Coumarin anticoagulants and co-trimoxazole: avoid the combination rather than manage the interaction

OBJECTIVE: The objective of our study was to examine the management of the interaction between acenocoumarol or phenprocoumon and several antibiotics by anticoagulation clinics and to compare the consequences of this interaction on users of co-trimoxazole with those for users of other antibiotics. METHODS: A follow-up study was conducted at four anticoagulation clinics in The Netherlands. Data on measurements of the International Normalised Ratio (INR), application of a preventive dose reduction (PDR) of the coumarin anticoagulant, fever and time within or outside the therapeutic INR range were collected. RESULTS: The study cohort consisted of 326 subjects. A PDR was given more often to users of co-trimoxazole PDR than to users of other antibiotics. The PDR in co-trimoxazole users resulted in a significantly reduced risk of both moderate overanticoagulation (INR >4.5) and severe overanticoagulation (INR >6.0) compared with no PDR, with odds ratios (ORs) of 0.06 [95% confidence interval (CI): 0.01-0.51] and 0.09 (95% CI: 0.01-0.92), respectively. In co-trimoxazole users without PDR, the risk of overanticoagulation was significantly increased compared with users of other antibiotics. All co-trimoxazole users spent significantly more time under the therapeutic INR range during the first 6 weeks after the course than users of other antibiotics. CONCLUSION: PDR is effective in preventing overanticoagulation in co-trimoxazole users, but results in a significantly prolonged period of underanticoagulation after the course. Avoidance of concomitant use of co-trimoxazole with acenocoumarol or phenprocoumon seems to be a safer approach than management of the interaction between these drugs

The Pioneer Anomaly

Radio-metric Doppler tracking data received from the Pioneer 10 and 11 spacecraft from heliocentric distances of 20-70 AU has consistently indicated the presence of a small, anomalous, blue-shifted frequency drift uniformly changing with a rate of ~6 x 10^{-9} Hz/s. Ultimately, the drift was interpreted as a constant sunward deceleration of each particular spacecraft at the level of a_P = (8.74 +/- 1.33) x 10^{-10} m/s^2. This apparent violation of the Newton's gravitational inverse-square law has become known as the Pioneer anomaly; the nature of this anomaly remains unexplained. In this review, we summarize the current knowledge of the physical properties of the anomaly and the conditions that led to its detection and characterization. We review various mechanisms proposed to explain the anomaly and discuss the current state of efforts to determine its nature. A comprehensive new investigation of the anomalous behavior of the two Pioneers has begun recently. The new efforts rely on the much-extended set of radio-metric Doppler data for both spacecraft in conjunction with the newly available complete record of their telemetry files and a large archive of original project documentation. As the new study is yet to report its findings, this review provides the necessary background for the new results to appear in the near future. In particular, we provide a significant amount of information on the design, operations and behavior of the two Pioneers during their entire missions, including descriptions of various data formats and techniques used for their navigation and radio-science data analysis. As most of this information was recovered relatively recently, it was not used in the previous studies of the Pioneer anomaly, but it is critical for the new investigation.Comment: 165 pages, 40 figures, 16 tables; accepted for publication in Living Reviews in Relativit

The pharmacists' potential to provide targets for interventions to optimize pharmacotherapy in patients with asthma

<p>Background Despite of pharmacists' specialized knowledge of medication and his/her regular contact with patients, the expertise of the pharmacist may not be used enough yet. Furthermore, the potential of pharmacy dispensing data is underestimated. Objective To provide targets for tailored interventions in asthma patients and to illustrate the potential value of pharmacists in the identification of these targets using individual pharmacy dispensing data. Setting We performed a cross sectional retrospective analysis assessing the quality of asthma patients' pharmacotherapeutic treatment. Method Drug dispensing data from 2008 to 2009 were retrieved from a Dutch pharmacy database. All asthma patients were screened for potential suboptimal pharmacotherapy in 2009. Results were projected to a single community pharmacy to provide an estimate of the number of patients eligible for potential interventions. Main outcome measures (1) frequent use of short-acting beta-agonists without preventive medication, (2) concomitant use of beta-blockers, (3) multiple short courses of oral corticosteroids without using inhaled corticosteroids and 4) use of long-acting beta-agonist without inhaled corticosteroids. Results A total of 8,504 patients were eligible for analysis of the quality of their asthma treatment. 20.9 % of all asthma patients used > 100 DDD short-acting beta-agonists per year, whereas between 21.2 % (a parts per thousand yen400 DDD) and 31.4 % (100-199 DDD) of these patients did not receive preventive medication. Approximately 5.2 % of the asthma patients are using beta-blockers concomitantly and 21.8 % of them received non-cardioselective beta-blockers. 6.3 % of the asthma patients received two or more oral courses of corticosteroids in 2008 and 17.4 % of these patients did not receive inhaled corticosteroids in 2009. 2.9 % of the patients used a long-acting beta-agonists without inhaled corticosteroids. 8.4 % of the asthma patients using both long-acting beta-agonists and inhaled corticosteroids received these drugs in two separate inhalers. We estimated that about 400 asthma patients could be identified in an average pharmacy population (8,000 patients) and 33 (95 % CI 22-44) of these patients would be eligible for interventions. Conclusion This study shows the potential for pharmacists to use their own pharmacy records to identify suboptimal therapy of asthma patients, who may be targets for tailored interventions.</p>