Prescriptions for selective cyclooxygenase-2 inhibitors, non-selective non-steroidal anti-inflammatory drugs, and risk of breast cancer in a population-based case-control study

INTRODUCTION. Non-steroidal anti-inflammatory drugs (NSAIDs) prevent the growth of mammary tumours in animal models. Two population-based case-control studies suggest a reduced risk of breast cancer associated with selective cyclooxygenase-2 (sCox-2) inhibitor use, but data regarding the association between breast cancer occurrence and use of non-selective NSAIDs are conflicting. METHODS. We conducted a population-based case-control study using Danish healthcare databases to examine if use of NSAIDs, including sCox-2 inhibitors, was associated with a reduced risk of breast cancer. We included 8,195 incident breast cancer cases diagnosed in 1991 through 2006 and 81,950 population controls. RESULTS. Overall, we found no reduced breast cancer risk in ever users (>2 prescriptions) of sCox-2 inhibitors (odds ratio (OR) = 1.08, 95% confidence interval (95% CI) = 0.99, 1.18), aspirin (OR = 0.98, 95% CI = 0.90-1.07), or non-selective NSAIDs OR = 1.04, (95% CI = 0.98, 1.10)). Recent use (>2 prescriptions within two years of index date) of sCox-2 inhibitors, aspirin, or non-selective NSAIDs was likewise not associated with breast cancer risk (Ors = 1.06 (95% CI = 0.96, 1.18), 0.96 (95% CI = 0.87, 1.06) and 0.99 (95% CI = 0.85, 1.16), respectively). Risk estimates by duration (<10, 10 to 15, 15+ years) or intensity (low/medium/high) of NSAID use were also close to unity. Regardless of intensity, shorter or long-term NSAID use was not significantly associated with breast cancer risk. CONCLUSIONS. Overall, we found no compelling evidence of a reduced risk of breast cancer associated with use of sCox-2 inhibitors, aspirin, or non-selective NSAIDs.Karen Elise Jensen Foundatio

Increased αCGRP potency and CGRP-receptor antagonist affinity in isolated hypoxic porcine intramyocardial arteries

1. This study describes the effects of hypoxia on relaxing responses and cAMP production induced by the known vasodilator peptides: αCGRP, amylin (AMY) and adrenomedullin (AM) on isolated pig coronary arteries in vitro. 2. Hypoxic incubation increased the vasorelaxant effect of αCGRP (four-fold; P<0.05), AMY (3.2-fold; P<0.05), but not significantly for AM (two-fold; NS). 3. Whereas hypoxia had no effect on arterial cAMP levels, it significantly potentiated the production of cAMP stimulated of αCGRP and AMY, but not of AM. 4. The antagonist αCGRP(8–37) also exerted an increased effect in hypoxia. The Schild plot-derived pK(B) values revealed an increase in the apparent affinity of the antagonist for the CGRP(1) receptor from 7.0 to 7.2 under control conditions versus 8.0 in hypoxia. 5. Removal of endothelium, peptidase inhibitors, preincubation with the adenosine A(2A) receptor antagonist CSC (10(−3) M), the ATP-sensitive K-channel inhibitor glibenclamide (10(−5) M), the cyclooxygenase inhibitor indomethacin (10(−3) M) or NG-monomethyl-L-arginine (10(−4) M) had no effect on the αCGRP-induced vasorelaxation in hypoxia; neither did hypoxia influence the levels of CGRP and AM receptor mRNA. 6. We conclude that hypoxic incubation increases the relaxation and cAMP production induced by αCGRP and AMY in rings of porcine coronary arteries in vitro. A concomitant release of adenosine, a cyclooxygenase product, an endothelium-derived substance, activation of vascular ATP-sensitive K-channels, peptidase inhibitors or changes in CGRP and AM receptor mRNA cannot account for the changes observed in hypoxia. Moreover, αCGRP(8–37) showed increased affinity at the CGRP(1) receptor during hypoxia, possibly due to a conformational change at the CGRP(1) receptor site

2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European respiratory society (ERS) : The Task Force for the diagnosis and management of acute pulmonary embolism of the European Society of Cardiology (ESC)

Guidelines summarize and evaluate available evidence with the aim of assisting health professionals in proposing the best management strategies for an individual patient with a given condition. Guidelines and their recommendations should facilitate decision making of health professionals in their daily practice. However, the final decisions concerning an individual patient must be made by the responsible health professional(s) in consultation with the patient and caregiver as appropriate

2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS).

Guidelines summarize and evaluate available evidence with the aim of assisting health professionals in proposing the best management strategies for an individual patient with a given condition. Guidelines and their recommendations should facilitate decision making of health professionals in their daily practice. However, the final decisions concerning an individual patient must be made by the responsible health professional(s) in consultation with the patient and caregiver as appropriate

2019 ESC guidelines for the dignosis and management of acute pulmonary embolism developed in collaboration with the european respiratory society (ERS)

Guidelines summarize and evaluate available evidence with the aim of assisting health professionals in proposing the best management strategies for an individual patient with a given condition. Guidelines and their recommendations should facilitate decision making of health professionals in their daily practice. However, the final decisions concerning an individual patient must be made by the responsible health professional(s) in consultation with the patient and caregiver as appropriate