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- The Chemopreventive Efficacies of Nonsteroidal Anti-inflammatory Drugs: the Relationship of Short-term Biomarkers to Long-term Skin Tumor Outcome. [JOURNAL ARTICLE]
- Cancer Prev Res (Phila) 2013 May 16.
The UVB component of sunlight, which causes DNA damage and inflammation, is the major cause of nonmelanoma skin cancer (NMSC), the most prevalent of all cancers. Nonsteroidal anti-inflammatory drugs (NSAIDs) and coxibs have been shown to be effective chemoprevention agents in multiple preclinical trials, including NMSC, colon and urinary bladder cancer. NSAIDs, however, cause gastrointestinal irritation, which led to the recent development of nitric oxide (NO) derivatives that may partially ameliorate this toxicity. This study compared the efficacy of several NSAIDs and NO-NSAIDs on UV-induced NMSC in SKH-1 hairless mice and determined whether various short-term biomarkers were predictive of long-term tumor outcome with these agents. Naproxen at 100 (p>.05) and 400 ppm (p<.01) in the diet reduced tumor multiplicity by 26 and 63% respectively. The NO-naproxen at slightly lower molar doses shows similar activities. Aspirin at 60 or 750 ppm in the diet reduced tumor multiplicity by 19 and 50%; while the equivalent doses (108 and 1350 ppm) were slightly less effective. Sulindac at 25 and 150 ppm in the diet doses far below the Human Equivalent Dose, was the most potent NSAID with reductions of 50 and 94% respectively. In testing short-term biomarkers we found that agents that reduce UV-induced prostaglandin E2 synthesis and/or inhibit UV-induced keratinocyte proliferation yielded long-term tumor efficacy.
- Effect of Including Cancer Mortality on the Cost-Effectiveness of Aspirin for Primary Prevention in Men. [JOURNAL ARTICLE]
- J Gen Intern Med 2013 May 17.
BACKGROUND:Recent data suggest that aspirin may be effective for reducing cancer mortality.
OBJECTIVE:To examine whether including a cancer mortality-reducing effect influences which men would benefit from aspirin for primary prevention.
DESIGN:We modified our existing Markov model that examines the effects of aspirin among middle-aged men with no previous history of cardiovascular disease or diabetes. For our base case scenario of 45-year-old men, we examined costs and life-years for men taking aspirin for 10 years compared with men who were not taking aspirin over those 10 years; after 10 years, we equalized treatment and followed the cohort until death. We compared our results depending on whether or not we included a 22 % relative reduction in cancer mortality, based on a recent meta-analysis. We discounted costs and benefits at 3 % and employed a third party payer perspective. MAIN MEASURE: Cost per quality-adjusted life year (QALY) gained. KEY
RESULTS:When no effect on cancer mortality was included, aspirin had a cost per QALY gained of $22,492 at 5 % 10-year coronary heart disease (CHD) risk; at 2.5 % risk or below, no treatment was favored. When we included a reduction in cancer mortality, aspirin became cost-effective for men at 2.5 % risk as well (cost per QALY, $43,342). Results were somewhat sensitive to utility of taking aspirin daily; risk of death after myocardial infarction; and effects of aspirin on stroke, myocardial infarction, and sudden death. However, aspirin remained cost-saving or cost-effective (< $50,000 per QALY) in probabilistic analyses (59 % with no cancer effect included; 96 % with cancer effect) for men at 5 % risk.
CONCLUSIONS:Including an effect of aspirin on cancer mortality influences the threshold for prescribing aspirin for primary prevention in men. If such an effect is real, many middle-aged men at low cardiovascular risk would become candidates for regular aspirin use.
- Persistent antiphospholipid antibodies do not contribute to adverse pregnancy outcomes. [JOURNAL ARTICLE]
- Rheumatology (Oxford) 2013 May 16.
Objective.To determine whether women with persistent aPL (>12 weeks apart on at least two separate occasions) without a history of thrombosis or adverse pregnancy outcome had the same adverse pregnancy outcomes as those with obstetric APS or unmatched controls.Methods. This was a case-control study between 2005 and 2011 where we identified 73 women with persistent aPL and coincidentally the same number with obstetric APS. Unmatched controls were identified from low-risk clinics (ratio 1:4). Women with multiple pregnancies, fetal anomalies, SLE, thrombotic APS and other thrombophilias were excluded.
Results.Cases and controls were demographically similar, with the exception of younger controls with fewer medical comorbidities. aPL profiles were similar between aPL and APS. In women with aPL, risk of APS-type complications (odds ratio 1.3; 95% CI 0.6, 2.9) and birthweight distribution (median birthweight on a customized centile was 50.8, interquartile range 26.4-68.9; P < 0.05) were similar to controls. These findings persisted even after adjustment for maternal age and medical comorbidities.
Conclusion.Women with persistent aPL on aspirin had pregnancy outcomes that were similar to controls. These data suggest that in the absence of other risk factors, women with aPL do not need intense antenatal surveillance or modified management in pregnancy.
- Protection of vascular endothelium by aspirin in a murine model of chronic Chagas' disease. [JOURNAL ARTICLE]
- Parasitol Res 2013 May 17.
Chronic Chagas' disease affects 10-30 % of patients infected with Trypanosoma cruzi, and it mainly manifests as cardiomyopathy. Important pathophysiological mechanisms involved in the cardiac lesions include activation of the endothelium and induced microvascular alterations. These processes involve the production of endothelial adhesion molecules and thromboxane A2, which are involved in inflammatory cell recruitment and platelet aggregation, respectively. Cyclooxygenase inhibitors such as aspirin decrease thromboxane production and alter the course of Chagas' disease, both in the acute and chronic phases. We studied the effects of the administration of low and high doses of aspirin during the early phase of T. cruzi infection, following microvascular damage in the context of a chronic murine model of Chagas' disease. The effects of both schedules were assessed at 24 and 90 days postinfection by evaluating parasitemia, mortality, and cardiac histopathological changes as well as the expression of ICAM, VCAM, and E-selectin in cardiac tissue. Thromboxane A2, soluble ICAM, and E-selectin blood levels were also measured. While aspirin did not affect parasitemia or mortality in the infected mice, it decreased both cardiac inflammatory infiltrates and thromboxane levels. Additionally, at 90 days postinfection, aspirin normalized sICAM and sE-selectin levels. Considering the improved endothelial function induced by aspirin, we propose the possibility of including this drug in clinical therapy to treat chronic Chagas' disease.
- Antithrombotic Effects of Aspirin on One- or Two-Level Lumbar Spinal Fusion Surgery: A Comparison Between Two Groups Discontinuing Aspirin Use Before and After 7 Days Prior to Surgery. [JOURNAL ARTICLE]
- Spine (Phila Pa 1976) 2013 May 15.
Study Design. Retrospective clinical analysis
Objective.To study proper discontinuation date of aspirin in spinal fusion surgerySummary of Background Data. It is thought that excess bleeding can be normalized if aspirin intake is discontinued approximately 7 days before surgery; however, the average life span of a platelet is generally regarded to be 7 to 10 days.Methods. From January, 2004 to December, 2009, a single surgeon performed 182 cases of one- or two-level lumbar fusion surgeries. Patients who were aspirin users (n = 86) were divided into two groups according to the number of days prior to surgery that they discontinued their aspirin use: the Aspirin1 group discontinued their aspirin use 3 to 7 days before surgery and the Aspirin2 group discontinued their aspirin use 7 to 10 days before surgery. Ninety-six patients who did not use aspirin before surgery were selected for the control group. We retrospectively compared the several hematologic parameters among the two aspirin groups and the control group.
Results.Both the total amount of drained blood (DB) and the duration of indwelling of the drainage catheter (DD) were significantly less in the control group than in the Aspirin1 groups in patients that underwent either type of one-level fusion surgery. However, those were not significantly different between Aspirin 2 and control group in patients that underwent either type of one-level fusion surgery. Only DD was significantly less in the control group than in the Aspirin1 groups in patients that underwent two-level fusion surgery.
Conclusion.Only the Aspirin1 group, wherein patients discontinued aspirin use 3 to 7 days before surgery, showed a greater DB and DD than the control group. If aspirin was discontinued 7 days or longer before surgery, there was no difference in the study parameters, compared to the control group.
- Evaluation of the in vivo anti-inflammatory and analgesic and in vitro anti-cancer activities of curcumin and its derivatives. [Journal Article]
- Nat Prod Commun 2013 Mar; 8(3):359-62.
Curcumin, obtained from turmeric, has several biological properties to make it a desirable template for drug development. A lipophilic derivative of curcumin, diacetyl curcumin (DAC) and a hydrophilic derivative, diglutaryl curcumin (DGC) were synthesized and their in vivo analgesic and anti-inflammatory activities were compared with those of curcumin and aspirin. The in vitro anti-cancer activities of curcumin and the two derivatives against three cell cancer lines were compared with those against a non-cancerous cell line. The inhibitory effects were comparable to each other and nearing that of curcumin while they showed low inhibitory effect towards the non-cancerous cell line. The mouse tail flick assay showed that curcumin, DAC and DGC increased latency time. DGC was most effective as an analgesic, even more so than aspirin. The maximum percentage effect (MPE) was highest with DGC at 3 hours. The carrageenan induced paw edema model indicated anti-inflammatory activity of all three curcumin formulations. The percentage inhibition of paw edema was maximum for DAC, followed by aspirin and curcumin.
- Aspirin Half Maximal Inhibitory Concentration Value on Platelet Cyclooxygenase1 in Severe Type-2 Diabetes Mellitus is not Significantly Different from that of Healthy Individuals. [JOURNAL ARTICLE]
- Clin Appl Thromb Hemost 2013 May 14.
It is implicated that diabetic patients are more resistant to aspirin therapy than patients with other diseases or healthy individuals. We evaluated the inhibitory effects of aspirin on aggregation and the cyclooxygenase activity of platelets of 10 patients with severe type-2 diabetes mellitis (DM) and compared the results with those of healthy individuals. Although platelet aggregation had a tendency to be more resistant to aspirin with the DM group, there was no significant difference in half maximal inhibitory concentration 50 values of aspirin on the cyclooxygenase activity between the patients with DM and healthy individuals. Thus, the residual platelet aggregability uninhibited by aspirin appears to be independent of the cyclooxygenase activity. Since adenosine diphosphate (ADP) receptor blocking almost completely inhibited the residual platelet aggregability, it is suggested that hyperreactivity to ADP is more prevalent in patients with DM.
- Apixaban: A Review of its Use for Reducing the Risk of Stroke and Systemic Embolism in Patients with Nonvalvular Atrial Fibrillation. [JOURNAL ARTICLE]
- Drugs 2013 May 16.
The direct factor Xa inhibitor apixaban (Eliquis(®)) has predictable pharmacodynamics and pharmacokinetics and does not require routine anticoagulation monitoring. This article reviews the efficacy and tolerability of oral apixaban to reduce the risk of stroke or systemic embolism in patients with nonvalvular atrial fibrillation (AF). In the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial in patients with AF and at least one additional risk factor for stroke, apixaban recipients were significantly less likely than warfarin recipients to experience stroke or systemic embolism, major bleeding or death; the beneficial effects of treatment with apixaban versus warfarin were generally maintained across various patient subgroups. Apixaban recipients also had a significantly lower risk of intracranial haemorrhage than warfarin recipients. In the AVERROES (Apixaban Versus Acetylsalicylic Acid to Prevent Stroke in Atrial Fibrillation Patients who have Failed or are Unsuitable for Vitamin K Antagonist Therapy) trial in patients with AF and at least one additional risk factor for stroke for whom vitamin K antagonist therapy was unsuitable, apixaban was associated with a significantly lower risk of stroke or systemic embolism than aspirin, without an increase in the risk of major bleeding. In conclusion, although longer-term efficacy and safety data are needed, apixaban is an important new option for use in patients with nonvalvular AF to reduce the risk of stroke or systemic embolism.
This article describes the mechanism of action, pharmacokinetics, and pharmacodynamics of aspirin at doses used for cardiovascular prevention and provides specific management recommendations for optimal use in clinical practice. The paper highlights practical aspects related to antiplatelet therapy, including the optimal dose of aspirin, concomitant treatment with other NSAIDs, and strategies for the prevention of gastrointestinal toxicity. Specifically, we revise the benefits and hazards in different clinical settings to help the clinician in the decision-making process for individuals who have different risks for cardiovascular and gastrointestinal bleeding events.
- Association between non-steroidal anti-inflammatory drug use and melanoma risk: a meta-analysis of 13 studies. [JOURNAL ARTICLE]
- Cancer Causes Control 2013 May 16.