Colonist, 1889-02-15

The Colonist began on 6 March 1886, changing its name to The Newfoundland Colonist after 18 July 1891. Having printed local and international news Monday to Saturday for six years, the paper came to an abrupt end when its offices were destroyed in The Great Fire of 8 July 1892.Title variations recorded in Alternative Title, as needed

The duration of pretreatment with ticlopidine prior to stenting is associated with the risk of procedure-related non–Q-wave myocardial infarctions

AbstractObjectives. This study sought to determine whether the duration of pretreatment with the adenosine diphosphate receptor antagonist ticlopidine prior to intracoronary stenting is associated with the incidence of procedure-related non–Q-wave myocardial infarctions (MIs).Background. Dual antiplatelet therapy with ticlopidine and aspirin is routinely used with stenting, although ticlopidine is commonly not begun until the day of the procedure. Periprocedural MIs are at least partially platelet-dependent events. As the maximal platelet inhibitory effects of this drug take 2 to 3 days to be realized, we hypothesized that longer treatment prior to stenting would be associated with lower rates of procedure-related MIs.Methods. We reviewed outcomes in 175 consecutive patients treated with ticlopidine prior to stenting at the Cleveland Clinic Foundation. Those patients with an elevation in creatine kinase above our laboratory normal (>210 IU/L) with ≥4% MB fraction on routine evaluation were defined as having a non–Q-wave MI.Results. There were 28 patients (16%) who had a non–Q-wave MI. Longer duration of ticlopidine pretreatment was strongly associated with a lower incidence of procedure-related non–Q-wave MIs (duration of pretreatment <1 day, 29% had MI; 1 to 2 days, 14%; ≥3 days, 5%; chi-square for trend = 9.6; p = 0.002). Ticlopidine pretreatment of ≥3 days was associated with a significant reduction in the risk of non–Q-wave MI (unadjusted odds ratio 0.18, 95% confidence interval = 0.04 to 0.78, p = 0.01) compared with pretreatment of <3 days.Conclusions. Among patients undergoing intracoronary stenting, beginning ticlopidine therapy several days prior to the procedure is associated with a reduced risk of procedural non–Q-wave MIs

Rapid platelet-function assay. An automated and quantitative cartridge-based method

Background-The platelet glycoprotein (GP) IIb/IIIa receptor is important in mediating platelet thrombus formation, and the GP IIb/IIIa antagonist abciximab (c7E3 Fab; ReoPro) is effective in preventing thrombotic ischemic cardiovascular complications of unstable angina and percutaneous coronary interventions. Small-molecule antagonists of GP IIb/IIIa based on the Arg-Gly-Asp (RGD) sequence show similar benefit, and some of these agents are orally active. However, there may be significant interindividual variation in response to such antagonists, especially with chronic oral therapy. It will be essential to balance the beneficial antithrombotic effect of these drugs with their potential for causing bleeding. In response to this need, we have developed a rapid platelet-function assay (RPFA), a point-of-care system that provides a quantitative measure of the competence of the GP IIb/IIIa receptor as reflected in the ability of platelets to agglutinate fibrinogen-coated beads. Methods and Results-Polystyrene beads were coated with fibrinogen and placed in a cartridge along with a lyophilized peptide that activates the thrombin receptor. Anticoagulated whole blood was added to the cartridge, and then a microprocessor-controlled operation mixed the reagents and detected agglutination between platelets and coated beads. Quantitative digital results were displayed within 3 minutes. Because there is no dilution of the blood, the assay can be used to measure platelet activity in samples that have been treated with GP IIb/IIIa antagonists with high dissociation rates. RPFA results of whole-blood samples treated with different GP IIb/IIIa antagonists correlated well with both conventional turbidimetric platelet aggregation (r 2 ϭ0.95) and the percentage of free GP IIb/IIIa molecules in the sample (r 2 ϭ0.96). The mean difference in measurements between RPFA and aggregometry was -4% (Ϯ4% SD), and the mean difference in measurements between RPFA and free GP IIb/IIIa receptors was -2% (Ϯ6% SD). Conclusions-Th

Delivering effective care through mobile apps:Findings from a multi-stakeholder design science approach

In this paper, we use a design science approach to develop a mobile app for lung cancer patients that facilitates their interactions with their clinicians, manages and reports on their health status, and provides them access to medical information/education. This paper contributes to the information systems literature by demonstrating the value of design science research to co-create solutions that advance health care outcomes through technological innovations. The design process engaged a diverse cast of experts and methods, such as a survey of oncologists and cancer patients, a workshop, roundtables and interviews with leading patient and clinician association representatives and focus groups, including two panels each of clinicians and cancer patients. Our approach also develops actionable knowledge that is grounded in evidence from the field, including design guidelines that recapitulate what we learned from the design-testing-redesign cycles of our artefact

Post-stroke inhibition of induced NADPH oxidase type 4 prevents oxidative stress and neurodegeneration

Ischemic stroke is the second leading cause of death worldwide. Only one moderately effective therapy exists, albeit with contraindications that exclude 90% of the patients. This medical need contrasts with a high failure rate of more than 1,000 pre-clinical drug candidates for stroke therapies. Thus, there is a need for translatable mechanisms of neuroprotection and more rigid thresholds of relevance in pre-clinical stroke models. One such candidate mechanism is oxidative stress. However, antioxidant approaches have failed in clinical trials, and the significant sources of oxidative stress in stroke are unknown. We here identify NADPH oxidase type 4 (NOX4) as a major source of oxidative stress and an effective therapeutic target in acute stroke. Upon ischemia, NOX4 was induced in human and mouse brain. Mice deficient in NOX4 (Nox4(-/-)) of either sex, but not those deficient for NOX1 or NOX2, were largely protected from oxidative stress, blood-brain-barrier leakage, and neuronal apoptosis, after both transient and permanent cerebral ischemia. This effect was independent of age, as elderly mice were equally protected. Restoration of oxidative stress reversed the stroke-protective phenotype in Nox4(-/-) mice. Application of the only validated low-molecular-weight pharmacological NADPH oxidase inhibitor, VAS2870, several hours after ischemia was as protective as deleting NOX4. The extent of neuroprotection was exceptional, resulting in significantly improved long-term neurological functions and reduced mortality. NOX4 therefore represents a major source of oxidative stress and novel class of drug target for stroke therapy

Is platelet inhibition due to thienopyridines increased in elderly patients, in patients with previous stroke and patients with low body weight as a possible explanation of an increased bleeding risk?

Background The TRITON-TIMI 38 study has identified three subgroups of patients with a higher risk of bleeding during treatment with the thienopyridine prasugrel: patients with a history of stroke or transient ischaemic attack (TIA), patients ≥75 years and patients with a body weight <60 kg. However, the underlying pathobiology leading to this increased bleeding risk remains to be elucidated. The higher bleeding rate may be due to a stronger prasugrelinduced inhibition of platelet aggregation in these subgroups. The aim of the present study was to determine whether on-treatment platelet reactivity is lower in these risk subgroups as compared with other patients in a large cohort on the thienopyridine clopidogrel undergoing elective coronary stenting. Methods A total of 1069 consecutive patients were enrolled. On-clopidogrel platelet reactivity was measured in parallel by light transmittance aggregometry, the Verify- Now®P2Y12 assay and the PFA-100 collagen/ADP cartridge. Results Fourteen patients (1.5%) had a prior history of stroke or TIA, 138 patients (14.5%) were older than 75 years and 30 patients (3.2%) had a body weight <60 kg. Age ≥75 years and a history of stroke were independent predictors of a higher on-treatment platelet reactivity. In contrast, a body weight <60 kg was significantly associated with a lower on-treatment platelet reactivity. Conclusion In two high-risk subgroups for bleeding, patients ≥75 years and patients with previous stroke, onclopidogrel platelet reactivity is increased. In contrast, in patients with a low body weight, on-clopidogrel platelet reactivity is decreased, suggesting that a stronger response to a thienopyridine might only lead to more bleeds in patients with low body weight

'Aspirin resistance' or treatment non-compliance: Which is to blame for cardiovascular complications?

Aspirin is one of the 'cornerstone' drugs in our current management of cardiovascular disorders. However, despite the prescription of aspirin recurrent vascular events still occur in 10–20% of patients. These, data together with the observations of diminished antiaggregatory response to aspirin in some subjects have provided the basis of the current debate on the existence of so-called "aspirin resistance". Unfortunately, many of the tests employed to define 'aspirin resistance' lack sufficient sensitivity, specificity, and reproducibility. The prevalence of 'aspirin resistance' as defined by each test varies widely, and furthermore, the value of a single point estimate measure of aspirin resistance is questionable. The rate of 'aspirin resistance' is law if patients observed to ingest aspirin, with large proportion of patients to be pseudo-'aspirin resistant', due to non-compliance. What are the implications for clinical practice? Possible non-adherence to aspirin prescription should also be carefully considered before changing to higher aspirin doses, other antiplatelet drugs (e.g. clopidogrel) or even combination antiplatelet drug therapy. Given the multifactorial nature of atherothrombotic disease, it is not surprising that only about 25% of all cardiovascular complications can usually be prevented by any single medication. We would advocate against routine testing of platelet sensitivity to aspirin (as an attempt to look for 'aspirin resistance') but rather, to highlight the importance of clinicians and public attention to the problem of treatment non-compliance

Duration of clopidogrel treatment and risk of mortality and recurrent myocardial infarction among 11 680 patients with myocardial infarction treated with percutaneous coronary intervention: a cohort study

<p>Abstract</p> <p>Background</p> <p>The optimal duration of clopidogrel treatment after percutaneous coronary intervention (PCI) is unclear. We studied the risk of death or recurrent myocardial infarction (MI) in relation to 6- and 12-months clopidogrel treatment among MI patients treated with PCI.</p> <p>Methods</p> <p>Using nationwide registers of hospitalizations and drug dispensing from pharmacies we identified 11 680 patients admitted with MI, treated with PCI and clopidogrel. Clopidogrel treatment was categorized in a 6-months and a 12-months regimen. Rates of death, recurrent MI or a combination of both were analyzed by the Kaplan Meier method and Cox proportional hazards models. Bleedings were compared between treatment regimens.</p> <p>Results</p> <p>The Kaplan Meier analysis indicated no benefit of the 12-months regimen compared with the 6-months in all endpoints. The Cox proportional hazards analysis confirmed these findings with hazard ratios for the 12-months regimen (the 6-months regimen used as reference) for the composite endpoint of 1.01 (confidence intervals 0.81-1.26) and 1.24 (confidence intervals 0.95-1.62) for Day 0-179 and Day 180-540 after discharge. Bleedings occurred in 3.5% and 4.1% of the patients in the 6-months and 12-months regimen (p = 0.06).</p> <p>Conclusions</p> <p>We found comparable rates of death and recurrent MI in patients treated with 6- and 12-months' clopidogrel. The potential benefit of prolonged clopidogrel treatment in a real-life setting remains uncertain.</p

Clinical outcomes according to permanent discontinuation of clopidogrel or placebo in the CHARISMA trial

SummaryBackgroundLate discontinuation of clopidogrel after an acute coronary syndrome or stent placement may be associated with a clinical rebound effect.AimsTo describe the characteristics and evolution of patients non-compliant to study drug in the prospective, randomized, double-blind CHARISMA trial.MethodsOf 15,603 patients aged 45 or older years with established atherothrombotic disease (coronary artery disease, stroke, peripheral arterial disease) or multiple cardiovascular risk factors, 2999 permanently interrupted (withdrawers) study drug (clopidogrel or placebo) during follow-up. The primary endpoint was first occurrence since randomization of myocardial infarction, stroke or cardiovascular death.ResultsWithdrawers displayed a higher risk profile and rates of death/myocardial infarction/stroke (13.5% versus 5.6%; hazard ratio [HR]: 3.18; 95% confidence interval [CI]: 3.05–3.32; p<0.001) and severe bleeding (4.9% versus 0.7%; odds ratio [OR]: 7.42; 95% CI: 5.67–9.70; p<0.001) versus non-withdrawers. Death/myocardial infarction/stroke occurred after an average of 228 days (95% CI: 197–258) and was less frequent in patients assigned to clopidogrel versus placebo (9.7% versus 11.9%; HR: 0.80; 95% CI: 0.64–1.00; p=0.051); the rate of severe bleeding was the same (4.0% versus 4.3%; OR: 0.92; 95% CI: 0.65–1.32; p=0.66). Among withdrawers, initial clopidogrel treatment was an independent correlate of survival (HR: 0.74, 95% CI: 0.59–0.93; p=0.011), but not severe bleeding (OR: 0.94; 95% CI: 0.65–1.35; p=0.74). Kaplan-Meier curves for the primary endpoint suggested no rebound effect or disease reactivation after discontinuation of clopidogrel compared with placebo.ConclusionsPatients who stopped medication had increased rates of ischaemic and bleeding events and mortality. Patients initially on clopidogrel had fewer ischaemic events than those on placebo; discontinuation was not associated with any clinically detectable rebound effect