Screening, isolation, and decolonisation strategies in the control of meticillin resistant Staphylococcus aureus in intensive care units: cost effectiveness evaluation

Objective To assess the cost effectiveness of screening, isolation, and decolonisation strategies in the control of meticillin resistant Staphylococcus aureus (MRSA) in intensive care units

The projected effectiveness of Clostridium difficile vaccination as part of an integrated infection control strategy.

BACKGROUND: Early clinical trials of a Clostridium difficile toxoid vaccine show efficacy in preventing C. difficile infection (CDI). The optimal patient group to target for vaccination programmes remains unexplored. This study performed a model-based evaluation of the effectiveness of different CDI vaccination strategies, within the context of existing infection prevention and control strategies such as antimicrobial stewardship. METHODS: An individual-based transmission model of CDI in a high-risk hospital setting was developed. The model incorporated data on patient movements between the hospital, and catchment populations from the community and long-term care facilities (LTCF), using English national and local level data for model-parameterisation. We evaluated vaccination of: (1) discharged patients who had an CDI-occurrence in the ward; (2) LTCF-residents; (3) Planned elective surgical admissions and (4) All three strategies combined. RESULTS: Without vaccination, 10.9 [Interquartile range: 10.0-11.8] patients per 1000 ward admissions developed CDI, of which 31% were ward-acquired. Immunising all three patient groups resulted in a 43% [42-44], reduction of ward-onset CDI on average. Among the strategies restricting vaccination to one target group, vaccinating elective surgical patients proved most effective (35% [34-36] reduction), but least efficient, requiring 146 [133-162] courses to prevent one ICU-onset case. Immunising LTCF residents was most efficient, requiring just 13 [11-16] courses to prevent one case, but considering this only comprised a small group of our hospital population, it only reduced ICU-onset CDI by 9% [8-11]. Vaccination proved most efficient when ward-based transmission rates and antimicrobial consumption were high. CONCLUSIONS: Strategy success depends on the interaction between hospital and catchment populations, and importantly, consideration of importations of CDI from outside the hospital which we found to substantially impact hospital dynamics. Vaccination may be most desirable in settings or patient groups where levels of broad-spectrum antimicrobial use are high and difficult to reduce

Investigating Bacterial Sources of Toxicity as an Environmental Contributor to Dopaminergic Neurodegeneration

Parkinson disease (PD) involves progressive neurodegeneration, including loss of dopamine (DA) neurons from the substantia nigra. Select genes associated with rare familial forms of PD function in cellular pathways, such as the ubiquitin-proteasome system (UPS), involved in protein degradation. The misfolding and accumulation of proteins, such as α-synuclein, into inclusions termed Lewy Bodies represents a clinical hallmark of PD. Given the predominance of sporadic PD among patient populations, environmental toxins may induce the disease, although their nature is largely unknown. Thus, an unmet challenge surrounds the discovery of causal or contributory neurotoxic factors that could account for the prevalence of sporadic PD. Bacteria within the order Actinomycetales are renowned for their robust production of secondary metabolites and might represent unidentified sources of environmental exposures. Among these, the aerobic genera, Streptomyces, produce natural proteasome inhibitors that block protein degradation and may potentially damage DA neurons. Here we demonstrate that a metabolite produced by a common soil bacterium, S. venezuelae, caused DA neurodegeneration in the nematode, Caenorhabditis elegans, which increased as animals aged. This metabolite, which disrupts UPS function, caused gradual degeneration of all neuronal classes examined, however DA neurons were particularly vulnerable to exposure. The presence of DA exacerbated toxicity because neurodegeneration was attenuated in mutant nematodes depleted for tyrosine hydroxylase (TH), the rate-limiting enzyme in DA production. Strikingly, this factor caused dose-dependent death of human SH-SY5Y neuroblastoma cells, a dopaminergic line. Efforts to purify the toxic activity revealed that it is a highly stable, lipophilic, and chemically unique small molecule. Evidence of a robust neurotoxic factor that selectively impacts neuronal survival in a progressive yet moderate manner is consistent with the etiology of age-associated neurodegenerative diseases. Collectively, these data suggest the potential for exposures to the metabolites of specific common soil bacteria to possibly represent a contributory environmental component to PD

Patents and Industrialisation. An Historical Overview of the British Case, 1624-1907

A Report to the Strategic Advisory Board on Intellectual Property Policy (SABIP), U

The Feedback Intervention Trial (FIT)--improving hand-hygiene compliance in UK healthcare workers: a stepped wedge cluster randomised controlled trial.

Achieving a sustained improvement in hand-hygiene compliance is the WHO's first global patient safety challenge. There is no RCT evidence showing how to do this. Systematic reviews suggest feedback is most effective and call for long term well designed RCTs, applying behavioural theory to intervention design to optimise effectiveness

Identification of novel risk loci, causal insights, and heritable risk for Parkinson's disease: a meta-analysis of genome-wide association studies

Background Genome-wide association studies (GWAS) in Parkinson's disease have increased the scope of biological knowledge about the disease over the past decade. We aimed to use the largest aggregate of GWAS data to identify novel risk loci and gain further insight into the causes of Parkinson's disease. Methods We did a meta-analysis of 17 datasets from Parkinson's disease GWAS available from European ancestry samples to nominate novel loci for disease risk. These datasets incorporated all available data. We then used these data to estimate heritable risk and develop predictive models of this heritability. We also used large gene expression and methylation resources to examine possible functional consequences as well as tissue, cell type, and biological pathway enrichments for the identified risk factors. Additionally, we examined shared genetic risk between Parkinson's disease and other phenotypes of interest via genetic correlations followed by Mendelian randomisation. Findings Between Oct 1, 2017, and Aug 9, 2018, we analysed 7·8 million single nucleotide polymorphisms in 37 688 cases, 18 618 UK Biobank proxy-cases (ie, individuals who do not have Parkinson's disease but have a first degree relative that does), and 1·4 million controls. We identified 90 independent genome-wide significant risk signals across 78 genomic regions, including 38 novel independent risk signals in 37 loci. These 90 variants explained 16–36% of the heritable risk of Parkinson's disease depending on prevalence. Integrating methylation and expression data within a Mendelian randomisation framework identified putatively associated genes at 70 risk signals underlying GWAS loci for follow-up functional studies. Tissue-specific expression enrichment analyses suggested Parkinson's disease loci were heavily brain-enriched, with specific neuronal cell types being implicated from single cell data. We found significant genetic correlations with brain volumes (false discovery rate-adjusted p=0·0035 for intracranial volume, p=0·024 for putamen volume), smoking status (p=0·024), and educational attainment (p=0·038). Mendelian randomisation between cognitive performance and Parkinson's disease risk showed a robust association (p=8·00 × 10−7). Interpretation These data provide the most comprehensive survey of genetic risk within Parkinson's disease to date, to the best of our knowledge, by revealing many additional Parkinson's disease risk loci, providing a biological context for these risk factors, and showing that a considerable genetic component of this disease remains unidentified. These associations derived from European ancestry datasets will need to be followed-up with more diverse data. Funding The National Institute on Aging at the National Institutes of Health (USA), The Michael J Fox Foundation, and The Parkinson's Foundation (see appendix for full list of funding sources)

Technical note: Assessment of blinding of hand hygiene observers in randomized controlled trials of hand hygiene interventions.

Trials evaluating interventions to improve health care workers' hand hygiene compliance use directly observed compliance as a primary outcome measure. Observers should be blinded to the intervention and the effectiveness of blinding assessed to prevent systematic bias. The literature has not addressed this issue, and this study describes a robust and pragmatic method for assessing the adequacy of blinding in hand hygiene intervention trials

Strains of Glycopeptide-Resistant Enterococcus faecium Can Alter Their van Genotypes during an Outbreak

Two isolates of Enterococcus faecium with VanA glycopeptide resistance were isolated during a hospital outbreak of E. faecium with plasmid-mediated VanB resistance. Both were found to be identical to the VanB outbreak strain by pulsed-field gel electrophoresis. The genotype of this strain changed from vanB to vanA through an intermediate isolate that contained both the vanA and vanB gene clusters on distinct plasmids