different community intravenous antibiotic services; a discrete choice experiment to assess patient preferences for services, and an expert panel to agree which service models may constitute the optimal service model(s) of community intravenous antibiotics delivery. Ethics and dissemination: the study has been approved by the NRES Committee, South West-Frenchay using the Proportionate Review Service (ref 13/SW/0060). The results of the study will be disseminated at national and international conferences, and in international journals.

BACKGROUND: the rising financial burden of cancer on health-care systems worldwide has led to the increased demand for evidence-based research on which to base reimbursement decisions. Economic evaluations are an integral component of this necessary research. Ascertainment of reliable health-care cost and quality-of-life estimates to inform such studies has historically been challenging, but recent advances in informatics in the United Kingdom provide new opportunities. METHODS: the costs of hospital care for breast, colorectal and prostate cancer disease-free survivors were calculated over 15 months from initial diagnosis of cancer using routinely collected data within a UK National Health Service (NHS) Hospital Trust. Costs were linked at patient level to patient-reported outcomes and registry-derived sociodemographic factors. Predictors of cost and the relationship between costs and patient-reported utility were examined. RESULTS: the study population included 223 breast cancer patients, 145 colorectal and 104 prostate cancer patients. The mean 15-month cumulative health-care costs were £12 595 (95% CI £11 517-£13 722), £12 643 (£11 282-£14 102) and £3722 (£3263-£4208), per-patient respectively. The majority of costs occurred within the first 6 months from diagnosis. Clinical stage was the most important predictor of costs for all cancer types. EQ-5D score was predictive of costs in colorectal cancer but not in breast or prostate cancer. CONCLUSION: it is now possible to evaluate health-care cost using routine NHS data sets. Such methods can be utilised in future retrospective and prospective studies to efficiently collect economic data.

BACKGROUND: Mechanical chest compression devices have the potential to help maintain high-quality cardiopulmonary resuscitation (CPR), but despite their increasing use, little evidence exists for their effectiveness. We aimed to study whether the introduction of LUCAS-2 mechanical CPR into front-line emergency response vehicles would improve survival from out-of-hospital cardiac arrest. METHODS: the pre-hospital randomised assessment of a mechanical compression device in cardiac arrest (PARAMEDIC) trial was a pragmatic, cluster-randomised open-label trial including adults with non-traumatic, out-of-hospital cardiac arrest from four UK Ambulance Services (West Midlands, North East England, Wales, South Central). 91 urban and semi-urban ambulance stations were selected for participation. Clusters were ambulance service vehicles, which were randomly assigned (1:2) to LUCAS-2 or manual CPR. Patients received LUCAS-2 mechanical chest compression or manual chest compressions according to the first trial vehicle to arrive on scene. The primary outcome was survival at 30 days following cardiac arrest and was analysed by intention to treat. Ambulance dispatch staff and those collecting the primary outcome were masked to treatment allocation. Masking of the ambulance staff who delivered the interventions and reported initial response to treatment was not possible. The study is registered with Current Controlled Trials, number ISRCTN08233942. FINDINGS: We enrolled 4471 eligible patients (1652 assigned to the LUCAS-2 group, 2819 assigned to the control group) between April 15, 2010 and June 10, 2013. 985 (60%) patients in the LUCAS-2 group received mechanical chest compression, and 11 (

© 2015 Young et al. Background: Delirium is the most frequent complication among older people following hospitalisation. Delirium may be prevented in about one-third of patients using a multicomponent intervention. However, in the United Kingdom, the National Health Service has no routine delirium prevention care systems. We have developed the Prevention of Delirium Programme, a multicomponent delirium prevention intervention and implementation process. We have successfully carried out a pilot study to test the feasibility and acceptability of implementation of the programme. We are now undertaking preliminary testing of the programme. Methods/Design: the Prevention of Delirium Study is a multicentre, cluster randomised feasibility study designed to explore the potential effectiveness and cost-effectiveness of the Prevention of Delirium Programme. Sixteen elderly care medicine and orthopaedic/trauma wards in eight National Health Service acute hospitals will be randomised to receive the Prevention of Delirium Programme or usual care. Patients will be eligible for the trial if they have been admitted to a participating ward and are aged 65 years or over. The primary objectives of the study are to provide a preliminary estimate of the effectiveness of the Prevention of Delirium Programme as measured by the incidence of new onset delirium, assess the variability of the incidence of new-onset delirium, estimate the intracluster correlation coefficient and likely cluster size, assess barriers to the delivery of the Prevention of Delirium Programme system of care, assess compliance with the Prevention of Delirium Programme system of care, estimate recruitment and follow-up rates, assess the degree of contamination due to between-ward staff movements, and investigate differences in financial costs and benefits between the Prevention of Delirium Programme system of care and standard practice. Secondary objectives are to investigate differences in the number, severity and length of delirium episodes (including persistent delirium); length of stay in hospital; in-hospital mortality; destination at discharge; health-related quality of life and health resource use; physical and social independence; anxiety and depression; and patient experience. Discussion: This feasibility study will be used to gather data to inform the design of a future definitive randomised controlled trial.

© 2015 Walwyn et al. Background: Individuals with a learning disability (LD) are at higher risk of developing type 2 diabetes, but LD is not straightforward to define or identify, especially at the milder end of the spectrum, which makes case finding difficult. While supported self-management of health problems is now established, current material is largely educational and didactic with little that facilitates behavioural change. The interaction between the person with diabetes and others supporting their care is also largely unknown. For these reasons, there is considerable work needed to prepare for a definitive trial. The aim of this paper is to publish the abridged protocol of this preparatory work. Methods/Design: Phase I is a prospective case-finding study (target n = 120 to 350) to identify and characterise potential participants, while developing a standardised supported self-management intervention. Phase II is a randomised feasibility trial (target n = 80) with blinded outcome assessment. Patients identified in Phase I will be interviewed and consented prior to being randomised to (1) standard treatment, or (2) supported self-management. Both arms will also be provided with an 'easy read' accessible information resource on managing type 2 diabetes. The intervention will be standardised but delivered flexibly depending on patient need, including components for the participant, a supporter, and shared activities. Outcomes will be (i) robust estimates of eligibility, consent and recruitment rates with refined recruitment procedures; (ii) characterisation of the eligible population; (iii) a standardised intervention with associated written materials, (iv) adherence and negative outcomes measures; (v) preliminary estimates of adherence, acceptability, follow-up and missing data rates, along with refined procedures; and (vi) description of standard treatment. Discussion: Our study will provide important information on the nature of type 2 diabetes in adults with LD living in the community, on the challenges of identifying those with milder LD, and on the possibilities of evaluating a standardised intervention to improve self-management in this population.

© 2013 the Authors. Objective to describe the diet costs of adults in the National Diet and Nutrition Study (NDNS) and explore patterns in costs according to sociodemographic indicators. Design Cross-sectional diet diary information was matched to a database of food prices to assign a cost to each food or non-alcoholic beverage consumed. Daily diet costs were calculated, as well as costs per 10 MJ to improve comparability across differing energy requirements. Costs were compared between categories of sociodemographic variables and health behaviours. Multivariable regression assessed the effects of each variable on diet costs after adjustment. Setting the NDNS is a rolling dietary survey, recruiting a representative UK sample each year. The study features data from 2008-2010. Subjects Adults aged 19 years or over were included. The sample consisted of 1014 participants. Results the geometric mean daily diet cost was £2·89 (95 % CI £2·81, £2·96). Energy intake and daily diet cost were strongly associated. The mean energy-adjusted cost was £4·09 (95 % CI £4·01, £4·18) per 10 MJ. Energy-adjusted costs differed significantly between many subgroups, including by sex and household income. Multivariable regression found significant effects of sex, qualifications and occupation (costs per 10 MJ only), as well as equivalized household income, BMI and fruit and vegetable consumption on diet costs. Conclusions This is the first time that monetary costs have been applied to the diets of NDNS adults. The findings suggest that certain subgroups in the UK-for example those on lower incomes-consume diets of lower monetary value. Observed differences were mostly in the directions anticipated.

Objectives There is continuing demand for non-implant prosthodontic treatment and yet there is a paucity of high quality Randomised Controlled Trial (RCT) evidence for best practice. The aim of this research was to provide evidence for best practice in prosthodontic impressions by comparing two impression materials in a double-blind, randomised, crossover, controlled, clinical trial. Methods Eighty-five patients were recruited, using published eligibility criteria, to the trial at Leeds Dental Institute, UK. Each patient received two sets of dentures; made using either alginate or silicone impressions. Randomisations determined the order of assessment and order of impressions. The primary outcome was patient blinded preference for unadjusted dentures. Secondary outcomes were patient preference for the adjusted dentures, rating of comfort, stability and chewing efficiency, experience of each impression, and an OHIP-EDENT questionnaire. Results Seventy-eight (91.8%) patients completed the primary assessment. 53(67.9%) patients preferred dentures made from silicone impressions while 14(17.9%) preferred alginate impressions. 4(5.1%) patients found both dentures equally satisfactory and 7 (9.0%) found both equally unsatisfactory. There was a 50% difference in preference rates (in favour of silicone) (95%CI 32.7-67.3%, p < 0.0001). Conclusion There is significant evidence that dentures made from silicone impressions were preferred by patients. Clinical significance Given the strength of the clinical findings within this paper, dentists should consider choosing silicone rather than alginate as their material of choice for secondary impressions for complete dentures. Trial Registration: ISRCTN 01528038. This article forms part of a project for which the author (TPH) won the Senior Clinical Unilever Hatton Award of the International Assocation for Dental Research, Capetown, South Africa, June 2014. © 2014 the Authors.

Objective the aim of this study was to assess the cost effectiveness of silicone and alginate impressions for complete dentures. Methods Cost effectiveness analyses were undertaken alongside a UK single centre, double blind, controlled, crossover clinical trial. Taking the perspective of the healthcare sector, effectiveness is measured using the EuroQol (EQ-5D-3L) which provides a single index value for health status that may be combined with time to produce quality adjusted life years (QALYs); and Oral Health Impact Profile (OHIP-EDENT). Incremental cost effectiveness ratios are presented representing the additional cost per one unit gained. Results Mean cost was higher in the silicone impression group (£388.57 vs. £363.18). Negligible between-group differences were observed in QALY gains; the silicone group had greater mean OHIP-EDENT gains. The additional cost using silicone was £3.41 per change of one point in the OHIP-EDENT. Conclusions the silicone group was more costly, driven by the cost of materials. Changes in the EQ-5D and QALY gains over time and between arms were not statistically significant. Change in OHIP-EDENT score showed greater improvement in the silicone group and the difference between arms was statistically significant. Given negligible QALY gains and low level of resource use, results must be treated with caution. It is difficult to make robust claims about the comparative cost-effectiveness. Clinical significance Silicone impressions for complete dentures improve patients' quality of life (OHIP-EDENT score). The extra cost of silicone impressions is £30 per patient. Dentists, patients and health care funders need to consider the clinical and financial value of silicone impressions. Different patients, different dentists, different health funders will have individual perceptions and judgements. ISRCTN01528038. NIHR-RfPB grant PB-PG-0408-16300. This article forms part of a project for which the author (TPH) won the Senior Clinical Unilever Hatton Award of the International Assocation for Dental Research, Capetown, South Africa, June 2014. © 2014 the Authors.

Abstract As providers of health care, we face increasing demand on our limited, indeed diminishing, resources. Economic appraisal of our interventions means assessing the trade-off between effectiveness, efficiency and equity. When rationing becomes inevitable, calculation of utility values is a valuable decision-making tool. This paper reviews objective measures of patient benefit, such as quality of life, and focuses on their application within otolaryngology. © JLO (1984) Limited 2014.

BACKGROUND: Delirium (or acute confusion) is a serious illness common in older people, in which a person's thinking and perceptions may be affected. Reducing delirium is important because of the considerable distress it causes, and the poor outcomes associated with it, such as increased admissions to hospital, falls, mortality and costs to the National Health Service (NHS). Preventing delirium is possible using multicomponent interventions; successful interventions in hospitals have reduced it by one-third. However, there is little research to guide practice in care homes, where it is common because of the clustering of known risk factors (older age, frailty, and dementia). In previous work we developed a multicomponent intervention to prevent delirium in care homes, called Stop Delirium! the intervention was based upon evidence from the research literature relating to the prevention of delirium and on strategies to change professional practice. Before starting a large costly trial of Stop Delirium!, this pilot study will test and help improve the design and feasibility of the trial protocol. METHODS/DESIGN: We plan to conduct a cluster randomised pilot trial in 14 care homes (independent residential and nursing). Following recruitment of residents (over 60 years, consenting or with consultee agreement, able to communicate in English, and not in palliative care) participating homes will be randomised, stratified by size of home and proportion of residents with dementia. Stop Delirium! will be delivered to intervention homes over 16 months, with controls receiving usual care. The primary outcome measure will be the presence of delirium on any day during a one-month post-intervention period.We will collect data to determine 1) recruitment and attrition rates, 2) feasibility of various outcomes measurements, and 3) feasibility of capturing health resource use (resident diaries and by examining health records). We will estimate the between-cluster variation for the primary outcome, delirium occurrence. DISCUSSION: This pilot study will refine methods for the definitive trial. The lessons learnt will also contribute to implementing National Institute for Health and Clinical Excellence (NICE) delirium guidelines, which recommend multicomponent interventions for delirium prevention. TRIAL REGISTRATION: ISRCTN27972532.

BACKGROUND: Rheumatoid Arthritis (RA) is one of the most common autoimmune diseases, affecting approximately 1% of the UK adult population. Patients suffer considerable pain, stiffness and swelling and can sustain various degrees of joint destruction, deformity, and significant functional decline. In addition, the economic burden due to hospitalisation and loss of employment is considerable, with over 50% of patients being work-disabled within 10 years of diagnosis. Despite several biologic disease modifying anti-rheumatic drugs (bDMARD) now available, there is a lack of data to guide biologic sequencing. In the UK, second-line biologic treatment is restricted to a single option, rituximab. The aim of the SWITCH trial is to establish whether an alternative-mechanism-TNF-inhibitor (TNFi) or abatacept are as effective as rituximab in patients with RA who have failed an initial TNFi drug. METHODS/DESIGN: SWITCH is a pragmatic, phase IV, multi-centre, parallel-group design, open-label, randomised, controlled trial (RCT) comparing alternative-mechanism-TNFi and abatacept with rituximab in patients with RA who have failed an initial TNFi drug. Participants are randomised in a 1:1:1 ratio to receive alternative mechanism TNFi, (monoclonal antibodies: infliximab, adalimumab, certolizumab or golimumab or the receptor fusion protein, etanercept), abatacept or rituximab during the interventional phase (from randomisation up to week 48). Participants are subsequently followed up to a maximum of 96 weeks, which constitutes the observational phase. The primary objective is to establish whether an alternative-mechanism-TNFi or abatacept are non-inferior to rituximab in terms of disease response at 24 weeks post randomisation. The secondary objectives include the comparison of alternative-mechanism-TNFi and abatacept to rituximab in terms of disease response, quality of life, toxicity, safety and structural and bone density outcomes over a 12-month period (48 weeks) and to evaluate the cost-effectiveness of switching patients to alternative active therapies compared to current practice. DISCUSSION: SWITCH is a well-designed trial in this therapeutic area that aims to develop a rational treatment algorithm to potentially inform personalised treatment regimens (as opposed to switching all patients to only one available (and possibly unsuccessful) therapy), which may lead to long-term improved patient outcomes and gains in population health. TRIAL REGISTRATION: UKCRN Portfolio ID: 12343; ISRCTN89222125 ; NCT01295151.

INTRODUCTION: in England, in 2006, new dental contracts devolved commissioning of dental services locally to Primary Care Trusts to meet the needs of their local population. The new national General Dental Services contracts (nGDS) were based on payment for Units of Dental Activity (UDAs) awarded in three treatment bands based on complexity of care. Recently, contract currency in UK dentistry is evolving from UDAs based on volume and case complexity towards 'blended contracts' that include incentives linked with key performance indicators such as quality and improved health outcome. Overall, evidence of the effectiveness of incentive-driven contracting of health providers is still emerging. The INCENTIVE Study aims to evaluate a blended contract model (incentive-driven) compared to traditional nGDS contracts on dental service delivery in practices in West Yorkshire, England. METHODS AND ANALYSIS: the INCENTIVE model uses a mixed methods approach to comprehensively evaluate a new incentive-driven model of NHS dental service delivery. The study includes 6 dental surgeries located across three newly commissioned dental practices (blended contract) and three existing traditional practices (nGDS contracts). The newly commissioned practices have been matched to traditional practices by deprivation index, age profile, ethnicity, size of practice and taking on new patients. The study consists of three interlinked work packages: a qualitative study to explore stakeholder perspectives of the new service delivery model; an effectiveness study to assess the INCENTIVE model in reducing the risk of and amount of dental disease and enhance oral health-related quality of life in patients; and an economic study to assess cost-effectiveness of the INCENTIVE model in relation to clinical status and oral health-related quality of life. ETHICS AND DISSEMINATION: the study has been approved by NRES Committee London, Bromley. The results of this study will be disseminated at national and international conferences and in international journals.

BACKGROUND: Primary Sjögren's Syndrome (PSS) mainly affects women (9:1 female:male ratio) and is one of the commonest autoimmune diseases with a prevalence of 0.1 - 0.6% of adult women. For patients with PSS there is currently no effective therapy that can alter the progression of the disease. The aim of the TRACTISS study is to establish whether in patients with PSS, treatment with rituximab improves clinical outcomes. METHODS/DESIGN: TRACTISS is a UK multi-centre, double-blind, randomised, controlled, parallel group trial of 110 patients with PSS. Patients will be randomised on a 1:1 basis to receive two courses of either rituximab or placebo infusion in addition to standard therapy, and will be followed up for up to 48 weeks. The primary objective is to assess the extent to which rituximab improves symptoms of fatigue and oral dryness. Secondary outcomes include ocular dryness, salivary flow rates, lacrimal flow, patient quality of life, measures of disease damage and disease activity, serological and peripheral blood biomarkers, and glandular histology and composition. DISCUSSION: the TRACTISS trial will provide direct evidence as to whether rituximab in patients with PSS leads to an improvement in patient symptoms and a reduction in disease damage and activity. TRIAL REGISTRATION: UKCRN Portfolio ID: 9809 ISRCTN65360827.

Primary care referral to commercial weight loss programmes that follow best practice is included in current UK guidance on the management of adult obesity. This study investigated whether such a programme was cost-effective compared with usual care. A decision-analytical Markov model was developed to estimate the lifetime costs and benefits of the referral programme compared with usual care and enable a cost-utility analysis. The model cohort transited between body mass index classifications and type 2 diabetes, stroke and myocardial infarction (MI) with risk, cost and effect parameter values taken from published literature. The cost per incremental quality-adjusted life year (QALY) was calculated. Extensive deterministic and scenario sensitivity analyses and probabilistic sensitivity analyses (PSA) were conducted. At 12 months, the incremental cost-effectiveness ratio was £6906, indicating that programme referral was cost-effective. Over a lifetime, referral to the commercial programme was dominant as it led to a cost saving of £924 and conferred incremental benefit (0.22 QALY) over usual care. Model simulations estimated lower lifetime rates of type 2 diabetes, stroke and MI as a result of the weight loss achieved. The results were robust to extensive sensitivity analyses. The PSA indicated that programme referral had a 68% chance of being cost-effective at a willingness to pay per incremental QALY threshold of £20,000. Referral to the programme dominated usual care, being both cheaper and more effective. These results compare favourably with economic evaluations of other obesity interventions and add to a growing evidence base on the cost-effectiveness of commercial weight loss providers and practices.

CONTEXT: Both positive and negative results have been reported in the literature from the use of acupressure at the P6 point, providing evidence of highly suggestive but not conclusive results. OBJECTIVES: to clarify whether acupressure is effective in the management of chemotherapy-related nausea and vomiting. METHODS: a randomized, three-group, sham-controlled trial was designed. Patients with cancer receiving chemotherapy were randomized to receive standardized antiemetics and acupressure wristbands, sham acupressure wristbands, or antiemetics alone. Primary outcome assessment (nausea) was carried out daily for seven days per chemotherapy cycle over four cycles. Secondary outcomes included vomiting, psychological distress, and quality of life. RESULTS: Five hundred patients were randomized. Primary outcome analysis (nausea in Cycle 1) revealed no statistically significant differences between the three groups, although nausea levels in the proportion of patients using wristbands (both real and sham) were somewhat lower than those in the proportion of patients using antiemetics-only group. Adjusting for gender, age, and emetic risk of chemotherapy, the odds ratio of lower nausea experience was 1.18 and 1.42 for the acupressure and sham acupressure groups, respectively. A gender interaction effect was evident (P = 0.002). No significant differences were detected in relation to vomiting, anxiety, and quality-of-life measures. CONCLUSION: No clear recommendations can be made about the use of acupressure wristbands in the management of chemotherapy-related nausea and vomiting as results did not reach statistical significance. However, the study provided evidence of encouraging signals in relation to improved nausea experience and warrants further consideration in both practice and further clinical trials. TRIAL REGISTRATION: This trial is registered with the ISRCT register, number ISRCTN87604299.

Background: a healthy diet is important to promote health and well-being while preventing chronic disease. However, the monetary cost of consuming such a diet can be a perceived barrier. This study will investigate the cost of consuming a range of dietary patterns. Methods: a cross-sectional analysis, where cost of diet was assigned to dietary intakes recorded using a Food Frequency Questionnaire. A mean daily diet cost was calculated for seven data-driven dietary patterns. These dietary patterns were given a healthiness score according to how well they comply with the UK Department of Health's Eatwell Plate guidelines. This study involved ~35 000 women recruited in the 1990s into the UK Women's Cohort Study. Results: a significant positive association was observed between diet cost and healthiness of the diet (p for trend > 0.001). The healthiest dietary pattern was double the price of the least healthy, £6.63/day and £3.29/day, respectively. Dietary diversity, described by the patterns, was also shown to be associated with increased cost. Those with higher education and a professional or managerial occupation were more likely to consume a healthier diet. Conclusions: a healthy diet is more expensive to the consumer than a less healthy one. In order to promote health through diet and reduce potential inequalities in health, it seems sensible that healthier food choices should be made more accessible to all.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a major cause of mortality in intensive care patients and lacks effective treatments. A previous randomised controlled Phase II trial suggested that an intravenous (i.v.) infusion of salbutamol may be beneficial, as it reduced extravascular lung water and plateau airway pressure. The Beta-Agonist Lung injury TrIal-2 (BALTI-2) was initiated to evaluate the effects of this intervention on mortality in patients with ARDS. OBJECTIVES: to evaluate whether or not, in patients with ARDS, an i.v. infusion of salbutamol given at 15 μg/kg ideal body weight (IBW)/hour for up to 7 days, compared with a placebo (0.9% sodium chloride) infusion, reduces 28-day all-cause mortality and other clinical outcomes. To evaluate salbutamol's clinical effectiveness and its cost-effectiveness in subgroups of patients. DESIGN: a multicentre, randomised, placebo-controlled trial. SETTING: Forty-six intensive care units (ICUs) in the UK. PARTICIPANTS: Patients were eligible if they (1) were intubated and mechanically ventilated patients in participating ICUs; (2) were within 72 hours of onset of ARDS; (3) fulfilled American-European Consensus Conference definition for ARDS {acute-onset, severe hypoxaemic respiratory failure [partial pressure of oxygen in arterial blood/fraction of inspired oxygen ≤ 26.7 kPa (200 mmHg)] and bilateral infiltrates on the chest radiograph in the absence of clinical evidence of left atrial hypertension}; and (4) were aged ≥ 16 years. INTERVENTIONS: Intravenous infusion of salbutamol (15 μg/kg IBW/hour) or placebo (0.9% saline) for up to 7 days. MAIN OUTCOME MEASURES: All-cause mortality 28 days after randomisation, mortality at (first) discharge from ICU, mortality at (first) discharge from hospital, number of ventilator-free days, number of organ failure-free days, mortality at 12 months post randomisation, side effects (tachycardia/new arrhythmia/lactic acidosis) sufficient to stop treatment with trial drug, health-related quality of life (European Quality of Life-5 Dimensions and Short Form questionnaire-12 items at 6 and 12 months after randomisation), length of stay in critical care unit and length of stay in hospital. RESULTS: Forty-six ICUs recruited patients to the trial. A total of 326 patients were randomised; 162 were allocated to salbutamol and 164 to placebo. One patient in each group withdrew consent. Recruitment was stopped after the second interim analysis because of safety concerns. Salbutamol increased 28-day mortality: 55 (34%) of 161 patients died in the salbutamol group compared with 38 (23%) of 163 in the placebo group (risk ratio 1.47, 95% confidence interval 1.03 to 2.08). CONCLUSIONS: Treatment with i.v. salbutamol early in the course of ARDS was poorly tolerated, is unlikely to be beneficial and could worsen outcomes. Further trials of β-agonists in patients with ARDS are unlikely to be conducted. Some questions remain, such as whether or not there may be benefit at a different dose or in specific populations, but any studies investigating these would require a very strong rationale. TRIAL REGISTRATION: Current Controlled Trials ISRCTN38366450. FUNDING: the National Institute for Health Research Health Technology Assessment programme.

BACKGROUND/OBJECTIVES: Diet cost could influence dietary patterns, with potential health consequences. Assigning a monetary cost to diet is challenging, and there are contrasting methods in the literature. This study compares two methods-a food cost database linked to 4-day diet diaries and an individual cost calculated from household till receipts. SUBJECTS/METHODS: the Diet and Nutrition Tool for Evaluation (DANTE) had supermarket prices (cost per 100 g) added to its food composition table. Agreement between diet costs calculated using DANTE from food diaries and expenditure recorded using food purchase till receipts for 325 individuals was assessed using correlation and Bland Altman (BA) plots. RESULTS: the mean difference between the methods' estimates was £0.10. The BA showed 95% limits of agreement of £2.88 and -£3.08. Excluding the highest 5% of diet cost values from each collection method reduced the mean difference to £0.02, with limits of agreement ranging from £2.31 to -£2.35. Agreement between the methods was stronger for males and for adults. CONCLUSIONS: Diet cost estimates using a food price database with 4-day food diaries are comparable to recorded expenditure from household till receipts at the population or group level. At the individual level, however, estimates differed by as much as £3.00 per day. The methods agreed less when estimating diet costs of children, females or those with more expensive diets.

Objective. To evaluate an information needs questionnaire that uses a Thurstone's paired comparison approach to measure the information needs of patients with chronic kidney disease. Methods. A two-phased, cross-sectional survey that sequentially develops and tests the questionnaire. Semi-structured interviews (n=20) generated information needs items for inclusion in the questionnaire. These items were paired using Ross's matrix. The questionnaire was used in interviews in phase two (n=89) and paired comparison analysis was undertaken. Results. A majority of patients ranked highly self-care information, how to manage their own condition, better control their diet and fluid intake, and understand blood results. 70.79% of patients agreed all items in the questionnaire to be relevant; there was an acceptable degree of reliability for data scalability (R2 =0.6175); agreement found between patients (Kendall's coefficient 0.06, p

Purpose - the purpose of this paper is to provide insights on the relationship between health and employment in older age. Design/methodology/ approach - Qualitative methods are used with some additional quantitative analysis to explore emergent themes. The qualitative analysis is based on interviews with 56 men and women between the ages of 50 and 68. This part of the study uses the respondents' own words to explain how physical and mental ill-health has impacted on labour market participation and vice versa. The quantitative analysis uses data from the British Household Panel Study and multivariate techniques. Findings - the research highlights the complexity, individuality and two-way causality underlying the relationships between health, work and worklessness in older age. The analysis also suggests that type of job and workplace conditions matter. The negative impact of the onset of ill-health on employment participation only appears to be accentuated by age for women. Research limitations/implications - the two data sets are not directly comparable. Social implications - Planned rises in the age at which state pensions are payable need to be accompanied by policies that improve the health of older people and changes in workplace practices that facilitate longer working lives. Originality/value - the paper has a specific focus on the relationship between ill-health and employment in older age; uses qualitative methods to draw out the main issues and quantitative analysis to draw additional insights and make some comparisons with younger cohorts. © Emerald Group Publishing Limited.

BACKGROUND: There are over 25 million people worldwide living with or beyond cancer and this number is increasing. Cancer survivors face a range of problems following primary treatment. One of the most frequently reported and distressing symptoms experienced by cancer survivors is fatigue. There is growing support for survivors who are experiencing problems after cancer treatment to engage in supported self-management. To date there is some evidence of effective interventions to manage fatigue in this population; however, to our knowledge there are no online resources that draw on this information to support self-management of fatigue. This paper describes the protocol for an exploratory randomized controlled trial of an online intervention to support self-management of cancer-related fatigue after primary cancer treatment. METHODS/DESIGN: This is a parallel-group two-armed (1:1) exploratory randomized controlled trial including 125 cancer survivors experiencing fatigue (scoring ≥4 on a unidimensional 11-point numeric rating scale for fatigue intensity) within five years of primary treatment completion with curative intent. Participants will be recruited from 13 NHS Trusts across the UK and randomized to either the online intervention (RESTORE), or a leaflet comparator (Macmillan Cancer Backup, Coping with Fatigue). The primary outcome is a change in Perceived Self-Efficacy for Fatigue Self-Management (as measured by the Perceived Self-Efficacy for Fatigue Self-Management Instrument). Secondary outcomes include impact on perception and experience of fatigue (measured by the Brief Fatigue Inventory), and quality of life (measured by the Functional Assessment of Cancer Therapy - General and the Personal Wellbeing Index). Outcome measures will be collected at baseline, 6 weeks (completion of intervention), and 3 months. Process evaluation (including telephone interviews with recruiting staff and participants) will determine acceptability of the intervention and trial processes. DISCUSSION: Data from this trial will be used to refine the intervention and contribute to the design of an effectiveness trial. This intervention will be expanded to address other cancer-related problems important to cancer survivors following primary cancer treatment. TRIAL REGISTRATION: ISRCTN67521059.

The mortality from breast cancer has improved steadily over the past two decades, in part because of the increased use of more effective adjuvant therapies. Thousands of women are routinely treated with intensive chemotherapy, which can be unpleasant, is expensive and is occasionally hazardous. Oncologists have long known that some of these women may not need treatment, either because they have a low risk of relapse or because they have tumour biology that makes them less sensitive to chemotherapy and more suitable for early adjuvant endocrine therapy. There is an urgent need to improve patient selection so that chemotherapy is restricted to those patients who will benefit from it. Here we review the emerging technologies that are available for improving patient selection for chemotherapy. We describe the OPTIMA trial, which has just opened to recruitment in the UK, is the latest addition to trials in this area, and is the first to focus on the relative cost-effectiveness of alternate predictive assays.

BACKGROUND: Chronic back pain continues to be a costly and prevalent condition. The latest NICE guidelines issued in 2009 state that for patients with persistent back pain (of between six weeks and twelve months duration), who are highly distressed and/or disabled and for whom exercise, manual therapy and acupuncture has not been beneficial, the evidence supports a combination of around 100 hours of combined physical and psychological treatment. This is costly, and may prove unacceptable to many patients. A key recommendation of these guidelines was for further randomised controlled trials (RCTs) of psychological treatment and to target treatment to specific sub-groups of patients. Recent trials that have included psychological interventions have shown only moderate improvement at best, and results are not maintained long term. There is therefore a need to test theoretically driven interventions that focus on specific high-risk sub-groups, in which the intervention is delivered at full integrity against a credible control. METHODS/DESIGN: a feasibility study of a pragmatic randomised controlled trial comparing psychologist-delivered Contextual Cognitive Behavioural Therapy (CCBT) against Treatment As Usual (TAU) physiotherapy delivered by physiotherapists for the treatment of chronic lower back pain in 'avoidant' patients. Ninety-two patients referred for physiotherapy will be recruited and randomised on a 1:1 basis to receive CCBT or TAU. Treatment groups will be balanced by centre and pain interference score. Primary outcomes include assessing the credibility and acceptability of the intervention, and to demonstrate proof of principle through a greater change in pain acceptance in the CCBT arm, measured by the Acceptance and Action -II and the Chronic Pain Acceptance questionnaires. In addition, the feasibility of carrying out a full trial will be explored with reference to recruitment and follow-up rates including the assessment of the burden of outcome measure completion. Secondary patient outcomes include disability, pain, fear of movement, mood, quality of life, and global recovery. Outcomes are measured at three and six months post-randomisation. DISCUSSION: This paper details the rationale, design, therapist training system and recruitment methods to be used in a feasibility study which will inform the design and efficient implementation of a future definitive RCT. TRIAL REGISTRATION: ISRCTN43733490.

BACKGROUND: Psoriatic arthritis (PsA) is estimated to occur in 10-15% of people with psoriasis and accounts for 13% of people attending early arthritis clinics. With an increasing awareness of the poor outcomes associated with PsA and the availability of new effective, but costly, treatments, there is an urgent need to research the optimal treatment for patients with PsA. The aim of the TICOPA study is to establish whether, in treatment naive early PsA patients, "tight control" intensive management with protocol driven therapies and pre-defined objective targets for treatment can improve clinical outcome compared to standard care alone. METHODS/DESIGN: TICOPA is a UK multicentre, open-label, randomised controlled, parallel group trial of 206 patients with early PsA. Patients will be randomised on a 1:1 basis to receive either standard care (12 weekly review) or intensive management (4 weekly review) for a period of 48 weeks. Patients assigned to the intensive management group will follow a strict treatment protocol whereby dose continuation/escalation is determined through the objective assessment of the minimal disease activity (MDA) criteria. Patients assigned to the standard care group will have treatment prescribed as felt appropriate by the treating clinician, with no set protocol. The primary objective of the trial is to compare intensive management with standard care in terms of the proportion of patients achieving an ACR 20 response at 48 weeks post-randomisation, in order to determine whether intensive management has superior clinical efficacy. Key secondary outcomes include ACR 50 and 70, PASI 75 and X-ray Van der Heijde score at 48 weeks post-randomisation along with cost-effectiveness at 12, 24 and 28 weeks. DISCUSSION: the TICOPA trial will provide direct evidence as to whether the use of early and intensive treatment in PsA in routine clinical care leads to an improvement in patients' disease activity and a reduction in radiological joint damage. TRIAL REGISTRATION: ISRCTN30147736, NCT01106079.

OBJECTIVE: to determine the cost-effectiveness of transcatheter aortic valve implantation (TAVI) compared with surgical aortic valve replacement (SAVR) in a high-risk aortic stenosis (AS) population. DESIGN: a cost-utility analysis employing the National Institute of Clinical Excellence (NICE) reference case design for technology appraisals. SETTING: the perspective of the UK National Health Service. PATIENTS: Utility data from a UK high-risk AS population. TAVI and SAVR effectiveness was taken from the PARTNER a randomised controlled trial. MAIN OUTCOME MEASURES: Costs modelled over a 10 year horizon using a Markov model. Incremental cost-effectiveness ratios and cost-effectiveness acceptability curve were calculated with reference to the NICE willingness to pay per quality adjusted life year (QALY) gain threshold. Deterministic and probabilistic sensitivity analyses performed. RESULTS: Despite greater procedural costs (£16 500 vs £9,256), TAVI was cost-effective compared with SAVR over the 10 year model horizon (costs £52 593 vs £53 943 and QALYs 2.81 vs 2.75), indicating that TAVI dominated SAVR. This appeared to be due to greater postsurgical costs, related to the length and cost of hospital stay. The results appeared robust to a number of deterministic sensitivity and probabilistic analyses. The cost-effectiveness acceptability curve indicated that at the NICE £20 000 willingness to pay threshold per QALY gained, TAVI had a 64.6% likelihood of being cost-effective, compared with 35.4% for SAVR. CONCLUSIONS: TAVI is likely to be a cost-effective treatment for high-risk patients with AS compared with the reference standard of SAVR. However, uncertainty surrounding the long-term outcomes for TAVI patients remains; this could have a substantive impact on estimates of cost-effectiveness.

BACKGROUND: Chemotherapy-induced nausea and vomiting remain difficult symptoms to manage in clinical practice. As standard antiemetic drugs do not fully eliminate these symptoms, it is important to explore the adjuvant role of non-pharmacological and complementary therapies in antiemetic management approaches. Acupressure is one such treatment showing highly suggestive evidence so far of a positive effect, meriting further investigation. OBJECTIVES: the primary objective was to assess the effectiveness and cost-effectiveness of self-acupressure using wristbands compared with sham acupressure wristbands and standard care alone in the management of chemotherapy-induced nausea. Secondary objectives included assessment of the effectiveness and cost-effectiveness of the wristbands in relation to vomiting and quality of life and exploration of any age, gender and emetogenic risk effects. DESIGN: Randomised three-arm sham-controlled trial (Assessment of Nausea in Chemotherapy Research or ANCHoR) with an economic evaluation. Arms include the wristband arm, the sham wristband arm and the standard care only arm. Randomisation consisted of minimisation with a random element balancing for gender, age (16-24, > 24-50, >50 years) and three levels of emetogenic chemotherapy (low, moderate and high). Qualitative interviews were incorporated to shed more light on the quantitative findings. SETTING: Outpatient chemotherapy clinics in three regions in the UK involving 14 different cancer units/centres. PARTICIPANTS: Chemotherapy-naive cancer patients receiving chemotherapy of low, moderate and high emetogenic risk. INTERVENTION: the intervention was acupressure wristbands pressing the P6 point (anterior surface of the forearm). MAIN OUTCOME MEASURES: the Rhodes Index for Nausea/Vomiting, the Multinational Association of Supportive Care in Cancer (MASCC) Antiemesis Tool and the Functional Assessment of Cancer Therapy - General (FACT-G). At baseline participants completed measures of anxiety/depression, nausea/vomiting expectation and expectations from using the wristbands. RESULTS: in total, 500 patients were randomised in the study arms (166 standard care, 166 sham acupressure and 168 acupressure) and data were available for 361 participants for the primary outcome. The primary outcome analysis (nausea in cycle 1) revealed no statistically significant differences between the three arms, although the median nausea experience in patients using wristbands (both real and sham ones) was somewhat lower than that in the antiemetics only group (median nausea experience scores for the four cycles: standard care arm 1.43, 1.71, 1.14, 1.14; sham acupressure arm 0.57, 0.71, 0.71, 0.43; acupressure arm 1.00, 0.93, 0.43, 0). A gender effect was evident (p= 0.002), with women responding more favourably to the use of sham acupressure wristbands than men (odds ratio 0.35 for men and 2.02 for women in the sham acupressure group; 1.27 for men and 1.17 for women in the acupressure group). This suggests a placebo effect. No significant differences were detected in relation to vomiting outcomes, anxiety and quality of life. Some transient adverse effects were reported, including tightness in the area of the wristbands, feeling uncomfortable when wearing them and minor swelling in the wristband area (n= 6).There were no statistically significant cost differences associated with the use of real acupressure bands (£70.66 for the acupressure group, £111.13 for the standard care group and £161.92 for the sham acupressure group). In total, 26 subjects took part in qualitative interviews. The qualitative data suggested that participants perceived the wristbands (both real and sham) as effective and helpful in managing their nausea during chemotherapy. CONCLUSIONS: There were no statistically significant differences between the three arms in terms of nausea, vomiting and quality of life, although apparent resource use was less in both the real acupressure arm and the sham acupressure arm compared with standard care only; therefore; no clear conclusions can be drawn about the use of acupressure wristbands in the management of chemotherapy-related nausea and vomiting. However, the study provided encouraging evidence in relation to an improved nausea experience and some indications of possible cost savings to warrant further consideration of acupressure both in practice and in further clinical trials. TRIAL REGISTRATION: ISRCTN87604299. SOURCE OF FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 17, No. 26. See the HTA programme website for further project information.

BACKGROUND: According to the UK Adult Dental Health Survey (2009) 15% of adults aged 65-74, 30% aged 75-84 and 47% aged >85 years are edentulous and require complete dentures. Patients' quality of life and nutrition status are affected by poor dentures. The quality of the dental impression is the most important issue for improving the fit and comfort of new dentures. There is paucity of RCT evidence for which impression material is best for complete dentures construction. This study aims to compare two impression materials for effectiveness and cost effectiveness. METHODS/DESIGN: IMPROVDENT is a double-blind crossover trial comparing the use of alginate and silicone, two commonly used denture impression materials, in terms of patient preference and cost-effectiveness. Eighty five edentulous patients will be recruited and provided with two sets of dentures, similar in all aspects except for the impression material used (alginate or silicone). Patients will try both sets of dentures for a two-week period, unadjusted, to become accustomed to the feel of the new dentures (habituation period). Patients will then wear each set of dentures for a period of 8 weeks (in random order) during which time the dentures will be adjusted for optimum comfort. Finally, patients will be given both sets of dentures for a further two weeks to wear whichever denture they prefer (confirmation period).Patients will be asked about quality of life and to rate dentures on function and comfort at the end of each trial period and asked which set they prefer at the end of the habituation period (unadjusted denture preference) and confirmation period (adjusted denture preference). A health economic evaluation will estimate incremental cost-effectiveness ratios of producing dentures from the two materials. A qualitative study will investigate the impact of dentures on behaviour and quality of life. FUNDING: IMPROVDENT is funded by NIHR RfPB (PB-PG-0408-16300). DISCUSSION: This trial aims to provide evidence on the costs and quality of dentures cast from two different commonly used impression materials; the intention is to significantly impact on the quality of denture production within NHS dentistry. TRIAL REGISTRATION: ISRCTN Register: ISRCTN01528038 UKCRN Portfolio ID: 8305.

AIMS: Paediatric guidance on diagnosis and treatment of urinary tract infections (UTIs) has in the past largely focused on identifying children with vesicoureteral reflux, thought to be at greatest risk of renal scarring. This practice has been questioned, specifically the accepted association between UTI and end-stage renal failure (ESRF) through renal scarring. The aim of this article is to ascertain whether we can predict with confidence the true level of risk that a child with a first-time UTI will subsequently develop ESRF attributable to UTI. METHODS: Using data available from renal registries, an analytical approach based on previous estimates of risk is used to demonstrate the range of plausible estimates of risk that can be generated and levels of uncertainty that surrounds those estimates. RESULTS: Estimates of the perceived risk of developing ESRF following UTI range from 1/154 to 1/199,900 and are heavily dependent on the assumptions made and the source of data. CONCLUSION: There is considerable uncertainty in the relationship between childhood UTI and risk of ESRF based on the data currently available. Until further evidence is available, clinicians will continue to debate the risk of UTI and ESRF and consensus opinion will continue to guide management.

BACKGROUND: Crohn's disease (CD) is a severe, lifelong disease characterised by inflammation of the gastrointestinal mucosa. The impact on patients and society is high as ill health can be lifelong and can negatively affect patients' quality of life. Costs to the NHS are high, particularly for patients needing hospitalisation. Conventional treatment pathways are complex. More recently, a group of drugs called tumour necrosis factor (TNF) inhibitors (anti-TNF-α agents) have been evaluated for their effectiveness in CD. One of these, infliximab, is currently recommended by the National Institute for Health and Clinical Excellence (NICE; 2002) for patients with severe, active CD where patients are refractory to or intolerant of conventional treatment. OBJECTIVES: to investigate whether there is evidence for greater clinical effectiveness or cost-effectiveness for either adalimumab or infliximab. DATA SOURCES: Cochrane Library (Cochrane Central Register of Controlled Trials) 2007 Issue 2; MEDLINE (Ovid) 2000 to May/June 2007; MEDLINE In-Process & Other Non-Indexed Citations (Ovid) 4 June and 26 June 2007; EMBASE (Ovid) 2000 to May/June 2007. The European Medicines Agency, the US Food and Drug Administration and other relevant websites. REVIEW METHODS: Standard systematic review methods were used for study identification and selection, data extraction and quality assessment. Only randomised controlled trials (RCTs) comparing adalimumab or infliximab with standard treatment (placebo), RCTs comparing adalimumab with infliximab, or RCTs comparing different dosing regimens of either adalimumab or infliximab in adults and children with moderate-to-severe active CD intolerant or resistant to conventional treatment were eligible for inclusion. A systematic review of published studies on the cost and cost-effectiveness of adalimumab and infliximab was undertaken. The economic models of cost-effectiveness submitted by the manufacturers of both drugs were critically appraised and, where appropriate, rerun using parameter inputs based on the evidence identified by the authors of the technology asessment report. A de novo Markov state transition model was constructed to calculate the incremental cost-effectiveness ratio for adalimumab and infliximab therapy compared with standard care. RESULTS: Based on 11 trials, there was evidence from both induction and maintenance trials that both adalimumab and infliximab therapy were beneficial compared with placebo (standard care) for adults with moderate-to-severe CD and, for infliximab, for adults with fistulising CD; results were statistically significant for some time points. Between 6% and 24% (adalimumab), and 21% and 44% (infliximab) more patients achieved remission with anti-TNF-α antibodies than with placebo in the induction trials. Between 24% and 29% (adalimumab), and 14% and 24% (infliximab) more patients achieved remission with anti-TNF-α antibodies in the two large maintenance trials at reported follow-up. In fistulising CD, between 29% and 42% (induction trial) and 23% (maintenance trial) more patients achieved a > 50% reduction in fistulas with infliximab than with placebo at reported follow-up. There was no direct evidence to show that 'responders' were more likely to benefit from treatment than 'non-responders' in the longer term. Few differences were found between treatment and standard care arms for selected adverse events, though high proportions of scheduled crossovers resulted in a lack of a true placebo group in most of the maintenance trials. No published studies on the cost-effectiveness of adalimumab were identified. The four independently funded studies identified for infliximab suggested high cost-effectiveness ratios [all above £50,000/quality-adjusted life-year (QALY) for non-fistulising disease and all above £100,000/QALY for fistulising disease]. A budget impact assessment suggested that total cost to the NHS in England and Wales for induction in severe disease only could range between £17M and £92M and for maintenance for 1 year between £140M and £200M. LIMITATIONS: Regarding clinical effectiveness, there were concerns about the trial design and lack of clarity, which may have affected interpretation of results. None of the trials matched exactly the licence indications or NICE guidance, which specify the use of these drugs in patients with 'severe' disease. All trials were multicentre, and applicability to UK populations, particularly in terms of standard care being provided and in terms of patients having failed or having become intolerant to conventional treatment, was uncertain. The published economic models relied heavily on little information and data from small samples. CONCLUSIONS: Anti-TNF therapy with adalimumab or infliximab may have a beneficial effect compared with standard care on outcome measures for induction and maintenance. The findings were that for induction, both adalimumab and infliximab are cost-effective (dominant relative to standard care) in the management of severe CD, and adalimumab (but not infliximab) is cost-effective for moderate CD, according to limits generally accepted by NICE. On the basis of the analysis presented here, neither drug is likely to be cost-effective as maintenance therapy for moderate or severe disease. Perhaps, most importantly, the analysis reflected the fact that a substantial number of patients would achieve remission under standard care and that the incidence of relapse among those in remission was such that maintenance therapy would have to show greater effectiveness than at present and/or be much less costly than it currently is in order to reach the levels of generally accepted cost-effectiveness. Any future trials need to be designed to meet the particular challenges of measuring and quantifying benefit in this patient group. FUNDING: the research was funded by the HTA programme on behalf of NICE.

BACKGROUND: Trastuzumab has significantly improved survival outcomes for women with Human Epidermal growth factor Receptor 2 (HER2)-positive early breast cancer. Trastuzumab was established as a cost-effective adjuvant treatment in 2006. We present an updated cost-effectiveness analysis from the UK perspective, which explores assumptions about the duration of benefit from treatment, pattern of metastatic recurrence and long-term cardiac toxicity. OBJECTIVE: the objective of this study was to calculate, from the UK NHS perspective, expected costs (year 2008 values) and benefits over the lifetime of an average cohort of women with HER2-positive early breast cancer treated with or without 1 year of adjuvant trastuzumab sequentially after chemotherapy. METHODS: a cost-utility analysis was performed using a discrete-state time-dependent semi-Markov model. Probabilistic sensitivity analysis was used to characterize uncertainty around expected outcomes. Value-of-information (VOI) analysis was used to identify areas of priority for further research. RESULTS: the cost-effectiveness estimates were highly sensitive to the estimated duration of treatment benefit. Trastuzumab remained a cost-effective treatment strategy at a willingness-to-pay threshold of £30,000 per QALY provided the duration of benefit was more than 3.6 years from treatment initiation, assuming the hazard ratio for disease-free survival was 0.63. An increasing proportion of brain metastases with trastuzumab produced a small change towards worse cost effectiveness. Long-term cardiac toxicity needed to rise to high levels to affect overall life expectancy and cost effectiveness. VOI analysis placed highest value on research into the duration of treatment benefit. The relationships between progression-free survival and overall survival and the costs of cancer recurrence were also important. CONCLUSION: the cost effectiveness of adjuvant trastuzumab remains uncertain and dependent on assumptions regarding its clinical effect. Uncertainty around cost effectiveness could be reduced by further research into the duration of treatment effect, particularly in subgroups where this may be shorter. Long-term follow-up is warranted and methods to accurately measure duration of treatment effect and late toxicities should be developed for future adjuvant drug studies.

The purpose of this paper is to provide information about cost-effectiveness analysis and the roles of clinical pharmacologists generally in providing efficient health care. The paper highlights the potential consequences of 'off-label prescribing' and 'indication creep' behaviour given slower growth (or potential cuts) in the NHS budget. This paper highlights the key roles of clinical pharmacologists in delivering an efficient health care system when resources are allocated using cost-effectiveness analyses. It describes what cost-effectiveness analysis (CEA) is and how incremental cost-effectiveness ratios (ICERs) are used to identify efficient options. After outlining the theoretical framework within which using CEA can promote the efficient allocation of the health care budget, it considers the place of disinvestment within achieving efficient resource allocation. Clinical pharmacologists are argued to be critical to providing improved population health under CEA-based resource allocation processes because of their roles in implementation and disinvestment. Given that the challenges facing the United Kingdom National Health Service (NHS) are likely to increase, this paper sets out the stark choices facing clinical pharmacologists.

This article contributes to the literature on older workers and employment, providing a regional perspective on the relationship between age and work. The study is based on interviews in conjunction with occupational-event calendars with 56 individuals in North West England. The primary aim was to gain in-depth understanding of perceived constraints that older people feel hinder their employment prospects within the context of their daily lives. Significant constraints on employment and re-employment were identified and attributed to health, negative perceptions of self, lack of formal human capital and undervaluation of experience, financial disincentives for employers to employ older workers and prevailing ageist attitudes. © the Author(s) 2010.

This is a summary of the evidence review group (ERG) report on the clinical effectiveness and cost-effectiveness of adjuvant imatinib post resection of KIT-positive gastrointestinal stromal tumours (GISTs) compared with resection only in patients at significant risk of relapse. The ERG report is based on the manufacturer's submission to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal (STA) process. The bulk of the clinical evidence submitted was in the form of one randomised controlled trial (RCT), the Z9001 trial, funded by the manufacturer, which compared resection + adjuvant imatinib for 1 year to resection only. Results were immature, with median recurrence-free survival (RFS) not yet having been reached at the time of analysis. The trial did provide evidence of a delay in disease recurrence [1-year RFS rate of 98% in the imatinib arm vs 83% in the placebo arm [hazard ratio (HR) 0.35, 95% confidence interval (CI) 0.22 to 0.53, p < 0.0001)] but no evidence of an overall survival benefit. There was no long-term evidence around the rate of imatinib resistance over time with different treatment strategies (± adjuvant treatment). The relevant patient group for this appraisal is those at significant risk of relapse. These form a subgroup of the Z9001 trial, and all information regarding this group was designated 'Commercial-in-Confidence' (CIC). Median observation time for RFS was also CIC. The manufacturer constructed a Markov model comprising 10 health states designed to estimate costs and effects of treatment over a lifetime time horizon. The manufacturer's estimate of the base-case incremental cost-effectiveness ratio (ICER) was 22,937 pounds/quality-adjusted life-year (subsequently amended by the manufacturer to 23,601 pounds). While the structure of the model reasonably reflected the natural history of the disease, the ERG had numerous concerns regarding the selection of, and assumptions around, input parameters (utilities, monthly probabilities of recurrence and death). Furthermore, the model was set up in such a way that any delay in recurrence translated directly into a survival benefit, an assumption that has no evidence base. A further assumption not supported by evidence was that any treatment benefit gained in the first year is carried on for a further 2 years at the same rate. Appropriate probabilistic sensitivity analysis was undertaken on the base case only, but not on scenario analyses, or choice of model used to estimate long-term survival data. The model was not amenable to changes in input values, thus limiting any additional analyses by the ERG to test assumptions. Due to the large number of uncertainties and assumptions, the estimated ICERs should be regarded as highly uncertain. The guidance issued by NICE in June 2010 as a result of the STA does not recommend imatinib as adjuvant treatment after resection of gastrointestinal stromal tumours, although individuals currently receiving adjuvant imatinib should have the option to continue treatment until they and their clinician consider it appropriate to stop.

OBJECTIVE: to review non-drug treatments for dementia; to provide a source of evidence for informal carers who want ideas about non-drug approaches for dementia, that they might try or that they could try to access. The systematic review addresses: what non-drug treatments work and what do they work for? What non-drug treatments might work and what for? What non-drug treatments do not work? METHODS: Literature searches of seven electronic databases (AMED, CINAHL, EMBASE, MEDLINE, PSYCINFO, Cochrane Library of Systematic Reviews and DARE) were carried out in November 2007 using the following search terms (or derivatives): dementia/Alzheimer's AND Review AND non-drug therapies and aimed at finding systematic reviews. RESULTS: Thirty-three reviews were identified; 25 were judged to be high or good quality. Studies within these systematic reviews were characterised by weak study designs with small sample numbers. Three interventions were found to be effective for use with particular symptoms of dementia: music or music therapy, hand massage or gentle touch and physical activity/exercise. CONCLUSIONS: Whilst informal carers can apply some of the interventions highlighted in the home setting at little or no cost to themselves or to health or social care services, others are likely to require training or instruction. Service providers and commissioners should explore current and future provision of more structured group activities for people with dementia; in particular the provision of group music therapy and group exercise activities that meet the needs of both the person with dementia and their carer.

The impact of informal care responsibilities on the willingness and ability of caregivers to undertake paid employment has been the subject of a number of studies. In contrast, the effect of employment status on willingness to undertake informal care has been less well explored. This paper concentrates on this less-studied direction of causality using the data provided by 15 waves of the British Household Panel Survey. We find that employment participation and earnings both impact negatively on willingness to supply informal care. This evidence has implications for health and social care policy since informal care has been shown to be a significant substitute for formal long-term care.

This paper reports on interviews with 30 carers of working age in North West England. Respondents revealed a general dissatisfaction with government initiatives and policy. The findings suggest that in the main either the policy, its implementation at grassroots level, or both have had little impact. ©PTM Publishers Limited.

© 2008, MA Healthcare Ltd. All rights reserved. Aims: the worldwide phenomenon of an ageing population has considerable consequences for health and health care; leading to greater demand for long-term care and support from families for older relatives. In the UK this, together with the preference for dependent older people to be cared for in the community, has led to the growth of intermediate care services (ICS) that bridge hospital and home offering rehabilitation and care. However, there has been limited in-depth exploration of carer perspectives of these services. This study therefore aimed to explore the impact of ICS on informal carers.Methods: an overview of UK Government policy on carers is provided to set the context. Qualitative semi-structured interviews, which explored participants’ lives as carers, their daily routine and what caring meant to them, were conducted with 19 informal carers within one ICS in north-west England.Findings: the ICS was not viewed in isolation; the impact of the ICS on the carer depended on previous experience and quality of health care, involvement in the decision making process, expectations and communication.Conclusions: a whole systems approach should be encouraged to increase awareness of carers’ experiences and the lasting impact negative experiences can have.

In the United Kingdom, informal carers look after relatives or friends who need extra support because of age, physical or learning disability, or illness. The burden of informal care work falls on women, who often care for longer hours and durations than men. This paper considers the impact that caring responsibilities have on women's employment. The research is based on a dedicated questionnaire and in-depth interviews with informal caregivers. The results suggest that carers' employment is affected by the duration of a caring episode, financial considerations, the needs of the person they care for, carers' beliefs about the compatibility of informal care and paid work, and employers' willingness to accommodate carers' needs. Overall, the research confirms that informal carers continue to face difficulties when they try to combine employment and care in spite of recent policy initiatives designed to help them. © 2008 IAFFE.

This paper aims to report a synopsis of a recent systematic review of the literature regarding the effectiveness of workplace physical activity interventions, commissioned by the National Institute for Health and Clinical Excellence (NICE). A search for English-language papers published between 1996 and 2007 was conducted using 12 relevant databases and associated grey literature. Search protocols and analysis regarding study quality as recommended by NICE were utilised. Key inclusion criteria were, workplace intervention aiming to increase physical activity, intervention aimed at working adults, intervention initiated/endorsed by the employer, physical activity outcome. Thirty-three studies (38 papers) met the inclusion criteria and were independently reviewed (checked by two reviewers) with a narrative synthesis of findings. Fourteen studies were graded as high quality or good quality. Evidence from previous systematic reviews was inconclusive. Data regarding the effectiveness of stair walking interventions was limited and intervention effects were short-lived. Three public sector studies provided evidence that workplace walking interventions using pedometers can increase daily step counts. One good quality study reported a positive intervention effect on walking to work behaviour (active travel) in economically advantaged female employees. There was strong evidence that workplace counselling influenced physical activity behaviour. There is a dearth of evidence for small and medium enterprises. Due to the necessary UK focus and time constraints, only studies from Europe, Australia, New Zealand and Canada were included. The paper shows that there is a growing evidence base that workplace physical activity interventions can positively influence physical activity behaviour. © 2008, Emerald Group Publishing Limited

OBJECTIVES: to explore library staff and health professionals' views on the effectiveness of information skills training and librarian mediated searching as methods of providing information for patient care. This is the second article describing the Effective Methods of Providing InfoRmation for patIent Care (EMPIRIC) project. The first paper, in a previous issue of this journal (Brettle et al. The costs and effectiveness of information skills training and mediated searching: quantitative results for the EMPIRIC project. Health Information and Libraries Journal 2006, 23, 239-247) describes the quantitative results. METHODS: a questionnaire survey to library staff and health professionals in the North West. Data was collected on perceptions of services, satisfaction and service usage. Statistical data were analysed using the Statistical Package for the Social Sciences (SPSS) and qualitative data using thematic analysis. RESULTS: Both information skills training and mediated searches are perceived by library staff and health professionals to be effective. There is strong support for mediated searches carried out on behalf of the health professional and information skills training to enable them to carry out their own searches. The results provide insights into the effectiveness of the services and the factors that make them effective. CONCLUSIONS: Evidence and stakeholders views support the provision of both information skills training and mediated search services. Both services are valued by users who see them as complementary methods of obtaining information depending on their needs at different times.

The process by which residents are admitted to a therapeutic community is significant in enabling a sense of connection in the community; the involvement of peers (current community residents) is one strategy by which to achieve this with the potential for benefits to new arrivals, current residents and the community as a whole (Norton 1999). This paper reports on a study that explored the value added by including residents in the admissions day process of Webb House Democratic Therapeutic Community. Focus groups elicited the perceptions of the key groups involved, the management, residents and rota staff. The study found engagement of new residents was hampered by a task-orientated structure. Conversely, lack of structure and clear delineation of staff, residents and their roles meant both new and current residents felt uncomfortable. Whilst those managing the service believed involvement of residents to be worthwhile and constructive, staff held mixed views. Conflict between residents and new arrivals arose as a result of the perceived special treatment received by the new arrivals which could lead to alienation from their peers. Residents had an empathy with new arrivals but felt involvement in the process to be a chore. © the Author(s).

OBJECTIVES: to compare the effectiveness and costs of providing information for patient care via librarian-mediated searches and information-skills training. METHODS: a questionnaire survey to library staff and health professionals in the North West. Data was collected on perceptions of services, satisfaction and service usage, allowing a cost analysis to be undertaken. Statistical data was analysed using Statistical Package for the Social Sciences (spss). RESULTS: Using satisfaction and use of skills as outcome measures, both mediated searches and information skills training are effective. A breakdown of costs per type of training session and literature search is provided. Cost-effectiveness is dependent on whether costs are viewed from a library or trust point of view. Providing information skills training does not reduce the volume of mediated-search requests. CONCLUSIONS: No one method of providing information for health professionals is more effective or cost-effective than another. A decision about which services to provide cannot be made on the basis of effectiveness or costs alone; the views of library staff and the health professionals they serve should also be taken into account. A proactive approach and targeting training towards those who are most likely to benefit may be an appropriate way forward.

INTRODUCTION: Economic evaluation, linking the costs and consequences of an intervention to indicate the potential benefits of alternative interventions, is becoming established as one of the core tools for decision making in health care. As knowledge of the safety and effectiveness of complementary and alternative medicine (CAM) interventions increases, economic evaluation within CAM has a heightened significance. OBJECTIVE: to explore whether the present framework for economic evaluation fits CAM and what modifications if any are needed for its application. DESIGN: Systematic review. METHODS: a comprehensive search of four databases was undertaken (NHS Economic Evaluation Database, AMED, MEDLINE, CINAHL). Studies were included if they took the form of a comparative analysis of costs and consequences of a CAM treatment and were written in English. Each study was reviewed using a set of methodological questions to judge their quality as economic evaluations. RESULTS: a total of 19 studies were identified, of which 9 were cost-effectiveness studies, 7 cost-consequence studies, 2 cost-minimization studies, and 1 cost-benefit analysis. Seventeen (17) of the studies involved CAM treatments being used alongside mainstream or conventional treatments. The majority of the treatments aimed to alleviate pain, including chronic pain, back pain, neck pain, and migraine. Only a small minority of studies addressed wider outcomes of particular relevance to CAM disciplines. Nine (9) adopted a service provider perspective only, 7 included wider sickness absence costs and 3 patient costs. Only 1 study included costs to relatives. The quality of the cost and benefit dimensions of the studies was mixed. CONCLUSIONS: a CAM sensitive approach to economic evaluation is required. This needs to include a focus on outcomes that explore the range of effects of CAM treatment, an exploration of the client's perspective and not just that of the service provider and study designs that facilitate the individualized practitioner approach so central to CAM treatment.

BACKGROUND: Nurses have always looked to support their activities through the presence of unregistered co-workers. In the later part of the 20th century this workforce has evolved from a predominance of students to increasing use of variously prepared second level nurses, nursing assistants and Health Care Support Workers. METHOD: the study evaluated the development of 'advanced' support workers for intensive care settings, examining the views of the multi-disciplinary team, the support workers, and making observations of the work undertaken. Ethical approval was gained via a multi-centre committee. Individual interviews, focus groups and fieldwork provided rich qualitative data. It is this, and the views of support workers themselves on which we focus in this report. RESULTS: Senior support workers have a potentially important, but as yet insufficiently clear role to play. Key tasks such as taking arterial blood gas symbolise their rite of passage into the role. Expectations vary by locality and by person and there is great concern over accountability for work done. Delegation of work depends as much on experience as training and individuals are reluctant to delegate to staff they have not personally assessed and come to know as 'competent'. CONCLUSION: These workers should have clear and adequately remunerated career pathways open to them, in particular into nursing and allied health disciplines, and should probably be licensed to practice.

This article identifies that the introduction of the support worker role in the critical care team facilitates flexibility when organizing and managing patient care. Qualified nurses' time can be used more effectively, enhancing the quality of the patient care delivered. Aspects of the qualified nurses' workload in critical care can be shared and delegated successfully to unqualified staff. It is our view that staffing levels in critical care environments need to be reviewed with more flexible working practices to meet the current and future demands of critical care. There is a need for national consensus amongst qualified nurses to clarify and define the role of the support worker and develop a critical care competency framework to standardize training. To ensure proficiency, adequate training and appropriate accountability, support workers require regulation by a nationally recognized body.