Biology‐Driven Gene‐Gene Interaction Analysis of Age‐Related Cataract in the eMERGE Network

Bioinformatics approaches to examine gene‐gene models provide a means to discover interactions between multiple genes that underlie complex disease. Extensive computational demands and adjusting for multiple testing make uncovering genetic interactions a challenge. Here, we address these issues using our knowledge‐driven filtering method, Biofilter, to identify putative single nucleotide polymorphism (SNP) interaction models for cataract susceptibility, thereby reducing the number of models for analysis. Models were evaluated in 3,377 European Americans (1,185 controls, 2,192 cases) from the Marshfield Clinic, a study site of the Electronic Medical Records and Genomics (eMERGE) Network, using logistic regression. All statistically significant models from the Marshfield Clinic were then evaluated in an independent dataset of 4,311 individuals (742 controls, 3,569 cases), using independent samples from additional study sites in the eMERGE Network: Mayo Clinic, Group Health/University of Washington, Vanderbilt University Medical Center, and Geisinger Health System. Eighty‐three SNP‐SNP models replicated in the independent dataset at likelihood ratio test P < 0.05. Among the most significant replicating models was rs12597188 (intron of CDH1)–rs11564445 (intron of CTNNB1). These genes are known to be involved in processes that include: cell‐to‐cell adhesion signaling, cell‐cell junction organization, and cell‐cell communication. Further Biofilter analysis of all replicating models revealed a number of common functions among the genes harboring the 83 replicating SNP‐SNP models, which included signal transduction and PI3K‐Akt signaling pathway. These findings demonstrate the utility of Biofilter as a biology‐driven method, applicable for any genome‐wide association study dataset.     

An In‐House Prevocational Training Program for Newly Discharged Psychiatric Inpatients: Exploring Its Employment Outcomes and the Predictive Factors

Individuals with severe mental disorders continue to experience low employment rates. Occupational therapists play an important role in helping these individuals develop the skills and obtain the supports necessary for productive living. This retrospective cohort study aimed to explore employment outcomes and identify factors predictive of the outcomes of an in‐house prevocational training program designed for newly discharged psychiatric inpatients. Data retrieved from the files of 58 participants including demographics, diagnostic history, physical fitness, functional assessment results, the use of vocational counselling service and employment status were analyzed. The overall employment rates among the participants were high (67.2–79.3%) within the 6 months following the prevocational training program. No significant differences were found in the employment rates across the 1, 3 and 6‐month time periods post‐training. Vocational counselling service post‐training and hand function were two factors predictive of participants' employment outcomes. Occupational therapists should attend to the clients' need for continuous vocational support and carefully identify the personal, functional and environmental factors contributing to successful employment. Caution in interpreting the results is warranted because of the lack of control and randomization in this retrospective study. Additional longitudinal cohort or experimental studies would add further certainty to the current findings. Copyright © 2015 John Wiley & Sons, Ltd.     

The Return of Actionable Variants Empirical (RAVE) Study,a Mayo Clinic Genomic Medicine Implementation Study: Design and Initial Results

Objectives

To identify clinically actionable genetic variants from targeted sequencing of 68 disease-related genes, estimate their penetrance, and assess the impact of disclosing results to participants and providers.

Anesthesia for subcutaneous implantable cardioverter‐defibrillator implantation: Perspectives from the clinical experience of a U.S. panel of physicians

1 Background and objective

Worldwide adoption of the subcutaneous implantable cardioverter‐defibrillator (S‐ICD) for preventing sudden cardiac death continues to increase, as longer‐term evidence demonstrating the safety and efficacy of the S‐ICD expands. As a relatively new technology, comprehensive anesthesia guidance for the management of patients undergoing S‐ICD placement is lacking. This article presents advantages and disadvantages of different periprocedural sedation and anesthesia options for S‐ICD implants including general anesthesia, monitored anesthesia care, regional anesthesia, and nonanesthesia personnel administered sedation and analgesia.

2 Methods

Guidance, for approaches to anesthesia care during S‐ICD implantation, is presented based upon literature review and consensus of a panel of high‐volume S‐ICD implanters, a regional anesthesiologist, and a cardiothoracic anesthesiologist with significant S‐ICD experience. The panel developed suggested actions for perioperative sedation, anesthesia, surgical practices, and a decision algorithm for S‐ICD implantation.

3 Conclusions

While S‐ICD implantation currently requires higher sedation than transvenous ICD systems, the panel consensus is that general anesthesia is not required or is obligatory for the majority of patients for the experienced S‐ICD implanter. The focus of the implanting physician and the anesthesia services should be to maximize patient comfort and take into consideration patient‐specific comorbidities, with a low threshold to consult the anesthesiology team.     

Relative Oral Bioavailability of an Abuse-deterrent,Extended-release Formulation of Morphine Versus Extended-release Morphine: A 2-period,Single-dose,Randomized Crossover Study in Healthy Subjects

Purpose

Morphine ARER is a novel oral, abuse-deterrent, extended-release (ER) formulation of morphine sulfate with physical and chemical properties that deter misuse and abuse by nonoral routes of administration. Here we evaluate the relative bioavailability of morphine ARER and extended-release morphine.