Impact of mechanical ventilation on the daily costs of ICU care: a systematic review and meta regression.

The impact of mechanical ventilation on the daily costs of intensive care unit (ICU) care is largely unknown. We thus conducted a systematic search for studies measuring the daily costs of ICU stays for general populations of adults (age ≥18 years) and the added costs of mechanical ventilation. The relative increase in the daily costs was estimated using random effects meta regression. The results of the analyses were applied to a recent study calculating the excess length-of-stay associated with ICU-acquired (ventilator-associated) pneumonia, a major complication of mechanical ventilation. The search identified five eligible studies including a total of 54 766 patients and ~238 037 patient days in the ICU. Overall, mechanical ventilation was associated with a 25.8% (95% CI 4.7%-51.2%) increase in the daily costs of ICU care. A combination of these estimates with standardised unit costs results in approximate daily costs of a single ventilated ICU day of €1654 and €1580 in France and Germany, respectively. Mechanical ventilation is a major driver of ICU costs and should be taken into account when measuring the financial burden of adverse events in ICU settings.

Multistate methodology improves risk assessment under time-varying drug intake-a new view on pregnancy outcomes following coumarin exposure.

PURPOSE: Observational cohort studies are essential to evaluate the risk of adverse pregnancy outcomes associated with drug intake. Besides left truncation and competing events, it is crucial to account for the time-dynamic pattern of drug exposure. In fact, potentially harmful medications are often discontinued, which might affect the outcome. Ignoring these challenges may lead to biased estimation of drug-related risks highlighting the need for adequate statistical techniques. METHODS: We reanalyze updated data of a recently published study provided by the German Embryotox pharmacovigilance institute. The aim of the study was to quantify the effect of discontinuation of vitamin K antagonist phenprocoumon on the risk of spontaneous abortion. RESULTS: We outline multistate methodology as a powerful method removing bias in probability estimation inherent to commonly used crude proportions. We incorporate time-dependent discontinuation and competing pregnancy outcomes as separate states in a multistate model, which enables the formulation of hazard-based Cox proportional hazard models and the application of so-called landmark techniques. Results show that early discontinuation of phenprocoumon substantially reduces the risk of spontaneous abortion, which is of great importance for both pregnant women and treating physicians. CONCLUSIONS: An adequate handling of discontinuation times is essential when analyzing the risk of spontaneous abortion. The proposed concepts are not restricted to pregnancy outcome studies but have broad usage in other fields of epidemiology. Our nontechnical report may provide guidance for the design and analysis of future studies. Example code is provided.