Baseline hospital performance and the impact of medical emergency teams: Modelling vs. conventional subgroup analysis

<p>Abstract</p> <p>Background</p> <p>To compare two approaches to the statistical analysis of the relationship between the baseline incidence of adverse events and the effect of medical emergency teams (METs).</p> <p>Methods</p> <p>Using data from a cluster randomized controlled trial (the MERIT study), we analysed the relationship between the baseline incidence of adverse events and its change from baseline to the MET activation phase using quadratic modelling techniques. We compared the findings with those obtained with conventional subgroup analysis.</p> <p>Results</p> <p>Using linear and quadratic modelling techniques, we found that each unit increase in the baseline incidence of adverse events in MET hospitals was associated with a 0.59 unit subsequent reduction in adverse events (95%CI: 0.33 to 0.86) after MET implementation and activation. This applied to cardiac arrests (0.74; 95%CI: 0.52 to 0.95), unplanned ICU admissions (0.56; 95%CI: 0.26 to 0.85) and unexpected deaths (0.68; 95%CI: 0.45 to 0.90). Control hospitals showed a similar reduction only for cardiac arrests (0.95; 95%CI: 0.56 to 1.32). Comparison using conventional subgroup analysis, on the other hand, detected no significant difference between MET and control hospitals.</p> <p>Conclusions</p> <p>Our study showed that, in the MERIT study, when there was dependence of treatment effect on baseline performance, an approach based on regression modelling helped illustrate the nature and magnitude of such dependence while sub-group analysis did not. The ability to assess the nature and magnitude of such dependence may have policy implications. Regression technique may thus prove useful in analysing data when there is a conditional treatment effect.</p

Strategies for antimicrobial drug delivery to biofilm.

Biofilms are formed by the attachment of single or mixed microbial communities to a variety of biological and/or synthetic surfaces. Biofilm micro-organisms benefit from many advantages of the polymicrobial environment including increased resistance against antimicrobials and protection against the host organism's defence mechanisms. These benefits stem from a number of structural and physiological differences between planktonic and biofilm-resident microbes, but two main factors are the presence of extracellular polymeric substances (EPS) and quorum sensing communication. Once formed, biofilms begin to synthesise EPS, a complex viscous matrix composed of a variety of macromolecules including proteins, lipids and polysaccharides. In terms of drug delivery strategies, it is the EPS that presents the greatest barrier to diffusion for drug delivery systems and free antimicrobial agents alike. In addition to EPS synthesis, biofilm-based micro-organisms can also produce small, diffusible signalling molecules involved in cell density-dependent intercellular communication, or quorum sensing. Not only does quorum sensing allow microbes to detect critical cell density numbers, but it also permits co-ordinated behaviour within the biofilm, such as iron chelation and defensive antibiotic activities. Against this backdrop of microbial defence and cell density-specific communication, a variety of drug delivery systems have been developed to deliver antimicrobial agents and antibiotics to extracellular and/or intracellular targets, or more recently, to interfere with the specific mechanisms of quorum sensing. Successful delivery strategies have employed lipidic and polymeric-based formulations such as liposomes and cyclodextrins respectively, in addition to inorganic carriers e.g. metal nanoparticles. This review will examine a range of drug delivery systems and their application to biofilm delivery, as well as pharmaceutical formulations with innate antimicrobial properties such as silver nanoparticles and microemulsions.University of Wolverhampton, UK ; Universiti Kebangsaan Malaysia, Malaysia