Evaluation and optimization of medication related fall risk at a community hospital

Background: Falls occur commonly in older adults at a rate of 3-5 per 1000 beds in healthcare settings. They can results in increased length of stay, morbidity and mortality, and healthcare costs. Some risk factors include older age, environmental hazards and medications. Currently at BHM, patient’s risk for falling is assessed based on Morse Fall Scale (MFS), which does include drugs as part of its assessment. The purpose of this project is to integrate medication risk evaluation into our current fall assessment. Methodology: single-centered, retrospective, IRB-reviewed quality improvement project at BHM. We included patients over age 18 who fell with at least a minor injury (F2 level) in 2019. Our primary outcome was to determine prevalence of common high-fall-risk medications administered in patients who fell and our secondary outcome was to identify pharmacy-led interventions to decrease fall risk. Since MFS does not include medications as part of its score, we then evaluated each patient using a medication scoring system with point value of 1-3 for high-fall-risk medications (point value of 3 is assigned to high-fall-risk medications and point value of 1 is assigned to low fall risk medications). Any patient with a cumulative score of higher than 6 is recognized to be at high fall risk. Results: Primary outcome showed that cardiac agents, followed by opioids, and by benzodiazepines/sleep aids were the highest administered medications in our patients who fell. Based on those findings, we identified 29 opportunities where patient could have received lower doses and/or have had medication scheduling changes in order to reduce fall risk. We are proposing automatic dose adjustments similar to hydromorphone and zolpidem/temazepam protocols where pharmacists can reduce starting doses to lowest dose possible for drug naïve patients. In addition, we are proposing to have medication scoring system to be implemented into our software so pharmacists are notified if a patient is high risk for falls based on MFS score and medication score system. Conclusion: Pharmacists can play a huge role in reducing falls in inpatient settings. Based on our findings, some opportunities where pharmacists can intervene to reduce risk of falling include scheduling and automatic dose reductions with medications such as cardiac agents, opioids, and benzodiazepine/sleep aids

Evaluation of Four-Factor Prothrombin Complex Concentrate Dosing Strategies for the Reversal of Bleeding Associated with Apixaban or Rivaroxaban

In clinical practice, 4F-PCC is commonly used off-label as a non-specific reversal agent for factor Xa inhibitors apixaban and rivaroxaban. While the hemostatic effectiveness of 4F-PCC in patients taking apixaban and rivaroxaban has been studied in the literature, the optimal dose remains unclear. This was a multicenter, retrospective observational study designed to evaluate the hemostatic effectiveness and safety of 4F-PCC dosed at 2000 units, 35 units/kg, and 50 units/kg for the reversal of bleeding associated with apixaban or rivaroxaban. The primary outcome was hemostatic effectiveness as defined by the Internal Society of Thrombosis and Hemostasis and secondary outcomes were rates of all-cause in-hospital mortality and thrombosis at 30 days or discharge. Out of 278 patients who received 4F-PCC for reversal of bleeding associated with apixaban or rivaroxaban, 72 patients were included in the final analysis. The 2000-unit, 35 unit/kg, and 50 unit/kg dosing strategies were used in 12, 36, and 24 patients, respectively. Hemostatic effectiveness was achieved in 86%, 67%, and 70% of intracerebral hemorrhages (p = 0.762) and 60%, 71%, 86% of gastrointestinal hemorrhages (p = 0.422). Neither dosing strategy was associated with a statistically significantly higher rate of hemostatic effectiveness nor lower rates of all-cause mortality or thrombosis

Evaluation of clinical outcomes of 4-factor prothrombin complex concentrate versus andexanet alfa in the treatment of intracerebral hemorrhage

Purpose: Oral anticoagulants account for up to 20% of intracerebral hemorrhages (ICH) with one-year mortality estimated as high as 54%. Several studies have examined the use of 4-Factor prothrombin complex concentrate (4F-PCC) and andexanet alfa in the treatment of factor Xa associated ICH. High cost burden, lack of clinical outcomes, and risk of thromboembolic events continues to be a major dilemma behind product selection at many healthcare systems. The purpose of this project is to compare clinical outcomes between 4F-PCC and andexanet alfa in the management of patients with ICH secondary to apixaban and rivaroxaban at Baptist Hospital of Miami (BHM). Methodology: This single-center, performance improvement project was a retrospective chart review conducted for all patients admitted to BHM between August 1, 2018 and March 30, 2020. Patients were included if they received either 4F-PCC or andexanet alfa for the management of ICH induced by apixaban and rivaroxaban. The primary outcome of this project compared bleeding expansion at 24 and 48 hours among these two groups as defined by a brain computed tomography (CT) scan. Secondary outcomes included dose of reversal agent used, time to reversal agent administration in relation to the last direct oral anticoagulant (DOAC) dose, thromboembolic events within 30 days, hospital length of stay, mortality rate, and discharge status. Nominal data was presented as means and percentages. Baseline demographics and characteristics as well as primary and secondary outcomes were compared using the Fisher Exact test and Student’s T-test with p-values less than 0.05 considered statistically significant. Results: Overall, 62 patients were screened for inclusion and exclusion criteria. Of these, 19 patients were included and evaluated for primary and secondary outcomes. Eligible patients were divided into group I (andexanet alfa, n=7) and group II (4F-PCC, n=12). Several baseline demographics and patient characteristics were noted to be similar between these two groups, but not statistically significant. In reference to the primary outcome, patients in group I had 0% expansion of bleeds whereas group II patients had a 30% expansion of bleed, all non-surgical SDH (p=0.52). The average dose of 4F-PCC was 30 units/kg while 86% of the patients received low dose andexanet alfa. Administration of andexanet alfa and 4F-PCC in relation to the last DOAC dose was an average of 13 hours for both groups (p=0.91). The average hospital length of stay was 13 days for both groups (p=0.98). The incidence of thromboembolic events was noted to be 25% in group I while no thromboembolic events were noted in group II (p=0.26). Overall, there was a 14% mortality rate in group I versus 25% in group II (p=0.50). Conclusion: This study demonstrates clinical significant results relating to the efficacy and safety concerns of andexanet alfa and 4F-PCC in the management of ICH. As the results suggested, andexanet alfa treated patients had 0% expansion of bleed at 24 and 48 hours versus 30% in 4F-PCC treated patients (p=0.52), all non-surgical SDH. Moreover, the percent decrease in volume for the bleeding expansion was greater for andexanet alfa in the ICH arm, (52% vs 19%). Lastly, andexanet alfa treated patients had 0% thromboembolic rates versus 25% in 4F-PCC treated patients (p=0.26) with an overall mortality rate of 14% versus 25% respectively (p=0.50)

Deep Sequencing of RNA from Blood and Oral Swab Samples Reveals the Presence of Nucleic Acid from a Number of Pathogens in Patients with Acute Ebola Virus Disease and Is Consistent with Bacterial Translocation across the Gut.

In this study, samples from the 2013-2016 West African Ebola virus outbreak from patients in Guinea with Ebola virus disease (EVD) were analyzed to discover and classify what other pathogens were present. Throat swabs were taken from deceased EVD patients, and peripheral blood samples were analyzed that had been taken from patients when they presented at the treatment center with acute illness. High-throughput RNA sequencing (RNA-seq) and bioinformatics were used to identify the potential microorganisms. This approach confirmed Ebola virus (EBOV) in all samples from patients diagnosed as acute positive for the virus by quantitative reverse transcription-PCR in deployed field laboratories. Nucleic acid mapping to Plasmodium was also used on the patient samples, confirming results obtained with an antigen-based rapid diagnostic test (RDT) conducted in the field laboratories. The data suggested that a high Plasmodium load, as determined by sequence read depth, was associated with mortality and influenced the host response, whereas a lower parasite load did not appear to affect outcome. The identifications of selected bacteria from throat swabs via RNA-seq were confirmed by culture. The data indicated that the potential pathogens identified in the blood samples were associated with translocation from the gut, suggesting the presence of bacteremia, which transcriptome data suggested may induce or aggravate the acute-phase response observed during EVD. Transcripts mapping to different viruses were also identified, including those indicative of lytic infections. The development of high-resolution analysis of samples from patients with EVD will help inform care pathways and the most appropriate general antimicrobial therapy to be used in a resource-poor setting. IMPORTANCE Our results highlight the identification of an array of pathogens in the blood of patients with Ebola virus disease (EVD). This has not been done before, and the data have important implications for the treatment of patients with EVD, particularly considering antibiotic stewardship. We show that EVD patients who were also infected with Plasmodium, particularly at higher loads, had more adverse outcomes than patients with lower levels of Plasmodium. However, the presence of Plasmodium did not influence the innate immune response, and it is likely that the presence of EBOV dominated this response. Several viruses other than EBOV were identified, and bacteria associated with sepsis were also identified. These findings were indicative of bacterial translocation across the gut during the acute phase of EVD

Observation of a Coherence Length Effect in Exclusive Rho^0 Electroproduction

Exclusive incoherent electroproduction of the rho^0(770) meson from 1H, 2H, 3He, and 14N targets has been studied by the HERMES experiment at squared four-momentum transfer Q**2>0.4 GeV**2 and positron energy loss nu from 9 to 20 GeV. The ratio of the 14N to 1H cross sections per nucleon, known as the nuclear transparency, was found to decrease with increasing coherence length of quark-antiquark fluctuations of the virtual photon. The data provide clear evidence of the interaction of the quark- antiquark fluctuations with the nuclear medium.Comment: RevTeX, 5 pages, 3 figure

Stromal Interferon-γ Signaling and Cross-Presentation Are Required to Eliminate Antigen-Loss Variants of B Cell Lymphomas in Mice

To study mechanisms of T cell-mediated rejection of B cell lymphomas, we developed a murine lymphoma model wherein three potential rejection antigens, human c-MYC, chicken ovalbumin (OVA), and GFP are expressed. After transfer into wild-type mice 60–70% of systemically growing lymphomas expressing all three antigens were rejected; lymphomas expressing only human c-MYC protein were not rejected. OVA expressing lymphomas were infiltrated by T cells, showed MHC class I and II upregulation, and lost antigen expression, indicating immune escape. In contrast to wild-type recipients, 80–100% of STAT1-, IFN-γ-, or IFN-γ receptor-deficient recipients died of lymphoma, indicating that host IFN-γ signaling is critical for rejection. Lymphomas arising in IFN-γ- and IFN-γ-receptor-deficient mice had invariably lost antigen expression, suggesting that poor overall survival of these recipients was due to inefficient elimination of antigen-negative lymphoma variants. Antigen-dependent eradication of lymphoma cells in wild-type animals was dependent on cross-presentation of antigen by cells of the tumor stroma. These findings provide first evidence for an important role of the tumor stroma in T cell-mediated control of hematologic neoplasias and highlight the importance of incorporating stroma-targeting strategies into future immunotherapeutic approaches

Implementation of a conversion from intravenous alteplase to tenecteplase for treatment of acute ischemic stroke

Background/Purpose: In acute ischemic stroke patients meeting established criteria, thrombolytics may aid in the reperfusion of ischemic brain regions leading to improvement or resolution of neurological deficits. Alteplase is the only FDA approved thrombolytic for acute ischemic stroke. Recent evidence suggests tenecteplase is as safe and efficacious as alteplase, while providing a more favorable pharmacokinetic profile. The purpose of this project is to conduct a review of alteplase compared to tenecteplase for treatment of acute ischemic stroke, following a formulary conversion in the thrombolytic of choice across a large health system. Methodology: A multicenter, retrospective medication use evaluation was performed for patients diagnosed with acute ischemic stroke who received alteplase six months prior to formulary thrombolytic conversion, or tenecteplase six months post-transition. Patients were included if they were eighteen years and older with an acute ischemic stroke and received a thrombolytic. Primary outcomes included rate of symptomatic intracranial hemorrhagic transformation, rate of major hemorrhage other than intracranial, and door-to-needle time. Secondary outcomes included changes in National Institutes of Health Stroke Scale at 24 hours and at discharge, modified Rankin Scale at discharge, incidence of dosing errors, door-to-puncture and door-to-device times, and order-to-administration time. Results: Of the 214 patients reviewed, 105 received alteplase and 109 received tenecteplase in a period of six months pre- and post- thrombolytic conversion, respectively. The primary outcome of symptomatic intracranial hemorrhagic complications occurred in 1 patient (1%) that received alteplase compared to 3 patients (3%) that received tenecteplase (p = 0.8). No patients experienced extracranial hemorrhage. Median door-to-needle time was 26 minutes with alteplase and 24 minutes with tenecteplase comprehensive stroke centers (p = 0.22); but longer at primary stroke centers. Median change in NIHSS at 24 hours was 6 points with alteplase and 4 points with tenecteplase across all centers. Median change in NIHSS at discharge was 6 points and 4 points across all centers for alteplase and tenecteplase, respectively. Median order-to-administration time across all centers was 4 minutes with alteplase and 3 minutes with tenecteplase. Most patients, regardless of thrombolytic received, were discharged home and there was no statistically significant difference between discharge dispositions with either thrombolytic. Conclusion: Conversion from alteplase to tenecteplase across a large health system demonstrated both safe and efficacious outcomes. There was no statistical difference in symptomatic intracranial or extracranial hemorrhagic complications, and no patients experienced life-threatening or non-life-threatening extracranial hemorrhage after receiving either thrombolytic for acute ischemic stroke. Factors that could have contributed to differences in metrics include the impact of assessing a new process compared to an established workflow, staff training and turnover, as well as lower stroke volume at non-comprehensive stroke centers