Effect of a pharmacist-led educational intervention on clinical outcomes: a randomised controlled study in patients with hypertension, type 2 diabetes and hypercholesterolaemia.

OBJECTIVES: In recent years, hospital pharmacists have gained more importance in the clinical support of patients. However, most of the studies evaluating the impact of clinical pharmacy have only studied patients' adherence or satisfaction. The aim of this study was to evaluate the direct clinical outcomes of a pharmacist-led educational intervention in patients with chronic disease. METHODS: We conducted a randomised, controlled, parallel, physician-blinded study in a day hospital and a consultation unit of a French teaching hospital over a 1-year period. Patients with hypertension, type 2 diabetes or hypercholesterolaemia who did not reach their therapeutic goals despite drug therapy were eligible. Patients in the intervention group received an intervention from a hospital pharmacist who provided patient education on pathology and drug management. The primary outcome was the proportion of patients reaching their therapeutic goals for blood pressure, glycated haemoglobin level or low-density lipoprotein cholesterol level at the 3-month follow-up consultation. RESULTS: From January to December 2015, 89 patients were included and 73 completed the study. In the intervention group, 61.7% (21/34) of the patients reached their therapeutic goals compared with 33.3% (13/39) in the control group (p=0.015). The intervention was significantly more effective in polypharmacy patients (60.0% (12/20) vs 16.7% (4/24); p=0.005), in those aged >60 years (57.9% (11/19) vs 26.1% (6/23); p=0.037) and in patients with a high education level (68.8% (11/16) vs 29.4% (5/17); p=0.024). CONCLUSION: A single pharmacist-led educational intervention has a clinical impact, doubling the proportion of patients reaching their therapeutic goals at 3 months, especially in polypharmacy patients and those aged >60 years. This study confirms the value of clinical involvement of hospital pharmacists in patient care in a consultation unit and day hospital.

Academic pediatric clinical research: factors associated with study implementation duration.

BACKGROUND: The ethical, methodological, and technical aspects of pediatric research, often results in complications and delays in implementation. Our objective was to identify factors associated with the implementation duration of hospital-based pediatric studies. METHODS: All hospital-based pediatric studies sponsored by AP-HP between 2002 and 2008 were retrospectively identified. Association of the funding mechanism and methodological factors with the implementation duration was assessed using a multivariable mixed linear model. Pharmaceutical factors were explored as part of a subgroup analysis restricted to the studies involving drug therapy. Given that we took an exploratory approach, factors associated with implementation duration with p < 0.10 were kept in the final models. RESULTS: A total of 139 studies were evaluated. The median implementation duration was 17.1 months (range: 0.9-55.3 months), and tended to increase over time (from 14.9 [25(th) percentile-75(th) percentile: 11.5-19.9] months in 2002 to 23.7 [15.2-31.0] months in 2008, p = 0.01). External (coefficient [95 % confidence interval]: -7.7 [-11.9;-3.5] months, p < 0.001) and internal funding (-5.3 95 % CI [-9.8;-0.8], p = 0.02) compared to governmental funding and number of centers (-0.1 95 % CI[-0.2;0.02] months for 1 center increase, p = 0.07) were associated with reduced duration, whereas interventional study (either involving drug therapy (6.0 95 % CI[0.7;11.3] months, p = 0.03 or not (3.5 95 % CI[-0.3;7.3] months, p = 0.06) was associated with increased duration compared to observational study. Regarding the 35 studies involving drug therapy, external funding decreased duration (-6.7 95 % CI[-13.2;-0.2] months, p = 0.05), whereas studies involving solely a pediatric population (7.8 95 % CI[1.1;14.5] months, p = 0.01) (compared to mixed adult-pediatric population), a placebo-controlled design (6.6 95 % CI[0.9;12.3] months, p = 0.01), and inappropriate drug formulation for at least one drug used in the study (6.9 95 % CI[-0.2;14.0] months, p = 0.06) were associated with increased duration. CONCLUSION: Implementation of hospital-based pediatric studies primarily faced delays when they were interventional and, in particular, when they involved drug therapy. Regarding the latter, difficulties that resulted in delayed studies arose with respect to the supply of drugs and placebo in age-appropriate dosages and route of administration. Therefore, difficulties related to the use of pharmaceuticals need to be anticipated earlier in order to avoid implementation delays.

Off-label and unlicensed utilisation of medicines in a French paediatric hospital.

BACKGROUND: Off-label or unlicensed medicine use is very common in paediatric practice, ranging from 11 to 80 %, and is one of the predisposing factors for adverse events (23-60 %). Medicine indications are the third leading reason for doctors to perform off-label prescriptions. OBJECTIVE: The aim of our study was to determine the prevalence and nature of off-label and unlicensed medicine prescriptions in children and propose methods for risk reduction and management. SETTING: 475 bed maternity-paediatric university hospital. METHOD: Retrospective cross-sectional study lasting 1 day on new prescriptions issued over the previous 24 h by departments using electronic prescribing. Age and indication were compared to those in the French independent formulary Thériaque(®) database. MAIN OUTCOME MEASURE: Number of off-label/unlicensed prescriptions, number of patients, proportion of off-label/unlicensed prescriptions by age group, treatment class and International Non proprietary Name (INN), using the established classification. RESULTS: A total of 315 prescription medicines were analysed for 120 patients, of average age 5.1 years old. For the classification of medicine utilisation, the majority of the medicines were prescribed as licensed (190/60.3 %), followed by off-label (115/36.5 %) and unlicensed (10/3.2 %) medicines. Alimentary tract, metabolic and nervous system medicines constituted the most widely prescribed ATC classes. At least 54 % of patients received an off-label/unlicensed medicine. The indications for these were mainly for off-label prescriptions (80/25.4 %) followed by medicines not evaluated for safety and regarding safety and efficacy in children (14/4.5 %). Pantoprazole was the most widely prescribed off-label INN for stress ulcer prevention (62 %). For risk reduction, we found esomeprazole being prescribed instead of pantoprazole; esomeprazole is indicated for children under a year old. CONCLUSION: This study reflects one given day: 36.5 % of off-label prescriptions and 3.2 % of unlicensed prescriptions in a paediatric setting. Few risk reductions for off-label number prescriptions have been found. This work confirmed the necessity of carrying out further studies in children.

High-alert medications in a French paediatric university hospital.

RATIONALE, AIMS AND OBJECTIVES: High-alert medications (HAMs) are medications that are associated with a high risk of serious harm if used improperly. The objective of this study was to identify paediatric HAM used in our institution and to identify safety measures for their use. METHODS: The list of HAM and the list of safety measures that were introduced in our department were based on (1) a literature search; (2) a survey of health care professionals in our department including doctors, head nurses, nurses and pharmacists; and (3) the drug steering committee. RESULTS: We found four lists of HAM based on a literature search, including 27 classes of pharmaceutical agents, and 63 common drug names. The response rate of the survey was 20.7% (230 of 1113). Some of the HAMs included in our list were not identified by the literature search. These included neuroleptic drugs, anti-malarial agents, antiviral agents, anti-retroviral agents and intravenous acetaminophen. The drug steering committee selected 17 HAM and highlighted 53 safety measures involving seven broad aspects of pharmacological management. CONCLUSIONS: This project was part of the new safety strategies developed in a paediatric hospital. We set out to make a list of HAM relevant to paediatrics with additional safety measures to prevent medication errors associated and a 'joker' system. The various safety measures, such as double-checking of HAM prescriptions, should be reviewed during the year following their implementation. This list, which was developed in our hospital specifically for use in paediatrics, can be adapted for use in other paediatric departments.

How to improve the implementation of academic clinical pediatric trials involving drug therapy? A qualitative study of multiple stakeholders.

OBJECTIVE: The need for encouraging pediatric drug research is widely recognized. However, hospital-based clinical trials of drug treatments are extremely time-consuming, and delays in trial implementation are common. The objective of this qualitative study was to collect information on the perceptions and experience of health professionals involved in hospital-based pediatric drug trials. METHODS: Two independent researchers conducted in-depth semi-structured interviews with principal investigators (n = 17), pharmacists (n = 7), sponsor representatives (n = 4), and drug regulatory agency representatives (n = 3) who participated in institutionally sponsored clinical trials of experimental drugs in pediatric patients between 2002 and 2008. RESULTS: Dissatisfaction was reported by 67% (16/24) of principal investigators and pharmacists: all 7 pharmacists felt they were involved too late in the trial implementation process, whereas 11 (65%) principal investigators complained of an excessive regulatory burden and felt they were insufficiently involved in the basic research questions. Both groups perceived clinical trial implementation as burdensome and time-consuming. The sponsor and regulatory agency representatives reported a number of difficulties but were not dissatisfied. CONCLUSIONS: The heavy burden related to regulatory requirements, and suboptimal communication across disciplines involved, seem to be the main reasons for the major delays in pediatric drug trial implementation. The pharmaceutical aspects are intrinsically tied to trial methodology and implementation and must therefore be examined, in particular by involving Clinical Research Pharmacists at early stages of study conception.

Pediatric drug-related problems: a multicenter study in four French-speaking countries.

BACKGROUND: Pediatric intensive care patients represent a population at high risk for drug-related problems. There are few studies that compare the activity of clinical pharmacists between countries. OBJECTIVE: To describe the drug-related problems identified and interventions by four pharmacists in a pediatric cardiac and intensive care unit. SETTING: Four pediatric centers in France, Quebec, Switzerland and Belgium. METHOD: This was a six-month multicenter, descriptive and prospective study conducted from August 1, 2009 to January 31, 2010. Drug-related problems and clinical interventions were compiled from four pediatric centers in France, Quebec, Switzerland and Belgium. Data on patients, drugs, intervention, documentation, approval and estimated impact were compiled. MAIN OUTCOME MEASURE: Number and type of drug-related problems encountered in a large pediatric inpatient population. RESULTS: A total of 996 interventions were recorded: 238 (24 %) in France, 278 (28 %) in Quebec, 351 (35 %) in Switzerland and 129 (13 %) in Belgium. These interventions targeted 270 patients (median 21 months old, 53 % male): 88 (33 %) in France, 56 (21 %) in Quebec, 57 (21 %) in Switzerland and 69 (26 %) in Belgium. The main drug-related problems were inappropriate administration technique (29 %), untreated indication (25 %) and supra-therapeutic dose (11 %). The pharmacists' interventions were mostly optimizing the mode of administration (22 %), dose adjustment (20 %) and therapeutic monitoring (16 %). The two major drug classes that led to interventions were anti-infectives for systemic use (23 %) and digestive system and metabolism drugs (22 %). Interventions mainly involved residents and all clinical staff (21 %). Among the 878 (88 %) proposed interventions requiring physician approval, 860 (98 %) were accepted. CONCLUSION: This descriptive study illustrates drug-related problems and the ability of clinical pharmacists to identify and resolve them in pediatric intensive care units in four French-speaking countries.

The role of community pharmacists in the management of hematopoietic stem cell transplant recipients: knowledge and training.

INTRODUCTION: The patients receiving hematopoietic stem cell transplantation (HSCT) require routine management: the role of the pharmacist has not been extensively considered. This study had 2 aims: to explore the knowledge of community pharmacists relating to pediatric HSCT and to evaluate their expectations in terms of training needs. MATERIALS AND METHODS: We interviewed 40 community pharmacists in May and June 2010 in Paris (France) with a 3 parts questionnaire: information concerning the community pharmacy, analysis of 2 pediatric prescriptions and knowledge about HSCT and professional training. RESULTS: Twenty-nine (72.5%) of the 40 community pharmacies agreed to participate in the study. When asked what pharmacological advice they would give for an episode of fever, 13% of the pharmacists asked said that they would deliver acetaminophen without asking any further questions. Concerning hypertrichosis in patients treated with corticosteroids and ciclosporin, none mentioned the role of ciclosporin. The erroneous indications for HSCT given included road accidents (1 pharmacist; 3.4%) and hemophilia (3 pharmacists; 10.3%). Almost 80% of the pharmacists questioned considered their HSCT knowledge insufficient for their professional practice. An E-learning session adapted to their needs was of interest to almost three quarters of the pharmacists questioned.

The future of pharmaceutical care in France: a survey of final-year pharmacy students' opinions.

BACKGROUND: In the last decades, the provision of pharmaceutical care by community pharmacists has developed in OECD countries. These developments involved significant changes in professional practices and organization of primary care. In France, they have recently been encouraged by a new legal framework and favored by an increasing demand for health care (increase in the number of patients with chronic diseases) and reductions in services being offered (reduction in the number of general practitioners and huge regional disparities). OBJECTIVES: This study aimed to investigate final-year pharmacy students' opinions on 1/expanding the scope of pharmacists' practices and 2/the potential barriers for the implementation of pharmaceutical care. We discussed these in the light of the experiences of pharmacists in Quebec, and other countries in Europe (United Kingdom and the Netherlands). METHODS: All final-year students in pharmaceutical studies, preparing to become community pharmacists, at the University Paris-Descartes in Paris during 2010 (n = 146) were recruited. All of them were interviewed by means of a questionnaire describing nine "professional" practices by pharmacists, arranged in four dimensions: (1) screening and chronic disease management, (2) medication surveillance, (3) pharmacy-prescribed medication and (4) participation in health care networks. Respondents were asked (1) how positively they view the extension of their current practices, using a 5 point Likert scale and (2) their perception of potential professional, technical, organizational and/or financial obstacles to developing these practices. RESULTS: 143 (97.9%) students completed the questionnaire. Most of practices studied received a greater than 80% approval rating, although only a third of respondents were in favor of the sales of over-the-counter (OTC) drugs. The most significant perceived barriers were working time, remuneration and organizational problems, specifically the need to create a physical location for consultations to respect patients' privacy within a pharmacy. CONCLUSIONS: Despite remaining barriers to cross, this study showed that future French pharmacists were keen to develop their role in patient care, beyond the traditional role of dispensing. However, the willingness of doctors and patients to consent should be investigated and also rigorous studies to support or refute the positive impact of pharmaceutical care on the quality of care should be carried out.

Molecular dynamics study of a phospholipid monolayer at a water/triglyceride interface: towards lipid emulsion modelling.

In order to mimic the surface of parenteral nutrition emulsion droplets, the first molecular dynamics simulation of a palmitoyloleoylphosphatidylcholine (POPC) monolayer at a water/triglyceride (trilinoleoylglycerol, LLL) interface was performed. Triglyceride influence was evaluated by comparing computed phospholipid properties to the ones in a similarly modelled hydrated POPC bilayer. As expected, polar head properties (molecular area, lipid hydration, headgroup orientation) were not affected by triglycerides. In contrast, slight differences were observed on phospholipid alkyl tail region (order parameter, diffusion, Van der Waals interactions). This first approach can reasonably be extended to a further more realistic multicomponent model of clinical nutrition emulsions.

The value of near infrared spectroscopy in a small hospital compounding unit to control the risks associated with raw materials.

Pharmaceutical products, including capsules, oral suspensions, and solutions, are prepared by hospital pharmacists if no commercial product is available. Identification of the raw materials is a regulatory requirement before manufacturing (compounding). Because of the standard methods used, however, this is often time-consuming and laborious in a hospital setting. This article describes the use of near infrared spectroscopy in combination with chemometric methods for discrimination of raw materials. Sixty-three pulverized powder samples were discriminated by using reference samples (identity guaranteed by supplier and confirmed by mid infrared analyses) and NIRCal cluster analyses. A routine expert application involving optimized calibrations (n=6) was developed, which allowed a rapid and nondestructive release procedure for every powder-based raw material received. This technique is superior to established identification analyses because of reduced quarantine times and cost savings.

The use of prn medication in a child and adolescent mental health inpatient service in France.

Objective. The aim of this study was to investigate the use of "as needed" (pro re nata or prn) psychotropic medication in a child and adolescent psychiatric inpatient population. The study was carried out on the psychiatry ward of a paediatric teaching hospital in Paris, France. Methods. A prospective analysis of prn psychotropic drug prescriptions and administrations was conducted for all patients hospitalised over a period of 4 months. The study group consisted of 187 patients. Results. In total, 93 prn prescriptions were written, for 27% of the patients (51) but only 14% (26) received a total of 76 administrations. Antipsychotic drugs accounted for 54% of the prescriptions, anxiolytics for 33%, antiepileptic drugs for 8%, antiparkinsonian drugs for 4% and hypnotic drugs for 1%. Anxiety was the reason given for 67% of the prn administrations, with hydroxyzine used in 69% of these cases. Disruptive behaviour accounted for 22% of prn administrations, with antipsychotic drugs accounting for 88% of these administrations. Insomnia accounted for 8% of prn administrations, and antipsychotic drug-induced dystonia accounted for 3% of such administrations. Conclusion. Controlled studies are required to assess the efficacy and safety of prn medication and the conditions in which its use is indicated.

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.

Psychotropic medication use in the child and adolescent psychiatry wards of a French hospital.

OBJECTIVE: The aim of this study was to investigate the use of psychotropic medication in children and adolescents hospitalised in a psychiatric ward. METHODS: A prospective analysis of psychotropic drug prescriptions was conducted for all patients hospitalised in two acute psychiatric hospitalisation units of a paediatric teaching hospital in Paris, France. The study group consisted of 187 patients and was characterised in terms of age, sex, prior psychiatric hospitalisation and DSM-IV-Tr diagnosis. All prescriptions were assessed for off-label use. RESULTS: Overall, 46% of patients received at least one dose of psychotropic medication. Antipsychotic drugs were the most frequently prescribed drugs (44%), regardless of diagnosis. Ninety percent of patients who received antipsychotic drugs did not have psychosis. We found that 69% of the 421 prescriptions written were for off-label uses. The percentage distribution of off-label prescriptions by medication class was as follows: antipsychotic drugs, 90%; anxiolytics, 28%; stimulants, 26%; antidepressants, 89%; antiepileptic drugs, 89% and antiparkinsonian drugs, 91%. CONCLUSION: The extensive use of drugs for off-label indications in children and adolescents suggests that prospective post-marketing studies should be carried out to evaluate efficacy and safety.

Pharmacy education in France.

In France, to practice as a pharmacist, one needs a "diplome d'état de Docteur en Pharmacie" This degree is awarded after 6 or 9 years of pharmacy studies, depending on the option chosen by the student. The degree is offered only at universities and is recognized in France as well as throughout the European Union. Each university in France is divided into faculties called Unité de Formation et de Recherche (UFR). There are 24 faculties of pharmacy or UFRs de pharmacie. A national committee develops a pharmacy education program at the national level and each faculty adapts this program according to its specific features and means (eg, faculty, buildings). The number of students accepted in the second year is determined each year by a Government decree (numerus clausus). Successive placements, totalling 62 weeks, progressively familiarize the student with professional practice, and enable him/her to acquire the required competencies, such as drug monitoring and educating and counselling patients. Challenges facing community pharmacies in the next 10 years are patient education, home health care, and orthopaedics; in hospital pharmacies, empowering pharmacists to supervise and validate all prescriptions; and finally, research in pharmacy practice.

Lack of commercial oral drug formulations for children in two hospital group purchasing agreements in france and Canada.

There are a limited number of commercial oral pediatric drug formulations on the market. The incidence of available commercial oral formulations for children has not been studied to date. This study compared the number and the characteristics of oral pediatric drug formulations listed on two hospital group purchasing agreements for the two large urban areas (e.g., Paris and Montreal), valid on April 1, 2006. Variables collected were the brand and the generic name product, the anatomical therapeutic chemical classification, the drug formulation, and the dispensing tool. Throughout this study, we identified that there was a total of 191 and 151 commercial oral pediatric drug formulations corresponding to 127 and 94 generic name products, respectively in Paris and Montreal. The three main anatomical therapeutic chemical classification classes are alimentary tract and metabolism drugs, systemic anti-infectives, and drugs acting on nervous system. There are only 47 generic names common to both group purchasing agreements. Also, our study provides examples of discrepancies between countries in terms of availability of commercial oral drug formulation for children. Market globalization should contribute to reduce these differences in the limited number of commercial oral pediatric drug formulations.

Comparison of pain management in paediatric surgical patients in two hospitals in France and Canada.

OBJECTIVE: Pain management in children has improved substantially over the last few years but continues to vary widely across institutions. Our objective was to describe the evaluation and treatment of pain in paediatric patients in two hospitals (Robert Debré in Paris, France, and Sainte-Justine, Montréal, Canada) and to compare conformity with quality criteria. METHOD: Retrospective medical chart of a total of 200 patients with uncomplicated appendectomy, spinal fusion, ureteroneocystostomy, or laparoscopic cholecystectomy were analysed, with special attention to nurses' entries, prescriptions, and medication administration sheets. MAIN OUTCOME MEASURE: Patient characteristics and variables pertaining to pain evaluation (tool and result) and treatment (date, prescription and administration details) were collected. Quality criteria for evaluating conformity with guidelines were taken from the literature. Any change in medication, dosage, or dosing interval was taken as a new prescription. RESULTS: About 929 prescriptions and 2,388 numerical pain scores were recorded for 200 patients. Pain was recorded at 70.8% of vital-sign evaluations at the Robert-Debré Hospital compared to 30.9% at the Sainte-Justine hospital (P < 0.0001). A validated age-appropriate pain evaluation tool was used in 97.4 and 94.1% of evaluations in these two hospitals, respectively (P < 0.0001). Analgesic dosage was appropriate in 92.5% of prescriptions at Robert-Debré and 86.0% of those at Sainte-Justine (P = 0.002). CONCLUSION: This study documents differences in post-operative pain management between two paediatric hospitals. We found differences between the two hospitals regarding the frequency of pain evaluation, the use of validated tools for evaluating pain, and analgesic dosages. Continued efforts to educate prescribing physicians and other healthcare providers are needed to improve pain management in children.

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

OBJECTIVE: To 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. SETTING: Centre 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. METHOD: The data were gathered from annual reports, department strategic plans and by direct observation. MAIN OUTCOME MEASURE: The description and comparison of the legal environment, hospital demographics, pharmacy department data, drug dispensing processes and pharmacist activities in the two institutions. RESULTS: The 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. CONCLUSION: There 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.

[Non-guideline use of innovative and expensive drugs in pediatrics: assessing clinical practice]. / Utilisation hors recommandations des médicaments innovants et coûteux en pédiatrie.

OBJECTIVE: The objective of this study was to analyze in a pediatric hospital the use of expensive drugs as part of the new activity-based system (T2A) of funding for French public hospitals. We identified and analyzed the therapeutic use of these drugs in indications not included in the expert recommendations issued to accompany this change, with the goal of proposing specific pediatric recommendations. METHOD: Analysis of prescriptions from May through September 2005 showed that 259 patients received expensive drugs subject to special reimbursement. The computerized prescription system enabled us to monitor and validate prescriptions daily. Indications for these expensive drugs were ranked by relevance. RESULTS: The prescriptions analyzed covered 26 expensive drugs. Among the 344 "patient-drugs", 80% were expensive drugs for an accepted therapeutic use, 5% for a pertinent therapeutic use (under evaluation), and 15% for "off-label" uses (2% "not approved" and 13% for indications not considered by the recommendations). CONCLUSION: This study showed that some therapeutic uses not approved by the official recommendations are nevertheless justified. Gathering data from other pediatric hospitals is essential to determine the need for pediatric clinical trials.

Atmospheric pressure photoionization coupled to porous graphitic carbon liquid chromatography for the analysis of globotriaosylceramides. Application to Fabry disease.

Globotriaosylceramides (Gb(3)) are biological compounds implicated in Fabry disease, a lysosomal storage disease due to the deficient activity of alpha-D-galactosidase A, which results in an accumulation of Gb(3) in many organs. The naturally occurring samples are composed of mixtures of several molecular species differing by the structure of the alkyl chains and the nature of the sphingoid base. Atmospheric pressure photoionization mass spectrometry (APPI-MS) proved to be an efficient method for the analysis of globotriaosylceramide molecular species, both in direct injection and by coupling with liquid chromatography (LC). In the positive ion mode, in-source fragmentations yield very precious information that can be used to determine the structure of the alkyl chains. In the negative ion mode, the chloroform solvent participates to the analyte ionization by forming an adduct with chloride ions generated in situ. Combination of LC on a Porous Graphitic Carbon stationary phase and APPI-MS allowed the detection of a great number of species from biological samples isolated from Fabry patients. This method could be an interesting analytical tool for the biochemical investigation of (sphingo) lipid metabolism.

Drug administration errors and their determinants in pediatric in-patients.

OBJECTIVE: . To quantify the type and frequency of drug administration errors to pediatric in-patients and to identify associated factors. DESIGN: Prospective direct-observation study of drug administration errors from April 2002 to March 2003. SETTING: Four clinical units in a pediatric teaching hospital. STUDY PARTICIPANTS: Twelve observers accompanied nurses giving medications and witnessed the preparation and administration of all drugs to all patients on all weekday mornings. INTERVENTION: None. MAIN OUTCOME MEASURE: Discrepancies between physicians' orders and actual drug administration. RESULTS: During the 1719 observed administrations to 336 patients by 485 nurses, 538 administration errors were detected, involving timing (36%), route (19%), dosage (15%), unordered drug (10%), or form (8% form). These errors occurred for 467 (27%) of the 1719 administrations. Intravenous drugs (OR = 0.28; CI = 0.16-0.49; versus miscellaneous) were associated with fewer errors. Error rates were higher for cardiovascular (OR = 3.38; CI = 1.24-9.27; versus miscellaneous) and central nervous system drugs (OR = 2.65; CI = 1.06-6.59; versus miscellaneous); unspecified dispensing system (OR = 2.06; CI = 1.29-3.29; versus store in the unit); non-intravenous non-oral administration (OR = 4.44; CI = 1.81-10.88; versus oral administration); preparation by the pharmacy (OR = 1.66; CI = 1.10-2.51); and administration by a hospital pool nurse, temporary staffing agency nurse, or nurse intern (OR = 1.67; CI = 1.04-2.68; versus registered full-time nurse). Each additional management procedure in the patient increased the risk of error (OR = 1.22; CI = 1.01-1.48). CONCLUSIONS: The risk factors identified in our study should prove useful for designing preventive strategies, thereby improving the quality of care.