Our study has some limitations. First, while the relatively large study population and the availability of daily data on time‐varying risk factors represent strengths, our study made use of surveillance data and therefore missed more detailed clinical data, e.g. type of ivAB or the presence of sepsis, that could also be associated with VAP and affect estimated associations for other factors. Second, hospital‐level treatment preferences resulted in low variability within individual hospitals, reducing the power to detect associations on these variables. Third, our results may not be generalizable to other settings. VAP in the Netherlands is usually diagnosed and treated based upon clinical features and/or tracheal aspirate cultures. Therefore, some risk factors may differ when VAP is diagnosed in a more invasive way. Top clinical hospitals were overrepresented in the sample of participating hospitals, whereas academic hospitals did not participate. Along with the variation in VAP rates observed this implies the average VAP incidence density may not be representative of all hospitals. Fourth, we could not distinguish between new and recurrent ICU admissions, which may have led to some overrepresentation of complex patients. Fifth, including only the first ventilation episode may have led to some bias in the assessment of risk factors. Lastly, in‐house infection control professionals collected the data. Apart from the low inter‐observer reliability of diagnosing VAP[31, 32], this may have led to differences in the application of the surveillance protocol. We aimed to minimize this possible bias by arranging meetings for the involved professionals to discuss data collection and infection criteria. Surveillance results are limited for clinical use or pathophysiological insight but the data of Dutch ICUs participating in the VAP surveillance system revealed risk factors on both patient (age, sedation score) and treatment level (SDD, oropharyngeal prophylaxis, other antibiotics, nebulizer type) that can be useful for case mix adjustment and evaluation of VAP prevention strategies. The introduction of SDD or oropharyngeal prophylaxis was associated with low or zero VAP incidences. Surprisingly, COPD was associated with a reduced VAP risk, which merits further evaluation. For some time‐ dependent covariates, the WCE approach was preferable over standard Cox proportional hazard regression and additionally provided insight into the relevant retrospective timeframe of past exposures. ACKNOWLEDGEMENTS We would like to thank the infection control practitioners, intensive care nurses, intensivists and other involved staff in the participating centers for their interest in monitoring VAP in their patients and their willingness to share this information. 4 79 Risk factors for VAP using flexible methods
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