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Background: Pathologic confirmation of lung cancer influences treatment selection for suspected early-stage lung cancer. High pre-treatment tissue confirmation rates are recommended. We sought to define management and outcomes of patients undergoing surgery for primary lung cancer in a UK multi-centre clinical trial., Methods: VIOLET compared minimally invasive video-assisted thoracic surgery versus open surgery for known or suspected lung cancer. Diagnostic patient pathways were identified and methods of tissue confirmation were documented. The outcome of inappropriate lobectomy for benign disease or inappropriate wedge resection for primary lung cancer was compared with respect to the pathologic diagnosis., Findings: From July 2015 to February 2019, 502 patients were randomised and underwent surgery; 262 (52%) had a pre-operative pathologic confirmed diagnosis of primary lung cancer, 205 did not have a pre-operative biopsy and 35 had a non-diagnostic pre-operative biopsy. Of the 240 participants without pre-operative pathologic confirmation of primary lung cancer, intraoperative biopsy and frozen section analysis was undertaken in 144 (60%). The remaining 96 underwent direct surgical resection without tissue confirmation (19% of the entire cohort). Confirmation of histologic diagnosis before surgery was less costly than diagnosis in the operating theatre. The inappropriate surgery rate was 3.6% (18/502 participants, 7 lobectomy for benign disease, 11 wedge resection for lung cancer)., Interpretation: Low levels of inappropriate resection can be achieved at pre-operative tissue confirmation rates of 50% through a combination of intra-operative confirmatory biopsy and correct risk estimation of lung cancer. Practice needs to be monitored to ensure acceptable levels are consistently achieved., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Eric Lim reports personal fees from Abbott Molecular (Abbott Park, IL, USA), GlaxoSmithKline plc (Brentford, UK), Pfizer Inc. (New York, NY, USA), Novartis Pharmaceuticals UK Ltd (London, UK), Medtronic plc/Covidien (Dublin, Ireland), Roche Diagnostics (Hertford, UK), Lilly Oncology (Indianapolis, IN, USA), Boehringer Ingelheim (Bracknell, UK), Medela (Baar, Switzerland), Johnson & Johnson/Ethicon (New Brunswick, NJ, USA), AstraZeneca (Cambridge, UK) and Bristol-Myers Squibb (New York, NY, USA); grants from Clearbridge BioMedics (Singapore Science Park, Singapore), Illumina (San Diego, CA, USA) and Guardant Health (Redwood City, CA, USA); and grants and personal fees from ScreenCell (Sarcelles, France) outside the submitted work. In addition, Eric Lim has patents P52435GB and P57988GB issued to Imperial Innovations (London, UK). Timothy Batchelor reports personal fees from Johnson & Johnson, Medtronic plc, Medela and AstraZeneca outside the submitted work., (Copyright © 2025 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Lung cancer is the most common cause of cancer death worldwide and most patients present with extensive disease. One-year survival is improving but remains low (37%) despite novel systemic anti-cancer treatments forming the current standard of care. Although new therapies improve survival, most patients have residual disease after treatment, and little is known on how best to manage it. Therefore, residual disease management varies across the UK, with some patients receiving only maintenance systemic anti-cancer treatment while others receive local consolidative treatment (LCT), alongside maintenance systemic anti-cancer treatment. LCT can be a combination of surgery, radiotherapy and/or ablation to remove all remaining cancer within the lung and throughout the body. This is intensive, expensive and impacts quality of life, but we do not know if it results in better survival, nor the extent of impact on quality of life and what the cost might be for healthcare providers. The RAMON study (RAdical Management Of Advanced Non-small cell lung cancer) will evaluate the acceptability, effectiveness and cost-effectiveness of LCT versus no LCT after first-line systemic treatment for advanced lung cancer., Methods and Analysis: RAMON is a pragmatic open multicentre, parallel group, superiority randomised controlled trial. We aim to recruit 244 patients aged 18 years and over with advanced non-small-cell lung cancer from 40 UK NHS hospitals. Participants will be randomised in a 1:1 ratio to receive LCT alongside maintenance treatment, or maintenance treatment alone. LCT will be tailored to each patient's specific disease sites. Participants will be followed up for a minimum of 2 years. The primary outcome is overall survival from randomisation., Ethics and Dissemination: The West of Scotland Research Ethics Committee (22/WS/0121) gave ethical approval in August 2022 and the Health Research Authority in September 2022. Participants will provide written informed consent before participating in the study. Findings will be presented at international meetings, in peer-reviewed publications, through patient organisations and notifications to patients., Trial Registration Number: ISRCTN11613852., Competing Interests: Competing interests: All authors received support from the National Institute for Health and Care Research for the project associated with this manuscript, which was paid to their employing institution. EL reports personal fees from Abbott Molecular, AstraZeneca, Glaxo Smith Kline, Pfizer, Norvatis, Covidien, Roche, Lily Oncology, Boehringer Ingelheim, Medela, Ethicon, and AstraZeneca, and grants from ScreenCell, Clearbridge Biomedics, Illumina, and Guardant Health. PDS reports personal fees from Vitae Professionals. JR reports personal and travel fees from NCRI Lung Advanced disease subgroup, ELF lung cancer patient advisory group, BTOG, Clinical expert group lung cancer, WM Cancer Alliance lung cancer and mesothelioma EAG (as a patient representative). TND reports personal fees from AstraZenca, BMS, Boehringer Ingelheim, Lilly, MSD, Otsuka, Roche, Takeda, BMS, Eli-Lilly, Novartis, and Pfizer., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Insomnia is common, and difficulty with daytime functioning is a core symptom. Studies show cognitive behavioural therapy (CBT) improves functioning, but evidence is needed on its value for money. Quality-adjusted life years (QALYs), capturing length and quality of life, provide a standard metric by which to judge whether a treatment is worth its cost. Studies have found QALY gains with therapist-delivered and therapist-guided CBT, but most have not reached statistical significance. Estimates of QALY gains with fully automated digital CBT (dCBT) for insomnia are lacking., Aim: To assess whether dCBT (Sleepio) for insomnia is associated with gains in QALYs compared with a sleep hygiene education control., Design & Setting: A secondary analysis of a large effectiveness trial of 1711 participants from the UK, US, and Australia., Method: EQ-5D scores, the National Institute for Health and Care Excellence's (NICE's) preferred measure of health-related quality of life (HRQoL), were predicted (mapped) from the 10-item Patient-Reported Outcomes Measurement Information System (PROMIS-10) Global Health scores and used to determine QALYs from baseline to 24 weeks (controlled), and to 48 weeks (uncontrolled)., Results: At week 24, QALYs were significantly higher for the dCBT group, with mean QALYs 0.375 and 0.362 in the dCBT and control groups, respectively. The mean difference was 0.014 (95% confidence interval [CI] = 0.008 to 0.019), and this difference was maintained over the 48-week study period (0.026, 95% CI = 0.016 to 0.036). The difference of 0.026 QALYs is equivalent to 9.5 days in perfect health., Conclusion: Sleepio is associated with statistically significant gains in QALYs over time compared with control. Findings may be used to power future studies and inform cost-effectiveness analyses of automated dCBT for insomnia scaled to a population level., (Copyright © 2022, The Authors.)

Background: Lung cancer is the leading cause of cancer death. Surgery remains the main method of managing early-stage disease. Minimal-access video-assisted thoracoscopic surgery results in less tissue trauma than open surgery; however, it is not known if it improves patient outcomes., Objective: To compare the clinical effectiveness and cost-effectiveness of video-assisted thoracoscopic surgery lobectomy with open surgery for the treatment of lung cancer., Design, Setting and Participants: A multicentre, superiority, parallel-group, randomised controlled trial with blinding of participants (until hospital discharge) and outcome assessors conducted in nine NHS hospitals. Adults referred for lung resection for known or suspected lung cancer, with disease suitable for both surgeries, were eligible. Participants were followed up for 1 year., Interventions: Participants were randomised 1 : 1 to video-assisted thoracoscopic surgery lobectomy or open surgery. Video-assisted thoracoscopic surgery used one to four keyhole incisions without rib spreading. Open surgery used a single incision with rib spreading, with or without rib resection., Main Outcome Measures: The primary outcome was self-reported physical function (using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30) at 5 weeks. Secondary outcomes included upstaging to pathologic node stage 2 disease, time from surgery to hospital discharge, pain in the first 2 days, prolonged pain requiring analgesia at > 5 weeks, adverse health events, uptake of adjuvant treatment, overall and disease-free survival, quality of life (Quality of Life Questionnaire Core 30, Quality of Life Questionnaire Lung Cancer 13 and EQ-5D) at 2 and 5 weeks and 3, 6 and 12 months, and cost-effectiveness., Results: A total of 503 patients were randomised between July 2015 and February 2019 (video-assisted thoracoscopic surgery, n  = 247; open surgery, n  = 256). One participant withdrew before surgery. The mean age of patients was 69 years; 249 (49.5%) patients were men and 242 (48.1%) did not have a confirmed diagnosis. Lobectomy was performed in 453 of 502 (90.2%) participants and complete resection was achieved in 429 of 439 (97.7%) participants. Quality of Life Questionnaire Core 30 physical function was better in the video-assisted thoracoscopic surgery group than in the open-surgery group at 5 weeks (video-assisted thoracoscopic surgery, n  = 247; open surgery, n  = 255; mean difference 4.65, 95% confidence interval 1.69 to 7.61; p  = 0.0089). Upstaging from clinical node stage 0 to pathologic node stage 1 and from clinical node stage 0 or 1 to pathologic node stage 2 was similar ( p  ≥ 0.50). Pain scores were similar on day 1, but lower in the video-assisted thoracoscopic surgery group on day 2 (mean difference -0.54, 95% confidence interval -0.99 to -0.09; p  = 0.018). Analgesic consumption was 10% lower (95% CI -20% to 1%) and the median hospital stay was less (4 vs. 5 days, hazard ratio 1.34, 95% confidence interval 1.09, 1.65; p  = 0.006) in the video-assisted thoracoscopic surgery group than in the open-surgery group. Prolonged pain was also less (relative risk 0.82, 95% confidence interval 0.72 to 0.94; p  = 0.003). Time to uptake of adjuvant treatment, overall survival and progression-free survival were similar ( p  ≥ 0.28). Fewer participants in the video-assisted thoracoscopic surgery group than in the open-surgery group experienced complications before and after discharge from hospital (relative risk 0.74, 95% confidence interval 0.66 to 0.84; p  < 0.001 and relative risk 0.81, 95% confidence interval 0.66 to 1.00; p  = 0.053, respectively). Quality of life to 1 year was better across several domains in the video-assisted thoracoscopic surgery group than in the open-surgery group. The probability that video-assisted thoracoscopic surgery is cost-effective at a willingness-to-pay threshold of £20,000 per quality-adjusted life-year is 1., Limitations: Ethnic minorities were under-represented compared with the UK population (< 5%), but the cohort reflected the lung cancer population., Conclusions: Video-assisted thoracoscopic surgery lobectomy was associated with less pain, fewer complications and better quality of life without any compromise to oncologic outcome. Use of video-assisted thoracoscopic surgery is highly likely to be cost-effective for the NHS., Future Work: Evaluation of the efficacy of video-assisted thoracoscopic surgery with robotic assistance, which is being offered in many hospitals., Trial Registration: This trial is registered as ISRCTN13472721., Funding: This project was funded by the National Institute for Health and Care Research ( NIHR ) Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 26, No. 48. See the NIHR Journals Library website for further project information.

Background: When a cardiac arrest occurs, cardiopulmonary resuscitation should be started immediately. However, there is limited evidence about the best approach to airway management during cardiac arrest., Objective: The objective was to determine whether or not the i-gel ® (Intersurgical Ltd, Wokingham, UK) supraglottic airway is superior to tracheal intubation as the initial advanced airway management strategy in adults with non-traumatic out-of-hospital cardiac arrest., Design: This was a pragmatic, open, parallel, two-group, multicentre, cluster randomised controlled trial. A cost-effectiveness analysis accompanied the trial., Setting: The setting was four ambulance services in England., Participants: Patients aged ≥ 18 years who had a non-traumatic out-of-hospital cardiac arrest and were attended by a participating paramedic were enrolled automatically under a waiver of consent between June 2015 and August 2017. Follow-up ended in February 2018., Intervention: Paramedics were randomised 1 : 1 to use tracheal intubation (764 paramedics) or i-gel (759 paramedics) for their initial advanced airway management and were unblinded., Main Outcome Measures: The primary outcome was modified Rankin Scale score at hospital discharge or 30 days after out-of-hospital cardiac arrest, whichever occurred earlier, collected by assessors blinded to allocation. The modified Rankin Scale, a measure of neurological disability, was dichotomised: a score of 0-3 (good outcome) or 4-6 (poor outcome/death). The primary outcome for the economic evaluation was quality-adjusted life-years, estimated using the EuroQol-5 Dimensions, five-level version., Results: A total of 9296 patients (supraglottic airway group, 4886; tracheal intubation group, 4410) were enrolled [median age 73 years; 3373 (36.3%) women]; modified Rankin Scale score was known for 9289 patients. Characteristics were similar between groups. A total of 6.4% (311/4882) of patients in the supraglottic airway group and 6.8% (300/4407) of patients in the tracheal intubation group had a good outcome (adjusted difference in proportions of patients experiencing a good outcome: -0.6%, 95% confidence interval -1.6% to 0.4%). The supraglottic airway group had a higher initial ventilation success rate than the tracheal intubation group [87.4% (4255/4868) vs. 79.0% (3473/4397), respectively; adjusted difference in proportions of patients: 8.3%, 95% confidence interval 6.3% to 10.2%]; however, patients in the tracheal intubation group were less likely to receive advanced airway management than patients in the supraglottic airway group [77.6% (3419/4404) vs. 85.2% (4161/4883), respectively]. Regurgitation rate was similar between the groups [supraglottic airway group, 26.1% (1268/4865); tracheal intubation group, 24.5% (1072/4372); adjusted difference in proportions of patients: 1.4%, 95% confidence interval -0.6% to 3.4%], as was aspiration rate [supraglottic airway group, 15.1% (729/4824); tracheal intubation group, 14.9% (647/4337); adjusted difference in proportions of patients: 0.1%, 95% confidence interval -1.5% to 1.8%]. The longer-term outcomes were also similar between the groups (modified Rankin Scale: at 3 months, odds ratio 0.89, 95% confidence interval 0.69 to 1.14; at 6 months, odds ratio 0.91, 95% confidence interval 0.71 to 1.16). Sensitivity analyses did not alter the overall findings. There were no unexpected serious adverse events. Mean quality-adjusted life-years to 6 months were 0.03 in both groups (supraglottic airway group minus tracheal intubation group difference -0.0015, 95% confidence interval -0.0059 to 0.0028), and total costs were £157 (95% confidence interval -£270 to £583) lower in the tracheal intubation group. Although the point estimate of the incremental cost-effectiveness ratio suggested that tracheal intubation may be cost-effective, the huge uncertainty around this result indicates no evidence of a difference between groups., Limitations: Limitations included imbalance in the number of patients in each group, caused by unequal distribution of high-enrolling paramedics; crossover between groups; and the fact that participating paramedics, who were volunteers, might not be representative of all paramedics in the UK. Findings may not be applicable to other countries., Conclusion: Among patients with out-of-hospital cardiac arrest, randomisation to the supraglottic airway group compared with the tracheal intubation group did not result in a difference in outcome at 30 days. There were no notable differences in costs, outcomes and overall cost-effectiveness between the groups., Future Work: Future work could compare alternative supraglottic airway types with tracheal intubation; include a randomised trial of bag mask ventilation versus supraglottic airways; and involve other patient populations, including children, people with trauma and people in hospital., Trial Registration: This trial is registered as ISRCTN08256118., Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and supported by the NIHR Comprehensive Research Networks and will be published in full in Health Technology Assessment ; Vol. 26, No. 21. See the NIHR Journals Library website for further project information.

BACKGROUND: There is limited randomized evidence on the comparative outcomes of early-stage lung cancer resection by video-assisted thoracoscopic surgery (VATS) versus open resection. METHODS: We conducted a parallel-group multicenter randomized trial that recruited participants with known or suspected early-stage lung cancer and randomly assigned them to open or VATS resection of their lesions. The primary outcome was physical function at 5 weeks as a measure of recovery using the European Organisation for Research and Treatment of Cancer core health-related quality of life questionnaire (QLQ-C30) (scores range from 0 to 100, with higher scores indicating better function; the clinical minimally important difference for improvement is 5 points). We followed the patients for an additional 47 weeks for other outcomes. RESULTS: A total of 503 participants were randomly assigned (247 to VATS and 256 to open lobectomy). At 5 weeks, median physical function was 73 in the VATS group and 67 in the open surgery group, with a mean difference of 4.65 points (95% confidence interval, 1.69 to 7.61). Of the participants allocated to VATS, 30.7% had serious adverse events after discharge compared with 37.8% of those allocated to open surgery (risk ratio, 0.81 [95% confidence interval, 0.66 to 1.00]). At 52 weeks, there were no differences in cancer progression-free survival (hazard ratio, 0.74 [0.43 to 1.27]) or overall survival (hazard ratio, 0.67 [0.32 to 1.40]). CONCLUSIONS: VATS lobectomy for lung cancer is associated with a better recovery of physical function in the 5 weeks after random assignment compared with open surgery. Long-term oncologic outcomes will require continued follow-up to assess. (Funded by the National Institute for Health Research Health Technology Assessment programme [reference number 13/04/03]; ISRCTN number, ISRCTN13472721.)

Aim: Optimal airway management during out-of-hospital cardiac arrest (OHCA) is uncertain. Complications from tracheal intubation (TI) may be avoided with supraglottic airway (SGA) devices. The AIRWAYS-2 cluster randomised controlled trial (ISRCTN08256118) compared the i-gel SGA with TI as the initial advanced airway management (AAM) strategy by paramedics treating adults with non-traumatic OHCA. This paper reports the trial cost-effectiveness analysis., Methods: A within-trial cost-effectiveness analysis of the i-gel compared with TI was conducted, with a six-month time horizon, from the perspective of the UK National Health Service (NHS) and personal social services. The primary outcome measure was quality-adjusted life years (QALYs), estimated using the EQ-5D-5L questionnaire. Multilevel linear regression modelling was used to account for clustering by paramedic when combining costs and outcomes., Results: 9296 eligible patients were attended by 1382 trial paramedics and enrolled in the AIRWAYS-2 trial (4410 TI, 4886 i-gel). Mean QALYs to six months were 0.03 in both groups (i-gel minus TI difference -0.0015, 95% CI -0.0059 to 0.0028). Total costs per participant up to six months post-OHCA were £3570 and £3413 in the i-gel and TI groups respectively (mean difference £157, 95% CI -£270 to £583). Based on mean difference point estimates, TI was more effective and less costly than i-gel; however differences were small and there was great uncertainty around these results., Conclusion: The small differences between groups in QALYs and costs shows no difference in the cost-effectiveness of the i-gel and TI when used as the initial AAM strategy in adults with non-traumatic OHCA., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Gabapentin is an antiepileptic drug currently licensed to treat epilepsy and neuropathic pain but has been used off-label to treat acute postoperative pain. The GAP study will compare the effectiveness, cost-effectiveness and safety of gabapentin as an adjunct to standard multimodal analgesia versus placebo for the management of pain after major surgery., Methods and Analysis: The GAP study is a multicentre, double-blind, randomised controlled trial in patients aged 18 years and over, undergoing different types of major surgery (cardiac, thoracic or abdominal). Patients will be randomised in a 1:1 ratio to receive either gabapentin (600 mg just before surgery and 600 mg/day for 2 days after surgery) or placebo in addition to usual pain management for each type of surgery. Patients will be followed up daily until hospital discharge and then at 4 weeks and 4 months after surgery. The primary outcome is length of hospital stay following surgery. Secondary outcomes include pain, total opioid use, adverse health events, health related quality of life and costs., Ethics and Dissemination: This study has been approved by the Research Ethics Committee . Findings will be shared with participating hospitals and disseminated to the academic community through peer-reviewed publications and presentation at national and international meetings. Patients will be informed of the results through patient organisations and participant newsletters., Trial Registration Number: ISRCTN63614165., Competing Interests: Competing interests: No competing interests are declared. At the time that the work was carried out, GC was employed by the University Hospitals Bristol NHS Foundation Trust, Bristol, UK. GC is currently the Medical Director Johnson and Johnson Medical Devices UK and Ireland. GC has no competing interests to declare., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

Introduction: Mesothelioma remains a lethal cancer. To date, systemic therapy with pemetrexed and a platinum drug remains the only licensed standard of care. As the median survival for patients with mesothelioma is 12.1 months, surgery is an important consideration to improve survival and/or quality of life. Currently, only two surgical trials have been performed which found that neither extensive (extra-pleural pneumonectomy) or limited (partial pleurectomy) surgery improved survival (although there was some evidence of improved quality of life). Therefore, clinicians are now looking to evaluate pleurectomy decortication, the only radical treatment option left., Methods and Analysis: The MARS 2 study is a UK multicentre open parallel group randomised controlled trial comparing the effectiveness and cost-effectiveness of surgery-(extended) pleurectomy decortication-versus no surgery for the treatment of pleural mesothelioma. The study will test the hypothesis that surgery and chemotherapy is superior to chemotherapy alone with respect to overall survival. Secondary outcomes include health-related quality of life, progression-free survival, measures of safety (adverse events) and resource use to 2 years. The QuinteT Recruitment Intervention is integrated into the trial to optimise recruitment., Ethics and Dissemination: Research ethics approval was granted by London - Camberwell St. Giles Research Ethics Committee (reference 13/LO/1481) on 7 November 2013. We will submit the results for publication in a peer-reviewed journal., Trial Registration Numbers: ISRCTN-ISRCTN44351742 and ClinicalTrials.gov-NCT02040272., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

Introduction: Lung cancer is a leading cause of cancer deaths worldwide and surgery remains the main treatment for early stage disease. Prior to the introduction of video-assisted thoracoscopic surgery (VATS), lung resection for cancer was undertaken through an open thoracotomy. To date, the evidence base supporting the different surgical approaches is based on non-randomised studies, small randomised trials and is focused mainly on short-term in-hospital outcomes., Methods and Analysis: The VIdeo assisted thoracoscopic lobectomy versus conventional Open LobEcTomy for lung cancer study is a UK multicentre parallel group randomised controlled trial (RCT) with blinding of outcome assessors and participants (to hospital discharge) comparing the effectiveness, cost-effectiveness and acceptability of VATS lobectomy versus open lobectomy for treatment of lung cancer. We will test the hypothesis that VATS lobectomy is superior to open lobectomy with respect to self-reported physical function 5 weeks after randomisation (approximately 1 month after surgery). Secondary outcomes include assessment of efficacy (hospital stay, pain, proportion and time to uptake of chemotherapy), measures of safety (adverse health events), oncological outcomes (proportion of patients upstaged to pathologic N2 (pN2) disease and disease-free survival), overall survival and health related quality of life to 1 year. The QuinteT Recruitment Intervention is integrated into the trial to optimise recruitment., Ethics and Dissemination: This trial has been approved by the UK (Dulwich) National Research Ethics Service Committee London. Findings will be written-up as methodology papers for conference presentation, and publication in peer-reviewed journals. Many aspects of the feasibility work will inform surgical RCTs in general and these will be reported at methodology meetings. We will also link with lung cancer clinical studies groups. The patient and public involvement group that works with the Respiratory Biomedical Research Unit at the Brompton Hospital will help identify how we can best publicise the findings., Trial Registration Number: ISRCTN13472721., Competing Interests: Competing interests: Prof. Rogers reports grants from British Heart Foundation, during the conduct of the study;Dr. Dunning reports personal fees from Cambridge Medical Robotics, personal fees from LIVSMed, outside the submitted work;Dr. Stokes reports grants from UK National Institute for Health Research (Health Technology Assessment Programme), Department of Health and Social Care, during the conduct of the study;Prof. Wordsworth reports grants from UK National Institute for Health Research (Health Technology Assessment Programme), Department of Health and Social Care, during the conduct of the study;Prof. Lim reports personal fees from Abbott Molecular, personal fees from Glaxo Smith Kline, personal fees from Pfizer, personal fees from Norvatis, personal fees from Covidien, personal fees from Roche, personal fees from Lily Oncology, personal fees from Boehringer Ingelheim, personal fees from Medela, grants and personal fees from ScreenCell, personal fees from Ethicon, grants from Clearbridge Biomedics, grants from Guardant Health, outside the submitted work;Dr. Paramasivan reports grants from National Institute for Health Research (NIHR), during the conduct of the study;Dr. Batchelor reports personal fees from Medtronic, personal fees from Johnson & Johnson, personal fees from PulmonX, personal fees from AstraZeneca, outside the submitted work;Miss. Mckeon, Dr. McGonigle, Miss. Harris, Dr. Shackcloth, Dr. Elliot, Prof. Blazeby, Ms. Dabner, Mr. Brush have nothing to disclose, (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.)

Objective: To identify the key drivers of cost-effectiveness for cardiovascular magnetic resonance (CMR) when patients activate the primary percutaneous coronary intervention (PPCI) pathway., Design: Economic decision models for two patient subgroups populated from secondary sources, each with a 1 year time horizon from the perspective of the National Health Service (NHS) and personal social services in the UK., Setting: Usual care (with or without CMR) in the NHS., Participants: Patients who activated the PPCI pathway, and for Model 1: underwent an emergency coronary angiogram and PPCI, and were found to have multivessel coronary artery disease. For Model 2: underwent an emergency coronary angiogram and were found to have unobstructed coronary arteries., Interventions: Model 1 (multivessel disease) compared two different ischaemia testing methods, CMR or fractional flow reserve (FFR), versus stress echocardiography. Model 2 (unobstructed arteries) compared CMR with standard echocardiography versus standard echocardiography alone., Main Outcome Measures: Key drivers of cost-effectiveness for CMR, incremental costs and quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios., Results: In both models, the incremental costs and QALYs between CMR (or FFR, Model 1) versus no CMR (stress echocardiography, Model 1 and standard echocardiography, Model 2) were small (CMR: -£64 (95% CI -£232 to £187)/FFR: £360 (95% CI -£116 to £844) and CMR/FFR: 0.0012 QALYs (95% CI -0.0076 to 0.0093)) and (£98 (95% CI -£199 to £488) and 0.0005 QALYs (95% CI -0.0050 to 0.0077)), respectively. The diagnostic accuracy of the tests was the key driver of cost-effectiveness for both patient groups., Conclusions: If CMR were introduced for all subgroups of patients who activate the PPCI pathway, it is likely that diagnostic accuracy would be a key determinant of its cost-effectiveness. Further research is needed to definitively answer whether revascularisation guided by CMR or FFR leads to different clinical outcomes in acute coronary syndrome patients with multivessel disease., Competing Interests: Competing interests: Chiara Bucciarelli-Ducci has received personal fees from Circle Cardiovascular Imaging. Barnaby C Reeves reports former membership of the Health Technology Assessment Commissioning Board (up to 31 March 2016) and Health Technology Assessment Efficient Study Designs Board (October 2014 to December 2014). He also reports current membership of the Health Technology Assessment IP Methods Group and Systematic Reviews Programme Advisory Group (Systematic Reviews NIHR Cochrane Incentive Awards and Systematic Review Advisory Group). Beyond this, all authors have no competing interests, except support from the NIHR grant as detailed in the funding statement., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.)

Importance: The optimal approach to airway management during out-of-hospital cardiac arrest is unknown., Objective: To determine whether a supraglottic airway device (SGA) is superior to tracheal intubation (TI) as the initial advanced airway management strategy in adults with nontraumatic out-of-hospital cardiac arrest., Design, Setting, and Participants: Multicenter, cluster randomized clinical trial of paramedics from 4 ambulance services in England responding to emergencies for approximately 21 million people. Patients aged 18 years or older who had a nontraumatic out-of-hospital cardiac arrest and were treated by a participating paramedic were enrolled automatically under a waiver of consent between June 2015 and August 2017; follow-up ended in February 2018., Interventions: Paramedics were randomized 1:1 to use TI (764 paramedics) or SGA (759 paramedics) as their initial advanced airway management strategy., Main Outcomes and Measures: The primary outcome was modified Rankin Scale score at hospital discharge or 30 days after out-of-hospital cardiac arrest, whichever occurred sooner. Modified Rankin Scale score was divided into 2 ranges: 0-3 (good outcome) or 4-6 (poor outcome; 6 = death). Secondary outcomes included ventilation success, regurgitation, and aspiration., Results: A total of 9296 patients (4886 in the SGA group and 4410 in the TI group) were enrolled (median age, 73 years; 3373 were women [36.3%]), and the modified Rankin Scale score was known for 9289 patients. In the SGA group, 311 of 4882 patients (6.4%) had a good outcome (modified Rankin Scale score range, 0-3) vs 300 of 4407 patients (6.8%) in the TI group (adjusted risk difference [RD], -0.6% [95% CI, -1.6% to 0.4%]). Initial ventilation was successful in 4255 of 4868 patients (87.4%) in the SGA group compared with 3473 of 4397 patients (79.0%) in the TI group (adjusted RD, 8.3% [95% CI, 6.3% to 10.2%]). However, patients randomized to receive TI were less likely to receive advanced airway management (3419 of 4404 patients [77.6%] vs 4161 of 4883 patients [85.2%] in the SGA group). Two of the secondary outcomes (regurgitation and aspiration) were not significantly different between groups (regurgitation: 1268 of 4865 patients [26.1%] in the SGA group vs 1072 of 4372 patients [24.5%] in the TI group; adjusted RD, 1.4% [95% CI, -0.6% to 3.4%]; aspiration: 729 of 4824 patients [15.1%] vs 647 of 4337 patients [14.9%], respectively; adjusted RD, 0.1% [95% CI, -1.5% to 1.8%])., Conclusions and Relevance: Among patients with out-of-hospital cardiac arrest, randomization to a strategy of advanced airway management with a supraglottic airway device compared with tracheal intubation did not result in a favorable functional outcome at 30 days., Trial Registration: ISRCTN Identifier: 08256118.

Background: In an environment of limited health care resources, it is crucial for health care systems which provide blood transfusion to have accurate and comprehensive information on the costs of transfusion, incorporating not only the costs of blood products, but also their administration. Unfortunately, in many countries accurate costs for administering blood are not available. Our study aimed to generate comprehensive estimates of the costs of administering transfusions for the UK National Health Service., Study Design and Methods: A detailed microcosting study was used to cost two key inputs into transfusion: transfusion laboratory and nursing inputs. For each input, data collection forms were developed to capture staff time, equipment, and consumables associated with each step in the transfusion process. Costing results were combined with costs of blood product wastage to calculate the cost per unit transfused, separately for different blood products. Data were collected in 2014/15 British pounds and converted to US dollars., Results: A total of 438 data collection forms were completed by 74 staff. The cost of administering blood was $71 (£49) per unit for red blood cells, $84 (£58) for platelets, $55 (£38) for fresh-frozen plasma, and $72 (£49) for cryoprecipitate., Conclusions: Blood administration costs add substantially to the costs of the blood products themselves. These are frequently incurred costs; applying estimates to the blood components supplied to UK hospitals in 2015, the annual cost of blood administration, excluding blood products, exceeds $175 (£120) million. These results provide more accurate estimates of the total costs of transfusion than those previously available., (© 2018 AABB.)

Background: We assessed whether a near-infrared spectroscopy (NIRS)-based algorithm for the personalized optimization of cerebral oxygenation during cardiopulmonary bypass combined with a restrictive red cell transfusion threshold would reduce perioperative injury to the brain, heart, and kidneys., Methods: In a randomized controlled trial, participants in three UK centres were randomized with concealed allocation to a NIRS (INVOS 5100; Medtronic Inc., Minneapolis, MN, USA)-based 'patient-specific' algorithm that included a restrictive red cell transfusion threshold (haematocrit 18%) or to a 'generic' non-NIRS-based algorithm (standard care). The NIRS algorithm aimed to maintain cerebral oxygenation at an absolute value of > 50% or at > 70% of baseline values. The primary outcome for the trial was cognitive function measured up to 3 months postsurgery., Results: The analysis population comprised eligible randomized patients who underwent valve or combined valve surgery and coronary artery bypass grafts using cardiopulmonary bypass between December 2009 and January 2014 ( n =98 patient-specific algorithm; n =106 generic algorithm). There was no difference between the groups for the three core cognitive domains (attention, verbal memory, and motor coordination) or for the non-core domains psychomotor speed and visuo-spatial skills. The NIRS group had higher scores for verbal fluency; mean difference 3.73 (95% confidence interval 1.50, 5.96). Red cell transfusions, biomarkers of brain, kidney, and myocardial injury, adverse events, and health-care costs were similar between the groups., Conclusions: These results do not support the use of NIRS-based algorithms for the personalized optimization of cerebral oxygenation in adult cardiac surgery., Clinical Trial Registration: http://www.controlled-trials.com , ISRCTN 23557269., (© The Author 2017. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com)

Health outcomes after out of hospital cardiac arrest (OHCA) are extremely poor, with only 7-9% of patients in the United Kingdom (UK) surviving to hospital discharge. Currently emergency medical services (EMS) use either tracheal intubation or newer supraglottic airway devices (SGAs) to provide advanced airway management during OHCA. Equipoise between the two techniques has led to calls for a well-designed randomised controlled trial. The primary objective of the AIRWAYS-2 trial is to assess whether the clinical effectiveness of the i-gel, a second-generation SGA, is superior to tracheal intubation in the initial airway management of OHCA patients in the UK. Paramedics recruited to the AIRWAYS-2 trial are randomised to use either tracheal intubation or i-gel as their first advanced airway intervention. Adults who have had a non-traumatic OHCA and are attended by an AIRWAYS-2 paramedic are retrospectively assessed against eligibility criteria for inclusion. The primary outcome is the modified Rankin Scale score at hospital discharge. Secondary objectives are to: (i) estimate differences between groups in outcome measures relating to airway management, hospital stay and recovery at 3 and 6 months; (ii) estimate the cost effectiveness of the i-gel compared to tracheal intubation. Because OHCA patient needs immediate treatment there are several unusual features and challenges to the design and implementation of this trial; these include level of randomisation, the automatic enrolment model, enrolment of patients that lack capacity and minimisation of bias. Patient enrolment began in June 2015. The trial will enrol 9070 patients over two years. The results are expected to influence future resuscitation guidelines. Trial Registration ISRCTN: 08256118., (Crown Copyright © 2016. Published by Elsevier Ireland Ltd. All rights reserved.)

Objective: To assess the incremental cost and cost-effectiveness of a restrictive versus a liberal red blood cell transfusion threshold after cardiac surgery., Design: A within-trial cost-effectiveness analysis with a 3-month time horizon, based on a multicentre superiority randomised controlled trial from the perspective of the National Health Service (NHS) and personal social services in the UK., Setting: 17 specialist cardiac surgery centres in UK NHS hospitals., Participants: 2003 patients aged >16 years undergoing non-emergency cardiac surgery with a postoperative haemoglobin of <9 g/dL., Interventions: Restrictive (transfuse if haemoglobin <7.5 g/dL) or liberal (transfuse if haemoglobin <9 g/dL) threshold during hospitalisation after surgery., Main Outcome Measures: Health-related quality of life measured using the EQ-5D-3L to calculate quality-adjusted life years (QALYs)., Results: The total costs from surgery up to 3 months were £17 945 and £18 127 in the restrictive and liberal groups (mean difference is -£182, 95% CI -£1108 to £744). The cost difference was largely attributable to the difference in the cost of red blood cells. Mean QALYs to 3 months were 0.18 in both groups (restrictive minus liberal difference is 0.0004, 95% CI -0.0037 to 0.0045). The point estimate for the base-case cost-effectiveness analysis suggested that the restrictive group was slightly more effective and slightly less costly than the liberal group and, therefore, cost-effective. However, there is great uncertainty around these results partly due to the negligible differences in QALYs gained., Conclusions: We conclude that there is no clear difference in the cost-effectiveness of restrictive and liberal thresholds for red blood cell transfusion after cardiac surgery., Trial Registration Number: ISRCTN70923932; Results., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Background: Uncertainty about optimal red blood cell transfusion thresholds in cardiac surgery is reflected in widely varying transfusion rates between surgeons and cardiac centres., Objective: To test the hypothesis that a restrictive compared with a liberal threshold for red blood cell transfusion after cardiac surgery reduces post-operative morbidity and health-care costs., Design: Multicentre, parallel randomised controlled trial and within-trial cost-utility analysis from a UK NHS and Personal Social Services perspective. We could not blind health-care staff but tried to blind participants. Random allocations were generated by computer and minimised by centre and operation., Setting: Seventeen specialist cardiac surgery centres in UK NHS hospitals., Participants: Patients aged > 16 years undergoing non-emergency cardiac surgery with post-operative haemoglobin < 9 g/dl. Exclusion criteria were: unwilling to have transfusion owing to beliefs; platelet, red blood cell or clotting disorder; ongoing or recurrent sepsis; and critical limb ischaemia., Interventions: Participants in the liberal group were eligible for transfusion immediately after randomisation (post-operative haemoglobin < 9 g/dl); participants in the restrictive group were eligible for transfusion if their post-operative haemoglobin fell to < 7.5 g/dl during the index hospital stay., Main Outcome Measures: The primary outcome was a composite outcome of any serious infectious (sepsis or wound infection) or ischaemic event (permanent stroke, myocardial infarction, gut infarction or acute kidney injury) during the 3 months after randomisation. Events were verified or adjudicated by blinded personnel. Secondary outcomes included blood products transfused; infectious events; ischaemic events; quality of life (European Quality of Life-5 Dimensions); duration of intensive care or high-dependency unit stay; duration of hospital stay; significant pulmonary morbidity; all-cause mortality; resource use, costs and cost-effectiveness., Results: We randomised 2007 participants between 15 July 2009 and 18 February 2013; four withdrew, leaving 1000 and 1003 in the restrictive and liberal groups, respectively. Transfusion rates after randomisation were 53.4% (534/1000) and 92.2% (925/1003). The primary outcome occurred in 35.1% (331/944) and 33.0% (317/962) of participants in the restrictive and liberal groups [odds ratio (OR) 1.11, 95% confidence interval (CI) 0.91 to 1.34; p = 0.30], respectively. There were no subgroup effects for the primary outcome, although some sensitivity analyses substantially altered the estimated OR. There were no differences for secondary clinical outcomes except for mortality, with more deaths in the restrictive group (4.2%, 42/1000 vs. 2.6%, 26/1003; hazard ratio 1.64, 95% CI 1.00 to 2.67; p = 0.045). Serious post-operative complications excluding primary outcome events occurred in 35.7% (354/991) and 34.2% (339/991) of participants in the restrictive and liberal groups, respectively. The total cost per participant from surgery to 3 months postoperatively differed little by group, just £182 less (standard error £488) in the restrictive group, largely owing to the difference in red blood cells cost. In the base-case cost-effectiveness results, the point estimate suggested that the restrictive threshold was cost-effective; however, this result was very uncertain partly owing to the negligible difference in quality-adjusted life-years gained., Conclusions: A restrictive transfusion threshold is not superior to a liberal threshold after cardiac surgery. This finding supports restrictive transfusion due to reduced consumption and costs of red blood cells. However, secondary findings create uncertainty about recommending restrictive transfusion and prompt a new hypothesis that liberal transfusion may be superior after cardiac surgery. Reanalyses of existing trial datasets, excluding all participants who did not breach the liberal threshold, followed by a meta-analysis of the reanalysed results are the most obvious research steps to address the new hypothesis about the possible harm of red blood cell transfusion., Trial Registration: Current Controlled Trials ISRCTN70923932., 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. 20, No. 60. See the NIHR Journals Library website for further project information.

Introduction: Severely bleeding trauma patients are a small proportion of the major trauma population but account for 40% of all trauma deaths. Healthcare resource use and costs are likely to be substantial but have not been fully quantified. Knowledge of costs is essential for developing targeted cost reduction strategies, informing health policy, and ensuring the cost-effectiveness of interventions., Methods: In collaboration with the Trauma Audit Research Network (TARN) detailed patient-level data on in-hospital resource use, extended care at hospital discharge, and readmissions up to 12 months post-injury were collected on 441 consecutive adult major trauma patients with severe bleeding presenting at 22 hospitals (21 in England and one in Wales). Resource use data were costed using national unit costs and mean costs estimated for the cohort and for clinically relevant subgroups. Using nationally available data on trauma presentations in England, patient-level cost estimates were up-scaled to a national level., Results: The mean (95% confidence interval) total cost of initial hospital inpatient care was £19,770 (£18,177 to £21,364) per patient, of which 62% was attributable to ventilation, intensive care, and ward stays, 16% to surgery, and 12% to blood component transfusion. Nursing home and rehabilitation unit care and re-admissions to hospital increased the cost to £20,591 (£18,924 to £22,257). Costs were significantly higher for more severely injured trauma patients (Injury Severity Score ≥15) and those with blunt injuries. Cost estimates for England were £148,300,000, with over a third of this cost attributable to patients aged 65 years and over., Conclusions: Severely bleeding major trauma patients are a high cost subgroup of all major trauma patients, and the cost burden is projected to rise further as a consequence of an aging population and as evidence continues to emerge on the benefits of early and simultaneous administration of blood products in pre-specified ratios. The findings from this study provide a previously unreported baseline from which the potential impact of changes to service provision and/or treatment practice can begin to be evaluated. Further studies are still required to determine the full costs of post-discharge care requirements, which are also likely to be substantial.

Objectives: Data on costs associated with acute upper gastrointestinal bleeding (AUGIB) are scarce. We provide estimates of UK healthcare costs, indirect costs and health-related quality of life (HRQoL) for patients presenting to hospital with AUGIB., Setting: Six UK university hospitals with >20 AUGIB admissions per month, >400 adult beds, 24 h endoscopy, and on-site access to intensive care and surgery., Participants: 936 patients aged ≥18 years, admitted with AUGIB, and enrolled between August 2012 and March 2013 in the TRIGGER trial of AUGIB comparing restrictive versus liberal red blood cell (RBC) transfusion thresholds., Primary and Secondary Outcome Measures: Healthcare resource use during hospitalisation and postdischarge up to 28  days, unpaid informal care, time away from paid employment and HRQoL using the EuroQol EQ-5D at 28  days were measured prospectively. National unit costs were used to value resource use. Initial in-hospital treatment costs were upscaled to a UK level., Results: Mean initial in-hospital costs were £2458 (SE=£216) per patient. Inpatient bed days, endoscopy and RBC transfusions were key cost drivers. Postdischarge healthcare costs were £391 (£44) per patient. One-third of patients received unpaid informal care and the quarter in paid employment required time away from work. Mean HRQoL for survivors was 0.74. Annual initial inhospital treatment cost for all AUGIB cases in the UK was estimated to be £155.5 million, with exploratory analyses of the incremental costs of treating hospitalised patients developing AUGIB generating figures of between £143 million and £168 million., Conclusions: AUGIB is a large burden for UK hospitals with inpatient stay, endoscopy and RBC transfusions as the main cost drivers. It is anticipated that this work will enable quantification of the impact of cost reduction strategies in AUGIB and will inform economic analyses of novel or existing interventions for AUGIB., Trial Registration Number: ISRCTN85757829 and NCT02105532., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: Whether a restrictive threshold for hemoglobin level in red-cell transfusions, as compared with a liberal threshold, reduces postoperative morbidity and health care costs after cardiac surgery is uncertain., Methods: We conducted a multicenter, parallel-group trial in which patients older than 16 years of age who were undergoing nonemergency cardiac surgery were recruited from 17 centers in the United Kingdom. Patients with a postoperative hemoglobin level of less than 9 g per deciliter were randomly assigned to a restrictive transfusion threshold (hemoglobin level <7.5 g per deciliter) or a liberal transfusion threshold (hemoglobin level <9 g per deciliter). The primary outcome was a serious infection (sepsis or wound infection) or an ischemic event (permanent stroke [confirmation on brain imaging and deficit in motor, sensory, or coordination functions], myocardial infarction, infarction of the gut, or acute kidney injury) within 3 months after randomization. Health care costs, excluding the index surgery, were estimated from the day of surgery to 3 months after surgery., Results: A total of 2007 patients underwent randomization; 4 participants withdrew, leaving 1000 in the restrictive-threshold group and 1003 in the liberal-threshold group. Transfusion rates after randomization were 53.4% and 92.2% in the two groups, respectively. The primary outcome occurred in 35.1% of the patients in the restrictive-threshold group and 33.0% of the patients in the liberal-threshold group (odds ratio, 1.11; 95% confidence interval [CI], 0.91 to 1.34; P=0.30); there was no indication of heterogeneity according to subgroup. There were more deaths in the restrictive-threshold group than in the liberal-threshold group (4.2% vs. 2.6%; hazard ratio, 1.64; 95% CI, 1.00 to 2.67; P=0.045). Serious postoperative complications, excluding primary-outcome events, occurred in 35.7% of participants in the restrictive-threshold group and 34.2% of participants in the liberal-threshold group. Total costs did not differ significantly between the groups., Conclusions: A restrictive transfusion threshold after cardiac surgery was not superior to a liberal threshold with respect to morbidity or health care costs. (Funded by the National Institute for Health Research Health Technology Assessment program; Current Controlled Trials number, ISRCTN70923932.).

Background: This cost analysis uses data from a randomized trial comparing a no prophylaxis versus prophylactic platelet (PLT) transfusion policy (counts <10 × 10(9) /L) in adult patients with hematologic malignancies. Results are presented for all patients and separately for autologous hematopoietic stem cell transplantation (HSCT) (autoHSCT) and chemotherapy/allogeneic HSCT (chemo/alloHSCT) patients., Study Design and Methods: Data were collected to 30 days on PLT and red blood cell (RBC) transfusions, major bleeds, serious adverse events, critical care, and hematology ward stay. Data were costed using 2011 to 2012 UK unit costs and converted into US$. Sensitivity analyses were performed on uncertain cost variables., Results: Across the whole trial no prophylaxis saved costs compared to prophylaxis: -$1760 per patient (95% confidence interval [CI], -$3250 to -$249; p < 0.05). For autoHSCT patients there was no cost difference between arms: -$110 per patient (95% CI, -$1648 to $1565; p = 0.89). For chemo/alloHSCT patients no prophylaxis cost significantly less than prophylaxis: -$5686 per patient (95% CI, -$8580 to -$2853; p < 0.01). The cost impact of no prophylaxis differed significantly between subgroups. Sensitivity analyses varying daily treatment costs and ward stay for chemo/alloHSCT patients reduced cost differences to -$941 per patient (p = 0.21) across the whole trial and -$2927 per patient (p < 0.05) in chemo/alloHSCT subgroup., Conclusions: It is unclear whether a no-prophylaxis policy saves costs overall. In chemo/alloHSCT patients cost savings are apparent but their magnitude is sensitive to a number of variables and must be considered alongside clinical data showing increased bleeding rates. In autoHSCT patients savings generated through lower PLT use in no-prophylaxis arm were offset by cost increases elsewhere, for example, additional RBC transfusions. Cost-effectiveness analyses of alternative PLT transfusion policies simultaneously considering costs and patient-reported outcomes are warranted., (© 2014 AABB.)

Thresholds for red blood cell transfusion following cardiac surgery vary by hospital and surgeon. The TITRe2 multi-centre randomised controlled trial aims to randomise 2000 patients from 17 United Kingdom centres, and tests the hypothesis that a restrictive transfusion threshold will reduce postoperative morbidity and health service costs compared to a liberal threshold. Patients consent to take part in the study pre-operatively but are only randomised if their haemoglobin falls below 9 g/dL during their post-operative hospital stay. The primary outcome is a binary composite outcome of any serious infectious or ischaemic event in the first three months after randomisation. Many challenges have been encountered in the set-up and running of the study., (Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Acute upper gastrointestinal bleeding (AUGIB) is the commonest reason for hospitalization with hemorrhage in the UK and the leading indication for transfusion of red blood cells (RBCs). Observational studies suggest an association between more liberal RBC transfusion and adverse patient outcomes, and a recent randomised trial reported increased further bleeding and mortality with a liberal transfusion policy. TRIGGER (Transfusion in Gastrointestinal Bleeding) is a pragmatic, cluster randomized trial which aims to evaluate the feasibility and safety of implementing a restrictive versus liberal RBC transfusion policy in adult patients admitted with AUGIB. The trial will take place in 6 UK hospitals, and each centre will be randomly allocated to a transfusion policy. Clinicians throughout each hospital will manage all eligible patients according to the transfusion policy for the 6-month trial recruitment period. In the restrictive centers, patients become eligible for RBC transfusion when their hemoglobin is <8 g/dL. In the liberal centers patients become eligible for transfusion once their hemoglobin is <10 g/dL. All clinicians will have the discretion to transfuse outside of the policy but will be asked to document the reasons for doing so. Feasibility outcome measures include protocol adherence, recruitment rate, and evidence of selection bias. Clinical outcome measures include further bleeding, mortality, thromboembolic events, and infections. Quality of life will be measured using the EuroQol EQ-5D at day 28, and the costs associated with hospitalization for AUGIB in the UK will be estimated. Consent will be sought from participants or their representatives according to patient capacity for use of routine hospital data and day 28 follow up. The study has ethical approval for conduct in England and Scotland. Results will be analysed according to a pre-defined statistical analysis plan and disseminated in peer reviewed publications to relevant stakeholders. The results of this study will inform the feasibility and design of a phase III randomized trial., (Copyright © 2013 Elsevier Inc. All rights reserved.)

In this study, factors that influence a person's likelihood of hiring a pediatric health care advocate (HCA) for support and/or advisory services were examined. Participants were asked to read vignettes in which a child's symptom severity, probability of mortality, and age were manipulated. A significantly higher likelihood of hiring an HCA for advisory services than for support services was found. A significant interaction between level of mortality and type of service indicated that when mortality was depicted as high, participants reported a greater likelihood of hiring an HCA for support services than for advisory services.

Introduction: In response to the increasing complexity of the health care system, the field of health care advocacy has emerged. However, little is known about variables that may influence a person's likelihood of hiring a health care advocate (HCA) for their chronically ill child., Methods: Severity (high or low) and probability of mortality (high or low) of a child's chronic illness and the child's age (1, 7, or 13 years) were manipulated using vignettes. The dependent variable was a composite score of the eight items used to measure the participants' likelihood of hiring an HCA., Results: Participants (N = 1052) were more likely to hire an HCA for a child who was 1 year old than for a child who was 13 years old. Participants were more likely to hire an HCA for a child whose chronic illness was low rather than high in severity and whose chronic illness was high rather than low in probability of mortality., Discussion: Use of an HCA may increase patient satisfaction, decrease medical errors, and enhance pediatric health outcomes., (Copyright © 2012 National Association of Pediatric Nurse Practitioners. Published by Mosby, Inc. All rights reserved.)

We review the literature on the prevalence and conditions resulting in overweight and obesity in people with intellectual disability (ID), followed by obesity treatment research with typically developing children and adaptations for children with ID. In addition to proposing directions for future research and practice, we report a comprehensive randomized control trial (RCT) of family-based behavioral intervention targeting weight loss among adolescents with Down syndrome.

Objective: Local steroid injections and community-based physiotherapy have been shown to be of similar benefit for treating shoulder pain presenting to primary care. This paper presents a cost consequences analysis of a prospective economic evaluation, conducted alongside a randomized clinical trial (RCT) of corticosteroid injections versus physiotherapy for new episodes of unilateral shoulder pain, to determine the economic implications of injection versus physiotherapy., Methods: A pragmatic RCT with 207 patients randomized to either physiotherapy (n = 103) or local steroid injection (n = 104) was conducted. The resource inputs required were identified for each treatment arm in terms of capital, staff and consumables. These were measured for the period up to 6 months post-randomization. Outcome measures included shoulder disability, shoulder pain, global assessment of health change and the EQ5D, all at 6 months. A sensitivity analysis was performed around the general practitioner minor surgical fee., Results: Analysis is presented on the 199 patients for which the general practice record review (101 physiotherapy, 98 injection) was available. The total mean costs, per patient, were 71.28 pound sterling for the injection group and 114.60 pound sterling for the physiotherapy group. The difference in average total cost per patient was 43.32 pound sterling (95% bootstrap confidence interval: 16.21 pound sterling, 68.03 pound sterling ). This is a statistically significant difference in cost. Outcome was similar in both groups across all measures following intervention. Smaller mean differences in cost were observed between the treatment groups in the sensitivity analysis, but the difference remained in favour of injection over physiotherapy., Conclusions: This study has shown, given similar clinical outcomes across the treatment groups, that corticosteroid injections were the cost-effective option for patients presenting with new episodes of unilateral shoulder pain in primary care.

Objectives: Chondral defects of the knee cartilage are prevalent. Autologous chondrocyte implantation (ACI) and mosaicplasty are increasingly used to treat symptomatic knee defects. This study assessed the costs and health status outcomes after ACI and mosaicplasty., Methods: Patients were eligible to participate in this cross-sectional study if they received ACI or mosaicplasty at the Royal National Orthopaedic Hospital between 1997 and 2001 or were on a waiting list for ACI. Secondary-care resource use was collected to 2 years postoperatively using a resource collection proforma. Participants responded to postal questions about sociodemographic characteristics and knee-related (Modified Cincinnati Knee Rating System) and general health status (EQ-5D)., Results: Fifty-three ACI, twenty mosaicplasty, and twenty-two patients waiting for ACI participated. The average cost per patient was higher for ACI (10,600 pounds sterling: 95 percent confidence interval [CI], 10,036 pounds sterling-11,214 pounds sterling) than mosaicplasty (7,948 pounds sterling: 95 percent CI, 6,957 pounds sterling-9,243 pounds sterling). Postoperatively, ACI and mosaicplasty patients (combined) experienced better health status than those waiting for ACI. ACI patients tended to have better health status outcomes than mosaicplasty patients (not statistically significant). Estimated average EQ-5D social tariff improvements for quality-adjusted life year (QALY) calculations were 0.23 (ACI) and 0.06 (mosaicplasty). Average costs per QALY were 23,043 pounds sterling (ACI) and 66,233 pounds sterling (mosaicplasty). The incremental cost effectiveness ratio (ICER) for providing ACI over mosaicplasty was 16,349 pounds sterling., Conclusions: Average costs were higher for ACI than mosaicplasty. However, both the estimated cost per QALY and ICER for providing ACI over mosaicplasty fell beneath an implicit English funding threshold of 30,000 pounds sterling per QALY. Prospective studies should include measures of utility to confirm the estimated cost utility ratios of ACI and mosaicplasty.

Endocrine disrupting compounds (EDCs), especially those that are estrogenic, are an issue of growing concern because they may ultimately adversely affect wildlife survival. 17-beta-Estradiol and its synthetic counterpart, 17-alpha-ethinylestradiol, two common EDCs, are associated with intersex conditions and impaired male reproductive behavior in fish. Male and female Japanese medaka (Oryzias latipes) were exposed to 10 ng/l ethinylestradiol for 6 months. Using terminal dideoxynucleotidyl-mediated dUTP nick end-labeling (TUNEL) to quantitate cell death, we found that ethinylestradiol-exposed males had significantly fewer apoptotic cells in the forebrain compared to untreated males and exposed females. Our results show that the effects of ethinylestradiol exposure are highly variable among individuals of the same species and even within tissues of the same individual. Thus, when examining the effects of EDCs on natural populations, data from a variety of tissues should be examined and the interpretation of any effects should include consideration of tissue-specific processes.