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.

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.

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.

Performance of the inFLUenza Patient-Reported Outcome (FLU-PRO) diary in patients with influenza-like illness (ILI).

BACKGROUND: The inFLUenza Patient Reported Outcome (FLU-PRO) measure is a daily diary assessing signs/symptoms of influenza across six body systems: Nose, Throat, Eyes, Chest/Respiratory, Gastrointestinal, Body/Systemic, developed and tested in adults with influenza. OBJECTIVES: This study tested the reliability, validity, and responsiveness of FLU-PRO scores in adults with influenza-like illness (ILI). METHODS: Data from the prospective, observational study used to develop and test the FLU-PRO in influenza virus positive patients were analyzed. Adults (≥18 years) presenting with influenza symptoms in outpatient settings in the US, UK, Mexico, and South America were enrolled, tested for influenza virus, and asked to complete the 37-item draft FLU-PRO daily for up to 14-days. Analyses were performed on data from patients testing negative. Reliability of the final, 32-item FLU-PRO was estimated using Cronbach's alpha (α; Day 1) and intraclass correlation coefficients (ICC; 2-day reproducibility). Convergent and known-groups validity were assessed using patient global assessments of influenza severity (PGA). Patient report of return to usual health was used to assess responsiveness (Day 1-7). RESULTS: The analytical sample included 220 ILI patients (mean age = 39.3, 64.1% female, 88.6% white). Sixty-one (28%) were hospitalized at some point in their illness. Internal consistency reliability (α) of FLU-PRO Total score was 0.90 and ranged from 0.72-0.86 for domain scores. Reproducibility (Day 1-2) was 0.64 for Total, ranging from 0.46-0.78 for domain scores. Day 1 FLU-PRO scores correlated (≥0.30) with the PGA (except Gastrointestinal) and were significantly different across PGA severity groups (Total: F = 81.7, p<0.001; subscales: F = 6.9-62.2; p<0.01). Mean score improvements Day 1-7 were significantly greater in patients reporting return to usual health compared with those who did not (p<0.05, Total and subscales, except Gastrointestinal and Eyes). CONCLUSIONS: Results suggest FLU-PRO scores are reliable, valid, and responsive in adults with influenza-like illness.

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.

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.

The frequency of influenza and bacterial coinfection: a systematic review and meta-analysis.

AIM: Coinfecting bacterial pathogens are a major cause of morbidity and mortality in influenza. However, there remains a paucity of literature on the magnitude of coinfection in influenza patients. METHOD: A systematic search of MeSH, Cochrane Library, Web of Science, SCOPUS, EMBASE, and PubMed was performed. Studies of humans in which all individuals had laboratory confirmed influenza, and all individuals were tested for an array of common bacterial species, met inclusion criteria. RESULTS: Twenty-seven studies including 3215 participants met all inclusion criteria. Common etiologies were defined from a subset of eight articles. There was high heterogeneity in the results (I(2)  = 95%), with reported coinfection rates ranging from 2% to 65%. Although only a subset of papers were responsible for observed heterogeneity, subanalyses and meta-regression analysis found no study characteristic that was significantly associated with coinfection. The most common coinfecting species were Streptococcus pneumoniae and Staphylococcus aureus, which accounted for 35% (95% CI, 14%-56%) and 28% (95% CI, 16%-40%) of infections, respectively; a wide range of other pathogens caused the remaining infections. An assessment of bias suggested that lack of small-study publications may have biased the results. CONCLUSIONS: The frequency of coinfection in the published studies included in this review suggests that although providers should consider possible bacterial coinfection in all patients hospitalized with influenza, they should not assume all patients are coinfected and be sure to properly treat underlying viral processes. Further, high heterogeneity suggests additional large-scale studies are needed to better understand the etiology of influenza bacterial coinfection.

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.

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.

Improving Emergency Providers' Attitudes Toward Sickle Cell Patients in Pain.

BACKGROUND: Provider biases and negative attitudes are recognized barriers to optimal pain management in sickle cell disease, particularly in the emergency department (ED). MEASURES: This prospective cohort measures preintervention and postintervention providers' attitudes toward patients with sickle pain crises using a validated survey instrument. INTERVENTION: ED providers viewed an eight-minute online video that illustrated challenges in sickle cell pain management, perspectives of patients and providers, as well as misconceptions and stereotypes of which to be wary. OUTCOMES: Ninety-six ED providers were enrolled. Negative attitude scoring decreased, with a mean difference -11.5 from baseline, and positive attitudes improved, with a mean difference +10. Endorsement of red-flag behaviors similarly decreased (mean difference -12.8). Results were statistically significant and sustained on repeat testing three months after intervention. CONCLUSIONS/LESSONS LEARNED: Brief video-based educational interventions can improve emergency providers' attitudes toward patients with sickle pain crises, potentially curtailing pain crises early, improving health outcomes and patient satisfaction scores.

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.