Publications

Erasme University Hospital Brussels, Belgium Address requests for reprints to: Dr. Jean-Louis Vincent, Department of Intensive Care, Erasme University Hospital, Route de Lennik 808, B-1070 Brussels, Belgium.

SCOPUS: le.j

Nitric oxide (NO) is believed to play a key role in the pathogenesis of septic shock, although many aspects of NO's involvement remain poorly defined. Recent years have seen advances in our understanding of the production and effects of NO, but much of the work has been done in animal models and may not be directly relevant to the clinical situation. Differences between species and models can account for many of the apparently conflicting results obtained. Nevertheless, NO-directed strategies have been developed and tested clinically. However, NO can have both beneficial and detrimental effects on many organ systems in sepsis and attempts to nonselectively block all its actions may therefore not yield positive results on outcome. Further exploration and precision of the role of NO and development of techniques to assess the NO balance in individual patients is necessary before further progress can be made in this field.

Platelets play a complex role in sepsis; they are able to modulate not only their own function but also that of cells around them. Further study is needed to better define the precise mechanisms and effects of platelet activation in sepsis and to determine the benefits and risks of inhibiting platelet function.

info:eu-repo/semantics/published

Clinical researchers often select among and evaluate risk prediction models using standard machine learning metrics based on confusion matrices. However, if these models are used to allocate interventions to patients, standard metrics calculated from retrospective data are only related to model utility (in terms of reductions in outcomes) under certain assumptions. When predictions are delivered repeatedly throughout time (e.g. in a patient encounter), the relationship between standard metrics and utility is further complicated. Several kinds of evaluations have been used in the literature, but it has not been clear what the target of estimation is in each evaluation. We synthesize these approaches, determine what is being estimated in each of them, and discuss under what assumptions those estimates are valid. We demonstrate our insights using simulated data as well as real data used in the design of an early warning system. Our theoretical and empirical results show that evaluations without interventional data either do not estimate meaningful quantities, require strong assumptions, or are limited to estimating best-case scenario bounds.