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":"https://doi.org/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":"","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":"","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":"https://doi.org/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":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Matthew Walton, Alexis Llewellyn, Eleonora Uphoff, Joseph Lord, Melissa Harden, Robert Hodgson, Mark Simmonds
<p><strong>Background: </strong>Skin cancers are some of the most common types of cancer. Dermatology services receive about 1.2 million referrals a year, but only a small minority are confirmed skin cancer. Artificial intelligence may be helpful in the diagnosis of skin cancer by identifying lesions that are or are not cancerous.</p><p><strong>Objectives: </strong>To investigate the clinical and cost-effectiveness of two artificial intelligence technologies: DERM (Deep Ensemble for Recognition of Malignancy, Skin Analytics) and Moleanalyzer Pro (FotoFinder), as decision aids following a primary care referral.</p><p><strong>Methods: </strong>A rapid systematic review of evidence on the two technologies was conducted. A narrative synthesis was performed, with a meta-analysis of diagnostic accuracy data. Published and unpublished cost-effectiveness evidence on the named technologies, as well as other diagnostic technologies were reviewed. A conceptual model was developed that could form the basis of a full economic evaluation.</p><p><strong>Results: </strong>Four studies of DERM and two of Moleanalyzer Pro were subject to full synthesis. DERM had a sensitivity of 96.1% to detect any malignant lesion (95% confidence interval 95.4 to 96.8); at a specificity of 65.4% (95% confidence interval 64.7 to 66.1). For detecting benign lesions, the sensitivity was 71.5% (95% confidence interval 70.7 to 72.3) for a specificity of 86.2% (95% confidence interval 85.4 to 87.0). Moleanalyzer Pro had lower sensitivity, but higher specificity for detecting melanoma than face-to-face dermatologists. DERM might lead to around half of all patients being discharged without assessment by a dermatologist, but a small number of malignant lesions would be missed. Patient and clinical opinions showed substantial resistance to using artificial intelligence without any assessment of lesions by a dermatologist. No published assessments of the cost-effectiveness of the technologies were identified; three assessments related to skin cancer more broadly in a National Health Service setting were identified. These studies employed similar model structures, but the mechanism by which diagnostic accuracy influenced costs and health outcomes differed. An unpublished cost-utility model was provided by Skin Analytics. Several issues with the modelling approach were identified, particularly the mechanisms by which value is driven and how diagnostic accuracy evidence was used. The conceptual model presents an alternative approach, which aligns more closely with the National Institute for Health and Care Excellence reference case and which more appropriately characterises the long-term consequences of basal cell carcinoma.</p><p><strong>Limitations: </strong>The rapid review approach meant that some relevant material may have been missed, and capacity for synthesis was limited. The proposed conceptual model does not capture non-cash benefits associated with demand on dermatologist time. An a
{"title":"Artificial Intelligence technologies for assessing skin lesions for referral on the urgent suspected cancer pathway to detect benign lesions and reduce secondary care specialist appointments: early value assessment.","authors":"Matthew Walton, Alexis Llewellyn, Eleonora Uphoff, Joseph Lord, Melissa Harden, Robert Hodgson, Mark Simmonds","doi":"10.3310/GJMS0317","DOIUrl":"https://doi.org/10.3310/GJMS0317","url":null,"abstract":"<p><strong>Background: </strong>Skin cancers are some of the most common types of cancer. Dermatology services receive about 1.2 million referrals a year, but only a small minority are confirmed skin cancer. Artificial intelligence may be helpful in the diagnosis of skin cancer by identifying lesions that are or are not cancerous.</p><p><strong>Objectives: </strong>To investigate the clinical and cost-effectiveness of two artificial intelligence technologies: DERM (Deep Ensemble for Recognition of Malignancy, Skin Analytics) and Moleanalyzer Pro (FotoFinder), as decision aids following a primary care referral.</p><p><strong>Methods: </strong>A rapid systematic review of evidence on the two technologies was conducted. A narrative synthesis was performed, with a meta-analysis of diagnostic accuracy data. Published and unpublished cost-effectiveness evidence on the named technologies, as well as other diagnostic technologies were reviewed. A conceptual model was developed that could form the basis of a full economic evaluation.</p><p><strong>Results: </strong>Four studies of DERM and two of Moleanalyzer Pro were subject to full synthesis. DERM had a sensitivity of 96.1% to detect any malignant lesion (95% confidence interval 95.4 to 96.8); at a specificity of 65.4% (95% confidence interval 64.7 to 66.1). For detecting benign lesions, the sensitivity was 71.5% (95% confidence interval 70.7 to 72.3) for a specificity of 86.2% (95% confidence interval 85.4 to 87.0). Moleanalyzer Pro had lower sensitivity, but higher specificity for detecting melanoma than face-to-face dermatologists. DERM might lead to around half of all patients being discharged without assessment by a dermatologist, but a small number of malignant lesions would be missed. Patient and clinical opinions showed substantial resistance to using artificial intelligence without any assessment of lesions by a dermatologist. No published assessments of the cost-effectiveness of the technologies were identified; three assessments related to skin cancer more broadly in a National Health Service setting were identified. These studies employed similar model structures, but the mechanism by which diagnostic accuracy influenced costs and health outcomes differed. An unpublished cost-utility model was provided by Skin Analytics. Several issues with the modelling approach were identified, particularly the mechanisms by which value is driven and how diagnostic accuracy evidence was used. The conceptual model presents an alternative approach, which aligns more closely with the National Institute for Health and Care Excellence reference case and which more appropriately characterises the long-term consequences of basal cell carcinoma.</p><p><strong>Limitations: </strong>The rapid review approach meant that some relevant material may have been missed, and capacity for synthesis was limited. The proposed conceptual model does not capture non-cash benefits associated with demand on dermatologist time. An a","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":"30 10","pages":"1-96"},"PeriodicalIF":4.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146142299","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}
Sarah Baos, Terrie Walker-Smith, Mandy Lui, Elizabeth A Stokes, Jingjing Jiang, Maria Pufulete, Ben Gibbison, Chris A Rogers
<p><strong>Background: </strong>Gabapentin is an anticonvulsant medication with a United Kingdom licence to treat partial seizures and neuropathic pain. It is used off-licence for acute pain and is frequently added to multimodal analgesic regimens after surgery to try and reduce opioid use while controlling pain effectively.</p><p><strong>Objective: </strong>To test the hypothesis that gabapentin reduces opioid use after major surgery and speeds up recovery, thereby reducing postoperative hospital length of stay compared to standard multimodal analgesia.</p><p><strong>Design, setting and participants: </strong>The GAP study was a multicentre, blinded, randomised controlled trial in patients aged ≥ 18 years, undergoing cardiac, thoracic or abdominal surgery with an expected postoperative stay of ≥ 2 days in seven National Health Service hospitals. The trial was designed to provide 90% power to detect a difference of 12.5% in the proportion of participants discharged by the median length of stay in <i>each</i> specialty (500 participants/specialty), which was reduced to 80% (340 participants/specialty) due to COVID-19-related recruitment challenges.</p><p><strong>Interventions: </strong>Participants were randomised 1 : 1 (stratified by surgical specialty) to receive either gabapentin (600 mg before surgery, 300 mg twice daily for 2 days after surgery) or placebo as an adjunct to multimodal pain regimens.</p><p><strong>Main outcome measures: </strong>Primary outcome was length of stay. Secondary outcomes included acute and chronic (Brief Pain Inventory) pain, total opioid use, adverse health events, health-related quality of life (-EQ-5D-5L, Short Form questionnaire-12 items physical component score and mental component score), resource use; cost-effectiveness (outcome measure quality-adjusted life-years using EQ-5D, five-level version).</p><p><strong>Results: </strong>One thousand one hundred and ninety-six (cardiac 500, thoracic 346, abdominal 350) participants consented and were randomised. Baseline characteristics were well balanced across the two groups: median age: 68 years; male sex 796/1195 (66.4%). Of the participants, 223/1195 (18.7%) did not receive all prescribed medication or received medication out of window. There was no difference in length of stay; median placebo (<i>n</i> = 589): 6.15, gabapentin (<i>n</i> = 595): 5.94 days [hazard ratio for discharge 1.07, 95% confidence interval (0.95 to 1.20), <i>p</i> = 0.26]. Opioid use <i>in-hospital</i> differed between surgical specialties (<i>p</i> = 0.001); in the abdominal specialty, it was significantly lower in the gabapentin group in 4 of the first 5 postoperative days [range -26% (-46% to 0%) to -36% (-52% to -14%)], with no differences in the cardiac specialty nor in the thoracic specialty beyond day 2. <i>During follow-up</i>, opioid use was similar in the two groups across all specialties. Acute pain beyond 24 hours was similar (<i>p</i> ≥ 0.15). The incidence of one or more serio
{"title":"Gabapentin as an adjunct to multimodal pain regimens in surgical patients: the GAP placebo-controlled RCT and economic evaluation.","authors":"Sarah Baos, Terrie Walker-Smith, Mandy Lui, Elizabeth A Stokes, Jingjing Jiang, Maria Pufulete, Ben Gibbison, Chris A Rogers","doi":"10.3310/PLMH9787","DOIUrl":"https://doi.org/10.3310/PLMH9787","url":null,"abstract":"<p><strong>Background: </strong>Gabapentin is an anticonvulsant medication with a United Kingdom licence to treat partial seizures and neuropathic pain. It is used off-licence for acute pain and is frequently added to multimodal analgesic regimens after surgery to try and reduce opioid use while controlling pain effectively.</p><p><strong>Objective: </strong>To test the hypothesis that gabapentin reduces opioid use after major surgery and speeds up recovery, thereby reducing postoperative hospital length of stay compared to standard multimodal analgesia.</p><p><strong>Design, setting and participants: </strong>The GAP study was a multicentre, blinded, randomised controlled trial in patients aged ≥ 18 years, undergoing cardiac, thoracic or abdominal surgery with an expected postoperative stay of ≥ 2 days in seven National Health Service hospitals. The trial was designed to provide 90% power to detect a difference of 12.5% in the proportion of participants discharged by the median length of stay in <i>each</i> specialty (500 participants/specialty), which was reduced to 80% (340 participants/specialty) due to COVID-19-related recruitment challenges.</p><p><strong>Interventions: </strong>Participants were randomised 1 : 1 (stratified by surgical specialty) to receive either gabapentin (600 mg before surgery, 300 mg twice daily for 2 days after surgery) or placebo as an adjunct to multimodal pain regimens.</p><p><strong>Main outcome measures: </strong>Primary outcome was length of stay. Secondary outcomes included acute and chronic (Brief Pain Inventory) pain, total opioid use, adverse health events, health-related quality of life (-EQ-5D-5L, Short Form questionnaire-12 items physical component score and mental component score), resource use; cost-effectiveness (outcome measure quality-adjusted life-years using EQ-5D, five-level version).</p><p><strong>Results: </strong>One thousand one hundred and ninety-six (cardiac 500, thoracic 346, abdominal 350) participants consented and were randomised. Baseline characteristics were well balanced across the two groups: median age: 68 years; male sex 796/1195 (66.4%). Of the participants, 223/1195 (18.7%) did not receive all prescribed medication or received medication out of window. There was no difference in length of stay; median placebo (<i>n</i> = 589): 6.15, gabapentin (<i>n</i> = 595): 5.94 days [hazard ratio for discharge 1.07, 95% confidence interval (0.95 to 1.20), <i>p</i> = 0.26]. Opioid use <i>in-hospital</i> differed between surgical specialties (<i>p</i> = 0.001); in the abdominal specialty, it was significantly lower in the gabapentin group in 4 of the first 5 postoperative days [range -26% (-46% to 0%) to -36% (-52% to -14%)], with no differences in the cardiac specialty nor in the thoracic specialty beyond day 2. <i>During follow-up</i>, opioid use was similar in the two groups across all specialties. Acute pain beyond 24 hours was similar (<i>p</i> ≥ 0.15). The incidence of one or more serio","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":"30 9","pages":"1-144"},"PeriodicalIF":4.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146142399","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}
Julia Sanders, Christian Barlow, Peter Brocklehurst, Rebecca Cannings-John, Susan Channon, Christopher Gale, Judith Cutter, Jacqueline Hughes, Billie Hunter, Fiona Lugg-Widger, Sarah Milosevic, Rebecca Milton, Leah Morantz, Mary Nolan, Rachel Plachcinski, Shantini Paranjothy, Michael Robling
<p><strong>Background: </strong>Intrapartum water immersion analgesia has been recommended by the National Institute for Health and Care Excellence since 2007, but high-quality evidence relating to the safety of waterbirth for mothers and their babies was lacking.</p><p><strong>Primary study objective: </strong>To establish whether, in the case of 'low-risk' women who use water immersion during labour, waterbirth, compared to birth out of water, is as safe for mothers and their babies.</p><p><strong>Methods: </strong>A cohort study with non-inferiority design.</p><p><strong>Setting: </strong>Twenty-six National Health Service organisations in England and Wales.</p><p><strong>Participants: </strong>The primary analysis included 60,402 births between January 2015 and June 2022. Primary analysis was restricted to births where the woman: (1) was without complicating medical conditions at the time of pool entry, (2) used water immersion during labour and (3) did not receive obstetric or anaesthetic interventions prior to birth. Comparisons were undertaken between women who gave birth in water and women who gave birth out of water.</p><p><strong>Main outcome measures: </strong>Maternal primary outcome: obstetric anal sphincter injury (with planned subgroup analysis by parity); neonatal composite primary outcome: fetal or neonatal death (after the commencement of intrapartum care and prior to discharge home), neonatal unit admission with respiratory support or the administration of intravenous antibiotics within 48 hours of birth. Separate a priori sample size calculations were undertaken for the maternal and neonatal primary outcomes.</p><p><strong>Results: </strong>After adjusting for differences in the characteristics of women who used intrapartum water immersion and gave birth in or out of water: (1) among nulliparous women, rates of recorded obstetric anal sphincter injury were no higher among women who gave birth in water than among women who left the pool before birth [730 of 15,176 women (4.8%) vs. 641 of 12,210 women (5.3%); adjusted odds ratio 0.97; one-sided 95% confidence interval, -∞ to 1.08]; (2) among parous women, rates of recorded obstetric anal sphincter injury were no higher among women who gave birth in water than among women who left the pool before birth [269 of 24,451 women (1.1%) vs. 144 of 8565 women (1.7%); adjusted odds ratio 0.64; -∞ to 0.78]. Among babies, rates of the primary outcome were no higher among babies born in water than among babies born out of water [263 of 9868 infants (2.7%) vs. 224 of 5078 infants (4.4%); adjusted odds ratio, 0.65; -∞ to 0.79]. All upper confidence intervals of the primary outcomes were lower than the prespecified margins of non-inferiority; therefore, we conclude that the rate of the primary outcomes for mothers and their babies were no higher among waterbirths than among births out of water. Rates of the individual components of the neonatal primary outcome were: Intrapartum or neonatal deat
背景：自2007年以来，国家健康与护理卓越研究所（National Institute for Health and Care Excellence）一直推荐分娩时用水浸泡镇痛，但缺乏与母亲及其婴儿水中分娩安全性相关的高质量证据。主要研究目的：确定在分娩过程中使用水浸泡的“低风险”妇女的情况下，与在水中分娩相比，水中分娩对母亲和婴儿是否同样安全。方法：采用非劣效性设计的队列研究。环境：英格兰和威尔士的26个国家卫生服务组织。参与者：主要分析包括2015年1月至2022年6月期间出生的60402人。初步分析仅限于以下情况的分娩：(1)入池时没有复杂的医疗条件，(2)分娩时使用浸泡水，(3)分娩前未接受产科或麻醉干预。对在水中分娩的妇女和不在水中分娩的妇女进行了比较。主要结局指标：产妇主要结局：产科肛门括约肌损伤（按胎次进行计划亚组分析）；新生儿复合主要结局：胎儿或新生儿死亡（在分娩时护理开始后和出院前），新生儿病房在出生后48小时内接受呼吸支持或静脉注射抗生素。对产妇和新生儿的主要结局进行单独的先验样本量计算。结果：在调整了产时用水浸泡和在水中或在水中分娩的妇女的特征差异后：(1)在未分娩妇女中，记录的产科肛门括约肌损伤率在水中分娩的妇女中并不高于出生前离开游泳池的妇女[15,176名妇女中有730名（4.8%）比在12,210名妇女中有641名（5.3%）]；调整优势比0.97；单侧95%置信区间，-∞至1.08]；(2)在分娩妇女中，在水中分娩的妇女的产科肛门括约肌损伤率不高于在出生前离开游泳池的妇女[24,451名妇女中有269名（1.1%）比在8565名妇女中有144名（1.7%）]；调整优势比0.64；-∞至0.78]。在婴儿中，水中出生的婴儿的主要转归率并不高于非水中出生的婴儿[9868例婴儿中有263例（2.7%）对5078例婴儿中有224例（4.4%）；调整后优势比为0.65；-∞到0.79]。所有主要结局的上置信区间均低于预定的非劣效性边际；因此，我们得出结论，水中分娩的母亲及其婴儿的主要结局率并不高于非水中分娩。新生儿主要结局的各个组成部分的比率为：产时或新生儿死亡，发生在水中出生的3名婴儿中(0.3。每1000名新生儿)，而非在水中出生的婴儿则为零。在新生儿病房为91名（0.9%）水中出生的婴儿和104名（2.0%）非水中出生的婴儿提供呼吸支持；（调整优势比0.44，单侧95%置信区间-∞至0.60）。263名（2.7%）水中出生的婴儿和224名（4.4%）非水中出生的婴儿在出生48小时内使用抗生素（调整后的优势比为0.65，-∞至0.79）。在线调查和访谈确定了影响联合王国生育池使用的各种因素，并强调需要解决与资源可用性（包括具有水中分娩经验的助产士）、单位文化和准则以及工作人员认可相关的问题。现场案例研究发现，与助产单位相比，产科单位在设备和资源、工作人员的态度和信心、高级工作人员的支持和妇女对水中分娩的认识方面更不便利。局限性：该研究的局限性包括无法可靠地识别医疗记录中记录的患有医学或产科并发症的妇女，以及不知道或无法调整的组间混淆的可能性，包括离开游泳池的原因。结论：对于没有怀孕和分娩复杂性的妇女，在分娩过程中使用水浸泡，在水中分娩对母亲和婴儿的安全性与在水中分娩一样。这项研究支持政策和实践，使使用产时水浸泡的无并发症妊娠和分娩妇女能够选择留在水中或离开水中分娩。
{"title":"Establishing the safety of waterbirth for mothers and their babies: the POOL cohort study with nested qualitative component.","authors":"Julia Sanders, Christian Barlow, Peter Brocklehurst, Rebecca Cannings-John, Susan Channon, Christopher Gale, Judith Cutter, Jacqueline Hughes, Billie Hunter, Fiona Lugg-Widger, Sarah Milosevic, Rebecca Milton, Leah Morantz, Mary Nolan, Rachel Plachcinski, Shantini Paranjothy, Michael Robling","doi":"10.3310/GGHD6684","DOIUrl":"https://doi.org/10.3310/GGHD6684","url":null,"abstract":"<p><strong>Background: </strong>Intrapartum water immersion analgesia has been recommended by the National Institute for Health and Care Excellence since 2007, but high-quality evidence relating to the safety of waterbirth for mothers and their babies was lacking.</p><p><strong>Primary study objective: </strong>To establish whether, in the case of 'low-risk' women who use water immersion during labour, waterbirth, compared to birth out of water, is as safe for mothers and their babies.</p><p><strong>Methods: </strong>A cohort study with non-inferiority design.</p><p><strong>Setting: </strong>Twenty-six National Health Service organisations in England and Wales.</p><p><strong>Participants: </strong>The primary analysis included 60,402 births between January 2015 and June 2022. Primary analysis was restricted to births where the woman: (1) was without complicating medical conditions at the time of pool entry, (2) used water immersion during labour and (3) did not receive obstetric or anaesthetic interventions prior to birth. Comparisons were undertaken between women who gave birth in water and women who gave birth out of water.</p><p><strong>Main outcome measures: </strong>Maternal primary outcome: obstetric anal sphincter injury (with planned subgroup analysis by parity); neonatal composite primary outcome: fetal or neonatal death (after the commencement of intrapartum care and prior to discharge home), neonatal unit admission with respiratory support or the administration of intravenous antibiotics within 48 hours of birth. Separate a priori sample size calculations were undertaken for the maternal and neonatal primary outcomes.</p><p><strong>Results: </strong>After adjusting for differences in the characteristics of women who used intrapartum water immersion and gave birth in or out of water: (1) among nulliparous women, rates of recorded obstetric anal sphincter injury were no higher among women who gave birth in water than among women who left the pool before birth [730 of 15,176 women (4.8%) vs. 641 of 12,210 women (5.3%); adjusted odds ratio 0.97; one-sided 95% confidence interval, -∞ to 1.08]; (2) among parous women, rates of recorded obstetric anal sphincter injury were no higher among women who gave birth in water than among women who left the pool before birth [269 of 24,451 women (1.1%) vs. 144 of 8565 women (1.7%); adjusted odds ratio 0.64; -∞ to 0.78]. Among babies, rates of the primary outcome were no higher among babies born in water than among babies born out of water [263 of 9868 infants (2.7%) vs. 224 of 5078 infants (4.4%); adjusted odds ratio, 0.65; -∞ to 0.79]. All upper confidence intervals of the primary outcomes were lower than the prespecified margins of non-inferiority; therefore, we conclude that the rate of the primary outcomes for mothers and their babies were no higher among waterbirths than among births out of water. Rates of the individual components of the neonatal primary outcome were: Intrapartum or neonatal deat","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":"30 15","pages":"1-128"},"PeriodicalIF":4.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146142423","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}
Kevin Cooper, Lynda Constable, Thenmalar Vadiveloo, Ayodeji Matuluko, Christine Kennedy, Sharon McCann, Seonaidh Cotton, Katie Gillies, Rebecca Bruce, Paul Smith, Graeme MacLennan, T Justin Clark
<p><strong>Background: </strong>Deep endometriosis causes significant pain which adversely affects quality of life and utilises healthcare and wider societal resources. Laparoscopic excision of endometriosis has shown to improve pain symptoms in observational series but 1 in 14 patients experience serious surgical complications. Medical management centres around hormonal treatment, which is less risky and has been shown to be efficacious but can cause troublesome side effects and is incompatible with conception. There are no randomised controlled trials providing conclusive comparative evidence on clinical and cost-effectiveness of these treatments.</p><p><strong>Objective(s): </strong>To compare the clinical and cost-effectiveness of laparoscopic surgery versus optimised medical treatment for managing deep endometriosis.</p><p><strong>Design and methods: </strong>A multicentre randomised controlled trial, with an internal pilot phase, and economic evaluation, to compare early planned laparoscopic surgery (first attempt at definitive surgery) with or without adjuvant medical treatment versus optimised medical management alone in women with deep endometriosis.</p><p><strong>Setting and participants: </strong>Women presenting with pelvic pain associated with surgically or radiologically confirmed deep endometriosis, suitable for either surgical or medical management, recruited and managed at accredited British Society for Gynaecological Endoscopy Endometriosis Centres.</p><p><strong>Interventions: </strong>Early planned laparoscopic surgery to excise deep endometriosis (with or without medical treatment) or medical management alone.</p><p><strong>Main outcome measures: </strong>The primary outcome was condition-specific quality of life measured using the pain domain of the Endometriosis Health Profile-30 at 18 months post randomisation. The primary health economic outcome was to be incremental cost per quality-adjusted life-year gained at 18 months. Secondary outcomes included quality of life (Endometriosis Health Profile-30), pain, complications, occupational and reproductive outcomes.</p><p><strong>Results: </strong>Three hundred and seventy-seven patients were screened, 103 were eligible and 18 were randomised. Of the eight patients allocated surgery, only one had had their surgery by the time of trial closure and six participants (2/4, 50% allocated surgery and 4/8, 50% allocated medical treatment) had reached the first trial end point at 3 months. No participant reached the primary outcome at 18 months post randomisation.</p><p><strong>Limitations: </strong>The overriding limitation was failure to recruit participants at a satisfactory rate resulting in a final sample of only 18 patients with a target of 320 (inflated to 400 to account for a projected 20% attrition rate). Given the nature of the intervention, it was not possible to blind either the care providers, investigators or participants to their allocated group.</p><p><strong>Conclusion
{"title":"Clinical and cost-effectiveness of medical management versus surgery for deep infiltrating endometriosis: synopsis from the DIAMOND RCT.","authors":"Kevin Cooper, Lynda Constable, Thenmalar Vadiveloo, Ayodeji Matuluko, Christine Kennedy, Sharon McCann, Seonaidh Cotton, Katie Gillies, Rebecca Bruce, Paul Smith, Graeme MacLennan, T Justin Clark","doi":"10.3310/GJKC5715","DOIUrl":"https://doi.org/10.3310/GJKC5715","url":null,"abstract":"<p><strong>Background: </strong>Deep endometriosis causes significant pain which adversely affects quality of life and utilises healthcare and wider societal resources. Laparoscopic excision of endometriosis has shown to improve pain symptoms in observational series but 1 in 14 patients experience serious surgical complications. Medical management centres around hormonal treatment, which is less risky and has been shown to be efficacious but can cause troublesome side effects and is incompatible with conception. There are no randomised controlled trials providing conclusive comparative evidence on clinical and cost-effectiveness of these treatments.</p><p><strong>Objective(s): </strong>To compare the clinical and cost-effectiveness of laparoscopic surgery versus optimised medical treatment for managing deep endometriosis.</p><p><strong>Design and methods: </strong>A multicentre randomised controlled trial, with an internal pilot phase, and economic evaluation, to compare early planned laparoscopic surgery (first attempt at definitive surgery) with or without adjuvant medical treatment versus optimised medical management alone in women with deep endometriosis.</p><p><strong>Setting and participants: </strong>Women presenting with pelvic pain associated with surgically or radiologically confirmed deep endometriosis, suitable for either surgical or medical management, recruited and managed at accredited British Society for Gynaecological Endoscopy Endometriosis Centres.</p><p><strong>Interventions: </strong>Early planned laparoscopic surgery to excise deep endometriosis (with or without medical treatment) or medical management alone.</p><p><strong>Main outcome measures: </strong>The primary outcome was condition-specific quality of life measured using the pain domain of the Endometriosis Health Profile-30 at 18 months post randomisation. The primary health economic outcome was to be incremental cost per quality-adjusted life-year gained at 18 months. Secondary outcomes included quality of life (Endometriosis Health Profile-30), pain, complications, occupational and reproductive outcomes.</p><p><strong>Results: </strong>Three hundred and seventy-seven patients were screened, 103 were eligible and 18 were randomised. Of the eight patients allocated surgery, only one had had their surgery by the time of trial closure and six participants (2/4, 50% allocated surgery and 4/8, 50% allocated medical treatment) had reached the first trial end point at 3 months. No participant reached the primary outcome at 18 months post randomisation.</p><p><strong>Limitations: </strong>The overriding limitation was failure to recruit participants at a satisfactory rate resulting in a final sample of only 18 patients with a target of 320 (inflated to 400 to account for a projected 20% attrition rate). Given the nature of the intervention, it was not possible to blind either the care providers, investigators or participants to their allocated group.</p><p><strong>Conclusion","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":" ","pages":"1-27"},"PeriodicalIF":4.0,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146099599","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}
Gwenllian Wynne-Jones, Martyn Lewis, Gail Sowden, Ira Madan, Karen Walker-Bone, Carolyn A Chew-Graham, Kieran Bromley, Sue Jowett, Vaughan Parsons, Gemma Mansell, Kendra Cooke, Benjamin Saunders, Rosie Harrison, Sarah A Lawton, Simon Wathall, John Pemberton, Julia Hammond, Cyrus Cooper, And Nadine E Foster
Background and objectives: To describe exploratory findings and lessons learned from the discontinued WAVE trial, which sought to determine the effectiveness and costs of adding an early vocational advice intervention to usual primary care on number of days of sickness absence over 6 months.
Methods: Pragmatic, multicentre, two-parallel arm, superiority, randomised controlled trial with health economic analysis in 10 general practices in England, with nested qualitative interviews. Population: Adults with fit notes for any health condition, absent from work ≥ 2 weeks and ≤ 6 months were invited to participate. Intervention and comparator: Participants were randomised (1 : 1) to usual primary care with/without vocational advice delivered by trained Vocational Support Workers. The planned sample size was 720, the first 4 months of recruitment served as an internal pilot phase and the primary outcome was self-reported days of work absence over 6 months.
Results: One hundred and thirty participants were recruited from 7955 invitations (May 2022-May 2023) before trial closure (64 usual care, 66 usual care plus vocational advice). Exploratory analysis of 125 participants (with outcome data) indicated small additional benefits of the vocational advice intervention over usual care [mean days absence = 37.86 (standard deviation = 48.76) vs. usual care = 42.66 (standard deviation = 57.67), incidence rate ratio = 0.913, 80% confidence interval (0.653 to 1.276)]. The vocational advice intervention was delivered remotely [mean = 4.8 contacts (range 1-12)]. Partial health economic evaluation found lower work productivity losses at 6 months after vocational advice intervention (£5513.84, standard deviation = £7101.43) compared to usual care (£6146.21, standard deviation = £8431.88).
Conclusions, limitations and future work: Exploratory analysis indicated a signal of effect, with differences in the number of days absent from work, costs and secondary outcomes. Key lessons learned included the need for closer working with primary care teams and more flexible recruitment methods. A future fully powered randomised controlled trial of vocational advice intervention added to usual primary care is needed to determine the effectiveness and cost-effectiveness.
Funding: This article presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number 17/94/49.
{"title":"Addition of early vocational advice to usual primary care on sickness absence in employed adults: exploratory findings from the discontinued WAVE Randomised Controlled Trial.","authors":"Gwenllian Wynne-Jones, Martyn Lewis, Gail Sowden, Ira Madan, Karen Walker-Bone, Carolyn A Chew-Graham, Kieran Bromley, Sue Jowett, Vaughan Parsons, Gemma Mansell, Kendra Cooke, Benjamin Saunders, Rosie Harrison, Sarah A Lawton, Simon Wathall, John Pemberton, Julia Hammond, Cyrus Cooper, And Nadine E Foster","doi":"10.3310/SVEG8456","DOIUrl":"https://doi.org/10.3310/SVEG8456","url":null,"abstract":"<p><strong>Background and objectives: </strong>To describe exploratory findings and lessons learned from the discontinued WAVE trial, which sought to determine the effectiveness and costs of adding an early vocational advice intervention to usual primary care on number of days of sickness absence over 6 months.</p><p><strong>Methods: </strong>Pragmatic, multicentre, two-parallel arm, superiority, randomised controlled trial with health economic analysis in 10 general practices in England, with nested qualitative interviews. Population: Adults with fit notes for any health condition, absent from work ≥ 2 weeks and ≤ 6 months were invited to participate. Intervention and comparator: Participants were randomised (1 : 1) to usual primary care with/without vocational advice delivered by trained Vocational Support Workers. The planned sample size was 720, the first 4 months of recruitment served as an internal pilot phase and the primary outcome was self-reported days of work absence over 6 months.</p><p><strong>Results: </strong>One hundred and thirty participants were recruited from 7955 invitations (May 2022-May 2023) before trial closure (64 usual care, 66 usual care plus vocational advice). Exploratory analysis of 125 participants (with outcome data) indicated small additional benefits of the vocational advice intervention over usual care [mean days absence = 37.86 (standard deviation = 48.76) vs. usual care = 42.66 (standard deviation = 57.67), incidence rate ratio = 0.913, 80% confidence interval (0.653 to 1.276)]. The vocational advice intervention was delivered remotely [mean = 4.8 contacts (range 1-12)]. Partial health economic evaluation found lower work productivity losses at 6 months after vocational advice intervention (£5513.84, standard deviation = £7101.43) compared to usual care (£6146.21, standard deviation = £8431.88).</p><p><strong>Conclusions, limitations and future work: </strong>Exploratory analysis indicated a signal of effect, with differences in the number of days absent from work, costs and secondary outcomes. Key lessons learned included the need for closer working with primary care teams and more flexible recruitment methods. A future fully powered randomised controlled trial of vocational advice intervention added to usual primary care is needed to determine the effectiveness and cost-effectiveness.</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 17/94/49.</p>","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":" ","pages":"1-32"},"PeriodicalIF":4.0,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146100155","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}
Katie Scandrett, Jacqueline Dinnes, Breanna Morrison, April Coombe, Ridhi Agarwal, Isaac Adu Asare, Phoebe Mead, Andy De Souza, David Elliman, Silvia Lombardo, John Marshall, Sian Taylor-Phillips, Yemisi Takwoingi
<p><strong>Background: </strong>Newborn bloodspot screening offers the potential to detect rare diseases early, enabling timely treatment that can reduce mortality and morbidity. Generating evidence for rare diseases often depends on observational data, making it challenging to formulate recommendations for new screening programmes and evaluate the effectiveness of existing ones.</p><p><strong>Objective(s): </strong>To identify the range of methods and mechanisms used to measure and monitor outcomes from newborn screening programmes using a scoping review.</p><p><strong>Methods: </strong>We included studies published between 2019 and 2024, which evaluated a current or candidate newborn screening programme, or which reported outcomes in screen-detected cases. Studies were categorised into four groups: group 1 reported a comparison and follow-up; group 2 reported a comparison but no follow-up; group 3 reported no comparison with follow-up; and group 4 reported no comparison or follow-up. Data were extracted from a random sample of studies within each group; studies in group 1 were prioritised. Results were reported narratively according to study group. The review was conducted and reported according to current guidance for scoping reviews.</p><p><strong>Data sources: </strong>EMBASE (Ovid), MEDLINE (Ovid) and Science Citation Index (Web of Science - Clarivate).</p><p><strong>Results: </strong>We included 574 primary studies and extracted data from 178. Of the 75 studies in group 1, most compared screen-detected cases with controls (74%). Studies in this group used newborn bloodspot programme databases, registries or record review to identify participants and outcomes; only six (8%) reported use of record linkage. Studies in group 2 (<i>n</i> = 31) mostly reported comparisons of screening tests (25, 81%). Over half of studies in group 3 (<i>n</i> = 34) used newborn bloodspot programme databases to identify participants (53%) and outcomes (65%). A similar pattern was seen in the group 4 (<i>n</i> = 38). Studies reporting follow-up typically relied on retrospective record review or were not well reported. Across all study groups, data on accuracy, epidemiology and genetic variants were common. Studies in group 1 also reported on the effectiveness of newborn bloodspot screening (32/75, 43%), treatment effectiveness (20%) or harms of newborn bloodspot screening (3%).</p><p><strong>Limitations: </strong>Restricting data extraction to a random sample of studies risks missing novel methods or mechanisms.</p><p><strong>Conclusions: </strong>Many studies reported test accuracy metrics and genetic variants in newborn screening. Some data on programme effectiveness were identified, but assessment of potential harms remains limited, and methods for follow-up were poorly reported. Assessment of harms, including overdiagnosis and psychological impact, is crucial to ensuring a net benefit at the population level.</p><p><strong>Future work: </strong>In a second pha
背景：新生儿血斑筛查提供了早期发现罕见疾病的潜力，使及时治疗能够降低死亡率和发病率。为罕见病提供证据往往依赖于观察数据，因此很难为新的筛查方案提出建议，也很难评估现有方案的有效性。目的：通过范围审查确定用于测量和监测新生儿筛查项目结果的方法和机制的范围。方法：我们纳入了2019年至2024年间发表的研究，这些研究评估了当前或候选的新生儿筛查项目，或报告了筛查检测病例的结果。研究分为四组：第一组报告了比较和随访；第二组报告了比较，但没有随访；第三组无随访比较；第4组没有进行比较或随访。数据从每组的随机研究样本中提取；第一组的研究被优先考虑。结果按研究组分组记叙。审查是根据当前范围审查指南进行和报告的。数据来源：EMBASE (Ovid), MEDLINE （Ovid）和Science Citation Index （Web of Science - Clarivate）。结果：我们纳入了574项初步研究，提取了178项数据。在第一组的75项研究中，大多数将筛查检测到的病例与对照组进行比较（74%）。该组研究使用新生儿血斑规划数据库、登记处或记录审查来确定参与者和结果；只有6个（8%）报告使用了记录链接。第2组（n = 31）的研究大多报告了筛查试验的比较（25.81%）。第3组中超过一半的研究（n = 34）使用新生儿血斑规划数据库来确定参与者（53%）和结果（65%）。第4组（n = 38）也出现了类似的情况。报告随访的研究通常依赖于回顾性记录审查或没有得到很好的报道。在所有研究组中，准确性、流行病学和遗传变异的数据都很常见。第1组的研究还报告了新生儿血斑筛查的有效性（32/ 75,43 %）、治疗有效性（20%）或新生儿血斑筛查的危害（3%）。局限性：将数据提取限制在随机的研究样本中，可能会错过新的方法或机制。结论：许多研究报告了新生儿筛查的测试准确性指标和遗传变异。确定了一些关于方案有效性的数据，但对潜在危害的评估仍然有限，后续行动的方法报告也很差。评估危害，包括过度诊断和心理影响，对于确保在人口层面上获得净效益至关重要。未来的工作：在第二阶段的工作中，将对使用不同方法和机制的研究进行深入评估，以确定它们可以提供结果数据的程度，从而为正在进行的和候选筛选计划的评估提供信息。资助：本文介绍了由国家卫生与保健研究所（NIHR）卫生技术评估计划资助的独立研究，奖励号为NIHR167910。
{"title":"Methods and mechanisms for measuring and monitoring outcomes from newborn bloodspot screening: a scoping review.","authors":"Katie Scandrett, Jacqueline Dinnes, Breanna Morrison, April Coombe, Ridhi Agarwal, Isaac Adu Asare, Phoebe Mead, Andy De Souza, David Elliman, Silvia Lombardo, John Marshall, Sian Taylor-Phillips, Yemisi Takwoingi","doi":"10.3310/GJJD1717","DOIUrl":"10.3310/GJJD1717","url":null,"abstract":"<p><strong>Background: </strong>Newborn bloodspot screening offers the potential to detect rare diseases early, enabling timely treatment that can reduce mortality and morbidity. Generating evidence for rare diseases often depends on observational data, making it challenging to formulate recommendations for new screening programmes and evaluate the effectiveness of existing ones.</p><p><strong>Objective(s): </strong>To identify the range of methods and mechanisms used to measure and monitor outcomes from newborn screening programmes using a scoping review.</p><p><strong>Methods: </strong>We included studies published between 2019 and 2024, which evaluated a current or candidate newborn screening programme, or which reported outcomes in screen-detected cases. Studies were categorised into four groups: group 1 reported a comparison and follow-up; group 2 reported a comparison but no follow-up; group 3 reported no comparison with follow-up; and group 4 reported no comparison or follow-up. Data were extracted from a random sample of studies within each group; studies in group 1 were prioritised. Results were reported narratively according to study group. The review was conducted and reported according to current guidance for scoping reviews.</p><p><strong>Data sources: </strong>EMBASE (Ovid), MEDLINE (Ovid) and Science Citation Index (Web of Science - Clarivate).</p><p><strong>Results: </strong>We included 574 primary studies and extracted data from 178. Of the 75 studies in group 1, most compared screen-detected cases with controls (74%). Studies in this group used newborn bloodspot programme databases, registries or record review to identify participants and outcomes; only six (8%) reported use of record linkage. Studies in group 2 (<i>n</i> = 31) mostly reported comparisons of screening tests (25, 81%). Over half of studies in group 3 (<i>n</i> = 34) used newborn bloodspot programme databases to identify participants (53%) and outcomes (65%). A similar pattern was seen in the group 4 (<i>n</i> = 38). Studies reporting follow-up typically relied on retrospective record review or were not well reported. Across all study groups, data on accuracy, epidemiology and genetic variants were common. Studies in group 1 also reported on the effectiveness of newborn bloodspot screening (32/75, 43%), treatment effectiveness (20%) or harms of newborn bloodspot screening (3%).</p><p><strong>Limitations: </strong>Restricting data extraction to a random sample of studies risks missing novel methods or mechanisms.</p><p><strong>Conclusions: </strong>Many studies reported test accuracy metrics and genetic variants in newborn screening. Some data on programme effectiveness were identified, but assessment of potential harms remains limited, and methods for follow-up were poorly reported. Assessment of harms, including overdiagnosis and psychological impact, is crucial to ensuring a net benefit at the population level.</p><p><strong>Future work: </strong>In a second pha","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":" ","pages":"1-48"},"PeriodicalIF":4.0,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12862532/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146046461","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}
Timothy S Walsh, Richard A Parker, Leanne M Aitken, Cathrine A McKenzie, Robert Glen, Christopher J Weir
<p><strong>Background: </strong>Optimising comfort and ability to communicate for mechanically ventilated intensive care unit patients is a priority for clinicians, intensive care unit patients and their relatives. Current usual care is propofol-based sedation plus an opioid analgesic. The alpha2-agonists dexmedetomidine and clonidine are potential alternative sedatives.</p><p><strong>Objective(s): </strong>To explore whether nurses and relatives perceive patients sedated with dexmedetomidine and/or clonidine appear more awake, comfortable and co-operative than patients receiving only propofol-based sedation.</p><p><strong>Design and methods: </strong>Substudy within an open-label, three-arm trial.</p><p><strong>Setting and participants: </strong>Forty-one intensive care units in the United Kingdom. One thousand four hundred and thirty-seven adults receiving propofol ± opioid for sedation-analgesia within 48 hours of starting mechanical ventilation, expected to require ≥ 48 total hours of mechanical ventilation.</p><p><strong>Interventions: </strong>Light sedation was targeted in all patients unless clinicians requested deeper sedation. In intervention groups, algorithms promoted alpha2-agonist up-titration and propofol down-titration, followed by sedation primarily with allocated alpha2-agonist. Usual care was propofol-based sedation. Intervention continued until patients were successfully extubated (primary outcome), or other pre-defined end points.</p><p><strong>Outcomes: </strong>For each 12-hour care period, nurses responded to two 'yes/no' questions: <i>is the patient able to communicate pain? Is the patient able to co-operate with care?</i> When the patients' personal legal representative visited, they were asked for 'yes/no' responses to three questions: <i>does the patient appear awake? Does the patient appear comfortable? Does the visitor feel they can communicate with the patient?</i> Intervention versus propofol group responses were compared fitting a generalised linear mixed model, with results expressed as odds ratios (95% confidence intervals); odds ratios > 1 indicated greater probability of a 'yes' response.</p><p><strong>Results: </strong>Nurse responses were available for > 90% of trial patients [mean (standard deviation) 12 (12) care periods per patient]. Comparing dexmedetomidine versus propofol groups, the odds ratio for a 'yes' response to '<i>communicate pain</i>' was 1.38 (95% confidence interval 1.08 to 1.75), and for clonidine versus propofol, it was 1.13 (0.89 to 1.43). For '<i>co-operate with care</i>' comparing dexmedetomidine versus propofol groups, the odds ratio was 1.14 (95% confidence interval 0.98 to 1.32), and for clonidine versus propofol, it was 0.96 (95% confidence interval 0.83 to 1.12). Relative responses were available for 32-34% of trial patients across groups [mean (standard deviation) 3 (3) days per patient]. For the '<i>appear awake</i>' question, the dexmedetomidine versus propofol group odds ratio
{"title":"Relative and bedside nurse assessment of comfort and communication during propofol, dexmedetomidine, or clonidine-based sedation: pre-planned analysis within the A2B RCT.","authors":"Timothy S Walsh, Richard A Parker, Leanne M Aitken, Cathrine A McKenzie, Robert Glen, Christopher J Weir","doi":"10.3310/GJTW2718","DOIUrl":"10.3310/GJTW2718","url":null,"abstract":"<p><strong>Background: </strong>Optimising comfort and ability to communicate for mechanically ventilated intensive care unit patients is a priority for clinicians, intensive care unit patients and their relatives. Current usual care is propofol-based sedation plus an opioid analgesic. The alpha2-agonists dexmedetomidine and clonidine are potential alternative sedatives.</p><p><strong>Objective(s): </strong>To explore whether nurses and relatives perceive patients sedated with dexmedetomidine and/or clonidine appear more awake, comfortable and co-operative than patients receiving only propofol-based sedation.</p><p><strong>Design and methods: </strong>Substudy within an open-label, three-arm trial.</p><p><strong>Setting and participants: </strong>Forty-one intensive care units in the United Kingdom. One thousand four hundred and thirty-seven adults receiving propofol ± opioid for sedation-analgesia within 48 hours of starting mechanical ventilation, expected to require ≥ 48 total hours of mechanical ventilation.</p><p><strong>Interventions: </strong>Light sedation was targeted in all patients unless clinicians requested deeper sedation. In intervention groups, algorithms promoted alpha2-agonist up-titration and propofol down-titration, followed by sedation primarily with allocated alpha2-agonist. Usual care was propofol-based sedation. Intervention continued until patients were successfully extubated (primary outcome), or other pre-defined end points.</p><p><strong>Outcomes: </strong>For each 12-hour care period, nurses responded to two 'yes/no' questions: <i>is the patient able to communicate pain? Is the patient able to co-operate with care?</i> When the patients' personal legal representative visited, they were asked for 'yes/no' responses to three questions: <i>does the patient appear awake? Does the patient appear comfortable? Does the visitor feel they can communicate with the patient?</i> Intervention versus propofol group responses were compared fitting a generalised linear mixed model, with results expressed as odds ratios (95% confidence intervals); odds ratios > 1 indicated greater probability of a 'yes' response.</p><p><strong>Results: </strong>Nurse responses were available for > 90% of trial patients [mean (standard deviation) 12 (12) care periods per patient]. Comparing dexmedetomidine versus propofol groups, the odds ratio for a 'yes' response to '<i>communicate pain</i>' was 1.38 (95% confidence interval 1.08 to 1.75), and for clonidine versus propofol, it was 1.13 (0.89 to 1.43). For '<i>co-operate with care</i>' comparing dexmedetomidine versus propofol groups, the odds ratio was 1.14 (95% confidence interval 0.98 to 1.32), and for clonidine versus propofol, it was 0.96 (95% confidence interval 0.83 to 1.12). Relative responses were available for 32-34% of trial patients across groups [mean (standard deviation) 3 (3) days per patient]. For the '<i>appear awake</i>' question, the dexmedetomidine versus propofol group odds ratio ","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":" ","pages":"1-18"},"PeriodicalIF":4.0,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12862536/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145997903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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