Determination of emergency nurse practitioner and plastic surgery trainee disposition decision agreement for plastic surgery emergency department presentations: A prospective study.

OBJECTIVE: To examine if there was a high degree of agreement for disposition decisions of emergency nurse practitioners (ENP) compared to plastic surgery trainees (PST) for plastic surgery presentations. METHODS: A prospective study of disposition decision agreement from February 2020 to January 2021 for patients who required plastic surgery consultation and managed exclusively by an ENP. Absolute percentages were used to determine the exact disposition decision accuracy of ENP and the PST, while Cohen's kappa compared disposition decision agreement. Sub-analyses of age, gender, ENP experience and presenting condition agreement were also completed. To mitigate confounding factors, operative management (OM) and non-OM groups were analysed. RESULTS: The study recruited 342 patients who presented mostly with finger or hand-related conditions (82%, n = 279) and managed by an ENP with less than 10 years of experience (65%, n = 224). Disposition decisions by ENP compared to PST were the same in 80% (n = 274) of cases. Disposition agreement for all patients was 0.72 (95% confidence interval 0.66-0.78). For the OM and non-OM groups, disposition decisions were the same in 94% (n = 320), with a Cohen's kappa 0.85 (95% confidence interval 0.79-0.91). Seven patients (2%) were discharged to GP care by the ENP when determined to need further plastic surgery involvement by the PST. CONCLUSIONS: Disposition decisions by ENP and PST were the same in most cases and had a high overall level of agreement. This may lead to greater autonomy of ENP care and reduced ED length of stay and occupancy.

NQO1: A target for the treatment of cancer and neurological diseases, and a model to understand loss of function disease mechanisms.

NAD(P)H quinone oxidoreductase 1 (NQO1) is a multi-functional protein that catalyses the reduction of quinones (and other molecules), thus playing roles in xenobiotic detoxification and redox balance, and also has roles in stabilising apoptosis regulators such as p53. The structure and enzymology of NQO1 is well-characterised, showing a substituted enzyme mechanism in which NAD(P)H binds first and reduces an FAD cofactor in the active site, assisted by a charge relay system involving Tyr-155 and His-161. Protein dynamics play important role in physio-pathological aspects of this protein. NQO1 is a good target to treat cancer due to its overexpression in cancer cells. A polymorphic form of NQO1 (p.P187S) is associated with increased cancer risk and certain neurological disorders (such as multiple sclerosis and Alzheimer´s disease), possibly due to its roles in the antioxidant defence. p.P187S has greatly reduced FAD affinity and stability, due to destabilization of the flavin binding site and the C-terminal domain, which leading to reduced activity and enhanced degradation. Suppressor mutations partially restore the activity of p.P187S by local stabilization of these regions, and showing long-range allosteric communication within the protein. Consequently, the correction of NQO1 misfolding by pharmacological chaperones is a viable strategy, which may be useful to treat cancer and some neurological conditions, targeting structural spots linked to specific disease-mechanisms. Thus, NQO1 emerges as a good model to investigate loss of function mechanisms in genetic diseases as well as to improve strategies to discriminate between neutral and pathogenic variants in genome-wide sequencing studies.