How to handle mortality when investigating length of hospital stay and time to clinical stability

<p>Abstract</p> <p>Background</p> <p>Hospital length of stay (LOS) and time for a patient to reach clinical stability (TCS) have increasingly become important outcomes when investigating ways in which to combat Community Acquired Pneumonia (CAP). Difficulties arise when deciding how to handle in-hospital mortality. Ad-hoc approaches that are commonly used to handle time to event outcomes with mortality can give disparate results and provide conflicting conclusions based on the same data. To ensure compatibility among studies investigating these outcomes, this type of data should be handled in a consistent and appropriate fashion.</p> <p>Methods</p> <p>Using both simulated data and data from the international Community Acquired Pneumonia Organization (CAPO) database, we evaluate two ad-hoc approaches for handling mortality when estimating the probability of hospital discharge and clinical stability: 1) restricting analysis to those patients who lived, and 2) assigning individuals who die the "worst" outcome (right-censoring them at the longest recorded LOS or TCS). Estimated probability distributions based on these approaches are compared with right-censoring the individuals who died at time of death (the complement of the Kaplan-Meier (KM) estimator), and treating death as a competing risk (the cumulative incidence estimator). Tests for differences in probability distributions based on the four methods are also contrasted.</p> <p>Results</p> <p>The two ad-hoc approaches give different estimates of the probability of discharge and clinical stability. Analysis restricted to patients who survived is conceptually problematic, as estimation is conditioned on events that happen <it>at a future time</it>. Estimation based on assigning those patients who died the worst outcome (longest LOS and TCS) coincides with the complement of the KM estimator based on the subdistribution hazard, which has been previously shown to be equivalent to the cumulative incidence estimator. However, in either case the time to in-hospital mortality is ignored, preventing simultaneous assessment of patient mortality in addition to LOS and/or TCS. The power to detect differences in underlying hazards of discharge between patient populations differs for test statistics based on the four approaches, and depends on the underlying hazard ratio of mortality between the patient groups.</p> <p>Conclusions</p> <p>Treating death as a competing risk gives estimators which address the clinical questions of interest, and allows for simultaneous modelling of both in-hospital mortality and TCS / LOS. This article advocates treating mortality as a competing risk when investigating other time related outcomes.</p

DendroPrime as an adhesion barrier on fracture fixation plates : an experimental study in rabbits

We tested the anti-adhesional effect of a new thiol-ene-based coating in a rabbit model. In 12 New Zealand white rabbits, the periosteum and cortex of the proximal phalanx of the second toe of both hind paws was scratched. Stainless steel plates were fixated with screws. One plate was coated with DendroPrime and the other left bare. The non-operated second toes of both hind paws of an additional four rabbits served as controls. Seven weeks after surgery, the soft tissue adhesion to the plates was evaluated macroscopically, and joint mobility was measured biomechanically. Toe joint mobility was about 20% greater and statistically significant in specimens with coated plates compared with the bare plates. Soft tissue overgrowth and, in some cases, synovitis or adhesions between the plate and the tendon were observed on all bare plates but not on any of the coated plates. We conclude that the thiol-ene-based coating can improve joint mobility by about 20%. This material has a potential to reduce adhesion around plates in fracture surgery. © The Author(s) 2020