Performance of the EQ-5D-5L Plus Respiratory Bolt-On in the Birmingham Chronic Obstructive Pulmonary Disease Cohort Study.

OBJECTIVES: A respiratory bolt-on dimension for the EQ-5D-5L has recently been developed and valued by the general public. This study aimed to validate the EQ-5D-5L plus respiratory dimension (EQ-5D-5L+R) in a large group of patients with chronic obstructive pulmonary disease (COPD). METHODS: Validation was undertaken with data from the Birmingham COPD Cohort Study, a longitudinal UK study of COPD primary care patients. Data on the EQ-5D-5L+R were collected from 1008 responding participants during a follow-up questionnaire in 2017 and combined with (previously collected) data on patient and disease characteristics. Descriptive and correlation analyses were performed on the EQ-5D-5L+R dimensions and utilities, in relation to COPD characteristics and compared with the EQ-5D-5L without respiratory dimension. Multivariate regression models were estimated to test whether regression coefficients of clinical characteristics differed between the EQ-5D-5L+R utility and the EQ-5D-5L utility. RESULTS: Correlation coefficients for the EQ-5D-5L+R utility with COPD parameters were slightly higher than the EQ-5D-5L utility. Both instruments displayed discriminant validity but analyses in clinical subgroups of patients showed larger absolute differences in utilities for the EQ-5D-5L+R. In the multivariate analyses, only the coefficient for the COPD Assessment Test score was higher for the model using the EQ-5D-5L+R utility as outcome. CONCLUSIONS: This study showed that the addition of a respiratory domain to the EQ-5D-5L led to small improvements in the instrument's performance. Comparability of the EQ-5D across diseases, currently considered one of its strengths, would have to be traded off against a modest improvement in utility difference when adding the respiratory dimension.

To Trial or Not to Trial Before Spinal Cord Stimulation for Chronic Neuropathic Pain: The Patients' View From the TRIAL-STIM Randomized Controlled Trial.

Objectives Spinal cord stimulation (SCS) is an established treatment of chronic neuropathic pain. Although a temporary SCS screening trial is widely used to determine suitability for a permanent implant, its evidence base is limited. The recent TRIAL-STIM study (a randomized controlled trial at three centers in the United Kingdom) found no evidence that an SCS screening trial strategy provides superior patient outcomes as compared with a no trial approach. As part of the TRIAL-STIM study, we undertook a nested qualitative study to ascertain patients' preferences in relation to undergoing a screening trial or not. Materials and Methods We interviewed 31 patients sampled from all three centers and both study arms (screening trial/no trial) prior to SCS implantation, and 23 of these patients again following implantation (eight patients were lost to follow-up). Interviews were undertaken by telephone and audio-recorded, then transcripts were subject to thematic analysis. In addition, participants were asked to state their overall preference for a one-stage (no screening trial) versus two-stage (screening trial) implant procedure on a five-point Likert scale, before and after implantation. Results Emergent themes favoured the option for a one-stage SCS procedure. Themes identified include: saving time (off work, in hospital, attending appointments), avoiding the worry about having "loose wires" in the two-stage procedure, having only one period of recovery, and saving NHS resources. Participants' rated preferences show similar support for a one-stage procedure without a screening trial. Conclusions Our findings indicate an overwhelming preference among participants for a one-stage SCS procedure both before and after the implant, regardless of which procedure they had undergone. The qualitative study findings further support the TRIAL-STIM RCT results.

Does a screening trial for spinal cord stimulation in patients with chronic pain of neuropathic origin have clinical utility and cost-effectiveness (TRIAL-STIM)? A randomised controlled trial.

Spinal cord stimulation (SCS) is an established treatment of chronic neuropathic pain. Although a temporary SCS screening trial is widely used to determine whether a patient should receive permanent SCS implant, its evidence base is limited. We aimed to establish the clinical utility, diagnostic accuracy, and cost-effectiveness of an SCS screening trial. A multicentre single-blind, parallel two-group randomised controlled superiority trial was undertaken at 3 centres in the United Kingdom. Patients were randomised 1:1 to either SCS screening trial strategy (TG) or no trial screening strategy (NTG). Treatment was open label, but outcome assessors were masked. The primary outcome measure was numerical rating scale (NRS) pain at 6-month follow-up. Between June 2017 and September 2018, 105 participants were enrolled and randomised (TG = 54, NTG = 51). Mean numerical rating scale pain decreased from 7.47 at baseline (before SCS implantation) to 4.28 at 6 months in TG and from 7.54 to 4.49 in NTG (mean group difference: 0.2, 95% confidence interval [CI]: -1.2 to 0.9, P = 0.89). We found no difference between TG and NTG in the proportion of pain responders or other secondary outcomes. Spinal cord stimulation screening trial had a sensitivity of 100% (95% CI: 78-100) and specificity of 8% (95% CI: 1-25). The mean incremental cost-effectiveness ratio of TG vs NTG was £78,895 per additional quality-adjusted life-year gained. In conclusion, although the SCS screening trial may have some diagnostic utility, there was no evidence that an SCS screening TG provides superior patient outcomes or is cost-effective compared to a no trial screening approach.

Surgical site infection and costs in low- and middle-income countries: A systematic review of the economic burden.

BACKGROUND: Surgical site infection (SSI) is a worldwide problem which has morbidity, mortality and financial consequences. The incidence rate of SSI is high in Low- and Middle-Income countries (LMICs) compared to high income countries, and the costly surgical complication can raise the potential risk of financial catastrophe. OBJECTIVE: The aim of the study is to critically appraise studies on the cost of SSI in a range of LMIC studies and compare these estimates with a reference standard of high income European studies who have explored similar SSI costs. METHODS: A systematic review was undertaken using searches of two electronic databases, EMBASE and MEDLINE In-Process & Other Non-Indexed Citations, up to February 2019. Study characteristics, comparator group, methods and results were extracted by using a standard template. RESULTS: Studies from 15 LMIC and 16 European countries were identified and reviewed in full. The additional cost of SSI range (presented in 2017 international dollars) was similar in the LMIC ($174-$29,610) and European countries ($21-$34,000). Huge study design heterogeneity was encountered across the two settings. DISCUSSION: SSIs were revealed to have a significant cost burden in both LMICs and High Income Countries in Europe. The magnitude of the costs depends on the SSI definition used, severity of SSI, patient population, choice of comparator, hospital setting, and cost items included. Differences in study design affected the comparability across studies. There is need for multicentre studies with standardized data collection methods to capture relevant costs and consequences of the infection across income settings.

Correction to: Does a Screening Trial for Spinal Cord Stimulation in Patients with Chronic Pain of Neuropathic Origin have Clinical Utility and Cost-Effectiveness? (TRIAL-STIM Study): study protocol for a randomised controlled trial.

Following publication of the original article [1], we have been notified that the final specification of randomisation implemented in the study is slightly different to that stated in the protocol and needs to be corrected as follows.

Factors associated with costs and health outcomes in patients with Back and leg pain in primary care: a prospective cohort analysis.

BACKGROUND: There is limited research on the economic burden of low back-related leg pain, including sciatica. The aim of this study was to describe healthcare resource utilisation and factors associated with cost and health outcomes in primary care patients consulting with symptoms of low back-related leg pain including sciatica. METHODS: This study is a prospective cohort of 609 adults visiting their family doctor with low back-related leg pain, with or without sciatica in a United Kingdom (UK) Setting. Participants completed questionnaires, underwent clinical assessments, received an MRI scan, and were followed-up for 12-months. The economic analysis outcome was the quality-adjusted life year (QALY) calculated from the EQ-5D-3 L data obtained at baseline, 4 and 12-months. Costs were measured based on patient self-reported information on resource use due to back-related leg pain and results are presented from a UK National Health Service (NHS) and Societal perspective. Factors associated with costs and outcomes were obtained using a generalised linear model. RESULTS: Base-case results showed improved health outcomes over 12-months for the whole cohort and slightly higher QALYs for patients in the sciatica group. NHS resource use was highest for physiotherapy and GP visits, and work-related productivity loss highest from a societal perspective. The sciatica group was associated with significantly higher work-related productivity costs. Cost was significantly associated with factors such as self-rated general health and care received as part of the study, while quality of life was significantly predicted by self-rated general health, and pain intensity, depression, and disability scores. CONCLUSIONS: Our results contribute to understanding the economics of low back- related leg pain and sciatica and may provide guidance for future actions on cost reduction and health care improvement strategies. TRIAL REGISTRATION: 13/09/2011 Retrospectively registered; ISRCTN62880786 .

Does a Screening Trial for Spinal Cord Stimulation in Patients with Chronic Pain of Neuropathic Origin have Clinical Utility and Cost-Effectiveness? (TRIAL-STIM Study): study protocol for a randomised controlled trial.

BACKGROUND: The TRIAL-STIM Study aims to assess the diagnostic performance, clinical outcomes and cost-effectiveness of a screening trial prior to full implantation of a spinal cord stimulation (SCS) device. METHODS/DESIGN: The TRIAL-STIM Study is a superiority, parallel-group, three-centre, randomised controlled trial in patients with chronic neuropathic pain with a nested qualitative study and economic evaluation. The study will take place in three UK centres: South Tees Hospitals NHS Foundation Trust (The James Cook University Hospital); Basildon and Thurrock University Hospitals NHS Foundation Trust; and Leeds Teaching Hospitals NHS Trust. A total of 100 adults undergoing SCS implantation for the treatment of neuropathy will be included. Subjects will be recruited from the outpatient clinics of the three participating sites and randomised to undergo a screening trial prior to SCS implant or an implantation-only strategy in a 1:1 ratio. Allocation will be stratified by centre and minimised on patient age (≥ 65 or < 65 years), gender, presence of failed back surgery syndrome (or not) and use of high frequency (HF10™) (or not). The primary outcome measure is the numerical rating scale (NRS) at 6 months compared between the screening trial and implantation strategy and the implantation-only strategy. Secondary outcome measures will include diagnostic accuracy, the proportion of patients achieving at least 50% and 30% pain relief at 6 months as measured on the NRS, health-related quality-of-life (EQ-5D), function (Oswestry Disability Index), patient satisfaction (Patients' Global Impression of Change) and complication rates. A nested qualitative study will be carried out in parallel for a total of 30 of the patients recruited in each centre (10 at each centre) to explore their views of the screening trial, implantation and overall use of the SCS device. The economic evaluation will take the form of a cost-utility analysis. DISCUSSION: The TRIAL-STIM Study is a randomised controlled trial with a nested qualitative study and economic evaluation aiming to determine the clinical utility of screening trials of SCS as well as their cost-effectiveness. The nested qualitative study will seek to explore the patient's view of the screening trials, implantation and overall use of SCS. TRIAL REGISTRATION: ISRCTN, ISRCTN60778781 . Registered on 15 August 2017.

Understanding and Identifying Key Issues with the Involvement of Clinicians in the Development of Decision-Analytic Model Structures: A Qualitative Study.

INTRODUCTION: Decision-analytic models play an essential role in informing healthcare resource allocation decisions; however, their value to decision makers will depend on model structures being clinically valid to determine cost-effectiveness recommendations. Clinician involvement can help modellers to develop clinically valid but straightforward structures; however, there is little guidance available on methods for clinician input to model structure. This study aims to provide an in-depth exploration of clinician involvement in structural development, highlighting key issues and generating recommendations to optimise practices. METHODS: A qualitative study was undertaken with a range of modellers and clinicians working in different modelling contexts. In-depth interviews and case studies using observations were carried out to understand how clinicians are involved in model structural development and to identify problems and optimal approaches from informants' perspectives. RESULTS: Twenty-four interviews and two case studies were undertaken with modellers and modelling teams. Key issues included the number and diversity of clinicians contributing to structural development, potentially impacting the generalisability of structures, and problems with clinician understanding of important information to contribute to model pathways. Modellers and clinicians suggested that clinician training in modelling could enhance structural processes. CONCLUSIONS: Recommendations to optimise current practices include recruiting clinicians from a variety of backgrounds and using discussions between experts to develop valid and generalisable structures. Future research should focus on developing training materials for clinicians and finding ways to help modellers recruit clinicians from different settings.

Self management of patients with mild COPD in primary care: randomised controlled trial.

OBJECTIVE: To evaluate the effectiveness of telephone health coaching delivered by a nurse to support self management in a primary care population with mild symptoms of chronic obstructive pulmonary disease (COPD). DESIGN: Multicentre randomised controlled trial. SETTING: 71 general practices in four areas of England. PARTICIPANTS: 577 patients with Medical Research Council dyspnoea scale scores of 1 or 2, recruited from primary care COPD registers with spirometry confirmed diagnosis. Patients were randomised to telephone health coaching (n=289) or usual care (n=288). INTERVENTIONS: Telephone health coaching intervention delivered by nurses, underpinned by Social Cognitive Theory. The coaching promoted accessing smoking cessation services, increasing physical activity, medication management, and action planning (4 sessions over 11 weeks; postal information at weeks 16 and 24). The nurses received two days of training. The usual care group received a leaflet about COPD. MAIN OUTCOME MEASURES: The primary outcome was health related quality of life at 12 months using the short version of the St George's Respiratory Questionnaire (SGRQ-C). RESULTS: The intervention was delivered with good fidelity: 86% of scheduled calls were delivered; 75% of patients received all four calls. 92% of patients were followed-up at six months and 89% at 12 months. There was no difference in SGRQ-C total score at 12 months (mean difference -1.3, 95% confidence interval -3.6 to 0.9, P=0.23). Compared with patients in the usual care group, at six months follow-up, the intervention group reported greater physical activity, more had received a care plan (44% v 30%), rescue packs of antibiotics (37% v 29%), and inhaler use technique check (68% v 55%). CONCLUSIONS: A new telephone health coaching intervention to promote behaviour change in primary care patients with mild symptoms of dyspnoea did lead to changes in self management activities, but did not improve health related quality of life. TRIAL REGISTRATION: Current controlled trials ISRCTN 06710391.

Efficacy of self-monitored blood pressure, with or without telemonitoring, for titration of antihypertensive medication (TASMINH4): an unmasked randomised controlled trial.

BACKGROUND: Studies evaluating titration of antihypertensive medication using self-monitoring give contradictory findings and the precise place of telemonitoring over self-monitoring alone is unclear. The TASMINH4 trial aimed to assess the efficacy of self-monitored blood pressure, with or without telemonitoring, for antihypertensive titration in primary care, compared with usual care. METHODS: This study was a parallel randomised controlled trial done in 142 general practices in the UK, and included hypertensive patients older than 35 years, with blood pressure higher than 140/90 mm Hg, who were willing to self-monitor their blood pressure. Patients were randomly assigned (1:1:1) to self-monitoring blood pressure (self-montoring group), to self-monitoring blood pressure with telemonitoring (telemonitoring group), or to usual care (clinic blood pressure; usual care group). Randomisation was by a secure web-based system. Neither participants nor investigators were masked to group assignment. The primary outcome was clinic measured systolic blood pressure at 12 months from randomisation. Primary analysis was of available cases. The trial is registered with ISRCTN, number ISRCTN 83571366. FINDINGS: 1182 participants were randomly assigned to the self-monitoring group (n=395), the telemonitoring group (n=393), or the usual care group (n=394), of whom 1003 (85%) were included in the primary analysis. After 12 months, systolic blood pressure was lower in both intervention groups compared with usual care (self-monitoring, 137·0 [SD 16·7] mm Hg and telemonitoring, 136·0 [16·1] mm Hg vs usual care, 140·4 [16·5]; adjusted mean differences vs usual care: self-monitoring alone, -3·5 mm Hg [95% CI -5·8 to -1·2]; telemonitoring, -4·7 mm Hg [-7·0 to -2·4]). No difference between the self-monitoring and telemonitoring groups was recorded (adjusted mean difference -1·2 mm Hg [95% CI -3·5 to 1·2]). Results were similar in sensitivity analyses including multiple imputation. Adverse events were similar between all three groups. INTERPRETATION: Self-monitoring, with or without telemonitoring, when used by general practitioners to titrate antihypertensive medication in individuals with poorly controlled blood pressure, leads to significantly lower blood pressure than titration guided by clinic readings. With most general practitioners and many patients using self-monitoring, it could become the cornerstone of hypertension management in primary care. FUNDING: National Institute for Health Research via Programme Grant for Applied Health Research (RP-PG-1209-10051), Professorship to RJM (NIHR-RP-R2-12-015), Oxford Collaboration for Leadership in Applied Health Research and Care, and Omron Healthcare UK.

Routine low-dose continuous or nocturnal oxygen for people with acute stroke: three-arm Stroke Oxygen Supplementation RCT.

BACKGROUND: Stroke is a major cause of death and disability worldwide. Hypoxia is common after stroke and is associated with worse outcomes. Oxygen supplementation could prevent hypoxia and secondary brain damage. OBJECTIVES: (1) To assess whether or not routine low-dose oxygen supplementation in patients with acute stroke improves outcome compared with no oxygen; and (2) to assess whether or not oxygen given at night only, when oxygen saturation is most likely to be low, is more effective than continuous supplementation. DESIGN: Multicentre, prospective, randomised, open, blinded-end point trial. SETTING: Secondary care hospitals with acute stroke wards. PARTICIPANTS: Adult stroke patients within 24 hours of hospital admission and 48 hours of stroke onset, without definite indications for or contraindications to oxygen or a life-threatening condition other than stroke. INTERVENTIONS: Allocated by web-based minimised randomisation to: (1) continuous oxygen: oxygen via nasal cannula continuously (day and night) for 72 hours after randomisation at a flow rate of 3 l/minute if baseline oxygen saturation was ≤ 93% or 2 l/minute if > 93%; (2) nocturnal oxygen: oxygen via nasal cannula overnight (21:00-07:00) for three consecutive nights. The flow rate was the same as the continuous oxygen group; and (3) control: no routine oxygen supplementation unless required for reasons other than stroke. MAIN OUTCOME MEASURES: Primary outcome: disability assessed by the modified Rankin Scale (mRS) at 3 months by postal questionnaire (participant aware, assessor blinded). Secondary outcomes at 7 days: neurological improvement, National Institutes of Health Stroke Scale (NIHSS), mortality, and the highest and lowest oxygen saturations within the first 72 hours. Secondary outcomes at 3, 6, and 12 months: mortality, independence, current living arrangements, Barthel Index, quality of life (European Quality of Life-5 Dimensions, three levels) and Nottingham Extended Activities of Daily Living scale by postal questionnaire. RESULTS: In total, 8003 patients were recruited between 24 April 2008 and 17 June 2013 from 136 hospitals in the UK [continuous, n = 2668; nocturnal, n = 2667; control, n = 2668; mean age 72 years (standard deviation 13 years); 4398 (55%) males]. All prognostic factors and baseline characteristics were well matched across the groups. Eighty-two per cent had ischaemic strokes. At baseline the median Glasgow Coma Scale score was 15 (interquartile range 15-15) and the mean and median NIHSS scores were 7 and 5 (range 0-34), respectively. The mean oxygen saturation at randomisation was 96.6% in the continuous and nocturnal oxygen groups and 96.7% in the control group. Primary outcome: oxygen supplementation did not reduce disability in either the continuous or the nocturnal oxygen groups. The unadjusted odds ratio for a better outcome (lower mRS) was 0.97 [95% confidence interval (CI) 0.89 to 1.05; p = 0.5] for the combined oxygen groups (both continuous and nocturnal together) (n = 5152) versus the control (n = 2567) and 1.03 (95% CI 0.93 to 1.13; p = 0.6) for continuous versus nocturnal oxygen. Secondary outcomes: oxygen supplementation significantly increased oxygen saturation, but did not affect any of the other secondary outcomes. LIMITATIONS: Severely hypoxic patients were not included. CONCLUSIONS: Routine low-dose oxygen supplementation in stroke patients who are not severely hypoxic is safe, but does not improve outcome after stroke. FUTURE WORK: To investigate the causes of hypoxia and develop methods of prevention. TRIAL REGISTRATION: Current Controlled Trials ISRCTN52416964 and European Union Drug Regulating Authorities Clinical Trials (EudraCT) number 2006-003479-11. FUNDING DETAILS: This project was funded by the National Institute for Health Research (NIHR) Research for Patient Benefit and Health Technology Assessment programmes and will be published in full in Health Technology Assessment; Vol. 22, No. 14. See the NIHR Journals Library website for further project information.

How Qualitative Methods Can be Used to Inform Model Development.

Decision-analytic models play a key role in informing healthcare resource allocation decisions. However, there are ongoing concerns with the credibility of models. Modelling methods guidance can encourage good practice within model development, but its value is dependent on its ability to address the areas that modellers find most challenging. Further, it is important that modelling methods and related guidance are continually updated in light of any new approaches that could potentially enhance model credibility. The objective of this article was to highlight the ways in which qualitative methods have been used and recommended to inform decision-analytic model development and enhance modelling practices. With reference to the literature, the article discusses two key ways in which qualitative methods can be, and have been, applied. The first approach involves using qualitative methods to understand and inform general and future processes of model development, and the second, using qualitative techniques to directly inform the development of individual models. The literature suggests that qualitative methods can improve the validity and credibility of modelling processes by providing a means to understand existing modelling approaches that identifies where problems are occurring and further guidance is needed. It can also be applied within model development to facilitate the input of experts to structural development. We recommend that current and future model development would benefit from the greater integration of qualitative methods, specifically by studying 'real' modelling processes, and by developing recommendations around how qualitative methods can be adopted within everyday modelling practice.

Telemonitoring and/or self-monitoring of blood pressure in hypertension (TASMINH4): protocol for a randomised controlled trial.

BACKGROUND: Self-monitoring of hypertension is associated with lower systolic blood pressure (SBP). However, evidence for the use of self-monitoring to titrate antihypertensive medication by physicians is equivocal. Furthermore, there is some evidence for the efficacy of telemonitoring in the management of hypertension but it is not clear what this adds over and above self-monitoring. This trial aims to evaluate whether GP led antihypertensive titration using self-monitoring results in lower SBP compared to usual care and whether telemonitoring adds anything to self-monitoring alone. METHODS/DESIGN: This will be a pragmatic primary care based, unblinded, randomised controlled trial of self-monitoring of BP with or without telemonitoring compared to usual care. Eligible patients will have poorly controlled hypertension (>140/90 mmHg) and will be recruited from primary care. Participants will be individually randomised to either usual care, self-monitoring alone, or self-monitoring with telemonitoring. The primary outcome of the trial will be difference in clinic SBP between intervention and control groups at 12 months adjusted for baseline SBP, gender, BP target and practice. At least 1110 patients will be sufficient to detect a difference in SBP between self-monitoring with or without telemonitoring and usual care of 5 mmHg with 90% power with an adjusted alpha of 0.017 (2-sided) to adjust for all three pairwise comparisons. Other outcomes will include adherence of anti-hypertensive medication, lifestyle behaviours, health-related quality of life, and adverse events. An economic analysis will consider both within trial costs and a model extrapolating the results thereafter. A qualitative sub study will gain insights into the views, experiences and decision making processes of patients and health care professionals focusing on the acceptability of self-monitoring and telemonitoring in the routine management of hypertension. DISCUSSION: The results of the trial will be directly applicable to primary care in the UK. If successful, self-monitoring of BP in people with hypertension would be applicable to hundreds of thousands of individuals in the UK. TRIAL REGISTRATION: ISRCTN 83571366 . Registered 17 July 2014.

The prognostic utility of tests of platelet function for the detection of 'aspirin resistance' in patients with established cardiovascular or cerebrovascular disease: a systematic review and economic evaluation.

BACKGROUND: The use of aspirin is well established for secondary prevention of cardiovascular disease. However, a proportion of patients suffer repeat cardiovascular events despite being prescribed aspirin treatment. It is uncertain whether or not this is due to an inherent inability of aspirin to sufficiently modify platelet activity. This report aims to investigate whether or not insufficient platelet function inhibition by aspirin ('aspirin resistance'), as defined using platelet function tests (PFTs), is linked to the occurrence of adverse clinical outcomes, and further, whether or not patients at risk of future adverse clinical events can be identified through PFTs. OBJECTIVES: To review systematically the clinical effectiveness and cost-effectiveness evidence regarding the association between PFT designation of 'aspirin resistance' and the risk of adverse clinical outcome(s) in patients prescribed aspirin therapy. To undertake exploratory model-based cost-effectiveness analysis on the use of PFTs. DATA SOURCES: Bibliographic databases (e.g. MEDLINE from inception and EMBASE from 1980), conference proceedings and ongoing trial registries up to April 2012. METHODS: Standard systematic review methods were used for identifying clinical and cost studies. A risk-of-bias assessment tool was adapted from checklists for prognostic and diagnostic studies. (Un)adjusted odds and hazard ratios for the association between 'aspirin resistance', for different PFTs, and clinical outcomes are presented; however, heterogeneity between studies precluded pooling of results. A speculative economic model of a PFT and change of therapy strategy was developed. RESULTS: One hundred and eight relevant studies using a variety of PFTs, 58 in patients on aspirin monotherapy, were analysed in detail. Results indicated that some PFTs may have some prognostic utility, i.e. a trend for more clinical events to be associated with groups classified as 'aspirin resistant'. Methodological and clinical heterogeneity prevented a quantitative summary of prognostic effect. Study-level effect sizes were generally small and absolute outcome risk was not substantially different between 'aspirin resistant' and 'aspirin sensitive' designations. No studies on the cost-effectiveness of PFTs for 'aspirin resistance' were identified. Based on assumptions of PFTs being able to accurately identify patients at high risk of clinical events and such patients benefiting from treatment modification, the economic model found that a test-treat strategy was likely to be cost-effective. However, neither assumption is currently evidence based. LIMITATIONS: Poor or incomplete reporting of studies suggests a potentially large volume of inaccessible data. Analyses were confined to studies on patients prescribed aspirin as sole antiplatelet therapy at the time of PFT. Clinical and methodological heterogeneity across studies precluded meta-analysis. Given the lack of robust data the economic modelling was speculative. CONCLUSIONS: Although evidence indicates that some PFTs may have some prognostic value, methodological and clinical heterogeneity between studies and different approaches to analyses create confusion and inconsistency in prognostic results, and prevented a quantitative summary of their prognostic effect. Protocol-driven and adequately powered primary studies are needed, using standardised methods of measurements to evaluate the prognostic ability of each test in the same population(s), and ideally presenting individual patient data. For any PFT to inform individual risk prediction, it will likely need to be considered in combination with other prognostic factors, within a prognostic model. STUDY REGISTRATION: This study is registered as PROSPERO 2012:CRD42012002151. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Supported self-management for patients with moderate to severe chronic obstructive pulmonary disease (COPD): an evidence synthesis and economic analysis.

BACKGROUND: Self-management (SM) support for patients with chronic obstructive pulmonary disease (COPD) is variable in its coverage, content, method and timing of delivery. There is insufficient evidence for which SM interventions are the most effective and cost-effective. OBJECTIVES: To undertake (1) a systematic review of the evidence for the effectiveness of SM interventions commencing within 6 weeks of hospital discharge for an exacerbation for COPD (review 1); (2) a systematic review of the qualitative evidence about patient satisfaction, acceptance and barriers to SM interventions (review 2); (3) a systematic review of the cost-effectiveness of SM support interventions within 6 weeks of hospital discharge for an exacerbation of COPD (review 3); (4) a cost-effectiveness analysis and economic model of post-exacerbation SM support compared with usual care (UC) (economic model); and (5) a wider systematic review of the evidence of the effectiveness of SM support, including interventions (such as pulmonary rehabilitation) in which there are significant components of SM, to identify which components are the most important in reducing exacerbations, hospital admissions/readmissions and improving quality of life (review 4). METHODS: The following electronic databases were searched from inception to May 2012: MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and Science Citation Index [Institute of Scientific Information (ISI)]. Subject-specific databases were also searched: PEDro physiotherapy evidence database, PsycINFO and the Cochrane Airways Group Register of Trials. Ongoing studies were sourced through the metaRegister of Current Controlled Trials, International Standard Randomised Controlled Trial Number database, World Health Organization International Clinical Trials Registry Platform Portal and ClinicalTrials.gov. Specialist abstract and conference proceedings were sourced through ISI's Conference Proceedings Citation Index and British Library's Electronic Table of Contents (Zetoc). Hand-searching through European Respiratory Society, the American Thoracic Society and British Thoracic Society conference proceedings from 2010 to 2012 was also undertaken, and selected websites were also examined. Title, abstracts and full texts of potentially relevant studies were scanned by two independent reviewers. Primary studies were included if ≈90% of the population had COPD, the majority were of at least moderate severity and reported on any intervention that included a SM component or package. Accepted study designs and outcomes differed between the reviews. Risk of bias for randomised controlled trials (RCTs) was assessed using the Cochrane tool. Random-effects meta-analysis was used to combine studies where appropriate. A Markov model, taking a 30-year time horizon, compared a SM intervention immediately following a hospital admission for an acute exacerbation with UC. Incremental costs and quality-adjusted life-years were calculated, with sensitivity analyses. RESULTS: From 13,355 abstracts, 10 RCTs were included for review 1, one study each for reviews 2 and 3, and 174 RCTs for review 4. Available studies were heterogeneous and many were of poor quality. Meta-analysis identified no evidence of benefit of post-discharge SM support on admissions [hazard ratio (HR) 0.78, 95% confidence interval (CI) 0.52 to 1.17], mortality (HR 1.07, 95% CI 0.74 to 1.54) and most other health outcomes. A modest improvement in health-related quality of life (HRQoL) was identified but this was possibly biased due to high loss to follow-up. The economic model was speculative due to uncertainty in impact on readmissions. Compared with UC, post-discharge SM support (delivered within 6 weeks of discharge) was more costly and resulted in better outcomes (£683 cost difference and 0.0831 QALY gain). Studies assessing the effect of individual components were few but only exercise significantly improved HRQoL (3-month St George's Respiratory Questionnaire 4.87, 95% CI 3.96 to 5.79). Multicomponent interventions produced an improved HRQoL compared with UC (mean difference 6.50, 95% CI 3.62 to 9.39, at 3 months). Results were consistent with a potential reduction in admissions. Interventions with more enhanced care from health-care professionals improved HRQoL and reduced admissions at 1-year follow-up. Interventions that included supervised or unsupervised structured exercise resulted in significant and clinically important improvements in HRQoL up to 6 months. LIMITATIONS: This review was based on a comprehensive search strategy that should have identified most of the relevant studies. The main limitations result from the heterogeneity of studies available and widespread problems with their design and reporting. CONCLUSIONS: There was little evidence of benefit of providing SM support to patients shortly after discharge from hospital, although effects observed were consistent with possible improvement in HRQoL and reduction in hospital admissions. It was not easy to tease out the most effective components of SM support packages, although interventions containing exercise seemed the most effective. Future work should include qualitative studies to explore barriers and facilitators to SM post exacerbation and novel approaches to affect behaviour change, tailored to the individual and their circumstances. Any new trials should be properly designed and conducted, with special attention to reducing loss to follow-up. Individual participant data meta-analysis may help to identify the most effective components of SM interventions. STUDY REGISTRATION: This study is registered as PROSPERO CRD42011001588. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Outpatient versus inpatient uterine polyp treatment for abnormal uterine bleeding: randomised controlled non-inferiority study.

OBJECTIVE: To compare the effectiveness and acceptability of outpatient polypectomy with inpatient polypectomy. DESIGN: Pragmatic multicentre randomised controlled non-inferiority study. SETTING: Outpatient hysteroscopy clinics in 31 UK National Health Service hospitals. PARTICIPANTS: 507 women who attended as outpatients for diagnostic hysteroscopy because of abnormal uterine bleeding and were found to have uterine polyps. INTERVENTIONS: Participants were randomly assigned to either outpatient uterine polypectomy under local anaesthetic or inpatient uterine polypectomy under general anaesthesia. Data were collected on women's self reported bleeding symptoms at baseline and at 6, 12, and 24 months. Data were also collected on pain and acceptability of the procedure at the time of polypectomy. MAIN OUTCOME MEASURES: The primary outcome was successful treatment, determined by the women's assessment of bleeding at six months, with a prespecified non-inferiority margin of 25%. Secondary outcomes included generic (EQ-5D) and disease specific (menorrhagia multi-attribute scale) quality of life, and feasibility and acceptability of the procedure. RESULTS: 73% (166/228) of women in the outpatient group and 80% (168/211) in the inpatient group reported successful treatment at six months (intention to treat relative risk 0.91, 95% confidence interval 0.82 to 1.02; per protocol relative risk 0.92, 0.82 to 1.02). Failure to remove polyps was higher (19% v 7%; relative risk 2.5, 1.5 to 4.1) and acceptability of the procedure was lower (83% v 92%; 0.90, 0.84 to 0.97) in the outpatient group Quality of life did not differ significantly between the groups. Four uterine perforations, one of which necessitated bowel resection, all occurred in the inpatient group. CONCLUSIONS: Outpatient polypectomy was non-inferior to inpatient polypectomy. Failure to remove a uterine polyp was, however, more likely with outpatient polypectomy and acceptability of the procedure was slightly lower. TRIAL REGISTRATION: International Clinical Trials Registry 65868569.

A multicentre, pragmatic, parallel group, randomised controlled trial to compare the clinical and cost-effectiveness of three physiotherapy-led exercise interventions for knee osteoarthritis in older adults: the BEEP trial protocol (ISRCTN: 93634563).

BACKGROUND: Exercise is consistently recommended for older adults with knee pain related to osteoarthritis. However, the effects from exercise are typically small and short-term, likely linked to insufficient individualisation of the exercise programme and limited attention to supporting exercise adherence over time. The BEEP randomised trial aims to improve patients' short and long-term outcomes from exercise. It will test the overall effectiveness and cost-effectiveness of two physiotherapy-led exercise interventions (Individually Tailored Exercise and Targeted Exercise Adherence) to improve the individual tailoring of, and adherence to exercise, compared with usual physiotherapy care. METHODS/DESIGN: Based on the learning from a pilot study (ISRCTN 23294263), the BEEP trial is a multi-centre, pragmatic, parallel group, individually randomised controlled trial, with embedded longitudinal qualitative interviews. 500 adults in primary care, aged 45 years and over with knee pain will be randomised to 1 of 3 treatment groups delivered by fully trained physiotherapists in up to 6 NHS services. These are: Usual Physiotherapy Care (control group consisting of up to 4 treatment sessions of advice and exercise), Individually Tailored Exercise (an individualised, supervised and progressed lower-limb exercise programme) or Targeted Exercise Adherence (supporting patients to adhere to exercise and to engage in general physical activity over the longer-term). The primary outcomes are pain and function as measured by the Western Ontario and McMaster Osteoarthritis index. A comprehensive range of secondary outcomes are also included. Outcomes are measured at 3, 6 (primary outcome time-point), 9, 18 and 36 months. Data on adverse events will also be collected. Semi-structured, qualitative interviews with a subsample of 30 participants (10 from each treatment group) will be undertaken at two time-points (end of treatment and 12 to 18 months later) and analysed thematically. DISCUSSION: This trial will contribute to the evidence base for management of older adults with knee pain attributable to osteoarthritis in primary care. The findings will have important implications for healthcare commissioners, general practitioners and physiotherapy service providers and it will inform future education of healthcare practitioners. It may also serve to delay or prevent some individuals from becoming surgical candidates. TRIAL REGISTRATION ISRCTN: ISRCTN93634563.