Olivier Bourdon

Fungicidal properties of meso-arylglycosylporphyrins: influence of sugar substituents on photoinduced damage in the yeast Saccharomyces cerevisiœ

A series of neutral meso-arylglycosylporphyrins has been tested in order to evaluate their potency as antifungal agents against the yeast Saccharomyces cerevisiae. Photodynamic activity of these molecules results in intracellular damage as evidenced by the loss of clonogenicity and DNA fragmentation. The ability of these photosensitizers to permeate yeast cells is determined by microspectrofluorimetry and is correlated with their antifungal potency. Amphiphilic porphyrin derivatives are shown to exhibit the more pronounced photoactivity.

Analysis of overridden alerts in a drug-drug interaction detection system

OBJECTIVE The aim of this study was to evaluate the relevance of the signals generated by a computerized drug-drug interaction detection system and to design a classification of overridden drug-drug interaction alerts. STUDY DESIGN Prospective study over two months. SETTING Five hundred and ten-bed university paediatric hospital. MAIN OUTCOME MEASURES In Robert Debré Hospital physicians generate drug orders online using a computerized physician order entry system that also detects drug-drug interactions in real time. We analysed the relevance of a sample of alerts overridden by physicians. RESULTS We analysed a sample of 613 overridden alerts. We defined three categories of overridden alerts: informational errors (35); system errors (244) and accurate alerts (334). Two reasons account for 40% of false-positive alerts: an inability of the system to recognize real conflicts between drug treatments and guidelines stating that the two drugs can be used together, because the benefit outweighs the risk of side effects due to the drug-drug interaction. CONCLUSIONS We created a classification of overridden alerts, in the context of computerized physician order entry system coupled with a drug-drug interaction detection system. There is clearly room for improvement in the development of drug-drug interaction software. This classification should make it possible to break this work down into smaller tasks, making it possible to decrease the sensitivity to background noise of drug-drug interaction detection systems.

Impact of implementing French antibiotic guidelines for acute respiratory-tract infections in a paediatric emergency department, 2005-2009.

Acute respiratory tract infections (ARTIs) are the main reason for antibiotic prescription in children. In 2005, the French Drug Agency published guidelines to minimise inappropriate use of antibiotics for ARTI. The purpose of this study was to assess the impact of implementing these guidelines in a paediatric emergency department. We retrospectively analysed data collected prospectively in a French paediatric emergency department from November 2005 (date of guideline implementation) to October 2009. For each child diagnosed with ARTI, we collected age, diagnosis, and prescribed antibiotics. We computed antibiotic prescription rates in the study population. During the study period, 53,055 children were diagnosed with ARTI and 59% of the 22,198 antibiotic prescriptions given at discharge were related to ARTI. The proportion of ARTI patients given antibiotic prescriptions fell from 32.1% during the first year to 21% in year 4 (p < 10−4, Cochran-Armitage test). Amoxicillin-clavulanic acid and amoxicillin accounted for 50% and 34% of antibiotic prescriptions for ARTI, respectively. French antibiotic guidelines led to significant decreases in antibiotic prescription for ARTI in our paediatric emergency department.

Enhancement of 5,10,15,20-Tetra(m-Hydroxyphenyl)chlorin Fluorescence Emission by Inclusion in Natural and Modified Cyclodextrins

Fluorescence properties of 5,10,15,20-tetra(m-hydroxyphenyl)chlorin (m-THPC), a sensitizer used in photodynamic therapy (PDT), were studied in the presence of three native cyclodextrins (CDs) -α, -β, and γ-CD—and two modified cyclodextrins—heptakis (2,6-di-O-methyl) β-CD (Me-β-CD) and heptakis (2-O-hydroxy-propyl) β-CD (HP-β-CD). The CDs studied have been shown to undergo the formation of an inclusion complex with m-THPC, leading to a large enhancement (up to 300 times) of m-THPC fluorescence intensity depending on the CD used. Stoichiometry and association constants have been determined on the basis of the variation of fluorescence intensity. A 1:2 stoichiometry has been found for m-THPC complexes with γ-CD, Me-β-CD, and HP-β-CD. Association constants as high as K = 9.5 × 108 M−2 in the case of m-THPC/2Me-β-CD and K = 2.7 × 109 M−2 in the case of m-THPC/ 2HP-β-CD complex were determined, whereas a lower value (K = 2.4 × 104 M−2) was found in the case of m-THPC/2γ-CD. Because of the highest fluorescence enhancement (a factor of about 300) observed with Me-β-CD, this compound would be the most suitable to improve the detection of m-THPC in further pharmacokinetics and biodistribution studies.

Comparison of hospital pharmacy practice in France and Canada: can different practice perspectives complement each other?

ObjectiveTo compare hospital pharmacy practice in France and Canada by identifying similarities and differences in the two institution’s pharmacy activities, resources, drug dispensing processes and responsibilities.SettingCentre hospitalier universitaire Sainte-Justine (SJ), Montréal, Québec, Canada and Hôpital Robert Debré (RD), Paris, France, are two maternal-child teaching hospitals. They share a similar mission focused on patient care, teaching and research.MethodThe data were gathered from annual reports, department strategic plans and by direct observation.Main outcome measureThe description and comparison of the legal environment, hospital demographics, pharmacy department data, drug dispensing processes and pharmacist activities in the two institutions.ResultsThe Centre hospitalier universitaire Sainte-Justine and Hôpital Robert Debré are similar with respect to their mission and general demographics; number of beds, annual hospital expenditures, number of admissions, visits and childbirths. The respective pharmacy departments differ in allocated resources. The main operational differences concern compounding, quality control programs and clinical activities. The French department also manages medical devices, medical gases, blood derivatives and the sterilisation unit. These comparisons highlight the more patient-oriented Canadian hospital pharmacy practice against the more product-oriented French hospital practice Factors contributing to these differences include academic curriculum, the attention paid to the legal environment by professional bodies, staffing patterns and culture.ConclusionThere are differences between the hospital pharmacy practice in the studied hospitals in Canada and France. Hospital pharmacy practice in France seems to be more product oriented, and the practice in Canada seems more patient oriented.

POPI (Pediatrics: Omission of Prescriptions and Inappropriate prescriptions): development of a tool to identify inappropriate prescribing.

Introduction Rational prescribing for children is an issue for all countries and has been inadequately studied. Inappropriate prescriptions, including drug omissions, are one of the main causes of medication errors in this population. Our aim is to develop a screening tool to identify omissions and inappropriate prescriptions in pediatrics based on French and international guidelines. Methods A selection of diseases was included in the tool using data from social security and hospital statistics. A literature review was done to obtain criteria which could be included in the tool called POPI. A 2-round-Delphi consensus technique was used to establish the content validity of POPI; panelists were asked to rate their level of agreement with each proposition on a 9-point Likert scale and add suggestions if necessary. Results 108 explicit criteria (80 inappropriate prescriptions and 28 omissions) were obtained and submitted to a 16-member expert panel (8 pharmacists, 8 pediatricians hospital-based −50%- or working in community −50%-). Criteria were categorized according to the main physiological systems (gastroenterology, respiratory infections, pain, neurology, dermatology and miscellaneous). Each criterion was accompanied by a concise explanation as to why the practice is potentially inappropriate in pediatrics (including references). Two round of Delphi process were completed via an online questionnaire. 104 out of the 108 criteria submitted to experts were selected after 2 Delphi rounds (79 inappropriate prescriptions and 25 omissions). Discussion Conclusion POPI is the first screening-tool develop to detect inappropriate prescriptions and omissions in pediatrics based on explicit criteria. Inter-user reliability study is necessary before using the tool, and prospective study to assess the effectiveness of POPI is also necessary.

Intravenous Immunoglobulin Therapy in Pediatric Narcolepsy: A Nonrandomized, Open-Label, Controlled, Longitudinal Observational Study

STUDY OBJECTIVES Previous case reports of intravenous immunoglobulins (IVIg) in pediatric narcolepsy have shown contradictory results. METHODS This was a nonrandomized, open-label, controlled, longitudinal observational study of IVIg use in pediatric narcolepsy with retrospective data collection from medical files obtained from a single pediatric national reference center for the treatment of narcolepsy in France. Of 56 consecutively referred patients with narcolepsy, 24 received IVIg (3 infusions administered at 1-mo intervals) in addition to standard care (psychostimulants and/or anticataplectic agents), and 32 continued on standard care alone (controls). RESULTS For two patients in each group, medical files were unavailable. Of the 22 IVIg patients, all had cerebrospinal fluid (CSF) hypocretin ≤ 110 pg/mL and were HLA-DQB1*06:02 positive. Of the 30 control patients, 29 were HLA-DQB1*06:02 positive and of those with available CSF measurements, all 12 had hypocretin ≤ 110 pg/mL. Compared with control patients, IVIg patients had shorter disease duration, shorter latency to sleep onset, and more had received H1N1 vaccination. Mean (standard deviation) follow-up length was 2.4 (1.1) y in the IVIg group and 3.9 (1.7) y in controls. In multivariate-adjusted linear mixed-effects analyses of change from baseline in Ullanlinna Narcolepsy Scale (UNS) scores, high baseline UNS, but not IVIg treatment, was associated with a reduction in narcolepsy symptoms. On time-to-event analysis, among patients with high baseline UNS scores, control patients achieved a UNS score < 14 (indicating remission) less rapidly than IVIg patients (adjusted hazard ratio 0.18; 95% confidence interval: 95% confidence interval: 0.03, 0.95; p = 0.043). Shorter or longer disease duration did not influence treatment response in any analysis. CONCLUSIONS Overall, narcolepsy symptoms were not significantly reduced by IVIg. However, in patients with high baseline symptoms, a subset of IVIg-treated patients achieved remission more rapidly than control patients. COMMENTARY A commentary on this article appears in this issue on page 363.

Evaluation of frequency of paediatric oral liquid medication dosing errors by caregivers: amoxicillin and josamycin

Objective To study reconstitution and preparation dosing errors of liquid oral medications given by caregivers to children. Methods A prospective observational study was carried out in the departments of general paediatrics and emergency paediatrics at the Robert-Debré Childrens University Hospital. An interview with caregivers involved (1) practical reconstitution and preparation of an oral liquid medication from a prescription drawn at random (amoxicillin (Clamoxyl, dosing spoon) or josamycin (Josacine, dose-weight pipette)) and (2) a questionnaire about their use. Results One hundred caregivers were included. Clamoxyl and Josacine were incorrectly reconstituted in 46% (23/50) and 56% (28/50) of cases, respectively, with a risk of underdosing of Clamoxyl (16/23) and overdosing of Josacine (23/28). Dose preparation with the dosing spoon was incorrect in 56% of cases, and in 10% of cases with the dose-weight pipette. Female sex, native French speaker, and age were significantly associated with correct reconstitution. Male sex and medication were significantly associated with correct preparation. Conclusions This study highlights the high incidence of errors made by caregivers in reconstituting and preparing doses of these liquid oral medicines, which are associated with considerable risks of over- and underdosing. Factors associated with these errors have been identified which could help health professionals to optimise their strategy for educating families about the use of liquid oral medications and the need to check that they understand these instructions.

Traitement de la gale et rupture d’Ascabiol® : quid de la population pédiatrique ? Gale chez l’enfant et rupture d’Ascabiol®

Scabies is a disease in steady increase in Île-de-France region. Standard treatment, Ascabiol(®) (benzyl benzoate/sulfiram), is back-order for several months and its return remains uncertain. Facing this drug shortage, French Drug Agency (ANSM) has imported a drug from Germany, Antiscabiosum 10 % (benzyl benzoate), to treat patients having contraindications for other scabicides available in France (ivermectin, esdepallethrine). However, infants less than 1 year (<15 kg) and asthmatics infants have no alternative treatment. A multidisciplinary workgroup explored the various existing therapeutic alternatives in France and worldwide. From ANSMs recommendations and groups experience, a decision algorithm was proposed for treating patients. However, pediatric context implied the use of off-label drugs. Proposed treatments widely known by practitioners, prescriptions-types, dose, modalities of use and dispensation, and flyers to patients were realized to optimize treatment efficacy.

Randomized Controlled Trial of Parent Therapeutic Education on Antibiotics to Improve Parent Satisfaction and Attitudes in a Pediatric Emergency Department

Objective To evaluate therapeutic education delivered in a pediatric emergency department to improve parents’ satisfaction and attitudes about judicious antibiotic use. Methods In an emergency department of a tertiary pediatric hospital, children aged 1 month to 6 years and discharged with an oral antibiotic prescription for an acute respiratory or urinary tract infection were randomized to a patient therapeutic education on antibiotic use (intervention group) or fever control (control group) delivered to the parents (in the presence of the children) by a pharmacist trained in therapeutic education. Education consisted in a 30-minute face-to-face session with four components: educational diagnosis, educational contract, education, and evaluation. The main outcome measure was parent satisfaction about information on antibiotics received at the hospital, as assessed by a telephone interview on day 14. The secondary outcome was attitudes about antibiotic use evaluated on day 14 and at month 6. Results Of the 300 randomized children, 150 per arm, 259 were evaluated on day 14. Parent satisfaction with information on antibiotics was higher in the intervention group (125/129, 96.9%, versus 108/130, 83.0%; P=0.002, exact Fisher test). Intervention Group parents had higher proportions of correct answers on day 14 to questions on attitudes about judicious antibiotic use than did control-group parents (P=0.017, Mann-Whitney U test). Conclusion Therapeutic education delivered by a clinical pharmacist in the pediatric emergency department holds promise for improving the use of antibiotics prescribed to pediatric outpatients. Trial Registration ClinicalTrials.gov NCT00948779 http://clinicaltrials.gov/show/NCT00948779