Age structure, dispersion and diet of a population of stoats (Mustela erminea) in southern Fiordland during the decline phase of the beechmast cycle

The dispersion, age structure and diet of stoats (Mustela erminea) in beech forest in the Borland and Grebe Valleys, Fiordland National Park, were examined during December and January 2000/01, 20 months after a heavy seed-fall in 1999. Thirty trap stations were set along a 38-km transect through almost continuous beech forest, at least 1 km apart. Mice were very scarce (nights, C/100TN) along two standard index lines placed at either end of the transect, compared with November 1999 (>60/100TN), but mice were detected (from footprints in stoat tunnels) along an 8 km central section of the transect (stations 14-22). Live trapping with one trap per station (total 317.5 trap nights) in December 2000 caught 2 female and 23 male stoats, of which 10 (including both females) were radio collared. The minimum range lengths of the two females along the transect represented by the trap line were 2.2 and 6.0 km; those of eight radio-tracked males averaged 2.9 ± 1.7 km. Stations 14-22 tended to be visited more often, by more marked individual stoats, than the other 21 stations. Fenn trapping at the same 30 sites, but with multiple traps per station (1333.5 trap nights), in late January 2001 collected carcasses of 35 males and 28 females (including 12 of the marked live-trapped ones). Another two marked males were recovered dead. The stoat population showed no sign of chronic nutritional stress (average fat reserve index = 2.8 on a scale of 1-4 where 4 = highest fat content); and only one of 63 guts analysed was empty. Nevertheless, all 76 stoats handled were adults with 1-3 cementum annuli in their teeth, showing that reproduction had failed that season. Prey categories recorded in descending frequency of occurrence were birds, carabid beetle (ground beetle), weta, possum, rat, and mouse. The frequencies of occurrence of mice and birds in the diet of these stoats (10% and 48%, respectively) were quite different from those in stoats collected in Pig Creek, a tributary of the Borland River (87%, 5%), 12 months previously when mice were still abundant. Five of the six stoat guts containing mice were collected within 1 km of stations 14-22

Use of cardiovascular registries in regulatory pathways:perspectives from the EU-MDR Cardiovascular Collaboratory

On May 26, 2021, the European Medical Device Regulation (EU-MDR) entered into effect resulting in a major shift in the requirements for assessment of medical devices in Europe. The EU-MDR Cardiovascular Collaboratory (EU-MCVC) was founded to contribute to the development of faster, more efficient, and more effective pathways for innovation of cardiac medical devices. A registry is an organized system that collects uniform data and evaluates specified outcomes in a population defined by a disease, condition, or exposure. Most registries have been created to improve the quality of care and provide feedback to physicians, hospitals, and health providers. Clinical registries represent an ideal construct for scientific, clinical, and policy-making collaboration. We describe diverse experiences from 5 European countries and address the traditional quality components in clinical trials. Continued collaboration is expected among academics, clinical trialists, patient representatives, regulatory experts, research organizations, registry platforms, regulatory bodies, and industry partners. Data quality is a primary concern and registry leaders need to optimize data quality to become regulatory compliant. A collaborative approach among medical device stakeholders may improve quality of care, reduce costs, and provide faster access to innovative technologies, with the common objective of improving cardiovascular care and outcomes

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

Comparison of four clinical risk scores in comatose patients after out-of-hospital cardiac arrest.

BACKGROUND AND AIMS Several different scoring systems for early risk stratification after out-of-hospital cardiac arrest have been developed, but few have been validated in large datasets. The aim of the present study was to compare the well-validated Out-of-hospital Cardiac Arrest (OHCA) and Cardiac Arrest Hospital Prognosis (CAHP)-scores to the less complex MIRACLE2- and Target Temperature Management (TTM)-scores. METHODS This was a post-hoc analysis of the Targeted Hypothermia versus Targeted Normothermia after Out-of-Hospital Cardiac Arrest (TTM2) trial. Missing data were handled by multiple imputation. The primary outcome was discriminatory performance assessed as the area under the receiver operating characteristics-curve (AUROC), with the outcome of interest being poor functional outcome or death (modified Rankin Scale 4-6) at 6 months after OHCA. RESULTS Data on functional outcome at 6 months were available for 1829 cases, which constituted the study population. The pooled AUROC for the MIRACLE2-score was 0.810 (95% CI 0.790 - 0.828), 0.835 (95% CI 0.816 - 0.852) for the TTM-score, 0.820 (95% CI 0.800 - 0.839) for the CAHP-score and 0.770 (95% CI 0.748 - 0.791) for the OHCA-score. At the cut-offs needed to achieve specificities >95%, sensitivities were <40 % for all four scoring systems. CONCLUSIONS The TTM-, MIRACLE2- and CAHP-scores are all capable of providing objective risk estimates accurate enough to be used as part of a holistic patient assessment after OHCA of a suspected cardiac origin. Due to its simplicity, the MIRACLE2-score could be a practical solution for both clinical application and risk stratification within trials

A pharmacodynamic comparison of prasugrel vs. high-dose clopidogrel in patients with type 2 diabetes mellitus and coronary artery disease: results of the Optimizing anti-Platelet Therapy In diabetes MellitUS (OPTIMUS)-3 Trial

Aims: Patients with diabetes mellitus (DM) have increased platelet reactivity and reduced platelet response to clopidogrel compared with patients without DM. Prasugrel, a more potent antiplatelet agent, is associated with greater reductions in ischaemic events compared with clopidogrel, particularly in patients with DM. The aim of this study was to perform serial pharmacodynamic assessments of prasugrel with high-dose clopidogrel in patients with DM. Methods and results: Optimizing anti-Platelet Therapy In diabetes MellitUS (OPTIMUS)-3 was a prospective, randomized, double-blind, crossover study in patients with type 2 DM and coronary artery disease (CAD). Patients (n= 35) were randomly assigned to either prasugrel 60 mg loading dose (LD)/10 mg maintenance dose (MD) or clopidogrel 600 mg LD/150 mg MD over two 1-week treatment periods separated by a 2-week washout period. Platelet function was assessed by VerifyNow® P2Y12 assay, light transmission aggregometry, and vasodilator-stimulated phosphoprotein phosphorylation at 0, 1, 4, and 24 h and 7 days. Greater platelet inhibition by VerifyNow® P2Y12 was achieved by prasugrel compared with clopidogrel at 4 h post-LD (least squares mean, 89.3 vs. 27.7%, P< 0.0001; primary endpoint). The difference in platelet inhibition between prasugrel and clopidogrel was significant from 1 h through 7 days (P < 0.0001). Similar results were obtained using all other platelet function measures. Prasugrel resulted in fewer poor responders at all time points irrespective of definition used. Conclusion: In patients with type 2 DM and CAD, standard-dose prasugrel is associated with greater platelet inhibition and better response profiles during both the loading and maintenance periods when compared with double-dose clopidogrel

Calcium phosphate particles stimulate interleukin-1β release from human vascular smooth muscle cells: A role for spleen tyrosine kinase and exosome release

Aims: Calcium phosphate (CaP) particle deposits are found in several inflammatory diseases including atherosclerosis and osteoarthritis. CaP, and other forms of crystals and particles, can promote inflammasome formation in macrophages leading to caspase-1 activation and secretion of mature interleukin-1β (IL-1β). Given the close association of small CaP particles with vascular smooth muscle cells (VSMCs) in atherosclerotic fibrous caps, we aimed to determine if CaP particles affected pro-inflammatory signalling in human VSMCs. Methods and results: Using ELISA to measure IL-1β release from VSMCs, we demonstrated that CaP particles stimulated IL-1β release from proliferating and senescent human VSMCs, but with substantially greater IL-1β release from senescent cells; this required caspase-1 activity but not LPS-priming of cells. Potential inflammasome agonists including ATP, nigericin and monosodium urate crystals did not stimulate IL-1β release from VSMCs. Western blot analysis demonstrated that CaP particles induced rapid activation of spleen tyrosine kinase (SYK) (increased phospho-Y525/526). The SYK inhibitor R406 reduced IL-1β release and caspase-1 activation in CaP particle-treated VSMCs, indicating that SYK activation occurs upstream of and is required for caspase-1 activation. In addition, IL-1β and caspase-1 colocalised in intracellular endosome-like vesicles and we detected IL-1β in exosomes isolated from VSMC media. Furthermore, CaP particle treatment stimulated exosome secretion by VSMCs in a SYK-dependent manner, while the exosome-release inhibitor spiroepoxide reduced IL-1β release. Conclusions: CaP particles stimulate SYK and caspase-1 activation in VSMCs, leading to the release of IL-1β, at least in part via exosomes. These novel findings in human VSMCs highlight the pro-inflammatory and procalcific potential of microcalcification

Prognostic utility and characterization of left ventricular hypertrophy using global thickness

Cardiovascular magnetic resonance (CMR) can accurately measure left ventricular (LV) mass, and several measures related to LV wall thickness exist. We hypothesized that prognosis can be used to select an optimal measure of wall thickness for characterizing LV hypertrophy. Subjects having undergone CMR were studied (cardiac patients, n = 2543; healthy volunteers, n = 100). A new measure, global wall thickness (GT, GTI if indexed to body surface area) was accurately calculated from LV mass and end-diastolic volume. Among patients with follow-up (n = 1575, median follow-up 5.4 years), the most predictive measure of death or hospitalization for heart failure was LV mass index (LVMI) (hazard ratio (HR)[95% confidence interval] 1.16[1.12–1.20], p < 0.001), followed by GTI (HR 1.14[1.09–1.19], p < 0.001). Among patients with normal findings (n = 326, median follow-up 5.8 years), the most predictive measure was GT (HR 1.62[1.35–1.94], p < 0.001). GT and LVMI could characterize patients as having a normal LV mass and wall thickness, concentric remodeling, concentric hypertrophy, or eccentric hypertrophy, and the three abnormal groups had worse prognosis than the normal group (p < 0.05 for all). LV mass is highly prognostic when mass is elevated, but GT is easily and accurately calculated, and adds value and discrimination amongst those with normal LV mass (early disease)

Standardized EEG interpretation accurately predicts prognosis after cardiac arrest.

OBJECTIVE: To identify reliable predictors of outcome in comatose patients after cardiac arrest using a single routine EEG and standardized interpretation according to the terminology proposed by the American Clinical Neurophysiology Society. METHODS: In this cohort study, 4 EEG specialists, blinded to outcome, evaluated prospectively recorded EEGs in the Target Temperature Management trial (TTM trial) that randomized patients to 33°C vs 36°C. Routine EEG was performed in patients still comatose after rewarming. EEGs were classified into highly malignant (suppression, suppression with periodic discharges, burst-suppression), malignant (periodic or rhythmic patterns, pathological or nonreactive background), and benign EEG (absence of malignant features). Poor outcome was defined as best Cerebral Performance Category score 3-5 until 180 days. RESULTS: Eight TTM sites randomized 202 patients. EEGs were recorded in 103 patients at a median 77 hours after cardiac arrest; 37% had a highly malignant EEG and all had a poor outcome (specificity 100%, sensitivity 50%). Any malignant EEG feature had a low specificity to predict poor prognosis (48%) but if 2 malignant EEG features were present specificity increased to 96% (p &lt; 0.001). Specificity and sensitivity were not significantly affected by targeted temperature or sedation. A benign EEG was found in 1% of the patients with a poor outcome. CONCLUSIONS: Highly malignant EEG after rewarming reliably predicted poor outcome in half of patients without false predictions. An isolated finding of a single malignant feature did not predict poor outcome whereas a benign EEG was highly predictive of a good outcome