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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. 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. 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). An elevated N/L ratio is associated with a poorer survival after CABG. This prognostic utility is independent of other recognized risk factors.

In a prospective evaluation of 50 ED patients with suspected MI, we demonstrated very good correlation between the Atellica VTLi POC hs-cTnI and the Abbott Alinity laboratory hs-cTnI tests. Clinicians will have to consider the benefit of faster results (nearly an hour with POC testing) against identification of more low-risk patients (threefold in this evaluation) with a laboratory assay. Ethics approval This study involves human participants and was approved by After Institutional Research Governance review this project was registered as a service evaluation (ID 5721).

ObjectiveRenal 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.DesignA prospective cohort study.SettingRegional cardiothoracic centre in Northeast Scotland.Participants1010 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 measureAll-cause mortality, established from the National Records of Scotland.ResultsThe 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.ConclusionsCystatin 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.

BackgroundGallstone disease (cholelithiasis) is common. In most people it is asymptomatic and does not require treatment, but in about 20% it can become symptomatic, causing pain and other complications requiring medical attention and/or surgery. A proportion of symptomatic people with uncomplicated gallstone disease do not experience further episodes of pain and, therefore, could be treated conservatively. Moreover, surgery carries risks of perioperative and postoperative complications.Methods and analysisC-Gall is a pragmatic, multicentre, randomised controlled trial and economic evaluation to assess whether cholecystectomy is cost-effective compared with observation/ conservative management (here after referred to as medical management) at 18 months post-randomisation (with internal pilot).Primary outcome measurePatient-reported quality of life (QoL) (36-Item Short Form Survey (SF-36) bodily pain domain) up to 18 months after randomisation.The primary economic outcome is incremental cost per quality-adjusted life year gained at 18 months.Secondary outcome measuresSecondary outcome measures include condition-specific QoL, SF-36 domains, complications, further treatment, persistent symptoms, healthcare resource use, and costs assessed at 18 and 24 months after randomisation. The bodily pain domain of the SF-36 will also be assessed at 24 months after randomisation.A sample size of 430 participants was calculated. Computer-generated 1:1 randomisation was used.The C-Gall Study is currently in follow-up in 20 UK research centres. The first patient was randomised on 1 August 2016, with follow-up to be completed by 30 November 2021.Statistical analysisStatistical analysis of the primary outcome will be intention-to-treat and a per-protocol analysis. The primary outcome, area under the curve (AUC) for the SF-36 bodily pain up to 18 months, will be generated using the Trapezium rule and analysed using linear regression with adjustment for the minimisation variables (recruitment site, sex and age). For the secondary outcome, SF-36 bodily pain, AUC up to 24 months will be analysed in a similar way. Other secondary outcomes will be analysed using generalised linear models with adjustment for minimisation and baseline variables, as appropriate. Statistical significance will be at the two-sided 5% level with corresponding CIs.Ethics and disseminationThe North of Scotland Research Ethics Committee approved this study (16/NS/0053). The dissemination plans include Health Technology Assessment monograph, international scientific meetings and publications in high-impact, open-access journals.Trial registration numberISRCTN55215960; pre-results.

BackgroundMany completed trials of interventions for uncomplicated gallstone disease are not as helpful as they could be due to lack of standardisation across studies, outcome definition, collection and reporting. This heterogeneity of outcomes across studies hampers useful synthesis of primary studies and ultimately negatively impacts on decision making by all stakeholders. Core outcome sets offer a potential solution to this problem of heterogeneity and concerns over whether the ‘right’ outcomes are being measured. One of the first steps in core outcome set generation is to identify the range of outcomes reported (in the literature or by patients directly) that are considered important.ObjectivesTo develop a systematic map that examines the variation in outcome reporting of interventions for uncomplicated symptomatic gallstone disease, and to identify other outcomes of importance to patients with gallstones not previously measured or reported in interventional studies.ResultsThe literature search identified 794 potentially relevant titles and abstracts of which 137 were deemed eligible for inclusion. A total of 129 randomised controlled trials, 4 gallstone disease specific patient-reported outcome measures (PROMs) and 8 qualitative studies were included. This was supplemented with data from 6 individual interviews, 1 focus group (n=5 participants) and analysis of 20 consultations. A total of 386 individual recorded outcomes were identified across the combined evidence: 330 outcomes (which were reported 1147 times) from trials evaluating interventions, 22 outcomes from PROMs, 17 outcomes from existing qualitative studies and 17 outcomes from primary qualitative research. Areas of overlap between the evidence sources existed but also the primary research contributed new, unreported in this context, outcomes.ConclusionsThis study took a rigorous approach to catalogue and map the outcomes of importance in gallstone disease to enhance the development of the COS ‘long’ list. A COS for uncomplicated gallstone disease that considers the views of all relevant stakeholders is needed.

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

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 R 2 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.

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. 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. 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). 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.

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. 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). 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). The E/ e' ratio and BNP levels play important and complementary roles in the risk stratification of patients after AMI.

Laboratory services play an important part in screening, diagnosis, and management of patients within primary care. However, unnecessary use of laboratory tests is increasing. Our aim was to assess the effect of two interventions on the number of laboratory tests requested by primary-care physicians. We did a cluster randomised controlled trial using a 2×2 factorial design, involving 85 primary-care practices (370 family practitioners) that request all laboratory tests from one regional centre. The interventions were quarterly feedback of practice requesting rates for nine laboratory tests, enhanced with educational messages, and brief educational reminder messages added to the test result reports for nine laboratory tests. The primary outcome was the number of targeted tests requested by primary-care practices during the 12 months of the intervention. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN06490422. Practices that received either or both the enhanced feedback and the reminder messages were significantly less likely than the control group to request the targeted tests in total (enhanced feedback odds ratio 0·87, 95% CI 0·81–0·94; reminder messages 0·89, 0·83–0·93). The effect of the interventions varied across the targeted tests individually, although the number of tests requested for both interventions was generally reduced. Neither intervention was consistently better than the other. Enhanced feedback of requesting rates and brief educational reminder messages, alone and in combination, are effective strategies for reducing test requesting in primary care. Both strategies are feasible within most laboratory settings.