Olalekan A Uthman, Rachel Court, Jodie Enderby, Chidozie Nduka, Lena Al-Khudairy, Seun Anjorin, Hema Mistry, G J Melendez-Torres, Sian Taylor-Phillips, Aileen Clarke
Background: Cardiovascular disease accounts for substantial mortality and healthcare costs worldwide. Numerous interventions exist for primary prevention but lack head-to-head comparisons on long-term impacts.
Objective: To determine the comparative effectiveness of interventions for primary cardiovascular disease prevention through network meta-analysis of randomised trials.
Data sources: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, conference abstracts and trial registries from inception to March 2021.
Review methods: Randomised controlled trials of pharmacologic therapies, nutritional supplements, lifestyle changes, behavioural approaches and health policies with at least 6 months' follow-up were included. Pairwise and network meta-analyses were conducted for all-cause mortality, cardiovascular disease events, coronary heart disease and cardiovascular disease mortality.
Results: Data from 139 randomised trials, including 1,053,772 participants, proved suitable for quantitative synthesis. Blood pressure-lowering medications (risk ratio 0.82, 95% confidence interval 0.71 to 0.94), tight blood pressure control (risk ratio 0.66, 95% confidence interval 0.46 to 0.96), statins (risk ratio 0.81, 95% confidence interval 0.71 to 0.91) and multifactorial lifestyle interventions (risk ratio 0.75, 95% confidence interval 0.61 to 0.92) reduced composite cardiovascular events and mortality.
Limitations: Residual confounding may exist. Few direct head-to-head comparisons limited differentiation between some specific modalities.
Conclusions: We found evidence that blood pressure treatments, intense blood pressure targets, statins when appropriate and multifactorial lifestyle changes are the most effective strategies for primary prevention of cardiovascular disease, with unclear effects from other interventions. These findings can inform clinical guidelines and health policies prioritising interventions.
Funding: This research article presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number 17/148/05.
背景：心血管疾病在世界范围内造成了大量的死亡率和医疗费用。存在许多初级预防干预措施，但缺乏对长期影响的正面比较。目的：通过随机试验的网络荟萃分析，确定初级心血管疾病预防干预措施的比较有效性。数据来源：MEDLINE， EMBASE, Cochrane Central Register of Controlled Trials，会议摘要和从成立到2021年3月的试验注册。回顾方法：纳入药物治疗、营养补充剂、生活方式改变、行为方法和健康政策的随机对照试验，随访至少6个月。对全因死亡率、心血管疾病事件、冠心病和心血管疾病死亡率进行两两和网络荟萃分析。结果：139项随机试验的数据，包括1,053,772名参与者，证明适合定量合成。降压药（风险比0.82,95%置信区间0.71 ~ 0.94）、严格血压控制（风险比0.66,95%置信区间0.46 ~ 0.96）、他汀类药物（风险比0.81,95%置信区间0.71 ~ 0.91）和多因素生活方式干预（风险比0.75,95%置信区间0.61 ~ 0.92）降低了复合心血管事件和死亡率。局限性：可能存在残留混淆。很少有直接的正面比较限制了某些特定模式之间的区别。结论：我们发现有证据表明，血压治疗、高强度血压目标、适当时使用他汀类药物和多因素生活方式改变是心血管疾病一级预防最有效的策略，其他干预措施的效果尚不清楚。这些发现可以为临床指南和优先考虑干预措施的卫生政策提供信息。资助：这篇研究文章介绍了由国家卫生与保健研究所（NIHR）卫生技术评估项目资助的独立研究，奖励号为17/148/05。
{"title":"Identifying optimal primary prevention interventions for major cardiovascular disease events and all-cause mortality: a systematic review and hierarchical network meta-analysis of RCTs.","authors":"Olalekan A Uthman, Rachel Court, Jodie Enderby, Chidozie Nduka, Lena Al-Khudairy, Seun Anjorin, Hema Mistry, G J Melendez-Torres, Sian Taylor-Phillips, Aileen Clarke","doi":"10.3310/RLDH7432","DOIUrl":"10.3310/RLDH7432","url":null,"abstract":"<p><strong>Background: </strong>Cardiovascular disease accounts for substantial mortality and healthcare costs worldwide. Numerous interventions exist for primary prevention but lack head-to-head comparisons on long-term impacts.</p><p><strong>Objective: </strong>To determine the comparative effectiveness of interventions for primary cardiovascular disease prevention through network meta-analysis of randomised trials.</p><p><strong>Data sources: </strong>MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, conference abstracts and trial registries from inception to March 2021.</p><p><strong>Review methods: </strong>Randomised controlled trials of pharmacologic therapies, nutritional supplements, lifestyle changes, behavioural approaches and health policies with at least 6 months' follow-up were included. Pairwise and network meta-analyses were conducted for all-cause mortality, cardiovascular disease events, coronary heart disease and cardiovascular disease mortality.</p><p><strong>Results: </strong>Data from 139 randomised trials, including 1,053,772 participants, proved suitable for quantitative synthesis. Blood pressure-lowering medications (risk ratio 0.82, 95% confidence interval 0.71 to 0.94), tight blood pressure control (risk ratio 0.66, 95% confidence interval 0.46 to 0.96), statins (risk ratio 0.81, 95% confidence interval 0.71 to 0.91) and multifactorial lifestyle interventions (risk ratio 0.75, 95% confidence interval 0.61 to 0.92) reduced composite cardiovascular events and mortality.</p><p><strong>Limitations: </strong>Residual confounding may exist. Few direct head-to-head comparisons limited differentiation between some specific modalities.</p><p><strong>Conclusions: </strong>We found evidence that blood pressure treatments, intense blood pressure targets, statins when appropriate and multifactorial lifestyle changes are the most effective strategies for primary prevention of cardiovascular disease, with unclear effects from other interventions. These findings can inform clinical guidelines and health policies prioritising interventions.</p><p><strong>Funding: </strong>This research article presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number 17/148/05.</p>","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":" ","pages":"1-65"},"PeriodicalIF":4.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12376007/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560003","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}
Mohamed Abdel-Fattah, Christopher Chapple, Suzanne Breeman, David Cooper, Helen Bell-Gorrod, Preksha Kuppanda, Karen Guerrero, Simon Dixon, Nikki Cotterill, Karen Ward, Hashim Hashim, Ash Monga, Karen Brown, Marcus Drake, Andrew Gammie, Alyaa Mostafa, Rebecca Bruce, Victoria Bell, Christine Kennedy, Suzanne Evans, Graeme MacLennan, John Norrie
<p><strong>Background: </strong>Overactive bladder is a common problem affecting the United Kingdom adult female population. Symptoms include urinary urgency, with or without urgency incontinence, increased daytime urinary frequency and nocturia. Initial conservative treatments for overactive bladder are unsuccessful in 25-40% of women (refractory overactive bladder). Before considering invasive treatments, such as botulinum toxin injection-A or sacral neuromodulation, guidelines recommend urodynamics to confirm diagnosis of detrusor overactivity. However, the clinical and cost effectiveness of urodynamics has never been robustly assessed.</p><p><strong>Objectives: </strong>To compare the clinical and cost effectiveness of urodynamics plus comprehensive clinical assessment versus comprehensive clinical assessment only in the management of refractory overactive bladder in women.</p><p><strong>Design: </strong>Parallel-group, multicentre, superiority, open-label, randomised controlled trial. Allocation by remote web-based randomisation (1 : 1 ratio). The cost-effectiveness analysis took the National Health Service perspective with a model-based lifetime time horizon, as informed by a within-trial analysis.</p><p><strong>Setting: </strong>Sixty-three United Kingdom secondary and tertiary hospitals.</p><p><strong>Participants: </strong>Women aged ≥ 18 years with refractory overactive bladder or urgency-predominant mixed urinary incontinence who had failed conservative management and pharmacological treatment and were being considered for invasive treatment. Women were excluded if any of the following criteria were met: predominant stress urinary incontinence; previous urodynamics in last 12 months; current pelvic malignancy or clinically significant pelvic mass; bladder pain syndrome; neurogenic bladder; urogenital fistulae; previous treatment with botulinum toxin injection-A or sacral neuromodulation for urinary incontinence; previous pelvic radiotherapy; prolapse beyond introitus; pregnant or planning pregnancy; recurrent urinary tract infection where a significant pathology has not been excluded; and inability to give an informed consent.</p><p><strong>Interventions: </strong>Urodynamics plus comprehensive clinical assessment (urodynamics arm) versus comprehensive clinical assessment only.</p><p><strong>Main outcome measures: </strong>Participant-reported success at the last follow-up time point as measured by the Patient Global Impression of Improvement. Primary economic outcome was incremental cost per quality-adjusted life-year gained as modelled over the lifetime of participants.</p><p><strong>Results: </strong>A total of 1099 participants were included: 550 randomised to the urodynamics arm and 549 to the comprehensive clinical assessment only arm. At the final follow-up time point, participant-reported success rates of 'very much improved' and 'much improved' were not superior in the urodynamics arm (117 participants; 23.6%) compared to the
{"title":"Invasive urodynamic investigations in the management of women with refractory overactive bladder symptoms: FUTURE, a superiority RCT and economic evaluation.","authors":"Mohamed Abdel-Fattah, Christopher Chapple, Suzanne Breeman, David Cooper, Helen Bell-Gorrod, Preksha Kuppanda, Karen Guerrero, Simon Dixon, Nikki Cotterill, Karen Ward, Hashim Hashim, Ash Monga, Karen Brown, Marcus Drake, Andrew Gammie, Alyaa Mostafa, Rebecca Bruce, Victoria Bell, Christine Kennedy, Suzanne Evans, Graeme MacLennan, John Norrie","doi":"10.3310/UKYW4923","DOIUrl":"10.3310/UKYW4923","url":null,"abstract":"<p><strong>Background: </strong>Overactive bladder is a common problem affecting the United Kingdom adult female population. Symptoms include urinary urgency, with or without urgency incontinence, increased daytime urinary frequency and nocturia. Initial conservative treatments for overactive bladder are unsuccessful in 25-40% of women (refractory overactive bladder). Before considering invasive treatments, such as botulinum toxin injection-A or sacral neuromodulation, guidelines recommend urodynamics to confirm diagnosis of detrusor overactivity. However, the clinical and cost effectiveness of urodynamics has never been robustly assessed.</p><p><strong>Objectives: </strong>To compare the clinical and cost effectiveness of urodynamics plus comprehensive clinical assessment versus comprehensive clinical assessment only in the management of refractory overactive bladder in women.</p><p><strong>Design: </strong>Parallel-group, multicentre, superiority, open-label, randomised controlled trial. Allocation by remote web-based randomisation (1 : 1 ratio). The cost-effectiveness analysis took the National Health Service perspective with a model-based lifetime time horizon, as informed by a within-trial analysis.</p><p><strong>Setting: </strong>Sixty-three United Kingdom secondary and tertiary hospitals.</p><p><strong>Participants: </strong>Women aged ≥ 18 years with refractory overactive bladder or urgency-predominant mixed urinary incontinence who had failed conservative management and pharmacological treatment and were being considered for invasive treatment. Women were excluded if any of the following criteria were met: predominant stress urinary incontinence; previous urodynamics in last 12 months; current pelvic malignancy or clinically significant pelvic mass; bladder pain syndrome; neurogenic bladder; urogenital fistulae; previous treatment with botulinum toxin injection-A or sacral neuromodulation for urinary incontinence; previous pelvic radiotherapy; prolapse beyond introitus; pregnant or planning pregnancy; recurrent urinary tract infection where a significant pathology has not been excluded; and inability to give an informed consent.</p><p><strong>Interventions: </strong>Urodynamics plus comprehensive clinical assessment (urodynamics arm) versus comprehensive clinical assessment only.</p><p><strong>Main outcome measures: </strong>Participant-reported success at the last follow-up time point as measured by the Patient Global Impression of Improvement. Primary economic outcome was incremental cost per quality-adjusted life-year gained as modelled over the lifetime of participants.</p><p><strong>Results: </strong>A total of 1099 participants were included: 550 randomised to the urodynamics arm and 549 to the comprehensive clinical assessment only arm. At the final follow-up time point, participant-reported success rates of 'very much improved' and 'much improved' were not superior in the urodynamics arm (117 participants; 23.6%) compared to the ","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":"29 27","pages":"1-139"},"PeriodicalIF":3.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12278378/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144575363","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}
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
<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
{"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}
Patrick Stone, Ollie Minton, Alison Richardson, Peter Buckle, Zinat E Enayat, Louise Marston, Nick Freemantle
Background: Previous meta-analyses suggested methylphenidate may be effective for cancer-related fatigue.
Trial design: Phase III, parallel-group, randomised, double-blind, placebo-controlled trial.
Methods: 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.
Principal exclusions: 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.
Interventions: Methylphenidate 5 mg tablets or matching placebo. Starting at 1 tablet twice daily, titrated over 6 weeks to a maximum of 12 tablets/day.
Objective: To estimate clinical effectiveness of methylphenidate versus placebo for cancer-related fatigue in patients receiving palliative care.
Primary outcome: 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.
Randomisation: Computer-generated 1 : 1 randomisation, stratified by centre, concomitant treatment, depression and initial fatigue score.
Blinding: Participants and outcome assessors were blinded to group assignment.
Results: Eighty-four were allocated to methylphenidate and 78 to placebo.
Recruitment: : Study completed.
Numbers analysed: Seventy-five in methylphenidate group and 72 in placebo group were included in analysis of primary outcome.
Outcome: 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; p = 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
{"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}
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
<p><strong>Background: </strong>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.</p><p><strong>Objective: </strong>A multicentre comparison of digital pathology with light microscopy for reporting of histopathology slides, measuring variation within and between pathologists on both modalities.</p><p><strong>Design: </strong>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. <i>J Clin Pathol</i> 2021;<b>74</b>:448-55. https://doi.org/10.1136/jclinpath-2020-206764).</p><p><strong>Setting: </strong>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.</p><p><strong>Interventions: </strong>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.</p><p><strong>Main outcome: </strong>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.</p><p><strong>Secondary outcomes: </strong>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.</p><p><strong>Results: </strong>Two thousand and twenty-four cases (608 breast, 607 gastrointestinal, 609 skin, 200 renal) were recruited, with breast and gast
{"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":"<p><strong>Background: </strong>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.</p><p><strong>Objective: </strong>A multicentre comparison of digital pathology with light microscopy for reporting of histopathology slides, measuring variation within and between pathologists on both modalities.</p><p><strong>Design: </strong>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. <i>J Clin Pathol</i> 2021;<b>74</b>:448-55. https://doi.org/10.1136/jclinpath-2020-206764).</p><p><strong>Setting: </strong>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.</p><p><strong>Interventions: </strong>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.</p><p><strong>Main outcome: </strong>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.</p><p><strong>Secondary outcomes: </strong>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.</p><p><strong>Results: </strong>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}
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
<p><strong>Background: </strong>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.</p><p><strong>Objective: </strong>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.</p><p><strong>Design: </strong>A two-arm pragmatic, multicentre, parallel-group, individually randomised, controlled superiority trial with an internal pilot, economic evaluation and mixed-methods process evaluation.</p><p><strong>Setting: </strong>Six emergency departments across England and Scotland.</p><p><strong>Participants: </strong>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 < 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.</p><p><strong>Intervention: </strong>Brief stop smoking advice, e-cigarette starter kit and referral to stop smoking services.</p><p><strong>Main outcome measures: </strong>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.</p><p><strong>Results: </strong>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; <i>p</i> = 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; <i>p</i> < 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
{"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":"<p><strong>Background: </strong>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.</p><p><strong>Objective: </strong>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.</p><p><strong>Design: </strong>A two-arm pragmatic, multicentre, parallel-group, individually randomised, controlled superiority trial with an internal pilot, economic evaluation and mixed-methods process evaluation.</p><p><strong>Setting: </strong>Six emergency departments across England and Scotland.</p><p><strong>Participants: </strong>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 < 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.</p><p><strong>Intervention: </strong>Brief stop smoking advice, e-cigarette starter kit and referral to stop smoking services.</p><p><strong>Main outcome measures: </strong>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.</p><p><strong>Results: </strong>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; <i>p</i> = 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; <i>p</i> < 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}
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
Background: 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.
Aim: To compare safety, outcomes and resource use of those on home-blended diets compared to formula diets.
Methods: A mixed-methods study of gastrostomy-fed children.
Workstream 1: Qualitative study involving semistructured interviews with parents (n ≈ 20) and young people (n ≈ 2) and focus groups with health professionals (n ≈ 41).
Workstream 2: 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.
Results: workstream 1: Participants believed the type of diet would most likely affect gastrointestinal symptoms, time spent on feeding, sleep and physical health.
Workstream 2: Baseline: 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, p < 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. Follow-up: 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.
Conclusion: 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.
{"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}
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
Background: 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.
Methods: 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.
Results: 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.
Conclusion: 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
{"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 m<sup>2</sup>. 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 m<sup>2</sup>/month; year 2: -0.061 (95% confidence interval -0.086 to -0.036) ml/minute/1.73 m<sup>2</sup>/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}
James J McNamee, Ashley Agus, Andrew J Boyle, Colette Jackson, Cliona McDowell, Jeanette Haglund, Danny F McAuley
<p><strong>Background: </strong>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.</p><p><strong>Objective: </strong>To determine whether using extracorporeal carbon dioxide removal improves outcomes in patients with acute hypoxaemic respiratory failure and is cost-effective.</p><p><strong>Design: </strong>A multicentre, randomised, allocation-concealed, open-label, pragmatic clinical trial.</p><p><strong>Setting: </strong>Fifty-one intensive care units across the United Kingdom.</p><p><strong>Participants: </strong>Four hundred and twelve adult patients receiving mechanical ventilation for acute hypoxaemic respiratory failure, of a planned sample size of 1120.</p><p><strong>Interventions: </strong>Lower tidal volume ventilation facilitated by extracorporeal carbon dioxide removal for at least 48 hours (<i>n</i> = 202) or standard care with conventional low tidal volume ventilation (<i>n</i> = 210).</p><p><strong>Main outcome measures: </strong>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.</p><p><strong>Results: </strong>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%; <i>p</i> = 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; <i>p</i> = 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 <i>p</i> = 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
{"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":"<p><strong>Background: </strong>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.</p><p><strong>Objective: </strong>To determine whether using extracorporeal carbon dioxide removal improves outcomes in patients with acute hypoxaemic respiratory failure and is cost-effective.</p><p><strong>Design: </strong>A multicentre, randomised, allocation-concealed, open-label, pragmatic clinical trial.</p><p><strong>Setting: </strong>Fifty-one intensive care units across the United Kingdom.</p><p><strong>Participants: </strong>Four hundred and twelve adult patients receiving mechanical ventilation for acute hypoxaemic respiratory failure, of a planned sample size of 1120.</p><p><strong>Interventions: </strong>Lower tidal volume ventilation facilitated by extracorporeal carbon dioxide removal for at least 48 hours (<i>n</i> = 202) or standard care with conventional low tidal volume ventilation (<i>n</i> = 210).</p><p><strong>Main outcome measures: </strong>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.</p><p><strong>Results: </strong>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%; <i>p</i> = 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; <i>p</i> = 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 <i>p</i> = 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}
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
<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
{"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":4.0,"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}
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