Successful Treatment of Balamuthia mandrillaris Granulomatous Amebic Encephalitis with Nitroxoline.

A patient in California, USA, with rare and usually fatal Balamuthia mandrillaris granulomatous amebic encephalitis survived after receiving treatment with a regimen that included the repurposed drug nitroxoline. Nitroxoline, which is a quinolone typically used to treat urinary tract infections, was identified in a screen for drugs with amebicidal activity against Balamuthia.

Challenges and advances in the medical treatment of granulomatous amebic encephalitis.

Granulomatous amebic encephalitis, caused by the free-living amebae Balamuthia mandrillaris or Acanthamoeba species, is a rare and deadly infectious syndrome with a current mortality rate of >90%. Much work remains to define the optimal treatment for these infections. Here, we provide a comprehensive overview of the supporting evidence behind antimicrobials currently recommended by the Centers for Disease Control and Prevention (CDC) with updated statistics on survival rates and medication usage from the CDC Free-Living Ameba Database. We also discuss promising treatments, especially the emerging therapeutic agent nitroxoline, and provide recommendations for the next steps in this area.

Changes in Pharmacy Students' Self-Reported Learning Strategies Across a Four-Year Doctor of Pharmacy Program.

Objective. Few studies describe changes in students' class preparation, note-taking, and examination preparation over the course of professional school. This study aims to describe the use of these learning and study strategies by pharmacy students and to analyze changes during their education.Methods. We performed a prospective, observational cohort study of students at a single US pharmacy school from 2016-2019. Students completed an online survey on learning and study strategies at the beginning of each school year. Quantitative results were analyzed by level in pharmacy school during which the survey was completed as the primary predictor. Open-ended responses were thematically analyzed using an inductive approach.Results. We observed significant changes in strategies, including an increased use of audiovisual materials for course preparation, preference for electronic over manual notetaking, increasing use of lecture capture viewing, and increased use of peer materials in studying. Changes were generally largest between students' first (P1) and second (P2) years in pharmacy school, representing adjustments in student behaviors during the P1 year. In some cases, changes from the surveys in the P1 to P2 years were followed by a gradual return toward P1 survey levels. Three themes described students' comments: students' preferences shaped their learning strategies, their experiences guided changes in learning strategies, and they used additional strategies beyond those included in the survey items.Conclusions. Significant changes in pharmacy student study strategies occurred over the course of their education. This may represent an opportunity to promote use of more effective approaches for long-term learning.

Student Performance Outcomes and Perceptions in Two Content Areas in Conventional Versus Integrated Pharmacy Curricula.

Objective. To compare student performance measures and perceptions of learning in 2 content areas, conventional and integrated pharmacy curricula, at a single institution.Methods. Prospective cohort study of pharmacy students enrolled in either conventional (cohort C) or integrated (cohort I) curricula. Summative examination performance in the neuropsychiatric and infectious diseases courses, student self-rating of confidence and comfort in integrating and applying knowledge, and performance on a delayed knowledge assessment were compared between cohorts.Results. Cohort I students performed significantly lower on summative assessments compared to cohort C (78.4±9.1 vs 84.5±8.3, respectively). Prior to the integrated course, cohort I students rated themselves as significantly less confident and comfortable in knowledge integration, application, and communication compared to cohort C students; these differences were attenuated in a follow-up survey, although some remained significant. There was no difference between cohorts in performance on objective structured clinical examinations (OSCEs) or on a delayed knowledge assessment of neuropsychiatric and infectious diseases content.Conclusion. Pharmacy students in an integrated curriculum initially performed modestly worse in summative assessments and self-assessed their baseline knowledge as lower than did students in a conventional curriculum. However, differences in self-rated knowledge decreased at follow-up, and performance of the two cohorts on OSCEs and a delayed examination was similar. As pharmacy curricula shift towards integrated models, institutions should also consider evaluating experiential performance outcomes and student motivation to fully assess the impact of these transitions.

Acetaminophen inhibits cytochrome c redox cycling induced lipid peroxidation.

Cytochrome (cyt) c can uncouple from the respiratory chain following mitochondrial stress and catalyze lipid peroxidation. Accumulating evidence shows that this phenomenon impairs mitochondrial respiratory function and also initiates the apoptotic cascade. Therefore, under certain conditions a pharmacological approach that can inhibit cyt c catalyzed lipid peroxidation may be beneficial. We recently showed that acetaminophen (ApAP) at normal pharmacologic concentrations can prevent hemoprotein-catalyzed lipid peroxidation in vitro and in vivo by reducing ferryl heme to its ferric state. We report here, for the first time, that ApAP inhibits cytochrome c-catalyzed oxidation of unsaturated free fatty acids and also the mitochondrial phospholipid, cardiolipin. Using isolated mitochondria, we also showed that ApAP inhibits cardiolipin oxidation induced by the pro-apoptotic protein, tBid. We found that the IC(50) of the inhibition of cardiolipin oxidation by ApAP is similar in both intact isolated mitochondria and cardiolipin liposomes, suggesting that ApAP penetrates well into the mitochondria. Together with our previous results, the findings presented herein suggest that ApAP is a pleiotropic inhibitor of peroxidase catalyzed lipid peroxidation. Our study also provides a potentially novel pharmacological approach for inhibiting the cascade of events that can result from redox cycling of cyt c.

Should multiple-choice questions get the SAQ? Development of a short-answer question writing rubric.

INTRODUCTION: Short-answer questions (SAQs) are often used to assess pharmacy student competency. However, the literature lacks guidance on SAQ development strategies, resulting in varying practices between SAQ writers. Understanding student and faculty perceptions of what constitutes a high-quality SAQ can identify best practices for SAQ development. METHODS: We surveyed second-year pharmacy students at the University of California San Francisco (UCSF) to assess their perceptions of SAQs. Likert-type data were descriptively analyzed, and open-ended responses were analyzed using thematic analysis; we used these results to draft an initial SAQ checklist. We then conducted focus groups of UCSF pharmacy faculty to explore their experiences writing SAQs. Transcripts were analyzed using the survey codebook and de novo codes to generate themes. We used the focus group findings to finalize the checklist. RESULTS: Seventy-five students (82%) completed the survey. Students identified "structure" (organizing into sections/lists) and "content" (clearly delineating student's task) as two ways to improve SAQ quality. Eight faculty participated in focus groups of two to three participants each. Faculty expanded on these previous themes and also identified a new theme, "process." This included peer review of SAQs as well as the iterative process involved in writing the SAQ, model answer, and grading rubric. CONCLUSIONS: Content, structure, and process were the three areas identified for the improvement of SAQ quality at our institution. A checklist outlining best practices in these areas may be best implemented and adopted within the SAQ peer-review process.

Longitudinal study of grit among pharmacy students: Impact of cohort and professional year.

INTRODUCTION: Whether grit changes over a student's enrollment in health professions school is unknown. We aimed to measure grit across 13 cohort-years of students in a four-year doctor of pharmacy (PharmD) program. METHODS: We administered the Short Grit Scale (Grit-S) to first-year (P1), second-year (P2), third-year (P3), and fourth-year (P4) PharmD students between 2016 and 2019. There was no intervention aimed at increasing grit. RESULTS: A total of 1381 responses were recorded across 624 students (86.5% response rate). Across all graduation cohorts, Grit-S scores significantly decreased by an average of 0.087 points from P1 to P2 (P = .004), increased significantly from P2 to P3 by 0.09 points (P < .001), and nominally increased from P3 to P4 by 0.023 points (P = .45). Between cohort differences in paired Grit-S scores only differed significantly for P3 to P4 (P = .03) and P1 to P3 (P = .01) years. A mixed-effects linear regression model clustered on graduation cohort and individual student found that mean Grit-S scores in the P2 year were - 0.1 points lower than those in the P1 year (P < .001). However, differences between P3 and P1 (-0.04, P = .17) and between P4 and P1 (-0.03, P = .37) were not statistically significant. CONCLUSIONS: In the absence of a specific intervention, statistically significant changes in Grit-S scores occur over the course of a pharmacy school curriculum. The P1 year may be associated with a decline in grit, although by the P4 year Grit-S scores return to baseline.

Examining participant perceptions of the UCSF school of pharmacy master preceptor program.

INTRODUCTION: The University of California San Francisco School of Pharmacy faculty created the Master Preceptor Program (MPP) to instill best practices in clinical precepting, leadership and professional development, and interprofessional education (IPE). Graduates of the program are encouraged to mentor colleagues at affiliated sites. This study aimed to explore MPP participants' perceptions about the program and to collect general feedback. METHODS: A descriptive qualitative study of MPP participants who completed the program between 2017 and 2019 was conducted. Semi-structured interviews and focus groups were used to collect general programmatic feedback and examples of skill implementation. All encounters were conducted and recorded online via Zoom. Three investigators independently analyzed transcripts for codes related to key programmatic areas using conventional content analysis. RESULTS: Ten of 14 past MPP participants participated. Themes included confidence and skills gained in clinical teaching, self-reflection and network opportunities supporting professional and leadership development, and a need for structured expectations and deliverables. Participants noted several benefits of the MPP on clinical teaching, such as improving confidence and adopting teaching techniques, structural and organizational skills, and a learner-centered approach. Participants also mentioned programmatic offerings that improved leadership and professional development, such as networking opportunities in the MPP and at conferences. Participants did not mention IPE in their responses. CONCLUSIONS: All participants recognized the MPP as an effective training program to enhance clinical precepting skills, leadership, and professional development. Program structure and intentional incorporation of IPE skills are areas of improvement for future cohorts.

Impact of an auditory hallucination simulation coupled with a speaker diagnosed with schizophrenia on mental illness stigma in pharmacy students.

INTRODUCTION: Hallucination simulations improve student empathy but increase desired social distance from individuals with schizophrenia, while direct contact reduces social distance. This study describes the implementation of combining an auditory hallucination simulation with a speaker diagnosed with schizophrenia and its impact on mental illness stigma. METHODS: Pharmacy students in their last year of didactic instruction (N = 346) attended a presentation by a speaker diagnosed with schizophrenia then participated in a hallucination simulation. Mental illness stigma was measured before and after the intervention using the Opening Minds Survey for Health Care Professionals (OMS-HC). Related-samples Wilcoxon-signed rank tests were used to evaluate changes in OMS-HC scores. An inductive qualitative analysis was conducted on student perceptions of patients with psychosis. RESULTS: OMS-HC total scores were reduced by an average of 2.0 ± 5.6 (P = .005) for the first-year pilot and 2.3 ± 7.0 (P < .001) for the subsequent year. OMS-HC attitudes (P = .005) and disclosure/help-seeking (P < .005) subscales decreased both years. There was no significant change in the social distance subscale (P = .205) the first year and a significant decrease (P = .015) the second year. The themes identified from the open-ended comments were increased awareness, sympathy, empathy, inspiration/admiration, discomfort, and change to patient care. CONCLUSIONS: The combination of a speaker with schizophrenia and auditory hallucination simulation effectively reduced mental illness stigma. The combination is likely effective for reducing stigmatizing attitudes and willingness to disclose mental illness with variable reduction in desired social distance.

Gaps in Patient Education on Safe Handling and Disposal of Oral Chemotherapy Drugs: A Pilot Prospective Cohort Survey Study.

Background: Oral anticancer chemotherapy (OC) has been misperceived as being safer than intravenous chemotherapy, leading to its increased risk of improper handling and disposal. This survey study assessed the knowledge, practices and attitudes of pharmacists and patients regarding OC handling and disposal, gaps in knowledge and barriers to patient education. Methods: Surveys were developed based on literature review and pilot study validation results. Patients completed a 33-item paper or electronic survey whereas pharmacists completed a 38-item electronic survey. Descriptive statistics and Fisher's exact test computed using the R Project were used for analyses. Results: Pharmacist group (16/25, 62.5%) and patient group (14/29, 48.3%) believed that the oral route is safer than IV. Average overall correct response rates for pharmacist and patient groups were 78.3% and 61.9%, respectively. Significant gaps in knowledge between groups were observed in three sections (p < 0.05). Common barriers to providing patient education were insufficient training (70.8%) and insufficient time (50%). Conclusion: Pharmacist and patient knowledge, awareness and practices of OC safe handling and disposal are suboptimal. Areas of knowledge gaps and barriers to patient education were identified. Enhanced supports are needed to empower pharmacists to assume an active role in patient education on safe handling and disposal of OC.

Exploring Multiple Perspectives on Pharmacy Students' Readiness for Advanced Pharmacy Practice Experiences.

Objective. This study aimed to enrich the Academy's understanding of pharmacy students' readiness for advanced pharmacy practice experiences (APPEs) by exploring the perspectives of three primary stakeholders: APPE students, APPE preceptors, and APPE faculty site directors.Methods. A descriptive qualitative study of APPE readiness was conducted using workplace learning as a guiding conceptual framework. Data were collected between March and September 2019 through semi-structured focus groups and interviews with students (five groups), preceptors (four groups), and faculty site directors (one group, two individual interviews). The data were analyzed using directed content analysis.Results. Participants described APPE readiness as a multifaceted construct comprised of four themes: learner characteristics, participation in workplace activities, relationship-building, and workplace practices to orient and support students. While all participants addressed each category, faculty site directors and preceptors tended to focus on learner characteristics, while students emphasized their participation in the workplace and relationship building.Conclusion. Knowledge is widely recognized as a requirement for APPE readiness. This study identified learner characteristics, workplace participation, and relational skills as additional requirements. Some of these criteria are challenging to assess prior to APPEs, which makes orienting students both prior to and at the start of APPEs particularly important to support readiness. Thus, a comprehensive review of APPE readiness might also include assessing the readiness of workplaces, administrators, and preceptors for APPE students.

A Randomized, Crossover Pilot Study of a Novel Web-Based/Mobile Platform for Collaborative Small Group Practice in Therapeutic Reasoning.

BACKGROUND AND PURPOSE: Therapeutic reasoning-the mental process of making judgments and decisions about treatment-is developed through acquisition of knowledge and application in actual or simulated experiences. Health professions education frequently uses collaborative small group work to practice therapeutic reasoning. This pilot study compared the impact of a web-based/mobile tool for collaborative case work and discussion to usual practice on student perceptions and performance on questions designed to test therapeutic knowledge and reasoning. METHODS: In a therapeutics course that includes case-based workshops, student teams of 3 to 4 were randomly assigned to usual workshop preparation (group SOAP sheet) or preparation using the Practice Improvement using Virtual Online Training (PIVOT) platform. PIVOT was also used in the workshop to review the case and student responses. The next week, groups crossed over to the other condition. Students rated favorability with the preparatory and in-workshop experiences and provided comments about the PIVOT platform via a survey. Student performance on examination items related to the 2 workshop topics was compared. RESULTS: One hundred and eleven students (94%) completed post-workshop surveys after both workshops. The majority of students (57%) preferred using the PIVOT platform for workshop collaboration. Favorability ratings for the in-workshop experience did not change significantly from first to second study week, regardless of sequence of exposure. There was no relationship between examination item scores and the workshop platform the students were exposed to for that content (P = .29). Student responses highlighted the efficiency of working independently before collaborating as a group and the ability to see other students' thought processes as valuable aspects of PIVOT. Students expressed frustration with the PIVOT user interface and the lack of anonymity when discussing their answers in the workshop. CONCLUSION: A web-based/mobile platform for student team collaboration on therapeutic reasoning cases discussed in small group settings yielded favorable ratings, examination performance comparable to standard approaches, and was preferred by a majority of students. During the rapid shift to substantial online learning for the COVID-19 pandemic, virtual collaboration tools like PIVOT may help health professions teachers to better support groups working virtually on scaffolded therapeutic reasoning tasks.

A novel online platform promotes asynchronous class preparation and thought transparency.

BACKGROUND AND PURPOSE: Engaging all learners with self-directed class preparation materials can be challenging. The purpose of this study is to assess student perceptions of a novel app and web-based program, Practice Improvement using Virtual Online Training (PIVOT) as a preparatory tool in a pharmacy therapeutics course. EDUCATIONAL ACTIVITY AND SETTING: PIVOT was designed to encourage self-directed information gathering, group collaboration, and problem-solving prior to classes. Students accessed PIVOT to obtain patient information and provide responses to questions. A semi-structured large group case discussion, facilitated by the instructor, followed the preparatory assignment. All students were invited to participate in pre-/post-activity online surveys to evaluate their experiences. FINDINGS: One hundred and ten students (92.4%) completed both surveys. Students identified viewing/comparing answers with classmates (73%), enforcing preparation (51%), and asynchronous preparation (51%) as useful aspects of PIVOT. Working with a group (42%) and organizing patient information (32%) were selected as negative aspects of PIVOT. More than half of students preferred not to use PIVOT for class preparation, but 41% of students would like to see PIVOT integrated in their therapeutics courses. SUMMARY: Integrating PIVOT into a pharmacy therapeutics course resulted in mixed student perceptions. Several helpful aspects of this platform were identified and a majority suggested drawbacks that are also common features of actual pharmacy practice. Implementing PIVOT in a different learning context may improve student perceptions.

Longitudinal Associations Between Grit, Academic Outcomes, and Residency Match Rates Among Pharmacy Students.

Objective. To characterize Grit-S scores in pharmacy students, determine whether Grit-S scores change within individual pharmacy students and cohorts over time, and investigate the relationship between Grit-S scores, academic outcomes, and professional outcomes. Methods. A survey was conducted in fall 2016 and again in fall 2017 to determine Grit-S scores in first- through fourth-year pharmacy students. Participant demographic variables, grade point average (GPA), advanced pharmacy practice experience (APPE) ratings, and residency match results were collected. Results. Over the study period, 852 survey responses were completed by 85% of students surveyed. The mean Grit-S scores of each cohort ranged from 3.5 to 3.7 (on a 5-point scale with 5 representing the highest level of grit). Underrepresented minorities had slightly higher Grit-S scores and first-generation college students had slightly lower Grit-S scores. Two hundred eighty-seven students responded to both the 2016 and 2017 surveys. Among these paired responses, small but significant changes in individual Grit-S scores over time that varied in direction and magnitude by school year were noted. Higher Grit-S scores were not associated with higher GPA or superior APPE performance, nor were they predictive of a student matching to a postgraduate pharmacy residency. Conclusion. Significant associations between grit and measures of academic or professional achievement were not detected in this pharmacy student cohort. The presence of small but significant changes in Grit-S scores over time, in the absence of any intervention, has implications that further research should be conducted in this area.

A Comprehensive Survey of Infectious Diseases Curriculum Among US Pharmacy Schools.

Objective. To describe what and how infectious diseases (ID) topics are taught in US schools of pharmacy and summarize pharmacy faculty members' and students' perceived successes and challenges in teaching and learning about ID. Methods. A 23-item survey instrument was distributed electronically to ID faculty members at 137 US pharmacy schools. Data collected included curricular hours and format, topics covered, active-learning strategies, and curricular successes and concerns. Results. Surveys were collected from 106 schools (77% response rate). Infectious diseases curricula were allotted a median of 60 (IQR=40) hours of classroom time. Respondents dedicated 33% of curriculum hours to ID fundamentals and 66% to disease states. Greater than 94% of schools taught all tier one ID topics from the 2016 American College of Clinical Pharmacy Pharmacotherapy Didactic Curriculum Toolkit. Curricula were primarily delivered through traditional lectures rather than active learning (75% vs 25% of classroom time, respectively). The median number of active-learning strategies used was four (IQR=3). The most common active-learning modalities used either consistently or frequently were patient case application (98%) and audience response systems (76%). The most common successes cited by faculty members were implementation of active learning, the "real-world" applicability of the ID topics, and the breadth of topics and topic exposure covered in the curriculum. The most common concerns were a lack of time to cover material and the amount of material covered. Conclusion. Increased communication and collaboration between ID educators is warranted to increase consistency of ID education and distribution of educational innovations.

Multidrug-Resistant Pseudomonas Infections: Hard to Treat, But Hope on the Horizon?

PURPOSE OF REVIEW: As the sixth most common nosocomial pathogen in the USA, Pseudomonas aeruginosa poses a significant threat to patients within the healthcare system. Its intrinsic and acquired resistance mechanisms also significantly limit the choices for antimicrobial therapy, prompting an increase in the research and development of antibacterial agents with enhanced activity against multidrug-resistant (MDR) P. aeruginosa. While many approved and pipeline antibiotics have activity against wild-type P. aeruginosa, only four new antibiotics have promising activity against MDR P. aeruginosa: ceftazidime-avibactam (Avycaz®), ceftolozane-tazobactam (Zerbaxa®), cefiderocol, and imipenem-cilastatin/relebactam. The goal of this paper is to review the epidemiology and mechanisms of resistance in P. aeruginosa as well as explore the newly approved and pipeline agents that overcome these mechanisms of resistance. RECENT FINDINGS: Ceftazidime-avibactam and ceftolozane-tazobactam are currently FDA-approved and available for use, while cefiderocol and imipenem-cilastatin/relebactam are in development. Current evidence suggests ceftazidime-avibactam and ceftolozane-tazobactam both may have a role in treatment of MDR P. aeruginosa infections. Ceftolozane-tazobactam appears to be modestly more potent against P. aeruginosa, but emergence of resistance has been noted in various reported cases. Trials are ongoing for cefiderocol and imipenem-cilastatin/relebactam and early results appear promising. The aforementioned agents fill important gaps in the antibiotic armamentarium, particularly for patients with MDR P. aeruginosa infections who otherwise have extremely limited and often toxic antibiotic options. However, resistance to all of these agents will likely emerge, and additional antibiotic development is warranted to provide sufficient options to successfully manage MDR P. aeruginosa infections.

Sustainable Pharmacy: Piloting a Session on Pharmaceuticals, Climate Change, and Sustainability within a U.S. Pharmacy Curriculum.

OBJECTIVE: To design and assess an innovative session for pharmacy students that addresses the role of pharmaceuticals with climate change and sustainability. INNOVATION: One hundred and sixteen third-year students at the University of California, San Francisco School of Pharmacy participated during their required Health Policy course. This 3-hour session included guided pre-course activities, an interactive lecture, a panel of healthcare professionals discussing complex decision-making and small group case-based learning. Curricular assessment was conducted through pre-/post-test measures of knowledge acquisition, student evaluations, and course projects. CRITICAL ANALYSIS: One hundred and two students (response rate 88%) completed the pre-test and 115 students (response rate 99%) completed the post-test assessment. We identified a significant increase in the proportion of correct answers on post-test questions addressing drug disposal legislation (75% pre-test vs 91% post-test, p=0.002) and the predicted effects of climate change on health (55% pre-test vs 90% post-test, p < 0.001). The session was also well received; average student evaluation scores were above 4 in all areas of course evaluation (where 5=ideal). In addition, 17% of student groups (relative to 0% in 2015) proposed a sustainability-related policy as their final coursework project. NEXT STEPS: The development and implementation of this brief session resulted in knowledge gain and favorable student response. This project is feasible for other Schools of Pharmacy to adapt and implement.

New approaches in primary central nervous system lymphoma.

Primary central nervous system lymphoma (PCNSL) has long been associated with an inferior prognosis compared to other aggressive non-Hodgkin's lymphomas (NHLs). However, during the past 10 years an accumulation of clinical experience has demonstrated that long-term progression-free survival (PFS) can be attained in a major proportion of PCNSL patients who receive dose-intensive consolidation chemotherapy and avoid whole brain radiotherapy. One recent approach that has reproducibly demonstrated efficacy for newly diagnosed PCNSL patients is an immunochemotherapy combination regimen used during induction that consists of methotrexate, temozolomide, and rituximab followed by consolidative infusional etoposide plus high-dose cytarabine (EA), administered in first complete remission (CR). Other high-dose chemotherapy-based consolidative regimens have shown efficacy as well. Our goal in this review is to update principles of diagnosis and management as well as data regarding the molecular pathogenesis of PCNSL, information that may constitute a basis for development of more effective therapies required to make additional advances in this phenotype of aggressive NHL.