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Background: Intracranial hemorrhage (ICH) is a serious complication associated with oral anticoagulant use and is associated with significant morbidity and mortality. Although anticoagulation reversal agents are utilized as standard of care, practitioners are limited in their ability to assess degree of anticoagulation reversal for direct oral anticoagulants (DOACs). There is a clinical need identify biomarkers to assess anticoagulation status in patients with DOAC-associated ICH to ensure hemostatic efficacy of anticoagulation reversal agents in the acute setting. The purpose of this study was to assess the utility of thromboelastography (TEG) to assess the impact of anticoagulation reversal in patients presenting to the emergency department (ED) with DOAC-associated ICH., Methods: We conducted a prospective, observational cohort study in adult patients presenting to the ED with acute DOAC-associated ICH. Patients were excluded if last DOAC dose was >48 hours prior to hospital arrival, if they experienced polytrauma, were pregnant, incarcerated, had a history of hepatic failure or coagulopathy, or received anticoagulation reversal with products other than prothrombin complex concentrates (PCCs). We collected baseline TEG samples from participants prior to anticoagulation reversal, as well as 30-minutes, 12-hours, and 24-hours post-reversal. TEG samples were also collected from participants who transferred to our facility after reversal at ED presentation, as well as 12- and 24-hours post-reversal., Results: Pre-reversal TEG was collected on 10 participants prior to DOAC reversal. A significant decrease in TEG R-time was observed at 30 minutes post-reversal. R-time increased at 12- and 24-hours to baseline levels. Significant changes were not observed in K-time, clot strength, maximum amplitude, or coagulation index., Conclusions: TEG R-time may be able to detect a change in anticoagulation activity of DOACs in ICH after anticoagulation reversal. R-time decreases acutely after anticoagulation reversal and rebounds at 12- and 24-hours post-reversal.

Objective: To review the efficacy, safety, and place in therapy of fentanyl as an induction agent for rapid sequence intubation (RSI) in critically ill patients. Data Sources: A comprehensive search of PubMed, EMBASE, and clinical trial registries (1964-June 2021) was performed utilizing the keywords fentanyl, rapid sequence intubation, intubation, induction, anesthesia, hemodynamics, operating room (OR), and emergency. Study Selection and Data Extraction: Only primary literature evaluating fentanyl in combination with a sedative or as the sole induction agent was included in the final analysis. Primary literature included peer-reviewed publications and results posted on ClinicalTrials.gov actively recruiting participants. Data Synthesis: Fentanyl has been used for decades as an adjunct, and sole induction agent in the OR. Questions surrounding the use of fentanyl as a sole induction agent include optimal dosing and safety in critically ill patients as evaluation in non-OR settings remain limited. Relevance to Patient Care and Clinical Practice: Commonly used induction agents (eg, etomidate and ketamine) are associated with adverse events that may increase risk of morbidity and mortality. Fentanyl, a high-potency opioid could serve as an alternative induction agent for RSI due to its neutral hemodynamic response and fast onset of action. This paper compiles and describes existing data on the use of fentanyl as an induction agent for RSI. Conclusion: Fentanyl in combination with sedatives provides optimal intubating conditions with minimal impact on hemodynamic parameters. Future studies should focus on safety and impact of awareness during paralysis before fentanyl can be considered as a sole induction agent., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. FundingThe author(s) received no financial support for the research, authorship, and/or publication of this article.

Background: Urinary tract infections (UTIs) are commonly treated in the emergency department (ED), and unfortunately, resistance to first-line agents is increasing., Objectives: To characterize treatment of pyelonephritis in a nationally representative sample of ED patients and to identify patient- and treatment-specific factors associated with receiving initial inactive antibiotics., Methods: We conducted a multicentre, observational cohort study utilizing the Emergency Medicine PHARMacotherapy Research NETwork (EMPHARM-NET), comprising 15 geographically diverse US EDs. All patients ≥18 years of age with a diagnosis of pyelonephritis between 2018 and 2020 were included. The primary endpoint was the proportion of patients who received initial inactive empirical antibiotic therapy and to identify predictive factors of inactive antibiotic therapy., Results: Of the 3714 patients evaluated, 223 had culture-positive pyelonephritis. Median patient age was 50.1 years and patients were mostly female (78.3%). Overall, 40.4% of patients received an IV antibiotic, most commonly ceftriaxone (86.7%). The most frequently prescribed antibiotics were cefalexin (31.8%), ciprofloxacin (14.3%), cefdinir (13.5%) and trimethoprim/sulfamethoxazole (12.6%). Overall, 10.3% of patients received initial inactive therapy. After adjustment in a multivariable analysis, long-acting IV antibiotic was predictive of inactive therapy (OR 0.23, 95% CI 0.07-0.83)., Conclusions: In our prospective, multicentre observational study, we found that only 40.4% of patients with pyelonephritis received empirical IV antibiotics in the ED, contributing to inactive therapy. Receipt of long-acting IV antibiotics was independently associated with a decreased rate of initial inactive therapy. This reinforces guideline recommendations to administer long-acting IV antibiotics empirically in the ED upon suspicion of pyelonephritis., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Purpose: The preferred vasopressor in post-cardiac arrest shock has not been established with robust clinical outcomes data. Our goal was to perform a systematic review and meta-analysis comparing rates of in-hospital mortality, refractory shock, and hemodynamic parameters in post-cardiac arrest patients who received either norepinephrine or epinephrine as primary vasopressor support., Methods: We conducted a search of PubMed, Cochrane Library, and CINAHL from 2000 to 2022. Included studies were prospective, retrospective, or published abstracts comparing norepinephrine and epinephrine in adults with post-cardiac arrest shock or with cardiogenic shock and extractable post-cardiac arrest data. The primary outcome of interest was in-hospital mortality. Other outcomes included incidence of arrhythmias or refractory shock., Results: The database search returned 2646 studies. Two studies involving 853 participants were included in the systematic review. The proposed meta-analysis was deferred due to low yield. Crude incidence of in-hospital mortality was numerically higher in the epinephrine group compared with norepinephrine in both studies, but only statistically significant in one. Risk of bias was moderate to severe for in-hospital mortality. Additional outcomes were reported differently between studies, minimizing direct comparison., Conclusion: The vasopressor with the best mortality and hemodynamic outcomes in post-cardiac arrest shock remains unclear. Randomized studies are crucial to remedy this., Competing Interests: Declaration of Competing Interest The following authors report no conflict of interest: CL, CC, NA, LR. The following authors received funding by Spero Therapeutics-provided unrestricted research grant via its Investigator Initiated Research Program: BF, MR, GS. GS reports participating in an advisory board meeting for Hema Biologics in 2022 regarding blood factor products. CB reports grant funding from Alexion/Astra Zeneca Rare Disease., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: In 2009, researchers successfully implemented an intervention to decrease the inappropriate prescribing of multivitamin infusions (MVIs) in the emergency department (ED) for patients presenting with alcohol-related illnesses. Objective: The purposes of our study were to determine the impact of the 2009 intervention on hospital-wide prescribing practices of vitamin therapies for alcohol-related illnesses, and to evaluate its long-term sustainability. Methods: A retrospective observational cohort study was conducted at a 60,000-visit ED, 811-bed academically-affiliated tertiary referral hospital with an average census of 515 and 714 patients in 2009 and 2019, respectively. Patients were included if they presented to the ED from 2009 to 2019 with an alcohol-related illness as defined by ICD-9 and ICD-10 codes. The primary outcome was the change in the monthly average of MVIs ordered inpatient within the first four months compared to the last four months of the study period. Secondary outcomes included changes in the mean distribution (MD) per month of thiamine administrations in the ED and inpatient setting, and MVIs ordered in the ED. Results: The MD of MVIs ordered per month decreased by 3.5% (95% CI -5.3, -1.7) in the inpatient setting and decreased by 1.4% (95% CI -2.5, -.3) in the ED from the beginning to the end of our study period. Conclusions: This study suggests the effects of an intervention made in the ED sustained impact over a 10-year timeframe, and decreased the use of MVIs in both the ED and hospital-wide., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Importance: A patient's belief in the likely success of a treatment may influence outcomes, but this has been understudied in surgical trials., Objective: To examine the association between patients' baseline beliefs about the likelihood of treatment success with outcomes of antibiotics for appendicitis in the Comparison of Outcomes of Antibiotic Drugs and Appendectomy (CODA) trial., Design, Setting, and Participants: This was a secondary analysis of the CODA randomized clinical trial. Participants from 25 US medical centers were enrolled between May 3, 2016, and February 5, 2020. Included in the analysis were participants with appendicitis who were randomly assigned to receive antibiotics in the CODA trial. After informed consent but before randomization, participants who were assigned to receive antibiotics responded to a baseline survey including a question about how successful they believed antibiotics could be in treating their appendicitis., Interventions: Participants were categorized based on baseline survey responses into 1 of 3 belief groups: unsuccessful/unsure, intermediate, and completely successful., Main Outcomes and Measures: Three outcomes were assigned at 30 days: (1) appendectomy, (2) high decisional regret or dissatisfaction with treatment, and (3) persistent signs and symptoms (abdominal pain, tenderness, fever, or chills). Outcomes were compared across groups using adjusted risk differences (aRDs), with propensity score adjustment for sociodemographic and clinical factors., Results: Of the 776 study participants who were assigned antibiotic treatment in CODA, a total of 425 (mean [SD] age, 38.5 [13.6] years; 277 male [65%]) completed the baseline belief survey before knowing their treatment assignment. Baseline beliefs were as follows: 22% of participants (92 of 415) had an unsuccessful/unsure response, 51% (212 of 415) had an intermediate response, and 27% (111 of 415) had a completely successful response. Compared with the unsuccessful/unsure group, those who believed antibiotics could be completely successful had a 13-percentage point lower risk of appendectomy (aRD, -13.49; 95% CI, -24.57 to -2.40). The aRD between those with intermediate vs unsuccessful/unsure beliefs was -5.68 (95% CI, -16.57 to 5.20). Compared with the unsuccessful/unsure group, those with intermediate beliefs had a lower risk of persistent signs and symptoms (aRD, -15.72; 95% CI, -29.71 to -1.72), with directionally similar results for the completely successful group (aRD, -15.14; 95% CI, -30.56 to 0.28)., Conclusions and Relevance: Positive patient beliefs about the likely success of antibiotics for appendicitis were associated with a lower risk of appendectomy and with resolution of signs and symptoms by 30 days. Pathways relating beliefs to outcomes and the potential modifiability of beliefs to improve outcomes merit further investigation., Trial Registration: ClinicalTrials.gov Identifier: NCT02800785.

Purpose: Despite the expertise that emergency medicine (EM) pharmacists bring to multidisciplinary teams in the emergency department (ED) setting, they are not commonly present on writing groups for guidelines, policies, or task forces pertaining to EM pharmacotherapy. The purpose of this article is to quantify EM pharmacist involvement on author bylines of guidelines, position statements, and other official documents that specifically encompass EM pharmacotherapy., Methods: Official work products released between January 1, 2010, and May 1, 2021, were collected from the American College of Emergency Physicians (ACEP), Society for Academic Emergency Medicine (SAEM), and American Academy of Emergency Medicine (AAEM) and the table of contents of the following journals: Annals of Emergency Medicine, Academic Emergency Medicine, and Journal of Emergency Medicine. A modified Delphi approach was used to gain consensus amongst the authors on which work products to include in the initial review and which works pertained to pharmacotherapy. The primary endpoint was the percentage of pharmacists listed as authors on EM work products pertaining to pharmacotherapy., Results: Overall, 76 EM work products were identified. Forty-seven work products with a total of 248 authors contained at least 1 recommendation pertaining to pharmacotherapy. Of these 47 EM work products, 23 (49%) were from AAEM, 16 (34%) were from Annals of Emergency Medicine (published on behalf of ACEP), 5 (11%) were from Journal of Emergency Medicine (published on behalf of AAEM), and 3 (6%) were from SAEM. The median number of authors per work product was 4. There were 5 pharmacists listed on work products (2% of the total of 248 authors). Additionally, there were 9 nonpharmacist/nonphysician authors (4% of the total)., Conclusion: Pharmacist inclusion on author lists of recently published EM work products pertaining to pharmacotherapy is extremely low. Given their unique knowledge pertaining to EM pharmacotherapy, an effort should be made to increase inclusion of pharmacists as authors of EM work products with recommendations that pertain to pharmacotherapy., (© American Society of Health-System Pharmacists 2022. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Uropathogen resistance, fluoroquinolone-resistance (FQR), and extended spectrum beta-lactamase (ESBL), has been observed to be emerging worldwide with prevalences above recommended thresholds for routine empirical treatment. The primary aim of our study was to determine the prevalence of FQR from a geographically diverse sample of United States emergency departments (EDs)., Methods: We conducted a multi-center, observational cohort study using a network of 15 geographically diverse US EDs. All patients ≥18 years of age with the primary or secondary diagnosis of urinary tract infection (UTI) in the ED identified using International Classification of Diseases (ICD-10) diagnosis code of cystitis, pyelonephritis, or UTI from 2018 to 2020 were included. We calculated descriptive statistics for uropathogens and susceptibilities. Logistic regression analysis was used to identify antimicrobial resistance risk factors associated with FQR Escherichia coli., Results: Among 3779 patients who met inclusion criteria, median age was 62.9 years (interquartile range [IQR]: 41-77.6) and 76.3% were female. The most common diagnoses were complicated (41.2%) and uncomplicated cystitis (40.3%). E. coli was the most common pathogen (63.2%), followed by Klebsiella pneumoniae (13.2%) and Enterococcus species (5.8%). Across all sites, overall E. coli FQ-resistance prevalence was 22.1%, ranging from 10.5 to 29.7% by site. The prevalence of ESBL-producing uropathogen was 7.4%, ranging from 3.6% to 11.6% by site. Previous IV or oral antimicrobial use in the past 90-days and history of a multi-drug resistant pathogen were associated with FQ-resistant E. coli (odds ratio [OR] 2.68, 95% confidence interval [CI]: 2.04-3.51, and OR 6.93, 95% CI: 4.95-9.70, respectively). Of the patients who had FQ-resistant E. coli or an ESBL-producing uropathogen isolated, 116 (37.1%) and 61 (36.7%) did not have any documented risk factors for resistance., Conclusion: FQ-resistant E. coli is widely prevalent across US sites highlighting the need for ongoing monitoring of antimicrobial resistance and, at some locations, modification of empirical treatments., (© 2022 The Authors. Academic Emergency Medicine published by Wiley Periodicals LLC on behalf of Society for Academic Emergency Medicine.)

Importance: In the Comparison of Outcomes of Antibiotic Drugs and Appendectomy (CODA) trial, which found antibiotics to be noninferior, approximately half of participants randomized to receive antibiotics had outpatient management with hospital discharge within 24 hours. If outpatient management is safe, it could increase convenience and decrease health care use and costs., Objective: To assess the use and safety of outpatient management of acute appendicitis., Design, Setting, and Participants: This cohort study, which is a secondary analysis of the CODA trial, included 776 adults with imaging-confirmed appendicitis who received antibiotics at 25 US hospitals from May 1, 2016, to February 28, 2020., Exposures: Participants randomized to antibiotics (intravenous then oral) could be discharged from the emergency department based on clinician judgment and prespecified criteria (hemodynamically stable, afebrile, oral intake tolerated, pain controlled, and follow-up confirmed). Outpatient management and hospitalization were defined as discharge within or after 24 hours, respectively., Main Outcomes and Measures: Outcomes compared among patients receiving outpatient vs inpatient care included serious adverse events (SAEs), appendectomies, health care encounters, satisfaction, missed workdays at 7 days, and EuroQol 5-dimension (EQ-5D) score at 30 days. In addition, appendectomy incidence among outpatients and inpatients, unadjusted and adjusted for illness severity, was compared., Results: Among 776 antibiotic-randomized participants, 42 (5.4%) underwent appendectomy within 24 hours and 8 (1.0%) did not receive their first antibiotic dose within 24 hours, leaving 726 (93.6%) comprising the study population (median age, 36 years; range, 18-86 years; 462 [63.6%] male; 437 [60.2%] White). Of these participants, 335 (46.1%; site range, 0-89.2%) were discharged within 24 hours, and 391 (53.9%) were discharged after 24 hours. Over 7 days, SAEs occurred in 0.9 (95% CI, 0.2-2.6) per 100 outpatients and 1.3 (95% CI, 0.4-2.9) per 100 inpatients; in the appendicolith subgroup, SAEs occurred in 2.3 (95% CI, 0.3-8.2) per 100 outpatients vs 2.8 (95% CI, 0.6-7.9) per 100 inpatients. During this period, appendectomy occurred in 9.9% (95% CI, 6.9%-13.7%) of outpatients and 14.1% (95% CI, 10.8%-18.0%) of inpatients; adjusted analysis demonstrated a similar difference in incidence (-4.0 percentage points; 95% CI, -8.7 to 0.6). At 30 days, appendectomies occurred in 12.6% (95% CI, 9.1%-16.7%) of outpatients and 19.0% (95% CI, 15.1%-23.4%) of inpatients. Outpatients missed fewer workdays (2.6 days; 95% CI, 2.3-2.9 days) than did inpatients (3.8 days; 95% CI, 3.4-4.3 days) and had similar frequency of return health care visits and high satisfaction and EQ-5D scores., Conclusions and Relevance: These findings support that outpatient antibiotic management is safe for selected adults with acute appendicitis, with no greater risk of complications or appendectomy than hospital care, and should be included in shared decision-making discussions of patient preferences for outcomes associated with nonoperative and operative care., Trial Registration: ClinicalTrials.gov Identifier: NCT02800785.

Background: Methicillin-resistant Staphylococcus aureus (MRSA) nasal swab polymerase chain reaction (PCR) assay has a 96.1-99.2% negative predictive value (NPV) in pneumonia and may be used for early de-escalation of MRSA-active antibiotic agents. Xu (2018), File (2010) [1,2]., Objective: The objective of our study was to determine if a negative MRSA PCR nasal swab collected in the emergency department (ED) improves early MRSA-active antibiotic de-escalation., Methods: A single center observational cohort study used ICD-10 codes to identify records for adults admitted to the ED with a hospital discharge diagnosis of pneumonia. The primary outcome was proportion of patients with early de-escalation on an MRSA-active agent (≤ 1 dose). Secondary outcomes included rate of acute kidney injury (AKI), positive MRSA cultures (blood culture, respiratory sputum, tracheal aspirate), hospital length of stay (LOS), in-hospital mortality, and 30-day readmission rates., Results: A total of 341 patients were included in the study. Of the patients with an MRSA PCR swab, 35.2% of patients with a negative swab received >1 dose of MRSA-active agent compared to 52% of patients without an MRSA nasal swab (p < 0.01). There were no significant differences in secondary outcomes except readmission rate of 1.6% of patients that did not have an MRSA swab in the ED vs 6.6% of patients that received an MRSA swab in the ED., Conclusion and Relevance: MRSA PCR nasal swabs in the ED may serve as a useful tool for early MRSA-active antibiotic de-escalation when treating pneumonia., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 Elsevier Inc. All rights reserved.)

People who use drugs (PWUD) are at increased risk for drug-related harms such as overdose. Additionally, they are also at increased risk of secondary harms from bacterial and other infections such as hepatitis B, hepatitis C, and Human Immunodeficiency Virus. These secondary harms, along with other medical conditions, typically require treatment with prescription medications. When considering treatment options, drug-drug interactions (DDIs) must be considered, unfortunately these interactions are often overlooked with addictive drugs. Although DDIs in PWUD have been reviewed for certain drug classes and specific drugs of abuse, no comprehensive list could be found. The objective of this article is to compile a list of potential DDIs between prescription drugs and addictive drugs to create a list allowing prescribers to make more informed decisions when prescribing a medication to PWUD., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 American Society of Addiction Medicine.)

Purpose: Oral factor Xa inhibitors (FXaIs) are increasingly utilized for outpatient anticoagulation therapy; however, laboratory monitoring is not routinely used to assess the safety and efficacy of these agents. We aimed to evaluate the role of chromogenic anti-factor Xa (anti-Xa) assays in the emergency department (ED) in the setting of patients with an acute bleed or requiring emergent procedures., Methods: A retrospective review of anti-Xa levels obtained in the ED between June 1, 2019, and April 30, 2020, was completed. Data were collected to describe the clinical setting of anti-Xa level collection, oral FXaIs used before admission, administration of reversal agents, and patient disposition to further characterize the role of anti-Xa levels in the management of rivaroxaban and apixaban reversal., Results: Thirty anti-Xa levels were included in the final analysis. The median time from sample collection to anti-Xa assay result was 45.9 minutes (interquartile range, 35.3-54.7 minutes). Eleven patients (37%) received anticoagulation reversal after their anti-Xa levels were determined. Anticoagulation reversal agents included either activated prothrombin complex concentrates (aPCCs) or prothrombin complex concentrates (PCCs). Anti-Xa levels were collected in 2 patients who had received PCCs before arrival at our ED. Of the patients with anti-Xa levels below 30 ng/mL, none received aPCCs or PCCs after their anti-Xa levels were determined. Anti-Xa assays were used to rule out the presence of FXaIs in 3 patients., Conclusion: This study illustrates the novel role of anti-Xa levels in managing patients with an emergent need for reversal in the ED. The assay may be used to rule out the presence of oral FXaIs and avoid unnecessary administrations of anticoagulation reversal agents., (© American Society of Health-System Pharmacists 2021. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Urinary tract infection (UTI) is a common infectious disease managed in the emergency department (ED). Patients may be initially treated with an intravenous (IV) antibiotic and subsequently discharged with an oral antibiotic regimen., Objective: The purpose of this study was to determine whether the current Infectious Diseases Society of America guideline recommendation for an initial dose of long-acting IV antibiotic for treatment of UTI when the prevalence of fluoroquinolone resistance exceeds 10% improves the likelihood of providing in vitro susceptibility to the isolated uropathogen., Methods: This was a retrospective study of patients in ED presenting between May 2009 and August 2018 who received treatment for UTI. The primary outcome was susceptibility of uropathogen to the IV antibiotic administered. Secondary outcomes included susceptibility to the oral antibiotic regimen prescribed at discharge, repeat health care visit within 30 days related to UTI follow-up, adverse events (AEs) associated with antibiotic use, and identification of risk factors associated with pathogen resistance., Results: A total of 255 patients were included for analysis. Of these patients, 230 (90.2%) had pathogens susceptible to the administered IV antibiotic. The oral regimen susceptibility was 81.6% with 29 patients returning for UTI follow-up and 4 patients reporting AEs related to antibiotic use. Men and long-term care facility residents were more likely to have resistant uropathogens., Conclusion: Administration of a long-acting IV antibiotic for treatment of UTI prior to ED discharge is recommended when the fluoroquinolone resistance rate exceeds 10% to improve in vitro susceptibility coverage., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2020.)

Background: Antibiotic therapy has been proposed as an alternative to surgery for the treatment of appendicitis., Methods: We conducted a pragmatic, nonblinded, noninferiority, randomized trial comparing antibiotic therapy (10-day course) with appendectomy in patients with appendicitis at 25 U.S. centers. The primary outcome was 30-day health status, as assessed with the European Quality of Life-5 Dimensions (EQ-5D) questionnaire (scores range from 0 to 1, with higher scores indicating better health status; noninferiority margin, 0.05 points). Secondary outcomes included appendectomy in the antibiotics group and complications through 90 days; analyses were prespecified in subgroups defined according to the presence or absence of an appendicolith., Results: In total, 1552 adults (414 with an appendicolith) underwent randomization; 776 were assigned to receive antibiotics (47% of whom were not hospitalized for the index treatment) and 776 to undergo appendectomy (96% of whom underwent a laparoscopic procedure). Antibiotics were noninferior to appendectomy on the basis of 30-day EQ-5D scores (mean difference, 0.01 points; 95% confidence interval [CI], -0.001 to 0.03). In the antibiotics group, 29% had undergone appendectomy by 90 days, including 41% of those with an appendicolith and 25% of those without an appendicolith. Complications were more common in the antibiotics group than in the appendectomy group (8.1 vs. 3.5 per 100 participants; rate ratio, 2.28; 95% CI, 1.30 to 3.98); the higher rate in the antibiotics group could be attributed to those with an appendicolith (20.2 vs. 3.6 per 100 participants; rate ratio, 5.69; 95% CI, 2.11 to 15.38) and not to those without an appendicolith (3.7 vs. 3.5 per 100 participants; rate ratio, 1.05; 95% CI, 0.45 to 2.43). The rate of serious adverse events was 4.0 per 100 participants in the antibiotics group and 3.0 per 100 participants in the appendectomy group (rate ratio, 1.29; 95% CI, 0.67 to 2.50)., Conclusions: For the treatment of appendicitis, antibiotics were noninferior to appendectomy on the basis of results of a standard health-status measure. In the antibiotics group, nearly 3 in 10 participants had undergone appendectomy by 90 days. Participants with an appendicolith were at a higher risk for appendectomy and for complications than those without an appendicolith. (Funded by the Patient-Centered Outcomes Research Institute; CODA ClinicalTrials.gov number, NCT02800785.)., (Copyright © 2020 Massachusetts Medical Society.)

Introduction: Febrile neutropenia is an oncologic emergency associated with significant morbidity and mortality. The objective of our study was to assess guideline adherence and clinical outcomes associated with the management of high- and low-risk febrile neutropenia patients presenting to the emergency department., Methods: A retrospective observational cohort study was conducted at a 60,000-visit emergency department at an academically-affiliated tertiary referral hospital. Patients were identified as low- or high-risk using the guideline-recommended Multinational Association for Supportive Care in Cancer score. The primary outcome was the proportion of cases in which the management was concordant with applicable febrile neutropenia guidelines. Guideline adherence was defined as hospital admission and intravenous antimicrobial therapy for high-risk patients and discharge home with oral antimicrobial therapy for low-risk patients. Secondary outcomes included appropriate vancomycin administration, hospital length of stay, rates of acute kidney injury, in-hospital Clostridium difficile infection rates, and 30-day mortality., Results: Of the 237 patients included, 94 (39.7%) were low-risk patients and 143 (60.3%) were high-risk patients. Guideline adherence occurred in 96.8% of high-risk patients and 0.4% of low-risk patients. Mean hospital length of stay of the low-risk group was 5 ± 5.0 days compared to 7.2 ± 7.3 days in the high-risk group. Vancomycin was often inappropriately given in 69.5% of high-risk patients. Clostridium difficile occurred in 15 (10.3%) adherent and 4 (4.4%) non-adherent patients. By 30 days, 4 (4.3%) low-risk and 15 (10.7%) high-risk patients died., Conclusion: Adherence to the febrile neutropenia guidelines was low resulting in unnecessary hospital admissions of low-risk patients and frequent over-prescription of empirical vancomycin.

Purpose: This study aimed to describe the care provide by Emergency Medical Services (EMS) to severe sepsis patients being transferred between acute care hospitals and identify how that care contributes to sepsis care goals., Methods: This was a single-center retrospective cohort study conducted at a 60,000-visit Midwestern academic emergency department, using run reports from 13 ambulance services transferring from 9 hospitals., Results: 39 patients were included in the final cohort, transferred by 13 ambulance services from 9 hospitals. Included patients were adults with severe sepsis transferred by ambulance between 2009 and 2014. Thirty-nine patients were included in this cohort. 41% (n = 12) of patients received an adequate fluid bolus of 30 mL/kg (median 42.9 mL/kg crystalloid fluid, IQR 8.0 mL/kg) prior to tertiary care arrival. Seventeen percent (n = 2) of patients completed the adequate bolus during transfer time. Broad-spectrum antibiotics were initiated during transfer in 2 patients., Conclusions: EMS sepsis care during transfer was limited. EMS crews primarily continued treatments previously initiated and did not take additional steps toward resuscitation targets. Data suggests the inter-emergency department transfer period may provide an opportunity to continue working toward treatment targets, though the time is currently underutilized., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: The incidence of patients who present with life-threatening bleeding complications has been increasing as the use of direct oral anticoagulation (DOAC) has increased. Therefore, effective reversal agents are urgently needed. Current guidelines recommend the use of prothrombin complex concentrates (PCCs) and activated PCCs (aPCC) for reversal of DOAC anticoagulant activity in the setting of traumatic and non-traumatic intracranial hemorrhage (ICH). However, little data is available., Objective: Herein, we investigated the safety and effectiveness of Factor Eight Inhibitor Bypassing Activity [FEIBA (an aPCC)] in a population of patients who required emergent reversal of DOAC for hemorrhage or urgent surgical interventions., Methods: This is a case series study. Medical records from patients who required emergent reversal of DOAC for life threatening hemorrhage or urgent surgical interventions were collected from February 1, 2014, to April 1, 2017 and reviewed. Data, including demographics as well as safety, outcomes, and dosing of FEIBA for reversal of DOAC effects were collected and descriptive statistics were obtained., Results: Forty-two patients who received FEIBA were included in the study. The rates of thrombotic events (10%), hemorrhage progression (10%), and observed mortality (29%) were similar to rates previously published in the limited literature evaluating aPCC use in this population., Conclusion: This case series suggests that FEIBA administration is relatively safe and effective to reverse DOACs in the setting of hemorrhage or need for urgent surgical procedures. Until target-specific reversal agents are available, future studies are warranted to evaluate the effectiveness of aPCC administration for DOAC-associated hemorrhagic complications., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Study Objective: The purpose of this study is to test the hypothesis that balanced crystalloids improve quality of recovery more than normal saline solution (0.9% sodium chloride) in stable emergency department (ED) patients. Secondary outcomes measured differences in health care use., Methods: A single-site, participant- and evaluator-blinded, 2-arm parallel allocation (1:1), comparative effectiveness, randomized controlled trial allocated adults receiving intravenous fluids in the ED before discharge to receive 2 L of lactated Ringer's solution or normal saline solution. The primary outcome was symptom scores measured by the validated Quality of Recovery-40 instrument (scores 40 to 200) 24 hours after enrollment. Secondary outcomes included subsequent health care use and medication compliance., Results: Participants (N=157) were enrolled and follow-up was analyzed for 94 (follow-up rate of 60%) with intention-to-treat methodology. There was no difference in postenrollment Quality of Recovery-40 scores between normal saline solution and lactated Ringer's solution groups (mean difference 2.4; 95% confidence interval [CI] -6.8 to 11.6). Although preenrollment scores were higher in the lactated Ringer's solution group (mean difference 10.5; 95% CI 1.9 to 19.0), adjusting for presurvey imbalances did not change the primary outcome (adjusted difference -3.9; 95% CI -12.9 to 5.2). There were no differences in return to ED (mean difference 7.5%; 95% CI -8.7% to 23.8%), prescriptions filled (mean difference 22.2%; 95% CI -3.3% to 47.6%), or seeking care from another provider (mean difference -2.0%; 95% CI -19.9% to 15.9%) at 7 days., Conclusion: Normal saline solution and lactated Ringer's solution were associated with similar 24-hour recovery scores and 7-day health care use in stable ED patients. These results supplement those of recent trials by informing fluid choice for stable ED patients., (Copyright © 2018 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Antimicrobial resistance remains a significant obstacle for clinicians when treating patients presenting to the emergency department (ED) with urinary tract infections., Objective: The goal of the proposed study was to validate a previously developed clinical decision rule identifying risk factors for multidrug-resistant (MDR) urinary pathogens., Methods: We conducted a validation study of a previously published clinical decision rule to identify patients with MDR urinary pathogens using a cohort from an urban academic center ED with annual census over 80 000. Using our previously identified clinical risk factors, we determined the sensitivity, specificity, positive likelihood ratio (+LR), and negative LR (-LR) to estimate measures of precision of our clinical decision rule in the validation cohort., Results: Factors associated with MDR urinary pathogen included sex, recent hospitalization, nursing home residency, and catheter placement. Using our previously defined threshold of greater than 1 risk factor, the adjusted model in the validation cohort identified that only nursing home residency was associated with positive MDR pathogen (adjusted odds ratio = 4.13; 95% CI = 1.95-8.77). The clinical decision rule in the validation cohort yielded a sensitivity of 56.4%, specificity of 66.3%, +LR of 1.7, and -LR of 0.7. Conclusion and Relevance: Our clinical decision rule to identify patients at risk for MDR urinary pathogens was unable to be validated in the setting of different antimicrobial resistance patterns. Future studies should evaluate an improved clinical decision rule identifying risk factors associated with MDR pathogens that performs well in varying patient populations.

Introduction: Intracranial hemorrhage (ICH) is a complication of warfarin-associated anticoagulation resulting in significant morbidity and mortality. The purpose of this study was to assess whether interhospital transfer delays the administration of 4-factor prothrombin complex concentrate to patients with warfarin-associated ICH., Materials and Methods: This was a retrospective cohort study of all patients presenting to a 60,000 visit academic ED between August 2013 and July 2017 requiring emergent anticoagulation reversal for warfarin-associated ICH. Patients were divided into 2 cohorts: (1) transfer patients who arrived at the academic center after receiving care in a local community hospital and (2) control patients who presented directly to the academic center ED. The primary outcome was time to administration of 4-factor prothrombin complex concentrate. Secondary outcomes included hematoma expansion, guideline-adherent vitamin K administration (10mg IV), intensive care unit and hospital length of stay, disposition at discharge, and in-hospital mortality., Results: This study included 203 patients (177 transfer patients, 26 control). The median time to arrival in transfer patients was 186 minutes (IQR 145-242). The median time to administration of guideline-adherent therapy in transfer patients was 296 minutes, compared to 119 minutes in patients who were not transferred (median difference= -176, 95% confidence interval -143 to -208, P ≤ .001). Delay in anticoagulation reversal did not result in hematoma expansion, intensive care unit and hospital length of stay, discharge disposition, or in-hospital mortality., Conclusions: Patients requiring interhospital transfer experienced significant delays in guideline-adherent anticoagulation reversal for warfarin-associated ICH, but this delay was not associated with worse outcomes., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Introduction: Rural and critical access hospitals rely on the "drip and ship" practice using helicopter emergency medical services (HEMS). But those helicopter flights are an unusual environment with physical factors such as vibration and accelerations that could potentially affect the stability, and pharmacological properties of IV rtPA, an issue that has not been previously addressed., Materials and Methods: This was a prospective cohort study of consecutive acute ischemic stroke patients receiving IV rtPA through a Comprehensive Stroke Center from November 2015 to February 2017 to measure the effects of HEMS on the integrity and activity of rtPA by collecting residual medication left in the vial., Clinical Trial Registration: http://www.clinicaltrials.gov. NCT02752256 RESULTS: A total of 33 patients and rtPA samples were included; 18 patients who presented directly to the Comprehensive Stroke Center emergency department and 15 patients who received rtPA during air ambulance transfer. The median rtPA antigen concentration in the residual medication vial was 3.04 mg/mL (IQR: 1.24-3.87) in the HEMS group and 1.91 mg/mL (IQR: 1.33-2.60) in the controls (P = .168). There were no significant differences in rtPA activity or specific activity between the HEMS and control groups and there was no association between total HEMS flight time on overall rtPA specific activity., Conclusions: In summary, this study provides supportive evidence of the lack of a detrimental effect of the HEMS physical environment on the integrity of rtPA, therefore endorsing current drip and ship practices without infusion adjustments., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Purpose: (1) To test whether serum bicarbonate or anion gap can be used to predict elevated lactate or mortality in emergency department (ED) patients with sepsis, and (2) to define thresholds that may predict elevated lactate and mortality., Methods: Retrospective diagnostic-validation study of adults with sepsis treated in a 60,000-visit Midwestern university ED (2010-2015). In the derivation sample, 8 experts selected thresholds based on objective measures to optimize clinical utility. Test performance was reported using likelihood ratios (LR +/-) in the validation cohort., Results: We included 4159 patients. Anion gap predicted lactate>2 better than bicarbonate [ROC AUC 0.680 vs. 0.609], and anion gap predicted lactate>4 better than lactate>2 [ROC AUC 0.816 vs. 0.680]. In the validation cohort, anion gap ≥20mEq/L had LR+ for lactate>2 of 3.670 (2.630-5.122), lactate>4 of 7.019 (5.310-9.278), and mortality of 2.768 (1.922-3.986). Anion gap predicted mortality similar to lactate>2 [LR+ 2.768 vs. LR+ 2.09; LR- 0.823 vs. 0.447]., Conclusions: Anion gap and serum bicarbonate poorly predict changes in lactate and mortality. In resource-limited settings where lactate is unavailable, anion gap ≥20mEq/L may be used to further risk-stratify patients for ongoing sepsis care, but lactate remains a preferred biomarker., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: Results of a study of anticoagulation reversal agent availability in rural and community hospital emergency departments (EDs) are reported., Methods: A cross-sectional telephone survey was conducted to test the hypothesis that anticoagulation reversal agents are not commonly stocked in low-volume EDs. In phase 1 of the study, a physician, pharmacist, or nurse manager at a sample of EDs in 1 state was surveyed to characterize anticoagulation reversal agent availability and the presence or absence of reversal protocols; in phase 2, follow-up qualitative interviews were conducted with hospital pharmacists selected by purposive sampling to identify barriers to availability., Results: Among the 103 EDs represented in the survey, 87 (84%) stocked fresh frozen plasma, 14 (14%) stocked 4-factor prothrombin complex concentrate (4F-PCC), and 2 (2%) stocked activated 4F-PCC. Forty-one EDs (40%) had a warfarin reversal protocol, but only 2 (2%) EDs had a protocol for direct oral anticoagulant reversal. ED volume and neurology coverage were significantly associated with reversal agent availability ( p = 0.014) and warfarin protocol availability ( p < 0.001). Identified factors contributing to reversal agent nonavailability were product cost, lack of knowledge of drug availability, and concerns about shelf life., Conclusion: An investigation of rural and community hospitals in 1 state revealed that the institutions rarely have specialized anticoagulation reversal drugs available. Cost and infrequency of utilization were 2 commonly cited reasons for reversal agent nonavailability., (Copyright © 2018 by the American Society of Health-System Pharmacists, Inc. All rights reserved.)

Introduction: Pneumonia impacts over four million people annually and is the leading cause of infectious disease-related hospitalization and mortality in the United States. Appropriate empiric antimicrobial therapy decreases hospital length of stay and improves mortality. The objective of our study was to test the hypothesis that the presence of an emergency medicine (EM) clinical pharmacist improves the timing and appropriateness of empiric antimicrobial therapy for community-acquired pneumonia (CAP) and healthcare-associated pneumonia (HCAP)., Methods: This was a retrospective observational cohort study of all emergency department (ED) patients presenting to a Midwest 60,000-visit academic ED from July 1, 2008, to March 1, 2016, who presented to the ED with pneumonia and received antimicrobial therapy. The treatment group consisted of patients who presented during the hours an EM pharmacist was present in the ED (Monday-Friday, 0900-1800). The control group included patients presenting during the hours when an EM clinical pharmacist was not physically present in the ED (Monday-Friday, 1800-0900, Saturday/Sunday 0000-2400 day). We defined appropriate empiric antimicrobial therapy using the Infectious Diseases Society of America consensus guidelines on the management of CAP, and management of HCAP., Results: A total of 406 patients were included in the final analysis (103 treatment patients and 303 control patients). During the hours the EM pharmacist was present, patients were significantly more likely to receive appropriate empiric antimicrobial therapy (58.3% vs. 38.3%; p<0.001). Regardless of pneumonia type, patients seen while an EM pharmacist was present were significantly more likely to receive appropriate antimicrobial therapy (CAP, 77.7% vs. 52.9% p=0.008, HCAP, 47.7% vs. 28.8%, p=0.005). There were no significant differences in clinical outcomes., Conclusion: The presence of an EM clinical pharmacist significantly increases the likelihood of appropriate empiric antimicrobial therapy for patients presenting to the ED with pneumonia., Competing Interests: Conflicts of Interest: By the WestJEM article submission agreement, all authors are required to disclose all affiliations, funding sources and financial or management relationships that could be perceived as potential sources of bias. This study was partially funded by a research grant from the American Society of Health-System Pharmacists (ASHP) Research and Education Foundation and the Department of Emergency Medicine at the University of Iowa, Iowa City, IA.

Objective: Telemedicine networks are beginning to provide an avenue for conducting emergency medicine research, but using telemedicine to recruit participants for clinical trials has not been validated. The goal of this consent study was to determine whether patient comprehension of telemedicine-enabled research informed consent is noninferior to standard face-to-face (F2F) research informed consent., Methods: A prospective, open-label randomized controlled trial was performed in a 60,000-visit Midwestern academic emergency department (ED) to test whether telemedicine-enabled research informed consent provided noninferior comprehension compared with standard consent. This study was conducted as part of a parent clinical trial evaluating the effectiveness of 0.12% oral chlorhexidine gluconate in preventing hospital-acquired pneumonia among adult ED patients with expected hospital admission. Prior to being recruited into the study, potential participants were randomized in a 1:1 allocation ratio to consent by telemedicine versus standard F2F consent. Telemedicine connectivity was provided using a commercially available interface (REACH platform, Vidyo Inc.) to an emergency physician located in another part of the ED. Comprehension of research consent (primary outcome) was measured using the modified quality of informed consent (QuIC) instrument, a validated tool for measuring research informed consent comprehension. Parent trial accrual rate and qualitative survey data were secondary outcomes., Results: A total of 131 patients were randomized (n = 64, telemedicine), and 101 QuIC surveys were completed. Comprehension of research informed consent using telemedicine was not inferior to F2F consent (QuIC scores 74.4 ± 8.1 vs. 74.4 ± 6.9 on a 100-point scale, p = 0.999). Subjective understanding of consent (p = 0.194) and parent trial study accrual rates (56% vs. 69%, p = 0.142) were similar., Conclusion: Telemedicine is noninferior to F2F consent for delivering research informed consent, with no detected differences in comprehension and patient-reported understanding. This consent study will inform design of future telemedicine-enabled clinical trials., (© 2016 by the Society for Academic Emergency Medicine.)

Objectives: The primary objective of this study was to evaluate potential interference of Trinder-based chemistry assays by N-acetylcysteine (NAC). A secondary objective was to look for evidence of interference in patients treated with NAC for acetaminophen (APAP) overdose., Design and Methods: Dilutions of NAC in plasma were tested for interference using the following Roche Diagnostics Trinder-based assays on a cobas 8000 system: enzymatic creatinine (Cr), cholesterol (CHOL), high-density lipoprotein cholesterol (HDL-C), triglycerides (TRIG), and uric acid (UA). Two non-Trinder Roche assays - urea nitrogen (BUN) and glucose (GLUC) - were tested as controls. Sekisui N-geneous® low-density lipoprotein cholesterol (LDL-C) reagent was also evaluated. Retrospective chart review of APAP overdose cases over 49months was conducted to look for differences in plasma Cr before and after intravenous (IV) NAC administration., Results: NAC concentrations (shown in parentheses) that caused ≥10% inhibition for individual assays were (in order of sensitivity to interference): TRIG (570mg/L)>CHOL (740mg/L)≈Cr (790mg/L)>UA (1100mg/L)>HDL-C (1760mg/L)>LDL-C (2900mg/L). Neither BUN nor GLUC achieved significant inhibition up to 10,000mg/L NAC. Evidence for relatively minor inhibition of Cr was observed in patients after NAC administration., Conclusions: NAC inhibition of the assays investigated typically occurs at concentrations higher than expected during IV and oral NAC therapy., (Copyright © 2015 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Objective: To test the hypothesis that interhospital transfer causes significant delays in the administration of appropriate antibiotics and compliance with the completion of Surviving Sepsis Bundle elements., Design: Single-center retrospective cohort study., Setting: A comprehensive 60,000-visit emergency department at a 711-bed Midwestern academic medical center., Patients: Patients with severe sepsis and septic shock treated between 2009 and 2014 were identified by International Classification of Diseases,9th Revision, Clinical Modification, codes, then divided into two cohorts: 1) transfer patients who arrived at the tertiary academic center after receiving care in a local community hospital and 2) control patients who presented directly to the tertiary academic center emergency department., Interventions: None., Measurement and Main Results: One hundred ninety-three patients were included. Transfer patients were more likely to require surgery in the hospital (p < 0.001) and require ICU care (p = 0.001) but had similar illness severity based on (Acute Physiology and Chronic Health Evaluation II, 17.7 vs 17.5; p = 0.662). Antibiotic administration at 1 and 3 hours was comparable between the two cohorts, but initial antibiotic appropriateness was lower in transfer patients (34% vs 79%; p < 0.001). Transfer patients were less likely to have fluid resuscitation started by 3 hours (54% vs 89%; p < 0.001), but they were not less likely to receive an adequate fluid bolus (30 mL/kg) by the time of hospital admission (p = 0.056). There were no differences in ICU length of stay or mortality., Conclusions: Interhospital transfer significantly delays administration of appropriate initial antibiotics and resuscitation therapy. Future studies are needed to identify strategies of providing regional sepsis care prior to transfer to tertiary centers and to continue care pathways during the interhospital transfer process.

Background: Identifying patients at high risk for multidrug-resistant urinary tract infections (UTIs) is important for guiding empirical antimicrobial therapy. Clinical risk factors associated with antimicrobial-resistant urinary pathogens and the derivation of a simple clinical decision rule could help define health care-associated UTI., Objective: To derive a simple clinical decision rule to identify clinical risk factors associated with antimicrobial-resistant urinary pathogens., Methods: This was a retrospective case-control study of all emergency department (ED) patients from July 1, 2011, to July 1, 2012, who presented to the ED with UTI and a positive urine culture. Candidate risk factors were collected retrospectively from medical record review. We compared differences in patient characteristics stratified by the presence of an antimicrobial-resistant urinary pathogen., Results: A total of 360 patients with UTI had a positive, noncontaminated urine culture during the study period. About 6.7% of patients (n = 24) had a multidrug-resistant (MDR) urinary infection. Logistic regression modeling identified 3 clinical factors associated with the identification of a MDR pathogen: male sex, chronic hemodialysis, and nursing home residence. A scoring system was created to identify patients with MDR pathogens. Test characteristics were calculated using bootstrapping for internal validation, with a sensitivity of 74.7% (95% CI = 55.1%-91.3%) and specificity of 85.1% (95% CI = 77.8%-86.2%), positive likelihood ratio of 4.3, and a negative likelihood ratio of 0.3., Conclusions: Clinical factors can be used to identify UTI patients at high risk of MDR urinary pathogens., (© The Author(s) 2015.)