Trends in Prescribing Oral Anticoagulants in Canada, 2008–2014

AbstractPurposeThe non–vitamin K antagonist oral anticoagulants (NOACs), dabigatran, rivaroxaban, and apixaban, provide several advantages over vitamin K antagonists, such as warfarin. Little is known about the trends of prescribing OACs in Canada. In this study we analyzed changes in prescription volumes for OAC drugs since the introduction of the NOACs in Canada overall, by province and by physician specialty.MethodsCanadian prescription volumes for warfarin, dabigatran, rivaroxaban, and apixaban from January 2008 to June 2014 were obtained from the Canadian Compuscript Audit of IMS Health Canada Inc and were analyzed by physician specialty at the national and provincial levels. Total prescriptions by indication were calculated based on data from the Canadian Disease and Therapeutic Index for all OAC indications and for each commonly prescribed dose of dabigatran (75, 110, and 150 mg), rivaroxaban (10, 15, and 20 mg), and apixaban (2.5 and 5 mg).FindingsThe overall number of OAC prescriptions in Canada has increased annually since 2008. With the availability of the NOACs, the proportion of total OAC prescriptions attributable to warfarin has steadily decreased, from 99% in 2010 to 67% by June 2014, and the absolute number of warfarin prescriptions has been decreasing since February 2011. The greatest decline in proportionate warfarin prescriptions was in Ontario. In general, the increase of NOAC prescriptions coincided with the introduction of provinces’ reimbursement of NOAC prescription costs. The proportion of total OAC prescriptions represented by the NOACs varied by specialty, with the greatest proportionate prescribing found among orthopedic surgeons, cardiologists, and neurologists.ImplicationsSince their approval, the NOACs have represented a growing share of total OAC prescriptions in Canada. This trend is expected to continue because the NOACs are given preference over warfarin in guidelines on stroke prevention in patients with atrial fibrillation, because of growing physician experience, and due to the emergence of potential new indications. An understanding of the current prescribing patterns will help to encourage knowledge translation and possibly influence policy/reimbursement strategies

Phase engineering of controlled entangled number states in a single component Bose-Einstein condensate in a double well

We propose a model for the creation of entangled number states (Schr\"odinger cat states) of a Bose-Einstein condensate in a double well through simple phase engineering. We show that a $\pi$-phase imprinted condensate in a double-well evolves, with a simultaneous change of barrier height, to number states with well defined and controlled entanglement. The cat state generation is understood in terms of the underlying classical phase space dynamics of a $\pi$-phase displaced coherent state put at the hyperbolic fixed point of the separatrix of a physical pendulum. The extremity and sharpness of the final cat state is determined by the initial barrier height and the rate at which it is ramped during the evolution.Comment: 11 pages, 5 figures, Submitted to J. Phys. B (letter to the editor

Challenges in Estimating Insecticide Selection Pressures from Mosquito Field Data

Insecticide resistance has the potential to compromise the enormous effort put into the control of dengue and malaria vector populations. It is therefore important to quantify the amount of selection acting on resistance alleles, their contributions to fitness in heterozygotes (dominance) and their initial frequencies, as a means to predict the rate of spread of resistance in natural populations. We investigate practical problems of obtaining such estimates, with particular emphasis on Mexican populations of the dengue vector Aedes aegypti. Selection and dominance coefficients can be estimated by fitting genetic models to field data using maximum likelihood (ML) methodology. This methodology, although widely used, makes many assumptions so we investigated how well such models perform when data are sparse or when spatial and temporal heterogeneity occur. As expected, ML methodologies reliably estimated selection and dominance coefficients under idealised conditions but it was difficult to recover the true values when datasets were sparse during the time that resistance alleles increased in frequency, or when spatial and temporal heterogeneity occurred. We analysed published data on pyrethroid resistance in Mexico that consists of the frequency of a Ile1,016 mutation. The estimates for selection coefficient and initial allele frequency on the field dataset were in the expected range, dominance coefficient points to incomplete dominance as observed in the laboratory, although these estimates are accompanied by strong caveats about possible impact of spatial and temporal heterogeneity in selection

EC85-219 1985 Nebraska Swine Report

This 1985 Nebraska Swine Report was prepared by the staff in Animal Science and cooperating departments for use in the Extension and Teaching programs at the University of Nebraska-Lincoln. Authors from the following areas contributed to this publication: Swine Nutrition, swine diseases, pathology, economics, engineering, swine breeding, meats, agronomy, and diagnostic laboratory. It covers the following areas: breeding, disease control, feeding, nutrition, economics, housing and meats

Radiosynthesis of (R,S)-[18 F]GE387: A Potential PET Radiotracer for Imaging Translocator Protein 18 kDa (TSPO) with Low Binding Sensitivity to the Human Gene Polymorphism rs6971.

Translocator protein (TSPO) is a biomarker of neuroinflammation, which is a hallmark of many neurodegenerative diseases and has been exploited as a positron emission tomography (PET) target. Carbon-11-labelled PK11195 remains the most applied agent for imaging TSPO, despite its short-lived isotope and low brain permeability. Second-generation radiotracers show variance in affinity amongst subjects (low-, mixed-, and high-affinity binders) caused by the genetic polymorphism (rs6971) of the TSPO gene. To overcome these limitations, a new structural scaffold was explored based on the TSPO pharmacophore, and the analogue with a low-affinity binder/high-affinity binder (LAB/HAB) ratio similar (1.2 vs. 1.3) to that of (R)-[11 C]PK11195 was investigated. The synthesis of the reference compound was accomplished in six steps and 9 % overall yield, and the precursor was prepared in eight steps and 8 % overall yield. The chiral separation of the reference and precursor compounds was performed using supercritical fluid chromatography with >95 % ee. The absolute configuration was determined by circular dichroism. Optimisation of reaction conditions for manual radiolabelling revealed acetonitrile as a preferred solvent at 100 °C. Automation of this radiolabelling method provided R and S enantiomers in respective 21.3±16.7 and 25.6±7.1 % decay-corrected yields and molar activities of 55.8±35.6 and 63.5±39.5 GBq μmol-1 (n=3). Injection of the racemic analogue into a healthy rat confirmed passage through the blood-brain barrier.This work was supported by Medical Research Council (UK) grant awards RG46503 (LM, MH, XZ) and RG70550 (EF), National Institute of Health Research (UK), Cambridge Biomedical Research Unit in Dementia (EF, NKR) and the Herchel Smith Fellowship programme (LQ)

Detection of a MicroRNA Signal in an In Vivo Expression Set of mRNAs

Background. microRNAs (miRNAs) are approximately 21 nucleotide non-coding transcripts capable of regulating gene expression. The most widely studied mechanism of regulation involves binding of a miRNA to the target mRNA. As a result, translation of the target mRNA is inhibited and the mRNA may be destabilized. The inhibitory effects of miRNAs have been linked to diverse cellular processes including malignant proliferation, apoptosis, development, differentiation, and metabolic processes. We asked whether endogenous fluctuations in a set of mRNA and miRNA profiles contain correlated changes that are statistically distinguishable from the many other fluctuations in the data set. Methodology/Principal Findings. RNA was extracted from 12 human primary brain tumor biopsies. These samples were used to determine genome-wide mRN

Impact of vaccination on the association of COVID-19 with cardiovascular diseases:An OpenSAFELY cohort study

Infection with SARS-CoV-2 is associated with an increased risk of arterial and venous thrombotic events, but the implications of vaccination for this increased risk are uncertain. With the approval of NHS England, we quantified associations between COVID-19 diagnosis and cardiovascular diseases in different vaccination and variant eras using linked electronic health records for ~40% of the English population. We defined a 'pre-vaccination' cohort (18,210,937 people) in the wild-type/Alpha variant eras (January 2020-June 2021), and 'vaccinated' and 'unvaccinated' cohorts (13,572,399 and 3,161,485 people respectively) in the Delta variant era (June-December 2021). We showed that the incidence of each arterial thrombotic, venous thrombotic and other cardiovascular outcomes was substantially elevated during weeks 1-4 after COVID-19, compared with before or without COVID-19, but less markedly elevated in time periods beyond week 4. Hazard ratios were higher after hospitalised than non-hospitalised COVID-19 and higher in the pre-vaccination and unvaccinated cohorts than the vaccinated cohort. COVID-19 vaccination reduces the risk of cardiovascular events after COVID-19 infection. People who had COVID-19 before or without being vaccinated are at higher risk of cardiovascular events for at least two years.</p