Mostafa Metwally, Kirsty McKendrick, Katie Ridsdale, Clare Pye, Stephen Walters, Saad Amer, Amy Barr, Robin Chatters, Ying Cheong, Meenakshi Choudhary, Mary Connor, Lauren Desoysa, Tarek El-Toukhy, Anju Keetharuth, Nick Latimer, Amanda Loban, Lamiya Mohiyiddeen, Mohamed Mostafa, Clair Scaife, Tony Stone, Liz Taylor, Chris Turtle, David White
<p><strong>Background: </strong>Infertility affects one in six of females globally, with uterine submucous fibroids and endometrial polyps being common findings. The effectiveness of surgical removal to improve fertility remains uncertain. The associated surgical risks and costs highlight the need for more robust research in this area. The HELP Fertility? Study aimed to assess the clinical and cost-effectiveness of hysteroscopic removal of endometrial polyps and submucosal fibroids, compared to no removal, in improving fertility outcomes for participants with infertility or recurrent miscarriage while also evaluating participant experience and longer-term effects. The trial was designed as a multicentre, pragmatic superiority randomised controlled trial with two concurrent trials; one for endometrial polyps and one for submucosal fibroids, with a 9-month feasibility pilot. Participants were randomly assigned 1 : 1 to either receive hysteroscopic resection or no resection. The primary outcome was live birth rate at 15 months. Secondary outcomes included pregnancy rates, procedure details, patient satisfaction and resource use.</p><p><strong>Results: </strong>COVID-19 resulted in significant recruitment challenges, with delays in site set-up and participant enrolment due to pandemic-related healthcare disruptions. The trial was closed early by the National Institute for Health and Care Research-Health Technology Assessment programme following recruitment of 35 participants (19 hysteroscopic resection and 16 no resection) out of a target of 1120. The clinical and cost-effectiveness analyses were severely limited by the small sample size. Clinical pregnancy rates within 15 months of randomisation were 26.5% (5/19) in the hysteroscopic resection group and were 37.5% (6/16) in the no resection group. The live birth rate within 15 months of randomisation (the primary outcome) were 15.8% (3/19) in the hysteroscopic resection group and 18.8% (3/16) in the no resection group: a risk difference of -3.0% (95% confidence intervals -31.1% to 24.2%). No serious adverse events were observed in the follow-up. At the mean, hysteroscopic resection resulted in fewer live births, but increased costs, implying that resection is not cost-effective compared to no resection. However, results were highly uncertain and confidence intervals for incremental costs and the incremental live birth rate spanned zero. At a cost-effectiveness threshold of £20,000 per additional live birth, there is a 10% probability that hysteroscopic resection represents a cost-effective intervention and a 90% probability that no resection is cost-effective. There is a 56% probability that resection is more costly and less effective than no resection. Despite implementing remote training, centralised support and opening 16 National Health Service sites by February 2023, insufficient participants were recruited within planned time frames. The study was ultimately closed as part of the NIHR Research
{"title":"Removal of small fibroids and polyps in patients with infertility and recurrent miscarriage: The HELP Fertility? RCT.","authors":"Mostafa Metwally, Kirsty McKendrick, Katie Ridsdale, Clare Pye, Stephen Walters, Saad Amer, Amy Barr, Robin Chatters, Ying Cheong, Meenakshi Choudhary, Mary Connor, Lauren Desoysa, Tarek El-Toukhy, Anju Keetharuth, Nick Latimer, Amanda Loban, Lamiya Mohiyiddeen, Mohamed Mostafa, Clair Scaife, Tony Stone, Liz Taylor, Chris Turtle, David White","doi":"10.3310/GJMM1915","DOIUrl":"10.3310/GJMM1915","url":null,"abstract":"<p><strong>Background: </strong>Infertility affects one in six of females globally, with uterine submucous fibroids and endometrial polyps being common findings. The effectiveness of surgical removal to improve fertility remains uncertain. The associated surgical risks and costs highlight the need for more robust research in this area. The HELP Fertility? Study aimed to assess the clinical and cost-effectiveness of hysteroscopic removal of endometrial polyps and submucosal fibroids, compared to no removal, in improving fertility outcomes for participants with infertility or recurrent miscarriage while also evaluating participant experience and longer-term effects. The trial was designed as a multicentre, pragmatic superiority randomised controlled trial with two concurrent trials; one for endometrial polyps and one for submucosal fibroids, with a 9-month feasibility pilot. Participants were randomly assigned 1 : 1 to either receive hysteroscopic resection or no resection. The primary outcome was live birth rate at 15 months. Secondary outcomes included pregnancy rates, procedure details, patient satisfaction and resource use.</p><p><strong>Results: </strong>COVID-19 resulted in significant recruitment challenges, with delays in site set-up and participant enrolment due to pandemic-related healthcare disruptions. The trial was closed early by the National Institute for Health and Care Research-Health Technology Assessment programme following recruitment of 35 participants (19 hysteroscopic resection and 16 no resection) out of a target of 1120. The clinical and cost-effectiveness analyses were severely limited by the small sample size. Clinical pregnancy rates within 15 months of randomisation were 26.5% (5/19) in the hysteroscopic resection group and were 37.5% (6/16) in the no resection group. The live birth rate within 15 months of randomisation (the primary outcome) were 15.8% (3/19) in the hysteroscopic resection group and 18.8% (3/16) in the no resection group: a risk difference of -3.0% (95% confidence intervals -31.1% to 24.2%). No serious adverse events were observed in the follow-up. At the mean, hysteroscopic resection resulted in fewer live births, but increased costs, implying that resection is not cost-effective compared to no resection. However, results were highly uncertain and confidence intervals for incremental costs and the incremental live birth rate spanned zero. At a cost-effectiveness threshold of £20,000 per additional live birth, there is a 10% probability that hysteroscopic resection represents a cost-effective intervention and a 90% probability that no resection is cost-effective. There is a 56% probability that resection is more costly and less effective than no resection. Despite implementing remote training, centralised support and opening 16 National Health Service sites by February 2023, insufficient participants were recruited within planned time frames. The study was ultimately closed as part of the NIHR Research","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":" ","pages":"1-35"},"PeriodicalIF":4.0,"publicationDate":"2026-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12968972/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147344006","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}
Elizabeth Cook, Sophie James, Joanne Laycock, Ashley Scrimshire, Alex Mitchell, Heather Leggett, Alison Booth, Karen Glerum-Brooks, Catriona McDaid, Paul Baker, Maria Cann, Vicky Hanlon, Mike Reed, Martin Kiernan, Arabella Scantlebury, Luke Strachan, David Tate, David J Torgerson, Catherine E Hewitt
<p><strong>Background: </strong>The bacterium <i>Staphylococcus aureus</i> is a leading cause of hospital-acquired infections. These infections are difficult to treat when there is increasing resistance to penicillin, known as methicillin-resistant <i>Staphylococcus aureus</i>. Patients who carry <i>Staphylococcus aureus</i> in the nose and skin are prone to developing infections and many patients admitted to hospital are routinely 'decolonised' to reduce this risk. The current standard treatment for nasal decolonisation is the antibiotic nasal mupirocin. There are concerns about over-reliance on a single treatment and the risk of mupirocin-resistant methicillin-resistant <i>Staphylococcus aureus</i>. Robust evidence for alternatives to mupirocin is required.</p><p><strong>Objective: </strong>To investigate whether there are clinically and cost-effective alternatives to mupirocin for early nasal decolonisation of methicillin-resistant <i>Staphylococcus aureus</i> among adult hospital inpatients.</p><p><strong>Design and methods: </strong>We designed a multicentre, three-arm parallel-group, non-inferiority, randomised controlled trial with economic and qualitative evaluations, to recruit 3000 participants.</p><p><strong>Setting and participants: </strong>Adult hospital inpatients identified as being colonised with methicillin-resistant <i>Staphylococcus aureus</i> on routine hospital admission screening were eligible for inclusion.</p><p><strong>Interventions: </strong>Participants were randomised (ratio 1 : 1 : 1) to receive one of the following decolonisation treatments: mupirocin (2%) nasal ointment (3 g), polyhexanide (0.1%) nasal gel (30 ml) or chlorhexidine (0.1%) with neomycin (0.5%) nasal cream (15 g). Neither participants nor the investigators were blind to treatment allocation.</p><p><strong>Main outcome measures: </strong>The primary outcome was successful early nasal decolonisation, defined as a negative trial specific nasal methicillin-resistant <i>Staphylococcus aureus</i> swab taken 48 hours following treatment completion. Secondary outcomes included successful early nasal decolonisation of methicillin-resistant <i>Staphylococcus aureus</i> not fully susceptible to mupirocin, successful late nasal decolonisation, acceptability of treatment to patients, methicillin-resistant <i>Staphylococcus aureus</i> infections, length of hospital inpatient stays and re-admissions, adverse events and mortality. Outcomes were collected up to 4 weeks following treatment completion.</p><p><strong>Results: </strong>Recruitment and retention of participants were much lower than expected. In total, 297 patients were assessed for eligibility and 32 patients randomised. All participants received treatment as allocated. Seven participants withdrew from the study. The mean age was 73.8 years (standard deviation 16.6 years), with 62.5% (<i>n</i> = 20) of participants being male. Semistructured interviews were undertaken with patients (<i>N</i> = 5), clinical
{"title":"Effectiveness of polyhexanide, chlorhexidine with neomycin and mupirocin for nasal methicillin-resistant Staphylococcus aureus (MRSA) decolonisation: non-inferiority RCT (TIDE).","authors":"Elizabeth Cook, Sophie James, Joanne Laycock, Ashley Scrimshire, Alex Mitchell, Heather Leggett, Alison Booth, Karen Glerum-Brooks, Catriona McDaid, Paul Baker, Maria Cann, Vicky Hanlon, Mike Reed, Martin Kiernan, Arabella Scantlebury, Luke Strachan, David Tate, David J Torgerson, Catherine E Hewitt","doi":"10.3310/GJMR0715","DOIUrl":"10.3310/GJMR0715","url":null,"abstract":"<p><strong>Background: </strong>The bacterium <i>Staphylococcus aureus</i> is a leading cause of hospital-acquired infections. These infections are difficult to treat when there is increasing resistance to penicillin, known as methicillin-resistant <i>Staphylococcus aureus</i>. Patients who carry <i>Staphylococcus aureus</i> in the nose and skin are prone to developing infections and many patients admitted to hospital are routinely 'decolonised' to reduce this risk. The current standard treatment for nasal decolonisation is the antibiotic nasal mupirocin. There are concerns about over-reliance on a single treatment and the risk of mupirocin-resistant methicillin-resistant <i>Staphylococcus aureus</i>. Robust evidence for alternatives to mupirocin is required.</p><p><strong>Objective: </strong>To investigate whether there are clinically and cost-effective alternatives to mupirocin for early nasal decolonisation of methicillin-resistant <i>Staphylococcus aureus</i> among adult hospital inpatients.</p><p><strong>Design and methods: </strong>We designed a multicentre, three-arm parallel-group, non-inferiority, randomised controlled trial with economic and qualitative evaluations, to recruit 3000 participants.</p><p><strong>Setting and participants: </strong>Adult hospital inpatients identified as being colonised with methicillin-resistant <i>Staphylococcus aureus</i> on routine hospital admission screening were eligible for inclusion.</p><p><strong>Interventions: </strong>Participants were randomised (ratio 1 : 1 : 1) to receive one of the following decolonisation treatments: mupirocin (2%) nasal ointment (3 g), polyhexanide (0.1%) nasal gel (30 ml) or chlorhexidine (0.1%) with neomycin (0.5%) nasal cream (15 g). Neither participants nor the investigators were blind to treatment allocation.</p><p><strong>Main outcome measures: </strong>The primary outcome was successful early nasal decolonisation, defined as a negative trial specific nasal methicillin-resistant <i>Staphylococcus aureus</i> swab taken 48 hours following treatment completion. Secondary outcomes included successful early nasal decolonisation of methicillin-resistant <i>Staphylococcus aureus</i> not fully susceptible to mupirocin, successful late nasal decolonisation, acceptability of treatment to patients, methicillin-resistant <i>Staphylococcus aureus</i> infections, length of hospital inpatient stays and re-admissions, adverse events and mortality. Outcomes were collected up to 4 weeks following treatment completion.</p><p><strong>Results: </strong>Recruitment and retention of participants were much lower than expected. In total, 297 patients were assessed for eligibility and 32 patients randomised. All participants received treatment as allocated. Seven participants withdrew from the study. The mean age was 73.8 years (standard deviation 16.6 years), with 62.5% (<i>n</i> = 20) of participants being male. Semistructured interviews were undertaken with patients (<i>N</i> = 5), clinical","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":" ","pages":"1-34"},"PeriodicalIF":4.0,"publicationDate":"2026-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12968953/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147344009","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}
Elizabeth Lumley, Alicia O'Cathain, Katie Ridsdale, Sarah Drabble, David White, Clare Pye, Jessica Wright, Andrew Drakeley, Ying Cheong, Raj Mathur, Amy Barr, Mostafa Metwally
Background: Ovarian hyperstimulation syndrome is a significant complication of fertility treatment, where the ovaries become enlarged if they are overstimulated, resulting in fluid leakage. Ovarian hyperstimulation syndrome can be classified as mild, moderate or severe. Symptoms vary dependent on severity but can include abdominal swelling, pain, nausea and vomiting, and shortness of breath. Treatment typically consists of monitoring initially, with active intervention if the condition progresses to a severe state, requiring hospitalisation. This study explored the acceptability and feasibility of outpatient paracentesis, and of gonadotropin-releasing hormone antagonists, as early interventions for ovarian hyperstimulation syndrome.
Methods: We conducted qualitative semi-structured interviews with healthcare professionals from fertility clinics (n = 8) and patients who had experienced ovarian hyperstimulation syndrome (n = 10) across six United Kingdom fertility clinics. Interviews explored views on the proposed treatment protocols, and potential barriers and facilitators to randomised controlled trials evaluating these treatments.
Results: Both healthcare professionals and patients were supportive of the proposed trials. Key findings included that healthcare professionals recommended clarity on patient eligibility, hospitalisation criteria and consent procedures. Patients expressed a desire to be given more detailed information about potential trials and had mixed opinions on self-monitoring. There were some concerns from both parties about treatment risks, particularly the paracentesis. Healthcare professionals noted a shift to more preventative practice due to the COVID-19 pandemic.
Conclusions: Outpatient paracentesis and gonadotropin-releasing hormone antagonists were perceived as promising interventions. Potential concerns and recommendations around both acceptability and feasibility were raised, which were used to refine the treatment protocols for the Shaping and Trialling Outpatient Protocols for Ovarian Hyperstimulation Syndrome trial.
Funding: This article presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number NIHR128137.
{"title":"Views on outpatient paracentesis and GnRH antagonists for ovarian hyperstimulation syndrome: a qualitative study of patients and healthcare professionals.","authors":"Elizabeth Lumley, Alicia O'Cathain, Katie Ridsdale, Sarah Drabble, David White, Clare Pye, Jessica Wright, Andrew Drakeley, Ying Cheong, Raj Mathur, Amy Barr, Mostafa Metwally","doi":"10.3310/GJMM2923","DOIUrl":"10.3310/GJMM2923","url":null,"abstract":"<p><strong>Background: </strong>Ovarian hyperstimulation syndrome is a significant complication of fertility treatment, where the ovaries become enlarged if they are overstimulated, resulting in fluid leakage. Ovarian hyperstimulation syndrome can be classified as mild, moderate or severe. Symptoms vary dependent on severity but can include abdominal swelling, pain, nausea and vomiting, and shortness of breath. Treatment typically consists of monitoring initially, with active intervention if the condition progresses to a severe state, requiring hospitalisation. This study explored the acceptability and feasibility of outpatient paracentesis, and of gonadotropin-releasing hormone antagonists, as early interventions for ovarian hyperstimulation syndrome.</p><p><strong>Methods: </strong>We conducted qualitative semi-structured interviews with healthcare professionals from fertility clinics (<i>n</i> = 8) and patients who had experienced ovarian hyperstimulation syndrome (<i>n</i> = 10) across six United Kingdom fertility clinics. Interviews explored views on the proposed treatment protocols, and potential barriers and facilitators to randomised controlled trials evaluating these treatments.</p><p><strong>Results: </strong>Both healthcare professionals and patients were supportive of the proposed trials. Key findings included that healthcare professionals recommended clarity on patient eligibility, hospitalisation criteria and consent procedures. Patients expressed a desire to be given more detailed information about potential trials and had mixed opinions on self-monitoring. There were some concerns from both parties about treatment risks, particularly the paracentesis. Healthcare professionals noted a shift to more preventative practice due to the COVID-19 pandemic.</p><p><strong>Conclusions: </strong>Outpatient paracentesis and gonadotropin-releasing hormone antagonists were perceived as promising interventions. Potential concerns and recommendations around both acceptability and feasibility were raised, which were used to refine the treatment protocols for the Shaping and Trialling Outpatient Protocols for Ovarian Hyperstimulation Syndrome trial.</p><p><strong>Funding: </strong>This article presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number NIHR128137.</p>","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":" ","pages":"1-14"},"PeriodicalIF":4.0,"publicationDate":"2026-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12968949/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147343987","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}
Mark Corbett, Chinyereugo Umemneku-Chikere, Sarah Nevitt, Nyanar Jasmine Deng, Matthew Walton, Helen Fulbright, Chong Yew Tan, Robin Lachmann, Rachel Churchill, Robert Hodgson
<p><strong>Background: </strong>Late-onset Pompe disease is a rare inherited genetic condition that causes progressive muscle dysfunction and damage. As the disease advances, the progressive weakening of respiratory muscles significantly increases the risk of respiratory failure, which is a major contributor to premature mortality. Enzyme replacement therapy is the primary treatment for Pompe disease.</p><p><strong>Objective: </strong>To investigate the clinical impact of enzyme replacement therapies for the treatment and management of late-onset Pompe disease and establish the relative effectiveness of enzyme replacement therapy compared to best supportive care (in the absence of enzyme replacement therapy).</p><p><strong>Methods: </strong>A systematic review and network meta-analysis of published evidence on the clinical effectiveness of enzyme replacement therapy and best supportive care was undertaken. Comprehensive bibliographic database searches were conducted up to May 2024 to identify randomised controlled trials or any other prospective enzyme replacement therapy studies in patients with Pompe disease. Network meta-analyses of randomised controlled trials were undertaken to estimate indirect treatment effects for forced vital capacity % predicted and the 6-minute walk test. Other studies were summarised using narrative synthesis.</p><p><strong>Results: </strong>The review included 60 studies: 38 on enzyme replacement therapy and 22 on best supportive care. Enzyme replacement therapy studies comprised 3 randomised controlled trials, 3 randomised controlled trial extensions, 7 registry studies and 25 single-group prospective studies. Two randomised controlled trials had a high risk of bias. Best supportive care studies included 14 longitudinal and 8 cross-sectional studies. In the network meta-analyses, after approximately 1 year, enzyme replacement therapy-naive patients showed significant 6-minute walk test improvements versus placebo: ~25 m with alglucosidase alfa and ~54 m with avalglucosidase alfa. No significant differences were found for forced vital capacity % predicted or comparisons with cipaglucosidase alfa, although very few enzyme replacement therapy-naive patients taking cipaglucosidase alfa were available for inclusion in the analyses. Intra-enzyme replacement therapy comparisons showed a significant 6-minute walk test advantage for avalglucosidase alfa. However, a sensitivity analysis adjusting for skewed data revealed no significant differences. Long-term enzyme replacement therapy effectiveness was assessed in single-group studies, showing initial gains maintained for 1-3 years, followed by gradual 10- to 15-year declines in 6-minute walk test and forced vital capacity % predicted. However, small sample sizes and missing data introduce uncertainty. Long-term evidence on best supportive care is limited, with most of the evidence focused on characterising basic demographic information and support needs. A small number of st
{"title":"Enzyme replacement therapy compared with best supportive care for the treatment of Pompe Disease: a systematic review and network meta-analysis.","authors":"Mark Corbett, Chinyereugo Umemneku-Chikere, Sarah Nevitt, Nyanar Jasmine Deng, Matthew Walton, Helen Fulbright, Chong Yew Tan, Robin Lachmann, Rachel Churchill, Robert Hodgson","doi":"10.3310/GJRH0730","DOIUrl":"10.3310/GJRH0730","url":null,"abstract":"<p><strong>Background: </strong>Late-onset Pompe disease is a rare inherited genetic condition that causes progressive muscle dysfunction and damage. As the disease advances, the progressive weakening of respiratory muscles significantly increases the risk of respiratory failure, which is a major contributor to premature mortality. Enzyme replacement therapy is the primary treatment for Pompe disease.</p><p><strong>Objective: </strong>To investigate the clinical impact of enzyme replacement therapies for the treatment and management of late-onset Pompe disease and establish the relative effectiveness of enzyme replacement therapy compared to best supportive care (in the absence of enzyme replacement therapy).</p><p><strong>Methods: </strong>A systematic review and network meta-analysis of published evidence on the clinical effectiveness of enzyme replacement therapy and best supportive care was undertaken. Comprehensive bibliographic database searches were conducted up to May 2024 to identify randomised controlled trials or any other prospective enzyme replacement therapy studies in patients with Pompe disease. Network meta-analyses of randomised controlled trials were undertaken to estimate indirect treatment effects for forced vital capacity % predicted and the 6-minute walk test. Other studies were summarised using narrative synthesis.</p><p><strong>Results: </strong>The review included 60 studies: 38 on enzyme replacement therapy and 22 on best supportive care. Enzyme replacement therapy studies comprised 3 randomised controlled trials, 3 randomised controlled trial extensions, 7 registry studies and 25 single-group prospective studies. Two randomised controlled trials had a high risk of bias. Best supportive care studies included 14 longitudinal and 8 cross-sectional studies. In the network meta-analyses, after approximately 1 year, enzyme replacement therapy-naive patients showed significant 6-minute walk test improvements versus placebo: ~25 m with alglucosidase alfa and ~54 m with avalglucosidase alfa. No significant differences were found for forced vital capacity % predicted or comparisons with cipaglucosidase alfa, although very few enzyme replacement therapy-naive patients taking cipaglucosidase alfa were available for inclusion in the analyses. Intra-enzyme replacement therapy comparisons showed a significant 6-minute walk test advantage for avalglucosidase alfa. However, a sensitivity analysis adjusting for skewed data revealed no significant differences. Long-term enzyme replacement therapy effectiveness was assessed in single-group studies, showing initial gains maintained for 1-3 years, followed by gradual 10- to 15-year declines in 6-minute walk test and forced vital capacity % predicted. However, small sample sizes and missing data introduce uncertainty. Long-term evidence on best supportive care is limited, with most of the evidence focused on characterising basic demographic information and support needs. A small number of st","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":" ","pages":"1-58"},"PeriodicalIF":4.0,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12926851/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146201492","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}
Nina Wilson, Miranda Morton, Tara Homer, Ann Breeze Konkoth, Richard Joyce, Anneka Kershaw, Hazel Wilde, Alison Liddle, James Wason, Laura Ternent, Maria Allen, Robert Lord, John Steer, Graham Devereux, James D Chalmers, Adam T Hill, Charles S Haworth, John R Hurst, And Anthony De Soyza
<p><strong>Background: </strong>Bronchiectasis is a long-term lung condition associated with bronchial dilatation, chronic inflammation and infection. Treatment is often empirical or extrapolated from other lung conditions, for example the use of inhaled therapies licensed for use in asthma or chronic obstructive pulmonary disease. Inhaled therapies, such as corticosteroids or long-acting bronchodilators (long-acting beta agonists or long-acting muscarinic antagonists), are commonly used in bronchiectasis despite scanty evidence on exacerbation reduction.</p><p><strong>Objective: </strong>To assess whether: dual bronchodilators (long-acting beta agonists/long-acting muscarinic antagonists) either as stand-alone therapy or in combination with inhaled corticosteroid are superior to placebo at reducing mean exacerbation rates over 12 months dual bronchodilators (long-acting beta agonists/long-acting muscarinic antagonists) are non-inferior to triple therapy (inhaled corticosteroid/long-acting beta agonists/long-acting muscarinic antagonists) at reducing mean exacerbation rates over 12 months.</p><p><strong>Design: </strong>Pragmatic, multicentre, placebo-controlled, three-arm, double-blinded, prospective, randomised controlled trial incorporating a 12-month internal pilot.</p><p><strong>Target population: </strong>Six hundred adults with bronchiectasis and history of ≥ 2 exacerbations in any 12-month period within the preceding 2 years.</p><p><strong>Setting: </strong>United Kingdom National Health Service secondary care sites.</p><p><strong>Interventions: </strong>Twelve months, one puff daily of either dual therapy [55 μg umeclidinium (long-acting muscarinic antagonists) and 22 μg vilanterol (long-acting beta agonists)], triple therapy [dual therapy plus 92 μg fluticasone furoate (inhaled corticosteroid)] or matched placebo dry powder inhalers, randomised in a 2 : 2 : 1 ratio, respectively.</p><p><strong>Outcome measures: </strong>Primary: number of participants reported bronchiectasis exacerbations requiring treatment with antibiotics during the 12-month treatment period. Primary economic: incremental cost per quality-adjusted life-year gained at 12 months.</p><p><strong>Results: </strong>Recruitment rates did not follow projections due to the COVID-19 pandemic; 85 potentially eligible patients were screened, of whom 33 (39%) were randomised. Of the randomised participants, 30 (91%) completed follow-up at 12 months; 3 participants withdrew [1/14 (7%) dual therapy, 1/12 (8%) triple therapy and 1/7 (14%) placebo]. Five participants discontinued therapy during the trial [1/14 (7%) dual therapy, 2/12 (17%) triple therapy and 2/7 (29%) placebo]. Given the small sample size, the statistical and economic analyses are descriptive and exploratory. Exacerbation data were available for 32/33 (97%) of randomised participants (13 dual therapy, 12 triple therapy and 7 placebo). The median number of exacerbations during the follow-up (the primary outcome) was 1
{"title":"A pragmatic, multicentre, placebo-controlled, 3-arm, double-blinded, randomised controlled trial, incorporating an internal pilot, to determine the role of bronchodilators in preventing exacerbations of bronchiectasis.","authors":"Nina Wilson, Miranda Morton, Tara Homer, Ann Breeze Konkoth, Richard Joyce, Anneka Kershaw, Hazel Wilde, Alison Liddle, James Wason, Laura Ternent, Maria Allen, Robert Lord, John Steer, Graham Devereux, James D Chalmers, Adam T Hill, Charles S Haworth, John R Hurst, And Anthony De Soyza","doi":"10.3310/GGCC1111","DOIUrl":"https://doi.org/10.3310/GGCC1111","url":null,"abstract":"<p><strong>Background: </strong>Bronchiectasis is a long-term lung condition associated with bronchial dilatation, chronic inflammation and infection. Treatment is often empirical or extrapolated from other lung conditions, for example the use of inhaled therapies licensed for use in asthma or chronic obstructive pulmonary disease. Inhaled therapies, such as corticosteroids or long-acting bronchodilators (long-acting beta agonists or long-acting muscarinic antagonists), are commonly used in bronchiectasis despite scanty evidence on exacerbation reduction.</p><p><strong>Objective: </strong>To assess whether: dual bronchodilators (long-acting beta agonists/long-acting muscarinic antagonists) either as stand-alone therapy or in combination with inhaled corticosteroid are superior to placebo at reducing mean exacerbation rates over 12 months dual bronchodilators (long-acting beta agonists/long-acting muscarinic antagonists) are non-inferior to triple therapy (inhaled corticosteroid/long-acting beta agonists/long-acting muscarinic antagonists) at reducing mean exacerbation rates over 12 months.</p><p><strong>Design: </strong>Pragmatic, multicentre, placebo-controlled, three-arm, double-blinded, prospective, randomised controlled trial incorporating a 12-month internal pilot.</p><p><strong>Target population: </strong>Six hundred adults with bronchiectasis and history of ≥ 2 exacerbations in any 12-month period within the preceding 2 years.</p><p><strong>Setting: </strong>United Kingdom National Health Service secondary care sites.</p><p><strong>Interventions: </strong>Twelve months, one puff daily of either dual therapy [55 μg umeclidinium (long-acting muscarinic antagonists) and 22 μg vilanterol (long-acting beta agonists)], triple therapy [dual therapy plus 92 μg fluticasone furoate (inhaled corticosteroid)] or matched placebo dry powder inhalers, randomised in a 2 : 2 : 1 ratio, respectively.</p><p><strong>Outcome measures: </strong>Primary: number of participants reported bronchiectasis exacerbations requiring treatment with antibiotics during the 12-month treatment period. Primary economic: incremental cost per quality-adjusted life-year gained at 12 months.</p><p><strong>Results: </strong>Recruitment rates did not follow projections due to the COVID-19 pandemic; 85 potentially eligible patients were screened, of whom 33 (39%) were randomised. Of the randomised participants, 30 (91%) completed follow-up at 12 months; 3 participants withdrew [1/14 (7%) dual therapy, 1/12 (8%) triple therapy and 1/7 (14%) placebo]. Five participants discontinued therapy during the trial [1/14 (7%) dual therapy, 2/12 (17%) triple therapy and 2/7 (29%) placebo]. Given the small sample size, the statistical and economic analyses are descriptive and exploratory. Exacerbation data were available for 32/33 (97%) of randomised participants (13 dual therapy, 12 triple therapy and 7 placebo). The median number of exacerbations during the follow-up (the primary outcome) was 1","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":" ","pages":"1-77"},"PeriodicalIF":4.0,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146142375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
John Lowe, David Gillespie, Ali Aboklaish, Tin Man Mandy Lau, Claudia Consoli, Malavika Babu, Mark Goddard, Kerenza Hood, Nigel Klein, Emma Thomas-Jones, Sinead Ahearn-Ford, Greg Young, Christopher Stewart, Mark Turner, Marie Hubbard, Julian Marchesi, Janet Berrington, Sailesh Kotecha
<p><strong>Background: </strong>Systematic reviews have reported conflicting evidence to confirm if macrolides reduce rates of chronic lung disease of prematurity in at-risk preterm-born infants, including in those colonised with pulmonary <i>Ureaplasma</i> spp. Since an adequately powered trial has been lacking, we conducted a double-blind, randomised, placebo-controlled trial to assess if the macrolide azithromycin improved survival without the development of physiologically defined moderate or severe chronic lung disease of prematurity in infants born at < 30 weeks' gestation.</p><p><strong>Methods: </strong>Infants recruited from 30 neonatal units (median gestational age 27.0 weeks, interquartile range 25.3-28.6) requiring respiratory support within 72 hours of birth were randomised to intravenous azithromycin 20 mg/kg/day for 3 days followed by 10 mg/kg for 7 days or to placebo. Primary outcome was survival without development of physiologically defined moderate/severe chronic lung disease of prematurity at 36 weeks' postmenstrual age. A total of 796 infants were required to detect 12% improvement in survival without development of moderate or severe chronic lung disease of prematurity, including 10% dropout, with two-sided <i>α</i>-level of 5% and 90% power. The primary outcome was analysed using three-level logistic regression to account for clustering of multiple births and participants within centres and was adjusted for gestational age as a fixed effect. Secondary outcomes included death, chronic lung disease of prematurity severity, treatment interaction with <i>Ureaplasma</i> spp. colonisation, days of invasive and days of non-invasive respiratory support, treatment for nosocomial infections, treated patent ductus arteriosus, severe intraventricular haemorrhage, necrotising enterocolitis, treated retinopathy of prematurity and emergence of azithromycin resistance in stool and respiratory samples. Quantitative polymerase chain reaction identified respiratory <i>Ureaplasma</i> spp. and antibiotic resistance genes. Safety was also monitored.</p><p><strong>Findings: </strong>After three withdrawals, 796 randomised infants were included in the final analyses. Survivors without physiologically defined moderate/severe chronic lung disease of prematurity were: 166/394 (42.1%) and 179/402 (44.5%) in the intervention and placebo groups, respectively (adjusted odds ratio 0.84; 95% confidence interval 0.55 to 1.29; <i>p</i> = 0.43). Secondary outcomes were not significantly different between the treatment groups, except for treated retinopathy of prematurity in survivors (3.5% vs. 7.4%, azithromycin vs. placebo; odds ratio: 0.42, 95% confidence interval 0.18 to 0.98). <i>Ureaplasma</i> spp. colonisation did not influence treatment effect. No significant serious adverse effects were reported. From 1108 (<i>n</i> = 541 azithromycin, <i>n</i> = 567 placebo) respiratory aspirates and 709 stool samples from 348 infants, <i>erm</i>(C) and <i>msr</i>(A)
{"title":"Azithromycin therapy for prevention of chronic lung disease of prematurity (AZTEC): a randomised placebo-controlled trial.","authors":"John Lowe, David Gillespie, Ali Aboklaish, Tin Man Mandy Lau, Claudia Consoli, Malavika Babu, Mark Goddard, Kerenza Hood, Nigel Klein, Emma Thomas-Jones, Sinead Ahearn-Ford, Greg Young, Christopher Stewart, Mark Turner, Marie Hubbard, Julian Marchesi, Janet Berrington, Sailesh Kotecha","doi":"10.3310/GJSK0401","DOIUrl":"10.3310/GJSK0401","url":null,"abstract":"<p><strong>Background: </strong>Systematic reviews have reported conflicting evidence to confirm if macrolides reduce rates of chronic lung disease of prematurity in at-risk preterm-born infants, including in those colonised with pulmonary <i>Ureaplasma</i> spp. Since an adequately powered trial has been lacking, we conducted a double-blind, randomised, placebo-controlled trial to assess if the macrolide azithromycin improved survival without the development of physiologically defined moderate or severe chronic lung disease of prematurity in infants born at < 30 weeks' gestation.</p><p><strong>Methods: </strong>Infants recruited from 30 neonatal units (median gestational age 27.0 weeks, interquartile range 25.3-28.6) requiring respiratory support within 72 hours of birth were randomised to intravenous azithromycin 20 mg/kg/day for 3 days followed by 10 mg/kg for 7 days or to placebo. Primary outcome was survival without development of physiologically defined moderate/severe chronic lung disease of prematurity at 36 weeks' postmenstrual age. A total of 796 infants were required to detect 12% improvement in survival without development of moderate or severe chronic lung disease of prematurity, including 10% dropout, with two-sided <i>α</i>-level of 5% and 90% power. The primary outcome was analysed using three-level logistic regression to account for clustering of multiple births and participants within centres and was adjusted for gestational age as a fixed effect. Secondary outcomes included death, chronic lung disease of prematurity severity, treatment interaction with <i>Ureaplasma</i> spp. colonisation, days of invasive and days of non-invasive respiratory support, treatment for nosocomial infections, treated patent ductus arteriosus, severe intraventricular haemorrhage, necrotising enterocolitis, treated retinopathy of prematurity and emergence of azithromycin resistance in stool and respiratory samples. Quantitative polymerase chain reaction identified respiratory <i>Ureaplasma</i> spp. and antibiotic resistance genes. Safety was also monitored.</p><p><strong>Findings: </strong>After three withdrawals, 796 randomised infants were included in the final analyses. Survivors without physiologically defined moderate/severe chronic lung disease of prematurity were: 166/394 (42.1%) and 179/402 (44.5%) in the intervention and placebo groups, respectively (adjusted odds ratio 0.84; 95% confidence interval 0.55 to 1.29; <i>p</i> = 0.43). Secondary outcomes were not significantly different between the treatment groups, except for treated retinopathy of prematurity in survivors (3.5% vs. 7.4%, azithromycin vs. placebo; odds ratio: 0.42, 95% confidence interval 0.18 to 0.98). <i>Ureaplasma</i> spp. colonisation did not influence treatment effect. No significant serious adverse effects were reported. From 1108 (<i>n</i> = 541 azithromycin, <i>n</i> = 567 placebo) respiratory aspirates and 709 stool samples from 348 infants, <i>erm</i>(C) and <i>msr</i>(A)","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":"30 12","pages":"1-17"},"PeriodicalIF":4.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12914749/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146142412","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}
Penny Rapaport, Sarah Amador, Mariam Adeleke, Julie Barber, Sube Banerjee, Ankita Bhojwani, Georgina Charlesworth, Chris Clarke, Colin Espie, Lina Gonzalez, Rossana Horsley, Rachael Hunter, Simon Kyle, Monica Manela, Naaheed Mukadam, Malvika Muralidhar, Malgorzata Raczek, Zuzana Walker, Lucy Webster, Hang Yuan, Gill Livingston
<p><strong>Background: </strong>Sleep disturbances are common and distressing for people with dementia and their family carers and can lead to carers having interrupted sleep, low mood and care breakdown. Medication can have harmful side effects and is generally ineffective. Non-pharmacological interventions should be first-line treatments, yet until now there have not been effective treatments.</p><p><strong>Objectives: </strong>To establish whether Dementia RElAted Manual for Sleep; STrAtegies for RelaTives (DREAMS START), a multicomponent intervention, reduced sleep disturbance in people with dementia living at home at 8 months compared with National Health Service treatment (treatment as usual).</p><p><strong>Design and methods: </strong>We conducted a two-arm, multicentre, parallel-arm, superiority randomised controlled trial with masked outcome assessment. Participants were randomised (1 : 1 ratio) to DREAMS START intervention plus treatment as usual or treatment as usual alone. Analyses were intention to treat. We conducted a mixed-method process evaluation with additional substudies: one exploring how United Kingdom-based South Asians experience sleep disturbance and dementia, and one exploring the interaction of sleep, dementia and long-term conditions.</p><p><strong>Settings and participants: </strong>We recruited dyads of people with dementia and sleep disturbance living at home and family carers from 12 National Health Service trusts and the Join Dementia Research service in England.</p><p><strong>Interventions: </strong>DREAMS START is a six-session, multicomponent, manualised intervention delivered to family carers of people with dementia who implement strategies to improve their relatives' sleep. It is delivered face to face or remotely by non-clinically trained graduates weekly or fortnightly and incorporates information about sleep and dementia, promotes de-arousal at night, adaptive stimulus control (e.g. bedtime routine maintenance), daytime behavioural activation, increasing access to light, improving carer sleep and making a tailored action plan.</p><p><strong>Main outcome measures: </strong>The primary outcome was sleep disturbance measured using the Sleep Disorders Inventory at 8 months.</p><p><strong>Results: </strong>Between February 2021 and March 2023, 377 dyads were randomly assigned, 189 to treatment as usual and 188 to DREAMS START plus treatment as usual. Mean age of participants with dementia was 79.4 years (standard deviation 9.0), and 206 (55%) were women. Mean Sleep Disorders Inventory score at 8 months was lower in the intervention versus treatment-as-usual arm [15.16 (standard deviation 12.77), <i>n</i> = 159, vs. 20.34 (16.67), <i>n</i> = 163]; adjusted difference in means [-4.70 (95% confidence interval -7.65 to -1.74); <i>p</i> = 0.002]. Seventeen (9%) people with dementia in the intervention and 17 (9%) in the control arm died during the trial; deaths were unrelated to the intervention. The mean incrementa
{"title":"The clinical and cost-effectiveness of improving sleep via carer delivered strategies in people with dementia: the DREAMS START parallel multi-centre RCT.","authors":"Penny Rapaport, Sarah Amador, Mariam Adeleke, Julie Barber, Sube Banerjee, Ankita Bhojwani, Georgina Charlesworth, Chris Clarke, Colin Espie, Lina Gonzalez, Rossana Horsley, Rachael Hunter, Simon Kyle, Monica Manela, Naaheed Mukadam, Malvika Muralidhar, Malgorzata Raczek, Zuzana Walker, Lucy Webster, Hang Yuan, Gill Livingston","doi":"10.3310/GJPR2620","DOIUrl":"10.3310/GJPR2620","url":null,"abstract":"<p><strong>Background: </strong>Sleep disturbances are common and distressing for people with dementia and their family carers and can lead to carers having interrupted sleep, low mood and care breakdown. Medication can have harmful side effects and is generally ineffective. Non-pharmacological interventions should be first-line treatments, yet until now there have not been effective treatments.</p><p><strong>Objectives: </strong>To establish whether Dementia RElAted Manual for Sleep; STrAtegies for RelaTives (DREAMS START), a multicomponent intervention, reduced sleep disturbance in people with dementia living at home at 8 months compared with National Health Service treatment (treatment as usual).</p><p><strong>Design and methods: </strong>We conducted a two-arm, multicentre, parallel-arm, superiority randomised controlled trial with masked outcome assessment. Participants were randomised (1 : 1 ratio) to DREAMS START intervention plus treatment as usual or treatment as usual alone. Analyses were intention to treat. We conducted a mixed-method process evaluation with additional substudies: one exploring how United Kingdom-based South Asians experience sleep disturbance and dementia, and one exploring the interaction of sleep, dementia and long-term conditions.</p><p><strong>Settings and participants: </strong>We recruited dyads of people with dementia and sleep disturbance living at home and family carers from 12 National Health Service trusts and the Join Dementia Research service in England.</p><p><strong>Interventions: </strong>DREAMS START is a six-session, multicomponent, manualised intervention delivered to family carers of people with dementia who implement strategies to improve their relatives' sleep. It is delivered face to face or remotely by non-clinically trained graduates weekly or fortnightly and incorporates information about sleep and dementia, promotes de-arousal at night, adaptive stimulus control (e.g. bedtime routine maintenance), daytime behavioural activation, increasing access to light, improving carer sleep and making a tailored action plan.</p><p><strong>Main outcome measures: </strong>The primary outcome was sleep disturbance measured using the Sleep Disorders Inventory at 8 months.</p><p><strong>Results: </strong>Between February 2021 and March 2023, 377 dyads were randomly assigned, 189 to treatment as usual and 188 to DREAMS START plus treatment as usual. Mean age of participants with dementia was 79.4 years (standard deviation 9.0), and 206 (55%) were women. Mean Sleep Disorders Inventory score at 8 months was lower in the intervention versus treatment-as-usual arm [15.16 (standard deviation 12.77), <i>n</i> = 159, vs. 20.34 (16.67), <i>n</i> = 163]; adjusted difference in means [-4.70 (95% confidence interval -7.65 to -1.74); <i>p</i> = 0.002]. Seventeen (9%) people with dementia in the intervention and 17 (9%) in the control arm died during the trial; deaths were unrelated to the intervention. The mean incrementa","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":"30 17","pages":"1-26"},"PeriodicalIF":4.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12907995/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146149594","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}
Doug Gould, Samiran Ray, Irene Chang, Elisa Giallongo, Marzena Orzol, Lauran O'Neill, Rachel Agbeko, Carly Au, Elizabeth Draper, Lee Elliot-Major, Gareth Jones, Lamprini Lampro, Jon Lillie, John Pappachan, Samiran Peters, Padmanabhan Ramnarayan, Zia Sadique, Karen Thomas, Silvia Moler-Zapata, Kathryn Rowan, David Harrison, Paul Mouncey, Mark Peters
<p><strong>Background: </strong>The optimal target for systemic oxygenation in critically ill children is unknown. Liberal oxygenation is widely practised but is associated with harm in observational studies.</p><p><strong>Objectives: </strong>To evaluate the clinical and cost-effectiveness of a conservative oxygenation target of peripheral oxygen saturation 88-92% compared with peripheral oxygen saturation > 94% in critically ill children admitted to paediatric intensive care unit as an emergency.</p><p><strong>Design and setting: </strong>A pragmatic, open, multicentre, parallel-group, randomised clinical trial conducted in 15 National Health Service paediatric intensive care units and associated emergency transport services across England and Scotland.</p><p><strong>Participants: </strong>Children aged > 38 weeks corrected gestational age and < 16 years, enrolled within 6 hours of being accepted for admission to paediatric intensive care unit as an emergency; receiving invasive mechanical ventilation with supplemental oxygen; and in face-to-face contact with paediatric intensive care unit or emergency transport services staff.</p><p><strong>Interventions: </strong>Adjustment of ventilator and inspired oxygen settings aiming to achieve peripheral oxygen saturation 88-92% (conservative oxygenation) or peripheral oxygen saturation > 94% (liberal oxygenation) during invasive mechanical ventilation.</p><p><strong>Main outcome measures: </strong>Primary outcomes: duration of organ support at 30 days, with death by day 30 ranked as the worst outcome (clinical effectiveness) and incremental costs, quality-adjusted life-years and net monetary benefit at 12 months (cost-effectiveness). Secondary outcomes: incremental costs at 30 days; mortality at paediatric intensive care unit discharge, 30 days, 90 days and 12 months; time to liberation from ventilation; duration of organ support; length of paediatric intensive care unit and hospital stay; functional status at paediatric intensive care unit discharge; and health-related quality of life at 12 months.</p><p><strong>Results: </strong>Two thousand and forty children were randomised between 1 September 2020 and 15 May 2022. Consent was obtained for 1872 (94%) - 939 to the conservative and 933 to the liberal oxygenation group - who were included in the primary analysis. Duration of organ support or death in the first 30 days was lower in the conservative oxygenation group [probabilistic index 0.53, 95% confidence interval 0.50 to 0.55; <i>p</i> = 0.04 Wilcoxon rank-sum test, adjusted odds ratio 0.84 (95% confidence interval 0.72 to 0.99)]. Both components of the composite primary outcome and secondary outcomes favoured conservative oxygenation. Average costs at 30 days strongly indicated lower costs with conservative oxygenation. Longer-term estimated incremental costs and quality-adjusted life-years were lower and net monetary benefit marginally favoured conservative oxygenation but with wide uncertainty [
{"title":"Conservative versus liberal oxygenation targets in critically ill children: the Oxy-PICU RCT.","authors":"Doug Gould, Samiran Ray, Irene Chang, Elisa Giallongo, Marzena Orzol, Lauran O'Neill, Rachel Agbeko, Carly Au, Elizabeth Draper, Lee Elliot-Major, Gareth Jones, Lamprini Lampro, Jon Lillie, John Pappachan, Samiran Peters, Padmanabhan Ramnarayan, Zia Sadique, Karen Thomas, Silvia Moler-Zapata, Kathryn Rowan, David Harrison, Paul Mouncey, Mark Peters","doi":"10.3310/HHYY5898","DOIUrl":"10.3310/HHYY5898","url":null,"abstract":"<p><strong>Background: </strong>The optimal target for systemic oxygenation in critically ill children is unknown. Liberal oxygenation is widely practised but is associated with harm in observational studies.</p><p><strong>Objectives: </strong>To evaluate the clinical and cost-effectiveness of a conservative oxygenation target of peripheral oxygen saturation 88-92% compared with peripheral oxygen saturation > 94% in critically ill children admitted to paediatric intensive care unit as an emergency.</p><p><strong>Design and setting: </strong>A pragmatic, open, multicentre, parallel-group, randomised clinical trial conducted in 15 National Health Service paediatric intensive care units and associated emergency transport services across England and Scotland.</p><p><strong>Participants: </strong>Children aged > 38 weeks corrected gestational age and < 16 years, enrolled within 6 hours of being accepted for admission to paediatric intensive care unit as an emergency; receiving invasive mechanical ventilation with supplemental oxygen; and in face-to-face contact with paediatric intensive care unit or emergency transport services staff.</p><p><strong>Interventions: </strong>Adjustment of ventilator and inspired oxygen settings aiming to achieve peripheral oxygen saturation 88-92% (conservative oxygenation) or peripheral oxygen saturation > 94% (liberal oxygenation) during invasive mechanical ventilation.</p><p><strong>Main outcome measures: </strong>Primary outcomes: duration of organ support at 30 days, with death by day 30 ranked as the worst outcome (clinical effectiveness) and incremental costs, quality-adjusted life-years and net monetary benefit at 12 months (cost-effectiveness). Secondary outcomes: incremental costs at 30 days; mortality at paediatric intensive care unit discharge, 30 days, 90 days and 12 months; time to liberation from ventilation; duration of organ support; length of paediatric intensive care unit and hospital stay; functional status at paediatric intensive care unit discharge; and health-related quality of life at 12 months.</p><p><strong>Results: </strong>Two thousand and forty children were randomised between 1 September 2020 and 15 May 2022. Consent was obtained for 1872 (94%) - 939 to the conservative and 933 to the liberal oxygenation group - who were included in the primary analysis. Duration of organ support or death in the first 30 days was lower in the conservative oxygenation group [probabilistic index 0.53, 95% confidence interval 0.50 to 0.55; <i>p</i> = 0.04 Wilcoxon rank-sum test, adjusted odds ratio 0.84 (95% confidence interval 0.72 to 0.99)]. Both components of the composite primary outcome and secondary outcomes favoured conservative oxygenation. Average costs at 30 days strongly indicated lower costs with conservative oxygenation. Longer-term estimated incremental costs and quality-adjusted life-years were lower and net monetary benefit marginally favoured conservative oxygenation but with wide uncertainty [","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":"30 13","pages":"1-20"},"PeriodicalIF":4.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12907991/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146149670","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}
Samir Gupta, Nimish V Subhedar, Jennifer L Bell, Ursula Bowler, Charlotte Clarke, Christina Cole, Kerrianne Dempster, Clare Edwards, David Field, Jane Greenaway, Elizabeth Hutchison, Nina Jamieson, Samantha Johnson, Wilf Kelsell, Ann Kennedy, Andy King, Marketa Laube, Louise Linsell, David Murray, Heather O'Connor, Chidubem Okeke Ogwulu, Justine Pepperell, Tracy Roberts, Charles Roehr, Sunil Sinha, Kayleigh Stanbury, Julia Sutton, Richard Welsh, Joy Wiles, Jonathan Wyllie, Edmund Juszczak, Pollyanna Hardy
<p><strong>Background: </strong>In extremely preterm babies, born before 28 weeks' gestation, a large (≥ 1.5 mm in diameter) patent ductus arteriosus present beyond 3 days of age is associated with higher mortality and morbidity than infants without a patent ductus arteriosus. The cyclooxygenase inhibitor ibuprofen may be used to treat patent ductus arteriosus. Whether selective early treatment of a large patent ductus arteriosus with ibuprofen improves health and developmental outcomes is not known.</p><p><strong>Methods: </strong>We conducted a multicentre, randomised, double-blind, placebo-controlled trial evaluating early treatment (≤ 72 hours after birth) with ibuprofen for a large patent ductus arteriosus in extremely preterm infants. The primary outcome was a composite of death or moderate or severe bronchopulmonary dysplasia at 36 weeks' of post menstrual age. The short-term secondary outcomes included complications of prematurity, patent ductus arteriosus closure and side effects of treatment. The main long-term outcome was survival without moderate or severe neurodevelopmental impairment, using parent report or classified by blinded end-point review committee at 24 months of corrected age. Other secondary outcomes included survival without respiratory morbidity and duration of oxygen supplementation. A health economic evaluation was undertaken.</p><p><strong>Results: </strong>A total of 326 infants were randomised to ibuprofen and 327 to placebo. The primary outcome occurred in 220/318 infants (69.2%) in the ibuprofen group and in 202/318 infants (63.5%) in the placebo group (adjusted risk ratio 1.09, 95% confidence interval 0.98 to 1.20; <i>p</i> = 0.10). A total of 44 of 323 infants (13.6%) in the ibuprofen group and 33 of 321 infants (10.3%) in the placebo group died by 36 weeks of gestation (adjusted risk ratio 1.32, 95% confidence interval 0.92 to 1.90). Two unforeseeable serious adverse events occurred that were possibly related to ibuprofen. At 24 months of corrected age, outcome data were available for 263 and 274 children in the ibuprofen and placebo groups, respectively. Survival without moderate to severe neurodevelopmental impairment in the ibuprofen and placebo groups was 131/248 (53.0%) and 134/259 (51.9%), respectively; adjusted risk ratio 1.01 (95% confidence interval 0.86 to 1.18); <i>p</i> = 0.901. Survival without respiratory morbidity was 66/210 (31.4%) and 74/220 (33.6%), respectively; adjusted risk ratio 0.92 (95% confidence interval 0.70 to 1.20); <i>p</i> = 0.536. Median duration of oxygen supplementation was 76.0 and 78.0 days, respectively.</p><p><strong>Conclusion: </strong>The risk of death or moderate or severe bronchopulmonary dysplasia at 36 weeks of post menstrual age was not statistically significantly lower for extremely preterm infants randomised to early treatment with ibuprofen compared to placebo. There was no evidence of an improvement in survival without moderate to severe neurodevelopmental impai
{"title":"Outcome after Selective early treatment for Closure of patent ductus ARteriosus in preterm babies, a multicentre, masked, randomised placebo-controlled parallel group trial (Baby-OSCAR trial).","authors":"Samir Gupta, Nimish V Subhedar, Jennifer L Bell, Ursula Bowler, Charlotte Clarke, Christina Cole, Kerrianne Dempster, Clare Edwards, David Field, Jane Greenaway, Elizabeth Hutchison, Nina Jamieson, Samantha Johnson, Wilf Kelsell, Ann Kennedy, Andy King, Marketa Laube, Louise Linsell, David Murray, Heather O'Connor, Chidubem Okeke Ogwulu, Justine Pepperell, Tracy Roberts, Charles Roehr, Sunil Sinha, Kayleigh Stanbury, Julia Sutton, Richard Welsh, Joy Wiles, Jonathan Wyllie, Edmund Juszczak, Pollyanna Hardy","doi":"10.3310/GJSG2422","DOIUrl":"10.3310/GJSG2422","url":null,"abstract":"<p><strong>Background: </strong>In extremely preterm babies, born before 28 weeks' gestation, a large (≥ 1.5 mm in diameter) patent ductus arteriosus present beyond 3 days of age is associated with higher mortality and morbidity than infants without a patent ductus arteriosus. The cyclooxygenase inhibitor ibuprofen may be used to treat patent ductus arteriosus. Whether selective early treatment of a large patent ductus arteriosus with ibuprofen improves health and developmental outcomes is not known.</p><p><strong>Methods: </strong>We conducted a multicentre, randomised, double-blind, placebo-controlled trial evaluating early treatment (≤ 72 hours after birth) with ibuprofen for a large patent ductus arteriosus in extremely preterm infants. The primary outcome was a composite of death or moderate or severe bronchopulmonary dysplasia at 36 weeks' of post menstrual age. The short-term secondary outcomes included complications of prematurity, patent ductus arteriosus closure and side effects of treatment. The main long-term outcome was survival without moderate or severe neurodevelopmental impairment, using parent report or classified by blinded end-point review committee at 24 months of corrected age. Other secondary outcomes included survival without respiratory morbidity and duration of oxygen supplementation. A health economic evaluation was undertaken.</p><p><strong>Results: </strong>A total of 326 infants were randomised to ibuprofen and 327 to placebo. The primary outcome occurred in 220/318 infants (69.2%) in the ibuprofen group and in 202/318 infants (63.5%) in the placebo group (adjusted risk ratio 1.09, 95% confidence interval 0.98 to 1.20; <i>p</i> = 0.10). A total of 44 of 323 infants (13.6%) in the ibuprofen group and 33 of 321 infants (10.3%) in the placebo group died by 36 weeks of gestation (adjusted risk ratio 1.32, 95% confidence interval 0.92 to 1.90). Two unforeseeable serious adverse events occurred that were possibly related to ibuprofen. At 24 months of corrected age, outcome data were available for 263 and 274 children in the ibuprofen and placebo groups, respectively. Survival without moderate to severe neurodevelopmental impairment in the ibuprofen and placebo groups was 131/248 (53.0%) and 134/259 (51.9%), respectively; adjusted risk ratio 1.01 (95% confidence interval 0.86 to 1.18); <i>p</i> = 0.901. Survival without respiratory morbidity was 66/210 (31.4%) and 74/220 (33.6%), respectively; adjusted risk ratio 0.92 (95% confidence interval 0.70 to 1.20); <i>p</i> = 0.536. Median duration of oxygen supplementation was 76.0 and 78.0 days, respectively.</p><p><strong>Conclusion: </strong>The risk of death or moderate or severe bronchopulmonary dysplasia at 36 weeks of post menstrual age was not statistically significantly lower for extremely preterm infants randomised to early treatment with ibuprofen compared to placebo. There was no evidence of an improvement in survival without moderate to severe neurodevelopmental impai","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":"30 11","pages":"1-17"},"PeriodicalIF":4.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12914754/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146142401","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}
<p><strong>Background: </strong>Behavioural weight management interventions are the main funded interventions for people living with obesity in the United Kingdom, but there is high intervention variability, including mode of delivery, dietary, physical activity and behavioural components.</p><p><strong>Objective: </strong>To map individual components of behavioural weight management interventions used in pragmatic clinical trials and those commissioned in the real world. To decide on the components which vary across the interventions and are hypothesised to be of importance to attendance, completion and weight loss.</p><p><strong>Design: </strong>Cross-sectional survey.</p><p><strong>Setting: </strong>Behavioural weight management interventions in two separate scenarios: randomised controlled trials and real-world services (local authority and commercial).</p><p><strong>Main outcome measure: </strong>Identification of components of interest that demonstrate variation in both settings.</p><p><strong>Methods: </strong>Mapping exercise of randomised controlled trials and real-world services using the standardized reporting of adult behavioural weight management interventions to aid evaluation. Selection of components by expert group consensus derived from online survey and discussion.</p><p><strong>Data sources: </strong>Mapping performed by a local contact for real-world services and by one BECOME researcher for randomised controlled trials. Study expert group provided their opinions via online survey and discussion.</p><p><strong>Results: </strong>Real-world services providing data on 19 services and 6 randomised controlled trials were mapped using an intervention template. Survey and discussion led to expert group consensus of components for analysis within a meta-analysis. Summary descriptions are provided for each programme displaying variability in eligibility and exclusion criteria. Results provide a description of real-world services and randomised controlled trials, demonstrating variation between the programme components, for example, programme delivery (face-to-face group based was the most common answer for 28.6% randomised controlled trials and 63.2% real-world services), setting (community centre was the most common answer for 0% of randomised controlled trials and 69.2% real-world services) and total duration of the programme (12 weeks for 7.1% randomised controlled trials and 57.9% real-world services).</p><p><strong>Limitations: </strong>The standardised reporting template is lengthy and can take up to 1.5 hours to complete. The template for randomised controlled was not completed by the trials themselves. An expert group derived the components of interest, which could produce different results with a different group of people.</p><p><strong>Conclusions: </strong>Our work has provided an example of how standardized reporting of adult behavioural weight management interventions to aid evaluation can be implemented. Interventions we
{"title":"Mapping components of behavioural weight management interventions using electronic survey and component selection by expert consensus: the BE:COME Study.","authors":"Rebecca Gregg, Nishant Jaiswal, Sahar Sharif, Alison Avenell, Louisa Ells, Sandra Jayacodi, Ruth Mackenzie, Sharon Simpson, Olivia Wu, Jennifer Logue","doi":"10.3310/JLGJ1630","DOIUrl":"10.3310/JLGJ1630","url":null,"abstract":"<p><strong>Background: </strong>Behavioural weight management interventions are the main funded interventions for people living with obesity in the United Kingdom, but there is high intervention variability, including mode of delivery, dietary, physical activity and behavioural components.</p><p><strong>Objective: </strong>To map individual components of behavioural weight management interventions used in pragmatic clinical trials and those commissioned in the real world. To decide on the components which vary across the interventions and are hypothesised to be of importance to attendance, completion and weight loss.</p><p><strong>Design: </strong>Cross-sectional survey.</p><p><strong>Setting: </strong>Behavioural weight management interventions in two separate scenarios: randomised controlled trials and real-world services (local authority and commercial).</p><p><strong>Main outcome measure: </strong>Identification of components of interest that demonstrate variation in both settings.</p><p><strong>Methods: </strong>Mapping exercise of randomised controlled trials and real-world services using the standardized reporting of adult behavioural weight management interventions to aid evaluation. Selection of components by expert group consensus derived from online survey and discussion.</p><p><strong>Data sources: </strong>Mapping performed by a local contact for real-world services and by one BECOME researcher for randomised controlled trials. Study expert group provided their opinions via online survey and discussion.</p><p><strong>Results: </strong>Real-world services providing data on 19 services and 6 randomised controlled trials were mapped using an intervention template. Survey and discussion led to expert group consensus of components for analysis within a meta-analysis. Summary descriptions are provided for each programme displaying variability in eligibility and exclusion criteria. Results provide a description of real-world services and randomised controlled trials, demonstrating variation between the programme components, for example, programme delivery (face-to-face group based was the most common answer for 28.6% randomised controlled trials and 63.2% real-world services), setting (community centre was the most common answer for 0% of randomised controlled trials and 69.2% real-world services) and total duration of the programme (12 weeks for 7.1% randomised controlled trials and 57.9% real-world services).</p><p><strong>Limitations: </strong>The standardised reporting template is lengthy and can take up to 1.5 hours to complete. The template for randomised controlled was not completed by the trials themselves. An expert group derived the components of interest, which could produce different results with a different group of people.</p><p><strong>Conclusions: </strong>Our work has provided an example of how standardized reporting of adult behavioural weight management interventions to aid evaluation can be implemented. Interventions we","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":" ","pages":"1-27"},"PeriodicalIF":4.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12951269/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147276220","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：