57 Narcolepsy Type 1 2013 Incidence Peak adolescents. In addition we confirmed the peak in 2009–2010 pandemic H1N1 influenza that has already been identified in China and in some individual European countries. We consider our results as robust since we used a more sensitive model to analyse the data and, for the first time, took the delayed diagnosis into account, which was a major bias of previous studies. Several other aspects of our findings, in particular the age-specificity, the subacute disease onset of these de novo children/adolescents’ cases and the restrained use of Pandemrix after 2010 allow us to argue for a new epidemiological event triggering the increased NT1 cases in 2013. Methodological aspects: are our results robust? We first applied the same ARIMA prediction models that have already demonstrated an increased NT1 incidence in 2009–2010 H1N1 influenza season in China [60], to confirm an increased number of NT1 patients in 2010 Europe wide. Unfortunately, the ARIMA models are less informative, because they cannot include data after 2009–2011 to exploit their contributions to the prediction of the 2009–2011 incidences. Due to inherent methodological reasons ARIMA models are powerful to forecast future data points based on previous data (“forward prediction”), whereas ARIMA is unable to use data following the forecasted data points (“backward prediction”) [147]. The exclusion of data after 2009–2011 however is specifically problematic for diseases with delayed diagnosis like narcolepsy and is one of the major biases of previous studies [57, 140]. Narcolepsy diagnosis delays of months or even years make it difficult to identify the exposures that contribute to disease development. We therefore ran an additional, more sensitive overall prediction model (LOESS), since it incorporates all available data both before and after the 2009–2010 pH1N1. The longer follow-up (2012–2016) in our database also allows us to identify more patients with a disease onset in 2009–2011. Accordingly, a considerable proportion (35.7%) of the patients starting EDS in 2009–2011, finally diagnosed after 2012, are included in our analysis. The superiority of the LOESS over ARIMA models is evident in the narrower predictive CIs. In summary, by using a more sensitive model with all available data, our analyses provide a better picture of the yearly incidences of NT1 in Europe. Increases of NT1 cases in 2010 and 2013 This study, for the first time, finds a significantly increased number of new NT1 patients in 2013. It also confirms the peak in 2010 that has been previously reported in Finland [56, 135] and France [134, 135]. The 2013 increase is age-specific and specifically robust in France, the Netherlands, Italy, and 2
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