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Koch L.,German Cancer Research Center | Bertram H.,Cancer Registry of North Rhine Westphalia Munster Region | Eberle A.,Leibniz Institute for Prevention Research and Epidemiology | Holleczek B.,Saarland Cancer Registry | And 5 more authors.
Psycho-Oncology | Year: 2014

Background Fear of recurrence (FoR) is a widespread problem among breast cancer survivors. So far, little is known about prevalence, determinants, and consequences of FoR specifically in long-term breast cancer survivors, even though it was found to be one of the most important concerns in this group. Methods Analyses are based on data of several population-based cohorts of long-term breast cancer survivors, recruited by six German cancer registries. Overall, 2671 women were included in the analyses. FoR was assessed using the short form of the Fear of Progression Questionnaire. Potential determinants of moderate/high FoR and the association with depression and quality of life (QoL) were explored via multiple logistic and linear regression. Results Even though the majority of women reported low levels of FoR (82%), a substantial percentage experienced moderate (11%) and high (6%) FoR. Younger age (odds ratio=3.00, confidence intervals=1.91-4.73 for women below age 55years) and considering oneself as a tumor patient (odds ratio=3.36, confidence intervals=2.66-4.25) were found to exhibit the strongest associations with moderate/high FoR. Overall, psychosocial and sociodemographic factors played a far bigger role in FoR than clinical factors. Higher FoR was associated with higher depression and lower QoL. Conclusion Fear of recurrence (mostly low levels) is highly prevalent among long-term breast cancer survivors and can negatively affect QoL and well-being. Therefore, it should be given appropriate consideration in research and clinical practice. As specifically younger women tended to be impacted by FoR, it is crucial to be particularly attentive to specific needs of younger survivors. Copyright © 2013 John Wiley & Sons, Ltd. Copyright © 2013 John Wiley & Sons, Ltd.

Huemer M.,Charite - Medical University of Berlin | Sarganas G.,Charite - Medical University of Berlin | Bronder E.,Charite - Medical University of Berlin | Klimpel A.,Charite - Medical University of Berlin | And 3 more authors.
Pharmacotherapy | Year: 2015

Dronedarone is a promising, relatively new antiarrhythmic agent characterized by structural similarities to amiodarone but without amiodarone's severe organ toxicity. The proarrhythmic potential of dronedarone, however, is of increasing concern. We describe a 76-year-old woman who had been receiving dronedarone 400 mg twice/day to prevent recurrent atrial tachycardia with rapid ventricular response. Several months later, she came to the emergency department with decompensated congestive heart failure and episodes of atrial tachycardia; digoxin 0.5 mg and furosemide 40 mg were administered intravenously. Thereafter nonsustained torsade de pointes (TdP) tachycardia occurred. She was transferred to the intensive care unit where a dose of amiodarone 150 mg was administered intravenously by mistake. Thereafter, the patient showed sustained TdP necessitating cardiac resuscitation. Dronedarone was discontinued, and digoxin and amiodarone were not administered again. Under dronedarone a relevant QT prolongation was documented that was additionally augmented after concomitant treatment with digoxin and amiodarone. Use of the Naranjo adverse drug reaction probability scale indicated a probable adverse drug reaction to dronedarone (score of 7). To our knowledge, this is the first case report of a patient who experienced TdP tachycardias while receiving dronedarone therapy in connection with a worsening of heart failure and possible drug interactions with digoxin and amiodarone. Clinicians should be aware of this potential adverse drug reaction and perform repeated heart rate-corrected QT (QTc) interval measurements as well as screening for congestive heart failure in patients receiving dronedarone therapy. © 2015 Pharmacotherapy Publications, Inc.

Riedel O.,Leibniz Institute for Prevention Research and Epidemiology | Riedel O.,TU Dresden | Klotsche J.,Deutsches Rheumaforschungszentrum | Wittchen H.-U.,TU Dresden
Parkinsonism and Related Disorders | Year: 2014

Introduction: Clinical Global Impression of Severity (CGIS) is a common measure in clinical research on Parkinson's disease (PD). However, patient features that contribute to the impression of the physician remain unclear. In particular, the impact of cognitive impairment and depression is understudied. Methods: In a nationwide study on 1449 outpatients with PD, examined by 315 office-based neurologists, PD severity was documented with the Unified Parkinson's Disease Rating Scale (UPDRS-I, II, and IV). All patients were screened with the Montgomery-Asberg Depression Rating Scale (MADRS) for depression. The diagnosis of dementia was based on Diagnostic and Statistical Manual of Mental Disorders IV Text Revision criteria. Each patient was rated on the CGIS. Results: CGIS ratings were available for 1438 patients, of which 50.8% were rated as "borderline" to "moderately ill" and 49.2% as "markedly" to "extremely ill." Worse ratings were associated with higher age (p<0.001), longer PD duration (p<0.001), and female sex (p<0.001). The impact of patient and physician variables on CGIS rating was calculated with three regression models (A: single bivariate regression; B: multivariate regression; and C: multivariate, multilevel regression, including physician variables). In all models, higher UPDRS-II scores and longer disease duration of PD were the strongest predictors for a worse CGIS rating. In the multivariate models (B and C), neuropsychiatric symptoms were unrelated to the CGIS rating. Conclusion: The additional burden of dementia and depression was underestimated in the CGIS rating, suggesting that they are possibly relativized against the motor impairment. © 2014 Elsevier Ltd.

Stang A.,Martin Luther University of Halle Wittenberg | Stang A.,Boston University | Jansen L.,German Cancer Research Center | Trabert B.,U.S. National Institutes of Health | And 6 more authors.
Cancer Epidemiology | Year: 2013

Introduction: The aim of this study was to provide detailed age-specific (5-year age groups) and histology-specific (histologic subtypes of seminoma and nonseminoma) relative survival estimates of testicular germ cell cancer patients in Germany and the United States (U.S.) for the years 2002-2006 and to compare these estimates between countries. Methods: We pooled data from 11 cancer registries of Germany and used data from the U.S. (SEER-13 database) including 11,508 and 10,774 newly diagnosed cases (1997-2006) in Germany and the U.S., respectively. We estimated 5-year relative survival (5-year-RS) by histology and age based on period analysis. Results: 5-year-RS for testicular germ cell tumors was 96.7% and 96.3% in Germany and the U.S., respectively. 5-Year-RS for spermatocytic seminoma was close to 100% in both countries. 5-Year-RS for nonseminoma was lower than for classical seminoma in Germany (93.3% versus 97.6%) and the U.S. (91.0% versus 98.2%). Among nonseminomas, choriocarcinomas provided the lowest 5-year-RS in both countries (Germany 80.1%, U.S. 79.6%). Age-specific 5-year-RS for seminoma showed only little variation by age. 5-Year-RS for nonseminomas tended to be lower at higher ages, especially for malignant teratoma. Discussion: This is the first study that provides up-to-date survival estimates for testicular cancer by histology and age in Germany and the U.S. Survival after a diagnosis of testicular cancer is very comparable between Germany and the U.S. 5-Year-RS for spermatocytic seminoma was close to 100% and the lowest 5-year-RS occurred among choriocarcinoma. Higher age at diagnosis is associated with a poorer prognosis among nonseminoma patients. © 2013 Elsevier Ltd.

Friemel J.,University of Zurich | Friemel J.,Leibniz Institute for Prevention Research and Epidemiology | Rechsteiner M.,University of Zurich | Frick L.,University of Zurich | And 7 more authors.
Clinical Cancer Research | Year: 2015

Purpose: Morphologic intratumor heterogeneity is well known to exist in hepatocellular carcinoma (HCC), but very few systematic analyses of this phenomenon have been performed. The aim of this study was to comprehensively characterize morphologic intratumor heterogeneity in HCC. Also, taken into account were well-known immunohistochemical markers and molecular changes in liver cells that are considered in proposed classifications of liver cell neoplasms or discussed as molecular therapeutic targets. Experimental Design: In HCC of 23 patients without medical pretreatment, a total of 120 tumor areas were defined. Analyzed were cell and tissue morphology, expression of the liver cell markers cytokeratin (CK)7, CD44, α-fetoprotein (AFP), epithelial cell adhesion molecule (EpCAM), and glutamine synthetase (GS) along with mutations of TP53 and CTNNB1, assayed by both Sanger and next-generation sequencing. Results: Overall, intratumor heterogeneity was detectable in the majority of HCC cases (20 of 23, 87%). Heterogeneity solely on the level of morphology was found in 6 of 23 cases (26%), morphologic heterogeneity combined with immunohistochemical heterogeneity in 9 of 23 cases (39%), and heterogeneity with respect to morphologic, immunohistochemical, and mutational status of TP53 and CTNNB1 in 5 of 23 cases (22%). Conclusions: Our findings demonstrate that intratumor heterogeneity represents a challenge for the establishment of a robust HCC classification and may contribute to treatment failure and drug resistance in many cases of HCC. ©2014 AACR.

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