RESUMO
Use of automated dispensing cabinets (ADCs) is increasing in hospital settings. ADCs bring various potential benefits, among which are improvements to patient safety and reduction of medication errors. A core function of ADCs is to prevent medication stock outs by triggering an order when stock is reaching low levels. A quantifiable patient safety measure is the occurrence of omitted or delayed doses, which can range in severity from being negligible, to potentially fatal. The purpose of this review is to identify and synthesise the existing evidence regarding the impact of ADCs situated in secondary and tertiary care inpatient settings, on the rate of omitted and delayed doses as a specific subsection of medication errors. In April 2024 searches were conducted in Embase, PubMed and CINAHL, with additional articles discovered through citation searching and from colleagues. A total of 375 articles were returned from the search. Nine articles met the inclusion criteria. The most common reason for exclusion was due to lack of relevance. The included papers were focused on centres which had implemented six or fewer ADCs. The studies mostly presented findings which suggest ADCs have a positive impact on the rate of omitted or delayed doses, although crucially only two papers correlated missed doses due to unavailability of medications The studies highlighted other factors which should be considered prior to the implementation of ADCs. Factors included staffing requirement, type of stock held in the cabinets, and interoperability with other systems. Studies only reported omitted or missed doses, none reported results on delayed doses. It is widely accepted that ADCs can prevent medication unavailability but there is a paucity of evidence linking the improved availability of medications through the utilisation of ADCs with the perceived impact on missed or delayed doses. Further multi-centre studies are needed to determine this causality.
RESUMO
Matrix remodeling is a consequence of tightly regulated matrix metalloproteinase (MMP) activity. MMPs are synthesized as inactive precursors with auto-inhibitory N-terminal propeptides, the proteolytic removal of which exposes the catalytic zinc ion, rendering the protease active. The regulation of MMP activation has been investigated primarily in tissue culture and biochemical assays that lack important biological context. Here we present the epitope-mediated MMP activation (EMMA) assay and use it to observe the activation of Mmp2 (gelatinase A) by endogenous mechanisms in the intact zebrafish embryo. The hemagglutinin (HA) and GFP-tagged reporter construct becomes activated on the surface of specific cells and this activation is abolished by broad-spectrum inhibition of metalloproteinase activity, consistent with existing models of gelatinase A activation. The mechanism(s) acting on the construct are spatially restricted, metalloproteinase-dependent and replacing the HA tag with mCherry abolishes activation, showing that the mechanism(s) are sensitive to the structure of the N-terminal domain. The construct is activated strongly in maturing myotome boundaries, but also intracellularly within myofibrils, consistent with reports implicating this protease in muscle development and function. In addition to general-purpose tools for the production of "EMMAed" MMPs and other proteins, we have established a transgenic line of zebrafish expressing EMMAedMmp2 under control of an inducible promoter to facilitate further investigation into the regulation of this ubiquitous ECM-remodeling protease in vivo.
