INTRODUCTION Invasively ventilated patients are at an increased risk of acquiring pneumonia, leading to longer hospital stays and increased mortality. Ventilator‐associated pneumonia (VAP) rates ranging from 2 to over 20/1000 ventilation days have been reported[1‐3] with attributable mortality of 1‐13%, depending on the method used and patient specialty[4‐ 7]. Cassini et al estimated that healthcare‐associated pneumonia, including VAP, leads to a burden of 169 (95%CI 149‐192) disability‐adjusted life years per 100,000 total population, more than any other healthcare‐associated infection[8]. Several patient and treatment characteristics have been demonstrated to be associated with the risk to develop VAP, such as Glasgow coma scale, Apache II score, intubation site, length of hospital/ICU stay before ventilation, neutropenia, stress ulcer prophylaxis, corticosteroids, systemic antibiotics and enteral feeding[9‐18]. Some of these patient and treatment characteristics are time‐dependent. Longer exposure or treatment will modify the (cumulative) risk, but it is less clear and often not evaluated how the association of these time‐dependent risks develop during and following exposure[9, 10, 12, 16, 17, 19‐21]. In this manuscript we present the VAP surveillance results and evaluate the risk factors. For the time‐dependent risk factors we use both standard Cox regression and the flexible Weighted Cumulative Effects (WCE) approach that evaluates both current and past exposures[22]. The WCE approach allows estimation of the timeframe during which a risk factor is (still) relevant. MATERIAL AND METHODS Study setting and set up PREZIES (Prevention of HAI through Surveillance) is the Dutch national surveillance network for healthcare associated infections, hosted by the National Institute for Public Health and the Environment (RIVM), in which hospitals participate voluntarily. Since 1996, PREZIES offers Dutch hospitals the possibility to participate in the surveillance of hospital‐acquired infections with attendant benchmarks. The VAP surveillance module was offered from January 2004 ̶ December 2011. The VAP surveillance protocol was developed by a working group of relevant professionals (intensivist, infectious disease specialist, pulmonologist, anaesthesiologist, epidemiologist and infection control professional) and was based on international literature, the preceding ICU‐surveillance conducted by PREZIES [23] and a pilot study. The VAP definition used (Fig 1) was a simplified version of that used by the former Centers for Disease Control and Prevention/National Nosocomial Infections Surveillance system, currently the National Healthcare Safety Network definitions. In Dutch clinical 4 61 Risk factors for VAP using flexible methods
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