Pharmacist Reported Protocols for QTc Monitoring of Psychiatric Medications.

Background Psychiatric medications, such as antipsychotics and antidepressants, are associated with QTc interval prolongation. There is currently no consensus best practice on how to mitigate this risk. This study aimed to collect and analyze information about methods used for QTc monitoring in patients taking psychiatric medications to better understand current practice. Methods An anonymous electronic survey was distributed on September 22, 2022, using a national psychiatric pharmacist organization email list. The survey closed on December 15, 2022. Descriptive statistics were used to analyze the multiple-choice questions. Qualitative analysis applying grounded theory for thematic analysis was performed for free response questions. Results A total of 48 initiated the survey. Of the respondents, 11.4% (5/44) reported that their institution had a formal protocol for monitoring QTc intervals in patients receiving psychiatric medications, while 32.4% (12/37) reported that their institution had an informal process. Out of those with a protocol or process, approximately half reported that it was drug-specific. Among the respondents, 88.6% (31/35) reported that there was a psychiatric clinical pharmacy specialist at their institution and 34.3% (12/35) reported that pharmacists could order an electrocardiogram (ECG). Major themes that emerged from the qualitative analysis included pharmacist-driven QTc monitoring, referring the patient to another provider for monitoring, and encountering significant barriers to monitoring. Conclusion A variety of methods are currently being employed to monitor QTc prolongation risk in patients taking psychiatric medications. Pharmacist authorization to order ECGs may be an opportunity to advance practice and improve care for this population. Further research is needed to more clearly understand best practices for QTc prolongation risk mitigation in patients receiving psychiatric medications.

Time-to-therapy discontinuation in patients newly diagnosed with schizophrenia initiated on long-acting injectable versus oral dopamine receptor blocking agents.

AIM: The purpose of this project is to assess the time-to-therapy discontinuation and hospital readmission rate among patients newly diagnosed with schizophrenia who are prescribed long-acting injectable versus oral dopamine receptor blocking agents. METHODS: A retrospective review of medical records was performed for adult patients admitted to an 80-bed inpatient behavioural health facility with a new diagnosis of schizophrenia. The primary outcome studied was time to therapy discontinuation within 1 year of discharge, while secondary outcomes assessed were time-to-therapy discontinuation within 90 days and readmission rate at 30-days, 6 months, and 1 year. Multivariate Cox proportional hazard and linear regression modelling were used for statistical analysis. RESULTS: A total of 425 patients were included in the analysis, with 66.4% (n = 282) discharged on oral and 33.6% (n = 143) on long-acting injectable dopamine receptor blocking agents. At 1 year post-discharge, the rates of discontinuation were 49.7% for those prescribed long-acting injectable and 55.7% for those prescribed oral formulations (adjusted hazard ratio = 0.54, p = .012). There was no statistically significant difference in readmission rate between the patients prescribed long-acting injectable and oral dopamine receptor blocking agents at any timepoint tested. CONCLUSIONS: The use of long-acting injectable dopamine receptor blocking agents was associated with longer time-to-discontinuation compared to oral agents when prescribed to patients newly diagnosed with schizophrenia in the inpatient setting. However, this was not associated with significant reductions in rehospitalization, calling into question the clinical impact. Future studies will seek to confirm these findings using a prospective study design.

Practical Approaches to Antipsychotic-Associated Corrected QT Interval Prolongation in Patients With Serious Mental Illness: A Review of Cases.

Background: There is no consensus for assessment and management of patients with serious mental illness (SMI) who are at risk for cardiac morbidity and mortality due to antipsychotic-associated QTc prolongation. Objective: The objective of this review was to assess methods for risk scoring, QT correction calculation, and clinical management in SMI patients with antipsychotic-associated QTc prolongation. Methods: A search was performed in PubMed for case reports that described QTc prolongation in adult patients with schizophrenia or bipolar disorder prescribed an antipsychotic. Reports published in North America between 2000 and 2020 were eligible. The Mayo, Tisdale, and RISQ-PATH scoring tools were applied to cases to categorize risk level. Results: Seventeen cases were included. Most patients were prescribed a second-generation antipsychotic for schizophrenia, with baseline and maximum QTc values of 429 milliseconds and 545 milliseconds, respectively. The Mayo scoring tool identified 17 (100%) cases as "high risk," Tisdale identified 9 (53%) cases as "moderate risk" and 7 (41%) cases as "low risk," while RISQ-PATH identified 9 (53%) cases as "not low risk" and 8 (47%) cases as "low risk." Three cases reported the QT correction formula utilized (18%). The most common intervention to address antipsychotic-associated QTc prolongation was switching to a different antipsychotic (35%). Approximately one third of patients experienced Torsades de Pointes. Conclusion: There is a lack of standardization for antipsychotic-associated QTc prolongation risk assessment and management in patients with SMI. This review provides real-world data representing actual clinical practice.

Tricyclic Antidepressant Overdose Manikin Simulation in Student Pharmacists.

Background: Pharmacists must be knowledgeable of medication use within the scope of both typical dosing and atypical dosing. In the United States, antidepressants are the fourth most common substance in overdose situations and are ranked first for serious exposures per year. Objective: The purpose of this study is to design, implement, and assess the efficacy of an antidepressant overdose simulation using a high-fidelity manikin. Methods: This was a single-center, prospective, observational, cross-sectional study of third-year student pharmacists in spring 2021. This study was determined to be exempt by the institutional review board. Students who did not participate in the manikin simulation or complete both the pre- and postsimulation surveys were excluded. Student pharmacists were expected to identify the type of overdose, identify probable offending agent, and evaluate the hemodynamic status. Primary objectives compared student pharmacist knowledge, confidence in recognizing overdose, and confidence in managing overdose pre- and post-antidepressant overdose manikin simulation. Results: Twenty-three students completed both surveys and participated in the simulation. The knowledge total score was 2.1 ± 1.3 in the presimulation and 2.9 ± 0.9 in the postsimulation (P < 0.001). The recognition confidence was 2.0 ± 1.3 in the presimulation and 3.7 ± 0.7 in the postsimulation (P < 0.001). The management confidence was 1.8 ± 1.0 in the presimulation and 3.5 ± 0.5 in the postsimulation (P < 0.001). Limitations in this study were small sample size, lack of rubric, and a case prompt. Conclusion: The outcomes were statistically significant postsimulation. Manikin simulations may have a larger impact on a pharmacy curriculum.

Attitudes and perceptions about the use of long-acting injectable antipsychotics among behavioral health practitioners.

Introduction: Long-acting injectable antipsychotics (LAI-As) are important tools for the treatment of schizophrenia, yet they appear to be underutilized. This study will assess practitioner perceptions of LAI-As to elucidate reasons for underuse and uncover new avenues to increase appropriate use. Methods: An anonymous electronic survey was developed and actively distributed to behavioral health care practitioners (MD, DO, PA, NP, PharmD, RN, LCSW). Independent t testing and linear regression analysis was used to assess for interactions between survey responses and individual factors. Results: A total of 146 survey responses were collected from September 3, 2020 to March 17, 2021. On average, participants thought that LAI-As were slightly underutilized in practice. The mean estimated patient acceptance rate for LAI-A therapy was 38.6% ± 29.5% (range = 0%-100%). Participants who were <40 years of age and those with a psychiatric pharmacist at their practice site had significantly higher estimated acceptance rates. The highest-rated barriers to LAI-A use were related to negative patient attitudes, lack of patient education, and access issues (eg, transportation, cost). Respondent characteristics including age, gender identity, geographic location, practice setting, and the presence of a psychiatric pharmacist significantly influenced the perceived impact of these barriers. Discussion: Behavioral health practitioners generally believed that LAI-As were underused, and only one-third of their patients would be accepting of the therapy. Several barriers were perceived as frequently impacting LAI-A use, but these were reduced by the presence of a psychiatric pharmacist. Understanding practitioner perceptions can assist with increasing the use of LAI-As.

Mental and physical health among students at a private university that held in-person classes during the COVID-19 pandemic.

OBJECTIVE: The COVID-19 pandemic is expected to have serious negative consequences on mental and physical health, which may disproportionally affect young adults. The aim of this study was to understand short-term impacts on a population of students at a college that held in-person classes during the pandemic. PARTICIPANTS: This study was conducted at a moderately-sized private university in the southeastern United States where approximately 75% of students were enrolled in undergraduate degree programs and 25% in graduate degree programs. METHODS: A survey was created to assess anxiety and depression symptoms, psychotherapeutic medication use, healthy living, and coping skills. Links to the electronic form were distributed to students via email in Spring 2020 and Fall 2020. Participation was completely voluntary and responses were collected anonymously. RESULTS: The rate of anxiety symptoms in the study cohort was higher than the national average (31%) and increased between Spring 2020 (39%) and Fall 2020 (50%). Rates of psychotherapeutic medication use also rose, with benzodiazepine use increasing from 6% to 11% and antidepressant use increasing from 16% to 20%. Compared to the national average, fewer students in the study cohort rated their overall health as "good" or better (72-76% vs. 82%). Physical exercise, nutrition, and alcohol use worsened between Spring and Fall 2020. Problem-focused engagement was associated with significantly fewer anxiety and depression symptoms. Demographic factors such as gender, race, and sexual orientation interacted with several outcomes studied. CONCLUSIONS: Students at a private university that held in-person classes during the COVID-19 pandemic reported high rates of anxiety that increased between Spring and Fall 2020. Self-reported physical health was below average in Spring 2020 but improved in Fall 2020. Appropriate identification and management of the effects of pandemic-related stressors is critical during this uncertain time.Supplemental data for this article can be accessed online at https://doi.org/10.1080/07448481.2022.2052074 .

Shifting from SOAP Notes to Consult Notes for Clinical Documentation by Pharmacy Students.

Objective. Clinical documentation is an important element of patient care that pharmacy students traditionally learn through subjective-objective-assessment-plan (SOAP) notes. In clinical practice, pharmacists often document more succinctly, both in length and time, using formats such as consult notes. The objective of this study was to assess consult note assignments for third-year pharmacy (P3) students.Methods. Consult note assignments were implemented in a P3 skills laboratory course by converting SOAP notes to consult notes. The series began with an introduction and a practice consult note. Four graded notes were then completed throughout the semester, whereby the time allotted for writing decreased throughout the semester. To assess the series, grades and estimated time to completion were collected for each graded note. A survey given before and after the course assessed student self-confidence in overall documentation, specific elements of consult notes, and concerns related to writing. Friedman tests were used to compare grades and times. Wilcoxon signed rank tests were used to compare self-assessments.Results. The median grades on the four consult notes were 92%, 88%, 80%, and 90%. Median times for completing each note were 75 minutes, 120 minutes, 60 minutes, and 60 minutes. Students' self-confidence in writing consult notes significantly increased, as did five of the six individual elements.Conclusion. The consult note assignments allowed students to practice documenting patient care in a succinct format with consideration for time efficiency. Further work should evaluate best pedagogies for teaching documentation skills and assess the impact on performance during advanced pharmacy practice experiences.

Characteristics of Inpatients Prescribed Dopamine Receptor Blocking Agents.

Dopamine receptor blocking agents (DRBAs, also known as antipsychotics) are frequently used in hospitalized patients. These medications carry a significant side effect burden and should be used judiciously. This purpose of this study is to examine patient, disease, and medication characteristics associated with the use of DRBAs in the inpatient setting to better understand current prescribing patterns and opportunities for optimization. A retrospective analysis was performed of 17,224 patients with at least one inpatient DRBA order placed between 1/1/2018-12/31/2019. The study population at this community hospital network in the United States contained those with (71.0%) and without (29.0%) psychiatric diagnoses, and the mean number of DRBA medications for each patient was 2.4 +/- 1.1. The characteristics of single, male, government-sponsored health insurance, movement disorder, DRBA adverse effects, and medication non-adherence were associated with significantly greater mean total DRBA medications prescribed. Medication non-adherence and prescription of a long-acting injectable (LAI) DRBA were greater in single and male patients, while suicidality was more likely in those with a movement disorder or DRBA adverse effect. Specific agents were also significantly associated with cardiovascular disease and metabolic disorder diagnoses. Based on the findings of this study, several patient, disease, and medication factors are related to the use of DRBAs in the hospital setting. It is important to further explore these associations in order to determine the appropriateness of DRBA prescribing and identify areas for improvement.

Adherence and persistence to long-acting injectable dopamine receptor blocking agent therapy in the United States: A systematic review and meta-analysis of cohort studies.

The purpose of this systematic review and meta-analysis was to assess adherence and persistence to long-acting injectable dopamine receptor blocking agents (LAI DRBAs) in published observational cohort studies conducted in the United States. Adherence rate (proportion of days covered ≥80%) and persistence rate (no gap in therapy ≥60 days) to LAI DRBAs were examined in 26 articles for qualitative review and 8 articles for quantitative review. There was significant variability in adherence and persistence rates to LAI DRBAs in the reported observational cohort studies. The mean adherence and persistence rates to LAI DRBAs in the included studies were 36% (8-66%) and 56% (32-80%), respectively. The use of LAI DRBAs showed cumulative benefit of achieving adherence 1.40 times higher compared to oral agents. The persistence rate was measured by number of patients having no more than 60 days gap in therapy at follow-up, and the cumulative benefit of being persistently on the therapy was 1.65 times higher among the LAI agents-exposed group compared to the oral agents-exposed group. The use of LAI DRBAs confers benefit in adherence and persistence compared to oral DRBA formulations.

Communicating definitive uncertainty: Teaching pharmacy students to say "I don't know".

BACKGROUND AND PURPOSE: Communicating uncertainty is an art requiring practice. The purpose of this study was to compare pedagogies for the instruction of pharmacy students in communicating definitive uncertainty. EDUCATIONAL ACTIVITY AND SETTING: A case scenario featuring a busy physician asking a question without a definitive answer was directed to the pharmacy student using two pedagogies: (1) in-person standardized client and (2) virtual written case. Students provided self-assessments of their confidence in communicating uncertainty after completing the case utilizing a survey containing both rating scale questions and open-ended questions. Self-confidence within-group differences were compared using Wilcoxon signed-rank tests and between-group differences were compared using Mann-Whitney U tests. Responses to open-ended questions were descriptively analyzed for themes using qualitative assessment methods. FINDINGS: Both the in-person standardized client (70 to 81, P ≤ .001) and the virtual written case (74 to 85, P ≤ .001) significantly increased students' self-rated confidence to verbalize "I don't know" to a healthcare provider. No significant differences were observed between the pedagogies. However, students who participated in the virtual written case mentioned a desire for "additional practice opportunities" more frequently than students who participated in the in-person standardized client. SUMMARY: In-person standardized client and virtual written case are effective methods for increasing pharmacy student comfort with communicating definitive uncertainty. Further research is needed to instruct pharmacists in uncertainty communication.

Assessing Psychiatric Comorbidity and Pharmacologic Treatment Patterns Among Patients With Neurofibromatosis Type 1.

Background and objective Neurofibromatosis 1 (NF1) is a genetic disorder that is accompanied by psychiatric comorbidities such as depression, anxiety, and attention-deficit hyperactivity disorder (ADHD) in more than half of the patients. However, there are limited data describing optimal treatment strategies for these conditions. This study aimed to address that gap in understanding and explore the neurobiological basis of psychiatric comorbidities in NF1. Materials and methods A retrospective cohort study was conducted among NF1 patients with a comorbid diagnosis of depression, anxiety, and/or ADHD. These disease states were chosen based on their relatively high reported prevalence in NF1 and shared pathophysiological mechanisms via monoaminergic dysfunction. Information regarding demographics, psychotherapeutic medication use, and clinical outcomes was gathered from electronic medical records. Relationships between patient- and medication-related factors and outcome measures were assessed using statistical analysis. Results The study population (n = 82) consisted of NF1 patients with a comorbid diagnosis of depression (76.8%), anxiety (53.7%), and/or ADHD (23.2%). The use of second-generation antipsychotic agent augmentation therapy or hydroxyzine monotherapy was associated with significantly more behavioral health (BH)-related emergency department (ED) visits, admissions, and inpatient days in the study population. Conversely, the use of bupropion augmentation therapy, buspirone augmentation therapy, and stimulants was associated with improved clinical outcomes, though these results were not statistically significant. Conclusions Based on our findings in this real-world study setting, patients with NF1 and psychiatric comorbidities appear to experience significant benefits from medications that enhance dopaminergic neurotransmission (e.g., bupropion, stimulants) when compared to drugs that oppose it (e.g., second-generation antipsychotics).

Nucleosomes inhibit target cleavage by CRISPR-Cas9 in vivo.

Genome editing with CRISPR-Cas nucleases has been applied successfully to a wide range of cells and organisms. There is, however, considerable variation in the efficiency of cleavage and outcomes at different genomic targets, even within the same cell type. Some of this variability is likely due to the inherent quality of the interaction between the guide RNA and the target sequence, but some may also reflect the relative accessibility of the target. We investigated the influence of chromatin structure, particularly the presence or absence of nucleosomes, on cleavage by the Streptococcus pyogenes Cas9 protein. At multiple target sequences in two promoters in the yeast genome, we find that Cas9 cleavage is strongly inhibited when the DNA target is within a nucleosome. This inhibition is relieved when nucleosomes are depleted. Remarkably, the same is not true of zinc-finger nucleases (ZFNs), which cleave equally well at nucleosome-occupied and nucleosome-depleted sites. These results have implications for the choice of specific targets for genome editing, both in research and in clinical and other practical applications.

Production of sialylated O-linked glycans in Pichia pastoris.

The methylotrophic yeast, Pichia pastoris, is an important organism used for the production of therapeutic proteins. Previously, we have reported the glycoengineering of this organism to produce human-like N-linked glycans but up to now no one has addressed engineering the O-linked glycosylation pathway. Typically, O-linked glycans produced by wild-type P. pastoris are linear chains of four to five α-linked mannose residues, which may be capped with ß- or phospho-mannose. Previous genetic engineering of the N-linked glycosylation pathway of P. pastoris has eliminated both of these two latter modifications, resulting in O-linked glycans which are linear α-linked mannose structures. Here, we describe a method for the co-expression of an α-1,2-mannosidase, which reduces these glycans to primarily a single O-linked mannose residue. In doing so, we have reduced the potential of these glycans to interact with carbohydrate-binding proteins, such as dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin. Furthermore, the introduction of the enzyme protein-O-linked-mannose ß-1,2-N-acetylglucosaminyltransferase 1, resulted in the capping of the single O-linked mannose residues with N-acetylglucosamine. Subsequently, this glycoform was extended into human-like sialylated glycans, similar in structure to α-dystroglycan-type glycoforms. As such, this represents the first example of sialylated O-linked glycans being produced in yeast and extends the utility of the P. pastoris production platform beyond N-linked glycosylated biotherapeutics to include molecules possessing O-linked glycans.

Case report: T-cell responses during clearance of Andes virus from blood cells 2 months after severe hantavirus cardiopulmonary syndrome.

Hantavirus Cardiopulmonary Syndrome (HCPS) due to Andes virus (ANDV) is endemic in Chile and Argentina and currently demonstrates a case-fatality rate of 37% in humans. By contrast to the chronically infected rodents, it is believed that ANDV in humans is cleared during the acute phase. Moreover, to date, both magnitude and quality of human T-cell responses during ANDV infection and clearance are unknown. Using IFN-gamma and granzyme B ELISPOT assays as well as flow cytometry, we prospectively studied the ANDV-specific T-cell responses in a 56-year-old convalescing survivor of severe HCPS, whose blood cells remained PCR-positive for ANDV-RNA until day 53 after hospital admission, that is, 67 days after infection and 42 days after discharge. PCR-negativity was closely related to the increase and function of (Gn(46-60))-specific IFN-gamma(+) granzyme B(+) CD8(+) T-cells, but not to neutralizing antibody titers. Concurrently, the phenotype of CD45RA(+)CCR7(-) Gn(46-60)-specific T-cells shifted from a CD28(-)CD27(+) "intermediate" to a CD28(-) CD27(-) "late" effector memory beyond day 53 after hospital admission. This is the first report that shows that ANDV can persist in the human hosts for more than 2 months. Moreover, the kinetics of T-cell responses during ANDV clearance may indicate a major role of T-cells for clearance of ANDV and human immunity to this pathogen.