Impact of recommendations on crushing medications in geriatrics: from prescription to administration.

The practice of crushing drugs is very common in geriatric units. In 2009 a first study, performed in all geriatric units of a university hospital, showed that numerous errors were made during prescription, preparation and administration. The aim of this second prospective study was to assess the impact of regional and national recommendations in the same geriatric units. A survey of 719 patients (85.3 ± 6.7 years) was performed in 2013. For each patient who received crushed drugs, we recorded the reason the drugs were crushed, pharmacological classes, galenic presentations and the technique used for preparation and administration. Results were compared to the previous study. The number of patients receiving drugs after crushing was significantly lower than in the previous study (22.9% vs. 32.3%, P < 0.001). The number of crushed drugs was lower too (594 per 165 patients vs. 966 per 224 patients (P < 0.01). The main indication for crushing drugs remained swallowing disorders. The dosage form prevented crushing in 24.9% of drugs (vs. 42.0% in 2009, P < 0.001), but the drugs generally remained crushed all together. A mortar was used less often (38.6% vs. 92.6%, P < 0.001), with preference for individual-specific cups (56.1%). Mortars were more often cleaned between each patient (56.0% vs. 11.6%). The vehicle was more often neutral (water 88.5% vs. 5.7%, P < 0.001). This second study shows that regional and national recommendations have led to an overall improvement of practices for crushing drugs. Technical improvements are still possible, in association with appropriate pharmacological studies.

Antiplatelet drugs in the elderly: prescriptions often inappropriate and reduced tolerance by associated diseases and drugs.

To assess the conditions of prescriptions and tolerance of antiplatelet drugs (APD) in the elderly and to detail the parameters that influence the tolerance of these drugs. Prospective survey in a Department of Geriatric Medicine. Two hundred nineteen patients 70 years and older treated with one or two APD prior to admission were included during 7 months in 2008. We recorded the type of APD, associated diseases, main associated or co-prescribed drugs which could interact with APD and the bleeding adverse events including cutaneous bleeding. The mean age of the 219 patients was 84.5 ± 6.7 years (70-101 years), women 59.4%. Among patients 64.8% received aspirin (mainly 75 mg), 28.3% received clopidogrel and 6.8% received their combination; 16.9% of prescriptions were off-label; 51.6% of patients had an associated disease and/or an associated drug which could have increased risk of bleeding event. Among the patients who received a gastric-protective drug, the prescription followed the recommendations of the French Health Authority in 38.9%. We recorded bleeding events in 24.2% of patients at admission and in 18.3% of patients during the hospitalization. Bleeding events were significantly more frequent in patients treated with aspirin than clopidogrel (40.8 vs. 24.2%, P < 0.05) and/or with an associated drug (OR = 2.36, 95% CI 1.34-4.14, P < 0.01) and/or an associated disease (OR = 1.22, 95% CI 1.01-3.42, P < 0.05). APD treatment was stopped in 28.8% of patients, mainly because lack of indication or bleeding adverse events. Off-label prescriptions of APD were not rare in the elderly, and adverse events are frequent. The results of this preliminary study evoke that medical situations at increased risk of bleeding are perhaps insufficiently evaluated, either in case of prescription of associated drugs with increased bleeding risk or during the follow-up of patients with associated diseases. Cutaneous bleeding events should be more taken into account in prospective studies.

Improvement of peripheral endothelial dysfunction by protein tyrosine phosphatase inhibitors in heart failure.

BACKGROUND: Chronic heart failure (CHF) induces endothelial dysfunction characterized by a decrease in nitric oxide (NO) production in response to flow (flow-mediated dilatation [FMD]). Because activation of endothelial NO synthase (eNOS) by flow requires tyrosine phosphorylation, we tested whether endothelial dysfunction could be corrected by increasing phosphotyrosine levels using protein tyrosine phosphatase (PTP) inhibitors and especially inhibitors of PTP1B. METHODS AND RESULTS: CHF was induced by coronary ligation in mice, and FMD was assessed in isolated and cannulated mesenteric artery segments (2 mm in length and <300 microm in diameter). CHF almost abolished FMD but only moderately affected the response to acetylcholine. In mice with CHF, the PTP1B inhibitors AS279, AS098, and AS713 restored FMD to levels similar to those of normal mice. This restoration was reduced by inhibitors of eNOS and phosphatidylinositol-3 kinase. Polymerase chain reaction and Western blot showed that arteries express PTP1B, and this expression was not affected by CHF. Immunolocalization revealed the presence of PTP1B in the endothelium and the adventitia. Flow induced a transient eNOS phosphorylation that was absent in CHF. PTP1B inhibition stimulated early eNOS phosphorylation and increased phosphorylation of Akt. CONCLUSIONS: Our results demonstrate for the first time that PTP1B inhibitors may be potent treatments for endothelial dysfunction.

[Are the prescriptions of anticholinesterasic drugs adapted to the associated diseases and/or drugs in the Alzheimer's dementia?]. / Les prescriptions de médicaments anticholinestérasiques sont-elles adaptées au contexte médical au cours de la démence de type Alzheimer?

The aim of this study was to evaluate if the prescriptions of anticholinesterase drugs took into account some diseases and drugs which could interfere with them, in 58 inpatients (82 years old). The anticholinesterase drugs were respectively at admission and discharge: donepezil (n = 27 and 34), galantamine (n = 12 and 19) and rivastigmine (n = 3 and 1). Nineteen patients received a combination of anticholinesterase drug with an anticholinergic drug (muscarinic antipsychotic 15 times). Twelve patients had a medical history which interfered with the anticholinesterase drug: uretroprostatic obstacle, chronic renal failure and auriculo-ventricular block. Thirty-five adverse drug reactions, mainly in digestive track, were recorded in 26 patients. The treatment with anticholinesterase drug was modified only in 18 patients and the combination of anticholinesterase drug and antipsychotic agent was stopped in 5 patients. In conclusion, inappropriated prescriptions of anticholinesterase drugs seem frequent, with a more important prevalence of adverse drug reactions than in prospective studies. These results incite to develop studies of evaluation of prescriptions of anticholinesterase drugs.