Factors that impact risk management decisions among women with pathogenic variants in moderate penetrance genes associated with hereditary breast cancer.

There is limited information known about how women with pathogenic variants (PV) in moderate penetrance genes make decisions to manage their increased risk of breast cancer. This study analyzed factors that may impact decision-making surrounding management for increased breast cancer risk. Women with a PV in a moderate penetrance gene associated with increased risk for breast cancer were identified from an institutional database. Semi-structured, qualitative interviews were conducted to analyze decision-making factors. Themes were developed using deductive codes based on previous literature and inductive codes based on interviewee responses. The 16 participants (mean age = 55.9 years) included 12 women with a breast cancer diagnosis. Six women (37.5%) chose bilateral mastectomy (BM), and 10 women (62.5%) chose surveillance as management. Of the 12 women with a personal history of breast cancer, four chose to have BM (33.3%). Two women without a personal history of breast cancer chose to have BM (50.0%). Transcriptions revealed seven comprehensive themes, as well as themes unique to affected and unaffected women (Cohen's kappa = 0.80). Physician opinion was the only factor present in all interviews reported to influence risk management decision-making. Several themes were consistent with prior BRCA1/BRCA2 research (family history, risk perception, sibling influence, and physician opinions). Autonomy and insurance/finances were also important factors to participants. There were certain differences in decision-making factors between affected and unaffected women, such as partner influence. Results indicate an opportunity for providers to engage their patients in a decision-making process.

Factors Influencing Clinical Follow-Up for Individuals with a Personal History of Breast and/or Ovarian Cancer and Previous Uninformative BRCA1 and BRCA2 Testing.

Genetic testing for inherited cancer risk has recently improved through the advent of multi-gene panels and the addition of deletion and duplication analysis of the BRCA genes. The primary aim of this study was to determine which factors influence the intent of individuals with a personal history of breast and/or ovarian cancer and negative or uncertain BRCA1 and BRCA2 testing to return to a hereditary cancer program for additional genetic risk assessment, counseling, and testing. Surveys were sent to 1197 individuals and 257 were returned. Of those participants who were planning to return to clinic, most cited having family members who could benefit from the test result as the primary motivation to return. Many participants who were not planning to return to clinic cited the cost of testing as a barrier to return. Cost of testing and concerns about insurance coverage were the most commonly cited barriers for the group of participants who were undecided about returning to clinic. Results from this study may be used to guide re-contact efforts by clinicians to increase patient uptake to return to clinic for up-to-date genetic risk assessment, counseling, and testing.

Applying U.S. national guidelines for ototoxicity monitoring in adult patients: perspectives on patient populations, service gaps, barriers and solutions.

OBJECTIVES: To promote establishment of effective ototoxicity monitoring programs (OMPs), this report reviews the U.S. national audiology guidelines in relation to "real world" OMP application. Background is provided on the mechanisms, risks and clinical presentation of hearing loss associated with major classes of ototoxic medications. DESIGN: This is a non-systematic review using PubMed, national and international agency websites, personal communications between ototoxicity experts, and results of unpublished research. Examples are provided of OMPs in various healthcare settings within the U.S. civilian sector, Department of Defense (DoD), and Department of Veterans Affairs (VA). STUDY SAMPLE: The five OMPs compared in this report represent a convenience sample of the programs with which the authors are affiliated. Their opinions were elicited via two semi-structured teleconferences on barriers and facilitators of OMP, followed by a self-administered questionnaire on OMP characteristics and practices, with responses synthesized herein. Preliminary results are provided from an ongoing VA clinical trial at one of these OMP sites. Participants were 40 VA patients who received cisplatin chemotherapy in 2014-2017. The study arms contrast access to care for OMP delivered on the treatment unit versus usual care as provided in the audiology clinic. RESULTS: Protocols of the OMPs examined varied, reflecting their diverse settings. Service delivery concerns included baseline tests missed or completed after the initial treatment, and monitoring tests done infrequently or only after cessation of treatment. Perceived barriers involved logistics related to accessing and testing patients, such as a lack of processes to help patients enter programs, patients' time and scheduling constraints, and inconvenient audiology clinic locations. Use of abbreviated or screening methods facilitated monitoring. CONCLUSIONS: The most effective OMPs integrated audiological management into care pathways of the clinical specialties that prescribe ototoxic medications. More OMP guidance is needed to inform evaluation schedules, outcome reporting, and determination of actionable ototoxic changes. Guidance is also lacking on the use of hearing conservation approaches suitable for the mass testing needed to support large-scale OMP efforts. Guideline adherence might improve with formal endorsement from organizations governing the medical specialty stakeholders in OMP such as oncologists, pulmonologists, infectious disease specialists, ototolaryngologists and pharmacists.

Phenotypic properties of transmitted founder HIV-1.

Defining the virus-host interactions responsible for HIV-1 transmission, including the phenotypic requirements of viruses capable of establishing de novo infections, could be important for AIDS vaccine development. Previous analyses have failed to identify phenotypic properties other than chemokine receptor 5 (CCR5) and CD4+ T-cell tropism that are preferentially associated with viral transmission. However, most of these studies were limited to examining envelope (Env) function in the context of pseudoviruses. Here, we generated infectious molecular clones of transmitted founder (TF; n = 27) and chronic control (CC; n = 14) viruses of subtypes B (n = 18) and C (n = 23) and compared their phenotypic properties in assays specifically designed to probe the earliest stages of HIV-1 infection. We found that TF virions were 1.7-fold more infectious (P = 0.049) and contained 1.9-fold more Env per particle (P = 0.048) compared with CC viruses. TF viruses were also captured by monocyte-derived dendritic cells 1.7-fold more efficiently (P = 0.035) and more readily transferred to CD4+ T cells (P = 0.025). In primary CD4+ T cells, TF and CC viruses replicated with comparable kinetics; however, when propagated in the presence of IFN-α, TF viruses replicated to higher titers than CC viruses. This difference was significant for subtype B (P = 0.000013) but not subtype C (P = 0.53) viruses, possibly reflecting demographic differences of the respective patient cohorts. Together, these data indicate that TF viruses are enriched for higher Env content, enhanced cell-free infectivity, improved dendritic cell interaction, and relative IFN-α resistance. These viral properties, which likely act in concert, should be considered in the development and testing of AIDS vaccines.

Transmitted/founder and chronic subtype C HIV-1 use CD4 and CCR5 receptors with equal efficiency and are not inhibited by blocking the integrin α4ß7.

Sexual transmission of human immunodeficiency virus type 1 (HIV-1) most often results from productive infection by a single transmitted/founder (T/F) virus, indicating a stringent mucosal bottleneck. Understanding the viral traits that overcome this bottleneck could have important implications for HIV-1 vaccine design and other prevention strategies. Most T/F viruses use CCR5 to infect target cells and some encode envelope glycoproteins (Envs) that contain fewer potential N-linked glycosylation sites and shorter V1/V2 variable loops than Envs from chronic viruses. Moreover, it has been reported that the gp120 subunits of certain transmitted Envs bind to the gut-homing integrin α4ß7, possibly enhancing virus entry and cell-to-cell spread. Here we sought to determine whether subtype C T/F viruses, which are responsible for the majority of new HIV-1 infections worldwide, share biological properties that increase their transmission fitness, including preferential α4ß7 engagement. Using single genome amplification, we generated panels of both T/F (n = 20) and chronic (n = 20) Env constructs as well as full-length T/F (n = 6) and chronic (n = 4) infectious molecular clones (IMCs). We found that T/F and chronic control Envs were indistinguishable in the efficiency with which they used CD4 and CCR5. Both groups of Envs also exhibited the same CD4+ T cell subset tropism and showed similar sensitivity to neutralization by CD4 binding site (CD4bs) antibodies. Finally, saturating concentrations of anti-α4ß7 antibodies failed to inhibit infection and replication of T/F as well as chronic control viruses, although the growth of the tissue culture-adapted strain SF162 was modestly impaired. These results indicate that the population bottleneck associated with mucosal HIV-1 acquisition is not due to the selection of T/F viruses that use α4ß7, CD4 or CCR5 more efficiently.

Hospital and Health Plan Partnerships: The Affordable Care Act's Impact on Promoting Health and Wellness.

BACKGROUND: The Affordable Care Act (ACA) healthcare reforms, centered on achieving the Centers for Medicare & Medicaid Services (CMS) Triple Aim goals of improving patient care quality and satisfaction, improving population health, and reducing costs, have led to increasing partnerships between hospitals and insurance companies and the implementation of employee wellness programs. Hospitals and insurance companies have opted to partner to distribute the risk and resources and increase coordination of care. OBJECTIVE: To examine the ACA's impact on the health and wellness programs that have resulted from the joint ventures of hospitals and health plans based on the published literature. METHOD: We conducted a review of the literature to identify successful mergers and best practices of health and wellness programs. Articles published between January 2007 and January 2015 were compiled from various search engines, using the search terms "corporate," "health and wellness program," "health plan," "insurance plan," "hospital," "joint venture," and "vertical merger." Publications that described consolidations or wellness programs not tied to health insurance plans were excluded. Noteworthy characteristics of these programs were summarized and tabulated. RESULTS: A total of 44 eligible articles were included in the analysis. The findings showed that despite rising healthcare costs, joint ventures prevent hospitals from trading-off quality and services for cost reductions. Administrators believed that partnering would allow the companies to meet ACA standards for improving clinical outcomes at reduced costs. Before the implementation of the ACA, some employers had wellness programs, but these were not standardized and did not need to produce measurable results. The ACA encouraged improvement of employee wellness programs by providing funding for expanded health services and by mandating quality care. Successful workplace health and wellness programs have varying components, but all include monetary incentives and documented outcomes. CONCLUSION: The concurrent growth of hospital health plans (especially those emerging from vertical mergers and partnerships) and wellness programs in the United States provides a unique opportunity for employees and patient populations to promote wellness and achieve the Triple Aim goals as initiated by CMS.

Talking About Type 2 Diabetes: Family Communication From the Perspective of At-Risk Relatives.

PURPOSE: The purpose of this study was to describe type 2 diabetes (T2DM) communication and risk reduction recommendations from the perspective of family members at risk for T2DM based on family history. METHODS: Semistructured qualitative interviews were conducted with 33 individuals with a first-degree relative with T2DM. Participants were recruited from the community and a previous pharmacogenetics study. Deductive and inductive codes were applied to the transcripts. RESULTS: Conversations with family members with and without T2DM focused on symptoms and disease management of the family member with T2DM. With at-risk relatives, conversations also focused on prevention. Lack of perceived relevance to family members without T2DM was a barrier to communication. Recommendations to facilitate communication included education of an at-risk family member to increase awareness of risk, followed by sharing of learned information with others. CONCLUSION: Efforts are needed to increase awareness and improve communication about T2DM risk factors, familial risk, and risk reduction behaviors within families with a family history of T2DM. Family members with and without T2DM should be encouraged to communicate with their relatives about T2DM and the risk to family members. Identification of family members who can facilitate communication, education, and modeling of healthy behaviors may increase awareness and motivate at-risk individuals to engage in risk-reducing behaviors.