Showing papers by "George Luta published in 2010"

Randomized Controlled Trial of a Psychosocial Telephone Counseling Intervention in BRCA1 and BRCA2 Mutation Carriers

Abstract: Background: Responses following BRCA1/2 genetic testing are relevant for the comprehension of risk status and may play a role in risk management decision making. The objective of this study was to evaluate a psychosocial telephone counseling (PTC) intervention delivered to BRCA1/2 mutation carriers following standard genetic counseling (SGC). We examined the effect of the intervention on distress and the concerns related to genetic testing. Methods: This prospective randomized clinical trial included 90 BRCA1/2 mutation carriers. We measured anxiety, depression, and genetic testing distress outcomes at intervention baseline and 6 and 12 months following disclosure. We evaluated the effects of SGC versus SGC plus PTC on psychological outcomes using intention-to-treat analyses through generalized estimating equations. Results: At 6 months, PTC reduced depressive symptoms ( Z = −2.25, P = 0.02) and genetic testing distress ( Z = 2.18, P = 0.02) compared with SGC. Furthermore, women in the intervention condition reported less clinically significant anxiety at 6 months (χ21 = 4.11, P = 0.04) than women who received SGC. We found no differences in outcomes between the intervention groups at the 12-month follow-up. Conclusions: As an adjunct to SGC, PTC delivered following disclosure of positive BRCA1/2 test results seems to offer modest short-term benefits for distress and anxiety. These results build upon a growing literature of psychosocial interventions for BRCA1/2 carriers and, given the potential impact of affect on risk management decision making, suggest that some carriers may derive benefits from adjuncts to traditional genetic counseling. Cancer Epidemiol Biomarkers Prev; 19(3); 648–54

The curvHDR method for gating flow cytometry samples

Abstract: Background: High-throughput flow cytometry experiments produce hundreds of large multivariate samples of cellular characteristics. These samples require specialized processing to obtain clinically meaningful measurements. A major component of this processing is a form of cell subsetting known as gating. Manual gating is timeconsuming and subjective. Good automatic and semi-automatic gating algorithms are very beneficial to highthroughput flow cytometry. Results: We develop a statistical procedure, named curvHDR, for automatic and semi-automatic gating. The method combines the notions of significant high negative curvature regions and highest density regions and has the ability to adapt well to human-perceived gates. The underlying principles apply to dimension of arbitrary size, although we focus on dimensions up to three. Accompanying software, compatible with contemporary flow cytometry infor-matics, is developed. Conclusion: The method is seen to adapt well to nuances in the data and, to a reasonable extent, match human perception of useful gates. It offers big savings in human labour when processing high-throughput flow cytometry data whilst retaining a good degree of efficacy.

A new point containment test algorithm based on preprocessing and determining triangles

Abstract: In this paper, we revisit the point-in-polyhedron problem. After reviewing previous work, we develop further insight into the problem. We then claim that, for a given testing point and a three-dimensional polyhedron, a single determining triangle can be found which suffices to determine whether the point is inside or outside the polyhedron. This work can be considered to be an extension and implementation of Horn's work, which inspired us to propose a theorem for obtaining determining triangles. Building upon this theorem, algorithms are then presented, implemented, and tested. The results show that although our code has the same asymptotic time efficiency as commonly used octree-based ray crossing methods, in practice it is usually several times and sometimes more than ten times faster, while other costs such as preprocessing time and memory requirements remain the same. The ideas proposed in this paper are simple and general. They thus extend naturally to multi-material models, i.e., polyhedrons subdivided into smaller regions by internal boundaries.

Primary care providers’ willingness to recommend BRCA1/2 testing to adolescents

Abstract: Clinical practice guidelines discourage pediatric genetic testing for BRCA1/2 mutations due to a lack of timely medical benefit and psychosocial risk. Yet, some high risk families approach primary care providers (PCPs) about testing adolescents, and little is known about PCPs attitudes regarding these requests. We assessed recommendations for testing to a composite patient (a healthy 13-year-old female, mother is a BRCA mutation carrier) among 161 adolescent and family PCPs attending a national medical conference. Testing recommendations were measured with a multidimensional scale that assessed perspectives on informed consent, genetic counseling, and insurance coverage. PCPs expressed moderate willingness to recommend testing; surprisingly, 31% recommended adolescent testing “unconditionally.” In multivariable regression modeling, recommendation was positively associated with higher clinical practice volume (P < .05) and greater frequency of ordering other pediatric genetic tests (P < .01). Despite a decade of clinical practice guideline advice to the contrary, experienced PCPs may still be inclined to recommend BRCA1/2 genetic testing to adolescents from high risk families. When paired with emerging data on the relative safety and efficacy of breast cancer genetic testing for high risk women and the advent of direct-to-consumer marketing of BRCA1/2 cancer genetic tests, professional societies may need to explore best practices to counsel high risk families and their PCPs about the potential risks and benefits of pediatric BRCA1/2 testing.

Likelihood inference for a two-stage design with treatment selection.

Abstract: A conditional likelihood-based approach is proposed to construct confidence intervals for the parameters of interest in a two-stage design with treatment selection after the first stage. Both a Wald confidence interval and a confidence interval based on inverting the likelihood ratio test are proposed. The operating characteristics of these confidence intervals: the coverage probabilities and average confidence interval lengths, as well as the average bias and mean-square error of the corresponding point estimates, compare favorably with other available techniques. Possible extensions and an alternative unconditional approach based on the likelihood with missing at random mechanism are also briefly described.