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Objectives:This study aimed to ascertain otolaryngologists’ current knowledge of new (e.g. apixaban, rivaroxaban) and old (e.g. warfarin) anticoagulant medications, and to provide an educational overview of new anticoagulants for use by surgeons.Methods:A questionnaire survey was distributed across the Wessex region, UK, to ascertain the levels of knowledge of and confidence in managing patients taking various anticoagulants. In total, 50 questionnaires were completed (41 by trainees and 9 by consultants). A literature review of new anticoagulant medications was then conducted.Results:In general, there was poor clinical and pharmacokinetic knowledge of newly licensed anticoagulant medications. Respondents were more confident in the use of older vs newer forms of anticoagulants. This was true across all grades of doctors, but particularly at the senior level. All respondents stated that they would like to see an educational resource on anticoagulants.Conclusion:Knowledge of newly licensed anticoagulation medications is poor. This study has produced an educational resource for the management of anticoagulant agents. A thorough knowledge of these drugs is essential for the acute management of bleeding patients and in peri-operative surgical planning. [ABSTRACT FROM PUBLISHER]

The conclusions of the European Food Safety Authority (EFSA) following the peer review of the initial risk assessments carried out by the competent authority of the rapporteur Member State the United Kingdom and the co-rapporteur Member State France for the pesticide active substance cyantraniliprole and the assessment of applications for maximum residue levels (MRLs) are reported. The context of the peer review was that required by Regulation (EC) No 1107/2009 of the European Parliament and of the Council. The conclusions were reached on the basis of the evaluation of the representative uses of cyantraniliprole as an insecticide on various crops in agriculture and horticulture. MRLs were assessed in oranges, mandarins, apples/pears, peaches, apricots, plums, vine grapes, potatoes, tomatoes, cucumber/courgettes, melon, lettuce, beans and olives. The reliable endpoints concluded as being appropriate for use in regulatory risk assessment and the proposed MRLs, derived from the available studies and literature in the dossier peer reviewed, are presented. Missing information identified as being required by the regulatory framework is listed. Concerns are identified. [ABSTRACT FROM AUTHOR]

Objective: To compare real-world effectiveness and safety of direct oral anticoagulants (DOACs) in patients with nonvalvular atrial fibrillation (AFib) for prevention of stroke., Study Design and Setting: A comparative cohort study in UK general practice data from The Health Improvement Network database., Participants and Interventions: Before matching, 5655 patients ≥18 years with nonvalvular AFib who initiated at least one DOAC between 1 July 2014 and 31 December 2020 were included. DOACs of interest included apixaban, rivaroxaban, edoxaban and dabigatran, with the primary comparison between apixaban and rivaroxaban. Initiators of DOACs were defined as new users with no record of prescription for any DOAC during 12 months before index date., Primary and Secondary Outcome Measures: The primary outcome was stroke (ischaemic or haemorrhagic). Secondary outcomes included the occurrence of all-cause mortality, myocardial infarction (MI), transient ischaemic attacks (TIA), major bleeding events and a composite angina/MI/stroke (AMS) endpoint., Results: Compared with rivaroxaban, patients initiating apixaban showed similar rates of stroke (HR: 0.93; 95% CI 0.64 to 1.34), all-cause mortality (HR: 1.03; 95% CI 0.87 to 1.22), MI (HR: 0.95; 95% CI 0.54 to 1.68), TIA (HR: 1.03; 95% CI 0.61 to 1.72) and AMS (HR: 0.96; 95% CI 0.72 to 1.27). Apixaban initiators showed lower rates of major bleeding events (HR: 0.60; 95% CI 0.47 to 0.75)., Conclusions: Among patients with nonvalvular AFib, apixaban was as effective as rivaroxaban in reducing rate of stroke and safer in terms of major bleeding episodes. This head-to-head comparison supports conclusions drawn from indirect comparisons of DOAC trials against warfarin and demonstrates the potential for real-world evidence to fill evidence gaps and reduce uncertainty in both health technology assessment decision-making and clinical guideline development., Competing Interests: Competing interests: AJ, LG, AA, AP and NG are employed by and have ownership stake and/or hold stock options in Aetion. Inc. NG holds stock in Pfizer Inc. SK, SR, SD, MS, LK and PJ are employees of the National Institute for Health and Care Excellence. PJ is on the board of the GetReal Institute, which receives grants from Innovative Medicines and Horizon Europe., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Neutrophils play a crucial role in the pathophysiology of rheumatoid arthritis (RA) via the release of reactive oxygen species (ROS), proteases and cytokines. Orally active Janus kinase (JAK) inhibitors (JAKi), e.g. baricitinib and tofacitinib, have high clinical efficacy in RA but are linked with neutropenia and increased infections. Our aim was to determine the effect of JAK inhibition with baricitinib and tofacitinib on healthy control and RA neutrophil lifespan and function. RA (n = 7) and healthy control (n = 7) neutrophils were treated with baricitinib or tofacitinib for 30 min, prior to incubation in the absence or presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) or interferon (IFN)-γ. JAKi prevented GM-CSF- and IFN-γ-induced apoptosis delay in RA and healthy control neutrophils in a dose-dependent manner. Baricitinib decreased the rate of chemotaxis towards interleukin (IL)-8, but not f-Met-Leu-Phe (fMLP) in RA neutrophils. While healthy control neutrophils incubated with GM-CSF became primed to produce ROS in response to stimulation with fMLP and phorbol-12-myristate-12-acetate (PMA), RA neutrophils produced increased levels of ROS without the need for priming. JAKi prevented ROS release from primed healthy control neutrophils in response to fMLP, but had no effect on ROS production by RA neutrophils. Baricitinib reversed GM-CSF priming of ROS production in response to fMLP in healthy control, but not RA, neutrophils. We conclude that incubation with JAKi prevents chemotaxis of RA neutrophils towards IL-8, but does not prevent the production of ROS or increase the level of apoptosis. This may be due to the in-vivo exposure of RA neutrophils to priming agents other than those that activate JAK/signal transducer and activator of transcription (STAT) signalling., (© 2017 British Society for Immunology.)