Drichel D.,German Center for Neurodegenerative Diseases |
Herold C.,German Center for Neurodegenerative Diseases |
Herold C.,Institute for Medical Biometry |
Lacour A.,German Center for Neurodegenerative Diseases |
And 6 more authors.
Human Heredity | Year: 2014
Important methodological advancements in rare variant association testing have been made recently, among them collapsing tests, kernel methods and the variable threshold (VT) technique. Typically, rare variants from a region of interest are tested for association as a group ('bin'). Rare variant studies are already routinely performed as whole-exome sequencing studies. As an alternative approach, we propose a pipeline for rare variant analysis of imputed data and develop respective quality control criteria. We provide suggestions for the choice and construction of analysis bins in whole-genome application and support the analysis with implementations of standard burden tests (COLL, CMAT) in our INTERSNP-RARE software. In addition, three rare variant regression tests (REG, FRACREG and COLLREG) are implemented. All tests are accompanied with the VT approach which optimizes the definition of 'rareness'. We integrate kernel tests as implemented in SKAT/SKAT-O into the suggested strategies. Then, we apply our analysis scheme to a genome-wide association study of Alzheimer's disease. Further, we show that our pipeline leads to valid significance testing procedures with controlled type I error rates. Strong association signals surrounding the known APOE locus demonstrate statistical power. In addition, we highlight several suggestive rare variant association findings for follow-up studies, including genomic regions overlapping MCPH1, MED18 and NOTCH3. In summary, we describe and support a straightforward and cost-efficient rare variant analysis pipeline for imputed data and demonstrate its feasibility and validity. The strategy can complement rare variant studies with next generation sequencing data. © 2014 S. Karger AG, Basel.
Hoeller T.,Institute for Medical Biometry |
Blum A.,Private Practice |
Schmid-Wendtner M.-H.,The Interdisciplinary Center
Journal of the American Academy of Dermatology | Year: 2012
Background: The sonographic examination of peripheral lymph nodes (LNs) plays an important role in the preoperative treatment and in the follow-up of patients with melanoma. Objective: A prospective study including 200 consecutive patients with a history of invasive cutaneous melanoma was performed at the Department of Dermatology and Allergy, University of Bonn, Germany, to examine the influence of sporting activity, physical workload, interferon alfa therapy, smoking habits, and infections of the upper respiratory tract on morphology and number of LNs analyzed by high-resolution ultrasound. Methods: Between May 2010 and June 2011, 106 men and 94 women (mean age 51.1 ± 12.8 years) were included in this study. During their follow-up visits for cutaneous melanoma, high-resolution ultrasound examination of cervical, axillary, and inguinal LN regions were performed. LN diameters and volumes were measured and correlated with the above given factors. Results: Sports-active patients had more LNs in inguinal regions, a higher volume and a larger LN diameter, and a higher maximum width of the hypoechoic LN margin in comparison with the nonactive patients. Patients with a hard physical workload in their occupations had a significantly higher volume of the biggest LN. Compared with nonsmoking patients smokers presented higher values in the total quantity of the LNs, in the greatest volume of LN, and in the greatest diameter of LN in the cervical regions. The other factors had no significant influence on the LN parameters. Limitations: Our study population was too small to comment on influencing factors in more detail especially the influences of different sporting activities or smoking habits. Conclusion: Sporting activity, physical workload, and smoking habits as associated cofactors influencing sonomorphologic aspects in patients with cutaneous melanoma should always be considered. © 2012 by the American Academy of Dermatology, Inc.
Rosendal C.,University of Heidelberg |
Hien M.D.,University Hospital Freiburg |
Bruckner T.,Institute for Medical Biometry |
Martin E.O.,University of Heidelberg |
And 2 more authors.
Journal of the American Society of Echocardiography | Year: 2012
Background: The impact of mitral valve surgery on left ventricular outflow tract (LVOT) dimensions is unclear. Real-time three-dimensional transesophageal echocardiography permits excellent visualization of the LVOT and might improve standard two-dimensional measurements. In this study, LVOT area and shape were assessed before and after mitral valve surgery. Methods: Thirty-five patients undergoing mitral valve repair or replacement were retrospectively included in the study and compared with 15 patients undergoing coronary artery bypass grafting. LVOT area was measured by planimetry. Maximum possible methodologic errors by assuming a circular LVOT and an eccentricity index were calculated. LVOT diameter in a midesophageal long-axis view served to calculate the error for the circular LVOT determined in common intraoperative practice. Results: Common intraoperative two-dimensional measurements underestimated actual LVOT area by 21%. Mitral valve surgery led to a significant reduction of LVOT area by 7%. Although LVOT height remained unchanged, width decreased from 2.72 to 2.53 cm (-7%), resulting in a more circular shape of the LVOT. This effect was more pronounced the smaller the size of the implanted annuloplasty ring or prosthesis. Coronary artery bypass grafting did not affect the LVOT. Left ventricular ejection fraction was significantly correlated with LVOT eccentricity. Impaired ventricular function and higher end-systolic volumes were associated with a rounder shape. Conclusions: The eccentric LVOT shape leads to a distinct underestimation of its area with two-dimensional measurements. LVOT eccentricity is less distinct in patients with low ejection fractions and higher end-systolic volumes. LVOT width is decreased through annuloplasty rings and prostheses, and the smaller the implanted device, the more profound the reduction. © 2012 by the American Society of Echocardiography.
Debald M.,University of Bonn |
Wolfgarten M.,University of Bonn |
Kreklau P.,University of Bonn |
Abramian A.,University of Bonn |
And 6 more authors.
Oncology Research and Treatment | Year: 2014
Background: The routinely practiced staging for distant metastasis in patients with primary breast cancer has been increasingly questioned. Patients and Methods: Data from 742 patients with breast cancer who had completed staging (chest x-ray, liver ultrasound, and bone scan) were retrospectively analyzed. Present findings were transferred to a dataset of a voluntarily monitored benchmarking project by the West German Breast Center that included patient data of 179 breast cancer centers. Results: Routine staging examinations revealed in 1.2% (n = 9) distant metastasis and in 38.8% (n = 288) suspicious results. In total, 15 patients (2%) had distant metastases confirmed by additional diagnostics. The existence of distant metastases correlated with tumor size, nodal state, and lymphatic vessel spread. Tumor size and nodal state were independent predictors for disseminated disease. The risk of exhibiting distant metastases was 0.77% for patients with tumor stage pT1 pN1. Based on these findings, in 159,310 patients 41,728 chest x-rays, 43,950 liver ultrasounds, and 39,037 bone scans could have been avoided. Conclusion: Asymptomatic patients with tumor stages ≤ pT1 pN1 do not benefit from staging of primary breast cancer. Suspending staging examinations for these patients could reduce cost without restricting oncologic safety. © 2014 S. Karger GmbH, Freiburg.
Meyer S.,Saarland University |
Gortner L.,Saarland University |
Larsen A.,Saarland University |
Kutschke G.,Saarland University |
And 3 more authors.
Swiss Medical Weekly | Year: 2013
Background: A high prevalence of complementary and alternative medicine (CAM) use has been documented in children with chronic illnesses. Conversely, evidencebased medicine is considered an important contributor in providing the best quality of care. METHODS: We performed a systematic overview/synthesis of all Cochrane reviews published between 1995 and 2012 in paediatrics that assessed the efficacy, and clinical implications and limitations of CAM use in children. Main outcome variables were: percentage of reviews that concluded that a certain intervention provides a benefit, percentage of reviews that concluded that a certain intervention should not be performed, and percentage of studies that concluded that the current level of evidence is inconclusive. RESULTS: A total of 135 reviews were included - most from the United Kingdom (29/135), Australia (24/135) and China (24/135). Only 5/135 (3.7%) reviews gave a recommendation in favour of a certain intervention; 26/135 (19.4%) issued a conditional positive recommendation, and 9/135 (6.6%) reviews concluded that certain interventions should not be performed. Ninety-five reviews (70.3%) were inconclusive. The proportion of inconclusive reviews increased during three, a priori-defined, time intervals (1995-2000: 15/27 [55.6%]; 2001-2006: 33/44 [75%]; and 2007-2012: 47/64 [73.4%]). The three most common criticisms of the quality of the studies included were: more research needed (82/135), low methodological quality (57/ 135) and small number of study participants (48/135). CONCLUSIONS: Given the disproportionate number of inconclusive reviews, there is an ongoing need for high quality research to assess the potential role of CAM in children. Unless the study of CAM is performed to the same science-based standards as conventional therapies, CAM therapies risk being perpetually marginalised by mainstream medicine.
Huber F.,University of Zürich |
Montani M.,University of Bern |
Sulser T.,University of Zürich |
Jaggi R.,University of Bern |
And 6 more authors.
British Journal of Cancer | Year: 2015
Background: Treatment planning of localised prostate cancer remains challenging. Besides conventional parameters, a wealth of prognostic biomarkers has been proposed so far. None of which, however, have successfully been implemented in a routine setting so far. The aim of our study was to systematically verify a set of published prognostic markers for prostate cancer. Methods: Following an in-depth PubMed search, 28 markers were selected that have been proposed as multivariate prognostic markers for primary prostate cancer. Their prognostic validity was examined in a radical prostatectomy cohort of 238 patients with a median follow-up of 60 months and biochemical progression as endpoint of the analysis. Immunohistochemical evaluation was performed using previously published cut-off values, but allowing for optimisation if necessary. Univariate and multivariate Cox regression were used to determine the prognostic value of biomarkers included in this study. Results: Despite the application of various cut-offs in the analysis, only four (14%) markers were verified as independently prognostic (AKT1, stromal AR, EZH2, and PSMA) for PSA relapse following radical prostatectomy. Conclusions: Apparently, many immunohistochemistry-based studies on prognostic markers seem to be over-optimistic. Codes of best practice, such as the REMARK guidelines, may facilitate the performance of conclusive and transparent future studies. © 2015 Cancer Research UK.
Celebi N.,University of Tübingen |
Zwirner K.,University of Tübingen |
Lischner U.,University of Tübingen |
Bauder M.,University of Tübingen |
And 6 more authors.
Ultraschall in der Medizin | Year: 2012
Purpose: Ultrasound is a widely used diagnostic tool. In medical education, it can be used to teach sonographic anatomy as well as the basics of ultrasound diagnostics. Some medical schools have begun implementing student tutor-led teaching sessions in sonographic abdominal anatomy in order to meet the growing demand in ultrasound teaching. However, while this teaching concept has proven to be feasible and well accepted, there is limited data regarding its effectiveness. We investigated whether student tutors teach sonographic anatomy as effectively as faculty staff sonographers. Materials and Methods: 50 medical students were randomly assigned to one of two groups. 46 of these could be included in the analysis. One group was taught by student tutors (ST) and the other by a faculty staff sonographer (FS). Using a pre/post-test design, students were required to locate and label 15 different abdominal structures. They printed out three pictures in three minutes and subsequently labeled the structures they were able to identify. The pictures were then rated by two blinded faculty staff sonographers. A mean difference of one point in the improvement of correctly identified abdominal structures between the pre-test and post-test among the two groups was regarded as equivalent. Results: In the pre-test, the ST (FS) correctly identified 1.6±1.0 (2.0±1.1) structures. Both the ST and FS group showed improvement in the post-test, correctly identifying 7.8±2.8 vs. 8.9±2.9 structures, respectively (p<.0001 each). Comparing the improvement of the ST (6.2±2.8 structures) versus the FS (6.9±3.2) showed equivalent results between the two groups (p<.05 testing for equivalence). Conclusion: Basic abdominal sonographic anatomy can be taught effectively by student tutors. © Georg Thieme Verlag KG Stuttgart · New York.