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Objectives Health economics analysis plans (HEAPs) currently lack consistency, with uncertainty surrounding appropriate content. We aimed to develop a list of essential items that should be included in HEAPs for economic evaluations conducted alongside randomized trials. Methods A list of potential items for inclusion was developed by examining existing HEAPs. An electronic Delphi survey was conducted among professional health economists. Respondents were asked to rate potential items from 1 (least important) to 9 (most important), suggest additional items, and comment on proposed items (round 1). A second survey (round 2) was emailed to participants, including the participant’s own scores from round 1 along with summary results from the whole panel; participants were asked to rerate each item. Consensus criteria for inclusion in the final list were predefined as >70% of participants rating an item 7-9 and, Highlights • Health economics analysis plans (HEAPs) are becoming best practice for economic evaluations conducted alongside randomized controlled trials; however, they are currently implemented inconsistently. • This study used Delphi consensus techniques to identify a list of items that should be included in a HEAP. • A standardized HEAP will contribute to the transparency and reproducibility of economic evaluations and to the minimization of bias.

Objective To determine the cost-effectiveness of the current gold standard operation of transurethral resection of the prostate (TURP) compared to the new laser technique of thulium laser transurethral vaporesection of the prostate (ThuVARP) in men with benign prostatic obstruction (BPO) within the United Kingdom (UK) National Health Service (NHS). Patients and methods The trial was conducted across seven UK centres (four university teaching hospitals and three district general hospitals). 410 men aged 18 years and older presenting with either bothersome lower urinary tract symptoms (LUTS) or urinary retention secondary to BPO, and suitable for surgery, were randomised (whilst under anaesthetic) 1:1 to receive the TURP or ThuVARP procedure. Resource use in relation to the operation, initial inpatient stay, and subsequent use of NHS services was collected for 12 months from randomisation (equivalent to primary effectiveness outcome) using hospital records and patient questionnaires. Resources were valued using UK reference costs. QALYs (quality adjusted life years) were calculated from the EQ-5D-5L questionnaire completed at baseline, 3- and 12-months. Total adjusted mean costs, QALYs and incremental Net Monetary Benefit statistics were calculated: cost-effectiveness acceptability curves and sensitivity analyses addressed uncertainty. Results The total adjusted mean secondary care cost over the 12 months in the TURP arm (£4244) was £9 (95% CI of -£376 to £359) lower than the ThuVARP arm (£4253). The ThuVARP operation took on average 21 minutes longer than TURP. The adjusted mean difference of Quality Adjusted Life Years (QALYs) (0.01 favouring TURP, 95% CI of -0.01 to 0.04) was similar between the arms. There is a 76% probability that TURP is the cost-effective option compared with ThuVARP at the £20,000 per QALY willingness to pay threshold used by National Institute for Health and Care Excellence (NICE). Conclusion One of the anticipated benefits of the laser surgery, reduced length of hospital stay with an associated reduction in cost, did not materialise within the study. The longer duration of the ThuVARP procedure is important to consider, both from a patient perspective in terms of increased time under anaesthetic, and from a service delivery perspective. TURP remains a highly cost-effective treatment for men with BPO.

Background Acute otitis media is a painful infection of the middle ear that is commonly seen in children. In some children, the eardrum spontaneously bursts, discharging visible pus (otorrhoea) into the outer ear. Objective To compare the clinical effectiveness of immediate topical antibiotics or delayed oral antibiotics with the clinical effectiveness of immediate oral antibiotics in reducing symptom duration in children presenting to primary care with acute otitis media with discharge and the economic impact of the alternative strategies. Design This was a pragmatic, three-arm, individually randomised (stratified by age Setting A total of 44 English general practices. Participants Children aged ≥ 12 months and Interventions (1) Immediate ciprofloxacin (0.3%) solution, four drops given three times daily for 7 days, or (2) delayed ‘dose-by-age’ amoxicillin suspension given three times daily (clarithromycin twice daily if the child was penicillin allergic) for 7 days, with structured delaying advice. All parents were given standardised information regarding symptom management (paracetamol/ibuprofen/fluids) and advice to complete the course. Comparator Immediate ‘dose-by-age’ oral amoxicillin given three times daily (or clarithromycin given twice daily) for 7 days. Parents received standardised symptom management advice along with advice to complete the course. Main outcome measure Time from randomisation to the first day on which all symptoms (pain, fever, being unwell, sleep disturbance, otorrhoea and episodes of distress/crying) were rated ‘no’ or ‘very slight’ problem (without need for analgesia). Methods Participants were recruited from routine primary care appointments. The planned sample size was 399 children. Follow-up used parent-completed validated symptom diaries. Results Delays in software deployment and configuration led to small recruitment numbers and trial closure at the end of the internal pilot. Twenty-two children (median age 5 years; 62% boys) were randomised: five, seven and 10 to immediate oral, delayed oral and immediate topical antibiotics, respectively. All children received prescriptions as randomised. Seven (32%) children fully adhered to the treatment as allocated. Symptom duration data were available for 17 (77%) children. The median (interquartile range) number of days until symptom resolution in the immediate oral, delayed oral and immediate topical antibiotic arms was 6 (4–9), 4 (3–7) and 4 (3–6), respectively. Comparative analyses were not conducted because of small numbers. There were no serious adverse events and six reports of new or worsening symptoms. Qualitative clinician interviews showed that the trial question was important. When the platform functioned as intended, it was liked. However, staff reported malfunctioning software for long periods, resulting in missed recruitment opportunities. Troubleshooting the software placed significant burdens on staff. Limitations The over-riding weakness was the failure to recruit enough children. Conclusions We were unable to answer the main research question because of a failure to reach the required sample size. Our experience of running an electronic platform-supported trial in primary care has highlighted challenges from which we have drawn recommendations for the National Institute for Health Research (NIHR) and the research community. These should be considered before such a platform is used again. Trial registration Current Controlled Trials ISRCTN12873692 and EudraCT 2017-003635-10. Funding This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 67. See the NIHR Journals Library website for further project information.

Background Lower urinary tract symptoms (LUTS) can relate to urinary storage or voiding. In men, the prevalence and severity of LUTS increases with age, with a significant impact on quality of life. The majority of men presenting with LUTS are managed by their general practitioner (GP) in the first instance, with conservative therapies recommended as the initial treatment. However, the provision of conservative therapies in primary care is variable and can be time and resource limited. GPs require practical resources to enhance patient engagement with such interventions. TRIUMPH aims to determine whether a standardised and manualised care intervention delivered in primary care achieves superior symptomatic outcome for LUTS versus usual care. Methods/design TRIUMPH is a two-arm, cluster randomised controlled trial (RCT) being conducted in 30 National Health Service (NHS) general practices in England. The TRIUMPH intervention comprises a standardised LUTS advice booklet developed for the trial with patient and healthcare professional (HCP) consultation. The booklet is delivered to patients by nurses/healthcare assistants following assessment of their urinary symptoms. Patients are directed to relevant sections of the booklet, providing the manualised element of the intervention. To encourage adherence, HCPs provide follow-up contacts over 12 weeks. Practices are randomised 1:1 to either deliver the TRIUMPH intervention or a usual care pathway. The patient-reported International Prostate Symptom Score (IPSS) at 12 months post consent is the primary outcome. Secondary outcomes include cost-effectiveness, patient-reported outcomes on LUTS, quality of life, and patient and HCP acceptability and experience of the intervention. Primary analyses will be conducted on an intention-to-treat basis. Discussion It is unclear whether conservative therapies for male LUTS are effectively delivered in primary care using current approaches. This can lead to men being inappropriately referred to secondary care or experiencing persistent symptoms. Primary care, therefore, holds the key to effective treatment for these men. The TRIUMPH intervention, through its standardised and manualised approach, has been developed to support GP practices in delivering effective conservative care. This pragmatic, cluster RCT should provide robust evidence in a primary-care setting to inform future guidelines. Trial registration ISCRTN registry, ID: ISRCTN11669964. Registered on 12 April 2018. Electronic supplementary material The online version of this article (10.1186/s13063-019-3648-1) contains supplementary material, which is available to authorized users.

Background While the methods for conducting health economics research in general are improving, current guidelines provide limited guidance regarding resource use measurement (RUM). Consequently, a variety of methods exists, yet there is no overview of aspects to consider when deciding on the most appropriate RUM methodology. Therefore, this study aims to (1) identify and categorize existing knowledge regarding aspects of RUM, and (2) develop a framework that provides a comprehensive overview of methodological aspects regarding RUM. Methods Relevant articles were identified by enrolling a search string in six databases and handsearching the DIRUM database. Included articles were descriptively reviewed and served as input for a comprehensive framework. Health economics experts were involved during the process to establish the framework’s face validity. Results Forty articles were included in the scoping review. The RUM framework consists of four methodological RUM domains: ‘Whom to measure’, addressing whom to ask and whom to measure; ‘How to measure’, addressing the different approaches of measurement; ‘How often to measure’, addressing recall period and measurement patterns; and ‘Additional considerations’, which covers additional aspects that are essential for further refining the methodologies for measurement. Evidence retrieved from the scoping review was categorized according to these domains. Conclusion This study clustered the aspects of RUM methodology in health economics into a comprehensive framework. The results may guide health economists in their decision making regarding the selection of appropriate RUM methods and developing instruments for RUM. Furthermore, policy makers may use these findings to review study results from an evidence-based perspective. Supplementary Information The online version contains supplementary material available at 10.1007/s40273-021-01048-z.

Background Prosthetic joint infection (PJI) following total hip replacement (THR) surgery is a serious complication that negatively impacts patients’ lives and is financially burdensome for healthcare providers. As the number of THRs increases, so does this financial burden. This research estimates the economic burden with respect to inpatient and day case hospital admissions for patients receiving revision surgery for PJI following primary THR. Methods In this matched cohort study, the National Joint Registry for England, Wales, Northern Ireland and the Isle of Man (NJR) was used to identify patients. Patients revised for PJI with a one- or two-stage revision following THR and patients not revised for PJI were matched on several characteristics using exact and radius matching. Hospital inpatient and day case healthcare records from the English Hospital Episode Statistics database were obtained for 5 years following the identified patient’s primary THR. UK national unit costs were applied to hospital admissions and the 5-year total cost was estimated. A two-part model (Probit and generalised linear model) was employed to estimate the incremental difference in costs between those revised and not revised for PJI. Results Between 2006 and 2009, 1914 revisions for PJI were identified in the NJR. The matching resulted in 422 patients revised for PJI and 1923 matches not revised for PJI who were included in the analysis. The average cost of inpatient and day case admissions in the 5 years following primary THR was approximately £42,000 for patients revised for PJI and £8000 for patients not revised for PJI. The difference in costs over the 5 years was £33,452 (95% CI £30,828 to £36,077; p Conclusions In the 5 years following primary THR, patients who develop PJI and have revision surgery cost approximately £33,000 (over 5-fold) more than patients not revised for PJI based on their hospital inpatient and day case admissions alone. The total burden of PJI is likely to be much higher when also considering outpatient, primary and community care costs. This highlights the need to find both ways to reduce the incidence of PJI following THR and cost-effective treatment strategies if PJI occurs.

Background Transurethral resection of the prostate (TURP) is the standard operation for benign prostatic obstruction (BPO). Thulium laser transurethral vaporesection of the prostate (ThuVARP) vaporises and resects the prostate using a technique similar to TURP. The small amount of existing literature suggests that there may be potential advantages of ThuVARP over TURP. Objective To determine whether or not the outcomes from ThuVARP are equivalent to the outcomes from TURP in men with BPO treated in the NHS. Design A multicentre, pragmatic, randomised controlled parallel-group trial, with an embedded qualitative study and economic evaluation. Setting Seven UK centres – four university teaching hospitals and three district general hospitals. Participants Men aged ≥ 18 years who were suitable to undergo TURP, presenting with bothersome lower urinary tract symptoms (LUTS) or urinary retention secondary to BPO. Interventions Patients were randomised 1 : 1 to receive TURP or ThuVARP and remained blinded. Main outcome measures Two co-primary outcomes – patient-reported International Prostate Symptom Score (IPSS) and clinical measure of maximum urine flow rate (Qmax) at 12 months post surgery. Results In total, 410 men were randomised, 205 to each arm. The two procedures were equivalent in terms of IPSS [adjusted mean difference 0.28 points higher for ThuVARP (favouring TURP), 95% confidence interval (CI) –0.92 to 1.49 points]. The two procedures were not equivalent in terms of Qmax (adjusted mean difference 3.12 ml/second in favour of TURP, 95% CI 0.45 to 5.79 ml/second), with TURP deemed superior. Surgical outcomes, such as complications and blood transfusion rates, and hospital stay were similar for both procedures. Patient-reported urinary and sexual symptoms were also similar between the arms. Qualitative interviews indicated similar patient experiences with both procedures. However, 25% of participants in the ThuVARP arm did not undergo their randomised allocation, compared with 2% of participants in the TURP arm. Prostate cancer was also detected less frequently from routine histology after ThuVARP (65% lower odds of detection) in an exploratory analysis. The adjusted mean differences between the arms were similar for secondary care NHS costs (£9 higher for ThuVARP, 95% CI –£359 to £376) and quality-adjusted life-years (0.01 favouring TURP, 95% CI –0.04 to 0.01). Limitations Complications were recorded in prespecified categories; those not prespecified were excluded owing to variable reporting. Preoperative Qmax and IPSS data could not be collected for participants with indwelling catheters, making adjustment for baseline status difficult. Conclusions TURP was superior to ThuVARP in terms of Qmax, although both operations resulted in a Qmax considered clinically successful. ThuVARP also potentially resulted in lower detection rates of prostate cancer as a result of the smaller volume of tissue available for histology. Length of hospital stay after ThuVARP, anticipated to be a key benefit, was equal to that after TURP in this trial. Overall, both ThuVARP and TURP were effective procedures for BPO, with minor benefits in favour of TURP. Therefore, the results suggest that it may be appropriate that new treatment alternatives continue to be compared with TURP. Future work Longer-term follow-up to assess reoperation rates over time, and research into the comparative effectiveness of ThuVARP and TURP in large prostates. Trial registration Current Controlled Trials ISRCTN00788389. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 41. See the NIHR Journals Library website for further project information.

ObjectiveProstate surgery can improve lower urinary tract symptoms (LUTS) by relieving bladder outlet obstruction (BOO). However, surgery is less effective without BOO, or if detrusor underactivity (DU) is present. Urodynamics (UDS) can identify BOO and measure detrusor activity, but evidence in clinical practice is lacking. UPSTREAM (Urodynamics for Prostate Surgery Trial: Randomised Evaluation of Assessment Methods) evaluated whether a carepathway including UDS would reduce surgery without increasing urinary symptoms.Design, setting and participantsUPSTREAM is a pragmatic, non-inferiority randomised controlled trial in 26 hospitals in England (ISRCTN56164274) in men with bothersome LUTS where surgery was an option. InterventionParticipants were randomised (1:1) to routine care (RC) diagnostic tests, or routine care plus urodynamics (UDS).Outcome measuresThe primary outcome was International Prostate Symptom Score (IPSS; patient reported outcome scale from 0 to 35 points) 18-months post-randomisation, with a non-inferiority margin of one point. Urological surgery rates were a key secondary outcome.Statistical analysisThe primary outcome was compared between the arms using linear regression, analysed on an intention-to-treat basis.Results and limitationsBetween October 2014 and December 2016, 820 men (median age 68 years) were randomised (393 and 427 in RC and UDS arms, respectively). The UDS arm showed noninferiority of mean IPSS scores (UDS 12·6; RC 13.1; adjusted difference at 18 months -0·33 (95% CI -1·47, +0·80)). In the UDS arm, 153/408 (38%) received surgery compared with 138/384 (36%) for RC (adjusted OR 1·05; 95% CI 0·77, 1·43). 428 adverse events (UDS 234; RC 194) were recorded, with related events similar in both arms, and 11 unrelated deaths.Conclusion In this population, the UDS randomised group was non-inferior to RC for IPSS but did not reduce surgical rates. The study shows that routine use of UDS in evaluation of uncomplicated LUTS has a limited role and should be used selectively. Patient summaryFor men with uncomplicated lower urinary tract symptoms, the symptom improvements after treatment and the number of operations done are similar, whether or not urodynamic tests aredone in addition to routine tests. Accordingly, routine use of UDS has a limited role in this population group.

Background Optimal management strategies for clinically localised prostate cancer are debated. Using median 10-year data from the largest randomised controlled trial to date (ProtecT), the lifetime cost-effectiveness of three major treatments (radical radiotherapy, radical prostatectomy and active monitoring) was explored according to age and risk subgroups. Methods A decision-analytic (Markov) model was developed and informed by clinical input. The economic evaluation adopted a UK NHS perspective and the outcome was cost per Quality-Adjusted Life Year (QALY) gained (reported in UK£), estimated using EQ-5D-3L. Results Costs and QALYs extrapolated over the lifetime were mostly similar between the three randomised strategies and their subgroups, but with some important differences. Across all analyses, active monitoring was associated with higher costs, probably associated with higher rates of metastatic disease and changes to radical treatments. When comparing the value of the strategies (QALY gains and costs) in monetary terms, for both low-risk prostate cancer subgroups, radiotherapy generated the greatest net monetary benefit (£293,446 [95% CI £282,811 to £299,451] by D’Amico and £292,736 [95% CI £284,074 to £297,719] by Grade group 1). However, the sensitivity analysis highlighted uncertainty in the finding when stratified by Grade group, as radiotherapy had 53% probability of cost-effectiveness and prostatectomy had 43%. In intermediate/high risk groups, using D’Amico and Grade group > = 2, prostatectomy generated the greatest net monetary benefit (£275,977 [95% CI £258,630 to £285,474] by D’Amico and £271,933 [95% CI £237,864 to £287,784] by Grade group). This finding was supported by the sensitivity analysis. Prostatectomy had the greatest net benefit (£290,487 [95% CI £280,781 to £296,281]) for men younger than 65 and radical radiotherapy (£201,311 [95% CI £195,161 to £205,049]) for men older than 65, but sensitivity analysis showed considerable uncertainty in both findings. Conclusion Over the lifetime, extrapolating from the ProtecT trial, radical radiotherapy and prostatectomy appeared to be cost-effective for low risk prostate cancer, and radical prostatectomy for intermediate/high risk prostate cancer, but there was uncertainty in some estimates. Longer ProtecT trial follow-up is required to reduce uncertainty in the model. Trial registration Current Controlled Trials number, ISRCTN20141297: http://isrctn.org (14/10/2002); ClinicalTrials.gov number, NCT02044172: http://www.clinicaltrials.gov (23/01/2014).

Background Self-report resource-use measures (RUMs) are often used to collect healthcare use data from participants in healthcare studies. However, RUMs are typically adapted from existing measures on a study-by-study basis, resulting in a lack of standardisation which limits comparability across studies. Psychometric testing of RUMs is rarely conducted. This paper reports on cognitive interviews with patients to test the content validity and acceptability of a new RUM (ModRUM). ModRUM is a brief, generic RUM with a core module on healthcare use and questions/modules to increase depth and breadth. Methods A purposeful sampling strategy with maximum variation was used to recruit patients from primary care to participate in “think-aloud” interviews with retrospective probing. Participants verbalised their thought processes as they completed ModRUM, which allowed errors (issues with completion) to be identified. The interviewer asked follow-up and probing questions to investigate errors, clarity and acceptability. Interviews were audio-recorded and transcribed verbatim. Research team members independently scored transcripts to identify errors in comprehension, recall, judgement and response. Members met to agree on final scores. Interview transcripts were analysed qualitatively using techniques of constant comparison, to identify common themes and ideas for improvement. Data collection and analysis were performed concurrently and in rounds. Results Twenty participants were interviewed between December 2019 and March 2020. Interviews were conducted in three rounds, with revisions made iteratively and in response to interview findings. Seven participants completed the core module and 13 completed the core module plus depth questions. Of 71 issues, 28 were in comprehension, 14 in retrieval, 10 in judgement, 18 in response and 1 uncategorised. Most issues (21 issues by 2 participants) were due to participants including family healthcare use. Other issues included using incorrect recall periods (5 issues) and overlooking questions leading to missing responses (9 issues). Common participant suggestions included highlighting important details and providing additional definition or examples for some terms. The length, content and layout were acceptable to most participants. Conclusions A generic RUM is needed to increase study comparability. RUM development requires thorough testing to demonstrate and enhance validity. Cognitive interviewing has demonstrated the acceptability and content validity of ModRUM.

Background Lower urinary tract symptoms (LUTS) in men may indicate bladder outlet obstruction (BOO) or weakness, known as detrusor underactivity (DU). Severe bothersome LUTS are a common indication for surgery. The diagnostic tests may include urodynamics (UDS) to confirm whether BOO or DU is the cause, potentially reducing the number of people receiving (inappropriate) surgery. Objectives The primary objective was to determine whether a care pathway including UDS is no worse for symptom outcome than one in which it is omitted, at 18 months after randomisation. Rates of surgery was the key secondary outcome. Design This was a pragmatic, multicentre, two-arm (unblinded) randomised controlled trial, incorporating a health economic analysis and qualitative research. Setting Urology departments of 26 NHS hospitals in England. Participants Men (aged ≥ 18 years) seeking further treatment, potentially including surgery, for bothersome LUTS. Exclusion criteria were as follows: unable to pass urine without a catheter, having a relevant neurological disease, currently undergoing treatment for prostate or bladder cancer, previously had prostate surgery, not medically fit for surgery and/or unwilling to be randomised. Interventions Men were randomised to a care pathway based on non-invasive routine tests (control) or routine care plus invasive UDS (intervention arm). Main outcome measures The primary outcome was International Prostate Symptom Score (IPSS) at 18 months after randomisation and the key secondary outcome was rates of surgery. Additional secondary outcomes included adverse events (AEs), quality of life, urinary and sexual symptoms, UDS satisfaction, maximum urinary flow rate and cost-effectiveness. Results A total of 820 men were randomised (UDS, 427; routine care, 393). Sixty-seven men withdrew before 18 months and 11 died (unrelated to trial procedures). UDS was non-inferior to routine care for IPSS 18 months after randomisation, with a confidence interval (CI) within the margin of 1 point (–0.33, 95% CI –1.47 to 0.80). A lower surgery rate in the UDS arm was not found (38% and 36% for UDS and routine care, respectively), with overall rates lower than expected. AEs were similar between the arms at 43–44%. There were more cases of acute urinary retention in the routine care arm. Patient-reported outcomes for LUTS improved in both arms and satisfaction with UDS was high in men who received it. UDS was more expensive than routine care. From a secondary care perspective, UDS cost an additional £216 over an 18-month time horizon. Quality-adjusted life-years (QALYs) were similar, with a QALY difference of 0.006 in favour of UDS over 18 months. It was established that UDS was acceptable to patients, and valued by both patients and clinicians for its perceived additional insight into the cause and probable best treatment of LUTS. Limitations The trial met its predefined recruitment target, but surgery rates were lower than anticipated. Conclusions Inclusion of UDS in the diagnostic tests results in a symptom outcome that is non-inferior to a routine care pathway, but does not affect surgical rates for treating BOO. Results do not support the routine use of UDS in men undergoing investigation of LUTS. Future work Focus should be placed on indications for selective utilisation of UDS in individual cases and long-term outcomes of diagnosis and therapy. Trial registration Current Controlled Trials ISRCTN56164274. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 42. See the NIHR Journals Library website for further project information.

Background Prostate cancer is the most common cancer among men in the UK. Prostate-specific antigen testing followed by biopsy leads to overdetection, overtreatment as well as undertreatment of the disease. Evidence of treatment effectiveness has lacked because of the paucity of randomised controlled trials comparing conventional treatments. Objectives To evaluate the effectiveness of conventional treatments for localised prostate cancer (active monitoring, radical prostatectomy and radical radiotherapy) in men aged 50–69 years. Design A prospective, multicentre prostate-specific antigen testing programme followed by a randomised trial of treatment, with a comprehensive cohort follow-up. Setting Prostate-specific antigen testing in primary care and treatment in nine urology departments in the UK. Participants Between 2001 and 2009, 228,966 men aged 50–69 years received an invitation to attend an appointment for information about the Prostate testing for cancer and Treatment (ProtecT) study and a prostate-specific antigen test; 82,429 men were tested, 2664 were diagnosed with localised prostate cancer, 1643 agreed to randomisation to active monitoring (n = 545), radical prostatectomy (n = 553) or radical radiotherapy (n = 545) and 997 chose a treatment. Interventions The interventions were active monitoring, radical prostatectomy and radical radiotherapy. Trial primary outcome measure Definite or probable disease-specific mortality at the 10-year median follow-up in randomised participants. Secondary outcome measures Overall mortality, metastases, disease progression, treatment complications, resource utilisation and patient-reported outcomes. Results There were no statistically significant differences between the groups for 17 prostate cancer-specific (p = 0.48) and 169 all-cause (p = 0.87) deaths. Eight men died of prostate cancer in the active monitoring group (1.5 per 1000 person-years, 95% confidence interval 0.7 to 3.0); five died of prostate cancer in the radical prostatectomy group (0.9 per 1000 person-years, 95% confidence interval 0.4 to 2.2 per 1000 person years) and four died of prostate cancer in the radical radiotherapy group (0.7 per 1000 person-years, 95% confidence interval 0.3 to 2.0 per 1000 person years). More men developed metastases in the active monitoring group than in the radical prostatectomy and radical radiotherapy groups: active monitoring, n = 33 (6.3 per 1000 person-years, 95% confidence interval 4.5 to 8.8); radical prostatectomy, n = 13 (2.4 per 1000 person-years, 95% confidence interval 1.4 to 4.2 per 1000 person years); and radical radiotherapy, n = 16 (3.0 per 1000 person-years, 95% confidence interval 1.9 to 4.9 per 1000 person-years; p = 0.004). There were higher rates of disease progression in the active monitoring group than in the radical prostatectomy and radical radiotherapy groups: active monitoring (n = 112; 22.9 per 1000 person-years, 95% confidence interval 19.0 to 27.5 per 1000 person years); radical prostatectomy (n = 46; 8.9 per 1000 person-years, 95% confidence interval 6.7 to 11.9 per 1000 person-years); and radical radiotherapy (n = 46; 9.0 per 1000 person-years, 95% confidence interval 6.7 to 12.0 per 1000 person years; p Limitations A single prostate-specific antigen test and transrectal ultrasound biopsies were used. There were very few non-white men in the trial. The majority of men had low- and intermediate-risk disease. Longer follow-up is needed. Conclusions At a median follow-up point of 10 years, prostate cancer-specific mortality was low, irrespective of the assigned treatment. Radical prostatectomy and radical radiotherapy reduced disease progression and metastases, but with side effects. Further work is needed to follow up participants at a median of 15 years. Trial registration Current Controlled Trials ISRCTN20141297. Funding This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 37. See the National Institute for Health Research Journals Library website for further project information.

Summary Background Transurethral resection of the prostate (TURP) is the standard operation for benign prostatic obstruction. Thulium laser transurethral vaporesection of the prostate (ThuVARP) is a technique with suggested advantages over TURP, including reduced complications and hospital stay. We aimed to investigate TURP versus ThuVARP in men with lower urinary tract symptoms or urinary retention secondary to benign prostatic obstruction. Methods In this randomised, blinded, parallel-group, pragmatic equivalence trial, men in seven UK hospitals with bothersome lower urinary tract symptoms or urinary retention secondary to benign prostatic obstruction were randomly assigned (1:1) at the point of surgery to receive ThuVARP or TURP. Patients were masked until follow-up completion. Centres used their usual TURP procedure (monopolar or bipolar). All trial surgeons underwent training on the ThuVARP technique. Co-primary outcomes were maximum urinary flow rate (Qmax) and International Prostate Symptom Score (IPSS) at 12-months post-surgery. Equivalence was defined as a difference of 2·5 points or less for IPSS and 4 mL per s or less for Qmax. Analysis was done according to the intention-to-treat principle. The trial is registered with the ISRCTN Registry, ISRCTN00788389. Findings Between July 23, 2014, and Dec 30, 2016, 410 men were randomly assigned to ThuVARP or TURP, 205 per study group. TURP was superior for Qmax (mean 23·2 mL per s for TURP and 20·2 mL per s for ThuVARP; adjusted difference in means −3·12, 95% CI −5·79 to −0·45). Equivalence was shown for IPSS (mean 6·3 for TURP and 6·4 for ThuVARP; adjusted difference in means 0·28, −0·92 to 1·49). Mean hospital stay was 48 h in both study groups. 91 (45%) of 204 patients in the TURP group and 96 (47%) of 203 patients in the ThuVARP group had at least one complication. Interpretation TURP and ThuVARP were equivalent for urinary symptom improvement (IPSS) 12-months post-surgery, and TURP was superior for Qmax. Anticipated laser benefits for ThuVARP of reduced hospital stay and complications were not observed. Funding UK National Institute for Health Research Health Technology Assessment Programme.

Background There is limited evidence relating to the cost-effectiveness of treatments for localised prostate cancer. Methods The cost-effectiveness of active monitoring, surgery, and radiotherapy was evaluated within the Prostate Testing for Cancer and Treatment (ProtecT) randomised controlled trial from a UK NHS perspective at 10 years’ median follow-up. Prostate cancer resource-use collected from hospital records and trial participants was valued using UK reference-costs. QALYs (quality-adjusted-life-years) were calculated from patient-reported EQ-5D-3L measurements. Adjusted mean costs, QALYs, and incremental cost-effectiveness ratios were calculated; cost-effectiveness acceptability curves and sensitivity analyses addressed uncertainty; subgroup analyses considered age and disease-risk. Results Adjusted mean QALYs were similar between groups: 6.89 (active monitoring), 7.09 (radiotherapy), and 6.91 (surgery). Active monitoring had lower adjusted mean costs (£5913) than radiotherapy (£7361) and surgery (£7519). Radiotherapy was the most likely (58% probability) cost-effective option at the UK NICE willingness-to-pay threshold (£20,000 per QALY). Subgroup analyses confirmed radiotherapy was cost-effective for older men and intermediate/high-risk disease groups; active monitoring was more likely to be the cost-effective option for younger men and low-risk groups. Conclusions Longer follow-up and modelling are required to determine the most cost-effective treatment for localised prostate cancer over a man’s lifetime. Trial registration Current Controlled Trials number, ISRCTN20141297: http://isrctn.org (14/10/2002); ClinicalTrials.gov number, NCT02044172: http://www.clinicaltrials.gov (23/01/2014).

Background Clinical evaluation of male lower urinary tract symptoms (MLUTS) in secondary care uses a range of assessments. It is unknown how MLUTS evaluation influences outcome of therapy recommendations and choice, notably urodynamics (UDS; filling cystometry and pressure flow studies). Objective To report participants’ sociodemographic and clinical characteristics, and initial diagnostic findings of the Urodynamics for Prostate Surgery Trial; Randomised Evaluation of Assessment Methods (UPSTREAM). UPSTREAM is a randomised controlled trial evaluating whether symptoms are noninferior and surgery rates are lower if UDS is included. Design, setting, and participants A total of 820 men (≥18 yr of age) seeking treatment for bothersome LUTS were recruited from 26 National Health Service hospital urology departments. Intervention Care pathway based on routine, noninvasive tests (control) or routine care plus UDS (intervention arm). Outcome measurements and statistical analysis The primary outcome is International Prostate Symptom Score (IPSS) and the key secondary outcome is surgery rates 18 mo after randomisation. International Consultation on Incontinence Questionnaires were captured for MLUTS, sexual function, and UDS satisfaction. Baseline clinical and patient-reported outcome measures (PROMs), and UDS findings were informally compared between arms. Trends across age groups for urinary and sexual PROMs were evaluated with a Cuzick’s test, and questionnaire items were compared using Pearson’s correlation coefficient. Results and limitations Storage LUTS, notably nocturia, and impaired sexual function are prominent in men being assessed for surgery. Sociodemographic and clinical evaluations were similar between arms. Overall mean IPSS and quality of life scores were 18.94 and 4.13, respectively. Trends were found across age groups, with older men suffering from higher rates of incontinence, nocturia, and erectile dysfunction, and younger men suffering from increased daytime frequency and voiding symptoms. Men undergoing UDS testing expressed high satisfaction with the procedure. Conclusions Men being considered for surgery have additional clinical features that may affect treatment decision making and outcomes, notably storage LUTS and impaired sexual function. Patient summary We describe initial assessment findings from a large clinical study of the treatment pathway for men suffering with bothersome urinary symptoms who were referred to hospital for further treatment, potentially including surgery. We report the patient characteristics and diagnostic test results, including symptom questionnaires, bladder diaries, flow rate tests, and urodynamics.

Aims: The treatment of prostate cancer has evolved markedly over the last 40 years, including radiotherapy, notably with escalated dose and targeting. However, the optimal treatment for localised disease has not been established in comparative randomised trials. The aim of this article is to describe the history ofprostate radiotherapy trials, including their quality assurance processes, and to compare these with the ProtecT trial.Materials and methods: The UK ProtecT randomised trial compares external beam conformal radiotherapy, surgery and active monitoring for clinically localized prostate cancer and will report on the primary outcome (disease-specific mortality) in 2016 following recruitment between 1999 and 2009. The embedded quality assurance programme consists of on-site machine dosimetry at the nine trial centres, a retrospective review of outlining and adherence to dose constraints based on the trial protocol in 54 participants (randomly selected, around 10% of the total randomised to radiotherapy, n ¼ 545). These quality assurance processes and results were compared with prostate radiotherapy trials of a comparable era.Results: There has been an increasingly sophisticated quality assurance programme in UK prostate radiotherapy trials over the last 15 years, reflecting dose escalation and treatment complexity. In ProtecT, machine dosimetry results were comparable between trial centres and with the UK RT01 trial. The outliningreview showed that most deviations were clinically acceptable, although three (1.4%) may have been of clinical significance and were related to outlining of theprostate. Seminal vesicle outlining varied, possibly due to several prostate trials running concurrently with different protocols. Adherence to dose constraints inProtecT was considered acceptable, with 80% of randomised participants having two or less deviations and planning target volume coverage was excellent.Conclusion: The ProtecT trial quality assurance results were satisfactory and comparable with trials of its era. Future trials should aim to standardise treatment protocols and quality assurance programmes where possible to reduce complexities for centres involved in multiple trials. 2016 Published by Elsevier Ltd on behalf of The Royal College of Radiologists.

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.

Background Approximately 20% of patients experience chronic pain after total knee replacement. There is little evidence for effective interventions for the management of this pain, and current healthcare provision is patchy and inconsistent. Given the complexity of this condition, multimodal and individualised interventions matched to pain characteristics are needed. We have undertaken a comprehensive programme of work to develop a care pathway for patients with chronic pain after total knee replacement. This protocol describes the design of a randomised controlled trial to evaluate the clinical- and cost-effectiveness of a complex intervention care pathway compared with usual care. Methods This is a pragmatic two-armed, open, multi-centred randomised controlled trial conducted within secondary care in the UK. Patients will be screened at 2 months after total knee replacement and 381 patients with chronic pain at 3 months postoperatively will be recruited. Recruitment processes will be optimised through qualitative research during a 6-month internal pilot phase. Patients are randomised using a 2:1 intervention:control allocation ratio. All participants receive usual care as provided by their hospital. The intervention comprises an assessment clinic appointment at 3 months postoperatively with an Extended Scope Practitioner and up to six telephone follow-up calls over 12 months. In the assessment clinic, a standardised protocol is followed to identify potential underlying causes for the chronic pain and enable appropriate onward referrals to existing services for targeted and individualised treatment. Outcomes are assessed by questionnaires at 6 and 12 months after randomisation. The co-primary outcomes are pain severity and pain interference assessed using the Brief Pain Inventory at 12 months after randomisation. Secondary outcomes relate to resource use, function, neuropathic pain, mental well-being, use of pain medications, satisfaction with pain relief, pain frequency, capability, health-related quality of life and bodily pain. After trial completion, up to 30 patients in the intervention group will be interviewed about their experiences of the care pathway. Discussion If shown to be clinically and cost-effective, this care pathway intervention could improve the management of chronic pain after total knee replacement. Trial registration ISRCTN registry (ISRCTN92545361), prospectively registered on 30 August 2016. Electronic supplementary material The online version of this article (10.1186/s13063-018-2516-8) contains supplementary material, which is available to authorized users.

Importance Prostate cancer screening remains controversial because potential mortality or quality-of-life benefits may be outweighed by harms from overdetection and overtreatment. Objective To evaluate the effect of a single prostate-specific antigen (PSA) screening intervention and standardized diagnostic pathway on prostate cancer–specific mortality. Design, Setting, and Participants The Cluster Randomized Trial of PSA Testing for Prostate Cancer (CAP) included 419 582 men aged 50 to 69 years and was conducted at 573 primary care practices across the United Kingdom. Randomization and recruitment of the practices occurred between 2001 and 2009; patient follow-up ended on March 31, 2016. Intervention An invitation to attend a PSA testing clinic and receive a single PSA test vs standard (unscreened) practice. Main Outcomes and Measures Primary outcome: prostate cancer–specific mortality at a median follow-up of 10 years. Prespecified secondary outcomes: diagnostic cancer stage and Gleason grade (range, 2-10; higher scores indicate a poorer prognosis) of prostate cancers identified, all-cause mortality, and an instrumental variable analysis estimating the causal effect of attending the PSA screening clinic. Results Among 415 357 randomized men (mean [SD] age, 59.0 [5.6] years), 189 386 in the intervention group and 219 439 in the control group were included in the analysis (n = 408 825; 98%). In the intervention group, 75 707 (40%) attended the PSA testing clinic and 67 313 (36%) underwent PSA testing. Of 64 436 with a valid PSA test result, 6857 (11%) had a PSA level between 3 ng/mL and 19.9 ng/mL, of whom 5850 (85%) had a prostate biopsy. After a median follow-up of 10 years, 549 (0.30 per 1000 person-years) died of prostate cancer in the intervention group vs 647 (0.31 per 1000 person-years) in the control group (rate difference, −0.013 per 1000 person-years [95% CI, −0.047 to 0.022]; rate ratio [RR], 0.96 [95% CI, 0.85 to 1.08]; P = .50). The number diagnosed with prostate cancer was higher in the intervention group (n = 8054; 4.3%) than in the control group (n = 7853; 3.6%) (RR, 1.19 [95% CI, 1.14 to 1.25]; P

The Hospital Episode Statistics (HES) dataset is a source of administrative 'big data' with potential for costing purposes in economic evaluations alongside clinical trials. This study assesses the validity of coverage in the HES outpatient dataset.Men who died of, or with, prostate cancer were selected from a prostate-cancer screening trial (CAP, Cluster randomised triAl of PSA testing for Prostate cancer). Details of visits that took place after 1/4/2003 to hospital outpatient departments for conditions related to prostate cancer were extracted from medical records (MR); these appointments were sought in the HES outpatient dataset based on date. The matching procedure was repeated for periods before and after 1/4/2008, when the HES outpatient dataset was accredited as a national statistic.4922 outpatient appointments were extracted from MR for 370 men. 4088 appointments recorded in MR were identified in the HES outpatient dataset (83.1%; 95% confidence interval [CI] 82.0-84.1). For appointments occurring prior to 1/4/2008, 2195/2755 (79.7%; 95% CI 78.2-81.2) matches were observed, while 1893/2167 (87.4%; 95% CI 86.0-88.9) appointments occurring after 1/4/2008 were identified (p for difference0.001). 215/370 men (58.1%) had at least one appointment in the MR review that was unmatched in HES, 155 men (41.9%) had all their appointments identified, and 20 men (5.4%) had no appointments identified in HES.The HES outpatient dataset appears reasonably valid for research, particularly following accreditation. The dataset may be a suitable alternative to collecting MR data from hospital notes within a trial, although caution should be exercised with data collected prior to accreditation.

Background: Resource-use measurement by patient recall is characterized by inconsistent methods and a lack of validation. A validated standardized resource-use measure could increase data quality, improve comparability between studies and reduce research burden.Aim: To identify a minimum set of core resource-use items that should be included in a standardized adult instrument for UK health economic evaluation from a provider perspective.Methods: Health economists with experience of UK-based economic evaluations were recruited to participate in an electronic Delphi survey. Respondents were asked to rate 60 resource-use items (e.g. medication names) on a scale of 1 to 9 according to the importance of the item in a generic context. Items considered less important according to predefined consensus criteria were dropped and a second survey was developed. In the second round, respondents received the median score and their own score from round 1 for each item alongside summarized comments and were asked to re-rate items. A final project team meeting was held to determine the recommended core set.Results: 45 participants completed round 1. 26 items were considered less important and dropped, 34 items were retained for the second round and no new items were added. 42 respondents completed round 2 (93.3%), and greater consensus was observed. Following the final meeting, a list of 10 core items was selected with further items identified as suitable for ‘bolt-on’ questionnaire modules.Conclusions: The consensus on 10 items considered important in a generic context suggests that a standardized instrument for core resource-use items is feasible.

Resource use measures, including forms, diaries and questionnaires, are ubiquitous in trial-based economic evaluations in the UK. However, there are concerns about the accuracy of how they are described, which limits the transparency of reporting. We developed a simple and structured taxonomy for methods of resource use measurement by examining 94 resource use measures (RUMs) employed within clinical trials, conducting a descriptive synthesis of the extracted data and soliciting wider opinion during a period of consultation. The reporting of RUMs was found to be varied and inconsistent. Our new taxonomy, which considered the views of 20 consultees, requires that RUMs are reported with a description of the following: (i) the source of data (patient; patient proxy, e.g. carer, parent or guardian; observation of contemporary events; medical records; or other databases); (ii) who completes the RUM (patient or their proxy, and researcher or health care professional); (iii) how it is administered (to self [the patient], face to face or telephone); (iv) how it is recorded (form, questionnaire, log or diary); and (v) medium of recording (e.g. paper or electronically). Based on the present analysis, we have developed a taxonomy for RUMs that should result in data collection methods being described more accurately. Copyright © 2014 John Wiley & Sons, Ltd.

For the last decade, stringent monitoring of waiting time performance targets provided English hospitals with incentives to reduce official waiting times for elective surgery. It is less clear whether the total amount of time patients waited in secondary care, from first referral to outpatient clinic until treatment, has also fallen. We used Hospital Episode Statistics inpatient data for patients undergoing total joint replacement during a period of active monitoring of targets (between 2006/7 and 2008/9) and linked it to outpatient data to reconstruct patients' pathway in the 3 years before surgery and provide alternative measurements of waiting times. Our findings suggest that although official waiting times decreased drastically in our study period, total waiting time in secondary care has not declined. Patients with shorter official waits spent a longer time in a ‘work-up’ period prior to inclusion in the official waiting list, and socio-economic inequities persisted in waiting times for joint replacement. We found no evidence that target policies achieved efficiency gains during our study period. Copyright © 2013 John Wiley & Sons, Ltd.

Objective To investigate factors associated with the successful recruitment of general practices to a randomized controlled trial. Study Design and Setting Analysis of accrual of primary care centers to a randomized controlled trial in the UK. Results Those practices promptly agreeing to take part had better target achievement and a higher proportion of white British residents locally. Participating practices had a mean Quality and Outcomes Framework attainment of 92% of the points available, whereas nonparticipating practices achieved 88% (P = 0.009). Participating practices were located in areas with a higher proportion of white British residents (mean 89%), in comparison to nonparticipating practices (mean 84%, P = 0.004). Reasons given by practices to explain nonparticipation were primarily related to internal factors, with 38% of practices approached saying that they could not participate for such reasons. Conclusion There are some small differences between participating practices and nonparticipants in achievement of government targets and in the local ethnic mix. The primary reason given by practices for nonparticipation was workload or time pressures, with over a third of practices reporting being prevented by issues relating to practice organization. It may be that practices with workload or organizational difficulties require additional support to participate in research.

BackgroundPrevious studies of the effect of school-based interventions to improve healthy behaviours have had important limitations.ObjectiveTo investigate the effectiveness of a school-based intervention to increase physical activity, reduce sedentary behaviour and increase fruit and vegetable consumption.DesignCluster randomised controlled trial.SettingSixty English primary schools.ParticipantsChildren in year 4 (aged 8–9 years) at recruitment, year 5 (aged 9–10 years) during the intervention and immediate follow-up and year 6 (aged 10–11 years) during 1 year of follow-up.InterventionActive for Life Year 5 (AFLY5) included teacher training, lesson plans, materials for 16 lessons, parent-interactive homework and written materials for school newsletters and parents.Main outcome measuresPrimary outcome measures included accelerometer-assessed levels of physical activity and sedentary behaviour, and child-reported consumption of fruit and vegetables. Secondary outcome measures included child-reported screen viewing; consumption of snacks, high-fat food and high-energy drinks; body mass index; and waist circumference.ResultsWe recruited 60 schools (2221 children). At the immediate follow-up, no difference was found between children in intervention and control schools for any of the three primary outcomes. The intervention was effective on three of the nine secondary outcomes; children in intervention schools reported spending less time screen viewing at weekends [–21 minutes per day, 95% confidence interval (CI) –37 to –4 minutes per day], eating fewer servings of snacks per day (–0.22, 95% CI –0.38 to –0.05 servings of snacks per day) and drinking fewer servings of high-energy drinks per day (–0.26, 95% CI –0.43 to –0.10 servings of high-energy drinks per day) than the children in control schools. The results remained consistent 1 year later. The intervention increased children’s perception of maternal efforts to limit the time they spent screen viewing and children’s knowledge about healthy physical activity and fruit and vegetable consumption, with these two mediators explaining approximately one-quarter of the effect of the intervention on screen viewing. The intervention did not affect other mediators. The cost of implementing the intervention from a provider perspective was approximately £18 per child. Process evaluation showed that AFLY5 was implemented with a high degree of fidelity. Teachers supported the aims of AFLY5, but their views of the programme itself were mixed.LimitationsResponses to parental questionnaires for the economic evaluation were low and we struggled to engage all teachers for the process evaluation. Although the participating schools included a range of levels of socioeconomic deprivation, class sizes and rural and urban settings, we cannot assume that results generalise to all primary schools.ConclusionsAFLY5 is not effective at increasing levels of physical activity, reducing sedentary behaviour and increasing fruit and vegetable consumption in primary school children, but may be effective in reducing time spent screen viewing at weekends and the consumption of snacks and high-energy drinks.Future workOur findings suggest that school-based interventions are unlikely to have a major impact on promoting healthy levels of physical activity and healthy diets in primary school children. We would recommend trials of the effect and cost-effectiveness of more intensive family and community interventions.Trial registrationCurrent Controlled Trials ISRCTN50133740.FundingThis project was funded by the National Institute for Health Research Public Health Research programme and will be published in full inPublic Health Research; Vol. 4, No. 7. See the NIHR Journals Library website for further project information.

Methods 85 patients undergoing joint replacement were randomised to receive or not receive an RUL at hospital discharge. A postal RUQ was then administered to participants at 3-months after surgery. A blinded researcher extracted primary care resource use data in relation to the patient’s joint replacement from GP records from hospital discharge until completion of the 3-month RUQ. Data from both sources were coded into use of resource and number of contacts and two binary variables indicating perfect recall were calculated. For each resource use category, descriptive statistics were calculated by data source and trial arm, and adjusted odds ratios were estimated.

BACKGROUND: Periprosthetic joint infection (PJI) is a serious complication of total knee arthroplasty. Two-stage revision is the most widely used technique and considered as the most effective for treating periprosthetic knee infection. The one-stage revision strategy is an emerging alternative option, however, its performance in comparison to the two-stage strategy is unclear. We therefore sought to ask if there was a difference in re-infection rates and other clinical outcomes when comparing the one-stage to the two-stage revision strategy.OBJECTIVE: Our first objective was to compare re-infection (new and recurrent infections) rates for one- and two-stage revision surgery for periprosthetic knee infection. Our second objective was to compare between the two revision strategies, clinical outcomes as measured by postoperative Knee Society Knee score, Knee Society Function score, Hospital for Special Surgery knee score, WOMAC score, and range of motion.DESIGN: Systematic review and meta-analysis.DATA SOURCES: MEDLINE, EMBASE, Web of Science, Cochrane Library, reference lists of relevant studies to August 2015, and correspondence with investigators.STUDY SELECTION: Longitudinal (prospective or retrospective cohort) studies conducted in generally unselected patients with periprosthetic knee infection treated exclusively by one- or two-stage revision and with re-infection outcomes reported within two years of revision surgery. No clinical trials comparing both revision strategies were identified.REVIEW METHODS: Two independent investigators extracted data and discrepancies were resolved by consensus with a third investigator. Re-infection rates from 10 one-stage studies (423 participants) and 108 two-stage studies (5,129 participants) were meta-analysed using random-effect models after arcsine transformation.RESULTS: The rate (95% confidence intervals) of re-infection was 7.6% (3.4-13.1) in one-stage studies. The corresponding re-infection rate for two-stage revision was 8.8% (7.2-10.6). In subgroup analyses, re-infection rates remained generally similar for several study-level and clinically relevant characteristics. Postoperative clinical outcomes of knee scores and range of motion were similar for both revision strategies.LIMITATIONS: Potential bias owing to the limited number of one-stage revision studies and inability to explore heterogeneity in greater detail.CONCLUSIONS: Available evidence from aggregate published data suggest the one-stage revision strategy may be as effective as the two-stage revision strategy in treating infected knee prostheses in generally unselected patients. Further investigation is warranted.SYSTEMATIC REVIEW REGISTRATION: PROSPERO 2015: CRD42015017327.

To investigate the relationship between iron status in infancy and type of milk and weaning solids consumed.An observational cohort study.928 term infants from the Avon Longitudinal Study of Parents and Children in 1993-94.Haemoglobin and ferritin concentrations at 8 and 12 months were assessed in relation to type and quantity of milk intake at 8 months.By WHO criteria, 22.7% of the infants were anaemic at 8 months and 18.1% at 12 months. More breast--than formula-fed infants were anaemic at 8 and 12 months. Cows' milk as the main drink was associated with increased anaemia at 12 months and low ferritin at 8 and 12 months. No association was found between any nutrients and haemoglobin concentrations. Protein and non-haem iron intakes were positively associated with ferritin concentrations and calcium intake negatively. This effect was more marked in infants being fed cows' milk. More than 25% of infants in the breast milk and cows' milk groups and 41% of infants having6 breast feeds per day had iron intakes below the lower reference nutrient intake. Feeding cows' milk or formula above 600 ml or6 breast feeds per day was associated with lower intakes of solids.Both breast and cows' milk feeding were associated with higher levels of anaemia. Satisfactory iron intake from solids in later infancy is more likely if formula intake is600 ml per day and breast feeds are limited to6 feeds per day. Cows' milk should be strongly discouraged as a main drink before 12 months.

UNLABELLED This study examines whether planning to be employed postpartum has an effect on initiation of breastfeeding. Data were collected from questionnaires completed by mothers who were subjects in the prospective, population-based, Avon Longitudinal Study of Pregnancy and Childhood. The mothers of 10,530 full-term singleton infants gave information during pregnancy on their postpartum employment plans and their initial infant feeding methods. Information was also given by 7642 of these mothers on the timing of their postpartum employment plans. Adjusted logistic regression was performed to identify associations between (a) "any" plans to work postpartum and the initiation of breastfeeding, and (b) the timing of the commencement of work postpartum, and the initiation of breastfeeding. A total of 8316 (79%) of the women initiated breastfeeding. The decision to breastfeed was not associated with "any" plans to work postpartum. However, women who planned to commence work prior to 6 wk postpartum were significantly less likely to initiate breastfeeding compared with those not intending to work postpartum. Older, more highly educated women, women who had or were planning to attend childbirth classes, women who were breastfed as infants, women who did not smoke and women who were giving birth to their first child were significantly more likely to initiate breastfeeding. CONCLUSION Planning to return to employment prior to 6 wk postpartum reduces the likelihood of initiating breastfeeding. As increasing numbers of mothers are returning to work shortly after the birth of their child, this finding could have implications for maintaining the current level of breastfeeding.

Background The Arthroplasty Pain Experience (APEX) studies are two randomised controlled trials in primary total hip (THR) and total knee replacement (TKR) at a large UK orthopaedics centre. APEX investigated the effect of local anaesthetic wound infiltration (LAI), administered before wound closure, in addition to standard analgesia, on pain severity at 12 months. This article reports results of the within-trial economic evaluations. Methods Cost-effectiveness was assessed from the health and social care payer perspective in relation to quality adjusted life years (QALYs) and the primary clinical outcome, the WOMAC Pain score at 12-months follow-up. Resource use was collected from hospital records and patient-completed postal questionnaires, and valued using unit cost estimates from local NHS Trust finance department and national tariffs. Missing data were addressed using multiple imputation chained equations. Costs and outcomes were compared per trial arm and plotted in cost-effectiveness planes. If no arm was dominant (i.e., more effective and less expensive than the other), incremental cost-effectiveness ratios were estimated. The economic results were bootstrapped incremental net monetary benefit statistics (INMB) and cost-effectiveness acceptability curves. One-way deterministic sensitivity analyses explored any methodological uncertainty. Results In both the THR and TKR trials, LAI was the dominant treatment: cost-saving and more effective than standard care, in relation to QALYs and WOMAC Pain. Using the £20,000 per QALY threshold, in THR, the INMB was £1,125 (95 % BCI, £183 to £2,067) and the probability of being cost-effective was over 98 %. In TKR, the INMB was £264 (95 % BCI, −£710 to £1,238), but there was only 62 % probability of being cost-effective. When considering an NHS perspective only, LAI was no longer dominant in THR, but still highly cost-effective, with an INMB of £961 (95 % BCI, £50 to £1,873). Conclusions Administering LAI is a cost-effective treatment option in THR and TKR surgeries. The evidence, because of larger QALY gain, is stronger for THR. In TKR, there is more uncertainty around the economic result, and smaller QALY gains. Results, however, point to LAI being cheaper than standard analgesia, which includes a femoral nerve block. Trial registration ISRCTN96095682, 29/04/2010. Electronic supplementary material The online version of this article (doi:10.1186/s12916-015-0389-1) contains supplementary material, which is available to authorized users.

Supplemental Digital Content is Available in the Text. Intraoperative local anaesthetic infiltration can reduce chronic postsurgical pain at 1 year after total hip replacement., Total hip replacement (THR) and total knee replacement (TKR) are usually effective at relieving pain; however, 7% to 23% of patients experience chronic postsurgical pain. These trials aimed to investigate the effect of local anaesthetic wound infiltration on pain severity at 12 months after primary THR or TKR for osteoarthritis. Between November 2009 and February 2012, 322 patients listed for THR and 316 listed for TKR were recruited into a single-centre double-blind randomised controlled trial. Participants were randomly assigned (1:1) to receive local anaesthetic infiltration and standard care or standard care alone. Participants and outcomes assessors were masked to group allocation. The primary outcome was pain severity on the WOMAC Pain Scale at 12 months after surgery. Analyses were conducted using intention-to-treat and per-protocol approaches. In the hip trial, patients in the intervention group had significantly less pain at 12 months postoperative than patients in the standard care group (differences in means: 4.74; 95% confidence interval [CI]: 0.95-8.54; P = 0.015), although the difference was not clinically significant. Post hoc analysis found that patients in the intervention group were more likely to have none to moderate pain than severe pain at 12 months than those in the standard care group (odds ratio: 10.19; 95% CI: 2.10-49.55; P = 0.004). In the knee trial, there was no strong evidence that the intervention influenced pain severity at 12 months postoperative (difference in means: 3.83; 95% CI: −0.83 to 8.49; P = 0.107). In conclusion, routine use of infiltration could be beneficial in improving long-term pain relief for some patients after THR.

OBJECTIVE. Rapid infant weight gain has been shown to predict later obesity risk; however, it is unclear which factors influence infant diet and weight gain. The objective of this study was to determine whether different feeding patterns and energy intakes that are provided to infants affect body weight and BMI later in childhood. METHODS. This representative birth cohort study was conducted in the United Kingdom. Energy intake at age 4 months was estimated from 1-day unweighed dietary records in 881 infants and related to their childhood weight gain and BMI. RESULTS. Among formula- or mixed-fed infants (N = 582), energy intake was higher in first-born infants (mean ± SE: 2730 ± 29.4 kJ/day; n = 263) than in subsequent-born infants (2620.8 ± 25.2 kJ/day; n = 296). Energy intake at 4 months was also higher in infants who were given solid foods earlier (1–2 months: 2805.6 ± 50.4 kJ/day, n = 89; 2–3 months: 2658.6 ± 25.2 kJ/day, n = 339; 4+ months: 2587.2 ± 46.2 kJ/day, n = 111). Higher energy intake at 4 months predicted greater weight gain between birth to age 1, 2, or 3 years and larger body weight and BMI at ages 1 to 5 years. No significant associations were seen in breastfed infants (N = 299). CONCLUSIONS. Among formula- or mixed-fed infants, dietary energy intake at age 4 months predicted postnatal weight gain and childhood obesity risk. Both prenatal and postnatal factors may influence infant energy intake and postnatal weight gain.

Objective To determine the impact of a community based Helicobacter pylori screening and eradication programme on the incidence of dyspepsia, resource use, and quality of life, including a cost consequences analysis. Design H pylori screening programme followed by randomised placebo controlled trial of eradication. Setting Seven general practices in southwest England. Participants 10 537 unselected people aged 20-59 years were screened for H pylori infection ( 13 C urea breath test); 1558 of the 1636 participants who tested positive were randomised to H pylori eradication treatment or placebo, and 1539 (99%) were followed up for two years. Intervention Ranitidine bismuth citrate 400 mg and clarithromycin 500 mg twice daily for two weeks or placebo. Main outcome measures Primary care consultation rates for dyspepsia (defined as epigastric pain) two years after randomisation, with secondary outcomes of dyspepsia symptoms, resource use, NHS costs, and quality of life. Results In the eradication group, 35% fewer participants consulted for dyspepsia over two years compared with the placebo group (55/787 v 78/771; odds ratio 0.65, 95% confidence interval 0.46 to 0.94; P = 0.021; number needed to treat 30) and 29% fewer participants had regular symptoms (odds ratio 0.71, 0.56 to 0.90; P = 0.05). NHS costs were £84.70 (£74.90 to £93.91) greater per participant in the eradication group over two years, of which £83.40 ($146; €121) was the cost of eradication treatment. No difference in quality of life existed between the two groups. Conclusions Community screening and eradication of H pylori is feasible in the general population and led to significant reductions in the number of people who consulted for dyspepsia and had symptoms two years after treatment. These benefits have to be balanced against the costs of eradication treatment, so a targeted eradication strategy in dyspeptic patients may be preferable.

A cost-consequences analysis of minor injuries telemedicine was performed alongside a randomized controlled trial in a UK peripheral emergency department. The main outcome measures were safety and clinical effectiveness at seven days after presentation. Costs to the National Health Service (NHS) and patients and their families, for 253 patients, were estimated for seven days following randomization. The mean cost to the NHS for the telemedicine patients was £78.61 and for those assessed routinely was £39.15. For costs incurred by patients and their families the respective figures were £58.24 and £43.95. Sensitivity analysis showed the initial results to be robust. Telemedicine was a more expensive option for providing minor injuries care in a general-practitioner-supported peripheral emergency department, while consequences did not vary greatly between the different options.

Background and Objective: Recruitment to randomized trials is often difficult, but few studies have investigated interventions to improve recruitment. In a randomized trial nested within a trial of treatments for localized prostate cancer, we investigated the comparative effectiveness and cost-effectiveness of nurses and surgeons in recruiting patients. Methods: Men with localized prostate cancer were randomized to see a nurse or urologic surgeon for an “information appointment” in which they were asked to consent to the ProtecT treatment trial comparing surgery, radiotherapy, and active monitoring. Analysis was conducted by intention to treat using chi-square with 95% confidence intervals for proportions and differences between groups. An economic evaluation was performed using the duration of appointments and grade of recruitment staff. Results: Case-finding identified 167 men with localized prostate cancer. One hundred fifty (90%) took part in the recruitment trial. There was a 4.0% difference between nurses and surgeons in recruitment rates (67% nurses, 71% urologists, 95% CI −10.8% to +18.8%, P = .60). Cost-minimization analysis showed that nurses spent longer times with patients but surgeon costs were higher and nurses often supported surgeon-led clinics. Conclusion: Nurses were as effective and more cost-effective recruiters than urologic surgeons. This suggests an increased role for nurses in recruiting patients to randomized trials.

Economic evaluation is a key contributor to decision making in health care, and it is important that it is carried out as effectively and reliably as possible. Studies carried out alongside randomised controlled trials are required to contribute real-world evidence to the decision-making process. However, the requirement that resource use be measured as well as effectiveness data within a trial results in additional complexity for trialists, and there are a number of methodological areas in which improvement is needed. This article reviews the literature in methodological work carried out to inform economic evaluation studies conducted alongside randomised controlled trials. Recent advances in areas including overall trial design, measuring resource use, measuring outcomes and reporting economic evaluations are discussed.

s / Osteoarthritis and Cartilage 22 (2014) S7–S56 S9 cartilage and open a new window of opportunity to modulate the Wnt pathway for the treatment of acute and chronic cartilage injury. 5 THE EFFECT OF LOCAL ANAESTHETIC WOUND INFILTRATION ON CHRONIC PAIN AFTER TOTAL HIP REPLACEMENT: A RANDOMISED CONTROLLED TRIAL V. Wylde y, E. Lenguerrand y, R. Gooberman-Hill y, A. Beswick y, E. Marques y, S. Noble y, J. Horwood y, M. Pyke z, P. Dieppe x, A. Blom y. yUniv. of Bristol, Bristol, United Kingdom; zNorth Bristol NHS Trust, Bristol, United Kingdom; xUniv. of Exeter, Exeter, United Kingdom Purpose: Most patients who have hip replacement do so to relieve pain and stiffness associated with osteoarthritis. However, around 10% of patients who have total hip replacement report chronic pain related to their operated joint 3 months after surgery. It is important to identify ways to reduce the chance that patients will have this type of ongoing pain. A known risk factor for chronic post-surgical pain is the severity of acute post-operative pain. There is evidence that local anaesthetic wound infiltration reduces acute post-operative pain; however, it is uncertain whether it is also effective at reducing chronic pain in the long-term. The aim of this randomised controlled trial (RCT) was to determine if local anaesthetic wound infiltration could significantly reduce the severity of joint pain at 12-months after total hip replacement. Methods: This study was a double-blind randomised controlled trial of patients undergoing primary total hip replacement for osteoarthritis at a high volume elective orthopaedic centre in the UK. Patients were randomised to receive additional intra-operative local anaesthetic wound infiltration or the standard anaesthesia regimen alone. The usual anaesthesia regimen consisted of spinal or general anaesthetic, depending on patient clinical factors. Patients in the intervention group received an added injection of 60 mls of 0.25% bupivacaine with 1 in 200,000 adrenaline at the wound site before surgical closure. Postoperative pain management was the same for the intervention and usual care group, and included a patient-controlled analgesia device. Randomisation was minimised by baseline hip pain severity and surgical approach. The primary outcome was pain at 12-months postoperative measured by the WOMAC Pain scale. Secondary outcomes included the WOMAC Function and Stiffness scales, the Intermittent and Constant Osteoarthritis Pain (ICOAP) measure and the PainDETECT (a measure of neuropathic pain), collected by postal questionnaires administered at 3-months, 6-months and 12-months after surgery. Measurements of daily acute post-operative pain severity were collected on post-operative days 1-3 using a visual analogue scale. Complications and adverse events were collected from patients’ self-report at 3-months and 12-months and a review of medical records. WOMAC Pain scores at 12-months post-operative were categorised into “No pain”; “Mild”; “Moderate” and “Severe” and analyzed using generalized ordered logit models in an intent-to-treat approach. Results are presented as odds ratios and 95% confidence intervals (CIs). Secondary outcomes were analysed using generalised linear models and generalized linear mixed models. Results: 639 eligible patients were approached to take part in this study and 322 consented to participate (50% recruitment rate). Prior to surgery, 163 patients were randomised to the intervention group and 159 to the standard care group. Patients receiving additional local anaesthetic wound infiltration were less likely to report severe pain at 12months post-operative compared with patients receiving the usual anaesthetic regimen alone (OR1⁄40.13; 95% CIs1⁄40.03, 0.62; p1⁄40.011). At 12-months post-operative, patients in the intervention group were also less likely to report neuropathic pain on the PainDETECT questionnaire (OR1⁄40.22; 95% CIs1⁄40.05, 0.97; p1⁄40.046). No differences were observed for outcomes assessed through ICOAP, WOMAC function or WOMAC stiffness questionnaires. During their inpatient stay, patients of both groups reported comparable levels of daily pain, with the exception of pain on the second post-operative night (Coef.1⁄4 -0.83; 95% CIs -1.41, -0.26; p1⁄40.005). Complications and adverse events were similar between the intervention and standard care groups. Conclusions: This is the first RCT to assess the longer-term effects of a local anaesthetic wound infiltration on pain severity after hip replacement. We found that local anaesthetic wound infiltration administered before wound closure is effective in reducing the number of patients experiencing severe pain at 12-months after hip replacement. There was also some evidence of reductions in neuropathic pain at 12-months post-operative and pain on the second post-operative night for patients in the intervention group compared with the usual care group. We recommend the addition of local anaesthetic wound infiltration to the usual anaesthesia regimen during primary total hip replacement surgery to reduce the risk of severe chronic pain after surgery. 6 EFFECTIVENESS OF EXERCISE THERAPY ADDED TO GENERAL PRACTITIONERS’ CARE VERSUS GENERAL PRACTITIONERS’ CARE ALONE IN PATIENTS WITH HIP OSTEOARTHRITIS C. Teirlinck y, P. Luijsterburg y, J. Dekker z, A. Bohnen y, P. van Es y, J. Verhaar y, M. Koopmanschap x, B. Koes y, S. Bierma-Zeinstra y. y Erasmus MC, Erasmus Univ. Med. Ctr., Rotterdam, Netherlands; zVU Med. Ctr./EMGO Inst., Amsterdam, Netherlands; x Erasmus Univ. Rotterdam, Rotterdam, Netherlands Purpose: The main goal of this comparative study was to investigate whether exercise therapy added to general practitioners’ care is effective compared to general practitioners’ care only in patients with a new episode of hip OA in general practice, over a period of 12 months. Methods: Study design used was a randomized controlled trial with a parallel group design. Patients could participate the trial if they were 45 years or older, comply with the clinical American College of Rheumatology criteria for hip OA, and visited their general practitioner for a new episode of complaints due to hip osteoarthritis. Patients were excluded if they: 1) were already treated with exercise therapy in the present episode of hip OA, 2) had a hip pain score of

Aim To investigate the variations in sociodemographic characteristics of mothers in relation to the types of milk and supplementary drinks consumed by their infants at 4 and 8 months of age. Study design The carers of a randomly chosen population sample of over 1000 infants from the Avon Longitudinal Study of Pregnancy and Childhood (ALSPAC) were asked to record all foods and drinks consumed by the child in a 24-h period at both 4 and 8 months of age. Self-completion postal questionnaires were used to ascertain sociodemographic characteristics of the mothers and their infants. Methods Significant differences in the types of milks and supplementary drinks consumed within sociodemographic groups were identified. Infants were also grouped according to the types of milks they were receiving at each age and further differences in sociodemographic characteristics were investigated. Results Highly significant differences existed among various sociodemographic characteristics with regard to the types of drinks used at both ages. Maternal educational level was the most influential of the sociodemographic variables in explaining the differences in consumption of all types of drinks given at 4 months, in particular for breast milk use. Maternal age was also significantly associated with breast feeding. The use of fruit drinks was significantly associated with the presence of older siblings in the family and the use of herbal drinks with the duration of breast feeding. At 8 months of age maternal educational level was again the most highly associated of the sociodemographic variables, being significantly associated with the use of most of the drinks. The presence of older siblings also had a significant independent effect as did duration of breast feeding. The feeding of cows’ (or animal) milk as a main drink at 8 months, contrary to recommendation, was most likely in the group of mothers with vocational education, those in council accommodation, those with two or more children and those with difficulty affording food. Conclusion We have identified certain characteristics of mothers who were more likely than others not to follow current recommendations on infant feeding. The educational level of mothers appears to be of major significance in the choices made about the types of drinks given to infants. It may be possible to target information about infant feeding to certain groups of mothers thus improving weaning patterns.

Background Low levels of physical activity, high levels of sedentary behaviour and low levels of fruit and vegetable consumption are common in children and are associated with adverse health outcomes. The aim of this paper is to describe the protocol for a cluster randomised controlled trial (RCT) designed to evaluate a school-based intervention that aims to increase levels of physical activity, decrease sedentary behaviour and increase consumption of fruit and vegetables in school children. Methods/design The Active for Life Year 5 (AFLY5) study is a school-based, cluster RCT that targets school children in Year 5 (age 9-10 years). All state junior/primary schools in the area covered by Bristol City and North Somerset Council are invited to participate; special schools are excluded. Eligible schools are randomised to one of two arms: intervention arm (receive the intervention 2011-2012) and control arm (receive the intervention after the final follow-up assessment, 2013-2014). The primary outcomes of the trial are levels of accelerometer assessed physical activity and sedentary behaviour and questionnaire assessed fruit and vegetable consumption. A number of secondary outcomes will also be measured, including body mass index, waist circumference and overweight/obesity. Outcomes will be assessed at baseline (prior to intervention when the children are in Year 4), at the end of intervention 'immediate follow-up' and '12 months long-term' follow-up. We will use random effects linear and logistic regression models to compare outcomes by randomised arm. The economic evaluation from a societal perspective will take the form of a cost consequence analysis. Data from focus groups and interviews with pupils, parents and teachers will be used to increase understanding of how the intervention has any effect and is integrated into normal school activity. Discussion The results of the trial will provide information about the public health effectiveness of a school-based intervention aimed at improving levels of physical activity, sedentary behaviour and diet in children. Trial registration ISRCTN50133740

Background Health economists frequently rely on methods based on patient recall to estimate resource utilization. Access to questionnaires and diaries, however, is often limited. This study examined the feasibility of establishing an open-access Database of Instruments for Resource-Use Measurement, identified relevant fields for data extraction, and outlined its design. Methods An electronic survey was sent to authors of full UK economic evaluations listed in the National Health Service Economic Evaluation Database (2008–2010), authors of monographs of Health Technology Assessments (1998–2010), and subscribers to the JISCMail health economics e-mailing list. The survey included questions on piloting, validation, recall period, and data capture method. Responses were analyzed and data extracted to generate relevant fields for the database. Results A total of 143 responses to the survey provided data on 54 resource-use instruments for inclusion in the database. All were reliant on patient or carer recall, and a majority (47) were questionnaires. Thirty-seven were designed for self-completion by the patient, carer, or guardian, and the remainder were designed for completion by researchers or health care professionals while interviewing patients. Methods of development were diverse, particularly in areas such as the planning of resource itemization (evident in 25 instruments), piloting (25), and validation (29). Conclusion On the basis of the present analysis, we developed a Web-enabled Database of Instruments for Resource-Use Measurement, accessible via www.DIRUM.org. This database may serve as a practical resource for health economists, as well as a means to facilitate further research in the area of resource-use data collection.

Background For the majority of patients with osteoarthritis (OA), joint replacement is a successful intervention for relieving chronic joint pain. However, between 10-30% of patients continue to experience chronic pain after joint replacement. Evidence suggests that a risk factor for chronic pain after joint replacement is the severity of acute post-operative pain. The aim of this randomised controlled trial (RCT) is to determine if intra-operative local anaesthethic wound infiltration additional to a standard anaethesia regimen can reduce the severity of joint pain at 12-months after total knee replacement (TKR) and total hip replacement (THR) for OA. Methods 300 TKR patients and 300 THR patients are being recruited into this single-centre double-blind RCT. Participants are recruited before surgery and randomised to either the standard care group or the intervention group. Participants and outcome assessors are blind to treatment allocation throughout the study. The intervention consists of an intra-operative local anaesthetic wound infiltration, consisting of 60 mls of 0.25% bupivacaine with 1 in 200,000 adrenaline. Participants are assessed on the first 5 days post-operative, and then at 3-months, 6-months and 12-months. The primary outcome is the WOMAC Pain Scale, a validated measure of joint pain at 12-months. Secondary outcomes include pain severity during the in-patient stay, post-operative nausea and vomiting, satisfaction with pain relief, length of hospital stay, joint pain and disability, pain sensitivity, complications and cost-effectiveness. A nested qualitative study within the RCT will examine the acceptability and feasibility of the intervention for both patients and healthcare professionals. Discussion Large-scale RCTs assessing the effectiveness of a surgical intervention are uncommon, particulary in orthopaedics. The results from this trial will inform evidence-based recommendations for both short-term and long-term pain management after lower limb joint replacement. If a local anaesthetic wound infiltration is found to be an effective and cost-effective intervention, implementation into clinical practice could improve long-term pain outcomes for patients undergoing lower limb joint replacement. Trial registration Current Controlled Trials ISRCTN96095682

Background Depression is common and can have devastating effects on the life of adolescents. Psychological interventions are the first-line for treating or preventing depression among adolescents. This proposal aims to evaluate a school-based, universal psychological intervention to reduce depressive symptoms among student's aged 13-14 attending municipal state secondary schools in Santiago, Chile. Study design This is a cluster randomised controlled trial with schools as the main clusters. We compared this intervention with a control group in a study involving 22 schools, 66 classes and approximately 2,600 students. Students in the active schools attended 11 weekly and 3 booster sessions of an intervention based on cognitive-behavioural models. The control schools received their usual but enhanced counselling sessions currently included in their curriculum. Mean depression scores and indicators of levels of functioning were assessed at 3 and 12 months after the completion of the intervention in order to assess the effectiveness of the intervention. Direct and indirect costs were measured in both groups to assess the cost-effectiveness of this intervention. Discussion As far as we are aware this is the first cluster randomised controlled trial of a school intervention for depression among adolescents outside the Western world. Trial Registration ISRCTN19466209

SUMMARY Randomised controlled trial (RCT)-based cost-effectiveness analyses, which are prone to missing data, are increasingly used in healthcare technology assessment. This has highlighted the need for appropriate methodological approaches to the handling of missing data. This paper reviews missing data methodology used in RCT-based cost-effectiveness analyses since 2003. Complete case analysis, which may lead to inappropriate conclusions, is still the most popular approach and its use has increased with time. The degree of missing data in cost-effectiveness analyses was often poorly reported and the methodology was often unclear. Reporting of missing data sensitivity analyses would improve article transparency. Copyright © 2010 John Wiley & Sons, Ltd.

Objective: To evaluate the effectiveness and cost of obtaining consent for review of medical records within the passively observed non-intervention arm of a cluster randomized controlled trial, ‘Comparison Arm for ProtecT’. Methods: Two hundred and thirty men, who had been notified to the trial by cancer registries as having prostate cancer, were sent a consent form from their general practitioner or secondary care clinician. The consent rate of participants to the review of their medical records and the estimated costs of the process were evaluated. Results: One hundred and seventy-nine men (84%: 95% CI = 78%, 89%) consented to have their medical notes reviewed at an estimated cost of £123 (€172, $248) per person. Conclusions: A high consent rate for review of medical notes is achievable but at a cost. There needs to be renewed debate about the automatic need for consent to review medical records where the chance of personal harm is negligible and the purpose of the review is to provide robust evidence to save lives, prevent needless suffering, and improve the effectiveness and efficiency of health care delivery.

Background Missing cost and outcomes data is a common problem for health economists analysing RCTs. Systematic reviews of the economic evaluation literature suggest that many analysts use crude methods (e.g. complete case analysis or single imputation) which are vulnerable to bias and may underestimate uncertainty. Multiple imputation (MI) is more appropriate if data are missing at random, but raises a number of methodological and practical challenges. Two case study RCTs assessing the costeffectiveness of new interventions are used to explore these challenges.