Health technology assessment最新文献

{"title":"Melatonin versus midazolam in the premedication of anxious children attending for elective surgery under general anaesthesia: the MAGIC non-inferiority RCT.","authors":"Christopher Deery, Robert Bolt, Diana Papaioannou, Matthew Wilson, Marie Hyslop, Esther Herbert, Nikki Totton, Zoe Marshman, Tracey Young, Jennifer Kettle, Sondos Albadri, Simon Atkins, Katie Biggs, Janet Clarkson, Chris Evans, Laura Flight, Jacqui Gath, Fiona Gilchrist, Kate Hutchence, Nicholas Ireland, Amanda Loban, Amy Norrington, Hamish Paton, Jaydip Ray, Helen Rodd, Elena Sheldon, Richard Simmonds, Christopher Vernazza","doi":"10.3310/CWKF1987","DOIUrl":"10.3310/CWKF1987","url":null,"abstract":"<p><strong>Background: </strong>Anxiety in children prior to general anaesthesia is common, with up to half displaying distress. Anxiety and distress may lead to unsuccessful anaesthesia, together with greater postoperative pain, agitation and behavioural changes after surgery including sleep disturbances. Midazolam is the current standard premedication; however, it has adverse effects such as the potential for respiratory suppression and unpredictable effects which may result in agitation rather than anxiolysis. Melatonin is an alternative preoperative anxiolytic; however, previous trials have delivered conflicting results. The aim of this non-inferiority trial was to evaluate the effectiveness of melatonin compared to midazolam in reducing anxiety in children undergoing general anaesthesia.</p><p><strong>Methods: </strong>We undertook a randomised-controlled, parallel-group, double-blind, non-inferiority trial in 20 United Kingdom National Health Service trusts, with an embedded qualitative study and health economic evaluation. Anxious children having day case elective surgery under general anaesthesia were randomly assigned to either control (standard of care) group: midazolam; or intervention group: melatonin. The primary outcome was preoperative distress (non-inferiority hypothesis) as assessed by modified Yale Preoperative Anxiety Scale Short Form. Secondary outcomes included safety and efficacy objectives. Analyses were by intention to treat, with an additional per-protocol analysis. The sample size of the trial was 624 children.</p><p><strong>Results: </strong>The trial was stopped early due to recruitment futility. Between 30 July 2019 and 9 November 2022, 110 children were recruited; 55 allocated to midazolam and 55 allocated to melatonin. Pre-planned analyses showed an adjusted mean difference of 13.1 (95% confidence interval 3.7 to 22.4) for the intention-to-treat population and 12.9 (95% confidence interval 3.1 to 22.6) for the per-protocol population, in favour of midazolam. In both analyses, the upper limit of the 95% confidence interval exceeds the predefined margin of 4.3; therefore, melatonin is not non-inferior to midazolam. The lower limit of the 95% confidence intervals excludes zero and thus melatonin is inferior to midazolam; the difference found is considered to be clinically meaningful. Adverse events in the midazolam arm (26%) were slightly higher than melatonin (18%); there were no serious adverse events in either arm. Challenges to recruitment included study-related factors (eligibility criteria and trial design), participant factors (caregiver stress on the day of treatment) and practitioner factors (valuing predictability). In terms of acceptability, preferences of the anaesthetist, patient and caregiver factors and medication side effects profile were influential and suggest the choice of preoperative anxiolytic is more complex than previously described. On average, costs over the 14 days post surgery were lower for","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":"29 29","pages":"1-25"},"PeriodicalIF":3.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12278375/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144575364","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":"Methylphenidate versus placebo for fatigue in patients with advanced cancer: the MePFAC randomised controlled trial.","authors":"Patrick Stone, Ollie Minton, Alison Richardson, Peter Buckle, Zinat E Enayat, Louise Marston, Nick Freemantle","doi":"10.3310/GJPS6321","DOIUrl":"10.3310/GJPS6321","url":null,"abstract":"<p><strong>Background: </strong>Previous meta-analyses suggested methylphenidate may be effective for cancer-related fatigue.</p><p><strong>Trial design: </strong>Phase III, parallel-group, randomised, double-blind, placebo-controlled trial.</p><p><strong>Methods: </strong>Participants were adults with advanced cancer with cancer-related fatigue receiving palliative care at 17 palliative care services in England between June 2018 and April 2023.</p><p><strong>Principal exclusions: </strong>Pregnancy; glaucoma; pheochromocytoma; planned general anaesthesia; hyperthyroidism; severe psychiatric disorders; hypertension; severe cardiovascular disorders; cerebrovascular disorders; anaemia; thrombocytopenia; leucopenia; infection; renal or liver impairment; concomitant clonidine, warfarin, monoamine oxidase inhibitors or modafinil; alcohol or drug dependency; epilepsy.</p><p><strong>Interventions: </strong>Methylphenidate 5 mg tablets or matching placebo. Starting at 1 tablet twice daily, titrated over 6 weeks to a maximum of 12 tablets/day.</p><p><strong>Objective: </strong>To estimate clinical effectiveness of methylphenidate versus placebo for cancer-related fatigue in patients receiving palliative care.</p><p><strong>Primary outcome: </strong>Fatigue at 6 (± 2) weeks measured using the Functional Assessment of Chronic Illness Therapy - Fatigue Scale score. Secondary outcomes were fatigue at other time points; quality of life, adverse events, activities of daily living; appetite; anxiety; depression; patient satisfaction; survival and need for other medication.</p><p><strong>Randomisation: </strong>Computer-generated 1 : 1 randomisation, stratified by centre, concomitant treatment, depression and initial fatigue score.</p><p><strong>Blinding: </strong>Participants and outcome assessors were blinded to group assignment.</p><p><strong>Results: </strong>Eighty-four were allocated to methylphenidate and 78 to placebo.</p><p><strong>Recruitment: </strong>: Study completed.</p><p><strong>Numbers analysed: </strong>Seventy-five in methylphenidate group and 72 in placebo group were included in analysis of primary outcome.</p><p><strong>Outcome: </strong>There was no statistically or clinically significant difference in primary outcome between groups. Functional Assessment of Chronic Illness Therapy - Fatigue Scale scores were 1.97 points (95% confidence interval -0.95 to 4.90; <i>p</i> = 0.186) higher (better) on methylphenidate than placebo. Functional Assessment of Chronic Illness Therapy - Fatigue Scale score was nominally statistically significantly higher (better) in methylphenidate group across duration of study [Diff 2.20 (95% confidence interval 0.39 to 4.01)] but did not reach the minimal clinically important difference (5 points). At 6 weeks, there were no statistically significant differences in quality-of-life or symptom domains except for depression scores [nominally statistically significantly reduced in methylphenidate group: Diff -1.35 (95% c","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":"29 36","pages":"1-47"},"PeriodicalIF":4.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12376206/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144775305","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":"Variation within and between digital pathology and light microscopy for the diagnosis of histopathology slides: blinded crossover comparison study.","authors":"David Rj Snead, Ayesha S Azam, Jenny Thirlwall, Peter Kimani, Louise Hiller, Adam Bickers, Clinton Boyd, David Boyle, David Clark, Ian Ellis, Kishore Gopalakrishnan, Mohammad Ilyas, Paul Kelly, Maurice Loughrey, Desley Neil, Emad Rakha, Ian Sd Roberts, Shatrughan Sah, Maria Soares, YeeWah Tsang, Manuel Salto-Tellez, Helen Higgins, Donna Howe, Abigail Takyi, Yan Chen, Agnieszka Ignatowicz, Jason Madan, Henry Nwankwo, George Partridge, Janet Dunn","doi":"10.3310/SPLK4325","DOIUrl":"10.3310/SPLK4325","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Digital pathology refers to the conversion of histopathology slides to digital image files for examination on computer workstations as opposed to conventional microscopes. Prior to adoption, it is important to demonstrate pathologists provide equivalent reports when using digital pathology in comparison to bright-field and immunofluorescent light microscopy, the current standard of care.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;A multicentre comparison of digital pathology with light microscopy for reporting of histopathology slides, measuring variation within and between pathologists on both modalities.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Design: &lt;/strong&gt;A blinded crossover 2000-case study estimating clinical management concordance (identical diagnoses plus differences not affecting patient management). Each sample was assessed twice by four pathologists (once using light microscopy, once using digital pathology, the order randomly assigned and a 6-week gap between viewings). Random-effects logistic regression models, including crossed random-effects terms for case and pathologist, estimated percentage clinical management concordance. Findings were interpreted with reference to 98.3% concordance (Azam AS, Miligy IM, Kimani PKU, Maqbool H, Hewitt K, Rajpoot NM, Snead DRJ. Diagnostic concordance and discordance in digital pathology: a systematic review and meta-analysis. &lt;i&gt;J Clin Pathol&lt;/i&gt; 2021;&lt;b&gt;74&lt;/b&gt;:448-55. https://doi.org/10.1136/jclinpath-2020-206764).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Setting: &lt;/strong&gt;Sixteen consultant pathologists, four for each specialty, from six National Health Service laboratories. Experience ranged from 3 to 35 years. Some were early adopters of digital pathology, but the majority were new to digital pathology.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Interventions: &lt;/strong&gt;Eight viewings per sample (four pathologists with light microscopy and with digital pathology), culminating in a consensus ground truth, enabling measurement of agreement within and between readers. Samples enrolled reflected routine practice, included cancer screening biopsies, and were enriched for areas of difficulty [e.g. dysplasia (7, 10, 11)]. State-of-the-art digital pathology equipment designed for diagnosis, and holding either Conformité Européene or Food and Drug Administration approval, was used.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main outcome: &lt;/strong&gt;Intra-pathologist variation between reports issued on digital pathology and light microscopy, inter-pathologist variation against ground-truth diagnosis using light microscopy and digital pathology.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Secondary outcomes: &lt;/strong&gt;Pathologist-recorded reporting times, along with their confidence in diagnosis, analysis of eye-tracking evaluating examination techniques, and a qualitative study examining attitudes of pathologists and laboratory staff to digital pathology adoption.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Two thousand and twenty-four cases (608 breast, 607 gastrointestinal, 609 skin, 200 renal) were recruited, with breast and gast","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":"29 30","pages":"1-75"},"PeriodicalIF":3.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12278374/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144626064","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":"Cessation of smoking in people attending UK emergency departments: the COSTED RCT with economic and process evaluation.","authors":"Ian Pope, Lucy V Clark, Allan Clark, Emma Ward, Pippa Belderson, Susan Stirling, Steve Parrott, Jinshuo Li, Timothy Coats, Linda Bauld, Richard Holland, Sarah Gentry, Sanjay Agrawal, Benjamin M Bloom, Adrian Boyle, Alasdair Gray, M Geraint Morris, Caitlin Notley","doi":"10.3310/JHFR0841","DOIUrl":"10.3310/JHFR0841","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;The emergency department represents a potentially valuable opportunity to support smoking cessation. Evidence is lacking around the use of e-cigarettes in opportunistic settings like the emergency department.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;To undertake a randomised controlled trial in people who smoke attending United Kingdom emergency departments, testing a brief intervention which included provision of an e-cigarette versus signposting to smoking cessation services, assessing smoking abstinence.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Design: &lt;/strong&gt;A two-arm pragmatic, multicentre, parallel-group, individually randomised, controlled superiority trial with an internal pilot, economic evaluation and mixed-methods process evaluation.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Setting: &lt;/strong&gt;Six emergency departments across England and Scotland.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants: &lt;/strong&gt;Adults who smoked daily, who were attending the emergency department for medical treatment or accompanying someone attending for medical treatment, were invited to participate. People were excluded if they had an expired carbon monoxide of &lt; 8 parts per million, required immediate medical treatment, were in police custody, had a known allergy to nicotine, were daily e-cigarette users, were considered not to have capacity to consent or had already taken part in the trial.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Intervention: &lt;/strong&gt;Brief stop smoking advice, e-cigarette starter kit and referral to stop smoking services.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main outcome measures: &lt;/strong&gt;The primary outcome was biochemically validated sustained abstinence at 6 months. Those lost to follow-up, or not providing biochemical verification, were considered not to be abstinent. Secondary outcomes were: self-reported 7-day smoking abstinence, number of quit attempts, number of cigarettes per day, nicotine dependence and incidence of self-reported dry cough or mouth or throat irritation.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;At 6 months, of 972 participants randomised, biochemically verified smoking abstinence was 7.2% in the intervention group and 4.1% in the control group (percentage difference = 3.3%) (95% confidence interval 0.3 to 6.3; &lt;i&gt;p&lt;/i&gt; = 0.032) [relative risk 1.76 (95% confidence interval 1.03 to 3.01)]. Self-reported 7-day abstinence at 6 months was 23.3% in the intervention group and 12.9% in the control group (percentage difference = 10.6%) (95% confidence interval 5.86 to 15.41; &lt;i&gt;p&lt;/i&gt; &lt; 0.001) [relative risk 1.80 (95% confidence interval 1.36 to 2.38)]. Daily e-cigarette use was 39.4% in the intervention group and 17.5% in the control group at 6 months. No serious adverse events related to taking part in the trial were reported. The economic evaluation found the intervention was likely to be cost-effective, judged by the National Institute for Health and Care Excellence threshold. The process evaluation found the intervention to be acceptable to both staff delivering it and participants receiving it. The brief nature of the i","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":"29 35","pages":"1-36"},"PeriodicalIF":4.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12376004/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144759961","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":"The risks, benefits, and resource implications of different diets in gastrostomy-fed children: The YourTube mixed method study.","authors":"Lorna Fraser, Andre Bedendo, Mark O'Neill, Johanna Taylor, Julia Hackett, Karen Horridge, Janet Cade, Gerry Richardson, Thai Han Phung, Bryony Beresford, Alison McCarter, Catherine Hewitt","doi":"10.3310/RRREF7741","DOIUrl":"10.3310/RRREF7741","url":null,"abstract":"<p><strong>Background: </strong>Many children receive some or all their nutritional intake via a gastrostomy. More parents are using home-blended meals to feed their children, reporting beneficial effects, such as improved gastro-oesophageal reflux and less distress.</p><p><strong>Aim: </strong>To compare safety, outcomes and resource use of those on home-blended diets compared to formula diets.</p><p><strong>Methods: </strong>A mixed-methods study of gastrostomy-fed children.</p><p><strong>Workstream 1: </strong>Qualitative study involving semistructured interviews with parents (<i>n </i>≈ 20) and young people (<i>n </i>≈ 2) and focus groups with health professionals (<i>n </i>≈ 41).</p><p><strong>Workstream 2: </strong>Cohort study; data were collected on 180 children at months 0, 12 and 18 from parents and clinicians using standardised measures. Data included gastrointestinal symptoms, quality of life, sleep (child and parent), dietary intake, anthropometry, healthcare usage, safety outcomes and resource use. Outcomes were compared using propensity scored weighted multiple regression analyses.</p><p><strong>Results: workstream 1: </strong>Participants believed the type of diet would most likely affect gastrointestinal symptoms, time spent on feeding, sleep and physical health.</p><p><strong>Workstream 2: </strong><b>Baseline</b>: Children receiving a home-blended diet and those receiving a formula diet were similar in terms of diagnoses and age, but those receiving a home-blended diet were more likely to live in areas of lower deprivation and their parents had higher levels of education. They also had a higher dietary fibre intake and demonstrated significantly better gastrointestinal symptom scores compared to those receiving a formula diet (beta 13.8, <i>p</i> < 0.001). The number of gut infections and tube blockages were similar between the two groups, but stoma site infections were lower in those receiving a home-blended diet. <b>Follow-up</b>: There were 134 (74%) and 105 (58%) children who provided follow-up data at 12 and 18 months. Gastrointestinal symptoms were lower at all time points in the home-blended diet group, but there was no difference in change over time within or between the groups. The nutritional intake of those on a home-blended diet had higher calories/kg and fibre, and both home-blended and formula-fed children have values above the Dietary Reference Values for most micronutrients. Safety outcomes were similar between groups and over time. Total costs to the statutory sector were higher among children who were formula fed, but costs of purchasing special equipment for home-blended food and the total time spent on child care were higher for families with home-blended diet.</p><p><strong>Conclusion: </strong>Findings show that home-blended diets for children who are gastrostomy fed should be seen as a safe alternative to formula feeding for children unless there is a clinical contraindication.</p><p><strong>Limitations: ","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":"29 25","pages":"1-21"},"PeriodicalIF":3.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12278030/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144575361","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":"BioImpedance Spectroscopy to maintain Renal Output: the BISTRO randomised controlled trial.","authors":"Simon J Davies, David Coyle, Elizabeth Lindley, David Keane, John Belcher, Fergus Caskey, Indranil Dasgupta, Andrew Davenport, Ken Farrington, Sandip Mitra, Paula Ormandy, Martin Wilkie, Jamie MacDonald, Mandana Zanganeh, Lazaros Andronis, Ivonne Solis-Trapala, Julius Sim","doi":"10.3310/RHON2378","DOIUrl":"10.3310/RHON2378","url":null,"abstract":"<p><strong>Background: </strong>Fluid removal is a key component of dialysis treatment but, if excessive, can result in a faster decline in residual kidney function. Prescribing the optimal removal of fluid on dialysis to avoid this is therefore important. Bioimpedance spectroscopy, a bedside device that estimates tissue hydration, might improve this prescription, so reducing the rate of decline in kidney function and improving patient outcomes. We wished to establish the efficacy and cost-effectiveness of bioimpedance in pursuing this treatment strategy.</p><p><strong>Methods: </strong>We undertook a multicentre, open-label, parallel, individually randomised controlled trial in incident haemodialysis patients, with clinicians and patients blinded to bioimpedance readings in the control group. Eligible patients had a urine output of > 500 ml/day or a glomerular filtration rate > 3 ml/minute/1.73 m². Randomisation was 1 : 1 using a concealed automated computer-generated allocation system stratified by centre. Clinical assessments were made monthly for 3 months and then every 3 months for up to 24 months using a standardised proforma in both groups, supplemented in the intervention group by the bioimpedance estimate of the normally hydrated weight. The primary outcome was time to anuria; secondary outcomes were rate in decline of residual kidney function, blood pressure, dialysis-related symptoms (Integrated Palliative Care Outcome Scale-Renal), quality of life (EuroQol) and incremental cost per additional quality-adjusted life-year gained.</p><p><strong>Results: </strong>Four hundred and thirty-nine patients were recruited and analysed from 34 United Kingdom centres. There were no between-group differences in cause-specific hazard rates of anuria, 0.751 (95% confidence interval 0.459 to 1.229) or subdistribution hazard rates 0.742 (95% confidence interval 0.453 to 1.215). Kidney function decline was slower than anticipated, pooled linear rates in year 1: -0.178 (95% confidence interval -0.196 to -0.159) ml/minute/1.73 m²/month; year 2: -0.061 (95% confidence interval -0.086 to -0.036) ml/minute/1.73 m²/month. Longitudinal blood pressure, symptoms and patient-reported outcomes did not differ by group. The intervention was associated with £382 (95% confidence interval -£3319 to £2556) lower average cost per patient (price year 2020) and 0.043 (95% confidence interval -0.019 to -0.105) more quality-adjusted life-years and no harm compared to control. A post hoc 5-year analysis found better survival with more residual kidney function at enrolment and at any time over the next 2 years.</p><p><strong>Conclusion: </strong>The use of a standardised clinical protocol for fluid assessment to avoid excessive fluid removal is associated with excellent preservation of residual kidney function and better medium-term survival in this cohort. Bioimpedance measurements are not necessary to achieve this. Probability of the intervent","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":"29 32","pages":"1-23"},"PeriodicalIF":4.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12336963/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144775302","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":"Extracorporeal carbon dioxide removal for the treatment of acute hypoxaemic respiratory failure: the REST RCT.","authors":"James J McNamee, Ashley Agus, Andrew J Boyle, Colette Jackson, Cliona McDowell, Jeanette Haglund, Danny F McAuley","doi":"10.3310/GJDM0320","DOIUrl":"10.3310/GJDM0320","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;In patients who require mechanical ventilation for acute hypoxaemic respiratory failure, further reduction in tidal volumes, compared with conventional low tidal volume ventilation, may improve outcomes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;To determine whether using extracorporeal carbon dioxide removal improves outcomes in patients with acute hypoxaemic respiratory failure and is cost-effective.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Design: &lt;/strong&gt;A multicentre, randomised, allocation-concealed, open-label, pragmatic clinical trial.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Setting: &lt;/strong&gt;Fifty-one intensive care units across the United Kingdom.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants: &lt;/strong&gt;Four hundred and twelve adult patients receiving mechanical ventilation for acute hypoxaemic respiratory failure, of a planned sample size of 1120.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Interventions: &lt;/strong&gt;Lower tidal volume ventilation facilitated by extracorporeal carbon dioxide removal for at least 48 hours (&lt;i&gt;n&lt;/i&gt; = 202) or standard care with conventional low tidal volume ventilation (&lt;i&gt;n&lt;/i&gt; = 210).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main outcome measures: &lt;/strong&gt;All-cause mortality 90 days. Secondary outcomes included ventilator-free days; adverse events; extracorporeal membrane oxygenation use; long-term mortality; health-related quality of life; health service costs; long-term respiratory morbidity.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The trial was stopped early because of futility and feasibility. The 90-day mortality rate was 41.5% in the extracorporeal carbon dioxide removal group versus 39.5% in the standard care group (risk ratio 1.05, 95% confidence interval 0.83 to 1.33; difference 2.0%, 95% confidence interval  - 7.6% to 11.5%; &lt;i&gt;p&lt;/i&gt; = 0.68). There were significantly fewer mean ventilator-free days in the extracorporeal carbon dioxide removal group compared with the standard care group (7.1, 95% confidence interval 5.9 to 8.3) versus (9.2, 95% confidence interval 7.9 to 10.4) days; mean difference, -2.1 (95% confidence interval -3.8 to -0.3; &lt;i&gt;p&lt;/i&gt; = 0.02). Serious adverse events were reported for 62 patients (31%) in extracorporeal carbon dioxide removal group and 18 (9%) in the standard care group, including intracranial haemorrhage in 9 patients (4.5%) versus 0 (0%) and bleeding at other sites in 6 (3.0%) versus 1 (0.5%) in the extracorporeal carbon dioxide removal group versus the control group. Two-year mortality data were available for 95% of patients. There was no difference in the time to death between groups (hazard ratio 1.08, 95% confidence interval 0.81 to 1.44; log-rank test &lt;i&gt;p&lt;/i&gt; = 0.61). There was no difference in long-term outcomes between groups. There was no difference in quality-adjusted life-years at 12 months (mean difference -0.01, 95% confidence interval -0.06 to 0.05). Total 12-month costs were statistically significantly higher in the extracorporeal carbon dioxide removal group (mean difference £7668.76, 95% confidence interval £159.75 to £15,177.77). Secondary analyses indic","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":"29 33","pages":"1-16"},"PeriodicalIF":4.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12376005/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144775303","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":"Urodynamics tests for the diagnosis and management of male bladder outlet obstruction: long-term follow-up of the UPSTREAM non-inferiority RCT.","authors":"Madeleine Clout, Amanda L Lewis, Madeleine Cochrane, Grace J Young, Paul Abrams, Peter S Blair, Christopher Chapple, Gordon T Taylor, Sian Noble, Tom Steuart-Feilding, Jodi Taylor, J Athene Lane, Marcus J Drake","doi":"10.3310/SLPT4675","DOIUrl":"10.3310/SLPT4675","url":null,"abstract":"<p><strong>Background: </strong>Lower urinary tract symptoms are common in older men and can be bothersome, leading to treatment. The UPSTREAM randomised controlled trial (Phase I) investigated whether assessment of these symptoms with invasive urodynamic testing could improve symptoms when guiding treatment options.</p><p><strong>Objective: </strong>To assess the long-term lower urinary tract symptoms and the rates of surgery for bladder outlet obstruction in men participating in the UPSTREAM study (Phase I).</p><p><strong>Design: </strong>Pragmatic, multicentre, parallel-group, two-group open randomised controlled study, with outcome assessors blinded to aggregate data.</p><p><strong>Setting: </strong>Urology departments of 26 National Health Service hospitals in England.</p><p><strong>Participants: </strong>Men ≥ 18 years, seeking further treatment for their bothersome lower urinary tract symptoms, which may include surgery, who were existing participants of the UPSTREAM study (Phase I). Men were excluded if they were unable to pass urine without a catheter, had a relevant neurological disease, were currently undergoing treatment for prostate or bladder cancer, had previous prostate surgery or were unfit for surgery.</p><p><strong>Interventions: </strong>Routine care plus invasive urodynamics (intervention) or non-invasive routine care.</p><p><strong>Main outcome measures: </strong>The primary outcome was a patient-reported International Prostate Symptom Score 5 years post randomisation. Rates of surgery was the key secondary outcome. Patient-reported outcomes included measures of lower urinary tract symptoms, sexual function, overall quality of life and cost-effectiveness from a secondary care perspective.</p><p><strong>Data sources: </strong>Questionnaires to participants for patient-reported outcome measures, and National Health Service England Hospital Episode Statistics and mortality data.</p><p><strong>Results: </strong>Of 820 men randomised in UPSTREAM (Phase I) between October 2014 and December 2016, 211/427 men randomised to the intervention group completed Phase II questionnaires (49.4%) and 205/363 in the routine care group (56.5%). There was no difference found between International Prostate Symptom Scores in the two groups at 5 years (adjusted difference 0.41, 95% confidence interval -1.10 to 1.93). There was also no difference in other lower urinary tract symptoms, sexual function or quality of life. Routine data were received for 98% of men. Three hundred and forty-seven (43.3%) men with routine data available had received at least one related surgical procedure for the treatment of lower urinary tract symptoms. Over the 5-year time horizon, incremental mean costs were slightly higher (£176.63, 95% confidence interval -£464.06 to £817.32) in the intervention group and incremental mean QALYs were slightly lower (-0.039, 95% confidence interval -0.152 to 0.073) in the intervention group. This suggests that routine care is the cost","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":"29 26","pages":"1-57"},"PeriodicalIF":3.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12278039/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144575362","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":"The quantity, quality and findings of network meta-analyses evaluating the effectiveness of GLP-1 RAs for weight loss: a scoping review.","authors":"Michael Nunns, Samantha Febrey, Jill Buckland, Rebecca Abbott, Rebecca Whear, Alison Bethel, Kate Boddy, Liz Shaw, Jo Thompson Coon, G J Melendez-Torres","doi":"10.3310/SKHT8119","DOIUrl":"10.3310/SKHT8119","url":null,"abstract":"<p><strong>Background: </strong>Glucagon-like peptide 1 receptor agonists are a class of drug originally developed to treat type 2 diabetes but now increasingly used for weight loss, especially in people living with obesity. Despite an abundance of evidence about the effectiveness and safety of glucagon-like peptide 1 receptor agonists for weight loss, network meta-analyses are inconsistent in their quality and scope, and this is a fast-moving field.</p><p><strong>Objectives: </strong>We sought to identify the most recent network meta-analyses evaluating the effectiveness of glucagon-like peptide 1 receptor agonists for weight loss; critically appraise included network meta-analyses; provide an overview of the quality and findings of existing network meta-analyses, and identify any pertinent gaps in the evidence; and consider the value of updating the most recent, comprehensive and high-quality network meta-analyses.</p><p><strong>Methods: </strong>On 6 June 2023, we searched MEDLINE, EMBASE, the Cochrane Database of Systematic Reviews and Epistemonikos for systematic reviews with network meta-analyses published since 2020 in adults (18 or above) with body mass index ≥ 25 (or ≥ 23 for Asian populations), including at least one relevant glucagon-like peptide 1 receptor agonist and weight loss outcomes. We screened and selected reviews in duplicate and independently, and appraised reviews using a modified A MeaSurement Tool to Assess systematic Reviews 2 (AMSTAR-2) and a network meta-analysis reliability checklist. The highest-quality reviews were then extracted in depth, and the most relevant network meta-analysis models identified, focusing on weight loss and safety outcomes. A top-up search for trials published since October 2022 was also undertaken to identify relevant trials not included in published network meta-analyses. A further search for new network meta-analyses was conducted on 26 September 2024.</p><p><strong>Results: </strong>Of 22 systematic reviews identified, 14 were prioritised for analysis as the remaining 8 reviews were rated as low or critically low quality. We focused on network meta-analyses of weight loss outcomes measured at 6 months, 12 months, longer than 12 months or over a mix of time points. At 6 months, subcutaneous tirzepatide was the most effective drug associated with 9 kg (at 5 mg) to 12 kg (at 15 mg) of weight loss. However, the largest effects were seen for subcutaneous semaglutide 2.4 mg, which was associated with between 11.5 and 12.5 kg of weight loss, though this came from two network meta-analyses, both informed by six trials, and both merging findings across multiple time points. The relative effectiveness among glucagon-like peptide 1 receptor agonists followed a pattern suggested by their performance against placebo, with tirzepatide and semaglutide standing out as the most effective drugs for weight loss. No network meta-analyses compared tirzepatide and semaglutide 2.4 mg. The drugs associated with th","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":" ","pages":"1-73"},"PeriodicalIF":4.0,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12336958/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144527680","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":"Establishing the best step-up treatments for children with uncontrolled asthma despite inhaled corticosteroids: the EINSTEIN systematic review, network meta-analysis and cost-effectiveness analysis using individual participant data.","authors":"Sofia Cividini, Ian Sinha, Giovanna Culeddu, Sarah Donegan, Michelle Maden, Katie Rose, Olivia Fulton, Dyfrig Hughes, Stephen Turner, Catrin Tudur Smith","doi":"10.3310/HGWT3617","DOIUrl":"10.3310/HGWT3617","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;There is no clear preferential option for initial step-up of treatment for children with uncontrolled asthma on inhaled corticosteroid.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objectives: &lt;/strong&gt;Evaluate the clinical effectiveness of pharmacological treatments to use in children with uncontrolled asthma on inhaled corticosteroid; identify and evaluate the potential for treatment effect modification to optimise treatment delivery; assess the cost-effectiveness of treatments.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Systematic review and individual participant data network meta-analysis. Studies were eligible if they were parallel or crossover randomised controlled trials comparing at least one of the pharmacological treatments of interest in participants aged &lt; 18 years with uncontrolled asthma on any dose inhaled corticosteroid alone. We searched MEDLINE&lt;sup&gt;®&lt;/sup&gt;, Cochrane Library, Cochrane Central Register of Controlled Trials, EMBASE, National Institute for Health and Care Excellence Technology Appraisals, and the National Institute for Health and Care Research Health Technology Assessment series. Primary outcomes: exacerbation and asthma control. Secondary outcomes: health-related quality of life, mortality, forced expiratory volume in 1 second, adverse events, hospital admissions, symptoms (not analysed). We assessed the Risk Of Bias using the Cochrane Risk Of Bias tool and carried out Bayesian meta-analyses, network meta-analysis and network meta-regression, including treatment by covariate (age, sex, ethnicity, eczema, eosinophilia, asthma severity) interactions. A Markov decision-analytic model with a 12-month time horizon, which adopted the perspective of the National Health Service and Personal Social Services in the United Kingdom, was developed to compare alternative treatments. Cost-effectiveness was based on incremental costs per quality-adjusted life-years gained, with uncertainty considered in one-way, structural and probabilistic sensitivity analyses.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;We identified and screened 4708 publications from the search and confirmed 144 randomised controlled trials as eligible. We obtained individual participant data from 29 trials (5381 participants) and extracted limited aggregate data from a further 19 trials. The majority of trials had low risk of bias. The network meta-analysis suggests that medium-dose inhaled corticosteroid + long-acting &lt;i&gt;β&lt;/i&gt;&lt;sub&gt;2&lt;/sub&gt;-agonist is the preferred treatment for reducing odds of exacerbation [odds ratio 95% credibility interval: 0.43 (0.20 to 0.92) vs. low-dose inhaled corticosteroid; 40 studies, 8168 patients] and increasing forced expiratory volume in 1 second [mean difference 95% credibility interval: 0.71 (0.35 to 1.06) vs. low-dose inhaled corticosteroid; 23 studies, 2518 patients] while leukotriene receptor antagonist alone is the least preferred. No clear differences were found for asthma control (16 studies, 3027 patients). Limited pairwise analyses sugges","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":"29 15","pages":"1-234"},"PeriodicalIF":3.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12104851/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144093426","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}