Fibrinolytic Status and Risk of Death After Acute Pulmonary Embolism.

BACKGROUND: Acute pulmonary embolism (PE) is a heterogeneous disease process with variable presentation and outcomes. The endogenous fibrinolytic system is a complex framework of regulatory pathways that maintains homeostasis by dissolving overabundant thrombi. We sought to investigate phenotypic profiles of the endogenous fibrinolytic system among patients presenting with acute PE and their impact on mortality. METHODS: We enrolled all consecutive patients with acute PE in our institutional Pulmonary Embolism Response Team registry. We collected blood samples at the time of PE diagnosis and analyzed concentrations of plasminogen activator inhibitor 1 (PAI-1), thrombin-activatable fibrinolysis inhibitor (TAFI), and alpha-2-antiplasmin (A2A). We assessed the association of concentration of fibrinolytic inhibitors and 1-year all-cause mortality and various echocardiographic markers of right ventricular (RV) dysfunction. RESULTS: There is significant variability of PAI-1, A2A, and TAFI concentrations across the spectrum of PE risk profiles with high PAI-1, low TAFI, and low A2A (herein referred to as a high-risk biomarker profile) correlating with worse PE severity. High-risk biomarker profile correlated with high-risk echocardiographic features of RV dysfunction, including increased RV/left ventricular (LV) ratio, low tricuspid annular plane systolic excursion, and low right ventricular outflow tract velocity time integral. Higher-risk biomarker profile was able to discriminate and independently identify patients at high risk of all-cause mortality (Group 2 HR 6 95% CI 1.3-27.8, Group 3 HR 12, 95% CI 1.7-86). CONCLUSIONS: Further studies are needed to assess the exact pathophysiological link between fibrinolytic status and poor outcome after acute PE and to ascertain the impact of anti-inhibitors of the fibrinolytic system on response to therapy and outcomes after acute PE.

Impact of Pulmonary Embolism Response Team on Anticoagulation Prescribing Patterns in Patients With Acute Pulmonary Embolism.

INTRODUCTION: Anticoagulation remains the mainstay pharmacotherapy for acute pulmonary embolism (PE), but multiple treatment options exist. The Pulmonary Embolism Response Team (PERT) is a multidisciplinary group that evaluates patients, formulates evidence-based treatment plans, and mobilizes resources. The objective of this study was to characterize the anticoagulation prescribing patterns made by PERT and to determine the clinical impact of anticoagulant selection. MATERIALS AND METHODS: This was a retrospective analysis of patients evaluated by PERT from 2016 to 2018. Multivariable linear regression was conducted to determine predictors of length of stay (LOS). RESULTS: A total of 209 patients were evaluated by PERT and received anticoagulation on discharge. Of those, 47% received a non-vitamin K oral anticoagulant (NOAC), 29% received warfarin, and 23% received low-molecular-weight heparin. Patient preferences and comorbidities were the most common reasons for NOAC omission. Patients who received NOACs had a shorter median LOS than warfarin (6.1 [4.6-7.6] days vs 10.9 [8.4-13.4] days; P < .05). Selection of NOAC upon discharge was the only factor independently associated with reduced LOS (ß coefficient: -0.6; 95% CI: -1.01 to -0.18; P < .01). CONCLUSION: The most common recommendation made by PERT was to initiate a NOAC upon discharge, resulting in shorter hospital LOS compared to patients who received warfarin.

Four-factor Prothrombin Complex Concentrate for Reversal of Factor Xa Inhibitors versus Warfarin in Life-threatening Bleeding.

INTRODUCTION: Factor Xa (fXa) inhibitor reversal for life-threatening bleeding is controversial due to a lack of high-quality evidence. The purpose of this study was to determine the hemostatic efficacy of four-factor prothrombin complex concentrate (4F-PCC) for the reversal of fXa inhibitors compared to warfarin for life-threatening bleeding. METHODS: This was a multicenter, retrospective cohort study at two academic medical centers between January 1, 2014-December 31, 2019, which included patients who presented to the emergency department with a life-threatening bleed necessitating anticoagulation reversal with 4F-PCC. The primary endpoint was achievement of hemostatic efficacy after 4F-PCC administration. RESULTS: Of the 525 patients who had an order for 4F-PCC during the study period, 148 patients met the criteria for inclusion (n = 48 fXa inhibitor group; n = 100 warfarin group). Apixaban (52.1%) and rivaroxaban (45.8%) were the most commonly used fXa inhibitors. Effective hemostasis was similar between groups (79.2% fXa inhibitor group vs 85% warfarin group, p = 0.38). This was consistent across all types of bleeding. Thrombotic events were rare in both groups (2% vs 3%). CONCLUSION: This multicenter, retrospective cohort study demonstrated that using 4F-PCC for treatment of life-threatening bleeding produced effective hemostasis in patients on fXa inhibitors and warfarin.

Angiopoietin-2 correlates with pulmonary embolism severity, right ventricular dysfunction, and intensive care unit admission.

Risk stratification of acute pulmonary embolism (PE) is important to identify patients at risk for hemodynamic collapse who would benefit from more aggressive therapies. Angiopoietin-2 (Ang-2) is a signaling molecule involved in angiogenesis and is upregulated in response to tissue hypoxia. We aimed to assess the association of Ang-2 with (1) PE severity, (2) echocardiographic and invasive hemodynamic markers of right ventricular (RV) dysfunction, and (3) need for intensive treatment. Patients presenting to our institution with acute PE were included in a prospective database and blood samples were collected and stored for later analysis. A total of 65 patients were included in the study. Ang-2 correlated with PE risk stratification and echocardiographic and invasive hemodynamic markers of RV dysfunction and pulmonary hypertension. An Ang-2 level of > 4101 pg/mL had an odds ratio of 7.4 (95% CI: 1.53-12.5, p < 0.01) for intensive care unit (ICU) admission. In conclusion, Ang-2 correlates with PE severity, RV dysfunction, and need for ICU admission. Ang-2 holds promise as a novel marker that can aid in risk stratification for this patient population.

Lower socioeconomic factors are associated with higher mortality in patients with septic shock.

BACKGROUND: Previous studies have explored the relationship between socioeconomic status and sepsis outcomes OBJECTIVES: The purpose of this investigation is to determine if race, ethnicity, economic stability, neighborhood environment, and access to health care are predictive of mortality in patients with septic shock. METHODS: Retrospective study of septic shock patients admitted to two medical centers. RESULTS: Caucasian patients had higher proportion of outpatient physician visits in the year prior to admission and were less likely to be Medicare or Medicaid beneficiaries. Thirty-day mortality was lower for the Caucasian cohort (39.3% vs. 48.7%, p < 0.01). Multivariate logistic regression found several predictors of 30-day mortality including Minority race/ethnicity (OR 1.44, 95% CI 1.12-1.86), unemployment (OR 1.40, 95% CI 1.09-1.81), and neighborhood poverty rate ≥10% (OR 1.43, 95% CI 1.01-2.01). CONCLUSIONS: Minority patients, unemployed patients, and those living in neighborhoods with poverty rates greater than 10% suffered from higher 30-day mortality when admitted for septic shock.

Difficulties of Managing Submassive and Massive Pulmonary Embolism in the Era of COVID-19.

Acute pulmonary embolism (PE) is a potentially life-threatening manifestation of venous thromboembolic disease. Severe acute respiratory syndrome-coronavirus-2, a novel coronavirus that causes coronavirus disease-2019 (COVID-19), has been associated with an increased risk of thrombosis. We describe the therapeutic challenges of 3 patients presenting with PE and suspected or confirmed COVID-19. (Level of Difficulty: Beginner.).

Pulmonary embolism response team implementation improves awareness and education among the house staff and faculty.

A subset of high-risk pulmonary embolism (PE) patients requires advanced therapy beyond anticoagulation. Significant variation in delivery of care has led institutions to standardize their approach by developing Pulmonary Embolism Response Team (PERT). We sought to assess the impact of PERT implementation on house staff and faculty education. After implementation of PERT, we employed a targeted educational intervention aimed to improve PERT awareness, familiarity with treatment options, role of echocardiogram and Doppler ultrasound, and knowledge of acute PE risk stratification tools. We conducted an anonymous survey among the house staff and faculty before and after intervention to assess the impact of PERT implementation on educational objectives among clinicians. Initial and follow up samples included 115 and 109 responses. The samples were well represented across the subspecialties and all levels of training, as well as junior and senior faculty. Following the educational campaign, awareness of the program increased (72.2-92.6%, p < 0.01). Proportion of clinicians with reported comfort level of managing PE increased (82.4-90.8%, p = 0.07). Proportion of clinicians with self-reported comfort with explaining all available treatment modalities to patients increased (49.1-67.9%, p = 0.005). Proportions of responders who correctly identified the role of echocardiography in risk stratification of patients with known PE increased (73.9-84.4%, p = 0.07). Accurate clinical risk stratification of acute PE increased (60.2-73.8%, p = 0.03). The implementation of a targeted educational program at a tertiary care center increased awareness of PERT among house staff and faculty and improved physician's accuracy of clinical risk stratification and comfort level with management of acute PE.

Delayed vasopressor initiation is associated with increased mortality in patients with septic shock.

PURPOSE: Mortality rate for septic shock, despite advancements in knowledge and treatment, remains high. Treatment includes administration of broad-spectrum antibiotics and stabilization of the mean arterial pressure (MAP) with intravenous fluid resuscitation. Fluid-refractory shock warrants vasopressor initiation. There is a paucity of evidence regarding the timing of vasopressor initiation and its effect on patient outcomes. MATERIALS AND METHODS: This retrospective, single-centered, cohort study included patients with septic shock from January 2017 to July 2017. Time from initial hypotension to vasopressor initiation was measured for each patient. The primary outcome was 30-day mortality. RESULTS: Of 530 patients screened,119 patients were included. There were no differences in baseline patient characteristics. Thirty-day mortality was higher in patients who received vasopressors after 6 h (51.1% vs 25%, p < .01). Patients who received vasopressors within the first 6 h had more vasopressor-free hours at 72 h (34.5 h vs 13.1, p = .03) and shorter time to MAP of 65 mmHg (1.5 h vs 3.0, p < .01). CONCLUSION: Vasopressor initiation after 6 h from shock recognition is associated with a significant increase in 30-day mortality. Vasopressor administration within 6 h was associated with shorter time to achievement of MAP goals and higher vasopressor-free hours within the first 72 h.

Right Ventricular Outflow Doppler Predicts Low Cardiac Index in Intermediate Risk Pulmonary Embolism.

Intermediate-risk pulmonary embolism (PE) has variable outcomes. Current risk stratification models lack the positive predictive value to identify patients at highest risk of PE-related mortality. We identified intermediate-risk PE patients who underwent catheter-based interventions and right heart catheterization (RHC) and identified those with low cardiac index (CI < 2.2 L/min/m2). We utilized regression models to identify echocardiographic predictors of low CI and Kaplan Meier curve to evaluate PE-related mortality when stratified by the echocardiographic predictor. Of 174 intermediate-risk PE patients, 41 underwent RHC. Within this cohort, 46.3% had low CI. Univariable linear regression identified right ventricular outflow tract velocity time integral (RVOT VTI), right/left ventricular ratio, S prime, inferior vena cava diameter, and pulmonary artery systolic pressure as potential predictors of low CI. Multivariable linear regression identified RVOT VTI as significant predictor of low CI (ß coefficient 0.124, 95% confidence interval [CI]: 0.01-0.24, P = .034). Right ventricular outflow tract velocity time integral <9.5 cm was associated with increased PE-related mortality, P = .002. A substantial proportion of intermediate-risk PE patients referred for catheter-based interventions had low CI despite normotension. Right ventricular outflow tract velocity time integral was a significant predictor of low CI. Low RVOT VTI was associated with increased PE-related mortality.

Pharmacist Presence Decreases Time to Prothrombin Complex Concentrate in Emergency Department Patients with Life-Threatening Bleeding and Urgent Procedures.

BACKGROUND: Reversal of anticoagulation with four-factor prothrombin complex concentrate (4F-PCC) is critical, yet the optimal timing to 4F-PCC administration and whether quicker administration improves hemostasis remains unknown. OBJECTIVE: The objective of this study was to determine if pharmacist presence is predictive of faster time to 4F-PCC. METHODS: This retrospective cohort study included patients receiving 4F-PCC for life-threatening bleeding or urgent procedure in the emergency department (ED) from 2014 to 2018. Patients with pharmacists at bedside (PharmD group) were compared with physician teams alone (control group). The primary outcome was time from ED presentation to 4F-PCC administration. RESULTS: Of 252 patients evaluated, 116 patients (46%) were included (n = 50 PharmD group; n = 66 control group). Most patients presented on warfarin (68.1%), and of the life-threatening bleeds (94%), intracranial hemorrhage was most common (67.2%). The median time to 4F-PCC administration was significantly shorter in the PharmD group (66.5 vs. 206.5 min, p < 0.001). Pharmacist at bedside was the only factor independently associated with reduction in time to 4F-PCC (ß coefficient -163.5 min, 95% confidence interval -249.4 to -77.7). Although there was no difference in hemostasis or mortality, patients in the PharmD group had a shorter intensive care unit length of stay (LOS) (2 vs. 5 days, p < 0.01) and hospital LOS (5.5 vs. 8 days, p = 0.02). CONCLUSION: A pharmacist at the bedside of patients who present to the ED with life-threatening bleeding or need for emergent procedure decreased time to 4F-PCC administration by 140 min, even after accounting for confounders. Faster time to 4F-PCC was associated with significantly shorter intensive care unit and hospital LOS.

Intravenous Lidocaine for Acute Pain: A Systematic Review.

This systematic review evaluates the safety and efficacy of intravenous (IV) lidocaine for the treatment of acute pain in adult patients. The PubMed database was searched for randomized controlled trials, retrospective cohort studies, case series, and case reports evaluating the use of IV lidocaine for the treatment of acute pain in adult patients, published between January 1970 and January 2018. The primary outcome was pain reduction via the Visual Analog Scale, Verbal Rating Scale, or Numeric Rating Scale among patients treated with IV lidocaine and placebo or active controls. Safety outcomes included both nonserious and serious adverse events. A total of 347 titles and abstracts were screened, and after full-text review, 13 studies met the inclusion criteria involving 512 patients. The four active controls studied were IV morphine, IV ketorolac, IV dihydroergotamine (DHE), and IV chlorpromazine (CPZ). The dosing of IV lidocaine varied among studies between a weight-based dose of a 1- to 2-mg/kg bolus, a fixed-bolus dose of 50-100 mg, and a 1-mg/kg/hour continuous infusion. Monitoring of serum lidocaine concentrations was not done routinely. Intravenous lidocaine had superior efficacy to morphine for renal colic and critical limb ischemia, superior efficacy to DHE for acute migraine, and equivalent efficacy to ketorolac for acute radicular lower back pain. However, lidocaine was less effective than CPZ for the treatment of acute migraine. The most common adverse event reported among all studies were neurologic effects such as altered mental status and slurred speech. Due to the inconsistency in dosing, length of administration, and lack of serum monitoring, the absolute safety of IV lidocaine for acute pain is unknown. Larger, prospective studies are needed before the routine use of IV lidocaine can be recommended for all types of acute pain.

Traditional matriculation vs an early assurance program: Effect on elected student leadership positions and academic performance.

INTRODUCTION: The objective of this study was to compare leadership and academic performance among students admitted by traditional pathways vs. a dual acceptance program (DAP). METHODS: A list of students admitted to the Midwestern University Chicago College of Pharmacy (MWUCCP) DAP was cross-checked with students elected to serve in leadership positions and students on the MWUCCP Dean's List for their first professional year from 2010 to 2015. The proportion of students serving in leadership positions and those on the Dean's List were compared to students that matriculated via the traditional route. RESULTS: In total, 1069 students were analyzed (n = 937 traditional; n = 132 DAP). DAP students were more likely to have an elected leadership role (n = 61, 46.2% vs. n = 314, 33.5%, p < 0.01) and achieve Dean's List for their first professional year (n = 64, 48.5% vs. n = 292, 31.2%, p < 0.01) compared to traditional students. DISCUSSION AND CONCLUSIONS: DAP students were more likely to hold an elected leadership position than traditional students. Further study of DAP student motivation is needed to potentially assist in the success of other students.

Analysis of PGY-1 Pharmacy Resident Candidate Letters of Recommendation at an Academically Affiliated Residency Program.

BACKGROUND: Letters of recommendation (LORs) are a critical component for differentiating among similarly qualified pharmacy residency candidates. These letters contain information that is difficult to ascertain from curricula vitae and pharmacy school transcripts. LOR writers may use any words or phrases appropriate for each candidate as there is no set framework for LORs. OBJECTIVE: The objective of this study was to characterize descriptive themes in postgraduate year 1 (PGY-1) pharmacy residency candidates' LORs and to examine which themes of PGY-1 pharmacy residency candidates' LORs are predictive of an interview invitation at an academically affiliated residency program. METHODS: LORs for candidates from the Pharmacy Online Residency Centralized Application System (PhORCAS) from 2013 and 2014 for the Midwestern University PGY-1 Pharmacy Residency were analyzed. LOR characteristics and descriptive themes were collected. All scores for candidate characteristics and overall PhORCAS recommendation were also recorded. RESULTS: A total of 351 LORs for 111 candidates from 2013 (n = 47 candidates) and 2014 (n = 64 candidates) were analyzed; 36 (32.4%) total candidates were offered an interview. Themes that were identified as predictors of an interview included a higher median (interquartile range) number of standout words (3 words [1.3-4] vs 3.8 words [2.5-5.5], P < .01) and teaching references (3.7 words [2.7-6] vs 5.7 words [3.7-7.8], P = .01). CONCLUSION: For this residency program, standout words and teaching references were important when offering interviews.

Implementation of a pharmacy research committee to enhance the pharmacy resident research experience.

BACKGROUND AND PURPOSE: Most postgraduate year 1 (PGY1) pharmacy residents complete at least one research project as part of their graduation requirements. The research skills learned prepare residents to address research questions and generate evidence-based recommendations for patient care. However, there are multiple steps involved in a research project, and streamlining this process can be difficult. EDUCATIONAL ACTIVITY AND SETTING: Northwestern Memorial Hospital (NMH), a large academic center located in Chicago, IL, developed a research committee (RC) to facilitate research within the department of pharmacy for residents and to maintain residency research support materials. These materials included a charter to help guide the organizational structure and operations of the RC, research timelines, and a seminar series. FINDINGS: The RC works to ensure that the residents overcome any challenges that they may incur during their research projects by setting clear expectations and milestones. Feedback is provided by the residents and incorporated into the research process and support materials. DISCUSSION: The RC allows for individualized attention and personalization of the research experience for each resident. The program endeavors each year to provide the message that publication should be the final goal of a research project and not presentation at a conference. SUMMARY: Pharmacy residents receive support from the RC from throughout the year, not only when issues surround their project arise. Institutions may implement or modify existing programs based upon the resources provided.