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van der Vorm A.,IQ healthcare | van der Laan A.L.,IQ healthcare | Borm G.,Biostatistics and Health Technology Assessment | Vernooij-Dassen M.,Healthcare Alzheimer Center Nijmegen | And 3 more authors.
Clinical Genetics | Year: 2010

Most publications on the ethical aspects of genetic research into Alzheimer's Disease (AD) concentrate on the differences between the opinions of professionals and non-professionals. Differences in rating of morally relevant issues between groups of professionals have not yet been described. A modified Delphi study in two rounds was held to identify differences between groups of experts (i.e. clinicians, representatives of patient organisations, ethicists and persons with a commercial background). The strongest correlation was found between the opinions of ethicists and representatives of patient organisations (0.67) and between clinicians and ethicists (0.62). Moderate correlation (0.55) was found between the opinions of clinicians and representatives of patient organisations. Persons with a commercial background showed a weak correlation with clinicians (0.41), ethicists (0.35) and representatives of patient organisations (0.30). These differences in rating of morally relevant issues between various professional groups are relevant for clinical practice and dementia care, particularly the different rating of prenatal diagnosis found between clinicians and representatives of patient organisations. Interdisciplinary consultations between various professional groups -including at least researchers, clinicians and ethicists -are recommended to guarantee that all considerations will be incorporated into the debate on ethical issues of genetic research into AD. © 2009 John Wiley & Sons A/S.

Van Altena A.M.,Radboud University Nijmegen | Geels Y.P.,Radboud University Nijmegen | Kiemeney L.A.L.M.,Biostatistics and Health Technology Assessment | Kiemeney L.A.L.M.,Radboud University Nijmegen | And 3 more authors.
International Journal of Gynecological Pathology | Year: 2012

Patients with double primary cancer (DPC) of the ovary and endometrium are considered to have a better prognosis than patients with only epithelial ovarian cancer (EOC). The aim of this study was to clarify the difference in prognosis by comparing clinicopathologic characteristics and survival. From the population-based database of the nationwide Netherlands Cancer Registry, women diagnosed between 1996 and 2006 with EOC were identified. Within this database of all EOC patients in 11 hospitals, the DPC patients were identified. Differences in characteristics between EOC-only and DPC patients were tested using Pearson χ 2 tests and t-tests. Differences in overall survival were analyzed by Kaplan-Meier survival analyses and log-rank tests. Multivariable Cox regression analyses were performed to study the factors that influence survival. Among 1105 EOC patients, 29 (2.6%) DPC patients were identified. DPC patients were more often premenopausal (P<0.01), in the early stage of disease (P<0.01), and more often had low-grade endometrioid tumors. Overall survival was better for DPC patients (P=0.004), but after stratification for stage the overall survival was similar. In multivariable analysis, DPC patients did not show a favorable prognosis after adjustment for age, disease stage, histology, tumor grade, and residual tumor after surgery. DPC patients seem to constitute a prognostically favorable group among EOC patients; however, after correction for age, stage, histology, tumor grade, and residue, survival is similar. This study shows how important it is for clinicians to distinguish DPC from metastatic diseases. © 2012 International Society of Gynecological Pathologists.

Ruiter D.,Radboud University Nijmegen | Cerroni L.,Medical University of Graz | Donders R.,Biostatistics and Health Technology Assessment | Kutzner H.,Dermatopathologisches Gemeinschaftslabor | And 4 more authors.
American Journal of Dermatopathology | Year: 2012

A detailed analysis of the results of the international annual International Committee for Dermatopathology-Union Européene des Médecins Specialistes dermatopathology examination was undertaken to identify clues for further improvement. The analysis covered 5 consecutive years (2006-2010) and involved a total of 860 questions (591 common questions and 269 uncommon questions) and 181 participants. It focused on the overall performance of the participants, the performance per part of the examination (theoretical or practical), the performance per format of question (multiple choice or open), the performance per dermatopathological topic, and the performance per professional background (dermatologist or pathologist). The overall performance of the participants was high (on average 75% correct answers in 2006 and 85% correct answers in the subsequent years). In the theoretical part of the examination, the topics of vascular diseases and lichenoid dermatoses scored better than the average of all topics, and the topics of cutaneous lymphoproliferative diseases and melanocytic disorders scored worse. In the first practical part (interpretation of images), dermatologists outperformed pathologists, especially on providing a diagnosis (open question format) of clinical images. In the second practical part (microscopical examination), the topics of vascular diseases, granulomatous diseases, including necrobiotic and degenerative and metabolic diseases scored better than the average of all topics, and the topic of infectious diseases scored worse. The results of this detailed analysis provide an excellent feedback to the examination committee that will be used to consider the adjustment of parts and/or topics of the examination that showed a deviant performance by the participants. In addition, it is recommended to give more attention to the postgraduate education of certain dermatopathological topics, including cutaneous lymphoproliferative diseases, melanocytic disorders, and infectious diseases. © 2012 by Lippincott Williams & Wilkins.

Kiemeney L.A.,Biostatistics and Health Technology Assessment | Kiemeney L.A.,Radboud University Nijmegen | Kiemeney L.A.,Comprehensive Cancer Center East | Sulem P.,DeCODE Genetics Inc. | And 80 more authors.
Nature Genetics | Year: 2010

Previously, we reported germline DNA variants associated with risk of urinary bladder cancer (UBC) in Dutch and Icelandic subjects. Here we expanded the Icelandic sample set and tested the top 20 markers from the combined analysis in several European case-control sample sets, with a total of 4,739 cases and 45,549 controls. The T allele of rs798766 on 4p16.3 was found to associate with UBC (odds ratio = 1.24, P = 9.9 × 10 12). rs798766 is located in an intron of TACC3, 70 kb from FGFR3, which often harbors activating somatic mutations in low-grade, noninvasive UBC. Notably, rs798766[T] shows stronger association with low-grade and low-stage UBC than with more aggressive forms of the disease and is associated with higher risk of recurrence in low-grade stage Ta tumors. The frequency of rs798766[T] is higher in Ta tumors that carry an activating mutation in FGFR3 than in Ta tumors with wild-type FGFR3. Our results show a link between germline variants, somatic mutations of FGFR3 and risk of UBC. © 2010 Nature America, Inc. All rights reserved.

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