The computerized medical record as a tool for clinical governance in australian primary care

Background: Computerized medical records (CMR) are used in most Australian general practices. Although CMRs have the capacity to amalgamate and provide data to the clinician about their standard of care, there is little research on the way in which they may be used to support clinical governance: the process of ensuring quality and accountability that incorporates the obligation that patients are treated according to best evidence. Objective: The objective of this study was to explore the capability, capacity, and acceptability of CMRs to support clinical governance. Methods: We conducted a realist review of the role of seven CMR systems in implementing clinical governance, developing a four-level maturity model for the CMR. We took Australian primary care as the context, CMR to be the mechanism, and looked at outcomes for individual patients, localities, and for the population in terms of known evidence-based surrogates or true outcome measures. Results: The lack of standardization of CMRs makes national and international benchmarking challenging. The use of the CMR was largely at level two of our maturity model, indicating a relatively simple system in which most of the process takes place outside of the CMR, and which has little capacity to support benchmarking, practice comparisons, and population-level activities. Although national standards for coding and projects for record access are proposed, they are not operationalized. Conclusions: The current CMR systems can support clinical governance activities; however, unless the standardization and data quality issues are addressed, it will not be possible for current systems to work at higher levels

The interplay between fluorescence and phosphorescence with luminescent gold(i) and gold(iii) complexes bearing heterocyclic arylacetylide ligands

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Providing alternative measures for addressing adverse drug-drug interactions

First Online 30 March 2019Clinical Practice Guidelines (CPGs) are documents used in daily clinical practice that provide advice on how to best diagnose and treat diseases in the form of a list of clinical recommendations. When simultaneously applying multiple CPGs to patients, this can lead to complex multiple drug regimens (polypharmacy) with the potential for harmful combinations of drugs. The need to address these adverse drug events calls forth for systems capable of not only automatically represent the common potential conflicts or interactions that can happen when merging CPGs but also systems capable of providing conflict-free alternatives. This paper presents a solution that represents CPGs as Computer-Interpretable Guidelines (CIGs) and allows the automatic identification of drug conflicts and the provision of alternative measures to resolve these conflicts.This work has been supported by COMPETE: POCI-01-0145-FEDER-0070 43 and FCT – Fundação para a Ciência e Tecnologia within the Project Scope UID/CEC/ 00319/2013. The work of Tiago Oliveira was supported by JSPS KAKENHI Grant Number JP18K18115

A comparison of liquid and solid culture for determining relapse and durable cure in phase III TB trials for new regimens

BACKGROUND: Tuberculosis kills more people than any other infectious disease, and new regimens are essential. The primary endpoint for confirmatory phase III trials for new regimens is a composite outcome that includes bacteriological treatment failure and relapse. Culture methodology is critical to the primary trial outcome. Patients in clinical trials can have positive cultures after treatment ends that may not necessarily indicate relapse, which was ascribed previously to laboratory cross-contamination or breakdown of old lesions. Löwenstein-Jensen (LJ) medium was the previous standard in clinical trials, but almost all current and future trials will use the Mycobacteria Growth Indicator Tube (MGIT) system due to its simplicity and consistency of use, which will affect phase III trial results. LJ was used for the definition of the primary endpoint in the REMoxTB trial, but every culture was also inoculated in parallel into the MGIT system. The data from this trial, therefore, provide a unique opportunity to investigate and compare the incidence of false 'isolated positives' in liquid and solid media and their potential impact on the primary efficacy results. METHODS: All post-treatment positive cultures were reviewed in the REMoxTB clinical trial. Logistic regression models were used to model the incidence of isolated positive cultures on MGIT and LJ. RESULTS: A total of 12,209 sputum samples were available from 1652 patients; cultures were more often positive on MGIT than LJ. In 1322 patients with a favourable trial outcome, 126 (9.5%) had cultures that were positive in MGIT compared to 34 (2.6%) patients with positive cultures on LJ. Among patients with a favourable outcome, the incidence of isolated positives on MGIT differed by study laboratory (p < 0.0001) with 21.9% of these coming from one laboratory investigating only 4.9% of patients. No other baseline factors predicted isolated positives on MGIT after adjusting for laboratory. There was evidence of clustering of isolated positive cultures in some patients even after adjusting for laboratory, p < 0.0001. The incidence of isolated positives on MGIT did not differ by treatment arm (p = 0.845, unadjusted). Compared to negative MGIT cultures, positive MGIT cultures were more likely to be associated with higher grade TB symptoms reported within 7 days either side of sputum collection in patients with an unfavourable primary outcome (p < 0.0001) but not in patients with a favourable outcome (p = 0.481). CONCLUSIONS: Laboratory cross-contamination was a likely cause of isolated positive MGIT cultures which were clustered in some laboratories. Certain patients had repeated positive MGIT cultures that did not meet the definition of a relapse. This pattern was too common to be explained by cross-contamination only, suggesting that host factors were also responsible. We conclude that MGIT can replace LJ in phase III TB trials, but there are implications for the definition of the primary outcome and patient management in trials in such settings. Most importantly, the methodologies differ in the incidence of isolated positives and in their capacity for capturing non-tuberculosis mycobacteria. It emphasises the importance of effective medical monitoring after treatment ends and consideration of clinical signs and symptoms for determining treatment failure and relapse

Bioinformatics advances in saliva diagnostics

There is a need recognized by the National Institute of Dental & Craniofacial Research and the National Cancer Institute to advance basic, translational and clinical saliva research. The goal of the Salivaomics Knowledge Base (SKB) is to create a data management system and web resource constructed to support human salivaomics research. To maximize the utility of the SKB for retrieval, integration and analysis of data, we have developed the Saliva Ontology and SDxMart. This article reviews the informatics advances in saliva diagnostics made possible by the Saliva Ontology and SDxMart

Tethered N-Heterocyclic Carbene-Carboranyl Silver Complexes for Cancer Therapy

Silver complexes of tethered N-heterocyclic carbene-carboranyl ligands have been prepared and fully characterized. The first example of silver bonded directly to the cage of o-carborane has been identified in the solid state. The presence of a carboranyl N substituent on the N-heterocyclic carbene significantly enhances the in vitro cytotoxicity of the silver complex against HCT116 p53+/+ and HCT116 p53–/– colon cancer cells in comparison to a phenyl derivative. Conversely, the presence of a carboranyl on the backbone of a xanthine-derived N-heterocyclic carbene decreases the in vitro cytotoxicity of the silver complex in comparison to its phenyl derivative. Stability studies on the xanthine-derived ligands and complexes show that decomposition via deboronation occurs in hydrous dimethyl sulfoxide, which may attribute to the contrasting in vitro behaviors of the carborane-containing complexes

Crystal structure of a quinoenzyme: copper amine oxidase of Escherichia coli at 2 å resolution

AbstractBackground: Copper amine oxidases are a ubiquitous and novel group of quinoenzymes that catalyze the oxidative deamination of primary amines to the corresponding aldehydes, with concomitant reduction of molecular oxygen to hydrogen peroxide. The enzymes are dimers of identical 70–90 kDa subunits, each of which contains a single copper ion and a covalently bound cofactor formed by the post-translational modification of a tyrosine side chain to 2,4,5-trihydroxyphenylalanine quinone (TPQ).Results The crystal structure of amine oxidase from Escherichia coli has been determined in both an active and an inactive form. The only structural differences are in the active site, where differences in copper coordination geometry and in the position and interactions of the redox cofactor, TPQ, are observed. Each subunit of the mushroom-shaped dimer comprises four domains: a 440 amino acid C-terminal β sandwich domain, which contains the active site and provides the dimer interface, and three smaller peripheral α/β domains (D1–D3), each of about 100 amino acids. D2 and D3 show remarkable structural and sequence similarity to each other and are conserved throughout the quinoenzyme family. In contrast, D1 is absent from some amine oxidases. The active sites are well buried from solvent and lie some 35 å apart, connected by a pair of β hairpin arms.Conclusion The crystal structure of E. coli copper amine oxidase reveals a number of unexpected features and provides a basis for investigating the intriguing similarities and differences in catalytic mechanism of members of this enzyme family. In addition to the three conserved histidines that bind the copper, our studies identify a number of other conserved residues close to the active site, including a candidate for the catalytic base and a fourth conserved histidine which is involved in an interesting intersubunit interaction

Plucking enhanced beneath ice sheet margins: evidence from the Grampian Mountains, Scotland

Concentrations of boulders are a common feature of landscapes modified by former mid-latitude ice sheets. In many cases, the origin of the boulders can be traced in the up-ice direction to a cliff only tens to hundreds of metres distant. The implication is that a pulse of plucking and short boulder transport occurred beneath thin ice at the end of the last glacial cycle. Here we use a case study in granite bedrock in the Dee Valley, Scotland, to constrain theory and explore the factors involved in such a late phase of plucking. Plucking is influenced by ice velocity, hydrology, effective ice pressure, the extent of subglacial cavities and bedrock characteristics. The balance between these factors favours block removal beneath thin ice near a glacier margin. At Ripe Hill in the Dee Valley, a mean exposure age of 14.2 ka on blocks supports the view that the boulder train formed at the end of ice sheet glaciation. The late pulse of plucking was further enhanced by ice flowing obliquely across vertical joints and by fluctuations in sub-marginal meltwater conditions. An implication of the study is that there is the potential for a wave of ice-marginal plucking to sweep across a landscape as an ice sheet retreats