Renal thromboembolism in tako-tsubo cardiomyopathy in spite of anticoagulation

SummaryAn elderly lady was admitted with chest pain and an electrocardiogram depicting ST segment elevation, indicative of a myocardial infarction. She was treated with intra-venous tissue plasminogen activator. On coronary angiography there was a dilated and akinetic left ventricular apex but no significant coronary artery disease. She was diagnosed with tako-tsubo cardiomyopathy. An echocardiogram performed two days later demonstrated a thrombus in the left ventricular apex. Despite immediate anticoagulation with intravenous unfractionated heparin, she sustained a renal thromboembolic phenomenon

Predictors of intention translation in flexible sigmoidoscopy screening for colorectal cancer

Objective: This prospective study aimed to identify predictors of intention and subsequent attendance of flexible sigmoidoscopy screening using constructs derived from the Health Belief Model (HBM). Method: A total of 4,330 people aged 54 years and registered at 1 of 83 participating English general practices were sent a preinvitation questionnaire to assess sociodemographics, HBM variables including perceived benefits, barriers, seriousness, health motivation, and external cues to action as well a range of other constructs and personal characteristics known to relate to cancer screening. Results: Of the 1,578 respondents (36.4%), 1,555 (98.5%) answered the intention question: 52.9% stated definitely yes, 38.1% probably yes, 6.8% probably not, and 2.2% definitely not. Intentions were positively associated with a higher score on a scale of benefits (odds ratio [OR] = 4.62; 95% confidence intervals [CI; 3.24, 6.59]) and health motivation, that is, interest in other ways of preventing colorectal cancer (OR = 2.61; 95% CI [1.62, 4.22]), while a higher score on perceived barriers (OR = 0.19; 95% CI [0.12, 0.31]) and currently following recommended healthy lifestyle behaviors (OR = 0.31; 95% CI [0.16, 0.59]) were negatively associated. Attendance was verified for 922 intenders (65.2%) of whom 737 (79.9%) attended. Attendance was predicted by health motivation (OR = 1.75; 95% CI [1.07, 2.86]), perceived benefits (OR = 1.82; 95% CI [1.37, 2.43]), perceived barriers (OR = 0.47; 95% CI [0.32, 0.69]), individual-level deprivation (OR = 0.26; 95% CI [0.14, 0.50]), and having diabetes (OR = 0.48; 95% CI [0.25, 0.94]). Conclusion: This study supported the usefulness of the HBM in predicting cancer screening and was further enhanced by adding non-HBM variables such as individual socioeconomic deprivation and comorbidities

Barriers to bowel scope (flexible sigmoidoscopy) screening: a comparison of non-responders, active decliners and non-attenders

Background Participation in bowel scope screening (BSS) is low (43%), limiting its potential to reduce colorectal cancer (CRC) incidence and mortality. This study aimed to quantify the prevalence of barriers to BSS and examine the extent to which these barriers differed according to non-participant profiles: non-responders to the BSS invitation, active decliners of the invitation, and non-attenders of confirmed appointments. Methods Individuals invited for BSS between March 2013 and December 2015, across 28 General Practices in England, were sent a questionnaire. Questions measured initial interest in BSS, engagement with the information booklet, BSS participation, and, where applicable, reasons for BSS non-attendance. Chi-square tests of independence were performed to examine the relationship between barriers, non-participant groups and socio-demographic variables. Results 1478 (45.8%) questionnaires were returned for analysis: 1230 (83.2%) attended screening, 114 (7.7%) were non-responders to the BSS invitation, 100 (6.8%) were active decliners, and 34 (2.3%) were non-attenders. Non-responders were less likely to have read the whole information booklet than active decliners (x2 (2, N = 157) = 7.00, p = 0.008) and non-attenders (x2 (2, N = 101) = 8.07, p = 0.005). Non-responders also had lower initial interest in having BSS than either active decliners (x2 (2, N = 213) = 6.07, p = 0.014) or non-attenders (x2 (2, N = 146) = 32.93, p

Uptake of Bowel Scope (Flexible Sigmoidoscopy) Screening in the English National Programme: the first 14 months

Objective To examine uptake in the first six pilot centres of the English Bowel Scope Screening (BSS) programme, which began in early 2013 and invites adults aged 55 for a one off Flexible Sigmoidoscopy. Methods Between March 2013 and May 2014 the six pilot centres sent 21,187 invitations. Using multivariate logistic regression analysis, we examined variation in uptake by gender, socioeconomic deprivation (using the Index of Multiple Deprivation), area-based ethnic diversity (proportion of non-white residents), screening centre, and appointment time (routine: daytime vs out-of-hours: evening/weekend). Results Uptake was 43.1%. Men were more likely to attend than women (45% vs 42%; OR 1.136, 95% CI 1.076, 1.199, p

Platelet inhibition with ticagrelor 60 mg versus 90 mg twice daily in the PEGASUS-TIMI 54 trial

Background The PEGASUS-TIMI 54 (Prevention of Cardiovascular Events in Patients with Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin–Thrombolysis In Myocardial Infarction 54) trial studied 2 doses of ticagrelor, 90 mg twice a day (bid) and 60 mg bid, for long-term prevention of ischemic events in patients with prior myocardial infarction. Both doses similarly reduced the rate of ischemic events versus placebo. The pharmacokinetics and pharmacodynamics of ticagrelor 60 mg bid have not been studied. Objectives In this study, the authors sought to study the pharmacokinetics and pharmacodynamics for ticagrelor 60 mg compared with 90 mg bid. Methods A total of 180 patients who received >4 weeks of study medication had blood sampling in the morning pre-maintenance dose and again 2 h post-dose. All patients received aspirin. Plasma levels of ticagrelor and its active metabolite AR-C124910XX were determined. P2Y12 inhibition was assessed by the VerifyNow P2Y12 assay (Accumetrics, Inc., San Diego, California) (P2Y12 reaction units [PRU]), light transmittance aggregometry (adenosine diphosphate 5 and 20 μmol/l and arachidonic acid), and vasodilator-stimulated phosphoprotein phosphorylation assays. VerifyNow Aspirin assays and serum thromboxane B2 measurements were performed. Results Mean pre- and post-dose plasma levels of ticagrelor were 35% and 38% lower, respectively, with 60 mg versus 90 mg. Both doses achieved high levels of platelet inhibition pre- and post-dose, with numerically slightly more variability with 60 mg: mean (SD) pre-dose PRU values were 59 ± 63 and 47 ± 43 for ticagrelor 60 and 90 mg, respectively (p = 0.34). High platelet reactivity, determined as PRU >208, was rare with the 60-mg pre-dose and was absent post-dose. Platelet reactivity pre- and post-dose, as measured by light transmittance aggregometry or vasodilator-stimulated phosphoprotein assays, was numerically but not significantly lower with 90 mg than with 60 mg. Aspirin response was not affected by either dose. Conclusions Ticagrelor 60 mg bid achieved high levels of peak and trough platelet inhibition in nearly all patients, similar to that with 90 mg bid, helping to explain the efficacy of the lower ticagrelor dose in PEGASUS-TIMI 54

A time and motion study of patients presenting at the accident and emergency department at Mater Dei Hospital

<p>Abstract</p> <p>Background</p> <p>To carry out a time and motion study of patients presenting at the Emergency Department (ED) by measuring waiting times at the ED dept throughout the day. The objectives were:</p> <p indent="1">• to determine whether waiting times are prolonged, and</p> <p indent="1">• if prolonged, at which station(s) bottlenecks occur most often in terms of duration and frequency.</p> <p>Results will be compared to the United Kingdom guidelines of stay at the emergency department.</p> <p>Methods</p> <p>A group of 11 medical students monitored all patients who attended ED between 0600 hours on the 25^thAugust and 0600 hours on the 1st September 2008. For each 24 hour period, students were assigned to the triage room and the 3 priority areas where they monitored all patient-related activity, movement and waiting times so that length of stay (LOS) could be recorded. The key data recorded included patient characteristics, waiting times at various ED process stages, tests performed, specialist consultations and follow up until admitted, discharged, or referred to another hospital area. Average waiting times were calculated for each priority area. Bottle-necks and major limiting factors were identified. Results were compared against the United Kingdom benchmarks - i.e. 1 hour until first assessment, and 4 hours before admitting/discharge.</p> <p>Results</p> <p>1779 patients presented to the ED in the week monitored. As expected, patients in the lesser priority areas (i.e. 2 & 3) waited longer before being assessed by staff. Patients requiring laboratory and imaging investigations had a prolonged length of stay, which varied depending on specific tests ordered. Specialty consultation was associated with longer waiting times. A major bottleneck identified was waiting times for inpatient admission.</p> <p>Conclusions</p> <p>In conclusion, it was found that 30.3% of priority 1 patients, 86.3% of priority 2 patients and 76.8% of priority 3 patients waited more than 1 hour for first assessment. We conclude by proposing several changes that may expedite throughput.</p

The atypical 'hippocampal' glutamate receptor coupled to phospholipase D that controls stretch-sensitivity in primary mechanosensory nerve endings is homomeric purely metabotropic GluK2

ACKNOWLEDGEMENTS We would like to thank: Prof. Christophe Mulle, University of Bordeaux, France for the generous donation of the GluK2-Neo mice; Prof. Roberto Pellicciari and Prof. Maura Marinozzi, University of Perugia, Italy for the generous gift of PCCG-13; the Microscopy and Histology core facility at the Institute of Medical Sciences, University of Aberdeen for their support and assistance in some of the imaging in this work. We would also like to thank Prof. Gernot Riedel, University of Aberdeen UK and Prof. David Jane, University of Bristol UK for helpful comments during the work and discussion about drafts of this manuscript.Peer reviewedPublisher PD

International Expert Consensus on Switching Platelet P2Y(12) Receptor-Inhibiting Therapies

Dual antiplatelet therapy with aspirin and a P2Y(12) inhibitor is the treatment of choice for the prevention of atherothrombotic events in patients with acute coronary syndromes and for those undergoing percutaneous coronary interventions. The availability of different oral P2Y(12) inhibitors (clopidogrel, prasugrel, ticagrelor) has enabled physicians to contemplate switching among therapies because of specific clinical scenarios. The recent introduction of an intravenous P2Y(12) inhibitor (cangrelor) further adds to the multitude of modalities and settings in which switching therapies may occur. In clinical practice, it is not uncommon to switch P2Y(12) inhibitor, and switching may be attributed to a variety of factors. However, concerns about the safety of switching between these agents have emerged. Practice guidelines have not fully elaborated on how to switch therapies, leaving clinicians with limited guidance on when and how to switch therapies when needed. This prompted the development of this expert consensus document by key leaders from North America and Europe with expertise in basic, translational, and clinical sciences in the field of antiplatelet therapy. This expert consensus provides an overview of the pharmacology of P2Y(12) inhibitors, different modalities and definitions of switching, and available literature and recommendations for switching between P2Y(12) inhibitors

Improving the conservation of Mediterranean Chondrichthyans : the ELASMOMED DNA barcode reference library

Cartilaginous fish are particularly vulnerable to anthropogenic stressors and environmental change because of their K-selected reproductive strategy. Accurate data from scientific surveys and landings are essential to assess conservation status and to develop robust protection and management plans. Currently available data are often incomplete or incorrect as a result of inaccurate species identifications, due to a high level of morphological stasis, especially among closely related taxa. Moreover, several diagnostic characters clearly visible in adult specimens are less evident in juveniles. Here we present results generated by the ELASMOMED Consortium, a regional network aiming to sample and DNA-barcode the Mediterranean Chondrichthyans with the ultimate goal to provide a comprehensive DNA barcode reference library. This library will support and improve the molecular taxonomy of this group and the effectiveness of management and conservation measures. We successfully barcoded 882 individuals belonging to 42 species (17 sharks, 24 batoids and one chimaera), including four endemic and several threatened ones. Morphological misidentifications were found across most orders, further confirming the need for a comprehensive DNA barcoding library as a valuable tool for the reliable identification of specimens in support of taxonomist who are reviewing current identification keys. Despite low intraspecific variation among their barcode sequences and reduced samples size, five species showed preliminary evidence of phylogeographic structure. Overall, the ELASMOMED initiative further emphasizes the key role accurate DNA barcoding libraries play in establishing reliable diagnostic species specific features in otherwise taxonomically problematic groups for biodiversity management and conservation actions.peer-reviewe