Specialist tissue viability services: a priority or a luxury?

During the 1980s, the number of tissue viability nurses (TVNs) rose steadily in the UK, in response to mismanagement of patients with wounds (Fletcher, 1995). Since this time, and in response to the quality agenda, the necessity of promoting a tissue viability service (TVS) that is able to meet the needs of a changing population, while being cost effective and offering interventions based on research and evidence, has grown. The drive to reduce avoidable harm in healthcare and to make efficiency savings is continuing, with TVS being one of the key areas to deliver these targets. However, across the UK we have a wide range of role descriptions and job titles, yet little clarification as to the qualifications and skills required to deliver a successful TVS. Infection control specialist nurses have a clear identity with concise role descriptions representing a range of pay bands. Arguably, this is because they are aligned with a medical specialty, whereas TV is not. The introduction of ‘Any Qualified Provider’ (Department of Health, 2011) has witnessed some services, including management of leg ulceration, being delivered by non-NHS providers at a reduced cost. So is TVS in danger of becoming more of a ‘nice thing’ rather than a priority

A One Health investigation of Salmonella enterica serovar Wangata in north-eastern New South Wales, Australia, 2016-2017

Salmonella enterica serovar Wangata (S. Wangata) is an important cause of endemic salmonellosis in Australia, with human infections occurring from undefined sources. This investigation sought to examine possible environmental and zoonotic sources for human infections with S. Wangata in north-eastern New South Wales (NSW), Australia. The investigation adopted a One Health approach and was comprised of three complimentary components: a case–control study examining human risk factors; environmental and animal sampling; and genomic analysis of human, animal and environmental isolates. Forty-eight human S. Wangata cases were interviewed during a 6-month period from November 2016 to April 2017, together with 55 Salmonella Typhimurium (S. Typhimurium) controls and 130 neighbourhood controls. Indirect contact with bats/flying foxes (S. Typhimurium controls (adjusted odds ratio (aOR) 2.63, 95% confidence interval (CI) 1.06–6.48)) (neighbourhood controls (aOR 8.33, 95% CI 2.58–26.83)), wild frogs (aOR 3.65, 95% CI 1.32–10.07) and wild birds (aOR 6.93, 95% CI 2.29–21.00) were statistically associated with illness in multivariable analyses. S. Wangata was detected in dog faeces, wildlife scats and a compost specimen collected from the outdoor environments of cases’ residences. In addition, S. Wangata was detected in the faeces of wild birds and sea turtles in the investigation area. Genomic analysis revealed that S. Wangata isolates were relatively clonal. Our findings suggest that S. Wangata is present in the environment and may have a reservoir in wildlife populations in north-eastern NSW. Further investigation is required to better understand the occurrence of Salmonella in wildlife groups and to identify possible transmission pathways for human infections.Whole genome sequencing for this project was supported by the NSW Public Health Pathogen Genomics Consortium, CIDM-PH, NSW Health

Genomic Epidemiology of Complex, Multispecies, Plasmid-Borne bla KPC Carbapenemase in Enterobacterales in the United Kingdom from 2009 to 2014.

Carbapenem resistance in Enterobacterales is a public health threat. Klebsiella pneumoniae carbapenemase (encoded by alleles of the bla KPC family) is one of the most common transmissible carbapenem resistance mechanisms worldwide. The dissemination of bla KPC historically has been associated with distinct K. pneumoniae lineages (clonal group 258 [CG258]), a particular plasmid family (pKpQIL), and a composite transposon (Tn4401). In the United Kingdom, bla KPC has represented a large-scale, persistent management challenge for some hospitals, particularly in North West England. The dissemination of bla KPC has evolved to be polyclonal and polyspecies, but the genetic mechanisms underpinning this evolution have not been elucidated in detail; this study used short-read whole-genome sequencing of 604 bla KPC-positive isolates (Illumina) and long-read assembly (PacBio)/polishing (Illumina) of 21 isolates for characterization. We observed the dissemination of bla KPC (predominantly bla KPC-2; 573/604 [95%] isolates) across eight species and more than 100 known sequence types. Although there was some variation at the transposon level (mostly Tn4401a, 584/604 [97%] isolates; predominantly with ATTGA-ATTGA target site duplications, 465/604 [77%] isolates), bla KPC spread appears to have been supported by highly fluid, modular exchange of larger genetic segments among plasmid populations dominated by IncFIB (580/604 isolates), IncFII (545/604 isolates), and IncR (252/604 isolates) replicons. The subset of reconstructed plasmid sequences (21 isolates, 77 plasmids) also highlighted modular exchange among non-bla KPC and bla KPC plasmids and the common presence of multiple replicons within bla KPC plasmid structures (>60%). The substantial genomic plasticity observed has important implications for our understanding of the epidemiology of transmissible carbapenem resistance in Enterobacterales for the implementation of adequate surveillance approaches and for control

Systems and people under pressure : the discharge process in an acute hospital

Aims.  To understand the perspective of hospital-based health professionals with regard to preparing patients for discharge from an acute hospital in England. Background.  The hospital experience in England over recent years is characterised by increasing admission rates and decreasing length of stay. Legislation and policy initiatives have also focussed upon the need to reduce delayed discharges. Discharge preparation is known to be a complex intervention with multiple obstacles within and outside of the hospital setting. Design.  Qualitative. Methods.  Posters were displayed within a hospital asking health professionals to take part in a focus group. Maximum variation, in terms of job titles, was sought for within the sample. Focus groups were held in December 2006. Six senior members of staff divided into pairs to run them. All groups were taped and transcribed verbatim and analysed using a framework approach. Results.  Three focus groups were conducted, which involved 11 nurses, 15 allied health professionals, five social workers and one doctor. Analysis identified the following themes and sub themes: 1  Conflicting pressures on staff: •    Keeping patients in hospital vs. getting them out; •    Striving for flexibility within a system; •    A paucity of intermediary provision. 2  Casualties arising from conflicting pressures: •    Professionals losing their sense of professionalism; •    Patients being ‘systematised’. Conclusions.  Pressures described during focus groups stemmed from five main sources: external targets placed upon the system, internal hospital inflexibility and poor communication, the dominance of the medical model of care, a desire to address the complex needs of individuals and a lack of community services. Staff felt themselves to be victims of these competing pressures and that many of the solutions were beyond their influence. Staff described the dehumanising effect of sometimes having to ignore patient concerns, wishes and choices

Genomic characterisation of Salmonella enterica serovar Wangata isolates obtained from different sources reveals low genomic diversity

Salmonella enterica serovar Wangata is an important pathogen in New South Wales (NSW), Australia. The incidence of S. Wangata is increasing and transmission is suspected to be via a non-food source. A recent outbreak investigation of sources of S. Wangata recovered isolates from humans, domestic animals, wildlife and the environment. Here, we extend that investigation by characterising and describing the genomic determinates of these isolates. We found that Australian S. Wangata isolates from different sources exhibited similar virulence and antimicrobial resistance gene profiles. There were no major genomic differences between isolates obtained from different geographical regions within Australia or from different host species. In addition, we found evidence (low number of SNPs and identical virulence gene profiles) suggestive of an international transmission event between Australia and the United Kingdom. This study supports the hypothesis that S. Wangata is shared between different hosts in NSW, Australia and provides strong justification for the continued use of genomic surveillance of Salmonella.This project was supported by funding from the NSW Public Health Pathogen Genomics Consortium, CIDM-PH, NSW Health and seed funding from the Marie Bashir Institute for Infectious Diseases and Biosecurity, The University of Sydne

o-BF3-Phosphonium pincer moieties in the design of delocalized lipophilic cation based tracers for PET imaging of mitochondrial function

International audienceObjectives: Delocalized lipophilic cations, such as triphenylphosphonium (TPP), are able to cross cell membranes and are known to accumulate in the mitochondria in a membrane potential (MMP) dependent manner. MMP is a reliable indicator of mitochondrial and, consequently, cell and tissue function, hence MMP dependent uptake radiotracers are of interest in cardiac and tumour imaging. Conventional C-18F radiofluorination methods require strict aprotic conditions and heating, moreover, C-18F fluorinated tracers may suffer from metabolic defluorination reducing the quality of the images. The objective of this study was to investigate a suitability of o-B[18F]F3-phosphonium pincer moiety, easily accessible via radiofluorination of boronic ester precursors in aqueous mixtures to give high stability, for use as MMP dependent tracers.Methods: Required boronic ester precursors and cold 19F-fluorine labelled reference compounds 1-4 (Fig. 1) were prepared and purified following modified published synthetic protocols. Radiofluorination was carried out in a 0.2 mg scale with carrier added 18F-fluoride at 55oC in 30 min in 20% acetonitrile / water mixture acidified by addition of concentrated hydrochloric acid. LogD7.4 values were determined via the shake flask method. Stability in human serum was assessed using radio-HPLC analysis. The isolated mitochondria uptake assay was performed on freshly isolated mitochondria from Sprague-Dawley rat heart tissue. Cell uptake of the tracer was measured in normal H9c2 cardiac and U87 tumour cells in presence and absence of a membrane depolarizing agent 2-[2-(3-chlorophenyl)hydrazineylyidene]propanedinitrile (CCCP). PET/CT imaging and biodistribution studies were performed in CD-1 nude mice bearing U87 tumour xenografts. Overall charge distributions were calculated using fully optimised geometries at TPSS-D3/def2-TZVPP theory level. 18FHTP (6-18F-fluorohexyltriphenylphosphonium) was prepared in an original one step radiolabelling procedure from an iodinated precursor and was used to validate all assays and as a benchmark for the novel tracers.Results: 18FHTP and 18F-1-4 were obtained in 20-25% decay corrected radiochemical yields within 60 min from the end of bombardment. The LogD7.4 values ranged between 1.78±0.06 (18FHTP and 18F-2) and 0.52±0.01 (18F-1), with 0.88±0.09 and 1.11±0.08 for 18F-3 and 18F-4, respectively. All radiotracers showed 蠅 95% stability in human serum for 3 h. Tracers 18FHTP and 18F-2 showed a comparable MMP dependent uptake in isolated mitochondria (~8%), with the uptake of 18F-3 and 18F-4 below 4% and MMP independent, indicating the importance of the lipophilicity. U87 cell uptake of all tracers was low and MMP independent (~ 0.1% and 1% for 18FHTP and 18F-1-4 respectively). 18F-2 showed the highest and the only MMP dependent cell uptake from the series of new compounds(~ 4% vs ~7% observed for 18FHTP). None of BF3 group containing tracers showed any cardiac or tumour uptake in vivo. Overall charge distribution analysis in a computational study revealed a localised positive charge at the boron atom with partial negative charges carried by fluorine atoms or an ipso carbon of one of the unsubstituted phenyl rings.Conclusion: A series of o-BF3 substituted triphenylphosphonium tracers were successfully synthesized and radiolabelled with fluorine-18. A preliminary in vitro investigation confirmed the importance of the lipophilicity for mitochondrial uptake of the tracer, however, this was not sufficient to ensure cell membrane transport and consequent in vivo localization. The comparison of overall charge distribution maps suggests that addition of a BF3 group introduces a localized charge which is not compensated for by the charge of phosphonium and cannot be delocalised into the phenyl rings