bluuebunny/crossref_metadata_2025_split huggingface dataset:
716. Molecular Epidemiology of Respiratory Syncytial Virus in Children and Adults in Seattle, WA
Authors: Scott Emily , Kuypers Jane , Jackson Michael L , Chu Helen 
Published: November 2018

Abstract

Background
Respiratory syncytial virus (RSV) is the most important cause of pneumonia in children &lt;5 years worldwide and may cause severe disease in elderly and high-risk adults. Multiple RSV strains co-circulate and evolve over seasons. We seek to describe the evolution of RSV over five seasons in Seattle, WA, USA with two seasons reported here.

Methods
From 2014 to 2016, subjects 6 months and older seeking outpatient care for acute respiratory illness at Kaiser Permanente Washington were enrolled in the Influenza Vaccine Efficacy Network (Flu VE Network) and a respiratory swab was collected. Real-time polymerase chain reaction (RT-PCR) was performed to test and quantify RSV and subtype positive samples. A subset of RSV samples with cycle threshold (CT) value &lt;30 will be sequenced using a metagenomic next-generation sequencing (NGS) approach. Specific RSV genotypes will be associated with severe disease, defined as requiring emergency department care or hospitalization, or chest radiographic findings.

Results
A total of 8,730 patients were enrolled in the Flu VE Network and PCR testing of seasons 2014/2015 and 2015/2016 resulted in 562 of 4,137 (13.6%) RSV-positive specimens. Of patients with RSV-positive specimens, 204 (36.5%) were adults 18–64 years and 112 (20.0%) were 65+ years. RSV-B predominated in the 2014/2015 season (n = 298; 83.7%), whereas RSV-A was more common in the 2015/2016 season (n = 154; 79.8%) (Figure 1). The median (IQR) CT value for RSV-A specimens was 26.7 (23.3–29.9) compared with 27.9 (25.2–31.3) for RSV-B.

Conclusion
One RSV subtype predominated within each season. Similar RSV subtype distributions were seen across age categories. With multiple RSV vaccine candidates in development, understanding the genetic diversity and circulation of RSV various viruses within a population is important for analyzing the effects of a vaccine on the evolution of RSV.

Figure 1, Total counts (A) and proportions (B) of RSV-A and RSV-B specimens collected from study patients in Seattle, WA during 2014/2015 and 2015/2016 seasons, by age category.

Disclosures
M. L. Jackson, sanofi pasteur: Grant Investigator, Research support. H. Chu, Sanofi-Pasteur: Grant Investigator, Grant recipient.
720. Respiratory and Nonrespiratory Complications Among Patients Hospitalized with Influenza, FluSurv-NET, 2016–2017
Authors: Garg Shikha , Cummings Charisse Nitura , O’Halloran Alissa , Kirley Pam Daily , Herlihy Rachel , Yousey-Hindes Kimberly , Monroe Maya , Eckel Seth , McMahon Melissa , Angeles Kathy , Muse Alison , Bennett Nancy M , Billing Laurie , Thomas Ann , Talbot H Keipp , George Andrea , Anderson Evan J , Reed Carrie 
Published: November 2018

Abstract

Background
Influenza is most commonly associated with respiratory complications; however, nonrespiratory complications occur frequently among patients hospitalized with influenza. We used data from the Influenza Hospitalization Surveillance Network (FluSurv-NET) to describe complications recorded on discharge summaries of patients hospitalized with influenza.

Methods
We included children (0–17 years) and adults (≥18 years), who resided within a FluSurv-NET catchment area and were hospitalized with laboratory-confirmed influenza during 2016–2017. We abstracted data on underlying conditions and discharge diagnoses from medical charts. We calculated the frequency of respiratory and nonrespiratory complications in all age groups and used univariate and multivariable logistic regression to examine factors associated with select complications among adults.

Results
Among 17,489 patients, the most common respiratory complications were pneumonia (26%) and acute respiratory failure (23%) and the most common nonrespiratory complications were sepsis (16%) and acute renal failure (ARF) (12%). Complications varied by age group (figure). Pneumonia was the most common respiratory complication in all age groups except 0–4 years; among children aged 0–4 years bronchiolitis was most common (104/712; 15%). Among 97 children aged 0–4 years with bronchiolitis who underwent testing for respiratory syncytial virus (RSV), 37% had RSV. The most common nonrespiratory complication was seizures in children aged 0–17 years (17% had a history of prior seizures) and sepsis in adults. Among adults (n = 16,057), factors most strongly associated with ARF included chronic renal disease (adjusted odds ratio (AOR) 2.5; 95% confidence interval (95% CI) 2.2–2.8), male sex (AOR 1.5 95% CI 1.4–1.7) and age ≥65 years (AOR 1.4 95% CI 1.2–1.7); the factor most strongly associated with sepsis was chronic neuromuscular disease (AOR 1.5 95% CI 1.3–1.8).

Conclusion
Influenza hospitalizations are associated with a broad spectrum of complications including pneumonia, respiratory failure, sepsis, ARF and seizures. During the influenza season, astute clinicians should keep influenza in the differential diagnosis for patients with a wide range of presentations.

:Disclosures. H. K. Talbot, sanofi pasteur: Investigator, Research grant. Gilead: Investigator, Research grant. MedImmune: Investigator, Research grant. Vaxinnate: Safety Board, none. Seqirus: Safety Board, none. E. J. Anderson, NovaVax: Grant Investigator, Research grant. Pfizer: Grant Investigator, Research grant. AbbVie: Consultant, Consulting fee. MedImmune: Investigator, Research support. PaxVax: Investigator, Research support. Micron: Investigator, Research support.
721. Clinical Respiratory Syndromes and Association with Influenza Clinical Diagnostic Testing and Antiviral Treatment among Children Hospitalized with Acute Respiratory Illness, 2015–2016
Authors: Campbell Angela P , Rha Brian , Ogokeh Constance , Englund Janet , Halasa Natasha B , Selvarangan Rangaraj , Staat Mary A , Weinberg Geoffrey A , Azimi Parvin H , Boom Julie A , McNeal Monica , Sahni Leila C , Singer Monica Nayakwadi , Szilagyi Peter G , Harrison Christopher J , Klein Eileen J , Yu Joana , Figueroa-Downing Daniella , Payne Daniel C , Fry Alicia M 
Published: November 2018

Abstract

Background
We investigated clinical influenza testing and treatment in children hospitalized with acute respiratory illness (ARI) who had distinct respiratory syndromes.

Methods
Children &lt;18 years old with ARI were enrolled at seven hospitals in the New Vaccine Surveillance Network (NVSN) between November 1, 2015–June 30, 2016. ICD10 admission diagnosis codes were grouped to define syndromes of bronchiolitis, asthma, pneumonia, and croup. At clinician discretion, influenza testing with a rapid influenza diagnostic test or molecular assay was performed on respiratory samples. As part of the study, each site performed influenza testing using molecular assays on mid-turbinate nasal and throat swabs from all enrolled children. Analysis was restricted to influenza season; children who received antivirals before hospitalization were excluded.

Results
Among 2,134 children with available ICD10 codes, on preliminary analysis 1,119 (52%) had influenza testing ordered by a clinician: 111 (10%) were positive, and 57 (51%) of 111 received antiviral treatment. Of the 2,134, 858 (40%) had one of the four mutually exclusive syndromes (table). Hospital clinical testing per clinician discretion was influenza positive in 16 of the 858 children (percent positivity per syndrome ranged from &lt;1% to 38%; table). Research study testing of children not undergoing clinical influenza testing identified 11 additional positives. Antiviral treatment was highest for pneumonia patients.

Conclusion
Understanding testing and treatment practices by clinical syndrome may help to identify missed opportunities for influenza diagnosis and treatment.
Table:

Disclosures
J. Englund, Gilead: Consultant and Investigator, Consulting fee and Research support. Novavax: Investigator, Research support. GlaxoSmithKline: Investigator, Research support. Alios: Investigator, Research support. MedImmune: Investigator, Research support. N. B. Halasa, sanofi pasteur: Investigator, Research support. GSK: Consultant, Consulting fee. Moderna: Consultant, Consulting fee.
728. Regional Validation of Distinct RSV Seasonality Thresholds for Antigen and PCR Testing
Authors: Ambrose Christopher S , Steed Lisa L , Brandon Michael , Frye Kara , Thomson Gina 
Published: November 2018

Abstract

Background
Respiratory syncytial virus (RSV) produces annual epidemics that vary in the timing of season onset, peak, and duration by season and by geographic region. Recent analyses by the US Centers for Disease Control at the national level have demonstrated that polymerase chain reaction (PCR) testing has largely replaced rapid antigen testing as the predominant test type and that the traditional 10% positivity threshold for defining an RSV season based on antigen testing should not be applied to PCR testing, for which the comparable threshold for real-time surveillance was 3%. The aim of this study was to validate and model implementation of the antigen (10%) and PCR (3%) positivity thresholds at regional, state, and local levels in a large national dataset of RSV testing results from US hospitals.

Methods
RSV test results were obtained from 599 laboratories that participated from 2011 to 2016 in RSVAlert®, a national RSV surveillance program. For laboratories that provided consistent weekly data (≥10 tests for ≥30 weeks of a season), regional test numbers and positivity were summarized weekly by test type within each season. Season onset and offset were calculated for the 10 US Department of Health and Human Services (HHS) regions and 10 large states plus Hawaii based on (1) antigen only for all seasons, (2) PCR only for all seasons, and (3) the predominant test type used in a specific geography in a season (either antigen or PCR).

Results
An average of 543,340 RSV tests was reported each season. At the regional and state levels, there were fewer outlier estimates of RSV season length when the predominant regional test type was used to define the season (Figures 1 and 2). Exceptions were few and occurred with antigen testing data.

Conclusion
Overall, PCR positivity of 3% was comparable to antigen positivity of 10% at the regional and state levels. Local RSV season determination was most reliable when based on the predominant test type utilized.
Funded by AstraZeneca

Disclosures
C. S. Ambrose, AstraZeneca: Employee, Salary and Stocks.
731. Investigating Clinical Factors Contributing to Continued Antibiotic Therapy in Patients with Viral Upper Respiratory Tract Infections
Authors: Lawandi Alexander , Frenette Charles 
Published: November 2018

Abstract

Background
It has previously been demonstrated that upwards of 50% of patients presenting to Emergency Departments with symptoms of an upper respiratory tract infection receive empirical antibiotics, and that even with a demonstrated viral infection, 70% of these patients are continued on antibiotics. However, the clinical and biochemical factors contributing to this continued therapy is unclear. This study assessed parameters that may impact antibiotic prescriptions in patients with a confirmed viral respiratory infection. Methods. Positive respiratory virus PCRs (RVPs) from nasopharyngeal aspirates performed on adult patients presenting to the McGill University Health Centre Emergency Departments and outpatient clinics over a period of 10 days during the peak of influenza season were included. For each patient, antibiotic administration pre- and post-PCR result were determined, as were the presence of leukocytosis, neutrophilia, an abnormal chest X-ray, and sepsis. Each parameter’s effect on antibiotic use was then determined. Results. During the study period, there were 123 positive RVPs included. These consisted of 34% Flu A, 43% Flu B, and 23% were a mixture of other common respiratory viruses. Antibiotics were administered in 38% of patients before the test was resulted and continued in 79% of these patients afterwards. There was no correlation between the presence of leukocytosis, neutrophilia, signs of sepsis or abnormalities on chest X-ray and continued antibiotic therapy. Conclusion. Despite identification of a respiratory virus infection, patients are routinely treated with antibiotics even without significant evidence of a bacterial process. The impact of testing for respiratory viruses in limiting antibiotic therapy could be improved by education and direct antibiotic stewardship interventions in this population.

Disclosures
All authors: No reported disclosures.
732. Description of Diagnoses and Antibiotic Management of Otitis Media and Otitis Externa in Adults
Authors: Pontefract Benjamin , Madaras-Kelly Karl , Nevers McKenna , Fleming-Dutra Katherine , Samore Matthew 
Published: November 2018

Abstract

Background
Otitis diagnoses include acute otitis media (AOM), otitis media with effusion (OME), and acute otitis externa (AOE). AOM and OME occur primarily in children, whereas AOE occurs with similar frequency in children and adults. Treatment with amoxicillin or close observation without antibiotics is recommended for pediatric AOM, and oral antibiotics are not routinely recommended to treat OME or uncomplicated AOE. Data on otitis diagnoses in adults is limited. This study’s purpose is to characterize the incidence and antibiotic management of otitis diagnoses in adults. Methods. A retrospective cohort of ambulatory veterans who presented at one of six VA Medical Centers during years 2014–2016 with an ICD-9 or -10 code for AOM, OME, and AOE diagnoses was developed. Data extracted included demographics, vital signs, diagnoses, and antibiotic prescriptions. Incident density rates for adult AOM, OME, and AOE were calculated and compared with rates for acute rhinosinusitis. Antibiotic prescribing rates were calculated. Results. Of 4,759 otitis visits identified, the most frequent diagnoses included AOM (38%), OME (25%), and AOE (34%). A single otitis diagnosis was coded in 95.6% of visits and 13.0% had co-diagnosis of another acute respiratory infection (ARI). The incidence density (±95% confidence interval) was 5.4 (5.2, 5.7), 3.6 (3.5, 3.9), and 4.9 (4.7, 5.2) cases per 1,000 patient-years for AOM, OME, and AOE, respectively. For comparison, the incidence density of rhinosinusitis was 16.6 (16.2, 17.0) cases per 1,000 patient-years. Oral antibiotics were prescribed in 48% of visits: AOM (50%), OME (49%), and AOE (47%). Topical antibiotics were prescribed in 32% of AOE visits. The most common oral and otic antibiotics prescribed were amoxicillin/clavulanate (36%), amoxicillin (28%), azithromycin (11%), and hydrocortisone/neomycin/polymyxin (65%), respectively. Conclusion. Otitis diagnoses in adults were common independent of ARI co-diagnoses, but less frequent than rhinosinusitis. Almost half of the patients received an oral antibiotic including those with AOE and OME, indicating a possible focus for antibiotic stewardship programs. Studies to evaluate diagnostic accuracy and treatment of otitis diagnoses in adults are needed.

Disclosures
All authors: No reported disclosures.
734. Post-exposure Management of Influenza in Roommates at a Tertiary Care Cancer Center
Authors: Carlino Sandra , Kamboj Mini 
Published: November 2018

Abstract

Background
Post-exposure antiviral chemoprophylaxis with neuraminidase inhibitors (NI) is 80% effective in preventing influenza in household members. In hospital settings, management of exposed roommates has not been specifically addressed in clinical studies. Some experts recommend immunocompromised individuals exposed to influenza to receive therapeutic doses of NI as a preventive measure regardless of duration of exposure. The objective of this study was to determine optimal intervention in high-risk patients exposed to influenza based on duration of spatial overlap and viral testing at the time exposure is recognized.

Methods
MSK is a 473-bed tertiary care cancer center. Infection Control performs contact investigation for cases diagnosed with influenza including baseline testing of exposed roommates using a multiplex PCR test. The primary team is notified of exposures and makes recommendations regarding prophylaxis. Retrospective review of patients considered exposed to influenza during three seasons was performed. Information on spatial overlap, prophylaxis, and viral testing was extracted.

Results
Out of 64 patients exposed, five (8%) developed influenza (table). Baseline testing was done in 51 (80%): none with overlap of &lt;4 days were symptomatic or tested positive; 2/12 with overlap &gt;4 days tested positive. Attack rate for those with exposure time &lt;4 days who did not receive prophylaxis was 2.6%. No breakthrough infection occurred in the prophylaxis group. Post exposure follow-up revealed two more cases for those overlapping &gt;4 days; a single case of breakthrough infection developed at 7 days, resistance testing was not performed, and patient responded to therapeutic doses of NI without persistent shedding.

Conclusion
Duration of overlap in semi-private rooms correlates with secondary cases of influenza. Prophylactic doses of NI are safe and effective for asymptomatic individuals with exposure &lt;4 days to index case. For patients with spatial overlap &gt;4 days, baseline testing is recommended to recognize cases early and interrupt nosocomial transmission.

Disclosures
All authors: No reported disclosures.
735. Severity and Healthcare Costs of Respiratory Syncytial Virus Hospitalizations in US Preterm Infants Born at 29–34 Weeks Gestation: 2014–2016
Authors: Goldstein Mitchell , Krilov Leonard R , Fergie Jaime , Ambrose Christopher S , Wade Sally , Kong Amanda , Brannman Lance 
Published: November 2018

Abstract

Background
In 2014, the American Academy of Pediatrics recommended against the use of respiratory syncytial virus (RSV) immunoprophylaxis in infants 29–34 weeks gestational age (wGA) at birth without chronic lung disease/bronchopulmonary dysplasia (CLD/BPD) or congenital heart disease (CHD). To inform discussions of the clinical and economic value of RSV immunoprophylaxis in these infants, we compared RSV hospitalization (RSVH) severity and costs incurred by infants hospitalized from 2014–2016 at &lt;6 months chronologic age (CA) for two groups: 29–34 wGA infants without CLD/BPD or CHD and term infants (≥37 wGA) without major health problems.

Methods
Births were identified in the MarketScan Commercial (COM) and Multistate Medicaid (MED) databases. Term and 29–34 wGA infants without CLD/BPD or CHD were selected using DRG and ICD-9/10-CM diagnosis codes. RSVH occurring from Julu 1, 2014 to June 30, 2016 while infants were &lt;6 months CA (the period of highest RSVH incidence) were identified by ICD-9/10-CM diagnosis codes. Severity measures were length of stay (LOS) in days, intensive care unit (ICU) admissions, and healthcare costs (paid amounts on reimbursed hospital claims in 2016 US$). Comparisons between term and 29–34 wGA infants were made with t-tests and chi-squared tests.

Results
There were 1,114 RSVH in the COM data and 3,167 RSVH in the MED data during the study period. Mean LOS was longer for 29–34 wGA infants than term infants for each age category (P &lt; 0.05) and tended to be longer for MED infants vs. COM infants (Figure 1). Thirty-eight percent of COM 29–34 wGA infants and 52% of MED 29–34 wGA infants hospitalized for RSV at &lt;3 months CA were admitted to the ICU (Figure 2). RSVH costs for 29–34 wGA infants were greater than term RSVH costs for each age category (P &lt; 0.05) and were greatest among 29–34 wGA infants hospitalized at &lt;3 months CA: $41,104 for 29–34 wGA COM infants and $24,049 for 29–34 wGA MED infants (Figure 3).

Conclusion
RSVH severity and costs were significantly higher for 29–34 wGA infants without CLD/BPD or CHD relative to term infants. Infants hospitalized at &lt;3 months CA experienced the most severe hospitalizations and incurred the highest costs.
This study was funded by AstraZeneca.

Disclosures
M. Goldstein, AstraZeneca/MedImmune: Consultant, Research grant and Research support. L. R. Krilov, AstraZeneca/MedImmune: Consultant, Research grant and Research support. J. Fergie, AstraZeneca/MedImmune: Consultant and Speaker’s Bureau, Research grant and Research support. C. S. Ambrose, AstraZeneca: Employee, Salary and Stocks. S. Wade, Wade Outcomes Research and Consulting: Employee, Salary. A. Kong, Truven Health Analytics, an IBM Company: Employee, Salary. L. Brannman, AstraZeneca: Employee, Salary and Stocks.
737. The Prevalence of Diagnosed Chronic Lung Disease in US Infants by Gestational Age: Implications for RSV Policy
Authors: Ambrose Christopher S , Jiang Xiaohui , Mavunda Kunjana 
Published: November 2018

Abstract

Background
Perinatal chronic lung disease (CLD), previously referred to as bronchopulmonary dysplasia (BPD), is associated with preterm birth and occurs rarely among term infants. Children with CLD are at elevated risk for severe RSV disease in the first 2 years of life. Definitions of CLD/BPD identify infants who require supplemental oxygen at 28 days of life or 36 weeks postmenstrual age, with no restriction by gestational age (GA) at birth. However, the AAP Committee on Infectious Disease guidance does not recommend RSV immunoprophylaxis for infants with CLD born at ≥32 weeks gestational age (wGA), even though infants with CLD/BPD up to 41 wGA were included in pivotal efficacy studies. This study determined the prevalence of diagnosed CLD in US infants as a function of wGA at birth and the number of infants with CLD born at ≥32 wGA.

Methods
The Kids’ Inpatient Database (KID) is a nationally representative survey conducted every 3 years in the United States. Birth hospitalization data from KID were utilized to estimate the prevalence of CLD (ICD-9 = 770.7) among US infants in 2003–2012 overall and as a function of coincident codes for GA (ICD-9 = 765.21–765.29, reported in 2-week intervals). The prevalence of CLD among 32 wGA infants was imputed based on the distribution of CLD cases as a function of wGA. KID data from 2015 were not available due to the transition to ICD-10 coding.

Results
A total of 31,984 infants had a CLD diagnosis across the 4 years, representing 0.2% of US births. The prevalence of CLD declined from 20.8 to 19.5 per 10,000 between 2003 and 2012. Of those, 25,554 infants with CLD (80%) had GA coded in the database. The percentage of CLD infants born at &lt;27 wGA increased from 44% in 2003 to 52% in 2012, whereas the percentage at ≥29 wGA decreased from 27% to 21% (figure). Overall, the percentages born at 31–32, 33–34, and &gt;34 wGA were 5.7%, 2.2%, and 1.2%, respectively. An estimated 5.7% of infants with CLD were born at ≥32 wGA, representing 0.9 of every 10,000 US births or ~350 infants annually.

Conclusion
Fewer than 400 infants are born at ≥32 wGA and diagnosed with CLD annually in the United States. The rationale for excluding this small but high-risk group of infants from the population recommended for RSV immunoprophylaxis is not clear.
Funded by AstraZeneca

:Disclosures. C. S. Ambrose, AstraZeneca: Employee, Salary and Stocks. X. Jiang, EpiStat Institute: Employee, Consulting fee and Salary. AstraZeneca: Consultant, Consulting fee. K. Mavunda, AstraZeneca: Speaker’s Bureau, Speaker honorarium.