Engagement in Health Care From the Perspective of Older Adults.

Patient engagement is essential for improving health outcomes and lowering health care costs. The use of patient portals is becoming increasingly important for patient health care engagement. A convenience sample of 100 community-dwelling older adults completed a battery of surveys to explore the use of patient portals as an engagement tool. Criterion sampling was used to select a subset of 23 participants from the initial telephone survey to participate in one of four focus groups based on prior experience with a patient health portal (yes or no) and level of health literacy (low or high). Two core concepts and corresponding themes emerged: Patient Engagement Behaviors included the themes of managing health care, collaborating with providers, relying on family support, being proactive, advocating for health care, and seeking information. Patient-Provider Interactions included the themes of providers coordinate care, providers they can trust, two-way communication with providers, providers know them well, and providers give essential health information. Findings revealed a synergistic relationship among Patient Engagement Behaviors, Patient-Provider Interactions, and family support that can be strengthened in combination to promote the health care engagement capacity of older adults. [Research in Gerontological Nursing, 14(3), 138-149.].

The effects of extra high dose rate irradiation on glioma stem-like cells.

Radiation therapy is an integral part of treatment for patients with glioblastoma. New technological advances in linear accelerators have made extra-high dose rate irradiation possible. This shortens patient treatment time significantly compared to standard dose rate irradiation, but the biologic effects of extra high dose rate irradiation are poorly understood. Glioma stem-like cells (GSCs) are resistant to standard radiation and contribute to tumor progression. Here, we assess the therapeutic effect of extra high dose rate vs. standard dose rate irradiation on GSCs. GSCs were exposed to 2, 4 and 6 Gy X-irradiation at dose rates of 4.2 Gy/min or 21.2 Gy/min (400 monitoring units (MU)/min or 2100 MU/min). We analyzed cell survival with cell growth assays, tumorsphere formation assays and colony formation assays. Cell kill and self-renewal were dependent on the total dose of radiation delivered. However, there was no difference in survival of GSCs or DNA damage repair in GSCs irradiated at different dose rates. GSCs exhibited significant G1 and G2/M phase arrest and increased apoptosis with higher doses of radiation but there was no difference between the two dose rates at each given dose. In a GSC-derived preclinical model of glioblastoma, radiation extended animal survival, but there was no difference in survival in mice receiving different dose rates of radiation. We conclude that GSCs respond to larger fractions of radiation, but extra high dose rate irradiation has no significant biologic advantage in comparison with standard dose rate irradiation.

Patient Portals as a Tool for Health Care Engagement: A Mixed-Method Study of Older Adults With Varying Levels of Health Literacy and Prior Patient Portal Use.

BACKGROUND: Growing evidence that patient engagement improves health outcomes and reduces health care costs has fueled health providers' focus on patient portals as the primary access point for personal health information and patient-provider communication. Whereas much attention has been given to identifying characteristics of older adults who do and do not adopt patient portals and necessary adaptions to portal design, little is known about their attitudes and perceptions regarding patient portal use as a tool for engagement in their health care within the context of health literacy, experience navigating Web-based health information, and previous patient portal use. OBJECTIVE: The specific aims of this study were to explore attitudes toward portal adoption and its perceived usefulness as a tool for health care engagement among adults (65 years and older) who have varying levels of health literacy and degrees of prior patient portal use. METHODS: A phone survey of 100 community dwelling adults gathered sociodemographic, health, and technology related information. Older adults were purposefully selected for 4 follow-up focus groups based on survey responses to health literacy and previous patient portal use. A mixed-method approach was used to integrate phone survey data with thematic analysis of 4 focus groups. Due to variability in attitudes between focus group participants, an individual case analysis was performed and thematic patterns were used as the basis for subgroup formation. RESULTS: Differences in health literacy, comfort navigating health information on the Web, and previous portal experience explained some but not all differences related to the 7 themes that emerged in the focus groups analysis. Individual cases who shared attitudes were arranged into 5 subgroups from least to most able and willing to engage in health care via a patient portal. The subgroups' overall portal adoption attitudes were: (1) Don't want to feel pushed into anything, (2) Will only adopt if required, (3) Somebody needs to help me, (4) See general convenience of the portal for simple tasks and medical history, but prefer human contact for questions, and (5) Appreciates current features and excited about new possibilities . CONCLUSIONS: Most of the older adults are interested in using a patient portal regardless of health literacy level, previous patient portal adoption, or experience navigating health information on the Web. Research targeting informal caregivers of older adults who are unable or unwilling to engage with information technology in health care on their own is warranted. Health care organizations should consider tailored strategies to meet the needs of older adults (and their informal caregivers) and explore alternative workflows that integrate patient portal information into phone conversations and face-to-face contact with health care providers.

The Trp53 delta proline (Trp53ΔP) mouse exhibits increased genome instability and susceptibility to radiation-induced, but not spontaneous, tumor development.

The tumor suppressor TP53 can initiate a plethora of anti-proliferative effects to maintain genomic integrity under conditions of genotoxic stress. The N-terminal proline-rich domain (PRD) of TP53 is important in the regulation of TP53 activity and stability. A common polymorphism at codon 72 in this region has been associated with altered cancer risk in humans. The Trp53ΔP mouse, which carries a germline homozygous deletion of a region of the PRD, does not develop spontaneous tumors in a mixed 129/Sv and C57BL/6 genetic background, but is highly susceptible to a broad range of tumor types following total body exposure to 4 Gy gamma (γ) radiation. This contrasts with the tumor spectrum in Trp53 null (-/-) mice, which mainly develop thymic lymphomas and osteosarcomas. Analysis of genomic instability in tissues and cells from Trp53ΔP mice demonstrated elevated basal levels of aneuploidy, but this is not sufficient to drive spontaneous tumorigenesis, which requires an additional DNA damage stimulus. Levels of genomic instability did not increase significantly in Trp53ΔP mice following irradiation exposure, suggesting that other radiation effects including tissue inflammation, altered metabolism or autophagy, may play an important role. The Trp53ΔP mouse is a novel model to dissect the mechanisms of tumor development induced by radiation exposure. © 2015 Wiley Periodicals, Inc.

Hyperthermia Sensitizes Glioma Stem-like Cells to Radiation by Inhibiting AKT Signaling.

Glioma stem-like cells (GSC) are a subpopulation of cells in tumors that are believed to mediate self-renewal and relapse in glioblastoma (GBM), the most deadly form of primary brain cancer. In radiation oncology, hyperthermia is known to radiosensitize cells, and it is reemerging as a treatment option for patients with GBM. In this study, we investigated the mechanisms of hyperthermic radiosensitization in GSCs by a phospho-kinase array that revealed the survival kinase AKT as a critical sensitization determinant. GSCs treated with radiation alone exhibited increased AKT activation, but the addition of hyperthermia before radiotherapy reduced AKT activation and impaired GSC proliferation. Introduction of constitutively active AKT in GSCs compromised hyperthermic radiosensitization. Pharmacologic inhibition of PI3K further enhanced the radiosensitizing effects of hyperthermia. In a preclinical orthotopic transplant model of human GBM, thermoradiotherapy reduced pS6 levels, delayed tumor growth, and extended animal survival. Together, our results offer a preclinical proof-of-concept for further evaluation of combined hyperthermia and radiation for GBM treatment.

Sema3C promotes the survival and tumorigenicity of glioma stem cells through Rac1 activation.

Different cancer cell compartments often communicate through soluble factors to facilitate tumor growth. Glioma stem cells (GSCs) are a subset of tumor cells that resist standard therapy to contribute to disease progression. How GSCs employ a distinct secretory program to communicate with and nurture each other over the nonstem tumor cell (NSTC) population is not well defined. Here, we show that GSCs preferentially secrete Sema3C and coordinately express PlexinA2/D1 receptors to activate Rac1/nuclear factor (NF)-κB signaling in an autocrine/paracrine loop to promote their own survival. Importantly, Sema3C is not expressed in neural progenitor cells (NPCs) or NSTCs. Disruption of Sema3C induced apoptosis of GSCs, but not NPCs or NSTCs, and suppressed tumor growth in orthotopic models of glioblastoma. Introduction of activated Rac1 rescued the Sema3C knockdown phenotype in vivo. Our study supports the targeting of Sema3C to break this GSC-specific autocrine/paracrine loop in order to improve glioblastoma treatment, potentially with a high therapeutic index.