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IntroductionMesothelioma 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 analysisThe 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 disseminationResearch 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 numbersISRCTN—ISRCTN44351742 and ClinicalTrials.gov—NCT02040272.

BackgroundTotal hip arthroplasty (THA) is a highly effective procedure for improving pain and function in patients with advanced joint degeneration; however, revision surgery may be required because of complications or implant wear. Revision THA (rTHA) has a higher in-hospital mortality rate, longer hospital length of stay, are at higher risk of re-revision surgery and have worse physical and mental health outcome measures compared with primary THAs. The introduction of specialist revision hubs also means that patients frequently travel further for surgery. No specific guidelines have been established for rehabilitation after rTHA, leading to large variations in practice and potentially inadequate provision. We hypothesise that delivering a tailored physiotherapy intervention will improve and sustain greater functional outcomes and health-related quality of life compared with standard protocols currently in place. The aim of this study is to determine the feasibility and explore the acceptability of a trial investigating the effectiveness of a tailored physiotherapy intervention after rTHA.Methods and analysisMulticentre, parallel two-arm feasibility randomised controlled trial with an embedded qualitative study. A total of 60 participants will be recruited from at least four UK NHS secondary care hospitals and randomly allocated (1:1 ratio) to either the tailored physiotherapy rehabilitation (THRIVE) programme or a standardised usual care arm. Eligible adults will be undergoing a single or final stage rTHA and participating in outpatient physiotherapy. Feasibility outcomes include recruitment rate, retention rate, adherence rate, intervention fidelity, outcome measure completion and acceptability of the intervention. Research assessments consisting of patient-reported and performance-based measures will occur preoperatively (baseline), with follow-ups at 4 and 8 months postoperatively. Feasibility data will be analysed using descriptive statistics. The embedded qualitative study will include trial participants and physiotherapists from the THRIVE arm to explore their experience of the trial and understand measures to improve the delivery of a future trial.Ethics and disseminationThe study has received ethical approval (West of Scotland REC 25/WS/0080), and all participants will provide informed consent. It will assess trial feasibility while exploring operational and safety challenges, including recruitment barriers and the potential value of a hub-and-spoke model for delivering physiotherapy. Findings will be disseminated through trial registry reporting, peer-reviewed open-access publication, conference presentations and participant summaries, with reporting aligned to CONSORT guidelines for pilot and feasibility trials.Trial registration number ISRCTN10649335.

IntroductionLung 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 analysisThe 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 disseminationThis 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

IntroductionLung 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 analysisRAMON 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 disseminationThe 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 numberISRCTN11613852.

In this study, patients were randomly assigned to a transfusion threshold of 9 or 7.5 g per deciliter after cardiac surgery. There was no significant between-group difference in infectious or ischemic events, but more deaths were associated with the lower threshold. Perioperative anemia is common after cardiac surgery and is associated with significant increases in morbidity and mortality. 1 – 3 The transfusion of allogeneic red cells is the preferred treatment for acute anemia and is also used in patients undergoing cardiac surgery; typically, more than 50% of patients receive a perioperative transfusion, 4 , 5 which uses a substantial proportion of blood supplies. 6 Observational studies suggest that transfusion is harmful after cardiac surgery; associations have been reported between transfusion and infection, low cardiac output, acute kidney injury, and death. 2 , 7 , 8 In contrast, randomized, controlled trials of red-cell transfusion with restrictive thresholds (i.e., transfusions . . .

IntroductionGabapentin 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 analysisThe 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 disseminationThis 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 numberISRCTN63614165.

ObjectiveTo identify the key drivers of cost-effectiveness for cardiovascular magnetic resonance (CMR) when patients activate the primary percutaneous coronary intervention (PPCI) pathway.DesignEconomic 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.SettingUsual care (with or without CMR) in the NHS.ParticipantsPatients 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.InterventionsModel 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 measuresKey drivers of cost-effectiveness for CMR, incremental costs and quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios.ResultsIn 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.ConclusionsIf 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.

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: 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: 95 percent confidence interval [CI], £10,036–£11,214) than mosaicplasty (£7,948: 95 percent CI, £6,957–£9,243). 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 (ACI) and £66,233 (mosaicplasty). The incremental cost effectiveness ratio (ICER) for providing ACI over mosaicplasty was £16,349. 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 per QALY. Prospective studies should include measures of utility to confirm the estimated cost utility ratios of ACI and mosaicplasty.

Provision of safe drinking water in the United States is a great public health achievement. However, new waterborne disease challenges have emerged (e.g., aging infrastructure, chlorine-tolerant and biofilm-related pathogens, increased recreational water use). Comprehensive estimates of the health burden for all water exposure routes (ingestion, contact, inhalation) and sources (drinking, recreational, environmental) are needed. We estimated total illnesses, emergency department (ED) visits, hospitalizations, deaths, and direct healthcare costs for 17 waterborne infectious diseases. About 7.15 million waterborne illnesses occur annually (95% credible interval [CrI] 3.88 million-12.0 million), results in 601,000 ED visits (95% CrI 364,000-866,000), 118,000 hospitalizations (95% CrI 86,800-150,000), and 6,630 deaths (95% CrI 4,520-8,870) and incurring US $3.33 billion (95% CrI 1.37 billion-8.77 billion) in direct healthcare costs. Otitis externa and norovirus infection were the most common illnesses. Most hospitalizations and deaths were caused by biofilm-associated pathogens (nontuberculous mycobacteria, Pseudomonas, Legionella), costing US $2.39 billion annually.