Virtual self-care simulations for third-year pharmacy skills laboratory courses in three institutions.

BACKGROUND AND PURPOSE: This study was designed to determine whether a virtual, self-care activity improved knowledge and confidence in third-year student pharmacists. EDUCATIONAL ACTIVITY AND SETTING: Third-year student pharmacists (n = 386) from three institutions participated in the virtual self-care simulation during their respective practice laboratory course. A pre- and post-assessment collected 10 knowledge and five confidence questions, self-reported on 0-100 scale, mapped to learning outcomes and pharmacy standards. Responses for participants who provided consent and had linked assessments were analyzed. Additionally, students participated in a perception assessment following the simulation with the post-assessment. Each knowledge question was scored as binary (correct/incorrect), presented as percentage, and significance identified with a McNemar's test. Total knowledge score and confidence changes were presented as means with standard deviations and significance with a paired t-test. Student perceptions were presented as frequencies and percentages. FINDINGS: Total knowledge assessment demonstrated a significant improvement (p < 0.001) for the entire cohort of 198 study participants. Upon additional analysis, a single institution led the cohort to significant increase, with variable improvement and significance for each individual question. Confidence improved for the entire cohort of students and at each institution individually. The students perceived the virtual self-care activity favorably. SUMMARY: The third-year student virtual self-care activity improved knowledge and confidence with varying significance between institutions. Future studies will focus on the impact of continued reinforcement of self-care activities on student growth in knowledge and confidence.

Implementation of genomic medicine for rare disease in a tertiary healthcare system: Mayo Clinic Program for Rare and Undiagnosed Diseases (PRaUD).

BACKGROUND: In the United States, rare disease (RD) is defined as a condition that affects fewer than 200,000 individuals. Collectively, RD affects an estimated 30 million Americans. A significant portion of RD has an underlying genetic cause; however, this may go undiagnosed. To better serve these patients, the Mayo Clinic Program for Rare and Undiagnosed Diseases (PRaUD) was created under the auspices of the Center for Individualized Medicine (CIM) aiming to integrate genomics into subspecialty practice including targeted genetic testing, research, and education. METHODS: Patients were identified by subspecialty healthcare providers from 11 clinical divisions/departments. Targeted multi-gene panels or custom exome/genome-based panels were utilized. To support the goals of PRaUD, a new clinical service model, the Genetic Testing and Counseling (GTAC) unit, was established to improve access and increase efficiency for genetic test facilitation. The GTAC unit includes genetic counselors, genetic counseling assistants, genetic nurses, and a medical geneticist. Patients receive abbreviated point-of-care genetic counseling and testing through a partnership with subspecialty providers. RESULTS: Implementation of PRaUD began in 2018 and GTAC unit launched in 2020 to support program expansion. Currently, 29 RD clinical indications are included in 11 specialty divisions/departments with over 142 referring providers. To date, 1152 patients have been evaluated with an overall solved or likely solved rate of 17.5% and as high as 66.7% depending on the phenotype. Noteworthy, 42.7% of the solved or likely solved patients underwent changes in medical management and outcome based on genetic test results. CONCLUSION: Implementation of PRaUD and GTAC have enabled subspecialty practices advance expertise in RD where genetic counselors have not historically been embedded in practice. Democratizing access to genetic testing and counseling can broaden the reach of patients with RD and increase the diagnostic yield of such indications leading to better medical management as well as expanding research opportunities.

CT cisternography to visualize epidermoid tumors for stereotactic radiosurgery treatment planning.

The visualization of intracranial epidermoid tumors is often limited by difficulties associated with distinguishing the tumor from the surrounding cerebrospinal fluid using traditional computed tomography (CT) or magnetic resonance imaging (MRI) modalities. This report describes our experience using CT cisternography to visualize intracranial epidermoid tumors in three illustrative cases. CT cisternography of the epidermoid tumor provides more clarity and precision compared to traditional neuroimaging modalities. We demonstrate the feasibility of using CT cisternography to produce high-resolution images with well-defined tumor margins that can be used effectively for precise SRS treatment planning.

Utilization of the Ballast Long Guiding Sheath for Neuroendovascular Procedures: Institutional Experience in 68 Cases.

Background: The rise of neurointerventional devices has created a demand for guide systems capable of navigating to the carotid artery consistently regardless of tortuosity. The shift toward large distal access catheters (DACs) and desire for greater trackability have inspired the creation of flexible, supportive, large-lumen long guiding sheaths. Recently, the Ballast long guiding sheath was introduced to provide stability and flexibility while navigating neurointerventional devices through tortuous intracranial anatomy. Objective: To report our experience using the Ballast long guiding sheath in a series of patients undergoing a variety of neuroendovascular procedures. Methods: We retrospectively identified all patients who underwent neuroendovascular treatment with a long guiding sheath were selected from a prospectively maintained endovascular database from January 2019 to November 2019. Baseline clinical characteristics and procedural details were collected. Results: A total of 68 patients were included, mean patient age 67.6 ± 13.6 years. Of the patients treated, 52.9% (36/68) presented with stenosis, 25% (17/68) with aneurysms, 13.2% (9/68) with stroke or emboli, 1.5% (1/68) with a tumor, 1.5% (1/68) with an arteriovenous fistula (AVF), and 4.4% (3/68) with a carotid web. Of the patients with stenosis, 20/36 (55.6%) were extracranial, and 16/36 (44.4%) were intracranial. The Ballast long guiding sheath was used to deliver treatment devices for stenting (37/68, 54.4%), flow diversion (12/68, 17.6%), mechanical thrombectomy (8/68, 11.8%), endovascular coiling (5/68, 7.4%), liquid embolization (3/68, 4.4%), balloon angioplasty (2/68, 2.9%), and balloon angioplasty with stenting (1/68, 1.5%). No Ballast-related complications or adverse events were encountered. Conclusions: We demonstrate the feasibility of the Ballast long guiding sheath to successfully deliver modern neurointerventional treatment devices through tortuous anatomy.

Visualization of flow diverter stent wall apposition during intracranial aneurysm treatment using a virtually diluted cone beam CT technique (Vessel ASSIST).

PURPOSE: Flow diverters (FD) have poor radiopacity, challenging visualization of deployment and vessel wall apposition with conventional neuroimaging modalities. We evaluated a novel cone beam computed tomography (CT) imaging technique that allows virtual dilution (VD) of contrast media to facilitate workflow and ensure accurate assessment of FD wall apposition. METHODS: We retrospectively evaluated all patients treated for intracranial aneurysms with FD at our institution between November 2018 and November 2019. Undiluted injected dual cone beam CT acquisitions performed post-stenting were displayed with VD software (GE Healthcare). The resulting images were compared with conventional two-dimensional (2D) digital subtraction angiography (DSA) images. Two neurointerventionalists (Reader 1 and Reader 2, (R1, R2)) independently assessed FD deployment and wall apposition. Confidence in the diagnosis, inter-reader agreement, and X-ray exposure were assessed. RESULTS: A total of 27 cases were reviewed. FD deployment and wall apposition scores were 4.2 ± 1.0 (R1) and 4.0 ± 1.1 (R2) for DSA and 3.7 ± 1.2 (R1) and 4.1 ± 1.0 (R2) for VD. Confidence in the diagnosis was improved with VD, with scores of 3.7 ± 0.7 (R1) and 4.0 ± 0.7 (R2) using DSA and 4.9 ± 0.2 (R1) and 4.9 ± 0.2 (R2) using VD (P < 0.001). Inter-reader agreement using 2D DSA was improved from moderate (0.49324) to good (0.7272) (P < 0.0001). There were no significant differences in inter-reader agreement in the deployment assessment (P = 0.68) or dose-area product (P = 0.54) between techniques. CONCLUSION: VD imaging with dual cone beam CT enables accurate assessment of FD wall apposition after deployment with greater confidence and improved inter-reader agreement versus conventional 2D DSA alone, with comparable X-ray exposure.

Angiotensin Receptor Blockers Effect on Serum Uric Acid-A Class Effect?

PURPOSE: To provide a comprehensive review to determine whether there is a class effect among angiotensin receptor blockers (ARBs) in relation to serum uric acid. SUMMARY: A literature search was conducted and 8 articles were identified for inclusion in this review. In the studies reviewed, candesartan and valsartan were shown to have either a neutral or negative effect on serum uric acid. Azilsartan was shown to have a negative impact on serum uric acid while eprosartan appeared to have no impact on serum uric acid levels. Irbesartan demonstrated either a neutral or positive effect on serum uric acid while losartan exhibited a positive effect. CONCLUSION: The available data indicate that the reduction of serum uric acid is not a class effect of ARBs. Of the available agents, only losartan has clear evidence of its ability to lower serum uric acid. For patients with high blood pressure and elevated serum uric acid, losartan should be considered as a first-line agent with irbesartan as an alternative when appropriate.

Utility of post-transplant anti-HLA antibody measurements in pediatric cardiac transplant recipients.

BACKGROUND: Studies have associated anti-HLA antibodies detected by panel-reactive antibody (PRA) with increased risk for rejection and transplant coronary artery disease (TCAD) in adults, but the role of PRAs in monitoring immunologic status after pediatric cardiac transplantation has not been described. METHODS: We reviewed post-transplant PRAs in 96 pediatric heart recipients. PRAs were performed concurrently with endomyocardial biopsy and if rejection was suspected. The presence of anti-HLA IgG antibodies was defined as >10% reactivity. Pre-transplant variables, including age, race, gender, pre-transplant PRAs and presence of a mechanical assist device, were correlated with post-transplant PRAs. Outcome variables included rejection history, TCAD incidence and survival. RESULTS: The mean age of patients was 9.0 +/- 6.8 years. A mean of 8.1 +/- 5.3 PRAs were measured over a follow-up period of 4.8 +/- 2.7 years. There was a mean of 0.55 +/- 0.71 rejection events per patient-year, and TCAD was detected in 19 (22%) patients. Nineteen patients (20%) had anti-HLA Class I antibodies and 37 (39%) had Class II antibodies detected after transplant. There was no association between Class I antibodies and survival, TCAD or rejection. Class II antibodies were associated with worse survival and a decreased time-free of TCAD. Class II antibodies were also associated with rejection at the time of measurement (sensitivity 17%, specificity 94%) and for the ensuing 3 months (sensitivity 12%, specificity 94%). CONCLUSIONS: Class II anti-HLA antibodies correlate with worse patient outcomes and rejection episodes after pediatric cardiac transplant. A low sensitivity precludes use as a sole diagnostic tool, but post-transplant PRAs may be an important adjunct in a multi-faceted algorithm to assess immunologic status.

Anti-human leukocyte antigen antibodies are associated with restenosis after percutaneous coronary intervention for cardiac allograft vasculopathy.

BACKGROUND: Percutaneous coronary intervention (PCI) to palliate cardiac allograft vasculopathy (CAV) has been associated with high restenosis rates, possibly related to increased inflammation associated with this disease. Whether markers of immunologic rejection are associated with restenosis in this population is unknown. The goal of the study was to determine the predictors of restenosis after PCI for CAV. METHODS: Records were reviewed retrospectively from a single, high-volume cardiac transplant center. Clinical, angiographic, and immunologic data were collected on all patients postorthotopic heart transplantation (OHT) that had subsequent PCI. Restenosis was defined as greater than 50% stenosis at the previous intervention site. RESULTS: PCI was successfully performed on 62 de novo lesions in 40 patients an average of 6.8+/-3.9 years after OHT. Angiographic follow-up data was available for 79%, with an average follow-up of 1.54+/-1.22 years. The 1-year restenosis rate was 49% (64% for balloon percutaneous transluminal coronary angioplasty and 33% for coronary stenting [P=0.09 for difference]). The frequency of immunoglobulin (Ig)G antibody to major histocompatibility complex (MHC) class I antigen was highly associated with risk of restenosis (hazard ratio [HR] 11.33, P=0.01). Greater stenosis severity and smaller target vessel diameter were also predictors of restenosis as in the nontransplant population. CONCLUSIONS: The findings suggest that in patients postPCI for CAV, humoral allo-immunity may contribute to restenosis and that IgG antibodies to MHC class I antigen may help predict the risk of restenosis after PCI in this population.

Interleukin-2 receptor blockade in cardiac transplantation: influence of HLA-DR locus incompatibility on treatment efficacy.

BACKGROUND: Because allograft rejection results from specific T-cell activation by donor human leukocyte antigens (HLA), new immunomodulatory therapies for organ-transplant recipients are used to selectively block T-cell activity without global immunosuppression. We investigated whether blockade of the high-affinity interleukin (IL)-2 receptor effectively prevented T-cell alloreactivity in cardiac transplantation. METHODS AND RESULTS: A study of a humanized monoclonal antibody against the high-affinity IL-2 receptor (daclizumab) was performed in 70 adult, cardiac-transplant recipients. Patients were stratified based on the degree of donor-recipient HLA-DR matches. Primary and secondary endpoints were incidence and frequency of high-grade allograft rejections, IL-2-dependent, T-cell outgrowth from biopsy sites as measured by lymphocyte growth assay, and production of anti-HLA antibodies. Treatment with daclizumab significantly prevented development of high-grade acute rejection in recipients with at least one donor HLA-DR locus match during the first 3 months posttransplantation; in this group 0 of 13 (0%) treated with daclizumab experienced at least one high-grade rejection versus 3 of 13 (23%) controls (P=0.05). In addition, 1 of 12 (9%) daclizumab-treated patients experienced one or more episodes of IL-2-dependent, T-cell outgrowth versus 5 of 12 (42%) patients in the untreated group (P=0.05). In contrast, daclizumab used at the same dose and schedule was not as effective in fully HLA-DR-mismatched recipients. After cessation of daclizumab, allograft rejection increased to levels seen in controls. CONCLUSIONS: IL-2-receptor blockade is effective for preventing alloreactivity and high-grade rejection in cardiac transplantation; however, its efficacy seemed to be influenced by the degree of donor-recipient, HLA-DR locus mismatching.