Evaluating the Liverpool Care Pathway for care of the terminally ill in rural Australia

© 2015, Springer-Verlag Berlin Heidelberg. Purpose: This study evaluates a pilot implementation of the Liverpool Care Pathway (LCP), a clinical tool used to guide the care of dying patients in the last days of life, on the end-of-life care for dying patients in three regions in rural Australia. Methods: The LCP was implemented at 13 participating sites: nine hospitals (general wards), one community-based palliative care service, and three in-hospital palliative care units. To evaluate the implementation of the LCP, 415 eligible patient records were examined: 223 pre-implementation and 192 post-implementation (116 on the LCP and 76 receiving usual care). The primary analysis compared all patients pre-implementation of the LCP versus all patients post-implementation. Results: Increases were found post-implementation for communication with other health professionals and with patients or family (pre-69 %, post-87 %; p ≤ 0.000), use of palliative medications (pre-87 %, post-98 %; p ≤ 0.000) and frequency of symptom assessments (pre-66 %, post-82 %; p ≤ 0.000). Fewer blood and radiological investigations were conducted and venous access devices used in the post-implementation groups than in the pre-implementation period. Conclusions: This study suggests that when rigorously implemented, the LCP improves important components of end-of-life care for dying patients and their families

Glycomimetics; A Novel Class of Drugs to Protect Against Free Fatty Acid-Induced Endothelial Dysfunction

Background Endothelial dysfunction is a key player in cardiovascular disease (CVD) complications and novel drugs are required to treat this pathological process. Glycosaminoglycans (GAGs) are key molecules that regulate signalling in many biological processes and drugs that mimic their structure could be a novel source of therapeutics to target specific CVD pathways. Purpose We have synthesised a set of four glycomimetic compounds and our objective was to determine whether they could activate protective pathways in endothelial cells subjected to fatty acid-induced endothelial dysfunction. Methods Glycomimetics, C1-C4, were synthesised by the stepwise transformation of 2,5-dihydroxybenzoic acid to a range of 2,5-substituted benzoic acid derivatives, incorporating the key sulphate groups to mimic heparan sulphate. Human Umbilical Vein Endothelial Cells (HUVECs) were treated with glycomimetics (1µM) in the presence or absence of the free fatty acid, palmitate. DAF-2 and H2DCF-DA assays were used to determine NO and reactive oxygen species (ROS) production, respectively. Lipid peroxidation colorimetric and antioxidant enzyme activity ssays were also carried out. RT-PCR and western blotting were utilised to measure Akt, eNOS, Nrf-2, NQO-1 and HO-1 expression. Endothelial function was determined ex vivo using acetylcholine-induced endothelium-dependent relaxation in mouse thoracic aortic rings by wire myography. Results All four glycomimetics protected against palmitate-induced oxidative stress and enhanced NO production in vitro via upregulation of Akt/eNOS signalling, activation of the Nrf2/ARE pathway and down-regulation of ROS-induced lipid peroxidation. Under palmitate-induced oxidative stress, ex vivo endothelium-dependent relaxation was significantly enhanced by all four glycomimetics. Furthermore, the glycomimetics did not induce HUVEC activation, as determined by lack of ICAM-1 protein. Conclusion We have developed a new set of small molecule glycomimetics that do not activate ECs and protect against free fatty acid-induced endothelial dysfunction both in vitro and ex vivo. Future work will focus on developing the glycomimetics into drug-like therapies that target endothelial damage

Residential Freire Training

This report highlights activities and training during Freire residential and how volunteers are engaged, empowered and enable

Small Molecule Glycomimetics Inhibit Vascular Calcification via c-Met/Notch3/HES1 Signalling

© Copyright by the Author(s). Published by Cell Physiol Biochem Press. BACKGROUND/AIMS: Vascular calcification represents a huge clinical problem contributing to adverse cardiovascular events, with no effective treatment currently available. Upregulation of hepatocyte growth factor has been linked with vascular calcification, and thus, represent a potential target in the development of a novel therapeutic strategy. Glycomimetics have been shown to interrupt HGF-receptor signalling, therefore this study investigated the effect of novel glycomimetics on osteogenic signalling and vascular calcification in vitro. METHODS: Primary human vascular smooth muscle cells (HVSMCs) were induced by β-glycerophosphate (β-GP) and treated with 4 glycomimetic compounds (C1-C4). The effect of β-GP and C1-C4 on alkaline phosphatase (ALP), osteogenic markers and c-Met/Notch3/HES1 signalling was determined using colorimetric assays, qRT-PCR and western blotting respectively. RESULTS: C1-C4 significantly attenuated β-GP-induced calcification, as shown by Alizarin Red S staining and calcium content by day 14. In addition, C1-C4 reduced ALP activity and prevented upregulation of the osteogenic markers, BMP-2, Runx2, Msx2 and OPN. Furthermore, β-GP increased c-Met phosphorylation at day 21, an effect ameliorated by C2 and C4 and the c-Met inhibitor, crizotinib. We next interrogated the effects of the Notch inhibitor DAPT and confirmed an inhibition of β-GP up-regulated Notch3 protein by C2, DAPT and crizotinib compared to controls. Hes-1 protein upregulation by β-GP, was also significantly downregulated by C2 and DAPT. GOLD docking analysis identified a potential binding interaction of C1-C4 to HGF which will be investigated further. CONCLUSION: These findings demonstrate that glycomimetics have potent anti-calcification properties acting via HGF/c-Met and Notch signalling

Exploring the performance reserve: Effect of different magnitudes of power output deception on 4,000 m cycling time-trial performance

Purpose The aim of the present study was to investigate whether a magnitude of deception of 5% in power output would lead to a greater reduction in the amount of time taken for participants to complete a 4000 m cycling TT than a magnitude of deception of 2% in power output, which we have previously shown can lead to a small change in 4000 m cycling TT performance. Methods Ten trained male cyclists completed four, 4000 m cycling TTs. The first served as a habituation and the second as a baseline for future trials. During trials three and four participants raced against a pacer which was set, in a randomized order, at a mean power output equal to 2% (+2% TT) or 5% (+5% TT) higher than their baseline performance. However participants were misled into believing that the power output of the pacer was an accurate representation of their baseline performance on both occasions. Cardiorespiratory responses were recorded throughout each TT, and used to estimate energy contribution from aerobic and anaerobic metabolism. Results Participants were able to finish the +2% TT in a significantly shorter duration than at baseline (p = 0.01), with the difference in performance likely attributable to a greater anaerobic contribution to total power output (p = 0.06). There was no difference in performance between the +5% TT and +2% TT or baseline trials. Conclusions Results suggest that a performance reserve is conserved, involving anaerobic energy contribution, which can be utilised given a belief that the exercise will be sustainable however there is an upper limit to how much deception can be tolerated. These findings have implications for performance enhancement in athletes and for our understanding of the nature of fatigue during high-intensity exercise

The accuracy of diagnostic coding for acute kidney injury in England - A single centre study

This is the final version. Available on open access from BMC via the DOI in this recordBackground: Acute kidney injury (AKI) is an independent risk factor for mortality and is responsible for a significant burden of healthcare expenditure, so accurate measurement of its incidence is important. Administrative coding data has been used for assessing AKI incidence, and shows an increasing proportion of hospital bed days attributable to AKI. However, the accuracy of coding for AKI and changes in coding over time have not been studied in England. Methods. We studied a random sample of admissions from 2005 and 2010 where ICD-10 code N17 (acute renal failure) was recorded in the administrative coding data at one acute NHS Foundation Trust in England. Using the medical notes and computerised records we examined the demographic and clinical details of these admissions. Results: Against a 6.3% (95% CI 4.8-7.9%) increase in all non-elective admissions, we found a 64% increase in acute renal failure admissions (95% CI 41%-92%, p<0.001) in 2010 compared to 2005. Median age was 78 years (IQR 72-87), 11-25% had a relevant pre-admission co-morbidity and 64% (55-73%) were taking drugs known to be associated with AKI. Over both years, 95% (91-99%) of cases examined met the Kidney Disease: Improving Global Outcomes criteria for AKI. Conclusions: Patients with hospital admissions where AKI has been coded are elderly with multiple co-morbidities. Our results demonstrate a high positive predictive value of coding data for a clinical diagnosis of AKI, with no suggestion of marked changes in coding of AKI between 2005 and 2010. © 2013 Tomlinson et al; licensee BioMed Central Ltd.Cambridge Biomedical Research InstituteBritish Heart Foundatio

Development of a genetic tool for product regulation in the diverse British pig breed market

<p>Abstract</p> <p>Background</p> <p>The application of DNA markers for the identification of biological samples from both human and non-human species is widespread and includes use in food authentication. In the food industry the financial incentive to substituting the true name of a food product with a higher value alternative is driving food fraud. This applies to British pork products where products derived from traditional pig breeds are of premium value. The objective of this study was to develop a genetic assay for regulatory authentication of traditional pig breed-labelled products in the porcine food industry in the United Kingdom.</p> <p>Results</p> <p>The dataset comprised of a comprehensive coverage of breed types present in Britain: 460 individuals from 7 traditional breeds, 5 commercial purebreds, 1 imported European breed and 1 imported Asian breed were genotyped using the PorcineSNP60 beadchip. Following breed-informative SNP selection, assignment power was calculated for increasing SNP panel size. A 96-plex assay created using the most informative SNPs revealed remarkably high genetic differentiation between the British pig breeds, with an average F_ST of 0.54 and Bayesian clustering analysis also indicated that they were distinct homogenous populations. The posterior probability of assignment of any individual of a presumed origin actually originating from that breed given an alternative breed origin was > 99.5% in 174 out of 182 contrasts, at a test value of log(LR) > 0. Validation of the 96-plex assay using independent test samples of known origin was successful; a subsequent survey of market samples revealed a high level of breed label conformity.</p> <p>Conclusion</p> <p>The newly created 96-plex assay using selected markers from the PorcineSNP60 beadchip enables powerful assignment of samples to traditional breed origin and can effectively identify mislabelling, providing a highly effective tool for DNA analysis in food forensics.</p