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.

To systematically review evidence of the clinical effectiveness of psychosocial interventions for adults with substance use disorder that have a co-occurring common mental health disorder or borderline personality disorder. To identify papers that estimate the cost-effectiveness of interventions for patients with substance use disorder and common mental health disorder or borderline personality disorder. An umbrella review (a systematic review of systematic reviews) for clinical effectiveness was conducted. Systematic database searches [MEDLINE, EMBASE, PsycInfo® (American Psychological Association, Washington, DC, USA), Cochrane Database of Systematic Reviews, and Web of Science] were carried out in February 2024. Inclusion criteria: Adults with substance use disorder and common mental health disorder or borderline personality disorder; psychosocial interventions (with or without pharmacological therapies); comparators psychosocial treatments, treatment as usual, waitlist/no treatment; systematic reviews of randomised controlled trials. Data, including critical appraisal, were extracted into a standardised form by one reviewer, and checked by another. Data were discussed in a narrative review. A literature review of MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, and EconLit were undertaken to identify cost-effectiveness papers. An illustrative model was constructed to show how cost-effectiveness could be calculated if data were available. Of 5420 unique records, 30 systematic reviews were included in the clinical review. The methodological quality of the reviews was generally good. Most of the interventions and many of the active comparators studied resulted in some improvement for patients. Most reviews focused on depression, anxiety or post-traumatic stress disorder; there were some looking at mixed common mental health disorder or borderline personality disorder. There was much heterogeneity both between reviews, and between the randomised controlled trials within the reviews. The results suggested integrated treatment for co-occurring diagnosis patients may be better for common mental health disorder outcomes than treatment as usual of parallel uncoordinated services. One study was identified that met the cost-effectiveness criteria. However, this reported results alongside a clinical study and was not a modelling paper. The illustrative model should aid future researchers. Heterogeneity made it difficult to reach an overall conclusion about which therapies were best. Most reviews stated the results were not generalisable across all populations or settings. There were few reviews of borderline personality disorder; or of common mental health disorder other than anxiety/depression/post-traumatic stress disorder. Future research comparing integrated with parallel or sequential treatment, with follow-up of 6 months or longer, and sample size large enough to encompass dropout, may be beneficial. No implications for current practice could be recommended due to heterogeneity of reviews/randomised controlled trials within reviews. This study is registered as PROSPERO CRD42024515813. This award was funded by the National Institute for Health and Care Research (NIHR) Evidence Synthesis programme (NIHR award ref: NIHR166951) and is published in full in Health Technology Assessment; Vol. 30, No. 49. See the NIHR Funding and Awards website for further award information. People with substance use disorders (alcohol or drug) can have a co-occurring (comorbid) mental health disorder. The National Institute for Health and Care Excellence has produced guidance on treating people with co-occurring substance use and serious mental health disorder; however, this does not cover people with less severe mental health difficulties. This project aimed to identify evidence on the effectiveness (how well treatments worked) of psychosocial interventions (talking therapies or services designed to reduce substance use and lessen the symptoms of mental health disorders) for adults with substance use disorders and co-occurring common mental health disorders or borderline personality disorder. Therapies or services relevant to UK practice were investigated. Systematic literature reviews of randomised controlled trials (studies comparing two or more treatments allocated randomly) were sought. This project included 30 reviews of clinical effectiveness. Most reviews investigated depression, anxiety or post-traumatic stress disorder. Most therapies studied improved mental health and reduced substance use; as did some of the comparators (treatment as usual). The trials included in the reviews differed in the people treated, therapies, and the way outcomes of substance use, or mental health, were assessed. This made it difficult to draw conclusions about which therapies were best. Treating both substance use and mental health using a co-ordinated approach to co-occurring disorders (integrated treatment) was usually better than treating one condition alone, and sometimes better than two separate (parallel) treatments at the same time. There was limited evidence looking at treating one condition then the other (sequential), but evidence suggested it was similarly effective to integrated treatment. There was not much research on whether these treatments are cost-effective (good value for money). However, an example was developed to show how the cost-effectiveness of a promising therapy could be estimated.

NHS Talking Therapies for anxiety and depression is a service that provides people in England with psychological support. There are several referral routes into the service, digital front door technologies being the most recent addition. The aim of this National Institute for Health and Care Excellence early value assessment was to map available evidence, assess potential benefits and costs of NHS Talking Therapies referral pathways with and without digital front door technologies, and identify evidence gaps to help direct future data collection and further research. The External Assessment Group carried out a systematic literature review (December 2024) to gather evidence relating to Limbic Access (Limbic), Wysa Digital Referral Assistant (Wysa), Censeo Digital (Psyomics) and AskFirst (Sensely). Information was collected across four broad outcome categories: accuracy and acceptability, resource and system impact, patient-reported outcomes, and costs. All study types were eligible for inclusion in the systematic literature review, along with evidence provided by the manufacturers of digital front door technologies (via requests for information). In addition, the External Assessment Group interviewed and sent questionnaires to stakeholders, including National Institute for Health and Care Excellence Specialist Committee Members, and carried out exploratory analyses of costs and benefits. Evidence was only available for two digital front door technologies: Limbic Access and Wysa Digital Referral Assistant. Literature meeting the systematic literature review eligibility criteria comprised two published peer-reviewed studies, six unpublished studies and five requests for information responses. The strongest evidence related to accessibility and overall satisfaction with Limbic Access. Results from one peer-reviewed study showed that Limbic Access increased the number of referrals to NHS Talking Therapies versus services that did not implement the technology (odds ratio&#x2005;=&#x2005;1.10, 95% confidence interval 1.075 to 1.131); this included an increase in access for some minority groups [Asian (odds ratio&#x2005;=&#x2005;1.29; confidence interval 1.163 to 1.422), Black (odds ratio&#x2005;=&#x2005;1.35, confidence interval 1.183 to 1.551) and non-binary (odds ratio&#x2005;=&#x2005;2.95; confidence interval 2.065 to 4.206)]. Overall satisfaction reported by users who completed the Limbic Access referral process was high (&#x2265;&#x2005;89%). Resource impact evidence was provided by one peer-reviewed study; results showed that Limbic Access reduced clinical assessment duration by 12.7 minutes. No relevant information on quality and accuracy was identified. Respondents were positive about digital front door technologies, suggesting that these tools could lead to better quality and more accurate (1) pre-referral practices and (2) initial clinical assessments; however, experts were unable to clearly define quality or accuracy. The External Assessment Group's exploratory economic analysis results suggested that the amount of clinical assessment time required to notionally offset the Limbic Access or Wysa Digital Referral Assistant licence cost was small (<&#x2005;3 minutes). Most published evidence was non-comparative. The strength of the evidence provided by the technology companies was difficult to assess due to limited detail. Further evidence is required to better understand the benefits and costs of digital front door technologies for NHS Talking Therapies. Evidence generation should focus on whether digital front door technologies improve the accuracy and quality of clinical assessments and their impact on resources throughout the referral pathway. This study is registered as PROSPERO CRD42025634844. This award was funded by the National Institute for Health and Care Research (NIHR) Evidence Synthesis Programme (NIHR award ref: NIHR171847) and is published in full in Health Technology Assessment; Vol. 30, No. 52. See the NIHR Funding and Awards website for further award information. NHS Talking Therapies provide psychological support to people in England who have anxiety and depression. There are different ways to access these services, and one of the newest methods is by using digital front door technologies. Digital front door technologies are digital tools that gather relevant information (with or without the use of artificial intelligence); they are intended to make the NHS referral process quicker and more efficient. This research explored the potential benefits and costs of using digital front door technologies. An independent research team reviewed published and unpublished evidence, collected information from the companies that created the technologies, and interviewed experts. Robust evidence was lacking for the impact of digital front door technologies on four key outcomes: quality and accuracy of the data collected using digital front door technologies, accuracy of the clinical assessment, impact on administrative burden and time taken to review data collected by digital front door technologies. There was some evidence about the effectiveness of two digital front door technologies (Limbic Access and Wysa Digital Referral Assistant). The Limbic Access evidence was more robust than the Wysa Digital Referral Assistant evidence, particularly in terms of accessibility outcomes; Talking Therapies services that used Limbic Access experienced a larger increase in the number of referrals than services that did not implement Limbic Access. Digital front door technologies were associated with high levels of user satisfaction and may help save time during the initial clinical assessment. None of the evidence reported any harms associated with the adoption of the Limbic Access and the Wysa Digital Referral Assistant digital front door technologies. The adoption of digital front door technologies may provide value for money for the NHS. For the technologies to be considered to provide value for money, <&#x2005;3 minutes of clinical assessment time need to be saved or the technologies need to provide a very small gain in patient quality of life. Experts were generally positive about using digital front door technologies and felt the technologies could improve the quality and accuracy of referrals to NHS Talking Therapies. However, the experts could not clearly define what &#x2018;quality&#x2019; and &#x2018;accuracy&#x2019; meant in clinical practice. Overall, while findings are positive, more research is needed to fully understand the benefits, costs and impact of using digital front door technologies to access NHS Talking Therapies.

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&#x2005;:&#x2005;1) pilot cluster-randomised trial (N&#x2005;=&#x2005;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&#x2019; 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&#x2019;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&#x2019;s beliefs. Our intervention: could identify people&#x2019;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&#x2019;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.

Predicting a diagnosis of pre-eclampsia is based on a combination of clinical assessment of blood pressure, presence of protein in the urine, symptoms and laboratory test abnormalities. Accurately detecting pre-eclampsia is important to avoid false-positive diagnoses which could lead to unnecessary antenatal admissions and/or preterm delivery. Four blood tests that measure the biomarkers of placental growth factor or the ratio of soluble fms-like tyrosine kinase-1 to placental growth factor are available (known as Triage, Elecsys, DELFIA Xpress, and BRAHMS Kryptor tests). Abnormal measurements of these biomarkers can be used as an aid to predict a diagnosis of pre-eclampsia and maternal and fetal outcomes. To evaluate the test accuracy, clinical effectiveness and cost-effectiveness of placental growth factor -based tests used in conjunction with standard clinical assessment for predicting pre-eclampsia and maternal and fetal outcomes in pregnant women who are referred to secondary care with suspected pre-eclampsia in weeks 20-37 of pregnancy. A systematic review of the diagnostic/prognostic accuracy and clinical effectiveness of placental growth factor-based tests with standard clinical assessment. Database included MEDical Literature Analysis and Retrieval System, Excerpta Medica dataBASE and Cochrane Library. Other sources searched included relevant conference proceedings and websites, grey literature and research in progress. The most recent date of searching was 18 March 2021. An independent economic analysis was conducted using a decision tree model. The model includes short-term costs and quality-adjusted life-years for the management of women, maternal and neonatal outcomes and long-term outcomes for severe neonatal complications. The model compared the use of the test alongside standard clinical assessment to standard clinical assessment only. Two different estimates of standard clinical assessment were included, from the INSPIRE study and from National Institute of Health and Care Excellence Diagnostic Guidance 23. Seventeen studies were included in the systematic review. Two large, randomised trials provided the best available evidence to inform the economic model: The PARROT trial (Triage test) and the INSPIRE trial (Elecsys test). When used as rule-out tests for pre-eclampsia (with neonatal outcomes included), all four tests produced higher quality-adjusted life-years and higher costs than both types of standard clinical assessment. The incremental cost per quality-adjusted life-year ranged from &#xa3;637 (DELFIA test vs. standard clinical assessment from INSPIRE) to &#xa3;47,393 (Triage test vs. standard clinical assessment from diagnostics guidance 23) per quality-adjusted life-year. Incremental costs and quality-adjusted life-years were always very small, with incremental costs always less than the cost of the test and incremental quality-adjusted life-years always <&#x2005;0.006. Although the evidence for placental growth factor-based tests is advancing, there remains uncertainty for key parameters, such as diagnostic sensitivity and specificity. This particularly affects the Elecsys test. Despite uncertainties from lack of data, and heterogeneity across studies, the use of placental growth factor-based tests to rule out and rule in pre-eclampsia has the potential to provide improved outcomes at reduced cost when compared with standard clinical assessment. Future research priorities include more rigorous evaluation of the DELFIA and BRAHMS placental growth factor-based tests, more evidence for Triage and Elecsys as rule-in tests, and greater focus on Black, and Asian and Mixed ethnicity groups. This study is registered as PROSPERO CRD42020227085. This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: NIHR132386) and is published in full in Health Technology Assessment; Vol. 30, No. 54. See the NIHR Funding and Awards website for further award information. Pre-eclampsia is a condition that affects some pregnant women and, if not detected or left untreated, can cause serious health complications for the mother and/or the baby. Four tests are now available (Triage, Elecsys, BRAHMS and DELFIA) that can detect abnormal levels of certain proteins in the blood indicating that a pregnant woman may have pre-eclampsia. We investigated the use of these tests in addition to the usual tests done by doctors to diagnose pre-eclampsia. Results of the tests determine whether someone with suspected pre-eclampsia should be admitted to hospital or can be safely monitored as outpatients. We carried out expert medical evidence searches to update our knowledge of the accuracy and cost of these tests and to find out if the tests can help doctors correctly recommend the best form of treatment for each woman. make the best decisions or impact on delivery-related outcomes for mother and baby. We developed an economic computer model that estimated costs of treatment and benefits to the mother and baby, to predict whether the tests would be good value for money for the NHS. Economic modelling shows that placental growth factor-based tests are cost-effective compared with standard clinical assessment when used to help diagnose (rule in) or exclude (rule out) preterm pre&#x2011;eclampsia. Cost-effectiveness reflects the amount of money the NHS is willing to pay for health gain. These tests would be useful to help plan safe care and a safe birth for women with pre-eclampsia, and also to identify those unlikely to develop pre-eclampsia, and therefore reduce unnecessary hospitalisation. The tests may work differently in people who are pregnant with more than one baby. There is uncertainty about how effective two of the tests are (the BRAHMS and DELFIA tests) due to lack of research, and on the usefulness and costs of testing women more than once if the previous test was negative but they still have symptoms of pre-eclampsia.

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&#x2005;=&#x2005;8) and patients who had experienced ovarian hyperstimulation syndrome (n&#x2005;=&#x2005;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&#x2019; opinions varied on whether they would like to monitor their own symptoms at home &#x2013; 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.

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.

Our aim was to develop and evaluate the electronic frailty index+, a prognostic tool, including four integrated prognostic-decision models, to stratify older people into subgroups for targeting key interventions. Prognostic model development, internal validation and external validation using large data sets and longitudinal cohort study data, with decision curve and health economic analysis. Patients aged 65+ years. The 12-month outcomes for prognostic models: new home care package care home admission emergency department attendance/hospitalisation with fall/fracture all-cause mortality. We developed and internally validated models for our key outcomes in one large data set. We used internal-external cross-validation for the home care model and full external validation for the remaining three models in a second large data set. We used CARE75+ to investigate additional predictive value of clinical measures practical for primary care. We translated the prognostic models into a framework to support clinical decision-making. We integrated the falls prediction models with effect size estimates from network meta-analysis to examine potential cost savings. We used data from 660,417 patients in SAIL, 88,947 in Connected Bradford and 252 CARE75+ participants. Model performance was promising in internal-external cross-validation, with average calibration slope 1.00 (95% confidence interval 0.99 to 1.01), average calibration-in-the-large -0.01 (95% confidence interval -0.02 to 0.01), average observed/expected ratio 0.99 (95% confidence interval 0.98 to 1.01) and average C-statistic 0.81 (95% confidence interval 0.81 to 0.81). Model performance was promising on internal and external validation, although with some evidence for overprediction of falls risk, with calibration slope 1.25 (95% confidence interval 1.24 to 1.27), calibration-in-the-large -0.931 (95% confidence interval -0.938 to -0.920), observed/expected ratio 0.43 (95% confidence interval 0.42 to 0.44), C-statistic 0.83 (0.82 to 0.83). Model performance was promising on internal validation, but it showed some miscalibration on external validation, with calibration slope 0.75 (95% CI 0.74 to 0.76), calibration-in-the-large -1.60 (-1.62 to -1.58) and observed/expected ratio 0.25 (95% CI 0.24 to 0.25), C-statistic of 0.86 (95% CI 0.86 to 0.86). The model showed excellent performance across the full range of predicted risks on external validation, with average calibration slope 1.00 (0.98 to 1.01), average calibration-in-the-large -0.23 (-0.27 to -0.19), average observed/expected ratio 0.77 (0.75 to 0.79) and average C-statistic 0.83 (0.82 to 0.83). Modelling indicated that provision of multifactorial assessment and treatment for people with an annual falls risk of &#x2265;&#xa0;40% has the largest cost reduction per targeted person (&#xa3;1025). All four prediction models have promising predictive performance, although some had evidence of overprediction of risk (miscalibration). Decision curve analysis indicates potential clinical utility, and economic modelling provides novel information for policy-makers and commissioners. Future research should include model impact studies to evaluate use of the models in routine care. We were unable to complete external validation of the home care prediction model. This study is registered as ClinicalTrials.gov ID NCT04113174. This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 127905) and is published in full in Health Technology Assessment; Vol. 30, No. 61. See the NIHR Funding and Awards website for further award information. Some text in this summary is reproduced from Clegg A. Development and Evaluation of the Electronic Frailty Index+ (eFI+) Tool: Integrated Prognostic-decision Modelling to Target Interventions for Older People With Moderate or Severe Frailty. University of Leeds; 2020. URL: https://lida.leeds.ac.uk/development-and-evaluation-of-the-electronic-frailty-index-efi-tool-integrated-prognostic-decision-modelling-to-target-interventions-for-older-people-with-moderate-or-severe-frailty/. Frailty is common in older age. It develops because, as we get older, our bodies change, and can lose their inbuilt reserves, for example we lose muscle strength. These changes mean that older people with frailty can experience sudden, dramatic changes in their health as a result of seemingly small problems, such as infection or new medication. This means that they can be at risk of losing their independence, falling, being admitted to a nursing home or dying. In this study, we used anonymised information from two very large databases to develop four &#x2018;risk prediction tools&#x2019; that predict, in the next 12 months, which older people are at risk of: needing new or increased home care services hospital admission with a fall or fracture (serious falls) nursing home admission dying. We then used a separate database to see if simple tests, like measuring walking speed or grip strength, can help us identify people with frailty at risk of serious falls. The final step was to test whether offering treatments to prevent serious falls is likely to offer value for money &#x2013; important information for the NHS and social care. All four risk prediction tools have promising performance and thus can help identify people likely to experience the four outcomes over the next 12 months. However, there were some limitations, particularly relating to the tool to identify people at risk of nursing home admission. Also, the addition of walking speed and grip strength measures did not make a notable improvement to the falls prediction tool. We found that the greatest cost saving for individuals was if falls&#x2019; prevention interventions were provided to people at higher risk of serious falls (over 40% risk of falling in next 12 months). Through our work, we expect to have a positive impact on the health and well-being of older people living with frailty, their families and carers along with major benefits to the NHS and social care.

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.

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.

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.

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.

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.

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.

Sleep disturbances are common and distressing for people with dementia and their family carers and can lead to carers having interrupted sleep, low mood and care breakdown. Medication can have harmful side effects and is generally ineffective. Non-pharmacological interventions should be first-line treatments, yet until now there have not been effective treatments. To establish whether Dementia RElAted Manual for Sleep; STrAtegies for RelaTives (DREAMS START), a multicomponent intervention, reduced sleep disturbance in people with dementia living at home at 8 months compared with National Health Service treatment (treatment as usual). We conducted a two-arm, multicentre, parallel-arm, superiority randomised controlled trial with masked outcome assessment. Participants were randomised (1&#x2005;:&#x2005;1 ratio) to DREAMS START intervention plus treatment as usual or treatment as usual alone. Analyses were intention to treat. We conducted a mixed-method process evaluation with additional substudies: one exploring how United Kingdom-based South Asians experience sleep disturbance and dementia, and one exploring the interaction of sleep, dementia and long-term conditions. We recruited dyads of people with dementia and sleep disturbance living at home and family carers from 12 National Health Service trusts and the Join Dementia Research service in England. DREAMS START is a six-session, multicomponent, manualised intervention delivered to family carers of people with dementia who implement strategies to improve their relatives' sleep. It is delivered face to face or remotely by non-clinically trained graduates weekly or fortnightly and incorporates information about sleep and dementia, promotes de-arousal at night, adaptive stimulus control (e.g. bedtime routine maintenance), daytime behavioural activation, increasing access to light, improving carer sleep and making a tailored action plan. The primary outcome was sleep disturbance measured using the Sleep Disorders Inventory at 8 months. Between February 2021 and March 2023, 377 dyads were randomly assigned, 189 to treatment as usual and 188 to DREAMS START plus treatment as usual. Mean age of participants with dementia was 79.4 years (standard deviation 9.0), and 206 (55%) were women. Mean Sleep Disorders Inventory score at 8 months was lower in the intervention versus treatment-as-usual arm [15.16 (standard deviation 12.77), n&#x2005;=&#x2005;159, vs. 20.34 (16.67), n&#x2005;=&#x2005;163]; adjusted difference in means [-4.70 (95% confidence interval -7.65 to -1.74); p&#x2005;=&#x2005;0.002]. Seventeen (9%) people with dementia in the intervention and 17 (9%) in the control arm died during the trial; deaths were unrelated to the intervention. The mean incremental difference in health and care costs incorporating wider costs was &#xa3;116 less per dyad (95% confidence interval -&#xa3;5769 to &#xa3;5536) for DREAMS START compared to treatment as usual. There was a 78% probability that DREAMS START is cost-effective compared to treatment as usual at a &#xa3;20,000 decision threshold with no significant difference in quality of life. DREAMS START plus treatment as usual is clinically effective in reducing sleep disturbance in people living at home with dementia at 8 months, demonstrating sustained effectiveness beyond intervention delivery. DREAMS START is likely to be cost-effective, and delivery by non-clinically trained graduates increases potential for National Health Service implementation at scale. We relied upon family carers' proxy and self-reported outcomes, with intervention participants potentially more invested and optimistic, increasing risk of bias. Additionally, based on our feasibility randomised controlled trial, we did not include actigraphy or another direct measure of sleep and activity. Studies should explore the longer-term effect of DREAMS START (we are following up participants at 2 years), and there should be an implementation study considering delivery and scaling up DREAMS START in real-world healthcare settings. This synopsis presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number NIHR128761. Many people with dementia have disturbed sleep, which is distressing for them and their family, yet there are no proven safe and effective treatments. To address this gap, we developed Dementia RElAted Manual for Sleep; STrAtegies for RelaTives, a six-session intervention. People without clinical training deliver Dementia RElAted Manual for Sleep; STrAtegies for RelaTives individually to family carers. It uses strategies like increasing light, activity, comfort, routine and relaxation; adapted for each person. We wanted to know: &#x2018;Do people with dementia living at home sleep better 8 months after receiving Dementia RElAted Manual for Sleep; STrAtegies for RelaTives compared to people who did not receive it?&#x2019; We also wanted to see if it is good value and how it works. We tested Dementia RElAted Manual for Sleep; STrAtegies for RelaTives in a trial across 12 English National Health Service sites. Between February 2021 and March 2023, 377 pairs of people with dementia and family carers took part. Half were offered Dementia RElAted Manual for Sleep; STrAtegies for RelaTives plus usual care and half just usual care. We asked about the person with dementia and carers&#x2019; sleep, their quality of life and carer mood at the start and after 4 and 8 months. We measured costs of Dementia RElAted Manual for Sleep; STrAtegies for RelaTives and compared services used between the groups. People with dementia whose carers received Dementia RElAted Manual for Sleep; STrAtegies for RelaTives alongside usual care had better sleep than those who just had usual care after 8 months. We found that family carers who had Dementia RElAted Manual for Sleep; STrAtegies for RelaTives reported better sleep and less anxiety than those who did not. Health and care services used by people with dementia and carers receiving Dementia RElAted Manual for Sleep; STrAtegies for RelaTives cost &#xa3;116 less per person than those who just had usual care. Dementia RElAted Manual for Sleep; STrAtegies for RelaTives is a safe and effective treatment of sleep in dementia; it benefits family carers with potential to save money.

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.

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.