Peter Mills

National Heart, Lung, and Blood Institute, Maryland, United States

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Publications (23)106.87 Total impact

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    ABSTRACT: Aim: This study presents an interim safety and feasibility analysis of the REGENERATE-IHD randomized controlled trial, which is examining the safety and efficacy of three different delivery routes of bone marrow-derived stem cells (BMSCs) in patients with ischemic heart failure. Methods & results: The first 58 patients recruited to the REGENERATE-IHD study are included in this interim analysis (pilot). Symptomatic patients with ischemic heart failure were randomized to receive subcutaneous granulocyte colony-stimulating factor or saline injections only; or subcutaneous granulocyte colony-stimulating factor injections followed by intracoronary or intramyocardial injections of BMSCs or serum (control). No significant differences were found in terms of safety and feasibility between the different delivery routes, with no significant difference in procedural complications or major adverse cardiac events. There was a signal towards improved heart failure symptoms in the patients treated with intramyocardial injection of mobilized BMSCs. Conclusion: Peripheral mobilization of BMSCs with or without subsequent direct myocardial delivery appears safe and feasible in patients with chronic ischemic heart failure.
    Regenerative medicine. 05/2014; 9(3):269-78.
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    ABSTRACT: Acute myocardial infarction (AMI) remains a major cause of mortality and morbidity worldwide despite the latest therapeutic advances designed to decrease myocardial injury. Preclinical and emerging clinical evidence show that the intracoronary injection of autologous bone marrow mononuclear cells (BMCs) following AMI leads to improvement in left ventricular ejection function (LVEF). In this clinical trial we will for the first time assess the effect of early (<24 h) infusion of autologous BMCs following AMI on cardiac function. REGENERATE-AMI is a double-blind, randomised, multicentre, placebo-controlled trial to determine whether early (<24 h) intracoronary infusion of BMCs improves LVEF after AMI. The study will enrol 100 patients presenting with an anterior AMI demonstrating anterior regional wall motion abnormality. Patients will be randomised to receive intracoronary infusion of BMCs or placebo (0.9% saline). Primary endpoint will be change in LVEF at 1 year compared to baseline, measured by cardiac MRI. Secondary endpoints at 6 months include the change in global LVEF relative to baseline measured by quantitative left ventriculography and echocardiography, as well as major adverse cardiac events which is also measured at 1 year. The study will be performed in agreement with the Declaration of Helsinki and is approved by local ethics committee (NRES Committee London West London: 07/Q0603/76). http://clincialtrials.gov (NCT00765453). The results of the trial will be published according to the CONSORT statement and will be presented at conferences and reported in peer-reviewed journals.
    BMJ Open 01/2014; 4(2):e004258. · 2.06 Impact Factor
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    ABSTRACT: Background: The incidence of infective endocarditis (IE) in dialysis patients is higher than the general population. Dialysis patients who develop endocarditis are thought to have a poorer prognosis than other patients with IE. Aim: To examine the risk profiles, clinical features, and outcomes of patients on dialysis who developed IE in a large cohort. Design and Methods: A retrospective analysis of all patients developing IE on dialysis (using the modified Duke criteria) was undertaken between 1998 and 2011. Patients were identified from a prospectively collected clinical database. Results: 42 patients developed IE out of a total incident dialysis population of 1,500 over 13 years. 95% of the patients (40/42) were on long-term haemodialysis (HD) and 5% (2/42) on peritoneal dialysis. Mean patient age was 55.2 years (IQR: 43-69), and mean duration of HD prior to IE was 57.4 months. Primary HD access at the time of diagnosis was an arteriovenous fistula in 35% (14/40), a dual-lumen tunnelled catheter in 55% (22/40), and a dual-lumen non-tunnelled catheter in 10% (4/40). Staphylococcus aureus (including methicillin-resistant S. aureus) was present in 57.1% (24/42). The aortic valve was affected in 42.8% of the patients (18/42), the mitral valve in 30.9% (13/42), and both valves in 9.5% (4/42). 33.3% of the patients had an abnormal valve before the episode of IE. In 21.4% (9/42), valve surgery was performed and mortality was lower in the surgical group compared to the group managed medically during hospitalisation (11.1 vs. 15.2%, p = 0.892), at 3 months (13.1 vs. 19.6%, p = 0.501), and during follow-up (p = 0.207), but this difference did not reach statistical significance. Age >60 years, septic emboli, and methicillin-resistant S. aureus were all adverse prognostic factors. Patients receiving surgery were younger (mean 47.1 ± 14.4 years vs. 57.4 ± 14.3, p = 0.049) and less likely to be infected with S. aureus (surgery 33.3% vs. antibiotics 63.6%, p = 0.046). Conclusion: This is one of the largest reported series of IE in dialysis patients. The incidence of IE remains high and the prognosis poor in dialysis patients, although patients selected for early valve surgery have good 1-year survival.
    Nephron Clinical Practice 07/2013; 123(3-4):151-156. · 1.65 Impact Factor
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    ABSTRACT: AIMS: Myocardial revascularization by either coronary artery bypass graft surgery (CABG) or percutaneous coronary intervention (PCI) carries the risk of serious complications. Observational data suggest that outcomes may be improved by experienced operators, but there are few studies that have analysed the relationship between mortality and primary operator grade. The aim of this study was to investigate the effect of operator grade (trainee vs. consultant) upon outcomes of revascularization procedures. METHODS AND RESULTS: This was an observational study at a tertiary cardiology centre with accredited training programmes, between 2003 and 2011. A total of 22 697 consecutive patients undergoing either CABG or PCI were included. Associations between operator grade and mortality were assessed by hazard ratios, estimated by Cox regression analyses; 6689 patients underwent CABG, whereas 16 008 underwent PCI. Trainees performed 1968 (29.4%) CABG procedures and 8502 (53.1%) PCI procedures. The proportion of procedures performed by trainees declined over time for both CABG (30.2% in 2003 vs. 26.0% in 2010) and for PCI (58.1% in 2003 vs. 44.5% in 2010). In the unadjusted Cox analysis, consultant operator grade was associated with an increased 5-year mortality after both CABG [HR: 1.26 (95% CI: 1.07-1.47)] and PCI procedures [HR: 1.34 (95% CI: 1.22-1.47)] compared with a trainee operator. However, following multiple adjustment, consultant grade was no longer associated with mortality after either procedure [CABG: HR: 1.02 (95% CI: 0.87-1.20), PCI: HR: 1.08 (95% CI: 0.98-1.20)]. CONCLUSION: There was no observed detrimental effect on patient outcomes arising from procedures undertaken by trainees working in a structured training environment compared with consultants.
    European Heart Journal 05/2013; · 14.72 Impact Factor
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    ABSTRACT: Constrictive pericarditis (CP) is a recognised, but unusual cause of chronic ascites.1 ,2 Patients with pericardial constriction may present to non-cardiological specialties,3 ,4 with the symptoms and signs leading to the diagnosis of congestive cardiac failure, lung disease or liver disease.5 ,6 It is important to suspect and rule out CP because with surgery it is treatable and potentially curable. Much of the difficulty in diagnosing CP can be attributed to its insidious course and the absence of typical cardiopulmonary symptoms. Over 50% of patients ending up with pericardiectomy lack symptoms of dyspnoea and orthopnoea.7 We present two cases, which highlight the potential difficulties in diagnosing CP in patients with chronic ascites. We review the key steps in diagnosis and management, emphasising that raised jugular venous pressure (JVP) is one of the crucial observations in making the diagnosis.
    Frontline Gastroenterology. 01/2012; 3(4):233-237.
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    ABSTRACT: To compare short and medium-term prognosis in South Asian and Caucasian patients undergoing percutaneous coronary intervention (PCI) to determine if there are ethnic differences in case death rates. Retrospective cohort study. A cardiology referral centre in east London. 9771 patients who underwent PCI from October 2003 to December 2007 of whom 7966 (81.5%) were Caucasian and 1805 (18.5%) were South Asian. In-hospital major adverse cardiac events (MACE; death, myocardial infarction, stroke and target vessel revascularisation), subsequent revascularisation rates (PCI and coronary artery bypass grafting; CABG) and all-cause mortality during a median follow-up of 2.5 years (range 1.5-3.6 years). South Asian patients were younger than Caucasian patients (59.69±0.27 vs 64.69±0.13 years, p<0.0001), and more burdened by cardiovascular risk factors, particularly type II diabetes mellitus (45.9%±1.2% vs 15.7%±0.4%, p<0.0001). The in-hospital rates of MACE were similar for South Asians and Caucasians (3.5% vs 2.8%, p=0.40). South Asians had higher rates of clinically driven PCI for restenosis and subsequent CABG, although Kaplan-Meier estimates of all-cause mortality showed no significant differences; this was regardless of whether PCI was performed post-acute coronary syndrome or as an elective procedure. The adjusted hazard of death for South Asians compared with Caucasians was 1.00 (95% CI 0.81 to 1.23). In this large PCI cohort, the in-hospital and longer-term mortality of South Asians appeared no worse than that of Caucasians. South Asians had higher rates of restenosis and CABG during follow-up. Data suggest that the excess coronary mortality for South Asians compared with Caucasians is not explained by differences in case-fatality rates.
    Heart (British Cardiac Society) 11/2011; 98(5):414-9. · 5.01 Impact Factor
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    ABSTRACT: In patients presenting with acute cardiac symptoms, abnormal ECG and raised troponin, myocarditis may be suspected after normal angiography. To analyse cardiac magnetic resonance (CMR) findings in patients with a provisional diagnosis of acute coronary syndrome (ACS) in whom acute myocarditis was subsequently considered more likely. 79 patients referred for CMR following an admission with presumed ACS and raised serum troponin in whom no culprit lesion was detected were studied. 13% had unrecognised myocardial infarction and 6% takotsubo cardiomyopathy. The remainder (81%) were diagnosed with myocarditis. Mean age was 45±15 years and 70% were male. Left ventricular ejection fraction (EF) was 58±10%; myocardial oedema was detected in 58%. A myocarditic pattern of late gadolinium enhancement (LGE) was detected in 92%. Abnormalities were detected more frequently in scans performed within 2 weeks of symptom onset: oedema in 81% vs 11% (p<0.0005), and LGE in 100% vs 76% (p<0.005). In 20 patients with both an acute (<2 weeks) and convalescent scan (>3 weeks), oedema decreased from 84% to 39% (p<0.01) and LGE from 5.6 to 3.0 segments (p=0.005). Three patients presented with sustained ventricular tachycardia, another died suddenly 4 days after admission and one resuscitated 7 weeks following presentation. All 5 patients had preserved EF. Our study emphasises the importance of access to CMR for heart attack centres. If myocarditis is suspected, CMR scanning should be performed within 14 days. Myocarditis should not be regarded as benign, even when EF is preserved.
    Heart (British Cardiac Society) 11/2010; 97(16):1312-8. · 5.01 Impact Factor
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    Journal of Cardiovascular Magnetic Resonance 01/2010; · 4.44 Impact Factor
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    Journal of Cardiovascular Magnetic Resonance 01/2010; · 4.44 Impact Factor
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    ABSTRACT: To evaluate the reliability and feasibility of assessing the performance of medical specialist registrars (SpRs) using three methods: the mini-clinical evaluation exercise (mini-CEX), directly observed procedural skills (DOPS) and multi-source feedback (MSF) to help inform annual decisions about the outcome of SpR training. We conducted a feasibility study and generalisability analysis based on the application of these assessment methods and the resulting data. A total of 230 SpRs (from 17 specialties) in 58 UK hospitals took part from 2003 to 2004. Main outcome measures included: time taken for each assessment, and variance component analysis of mean scores and derivation of 95% confidence intervals for individual doctors' scores based on the standard error of measurement. Responses to direct questions on questionnaires were analysed, as were the themes emerging from open-comment responses. The methods can provide reliable scores with appropriate sampling. In our sample, all trainees who completed the number of assessments recommended by the Royal Colleges of Physicians had scores that were 95% certain to be better than unsatisfactory. The mean time taken to complete the mini-CEX (including feedback) was 25 minutes. The DOPS required the duration of the procedure being assessed plus an additional third of this time for feedback. The mean time required for each rater to complete his or her MSF form was 6 minutes. This is the first attempt to evaluate the use of comprehensive workplace assessment across the medical specialties in the UK. The methods are feasible to conduct and can make reliable distinctions between doctors' performances. With adaptation, they may be appropriate for assessing the workplace performance of other grades and specialties of doctor. This may be helpful in informing foundation assessment.
    Medical Education 05/2008; 42(4):364-73. · 3.55 Impact Factor
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    Andrew Wragg, Peter Mills, Roger Hall
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    ABSTRACT: A 70 year old man presented with microscopic haematuria and proteinuria and a fever five months after having a transurethral resection of the prostate (TURP). Initially urological review was arranged as the family doctor thought that a urinary infection was the most likely diagnosis. The patient was concerned that he was not getting better and he self-referred to a physician. He had continuing fever, weight loss, and malaise. The physician detected a mitral pan-systolic murmur that had not been heard before. On the basis of this finding infective endocarditis was suspected and investigations begun. His subsequent course and its management are discussed in an interactive case presentation.
    Heart (British Cardiac Society) 06/2004; 90(5):580. · 5.01 Impact Factor
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    Andrew Wragg, Peter Mills, Roger Hall
    Heart. 01/2004; 90(5):580-580.
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    Heart (British Cardiac Society) 11/2003; 89(10):1253-4. · 5.01 Impact Factor
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    ABSTRACT: To analyse differences in the presentation and management of Bangladeshi and white patients with Q wave acute myocardial infarction (AMI). Prospective observational study. East London teaching hospital. 263 white and 108 Bangladeshi patients admitted with Q wave AMI. Character of presenting symptoms, their interpretation by the patient, and the provision of emergency treatment. There were no significant differences between Bangladeshi and white patients in the time from pain onset to hospital arrival (arrival time 64.5 (117.5) minutes v 63.0 (140.3) minutes, p = 0.63), but once in hospital it took almost twice as long for Bangladeshi as for white patients to receive thrombolysis (median (interquartile range) door to needle time 42.5 (78.0) minutes v 26.0 (47.7) minutes, p = 0.012). Bangladeshis were significantly less likely than whites to complain of central chest pain (odds ratio (OR) 0.11, 95% confidence interval (CI) 0.03 to 0.38; p = 0.0006) or to offer classic descriptions of the character of the pain (OR 0.25, 95% CI 0.09 to 0.74; p = 0.0118). These differences persisted after adjustment for age, sex, and risk factor profile differences including diabetes. Proportions of Bangladeshi and whites interpreting their symptoms as "heart attack" were similar (45.2% v 46.9%; p = 0.99). Bangladeshi patients with AMI often present with atypical symptoms, which may lead to slower triage in the casualty department and delay in essential treatment. This needs recognition by emergency staff if mortality rates in this high risk group are to be reduced.
    Heart (British Cardiac Society) 04/2003; 89(3):276-9. · 5.01 Impact Factor
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    ABSTRACT: Assessing the performance of doctors while they are engaged in clinical work is a challenging concept. The introduction of objective-based curricula provides the stimulus and opportunity for the Royal Colleges of Physicians to develop relevant and reliable methods of in-service assessment. We propose to pilot a study investigating the validity, reliability and feasibility of three assessment methods--direct observation of the clinical encounter using an adapted mini-CEX, direct observation of the performance of practical procedures (DOPS), and the doctor's ability to perform effectively as part of a team using 360 degree assessment. The methods will be studied in the setting of routine clinical care. Whilst demanding of time from both trainees and trainers, they will represent a significant advance on the current system which is characterised by a lack of evidence in the assessment process.
    Clinical medicine (London, England) 03/2003; 3(2):131-4. · 1.32 Impact Factor
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    Peter Mills, Roger Hall
    01/2003;
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    ABSTRACT: To determine the incremental value of clinical data, troponin T, ST segment monitoring, and heart rate variability for predicting outcome in patients with non-ST elevation acute coronary syndromes. Prospective cohort study of 304 consecutive patients. Baseline clinical and electrocardiographic data were recorded, serial blood samples were obtained for troponin T assay, and 48 hour Holter monitoring was performed for ST segment and heart rate variability analysis. End points were cardiac death and non-fatal myocardial infarction during 12 months' follow up. After 12 months, 7 patients had died and 21 had had non-fatal myocardial infarction. The risk of an event was increased by troponin T > 0.1 microg/l, T wave inversion on the presenting ECG, Holter ST shift, and a decrease in the standard deviation of 5 minute mean RR intervals. Positive predictive values of individual multivariate risk were low; however, analysis of all multivariate risk markers permitted calculation of a cumulative risk score, which increased the positive predictive value to 46.9% while retaining a negative predictive value of 96.9%. A cumulative approach to risk stratification in non-ST elevation coronary syndromes successfully identifies a group in whom the risk of cardiac death or non-fatal myocardial infarction approaches 50%.
    Heart (British Cardiac Society) 01/2003; 89(1):36-41. · 5.01 Impact Factor
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    ABSTRACT: Vitamin-D deficiency and vitamin-D receptor genotype (VDR) are risk factors for several disorders with inflammatory components, including coronary heart disease (CHD) and diabetes, though the mechanisms involved are unclear. Aim: To examine the hypothesis that vitamin D status modulates the matrix metalloproteinase (MMP) system in a population with a high prevalence of vitamin D deficiency, a situation affecting susceptibility to CHD and diabetes. Prospective cross-sectional, interventional and embedded studies. Circulating MMP2,9, the inhibitor TIMP-1 and C-reactive protein (CRP) were measured during studies of vitamin-D deficiency as a risk factor for type 2 diabetes and CHD in 171 healthy British Bangladeshi adults, free of known diabetes or major illness. Vitamin D status, VDR genotype, body-build, blood pressure, lipid and insulin profiles, glucose tolerance, fibrinogen, PAI-1, folate and homocysteine were measured. Vitamin-D-deficient subjects were re-assessed after 1 years' supplementation. MMP, TIMP-1 and CRP levels were measured in 41 subjects halfway through 5-year follow-up. Independent determinants of circulating concentrations of MMP9, TIMP-1 and CRP were assessed by multiple regression analysis. Vitamin D status was the sole determinant of circulating MMP9 (inversely) and an independent determinant of CRP (inversely). Determinants of TIMP-1 were MMP9, systolic blood-pressure (directly) and VDR genotype (TaqI). Significant reductions in MMP9 (-68%), TIMP-1 (-38%) and CRP (-23%) concentrations followed vitamin-D supplementation. Vitamin-D insufficiency is associated with increased circulating MMP2,9 and CRP, correctable by supplementation. This finding provides a possible mechanism for tissue damage in chronic inflammatory conditions, including CHD and diabetes.
    QJM: monthly journal of the Association of Physicians 01/2003; 95(12):787-96. · 2.36 Impact Factor
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    ABSTRACT: The goal of this study was to determine the interaction between smoking and the glycoprotein IIIa P1(A2) polymorphism in patients admitted with non-ST-elevation acute coronary syndromes (ACS). An increased incidence of the P1(A2) polymorphism in smokers presenting with ST-elevation acute myocardial infarction (AMI) has recently been reported. We, therefore, postulated that, as a consequence of this interaction, fewer smokers with the P1(A2) polymorphism would present with non-ST-elevation ACS. We performed a prospective cohort analysis of 220 white Caucasoid patients admitted with non-ST-elevation ACS fulfilling Braunwald class IIIb criteria for unstable angina who were stratified by smoking status. There were twice as many nonsmokers as smokers. Nonsmokers compared with smokers were older (mean [SD]; 63.9 [11.2] vs. 57.6 [10.3]; p < 0.0001), more likely to have had a previous admission with unstable angina (24.3% vs. 13.2%; p = 0.051) and AMI (45.8% vs. 30.3%; p < 0.026), more likely to have undergone revascularization (24.3% vs. 1.8%; p = 0.028) and were more likely to be on aspirin on admission (60.4% vs. 44.7%; p = 0.026). The proportion of nonsmokers positive for the P1(A2) polymorphism was equivalent to that expected for this population but was significantly reduced in smokers (28.7% vs. 10%; Pearson chi-square = 9.09, p = 0.0026). In a logistic regression model, the odds ratio (OR) for being positive for the P1(A2) polymorphism was significantly reduced by smoking (OR [interquartile range]: 0.26 [0.11 to 0.62]; p = 0.0026). There is a significant reduction in the P1(A2) polymorphism in smokers admitted with non-ST-elevation ACS compared with nonsmokers, which suggests an interaction between smoking and this polymorphism.
    Journal of the American College of Cardiology 12/2001; 38(6):1639-43. · 14.09 Impact Factor
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    ABSTRACT: This study was done to determine the effects of angiotensin-converting enzyme (ACE) inhibition and other clinical factors on troponin release in non-ST-elevation acute coronary syndrome (ACS). Troponin is now widely used as a marker of risk in ACS, but determinants of its release have not been defined. This was a prospective cohort study of 301 consecutive patients admitted with non-ST-elevation ACS. Baseline clinical data were recorded, ACE gene polymorphism was determined and serial blood samples were obtained for troponin-I assay. Significant troponin-I release (>0.1 microg/l) was detected in 93 (31%) patients. Pretreatment with ACE inhibitors, recorded in 53 patients (17.6%), independently reduced the odds of troponin-I release (odds ratio 0.25; 95% confidence intervals 0.10 to 0.64) and was associated with lower maximum troponin-I concentrations (median [interquartile range]) compared with patients not pretreated with ACE inhibitors (0.44 microg/l [0.19 to 2.65 microg/l] vs. 4.18 microg/l [0.91 to 12.41 microg/l], p = 0.01). Pretreatment with aspirin, recorded in 173 patients (57.5%), did not significantly reduce the odds of troponin-I release after adjustment but was associated with lower maximum troponin-I concentrations compared with patients not pretreated with aspirin (2.31 microg/l [0.72 to 8.02 microg/l] vs. 5.85 microg/l [1.19 to 12.79 microg/l], p = 0.05). The ACE genotyping (n = 268) showed 81 patients (30%) DD homozygous and 77 (29%) II homozygous. There was no association between ACE genotype and troponin release. We conclude that ACE inhibition reduces troponin release in non-ST-elevation ACS. This is likely to be mediated by the beneficial effects of treatment on vascular reactivity and the coagulation system.
    Journal of the American College of Cardiology 10/2001; 38(3):724-8. · 14.09 Impact Factor

Publication Stats

446 Citations
106.87 Total Impact Points

Institutions

  • 2004
    • National Heart, Lung, and Blood Institute
      Maryland, United States
  • 2003
    • Royal College of Physicians
      Londinium, England, United Kingdom
    • Queen Mary, University of London
      Londinium, England, United Kingdom
  • 2001
    • University of London
      Londinium, England, United Kingdom