Development of myotendinous-like junctions that anchor cardiac valves requires fibromodulin and lumican.

BACKGROUND: There are many patients that exhibit connective tissue related cardiac malformations but do not have mutations in collagen genes. The Small Leucine Rich Proteoglycans (SLRP) fibromodulin (FMOD) and lumican (LUM) bind collagen and regulate fibril assembly in other biological contexts. RESULTS: FMOD deficient mice and double deficient FMOD; LUM mice exhibited anomalies in regions where cardiac valve tissue interdigitates with adjacent muscle for support. Ectopic connective and/or myocardial tissue(s) was associated with the more severe cardiac valve anomalies in FMOD; LUM deficient mice. At postnatal day 0 (P0) there was an increase in the mesenchymal cell number in the regions where valve cusps anchor in FMOD; LUM deficient mice compared to WT. The cardiac valve anomalies correlated with the highest levels of FMOD expression in the heart and also where myotendinous junctions (MTJ) components biglycan, collagen type I alpha 1, and collagen type VI, are also localized. CONCLUSIONS: The postnatal assembly of the collagen-rich ECM in regions where cardiac valves anchor, that we have designated 'myotendinous-like junctions' (MTLJ) requires the SLRPs FMOD and LUM. Moreover, FMOD and LUM may facilitate mesenchymal cell differentiation in late stages of cardiac valve development. Developmental Dynamics 245:1029-1042, 2016. © 2016 Wiley Periodicals, Inc.

Lumican deficiency results in cardiomyocyte hypertrophy with altered collagen assembly.

The ability of the heart to adapt to increased stress is dependent on the modification of its extracellular matrix (ECM) architecture that is established during postnatal development as cardiomyocytes differentiate, a process that is poorly understood. We hypothesized that the small leucine-rich proteoglycan (SLRP) lumican (LUM), which binds collagen and facilitates collagen assembly in other tissues, may play a critical role in establishing the postnatal murine myocardial ECM. Although previous studies suggest that LUM deficient mice (lum(-/-)) exhibit skin anomalies consistent with Ehlers-Danlos syndrome, lum(-/-) hearts have not been evaluated. These studies show that LUM was immunolocalized to non-cardiomyocytes of the cardiac ventricles and its expression increased throughout development. Lumican deficiency resulted in significant (50%) perinatal death and further examination of the lum(-/-) neonatal hearts revealed an increase in myocardial tissue without a significant increase in cell proliferation. However cardiomyocytes from surviving postnatal day 0 (P0), 1 month (1 mo) and adult (4 mo) lum(-/-) hearts were significantly larger than their wild type (WT) littermates. Immunohistochemistry revealed that the increased cardiomyocyte size in the lum(-/-) hearts correlated with alteration of the cardiomyocyte pericellular ECM components collagenα1(I) and the class I SLRP decorin (DCN). Western blot analysis demonstrated that the ratio of glycosaminoglycan (GAG) decorated DCN to core DCN was reduced in P0 and 1 mo lum(-/-) hearts. There was also a reduction in the ß and γ forms of collagenα1(I) in lum(-/-) hearts. While the total insoluble collagen content was significantly reduced, the fibril size was increased in lum(-/-) hearts, indicating that LUM may play a role in collagen fiber stability and lateral fibril assembly. These results suggest that LUM controls cardiomyocyte growth by regulating the pericellular ECM and also indicates that LUM may coordinate multiple factors of collagen assembly in the murine heart. Further investigation into the role of LUM may yield novel therapeutic targets and/or biomarkers for patients with cardiovascular disease.

Participatory research to improve medication reconciliation for older adults in the community.

INTRODUCTION: Medication reconciliation, a technique that assists in aligning a care team's understanding of an individual's true medication regimen, is vital to optimize medication use and prevent medication errors. Historically, most medication reconciliation research has focused on institutional settings and transitional care, with comparatively little attention given to medication reconciliation in community settings. To optimize medication reconciliation for community-dwelling older adults, healthcare professionals and older adults must be engaged in co-designing processes that create sustainable approaches. METHODS: Academic researchers, older adults, and community- and health system-based healthcare professionals engaged in a participatory process to better understand medication reconciliation barriers and co-design solutions. The initiative consisted of two participatory research approaches: (1) Sparks Innovation Studios, which synthesized professional expertise and opinions, and (2) a Community Consultation Studio with older adults. Input from both groups informed a list of possible solutions and these were ranked based on evaluative criteria of feasibility, person-centeredness, equity, and sustainability. RESULTS: Sparks Innovation Studios identified a lack of ownership, fragmented healthcare systems, and time constraints as the leading barriers to medication reconciliation. The Community Consultation Studio revealed that older adults often feel dismissed in medical encounters and perceive poor communication with and among providers. The Community Consultation Studio and Sparks Innovation Studios resulted in four highly-ranked solutions to improve medication reconciliation: (1) support for older adults to improve health literacy and ownership; (2) ensuring medication indications are included on prescription labels; (3) trainings and incentives for front-line staff in clinic settings to become champions for medication reconciliation; and (4) electronic health record improvements that simplify active medication lists. CONCLUSION: Engaging community representatives with academic partners in the research process enhanced understanding of community priorities and provided a practical roadmap for innovations that have the potential to improve the well-being of community-dwelling older adults.

A state affiliate's utilization of ASHP's Practice Advancement Initiative 2030 to identify current state of practice and a process to prioritize goal achievement.

PURPOSE: The American Society of Health-System Pharmacists (ASHP) has been a long-standing supporter of advancing pharmacy practice, specifically in the area of pharmacy practice models. In 2019, ASHP began the planning to launch PAI (Practice Advancement Initiative) 2030. PAI 2030 describes and details a bold vision for patient care, medication use, and pharmacy practice over the next decade. This work represents an ambitious goal to continue to advance the profession of pharmacy for the betterment of our patients. While much has been accomplished with the PAI, there is little literature on PAI 2030 (the authors are unaware of any published examples). SUMMARY: The purpose of the article is to explain a novel state affiliate's prioritization of ASHP's PAI 2030 recommendations. In the spring of 2020, the North Carolina Association of Pharmacists (NCAP), the North Carolina state affiliate of ASHP, began discussions around PAI 2030. In the fall of 2020, prior to the NCAP Annual Convention, health system pharmacy leaders within NCAP developed a questionnaire to serve as a PAI 2030 self-assessment. This approach allowed a state affiliate to implement an innovative program to act on the recommendations from PAI 2030. After the prioritization, health system pharmacy leaders engaged in discussion to comment on what recommendations have been identified. The goal of this discussion was to provide NCAP a direction to pursue focused efforts to support recommendations of PAI 2030. Ultimately, NCAP seeks that this statewide approach would help advance pharmacy practice, and improve pharmacy practice across the state of North Carolina in collaboration with NCAP. CONCLUSION: This discussion illustrates how a state affiliate has pursued implementing PAI 2030. This approach provides a strategy for state affiliates in addressing the recommendations within PAI 2030. A novel statewide approach can help marshal resources to advance practice when health systems partner with a state affiliate.

Access to clinical pharmacy services in a pharmacist-physician covisit model.

BACKGROUND: A pharmacist-physician covisit model in which patients see both a pharmacist and physician on the same day was established in a primary care practice. Previously, patients were seen in a referrals-based model in which providers referred patients for clinical pharmacy services on a different day. OBJECTIVE: To assess access to clinical pharmacy services in a pharmacist-physician covisit model compared to a referrals-based model. METHODS: A retrospective chart review was completed for patients who were seen by physicians on pre-specified half-days of clinic before and after implementation of the covisit model. Covisit model half-days between June 29, 2018 and September 30, 2018 and matched half-days from 2015 were included. Charts were reviewed to determine if patients scheduled to see the physician would benefit from clinical pharmacy services, including being seen for chronic disease management, eligible for a Medicare Annual Wellness Visit (AWV), prescribed medications that required counseling, had an adverse medication-related event, or had adherence concerns. Those eligible for clinical pharmacy services were further reviewed to determine if the patient interacted with a pharmacist within three months of their visit. RESULTS: Prior to implementation of the covisit model, 123 patient visits were completed on the pre-specified half-days. Of these, 61 patients (49.6%) were deemed eligible for clinical pharmacy services. In the covisit model, 149 patients were seen by the physician, of which 69 patients (46%) were eligible for clinical pharmacy services. More patients in the covisit cohort went on to interact with a pharmacist (56 patients, 81% vs. 10 patients, 16%, adjusted OR = 32.98, 95% CI [8.89-122.39]). The most common reasons patients were identified for clinical pharmacy services were eligibility for AWV, hypertension, and diabetes. CONCLUSIONS: A pharmacist-physician covisit model significantly increased accessibility to clinical pharmacy services compared to a referrals-based model.

Use of inhaled imipenem/cilastatin in pediatric patients with cystic fibrosis: A case series.

Mycobacterium abscessus is a rapidly-growing, virulent, non-tuberculous mycobacterium that causes progressive inflammatory lung damage and significant decline in lung functionin patients with cystic fibrosis. M. abscessus complex pulmonary infections are notoriously difficult to treat, and while many antibiotics are approved for children, drug allergies or intolerances can prohibit their use. Intravenous imipenem/cilastatin is among the preferred antibiotics for treatment of M. abscessus, however, its use may result in systemic toxicities including hepatic injury and gastrointestinal effects. Case reports document the successful use of inhaled imipenem/cilastatin in adult cystic fibrosis and non- cystic fibrosis patients with non- M. abscessus pulmonary infections. To our knowledge, similar evidence does not exist for pediatric patients. In this case series, we describe two pediatric patients with cystic fibrosis and previous intolerance or lack of response to standard therapies who received inhaled imipenem/cilastatin for the treatment of chronic M. abscessus infection.