Front-Line Emergency Department Clinician Acceptability and Use of a Prototype Real-Time Cloud-Based Influenza Surveillance System.

Objectives: To assess emergency department (ED) clinicians' perceptions of a novel real-time influenza surveillance system using a pre- and post-implementation structured survey. Methods: We created and implemented a laboratory-based real-time influenza surveillance system at two EDs at the beginning of the 2013-2014 influenza season. Patients with acute respiratory illness were tested for influenza using rapid PCR-based Cepheid Xpert Flu assay. Results were instantaneously uploaded to a cloud-based data aggregation system made available to clinicians via a web-based dashboard. Clinicians received bimonthly email updates summating year-to-date results. Clinicians were surveyed prior to, and after the influenza season, to assess their views regarding acceptability and utility of the surveillance system data which were shared via dashboard and email updates. Results: The pre-implementation survey revealed that the majority (82%) of the 151 ED clinicians responded that they "sporadically" or "don't," actively seek influenza-related information during the season. However, most (75%) reported that they would find additional information regarding influenza prevalence useful. Following implementation, there was an overall increase in the frequency of clinician self-reporting increased access to surveillance information from 50 to 63%, with the majority (75%) indicating that the surveillance emails impacted their general awareness of influenza. Clinicians reported that the additional real-time surveillance data impacted their testing (65%) and treatment (51%) practices. Conclusions: The majority of ED clinicians found surveillance data useful and indicated the additional information impacted their clinical practice. Accurate and timely surveillance information, distributed in a provider-friendly format could impact ED clinician management of patients with suspected influenza.

Intravenous peramivir vs oral oseltamivir in high-risk emergency department patients with influenza: Results from a pilot randomized controlled study.

BACKGROUND: Peramivir offers a single-dose intravenous (IV) treatment option for influenza (vs 5-day oral dosing for oseltamivir). We sought to compare outcomes of emergency department (ED) patients at high risk for influenza complications treated with IV peramivir vs oral oseltamivir. METHODS: During the 2015-16 and 2016-17 influenza seasons, adult patients in two US EDs were randomized to either oral oseltamivir or IV peramivir treatment group. Eligibility included positive molecular influenza test; met CDC criteria for antiviral treatment; able to provide informed consent and agree to follow-up assessment. Outcomes were measured by clinical end-point indicators, including FLU-PRO Score, Ordinal Scale, Patient Global Impression on Severity Score, and Karnofsky Performance Scale for 14 days. Non-inferior t test was performed to assess comparative outcomes between the two groups. RESULTS: Five hundred and seventy-five (68%) of 847 influenza-positive patients were approached. Two hundred and eighty-four met enrollment criteria and 179 were enrolled; of these 95 (53%) were randomized to peramivir, and 84 to oseltamivir. Average FLU-PRO score at baseline was similar (peramivir: 2.67 vs oseltamivir: 2.52); the score decreased over time for both groups (day 5: peramivir: 1.71 vs oseltamivir: 1.62; day 10: peramivir: 1.48 vs oseltamivir: 1.37; day 14: peramivir: 1.40 vs oseltamivir: 1.33; all P < .05 for significantly non-inferior). Influenza-related complications were similar between two groups (All: peramivir: 31% vs oseltamivir: 21%, P > .05; pneumonia: peramivir: 11% vs oseltamivir: 14%, P > .05). CONCLUSIONS: Clinical outcomes of influenza-infected patients treated with single-dose IV peramivir were comparable to those treated with oral oseltamivir, suggesting potential utility of peramivir for influenza-infected patients in the ED.

Derivation and Validation of a Clinical Decision Guideline for Influenza Testing in 4 US Emergency Departments.

BACKGROUND: An accurate diagnosis of influenza is essential for appropriate antiviral treatment, in accordance with Centers for Disease Control and Prevention (CDC) guidelines. However, no clear guidance exists on which patients should be tested. We sought to develop a clinical decision guideline (CDG) to inform influenza testing decisions for those adult emergency department (ED) patients deemed appropriate for antiviral treatment by CDC guidelines. METHODS: A prospective cohort study was performed at 4 US EDs. From November 2013 to April 2014, we enrolled adult ED patients with fever or respiratory symptoms who met criteria for antiviral treatment, per 2013 CDC guidelines. All patients were tested for influenza using polymerase chain reaction. Data were randomly split into derivation (80%) and validation (20%) data sets. A discrete set of independent variables was selected by logistic regression, using the derivation set to create a scoring system, with a target sensitivity of at least 90%. The derived CDG was then validated. RESULTS: Of 1941 enrolled participants, 183 (9.4%) had influenza. The derived CDG included new or increased cough (2 points), headache (1 point), subjective fever (1 point), and triage temperature >100.4°C (1 point), with a score of ≥3 indicating influenza testing was warranted. The CDG had a sensitivity and specificity of 94.1% and 36.6%, respectively, in the derivation set and of 91.5% and 34.6%, respectively, in the validation set. CONCLUSIONS: A CDG with high sensitivity was derived and validated. Incorporation into practice could standardize testing for high-risk patients in adult EDs during influenza seasons, potentially improving diagnoses and treatment. CLINICAL TRIAL REGISTRATION: NCT01947049.

Clinical Development of Therapeutic Agents for Hospitalized Patients With Influenza: Challenges and Innovations.

BACKGROUND: Since 1999, the US Food and Drug Administration approved neuraminidase and endonuclease inhibitors to treat uncomplicated outpatient influenza but not severe hospitalized influenza. After the 2009 pandemic, several influenza hospital-based clinical therapeutic trials were unsuccessful, possibly due to certain study factors. Therefore, in 2014, the US Health and Human Services agencies formed a Working Group (WG) to address related clinical challenges. METHODS: Starting in 2014, the WG obtained retrospective data from failed hospital-based influenza therapeutic trials and nontherapeutic hospital-based influenza studies. These data allowed the WG to identify factors that might improve hospital-based therapeutic trials. These included primary clinical endpoints, increased clinical site enrollment, and appropriate baseline enrollment criteria. RESULTS: During 2018, the WG received retrospective data from a National Institutes of Health hospital-based influenza therapeutic trial that demonstrated time to resolution of respiratory status, which was not a satisfactory primary endpoint. The WG statisticians examined these data and believed that ordinal outcomes might be a more powerful primary endpoint. Johns Hopkins' researchers provided WG data from an emergency-department (ED) triage study to identify patients with confirmed influenza using molecular testing. During the 2013-2014 influenza season, 4 EDs identified 1074 influenza-patients, which suggested that triage testing should increase enrollment by hospital-based clinical trial sites. In 2017, the WG received data from Northwestern Memorial Hospital researchers regarding 703 influenza inpatients over 5 seasons. The WG applied National Early Warning Score (NEWS) at patient baseline to identify appropriate criteria to enroll patients into hospital-based therapeutic trials. CONCLUSIONS: Data received by the WG indicated that hospital-based influenza therapeutic trials could use ordinal outcome analyses, ED triage to identify influenza patients, and NEWS for enrollment criteria.

Use of a Rapid Diagnostic for Chlamydia trachomatis and Neisseria gonorrhoeae for Women in the Emergency Department Can Improve Clinical Management: Report of a Randomized Clinical Trial.

STUDY OBJECTIVE: In emergency departments (EDs), diagnosis and treatment of Chlamydia trachomatis and Neisseria gonorrhoeae are challenging. We conducted a randomized clinical trial to assess rapid C trachomatis and N gonorrhoeae testing on overtreatment and undertreatment of women evaluated for C trachomatis and N gonorrhoeae. METHODS: Women undergoing pelvic examinations and C trachomatis and N gonorrhoeae testing (n=254) were randomized to control or rapid test groups. The control group received standard-of-care C trachomatis and N gonorrhoeae nucleic acid amplification tests of endocervical specimens, with 2- to 3-day turnaround times. For the rapid test group, clinicians collected an extra endocervical swab for GeneXpert C trachomatis and N gonorrhoeae rapid testing, in addition to the standard-of-care nucleic acid amplification test swab. Rapid results were immediately provided, and all patients were treated according to providers' clinical judgment. RESULTS: In the rapid test group, 7.9% of patients had positive test results for C trachomatis; 3.9% had positive test results for N gonorrhoeae. In the control standard-of-care group, 10.2% of patients had positive nucleic acid amplification test results for C trachomatis; 5.5% had positive results for N gonorrhoeae. Undertreatment for both C trachomatis and N gonorrhoeae in the ED was 0% for the rapid test group and 43.8% for the control standard-of-care group. Clinicians overtreated 46.5% of uninfected standard-of-care control patients for C trachomatis compared with 23.1% of uninfected rapid test patients. For patients uninfected with N gonorrhoeae, clinicians overtreated 46.7% of standard-of-care control patients compared with 25.4% of rapid test patients. The length of stay did not differ significantly between groups. CONCLUSION: Rapid C trachomatis and N gonorrhoeae testing in the ED led to a significant reduction in overtreatment for women without infections compared with the standard-of-care control group. Additionally, in the rapid test group there was significant improvement in appropriate treatment for patients with infections.

Changing epidemiology and management of infectious diseases in US EDs.

BACKGROUND: The rise of antibiotic-resistant pathogens is believed to have influenced the emergency department (ED) epidemiology and management of infectious diseases (IDs) since 2000. METHODS: Data from the National Hospital Ambulatory Medical Care Survey from 2000 to 2010 were used to examine temporal trends in the incidence of IDs presenting to EDs. Outcome measures included national visit rates, visit proportions, and antimicrobial prescriptions for all ID primary diagnoses, as well as for specific organ systems of interest (respiratory tract, skin/soft tissue, and urinary tract). RESULTS: An ID-related primary diagnosis was given in 18.3% (95% confidence interval, 17.9%-18.8%) of all ED visits during the study period. The hospitalization rate for these conditions is 7.8% (95% confidence interval, 7.3%-8.3%). The share of macrolide prescriptions for upper respiratory tract infections and lower respiratory tract infections increased by 34% and 46%, respectively, and that of quinolone prescription for lower respiratory tract infections doubled from 9% to 18.4% during the study period. Management of skin and soft tissue infections shifted from predominant use of cephalosporins to sulfonamides. For UTIs, quinolones were most commonly prescribed, with an increasing use of third-generation cephalosporins. Antibiotics were more frequently prescribed to patients who are white compared with (white: 60%, black: 57%, other races: 52%, P < .05). CONCLUSION: The changing epidemiology of IDs diagnosed in US EDs reflects national trends in emerging pathogens and drug resistance. Broad-spectrum antibiotics are being prescribed at increasing rates. There are significant demographic disparities in nationwide antibiotic prescription practices.

A Randomized Clinical Trial Comparing Use of Rapid Molecular Testing for Staphylococcus aureus for Patients With Cutaneous Abscesses in the Emergency Department With Standard of Care.

OBJECTIVE: To determine whether real-time availability of rapid molecular results of Staphylococcus aureus would impact emergency department clinician antimicrobial selection for adults with cutaneous abscesses. DESIGN: We performed a prospective, randomized controlled trial comparing a rapid molecular test with standard of care culture-based testing. Follow-up telephone calls were made at between 2 and 7 days, 1 month, and 3 months after discharge. SETTING: Two urban, academic emergency departments. PATIENTS: Patients at least 18 years old presenting with a chief complaint of abscess, cellulitis, or insect bite and receiving incision and drainage were eligible. Seven hundred seventy-eight people were assessed for eligibility and 252 met eligibility criteria. METHODS: Clinician antibiotic selection and clinical outcomes were evaluated. An ad hoc outcome of test performance was performed. RESULTS: We enrolled 252 patients and 126 were randomized to receive the rapid test. Methicillin-susceptible S. aureus-positive patients receiving rapid test results were prescribed beta-lactams more often than controls (absolute difference, 14.5% [95% CI, 1.1%-30.1%]) whereas methicillin-resistant S. aureus-positive patients receiving rapid test results were more often prescribed anti-methicillin-resistant S. aureus antibiotics (absolute difference, 21.5% [95% CI, 10.1%-33.0%]). There were no significant differences between the 2 groups in 1-week or 3-month clinical outcomes. CONCLUSION: Availability of rapid molecular test results after incision and drainage was associated with more-targeted antibiotic selection. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01523899.

Clinical diagnosis of influenza in the ED.

BACKGROUND: Timely and accurate diagnosis of influenza remains a challenge but is critical for patients who may benefit from antiviral therapy. This study determined the test characteristics of provider diagnosis of influenza, final ED electronic medical record (EMR) diagnosis of influenza, and influenza-like illness (ILI) in patients recommended to receive antiviral treatment according to Centers for Disease Control and Prevention (CDC) guidelines. In addition, we evaluated the compliance with CDC antiviral guidelines. METHODS: A prospective cohort of adults presenting to a tertiary care ED with an acute respiratory illness who met CDC criteria for recommended antiviral treatment were enrolled and tested for influenza. A clinical diagnosis of influenza was assessed by asking the clinician: "Do you think this patient has influenza?" Influenza-like illness was defined according to current CDC criteria. RESULTS: In this cohort of 270 subjects, 42 (16%; 95% confidence interval [CI], 11%-20%) had influenza. Clinician diagnosis had a sensitivity of 36% (95% CI, 22%-52%) and specificity of 78% (95% CI, 72%-83%); EMR final ED diagnosis had a sensitivity of 26% (95% CI, 14%-42%) and specificity of 97% (95% CI, 94%-99%); ILI had a sensitivity of 31% (95% CI, 18%-47%) and specificity of 88% (95% CI, 83%-92%). Only 15 influenza-positive patients (36%) received antiviral treatment. CONCLUSION: Clinician diagnosis, final ED EMR diagnosis, and ILI have low sensitivity for diagnosing influenza, and there is overall poor compliance with CDC antiviral treatment recommendations. Improved methods of influenza diagnosis are needed to help guide management in the clinical setting.

Evaluation of the Xpert Flu rapid PCR assay in high-risk emergency department patients.

We prospectively evaluated the performance of Cepheid's GeneXpert Xpert Flu assay in a target population of 281 adults presenting to the emergency department with an acute respiratory illness who met Centers for Disease Control and Prevention (CDC) criteria for recommended antiviral treatment. Compared with the Prodesse ProFlu+ assay, Xpert Flu had an overall sensitivity of 95.3% and specificity of 99.2%.

Septic shock and adequacy of early empiric antibiotics in the emergency department.

BACKGROUND: Antibiotic resistance is an increasing concern for Emergency Physicians. OBJECTIVES: To examine whether empiric antibiotic therapy achieved appropriate antimicrobial coverage in emergency department (ED) septic shock patients and evaluate reasons for inadequate coverage. METHODS: Retrospective review was performed of all adult septic shock patients presenting to the ED of a tertiary care center from December 2007 to September 2008. Inclusion criteria were: 1) Suspected or confirmed infection; 2) ≥ 2 Systemic Inflammatory Response Syndrome criteria; 3) Treatment with one antimicrobial agent; 4) Hypotension requiring vasopressors. Patients were dichotomized by presentation from a community or health care setting. RESULTS: Eighty-five patients with septic shock were identified. The average age was 68 ± 15.8 years. Forty-seven (55.3%) patients presented from a health care setting. Pneumonia was the predominant clinically suspected infection (n = 38, 45%), followed by urinary tract (n = 16, 19%), intra-abdominal (n = 13, 15%), and other infections (n = 18, 21%). Thirty-nine patients (46%) had an organism identified by positive culture, of which initial empiric antibiotic therapy administered in the ED adequately covered the infectious organism in 35 (90%). The 4 patients who received inadequate therapy all had urinary tract infections (UTI) and were from a health care setting. CONCLUSION: In this population of ED patients with septic shock, empiric antibiotic coverage was inadequate in a small group of uroseptic patients with recent health care exposure. Current guidelines for UTI treatment do not consider health care setting exposure. A larger, prospective study is needed to further define this risk category and determine optimal empiric antibiotic therapy for patients.

Emergency Physicians' Adherence to Center for Disease Control and Prevention Guidance During the 2009 Influenza A H1N1 Pandemic.

INTRODUCTION: Little is known regarding compliance with management guidelines for epidemic influenza in adult emergency department (ED) settings during the 2009 novel influenza A (H1N1) epidemic, especially in relation to the Centers for Disease Control and Prevention (CDC) guidance. METHODS: We investigated all patients with a clinical diagnosis of influenza at an inner-city tertiary academic adult ED with an annual census of approximately 60,000 visits from May 2008 to December 2009. We aimed to determine patterns of presentation and management for adult patients with an ED diagnosis of influenza during the H1N1 pandemic, using seasonal influenza (pre-H1N1) as reference and to determine the ED provider's adherence to American College of Emergency Physicians and CDC guidance during the 2009 H1N1 influenza pandemic. Adherence to key elements of CDC 2009 H1N1 guidance was defined as (1) the proportion of admitted patients who were recommended to receive testing or treatment who actually received testing for influenza or treatment with antivirals; and (2) the proportion of high-risk patients who were supposed to be treated who actually were treated with antivirals. RESULTS: Among 339 patients with clinically diagnosed influenza, 88% occurred during the H1N1 pandemic. Patients were similarly managed during both phases. Median length of visit (pre-H1N1: 385 min, H1N1: 355 min, P > 0.05) and admission rates (pre-H1N1: 8%, H1N1: 11%, P > 0.05) were similar between the 2 groups. 28% of patients in the pre-H1N1 group and 16% of patients in the H1N1 group were prescribed antibiotics during their ED visits (P > 0.05). There were 34 admitted patients during the pandemic;, 30 (88%) of them received influenza testing in the ED, and 22 (65%) were prescribed antivirals in the ED. Noticeably, 19 (56%) of the 34 admitted patients, including 6 with a positive influenza test, received antibiotic treatment during their ED stay. CONCLUSION: During the recent H1N1 pandemic, most admitted patients received ED diagnostic testing corresponding to the current recommended guidance. Antibiotic treatment for ED patients admitted with suspected influenza is not uncommon. However, less than 70% of admitted patients and less than 50% of high-risk patients were treated with antivirals during their ED visit, indicating a specific call for closer adherence to guidelines in future influenza pandemics.

Diagnosis of spinal cord compression in nontrauma patients in the emergency department.

OBJECTIVES: The objectives were to evaluate the presenting signs and symptoms of spinal cord and cauda equina compression (SCC) and to determine the incidence of emergency department (ED) misdiagnosis. METHODS: This was a retrospective chart review at an urban, tertiary care hospital of patients discharged from an inpatient stay (April 2008 through July 2009) with an International Classification of Diseases, Ninth Revision (ICD-9) code indicating spinal disease, who had visited the ED for a related complaint within the previous 30 days, and who had a final diagnosis of new SCC. Trauma and transferred patients were excluded. The authors defined a misdiagnosis as no ED-documented diagnosis of SCC and failure to perform an appropriate diagnostic study either prior to arrival, in the ED, or immediately upon admission. RESULTS: Of 1,231 charts reviewed, 63 met inclusion criteria. The most common presenting symptoms in patients with SCC were pain (44, 70%), difficulty ambulating (38, 60%), and weakness (35, 56%). On physical examination, motor deficits (45, 71%) were more common than sensory deficits (27, 43%); however, 15 (24%) patients had no motor or sensory deficit, and 13 (23%) patients only had unilateral findings. Impaired gait was present in 14 patients of only 20 tested, three of whom had no associated motor or sensory deficit. SCC was misdiagnosed in 18 (29%, 95% confidence interval [CI] = 19% to 41%) cases, which resulted in a significant delay to diagnosis (median = 54 hours, interquartile range [IQR] = 38 to 77 vs. 5.3 hours, IQR = 3.0 to 15) in these patients. CONCLUSIONS: SCC can have a subtle presentation with absent or unilateral motor and sensory deficits, but gait ataxia may be an additional finding. ED misdiagnosis of SCC in nontrauma patients is common.