The clinical impact of medication reconciliation on admission to a French hospital: a prospective observational study.

OBJECTIVE: This study was designed to assess the clinical impact of medication reconciliation using two criteria: the number of inpatients who had experienced at least one medication error; the severity of the potential harm associated with these detected errors. METHOD: The study was a prospective observational one. The eligible population included patients aged 65 and over subjected to medication reconciliation at admission. The potential severity of medication errors was evaluated independently by the physician in charge of the patient and by the pharmacist involved in the medication reconciliation process. Severity assessment took account of the drug(s) involved in the error, the type of medication error, and the patient's clinical and biological data. RESULTS: From January 2011 to September 2012, 1799 medication errors were recorded among the 1670 patients subjected to medication reconciliation who were hospitalised from the emergency department. At least one medication error occurred for 744 (44.6%) of these patients. There were 87 medication errors associated with potentially major severity (5.6%). These concerned 67 patients (4.2%). The most prevalent error was omission. Cardiovascular and anticoagulant drugs were the drugs most frequently involved in these serious medication errors. Arrhythmia, haemorrhage, thrombosis, hyperglycaemia and hypoglycaemia were identified as the most likely harms that could have occurred. CONCLUSIONS: The detection of cases of serious potential harm shows the clinical impact of medication reconciliation. It would be interesting to perform a multicentred assessment using indicators such as the number of inpatients experiencing at least one serious medication error. This could help to promote medication reconciliation as essential for patient safety.

Development and multi-centre evaluation of a method for assessing the severity of potential harm of medication reconciliation errors at hospital admission in elderly.

BACKGROUND: Medication reconciliation is a powerful process to correct medication errors (ME) resulting from miscommunicated information at transitions of care. This study aims to develop and evaluate a scoring method for assessing the severity of potential harm of ME intercepted by medication reconciliation at hospital admission in elderly. METHODS: The development of the scoring method was based on a literature search and the creation of a list of high-risk drugs used in outpatient care. The evaluation of the method was carried out in 7 French hospitals and was based on two criteria: the inter-rater reliability and acceptability. The assessment of the inter-rater reliability was based on intra-class correlation coefficient (ICC) calculations. Each hospital prospectively enrolled the 10 first patients aged 65 or older presenting with at least one ME. Seven blocks of 10 patients were formed. After randomization, each block was rated by practitioners from 3 hospitals. The assessment of the acceptability was based on a satisfaction questionnaire. RESULTS: A clinical algorithm was developed. The inter-rater reliability of the method was validated by the overall agreement of the 7 hospitals ratings. The agreement was at least substantial (ICC>0.60) and in most of cases almost perfect (ICC>0.80). The acceptability of the method was judged as satisfactory. CONCLUSION: This multi-centre project has validated an instrument for assessing the severity of potential harm of ME intercepted by medication reconciliation. This will allow studies to be conducted with large cohorts of patients in order to develop epidemiological databases of ME of potential clinical significance.

CYP98A22, a phenolic ester 3'-hydroxylase specialized in the synthesis of chlorogenic acid, as a new tool for enhancing the furanocoumarin concentration in Ruta graveolens.

BACKGROUND: Furanocoumarins are molecules with proven therapeutic properties and are produced in only a small number of medicinal plant species such as Ruta graveolens. In vivo, these molecules play a protective role against phytophageous insect attack. Furanocoumarins are members of the phenylpropanoids family, and their biosynthetic pathway is initiated from p-coumaroyl coA. The enzymes belonging to the CYP98A cytochrome P450 family have been widely described as being aromatic meta-hydroxylases of various substrates, such as p-coumaroyl ester derivatives, and are involved in the synthesis of coumarins such as scopoletin. In furanocoumarin-producing plants, these enzymes catalyze the step directly downstream of the junction with the furanocoumarin biosynthetic pathway and might indirectly impact their synthesis. RESULTS: In this work, we describe the cloning and functional characterization of the first CYP98A encoding gene isolated from R. graveolens. Using Nicotiana benthamiana as a heterologous expression system, we have demonstrated that this enzyme adds a 3-OH to p-coumaroyl ester derivatives but is more efficient to convert p-coumaroyl quinate into chlorogenic acid than to metabolize p-coumaroyl shikimate. Plants exposed to UV-B stress showed an enhanced expression level of the corresponding gene. The R. graveolens cyp98a22 open reading frame and the orthologous Arabidopsis thaliana cyp98a3 open reading frame were overexpressed in stable transgenic Ruta plants. Both plant series were analyzed for their production of scopoletin and furanocoumarin. A detailed analysis indicates that both genes enhance the production of furanocoumarins but that CYP98A22, unlike CYP98A3, doesn't affect the synthesis of scopoletin. CONCLUSIONS: The overexpression of CYP98A22 positively impacts the concentration of furanocoumarins in R. graveolens. This gene is therefore a valuable tool to engineer plants with improved therapeutical values that might also be more resistant to phytophageous insects.

Agrobacterium-mediated transformation of Ruta graveolens L.

Agrobacterium tumefaciens is used to develop a genetic transformation method for a medicinal plant Ruta graveolens. The direct plant regeneration strategy is preferred to callus line establishment. In vitro seedlings, 2- -to 3-wk-old, are used to excise hypocotyls and co-cultivated for 3 d with A. tumefaciens strain C58C1Rif containing plasmid pTDE4 harbouring neomycin phosphotransferase (npt II, kanamycin resistance) and beta-glucuronidase encoding genes. The Southern blot analysis has shown that 78% kanamycin resistant plants contain gene encoding beta-glucuronidase. The GUS histochemical assay shows that 67% transgenic plants exhibit the corresponding enzymatic activity. Routine transformation efficiency of R. graveolens L. is 11% and could reach up to 22%. Transgenic plants are grown in the greenhouse within 4 months after the initial seedlings.