[Which place for direct oral anticoagulants in routine hospital medical practice?]. / Quelle place pour les anticoagulants oraux directs en pratique hospitalière quotidienne?

PURPOSE: More than one million patients received an oral anticoagulant treatment in France. This medication is the first aetiology of iatrogenic events. Recently, direct oral anticoagulant (DOA) provided efficacy and safety in the treatment of atrial fibrillation and venous thromboembolic events. Given the growing increase in the prescription of these molecules, with many advantages but also disadvantages, it seemed interesting to assess in routine hospital medical practice, the proportion of patients for which the initiation of AOD could be safe. METHODS: This prospective, observational study was conducted in the department of internal medicine from October 2012 and September 2013. All inpatients receiving oral anticoagulant treatment have been included. Demographic data, indication of anticoagulant treatment, contraindications and interactions have been reported. From these information, we have established the percentage of patients who could benefit from DOA safely and securely. RESULTS: Two hundred and ninety inpatients were included with a mean age of 76.3±15.2 years old. Atrial fibrillation and thromboembolic venous disease were the most prevalent indications of anticoagulant treatments (67.2% and 22.4% of cases respectively). Among all patients, 260 had an indication of DOA (89.7%), authorized by the French National health agency. Eighty percent had both indication and no contraindication for DOA. However, only 53.1% of patients neither had drug-drug interaction. Main contraindications were severe renal failure (clearance<30mL/min) in 10.7% of cases, and recent history of gastric ulcer in 15.3% of cases. The most frequent interactions with DOA were antiplatelet agent (14.5%) and amiodarone (11.6%). Almost two thirds of inpatients (65.1%) had at least one drug-drug interaction with VKA. CONCLUSION: These results, coming from "real life", provide that only 53.1% of inpatients under anticoagulants could receive DOA safely. Caution is warranted, and VKA still have a preponderant role among anticoagulant drugs.

[Crushing drugs in geriatric units: an "handicraft" practice with frequent errors which imposed recommendations]. / L'écrasement des médicaments en gériatrie: une pratique « artisanale ¼ avec de fréquentes erreurs qui nécessitait des recommandations.

PURPOSE: Swallowing disorders or psycho-behavioural distress frequently interfere on drug administration in elderly inpatients. Crushing drugs is a common although non validated practice. The objective of this first prospective study, performed in all geriatric units of the Rouen university hospital by a multidisciplinary group, was to assess the crushing practice, from the prescription to the administration of the drugs in order to elaborate corrective measures. METHODS: A survey was performed in June 2009 and included 683 inpatients, 65 years and above, in 23 geriatric units. If a patient received drugs after crushing, we recorded the reason for crushing, what drugs were crushed, the galenic presentations and the technique used for preparation and administration. RESULTS: Two hundred and twenty-one patients (32.3%) (85.5 ± 6.5 years, females 74.2%) received 1528 drugs (6.9 ± 4 per patient) including 966 drugs (63.2%) after crushing (crushed pills or crushed content of opened capsules), mainly in the morning (50.4%). The main reasons for crushing drugs were swallowing disorders and psycho-behavioural distress. Forty-two percent of crushed drugs had a galenic presentation which did not allow crushing. The patient's drugs were crushed together three out of four times and mixed with different vehicules for administration. The material used for crushing (a mortar, 92.6%) was often the same for several patients (59.4%); 83.5% of crushed drugs were immediately administered to the patients, though there were important variations about schedules of administration. CONCLUSION: Crushing drugs expose both to iatrogenic hazards and professional risks. Regional and national recommendations were developed in order to correct the errors linked to this practice.

Risk factors of vitamin K antagonist overcoagulation.

OBJECTIVES: The aims of this prospective study were to identify, in vitamin K antagonist (VKA)-treated patients, factors associated with INR values: (i) greater than 6.0. and (ii) ranging from 4.0 to 6.0 complicated with bleeding. We also assessed VKA-related morbidity in these patients. METHODS: During a 6-month period, 3090 consecutive patients were referred to our Department of Internal Medicine, including 412 VKA-treated patients. At admission, the medical records of VKA-treated patients were reviewed for type, duration and indication of VKA therapy, previous medical history of VKA-related hemorrhage, comorbidities and concomitant medications. RESULTS: Forty of the 412 VKA-treated patients (9.7%) exhibited oral anticoagulant related overcoagulation. VKA overcoagulation was associated with high morbidity, leading to major bleeding in 27.5% of cases; moreover, 12.5% of these patients died, death being mainly due to major bleeding. Under multivariate analysis, significant factors for VKA-related overcoagulation were as follows: previous medical history of VKA therapy-related hemorrhage (P=0.00001) and INR levels over therapeutic range (P=0.0006), chronic liver disease (P=0.03), therapy with amiodarone (P=0.009); in contrast, statin therapy was found to be a protective factor of VKA overcoagulation (P=0.008). CONCLUSIONS: The knowledge of predictive factors of VKA-related overcoagulation seems of utmost importance to improve patients' management. Our study underlines the fact that the potential of drug interaction should be taken into account when choosing amiodarone for patients receiving VKAs. Interestingly, long-term (>6 month) statin therapy may be a protective factor of VKA overcoagulation. Our findings, therefore, suggest that there may be no need to switch long-term users of VKA and statin to a safer alternative therapy.

[Evaluation of in-hospital prescription of fluoroquinolones]. / Evaluation des pratiques de prescription des fluoroquinolones à l'hôpital.

PURPOSE: Quinolones are widely prescribed in various hospital departments (about 20% of antibiotics prescriptions in some of them) and antibiotic resistances is increasingly documented. The aim of this prospective study was to assess the prescriptions of quinolones in several departments of medicine of Rouen University Hospital and compare them to the guidelines of good medical practice for antibiotic prescriptions. METHODS: This study was performed in four medicine departments during two months. When a physician prescribed a quinolone treatment, he had to record informations regarding the infection (type and site, bacteriological proof or not), the patient (age, sex and glomerular filtration rate) and the prescription of quinolone (indication, dosage, administration, combination with another antibiotic, duration of treatment). RESULTS: A hundred and three prescriptions of quinolones were analysed (mean age 75+/-0.5 years). Quinolones treatments were more often used alone, in first intention and without bacteriological proof. The dosage of quinolones was generally adapted but the duration of treatment was often excessive. Quinolones prescriptions were in majority in accordance with the guidelines for pulmonary infections, but were more often inappropriate for urinary infections. CONCLUSION: According to the infections, this study shows discrepancies with the published guidelines with respect to prescription of quinolones, but there are also differences between available guidelines that may at least in part explain our results. An harmonization and a large diffusion of uniform guidelines could improve patients antibiotherapy.

Determination of pyrazinamide and its main metabolites in rat urine by high-performance liquid chromatography.

A new high-performance liquid chromatograhic procedure for simultaneous determination of pyrazinamide (PZA) and its three metabolites 5-hydroxypyrazinamide (5-OH-PZA), pyrazinoic acid (PA), and 5-hydroxypyrazinoic acid (5-OH-PA), in rat urine was developed. 5-OH-PZA and 5-OH-PA standards were obtained by enzymatic synthesis (xanthine oxidase) and checked by HPLC and GC-MS. Chromatographic separation was achieved in 0.01 M KH2PO4 (pH 5.2), circulating at 0.9 ml/min, on a C18 silica column, at 22 degrees C. The limits of detection were 300 microg/l for PZA, 125 microg/l for PA, 90 microg/l for 5-OH-PZA and 70 microg/l for 5-OH-PA. Good linearity (r2>0.99) was observed within the calibration ranges studied: 0.375-7.50 mg/l for PZA, 0.416-3.33 mg/l for PA, 0.830-6.64 mg/l for 5-OH-PZA and 2.83-22.6 mg/l for 5-OHPA. Accuracy was always lower than +/- 10.8%. Precision was in the range 0.33-5.7%. The method will constitute a useful tool for studies on the influence of drug interactions in tuberculosis treatment.