Hospitalization following outpatient medical care for influenza: US influenza vaccine effectiveness network, 2011‐12—2015‐16

Over five seasons, we determined the proportion of outpatients with laboratory‐confirmed, influenza‐associated illness who were hospitalized within 30 days following the outpatient visit. Overall, 136 (1.7%) of 7813 influenza‐positive patients were hospitalized a median of 4 days after an outpatient visit. Patients aged ≥ 65 years and those with high‐risk conditions were at increased risk of hospitalization. After controlling for age and high‐risk conditions, vaccination status and infecting influenza virus type were not associated with hospitalization risk among adults.

National Institutes of Health (grants UL1 RR024153 and UL1TR000005). All authors assisted in the design and conduct of the study; the collection, management, analysis, and interpretation of the data; preparation, review and approval of the manuscript; and the decision to submit for publication.

| INTRODUC TI ON
Influenza virus infection is associated with a high disease burden.

| ME THODS
We analyzed data collected from the US Influenza Vaccine Effectiveness (Flu VE) Network over five consecutive influenza seasons, from 2011-2012 to 2015-2016. As previously described, the Flu VE Network enrolls patients aged ≥ 6 months seeking medical care within 7 days of illness onset for an acute respiratory illness (ARI) with cough (with cough and/or fever in 2011-2012) at outpatient healthcare facilities (primary care and acute care setting) associated with study sites in Michigan, Pennsylvania, Texas, Washington and Wisconsin. 3 In addition, two study sites (Wisconsin and Pennsylvania) enrolled patients meeting inclusion criteria from emergency departments. Patients who reported receipt of one or more doses of influenza antiviral medication within the past 7 days were excluded from enrollment. Nasal and throat swabs were collected at enrollment for influenza virus testing by reverse transcription polymerase chain reaction (RT-PCR). All patients completed an enrollment interview and provided informed consent for data extraction from medical records. Patients were classified as having a high-risk condition if they had at least one medical encounter during the year before enrollment associated with an International Classification of Diseases (9 th [ICD-9] or 10th [ICD-10] revision) diagnosis code corresponding to a high-risk medical condition as defined by the US Advisory Committee for Immunization Practices (ACIP). 4 Following enrollment, discharge codes for all hospitalizations and Current Procedural Terminology (CPT) codes for imaging procedures ordered (including chest/sinus x-ray and computed tomography scan) within 30 days were identified from electronic medical records (Table S1). A total of 98% of CPT codes were for chest imaging and 2% were for sinus imaging procedures. Hospitalizations associated with diagnostic codes for medically attended acute respiratory infection (MAARI) were also identified (Table S2). Multivariable logistic regression was used to calculate adjusted odds ratios and 95% confidence intervals for predictors of any hospitalization among patients aged ≥ 18 years with laboratory-confirmed influenza within 14 days of enrollment; analysis of risk factors for hospitalizations excluded children aged < 18 years due to low numbers of hospitalizations.
We performed a sub analysis of hospitalization among outpatient adults prescribed antiviral medication ≤ 7 days after enrollment and excluded patients hospitalized on the day of or day after enrollment, before one would expect to see the full effect of antiviral treatment.
Analyses were conducted in SAS version 9.3 (SAS Institute Inc., Cary, NC).

| RE SULTS
Over five influenza seasons, 34 385 patients with ARI were enrolled from primary or acute care settings in the US Flu VE network study and 7813 (22.7%) patients tested RT-PCR positive for influenza. The mean age of enrolled patients with laboratory-confirmed influenza was 32.7 years (range, 9 months to 106 years). The majority were non-Hispanic White (5848; 74.8%), and 4303 (55.1%) were female.

ACK N OWLED G EM ENTS
We would like to thank the U.S. Influenza Vaccine Effectiveness (VE) Network study sites and participants. Corporation. RZ has received research funds from Pfizer Inc. The remaining authors report no conflict of interests.

D I SCL A I M ER
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