Health technology assessment最新文献

{"title":"High-flow nasal cannula therapy versus continuous positive airway pressure for non-invasive respiratory support in paediatric critical care: the FIRST-ABC RCTs.","authors":"Padmanabhan Ramnarayan, Alvin Richards-Belle, Karen Thomas, Laura Drikite, Zia Sadique, Silvia Moler Zapata, Robert Darnell, Carly Au, Peter J Davis, Izabella Orzechowska, Julie Lester, Kevin Morris, Millie Parke, Mark Peters, Sam Peters, Michelle Saull, Lyvonne Tume, Richard G Feltbower, Richard Grieve, Paul R Mouncey, David Harrison, Kathryn Rowan","doi":"10.3310/PDBG1495","DOIUrl":"https://doi.org/10.3310/PDBG1495","url":null,"abstract":"<p><strong>Background: </strong>Despite the increasing use of non-invasive respiratory support in paediatric intensive care units, there are no large randomised controlled trials comparing two commonly used non-invasive respiratory support modes, continuous positive airway pressure and high-flow nasal cannula therapy.</p><p><strong>Objective: </strong>To evaluate the non-inferiority of high-flow nasal cannula, compared with continuous positive airway pressure, when used as the first-line mode of non-invasive respiratory support in acutely ill children and following extubation, on time to liberation from respiratory support, defined as the start of a 48-hour period during which the child was free of respiratory support (non-invasive and invasive).</p><p><strong>Design: </strong>A master protocol comprising two pragmatic, multicentre, parallel-group, non-inferiority randomised controlled trials (step-up and step-down) with shared infrastructure, including internal pilot and integrated health economic evaluation.</p><p><strong>Setting: </strong>Twenty-five National Health Service paediatric critical care units (paediatric intensive care units and/or high-dependency units) across England, Wales and Scotland.</p><p><strong>Participants: </strong>Critically ill children assessed by the treating clinician to require non-invasive respiratory support for (1) acute illness (step-up randomised controlled trial) or (2) within 72 hours of extubation (step-down randomised controlled trial).</p><p><strong>Interventions: </strong>High-flow nasal cannula delivered at a flow rate based on patient weight (Intervention) compared to continuous positive airway pressure of 7-8 cm H<sub>2</sub>O pressure (Control).</p><p><strong>Main outcome measures: </strong>The primary clinical outcome was time to liberation from respiratory support. The primary cost-effectiveness outcome was 180-day incremental net monetary benefit. Secondary outcomes included mortality at paediatric intensive care unit/high-dependency unit discharge, day 60 and day 180; (re)intubation rate at 48 hours; duration of paediatric intensive care unit/high-dependency unit and hospital stay; patient comfort; sedation use; parental stress; and health-related quality of life at 180 days.</p><p><strong>Results: </strong>In the step-up randomised controlled trial, out of 600 children randomised, 573 were included in the primary analysis (median age 9 months). Median time to liberation was 52.9 hours for high-flow nasal cannula (95% confidence interval 46.0 to 60.9 hours) and 47.9 hours (95% confidence interval 40.5 to 55.7 hours) for continuous positive airway pressure (adjusted hazard ratio 1.03, one-sided 97.5% confidence interval 0.86 to ∞). The high-flow nasal cannula group had lower use of sedation (27.7% vs. 37%) and mean duration of acute hospital stay (13.8 days vs. 19.5 days). In the step-down randomised controlled trial, of the 600 children randomised, 553 were included in the primary analysis (media","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":"29 9","pages":"1-96"},"PeriodicalIF":3.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12067162/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144011767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mortality impact, risks, and benefits of general population screening for ovarian cancer: the UKCTOCS randomised controlled trial.","authors":"Usha Menon, Aleksandra Gentry-Maharaj, Matthew Burnell, Andy Ryan, Jatinderpal K Kalsi, Naveena Singh, Anne Dawnay, Lesley Fallowfield, Alistair J McGuire, Stuart Campbell, Steven J Skates, Mahesh Parmar, Ian J Jacobs","doi":"10.3310/BHBR5832","DOIUrl":"10.3310/BHBR5832","url":null,"abstract":"<p><strong>Background: </strong>Ovarian and tubal cancers are lethal gynaecological cancers, with over 50% of the patients diagnosed at advanced stage.</p><p><strong>Trial design: </strong>Randomised controlled trial involving 27 primary care trusts adjacent to 13 trial centres based at NHS Trusts in England, Wales and Northern Ireland.</p><p><strong>Methods: </strong>Postmenopausal average-risk women, aged 50-74, with intact ovaries and no previous ovarian or current non-ovarian cancer.</p><p><strong>Interventions: </strong>One of two annual screening strategies: (1) multimodal screening (MMS) using a longitudinal CA125 algorithm with repeat CA125 testing and transvaginal scan (TVS) as second line test (2) ultrasound screening (USS) using TVS alone with repeat scan to confirm any abnormality. The control (C) group had no screening. Follow-up was through linkage to national registries, postal follow-up questionnaires and direct communication with trial centres and participants.</p><p><strong>Objective: </strong>To assess comprehensively risks and benefits of ovarian cancer screening in the general population.</p><p><strong>Outcome: </strong>Primary outcome was death due to ovarian or tubal cancer as assigned by an independent outcomes review committee. Secondary outcomes included incidence and stage at diagnosis of ovarian and tubal cancer, compliance, performance characteristics, harms and cost-effectiveness of the two screening strategies and a bioresource for future research.</p><p><strong>Randomisation: </strong>The trial management system confirmed eligibility and randomly allocated participants using computer-generated random numbers to MMS, USS and C groups in a 1:1:2 ratio.</p><p><strong>Blinding: </strong>Investigators and participants were unblinded and outcomes review committee was masked to randomisation group.</p><p><strong>Analyses: </strong>Primary analyses were by intention to screen, comparing separately MMS and USS with C using the Versatile test.</p><p><strong>Results: </strong>1,243,282 women were invited and 205,090 attended for recruitment between April 2001 and September 2005.</p><p><strong>Randomised: </strong>202,638 women: 50,640 MMS, 50,639 USS and 101,359 C group.</p><p><strong>Numbers analysed for primary outcome: </strong>202,562 (>99.9%): 50,625 (>99.9%) MMS, 50,623 (>99.9%) USS, and 101,314 (>99.9%) C group.</p><p><strong>Outcome: </strong>Women in MMS and USS groups underwent 345,570 and 327,775 annual screens between randomisation and 31 December 2011. At median follow-up of 16.3 (IQR 15.1-17.3) years, 2055 women developed ovarian or tubal cancer: 522 (1.0% of 50,625) MMS, 517 (1.0% of 50,623) USS, and 1016 (1.0% of 101314) in C group. Compared to the C group, in the MMS group, the incidence of Stage I/II disease was 39.2% (95% CI 16.1 to 66.9) higher and stage III/IV 10.2% (95% CI -21.3 to 2.4) lower. There was no difference in stage in the USS group. 1206 women died of the disease: 296 (0.6%) MMS, 291 (0.6%) US","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":" ","pages":"1-93"},"PeriodicalIF":3.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10542866/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9455506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effectiveness of biomarker-guided duration of antibiotic treatment in children hospitalised with confirmed or suspected bacterial infection: the BATCH RCT.","authors":"Cherry-Ann Waldron, Philip Pallmann, Simon Schoenbuchner, Debbie Harris, Lucy Brookes-Howell, Céu Mateus, Jolanta Bernatoniene, Katrina Cathie, Saul N Faust, Josie Henley, Lucy Hinds, Kerry Hood, Chao Huang, Sarah Jones, Sarah Kotecha, Sarah Milosevic, Helen Nabwera, Sanjay Patel, Stéphane Paulus, Colin Ve Powell, Jenny Preston, Huasheng Xiang, Emma Thomas-Jones, Enitan D Carrol","doi":"10.3310/MBVA3675","DOIUrl":"https://doi.org/10.3310/MBVA3675","url":null,"abstract":"<p><strong>Background: </strong>Procalcitonin is a biomarker specific for bacterial infection, with a more rapid response than other commonly used biomarkers, such as C-reactive protein, but it is not routinely used in the National Health Service.</p><p><strong>Objective: </strong>To determine if using a procalcitonin-guided algorithm may safely reduce duration of antibiotic therapy compared to standard of care in hospitalised children with suspected or confirmed infection.</p><p><strong>Design: </strong>A pragmatic, multicentre, open-label, parallel two-arm, individually randomised controlled trial with internal pilot phase, qualitative study and health economic evaluations.</p><p><strong>Setting: </strong>Paediatric wards or paediatric intensive care units within children's hospitals (<i>n</i> = 6) and district general hospitals (<i>n</i> = 9) in the United Kingdom.</p><p><strong>Participants: </strong>Children aged between 72 hours and 18 years admitted to hospital and being treated with intravenous antibiotics for suspected or confirmed bacterial infection.</p><p><strong>Interventions: </strong>Procalcitonin-guided algorithm versus usual standard care alone.</p><p><strong>Main outcome measures: </strong>Coprimary outcomes were duration of intravenous antibiotic use and a composite safety measure.</p><p><strong>Results: </strong>Between 11 June 2018 and 12 October 2022, 1949 children were recruited: 977 to the procalcitonin group [427 female (43.7%), 550 male (56.3%)], and 972 to the usual care group [478 female (49.2%), 494 male (50.8%)]. Duration of intravenous antibiotics was not significantly different between the procalcitonin group (median 96.0 hours) and the usual care group (median 99.7 hours) [hazard ratio = 0.96 (0.87, 1.05)], and the procalcitonin-guided algorithm was non-inferior to usual care [risk difference = -0.81% (95% confidence interval upper bound 1.11%)]. At clinical review, a procalcitonin result was available for 81.8% of the time, which was considered as part of clinical decision-making 66.6% of the time, and the algorithm was adhered to 57.2% of the time. Incremental cost-effectiveness ratio per duration of intravenous antibiotics hour avoided from bootstrapped samples was £467.62 per intravenous antibiotic hour avoided. Cost analysis of complete cases was also higher in the procalcitonin arm for all age groups, and for children aged 5 years and over. The intervention is not cost-effective as it is more expensive with no significant improvement in intravenous antibiotic duration.</p><p><strong>Limitations: </strong>Robust antimicrobial stewardship programmes were already implemented in the lead recruiting sites, and adherence to the algorithm was poor. Clinicians may be reluctant to adhere to biomarker-guided algorithms, due to unfamiliarity with interpreting the test result.</p><p><strong>Conclusions: </strong>In children hospitalised with confirmed or suspected bacterial infection, the addition of a procalcitonin-gui","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":"29 16","pages":"1-125"},"PeriodicalIF":3.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144093427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A network approach to addressing the needs of patients with incurable head and neck cancer and their families.","authors":"Joanne M Patterson, Catriona R Mayland, Peter Bath, Michelle Lawton, Valerie Bryant, David Hamilton, Madina Hasan, Tony Stone, Richard Campbell, Annabel Crum, Linda Sharp","doi":"10.3310/TKLD6486","DOIUrl":"https://doi.org/10.3310/TKLD6486","url":null,"abstract":"<p><strong>Background: </strong>Patients with incurable head and neck cancer have considerable unmet needs and complex symptom burden, with evidence of substantial geographical and/or socioeconomic inequalities. Accurate information on healthcare needs, resource utilisation and service provision in the last year of life is lacking. This places limits on service delivery planning and the development and testing of interventions to better meet needs. Our partnership spans three regions, which nationally have some of the highest rates of incurable head and neck cancer.</p><p><strong>Aims: </strong>The overall aims were to (1) establish a palliative head and neck cancer partnership, (2) identify and evaluate routine incurable head and neck cancer data sources and utilise these to develop and address research priorities.</p><p><strong>Objectives: </strong>O1. Develop a palliative head and neck cancer network within the North of England, representing a geographical area with high incidence of incurable head and neck cancer and palliative care needs. O2. Develop and refine research questions and priorities. O3. Engage with data providers to identify relevant data sets and specific data fields to understand the potential quality and utility of these to inform research priorities.</p><p><strong>Methods: </strong>There were three interconnected work packages: WP1: A 'snowballing' approach to establish a network of clinicians, researchers, patient and public representatives, data architects and key stakeholders with an interest in head and neck cancer palliative care. WP2: A Delphi consensus process to develop and refine research questions and priorities, based on national guidance and systematic reviews of evidence gaps. WP3: Identification of national and local data sets and exploration of the potential data quality and utility, and associated information governance processes for access.</p><p><strong>Results: </strong>WP1: A diverse network was established, encompassing members from a wide range of professions and patient/carer groups. WP2: The Delphi consisted of two rounds involving up to 66 participants. Consensus was reached on 12 research questions representing 4 key areas of prioritisation: service provision, symptom management, psychosocial support and information provision and communication. WP3: A range of national and local data sources were identified as having the potential to address the research priorities. A directory of data sources was developed. Working in an iterative way, data sets and relevant data fields were mapped to the 12 potential research priority areas to assess the applicability of using routine data to address these priorities.</p><p><strong>Limitations: </strong>Approximately, one-third of participants in the Delphi process dropped out in round 2. Despite attempts to be flexible in our approach, retaining participants, particularly for patients and their families on a palliative care pathway, is challenging.</p><p><strong>","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":" ","pages":"1-29"},"PeriodicalIF":3.5,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12067161/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144008744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lessons from the PROTECT-CH COVID-19 platform trial in care homes.","authors":"Philip M Bath, Jonathan Ball, Matthew Boyd, Heather Gage, Matthew Glover, Maureen Godfrey, Bruce Guthrie, Jonathan Hewitt, Robert Howard, Thomas Jaki, Edmund Juszczak, Daniel Lasserson, Paul Leighton, Val Leyland, Wei Shen Lim, Pip Logan, Garry Meakin, Alan Montgomery, Reuben Ogollah, Peter Passmore, Philip Quinlan, Caroline Rick, Simon Royal, Susan D Shenkin, Clare Upton, Adam L Gordon","doi":"10.3310/MTRS8833","DOIUrl":"https://doi.org/10.3310/MTRS8833","url":null,"abstract":"<p><strong>Background: </strong>Coronavirus disease-2019 was associated with significant mortality and morbidity in care homes in 2020-1. Repurposed antiviral drugs might reduce morbidity and mortality through reducing viral transmission, infection, replication and inflammation. We aimed to compare the safety and efficacy of potential antiviral drugs in care home residents.</p><p><strong>Methods: </strong>We designed a cluster-randomised, open-label, blinded end-point platform trial to test drugs in a postexposure prophylaxis paradigm. Participants aged 65+ years from United Kingdom care homes, with or without nursing, were eligible for participation. Care homes were to be allocated at random by computer to administer 42 days of antiviral agent (ciclesonide or niclosamide) plus standard care versus standard care alone to residents. The primary outcome at 60 days after randomisation comprised the most serious outcome, which was defined as all-cause mortality, all-cause hospitalisation, severe acute respiratory syndrome coronavirus 2 infection or no infection. Analysis would be by intention to treat using ordinal logistic regression. Other outcomes included individual components of the primary outcome, transmission, plus health economic and process evaluation outcomes. The planned sample size was 300 care homes corresponding to 9600 residents. With ~40% of care homes predicted to develop an outbreak during the trial, we needed to recruit 750 homes/24,000 residents.</p><p><strong>Results: </strong>We initiated the trial including protocol, approvals, insurance, website, database, data algorithms, intervention selection and training materials. We built a network of principal investigators and staff (91) and care homes (299) to support the trial. However, we never contracted care homes or general practitioners since the trial was stopped in September 2021, as vaccination in care homes had significantly reduced infections. Multiple delays significantly delayed the start date, such as: (1) reduced prioritisation of pandemic trials in 2021; (2) cumbersome mechanisms for choosing the investigational medicinal products; (3) contracting between National Institute for Health and Care Research and the investigational medicinal product manufacturers; (4) publicising the investigational medicinal products; (5) identification of sufficient numbers of care homes; (6) identification and contracting with several thousand general practitioners; (7) limited research nurse availability and (8) identification of adequate insurance to cover care homes for research. Generic challenges included working across the four home nations with their different structures and regulations.</p><p><strong>Limitations: </strong>The feasibility of contracting between the sponsor and the principal investigators, general practitioners and care homes; screening, consent and treatment of care home residents; data acquisition and the potential benefit of postexposure prophylaxis were never t","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":" ","pages":"1-26"},"PeriodicalIF":3.5,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12010236/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143990492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A personalised health intervention to maintain independence in older people with mild frailty: a process evaluation within the HomeHealth RCT.","authors":"Rachael Frost, Yolanda Barrado-Martín, Louise Marston, Shengning Pan, Jessica Catchpole, Tasmin Rookes, Sarah Gibson, Jane Hopkins, Farah Mahmood, Benjamin Gardner, Rebecca L Gould, Claire Jowett, Rashmi Kumar, Rekha Elaswarapu, Christina Avgerinou, Paul Chadwick, Kalpa Kharicha, Vari M Drennan, Kate Walters","doi":"10.3310/MBCV1794","DOIUrl":"10.3310/MBCV1794","url":null,"abstract":"<p><strong>Background: </strong>Frailty is common in later life and can lead to adverse health outcomes. Services aimed at preventing decline in early stages of frailty may support older people to remain independent for longer. We developed and tested a new service, HomeHealth, in a randomised controlled trial. HomeHealth was a multidomain behaviour change service based in the voluntary sector in England targeting mobility, socialising, nutrition and psychological well-being.</p><p><strong>Objective: </strong>To describe the population reach, fidelity, acceptability, context and mechanisms of impact of the HomeHealth service.</p><p><strong>Design and methods: </strong>Mixed-methods process evaluation of a randomised trial.</p><p><strong>Setting and participants: </strong>HomeHealth trial participants (older people aged 65+ years with mild frailty) and service providers.</p><p><strong>Data sources and analysis: </strong>Population reach was evaluated through comparison to local census data. Fidelity of audio-recorded appointments was assessed by two independent raters using a structured checklist. Using data from appointments attended, types of goals set and progress towards goals, we described appointment characteristics, goals and signposting, and evaluated three mechanisms of impact: (1) effect of appointment attendance on independence, (2) effect of goal progress on independence and (3) whether selecting a particular goal type led to improvements in the corresponding intermediate outcome. We thematically analysed qualitative interviews with 49 older people, 7 HomeHealth workers and 8 stakeholders to explore acceptability and context.</p><p><strong>Results: </strong>HomeHealth participants were similar with regards to deprivation, education and housing status to the local older population but with lower rates of minority ethnic groups. HomeHealth was delivered with good fidelity (81.7%) in voluntary sector organisations. Appointments were well attended (mean 5.33 out of the 6 intended), but attendance was not associated with better independence scores at 12 months [mean difference 1.29 (-8.20 to 10.78)]. Participants varied in progress towards goals within appointments (mean progress 1.15/2.00), but greater goal progress was not associated with improved independence scores at 12 months [mean difference -0.40 (-2.38 to 1.58)]. Mobility goals were most frequently selected (49%), but type of goal had no impact on independence and little impact on intermediate outcomes. Forty-one per cent were signposted or referred to other supportive services, with ongoing support where needed throughout this process. Qualitative data indicated that HomeHealth was acceptable, empowering for those who saw a need for change and fitted well within host voluntary sector organisations.</p><p><strong>Limitations: </strong>Census data were only available for all adults aged over 65 in local areas rather than a mildly frail population, who are likely to be older, female ","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":" ","pages":"1-23"},"PeriodicalIF":3.5,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11995243/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143788267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-VEGF drugs compared with laser photocoagulation for the treatment of proliferative diabetic retinopathy: a systematic review and individual participant data meta-analysis.","authors":"Mark Simmonds, Alexis Llewellyn, Ruth Walker, Helen Fulbright, Matthew Walton, Rob Hodgson, Laura Bojke, Lesley Stewart, Sofia Dias, Thomas Rush, João Pereira Figueira, Sobha Sivaprasad, John G Lawrenson, Tunde Peto, David Steel","doi":"10.3310/MJYP6578","DOIUrl":"10.3310/MJYP6578","url":null,"abstract":"<p><strong>Background: </strong>Proliferative diabetic retinopathy is a major cause of sight loss in people with diabetes, with a high risk of vitreous haemorrhage, tractional retinal detachment and other complications. Panretinal photocoagulation is the primary established treatment for proliferative diabetic retinopathy. Anti-vascular endothelial growth factor drugs are used to treat various eye conditions and may be beneficial for people with proliferative diabetic retinopathy.</p><p><strong>Objective: </strong>To investigate the efficacy and safety of anti-vascular endothelial growth factor therapy for the treatment of proliferative diabetic retinopathy when compared to panretinal photocoagulation.</p><p><strong>Methods: </strong>A systematic review and network meta-analysis of randomised controlled trials comparing anti-vascular endothelial growth factor (alone or in combination) to panretinal photocoagulation in people with proliferative diabetic retinopathy. The database searches were updated in May 2023. Trials where the primary focus was treatment of macular oedema or vitreous haemorrhage were excluded. Key outcomes were best corrected visual acuity, diabetic macular oedema and vitreous haemorrhage. Individual participant data were obtained and analysed for three large, high-quality trials in combination with published data from other trials. Network meta-analyses of best corrected visual acuity and meta-analyses of other outcomes combined individual participant data with published data from other trials; regression analyses against patient covariates used just the individual participant data.</p><p><strong>Results: </strong>Twelve trials were included: one of aflibercept, five of bevacizumab and six of ranibizumab. Individual participant data were available from 1 aflibercept and 2 ranibizumab trials, representing 624 patients (33% of the total). When considered together, anti-vascular endothelial growth factors produced a modest, but not clinically meaningful, benefit over panretinal photocoagulation in best corrected visual acuity, after 1 year of follow-up (mean difference in logarithm of the minimum angle of resolution -0.116, 95% credible interval -0.183 to -0.038). There was no clear evidence of a difference in effectiveness between the anti-vascular endothelial growth factors. The benefit of anti-vascular endothelial growth factor appears to decline over time. Analysis of the individual participant data trials suggested that anti-vascular endothelial growth factor therapy may be more effective in people with poorer visual acuity, in those who have vitreous haemorrhage and, possibly, in people with poorer vision generally. Anti-vascular endothelial growth factor was superior to panretinal photocoagulation at preventing macular oedema after 1 year (relative risk 0.48, 95% confidence interval 0.28 to 0.83) and possibly at preventing vitreous haemorrhage (relative risk 0.72, 95% confidence interval 0.47 to 1.10). Anti-vascular endoth","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":" ","pages":"1-75"},"PeriodicalIF":3.5,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11995242/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143788268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of prognostic models to improve prediction of metastasis in patients following potentially curative treatment for primary colorectal cancer: the PROSPECT trial.","authors":"Vicky Goh, Susan Mallett, Manuel Rodriguez-Justo, Victor Boulter, Rob Glynne-Jones, Saif Khan, Sarah Lessels, Dominic Patel, Davide Prezzi, Stuart Taylor, Steve Halligan","doi":"10.3310/BTMT7049","DOIUrl":"https://doi.org/10.3310/BTMT7049","url":null,"abstract":"<p><strong>Background: </strong>Despite apparently curative treatment, many patients with colorectal cancer develop subsequent metastatic disease. Current prognostic models are criticised because they are based on standard staging and omit novel biomarkers. Improved prognostication is an unmet need.</p><p><strong>Objectives: </strong>To improve prognostication for colorectal cancer by developing a baseline multivariable model of standard clinicopathological predictors, and to then improve prediction via addition of promising novel imaging, genetic and immunohistochemical biomarkers.</p><p><strong>Design: </strong>Prospective multicentre cohort.</p><p><strong>Setting: </strong>Thirteen National Health Service hospitals.</p><p><strong>Participants: </strong>Consecutive adult patients with colorectal cancer.</p><p><strong>Interventions: </strong>Collection of prespecified standard clinicopathological variables and more novel imaging, genetic and immunohistochemical biomarkers, followed by 3-year follow-up to identify postoperative metastasis.</p><p><strong>Main outcome: </strong>Best multivariable prognostic model including perfusion computed tomography compared with tumour/node staging. Secondary outcomes: Additive benefit of perfusion computed tomography and other biomarkers to best baseline model comprising standard clinicopathological predictors; measurement variability between local and central review; biological relationships between perfusion computed tomography and pathology variables.</p><p><strong>Results: </strong>Between 2011 and 2016, 448 participants were recruited; 122 (27%) were withdrawn, leaving 326 (226 male, 100 female; mean ± standard deviation 66 ± 10.7 years); 183 (56%) had rectal cancer. Most cancers were locally advanced [≥ T3 stage, 227 (70%)]; 151 (46%) were node-positive (≥ N1 stage); 306 (94%) had surgery; 79 (24%) had neoadjuvant therapy. The resection margin was positive in 15 (5%); 93 (28%) had venous invasion; 125 (38%) had postoperative adjuvant chemotherapy; 81 (25%, 57 male) developed recurrent disease. Prediction of recurrent disease by the baseline clinicopathological time-to-event Weibull multivariable model (age, sex, tumour/node stage, tumour size and location, treatment, venous invasion) was superior to tumour/node staging: sensitivity: 0.57 (95% confidence interval 0.45 to 0.68), specificity 0.74 (95% confidence interval 0.68 to 0.79) versus sensitivity 0.56 (95% confidence interval 0.44 to 0.67), specificity 0.58 (95% confidence interval 0.51 to 0.64), respectively. Addition of perfusion computed tomography variables did not improve prediction significantly: <i>c</i>-statistic: 0.77 (95% confidence interval 0.71 to 0.83) versus 0.76 (95% confidence interval 0.70 to 0.82). Perfusion computed tomography parameters did not differ significantly between patients with and without recurrence (e.g. mean ± standard deviation blood flow of 60.3 ± 24.2 vs. 61.7 ± 34.2 ml/minute/100 ml). Furthermore, baseline model pr","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":"29 8","pages":"1-91"},"PeriodicalIF":3.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12010235/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144003180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stopping anticoagulation for isolated or incidental subsegmental pulmonary embolism: the challenges and lessons from the STOPAPE RCT.","authors":"Daniel Lasserson, Pooja Gaddu, Samir Mehta, Agnieszka Ignatowicz, Sheila Greenfield, Clare Prince, Carole Cummins, Graham Robinson, Jonathan Rodrigues, Simon Noble, Susan Jowett, Mark Toshner, Michael Newnham, Alice Turner","doi":"10.3310/UGHF6892","DOIUrl":"https://doi.org/10.3310/UGHF6892","url":null,"abstract":"<p><strong>Background: </strong>The increasing use of computed tomography pulmonary angiography to investigate patients with suspected pulmonary embolism has led to an increase in diagnosis of small subsegmental pulmonary embolism, which is rarely detectable with nuclear medicine-based imaging, the standard imaging modality prior to the development of computed tomography pulmonary angiography. The case fatality of pulmonary embolism has fallen in line with the increase in subsegmental pulmonary embolism diagnoses from computed tomography pulmonary angiography suggesting that we may be over-diagnosing pulmonary embolism (i.e. we may be diagnosing mild forms of pulmonary embolism which may not need any treatment). Given that full anticoagulation has significant side effects of bleeding and subsegmental pulmonary embolism was not commonly diagnosed previously with nuclear medicine imaging (and therefore left predominantly untreated prior to computed tomography pulmonary angiography scanning), there is growing equipoise about the value of full anticoagulation for patients with subsegmental pulmonary embolism.</p><p><strong>Methods: </strong>We tried to undertake an open randomised trial with blinded end-point adjudication that recruited patients diagnosed with subsegmental pulmonary embolism without evidence of thrombus in the leg veins, termed 'isolated subsegmental pulmonary embolism'. We allocated patients with isolated subsegmental pulmonary embolism to either continuing with at least 3 months of full-dose anticoagulation (standard care) or stopping anticoagulation completely, unless they had a temporary hospital admission where prophylactic (i.e. preventative doses) of anticoagulation is standard practice. In addition, we interviewed patients and clinicians about their views on stopping anticoagulation for isolated subsegmental pulmonary embolism which would be a substantial change from current practice. We planned to assess the accuracy of isolated subsegmental pulmonary embolism diagnoses from computed tomography pulmonary angiographies.</p><p><strong>Results: </strong>The trial was stopped prematurely due to low recruitment. This was due to a combination of insufficient trial sites, problems with identifying patients who were suitable to be recruited at the time of acute assessment in hospital, the impact of COVID-19 on research infrastructure and a lower prevalence than had been predicted based on published studies. Our interview study showed that the intervention (i.e. changing practice to stopping treatment) is feasible, although there were concerns raised about safety, which a trial would be needed to address. We did not have sufficient trial participants to determine accuracy of initial isolated subsegmental pulmonary embolism diagnoses.</p><p><strong>Conclusion: </strong>Although we were not able to answer the question of whether it is clinically effective and cost-effective to stop anticoagulating patients with isolated subsegmental pu","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":"29 11","pages":"1-12"},"PeriodicalIF":3.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12010252/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144019691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Supporting self-management with an internet intervention for low back pain in primary care: a RCT (SupportBack 2).","authors":"Adam W A Geraghty, Taeko Becque, Lisa C Roberts, Jonathan Hill, Nadine E Foster, Lucy Yardley, Beth Stuart, David A Turner, Gareth Griffiths, Frances Webley, Lorraine Durcan, Alannah Morgan, Stephanie Hughes, Sarah Bathers, Stephanie Butler-Walley, Simon Wathall, Gemma Mansell, Malcolm White, Firoza Davies, Paul Little","doi":"10.3310/GDPS2418","DOIUrl":"https://doi.org/10.3310/GDPS2418","url":null,"abstract":"<p><strong>Background: </strong>Low back pain is highly prevalent and a leading cause of disability. Internet-delivered interventions may provide rapid and scalable support for behavioural self-management. There is a need to determine the effectiveness of highly accessible, internet-delivered support for self-management of low back pain.</p><p><strong>Objective: </strong>To determine the clinical and cost-effectiveness of an accessible internet intervention, with and without physiotherapist telephone support, on low back pain-related disability.</p><p><strong>Design: </strong>A multicentre, pragmatic, three parallel-arm randomised controlled trial with parallel economic evaluation.</p><p><strong>Setting: </strong>Participants were recruited from 179 United Kingdom primary care practices.</p><p><strong>Participants: </strong>Participants had current low back pain without indicators of serious spinal pathology.</p><p><strong>Interventions: </strong>Participants were block randomised by a computer algorithm (stratified by severity and centre) to one of three trial arms: (1) usual care, (2) usual care + internet intervention and (3) usual care + internet intervention + telephone support. 'SupportBack' was an accessible internet intervention. A physiotherapist telephone support protocol was integrated with the internet programme, creating a combined intervention with three brief calls from a physiotherapist.</p><p><strong>Outcomes: </strong>The primary outcome was low back pain-related disability over 12 months using the Roland-Morris Disability Questionnaire with measures at 6 weeks, 3, 6 and 12 months. Analyses used repeated measures over 12 months, were by intention to treat and used 97.5% confidence intervals. The economic evaluation estimated costs and effects from the National Health Service perspective. A cost-utility study was conducted using quality-adjusted life-years estimated from the EuroQol-5 Dimensions, five-level version. A cost-effectiveness study estimated cost per point improvement in the Roland-Morris Disability Questionnaire. Costs were estimated using data from general practice patient records. Researchers involved in data collection and statistical analysis were blind to group allocation.</p><p><strong>Results: </strong>Eight hundred and twenty-five participants were randomised (274 to usual primary care, 275 to usual care + internet intervention and 276 to the physiotherapist-supported arm). Follow-up rates were 83% at 6 weeks, 72% at 3 months, 70% at 6 months and 79% at 12 months. For the primary analysis, 736 participants were analysed (249 usual care, 245 internet intervention, 242 telephone support). There was a small reduction in the Roland-Morris Disability Questionnaire over 12 months compared to usual care following the internet intervention without physiotherapist support (adjusted mean difference of -0.5, 97.5% confidence interval -1.2 to 0.2; <i>p</i> = 0.085) and the internet intervention with physiotherapist suppor","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":"29 7","pages":"1-90"},"PeriodicalIF":3.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12010237/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143965512","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}