Theoretical potential for endometrial cancer prevention through primary risk factor modification: Estimates from the EPIC cohort

Endometrial cancer (EC) incidence rates vary ~10-fold worldwide, in part due to variation in EC risk factor profiles. Using an EC risk model previously developed in the European EPIC cohort, we evaluated the prevention potential of modified EC risk factor patterns and whether differences in EC incidence between a European population and low-risk countries can be explained by differences in these patterns. Predicted EC incidence rates were estimated over 10 years of follow-up for the cohort before and after modifying risk factor profiles. Risk factors considered were: body mass index (BMI, kg/m²), use of postmenopausal hormone therapy (HT) and oral contraceptives (OC) (potentially modifiable); and, parity, ages at first birth, menarche and menopause (environmentally conditioned, but not readily modifiable). Modeled alterations in BMI (to all ≤23 kg/m²) and HT use (to all non-HT users) profiles resulted in a 30% reduction in predicted EC incidence rates; individually, longer duration of OC use (to all ≥10 years) resulted in a 42.5% reduction. Modeled changes in not readily modifiable exposures (i.e., those not contributing to prevention potential) resulted in ≤24.6% reduction in predicted EC incidence. Women in the lowest decile of a risk score based on the evaluated exposures had risk similar to a low risk countries; however, this was driven by relatively long use of OCs (median = 23 years). Our findings support avoidance of overweight BMI and of HT use as prevention strategies for EC in a European population; OC use must be considered in the context of benefits and risks.     

Powerful rare variant association testing in a copula-based joint analysis of multiple phenotypes

In genetic association studies of rare variants, the low power of association tests is one of the main challenges. In this study, we propose a new single-marker association test called C-JAMP (Copula-based Joint Analysis of Multiple Phenotypes), which is based on a joint model of multiple phenotypes given genetic markers and other covariates. We evaluated its performance and compared its empirical type I error and power with existing univariate and multivariate single-marker and multi-marker rare-variant tests in extensive simulation studies. C-JAMP yielded unbiased genetic effect estimates and valid type I errors with an adjusted test statistic. When strongly dependent traits were jointly analyzed, C-JAMP had the highest power in all scenarios except when a high percentage of variants were causal with moderate/small effect sizes. When traits with weak or moderate dependence were analyzed, whether C-JAMP or competing approaches had higher power depended on the effect size. When C-JAMP was applied with a misspecified copula function, it still achieved high power in some of the scenarios considered. In a real-data application, we analyzed sequencing data using C-JAMP and performed the first genome-wide association studies of high-molecular-weight and medium-molecular-weight adiponectin plasma concentrations. C-JAMP identified 20 rare variants with p-values smaller than 10⁻⁵, while all other tests resulted in the identification of fewer variants with higher p-values. In summary, the results indicate that C-JAMP is a powerful, flexible, and robust method for association studies, and we identified novel candidate markers for adiponectin. C-JAMP is implemented as an R package and freely available from https://cran.r-project.org/package=CJAMP .     

Wie häufig werden Patienten mit depressiven Störungen in der hausärztlichen Praxis erkannt?

Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz - Hausärzte sind als Primärversorger für Patienten mit depressiven Störungen entscheidende Weichensteller...     

PBL core skills faculty development workshop 1: An experiential exercise with the PBL process

This report describes the first in a series of foundation-building faculty development workshops focused on the instructional methodology of problem-based learning (PBL). The PBL Process workshop reported here introduced the learning theory topics supporting PBL and utilized an extended roleplay method to provide participants with personal experience with the PBL learning cycle. Overall, participants were satisfied with the methods and content of the workshop. A majority of survey respondents indicated that simulating a complete iteration of the PBL process was an effective way to learn about PBL. Participants expressed relatively greater difficulty understanding and performing activities related to qualitative assessment of learning processes. The workshop was developed to align with adult learning principles, and continued refinement of the workshop has enhanced the learning theory components underpinning PBL as well as the experiential aspects. These dual goals have resulted in blending the existing experiential workshop with an online distance-learning component addressing the learning theory topics relevant to PBL pedagogy.     

In-vitro assessment of a registration protocol for image guided implant dentistry

In this study a computer aided navigation technique for accurate positioning of oral implants was assessed. An optical tracking system with specially designed tools for monitoring the position of surgical instruments relative to the patient was used to register 5 partially or completely edentulous jaw models. Besides the accuracy of the tracking system, the precision of localizing a specific position on 3-dimensional preoperative imagery is governed by the registration algorithm which conveys the coordinate system of the preoperative computed tomography (CT) scan to the actual patient position. Two different point-to-point registration algorithms were compared for their suitability for this application. The accuracy was determined separately for the localization error of the position measurement hardware (fiducial localization error-FLE) and the error as reported by the registration algorithm (fiducial registration error-FRE). The overall error of the navigation procedure was determined as the localization error of additional landmarks (steel spheres, 0.5 mm diameter) after registration (target registration error-TRE). Images of the jaw models were obtained using a high resolution CT scan (1.5 mm slice thickness, 1 mm table feed, incremental scanning, 120 kV, 150 mAs, 512 x 512 matrix, FOV 120 mm). The accuracy of the position measurement probes was 0.69 +/- 0.15 mm (FLE). Using 3 implanted fiducial markers, FRE was 0.71 +/- 0.12 mm on average and 1.00 +/- 0.13 mm maximum. TRE was found to be 1.23 +/- 0.28 mm average and 1.87 +/- 0.47 mm maximum. Increasing the number of fiducial markers to a total of 5 did not significantly improve precision. Furthermore it was found that a registration algorithm based on solving an eigenvalue problem is the superior approach for point-to-point matching in terms of mathematical stability. The experimental results indicate that positioning accuracy of oral implants may benefit from computer aided intraoperative navigation. The accuracy achieved compares well to the resolution of the CT scan used. Further development of point-to-point/point-to-surface registration methods and tracking hardware has the potential to improve the precision of the method even further. Our system has potential to reduce the intraoperative risk of causing damage to critical anatomic structures, to minimize the efforts in prosthetic modelling, and to simplify the task of transferring preoperative planning data precisely to the operating room in general.     

Evaluation of accuracy of computer-aided intraoperative positioning of endosseous oral implants in the edentulous mandible

The overall accuracy of a novel surgical computer-aided navigation system for placement of endosseous implants was evaluated. Five dry cadaver mandibles were scanned using high resolution computed tomography (HRCT). The position of four interforaminal dental implants was planned on the computer screen and transferred to the cadaver mandibles using VISIT, a surgical navigation software developed at the Vienna General Hospital. The specimens were HRCT-scanned again to compare the position of the implants with the preoperative plan on reformatted slices after matching of the pre- and postoperative data sets using the mutual information technique. The overall accuracy was 0.96 +/- 0.72 mm (range 0.0-3.5 mm). No perforation of the mandibular cortex or damage to the mandibular canal occurred. We conclude that computer-aided implant surgery can reach a level of accuracy where further clinical developments are feasible.