Search

Abstract Background The aim of the study was to estimate the long-term cost-effectiveness of the Support and Treatment After Replacement (STAR) care pathway for chronic pain after total knee replacement compared with usual postoperative care. Methods Study design: A decision-analytic (cohort Markov) model was used for the simulation with time dependent annual transition probabilities and a time horizon of five years. Setting: Patients treated by National Health Service (NHS) hospitals in England and Wales. Study population: Adults classified as having chronic pain three months after undergoing a total knee replacement. Intervention: The STAR care pathway following a total knee replacement. Comparator: Usual postoperative care following a total knee replacement. Perspective: The study was undertaken from the perspective of the NHS. Outcome measures: Quality-adjusted life years and healthcare costs. Discounting: A rate of 3.5% for both costs and health utility. Results Model results indicate that the STAR intervention would dominate current practice by providing a gain in quality-adjusted life years (QALYs) of 0.086 and a reduction of £375 (per person) in costs over the first five years. The incremental net monetary benefit of the STAR intervention was estimated at £2,086 (at a threshold of £20,000 per QALY). Probabilistic sensitivity analysis suggests the STAR intervention is likely to be cost-effective with a probability of 0.62. The results remain robust to changes in model assumptions on comparator utility and the timing of the start of the intervention. If hospital admission costs are assumed not to be reduced by the STAR intervention, it would no longer be cost saving, but it would likely be cost-effective based on probabilistic sensitivity analysis (0.59). Conclusion Evidence from the economic model suggests that the STAR care pathway is likely to be cost-effective and potentially dominant from an NHS perspective. Trial registration The STAR trial is registered with ISRCTN, ISRCTN92545361.

Abstract Background The Support and Treatment After Replacement (STAR) care pathway is a clinically important and cost-effective intervention found to improve pain outcomes over one year for people with chronic pain three months after total knee replacement (TKR). We followed up STAR trial participants to evaluate the longer-term clinical- and cost-effectiveness of this care pathway. Methods Participants who remained enrolled on the trial at one year were contacted by post at a median of four years after randomisation and invited to complete a questionnaire comprising the same outcomes collected during the trial. We captured pain (co-primary outcome using the Brief Pain Inventory (BPI) pain severity and interference scales; scored 0–10, best to worst), function, neuropathic characteristics, emotional aspects of pain, health-related quality of life, and satisfaction. Electronic hospital informatics data on hospital resource use for the period of one to four years post-randomisation were collected from participating hospital sites. The economic evaluation took an National Health Service (NHS) secondary care perspective, with a four-year time horizon. Results Overall, 226/337 (67%) of participants returned completed follow-up questionnaires, yielding adjusted between-group differences in BPI means of -0.42 (95% confidence interval, CI (-1.07, 0.23); p = 0.20) for pain severity and − 0.64 (95% CI -1.41, 0.12); p = 0.10) for pain interference. Analysis using a multiple imputed data set (n = 337) showed an incremental net monetary benefit in favour of the STAR care pathway of £3,525 (95% CI -£990 to £8,039) at a £20,000/QALY willingness-to-pay threshold, leading to a probability that the intervention was cost-effective of 0.94. Conclusions The magnitude of the longer-term benefits of the STAR care pathway are uncertain due to attrition of trial participants; however, there is a suggestion of some degree of sustained clinical benefit at four years. The care pathway remained cost-effective at four years. Trial registration ISRCTN: 92,545,361.

Background Conservative therapies are recommended as initial treatment for male lower urinary tract symptoms. However, there is a lack of evidence on effectiveness and uncertainty regarding approaches to delivery. Objective The objective was to determine whether or not a standardised and manualised care intervention delivered in primary care achieves superior symptomatic outcome for lower urinary tract symptoms to usual care. Design This was a two-arm cluster randomised controlled trial. Setting The trial was set in 30 NHS general practice sites in England. Participants Participants were adult men (aged ≥ 18 years) with bothersome lower urinary tract symptoms. Interventions Sites were randomised 1 : 1 to deliver the TReatIng Urinary symptoms in Men in Primary Health care using non-pharmacological and non-surgical interventions trial intervention or usual care to all participants. The TReatIng Urinary symptoms in Men in Primary Health care using non-pharmacological and non-surgical interventions intervention comprised a standardised advice booklet developed for the trial from the British Association of Urological Surgeons’ patient information sheets, with patient and expert input. Patients were directed to relevant sections by general practice or research nurses/healthcare assistants following urinary symptom assessment, providing the manualised element. The healthcare professional provided follow-up contacts over 12 weeks to support adherence to the intervention. Main outcome measures The primary outcome was the validated patient-reported International Prostate Symptom Score 12 months post consent. Rather than the minimal clinically important difference of 3.0 points for overall International Prostate Symptom Score, the sample size aimed to detect a difference of 2.0 points, owing to the recognised clinical impact of individual symptoms. Results A total of 1077 men consented to the study: 524 in sites randomised to the intervention arm (n = 17) and 553 in sites randomised to the control arm (n = 13). A difference in mean International Prostate Symptom Score at 12 months was found (adjusted mean difference of –1.81 points, 95% confidence interval –2.66 to –0.95 points), with a lower score in the intervention arm, indicating less severe symptoms. Secondary outcomes of patient-reported urinary symptoms, quality of life specific to lower urinary tract symptoms and perception of lower urinary tract symptoms all showed evidence of a difference between the arms favouring the intervention. No difference was seen between the arms in the proportion of urology referrals or adverse events. In qualitative interviews, participants welcomed the intervention, describing positive effects on their symptoms, as well as on their understanding of conservative care and their attitude towards the experience of lower urinary tract symptoms. The interviews highlighted that structured, in-depth self-management is insufficiently embedded within general practitioner consultations. From an NHS perspective, mean costs and quality-adjusted life-years were similar between trial arms. The intervention arm had slightly lower mean costs (adjusted mean difference of –£29.99, 95% confidence interval –£109.84 to £22.63) than the usual-care arm, and a small gain in quality-adjusted life-years (adjusted mean difference of 0.001, 95% confidence interval –0.011 to 0.014). Conclusions The intervention showed a small, sustained benefit for men’s lower urinary tract symptoms and quality of life across a range of outcome measures in a UK primary care setting. Qualitative data showed that men highly valued the intervention. Intervention costs were marginally lower than usual-care costs. Limitations of the study included that trial participants were unmasked, with limited diversity in ethnicity and deprivation level. Additional research is needed to assess the applicability of the intervention for a more ethnically diverse population.. Trial registration This trial is registered as ISRCTN11669964. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 16/90/03) and is published in full in Health Technology Assessment; Vol. 28, No. 13. See the NIHR Funding and Awards website for further award information. Plain language summary Urinary problems among men become more common with age. Nearly one-third of all men aged > 65 years experience some urinary symptoms, which can have a substantial effect on their daily lives. Symptoms include needing to pass urine more often, urgently or during the night, and difficulties in passing urine. Men are usually diagnosed and treated by their general practitioner, and should be offered advice on controlling their symptoms themselves (e.g. lifestyle changes and exercises) before trying tablets or surgery. However, it is not known how helpful such advice is, and how general practices can effectively provide it. Thirty general practices in the West of England and Wessex took part in the study. Practices were split into two groups, with each practice providing either the TReatIng Urinary symptoms in Men in Primary Health care using non-pharmacological and non-surgical interventions care package or the practice’s usual care to all of its patients in the trial. The TReatIng Urinary symptoms in Men in Primary Healthcare using nonpharmacological and non-surgical interventions care package included a booklet of advice to help control urinary symptoms, with a nurse or healthcare assistant directing men to relevant sections according to their symptoms, and providing follow-up contacts. We mainly assessed the benefits of the TReatIng Urinary symptoms in Men in Primary Healthcare using nonpharmacological and non-surgical interventions care package, compared with usual care, by using a questionnaire on urinary symptoms completed by participants. A total of 1077 men with urinary symptoms that bothered them joined the study. The main result was that men reported greater improvement in urinary symptoms with the TRIUMPH care package than with usual care, 12 months after joining the study. We also found that men receiving the TRIUMPH care package had a slight improvement in quality of life and outlook on their urinary symptoms. There was no difference between the two groups in the number of patients referred to hospital for treatment, the type, number and severity of side effects or cost to the NHS. Overall, the TRIUMPH care package was more effective in treating men with urinary symptoms than usual care by their general practice. Scientific summary Background Lower urinary tract symptoms (LUTS) can relate to urinary storage or voiding. Among men, the prevalence and severity of symptoms increase with age, with a substantial impact on quality of life. The majority of men presenting with urinary symptoms are assessed and managed by their general practitioner (GP) in the first instance, with conservative therapies recommended as initial treatment. However, there is a lack of evidence on the effectiveness of conservative therapies, and uncertainty regarding approaches to delivery. Provision in primary care is variable and can be time and resource limited, and GPs require practical resources to enhance patient engagement with such interventions. The TReatIng Urinary symptoms in Men in Primary Health care using non-pharmacological and non-surgical interventions (TRIUMPH) trial aimed to address this need in primary care. Objectives The key aim of this research was to determine whether or not a standardised and manualised care intervention achieves superior symptomatic outcome, compared with usual care, for male LUTS, with a primary outcome of overall International Prostate Symptom Score (IPSS) measured 12 months after consent, in a primary care setting. Secondary objectives were to compare the two trial arms with regard to: disease-specific quality of life symptomatic outcomes cost effectiveness relative harms use of NHS resources overall quality of life and general health acceptability of assessment and provision of care patients’ perception of their LUTS. Design This was a pragmatic two-arm cluster randomised controlled trial randomising general practice sites 1 : 1 between a care pathway based on a standardised and manualised care intervention (intervention arm) and one based on usual care (comparator arm) for men with LUTS. The trial design included an internal pilot recruitment phase of 4 months’ duration, primarily to verify feasibility of recruitment before progression to the main phase of the trial. Setting Thirty general practice sites were recruited within nine Clinical Commissioning Groups across the West of England and Wessex Clinical Research Network (CRN) regions in the UK. Participants were identified and recruited from these sites. Participants General Practice Recruitment The CRNs invited general practices to express an interest in taking part in the study. To achieve a balanced range of practices, the following factors were considered in practice selection: number of potentially eligible patients, on conduct of a preliminary database search patient list size deprivation score (calculated using a general practice’s postcode) preference for method of intervention delivery (by practice staff or trial research nurses) treatment room space available for intervention delivery. Participating sites underwent site initiation training. An internal pilot phase was conducted with eight initial sites over a period of 4 months before the main phase of the trial. Participant recruitment This was a pragmatic trial in adult men who considered themselves to have bothersome LUTS and who had presented to primary care within the preceding 5 years with at least one symptom of LUTS. Only men already known to have LUTS (prevalent cases) were screened for inclusion in the trial. Screening was undertaken once by each site pre randomisation, so men newly presenting with LUTS (incident cases) after site randomisation were not included. Interventions Practices were randomised 1 : 1 to deliver the TRIUMPH intervention or a usual-care pathway. The TRIUMPH intervention comprises a LUTS advice booklet developed for the trial from the British Association of Urological Surgeons’ patient information sheets, with patient and expert input, providing the standardised element. Practices in the intervention arm could choose whether the intervention was delivered by central study research nurses or general practice nurses/healthcare assistants (HCAs), who received a 1-hour training session. Patients were directed to relevant sections by the nurses/HCA following symptom assessment, providing the manualised element. The healthcare professional (HCP) provided follow-up contacts over 12 weeks to encourage adherence. Usual care (the comparator arm for the TRIUMPH trial) in this study requested that sites continue to follow their standard local practice for trial patients in terms of delivery and follow-up. Main outcome measures The primary outcome measure was the patient-reported IPSS at 12 months after consent. Key secondary outcomes included quality of life, patient-reported urinary symptoms, adverse events, referrals to secondary care, patient perception of their LUTS, cost effectiveness, number of GP consultations and a qualitative evaluation of patients’ experiences of the intervention. Patient-reported outcomes were collected by questionnaire at baseline and at 6 and 12 months. Other clinical outcomes and NHS resource use were extracted from primary care electronic medical records a minimum of 1 month after the final participant at each site had completed the 12-month follow-up. Qualitative interviews were conducted throughout the trial. Results The trial was successful in meeting general practice site recruitment targets, and participant recruitment exceeded that anticipated. In total, 1077 men consented to the study: 524 in sites randomised to the intervention arm (n = 17) and 553 in sites randomised to the control arm (n = 13). A total of 887 patients (82%) were included in the primary analysis at 12 months post consent. The treatment groups were broadly balanced on baseline characteristics, but the primary outcome measure (IPSS) was slightly lower in the intervention arm than in the usual-care arm (intervention: 13.62 points; usual care: 14.59 points). The intervention was successfully delivered: 98% of men received their intervention booklet and 90% had all three contacts forming the intervention. The primary outcome analysis found that, although there was a reduction in IPSS between baseline and 12 months in both arms, suggesting improved symptoms, symptom improvement was greater in the intervention arm [–1.81, 95% confidence interval (CI) –2.66 to –0.95]. The difference was smaller than the difference we sought to detect in the sample size calculation of 2 points in overall IPSS, and the minimal clinically important difference of 3 points. The improvement in IPSS, however, was mirrored by improvements in the secondary outcomes of incontinence (measured using the International Consultation on Incontinence Questionnaire-Urinary Incontinence-Short Form), IPSS quality-of-life measures and patients’ perception of their LUTS (measured using the Brief Illness Perception Questionnaire). The primary analysis estimates were robust to ways of accounting for clustering and multiple imputation of missing data. High levels of adherence to intervention delivery meant that per-protocol analyses largely reflected the primary analysis. Although there was no strong evidence that the treatment effect was modified by the nature of LUTS at baseline, by who delivered the intervention or by how contact was delivered in the intervention, a post hoc analysis suggests that the treatment effect may have been stronger in the pre-COVID period. No difference was seen between the arms in the proportion of urology referrals or adverse events. In terms of the health economic analysis, from an NHS perspective, costs and quality-adjusted life-years (QALYs) were similar across both trial arms. Compared with the usual-care arm, the intervention arm had slightly lower mean costs (adjusted mean difference of –£29.99, 95% CI –£109.84 to £22.63) and a small gain in QALYs (adjusted mean difference of 0.001, 95% CI –0.011 to 0.014). Two sensitivity analyses adjusting for missing data reversed this finding, reflecting the similar costs and outcomes between the two arms. Overall, the results of the economic evaluation indicate that the costs should not be seen as a limiting factor for the roll-out of the TRIUMPH intervention. Qualitative interviews indicated that many men in both intervention and usual-care arms lived with distressing LUTS for long periods without seeking help. Men tolerated symptoms they portrayed as mundane and inevitable parts of ageing, unworthy of clinical attention, unless severe enough to warrant often unpalatable medication or surgery. Mostly men were unaware that a range of self-management techniques existed and might offer support. In this context, men in the intervention arm strongly welcomed the guidance offered. Men appreciated the accessibility of the booklet, the targeted self-management techniques offered, the interest in their neglected LUTS, the HCP meeting and follow-up contact. Men in the intervention arm reported not only symptom improvement, but also better understanding and a renewed sense of self-efficacy in relation to their symptom management, and an accompanying erosion of the stigma that entangled notions of age, LUTS and inevitable irredeemable bodily decline. Men reported feeling both better able to take action to redress symptoms and more cheerful about their LUTS (and, more broadly, about ageing). Men in the usual-care arm continued to live with distressing symptoms with resigned tolerance. Interviews with both trial participants and GPs in participating practices indicated that self-management guidance for LUTS is currently insufficiently embedded within primary care consultations. Despite describing their contact with primary care positively, men rarely recalled being offered in-depth, structured self-help guidance; men in the usual-care arm remained unfamiliar with the guidance, despite enduring LUTS. Men tended to visit their GP when symptoms were alarming or severe, which may explain why GP encounters often focused on prostate cancer concerns, or moved quickly to medication, forgoing detailed self-management discussions. Most men, and also some GPs, associated pelvic floor exercises with women’s, but not men’s, LUTS. As a result, interviews provided strong grounds for making the intervention guidance routinely available within primary care, to better meet clinical recommendations promoting conservative care for men with LUTS and to better support men’s knowledge and understanding both of their symptoms and of self-management approaches, and to alleviate distressing and neglected symptoms. The strengths of the trial include recruitment to target and excellent follow-up rates, with a clustered trial design to reduce contamination, resulting in informative and robust conclusions. The primary outcome was also intentionally timed to allow the longer-term benefit of the TRIUMPH intervention to be captured, at 12 months post consent, following a 12-week intervention delivery. Sustained benefit was identified, which can be an issue in the longer-term effectiveness of lifestyle and conservative interventions. The limitations of the trial include the necessity of the trial participants being unmasked. In addition, the trial population had only a small number of non-white men, and included only those who had previously sought help from their GP for their LUTS, so may not apply to all men with LUTS. A potential limitation is that sites recruiting to the usual-care arm would potentially have developed renewed awareness of the condition and the current approaches to management as a result of participating in the study. Potentially, this would decrease the observed differences between randomised groups, given that there was some improvement in the usual-care arm in the primary outcome. Conclusions The TRIUMPH intervention showed a sustained benefit for men’s LUTS and quality of life across a range of outcome measures in a UK primary care setting. Although the effect sizes were small, qualitative data showed that men highly valued the intervention. Intervention costs were marginally lower than usual-care costs. The findings show the potential for a short training process to enable nurses or HCA to assess patients and direct them towards appropriate conservative measures in a standardised information booklet. This delivers improved symptoms at low cost, with minimal adverse events. The potential for the same intervention to achieve symptom improvement in incident patients, or for GPs to screen for LUTS to offer the intervention, should be considered. The implications of outcomes in a more diverse population of men need to be evaluated. Trial registration The trial is registered as ISRCTN11669964. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 16/90/03) and is published in full in Health Technology Assessment; Vol. 28, No. 13. See the NIHR Funding and Awards website for further award information.

Abstract Background In contrast to evidence for interventions supporting victim/survivors of domestic violence and abuse (DVA), the effectiveness of perpetrator programmes for reduction of abuse is uncertain. This study aims to estimate the effectiveness and cost-effectiveness of a perpetrator programme for men. Methods Pragmatic two-group individually randomised controlled trial (RCT) with embedded process and economic evaluation. Five centres in southwest England and South Wales aim to recruit 316 (reduced from original target of 366) male domestic abuse perpetrators. These will be randomised 2:1 to a community-based domestic abuse perpetrator programme (DAPP) or usual care comparator with 12-month follow-up. Female partners/ex-partners will be invited to join the study. The intervention for men comprises 23 weekly sessions of a group programme delivered in voluntary sector domestic abuse services. The intervention for female partners/ex-partners is one-to-one support from a safety worker. Men allocated to usual care receive no intervention; however, they are free to access other services. Their partners/ex-partners will be signposted to support services. Data is collected at baseline, and 4, 8 and 12 months’ follow-up. The primary outcome is men’s self-reported abusive behaviour measured by the Abusive Behaviour Inventory (ABI-29) at 12 months. Secondary measures include physical and mental health status and resource use alongside the abuse measure ABI (ABI-R) for partners/ex-partners and criminal justice contact for men. A mixed methods process evaluation and qualitative study will explore mechanisms of effectiveness, judge fidelity to the intervention model using interviews and group observations. The economic evaluation, over a 1-year time horizon from three perspectives (health and social care, public sector and society), will employ a cost-consequences framework reporting costs alongside economic outcomes (Quality-Adjusted Life Years derived from EQ-5D-5L, SF-12 and CHU-9D, and ICECAP-A) as well as the primary and other secondary outcomes. Discussion This trial will provide evidence of the (cost)effectiveness of a DAPP. The embedded process evaluation will further insights in the experiences and contexts of participants and their journey through a perpetrator programme, and the study will seek to address the omission in other studies of economic evaluations. Trial registration ISRCTN15804282, April 1, 2019

Abstract Background Bespoke self-report resource-use measures (RUMs) are commonly developed or adapted for each new randomised controlled trial. Consequently, RUMs lack standardisation and validation is rarely conducted. A new generic RUM, ModRUM, has been developed using a rigorous process, including consultation with health economists and patients. ModRUM includes a concise core healthcare module, designed to be included in all trials, and depth-adding questions, which can replace or be added to core questions as needed. Modules covering other sectors are under development. The aim of this study was to test the acceptability, feasibility, and criterion and construct validity of the healthcare module of ModRUM. Methods Patients who had a recent appointment at their GP practice were invited to complete ModRUM (core module or core module with depth questions), a characteristics form and the EQ-5D-5L. Acceptability was assessed via response rates and questionnaire completion time. Feasibility was assessed by reviewing issues observed in participants’ responses and question completion rates. Construct validity was tested via hypothesis testing and known-group analyses, using Wilcoxon rank-sum and Kruskal–Wallis tests, and a generalised linear model. Criterion validity was tested by comparing ModRUM results with primary care medical records. Sensitivity, specificity, and agreement using Lin’s concordance correlation coefficient (pc) were estimated. Results One hundred patients participated from five GP practices in the South-West of England. Acceptability was higher for the core module (20% versus 10% response rate). Question completion rates were high across both versions (> 90%). Some support was observed for construct validity, with results suggesting that healthcare costs differ dependent on the number of long-term conditions (p 0.83), while specificity varied (0.33–0.88). There was a good level of agreement for GP contacts and costs, and prescribed medication costs (pc > 0.6). Conclusion This study provided preliminary evidence of the acceptability, feasibility, and criterion and construct validity of ModRUM. Further testing is required within trials and with groups that were less well represented in this study.

Objectives To estimate the cost-effectiveness of a primary care intervention for male lower urinary tract symptoms (LUTS) compared with usual care.Design Economic evaluation alongside a cluster randomised controlled trial from a UK National Health Service (NHS) perspective with a 12-month time horizon.Setting Thirty NHS general practice sites in England.Participants 1077 men aged 18 or older identified in primary care with bothersome LUTS.Interventions A standardised and manualised intervention for the treatment of bothersome LUTS was compared with usual care. The intervention group (n=524) received a standardised information booklet with guidance on conservative treatment for LUTS, urinary symptom assessment and follow-up contacts for 12 weeks. The usual care group (n=553) followed local guidelines between general practice sites.Measures Resource use was obtained from electronic health records, trial staff and participants, and valued using UK reference costs. Quality-adjusted life-years (QALYs) were calculated from the EQ-5D-5L questionnaire. Adjusted mean differences in costs and QALYs and incremental net monetary benefit were estimated.Results 866 of 1077 (80.4%) participants had complete data and were included in the base-case analysis. Over the 12-month follow-up period, intervention and usual care arms had similar mean adjusted costs and QALYs. Mean differences were lower in the intervention arm for adjusted costs −£29.99 (95% CI −£109.84 to £22.63) while higher in the intervention arm for adjusted QALYs 0.001 (95% CI −0.011 to 0.014). The incremental net monetary benefit statistic was £48.01 (95% CI −£225.83 to £321.85) at the National Institute for Health and Care Excellence UK threshold of £20 000 per QALY. The cost-effectiveness acceptability curve showed a 63% probability of the intervention arm being cost-effective at this threshold.Conclusions Costs and QALYs were similar between the two arms at 12 months follow-up. This indicates that the intervention can be implemented in general practice at neutral cost.Trial registration number ISRCTN11669964.

Introduction Hearing loss is a common chronic health condition and adversely affects communication and social function resulting in loneliness, social isolation and depression. We know little about the patient experience of living with hearing loss and their views on the quality of the audiology service. In this study, we will develop and validate the first patient-reported experience measure (PREM) to understand patients’ experiences of living with hearing loss and their healthcare interactions with audiology services.Methods and analysis We will develop the PREM in three phases: (1) development of PREM prototype (items/statements) derived from previous qualitative work and narrative review, (2) cognitive interview testing of the PREM prototype using a ‘think aloud’ technique to examine the acceptability and comprehensibility of the tool and refine accordingly and (3) psychometric testing of the modified PREM with 300 participants to assess the reliability and validity of the tool using Rasch analyses with sequential item reduction. Eligible participants will be young people and adults aged 16 years and over who have hearing loss. Participants will be recruited from three clinical sites located in England (Bath, Bristol) and Scotland (Tayside) and non-clinical settings (eg, lip-reading classes, residential care settings, national charity links, social media).Ethics and dissemination The study was approved by the West of Scotland Research Ethics Service (approval date: 6 May 2022; ref: 22/WS/0057) and the Health Research Authority and Health and Care Research Wales (HCRW) Approval (approval date: 14 June 2022; IRAS project ID: 308816). Findings will be shared with our patient and public involvement groups, academics, audiology communities and services and local commissioners via publications and presentations. The PREM will be made available to clinicians and researchers without charge.

Background: People with severe osteoarthritis, other joint conditions or injury may have joint replacement to reduce pain and disability. In the UK in 2019, over 200,000 hip and knee replacements were performed. About 1 in 100 replacements becomes infected, and most people with infected replacements require further surgery. Objectives: To investigate why some patients are predisposed to joint infections and how this affects patients and the NHS, and to evaluate treatments. Design: Systematic reviews, joint registry analyses, qualitative interviews, a randomised controlled trial, health economic analyses and a discrete choice questionnaire. Setting: Our studies are relevant to the NHS, to the Swedish health system and internationally. Participants: People with prosthetic joint infection after hip or knee replacement and surgeons. Interventions: Revision of hip prosthetic joint infection with a single- or two-stage procedure. Main outcome measures: Long-term patient-reported outcomes and reinfection. Cost-effectiveness of revision strategies over 18 months from two perspectives: health-care provider and Personal Social Services, and societal. Data sources: National Joint Registry; literature databases; published cohort studies; interviews with 67 patients and 35 surgeons; a patient discrete choice questionnaire; and the INFORM (INFection ORthopaedic Management) randomised trial. Review methods: Systematic reviews of studies reporting risk factors, diagnosis, treatment outcomes and cost comparisons. Individual patient data meta-analysis. Results: In registry analyses, about 0.62% and 0.75% of patients with hip and knee replacement, respectively, had joint infection requiring surgery. Rates were four times greater after aseptic revision. The costs of inpatient and day-case admissions in people with hip prosthetic joint infection were about five times higher than those in people with no infection, an additional cost of > £30,000. People described devastating effects of hip and knee prosthetic joint infection and treatment. In the treatment of hip prosthetic joint infection, a two-stage procedure with or without a cement spacer had a greater negative impact on patient well-being than a single- or two-stage procedure with a custom-made articulating spacer. Surgeons described the significant emotional impact of hip and knee prosthetic joint infection and the importance of a supportive multidisciplinary team. In systematic reviews and registry analyses, the risk factors for hip and knee prosthetic joint infection included male sex, diagnoses other than osteoarthritis, high body mass index, poor physical status, diabetes, dementia and liver disease. Evidence linking health-care setting and surgeon experience with prosthetic joint infection was inconsistent. Uncemented fixation, posterior approach and ceramic bearings were associated with lower infection risk after hip replacement. In our systematic review, synovial fluid alpha-defensin and leucocyte esterase showed high diagnostic accuracy for prosthetic joint infection. Systematic reviews and individual patient data meta-analysis showed similar reinfection outcomes in patients with hip or knee prosthetic joint infection treated with single- and two-stage revision. In registry analysis, there was a higher rate of early rerevision after single-stage revision for hip prosthetic joint infection, but, overall, 40% fewer operations are required as part of a single-stage procedure than as part of a two-stage procedure. The treatment of hip or knee prosthetic joint infection with early debridement and implant retention may be effective in > 60% of cases. In the INFORM randomised controlled trial, 140 patients with hip prosthetic joint infection were randomised to single- or two-stage revision. Eighteen months after randomisation, pain, function and stiffness were similar between the randomised groups (p = 0.98), and there were no differences in reinfection rates. Patient outcomes improved earlier in the single-stage than in the two-stage group. Participants randomised to a single-stage procedure had lower costs (mean difference –£10,055, 95% confidence interval –£19,568 to –£542) and higher quality-adjusted life-years (mean difference 0.06, 95% confidence interval –0.07 to 0.18) than those randomised to a two-stage procedure. Single-stage was the more cost-effective option, with an incremental net monetary benefit at a threshold of £20,000 per quality-adjusted life-year of £11,167 (95% confidence interval £638 to £21,696). In a discrete choice questionnaire completed by 57 patients 18 months after surgery to treat hip prosthetic joint infection, the most valued characteristics in decisions about revision were the ability to engage in valued activities and a quick return to normal activity. Limitations: Some research was specific to people with hip prosthetic joint infection. Study populations in meta-analyses and registry analyses may have been selected for joint replacement and specific treatments. The INFORM trial was not powered to study reinfection and was limited to 18 months’ follow-up. The qualitative study subgroups were small. Conclusions: We identified risk factors, diagnostic biomarkers, effective treatments and patient preferences for the treatment of hip and knee prosthetic joint infection. The risk factors include male sex, diagnoses other than osteoarthritis, specific comorbidities and surgical factors. Synovial fluid alpha-defensin and leucocyte esterase showed high diagnostic accuracy. Infection is devastating for patients and surgeons, both of whom describe the need for support during treatment. Debridement and implant retention is effective, particularly if performed early. For infected hip replacements, single- and two-stage revision appear equally efficacious, but single-stage has better early results, is cost-effective at 18-month follow-up and is increasingly used. Patients prefer treatments that allow full functional return within 3–9 months. Future work: For people with infection, develop information, counselling, peer support and care pathways. Develop supportive care and information for patients and health-care professionals to enable the early recognition of infections. Compare alternative and new treatment strategies in hip and knee prosthetic joint infection. Assess diagnostic methods and establish NHS diagnostic criteria. Study registration: The INFORM randomised controlled trial is registered as ISRCTN10956306. All systematic reviews were registered in PROSPERO (as CRD42017069526, CRD42015023485, CRD42018106503, CRD42018114592, CRD42015023704, CRD42017057513, CRD42015016559, CRD42015017327 and CRD42015016664). Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Programme Grants for Applied Research programme and will be published in full in Programme Grants for Applied Research; Vol. 10, No. 10. See the NIHR Journals Library website for further project information.

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