902 research outputs found

    Biosimilar infliximab introduction into the gastro-enterology care pathway in a large acute Irish teaching hospital: a story behind the evidence

    Get PDF
    Background and aim: Biosimilar medicines are not considered exact replicas of originator biological medicines. As a result, prescribers can be hesitant to introduce such medicines into the clinical setting until evidence surfaces confirming their safety and effectiveness. In Ireland, a national biosimilar medicines policy is currently in development but the decision to prescribe biosimilar medicines remains at the discretion of the physician. The aim of this descriptive review is to tell the story of the evidence used by a large acute Irish teaching hospital to introduce biosimilar infliximab CT-P13 for the treatment of inflammatory bowel disease (IBD) in a safe and timely manner into routine care. Methods: To explore the evidence supporting the effective introduction of biosimilar infliximab in a large acute Irish teaching hospital, a literature review was conducted. Evidence consisted of published studies, reviews, reports, position statements, articles, clinical guidelines, and recommendations from national bodies, regulatory authorities and professional organizations. All evidence was published in English. Results and discussion: In September 2014, the accumulated evidence base provided physicians with reassurance to prescribe biosimilar infliximab CT-P13 for new patients suffering from IBD in this large acute Irish teaching hospital. In September 2016, as the evidence base grew, physicians began to safely and confidently switch patients from the originator infliximab product to the biosimilar product. Conclusion: There was a significant time lag between regulatory approval and clinical acceptance given that the European Medicines Agency had granted market authorization for biosimilar infliximab CT-P13 three years prior to the initiation of this hospital's switching process. Although conservative in their execution, the authors conclude that with the existential concern and uncertainty still surrounding biosimilar medicines, a distinct and individualized approach for biosimilar medicine implementation is required. It is with hope that the Irish biosimilar medicines policy will improve upon biosimilar medicine clinical acceptance once published

    Controlled Release of Multiple Therapeutics From Silicone Hydrogel Contact Lenses for Post-Cataract/Post-Refractive Surgery and Uveitis Treatment.

    Get PDF
    PURPOSE: This work demonstrates seven-day controlled and extended in vitro physiological flow dual release of multiple post-ocular surgery therapeutics from extended-wear contact lenses as a dropless alternative for treatment of uveitis and corneal inflammation, pain, and infection. Lens replacement each week optimizes treatment matching patient recall time with the ability to increase or decrease dosage. METHODS: Lenses were synthesized using molecular imprinting to create lenses with macromolecular memory for diclofenac sodium (DS) and dexamethasone sodium phosphate (DMSP), as well as bromfenac sodium (BS) and moxifloxacin (MOX). Drug uptake and release were analyzed, and physical properties were measured and compared to commercial standards. RESULTS: DS + DMSP-loaded lenses demonstrated seven-days-plus release of each, whereas controls released more than 85% of their payload within the first day. Lenses loaded with BS + MOX demonstrated release of BS and MOX for 11 and eight days, respectively. Structural analysis demonstrated statistically similar mesh size and average molecular weight between crosslinks between imprinted lenses and controls, suggesting that release extension was due to formation of macromolecular memory sites rather than a tighter polymer architecture. CONCLUSIONS: Lenses demonstrated in this work have significant clinical applications as an eye drop alternative, possessing the ability to be worn continuously for one week while delivering a consistent amount of therapeutic for the duration of wear. TRANSLATIONAL RELEVANCE: In vitro physiological flow release results demonstrate the clinical potential of therapeutic contact lenses as a dropless vehicle for ocular drug delivery

    Quantitative trait loci associated with different polar metabolites in perennial ryegrass - providing scope for breeding towards increasing certain polar metabolites

    Get PDF
    peer-reviewedBackground Recent advances in the mapping of biochemical traits have been reported in Lolium perenne. Although the mapped traits, including individual sugars and fatty acids, contribute greatly towards ruminant productivity, organic acids and amino acids have been largely understudied despite their influence on the ruminal microbiome. Results In this study, we used a targeted gas-chromatography mass spectrometry (GC-MS) approach to profile the levels of 25 polar metabolites from different classes (sugars, amino acids, phenolic acids, organic acids and other nitrogen-containing compounds) present in a L. perenne F2 population consisting of 325 individuals. A quantitative trait (QTL) mapping approach was applied and successfully identified QTLs regulating seven of those polar metabolites (L-serine, L-leucine, glucose, fructose, myo-inositol, citric acid and 2, 3-hydroxypropanoic acid).Two QTL mapping approaches were carried out using SNP markers on about half of the population only and an imputation approach using SNP and DArT markers on the entire population. The imputation approach confirmed the four QTLs found in the SNP-only analysis and identified a further seven QTLs. Conclusions These results highlight the potential of utilising molecular assisted breeding in perennial ryegrass to modulate a range of biochemical quality traits with downstream effects in livestock productivity and ruminal digestion.This study was financed through a Research Stimulus Fund Grant by the Irish Department of Agriculture, Fisheries and Marine (RSF 06–346). AF, CH and DS acknowledge support from The Scottish Government’s Rural and Environment Science and Analytical Services Division

    Transcriptome sequencing of Festulolium accessions under salt stress

    Get PDF
    peer-reviewedObjectives The objective of this study was to establish transcriptome assemblies of Festulolium hybrids under salt stress, and identify genes regulated across the hybrids in response to salt stress. The development of transcriptome assemblies for Festulolium hybrids and cataloguing of genes regulated under salt stress will facilitate further downstream studies. Results Plants were grown at three salt concentrations (0.5%, 1% and 1.5%) and phenotypic and transcriptomic data was collected. Salt stress was confirmed by progressive loss of green leaves as salt concentration increased from 0 to 1.5%. We generated de-novo transcriptome assemblies for two Festulolium pabulare festucoid genotypes, for a single Festulolium braunii genotype, and a single F. pabulare loloid genotype. We also identified 1555 transcripts that were up regulated and 1264 transcripts that were down regulated in response to salt stress in the Festulolium hybrids. Some of the identified transcripts showed significant sequence similarity with genes known to be regulated during salt and other abiotic stresses

    Computerised interventions designed to reduce potentially inappropriate prescribing in hospitalised older adults: a systematic review and meta-analysis

    Get PDF
    Background: computerised interventions have been suggested as an effective strategy to reduce potentially inappropriate prescribing (PIP) for hospitalised older adults. This systematic review and meta-analysis examined the evidence for efficacy of computerised interventions designed to reduce PIP in this patient group. Methods: an electronic literature search was conducted using eight databases up to October 2017. Included studies were controlled trials of computerised interventions aiming to reduce PIP in hospitalised older adults (≥65 years). Risk of bias was assessed using Cochrane’s Effective Practice and Organisation of Care criteria. Results: of 653 records identified, eight studies were included—two randomised controlled trials, two interrupted time series analysis studies and four controlled before–after studies. Included studies were mostly at a low risk of bias. Overall, seven studies showed either a statistically significant reduction in the proportion of patients prescribed a potentially inappropriate medicine (PIM) (absolute risk reduction {ARR} 1.3–30.1%), or in PIMs ordered (ARR 2–5.9%). However, there is insufficient evidence thus far to suggest that these interventions can routinely improve patient-related outcomes. It was only possible to include three studies in the meta-analysis—which demonstrated that intervention patients were less likely to be prescribed a PIM (odds ratio 0.6; 95% CI 0.38, 0.93). No computerised intervention targeting potential prescribing omissions (PPOs) was identified. Conclusions: this systematic review concludes that computerised interventions are capable of statistically significantly reducing PIMs in hospitalised older adults. Future interventions should strive to target both PIMs and PPOs, ideally demonstrating both cost-effectiveness data and clinically significant improvements in patient-related outcomes

    Genomic prediction of crown rust resistance in Lolium perenne

    Get PDF
    peer-reviewedBackground Genomic selection (GS) can accelerate genetic gains in breeding programmes by reducing the time it takes to complete a cycle of selection. Puccinia coronata f. sp lolli (crown rust) is one of the most widespread diseases of perennial ryegrass and can lead to reductions in yield, persistency and nutritional value. Here, we used a large perennial ryegrass population to assess the accuracy of using genome wide markers to predict crown rust resistance and to investigate the factors affecting predictive ability. Results Using these data, predictive ability for crown rust resistance in the complete population reached a maximum of 0.52. Much of the predictive ability resulted from the ability of markers to capture genetic relationships among families within the training set, and reducing the marker density had little impact on predictive ability. Using permutation based variable importance measure and genome wide association studies (GWAS) to identify and rank markers enabled the identification of a small subset of SNPs that could achieve predictive abilities close to those achieved using the complete marker set. Conclusion Using a GWAS to identify and rank markers enabled a small panel of markers to be identified that could achieve higher predictive ability than the same number of randomly selected markers, and predictive abilities close to those achieved with the entire marker set. This was particularly evident in a sub-population characterised by having on-average higher genome-wide linkage disequilibirum (LD). Higher predictive abilities with selected markers over random markers suggests they are in LD with QTL. Accuracy due to genetic relationships will decay rapidly over generations whereas accuracy due to LD will persist, which is advantageous for practical breeding applications.This work received funding from the Irish Department of Agriculture Food and the Marine DAFM (RSF 11/S/109) and Teagasc core funding. SKA is supported by a Teagasc PhD Walsh Fellowship. SLB has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No. 658031

    Human Performance Models of Pilot Behavior

    Get PDF
    Five modeling teams from industry and academia were chosen by the NASA Aviation Safety and Security Program to develop human performance models (HPM) of pilots performing taxi operations and runway instrument approaches with and without advanced displays. One representative from each team will serve as a panelist to discuss their team s model architecture, augmentations and advancements to HPMs, and aviation-safety related lessons learned. Panelists will discuss how modeling results are influenced by a model s architecture and structure, the role of the external environment, specific modeling advances and future directions and challenges for human performance modeling in aviation
    • …
    corecore