BackgroundTo develop content validity of a comprehensive patient-reported outcome (PRO) measure following current best scientific methodology to standardize assessment of influenza (flu) symptoms in clinical research.MethodsStage I (Concept Elicitation): 1:1 telephone interviews with influenza-positive adults (≥18 years) in the US and Mexico within 7 days of diagnosis. Participants described symptom type, character, severity, and duration. Content analysis identified themes and developed the draft Flu-PRO instrument. Stage II (Cognitive Interviewing): The Flu-PRO was administered to a unique set of influenza-positive adults within 14 days of diagnosis; telephone interviews addressed completeness, respondent interpretation of items and ease of use.ResultsSamples: Stage I: N = 46 adults (16 US, 30 Mexico); mean (SD) age: 38 (19), 39 (14) years; % female: 56 %, 73 %; race: 69 % White, 97 % Mestizo. Stage II: N = 34 adults (12 US, 22 Mexico); age: 37 (14), 39 (11) years; % female: 50 %, 50 %; race: 58 % White, 100 % Mestizo. Symptoms: Symptoms identified by >50 %: coughing, weak or tired, throat symptoms, congestion, headache, weakness, sweating, chills, general discomfort, runny nose, chest (trouble breathing), difficulty sleeping, and body aches or pains. No new content was uncovered during Stage II; participants easily understood the instrument.ConclusionsResults show the 37-item Flu-PRO is a content valid measure of influenza symptoms in adults with a confirmed diagnosis of influenza. Research is underway to evaluate the suitability of the instrument for children and adolescents. This work can form the basis for future quantitative tests of reliability, validity, and responsiveness to evaluate the measurement properties of Flu-PRO for use in clinical trials and epidemiology studies.

Background Little is known about HBoV persistence and shedding and the association between HBoV detection and the onset and resolution of respiratory symptoms. Methods We performed HBoV testing on nasal swabs from a prospective, longitudinal study of respiratory illness in 119 children attending daycare. Results HBoV was detected in 70 children (59%), and in 106 (33%) of the 318 study illnesses. Another virus was detected in 76 HBoV+ illnesses (72%). Extended and intermittent shedding was observed, with consistent HBoV detection documented for up to 75 days. HBoV was detected in 20 of 45 asymptomatic enrollment samples (44%) and HBoV prevalence and viral load did not differ significantly between children with and without symptoms at enrollment. HBoV+ illnesses were longer than HBoV- illnesses (OR: 2.44 for symptoms > 7 days, 95% C.I. 1.41, 4.22) and illnesses with HBoV viral load ≥ 4 log-copies/mL required a visit to a health care provider more often than HBoV-illnesses (OR: 1.64, 95% C.I.: 1.02, 2.64). Conclusion HBoV was more common in illnesses with greater severity. However, detection of HBoV was not associated with the presence of respiratory illness or with specific respiratory symptoms in this prospective study of infants and toddlers attending center-based daycare.