Medical Cannabis Received by Patients According to Qualifying Condition in a US State Cannabis Program: Product Choice, Dosing, and Age-Related Trends.

Background: Little is known about the distribution of cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) to patients participating in state medical cannabis programs. The Minnesota cannabis program requires third-party testing of products with limited formulations of cannabis for distribution to patients. Objective: To characterize the distribution of cannabis products, their CBD/THC content, and dosing among patients with qualifying conditions. Methods: This is a retrospective analysis of ∼50% of registered users receiving medical cannabis in Minnesota (June 16, 2016, to November 15, 2019). Data included formulation, CBD/THC prescribed doses, and qualifying conditions. The primary end points were calculated using daily dose and duration of use. Comparisons were made for CBD and THC total daily dose dispensed, patient age, and approved product. Nonparametric statistical tests were used (significance was set at p < 0.05). Results: A total of 11,520 patients were listed with 1 qualifying condition. The most common condition was intractable pain (60.0%). Median dispensation duration varied from 53 days (cancer) to 322 days (muscle spasms). Most (≥62.8%) patients across all qualifying conditions received both CBD and THC. Median THC dose was lower in older (≥65 years) compared with younger adults with intractable pain (p < 0.0001) and cancer patients (p = 0.0152), and the same pattern was found CBD dose with seizure (p = 0.0498) patients. For commercial products with Food and Drug Administration indications, the median CBD total daily dose was 86.9% lower than the recommended doses for patients with seizures (Epidiolex: Jazz Pharmaceuticals, Palo Alto CA) and median THC total daily dose was 65.3% (Syndros: Benuvia Manufacturing, Round Rock, TX) or 79.3% lower (Marinol: Banner Pharmacaps, Inc., High Point, NC) for cancer patients. Conclusions: A majority of patients received products containing both CBD and THC. Dosages varied by age group and were lower than recommended for conditions with Food and Drug Administration-approved products. Complex pharmacokinetics of THC and CBD, possible age-related changes in physiology, unknown efficacy, and potential for drug interactions all increase the need for monitoring of patients receiving cannabis products. (Curr Ther Res Clin Exp. 2023; 84:XXX-XXX).

Assessing pharmacy students' baseline tolerance for ambiguity, burnout, empathy, quality of life, and stress.

INTRODUCTION: Several factors may affect student wellbeing, including tolerance for ambiguity, burnout, empathy, quality of life, and stress. A better understanding of how pharmacy students score on these scales relative to other health professional students could help educators and schools address and improve student wellbeing. The study objective was to determine a baseline measure of pharmacy student tolerance for ambiguity, burnout, empathy, quality of life, and stress. METHODS: A voluntary survey including several assessment scales (Tolerance for Ambiguity, Oldenburg Burnout Inventory, Interpersonal Reactivity Index [empathy], Quality of Life Scale, and Perceived Stress Scale) was sent by email to all pharmacy students within a standalone college of pharmacy. RESULTS: Two hundred thirty-one pharmacy students completed all aspects of the survey. Comparing each scale with sex, female students trended higher in Interpersonal Reactivity Index and scored significantly higher on the Oldenburg Burnout Inventory (disengagement), while male students scored significantly higher for Quality of Life. Fourth-year students scored significantly higher on the Tolerance for Ambiguity scale as compared to first- and second-year students and on the Quality of Life scale as compared with third-year students. Third-year students experienced the greatest levels of burnout. Differences were also noted based on students' anticipated area of practice (empathy) and desire to work with an underserved population (empathy and stress). CONCLUSIONS: Pharmacy students' responses to the included scales varied greatly when considering various demographic parameters. The significant differences identified are illuminating and represent potential areas for curricular improvement, student support, and further study within pharmacy school curricula.

Inclusion of the Pharmacist Patient Care Process in Doctor of Pharmacy Curricula.

Objective. With the inclusion of the Pharmacists' Patient Care Process (PPCP) in the most recent Accreditation Council for Pharmacy Education standards, institutions must determine how best to vertically and horizontally integrate and assess the PPCP in the curriculum. The objective of this study was to identify the breadth and depth of PPCP implementation as well as faculty involvement in teaching the PPCP at ACPE-accredited institutions.Methods. A survey to address the study objectives was developed, piloted, and distributed electronically to all US pharmacy institutions in candidate or accredited status. Electronic reminders were implemented to improve response rates. The data were analyzed descriptively.Results. Approximately 70% of institutions responded to the survey. Integration of the PPCP was most often championed by an individual faculty member and/or a committee. Practice faculty taught PPCP at nearly all institutions, while only a third of survey respondents reported that foundational and social administrative faculty taught the PPCP. Development related to PPCP curricular integration mainly focused on preceptors. Most institutions integrated the PPCP through the didactic and experiential curriculum in an approach that allowed for reinforcement or mastery of concepts. There were limited integration efforts into interprofessional education. Institutions had a plan for assessing the effectiveness of the integration, but were varied in their approach.Conclusion. Institutions have embraced integrating the PPCP into their curricula, didactically and experientially. Progress still needs to be made regarding inclusion of all faculty in teaching the PPCP as well as integrating the PPCP into other key curricular areas, such as interprofessional learning. Faculty development efforts may be beneficial to address these aspects.

Moving out of disciplinary silos - Integration of the Pharmacists' Patient Care Process.

INTRODUCTION: In order to better delineate the specific roles of the pharmacist in generating positive health outcomes, pharmacy programs have incorporated the Pharmacists' Patient Care Process (PPCP). However, there has been limited integration in disciplines outside of pharmacy practice. PERSPECTIVE: This article makes the case that schools need to commit to fully integrating the PPCP that is inclusive of all disciplines. By fostering such integration, all faculty can recognize their role in creating practice-ready, team-ready pharmacists that are consistent, collaborative, and drive positive patient health outcomes. There also is likely innovative integrative efforts being done related to the PPCP in non-practice disciplines, and this article provides some ideas for future scholarly efforts. IMPLICATIONS: If the academy embraces the PPCP fully, we can unite and demonstrate how pharmacists contribute value to the healthcare team.

Multitargeting the sleep-pain interaction with pharmacological approaches: A narrative review with suggestions on new avenues of investigation.

The multimorbidity formed by sleep disturbances and pain conditions is highly prevalent and has a significant impact in global health and in the socioeconomic system. Although different approaches have been directed toward its management, evidence regarding an optimal treatment is lacking, and pharmacological options are often preferred. Health professionals (e.g., pain and sleep clinicians) tend to focus on their respective expertise, targeting a single symptom with a single drug. This may increase polypharmacy and the risk of drug interactions, adverse events, and mortality. Hence, the use of medications that can directly or indirectly improve sleep, pain, and other possible accompanying conditions without exacerbating them becomes especially relevant. The objectives of this comprehensive review are to: a) describe the beneficial or deleterious effects that some commonly used medications to manage pain have on sleep and sleep disorders; and b) describe the beneficial or deleterious effects that frequently prescribed medications for sleep may have on pain. Moreover, medications targeting some specific sleep-pain interactions will be suggested and future directions for improving sleep and alleviating pain of these patients will be provided with clinical and research perspectives.

Pharmacy Education Needs to Address Diagnostic Safety.

The American Association of Colleges of Pharmacy, the Accreditation Council for Pharmacy Education, and the Center for the Advancement of Pharmacy Education frame patient safety from the perspective of medication management, which is also the current focus of pharmacy education and training. With the growing appreciation that diagnostic errors represent an urgent and actionable patient safety concern, the National Academy of Medicine has recommended diagnostic safety training for all health care professions. The Society to Improve Diagnosis in Medicine has worked with an interprofessional consensus group to identify a set of 12 key competencies necessary to achieve diagnostic quality and safety that focuses on individual, team-based, and system-related competencies. Much of this already exists in pharmacy education, but pharmacy training programs need to give graduates more guidance on how they contribute to the diagnostic process and the prevention and detection of diagnostic errors. We describe the current state of progress in this regard, and what steps are needed by training programs to provide content and assessment so that graduates achieve the requisite competencies. Governing and advisory bodies need to expand the expectations around patient safety to include diagnostic safety.

Iron supplements in nursing home patients associated with reduced carbamazepine absorption.

Persons in nursing homes receive a number of medications that may interfere with the pharmacokinetics of carbamazepine (CBZ). The aim of our study was to determine factors that may affect the pharmacokinetics of CBZ in elderly nursing home patients. METHODS: CBZ concentration data collected from 60 nursing homes across the US were evaluated. Inclusion criteria included residency in a nursing home for at least 2 months, age 65 years or older, a stable dosing regimen of CBZ for at least 4 weeks (considered steady state), available CBZ concentration, and complete information regarding all co-medications. Using a nonlinear mixed-effects model, the data were adequately described by a one-compartment model with first-order absorption and elimination. Goodness-of-fit plots, plausibility of parameter estimates, visual predictive check and nonparametric bootstrap were used to evaluate the models. MAIN FINDINGS: The final data set consisted of 345 CBZ concentrations from 99 subjects (38 males, 61 females). The population estimate of apparent clearance (CL/F) for a 70-kg person was 3.69 L/hr (RSE 6.9%). Residents were receiving either immediate (93.9%) or extended release (6.1%) formulation of CBZ and the Ka of each formulation was fixed to literature values. Age, sex, and co-medications had no effect on CL/F and apparent volume of distribution. Iron supplementation, which was taken by 16% of the residents, resulted in a 33% decrease in bioavailability (p < 0.001). No other medications were found to have an effect. CONCLUSIONS: Results from this pharmacokinetic study indicate that use of iron supplementation is associated with a reduction in absorption of CBZ and may need to be considered when dosing CBZ in patients taking iron supplementation.

AACP Special Taskforce White Paper on Diversifying Our Investment in Human Capital.

The 2015-2017 American Association of Colleges of Pharmacy (AACP) Special Taskforce on Diversifying our Investment in Human Capital was appointed for a two-year term, due to the rigors and complexities of its charges. This report serves as a white paper for academic pharmacy on diversifying our investment in human capital. The Taskforce developed and recommended a representation statement that was adapted and adopted by the AACP House of Delegates at the 2016 AACP Annual Meeting. In addition, the Taskforce developed a diversity statement for the Association that was adopted by the AACP Board of Directors in 2017. The Taskforce also provides recommendations to AACP and to academic pharmacy in this white paper.

Factors in Variability of Serial Gabapentin Concentrations in Elderly Patients with Epilepsy.

OBJECTIVES: To characterize and quantify the variability of serial gabapentin concentrations in elderly patients with epilepsy. METHODS: This study included 83 patients (age ≥ 60 yrs) from an 18-center randomized double-blind double-dummy parallel study from the Veterans Affairs Cooperative 428 Study. All patients were taking 1500 mg/day gabapentin. Within-person coefficient of variation (CV) in gabapentin concentrations, measured weekly to bimonthly for up to 52 weeks, then quarterly, was computed. Impact of patient characteristics on gabapentin concentrations (linear mixed model) and CV (linear regression) were estimated. RESULTS: A total of 482 gabapentin concentration measurements were available for analysis. Gabapentin concentrations and intrapatient CVs ranged from 0.5 to 22.6 µg/ml (mean 7.9 µg/ml, standard deviation [SD] 4.1 µg/ml) and 2% to 79% (mean 27.9%, SD 15.3%), respectively, across all visits. Intrapatient CV was higher by 7.3% for those with a body mass index of ≥ 30 kg/m2 (coefficient = 7.3, p=0.04). CVs were on average 0.5% higher for each 1-unit higher CV in creatinine clearance (coefficient = 0.5, p=0.03) and 1.2% higher for each 1-hour longer mean time after dose (coefficient = 1.2, p=0.04). CONCLUSIONS: Substantial intrapatient variability in serial gabapentin concentration was noted in elderly patients with epilepsy. Creatinine clearance, time of sampling relative to dose, and obesity were found to be positively associated with variability.

Pharmacokinetics and Saturable Absorption of Gabapentin in Nursing Home Elderly Patients.

Pharmacokinetic data of gabapentin (GBP) in community-dwelling elderly patients show a significant effect of advanced age on GBP pharmacokinetics due to altered renal function. However, there are no data in elderly nursing home (NH) patients to evaluate gabapentin absorption and elimination. Our objective was to characterize the pharmacokinetics of GBP in elderly nursing home patients maintained on GBP therapy. This was a prospective pharmacokinetic study in elderly nursing home patients (≥60 years) receiving GBP for the management of chronic pain or epilepsy from seven nursing homes. Pharmacokinetic parameters were estimated by nonlinear mixed-effects modeling. A one-compartment model described the data and clearance (CL) was associated with estimated glomerular filtration rate (eGFR) (p < 0.0001). The GBP CL in elderly nursing home patients was 2.93 L/h. After adjusting for the effect of GFR, GBP CL was not affected by age, sex, body weight, or comorbidity scores. No significant effects of body size measures, age, and sex were detected on volume of distribution. Dose-dependent bioavailability of GBP was demonstrated, and the saturable absorption profile was described by a nonlinear hyperbolic function. Prediction-corrected visual predictive check (pc-VPC) suggests adequate fixed- and random-effects models that successfully simulated the mean trend and variability in gabapentin concentration-time profiles. In this analysis, the parameters of the hyperbolic nonlinearity appear to be similar between elderly and younger adults.

Strategies and steps fostering the success of medication management services in community pharmacies.

OBJECTIVES: To identify and describe the steps and strategies that community pharmacies with established medication management services have used to integrate medication management services into their practice settings. DESIGN: Qualitative case study with semistructured interviews and focus groups. SETTING: Community pharmacy organizations in Minnesota. PARTICIPANTS: Pharmacists and pharmacy leadership from 4 different pharmacy organizations including independent, chain, and health system pharmacies. INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: Qualitative case study analysis of community pharmacy management and pharmacists' perceptions of the factors that led to the establishment and sustainability of their medication management programs. RESULTS: Focus groups and interviews were undertaken with 25 pharmacists and pharmacy leaders from 4 distinct community pharmacy organizations from April to June 2015. Five themes emerged, representing specific implementation and continuation stages of medication management services in community practice: Deciding to Act, Setting the Stage, Executing the Service, Sticking to It, and Continuing to Grow. CONCLUSION: This study sheds light on key stages that have commonly occurred across community pharmacies that are delivering medication management services. The results of this work may serve as a road map for other community pharmacies looking to integrate medication management services into their own practice settings.

A flowchart for selecting an ointment base.

UNLABELLED: OBJECTIVES. To improve students' skills in selecting appropriate ointment bases through the development and implementation of a flowchart. DESIGN: A flowchart was designed to help students select the appropriate base for an ointment. Students used the flowchart throughout the semester in both dry and wet laboratory activities. At the end of the semester, students completed a dry laboratory practical that required them to select an appropriate ointment base and levigating agent. ASSESSMENT: Student performance data from the year prior to implementation was compared to data for 2 years after implementation. Calculation, procedure, and labeling errors also were compared. Prior to implementation of the flowchart, 51 of 101 students selected the correct base. After implementation, 169 of 212 students selected the correct base (p<0.001). Calculation, procedure, and labeling errors were not significantly different. CONCLUSION. Use of a flowchart to select an ointment base improved student performance when used in the context of a dry laboratory assignment.

Safety of an intravenous formulation of lamotrigine.

PURPOSE: Intravenous (IV) formulations are useful when treating patients where oral administration is not possible and to study certain pharmacokinetic parameters such as bioavailability. We developed a stable-labeled IV formulation of lamotrigine (LTG) for studying pharmacokinetics in epilepsy patients. METHODS: Stable-labeled IV LTG was given to 20 persons with epilepsy (6 men; 14 women) with a mean age of 34.8 years (SD 11.7). A 50mg dose of LTG (stable labeled) was given intravenously and replaced 50mg of the regular morning oral dose of LTG (unlabeled, commercially available formulation). RESULTS: No significant changes in blood pressure, heart rate, or adverse events including rash were attributed to administration of a 50-mg dose of the intravenous LTG formulation. CONCLUSION: Our results show that LTG base that is complexed with 2-hydroxypropyl-ß-cyclodextrin and stable-labeled can be given safely as a tracer replacement dose.

A pharmacotherapy capstone course to advance pharmacy students' clinical documentation skills.

OBJECTIVE: To implement and assess the effectiveness of a capstone pharmacotherapy course designed to integrate in-class curriculum using patient cases and drug-information questions. The course was intended to improve third-year doctor of pharmacy (PharmD) students' clinical documentation skills in preparation for beginning advanced pharmacy practice experiences (APPEs). DESIGN: This 2-credit, semester-long course consisted of 6 patient cases and 12 drug-information questions posted electronically on an Internet-based medical chart, a public health presentation, a knowledge examination, and an objective standardized performance assessment. In class, students engaged in active-learning exercises and clinical problem-solving. Students worked outside of class in small groups to retrieve and discuss assigned articles and review medication information in preparation for in-class discussions. ASSESSMENT: A rubric was used to assess the patient cases and questions that students completed and submitted individually. Data for 4 consecutive course offerings (n=622) were then analyzed. A significant improvement was found in the "misplaced" but not the "missing" documentation ratings for both assessment and plan notes in the final assessment compared with baseline. In course evaluations, the majority of students agreed that the course integrated material across the curriculum (97%) and improved their clinical writing skills (80.5%). CONCLUSION: A capstone pharmacy course was successful in integrating and reviewing much of the material covered across the PharmD curriculum and in improving students' clinical documentation skills.

Variability of carbamazepine and valproate concentrations in elderly nursing home residents.

PURPOSE: Measuring antiepileptic drug (AED) concentrations is common practice in nursing homes. Phenytoin (PHT) concentrations fluctuate substantially in many nursing home residents under constant dose conditions; however, the stability of other AED concentrations has not been studied. We investigated the variability of carbamazepine (CBZ) and valproate (VPA) concentrations under constant dose conditions in US nursing home residents. METHODS: A database of elderly persons (≥65 years) in 119 nursing homes throughout the US was reviewed for residents with at least one measurement of total PHT, CBZ or VPA. Inclusion criteria for this study were three or more serum concentration measurements while on the same dose of CBZ or VPA, a two-month minimum stay, and no interfering co-medications (inducers or inhibitors). Enrollment occurred over a 2-year period. Data were collected on residents for a minimum of 6 months. KEY FINDINGS: Of the 593 residents identified, 245 had CBZ or VPA concentrations measured and 44 (18%) met inclusion criteria (22 on CBZ and 22 VPA). Some subjects had little variability in AED concentrations, others had large fluctuations. Total CBZ concentrations within individuals varied as little as 0mg/L to as much as 6.3mg/L and total VPA concentrations as little as 10.0mg/L to as much as 77.6mg/L. SIGNIFICANCE: The variability of PHT, CBZ, and VPA concentrations in many but not all nursing home residents implies that a re-evaluation of the role of AED concentration measurements in the management of patients is needed. Strategies for use and interpretation of AED concentration measurements need to be reevaluated.

A sensitive capillary GC-MS method for analysis of topiramate from plasma obtained from single-dose studies.

Topiramate (Topamax®) is an antiepileptic medication used as adjunctive and monotherapy in patients with epilepsy and for migraine prophylaxis. A GC-MS assay was developed that was capable of detecting topiramate plasma concentrations following a single rectal or oral dose administration. Topiramate plasma samples were prepared by solid-phase extraction and were quantified by GC-MS analysis. The topiramate standard curves were split from 0.1 to 4 µg/mL and from 4 to 40 µg/mL in order to give a more accurate determination of the topiramate concentration. The accuracy of the standards ranged from 94.6 to 107.3% and the precision (%CV) ranged from 1.0 to 5.3% for both curves at all concentrations. The %CV for quality controls was <7.6%. The assay is both accurate and precise and will be used to complete future pharmacokinetic studies.

Safety of an IV formulation of carbamazepine.

An intravenous formulation of carbamazepine (CBZ) was administered to 113 (60 male; 53 female) persons with epilepsy aged 19-87 years. Subjects received 100mg of study drug as replacement for 100mg of their usual morning dose of CBZ. There were no significant changes in blood pressure or heart rate suggesting that this formulation can be developed as replacement therapy for persons unable to take oral CBZ.

Population pharmacokinetics of valproic acid concentrations in elderly nursing home residents.

The objective of this study was to identify factors that affect valproic acid (VPA) apparent clearance (CL/F) in elderly nursing home residents. Inclusion criteria included residency in a nursing home for at least 2 months, aged 65 years or older, a stable dosing regimen of VPA for at least 4 weeks, VPA concentration, and complete dosing information. CL/F was analyzed by a nonlinear mixed effects model. A one-compartment model with first-order absorption and elimination was used. Both volume and absorption rate constant were fixed (14 L and 1 hr, respectively). Covariates were tested by forward inclusion and backward elimination. Interindividual variability in clearance was estimated using an exponential error model and expressed as a coefficient of variation. Residual error was estimated using a combined additive and constant coefficient of variation error model. The study consisted of 405 observations from 146 (52 men, 94 women) elderly nursing home residents. CL/F was not affected by age or weight. The population CL/F was 0.843 L/hr. CL/F was 1) 27% lower in female residents; 2) 41% greater when the resident was on concomitant metabolic inducers carbamazepine or phenytoin cotherapy; and 3) 25% greater when the syrup formulation was used. Variability in CL/F was 32.9%. Coefficient of variation and standard deviation of the residual error were 18.2% and 10.6 mg/L, respectively. The increased CL/F in patients taking VPA syrup may be the result of a decreased bioavailability (F) rather than an increased CL that could be associated with pathology requiring use of the syrup rather than an inherent property of the drug formulation. The results from this study may be useful for individualizing dose regimens in the nursing home population based on patient-specific factors.

Carbamazepine dose-concentration relationship in elderly nursing home residents.

PURPOSE: To describe the dose-concentration relationships of carbamazepine (CBZ) in elderly nursing home residents and the effect of sex, age, and type of co-medications. RESULTS: This is a cross-sectional study of elderly (> or = 65 years) nursing home residents across the United States (N=92). Data collection was from 1 June 1998 to 31 December 2000. The mean CBZ dose was 9.2+/-5.4 mg/(kg day(-1)) (+/-Standard Deviation) and serum concentration was 5.9+/-2.2mg/L. The daily dose was significantly lower in the oldest-old age group (> or = 85 years, mean 476.9 mg/day (95% confidence interval CI) 326.5-627.3) as compared to the dose in the young-old (65-74 years, mean 724.4 mg/day (CI) 603.4-845.4) (p=0.016). Adjusted for body weight, doses were similar on a mg/(kg day(-1)) basis. The majority of observed CBZ serum concentrations were at the lower end (67.4%) or below (20.7%) the suggested therapeutic range for younger adult outpatients. CONCLUSIONS: Total daily CBZ doses and patient weight decreased with age. The average dose for elderly nursing home residents was approximately 9 mg/(kg day(-1)). Carbamazepine serum concentrations were lower than those used for younger adults, suggesting that these patients may be more sensitive to CBZ.