Despite the underlying differences in LAIV-vaccinated, TIV-vaccinated, and unvaccinated populations, the

inclusion of TIV-vaccinated and unvaccinated control groups in the study design was valuable to enhance the ability to interpret the study data. If there had been a large, true increased risk of a specific event among LAIV recipients, it would have been detectable in comparison with TIV-vaccinated controls despite the underlying differences in the study populations. Similarly, the lack of an increase relative to unvaccinated controls despite the underlying bias provides evidence that an event is Selleckchem KRX 0401 likely not increased in LAIV recipients. However, given the underlying biases for the comparisons to TIV-vaccinated and unvaccinated controls, the single most valuable comparison appears to be the BLU9931 datasheet self-control analysis as it controls for many of the covariates that are uncontrolled in analyses comparing disparate groups. It is reassuring that very few events were detected

at an increased rate after LAIV vaccination in the self-control analysis, that those detected were generally due to minor illness, and that no statistically significant differences in the self-control analyses remained after adjusting for multiple comparisons. Because previous studies demonstrated that LAIV was associated with an increase in medically attended wheezing events in young children [3] and [4], a comprehensive analysis of wheezing and asthma events was conducted. Events of asthma and wheezing were found to be decreased after vaccination others with LAIV in all settings combined, the clinic setting, and the ED setting; within 21, 42, and 180 days of vaccination; in both age groups; after dose 1 and dose 2; and in comparison to all 3 control groups. There were no increased rates of events of asthma and wheezing after LAIV in any rate comparisons. As described above, differences in the health status of the 2 populations likely explain

the reduced rates of events within the LAIV-vaccinated versus TIV-vaccinated populations. However, it is reassuring that the rate of wheezing and asthma was not increased in any comparisons, particularly those compared with unvaccinated subjects and the self-control analysis. Strengths of the current study include the large sample size, the ability to examine all MAEs for any diagnosis, and the ability to capture events after the real-world use of LAIV over multiple influenza seasons. However, as discussed above, the nonrandomized design of the study is likely responsible for many of the observed differences between comparison groups. Furthermore, this study design did not allow for the systematic determination of whether an event observed after vaccination was the result of a pre-existing condition; evaluations of prior medical history were only feasible for select subjects through detailed chart review.