Electronic prescribing - how does it affect the ward pharmacist?

It is likely that electronic prescribing will be a common feature in tomorrow’s hospitals. However, we do not yet know how its introduction will affect the practice of hospital pharmacists. We are evaluating a closed-loop electronic prescribing, automated dispensing, bar-coded administration system (ServeRx) on one surgical ward. As part of this evaluation, we wanted to explore its impact on the ward pharmacist. Our objectives were to assess the impact of ServeRx on the time spent providing a ward pharmacy service, and on the activities undertaken

Exploring the anthelmintic properties of Australian native shrubs with respect to their potential role in livestock grazing systems

We measured in vitro anthelmintic activity in extracts from 85 species of Australian native shrub, with a view to identifying species able to provide a degree of worm control in grazing systems. Approximately 40% of the species showed significant activity in inhibiting development of Haemonchus contortus larvae. The most active extracts showed IC50 values of 60–300 mg/ml. Pre-incubation with polyvinylpolypyrrolidine removed the activity from some extracts, implicating tannins as the bioactive agent, while in other cases the pre-incubation had no effect, indicating the presence of other anthelmintic compounds. Plant reproductive maturity (onset of flowering or fruiting) was associated with increasing anthelmintic activity in some species. Variability was observed between plants of the same species growing in different environments, while variation between individual plants of the same species within a single field suggests the existence of distinct chemotypes. Significant activity against adult H. contortus worms in vitro was also demonstrated in a limited number of extracts tested against this life stage. Our study indicates that there is potential for Australian native shrubs to play an anthelmintic role in grazing systems, and highlights some plant biology factors which will need to be considered in order to maximize any anthelmintic effects.A. C. Kotze, J. O’Grady, J. Emms, A. F. Toovey, S. Hughes, P. Jessop, M. Bennell P. E. Vercoe and D. K. Revel

Reciprocal regulation by the CepIR and CciIR quorum sensing systems in Burkholderia cenocepacia

<p>Abstract</p> <p>Background</p> <p><it>Burkholderia cenocepacia </it>belongs to a group of closely related organisms called the <it>B. cepacia </it>complex (Bcc) which are important opportunistic human pathogens. <it>B. cenocepacia </it>utilizes a mechanism of cell-cell communication called quorum sensing to control gene expression including genes involved in virulence. The <it>B. cenocepacia </it>quorum sensing network includes the CepIR and CciIR regulatory systems.</p> <p>Results</p> <p>Global gene expression profiles during growth in stationary phase were generated using microarrays of <it>B. cenocepacia cepR</it>, <it>cciR </it>and <it>cepRcciIR </it>mutants. This is the first time CciR was shown to be a global regulator of quorum sensing gene expression. CepR was primarily responsible for positive regulation of gene expression while CciR generally exerted negative gene regulation. Many of the genes that were regulated by both quorum sensing systems were reciprocally regulated by CepR and CciR. Microarray analysis of the <it>cepRcciIR </it>mutant suggested that CepR is positioned upstream of CciR in the quorum sensing hierarchy in <it>B. cenocepacia</it>. A comparison of CepIR-regulated genes identified in previous studies and in the current study showed a substantial amount of overlap validating the microarray approach. Several novel quorum sensing-controlled genes were confirmed using qRT-PCR or promoter::<it>lux </it>fusions. CepR and CciR inversely regulated flagellar-associated genes, the nematocidal protein AidA and a large gene cluster on Chromosome 3. CepR and CciR also regulated genes required for iron transport, synthesis of extracellular enzymes and surface appendages, resistance to oxidative stress, and phage-related genes.</p> <p>Conclusion</p> <p>For the first time, the influence of CciIR on global gene regulation in <it>B. cenocepacia </it>has been elucidated. Novel genes under the control of the CepIR and CciIR quorum sensing systems in <it>B. cenocepacia </it>have been identified. The two quorum sensing systems exert reciprocal regulation of many genes likely enabling fine-tuned control of quorum sensing gene expression in <it>B. cenocepacia </it>strains carrying the cenocepacia island.</p

Fatty acid composition, shelf-life and eating quality of beef from steers fed corn or wheat dried distillers' grains with solubles in a concentrate supplement to grass silage

Thirty-six steers were randomly assigned to one of three dietary treatments fed ad libitum grass silage and concentrate supplements containing either barley/soybean meal (CON), 80% DM corn (CDGS)- or 80% DM wheat (WDGS)-dried distillers' grains with solubles for 124 days pre-slaughter. Chemical and fatty acid composition, shelf-life, and eating quality of longissimus thoracis muscle were determined. Dietary CDGS and WDGS increased the proportion of conjugated linoleic acids (P < 0.05) and tended to increase C18:3n-3 (P = 0.075) and total polyunsaturated fatty acids (P = 0.060) relative to the CON. Feeding diets containing distillers' grains reduced the lipid and colour stability of fresh beef patties stored in modified atmosphere packs (MAP), with CDGS exhibiting an intermediate effect between CON and WDGS. Diet did not negatively influence the texture profile parameters and eating quality attributes of beef stored in MAP. The inclusion of CDGS or WDGS in supplementary concentrates may improve the fatty acid profile but decreased the shelf-life of beef

The interplay between extrinsic and intrinsic factors in determining migration decisions in brown trout (Salmo trutta): An experimental study

Many species are capable of facultative migration, but the relative roles of extrinsic versus intrinsic factors in generating diverse migratory tactics remain unclear. Here we explore the proximate drivers of facultative migration in brown trout in an experimental laboratory setting. The effects of reduced food, as a putative environmental cue, were examined in two populations: one that exhibits high rates of anadromy (sea-migration) in nature, and one that does not exhibit anadromy in nature. Juveniles derived from wild-caught parents were reared for two years under four environmental treatments: low food in years 1 and 2 (Low-Low); high food in years 1 and 2 (High-High), low food in year 1 and high in year 2 (Low-High), and vice versa (High-Low). Food restriction had a significant effect on migratory tactics, with the frequency of smolts (juveniles choosing migration) highest in the Low-Low treatment in both populations. No individuals became smolts in the High-High treatment, and intermediate smolting rates were observed in the Low-High and High-Low treatments. Higher overall smolting rates in the naturally anadromous population suggested an inherited component to anadromy/migration decisions, but both populations showed variability in migratory tactics. Importantly, some fish from the naturally non-anadromous population became smolts in the experiment, implying the capacity for migration was lying ‘dormant’, but they exhibited lower hypo-osmoregulatory function than smolts from the naturally anadromous population. Tactic frequencies in the naturally anadromous population were more affected by food in the 2nd year, while food in the 1st year appeared more important for the naturally non-anadromous population. Migratory tactics were also related to sex, but underpinned in both sexes by growth in key periods, size and energetic state. Collectively these results reveal how migration decisions are shaped by a complex interplay between extrinsic and intrinsic factors, informing our ability to predict how facultatively migratory populations will respond to environmental change

MinION Analysis and Reference Consortium: Phase 1 data release and analysis

The advent of a miniaturized DNA sequencing device with a high-throughput contextual sequencing capability embodies the next generation of large scale sequencing tools. The MinION™ Access Programme (MAP) was initiated by Oxford Nanopore Technologies™ in April 2014, giving public access to their USB-attached miniature sequencing device. The MinION Analysis and Reference Consortium (MARC) was formed by a subset of MAP participants, with the aim of evaluating and providing standard protocols and reference data to the community. Envisaged as a multi-phased project, this study provides the global community with the Phase 1 data from MARC, where the reproducibility of the performance of the MinION was evaluated at multiple sites. Five laboratories on two continents generated data using a control strain of Escherichia coli K-12, preparing and sequencing samples according to a revised ONT protocol. Here, we provide the details of the protocol used, along with a preliminary analysis of the characteristics of typical runs including the consistency, rate, volume and quality of data produced. Further analysis of the Phase 1 data presented here, and additional experiments in Phase 2 of E. coli from MARC are already underway to identify ways to improve and enhance MinION performance

Reflections on a 'virtual' practice development unit: changing practice through identity development

Aims. This paper draws together the personal thoughts and critical reflections of key people involved in the establishment of a ‘virtual’ practice development unit of clinical nurse specialists in the south of England. Background. This practice development unit is ‘virtual’ in that it is not constrained by physical or specialty boundaries. It became the first group of Trust-wide clinical nurse specialists to be accredited in the UK as a practice development unit in 2004. Design and methods. The local university was asked to facilitate the accreditation process via 11 two-hour audio-recorded learning sessions. Critical reflections from practice development unit members, leaders and university staff were written 12 months after successful accreditation, and the framework of their content analysed. Findings and discussion. Practice development was seen as a way for the clinical nurse specialists to realize their potential for improving patient care by transforming care practice in a collaborative, interprofessional and evolutionary manner. The practice development unit provided a means for these nurses to analyse their role and function within the Trust. Roberts’ identity development model for nursing serves as a useful theoretical underpinning for the reflections contained in this paper. Conclusions. These narratives provide another example of nurses making the effort to shape and contribute to patient care through organizational redesign. This group of nurses began to realize that the structure of the practice development unit process provided them with the means to analyse their role and function within the organization and, as they reflected on this structure, their behaviour began to change. Relevance to clinical practice. Evidence from these reflections supports the view that practice development unit participants have secured a positive and professional identity and are, therefore, better able to improve the patient experience

Bardoxolone Methyl Improves Kidney Function in Patients with Chronic Kidney Disease Stage 4 and Type 2 Diabetes:Post-Hoc Analyses from Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes Study

Background: Increases in measured inulin clearance, measured creatinine clearance, and estimated glomerular filtration rate (eGFR) have been observed with bardoxolone methyl in 7 studies enrolling approximately 2,600 patients with type 2 diabetes (T2D) and chronic kidney disease (CKD). The largest of these studies was Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes (BEACON), a multinational, randomized, double-blind, placebo-controlled phase 3 trial which enrolled patients with T2D and CKD stage 4. The BEACON trial was terminated after preliminary analyses showed that patients randomized to bardoxolone methyl experienced significantly higher rates of heart failure events. We performed post-hoc analyses to characterize changes in kidney func-tion induced by bardoxolone methyl. Methods: Patients in -BEACON (n = 2,185) were randomized 1: 1 to receive oncedaily bardoxolone methyl (20 mg) or placebo. We compared the effects of bardoxolone methyl and placebo on a post-hoc composite renal endpoint consisting of = 30% decline from baseline in eGFR, eGFR <15 mL/min/1.73 m2, and end-stage renal disease (ESRD) events (provision of dialysis or kidney transplantation). Results: Consistent with prior studies, patients randomized to bardoxolone methyl experienced mean increases in eGFR that were sustained through study week 48. Moreover, increases in eGFR from baseline were sustained 4 weeks after cessation of treatment. Patients randomized to bardoxolone methyl were significantly less likely to experience the composite renal endpoint (hazards ratio 0.48 [95% CI 0.36-0.64]; p <0.0001). Conclusions: Bardoxolone methyl preserves kidney function and may delay the onset of ESRD in patients with T2D and stage 4 CKD. (C) 2018 The Author(s) Published by S. Karger AG, Base

A Locus on Chromosome 5 Is Associated with Dilated Cardiomyopathy in Doberman Pinschers

Dilated cardiomyopathy (DCM) is a heterogeneous group of heart diseases with a strong genetic background. Currently, many human DCM cases exist where no causative mutation can be identified. DCM also occurs with high prevalence in several large dog breeds. In the Doberman Pinscher a specific DCM form characterized by arrhythmias and/or echocardiographic changes has been intensively studied by veterinary cardiologists. We performed a genome-wide association study in Doberman Pinschers. Using 71 cases and 70 controls collected in Germany we identified a genome-wide significant association to DCM on chromosome 5. We validated the association in an independent cohort collected in the United Kingdom. There is no known DCM candidate gene under the association signal. Therefore, DCM in Doberman Pinschers offers the chance of identifying a novel DCM gene that might also be relevant for human health

Circulating microRNAs Reveal Time Course of Organ Injury in a Porcine Model of Acetaminophen-Induced Acute Liver Failure

Acute liver failure is a rare but catastrophic condition which can progress rapidly to multi-organ failure. Studies investigating the onset of individual organ injury such as the liver, kidneys and brain during the evolution of acute liver failure, are lacking. MicroRNAs are short, non-coding strands of RNA that are released into the circulation following tissue injury. In this study, we have characterised the release of both global microRNA and specific microRNA species into the plasma using a porcine model of acetaminophen-induced acute liver failure. Pigs were induced to acute liver failure with oral acetaminophen over 19h±2h and death occurred 13h±3h thereafter. Global microRNA concentrations increased 4h prior to acute liver failure in plasma (P<0.0001) but not in isolated exosomes, and were associated with increasing plasma levels of the damage-associated molecular pattern molecule, genomic DNA (P<0.0001). MiR122 increased around the time of onset of acute liver failure (P<0.0001) and was associated with increasing international normalised ratio (P<0.0001). MiR192 increased 8h after acute liver failure (P<0.0001) and was associated with increasing creatinine (P<0.0001). The increase in miR124-1 occurred concurrent with the pre-terminal increase in intracranial pressure (P<0.0001) and was associated with decreasing cerebral perfusion pressure (P<0.002)