Narrowing Cardiovascular Disease Health Disparities by Advancing the Role of Pharmacists Through a Multisector Consortium.

Demand for scaling and sustaining clinical services to improve health outcomes while minimizing costs is rising, particularly for patients dealing with major cardiovascular disease and stroke risk factors such as hypertension. Consequently, there is growing national and local interest in engaging pharmacists as part of the solution through the implementation of comprehensive medication management. To capitalize on this momentum, a team from the University of Southern California led the establishment of the California Right Meds Collaborative (CRMC) in 2019. CRMC aims to reduce the burden of uncontrolled chronic disease by advancing the role of pharmacists as team members in the health care system. This case study describes CRMC's structure and approach to developing value-based payment models and advancing the competency of pharmacists through training, continuous quality improvement, and technical assistance. In addition, this case study provides an overview of a CRMC pilot project wherein a local health plan tested a value-based payment model to deliver comprehensive medication management. The pilot underwent many iterative changes throughout its duration but ultimately was considered a success and adopted as part of standard practice. Lessons learned from this effort can help others leverage the availability of pharmacists to assist vulnerable populations in their communities.

Delivery of Comprehensive Medication Management and Other Clinical Services via Telehealth by Pharmacy Type.

BACKGROUND: The recent coronavirus pandemic accelerated the need to deliver pharmacy-related services remotely. OBJECTIVE: To describe experiences with providing comprehensive medication management (CMM) and other clinical services via telehealth by pharmacy type, before and during the COVID-19 pandemic. METHODS: An online survey of pharmacists, representing 27 pharmacies, was conducted to capture telehealth usage in three pharmacy types: independently owned, integrated into a clinical setting, and retail chain. A sub-analysis was performed to assess if providing CMM services via telehealth helped, resulted in no change, or worsened the care of different patient groups (e.g., those with diabetes, were low-income, aged 65+ years). RESULTS: During the pandemic, telehealth usage among independently owned pharmacies and those integrated into a clinical setting increased, but no change occurred among retail chain pharmacies. This usage increase in the first two pharmacy types occurred despite limited investments in connectivity-related resources to support telehealth services. Pharmacists from both independently owned pharmacies (63%) and those integrated into a clinical setting (89%) reported CMM via telehealth reached patients they would not otherwise have been able to reach during the pandemic. Most pharmacists/pharmacies found telehealth to be a feasible and acceptable method of delivering CMM. CONCLUSION: Pharmacists and pharmacies are now experienced with and have interest in continuing CMM via telehealth, even as the pandemic recedes. However, investments in telecommunications resources, training support, technical assistance, and continued telehealth reimbursement from health plans are needed to sustain this service delivery model.

Influencing the Tumor Microenvironment: A Phase II Study of Copper Depletion Using Tetrathiomolybdate in Patients with Breast Cancer at High Risk for Recurrence and in Preclinical Models of Lung Metastases.

PURPOSE: Bone marrow-derived progenitor cells, including VEGFR2+ endothelial progenitor cells (EPCs) and copper-dependent pathways, model the tumor microenvironment. We hypothesized that copper depletion using tetrathiomolybdate would reduce EPCs in high risk for patients with breast cancer who have relapsed. We investigated the effect of tetrathiomolybdate on the tumor microenvironment in preclinical models. EXPERIMENTAL DESIGN: Patients with stage II triple-negative breast cancer (TNBC), stage III and stage IV without any evidence of disease (NED), received oral tetrathiomolybdate to maintain ceruloplasmin (Cp) between 8 and 17 mg/dL for 2 years or until relapse. Endpoints were effect on EPCs and other biomarkers, safety, event-free (EFS), and overall survival (OS). For laboratory studies, MDA-LM2-luciferase cells were implanted into CB17-SCID mice and treated with tetrathiomolybdate or water. Tumor progression was quantified by bioluminescence imaging (BLI), copper depletion status by Cp oxidase levels, lysyl oxidase (LOX) activity by ELISA, and collagen deposition. RESULTS: Seventy-five patients enrolled; 51 patients completed 2 years (1,396 cycles). Most common grade 3/4 toxicity was neutropenia (3.7%). Lower Cp levels correlated with reduced EPCs (P = 0.002) and LOXL-2 (P < 0.001). Two-year EFS for patients with stage II-III and stage IV NED was 91% and 67%, respectively. For patients with TNBC, EFS was 90% (adjuvant patients) and 69% (stage IV NED patients) at a median follow-up of 6.3 years, respectively. In preclinical models, tetrathiomolybdate decreased metastases to lungs (P = 0.04), LOX activity (P = 0.03), and collagen crosslinking (P = 0.012). CONCLUSIONS: Tetrathiomolybdate is safe, well tolerated, and affects copper-dependent components of the tumor microenvironment. Biomarker-driven clinical trials in high risk for patients with recurrent breast cancer are warranted. Clin Cancer Res; 23(3); 666-76. ©2016 AACR.

Pulmonary artery banding alters the expression of Ca2+ transport proteins in the right atrium in rabbits.

Following pulmonary artery banding (PAB), the contractile function of right ventricle diminishes over time. Subsequently, the right atrium (RA) has to contract against a higher afterload, but it is unknown to what extent ventricular dysfunction has an effect on the atrial contractility. We hypothesized that right ventricular pressure overload may have an affect on atrial contractility and Ca(2+) transport protein expression. Therefore, we induced pressure overload of the right ventricle by PAB for 10 wk in rabbits and examined the changes in the expression of Ca(2+) transport proteins in the atrium. We demonstrate that PAB significantly decreased the expression of sarco(endo)plasmic reticulum Ca(2+)-ATPase (Serca) 2a while expression of Na(+)/Ca(2+) exchanger-1 was significantly upregulated in the RA but not in the left atria of rabbit hearts, indicating that pressure is the major trigger. A decrease in Serca2a expression was concomitant with a significant decrease in sarcolipin (SLN), possibly indicating a compensatory role of SLN. The decreased expression of SLN was unable to completely restore sarcoplasmic reticulum Ca(2+) uptake function of Serca2a. Functional contractile assessments in isolated trabeculae showed no difference between PAB- and sham-operated rabbits at 1 Hz but displayed an enhanced force development at higher frequencies and in the presence of isoproterenol, while twitch timing was unaffected. Our results indicate that right ventricular mechanical overload due to PAB affects the expression of the Ca(2+)-handling proteins in the RA in rabbits.

Identification of a pneumococcal glycosidase that modifies O-linked glycans.

Colonization of the airway by Streptococcus pneumoniae is typically asymptomatic; however, progression of bacteria beyond the oronasopharynx can cause diseases including otitis media and pneumonia. The mechanisms by which S. pneumoniae establishes and maintains colonization remain poorly understood. Both N-linked and O-linked glycans are abundant in the airway. Our previous research demonstrated that S. pneumoniae can sequentially deglycosylate N-linked glycans and suggested that this modification of sugar structures may aid in colonization. There is published evidence that S. pneumoniae expresses a secreted O-glycosidase that cleaves galactose beta1-3 N-acetylgalactosamine (Galbeta1-3GalNAc) from core-1 O-linked glycans; however, the biological function of this enzyme has not previously been determined. We established that the activity is not secreted but is instead surface associated in a sortase-dependent manner. Genome analysis revealed an open reading frame predicted to encode a sortase-dependent surface protein with sequence similarity to the O-glycosidase of Bifidobacterium longum. Deletion of this pneumococcal open reading frame confirmed that this gene encodes an O-glycosidase. Experiments using a model glycoconjugate demonstrated that this O-glycosidase, together with the neuraminidase NanA, is required for S. pneumoniae to cleave sialylated core-1 O-linked glycans. The ability of the O-glycosidase mutant to cleave this glycan structure was restored by both genetic complementation and the addition of O-glycosidase. The mutant showed a reduction in adherence to human airway epithelial cells and a significantly decreased ability to colonize the upper respiratory tract, suggesting that cleavage of core-1 O-linked glycans enhances the ability of S. pneumoniae to colonize the human airway.