Publications

The efficacy of allogeneic hematopoietic stem cell transplantation for hematologic malignancies is limited by the difficulty in suppressing graft-versus-host disease (GVHD) without compromising graft-versus-tumor (GVT) effects. We previously showed that RAS/MEK/ERK signaling depends on memory differentiation in human T cells, which confers susceptibility to selective inhibition of naive T cells. Actually, antineoplastic MEK inhibitors selectively suppress alloreactive T cells, sparing virus-specific T cells in vitro. Here, we show that trametinib, a MEK inhibitor clinically approved for melanoma, suppresses GVHD safely without affecting GVT effects in vivo. Trametinib prolonged survival of GVHD mice and attenuated GVHD symptoms and pathology in the gut and skin. It inhibited ERK1/2 phosphorylation and expansion of donor T cells, sparing Tregs and B cells. Although high-dose trametinib inhibited myeloid cell engraftment, low-dose trametinib suppressed GVHD without severe adverse events. Notably, trametinib facilitated the survival of mice transplanted with allogeneic T cells and P815 tumor cells with no residual P815 cells observed in the livers and spleens, whereas tacrolimus resulted in P815 expansion. These results confirm that trametinib selectively suppresses GVHD-inducing T cells while sparing antitumor T cells in vivo, which makes it a promising candidate for translational studies aimed at preventing or treating GVHD.

Homeostasis of the gastrointestinal (GI) tract is controlled by complex interactions between epithelial and immune cells and the resident microbiota. Here, we studied the role of Wnt signaling in GI homeostasis using knockout () mice, which display an increase in whole gut transit time. This phenotype is associated with a reduction and mislocalization of Paneth cells and an increase in CD8 T cells in the lamina propria. Bone marrow chimera experiments demonstrated that GI dysfunction requires abnormalities in both epithelial and immune cells. mice exhibit a significantly distinct GI microbiota, and manipulation of the gut microbiota in mutant mice rescued the GI transit abnormality without correcting the Paneth and CD8 T cell abnormalities. Moreover, manipulation of the gut microbiota in wild-type mice induced a GI transit abnormality akin to that seen in mice. Together, these data indicate that microbiota manipulation can overcome host dysfunction to correct GI transit abnormalities. Our findings illustrate a mechanism by which the epithelium and immune system coregulate gut microbiota composition to promote normal GI function.

AIM

This study examined the career anchor characteristics that are possessed by Japanese occupational health nurses.

METHOD

Sixteen occupational health nurses participated in the semistructured interview. Data analyses were conducted using descriptive qualitative methods.

RESULTS

The data showed the following five categories: practices concerning relationships and positions; development of occupational health practices; management skills for effective work; practices that are approved inside and outside the organization; and work and private life considerations.

CONCLUSIONS

This study described the career anchors among occupational health nurses in Japan. The participants emphasized the following: the importance of maintaining good cooperative relationships with workers and supervisors; balancing professional and organized labor; and practicing effective occupational health services. Moreover, the occupational health nurses emphasized receiving approval from inside and outside of the organization. These results were consistent with the actual practices of occupational health nursing.

Early after HIV infection there is substantial depletion of CD4 T cells in the gastrointestinal (GI) tract lamina propria (LP), with associated epithelial barrier damage, leading to microbial translocation and systemic inflammation and immune activation. In this study, we analyzed these early events in the GI tract in a cohort of Thai acute HIV-infected patients and determined the effect of early combination antiretroviral treatment (cART). HIV-uninfected and chronically and acutely HIV-infected patients at different Fiebig stages (I-V) underwent colonic biopsies and then received cART. Immunohistochemistry and quantitative image analysis were performed on cross-sectional and longitudinal colon biopsy specimens (day 0 to week 96) to measure GI tract damage (infiltration of polymorphonuclear cells), inflammation (M×1, TNF-α), immune activation (Ki-67), and the CD4 T cell population in the LP. The magnitude of GI tract damage, immune activation, and inflammation was significantly increased, with significantly depleted CD4 T cells in the LP in all acutely infected groups prior to cART compared with HIV-uninfected control participants. While most patients treated during acute infection resolved GI tract inflammation and immune activation back to baseline levels after 24 weeks of cART, most acutely infected participants did not restore their CD4 T cells after 96 weeks of cART.

OBJECTIVES

To inform the development of a data-driven measure of quality care for individuals with multiple chronic conditions (MCCs) derived from an electronic health record (EHR).

DESIGN

Qualitative study using focus groups, interactive webinars, and a modified Delphi process.

SETTING

Research department within an integrated delivery system.

PARTICIPANTS

The webinars and Delphi process included 17 experts in clinical geriatrics and primary care, health policy, quality assessment, health technology, and health system operations. The focus group included 10 individuals aged 70-87 with three to six chronic conditions selected from a random sample of individuals aged 65 and older with three or more chronic medical conditions.

MEASUREMENTS

Through webinars and the focus group, input was solicited on constructs representing high-quality care for individuals with MCCs. A working list was created of potential measures representing these constructs. Using a modified Delphi process, experts rated the importance of each possible measure and the feasibility of implementing each measure using EHR data.

RESULTS

High-priority constructs reflected processes rather than outcomes of care. High-priority constructs that were potentially feasible to measure included assessing physical function, depression screening, medication reconciliation, annual influenza vaccination, outreach after hospital admission, and documented advance directives. High-priority constructs that were less feasible to measure included goal setting and shared decision-making, identifying drug-drug interactions, assessing social support, timely communication with patients, and other aspects of good customer service. Lower-priority domains included pain assessment, continuity of care, and overuse of screening or laboratory testing.

CONCLUSION

High-quality MCC care should be measured using meaningful process measures rather than outcomes. Although some care processes are currently extractable from electronic data, capturing others will require adapting and applying technology to encourage holistic, person-centered care.

BACKGROUND

To the authors' knowledge, few studies to date have evaluated the effects of survivorship care planning on the care transition process from specialty cancer care to self-management and primary care, patient experience, or health outcomes. The Patient-owned Survivorship Transition Care for Activated, Empowered survivors (POSTCARE) is a single coaching encounter based on the Chronic Care Model that uses motivational interviewing techniques to engage survivors of breast cancer. The current study examined the effects of the POSTCARE intervention on patient outcomes and care coordination.

METHODS

A total of 79 survivors of American Joint Commision on Cancer TNM System stage 0 to IIIB breast cancer were randomized to POSTCARE (40 patients) or usual care (39 patients). Patient outcomes were assessed using the 36-Item Short Form Health Survey (SF-36), Social/Role Activities Limitations, Self-Efficacy for Managing Chronic Disease 6-Item Scale, the Patient Activation Measure-Short Form, and Patient Health Questionnaire depression scale at baseline and at 3-month follow-up. Care coordination was assessed using confirmed primary care physician visits and reported discussion of the survivorship care plan at the 3-month follow-up. Logistic and linear regression analyses were conducted to examine the effect of POSTCARE on selected outcomes.

RESULTS

Participants in the intervention group versus those receiving usual care demonstrated significantly higher self-reported health (F-statistic (3,71), 3.63; P =.017) and lower social role limitations (F (3,70), 3.82; P =.014) and a trend toward greater self-efficacy (F (3,69), 2.51; P = .07). Three quality-of-life domains reached clinically meaningful improvement at the 3-month follow-up, including physical role (P =.0009), bodily pain (P =.03), and emotional role (P =.04).

CONCLUSIONS

The POSTCARE intervention appeared to have a positive impact on patient outcomes and demonstrated promise as a strategy with which to improve survivors' experience, care coordination, and health outcomes. Cancer 2016;122:3232-42. © 2016 American Cancer Society.

OBJECTIVES

To assess patient and caregiver perceptions of what constitutes quality care in home-based primary care (HBPC).

DESIGN

Cross-sectional qualitative design; semistructured interview study.

SETTING

Academic home-based primary care program.

PARTICIPANTS

Homebound patients (n = 13) and 10 caregivers (n = 10) receiving HBPC.

MEASUREMENTS

Semistructured interviews explored experiences with a HBPC program and perceptions of quality care. Interviews were audio-recorded and transcribed. Qualitative content analysis was performed to identify major themes.

RESULTS

Five major themes emerged related to participant perceptions of quality care: access, affordability, competency, care coordination, goal attainment. Participants felt that reliable, consistent access provided "peace of mind" and reduced hospital and emergency department use. Insurance coverage of program costs and coordinated care provided by an interdisciplinary team were positively regarded. Interpersonal skills and technical abilities of providers influenced patient perception of provider competency. Assessing and helping patients attain care goals contributed to a perception of quality care.

CONCLUSION

Patients and caregivers associate high-quality HBPC with around-the-clock access to affordable interdisciplinary providers with strong interpersonal skills and technical competency. These results expand on prior research and are concordant with HBPC goals of around-the-clock access to multidisciplinary teams with the goals of reduced emergency department and hospital use. HBPC programs should be structured to optimize access, affordability, coordinated care, and goal ascertainment and alignment. Quality indicators should be created and validated with these patient and caregiver views of care quality in mind.