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Objective To study the use of CYP2C19 genotyping to guide P2Y12 inhibitor selection to maximize efficacy, and attenuate risk in appropriate patients who underwent PCI for CAD. Methods We performed a retrospective analysis of 868 patients with CAD who received CYP2C19 genotyping after PCI and changed P2Y12 inhibitor based on the results. Patients were divided into two groups based on clopidogrel metabolizer status. Group I: Intermediate (IM) and poor metabolizers (PM). Group II: Ultra-rapid (UM), rapid (RM) and normal metabolizers (NM). Each group was then categorized to one of two treatment arms guided by CYP2C19 genotype. Category 1: IM/PM started on clopidogrel, switched to ticagrelor or prasugrel; 2:IM/PM started on ticagrelor/prasugrel, continued these medications; 3: UM/RM/NM started on ticagrelor/prasugrel, switched to clopidogrel; 4: UM/RM/NM started on clopidogrel, continued clopidogrel. Death due to cardiac causes, bleeding events, non-fatal MI, target vessel revascularization (TVR), and MACE in all four categories were considered at 1, 6 and 12 months. Results We did not observe significant difference between phenotypes for MACE at 1 (p = 0.274), 6 (p = 0.387), and 12 months (p = 0.083). Death due to cardiac causes, MI, and bleeding events were not significant at 1, 6, and 12 months. There was no significant difference in TVR at 6 (p = 0.491), and 12 months (p = 0.423) except at 1 month (p = 0.012). Conclusion CYP2C19 genotype-based intervention can be implemented effectively and reliably to guide selection of P2Y12 inhibitor to optimize patient quality and safety when appropriate in post PCI patients.

Influenza A virus (IAV) and Streptococcus pyogenes (the group A Streptococcus; GAS) are important contributors to viral-bacterial superinfections, which result from incompletely defined mechanisms. We identified changes in gene expression following IAV infection of A549 cells. Changes included an increase in transcripts encoding proteins with fibronectin-type III (FnIII) domains, such as fibronectin (Fn), tenascin N (TNN), and tenascin C (TNC). We tested the idea that increased expression of TNC may affect the outcome of an IAV-GAS superinfection. To do so, we created a GAS strain that lacked the Fn-binding protein PrtF.2. We found that the wild-type GAS strain, but not the mutant, co-localized with TNC and bound to purified TNC. In addition, adherence of the wild-type strain to IAV-infected A549 cells was greater compared to the prtF.2 mutant. The wild-type strain was also more abundant in the lungs of mice 24 hours after superinfection compared to the mutant strain. Finally, all mice infected with IAV and the prtF.2 mutant strain survived superinfection compared to only 42% infected with IAV and the parental GAS strain, indicating that PrtF.2 contributes to virulence in a murine model of IAV-GAS superinfection.

Numerous studies have confirmed the importance of advance care planning. Despite the benefits of directed end-of-life discussions, a variety of barriers including discomfort with the topic, physician ideology, lack of time and reimbursement, delaying discussions, and lack of training impede physicians from facilitating these crucial conversations with their patients. This study aims to understand physicians' perceptions to additional barriers to advance care planning with patients and their families.Interviews with 19 practicing physicians (seven women and 12 men). Their perceptions were noted in interviews that were audiotaped, transcribed, and analyzed (n = 19).Physicians continue to face barriers to advance care planning as well as struggle with additional challenges such as difficulty with families, lack of patient education, inconsistencies and accessibility of advance directive documents, and lack of physician-physician communication or agreement in care. Further analysis reveals contradictions regarding physician comfort level and the role of primary care. These results reveal the complexity of providing medical care and the continued need for improvements in physician-patient communication about end-of-life care.Complex challenges in communication impede the delivery of successful end-of-life experiences for patients and their families. With improvements in the practices of advance care planning, many of these challenges can be removed - enabling individuals to remain in control as they near the end of their lives and preventing unnecessary pain and suffering on behalf of the patient and family.