Provider survey of the roles of clinical pharmacists in primary care in a Federally Qualified Health Center versus an Accountable Care Organization

Background: Healthcare providers at primary care Federally Qualified Healthcare Centers (FQHC) and an Accountable Care Organizations (ACO) collaborated with clinical pharmacists in providing patient care utilizing the comprehensive medication management (CMM) framework. The intention of CMM was to generate more time for providers to see patients, and to improve overall patient quality of life. Objectives: The purpose of this study was to survey the providers' views of clinical pharmacy services, and to compare and contrast the shared-visit model in rural FQHCs and an ACO collaborative practice agreement model in a mid-sized metropolitan area. Methods: Primary care providers completed a five-domain 22-item survey of provider patient care, provider pharmacy consults, provider ranking of pharmacy-services, disease treatment and provider views on the value of clinical pharmacists. Results: FQHC pharmacists were available one day per week (75%), while 69% of ACO pharmacists were available five days per week. FQHC providers requested 10 consults per week (44%). Both organizations had nearly identical provider rankings and impact on patient care for clinical pharmacy services and disease-focused pharmacy services. The provider survey of satisfaction with pharmacy consultations were highly positive and scored as strongly agree with FQHC and ACO, with the exception of three items with the FQHC. Overall providers at both organizations report highly effective medication-related improvements, disease outcomes and also recommend clinical pharmacists to other providers and primary care teams. Regression analysis revealed relevant clinical associations between survey statements not seen with individual survey items alone. Conclusion: Primary care providers report high satisfaction with, and benefits of, clinical pharmacy services. Drug information resource and disease-focused management were documented by providers as valuable pharmacy services. Providers promoted expanding the role of clinical pharmacists with providers, and integration into primary care teams

The impact of BRAF mutation status on clinical outcomes with anti- PD- 1 monotherapy versus combination ipilimumab/nivolumab in treatment- naïve advanced stage melanoma

Nearly half of all metastatic melanoma patients possess the BRAF V600 mutation. Several therapies are approved for advanced stage melanoma, but it is unclear if there is a differential outcome to various immunotherapy regimens based on BRAF mutation status. We retrospectively analyzed a cohort of metastatic or unresectable melanoma patients who were treated with combination ipilimumab/nivolumab (ipi/nivo) or anti- PD- 1 monotherapy, nivolumab, or pembrolizumab, as first- line treatment. 235 previously untreated patients were identified in our study. Our univariate analysis showed no statistical difference in progression- free survival (PFS) or overall survival (OS) with ipi/nivo versus anti- PD- 1 monotherapy in the BRAF V600 mutant cohort, but there was improved PFS [HR: 0.48, 95% CI, 0.28- 0.80] and OS [HR: 0.50, 95% CI, 0.26- 0.96] with ipi/nivo compared to anti- PD- 1 monotherapy in the BRAF WT group. After adjusting for known prognostic variables in our multivariable analysis, the BRAF WT cohort continued to show PFS and OS benefit with ipi/nivo compared to anti- PD- 1 monotherapy. Our single- institution analysis suggests ipi/nivo should be considered over anti- PD- 1 monotherapy as the initial immunotherapy regimen for metastatic melanoma patients regardless of BRAF mutation status, but possibly with greater benefit in BRAF WT.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/167487/1/pcmr12944_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/167487/2/pcmr12944.pd

Exploration of Benzothiazole Rhodacyanines as Allosteric Inhibitors of Protein–Protein Interactions with Heat Shock Protein 70 (Hsp70)

Cancer cells rely on the chaperone heat shock protein 70 (Hsp70) for survival and proliferation. Recently, benzothiazole rhodacyanines have been shown to bind an allosteric site on Hsp70, interrupting its binding to nucleotide-exchange factors (NEFs) and promoting cell death in breast cancer cell lines. However, proof-of-concept molecules, such as JG-98, have relatively modest potency (EC₅₀ ≈ 0.7–0.4 μM) and are rapidly metabolized in animals. Here, we explored this chemical series through structure- and property-based design of ∼300 analogs, showing that the most potent had >10-fold improved EC₅₀ values (∼0.05 to 0.03 μM) against two breast cancer cells. Biomarkers and whole genome CRISPRi screens confirmed members of the Hsp70 family as cellular targets. On the basis of these results, JG-231 was found to reduce tumor burden in an MDA-MB-231 xenograft model (4 mg/kg, ip). Together, these studies support the hypothesis that Hsp70 may be a promising target for anticancer therapeutics