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.

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.

Reliability, Validity, and Responsiveness of InFLUenza Patient-Reported Outcome (FLU-PRO©) Scores in Influenza-Positive Patients.

OBJECTIVES: To assess the reliability, validity, and responsiveness of InFLUenza Patient-Reported Outcome (FLU-PRO©) scores for quantifying the presence and severity of influenza symptoms. METHODS: An observational prospective cohort study of adults (≥18 years) with influenza-like illness in the United States, the United Kingdom, Mexico, and South America was conducted. Participants completed the 37-item draft FLU-PRO daily for up to 14 days. Item-level and factor analyses were used to remove items and determine factor structure. Reliability of the final tool was estimated using Cronbach α and intraclass correlation coefficients (2-day reliability). Convergent and known-groups validity and responsiveness were assessed using global assessments of influenza severity and return to usual health. RESULTS: Of the 536 patients enrolled, 221 influenza-positive subjects comprised the analytical sample. The mean age of the patients was 40.7 years, 60.2% were women, and 59.7% were white. The final 32-item measure has six factors/domains (nose, throat, eyes, chest/respiratory, gastrointestinal, and body/systemic), with a higher order factor representing symptom severity overall (comparative fit index = 0.92; root mean square error of approximation = 0.06). Cronbach α was high (total = 0.92; domain range = 0.71-0.87); test-retest reliability (intraclass correlation coefficient, day 1-day 2) was 0.83 for total scores and 0.57 to 0.79 for domains. Day 1 FLU-PRO domain and total scores were moderately to highly correlated (≥0.30) with Patient Global Rating of Flu Severity (except nose and throat). Consistent with known-groups validity, scores differentiated severity groups on the basis of global rating (total: F = 57.2, P < 0.001; domains: F = 8.9-67.5, P < 0.001). Subjects reporting return to usual health showed significantly greater (P < 0.05) FLU-PRO score improvement by day 7 than did those who did not, suggesting score responsiveness. CONCLUSIONS: Results suggest that FLU-PRO scores are reliable, valid, and responsive to change in influenza-positive adults.

Machine-Learning-Based Electronic Triage More Accurately Differentiates Patients With Respect to Clinical Outcomes Compared With the Emergency Severity Index.

STUDY OBJECTIVE: Standards for emergency department (ED) triage in the United States rely heavily on subjective assessment and are limited in their ability to risk-stratify patients. This study seeks to evaluate an electronic triage system (e-triage) based on machine learning that predicts likelihood of acute outcomes enabling improved patient differentiation. METHODS: A multisite, retrospective, cross-sectional study of 172,726 ED visits from urban and community EDs was conducted. E-triage is composed of a random forest model applied to triage data (vital signs, chief complaint, and active medical history) that predicts the need for critical care, an emergency procedure, and inpatient hospitalization in parallel and translates risk to triage level designations. Predicted outcomes and secondary outcomes of elevated troponin and lactate levels were evaluated and compared with the Emergency Severity Index (ESI). RESULTS: E-triage predictions had an area under the curve ranging from 0.73 to 0.92 and demonstrated equivalent or improved identification of clinical patient outcomes compared with ESI at both EDs. E-triage provided rationale for risk-based differentiation of the more than 65% of ED visits triaged to ESI level 3. Matching the ESI patient distribution for comparisons, e-triage identified more than 10% (14,326 patients) of ESI level 3 patients requiring up triage who had substantially increased risk of critical care or emergency procedure (1.7% ESI level 3 versus 6.2% up triaged) and hospitalization (18.9% versus 45.4%) across EDs. CONCLUSION: E-triage more accurately classifies ESI level 3 patients and highlights opportunities to use predictive analytics to support triage decisionmaking. Further prospective validation is needed.

Geolocalization of Influenza Outbreak Within an Acute Care Population: A Layered-Surveillance Approach.

STUDY OBJECTIVE: We seek to use a novel layered-surveillance approach to localize influenza clusters within an acute care population. The first layer of this system is a syndromic surveillance screen to guide rapid polymerase chain reaction testing. The second layer is geolocalization and cluster analysis of these patients. We posit that any identified clusters could represent at-risk populations who could serve as high-yield targets for preventive medical interventions. METHODS: This was a prospective observational surveillance study. Patients were screened with a previously derived clinical decision guideline that has a 90% sensitivity and 30% specificity for influenza. Patients received points for the following signs and symptoms within the past 7 days: cough (2 points), headache (1 point), subjective fever (1 point), and documented fever at triage (temperature >38°C [100.4°F]) (1 point). Patients scoring 3 points or higher were indicated for influenza testing. Patients were tested with Xpert Flu (Cepheid, Sunnyvale, CA), a rapid polymerase chain reaction test. Positive results were mapped with ArcGIS (ESRI, Redlands, CA) and analyzed with kernel density estimation to create heat maps. RESULTS: There were 1,360 patients tested with Xpert Flu with retrievable addresses within the greater Phoenix metro area. One hundred sixty-seven (12%) of them tested positive for influenza A and 23 (2%) tested positive for influenza B. The influenza A virus exhibited a clear cluster pattern within this patient population. The densest cluster was located in an approximately 1-square-mile region southeast of our hospital. CONCLUSION: Our layered-surveillance approach was effective in localizing a cluster of influenza A outbreak. This region may house a high-yield target population for public health intervention. Further collaborative efforts will be made between our hospital and the Maricopa County Department of Public Health to perform a series of community vaccination events before the next influenza season. We hope these efforts will ultimately serve to reduce the burden of this disease on our patient population, and that this system will serve as a framework for future investigations locating at-risk populations.

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.

Google Flu Trends Spatial Variability Validated Against Emergency Department Influenza-Related Visits.

BACKGROUND: Influenza is a deadly and costly public health problem. Variations in its seasonal patterns cause dangerous surges in emergency department (ED) patient volume. Google Flu Trends (GFT) can provide faster influenza surveillance information than traditional CDC methods, potentially leading to improved public health preparedness. GFT has been found to correlate well with reported influenza and to improve influenza prediction models. However, previous validation studies have focused on isolated clinical locations. OBJECTIVE: The purpose of the study was to measure GFT surveillance effectiveness by correlating GFT with influenza-related ED visits in 19 US cities across seven influenza seasons, and to explore which city characteristics lead to better or worse GFT effectiveness. METHODS: Using Healthcare Cost and Utilization Project data, we collected weekly counts of ED visits for all patients with diagnosis (International Statistical Classification of Diseases 9) codes for influenza-related visits from 2005-2011 in 19 different US cities. We measured the correlation between weekly volume of GFT searches and influenza-related ED visits (ie, GFT ED surveillance effectiveness) per city. We evaluated the relationship between 15 publically available city indicators (11 sociodemographic, two health care utilization, and two climate) and GFT surveillance effectiveness using univariate linear regression. RESULTS: Correlation between city-level GFT and influenza-related ED visits had a median of .84, ranging from .67 to .93 across 19 cities. Temporal variability was observed, with median correlation ranging from .78 in 2009 to .94 in 2005. City indicators significantly associated (P<.10) with improved GFT surveillance include higher proportion of female population, higher proportion with Medicare coverage, higher ED visits per capita, and lower socioeconomic status. CONCLUSIONS: GFT is strongly correlated with ED influenza-related visits at the city level, but unexplained variation over geographic location and time limits its utility as standalone surveillance. GFT is likely most useful as an early signal used in conjunction with other more comprehensive surveillance techniques. City indicators associated with improved GFT surveillance provide some insight into the variability of GFT effectiveness. For example, populations with lower socioeconomic status may have a greater tendency to initially turn to the Internet for health questions, thus leading to increased GFT effectiveness. GFT has the potential to provide valuable information to ED providers for patient care and to administrators for ED surge preparedness.

An Electronic Emergency Triage System to Improve Patient Distribution by Critical Outcomes.

BACKGROUND: Patient triage is necessary to manage excessive patient volumes and identify those with critical conditions. The most common triage system used today, Emergency Severity Index (ESI), focuses on resources utilized and critical outcomes. OBJECTIVE: This study derives and validates a computer-based electronic triage system (ETS) to improve patient acuity distribution based on serious patient outcomes. METHODS: This cross-sectional study of 25,198 (97 million weighted) adult emergency department visits from the 2009 National Hospital Ambulatory Medical Care Survey. The ETS distributes patients by using a composite outcome based on the estimated probability of mortality, intensive care unit admission, or transfer to operating room or catheterization suite. We compared the ETS with the ESI based on the differentiation of patients, outcomes, inpatient hospitalization, and resource utilization. RESULTS: Of the patients included, 3.3% had the composite outcome and 14% were admitted, and 2.52 resources/patient were used. Of the 90% triaged to low-acuity levels, ETS distributed patients evenly (Level 3: 30%; Level 4: 30%, and Level 5: 29%) compared to ESI (46%, 34%, and 7%, respectively). The ETS better-identified patients with the composite outcome present in 40% of ETS Level 1 vs. 17% for ESI and the ETS area under the receiver operating characteristic curve (AUC) was 0.83 vs. ESI 0.73. Similar results were found for hospital admission (ETS AUC = 0.83 vs. ESI AUC = 0.72). The ETS demonstrated slight improvements in discriminating patient resource utilization. CONCLUSIONS: The ETS is a triage system based on the frequency of critical outcomes that demonstrate improved differentiation of patients compared to the current standard ESI.

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.

Cost-utility of rapid polymerase chain reaction-based influenza testing for high-risk emergency department patients.

STUDY OBJECTIVE: We evaluate the cost-effectiveness of polymerase chain reaction (PCR)-based rapid influenza testing and treatment for influenza in adult emergency department (ED) patients who are at high risk for or have evidence of influenza-related complications. METHODS: We developed a cost-utility decision analysis model that assessed adult patients presenting to the ED with symptoms of an acute respiratory infection, who met the Centers for Disease Control and Prevention criteria for recommended antiviral treatment. Analysis was performed from the societal perspective, with incremental comparisons of 4 influenza testing and treatment strategies: treat none, treat according to provider judgment, treat according to results of a PCR-based rapid diagnostic test, and treat all. RESULTS: Treating no patients with antivirals was dominated by all other strategies that increased in both cost and benefit in the following order: treat according to provider judgment, treat according to results of a PCR-based rapid diagnostic test, and treat all. As influenza prevalence increases, treating all patients eventually dominated all other options. CONCLUSION: The economic benefit of incorporating use of rapid PCR-based influenza testing for ED patients at risk of developing influenza-related complications depends on influenza prevalence; treatment guided by physician diagnosis or rapid testing, and treatment of all patients is more effective and less costly than no treatment.

Revitalizing a vital sign: improving detection of tachypnea at primary triage.

STUDY OBJECTIVE: This study evaluates the accuracy of emergency department (ED) triage respiratory rate measurement using the usual care method and a new electronic respiratory rate sensor (BioHarness, Zephyr Technology Corp.), both compared to a criterion standard measurement. METHODS: This is a cross-sectional study with convenience sampling conducted in an urban academic adult ED, including 3 separate respiratory rate measurements performed at ED triage: usual care measurement, electronic BioHarness measurement, and criterion standard measurement. The criterion standard measurement used was defined by the World Health Organization as manual observation or auscultation of respirations for 60 seconds. The resultant usual care and BioHarness measurements were compared with the criterion standard, evaluating accuracy (sensitivity and specificity) for detecting tachypnea, as well as potential systematic biases of usual care and BioHarness measurements using a Bland Altman analysis. RESULTS: Of 191 analyzed patients, 44 presented with tachypnea (>20 breaths/min). Relative to criterion standard measurement, usual care measurement had a sensitivity of 23% (95% confidence interval [CI] 12% to 37%) and specificity of 99% (95% CI 97% to 100%) for tachypnea, whereas BioHarness had a sensitivity of 91% (95% CI 80% to 97%) and specificity of 97% (95% CI 93% to 99%) for tachypnea. Usual care measurements clustered around respiratory rates of 16 and 18 breaths/min (n=144), with poor agreement with criterion standard measurement. Conversely, BioHarness measurement closely tracked criterion standard values over the range of respiratory rates. CONCLUSION: Current methods of respiratory rate measurement at ED triage are inaccurate. A new electronic respiratory rate sensor, BioHarness, has significantly greater sensitivity for detecting tachypnea versus usual care method of measurement.

Google Flu Trends: correlation with emergency department influenza rates and crowding metrics.

BACKGROUND: Google Flu Trends (GFT) is a novel Internet-based influenza surveillance system that uses search engine query data to estimate influenza activity and is available in near real time. This study assesses the temporal correlation of city GFT data to cases of influenza and standard crowding indices from an inner-city emergency department (ED). METHODS: This study was performed during a 21-month period (from January 2009 through October 2010) at an urban academic hospital with physically and administratively separate adult and pediatric EDs. We collected weekly data from GFT for Baltimore, Maryland; ED Centers for Disease Control and Prevention-reported standardized influenzalike illness (ILI) data; laboratory-confirmed influenza data; and ED crowding indices (patient volume, number of patients who left without being seen, waiting room time, and length of stay for admitted and discharged patients). Pediatric and adult data were analyzed separately using cross-correlation with GFT. RESULTS: GFT correlated with both number of positive influenza test results (adult ED, r = 0.876; pediatric ED, r = 0.718) and number of ED patients presenting with ILI (adult ED, r = 0.885; pediatric ED, r = 0.652). Pediatric but not adult crowding measures, such as total ED volume (r = 0.649) and leaving without being seen (r = 0.641), also had good correlation with GFT. Adult crowding measures for low-acuity patients, such as waiting room time (r = 0.421) and length of stay for discharged patients (r = 0.548), had moderate correlation with GFT. CONCLUSIONS: City-level GFT shows strong correlation with influenza cases and ED ILI visits, validating its use as an ED surveillance tool. GFT correlated with several pediatric ED crowding measures and those for low-acuity adult patients.

Viral co-infections are associated with increased rates of hospitalization in those with influenza.

BACKGROUND: Influenza causes significant morbidity and mortality in the United States. Among patients infected with influenza, the presence of bacterial co-infection is associated with worse clinical outcomes; less is known regarding the clinical importance of viral co-infections. The objective of this study was to determine rates of viral co-infections in emergency department (ED) patients with confirmed influenza and association of co-infection with disease severity. METHODS: Secondary analysis of a biorepository and clinical database from a parent study where rapid influenza testing was implemented in four U.S. academic EDs, during the 2014-2015 influenza season. Patients were systematically tested for influenza virus using a validated clinical decision guideline. Demographic and clinical data were extracted from medical records; nasopharyngeal specimens from influenza-positive patients were tested for viral co-infections (ePlex, Genmark Diagnostics). Patterns of viral co-infections were evaluated using chi-square analysis. The association of viral co-infection with hospital admission was assessed using univariate and multivariate regression. RESULTS: The overall influenza A/B positivity rate was 18.1% (1071/5919). Of the 999 samples with ePlex results, the prevalence of viral co-infections was 7.9% (79/999). The most common viral co-infection was rhinovirus/enterovirus (RhV/EV), at 3.9% (39/999). The odds of hospital admission (OR 2.33, 95% CI: 1.01-5.34) increased significantly for those with viral co-infections (other than RhV/EV) versus those with influenza A infection only. CONCLUSION: Presence of viral co-infection (other than RhV/EV) in ED influenza A/B positive patients was independently associated with increased risk of hospital admission. Further research is needed to determine clinical utility of ED multiplex testing.

Cloud-Based Influenza Surveillance System in Emergency Departments Using Molecular-Based Testing: Advances and Challenges.

INTRODUCTION: Electronic influenza surveillance systems aid in health surveillance and clinical decision-making within the emergency department (ED). While major advances have been made in integrating clinical decision-making tools within the electronic health record (EHR), tools for sharing surveillance data are often piecemeal, with the need for data downloads and manual uploads to shared servers, delaying time from data acquisition to end-user. Real-time surveillance can help both clinicians and public health professionals recognize circulating influenza earlier in the season and provide ongoing situational awareness. METHODS: We created a prototype, cloud-based, real-time reporting system in two large, academically affiliated EDs that streamed continuous data on a web-based dashboard within hours of specimen collection during the influenza season. Data included influenza test results (positive or negative) coupled with test date, test instrument geolocation, and basic patient demographics. The system provided immediate reporting to frontline clinicians and to local, state, and federal health department partners. RESULTS: We describe the process, infrastructure requirements, and challenges of developing and implementing the prototype system. Key process-related requirements for system development included merging data from the molecular test (GeneXpert) with the hospitals' EHRs, securing data, authorizing/authenticating users, and providing permissions for data access refining visualizations for end-users. CONCLUSION: In this case study, we effectively integrated multiple data systems at four distinct hospital EDs, relaying data in near real time to hospital-based staff and local and national public health entities, to provide laboratory-confirmed influenza test results during the 2014-2015 influenza season. Future innovations need to focus on integrating the dashboard within the EHR and clinical decision tools.

Impact of coinfection status and comorbidity on disease severity in adult emergency department patients with influenza B.

BACKGROUND: Influenza B accounts for approximately one fourth of the seasonal influenza burden. However, research on the importance of influenza B has received less attention compared to influenza A. We sought to describe the association of both coinfections and comorbidities with disease severity among adults presenting to emergency departments (ED) with influenza B. METHODS: Nasopharyngeal samples from patients found to be influenza B positive in four US and three Taiwanese ED over four consecutive influenza seasons (2014-2018) were tested for coinfections with the ePlex RP RUO panel. Multivariable logistic regressions were fitted to model adjusted odds ratios (aOR) for two severity outcomes separately: hospitalization and pneumonia diagnosis. Adjusting for demographic factors, underlying health conditions, and the National Early Warning Score (NEWS), we estimated the association of upper respiratory coinfections and comorbidity with disease severity (including hospitalization or pneumonia). RESULTS: Amongst all influenza B positive individuals (n = 446), presence of another upper respiratory pathogen was associated with an increased likelihood of hospitalization (aOR = 2.99 [95% confidence interval (95% CI): 1.14-7.85, p = 0.026]) and pneumonia (aOR = 2.27 [95% CI: 1.25-4.09, p = 0.007]). Chronic lung diseases (CLD) were the strongest predictor for hospitalization (aOR = 3.43 [95% CI: 2.98-3.95, p < 0.001]), but not for pneumonia (aOR = 1.73 [95% CI: 0.80-3.78, p = 0.166]). CONCLUSION: Amongst ED patients infected with influenza B, the presence of other upper respiratory pathogens was independently associated with both hospitalization and pneumonia; presence of CLD was also associated with hospitalization. These findings may be informative for ED clinician's in managing patients infected with influenza B.

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.

Identification of H3N2 NA and PB1-F2 genetic variants and their association with disease symptoms during the 2014-15 influenza season.

The 2014-15 influenza season saw the emergence of an H3N2 antigenic drift variant that formed the 3C.2a HA clade. Whole viral genomes were sequenced from nasopharyngeal swabs of ninety-four patients with confirmed influenza A virus infection and primary human nasal epithelial cell cultures used to efficiently isolate H3N2 viruses. The isolates were classified by HA clade and the presence of a new set of co-selected mutations in NA (a glycosylation site, NAg+) and PB1-F2 (H75P). The NA and PB1-F2 mutations were present in a subset of clade 3C.2a viruses (NAg+F2P), which dominated during the subsequent influenza seasons. In human nasal epithelial cell cultures, a virus with the novel NAg+F2P genotype replicated less well compared with a virus with the parental genotype. Retrospective analyses of clinical data showed that NAg+F2P genotype viruses were associated with increased cough and shortness of breath in infected patients.