Therapeutic achievement with long-term oral anticoagulants in post-myocardial infarction patients

Treatment with oral anticoagulant therapy entails a delicate balance between over( risk of bleeding) and under- (risk of thrombemboli) anticoagulation. Therapy is therefore monitored to maintain its anticoagulant effect within a narrow range. The main aim of this research was to determine the optimal intensity of long-term anticoagulant therapy in 3404 post-myocardial infarction patients. Chapter 1 gives a review of long-term clinical trials which assessed the mertts of anticoagulant therapy in the secondary prevention of morbidity and mortality after myocardial infarction. This review includes the results of more than thirty trials reported in the literature in the past forty years, however, unpublished data or results of small trials, were not considered. Few of these trials were randomized, and the level of anticoagulation was properly maintained in only some of these studies. The results of most of these trials have failed to convincingly demonstrate the beneficial effects of long-term anticoagulant therapy as a secondary preventive measure and the use of such therapy has therefore remained controversial. Chapters 2 and 3 describe the design and execution of the ASPECT (Anticoagulants in the Secondary Prevention of Events in Coronary Thrombosis) trial. The main results of this trial are submitted in Appendix-A. ASPECT was designed to be a randomized, double-blind, placebo controlled, multicentre trial which compared standard oral anticoagulant therapy with placebo with regards to mortality and cardiovascular events. Chapter 2 describes the design and procedures of the ASPECT trial in detail, in particular the methods for double-blind anticoagulant titration. Chapter 3 presents an outline of the data processing system as used in ASPECT. A standardized procedure which was developed for data handling insured a high level of data quality derived from the participating centres. Chapters 4, 5 and 6 addresses the effectiveness and safety of oral anticoagulant therapy. Chapter 4 reviews various methods, previously described, to evaluate therapeutic achievement of anticoagulant therapy in the ASPECT trial. In Chapter 5, the optimal achieved intensity of anticoagulant therapy required to prevent recurrence of arterial thromboembolic and haemorrhagic complications was quantitatively evaluated with regard to the international normalized ratio (INR) intensity preceding the event, enabling the calculation of INR-specific incidence rates. The INR expresses the level of anticoagulant therapy in an internationally agreed term. It is the common term for the prothrombin time as measured in a patient on oral anticoagulant therapy. Chapter 6 gives a detailed description of the risk of stroke in the ASPECT population. Finally, a discussion of the findings is provided in Chapter 7, followed by recommendations for further researc

Inter- and intra-observer variability in the qualitative categorization of coronary angiograms.

The ABC classification of the American College of Cardiology and the American Heart Association is a commonly used categorization to estimate the risk and success of intracoronary intervention, as well as the probability of restenosis. To evaluate the reliability of qualitative angiogram readings, we randomly selected 200 films from single lesion angioplasty procedures. A repeated visual assessment (> or = 2 months interval) by two independent observers resulted in kappa values of inter and intra-observer variability for the ABC lesion classification and for all separate items that compile it. Variability in assessment is expressed in percentage of total agreement, and in kappa value, which is a parameter of the agreement between two or more observations in excess of the chance agreement. Percentage of total agreement and kappa value was 67.8% and 0.33 respectively for the ABC classification, indicating a poor agreement. Probably this is due to the deficiency of strict definitions. Further investigation has to demonstrate whether improvement can be achieved using complete and detailed definitions without ambiguity, and consensus after panel assessment

Optimal intensity of oral anticoagulant therapy after myocardial infarction

AbstractObjectives.This study attempted to determine the optimal intensity of anticoagulant therapy in patients after myocardial infarction.Background.Treatment with oral anticoagulant therapy entails a delicate balance between over- (risk of bleeding) and under-anticoagulant (risk of thromboemboli). The optimal intensity required to prevent the occurrence of either event (bleeding or thromboembolic) is not known.Methods.A method was used to determine the optimal intensity of anticoagulant therapy by calculating incidence rates for either event associated with a specific international normalized ratio. The numerator included events occurring at given international normalized ratios, and the denominator comprised the total observation time.Results.The study population included 3,404 myocardial infarction patients enrolled in the ASPECT (anticoagulants in the Secondary Prevention of Events in Coronary Thrombosis) trial. Total treatment was 6,918 patient-years. Major bleeding occurred in 57 patients (0.8/100 patient-years), and thromboembolic complications in 397 (5.7/100 patient-years). The incidence of the combined outcome (bleeding or thromboembolic complications) with international normalized ratio < 2 was 8.0/100 patient-years (283 events in 3,559 patient-years), with international normalized ratios between 2 and 3, 3.9/100 patient-years (33 events in 838 patient-years); 3.2/100 patient-years (57 events in 1,775 patient-years) for international normalized ratios between 3 and 4; 6.6/100 patient-years (37 events in 564 patient-years) for international normalized ratios between 4 and 5; and 7.7/100 patient-years (14 events in 182 patient-years) for international normalized ratios >5. After adjustment for achieved international normalized ratio levels, significant predictors were higher levels of systolic blood pressure and age.Conclusions.If equal weight is given to hemorrhagic and thromboembolic complications, these results suggest that the optimal intensity of long-term anticoagulant therapy for myocardial infarction patients lies between 2.0 and 4.0 international normalized ratio, with a trend to suggest an optimal intensity of 3.0 to 4.0

The Inherent Tracer Fingerprint of Captured CO2.

Carbon capture and storage (CCS) is the only currently available technology that can directly reduce anthropogenic CO2 emissions arising from fossil fuel combustion. Monitoring and verification of CO2 stored in geological reservoirs will be a regulatory requirement and so the development of reliable monitoring techniques is essential. The isotopic and trace gas composition - the inherent fingerprint - of captured CO2 streams is a potentially powerful, low cost geochemical technique for tracking the fate of injected gas in CCS projects; carbon and oxygen isotopes, in particular, have been used as geochemical tracers in a number of pilot CO2 storage sites, and noble gases are known to be powerful tracers of natural CO2 migration. However, the inherent tracer fingerprint in captured CO2 streams has yet to be robustly investigated and documented and key questions remain, including how consistent is the fingerprint, what controls it, and will it be retained en route to and within the storage reservoir? Here we present the first systematic measurements of the carbon and oxygen isotopes and the trace noble gas composition of anthropogenic CO2 captured from combustion power stations and fertiliser plants. The analysed CO2 is derived from coal, biomass and natural gas feedstocks, using amine capture, oxyfuel and gasification processes, from six different CO2 capture plants spanning four different countries. We find that δ13C values are primarily controlled by the δ13C of the feedstock while δ18O values are predominantly similar to atmospheric O2. Noble gases are of low concentration and exhibit relative element abundances different to expected reservoir baselines and air, with isotopic compositions that are similar to air or fractionated air. The use of inherent tracers for monitoring and verification was provisionally assessed by analysing CO2 samples produced from two field storage sites after CO2 injection. These experiments at Otway, Australia, and Aquistore, Canada, highlight the need for reliable baseline data. Noble gas data indicates noble gas stripping of the formation water and entrainment of Kr and Xe from an earlier injection experiment at Otway, and inheritance of a distinctive crustal radiogenic noble gas fingerprint at Aquistore. This fingerprint can be used to identify unplanned migration of the CO2 to the shallow subsurface or surface

A comparison of methods of analysing exercise tests for diagnosis of coronary artery disease

The diagnostic accuracy of the following methods of analysing exercise tests were evaluated: (a) the cumulative area of ST segment depression during exercise normalised for workload and heart rate (exercise score); (b) discriminant analysis of electrocardiographic exercise variables, workload, and symptoms; and (c) ST segment amplitude changes during exercise adjusted for heart rate. Three hundred and forty five men without a history of myocardial infarction were studied. One hundred and twenty three were apparently healthy. Less than half (170) had coronary artery disease. All had a normal electrocardiogram at rest. A Frank lead electrocardiogram was computer processed during symptom limited bicycle ergometry. The accuracy of the exercise score (a) was low (sensitivity 67%, specificity 90%). Discriminant analysis (b) and ST segment amplitude changes adjusted for heart rate (c) had excellent diagnostic characteristics (sensitivity 80%, specificity 90%), which were little affected by concomitant use of beta blockers. Both methods seem well suited for diagnostic application in clinical practice

On Approximating the Number of Bases of Exchange Preserving Matroids

We consider the expansion property for the bases-exchange graph of a matroid, which gives an effective randomized approximation scheme for the number of bases. Mihail and Feder in [6] proved that this property holds for the class of so-called balanced matroids, including all regular matroids. We present a much simpler proof of similar result for all matroids satisfying exchange-preservation property, de ned as some graph-theoretic condition on the family of internal exchange graphs. We apply a method of bounding path congestion proposed in [8], which is of additional interest as it was suggested in [6] that this technique seems to be unsuitable to matroid related graphs. As an illustrating example we apply our results to a subclass of transversal matroids

Coronary angioplasty for unstable angina: immediate and late results in 200 consecutive patients with identification of risk factors for unfavorable early and late outcome

Two hundred patients (mean age 56 years, range 36 to 74) with unstable angina (chest pain at rest, associated with ST-T changes) underwent coronary angioplasty. In 65 patients with multivessel disease, only the "culprit" lesion was dilated. The initial success rate was 89.5% (179 of 200 patients). At least one major procedure-related complication occurred in 21 patients (10.5%): (death in 1, myocardial infarction in 16 and urgent surgery in 18). All patients were followed up for 2 years. Five patients died late; 8 had a late nonfatal myocardial infarction and 52 had recurrence of angina pectoris. The restenosis rate was 32% (51 of 158) in the patients with initial successful angioplasty who had repeat angiography. At the 2 year follow-up, after attempted coronary angioplasty in all 200 patients, the total incidence rate of death was 3% (one procedure related; five late deaths), of nonfatal myocardial infarction 12% (16 procedure related and 8 late after angioplasty), and 13% (26 patients) were still symptomatic although they had improved in functional class. Multivariate analysis showed that variables indicating an increased risk 1) for major procedure-related complications were: ST segment elevation, persistent negative T wave and stenosis greater than or equal to 65% (odds ratio 3.7, 3.7 and 3.3, respectively); 2) for angiographic restenosis were: presence of collateral vessels, ST segment depression, multivessel disease, left anterior descending coronary artery stenosis and history of recent onset of symptoms (odds ratio: 2.2, 2.0, 1.9, 1.9 and 0.54, respectively); and 3) for late coronary events (recurrence of angina, late myocardial infarction or late death) were: multivessel disease, total occluded vessel and ST segment elevation (odds ratio 3.7, 2.8 and 0.44, respectively). Thus, coronary angioplasty for unstable angina can be performed with a high initial success rate, but at an increased risk of major complications. The prognosis is favorable after initial successful coronary angioplasty

Nonlinear conductance reveals positions of carbon atoms in metallic single-wall carbon nanotubes

73.23.-b Electronic transport in mesoscopic systems, 73.63.Fg Nanotubes, 85.35.Ds Quantum interference devices,