VRE acquisition in hospital and its association with hospital antimicrobial usage -a non-linear analysis of an extended time series.

BACKGROUND: Vancomycin resistant enterococci (VRE) have become endemic pathogens in many Australian hospitals causing significant morbidity. There are few observational studies that have evaluated the effect of antibiotic usage on VRE acquisition. This study examined VRE acquisition and its association with antimicrobial use. The setting was a NSW tertiary hospital with 800 beds over a 63 month period up to March 2020, straddling piperacillin-tazobactam (PT) shortages that occurred from in September 2017. METHODS: The primary outcome was monthly inpatient hospital onset Vancomycin-resistant Enterococci (VRE) acquisitions. Multivariate adaptive regression splines (MARS) were used to estimate hypothetical thresholds, where antimicrobial use above threshold is associated with increased incidence of hospital onset VRE acquisition. Specific antimicrobials and categorised usage (broad, less broad and narrow spectrum) were modelled. RESULTS: There were 846 hospital onset VRE detections over the study period. Hospital onset vanB and vanA VRE acquisitions fell significantly by 64% and 36% respectively after the PT shortage. MARS modelling indicated that PT usage was the only antibiotic found to exhibit a meaningful threshold. PT usage greater than 17.4 defined daily doses/1000 occupied bed-days (95%C I: 13.4, 20.5) was associated with higher onset of hospital VRE. CONCLUSIONS: This paper highlights the large, sustained impact that reduced broad spectrum antimicrobial use had on VRE acquisition and showed that PT use in particular was a major driver with a relatively low threshold. It raises the question as to whether hospitals should be determining local antimicrobial usage targets based on direct evidence from local data analysed with non-linear methods.

Modulation, microbiota and inflammation in the adult CF gut: A prospective study.

BACKGROUND: Cystic Fibrosis (CF) has prominent gastrointestinal and pancreatic manifestations. The aim of this study was to determine the effect of Cystic fibrosis transmembrane conductance regulator (CFTR) modulation on, gastrointestinal inflammation, pancreatic function and gut microbiota composition in people with cystic fibrosis (CF) and the G551D-CFTR mutation. METHODS: Fourteen adult patients with the G551D-CFTR mutation were assessed clinically at baseline and for up to 1 year after treatment with ivacaftor. The change in gut inflammatory markers (calprotectin and lactoferrin), exocrine pancreatic status and gut microbiota composition and structure were assessed in stool samples. RESULTS: There was no significant change in faecal calprotectin nor lactoferrin in patients with treatment while all patients remained severely pancreatic insufficient. There was no significant change in gut microbiota diversity and richness following treatment. CONCLUSION: There was no significant change in gut inflammation after partial restoration of CFTR function with ivacaftor, suggesting that excess gut inflammation in CF is multi-factorial in aetiology. In this adult cohort, exocrine pancreatic function was irreversibly lost. Longer term follow-up may reveal more dynamic changes in the gut microbiota and possible restoration of CFTR function.

Healthcare professionals in research (HPiR) Facebook community: a survey of U.K. doctoral and postdoctoral healthcare professionals outside of medicine.

BACKGROUND: Healthcare professionals outside of medicine (HCPs), including nurses, midwives and allied health professionals, are increasingly involved in research for patient benefit. Their challenge is to negotiate inter-professional or professionally isolated contexts. The aims of this study were to evaluate the 'Healthcare Professionals in Research' (HPiR) Facebook group (a self-directed and confidential peer support group for doctoral and postdoctoral HCPs) including engagement, the experiences of doctoral and postdoctoral HPiR members and to identify future career challenges using an on-line survey. METHODS: The HPiR Facebook group was launched in May 2019. Five HCP Community managers (CMs) were trained in on-line platform curation, moderation and screening. An on-line survey was designed to capture data from HPiR members. A purposive sampling approach was applied. Respondents were required to be doctoral and postdoctoral HCPs and a registered member of the HPiR group. Respondents represented a range of healthcare professions, 79 % of whom had over ten years clinical experience. Membership growth and engagement was analysed. Descriptive statistics were used to present numerical data. Qualitative data were analysed thematically. RESULTS: 96 members were admitted to the group within the first month. All members were actively engaged with group content. 34/96 doctoral and postdoctoral HCPs completed the survey. Most members joined for networking (88 %) and peer support (82 %) purposes. Analysis of text responses showed difficulties in balancing a clinical academic career and highlighted the consequences of undefined clinical academic roles and pathways. CONCLUSIONS: Doctoral and postdoctoral HCPs value the opportunities that HPiR provides for peer support and connection with fellow HCPs. HPiR has the potential to strengthen research capacity, support research skill development and drive change within the clinical academic community. Clinical academic roles and pathways need to be standardised. The creation of opportunities beyond doctoral studies is a priority.

How accurately is hospital acquired pneumonia documented for the correct assignment of a hospital acquired complication (HAC)?

BACKGROUND: In 2016, the Australian Commission on Safety and Quality in Healthcare (ACSQHC) released a list of 16 categories of potentially preventable, high impact hospital-acquired complications (HAC) identified by using administrative coded data (ACD). An important category are hospital-acquired infections (HAI). Within this category, hospital-acquired pneumonia (HAP) is among the most frequent complications documented. There are no published studies concerning the current ACSQHC approach to HAI surveillance using ACD and no pneumonia-specific ACD studies reported from Australia. Published work indicates that ACD detection of HAP has low a sensitivity and positive predictive value (PPV). The current study was designed to examine whether coders correctly reflected the documentation of HAP that was present in the medical record and also evaluated the medical documentation that was present. METHODS: One hundred patients with ACD encoded HAP were selected for review, drawn from admissions to 2 Hunter New England Health hospitals during 2017. Patient records and the eMR were reviewed by two medical officers to assess medical and radiological documentation of pneumonia. The district coding manager reviewed the accuracy of coding of a subset of 23 cases where medical review had not located documented evidence of HAP. RESULTS: Of the 100 reviewed cases, the median patient age was 75 years (range 0-95 years) with 3% under 16 years of age. Twenty one were intensive care-associated of which 13 were associated with ventilation. In 23 cases the documentation was disputed and a secondary review took place - the coding manager confirmed coding changes in 14 of these 23 cases. CONCLUSIONS: This study found that administrative coded data of HAP, utilizing the ACSQHC method reliably reflected the available documentation with a PPV of 86% (95% binomial exact confidence interval 77-92%), much higher than documented by previous ACD studies. The actual documentation of pneumonia by medical staff frequently used the non-specific term 'lower respiratory infection (LRTI)' which we recommend to be avoided. Radiological confirmation was absent in one third of cases. We recommend the adoption of a medical note template checklist for HAP to prompt clinicians with the accepted diagnostic criteria. We also recommend documenting a reason as to why any antibiotic has been commenced in a hospitalized patient in accord with the ACSQHC Antimicrobial Stewardship Clinical Care Standard.

Reliability and minimal detectable change of the 'Imperial Spine' marker set for the evaluation of spinal and lower limb kinematics in adults.

OBJECTIVES: As a step towards the comprehensive evaluation of movement in patients with low back pain, the aim of this study is to design a marker set (three rigid segment spine, pelvic and lower limb model) and evaluate the reliability and minimal detectable change (MDC) of this marker set in healthy adults during gait and sit to stand (STS) tasks using three dimensional motion capture. RESULTS: The 'Imperial Spine' marker set was used to assess relative peak angles during gait and STS tasks using the minimum recommended sample size (n = 10) for reliability studies with minimum Intraclass Correlation Coefficient (ICC) of 0.70, optimum ICC 0.90 and 9 trials replicated per subject per task. Intra- and inter-tester reliability between an experienced and inexperienced user was examined. ICC, mean, standard error (SEM), Bland Altman 95% limits of agreement (LOA) and MDC were computed. ICC values demonstrated excellent intra- and inter-tester reliability in both tasks, particularly in the sagittal plane (majority ICCs > 0.80). SEM measurements were lower in gait (0.8-5.5°) than STS tasks (1°-12.6°) as were MDC values. LOA demonstrated good agreement. The 'Imperial Spine' marker set is reliable for use in healthy adults during functional tasks. Future evaluation in patients is required.

The effects of hedgehog ligand neutralising antibody 5E1 in a mouse model of endometriosis.

OBJECTIVE: Endometriosis is a common and painful condition characterised by the formation of endometrial lesions within the peritoneal cavity. Previous studies have suggested a role for hedgehog signalling in the pathogenesis of endometriosis. We investigated the role of hedgehog signalling in the establishment of endometriosis lesions using 5E1, a hedgehog ligand neutralising antibody, and a mouse model of endometriosis. To mimic the initiation of endometriosis by retrograde menstruation, which is believed to occur in humans, donor mice underwent an artificial menstruation protocol. Fragments of menstrual endometrium were injected into the peritoneal cavity of estrogen primed recipients. Recipients received twice weekly injections of 5E1 or an isotype matched control antibody for three weeks. Lesions were collected and analysed for markers of epithelium, proliferation and apoptosis by immunofluorescence microscopy. RESULTS: Treatment with 5E1 reduced the number of lesions found on the mesentery. No significant changes were found in the size of lesions, abundance of endometrial epithelial cells, proliferation or apoptosis.

Least cost energy system pathways towards 100% renewable energy in Ireland by 2050.

Studies focusing on 100% renewable energy systems have emerged in recent years; however, existing studies tend to focus only on the power sector using exploratory approaches. This paper therefore undertakes a whole-system approach and explores optimal pathways towards 100% renewable energy by 2050. The analysis is carried out for Ireland, which currently has the highest share of variable renewable electricity on a synchronous power system. Large numbers of scenarios are developed using the Irish TIMES model to address uncertainties. Results show that compared to decarbonization targets, focusing on renewable penetration without considering carbon capture options is significantly less cost effective in carbon mitigation. Alternative assumptions on bioenergy imports and maximum variability in power generation lead to very different energy mixes in bioenergy and electrification levels. All pathways suggest that indigenous bioenergy needs to be fully exploited and the current annual deployment rate of renewable electricity needs a boost. Pathways relying on international bioenergy imports are slightly cheaper and faces less economic and technical challenges. However, given the large future uncertainties, it is recommended that further policy considerations be given to pathways with high electrification levels as they are more robust towards uncertainties.

Endometrial Mesenchymal Stem/Stromal Cells Modulate the Macrophage Response to Implanted Polyamide/Gelatin Composite Mesh in Immunocompromised and Immunocompetent Mice.

The immunomodulatory properties of human endometrial mesenchymal stem cells (eMSC) have not been well characterised. Initial studies showed that eMSC modulated the chronic inflammatory response to a non-degradable polyamide/gelatin mesh in a xenogeneic rat skin wound repair model, but the mechanism remains unclear. In this study, we investigated the immunomodulatory effect of eMSC on the macrophage response to polyamide/gelatin composite mesh in an abdominal subcutaneous wound repair model in C57BL6 immunocompetent and NSG (NOD-Scid-IL2Rgamma null ) immunocompromised mice to determine whether responses differed in the absence of an adaptive immune system and NK cells. mCherry lentivirus-labelled eMSC persisted longer in NSG mice, inducing longer term paracrine effects. Inclusion of eMSC in the mesh reduced inflammatory cytokine (Il-1ß, Tnfα) secretion, and in C57BL6 mice reduced CCR7+ M1 macrophages surrounding the mesh on day 3 and increased M2 macrophage marker mRNA (Arg1, Mrc1, Il10) expression at days 3 and 7. In NSG mice, these effects were delayed and only observed at days 7 and 30 in comparison with controls implanted with mesh alone. These results show that the differences in the immune status in the two animals directly affect the survival of xenogeneic eMSC which leads to differences in the short-term and long-term macrophage responses to implanted meshes.

A survey to determine usual care after cancer treatment within the United Kingdom national health service.

BACKGROUND: Approximately one third of cancer survivors in the United Kingdom face ongoing and debilitating psychological and physical symptoms related to poor quality of life. Very little is known about current post-cancer treatment services. METHODS: Oncology healthcare professionals (HCPs) were invited to take part in a survey, which gathered both quantitative and free text data about the content and delivery of cancer aftercare and patient needs. Analysis involved descriptive statistics and content analysis. RESULTS: There were 163 complete responses from 278 survey participants; 70% of NHS acute trusts provided data. HCPs views on patient post-cancer treatment needs were most frequently: fear of recurrence (95%), fatigue (94%), changes in physical capabilities (89%), anxiety (89%) and depression (88%). A median number of 2 aftercare sessions were provided (interquartile range: 1,4) lasting between 30 and 60 min. Usually these were provided face-to-face and intermittently by a HCP. However, sessions did not necessarily address the issues HCPs asserted as important. Themes from free-text responses highlighted inconsistencies in care, uncertain funding for services and omission of some evidence based approaches. CONCLUSION: Provision of post-cancer treatment follow-up care is neither universal nor consistent in the NHS, nor does it address needs HCPs identified as most important.

Mesenchymal stem/stromal cells in post-menopausal endometrium.

STUDY QUESTION: Does post-menopausal endometrium contain mesenchymal stem/stromal cells (MSC) that have adult stem cell properties and can be prospectively isolated from a biopsy? SUMMARY ANSWER: Perivascular W5C5(+) cells isolated from post-menopausal endometrial biopsies displayed characteristic MSC properties of clonogenicity, multipotency and surface phenotype irrespective of whether the women were or were not pre-treated with estrogen to regenerate the endometrium. WHAT IS KNOWN ALREADY: Recently MSCs have been identified in human premenopausal endometrium, and can be prospectively isolated using a single marker, W5C5/SUSD2. STUDY DESIGN, SIZE, DURATION: Endometrial tissue of both the functional and basal layers, from 17 premenopausal (pre-MP) women, 19 post-menopausal (post-MP) women without hormonal treatment and 15 post-menopausal women on estrogen replacement therapy (post-MP+ E2), was collected through a prospective phase IV clinical trial over 2 years. PARTICIPANTS/MATERIALS, SETTING, METHODS: Post-menopausal women <65 years of age were treated with or without E2 for 6-8 weeks prior to tissue collection. Serum E2 levels were determined by estradiol immunoenzymatic assay. Endometrial tissue was obtained from women by biopsy (curettage) just prior to the hysterectomy. The effect of E2 on endometrial thickness and glandular and luminal epithelial height was determined using image analysis. Endometrial tissue was dissociated into single cell suspensions and MSC properties were examined in freshly isolated and short-term cultured, magnetic bead-purified W5C5(+) cells. MSC properties were assessed using clonogenicity, serial cloning, mesodermal differentiation in adipogenic, chondrogenic, osteogenic and myogenic induction culture media, and surface phenotype analysis by flow cytometry. Estrogen receptor α expression in W5C5(+) cells was examined using dual colour immunofluorescence. Vascularity was analysed using CD34 and alpha smooth muscle actin immunostaining and subsequent image analysis. MAIN RESULTS AND THE ROLE OF CHANCE: A small population of stromal cells with MSC properties was purified with the W5C5 antibody from post-menopausal endometrium, whether atrophic from low circulating estrogen or regenerated from systemic estrogen treatment, similar to premenopausal endometrium. The MSC derived from post-menopausal endometrium treated with or without E2 fulfilled the minimum MSC criteria: clonogenicity, surface phenotype (CD29(+), CD44(+), CD73(+), CD105(+), CD140b(+), CD146(+)) and multipotency. The post-menopausal endometrial MSCs also showed comparable properties to premenopausal eMSC with respect to self-renewal in vitro and W5C5 expression. The W5C5(+) cells were located perivascularly as expected and did not express estrogen receptor α. LIMITATIONS, REASONS FOR CAUTION: The properties of the MSC derived from post-menopausal endometrium were evaluated in vitro and their in vivo tissue reconstitution capacity has not been established as it has for premenopausal endometrial MSC. WIDER IMPLICATIONS OF THE FINDINGS: The endometrium is an accessible source of MSC obtainable with minimum morbidity that could be used for future clinical applications as a cell-based therapy. This study shows that menopausal women can access their endometrial MSC by a simple biopsy for use in autologous therapies, particularly if their endometrium has been regenerated by short-term E2 treatment, provided they have an intact uterus and are not contraindicated for short-term E2 treatment. Endometrial MSC in post-menopausal women possess key MSC properties and are a promising source of MSC independent of a woman's age. STUDY FUNDING/COMPETING INTERESTS: This study was supported by the National Health and Medical Research Council (NHMRC) of Australia grant (1021126) (C.E.G., A.R.) and Senior Research Fellowship (1042298) (C.E.G.), Australian Gynaecological Endoscopic Society grant (A.R.) , Monash International Postgraduate Research Scholarship (DU), Australian Stem Cell Centre, South East Melbourne Alliance for Regenerative Therapies and Australian Stem Cell Centre top up scholarships (DU) and Victorian Government's Operational Infrastructure Support Program. Competing interests: AR receives Preceptorship fees from AMS, advisory board fees and sponsored study from Astellas, and conducts investigator led studies sponsored by AMS and Boston Scientific for other projects. TRIAL REGISTRATION NUMBER: CTNRN12610000563066.

In vitro activity of CEM-102 (fusidic acid) against prevalent clones and resistant phenotypes of Staphylococcus aureus.

Clinical development of CEM-102 (fusidic acid) has recently begun in the United States for chronic oral treatment of prosthetic joint infections. To support this development, the in vitro activity of fusidic acid against important Staphylococcus aureus clones and resistance phenotypes was determined. Against 51 such isolates, the modal fusidic acid MIC was 0.12 µg/ml (range, 0.06 to 0.25 µg/ml for 49 isolates). This level of in vitro fusidic acid activity underscores the potential clinical utility of this compound in the United States.

Bilateral rubeosis iridis and rubeotic glaucoma due to peripheral occlusive vasculitis associated with multiple sclerosis.

UNLABELLED: Multiple sclerosis is associated with iridocyclitis, intermediate uveitis, retinal periphlebitis, and optic neuritis. The periphlebitis is known to be rarely sight-threatening as a result of the sequelae of retinal neovascularization. CASE: This is a rare case of bilateral rubeosis iridis and rubeotic glaucoma in the setting of a branch retinal vein occlusion, widespread peripheral periphlebitis, and angiographic peripheral closure associated with "clinically definite" multiple sclerosis. DISCUSSION: The case illustrates the extreme end of the spectrum of peripheral retinal ischemia and neovascularization associated with demyelinating disease, which can present as rubeotic glaucoma. Such patients require a proactive approach to inflammation, neovascularization, and raised intraocular pressure, including systemic immunosuppression, photocoagulation, and augmented trabeculectomy, respectively. As with other causes of peripheral ischemia, a favorable visual outcome can often be achieved using this strategy.

Free carrier lifetime modification for silicon waveguide based devices.

We investigate the effect of silicon ion irradiation on free carrier lifetime in silicon waveguides, and thus its ability to reduce the density of two-photon-absorption (TPA) generated free carriers. Our experimental results show that free carrier lifetime can be reduced significantly by silicon ion implantation. Associated excess optical absorption from the implanted ions can be reduced to an acceptable level if irradiation energy and dose are correctly chosen. Simulations of Raman scattering suggest that net gain can be achieved in certain cases without the need for an integrated diode in reverse bias to remove the photo-generated free carriers.