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Published Data

After identifying potentially eligible publications in our search, we followed a multi- step process for collecting data. We first reviewed the titles and abstracts from the list of citations captured by our search strategy. We eliminated any review articles or articles unrelated to the influenza virus. We continued to screen the articles deemed eligible by our citation review.

In our screening, we utilized a standard set of inclusion criteria (summarized in box 1). These criteria were defined prior to project implementation and based on previous research (Nair et al., 2011; Lafond et al., 2014; Gessner et al., 2011; Simmerman & Uyeki, 2008). The purpose of the criteria was to identify comparable data sources that provided the percent of adult inpatients that tested positive for influenza viruses (our primary outcome), and compare the effects of factors such as year, age group, location, case definition, or influenza diagnostic tool on the positive influenza-tested percentage (secondary outcomes). Article must provide total number tested for influenza and among those tested the total number of influenza positive for adult inpatients. Articles must have data for inpatients. We defined inpatients as patients admitted into the hospital.

Emergency room department admissions were considered outpatients unless later specified that patients required hospitalization. Studies collected data for adults only or reported by age group. Individuals 18 years or older were considered adults if not otherwise noted. To ensure that we included a dataset only once, original research was required. Authors either collected and used data or were the only ones to use data for investigating positive influenza inpatients. Since we are interested in the circulation of influenza among the general population, healthcare-acquired influenza infections were excluded. The circulation of influenza tends to be seasonal in most regions. To control for this seasonality, studies completed at least 12 months of continuous influenza testing.

We required laboratory confirmation of influenza for ensuring accuracy of our primary outcome. Inpatients may present onset and symptoms similar to influenza but do not have an influenza infection according to laboratory test. In light of diagnostic differences in sensitivity and specificity, studies listed the influenza confirmation test. Studies tested a minimum of fifty inpatients for influenza, in attempts to maintain adequate power for estimation and limit type I errors.

Box 1. Inclusion Criteria 1. Adult inpatient data 2. Original research

3. Community-acquired influenza

4. 12 months of continuous influenza testing 5. Laboratory confirmation of influenza 6. Diagnostic test description

7. Total number tested for influenza

8. Total number of influenza positive for adult inpatients 9. Minimum of fifty inpatients for influenza

Once we confirmed that screened article matched the criteria, we abstracted and recorded the outcome measurements and related factors (listed in box 2).

Box 2. Recorded Outcome Measurements 1. Positive percentage of influenza

 What is the total of patients tested for influenza?

 Of this total, how many are positive for influenza, positive for influenza type A and/or influenza type B?

2. Year

 When did the study occur? What are start and end dates?

 Was the study completed during a pandemic or seasonal influenza season? 3. Adult age range

 What is the age range of the adult inpatients tested for influenza?

 If influenza testing results were given by age group, what is the total tested and total positive for the following age groups: 18-45, 45-64, and ≥65?

4. Location

 Where did the studies and testing occur, where were the patients enrolled (city or town, and country)?

 Which WHO region did the study’s or working group collaborator’s country belong to?

 According to the World Bank income standards, would this country be described as high, middle-high, middle-low, or low income?

 Also, would this country during the testing timeframe be described as industrial or undeveloped?

Box 2. Recorded Outcome Measurements 5. Case definition

 What guidelines are used to direct hospital admission and laboratory testing?

 How do authors/work group collaborators define influenza disease in their studies/populations?

6. Influenza diagnostic tool

 What laboratory test was used to confirm suspected cases?

 What type of specimen was collected and tested?

Two or more reviewers completed each step, ensuring that articles were at least doubly reviewed and screened, and that data was doubly abstracted. Any discrepancies between reviewers were discussed. If discussion did resolve discrepancies, reviewers were asked to re-screen and abstract data. Data collection tools were piloted, tested and results evaluated by reviewers, prior to implementation and for training purposes. We found that piloting the collection tools allowed us to ensure that approach by all reviewers was consistent, utilizing the same definitions, and to confirm that our tools captured our outcomes of interest. We also completed a bias assessment, study and outcome level on the eligible articles (box 3).

Box 3. Bias Assessment

Yes = (score) 1. Selection

i. Was a standard criteria, such as a case definition, used in selecting inpatients for influenza testing? (1)

ii. Was the method for selecting inpatients for influenza testing unclear or undefined? (0)

2. Comparability

i. Within the case definition, does the article describe or list symptoms or signs? (1)

ii. Does the article list a syndrome (such as LRTI or community-acquired pneumonia) without describing symptoms (0)?

3. Outcome

a. Reporting

i. Do the authors clearly provide total number of inpatients tested for influenza and of those tested, the number of inpatients who were positive for influenza? (1)

ii. Do authors not clearly provide the total influenza tested and the total positive for influenza? (0)

Unpublished Data

We used a template for collecting standard outcome data from working group participants. Participants provided a basic description of their surveillance system. This basic description includes start year, age group testing, lists of inpatient surveillance sites, case definition used and start time of using definition, sampling strategies used for

influenza testing during influenza and non-influenza seasons, type of sample collected and tested, and the diagnostic method used in influenza testing (method, percentage of samples used with each method used, and when method was used). The template also captured influenza testing by year (start and end date for each testing year, from 2005 to 2012), age group (18-49, 50-64, 65-74, and 75+), and serotype (pH1N1, H3N2, B, and seasonal H1N1). Optionally, participants provided site-level results for influenza-testing by age group. No individual patient data was collected.

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