Citation: Trials. 2018, 19(1), 627
Author: van Miert C, Fernandes RM, Eccleson H, Bedson E, Lane S, Peak M, Thorburn K, Compton V, Woolfall K, Lacy D, Williamson P, McNamara PS
Abstract: BACKGROUND: Bronchiolitis is an acute lower respiratory infection which predominantly affects young children. Treatment for bronchiolitis is limited to supportive therapy. Nasal oxygen therapy is part of routine care, and delivery now incorporates varying levels of non-invasive continuous positive airway pressure and/or high-flow nasal cannula oxygen therapy. Despite wide clinical use, there remains a lack of evidence on the comparative effectiveness and safety of these interventions. Furthermore, research in this field is hampered by the use of multiple outcome measures in current clinical trials.
METHODS/DESIGN: This mixed methods study includes a systematic review of outcome measures, telephone interviews with parents, focus group workshops and a Delphi survey with healthcare professionals and parents. These methods will be used to identify and prioritise outcomes for inclusion in a core outcome set and to explore issues pertinent to the design of a future randomised controlled trial comparing different modes of oxygen therapy for bronchiolitis. UK hospitals will also be contacted and asked to complete a survey to provide an overview of current practice to enable assessment of capability and capacity to run a future clinical trial.
DISCUSSION: This study will facilitate the design of a future clinical trial of non-invasive ventilation in children with bronchiolitis which is acceptable to important stakeholders. Furthermore, core outcome set development will improve standardisation, measurement and reporting of clinically important outcomes in bronchiolitis.
TRIAL REGISTRATION: ISRCTN Registry, ISRCTN75766048. Registered on 18 December 2017. This study was retrospectively registered in the ISRCTN Registry and on the Core Outcome Measures in Effectiveness Trials (COMET) Initiative database (15 September 2017).
KEYWORDS: Bronchiolitis; Core outcome sets; High-flow nasal cannula; Nasal continuous positive airway pressure; Oxygen inhalation therapy
Link to PubMed record
Friday 16 November 2018
Tuesday 13 November 2018
WUTH publication: Concerns over Efficacy and Safety of 0.1% Cyclosporine a Cationic Emulsion in the Treatment of Severe Dry Eye Disease
Citation: European Journal of Ophthalmology. 2017, 27(6), e193
Author: Clearkin L
Abstract: Comment in: Author's Reply to: "Concerns Over: Efficacy and Safety of 0.1% Cyclosporine a Cationic Emulsion in the Treatment of Severe Dry Eye Disease". [Eur J Ophthalmol. 2017]
Comment on: Efficacy and safety of 0.1% cyclosporine A cationic emulsion in the treatment of severe dry eye disease: a multicenter randomized trial. [Eur J Ophthalmol. 2016]
Link to PubMed record
Author: Clearkin L
Abstract: Comment in: Author's Reply to: "Concerns Over: Efficacy and Safety of 0.1% Cyclosporine a Cationic Emulsion in the Treatment of Severe Dry Eye Disease". [Eur J Ophthalmol. 2017]
Comment on: Efficacy and safety of 0.1% cyclosporine A cationic emulsion in the treatment of severe dry eye disease: a multicenter randomized trial. [Eur J Ophthalmol. 2016]
Link to PubMed record
Wednesday 7 November 2018
WUTH publication: Legal, Regulatory and Ethical Frameworks or Standards for AI and Autonomous Robotic Surgery
Citation: The international journal of medical robotics and computer assisted surgery. 2018 Nov 5, e1968. [Epub ahead of print]
Author: O'Sullivan S, Nevejans N, Allen C, Blyth A, Leonard S, Pagallo U, Holzinger K, Holzinger A, Sajid MI, Ashrafian H
Abstract: BACKGROUND: This paper aims to move the debate forward regarding the potential of AI and autonomous robotic surgery with a particular focus on ethical and legal aspects.
METHODS: We conducted a literature search on current and emerging surgical robot technologies, relevant standards and legal systems worldwide. We provide a discussion of unique challenges for robotic surgery faced by proposals made for AI more generally (e.g. Explainable AI) as well as recommendations for developing/improving relevant standards or legal and regulatory frameworks.
CONCLUSION: We distinguished three types of robot responsibility by classifying responsibility into: I. Accountability; II. Liability and III. Culpability. The component which produces the least clarity is Culpability, since it is unthinkable in the current state of technology. We envision in the nearer future that, as with autonomous driving, a robot can learn routine tasks which can then be supervised by the surgeon (a doctor-in-the-loop) being in the driving seat.
Link to PubMed record
Author: O'Sullivan S, Nevejans N, Allen C, Blyth A, Leonard S, Pagallo U, Holzinger K, Holzinger A, Sajid MI, Ashrafian H
Abstract: BACKGROUND: This paper aims to move the debate forward regarding the potential of AI and autonomous robotic surgery with a particular focus on ethical and legal aspects.
METHODS: We conducted a literature search on current and emerging surgical robot technologies, relevant standards and legal systems worldwide. We provide a discussion of unique challenges for robotic surgery faced by proposals made for AI more generally (e.g. Explainable AI) as well as recommendations for developing/improving relevant standards or legal and regulatory frameworks.
CONCLUSION: We distinguished three types of robot responsibility by classifying responsibility into: I. Accountability; II. Liability and III. Culpability. The component which produces the least clarity is Culpability, since it is unthinkable in the current state of technology. We envision in the nearer future that, as with autonomous driving, a robot can learn routine tasks which can then be supervised by the surgeon (a doctor-in-the-loop) being in the driving seat.
Link to PubMed record
Friday 2 November 2018
WUTH publication: Adjunctive rifampicin to reduce early mortality from Staphylococcus aureus bacteraemia: the ARREST RCT
Citation: Health Technology Assessment. 2018, 22(59), 1-148
Author: Thwaites GE, Scarborough M, Szubert A, Saramago Goncalves P, Soares M, Bostock J, Nsutebu E, Tilley R, Cunningham R, Greig J, Wyllie SA, Wilson P, Auckland C, Cairns J, Ward D, Lal P, Guleri A, Jenkins N, Sutton J, Wiselka M, Armando GR, Graham C, Chadwick PR, Barlow G, Gordon NC, Young B, Meisner S, McWhinney P, Price DA, Harvey D, Nayar D, Jeyaratnam D, Planche T, Minton J, Hudson F, Hopkins S, Williams J, Török ME, Llewelyn MJ, Edgeworth JD, Walker AS
Abstract: BACKGROUND: Staphylococcus aureus bacteraemia is a common and frequently fatal infection. Adjunctive rifampicin may enhance early S. aureus killing, sterilise infected foci and blood faster, and thereby reduce the risk of dissemination, metastatic infection and death.
OBJECTIVES: To determine whether or not adjunctive rifampicin reduces bacteriological (microbiologically confirmed) failure/recurrence or death through 12 weeks from randomisation. Secondary objectives included evaluating the impact of rifampicin on all-cause mortality, clinically defined failure/recurrence or death, toxicity, resistance emergence, and duration of bacteraemia; and assessing the cost-effectiveness of rifampicin.
DESIGN: Parallel-group, randomised (1 : 1), blinded, placebo-controlled multicentre trial.
SETTING: UK NHS trust hospitals.
PARTICIPANTS: Adult inpatients (≥ 18 years) with meticillin-resistant or susceptible S. aureus grown from one or more blood cultures, who had received < 96 hours of antibiotic therapy for the current infection, and without contraindications to rifampicin.
INTERVENTIONS: Adjunctive rifampicin (600-900 mg/day, oral or intravenous) or placebo for 14 days in addition to standard antibiotic therapy. Investigators and patients were blinded to trial treatment. Follow-up was for 12 weeks (assessments at 3, 7, 10 and 14 days, weekly until discharge and final assessment at 12 weeks post randomisation).
MAIN OUTCOME MEASURES: The primary outcome was all-cause bacteriological (microbiologically confirmed) failure/recurrence or death through 12 weeks from randomisation.
RESULTS: Between December 2012 and October 2016, 758 eligible participants from 29 UK hospitals were randomised: 370 to rifampicin and 388 to placebo. The median age was 65 years [interquartile range (IQR) 50-76 years]. A total of 485 (64.0%) infections were community acquired and 132 (17.4%) were nosocomial; 47 (6.2%) were caused by meticillin-resistant S. aureus. A total of 301 (39.7%) participants had an initial deep infection focus. Standard antibiotics were given for a median of 29 days (IQR 18-45 days) and 619 (81.7%) participants received flucloxacillin. By 12 weeks, 62 out of 370 (16.8%) patients taking rifampicin versus 71 out of 388 (18.3%) participants taking the placebo experienced bacteriological (microbiologically confirmed) failure/recurrence or died [absolute risk difference -1.4%, 95% confidence interval (CI) -7.0% to 4.3%; hazard ratio 0.96, 95% CI 0.68 to 1.35; p = 0.81]. There were 4 (1.1%) and 5 (1.3%) bacteriological failures (p = 0.82) in the rifampicin and placebo groups, respectively. There were 3 (0.8%) versus 16 (4.1%) bacteriological recurrences (p = 0.01), and 55 (14.9%) versus 50 (12.9%) deaths without bacteriological failure/recurrence (p = 0.30) in the rifampicin and placebo groups, respectively. Over 12 weeks, there was no evidence of differences in clinically defined failure/recurrence/death (p = 0.84), all-cause mortality (p = 0.60), serious (p = 0.17) or grade 3/4 (p = 0.36) adverse events (AEs). However, 63 (17.0%) participants in the rifampicin group versus 39 (10.1%) participants in the placebo group experienced antibiotic or trial drug-modifying AEs (p = 0.004), and 24 (6.5%) participants in the rifampicin group versus 6 (1.5%) participants in the placebo group experienced drug-interactions (p = 0.0005). Evaluation of the costs and health-related quality-of-life impacts revealed that an episode of S. aureus bacteraemia costs an average of £12,197 over 12 weeks. Rifampicin was estimated to save 10% of episode costs (p = 0.14). After adjustment, the effect of rifampicin on total quality-adjusted life-years (QALYs) was positive (0.004 QALYs), but not statistically significant (standard error 0.004 QALYs).
CONCLUSIONS: Adjunctive rifampicin provided no overall benefit over standard antibiotic therapy in adults with S. aureus bacteraemia.
FUTURE WORK: Given the substantial mortality, other antibiotic combinations or improved source management should be investigated.
TRIAL REGISTRATIONS: Current Controlled Trials ISRCTN37666216, EudraCT 2012-000344-10 and Clinical Trials Authorisation 00316/0243/001.
FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 22, No. 59. See the NIHR Journals Library website for further project information.
Link to PubMed record
Author: Thwaites GE, Scarborough M, Szubert A, Saramago Goncalves P, Soares M, Bostock J, Nsutebu E, Tilley R, Cunningham R, Greig J, Wyllie SA, Wilson P, Auckland C, Cairns J, Ward D, Lal P, Guleri A, Jenkins N, Sutton J, Wiselka M, Armando GR, Graham C, Chadwick PR, Barlow G, Gordon NC, Young B, Meisner S, McWhinney P, Price DA, Harvey D, Nayar D, Jeyaratnam D, Planche T, Minton J, Hudson F, Hopkins S, Williams J, Török ME, Llewelyn MJ, Edgeworth JD, Walker AS
Abstract: BACKGROUND: Staphylococcus aureus bacteraemia is a common and frequently fatal infection. Adjunctive rifampicin may enhance early S. aureus killing, sterilise infected foci and blood faster, and thereby reduce the risk of dissemination, metastatic infection and death.
OBJECTIVES: To determine whether or not adjunctive rifampicin reduces bacteriological (microbiologically confirmed) failure/recurrence or death through 12 weeks from randomisation. Secondary objectives included evaluating the impact of rifampicin on all-cause mortality, clinically defined failure/recurrence or death, toxicity, resistance emergence, and duration of bacteraemia; and assessing the cost-effectiveness of rifampicin.
DESIGN: Parallel-group, randomised (1 : 1), blinded, placebo-controlled multicentre trial.
SETTING: UK NHS trust hospitals.
PARTICIPANTS: Adult inpatients (≥ 18 years) with meticillin-resistant or susceptible S. aureus grown from one or more blood cultures, who had received < 96 hours of antibiotic therapy for the current infection, and without contraindications to rifampicin.
INTERVENTIONS: Adjunctive rifampicin (600-900 mg/day, oral or intravenous) or placebo for 14 days in addition to standard antibiotic therapy. Investigators and patients were blinded to trial treatment. Follow-up was for 12 weeks (assessments at 3, 7, 10 and 14 days, weekly until discharge and final assessment at 12 weeks post randomisation).
MAIN OUTCOME MEASURES: The primary outcome was all-cause bacteriological (microbiologically confirmed) failure/recurrence or death through 12 weeks from randomisation.
RESULTS: Between December 2012 and October 2016, 758 eligible participants from 29 UK hospitals were randomised: 370 to rifampicin and 388 to placebo. The median age was 65 years [interquartile range (IQR) 50-76 years]. A total of 485 (64.0%) infections were community acquired and 132 (17.4%) were nosocomial; 47 (6.2%) were caused by meticillin-resistant S. aureus. A total of 301 (39.7%) participants had an initial deep infection focus. Standard antibiotics were given for a median of 29 days (IQR 18-45 days) and 619 (81.7%) participants received flucloxacillin. By 12 weeks, 62 out of 370 (16.8%) patients taking rifampicin versus 71 out of 388 (18.3%) participants taking the placebo experienced bacteriological (microbiologically confirmed) failure/recurrence or died [absolute risk difference -1.4%, 95% confidence interval (CI) -7.0% to 4.3%; hazard ratio 0.96, 95% CI 0.68 to 1.35; p = 0.81]. There were 4 (1.1%) and 5 (1.3%) bacteriological failures (p = 0.82) in the rifampicin and placebo groups, respectively. There were 3 (0.8%) versus 16 (4.1%) bacteriological recurrences (p = 0.01), and 55 (14.9%) versus 50 (12.9%) deaths without bacteriological failure/recurrence (p = 0.30) in the rifampicin and placebo groups, respectively. Over 12 weeks, there was no evidence of differences in clinically defined failure/recurrence/death (p = 0.84), all-cause mortality (p = 0.60), serious (p = 0.17) or grade 3/4 (p = 0.36) adverse events (AEs). However, 63 (17.0%) participants in the rifampicin group versus 39 (10.1%) participants in the placebo group experienced antibiotic or trial drug-modifying AEs (p = 0.004), and 24 (6.5%) participants in the rifampicin group versus 6 (1.5%) participants in the placebo group experienced drug-interactions (p = 0.0005). Evaluation of the costs and health-related quality-of-life impacts revealed that an episode of S. aureus bacteraemia costs an average of £12,197 over 12 weeks. Rifampicin was estimated to save 10% of episode costs (p = 0.14). After adjustment, the effect of rifampicin on total quality-adjusted life-years (QALYs) was positive (0.004 QALYs), but not statistically significant (standard error 0.004 QALYs).
CONCLUSIONS: Adjunctive rifampicin provided no overall benefit over standard antibiotic therapy in adults with S. aureus bacteraemia.
FUTURE WORK: Given the substantial mortality, other antibiotic combinations or improved source management should be investigated.
TRIAL REGISTRATIONS: Current Controlled Trials ISRCTN37666216, EudraCT 2012-000344-10 and Clinical Trials Authorisation 00316/0243/001.
FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 22, No. 59. See the NIHR Journals Library website for further project information.
Link to PubMed record
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