Design, Synthesis, and Preliminary Evaluation of [68Ga]Ga-NOTA-Insulin as a PET Probe in an Alzheimer's Disease Mouse Model.

Aberrant insulin signaling has been considered one of the risk factors for the development of Alzheimer's disease (AD) and has drawn considerable attention from the research community to further study its role in AD pathophysiology. Herein, we describe the development of an insulin-based novel positron emission tomography (PET) probe, [68Ga]Ga-NOTA-insulin, to noninvasively study the role of insulin in AD. The developed PET probe [68Ga]Ga-NOTA-insulin showed a significantly higher uptake (0.396 ± 0.055 SUV) in the AD mouse brain compared to the normal (0.140 ± 0.027 SUV) mouse brain at 5 min post injection and also showed a similar trend at 10, 15, and 20 min post injection. In addition, [68Ga]Ga-NOTA-insulin was found to have a differential uptake in various brain regions at 30 min post injection. Among the brain regions, the cortex, thalamus, brain stem, and cerebellum showed a significantly higher standard uptake value (SUV) of [68Ga]Ga-NOTA-insulin in AD mice as compared to normal mice. The inhibition of the insulin receptor (IR) with an insulin receptor antagonist peptide (S961) in normal mice showed a similar brain uptake profile of [68Ga]Ga-NOTA-insulin as it was observed in the AD case, suggesting nonfunctional IR in AD and the presence of an alternative insulin uptake route in the absence of a functional IR. The Gjedde-Patlak graphical analysis was also performed to predict the input rate of [68Ga]Ga-NOTA-insulin into the brain using MicroPET imaging data and supported the in vivo results. The [68Ga]Ga-NOTA-insulin PET probe was successfully synthesized and evaluated in a mouse model of AD in comparison with [18F]AV1451 and [11C]PIB to noninvasively study the role of insulin in AD pathophysiology.

Plasma exchange as treatment for osmotic demyelination syndrome: Case report and review of current literature.

Osmotic demyelination syndrome (ODS) is characterized by widespread degeneration of myelin within the central nervous system and has no established treatment. A limited number of cases have reported positive outcomes with plasma exchange in the treatment of ODS associated with chronic alcohol abuse or liver transplantation. We report the case of a 23-year-old female presenting with ODS following rapid correction of hyponatremia, which was attributed to hypoalbuminemia, volume overload, and malnutrition secondary to ulcerative colitis. Our patient received four plasma exchange sessions over the course of five days for a total plasma exchange of 15,500 mL. Unfortunately, the patient did not achieve significant neurologic recovery following completion of the plasma exchange regimen. This is the first report of the failure of this novel approach in the management of a patient with ODS, suggesting benefit in a limited patient population. We describe the proposed mechanism of plasma exchange in the treatment of ODS and provide a review of existing literature.

The Impact of Capping Creatinine Clearance on Achieving Therapeutic Vancomycin Concentrations in Neurocritically Ill Patients with Traumatic Brain Injury.

BACKGROUND: Traumatic brain injury (TBI) is associated with secondary complications, including infection, and patients with TBI often exhibit augmented renal clearance (ARC). This phenomenon has been associated with subtherapeutic levels of renally cleared drugs such as vancomycin, which is dosed based on body weight and creatinine clearance (CrCl). Many clinicians, however, cap CrCl at 120 mL/min/1.73 m2 when calculating vancomycin dosing regimens. We hypothesize that capping patient CrCl, as opposed to utilizing the non-capped CrCl, when determining vancomycin dosing schemes results in subtherapeutic serum trough concentrations in patients with TBI. METHODS: This was a retrospective study of adult patients with TBI admitted between April 2014 and December 2015 who received vancomycin. Population-based pharmacokinetic (PK) parameters using non-capped calculated CrCl and capped CrCl were compared with patient-specific PK parameters based on serum trough concentrations. RESULTS: Thirty-two patients with TBI were included in the study. ARC was suspected in 24 (75%) patients due to a median estimated CrCl at serum trough concentration of 167.3 (127.7-197.7) mL/min. The mean dosing regimen was 17.1 (13.2-19.2) mg/kg every 8 (8-8) h. There was no difference between the median measured trough concentration and predicted value using non-capped CrCl [10.4 (7.1-15.0) vs. 11.5 (7.8-13.7) mcg/mL; p = 0.7986]. The median measured trough concentration was significantly lower than the predicted trough concentration when calculated based on capping the CrCl at 120 mL/min/1.73 m2 [16.3 (15.3-22.0) vs. 11.5 (7.8-13.7) mcg/mL; p < 0.0001]. CONCLUSIONS: Patients with traumatic brain injury appeared to exhibit augmented renal clearance, leading to subtherapeutic vancomycin serum trough concentrations when doses were calculated using the traditional method of capping creatinine clearance at 120 mL/min/1.73 m2. Instead, utilizing patients' non-capped creatinine clearance when determining a vancomycin dosing regimen is more accurate and provides a better estimation of vancomycin pharmacokinetics and could be applied to other renally excreted medications.

Use of a clinical reasoning scaffolding document improves student performance.

OBJECTIVE: Clinical reasoning is an essential skill set for practicing pharmacists to possess. Given its complex nature, optimal pedagogies for teaching clinical reasoning are largely unknown. The use of scaffolding to expand a student's zone of proximal development and improve clinical reasoning performance was assessed in this study. METHODS: This prospective, observational cohort study of second professional year (P2) students compared performance of those who were exposed to a clinical reasoning scaffolding tool (CRST) to historic control P2 students (No CRST) on FARMR notes in alignment with the Pharmacists' Patient Care Process. Student performance was assessed using an entrustment-like scale for each of 5 sections (Findings, Assessment and goals, Recommendations, Monitoring, and Rationale) of the FARMR to link classroom and experiential education settings. RESULTS: In total, 141 CRST students from 28 groups were compared to 77 No CRST students from 13 groups. CRST students performed significantly higher in Assessment and goals of therapy, Recommendations, Monitoring, Rationale sections but no difference in Findings. CONCLUSIONS: Scaffolding has been utilized successfully in other health professions education. This study provides evidence of it successfully improving student pharmacist clinical reasoning skills, an essential ability for successful pharmacy practitioners.

Student Pharmacists Provide Similar Quality Clinical Reasoning Feedback as Resident Teaching Assistants.

OBJECTIVE: Pharmacists utilize clinical reasoning (CR) to improve patient outcomes via medication optimization. It is critical to develop these skills in student pharmacists, yet optimal pedagogies to teach and assess CR are unknown. Peer feedback may be used to develop CR in student pharmacists, but a certain feedback quality must be reached to be effective. This study sought to evaluate if student pharmacists could provide similar quality peer feedback compared to pharmacy resident teaching assistant (TA) feedback. METHODS: This was a retrospective, mixed-methods pedagogical analysis comparing the quality of first-year student pharmacist peer feedback to resident TA CR feedback. The CR comments were defined using the intellectual standards of CR. Quality was assessed for task specification, gap identification, actionability, and process orientation by 2 independent investigators. Student performance and perceptions were also assessed. Mann-Whitney U, t tests, and descriptive statistics were used to analyze data where appropriate. RESULTS: Clinical reasoning feedback from peers (N = 805) and TAs (N = 206) were analyzed. Interrater reliability for feedback quality was moderate to substantial. Overall, peer CR feedback was of higher quality regarding task specification and process orientation while TA CR feedback was of higher quality regarding gap identification and actionability. Students receiving peer feedback performed better on a final patient case than those receiving TA feedback (95.2% vs 92.3%). Overall, the peer feedback process was well received by students. CONCLUSION: Student pharmacists can provide similar quality feedback as resident TAs. Peer feedback offers an alternative to resident TA feedback and has the potential to contribute to improved CR skills.

Evaluating the Need for Competency-Based Pharmacy Education (CBPE): The Report of the 2023-2024 Academic Affairs Standing Committee.

The 2023-2024 Academic Affairs Committee was charged to create a sense of urgency around the concept of Competency-Based Pharmacy Education and develop a "readiness for change" instrument that is based on the 5 essential elements that make up the definition of Competency-Based Pharmacy Education. This report describes the process undertaken by the committee to determine the societal needs of pharmacists and current state of pharmacy practice and pharmacy education. The practice gaps in pharmacy education and the key drivers needed to close these gaps are evaluated. To complete the charges, the committee conducted evidence-based literature reviews and completed a series of focus groups with stakeholders and thought leaders with experience in competency-based education.

Analysis of Expert Feedback to Determine Intellectual Standards for Student Pharmacist Clinical Reasoning Development.

Objectives. Clinical reasoning (CR) is one of the most important skills for pharmacy learners. Feedback has been proposed as a pedagogy to improve CR skills; however, essential components of CR have yet to be determined within pharmacy education. This study sought to streamline feedback to align with the Pharmacists' Patient Care Process (PPCP).Methods. The investigators used deidentified clinical reasoning "Keep," "Start," or "Stop" (KSS) feedback comments from student-written CR "think-aloud" sessions with pharmacy students in their third professional year. Sections were mapped to the PPCP and were coded by 2 independent investigators according to proposed essential components of CR, using an adapted grounded-theory approach. Investigators could inductively add codes after conferring with the other. Coded feedback was analyzed using a summative content approach. Intercoder reliability was calculated via Holsti index.Results. Five essential components of CR were identified after analysis of 635 KSS comments. The 5 essential components of CR were coded 1178 times. "Accurate," "Concise," "Specific," and "Thorough" were identified a priori, while "Connected" was discovered during feedback comment review. Literature analysis added supporting data to these results through the Paul-Elder Critical Thinking Framework. To maintain consistency in language, these essential components will be referred to as "intellectual standards" moving forward.Conclusion. This novel study successfully identified 5 key intellectual standards of CR. These intellectual standards provide a framework for pharmacy educators to focus feedback to improve student CR. Future research of other intellectual standards pertinent to experiential education is imperative.

Augmented Renal Clearance in the Hematology and Oncology Populations: A Scoping Review for Pharmacists.

INTRODUCTION: Until recently, interest in renal function has focused on impairment to limit drug toxicity and increase medication safety. Augmented renal clearance (ARC) has been increasingly studied in multiple patient populations, including oncology, and could lead to decreased drug efficacy from faster elimination resulting in subtherapeutic concentrations. This scoping review sought to summarize ARC literature in cancer and identify areas of research to better inform pharmacy practitioners. DATA SOURCES: Electronic databases were searched for English articles related to augmented/enhanced renal function/clearance following a framework for scoping reviews. DATA SYNTHESIS: Fourteen articles were analyzed, divided according to article objective: descriptive studies or ARC's impact on pharmacokinetics/pharmacodynamics. ARC was most defined as creatinine clearance >130 mL/min/1.73 m2, reported in 10%-100% of patients. Febrile neutropenia in adult and pediatric patients, and age <50-65 years, hematologic malignancy, and lower serum creatinine in adult patients were notable risk factors for ARC. The impact of ARC has only been evaluated with antimicrobial agents consistently resulting in lower than anticipated trough levels. Identified gaps include: elucidation of ARC's mechanism and associated biomarkers, an inclusive ARC definition for relative renal enhancement, and study of additional drug classes to ascertain the breadth of ARC impact on drug therapy. CONCLUSIONS: ARC is proving to be a frequent phenomenon in patients with cancer which pharmacists could play a vital role. Further research is needed to better understand the impact of ARC in patient care and a potential need to stage ARC based on degree of renal enhancement to establish specific drug dosing recommendations.

Augmented Renal Clearance: An Under-Recognized Phenomenon Associated With COVID-19.

Augmented renal clearance (ARC) is a phenomenon that has been described mainly in critically ill patients and is characterized by increased creatinine clearance and elimination of renally cleared medications that could place patients at risk of therapeutic failure. The COVID-19 pandemic has led to an overwhelming number of ICU admissions with many reports of the impact of COVID-19 on the kidney. This report aims to increase clinician awareness of, and risk factors for ARC in patients with COVID-19, especially in comparison to other critical illnesses.

Use of journal clubs and book clubs in pharmacy education: A scoping review.

BACKGROUND: Journal clubs and book clubs are educational activities used in health sciences education to teach evidence-based decision-making, critical thinking, and appraisal skills, and build trainee understanding about important professional issues. The main objective of this scoping review was to identify and synthesize all research studies on journal or book clubs for pharmacy learners. A secondary objective was to identify gaps in the literature where future research would be beneficial to pharmacy educators and learners. METHODS: A comprehensive literature search was run across five databases. Studies were screened using a two stage, blinded, independent screening process. RESULTS: Forty-two studies met all inclusion criteria; 86% reported on journal clubs and 14% on book clubs. Of the journal club studies, 50% were in didactic courses, 33% in experiential education, and 17% were co-curricular initiatives. Of the six book club studies, 67% were within didactic courses and 33% were co-curricular initiatives, including the only interprofessional education study. Most journal clubs were used to teach evidence-based practice, drug literature evaluation, or biostatistics. Book clubs were more focused on soft skills or topics students were less likely to encounter in the core curriculum. IMPLICATIONS: Future research on journal clubs and book clubs in pharmacy education should continue to assess student learning outcomes and abilities. Specifically, future studies should move beyond evaluating student perceptions of journal clubs to investigate effectiveness for topics other than drug literature evaluation or evidence-based practice, and the impact of journal clubs and book clubs on interprofessional knowledge, communication, and team dynamics.

Scoping review of augmented renal clearance in critically ill pediatric patients.

Augmented renal clearance (ARC), a phenomenon of enhanced elimination of renal solutes, has been described in adult critically ill patients, but little is known about the phenomenon in children. The aim of this scoping review was to gather and summarize all evidence on ARC in pediatric patients to examine its breadth and depth including prevalence, risk factors, and pharmacokinetic alterations and identify any gaps for further areas of inquiry. PubMed, Embase, and Web of Science were searched for titles, abstracts, or keywords that focused on ARC. Non-English studies, reviews, and nonhuman studies were excluded. Reporting followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Reviews (PRISMA-ScR) guidelines. Data were extracted on article type, study details, patient population, ARC definition and prevalence, methods of renal function assessment, and study results. A total of 215 citations were found with 25 citations meeting the criteria for inclusion in pediatrics (2102 total patients); the majority of studies (84%) focused on pharmacokinetics (PK) of antimicrobial agents. The median/mean age range was 1.25-12 years. There were a total of 10 different definitions of ARC. The prevalence of ARC ranged from 7.8% to 78%. The most common method for documenting creatinine clearance (CrCl) was the modified Schwartz equation (64%). Only 20% of studies reported risk factors for ARC including low serum creatinine, increasing age, febrile neutropenia, male, septic shock, and treatment with antibiotics. Glycopeptide antimicrobials were the most evaluated class (42.9%) among the 21 antimicrobial drug studies. All studies reported increased drug clearance and/or poor probability of achieving target concentrations of the agents studied. ARC showed variable prevalence in pediatric patients likely due to the lack of a standard definition and many studies not considering age-related changes in CrCl with pediatric intensive care unit (PICU) patients. ARC was shown to impact PK of antibiotics commonly administered to pediatric patients, which may necessitate changes in standard dosing regimens.

Feedback for Learning in Pharmacy Education: A Scoping Review.

Feedback is an effective pedagogy aimed to create cognitive dissonance and reinforce learning as a key component of clinical training programs. Pharmacy learners receive constant feedback. However, there is limited understanding of how feedback is utilized in pharmacy education. This scoping review sought to summarize the breadth and depth of the use of feedback within pharmacy education and identify areas for future research. PubMed, Embase, Scopus, and Web of Science were searched for English articles since January 2000 to identify studies related to feedback in pharmacy education. Sixty-four articles were included for analysis, stratified by moderate and major theory talk, where moderate theory talk explicitly included feedback into study design and major theory talk included feedback into both study design and analysis. Feedback was provided in Bachelor (14%), Master (15.6%), Doctor of Pharmacy (67.2%) and post-graduate programs (4.7%) on a variety of curricular objectives including communication and patient work up in didactic, objective structured clinical examination (OSCE), and experiential settings, and career/interview preparation in the co-curriculum. Feedback comments were mostly written in didactic courses, and both written and verbal in OSCE, experiential, and co-curricular settings. The pharmacy education feedback literature lacks depth beyond student perceptions, especially with respect to assessing the effectiveness and quality of feedback for learning. While feedback has been utilized throughout pharmacy education across myriad outcomes, several areas for inquiry exist which can inform the design of faculty and preceptor development programs, ensuring provision of effective, quality feedback to pharmacy learners.

A Scoping Review of the Pharmacy Curriculum Outcomes Assessment Literature.

Objective. To identify themes, gaps, and sources of evidence from the literature regarding the Pharmacy Curriculum Outcomes Assessment (PCOA) to inform practice and additional areas for research in pharmacy education.Findings. Nineteen articles describing the administration and use of PCOA were identified. Since PCOA was made a curricular requirement by the Accreditation Council of Pharmacy Education in 2016, the focus of literature related to the PCOA has shifted from administration practices (four articles published before 2016 vs two articles published since) to determining models that may predict student performance on the assessment (two vs five articles) or how the examination might be used to predict future performance (one vs seven articles), especially on the North American Pharmacist Licensing Examination. While there is a growing body of literature focused on the PCOA's utility for measuring performance, few variables have been consistently used.Summary. This review found no studies with objectives that aligned with the initial intended use of the PCOA as defined by the National Association of Boards of Pharmacy, which included tracking individual student performance throughout the curriculum, benchmarking programs against other programs, and evaluating whether a program was meeting their desired outcomes. Additionally, no consensus across the Academy was found as to the proper use of the PCOA, and a paucity of literature exists regarding how the PCOA informs schools and colleges about the effectiveness of their curriculum. There is a need for the Academy to establish a uniform application for the PCOA in pharmacy schools, assess the resources that programs need to administer this required assessment, and determine the utility of the PCOA to measure curricular effectiveness and/or student performance.

Making Diagnostic Instruction Explicit in US Pharmacy Education.

The profession of pharmacy and standards directing the education of student pharmacists are constantly evolving. The profession continues to emphasize patient-centered practice as a model for the future. The US health care system is faced with an impending shortage of primary care providers, which will affect the ability of patients to access the health care system. The pharmacy profession should position itself to contribute to meeting this need. The explicit instruction of differential diagnosis within Doctor of Pharmacy degree programs is a critical consideration in advancing pharmacy practice and potential contributions to the primary care gap.

Mechanism of Altered Metformin Distribution in Nonalcoholic Steatohepatitis.

Metformin is an antihyperglycemic drug that is widely prescribed for type 2 diabetes mellitus and is currently being investigated for the treatment of nonalcoholic steatohepatitis (NASH). NASH is known to alter hepatic membrane transporter expression and drug disposition similarly in humans and rodent models of NASH. Metformin is almost exclusively eliminated through the kidney primarily through active secretion mediated by Oct1, Oct2, and Mate1. The purpose of this study was to determine how NASH affects kidney transporter expression and metformin pharmacokinetics. A single oral dose of [(14)C]metformin was administered to C57BL/6J (wild type [WT]) and diabetic ob/ob mice fed either a control diet or a methionine- and choline-deficient (MCD) diet. Metformin plasma concentrations were slightly increased in the WT/MCD and ob/control groups, whereas plasma concentrations were 4.8-fold higher in ob/MCD mice compared with WT/control. The MCD diet significantly increased plasma half-life and mean residence time and correspondingly decreased oral clearance in both genotypes. These changes in disposition were caused by ob/ob- and MCD diet-specific decreases in the kidney mRNA expression of Oct2 and Mate1, whereas Oct1 mRNA expression was only decreased in ob/MCD mice. These results indicate that the diabetic ob/ob genotype and the MCD disease model alter kidney transporter expression and alter the pharmacokinetics of metformin, potentially increasing the risk of drug toxicity.