Ticagrelor versus clopidogrel in patients with acute coronary syndromes and chronic obstructive pulmonary disease: An analysis from the platelet inhibition and patient outcomes (PLATO) trial

Background Patients with chronic obstructive pulmonary disease (COPD) experiencing acute coronary syndromes (ACS) are at high risk for clinical events. In the Platelet Inhibition and Patient Outcomes (PLATO) trial, ticagrelor versus clopidogrel reduced the primary endpoint of death from vascular causes, myocardial infarction, or stroke after ACS, but increased the incidence of dyspnea, which may lead clinicians to withhold ticagrelor from COPD patients. Methods and Results In 18 624 patients with ACS randomized to treatment with ticagrelor or clopidogrel, history of COPD was recorded in 1085 (5.8%). At 1 year, the primary endpoint occurred in 17.7% of patients with COPD versus 10.4% in those without COPD (P<0.001). The 1‐year event rate for the primary endpoint in COPD patients treated with ticagrelor versus clopidogrel was 14.8% versus 20.6% (hazard ratio [HR]=0.72; 95% confidence interval [CI]: 0.54 to 0.97), for death from any cause 8.4% versus 12.4% (HR=0.70; 95% CI: 0.47 to 1.04), and for PLATO‐defined major bleeding rates at 1 year 14.6% versus 16.6% (HR=0.85; 95% CI: 0.61 to 1.17). Dyspnea occurred more frequently with ticagrelor (26.1% vs. 16.3%; HR=1.71; 95% CI: 1.28 to 2.30). There was no differential increase in the relative risk of dyspnea compared to non‐COPD patients (HR=1.85). No COPD status‐by‐treatment interactions were found, showing consistency with the main trial results. Conclusions In this post‐hoc analysis, COPD patients experienced high rates of ischemic events. Ticagrelor versus clopidogrel reduced and substantially decreased the absolute risk of ischemic events (5.8%) in COPD patients, without increasing overall major bleeding events. The benefit‐risk profile supports the use of ticagrelor in patients with ACS and concomitant COPD. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00391872

The western painted turtle genome, a model for the evolution of extreme physiological adaptations in a slowly evolving lineage

Background: We describe the genome of the western painted turtle, Chrysemys picta bellii, one of the most widespread, abundant, and well-studied turtles. We place the genome into a comparative evolutionary context, and focus on genomic features associated with tooth loss, immune function, longevity, sex differentiation and determination, and the species' physiological capacities to withstand extreme anoxia and tissue freezing.Results: Our phylogenetic analyses confirm that turtles are the sister group to living archosaurs, and demonstrate an extraordinarily slow rate of sequence evolution in the painted turtle. The ability of the painted turtle to withstand complete anoxia and partial freezing appears to be associated with common vertebrate gene networks, and we identify candidate genes for future functional analyses. Tooth loss shares a common pattern of pseudogenization and degradation of tooth-specific genes with birds, although the rate of accumulation of mutations is much slower in the painted turtle. Genes associated with sex differentiation generally reflect phylogeny rather than convergence in sex determination functionality. Among gene families that demonstrate exceptional expansions or show signatures of strong natural selection, immune function and musculoskeletal patterning genes are consistently over-represented.Conclusions: Our comparative genomic analyses indicate that common vertebrate regulatory networks, some of which have analogs in human diseases, are often involved in the western painted turtle's extraordinary physiological capacities. As these regulatory pathways are analyzed at the functional level, the painted turtle may offer important insights into the management of a number of human health disorders

Biological, chemical and physical characteristics of downwelling and upwelling zones in the hyporheic zone of a north-temperate stream

Along a single stream riffle, there is a typical flow pattern in which surface water enters the hyporheic zone in a downwelling zone at the head of the riffle and hyporheic water returns to the stream surface in an upwelling zone at the tail of the riffle. Distinct patterns of physical and chemical conditions in the hyporheic zone are likely to determine patterns of microbial activity and occurrence of hyporheic fauna. Interstitial water and core samples were taken at three depths in the downwelling and upwelling zones of a single riffle in the Speed River, Southern Ontario, Canada. Physical and chemical characteristics of the hyporheic water, bacterial density, protein content, detritus content and faunal composition of the hyporheic sediment were analysed. The downwelling and upwelling zones differed significantly in temperature, pH, redox potential, dissolved oxygen and nitrate with significant positive correlations occurring among the latter three. There were no differences in bacterial density or detritus content between the two zones nor between depths in either zone, but protein content, considered to be a measure of biofilm biomass, was significantly higher in the downwelling zone. Total density of hyporheic fauna and the number of taxa decreased with increasing depth in both upwelling and downwelling zones, and were positively correlated with surface water characteristics (oxygen, temperature and nitrate), sediment protein content and detritus; however, only a weak correlation was found with zone. The composition of taxa differed between the two zones, and faunal distribution was correlated with dissolved oxygen, detritus, protein content and dept

CORRTEX: a compact and versatile system for time domain reflectometry

The CORRTEX (COntinuous Reflectometry for Radius versus Time EXperiments) system was designed to be an adaptable and versatile unit for performing time domain reflectometry (TDR). The system consists of a coaxial cable, a digital TDR, which uses a Motorola 6800 microprocessor, a power source or battery pack, and an output terminal or recording driver. Desirable criteria for the system are discussed as well as the operation of the CORRTEX system. The types of present applications of the CORRTEX system are summarized and data presented

Biochemistry below 0°C: Nature's frozen vertebrates

Although alien to man, the ability to endure the freezing of extra-cellular body fluids during the winter has developed in several species of terrestrially hibernating frogs and turtles as well as in many species of insects and other invertebrates. Wood frogs, for example, can endure freezing for at least 2 weeks with no breathing, no heart beat or blood circulation, and with up to 65% of their total body water as ice. Our studies are providing a comprehensive view of the requirements for natu

Multicenter randomized trial of intermittently scanned continuous glucose monitoring versus self-monitoring of blood glucose in individuals with type 2 diabetes and recent-onset acute myocardial infarction: results of the LIBERATES trial

OBJECTIVE To analyze the impact of modern glucose-monitoring strategies on glycemic and patient-related outcomes in individuals with type 2 diabetes (T2D) and recent myocardial infarction (MI) and assess cost effectiveness. RESEARCH DESIGN AND METHODS LIBERATES was a multicenter two-arm randomized trial comparing self-monitoring of blood glucose (SMBG) with intermittently scanned continuous glucose monitoring (isCGM), also known as flash CGM, in individuals with T2D and recent MI, treated with insulin and/or a sulphonylurea before hospital admission. The primary outcome measure was time in range (TIR) (glucose 3.9–10 mmol/L/day) on days 76–90 post randomization. Secondary and exploratory outcomes included time in hypoglycemia, hemoglobin A1c (HbA1c), clinical outcome, quality of life (QOL), and cost effectiveness. RESULTS Of 141 participants randomly assigned (median age 63 years; interquartile range 53, 70), 73% of whom were men, isCGM was associated with increased TIR by 17 min/day (95% credible interval −105 to +153 min/day), with 59% probability of benefit. Users of isCGM showed lower hypoglycemic exposure (<3.9 mmol/L) at days 76–90 (−80 min/day; 95% CI −118, −43), also evident at days 16–30 (−28 min/day; 95% CI −92, 2). Compared with baseline, HbA1c showed similar reductions of 7 mmol/mol at 3 months in both study arms. Combined glycemic emergencies and mortality occurred in four isCGM and seven SMBG study participants. QOL measures marginally favored isCGM, and the intervention proved to be cost effective. CONCLUSIONS Compared with SMBG, isCGM in T2D individuals with MI marginally increases TIR and significantly reduces hypoglycemic exposure while equally improving HbA1c, explaining its cost effectiveness. Studies are required to understand whether these glycemic differences translate into longer-term clinical benefit