Missed opportunities to use rapid influenza testing and severity assessment to avoid hospital admission: A cohort study from an East London District General Hospital.

Annual outbreaks of seasonal influenza cause a substantial health burden. The aim of this study was to compare patient demographic/clinical data in two influenza patient groups presenting to hospital; those requiring O2 or critical care admission and those requiring less intensive treatment. The study was conducted from 1 December 2017 until 1 April 2019 at a district general hospital in East London. Patient demographic and clinical information was collected for all patients who had tested influenza positive by near-patient testing. χ2 test was used for categorical variables to see if there were significant differences for those admitted and the Wilcoxon rank-sum test to compare the length of inpatient stay. Of 127 patients, 56 (44.1%) required oxygen or critical care. There were significant increases in National Early Warning Score (NEWS) observations (P %3C .001), Charlson comorbidity index (P = .049), length of inpatient stay (P %3C .001), and a strong association with increasing age (P = .066) when the more intensive treatment group was compared with the less intensive treatment group. A total of 13 (18.3%) of 71 patients not requiring oxygen or critical care were not admitted to the hospital. Following rapid influenza testing, NEWS scores, comorbidities, and age should be incorporated into a decision tool in Accident and Emergency to aid hospital admission or discharge decisions.

The difference in mortality between adult patients with laboratory documented influenza A and B, a single centre retrospective observational study.

BACKGROUND: Seasonal influenza is an annual occurrence that leads to large community outbreaks and increased hospitalization. A number of studies have suggested that influenza A (FLUAV) is associated with increased rates of hospitalization and mortality compared with influenza B (FLUBV). This study compared demographic and clinical variables in patients diagnosed with FLUAV or FLUBV during the 2017-2018 UK Influenza season. METHODS: Patient demographic and clinical information were obtained by accessing medical records of patients testing FLUAV or FLUBV positive using the Cepheid GXP. We used the χ2 test to compare variables in patients with laboratory-confirmed FLUAV and FLUBV. RESULTS: One hundred and twenty-seven adult patients had confirmed Influenza, 71 (55.9%) had FLUAV, and 56 (44.1%) FLUBV. There was no significant difference between severity at presentation, admission to HDU/ITU or median length of stay. The overall mortality was 6 (4.5%) and 9 (7.1%) at 7 and 30 days, respectively. There was a statistically significant difference in 7-day mortality between patients with FLUAV and FLUBV, 1 (1.4%) versus 5 (8.9%), respectively, p = .047) although this became nonsignificant at 30 days. CONCLUSIONS: With the exception of mortality, we did not observe significant differences between patients with FLUAV and FLUBV. Seven-day mortality in patients with FLUBV was significantly higher with FLUAV, although this was was not apparent at 30 days.

Impact on survival of modelling increased surgical resection rates in patients with non-small-cell lung cancer and cardiovascular comorbidities: a VICORI study.

BACKGROUND: The impact of cardiovascular disease (CVD) comorbidity on resection rates and survival for patients with early-stage non-small-cell lung cancer (NSCLC) is unclear. We explored if CVD comorbidity explained surgical resection rate variation and the impact on survival if resection rates increased. METHODS: Cancer registry data consisted of English patients diagnosed with NSCLC from 2012 to 2016. Linked hospital records identified CVD comorbidities. We investigated resection rate variation by geographical region using funnel plots; resection and death rates using time-to-event analysis. We modelled an increased propensity for resection in regions with the lowest resection rates and estimated survival change. RESULTS: Among 57,373 patients with Stage 1-3A NSCLC, resection rates varied considerably between regions. Patients with CVD comorbidity had lower resection rates and higher mortality rates. CVD comorbidity explained only 1.9% of the variation in resection rates. For every 100 CVD comorbid patients, increasing resection in regions with the lowest rates from 24 to 44% would result in 16 more patients resected and alive after 1 year and two fewer deaths overall. CONCLUSIONS: Variation in regional resection rate is not explained by CVD comorbidities. Increasing resection in patients with CVD comorbidity to the levels of the highest resecting region would increase 1-year survival.

Phenome-wide association analysis of LDL-cholesterol lowering genetic variants in PCSK9.

BACKGROUND: We characterised the phenotypic consequence of genetic variation at the PCSK9 locus and compared findings with recent trials of pharmacological inhibitors of PCSK9. METHODS: Published and individual participant level data (300,000+ participants) were combined to construct a weighted PCSK9 gene-centric score (GS). Seventeen randomized placebo controlled PCSK9 inhibitor trials were included, providing data on 79,578 participants. Results were scaled to a one mmol/L lower LDL-C concentration. RESULTS: The PCSK9 GS (comprising 4 SNPs) associations with plasma lipid and apolipoprotein levels were consistent in direction with treatment effects. The GS odds ratio (OR) for myocardial infarction (MI) was 0.53 (95% CI 0.42; 0.68), compared to a PCSK9 inhibitor effect of 0.90 (95% CI 0.86; 0.93). For ischemic stroke ORs were 0.84 (95% CI 0.57; 1.22) for the GS, compared to 0.85 (95% CI 0.78; 0.93) in the drug trials. ORs with type 2 diabetes mellitus (T2DM) were 1.29 (95% CI 1.11; 1.50) for the GS, as compared to 1.00 (95% CI 0.96; 1.04) for incident T2DM in PCSK9 inhibitor trials. No genetic associations were observed for cancer, heart failure, atrial fibrillation, chronic obstructive pulmonary disease, or Alzheimer's disease - outcomes for which large-scale trial data were unavailable. CONCLUSIONS: Genetic variation at the PCSK9 locus recapitulates the effects of therapeutic inhibition of PCSK9 on major blood lipid fractions and MI. While indicating an increased risk of T2DM, no other possible safety concerns were shown; although precision was moderate.

Does pattern mixture modelling reduce bias due to informative attrition compared to fitting a mixed effects model to the available cases or data imputed using multiple imputation?: a simulation study.

BACKGROUND: Informative attrition occurs when the reason participants drop out from a study is associated with the study outcome. Analysing data with informative attrition can bias longitudinal study inferences. Approaches exist to reduce bias when analysing longitudinal data with monotone missingness (once participants drop out they do not return). However, findings may differ when using these approaches to analyse longitudinal data with non-monotone missingness. METHODS: Different approaches to reduce bias due to informative attrition in non-monotone longitudinal data were compared. To achieve this aim, we simulated data from a Whitehall II cohort epidemiological study, which used the slope coefficients from a linear mixed effects model to investigate the association between smoking status at baseline and subsequent decline in cognition scores. Participants with lower cognitive scores were thought to be more likely to drop out. By using a simulation study, a range of scenarios using distributions of variables which exist in real data were compared. Informative attrition that would introduce a known bias to the simulated data was specified and the estimates from a mixed effects model with random intercept and slopes when fitted to: available cases; data imputed using multiple imputation (MI); imputed data adjusted using pattern mixture modelling (PMM) were compared. The two-fold fully conditional specification MI approach, previously validated for non-monotone longitudinal data under ignorable missing data assumption, was used. However, MI may not reduce bias because informative attrition is non-ignorable missing. Therefore, PMM was applied to reduce the bias, usually unknown, by adjusting the values imputed with MI by a fixed value equal to the introduced bias. RESULTS: With highly correlated repeated outcome measures, the slope coefficients from a mixed effects model were found to have least bias when fitted to available cases. However, for moderately correlated outcome measurements, the slope coefficients from fitting a mixed effects model to data adjusted using PMM were least biased but still underestimated the true coefficients. CONCLUSIONS: PMM may potentially reduce bias in studies analysing longitudinal data with suspected informative attrition and moderately correlated repeated outcome measurements. Including additional auxiliary variables in the imputation model may also reduce any remaining bias.

The utility of a blood culture database to identify patients suitable for outpatient parenteral antibiotic treatment.

BACKGROUND: The clinical and cost-effectiveness of outpatient parenteral antimicrobial therapy (OPAT) services are well described. We used a blood culture database as a novel approach to case finding and determined its utility in identifying inpatients suitable for OPAT. METHODS: From December 2012 to November 2013, consecutive adult inpatients with bacteraemia, and those recruited to OPAT, were prospectively studied. Univariate and multivariate logistic regression analysis were used to investigate the association between bacteraemic patient characteristics and OPAT recruitment. RESULTS: There were 470 bacteraemic and 134 OPAT patients. The blood culture database identified 22 (16.4%; CI 10.5 to 23.6) additional patients suitable for OPAT, 4.7% (95% CI 3.0% to 7.0%) of the total bacteraemic cohort. 20 (90.9%) of these patients had community-acquired bacteraemia. Bacteraemic patients with urinary tract infections (UTIs), 11/157 (7.0%; 95% CI 3.5% to 12.2%) were most commonly recruited to OPAT and Escherichia coli was the most common blood culture isolate. In the E. coli bacteraemic subgroup, extended-spectrum ß-lactamase (ESBL) producers were significantly higher in the OPAT group, compared with the non-OPAT group, 9/11 (81.8%) vs 17/192 (8.9%), p<0.001. Among OPAT patients, there were no deaths within 30 days and no significant difference in relapse rates between bacteraemic and non-bacteraemic patients, 1/22 (4.6%) vs 5/112 (4.5%). In logistic regression analysis, there were no patient characteristics in the bacteraemic cohort that predicted recruitment to OPAT. In a subgroup analysis of patients with Gram-negative bacteraemia, ESBL production was strongly associated with OPAT recruitment, OR 5.85 (95% CI 1.94 to 17.58), p=0.002. CONCLUSIONS: A blood culture database proved a useful adjuvant to a clinical referral system, particularly for patients with community onset, multidrug resistant UTIs caused by ESBL producing E. coli. All bacteraemic patients recruited to OPAT received treatment safely and had good clinical outcomes.

The characteristics and outcome of bacteraemia in renal transplant recipients and non-transplant renal patients.

BACKGROUND: There is lack of outcome data for bacteraemic patients on specialist renal units. We described demographic, clinical, microbiological data and outcomes for bacteraemic adult renal transplant and non-transplant patients at a London Teaching Hospital. We also assessed the appropriateness of empirical antibiotic policy. METHODS: From December 2012 to November 2013, demographic, clinical and microbiological data were collected on consecutive patients with bacteraemia on a specialist UK renal unit. Empirical anti-microbial policy, based upon sites of infection, was piperacillin/tazobactam and amikacin, or meropenem for graft pyelonephritis, and vancomycin and gentamicin for suspected central venous catheter (CVC) associated infection. RESULTS: 113 bacteraemic episodes occurred in 83 patients. One patient had two bacteraemic episodes, one on haemodialysis and another after transplantation so appear in both groups. In the non-transplant group, 30-day mortality was 4/59 (6.8 %), more than the renal transplant group, 0/25 (0 %). While graft pyelonephritis was the predominant cause of bacteraemic episodes in renal transplant patients, 25/36 (69.4 %), there were a variety of other causes in the non-transplant group including uncomplicated line associated bacteraemia, 36/77 (46.8 %), complicated line associated bacteraemia, 11/77 (14.3 %) and bacteraemia unrelated to vascular access sites 19/77 (24.7 %). Overall, commonest isolates were Methicillin-sensitive Staphylococcus aureus 20/77 (26.3 %), and Escherichia coli 28/113 (24.8 %). There were no Methicillin-resistant Staphylococcus aureus isolates and, among Enterobacteriaceae, 15/57 (26.3 %) were extended spectrum beta-lactamase producers. CONCLUSIONS: Death only occurred in the non-transplant renal group. Empirical antibiotic treatment with either piperacillin/tazobactam and amikacin, or meropenem was appropriate for renal transplant recipients as most bacteraemic episodes were secondary to graft pyelonephritis. Vancomycin and gentamicin was appropriate empirical antibiotic treatment for non-transplant patients with CVC associated infections, but not optimal for other sites of infection.

Evaluation of two-fold fully conditional specification multiple imputation for longitudinal electronic health record data.

Most implementations of multiple imputation (MI) of missing data are designed for simple rectangular data structures ignoring temporal ordering of data. Therefore, when applying MI to longitudinal data with intermittent patterns of missing data, some alternative strategies must be considered. One approach is to divide data into time blocks and implement MI independently at each block. An alternative approach is to include all time blocks in the same MI model. With increasing numbers of time blocks, this approach is likely to break down because of co-linearity and over-fitting. The new two-fold fully conditional specification (FCS) MI algorithm addresses these issues, by only conditioning on measurements, which are local in time. We describe and report the results of a novel simulation study to critically evaluate the two-fold FCS algorithm and its suitability for imputation of longitudinal electronic health records. After generating a full data set, approximately 70% of selected continuous and categorical variables were made missing completely at random in each of ten time blocks. Subsequently, we applied a simple time-to-event model. We compared efficiency of estimated coefficients from a complete records analysis, MI of data in the baseline time block and the two-fold FCS algorithm. The results show that the two-fold FCS algorithm maximises the use of data available, with the gain relative to baseline MI depending on the strength of correlations within and between variables. Using this approach also increases plausibility of the missing at random assumption by using repeated measures over time of variables whose baseline values may be missing.

Application of multiple imputation using the two-fold fully conditional specification algorithm in longitudinal clinical data.

Electronic health records of longitudinal clinical data are a valuable resource for health care research. One obstacle of using databases of health records in epidemiological analyses is that general practitioners mainly record data if they are clinically relevant. We can use existing methods to handle missing data, such as multiple imputation (mi), if we treat the unavailability of measurements as a missing-data problem. Most software implementations of MI do not take account of the longitudinal and dynamic structure of the data and are difficult to implement in large databases with millions of individuals and long follow-up. Nevalainen, Kenward, and Virtanen (2009, Statistics in Medicine 28: 3657-3669) proposed the two-fold fully conditional specification algorithm to impute missing data in longitudinal data. It imputes missing values at a given time point, conditional on information at the same time point and immediately adjacent time points. In this article, we describe a new command, twofold, that implements the two-fold fully conditional specification algorithm. It is extended to accommodate MI of longitudinal clinical records in large databases.

A pilot study to investigate the clinically predictive values of copy number variations detected by next-generation sequencing of cell-free deoxyribonucleic acid in spent culture media.

OBJECTIVE: To investigate the positive predictive value and false positive risk of copy number variations (CNV's) detected in cell free deoxyribonucleic acid (DNA) from spent culture media for nonviable or aneuploid embryos. DESIGN: Diagnostic/prognostic accuracy study. PATIENT(S): Patients aged 35 and younger with an indication for IVF-ICSI and elective single frozen embryo transfer at a single, private IVF center. INTERVENTION: Embryo selection was performed according to the conventional grading, blinded to noninvasive preimplantation genetic testing for aneuploidy (niPGT-A) results. After clinical outcomes were established, spent culture media samples were analyzed. MAIN OUTCOME MEASURES: Prognostic accuracy of CNVs according to niPGT-A results to predict nonviability or clinical aneuploidy. RESULTS: One hundred twenty patients completed the study. Interpretations of next-generation sequencing (NGS) profiles were as follows: 7.5% (n = 9) failed quality control; 62.5% (n = 75) no CNVs detected; and 30% (n = 36) abnormal copy number detected. Stratification of abnormal NGS profiles was as follows: 15% (n = 18) whole chromosome and 15% (n = 18) uncertain reproductive potential. An intermediate CNV was evident in 27.8% (n = 5) of the whole chromosome abnormalities. The negative predictive value for samples with no detected abnormality was 57.3% (43/75). Whole chromosome abnormality was associated with a positive predictive value of 94.4% (17/18), lower sustained implantation rate (5.6%, 1/18), and higher relative risk (RR) for nonviability compared with no detected abnormalities (RR 2.21, 95% CI: 1.66-2.94). No other CNVs were associated with significant differences in the sustained implantation or RRs for nonviability. Unequal sex chromosome proportions suggested that maternal contamination was not uncommon. A secondary descriptive analysis of 705 supernumerary embryos revealed proportions of NGS profile interpretations similar to the transferred cohort. Significant median absolute pairwise differences between certain subcategories of CNV abnormalities were apparent. CONCLUSION: Whole chromosome abnormalities were associated with a high positive predictive value and significant RR for nonviability. Embryos associated with other CNVs had sustained implantation rates similar to those with no abnormalities detected. Further studies are required to validate the clinical applicability of niPGT-A. CLINICAL TRIAL REGISTRATION NUMBER: clinicaltrials.gov (NCT04732013).

Outcomes in UK patients with hospital-acquired bacteraemia and the risk of catheter-associated urinary tract infections.

PURPOSE: There is lack of contemporary outcome data on patients with hospital-acquired infections that cause bacteraemia. We determined the risk factors for 7-day mortality and investigated the hypothesis that, compared with central venous catheter (CVC)-associated bacteraemic infections, catheter-associated bacteraemic urinary tract infections (UTIs) were significantly associated with 7-day mortality. METHODS: From October 2007 to September 2008, demographical, clinical and microbiological data were collected on patients with hospital-acquired bacteraemia. Patients were followed until death, hospital discharge or recovery from infection. Risk factors for 7-day mortality were determined and multivariate logistic regression was used to define the association between catheter-associated bacteraemic UTIs and likelihood of death. RESULTS: 559 bacteraemic episodes occurred in 437 patients. Overall, there were 90 deaths (20.6%) at 7 days and 153 deaths (35.0%) at 30 days. Among patients with catheter-associated bacteraemic UTIs, 7-day and 30-day mortalities associated with each bacteraemic episode were 25/83 (30.1%) and 33/83 (39.8%), respectively. Within this subgroup, the commonest isolates were Escherichia coli, 36 (43.4%), Proteus mirabilis, 11 (13.3%) and Pseudomonas aeruginosa, 9 (10.8%). There were 22 (26.5%) multiple drug-resistant isolates and, of the E coli infections, 6 (16.7%) were extended spectrum ß-lactamase producers. In univariate analysis, the variables found to have the strongest association with 7-day mortality were age, Pitt score, Charlson comorbidity index (CCI), medical speciality and site of infection. Compared with CVC-associated bacteraemic infections, there was a significant association between catheter-associated bacteraemic UTIs and 7-day mortality (OR 4.16, 95% CI 1.86 to 9.33). After adjustment for age and CCI, this association remained significant (OR 2.90, 95% CI 1.19 to 7.07). CONCLUSIONS: Compared with CVC-associated bacteraemic infections, catheter-associated bacteraemic UTIs were significantly associated with 7-day mortality. Efforts to reduce these infections should be prioritised.

Acute heart failure presentation, management, and outcomes in cancer patients: a national longitudinal study.

AIMS: Currently, little evidence exists on survival and quality of care in cancer patients presenting with acute heart failure (HF). The aim of the study is to investigate the presentation and outcomes of hospital admission with acute HF in a national cohort of patients with prior cancer. METHODS AND RESULTS: This retrospective, population-based cohort study identified 221 953 patients admitted to a hospital in England for HF during 2012-2018 (12 867 with a breast, prostate, colorectal, or lung cancer diagnosis in the previous 10 years). We examined the impact of cancer on (i) HF presentation and in-hospital mortality, (ii) place of care, (iii) HF medication prescribing, and (iv) post-discharge survival, using propensity score weighting and model-based adjustment. Heart failure presentation was similar between cancer and non-cancer patients. A lower percentage of patients with prior cancer were cared for in a cardiology ward [-2.4% age point difference (ppd) (95% CI -3.3, -1.6)] or were prescribed angiotensin-converting enzyme inhibitors or angiotensin receptor antagonists (ACEi/ARB) for heart failure with reduced ejection fraction [-2.1 ppd (-3.3, -0.9)] than non-cancer patients. Survival after HF discharge was poor with median survival of 1.6 years in prior cancer and 2.6 years in non-cancer patients. Mortality in prior cancer patients was driven primarily by non-cancer causes (68% of post-discharge deaths). CONCLUSION: Survival in prior cancer patients presenting with acute HF was poor, with a significant proportion due to non-cancer causes of death. Despite this, cardiologists were less likely to manage cancer patients with HF. Cancer patients who develop HF were less likely to be prescribed guideline-based HF medications compared with non-cancer patients. This was particularly driven by patients with a poorer cancer prognosis.

Prevalence of Cardiovascular Disease in Patients With Potentially Curable Malignancies: A National Registry Dataset Analysis.

Background: Although a common challenge for patients and clinicians, there is little population-level evidence on the prevalence of cardiovascular disease (CVD) in individuals diagnosed with potentially curable cancer. Objectives: We investigated CVD rates in patients with common potentially curable malignancies and evaluated the associations between patient and disease characteristics and CVD prevalence. Methods: The study included cancer registry patients diagnosed in England with stage I to III breast cancer, stage I to III colon or rectal cancer, stage I to III prostate cancer, stage I to IIIA non-small-cell lung cancer, stage I to IV diffuse large B-cell lymphoma, and stage I to IV Hodgkin lymphoma from 2013 to 2018. Linked hospital records and national CVD databases were used to identify CVD. The rates of CVD were investigated according to tumor type, and associations between patient and disease characteristics and CVD prevalence were determined. Results: Among the 634,240 patients included, 102,834 (16.2%) had prior CVD. Men, older patients, and those living in deprived areas had higher CVD rates. Prevalence was highest for non-small-cell lung cancer (36.1%) and lowest for breast cancer (7.7%). After adjustment for age, sex, the income domain of the Index of Multiple Deprivation, and Charlson comorbidity index, CVD remained higher in other tumor types compared to breast cancer patients. Conclusions: There is a significant overlap between cancer and CVD burden. It is essential to consider CVD when evaluating national and international treatment patterns and cancer outcomes.

Case-ascertainment of acute myocardial infarction hospitalizations in cancer patients: a cohort study using English linked electronic health data.

AIMS: To assess the recording and accuracy of acute myocardial infarction (AMI) hospital admissions between two electronic health record databases within an English cancer population over time and understand the factors that affect case-ascertainment. METHODS AND RESULTS: We identified 112 502 hospital admissions for AMI in England 2010-2017 from the Myocardial Ischaemia National Audit Project (MINAP) disease registry and hospital episode statistics (HES) for 95 509 patients with a previous cancer diagnosis up to 15 years prior to admission. Cancer diagnoses were identified from the National Cancer Registration Dataset (NCRD). We calculated the percentage of AMI admissions captured by each source and examined patient characteristics associated with source of ascertainment. Survival analysis assessed whether differences in survival between case-ascertainment sources could be explained by patient characteristics. A total of 57 265 (50.9%) AMI admissions in patients with a prior diagnosis of cancer were captured in both MINAP and HES. Patients captured in both sources were younger, more likely to have ST-segment elevation myocardial infarction and had better prognosis, with lower mortality rates up to 9 years after AMI admission compared with patients captured in only one source. The percentage of admissions captured in both data sources improved over time. Cancer characteristics (site, stage, and grade) had little effect on how AMI was captured. CONCLUSION: MINAP and HES define different populations of patients with AMI. However, cancer characteristics do not substantially impact on case-ascertainment. These findings support a strategy of using multiple linked data sources for observational cardio-oncological research into AMI.

Admission factors associated with hospital mortality in patients with haematological malignancy admitted to UK adult, general critical care units: a secondary analysis of the ICNARC Case Mix Programme Database.

INTRODUCTION: Patients with haematological malignancy admitted to intensive care have a high mortality. Adverse prognostic factors include the number of organ failures, invasive mechanical ventilation and previous bone marrow transplantation. Severity-of-illness scores may underestimate the mortality of critically ill patients with haematological malignancy. This study investigates the relationship between admission characteristics and outcome in patients with haematological malignancies admitted to intensive care units (ICUs) in England, Wales and Northern Ireland, and assesses the performance of three severity-of-illness scores in this population. METHODS: A secondary analysis of the Intensive Care National Audit and Research Centre (ICNARC) Case Mix Programme Database was conducted on admissions to 178 adult, general ICUs in England, Wales and Northern Ireland between 1995 and 2007. Multivariate logistic regression analysis was used to identify factors associated with hospital mortality. The Acute Physiology and Chronic Health Evaluation (APACHE) II score, Simplified Acute Physiology Score (SAPS) II and ICNARC score were evaluated for discrimination (the ability to distinguish survivors from nonsurvivors); and the APACHE II, SAPS II and ICNARC mortality probabilities were evaluated for calibration (the accuracy of the estimated probability of survival). RESULTS: There were 7,689 eligible admissions. ICU mortality was 43.1% (3,312 deaths) and acute hospital mortality was 59.2% (4,239 deaths). ICU and hospital mortality increased with the number of organ failures on admission. Admission factors associated with an increased risk of death were bone marrow transplant, Hodgkin's lymphoma, severe sepsis, age, length of hospital stay prior to intensive care admission, tachycardia, low systolic blood pressure, tachypnoea, low Glasgow Coma Score, sedation, PaO2:FiO2, acidaemia, alkalaemia, oliguria, hyponatraemia, hypernatraemia, low haematocrit, and uraemia. The ICNARC model had the best discrimination of the three scores analysed, as assessed by the area under the receiver operating characteristic curve of 0.78, but all scores were poorly calibrated. APACHE II had the highest accuracy at predicting hospital mortality, with a standardised mortality ratio of 1.01. SAPS II and the ICNARC score both underestimated hospital mortality. CONCLUSIONS: Increased hospital mortality is associated with the length of hospital stay prior to ICU admission and with severe sepsis, suggesting that, if appropriate, such patients should be treated aggressively with early ICU admission. A low haematocrit was associated with higher mortality and this relationship requires further investigation. The severity-of-illness scores assessed in this study had reasonable discriminative power, but none showed good calibration.

Outcomes following oesophagectomy in patients with oesophageal cancer: a secondary analysis of the ICNARC Case Mix Programme Database.

INTRODUCTION: This report describes the case mix and outcomes of patients with oesophageal cancer admitted to adult critical care units following elective oesophageal surgery in England, Wales and Northern Ireland. METHODS: Admissions to critical care following elective oesophageal surgery for malignancy were identified using data from the Intensive Care National Audit and Research Centre (ICNARC) Case Mix Programme Database. Information on admissions between December 1995 and September 2007 were extracted and the association between in-hospital mortality and patient characteristics on admission to critical care was assessed using multiple logistic regression analysis. The performance of three prognostic models (Simplified Acute Physiology Score (SAPS) II, Acute Physiology and Chronic Health Evaluation (APACHE) II and the ICNARC physiology score) was also evaluated. RESULTS: Between 1995 and 2007, there were 7227 admissions to 181 critical care units following oesophageal surgery for malignancy. Overall mortality in critical care was 4.4% and in-hospital mortality was 11%, although both declined steadily over time. Eight hundred and seventy-three (12.2%) patients were readmitted to critical care, most commonly for respiratory complications (49%) and surgical complications (25%). Readmitted patients had a critical care unit mortality of 24.7% and in-hospital mortality of 33.9%. Overall in-hospital mortality was associated with patient age, and various physiological measurements on admission to critical care (partial pressure of arterial oxygen (PaO2):fraction of inspired oxygen (FiO2) ratio, lowest arterial pH, mechanical ventilation, serum albumin, urea and creatinine). The three prognostic models evaluated performed poorly in measures of discrimination, calibration and goodness of fit. CONCLUSIONS: Surgery for oesophageal malignancy continues to be associated with significant morbidity and mortality. Age and organ dysfunction in the early postoperative period are associated with an increased risk of death. Postoperative serum albumin is confirmed as an additional prognostic factor. More work is required to determine how this knowledge may improve clinical management.

Is Strongyloides seropositivity associated with diabetes mellitus? A retrospective case-control study in an East London NHS Trust.

BACKGROUND: The association between diabetes and Strongyloides stercoralis remains controversial. We conducted a case-control study examining the association between diabetes and Strongyloides seropositivity in a large UK centre. METHODS: Between January 2013 and October 2016, cases and controls were identified by positive and negative Strongyloides serology, respectively. Demographic, clinical and microbiological data were retrospectively collected. Multivariate logistic regression analysis was performed. RESULTS: Over the study period, 532 samples were serologically tested for Strongyloides. After exclusion of duplicates and cases with missing data, 100 (22.3%; 95% CI 18.5-26.4%) out of 449 tested positive. Of seropositive cases, the mean age was 57 years (SD 16), 71 (71%) were male, 94 (94%) were migrants and 92 (92%) had eosinophilia.Univariate logistic regression analysis demonstrated a significant association between Strongyloides seropositivity and age (OR 1.04, 95% CI 1.02-1.05), male sex (OR 2.22, 95% CI 1.37-3.59), migration (OR 5.36, 95% CI 2.27-12.67), eosinophilia (OR 4.36, 95% CI 2.04-9.33) and diabetes (OR 3.52, 95% CI 2.19-5.66). In multivariate analysis, there remained a significant association between diabetes and Strongyloides seropositivity (OR 1.81, 95% CI 1.04-3.16). CONCLUSIONS: We demonstrated a high rate of Strongyloides seropositivity in our East London cohort and a significant association with diabetes.

The construction and the initial validation of the Cognitive Bias Scale for the Personality Assessment Inventory.

Objective: This study describes the derivation and initial validation evidence of a novel Personality Assessment Inventory (PAI) scale designed to be sensitive to cognitive response bias, as defined by poor performance on performance validity tests (PVTs), in the context of neuropsychological assessment. The Cognitive Bias Scale (CBS) is a ten-item scale that was designed to discriminate between neuropsychological patients who passed or failed PVTs. Method: In a sample of 306 consecutive mixed neuropsychological outpatients, the CBS was derived by initially selecting items that significantly discriminated participants who passed and failed two or more PVTs, with further item refinement utilizing Item Response Theory methods. Results: Initial validation evidence suggests the CBS outperforms existing PAI symptom validity tests in predicting failure on two or more PVTs. The CBS showed good ability to discriminate between valid and invalid performance validity (Cohen's d = -0.96), with good classification accuracy (area under the curve = 0.72). Conclusions: Study results suggest the CBS may be useful in detecting cognitive response bias in a mixed neuropsychological outpatient sample; however, cross-validation will be necessary to further establish its utility.

Health indicator recording in UK primary care electronic health records: key implications for handling missing data.

BACKGROUND: Clinical databases are increasingly used for health research; many of them capture information on common health indicators including height, weight, blood pressure, cholesterol level, smoking status, and alcohol consumption. However, these are often not recorded on a regular basis; missing data are ubiquitous. We described the recording of health indicators in UK primary care and evaluated key implications for handling missing data. METHODS: We examined the recording of health indicators in The Health Improvement Network (THIN) UK primary care database over time, by demographic variables (age and sex) and chronic diseases (diabetes, myocardial infarction, and stroke). Using weight as an example, we fitted linear and logistic regression models to examine the associations of weight measurements and the probability of having weight recorded with individuals' demographic characteristics and chronic diseases. RESULTS: In total, 6,345,851 individuals aged 18-99 years contributed data to THIN between 2000 and 2015. Women aged 18-65 years were more likely than men of the same age to have health indicators recorded; this gap narrowed after age 65. About 60-80% of individuals had their height, weight, blood pressure, smoking status, and alcohol consumption recorded during the first year of registration. In the years following registration, these proportions fell to 10%-40%. Individuals with chronic diseases were more likely to have health indicators recorded, particularly after the introduction of a General Practitioner incentive scheme. Individuals' demographic characteristics and chronic diseases were associated with both observed weight measurements and missingness in weight. CONCLUSION: Missing data in common health indicators will affect statistical analysis in health research studies. A single analysis of primary care data using the available information alone may be misleading. Multiple imputation of missing values accounting for demographic characteristics and disease status is recommended but should be considered and implemented carefully. Sensitivity analysis exploring alternative assumptions for missing data should also be evaluated.

Association of the PHACTR1/EDN1 Genetic Locus With Spontaneous Coronary Artery Dissection.

BACKGROUND: Spontaneous coronary artery dissection (SCAD) is an increasingly recognized cause of acute coronary syndromes (ACS) afflicting predominantly younger to middle-aged women. Observational studies have reported a high prevalence of extracoronary vascular anomalies, especially fibromuscular dysplasia (FMD) and a low prevalence of coincidental cases of atherosclerosis. PHACTR1/EDN1 is a genetic risk locus for several vascular diseases, including FMD and coronary artery disease, with the putative causal noncoding variant at the rs9349379 locus acting as a potential enhancer for the endothelin-1 (EDN1) gene. OBJECTIVES: This study sought to test the association between the rs9349379 genotype and SCAD. METHODS: Results from case control studies from France, United Kingdom, United States, and Australia were analyzed to test the association with SCAD risk, including age at first event, pregnancy-associated SCAD (P-SCAD), and recurrent SCAD. RESULTS: The previously reported risk allele for FMD (rs9349379-A) was associated with a higher risk of SCAD in all studies. In a meta-analysis of 1,055 SCAD patients and 7,190 controls, the odds ratio (OR) was 1.67 (95% confidence interval [CI]: 1.50 to 1.86) per copy of rs9349379-A. In a subset of 491 SCAD patients, the OR estimate was found to be higher for the association with SCAD in patients without FMD (OR: 1.89; 95% CI: 1.53 to 2.33) than in SCAD cases with FMD (OR: 1.60; 95% CI: 1.28 to 1.99). There was no effect of genotype on age at first event, P-SCAD, or recurrence. CONCLUSIONS: The first genetic risk factor for SCAD was identified in the largest study conducted to date for this condition. This genetic link may contribute to the clinical overlap between SCAD and FMD.