Integrating Interprofessional Education and Cultural Competency Training to Address Health Disparities.

PROBLEM: Many U.S. medical schools have accreditation requirements for interprofessional education and training in cultural competency, yet few programs have developed programs to meet both of these requirements simultaneously. Furthermore, most training programs to address these requirements are broad in nature and do not focus on addressing health disparities. The lack of integration may reduce the students' ability to apply the knowledge learned. Innovative programs that combine these two learning objectives and focus on disenfranchised communities are needed to train the next generation of health professionals. INTERVENTION: A unique interprofessional education program was developed at the University of Arkansas for Medical Sciences Northwest. The program includes experiential learning, cultural exposure, and competence-building activities for interprofessional teams of medicine, nursing, and pharmacy students. The activities include (a) educational seminars, (b) clinical experiential learning in a student-led clinic, and (c) community-based service-learning through health assessments and survey research events. CONTEXT: The program focuses on interprofessional collaboration to address the health disparities experienced by the Marshallese community in northwest Arkansas. The Marshallese are Pacific Islanders who suffer from significant health disparities related to chronic and infectious diseases. OUTCOME: Comparison tests revealed statistically significant changes in participants' retrospectively reported pre/posttest scores for Subscales 1 and 2 of the Readiness for Interpersonal Learning Scale and for the Caffrey Cultural Competence in Healthcare Scale. However, no significant change was found for Subscale 3 of the Readiness for Interpersonal Learning Scale. Qualitative findings demonstrated a change in students' knowledge, attitudes, and behavior toward working with other professions and the underserved population. LESSONS LEARNED: The program had to be flexible enough to meet the educational requirements and class schedules of the different health professions' education programs. The target community spoke limited English, so providing interpretation services using bilingual Marshallese community health workers was integral to the program's success.

Pilot Implementation of Adapted-Family Diabetes Self-Management Education Into a Clinical Setting.

Objectives: Marshallese are a Pacific Islander community that experience a disproportionate rate of type 2 diabetes. The purpose of this study is to evaluate the preliminary effectiveness and feasibility of an Adapted-Family Diabetes Self-Management Education (DSME) intervention among Marshallese adults diagnosed with type 2 diabetes and their family members when delivered in a clinical setting. Methods: Marshallese patients (primary participants) with type 2 diabetes (n = 10) and their family members (n = 10) enrolled in a pilot study deigned to evaluate an Adapted-Family DSME curriculum conducted by community health workers and a certified diabetes educator in a clinical setting. Primary and family participants' health information and biometric data (HbA1c, blood pressure, cholesterol, and body mass index) were collected at preintervention and 12 weeks postintervention. Results: All 10 primary participants and 8 of the family members received all 10 hours of the education intervention. Nine of the 10 primary participants and 8 of the 10 family members completed the pre- and postintervention data collection events. Primary participants demonstrated a mean decrease in HbA1c of 0.7%, from pre- to postintervention, as well as improved blood pressure and cholesterol. Family members demonstrated minor improvements in HbA1c and blood pressure. Conclusions: Results suggest preliminary effectiveness and feasibility of the Adapted-Family DSME in a clinic setting and will inform implementation of a fully powered study.

Phosphatidylinositol 4-kinasebeta is critical for functional association of rab11 with the Golgi complex.

Phosphatidylinositol 4-kinasebeta (PI4Kbeta) plays an essential role in maintaining the structural integrity of the Golgi complex. In a search for PI4Kbeta-interacting proteins, we found that PI4Kbeta specifically interacts with the GTP-bound form of the small GTPase rab11. The PI4Kbeta-rab11 interaction is of functional significance because inhibition of rab11 binding to PI4Kbeta abolished the localization of rab11 to the Golgi complex and significantly inhibited transport of vesicular stomatitis virus G protein from the Golgi complex to the plasma membrane. We propose that a novel function of PI4Kbeta is to act as a docking protein for rab11 in the Golgi complex, which is important for biosynthetic membrane transport from the Golgi complex to the plasma membrane.

Leveraging community-based participatory research capacity to recruit Pacific Islanders into a genetics study.

Pacific Islanders face many health disparities, including higher rates of cardiovascular disease, cancer, obesity, and diabetes compared to other racial and ethnic groups. Specifically, the Marshallese population suffers disproportionately from type 2 diabetes, with rates 400% higher than the general US population. As part of an ongoing community-based participatory research (CBPR) partnership, 148 participants were recruited for a study examining genetic variants to better understand diabetes. Participants provided a saliva specimen in an Oragene® DNA self-collection kit. Each participant provided approximately 2 mL volume of saliva and was asked qualitative questions about their experience. The study yielded a recruitment rate of 95.5%. Among the 148 persons who participated, 143 (96.6%) agreed to be contacted for future studies; 142 (95.9%) agreed to have their samples used for future IRB-approved studies; and 144 (97.3%) gave permission for the researchers to link information from this study to other studies in which they had participated. Qualitative responses showed that the majority of participants were willing to participate because of their desire to contribute to the health of their community and to understand the genetic influence related to diabetes. This study demonstrates willingness to participate in genetic research among Marshallese living in Arkansas. Willingness was likely enhanced because the feasibility study was part of a larger CBPR effort. This study is important to community stakeholders who have voiced a desire to collaboratively conduct genetic research related to diabetes, perinatal outcomes, and cancer.

A phase I study of intraperitoneal nanoparticulate paclitaxel (Nanotax®) in patients with peritoneal malignancies.

PURPOSE: This multicenter, open-label, dose-escalating, phase I study evaluated the safety, tolerability, pharmacokinetics and preliminary tumor response of a nanoparticulate formulation of paclitaxel (Nanotax®) administered intraperitoneally for multiple treatment cycles in patients with solid tumors predominantly confined to the peritoneal cavity for whom no other curative systemic therapy treatment options were available. METHODS: Twenty-one patients with peritoneal malignancies received Nanotax® in a modified dose-escalation approach utilizing an accelerated titration method. All patients enrolled had previously received chemotherapeutics and undergone surgical procedures, including 33 % with optimal debulking. Six doses (50-275 mg/m(2)) of Cremophor-free Nanotax® were administered intraperitoneally for one to six cycles (every 28 days). RESULTS: Intraperitoneal (IP) administration of Nanotax® did not lead to increases in toxicity over that typically associated with intravenous (IV) paclitaxel. No patient reported ≥Grade 2 neutropenia and/or ≥Grade 3 neurologic toxicities. Grade 3 thrombocytopenia unlikely related to study medication occurred in one patient. The peritoneal concentration-time profile of paclitaxel rose during the 2 days after dosing to peritoneal fluid concentrations 450-2900 times greater than peak plasma drug concentrations and remained elevated through the entire dose cycle. Best response assessments were made in 16/21 patients: Four patients were assessed as stable or had no response and twelve patients had increasing disease. Five of 21 patients with advanced cancers survived longer than 400 days after initiation of Nanotax® IP treatment. CONCLUSIONS: Compared to IV paclitaxel administration, Cremophor-free IP administration of Nanotax® provides higher and prolonged peritoneal paclitaxel levels with minimal systemic exposure and reduced toxicity.

Oral vinorelbine for the treatment of metastatic non-small cell lung cancer in elderly patients: a phase II trial of efficacy and toxicity.

PURPOSE: Before now oral vinorelbine has not yet been tested in a cohort of elderly, advanced non-small cell lung cancer patients, even though the intravenous form of this drug provides a reasonable therapeutic option for this group. This trial was conducted to determine the tumor response rate and toxicity profile of oral vinorelbine in advanced non-small cell lung cancer patients > or = 65 years of age. PATIENT AND METHODS: Fifty-eight evaluable patients > or = 65 years of age with advanced non-small cell lung cancer were enrolled. Median age was 73 years (range: 65-87). The Eastern Cooperative Oncology Group (ECOG) performance score was 0, 1, or 2 in 29, 59, and 12% of patients, respectively. All patients had adequate organ function. Oral vinorelbine 60 mg/m2 per week was prescribed weekly as first-line therapy. RESULTS: Two patients manifested a confirmed tumor response, yielding a response rate of 3.4% (95% confidence interval (CI): 0.4, 11.9%). There were no complete responses. Median progression-free survival was 3.5 months (95% CI: 2.2, 5.4 months), and median overall survival was 7.5 months (95% CI: 5.0, 12 months). There were five deaths, one of which might have been treatment-related, and there were 10 grade 4 events. CONCLUSIONS: Oral vinorelbine, as prescribed in this trial, provides minimal activity in the treatment of advanced non-small cell lung cancer in patients > or = 65 years of age.

Cardiac angiosarcoma presenting with tamponade.

Primary cardiac angiosarcoma is extremely rare, but it is the most common primary malignant cardiac tumor. We herein present the case of a 51-year-old man who presented with symptoms of acute right heart failure, secondary to pericardial tamponade. Pericardiocentesis showed bloody fluid with negative pathology. Repeat 2-D echocardiography and a trans-esophageal echocardiogram showed a right atrial mass. The patient underwent surgery and adjuvant chemotherapy, but died seven months after the diagnosis. Despite being rare, cardiac angiosarcoma should be included in the differential diagnosis of bloody pericardial effusions, even with negative early investigations. The prognosis of the disease is usually poor. Treatment is mainly surgical resection if the cancer is localized, and can include neadjuvant and adjuvant chemotherapy, radiation treatment, and immunotherapy.

Sorafenib in platinum-treated patients with extensive stage small cell lung cancer: a Southwest Oncology Group (SWOG 0435) phase II trial.

INTRODUCTION: Sorafenib is a multikinase inhibitor affecting pathways involved in tumor progression and angiogenesis. We conducted a phase II trial of sorafenib in platinum-treated patients with extensive stage small cell lung cancer to determine the tumor response rate, toxicity, and overall survival. METHODS: Patients with histologically confirmed, measurable disease, Zubrod performance status 0 to 1, and no more than 1 prior platinum-based treatment were eligible. Patients were stratified by platinum-sensitivity status: sensitive (progression >90 days after platinum) or refractory (progression during or ≤90 days after platinum). Patients were treated with sorafenib 400 mg orally twice a day continuously on a 28-day cycle. RESULTS: Of 89 patients registered, 82 were evaluable for toxicity assessment, and 83 were evaluable for response. There were four partial responses seen among the 38 patients in the platinum-sensitive stratum, for an estimated response rate of 11% (95% confidence interval: 3-25%), and one partial response among the 45 patients in the platinum-refractory stratum, for an estimated response rate of 2% (95% confidence interval: 0-12%). The median overall survival estimates were 6.7 months (95% confidence interval: 6.1-9.1 months) for the platinum-sensitive stratum and 5.3 months (95% confidence interval: 3.3-7.5 months) in the platinum-refractory stratum. Nineteen patients discontinued treatment because of adverse events or side effects from therapy. CONCLUSIONS: Based on the lack of disease control seen in our trial, further investigation of single-agent sorafenib in the small cell lung cancer population is not recommended. Combination trials of sorafenib and chemotherapy are ongoing.

Nuclear localization of phosphatidylinositol 4-kinase beta.

Whereas most phosphatidylinositol 4-kinase (PtdIns 4-kinase) activity is localized in the cytoplasm, PtdIns 4-kinase activity has also been detected in membrane-depleted nuclei of rat liver and mouse NIH 3T3 cells. Here we have characterized the PtdIns 4-kinase that is present in nuclei from NIH 3T3 cells. Both type II and type III PtdIns 4-kinase activity were observed in the detergent-insoluble fraction of NIH 3T3 cells. Dissection of this fraction into cytoplasmic actin filaments and nuclear lamina-pore complexes revealed that the actin filament fraction contains solely type II PtdIns 4-kinase, whereas lamina-pore complexes contain type III PtdIns 4-kinase activity. Using specific antibodies, the nuclear PtdIns 4-kinase was identified as PtdIns 4-kinase beta. Inhibition of nuclear export by leptomycin B resulted in an accumulation of PtdIns 4-kinase beta in the nucleus. These data demonstrate that PtdIns 4-kinase beta is present in the nuclei of NIH 3T3 fibroblasts, suggesting a specific function for this kinase in nuclear processes.