Review of Best Practices for Diversity, Equity, and Inclusion Committees Within Colleges of Pharmacy.

Objective. To provide a review of best practices for diversity, equity, and inclusion (DEI) committees at United States colleges of pharmacy.Findings. In colleges of pharmacy, DEI committees can play a crucial role in promoting a culture change to ensure pharmacy graduates are equipped to provide equitable and representative care for the patients they serve. There is limited literature available on DEI committee composition, roles, and responsibilities, and their place within a college of pharmacy's organizational structure. A commitment to DEI should be part of the college's strategic plan and embedded and supported at all levels of the college and university to ensure success of DEI-related strategic initiatives. For a DEI committee to be effective, its composition should be intentional to include change agents, campus leaders, and members who are passionate and knowledgeable to execute the DEI goals. For sustainable change, involvement of the entire learning community and an organizational culture change is also important. Thus, DEI committees need to establish active bidirectional collaborations and communication with all key committees, offices, community leaders, and alumni to implement diversity goals.Summary. The DEI committee's established place in the organizational structure of the college is essential to ensure fair and appropriate representation of the community it serves. A clearly defined DEI committee with committee composition, roles, responsibilities, and its association with all constituents of the college and community can help achieve its intended strategic goals.

Rethinking the Pharmacy Workforce Crisis by Exploring Unconventional and Emerging Career Pathways and Training.

Given the limited availability of conventional pharmacy positions, pharmacy programs face a challenge in ensuring that all graduates obtain jobs that fulfill their goals and ambitions. Thus, it is imperative to explore and discuss unconventional but promising positions, specifically regarding their availability and needs. In exploring these positions, it is important to recognize technical and nontechnical skill sets that pharmacy graduates possess at graduation, identify unique pathways to help students explore job alternatives, and educate faculty and students about employment opportunities beyond the traditional setting if desired or necessary. Students must become aware of the opportunities that exist in both conventional (pharmacist clinician) and unconventional (pharmacist innovator) pharmacy careers and be able to articulate the translational skills from their training. Pharmacy programs and faculty can better support students by fostering the development and marketing of their skills.

Administration and Evaluation of the American Association of Colleges of Pharmacy Curriculum Quality Surveys in Pharmacy Schools.

Objective. To evaluate how pharmacy programs administer and evaluate American Association of Colleges of Pharmacy (AACP) curriculum quality perception surveys for continuous quality improvement, and to compare usage across the academy to the Principles of Good Use: AACP Quality Perception Surveys document.Methods. A 27-item survey instrument examining how schools used the curriculum quality survey was created and administered between March and June 2019 to assessment contacts of accredited schools and colleges of pharmacy. Descriptive statistics were performed for each survey item.Results. Of the 140 programs invited to participate, 88 (62.8%) responded. Curriculum quality survey data were triangulated with additional existing data (39.8%) or additional data sources were collected for triangulation with the survey data (54.5%). Programs reported on modifications made in the following areas: curriculum (85.2%), communication (75.0%), student services (68.2%), policy and process (61.4%), and professional development (53.4%). Most programs reported the assessment lead was responsible for oversight of the curriculum quality survey.Conclusion. Of respondents, 66% were familiar with the AACP Principles of Good Use document, and results indicate that institutions are generally following the recommendations. Survey analysis revealed that a significant number of programs are utilizing curriculum quality survey data for making meaningful programmatic improvements. Future work should center on further development of best practices for schools and colleges of pharmacy to effectively use the CQS data for continuous quality improvement.

Repurposing Bedaquiline for Effective Non-Small Cell Lung Cancer (NSCLC) Therapy as Inhalable Cyclodextrin-Based Molecular Inclusion Complexes.

There is growing evidence that repurposed drugs demonstrate excellent efficacy against many cancers, while facilitating accelerated drug development process. In this study, bedaquiline (BDQ), an FDA approved anti-mycobacterial agent, was repurposed and an inhalable cyclodextrin complex formulation was developed to explore its anti-cancer activity in non-small cell lung cancer (NSCLC). A sulfobutyl ether derivative of ß-cyclodextrin (SBE-ß-CD) was selected based on phase solubility studies and molecular modeling to prepare an inclusion complex of BDQ and cyclodextrin. Aqueous solubility of BDQ was increased by 2.8 × 103-fold after complexation with SBE-ß-CD, as compared to its intrinsic solubility. Solid-state characterization studies confirmed the successful incorporation of BDQ in the SBE-ß-CD cavity. In vitro lung deposition study results demonstrated excellent inhalable properties (mass median aerodynamic diameter: 2.9 ± 0.6 µm (<5 µm) and fine particle fraction: 83.3 ± 3.8%) of BDQ-CD complex. Accelerated stability studies showed BDQ-CD complex to be stable up to 3 weeks. From cytotoxicity studies, a slight enhancement in the anti-cancer efficacy was observed with BDQ-cyclodextrin complex, compared to BDQ alone in H1299 cell line. The IC50 values for BDQ and BDQ-CD complex were found to be ~40 µM in case of H1299 cell line at 72 h, whereas BDQ/BDQ-CD were not found to be cytotoxic up to concentrations of 50 µM in A549 cell line. Taken together, BDQ-CD complex offers a promising inhalation strategy with efficient lung deposition and cytotoxicity for NSCLC treatment.

Identification of potential binding pocket on viral oncoprotein HPV16 E6: a promising anti-cancer target for small molecule drug discovery.

BACKGROUND: Several human cancers, especially cervical cancer are caused by the infection of high risk strains of human papillomaviruses (HPV), notably HPV16. It is implicated that the oncoprotein E6 expressed from HPV, is inhibiting the apoptotic pathway by binding to adaptor molecule FADD (Fas-associated death domain). Inhibiting E6 interactions with FADD could provide a promising treatment for cervical cancer. There are few small molecules reported to inhibit such interactions. However, the FADD binding site information on the HPV E6 is not currently available. This binding site information may provide an opportunity to design new small molecule inhibitors to treat E6 mediated cancers. In this study we report the possible binding pocket on HPV16 E6 oncoprotein by using activity data of reported inhibitors through a stepwise molecular modeling approach. RESULTS: Blind docking and removing duplicates followed by visual inspection to determine ligand-receptor interactions provided 68 possible binding sites on the E6 protein. Individual docking of all known inhibitors lead to the identification of 28 pockets having some kind of correlation with their activity data. It was also observed that several of these pockets overlapped with each other, having some amino acids in common. Amino acids Leu50 and Cys51 were identified as key E6 residues for high affinity ligand binding which are seen in most of these pockets. In most cases, ligands demonstrated a hydrogen bond interaction with Cys51. Ala61, Arg131 and Gln107 were also frequently observed showing interactions among these pockets. A few amino acids unique to each ligand were also identified representing additional interactions at the receptor site. CONCLUSIONS: After determining receptor-ligand interactions between E6 oncoprotein and the six known inhibitors, the amino acids Cys51, Leu50, Arg102, Arg131, Leu67, Val62, and Gln107 were identified to have importance in E6 inhibition. It was generally observed that Leu50 and Cys51 are necessary for high binding affinity with Cys51 being essential for hydrogen bonding. This study identified a potential binding pocket for the E6 inhibitors. Identification of the ligand binding pocket helps to design novel inhibitors of HPV16 E6 oncoprotein as a promising treatment for cervical cancer.

A Review of Strategies for Designing, Administering, and Using Student Ratings of Instruction.

Objective. To review and recommend strategies for utilizing student ratings of instruction (course and instructor) including considerations regarding design, administration, and use and interpretation of results. Findings. Improving course delivery and pedagogy using student ratings of instruction requires programs to design evaluation instruments that are aligned with the following good, scholarly teaching criteria: offer 10-20 rating scale questions and at least one written response question, ensure that students understand what the questions are asking, use a standardized form for evaluating all faculty members, allow for additional tailored questions to be added to the form, and employ a four- or five-point rating scale with a "not applicable" option. When administering evaluations, programs should limit the number of faculty members evaluated to those teaching greater than or equal to five clock hours of lecture or schedule evaluations based on academic rank; use an online course evaluation tool; randomly select students to participate; offer the evaluation at the end of the term (and/or midpoint for team taught classes); offer the evaluation during scheduled class time; and allow for voluntary, anonymous student participation. Finally, programs should create an assessment plan that outlines the results' release timeline, a list of who will receive result summaries, and how the results will be used. Programs should also encourage faculty reflection, offer mentoring in results interpretation, coach faculty members to summarize and quantify comments and longitudinally track results using tables, and create an accountability action plan to address deficiencies. Summary. In order to better ensure that student ratings of instruction are used to improve teaching, colleges and schools should adopt intentional design, structured administration processes, and transparent reporting of results.

Nintedanib-cyclodextrin complex to improve bio-activity and intestinal permeability.

Cyclodextrin complex of nintedanib was prepared aiming for increased bio-activity and improved transport across intestinal membrane with reduced p-glycoprotein (p-gp) efflux. Based on preliminary phase solubility studies and molecular modeling, sulfobutyl ether derivative of ß-cyclodextrin (SBE-ß-CD, Captisol®) was selected to prepare inclusion complex. Complexation was confirmed using FTIR, 1H NMR, DSC, and XRD. Bioactivity of the formed complex was tested using lung fibroblast cells, WI-38 for anti-proliferative activity and effect on collagen deposition and cells migration. In-vitro permeability studies were performed using epiIntestinal tissue model to assess the effect of complexation on transport and p-gp efflux. Results of the study demonstrated that cyclodextrin complexation increased stability of nintedanib in PBS (pH 7.4) and simulated intestinal fluid (SIF). Further, bioactivity of nintedanib also improved. Interestingly, complexation has increased transport of nintedanib across intestinal membrane and reduced efflux ratio, suggesting the role of cyclodextrin complexation in modulating p-gp efflux.

Recent advances in the discovery of small-molecule inhibitors of HIV-1 integrase.

AIDS caused by the infection of HIV is a prevalent problem today. Rapid development of drug resistance to existing drug classes has called for the discovery of new targets. Within the three major enzymes (i.e., HIV-1 protease, HIV-1 reverse transcriptase and HIV-1 integrase [IN]) of the viral replication cycle, HIV-1 IN has been of particular interest due to the absence of human cellular homolog. HIV-1 IN catalyzes the integration of viral genetic material with the host genome, a key step in the viral replication process. Several novel classes of HIV IN inhibitors have been explored by targeting different sites on the enzyme. This review strives to provide readers with updates on the recent developments of HIV-1 IN inhibitors.

Development and validation of a high-performance liquid chromatography method for the quantification of talazoparib in rat plasma: Application to plasma protein binding studies.

A sensitive and selective RP-HPLC method has been developed and validated for the quantification of a highly potent poly ADP ribose polymerase inhibitor talazoparib (TZP) in rat plasma. Chromatographic separation was performed with isocratic elution method. Absorbance for TZP was measured with a UV detector (SPD-20A UV-vis) at a λmax of 227 nm. Protein precipitation was used to extract the drug from plasma samples using methanol-acetonitrile (65:35) as the precipitating solvent. The method proved to be sensitive and reproducible over a 100-2000 ng/mL linearity range with a lower limit of quantification (LLQC) of 100 ng/mL. TZP recovery was found to be >85%. Following analytical method development and validation, it was successfully employed to determine the plasma protein binding of TZP. TZP has a high level of protein binding in rat plasma (95.76 ± 0.38%) as determined by dialysis method.

Structured academic discussions through an online education-specific platform to improve Pharm.D. students learning outcomes.

OBJECTIVE: To facilitate active academic discussions using an online, education-centered platform and reinforce concepts, in order to improve overall course outcomes. MATERIALS AND METHODS: A third year integrated pharmacotherapy course was enrolled on an online searchable platform, Piazza®, to facilitate academic discussions. Students could ask, answer, and explore content, and build on submitted answers in wiki style in collaboration. Instructor posted learning objectives, endorsed student responses with correct answers and led follow-up discussions. Review sessions were conducted on this platform before all major exams. A student t-test was used to compare class performance with those of previous years. RESULTS: In a post-activity qualitative survey, most students appreciated the less stressful, online interaction with peers and faculty. For 15 medicinal chemistry course hours, there were 83 posts on Piazza® with 303 total contributions, 107 student responses, and 546min of group discussion time. 94% of questions received student responses and 89% of those were endorsed by the instructor. Students enjoyed pre-exam discussions, organization of the page, and reinforcing material on complex learning objectives. This discussion forum fostered personal exploration of content by the students, which led to better performance on examinations. CONCLUSIONS: Involving the use of an online, education-centered platform for student discussions was an effective means of increasing class engagement with the course material. Student performance on exams was significantly improved in both cohorts that utilized active learning compared to the cohort without active learning (p=0.001 and p= 0.002 respectively). Piazza® can be utilized for any course and across disciplines.

Advances in treatment of pulmonary arterial hypertension: patent review.

INTRODUCTION: Current therapeutic approaches for pulmonary arterial hypertension (PAH) commonly include use of prostacyclins, endothelin pathway antagonists or NO (nitric oxide) pathway modulators. These agents are non-specific and suffer from several important shortcomings including short half-lives, invasive routes of administration, higher dose and frequency requirements, and several dose-related systemic side effects. Hence, discovery of novel agents with improved therapeutic efficacy with respect to survival benefits and the development of non-invasive routes of administration are in critical need. Current research aimed at developing more selective therapies for PAH are focused both on agents acting on novel molecular targets, as well as, novel compounds acting on conventional pathways with improved characteristics. Area covered: The present review covers recently filed (issued/application) patents (2010-2016) describing novel agents acting on investigational targets as well as novel compounds with improved characteristics acting on established targets. Patents describing combinations of conventional and investigational compounds are also discussed. Expert opinion: PAH has recently been considered as cancer-like disease with over-proliferation of pulmonary arterial smooth muscle cells and endothelial cells. New cellular and molecular biological advances have revealed novel target/pathways involved in the pathogenesis and progression of PAH. Thus, discovery of agents that act on these novel pathways provides a promising avenue of research for improving therapeutic approaches for PAH.

Synthesis and biological evaluation of indole-2-carboxamides bearing photoactivatable functionalities as novel allosteric modulators for the cannabinoid CB1 receptor.

5-Chloro-3-ethyl-N-(4-(piperidin-1-yl)phenethyl)-1H-indole-2-carboxamide (ORG27569, 1) is a prototypical allosteric modulator for the cannabinoid CB1 receptor. Based on this indole-2-carboxamide scaffold, we designed and synthesized novel CB1 allosteric modulators that possess photoactivatable functionalities, which include benzophenone, phenyl azide, aliphatic azide and phenyltrifluoromethyldiazrine. To assess their allosteric effects, the dissociation constant (KB) and allosteric binding cooperativity factor (α) were determined and compared to their parent compounds. Within this series, benzophenone-containing compounds 26 and 27, phenylazide-containing compound 28, and the aliphatic azide containing compound 36b showed allosteric binding parameters (KB and α) comparable to their parent compound 1, 7, 8, and 9, respectively. We further assessed these modulators for their impact on G-protein coupling activity. Interestingly, these compounds exhibited negative allosteric modulator properties in a manner similar to their parent compounds, which antagonize agonist-induced G-protein coupling. These novel CB1 allosteric modulators, possessing photoactivatable functionalities, provide valuable tools for future photo-affinity labeling and mapping the CB1 allosteric binding site(s).

SN-38-cyclodextrin complexation and its influence on the solubility, stability, and in vitro anticancer activity against ovarian cancer.

SN-38, an active metabolite of irinotecan, is up to 1,000-fold more potent than irinotecan. But the clinical use of SN-38 is limited by its extreme hydrophobicity and instability at physiological pH. To enhance solubility and stability, SN-38 was complexed with different cyclodextrins (CDs), namely, sodium sulfobutylether ß-cyclodextrin (SBEßCD), hydroxypropyl ß-cyclodextrin, randomly methylated ß-cyclodextrin, and methyl ß-cyclodextrin, and their influence on SN-38 solubility, stability, and in vitro cytotoxicity was studied against ovarian cancer cell lines (A2780 and 2008). Phase solubility studies were conducted to understand the pattern of SN-38 solubilization. SN-38-ßCD complexes were characterized by differential scanning calorimetry (DSC), X-ray powder diffraction analysis (XRPD), and Fourier transform infrared (FTIR). Stability of SN-38-SBEßCD complex in pH 7.4 phosphate-buffered saline was evaluated and compared against free SN-38. Phase solubility studies revealed that SN-38 solubility increased linearly as a function of CD concentration and the linearity was characteristic of an AP-type system. Aqueous solubility of SN-38 was enhanced by about 30-1,400 times by CD complexation. DSC, XRPD, and FTIR studies confirmed the formation of inclusion complexes, and stability studies revealed that cyclodextrin complexation significantly increased the hydrolytic stability of SN-38 at physiological pH 7.4. Cytotoxicity of SN-38-SBEßCD complex was significantly higher than SN-38 and irinotecan in both A2780 and 2008 cell lines. Results suggest that SBEßCD encapsulated SN-38 deep into the cavity forming stable inclusion complex and as a result increased the solubility, stability, and cytotoxicity of SN-38. It may be concluded that preparation of inclusion complexes with SBEßCD is a suitable approach to overcome the solubility and stability problems of SN-38 for future clinical applications.

Structure-activity relationship study of indole-2-carboxamides identifies a potent allosteric modulator for the cannabinoid receptor 1 (CB1).

The cannabinoid CB1 receptor is involved in complex physiological functions. The discovery of CB1 allosteric modulators generates new opportunities for drug discovery targeting the pharmacologically important CB1 receptor. 5-Chloro-3-ethyl-N-(4-(piperidin-1-yl)phenethyl)-1H-indole-2-carboxamide (ORG27569; 1) represents a new class of indole-2-carboxamides that exhibit allostery of CB1. To better understand the SAR, a group of indole-2-carboxamide analogues were synthesized and assessed for allostery of the CB1 receptor. We found that within the structure of indole-2-carboxamides, the presence of the indole ring is preferred for maintaining the modulator's high binding affinity for the allosteric site but not for generating allostery on the orthosteric site. However, the C3 substituents of the indole-2-carboxamides significantly impact the allostery of the ligand. A robust CB1 allosteric modulator 5-chloro-N-(4-(dimethylamino)phenethyl)-3-pentyl-1H-indole-2-carboxamide (11j) was identified. It showed an equilibrium dissociation constant (KB) of 167.3 nM with a markedly high binding cooperativity factor (α = 16.55) and potent antagonism of agonist-induced GTPγS binding.

An assessment model for multidisciplinary, team-taught integrated pharmacy courses.

OBJECTIVE: To design and implement an assessment model to effectively deliver integrated multidisciplinary team-taught pharmacy courses. DESIGN: An assessment model was developed for an integrated pharmacotherapeutics course that focused on writing detailed learning objectives and matching them to examination questions. Qualitative assessment of learning objectives, course-embedded quantitative assessment, and objective assessments of examinations by subdiscipline were performed. ASSESSMENT: This model was assessed through course evaluations, faculty and course coordinator perceptions, and faculty and student focus groups, which provided data that facilitated effective integration and identified gaps and overlaps in content. The assessment of the examinations by discipline and the embedded quantitative assessment results identified previously unassessed and poorly performing objectives. Students believed the course contributed significantly to their professional growth and that it was one of the best-integrated courses, based in part on the improved teaching methods. CONCLUSIONS: A systematic assessment model that was developed for the effective delivery of multidisciplinary team-taught courses can be standardized and delivered despite changes in instructors for subsequent course offerings.

An active-learning assignment requiring pharmacy students to write medicinal chemistry examination questions.

OBJECTIVES: To implement and assess the effectiveness of an assignment requiring doctor of pharmacy (PharmD) students to write examination questions for the medicinal chemistry sections of a pharmacotherapeutics course. DESIGN: Students were divided into groups of 5-6 and given detailed instructions and grading rubrics for writing multiple-choice examination questions on medicinal chemistry topics. The compiled student-written questions for each examination were provided to the entire class as a study aid. Approximately 5% of the student-written questions were used in course examinations. ASSESSMENT: Student appreciation of and performance in the medicinal chemistry portion of the course was significantly better than that of the previous year's class. Also, students' responses on a qualitative survey instrument indicated that the assignment provided students' guidance on which concepts to focus on, helped them retain knowledge better, and fostered personal exploration of the content, which led to better performance on examinations. CONCLUSION: Adding an active-learning assignment in which students write examination questions for the medicinal chemistry portion of a pharmacotherapeutics course was an effective means of increasing students engagement in the class and knowledge of the course material.

A multi-instructor, team-based, active-learning exercise to integrate basic and clinical sciences content.

OBJECTIVES: To introduce a multiple-instructor, team-based, active-learning exercise to promote the integration of basic sciences (pathophysiology, pharmacology, and medicinal chemistry) and clinical sciences in a doctor of pharmacy curriculum. DESIGN: A team-based learning activity that involved pre-class reading assignments, individual-and team-answered multiple-choice questions, and evaluation and discussion of a clinical case, was designed, implemented, and moderated by 3 faculty members from the pharmaceutical sciences and pharmacy practice departments. ASSESSMENT: Student performance was assessed using a multiple-choice examination, an individual readiness assurance test (IRAT), a team readiness assurance test (TRAT), and a subjective, objective, assessment, and plan (SOAP) note. Student attitudes were assessed using a pre- and post-exercise survey instrument. Students' understanding of possible correct treatment strategies for depression improved. Students were appreciative of this true integration of basic sciences knowledge in a pharmacotherapy course and to have faculty members from both disciplines present to answer questions. Mean student score on the on depression module for the examination was 80.4%, indicating mastery of the content. CONCLUSIONS: An exercise led by multiple instructors improved student perceptions of the importance of team-based teaching. Integrated teaching and learning may be achieved when instructors from multiple disciplines work together in the classroom using proven team-based, active-learning exercises.

Methadone toxicity due to smoking cessation--a case report on the drug-drug interaction involving cytochrome P450 isoenzyme 1A2.

OBJECTIVE: To report the potential clinically significant pharmacokinetic interaction that may result from smoking cessation in patients on methadone maintenance therapy. CASE SUMMARY: A 46-year-old white man was admitted to the step-down intensive care unit with decreased respirations and altered mental status related to methadone toxicity. The patient had been on a stable dose of methadone for chronic back pain, and he reported a 1 pack per day, 33-year history of cigarette smoking. After methadone was held for 3 days, his mental status improved. It was later revealed that he had initiated smoking cessation. He was discharged home on a reduced dose of methadone with no further complications. DISCUSSION: While the potential for toxicity exists for patients who are maintained on methadone and decrease the number of cigarettes they smoke, to our knowledge, there is no recent peer-reviewed literature on this interaction. Methadone is a synthetic opioid primarily metabolized by CYP3A4 and, to a lesser degree, by other isoenzymes, including CYP1A2. Polycyclic aromatic hydrocarbons found in tobacco smoke are known CYP1A2 inducers. Decreased intake of cigarette smoke can lead to a reduction in methadone metabolism, resulting in higher serum concentrations. Our case is an example of methadone toxicity secondary to smoking cessation in a patient on methadone maintenance therapy. An objective causality assessment based on the Horn Drug Interaction Probability Scale revealed the interaction to be probable. CONCLUSIONS: Patients on methadone should be monitored for signs of methadone toxicity upon the start of smoking cessation, and the dose of methadone should be adjusted accordingly. Additional information and reports cautioning clinicians and patients about this potential interaction would be beneficial.