Fragmentation of care threatens patient safety in peripheral vascular catheter management in acute care--a qualitative study.

BACKGROUND: The use of peripheral vascular catheters (PVCs) is an extremely common and necessary clinical intervention, but inappropriate PVC care poses a major patient safety risk in terms of infection. Quality improvement initiatives have been proposed to reduce the likelihood of adverse events, but a lack of understanding about factors that influence behaviours of healthcare professionals limits the efficacy of such interventions. We undertook qualitative interviews with clinical staff from a large group of hospitals in order to understand influences on PVC care behaviors and subsequent patient safety. METHODS: Ten doctors, ten clinical pharmacists, 18 nurses and one midwife at a National Health Service hospital group in London (United Kingdom) were interviewed between December 2010 and July 2011 using qualitative methods. Responses were analysed using a thematic framework. RESULTS: FOUR KEY THEMES EMERGED: 1) Fragmentation of management and care, demonstrated with a lack of general overview and insufficient knowledge about expected standards of care or responsibility of different professionals; 2) feelings of resentment and frustration as a result of tensions in the workplace, due to the ambiguity about professional responsibilities; 3) disregard for existing hospital policy due to perceptions of flaws in the evidence used to support it; and 4) low-risk perception for the impact of PVC use on patient safety. CONCLUSION: Fragmentation of practice resulted in ill-defined responsibilities and interdisciplinary resentment, which coupled with a generally low perception of risk of catheter use, appeared to result in lack of maintaining policy PVC standards which could reduced patient safety. Resolution of these issues through clearly defining handover practice, teaching interdisciplinary duties and increasing awareness of PVC risks could result in preventing thousands of BSIs and other PVC-related infections annually

Designing high-quality implementation research: development, application, feasibility and preliminary evaluation of the implementation science research development (ImpRes) tool and guide

Background:  Designing implementation research can be a complex and daunting task, especially for applied health researchers who have not received specialist training in implementation science. We developed the Implementation Science Research Development (ImpRes) tool and supplementary guide to address this challenge and provide researchers with a systematic approach to designing implementation research. Methods:  A multi-method and multi-stage approach was employed. An international, multidisciplinary expert panel engaged in an iterative brainstorming and consensus-building process to generate core domains of the ImpRes tool, representing core implementation science principles and concepts that researchers should consider when designing implementation research. Simultaneously, an iterative process of reviewing the literature and expert input informed the development and content of the tool. Once consensus had been reached, specialist expert input was sought on involving and engaging patients/service users; and economic evaluation. ImpRes was then applied to 15 implementation and improvement science projects across the National Institute of Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care (CLAHRC) South London, a research organisation in London, UK. Researchers who applied the ImpRes tool completed an 11-item questionnaire evaluating its structure, content and usefulness. Results:  Consensus was reached on ten implementation science domains to be considered when designing implementation research. These include implementation theories, frameworks and models, determinants of implementation, implementation strategies, implementation outcomes and unintended consequences. Researchers who used the ImpRes tool found it useful for identifying project areas where implementation science is lacking (median 5/5, IQR 4–5) and for improving the quality of implementation research (median 4/5, IQR 4–5) and agreed that it contained the key components that should be considered when designing implementation research (median 4/5, IQR 4–4). Qualitative feedback from researchers who applied the ImpRes tool indicated that a supplementary guide was needed to facilitate use of the tool. Conclusions:  We have developed a feasible and acceptable tool, and supplementary guide, to facilitate consideration and incorporation of core principles and concepts of implementation science in applied health implementation research. Future research is needed to establish whether application of the tool and guide has an effect on the quality of implementation research

A multi-centre quality improvement project to reduce the incidence of obstetric anal sphincter injury (OASI): study protocol.

BACKGROUND: Third and fourth degree perineal tears, or obstetric anal sphincter injuries (OASI), sustained during childbirth can result in anal incontinence and psychosocial problems which require ongoing treatment. Within the English National Health System (NHS) reported rates of OASI have gradually increased. In response, a care bundle was developed incorporating four elements: 1) antenatal information to women, 2) manual perineal protection during all vaginal births, 3) episiotomy to be performed with a 60° mediolateral angle at crowning (when clinically indicated) and 4) perineal examination (including per rectum) after childbirth. Implementation of the OASI Care Bundle is aided by a skills development module and an awareness campaign. The project is a collaboration between two national professional bodies, an NHS hospital trust and an academic institution. METHODS: Implementation of the OASI Care Bundle will be evaluated using a stepped-wedge design. From January 2017 sixteen maternity units across England, Wales and Scotland will participate in the study over a 15-month period, with sequential roll-out of the intervention in four blocks (regions) of four units. The primary clinical outcome is OASI rate. Regression analysis will adjust for differences in organisational characteristics and obstetric risk factors in women who gave birth before and after implementation of the care bundle. Focus group discussions and in-depth interviews with clinicians will evaluate the feasibility of integrating the care bundle into routine practice. Interviews with women will explore the acceptability of the intervention. DISCUSSION: This protocol outlines the evaluation of our quality improvement project which aims to prevent OASI using a bundle of evidence-based interventions that are each widely used in practice. The OASI project aims to 1) standardise practice to prevent OASI in a way that is acceptable to clinicians and women and 2) identify the barriers and enablers associated with upscaling interventions within maternity units. If found to be effective, feasible and acceptable, the OASI Care Bundle will be shared with a range of audiences using the communication channels available to the professional bodies. TRIAL REGISTRATION: The OASI Project was retrospectively registered on the ISCTRN12143325 database date assigned 03/10/2017

Lessons for fisheries management from the EU cod recovery plan

The performance of the EU long-term management plan for cod stocks, in force since 2009, is analysed focusing on the human and institutional factors. The plan operates through landings quotas (TACs) and effort restrictions following a Harvest Control Rule, and deploys a novel instrument allowing Member States to ‘buy back’ or increase fishing effort for fleet segments engaged in cod-avoidance measures. The stipulated fishing mortality reductions have not been achieved. On the positive side, the ‘buy-back’ instrument has led to increased uptake of selective gear and implementation of permanent and real- time temporary closures. On the negative side, ignoring the dimension of fishers as reactive agents in the design, the impact assessment, and the annual implementation of the measures has contributed to the failure to adequately implement the plan and achieve its objectives.JRC.G.4-Maritime affair

Genetics of circulating inflammatory proteins identifies drivers of immune-mediated disease risk and therapeutic targets

Circulating proteins have important functions in inflammation and a broad range of diseases. To identify genetic influences on inflammation-related proteins, we conducted a genome-wide protein quantitative trait locus (pQTL) study of 91 plasma proteins measured using the Olink Target platform in 14,824 participants. We identified 180 pQTLs (59 cis, 121 trans). Integration of pQTL data with eQTL and disease genome-wide association studies provided insight into pathogenesis, implicating lymphotoxin-alpha in multiple sclerosis. Using Mendelian randomization (MR) to assess causality in disease etiology, we identified both shared and distinct effects of specific proteins across immune-mediated diseases, including directionally discordant effects of CD40 on risk of rheumatoid arthritis versus multiple sclerosis and inflammatory bowel disease. MR implicated CXCL5 in the etiology of ulcerative colitis (UC) and we show elevated gut CXCL5 transcript expression in patients with UC. These results identify targets of existing drugs and provide a powerful resource to facilitate future drug target prioritization. Here the authors identify genetic effectors of the level of inflammation-related plasma proteins and use Mendelian randomization to identify proteins that contribute to immune-mediated disease risk

In Vivo Imaging of Tau Pathology Using Magnetic Resonance Imaging Textural Analysis

BACKGROUND: Non-invasive characterization of the pathological features of Alzheimer's disease (AD) could enhance patient management and the development of therapeutic strategies. Magnetic resonance imaging texture analysis (MRTA) has been used previously to extract texture descriptors from structural clinical scans in AD to determine cerebral tissue heterogeneity. In this study, we examined the potential of MRTA to specifically identify tau pathology in an AD mouse model and compared the MRTA metrics to histological measures of tau burden. METHODS: MRTA was applied to T2 weighted high-resolution MR images of nine 8.5-month-old rTg4510 tau pathology (TG) mice and 16 litter matched wild-type (WT) mice. MRTA comprised of the filtration-histogram technique, where the filtration step extracted and enhanced features of different sizes (fine, medium, and coarse texture scales), followed by quantification of texture using histogram analysis (mean gray level intensity, mean intensity, entropy, uniformity, skewness, standard-deviation, and kurtosis). MRTA was applied to manually segmented regions of interest (ROI) drawn within the cortex, hippocampus, and thalamus regions and the level of tau burden was assessed in equivalent regions using histology. RESULTS: Texture parameters were markedly different between WT and TG in the cortex (E, p < 0.01, K, p < 0.01), the hippocampus (K, p < 0.05) and in the thalamus (K, p < 0.01). In addition, we observed significant correlations between histological measurements of tau burden and kurtosis in the cortex, hippocampus and thalamus. CONCLUSIONS: MRTA successfully differentiated WT and TG in brain regions with varying degrees of tau pathology (cortex, hippocampus, and thalamus) based on T2 weighted MR images. Furthermore, the kurtosis measurement correlated with histological measures of tau burden. This initial study indicates that MRTA may have a role in the early diagnosis of AD and the assessment of tau pathology using routinely acquired structural MR images

Relative Roles of the Cellular and Humoral Responses in the Drosophila Host Defense against Three Gram-Positive Bacterial Infections

BACKGROUND: Two NF-kappaB signaling pathways, Toll and immune deficiency (imd), are required for survival to bacterial infections in Drosophila. In response to septic injury, these pathways mediate rapid transcriptional activation of distinct sets of effector molecules, including antimicrobial peptides, which are important components of a humoral defense response. However, it is less clear to what extent macrophage-like hemocytes contribute to host defense. METHODOLOGY/PRINCIPAL FINDINGS: In order to dissect the relative importance of humoral and cellular defenses after septic injury with three different gram-positive bacteria (Micrococcus luteus, Enterococcus faecalis, Staphylococcus aureus), we used latex bead pre-injection to ablate macrophage function in flies wildtype or mutant for various Toll and imd pathway components. We found that in all three infection models a compromised phagocytic system impaired fly survival--independently of concomitant Toll or imd pathway activation. Our data failed to confirm a role of the PGRP-SA and GNBP1 Pattern Recognition Receptors for phagocytosis of S. aureus. The Drosophila scavenger receptor Eater mediates the phagocytosis by hemocytes or S2 cells of E. faecalis and S. aureus, but not of M. luteus. In the case of M. luteus and E. faecalis, but not S. aureus, decreased survival due to defective phagocytosis could be compensated for by genetically enhancing the humoral immune response. CONCLUSIONS/SIGNIFICANCE: Our results underscore the fundamental importance of both cellular and humoral mechanisms in Drosophila immunity and shed light on the balance between these two arms of host defense depending on the invading pathogen

From insect to man: Photorhabdus sheds light on the emergence of human pathogenicity

Photorhabdus are highly effective insect pathogenic bacteria that exist in a mutualistic relationship with Heterorhabditid nematodes. Unlike other members of the genus, Photorhabdus asymbiotica can also infect humans. Most Photorhabdus cannot replicate above 34°C, limiting their host-range to poikilothermic invertebrates. In contrast, P. asymbiotica must necessarily be able to replicate at 37°C or above. Many well-studied mammalian pathogens use the elevated temperature of their host as a signal to regulate the necessary changes in gene expression required for infection. Here we use RNA-seq, proteomics and phenotype microarrays to examine temperature dependent differences in transcription, translation and phenotype of P. asymbiotica at 28°C versus 37°C, relevant to the insect or human hosts respectively. Our findings reveal relatively few temperature dependant differences in gene expression. There is however a striking difference in metabolism at 37°C, with a significant reduction in the range of carbon and nitrogen sources that otherwise support respiration at 28°C. We propose that the key adaptation that enables P. asymbiotica to infect humans is to aggressively acquire amino acids, peptides and other nutrients from the human host, employing a so called “nutritional virulence” strategy. This would simultaneously cripple the host immune response while providing nutrients sufficient for reproduction. This might explain the severity of ulcerated lesions observed in clinical cases of Photorhabdosis. Furthermore, while P. asymbiotica can invade mammalian cells they must also resist immediate killing by humoral immunity components in serum. We observed an increase in the production of the insect Phenol-oxidase inhibitor Rhabduscin normally deployed to inhibit the melanisation immune cascade. Crucially we demonstrated this molecule also facilitates protection against killing by the alternative human complement pathway