搜索结果：Health technology assessment (Winchester, England)

Ovarian cancer survival is stage-dependent: Stage I patients have 90% 5-year survival versus 15% for stage IV. Over 70% of patients worldwide are diagnosed at advanced stages. Ovarian cancer presents with non-specific symptoms (abdominal bloating, early satiety, discomfort/pain, bowel/urinary changes). Current National Institute for Health and Care Excellence guidelines recommend that symptomatic women presenting to primary care are tested with cancer antigen 125 and ultrasound, then referred to secondary care for further triage if these tests are abnormal. Current standard of care risk prediction model used to triage women in National Health Service secondary care is Risk of Malignancy Index 1 combining cancer antigen 125 and simple ultrasound features, which at 250 threshold has 70% sensitivity and 90% specificity. Newer models offer potential for improved sensitivity, earlier diagnosis and better survival outcomes. To evaluate diagnostic strategies for ovarian cancer in women with non-specific symptoms through systematic review, United Kingdom Collaborative Trial of Ovarian Cancer Screening data set analysis, prospective studies and health economic evaluation comparing Risk of Malignancy Index 1 against newer approaches including Risk of Ovarian Malignancy Algorithm, Ovarian-Adnexal Reporting and Data System and International Ovarian Tumour Analysis models, including International Ovarian Tumour Analysis Assessment of Different NEoplasias in the adneXa. Four concurrent work packages: (1) Cochrane systematic review; (2) United Kingdom Collaborative Trial of Ovarian Cancer Screening data set model development; (3) prospective multicentre diagnostic accuracy study (ROCkeTS) with parallel pre/postmenopausal cohorts; and (4) cost-consequence analysis. Allied analyses investigated psychological impact and cancer outcomes from symptom-triggered pathways. ROCkeTS recruited 2453 women across 23 hospitals (2015-23) with symptoms, raised cancer antigen 125 and/or abnormal imaging. Women completed questionnaires, donated blood and underwent transvaginal ultrasound scored by International Ovarian Tumour Analysis terminology by certified National Health Service sonographers with quality assurance. Reference standard was histology for surgical cases or 12-month wellbeing ascertainment. Primary outcome: primary invasive ovarian cancer versus benign or normal. The Cochrane systematic review (58 studies, 30,121 patients and 9061 ovarian cancer cases) demonstrated that most published diagnostic test accuracy studies failed to differentiate between pre- and postmenopausal women, and all were conducted in high-prevalence settings, limiting applicability to routine practice. In the ROCkeTS prospective study in premenopausal women, in the initial cohort recruited prior to protocol change (n = 857), Risk of Malignancy Index 1 at threshold 250 showed poor sensitivity (42.6%, 95% confidence interval 28.3 to 57.8) but high specificity (96.5%, 95% confidence interval 94.7 to 97.8). All other tests improved sensitivity but dropped specificity. International Ovarian Tumour Analysis Assessment of Different NEoplasias in the adneXa at 10% threshold achieved significantly higher sensitivity (89.1%, 95% confidence interval 76.4 to 96.4), higher than all other tests with acceptable specificity (73.2%, 95% confidence interval 69.9 to 76.4). In the ROCkeTS prospective cohort study in postmenopausal women (n = 1242), Risk of Malignancy Index 1 at 250 demonstrated better performance (82.9%, 95% confidence interval 76.7 to 88.0), but International Ovarian Tumour Analysis Assessment of Different NEoplasias in the adneXa at 10% had the best sensitivity at 96.1% (95% confidence interval 92.2 to 98.4) compared to Risk of Malignancy Index 1 with the least drop of specificity. Risk of Ovarian Malignancy Algorithm at manufacturer recommended threshold and Ovarian-Adnexal Reporting and Data System did not improve on Risk of Malignancy Index 1 sensitivity in postmenopausal women. Cancer prevalence differed between premenopausal (5.7%) and postmenopausal (17%) cohorts. Early-stage cancer (I/II) were diagnosed in 60.2% of premenopausal and 41% of postmenopausal cohorts. Cancer diagnosis rates were very low (1.6%) in women under 40 years. High anxiety and distress were noted, particularly in younger women. One in four women with high-grade serous ovarian cancers were diagnosed at early stage (I/II). Complete cytoreduction was achieved in 61.3% of cases, with optimal cytoreduction (≤ 1 cm residual disease) in an additional 15.1%. Cost-consequence analysis demonstrated that a two-step strategy deployed at the same ultrasound sitting, initially triaging out benign looking tumours on ultrasound, then calculating ovarian cancer risk with International Ovarian Tumour Analysis Assessment of Different NEoplasias in the adneXa ultrasound model at 10% demonstrated the best balance across cost, diagnostic yield and cancer deaths compared to other diagnostic strategies. Cohort study required key changes to protocol and post-pandemic recruitment was slow. International Ovarian Tumour Analysis Assessment of Different NEoplasias in the adneXa ultrasound at 10% threshold, delivered by trained National Health Service sonographers demonstrated superior diagnostic performance compared to Risk of Malignancy Index 1 and should be considered as new standard of care for suspected ovarian cancer in pre- and postmenopausal women. A two-step strategy using International Ovarian Tumour Analysis Assessment of Different NEoplasias in the adneXa offers optimal balance across cost, diagnostic yield and cancer death reduction. Implementation requires sonographer training investment and quality assurance. International Ovarian Tumour Analysis Assessment of Different NEoplasias in the adneXa implementation in primary care/community settings, artificial intelligence-enabled quality assurance, reconfiguration of referral pathways in primary care to reduce unnecessary referrals in younger women and consequent harm are important research areas. Systematic symptom elicitation capitalising on routine health interactions to reach underserved communities warrants further research. This synopsis presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number 13/13/01. When women go to their doctor with symptoms like bloating or new tummy pain or feeling full after meals or changes in toilet habits, they need tests to find out what is wrong. A tiny proportion of women with these symptoms will have ovarian cancer. We know that when caught at Stage I, more than 9 out of 10 women will survive the cancer, whereas this drops to 1–2 women when diagnosed at Stage IV cancer. Diagnosing ovarian cancer earlier will save lives and reduce the complexity and side-effects of treatment. For many years, doctors have used a test called Risk of Malignancy Index, which combines blood tests and simple ultrasound scans to determine the risk of a person having ovarian cancer. We wanted to find out if newer tests might work better and understand how much these different tests cost the National Health Service. Our research had several parts. First, we looked at all the previous studies about these tests, including information from over 30,000 women. Then, we did our own large study called ROCkeTS, where we tested 2453 women who attended hospital for the first time with these symptoms in 23 hospitals across the United Kingdom between 2015 and 2023. Each woman in our study had a blood test, a detailed ultrasound scan conducted by staff who had undergone specific training, and filled in a questionnaire about their symptoms. We collected data on whether participants underwent surgery or a biopsy within 3 months of joining the study. If they did not need surgery or biopsy, we followed them up for at least a year to make sure they were well. The old test (Risk of Malignancy Index) was not very good at finding cancer in younger women who have not been through the menopause – it missed more than half of the cancers. A newer test called International Ovarian Tumour Analysis Assessment of Different NEoplasias in the adneXa was much better at finding cancer, though it sometimes suggested women might have cancer when they did not. We found big differences in the number of women diagnosed with cancer between younger and older women. About 3 in 100 younger women and 18 in 100 older women referred to hospital for further checks were diagnosed with ovarian cancer. The new Assessment of Different NEoplasias in the adneXa ultrasound test is more detailed than current ultrasound tests and requires special training. It is like learning a new language – staff need to learn exactly how to describe what they see on the ultrasound in a very specific way. This means all sonographers (the non-medical specialists who do ultrasound scans) need specific training and regular checks to make sure they are doing the test correctly. In our study, we found that when staff were trained, the Assessment of Different NEoplasias in the adneXa test could find 9 out of 10 cancers. This is a big improvement that could help save lives. The International Ovarian Tumour Analysis Assessment of Different NEoplasias in the adneXa test also flagged up more than twenty women out of a hundred as potentially having cancer when they actually did not. We also looked carefully at how women felt about having these tests. Many women felt very anxious while having tests, especially younger women. Even when tests showed nothing was wrong, many women still worried about cancer a year later. However, when cancer was found because women had been referred by their general practitioners for suspicion of cancer, it was often caught at an early stage when treatment works better – about a quarter of the most aggressive type of ovarian cancers were found early. This suggests that referring women with symptoms for testing helps them get diagnosed early and have more successful treatment. When we looked at costs, we found that while the new Assessment of Different NEoplasias in the adneXa test was more expensive than the old Risk of Malignancy Index test, it reduced the chances of death from cancer. Modifying the scan technique by using a two-step strategy with the Assessment of Different NEoplasias in the adneXa test proved the best trade-off between cost and reducing death from cancer. A two-step strategy is where staff first look at ultrasound pictures of the growth. If it has certain innocent features (like being a single smooth-walled cyst), they can immediately tell it is almost certainly harmless – this works for about 3–4 out of every 10 cases. For the other cases that are not so obvious, staff can use the International Ovarian Tumour Analysis Assessment of Different NEoplasias in the adneXa test that looks at more details and gives a risk score. This two-step approach is performed at the same ultrasound examination and makes the process faster and simpler when possible, but still very accurate for all patients, making this approach very suitable for use in the National Health Service. The challenge now is to roll out this better test across the National Health Service. This means training sonographers in the new technique, setting up systems to check the quality of their work regularly, making sure that doctors know how to interpret the results of the scan and make decisions based on the Assessment of Different NEoplasias in the adneXa test, supporting staff to learn and use the new system confidently and finding ways to reduce waiting times for scans. Based on our research, we recommend that hospitals should switch to using the new Assessment of Different NEoplasias in the adneXa test using the two-step approach instead of the old Risk of Malignancy Index test. While this will take time and money to implement properly, it could make a real difference to women’s lives by finding cancer earlier when it is easier to treat. We also need to find better ways to support women who are worried while having tests, and research into whether International Ovarian Tumour Analysis Assessment of Different NEoplasias in the adneXa ultrasound can be used in primary care to identify women with ovarian cancer earlier and to reduce the number of women (particularly younger women) referred to hospital for more checks. An exciting area of future research is developing computer programs using artificial intelligence to help with ultrasound scans. These artificial intelligence tools could help reduce the long waiting times for ultrasound tests in the community and make sure everyone gets the same high-quality scan wherever they live. Our research has also found that when women present to their general practitioners with symptoms and they are then investigated and referred to hospital using fast track pathways, their ovarian cancer can be diagnosed early with better chances of treatment. Asking people about their symptoms during regular doctor visits may be a good way to reach underserved communities. Scientists should study this approach to see if it helps. In summary, our research has helped doctors choose the best test for women who might have ovarian cancer, which should help find cancer earlier when it is easier to treat, while making the best use of National Health Service resources.

HomeHealth is a home-based, voluntary sector service supporting older people with mild frailty to maintain independence through behaviour change. Support workers discuss the person's priorities and enable setting/achieving goals around mobility, nutrition, socialising and/or psychological well-being. We tested clinical and cost-effectiveness of HomeHealth for maintaining independence in older people with mild frailty in a randomised controlled trial. Design: Single-blind, parallel randomised controlled trial open between 18 January 2021 and 4 July 2023, with mixed-methods process evaluation. Setting: Community-dwelling older people aged 65+ years with mild frailty from 27 general practices and community settings in London, Yorkshire and Hertfordshire. Randomisation: Participants were randomised 1 : 1 to receive HomeHealth or treatment as usual. Outcomes: Primary outcome was independence in activities of daily living (modified Barthel Index), analysed using linear mixed models. Secondary outcomes included frailty phenotype score, extended activities of daily living, well-being, psychological distress, loneliness, cognition, falls and mortality. Health economic outcomes included quality of life, capability and service use, including hospital admissions. Cost-effectiveness acceptability curves and cost-effectiveness planes were used to represent the probability of cost-effectiveness compared to treatment as usual. Process evaluation: We conducted semistructured interviews with participants receiving the intervention, HomeHealth workers and other stakeholders supporting service delivery. Interviews were thematically analysed. Fidelity of audio-recorded appointments was assessed by two independent raters. We evaluated potential mechanisms of impact using data from appointments attended, types of goals set and progress towards goals. We recruited 388 participants, mean age 81.4 years (standard deviation 6.5), 64% female and 94% White British/European. HomeHealth did not improve Barthel Index scores at 12 months (0.250, 95% confidence interval -0.932 to 1.432). At 6 months, we found small significant reductions in psychological distress (-1.237, 95% confidence interval -2.127 to -0.348), and frailty phenotype score (-0.252, 95% confidence interval -0.487 to -0.017). At 12 months, we found significant improvements in well-being (1.449, 95% confidence interval 0.124 to 2.775), reduced unplanned admissions (incidence rate ratio 0.65, 95% confidence interval 0.54 to 0.92) with lower associated costs (-£586/participant, 95% confidence interval -351 to -821). There were no differences in other outcomes. HomeHealth dominates treatment as usual with a negative point estimate for incremental costs (-796, 95% confidence interval -2016 to 424), positive point estimate for incremental quality-adjusted life-years (0.009, -0.021 to 0.039) and high probability of cost-effectiveness. Process evaluation: Sixty-four semistructured interviews were completed, including 49 participants and 15 HomeHealth workers/stakeholders. The service was acceptable and safe, with good fidelity of delivery. Participants made progress on personalised goals, most working on enhancing mobility. They found the service empowering, and received emotional/practical support. Engagement was more challenging when participants identified no need for change, had significant memory impairment or new/declining illness. Flexibility around varying symptoms and incorporating behaviour change into existing routines promoted engagement. HomeHealth did not improve independent functioning for older people with mild frailty. There were small significant improvements in frailty status, psychological distress and well-being and a 35% reduction in unplanned admissions, with high probability of cost-effectiveness. We used a pragmatic design with intervention delivery in real-world settings during/after the COVID-19 pandemic, potentially with more variability in delivery. Our findings might not apply to other geographical settings/healthcare systems. This synopsis presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number NIHR128334. As we age, we may develop several health conditions that affect how we feel and our ability to manage without help. For some, it can mean they have less energy and muscle strength, and it is harder to do routine tasks such as shopping or cooking. Few services exist to prevent things getting worse. We designed a new service, ‘HomeHealth’, to enable older people to maintain their independence and activities they enjoy. Over six visits with a dedicated support worker, they identified concerns such as tiredness, low mood and anxiety, poor appetite, weakness and memory problems and developed goals and plans to address difficulties. Our research aimed to explore if HomeHealth helped people to stay independent for longer and provided value for money. Our study recruited 388 older people who were struggling with their everyday activities like cooking/shopping and getting out due to their health. Half were randomly allocated to the HomeHealth service, and half received usual care for 6 months. All participants were assessed by researchers at the beginning, 6 and 12 months later. We also interviewed 49 participants, and 15 people delivering the service about their experiences. We found that HomeHealth did not improve participants’ independence compared to usual care, though it showed small positive effects on mood and frailty at 6 months and well-being after 1 year. Those receiving the service were 35% less likely to be admitted to hospital for acute illness and had lower hospital care costs. The service was acceptable, safe, provided emotional and practical support and empowerment. Most older people made progress on goals to improve their health and well-being. Some found this more challenging, particularly those with worsening health or memory, or those who felt no need to change. The HomeHealth service is a promising intervention to reduce unplanned (emergency) hospital admissions.

Tuberculosis remains a United Kingdom health concern. It occurs predominantly in people who have lived in tuberculosis endemic countries or have links there. Adherence to anti-tuberculosis treatment can be challenging, especially for people who experience severe side effects or social marginalisation. Poor adherence can lead to treatment failure. Current adherence support interventions make little difference to outcome. We identified the need for a 'manualised' approach to (1) improve case-managers' ability to detect people likely to non-adhere and (2) guide targeted adherence support. Synthesise knowledge on drivers and interventions to support anti-tuberculosis treatment adherence Apply the Perceptions and Practicalities framework to understand poor adherence Develop a manualised intervention to identify adherence-related risks, modifiable barriers and support mechanisms Pilot the intervention and assess feasibility of data collection Evaluate implementation through fidelity and reach, and assess impact on adherence Assess intervention delivery costs to guide a full trial plus economic evaluation. The study ran April 2018-September 2022. Formative work included scoping reviews of adherence literature; National Health Service patients, caregivers, and health worker interviews; and clinic observations. A multidisciplinary group, including people with lived experience of tuberculosis, healthcare professionals, and researchers, coproduced the intervention package. We performed a (1 : 1) pilot cluster-randomised trial (N = 79 participants evaluated), randomising four London tuberculosis clinics, in preparation for a definitive cluster-randomised trial. Participants in control clinics received standard care. The primary outcome was adherence, doses taken of a possible 168 measured using evriMED boxes and other sources. We recorded treatment outcomes and changes in participants' needs, health-related beliefs and perceptions, costs, and health status. We conducted a mixed-methods process evaluation, using questionnaires, interviews, case-report forms, checklists and clinic observations. Electronic tuberculosis needs assessment completed at all visits. Two animated videos to increase motivation and ability to take treatment. Interactive treatment guide designed around the Perceptions and Practicalities framework. Detailed manual for case managers. We developed a tuberculosis needs assessment for tuberculosis services. This appeared better than standard care at identifying people requiring adherence support [e.g. at baseline 21/36 (58.3%) intervention vs. 4/43 (9.3%) control] and social support (over 24 weeks, on 29 vs. 6 occasions respectively). Cumulative dose-taking was high across the study population at 24 weeks [84% (95% confidence interval 78-91%) overall; 81% (68-93%) intervention; 88% (67-100%) control]. Dose-taking patterns were similar between arms. The videos and booklet produced short-term improvements in beliefs, necessity, concerns and practical barriers. Collecting health economic data using self-completed questionnaires was feasible; retrieving data from records more challenging. The intervention was acceptable to patients and staff though took longer than control to perform. Study sample contained few people more likely to non-adhere. Assessments may have altered intervention's effects. Use of medication monitor in both arms may have affected results. The intervention, a National Health Service first, is feasible to use. Its place in care and method of evaluation could be assessed in a larger, definitive study. This trial is registered as Current Controlled Trials ISRCTN 95243114. IRAS ID: 231542; REC reference number: 18/LO/1818. This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 16/88/06) and is published in full in Health Technology Assessment; Vol. 30, No. 28. See the NIHR Funding and Awards website for further award information. Tuberculosis is a serious infectious disease. It occurs most often in people with links to countries where it is common. Treatment lasts months, and sticking to this (adherence) is not easy. Being non-adherent can make treatment less effective. While we do know that some people are less likely to adhere, we wanted to design, build and test a package that could identify even more of those at risk of non-adherence and offer suitable support. Therefore, we examined the published evidence, interviewed people with tuberculosis, carers and health workers across the United Kingdom, and observed National Health Service tuberculosis clinics. With this, a multidisciplinary team developed a package that assessed patients’ needs and offered videos about tuberculosis, a treatment booklet, and structured support. Between October 2020 and September 2022, we trialled this in a small number of people being treated for tuberculosis in four London clinics: in two, people were offered standard care; in the other two, our care package. We recruited 79 people. We measured adherence, knowledge and beliefs around tuberculosis, health service use and quality of life. We also estimated the intervention’s cost. We found: it was possible to design, build, and test the intervention deliver it within National Health Service, despite COVID collect data on costs for future analysis it was difficult to recruit people at greatest risk of non-adherence to treatment measure changes in people’s beliefs. Our intervention: could identify people’s risk of non-adherence and hence need for support was acceptable to staff and patients, though consultations took longer made short-term changes to people’s beliefs about tuberculosis did not have a substantial effect on adherence. To decide if this should be used more widely, we need to streamline our design and include more patients and clinics in a larger study.

Ovarian hyperstimulation syndrome is a significant complication of fertility treatment, where the ovaries become enlarged if they are overstimulated, resulting in fluid leakage. Ovarian hyperstimulation syndrome can be classified as mild, moderate or severe. Symptoms vary dependent on severity but can include abdominal swelling, pain, nausea and vomiting, and shortness of breath. Treatment typically consists of monitoring initially, with active intervention if the condition progresses to a severe state, requiring hospitalisation. This study explored the acceptability and feasibility of outpatient paracentesis, and of gonadotropin-releasing hormone antagonists, as early interventions for ovarian hyperstimulation syndrome. We conducted qualitative semi-structured interviews with healthcare professionals from fertility clinics (n = 8) and patients who had experienced ovarian hyperstimulation syndrome (n = 10) across six United Kingdom fertility clinics. Interviews explored views on the proposed treatment protocols, and potential barriers and facilitators to randomised controlled trials evaluating these treatments. Both healthcare professionals and patients were supportive of the proposed trials. Key findings included that healthcare professionals recommended clarity on patient eligibility, hospitalisation criteria and consent procedures. Patients expressed a desire to be given more detailed information about potential trials and had mixed opinions on self-monitoring. There were some concerns from both parties about treatment risks, particularly the paracentesis. Healthcare professionals noted a shift to more preventative practice due to the COVID-19 pandemic. Outpatient paracentesis and gonadotropin-releasing hormone antagonists were perceived as promising interventions. Potential concerns and recommendations around both acceptability and feasibility were raised, which were used to refine the treatment protocols for the Shaping and Trialling Outpatient Protocols for Ovarian Hyperstimulation Syndrome trial. This article presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number NIHR128137. This study explored the views of healthcare professionals and patients on proposed treatments for ovarian hyperstimulation syndrome, which is a complication of fertility treatment. During fertility treatment, drugs are given to encourage the ovaries to produce more eggs; sometimes, the ovaries become overstimulated, becoming enlarged and releasing chemicals that affect the bloodstream and fluid in the body. Ovaries becoming overstimulated results in extra fluid being released around the body, leaking into the abdomen and, in severe cases, around the heart and lungs. The symptoms of ovaries becoming overstimulated vary depending on whether it is mild, moderate or severe. Symptoms generally include abdominal swelling or bloating, discomfort and nausea. As ovaries becoming overstimulated worsens, it can lead to increased pain, vomiting, shortness of breath, decreased urine output and, in rare cases, blood clots. The researchers were planning to conduct a trial to assess two potential treatments: outpatient paracentesis (a procedure to drain excess fluid) and gonadotropin-releasing hormone antagonist injections. The researchers interviewed eight healthcare professionals who work in fertility clinics, and ten patients, to ask their opinions on how these trials should be designed. Both healthcare professionals and patients generally supported the idea of these treatments, agreeing that more proactive management is needed. Healthcare professionals wanted clearer guidelines on how to tell how severe ovaries becoming overstimulated is and when to hospitalise patients. They also discussed a current trend towards using more cautious treatment which may prevent ovaries becoming overstimulated, to avoid hospital admissions during the COVID-19 pandemic. Patients suggested that more detailed information should be given to those who may take part in the trial. Patients’ opinions varied on whether they would like to monitor their own symptoms at home – some found it empowering, while others thought it would be difficult. However, most patients liked the idea of avoiding hospital stays unless their symptoms were bad. Both healthcare professionals and patients raised concerns about whether there were treatment risks, particularly for paracentesis, and from healthcare professionals only whether their service had the facilities to be able to carry out outpatient paracentesis. These findings highlighted the need for more training to address these concerns. The researchers used these findings to improve the treatment protocols and trial procedures for their later research trial (called Shaping and Trialling Outpatient Protocols for Ovarian Hyperstimulation Syndrome) on ovarian hyperstimulation syndrome management. This study highlights the importance of considering both healthcare professional and patient perspectives when developing new treatments and clinical trials.

Skin cancers are some of the most common types of cancer. Dermatology services receive about 1.2 million referrals a year, but only a small minority are confirmed skin cancer. Artificial intelligence may be helpful in the diagnosis of skin cancer by identifying lesions that are or are not cancerous. To investigate the clinical and cost-effectiveness of two artificial intelligence technologies: DERM (Deep Ensemble for Recognition of Malignancy, Skin Analytics) and Moleanalyzer Pro (FotoFinder), as decision aids following a primary care referral. A rapid systematic review of evidence on the two technologies was conducted. A narrative synthesis was performed, with a meta-analysis of diagnostic accuracy data. Published and unpublished cost-effectiveness evidence on the named technologies, as well as other diagnostic technologies were reviewed. A conceptual model was developed that could form the basis of a full economic evaluation. Four studies of DERM and two of Moleanalyzer Pro were subject to full synthesis. DERM had a sensitivity of 96.1% to detect any malignant lesion (95% confidence interval 95.4 to 96.8); at a specificity of 65.4% (95% confidence interval 64.7 to 66.1). For detecting benign lesions, the sensitivity was 71.5% (95% confidence interval 70.7 to 72.3) for a specificity of 86.2% (95% confidence interval 85.4 to 87.0). Moleanalyzer Pro had lower sensitivity, but higher specificity for detecting melanoma than face-to-face dermatologists. DERM might lead to around half of all patients being discharged without assessment by a dermatologist, but a small number of malignant lesions would be missed. Patient and clinical opinions showed substantial resistance to using artificial intelligence without any assessment of lesions by a dermatologist. No published assessments of the cost-effectiveness of the technologies were identified; three assessments related to skin cancer more broadly in a National Health Service setting were identified. These studies employed similar model structures, but the mechanism by which diagnostic accuracy influenced costs and health outcomes differed. An unpublished cost-utility model was provided by Skin Analytics. Several issues with the modelling approach were identified, particularly the mechanisms by which value is driven and how diagnostic accuracy evidence was used. The conceptual model presents an alternative approach, which aligns more closely with the National Institute for Health and Care Excellence reference case and which more appropriately characterises the long-term consequences of basal cell carcinoma. The rapid review approach meant that some relevant material may have been missed, and capacity for synthesis was limited. The proposed conceptual model does not capture non-cash benefits associated with demand on dermatologist time. An assessment of the likely budget impact and resource use could not be provided. DERM shows promising diagnostic accuracy for triage and diagnosis of suspicious cancer lesions in selected patients referred from primary care. Its impact on the diagnostic pathway and patient care is, however, uncertain. Moleanalyzer Pro shows promising accuracy for diagnosing melanoma, but its evidence base is limited. While artificial intelligence has the potential to be cost-effective for the identification of benign lesions, further research addressing the limitations in the diagnostic accuracy evidence is necessary. Without comparative evidence on the diagnostic accuracy of artificial intelligence technologies, their value will remain uncertain. This study is registered as PROSPERO CRD42023475705. This award was funded by the National Institute for Health and Care Research (NIHR) Evidence Synthesis programme (NIHR award ref: NIHR136014) and is published in full in Health Technology Assessment; Vol. 30, No. 10. See the NIHR Funding and Awards website for further award information. Skin cancers and suspicious skin lesions are very common. People with moles or lesions that might be cancerous are referred to a skin cancer specialist (a dermatologist) to make a diagnosis. This places a very high burden on dermatology clinics and, as a result, there can be delays in seeing a dermatologist and getting a diagnosis. Artificial intelligence systems could potentially use a high-quality photograph to identify which lesions do not need to be seen by a specialist. This could be done by the artificial intelligence system alone, or in combination with remote review by a dermatologist. This project investigated whether two artificial intelligence technologies: DERM (Skin Analytics) and Moleanalyzer Pro (FotoFinder) could be useful in reducing the burden on dermatology services while helping to identify skin cancer. The evidence was reviewed to investigate whether the technologies can accurately identify skin cancer cases, and whether their use might improve the diagnosis process for patients. We also designed a theoretical model in which the economic value of artificial intelligence technologies for the diagnosis of skin cancer could be assessed. As part of this process, we sought to outline what further evidence would be needed to implement a full assessment. The evidence we reviewed suggests DERM could potentially reduce by half the number of patients that would be referred to specialist dermatologists, while still identifying 95% of all skin cancers. Moleanalyzer Pro could identify about 85% of malignant melanomas. This appears to be a similar accuracy to that achieved by using a remote view of the lesions by dermatologists alone. How DERM or Moleanalyzer Pro use would impact diagnosis and treatment for patients in practice, and the burden on clinicians, is currently unclear. Because of limitations in the evidence on the diagnostic accuracy of artificial intelligence technologies, a full assessment of their economic value is not possible at this time. Further research should focus on better establishing the diagnostic accuracy of both artificial intelligence technologies and current service provision.

Many diseases, including breast cancer, have a long natural history; therefore, longer-term effects of treatments are important for patients and for their full evaluation. However, trial follow-up data are collected by specific staff and are funded for a relatively short duration. We evaluated whether we could collect follow-up information for patients in a breast cancer randomised clinical trial by direct patient contact and data from national registries. The TARGIT-A randomised clinical trials of targeted intraoperative radiotherapy during lumpectomy versus whole-breast external beam radiotherapy&#xa0;(n=2298), and delayed TARGIT-IORT vs. external beam radiotherapy (n&#x2005;=&#x2005;1153), recruited women with early breast cancer diagnosed in 33 centres in 12 countries, between March 2000 and June 2012. We planned to recruit all United Kingdom patients from the TARGIT-A trials for extended follow-up. These were the first randomised trials of intraoperative radiotherapy for breast cancer. We assessed the feasibility of recording whether patients are alive and their current health status, including events related to breast cancer, and effects of radiotherapy such as lung cancer diagnoses, by direct patient contact and data from NHS Digital (health episodes, diagnoses and death). Patients were consented in collaboration with the recruiting site and were then contacted annually, if appropriate, directly by the trial centre. We calculated the proportion of eligible patients whose status could be ascertained, contacted, consented and provided follow-up information via direct patient contact and/or NHS Digital data. We estimated the additional years of follow-up and its cost. Six hundred and seven of 714 United Kingdom patients originally recruited in the TARGIT-A trials were initially eligible. We ascertained the current status or reason for non-participation of 574 (94.5%); 87% (502/574) of these patients' health status could be determined. Of these, 73% (366/502) or 60.3% of the total (366/607) were found to be in good health, provided valid consent for TARGIT-X and their health status. One hundred and thirty-six patients did not participate in TARGIT-X because: 105/136 (77%) were too unwell or had died, and for 6 patients, the consent was either incomplete or the physical form could not be traced. Less than 5% (25/502) of patients were unwilling to participate: 23 declined and 2 withdrew. We recorded an additional 103 deaths, more than doubling the initial number to 203. The quality of data returned by patients was very good [e.g. mismatch rate for recording date&#x2005;<&#x2005;0.1% (1/1470 forms)]. Patients who participated increased their follow-up by a median 6 years [to 14 years (interquartile range 13-16)]. We found a much lower incidence of lung cancer diagnoses with TARGIT-IORT compared with EBRT (16-year incidence 1.8% vs 7.2%). The cost, including research funds, was&#x2005;<&#x2005;&#xa3;60/patient/year of follow-up. Limitations included difficulties in receiving data from NHS Digital due to their repeated organisational changes, plus unexpected price rises in the costing of data download. We were able to establish direct contact with the patient while they are alive, as well as gathered data from the national registries about their hospital episodes/new diagnoses and checked if they had died. Another strength is that despite the study management being considerably disrupted due to the COVID-19 pandemic (2020-present), which erupted in the midst of the study (2017-24), we believe we have shown that the approach is an effective means of continuing follow-up in the United Kingdom. A limitation of our approach is that the initial consent from the patient requires the site principal investigators to contact the patient, but this is just once. If consenting for direct patient contact and data collection from national registries is included in the initial trial set up, then our approach will enable very long-term follow-up of clinical trials. We recommend a study of using electronic secure systems for direct patient contact from the outset of a clinical trial to investigate the organisational and systemic bottlenecks in NHS Digital services, with a view to reduce bureaucracy and cost, and to investigate why results of large international well-conducted randomised trials that have been shown to be beneficial to patients and cost-effective to the health system are not widely adopted in the United Kingdom, while they are included in almost every other country's clinical practice guideline and get widely adopted worldwide to assess the influence of preconceived notions, conflicts of interest, that could prompt improvements in the National Institute for Health and Care Excellence processes. In the United Kingdom, 95% of patients are willing to be followed up in the long term. It is feasible to collect follow-up data for long-term health conditions accurately from patients with direct patient contact together with NHS Digital. It leads to a substantial increase in the length of follow-up and number of relevant events, at a low cost. Our new approach could be adopted as an efficient method of obtaining long-term follow-up data from patients in randomised clinical trials. This trial is registered as Current Controlled Trials ISRCTN (ISRCTN86287193) and ClinicalTrials.gov (NCT03501121) in April 2018, UK R&D ID Number: 17/0774, Ethics - REC reference: 18/LO/0181. This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 14/49/13) and is published in full in Health Technology Assessment; Vol. 30, No. 29. See the NIHR Funding and Awards website for further award information. As patients with breast cancer live far longer, and treatments have long-term effects, follow-up longer than normally funded is important for patients, clinicians and policy-makers. We evaluated (TARGeted Intraoperative radioTherapy-X study) whether we could collect follow-up data by &#x2018;direct patient contact&#x2019; with which the patient could update the trials unit with their health status directly and from NHS Digital. We had recruited (March 2000&#x2013;June 2012) 3451 patients in the TARGeted Intraoperative radioTherapy-A randomised clinical trials, which compared single-dose targeted intraoperative radiotherapy versus standard of postoperative whole-breast external beam radiotherapy given as daily doses over a course of 3&#x2013;6 weeks. Six hundred and seven of 714 UK patients were eligible. The health status or the reason for non-participation was available for 574 (95%), and health status was determined in 87% of cases (502/574). Of these, 73% (n&#x2005;=&#x2005;366, 60.3% of the total) were healthy and participated. Of the patients who did not participate, 105/136 (77%) were too unwell or had died, 23 declined and 2 withdrew, and in 6, consent was invalid. Less than 5% (25/502) of patients declined participation. We doubled our knowledge about survival (recorded deaths increased from 100 to 203). Patients recorded their own data very accurately: only 1 error among the 1470 case report forms &#x2013; an error rate of&#x2005;<&#x2005;0.1%. NHS Digital adds substantially to the number of events and lengthens the available follow-up. The length of follow-up increased by 6 years, to a median of 14 years (interquartile range 13&#x2013;16). We found that using TARGIT-IORT reduced lung cancer incidence by two-thirds compared with EBRT. The cost was < &#xa3;60 per patient per year of follow-up. We conclude that in the UK, it is feasible and cost-effective to roll out direct patient contact as a method of accurate long-term follow-up of patients at a low cost. Our new approach could be adopted as an approach in other randomised clinical trials.

Accessible occupational health advice is only available to approximately half the United Kingdom population. With rising sickness absence new models for delivering occupational health are required to support employees with health conditions to manage their condition at work. To determine, in patients consulting in general practice who receive a fit note, whether the addition of a vocational advice intervention to usual primary care leads to fewer days lost from work, and whether vocational advice is cost-effective. Intervention development: Training development using mixed methods and the theoretical framework the Behaviour Change Wheel. Feasibility study: Mixed methods, single-arm feasibility study, with stop/go criteria to assist decision making about progression to full trial. Trial: Multi-centre, two-parallel arm, superiority, randomised controlled trial with health economic analysis and nested qualitative study. General practices in three geographic areas in England: West Midlands, South London and Wessex. Patients aged &#x2265;&#x2005;18 years, currently in paid employment (full or part-time), current absence from work of at least 2 weeks but not more than 6 consecutive months, with a fit note for any health condition. Vocational advice delivered by trained vocational support workers plus usual primary care (intervention arm), compared to usual primary care alone (control arm). The outcome of intervention development was a vocational advice intervention and training package. Feasibility study outcomes were ability to recruit and acceptability of the vocational advice intervention to participants. The trial primary outcome was number of days absent from work over 6 months. A vocational advice intervention and training package designed for delivery in primary care using case management and stepped care to support patients absent from work for 2 weeks to 6 months. The feasibility study recruited 19 participants demonstrating the vocational advice intervention could be delivered and was acceptable to participants. Recommendations around automated recruitment and data collection were made which were implemented in the trial. The randomised controlled trial sample size was 720; 130 participants were recruited (66 intervention/64 control) before closing early due to recruitment difficulties. There was no statistically significant difference in days absent over 6 months with a mean of 37 (standard deviation 48) days absence (vocational advice intervention) compared to a mean of 42 (standard deviation 57) days absence (usual primary care alone) and an adjusted incidence rate ratio of 0.913 (80% confidence interval 0.653 to 1.276). Health economic analysis found that productivity losses were also lower in the intervention arm at &#xa3;5513.84 (standard deviation &#xa3;7101.43) compared to the control arm at &#xa3;6146.21 (standard deviation 8431.88). At 6 weeks, the intervention arm had lower mean absenteeism, presenteeism, work productivity loss and activity impairment on the work productivity activity impairment scale than the control arm; again this was not significant. This study resulted in a vocational advice intervention suitable for all health conditions and a training package to support delivery of the intervention. In primary care, delivery was feasible and acceptable to patients. Exploratory analysis indicated some signals of benefit in terms of days absent from work, costs and most other secondary outcome measures. Future work should focus on the delivery of a fully powered randomised controlled trial evaluating an early vocational advice intervention compared to usual primary care to determine the effectiveness and cost-effectiveness of this approach. This synopsis presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number 17/94/49. People&#x2019;s health often impacts their ability to work, but most people do not have access to occupational health. The Work And Vocational advicE study aimed to find out whether adding a vocational advice intervention to usual primary care helped people off work for any health condition for between 2 weeks and 6 months, to have fewer days off work than those who did not get the vocational advice intervention. Three phases of research were carried out: intervention development: designing the vocational advice intervention feasibility study: testing the plans for the trial methods ted randomised controlled trial, patients were randomly assigned to the vocational advice intervention plus usual primary care or usual primary care alone. The outcome was number of days absence over 6 months. A vocational advice intervention and training package was designed to support patients with any health condition, absent from work for 2 weeks to 6 months. The feasibility study recruited 19 participants demonstrating the vocational advice intervention could be delivered and was acceptable. The randomised controlled trial recruited 130 participants (66 to the vocational advice intervention/64 to usual primary care alone), before closing early. There was a non-significant difference in days absent over 6 months with the intervention arm reporting 4.8 fewer days absence compared to the control arm. Health economic analysis reported productivity losses were lower in the intervention arm at &#xa3;5513.84 (standard deviation &#xa3;7101.43) compared to the control arm at &#xa3;6146.21 (standard deviation 8431.88). We developed a vocational advice intervention and training to support delivery of the intervention. The feasibility study found delivery was feasible and acceptable, but recruitment needed improvement. Exploratory analysis found signals of benefit in days absent from work, costs and most other measures. Future work should deliver of a fully powered randomised controlled trial evaluating an early vocational advice intervention compared to usual primary care to be sure of the effectiveness and cost-effectiveness.

Bariatric surgery can improve health outcomes but high-quality comparative evidence about different procedures is limited. To compare the effectiveness and cost-effectiveness of Roux-en-Y gastric bypass (Bypass), adjustable gastric banding (Band) and sleeve gastrectomy (Sleeve) for people living with severe obesity. Multicentre, parallel-group, randomised controlled trial conducted in 12 National Health Service hospitals. Adults with a body mass index &#x2265;&#x2005;35&#x2005;kg/m2 with comorbidity or body mass index &#x2265;&#x2005;40&#x2009;kg/m2 without comorbidity were eligible. Participants were initially randomised 1&#x2005;:&#x2005;1 to Bypass or Band. After 32 months of recruitment, the trial was adapted to include Sleeve, and participants were randomised to Bypass, Band or Sleeve thereafter. Participants were followed up for 3 years. Bypass, Band and Sleeve surgery. Primary outcomes were self-reported quality of life (EQ-5D-5L utility score) and weight (at least 50% excess weight lost) at 3 years. Sleeve and Bypass were each considered superior to Band if there was non-inferior excess weight loss (<&#x2005;12% difference between groups) and superior quality of life. Sleeve was considered superior to Bypass by the same criteria. Secondary outcomes included comorbidities, adverse health events, generic and disease-specific quality of life at 6, 12, 24 and 36 months post randomisation, dietary intake, binge eating behaviour and cost-effectiveness. One thousand three hundred and fifty-one participants were randomised between December 2012 and September 2019. Five participants withdrew consent to use their data, leaving 1346 (462 Bypass, 464 Band, 420 Sleeve). The mean age was 47.3 years, 1020 (75.9%) were women and the mean weight and body mass index was 129.7&#x2009;kg and 46.4&#x2009;kg/m2, respectively. Overall, 1183 (87.5%) of participants underwent surgery within 3 years, with a median waiting time of 5 months (interquartile range 2.5-10.1 months). At least 50% excess weight loss at 3 years was achieved for 276/405 (68.1%) participants randomised to Bypass, 97/383 (25.3%) randomised to Band and 142/342 (41.5%) randomised to Sleeve [adjusted risk difference (Bypass-Band) +&#x2005;40.7%, 98% confidence interval (+&#x2005;33.9% to +&#x2005;47.5%); (Sleeve-Band) +&#x2005;14.7% (+&#x2005;5.2% to +&#x2005;24.2%), (Sleeve-Bypass) -26.0% (-35.8% to -16.3%)]. Mean EQ-5D scores at 3 years were 0.72 (standard deviation 0.29), 0.62 (0.33) and 0.68 (0.30) for participants randomised to Bypass, Band and Sleeve, respectively [adjusted mean difference (Bypass-Band) +&#x2005;0.079 (+&#x2005;0.040 to +&#x2005;0.117), (Sleeve-Band) +&#x2005;0.045 (+&#x2005;0.006 to +&#x2005;0.085), (Sleeve-Bypass) -0.033 (-0.072 to +&#x2005;0.006)]. Secondary outcomes showed similar trends. The adverse event rate was highest in the Band group and lowest with Sleeve. Bypass was the most cost-effective procedure, with probabilities <&#x2005;0.3 that Sleeve or Band was the most cost-effective. The study was impacted by the COVID-19 pandemic which prevented some participants having surgery and/or attending hospital for study follow-up appointments, which impacted on the completeness of data for these visits. Bypass and Sleeve are more effective than Band. Sleeve has inferior excess weight loss and lower mean quality-of-life score than Bypass. Longer-term follow-up is needed to determine the sustainability of observed effects and to examine adverse events. A comparison of optimal gastric bypass and optimal medical therapy for severe obesity is now needed to inform decision-making and health policy. This trial is registered as ClinicalTrials.gov: NCT02841527, ISRCTN00786323. This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 09/127/53) and is published in full in Health Technology Assessment; Vol. 30, No. 6. See the NIHR Funding and Awards website for further award information. People who are overweight or obese may benefit from surgery to lose weight (bariatric surgery), improve quality of life and health. While several operations are available, it is uncertain which procedure leads to the best results for patients and the National Health Service. One thousand three hundred and forty-six adults with severe obesity referred for bariatric surgery from 12 hospitals in the United Kingdom. The people who took part were allocated by chance to one of three surgical procedures aimed at achieving weight loss: gastric bypass, gastric band or sleeve gastrectomy. Participants were followed up for 3 years. We collected information on weight loss, blood markers, diet, hospital visits and safety information (e.g. side effects) over this period. Participants were also asked to complete questionnaires about their health-related quality of life and income. The people having bypass surgery and sleeve surgery had greater weight loss and better quality of life at 3 years compared to those people having band surgery. Bypass surgery led to greater weight loss compared to sleeve surgery. There were fewer side effects after sleeve surgery compared to bypass and band surgery. Bypass surgery was found to provide the best value for money for the National Health Service.

Gabapentin is an anticonvulsant medication with a United Kingdom licence to treat partial seizures and neuropathic pain. It is used off-licence for acute pain and is frequently added to multimodal analgesic regimens after surgery to try and reduce opioid use while controlling pain effectively. To test the hypothesis that gabapentin reduces opioid use after major surgery and speeds up recovery, thereby reducing postoperative hospital length of stay compared to standard multimodal analgesia. The GAP study was a multicentre, blinded, randomised controlled trial in patients aged &#x2265;&#x2005;18 years, undergoing cardiac, thoracic or abdominal surgery with an expected postoperative stay of &#x2265;&#x2005;2 days in seven National Health Service hospitals. The trial was designed to provide 90% power to detect a difference of 12.5% in the proportion of participants discharged by the median length of stay in each specialty (500 participants/specialty), which was reduced to 80% (340 participants/specialty) due to COVID-19-related recruitment challenges. Participants were randomised 1&#x2005;:&#x2005;1 (stratified by surgical specialty) to receive either gabapentin (600&#xa0;mg before surgery, 300&#xa0;mg twice daily for 2 days after surgery) or placebo as an adjunct to multimodal pain regimens. Primary outcome was length of stay. Secondary outcomes included acute and chronic (Brief Pain Inventory) pain, total opioid use, adverse health events, health-related quality of life (-EQ-5D-5L, Short Form questionnaire-12 items physical component score and mental component score), resource use; cost-effectiveness (outcome measure quality-adjusted life-years using EQ-5D, five-level version). One thousand one hundred and ninety-six (cardiac 500, thoracic 346, abdominal 350) participants consented and were randomised. Baseline characteristics were well balanced across the two groups: median age: 68 years; male sex 796/1195 (66.4%). Of the participants, 223/1195 (18.7%) did not receive all prescribed medication or received medication out of window. There was no difference in length of stay; median placebo (n&#x2005;=&#x2005;589): 6.15, gabapentin (n&#x2005;=&#x2005;595): 5.94 days [hazard ratio for discharge 1.07, 95% confidence interval (0.95 to 1.20), p&#x2005;=&#x2005;0.26]. Opioid use in-hospital differed between surgical specialties (p&#x2005;=&#x2005;0.001); in the abdominal specialty, it was significantly lower in the gabapentin group in 4 of the first 5 postoperative days [range -26% (-46% to 0%) to -36% (-52% to -14%)], with no differences in the cardiac specialty nor in the thoracic specialty beyond day 2. During follow-up, opioid use was similar in the two groups across all specialties. Acute pain beyond 24 hours was similar (p&#x2005;&#x2265;&#x2005;0.15). The incidence of one or more serious adverse events was placebo: 189/595 (31.7%); gabapentin: 195/599 (32.6%). Health-related quality of life was similar [EQ-5D: mean difference -0.014 (-0.036 to 0.009), Short Form questionnaire-12 items physical component score: -0.87 (-1.71 to -0.04), Short Form questionnaire-12 items mental component score: at 4 weeks 0.74 (-1.71 to 0.42) and 4 months -0.55 (-1.61 to 0.51)]. Differences in costs and quality-adjusted life-years favoured placebo, and gabapentin was not considered cost-effective. GAP study tests the application of gabapentin to major body cavity surgery, but not major non-body cavity surgery, or non-major surgery. The fixed dose and limited duration of gabapentin may reduce applicability to certain populations. Reducing the power to 80% reduced the ability of the trial to detect a beneficial effect of gabapentin. Among patients undergoing major cardiac, thoracic and abdominal surgery, adding gabapentin to multimodal analgesic regimes did not result in a change in length of stay, opiate use in two specialties, acute pain, or health-related quality of life, nor was it cost-effective. Trials to assess the place of gabapentin in major non-body cavity surgery (e.g. joint replacement), or non-major (e.g. day-care) surgery should be considered. This trial is registered as Current Controlled Trials ISRCTN63614165. This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 15/101/16) and is published in full in Health Technology Assessment; Vol. 30, No. 9. See the NIHR Funding and Awards website for further award information. Gabapentin is a medicine used to treat epilepsy and pain caused by damaged nerves. Doctors have recently been using gabapentin to treat pain after an operation, with the intention of reducing the amount of morphine-type drugs (called &#x2018;opioids&#x2019;) needed while maintaining good pain relief. Doctors want to try to reduce the amount of opioid drugs because they cause side effects (such as dizziness and reduced breathing rate), often delaying discharge from hospital and leading to slower recovery. There is uncertainty about whether adding gabapentin to the usual painkilling drugs will result in good pain relief, with fewer side effects, and therefore faster recovery after surgery. One thousand one hundred and ninety-five adults having major heart, lung or abdominal surgery who were expected to stay in hospital for at least 2 days after their surgery. The participants were given either gabapentin or placebo (the same tablet but with no active drug) just before and twice daily for 2 days after their surgery. We measured how long they stayed in hospital after the surgery, the amount of opioid drugs they used, the amount of pain they had, what their quality of life was and how much they cost the National Health Service. We measured these during their hospital stay and at 4 weeks and 4 months after the surgery. The trial found that there was no difference in the length of hospital stay, the number of adverse health events, or National Health Service costs between people who took gabapentin and those who took the placebo. People who took gabapentin for abdominal and thoracic surgery used fewer opioid-type drugs in-hospital after their surgery &#x2013; but this did not translate into better pain control or fewer side effects. Therefore, this trial tells us that doctors should stop routinely giving gabapentin to people to reduce their pain after major surgery.

Repetition of self-harm in prisoners is common but approaches to assess and manage risk of repetition are inconsistent and unstructured. To develop and validate a risk model for repeat self-harm in people in prison, and test feasibility and acceptability. In seven English prisons, we identified 754 people aged over 17 who had been placed on a suicide risk management plan (known as an Assessment, Care in Custody and Teamwork) after a self-harm episode or elevated risk. We developed a multivariable model to estimate risk of repeat suicidality at 3 months using routinely collected sociodemographic, clinical and prison-related factors, which were tested using Cox proportional hazards models. We tested 25 potential risk factors comprising sociodemographic factors, clinical history and treatment, and criminal records using routinely collected information. In a prospective validation sample of 390 people from 13 prisons, we tested this model to assess risk of repeat suicidality at 3 months across a range of performance measures. TRIPOD guidelines were followed for the design and reporting of this work. In a parallel study, we qualitatively ran separate focus groups for prison staff and people in prison to examine practical issues relating to the potential use of a new tool, and synthesised themes. In the overall final sample of 1144 people in prison [966 (84%) men, mean age 33 years], 22% had the outcome of repeat suicidality over 3 months. The final risk model consisted of 9 factors, including sex, calendar age, and features of recent suicidal behaviour. Calibration and discrimination were similar in both development and validation samples, with O:E ratio&#x2005;=&#x2005;1.09 (95% confidence interval 0.88 to 1.35) and c-statistic&#x2005;=&#x2005;0.66 (95% confidence interval 0.60 to 0.72) in external validation. At a 25% cut-off, sensitivity was 58% (50-66%) and specificity 72% (68-75%) in external validation. The tool (Risk Assessment for people in Prison at risk of Self-harm and Suicide or RAPSS) is available as an online risk calculator at https://oxrisk.com/rapsstrial/ and could be used towards the end or on completion of an existing suicide risk management plan. The qualitative study, conducted with multidisciplinary staff groups and two prisoner groups (one male and one female), led to eight themes being identified. Two prominent ones were staff saying that they would be keen to use the tool as a way to identify needs and signpost to other services, and people in prison explaining that any risk tool could help build rapport with their offender manager and support them to access psychological treatments and other services. We have developed and externally validated a brief structured tool that could act as a therapeutic bridge between the closure of a suicide risk management plan and aftercare provision for people at risk of repeat self-harm in prison. Feasibility work examining how to implement the Risk Assessment for people in Prison at risk of Self-harm and Suicide (RAPSS) tool into practice is necessary, and linking interventions to risk scores. The risk model did not test symptoms as possible factors as these were unreliably documented. This synopsis presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number 16/159/09. In this study, we aimed to improve how people with repeat self-harm and suicidal behaviour are supported following an initial assessment process. To do this, we developed and tested a new approach to identify the risk of repeat self-harm, and we talked to prison staff and people in prison about how and when it could be used. We then tested to see if the new tool was accurate. The study involved collecting existing information from more than 1000 adults in prison from seven different prisons who had already had experience of repeat self-harm or suicidal behaviour during their current period in custody. The information collected on these people were combined to identify common elements that were found to elevate risk of self-harm and suicidal behaviour in the subsequent 3 months in 13 prisons. Nine common characteristics (e.g. someone's age; sex at birth; previous self-harm behaviour, and aspects of their most recent suicidal behaviour) were found to identify similarities across those individuals who were at risk. We tested out the new tool in 13 prisons to see if these nine factors were able to accurately identify the future risk in people who had a prison history of self-harm and/or suicidal behaviour. The tool was found to be clearly better than chance at identifying people who were at risk. Using focus groups, we talked to staff working in custody and people in prison to identify what they thought about the new tool. This helped the research team to work out how the tool could be used in practice. Staff and people in prison welcomed the new approach and identified some key requirements that would help implement the tool. These included building rapport with staff administering the tool, supporting people in prison with psychological treatments, and being able to signpost those in need after their initial assessment.

Return to work is achieved by <&#x2005;50% stroke survivors. Evidence on support for return to work is lacking. To determine whether Early Stroke Specialist Vocational Rehabilitation is more clinically effective and cost-effective at supporting return to work 12 months after stroke than usual care. Pragmatic, observer-blind, multicentre superiority randomised controlled trial with embedded health economic evaluation. Participants were individually randomised, 5&#x2005;:&#x2005;4, to receive occupational therapy-led Early Stroke Specialist Vocational Rehabilitation&#x2005;+&#x2005;usual care. Questionnaire follow-up at 3, 6 and 12 months post randomisation. Mixed-methods process evaluation explored intervention experience, fidelity, compliance and implementation. Twenty-one NHS stroke services in England and Wales. Patients with new stroke within 12 weeks, aged &#x2265;&#x2005;18, in paid/unpaid work at stroke onset. People not intending to return to work excluded. Occupational therapists assessed stroke impact on participants and their job; co-ordinated NHS/employer/other stakeholders' support; negotiated job accommodations, monitored return to work and explored alternatives if return to work were unfeasible. Usual care involved NHS rehabilitation provided by community teams and medical follow-up. Primary outcome: self-reported return to work for &#x2265;&#x2005;2 hours/week 12 months post randomisation. Secondary outcomes: mood, functional ability, participation, productivity, work self-efficacy, health-related quality of life, confidence, mortality, carer strain, cost-consequences, COVID-19 impact. Between 1 June 2018 and 7 March 2022, 583 participants [mean age 54 years (standard deviation 11.1), 69.0% male, mean 29.9 days (standard deviation 20.0) post stroke, 452 (82.8%) ischaemic stroke] were randomised to Early Stroke Specialist Vocational Rehabilitation (n&#x2005;=&#x2005;324) or usual care (n&#x2005;=&#x2005;259). Primary and secondary outcome data were available for 454 (77.9%) and 316 (54.2%) participants, respectively. Intention-to-treat analysis showed no statistically significant difference in return to work between groups at 12 months [165/257 (64.2%) Early Stroke Specialist Vocational Rehabilitation vs. 117/197 (59.4%) usual-care, adjusted odds ratio 1.12 (95% confidence interval 0.8 to 1.87), p&#x2005;=&#x2005;0.3582]. Similar proportions of adverse events occurred in both groups [40/241 (16.6%) attended accident and emergency, 24/244 (9.1%) hospital admissions, 6/266 (2.3%) work accidents at 12 months]. Exploratory subgroup analyses indicated Early Stroke Specialist Vocational Rehabilitation potentially benefits older people (60+), and those with two or more post-stroke impairments. Health economic outcomes were consistent with primary clinical outcomes. Analysis using multiple imputation, adjusting for age, sex, utility or cost at baseline and site found Early Stroke Specialist Vocational Rehabilitation had higher costs [incremental cost &#xa3;1337 (95% confidence interval -1113 to 3787) and slightly more favourable incremental quality-adjusted life-years of 0.019 (95% confidence interval -0.012 to 0.051)]. Early Stroke Specialist Vocational Rehabilitation was valued by participants and service managers. In contrast, usual-care participants reported limited or no vocational rehabilitation and poor communication. Intervention compliance was achieved for 244 (75.3%) participants. Mentor support for occupational therapies appeared to increase fidelity. Most participants had mild-moderate stroke, unlike our feasibility evaluation which informed the sample size (powered to detect an absolute 13% difference in return to work). More people return to work than anticipated. There was significant loss to follow-up for primary, secondary and health economic outcomes. Employers proved difficult to recruit and engage. REturn To work After stroKE was unable to demonstrate an effect or cost effect of Early Stroke Specialist Vocational Rehabilitation on return to work 12 months post randomisation. The COVID-19 pandemic influenced employer behaviour, and remote working diluted Early Stroke Specialist Vocational Rehabilitation mechanisms in a predominantly mild-moderate sample, many of whom were able to self-navigate return to work. Research is needed to confirm Early Stroke Specialist Vocational Rehabilitation benefits in people marginalised by age or post-stroke impairment, and determine what interventions benefit younger stroke survivors. This synopsis presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number 15/130/11. Many people cannot REturn To work After stroKE and there is little National Health Service support for this. We developed early, stroke specialist vocational rehabilitation to support people to return to and remain in work. This was available for up to 1 year. We recruited working people aged 18 or over, within 12 weeks of new stroke and allocated at random, whether they received the new rehabilitation in addition to usual National Health Service care or usual National Health Service care only. Twelve months later we compared the potential benefits of the new rehabilitation to its costs in terms of how many in each group had returned to work. The trial recruited 583 stroke patients from 21 hospitals. Most people recruited had mild&#x2013;moderate stroke. Although 5% more people returned to work with the new rehabilitation, this difference was not statistically significant and might have happened by chance rather than because of the new rehabilitation. Overall, the new rehabilitation was found unlikely to offer the National Health Service value for money in the short term. Additional exploratory analysis suggested older people and those with more stroke disability might be more likely to benefit from the new rehabilitation. However, more research is needed to confirm these findings. The new rehabilitation was delivered as intended and valued by stroke survivors and National Health Service managers. Stroke survivors who received usual National Health Service care only, received little rehabilitation, which was poorly co-ordinated with limited or no vocational rehabilitation. The COVID-19 pandemic came at a critical point. It made flexible, home-based working the norm, particularly for managerial roles, reducing the effect of the new rehabilitation. People who sustain stroke with few lasting disabilities may be able to return to work without specialist support. However, further research is needed to confirm this and determine whether this applies to people of all ethnicities and job types.

National Institute for Health and Care Excellence technology appraisals assess the effectiveness and cost-effectiveness of medicines at a single point in the treatment pathway. However, for some disease areas, such as non-small cell lung cancer, there are many recommendations, making it difficult to use National Institute for Health and Care Excellence guidance. The treatment pathway for metastatic stage 4 non-small cell lung cancer can be divided into decision points (nodes) based on histology (squamous or non-squamous), programmed death-ligand 1 expression, presence of tumour mutations and line of therapy. The National Institute for Health and Care Excellence commissioned this pilot to assess the potential of taking a 'pathways approach' to technology appraisals. The aim was to build a single disease-specific cost-effectiveness model for metastatic stage 4 non-small cell lung cancer patients not eligible for targeted therapies at first line, that can be updated with economic and clinical data as required. We conducted a systematic review (searches last updated 11 July 2025) and network meta-analysis of treatment efficacy and safety at each decision node in the pathway. We used flexible fractional polynomial models for primary outcome progression-free survival, required for a model of treatment sequences. We built a novel cost-effectiveness model that compared sequences of treatments, and was populated using network meta-analyses for progression-free survival, data on overall survival after last-line therapy, evidence on treatment sequences from an analysis of systemic anticancer therapy data, and quality of life, cost and resource use estimates from previous technology appraisals. Drug list prices were used, but confidential discounts are available. We included 15 randomised controlled trials and 1 single-arm study in the review, judged as some concerns or low risk of bias. Immunotherapies, in combination with doublet platinum chemotherapy, were most effective first-line treatments, although with higher adverse event rates. Immunotherapy monotherapies were most effective at second line, unless patients were suitable for targeted therapies. Sequences starting with atezolizumab&#x2005;+&#x2005;bevacizumab&#x2005;+&#x2005;doublet platinum chemotherapy had similar costs and quality-adjusted life-years to sequences starting with pembrolizumab&#x2005;+&#x2005;doublet platinum chemotherapy. Sequences starting with pemetrexed&#x2005;+&#x2005;platinum chemotherapy had the lowest costs but also the lowest total quality-adjusted life-years. Sequences starting with pembrolizumab&#x2005;+&#x2005;doublet platinum chemotherapy had highest quality-adjusted life-years, but higher costs compared to other sequences. Sequences starting with pemetrexed&#x2005;+&#x2005;platinum chemotherapy had the lowest cost and the lowest number of quality-adjusted life-years. Sequences starting with pembrolizumab&#x2005;+&#x2005;doublet platinum chemotherapy had higher quality-adjusted life-years and higher costs than sequences starting with platinum chemotherapy. Sequences starting with atezolizumab had the highest predicted quality-adjusted life-year gains, slightly higher than for sequences starting with pembrolizumab. Sequences starting with platinum chemotherapy had the lowest quality-adjusted life-years, but the lowest total costs. Patients in the systemic anticancer therapy analysis had a shorter time on treatment than those in trials, resulting in lower treatment costs and causing the immunotherapy sequences to appear more cost effective. Our model can be used to estimate either the most cost-effective sequence of treatments or the most cost-effective treatment at a given point in the pathway, although our results are based on drug list prices and these would need to be updated to draw conclusions about the relative cost-effectiveness of different treatment sequences. We were able to use real-world data from systemic anticancer therapy to estimate model parameters and sequences that reflect clinical practice. Our model can readily be updated and used as a reference model for metastatic non-small cell lung cancer. The study is registered as PROSPERO CRD42023470119. This award was funded by the National Institute for Health and Care Research (NIHR) Evidence Synthesis programme (NIHR award ref: NIHR136097) and is published in full in Health Technology Assessment; Vol. 30, No. 46. See the NIHR Funding and Awards website for further award information. The National Institute for Health and Care Excellence helps doctors provide the best care to patients by deciding if new or existing medicines make a difference to patients. These decisions are made using an &#x2018;economic model&#x2019;, which helps the National Institute for Health and Care Excellence work out if treatments can help patients and are value for money for the NHS. For illnesses like lung cancer, patients will have a series of treatments, known as the treatment pathway. When the first treatment stops working, they move to a second treatment, and so on. Normally, when the National Institute for Health and Care Excellence looks at a new medicine, it is for one place in the treatment pathway, such as after the first medicine has stopped working. The National Institute for Health and Care Excellence repeats this work every time there is a new medicine to consider for the same pathway. There are now more than 50 recommendations for patients with the most common type of lung cancer, non-small cell lung cancer. This makes it difficult for doctors to be sure they choose the best care for each individual patient. We used data from clinical studies and national databases to develop a new &#x2018;economic model&#x2019; of the treatment pathway for patients with non-small cell lung cancer. This new analysis approach enabled us to compare both the effectiveness and the costs of different sequences of treatments for these patients, in a UK context. The treatment options for patients with non-small cell lung cancer can be divided into different &#x2018;decision points&#x2019;. These reflect whether the cancer has spread (cancer stage), whether the cancer cells have certain changes known as genetic &#x2018;mutations&#x2019;, and where patients are on the treatment pathway. We looked at advanced (stage 4) non-small cell lung cancer patients. Immunotherapies in combination with chemotherapy were most effective first treatment, but with more side effects than other treatments. Immunotherapies used alone were the most effective second treatment, unless patients had genetic &#x2018;mutations&#x2019; and were suitable for targeted therapies. The model could be used for future decisions on treatments for advanced non-small cell lung cancer patients.

People who inject drugs are disproportionately affected by hepatitis C virus. The emergence of direct-acting antiviral treatments for hepatitis C virus motivated England to achieve the World Health Organization's elimination target of decreasing hepatitis C virus incidence among people who inject drugs to <&#x2005;2 per 100 person-years (/100 person-years) by 2030. We determined whether existing testing and treatment strategies will reach this target in England, or whether improved strategies are needed and whether they are cost-effective. A dynamic hepatitis C virus transmission model among people who inject drugs was developed for four English regions. The model included the pathway from testing to treatment in prisons, drug treatment centres and other settings. Each pathway was parameterised using region-specific data, with yearly bio-behavioural surveys among people who inject drugs being used to parameterise and calibrate the model in a Bayesian framework. The model projected whether each region will reach the hepatitis C virus incidence target or what improvements (in testing and linkage to treatment) are needed from 2024 to achieve it. Hepatitis C virus care pathway costs were collated through interviews with practitioners and the published literature. The mean incremental cost-effectiveness ratio (per quality-adjusted life-year saved) was estimated for any 'improved' strategy that reached the incidence target compared to the baseline strategy. Incremental cost-effectiveness ratios were compared to a willingness-to-pay threshold of &#xa3;20,000/quality-adjusted life-year saved over a 50-year time horizon (3.5% annual discount rate). Across the four regions over 2016-22, an estimated 8831-9689 treatments occurred among 37,230 people who inject drugs, with the annual number treated increasing in prisons (7.8 times) and drug treatment centres (3.6 times). Model projections suggest that hepatitis C virus incidence among people who inject drugs has decreased across the regions by 56.1-85.4% (range of medians) over 2015-22, with incidence decreasing by 79.7-98.6% to 0.2-2.2/100 person-years by 2030. The World Health Organization incidence target (<&#x2005;2/100 person-years) will be reached with >&#x2005;80% probability in three regions and 40% probability in the other region. The probability of reaching the incidence target increases to >&#x2005;65% in this region if screening is increased in drug treatment centres (80% screened annually) or prisons (75% of people get tested during their prison stay), with these screening strategies being cost-effective. Numerous England regions may be on target to decrease hepatitis C virus incidence among people who inject drugs to <&#x2005;2/100 person-years. In regions that are not on target, further scale-up of testing in drug treatment centre or prison from 2024 could enable them to reach the World Health Organization elimination target and be cost-effective. Projections were based on model estimations, which need to be confirmed with empirical data. Data uncertainties affected our model projections, including uncertainty in the number of people who inject drugs in each region and the number of treatments given to people who inject drugs in different settings. Sample sizes for the yearly bio-behavioural surveys among people who inject drugs were small, and so samples were pooled over multiple years. Testing rates among people who inject drugs could not be directly estimated because the sentinel surveillance had incomplete coverage and could not identify people who inject drugs; testing rates were estimated through model calibration. There is interest in understanding what scale-back in testing can occur after 2030 without resulting in a rebound in hepatitis C virus incidence, and in developing models for each devolved nation to determine their progress to World Health Organization hepatitis C virus elimination targets. This synopsis presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number NIHR128513. Hepatitis C virus infection is a common cause of liver disease in England, with about 92,900 people infected. In the United Kingdom, most new hepatitis C virus infections result from injecting drug use. New treatments for hepatitis C virus can cure nearly all patients. The World Health Organization set targets for reducing the number of new hepatitis C virus infections among people who inject drugs by 2030. For England to meet these targets, the number of people who inject drugs that receive hepatitis C virus treatment needed to increase. New approaches to diagnose and refer people who inject drugs to treatment (called hepatitis C virus case-finding interventions) have been scaled up. These focus on locations where people who inject drugs can be tested, like prison and drug treatment services. We wanted to find out whether these new approaches have increased treatment enough to achieve the target for reducing new infections. If they have not, we wanted to find the cheapest way to improve hepatitis C virus case-finding to reach these targets. We developed a model that estimates how hepatitis C virus spreads among people who inject drugs in four English regions. We used this model to decide whether new approaches to improve hepatitis C virus case-finding will achieve the World Health Organization target in each region. If they will not, the model for each region was used to decide how to improve hepatitis C virus case-finding to reach the target. Managers of services and patients suggested how case-finding could be improved. We compared the healthcare costs and reduction in new hepatitis C virus infections to see if they were worthwhile improvements. We found that the new approaches to improve hepatitis C virus case-finding decreased the number of new hepatitis C virus infections enough in three English regions, but in the other region, more testing is needed in prisons or drug treatment services. The cost of this strategy was worthwhile, considering the number of new infections prevented. Many regions in England may be on target to reach the World Health Organization targets for decreasing new infections of hepatitis C virus. However, in some regions, more testing may be needed in prisons or drug treatment services to reach these World Health Organization targets. The cost of this is worthwhile because it is partially offset by reduced costs from fewer new infections.

Osteoporosis is a systemic skeletal disorder characterised by bone tissue deterioration, leading to reduced bone density and increased susceptibility to fractures. Osteoporosis screening is the process of identifying people with an increased risk of osteoporosis by using risk assessment tools or medical imaging. The National Institute for Health and Care Excellence recommends opportunistic risk assessment in women over 65 years or under 65 years with risk factors, though this guideline was last updated in 2017. Regular surveillance of the available evidence is warranted to gauge the volume and type of evidence published on key issues relating to population-based and targeted screening for osteoporosis. To identify and review the volume and type of evidence on effectiveness and cost-effectiveness of population-based and targeted osteoporosis screening in women and to explore the consideration of health equity in the evidence base. Two information specialists developed the search strategy in MEDLINE (via Ovid) and translated it to 10 other databases. The title and abstract then full text of each record were screened by two independent reviewers. Disagreements were resolved through discussion. Records found through supplementary searches were single-screened as were reference lists of relevant guidelines identified. One reviewer completed data extraction of included studies, with a second reviewer checking the accuracy. Included studies were required to be experimental designs, systematic reviews or cost-effectiveness studies with a standard care comparator. Populations of interest were women over 65 years and women below 65 years with osteoporosis risk factors. Any population or targeted screening intervention involving any combination of risk assessment and dual energy X-ray absorptiometry scan designed to identify women with, or at risk for, osteoporosis. Outcomes related to osteoporosis prevention (osteoporotic fractures, all-cause fractures and mortality), possible screening harms and cost-effectiveness. Searches were conducted in 11 databases and were supplemented by forward and backward citation searching. Study characteristics and equity considerations were tabulated and narratively described. The 19 included studies consisted of 3 randomised controlled trials with 9 sibling papers, 1 non-concurrent cohort study and 6 reviews. The primary studies generally included women 65 years old and older, with interventions involving several risk assessment and screening methods. Most reviews investigated the general population and included either bone mineral density measurement or clinical risk assessment for screening. Studies mainly reported fracture outcomes, with some quality-of-life and cost-effectiveness measures. Equity-relevant features analysed by studies included education, relationships, income and age. Our inclusion criteria may have excluded some evidence discussed by other related reviews. Evidence on the effectiveness and cost-effectiveness of osteoporosis screening is limited, with reviews mainly drawing conclusions from the same few primary studies currently available. The evidence base lacks consideration of equity-related characteristics. High-quality trial evidence is required, particularly for targeted screening. Equity characteristics should be addressed in future work. The review aims to identify gaps in the current evidence base for targeted and population osteoporosis screening to inform future research and healthcare policy-makers' decisions. This article presents independent research funded by the National Institute for Health and Care Research (NIHR) Evidence Synthesis programme as award number NIHR169162. Osteoporosis is a bone disease that causes bones to become weak and fragile. This can lead to fractures happening more easily. It is most common in women who have gone through the menopause (postmenopausal). We investigated the current evidence about screening for osteoporosis in postmenopausal women. There is currently no national screening programme for osteoporosis in the United Kingdom. We sought to answer the following questions: 1. (a) How much evidence is there that screening all women over 65 years for osteoporosis helps prevent fractures when compared to their usual care? 1. (b) How much evidence is there that screening women under 65 years with risk factors for osteoporosis helps prevent fractures when compared to their usual care? How much evidence is there on the cost-effectiveness of osteoporosis screening? How are health inequalities considered in research around osteoporosis screening? We sought opinions from a group of people who bring their carer, patient or public perspective to our research. Their input helps ensure that the research is relevant and accessible. We found 19 studies that fit our inclusion criteria, including 4 clinical studies and 6 reviews. The studies generally included all women aged 65 years and older and looked at different screening methods. Studies reported outcomes, including fractures, quality of life and cost-effectiveness of screening, and some considered health inequalities. There is a relatively small amount of evidence on the effectiveness and cost-effectiveness of osteoporosis screening, which mainly looks at all women over 65 years rather than women under 65 years with risk factors. Most of the available evidence does not consider the impact of health inequalities. More research, with a greater focus on health inequalities, is needed to help policymakers make decisions about screening.

Approximately 90,000 people in the United Kingdom have a long-term catheter. Use of long-term catheters is associated with common adverse events including blockage of the catheter and symptomatic catheter-associated urinary tract infection. Washout solutions are often used prophylactically to prevent these adverse events, but evidence for the benefits and potential harms is insufficient. Does the addition of weekly prophylactic washouts of the catheter to standard long-term catheter care improve the outcomes of adults with long-term catheter. A pragmatic three-arm multicentre open-label superiority randomised controlled trial with embedded qualitative study. Adults with long-term catheter in situ (any route or type) with no plans to discontinue long-term catheter use were recruited in a community setting in the United Kingdom. Participants received training to self-administer the washouts, with/without the assistance of a carer. Participants were randomised 1&#x2005;:&#x2005;1&#x2005;:&#x2005;1 to standard long-term catheter care plus weekly prophylactic saline washouts; weekly prophylactic acidic washouts; or no prophylactic washouts. The primary clinical and health economic outcomes were catheter blockage requiring intervention (/1000 catheter days) up to 24 months post randomisation and incremental cost per quality-adjusted life-year gained. Outcome data were patient reported. Eighty of the planned 600 participants were recruited (26 saline; 27 acidic; 27 control). There was a reduction in incidence of blockages requiring treatment (per 1000 catheter days) from 20.92 (control) to 9.96 (saline) and 10.53 (acidic). The incidence rate ratio favoured the washout groups [saline 0.65 (97.5% confidence interval 0.24 to 1.77); p&#x2005;=&#x2005;0.33 and acidic 0.59 (97.5% confidence interval 0.22 to 1.63); p&#x2005;=&#x2005;0.25] but was not statistically significant. There was a reduction in the secondary outcome of symptomatic catheter-associated urinary tract infection requiring antibiotic use (per 1000 catheter days) from 8.05 (control) to 3.71 (saline) and 6.72 (acidic). The incidence rate ratio favoured the washout groups [saline 0.40 (97.5% confidence interval 0.20 to 0.80); p&#x2005;=&#x2005;0.003 and acidic 0.98 (97.5% confidence interval 0.54 to 1.78); p = 0.93]; however, the significance should be interpreted cautiously given the small sample size. There were few adverse events. Quality-of-life outcomes were similar between groups. Due to the low sample size, the health economic outcomes could not be analysed. The embedded qualitative work demonstrated that the study design was feasible and acceptable to healthcare professionals and participants involved with the trial. Healthcare professionals perceived the training of participants to have minimal impact on healthcare resources and participants were empowered to self-manage the washouts and integrate it into their routine care. COVID-19 led to recruitment difficulties and early termination of the study by the funder. Sample size was not met. There is a suggestion that regular prophylactic washout use may result in the reduction of catheter blockage and symptomatic catheter-associated urinary tract infection. However, the results are inconclusive due to the small sample size. Participants found the washouts acceptable to use and could self-manage the washouts with training. The study design was acceptable to involved participants and healthcare workers. We recommend a multinational randomised controlled trial to produce evidence on the clinical effectiveness of long-term catheter washout policies. This synopsis presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number 17/30/02. Long-term catheters are used by approximately 90,000 people in the United Kingdom for various reasons. Common problems when using the long-term catheter are blockages of the catheter and urine infections which often require healthcare assistance and impact on quality of life. To help prevent these problems, current standard care involves changing the catheter every 12 weeks or so. Some people also flush the catheter regularly with washout solutions, but there is no good evidence to support this. The CATHETER II study evaluated if flushing the catheter regularly reduces the number of blockages, urine infections and other catheter problems. It also asked participants if the washouts were acceptable to use and improved their quality of life. We recruited adults with long-term catheter in the United Kingdom to take part. They were randomly allocated to (1) preventative washouts with saline, or (2) preventative washouts with citric acid, or (3) no preventative washouts. All participants continued standard long-term catheter care. Participants, or their carer, were trained to do the washouts and these were administered every week for up to 24 months. We contacted participants by telephone every month to ask about any problems with the catheter or washouts and asked them to complete a questionnaire about their quality of life every 6 months. We interviewed participants and healthcare professionals to better understand their experience in the study. The study ended early because it was difficult to recruit participants during the COVID-19 pandemic, with 80 of the planned 600 participants recruited. Therefore, the results are not conclusive but do suggest that regular preventative washouts might reduce the number of blockages of the catheter and urine infections. Participants and healthcare professionals who were interviewed said that people with long-term catheter can be trained to do the washouts effectively. Participants had a generally positive experience using the washouts. Further studies will be needed.

Proximal phalanx finger shaft fractures are common and can impair hand function. There is controversy, but no high-quality evidence, on how they are best treated. We compared the clinical and cost-effectiveness of surgery versus non-surgical splint treatment. The primary objective was to compare hand function following surgical fixation with hand function following non-surgical splint treatment using the Hand Health Profile of the Patient Evaluation Measure at 6 months post randomisation. Pragmatic multicentre, parallel superiority randomised (1&#x2005;:&#x2005;1) trial. Twenty-four acute hospitals in the United Kingdom National Health Service. Patients &#x2265;&#x2005;16 years with one or more proximal phalanx shaft fracture(s), which can be treated via either surgery or non-surgical splint treatment. Patients with intra-articular, base-metaphyseal, neck, open proximal phalanx fractures, injury &#x2265;&#xa0;14 days or unable to adhere to trial procedures/complete questionnaires were excluded. Surgery was any mode of surgical fixation that was considered as appropriate by the treating specialist. Non-surgical splint treatment consisted of any technique/material used in routine care, which may involve manipulation of the fracture with analgesia or local anaesthetic, and subsequent bracing through an externally applied support, usually performed in a clinic or therapy room environment. The primary outcome measure was the Hand Health Profile of the Patient Evaluation Measure (possible range 11-77, higher scores indicate worst function). Measurements were collected at 6 weeks, 3, 6 and 12 months; 6 months was the primary outcome time point. The primary health outcome for economic evaluation was quality-adjusted life-years in accordance with National Institute for Health and Care Excellence guidelines. Between 9 November 2020 and 2 February 2023, 113 participants were randomised to surgery (n&#x2005;=&#x2005;56) or non-surgical treatment (n&#x2005;=&#x2005;55); 2 were excluded. Participants were 60% male, with mean age of 38 years. Treatment arms were balanced. Fifty-three participants in the surgical and 46 in the non-surgical group were included in the primary analysis. At 6 months, the mean Patient Evaluation Measure was 27.1 (standard deviation&#x2005;=&#x2005;13.6, n&#x2005;=&#x2005;48) in the surgical group and 25 (standard deviation 12.4, n&#x2005;=&#x2005;41) in the non-surgical group, with no clinically important difference between groups (adjusted difference in means for surgery vs. non-surgical groups 3, 95% confidence interval&#xa0;-1.6 to 7.7). There were no differences at 6 weeks and 3 months. There were more complications in the surgery group. Surgery was more expensive, resulting in an incremental cost-effectiveness ratio of &#xa3;39,686 per quality-adjusted life-year, with a 3.2% probability of being cost-effective at the National Institute for Health and Care Excellence threshold of &#xa3;20,000. This study supports the conclusion that surgery does not restore better hand function than non-surgical treatment. Surgery results in additional complications and is more expensive. We were unable to further determine if surgery is worse than splint or if the two treatments are equivalent, because of slow recruitment and the smaller than the planned sample size. Research should be directed towards further comparisons of treatments for common hand fractures. This synopsis presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number NIHR127292. This study is about a common finger injury, a broken bone in the finger that has broken in the middle. This bone is one of the three bones in the finger and is the one at the base of the finger, closest to the palm, and is called a proximal phalanx shaft finger fracture. Proximal phalanx shaft fractures are treated with surgery or without surgery using finger supports, and we did not know which is best. National Health Service hand specialists, patients and researchers worked together to improve care by finding out which treatment is better for patients and represents value for money. We compared surgery using metalwork (pins, screws or plates) to fix the fracture with non-surgical treatment using supports (splints) applied to the finger in clinic, sometimes using pain killers or a local anaesthetic. One hundred and thirteen patients took part. The treatment each patient in the study received was decided randomly so that a fair and useful comparison of the treatments could be made. Patients completed questionnaires about how well they could use their hand and general health at 6 weeks, 3 months, 6 months (most important time) and 1 year; we also collected details about their treatments, finger movement, hand strength, recovery and any problems (complications). Though the study was not as big as we planned, we found that surgery was not better for proximal phalanx shaft fractures than finger splints. Surgery was more expensive for patients and the National Health Service. Good results can be achieved without the need for surgery in most cases, hence finger splints should be tried first. The injured finger will get better with treatment after this type of break but is unlikely to fully return to normal.

Rates of self-harm and suicide in prisoners in England and Wales are high, exceeding rates observed in the general population, of similar age and gender. Assessment, Care in Custody and Teamwork (ACCT) is the prison service's self-harm monitoring process. Closure of this process is a high-risk time where people may be at risk of self-harm. Mechanisms to manage risk, particularly following closure of the ACCT management process, mean that many people subsequently self-harm while not being monitored. This creates an opportunity to evaluate the examination of a new tool that could be used to assess ongoing risk after an incident of self-harm and closure of ACCT, and bridge ongoing support. To assess the acceptability of a new risk tool to clinicians, prison officers and people in custody, and subsequently, develop an operational implementation pathway to embed the risk tool in practice. A qualitative study using action learning groups. A total of five action learning groups were conducted in four male and one female prison sites. These included participation from six staff and eight people in custody. Four themes emerged from the thematic analysis, including establishing an effective implementation process, consistent administration and scoring, purposeful follow-up procedure, and meaningful engagement with people in custody. Two exemplar operational pathways were presented to identify how the risk tool could be incorporated into routine practice. Although this qualitative study used transparent and systematic methods, our sample size was small and may not be representative. Suicidal thoughts, behaviours and attempts in people in prison continue to be common, and there is a need for a structured approach to reduce repetition. Action learning methods identified barriers, potential solutions and how a new tool could work alongside existing risk management. Future research should focus on the development of the exemplar pathways. In the first instance, a stakeholder working group could review the tool to make initial refinements, followed by a wider implementation study to develop the processes of how the tool could work in practice. This article presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number 16/159/09. We know that the rates of self-harm and suicide in prisoners in England and Wales are high. This is a concern to health professionals and prison staff who support and manage those people in custody. Although the prison system in England and Wales supports people when they are feeling at risk, we know that when this support stops, people are more likely to harm themselves again. For this reason, our study is evaluating how a new tool developed in this project can help to support people in custody and staff to monitor people who might remain at risk after an incident of self-harm. This paper examines the different views of staff working in custody and people who are in custody (prisoners) to identify what they thought about the new tool. The discussions used a format referred to as an &#x2018;Action Learning Group&#x2019; to work out how the group could be used in practice. These groups followed a semistructured process, with the facilitator guiding the flow of discussion using a pre-defined topic guide to encourage reflection, while group members have the flexibility to explore the topic, consider barriers and determine their own solutions. The findings from talking to people working and incarcerated in custody identified four key areas to consider. The four key ideas or themes included the need to establish a straightforward pathway with a clear starting point, a consistent administration process and scoring system, reliable follow-up actions to ensure the safety of people at risk of further self-harm, and they explored how staff working in custody could develop a meaningful way of engaging with people in custody. The individuals who contributed to group discussion talked about possible ways of how best to incorporate the new tool into routine practice. We recommend that because we only talked to a small number of people that more research is needed to include the views of more people to inform implementation.

Diabetic retinopathy is a leading cause of visual loss. Hypothesis-generating data from cardiovascular outcome trials suggest that fenofibrate therapy may reduce the progression of diabetic retinopathy. To determine whether treatment with fenofibrate reduces the progression of diabetic retinopathy. We conducted a parallel-group, double-masked, placebo-controlled clinical trial of fenofibrate. A web-based algorithm allocated participants to treatment arms by minimisation. The trial was positioned within NHS Scotland's Diabetic Eye Screening Programme. Adults with diabetes and non-referable retinopathy or maculopathy (based on Diabetic Eye Screening retinal image grading) were eligible. Study treatment was mailed to participants' homes. Participants who were eligible at the screening assessment entered an active pre-randomisation run-in during which they took 145&#x2005;mg fenofibrate. After randomisation, participants received 145&#x2005;mg fenofibrate tablets or placebo. Study treatment was taken daily in those with normal renal function, or on alternate days in those with impaired renal function. The primary outcome was a composite of developing referable diabetic retinopathy or maculopathy, or requiring treatment for diabetic retinopathy or maculopathy. Incremental cost-effectiveness was assessed in terms of the primary outcome and per modelled quality-adjusted life-year gained. Data were obtained from 6-monthly interviews by research nurses and linkage to national healthcare data sets. Selected adverse events were adjudicated by study clinicians masked to treatment allocation. One thousand four hundred and eighty-four participants entered the pre-randomisation run-in, of whom 1151 were randomised. The primary outcome occurred in 131 (22.7%) of 576 participants assigned fenofibrate and 168 (29.2%) of 575 participants assigned placebo (hazard ratio 0.73; 95% confidence interval 0.58 to 0.91; p&#x2005;=&#x2005;0.006) over a median of 4.0 years. Any progression of retinopathy or maculopathy, and development of macular oedema were also reduced. There was no effect on visual function, quality of life, or visual acuity. Fenofibrate use resulted in a non-significant reduction in 6-monthly health service costs (mean difference -&#xa3;101, 95% confidence interval -&#xa3;243 to &#xa3;42), leading to dominance over standard care and a high probability of cost-effectiveness. Based on modelling (assuming no difference in background healthcare costs by treatment allocation), fenofibrate led to a small increase (&#xa3;6) in cost for a small gain (0.02) in quality-adjusted life-years; incremental cost-effectiveness ratio &#xa3;406 per quality-adjusted life-year gained. The probability of cost-effectiveness was 79-86% at thresholds of &#xa3;20,000-30,000 per quality-adjusted life-year gained. Early Treatment Diabetic Retinopathy Study retinopathy grading is considered the gold standard, but it is not used in large-scale retinal screening programmes; Diabetic Eye Screening grading is based on Early Treatment Diabetic Retinopathy Study but is less granular. Fenofibrate was clinically effective and cost-effective for reducing the progression of diabetic retinopathy compared with placebo among participants with early retinal changes. LENS participants will be followed for 10 years to assess the long-term effects of fenofibrate therapy. This synopsis presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number 14/49/84. Diabetes can affect the inner layer at the back of the eye, a condition called diabetic retinopathy. Many people need to see a National Health Service eye specialist or need treatment for diabetic eye disease. Each year, diabetic retinopathy leads to 1500 people being certified as blind in the United Kingdom. This makes it a leading cause of blindness in working age adults. Fenofibrate is a drug that is sometimes used to lower cholesterol. Two studies from the 2000s suggested that fenofibrate may lower the risk of diabetic eye disease getting worse. However, those results were not convincing enough to change how doctors treat their patients. We ran the Lowering Events in Non-proliferative retinopathy in Scotland study to find out if fenofibrate may be useful for treating people with diabetic eye disease. Lowering Events in Non-proliferative retinopathy in Scotland was a large clinical trial. We studied 1151 adults with early diabetic eye disease from across Scotland. Participants came to a research clinic at the start to check if they were eligible. Study treatment was sent to peoples&#x2019; homes by post. Half the people in the study took fenofibrate tablets. The other half took placebo (i.e. dummy) tablets. Nobody knew which treatment they were getting. Research nurses phoned them every 6 months over the next 4 years. The study team used information from these calls and from National Health Service records to find out what happened to participants. We found that the people taking fenofibrate had a lower chance of their diabetic eye disease getting worse compared to those taking placebo. Fewer people taking fenofibrate needed to see a National Health Service specialist, have treatment for eye disease or developed swelling at the back of the eyes (called macular oedema) compared to placebo. We now have better evidence about the positive effect fenofibrate in patients with early diabetic eye disease, and the potential for savings to the National Health Service.

The ability to predict whether patients with a new diagnosis of Crohn's disease will develop disabling disease is an unmet clinical need. Magnetic resonance enterography is a first-line investigation for Crohn's disease, but its role in prognostication is unknown. To improve prediction of disabling Crohn's disease within 5 years of diagnosis by developing and internally evaluating a multivariable prediction model comprising clinical predictors and adding magnetic resonance enterography scores (Magnetic resonance Enterography Global Score, Simplified Magnetic Resonance Index of Activity and L&#xe9;mann Index). To estimate the healthcare costs incurred within 5 years of Crohn's disease diagnosis and to explore factors driving costs. A multicentre diagnostic inception cohort. Nine National Health Service hospitals. Aged &#x2265;&#x2005;16 years with newly diagnosed Crohn's disease. Comparative predictive ability of prognostic models, including magnetic resonance enterography scores (Magnetic resonance Enterography Global Score, Simplified Magnetic Resonance Index of Activity and L&#xe9;mann Index) versus a model based on clinical predictors alone for the development of modified Beaugerie disabling Crohn's disease within 5 years of diagnosis. We censored development of modified Beaugerie disabling disease &#x2264;&#x2005;90 days from diagnosis, and utilised time-to-event models using Royston-Parmar flexible parametric models. Risk group definitions were prespecified; for risk group definition 1, the high-risk patients were the top 40% with the greatest predicted risk, and the high-risk patients had an absolute risk &#x2265;&#x2005;10% for risk group definition 2. The absolute risk cut-off was calculated by sorting patients by predicted risk and using the risk of the eighth (10% of 81) patient who developed modified Beaugerie disabling disease. We studied 194 patients, median age 29, interquartile range 22-44 years. Within 5 years from diagnosis, 42% (81/194) developed modified Beaugerie disabling disease. There was a univariable association between initial need for steroid therapy and developing modified Beaugerie disabling disease [hazard ratio 2.11 (95% confidence interval 1.36 to 3.26)]. Using risk group definition 1, the baseline clinical model had 49% (95% confidence interval 39 to 60) sensitivity and 66% (95% confidence interval 57 to 74) specificity for predicting the development of modified Beaugerie disabling disease. There was no difference in sensitivity and specificity between models incorporating Magnetic resonance Enterography Global Score, Simplified Magnetic Resonance Index of Activity and L&#xe9;mann Index compared to the baseline clinical model. Using risk group definition 2, the model, including magnetic resonance enterography predictors, had 86% (95% confidence interval 77 to 92) sensitivity and 35% (95% confidence interval 27 to 45) specificity for predicting the development of modified Beaugerie disabling disease. There was no difference in sensitivity between the clinical model and models incorporating Magnetic resonance Enterography Global Score, Simplified Magnetic Resonance Index of Activity and L&#xe9;mann Index, but specificity was significantly lower for models incorporating Magnetic resonance Enterography Global Score [29% (95% confidence interval 22 to 38)] and L&#xe9;mann Index [29% (95% confidence interval 22 to 38)]. The mean total 5-year per-patient cost of health care was &#xa3;24,267 (standard deviation &#xa3;33,108). Mean 5-year costs were &#xa3;29,763 (standard deviation &#xa3;38,278) compared to &#xa3;20,327 (standard deviation &#xa3;28,368) for those with and without disabling disease, respectively. The largest contributor to costs was biologic use. Age under 40 years, presence of perianal disease and presence of severe endoscopic disease were associated with higher costs. Li&#xe8;ge and Montreal criteria for disabling disease could not be studied due to an insufficient event rate. Addition of magnetic resonance enterography scores to a multivariable model comprising existing clinical predictors did not improve prediction of modified Beaugerie disabling disease. Healthcare costs were increased in those aged under 40 years and patients with perianal and severe endoscopic disease. Testing the predictive ability of magnetic resonance enterography against alternative definitions for disabling Crohn's disease. This trial is registered as ISRCTN76899103. This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 15/59/17) and is published in full in Health Technology Assessment; Vol. 30, No. 18. See the NIHR Funding and Awards website for further award information. Crohn&#x2019;s disease is a chronic lifelong inflammatory bowel condition. Patients can have mild disease, but others develop &#x2018;disabling&#x2019; disease, which often requires treatment with powerful medication and bowel surgery. At the time of diagnosis, there are currently no reliable ways to predict if a patient will have mild or disabling disease in the future, although some factors, such as young patient age and smoking, are associated with worse outcomes. Knowing which patients are most likely to develop disabling Crohn&#x2019;s disease would be very useful because they could be considered for medication earlier to try and prevent this. Typical medications include biologic drugs, which suppress the immune system. Magnetic resonance enterography is a bowel imaging test often performed at diagnosis which demonstrates the extent of bowel involvement, how much inflammation is present and if there are complications, such as abscesses or bowel narrowing. Using statistical modelling, we investigated whether adding detailed analysis of magnetic resonance enterography images to standard predictors, such as age and smoking, could improve the prediction of future disabling disease within 5 years. We also estimated the healthcare costs incurred within 5 years of a new diagnosis of Crohn&#x2019;s disease. We studied 194 newly diagnosed patients from 9 NHS hospitals, of whom 42% (81/194) developed disabling disease. Magnetic resonance enterography did not improve our predictive ability compared to standard clinical factors. In a hypothetical group of 1000 patients, we would predict 418 to develop disabling disease, of whom we would correctly predict 206 patients but incorrectly identify 212 patients who would actually not develop disabling disease. The average cost per patient over 5 years was &#xa3;24,267 (&#xa3;29,763 for those developing disabling disease and &#xa3;20,327 for those who did not). The largest contributor to costs was biologic drugs. Magnetic resonance enterography remains vital for diagnosing and monitoring Crohn&#x2019;s disease but does not improve prediction of which patients will develop disabling disease.