Development of an innovative partnership between a health-system department of pharmacy and external community pharmacies.

PURPOSE: Our organization implemented a health-system pharmacy/community pharmacy transitions of care (TOC) program, developing a scalable model to improve care transitions from the health system to the community setting for shared patients. SUMMARY: In this report, we describe our organization's experiences in taking a purposeful approach to building and pilot testing a partnership between our department of pharmacy and 14 community pharmacies within a larger statewide network to improve TOC across care settings. We have been successful in partnering with our electronic health record (EHR) vendor to enhance access capabilities to allow for documentation by community pharmacists (external to the organization) to be included in the patient record as a note. The goal of the partnership with community pharmacies is to elevate TOC for patients, identify and resolve medication therapy problems that may occur post discharge and lead to poor outcomes, and improve continuity of care across practice settings. CONCLUSION: Our department of pharmacy has led a successful initiative to promote collaboration with local external community pharmacies. This program has led to innovative advancements in EHR capabilities, promoting transparency in the documentation of pharmacy services and making this documentation visible to all care team members.

Effectiveness and impact of a structured research approach for health-system pharmacy administration and leadership residents.

PURPOSE: Required competency areas, goals, and objectives for both postgraduate year 1 (PGY1) pharmacy residencies and postgraduate year 2 (PGY2) health-system pharmacy administration and leadership (HSPAL) residencies indicate the importance of research in the residency program by specifying it as a required part of the training process. Research is critical in the field of health-system pharmacy administration, which is built upon the principles of evaluation and assessment, ensuring that all activities implemented in an organization are evaluated through data collection and assessment to determine their impact. Additionally, the research structure provides residents the opportunity to share research broadly, and it also provides the platform for other institutions to implement successful ideas of interest to them. SUMMARY: This article describes the impact of having a structured, publication-focused research program in an HSPAL residency. The research process has provided follow-up projects (n = 7) and grant participation (n = 6). Additionally, the process has yielded a 66% publication rate, with 21 of 32 thesis substitutes published in various journals. The department of pharmacy at the residency site has noticed that the continued refinement, scoping, and robust methodologies of projects have been essential to their impact in the literature and in dissemination of the accumulated body of knowledge. CONCLUSION: A structured residency research program has provided direction to HSPAL residents and ensured successful scoping and completion of their research. Intentionality in this aspect has provided HSPAL residents with opportunities for publications, grants, and strong research experiences. Overall, the department of pharmacy has been positively impacted through implementation of services that were evaluated through a structured HSPAL pharmacy residency research program.

Punishments and the dominance identity in networks.

In this study, we examine the effects of the structure of a network, the dominance identity of the actors, and the actors' ability to reward or punish on the use of punishment and the development of social bonds in a network. As expected, we find that peripheral rather than central actors in a network use punishment more, as do those with a high dominance identity. We also find that persons use punishment to increase or decrease their perceived level of dominance when their dominance identity is not verified. However, the patterns of interaction that develop in the network are an interactive function of network position, actor's dominance identity, and punishment use. We discuss how the social psychological drive to control one's identity interacts with social structural factors in the network to create different cultures of dyadic interaction.

Status and competitive choice.

In this paper, we extend the logic of existing sociological theory on status to explain how status processes can inform selection in competitive choice situations. We argue that in the absence of knowledge about the specific abilities of others and assuming a desire to win, when given the opportunity to "pick their battles," people will draw on overt status differences as a basis for selecting a competitor from a pool of possible competitors. Results from three studies indicate that, as predicted, status differences affect competitor selection, with individuals choosing to compete against those who are relatively lower status based on diffuse characteristics. Moreover, consistent with expectation state theories, results from two studies show that the expectations that people form for their potential competitors based on status differences mediate this relationship. We conclude by discussing the implications of this research.

Impact of an innovative partnership in patient care between an academic medical center department of pharmacy and a school of pharmacy.

PURPOSE: Pharmacy departments and schools of pharmacy have long held professional affiliations. However, the success of each entity is often not interdependent and aligned. In 2010, our institutions found ourselves in a position where the complementary motivations of each aligned to support a more meaningful and committed engagement, leading to the development of the Partnership in Patient Care. The impact of the partnership was evaluated 7 years postimplementation, and both the successes realized and the lessons learned are described. SUMMARY: The partnership provided many advantages to our pharmacy department and the school of pharmacy. This initial iteration of the partnership was a strong proof of concept that an intentional approach to the relationship between a school of pharmacy and a pharmacy department can lead to substantive improvements in a wide array of meaningful outcomes. We experienced an increase in the number of student rotation months completed, growth in the American Society of Health-System Pharmacists-accredited residency programs, and enhanced clinical services. However, the partnership was not without challenges. For instance, lack of a formalized tracking method made certain outcomes difficult to track. CONCLUSION: The purposeful establishment of the Partnership in Patient Care, built on the needs of a school of pharmacy and an academic medical center pharmacy department, allowed our institutions to develop an intertwined mission and vision. Over the initial years of the partnership, many successes were realized and lessons were learned. Both the successes and the challenges are serving as the foundation for future iterations of the partnership.

Implementation of the flipped residency research model to enhance residency research training.

PURPOSE: The attainment of fundamental research skills to create and disseminate new knowledge is imperative for the advancement of pharmacy practice. Research training is an important component of postgraduate residency training; however, the traditional model of performing residency research has several limitations that have hindered the ability of residents to complete high-quality research projects. Therefore, our institution developed and implemented the flipped residency research model with the 2013-2014 pharmacy practice residency class. SUMMARY: The flipped residency research model modifies the research timeline to better align research activities with residents' abilities at specific time points during the year. In the 4 years following implementation of the flipped residency research model, our institution found improvements in a number of areas pertaining to the research process compared with an evaluation of the 7 years prior to implementation. A decrease in the number of reviews required from institutional review boards was observed, resulting in improved institutional review board efficiency. The flipped residency research model also addressed limitations surrounding manuscript development and submission, as demonstrated by an improved publication rate. Additionally, residents who participated in the flipped residency research model self-reported increased comfort with research-related abilities associated with study design, implementation, manuscript development and submission, and biostatistics. CONCLUSION: The modified research timeline of the flipped residency research model better aligns research activities with resident experiences and abilities. This realignment has translated to demonstrable impact in the success of residency projects and dissemination of results. Research is needed to investigate the impact of the flipped residency research model on longer term scholarly success.

Utilizing Native Directing Groups: Mechanistic Understanding of a Direct Arylation Leads to Formation of Tetracyclic Heterocycles via Tandem Intermolecular, Intramolecular C-H Activation.

A mechanistic study on a direct arylation using a native picolylamine directing group is reported. Kinetic studies determined the concentration dependence of substrates and catalysts, as well as catalyst degradation, which led to the development of a new set of reaction conditions capable of affording a robust kinetic profile. During reaction optimization, a small impurity was observed, which was determined to be a dual C-H activation product. A second set of conditions were found to flip the selectivity of the C-H activation to form this tetracycle in high yield. A catalytic cycle is proposed for the intermolecular/intramolecular C-H activation pathway.

The fairness identity and the emergence of inequality.

Social exchange theories explain how differences in structural power can generate inequalities in exchange networks. We argue here that even in the absence of structural power differences, inequality can emerge out of the identity process. We posit that when structurally equivalent actors are uncertain about the resource levels available for distribution, different levels of the fairness identity and responses to identity non-verification will influence how they negotiate for resources. Results from an experiment that varies the fairness identity level and the identity verification of actors in two different equal power exchange networks confirm this. Absent structural power differences, the level of the fairness identity, identity non-verification, and structure of the network mutually influence the distribution of resources such that some dyads earn as much as two and a half times more than others. We discuss our findings as they pertain to unearthing the processes by which group inequalities arise and persist.

Utilizing Native Directing Groups: Synthesis of a Selective IKur Inhibitor, BMS-919373, via a Regioselective C-H Arylation.

BMS-919373 is a highly functionalized quinazoline under investigation as a selective, potent IKur current blocker. By utilizing the aminomethylpyridine side chain at C-4, a selective C-H functionalization at C-5 was invented, enabling the efficient synthesis of this molecule. The strategy of leveraging this inherent directing group allowed the synthesis of this complex heterocycle in only six steps from commodity chemicals. The scope of the C-H activation was further investigated, and the generality of the transformation across a series of bicyclic aromatic heterocycles was explored.

Synthesis of Selective Estrogen Receptor Degrader GDC-0810 via Stereocontrolled Assembly of a Tetrasubstituted All-Carbon Olefin.

We report an efficient synthesis of GDC-0810 on the basis of a sequence involving a highly stereoselective lithium tert-butoxide-mediated enolization-tosylation (≥95:5 E: Z) and a Pd-catalyzed Suzuki-Miyaura cross-coupling as key steps. Global deprotection, pyrrolidine salt formation, and final active pharmaceutical ingredient (API) form control/isolation produced GDC-0810 free acid in a 40% overall yield with >99.0% purity as ascertained by HPLC analysis.

Improved Adherence Rates and Clinical Outcomes of an Integrated, Closed-Loop, Pharmacist-Led Oral Chemotherapy Management Program.

PURPOSE: To address the growing use of oral anticancer therapy, an integrated, closed-loop, pharmacist-led oral chemotherapy management program was created within an academic medical center. METHODS: An integrated, closed-loop, pharmacy-led oral chemotherapy management program was established. From September 2014 until June 2015, demographic information, rates of adherence, patient understanding of treatment, pharmacist interventions, patient and provider satisfaction, and molecular response rates in patients with chronic myeloid leukemia (CML) were collected. RESULTS: After full implementation, 107 patients were enrolled in our oral chemotherapy management program from September 2014 until June 2015. All patients were educated before starting oral chemotherapy, and using pre- and postassessment tests, comprehension of oral chemotherapy treatment increased from 43% to 95%. Patient-reported adherence was 86% and 94.7% for the GI/breast and malignant hematology patient populations, respectively, and these were validated with medication possession ratio, revealing adherence rates of 85% and 93.9% for the GI/breast and malignant hematology patient populations, respectively. A total of 350 encounters with a clinical pharmacist and 318 adverse effects were reported, which led to 235 interventions. This program led to a higher major molecular response rate (83%) in our CML population compared with published clinical trials (average major molecular response rates, 40% and 60% with 1- and 2-year follow-up, respectively). CONCLUSION: An innovative model was developed and resulted in improved patient knowledge regarding oral chemotherapy, improved adherence rates that exceeded nationally established thresholds, and superior major molecular response outcomes for patients with CML compared with published literature. As a result, this model has produced the gold standard in managing patients receiving oral chemotherapy.

Practical strategies when using a stable isotope labeled microtracer for absolute bioavailability assessment: A case study of a high oral dose clinical candidate GDC-0810.

The pH labile metabolite, hydrophobicity, high oral dose and systematic exposure of GDC-0810 posed tremendous challenges to develop a LC-MS method for a stable isotope labeled aBA study. In this study, we explored practical solutions to balance stability and sensitivity and to cope with the impact of high Cp.o. to Ci.v. ratio on the labeling selection and assay dynamic range. A [13C9] GDC-0810 was synthesized to minimize the isotopic interference between PO dose, internal standard and I.V. microtracer. A highly sensitive LC-MS assay was validated for quantitation of [13C9] GDC-0810 from 5 to 1250 pg/mL. The optimized method was applied to a proof of concept cynomolgus monkey aBA study and the bioavailability calculated using microtracer dosing and regular dosing were similar to each other.

Synthesis of a Selective Estrogen Receptor Degrader via a Stereospecific Elimination Approach.

An efficient synthesis of a selective estrogen receptor degrader, GDC-0810, bearing a challenging stereodefined (E)-tetrasubstituted all-carbon olefin core, is reported. The described synthetic route involves a highly diastereoselective addition of an arylmagnesium reagent 3a to ketone 4, yielding the key tertiary alcohol 2a in >99:1 dr. The corresponding tert-butyl carbonate derivative was identified among other leaving groups to provide the desired olefin geometry in a 98:2 E/Z ratio via a concerted elimination. A four-step telescoped process was then developed starting from the tertiary alcohol 2a to produce GDC-0810 API as a pyrrolidine salt in 70% yield.

Implementation of a longitudinal early immersion student pharmacist health system internship program.

PURPOSE: The initiation, implementation, and benefits of a longitudinal early immersion student pharmacist health system internship are described. EDUCATIONAL ACTIVITY: A two-year longitudinal internship experience was implemented to provide exposure into distributional operations, direct patient care activities, and health-system pharmacy administration. The intent of the program was to create an opportunity for student pharmacists to enhance the quality of their education with practical experience by immersing them early in their careers within the healthcare system. Early in their academic training the student interns were exposed to a broad range of services and programs while contributing longitudinally to the service line through quality improvement projects and distributional operations. The first year primarily focuses on distributional operations with direct patient care shadowing, while the second year targets intern involvement in hematology/oncology direct patient care activities. In this role, they are able to serve as pharmacist extenders. SUMMARY: Our comprehensive, longitudinal two-year health-system pharmacy internship program offers student pharmacists a unique early immersion experience that builds upon itself throughout their didactic training but is outside of the academic requirements. Students are exposed to distributional operations, direct patient care activities, and health system pharmacy administration prior to APPE rotations.

Implementation of an integrated pharmacy supply management strategy.

PURPOSE: Implementation of an integrated pharmacy supply management strategy is described. SUMMARY: In 2011, the formulary approval process and supply management for oncology medications were independent of each other at an oncology infusion center. Numerous nonformulary medications were kept on hand and reordered based on inventory levels that were established with inadequate usage information, while some formulary agents did not have on-hand inventory levels and had to be reordered on a patient-specific basis, which required paperwork and then a review by drug information staff per institutional policy. Because there was no true distinction in the ordering of formulary versus nonformulary oncology agents, the medical staff prescribed both in the same manner, leaving the pharmacy staff responsible for ensuring that enough quantities were on hand for many drugs, regardless of formulary status. Using supply chain management principles, a formal analysis of the on-hand inventory was performed. In addition, the formulary process for oncology drugs was restructured to align with how oncology drugs are managed for on-hand inventory levels. The alignment of these processes allowed the operation to have 1 supply strategy for the ambulatory oncology infusion center. As a result, inventory exhaustion rates were reduced by 70% and inventory turn rates improved by 78%. There was also significant time savings in the operational process streamlining, eliminating the rework and inefficiencies caused by an unclear process that was not fully captured in this assessment. CONCLUSION: Alignment of the formulary review process with inventory analyses that support supply management principles reduced inventory exhaustion while improving inventory turn rates.

Impact of Inpatient Automatic Therapeutic Substitutions on Postdischarge Medication Prescribing.

Background: Automatic therapeutic substitution (ATS) is the act of therapeutic interchange, in which patients are transitioned from a nonformulary preadmission medication to an equivalent formulary medication upon admission. ATS protocols are able to provide several benefits; however, if medications are unreconciled at the time of discharge, then use may lead to duplication or omission resulting in adverse outcomes. The objective was to assess the impact of preidentified ATS protocol use during admission on duplication and omission postdischarge. Methods: This study included adults who received a preidentified ATS upon admission. The primary outcome was the incidence of duplication or omission at the time of discharge. The secondary outcome was the incidence of duplication or omission at the time of discharge in moderate-to-high readmission risk patients with completed transitions of care (TOC) services compared with incomplete TOC services. Results: A total of 689 encounters were assessed for appropriate reconciliation, duplication, or omission at time of discharge. The incidence of duplication or omission at the time of discharge was 9% (n = 62). Of the 689 encounters, 287 were assessed for the secondary outcome. The rate of duplication or omission at the time of discharge was 10% (n = 19) in the complete TOC services group and 8% (n = 8) in the incomplete TOC services group (P = .6763). Conclusion: This study identified a high rate of appropriate reconciliation of ATS protocols at the time of discharge, which illustrates ATS protocols are a safe medication use management strategy if implemented as intended.

Asymmetric Synthesis of Akt Kinase Inhibitor Ipatasertib.

A highly efficient asymmetric synthesis of the Akt kinase inhibitor ipatasertib (1) is reported. The bicyclic pyrimidine 2 starting material was prepared via a nitrilase biocatalytic resolution, halogen-metal exchange/anionic cyclization, and a highly diastereoselective biocatalytic ketone reduction as key steps. The route also features a halide activated, Ru-catalyzed asymmetric hydrogenation of a vinylogous carbamic acid to produce α-aryl-ß-amino acid 3 in high yield and enantioselectivity. The API was assembled in a convergent manner through a late-stage amidation/deprotection/monohydrochloride salt formation sequence.