Johan L Severens

Erasmus Universiteit Rotterdam, Rotterdam, South Holland, Netherlands

Are you Johan L Severens?

Claim your profile

Publications (157)557.35 Total impact

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Most studies on birth settings investigate the association between planned place of birth at the start of labor and birth outcomes and intervention rates. To optimize maternity care it also is important to pay attention to the entire process of pregnancy and childbirth. This study explores the association between the initial preferred place of birth and model of care, and the course of pregnancy and labor in low-risk nulliparous women in the Netherlands. As part of a Dutch prospective cohort study (2007-2011), we compared medical indications during pregnancy and birth outcomes of 576 women who initially preferred a home birth (n = 226), a midwife-led hospital birth (n = 168) or an obstetrician-led hospital birth (n = 182). Data were obtained by a questionnaire before 20 weeks of gestation and by medical records. Analyses were performed according to the initial preferred place of birth. Low-risk nulliparous women who preferred a home birth with midwife-led care were less likely to be diagnosed with a medical indication during pregnancy compared to women who preferred a birth with obstetrician-led care (OR 0.41 95% CI 0.25-0.66). Preferring a birth with midwife-led care - both at home and in hospital - was associated with lower odds of induced labor (OR 0.51 95% CI 0.28-0.95 respectively OR 0.42 95% CI 0.21-0.85) and epidural analgesia (OR 0.32 95% CI 0.18-0.56 respectively OR 0.34 95% CI 0.19-0.62) compared to preferring a birth with obstetrician-led care. In addition, women who preferred a home birth were less likely to experience augmentation of labor (OR 0.54 95% CI 0.32-0.93) and narcotic analgesia (OR 0.41 95% CI 0.21-0.79) compared to women who preferred a birth with obstetrician-led care. We observed no significant association between preferred place of birth and mode of birth. Nulliparous women who initially preferred a home birth were less likely to be diagnosed with a medical indication during pregnancy. Women who initially preferred a birth with midwife-led care - both at home and in hospital - experienced lower rates of interventions during labor. Although some differences can be attributed to the model of care, we suggest that characteristics and attitudes of women themselves also play an important role.
    BMC Pregnancy and Childbirth 12/2015; 15(1):455. DOI:10.1186/s12884-015-0455-x · 2.19 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Purpose: Fluoropyrimidines are frequently prescribed anticancer drugs. A polymorphism in the fluoropyrimidine metabolizing enzyme dihydropyrimidine dehydrogenase (DPD; ie, DPYD*2A) is strongly associated with fluoropyrimidine-induced severe and life-threatening toxicity. This study determined the feasibility, safety, and cost of DPYD*2A genotype-guided dosing. Patients and methods: Patients intended to be treated with fluoropyrimidine-based chemotherapy were prospectively genotyped for DPYD*2A before start of therapy. Variant allele carriers received an initial dose reduction of ≥ 50% followed by dose titration based on tolerance. Toxicity was the primary end point and was compared with historical controls (ie, DPYD*2A variant allele carriers receiving standard dose described in literature) and with DPYD*2A wild-type patients treated with the standard dose in this study. Secondary end points included a model-based cost analysis, as well as pharmacokinetic and DPD enzyme activity analyses. Results: A total of 2,038 patients were prospectively screened for DPYD*2A, of whom 22 (1.1%) were heterozygous polymorphic. DPYD*2A variant allele carriers were treated with a median dose-intensity of 48% (range, 17% to 91%). The risk of grade ≥ 3 toxicity was thereby significantly reduced from 73% (95% CI, 58% to 85%) in historical controls (n = 48) to 28% (95% CI, 10% to 53%) by genotype-guided dosing (P < .001); drug-induced death was reduced from 10% to 0%. Adequate treatment of genotype-guided dosing was further demonstrated by a similar incidence of grade ≥ 3 toxicity compared with wild-type patients receiving the standard dose (23%; P = .64) and by similar systemic fluorouracil (active drug) exposure. Furthermore, average total treatment cost per patient was lower for screening (€2,772 [$3,767]) than for nonscreening (€2,817 [$3,828]), outweighing screening costs. Conclusion: DPYD*2A is strongly associated with fluoropyrimidine-induced severe and life-threatening toxicity. DPYD*2A genotype-guided dosing results in adequate systemic drug exposure and significantly improves safety of fluoropyrimidine therapy for the individual patient. On a population level, upfront genotyping seemed cost saving.
    Journal of Clinical Oncology 11/2015; DOI:10.1200/JCO.2015.63.1325 · 18.43 Impact Factor
  • AS Grustam · JL Severens · D de Massari · R Koymans · H Vrijhoef ·

    Value in Health 11/2015; 18(7):A358. DOI:10.1016/j.jval.2015.09.681 · 3.28 Impact Factor
  • A Tran-Duy · A Boonen · JJ Caro · JL Severens ·

    Value in Health 11/2015; 18(7):A700. DOI:10.1016/j.jval.2015.09.2618 · 3.28 Impact Factor
  • Source
    An Tran-Duy · Annelies Boonen · Mart A F J van de Laar · Johan L Severens ·
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: Sequential treatment of ankylosing spondylitis (AS) that includes tumour necrosis factor-α antagonists (anti-TNF agents) has been applied in most of the Western countries. Existing cost-effectiveness (CE) models almost exclusively presented the incremental CE of anti-TNF agents using a closed cohort while budget impact studies are mainly lacking. Notwithstanding, information on impact on total population health and societal budget as well as on actual incremental CE for a given decision time span are important for decision makers. This study aimed at quantifying, for different decision time spans starting from January 1, 2014 in the Dutch society, (1) impact of sequential drug treatment strategies without and with inclusion of anti-TNF agents (Strategies 1 and 2, respectively) on total population health and societal cost, and (2) the actual incremental CE of Strategy 2 compared to Strategy 1. Methods: Dynamic population modelling was used to capture total population health and cost, and the actual incremental CE. Distinguishing the prevalent AS population on January 1, 2014 and the incident AS cohorts in the subsequent 20 years, the model tracked individually an actual number of AS patients until death or end of the simulation time. During the simulation, data on patient characteristics, history of drug use, costs and health at discrete time points were generated. In Strategy 1, five nonsteroidal anti-inflammatory drugs (NSAIDs) were available but anti-TNF agents withdrawn. In Strategy 2, five NSAIDs and two anti-TNF agents continued to be available. Results: The predicted size of the prevalent AS population in the Dutch society varied within the range of 67,145-69,957 with 44-46 % of the patients receiving anti-TNF agents over the period 2014-2034. The use of anti-TNF agents resulted in an increase in the annual drug costs (168.54-205.28 million Euros), but at the same time caused a decrease in the annual productivity costs (12.58-31.21 million Euros) and in annual costs of healthcare categories other than drugs (7.23-11.90 million Euros). Incremental cost (Euros) per QALY gained in Strategy 2 compared to Strategy 1 corresponding to decision time spans of 5, 10, 15 and 20 years improved slightly from 75,379 to 67,268, 63,938 and 61,129, respectively. At willingness-to-pay thresholds of 118,656, 112,067, 110,188 and 110,512 Euros, it was 99 % certain that Strategy 2 was cost-effective for decision time spans of 5, 10, 15 and 20, respectively. Conclusions: Using the dynamic population approach, the present model can project real-time data to inform a healthcare system decision that affects all actual number of AS patients eligible for anti-TNF agents within different decision time spans. The predicted total population costs of different categories in the present study can help plan the organization of the healthcare resources based on the national budget for the disease.
    Cost Effectiveness and Resource Allocation 10/2015; 13(1):18. DOI:10.1186/s12962-015-0044-x · 0.87 Impact Factor
  • Source

  • Source
    Olena Mandrik · Isaac Corro Ramos · Saskia Knies · Maiwenn Al · Johan L Severens ·
    [Show abstract] [Hide abstract]
    ABSTRACT: Abstract: The aim of this study was to assess the cost-effectiveness, from a health care perspective, of adding rituximab to fludarabine and cyclophosphamide scheme (FCR versus FC) for treatment-naïve and refractory/relapsed Ukrainian patients with chronic lymphocytic leukemia. A decision-analytic Markov cohort model with three health states and 1-month cycle time was developed and run within a life time horizon. Data from two multinational, prospective, open-label Phase 3 studies were used to assess patients' survival. While utilities were generalized from UK data, local resource utilization and disease-associated treatment, hospitalization, and side effect costs were applied. The alternative scenario was performed to assess the impact of lower life expectancy of the general population in Ukraine on the incremental cost-effectiveness ratio (ICER) for treatment-naïve patients. One-way, two-way, and probabilistic sensitivity analyses were conducted to assess the robustness of the results. The ICER (in US dollars) of treating chronic lymphocytic leukemia patients with FCR versus FC is US$8,704 per quality-adjusted life year gained for treatment-naïve patients and US$11,056 for refractory/relapsed patients. When survival data were modified to the lower life expectancy of the general population in Ukraine, the ICER for treatment-naïve patients was higher than US$13,000. This value is higher than three times the current gross domestic product per capita in Ukraine. Sensitivity analyses have shown a high impact of rituximab costs and a moderate impact of differences in utilities on the ICER. Furthermore, probabilistic sensitivity analyses have shown that for refractory/relapsed patients the probability of FCR being cost-effective is higher than for treatment-naïve patients and is close to one if the threshold is higher than US$15,000. State coverage of rituximab treatment may be considered a cost-effective treatment for the Ukrainian population under conditions of economic stability, cost-effectiveness threshold growth, or rituximab price negotiations.
    Cancer Management and Research 08/2015; 7. DOI:10.2147/CMAR.S79258
  • Gerardus Wj Frederix · Johan L Severens · Anke M Hövels ·
    [Show abstract] [Hide abstract]
    ABSTRACT: Economic evaluations have become an essential part of reimbursement decisions in a wide range of countries. To ensure high quality, a variety of checklists with different purposes have been developed and implemented enabling assessment of these evaluations. Three of these checklists are most frequently used and are recommended by the Cochrane Handbook for Systematic Reviews for critical appraisal (Drummond, CHEC and Philips). Every checklist is developed with a different purpose having, for example, a focus on reporting or conducting and on modeling or trial-based evaluations. This review outlines the heterogeneity in choice and implementation of these quality checklists in an incorrect manner. This ultimately results in under- and even possibly overestimation of quality of included economic evaluations. More guidance in selecting correct checklists suiting the purpose of the quality check is therefore of utmost importance. Moreover, it appears that current checklists are lacking detailed disease-specific guidance resulting in models not correctly reflecting disease progression. Therefore, outcomes indicate that the problem of the wide variability of methodological choices is prevalent in some other disease areas too, regardless of the availability of quality checklists. More international collaboration should therefore be initiated in developing and publishing standardized and open source disease-specific reference models to overcome this problem.
    Expert Review of Pharmacoeconomics & Outcomes Research 08/2015; 15(4):675-85. DOI:10.1586/14737167.2015.1069185 · 1.67 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: - There is increasing discussion in the Netherlands about the introduction of a threshold value for the costs per extra year of life when reimbursing costs of new drugs. - The Medicines Committee ('Commissie Geneesmiddelen'), a division of the Netherlands National Healthcare Institute ('Zorginstituut Nederland'), advises on reimbursement of costs of new drugs. - This advice is based upon the determination of therapeutic value of the drug and the results of economic evaluations.- Mathematical models that predict future costs and effectiveness are often used in economic evaluations; these models can vary greatly in transparency and quality due to author assumptions.- Standardisation of cost-effectiveness models is one solution to overcome the unwanted variation in quality.- Discussions about the introduction of a threshold value can only be meaningful if all involved are adequately informed, and by high quality in cost-effectiveness research and, particularly, economic evaluations.- Collaboration and discussion between medical specialists, patients or patient organisations, health economists and policy makers, both in development of methods and in standardisation, are essential to improve the quality of decision making.
    Nederlands tijdschrift voor geneeskunde 06/2015; 159:A7728.
  • Source
    Olena Mandrik · Saskia Knies · Johan L Severens ·
    [Show abstract] [Hide abstract]
    ABSTRACT: An economic value calculation was performed to estimate the lifetime net present value of in vitro fertilization (IVF) in Ukraine, Belarus, and Kazakhstan. Net lifetime tax revenues were used to represent governmental benefits accruing from a hypothetical cohort of an IVF population born in 2009 using the methodology of generational accounting. Governmental expenses related to this population included social benefits, education and health care, unemployment support, and pensions. Where available, country-specific data referencing official sources were applied. The average health care cost needed to achieve one additional birth from the governmental perspective varied from $2,599 in Ukraine to $5,509 in Belarus. The net present value from the population born using IVF was positive in all countries: for Ukraine ($9,839), Belarus ($21,702), and Kazakhstan ($2,295). The break-even costs of drugs and supplies per IVF procedure is expected to be $3,870, $8,530, and $1,780, respectively. Probabilistic sensitivity analyses based on 5,000 simulations show that the average net present value per person remains positive: $1,894±$7,619, $27,925±$12,407, and $17,229±$24,637 in Ukraine, Belarus, and Kazakhstan, respectively. Financing IVF may represent a good investment in terms of governmental financial returns, even in lower-income countries with state-financed health care systems such as Ukraine, Belarus, and Kazakhstan.
    ClinicoEconomics and Outcomes Research 06/2015; 7:347—356. DOI:10.2147/CEOR.S79513
  • [Show abstract] [Hide abstract]
    ABSTRACT: The study aimed to determine the room for improvement of a perfect cerebrospinal fluid (CSF) biomarker and the societal incremental net monetary benefit of CSF in subjects with mild cognitive impairment (MCI) assuming a hypothetical disease-modifying Alzheimer's disease (AD) treatment. A decision model compared current practice to a perfect biomarker and to two strategies positioning CSF as add-on test when current practice concluded the presence or absence of AD. The simulated MCI population was aged on average 68.3% and 49% had AD. The room for improvement by the perfect CSF test was 0.39 quality adjusted life years, €33,622 ($43,372) savings, 2.0 potential beneficial treatment years, and 1.3-year delay in dementia conversion. The results indicated more potential benefit from a biomarker positioned to verify subjects who are not expected to have AD (i.e., to prevent undertreatment) rather than to verify subjects expected to have AD (prevent overtreatment). Sensitivity analyses explored different CSF positions. Copyright © 2015 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
    Alzheimer's & dementia: the journal of the Alzheimer's Association 06/2015; 11(8). DOI:10.1016/j.jalz.2015.02.009 · 12.41 Impact Factor
  • Source
    Ties Hoomans · Johan L Severens ·
    [Show abstract] [Hide abstract]
    ABSTRACT: Economic evaluations can inform decisions about the efficiency and allocation of resources to implementation strategies¿strategies explicitly designed to inform care providers and patients about the best available research evidence and to enhance its use in their practices. These strategies are increasingly popular in health care, especially in light of growing concerns about quality of care and limits on resources. But such concerns have hardly motivated health authorities and other decision-makers to spend on some form of economic evaluation in their assessments of implementation strategies. This editorial addresses the importance of economic evaluation in the context of implementation science¿particularly, how these analyses can be most efficiently incorporated into decision-making processes about implementation strategies.
    Implementation Science 12/2014; 9(1):168. DOI:10.1186/s13012-014-0168-y · 4.12 Impact Factor
  • Source
    Saskia Knies · Annelies Boonen · Johan L Severens ·
    [Show abstract] [Hide abstract]
    ABSTRACT: The question of how to value lost productivity in economic evaluations has been subject of debate in the past twenty years. According to the Washington panel, lost productivity influences health-related quality of life and should thus be considered a health effect instead of a cost to avoid double counting. Current empirical evidence on the inclusion of income loss when valuing health states is not decisive. We examined the relationship between three aspects of lost productivity (work-status, absenteeism and presenteeism) and patient or social valuation of health-related quality of life (HRQoL). Cross-sectional survey data were collected from a total of 830 respondents with a rheumatic disorder from four West-European countries. Health-related quality of life was expressed in either the European societal utility using EQ-5D-3L or the patient valuation using EQ-VAS. The impact of work-status (four categories), absenteeism (absent from paid work during the past three months), and presenteeism (QQ method) on EQ-5D utilities and VAS scores was examined in linear regression analyses taking into account demographic characteristics and disease severity (duration, pain and restriction). The relationship between work-status, absenteeism or presenteeism and HRQoL was stronger for patient valuation than societal valuation. Compared to work-status and presenteeism the relationship between absenteeism and HRQoL was even less explicit. However, results for all measures of lost productivity are only marginally significant and negligible compared to the influence of disease-related restrictions. This survey study in patients with a rheumatic disorder in four European countries, does not fully support the Washington panel's claim that lost productivity is a significantly related with HRQoL, and this is even more apparent for absenteeism than for work-status and presenteeism. For West-European countries, there is no reason, to include absenteeism in the QALY. Findings need to be confirmed in other disease areas.
    Cost Effectiveness and Resource Allocation 11/2014; 12(7):24. DOI:10.1186/1478-7547-12-24 · 0.87 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background In the absence of a gold standard, a panel of experts can be invited to assign a reference diagnosis for use in research. Available literature offers limited guidance on assembling and working with an expert panel for this purpose. We aimed to develop a protocol for an expert panel consensus diagnosis and evaluated its applicability in a pilot project.Methods An adjusted Delphi method was used, which started with the assessment of clinical vignettes by 3 experts individually, followed by a consensus discussion meeting to solve diagnostic discrepancies. A panel facilitator ensured that all experts were able to express their views, and encouraged the use of argumentation to arrive at a specific diagnosis, until consensus was reached by all experts. Eleven vignettes of patients suspected of having a primary neurodegenerative disease were presented to the experts. Clinical information was provided stepwise and included medical history, neurological, physical and cognitive function, brain MRI scan, and follow-up assessments over 2 years. After the consensus discussion meeting, the procedure was evaluated by the experts.ResultsThe average degree of consensus for the reference diagnosis increased from 52% after individual assessment of the vignettes to 94% after the consensus discussion meeting. Average confidence in the diagnosis after individual assessment was 85%. This did not increase after the consensus discussion meeting. The process evaluation led to several recommendations for improvement of the protocol.ConclusionA protocol for attaining a reference diagnosis based on expert panel consensus was shown feasible in research practice.
    BMC Neurology 10/2014; 14(1):190. DOI:10.1186/PREACCEPT-1702688938102976 · 2.04 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Aim: The objective of this study was to explore the cost-effectiveness of D-dimer biomarker and the societal value (headroom) of a hypothetical perfect biomarker for risk assessment and subsequent treatment stratification of prophylactic treatment for peripheral arterial disease (PAD). Patients & methods: Decision analytic modeling. Results: Use of the D-dimer biomarker to prescribe oral anticoagulants in the high-risk subset of patients is a cost-effective healthcare intervention. The headroom (societal willingness to pay multiplied by incremental quality-adjusted life years) available for the hypothetical perfect biomarker amounted to €83,877. Conclusion: D-dimer-based PAD risk assessment and treatment tailoring is cost effective. Identification of high-risk PAD patients and prescription of oral anticoagulants could potentially save substantial costs and improve chances of survival for high-risk PAD patients. However, further research of risk stratifying biomarkers test accuracy is needed to support and strengthen the results of this modeling study.
    Biomarkers in Medicine 08/2014; 8(8-8):989-999. DOI:10.2217/bmm.14.45 · 2.65 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective To use contingent valuation (CV) to derive individual consumer values for both health and broader benefits of a public-health intervention directed at lifestyle behaviour change (LBC) and to examine the feasibility and validity of the method.Method Participants of a lifestyle intervention trial (n = 515) were invited to complete an online CV survey. Respondents (n = 312) expressed willingness to invest money and time for changes in life expectancy, health-related quality of life (HRQOL) and broader quality of life aspects. Internal validity was tested for by exploring associations between explanatory variables (i.e. income, paid work, experience and risk factors for cardiovascular diseases) and willingness to invest, and by examining ordering effects and respondents' sensitivity to the scope of the benefits.ResultsThe majority of respondents (94.3%) attached value to benefits of LBC, and 87.4% were willing to invest both money and time. Respondents were willing to invest more for improvements in HRQOL (€42/month; 3 h/week) and broader quality of life aspects (€40/month; 2.6 h/week) than for improvements in life expectancy (€24/month; 2 h/week). Protest answers were limited (3%) and findings regarding internal validity were mixed.Conclusion The importance of broader quality of life outcomes to consumers suggests that these outcomes are relevant to be considered in the decision making. Our research showed that CV is a feasible method to value both health and broader outcomes of LBC, but generalizability to other areas of public health still needs to be examined. Mixed evidence regarding internal validity pleads for caution to use CV as only the base for decision making.
    Health expectations: an international journal of public participation in health care and health policy 08/2014; DOI:10.1111/hex.12195 · 3.41 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objectives Many national colorectal cancer screening campaigns have a similar structure. First, individuals are invited to take a noninvasive screening test, and, second, in the case of a positive screening test result, they are advised to undergo a more invasive follow-up test. The objective of this study was to investigate how much individuals’ participation decision in noninvasive screening is affected by the presence or absence of detailed information about invasive follow-up testing and how this effect varies over screening tests. Methods We used a labeled discrete choice experiment of three noninvasive colorectal cancer screening types with two versions that did or did not present respondents with detailed information about the possible invasive follow-up test (i.e., colonoscopy) and its procedure. We used data from 631 Dutch respondents aged 55 to 75 years. Each respondent received only one of the two versions (N = 310 for the invasive follow-up test information specification version, and N = 321 for the no-information specification version). Results Mixed logit model results show that detailed information about the invasive follow-up test negatively affects screening participation decisions. This effect can be explained mainly by a decrease in choice shares for the most preferred screening test (a combined stool and blood sample test). Choice share simulations based on the discrete choice experiment indicated that presenting invasive follow-up test information decreases screening participation by 4.79%. Conclusions Detailed information about the invasive follow-up test has a negative effect on individuals’ screening participation decisions in noninvasive colorectal cancer screening campaigns. This result poses new challenges for policymakers who aim not only to increase uptake but also to provide full disclosure to potential screening participants.
    Value in Health 07/2014; 17(5). DOI:10.1016/j.jval.2014.04.007 · 3.28 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Management of rheumatoid arthritis (RA) is characterised by a sequence of disease-modifying antirheumatic drugs (DMARDs) and biological response modifiers (BRMs). In most of the Western countries, the drug sequences are determined based on disease activity and treatment history of the patients. A model for realistic patient outcomes should reflect the treatment pathways relevant for patients with specific characteristics.
    PharmacoEconomics 06/2014; 32(10). DOI:10.1007/s40273-014-0184-4 · 2.45 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: General recommendations for a reference case for economic studies in rheumatic diseases were published in 2002 in an initiative to improve the comparability of cost-effectiveness studies in the field. Since then, economic evaluations in osteoarthritis (OA) continue to show considerable heterogeneity in methodological approach.
    Seminars in Arthritis and Rheumatism 06/2014; 44(3). DOI:10.1016/j.semarthrit.2014.06.005 · 3.93 Impact Factor

Publication Stats

3k Citations
557.35 Total Impact Points


  • 2010-2015
    • Erasmus Universiteit Rotterdam
      • • Institute of Health Policy & Management (iBMG)
      • • Institute for Medical Technology Assessment (iMTA)
      Rotterdam, South Holland, Netherlands
  • 2013
    • Utrecht University
      • Department of Pharmaceutical Sciences
      Utrecht, Utrecht, Netherlands
  • 2003-2013
    • Maastricht University
      • • CAPHRI School for Public Health and Primary Care
      • • Faculty of Health, Medicine and Life Sciences
      • • Department of General Practice
      Maestricht, Limburg, Netherlands
  • 2005-2010
    • Maastricht Universitair Medisch Centrum
      • Central Diagnostic Laboratory
      Maestricht, Limburg, Netherlands
  • 2001-2002
    • Radboud University Medical Centre (Radboudumc)
      • Department of Human Genetics
      Nymegen, Gelderland, Netherlands
  • 1998-2000
    • Radboud University Nijmegen
      • • Department of Gastroenterology and Hepatology
      • • Department of Orthodontics
      Nymegen, Gelderland, Netherlands