Prescribers’ perceptions of benefits and limitations of direct acting oral anticoagulants in non-valvular atrial fibrillation.

Background: There is an acknowledged lack of robust and rigorous research focusing on the perspectives of those prescribing direct acting oral anticoagulants (DOACs) for non-valvular atrial fibrillation (AF). Objective: The objective was to describe prescribers’ experiences of using DOACs in the management of non-valvular AF, including perceptions of benefits and limitations. Methods: A cross-sectional survey of prescribers in a remote and rural area of Scotland. Among other items, the questionnaire invited free-text description of positive and negative experiences of DOACs, and benefits and limitations. Responses were independently analysed by two researchers using a summative content analysis approach. This involved counting and comparison, via keywords and content, followed by interpretation and coding of the underlying context into themes. Results: One hundred and fifty-four responses were received, 120 (77.9%) from physicians, 18 (11.7%) from nurse prescribers and 10 (6.4%) from pharmacist prescribers (6 unidentified professions). Not having to monitor INR was the most cited benefit, particularly for prescribers and patients in remote and rural settings, followed by potentially improved patient adherence. These benefits were reflected in respondents’ descriptions of positive experiences and patient feedback. The main limitations were the lack of reversal agents, cost and inability to monitor anticoagulation status. Many described their experiences of adverse effects of DOACs including fatal and non-fatal bleeding, and upper gastrointestinal disturbances. Conclusions: While prescribers have positive experiences and perceive benefits of DOACs, issues such as adverse effects and inability to monitor anticoagulation status merit further monitoring and investigation. These issues are particularly relevant given the trajectory of increased prescribing of DOACs

Prescribers' views and experiences of using direct acting oral anticoagulants in the management of nonvalvular atrial fibrillation: a survey in remote and rural Scotland.

A recent systematic review highlighted the lack of robust studies on prescribers' perspectives of direct-acting oral anticoagulants (DOACs) for non-valvular atrial fibrillation (AF). The aim was to determine prescribers' views and experiences of prescribing DOACs. A cross-sectional survey of prescribers in a remote and rural area of Scotland. Survey items were: demographics; prescribing of DOACs; views of potential influences on DOAC prescribing; knowledge of prescribing guidelines; and experiences. Items on potential influences were based on the Theoretical Domains Framework (TDF). Data were analysed using descriptive and inferential statistics, and content analysis of responses to open questions. Principal component analysis (PCA) was performed on the items of potential influences. One hundred and fifty-four responses were received, 120 (77.9%) from doctors, 18 (11.7%) from nurse prescribers and 10 (6.4%) from pharmacist prescribers (6 missing). PCA of the TDF items of potential influences gave four components. Component scores for (i) role of professionals, their knowledge and skills and (ii) influences on prescribing were positive. Those for (iii) consequences of prescribing and (iv) monitoring for safety and effectiveness were more neutral. There were low levels of agreement for statements relating to DOACs being more effective, safer and cost-effective than warfarin. There were similar responses around the complexity of bleeding management and detection of over and under-anticoagulation. This study has identified several key issues of DOAC prescribing (e.g. bleeding management) hence further emphasis is required in continuing professional development and during guideline implementation and evaluation

Healthcare professional and patient views, behaviours and experiences surrounding novel oral anticoagulants (NOACs) for the management of non-valvular atrial fibrillation (AF): a systematic review protocol.

While there is a wealth of evidence on aspects such as efficacy, effectiveness, cost-effectiveness and safety, there is less evidence on the use of NOACs in clinical practice. A scoping search of MEDLINE for the years 2007-2015 has identified a number of relevant primary research. However, to date, no systematic reviews of health professional or patient views, behaviours and experiences have been published. Furthermore, a search of the Cochrane Collaboration, the Centre for Reviews and Dissemination and the Joanna Briggs Institute did not identify any registered systematic review protocols focusing on these aspects. To achieve optimal benefit and outcomes comparable to those observed in clinical trials, it is essential that NOACs are used appropriately by health professionals and patients. The evidence generated through systematic review will provide a robust and rigorous evidence base around appropriate use and hence best possible patient outcomes

Conservation of the structural and functional architecture of encapsulated ferritins in bacteria and archaea

Ferritins are a large family of intracellular proteins that protect the cell from oxidative stress by catalytically converting Fe(II) into less toxic Fe(III) and storing iron minerals within their core. Encapsulated ferritins (EncFtn) are a sub-family of ferritin-like proteins, which are widely distributed in all bacterial and archaeal phyla. The recently characterized Rhodospirillum rubrum EncFtn displays an unusual structure when compared with classical ferritins, with an open decameric structure that is enzymatically active, but unable to store iron. This EncFtn must be associated with an encapsulin nanocage in order to act as an iron store. Given the wide distribution of the EncFtn family in organisms with diverse environmental niches, a question arises as to whether this unusual structure is conserved across the family. Here, we characterize EncFtn proteins from the halophile Haliangium ochraceum and the thermophile Pyrococcus furiosus, which show the conserved annular pentamer of dimers topology. Key structural differences are apparent between the homologues, particularly in the centre of the ring and the secondary metal-binding site, which is not conserved across the homologues. Solution and native mass spectrometry analyses highlight that the stability of the protein quaternary structure differs between EncFtn proteins from different species. The ferroxidase activity of EncFtn proteins was confirmed, and we show that while the quaternary structure around the ferroxidase centre is distinct from classical ferritins, the ferroxidase activity is still inhibited by Zn(II). Our results highlight the common structural organization and activity of EncFtn proteins, despite diverse host environments and contexts within encapsulins

Supporting shared decision-making and people’s understanding of medicines : An exploration of the acceptability and comprehensibility of patient information

ACKNOWLEDGEMENTS The research team would like to thank the community pharmacy management and staff for all their assistance in facilitating recruitment. Thanks also to our colleague Alyson Brown, Robert Gordon University, for her help with recruitment and to Linda Collins, Healthcare Improvement Scotland, for assisting with project materials. We are incredibly grateful to all participants who gave up their time to participate in the research and who provided such valuable feedback.Peer reviewedPublisher PD

Large-Scale Screening of a Targeted Enterococcus faecalis Mutant Library Identifies Envelope Fitness Factors

Spread of antibiotic resistance among bacteria responsible for nosocomial and community-acquired infections urges for novel therapeutic or prophylactic targets and for innovative pathogen-specific antibacterial compounds. Major challenges are posed by opportunistic pathogens belonging to the low GC% Gram-positive bacteria. Among those, Enterococcus faecalis is a leading cause of hospital-acquired infections associated with life-threatening issues and increased hospital costs. To better understand the molecular properties of enterococci that may be required for virulence, and that may explain the emergence of these bacteria in nosocomial infections, we performed the first large-scale functional analysis of E. faecalis V583, the first vancomycin-resistant isolate from a human bloodstream infection. E. faecalis V583 is within the high-risk clonal complex 2 group, which comprises mostly isolates derived from hospital infections worldwide. We conducted broad-range screenings of candidate genes likely involved in host adaptation (e.g., colonization and/or virulence). For this purpose, a library was constructed of targeted insertion mutations in 177 genes encoding putative surface or stress-response factors. Individual mutants were subsequently tested for their i) resistance to oxidative stress, ii) antibiotic resistance, iii) resistance to opsonophagocytosis, iv) adherence to the human colon carcinoma Caco-2 epithelial cells and v) virulence in a surrogate insect model. Our results identified a number of factors that are involved in the interaction between enterococci and their host environments. Their predicted functions highlight the importance of cell envelope glycopolymers in E. faecalis host adaptation. This study provides a valuable genetic database for understanding the steps leading E. faecalis to opportunistic virulence

Socializing One Health: an innovative strategy to investigate social and behavioral risks of emerging viral threats

In an effort to strengthen global capacity to prevent, detect, and control infectious diseases in animals and people, the United States Agency for International Development’s (USAID) Emerging Pandemic Threats (EPT) PREDICT project funded development of regional, national, and local One Health capacities for early disease detection, rapid response, disease control, and risk reduction. From the outset, the EPT approach was inclusive of social science research methods designed to understand the contexts and behaviors of communities living and working at human-animal-environment interfaces considered high-risk for virus emergence. Using qualitative and quantitative approaches, PREDICT behavioral research aimed to identify and assess a range of socio-cultural behaviors that could be influential in zoonotic disease emergence, amplification, and transmission. This broad approach to behavioral risk characterization enabled us to identify and characterize human activities that could be linked to the transmission dynamics of new and emerging viruses. This paper provides a discussion of implementation of a social science approach within a zoonotic surveillance framework. We conducted in-depth ethnographic interviews and focus groups to better understand the individual- and community-level knowledge, attitudes, and practices that potentially put participants at risk for zoonotic disease transmission from the animals they live and work with, across 6 interface domains. When we asked highly-exposed individuals (ie. bushmeat hunters, wildlife or guano farmers) about the risk they perceived in their occupational activities, most did not perceive it to be risky, whether because it was normalized by years (or generations) of doing such an activity, or due to lack of information about potential risks. Integrating the social sciences allows investigations of the specific human activities that are hypothesized to drive disease emergence, amplification, and transmission, in order to better substantiate behavioral disease drivers, along with the social dimensions of infection and transmission dynamics. Understanding these dynamics is critical to achieving health security--the protection from threats to health-- which requires investments in both collective and individual health security. Involving behavioral sciences into zoonotic disease surveillance allowed us to push toward fuller community integration and engagement and toward dialogue and implementation of recommendations for disease prevention and improved health security

Searching for stochastic gravitational waves using data from the two colocated LIGO Hanford detectors

Searches for a stochastic gravitational-wave background (SGWB) using terrestrial detectors typically involve cross-correlating data from pairs of detectors. The sensitivity of such cross-correlation analyses depends, among other things, on the separation between the two detectors: the smaller the separation, the better the sensitivity. Hence, a colocated detector pair is more sensitive to a gravitational-wave background than a noncolocated detector pair. However, colocated detectors are also expected to suffer from correlated noise from instrumental and environmental effects that could contaminate the measurement of the background. Hence, methods to identify and mitigate the effects of correlated noise are necessary to achieve the potential increase in sensitivity of colocated detectors. Here we report on the first SGWB analysis using the two LIGO Hanford detectors and address the complications arising from correlated environmental noise. We apply correlated noise identification and mitigation techniques to data taken by the two LIGO Hanford detectors, H1 and H2, during LIGO’s fifth science run. At low frequencies, 40–460 Hz, we are unable to sufficiently mitigate the correlated noise to a level where we may confidently measure or bound the stochastic gravitational-wave signal. However, at high frequencies, 460–1000 Hz, these techniques are sufficient to set a 95% confidence level upper limit on the gravitational-wave energy density of Ω(f) < 7.7 × 10[superscript -4](f/900  Hz)[superscript 3], which improves on the previous upper limit by a factor of ~180. In doing so, we demonstrate techniques that will be useful for future searches using advanced detectors, where correlated noise (e.g., from global magnetic fields) may affect even widely separated detectors.National Science Foundation (U.S.)United States. National Aeronautics and Space AdministrationCarnegie TrustDavid & Lucile Packard FoundationAlfred P. Sloan Foundatio

Search for gravitational-lensing signatures in the full third observing run of the LIGO-Virgo network

Gravitational lensing by massive objects along the line of sight to the source causes distortions of gravitational wave-signals; such distortions may reveal information about fundamental physics, cosmology and astrophysics. In this work, we have extended the search for lensing signatures to all binary black hole events from the third observing run of the LIGO--Virgo network. We search for repeated signals from strong lensing by 1) performing targeted searches for subthreshold signals, 2) calculating the degree of overlap amongst the intrinsic parameters and sky location of pairs of signals, 3) comparing the similarities of the spectrograms amongst pairs of signals, and 4) performing dual-signal Bayesian analysis that takes into account selection effects and astrophysical knowledge. We also search for distortions to the gravitational waveform caused by 1) frequency-independent phase shifts in strongly lensed images, and 2) frequency-dependent modulation of the amplitude and phase due to point masses. None of these searches yields significant evidence for lensing. Finally, we use the non-detection of gravitational-wave lensing to constrain the lensing rate based on the latest merger-rate estimates and the fraction of dark matter composed of compact objects