Relative value of cystatin C and creatinine-based estimates of glomerular filtration rate in predicting long-term mortality after cardiac surgery: a cohort study.

OBJECTIVE: Renal dysfunction predicts an increased risk of both early and long-term mortality after cardiac surgery. Cystatin C enables glomerular filtration rate (GFR) to be estimated accurately and may be superior in this regard to creatinine-based estimates. We hypothesised, therefore, that cystatin C and derived estimates of GFR would independently predict long-term survival after cardiac surgery and would be superior in this respect to traditional estimates of GFR. The current study tests this hypothesis in a large and well-characterised cohort of patients. DESIGN: A prospective cohort study. SETTING: Regional cardiothoracic centre in Northeast Scotland. PARTICIPANTS: 1010 patients undergoing non-emergent cardiac surgery between 2004 and 2007. Serum creatinine and cystatin C levels were measured preoperatively and demographic and clinical variables were recorded. PRIMARY OUTCOME MEASURE: All-cause mortality, established from the National Records of Scotland. RESULTS: The median duration of follow-up after surgery was 9.7 years (IQR 8.9-10.6 years), during which 297 participants died. Preoperative creatinine and cystatin C levels and estimates of GFR derived from these were all strong predictors of death using Cox regression and remained independently predictive after adjustment for the logistic European System for Cardiac Operative Risk Evaluation, a well-validated clinical risk score and a range of other clinical predictors. Cystatin C-based measures were superior to creatinine-based estimates of GFR. CONCLUSIONS: Cystatin C and creatinine derived eGFR are powerful and independent predictors of long-term mortality following cardiac surgery. Estimates of GFR derived from cystatin C convey superior prognostic information to conventional creatinine-based estimates, but the observed differences are modest.

Assessment of functional capacity before major non-cardiac surgery: an international, prospective cohort study.

BACKGROUND: Functional capacity is an important component of risk assessment for major surgery. Doctors' clinical subjective assessment of patients' functional capacity has uncertain accuracy. We did a study to compare preoperative subjective assessment with alternative markers of fitness (cardiopulmonary exercise testing [CPET], scores on the Duke Activity Status Index [DASI] questionnaire, and serum N-terminal pro-B-type natriuretic peptide [NT pro-BNP] concentrations) for predicting death or complications after major elective non-cardiac surgery. METHODS: We did a multicentre, international, prospective cohort study at 25 hospitals: five in Canada, seven in the UK, ten in Australia, and three in New Zealand. We recruited adults aged at least 40 years who were scheduled for major non-cardiac surgery and deemed to have one or more risk factors for cardiac complications (eg, a history of heart failure, stroke, or diabetes) or coronary artery disease. Functional capacity was subjectively assessed in units of metabolic equivalents of tasks by the responsible anaesthesiologists in the preoperative assessment clinic, graded as poor (<4), moderate (4-10), or good (>10). All participants also completed the DASI questionnaire, underwent CPET to measure peak oxygen consumption, and had blood tests for measurement of NT pro-BNP concentrations. After surgery, patients had daily electrocardiograms and blood tests to measure troponin and creatinine concentrations until the third postoperative day or hospital discharge. The primary outcome was death or myocardial infarction within 30 days after surgery, assessed in all participants who underwent both CPET and surgery. Prognostic accuracy was assessed using logistic regression, receiver-operating-characteristic curves, and net risk reclassification. FINDINGS: Between March 1, 2013, and March 25, 2016, we included 1401 patients in the study. 28 (2%) of 1401 patients died or had a myocardial infarction within 30 days of surgery. Subjective assessment had 19·2% sensitivity (95% CI 14·2-25) and 94·7% specificity (93·2-95·9) for identifying the inability to attain four metabolic equivalents during CPET. Only DASI scores were associated with predicting the primary outcome (adjusted odds ratio 0·96, 95% CI 0·83-0·99; p=0·03). INTERPRETATION: Subjectively assessed functional capacity should not be used for preoperative risk evaluation. Clinicians could instead consider a measure such as DASI for cardiac risk assessment. FUNDING: Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, Ontario Ministry of Health and Long-Term Care, Ontario Ministry of Research, Innovation and Science, UK National Institute of Academic Anaesthesia, UK Clinical Research Collaboration, Australian and New Zealand College of Anaesthetists, and Monash University.

Measurement of Exercise Tolerance before Surgery (METS) study: a protocol for an international multicentre prospective cohort study of cardiopulmonary exercise testing prior to major non-cardiac surgery.

INTRODUCTION: Preoperative functional capacity is considered an important risk factor for cardiovascular and other complications of major non-cardiac surgery. Nonetheless, the usual approach for estimating preoperative functional capacity, namely doctors' subjective assessment, may not accurately predict postoperative morbidity or mortality. 3 possible alternatives are cardiopulmonary exercise testing; the Duke Activity Status Index, a standardised questionnaire for estimating functional capacity; and the serum concentration of N-terminal pro-B-type natriuretic peptide (NT pro-BNP), a biomarker for heart failure and cardiac ischaemia. METHODS AND ANALYSIS: The Measurement of Exercise Tolerance before Surgery (METS) Study is a multicentre prospective cohort study of patients undergoing major elective non-cardiac surgery at 25 participating study sites in Australia, Canada, New Zealand and the UK. We aim to recruit 1723 participants. Prior to surgery, participants undergo symptom-limited cardiopulmonary exercise testing on a cycle ergometer, complete the Duke Activity Status Index questionnaire, undergo blood sampling to measure serum NT pro-BNP concentration and have their functional capacity subjectively assessed by their responsible doctors. Participants are followed for 1 year after surgery to assess vital status, postoperative complications and general health utilities. The primary outcome is all-cause death or non-fatal myocardial infarction within 30 days after surgery, and the secondary outcome is all-cause death within 1 year after surgery. Both receiver-operating-characteristic curve methods and risk reclassification table methods will be used to compare the prognostic accuracy of preoperative subjective assessment, peak oxygen consumption during cardiopulmonary exercise testing, Duke Activity Status Index scores and serum NT pro-BNP concentration. ETHICS AND DISSEMINATION: The METS Study has received research ethics board approval at all sites. Participant recruitment began in March 2013, and 1-year follow-up is expected to finish in 2016. Publication of the results of the METS Study is anticipated to occur in 2017.

Comparison of sample types for N-terminal pro-B-type natriuretic peptide measured on the Siemens Immulite 2500 and Dimension Vista LOCI methods.

BACKGROUND: Measurement of serum natriuretic peptides is recommended in patients with suspected heart failure. Assays for N-terminal pro-B-type natriuretic peptide (NT-proBNP) are available on several platforms and can be measured in serum or heparinized plasma. Siemens Healthcare Diagnostics do not recommend the use of serum for the Immulite NT-proBNP assay. Serum offers some practical advantages over plasma. We investigated the suitability of serum for use with the Immulite and Dimension Vista LOCI methods. METHODS: Paired serum and heparinized plasma samples were drawn from patients in the Cardiology Department over a 48-h period. Samples spanning the NT-proBNP concentration range 50-60,000 ng/L were analysed using the Siemens Immulite 2500 and Dimension Vista LOCI methods. RESULTS: There was no significant difference between serum NT-proBNP concentrations on either platform (P = 0.0665). Plasma NT-proBNP measured using the Immulite were moderately higher than on Vista (P < 0.0001). There was a small but statistically significant difference between plasma and serum NT-proBNP measured using the Immulite (P = 0.0002) with plasma values higher than serum. A similar comparison between plasma and serum NT-proBNP measured using the Vista showed no difference (P = 0.3662). CONCLUSIONS: We have demonstrated the suitability of serum for use on the Immulite 2500. Bland-Altman comparative analysis indicated minimal bias between both serum methods near the clinical cut-off level below which heart failure is considered unlikely (400 ng/L) up to the highest concentration tested (60,000 ng/L).

A practical assessment of the short-term in vitro stability of troponin I at the 99 th percentile.

BACKGROUND: Serial troponin measurement is important for the diagnosis of myocardial infarction. As troponin concentrations approach the cut-off for detectable myocardial necrosis, smaller changes in troponin as a result of decreased in vitro stability may be sufficient to generate changes of apparent clinical significance. This is particularly relevant regarding retrospective 'add-on' testing on samples several hours after venepuncture. We investigated the stability of troponin I (cTnI) at values close to the 99th percentile limit. METHODS: Serum samples with baseline cTnI concentrations in the range 0.04-0.15 µg/L were analysed routinely using the Siemens TnI-Ultra assay. Follow-up analysis was carried out at 6, 9, 12, 24 and 48 h post-venepuncture after storage at room temperature and in the cold room. RESULTS: There was a significant decrease in cTnI concentration after 6 h post-venepuncture compared with baseline levels (P < 0.001). The maximum percentage change was -17.1% observed after 48 h storage at room temperature. Of samples with baseline cTnI concentration 0.040 µg/L, 80% had a cTnI concentration below 0.040 µg/L on re-analysis after 6 h. CONCLUSIONS: Requests for retrospective addition of troponin measurement on samples several hours after venepuncture is commonplace in many laboratories. Analysis of samples drawn >6 h previously may produce values below the cut-off for myocardial necrosis (0.040 µg/L) that would have been detectable if measured earlier as a result of decreased in vitro stability. Significant percentage decreases in cTnI concentration following storage may also have implications in lowering the threshold for an apparently clinically significant change to occur.

Randomised trial of glutamine, selenium, or both, to supplement parenteral nutrition for critically ill patients.

OBJECTIVE: To determine whether inclusion of glutamine, selenium, or both in a standard isonitrogenous, isocaloric preparation of parenteral nutrition influenced new infections and mortality among critically ill patients. DESIGN: Randomised, double blinded, factorial, controlled trial. SETTING: Level 2 and 3 (or combined) critical care units in Scotland. All 22 units were invited, and 10 participated. PARTICIPANTS: 502 adults in intensive care units and high dependency units for ≥ 48 hours, with gastrointestinal failure and requiring parenteral nutrition. INTERVENTIONS: Parenteral glutamine (20.2 g/day) or selenium (500 µg/day), or both, for up to seven days. MAIN OUTCOME MEASURES: Primary outcomes were participants with new infections in the first 14 days and mortality. An intention to treat analysis and a prespecified analysis of patients who received ≥ 5 days of the trial intervention are presented. Secondary outcomes included critical care unit and acute hospital lengths of stay, days of antibiotic use, and modified SOFA (Sepsis-related Organ Failure Assessment) score. RESULTS: Selenium supplementation did not significantly affect patients developing a new infection (126/251 v 139/251, odds ratio 0.81 (95% CI 0.57 to 1.15)), except for those who had received ≥ 5 days of supplementation (odds ratio 0.53 (0.30 to 0.93)). There was no overall effect of glutamine on new infections (134/250 v 131/252, odds ratio 1.07 (0.75 to 1.53)), even if patients received ≥ 5 days of supplementation (odds ratio 0.99 (0.56 to 1.75)). Six month mortality was not significantly different for selenium (107/251 v 114/251, odds ratio 0.89 (0.62 to 1.29)) or glutamine (115/250 v 106/252, 1.18 (0.82 to 1.70)). Length of stay, days of antibiotic use, and modified SOFA score were not significantly affected by selenium or glutamine supplementation. CONCLUSIONS: The primary (intention to treat) analysis showed no effect on new infections or on mortality when parenteral nutrition was supplemented with glutamine or selenium. Patients who received parenteral nutrition supplemented with selenium for ≥ 5 days did show a reduction in new infections. This finding requires confirmation. Trial registration Current Controlled Trials ISRCTN87144826.

Using the theory of planned behaviour as a process evaluation tool in randomised trials of knowledge translation strategies: A case study from UK primary care.

BACKGROUND: Randomised trials of knowledge translation strategies for professional behaviour change can provide robust estimates of effectiveness, but offer little insight into the causal mechanisms by which any change is produced. To illustrate the applicability of causal methods within randomised trials, we undertook a theory-based process evaluation study within an implementation trial to explore whether the cognitions of primary care doctors' predicted their test requesting behaviours and, secondly, whether the trial results were mediated by the theoretical constructs. METHODS: The process evaluation comprised a cross-sectional questionnaire survey of a random 50% sample of the randomised groups of primary care practices in Grampian (NHS Grampian), UK, who took part in a trial of the effect of enhanced feedback and brief educational reminders on test requesting behaviour. The process evaluation was based upon the Theory of Planned Behaviour and focussed on three of the test requesting behaviours that were targeted in the trial -- ferritin, follicle stimulating hormone (FSH), and Helicobacter Pylori serology (HPS). RESULTS: The questionnaire was completed by 131 primary care doctors (56%) from 42 (98%) of the sampled practices. Behavioural intention, attitude, and subjective norm were highly correlated for all the tests. There was no evidence that perceived behavioural control was correlated with any of the other measures. Simple linear regression analysis of the rate of test requests on minimum behavioural intentions had R2 of 11.1%, 12.5%, and 0.1% for ferritin, FSH, and HPS requesting, respectively. Mediational analysis showed that the trial results for ferritin and FSH were partially mediated (between 23% and 78% mediation) through intentions. The HPS trial result was not mediated through intention. CONCLUSIONS: This study demonstrated that a theory-based process evaluation can provide useful information on causal mechanisms that aid not only interpretation of the trial but also inform future evaluations and intervention development.

Noninvasive assessment of left ventricular filling pressure after acute myocardial infarction: a prospective study of the relative prognostic utility of clinical assessment, echocardiography, and B-type natriuretic peptide.

BACKGROUND: Elevated left ventricular filling pressure after acute myocardial infarction (AMI) may be identified using clinical assessment, echocardiography, and B-type natriuretic peptide (BNP) levels. All of these predict outcome in this setting. There are, however, no data assessing their relative prognostic value. The current study addresses this. METHODS: Four hundred patients underwent detailed echocardiography and measurement of BNP levels after AMI (median 1 day). The study end points were (1) a composite of death, recurrent AMI, and/or admission to hospital with heart failure within 1 year and (2) all-cause mortality during medium-term follow-up (median 2.9 years). RESULTS: Both an elevated ratio of early transmitral flow to early mitral annulus velocity (E/e') and higher BNP levels were associated with an increased risk of an adverse event within the first year (odds ratio 6.14 for E/e' >15, P < .001; odds ratio 1.19 per 50-pg/mL increase in BNP, P < .001) and medium-term mortality (hazard ratio 4.67 for E/e' >15, P < .001; hazard ratio 1.10 per 50-pg/mL increase in BNP, P < .001). Among patients with BNP levels higher than the median or in the upper quartile, an E/e' ratio >15 identified a subgroup at greatest risk of mortality (P < .001 for both). CONCLUSIONS: The E/e' ratio and BNP levels play important and complementary roles in the risk stratification of patients after AMI.

Usefulness of neutrophil/lymphocyte ratio as predictor of new-onset atrial fibrillation after coronary artery bypass grafting.

The neutrophil/lymphocyte (N/L) ratio integrates information on the inflammatory milieu and physiologic stress. It is an emerging marker of prognosis in patients with cardiovascular disease. We investigated the relation between the N/L ratio and postoperative atrial fibrillation (AF) in patients undergoing coronary artery bypass grafting. In a prospective cohort study, 275 patients undergoing nonemergency coronary artery bypass grafting were recruited. Patients with previous atrial arrhythmia or requiring concomitant valve surgery were excluded. The N/L ratio was determined preoperatively and on postoperative day 2. The study end point was AF lasting >30 seconds. Patients who developed AF (n = 107, 39%) had had a greater preoperative N/L ratio (median 3.0 vs 2.4, p = 0.001), but no differences were found in the other white blood cell parameters or C-reactive protein. The postoperative N/L ratio was greater in patients with AF (day 2, median 9.2 vs 7.2, p <0.001), and in multivariate models, a greater postoperative N/L ratio was independently associated with a greater incidence of AF (odds ratio 1.10 per unit increase, p = 0.003: odds ratio for N/L ratio >10.14 [optimal postoperative cutoff in our cohort], 2.83 per unit, p <0.001). Elevated pre- and postoperative N/L ratios were associated with an increased occurrence of AF after coronary artery bypass grafting. In conclusion, these results support an inflammatory etiology in postoperative AF but suggest that other factors are also important.

Use of preoperative natriuretic peptides and echocardiographic parameters in predicting new-onset atrial fibrillation after coronary artery bypass grafting: a prospective comparative study.

BACKGROUND: Atrial fibrillation (AF) is a common complication after coronary artery bypass grafting (CABG). We prospectively compared the ability of echocardiographic parameters and the cardiac neurohormones, brain natriuretic peptide (BNP), and N-terminal pro-brain natriuretic peptide (NT-proBNP) to predict AF in this setting. METHODS: We recruited 275 patients undergoing nonemergency CABG. Patients undergoing valve surgery or with prior atrial dysrhythmia (based on clinical history and review of medical records) were excluded. Echocardiography was performed, and natriuretic peptide levels were measured, 24 hours before surgery. The primary end point was postoperative AF lasting >30 seconds. RESULTS: The only significant echocardiographic predictors of postoperative AF (n = 107, 39%) were the transmitral E to A-wave ratio and the early mitral annulus velocity. Levels of BNP and NT-proBNP were higher in patients who developed AF. Both natriuretic peptides, but none of the echocardiographic parameters, remained independently predictive in multivariable analysis. The optimum cut points for predicting AF were 31 pg/mL for BNP (odds ratio [OR] 2.74, P = .001) and 74 pg/mL for NT-proBNP (OR 2.74, P = .003). CONCLUSION: Levels of BNP and NT-proBNP are independent, though modestly effective, predictors of AF after isolated CABG. In contrast, none of the echocardiographic parameters assessed, including measures of LV systolic function and filling pressure, were independently predictive.

Uric acid levels and outcome from coronary artery bypass grafting.

OBJECTIVE: Elevated uric acid levels have been associated with an adverse cardiovascular outcome in several settings. Their utility in patients undergoing surgical revascularization has not, however, been assessed. We hypothesized that serum uric acid levels would predict the outcome of patients undergoing coronary artery bypass grafting. METHODS: The study cohort consisted of 1140 consecutive patients undergoing nonemergency coronary artery bypass grafting. Clinical details were obtained prospectively, and serum uric acid was measured a median of 1 day before surgery. The primary end point was all-cause mortality. RESULTS: During a median of 4.5 years, 126 patients (11%) died. Mean (+/- standard deviation) uric acid levels were 390 +/- 131 micromol/L in patients who died versus 353 +/- 86 micromol/L among survivors (hazard ratio 1.48 per 100 micromol/L; 95% confidence interval, 1.25-1.74; P < .001). The excess risk associated with an elevated uric acid was particularly evident among patients in the upper quartile (>or=410 micromol/L; hazard ratio vs all other quartiles combined 2.18; 95% confidence interval, 1.53-3.11; P < .001). After adjusting for other potential prognostic variables, including the European System for Cardiac Operative Risk Evaluation, uric acid remained predictive of outcome. CONCLUSION: Increasing levels of uric acid are associated with poorer survival after coronary artery bypass grafting. Their prognostic utility is independent of other recognized risk factors, including the European System for Cardiac Operative Risk Evaluation.

The relationship between renal function and outcome from heart valve surgery.

BACKGROUND: The prognostic importance of renal function in patients undergoing surgery for valvular heart disease is poorly defined. The current study addresses this issue. METHODS: Baseline demographic and clinical variables, including the European system for cardiac operative risk evaluation (EuroSCORE), were recorded prospectively from 514 consecutive patients undergoing heart valve surgery between April 2000 and March 2004. Patients with active infective endocarditis and/or requiring emergency surgery were excluded. The glomerular filtration rate was estimated (eGFR) using the Modification of Diet in Renal Disease equation. The primary outcome was all-cause mortality. RESULTS: During a median follow-up of 2 years, 87 patients died. In univariable analysis, both eGFR (hazard ratio [HR] 0.69 per 10 mL/min per 1.73 m2, P<.001) and creatinine (HR 1.04 per 10 micromol/L, P<.001) predicted mortality. Estimated GFR was a stronger predictor and was used in subsequent multivariable models. It remained a powerful independent predictor of death in a multivariable model including all study variables (HR 0.70 per 10 mL/min per 1.73 m2 increase, P<.001) and in a model including EuroSCORE (HR 0.64 per 10 mL/min per 1.73 m2 increase, P<.001). After correction for preoperative EuroSCORE, an eGFR of <60 mL/min per 1.73 m2 was associated with an excess hazard of death of 2.31 (P=.001). CONCLUSION: Renal function, particularly the eGFR, is a powerful predictor of outcome in patients undergoing heart valve surgery. This prognostic utility is independent of other recognized risk factors and the EuroSCORE.

N-terminal pro B-type natriuretic peptide is an independent predictor of postoperative myocardial injury in patients undergoing major vascular surgery.

OBJECTIVE: Myocardial ischemia and infarction after surgery remain leading causes of morbidity and mortality in patients undergoing major vascular surgery. B-type natriuretic peptide has been shown to predict early postoperative cardiac events in patients undergoing major noncardiac surgery. We aimed to determine if N-terminal pro B-type natriuretic peptide (NT-pro-BNP), with its longer half-life and greater plasma stability, can predict postoperative myocardial injury in vascular patients. METHODS: Recruited were 136 patients undergoing elective surgery for subcritical limb ischemia or abdominal aortic aneurysm (AAA) repair. Plasma NT-pro-BNP was measured preoperatively, and troponin-I was measured immediately after surgery and on postoperative days 1, 2, 3, and 5. RESULTS: Twenty-eight patients (20%) sustained postoperative myocardial injury (troponin-I rise of >0.1 ng/mL). The median NT-pro-BNP level of those with myocardial injury was significantly higher than those who did not (380 pg/mL [interquartile range (IQR), 223-967] vs 209 pg/mL [109-363]; P = .003). NT-pro-BNP predicted this outcome with an area under the receiver operating characteristic (ROC) curve of 68% (95% confidence interval [CI] 0.56%-0.78%). In a multivariate analysis, a NT-pro-BNP value of >/=308 pg/mL (the optimal ROC curve-derived cutoff) was associated with an increased incidence of myocardial injury (odds ratio, 3.4; 95% CI, 1.41-9.09, P =.01). CONCLUSION: Elevated preoperative plasma NT-pro-BNP levels independently predict postoperative myocardial injury, which is associated with adverse outcome in the short- and long-term regardless of the presence of symptoms of acute coronary syndrome.

Preoperative neutrophil-lymphocyte ratio and outcome from coronary artery bypass grafting.

BACKGROUND: An elevated preoperative white blood cell count has been associated with a worse outcome after coronary artery bypass grafting (CABG). Leukocyte subtypes, and particularly the neutrophil-lymphocyte (N/L) ratio, may however, convey superior prognostic information. We hypothesized that the N/L ratio would predict the outcome of patients undergoing surgical revascularization. METHODS: Baseline clinical details were obtained prospectively in 1938 patients undergoing CABG. The differential leukocyte was measured before surgery, and patients were followed-up 3.6 years later. The primary end point was all-cause mortality. RESULTS: The preoperative N/L ratio was a powerful univariable predictor of mortality (hazard ratio [HR] 1.13 per unit, P < .001). In a backward conditional model, including all study variables, it remained a strong predictor (HR 1.09 per unit, P = .004). In a further model, including the European system for cardiac operative risk evaluation, the N/L ratio remained an independent predictor (HR 1.08 per unit, P = .008). Likewise, it was an independent predictor of cardiovascular mortality and predicted death in the subgroup of patients with a normal white blood cell count. This excess hazard was concentrated in patients with an N/L ratio in the upper quartile (>3.36). CONCLUSION: An elevated N/L ratio is associated with a poorer survival after CABG. This prognostic utility is independent of other recognized risk factors.

Utility of B-type natriuretic peptide in predicting medium-term mortality in patients undergoing major non-cardiac surgery.

This study was conducted to assess the ability of preoperative B-type natriuretic peptide levels to predict medium-term mortality in patients who undergo major noncardiac surgery. During a median of 654 days of follow-up, 33 patients from a total cohort of 204 patients (16%) died, 17 from cardiovascular causes. The optimal cutoff in this cohort, determined using a receiver-operating characteristic curve, was >35 pg . ml(-1). This was associated with a 3.5-fold increase in the hazard of death (p = 0.001) and a 6.9-fold increase in the hazard of cardiovascular mortality (p = 0.003). In conclusion, these findings extend recent work demonstrating that B-type natriuretic peptide levels obtained before major noncardiac surgery can be used to predict perioperative morbidity and indicate that they also forecast medium-term mortality, particularly cardiovascular death.

Randomised trial of glutamine and selenium supplemented parenteral nutrition for critically ill patients. Protocol Version 9, 19 February 2007 known as SIGNET (Scottish Intensive care Glutamine or seleNium Evaluative Trial).

BACKGROUND: Mortality rates in the Intensive Care Unit and subsequent hospital mortality rates in the UK remain high. Infections in Intensive Care are associated with a 2-3 times increased risk of death. It is thought that under conditions of severe metabolic stress glutamine becomes "conditionally essential". Selenium is an essential trace element that has antioxidant and anti-inflammatory properties. Approximately 23% of patients in Intensive Care require parenteral nutrition and glutamine and selenium are either absent or present in low amounts. Both glutamine and selenium have the potential to influence the immune system through independent biochemical pathways. Systematic reviews suggest that supplementing parenteral nutrition in critical illness with glutamine or selenium may reduce infections and mortality. Pilot data has shown that more than 50% of participants developed infections, typically resistant organisms. We are powered to show definitively whether supplementation of PN with either glutamine or selenium is effective at reducing new infections in critically ill patients. METHODS/DESIGN: 2 x 2 factorial, pragmatic, multicentre, double-blind, randomised controlled trial. The trial has an enrollment target of 500 patients. Inclusion criteria include: expected to be in critical care for at least 48 hours, aged 16 years or over, patients who require parenteral nutrition and are expected to have at least half their daily nutritional requirements given by that route. Allocation is to one of four iso-caloric, iso-nitrogenous groups: glutamine, selenium, both glutamine & selenium or no additional glutamine or selenium. Trial supplementation is given for up to seven days on the Intensive Care Unit and subsequent wards if practicable. The primary outcomes are episodes of infection in the 14 days after starting trial nutrition and mortality. Secondary outcomes include antibiotic usage, length of hospital stay, quality of life and cost-effectiveness. DISCUSSION: To date more than 285 patients have been recruited to the trial from 10 sites in Scotland. Recruitment is due to finish in August 2008 with a further six months follow up. We expect to report the results of the trial in summer 2009. TRIAL REGISTRATION: This trial is registered with the International Standard Randomised Controlled Trial Number system. ISRCTN87144826.

A cluster randomised controlled trial of educational prompts in diabetes care: study protocol.

BACKGROUND: Laboratory services have a central role in supporting screening, diagnosis, and management of patients. The increase in chronic disease management in primary care for conditions such as diabetes mellitus requires regular monitoring of patients' biochemical parameters. This process offers a route for improving the quality of care that patients receive by using test results as a vehicle for delivering educational messages as well as the test result itself. AIM: To develop and evaluate the effectiveness of a quality improvement initiative to improve the care of patients with diabetes using test report reminders. DESIGN: A programme of four cluster randomised controlled trials within one population of general practices. PARTICIPANTS: General practices in Newcastle-upon-Tyne, UK. INTERVENTION: Brief educational messages added to paper and electronic general practice laboratory test reports introduced over two phases. Phase One messages, attached to Haemoglobin A1c (HbA1c) reports, targeted glycaemic and cholesterol control. Phase Two messages, attached to albumin:creatinine ratio (ACR) reports, targeted blood pressure (BP) control and foot inspection. OUTCOMES: General practice mean levels of HbA1c and cholesterol (Phase One) and diastolic and systolic BP and proportions of patients having undergone foot inspections (Phase Two); number of tests requested.

Relationship between postoperative cardiac troponin I levels and outcome of cardiac surgery.

BACKGROUND: Cardiac surgery may be associated with significant perioperative and postoperative morbidity and mortality. Underlying pathology, surgical technique, and postoperative complications may all influence outcome. These factors may be reflected as a rise in postoperative troponin levels. Interpretation of troponin levels in this setting may therefore be complex. This study assessed the prognostic significance of such measurements, taking into account potential confounding variables. METHODS AND RESULTS: One-thousand three hundred sixty-five patients undergoing cardiac surgery underwent measurement of cardiac troponin I (cTnI) at 2 and 24 hours after surgery. The relationship of these measurements to subsequent mortality was established. After taking into account all other variables, cTnI levels measured at 24 hours were independently predictive of mortality at 30 days (odds ratio [OR] 1.14 per 10 microg/L, 95% confidence interval [CI] 1.05 to 1.24, P=0.002), 1 year (OR 1.10 per 10 microg/L, 95% CI 1.03 to 1.18, P=0.006), and 3 years (OR 1.07 per 10 microg/L, 95% CI 1.00 to 1.15, P=0.04). Cardiac TnI levels in the highest quartile at 24 hours were associated with a particularly poor outcome. CONCLUSIONS: cTnI levels measured 24 hours after cardiac surgery predict short-, medium-, and long-term mortality and remain independently predictive when adjusted for all other potentially confounding variables, including operation complexity.