Emergency supply of prescription-only medicines to patients by community pharmacists: a mixed methods evaluation incorporating patient, pharmacist and GP perspectives

Objective To evaluate and inform emergency supply of prescription-only medicines by community pharmacists (CPs), including how the service could form an integral component of established healthcare provision to maximise adherence. Design Mixed methods. 4 phases: prospective audit of emergency supply requests for prescribed medicines (October–November 2012 and April 2013); interviews with CPs (February–April 2013); follow-up interviews with patients (April–May 2013); interactive feedback sessions with general practice teams (October–November 2013). Setting 22 community pharmacies and 6 general practices in Northwest England. Participants 27 CPs with experience of dealing with requests for emergency supplies; 25 patients who received an emergency supply of a prescribed medicine; 58 staff at 6 general practices. Results Clinical audit in 22 pharmacies over two 4-week periods reported that 526 medicines were requested by 450 patients. Requests peaked over a bank holiday and around weekends. A significant number of supplies were made during practice opening hours. Most requests were for older patients and for medicines used in long-term conditions. Difficulty in renewing repeat medication (forgetting to order, or prescription delays) was the major reason for requests. The majority of medicines were ‘loaned’ in advance of a National Health Service (NHS) prescription. Interviews with CPs and patients indicated that continuous supply had a positive impact on medicines adherence, removing the need to access urgent care. General practice staff were surprised and concerned by the extent of emergency supply episodes. Conclusions CPs regularly provide emergency supplies to patients who run out of their repeat medication, including during practice opening hours. This may aid adherence. There is currently no feedback loop, however, to general practice. Patient care and interprofessional communication may be better served by the introduction of a formally structured and funded NHS emergency supply service from community pharmacies, with ongoing optimisation of repeat prescribing

Identification of systemic immune response markers through metabolomic profiling of plasma from calves given an intra-nasally delivered respiratory vaccine

International audienceVaccination procedures within the cattle industry are important disease control tools to minimize economic and welfare burdens associated with respiratory pathogens. However, new vaccine, antigen and carrier technologies are required to combat emerging viral strains and enhance the efficacy of respiratory vaccines, particularly at the point of pathogen entry. New technologies, specifically metabolomic profiling, could be applied to identify metabolite immune-correlates representative of immune protection following vaccination aiding in the design and screening of vaccine candidates. This study for the first time demonstrates the ability of untargeted UPLC-MS metabolomic profiling to identify metabolite immune correlates characteristic of immune responses following mucosal vaccination in calves. Male Holstein Friesian calves were vaccinated with Pfizer Rispoval® PI3 + RSV intranasal vaccine and metabolomic profiling of post-vaccination plasma revealed 12 metabolites whose peak intensities differed significantly from controls. Plasma levels of glycocholic acid, N-[(3α,5β,12α)-3,12-Dihydroxy-7,24-dioxocholan-24-yl]glycine, uric acid and biliverdin were found to be significantly elevated in vaccinated animals following secondary vaccine administration, whereas hippuric acid significantly decreased. In contrast, significant upregulation of taurodeoxycholic acid and propionylcarnitine levels were confined to primary vaccine administration. Assessment of such metabolite markers may provide greater information on the immune pathways stimulated from vaccine formulations and benchmarking early metabolomic responses to highly immunogenic vaccine formulations could provide a means for rapidly assessing new vaccine formulations. Furthermore, the identification of metabolic systemic immune response markers which relate to specific cell signaling pathways of the immune system could allow for targeted vaccine design to stimulate key pathways which can be assessed at the metabolic level

HIV type 1 subtype C gag and nef diversity in Southern Africa.

Several HIV-1 subtype C-specific gag- and/or nef-based vaccines are currently intended for clinical trial in southern Africa. Here we provide sequences of 64 gag and 45 nef genes sampled in Malawi, Zambia, Zimbabwe, and South Africa and assess the degree of southern African HIV-1 diversity that will confront these vaccines. Whereas reasonable phylogenetic evidence exists for geographical clustering of subtype C gag and nef sequences from various other parts of the world, there is little evidence of similar population founder effects in the southern African epidemic. The entire breadth of subtype C diversity is represented in the southern African genes suggesting there may be no advantage in producing region- or country-specific subtype C vaccines. We do not, however, find much evidence of intersubtype recombination in the Southern African genes, implying that the likelihood of vaccine failure due to the emergence of intersubtype recombinants is probably low

A large proportion of asymptomatic Plasmodium infections with low and sub-microscopic parasite densities in the low transmission setting of Temotu Province, Solomon Islands: challenges for malaria diagnostics in an elimination setting

Background: Many countries are scaling up malaria interventions towards elimination. This transition changes demands on malaria diagnostics from diagnosing ill patients to detecting parasites in all carriers including asymptomatic infections and infections with low parasite densities. Detection methods suitable to local malaria epidemiology must be selected prior to transitioning a malaria control programme to elimination. A baseline malaria survey conducted in Temotu Province, Solomon Islands in late 2008, as the first step in a provincial malaria elimination programme, provided malaria epidemiology data and an opportunity to assess how well different diagnostic methods performed in this setting

Direct correlation between potentiometric and impedance biosensing of antibody-antigen interactions using an integrated system

A fully integrated system that combines extended gate field-effect transistor (EGFET)-based potentiometric biosensors and electrochemical impedance spectroscopy (EIS)-based biosensors has been demonstrated. This integrated configuration enables the sequential measurement of the same immunological binding event on the same sensing surface and consequently sheds light on the fundamental origins of sensing signals produced by FET and EIS biosensors, as well as the correlation between the two. Detection of both the bovine serum albumin (BSA)/anti-BSA model system in buffer solution and bovine parainfluenza antibodies in complex blood plasma samples was demonstrated using the integrated biosensors. Comparison of the EGFET and EIS sensor responses reveals similar dynamic ranges, while equivalent circuit modeling of the EIS response shows that the commonly reported total impedance change (DZtotal) is dominated by the change in charge transfer resistance (Rct) rather than surface capacitance (Csurface). Using electrochemical kinetics and the Butler-Volmer equation, we unveil that the surface potential and charge transfer resistance, measured by potentiometric and impedance biosensors, respectively, are, in fact, intrinsically linked. This observation suggests that there is no significant gain in using the FET/EIS integrated system and leads to the demonstration that low-cost EGFET biosensors are sufficient as a detection tool to resolve the charge information of biomolecules for practical sensing applications

DIVA metabolomics: Differentiating vaccination status following viral challenge using metabolomic profiles

Publication history: Accepted - 5 March 2018; Published online - 4 April 2018Bovine Respiratory Disease (BRD) is a major source of economic loss within the agricultural industry. Vaccination against BRD-associated viruses does not offer complete immune protection and vaccine failure animals present potential routes for disease spread. Serological differentiation of infected from vaccinated animals (DIVA) is possible using antigen-deleted vaccines, but during virus outbreaks DIVA responses are masked by wild-type virus preventing accurate serodiagnosis. Previous work by the authors has established the potential for metabolomic profiling to reveal metabolites associated with systemic immune responses to vaccination. The current study builds on this work by demonstrating for the first time the potential to use plasma metabolite profiling to differentiate between vaccinated and non-vaccinated animals following infection-challenge. Male Holstein Friesian calves were intranasally vaccinated (Pfizer RISPOVAL®PI3+RSV) and subsequently challenged with Bovine Parainfluenza Virus type-3 (BPI3V) via nasal inoculation. Metabolomic plasma profiling revealed that viral challenge led to a shift in acquired plasma metabolite profiles from day 2 to 20 p.i., with 26 metabolites identified whose peak intensities were significantly different following viral challenge depending on vaccination status. Elevated levels of biliverdin and bilirubin and decreased 3-indolepropionic acid in non-vaccinated animals at day 6 p.i. may be associated with increased oxidative stress and reactive oxygen scavenging at periods of peak virus titre. During latter stages of infection, increased levels of N-[(3α,5β,12α)-3,12-dihydroxy-7,24-dioxocholan-24-yl]glycine and lysophosphatidycholine and decreased enterolactone in non-vaccinated animals may reflect suppression of innate immune response mechanisms and progression to adaptive immune responses. Levels of hexahydrohippurate were also shown to be significantly elevated in non-vaccinated animals from days 6 to 20 p.i. These findings demonstrate the potential of metabolomic profiling to identify plasma markers that can be employed in disease diagnostic applications to both differentially identify infected non-vaccinated animals during disease outbreaks and provide greater information on the health status of infected animals.This research was funded by a Department of Agriculture and Rural Development (DARD) Northern Ireland postgraduate studentship awarded to Darren Gra

Pathological and Phylogenetic characterisation of Amphibiothecum sp. infection in an isolated amphibian (Lissotriton helveticus) population on the island of Rum (Scotland)

Outbreaks of cutaneous infectious disease in amphibians are increasingly being attributed to an overlooked group of fungal-like pathogens, the Dermocystids. During the last 10 years on the Isle of Rum, Scotland, palmate newts (Lissotriton helveticus) have been reportedly afflicted by unusual skin lesions. Here we present pathological and molecular findings confirming that the pathogen associated with these lesions is a novel organism of the order Dermocystida, and represents the first formally reported, and potentially lethal, case of amphibian Dermocystid infection in the UK. Whilst the gross pathology and the parasite cyst morphology were synonymous to those described in a study from infectedL. helveticusin France, we observed a more extreme clinical outcome on Rum involving severe subcutaneous oedema. Phylogenetic topologies supported synonymy between Dermocystid sequences from Rum and France and as well as their distinction fromAmphibiocystidiumspp. Phylogenetic analysis also suggested that the amphibian-infecting Dermocystids are not monophyletic. We conclude that theL. helveticus-infecting pathogen represents a single, novel species;Amphibiothecum meredithae

A genome-wide investigation of adaptive signatures in protein-coding genes related to tool behaviour in New Caledonian and Hawaiian crows

Funding: A David Phillips Fellowship to C.R. from the UK’s Biotechnology and Biological Sciences Research Council (BBSRC; grant BB/G023913/2). Further funding for personnel and data generation of the remaining species was provided by the European Research Council (ERCStG-336536 FuncSpecGen to J.B.W.W.), the Swedish Research Council Vetenskapsrådet (621-2013-4510 to J.B.W.W.), the Knut and Alice Wallenberg Foundation (to J.B.W.W.), the Lawski foundation (to V.E.K. and J.B.W.W.) and the German Research Foundation (KU 3402/1-1 to V.E.K.). A Marsden Fund Grant to G.R.H., R.D.G. and N.J.G. from the Royal Society of New Zealand (UOA1208), a Japanese Society for Promotion of Science Postdoctoral Fellowship (H.A.), together with funding from University of Auckland (G.R.H. and R.D.G.), the Department of Linguistic and Cultural Evolution at the Max Planck Institute for the Science of Human History, and University of Otago (N.J.G.). N.D. acknowledges funding from the Swiss National Science Foundation (P2SKP3_165031 and P300PA_177845) and the Carl Tryggers Foundation.Very few animals habitually manufacture and use tools. It has been suggested that advanced tool behaviour co-evolves with a suite of behavioural, morphological and life-history traits. In fact, there are indications for such an adaptive complex in tool-using crows (genus Corvus species). Here, we sequenced the genomes of two habitually tool-using and ten non-tool-using crow species to search for genomic signatures associated with a tool-using lifestyle. Using comparative genomic and population genetic approaches, we screened for signals of selection in protein-coding genes in the tool-using New Caledonian and Hawaiian crows. While we detected signals of recent selection in New Caledonian crows near genes associated with bill morphology, our data indicate that genetic changes in these two lineages are surprisingly subtle, with little evidence at present for convergence. We explore the biological explanations for these findings, such as the relative roles of gene regulation and protein-coding changes, as well as the possibility that statistical power to detect selection in recently diverged lineages may have been insufficient. Our study contributes to a growing body of literature aiming to decipher the genetic basis of recently evolved complex behaviour.PostprintPeer reviewe