Erasmus MCSophia Childrens Hospital

Rotterdam, Netherlands

Erasmus MCSophia Childrens Hospital

Rotterdam, Netherlands
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Berghmans J.M.,Queen Paola Childrens Hospital | Berghmans J.M.,Erasmus MCSophia Childrens Hospital | Poley M.J.,Erasmus University Rotterdam | Poley M.J.,Erasmus MCSophia Childrens Hospital | And 9 more authors.
Paediatric Anaesthesia | Year: 2017

Background: The modified Yale Preoperative Anxiety Scale is widely used to assess children's anxiety during induction of anesthesia, but requires training and its administration is time-consuming. A Visual Analog Scale, in contrast, requires no training, is easy-to-use and quickly completed. Aim: The aim of this study was to evaluate a Visual Analog Scale as a tool to assess anxiety during induction of anesthesia and to determine cut-offs to distinguish between anxious and nonanxious children. Methods: Four hundred and one children (1.5-16 years) scheduled for daytime surgery were included. Children's anxiety during induction was rated by parents and anesthesiologists on a Visual Analog Scale and by a trained observer on the modified Yale Preoperative Anxiety Scale. Psychometric properties assessed were: (i) concurrent validity (correlations between parents' and anesthesiologists' Visual Analog Scale and modified Yale Preoperative Anxiety Scale scores); (ii) construct validity (differences between subgroups according to the children's age and the parents' anxiety as assessed by the State-Trait Anxiety Inventory); (iii) cross-informant agreement using Bland-Altman analysis; (iv) cut-offs to distinguish between anxious and nonanxious children (reference: modified Yale Preoperative Anxiety Scale ≥30). Results: Correlations between parents' and anesthesiologists' Visual Analog Scale and modified Yale Preoperative Anxiety Scale scores were strong (0.68 and 0.73, respectively). Visual Analog Scale scores were higher for children ≤5 years compared to children aged ≥6. Visual Analog Scale scores of children of high-anxious parents were higher than those of low-anxious parents. The mean difference between parents' and anesthesiologists' Visual Analog Scale scores was 3.6, with 95% limits of agreement (−56.1 to 63.3). To classify anxious children, cut-offs for parents (≥37 mm) and anesthesiologists (≥30 mm) were established. Conclusions: The present data provide preliminary data for the validity of a Visual Analog Scale to assess children's anxiety during induction. © 2017 John Wiley & Sons Ltd


Allegaert K.,University Hospitals Leuven | Cossey V.,University Hospitals Leuven | van den Anker J.N.,Childrens National Medical Center | van den Anker J.N.,George Washington University | And 2 more authors.
Current Pharmaceutical Design | Year: 2015

Once daily dosing of aminoglycosides has been introduced and validated in non-neonatal patient cohorts. This is because aminoglycosides display peak concentration dependent bacterial killing, have a post- antibiotic effect and adaptive resistance. In addition, this strategy reduces toxicity. Although aminoglycosides are also frequently administered to neonates, there is still debate about how to integrate and extrapolate these extended interval dosing regimens into dosing schedules tailored for neonates. There is a growing body of knowledge on Karel Allegaert aminoglycoside disposition and its covariates (e.g. asphyxia, ibuprofen or indomethacin exposure, serum creatinine, sepsis, dose accuracy) in neonates. In essence, integration of developmental physiology with clinical pharmacology unveils a discrepancy between aspects related to either body composition (higher distribution volume necessitates higher dose, to attain peak concentration) or to elimination clearance (lower renal clearance necessitates prolonged time interval between administrations). Such discrepancy can be solved by introducing more complex dosing guidelines (based on weight, postnatal age, serum creatinine, ibuprofen, asphyxia) in neonates. However, the introduction of more complex dosing guidelines should be balanced with its clinical feasibility. At least, there are reports that these more complex dosing guidelines result in a higher incidence of dosing errors. Besides errors in prescription, these errors also relate to the number of dilutions or manipulations needed before the prescribed dose can be administered. Since an integrated approach is needed, we discuss in this overview both the available pharmacokinetic data in support of the use of extended dosing regimens in neonates as well as the strategies suggested to reduce dosing errors. © 2015 Bentham Science Publishers.


Kloos R.Q.H.,Erasmus MCSophia Childrens Hospital | Pieters R.,Princess Maxima Center for Pediatric Oncology | Escherich G.,University of Hamburg | van der Sluis I.M.,Erasmus MCSophia Childrens Hospital
Pediatric Blood and Cancer | Year: 2016

Background: Asparaginase is an important component of pediatric acute lymphoblastic leukemia (ALL) therapy. Unfortunately, this treatment is hampered by hypersensitivity reactions. In general, allergies – regardless of severity – cause complete inactivation of the drug. However, we report atypical allergic reactions without inactivation of asparaginase, here called allergic-like reactions. Procedure: Patients with an allergic-like reaction, who were treated according to the Dutch Childhood Oncology Group ALL-11 or the CoALL 08–09 protocol, were described. The reactions were identified by continual measurement of asparaginase activity levels. Characteristics, including timing of occurrence, symptoms, grade, and the presence of antiasparaginase antibodies, were compared to those of real allergies. Results: Fourteen allergic-like reactions occurred in nine patients. Five reactions were to PEGasparaginase and nine to Erwinia asparaginase. Allergic-like reactions occurred relatively late after the start of infusion compared to real allergies. Antibodies were absent in all but one patient with an allergic-like reaction, while they were detected in all patients with a real allergy. Symptoms and grade did not differ between the groups. Asparaginase was continued with the same formulation in six patients of whom four finished treatment with adequate activity levels. Conclusions: In conclusion, allergic-like reactions occur relatively late after the start of infusion and without antibodies. Despite these clinical differences, allergic-like reactions can only be distinguished from real allergies by continually measuring asparaginase activity levels. If clinically tolerated, formulations should not be switched in case of allergic-like reactions. Moreover, failure to recognize these reactions may lead to a less favorable prognosis if asparaginase therapy is terminated unnecessarily. © 2016 Wiley Periodicals, Inc.


Buijs E.A.B.,Erasmus MC Sophia Childrens Hospital | Buijs E.A.B.,Erasmus Medical Center | Reiss I.K.M.,Erasmus MCSophia Childrens Hospital | Kraemer U.,Erasmus MC Sophia Childrens Hospital | And 4 more authors.
Pediatric Critical Care Medicine | Year: 2014

Objective: To study whether dopamine, norepinephrine, and epinephrine improve not only mean arterial blood pressure and heart rate but also microcirculatory perfusion in children with congenital diaphragmatic hernia. Design: Prospective observational cohort study from November 2009 to July 2012. Setting: ICU of a level III university children's hospital. Patients: Twenty-eight consecutive congenital diaphragmatic hernia newborns of whom seven did not receive any catecholaminergic support and 21 received dopamine as the drug of first choice. Fourteen of the latter also received either norepinephrine or epinephrine in addition to dopamine. Twenty-eight healthy neonates, matched for gestational age, postnatal age, and gender, served as controls. Interventions: None. Measurements and Main Results: Data were obtained before and after dopamine start and before and after norepinephrine or epinephrine start in case it was given. For the congenital diaphragmatic hernia without catecholaminergic support, data were obtained at admission days 1 and 2 and for the controls on day 1 of life. The buccal microcirculation was studied using Sidestream Dark Field imaging. Also macrocirculatory, respiratory, and biochemical variables were collected. Mean arterial blood pressure had improved after dopamine start, whereas the microcirculation had not. After the start of either norepinephrine or epinephrine, both blood pressure and heart rate had increased. However, the microcirculation failed to improve again. The microcirculation in the healthy controls was better than that in the congenital diaphragmatic hernia patients with catecholaminergic support. After cutoff values for abnormal microcirculation had been defined, abnormal microcirculation after dopamine start predicted the need for additional catecholaminergic support (area under the curve, 0.74-0.88; sensitivity, 77-77%; specificity, 69-77%). Likewise, microcirculatory impairment was associated with the need for extracorporeal membrane oxygenation. Conclusions: Catecholaminergic drug support with dopamine, norepinephrine, and/or epinephrine improved macrocirculatory function but did not improve the microcirculation in neonates with congenital diaphragmatic hernia. The microcirculation was not only impaired but it also predicted poor outcome. Copyright © 2014 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.


Cuypers J.A.A.E.,Erasmus University Rotterdam | Menting M.E.,Erasmus University Rotterdam | Opic P.,Erasmus University Rotterdam | Utens E.M.W.J.,Erasmus MCSophia Childrens Hospital | And 9 more authors.
Heart | Year: 2016

Objective To provide prospective information on long-term outcome after surgical correction of valvular pulmonary stenosis (PS). Methods Fifty-three consecutive patients operated for PS during childhood between 1968 and 1980 in one centre are followed longitudinally for 37±3.4 years, including extensive in-hospital examination every 10 years. Results Survival information was available in 100% of the original 53 patients. Cumulative survival was 94% at 20 years and 91% at 40 years. Excluding perioperative mortality (<30 days), survival was 94% at 40 years. Of 46 eligible survivors, 29 participated in the in-hospital examination and 15 gave permission to use their hospital records (96% participation). Cumulative eventfree survival was 68% after 40 years: 25% needed a reintervention, 12% underwent pacemaker implantation and 9% had supraventricular arrhythmias. Early reinterventions were mainly for residual PS, late reinterventions for pulmonary regurgitation. Subjective health status was good. Exercise capacity was normal in 74% (median 96 (82-107)% of expected workload). Right ventricular and left ventricular (LV) dysfunction was found in 13% and 41%, respectively. The use of a transannular patch and younger age at surgery were predictive for late events (HR 3.02 (95% CI 1.09 to 8.37) and HR 0.81/year (95% CI 0.66 to 0.98), respectively). Use of inflow occlusion compared with cardiopulmonary bypass showed a trend towards more reinterventions (HR 3.19 (95% CI 0.97 to 10.47)). Conclusions Survival up to 40 years after successful PS repair is nearly normal. Subjective health status is good and there is a low incidence of arrhythmias. Reinterventions, however, are necessary in one-quarter and 40 years postoperatively several patients show LV dysfunction. © 2016 BMJ Publishing Group Ltd & British Cardiovascular Society.


Roofthooft D.W.E.,Erasmus Mcsophia Childrens Hospital | van Beynum I.M.,Erasmus Mcsophia Childrens Hospital | de Klerk J.C.A.,Erasmus Mcsophia Childrens Hospital | van Dijk M.,Erasmus Mcsophia Childrens Hospital | And 5 more authors.
European Journal of Pediatrics | Year: 2015

Finding the optimal pharmacological treatment of a patent ductus arteriosus (PDA) in preterm neonates remains challenging. There is a growing interest in paracetamol as a new drug for PDA closure. In this prospective observational cohort study, we evaluated the effectiveness of intravenous paracetamol in closing a PDA in very low birth weight infants with a hemodynamically significant PDA who either did not respond to ibuprofen or had a contraindication for ibuprofen. They received high-dose paracetamol therapy (15 mg/kg/6 h intravenous) for 3–7 days. Cardiac ultrasounds were performed before and 3 and 7 days after treatment. Thirty-three patients were included with a median gestational age of 251/7 weeks (IQR 1.66), a median birth weight of 750 g (IQR 327), and a median postnatal age of 14 days (IQR 12). Paracetamol was ineffective in 27/33 patients (82 %). Even more, after previous exposure to ibuprofen, this was even 100 %. Conclusion: In this study, paracetamol after ibuprofen treatment failure was not effective for PDA closure in VLBW infants. From the findings of this study, paracetamol treatment for PDA closure cannot be recommended for infants with a postnatal age >2 weeks. Earlier treatment with paracetamol for PDA might be more effective.What is known:• The ductus arteriosus fails to close after birth in 30 to 60 % of prematurely born neonates and is a significant cause of morbidity and mortality in these infants.• Paracetamol gained importance as an alternative drug in PDA closure.What is new:• Paracetamol for PDA closure after ibuprofen treatment failure was not effective in VLBW infants.• Effect of paracetamol on PDA closure was observed when given as primary treatment. © 2015, The Author(s).


Duijkers F.A.M.,Erasmus MCSophia Childrens Hospital | De Menezes R.X.,Erasmus MCSophia Childrens Hospital | De Menezes R.X.,VU University Amsterdam | Goossens-Beumer I.J.,Erasmus MCSophia Childrens Hospital | And 5 more authors.
Cellular Oncology | Year: 2013

Background Epigenetic alterations are inherent to cancer cells, and epigenetic drugs are currently primarily used to treat hematological malignancies. Pediatric neuro-ectodermal tumors originate from neural crest cells and also exhibit epigenetic alterations involving e.g. apoptotic pathways, which suggests that these tumors may also be sensitive to epigenetic drugs. This notion prompted us to assess molecular and functional effects of low dosage epigenetic drugs in neuroectodermal tumor-derived cell lines of pediatric origin. Results In 17 neuroblastoma (NBL) and 5 peripheral primitive neuro-ectodermal tumor (PNET) cell lines a combination treatment of 5-aza-2'-deoxycytidine (DAC) and Trichostatin A (TSA) at nanomolar dosages was found to reduce proliferation and to induce wide-spread DNA demethylation, accompanied by major changes in gene expression profiles. Approximately half of the genes that were significantly up-regulated upon treatment exhibited a significant demethylation in their promoter regions. In the NBL cell lines, almost every cellular pathway (193/200) investigated showed expression alterations after treatment, especially a marked up-regulation of genes in the p53 pathway. The combination treatment also resulted in up-regulation of known epigenetically regulated genes such as X-chromosomal genes, tissue-specific genes and a limited number of imprinted genes, as well as known tumor suppressor genes and oncogenes. Conclusions Nanomolar dosages of epigenetic drugs have a dramatic impact on the genomes of neuro-ectodermal tumorderived cell lines, including alterations in DNA methylation and concomitant alterations in gene expression. © International Society for Cellular Oncology 2013.

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