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Background The annual influenza vaccination is recommended for all front-line healthcare workers in the UK and is a crucial way of reducing mortality for vulnerable patient groups. However, to date the UK government has never explicitly monitored influenza vaccine uptake in medical students. This is important to ascertain, as students regularly move between clinical areas and are both a perfect vector for the spread of influenza and at an increased risk of contracting influenza themselves. Aims This service evaluation was designed to evaluate the effectiveness of an influenza vaccination programme in one UK medical school and make recommendations to increase vaccination rates in the future. Methods This service evaluation collected data about medical student uptake of influenza vaccination in one UK medical school. Two hundred and fifty-one students at different course stages completed questionnaires, answering questions on vaccination status and Likert-scale 'belief' questions to assess the subjective reasons behind vaccine refusal. Results There was a substantial difference between year group cohorts (~20%), with significantly higher vaccination rates in the preclinical year group. Two significant negative predictors of vaccination were found (P < 0.001), related to scepticism over the effectiveness of the vaccine and lack of convenient access to the vaccination. Results indicated that integrating information about the influenza vaccine into the curriculum would reduce lack of knowledge over the efficacy of the vaccine. The centralization of vaccination programmes at mandatory university-based learning events would mitigate against the problem of diversity of vaccination locations and lack of central accountability. Conclusions The results of this service evaluation provide significant predictors of vaccination status for medical students and potential occupational health interventions to improve vaccine uptake in this group. [ABSTRACT FROM AUTHOR]

In the last decade, research in transplant medicine has focused on developing interventions in the management of the deceased organ donor to improve the quality and quantity of transplantable organs. Despite the promise of interventional donor research, there remain debates about the ethics of this research, specifically regarding gaining research consent. Here, we examine the concerns and ambiguities around consent for interventional donor research, which incorporate questions about who should consent for interventional donor research and what people are being asked to consent for. We highlight the US and UK policy responses to these concerns and argue that, whereas guidance in this area has done much to clarify these ambiguities, there is little consideration of the nature, practicalities and context around consent in this area, particularly regarding organ donors and their families. We review wider studies of consent in critical care research and social science studies of consent in medical research, to gain a broader view of consent in this area as a relational and contextual process. We contend a lack of consideration has been given to: what it might mean to consent to interventional donor research; how families, patients and health professionals might experience providing and seeking this consent; who is best placed to have these discussions; and the socio-institutional contexts affecting these processes. Further, empirical research is required to establish an ethical and sensitive model for consent in interventional donor research, ensuring the principles enshrined in research ethics are met and public trust in organ donation is maintained. [ABSTRACT FROM AUTHOR]

Background: The Hall technique for placement of preformed metal crowns is widely used in the UK for the management of decayed primary molar teeth. The creation of space is achieved by the placement of orthodontic separators adjacent to the tooth requiring restoration. Highlighting the first reported case of an abrasion caused by dental floss, this communication describes the clinical findings of an 8-year-old patient following placement of orthodontic separators. Case report: An 8-year old boy attended the University Dental Hospital of Manchester for placement of orthodontic separators prior to restoration URE, ULE, LLE, and LRE with preformed metal crowns using the hall technique. The following week he presented with a 2cm abrasion to his right cheek, which had been caused by dental floss used in placement of the orthodontic separators. Follow up: Conservative advice was given and the lesion had resolved completely at a 2-week review. Conclusion: This case is a timely reminder of the importance of adequate lip retraction and soft tissue management during placement of orthodontic separators. [ABSTRACT FROM AUTHOR]

Abstract: Background: This study aims to characterise the injuries and surgical management of British servicemen sustaining bilateral lower limb amputations. Methods: The UK Military Trauma Registry was searched for all cases of primary bilateral lower limb amputation sustained between March 2004 and March 2010. Amputations were excluded if they occurred more than 7 days after injury or if they were at the ankle or more distal. Results: There were 1694 UK military patients injured or killed during this six-year study period. Forty-three of these (2.8%) were casualties with bilateral lower limb amputations. All casualties were men with a mean age of 25.1 years (SD 4.3): all were injured in Afghanistan by Improvised Explosive Devices (IEDs). Six casualties were in vehicles when they were injured with the remaining 37 (80%) patrolling on foot. The mean New Injury Severity Score (NISS) was 48.2 (SD 13.2): four patients had a maximum score of 75. The mean TRISS probability of survival was 60% (SD 39.4), with 18 having a survival probability of less than 50% i.e. unexpected survivors. The most common amputation pattern was bilateral trans-femoral (TF) amputations, which was seen in 25 patients (58%). Nine patients also lost an upper limb (triple amputation): no patients survived loss of all four limbs. In retained upper limbs extensive injuries to the hands and forearms were common, including loss of digits. Six patients (14%) sustained an open pelvic fracture. Perineal/genital injury was a feature in 19 (44%) patients, ranging from unilateral orchidectomy to loss of genitalia and permanent requirement for colostomy and urostomy. The mean requirement for blood products was 66 units (SD 41.7). The maximum transfusion was 12 units of platelets, 94 packed red cells, 8 cryoprecipitate, 76 units of fresh frozen plasma and 3 units of fresh whole blood, a total of 193 units of blood products. Conclusions: Our findings detail the severe nature of these injuries together with the massive surgical and resuscitative efforts required to firstly keep patients alive and secondly reconstruct and prepare them for rehabilitation. [Copyright &y& Elsevier]

In the United Kingdom, the prevalence of children and young people (CYP) accessing acute paediatric inpatient care with mental health problems is increasing, with self-harm and eating disorders particularly prevalent. This study evaluated CYP experiences of being in receipt of acute paediatric inpatient care following either self-harm or crisis stemming from an eating disorder to inform domains for a person-centred outcome measure (PCOM). A series of stakeholder engagement events were conducted between April and July 2015 where creative approaches were used to explore stakeholder experiences of care and to identify outcome domains that were subsequently prioritised using a Nominal Group Technique. Data were analysed using inductive thematic approach, with significance scores calculated for domain statements. Ninety-six stakeholders (15 CYP, eight parents and carers, and 73 professionals) participated. Findings showed five priority PCOM domains: privacy and surveillance; holistic care; making choices, appropriate communication; working together to achieve care goals; and respect and empowerment. This single centre evaluation highlights the need for a PCOM to be developed for this patient group that comprehensively reflects stakeholders' expectations in order to inform improvements to quality of acute paediatric care., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr Joseph Manning is currently funded through HEE NIHR ICA Clinical Lectureship and therefore the views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. Dr Joanne Cooper is employed part-time by NHS England and NHS Improvement; therefore, the views expressed are those of the author and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care.

Aims: To evaluate the relationship between neuroticism personality traits and cardiovascular magnetic resonance (CMR) measures of cardiac morphology and function, considering potential differential associations in men and women., Methods and Results: The analysis includes 36 309 UK Biobank participants (average age = 63.9 ± 7.7 years; 47.8% men) with CMR available and neuroticism score assessed by the 12-item Eysenck Personality Questionnaire-Revised Short Form. CMR scans were performed on 1.5 Tesla scanners (MAGNETOM Aera, Siemens Healthcare, Erlangen, Germany) according to pre-defined protocols and analysed using automated pipelines. We considered measures of left ventricular (LV) and right ventricular (RV) structure and function, and indicators of arterial compliance. Multivariable linear regression was used to estimate association of neuroticism score with individual CMR metrics, with adjustment for age, sex, obesity, deprivation, smoking, diabetes, hypertension, hypercholesterolaemia, alcohol use, exercise, and education. Higher neuroticism scores were associated with smaller LV and RV end-diastolic volumes, lower LV mass, greater concentricity (higher LV mass to volume ratio), and higher native T1. Greater neuroticism was also linked to poorer LV and RV function (lower stroke volumes) and greater arterial stiffness. In sex-stratified analyses, the relationships between neuroticism and LV stroke volume, concentricity, and arterial stiffness were attenuated in women. In men, association (with exception of native T1) remained robust., Conclusion: Greater tendency towards neuroticism personality traits is linked to smaller, poorer functioning ventricles with lower LV mass, higher myocardial fibrosis, and higher arterial stiffness. These relationships are independent of traditional vascular risk factors and are more robust in men than women., Competing Interests: Conflict of interest: S.E.P. provides consultancy to Cardiovascular Imaging Inc, Calgary, Alberta, Canada. The remaining authors have no disclosures., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Sleep duration and chronotype have been associated with increased morbidity and mortality. We assessed for associations between sleep duration and chronotype on cardiac structure and function. UK Biobank participants with CMR data and without known cardiovascular disease were included. Self-reported sleep duration was categorized as short (<7 h/d), normal (7-9 h/d) and long (>9 h/d). Self-reported chronotype was categories as "definitely morning" or "definitely evening." Analysis included 3903 middle-aged adults: 929 short, 2924 normal and 50 long sleepers; with 966 definitely-morning and 355 definitely-evening chronotypes. Long sleep was independently associated with lower left ventricular (LV) mass (-4.8%, P = 0.035), left atrial maximum volume (-8.1%, P = 0.041) and right ventricular (RV) end-diastolic volume (-4.8%, P = 0.038) compared to those with normal sleep duration. Evening chronotype was independently associated with lower LV end-diastolic volume (-2.4%, P = 0.021), RV end-diastolic volume (-3.6%, P = 0.0006), RV end systolic volume (-5.1%, P = 0.0009), RV stroke volume (RVSV -2.7%, P = 0.033), right atrial maximal volume (-4.3%, P = 0.011) and emptying fraction (+1.3%, P = 0.047) compared to morning chronotype. Sex interactions existed for sleep duration and chronotype and age interaction for chronotype even after considering potential confounders. In conclusion, longer sleep duration was independently associated with smaller LV mass, left atrial volume and RV volume. Evening chronotype was independently associated with smaller LV and RV and reduced RV function compared to morning chronotype. Sex interactions exist with cardiac remodeling most evident in males with long sleep duration and evening chronotype. Recommendations for sleep chronotype and duration may need to be individualized based on sex., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: To evaluate incident cardiovascular outcomes and imaging phenotypes in UK Biobank participants with previous cancer., Methods: Cancer and cardiovascular disease (CVD) diagnoses were ascertained using health record linkage. Participants with cancer history (breast, lung, prostate, colorectal, uterus, haematological) were propensity matched on vascular risk factors to non-cancer controls. Competing risk regression was used to calculate subdistribution HRs (SHRs) for associations of cancer history with incident CVD (ischaemic heart disease (IHD), non-ischaemic cardiomyopathy (NICM), heart failure (HF), atrial fibrillation/flutter, stroke, pericarditis, venous thromboembolism (VTE)) and mortality outcomes (any CVD, IHD, HF/NICM, stroke, hypertensive disease) over 11.8±1.7 years of prospective follow-up. Linear regression was used to assess associations of cancer history with left ventricular (LV) and left atrial metrics., Results: We studied 18 714 participants (67% women, age: 62 (IQR: 57-66) years, 97% white ethnicities) with cancer history, including 1354 individuals with cardiovascular magnetic resonance. Participants with cancer had high burden of vascular risk factors and prevalent CVDs. Haematological cancer was associated with increased risk of all incident CVDs considered (SHRs: 1.92-3.56), larger chamber volumes, lower ejection fractions, and poorer LV strain. Breast cancer was associated with increased risk of selected CVDs (NICM, HF, pericarditis and VTE; SHRs: 1.34-2.03), HF/NICM death, hypertensive disease death, lower LV ejection fraction, and lower LV global function index. Lung cancer was associated with increased risk of pericarditis, HF, and CVD death. Prostate cancer was linked to increased VTE risk., Conclusions: Cancer history is linked to increased risk of incident CVDs and adverse cardiac remodelling independent of shared vascular risk factors., Competing Interests: Competing interests: SEP provides consultancy to Cardiovascular Imaging Inc, Calgary, Alberta, Canada. The remaining authors have nothing to disclose., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Objective: To examine association of COVID-19 with incident cardiovascular events in 17 871 UK Biobank cases between March 2020 and 2021., Methods: COVID-19 cases were defined using health record linkage. Each case was propensity score-matched to two uninfected controls on age, sex, deprivation, body mass index, ethnicity, diabetes, prevalent ischaemic heart disease (IHD), smoking, hypertension and high cholesterol. We included the following incident outcomes: myocardial infarction, stroke, heart failure, atrial fibrillation, venous thromboembolism (VTE), pericarditis, all-cause death, cardiovascular death, IHD death. Cox proportional hazards regression was used to estimate associations of COVID-19 with each outcome over an average of 141 days (range 32-395) of prospective follow-up., Results: Non-hospitalised cases (n=14 304) had increased risk of incident VTE (HR 2.74 (95% CI 1.38 to 5.45), p=0.004) and death (HR 10.23 (95% CI 7.63 to 13.70), p<0.0001). Individuals with primary COVID-19 hospitalisation (n=2701) had increased risk of all outcomes considered. The largest effect sizes were with VTE (HR 27.6 (95% CI 14.5 to 52.3); p<0.0001), heart failure (HR 21.6 (95% CI 10.9 to 42.9); p<0.0001) and stroke (HR 17.5 (95% CI 5.26 to 57.9); p<0.0001). Those hospitalised with COVID-19 as a secondary diagnosis (n=866) had similarly increased cardiovascular risk. The associated risks were greatest in the first 30 days after infection but remained higher than controls even after this period., Conclusions: Individuals hospitalised with COVID-19 have increased risk of incident cardiovascular events across a range of disease and mortality outcomes. The risk of most events is highest in the early postinfection period. Individuals not requiring hospitalisation have increased risk of VTE, but not of other cardiovascular-specific outcomes., Competing Interests: Competing interests: SEP provides consultancy to Cardiovascular Imaging, Calgary, Alberta, Canada. BR has consulted for Axcella Therapeutics. The remaining authors have nothing to disclose., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Background and Aims: The United Kingdom (UK) Psychoactive Substances Act (PSA), implemented on the 26 th  May 2016, made the production, supply and sale of all non-exempted psychoactive substances illegal. The aim of this study was to measure trends in hospital presentations for severe toxicity following analytically confirmed synthetic cannabinoid receptor agonist (SCRA) exposure before and after implementation of the PSA., Design: Observational study., Setting: Thirty-four hospitals across the UK participating in the Identification of Novel Psychoactive Substances (IONA) study., Participants: A total of 627 (79.9% male) consenting individuals who presented to participating hospitals between July 2015 and December 2019 with severe acute toxicity and suspected novel psychoactive substances exposure., Measurements: Toxicological analyses of patient samples were conducted using liquid-chromatography tandem mass-spectrometry. Time-series analysis was conducted on the monthly number of patients with and without analytically confirmed SCRA exposure using Poisson segmented regression., Findings: SCRAs were detected in 35.7% (n = 224) of patients. After adjusting for seasonality and the number of active sites, models showed no clear evidence of an upward or downward trend in the number of SCRA exposure cases in the period before (incidence rate ratio [IRR], 1.12; 95% CI, 0.99-1.26; P = 0.068) or after (IRR, 0.97; 95% CI, 0.94-1.01; P = 0.202) the implementation of the PSA. There was also no clear evidence of an upward or downward trend in non-SCRA exposure cases before (IRR, 1.12; 95% CI, 0.98-1.27; P = 0.105) or after (IRR, 1.01; 95% CI, 0.98-1.04; P = 0.478) implementation of the PSA., Conclusions: There is no clear evidence of an upward or downward trend in the number of patients presenting to UK hospitals with severe acute toxicity following analytically confirmed synthetic cannabinoid receptor agonist exposure since the implementation of the Psychoactive Substances Act., (© 2022 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.)

Background: Mitral annular disjunction is the atrial displacement of the mural mitral valve leaflet hinge point within the atrioventricular junction. Said to be associated with malignant ventricular arrhythmias and sudden death, its prevalence in the general population is not known., Objectives: The purpose of this study was to assess the frequency of occurrence and extent of mitral annular disjunction in a large population cohort., Methods: The authors assessed the cardiac magnetic resonance (CMR) images in 2,646 Caucasian subjects enrolled in the UK Biobank imaging study, measuring the length of disjunction at 4 points around the mitral annulus, assessing for presence of prolapse or billowing of the leaflets, and for curling motion of the inferolateral left ventricular wall., Results: From 2,607 included participants, the authors found disjunction in 1,990 (76%) cases, most commonly at the anterior and inferior ventricular wall. The authors found inferolateral disjunction, reported as clinically important, in 134 (5%) cases. Prolapse was more frequent in subjects with disjunction (odds ratio [OR]: 2.5; P = 0.02), with positive associations found between systolic curling and disjunction at any site (OR: 3.6; P < 0.01), and systolic curling and prolapse (OR: 71.9; P < 0.01)., Conclusions: This large-scale study shows that disjunction is a common finding when using CMR. Disjunction at the inferolateral ventricular wall, however, was rare. The authors found associations between disjunction and both prolapse and billowing of the mural mitral valve leaflet. These findings support the notion that only extensive inferolateral disjunction, when found, warrants consideration of further investigation, but disjunction elsewhere in the annulus should be considered a normal finding., Competing Interests: Funding Support and Author Disclosures This work was partly funded by the European Union’s Horizon 2020 research and innovation program under grant agreement number 825903 (euCanSHare project, Dr Petersen). Dr Petersen acknowledges support from the National Institute for Health Research (NIHR) Biomedical Research Centre at Barts, London, United Kingdom. Drs Petersen, Neubauer, and Piechnik acknowledge the British Heart Foundation, London, United Kingdom, for funding the manual analysis to create a cardiovascular magnetic resonance imaging reference standard for the UK Biobank imaging resource in 5000 CMR scans (PG/14/89/31194). This project was enabled through access to the Medical Research Council eMedLab Medical Bioinformatics infrastructure, supported by the Medical Research Council (MR/L016311/1). Dr Zugwitz acknowledges funding received from the European Society of Cardiology, Sophia Antipolis Cedex, France, in the form of an European Society of Cardiology Training Grant. Dr Neubauer acknowledges support from the Oxford NIHR Biomedical Research Centre and the Oxford British Heart Foundation Centre of Research Excellence. Dr Aung recognizes the NIHR Integrated Academic Training program, which supports his Academic Clinical Lectureship post. Drs McCracken and Neubauer are supported by the Oxford NIHR Biomedical Research Centre. Drs Petersen and Rauseo acknowledge support by the London Medical Imaging and Artificial Intelligence Centre for Value Based Healthcare (AI4VBH), which is funded from the Data to Early Diagnosis and Precision Medicine strand of the government’s Industrial Strategy Challenge Fund, managed and delivered by Innovate UK on behalf of United Kingdom Research and Innovation (UKRI). Dr Nijveldt has received research grants from Philips Volcano and Biotronik. Dr Petersen provides consultancy to Circle Cardiovascular Imaging, Inc. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Decreased renal function is a potential risk factor for dementia., Methods: This retrospective cohort study of 2.8 million adults aged ≥50 years used the IMRD-THIN database, representative of UK primary care, from January 1, 1995 to February 24, 2020. The associations between estimated glomerular filtration rate (eGFR) and urine albumin creatinine ratio (ACR) with incident all-cause dementia were analyzed using Cox regression., Results: In the eGFR cohort (n = 2,797,384), worsening renal dysfunction was associated with increased hazard of all-cause dementia, with greatest hazard at eGFR 15-30 ml/min/1.73min 2 (hazard ratio [HR] 1.26, 95% confidence interval [CI] 1.19-1.33). In the ACR cohort (n = 641,912), the hazard of dementia increased from ACR 3-30 mg/mmol (HR 1.13, 95% CI 1.10-1.15) to ACR > 30 mg/mmol (HR 1.25, 95% CI 1.18-1.33)., Discussion: Worsening eGFR and albuminuria have graded associations with the risk of dementia, which may have significant implications for the care of patients with kidney disease., (© 2021 the Alzheimer's Association.)

This ethnographic study in two socio-economically contrasting areas employed geo-ethnography, underpinned by a relational approach, to understand inequalities in gastrointestinal infections in families with young children. In our 'relatively disadvantaged' area, gastrointestinal infections spread to multiple households within a small radius, whereas in our 'relatively advantaged' area, illness was confined to one household or dispersed long distances. These differences were shaped by historical, social and economic contrasts in: housing; social networks and childcare arrangements; employment and household income. Our findings show how linking places, pathogens and people helps us understand inequalities in gastrointestinal infections and may be pertinent to other infectious diseases such as COVID-19., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: To compare the incident risk of RA in patients with type 2 diabetes mellitus (T2DM) and to explore the role of glycaemic control and associated therapeutic use in the onset of RA., Methods: This study was a retrospective cohort study using patients derived from the IQVIA Medical Research Data (IMRD-UK) database between 1995 and 2019. A total of 224 551 newly diagnosed patients with T2DM were matched to 449 101 patients without T2DM and followed up to assess their risk of RA. Further analyses investigated the effect of glycaemic control, statin use and anti-diabetic drugs on the relationship between T2DM and RA using a time-dependent Cox regression model., Results: During the study period, the incidence of RA was 8.1 and 10.6 per 10 000 person-years in the exposed and unexposed groups, respectively. The adjusted hazard ratio (aHR) was 0.73 (95% CI 0.67, 0.79). In patients who had not used statins in their lifetime, the aHR was 0.89 (95% CI 0.69, 1.14). When quantifying the effects of glycaemic control, anti-diabetic drugs and statins using time-varying analyses, there was no association with glycaemic control [aHR 1.00 (95% CI 0.99, 1.00)], use of metformin [aHR 1.00 (95% CI 0.82, 1.22)], dipeptidyl peptidase-4 inhibitors [DPP4is; aHR 0.94 (95% CI 0.71, 1.24)] and the development of RA. However, statins demonstrated a protective effect for progression of RA in those with T2DM [aHR 0.76 (95% CI 0.66, 0.88)], with evidence of a duration-response relationship., Conclusion: There is a reduced risk of RA in patients with T2DM that may be attributable to the use of statins., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Aim: To investigate how distributed leadership via the Shared Governance programme influences employee engagement, empowerment, job satisfaction and turnover intentions among direct care nursing staff in a large UK hospital., Background: Increasing turnover rates and shortages of health care staff in the UK has called for interventions to improve employee engagement and job satisfaction., Methods: 116 direct care nursing staff were sampled in a mixed-methods explanatory sequential design. A maximum variance sample of 15 participants were subsequently interviewed to gain a deeper understanding of the motivations and attitudes that influenced employee outcomes through distributed leadership., Results: Higher levels of distributed leadership predicted increased employee engagement and job satisfaction, and lower turnover intentions. Staff also felt more empowered and committed to the organisation despite some challenges experienced in implementing the Shared Governance programme., Conclusion: Distributed leadership was found to be beneficial in promoting employee engagement and empowerment, increasing job satisfaction and organisational commitment and reducing turnover intention in the UK health care setting., Implications for Nursing Management: By encouraging the practice of distributed leadership at work, health care staff can become more engaged and empowered, leading to higher rates of job retention, job satisfaction and organisational commitment., (© 2021 The Authors. Journal of Nursing Management published by John Wiley & Sons Ltd.)

Gastrointestinal infections are an important global public health issue. In the UK, one in four people experience a gastrointestinal infection each year and epidemiological research highlights inequalities in the burden of disease. Specifically, poorer children are at greater risk of infection and the consequences of illness, such as symptom severity and time off work/school, are greater for less privileged groups of all ages. Gastrointestinal infections are, however, largely 'hidden' within the home and little is known about the lived experience and practices surrounding these illnesses, how they vary across contrasting socioeconomic contexts, or how inequalities in the disease burden across socioeconomic groups might come about. This paper presents data from an ethnographic study which illuminate how socioeconomic inequalities in the physical and material management and consequences of gastrointestinal infections are generated in families with young children. The study shows how the 'work' needed to manage gastrointestinal infections is more laborious for people living in more 'disadvantaged' conditions, exacerbated by: more overcrowded homes with fewer washing and toilet facilities; inflexible employment; low household incomes; and higher likelihood of co-morbidities which can be made worse by having a gastrointestinal infection. Our findings call into question the current approach to prevention of gastrointestinal infections which tend to focus almost exclusively on individual behaviours, which are not adapted to reflect differences in socioeconomic context. Public health agencies should also consider how wider social, economic and policy contexts shape inequalities in the management and consequences of illness. Our findings are also pertinent to the COVID-19 pandemic response in the UK. They highlight how research and policy approaches to acute infectious diseases need to take into consideration the differing lived experiences of contrasting households if they wish to address (and avoid exacerbating) inequalities in the future., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Contrast-induced nephropathy (CIN), an acute kidney injury resulting from the administration of intravascular iodinated contrast media, is a significant cause of morbidity/mortality following coronary angiographic procedures in high-risk patients. Despite preventative measures intended to mitigate the risk of CIN, there remains a need for novel effective treatments. Evidence suggests that delivery of nitric oxide (NO) through chemical reduction of inorganic nitrate to NO may offer a novel therapeutic strategy to reduce CIN and thus preserve long term renal function., Design: The NITRATE-CIN trial is a single-center, randomized, double-blind placebo-controlled trial, which plans to recruit 640 patients presenting with acute coronary syndromes (ACS) who are at risk of CIN. Patients will be randomized to either inorganic nitrate therapy (capsules containing 12 mmol KNO 3 ) or placebo capsules containing potassium chloride (KCl) daily for 5 days. The primary endpoint is development of CIN using the Kidney Disease Improving Global Outcomes (KDIGO) criteria. A key secondary endpoint is renal function over a 3-month follow-up period. Additional secondary endpoints include serum renal biomarkers (e.g. neutrophil gelatinase-associated lipocalin) at 6 h, 48 h and 3 months following administration of contrast. Cost-effectiveness of inorganic nitrate therapy will also be evaluated., Summary: This study is designed to investigate the hypothesis that inorganic nitrate treatment decreases the rate of CIN as part of semi-emergent coronary angiography for ACS. Inorganic nitrate is a simple and easy to administer intervention that may prove useful in prevention of CIN in at-risk patients undergoing coronary angiographic procedures.

Objective: To identify whether active use of nonsteroidal antiinflammatory drugs (NSAIDs) increases susceptibility to developing suspected or confirmed coronavirus disease 2019 (COVID-19) compared to the use of other common analgesics., Methods: We performed a propensity score-matched cohort study with active comparators, using a large UK primary care data set. The cohort consisted of adult patients age ≥18 years with osteoarthritis (OA) who were followed up from January 30 to July 31, 2020. Patients prescribed an NSAID (excluding topical preparations) were compared to those prescribed either co-codamol (paracetamol and codeine) or co-dydramol (paracetamol and dihydrocodeine). A total of 13,202 patients prescribed NSAIDs were identified, compared to 12,457 patients prescribed the comparator drugs. The primary outcome measure was the documentation of suspected or confirmed COVID-19, and the secondary outcome measure was all-cause mortality., Results: During follow-up, the incidence rates of suspected/confirmed COVID-19 were 15.4 and 19.9 per 1,000 person-years in the NSAID-exposed group and comparator group, respectively. Adjusted hazard ratios for suspected or confirmed COVID-19 among the unmatched and propensity score-matched OA cohorts, using data from clinical consultations in primary care settings, were 0.82 (95% confidence interval [95% CI] 0.62-1.10) and 0.79 (95% CI 0.57-1.11), respectively, and adjusted hazard ratios for the risk of all-cause mortality were 0.97 (95% CI 0.75-1.27) and 0.85 (95% CI 0.61-1.20), respectively. There was no effect modification by age or sex., Conclusion: No increase in the risk of suspected or confirmed COVID-19 or mortality was observed among patients with OA in a primary care setting who were prescribed NSAIDs as compared to those who received comparator drugs. These results are reassuring and suggest that in the absence of acute illness, NSAIDs can be safely prescribed during the ongoing pandemic., (© 2020 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Background: Coronavirus disease 2019 (COVID-19) disproportionately affects older people. Observational studies suggest indolent cardiovascular involvement after recovery from acute COVID-19. However, these findings may reflect pre-existing cardiac phenotypes., Aims: We tested the association of baseline cardiovascular magnetic resonance (CMR) phenotypes with incident COVID-19., Methods: We studied UK Biobank participants with CMR imaging and COVID-19 testing. We considered left and right ventricular (LV, RV) volumes, ejection fractions, and stroke volumes, LV mass, LV strain, native T1, aortic distensibility, and arterial stiffness index. COVID-19 test results were obtained from Public Health England. Co-morbidities were ascertained from self-report and hospital episode statistics (HES). Critical care admission and death were from HES and death register records. We investigated the association of each cardiovascular measure with COVID-19 test result in multivariable logistic regression models adjusting for age, sex, ethnicity, deprivation, body mass index, smoking, diabetes, hypertension, high cholesterol, and prior myocardial infarction., Results: We studied 310 participants (n = 70 positive). Median age was 63.8 [57.5, 72.1] years; 51.0% (n = 158) were male. 78.7% (n = 244) were tested in hospital, 3.5% (n = 11) required critical care admission, and 6.1% (n = 19) died. In fully adjusted models, smaller LV/RV end-diastolic volumes, smaller LV stroke volume, and poorer global longitudinal strain were associated with significantly higher odds of COVID-19 positivity., Discussion: We demonstrate association of pre-existing adverse CMR phenotypes with greater odds of COVID-19 positivity independent of classical cardiovascular risk factors., Conclusions: Observational reports of cardiovascular involvement after COVID-19 may, at least partly, reflect pre-existing cardiac status rather than COVID-19 induced alterations.

Background: Early studies conclude patients with Covid-19 have a high risk of death, but no studies specifically explore cardiac surgery outcome. We investigate UK cardiac surgery outcomes during the early phase of the Covid-19 pandemic., Methods: This retrospective observational study included all adult patients undergoing cardiac surgery between 1st March and 30th April 2020 in nine UK centres. Data was obtained and linked locally from the National Institute for Cardiovascular Outcomes Research Adult Cardiac Surgery database, the Intensive Care National Audit and Research Centre database and local electronic systems. The anonymised datasets were analysed by the lead centre. Statistical analysis included descriptive statistics, propensity score matching (PSM), conditional logistic regression and hierarchical quantile regression., Results: Of 755 included individuals, 53 (7.0%) had Covid-19. Comparing those with and without Covid-19, those with Covid-19 had increased mortality (24.5% v 3.5%, p < 0.0001) and longer post-operative stay (11 days v 6 days, p = 0.001), both of which remained significant after PSM. Patients with a pre-operative Covid-19 diagnosis recovered in a similar way to non-Covid-19 patients. However, those with a post-operative Covid-19 diagnosis remained in hospital for an additional 5 days (12 days v 7 days, p = 0.024) and had a considerably higher mortality rate compared to those with a pre-operative diagnosis (37.1% v 0.0%, p = 0.005)., Conclusions: To mitigate against the risks of Covid-19, particularly the post-operative burden, robust and effective pre-surgery diagnosis protocols alongside effective strategies to maintain a Covid-19 free environment are needed. Dedicated cardiac surgery hubs could be valuable in achieving safe and continual delivery of cardiac surgery.

Introduction: Renin-angiotensin system (RAS) inhibitors have been postulated to influence susceptibility to Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). This study investigated whether there is an association between their prescription and the incidence of COVID-19 and all-cause mortality., Methods: We conducted a propensity-score matched cohort study comparing the incidence of COVID-19 among patients with hypertension prescribed angiotensin-converting enzyme I (ACE) inhibitors or angiotensin II type-1 receptor blockers (ARBs) to those treated with calcium channel blockers (CCBs) in a large UK-based primary care database (The Health Improvement Network). We estimated crude incidence rates for confirmed/suspected COVID-19 in each drug exposure group. We used Cox proportional hazards models to produce adjusted hazard ratios for COVID-19. We assessed all-cause mortality as a secondary outcome., Results: The incidence rate of COVID-19 among users of ACE inhibitors and CCBs was 9.3 per 1000 person-years (83 of 18,895 users [0.44%]) and 9.5 per 1000 person-years (85 of 18,895 [0.45%]), respectively. The adjusted hazard ratio was 0.92 (95% CI 0.68 to 1.26). The incidence rate among users of ARBs was 15.8 per 1000 person-years (79 out of 10,623 users [0.74%]). The adjusted hazard ratio was 1.38 (95% CI 0.98 to 1.95). There were no significant associations between use of RAS inhibitors and all-cause mortality., Conclusion: Use of ACE inhibitors was not associated with the risk of COVID-19 whereas use of ARBs was associated with a statistically non-significant increase compared to the use of CCBs. However, no significant associations were observed between prescription of either ACE inhibitors or ARBs and all-cause mortality.

Osteoporosis and ischemic heart disease (IHD) represent important public health problems. Existing research suggests an association between the two conditions beyond that attributable to shared risk factors, with a potentially causal relationship. In this study, we tested the association of bone speed of sound (SOS) from quantitative heel ultrasound with (i) measures of arterial compliance from cardiovascular magnetic resonance (aortic distensibility [AD]); (ii) finger photoplethysmography (arterial stiffness index [ASI]); and (iii) incident myocardial infarction and IHD mortality in the UK Biobank cohort. We considered the potential mediating effect of a range of blood biomarkers and cardiometabolic morbidities and evaluated differential relationships by sex, menopause status, smoking, diabetes, and obesity. Furthermore, we considered whether associations with arterial compliance explained association of SOS with ischemic cardiovascular outcomes. Higher SOS was associated with lower arterial compliance by both ASI and AD for both men and women. The relationship was most consistent with ASI, likely relating to larger sample size available for this variable (n = 159,542 versus n = 18,229). There was no clear evidence of differential relationship by menopause, smoking, diabetes, or body mass index (BMI). Blood biomarkers appeared important in mediating the association for both men and women, but with different directions of effect and did not fully explain the observed effects. In fully adjusted models, higher SOS was associated with significantly lower IHD mortality in men, but less robustly in women. The association of SOS with ASI did not explain this observation. In conclusion, our findings support a positive association between bone and vascular health with consistent patterns of association in men and women. The underlying mechanisms are complex and appear to vary by sex. © 2020 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)., (© 2020 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).)

Supported Wellbeing Centres have been set up in UK hospital trusts in an effort to mitigate the psychological impact of COVID-19 on healthcare workers, although the extent to which these are utilised and the barriers and facilitators to access are not known. The aim of the study was to determine facility usage and gather insight into employee wellbeing and the views of employees towards this provision. The study included (i) 17-week service use monitoring, (ii) employee online survey with measures of wellbeing, job stressfulness, presenteeism, turnover intentions, job satisfaction, and work engagement, as well as barriers and facilitators to accessing the Wellbeing Centres. Over 17 weeks, 14,934 facility visits were recorded across two sites (peak attendance in single week n = 2605). Facilities were highly valued, but the service model was resource intensive with 134 wellbeing buddies supporting the centres in pairs. 819 hospital employees completed an online survey (88% female; 37.7% working in COVID-19 high risk areas; 52.4% frontline workers; 55.2% had accessed a wellbeing centre). There was moderate-to-high job stress (62.9%), low wellbeing (26.1%), presenteeism (68%), and intentions to leave (31.6%). Wellbeing was higher in those that accessed a wellbeing centre. Work engagement and job satisfaction were high. Healthcare organisations are urged to mobilise access to high-quality rest spaces and psychological first aid, but this should be localised and diversified. Strategies to address presenteeism and staff retention should be prioritised, and the high dedication of healthcare workers should be recognised., Competing Interests: B.W., S.K., H.M., E.C., and J.C. are employed by the participating hospital trust but were not involved in data curation, analysis, or interpretation of findings. H.M. and E.C. were involved in service delivery. No other conflicts of interest were declared.

Background: A highly skilled workforce is required to deliver high quality evidence-based care. Clinical academic career training programmes have been developed to build capacity and capabilities of nurses, midwives and allied health professionals (NMAHPs) but it remains unclear how these skills and roles are operationalised in the healthcare context. The aim of this study was to explore the experiences of early career clinical academic NMAHPs who have undertaken, or are undertaking, clinical academic master's and doctoral studies in the United Kingdom., Methods: We conducted 17 in-depth semi-structured interviews with early career clinical academics which included; nurses, midwives and allied health professionals. The data were analysed using thematic analysis., Results: Two themes emerged from the data; identity transformation and operationalising transformation. Both these highlighted the challenges and opportunities that early clinical academic training provided to the individual and organisation in which they practiced. This required the reconceptualization of this training from the pure acquisition of skills to one of personal and professional transformation. The findings suggest that individuals, funders, and organisations may need to relinquish the notion that training is purely or largely a transactional exchange in order to establish collaborative initiatives., Conclusion: Stakeholders need to recognise that a cultural shift about the purposes of research training from a transactional to transformative approaches is required to facilitate the development of NMAHPS clinical academics, to enable them to contribute to innovative health and patient care.

Background: We examined whether the greater severity of coronavirus disease 2019 (COVID-19) amongst men and Black, Asian and Minority Ethnic (BAME) individuals is explained by cardiometabolic, socio-economic or behavioural factors., Methods: We studied 4510 UK Biobank participants tested for COVID-19 (positive, n = 1326). Multivariate logistic regression models including age, sex and ethnicity were used to test whether addition of (1) cardiometabolic factors [diabetes, hypertension, high cholesterol, prior myocardial infarction, smoking and body mass index (BMI)]; (2) 25(OH)-vitamin D; (3) poor diet; (4) Townsend deprivation score; (5) housing (home type, overcrowding) or (6) behavioural factors (sociability, risk taking) attenuated sex/ethnicity associations with COVID-19 status., Results: There was over-representation of men and BAME ethnicities in the COVID-19 positive group. BAME individuals had, on average, poorer cardiometabolic profile, lower 25(OH)-vitamin D, greater material deprivation, and were more likely to live in larger households and in flats/apartments. Male sex, BAME ethnicity, higher BMI, higher Townsend deprivation score and household overcrowding were independently associated with significantly greater odds of COVID-19. The pattern of association was consistent for men and women; cardiometabolic, socio-demographic and behavioural factors did not attenuate sex/ethnicity associations., Conclusions: In this study, sex and ethnicity differential pattern of COVID-19 was not adequately explained by variations in cardiometabolic factors, 25(OH)-vitamin D levels or socio-economic factors. Factors which underlie ethnic differences in COVID-19 may not be easily captured, and so investigation of alternative biological and genetic susceptibilities as well as more comprehensive assessment of the complex economic, social and behavioural differences should be prioritised., (© The Author(s) 2020. Published by Oxford University Press on behalf of Faculty of Public Health.)

Objective: To define the sex, age, and disease-specific associations of resting heart rate (RHR) with cardiovascular and mortality outcomes in 502,534 individuals from the UK Biobank over 7-12 years of prospective follow-up., Methods: The main outcomes were all-cause, cardiovascular, and ischaemic heart disease mortality. Additional outcomes included incident acute myocardial infarction (AMI), fatal AMI, and cancer mortality. We considered a wide range of confounders and the effects of competing hazards. Results are reported as hazard ratios (HR) for all-cause mortality and sub-distribution hazard ratios (SHR) for other outcomes with corresponding 95% confidence intervals (CI) per 10bpm increment of RHR., Results: In men, for every 10bpm increase of RHR there was 22% (HR 1.22, CI 1.20 to 1.24, p = 3×10-123) greater hazard of all-cause and 17% (SHR 1.17, CI 1.13 to 1.21, p = 5.6×10-18) greater hazard of cardiovascular mortality; for women, corresponding figures were 19% (HR 1.19, CI 1.16 to 1.22, p = 8.9×10-45) and 14% (SHR 1.14, CI 1.07 to 1.22, p = 0.00008). Associations between RHR and ischaemic outcomes were of greater magnitude amongst men than women, but with similar magnitude of association for non-cardiovascular cancer mortality [men (SHR 1.18, CI 1.15-1.21, p = 5.2×10-46); women 15% (SHR 1.15, CI 1.11-1.18, p = 3.1×10-18)]. Associations with all-cause, incident AMI, and cancer mortality were of greater magnitude at younger than older ages., Conclusions: RHR is an independent predictor of mortality, with variation by sex, age, and disease. Ischaemic disease appeared a more important driver of this relationship in men, and associations were more pronounced at younger ages., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: SEP acts as a paid consultant to Circle Cardiovascular Imaging Inc., Calgary, Canada and Servier. NCH has received consultancy, lecture fees, and honoraria from Alliance for Better Bone Health, Amgen, MSD, Eli Lilly, Servier, Shire, Radius Health, UCB, Consilient Healthcare, Kyowa Kirin and Internis Pharma. The remaining authors have nothing to disclose. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Introduction: Arterial stiffness and left ventricular (LV) hypertrophy are the key markers of hypertensive target organ damage (TOD) associated with increased cardiovascular morbidity and mortality. We have previously shown that dietary inorganic nitrate supplementation lowers blood pressure (BP) in hypertension, however, whether this approach might also improve markers of hypertensive TOD is unknown. In this study, we will investigate whether daily dietary inorganic nitrate administration reduces LV mass and improves measures of arterial stiffness., Methods and Design: NITRATE-TOD is a double-blind, randomised, single-centre, placebo-controlled phase II trial aiming to enrol 160 patients with suboptimal BP control on one or more antihypertensives. Patients will be randomised to receive 4 months once daily dose of either nitrate-rich beetroot juice or nitrate-deplete beetroot juice (placebo). The primary outcomes are reduction in LV mass and reduction in pulse wave velocity (PWV) and central BP.The study has a power of 95% for detecting a 9 g LV mass change by cardiovascular MRI (~6% change for a mildly hypertrophied heart of 150 g). For PWV, we have a power of >95% for detecting a 0.6 m/s absolute change. For central systolic BP, we have a>90% power to detect a 5.8 mm Hg difference in central systolic BP.Secondary end points include change in ultrasound flow-mediated dilation, change in plasma nitrate and nitrite concentration and change in BP., Ethics and Dissemination: The study was approved by the London-City and East Research Ethics Committee (10/H0703/98). Trial results will be published according to the Consolidated Standards of Reporting Trials statement and will be presented at conferences and reported in peer-reviewed journals., Trial Registration Number: NCT03088514., Competing Interests: Competing interests: AA is a codirector of Heartbeet Ltd, which is a start-up company that seeks to identify commercial potential of dietary nitrate., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Gastrointestinal (GI) infections cause a significant public health burden worldwide and in the UK with evidence pointing to socio-economic inequalities, particularly among children. Qualitative studies can help us understand why inequalities occur and contribute to developing more effective interventions. This study had two aims: 1. Conduct a systematic review to determine the extent and nature of UK qualitative evidence on gastrointestinal infections; 2. Use meta-ethnography to examine the influences of the differing social contexts in which people live., Methods: MEDLINE, Scopus, Web of science, CINAHL and JSTOR were searched for UK qualitative studies engaging with the risk, diagnosis, management or consequences of gastrointestinal infections from 1980 to July 2019. Five reviewers were involved in applying inclusion and exclusion criteria, extracting and synthesising data (PROSPERO CRD 42017055157)., Results: Searches identified 4080 studies, 18 met the inclusion criteria. The majority (n = 16) contained data relating to the risk of gastrointestinal infection and these made up the main synthesis. The tenets of meta-ethnography were used to glean new understandings of the role of social and environmental contexts in shaping the risk of gastrointestinal infection, specifically with respect to foodborne GI illness. Three main explanations concerning risk emerged from the data: explanations of risk in the community were underpinned by understandings of 'bugs', dirt and where food comes from; risks were negotiated in households alongside diverse processes of decision making around food; and resources available to households shaped food practices., Conclusion: This systematic review highlights the scarcity of UK qualitative evidence examining gastrointestinal infections. Apart from risk, questions around diagnosis, management and consequences of illness were largely untouched. No studies investigated patterning by socio-economic status. Nevertheless, the meta-ethnography yielded wider contextual theories and explanations as to why people might not follow food hygiene guidance, giving pointers to the types of qualitative enquiry needed to develop more effective interventions., Competing Interests: The authors have declared that no competing interests exist.

Background: Diabetes mellitus (DM) is associated with increased risk of cardiovascular disease. Detection of early cardiac changes before manifest disease develops is important. We investigated early alterations in cardiac structure and function associated with DM using cardiovascular magnetic resonance imaging., Methods: Participants from the UK Biobank Cardiovascular Magnetic Resonance Substudy, a community cohort study, without known cardiovascular disease and left ventricular ejection fraction ≥50% were included. Multivariable linear regression models were performed. The investigators were blinded to DM status., Results: A total of 3984 individuals, 45% men, (mean [SD]) age 61.3 (7.5) years, hereof 143 individuals (3.6%) with DM. There was no difference in left ventricular (LV) ejection fraction (DM versus no DM; coefficient [95% CI]: -0.86% [-1.8 to 0.5]; P =0.065), LV mass (-0.13 g/m 2 [-1.6 to 1.3], P =0.86), or right ventricular ejection fraction (-0.23% [-1.2 to 0.8], P =0.65). However, both LV and right ventricular volumes were significantly smaller in DM, (LV end-diastolic volume/m 2 : -3.46 mL/m 2 [-5.8 to -1.2], P =0.003, right ventricular end-diastolic volume/m 2 : -4.2 mL/m 2 [-6.8 to -1.7], P =0.001, LV stroke volume/m 2 : -3.0 mL/m 2 [-4.5 to -1.5], P <0.001; right ventricular stroke volume/m 2 : -3.8 mL/m 2 [-6.5 to -1.1], P =0.005), LV mass/volume: 0.026 (0.01 to 0.04) g/mL, P =0.006. Both left atrial and right atrial emptying fraction were lower in DM (right atrial emptying fraction: -6.2% [-10.2 to -2.1], P =0.003; left atrial emptying fraction:-3.5% [-6.9 to -0.1], P =0.043). LV global circumferential strain was impaired in DM (coefficient [95% CI]: 0.38% [0.01 to 0.7], P =0.045)., Conclusions: In a low-risk general population without known cardiovascular disease and with preserved LV ejection fraction, DM is associated with early changes in all 4 cardiac chambers. These findings suggest that diabetic cardiomyopathy is not a regional condition of the LV but affects the heart globally.

Background: Persistent postsurgical pain is common and affects quality of life. The hypothesis was that use of pregabalin and ketamine would prevent persistent pain after cardiac surgery., Methods: This randomized, double-blind, placebo-controlled trial was undertaken at two cardiac surgery centers in the United Kingdom. Adults without chronic pain and undergoing any elective cardiac surgery patients via sternotomy were randomly assigned to receive either usual care, pregabalin (150 mg preoperatively and twice daily for 14 postoperative days) alone, or pregabalin in combination with a 48-h postoperative infusion of intravenous ketamine at 0.1 mg · kg · h. The primary endpoints were prevalence of clinically significant pain at 3 and 6 months after surgery, defined as a pain score on the numeric rating scale of 4 or higher (out of 10) after a functional assessment of three maximal coughs. The secondary outcomes included acute pain, opioid use, and safety measures, as well as long-term neuropathic pain, analgesic requirement, and quality of life., Results: In total, 150 patients were randomized, with 17 withdrawals from treatment and 2 losses to follow-up but with data analyzed for all participants on an intention-to-treat basis. The prevalence of pain was lower at 3 postoperative months for pregabalin alone (6% [3 of 50]) and in combination with ketamine (2% [1 of 50]) compared to the control group (34% [17 of 50]; odds ratio = 0.126 [0.022 to 0.5], P = 0.0008; and 0.041 [0.0009 to 0.28], P < 0.0001, respectively) and at 6 months for pregabalin alone (6% [3 of 50]) and in combination with ketamine 0% (0 of 5) compared to the control group (28% [14 of 50]; odds ratio = 0.167 [0.029 to 0.7], P = 0.006; and 0.000 [0 to 0.24], P < 0.0001). Diplopia was more common in both active arms., Conclusions: Preoperative administration of 150 mg of pregabalin and postoperative continuation twice daily for 14 days significantly lowered the prevalence of persistent pain after cardiac surgery.

Understanding the epidemiological dynamics of highly pathogenic avian influenza virus (HPAIV) in wild birds is crucial for guiding effective surveillance and control measures. The spread of H5 HPAIV has been well characterized over large geographical and temporal scales. However, information about the detailed dynamics and demographics of individual outbreaks in wild birds is rare and important epidemiological parameters remain unknown. We present data from a wild population of long-lived birds (mute swans; Cygnus olor) that has experienced three outbreaks of related H5 HPAIVs in the past decade, specifically, H5N1 (2007), H5N8 (2016) and H5N6 (2017). Detailed demographic data were available and intense sampling was conducted before and after the outbreaks; hence the population is unusually suitable for exploring the natural epidemiology, evolution and ecology of HPAIV in wild birds. We show that key epidemiological features remain remarkably consistent across multiple outbreaks, including the timing of virus incursion and outbreak duration, and the presence of a strong age-structure in morbidity that likely arises from an equivalent age-structure in immunological responses. The predictability of these features across a series of outbreaks in a complex natural population is striking and contributes to our understanding of HPAIV in wild birds. This article is part of the theme issue 'Modelling infectious disease outbreaks in humans, animals and plants: approaches and important themes'. This issue is linked with the subsequent theme issue 'Modelling infectious disease outbreaks in humans, animals and plants: epidemic forecasting and control'.

Controlled organ donation after circulatory death (DCD) has recently been revived in the UK, as part of attempts to increase organ donation rates. The re-introduction of DCD has subsequently become the focus of bioethical controversy, since it necessitates intervening in the care of dying patients to obtain quality donor organs. Transplant policy responses to these concerns have generated new legal and ethical guidelines to address uncertainties around DCD, producing claims that the UK has overcome' the ethical challenge of DCD. In contrast, by drawing on Lynch's call to 'respecify' ethics, this paper argues that ethics in DCD cannot be reduced to abstract directives for practice, but, instead, are composed and dealt with as an organisational problem. To do this, I utilise data from an ethnographic study examining the production of the 'minority ethnic organ donor' within UK organ donation settings; in particular, the data pertains to a case hospital which was in the process of developing a DCD programme during the period of fieldwork. Findings show that the ethics of DCD are encountered as practical sets of problems, constructed in relation to particular institutional locales. I describe how these issues are worked-around by creating conditions to make DCD organisationally possible, and through the animation of standard procedures into acceptable forms of practice. I argue that ethics in DCD go far beyond normative bioethical principles, to encompass concerns around: the reputation of hospital Trusts, public perceptions of organ donation, the welfare of potential donor families, and challenges to the work of health professionals caring for dying patients. The paper enriches understanding of ethics in science and medicine by showing how ethics are assembled and negotiated as a practical-organisational concern, and calls for further examination of how DCD gets constructed as a potential problem and is made to happen in practice., (Crown Copyright © 2018. Published by Elsevier Ltd. All rights reserved.)

Background and Aims: Patients with familial hypercholesterolaemia (FH) have an elevated risk of coronary heart disease (CHD). Here we compare changes in CHD mortality in patients with heterozygous (FH) pre 1992, before lipid-lowering therapy with statins was used routinely, and in the periods 1992-2008 and 2008-2016., Methods: 1903 Definite (DFH) and 1650 Possible (PFH) patients (51% women) aged 20-79 years, recruited from 21 lipid clinics in the United Kingdom and followed prospectively between 1980 and 2016 for 67,060 person-years. The CHD standardised mortality ratio (SMR) compared to the population in England and Wales was calculated (with 95% Confidence intervals)., Results: There were 585 deaths, including 252 from CHD. Overall, the observed 2.4-fold excess coronary mortality for treated DFH post-1991 was significantly higher than the 1.78 excess for PFH (35% 95% CI 3%-76%). In patients with DFH and established coronary disease, there was a significant excess coronary mortality in all time periods, but in men it was reduced from a 4.83-fold excess (2.32-8.89) pre-1992 to 4.66 (3.46-6.14) in 1992-2008 and 2.51 (1.01-5.17) post-2008, while in women the corresponding values were 7.23 (2.65-15.73), 4.42 (2.70-6.82) and 6.34 (2.06-14.81). Primary prevention in men with DFH resulted in a progressive reduction in coronary mortality over the three time-periods, with no excess mortality evident post-2008 (0.89 (0.29-2.08)), although in women the excess persisted (post-2008 3.65 (1.75-6.72))., Conclusions: The results confirm the benefit of statin treatment in reducing CHD mortality, but suggest that FH patients with pre-existing CHD and women with FH may not be treated adequately., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: For children with familial hypercholesterolemia (FH), UK guidelines recommend consideration of statin therapy by age 10 years and dietary and lifestyle advice to maintain an ideal body weight., Objectives: The objective of the study is to use the UK Paediatric Familial Hypercholesterolemia Register to determine: (1) the prevalence of plasma markers of liver toxicity and muscle damage in statin-treated FH children; (2) the prevalence of obesity in FH children compared to the UK general population; and (3) to compare growth rates in statin-treated and nontreated children., Methods: Differences in registration and 1-year characteristics were compared by Mann-Whitney U tests. Age and gender body mass index percentiles were compared to UK children's growth charts., Results: In 300 children (51% boys, 75% Caucasian, untreated mean [standard deviation] low-density lipoprotein cholesterol 5.50 [1.49] mmol/L), the proportion on statins varied significantly (P < .005) by age group (<5 years = 0%, 5-10 years = 16.7%, 10-15 years = 57.1%, and >15 years = 73.2%). Statin treatment reduced low-density lipoprotein cholesterol by 31% (1.84 [1.43] mmol/L), and no child showed elevated levels of markers of liver toxicity or muscle damage. At registration, 16.9% of the FH children were overweight (>85th percentile) and 11.1% were obese (>95th percentile) vs reported in 21.2% in UK non-FH children. There was no difference in annual growth rate in statin vs no-statin groups (age-adjusted weight increases 3.58 vs 3.53 kg; P = .91, height 4.45 vs 4.60 cm P = .73)., Conclusions: We show no evidence for statin-related safety or growth issues, but many FH children over the age of 10 years are not on statin treatment. Fewer UK children with FH are obese compared to UK non-FH children., (Copyright © 2017 National Lipid Association. Published by Elsevier Inc. All rights reserved.)