Rustam Al-Shahi Salman, Neil Kitchen, Laura Forsyth, Vijeya Ganesan, Peter S Hall, Kirsty Harkness, Peter Ja Hutchinson, Steff C Lewis, Matthias Wr Radatz, Carole Turner, Julia Wade, David Cs White, Philip M White
<p><strong>Background: </strong>The top priority for research into symptomatic cerebral cavernous malformation (also known as brain cavernoma) is whether to have medical management and intervention (using neurosurgical resection or stereotactic radiosurgery) or medical management alone.</p><p><strong>Objectives: </strong>The primary objective was to assess the feasibility of performing a definitive randomised trial addressing this top priority. The secondary objectives were to set up a collaboration involving patient advocacy organisations and clinicians in the United Kingdom and Ireland; perform a QuinteT Recruitment Intervention to identify facilitators and address barriers to recruitment; and conduct a pilot randomised trial with ≈60 participants.</p><p><strong>Design: </strong>Prospective, randomised, open-label, assessor-blinded, parallel-group trial. A mixed-methods QuinteT Recruitment Intervention analysed sites' screening logs and qualitative data from audio-recorded recruitment discussions, interviews with healthcare professionals and patients, investigator workshops and observation of meetings.</p><p><strong>Setting: </strong>Neuroscience hospitals in the United Kingdom and Ireland.</p><p><strong>Participants: </strong>We aimed to recruit ≈60 people of any age, gender and ethnicity who had mental capacity, resided in the United Kingdom/Ireland, and had a brain cavernoma that had caused symptoms due to intracranial haemorrhage, non-haemorrhagic progressive/persistent focal neurological deficit or epileptic seizure(s).</p><p><strong>Interventions: </strong>We identified and addressed barriers and facilitators to optimise informed consent and recruitment. Computerised, web-based randomisation assigned participants (1 : 1) to treatment of their symptomatic brain cavernoma with medical management and intervention (using neurosurgical resection or stereotactic radiosurgery) or medical management alone. Assignment was open to investigators, participants and carers but not clinical outcome event adjudicators.</p><p><strong>Main outcome measures: </strong>Feasibility outcomes included site engagement, recruitment, choice of surgical management, retention, adherence, data quality, clinical outcome event rate and protocol implementation. The primary clinical outcome was symptomatic intracranial haemorrhage or new persistent/progressive non-haemorrhagic focal neurological deficit due to brain cavernoma or intervention during ≥ 6 months of follow-up.</p><p><strong>Results: </strong>Investigators screened 511 patients at 28/40 (70%) sites in the United Kingdom: 322 (63%) eligible, 202 (63%) approached, 96 (48%) uncertain about whether to have intervention and 72 participants [median age was 51 years (interquartile range 39-59), 41 (57%) female, 66 (92%) white, 56 (78%) with prior intracranial haemorrhage and 28 (39%) with prior epileptic seizure] were randomly assigned to medical management and intervention (<i>n</i> = 36; 12 to neurosurgical resecti
{"title":"Medical management and intervention (using neurosurgical resection or stereotactic radiosurgery) versus medical management alone for symptomatic brain cavernoma: the CARE pilot RCT.","authors":"Rustam Al-Shahi Salman, Neil Kitchen, Laura Forsyth, Vijeya Ganesan, Peter S Hall, Kirsty Harkness, Peter Ja Hutchinson, Steff C Lewis, Matthias Wr Radatz, Carole Turner, Julia Wade, David Cs White, Philip M White","doi":"10.3310/GJRS5321","DOIUrl":"10.3310/GJRS5321","url":null,"abstract":"<p><strong>Background: </strong>The top priority for research into symptomatic cerebral cavernous malformation (also known as brain cavernoma) is whether to have medical management and intervention (using neurosurgical resection or stereotactic radiosurgery) or medical management alone.</p><p><strong>Objectives: </strong>The primary objective was to assess the feasibility of performing a definitive randomised trial addressing this top priority. The secondary objectives were to set up a collaboration involving patient advocacy organisations and clinicians in the United Kingdom and Ireland; perform a QuinteT Recruitment Intervention to identify facilitators and address barriers to recruitment; and conduct a pilot randomised trial with ≈60 participants.</p><p><strong>Design: </strong>Prospective, randomised, open-label, assessor-blinded, parallel-group trial. A mixed-methods QuinteT Recruitment Intervention analysed sites' screening logs and qualitative data from audio-recorded recruitment discussions, interviews with healthcare professionals and patients, investigator workshops and observation of meetings.</p><p><strong>Setting: </strong>Neuroscience hospitals in the United Kingdom and Ireland.</p><p><strong>Participants: </strong>We aimed to recruit ≈60 people of any age, gender and ethnicity who had mental capacity, resided in the United Kingdom/Ireland, and had a brain cavernoma that had caused symptoms due to intracranial haemorrhage, non-haemorrhagic progressive/persistent focal neurological deficit or epileptic seizure(s).</p><p><strong>Interventions: </strong>We identified and addressed barriers and facilitators to optimise informed consent and recruitment. Computerised, web-based randomisation assigned participants (1 : 1) to treatment of their symptomatic brain cavernoma with medical management and intervention (using neurosurgical resection or stereotactic radiosurgery) or medical management alone. Assignment was open to investigators, participants and carers but not clinical outcome event adjudicators.</p><p><strong>Main outcome measures: </strong>Feasibility outcomes included site engagement, recruitment, choice of surgical management, retention, adherence, data quality, clinical outcome event rate and protocol implementation. The primary clinical outcome was symptomatic intracranial haemorrhage or new persistent/progressive non-haemorrhagic focal neurological deficit due to brain cavernoma or intervention during ≥ 6 months of follow-up.</p><p><strong>Results: </strong>Investigators screened 511 patients at 28/40 (70%) sites in the United Kingdom: 322 (63%) eligible, 202 (63%) approached, 96 (48%) uncertain about whether to have intervention and 72 participants [median age was 51 years (interquartile range 39-59), 41 (57%) female, 66 (92%) white, 56 (78%) with prior intracranial haemorrhage and 28 (39%) with prior epileptic seizure] were randomly assigned to medical management and intervention (<i>n</i> = 36; 12 to neurosurgical resecti","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":"29 38","pages":"1-24"},"PeriodicalIF":4.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12376205/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144872834","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}
Jeremy Howick, Martina Svobodova, Shaun Treweek, Katie Gillies, Adrian Edwards, Peter Bower, Jennifer Bostock, Nina Jacob, Kerenza Hood
Background: Variation in the way information about potential trial intervention benefits and harms is conveyed within patient information leaflets can cause avoidable information-induced ('nocebo') harm, research waste, and may be unethical.
Objectives: 1. To develop stakeholder-informed principles to guide how to describe information about potential trial intervention benefits and harms within patient information leaflets. 2. To test whether using these principles are feasible for testing in trials that measure whether they improve recruitment and adverse event rates. 3. To develop and disseminate guidance on how to implement the principles.
Methods: We used a mixed methodology consisting of three work packages. Work package 1 involved a modified Delphi survey and consensus meeting to develop the principles for harmonising the way information regarding potential benefits and harms are shared. Work package 2 involved testing whether the principles could be used to transform existing patient information leaflets by recruiting host trials to compare standard patient information leaflets with patient information leaflets developed using the principles 'principled patient information leaflets'. We also set up an infrastructure to test whether they could reduce variation, impact trial recruitment and reduce reported adverse events. Work package 3 involved developing and disseminating guidance for using the principles.
Results: For work package 1, 250 participants completed the Delphi survey and 7 principles were agreed upon: (1) all potential intervention harms should be listed, (2) potential harms should be separated into 'serious' and 'less serious', (3) if not all potential harms are known, this needs to be explicitly stated, (4) all potential benefits should be listed, (5) potential benefits and harms associated with trial participation need to be compared with those associated with non-participation, (6) suitable visual representations should be added where appropriate, and (7) information about potential benefits and harms should not be separated by more than one page. For work package 2, we developed principled patient information leaflets for five host trials and interviewed two members of each host trial team. Two host trials agreed to compare the patient information leaflets with principled patient information leaflets using Studies Within a Trial, and we published a protocol for a meta-analysis that will synthesise the results. For work package 3, 25 participants attended a hybrid workshop and recommended that researchers and Research Ethics Committee members should use the principles to design and evaluate patient information leaflets. We produced a guidance booklet and website, which are currently being used by some Health Research Authority Research Ethics Committees.
Conclusions: A strong consensus was reached regarding seven
{"title":"Developing evidence-based guidelines for describing potential benefits and harms within patient information leaflets/sheets (PILs) that inform and do not cause harm (PrinciPILs).","authors":"Jeremy Howick, Martina Svobodova, Shaun Treweek, Katie Gillies, Adrian Edwards, Peter Bower, Jennifer Bostock, Nina Jacob, Kerenza Hood","doi":"10.3310/GJJH2402","DOIUrl":"10.3310/GJJH2402","url":null,"abstract":"<p><strong>Background: </strong>Variation in the way information about potential trial intervention benefits and harms is conveyed within patient information leaflets can cause avoidable information-induced ('nocebo') harm, research waste, and may be unethical.</p><p><strong>Objectives: </strong>1. To develop stakeholder-informed principles to guide how to describe information about potential trial intervention benefits and harms within patient information leaflets. 2. To test whether using these principles are feasible for testing in trials that measure whether they improve recruitment and adverse event rates. 3. To develop and disseminate guidance on how to implement the principles.</p><p><strong>Methods: </strong>We used a mixed methodology consisting of three work packages. Work package 1 involved a modified Delphi survey and consensus meeting to develop the principles for harmonising the way information regarding potential benefits and harms are shared. Work package 2 involved testing whether the principles could be used to transform existing patient information leaflets by recruiting host trials to compare standard patient information leaflets with patient information leaflets developed using the principles 'principled patient information leaflets'. We also set up an infrastructure to test whether they could reduce variation, impact trial recruitment and reduce reported adverse events. Work package 3 involved developing and disseminating guidance for using the principles.</p><p><strong>Results: </strong>For work package 1, 250 participants completed the Delphi survey and 7 principles were agreed upon: (1) all potential intervention harms should be listed, (2) potential harms should be separated into 'serious' and 'less serious', (3) if not all potential harms are known, this needs to be explicitly stated, (4) all potential benefits should be listed, (5) potential benefits and harms associated with trial participation need to be compared with those associated with non-participation, (6) suitable visual representations should be added where appropriate, and (7) information about potential benefits and harms should not be separated by more than one page. For work package 2, we developed principled patient information leaflets for five host trials and interviewed two members of each host trial team. Two host trials agreed to compare the patient information leaflets with principled patient information leaflets using Studies Within a Trial, and we published a protocol for a meta-analysis that will synthesise the results. For work package 3, 25 participants attended a hybrid workshop and recommended that researchers and Research Ethics Committee members should use the principles to design and evaluate patient information leaflets. We produced a guidance booklet and website, which are currently being used by some Health Research Authority Research Ethics Committees.</p><p><strong>Conclusions: </strong>A strong consensus was reached regarding seven ","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":"29 43","pages":"1-20"},"PeriodicalIF":4.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12434871/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144951732","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}
C J Hawkey, Anthony J Avery, Carol Ac Coupland, Colin J Crooks, Jennifer S Dumbleton, Fd Richard Hobbs, Denise Kendrick, Michael Moore, Clive Morris, Gregory Rubin, Murray Smith, Diane Stevenson
Background: Peptic ulcers in patients on aspirin are associated with Helicobacter pylori infection. We investigated whether H. pylori eradication would protect against aspirin-associated ulcer bleeding.
Methods: The Helicobacter Eradication Aspirin Trial was a randomised placebo-controlled trial (European Union Drug Regulating Authorities Clinical Trials 2011-003425-96), conducted in United Kingdom primary care using routinely collected clinical data. Consenting participants aged ≥ 60 years prescribed aspirin ≤ 325 mg but not ulcerogenic or gastroprotective medication underwent C13 urea breath testing for H. pylori. Those with a positive test were randomised to receive either a combination of clarithromycin 500 mg, metronidazole 400 mg and lansoprazole 30 mg, or placebos twice daily for 7 days. The primary outcome, time to death or hospitalisation due to peptic ulcer bleeding, was analysed using a Cox proportional hazards model.
Findings: Between 14 September 2012 and 22 November 2017, 30,166 participants underwent H. pylori breath testing, 5367 had a positive result, 5352 were randomised to an intention-to-treat population of 2677 (eradication) and 2675 (placebo) and followed up for a median of 5.0 years (interquartile range 3.9-6.4). Statistical analysis of the primary outcome showed an overall hazard ratio of 0.69 [95% confidence interval 0.38 to 1.25; p = 0.22], but there was a significant departure from the proportional hazards assumption (p = 0.0068), requiring analysis split at the median time to event: 2.5 years. There was a significant reduction in the primary outcome in the eradication treatment group in the first 2.5 years (hazard ratio 0.35, 95% confidence interval 0.14 to 0.89; p = 0.028) but not the second period (hazard ratio 1.31, 95% confidence interval 0.55 to 3.11). The number needed to treat (first period) was 238 (95% confidence interval 184 to 1661). Results in the first 2.5 years remained significant when accounting for the competing risk of death (p = 0.028). During the study period, 657 participants died (306 in the eradication group and 351 in the controls group; hazard ratio 0.86, 95% confidence interval 0.74 to 1.01; p = 0.058). Malignancy was the most common cause of death and largely accounted for the numerical difference between the treatment groups. A health economic analysis found proactive screening not cost-effective, since the monetised benefits of the intervention in preventing a peptic ulcer bleed failed to outweigh the costs.
Interpretation: Helicobacter pylori eradication protects against aspirin-associated peptic ulcer bleeding, but this may not be sustained or cost-effective when applied non-selectively to our study population. The possibility that H. pylori eradication, on a background of aspirin use, might affect death from malignanc
{"title":"Eradication of <i>Helicobacter pylori</i> for prevention of aspirin-associated peptic ulcer bleeding in adults over 65 years: the HEAT RCT.","authors":"C J Hawkey, Anthony J Avery, Carol Ac Coupland, Colin J Crooks, Jennifer S Dumbleton, Fd Richard Hobbs, Denise Kendrick, Michael Moore, Clive Morris, Gregory Rubin, Murray Smith, Diane Stevenson","doi":"10.3310/LLKF7871","DOIUrl":"10.3310/LLKF7871","url":null,"abstract":"<p><strong>Background: </strong>Peptic ulcers in patients on aspirin are associated with <i>Helicobacter pylori</i> infection. We investigated whether <i>H. pylori</i> eradication would protect against aspirin-associated ulcer bleeding.</p><p><strong>Methods: </strong>The <i>Helicobacter</i> Eradication Aspirin Trial was a randomised placebo-controlled trial (European Union Drug Regulating Authorities Clinical Trials 2011-003425-96), conducted in United Kingdom primary care using routinely collected clinical data. Consenting participants aged ≥ 60 years prescribed aspirin ≤ 325 mg but not ulcerogenic or gastroprotective medication underwent C13 urea breath testing for <i>H. pylori</i>. Those with a positive test were randomised to receive either a combination of clarithromycin 500 mg, metronidazole 400 mg and lansoprazole 30 mg, or placebos twice daily for 7 days. The primary outcome, time to death or hospitalisation due to peptic ulcer bleeding, was analysed using a Cox proportional hazards model.</p><p><strong>Findings: </strong>Between 14 September 2012 and 22 November 2017, 30,166 participants underwent <i>H. pylori</i> breath testing, 5367 had a positive result, 5352 were randomised to an intention-to-treat population of 2677 (eradication) and 2675 (placebo) and followed up for a median of 5.0 years (interquartile range 3.9-6.4). Statistical analysis of the primary outcome showed an overall hazard ratio of 0.69 [95% confidence interval 0.38 to 1.25; <i>p</i> = 0.22], but there was a significant departure from the proportional hazards assumption (<i>p</i> = 0.0068), requiring analysis split at the median time to event: 2.5 years. There was a significant reduction in the primary outcome in the eradication treatment group in the first 2.5 years (hazard ratio 0.35, 95% confidence interval 0.14 to 0.89; <i>p</i> = 0.028) but not the second period (hazard ratio 1.31, 95% confidence interval 0.55 to 3.11). The number needed to treat (first period) was 238 (95% confidence interval 184 to 1661). Results in the first 2.5 years remained significant when accounting for the competing risk of death (<i>p</i> = 0.028). During the study period, 657 participants died (306 in the eradication group and 351 in the controls group; hazard ratio 0.86, 95% confidence interval 0.74 to 1.01; <i>p</i> = 0.058). Malignancy was the most common cause of death and largely accounted for the numerical difference between the treatment groups. A health economic analysis found proactive screening not cost-effective, since the monetised benefits of the intervention in preventing a peptic ulcer bleed failed to outweigh the costs.</p><p><strong>Interpretation: </strong><i>Helicobacter pylori</i> eradication protects against aspirin-associated peptic ulcer bleeding, but this may not be sustained or cost-effective when applied non-selectively to our study population. The possibility that <i>H. pylori</i> eradication, on a background of aspirin use, might affect death from malignanc","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":"29 42","pages":"1-62"},"PeriodicalIF":4.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12434569/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144951691","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}
Rachel L Adams, Alisha Maher, Nicola Gale, Anjali Crawshaw, David Thickett, Alice M Turner
<p><strong>Introduction: </strong>Idiopathic pulmonary fibrosis is a devastating condition of unknown cause that results in progressive, irreversible scarring of the lung, manifesting as breathlessness and dry cough. Idiopathic pulmonary fibrosis is thought to be responsible for as many as 1 in 100 deaths in the United Kingdom, killing 5300 people a year. Ambulatory oxygen therapy is commonly used in idiopathic pulmonary fibrosis to relieve exertional breathlessness, although evidence to support this strategy is lacking. This pragmatic randomised controlled trial was planned to test whether use of ambulatory oxygen therapy is beneficial in people with idiopathic pulmonary fibrosis.</p><p><strong>Methods: </strong>We planned a randomised controlled trial in 260 patients with idiopathic pulmonary fibrosis who are breathless on exertion and do not meet criteria for long-term oxygen therapy, randomising in a 1 : 1 ratio between ambulatory oxygen therapy and best supportive care. Primary outcome was a quality-of-life questionnaire validated in pulmonary fibrosis, the King's Brief Interstitial Lung Disease questionnaire, measured at 6 months. We calculated our sample size based on the minimum clinically important difference of four units and standard deviation equal to 8.85 in King's Brief Interstitial Lung Disease questionnaire; assuming power of 90% and 5% two-sided significance level, thus required 130 per arm, after accounting for 20% dropout. The trials unit's web-based randomisation algorithm minimises on factors potentially influencing response to ambulatory oxygen therapy, such as severity of idiopathic pulmonary fibrosis, desaturation to < 88% present on walking, current or recent (within 6 months) pulmonary rehabilitation, and recruitment centre. Secondary outcomes included symptoms, exercise capacity and cost-effectiveness. A process evaluation included assessment of trial fidelity and acceptability of the intervention with use of qualitative research methods and arts approaches with patients and staff. Qualitative interviews were conducted with patients from the Ambulatory Oxygen for Pulmonary Fibrosis trial and the idiopathic pulmonary fibrosis patient support group Action for Pulmonary Fibrosis, and stakeholders: healthcare professionals and policy-makers. Interviews were audio-recorded, transcribed clean verbatim. Photovoice methodology was conducted with patients. A workshop prior to data collection informed and guided data collection and analysis. Traditional qualitative analysis and arts-based coproduction analysis approaches were used to produce a short film. An economic model was planned but could not occur due to early termination.</p><p><strong>Results: </strong>The trial was stopped prematurely due to low recruitment. This was due to a combination of the impact of COVID-19 on research infrastructure, financial issues for sites with the payment structure for the trial and lack of equipoise which limited site recruitment. Seven out
{"title":"Ambulatory Oxygen for Pulmonary Fibrosis (OxyPuF): a randomised controlled trial and acceptability study.","authors":"Rachel L Adams, Alisha Maher, Nicola Gale, Anjali Crawshaw, David Thickett, Alice M Turner","doi":"10.3310/TWKS4194","DOIUrl":"10.3310/TWKS4194","url":null,"abstract":"<p><strong>Introduction: </strong>Idiopathic pulmonary fibrosis is a devastating condition of unknown cause that results in progressive, irreversible scarring of the lung, manifesting as breathlessness and dry cough. Idiopathic pulmonary fibrosis is thought to be responsible for as many as 1 in 100 deaths in the United Kingdom, killing 5300 people a year. Ambulatory oxygen therapy is commonly used in idiopathic pulmonary fibrosis to relieve exertional breathlessness, although evidence to support this strategy is lacking. This pragmatic randomised controlled trial was planned to test whether use of ambulatory oxygen therapy is beneficial in people with idiopathic pulmonary fibrosis.</p><p><strong>Methods: </strong>We planned a randomised controlled trial in 260 patients with idiopathic pulmonary fibrosis who are breathless on exertion and do not meet criteria for long-term oxygen therapy, randomising in a 1 : 1 ratio between ambulatory oxygen therapy and best supportive care. Primary outcome was a quality-of-life questionnaire validated in pulmonary fibrosis, the King's Brief Interstitial Lung Disease questionnaire, measured at 6 months. We calculated our sample size based on the minimum clinically important difference of four units and standard deviation equal to 8.85 in King's Brief Interstitial Lung Disease questionnaire; assuming power of 90% and 5% two-sided significance level, thus required 130 per arm, after accounting for 20% dropout. The trials unit's web-based randomisation algorithm minimises on factors potentially influencing response to ambulatory oxygen therapy, such as severity of idiopathic pulmonary fibrosis, desaturation to < 88% present on walking, current or recent (within 6 months) pulmonary rehabilitation, and recruitment centre. Secondary outcomes included symptoms, exercise capacity and cost-effectiveness. A process evaluation included assessment of trial fidelity and acceptability of the intervention with use of qualitative research methods and arts approaches with patients and staff. Qualitative interviews were conducted with patients from the Ambulatory Oxygen for Pulmonary Fibrosis trial and the idiopathic pulmonary fibrosis patient support group Action for Pulmonary Fibrosis, and stakeholders: healthcare professionals and policy-makers. Interviews were audio-recorded, transcribed clean verbatim. Photovoice methodology was conducted with patients. A workshop prior to data collection informed and guided data collection and analysis. Traditional qualitative analysis and arts-based coproduction analysis approaches were used to produce a short film. An economic model was planned but could not occur due to early termination.</p><p><strong>Results: </strong>The trial was stopped prematurely due to low recruitment. This was due to a combination of the impact of COVID-19 on research infrastructure, financial issues for sites with the payment structure for the trial and lack of equipoise which limited site recruitment. Seven out","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":" ","pages":"1-33"},"PeriodicalIF":4.0,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12376201/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560001","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}
Background: Recurrence or persistence of symptoms after interventions to treat stress urinary incontinence in women is common, but without robust evidence to base treatment recommendations.
Objectives: To investigate whether endoscopic or surgical treatments for stress urinary incontinence in women are effective and cost-effective.
Design: A multicentre, unblinded, parallel-group randomised controlled trial.
Setting: Fifteen centres across the United Kingdom.
Participants: Adult women with recurrent or persistent stress urinary incontinence.
Intervention: Individual randomisation to endoscopic (urethral bulking) or surgical (autologous sling, colposuspension, artificial urinary sphincter) interventions. Women randomised to surgery chose their operative intervention.
Main outcomes: Primary outcome self-reported International Consultation on Incontinence Questionnaire-Urinary Incontinence-Short Form at 1 year post randomisation. Secondary outcomes included International Consultation on Incontinence Questionnaire-Urinary Incontinence-Short Form, Patient Global Impression of Improvement and Pelvic Organ Prolapse/Urinary Incontinence Sexual questionnaires up to 3 years post randomisation, operative assessment measures and adverse events, cost-effectiveness from National Health Service and societal perspectives (quality-adjusted life-years and International Consultation on Incontinence Questionnaire-Urinary Incontinence-Short Form) at 1 year, and a secondary care perspective (quality-adjusted life-years) at 3 years. Semistructured qualitative interviews at baseline (post randomisation), follow-up (3-6 months) and longer-term (12 and 36 months), to explore stress urinary incontinence generally, the acceptability and attitudes to treatments and to improve understanding of outcomes. Qualitative interviews with clinicians at baseline were focused on potential difficulties of recruitment and optimising patient-facing information and training materials for clinicians.
Results: Fifty-five women were deemed eligible after screening (n = 328 screened) from October 2019 to June 2022. Twenty-four eligible women consented, and 23 were randomised (between January 2020 and July 2022) from 8 sites with the average age of 57 years (standard deviation: 10.7) and all self-reported 'white' ethnicity. Participants reported a median International Consultation on Incontinence Questionnaire-Urinary Incontinence-Short Form score at baseline of 16 (interquartile range: 13-19) and mean post-void residual volume of 4.64 ml (standard deviation: 8.45). Eleven participants received their allocated intervention, 2 participants withdrew prior to receiving their intervention and 10 were waiting for their intervention when the study closed. The most common reason for declining participation was a trea
{"title":"Challenges to overcome in a randomised trial for Proper Understanding of Recurrent Stress Urinary Incontinence Treatment in women: the PURSUIT RCT.","authors":"Caroline Pope, Madeleine Cochrane, Clare Clement, Yumeng Liu, Sangeetha Paramasivan, Sian Noble, Stephanie J MacNeill, Amanda L Lewis, Jodi Taylor, Bethanie Fitzgerald, Nikki Cotterill, Tamsin Greenwell, Hashim Hashim, Swati Jha, Nikesh Thiruchelvam, Philip Toozs-Hobson, Alison White, Wael Agur, J Athene Lane, Marcus Drake","doi":"10.3310/AKAK8992","DOIUrl":"10.3310/AKAK8992","url":null,"abstract":"<p><strong>Background: </strong>Recurrence or persistence of symptoms after interventions to treat stress urinary incontinence in women is common, but without robust evidence to base treatment recommendations.</p><p><strong>Objectives: </strong>To investigate whether endoscopic or surgical treatments for stress urinary incontinence in women are effective and cost-effective.</p><p><strong>Design: </strong>A multicentre, unblinded, parallel-group randomised controlled trial.</p><p><strong>Setting: </strong>Fifteen centres across the United Kingdom.</p><p><strong>Participants: </strong>Adult women with recurrent or persistent stress urinary incontinence.</p><p><strong>Intervention: </strong>Individual randomisation to endoscopic (urethral bulking) or surgical (autologous sling, colposuspension, artificial urinary sphincter) interventions. Women randomised to surgery chose their operative intervention.</p><p><strong>Main outcomes: </strong>Primary outcome self-reported International Consultation on Incontinence Questionnaire-Urinary Incontinence-Short Form at 1 year post randomisation. Secondary outcomes included International Consultation on Incontinence Questionnaire-Urinary Incontinence-Short Form, Patient Global Impression of Improvement and Pelvic Organ Prolapse/Urinary Incontinence Sexual questionnaires up to 3 years post randomisation, operative assessment measures and adverse events, cost-effectiveness from National Health Service and societal perspectives (quality-adjusted life-years and International Consultation on Incontinence Questionnaire-Urinary Incontinence-Short Form) at 1 year, and a secondary care perspective (quality-adjusted life-years) at 3 years. Semistructured qualitative interviews at baseline (post randomisation), follow-up (3-6 months) and longer-term (12 and 36 months), to explore stress urinary incontinence generally, the acceptability and attitudes to treatments and to improve understanding of outcomes. Qualitative interviews with clinicians at baseline were focused on potential difficulties of recruitment and optimising patient-facing information and training materials for clinicians.</p><p><strong>Results: </strong>Fifty-five women were deemed eligible after screening (<i>n</i> = 328 screened) from October 2019 to June 2022. Twenty-four eligible women consented, and 23 were randomised (between January 2020 and July 2022) from 8 sites with the average age of 57 years (standard deviation: 10.7) and all self-reported 'white' ethnicity. Participants reported a median International Consultation on Incontinence Questionnaire-Urinary Incontinence-Short Form score at baseline of 16 (interquartile range: 13-19) and mean post-void residual volume of 4.64 ml (standard deviation: 8.45). Eleven participants received their allocated intervention, 2 participants withdrew prior to receiving their intervention and 10 were waiting for their intervention when the study closed. The most common reason for declining participation was a trea","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":" ","pages":"1-43"},"PeriodicalIF":4.0,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12376003/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560002","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}
Glenn Nielsen, Louise Marston, Rachael Maree Hunter, Alan Carson, Laura H Goldstein, Kate Holt, Teresa C Lee, Marie Le Novere, Jonathan Marsden, Irwin Nazareth, Hayley Noble, Markus Reuber, Jon Stone, Ann-Marie Strudwick, Beatriz Santana Suarez, Mark J Edwards
<p><strong>Background: </strong>Functional motor disorder often causes persistent disabling symptoms that are associated with high healthcare costs. In recent years, specialist physiotherapy, informed by an understanding of functional motor disorder, has emerged as a promising treatment, but there is an absence of evidence of its effectiveness from large randomised controlled trials.</p><p><strong>Methods: </strong>We conducted a pragmatic, multicentre, randomised controlled trial, comparing specialist physiotherapy for functional motor disorder to treatment as usual, which was defined as community neurological physiotherapy. The primary outcome was the Short Form questionnaire-36 items Physical Functioning domain at 12 months (scale range 0-100, with 100 indicating optimum health). The trial was powered to detect a 9-point difference in the primary outcome with 90% power at the 5% level of significance. Secondary domains of measurement included a patient perception of improvement, health-related quality of life, mobility, anxiety, depression and illness perception. We also completed a health economic analysis with the primary aim of calculating the mean incremental cost per quality-adjusted life-year over 12 months. In prespecified analysis plans, we excluded participants from the primary analysis if they were unable to receive their trial-allocated treatment due to COVID-19 lockdown restrictions. Sensitivity analysis explored the impact of this decision.</p><p><strong>Results: </strong>Between 19 October 2018 and 31 January 2022, 355 adults with functional motor disorder were randomised (1 : 1) to specialist physiotherapy (<i>n</i> = 179) and treatment as usual (<i>n</i> = 176). Eighty-nine participants were excluded due to COVID-19 disruptions. Retention for the primary analysis was 90% for both groups, leaving 241 participants in the primary analysis. At 12 months, there was no between-group difference in the primary outcome (adjusted mean difference 3.5, 95% confidence interval -2.3 to 9.3). However, several secondary outcomes favoured specialist physiotherapy, including the participant perception of improvement, Short Form questionnaire-36 items Mental Health domain, confidence in the diagnosis and two subscales (Personal Control and Illness Coherence) of the Revised Illness Perception Questionnaire. There were no differences in the remaining outcomes. At 6 months, the following outcome measures were significantly different, in favour of specialist physiotherapy: participant perception of improvement, the Short Form questionnaire-36 items Physical Role Limitations, Short Form questionnaire-36 items Social Functioning, Short Form questionnaire-36 items Mental Health, EuroQol-5 Dimensions five-level version utility score, confidence in the diagnosis and three subscales (Timeline Cyclical, Personal Control and Treatment Control) of the Revised Illness Perception Questionnaire. No outcomes significantly favoured treatment as usual. In the healt
{"title":"Outcomes of specialist physiotherapy for functional motor disorder: the Physio4FMD RCT.","authors":"Glenn Nielsen, Louise Marston, Rachael Maree Hunter, Alan Carson, Laura H Goldstein, Kate Holt, Teresa C Lee, Marie Le Novere, Jonathan Marsden, Irwin Nazareth, Hayley Noble, Markus Reuber, Jon Stone, Ann-Marie Strudwick, Beatriz Santana Suarez, Mark J Edwards","doi":"10.3310/MKAC9495","DOIUrl":"10.3310/MKAC9495","url":null,"abstract":"<p><strong>Background: </strong>Functional motor disorder often causes persistent disabling symptoms that are associated with high healthcare costs. In recent years, specialist physiotherapy, informed by an understanding of functional motor disorder, has emerged as a promising treatment, but there is an absence of evidence of its effectiveness from large randomised controlled trials.</p><p><strong>Methods: </strong>We conducted a pragmatic, multicentre, randomised controlled trial, comparing specialist physiotherapy for functional motor disorder to treatment as usual, which was defined as community neurological physiotherapy. The primary outcome was the Short Form questionnaire-36 items Physical Functioning domain at 12 months (scale range 0-100, with 100 indicating optimum health). The trial was powered to detect a 9-point difference in the primary outcome with 90% power at the 5% level of significance. Secondary domains of measurement included a patient perception of improvement, health-related quality of life, mobility, anxiety, depression and illness perception. We also completed a health economic analysis with the primary aim of calculating the mean incremental cost per quality-adjusted life-year over 12 months. In prespecified analysis plans, we excluded participants from the primary analysis if they were unable to receive their trial-allocated treatment due to COVID-19 lockdown restrictions. Sensitivity analysis explored the impact of this decision.</p><p><strong>Results: </strong>Between 19 October 2018 and 31 January 2022, 355 adults with functional motor disorder were randomised (1 : 1) to specialist physiotherapy (<i>n</i> = 179) and treatment as usual (<i>n</i> = 176). Eighty-nine participants were excluded due to COVID-19 disruptions. Retention for the primary analysis was 90% for both groups, leaving 241 participants in the primary analysis. At 12 months, there was no between-group difference in the primary outcome (adjusted mean difference 3.5, 95% confidence interval -2.3 to 9.3). However, several secondary outcomes favoured specialist physiotherapy, including the participant perception of improvement, Short Form questionnaire-36 items Mental Health domain, confidence in the diagnosis and two subscales (Personal Control and Illness Coherence) of the Revised Illness Perception Questionnaire. There were no differences in the remaining outcomes. At 6 months, the following outcome measures were significantly different, in favour of specialist physiotherapy: participant perception of improvement, the Short Form questionnaire-36 items Physical Role Limitations, Short Form questionnaire-36 items Social Functioning, Short Form questionnaire-36 items Mental Health, EuroQol-5 Dimensions five-level version utility score, confidence in the diagnosis and three subscales (Timeline Cyclical, Personal Control and Treatment Control) of the Revised Illness Perception Questionnaire. No outcomes significantly favoured treatment as usual. In the healt","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":"29 34","pages":"1-28"},"PeriodicalIF":4.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12376006/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144775304","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}
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}
Janet Treasure, Katie Rowlands, Valentina Cardi, Suman Ambwani, David McDaid, Jodie Lord, Danielle Clark Bryan, Pamela Macdonald, Eva Bonin, Ulrike Schmidt, Jon Arcelus, Amy Harrison, Sabine Landau
<p><strong>Background: </strong>High-risk patients with complex anorexia nervosa are managed in inpatient/day patient care, but re-admission rates are high, and new treatments are needed.</p><p><strong>Objective(s): </strong>To examine the effectiveness of a digital augmentation of aftercare (ECHOMANTRA).</p><p><strong>Design: </strong>Transition Care In Anorexia Nervosa through Guidance Online from Peer and Carer Expertise was a multicentre, parallel-group, superiority randomised controlled trial. ECHOMANTRA augmented treatment as usual was compared with treatment as usual. Patient-carer dyads were randomised using minimisation on a 1 : 1 ratio into ECHOMANTRA + treatment as usual (ECHOMANTRA) or treatment as usual alone.</p><p><strong>Setting: </strong>Specialised United Kingdom inpatient/day patient sites (<i>n</i> = 31) participated.</p><p><strong>Participants: </strong>Patient-carer dyads were randomised (<i>n</i> = 185 in ECHOMANTRA and <i>n</i> = 186 in treatment as usual).</p><p><strong>Interventions: </strong>The digital ECHOMANTRA intervention included self-management tools (recovery tips videos) for patients and task-sharing materials for carers (skill-sharing video), supplemented with guided group chat sessions. All participants randomised to ECHOMANTRA + treatment as usual had access to the psychoeducational materials and joint patient/carer chat sessions were also offered.</p><p><strong>Main outcome measures: </strong>The primary outcome was patient distress at 12 months. Other outcomes included patient distress at 18 months, and eating disorder symptoms, social and work adjustment, and carer distress and skills at 12 and 18 months.</p><p><strong>Results: </strong>There was no evidence of an intervention effect on the Depression Anxiety Stress Scale-21 outcome for patients (<i>n</i> = 370) at 12 months, estimated effect 0.48, 95% confidence interval -0.20 to 0.23, standardised estimate (0.02, <i>p</i> = 0.87). In the economic analysis, the intervention was dominated by treatment as usual from both a health system and wider societal perspective, as ECHOMANTRA cost more and resulted in fewer quality-adjusted life-years gained. However, the uptake of the interactive component of the intervention (i.e. the facilitated and moderated online groups) was limited, with only 20% of the dyad members attending the pre-set minimal adherence level (i.e. both the patient and carer attending at least four online forum group sessions). The feedback about the intervention was predominantly positive. For example, the group facilitators were rated highly. However, some feedback was that the intervention offered too little, too late, and that a more personalised intervention would be more helpful.</p><p><strong>Limitations: </strong>Participants were diverse (e.g. 20% were being treated under the Mental Health Act), and a large proportion had a range of comorbidities (depression, anxiety, obsessive-compulsive disorder and autistic spectrum disorders), a
{"title":"Digital augmentation of aftercare for patients with anorexia nervosa: the TRIANGLE RCT and economic evaluation.","authors":"Janet Treasure, Katie Rowlands, Valentina Cardi, Suman Ambwani, David McDaid, Jodie Lord, Danielle Clark Bryan, Pamela Macdonald, Eva Bonin, Ulrike Schmidt, Jon Arcelus, Amy Harrison, Sabine Landau","doi":"10.3310/ADLS3672","DOIUrl":"10.3310/ADLS3672","url":null,"abstract":"<p><strong>Background: </strong>High-risk patients with complex anorexia nervosa are managed in inpatient/day patient care, but re-admission rates are high, and new treatments are needed.</p><p><strong>Objective(s): </strong>To examine the effectiveness of a digital augmentation of aftercare (ECHOMANTRA).</p><p><strong>Design: </strong>Transition Care In Anorexia Nervosa through Guidance Online from Peer and Carer Expertise was a multicentre, parallel-group, superiority randomised controlled trial. ECHOMANTRA augmented treatment as usual was compared with treatment as usual. Patient-carer dyads were randomised using minimisation on a 1 : 1 ratio into ECHOMANTRA + treatment as usual (ECHOMANTRA) or treatment as usual alone.</p><p><strong>Setting: </strong>Specialised United Kingdom inpatient/day patient sites (<i>n</i> = 31) participated.</p><p><strong>Participants: </strong>Patient-carer dyads were randomised (<i>n</i> = 185 in ECHOMANTRA and <i>n</i> = 186 in treatment as usual).</p><p><strong>Interventions: </strong>The digital ECHOMANTRA intervention included self-management tools (recovery tips videos) for patients and task-sharing materials for carers (skill-sharing video), supplemented with guided group chat sessions. All participants randomised to ECHOMANTRA + treatment as usual had access to the psychoeducational materials and joint patient/carer chat sessions were also offered.</p><p><strong>Main outcome measures: </strong>The primary outcome was patient distress at 12 months. Other outcomes included patient distress at 18 months, and eating disorder symptoms, social and work adjustment, and carer distress and skills at 12 and 18 months.</p><p><strong>Results: </strong>There was no evidence of an intervention effect on the Depression Anxiety Stress Scale-21 outcome for patients (<i>n</i> = 370) at 12 months, estimated effect 0.48, 95% confidence interval -0.20 to 0.23, standardised estimate (0.02, <i>p</i> = 0.87). In the economic analysis, the intervention was dominated by treatment as usual from both a health system and wider societal perspective, as ECHOMANTRA cost more and resulted in fewer quality-adjusted life-years gained. However, the uptake of the interactive component of the intervention (i.e. the facilitated and moderated online groups) was limited, with only 20% of the dyad members attending the pre-set minimal adherence level (i.e. both the patient and carer attending at least four online forum group sessions). The feedback about the intervention was predominantly positive. For example, the group facilitators were rated highly. However, some feedback was that the intervention offered too little, too late, and that a more personalised intervention would be more helpful.</p><p><strong>Limitations: </strong>Participants were diverse (e.g. 20% were being treated under the Mental Health Act), and a large proportion had a range of comorbidities (depression, anxiety, obsessive-compulsive disorder and autistic spectrum disorders), a","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":"29 31","pages":"1-162"},"PeriodicalIF":4.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12336943/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144682462","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":4.0,"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":4.0,"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}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：