Implementation and Impact of Critical Care Pharmacist Addition to a Telecritical Care Network.

Critical care pharmacists when incorporated into the ICU team, have been shown to improve outcomes in critically ill patients by decreasing mortality, improving morbidity and reducing cost. As telehealth continues to evolve, the incorporation of a critical care pharmacist into a comprehensive telecritical care (TCC) service will allow increased comprehensive pharmacotherapeutic care for those in smaller, community or rural hospitals. OBJECTIVES: To describe the implementation of a TCC pharmacist into an established TCC network, classify interventions performed, and quantify cost avoidance generated through pharmacist interventions. DESIGN: Multicenter, observational cohort study and retrospective return on investment, performed between December 2019 and December 2021. SETTING AND PARTICIPANTS: Critically ill adult patients, admitted to an ICU located in any of our eight community hospitals (50 ICU beds) within a large, 25-hospital integrated healthcare system (563 ICU beds total) in the United States. MAIN OUTCOMES AND MEASURES: The TCC pharmacist service was implemented in 8-hour shifts, initially available 5 days per week, then expanded to 7 days per week. Critical care pharmacist interventions were categorized by clinical type established utilizing American Society of Health-System Pharmacists benchmarking standards and the latest cost avoidance data. RESULTS: During the 2-year analysis period, TCC pharmacists documented 2,838 interventions generating $1,664,254 of gross cost avoidance and a return on investment of 4.5:1. CONCLUSIONS AND RELEVANCE: It is feasible to implement a TCC pharmacist within an established TCC network. Our experience showed enhanced comprehensive care of critically ill patients located in community hospitals within a large, integrated healthcare system, demonstrated significant cost avoidance, and has led to other initiatives, including a collaborative clinical/operational partnership with Life Flight.

Variables associated with adequate INR reversal in warfarin treated patients receiving 4-factor prothrombin complex concentrate.

Dosing of 4-factor prothrombin complex concentrate (4FPCC) in warfarin treated patients generally utilizes international normalized ratio (INR) and patient weight. The recommended maximum dosing for all INR categories is capped at 100 kg weight. Whether this affects INR reversal is unknown. Furthermore, characteristics associated with adequate INR reversal need to be further elucidated. This was a multi-center, retrospective cohort study of 186 patients who received 4FPCC for INR reversal in the setting of warfarin-associated hemorrhage or need for emergent INR reversal. Utilizing multiple regression analysis, we evaluated INR reversal, achievement of hemostasis, and 28-day all-cause mortality. A target INR < 1.4 was achieved in 132 of 186 patients (71%). Factors significantly affecting the odds of achieving target INR were age in years (OR 1.03; 95% CI 1.01-1.06; P = 0.01), weight-based 4FPCC dose (units/kg) (OR 1.04; 95% CI 1.00-1.08; P = 0.03), and 4FPCC dosing normalized to INR (units/kg/INR) (OR 1.18; 95% CI 1.03-1.35; P = 0.02). Hemostasis was achieved in 109 of 148 bleeding patients (73.6%). Blood transfusions were associated with not achieving hemostasis (OR 0.44; 95% CI 0.21-0.93; P = 0.03). All-cause 28-day mortality was 21.5% and was associated with intracranial hemorrhage (OR 2.83; 95% CI 1.38-5.8; P = 0.01). Adequate INR reversal was associated with age, weight-based 4FPCC dose, and dosing normalized to INR (units/kg/INR). Future studies should evaluate the appropriateness of current INR targets for warfarin reversal and alternative 4FPCC dosing strategies such as utilizing a 4FPCC dosing ratio of units/kg/INR.

High-dose versus low-dose 4-factor prothrombin complex concentrate for factor Xa inhibitor reversal in intracranial hemorrhage.

BACKGROUND & PURPOSE: 4-factor prothrombin complex concentrate (4FPCC) is used off-label for factor Xa (FXa) inhibitor-associated intracranial hemorrhage (ICH). Guideline recommendations provide various 4FPCC dosing regimens for FXa inhibitor reversal in this setting. We evaluated 4FPCC weight-based dosing and outcomes in FXa inhibitor-associated ICH. METHODS: We conducted a multi-center, retrospective, cohort study of ICH patients between July 2017 and February 2020. Patients were greater than 18 years of age, received 4FPCC, and were taking apixaban, rivaroxaban, or edoxaban. Patients were separated into high- (≥35 units/kg) or low-dose (<35 units/kg) 4FPCC groups. The primary outcome was hemostasis achievement. Secondary outcomes included in-hospital mortality, intensive care unit and hospital length of stay, discharge disposition, and thrombotic events. Outcomes were evaluated with binary logistic regression. RESULTS: Of 390 patients identified, 89 were included with 74 and 15 in the high- vs low-dose groups, respectively. Mean (SD) age was 76.6 (±10.8) years. Most were taking a FXa inhibitor for atrial fibrillation (76.4%) and apixaban was the most common FXa inhibitor (65.2%). Hemostasis achievement was greater in the high- vs low-dose group (89.2% vs 46.7%; OR 11.2; 95% CI 2.4-52.6, P = 0.002). Thrombotic events were 8.2% and 6.7% in the high vs low-dose groups, respectively (OR 0.8; 95% CI 0.08-8.2, P = 0.87). No statistically significant differences were found in secondary outcomes. CONCLUSION: In patients with FXa inhibitor-associated ICH, high-dose 4FPCC was associated with increased odds of hemostasis achievement. There was no difference in thrombotic events.

Patterns and Appropriateness of Thrombophilia Testing in an Academic Medical Center.

BACKGROUND: Clinical guidelines recommend against routine use of thrombophilia testing in patients with acute thromboembolism. Thrombophilia testing rarely changes acute management of a thrombotic event. OBJECTIVE: To determine appropriateness of thrombophilia testing in a teaching hospital. DESIGN: Retrospective cohort study. SETTING: One academic medical center in Utah. PARTICIPANTS: All patients who received thrombophilia testing between July 1, 2014, and December 31, 2014. MAIN MEASUREMENTS: Proportion of thrombophilia tests occurring in situations associated with minimal clinical utility, defined as tests meeting at least 1 of the following criteria: discharged before results available; test type not recommended; testing in situations associated with decreased accuracy; duplicate testing; and testing following a provoked thrombotic event. RESULTS: Overall, 163 patients received a total of 1451 thrombophilia tests for stroke (50% of tests; 35% of patients), venous thromboembolism (21% of tests; 21% of patients), and pregnancy-related conditions (15% of tests; 25% of patients). Of the 39 different test types performed, the most common were cardiolipin IgG and IgM antibodies (9% each), lupus anticoagulant (9%), and ß2-glycoprotein 1 IgG and IgM antibodies (8% each). In total, 911 tests (63%) were performed in situations associated with minimal clinical utility, with 126 patients (77%) receiving at least one such test. Only 2 patients (1%) had clear documentation of being offered genetic consultation. CONCLUSIONS: Thrombophilia testing in this single-center study was often associated with minimal clinical utility. Strategies to improve testing practices (eg, hematology specialty consult prior to inpatient testing, improved order panels) might help minimize inappropriate testing and promote value-driven care.

Risk of Resistant Organisms and Clostridium difficile with Prolonged Systemic Antibiotic Prophylaxis for Central Nervous System Devices.

BACKGROUND: Prolonged systemic antibiotic prophylaxis for central nervous system (CNS) devices may be associated with increased risk of antimicrobial resistance. The primary objective of this study was to determine the impact of prolonged CNS device antibiotic prophylaxis on the growth of resistant microorganisms and Clostridium difficile. METHODS: This retrospective, observational, cohort study included patients admitted to intensive care units with traumatic brain injury or other neurocritical illness. Patients who received a CNS device and antibiotic prophylaxis for at least 72 h were compared to patients with similar neurologic injuries who did not receive a CNS device. RESULTS: Study (n = 116) and control (n = 557) patients had mean APACHE II scores of 17.7 ± 9.2 and 15.1 ± 10.6 (p = 0.004) with 53.4 and 24.6 % receiving craniotomies (p < 0.001), respectively. Mean CNS device duration was 9.9 days, and 73 % of patients received cefuroxime for prophylaxis. The study cohort had a higher absolute incidence of resistant organisms compared with the control cohort (15.5 vs 4.1 %; odds ratio 1.93, 95 % CI 0.93-4.03, p = 0.078), though the study was underpowered to show statistical significance in multivariate analysis. C. difficile incidence was similar between groups (2.6 vs 2.0 %; odds ratio 1.45, 95 % CI 0.35-6.12, p = 0.61). CONCLUSION: We found a higher incidence of resistant organisms in patients receiving prolonged antibiotic prophylaxis with a CNS device, but similar incidence of C. difficile compared to controls. Lack of data supporting prolonged antibiotic prophylaxis for CNS devices and the risk of nosocomial infections with resistant organisms encourage limiting prophylactic antibiotics to a short periprocedural course.

Interactions between the amyloid precursor protein C-terminal domain and G proteins mediate calcium dysregulation and amyloid beta toxicity in Alzheimer's disease.

Alzheimer's disease is characterized by neuropathological accumulations of amyloid beta(1-42) [A beta(1-42)], a cleavage product of the amyloid precursor protein (APP). Recent studies have highlighted the role of APP in A beta-mediated toxicity and have implicated the G-protein system; however, the exact mechanisms underlying this pathway are as yet undetermined. In this context, we sought to investigate the role of calcium upregulation following APP-dependent, A beta-mediated G-protein activation. Initial studies on the interaction between APP, A beta and Go proteins demonstrated that the interaction between APP, specifically its C-terminal -YENPTY- region, and Go was reduced in the presence of A beta. Cell death and calcium influx in A beta-treated cells were shown to be APP dependent and to involve G-protein activation because these effects were blocked by use of the G-protein inhibitor, pertussis toxin. Collectively, these results highlight a role for the G-protein system in APP-dependent, A beta-induced toxicity and calcium dysregulation. Analysis of the APP:Go interaction in human brain samples from Alzheimer's disease patients at different stages of the disease revealed a decrease in the interaction, correlating with disease progression. Moreover, the reduced interaction between APP and Go was shown to correlate with an increase in membrane A beta levels and G-protein activity, showing for first time that the APP:Go interaction is present in humans and is responsive to A beta load. The results presented support a role for APP in A beta-induced G-protein activation and suggest a mechanism by which basal APP binding to Go is reduced under pathological loads of A beta, liberating Go and activating the G-protein system, which may in turn result in downstream effects including calcium dysregulation. These results also suggest that specific antagonists of G-protein activity may have a therapeutic relevance in Alzheimer's disease.