St Jansdal Hospital

Harderwijk, Netherlands

St Jansdal Hospital

Harderwijk, Netherlands

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ten Dam E.,University of Groningen | van der Heijden P.,St Jansdal Hospital | Korsten-Meijer A.G.W.,University of Groningen | Goorhuis-Brouwer S.M.,University of Groningen
International Journal of Pediatric Otorhinolaryngology | Year: 2013

Objectives: To evaluate the frequency of submucous cleft palate (SMCP) in a group of children with clefts. The reason for suspecting submucous cleft, age of diagnosis, effect of age on speech development, problems in speech, hearing and swallowing were compared with previous literature. Methods: Retrospective chart review: Out of 33 patients with SMCP, registered by the Groninger cleft team over approximately 20 years (1990 until July 2012), 28 non-syndromic patients with a proven diagnosis of SMCP were included: 17 males and 11 females. Speech and hearing were examined and the number of patients with SMCP and age at time of diagnosis were evaluated. The percentages of problems in resonance, articulation and hearing, present at time of diagnosis, were compared with the percentages of problems found after surgery. Results: Out of 800 patients with clefts, 28 patients (3,5%) were diagnosed with SMCP at a mean age of 3;9 years. All patients presented one or more symptomatic complaints at time of diagnosis: hypernasality (65%), problems in articulation (46%), conductive hearing loss (39%) and/or swallowing problems (32%). A bifid uvula was found in 92%. Following surgery, hypernasal speech and swallowing problems were no longer observed. The articulation problems remained after surgery. Age of diagnosis seems no predictor of articulation problems. An improvement in hearing was observed but normal hearing was not achieved. Pharyngoplasty appeared to be a successful and save treatment of hypernasality. Conclusions: SMCP is a rare cleft palate which is, despite the presence of a bifid uvula and symptoms of velopharyngeal insufficiency, often diagnosed late. In children with a bifid uvula and mild problems in speech, hearing and swallowing, it is important to be alert to SMCP because SMCP may account for these persistent mild complaints. Therefore, early detecting of SMCP can yield profits. © 2013 Elsevier Ireland Ltd.


Garon E.B.,University of California at Los Angeles | Ciuleanu T.-E.,University of Medicine and Pharmacy, Cluj-Napoca | Arrieta O.,Instituto Nacional Of Cancerologia Incan | Prabhash K.,Tata Memorial Center | And 20 more authors.
The Lancet | Year: 2014

Background Ramucirumab is a human IgG1 monoclonal antibody that targets the extracellular domain of VEGFR-2. We aimed to assess efficacy and safety of treatment with docetaxel plus ramucirumab or placebo as second-line treatment for patients with stage IV non-small-cell-lung cancer (NSCLC) after platinum-based therapy. Methods In this multicentre, double-blind, randomised phase 3 trial (REVEL), we enrolled patients with squamous or non-squamous NSCLC who had progressed during or after a first-line platinum-based chemotherapy regimen. Patients were randomly allocated (1:1) with a centralised, interactive voice-response system (stratified by sex, region, performance status, and previous maintenance therapy [yes vs no]) to receive docetaxel 75 mg/m 2 and either ramucirumab (10 mg/kg) or placebo on day 1 of a 21 day cycle until disease progression, unacceptable toxicity, withdrawal, or death. The primary endpoint was overall survival in all patients allocated to treatment. We assessed adverse events according to treatment received. This study is registered with ClinicalTrials.gov, number NCT01168973. Findings Between Dec 3, 2010, and Jan 24, 2013, we screened 1825 patients, of whom 1253 patients were randomly allocated to treatment. Median overall survival was 10·5 months (IQR 5·1-21·2) for 628 patients allocated ramucirumab plus docetaxel and 9·1 months (4·2-18·0) for 625 patients who received placebo plus docetaxel (hazard ratio 0·86, 95% CI 0·75-0·98; p=0·023). Median progression-free survival was 4·5 months (IQR 2·3-8·3) for the ramucirumab group compared with 3·0 months (1·4-6·9) for the control group (0·76, 0·68-0·86; p<0·0001). We noted treatment-emergent adverse events in 613 (98%) of 627 patients in the ramucirumab safety population and 594 (95%) of 618 patients in the control safety population. The most common grade 3 or worse adverse events were neutropenia (306 patients [49%] in the ramucirumab group vs 246 [40%] in the control group), febrile neutropenia (100 [16%] vs 62 [10%]), fatigue (88 [14%] vs 65 [10%]), leucopenia (86 [14%] vs 77 [12%]), and hypertension (35 [6%] vs 13 [2%]). The numbers of deaths from adverse events (31 [5%] vs 35 [6%]) and grade 3 or worse pulmonary haemorrhage (eight [1%] vs eight [1%]) did not differ between groups. Toxicities were manageable with appropriate dose reductions and supportive care. Interpretation Ramucirumab plus docetaxel improves survival as second-line treatment of patients with stage IV NSCLC. Funding Eli Lilly. © 2014 Elsevier Ltd.


De Vos A.,St Jansdal Hospital | Van Der Weide J.,St Jansdal Hospital | Van Der Weide J.,Psychiatric Hospital Meerkanten | Loovers H.M.,St Jansdal Hospital | Loovers H.M.,Psychiatric Hospital Meerkanten
Pharmacogenomics Journal | Year: 2011

Polymorphisms in genes coding for drug metabolizing enzymes, such as the cytochrome P450 enzymes CYP2C19 and CYP2D6, can lead to therapy failure and side effects. In earlier studies, the novel variant CYP2C1917 increased metabolism of several CYP2C19 substrates. The objective of this study was to evaluate the impact of CYP2C1917 on the metabolism of amitriptyline (AT), citalopram (CIT), and clomipramine (CLOM). Six-hundred and seventy-eight patients were included in this study, based on availability of DNA and serum levels of parent drug and main metabolite. We investigated the relationship between CYP2C19 genotypes and metabolic parameters, including serum levels corrected for dose and metabolic ratio (MR). The CYP2C1917 allele was significantly associated with decreased MR for CIT (CYP2C191/17 mean MR2.3, compared with CYP2C191/1 mean MR2.8) and AT (CYP2C1917/17 mean MR0.8, compared with CYP2C191/1 mean MR3.7 in the CYP2D61/1 subgroup). Furthermore, significant association of CYP2D6 genotype with AT, CIT, and CLOM metabolism was observed. No clear correlation was found between CYP2C19 genotype and CLOM metabolism. This study confirms the increased activity of the CYP2C1917 allele and shows increased metabolism of drugs that are metabolized by CYP2C19, including AT and CIT. However, the clinical relevance of CYP2C1917 is probably limited for AT, CIT, and CLOM. © 2011 Micmillan Publishers Limited. All rights reserved.


Bakker M.F.,University Utrecht | Jacobs J.W.G.,University Utrecht | Welsing P.M.J.,University Utrecht | Verstappen S.M.M.,Arthritis Research UK Epidemiology Unit | And 10 more authors.
Annals of Internal Medicine | Year: 2012

Background: Treatment strategies for tight control of early rheumatoid arthritis (RA) are highly effective but can be improved. Objective: To investigate whether adding prednisone, 10 mg/d, at the start of a methotrexate (MTX)-based treatment strategy for tight control in early RA increases its effectiveness. Design: A 2-year, prospective, randomized, placebo-controlled, double-blind, multicenter trial (CAMERA-II [Computer Assisted Management in Early Rheumatoid Arthritis trial-II]). (International Standard Randomised Controlled Trial Number: ISRCTN 70365169) Setting: 7 hospitals in the Netherlands. Patients: 236 patients with early RA (duration <1 year). Intervention: Patients were randomly assigned to an MTX-based, tight control strategy starting with either MTX and prednisone or MTX and placebo. Methotrexate treatment was tailored to the individual patient at monthly visits on the basis of predefined response criteria aiming for remission. Measurements: The primary outcome was radiographic erosive joint damage after 2 years. Secondary outcomes included response criteria, remission, and the need to add cyclosporine or a biologic agent to the treatment. Results: Erosive joint damage after 2 years was limited and less in the group receiving MTX and prednisone (n = 117) than in the group receiving MTX and placebo (n = 119). The MTX and prednisone strategy was also more effective in reducing disease activity and physical disability, achieving sustained remission, and avoiding the addition of cyclosporine or biologic treatment. Adverse events were similar in both groups, but some occurred less in the MTX and prednisone group. Limitation: A tight control strategy for RA implies monthly visits to an outpatient clinic, which is not always feasible. Conclusion: Inclusion of low-dose prednisone in an MTX-based treatment strategy for tight control in early RA improves patient outcomes. © 2012 American College of Physicians.


Van Der Weide K.,St Jansdal Hospital | Van Der Weide J.,St Jansdal Hospital | Van Der Weide J.,Psychiatric Hospital GGz Centraal
Journal of Clinical Psychopharmacology | Year: 2014

BACKGROUND: Besides dietary, hormonal, or pathological factors, mutations in cytochrome P450 enzymes are thought to be responsible for the interindividual differences in serum concentrations of cytochrome P450 (CYP450)-dependent drugs. Cytochrome P450 3A4 (CYP3A4) is involved in the metabolism of greater than 50% of the prescribed drugs. Recently, a new single-nucleotide polymorphism (SNP) was found (CYP3A4*22), which results in a decreased enzyme activity, in contrast to the other known SNPs in CYP3A4. We investigated to which degree the CYP3A4*22 SNP affects serum concentrations of patients receiving quetiapine, a drug exclusively metabolized by CYP3A4. METHODS: Two hundred thirty-eight adult patients receiving quetiapine were included in this study, based on availability of DNA, serum quetiapine levels, and information on dose. Patients were genotyped for CYP3A4*22 using allele-specific polymerase chain reaction, and, as a control, restriction fragment length polymorphism analysis. RESULTS: Carriers of the CYP3A4*22 allele (*1/*22 and *22/*22, n = 31) had 2.5-fold higher serum levels of quetiapine than did wild-type patients (n = 207; P = 0.03) when using a comparable dose (median, 300 mg/d for both wild-type and carriers; P = 0.67). The dose-corrected serum concentration (C/D) was 67% higher in carriers than in wild-type patients (P = 0.01). The number of patients who achieved serum levels above the therapeutic range (>500 μg/L) was also higher in *22-allele carriers (16.1% vs 2.9%; P = 0.007). CONCLUSION: Being a carrier of the CYP3A4*22 allele increases the serum concentration of quetiapine at comparable doses. Copyright © 2014 by Lippincott Williams & Wilkins.


Van Der Goes M.C.,University Utrecht | Jacobs J.W.G.,University Utrecht | Jurgens M.S.,University Utrecht | Bakker M.F.,University Utrecht | And 4 more authors.
Osteoporosis International | Year: 2013

Summary: Addition of 10 mg prednisone daily to a methotrexate-based tight control strategy does not lead to bone loss in early rheumatoid arthritis (RA) patients receiving preventive treatment for osteoporosis. A small increase in lumbar bone mineral density (BMD) during the first year of treatment was recorded, regardless of use of glucocorticoids. Introduction: This study aims to describe effects on BMD of treatment according to EULAR guidelines with a methotrexate-based tight control strategy including 10 mg prednisone daily versus the same strategy without prednisone in early RA patients who received preventive therapy for osteoporosis. Methods: Early RA patients were included in the CAMERA-II trial: a randomized, placebo-controlled, double-blind 2-year trial, in which effects of addition of 10 mg prednisone daily to a methotrexate-based tight control strategy were studied. All patients received calcium, vitamin D and bisphosphonates. Disease activity was assessed every 4 weeks. Radiographs of hands and feet and dual-energy X-ray absorptiometry of lumbar spine and left hip were performed at baseline and after 1 and 2 years of treatment. Results: BMD increased significantly over time in both treatment groups at the lumbar spine with a mean of 2.6 % during the first year (p < 0.001), but not at the hip; at none of the time points did BMD differ significantly between the prednisone and placebo group. Higher age and lower weight at baseline and higher disease activity scores during the trial, but not glucocorticoid therapy, were associated with lower BMD at both the lumbar spine and the hip in mixed-model analyses. Conclusion: Addition of 10 mg prednisone daily to a methotrexate-based tight control strategy does not lead to bone loss in early RA patients on bisphosphonates. A small increase in lumbar BMD during the first year of treatment was found, regardless of use of glucocorticoids. © 2012 The Author(s).


Bakker M.F.,University Utrecht | Jacobs J.W.G.,University Utrecht | Kruize A.A.,University Utrecht | Van Der Veen M.J.,St Jansdal Hospital | And 5 more authors.
Annals of the Rheumatic Diseases | Year: 2012

Objective: To study whether assessment of rheumatoid arthritis (RA) disease activity in individual patients using the disease activity score in 28 joints (DAS28) or other instruments excluding joints of feet may lead to misclassification of disease activity. Methods: A cohort of RA patients was classified into three 'regional radiographic damage progression' groups: predominantly progression in feet, similar progression in hands and feet and predominantly progression in hands; both in early (0-2 years) and later (2-5 years) disease. Baseline and mean DAS28, individual DAS28 variables and tender joint counts (TJC) and swollen joint counts (SJC) of the feet were compared between groups. The longitudinal relation of DAS28 with radiographic damage was investigated using a mixed model analysis with rheumatoid factor status, baseline joint damage and TJC and SJC of the feet as covariates. Results: Early (n=265) and later (n=200) in the disease course, by definition, the classification procedure resulted in 25% as predominantly foot, 25% as predominantly hand and 50% as similar progressors. In early RA predominantly foot progressors had higher TJC and SJC of the feet compared with predominantly hand progressors (p<0.001), but DAS28 was similar. This was not seen in later disease. The longitudinal relation between DAS28 and radiographic progression was influenced by the region of progression (predominantly foot progressors vs others, p<0.001), suggesting that DAS28 underestimates disease activity in predominantly foot progressors. In this group, joint counts for the feet were independently related to radiographic progression. Conclusions: DAS28 underestimates actual disease activity and expected joint damage of individual early RA patients predominantly with disease in the feet.


van der Weide K.,St Jansdal Hospital
Pharmacogenomics Journal | Year: 2016

Prescription of clozapine is complicated by the occurrence of clozapine-induced reduction of neutrophils. The aim of this study was to identify genetic risk factors in a population of 310 Dutch patients treated with clozapine, including 38 patients developing neutropenia and 31 patients developing agranulocytosis. NQO2 1541AA (NRH quinone oxidoreductase 2; protects cells against oxidative metabolites) was present at a higher frequency in agranulocytosis patients compared with control (23% versus 7%, P=0.03), as was ABCB1 (ABC-transporter-B1; drug efflux transporter) 3435TT (32% versus 20%, P=0.05). In patients developing neutropenia, ABCB1 3435TT and homozygosity for GSTT1null (glutathione-S-transferase; conjugates reactive clozapine metabolites into glutathione) were more frequent compared with control (34% versus 20%, P=0.05 and 31% versus 14%, P=0.03), whereas GSTM1null was less frequent in these patients (31% versus 52%, P=0.03). To investigate whether combinations of the identified genetic risk factors have a higher predictive value, should be confirmed in a larger case–control study.The Pharmacogenomics Journal advance online publication, 10 May 2016; doi:10.1038/tpj.2016.32. © 2016 Macmillan Publishers Limited


Van Der Weide K.,St Jansdal Hospital | Van Der Weide J.,St Jansdal Hospital
Journal of Clinical Psychopharmacology | Year: 2015

Cytochrome P450 3A4 (CYP3A4) is involved in the metabolism of greater than 50% of the prescribed drugs. Recently, the CYP3A4∗22 allele was reported to be associated with lower CYP3A4 expression and activity. Quetiapine, an antipsychotic metabolized by only CYP3A4, displayed higher serum levels in CYP3A4∗22 carriers. Aripiprazole, haloperidol, pimozide, and risperidone are antipsychotics that are metabolized by CYP3A4 and CYP2D6. We investigated to which degree the CYP3A4∗22 single-nucleotide polymorphism affects serum concentrations of patients receiving these drugs and compared this with the influence of CYP2D6 polymorphisms. Methods: Eight hundred thirty-four adult patients were included in this study, of whom 130 used aripiprazole, 312 used haloperidol, 86 used pimozide, and 396 used risperidone. Serum levels of the drug and, if available, their active metabolites were collected as well as information on dose. Patients were genotyped for CYP3A4∗22 using restriction fragment length polymorphism analysis. Genotyping for CYP2D6 was done with allelespecific polymerase chain reaction. Results: No differences were found in serum (dose-corrected) concentrations of the antipsychotics between CYP3A4∗22 wild-type and carrier groups. In contrast, CYP2D6 genotype did affect dose-corrected concentrations of the antipsychotics: for example, median dose-corrected concentrations were 56%, 86%, and 400% higher in predicted poor metabolizers versus extensive metabolizers for aripiprazole (P = 0.004), haloperidol (P > 0.001), and risperidone (P < 0.001), respectively, although a multiple regression analysis showed that only 4% to 17% of the variation in these concentrations could be explained by CYP2D6 status. Conclusions: Heterozygous presence of CYP3A4∗22 does not increase serum levels of antipsychotics metabolized by both CYP3A4 and CYP2D6, whereas CYP2D6 polymorphisms do affect serum levels to a limited extent. © 2015 Wolters Kluwer Health, Inc. All rights reserved.


Van Der Heijden P.,St Jansdal Hospital | Dijkstra P.U.,St Jansdal Hospital | Stellingsma C.,St Jansdal Hospital | Van Der Laan B.F.,St Jansdal Hospital | And 2 more authors.
Plastic and Reconstructive Surgery | Year: 2013

Background:: In the past two decades, presurgical nasoalveolar molding has been applied increasingly in the care of patients with a cleft to improve nasal symmetry and facilitate closure of the lip and secondary rhinoplasty. Many cleft centers do not apply presurgical molding, because its effect is disputed. This review aims to quantify the effect of nasal symmetry in the long term. Methods:: A systematic review of the literature with the intention of performing a meta-analysis was performed. The search terms "cleft" AND ("molding" OR "moulding") were used in three databases. Twelve studies met the following inclusion criteria: (1) participants were humans with nonsyndromic unilateral cleft; (2) data concerning the effect of nasoalveolar molding on symmetry of the nose are reported or can be deduced; (3) article was written in English, German, or Dutch. Results:: The heterogeneity of the study designs, outcome variables, outcome variable expressions, follow-up periods, and inadequate data reporting made it impossible to calculate effect sizes and to perform a meta-analysis. All studies had a low Grading of Recommendations Assessment, Development and Evaluation level. Five studies reported exclusively positive effects on nasal symmetry, six studies reported mixed effects, and one study reported exclusively no effects. Conclusions:: Results of studies of nasoalveolar molding are inconsistent regarding changes in nasal symmetry; however, there is a trend toward a positive effect. Studies concerning nasoalveolar molding in unilateral cleft lip, jaw, and palate are heterogeneous and lack adequate reporting. Recommendations for future research were provided to construct a consensus about the effect of nasoalveolar molding. Clinical Question/Level of Evidence:: Therapeutic, III. © 2012 by the American Society of Plastic Surgeons.

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