Background and Purpose-The widespread use of aspirin requires clarification of the aspirin resistance phenomenon.Most studies on this field are focused on patients which may affect the action of aspirin. Methods-We evaluated the biological efficacy of aspirin in healthy subjects. Results-Agonist-induced platelet aggregation was fully abrogated by 100 mg of aspirin in all individuals. By contrast, with the platelet function analyzer-100 device, 33.3% of the subjects displayed no response. This failure was overcome by 500 mg or by in vitro treatment of blood with 30 mol/L acetylsalicylic acid. Intake of 100 mg of aspirin efficiently reduced by 75% the level of 11-dehydro thromboxane B 2 (11-dTxB 2 ) in all cases. However, variability on the pre-aspirin level (range 72.4 to 625.9 ng/mmol creatinine) led to substantial differences in the residual amount of the metabolite between subjects treated with aspirin (range 12.9 to 118.0 ng/mmol creatinine). Finally, there was no influence of platelet glycoprotein IIb/IIIa (Pro33Leu), platelet glycoprotein Ia/IIa, (C807T), and FXIII (Val34Leu) polymorphisms on the efficacy of aspirin. However, the cyclooxygenase (Cox)-1 50T allele associated with higher level of 11-dTxB 2 , both before and after aspirin. Moreover, the Cox-2 Ϫ765C variant displayed a slightly higher reduction in 11-dTxB 2 level on treatment with aspirin. Conclusions-Our findings suggest that full resistance of healthy subjects to aspirin is rather unlikely. However, differences in aspirin absorption, or pharmacokinetic, or other unrecognized factors may lead to lack of effect of low dose of aspirin in some subjects when using tests like platelet function analyzer-100. Whether Cox polymorphisms are thrombotic risk factor for patients under aspirin will require further research.

IntroductionThis study is an analysis of a pilot COPD clinical audit that evaluated adherence to guidelines for patients with COPD in a stable disease phase during a routine visit in specialized secondary care outpatient clinics in order to identify the variables associated with the decision to step-up or step-down pharmacological treatment.MethodsThis study was a pilot clinical audit performed at hospital outpatient respiratory clinics in the region of Andalusia, Spain (eight provinces with over eight million inhabitants), in which 20% of centers in the area (catchment population 3,143,086 inhabitants) were invited to participate. Treatment changes were evaluated in terms of the number of prescribed medications and were classified as step-up, step-down, or no change. Three backward stepwise binominal multivariate logistic regression analyses were conducted to evaluate variables associated with stepping up, stepping down, and inhaled corticosteroids discontinuation.ResultsThe present analysis evaluated 565 clinical records (91%) of the complete audit. Of those records, 366 (64.8%) cases saw no change in pharmacological treatment, while 99 patients (17.5%) had an increase in the number of drugs, 55 (9.7%) had a decrease in the number of drugs, and 45 (8.0%) noted a change to other medication for a similar therapeutic scheme. Exacerbations were the main factor in stepping up treatment, as were the symptoms themselves. In contrast, rather than symptoms, doctors used forced expiratory volume in 1 second and previous treatment with long-term antibiotics or inhaled corticosteroids as the key determinants to stepping down treatment.ConclusionThe majority of doctors did not change the prescription. When changes were made, a number of related factors were noted. Future trials must evaluate whether these therapeutic changes impact clinically relevant outcomes at follow-up.

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Combinations of beta-lactamase inhibitors with penicillins, especially aminopenicillins, have broad-spectrum antibacterial activity against most of the common pathogens of the respiratory and urinary tracts. This means that they are an ideal treatment for infections such as otitis media, sinusitis, special cases of pharyngeal tonsillitis (recurring forms, indirect pathogenic action, or after the failure of amoxicillin monotherapy), acute exacerbations of chronic bronchitis, cystitis, urethritis, etc. The amoxicillin-sulbactam combination is active against both beta-lactamase producer and nonproducer strains, and is effective against Gram-positive cocci (Streptococcus pneumoniae, Streptococcus pyogenes, Staphylococcus aureus of nonhospital origin), Gram-negative cocci (Neisseria gonorrhoeae, Moraxella catarrhalis and others), Gram-negative bacilli (nonhospital strains of Haemophilus influenzae, Escherichia coli and Klebsiella pneumoniae and others) and anaerobes. Its antimicrobial activity means that it is indicated in the treatment of respiratory, ear, nose and throat, urinary, dermatological and gynecological infections caused by susceptible germs, as well as in a variety of surgical situations (both as a treatment and as prophylaxis). It is absorbed very well orally, and its pharmacokinetic profile is very favorable, with very good tissue penetration. It is reasonably well tolerated: in a variable percentage of cases it may cause modification of intestinal transit and/or fecal consistency, which usually abates spontaneously. The new formulation for administration at intervals of 12 h is easier to use, is better tolerated and favors completion of therapy. In summary, the amoxicillin-sulbactam combination is effective and well tolerated in most infections of nonhospital origin in adults and children. (c) 2001 Prous Science. All rights reserved.