Domenico Pagano

Worldwide Clinical Trials, Nottigham, England, United Kingdom

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Publications (44)248.69 Total impact

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    ABSTRACT: Little is known regarding the steady-state uptake of drugs into the human myocardium. Perhexiline is a prophylactic anti-anginal drug which is increasingly also used in the treatment of heart failure and hypertrophic cardiomyopathy. We explored the relationship between plasma perhexiline concentrations and its uptake into the myocardium. Blood, right atrium ± left ventricle biopsies were obtained from patients treated with perhexiline for a median of 8.5 days before undergoing coronary surgery in the perhexiline arm of a randomised controlled trial. Perhexiline concentrations in plasma and heart tissue were determined by HPLC. Atrial biopsies were obtained from 94 patients and ventricular biopsies from 28 patients. The median plasma perhexiline concentration was within the therapeutic range at 0.24mg/L (IQR 0.12-0.44), the median atrial concentration was 6.02mg/Kg (IQR 2.70-9.06) and median ventricular concentration was 10.0mg/Kg (IQR 5.76-13.1). Atrial (R(2) 0.76) and ventricular (R(2) 0.73) perhexiline concentrations were closely and directly correlated with plasma concentrations (both p<0.001). The median atrial:plasma ratio was 21.5 (IQR 18.1-27.1), ventricular:plasma ratio was 34.9 (IQR 24.5-55.2) and ventricular:atrial ratio was 1.67 (IQR 1.39-2.22). Using multiple regression, the best model for predicting steady-state atrial concentration included plasma perhexiline, heart rate and age (R(2) 0.83). Ventricular concentrations were directly correlated with plasma perhexiline concentration and length of therapy (R(2) 0.84). This study demonstrates that plasma perhexiline concentrations are predictive of myocardial drug concentrations, a major determinant of drug effect. However, net myocardial perhexiline uptake is significantly modulated by patient age, potentially via alteration of myocardial:extracardiac drug uptake.
    British Journal of Clinical Pharmacology 10/2013; · 3.58 Impact Factor
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    ABSTRACT: In 2010, the Department of Health in England introduced an incentivised national target for National Health Service (NHS) hospitals aiming to increase the number of patients assessed for the risk of developing venous thromboembolism (VTE) associated with hospital admission. We assessed the impact of this initiative on VTE mortality and subsequent readmission with non-fatal VTE. Observational cohort study. All patients admitted to NHS hospitals in England between July 2010 and March 2012. An NHS hospital which assessed at least 90% of patient admissions achieved the quality standard. The principal outcome measured was death from VTE up till 90 days after hospital discharge using linked Office of National Statistics and Hospital Episode Statistics data. In the principal analyses of patients admitted to hospital for more than 3 days, there was a statistically significant reduction in VTE deaths in hospitals achieving 90% VTE risk assessment: relative risk (RR) 0.85 (95% CI 0.75 to 0.96; p=0.011) for VTE as the primary cause of death. In supportive analyses of postdischarge deaths after index admissions of up to 3 days, there was also a reduction in fatal VTE RR 0.61 (0.48 to 0.79; p=0.0002). This effect was seen for both surgical and non-surgical patients. No effect was seen in day case admissions. There was no change in non-fatal VTE readmissions up to 90 days after discharge. A national quality initiative to increase the number of hospitalised patients assessed for risk of VTE has resulted in a reduction in VTE mortality.
    Heart (British Cardiac Society) 09/2013; · 5.01 Impact Factor
  • Domenico Pagano, Nick Freemantle
    The Journal of thoracic and cardiovascular surgery 09/2013; 146(3):732. · 3.41 Impact Factor
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    ABSTRACT: Continuous monitoring of surgical outcomes through benchmarking and the identification of best practices has become increasingly important. A structured approach to data collection, coupled with validation, analysis and reporting, is a powerful tool in these endeavours. However, inconsistencies in standards and practices have made comparisons within and between European countries cumbersome. The European Association for Cardio-Thoracic Surgery (EACTS) has established a large international database with the goals of (i) working with other organizations towards universal data collection and creating a European-wide repository of information on the practice of cardio-thoracic surgery, and (ii) disseminating that information in scientific, peer-reviewed articles. We report on the process of data collection, as well as on an overview of the data in the database. The EACTS Database Committee met for the first time in Monaco, September 2002, to establish the ground rules for the process of setting up the database. Subsequently, data have been collected and merged by Dendrite Clinical Systems Ltd. As of December 2008, the database included 1 074 168 patient records from 366 hospitals located in 29 countries. The latest submission from the years 2006-08 included 404 721 records. The largest contributors were the UK (32.0%), Germany (20.9%) and Belgium (7.3%). Isolated coronary bypass surgery was the most frequently performed operation; the proportion of surgical workload that comprised isolated coronary artery bypass grafting varied from country to country: 30% in Spain and almost 70% in Denmark. Isolated valve procedures constituted 12% of all procedures in Norway and 32% in Spain. Baseline demographics showed an increase in the mean age and the percentage of patients that were female over time. Remarkably, the mortality rates for all procedures declined over the period analysed, to 2.2% (95% confidence interval [CI] 2.2-2.3%) for isolated coronary bypass, 3.4% (95% CI 3.3-3.5%) for isolated valve and 6.2% (95% CI 6.0-6.5%) for bypass + valve procedures. The EACTS database has proven to be an important step forward in providing opportunities for monitoring cardiac surgical care across Europe. As the database continues to expand, it will facilitate research projects, establish benchmarking standards and identify potential areas for quality improvements.
    European journal of cardio-thoracic surgery: official journal of the European Association for Cardio-thoracic Surgery 06/2013; · 2.40 Impact Factor
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    ABSTRACT: OBJECTIVES: Prediction of operative risk in adult patients undergoing cardiac surgery remains a challenge, particularly in high-risk patients. In Europe, the EuroSCORE is the most commonly used risk-prediction model, but is no longer accurately calibrated to be used in contemporary practice. The new EuroSCORE II was recently published in an attempt to improve risk prediction. We sought to assess the predictive value of EuroSCORE II compared with the original EuroSCOREs in high-risk patients. METHODS: Patients who underwent surgery between 1 April 2006 and 31 March 2011 with a preoperative logistic EuroSCORE ≥10 were identified from prospective cardiac surgical databases at two European institutions. Additional variables included in EuroSCORE II, but not in the original EuroSCORE, were retrospectively collected through patient chart review. The C-statistic to predict in-hospital mortality was calculated for the additive EuroSCORE, logistic EuroSCORE and EuroSCORE II models. The Hosmer-Lemeshow test was used to assess model calibration by comparing observed and expected mortality in a number of risk strata. The fit of EuroSCORE II was compared with the original EuroSCOREs using Akaike's Information Criterion (AIC). RESULTS: A total of 933 patients were identified; the median additive EuroSCORE was 10 (interquartile range [IQR] 9-11), median logistic EuroSCORE 15.3 (IQR 12.0-24.1) and median EuroSCORE II 9.3 (5.8-15.6). There were 90 (9.7%) in-hospital deaths. None of the EuroSCORE models performed well with a C-statistic of 0.67 for the additive EuroSCORE and EuroSCORE II, and 0.66 for the logistic EuroSCORE. Model calibration was poor for the EuroSCORE II (chi-square 16.5; P = 0.035). Both the additive EuroSCORE and logistic EuroSCORE had a numerically better model fit, the additive EuroSCORE statistically significantly so (difference in AIC was -5.66; P = 0.017). CONCLUSIONS: The new EuroSCORE II does not improve risk prediction in high-risk patients undergoing adult cardiac surgery when compared with original additive and logistic EuroSCOREs. The key problem of risk stratification in high-risk patients has not been addressed by this new model. Future iterations of the score should explore more advanced statistical methods and focus on developing procedure-specific algorithms. Moreover, models that predict complications in addition to mortality may prove to be of increasing value.
    European journal of cardio-thoracic surgery: official journal of the European Association for Cardio-thoracic Surgery 03/2013; · 2.40 Impact Factor
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    ABSTRACT: OBJECTIVES: Risk prediction in adult patients undergoing cardiac surgery remains inaccurate and should be further improved. Therefore, we aimed to identify risk factors that are predictive of mortality, stroke, renal failure and/or length of stay after adult cardiac surgery in contemporary practice. METHODS: We searched the Medline database for English-language original contributions from January 2000 to December 2011 to identify preoperative independent risk factors of one of the following outcomes after adult cardiac surgery: death, stroke, renal failure and/or length of stay. Two investigators independently screened the studies. Inclusion criteria were (i) the study described an adult cardiac patient population; (ii) the study was an original contribution; (iii) multivariable analyses were performed to identify independent predictors; (iv) ≥1 of the predefined outcomes was analysed; (v) at least one variable was an independent predictor, or a variable was included in a risk model that was developed. RESULTS: The search yielded 5768 studies. After the initial title screening, a second screening of the full texts of 1234 studies was performed. Ultimately, 844 studies were included in the systematic review. In these studies, we identified a large number of independent predictors of mortality, stroke, renal failure and length of stay, which could be categorized into variables related to: disease pathology, planned surgical procedure, patient demographics, patient history, patient comorbidities, patient status, blood values, urine values, medication use and gene mutations. Many of these variables are frequently not considered as predictive of outcomes. CONCLUSIONS: Risk estimates of mortality, stroke, renal failure and length of stay may be improved by the inclusion of additional (non-traditional) innovative risk factors. Current and future databases should consider collecting these variables.
    European journal of cardio-thoracic surgery: official journal of the European Association for Cardio-thoracic Surgery 02/2013; · 2.40 Impact Factor
  • The Journal of thoracic and cardiovascular surgery 02/2013; 145(2):610-1. · 3.41 Impact Factor
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    ABSTRACT: Clinical registries will have an increasingly important role to play in health-care, with a number already established in cardiac surgery. This review covers the fundamentals of establishing and managing clinical registries, including legal and ethical frameworks along with intellectual property attribution. Also discussed are important issues relating to the processing of data, data extraction and conducting analyses using registry data.
    European journal of cardio-thoracic surgery: official journal of the European Association for Cardio-thoracic Surgery 01/2013; · 2.40 Impact Factor
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    ABSTRACT: OBJECTIVE: To advance methods for the estimation of hospital performance based upon mortality ratios. DESIGN: Observational study estimating trust performance in a year derived according to comparative standards from a 3-year period, accounting for patient-level case-mix and overdispersion (unexplained variability). PARTICIPANTS: 23 363 630 admissions to the English National Health Service (NHS) by NHS Trust. MAIN OUTCOME MEASURES: Number of SDs (QUality and Outcomes Research Unit Measure, QUORUM banding) and comparative odds of hospital mortality difference from mean performance by trust compared for 2010/2011, 2008/2009 and 2009/2010, accounting for patient-level case-mix. RESULTS: The model was highly predictive of mortality (C statistic=0.93), and well calibrated by risk stratum. There was substantial overdispersion. No trusts were more than 3 SDs above the mean, and only one trust was more than 2 SDs above the mean for 2010/2011. CONCLUSIONS: QUORUM is highly predictive of patient mortality in hospital or up to 30 days after admission. However, like the Summary Hospital Mortality Indicator (SHMI), QUORUM is subjected to considerable remaining legitimate but unexplained variation. It is unlikely that measures like QUORUM and SHMI will be useful beyond identifying a very small number of trusts as potential outliers.
    BMJ Open 01/2013; 3(1). · 1.58 Impact Factor
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    ABSTRACT: OBJECTIVES: Progressive loss of calibration of the original EuroSCORE models has necessitated the introduction of the EuroSCORE II model. Poor model calibration has important implications for clinical decision-making and risk adjustment of governance analyses. The objective of this study was to explore the reasons for the calibration drift of the logistic EuroSCORE. METHODS: Data from the Society for Cardiothoracic Surgery in Great Britain and Ireland database were analysed for procedures performed at all National Health Service and some private hospitals in England and Wales between April 2001 and March 2011. The primary outcome was in-hospital mortality. EuroSCORE risk factors, overall model calibration and discrimination were assessed over time. RESULTS: A total of 317 292 procedures were included. Over the study period, mean age at surgery increased from 64.6 to 67.2 years. The proportion of procedures that were isolated coronary artery bypass grafts decreased from 67.5 to 51.2%. In-hospital mortality fell from 4.1 to 2.8%, but the mean logistic EuroSCORE increased from 5.6 to 7.6%. The logistic EuroSCORE remained a good discriminant throughout the study period (area under the receiver-operating characteristic curve between 0.79 and 0.85), but calibration (observed-to-expected mortality ratio) fell from 0.76 to 0.37. Inadequate adjustment for decreasing baseline risk affected calibration considerably. DISCUSSIONS: Patient risk factors and case-mix in adult cardiac surgery change dynamically over time. Models like the EuroSCORE that are developed using a 'snapshot' of data in time do not account for this and can subsequently lose calibration. It is therefore important to regularly revalidate clinical prediction models.
    European journal of cardio-thoracic surgery: official journal of the European Association for Cardio-thoracic Surgery 11/2012; · 2.40 Impact Factor
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    ABSTRACT: OBJECTIVES: Aortic valve replacement (AVR) is accepted as the standard treatment for severe symptomatic aortic valve stenosis and regurgitation. As novel treatments are introduced for patients at high risk for conventional surgery, it is important to have models that accurately predict procedural risk. The aim of this study was to develop and validate a risk-stratification model to predict in-hospital risk of death for patients undergoing AVR and to compare the model with existing algorithms. METHODS: We reviewed data from the Central Cardiac Adult Database, which holds prospectively collected clinical information on all adult patients undergoing cardiac surgery in National Health Service (NHS) hospitals and some private providers in the UK and Ireland. We included all the patients undergoing AVR with or without coronary artery bypass grafting. The study population consists of 55 157 patients undergoing surgery between 1 April 2001 and 31 March 2009. The model was built using data from April 2001 to March 2008 and validated using data from patients undergoing surgery from April 2008 to March 2009. The model was compared against the additive and logistic EuroSCORE models and a valve-specific risk-prediction model. RESULTS: The final multivariable model includes items describing cardiovascular risk status and procedural factors. Applying the model to the independent validation dataset provided a c-statistic (index of rank correlation) of 0.791, which was substantially better than that achieved by previously developed risk models in Europe, and significantly improved risk prediction in higher-risk patients. CONCLUSIONS: We have produced an accurate risk model to predict outcome following AVR surgery. It will be of use for patient selection and informed consent, and of particular interest in defining those patients at high risk who may benefit from novel approaches to AVR.
    European journal of cardio-thoracic surgery: official journal of the European Association for Cardio-thoracic Surgery 08/2012; · 2.40 Impact Factor
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    ABSTRACT: The original EuroSCORE models are poorly calibrated for predicting mortality in contemporary cardiac surgery. EuroSCORE II has been proposed as a new risk model. The objective of this study was to assess the performance of EuroSCORE II in UK cardiac surgery. A cross-sectional analysis of prospectively collected multi-centre clinical audit data, from the Society for Cardiothoracic Surgery in Great Britain and Ireland Database. All NHS hospitals, and some UK private hospitals performing adult cardiac surgery. 23 740 procedures at 41 hospitals between July 2010 and March 2011. The main outcome measure was in-hospital mortality. Model calibration (Hosmer-Lemeshow test, calibration plot) and discrimination (area under receiver operating characteristic curve) were assessed in the overall cohort and clinically defined sub-groups. The mean age at procedure was 67.1 years (SD 11.8) and 27.7% were women. The overall mortality was 3.1% with a EuroSCORE II predicted mortality of 3.4%. Calibration was good overall but the model failed the Hosmer-Lemeshow test (p=0.003) mainly due to over-prediction in the highest and lowest-risk patients. Calibration was poor for isolated coronary artery bypass graft surgery (Hosmer-Lemeshow, p<0.001). The model had good discrimination overall (area under receiver operating characteristic curve 0.808, 95% CI 0.793 to 0.824) and in all clinical sub-groups analysed. EuroSCORE II performs well overall in the UK and is an acceptable contemporary generic cardiac surgery risk model. However, the model is poorly calibrated for isolated coronary artery bypass graft surgery and in both the highest and lowest risk patients. Regular revalidation of EuroSCORE II will be needed to identify calibration drift or clinical inconsistencies, which commonly emerge in clinical prediction models.
    Heart (British Cardiac Society) 08/2012; 98(21):1568-72. · 5.01 Impact Factor
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    ABSTRACT: OBJECTIVE: Meta-analysis of small, randomized, placebo-controlled trials demonstrated efficacy and safety of aprotinin. After highly publicized retrospective studies and the early stopping of the Blood Conservation Using Antifibrinolytics in a Randomized Trial (BART), aprotinin was withdrawn. We conducted a new meta-analysis (including BART) on safety and efficacy of aprotinin in cardiac surgery. METHODS: We conducted a mixed treatment comparisons network meta-analysis estimating the effects of aprotinin and alternative agents in reducing blood loss during surgery. We implemented a combination of direct and indirect evidence in mixed treatment comparisons and estimated relative effects for different agents on all-cause mortality and return to the operating room for bleeding and conducted a supportive analysis of the effects of different agents with only directly randomized trials. RESULTS: Mixed treatment analysis of 88 trials randomizing 15,528 patients to 1 of 3 antifibrinolytic agents demonstrated no difference in mortality between placebo and antifibrinolytic agents. Analysis of aprotinin versus tranexamic acid and ε-aminocaproic acid in 17 and 6 trials, respectively and tranexamic acid versus ε-aminocaproic acid in 5 trials demonstrated no difference in mortality between treatment allocations. All agents were superior to placebo in reducing reexploration for bleeding, with aprotinin numerically superior: aprotinin odds ratio, 2.6 (95% confidence interval, 1.9-3.7); tranexamic acid odds ratio, 1.79 (1.2-2.9), and ε-aminocaproic acid odds ratio, 2.4 (1.3-6.6). CONCLUSIONS: This mixed treatment comparisons meta-analysis demonstrates no increased mortality risk with aprotinin versus other antifibrinolytic agents. All agents were superior to placebo in reducing reexploration for bleeding after adult cardiac surgery.
    The Journal of thoracic and cardiovascular surgery 08/2012; · 3.41 Impact Factor
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    ABSTRACT: To determine the predictors of post-operative renal function following adult cardiac surgery, and to assess the influence of this on late survival. Prospectively collected data were analysed on 8032 patients who underwent coronary artery bypass grafting, valve surgery or combined procedures from 1 January 1998 until 31 December 2008, who did not require preoperative renal replacement therapy. The estimated glomerular filtration rate (eGFR) was calculated by the Modification of Diet in Renal Disease formula accounting for ethnicity pre-operatively, post-operatively on the fourth post-operative day, and the post-operative nadir based upon the peak post-operative creatinine within 30 days of surgery. Late survival data were obtained from the UK Central Cardiac Audit Database (CCAD). Appropriate frailty analyses were conducted in R and model fit was compared using Aikaike's Information Criterion. Initial analysis intended to determine predictors of post-operative renal function including pre-operative eGFR, EuroSCORE and surgical procedure including the operative procedure and bypass time. Further analysis examined its influence on late survival. Median follow-up was 72 months (IQR 48-105) during which there were 904 late deaths. The most powerful predictor of the day 4 eGFR was the pre-operative eGFR but other factors contributed including increasing EuroSCORE and bypass time. The pre-operative eGFR was shown to be a strong and independent predictor of late outcome (P = 0.0001, HR 0.497 95%CI 0.434-564); however, model fit was significantly improved using the day 4 eGFR (P = 0.0001, HR 0.43 95%CI 0.385-0.482). No specific change in individual renal function was identified as a predictor of adverse late survival, and neither the pre-operative nor day 4 eGFR was predictive of the nadir of renal function. Subtle early changes in renal function at the time of surgery are powerful predictors of adverse late outcome and can be predicted by pre-operative renal function.
    European journal of cardio-thoracic surgery: official journal of the European Association for Cardio-thoracic Surgery 04/2012; 41(4):e38-42. · 2.40 Impact Factor
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    ABSTRACT: Although the presentation of original research to learned societies is valuable, the target should be publication in a peer-reviewed journal. Therefore, the strength of a meeting may be assessed by the rate of the subsequent publication of papers from the presented abstracts. We conducted an analysis of abstracts presented at consecutive annual meetings of the Society for Cardiothoracic Surgery (SCTS) in Great Britain and Ireland over a 15-year period. Abstract books and other documentation from the 1993-2007 meetings were reviewed; abstracts from other major Cardiothoracic Surgery meetings held in 2007 were also reviewed. Medline was searched to identify the peer-reviewed publications arising from each work presented. For abstracts presented at SCTS in 2003-07, the factors potentially associated with publication were analysed by logistic regression. If no publications were identified, authors were contacted through a standardized email questionnaire to ascertain its status and reasons for non-publication. Over the 15-year period, 909 abstracts were presented at the SCTS meetings. The rate of publication rose from ∼30% in the mid-1990s to consistently >60% from recent meetings, with a high of 81.3% from 2006. However, in comparison with other Cardiothoracic Surgery meetings in 2007, the chance of subsequent publication from SCTS (66.7%) was lower than from the European Association for Cardio-Thoracic Surgery (75.0%), the American Association for Thoracic Surgery (83.9%) and The Society of Thoracic Surgeons (72.5%) meetings. For abstracts presented at the last five SCTS meetings, publication was most commonly in a speciality journal (56.3%) and the median time for publication was 15 months (range -24 to 63 months) with 14 papers published prior to presentation at the meeting. On regression analysis, the only factor associated with publication was the study design comparing randomized trials and systematic reviews with other types of study (P < 0.01). Of the 90 unpublished abstracts, 48 (53.3%) authors replied to an email questionnaire revealing that 41 (85.4%) were never submitted for publication. The most common reasons given were low priority (29.6%) and low likelihood of acceptance (24.1%). In recent years, the annual meeting of the Society has become a forum for the presentation of high-quality research that usually withstands peer-review, most commonly in a speciality journal. The rate of publication has increased to consistently >60%, although those that remain unpublished are generally never submitted. This compares favourably with national meetings of other surgical societies, although it is lower than other major cardiothoracic meetings which have an affiliated journal. At a time when it has been suggested that medical research in the UK is in decline, cardiothoracic surgery appears to be thriving.
    European journal of cardio-thoracic surgery: official journal of the European Association for Cardio-thoracic Surgery 03/2012; 42(5):885-9. · 2.40 Impact Factor
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    ABSTRACT: The Global Registry of Acute Coronary Events (GRACE) registry reported that the in-hospital risk of death from non-ST elevation myocardial infarction (NSTEMI) is 5%, with an 11% mortality by 6 months. Prospective Registry of Acute Ischaemic Syndromes in the UK demonstrated that the overall risk of death from NSTEMI over 4 years is 25%. In GRACE, while 28% of patients received percutaneous intervention, only 10% received coronary artery bypass graft (CABG). Results of urgent CABG surgery following NSTEMI are difficult to interpret as these often include patients who have had STEMIs and urgent surgery. With increasing multidisciplinary assessment of patients with acute coronary syndromes (ACS), accurate data collection on the outcome of such patients could inform correct revascularization strategy. Three hundred and forty-two consecutive patients who had undergone urgent CABG from April 2004 to April 2009 at a single institution were identified. The GRACE predicted mortality was calculated from hospital records and patients categorized into three groups based upon their predicted risk. Late survival data were obtained from the UK Office of National Statistics. The GRACE score could be calculated in 270 patients with a confirmed diagnosis of NSTEMI. Of the 304 probable patients with NSTEMI, there were 5 in-hospital deaths (1.6%). Survival at 6 months was higher than GRACE predicted mortality in all groups. At 6 months the predicted versus observed mortality in the low-risk group was 4 versus 2% (P = 0.05), in the medium-risk group it was 12.5 versus 1.9% (P = 0.0001) and in the high-risk group it was 25 versus 20% (P = 0.45). In-hospital CABG performed after NSTEMI is associated with a low-mortality risk and survival significantly better than that predicted by the GRACE score.
    European journal of cardio-thoracic surgery: official journal of the European Association for Cardio-thoracic Surgery 02/2012; 41(5):e87-91; discussion e91-2. · 2.40 Impact Factor
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    ABSTRACT: To assess whether weekend admissions to hospital and/or already being an inpatient on weekend days were associated with any additional mortality risk. Retrospective observational survivorship study. We analysed all admissions to the English National Health Service (NHS) during the financial year 2009/10, following up all patients for 30 days after admission and accounting for risk of death associated with diagnosis, co-morbidities, admission history, age, sex, ethnicity, deprivation, seasonality, day of admission and hospital trust, including day of death as a time dependent covariate. The principal analysis was based on time to in-hospital death. National Health Service Hospitals in England. 30 day mortality (in or out of hospital). There were 14,217,640 admissions included in the principal analysis, with 187,337 in-hospital deaths reported within 30 days of admission. Admission on weekend days was associated with a considerable increase in risk of subsequent death compared with admission on weekdays, hazard ratio for Sunday versus Wednesday 1.16 (95% CI 1.14 to 1.18; P < .0001), and for Saturday versus Wednesday 1.11 (95% CI 1.09 to 1.13; P < .0001). Hospital stays on weekend days were associated with a lower risk of death than midweek days, hazard ratio for being in hospital on Sunday versus Wednesday 0.92 (95% CI 0.91 to 0.94; P < .0001), and for Saturday versus Wednesday 0.95 (95% CI 0.93 to 0.96; P < .0001). Similar findings were observed on a smaller US data set. Admission at the weekend is associated with increased risk of subsequent death within 30 days of admission. The likelihood of death actually occurring is less on a weekend day than on a mid-week day.
    Journal of the Royal Society of Medicine 02/2012; 105(2):74-84. · 1.72 Impact Factor
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    ABSTRACT: Various troponin I measurements (troponometrics) have been used as surrogate markers of patient outcome after coronary artery bypass grafting (CABG). Our aim was to define the postoperative troponometric best able to predict in-hospital and late mortality. In 440 patients (seen from January 2000 to September 2004) undergoing isolated on-pump CABG with standardized anesthesia, perfusion, cardioplegia, and postoperative care, we followed all-cause mortality (census June 2009, 100% complete). Subjects underwent troponin I (cardiac troponin I [cTnI]) estimation at baseline and 6, 12, 24, 48, and 72 hours postoperatively, and individual time-point cTnI (T6, T12, T24, T48, T72), peak cTnI (Cmax), increase in cTnI between 6 and 12 hours (T↑6-12) and 6 and 24 hours (T↑6-24), cumulative area under the curve cTnI (CAUC24, CAUC48, and CAUC72), and cTnI≥13 ng·mL(-1) at any time point were each analyzed using univariate and multivariable Cox models to identify the probability of in-hospital and late death. Logistic EuroSCOREs and calculated creatinine clearance (CrCl) were also included. The Akaike information criterion (AIC) was used to determine goodness of fit. There were 62 of 440 deaths after a median (interquartile range) follow-up period of 7.0 (5.7 to 8.1) years. Univariate Cox analysis demonstrated T12, T24, T48, T72, T↑6-12, T↑6-24, standardized CAUC24, CAUC48, and CAUC72 each to be predictors of midterm mortality. On Cox multivariable analysis in models incorporating both logistic EuroSCOREs and CrCl, both T72 (hazard ratio [HR], 95% confidence interval [CI], 1.10 [1.06 to 1.14]; p<0.001) and CAUC72 (1.45 [1.26 to 1.62], p<0.001) were identified as independent predictors of mortality. Of these, CAUC72 was superior based on the lowest AIC. In myocardial protection studies, serial troponin I data should be collected until 72 hours postoperatively to calculate CAUC72, as this troponometric best predicts midterm mortality.
    The Annals of thoracic surgery 06/2011; 91(6):1860-7. · 3.74 Impact Factor
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    ABSTRACT: In the hypertrophied human heart, fatty acid metabolism is decreased and glucose utilisation is increased. We hypothesized that the sarcolemmal and mitochondrial proteins involved in these key metabolic pathways would mirror these changes, providing a mechanism to account for the modified metabolic flux measured in the human heart. Echocardiography was performed to assess in vivo hypertrophy and aortic valve impairment in patients with aortic stenosis (n = 18). Cardiac biopsies were obtained during valve replacement surgery, and used for western blotting to measure metabolic protein levels. Protein levels of the predominant fatty acid transporter, fatty acid translocase (FAT/CD36) correlated negatively with levels of the glucose transporters, GLUT1 and GLUT4. The decrease in FAT/CD36 was accompanied by decreases in the fatty acid binding proteins, FABPpm and H-FABP, the β-oxidation protein medium chain acyl-coenzyme A dehydrogenase, the Krebs cycle protein α-ketoglutarate dehydrogenase and the oxidative phosphorylation protein ATP synthase. FAT/CD36 and complex I of the electron transport chain were downregulated, whereas the glucose transporter GLUT4 was upregulated with increasing left ventricular mass index, a measure of cardiac hypertrophy. In conclusion, coordinated downregulation of sequential steps involved in fatty acid and oxidative metabolism occur in the human heart, accompanied by upregulation of the glucose transporters. The profile of the substrate transporters and metabolic proteins mirror the metabolic shift from fatty acid to glucose utilisation that occurs in vivo in the human heart.
    PLoS ONE 01/2011; 6(10):e26326. · 3.73 Impact Factor
  • International Journal of Surgery. 01/2011; 9(5):365-366.

Publication Stats

452 Citations
63 Downloads
2k Views
248.69 Total Impact Points

Institutions

  • 2013
    • Worldwide Clinical Trials
      Nottigham, England, United Kingdom
  • 2012–2013
    • The University of Manchester
      • Manchester Academic Health Science Centre
      Manchester, ENG, United Kingdom
    • University College London
      • Department of Primary Care and Population Health (PCPH)
      London, ENG, United Kingdom
  • 2006–2013
    • University of Birmingham
      • School of Clinical and Experimental Medicine
      Birmingham, England, United Kingdom
  • 2002–2013
    • Queen Elizabeth Hospital Birmingham
      Birmingham, England, United Kingdom
    • Imperial College London
      • Faculty of Medicine
      London, ENG, United Kingdom
  • 2006–2012
    • University Hospitals Birmingham NHS Foundation Trust
      • • Department of Cardiac Surgery
      • • Department of Cardiothoracic Surgery
      Birmingham, ENG, United Kingdom
  • 2007
    • University of Cambridge
      • Department of Medicine
      Cambridge, ENG, United Kingdom
  • 2005
    • The Queen Elizabeth Hospital
      • Department of Cardiac and Thoracic Surgery
      Tarndarnya, South Australia, Australia