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":"","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}
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":"https://doi.org/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":"","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":"","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":"https://doi.org/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":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
T Justin Clark, Lina Antoun, Rebecca Woolley, Sheriden Bevan, Kamila Ziomek, William McKinnon, Paul Smith, Kevin Cooper, Ertan Saridogan, Bibi Zeyah Sairally, Jayne Fullard, Monique Morgan, Lynsay Matthews, Laura Jones, Tracy Roberts, Lee Middleton
<p><strong>Background: </strong>The comparative rates of major complications and recovery times between laparoscopic hysterectomy and abdominal hysterectomy for benign gynaecological conditions remain uncertain.</p><p><strong>Objective(s): </strong>To assess the clinical and cost-effectiveness of laparoscopic hysterectomy compared to abdominal hysterectomy in women with benign gynaecological conditions.</p><p><strong>Design and methods: </strong>A parallel, open, non-inferiority, multicentre, randomised controlled, expertise-based surgery trial with integrated health economic evaluation and an internal pilot with an embedded qualitative process evaluation, and a post-closure survey after recruitment ended.</p><p><strong>Setting and participants: </strong>Women in secondary care requiring hysterectomy and eligible for either surgical method.</p><p><strong>Interventions: </strong>Laparoscopic hysterectomy versus abdominal hysterectomy.</p><p><strong>Main outcome measures: </strong>The primary outcome was major complications (Clavien-Dindo ≥ level III) up to 6 completed weeks post surgery, and the key secondary outcome was time from surgery to resumption of usual activities using the personalised Patient-Reported Outcomes Measurement Information System Physical Function questionnaire. The principal outcome for the economic evaluation was to be cost per quality-adjusted life-year at 12 months post surgery and was feasibility and acceptability for the qualitative process evaluation.</p><p><strong>Results: </strong>Two hundred and fifty-two patients were screened from 13 open sites over 13 months, 156 (62%) were eligible and 75 (49%) randomised. Of the 53 women not randomised, 23 (43%) preferred laparoscopic hysterectomy and 6 (11%) abdominal hysterectomy. About 32/39 (82%) and 30/36 (83%) participants randomised to laparoscopic hysterectomy and abdominal hysterectomy, respectively, had their surgery, of which 31/32 (97%) and 25/30 (83%) received their allocated route of hysterectomy. Major complications occurred in 2/32 (6%) laparoscopic hysterectomy versus 4/30 (13%) abdominal hysterectomy groups. There was no difference in time to resumption of activities [median (interquartile range, <i>N</i>) 7.5 weeks (3.6-8.2, 25) laparoscopic hysterectomy vs. 7.5 weeks (5.5-10.6, 26) abdominal hysterectomy groups] or quality of recovery [mean (standard deviation, <i>N</i>) 81.1 (13.4, 27) vs. 72.3 (17.6, 22) respectively; adjusted mean difference 7.2, 95% confidence interval -3.2 to 17.6]. The qualitative evaluation found that the trial was viewed positively by women and healthcare professionals. The reasons for failure to recruit from 21 sites open or in set-up were lack of research/clinical capacity imposed by the COVID-19 pandemic (14, 67%) and lack of clinician equipoise (11, 52%).</p><p><strong>Limitations: </strong>The main limitation was failure to recruit, resulting in a final sample of 75 patients from a target of 3250. At the time of analysis, 13 (17%
{"title":"Laparoscopic hysterectomy versus open abdominal hysterectomy for women with a benign gynaecological condition: the LAVA RCT.","authors":"T Justin Clark, Lina Antoun, Rebecca Woolley, Sheriden Bevan, Kamila Ziomek, William McKinnon, Paul Smith, Kevin Cooper, Ertan Saridogan, Bibi Zeyah Sairally, Jayne Fullard, Monique Morgan, Lynsay Matthews, Laura Jones, Tracy Roberts, Lee Middleton","doi":"10.3310/GJTC1718","DOIUrl":"https://doi.org/10.3310/GJTC1718","url":null,"abstract":"<p><strong>Background: </strong>The comparative rates of major complications and recovery times between laparoscopic hysterectomy and abdominal hysterectomy for benign gynaecological conditions remain uncertain.</p><p><strong>Objective(s): </strong>To assess the clinical and cost-effectiveness of laparoscopic hysterectomy compared to abdominal hysterectomy in women with benign gynaecological conditions.</p><p><strong>Design and methods: </strong>A parallel, open, non-inferiority, multicentre, randomised controlled, expertise-based surgery trial with integrated health economic evaluation and an internal pilot with an embedded qualitative process evaluation, and a post-closure survey after recruitment ended.</p><p><strong>Setting and participants: </strong>Women in secondary care requiring hysterectomy and eligible for either surgical method.</p><p><strong>Interventions: </strong>Laparoscopic hysterectomy versus abdominal hysterectomy.</p><p><strong>Main outcome measures: </strong>The primary outcome was major complications (Clavien-Dindo ≥ level III) up to 6 completed weeks post surgery, and the key secondary outcome was time from surgery to resumption of usual activities using the personalised Patient-Reported Outcomes Measurement Information System Physical Function questionnaire. The principal outcome for the economic evaluation was to be cost per quality-adjusted life-year at 12 months post surgery and was feasibility and acceptability for the qualitative process evaluation.</p><p><strong>Results: </strong>Two hundred and fifty-two patients were screened from 13 open sites over 13 months, 156 (62%) were eligible and 75 (49%) randomised. Of the 53 women not randomised, 23 (43%) preferred laparoscopic hysterectomy and 6 (11%) abdominal hysterectomy. About 32/39 (82%) and 30/36 (83%) participants randomised to laparoscopic hysterectomy and abdominal hysterectomy, respectively, had their surgery, of which 31/32 (97%) and 25/30 (83%) received their allocated route of hysterectomy. Major complications occurred in 2/32 (6%) laparoscopic hysterectomy versus 4/30 (13%) abdominal hysterectomy groups. There was no difference in time to resumption of activities [median (interquartile range, <i>N</i>) 7.5 weeks (3.6-8.2, 25) laparoscopic hysterectomy vs. 7.5 weeks (5.5-10.6, 26) abdominal hysterectomy groups] or quality of recovery [mean (standard deviation, <i>N</i>) 81.1 (13.4, 27) vs. 72.3 (17.6, 22) respectively; adjusted mean difference 7.2, 95% confidence interval -3.2 to 17.6]. The qualitative evaluation found that the trial was viewed positively by women and healthcare professionals. The reasons for failure to recruit from 21 sites open or in set-up were lack of research/clinical capacity imposed by the COVID-19 pandemic (14, 67%) and lack of clinician equipoise (11, 52%).</p><p><strong>Limitations: </strong>The main limitation was failure to recruit, resulting in a final sample of 75 patients from a target of 3250. At the time of analysis, 13 (17%","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":"30 14","pages":"1-27"},"PeriodicalIF":4.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146149682","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}
Ben Shelley, Lee Middleton, Andreas Goebel, Stephen Grant, Louise Jackson, Mishal Javed, Marcus Jepson, Nandor Marczin, Rajnikant Mehta, Teresa Melody, Babu Naidu, Hannah Summers, Lajos Szentgyorgyi, Sarah Tearne, Ben Watkins, Matthew Wilson, Andrew Worrall, Joyce Yeung, Fang Gao Smith
<p><strong>Background: </strong>More than a third of patients undergoing thoracotomy suffer from debilitating chronic post-thoracotomy pain lasting months or years postoperatively. Aggressive management of acute pain during the perioperative period may mitigate this risk.</p><p><strong>Objective(s): </strong>To determine the clinical and cost-effectiveness of paravertebral blockade compared to thoracic epidural blockade, by testing the hypothesis that paravertebral blockade reduces the incidence of chronic post-thoracotomy pain.</p><p><strong>Design and methods: </strong>A parallel, open, multicentre, randomised controlled with integrated health-economic evaluation and an internal pilot that incorporated a qualitative recruitment intervention.</p><p><strong>Setting and participants: </strong>Adult patients undergoing thoracotomy in 15 United Kingdom centres.</p><p><strong>Interventions: </strong>Paravertebral blockade compared to thoracic epidural blockade.</p><p><strong>Main outcome measures: </strong>The primary outcome was the presence of chronic post-thoracotomy pain at 6 months post randomisation defined as 'worst chest pain over the last week' of at least moderate intensity, with a visual analogue scale score ≥ 40 mm. Secondary outcomes included visual analogue scale pain scores in the acute (days 1, 2, 3 and discharge) and chronic (3, 6 and 12 months) phases postoperatively; Brief Pain Inventory; Short Form McGill Pain Questionnaire 2; Hospital Anxiety and Depression Scale; patient satisfaction; analgesia use in the acute and chronic phases; complications (analgesic, surgical and pulmonary) and mortality. For the economic evaluation, the EuroQol-5 Dimensions, five-level version questionnaire was utilised.</p><p><strong>Results: </strong>Between 8 January 2019 and 29 September 2023, 770 patients underwent randomisation; 33 did not proceed to thoracotomy. At 6 months, 59 (22%) of 272 participants in the paravertebral blockade group and 47 (16%) of 292 in the thoracic epidural blockade group developed chronic pain [adjusted risk ratio = 1.32 (95% confidence interval 0.93 to 1.86); adjusted risk difference = 0.05 (95% confidence interval -0.01 to 0.11); <i>p</i> = 0.12]. During the acute phase, both worst and average pain was higher on day 1 with paravertebral blockade [adjusted mean difference 7.7 mm (95% confidence interval 2.8 to 12.5) and 7.0 mm (95% confidence interval 2.7 to 11.2), respectively] but not different on days 2 and 3. Hypotension was less common in the paravertebral blockade group [adjusted risk ratio = 0.66 (95% confidence interval 0.46 to 0.94)], and overall complications were comparable between groups. The health-economic analysis demonstrated that thoracic epidural blockade produced an additional 0.04 quality-adjusted life-years when compared to paravertebral blockade, and was associated with slightly lower costs, but these differences were not statistically significant.</p><p><strong>Limitations: </strong>The main limita
{"title":"The clinical and cost-effectiveness of paravertebral blockade versus thoracic epidural blockade in reducing chronic post-thoracotomy pain: TOPIC2 RCT synopsis.","authors":"Ben Shelley, Lee Middleton, Andreas Goebel, Stephen Grant, Louise Jackson, Mishal Javed, Marcus Jepson, Nandor Marczin, Rajnikant Mehta, Teresa Melody, Babu Naidu, Hannah Summers, Lajos Szentgyorgyi, Sarah Tearne, Ben Watkins, Matthew Wilson, Andrew Worrall, Joyce Yeung, Fang Gao Smith","doi":"10.3310/GJFG1715","DOIUrl":"https://doi.org/10.3310/GJFG1715","url":null,"abstract":"<p><strong>Background: </strong>More than a third of patients undergoing thoracotomy suffer from debilitating chronic post-thoracotomy pain lasting months or years postoperatively. Aggressive management of acute pain during the perioperative period may mitigate this risk.</p><p><strong>Objective(s): </strong>To determine the clinical and cost-effectiveness of paravertebral blockade compared to thoracic epidural blockade, by testing the hypothesis that paravertebral blockade reduces the incidence of chronic post-thoracotomy pain.</p><p><strong>Design and methods: </strong>A parallel, open, multicentre, randomised controlled with integrated health-economic evaluation and an internal pilot that incorporated a qualitative recruitment intervention.</p><p><strong>Setting and participants: </strong>Adult patients undergoing thoracotomy in 15 United Kingdom centres.</p><p><strong>Interventions: </strong>Paravertebral blockade compared to thoracic epidural blockade.</p><p><strong>Main outcome measures: </strong>The primary outcome was the presence of chronic post-thoracotomy pain at 6 months post randomisation defined as 'worst chest pain over the last week' of at least moderate intensity, with a visual analogue scale score ≥ 40 mm. Secondary outcomes included visual analogue scale pain scores in the acute (days 1, 2, 3 and discharge) and chronic (3, 6 and 12 months) phases postoperatively; Brief Pain Inventory; Short Form McGill Pain Questionnaire 2; Hospital Anxiety and Depression Scale; patient satisfaction; analgesia use in the acute and chronic phases; complications (analgesic, surgical and pulmonary) and mortality. For the economic evaluation, the EuroQol-5 Dimensions, five-level version questionnaire was utilised.</p><p><strong>Results: </strong>Between 8 January 2019 and 29 September 2023, 770 patients underwent randomisation; 33 did not proceed to thoracotomy. At 6 months, 59 (22%) of 272 participants in the paravertebral blockade group and 47 (16%) of 292 in the thoracic epidural blockade group developed chronic pain [adjusted risk ratio = 1.32 (95% confidence interval 0.93 to 1.86); adjusted risk difference = 0.05 (95% confidence interval -0.01 to 0.11); <i>p</i> = 0.12]. During the acute phase, both worst and average pain was higher on day 1 with paravertebral blockade [adjusted mean difference 7.7 mm (95% confidence interval 2.8 to 12.5) and 7.0 mm (95% confidence interval 2.7 to 11.2), respectively] but not different on days 2 and 3. Hypotension was less common in the paravertebral blockade group [adjusted risk ratio = 0.66 (95% confidence interval 0.46 to 0.94)], and overall complications were comparable between groups. The health-economic analysis demonstrated that thoracic epidural blockade produced an additional 0.04 quality-adjusted life-years when compared to paravertebral blockade, and was associated with slightly lower costs, but these differences were not statistically significant.</p><p><strong>Limitations: </strong>The main limita","PeriodicalId":12898,"journal":{"name":"Health technology assessment","volume":"30 16","pages":"1-21"},"PeriodicalIF":4.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146149640","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}
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