Implementation and Effect of a Pharmacist-to-Pharmacist Transitions of Care Initiative on Ambulatory Care Sensitive Conditions.

BACKGROUND: One of the most vulnerable times in a patient's encounter with a health care system is during transitions of care (TOC), defined by the Joint Commission as the movement of a patient from one health care provider or setting to another. The use of a clinical pharmacist as a member of the care transitions team has received focused attention and shown improved benefit. OBJECTIVE: To determine the effect of a large-scale pharmacist-to-pharmacist TOC model where inpatient clinical pharmacists identify patients during a hospital stay, provide evidence-based care and education, and then coordinate follow-up with an outpatient clinical pharmacist who provided comprehensive medication management (CMM) under a scope of practice. METHODS: This was a multisite, single health care system, quasi-experimental, matched interrupted time series design study conducted at an integrated Veterans Affairs (VA) health care system. Patients admitted with a primary or secondary diagnosis of diabetes, hypertension, chronic obstructive pulmonary disease (COPD) and heart failure (HF) were included for enrollment. Clinical pharmacists rounding on inpatient medical teams provided evidence-based recommendations to optimize medications while coordinating follow-up by an outpatient clinical pharmacy specialist within 10 days of discharge for CMM. The primary endpoint of this study was to determine the effect on the composite all-cause 30-day acute care utilization rate (emergency department [ED] visit or hospital readmission) for patients discharged with a primary or secondary diagnosis of diabetes, hypertension, COPD, and HF compared with a comparator group of patients with similar discharge diagnosis before implementation of the TOC program. RESULTS: 484 patients (242 in each group, with 366 heart failure, 66 COPD, 10 hypertension, and 42 diabetes) were included for analysis. For the primary outcome of composite 30-day, all-cause acute care utilization rates, no statistically significant difference was identified, with 26.9% of patients in the intervention group and 28.9% in the historical group readmitted or seen in the ED within 30 days of discharge (P = 0.6852). Outcomes for the HF index acute care utilization rate (i.e., admission for the same disease state discharged with), including 30-day index readmissions (P = 0.0014), 30-day index ED visits (P = 0.0047), and 90-day index readmissions for HF (P < 0.0001) were significantly reduced. CONCLUSIONS: Our study is one of the first to identify at-risk patients using rounding clinical pharmacists in the acute care arena and coordination of care systematically with a clinical pharmacy specialist practicing under a scope of practice targeted for CMM. Although the overall primary endpoint was not met, a reduction in acute care utilization rates for HF at 30 and 90 days can be achieved. DISCLOSURES: No outside funding supported this research. The authors report no conflicts of interest.

Enhanced cytotoxicity in triple-negative and estrogen receptor­positive breast adenocarcinoma cells due to inhibition of the transient receptor potential melastatin-2 channel.

We previously demonstrated a unique protective role for the transient receptor potential, melastatin-2 (TRPM2) cation channel in breast cancer cells. In the present study, we investigated the chemotherapeutic effects elicited by inhibiting this protective role in metastatic breast adenocarcinoma cells. TRPM2 inhibition led to dose-dependent increases in MDA-MB-231 breast adenocarcinoma cell death after treatment with doxorubicin or the DNA-methylating agent, N-methyl-N'-nitro-N-nitrosoguanidine. Similar results were observed after RNAi silencing of TRPM2 in these cells after doxorubicin treatment. However, TRPM2 RNAi silencing also led to increased MCF-7 breast adenocarcinoma cell death after tamoxifen treatment, yet not in non-cancerous human mammary epithelial cells. These results thus revealed that TRPM2 inhibition selectively increased cytotoxicity in a triple-negative and an estrogen receptor-positive breast cancer cell line, with minimal deleterious effects in non-cancerous breast cells. Analysis of DNA damage revealed enhanced DNA damage levels in MCF-7 cells treated with doxorubicin due to TRPM2 inhibition. Analysis of cell death demonstrated that inhibition of apoptosis, caspase-independent cell death or autophagy failed to significantly reduce cell death induced by TRPM2 inhibition and chemotherapy. These results indicate that TRPM2 inhibition activates alternative pathways of cell death in breast cancer cells. Taken together, our results provide significant evidence that TRPM2 inhibition is a potential strategy to induce triple-negative and estrogen receptor-positive breast adenocarcinoma cell death via alternative cell death pathways. This is expected to provide a basis for inhibiting TRPM2 for the improved treatment of breast cancer, which potentially includes treating breast tumors that are resistant to chemotherapy due to their evasion of apoptosis.