Marcel M C Hovens

Rijnstate Hospital, Arnheim, Gelderland, Netherlands

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Publications (25)161.46 Total impact

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    ABSTRACT: Introduction The value of diagnostic strategies in patients with clinically suspected recurrent pulmonary embolism (PE) has not been established. The aim was to determine the safety of a simple diagnostic strategy using the Wells clinical decision rule (CDR), quantitative D-dimer testing and computed tomography pulmonary angiography (CTPA) in patients with clinically suspected acute recurrent PE. Materials and Methods Multicenter clinical outcome study in 516 consecutive patients with clinically suspected acute recurrent PE without using anticoagulants. Results An unlikely clinical probability (Wells rule 4 points or less) was found in 182 of 516 patients (35%), and the combination of an unlikely CDR-score and normal D-dimer result excluded PE in 88 of 516 patients (17%), without recurrent venous thromboembolism (VTE) during 3 month follow-up (0%; 95% CI 0.0-3.4%). CTPA was performed in all other patients and confirmed recurrent PE in 172 patients (overall prevalence of PE 33%) and excluded PE in the remaining 253 patients (49%). During follow-up, seven of these 253 patients returned with recurrent VTE (2.8%; 95% CI 1.2-5.5%), of which in one was fatal (0.4 %; 95 % CI 0.02-1.9%). The diagnostic algorithm was feasible in 98% of patients. Conclusions A diagnostic algorithm consisting of a clinical decision rule, D-dimer test and CTPA is effective in the management of patients with clinically suspected acute recurrent PE. CTPA provides reasonable safety in excluding acute recurrent PE in patients with a likely clinical probability or an elevated D-dimer test for recurrent PE, with a low risk for fatal PE at follow-up.
    Thrombosis Research 01/2014; · 3.13 Impact Factor
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    ABSTRACT: Computed tomography pulmonary angiography (CTPA) is frequently requested using diagnostic algorithms for suspected pulmonary embolism (PE). For suspected deep vein thrombosis it was recently shown that doubling the D-dimer threshold in patients with low pre-test probability safely decreased the number of ultrasonographies. We evaluated the safety and efficiency of a similar strategy in patients with suspected PE. We performed a post-hoc analysis of 2213 consecutive patients of 2 cohort studies with suspected PE who were managed according to current standards: PE ruled out in case of unlikely probability (Wells rule ≤4 points) and a D-dimer level <0.5 μg/mL. CTPA was performed in all other cases. All patients were followed for three months. We calculated 3-month VTE incidence and the number of required CTPAs for selective D-dimer thresholds in patients with low clinical probability (<2 points, D-dimer threshold <1.0 μg/mL) and intermediate probability (2-6 points, D-dimer threshold <0.5 μg/mL). Using standard management, PE could be excluded without CTPA in 26% of patients, with a 3-month VTE incidence of 0.88% (95%CI 0.29-2.1%). Using selective D-dimer thresholds, PE could be excluded without CTPA in 36% of patients, with a 3-month VTE incidence of 2.1% (95%CI 1.2-3.4%) in patients managed without CTPA, an increase of 1.2 percentage points (95%CI -0.3 to 2.2). Applying selective D-dimer thresholds reduces the need for CTPA by 11 percentage points, but is associated with an increased failure rate. Prospective studies should evaluate the safety and net clinical benefit of this approach. This article is protected by copyright. All rights reserved.
    Journal of Thrombosis and Haemostasis 08/2013; · 6.08 Impact Factor
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    ABSTRACT: BACKGROUND: It is debated how patients with pulmonary embolism (PE) can be safely selected for outpatient treatment. OBJECTIVES: To compare the Hestia criteria to the European Society of Cardiology (ESC) criteria for selecting low risk patients with PE for outpatient treatment. METHODS: From 2008 to 2010, 496 patients with acute, symptomatic PE were screened and 275 were treated at home and 221 were treated in the hospital according to the Hestia Study protocol. The Hestia criteria were used to select patients for outpatient treatment. Right and left ventricular (RV, LV) diameters were measured on computed tomography images. RV dysfunction was defined as a RV/LV ratio>1.0. Patients were classified according the ESC criteria in low, intermediate and high risk groups, based on blood pressure and RV dysfunction. During 3 months follow-up adverse events were scored. RESULTS: Adverse events occurred in 22 patients (4.5%) treated in the hospital versus none of the patients treated at home (p<0.001). Sensitivity and negative predictive value for adverse outcome were 100% for the Hestia criteria and 96% and 99% for the ESC criteria, respectively. Of the patients treated at home according to the Hestia criteria, 35% were normotensive, but had RV dysfunction and were classified as intermediate risk according to the ESC criteria. No adverse events happened in these patients treated at home. CONCLUSIONS: Clinical criteria, like the Hestia criteria, could be helpful in selecting patients including those with RV dysfunction who have low risk for adverse clinical outcome and could be candidates for outpatient treatment. © 2013 International Society on Thrombosis and Haemostasis.
    Journal of Thrombosis and Haemostasis 01/2013; · 6.08 Impact Factor
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    ABSTRACT: To investigate whether an internet based, nurse led vascular risk factor management programme promoting self management on top of usual care is more effective than usual care alone in reducing vascular risk factors in patients with clinically manifest vascular disease. Prospective randomised controlled trial. Multicentre trial in secondary and tertiary healthcare setting. 330 patients with a recent clinical manifestation of atherosclerosis in the coronary, cerebral, or peripheral arteries and with at least two treatable risk factors not at goal. Personalised website with an overview and actual status of patients' risk factors and mail communication via the website with a nurse practitioner for 12 months; the intervention combined self management support, monitoring of disease control, and drug treatment. The primary endpoint was the relative change in Framingham heart risk score after 1 year. Secondary endpoints were absolute changes in the levels of risk factors and the differences between groups in the change in proportion of patients reaching treatment goals for each risk factor. Participants' mean age was 59.9 (SD 8.4) years, and most patients (n=246; 75%) were male. After 1 year, the relative change in Framingham heart risk score of the intervention group compared with the usual care group was -14% (95% confidence interval -25% to -2%). At baseline, the Framingham heart risk score was higher in the intervention group than in the usual care group (16.1 (SD 10.6) v 14.0 (10.5)), so the outcome was adjusted for the separate variables of the Framingham heart risk score and for the baseline Framingham heart risk score. This produced a relative change of -12% (-22% to -3%) in Framingham heart risk score for the intervention group compared with the usual care group adjusted for the separate variables of the score and -8% (-18% to 2%) adjusted for the baseline score. Of the individual risk factors, a difference between groups was observed in low density lipoprotein cholesterol (-0.3, -0.5 to -0.1, mmol/L) and smoking (-7.7%, -14.9% to -0.4%). Some other risk factors tended to improve (body mass index, triglycerides, systolic blood pressure, renal function) or tended to worsen (glucose concentration, albuminuria). An internet based, nurse led treatment programme on top of usual care for vascular risk factors had a small effect on lowering vascular risk and on lowering of some vascular risk factors in patients with vascular disease. Clinical trials NCT00785031.
    BMJ (online) 01/2012; 344:e3750. · 17.22 Impact Factor
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    ABSTRACT: To directly compare the performance of four clinical decision rules (CDRs) (Wells rule, revised Geneva score, simplified Wells rule and simplified revised Geneva score) in combination with D-dimer testing in excluding acute pulmonary embolism (PE). Prospective cohort study. In patients with suspected PE, the clinical probability of PE was assessed on the basis of the results of the CDRs and D-dimer test results using a computer program which calculated all CDRs and indicated the next diagnostic step. The CDRs results were compared using the outcome measure 'PE' assessed by CT-scanning or by the occurrence of venous thromboembolism or PE during a 3-month follow-up period after excluding PE. A total of 807 consecutive patients with suspected PE were included. PE prevalence was 23%. The number of patients categorised as 'PE unlikely' ranged from 62% (simplified Wells rule) to 72% (Wells rule). This CDR result combined with a normal D-dimer level excluded PE, which was the case in 22-24% of patients. There was no difference between the CDRs in the number of missed PEs (1 missed (0.5-0.6%); upper 95% CI: 2.9-3.1%). Although 30% of the patients had discordant CDR outcomes, PE was missed in none of the patients with discordant CDRs and a normal D-dimer result. All four CDRs show similar performance for exclusion of acute PE in combination with a normal D-dimer level. In addition this prospective study indicates that also the simplified scores can be used in clinical practice.
    Nederlands tijdschrift voor geneeskunde 01/2012; 156(34):A4216.
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    ABSTRACT: Several clinical decision rules (CDRs) are available to exclude acute pulmonary embolism (PE), but they have not been directly compared. To directly compare the performance of 4 CDRs (Wells rule, revised Geneva score, simplified Wells rule, and simplified revised Geneva score) in combination with d-dimer testing to exclude PE. Prospective cohort study. 7 hospitals in the Netherlands. 807 consecutive patients with suspected acute PE. The clinical probability of PE was assessed by using a computer program that calculated all CDRs and indicated the next diagnostic step. Results of the CDRs and d-dimer tests guided clinical care. Results of the CDRs were compared with the prevalence of PE identified by computed tomography or venous thromboembolism at 3-month follow-up. Prevalence of PE was 23%. The proportion of patients categorized as PE-unlikely ranged from 62% (simplified Wells rule) to 72% (Wells rule). Combined with a normal d-dimer result, the CDRs excluded PE in 22% to 24% of patients. The total failure rates of the CDR and d-dimer combinations were similar (1 failure, 0.5% to 0.6% [upper-limit 95% CI, 2.9% to 3.1%]). Even though 30% of patients had discordant CDR outcomes, PE was not detected in any patient with discordant CDRs and a normal d-dimer result. Management was based on a combination of decision rules and d-dimer testing rather than only 1 CDR combined with d-dimer testing. All 4 CDRs show similar performance for exclusion of acute PE in combination with a normal d-dimer result. This prospective validation indicates that the simplified scores may be used in clinical practice. Academic Medical Center, VU University Medical Center, Rijnstate Hospital, Leiden University Medical Center, Maastricht University Medical Center, Erasmus Medical Center, and Maasstad Hospital.
    Annals of internal medicine 06/2011; 154(11):709-18. · 13.98 Impact Factor
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    ABSTRACT: Traditionally, patients with pulmonary embolism (PE) are initially treated in the hospital with low molecular weight heparin (LMWH). The results of a few small non-randomized studies suggest that, in selected patients with proven PE, outpatient treatment is potentially feasible and safe. To evaluate the efficacy and safety of outpatient treatment according to predefined criteria in patients with acute PE. A prospective cohort study of patients with objectively proven acute PE was conducted in 12 hospitals in The Netherlands between 2008 and 2010. Patients with acute PE were triaged with the predefined criteria for eligibility for outpatient treatment, with LMWH (nadroparin) followed by vitamin K antagonists. All patients eligible for outpatient treatment were sent home either immediately or within 24 h after PE was objectively diagnosed. Outpatient treatment was evaluated with respect to recurrent venous thromboembolism (VTE), including PE or deep vein thrombosis (DVT), major hemorrhage and total mortality during 3 months of follow-up. Of 297 included patients, who all completed the follow-up, six (2.0%; 95% confidence interval [CI] 0.8-4.3) had recurrent VTE (five PE [1.7%] and one DVT [0.3%]). Three patients (1.0%, 95% CI 0.2-2.9) died during the 3 months of follow-up, none of fatal PE. Two patients had a major bleeding event, one of which was fatal intracranial bleeding (0.7%, 95% CI 0.08-2.4). Patients with PE selected for outpatient treatment with predefined criteria can be treated with anticoagulants on an outpatient basis. (Dutch Trial Register No 1319; http://www.trialregister.nl/trialreg/index.asp).
    Journal of Thrombosis and Haemostasis 06/2011; 9(8):1500-7. · 6.08 Impact Factor
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    ABSTRACT: The presence of kinase-insert domain-containing receptor (KDR) on circulating CD34+ cells is assumed to be indicative for the potential of these cells to support vascular maintenance and repair. However, in bone marrow and in granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood, less than 0.5% of CD34+ cells co-express KDR. Therefore, we studied whether CD34+/KDR+ cells are generated in the peripheral circulation. Using an ex vivo flow model, we show that activated platelets enable CD34+ cells to home to sites of vascular injury and that upon immobilization, KDR is translocated from an endosomal compartment to the cell-surface within 15 minutes. In patients with diabetes mellitus type 2, the percentage of circulating CD34+ co-expressing KDR was significantly elevated compared to age-matched controls. When treated with aspirin, the patients showed a 49% reduction in the generation of CD34+/KDR+ cells, indicating that the level of circulating CD34+/KDR+ cells also relates to in vivo platelet activation. Circulating CD34+/KDR+ are not mobilized from bone marrow as a predestined endothelial progenitor cell population but are mostly generated from circulating multipotent CD34+ cells at sites of vascular injury. Therefore, the number of circulating CD34+/KDR+ cells may serve as a marker for vascular injury.
    Arteriosclerosis Thrombosis and Vascular Biology 10/2010; 31(2):408-15. · 6.34 Impact Factor
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    ABSTRACT: Current guidelines in cardiovascular disease prevention advocate the use of carotid ultrasound measurements for risk stratification. Carotid abnormalities (plaques or increased intima-media thickness (IMT)) are associated with high risk of coronary and peripheral artery disease. An office-based measurement by clinicians would considerably broaden the clinical applicability of carotid ultrasound. In the present study we have assessed the accuracy of ultrasound detection of carotid plaques and intima-media thickness by trained internists in a routine outpatient setting. Carotid ultrasound was performed in 112 vascular outpatients by internists, after a six-week training period. The internists' results were independently compared to the reference standard, consisting of carotid ultrasound performed in a specialized vascular laboratory. Sensitivity and specificity were calculated for plaque detection and IMT determination. The mean time required to perform the scans on the outpatient department was 7.3 min (range 4.5 to 16.7 min). A high level of accuracy for detecting plaques (sensitivity 78.5%; specificity 93.6%) was achieved. Identifying abnormal IMT had lower sensitivity but adequate specificity of 46.7% and 87.6%, respectively. In conclusion, our findings demonstrate that clinicians can be trained well enough in six weeks to accurately and efficiently detect carotid plaques in an outpatient setting. IMT abnormalities were less accurately detected in the office-based approach and may require a specialized vascular laboratory.
    European Journal of Internal Medicine 02/2010; 21(1):35-9. · 2.05 Impact Factor
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    ABSTRACT: Studies have shown that aspirin may decrease blood pressure when given at bedtime but not when administered on awakening. However, until now, a biologically plausible mechanism of this striking phenomenon was not revealed. We investigated the effect of 100 mg of aspirin administered at bedtime compared with administration on awakening on plasma renin activity and aldosterone levels over 24 hours and excretion of cortisol and catecholamines in 24-hour urine samples. A randomized, placebo-controlled, double-blind, crossover trial was performed in 16 grade 1 hypertensive subjects. During 2 periods of 2 weeks separated by a 4-week washout period, participants used aspirin both at morning and at night, which was blinded with placebo. After both periods, subjects were admitted for 24 hours to measure the aforementioned parameters. Aspirin intake at bedtime compared with on awakening reduced average (24-hour) plasma renin activity by 0.08 microg/L per hour (95% CI: 0.03 to 0.13 microg/L per hour; P=0.003) without affecting aldosterone levels (95% CI: -0.01 to 0.01 nmol/L; P=0.93). Cortisol excretion in 24-hour urine was 52 nmol/24 hours (95% CI: 5 to 99 nmol/24 hours; P=0.05) lower, and dopamine and norepinephrine excretions were 0.25 micromol/24 hours (95% CI: 0.01 to 0.48 micromol/24 hours; P=0.04) and 0.22 micromol/24 hours (95% CI: -0.03 to 0.46 micromol/24 hours; P=0.02) lower in patients treated with bedtime aspirin. In conclusion, aspirin taken at bedtime compared with on awakening significantly diminished 24-hour plasma renin activity and excretion of cortisol, dopamine, and norepinephrine in 24-hour urine. Decreased activity of these pressor systems forms a biologically plausible explanation for the finding that aspirin at night may reduce blood pressure, whereas aspirin at morning does not.
    Hypertension 10/2009; 54(5):1136-42. · 6.87 Impact Factor
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    ABSTRACT: Objective.  To determine the utility of high quantitative D-dimer levels in the diagnosis of pulmonary embolism.Methods.  D-dimer testing was performed in consecutive patients with suspected pulmonary embolism. We included patients with suspected pulmonary embolism with a high risk for venous thromboembolism, i.e. hospitalized patients, patients older than 80 years, with malignancy or previous surgery. Presence of pulmonary embolism was based on a diagnostic management strategy using a clinical decision rule (CDR), D-dimer testing and computed tomography.Results.  A total of 1515 patients were included with an overall pulmonary embolism prevalence of 21%. The pulmonary embolism prevalence was strongly associated with the height of the D-dimer level, and increased fourfold with D-dimer levels greater than 4000 ng mL−1 compared to levels between 500 and 1000 ng mL−1. Patients with D-dimer levels higher than 2000 ng mL−1 and an unlikely CDR had a pulmonary embolism prevalence of 36%. This prevalence is comparable to the pulmonary embolism likely CDR group. When D-dimer levels were above 4000 ng mL−1, the observed pulmonary embolism prevalence was very high, independent of CDR score.Conclusion.  Strongly elevated D-dimer levels substantially increase the likelihood of pulmonary embolism. Whether this should translate into more intensive diagnostic and therapeutic measures in patients with high D-dimer levels irrespective of CDR remains to be studied.
    Journal of Internal Medicine 07/2008; 264(2):195 - 200. · 6.46 Impact Factor
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    ABSTRACT: Hypertension is a commonly reported side effect in antiangiogenic therapy. We investigated the hypothesis that telatinib, a small molecule angiogenesis inhibitor, impairs vascular function, induces rarefaction, and causes hypertension. A side-study was done in a phase I trial of telatinib, a small molecule tyrosine kinase inhibitor of vascular endothelial growth factor receptors 2 and 3, platelet-derived growth factor receptor, and c-KIT in patients with advanced solid tumors. Measurements of blood pressure, flow-mediated dilation, nitroglycerin-mediated dilation, aortic pulse wave velocity, skin blood flux with laser Doppler flow, and capillary density with sidestream dark field imaging were done at baseline and after 5 weeks of treatment. Blood pressure and proteinuria were measured weekly. Mean systolic and diastolic blood pressure values increased significantly at +6.6 mm Hg (P = 0.009) and +4.7 mm Hg (P = 0.016), respectively. Mean flow-mediated dilation and mean nitroglycerin-mediated dilation values significantly decreased by -2.1% (P = 0.003) and -5.1% (P = 0.001), respectively. After 5 weeks of treatment, mean pulse wave velocity significantly increased by 1.2 m/s (P = 0.001). A statistically significant reduction of mean skin blood flux of 532.8% arbitrary units was seen (P = 0.015). Capillary density statistically significantly decreased from 20.8 to 16.7 capillary loops (P = 0.015). Proteinuria developed or increased in six patients during telatinib treatment. The increase in blood pressure observed in the treatment with telatinib, an angiogenesis inhibitor, may be caused by functional or structural rarefaction.
    Clinical Cancer Research 06/2008; 14(11):3470-6. · 7.84 Impact Factor
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    ABSTRACT: Fibrin deposition at the intraluminal surface of the indwelling part of the central venous catheter (CVC) surface increases the risk of CVC-related coagulase-negative staphylococci (CoNS) infection. Therefore, repetitive enzymatic dissolution of fibrin by urokinase might reduce the risk of CVC-related infection. We undertook this study to investigate whether three times weekly urokinase rinsing of CVC reduces the incidence or severity of CVC-related infections by CoNS in patients undergoing intensive cytotoxic treatment for hematologic malignancies. In a double-blind setting, all consecutive patients with a CVC were randomly allocated to receive either urokinase rinses (5 mL of 5,000 U/mL) or placebo (saline), both three times weekly. The percentage of patients with at least one positive culture with CoNS was lower in patients receiving urokinase compared with patients receiving placebo (26% v 42%, respectively; relative risk [RR] = 0.61; 95% CI, 0.39 to 0.94). Major CVC-related CoNS infection occurred less frequently in patients receiving urokinase versus placebo (1.2% v 14.1%, respectively; RR = 0.09; 95% CI, 0.01 to 0.50). Secondary complications, including CVC-related thrombosis, were observed less frequently in the urokinase group compared with the placebo group (1.3% v 9.0%, respectively; RR = 0.14; 95% CI, 0.02 to 0.82). No severe bleeding complications attributable to urokinase were observed. Three times weekly urokinase rinsing reduces the incidence of CVC-related CoNS infection in patients treated with intensive cytotoxic therapy for hematologic malignancies, with acceptable safety.
    Journal of Clinical Oncology 02/2008; 26(3):428-33. · 18.04 Impact Factor
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    ABSTRACT: Objective. To determine the utility of high quantitative D-dimer levels in the diagnosis of pulmonary embolism. Methods. D-dimer testing was performed in consecutive patients with suspected pulmonary embolism. We included patients with suspected pulmonary embolism with a high risk for venous thromboembolism, i.e. hospitalized patients, patients older than 80 years, with malignancy or previous surgery. Presence of pulmonary embolism was based on a diagnostic management strategy using a clinical decision rule (CDR), D-dimer testing and computed tomography. Results. A total of 1515 patients were included with an overall pulmonary embolism prevalence of 21%. The pulmonary embolism prevalence was strongly associated with the height of the D-dimer level, and increased fourfold with D-dimer levels greater than 4000 ng mL(-1) compared to levels between 500 and 1000 ng mL(-1). Patients with D-dimer levels higher than 2000 ng mL(-1) and an unlikely CDR had a pulmonary embolism prevalence of 36%. This prevalence is comparable to the pulmonary embolism likely CDR group. When D-dimer levels were above 4000 ng mL(-1), the observed pulmonary embolism prevalence was very high, independent of CDR score. Conclusion. Strongly elevated D-dimer levels substantially increase the likelihood of pulmonary embolism. Whether this should translate into more intensive diagnostic and therapeutic measures in patients with high D-dimer levels irrespective of CDR remains to be studied.
    Journal of Internal Medicine 01/2008; · 6.46 Impact Factor
  • Archives of Internal Medicine - ARCH INTERN MED. 01/2008; 168(5):550-550.
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    ABSTRACT: Low-grade inflammation plays a pivotal role in atherogenesis in type 2 diabetes. Next to its antithrombotic effects, several lines of evidence demonstrate anti-inflammatory properties of aspirin. We determined the effects of aspirin on inflammation - represented by C-reactive protein (CRP) and interleukin-6 (IL-6) - in type 2 diabetic subjects without cardiovascular disease and assessed differential effects of aspirin 300 mg compared with 100 mg. A randomized, placebo-controlled, double-blind, crossover trial was performed in 40 type 2 diabetic patients. In two periods of 6 weeks, patients used 100 or 300 mg aspirin and placebo. Plasma CRP and IL-6 levels were measured before and after both periods. Use of aspirin resulted in a CRP reduction of 1.23 +/- 1.02 mg/l (mean +/- s.e.m.), whereas use of placebo resulted in a mean increase of 0.04 +/- 1.32 mg/l (P = 0.366). Aspirin reduced IL-6 with 0.7 +/- 0.5 pg/ml, whereas use of placebo resulted in a mean increase of 0.2 +/- 0.8 pg/ml (P = 0.302). There were no significant differences in effects on CRP and IL-6 between 100 and 300 mg aspirin. Our results indicate that a 6-week course of aspirin does not improve low-grade inflammation in patients with type 2 diabetes without cardiovascular disease, although a modest effect could not be excluded. No significant differential effects between aspirin 100 and 300 mg were found.
    Diabetes Obesity and Metabolism 12/2007; 10(8):668-74. · 5.18 Impact Factor
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    ABSTRACT: We describe 2 renal transplant recipients with severe but reversible neurological manifestations related to Varicella zoster virus (VZV) cerebral vasculopathy. To the best of our knowledge, this is the first description of cerebral VZV vasculopathy in solid organ transplant recipients. We review the published literature on the clinical presentation, diagnosis and treatment. In solid organ transplant recipients presenting with neurological signs and symptoms, a diagnosis of VZV-associated vasculopathy should be considered.
    Transplant Infectious Disease 10/2007; 9(3):237-40. · 1.98 Impact Factor
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    ABSTRACT: Despite clopidogrel therapy, patients undergoing percutaneous coronary intervention (PCI) with stenting are at risk of recurrent coronary events. This could be partly explained by a reduced efficacy of clopidogrel to inhibit platelet aggregation, an ex vivo defined phenomenon called clopidogrel nonresponsiveness or resistance. However, both prevalence and associated cardiovascular risks remain unclear. We systematically reviewed evidence on prevalence and clinical consequences of laboratory clopidogrel nonresponsiveness in patients undergoing PCI. Using predefined strategies, we searched electronic databases. To be included, articles should report on PCI patients treated with clopidogrel, contain a clear description of the method used to establish the effects of clopidogrel, and report the prevalence of clopidogrel nonresponsiveness or incidence of cardiovascular events. We analyzed prevalences with a linear mixed model that accounts for study covariates and we pooled odds ratios of clinical consequences with a random-effects model. We identified 25 eligible studies that included a total of 3688 patients. Mean prevalence of clopidogrel nonresponsiveness was 21% (95% CI, 17%-25%) and was inversely correlated with time between clopidogrel loading and determination of nonresponsiveness and used loading dose. The pooled odds ratio of cardiovascular outcome was 8.0 (95% CI, 3.4-19.0). Laboratory clopidogrel nonresponsiveness can be found in approximately 1 in 5 patients undergoing PCI. Patients ex vivo labeled nonresponsive are likely to be also "clinically nonresponsive," as they exhibit increased risks of worsened cardiovascular outcomes. Our results indicate that use of a 600-mg clopidogrel loading dose will reduce these risks, which needs to be confirmed in large prospective studies.
    American heart journal 09/2007; 154(2):221-31. · 4.65 Impact Factor
  • Journal of Thrombosis and Haemostasis 08/2007; 5(7):1562-4. · 6.08 Impact Factor
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    ABSTRACT: The absolute risk of recurrences among patients using aspirin for prevention of cardiovascular events remains high. Persistent platelet reactivity despite aspirin therapy might explain this in part. Reported prevalences of this so-called aspirin resistance vary widely, between 0% and 57%. The aim of the study was to systematically review all available evidence on prevalence of aspirin resistance and to study determinants of reported prevalence. Using a predefined search strategy, we searched electronic databases MEDLINE, EMBASE, CENTRAL, and Web of Science. To be included in our analysis, articles had to contain a laboratory definition of aspirin resistance, use aspirin as secondary prevention, and report associated prevalence. We included 34 full-text articles and 8 meeting abstracts. The mean prevalence of aspirin resistance was 24% (95% CI 20%-28%). After adjustment for differences in definition, used dosage, and population, a statistically significant higher prevalence was found in studies with aspirin dosage < or =100 mg compared with > or =300 mg (36% [95% CI 28%-43%] vs 19% [95% CI 11%-26%], P < .0001). Studies measuring platelet aggregation using light aggregometry with arachidonic acid as an agonist had a pooled unadjusted prevalence of 6% (95% CI 0%-12%). In studies using point-of-care platelet function-analyzing devices, the unadjusted prevalence was significantly higher, at 26% (95% CI 21%-31%). Prevalences widely differ between studies reporting on aspirin resistance. Both aspirin dosage and the method of defining aspirin resistance strongly influence estimated prevalence, which explains found heterogeneity among studies. On average, it appears that about 1 in 4 individuals may express biochemically defined aspirin resistance.
    American heart journal 03/2007; 153(2):175-81. · 4.65 Impact Factor

Publication Stats

845 Citations
161.46 Total Impact Points

Institutions

  • 2011–2014
    • Rijnstate Hospital
      Arnheim, Gelderland, Netherlands
  • 2005–2012
    • Leiden University Medical Centre
      • • Department of Endocrinology and General Internal Medicine
      • • Department of Clinical Epidemiology
      Leyden, South Holland, Netherlands
  • 2003
    • Amphia Ziekenhuis
      Breda, North Brabant, Netherlands