Development of a pharmacist-managed protocol for the transition from intravenous to subcutaneous insulin in critically ill adults.

PURPOSE: To evaluate the efficacy and safety of a pharmacist-managed protocol for transitioning critically ill patients from intravenous (IV) to subcutaneous insulin. METHODS: This single-center, retrospective, observational study included patients admitted to the medical or surgical/trauma intensive care unit who received a continuous infusion of IV insulin from January 2019 to April 2021. Patients were excluded if they were less than 18 years old, pregnant, or incarcerated or received IV insulin for the diagnosis of diabetic ketoacidosis, hyperglycemic hyperosmolar state, calcium channel blocker or ß-blocker overdose, or hypertriglyceridemia. The primary outcome was to evaluate the percentage of blood glucose (BG) concentrations within the target range of 70 to 150 mg/dL within 48 hours of the transition to subcutaneous insulin. Secondary outcomes included the percentage of BG concentrations within the goal range following transition at 0 to 12 hours and 12 to 24 hours, the incidence of hypo- and hyperglycemia, and the percentage of patients requiring dose adjustments after the initial transition. RESULTS: Pharmacists were able to achieve BG concentrations in the target range for 53% of transitions at 12 hours, 40% of transitions at 24 hours, and 47% of transitions at 48 hours. With respect to safety endpoints, the pharmacist-managed group had a low rate of hypoglycemia (1.0%) and no severe hypoglycemia. Hyperglycemia was reported for 28% of BG concentrations while severe hyperglycemia was reported for 27%. Pharmacists transitioned patients to an average of 63% of the 24-hour total daily dose of insulin as basal insulin. CONCLUSION: Pharmacists can effectively and safely transition critically ill patients from IV to subcutaneous insulin utilizing a standardized protocol.

Pharmacist Transition-of-Care Services Improve Patient Satisfaction and Decrease Hospital Readmissions.

BACKGROUND: Pharmacists ability to directly impact patient satisfaction through increases in the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) surveys utilizing transitions-of-care (TOC) services is unclear. METHODS: Retrospective analysis of TOC patients from 07/01/2018 to 03/31/2019 was conducted. Intervention (INV) patients received pharmacist medication reconciliation and education prior to discharge and post-discharge telephone follow-up. All other patients served as control group (CON). Primary outcome: Evaluate impact of TOC services on HCAHPS scores for "Communication about Medicines" and "Care Transitions." Secondary outcomes: 30-day readmissions, quantification of prevented potential safety events, assessment of discharge prescriptions sent to the academic medical center outpatient pharmacy (MOP) for TOC patients. RESULTS: Of 1,728 patients screened, 414 patients met inclusion criteria (INV = 414, CON = 1314). A significant improvement (14.7%; p = <0.0001) in overall medication-related HCAHPS results was seen when comparing pre- vs post-implementation of the TOC service. Statistically significant increases for individual questions "staff told you what the medicine was for" (14.2%; p = 0.018), "staff describe possible effects" (21.2%; p = 0.004), and "understood the purpose of taking medications" (11.4%; p = 0.035) were observed. A non-significant decrease in 30-day readmission rates for the groups was observed (CON 16.4%, INV 13.3%; p = 0.133); however, an unplanned subgroup analysis evaluating impact of discharge phone calls on 30-day readmission rates revealed a significant reduction of 17.3% to 12.4% (p = 0.007). One hundred forty-three medication safety event(s) were potentially prevented by the TOC pharmacist. Lastly, 562 prescriptions were captured at the MOP as a result of the TOC initiative. CONCLUSIONS: Pharmacy-based TOC models can improve patient satisfaction, prevent hospital readmissions, and generate revenue.

Conversion to an electronic missing medication request system at an academic medical center.

Missing medications can negatively contribute to the financial and operational workflows of pharmacy departments and add medication safety challenges. The missing medication request (MMR) system at the study institution converted to entirely electronic in June 2018 from a hybrid electronic system. This study evaluated 4-week periods pre- and post-conversion. The objective of this study was to evaluate the impact of conversion to an electronic MMR system on the quantity of requests received at an academic medical center. The average daily number of MMR's decreased from the pre-conversion group to the post-conversion group (1.77 (±0.16) vs 1.48 (±0.17), p < 0.001). During post-conversion, the median triage time was 8 min [3 min-19 min], pharmacists triaged 62.4% of requests, and 29.6% of requests were declined. Conversion to an electronic MMR system represents one solution to decreasing missing medications. Future studies are needed to evaluate the financial, operational, and medication safety impact of conversion.

Clinical and Economic Implications of Restrictions on Calcitonin Utilization in a Health System.

Background: Hypercalcemia is a relatively common problem that may require hospital admission based on severity. A treatment option for hypercalcemia is calcitonin given intramuscularly or subcutaneously. Purpose: In 2015, calcitonin was on our health system formulary, but due to a sharp rise in cost, restrictions were placed to ensure appropriate utilization. Intervention: These restrictions reserved calcitonin for patients with symptomatic hypercalcemia or severe hypercalcemia, which was defined as an ionized calcium of greater than 1.5 mmol/L and/or total/corrected calcium (Ca) of greater than 13 mg/dL. In addition to providing criteria for its use, calcitonin orders also had an automatic stop date of 24 hours to ensure no more than 2 doses were provided in a 24-hour period. After the initial 24 hours, a patient would have to be reviewed again before any further doses were ordered and administered. If the patient met criteria, an additional 2 doses could be given in the next 24 hours for a total maximum treatment of 4 doses over a 48-hour time frame. Results: An evaluation to assess health system-wide compliance of the usage of calcitonin restrictions regarding utilization, effectiveness, and cost was conducted. In the 2-month study time frame that was examined, there was a decrease in 66 vials of calcitonin that were dispensed. This represents a 43% reduction in usage and an estimated US $450,000 reduction in the total money spent for calcitonin annually. No notable differences in Ca reduction were identified between the groups. Conclusion: This evaluation revealed that putting health system-wide restrictions in use for a high-cost medication can have a major financial impact without compromising clinical efficacy.

Divergent Hemogen genes of teleosts and mammals share conserved roles in erythropoiesis: analysis using transgenic and mutant zebrafish.

Hemogen is a vertebrate transcription factor that performs important functions in erythropoiesis and testicular development and may contribute to neoplasia. Here we identify zebrafish Hemogen and show that it is considerably smaller (∼22 kDa) than its human ortholog (∼55 kDa), a striking difference that is explained by an underlying modular structure. We demonstrate that Hemogens are largely composed of 21-25 amino acid repeats, some of which may function as transactivation domains (TADs). Hemogen expression in embryonic and adult zebrafish is detected in hematopoietic, renal, neural and gonadal tissues. Using Tol2- and CRISPR/Cas9-generated transgenic zebrafish, we show that Hemogen expression is controlled by two Gata1-dependent regulatory sequences that act alone and together to control spatial and temporal expression during development. Partial depletion of Hemogen in embryos by morpholino knockdown reduces the number of erythrocytes in circulation. CRISPR/Cas9-generated zebrafish lines containing either a frameshift mutation or an in-frame deletion in a putative, C-terminal TAD display anemia and embryonic tail defects. This work expands our understanding of Hemogen and provides mutant zebrafish lines for future study of the mechanism of this important transcription factor.

Board of Pharmacy Practices Related to Medication Errors and Their Potential Impact on Patient Safety.

State boards of pharmacy are generally responsible for the governance of the practice of pharmacy. While the regulatory process and methods for accomplishing this task may vary by state, all boards of pharmacy must address medication errors committed by pharmacists. The National Association of Boards of Pharmacy (NABP) has recommended that state boards of pharmacy implement best practices and enforcement actions that are aimed to promote patient safety and reduce medication errors. The current study was designed to identify and compare current corrective action practices among boards of pharmacy in response to medication errors. An electronic survey regarding board policies and anticipated board actions in response to hypothetical medication error scenarios was sent to boards of pharmacy for completion. Approximately 45% of pharmacy boards responded. Survey responses demonstrated that corrective actions and consequences were levied against pharmacists inconsistently among state boards. Corrective action plans and process improvement components were lacking in a majority of state board of pharmacy practices. Medication safety education for pharmacists and for members on boards of pharmacy was insufficient in many states. Responses to hypothetical error scenarios indicated that most board actions are educational and punitive in nature, rather than focusing on systems improvement.

Markers of Islet Endothelial Dysfunction Occur in Male B6.BKS(D)-Leprdb/J Mice and May Contribute to Reduced Insulin Release.

Islet endothelial cells produce paracrine factors that support ß-cell function and growth. Endothelial dysfunction underlies diabetic microvascular complications; thus, we hypothesized that in diabetes, islet endothelial cells become dysfunctional, which may contribute to ß-cell secretory dysfunction. Islets/islet endothelial cells were isolated from diabetic B6.BKS(D)-Leprdb/J male (db/db) mice, treated with or without the glucose-lowering agent phlorizin, or from C57BL/6J mice fed a high-fat diet for 18 weeks and appropriate controls. Messenger RNA (mRNA) and/or the protein levels of the cell adhesion molecule E-selectin (Sele), proinflammatory cytokine interleukin-6 (Il6), vasoconstrictor endothelin-1 (Edn1), and endothelial nitric oxide synthase (Nos3; Nos3) were evaluated, along with advanced glycation end product immunoreactivity. Furthermore, an islet endothelial cell line (MS-1) was exposed to diabetic factors (glucose, palmitate, insulin, and tumor necrosis factor-α) for six days. Conditioned media were collected from these cells, incubated with isolated islets, and glucose-stimulated insulin secretion and insulin content were assessed. Islet endothelial cells from db/db mice exhibited increased Sele, Il6, and Edn1 mRNA levels, decreased Nos3 protein, and accumulation of advanced glycation end products. Phlorizin treatment significantly increased Nos3 protein levels but did not alter expression of the other markers. High-fat feeding in C57BL/6J mice resulted in increased islet Sele, Il6, and Edn1 but no change in Nos3. Exposure of islets to conditioned media from MS-1 cells cultured in diabetic conditions resulted in a 50% decrease in glucose-stimulated insulin secretion and 30% decrease in insulin content. These findings demonstrate that, in diabetes, islet endothelial cells show evidence of a dysfunctional phenotype, which may contribute to loss of ß-cell function.

Overall sulfation of heparan sulfate from pancreatic islet ß-TC3 cells increases maximal fibril formation but does not determine binding to the amyloidogenic peptide islet amyloid polypeptide.

Islet amyloid, a pathologic feature of type 2 diabetes, contains the islet ß-cell peptide islet amyloid polypeptide (IAPP) as its unique amyloidogenic component. Islet amyloid also contains heparan sulfate proteoglycans (HSPGs) that may contribute to amyloid formation by binding IAPP via their heparan sulfate (HS) chains. We hypothesized that ß-cells produce HS that bind IAPP via regions of highly sulfated disaccharides. Unexpectedly, HS from the ß-cell line ß-TC3 contained fewer regions of highly sulfated disaccharides compared with control normal murine mammary gland (NMuMG) cells. The proportion of HS that bound IAPP was similar in both cell lines (∼65%). The sulfation pattern of IAPP-bound versus non-bound HS from ß-TC3 cells was similar. In contrast, IAPP-bound HS from NMuMG cells contained frequent highly sulfated regions, whereas the non-bound material demonstrated fewer sulfated regions. Fibril formation from IAPP was stimulated equally by IAPP-bound ß-TC3 HS, non-bound ß-TC3 HS, and non-bound NMuMG HS but was stimulated to a greater extent by the highly sulfated IAPP-bound NMuMG HS. Desulfation of HS decreased the ability of both ß-TC3 and NMuMG HS to stimulate IAPP maximal fibril formation, but desulfated HS from both cell types still accelerated fibril formation relative to IAPP alone. In summary, neither binding to nor acceleration of fibril formation from the amyloidogenic peptide IAPP is dependent on overall sulfation in HS synthesized by ß-TC3 cells. This information will be important in determining approaches to reduce HS-IAPP interactions and ultimately prevent islet amyloid formation and its toxic effects in type 2 diabetes.