Practical Pharmacology of Methadone: A Long-acting Opioid.

Methadone is a naturally long-acting analgesic with unique pharmacodynamic and pharmacokinetic properties compared to other opioids, available now in India, to treat severe pain. It has the potential to dramatically relieve suffering among patients with serious illness who are living with persistent physical pain. However, clinicians must appreciate its unique pharmacologic properties and its use in clinical practice safely and effectively. The available formulation in India is a racemic mixture of the S- and R-enantiomers, and as such, it will have a propensity for drug-drug and drug-genetic interactions that can increase the risk of Torsades de Point and respiratory depression. Appropriate patient selection, careful dosing and thorough monitoring of methadone will mitigate these risks.

Development and validation of a performance-based palliative care assessment tool for student pharmacists.

INTRODUCTION: Integration of hospice and palliative care principles within pharmacy curricula is essential to fill the need of pharmacist training in this growing specialty. A formalized assessment tool to evaluate skill development does not exist for student pharmacists specific to palliative care. The objective of this study was to develop a valid and reliable, palliative care-focused, performance-based assessment tool for student pharmacists. METHODS: Eight academic palliative care (PC) pharmacists were recruited for the workgroup to perform domain development, validation, tool creation, and reliability testing for this performance-based assessment tool. Hospice and palliative care clinical pharmacist entrustable professional activities (EPAs) served as the framework. Content validity testing utilized content validity index and scale universal agreement (S-CVI/UA) to determine level of agreement for activities included in the tool. Student volunteers completed a standardized patient case and workgroup members served as raters during the reliability testing phase. Interrater reliability was measured through calculation of Fleiss Kappa scores for each activity. RESULTS: Out of 14 EPAs, nine were deemed "essential" to include in the tool. Thirty-four supporting activities for the nine essential EPAs were drafted. Two rounds of content validity testing were necessary to achieve S-CVI/UA of 0.9593. Consensus was reached from workgroup members for activities deemed necessary to include in the tool after questionnaire distribution utilizing a Fleiss Kappa cutoff >0.6. CONCLUSIONS: This validated tool will afford colleges and schools of pharmacy with PC curricula an opportunity to assess student achievement of PC-specific skills and evaluate curricular effectiveness.

Antibiotic stewardship in Indian palliative care: a single-center retrospective study.

Objective: Characterize antibiotic prescribing behaviors at an Indian palliative care center after the initiation of the Antibiotic Order Form (AOF): an antibiotic stewardship program involving a paper form to track antibiotic use and to provide prescription guidelines. Design: Retrospective chart review. Setting: Trivandrum Institute of Palliative Sciences (TIPS) is a palliative care organization in Kerala, India. Methods: Antibiotic prescription data and patient data were collected for adult patients treated at TIPS between January 1, 2017, and October 31, 2019. Descriptive statistics and a Zero-Inflated Poisson regression model were used to analyze antibiotic prescriptions. AOF completion and prescription concordance with institutional guidelines were also evaluated. Results: Out of 7,450 unique patients, 675 (9%) were prescribed 1,448 antibiotics. Age was the strongest factor in determining the number of antibiotic courses with each additional year of age decreasing the expected antibiotic prescription count by 2% per year. The most common antibiotics prescribed were topical metronidazole (44%) and penicillins (29%). Among patients who died, 5% were prescribed antibiotics within the final month of life. In total, 32% of antibiotic prescriptions were documented in AOFs, and 18% were concordant with all institutional antibiotic prescribing guidelines. Conclusions: This study is the first to analyze an antibiotic stewardship intervention in a palliative care setting within a low- and middle-income country. This retrospective study provides a benchmark of antibiotic use within Indian palliative care and highlights areas for future stewardship research including topical metronidazole use within palliative care and higher rates of antibiotic use among younger palliative care patients.

The AACP Academic Affairs Committee's Final 2022 Curricular Outcomes and Entrustable Professional Activities (COEPA) for Pharmacy Graduates to Replace 2013 CAPE and 2016 EPAs.

The American Association of Colleges of Pharmacy (AACP) Academic Affairs Committee was charged with revising both the 2013 Center for the Advancement of Pharmacy Education (CAPE) Educational Outcomes (EOs) and the 2016 Entrustable Professional Activities (EPAs). The Committee changed the document name from the CAPE outcomes to COEPA, (Curricular Outcomes and Entrustable Professional Activities) since the EOs and EPAs would now be housed together. A draft of the COEPA EOs and EPAs was released at the AACP July 2022 Annual meeting. After receiving additional stakeholder feedback during and after the meeting, the Committee made additional revisions. The final COEPA document was submitted to and approved by the AACP Board of Directors in November 2022. This COEPA document contains the final version of the 2022 EOs and EPAs. The revised EOs have been reduced to 3 domains and 12 subdomains (from 4 domains and 15 subdomains previously in CAPE 2013) and the revised EPAs have been reduced from 15 to 13 activities.

The AACP Academic Affairs Committee's Guidance for Use of the Curricular Outcomes and Entrustable Professional Activities (COEPA) for Pharmacy Graduates.

The 2021-2023 American Association of Colleges of Pharmacy Academic Affairs Committee (AAC) was charged with and completed the revision of the 2013 Center for the Advancement of Pharmacy Education Outcomes and the 2016 Entrustable Professional Activity (EPA) statements for new pharmacy graduates. This work resulted in a new combined document, the Curricular Outcomes and Entrustable Professional Activities (COEPA) that was unanimously approved by the American Association of Colleges of Pharmacy Board of Directors and was published in the Journal. The AAC was also charged with providing stakeholders with guidance about how to use the new COEPA document. To achieve this charge, the AAC created example objectives for all 12 Educational Outcomes (EOs) and example tasks for all 13 EPAs. Although programs are asked to retain the EO domains, subdomains, one-word descriptors, and descriptions, unless they are adding more EOs or increasing the taxonomy level of a description, colleges and schools of pharmacy can expand or edit the example objectives and example tasks to meet local needs, as these are not designed to be prescriptive. This guidance document is published separately from the COEPA EOs and EPAs to reinforce the message that the example objectives and tasks are modifiable.

Revising the Center for the Advancement of Pharmacy Education (CAPE) Educational Outcomes and Entrustable Professional Activities (EPAs): The Report of the 2021-2022 Academic Affairs Standing Committee.

EXECUTIVE SUMMARY. The 2021-22 Academic Affairs Committee was charged to 1) Update the Center for the Advancement of Pharmacy Education (CAPE) Outcomes and Entrustable Professional Activity (EPA) statements for new pharmacy graduates; 2) Nominate at least one person for an elected AACP or Council Office; and 3) Consider ways that AACP can improve its financial health. This report primarily focuses on the process undertaken by the committee to revise the CAPE Educational Outcomes and EPAs. Proposed changes to the current outcomes are discussed and the reasoning behind these revisions are described. AACP members will have the opportunity to provide feedback prior to the final document being approved and published later this year.

Finalizing the Work Related to the Curriculum Outcomes and Example Objectives and Entrustable Professional Activities (COEPA) Document: The Report of the 2022-2023 Academic Affairs Standing Committee.

The 2022-2023 Academic Affairs Committee (AAC) was charged to (1) complete the Center for the Advancement of Pharmacy Education Outcomes and Entrustable Professional Activities (EPAs) revisions (now renamed as COEPA - Curriculum Outcomes and Entrustable Professional Activities) after receiving feedback at the 2022 American Association of Colleges of Pharmacy (AACP) Annual Meeting; (2) offer guidance on how the revised COEPA education outcomes and EPA statements should be used by member institutions, faculty, preceptor, and students; (3) guide input into the ongoing revision of the Accreditation Council for Pharmacy Education (ACPE) standards for the Doctor of Pharmacy program. The published report of the 2021-2022 AAC outlines the work of the Committee through the spring of 2022.1 This 2022-2023 AAC report focuses on the work related to finalizing the COEPA educational outcomes, EPAs, preamble, and glossary and formally receiving approval from the AACP Board of Directors.2 This report also describes the creation of a COEPA guidance document, including educational outcomes example learning objectives, and EPA example tasks for the Academy, however, the actual guidance document will be published separately. Finally, this current report outlines the feedback the AAC sought, received, synthesized, summarized, and prioritized from key interested and affected parties about the ACPE 2016 standards revisions for the ACPE 2025 draft standards.3 The Committee offers revisions for 1 AACP policy statement pertaining to diversity, equity, inclusion, accessibility, justice, and anti-racism. One new policy statement is also offered that urges ACPE to create accreditation standards for pharmacy education that support diversity, equity, inclusion, accessibility, justice, and anti-racism, despite presence of laws, executive orders, and policies that oppose these concepts.

Young Same-Gender-Loving Men (SGLM) Living with HIV Continue to Experience Symptoms that May Impair Their Retention in Care.

Over half of HIV infections in the U.S. are among young gay, bisexual, and other same-gender-loving men (SGLM). Symptoms affecting these individuals must be clarified in order to be detected and addressed by health care providers. This report describes the symptom prevalence in young SGLM living with HIV. Study participants in an urban context experienced high symptom burden with a median of 6.2 symptoms despite antiretroviral treatment with viral suppression. Most common symptoms included fatigue (57%), depression (54%), insomnia (53%), anxiety (44%), dizziness (33%), and headache (33%). This study showed that young SGLM with HIV experience a high number of symptoms given their age. Health care providers should work to alleviate this symptom burden that affects patients' quality of life and may influence engagement in care.

Development of Entrustable Professional Activities for Specialist Hospice and Palliative Care Pharmacists.

CONTEXT: Entrustable professional activities (EPAs) translate competencies into explicit, practical terms that clearly state the expected roles and responsibilities of clinicians who have achieved proficiency and expertise in a field. EPAs are defined for Hospice and Palliative Medicine physicians but not for other members of Hospice and Palliative Care (HAPC) interprofessional teams, including pharmacists. OBJECTIVES: The objective of this study was to develop EPAs for HAPC pharmacists. METHODS: An 11-member workgroup of HAPC pharmacists was convened to develop candidate EPAs using nominal group and modified-Delphi methods. Content validity index was used as a measure of consensus, defined a priori at ≥ 60%. Vetting occurred via intra- and interprofessional stakeholder reactor groups and a national survey of HAPC pharmacists. RESULTS: Following an iterative process of workgroup and stakeholder consensus-building, 15 HAPC pharmacist EPAs were developed. Among the workgroup, all 15 EPAs reached ≥ 70% consensus, indicating appropriate internal validity. In a national survey of 185 HAPC pharmacists with a 20% response rate, 13 EPAs were rated by most respondents as "essential" and 2 were rated by most respondents as "important but not essential." Respondents indicated the 15 EPA set represented the core professional activities of HAPC pharmacists well (median rating of 5 on a Likert-like scale, IQR 1). CONCLUSION: Fifteen consensus EPAs describe essential activities of HAPC pharmacists in direct patient care, leadership, education, and scholarship. These EPAs will further guide pharmacist training programs, HAPC services seeking to incorporate a specialized pharmacist on the team, and currently practicing HAPC pharmacists.

The Impact of Food on Bioavailability of Oxycodone Myristate: A Case Report.

BACKGROUND: In efforts to reduce misuse of opioids, new abuse deterrent formulations of medications have been developed. Insurers increasingly give abuse-deterrent opioid formulations preferred formulary status, which can result in required formulation rotation for patients. Xtampza® (oxycodone myristate extended-release) is an abuse-deterrent opioid formulation that maintains its extended-release properties with any physical manipulation. Blood levels of oxycodone myristate extended-release (OxyM-ER) may vary with dietary caloric and fat intake. CASE DESCRIPTION: A woman with metastatic breast carcinoma had severe myalgias and arthralgias well-managed with oxycodone hydrochloride extended-release (OxyHCl-ER) and hydrocodone/acetaminophen. A switch from OxyHCl-ER to OxyM-ER resulted in worsened pain management, decreased functional status, and a referral to palliative care (PC). Recognizing calorie-depending pharmacokinetic variability with OxyM-ER, the interdisciplinary PC team obtained a detailed dietary history from the patient, which revealed a low-fat, low-calorie healthy diet with inconsistent meals. After repeated education, the patient changed her diet and had improved pain and functional status without increasing her total daily opioid dose. CONCLUSION: The efficacy of OxyM-ER may be compromised in patients with cancer experiencing anorexia, decreased or inconsistent food intake, or low-fat/low-calorie diets. An interdisciplinary team approach can improve pain control in the setting of "forced" formulary switches to OxyM-ER.

Early Use of the Palliative Approach to Improve Patient Outcomes in HIV Disease: Insights and Findings From the Care and Support Access (CASA) Study 2013-2019.

Young men of color who have sex with men (yMSM) living with human immunodeficiency virus (HIV) in syndemic environments have been difficult-to-retain in care resulting in their being at-risk for poor health outcomes despite availability of effective once-daily antiretroviral treatment (ART). Multiple methods have been implemented to improve outcomes for this cohort; none with sustainable results. Outpatient HIV staff themselves may be a contributing factor. We introduced multidisciplinary staff to the concept of using a palliative approach early (ePA) in outpatient HIV care management to enable them to consider the patient-level complexity of these young men. Young MSM (18-35 years of age) enrolled in and cared for at the intervention site of the Care and Support Access Study (CASA), completed serial surveys over 18 months. Patients' Global and Summary quality of life (QoL) increased during the study at the intervention site (IS) where staff learned about ePA, compared with patients attending the control site (CS) (p=.021 and p=.018, respectively). Using serial surveys of staff members, we found that in the era of HIV disease control, outpatient staff are stressed more by environmental factors than by patients' disease status seen historically in the HIV epidemic. A Community Advisory Panel of HIV stakeholders contributed to all phases of this study and altered language used in educational activities with staff members to describe the patient cohort.

The histone demethylase, Jmjd1a, interacts with the myocardin factors to regulate SMC differentiation marker gene expression.

We and others have previously shown that the myocardin transcription factors play critical roles in the regulation of smooth muscle cell (SMC) differentiation marker gene expression. In a yeast 2-hybrid screen for proteins that interact with myocardin-related transcription factor-A (MRTF-A), we identified the histone 3 lysine 9 (H3K9)-specific demethylase, Jmjd1a. GST pull-down assays demonstrated that Jmjd1a bound all 3 myocardin family members, and further mapping studies showed that the jumonjiC domain of Jmjd1a was sufficient to mediate this interaction. Overexpression of Jmjd1a in multipotential 10T1/2 cells decreased global levels of di-methyl H3K9, stimulated the SM alpha-actin and SM22 promoters, and synergistically enhanced MRTF-A- and myocardin-dependent transactivation. Using chromatin immunoprecipitation assays, we also demonstrated that TGF-beta-mediated upregulation of SMC differentiation marker gene expression in 10T1/2 cells was associated with decreased H3K9 dimethylation at the CArG-containing regions of the SMC differentiation marker gene promoters. Importantly, knockdown of Jmjd1a in 10T1/2 cells and primary rat aortic SMCs by retroviral delivery of siRNA attenuated TGF-beta-induced upregulation of endogenous SM myosin heavy chain expression. These effects were concomitant with increased H3K9 dimethylation at the SMC differentiation marker gene promoters and with inhibition of MRTF-A-dependent transactivation of the SMC-specific transcription. These results suggest, for the first time, that SMC differentiation marker gene expression is regulated by H3K9 methylation and that the effects of the myocardin factors on SMC-specific transcription may involve the recruitment of Jmjd1a to the SMC-specific promoters.

Ten Tips Palliative Care Pharmacists Want the Palliative Care Team to Know When Caring for Patients.

As palliative care (PC) moves upstream in the course of serious illness and the development of drugs and their indications rapidly expand, PC providers must understand common drug indications and adverse effects to ensure safe and effective prescribing. Pharmacists, experts in the nuances of medication management, are valuable resources and colleagues for PC providers. This article will offer PC providers 10 useful clinical pharmacy tips that PC pharmacists think all PC providers should know for safe and effective symptom management. Close collaboration with or addition of a trained pharmacist to your PC team can improve clinical care for all PC patients.

Multicentered Study Evaluating Pharmacy Students' Perception of Palliative Care and Clinical Reasoning Using Script Concordance Testing.

INTRODUCTION: As the role of the pharmacist on the transdisciplinary palliative care team grows, the need for adequate instruction on palliative care and clinical reasoning skills in schools of pharmacy grows accordingly. METHODS: This study evaluates second- and third-year pharmacy students from 6 accredited schools of pharmacy that participated in surveys before and after the delivery of a didactic palliative care elective. The survey collected student demographics, perceptions of the importance of and student skill level in palliative care topics. The script concordance test (SCT) was used to assess clinical decision-making skills on patient cases. Student scores on the SCT were compared to those of a reference panel of experts. RESULTS: A total of 89 students completed the pre-/postsurveys and were included in data analysis. There was no statistically significant difference in student perceived importance of palliative care skills before and after the elective. Students from all 6 institutions showed significant increase in confidence in their palliative care skills at the end of the course. There was also a significant improvement across all institutions in clinical reasoning skills in most of the SCT questions used to assess these skills. CONCLUSIONS: Students choosing an elective in palliative care likely do so because they already have an understanding of the importance of these topics in their future practice settings. Delivery of a palliative care elective in the pharmacy curriculum significantly increases both student confidence in their palliative care skills and their clinical reasoning skills in these areas.

Improved Learning Outcomes After Flipping a Therapeutics Module: Results of a Controlled Trial.

PURPOSE: To evaluate the impact on learning outcomes of flipping a pain management module in a doctor of pharmacy curriculum. METHOD: In a required first-professional-year pharmacology and therapeutics course at the University of Maryland School of Pharmacy, the pain therapeutics content of the pain management module was flipped. This redesign transformed the module from a largely lecture-based, instructor-centered model to a learner-centered model that included a variety of preclass activities and in-class active learning exercises. In spring 2015, the module was taught using the traditional model; in spring 2016, it was taught using the flipped model. The same end-of-module objective structured clinical exam (OSCE) and multiple-choice exam were administered in 2015 to the traditional cohort (TC; n = 156) and in 2016 to the flipped cohort (FC; n = 162). Cohort performance was compared. RESULTS: Learning outcomes improved significantly in the FC: The mean OSCE score improved by 12.33/100 points (P < .0001; 95% CI 10.28-14.38; effect size 1.33), and performance on the multiple-choice exam's therapeutics content improved by 5.07 percentage points (P < .0001; 95% CI 2.56-7.59; effect size 0.45). Student performance on exam items assessing higher cognitive levels significantly improved under the flipped model. Grade distribution on both exams shifted, with significantly more FC students earning an A or B and significantly fewer earning a D or F compared with TC students. CONCLUSIONS: Student performance on knowledge- and skill-based assessments improved significantly after flipping the therapeutics content of a pain management module.

Knowledge, Skills, and Attitudes in Caring for Older Adults With Advanced Illness Among Staff Members of Long-Term Care and Assisted Living Facilities: An Educational Needs Assessment.

In long-term care and assisted living facilities, many groups of health care professionals contribute to the work of the health care team. These staff members perform essential, direct patient care activities. An educational needs assessment was conducted to determine the learning needs and preferences of staff members related to providing care for patients with life-limiting illnesses. Staff members placed importance on understanding topics such as principles of palliative care, pain assessment, pain management, and nonpain symptom management. The majority of survey respondents were also interested in learning more about these topics. The results of this educational needs analysis suggest staff members would benefit from a course tailored to these identified educational needs and designed to overcome previously identified educational barriers.

Smooth muscle cell-specific transcription is regulated by nuclear localization of the myocardin-related transcription factors.

On the basis of our previous studies on RhoA signaling in smooth muscle cells (SMC), we hypothesized that RhoA-mediated nuclear translocalization of the myocardin-related transcription factors (MRTFs) was important for regulating SMC phenotype. MRTF-A protein and MRTF-B message were detected in aortic SMC and in many adult mouse organs that contain a large SMC component. Both MRTFs upregulated SMC-specific promoter activity as well as endogenous SM22alpha expression in multipotential 10T1/2 cells, although to a lesser extent than myocardin. We used enhanced green fluorescent protein (EGFP) fusion proteins to demonstrate that the myocardin factors have dramatically different localization patterns and that the stimulation of SMC-specific transcription by certain RhoA-dependent agonists was likely mediated by increased nuclear translocation of the MRTFs. Importantly, a dominant-negative form of MRTF-A (DeltaB1/B2) that traps endogenous MRTFs in the cytoplasm inhibited the SM alpha-actin, SM22alpha, and SM myosin heavy chain promoters in SMC and attenuated the effects of sphingosine 1-phosphate and transforming growth factor (TGF)-beta on SMC-specific transcription. Our data confirmed the importance of the NH(2)-terminal RPEL domains for regulating MRTF localization, but our analysis of MRTF-A/myocardin chimeras and myocardin RPEL2 mutations indicated that the myocardin B1/B2 region can override this signal. Gel shift assays demonstrated that myocardin factor activity correlated well with ternary complex formation at the SM alpha-actin CArGs and that MRTF-serum response factor interactions were partially dependent on CArG sequence. Taken together, our results indicate that the MRTFs regulate SMC-specific gene expression in at least some SMC subtypes and that regulation of MRTF nuclear localization may be important for the effects of selected agonists on SMC phenotype.

Sphingosine 1-phosphate stimulates smooth muscle cell differentiation and proliferation by activating separate serum response factor co-factors.

Sphingosine 1-phosphate (S1P) is a lipid agonist that regulates smooth muscle cell (SMC) and endothelial cell functions by activating several members of the S1P subfamily of G-protein-coupled Edg receptors. We have shown previously that SMC differentiation is regulated by RhoA-dependent activation of serum response factor (SRF). Because S1P is a strong activator of RhoA, we hypothesized that S1P would stimulate SMC differentiation. Treatment of primary rat aortic SMC cells with S1P activated RhoA as measured by precipitation with a glutathione S-transferase-rhotekin fusion protein. In SMC and 10T1/2 cells, S1P treatment up-regulated the activities of several transiently transfected SMC-specific promoters, and these effects were inhibited by the Rho-kinase inhibitor, Y-27632. S1P also increased smooth muscle alpha-actin protein levels in SMC but had no effect on SRF binding to the smooth muscle alpha-actin CArG B element. Quantitative reverse transcriptase-PCR showed that S1P treatment of SMC or 10T1/2 cells did not increase the mRNA level of either of the recently identified SRF co-factors, myocardin or myocardin-related transcription factor-A (MRTF-A). MRTF-A protein was expressed highly in SMC and 10T1/2 cultures, and importantly the effects of S1P were inhibited by a dominant negative form of MRTF-A indicating that S1P may regulate the transcriptional activity of MRTF-A. Indeed, S1P treatment increased the nuclear localization of FLAG-MRTF-A, and the effect of MRTF-A overexpression on smooth muscle alpha-actin promoter activity was inhibited by dominant negative RhoA. S1P also stimulated SMC growth by activating the early growth response gene, c-fos. This effect was not attenuated by Y-27632 but could be inhibited by the MEK inhibitor, UO126. S1P enhanced SMC growth through ERK-mediated phosphorylation of the SRF co-factor, Elk-1, as measured by gel shift and Elk-1 activation assays. Taken together these results demonstrate that S1P activates multiple signaling pathways in SMC and regulates proliferation by ERK-dependent activation of Elk-1 and differentiation by RhoA-dependent activation of MRTF-A.