http://repub.eur.nl/res/aut/36660/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/31953/ 2012-01-01T00:00:00Z Summary. Background: Hemophilia A patients have a lower cardiovascular mortality rate than the general population. Whether this protection is caused by hypocoagulability or decreased atherogenesis is unclear. Objectives: To evaluate atherosclerosis and endothelial function in hemophilia A patients with and without obesity as well as in matched, unaffected controls. Methods: Fifty-one obese (body mass index [BMI]≥30kgm-2) and 47 non-obese (BMI≤25kgm-2) hemophilia A patients, and 42 obese and 50 matched non-obese male controls were included. Carotid and femoral intima-media thickness [IMT] and brachial flow-mediated dilatation (FMD) were measured as markers of atherogenesis and endothelial function. Results: The overall population age was 50±13 years. Carotid IMT was increased in obese subjects (0.77±0.22mm) as compared with non-obese subjects (0.69±0.16mm) [mean difference 0.07mm (95% confidence interval [CI] 0.02-0.13, P=0.008)]. No differences in mean carotid and femoral IMT between obese hemophilic patients and obese controls were found (mean difference of 0.02mm [95% CI -0.07-0.11, P=0.67], and mean difference of 0.06mm [95% CI -0.13-0.25, P=0.55], respectively). Thirty-five per cent of the obese hemophilic patients and 29% of the obese controls had an atherosclerotic plaque (P=0.49), irrespective of the severity of hemophilia. Brachial FMD was comparable between obese hemophilic patients and obese controls (4.84%±3.24% and 5.32%±2.37%, P=0.45). Conclusion: Hemophilia A patients with obesity develop atherosclerosis to a similar extent as the general male population. Detection and treatment of cardiovascular risk factors in hemophilic patients is equally necessary. http://repub.eur.nl/res/pub/33214/ 2011-11-01T00:00:00Z Context: Venous thrombosis has frequently been reported in patients with endogenous Cushing's syndrome (CS). Objective: The aim of this study was to evaluate the incidence of venous thromboembolism (VTE) in patients with CS prior to treatment and after surgery. Design and Setting: We conducted a multicenter cohort study at all university medical centers in The Netherlands. Patients: Consecutive patients diagnosed withendogenousCS of benign originbetweenJanuary 1990 and June 2010 were eligible for inclusion. Patients surgically treated for nonfunctioning pituitary adenoma served as controls for the incidence of postoperative VTE in ACTH-dependent CS. Main Outcome Measures: We documented all objectively confirmed VTE during 3 yr prior to, and 3 yr after treatment onset. The incidences of VTE were expressed as incidence rates. Results: A total of 473 patients (mean age 42 yr, 363 women) were included (360 ACTH-dependent pituitary CS). The total number of person-years was 2526. Thirty-seven patients experienced VTE during the study period, resulting in an incidence rate of 14.6 [95% confidence interval (CI) 10.3-20.1] per 1000 person-years. The incidence rate for first-ever VTE prior to treatment was 12.9 (95% CI 7.5-12.6) per 1000 person-years (17 events). The risk of postoperative VTE, defined as risk within 3 months after surgery, was 0% for ACTH-independent and 3.4% (95% CI 2.0 -5.9) for ACTHdependent CS (12 events in 350 patients); most events occurred between 1 wk and 2 months after surgery. Compared with the controls, the risk of postoperative VTE in patients undergoing transsphenoidal surgery was significantly greater (P = 0.01). Conclusions: Patients with CS are at high risk of VTE, especially during active disease and after pituitary surgery. Guidelines on thromboprophylaxis are urgently needed. Copyright http://repub.eur.nl/res/pub/26671/ 2011-07-01T00:00:00Z http://repub.eur.nl/res/pub/33108/ 2008-01-01T00:00:00Z The Wells rule is a widely applied clinical decision rule in the diagnostic work-up of patients with suspected pulmonary embolism (PE).The objective of this study was to replicate, validate and possibly simplify this rule.We used data collected in 3,306 consecutive patients with clinically suspected PE to recalculate the odds ratios for the variables in the rule, to calculate the proportion of patients with PE in the probability categories,the area under the ROC curve and the incidence of venous thromboembolism during follow-up. We compared these measures with those for a modified and a simplified version of the decision rule. In the replication, the odds ratios in the logistic regression model were found to be lower for each of the seven individual variables (p=0.02) but the proportion of patients with PE in the probability categories in our study group were comparable to those in the original derivation and validation groups.The area under the ROC of the original, modified and simplified decision rule was similar: 0.74 (p=0.99; p=0.07).The venous thromboembolism incidence at three months in the group of patients with a Wells score ≤ 4 and a normal D-climer was 0.5%, versus 0.3% with a modified rule and 0.5% with a simplified rule.The proportion of patients safely excluded for PE was 32%, versus 31 % and 30%, respectively.This study further validates the diagnostic utility of the Wells rule and indicates that the scoring system can be simplified to one point for each variable.