[EASYSCAN: French pilot study for securing drug administration by barcode reading]. / EASYSCAN : étude pilote française pour la sécurisation de l'administration des médicaments par lecture code-barres.

OBJECTIVES: Medication errors are common at the time of administration. To prevent them, technologies allowing consistency check by bar code technology at bedside have been developed. Our study focuses on the evaluation of a BarCode Medication Administration (BCMA) called EASYSCAN with Electronic Medication Administration Record (e-MAR) to verify both patient's identity and medication to be administrated. METHODS: A prospective observational study was conducted during seven weeks in a French medicine ward. The performance of the system was evaluated by the success rate of BCMA and by the average time for administration with and without EASYSCAN. A satisfaction questionnaire about BCMA was proposed to nurses. RESULTS: We observed 182 administrations including 87 (48%) with EASYSCAN. The verification of the patient's identity was successful in 77% of administrations and 65% of the drugs were scanned successfully. The main causes of check failures were the lack of datamatrix on the drug (81%), error messages (14%) and the lack of system functionality (5%). The average time for administration per patient was significantly increased: 4.68min/patient with versus 2.87min/patient without EASYSCAN. CONCLUSIONS: The study shows the EASYSCAN's performance in its first version. Material and software evolutions and an increase of nurses'pratices will be necessary to continue the experimentation of this system still unpublished in France.

[Factors influencing the acceptability of pediatric galenic formulations]. / Facteurs influençant l'acceptabilité des formulations galéniques en pédiatrie ­ revue de la littérature.

BACKGROUND AND GOAL OF THIS STUDY: Few available galenic formulations of drugs have pediatric doses, so that many of them are used off label in children. The influence of such pharmaceutical formulation on therapeutic adherence was evaluated in a systematic review of the literature. MATERIALS AND METHODS: This search was performed in 4 data bases: Medline, the Cochrane Library, Web of Science and Science Direct. Included articles were in French or English and focused on therapeutic adherence and route of administration. RESULTS: Overall, 51 articles were included in the study: 46 from Medline (27 selected), 1 from The Cochrane Library (1 duplicate), 61 from Web of Science (13 selected) and 23 articles from Science Direct (11 selected). The two main pharmaceutical formulations studied were liquid dosage form 51% (n=28) and solid oral form 35% (n=19). DISCUSSION: Easy use of liquid forms (n=18) (easy dose adjustment and administration) was associated with good adherence. Optimization of organoleptic properties was found to improve adherence (n=20). The main limitations to the use of solid oral formulations are the risk of choking in a child under 6 and difficulty adapting doses for pediatric use. Commercialization of minitablets should help solve these problems (n=3) and therapeutic education sessions could make it possible to prescribe selected pills to children aged 4 or older (n=2). A risk of misuse because of incorrect administration seems to be the reason that aerosols are underused. CONCLUSION: Drug formulation influences therapeutic adherence in children, which is a cornerstone for successful pharmacotherapeutic management.

[Pharmacist's interventions on outpatient prescriptions in a university hospital drugs sales service]. / Interventions des pharmaciens sur les prescriptions ambulatoires dans le cadre de l'activité de rétrocession d'un centre hospitalier universitaire.

UNLABELLED: For public health reasons, some drugs are only available in hospital drugs sales service. This activity takes place in a specific risk context of organization, patients and/or drugs. A systematic prescription analysis by pharmacist contributes to securise treatment dispensed. The aim of this paper is to present the main drugs problems in the analysis of outpatient prescriptions and pharmaceutical interventions in three units of hospital drugs sales service belong to university hospital. METHODS: Throughout the year 2013, drug problems detected were recorded prospectively and systematically. RESULTS: Of the 22,279 prescriptions analyzed, 247 pharmaceutical interventions (1.1%) were detected including 27.6% of problems concerning the dosages, 15.4% the unconformity, 6.9% contraindications. Regarding ATC drugs classes, we found 43.7% for anti-infectives and 17.4% for antineoplatics. The overall acceptance rate is 81.8%. CONCLUSION: These results show the importance of the analysis of outpatient prescriptions before dispensing and the need to have all prescriptions, clinical and biological elements and to develop interprofessionality. The implementation of a platform for dematerialized data exchanges between professionals, including data from the pharmaceutical patient record should contribute to improving drug management of the patient.

Management of glioblastoma: comparison of clinical practices and cost-effectiveness in two cohorts of patients (2008 versus 2004) diagnosed in a French university hospital.

WHAT IS KNOWN AND OBJECTIVE: Therapeutic options for the management of glioblastoma (GBM) have greatly evolved over the last decade with the emergence of new regimens combining radiotherapy plus temozolomide and the use of bevacizumab at recurrence. Our aim was to assess the clinical and economic impacts of those novel strategies in our center. METHODS: A single-center retrospective chart review was conducted on patients newly diagnosed with a GBM over two periods (year 2004, group 1 or year 2008, group 2) with limitations to those eligible to radiotherapy after initial diagnosis. The type of medical management was described and compared, as well as overall survival and total costs from diagnosis to death or the last follow-up date. Cost analysis was performed under the French Sickness Fund perspective using tariffs from 2012. RESULTS: One hundred twenty-two patients were selected (49 in group 1 and 73 in group 2) with similar baseline characteristics within the two groups. Patients from group 2 received more frequently temozolomide radiochemotherapy (71% vs. 39%, P < 0·05) as first-line treatment as well as bevacizumab regimen at recurrence (48% vs. 6%, P < 0·05); the median overall survival was increased between the two periods (respectively 17 vs. 10 months, P < 0·05). The mean total cost per patient was 54,388 € in group 1 and 71,148 € in group 2 (P < 0·05). Hospital care represented the largest expenditure (76% and 58% in groups 1 and 2 respectively) followed by chemotherapy drugs costs (11% and 30% respectively). The total cost difference between the two groups was explained by the increasing use of temozolomide and bevacizumab. The incremental cost-effectiveness ratio was estimated at 54,355 € per life-year gained. WHAT IS NEW AND CONCLUSION: As far as we know, this is the first study reporting the total cost of GBM management based on the French perspective, as well as the cost-effectiveness of clinical practices in term of cost per life-year gained. Those novel strategies have contributed to improve overall survival while inducing a substantial, but acceptable, increase of total costs.

[Study of physicochemical and bacteriological impact of a weekly assembly of automated compounding BAXA(®) Exacta-Mix 2400 on parenteral nutrition admixture manufacturing]. / Étude de l'impact physicochimique et bactériologique d'un montage hebdomadaire de l'automate BAXA(®) Exacta-Mix 2400 sur la fabrication des poches de nutrition parentérale.

INTRODUCTION: The parenteral nutrition admixtures are manufactured with an automated compounding BAXA(®) Exacta-Mix 2400. A 48-hour assembly has been validated. To optimize time and cost, a weekly assembly was tested. MATERIALS AND METHODS: Assembly was made on the first day. Ten identical parenteral nutrition admixtures (different volumes and compositions) were produced each day. A macroscopic examination was done at D0, D7 and D14. Physicochemical controls (electrolytes determinations by atomic absorption spectrophotometry, osmolalities measurements) were performed. Microbiological tests included a filtration membrane sterility test (Steritest(®)) and a plate count agar environmental monitoring. RESULTS: All mixtures were considered stable. The 12 Steritest(®) (H24, H48, D7 and D14) did not show any bacterial or fungal contamination. No microorganism has been detected on the plate count agar at D4 and D7. Concerning the physicochemical parameters of each parental nutrition admixture, no significant difference (Wilcoxon test) with the first day was found. DISCUSSION AND CONCLUSIONS: The automated filling system BAXA(®) Exacta-Mix 2400 improves the quality and safety of production. According to these results, the weekly assembly is validated and permit to save time (80hours/year) and cost (40 000 euros on consumable/year).

[Stability and sterility of parenteral nutrition admixture for patients home care manufactured by the automated compounding BAXA® EM 2400]. / Étude de stabilité et de stérilité des poches de nutrition parentérale pour patients à domicile fabriquées à l'aide de l'automate BAXA® EM 2400.

INTRODUCTION: Initially, parenteral nutrition admixtures are produced by sterile filtration with a stability of 14 days This study was conducted to check the stability (physicochemical and microbiological) when automated compounding BAXA(®) EM 2400 is used. MATERIALS AND METHODS: Forty pockets corresponding to 10 patients have been manufactured in according to Good Manufacturing Practice. Macroscopic and physicochemical tests (determination of electrolytes by atomic absorption spectroscopy, osmolality and pH measurements) were performed at different times (D0, D7, D14). To complete these checks, the emulsions were analyzed (size, stability, optical microscopy) at D0 and D14. Finally, microbiological research (Bact-Alert(®), filtration membrane sterility tests Steritest(®) and plate count agar) was performed. RESULTS: No lipid cluster was observed with an optical microscope. Comparison of data observed for all controls showed no significant difference in the production of D0 by the Wilcoxon test. Microbiology (Bact-Alert filtration membrane sterility tests Steritest(®) and plate count agar) was negative for all samples. Consequently, all mixtures were considered stable. DISCUSSION AND CONCLUSIONS: The automated compounding BAXA(®) EM 2400 ensures quality and safety of production. The results of this study have shown stability and sterility of parenteral nutrition admixtures for 14 days.

[Depyrogenation test regarding inox and glass containers in the preparation of parenteral nutrition mixtures]. / Test de dépyrogénation des conteneurs en inox et en verre pour la préparation des mélanges pour nutrition parentérale.

INTRODUCTION: The preparation of parenteral nutrition mixture (PNM) in an open chamber requires the use of intermediate containers sterile and non-pyrogenic. A sterilization of containers by moist heat in large autoclaves is the suitable method. However, sterilization by moist heat is not a depyrogenation method. In our study, we report the validation of a sterilization and depyrogenation method for containers by dry heat using a convection oven. MATERIALS AND METHODS: Sterilization and depyrogenation of material by dry heat have been audited by the reduction of at least three logarithms of original endotoxin rate. The containers were initially artificially contaminated with a suspension of endotoxin for 16 hours. Contaminated containers were placed in an oven with revolving heat at 250 °C for 1 hour. After treatment with dry heat, the residual endotoxin levels in the containers were determined by a kinetic chromogenic method. RESULTS: After treatment with dry heat, the average log reductions of endotoxin levels were respectively, for glass and steel containers, 4.78 ± 0.07 and 4.87 ± 0.03. DISCUSSION AND CONCLUSION: The present validation study confirms the effectiveness of treatment with dry heat for sterilization and depyrogenation of glass and steel containers. This method of sterilization and depyrogenation meets the microbiological quality requirements for the preparation of MNP.

[Accuracy, precision and speed of parenteral nutrition admixture bags manufacturing: comparison between automated and manual methods]. / Exactitude, précision et rapidité de fabrication des poches de mélanges nutritifs parentéraux: comparaison de techniques automatisée et manuelle.

INTRODUCTION: The parenteral nutrition admixture (PNA) manufacturing in hospital pharmacy is realized by aseptic transfer (AT) or sterilizing filtration (SF). The development of filling systems for PNA manufacturing requires, without standard, an evaluation comparing to traditional methods of SF. MATERIALS AND METHODS: The filling accuracy of automated AT and SF was evaluated by mass and physical-chemistry tests in repeatability conditions (identical composition of PNA; n=five bags) and reproducibility conditions (different composition of PNA; n=57 bags). For each manufacturing method, the filling precision and the average time for PNA bags manufacturing were evaluated starting from an identical composition and volume PNA (n=five trials). RESULTS: Both manufacturing methods did not show significant difference of accuracy. Precision of both methods was lower than limits generally admitted for acceptability of mass and physical-chemistry tests. However, the manufacturing time for SF was superior (five different binary admixtures in five bags) or inferior (one identical binary admixture in five bags) to time recorded for automated AT. DISCUSSION AND CONCLUSIONS: We show that serial manufacturing of PNA bags by SF with identical composition is faster than automated AT. Nevertheless, automated AT is faster than SF in variable composition of PNA. The manufacturing method choice will be motivate by the nature (i. e., variable composition or not) of the manufactured bags.

Oral drug dosage forms administered to hospitalized children: Analysis of 117,665 oral administrations in a French paediatric hospital over a 1-year period.

Selecting the most appropriate dosage form, that ensures safe administration and adherence of medications, is a major issue for children. Marketed drugs, however, have rarely been tested for their use in children. There is a need for more data on drug formulations administered to children to identify unmet needs, and drive future paediatric research. We observed, over a 12-month follow-up, 117,665 oral drug administrations to 1998 hospitalized children. Nine-tenths belonged to five Anatomical Therapeutic Chemical classes: Alimentary tract & metabolism, Nervous system, Cardiovascular system, Anti-infectives for systemic use and Blood & blood forming organs, one third of drug doses administered to school-age children and adolescents were liquids, and extemporaneous capsules were commonly used in younger children. Our study shows that despite the advantages of solid dosage forms and recent evidence from randomized controlled trials showing their acceptability in infants, they are seldom used in paediatric practice.

[Clinical, pharmacokinetic and therapeutic study of amikacin with single daily dose and in combination in neutropenic children with fever]. / Etude clinique, pharmacocinétique et thérapeutique de l'amikacine en dose unique journalière et en association chez l'enfant neutropénique fébrile.

BACKGROUND: The efficacy of single daily dose of amikacin has been recently demonstrated in neutropenic children with fever. POPULATION AND METHODS: Eighteen children aged 1 to 15 years were included in the study. All patients were febrile and granulocytopenic and had indwelling intravenous catheter. Amikacin was administered as a 30-minute intravenous infusion once daily (20 mg/kg on day 1, then 15 mg/kg) for 3 to 30 days; the patients received amikacin in combination with piperacillin and vancomycin. Serum levels of amikacin were measured on days 1, 3, 6 and 10, and 30 min, 60 min and 180 min after the end of the infusion. RESULTS: All patients responded favourably to the antibiotic therapy. Sixty-two kinetics were performed: peak amikacin concentrations measured (30 min after 30-min infusion) on day 1 averaged 43.7 micrograms/mL (+/- 13.8). A significant increase in peak serum concentrations was observed during the treatment (day 3 vs day 10) without change in the trough serum concentrations. The volumes of distribution were considerably important in these granulocytopenic children and there was a large inter and intra-patient variability; the elimination half-life of the amikacin was short (1.45 h). There was no significant nephrotoxicity in any patient. CONCLUSION: The use of single daily dose amikacin in combination with a broad spectrum beta-lactam antibiotic and vancomycin was efficient and safe in febrile granulocytopenic children. The simulation of the amikacin behaviour in the deep compartment should be evaluated; in fact, it might reflect better accumulation of the drug than serum concentrations.

[Contamination of ternary mixtures of parenteral nutrition by barium]. / Contamination des mélanges ternaires d'alimentation parentérale par le Baryum.

Patients treated with chronic parenteral nutrition develop metabolic bone diseases. Because of the chemical relationship between barium and calcium, and the barium bone affinity, a possible responsibility of this element in this bone pathology has been searched. The study of the different parenteral nutrition components shows that significant concentrations of barium have been found in total parenteral nutrition bags.

[Comparison of three ventilatory modes during immediate postoperative transfer of cardiac surgical patients]. / Comparaison de trois modes ventilatoires au cours du transport postopératoire immédiat du patient opéré de chirurgie cardiaque.

OBJECTIVE: Compare three ventilatory strategies during the immediate postoperative transfer of cardiac surgical patient. STUDY DESIGN: Prospective, comparative and observational study. PATIENTS AND METHODS: After approval by our local ethical committee, 330 patients undergoing on-pump cardiac surgery were consecutively included. Patients suffering from chronic obstructive pulmonary disease, exhibiting intraoperative hypoxemia or requiring nitric oxide were excluded. The ventilatory mode was left at the discretion of the anesthesiologist and included: controlled mechanical ventilation (FiO(2)=1, N=124) or (FiO(2)=0.6, N=106), and manual ventilation using rebreathing bag (N=100). A blood gas analysis was performed immediately prior to connecting patient at ventilator at the arrival in ICU. RESULTS: The mean duration of transfer was 3.9+/-1.4 min. Invasive pressure monitoring was used in all patients. The pulse oxymetry and electrocardiogram were respectively used in 78% and 24% of patients. PaO(2) values less than 100 mmHg and those more than 300 mmHg were more frequently found in patients ventilated by rebreathing bag (42%) and mechanical ventilation FiO(2)1 (52%), respectively. No significant difference was found between groups regarding PaCO(2) values. CONCLUSION: When rebreathing bag is used for transfer in ICU, severe decrease in PaO(2) may be observed. In absence of intraoperative hypoxemia, a mechanical ventilation with FiO(2)0.6 seems to be the most suitable ventilatory strategy for such short immediate postoperative transfer.

Prediction of future serum concentrations with Bayesian fitted pharmacokinetic models: results with data collected by nurses versus trained pharmacy residents.

Recording the times of dosage administration and serum sampling by trained personnel resulted in significantly greater adherence to the protocol of therapeutic drug monitoring and in significantly greater precision in the achievement of desired serum concentration goals of aminoglycoside therapy than when relatively untrained personnel recorded it as a comparatively unemphasized part of their job. This was true even when only data of peak and trough serum concentrations were used. This study demonstrates that thoughtful data collection by appropriately trained nursing, pharmacy, or other clinical personnel is an essential part of therapeutic drug monitoring and plays a significant role in the optimal individualization of drug dosage regimens for patient care.

How many patients and blood levels are necessary for population pharmacokinetic analysis? A study of a one compartment model applied to cyclosporine.

OBJECTIVE: This paper describes a method to determine the number of patients and the number of blood levels which are appropriate for a pharmacokinetic population analysis. METHODS: We studied this question by performing 203 runs of population analysis, using the NPEM algorithm with a one compartment model, starting with only one patient and only one blood level, then 2 patients with one blood level each, until reaching 38 patients each with 5 blood levels. Data were obtained from liver transplant patients treated with cyclosporine. RESULTS: For 2, 3, 4 or 5 blood levels, the values of median clearance (CL) converged and became almost equal after about 10 patients were studied. The value then remained stable and the variation was fairly small. With only one blood level per patient, the variation was greater. In contrast, with one blood level, median CL became similar to groups having 2, 3, and 4 blood levels only after about 35 patients had been studied, versus about 10. Similar results were found for the median values of the volume of distribution (V). For a one compartment model with parameters of V and CL, from 15 to 20 patients with 2 blood levels may be enough to perform a reasonable population pharmacokinetic analysis; the values of the pharmacokinetic parameters were very similar to those obtained with 3 to 5 blood levels and with more patients. However, a subpopulation probably requires more patients and at least 4 or 5 blood levels per patient to be recognised. CONCLUSION: Examination of converging pharmacokinetic parameter values by stepwise increases in the number of patients and blood levels appears to be a pragmatic and empirical approach to determine the possible number of patients and blood levels required for population pharmacokinetic analysis.

[Evaluation of urinary calcium/creatinine ratio in premature and full-term newborn infants]. / Evaluation du rapport calcium/créatinine urinaire chez le nourrisson et le nouveau-né à terme et prématuré.

Urinary calcium/creatinine ratio (U Ca/creat) was studied in infants, term and preterm newborn babies. In 31 1.5-24 months old healthy infants, the median U Ca/creat was 0.16 mmol/mmol (range 0.013-1.17) and was similar to the value obtained in children older than 4 years. In 55 healthy full-term newborns studied in the first week of life, the median U Ca/creat was 0.12 mmol/mmol. However the range of values was extremely wide (0.0006-4.75), suggesting that the U Ca/creat ratio is of little interest to screen for hypercalciuria during the neonatal period. In 31 premature newborns, the median U Ca/creat was 1.08 mmol/mmol, a value significantly higher than in the two other groups (P < 0.001); as in the term newborns there was a very wide range of values (0.057-6.83). However after excluding the premature babies with elevated serum 25 OHD level, this difference was not statistically significant.

Continuous infusion of high-dose cisplatin in children: pharmacokinetics of free and total platinum.

A pharmacokinetic study was carried out in two infants and two (older) children with high-dose cisplatin (CP) (40 mg/m2/day) by 5-day continuous infusion. Following interruption of the infusion, the decrease in total plasma platinum was biphasic, with a terminal half-life of 155.5-418 h. During administration the urinary concentrations were between 7.66 and 15.2 mg/l. Thirty to thirty five per cent of the administered dose was eliminated within 48 h of discontinuing infusion. Free platinum (FP) levels declined in a biphasic manner, with a mean (+/- S.E.) elimination half-life of 81.25 (+/- 34.9) h. FP was still detectable in the plasma 10 days after the end of infusion with levels above 0.010 micrograms/ml. FP availability, measured as the area under the curves (AUC) of the FP concentration--up to 2 h after ending the infusion--were 768 (+/- 326) micrograms.min/ml. Inter- or intra-individual differences in AUC values were not observed.

A population pharmacokinetic model of cyclosporine in the early postoperative phase in patients with liver transplants, and its predictive performance with Bayesian fitting.

The availability of personal computer programs to individualize drug regimens has stimulated interest in modeling population pharmacokinetics. This study used the NPEM2 software to determine cyclosporine population pharmacokinetic parameter values and distributions in a first group of 25 recipients of liver transplants during their first postoperative week. On a second group of 25 patients, the authors used these values to evaluate Bayesian predictive performance of cyclosporine blood concentrations with the USC*PACK PC program. During the study period, all the patients have been treated by continuous intravenous infusion. The one-compartment model pharmacokinetic parameter-the slope of volume to body weight (Vs) and the elimination rate constant (Kel) values found (mean values: Vs = 2.177 l/kg, Kel = 0.235 h(-1); median values: Vs = 1.559 l/kg, Kel = 0.163 h(-1); the percent coefficient of variation (Vs = 92%, Kel = 79%) appear reasonable and show the ability of NPEM2 to deal with sparse data. When the predictions were studied with day 1, day 2, or day 3 concentrations, predictive bias was respectively -0.030, -0.013, and 0.013 microg/ml, suggesting a greater clearance of cyclosporine immediately after surgery, the clearance decreasing in the days after. With the first three blood levels and the Bayesian fitting procedure, it was possible to predict at least half the subsequent measured blood levels of each patient accurately (within 20%) in more than three-quarters (76%) of the second group of recipients of transplants, and for 40% of patients the authors obtained accurate predictions in 100% of the subsequent blood levels. For a few patients (12%) they found quite poor predictions. The reason for this is unclear. The results suggest that this population model and the Bayesian fitting procedure using two or three blood levels can be reasonably and carefully used to control, in real time, cyclosporine blood levels in a majority of new patients with liver transplants.