Implementation of standard setting for high-stakes objective structured clinical examinations.

BACKGROUND AND PURPOSE: To describe one institution's approach to transformation of high-stakes objective structure clinical examinations (OSCEs) from norm-referenced to criterion-referenced standards setting and to evaluate the impact of these changes on OSCE performance and pass rates. EDUCATIONAL ACTIVITY AND SETTING: The OSCE writing team at the college selected a modified Angoff method appropriate for high-stakes assessments to replace the two standard deviation method previously used. Each member of the OSCE writing team independently reviewed the analytical checklist and calculated a passing score for active stations on OSCEs. Then the group met to determine a final pass score for each station. The team also determined critical cut points for each station, when indicated. After administration of the OSCEs, scores, pass rates, and need for remediation were compared to the previous norm-referenced method. Descriptive statistics were used to summarize the data. FINDINGS: OSCE scores remained relatively unchanged when switched to a criterion-referenced method, but the number of remediators increased up to 2.6 fold. In the first year, the average score increased from 86.8% to 91.7% while the remediation rate increased from 2.8% to 7.4%. In the third year, the average increased from 90.9% to 92% while the remediation rate increased from 6% to 15.6%. Likewise, the fourth-year average increased from 84.9% to 87.5% while the remediation rate increased from 4.4% to 9%. SUMMARY: Transition to a modified Angoff method did not impact average OSCE score but did increase the number of remediations.

Didactic education for the deaf or hard of hearing learner in a pharmacy curriculum: Commentary.

INTRODUCTION: There is a long-standing commitment in higher education to provide parallel experiences for students with disabilities, including those with hearing disabilities or impairments. The commitment remains the same in professional pharmacy school education, with the objective to train competent clinical pharmacy practitioners. COMMENTARY: Limited literature exists to provide schools and colleges of pharmacy (S/COP) with best practices when accommodating students who are deaf or hard of hearing (DHOH) in the didactic pharmacy curriculum. The authors will examine practices implemented at the COP to accommodate students with either a DHOH disability. IMPLICATIONS: Students who are DHOH in didactic pharmacy education require individualized assistance to help ensure success throughout the program. A collaborative approach between the student, disability resources, student affairs office, faculty, and staff help ensure accommodations are met and fosters a culture of inclusiveness.

Brincidofovir: A Novel Agent for the Treatment of Smallpox.

OBJECTIVE: This article reviews the published data encompassing the development, pharmacology, efficacy, and safety of brincidofovir, a nucleotide analogue DNA polymerase inhibitor developed for the treatment of smallpox. DATA SOURCES: A literature review was conducted in PubMed, MEDLINE, and Clinicaltrials.gov from inception up to December 2022, using terms Tembexa, brincidofovir, CMX001, smallpox treatment, and variola treatment. STUDY SELECTION AND DATA EXTRACTION: Data were limited to studies published in English language, which evaluated the efficacy and safety of brincidofovir. DATA SYNTHESIS: Two surrogate animal models were included in the Food and Drug Administration's (FDA) decision to approve brincidofovir: ectromelia virus in mice and rabbitpox in rabbits. Phases 2 and 3 studies established safety for approval. Brincidofovir biweekly for the treatment of disseminated adenovirus disease resulted in all-cause mortality, ranging from 13.8% to 29%. In a study for cytomegalovirus prophylaxis, patients with clinically significant cytomegalovirus infection through week 24 posttransplant was 51.2% with brincidofovir and 52.3% with placebo. CONCLUSIONS: Brincidofovir adds a second oral agent to treat smallpox, with a different mechanism of action than tecovirimat. In the event of a smallpox outbreak, prompt treatment will be necessary to contain its spread. Brincidofovir shows efficacy in surrogate animal models. In healthy volunteers and individuals treated, or used as prophylaxis, for cytomegalovirus or adenovirus, the primary adverse events were gastrointestinal in addition to transient hepatotoxicity. Additionally, excessive deaths were observed in hematopoietic cell transplant patients receiving it as cytomegalovirus prophylaxis, requiring a black box warning.

MenQuadfi (MenACWY-TT): A New Vaccine for Meningococcal Serogroups ACWY.

OBJECTIVE: This article reviews data encompassing the pharmacology, efficacy, and safety of MenACWY-TT (MenQuadfi), a conjugate vaccine to prevent meningococcal disease from serogroups A, C, W, Y. DATA SOURCES: A literature review was conducted in PubMed, MEDLINE, and ClinicalTrials.gov from inception up to July 2021, using the search terms MenQuadfi, meningococcal ACWY vaccine, MCV4, and menacwy. Articles from reference lists were included to identify potential relevant literature. STUDY SELECTION AND DATA EXTRACTION: Data were limited to randomized phase II and III clinical studies published in the English language, evaluating the efficacy and safety of MenACWY-TT. Animal studies and studies not utilizing MenACWY-TT were excluded. DATA SYNTHESIS: One phase II and 4 phase III randomized clinical studies, enrolling approximately 7700 participants, aged 2 years to 97 years old found that MenACWY-TT was noninferior when compared to established MenACWY vaccines, as measured by surrogate immunogenicity end points. In studies evaluating primary dose vaccination, conducted in those aged 2 to 97 years of age, the difference in seroresponse rates, reported by the lower bound of the 95% CI, was (A) 1.1% to 14.8%, (C) 21% to 42.2%, (Y) 7.7% to 24.6%, and (W) 8.9% to 22.5%. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Despite the low incidence of meningococcal disease in the United States, meningococcal disease causes significant morbidity and mortality if not prevented. CONCLUSION: MenACWY-TT is noninferior to currently approved quadrivalent meningococcal vaccines and shows similar immunogenicity and safety as both an initial vaccine for prevention as well as a booster dose.

Impact of supplemental individual verbal defense on confidence, engagement, and performance in a team-based learning therapeutics course.

BACKGROUND AND PURPOSE: Team-based learning (TBL) has been successfully applied to multiple healthcare education disciplines. A primary tenet of TBL is the development of solutions leveraging the collective knowledge of a team rather than the individual competency of any one student. In an effort to enhance individual student accountability, an individual verbal defense (IVD) format was implemented in a multi-campus TBL-based pharmacotherapeutics course. The study sought to investigate the use of TBL-IVD embedded within a traditional TBL format on student engagement, teaching style preferences, and exam performance compared to a TBL-only format. EDUCATIONAL ACTIVITY AND SETTING: In this cross-sectional study, second-year pharmacy students enrolled in a pharmacotherapeutics course during fall 2019 completed an 11-item survey. The survey was designed to assess TBL-IVD on student engagement and teaching style preference. Free-response qualitative feedback was solicited to assess positive-negative themes related to the activity. Aggregate exam performance for community-acquired pneumonia (CAP) related content was compared to historical exam data to assess the impact on student performance. FINDINGS: The majority of students (72%, n = 54) preferred the TBL-IVD compared to a TBL-only format. Students reported higher engagement with TBL-IVD (84%, n = 63). Correct exam responses for CAP related content were higher in the TBL-IVD group (67% vs. 55%, P < .001). Positive themes included an increased opportunity to defend recommendations verbally and increased interaction with an on-campus faculty member. SUMMARY: The study demonstrates the addition of IVD can enhance student perceptions, confidence, and performance within a large, multi-campus, TBL-based pharmacotherapeutics course.

Ciprofloxacin/dexamethasone precipitate formation in the ear canal of a paediatric patient.

This case report describes a paediatric patient diagnosed with otitis externa and treated with topical ciprofloxacin/dexamethasone. The patient completed the course of therapy and then developed precipitate formation from the pharmacological treatment. Laboratory testing of the precipitate confirmed the presence of a large quantity of ciprofloxacin. Removal of the precipitate required the use of an elephant ear washer system and removal with surgical tweezers. This case report investigated a probable topical ciprofloxacin/dexamethasone-induced ear precipitate formation in the ear canal, which, subsequently, was successfully removed from the patient's ear canal.

Intravenous and Oral Posaconazole Pharmacokinetics in a Five-Year-Old With Mucor: A Case Report and Review of the Literature.

Posaconazole is a lipophilic triazole antifungal that exhibits variable absorption when administered orally. It possesses a broad spectrum of activity against various fungi, such as Aspergillus and traditionally resistant molds such as Rhizopus and Mucor, which carry a poor prognosis. Unfortunately, the tablet and suspension formulations of posaconazole are Food and Drug Administration approved for treatment of fungal diseases only in patients older than 13 years of age. Furthermore, the approval of the IV formulation is exclusively for adult patients. Nevertheless, the extended spectrum of activity and available dosage forms make it an attractive option for pediatric use. The data that exist to guide dosing of posaconazole in young pediatric patients are limited primarily to case series and case reports. Thus, we recommend therapeutic drug monitoring to ensure both safety and efficacy in pediatric patients. Herein we describe our experience with both oral and IV posaconazole in the salvage therapy of a 5-year-old female with extensive cutaneous Mucor. In contrast to previous reports, which show larger doses may be necessary to obtain therapeutic concentrations in pediatric patients as compared with adults, our patient reached targeted concentrations with weight-based dosing.

A Simulated Approach to Fostering Competency in End-of-Life Care Among Pharmacy Students.

Objective. To determine if pharmacy students participating in simulation-based scenarios reported fewer learning needs about the transition from acute to end-of-life (EOL) care compared to students participating in solely case-based scenario delivery. Methods. Four end-of-life cases were developed for both paper-based case study and simulation delivery. Pharmacy students on three distant campuses were exposed to the case study approach while four teams of nine to ten pharmacy students were exposed to simulated versions of the same cases. A validated questionnaire was administered before and after exposure to assess end-of-life care learning needs. Results were analyzed following a Bonferroni-adjustment for multiple testing. Results. The case study groups produced similar pre/post changes on the questionnaire. After results were pooled and compared to the simulation only group, significantly higher changes in pre/post scores were found for the simulation group. Conclusion. Pharmacy students exposed to simulated EOL scenarios experienced significantly reduced learning needs following the scenarios, unlike their classroom-based counterparts.

Integrase Inhibitors: After 10 Years of Experience, Is the Best Yet to Come?

The era of the integrase strand transfer inhibitors (INSTIs) for the treatment of human immunodeficiency virus (HIV) infection began with raltegravir in 2007. Since that time, several other INSTIs have been introduced including elvitegravir, dolutegravir, and, most recently, bictegravir, that have shown great utility as part of antiretroviral regimens in both treatment-naive and treatment-experienced patients. At present, antiretroviral guidelines fully endorse the INSTI class as part of all first-line treatment regimens. After 10 years of experience with INSTIs, newer agents are on the horizon such as cabotegravir and MK-2048 for potential use as either HIV pre-exposure prophylaxis or maintenance therapy. This review provides a brief overview of the INSTI class including agents currently available and those still in development, reviews available data from both completed and ongoing clinical trials, and outlines simplification strategies using INSTIs.

Using interprofessional medication management simulations to impact student attitudes toward teamwork to prevent medication errors.

BACKGROUND: We developed and implemented a project incorporating ACPE Standard 11 and all Core IPEC competencies at a public University located at a medical center. The project was a collaboration between the colleges of nursing, pharmacy, and medicine at a distance campus location. INTERPROFESSIONAL EDUCATION ACTIVITY: Our Interprofessional Education Activity, which targeted all three elements of ACPE Standard 11, provided TeamSTEPPS® training followed by four medical error simulations. A debriefing took place after each scenario within a team as well as with all four groups following each simulation session. The Teamwork Attitudes Questionnaire (TTAQ) was used to evaluate the activity. DISCUSSION: Findings from our interprofessional education activity indicate that while students entered the activity already perceiving teamwork as a positive aspect of safe care delivery, significant improvement in attitudes post training toward specific team constructs was seen across all five domains. The project helped inform the structure of a replication of this effort that is currently underway, with a focus on embedding it in the curricula of all three programs (medicine, pharmacy, and nursing) across campuses. IMPLICATIONS: In summary, working collaboratively in a team while being exposed to a series of medication management scenarios enhances teamwork attitudes as well as potentially improving performance. Based on the positive initial results, plans have begun to extend the experience to other campuses and include a wider group of students.

Tenofovir Alafenamide for the Treatment of Chronic Hepatitis B Monoinfection.

Tenofovir alafenamide (TAF) is indicated for adult patients with chronic hepatitis B virus (HBV) infection with compensated liver disease at an oral dose of 25 mg/day. TAF is a more stable prodrug in the plasma than tenofovir disoproxil fumarate (TDF), leading to decreased plasma exposure of tenofovir. Decreased exposure is thought to reduce the risk of long-term TDF toxicities, such as nephrotoxicity and decreased bone mineral density (BMD). TAF, a nucleotide reverse transcriptase inhibitor, has the same mechanism of action as TDF. The results of phase III primary trials and extensions showed that TAF is noninferior to TDF at suppressing the HBV viral load in treatment-naive and treatment-experienced HBeAg-negative and HBeAg-positive patients at 48 weeks, 96 weeks, and 144 weeks of therapy. The most commonly reported adverse events were headache, abdominal pain, fatigue, cough, nausea, and back pain. At all evaluated time points (out to 144 wks of treatment), patients who received TAF had less risk of nephrotoxicity and less of a decline in BMD than the patients who received TDF. TAF appears to be safe in patients with a creatinine clearance (Clcr ) above 15 ml/min; however, TAF is not currently recommended in patients with an estimated Clcr below this threshold. TAF is safe in patients with mild hepatic impairment but is not currently recommended in patients with moderate or severe hepatic impairment (Child-Pugh class B or C).

The pharmacological challenges of treating tuberculosis and HIV coinfections.

INTRODUCTION: Tuberculosis (TB) is the most prevalent opportunistic infection among HIV patients, and the leading cause of death among HIV patients worldwide. Simultaneous treatment of both diseases is recommended by current guidelines, but can be challenging due to the potential for drug-drug interactions, overlapping toxicities, difficulty adhering to medications, and an increased risk for immune reconstitution inflammatory syndrome (IRIS). Clinical manifestations of TB can also vary between HIV-infected patients and uninfected patients, which can increase the risk for delayed diagnosis. Areas covered: Topics covered in this review include the following: the inter-related pathophysiology of HIV and TB; clinical manifestations and diagnosis; drug-drug interactions, particularly the rifamycins with the antiretrovirals; IRIS presentation and treatment, as well as a discussion on overlapping toxicity between the two disease states. Expert commentary: The complexity of managing these two disease states simultaneously requires a multidisciplinary approach to care and dedicated resources. If properly funded, TB/HIV co-infection will continue to decline over the coming years.

ISONIAZID AND RIFAMPIN PHARMACOKINETICS IN TWO ASIAN ELEPHANTS (ELEPHAS MAXIMUS) INFECTED WITH MYCOBACTERIUM TUBERCULOSIS.

This report describes the pharmacokinetic profiles of chronically administered oral isoniazid and rifampin in one adult male and one adult female Asian elephant ( Elephas maximus ) that were asymptomatically infected with Mycobacterium tuberculosis . Rifampin's half-life was reduced when compared to previous single-dose pharmacokinetic profiles of healthy uninfected Asian elephants. Both elephants experienced delayed absorption of isoniazid and rifampin as compared to previous pharmacokinetic studies in this species. The altered pharmacokinetics of both drugs in repeated-dosing clinical situations underscores the need for individual therapeutic drug monitoring for tuberculosis treatment.

A HAART-Breaking Review of Alternative Antiretroviral Administration: Practical Considerations with Crushing and Enteral Tube Scenarios.

Selection of an appropriate antiretroviral regimen for the patient infected with human immunodeficiency virus can be challenging, as various considerations must be taken into account including viral resistance mutations, patient comorbidities, drug interactions, and the potential for drug-related adverse effects and toxicities. Treatment is further complicated when a clinical scenario arises requiring an alteration in the dosage form. Factors ranging from dysphagia to administration through an enteral feeding tube can affect decisions regarding antiretroviral dosage forms. Limited pharmacokinetic data exist regarding the alteration of antiretroviral medications from their original form. Bioavailability may vary substantially between dosage forms, which can lead to unpredictable drug concentrations. Supratherapeutic or subtherapeutic antiretroviral drug concentrations can result in increased toxicity, virologic failure, or the emergence of drug resistance. We performed a systematic literature search to review the available antiretroviral literature on the modification of solid dosage forms as well as alternative routes of administration of oral antiretroviral agents and their application to clinical practice.

Rifapentine for the treatment of latent tuberculosis.

INTRODUCTION: The goal of this article is to review the use of rifapentine in the treatment of latent tuberculosis infection (LTBI). Controlling LTBI is an important part of the global strategy to end the spread of tuberculosis. Rifapentine's potent sterilizing effect against Mycobacterium tuberculosis combined with its long half-life make it an attractive LTBI treatment option. Areas covered: A systematic literature search of Pubmed using the terms 'rifapentine' and 'tuberculosis' was performed. Articles identified were cross-referenced for other relevant publications. The mechanisms of action and resistance, pharmacokinetic and pharmacodynamics, potential drug interactions and side effects are discussed. Expert commentary: Rifapentine in combination with isoniazid for twelve weeks is the best available option for treating latent TB in the majority of patients in the United States due to its favorable safety profile and the increased likelihood of completing therapy. Currently, rifapentine is not registered or available in other countries.

Voriconazole monitoring in children with invasive fungal infections.

OBJECTIVES: The primary objective of this study was to determine the optimal daily dose of voriconazole required to achieve therapeutic trough concentrations in children 1 month to 18 years of age. The secondary objective was to analyze the association between voriconazole trough concentrations and clinical and microbiological outcomes, toxicity, and mortality. METHODS: This study was a retrospective chart review (October 2009 to August 2012) of pediatric oncology/bone marrow transplant patients with proven or probable invasive fungal infections treated with intravenous or oral voriconazole. Patients were excluded if they were older than 18 years of age, had no voriconazole concentrations drawn during the study period, or received voriconazole prior to the study period. RESULTS: Thirty-four patients were reviewed; 11 patients met all criteria for inclusion. There were 6 males and 5 females, with a median age of 8 years (range: 0.8-14.8) and a median weight of 27 kg (range: 9-74). Doses were adjusted to a median 6 mg/kg/dose (range: 3-8.7 mg/kg/dose) given every 8 (n = 5) to 12 (n = 6) hours; dose regimens varied greatly. All but 1 child achieved a voriconazole trough concentration above 1 mg/L; 7 children had a trough concentration above 2 mg/L. The median time to achieve a therapeutic trough concentration was 11 days (range: 6-37 days). Therapy failed for 4 of 11 patients, including 3 of the 4 youngest patients (p=0.022). Three of the 4 for whom therapy failed also had voriconazole trough concentrations less than 2 mg/L; this did not reach statistical significance. Voriconazole therapy was discontinued in 2 patients due to toxicity. CONCLUSIONS: This study confirmed that voriconazole pharmacokinetics vary greatly in pediatric oncology/bone marrow transplant patients. "Optimal" doses varied over nearly a 3-fold range. Younger patients may be at greater risk of poor outcomes and may require additional monitoring and dose adjustment.

Medications and monitoring in nontuberculous mycobacteria infections.

The treatment of infections caused by nontuberculous mycobacteria (NTM) is challenging because multidrug regimens with limited efficacy and considerable toxicity are required. Current treatment of NTM is largely empiric. None of the NTM drugs were specifically developed for the treatment of NTM; the rationale for their use was often extrapolated from the treatment of tuberculosis. This article reviews key features of the drugs that are most commonly used for NTM infections, and provides monitoring parameters. With this information, clinicians can make the most of the limited options available. Considerable research is needed to optimize the treatment of NTM.

Protein binding of rifapentine and its 25-desacetyl metabolite in patients with pulmonary tuberculosis.

Rifapentine is highly protein bound in blood, but the free, unbound drug is the microbiologically active fraction. In this exploratory study, we characterized the free plasma fraction of rifapentine in 41 patients with tuberculosis. We found a lower total rifapentine concentration but significantly higher free rifapentine levels in African patients of black race compared to non-Africans. These data support larger pharmacokinetic/pharmacodynamic studies to confirm these findings and assess free rifapentine in relation to microbiological and clinical outcomes.