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Background: Early cancer recurrence after oesophagectomy is a common problem, with an incidence of 20–30 per cent despite the widespread use of neoadjuvant treatment. Quantification of this risk is difficult and existing models perform poorly. This study aimed to develop a predictive model for early recurrence after surgery for oesophageal adenocarcinoma using a large multinational cohort and machine learning approaches. Methods: Consecutive patients who underwent oesophagectomy for adenocarcinoma and had neoadjuvant treatment in one Dutch and six UK oesophagogastric units were analysed. Using clinical characteristics and postoperative histopathology, models were generated using elastic net regression (ELR) and the machine learning methods random forest (RF) and extreme gradient boosting (XGB). Finally, a combined (ensemble) model of these was generated. The relative importance of factors to outcome was calculated as a percentage contribution to the model. Results: A total of 812 patients were included. The recurrence rate at less than 1 year was 29·1 per cent. All of the models demonstrated good discrimination. Internally validated areas under the receiver operating characteristic (ROC) curve (AUCs) were similar, with the ensemble model performing best (AUC 0·791 for ELR, 0·801 for RF, 0·804 for XGB, 0·805 for ensemble). Performance was similar when internal–external validation was used (validation across sites, AUC 0·804 for ensemble). In the final model, the most important variables were number of positive lymph nodes (25·7 per cent) and lymphovascular invasion (16·9 per cent). Conclusion: The model derived using machine learning approaches and an international data set provided excellent performance in quantifying the risk of early recurrence after surgery, and will be useful in prognostication for clinicians and patients. [ABSTRACT FROM AUTHOR]

Complications are frequent after oesophagectomy, and there is evidence these adversely impact long-term prognosis. However, the effect of multiple complications, and the absolute magnitude of effect on survival is unclear. This study aimed to examine these effects in a single high-volume UK unit. Patients undergoing oesophagectomy for cancer and who survived to 90 days post-oesophagectomy were analysed. Complications were graded according to the Clavien-Dindo (CD) classification and the Comprehensive Complication Index (CCI). The effect and magnitude of effect of complications on survival were assessed using multivariable cox regression and the risk-adjusted population attributable fraction. In total, 380 patients were included. Complications occurred in 251 (66.1%). Suffering ≥3 complications (HR 1.89, 95%CI 1.13–3.16, p = 0.015) or an unplanned escalation in care (HR 2.22, 95%CI 1.43–3.45, p < 0.001) significantly reduced survival whereas pulmonary complications and anastomotic leak did not. Patients with a CCI>30 had worse overall survival (HR 1.91, 95%CI 1.32–2.76, p < 0.001) and CCI>30 due to multiple minor complications gave a worse prognosis compared to CCI>30 due to major complications (HR 2.44, 95%CI 1.14–5.20, p = 0.022). An estimated 9.1% (95%CI 3.4–14.4%) of deaths at 5 years were attributable to a CCI>30. Long-term survival following oesophagectomy for cancer is significantly affected by complications and the cumulative effect of multiple complications. Interestingly, multiple minor complications had a worse effect on survival than major complications. The absolute magnitude of effect is substantial: minimising all types of postoperative complications could have significant benefit to overall outcomes. [ABSTRACT FROM AUTHOR]

Objectives: In May 2001, a maximum exposure limit (MEL) for flour dust was set in the UK at 10 mg/m3 [8 h time-weighted average (TWA)] with a short-term exposure limit (STEL) of 30 mg/m3 (15 min reference period). The purpose of this study was to produce a benchmarking baseline of current control measures and exposure levels, in addition to assessing the provision of training and the knowledge of the UK regulations amongst the bakeries.Methods: A total of 208 long-term personal inhalable dust samples (8 h TWA) were collected from workers in 55 bakeries (covering a wide range of industry types and sizes) between October 2002 and December 2003 in England, Wales and Scotland. Standardized occupational hygiene reports were produced for each establishment to provide information about the site (such as the size of the bakery) and the control measures employed (including ventilation, good working practices, knowledge of UK regulations and the extent of training provided).Results: Median inhalable dust exposure (8 h TWA) for the bakery workers was 3.7 mg/m3 (75th percentile at 7.7 mg/m3) and 17% of the dust results exceeded the MEL. Although information about the MEL has been available in the trade press and through recognised trade associations, only 27% of the bakeries were aware of the MEL and STEL. Mixed model regression analysis suggested that determinants of higher exposure included the job category (particularly weighing/sieving or mixing), medium to large bakery size (50 or more employees) and bakeries being located in Scotland. However, having an appointed safety representative was associated with lower exposure.Conclusions: The conclusions derived here are based upon the use of a statistical model, but clearly, if bakeries and individuals employ good working practices, with correct use of local exhaust ventilation, they should be able to comply with the MEL. [ABSTRACT FROM AUTHOR]

Autozygosity is associated with rare Mendelian disorders and clinically relevant quantitative traits. We investigated associations between the fraction of the genome in runs of homozygosity (F ROH ) and common diseases in Genes & Health (n = 23,978 British South Asians), UK Biobank (n = 397,184), and 23andMe. We show that restricting analysis to offspring of first cousins is an effective way of reducing confounding due to social/environmental correlates of F ROH . Within this group in G&H+UK Biobank, we found experiment-wide significant associations between F ROH and twelve common diseases. We replicated associations with type 2 diabetes (T2D) and post-traumatic stress disorder via within-sibling analysis in 23andMe (median n = 480,282). We estimated that autozygosity due to consanguinity accounts for 5%-18% of T2D cases among British Pakistanis. Our work highlights the possibility of widespread non-additive genetic effects on common diseases and has important implications for global populations with high rates of consanguinity., Competing Interests: Declaration of interests J.O. and members of the 23andMe Research Team are employed by and hold stock or stock options in 23andMe, Inc. H.C.M. is a member of Cell’s advisory board. D.A.v.H., S.F., and H.C.M. have received salary contributions via the Genes & Health Industry Consortium of AstraZeneca PLC, Bristol-Myers Squibb Company, GlaxoSmithKline Research and Development Limited, Maze Therapeutics Inc., Merck Sharp & Dohme LLC, Novo Nordisk A/S, Pfizer Inc., and Takeda Development Centre Americas Inc., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objectives: To derive and validate risk prediction algorithms to estimate the risk of covid-19 related mortality and hospital admission in UK adults after one or two doses of covid-19 vaccination., Design: Prospective, population based cohort study using the QResearch database linked to data on covid-19 vaccination, SARS-CoV-2 results, hospital admissions, systemic anticancer treatment, radiotherapy, and the national death and cancer registries., Settings: Adults aged 19-100 years with one or two doses of covid-19 vaccination between 8 December 2020 and 15 June 2021., Main Outcome Measures: Primary outcome was covid-19 related death. Secondary outcome was covid-19 related hospital admission. Outcomes were assessed from 14 days after each vaccination dose. Models were fitted in the derivation cohort to derive risk equations using a range of predictor variables. Performance was evaluated in a separate validation cohort of general practices., Results: Of 6 952 440 vaccinated patients in the derivation cohort, 5 150 310 (74.1%) had two vaccine doses. Of 2031 covid-19 deaths and 1929 covid-19 hospital admissions, 81 deaths (4.0%) and 71 admissions (3.7%) occurred 14 days or more after the second vaccine dose. The risk algorithms included age, sex, ethnic origin, deprivation, body mass index, a range of comorbidities, and SARS-CoV-2 infection rate. Incidence of covid-19 mortality increased with age and deprivation, male sex, and Indian and Pakistani ethnic origin. Cause specific hazard ratios were highest for patients with Down's syndrome (12.7-fold increase), kidney transplantation (8.1-fold), sickle cell disease (7.7-fold), care home residency (4.1-fold), chemotherapy (4.3-fold), HIV/AIDS (3.3-fold), liver cirrhosis (3.0-fold), neurological conditions (2.6-fold), recent bone marrow transplantation or a solid organ transplantation ever (2.5-fold), dementia (2.2-fold), and Parkinson's disease (2.2-fold). Other conditions with increased risk (ranging from 1.2-fold to 2.0-fold increases) included chronic kidney disease, blood cancer, epilepsy, chronic obstructive pulmonary disease, coronary heart disease, stroke, atrial fibrillation, heart failure, thromboembolism, peripheral vascular disease, and type 2 diabetes. A similar pattern of associations was seen for covid-19 related hospital admissions. No evidence indicated that associations differed after the second dose, although absolute risks were reduced. The risk algorithm explained 74.1% (95% confidence interval 71.1% to 77.0%) of the variation in time to covid-19 death in the validation cohort. Discrimination was high, with a D statistic of 3.46 (95% confidence interval 3.19 to 3.73) and C statistic of 92.5. Performance was similar after each vaccine dose. In the top 5% of patients with the highest predicted covid-19 mortality risk, sensitivity for identifying covid-19 deaths within 70 days was 78.7%., Conclusion: This population based risk algorithm performed well showing high levels of discrimination for identifying those patients at highest risk of covid-19 related death and hospital admission after vaccination., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: support from the NIHR for the submitted work; JH-C reports grants from NIHR Biomedical Research Centre, Oxford, grants from John Fell Oxford University Press Research Fund, grants from Cancer Research UK, through the Cancer Research UK Oxford Centre, grants from the Oxford Wellcome Institutional Strategic Support Fund and other research councils, during the conduct of the study; JH-C is an unpaid director of QResearch, a not-for-profit organisation that is a partnership between the University of Oxford and EMIS Health, which supplied the QResearch database used for this work; JH-C is a founder and shareholder of ClinRisk and was its medical director until 31 May 2019 (ClinRisk produces open and closed source software to implement clinical risk algorithms (outside this work) into clinical computer systems); JH-C is chair of the NERVTAG risk stratification subgroup and a member of SAGE covid-19 groups and the NHS group advising on prioritisation of use of monoclonal antibodies in covid-19 infection; CACC reports receiving personal fees from ClinRisk outside this work, and is a member of the NERVTAG risk stratification subgroup; KK is supported by the NIHR Applied Research Collaboration-East Midlands and the Leicester BRC and is a member of SAGE; RHK was supported by a UKRI Future Leaders Fellowship (MR/S017968/1); KD-O was supported by a grant from the Alan Turing Institute Health Programme (EP/T001569/1); AS is a member of the Scottish Government Chief Medical Officer’s covid-19 advisory group and a member of AstraZeneca’s thrombotic thrombocytopenic advisory group (both roles are unremunerated); RAL is a member of the Welsh government covid-19 technical advisory group (unrenumerated); MGS reports grants from Department of Health and Social Care NIHR UK, grants from the UK Medical Research Council, grants from Health Protection Research Unit in Emerging and Zoonotic Infections, University of Liverpool, during the conduct of the study, and other funds from Integrum Scientific, Greensboro, NC, USA, outside the submitted work; MGS is a member of NERVTAG and attends SAGE covid-19; AH is a member of NERVTAG and the NHS group advising on prioritisation of use of monoclonal antibodies in covid-19 infection; JV is national clinical director for diabetes and obesity at NHS England and Improvement; FK is a member of the Northern Ireland Chief Medical Officer’s pandemic modelling group and strategic intelligence group; JSN-V-T is seconded to the Department of Health and Social Care, England. The views expressed in this manuscript are those of the authors and not necessarily those of Department of Health and Social Care or the UK government., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: There are a variety of surgical and endoscopic interventions available to treat gastroesophageal reflux disease. There is, however, no consensus on which approach is best.The aim of this national audit is to describe the current variation in the UK clinical practice in relation to anti-reflux surgery (ARS) and to report adherence to available clinical guidelines., Methods: This national audit will be conducted at centers across the UK using the secure online web platform ALEA. The study will comprise two parts: a registration questionnaire and a prospective multicenter audit of ARS. All participating centers will be required to complete the registration questionnaire comprising details regarding pre-, peri-, and post-operative care pathways and whether or not these are standardized within each center. Following this, a 12-month multicenter prospective audit will be undertaken to capture data including patient demographics, predominant symptoms, preoperative investigations, surgery indication, intraoperative details, and postoperative outcomes within the first 90 days.Local teams will retain access to their own data to facilitate local quality improvement. The full dataset will be reported at national and international scientific congresses and will contribute to peer-reviewed publications and national quality improvement initiatives., Conclusions: This study will identify and explore variation in the processes and outcomes following ARS within the UK using a collaborative cohort methodology. The results generated by this audit will facilitate local and national quality improvement initiatives and generate new possibilities for future research in anti-reflux interventions., (© The Author(s) 2021. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus.)

The COVID-19 pandemic has been a disruptive event for cancer patients, especially those with haematological malignancies (HM). They may experience a more severe clinical course due to impaired immune responses. This multi-center retrospective UK audit identified cancer patients who had SARS-CoV-2 infection between 1 March and 10 June 2020 and collected data pertaining to cancer history, COVID-19 presentation and outcomes. In total, 179 patients were identified with a median age of 72 (IQR 61, 81) and follow-up of 44 days (IQR 42, 45). Forty-one percent were female and the overall mortality was 37%. Twenty-nine percent had HM and of these, those treated with chemotherapy in the preceding 28 days to COVID-19 diagnosis had worse outcome compared with solid malignancy (SM): 62% versus 19% died [HR 8.33 (95% CI, 2.56-25), p  < 0.001]. Definite or probable nosocomial SARS-CoV-2 transmission accounted for 16% of cases and was associated with increased risk of death (HR 2.47, 95% CI 1.43-4.29, p  = 0.001). Patients with haematological malignancies and those who acquire nosocomial transmission are at increased risk of death. Therefore, there is an urgent need to reassess shielding advice, reinforce stringent infection control, and ensure regular patient and staff testing to prevent nosocomial transmission.

We calculate the average sales of new antibiotics during their first 8 years on the market. The discounted net present value is only $240 m in total per antibiotic, well below costs of supplying these products. The reliance on the US for sales is striking: the US market accounts for 84% of sales during the first 8 years. These facts clarify the need for additional revenues, especially from other countries, to support incentives for the development of new antibiotics. Market entry rewards may be of particular value.

Academic output is just one aspect of a successful career as a plastic surgeon. However, for those with a strong interest in academia, the academic output of a department will likely be a key factor when deciding how to rank jobs. The aim of this study was to quantify and rank the academic output of plastic surgery units across the UK and Ireland. The Institute for Scientific Information (ISI) Web of Science Bibliometric analysis tool was used to collate cumulative (1950-2016), 10 year (2006-2016) and 3 years (2013-2015) research output data for plastic surgery units in the UK and Ireland. Sixty-six plastic surgery units were identified. Departments were ranked for each time period according to the number of papers produced, number of citations (Nc) and h-index (a measure of the impact of scientific output). The top 3 departments for number of papers in the last 10 years were The Royal Free Hospital, London (226) Broomfield Hospital, Chelmsford (218), and Morriston Hospital and Swansea (188). The top 3 for h-number were The Royal Free Hospital (21) Wythenshawe Hospital, Manchester (18) and Morriston Hospital (17). Academic output varies across plastic surgery units in the UK and Ireland. A number of departments have consistently maintained high academic outputs across the years and will be of interest to surgeons hoping to pursue a career in academia.

Medical identification jewellery can convey vital information to emergency responders, but mistakes and ambiguity may lead to misdiagnosis and morbidity. We performed a review of relevant articles retrieved from Pubmed ® , Embase ® and Scopus ® and Google UK Inc. to investigate the commercial availability and issuance of these products. From 84 identified studies, we shortlisted 74 for review. The Google search retrieved 1,090,000 results within 0.57 s (January 2017). We explored 32 websites selling medical alert jewellery in the first five pages of these results. We found that patients themselves are currently responsible for the engraved wording on medical alert jewellery, with no mandatory physician checks. The accuracy and appropriateness of this information may thus vary. In the absence of national guidance in the UK, we suggest that there should be a list of specific indications warranting their use, a requirement for regular review of information, and clarity around the level of physician input into the engraving chosen. We discuss the potential benefits vs. risks of wearing medical alert jewellery and clarify the limitations of medical teams' responsibilities in relation to patients found to be wearing them., (© 2017 The Association of Anaesthetists of Great Britain and Ireland.)

Objectives: The objective of this study was to examine determinants of excess coronary artery disease risk in UK South Asians, more prevalent in this population than UK Caucasians, by examining differences in risk factors, vascular function, and endothelial progenitor cells (EPCs)., Methods and Results: 24 South Asian and 25 Caucasian healthy age-matched nonsmoking men were studied. Vascular function was assessed by flow-mediated and GTN brachial artery dilatation and blood flow responses to infusion of ACh, SNP, and L-NMMA. EPC number and function were measured by flow cytometry (CD34, CD133, and KDR positive cells), and CFU/migration assays. Traditional risk factors and anthropometric measurements were similar in the groups. South Asians had higher fasting insulin levels (6.01 versus 3.62 microU/mL; P = 0.02). South Asians had lower FMD (6.9 versus 8.5%; P = 0.003), L-NMMA response (0.8 versus 1.3 mL/min/100 mL; P = 0.03), mean SNP response (9.5+/-0.6 versus 11.6+/-0.6; P = 0.02), EPC number (0.046+/-0.005% versus 0.085+/-0.009%; P = < 0.001), and CFU ability (CFU 4.29+/-1.57 versus 18.86+/-4.00; P = 0.005). EPC number was the strongest predictor of FMD. Ethnicity was the strongest predictor of EPC number., Conclusions: Healthy South Asian men are more insulin resistant, and demonstrate endothelial dysfunction and reduced EPC number and function compared with Caucasians. These abnormalities may contribute to their increased CAD risk.