Uptake of oral anticoagulants for stroke prevention in patients with atrial fibrillation in a single Clinical Commissioning Group in England without restrictions to their use

YesBackground and Objective In England, the uptake of direct oral anticoagulants (DOACs) for stroke prevention in atrial fbrillation has been slow and varied across diferent Clinical Commissioning Groups (CCGs). This study aimed to profle the prescribing of oral anticoagulants for stroke prevention in patients with atrial fbrillation over 3 years in a CCG without restrictions to DOACs use to understand more about organisational and/or individual barriers to the early uptake of DOACs. Methods Data were collected from nine general practices between 1 April 2012 and 31 March 2015 of patients who were initiated on the oral anticoagulant therapy. Data were analysed descriptively and with independent Student’s t test and Chi square test to explore if there was an association between type of oral anticoagulant initiated and sex, age, type of prescriber and prior aspirin use. Results The early uptake of DOACs signifcantly increased over the study period (p<0.0001; medium size efect φc=0.372). There was no statistically signifcant diference between sex or age and type of oral anticoagulant initiated. Primary-care prescribers were responsible for initiating the majority of oral anticoagulants (71%; N=257) and driving the use of DOACs (72%, N=71). Patients switched from aspirin to an oral anticoagulant were more likely to be initiated on warfarin than a DOAC. Conclusions The early use of DOACs, in a CCG without restrictions to their use, was embraced by primary-care prescribers in this particular CCG.Bayer Pharmaceuticals via an unrestricted educational grant

Oral anticoagulants for stroke prevention in nonvalvular AF

yesWarfarin and direct oral anticoagulants (DOACs) have been shown to reduce the risk of stroke in patients with atrial fibrillation, yet many patients are still not being anticoagulated. This article discusses the barriers to the initiation of oral anticoagulants, in particular DOACs, and how these can be overcome

How effective are primary care pharmacists at running dyspepsia clinics for patients prescribed PPIs?

YesIntroduction As a consequence of the low cost and perceived safety, proton pump inhibitors (PPIs) are widely prescribed but they can cause longterm adverse effects and are often overprescribed. For most patients PPIs should not be continued long-term as patients can become dependent on PPIs and they are rarely stepped down/off treatment. We aimed to measure whether a dyspepsia review service could help patients on PPIs to step down/off treatment whilst still keeping them symptom free. Methods Pharmacists were provided with training on dyspepsia management. Four general practices were selected. Patients taking a PPI for more than two months were included. A list of exclusion criteria (e.g. active ulcers, newly initiated) was applied. Between six and eight dyspepsia review clinics were run at each site. Patients were booked into a 15-minute consultation. A concordance style consultation was held with clinicians providing information on dyspepsia management and exploring the patients’ ideas, concerns and expectations about stepping down or stepping off treatment. A follow-up audit was performed at four months to determine if patients had remained stepped down/off. An economic evaluation of clinic costs and drugs savings was performed. Results A total of 508 patients were invited to a review; 136 did not attend and 58 were excluded due to not meeting the inclusion criteria, leaving 314 patients reviewed for step-down/step-off. Successful step down/step off was achieved in 257 people (82% of those reviewed). The total cost savings of PPIs was £7,100. The additional cost of alginates was £1,207 giving a net saving on medicines of £5,893 per annum. Set-up costs were £1,194 and staff costs £3,524 to £5,156 giving total running costs, which vary dependent on the Agenda for Change (AfC) grade of pharmacist involved, of £4,720 - £6,351. Conclusion A dyspepsia review clinic is cost-neutral to run but, given that many patients are on polypharmacy, PPI step down might best be considered as part of a holistic medication review clinic.Reckitt Benckiser, National Institute for Health Research, Health Education Englan

Evaluating recruitment methods of patients with advanced cancer: a pragmatic opportunistic comparison

YesBackground: Recruitment of patients with advanced cancer into studies is challenging. Objective: To evaluate recruitment methods in a study of pharmacist-led cancer pain medicines consultations and produce recommendations for future studies. Method: Two methods of recruitment were employed: 1) community-based (general practitioner computer search, identification by general practitioner, community pharmacist or district nurse and hospital outpatient list search), and 2) hospice-based (in and outpatient list search). Patients identified in method 1 were invited by post and in method 2 were invited face-to-face. Information was designed in collaboration with patients and carers. Results: 128 patients were identified (85 from the community and 43 from the hospice), 47 met the inclusion criteria. Twenty-three agreed to take part and 19 completed the study, 17 of whom were already under specialist palliative care. Recruitment rates were 7% for community-based methods and 40% for hospice. The recruitment methods differed in intensity of resource use. Recruitment via letter and a lack of engagement by healthcare professionals were found to be barriers. Facilitators included the researcher having personal involvement in recruitment. Conclusion: The overall recruitment rate was in line with other studies for this patient cohort. Attempts to identify and engage patients through community-based postal contact were less effective than where personal contact with patients was both possible and occurred. Methods were less successful at recruiting patients who were not already engaged with hospice services.Programme Grants for Applied Research. Grant Number: RP-PG-0610-1011

A New Population of High-z, Dusty Lyα Emitters and Blobs Discovered by WISE: Feedback Caught in the Act?

By combining data from the NASA Wide-field Infrared Survey Explorer (WISE) mission with optical spectroscopy from the W. M. Keck telescope, we discover a mid-IR color criterion that yields a 78% success rate in identifying rare, typically radio-quiet, 1.6 ≾ z ≾ 4.6 dusty Lyα emitters (LAEs). Of these, at least 37% have emission extended on scales of 30-100 kpc and are considered Lyα "blobs" (LABs). The objects have a surface density of only ~0.1 deg^(–2), making them rare enough that they have been largely missed in deep, small area surveys. We measured spectroscopic redshifts for 92 of these galaxies, and find that the LAEs (LABs) have a median redshift of 2.3 (2.5). The WISE photometry coupled with data from Herschel (Herschel is an ESA space observatory with science instruments provided by European-led Principal Investigator consortia and with important participation from NASA) reveals that these galaxies are in the Hyper Luminous IR galaxy regime (L IR ≳ 10^(13)-10^(14) L_☉) and have warm colors. They are typically more luminous and warmer than other dusty, z ~ 2 populations such as submillimeter-selected galaxies and dust-obscured galaxies. These traits are commonly associated with the dust being illuminated by intense active galactic nucleus activity. We hypothesize that the combination of spatially extended Lyα, large amounts of warm IR-luminous dust, and rarity (implying a short-lived phase) can be explained if the galaxies are undergoing brief, intense "feedback" transforming them from an extreme dusty starburst/QSO into a mature galaxy

Patient Perspectives on Factors Affecting Direct Oral Anticoagulant Use for Stroke Prevention in Atrial Fibrillation

YesIntroduction: Oral anticoagulant therapy choices for patients with atrial fibrillation (AF) expanded in the last decade with the introduction of direct oral anticoagulants (DOAC). However, the implementation of DOACs was slow and varied across different health economies in England. There is limited evidence on the patient role in the uptake of new medicines, including DOACs, apart from considering their demographic and clinical characteristics. Hence, this study aimed to address the gap by exploring the view of patients with AF on factors affecting DOAC use. Methods: A qualitative study using semi-structured interviews was conducted in three health economies in the North of England. Adult patients (>18 years) diagnosed with non-valvular AF, prescribed an oral anticoagulant (vitamin K antagonist or DOAC), and able to give written consent were recruited. Data were collected between August 2018 and April 2019. Audio recorded interviews were transcribed verbatim and analyzed using the framework method. Results: Four themes with eleven subthemes discussed identified factors affecting the use of DOACs. They were linked to limited healthcare financial and workforce resources, patient involvement in decision-making, patient knowledge about DOACs, safety concerns about oral anticoagulants, and oral anticoagulant therapy impact on patients' daily lives. Lack of a) opportunities to voice patient preferences and b) information on available therapy options resulted in some patients experiencing difficulties with the prescribed therapy. This was reported to cause negative impact on their daily lives, adherence, and overall satisfaction with the therapy. Conclusion: Greater patient involvement in decision-making could prevent and resolve difficulties encountered by some patients and potentially improve outcomes plus increase the uptake of DOACs.Pharmacy Research UK (PRUK-2018-GA-1-KM) and Leeds Teaching Hospitals NHS Trus

Barriers and facilitators to the uptake of new medicines into clinical practice: a systematic review

YesImplementation and uptake of novel and cost-effective medicines can improve patient health outcomes and healthcare efficiency. However, the uptake of new medicines into practice faces a wide range of obstacles. Earlier reviews provided insights into determinants for new medicine uptake (such as medicine, prescriber, patient, organization, and external environment factors). However, the methodological approaches used had limitations (e.g., single author, narrative review, narrow search, no quality assessment of reviewed evidence). This systematic review aims to identify barriers and facilitators affecting the uptake of new medicines into clinical practice and identify areas for future research. A systematic search of literature was undertaken within seven databases: Medline, EMBASE, Web of Science, CINAHL, Cochrane Library, SCOPUS, and PsychINFO. Included in the review were qualitative, quantitative, and mixed-methods studies focused on adult participants (18 years and older) requiring or taking new medicine(s) for any condition, in the context of healthcare organizations and which identified factors affecting the uptake of new medicines. The methodological quality was assessed using QATSDD tool. A narrative synthesis of reported factors was conducted using framework analysis and a conceptual framework was utilised to group them. A total of 66 studies were included. Most studies (n = 62) were quantitative and used secondary data (n = 46) from various databases, e.g., insurance databases. The identified factors had a varied impact on the uptake of the different studied new medicines. Differently from earlier reviews, patient factors (patient education, engagement with treatment, therapy preferences), cost of new medicine, reimbursement and formulary conditions, and guidelines were suggested to influence the uptake. Also, the review highlighted that health economics, wider organizational factors, and underlying behaviours of adopters were not or under explored. This systematic review has identified a broad range of factors affecting the uptake of new medicines within healthcare organizations, which were grouped into patient, prescriber, medicine, organizational, and external environment factors. This systematic review also identifies additional factors affecting new medicine use not reported in earlier reviews, which included patient influence and education level, cost of new medicines, formulary and reimbursement restrictions, and guidelines. PROSPERO database (CRD42018108536).This work presents research funded by the Pharmacy Research UK (grant reference: PRUK-2018-GA-1-KM) and Leeds Teaching Hospitals NHS Trust

Understanding long-term opioid prescribing for non-cancer pain in primary care: A qualitative study

YesBackground: The place of opioids in the management of chronic, non-cancer pain is limited. Even so their use is escalating, leading to concerns that patients are prescribed strong opioids inappropriately and alternatives to medication are under-used. We aimed to understand the processes which bring about and perpetuate long-term prescribing of opioids for chronic, non-cancer pain. Methods: We held semi-structured interviews with patients and focus groups with general practitioners (GPs). Participants included 23 patients currently prescribed long-term opioids and 15 GPs from Leeds and Bradford, United Kingdom (UK). We used a grounded approach to the analysis of transcripts. Results: Patients are driven by the needs for pain relief, explanation, and improvement or maintenance of quality of life. GPs’ responses are shaped by how UK general practice is organised, available therapeutic choices and their expertise in managing chronic pain, especially when facing diagnostic uncertainty or when their own approach is at odds with the patient’s wishes. Four features of the resulting transaction between patients and doctors influence prescribing: lack of clarity of strategy, including the risk of any plans being subverted by urgent demands; lack of certainty about locus of control in decision-making, especially in relation to prescribing; continuity in the doctor-patient relationship; and mutuality and trust. Conclusions: Problematic prescribing occurs when patients experience repeated consultations that do not meet their needs and GPs feel unable to negotiate alternative approaches to treatment. Therapeutic short-termism is perpetuated by inconsistent clinical encounters and the absence of mutually-agreed formulations of underlying problems and plans of action. Apart from commissioning improved access to appropriate specialist services, general practices should also consider how they manage problematic opioid prescribing and be prepared to set boundaries with patients.National Institute for Health Research (NIHR) under its Research for Patient Benefit Programme (Grant Reference Number PB-PG- 1010–23041)

Evidence for a lineage of virulent bacteriophages that target Campylobacter.

BACKGROUND: Our understanding of the dynamics of genome stability versus gene flux within bacteriophage lineages is limited. Recently, there has been a renewed interest in the use of bacteriophages as 'therapeutic' agents; a prerequisite for their use in such therapies is a thorough understanding of their genetic complement, genome stability and their ecology to avoid the dissemination or mobilisation of phage or bacterial virulence and toxin genes. Campylobacter, a food-borne pathogen, is one of the organisms for which the use of bacteriophage is being considered to reduce human exposure to this organism. RESULTS: Sequencing and genome analysis was performed for two Campylobacter bacteriophages. The genomes were extremely similar at the nucleotide level (> or = 96%) with most differences accounted for by novel insertion sequences, DNA methylases and an approximately 10 kb contiguous region of metabolic genes that were dissimilar at the sequence level but similar in gene function between the two phages. Both bacteriophages contained a large number of radical S-adenosylmethionine (SAM) genes, presumably involved in boosting host metabolism during infection, as well as evidence that many genes had been acquired from a wide range of bacterial species. Further bacteriophages, from the UK Campylobacter typing set, were screened for the presence of bacteriophage structural genes, DNA methylases, mobile genetic elements and regulatory genes identified from the genome sequences. The results indicate that many of these bacteriophages are related, with 10 out of 15 showing some relationship to the sequenced genomes. CONCLUSIONS: Two large virulent Campylobacter bacteriophages were found to show very high levels of sequence conservation despite separation in time and place of isolation. The bacteriophages show adaptations to their host and possess genes that may enhance Campylobacter metabolism, potentially advantaging both the bacteriophage and its host. Genetic conservation has been shown to extend to other Campylobacter bacteriophages, forming a highly conserved lineage of bacteriophages that predate upon campylobacters and indicating that highly adapted bacteriophage genomes can be stable over prolonged periods of time

A New Population of High Redshift, Dusty Lyman-Alpha Emitters and Blobs Discovered by WISE

We report a new technique to select 1.6<z<4.6 dusty Lyman-alpha emitters (LAEs), over a third of which are `blobs' (LABs) with emission extended on scales of 30-100kpc. Combining data from the NASA Wide-field Infrared Survey Explorer (WISE) mission with optical spectroscopy from the W.M. Keck telescope, we present a color criteria that yields a 78% success rate in identifying rare, dusty LAEs of which at least 37% are LABs. The objects have a surface density of only ~0.1 per square degree, making them rare enough that they have been largely missed in narrow surveys. We measured spectroscopic redshifts for 92 of these WISE-selected, typically radio-quiet galaxies and find that the LAEs (LABs) have a median redshift of 2.3 (2.5). The WISE photometry coupled with data from Herschel reveals that these galaxies have extreme far-infrared luminosities (L_IR>10^{13-14}L_sun) and warm colors, typically larger than submillimeter-selected galaxies (SMGs) and dust-obscured galaxies (DOGs). These traits are commonly associated with the dust being energized by intense AGN activity. We hypothesize that the combination of spatially extended Lyman-alpha, large amounts of warm IR-luminous dust, and rarity (implying a short-lived phase) can be explained if the galaxies are undergoing strong `feedback' transforming them from an extreme dusty starburst to a QSO.Comment: Submitted to ApJ Letters, 6 pages, 4 figures. Comments welcom