Insulin Requirements for Patients With COVID-19 Presenting With Diabetic Ketoacidosis.

Introduction Recent literature has shown that patients with COVID-19 and diabetic ketoacidosis may require more aggressive treatment than those with diabetic ketoacidosis alone. The primary objective of this study was to assess if intravenous regular human insulin infusion requirements in patients with diabetic ketoacidosis differed between patients with or without COVID-19. Methods This retrospective cohort study evaluated patients with diabetic ketoacidosis who received intravenous regular human insulin infusion during the COVID-19 pandemic. The primary outcome was the amount of intravenous regular human insulin infusion requirements needed during the diabetic ketoacidosis episode. Results Of the 77 patients that met inclusion criteria, 35 were positive for COVID-19 and 42 were negative. The primary outcome of total intravenous regular human insulin infusion requirements needed during the diabetic ketoacidosis episode was not statistically significant and resulted in 1.79±0.61 units/kg/day in the COVID-19 positive group and 1.81±0.6 units/kg/day in the negative group (p=1). Secondary outcomes that were statistically significant between groups were the amount of fluids received in the first 24 hours, potassium supplementation, phosphate supplementation, acute kidney injury, and hypokalemia. Conclusion There was no difference in intravenous regular human insulin infusion requirements in the setting of diabetic ketoacidosis (DKA) between COVID-19 positive and negative patients.

Optimization of antidote stocking, availability, and administration practices for a large multihospital organization.

PURPOSE: Inadequate hospital antidote inventory is a widely documented international issue due to high medication costs, lack of emphasis on antidote importance, variable international standards, hospital size, and drug availability. A large health system underwent process and policy implementation for antidote stocking, availability tracking, and administration strategies to ensure appropriate inventory and improve patient safety. SUMMARY: Process and policy implementation occurred over a 12-month period across the health system's 11 acute care hospitals with emergency department services. Opportunities for optimization were identified following data capture surrounding institution-specific antidote inventory and usage across the health system. Specifically, minimum par levels at each institution were determined from 2018 expert recommendations for both the central pharmacy and automated dispensing machines within the emergency department. These quantities ensured the availability of an antidote within a specific timeframe contingent on the acquisition acuity for at least one 100-kg patient. Entries for order sets, order statements, and smart pump drug libraries were modified or formulated to facilitate standardized practices and minimize safety errors before a system-wide electronic health record transition. CONCLUSION: It is prudent for all institutions, independent or within a health system, to identify areas of improvement for antidote inventory and management. Implementation of a similar process for antidote stocking, sharing, and delivery at other institutions is feasible and necessary to mitigate issues with drug acquisition and timely administration.

Real-world evaluation of the impact of two anti-SARS-CoV-2 monoclonal antibody regimens on COVID-19 hospitalizations in older adults.

Evidence from clinical trials suggest anti-SARS-CoV-2 monoclonal antibodies (mABs) may reduce coronavirus disease 2019 (COVID-19)-related hospitalizations. The purpose of this study was to assess the real-world impact of mAB administration on COVID-19 hospitalization among patients 65 years or older. This was a retrospective, propensity-matched cohort study that included patients aged 65 years and older who presented to the emergency department (ED) within 10 days of symptom onset of mild to moderate COVID-19 infection. Outcomes were compared between those who did and did not receive mAB therapy. The primary endpoint was the rate of hospitalization for COVID-19 within 30 days of index ED visit. A total of 137 patients receiving mABs were matched to 137 controls. Hospitalization occurred in 2.9% of mAB-treated patients compared to 14.6% of patients of the standard of care (SOC) arm (odds ratio: 0.20 [95% CI: 0.07-0.59]). There were zero intubations and zero deaths compared to 3 (2.2%) and 2 (1.5%) in the SOC group. Among the 223 patients receiving mAB in the overall cohort, adverse drug events occurred in 10 (4.5%). Treatment with mAB therapy for mild to moderate COVID-19 was associated with a substantially reduced risk of hospitalization among patients at least 65 years of age.

Improving the Flow: Optimization of Available Triage Standing Medication Orders in the Pediatric Emergency Department.

BACKGROUND: Emergency department (ED) overcrowding has led to longer waits for patients to be seen, treated, and released. This has been coupled with an increased number of patients who leave without ever being seen by an ED provider. Improving patient throughput and decreasing ED patient length of stay while continuing to provide high-quality care is of paramount importance. Optimization of available standing orders for fever, pain, and/or nausea and vomiting at the time of nurse triage may offer an opportunity to improve patient outcomes, decrease time to medication (TTM) administration for ill and injured patients, and decrease length of stay. PATIENTS AND METHODS: This was a retrospective cohort patient analysis for patients younger than 18 years of age presenting to the ED before (February 2019) and after (February 2020) an intensive campaign aimed at educating the triage nurses regarding the use of ED standing orders for acetaminophen, ibuprofen, and ondansetron. The investigators sought to evaluate percentage change in nurse triage-initiated (NTI) orders between the 2 time frames. Secondary outcomes evaluated TTM, documented adverse effects, percentage of inappropriate medication administrations, and correlate TTMs to ED discharge. RESULTS: The percentage of patients who received an NTI medication was 49% in 2019 and 58% in 2020 (P = 0.257). For NTI orders, TTM initiation decreased in the postintervention group from an average of 45 minutes down to 37.6 minutes. In the overall cohort, TTM administration in the NTI group was a mean of 41.2 minutes compared with 75.9 minutes in the provider-initiated group (P < 0.0001). Length of stay was the same for the NTI versus the provider-initiated group in overall cohort (134.4 vs 142.9, P = 0.4303). No adverse events were identified. CONCLUSIONS: Nurse-initiated medication administration at the time of triage offers an opportunity to get patients vital treatment more quickly. Medications administrated earlier in the pediatric ED encounter have a correlation to improved throughput and higher possibility of quicker discharge from the ED. Further research is needed to fully assess the impact of continuing education on improving utilization of triage standing orders and the impact on ED throughput.

Real-World Observational Review of Andexanet Alfa Prescribing and Utilization Outcomes at a Community Teaching Hospital.

OBJECTIVES: Andexanet alfa is the first approved antidote in the management of life-threatening bleeds in patients treated with Xa inhibitors. The ANNEXA-4 study was successful in reducing factor Xa levels during time of administration but lacked correlation to improved patient outcomes. Given its novel mechanism of action, U.S. boxed warning, cost of up to $58,000 per dose, and limited efficacy data compared with standard of care, hospitals are faced with a dilemma with its addition to formulary and process for ensuring optimized use. The objective of this study was to evaluate adherence to institution restriction criteria and the clinical outcomes of treatment for patients for whom andexanet alfa is requested. DESIGN: Retrospective cohort study of andexanet alfa requests within a 12-month time period. SETTING: A 600-bed community teaching hospital. PATIENTS: Patients whom pharmacists received request for dispensing andexanet alfa. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Quality outcomes reviewed compliance to restriction criteria. Clinical outcomes evaluated use of adjunctive blood products, ICU length of stay, hospital length of stay, and hospital mortality. Safety outcomes evaluated incidence of thrombotic events.Andexanet alfa was requested for 16 patients from November 2018 to November 2019. It was administered in nine patients, with compliance to restriction criteria of 66.6%, average ICU length of stay 5.6 days, hospital length of stay 8.6 days, hospital mortality in 44.4%, and thrombotic events in 33.3%. Orders were rejected in seven patients with compliance to restriction criteria of 100%, ICU length of stay 3.2 days, hospital length of stay 5.5 days, hospital mortality in 14%, and thrombotic events in 14%. CONCLUSIONS: A greater rate of adverse effects and mortality was identified with the use of andexanet alfa compared with clinical trials. This is potentially due to its use in a more severely ill patient population and lack of adherence to restriction criteria.

Impact of Expansion of PGY1 Pharmacy Residency Program From 2 to 4 Residents.

PURPOSE: To evaluate the benefits of postgraduate year 1 (PGY1) pharmacy residency program expansion on clinical outcomes, pharmacy services, educational outreach, costs, and preceptor time at a community teaching hospital. METHODS: During academic years 2014 to 2016, two PGY1 resident positions existed, expanding to four PGY1 resident positions during 2016 to 2018. Quantitative analyses comparing the aforementioned periods evaluated clinical interventions, adverse drug events prevented, community and hospital educational programs provided, departmental costs, and documented preceptor hours as a result of program growth. The outcomes were assessed using descriptive statistics. RESULTS: The mean number of documented clinical interventions completed by the resident classes with two residents was 2906 when compared to 5324 with four residents. The mean number of prevented adverse drug events was 56 during the years with two residents and 220 in the years with four residents. The number of community outreach programs increased from 2 to 18 per year. The number of resident lectures provided to allied health professionals increased from 11 to 16 sessions per year. The net economic impact associated with two residents in 2014 was +$4661 USD, while in 2017 the net impact was -$5262 USD. The mean preceptor hours spent per year related to residency activities with two residents was 1005 hours compared to 1109.5 hours with four residents. CONCLUSION: Through strategic modification, expansion of the PGY1 residency program led to increased documentation of clinical interventions, prevented adverse drug events, and educational programs provided with minimal change in preceptor burden.

Abrupt versus gradual cessation of steroids in patients with septic shock.

PURPOSE: To determine if a difference in hemodynamic stability would be identified in patients with abrupt withdrawal of steroids compared to patients who underwent a taper. MATERIAL AND METHODS: This retrospective cohort study identified patients who received vasopressors followed by IV hydrocortisone for treatment of septic shock from January 1, 2013 until January 1, 2015.The primary endpoint evaluated the percent of patients requiring vasopressor re-initiation during taper and 72 h following taper, or 72 h directly following abrupt withdrawal. Secondary endpoints evaluated include glycemic control, and ICU length of stay. RESULTS: A total of 87 patients were included for final analysis. Of the 87 patients, 7 out of 41 patients (17.1%) in the steroid taper group developed hemodynamic instability and required re-initiation of vasopressors compared to 1 out of 46 patients (2.2%) in the abrupt withdrawal group (p = 0.024). Patients in the taper group also had worse glycemic control (125.1 mg/dL abrupt vs. 150.8 taper; p < 0.001). There was no statistical difference found in the ICU length of stay (8.28 days abrupt vs.10.73 taper; p = 0.14). CONCLUSION: The abrupt withdrawal of steroids in patients with resolving septic shock did not impact hemodynamic stability and offers an opportunity to reduce medication burden and reduce adverse drug reactions.

Development of Antibiotic Stewardship Practices Targeting Urinary Tract Infections in a Hospital With Consultant-Based Infectious Disease Services.

PURPOSE: Ensuring proper use of antimicrobials through the development and implementation of stewardship programs translates to improved patient outcomes. This article will describe the development of an antibiotic stewardship program at a facility with consultant-based infectious disease services. METHODS: Program development involved a multifaceted approach, including identification of a physician stewardship champion, design of a retrospective analysis, development of a physician scoring card, and creation and auditing of a real-time reporting system targeting prospective de-escalation opportunities. A seven-month retrospective chart analysis was performed on patients from two medical telemetry units with a diagnosis-related code for urinary tract infection to identify current prescribing practices of antimicrobials. The primary endpoint assessed the percentage of patients with missed opportunities for de-escalation. Secondary endpoints evaluated the impact on costs and hospital length of stay, comparing patients who were appropriately treated with those with missed de-escalation opportunities. RESULTS: Seventy-five patients were evaluated, 30 (40%) of whom were identified as having had missed opportunities for de-escalation. The cost of antibiotics for patients who were de-escalated averaged approximately $22.18 per day, compared with $70.26 per day (P = 0.04) for those with missed de-escalation opportunities. Patients receiving appropriate therapy had an average hospital length of stay of 6.42 days compared with 8.13 days for the missed-opportunity group (P = 0.052). CONCLUSION: The development of stewardship services at a consultant-based hospital is possible through a systematic approach, ultimately resulting in the expansion of available personnel and promotion of collaborative efforts.

Systemic Thrombolysis for Pulmonary Embolism: A Review.

The authors review the evidence behind the use of thrombolytic therapy in patients with massive or submassive pulmonary embolism. Concurrent heparin therapy and the management of bleeding episodes are also discussed.

ABCB5-Targeted Chemoresistance Reversal Inhibits Merkel Cell Carcinoma Growth.

Merkel cell carcinoma (MCC) is a highly aggressive neuroendocrine skin cancer with profound but poorly understood resistance to chemotherapy, which poses a significant barrier to clinical MCC treatment. Here we show that ATP-binding cassette member B5 (ABCB5) confers resistance to standard-of-care MCC chemotherapeutic agents and provide proof-of-principle that ABCB5 blockade can inhibit human MCC tumor growth through sensitization to drug-induced cell cytotoxicity. ABCB5 expression was detected in both established MCC lines and clinical MCC specimens at levels significantly higher than those in normal skin. Carboplatin- and etoposide-resistant MCC cell lines exhibited increased expression of ABCB5, along with enhanced ABCB1 and ABCC3 transcript expression. ABCB5-expressing MCC cells in heterogeneous cancers preferentially survived treatment with carboplatin and etoposide in vitro and in human MCC xenograft-bearing mice in vivo. Moreover, patients with MCC also exhibited enhanced ABCB5 positivity after carboplatin- and etoposide-based chemotherapy, pointing to clinical significance of this chemoresistance mechanism. Importantly, ABCB5 blockade reversed MCC drug resistance and impaired tumor growth in xenotransplantation models in vivo. Our results establish ABCB5 as a chemoresistance mechanism in MCC and suggest utility of this molecular target for improved MCC therapy.