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Tilburg, Netherlands

Binkhorst L.,Netherlands Cancer Institute | Binkhorst L.,Erasmus Medical Center | Bannink M.,Erasmus Medical Center | de Bruijn P.,Netherlands Cancer Institute | And 8 more authors.
Clinical Pharmacokinetics | Year: 2016

Background and Objective: The anti-oestrogen tamoxifen requires metabolic activation to endoxifen by cytochrome P450 (CYP) enzymes, predominantly CYP2D6. Potent CYP2D6-inhibiting antidepressants can seriously disrupt tamoxifen metabolism, probably influencing the efficacy of tamoxifen. For this reason, paroxetine and fluoxetine are recommended not to be used with tamoxifen in breast cancer patients. We investigated the effects of switching potent CYP2D6-inhibiting antidepressants to weak CYP2D6-inhibiting antidepressants on the plasma pharmacokinetics of tamoxifen. Methods: Ten breast cancer patients who were treated with tamoxifen in combination with a potent CYP2D6-inhibiting antidepressant (paroxetine or fluoxetine) for at least 4 weeks were enrolled. Under close supervision by a psychiatrist, patients were switched to treatment with escitalopram or venlafaxine (weak CYP2D6-inhibiting antidepressants). Before and after the switch, pharmacokinetic blood sampling was performed over 24 h. Pharmacokinetic parameters were estimated using noncompartmental analysis. Adverse effects were recorded during the study. Results: Endoxifen exposure was ~3-fold higher during escitalopram co-administration than during paroxetine or fluoxetine co-administration (median 387 nM·h [range 159–637 nM·h] versus 99.2 nM·h [range 70.0–210 nM·h]; P = 0.012; Wilcoxon signed-rank test). The ratio of endoxifen to N-desmethyltamoxifen and the ratio of 4-hydroxytamoxifen to tamoxifen increased by 3.3- and ~1.5-fold, reflecting increased CYP2D6 activity. Antidepressant switching did not result in psychiatric problems or antidepressant-related adverse effects. Conclusion: In this study, switching to the weak CYP2D6 inhibitor escitalopram was safe and feasible and resulted in clinically relevant rises in endoxifen concentrations. We therefore advise switching paroxetine and fluoxetine to escitalopram in patients using tamoxifen. However, switching should always be weighed in individual patients. © 2015, The Author(s). Source


Mans S.,Trauma Center Brabant | Reinders Folmer E.,Elisabeth TweeSteden Hospital | De Jongh M.A.C.,Trauma Center Brabant | Lansink K.W.W.,Trauma Center Brabant
Injury | Year: 2016

Introduction Several studies have suggested that severely injured patients should be transported directly to a trauma centre bypassing the nearest hospital. However, the evidence remains inconclusive. The purpose of this study was to examine the benefits in terms of mortality of direct transport to a trauma centre versus primary treatment in a level II or III centre followed by inter hospital transfer to a trauma centre for severely injured patients without Traumatic Brain Injury (TBI). Patients and methods We used the regional trauma registry and included all patients with an Injury Severity Score (ISS) >15 and an Abbreviated Injury Score <4 for head injury. We adjusted for survival bias by including "potential transfers": patients who died at the nearest hospitals before transportation to a trauma centre. Results A total of 439 patients was included. The majority of patients (349/439, 79%) was transported directly to the level I trauma centre (direct group). The transferred group was formed by the remaining 90 patients, of whom 81 were transferred to the level I trauma centre after initial stabilisation elsewhere and 9 patients died in the emergency room before transfer to a level 1 trauma centre could occur. There were no significant differences in baseline and injury characteristics between the groups. Overall, 60 patients died in-hospital including 41 of the 349 patients (12%) in the direct group and 19 of the 90 patients (21%) in the transferred group. Nine of the 19 deaths in the transferred group were ascribed to potential transfers. After adjusting for prehospital Revised Trauma Score (RTS) and ISS, the odds ratio of death was 2.40 (95%CI: 1.07-5.40) for patients in the transfer group. When potential transfer patients were excluded from the analysis, the adjusted odds ratio of death was 1.14 (95%CI: 0.43-3.01). Conclusions After adjusting for survivor bias by including potential transfers, the results of this study suggest a lower risk of death for patients who are directly transported to a level I trauma centre than for patients who receive primary treatment in a level II or III centre and are transferred to a trauma centre. However, this finding was only significant when adjusting for survival bias and therefore we conclude that it is still uncertain if there is a lower risk of death for patients who are transported directly to a level I trauma centre. © 2015 Elsevier Ltd. All rights reserved. Source


Van Der Meulen J.F.,Maxima Medical Center | Pijnenborg J.M.A.,Elisabeth TweeSteden Hospital | Boomsma C.M.,Bravis Hospital | Verberg M.F.G.,Spectrum | And 2 more authors.
BJOG: An International Journal of Obstetrics and Gynaecology | Year: 2016

Background Laparoscopic morcellation is frequently used for tissue removal after laparoscopic hysterectomy or myomectomy and may result in parasitic myomas, due to seeding of remained tissue fragments in the abdominal cavity. However, little is known about the incidence and risk factors of this phenomenon. Objectives To identify the incidence and risk factors for the development of parasitic myoma after laparoscopic morcellation. Search strategy A systematic review of the literature in Pubmed (MEDLINE) and Embase was conducted. Reference lists of identified relevant articles were checked for missing case reports. Selection criteria Studies reporting on incidence or cases of parasitic myoma diagnosed after laparoscopic morcellation were selected. Studies were excluded when history of laparoscopic morcellation was lacking or final pathology demonstrated a malignancy or endometriosis. Data collection and analysis Data were extracted and analysed on incidence of parasitic myomas and characteristics of case reports. Main results Fourty-four studies were included. Sixty-nine women diagnosed with parasitic myomas after laparoscopic morcellation were identified. Mean age was 40.8 (± 7.5) years (range 24-57), median time between surgery and diagnosis was 48.0 months (range 1-192) and mean number of parasitic myomas was 2.9 (± 3.3) (range 1-16). The overall incidence of parasitic myomas after laparoscopic morcellation was 0.12-0.95%. Conclusion Although the incidence is relatively low, it is important to discuss the risk of parasitic myoma after laparoscopic morcellation with women and balance towards alternative treatment options. The duration of steroid exposure after laparoscopic morcellation might be a risk factor for development of parasitic myomas. Tweetable abstract Systematic review on the incidence and risk factors for parasitic myoma after laparoscopic morcellation. Tweetable abstract Systematic review on the incidence and risk factors for parasitic myoma after laparoscopic morcellation. © 2015 Royal College of Obstetricians and Gynaecologists. Source


Kupper N.,University of Tilburg | Bonhof C.,University of Tilburg | Westerhuis B.,Clinical Chemical Hematology Laboratory | Widdershoven J.,Elisabeth TweeSteden Hospital | Denollet J.,University of Tilburg
Journal of Cardiac Failure | Year: 2016

Background Dyspnea is a hallmark symptom of heart failure (HF), associated with impaired functional capacity and quality of life. The experience of dyspnea is multifactorial and may originate from different sources. This study set out to examine the relative importance of potential contributors to dyspnea, ie, disease severity, inflammation and psychologic distress in a large prospective cohort of chronic HF patients. This study further aimed to examine the differential influence of cognitive and somatic symptoms of psychologic distress. Methods and Results Dyspnea complaints (Health Complaints Scale), demographic and clinical variables, and psychologic factors (ie, depression, anxiety, and Type D personality) were assessed in 464 HF patients (mean age 66.0 y, 70% men) at baseline and 1-year follow-up. Inflammatory markers (ie, tumor necrosis factor [TNF] α, interleukin [IL] 6, IL-10, soluble TNF receptors 1 and 2) were also assessed at both time points in a subsample (n = 247). Linear mixed modeling analysis with maximum likelihood estimation showed that when determinant clusters were entered separately, comorbid chronic obstructive pulmonary disease (COPD) was significantly associated with dyspnea complaints (P =.039), as were depression (P <.001) and anxiety (P <.001), whereas inflammation did not significantly affect dyspnea complaints. When all determinant clusters and covariates were entered together, results showed that body mass index (P =.013), COPD (P =.034), age (P =.005), depression (P <.001), and anxiety (P <.001) were significant independent associates of dyspnea complaints. Somatic depressive and somatic anxiety symptoms were responsible for these latter associations. Conclusions The experience and report of dyspnea in HF is determined foremost by somatic symptoms of psychologic distress, being of older age, being overweight, and having comorbid COPD, with disease severity and systemic inflammation levels playing an ancillary role. These findings suggest that psychologic distress should be considered when treating dyspnea complaints in patients with HF. © 2016 Elsevier Inc. All rights reserved. Source


Ezendam N.P.M.,University of Tilburg | Ezendam N.P.M.,Comprehensive Cancer Center the Netherlands | Pijlman B.,Robert Bosch GmbH | Bhugwandass C.,Robert Bosch GmbH | And 7 more authors.
Gynecologic Oncology | Year: 2014

Objective. his study assessed the prevalence and risk factors of chemotherapy-induced peripheral neuropathy, and its impact on health-related quality of life among ovarian cancer survivors, 2-12 years after diagnosis. Methods. Women (n = 348) diagnosed with ovarian cancer between 2000 and 2010, as registered by the Dutch population-based Eindhoven Cancer Registry, were eligible for participation. A questionnaire, including the EORTC QLQ-C30 and EORTC QLQ-OV28 measures, containing 3 items about neuropathy, was returned by 191 women (55%). Recurrence and chemotherapy data were obtained from medical records. Results. Of all 191 women, the 129 women who received chemotherapy more often reported having tingling hands/feet and feeling numbness in fingers/toes, specifically 51% reported "a little" to "very much" of these symptoms vs. about 27% who did not receive chemotherapy. Women reporting more neuropathy symptoms reported lower levels of functioning and overall quality of life. They also reported more symptoms of fatigue, nausea/vomiting, pain, dyspnea, insomnia, appetite loss, and financial problems. Moreover, women reporting more neuropathy symptoms had experienced the disease and treatment more often as being a burden and were more worried about their health, had more gastrointestinal and hormonal symptoms, hair loss and more other chemotherapy side effects. Linear regression analyses showed that more cycles of chemotherapy, more recurrences and a shorter period since last treatment were associated with a higher neuropathy score. Conclusion. Neuropathy symptoms were experienced by 51% of women with ovarian cancer who received chemotherapy even up to 12 years after the end of treatment, and this seriously affected their HRQoL. © 2014 Elsevier Inc. All rights reserved. Source

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