Identifying and preventing adverse drug events in elderly hospitalised patients: a randomised trial of a program to reduce adverse drug effects.

OBJECTIVES: Evaluate the impact of educational intervention in decreasing ADEs in elderly patients in a hospital setting. DESIGN: Randomised prospective study. SETTING: The study was performed in France in the Paris area, in 16 rehabilitation geriatric centres of APHP (Assistance Publique - Hôpitaux de Paris). Patient capacity per centre varied from 15 to 57 with a total of 526. PARTICIPANTS: All the patients > or = 65 years hospitalized during the 4 week study period were included. MEASUREMENTS: During a first 2 week phase without intervention ADE's were recorded in all centres. Then units were then randomised for an educational intervention or not. The educational phase lasted 1 week, without ADE tracking. Then, both types of units (I+ and I-) recorded ADEs for 2 weeks. Possible drug-related incidents were detected using a standardized check list (nurses) and a weekly review of all charts by investigators. Possible drug-related incidents were analysed by a group of reviewers selected from the authors to classify them as ADE or not. RESULTS: 576 patients (mean age: 83.6 +/- 7.9 years) were consecutively included. The mean number of drugs at inclusion was 9.4 +/- 4.24 drugs per patient. 223 out of 755 events were considered "probable" ADEs (29.5%). Among the 223 ADEs, 62 (28%) could have been prevented. The main outcome of this trial was the change in the proportion of ADEs in elderly patients in the intervention-units, compared to the control group. The main errors were: to high a dose (26%), double therapy (21%), under dose (13%), inappropriate drug (13%), drug-drug interaction (6%), previous same adverse drug reaction (3%) and miscellaneous (11.18%). After a specific educational intervention program, there were fewer ADEs in the intervention group (n = 38, 22%) than in the control group (n = 63, 36%; p = 0.004). CONCLUSION: Educational programs could help reduce the prevalence of ADEs by 14% and encourage physicians to change outdated prescription habits.

Distribution of preproenkephalin, preprotachykinin A, and preprodynorphin mRNAs in the rat nucleus accumbens: effect of repeated administration of nicotine.

The effects of a repeated treatment with nicotine on the expression of mRNAs encoding preproenkephalin (PPE), preprotachykinin-A (PPT-A), and preprodynorphin (PPDYN) were examined by in situ hybridization histochemistry in various subregions of the nucleus accumbens (Acb). In saline-treated rats, optical density measurements on autoradiographic films showed marked anteroposterior decreasing gradients for PPE and PPT-A mRNAs in the rostral pole and the core, in the cone, and in the ventral shell of the Acb, whereas a lower anteroposterior gradient was observed for PPDYN mRNA signals. The intensity of the three mRNA signals also varied according to Acb subregion. However, analysis of percentages of prepropeptide mRNA-containing neurons as compared to total neurons showed, in the rostral pole, the core, and the cone, a similar percentage of PPE mRNA (around 45%)- and PPT-A mRNA (around 40%)-expressing neurons. The ventral shell can be distinguished from the other subregions by a lower percentage of PPE mRNA (35.8%)- and PPT-A mRNA (30.6%)-expressing neurons. The percentage of PPDYN mRNA-containing neurons, by contrast, was similar (around 37%) in the core, the cone, and the ventral shell. Repeated nicotine administration increases the PPE mRNA level in the rostral pole and the anterior third of the core without any change in PPT-A and PPDYN mRNA levels in the various Acb subregions examined. The PPE mRNA increase does not support an effect mediated through an interaction of nicotine with DA neurons. The effect could be linked to a nicotine activation of other afferents to the anterior Acb and/or to a direct nicotine stimulation of PPE mRNA neurons.

Polyclonal antibodies against the rat NK1 receptor: characterization and localization in the spinal cord.

We have developed antibodies against the NK1 receptor and have investigated its cellular distribution. Rabbit polyclonal antibodies were generated against peptide (19-32) of the rat brain NK1 receptor. They were very specific to the NK1 site as shown by ELISA against various epitopes of NK1, NK2 and NK3 receptors and by immunoblotting of proteins from bacteria transfected with rat brain NK1 receptor cDNA and from rat cortex. Determining how immunostained NK1 receptors are distributed in the rat spinal cord made it possible to identify the cellular structures on which NK1 receptors are located and where they form synapses with SP terminals. In the superficial layers of the dorsal horn, the NK1 receptors appeared mainly of dendritic nature and were, like SP, abundant. In the deep layers of the dorsal horn and in the ventral horn, they were associated mostly with cell bodies.

Enterotoxin production in different Staphylococcus aureus biotypes isolated from food and meat plants.

Strains of Staphylococcus aureus isolated in Belgium and Zaïre from food and from various sources in the meat industry were biotyped, phage typed and tested for staphylococcal enterotoxin (SE) production. Thirty of the 185 strains examined produced one or more SE, and 23 of these belonged to the human biotype. Most SE-positive strains belonged to phage groups III and Mixed, or were not typable. None of the poultry-like biotype strains, which were frequent in nasal carriers among workers in meat plants as well as in minced meat, produced enterotoxins. Avian biotype strains similarly were negative.

Characterization of Staphylococcus aureus and Salmonella spp. strains isolated from bovine meat in Zaïre.

A large majority (87.4%) of 190 Staphylococcus aureus isolates from fresh beef in Lubumbashi (Zaïre) belonged to the human St. aureus ecovar; 81.2% of the phage-typed human strains were partially or solely lysed by phages of group III. Thirteen of the 52 tested strains (25.0%) were enterotoxin producers; nine of these (69.2%) were positive for staphylococcal enterotoxin A. Sixteen serotypes were identified among the 122 Salmonella isolates and nearly all these strains were susceptible to the 8 different antibiotics tested.

[Antidiuretic hormone, the renin-angiotensin system and anesthesia]. / Hormone antidiurétique, système rénine angiotensine et anesthésie.

The authors, on the basis of the literature and their own studies, envisage the behaviour of the renin-angiotensin system and of ADH during anesthesia. With regard to renin-angiotensin, it would seem that the changes reported in the past are due to the surgical procedure itself or result form haemodynamic changes but that no anesthetic has a direct effect upon the secretion of renin. For ADH, three concepts must be borne in mind: not only is secretion not influenced by anesthetics, but on the contrary anaesthesia decreases the "vasopressin" response to surgical stress. By contrast, the surgical procedure may induce the secretion of ADH responsible for coronary vasoconstriction. Finally, at high doses, ADH would appear to have an inverse antinatriuretic effect resulting in a sodium diuresis.

[Radioautographic identification of central monoaminergic neurons by local micro-instillation of tritiated serotonin or noradrenaline in cats]. / Identification radioautographique de neurones monoaminergiques centraux par micro-instillation locale de sérotonine ou de noradrénaline tritiée chez le Chat.

Monoaminergic neurons in nuclei raphe dorsalis and locus coeruleus of the Cat may be visualized by radioautography after local micro-instillation of tritiated serotonin and noradrenaline. The concomitant administration of the appropriate tracer with the other biogenic amine in non radioactive form permits a specific identification of serotoninergic and catecholaminergic nerve cell bodies. A small contingent of presumptive serotoninergic neurons is thus demonstrated in the region of the locus coeruleus.