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.

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.

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.

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.

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.

Post hoc insights from PAC-Man--the U.K. pulmonary artery catheter trial.

OBJECTIVES: To provide descriptive information on patients considered for management with a pulmonary artery catheter (PAC) in U.K. intensive care units and to generate hypotheses to guide future research by examining subsets of patients included in the PAC-Man Study. DESIGN: Randomized controlled trial. SETTING: U.K. general intensive care units. PATIENTS: Adult critically ill patients deemed to require management with a PAC by the treating clinician. INTERVENTIONS: Management with a PAC. MEASUREMENTS AND MAIN RESULTS: A Cox proportional hazards model was used to estimate interactions between treatment effect and time to randomization, age, surgical status, Sequential Organ Failure Score (SOFA) at randomization, organs supported at randomization, and use of flow measurement devices. Type of hospital and size of unit were tested for an interaction with the treatment effect using multilevel logistic regression modeling. There was no effect (or trend) on hospital survival related to the timing of randomization in relation to intensive care unit admission, type of organ support or SOFA score at randomization, age, type of hospital, or size of intensive care unit. No overall difference in acute hospital outcome was seen between use of a PAC and no flow measurement (p = .748) or between use of an alternative flow measurement device and no flow measurement (p = .395). CONCLUSIONS: Post hoc analyses of the PAC-Man Study data set revealed no benefit associated with being managed with a PAC in critically ill patients. However, such analyses are limited, and adequately powered clinical trials are needed of specific population subsets receiving targeted therapies delivered early in the patient's critical illness to optimize the likelihood of reversing or preventing further organ dysfunction. Furthermore, the utility of other flow measurement devices must be investigated as these have already become integrated into critical care management without adequate evaluation.

Drotrecogin alfa (activated): real-life use and outcomes for the UK.

INTRODUCTION: In March 2001, the results of the Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) study were published, which indicated a 6.1% absolute reduction in 28-day mortality. Drotrecogin alfa (activated; DrotAA) was subsequently approved for use in patients with severe sepsis. METHODS: In December 2002, critical care units in England, Wales and Northern Ireland were invited to participate in an audit of DrotAA. Data for each infusion of DrotAA were linked to case mix and outcome data from a national audit. Use of DrotAA was described and a nonrandomized comparison of effectiveness was conducted. RESULTS: 1,292 infusions of DrotAA were recorded in 112 units; 61% commenced during the first 24 hours in the unit. The majority (77%) of patients had three or more organs failing; lung (42%) and abdomen (40%) were the most common primary sites of infection. Crude hospital mortality was high (45%); at 28 days, only 18% had left acute hospital and 19% were still in the unit. For 30%, the full 96-hour infusion was not completed; 24% of infusions were interrupted; 8.1% experienced one or more serious adverse events, of which 77% were serious bleeding events. Of eight relative risks estimated from individually-matched (0.75 to 0.85) and propensity-matched (0.82 to 0.90) controls, seven were consistent with the results of PROWESS. Restricting the analysis to patients receiving DrotAA during the first 24 hours resulted in larger treatment effects (relative risks 0.62 to 0.81). For all matches, similar patterns were seen across subgroups. No effect of DrotAA was seen for two organs failing or lower severity scores, compared with a significant mortality reduction for three or more organs failing or higher severity scores. CONCLUSION: Use of DrotAA was approximately one in 16 for admissions meeting the definition for severe sepsis and with two or more organs failing. Patients receiving DrotAA were younger and more severely ill but were less likely to have serious conditions in their past medical history. Nonrandomized estimates for the effectiveness of DrotAA were consistent with the findings of PROWESS. DrotAA appeared not to be effective in patients with less severe disease.

Dermatological conditions in intensive care: a secondary analysis of the Intensive Care National Audit and Research Centre (ICNARC) Case Mix Programme database.

INTRODUCTION: Dermatology is usually thought of as an outpatient specialty with low mortality, however some skin conditions require intensive care. These conditions are relatively rare and hence are best studied using clinical databases or disease registries. We interrogated a large, high-quality clinical database from a national audit of adult intensive care units (ICUs), with the aim of identifying and characterising patients with dermatological conditions requiring admission to ICU. METHODS: Data were extracted for 476,224 admissions to 178 ICUs in England, Wales and Northern Ireland participating in the Case Mix Programme over the time period December 1995 to September 2006. We identified admissions with dermatological conditions from the primary and secondary reasons for admission to ICU. RESULTS: A total of 2,245 dermatological admissions were identified. Conditions included infectious conditions (e.g. cutaneous cellulitis, necrotising fasciitis), dermatological malignancies, and acute skin failure (e.g. toxic epidermal necrolysis, Stevens-Johnson syndrome and autoimmune blistering diseases). These represent 0.47% of all ICU admissions, or approximately 2.1 dermatological admissions per ICU per year. Overall mortality was 28.1% in the ICU and 40.0% in hospital. Length of stay in intensive care was longest for those with acute skin failure (median 4.7 days for ICU survivors and 5.1 days for ICU non-survivors). CONCLUSION: We have identified patients who not only require intensive care, but also dermatological care. Such patients have high mortality rates and long ICU stays within the spectrum of the UK ICU population, similar to other acute medical conditions. This highlights the importance of skin failure as a distinct entity comparable to other organ system failures.

Socioeconomic inequality in recovery from poor physical and mental health in mid-life and early old age: prospective Whitehall II cohort study.

BACKGROUND: Few studies have examined the influence of socioeconomic status on recovery from poor physical and mental health. METHODS: Prospective study with four consecutive periods of follow-up (1991-2011) of 7564 civil servants (2228 women) recruited while working in London. Health was measured by the Short-Form 36 questionnaire physical and mental component scores assessed at beginning and end of each of four rounds. Poor health was defined by a score in the lowest 20% of the age-sex-specific distribution. Recovery was defined as changing from a low score at the beginning to a normal score at the end of the round. The analysis took account of retirement status, health behaviours, body mass index and prevalent chronic disease. RESULTS: Of 24 001 person-observations in the age range 39-83, a total of 8105 identified poor physical or mental health. Lower grade of employment was strongly associated with slower recovery from poor physical health (OR 0.73 (95% CI 0.59 to 0.91); trend P=0.002) in age, sex and ethnicity-adjusted analyses. The association was halved after further adjustment for health behaviours, adiposity, systolic blood pressure (SBP) and serum cholesterol (OR 0.85 (0.68 to 1.07)). In contrast, slower recovery from poor mental health was associated robustly with low employment grade even after multiple adjustment (OR 0.74 (0.59 to 0.93); trend P=0.02). CONCLUSIONS: Socioeconomic inequalities in recovery from poor physical health were explained to a considerable extent by health behaviours, adiposity, SBP and serum cholesterol. These risk factors explained only part of the gradient in recovery for poor mental health.

A new measure of acute physiological derangement for patients with exacerbations of obstructive airways disease: the COPD and Asthma Physiology Score.

BACKGROUND: Decisions about how to treat patients with acute exacerbations of obstructive airways disease-chronic obstructive pulmonary disease (COPD), asthma or mixed diagnoses-often require an understanding of prognosis. This depends on the severity of the acute deterioration and the patient's functional reserve. There are currently no validated disease-specific scores that measure the severity of the acute exacerbation. OBJECTIVE: To develop an acute physiology score for exacerbations of obstructive airways disease. DESIGN: Secondary analysis of a high-quality clinical database, the Case Mix Programme Database. SETTING: One hundred and sixty-eight adult, general critical care units in England, Wales and Northern Ireland. RESULTS: A total of 8527 patients with obstructive airways disease were identified with a mean (SD) age of 65.9 (9.7) years and hospital mortality of 35.5%. The COPD and Asthma Physiology Score (CAPS) was developed using logistic regression. The CAPS included eight variables: heart rate, mean arterial blood pressure, pH, sodium, urea, creatinine, albumin and white blood cell count. The score had fair discrimination with an area under the receiver operating characteristic curve of 0.718. This performance was reproduced in a further validation dataset of 7957 patients. The discrimination of the CAPS in these validation data exceeded that of the acute physiology scores from APACHE II and III and the physiological components of SAPS II. CONCLUSION: The CAPS can be used to estimate the prognostic impact of physiological derangements accompanying an acute exacerbation of obstructive airways disease and has the potential for even greater predictive performance when combined with measures of a patient's functional reserve.

Midlife Risk Factors for Impaired Physical and Cognitive Functioning at Older Ages: A Cohort Study.

BACKGROUND: Previous studies examined midlife risk factors separately for old-age impaired physical and cognitive functioning. We determined the overlap of risk factors for both domains of functioning within the same setting. METHODS: Biological and behavioral risk factors at age 50 years and cognitive and physical functioning were assessed 18 (SD = 5) years later in the Whitehall II study (N = 6,316). Impaired physical functioning was defined as ≥1 limitation on the activities of daily living scale. Impaired cognitive functioning was defined as Mini-Mental State Examination score <27. Two statistical analyses were employed: minimally adjusted analysis (for age, sex, and ethnicity) and mutually adjusted analysis (including all risk factors). Missing data on risk factors were imputed. RESULTS: After confounder adjustment, impaired physical and cognitive functioning at older ages were predicted by hypertension (odds ratios [ORs] 1.80 95% confidence interval [CI] 1.39-2.33 and 1.57 95% CI 1.07-2.31, respectively), poor lung function (1.51 95% CI 1.28-1.78 and 1.31 95% CI 1.08-1.59), and physical inactivity, marginally in the case of cognitive function (1.50 95% CI 1.19-1.90 and 1.27 95% CI 0.99-1.62) at age 50 years. Impaired physical functioning but not cognitive functioning was additionally predicted by depression and higher body mass index (1.72 95% CI 1.46-2.03 and 1.29 95% CI 1.16-1.44, respectively). CONCLUSIONS: Several midlife risk factors are associated with impaired physical and cognitive functioning in old age, supporting a unified prevention policy. Analysis of 12 risk factors at age 50 suggests that strategies targeting physical inactivity, hypertension, and poor lung function will reduce impairments in both cognitive and physical functioning in old age.

The epidemiology of severe sepsis in England, Wales and Northern Ireland, 1996 to 2004: secondary analysis of a high quality clinical database, the ICNARC Case Mix Programme Database.

INTRODUCTION: To evaluate the impact of recent evidence-based treatments for severe sepsis in routine clinical care requires an understanding of the underlying epidemiology, particularly with regard to trends over time. We interrogated a high quality clinical database to examine trends in the incidence and mortality of severe sepsis over a nine-year period. METHODS: Admissions with severe sepsis occurring at any time within 24 hours of admission to critical care were identified to an established methodology using raw physiological data from the Intensive Care National Audit & Research Centre (ICNARC) Case Mix Programme Database, containing data from 343,860 admissions to 172 adult, general critical care units in England, Wales and Northern Ireland between December 1995 and January 2005. Generalised linear models were used to assess changes in the incidence, case mix, outcomes and activity of these admissions. RESULTS: In total, 92,672 admissions (27.0%) were identified as having severe sepsis in the first 24 hours following admission. The percentage of admissions with severe sepsis during the first 24 hours rose from 23.5% in 1996 to 28.7% in 2004. This represents an increase from an estimated 18,500 to 31,000 admissions to all 240 adult, general critical care units in England, Wales and Northern Ireland. Hospital mortality for admissions with severe sepsis decreased from 48.3% in 1996 to 44.7% in 2004, but the total number of deaths increased from an estimated 9,000 to 14,000. The treated incidence of severe sepsis per 100,000 population rose from 46 in 1996 to 66 in 2003, with the associated number of hospital deaths per 100,000 population rising from 23 to 30. CONCLUSION: The population incidence of critical care admission with severe sepsis during the first 24 hours and associated hospital deaths are increasing. These baseline data provide essential information to those wishing to evaluate the introduction of the Surviving Sepsis Campaign care bundles in UK hospitals.

Case mix, outcomes and comparison of risk prediction models for admissions to adult, general and specialist critical care units for head injury: a secondary analysis of the ICNARC Case Mix Programme Database.

INTRODUCTION: This report describes the case mix and outcome (mortality, intensive care unit (ICU) and hospital length of stay) for admissions to ICU for head injury and evaluates the predictive ability of five risk adjustment models. METHODS: A secondary analysis was conducted of data from the Intensive Care National Audit and Research Centre (ICNARC) Case Mix Programme, a high quality clinical database, of 374,594 admissions to 171 adult critical care units across England, Wales and Northern Ireland from 1995 to 2005. The discrimination and calibration of five risk prediction models, SAPS II, MPM II, APACHE II and III and the ICNARC model plus raw Glasgow Coma Score (GCS) were compared. RESULTS: There were 11,021 admissions following traumatic brain injury identified (3% of all database admissions). Mortality in ICU was 23.5% and in-hospital was 33.5%. Median ICU and hospital lengths of stay were 3.2 and 24 days, respectively, for survivors and 1.6 and 3 days, respectively, for non-survivors. The ICNARC model, SAPS II and MPM II discriminated best between survivors and non-survivors and were better calibrated than raw GCS, APACHE II and III in 5,393 patients eligible for all models. CONCLUSION: Traumatic brain injury requiring intensive care has a high mortality rate. Non-survivors have a short length of ICU and hospital stay. APACHE II and III have poorer calibration and discrimination than SAPS II, MPM II and the ICNARC model in traumatic brain injury; however, no model had perfect calibration.