Improving risk models for patients having emergency bowel cancer surgery using linked electronic health records: a national cohort study.

BACKGROUND: Life-saving emergency major resection of colorectal cancer (CRC) is a high-risk procedure. Accurate prediction of postoperative mortality for patients undergoing this procedure is essential for both healthcare performance monitoring and preoperative risk assessment. Risk-adjustment models for CRC patients often include patient and tumour characteristics, widely available in cancer registries and audits. The authors investigated to what extent inclusion of additional physiological and surgical measures, available through linkage or additional data collection, improves accuracy of risk models. METHODS: Linked, routinely-collected data on patients undergoing emergency CRC surgery in England between December 2016 and November 2019 were used to develop a risk model for 90-day mortality. Backwards selection identified a 'selected model' of physiological and surgical measures in addition to patient and tumour characteristics. Model performance was assessed compared to a 'basic model' including only patient and tumour characteristics. Missing data was multiply imputed. RESULTS: Eight hundred forty-six of 10 578 (8.0%) patients died within 90 days of surgery. The selected model included seven preoperative physiological and surgical measures (pulse rate, systolic blood pressure, breathlessness, sodium, urea, albumin, and predicted peritoneal soiling), in addition to the 10 patient and tumour characteristics in the basic model (calendar year of surgery, age, sex, ASA grade, TNM T stage, TNM N stage, TNM M stage, cancer site, number of comorbidities, and emergency admission). The selected model had considerably better discrimination compared to the basic model (C-statistic: 0.824 versus 0.783, respectively). CONCLUSION: Linkage of disease-specific and treatment-specific datasets allowed the inclusion of physiological and surgical measures in a risk model alongside patient and tumour characteristics, which improves the accuracy of the prediction of the mortality risk for CRC patients having emergency surgery. This improvement will allow more accurate performance monitoring of healthcare providers and enhance clinical care planning.

Effectiveness of GRACE risk score in patients admitted to hospital with non-ST elevation acute coronary syndrome (UKGRIS): parallel group cluster randomised controlled trial.

OBJECTIVE: To determine the effectiveness of risk stratification using the Global Registry of Acute Coronary Events (GRACE) risk score (GRS) for patients presenting to hospital with suspected non-ST elevation acute coronary syndrome. DESIGN: Parallel group cluster randomised controlled trial. SETTING: Patients presenting with suspected non-ST elevation acute coronary syndrome to 42 hospitals in England between 9 March 2017 and 30 December 2019. PARTICIPANTS: Patients aged ≥18 years with a minimum follow-up of 12 months. INTERVENTION: Hospitals were randomised (1:1) to patient management by standard care or according to the GRS and associated guidelines. MAIN OUTCOME MEASURES: Primary outcome measures were use of guideline recommended management and time to the composite of cardiovascular death, non-fatal myocardial infarction, new onset heart failure hospital admission, and readmission for cardiovascular event. Secondary measures included the duration of hospital stay, EQ-5D-5L (five domain, five level version of the EuroQoL index), and the composite endpoint components. RESULTS: 3050 participants (1440 GRS, 1610 standard care) were recruited in 38 UK clusters (20 GRS, 18 standard care). The mean age was 65.7 years (standard deviation 12), 69% were male, and the mean baseline GRACE scores were 119.5 (standard deviation 31.4) and 125.7 (34.4) for GRS and standard care, respectively. The uptake of guideline recommended processes was 77.3% for GRS and 75.3% for standard care (odds ratio 1.16, 95% confidence interval 0.70 to 1.92, P=0.56). The time to the first composite cardiac event was not significantly improved by the GRS (hazard ratio 0.89, 95% confidence interval 0.68 to 1.16, P=0.37). Baseline adjusted EQ-5D-5L utility at 12 months (difference -0.01, 95% confidence interval -0.06 to 0.04) and the duration of hospital admission within 12 months (mean 11.2 days, standard deviation 18 days v 11.8 days, 19 days) were similar for GRS and standard care. CONCLUSIONS: In adults presenting to hospital with suspected non-ST elevation acute coronary syndrome, the GRS did not improve adherence to guideline recommended management or reduce cardiovascular events at 12 months. TRIAL REGISTRATION: ISRCTN 29731761.

Contrasting principal stratum and hypothetical strategy estimands in multi-period crossover trials with incomplete data.

Complete case analyses of complete crossover designs provide an opportunity to make comparisons based on patients who can tolerate all treatments. It is argued that this provides a means of estimating a principal stratum strategy estimand, something which is difficult to do in parallel group trials. While some trial users will consider this a relevant aim, others may be interested in hypothetical strategy estimands, that is, the effect that would be found if all patients completed the trial. Whether these estimands differ importantly is a question of interest to the different users of the trial results. This paper derives the difference between principal stratum strategy and hypothetical strategy estimands, where the former is estimated by a complete-case analysis of the crossover design, and a model for the dropout process is assumed. Complete crossover designs, that is, those where all treatments appear in all sequences, and which compare t treatments over p periods with respect to a continuous outcome are considered. Numerical results are presented for Williams designs with four and six periods. Results from a trial of obstructive sleep apnoea-hypopnoea (TOMADO) are also used for illustration. The results demonstrate that the percentage difference between the estimands is modest, exceeding 5% only when the trial has been severely affected by dropouts or if the within-subject correlation is low.

Linkage of multiple electronic health record datasets using a 'spine linkage' approach compared with all 'pairwise linkages'.

BACKGROUND: Methods for linking records between two datasets are well established. However, guidance is needed for linking more than two datasets. Using all 'pairwise linkages'-linking each dataset to every other dataset-is the most inclusive, but resource-intensive, approach. The 'spine' approach links each dataset to a designated 'spine dataset', reducing the number of linkages, but potentially reducing linkage quality. METHODS: We compared the pairwise and spine linkage approaches using real-world data on patients undergoing emergency bowel cancer surgery between 31 October 2013 and 30 April 2018. We linked an administrative hospital dataset (Hospital Episode Statistics; HES) capturing patients admitted to hospitals in England, and two clinical datasets comprising patients diagnosed with bowel cancer and patients undergoing emergency bowel surgery. RESULTS: The spine linkage approach, with HES as the spine dataset, created an analysis cohort of 15 826 patients, equating to 98.3% of the 16 100 patients identified using the pairwise linkage approach. There were no systematic differences in patient characteristics between these analysis cohorts. Associations of patient and tumour characteristics with mortality, complications and length of stay were not sensitive to the linkage approach. When eligibility criteria were applied before linkage, spine linkage included 14 509 patients (90.0% compared with pairwise linkage). CONCLUSION: Spine linkage can be used as an efficient alternative to pairwise linkage if case ascertainment in the spine dataset and data quality of linkage variables are high. These aspects should be systematically evaluated in the nominated spine dataset before spine linkage is used to create the analysis cohort.

Mediation of the total effect of cystic fibrosis-related diabetes on mortality: A UK Cystic Fibrosis Registry cohort study.

AIM: To investigate whether the effect of cystic fibrosis-related diabetes (CFRD) on the composite outcome of mortality or transplant could act through lung function, pulmonary exacerbations and/or nutritional status. METHODS: A retrospective cohort of adult cystic fibrosis (CF) patients who had not been diagnosed with CFRD were identified from the UK Cystic Fibrosis Registry (n = 2750). Rate of death or transplant was compared between patients who did and did not develop CFRD (with insulin use) during follow-up using Poisson regression, separately by sex. Causal mediation methods were used to investigate whether lung function, pulmonary exacerbations and nutritional status lie on the causal pathway between insulin-treated CFRD and mortality/transplant. RESULTS: At all ages, the mortality/transplant rate was higher in both men and women diagnosed with CFRD. Pulmonary exacerbations were the strongest mediator of the effect of CFRD on mortality/transplant, with an estimated 15% [95% CI: 7%, 28%] of the effect at 2 years post-CFRD diagnosis attributed to exacerbations, growing to 24% [95% CI: 9%, 46%] at 4 years post-diagnosis. Neither lung function nor nutritional status were found to be significant mediators of this effect. Estimates were similar but with wider confidence intervals in a cohort that additionally included people with CFRD but not using insulin. CONCLUSION: There is evidence that pulmonary exacerbations mediate the effect of CFRD on mortality but, as they are estimated to mediate less than one-quarter of the total effect, the mechanism through which CFRD influences survival may involve other factors.

Impact of changes to the interscreening interval and faecal immunochemical test threshold in the national bowel cancer screening programme in England: results from the FIT pilot study.

INTRODUCTION: The NHS Bowel Cancer Screening Programme (BCSP) faces endoscopy capacity challenges from the COVID-19 pandemic and plans to lower the screening starting age. This may necessitate modifying the interscreening interval or threshold. METHODS: We analysed data from the English Faecal Immunochemical Testing (FIT) pilot, comprising 27,238 individuals aged 59-75, screened for colorectal cancer (CRC) using FIT. We estimated screening sensitivity to CRC, adenomas, advanced adenomas (AA) and mean sojourn time of each pathology by faecal haemoglobin (f-Hb) thresholds, then predicted the detection of these abnormalities by interscreening interval and f-Hb threshold. RESULTS: Current 2-yearly screening with a f-Hb threshold of 120 µg/g was estimated to generate 16,092 colonoscopies, prevent 186 CRCs, detect 1142 CRCs, 7086 adenomas and 4259 AAs per 100,000 screened over 15 years. A higher threshold at 180 µg/g would reduce required colonoscopies to 11,500, prevent 131 CRCs, detect 1077 CRCs, 4961 adenomas and 3184 AAs. A longer interscreening interval of 3 years would reduce required colonoscopies to 10,283, prevent 126 and detect 909 CRCs, 4796 adenomas and 2986 AAs. CONCLUSION: Increasing the f-Hb threshold was estimated to be more efficient than increasing the interscreening interval regarding overall colonoscopies per screen-benefited cancer. Increasing the interval was more efficient regarding colonoscopies per cancer prevented.

Time-varying Comparison of All-cause Mortality After Liver Transplantation Between Recipients With and Without Hepatocellular Carcinoma: A Population-based Cohort Study Using the United Kingdom Liver Transplant Registry.

BACKGROUND: Accurately identifying time-varying differences in the hazard of all-cause mortality after liver transplantation (LT) between recipients with and without hepatocellular carcinoma (HCC) may inform patient selection and organ allocation policies as well as post-LT surveillance protocols. METHODS: A UK population-based study was carried out using 9586 LT recipients. The time-varying association between HCC and post-LT all-cause mortality was estimated using an adjusted flexible parametric model (FPM) and expressed as hazard ratios (HRs). Differences in this association by transplant year were then investigated. Non-cancer-specific mortality was compared between HCC and non-HCC recipients using an adjusted subdistribution hazard model. RESULTS: The HR comparing HCC recipients with non-HCC recipients was below one immediately after LT (1-mo HR = 0.76; 95% confidence interval [CI], 0.59-0.99; P = 0.044). The HR then increased sharply to a maximum at 1.3 y (HR = 2.07; 95% CI, 1.70-2.52; P < 0.001) before decreasing. The hazard of death was significantly higher in HCC recipients than in non-HCC recipients between 4 mo and 7.4 y post-LT. There were no notable differences in the association between HCC and the post-LT hazard of death by transplant year. The estimated non-cancer-specific subdistribution HR for HCC was 0.93 (95% CI, 0.80-1.09; P = 0.390) and not found to vary over time. CONCLUSIONS: FPMs can provide a more precise comparison of post-LT hazards of mortality between HCC and non-HCC patients. The results provide further evidence that some HCC patients have extra-hepatic spread at the time of LT, which has implications for optimal post-LT surveillance protocols.

Methods of analysis for survival outcomes with time-updated mediators, with application to longitudinal disease registry data.

Mediation analysis is a useful tool to illuminate the mechanisms through which an exposure affects an outcome but statistical challenges exist with time-to-event outcomes and longitudinal observational data. Natural direct and indirect effects cannot be identified when there are exposure-induced confounders of the mediator-outcome relationship. Previous measurements of a repeatedly-measured mediator may themselves confound the relationship between the mediator and the outcome. To overcome these obstacles, two recent methods have been proposed, one based on path-specific effects and one based on an additive hazards model and the concept of exposure splitting. We investigate these techniques, focusing on their application to observational datasets. We apply both methods to an analysis of the UK Cystic Fibrosis Registry dataset to identify how much of the relationship between onset of cystic fibrosis-related diabetes and subsequent survival acts through pulmonary function. Statistical properties of the methods are investigated using simulation. Both methods produce unbiased estimates of indirect and direct effects in scenarios consistent with their stated assumptions but, if the data are measured infrequently, estimates may be biased. Findings are used to highlight considerations in the interpretation of the observational data analysis.

Five-year results of Amaze: a randomized controlled trial of adjunct surgery for atrial fibrillation.

OBJECTIVES: The Amaze trial showed that adding atrial fibrillation (AF) surgery to cardiac operations increased return to sinus rhythm (SR) without impact on quality of life or survival at 2 years. We report outcomes to 5 years. METHODS: In a multicentre, phase III, pragmatic, double-blind, randomized controlled superiority trial, cardiac surgery patients with >3 months of AF were randomized 1:1 to adjunct AF surgery or control. Primary outcomes of 1-year SR restoration and 2-year quality-adjusted survival were already reported. This study reports on rhythm, survival, quality-adjusted survival, stroke, medication and safety to 5 years. RESULTS: Between 2009 and 2014, 352 patients were randomized. By 5 years 79 died, 58 withdrew, 34 were lost to follow-up and the remaining 182 provided data. AF surgery significantly increased the odds of remaining in SR at 5 years {odds ratio = 2.98 [95% confidence interval (CI) 1.23, 7.17], P = 0.015}. There was a non-significant decrease in stroke incidence [odds ratio = 0.605 (95% CI 0.284, 1.287), P = 0.19], but no improved survival [5-year survival: AF surgery 77.3% (95% CI 71.1%, 83.5%), controls 77.8% (95% CI 71.7%, 84.0%), P = 0.85]. Quality-adjusted survival difference was negligible (-0.03; 95% CI -0.33, 0.27, P = 0.85). The composite of survival free of stroke and AF was better in the AF surgery group [odds ratio = 2.34 (95% CI 1.03, 5.31)]. There were no other differences. CONCLUSIONS: Adjunct AF surgery confers a higher rate of SR to 5 years and a better composite outcome of survival free of stroke and AF but has no impact on overall or quality-adjusted survival or other clinical outcomes. CLINICAL TRIAL REGISTRATION NUMBER: ISRCTN82731440.

Reference Case Methods for Expert Elicitation in Health Care Decision Making.

BACKGROUND: The evidence used to inform health care decision making (HCDM) is typically uncertain. In these situations, the experience of experts is essential to help decision makers reach a decision. Structured expert elicitation (referred to as elicitation) is a quantitative process to capture experts' beliefs. There is heterogeneity in the existing elicitation methodology used in HCDM, and it is not clear if existing guidelines are appropriate for use in this context. In this article, we seek to establish reference case methods for elicitation to inform HCDM. METHODS: We collated the methods available for elicitation using reviews and critique. In addition, we conducted controlled experiments to test the accuracy of alternative methods. We determined the suitability of the methods choices for use in HCDM according to a predefined set of principles for elicitation in HCDM, which we have also generated. We determined reference case methods for elicitation in HCDM for health technology assessment (HTA). RESULTS: In almost all methods choices available for elicitation, we found a lack of empirical evidence supporting recommendations. Despite this, it is possible to define reference case methods for HTA. The reference methods include a focus on gathering experts with substantive knowledge of the quantities being elicited as opposed to those trained in probability and statistics, eliciting quantities that the expert might observe directly, and individual elicitation of beliefs, rather than solely consensus methods. It is likely that there are additional considerations for decision makers in health care outside of HTA. CONCLUSIONS: The reference case developed here allows the use of different methods, depending on the decision-making setting. Further applied examples of elicitation methods would be useful. Experimental evidence comparing methods should be generated.

Probabilistic linkage without personal information successfully linked national clinical datasets.

BACKGROUND: Probabilistic linkage can link patients from different clinical databases without the need for personal information. If accurate linkage can be achieved, it would accelerate the use of linked datasets to address important clinical and public health questions. OBJECTIVE: We developed a step-by-step process for probabilistic linkage of national clinical and administrative datasets without personal information, and validated it against deterministic linkage using patient identifiers. STUDY DESIGN AND SETTING: We used electronic health records from the National Bowel Cancer Audit and Hospital Episode Statistics databases for 10,566 bowel cancer patients undergoing emergency surgery in the English National Health Service. RESULTS: Probabilistic linkage linked 81.4% of National Bowel Cancer Audit records to Hospital Episode Statistics, vs. 82.8% using deterministic linkage. No systematic differences were seen between patients that were and were not linked, and regression models for mortality and length of hospital stay according to patient and tumour characteristics were not sensitive to the linkage approach. CONCLUSION: Probabilistic linkage was successful in linking national clinical and administrative datasets for patients undergoing a major surgical procedure. It allows analysts outside highly secure data environments to undertake linkage while minimizing costs and delays, protecting data security, and maintaining linkage quality.

Faecal immunochemical testing in bowel cancer screening: Estimating outcomes for different diagnostic policies.

OBJECTIVES: The National Health Service Bowel Cancer Screening Programme (NHS BCSP) in England has replaced guaiac faecal occult blood testing by faecal immunochemical testing (FIT). There is interest in fully exploiting FIT measures to improve bowel cancer (CRC) screening strategies. In this paper, we estimate the relationship of the quantitative haemoglobin concentration provided by FIT in faecal samples with underlying pathology. From this we estimate thresholds required for given levels of sensitivity to CRC and high-risk adenomas (HRA). METHODS: Data were collected from a pilot study of FIT in England in 2014, in which 27,238 participants completed a FIT. Those with a faecal haemoglobin concentration (f-Hb) of at least 20 µg/g were referred for further investigation, usually colonoscopy. Truncated regression models were used to explore the relationship between bowel pathology and FIT results. Regression results were applied to estimate sensitivity to different abnormalities for a number of thresholds. RESULTS: Participants with CRC and HRA had significantly higher f-Hb, and this remained unchanged after adjusting for age and sex. While a threshold of 20 µg/g was estimated to capture 82.2% of CRC and 64.0% of HRA, this would refer 7.8% of participants for colonoscopy. The current programme threshold used in England of 120 µg/g was estimated to identify 47.8% of CRC and 25.0% of HRA. CONCLUSIONS: Under the current diagnostic policy of dichotomising FIT results, a very low threshold would be required to achieve high sensitivity to CRC and HRA, which would place further strain on colonoscopy resources. The NHS BCSP in England might benefit from a diagnostic policy that makes greater use of the quantitative nature of FIT.

Logistic regression and machine learning predicted patient mortality from large sets of diagnosis codes comparably.

OBJECTIVE: The objective of the study was to compare the performance of logistic regression and boosted trees for predicting patient mortality from large sets of diagnosis codes in electronic healthcare records. STUDY DESIGN AND SETTING: We analyzed national hospital records and official death records for patients with myocardial infarction (n = 200,119), hip fracture (n = 169,646), or colorectal cancer surgery (n = 56,515) in England in 2015-2017. One-year mortality was predicted from patient age, sex, and socioeconomic status, and 202 to 257 International Classification of Diseases 10th Revision codes recorded in the preceding year or not (binary predictors). Performance measures included the c-statistic, scaled Brier score, and several measures of calibration. RESULTS: One-year mortality was 17.2% (34,520) after myocardial infarction, 27.2% (46,115) after hip fracture, and 9.3% (5,273) after colorectal surgery. Optimism-adjusted c-statistics for the logistic regression models were 0.884 (95% confidence interval [CI]: 0.882, 0.886), 0.798 (0.796, 0.800), and 0.811 (0.805, 0.817). The equivalent c-statistics for the boosted tree models were 0.891 (95% CI: 0.889, 0.892), 0.804 (0.802, 0.806), and 0.803 (0.797, 0.809). Model performance was also similar when measured using scaled Brier scores. All models were well calibrated overall. CONCLUSION: In large datasets of electronic healthcare records, logistic regression and boosted tree models of numerous diagnosis codes predicted patient mortality comparably.

Rationale and design of the LIBERATES trial: Protocol for a randomised controlled trial of flash glucose monitoring for optimisation of glycaemia in individuals with type 2 diabetes and recent myocardial infarction.

Hyperglycaemia in individuals with type 2 diabetes (T2D) and myocardial infarction (MI) is associated with guarded clinical prognosis. Studies improving glucose levels in T2D following MI relied on HbA1c as the main glycaemic marker, failing to address potential adverse effects of hypoglycaemia and glucose variability. We describe the design of the LIBERATES trial that investigates the role of flash glucose monitoring in optimising glycaemic markers in high vascular risk individuals with T2D. This multicentre trial is designed to recruit up to 150 insulin and/or sulphonylurea-treated T2D patients, within 5 days of a proven MI. Individuals will be randomised 1:1 into intervention and control groups using flash glucose monitoring sensors and traditional self-monitoring of blood glucose, respectively. The control group will also wear a blinded continuous glucose monitoring sensor. The primary outcome is the difference in time spent in euglycaemia (defined as glucose levels between 3.9-10.0 mmol/l), comparing study groups 3 months following recruitment, assessed daily for 14 days and as an average. Secondary and exploratory end points include time spent in hypoglycaemia and hyperglycaemia, HbA1c, quality of life measures, major adverse cardiac events and cost-effectiveness of the intervention. This study will establish the role of flash glucose monitoring in glycaemic management of individuals with T2D sustaining a cardiac event.(Trial Registration: ISRCTN14974233, registered 12th June 2017).

A novel approach selected small sets of diagnosis codes with high prediction performance in large healthcare datasets.

OBJECTIVES: The objective of the study was to examine an approach for selecting small sets of diagnosis codes with high prediction performance in large datasets of electronic medical records. STUDY DESIGN AND SETTING: This was a modeling study using national hospital and mortality records for patients with myocardial infarction (n = 200,119), hip fracture (n = 169,646), or colorectal cancer surgery (n = 56,515) in England in 2015-2017. One-year mortality was predicted from ICD-10 codes recorded for at least 0.5% of patients using logistic regression ('full' models). An approximation method was used to select fewer codes that explained at least 95% of variation in full model predictions ('reduced' models). RESULTS: One-year mortality was 17.2% (34,520) after myocardial infarction, 27.2% (46,115) after hip fracture, and 9.3% (5,273) after colorectal surgery. Full models included 202, 257, and 209 ICD-10 codes in these populations. C-statistics for these models were 0.884 (95% confidence interval (CI) 0.882, 0.886), 0.798 (0.795, 0.800), and 0.810 (0.804, 0.817). Reduced models included 18, 33, and 41 codes and had c-statistics of 0.874 (95% CI 0.872, 0.876), 0.791 (0.788, 0.793), and 0.807 (0.801, 0.813). Performance was also similar when measured using Brier scores. All models were well calibrated. CONCLUSION: Our approach selected small sets of diagnosis codes that predicted patient outcomes comparably to large, comprehensive sets of codes.

One-year mortality of colorectal cancer patients: development and validation of a prediction model using linked national electronic data.

BACKGROUND: The existing literature does not provide a prediction model for mortality of all colorectal cancer patients using contemporary national hospital data. We developed and validated such a model to predict colorectal cancer death within 90, 180 and 365 days after diagnosis. METHODS: Cohort study using linked national cancer and death records. The development population included 27,480 patients diagnosed in England in 2015. The test populations were diagnosed in England in 2016 (n = 26,411) and Wales in 2015-2016 (n = 3814). Predictors were age, gender, socioeconomic status, referral source, performance status, tumour site, TNM stage and treatment intent. Cox regression models were assessed using Brier scores, c-indices and calibration plots. RESULTS: In the development population, 7.4, 11.7 and 17.9% of patients died from colorectal cancer within 90, 180 and 365 days after diagnosis. T4 versus T1 tumour stage had the largest adjusted association with the outcome (HR 4.67; 95% CI: 3.59-6.09). C-indices were 0.873-0.890 (England) and 0.856-0.873 (Wales) in the test populations, indicating excellent separation of predicted risks by outcome status. Models were generally well calibrated. CONCLUSIONS: The model was valid for predicting short-term colorectal cancer mortality. It can provide personalised information to support clinical practice and research.

MesoTRAP: a feasibility study that includes a pilot clinical trial comparing video-assisted thoracoscopic partial pleurectomy decortication with indwelling pleural catheter in patients with trapped lung due to malignant pleural mesothelioma designed to address recruitment and randomisation uncertainties and sample size requirements for a phase III trial.

Introduction: One of the most debilitating symptoms of malignant pleural mesothelioma (MPM) is dyspnoea caused by pleural effusion. MPM can be complicated by the presence of tumour on the visceral pleura preventing the lung from re-expanding, known as trapped lung (TL). There is currently no consensus on the best way to manage TL. One approach is insertion of an indwelling pleural catheter (IPC) under local anaesthesia. Another is video-assisted thoracoscopic partial pleurectomy/decortication (VAT-PD). Performed under general anaesthesia, VAT-PD permits surgical removal of the rind of tumour from the visceral pleura thereby allowing the lung to fully re-expand. Methods and analysis: MesoTRAP is a feasibility study that includes a pilot multicentre, randomised controlled clinical trial comparing VAT-PD with IPC in patients with TL and pleural effusion due to MPM. The primary objective is to measure the SD of visual analogue scale scores for dyspnoea following randomisation and examine the patterns of change over time in each treatment group. Secondary objectives include documenting survival and adverse events, estimating the incidence and prevalence of TL in patients with MPM, examining completion of alternative forms of data capture for economic evaluation and determining the ability to randomise 38 patients in 18 months. Ethics and dissemination: This study was approved by the East of England-Cambridge Central Research Ethics Committee and the Health Research Authority (reference number 16/EE/0370). We aim to publish the outputs of this work in international peer-reviewed journals compliant with an Open Access policy. Trial registration: NCT03412357.

Mini-Stern Trial: A randomized trial comparing mini-sternotomy to full median sternotomy for aortic valve replacement.

OBJECTIVE: Aortic valve replacement (AVR) can be performed either through full median sternotomy (FS) or upper mini-sternotomy (MS). The Mini-Stern trial aimed to establish whether MS leads to quicker postoperative recovery and shorter hospital stay after first-time isolated AVR. METHODS: This pragmatic, open-label, parallel randomized controlled trial (RCT) compared MS with FS for first-time isolated AVR in 2 United Kingdom National Health Service hospitals. Primary endpoints were duration of postoperative hospital stay and the time to fitness for discharge from hospital after AVR, analyzed in the intent-to-treat population. RESULTS: In this RCT, 222 patients were recruited and randomized (n = 118 in the MS group; n = 104 in the FS group). Compared with the FS group, the MS group had a longer hospital length of stay (mean, 9.5 days vs 8.6 days) and took longer to achieve fitness for discharge home (mean, 8.5 days vs 7.5 days). Adjusting for valve type, sex, and surgeon, hazard ratios (HRs) from Cox models did not show a statistically significant effect of MS (relative to FS) on either hospital stay (HR, 0.874; 95% confidence interval [CI], 0.668-1.143; P = .3246) or time to fitness for discharge (HR, 0.907; 95% CI, 0.688-1.197; P value = .4914). During a mean follow-up of 760 days (745 days for the MS group and 777 days for the FS group), 12 patients (10%) in the MS group and 7 patients (7%) in the FS group died (HR, 1.871; 95% CI, 0.723-4.844; P = .1966). Average extra cost for MS was £1714 during the first 12 months after AVR. CONCLUSIONS: Compared with FS for AVR, MS did not result in shorter hospital stay, faster recovery, or improved survival and was not cost-effective. The MS approach is not superior to FS for performing AVR.

Does the "Weekend Effect" for Postoperative Mortality Stand Up to Scrutiny? Association for Cardiothoracic Anesthesia and Critical Care Cohort Study of 110,728 Cardiac Surgical Patients.

OBJECTIVE: Ongoing debate focuses on whether patients admitted to the hospital on weekends have higher mortality than those admitted on weekdays. Whether this apparent "weekend effect" reflects differing patient risk, care quality differences, or inadequate adjustment for risk during analysis remains unclear. This study aimed to examine the existence of a "weekend effect" for risk-adjusted in-hospital mortality after cardiac surgery. DESIGN: Retrospective analysis of prospectively collected cardiac registry data. SETTING: Ten UK specialist cardiac centers. PARTICIPANTS: A total of 110,728 cases, undertaken by 127 consultant surgeons and 190 consultant anesthetists between April 2002 and March 2012. INTERVENTIONS: Major risk-stratified cardiac surgical operations. MEASUREMENTS AND MAIN RESULTS: Crude in-hospital mortality rate was 3.1%. Multilevel multivariable models were employed to estimate the effect of operative day on in-hospital mortality, adjusting for center, surgeon, anesthetist, patient risk, and procedure priority. Weekend elective cases had significantly lower mortality risk compared to Monday elective cases (odds ratio [OR] 0.64, 95% confidence interval [CI] 0.42, 0.96) following risk adjustment by the logistic European System for Cardiac Operative Risk Evaluation (EuroSCORE) and procedure priority; differences between weekend and Monday for urgent and emergency/salvage cases were not significant (OR 1.12, 95% CI 0.73, 1.72, and 1.07, 95% CI 0.79, 1.45 respectively). Considering only the logistic EuroSCORE but not procedure priority yielded 29% higher odds of death for weekend cases compared to Monday operations (OR 1.29, 95% CI 1.08, 1.54). CONCLUSIONS: This study suggests that undergoing cardiac surgery during the weekend does not affect negatively patient survival, and highlights the importance of comprehensive risk adjustment to avoid detecting spurious "weekend effects."