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Background Acute kidney injury (AKI) is common after liver transplantation (LT). Induction with interleukin-2 receptor antagonists is often used as a “renal-sparing” strategy. The aim of this study was to assess this approach in a real-world setting in an LT center. Methods A retrospective cohort analysis of LTs between 2011 and 2018 was performed to assess the impact of a renal-sparing strategy using basiliximab in conjunction with mycophenolate mofetil and corticosteroids from day 0 post-LT along with delayed introduction of tacrolimus. This was compared with a group receiving tacrolimus, mycophenolate mofetil, and corticosteroids from the outset. Results The renal-sparing regimen was associated with significantly lower incidence of all-stage AKI at day 7 post-LT (36% vs 55%, P = .006) and less decline in renal function at 3 months (39% vs 57%, P = .01). No further significant differences in renal outcomes were observed at other time points on follow-up to 1 year post-LT. There was no significant difference in the incidence of acute cellular rejection, inpatient length of stay or graft survival. The decision to adopt a renal-sparing regimen was predominantly made on a clinically reactive basis within the first 24 hours post-LT in 77%, and was preordained in 23%. Cost-effectiveness analysis did not find evidence of a significant cost saving when using a renal-sparing strategy. Conclusion This study provides real-world analysis of the use of a renal-sparing immunosuppression regimen in LT. Although improvements in incidence of AKI in the short term were demonstrated, this did not translate to cost savings or improved renal outcomes after 3 months.

Background Patients with chronic kidney disease (CKD) are more prone to severe infection. Vaccination is a key strategy to reduce this risk. Some studies suggest vaccine efficacy may be reduced in patients with CKD, despite preserved maintenance of long-term responses to some pathogens and vaccines. Here, we investigated immune responses to 2 vaccines in patients with CKD to identify predictors of immunological responsiveness. Methods Individuals >65 years old, with or without nondialysis CKD (n = 36 and 29, respectively), were vaccinated with a nonadjuvanted seasonal influenza vaccine (T-dependent) and Pneumovax23 (23-valent pneumococcal polysaccharide [PPV23], T-independent). Humoral responses were measured at baseline, day 28, and 6 months. Lymphocyte subset and plasma cell/blast analyses were performed using flow cytometry. Cytomegalovirus (CMV) serotyping was assessed by enzyme-linked immunosorbent assay. Results Only modest responsiveness was observed to both vaccines, independent of CKD status (25% adequate response in controls vs. 12%–18% in the CKD group). Unexpectedly, previous immunization with PPV23 (median 10-year interval) and CMV seropositivity were associated with poor PPV23 responsiveness in both study groups (P < .001 and .003, respectively; multivariable linear regression model). Patients with CKD displayed expanded circulating populations of T helper 2 and regulatory T cells, which were unrelated to vaccine responses. Despite fewer circulating B cells, patients with CKD were able to mount a similar day 7 plasma cell/blast response to controls. Conclusion Patients with nondialysis CKD can respond similarly to vaccines as age- and sex-matched healthy individuals. CKD patients display an immune signature that is independent of vaccine responsiveness. Prior PPV23 immunization and CMV infection may influence responsiveness to vaccination. Clinical Trials Registration. NCT02535052, Patients with nondialysis Chronic Kidney Disease (CKD) can mount similar responses to vaccination as controls. Subtle changes in lymphocyte phenotype are seen in CKD when controlled for effect of Cytomegalovirus (CMV). Latent CMV infection and previous PPV23 vaccination are associated with poorer vaccine responses.

Neutrophil dysfunction has been described with age, appears exaggerated in infection, with altered phosphoinositol signaling a potential mechanism. However, functional aging is heterogeneous. Frailty is a negative health status and is more common in older adults. We hypothesized that neutrophil migration may be compromised in frailty, associated with the degree of frailty experienced by the older person. We compared measures of frailty, neutrophil function, and systemic inflammation in 40 young and 77 older community-dwelling adults in the United Kingdom. Systemic neutrophils exhibited an age-associated reduction in the accuracy of migration (chemotaxis) which was further blunted with frailty. The degree of migratory inaccuracy correlated with physical (adjusted hand grip strength) and cognitive (Stroop test) markers of frailty. Regression analysis demonstrated that age, Charlson comorbidity index, and frailty index were able to predict neutrophil chemotaxis. Reduced chemotaxis of neutrophils from frail adults could be reversed using selective PI3K inhibitors. Exposure of neutrophils from young adults to plasma from chronically inflamed frail older adults could not recapitulate the migratory deficit in vitro, and there were no relationships with systemic inflammation and neutrophil dysfunction. Frailty exaggerated the neutrophil deficits seen with advanced age but aspects of the frailty-associated deficit in neutrophil function are rescuable and thus potentially form a therapeutic target to improve outcomes from infection in older adults.

Systemic autoimmune inflammatory disorders confer a higher risk of cardiovascular (CV) disease leading to increased morbidity and mortality and reduced life expectancy compared to the general population. CV risk in systemic sclerosis (SSc) has not been studied extensively but surrogate markers of atherosclerosis namely carotid intima media thickness (cIMT) and pulse wave velocity (PWV) are impaired in some but not all studies in SSc patients. The aim of this study was to investigate the prevalence of subclinical atherosclerosis assessed by cIMT and PWV between two well-characterized SSc and Rheumatoid Arthritis (RA) cohorts. Consecutive SSc patients attending the Scleroderma Clinic were compared with RA patients recruited in the Dudley Rheumatoid Arthritis Co-morbidity Cohort (DRACCO), a prospective study examining CV burden in RA. Augmentation Index (Aix75) and cIMT were measured in all participants. Propensity score matching was utilised to select patients from the two cohorts with similar demographic characteristics, CV risk factors and inflammatory load. Unpaired analysis was performed using unpaired t test for continuous variables and χ2 test for dichotomous variables. Statistical analysis was repeated using paired t test for continuous normal variables and McNemar’s test for dichotomous variables. Fifty five age- and sex-matched SSc and RA patients were included in the analysis. No difference was demonstrated between SSc and RA subjects regarding cIMT (0.66 mm vs 0.63 mm, respectively) and Aix75% measurements (33.4 vs 31.7, respectively) neither in paired (p = 0.623 for cIMT and p = 0.204 for Aix%) nor in unpaired t test analysis (p = 0.137 for cIMT and p = 0.397 for AIx%). The results of this comparative study show that subclinical atherosclerosis is comparable between SSc and RA, a systemic disease with well-defined high atherosclerotic burden. Such findings underscore the importance of CV risk management in SSc in parallel with other disease-related manifestations.

BACKGROUND: Infections remain a part of the natural course of cancer, and lung cancer patients often present with some form of respiratory infection that can lead to their ultimate demise. METHODS: Data was gathered concerning all unplanned hospital admissions (UHAs) to our centre from three separate patient cohorts; non-small cell lung cancer (NSCLC) patients (cohort 1), “other cancer” patients (breast, prostate, colon) (cohort 2) and all non-cancer patients (cohort 3). RESULTS: Across the three cohorts, there were 455, 1,190 and 54,158 individual patient UHAs to our centre respectively. Within the NSCLC cohort, 164 UHAs were as a direct result of pneumonia (36.0%), compared to 1.3% and 2.2% in the other two cohorts (P

Objective:Vitamin A (VA) deficiency, more common in low- and middle-income countries (LMIC) secondary to malnutrition, is associated with increased morbidity and mortality. The prevalence and impact of VA deficiency in high-income countries (HIC) where chronic conditions may predispose is less well understood.Design:Interpretation of serum retinol may be affected by inflammation, so C-reactive protein (CRP) levels were sought. Binary logistic regression and generalised estimating equations were performed to review the relationship between CRP and VA.Setting:We examined the scale of low and deficient VA status in our tertiary University Teaching Hospital (HIC).Participants:Patients undergoing serum retinol concentrations 2012–2016 were identified from laboratory records, and records examined.Results:Totally, 628 assays were requested, with eighty-two patients VA low (0·7–0·99 Umol/l) or deficient (Conclusion:The majority of patients tested either were replete or likely to have abnormal VA levels due to concomitant inflammation. A minority of patients had signs and symptoms of VA deficiency and was a cause of significant morbidity, but aetiology differs from LMIC, overwhelmingly malabsorption, most commonly secondary to surgery or hepatobiliary disease. A correlation between inflammation and low VA levels exists, which raises the possibility that requesting a VA level in an asymptomatic patient with active inflammation may be of questionable benefit.

Data were collected on patients admitted to the Queen Elizabeth Hospital Birmingham with type-1 myocardial infarction during 2016 and 2017 inclusively, who were treated by percutaneous intervention and had pre-discharge transthoracic echocardiography. The data were obtained from prospectively maintained hospital databases and records. Echocardiography was performed and reported contemporaneously by accredited echocardiographers. The purpose was to understand the prevalence and characteristics of mitral regurgitation (MR) after acute MI, including patients with ST-elevation (STEMI) and non-ST elevation MI (NSTEMI). MR was observed in 294/1000 patients with the following relative severities: mild = 76%, moderate = 21%, severe = 3% [1]. MR was graded by multiparametric quantification including proximal isolvelocity surface area (PISA), vena contracta (VC), effective regurgitant orifice area (EROA) and regurgitant volume (RVol). Amongst all patients with MR (n=294), PISA was performed in 89/294 (30%), VC 75/294 (26%), EROA in 53/294 (18%) and RVol in 26/294 (9%). Amongst patients with moderate or severe MR (n=70), PISA was performed in 57/70 (81%), VC in 55/70 (79%), EROA in 46/70 (66%) and RVol in 25/70 (36%). Characteristics of MR following acute MI were also assessed including frequency of reported leaflet thickness (259/294 = 88%) and mitral annular calcification (102/294 = 35%). Furthermore, the effect of MI on pre-existing MR was investigated and patients with pre-existing MR who continue to have MR after acute MI were found to have progression of MR by one grade in approximately 25% of cases. Finally, using Cox proportional hazards univariate analysis, significant factors associated with mortality in patients with MR post-MI include age (HR 1.065; 95% CI 1.035-1.096; p

Chronic gastroesophageal reflux predisposes to the development of esophageal adenocarcinoma (EAC). Asthma and medication to treat it are associated with gastroesophageal reflux and EAC. We studied subjects with chronic obstructive pulmonary disease (COPD) to examine the relationship between COPD and medication used to treat it, and the risk of reflux esophagitis, Barrett's esophagus, and EAC.A case-control study from the UK General Practice Research Database was conducted. Cases were aged 50 or above with a diagnosis of COPD and were matched with controls without a diagnosis of COPD by age, general practitioners practice, and time on the database. EAC was confirmed by cross-referencing cancer registry data. Cox-regression analysis was performed to assess the relationship between COPD, reflux esophagitis, Barrett's esophagus, and EAC.A total of 45,141 cases were studied [24,464 male, age 75 (50 to 100) years]. Among COPD cases there were 55 esophageal cancers (30 EAC) and 506 Barrett's esophagus, compared with 62 (34 EAC) and 329 Barrett's esophagus among controls. COPD was not associated with EAC on univariable [0.92 (0.56 to 1.50), P=0.73] and multivariable analysis [0.85 (0.52 to 1.40), P=0.53]. COPD was however, associated with Barrett's esophagus on univariable [0.92 (0.56 to 1.50), P=0.73] and multivariable [1.53 (1.31 to 1.78), P0.001] analysis and reflux esophagitis on univariable [1.41 (1.36 to 1.48), P0.001] and multivariable [1.33 (1.27 to 1.40), P0.001] analysis.COPD is associated with an increased risk of reflux esophagitis and Barrett's esophagus but not EAC.

Rationale: Population studies suggest improved sepsis outcomes with statins, but the results of randomized controlled trials in patients with sepsis and organ dysfunction in critical care settings have broadly been negative. In vitro data suggest that statins modulate age-related neutrophil functions, improving neutrophil responses to infection, but only in older patients and at high doses. Objectives: To determine if high-dose simvastatin improves neutrophil functions and is safe and tolerated in hospitalized older adults with community-acquired pneumonia with sepsis (CAP + S) not admitted to critical care. Methods: We conducted a randomized, double-blind, placebo-controlled pilot study of simvastatin 80 mg or placebo for 7 days for patients with CAP + S aged 55 years or older admitted to a secondary care hospital. The Day 4 primary endpoint was change in neutrophil extracellular trap formation (NETosis). Day 4 secondary endpoints included neutrophil chemotaxis, safety and tolerability, Sequential Organ Failure Assessment score, mortality, readmission, and markers of tissue degradation/inflammation. Measurements and Main Results: Four days of simvastatin adjuvant therapy in patients with CAP + S was associated with improvements in systemic neutrophil function (NETosis and chemotaxis), a reduction in systemic neutrophil elastase burden, and improved Sequential Organ Failure Assessment scores compared with placebo. A post hoc analysis demonstrated that simvastatin therapy was associated with improved hospitalization-free survival compared with placebo. Simvastatin was well tolerated in this elderly and multimorbid patient group with common coprescription of macrolide antibiotics. Conclusions: This pilot study supports high-dose simvastatin as an adjuvant therapy for CAP + S in an older and milder disease cohort than assessed previously. A definitive multicenter study is now warranted in this population to assess the likelihood of benefit and harm. Clinical trial registered with EudraCT (2012-00343-29).

We thank M.M. Speeckaert and co-workers for their interest in our paper about vitamin D status and seroconversion for coronavirus disease 2019 (COVID-19) in UK healthcare workers [1]. We agree with the authors that vitamin D binding protein (DBP) is important in determining serum 25(OH)D3 levels. The majority of vitamin D in the circulation is bound to DBP, also known as gc-globulin, which has actin-binding and immunomodulatory functions independent of vitamin D carriage [2]. DBP levels may be particularly relevant to determining 25(OH)D3 levels in severely ill COVID-19 patients with acute respiratory distress syndrome (ARDS), as we have previously demonstrated that DBP is a negative acute phase protein with levels dropping by about a third in patients with ARDS [3]. This tends to lower circulating total vitamin D but releases free 25(OH)D that can be taken up by cells of the immune system and epithelial cells. The consequences of changes in serum 25(OH)D during illness are, therefore, complex and difficult to interpret [4]. Genome-wide association analyses have shown that single nucleotide polymorphisms (SNPs) in the gene for DBP (GC) are important contributors to the genetic component of circulating 25D concentrations, but this is still a relatively small proportion of overall serum 25D levels, and it is unclear how these SNPs impact DBP/25D homeostasis in the setting of disease., This work outlines the potential importance of vitamin D binding protein and vitamin D in immune function and COVID-19 infection https://bit.ly/3byTaO5

Mitral regurgitation (MR) following acute myocardial infarction (AMI) worsens prognosis and reports of prevalence vary significantly. The objective was to determine prevalence, risk factors, and outcomes related to MR following AMI. We identified 1000 consecutive patients admitted with AMI in 2016/17 treated by percutaneous coronary intervention with pre-discharge transthoracic echocardiography. MR was observed in 294 of 1000 (29%), graded as mild (n = 224 [76%]), moderate (n = 61 [21%]) and severe (n = 9 [3%]). Compared with patients without MR, patients with MR were older (70 ± 12 vs 63 ± 13 years; p0.001), with worse left ventricular ejection fraction (LVEF) (52 ± 15% vs 55 ± 11%; p0.001) and creatinine clearance (69 ± 33 ml/min vs 90 ± 39 ml/min; p0.001). They also had higher rates of hypertension (64% vs 55%; p = 0.012), heart failure (3.4% vs 1.1%; p = 0.014), previous MI (28% vs 20%; p = 0.005) and severe flow-limitation in the circumflex (50% vs 33%; p0.001) or right coronary artery (51% vs 42%; p = 0.014). Prevalence and severity of MR were unaffected by AMI subtype. Revascularization later than 72 hours from symptom-onset was associated with increased likelihood of MR (33% vs 25%; p = 0.036) in patients with non-ST elevation myocardial infarction (NSTEMI). After a mean of 3.2 years, 56 of 288 (19%) patients with untreated MR died. Age and LVEF independently predicted mortality. The presence of even mild MR was associated with increased mortality (p = 0.029), despite accounting for confounders. In conclusion, MR is observed in over one-quarter of patients after AMI and associated with lower survival, even when mild. Prevalence and severity are independent of MI subtype, but MR was more common with delayed revascularization following NSTEMI.

BackgroundPirfenidone and nintedanib are the only disease-modifying treatments available for idiopathic pulmonary fibrosis (IPF). Our aim was to test their effectiveness and safety in clinical practice.MethodsThis is a single-centre retrospective observational study undertaken at a specialised interstitial lung disease centre in England. Data including progression-free survival (PFS), mortality and drug tolerability were compared between patients with IPF on antifibrotic therapies and an untreated control group who had a forced vital capacity percentage (FVC %) predicted within the licensed antifibrotic treatment range.Results104 patients received antifibrotic therapies and 64 control patients were identified. PFS at 6 months was significantly greater in the antifibrotic group (75.0%) compared with the control group (56.3%) (p=0.012). PFS was not significant at 12 or 18 months when comparing the antifibrotic group with the control group. The 12-month post-treatment mean decline in FVC % predicted (−4.6±6.2%) was significantly less than the 12-month pretreatment decline (−10.4±11.8%) (p=0.039). The 12-month mortality rate was not significantly different between the antifibrotic group (25.3%) and the control group (35.5%) (p=0.132). Baseline Body Mass Index of≤25, baseline diffusion capacity for carbon monoxide percentage predicted of ≤35 and antifibrotic discontinuation within 3 months were independent predictors of 12-month mortality. Antifibrotic discontinuation was significantly higher by 3 and 6 months for patients on pirfenidone than those on nintedanib (p=0.006 and p=0.044, respectively). Discontinuation at 12 months was not significantly different (p=0.381).ConclusionsThis real-world study revealed that antifibrotics are having promising effects on PFS, lung function and mortality. These findings may favour commencement of nintedanib as first-line antifibrotic therapy, given the lower rates of early treatment discontinuation, although further studies are required to investigate this.

Objectives Relapses affect 30–50% of patients with ANCA-associated vasculitis (AAV) over 5 years, necessitating long-term treatment. Although there have been studies looking at predictors of relapse in AAV, this research has yet to translate clinically into guidance on tailored therapy. The aim of this systematic review was to identify and meta-analyse existing risk factors from the literature and produce a model to calculate individualised patient risk of relapse. Method A search strategy was developed to include all studies identifying predictors of AAV relapse using multivariate analysis. Individual risk factors were extracted and pooled hazard ratios (HRs) calculated. A model to predict the time to first relapse based on identified risk factors was tested retrospectively using a cohort of patients with AAV. Results The review of 2674 abstracts identified 117 papers for full text review, with 16 eligible for inclusion. Pooled HRs were calculated from significant risk factors, including anti-PR3 ANCA positivity [HR 1.69 (95% CI 1.46, 1.94)], cardiovascular involvement [HR 1.78 (95% CI 1.26, 2.53)], creatinine >200 µmol/l (relative to creatinine ≤100) [HR 0.39 (95% CI 0.22, 0.69)] and creatinine 101–200 µmol/l [HR 0.81 (95% CI 0.77, 0.85)]. Using data from 182 AAV patients to validate the model gave a C-statistic of 0.61. Conclusion Anti-PR3 ANCA positivity, lower serum creatinine and cardiovascular system involvement are all associated with an increased risk of relapse, and a combination of these risk factors can be used to predict the individualised risk of relapse. In order to produce a clinically useful model to stratify risk, we need to identify more risk factors, with a focus on robust biomarkers.

SummaryBackgroundIt is clear that in UK healthcare workers, COVID-19 infections and deaths were more likely to be in staff who were of BAME origin. This has led to much speculation about the role of vitamin D in healthcare worker COVID-19 infections. We aimed to determine the prevalence of vitamin D deficiency in NHS staff who have isolated with symptoms suggestive of COVID-19 and relate this to vitamin D status.MethodsWe recruited NHS healthcare workers between 12thto 22ndMay 2020 as part of the COVID-19 convalescent immunity study (COCO). We measured anti-SARS-Cov-2 antibodies using a combined IgG, IgA and IgM ELISA (The Binding Site). Vitamin D status was determined by measurement of serum 25(OH)D3using the AB SCIEX Triple Quad 4500 mass spectrometry system.FindingsOf the 392 NHS healthcare workers, 214 (55%) had seroconverted for COVID-19. A total of 61 (15.6%) members of staff were vitamin D deficient (30 kg/m2), and were male. Multivariate analysis revealed that BAME and COVID-19 seroconversion were independent predictors of vitamin D deficiency. Staff who were vitamin D deficient were more likely to self-report symptoms of body aches and pains but importantly not the respiratory symptoms of cough and breathlessness. Vitamin D levels were lower in those COVID-19 positive staff who reported fever, but this did not reach statistical significance. Within the whole cohort there was an increase in seroconversion in staff with vitamin D deficiency compared to those without vitamin D deficiency (n=44/61, 72%vsn=170/331, 51%; p=0·003); this was particularly marked in the proportion of BAME males who were vitamin D deficient compared to non-vitamin D deficient BAME males (n=17/18, 94%vsn=12/23, 52%; p=0·005). Multivariate analysis revealed that vitamin D deficiency was an independent risk factor for seroconversion (OR 2·6, 95%CI 1·41–4·80; p=0·002).InterpretationIn those healthcare workers who have isolated due to symptoms of COVID-19, those of BAME ethnicity are at the highest risk of vitamin D deficiency. Vitamin D deficiency is a risk factor for COVID-19 seroconversion for NHS healthcare workers especially in BAME male staff.FundingThis study was funded internally by the University of Birmingham and University Hospitals Birmingham NHS Foundation Trust and supported by the National Institute for Health Research (NIHR)/Wellcome Trust Birmingham Clinical Research Facility. AAF and DRT are funded by the Medical Research Council (MR/S002782/1). The Binding Site (Edgbaston, UK) have provided reagents and plates for the SARS-CoV-2 ELISA free of charge.Research in contextEvidence before this studyThe ongoing COVID-19 pandemic has raised several questions, one of which is whether individuals with vitamin D deficiency were at a greater risk of being infected or having a severe outcome if infected. Among UK healthcare workers, and indeed the general population, individuals of BAME ethnicity are disproportionately affected by COVID-19. It is well established that individuals of BAME ethnicity have a higher prevalence of vitamin D deficiency, but it is unknown if vitamin D deficiency among UK NHS workers was connected to the risk of COVID-19 infection. Our search of the literature revealed no previous studies have established the prevalence of vitamin D deficiency within a UK NHS trust. Unsurprisingly, there is also no evidence to suggest if vitamin D deficiency was connected to the risk of infection among UK healthcare workers.Added value of this studyIn this study of healthcare workers who had isolated for COVID-19 symptoms towards the end of UK surge within a large UK NHS trust, 15.6% were vitamin D deficient. Our data also reveal that healthcare workers of BAME ethnicity and those who had seroconverted for COVID-19 were more likely to be vitamin D deficient. Multivariate analysis also show that vitamin D deficiency was the only predictor of COVID-19 seroconversion. Vitamin D deficient healthcare workers that are BAME and male had a 94% seroconversion for COVID-19 compared to non-deficient BAME males suggesting they are more at risk of COVID-19 if vitamin D deficient.Implications of all the available evidenceThere is an increased risk of COVID-19 infection in healthcare workers with vitamin D deficiency. Our data adds to the emerging evidence from studies in the UK and across the globe that individuals with severe COVID-19 are more vitamin D deficient than those with mild disease. Finally, ours and the available evidence demonstrate vitamin D supplementation in individuals at risk of vitamin D deficiency or shown to be deficient may help alleviate the impact of COVID-19.

Background South Asians have a higher risk of cardiovascular disease (CVD). Rheumatoid arthritis (RA) increases the risk of premature atherosclerosis. We investigated whether there was a substantial difference in the level of CVD risk knowledge among patients of South Asian origin with RA in India and in the UK. Methods In this cross-sectional survey, patients of South Asian origin with RA from India and the UK were recruited from secondary care settings. Data were collected via Heart Disease Fact Questionnaire-Rheumatoid Arthritis (HDFQ-RA), a validated self-completion questionnaire. The HDFQ-RA was translated into Hindi and piloted among patients from South Asian background before use. Additionally, clinical and demographic data was collected. Results Among 118 patients from each country, 84% were female and they had similar age, education level, employment status and co-morbidities. Patients from India had longer disease duration (5.5 years versus 4.1 years (p = 0.012) whereas those from the UK had higher disease activity score (4.0 + 0.8 versus 3.1 + 0.7, p Conclusion Patients of South Asians origin with RA from both countries had limited knowledge about CVD risk. There is a need to educate them about CVD risk during consultation, as this will result in better outcomes.

Community acquired pneumonia is the leading cause of death from infection. Early identification of severe pneumonia allows early intervention and improves outcomes for patients. We have demonstrated that pneumonia-specific tools were superior to other risk stratification methods in predicting 30-day mortality; however, CURB65 has limited ability to predict 30-day mortality in our study(1). We sought to develop a risk stratification tool which was a better predictor of mortality. Using a dataset previously described (1) we used a combination of univariate and multivariate analysis to identify factors significantly associated with 30-day mortality; age, respiratory rate, oxygen requirement,temperature,urea,albumin, neutrophil:lymphocyte ratio, blood pH and lactate. The first set of data on admission was used. 1271 cases were available for scoring. ROC analysis demonstrated an AUC of 0.811 for BCAPS, CURB65 generated an AUC of 0.69. In summary we have generated a simple bedside tool which is able to accurately predict 30-day mortality in CAP at the point of admission to hospital. This tool requires further validation in external sites and larger databases to ensure generalisability. (1): PMID:31258921

Background Aspirin forms a cornerstone of management in patients with established cardiovascular disease (CVD). Despite proven efficacy, variability of aspirin response has long been recognised, with early studies suggesting rates of high on treatment platelet reactivity (HTPR) as ranging between 5 and 45%. Whether aspirin responsiveness relates to long-term prognosis in patients with CVD is unknown. Methods A prospective, single-centre analysis of 224 troponin positive non-ST elevation myocardial infarction (NSTEMI) patients undergoing coronary angiography. Aspirin-naive patients were loaded with 300 mg aspirin and maintained on 75 mg daily. Blood samples were obtained at the time of angiography and the VerifyNow Aspirin assay utilised to determine aspirin effect. The primary end point was all-cause mortality at 10 years. Results Time from aspirin loading (or admission on aspirin) to angiography was 4.9 ± 2.7 days. Platelet aggregation results, expressed as aspirin reaction units (ARU) were divided into tertiles: T1 (ARU 363–405) (n = 76), T2 (ARU 406–436) (n = 76), T3 (ARU 437–596) (n = 72). Higher ARU values were associated with increased mortality (log rank, p = 0.009), with those in the T3 having a 3-fold higher rate of events than those in the T1 (HR 3.03 [95% CI 1.33–6.99], p = 0.009) over a 10-year follow up. Conclusion Our study demonstrates that aspirin responsiveness is directly related to 10-year survival and may identify patients who may benefit from additional antithrombotic therapy. Further, ARU values less than the previously defined cut off 550 are associated with reduced survival at 10 years.

Background South Asians have a higher risk of cardiovascular disease (CVD). Rheumatoid arthritis (RA) increases the risk of premature atherosclerosis. Therefore, we compared the level of CVD risk knowledge among patients of South Asian origin with RA in India and in the UK. Methods In this cross-sectional survey, patients of South Asian origin with RA from India and the UK were recruited from secondary care settings. Data were collected via Heart Disease Fact Questionnaire-Rheumatoid Arthritis (HDFQ-RA), a validated self-completion questionnaire. The HDFQ-RA was translated into Hindi and piloted among patients from South Asian background before use. Additionally, clinical and demographic data was collected. Results Among 118 patients from each country, 84% were female and they had similar age, education level, employment status and co-morbidities. Patients from India had longer disease duration (5.5 years versus 4.1 years (p = 0.012) whereas those from the UK had higher disease activity score (4.0 + 0.8 versus 3.1 + 0.7, p < 0.01). Regarding modifiable risk factors for CVD only 44.6% from India and 45.4% in the UK were aware of them (p=ns). However, awareness of the link between RA and increased risk of CVD was even more limited (38.1% in India and 40.7% in UK (p=ns). Conclusion Patients of South Asians origin with RA from both countries had limited knowledge about CVD risk. There is a need to educate them about CVD risk during consultation, as this will result in better outcomes. Disclosures K. Kumar None. S. Arya None. P. Nightingale None. T. Sheeran None. A. Aggarwal None.

IntroductionSarcopenia is a progressive loss in muscle mass, strength and function, the adverse consequences of which are severe, affecting quality of life and placing an increasing burden on social and healthcare systems. Vitamin D status is known to be associated with markers of sarcopenia, namely muscle mass, strength and function. Also, resistance exercise training (RET) is currently the only proven intervention to treat sarcopenia. However, very little data exist on the influence of combining the two interventions of vitamin D supplementation and resistance exercise training, although a recent systematic review provides tentative support for the current study’s hypothesis that the combined intervention may further improve musculoskeletal function above exercise training alone. The aim of the present study is to determine whether vitamin D3supplementation is any more effective in improving musculoskeletal function when combined with RET compared with exercise training alone in older adults.Methods and analysisThis double-blinded randomised placebo-controlled trial will recruit a target of 127 eligible men and women aged ≥65 years living independently or in sheltered housing within the Birmingham area to two groups: (1) 6 months RET and placebo or (2) 6 months RET and 800 IU/d vitamin D3. Measures of muscle power (Nottingham Power Rig), body composition (dual energy X-ray absorptiometry), muscle function (short physical performance battery, timed up and go), falls and fractures as events will be assessed. Assessments will take place at baseline and postintervention, with intermittent monitoring of bone turnover, calcium and vitamin D. The primary outcome will be lower limb extensor power output. Analyses of within-group changes and between-group differences in outcome measures are planned.Ethics and disseminationThe EXVITD study has ethical approval granted by the Black Country National Health Service Research Ethics Committee (14/WM/1220). Results of this trial will be submitted for publication in peer-reviewed journals and presented at conferences. The study is being conducted according to the principles of the Declaration of Helsinki.Trial registration numberNCT02467153; Post-results.

Aims To establish the prevalence of admission plasma glucose in 'diabetes' and 'at risk' ranges in emergency hospital admissions with no prior diagnosis of diabetes; characteristics of people with hyperglycaemia; and factors influencing glucose measurement. Methods Electronic patient records for 113 097 hospital admissions over 1 year from 2014 to 2015 included 43 201 emergencies with glucose available for 31 927 (74%) admissions, comprising 22 045 people. Data are presented for 18 965 people with no prior diagnosis of diabetes and glucose available on first attendance. Results Three quarters (14 214) were White Europeans aged 62 (43‐78) years, median (IQ range); 12% (2241) South Asians 46 (32‐64) years; 9% (1726) Unknown/Other ethnicities 43 (29‐61) years; and 4% (784) Afro‐Caribbeans 49 (33‐63) years, P 24 hours. Conclusions Hyperglycaemia was evident in 21% of adults admitted as an emergency; various aspects related to follow‐up and initial testing, age and ethnicity need to be considered by professional bodies addressing undiagnosed diabetes in hospital admissions., Glucose needs to be measured in all adults admitted as an emergency not just those over 40/30 years old, as younger people particularly South Asians and Afro‐Caribbeans are at risk of being admitted with undiagnosed diabetes. Overall, 5% of emergency admissions had glucose in the ‘diabetes’ range, 8% if South Asian and Afro‐Caribbean, with 16% of people in the ‘at risk’ range. One third of all emergency admissions were for 24 hours.

Objectives To estimate the cumulative effective dose of radiation (E) and additional lifetime attributable risk (LAR) of cancer from ionizing radiation in children with osteogenesis imperfecta (OI), who require frequent imaging for fractures and bone densitometry (DXA) surveillance. Also, to evaluate the pattern of long bone fractures. Methods We reviewed all imaging (x-rays, DXA and computed tomography [CT]) conducted in a cohort of children with OI with a minimum observation period of 5 years. For each image, E was estimated using age-dependent local data, and LAR of cancer was extrapolated. LAR and fracture data were compared among children with mild, moderate and severe OI. LAR was allocated to cancer risk categories, and the moderate risk group (1 in 1000 to 1 in 100) was evaluated further. Results Results from 106 children with OI (50% females, 5747 images) are presented, with a median (range) observation period of 11.7 (5.2–15.6) years. CT accounted for 0.8% of total imaging procedures but contributed to 66% of total E. The overall LAR of cancer was minimal, averaging an additional 8.8 cases per 100,000 exposed patients (0.8–403). LAR was significantly lower in children with mild OI compared to those with moderate (p = 0.006) and severe OI (p = 0.001). All patients with a moderate LAR of cancer (n = 8) had undergone CT scans and 88% had scoliosis or vertebral fractures. The cohort experienced 412 long bone fractures, with the most common site being the femur (26.5%). OI severity correlated positively with long bone fracture rates (p Conclusions When compared to baseline LAR of cancer (50%) the additional cancer risk from ionizing radiation imaging in our paediatric OI cohort was small (0.0088%). To reduce additional cancer risk, we recommend replacing spinal x-rays with vertebral fracture assessments on DXA and exercising caution with CT imaging.

Aims: The National Institute for Health and Care Excellence (NICE) recommendation for insulin in newly diagnosed type 1 diabetes is a ‘basal-bolus’ regimen of prandial insulin with twice-daily basal insulin initiated at diagnosis. We developed an insulin initiation programme that embraces the contribution of endogenous insulin to glycaemic control in adults newly diagnosed with type 1 diabetes. Our aim was to embed carbohydrate counting skills and dose adjustment very early on to mitigate against the decline in glycaemic control that is commonly seen post honeymoon.Methods: We designed a novel insulin initiation programme that focused initially on prandial insulin replacement using the lowest possible dose of basal insulin. The approach also facilitates carbohydrate counting and bolus insulin dose adjustment behaviours from diagnosis.Results: Prior to implementing the new programme, the mean HbA1c at 12 months was 64 mmol/mol (8.0%) (95% CI 60 to 69 (7.6% to 8.4%)). This reduced to 55 mmol/mol (7.1%) (95% CI 51 to 58 (6.9% to 7.4%)), p

This study aimed to evaluate the prevalence of glucocorticoid-induced adrenal insufficiency in a cohort of patients with brain and skull base tumours and to identify factors which may predict its occurrence. Patients with brain or skull base tumours attending for a short synacthen test (SST) (adrenocorticotropin hormone (ACTH) stimulation test) at a single institution over a 3-year period were retrospectively identified. Baseline demographics and dexamethasone exposure were examined. Only patients with dexamethasone exposure were included in the final analysis looking at the primary end point of SST failure. Fisher’s exact test, Student’s t test, Mann-Whitney test and the Kendall’s tau-b test were used to evaluate the influence of age, gender, diagnosis and mean pituitary radiation dose on the primary endpoint. Receiver operating characteristic (ROC) curves were generated to explore the impact of duration and total exposure to dexamethasone on likelihood of SST failure. Thirty-one of 51 patients with previous dexamethasone exposure failed their first SST (61%). No significant relationship was demonstrated between age, gender, diagnosis or mean pituitary radiation dose and SST failure. Duration of and total exposure to dexamethasone were significantly associated with SST failure (p = 0.001 and p = 0.007, respectively). ROC curves generated values of 78 days and 171 mg days to give a sensitivity of 94 and 97%, respectively, to detect SST failure. Duration of dexamethasone use and total exposure predict for adrenal insufficiency in patients with brain and skull base tumours. Values derived from this study may be useful to identify patients at higher risk of adrenal suppression who require empirical hydrocortisone pending formal testing of the hypothalamic-pituitary-adrenal axis.

Background:First-degree relatives (FDRs) of patients with rheumatoid arthritis (RA) are at increased risk of RA and are being recruited to studies of predictive and preventive approaches. Access to FDRs is usually via the proband with RA. Qualitative investigations have shown that communication of RA risk to FDRs is a complex and selective process. However, quantitative data are needed to develop a robust understanding of this process and its determinants to develop effective communication strategies and support for RA patients and their relatives.Objectives:To identify predictors of the RA patients’ reported likelihood of communicating RA risk information to their FDRs.Methods:Patients with RA were invited to anonymously complete a survey assessing patient characteristics including age, gender, duration of RA, information seeking and decision making preferences (Autonomy Preference Index1), interest in FDRs taking a predictive test for RA, dispositional openness, and the general functioning subscale of the McMaster Family Assessment Device2. Reported likelihood of communicating RA risk to each of the patients’ FDRs was assessed using a Likert scale ranging from extremely unlikely (0) to extremely likely (4). The median score across all FDRs was calculated for each patient. The association between patient characteristics and the median score was examined using univariate approaches.Results:Surveys were completed by 482 patients (median age 65 years, 72% female). Most patients reported being likely to communicate RA risk to their FDRs (median score=3). Those who reported their likelihood of communicating RA risk to both children and siblings were more likely to communicate risk to children than siblings (p<0.001). No significant difference was found for FDRs’ gender, or patients’ gender, on reported likelihood to communicate about RA risk (p=0.32 and p=0.87, respectively). Patients who were older and who had had RA for longer were less likely to communicate about RA risk with their relatives. Patients who had higher interest in their FDRs taking a predictive test for RA, information seeking preferences, openness to communicate, and family functioning were more likely to communicate about risk (Table 1).Table 1.Descriptive statistics and Spearman’s rank-order correlations for the association between patients’ characteristics and their median reported likelihood of communicating to their FDRs about RA riskPatient characteristicsDescriptive statisticsAssociation with median likelihood to communicate risk to relativesTest statisticP valueAge; median (IQR)65 (55-72)-0.19RA duration; median (IQR)10 (4-20)-0.180.001*Autonomy preferences Information seeking; median (IQR)84 (75-97)0.26 Decision making; median (IQR)54 (42-67)0.090.048Interest in children taking a test; median (IQR)3 (2-3)0.44Interest in siblings taking a test; median (IQR)2 (2-3)0.44Openness; median (IQR)2 (1-3)0.130.004*Family functioning; median (IQR)2 (2-3)0.23* p values significant at the Bonferroni adjusted value of 0.006.Conclusion:Respondents were willing to communicate RA risk to their FDRs, and were more likely to communicate about risk to their children than their siblings. Factors including information seeking preferences, dispositional openness, interest in FDRs taking a predictive test, and family functioning were associated with increased likelihood of communicating RA risk information to FDRs. Patients’ age and RA duration were associated with decreased likelihood. These findings increase understanding of communication about RA risk in families, and will inform the development of informational approaches to support family communication and access to FDRs.References:[1]Ende et al. Journal of General Internal Medicine. 1989; 4(1): 23-30.[2]Epstein et al. Journal of Marital and Family therapy.1983; 9(2): 171-180.Acknowledgements:This work was supported by Versus Arthritis; Grant reference: 21560 and Riksbankens Jubileumsfond (The Swedish Foundation for Humanities and Social Sciences); Grant reference: M13-0260:1 ‘Mind the Risk’.Disclosure of Interests:Imogen Wells: None declared, Peter Nightingale: None declared, Gwenda Simons: None declared, Christian Mallen Grant/research support from: Keele School of Medicine have received funding to support BMS recruit to a non-pharmacological atrial fibrillation trial., Karim Raza Grant/research support from: KR reports grants from Abbvie and Pfizer, and personal fees from Abbvie, Pfizer, Sanofi, Lilly, Bristol Myers Squibb, UCB, Janssen, and Roche Chugai, all outside the submitted work., M. Falahee: None declared

Dysregulated neutrophil functions with age and sepsis are described. Statins are associated with improved infection survival in some observational studies, but trials in critically ill patients have not shown benefit. Statins also alter neutrophil responses in vitro.To assess neutrophil migratory accuracy with age during respiratory infections and determine if and how a statin intervention could alter these blunted responses.The migratory accuracy of blood neutrophils from young (aged35 yr) and old (aged60 yr) patients in health and during a lower respiratory tract infection, community-acquired pneumonia, and pneumonia associated with sepsis was assessed with and without simvastatin. In vitro results were confirmed in a double-blind randomized clinical trial in healthy elders. Cell adhesion markers were assessed.In vitro neutrophil migratory accuracy in the elderly deteriorated as the severity of the infectious pulmonary insult increased, without recovery at 6 weeks. Simvastatin rescued neutrophil migration with age and during mild to moderate infection, at high dose in older adults, but not during more severe sepsis. Confirming in vitro results, high-dose (80-mg) simvastatin improved neutrophil migratory accuracy without impeding other neutrophil functions in a double-blind randomized clinical trial in healthy elders. Simvastatin modified surface adhesion molecule expression and activity, facilitating accurate migration in the elderly.Infections in older adults are associated with prolonged, impaired neutrophil migration, potentially contributing to poor outcomes. Statins improve neutrophil migration in vivo in health and in vitro in milder infective events, but not in severe sepsis, supporting their potential utility as an early intervention during pulmonary infections. Clinical trial registered with www.clinicaltrialsregister.eu (2011-002082-38).

Community-acquired pneumonia (CAP) is the leading cause of death from infection in developed countries. There is evidence of an association between improved survival from infection and statin use. The possible beneficial effects of statins are complicated by the common use of macrolide antibiotics for pneumonia, with current guidance suggesting that concurrent macrolide and statin use is contraindicated.We conducted an observational study of statin use in patients with CAP. Of 2,067 patients with CAP, 30.4% were on statin therapy at admission. Statin users were more likely to survive the admission (p

Background Acute Kidney Injury (AKI) has evoked much interest over the past decade and is reported to be associated with high inpatient mortality. Preventable death and increased readmission rates related to AKI have been the focus of considerable interest. Methods We studied hospital acquired AKI in all emergency hospital admissions, except transfers from ICU to ICU or patients known to renal services, to ascertain mortality and readmission rates, and trackable modifiable factors for death, using cox regression and Kaplan Meier survival curves. Data was extracted from the electronic patient records and a series of case notes reviewed. Admissions were included between April 2006 and March 2010 (and patients followed up until September 2011). Results Overall incidence of AKI was 2.2%, (AKI stage 1, 61%, stage 2,27% and stage 3, 12%). In patients who sustain in-hospital AKI, 34% die in hospital, 42% are dead at 90 days and 48% at 1 year post discharge, compared to 12% 1 year mortality in patients without AKI. In multivariable analyses, AKI is an independent risk factor for in-hospital mortality (Hazard Ratio 1.6: 95% confidence intervals 1.43–1.75: P

Aim To estimate the proportion of type 2 diabetes mellitus and abnormal glucose homeostasis in childhood obesity and assess the predictive role of HbA1c as a diagnostic marker compared with oral glucose tolerance testing (OGTT). Methods A retrospective study in a tertiary paediatric hospital. Data were collected on all overweight or obese children who underwent routine OGTT between 2012 and 2016. Ethnicity, anthropometry, comorbidities and other risk factors associated with diabetes were recorded systematically. Fasting venous glucose, insulin and HbA1c values, along with 120-min venous glucose were recorded. Receiver operating characteristic (ROC) curve analysis was performed to derive optimum thresholds of HbA1c for detection of type 2 diabetes, impaired fasting glucose (IFG) and impaired glucose tolerance (IGT). Predictive HbA1c thresholds for the detection of abnormal glucose homeostasis in children with obesity were calculated. Results Of 156 children, 13 (8%, 10 female, 10 Asian) had type 2 diabetes, 95 (61%) had normal glucose tolerance, 18 (12%) had isolated IFG, 19 (12%) had isolated IGT, and another 11 (7%) had both IFG and IGT. The proportion of abnormal glucose homeostasis was 39%. ROC curve analysis demonstrated that HbA1c ≥ 42 mmol/mol (6.0%) predicted type 2 diabetes (specificity 95%, sensitivity 85%) but performed moderately for IFG (specificity 46%, sensitivity 78%) and IGT (specificity 78%, sensitivity 55%). Conclusion Despite HbA1c being a less-sensitive diagnostic tool compared with OGTT for children with IFG and IGT, it is reliable in detecting type 2 diabetes in asymptomatic children with obesity, instead of the labour- and cost-intensive OGTT.

Introduction Pirfenidone and nintedanib are the only disease-modifying treatments available for idiopathic pulmonary fibrosis (IPF). Clinical trials have demonstrated a disease-stabilising effect of these medications in controlled conditions. Our aim was to test their efficacy, tolerability and safety in routine clinical practice. Methods Data was collected retrospectively on patients with IPF seen in the ILD MDT between 2011–2017. This included patients treated with antifibrotics and those untreated, but with an FVC% predicted in the treatment range (control patients). Variables collected from the electronic patient records included demographics, lung function, survival, progression-free survival (PFS) – progression defined as 10% reduction in FVC or death – and drug tolerability outcomes including discontinuations. Results Of 104 patients prescribed antifibrotics, 54 received pirfenidone only, 36 received nintedanib only and 14 received both. There were 64 control patients. The 365-day mortality rate was 25.3% for the antifibrotic group and 35.5% for the control group (p=0.169). PFS at 6 months was significantly improved in the antifibrotic group (73.7%) compared to the control group (54.8%) (p=0.015). At 12 months, PFS was improved in the antifibrotic group (49.5% in the antifibrotic group and 37.1% in the control group), although the result was not statistically significant (p=0.127). The 12-month post-treatment mean decline in FVC% predicted (4.8±6.7%) was significantly less than the 12-month pre-treatment decline (11.7±12.2%) (p=0.041). Antifibrotic discontinuation by 3 months was significantly higher for patients on pirfenidone (31.7%) than those on nintedanib (11.4%) (p=0.026). By 12 months, discontinuation was higher in the pirfenidone group (48.3%) than the nintedanib group (40%) but the difference was not statistically significant (p=0.431). The 365-day mortality rate for the antifibrotic group, excluding patients who discontinued treatment within 3 months, was 20.3% and the difference between this and the control group (35.5%) was statistically significant (p=0.043). Conclusion Promising results were shown for mortality, PFS and lung function for patients on antifibrotics, although this data may favour commencement of nintedanib as first line therapy, given the lower rates of treatment discontinuation by 3 months. Patients who were able to tolerate antifibrotic therapy for the first 3 months were shown to have a significantly improved mortality.

Background. The long-term use of calcineurin inhibitors (CNIs) after liver transplantation (LT) is associated with nephrotoxicity. Methods. Five-year follow-up data were retrieved from the randomized controlled multicenter SiLVER trial. Standard CNI-based mammalian target of rapamycin-free immunosuppression (group A, n = 264) was compared with a 50% reduction of CNI and introduction of the mammalian target of rapamycin inhibitor Sirolimus (SIR) within 4-6 weeks after LT (group B, n = 261). Results. Median MELD at LT was low with 10 (7-15) (group A) and 11 (8-15) (group B) in the intention-to-treat approach. CNI dose and CNI trough were reduced by 20% and 8% (group A) versus 55% and 56% (group B) at 3 months posttransplantation. Renal function was preserved at 3 months after LT in the SIR arm (estimated glomerular filtration rate 74 [57-95] versus 67 [55-85] mL/min/1.73m2 P = 0.004) but was similarly impaired thereafter compared with group A. The per protocol analysis identified LT recipients in group B with concomitant early CNI minimization and SIR treatment >= year 1 with significantly superior estimated glomerular filtration rate and lowest rate of chronic kidney disease (>= stage 3) from year 1 onwards until study end. Competing risk factors for renal disease (arterial hypertension, fat metabolism disorder, and hyperglycemia) were not associated with worse kidney function. Conclusions. Prevention of CNI nephrotoxicity by SIR-based early CNI minimization protects renal function only short-term after LT in the intention-to-treat analysis of this low MELD cohort. Yet, selected LT recipients compliant with early CNI minimization and SIR maintenance achieved better long-term renal outcomes compared with real-world practice.

Objectives: Tunnelled central venous catheters dysfunction can be defined as failure to provide blood flow above 200 mL/min during dialysis often caused by thrombosis. Although urokinase is used routinely for thrombolysis, there is wide variation in dose regimens. A multidisciplinary group was formed to address this issue and offer guidance. Methods: Dialysis centres that used urokinase in the United Kingdom took part in a prospective study to determine the safety and outcomes of thrombolysis using agreed protocols. Data were collected anonymously from September 2017 until February 2018. Catheter blood flow was measured before and after the following interventions: catheter dwell or push locks with 12,500–50,000 IU or catheter infusion with 100,000–250,000 IU of urokinase. Interventions were repeated if the blood flow remained below 200 mL/min. Results: 10 centres took part and recruited 200 patients; 45.5% were female and 54.5% were male with mean age of 63.6 (±15.2) years. The cumulative success rate for thrombolysis was 90.5% after first intervention, 97% after second intervention, and 99% after more than 2 interventions. Although there was trend towards benefit with dose increments, the success rate between push/dwell locks and high-dose infusion of urokinase was not significantly different (p = 0.069). Seventeen (8.5%) tunnelled central venous catheters were removed due to failure of treatment. No urokinase-related adverse events were reported. Conclusion: In this study, urokinase was safe and efficacious; there was no difference between dwell and push locks. There was some benefit with high-dose infusion of urokinase compared to the dwell and push lock.

Objective: Glucose is measured on hospital admission as an emergency as elevated glucose is associated with an eight-fold risk of dying in hospital. This study reports on admission plasma glucose by ethnicity in people without prior diabetes. Research Design and Methods: A clinical audit CARMS-12031 of electronic patient records for 113,097 admissions to hospital over 1 year from April 2014 to March 2015 identified 43,201 emergency admissions with glucose unavailable for 11,274 (26%). Of 5,867 admissions with prior diabetes coding, 5,523 (94%) had glucose recorded. First attendances were analyzed for emergency admissions with no record of diabetes. Results: Of these 18,965 people admitted, 75% were White Europeans WE who were older than South Asians SA 12%, unknown/other ethnic groups U 9%, and Afro-Caribbeans AC 4%. 1,003 people admitted as an emergency had glucose in ‘diabetes range’ (≥11.1mmol/L) and 3,042 in ‘at risk’ range (7.8 to 11.0mmol/L). More SA 8% had glucose in diabetes range than WE 5% and also than U 5%; there were significantly more WE 17% in ‘at risk’ range than U 14% or AC 11%. Higher glucose was observed in SA and U men than women, p = 0.005 and p = 0.018, respectively. Conclusions: Protocols should target people requiring additional HbA1c testingto diagnose undiagnosed diabetes on hospital admission especially younger SA and AC individuals, and outline appropriate clinical intervention. Disclosure S. Ghosh: Advisory Panel; Self; Abbott. Other Relationship; Self; Mylan. R. Susarla: None. R.A. Round: None. P. Nightingale: None. J.A. Williams: None. I.M. Stratton: Consultant; Self; Novo Nordisk A/S. Research Support; Self; Bayer AG, Boehringer Ingelheim International GmbH. G. Gkoutos: None. J. Webber: None. W. Hanif: Advisory Panel; Self; Boehringer Ingelheim International GmbH. Consultant; Self; Novo Nordisk A/S. Research Support; Self; AstraZeneca, Janssen Diagnostics, Sanofi. Speaker's Bureau; Self; AstraZeneca, Novartis AG, Novo Nordisk A/S. G. Roberts: None. S.E. Manley: None.

Introduction: As HbA1c is now widely used for the diagnosis of diabetes with WHO cut-off ≥ 48 mmol/mol/6.5%, it is debatable whether the value should vary by ethnicity. Aim: This study compares plasma glucose and HbA1c in white European WE, South Asian SA, unknown/other U and Afro-Caribbean AC people admitted as an emergency. Methods: Electronic patient records were interrogated over 1 year (2014/5) for a clinical audit, CARMS-12031R. Glucose was measured on wards with meters/gas machines or the laboratory along with HbA1c on Tosoh G8 HPLC analysers if haemoglobin normal. Results: There were 30,664 people of whom 22,045 (72%) had glucose recorded and 2,083 (7%) HbA1c. 1,904 (6%) had both glycaemic markers and were aged 64 (50-78) years, median (IQ range); 839 (44%) female; 560 (29%) prior diabetes diagnosis; 1,405 (74%) WE, 296 (16%) SA, 112 (6%) U and 91 (5%) AC. Glucose was 7.4 (5.8-10.6), 8.6 (6.2-12.3), 8.1 (5.9-10.7), 7.0 (5.9-11.6) mmol/L and HbA1c 42 (37-55), 50 (41-70), 42 (38-60), 46 (39-70) mmol/mol/6.0 (5.5-7.2), 6.7 (5.9-8.6), 6.0 (5.6-7.6), 6.4 (5.7-8.6)%, respectively. HbA1c was higher relative to glucose in SA and AC compared to WE and U, p Conclusions: Haematological differences related to red blood cell turnover may account for the variance; this should be recognised by those involved in producing protocols/guidelines for diagnosis. More research is required on using HbA1c to confirm undiagnosed diabetes in admissions. Disclosure S.E. Manley: None. R. Susarla: None. R.A. Round: None. P. Nightingale: None. J.A. Williams: None. I.M. Stratton: Consultant; Self; Novo Nordisk A/S. Research Support; Self; Bayer AG, Boehringer Ingelheim International GmbH. J. Webber: None. G. Gkoutos: None. W. Hanif: Advisory Panel; Self; Boehringer Ingelheim International GmbH. Consultant; Self; Novo Nordisk A/S. Research Support; Self; AstraZeneca, Janssen Diagnostics, Sanofi. Speaker's Bureau; Self; AstraZeneca, Novartis AG, Novo Nordisk A/S. G. Roberts: None. S. Ghosh: Advisory Panel; Self; Abbott. Other Relationship; Self; Mylan.

BackgroundCommunity-acquired pneumonia (CAP) is a leading cause of sepsis worldwide. Prompt identification of those at high risk of adverse outcomes improves survival by enabling early escalation of care. There are multiple severity assessment tools recommended for risk stratification; however, there is no consensus as to which tool should be used for those with CAP. We sought to assess whether pneumonia-specific, generic sepsis or early warning scores were most accurate at predicting adverse outcomes.MethodsWe performed a retrospective analysis of all cases of CAP admitted to a large, adult tertiary hospital in the UK between October 2014 and January 2016. All cases of CAP were eligible for inclusion and were reviewed by a senior respiratory physician to confirm the diagnosis. The association between the CURB65, Lac-CURB-65, quick Sequential (Sepsis-related) Organ Failure Assessment tool (qSOFA) score and National Early Warning Score (NEWS) at the time of admission and outcome measures including intensive care admission, length of hospital stay, in-hospital, 30-day, 90-day and 365-day all-cause mortality was assessed.Results1545 cases were included with 30-day mortality of 19%. Increasing score was significantly associated with increased risk of poor outcomes for all four tools. Overall accuracy assessed by receiver operating characteristic curve analysis was significantly greater for the CURB65 and Lac-CURB-65 scores than qSOFA. At admission, a CURB65 ≥2, Lac-CURB-65 ≥moderate, qSOFA ≥2 and NEWS ≥medium identified 85.0%, 96.4%, 40.3% and 79.0% of those who died within 30 days, respectively. A Lac-CURB-65 ≥moderate had the highest negative predictive value: 95.6%.ConclusionAll four scoring systems can stratify according to increasing risk in CAP; however, when a confident diagnosis of pneumonia can be made, these data support the use of pneumonia-specific tools rather than generic sepsis or early warning scores.

ObjectiveTo investigate delays from symptom onset to rheumatology assessment for patients with a new onset of rheumatoid arthritis (RA) or unclassified arthritis.MethodsNewly presenting adults with either RA or unclassified arthritis were recruited from rheumatology clinics. Data on the length of time between symptom onset and first seeing a GP (patient delay), between first seeing a general practitioner (GP) and being referred to a rheumatologist (general practitioner delay) and being seen by a rheumatologist following referral (hospital delay) were captured.Results822 patients participated (563 female, mean age 55 years). The median time between symptom onset and seeing a rheumatologist was 27.2 weeks (IQR 14.1–66 weeks); only 20% of patients were seen within the first 3 months following symptom onset. The median patient delay was 5.4 weeks (IQR 1.4–26.3 weeks). Patients who purchased over-the-counter medications or used ice/heat packs took longer to seek help than those who did not. In addition, those with a palindromic or an insidious symptom onset delayed for longer than those with a non-palindromic or acute onset. The median general practitioner delay was 6.9 weeks (IQR 2.3–20.3 weeks). Patients made a mean of 4 GP visits before being referred. The median hospital delay was 4.7 weeks (IQR 2.9–7.5 weeks).ConclusionThis study identified delays at all levels in the pathway towards assessment by a rheumatologist. However, delays in primary care were particularly long. Patient delay was driven by the nature of symptom onset. Complex multi-faceted interventions to promote rapid help seeking and to facilitate prompt onward referral from primary care should be developed.

Background Intravenous pulse methylprednisolone (MP) is commonly included in the management of severe ANCA associated vasculitis (AAV) despite limited evidence of benefit. We aimed to evaluate outcomes in patients who had, or had not received MP, along with standard therapy for remission induction in severe AAV. Methods We retrospectively studied 114 consecutive patients from five centres in Europe and the United States with a new diagnosis of severe AAV (creatinine > 500 μmol/L or dialysis dependency) and that received standard therapy (plasma exchange, cyclophosphamide and high-dose oral corticosteroids) for remission induction with or without pulse MP between 2000 and 2013. We evaluated survival, renal recovery, relapses, and adverse events over the first 12 months. Results Fifty-two patients received pulse MP in addition to standard therapy compared to 62 patients that did not. There was no difference in survival, renal recovery or relapses. Treatment with MP associated with higher risk of infection during the first 3 months (hazard ratio (HR) 2.7, 95%CI [1.4–5.3], p = 0.004) and higher incidence of diabetes (HR 6.33 [1.94–20.63], p = 0.002), after adjustment for confounding factors. Conclusions The results of this study suggest that addition of pulse intravenous MP to standard therapy for remission induction in severe AAV may not confer clinical benefit and may be associated with more episodes of infection and higher incidence of diabetes. Electronic supplementary material The online version of this article (10.1186/s12882-019-1226-0) contains supplementary material, which is available to authorized users.

Varying rates of oesophageal adenocarcinoma (OAC) complicating Barrett's oesophagus (BO) have been reported. Recent studies and meta-analyses suggest a lower incidence, questioning the value of endoscopic surveillance.We aimed to retrospectively examine the rate of OAC, risk factors and causes of death in a prospectively recruited BO cohort.Data from patients with BO from a cohort from 1982-2007 were studied. Patients were subdivided into surveyed, failed to attend surveillance and unfit for surveillance. Standardised mortality ratios (SMR) were calculated for common causes of death. Cox proportional hazards models were used to determine which factors were associated with progression to OAC.In total, 671 BO patients (61% male) were studied; 37 (76% male) were diagnosed with OAC. OAC incidence was 0.47% per annum and stable across three decades (1982-1991 0.56%, 1992-2001 0.46%, 2002-2012 0.41% (Progression to OAC appeared stable over three decades at 0.47% per annum. Patients with BO had a modest increase in all-cause mortality and a large increase in OAC mortality, particularly if fit for surveillance. Low-grade dysplasia and the length of the BO segment were associated with developing OAC.

Objective: This study investigated differences in cardiorespiratory fitness, muscular function, perceived exertion, and anxiety/depression between patients and healthy controls (HCs) and assessed which of these variables may account for the fatigue experienced by patients. Methods: Fatigue was measured in 48 antineutrophil cytoplasmic antibody–associated vasculitis patients and 41 healthy controls using the Multidimensional Fatigue Inventory (MFI‐20), focusing on the physical component. Quality of life, anxiety/depression, and sleep quality were assessed by validated questionnaires. Muscle mass was measured by dual‐energy x‐ray absorptiometry scan, strength as the maximal voluntary contraction (MVC) force, and endurance as sustained isometric contraction at 50% MVC of the quadriceps. Voluntary activation was assessed by superimposed electrical stimulation. Cardiorespiratory fitness ( urn:x-wiley:00431397:media:acr22827:acr22827-math-0010 and oxygen pulse [O2 pulse]) and perceived exertion (Borg scale) were measured during progressive submaximal exercise. Results: Patients reported elevated physical fatigue scores compared to HCs (patients MFI‐20 physical 13 [interquartile range (IQR) 8–16], HCs MFI‐20 physical 5.5 [IQR 4–8]; P

NHS staff with vitamin D deficiency were more likely to have developed COVID-19, with staff from BAME ethnicity being the most vitamin D deficient.

BackgroundStudies suggest that certain Black and Asian Minority Ethnic groups experience poorer outcomes from COVID-19 but these studies have not provided insight into potential reasons for this. We hypothesised that outcomes would be poorer for those of South Asian ethnicity hospitalised from a confirmed SARS-CoV-2 infection, once confounding factors, health seeking behaviours and community demographics were considered and that this might reflect a more aggressive disease course in these patients.MethodsPatients with confirmed SARS-CoV-2 infection requiring admission to University Hospitals Birmingham NHS Foundation Trust(UHB) in Birmingham UK between 10thMarch 2020-17thApril 2020 were included. Standardised Admission Ratio(SAR) and Standardised Mortality Ratio(SMR) were calculated using observed COVID-19 admissions/deaths and 2011 census data. Hazard Ratio (aHR) for mortality was estimated using Cox proportional hazard model adjusting and propensity score matching.ResultsAll patients admitted to UHB with COVID-19 during the study period were included (2217 in total). Fifty-eight percent were male, 69.5% White and the majority (80.2%) had co-morbidities. Eighteen and a half percent were of South Asian ethnicity, and these patients were more likely to be younger, have no co-morbidities but twice the prevalence of diabetes than White patients. SAR and SMR suggested more admissions and deaths in South Asian patients than would be predicted and they were more likely to present with severe disease despite no delay in presentation since symptom onset. South Asian ethnicity was associated with an increased risk of death; both by Cox regression (Hazard Ratio 1.4 (95%CI 1.2–1.8) after adjusting for age, sex, deprivation and comorbidities and by propensity score matching, matching for the same factors but categorising ethnicity into South Asian or not (Hazard ratio 1.3 (1.0-1.6)).ConclusionsThose of South Asian ethnicity appear at risk of worse COVID-19 outcomes, further studies need to establish the underlying mechanistic pathways.

Introduction and objectives Community acquired pneumonia (CAP) is a leading cause of death worldwide. Early recognition of patients with CAP at risk of poor outcomes improves survival. Identification of factors independently associated with poor outcomes could inform the design of novel strategies for detecting those patients at risk of decline. We retrospectively collected data on patients with CAP in order to ascertain which physiological, biochemical and haematological parameters at the point of admission are independently associated with 30 day mortality. Methods Adults admitted to a large tertiary centre hospital, with CAP, between 10/2014 and 01/2016 were included. Radiology, admission clerkings and electronic patient records were reviewed to confirm pneumonia and collect comorbidity, observation and laboratory investigation data from the point of presentation to hospital. Cases were excluded if there was no radiological confirmation of CAP, or if they had hospital-acquired pneumonia. Optimal cut-off points were calculated for continuous variables, and univariate analysis performed to identify factors associated with 30 day mortality. Those found to be associated were then included in a multivariate logistic regression analysis to identify those independently associated with 30 day mortality. Statistical significance was pre-defined with a p value Results 1545 patients were included in the final analysis (median age 76, 30 day mortality 19.0%, 49.2% female). Univariate analysis identified age, aetiology, tachypnoea, hypotension, need for supplementary oxygen, hypothermia/hyperthermia, tachycardia, confusion, uraemia, elevated creatinine, hypoproteinaemia, hypoalbuminaemia, anaemia, neutrophilia, lymphopaenia/lymphocytosis, raised neutrophil-lymphocyte ratio, raised CRP, acidosis, hyperlactataemia, dementia, cerebrovascular disease, solid tumour malignancy and haematological diagnosis as associated with increased risk of 30 day mortality. Following stepwise, forward, logistic regression analysis, factors independently associated with 30 day mortality included age, tachypnoea, need for supplementary oxygen, hypothermia, uraemia, hypoalbuminaemia, high neutrophil-lymphocyte ratio, acidosis, hyperlactataemia and solid tumour malignancy. Presence of metabolic disease (obesity and dyslipidaemia) had a protective effect (table 1). There was no evidence of co-linearity between these variables. Conclusions We present factors independently associated with 30 day mortality in a large cohort of CAP patients. This analysis may be helpful to inform the creation of novel severity assessment tools for CAP.

BACKGROUND Cardiac dysfunction is frequently observed in patients with cirrhosis. There remains a paucity of data from routine clinical practice regarding the role of echocardiography in the pre-assessment of transjugular intrahepatic portosystemic stent-shunt. AIM Our study aimed to investigate if echocardiography parameters predict outcomes after transjugular intrahepatic portosystemic stent-shunt insertion in cirrhosis. METHODS Patients who underwent echocardiography and transjugular intrahepatic portosystemic stent-shunt insertion at the liver unit (Birmingham, UK) between 1999 and 2016 were included. All echocardiography measures (including left ventricle ejection fraction; early maximal ventricular filling/late filling velocity ratio, diastolic dysfunction as per British Society of Echocardiography guidelines) were independently reviewed by a cardiologist. Predictors of 30-day and overall transplant free-survival were assessed. RESULTS One Hundred and Seventeen patients with cirrhosis (median age 56 years; 54% alcohol; Child-Pugh B/C 71/14.5%; Model For End-Stage Liver Disease 12) underwent transjugular intrahepatic portosystemic stent-shunt for ascites (n = 78) and variceal haemorrhage (n = 39). Thirty-day and overall transplant-free survival was 90% (n = 105) and 31% (n = 36), respectively, over a median 663 (IQR 385-2368) days follow-up. Model for End-Stage Liver Disease (P

Stereotactic radiosurgery (SRS) and radiotherapy (SRT) are considered standard of care for patients with 1–3 brain metastases with favourable prognosis. The role of SRS/SRT for multiple metastases remains debated. This project evaluated SRS/SRT outcomes when treating 4 or more brain metastases up to a maximum volume of 20cc. METHODS: Treatment episodes for patients with 4 or more brain metastases were identified from a single centre prospective database from August 2013 to October 2017. All patients were WHO PS 0–1 and treated using Cyberknife. Target volumes were neuroradiology approved with no additional margin beyond the enhancing volume. A retrospective review of electronic records and imaging was undertaken. Overall survival (OS) and distant brain recurrence free survival were calculated using Kaplan-Meier method from the date of treatment, censoring at last clinic visit or MRI respectively. RESULTS: 69 episodes (61 SRS, 7 SRT) were identified with a total of 458 metastases. Primary sites were melanoma (31.9%), lung (29%), breast (27.5%), renal (5.8%), other (5.7%). Median number of targets per episode was 5 (range 4–36). Median SRS dose was 21Gy (range 15-24Gy). Median SRT dose was 24Gy in 3 fractions (range 17.7/3#-27/3#). Median OS was 9.4 months (95% CI 6.5–12.4 months). In patients 65 years (p65 years(p=0.001). Median OS was 14 months for breast cancer versus 8.4 months for other primary sites (p=0.094). Number of metastases was not predictive of OS or occurrence of distant brain metastases. DISCUSSION: Data supports the ongoing use of volume rather than number of metastases alongside established prognostic factors including age when selecting patients for SRS/SRT.

Background There is a need for a large, contemporary, multi-centre series of measured glomerular filtration rates (mGFR) from healthy individuals to determine age- and gender-specific reference ranges for GFR. We aimed to address this and to use the ranges to provide age- and gender-specific advisory GFR thresholds considered acceptable for living kidney donation. Methods Individual-level data including pre-donation mGFR from 2974 prospective living kidney donors from 18 UK renal centres performed between 2003 and 2015 were amalgamated. Age- and gender-specific GFR reference ranges were determined by segmented multiple linear regression and presented as means ± two standard deviations. Results Males had a higher GFR than females (92.0 vs 88.1 mL/min/1.73m2, P 60 years had a GFR

Advance care planning (ACP) is becoming more widely used as part of a drive to improve personalized care planning, but there is still more work to be done. Electronic Palliative Care Co-ordination systems (EPaCCs) have proved to be very effective in some areas but there are many barriers to be overcome before they are universally available. This chapter covers recent developments leading to the wider integration of ACP into primary care. These include policy initiatives, educational opportunities, information technology (IT), professional quality control and regulation, financial and business incentives, and the Compassionate Community movement. The chapter includes an overview of issues surrounding ACP in primary care and in the community.

BACKGROUND The impact of ethnicity on outcomes after orthotopic liver transplantation (OLT) is unclear. The British Indo-Asian population has a high incidence of liver disease but its contribution to the national deceased donor pool is small. We evaluated access to and outcomes of OLT in Indo-Asians. METHODS We compared 182 Indo-Asians with white patients undergoing OLT. Matching criteria were transplantation year, liver disease, age, sex. Donor and recipient characteristics, postoperative outcomes, including patient and graft survival, OLT era (early, 1987-2001; late, 2002-2011) were compared. Survival was also analyzed by underlying disease-acute liver failure (ALF) and chronic liver failure. RESULTS Indo-Asians had higher diabetes incidence. There were no differences in waiting time for transplantation, despite smaller body size and more uncommon blood groups (B, AB) among Indo-Asians. In the early era, patient survival for Indo-Asians with ALF was worse when compared to whites. In the late era, graft and patient survival at 1, 2, and 5 years were similar between groups. CONCLUSION This study demonstrates that Indo-Asian patients have equal access to OLT and comparable outcomes to whites in the United Kingdom. Survival has improved among Indo-Asian patients; this may be attributable to careful patient selection in case of ALF, though improvement of patient management may have contributed.

Efficient management of diabetic ketoacidosis (DKA) improves outcomes and reduces length of stay. While clinical audit improves the management of DKA, significant and sustained improvement is often difficult to achieve. We aimed to improve the management of DKA in our trust through the implementation of quality improvement methodology. Five specific targets (primary drivers: fluid prescription, fixed rate intravenous insulin infusion, glucose measurement, ketone measurement and specialist referral) were selected following a baseline audit. Interventions (secondary drivers) were developed to improve these targets and included monthly feedback to departments of emergency medicine, acute medicine, and diabetes. Following our intervention, the mean average duration of DKA reduced from 22.0 hours to 10.2 hours. We demonstrate that regular audit cycles with interventions introduced through the plan-do-study-act model is an effective way to improve the management of DKA.