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ObjectivesThis study aimed to monitor the contamination by antineoplastic drugs on work surfaces in a compounding unit 4 years after its implementation.MethodsThis descriptive study was done in a unit performing on average 45 000 preparations per year. Surface sampling points (N=23) were monitored monthly in the frame of routine activity from the opening of an anticancer drug compounding unit. Contamination with nine antineoplastic drugs (cyclophosphamide, ifosfamide, dacarbazine, 5-fluorouracil, methotrexate, gemcitabine, cytarabine, irinotecan and doxorubicin) was assessed on wipes with a local liquid chromatography coupled with a tandem mass spectrometer analysis. The contamination rate (CR, %) was prospectively monitored every month during the entire study period. The occurrence of critical incidents was also registered. The effect of each safety measure implemented during this period was also analysed.ResultsBased on the 1104 samples collected between March 2016 and March 2020, the CR was 18.5%. If three different critical incidents among a vial breakage that occurred were individually considered, this CR was slightly lower than that in the literature. Eight months after opening and taking different corrective actions, the overall CR dropped from 42.39% to 11.52% (p+sampling points.ConclusionsFrom the beginning of the study and from month to month, surface contamination was limited to the nearest sampling points to the compounding unit. This 4-year monitoring study allowed us to determine the intravenous conventional antineoplastic drugs and sampling points to be focused on.

The aim of this work was to develop a filtering biocidal polypropylene (PP) nonwoven textile structure to block and inactivate airborne bacteria and viruses.

International audience; BackgroundThe optimal dose of tranexamic acid to inhibit hyperfibrinolysis in postpartum haemorrhage is unclear. Tranexamic Acid to Reduce Blood Loss in Hemorrhagic Cesarean Delivery (TRACES) was a double-blind, placebo-controlled, randomised, multicentre dose-ranging study to determine the dose–effect relationship for two regimens of intravenous tranexamic acid vs placebo.MethodsWomen experiencing postpartum haemorrhage during Caesarean delivery were randomised to receive placebo (n=60), tranexamic acid 0.5 g (n=57), or tranexamic acid 1 g i.v. (n=58). Biomarkers of fibrinolytic activation were assayed at five time points, with inhibition of hyperfibrinolysis defined as reductions in the increase over baseline in D-dimer and plasmin–antiplasmin levels and in the plasmin peak time.ResultsIn the placebo group, hyperfibrinolysis was evidenced by a mean increase over baseline [95% confidence interval] of 93% [68–118] for D-dimer level at 120 min and 56% [25–87] for the plasmin–antiplasmin level at 30 min. A dose of tranexamic acid 1 g was associated with smaller increases over baseline (D-dimers: 38% [13–63] [P=0.003 vs placebo]; plasmin–antiplasmin: –2% [–32 to 28] [P=0.009 vs placebo]). A dose of tranexamic acid 0.5 g was less potent, with non-significant reductions (D-dimers: 58% [32–84] [P=0.06 vs placebo]; plasmin–antiplasmin: 13% [18–43] [P=0.051]). Although both tranexamic acid doses reduced the plasmin peak, reduction in plasmin peak time was significant only for the 1 g dose of tranexamic acid.ConclusionsFibrinolytic activation was significantly inhibited by a dose of intravenous tranexamic acid 1 g but not 0.5 g. Pharmacokinetic–pharmacodynamic modelling of these data might identify the best pharmacodynamic monitoring criteria and the optimal tranexamic acid dosing regimen for treatment of postpartum haemorrhage.

Background Prostate cancer is one of the most common forms of cancer in men. An imaging technique for its diagnosis is [68Ga]-prostate specific membrane antigen (68Ga-PSMA-11) positron emission tomography (PET). Gallium 68 (68Ga) is typically obtained using a germanium 68/gallium 68 (68Ge/68Ga) generator, allowing for the diagnostic drug to be made readily available in the nuclear medicine department through elution. To meet the increasing demand for 68Ga labeled peptides and to reduce the cost of radiosynthesis, it is therefore necessary to optimize the elution process of 68Ge/68Ga generators. This study aims to identify the most effective approach for optimizing radiosynthesis using double elution in parallel of two 68Ge/68Ga generators. Two methods have been tested: one using prepurification, and the other using fractionated elution. Results Five synthesis sequences were conducted using each method. The mean labeling yields for double elution with prepurification were 45.8 ± 29.4 (mean ± standard deviation) and none met the required criteria. The mean labeling yields for the fractionated double elution were 97.5 ± 1.9 (mean ± standard deviation) meeting the criteria, significantly superior to the prepurification method (p=0.012), and similar to those of simple elution. There was no significant difference in the elution yields of both methods. Conclusions This study showed that fractionated double elution from 68Ge/68Ga generators produced a significantly higher labeling yield than double elution with prepurification, resulting in a larger activity recovered by radiosynthesis, and thereby allowing for more diagnostic tests to be performed. Additionally, this method does not add complexity or synthesis time compared to simple elution labeling, and could also be applied to other 68Ga labeled peptides.

Resume Objectifs Mener une intervention ergonomique en suivant la methodologie de l’analyse de l’activite du processus de formations des internes en pharmacie clinique a l’analyse des prescriptions. Methodes L’evaluation a ete realisee sur deux semestres : de mai a octobre 2016 (premiere etude) et de novembre 2016 a avril 2017 (deuxieme etude). Les entretiens et observations ont ete effectues par une ergonome experte dans ce type d’evaluation. La premiere etude reposait sur des observations du dispositif de formation et des entretiens a plusieurs temps. La deuxieme etude a permis d’accompagner les pharmaciens et d’evaluer les changements suite aux recommandations de la precedente etude. Resultats Six et neuf internes ont participe respectivement a la premiere et deuxieme etude. Au cours de la premiere etude, 6 difficultes ont ete remontees permettant la prise de decisions d’implementation et dont le suivi a ete realise au cours de la deuxieme etude. Les retours des internes etaient globalement positifs pour la formation a la prise de fonctions, mais negatif pour l’etape de qualification. Le nombre moyen de craintes exprimees par les internes etait plus eleve en debut (2,9 ± 0,9 craintes) qu’en fin de stage (1 ± 0,7 crainte). Conclusions Le dispositif de formation a ete adapte aux attentes et ressentis des internes. Les suivis en debut et tout au long du stage des internes etaient primordiaux. La prochaine etape sera d’evaluer l’apport des tableaux de bord de suivi des competences en pharmacie clinique mis en place dans le nouveau diplome d’etudes specialisees de pharmacie hospitaliere.

Background Defibrotide is indicated for patients who develop severe sinusoidal obstructive syndrome following allogeneic hematopoietic cell transplantation (allo-HCT). Preclinical data suggested that defibrotide carries a prophylactic effect against acute graft-versus-host disease (aGVHD). Objective The purpose of this study was to investigate the effect of defibrotide on the incidence and severity of aGVHD. Methods This single-center retrospective study included all consecutive transplanted patients between January 2014 and December 2018. A propensity score based on 10 predefined confounders was used to estimate the effect of defibrotide on aGVHD via inverse probability of treatment weighting (IPTW). Results Of the 482 included patients, 64 received defibrotide (defibrotide group) and 418 did not (control group). Regarding main patient characteristics and transplantation modalities, the two groups were comparable, except for a predominance of men in the defibrotide group. The median age was 55 years (interquartile range [IQR]: 40-62). Patients received allo-HCT from HLA-matched related donor (28.6%), HLA-matched unrelated donor (50.8%), haplo-identical donor (13.4%), or mismatched unrelated donor (7.0%). Stem cell source was either bone marrow (49.6%) or peripheral blood (50.4%). After using IPTW, exposure to defibrotide was not significantly associated with occurrence of aGVHD (HR = 0.97; 95% CI 0.62-1.52; P = .9) or occurrence of severe aGVHD (HR = 1.89, 95% CI: 0.98-3.66; P = .058). Conclusion and Relevance Defibrotide does not seem to have a protective effect on aGVHD in patients undergoing allo-HCT. Based on what has been reported to date and on these results, defibrotide should not be considered for the prevention of aGVHD outside clinical trials.

International audience; In the last decades, tranexamic acid (TXA) has emerged as an essential tool in blood loss management in obstetrics. TXA prophylaxis for postpartum haemorrhage (PPH) has been studied in double-blind, placebo-controlled, randomized clinical trials (RCTs). Given the small observed preventive effect, the systematic use of TXA for vaginal and/or caesarean deliveries remains controversial. The result of a pharmacokinetic modelling suggests that relative to intravenous administration, intramuscular administration may be an equally effective alternative route for preventing PPH and may enable access to this drug in low-resource countries. Prophylaxis is currently studied in high-risk populations, such as women with prepartum anaemia or placenta previa.TXA effectively reduces blood loss and PPH-related morbidity and mortality during active PPH, as demonstrated by high-grade evidence from large RCTs. The drug has a good safety profile: in most cases, only mild gastrointestinal or visual adverse events may be observed. TXA use does not increase the risk of serious adverse events, such as venous or arterial thromboembolism, seizures, or acute kidney injury. The TRACES in vivo analysis of biomarkers of TXA’s antifibrinolytic effect have suggested that a dose of at least 1 g is required for the treatment of PPH. The TRACES pharmacokinetic model suggests that because TXA can be lost in the haemorrhaged blood, a second dose should be administered if the PPH continues or if severe coagulopathy occurs. Future pharmacodynamic analyses will focus on the appropriateness of TXA dosing regimens with regard to the intensity of fibrinolysis in catastrophic obstetric events.

Chemotherapy preparations are often complex and subject to a strict regulatory context. The existing control methods are often limited to Double Visual Control (DVC). In this paper, the preparation circuit of chemotherapy drugs is evaluated through data collection and statistical analysis in order to highlight the difficulties encountered. The results regarding preparation and control times and the number of task interruptions highlight the unreliability of the DVC and its impact on processing time. As a solution, we propose a decision support system "Smart Prep" based on Augmented Reality (AR), co-developed, and commercialized by the Faculty of Pharmacy of Lille, Ecole Centrale de Lille and the company Computer Engineering. This system allows the preparation of chemotherapy drugs according to a step-by-step mode, a traceability of the preparation steps and a reduction of tasks' interruptions.

Chemotherapy preparations are often complex and subject to a strict regulatory context. The existing control methods are often limited to Double Visual Control (DVC). In this paper, the preparation circuit of chemotherapy drugs is evaluated through data collection and statistical analysis in order to highlight the difficulties encountered. The results regarding preparation and control times and the number of task interruptions highlight the unreliability of the DVC and its impact on processing time. As a solution, we propose a decision support system “Smart Prep” based on Augmented Reality (AR), co-developed, and commercialized by the Faculty of Pharmacy of Lille, Ecole Centrale de Lille and the company Computer Engineering. This system allows the preparation of chemotherapy drugs according to a step-by-step mode, a traceability of the preparation steps and a reduction of tasks’ interruptions.

Objective Dobutamine is an inotropic agent given to patients with low cardiac output or undergoing cardiac surgery in intensive care units. Routine clinical care protocols recommend a target dilution concentration of 10 mg/mL dobutamine from the 250 mg/20 mL commercial solution. This study aimed to assess the 1-year stability of ready-to-use 10 mg/mL diluted dobutamine solutions. Two types of 50 mL conditioning, polypropylene (PP) syringes or cyclic-oleofin-copolymer (COC) vials and two diluents (5% dextrose (D5W) and normal saline (NS)) were tested. Methods Reversed-phase liquid chromatography coupled with an ultraviolet detection stability-indicating method was developed for dobutamine and validated according to selectivity, linearity, sensitivity, accuracy and precision. Chemical stability was considered to have been maintained if the measured concentrations were >90% of the initial concentration with no colour change. Physical stability was assessed through sterility tests, pH and osmolality monitoring, and subvisible particle counting. Containers were stored at −20±5°C, +5±3°C and +25±2°C with 60%±5% relative humidity in a dark, closed environment. Results According to this study, the physicochemical stability of 10 mg/mL dobutamine solutions prepared with D5W or NS is constant throughout a 365-day period when stored in COC vials, at all the aforementioned temperatures, whereas solutions in PP syringes required a refrigerated temperature and should not be administered after 21 days or 3 months when prepared with D5W or NS, respectively, or after 1 month at ambient temperature whatever the diluent. Conclusion Our results argue in favour of adopting the compounding of ready-to-use 10 mg/mL dobutamine solutions in COC vials in centralised intravenous additive services.

Management of chemotherapies is a strategic issue for european healthcare. Dose-banding enables to reduce waiting time of patients in day care units and drug wastage. The aim of this study was to assess the stability of 5-Fluorouracile (5-FU) at standardised rounded doses of 4 and 5 g in MyFuser® portable infusion pump for in-advance preparation. Ten MyFuser® (4 and 5 gr 5-FU added to NaCl 0.9%) were prepared under aseptic conditions and stored at room temperature (23 ± 2 °C) for 28 days then at 30 °C for three days. Physical stability tests were periodically performed: visual and microscopic inspection, pH measurements and optical densities. The concentration of solutions was measured by High Performance Liquid Chromatography/UV detector. Results confirm the stability of 5-FU at selected SRD of 4 g and 5 g with NaCl 0.9% in MyFuser® for at least 28 days at room temperature and three days at 30 °C, allowing in-advance preparation.

OBJECTIVES: The objectives were to compare clinical pharmacist interventions between two care groups: COVID-19-positive and COVID-19-negative patients, and to identify drugs that require particular attention, especially those involved in COVID-19 management. METHODS: A prospective cohort study was conducted on patients with positive and negative COVID-19 statuses admitted to Lille University Hospital over 1 month. Pharmaceutical analysis instigated interventions to rectify drug-related errors. For each pharmaceutical intervention (PI), the anatomical therapeutic chemical classification of the drug and the outcome of such an intervention were specified. RESULTS: The study included 438 patients. Prescription analysis led to 188 PIs performed on 118 patients (64 COVID-19-positive patients and 54 COVID-19-negative patients). Most drug-related problems were incorrect dosage representing 36.7% (69/188) of all interventions: 27.9% (29/104) for the COVID-19-positive group and 47.6% (40/84) for the COVID-19-negative group. The most frequent PI in 34% (64/188) of cases was terminating a drug: 27.9% (29/104) for the COVID-19-positive group and 47.6% (40/84) for the COVID-19-negative group. The main drug classes involved were antithrombotic agents (20.7%, 39/188), antibacterials for systemic use (13.8%, 26/188) and drugs for gastric acid-related disorders (6.4%, 12/188). Study population was limited to a single centre over 1 month. CONCLUSION: No difference in PI was noted between the two groups. The presence of pharmacists led to a reduction in drug-related prescription problems, especially for antithrombotic and antibacterial drugs for both groups. Clinical pharmacy commitment in such a pandemic is therefore important.

Gemcitabine is an analogue of cytidine arabinoside, used alone or in combination chemotherapy to treat various type of cancer. The dose-banding of gemcitabine provides the opportunity to anticipate the preparation of this anticancer drug on condition of carrying out stability studies. The aim of this study is to develop and validate a stability-indicating ultra-high-performance Liquid Chromatography (UHPLC) method for measuring the concentration of gemcitabine and to evaluate its stability at standardised rounded doses in polyolefin bags. The UHPLC with photodiode array (PDA) detector method was developed and validated (linearity, precision, accuracy, limits of detection and quantification, robustness and degradation test). Thirty polyolefin bags of gemcitabine (1600 mg/292 ml (n = 10), 1800 mg/297 ml (n = 10) and 2000 mg/303 ml (n = 10)) were prepared under aseptic conditions and stored at 5 ± 3 °C and 23 ± 2 °C for 49 days. Physical stability tests were periodically performed: visual and microscopic inspection and optical densities. The chemical stability was evaluated through pH monitoring and chromatographic assays. The results confirm the stability of Gemcitabine at selected standardised rounded doses of 1600 mg, 1800 mg and 2000 mg in NaCl 0.9% polyolefin bags for at least 49 days at 5 ± 3 °C and 23 ± 2 °C, allowing in-advance preparation.

Medication non-adherence (NA) after allogeneic hematopoietic cell transplantation (allo-HCT) can lead to serious complications. This study assesses NA in French adult and pediatric recipients and identifies factors associated with NA. In accordance with the EMERGE and STROBE guidelines, a cross sectional multicentric survey was conducted. We used a self-reported questionnaire that was adapted to adults and pediatrics and that could provide a picture of all three phases of medication adherence: initiation, implementation, persistence. We enrolled 242 patients, 203 adults (mean age: 51 years old, 50.7% male) and 39 children (mean age: 9 years old, 56.4% female). Reported NA was estimated at about 75% in both populations, adults and pediatrics. In adults, the univariate analysis showed that patients less than 50 years old (P = 0.041), (i) treated with cyclosporine (P = 0.02), (ii) treated with valacyclovir/acyclovir (P = 0.016), and (iii) experiencing side effects (P = 0.009), were significantly more non-adherent. In multivariate analysis, only recipient age was significantly associated to NA (P = 0.05). The limited size of the pediatric population did not allow us to draw any statistical conclusion about this population. To the best of our knowledge, this is the first study in France on NA in allo-HCT recipients. Our results highlight the age factor as the only factor related to NA. Further studies are needed to confirm our observations and refine results in pediatric populations, currently most at risk of medication NA.

Errors in injectable preparations with high-risk drugs can be fatal. This study aimed to identify the factors influencing the accuracy of high-risk injectable drug concentrations in appliances used for intensive care unit preparation practices. Norepinephrine (NE) was chosen as an example of a high-risk medication drug. The concentration (0.2 and 0.5 mg/mL), the diluent (sodium chloride 0.9% and 5% dextrose), and the container type (prefilled- and empty-infusion bag and syringe) were tested as potential variability factors. An ultraviolet spectrophotometric method was used for NE dosage. 108 NE solutions were prepared by five individuals (pharmacists or laboratory technicians) with clinical experience as well as experience in the aseptic preparation of solutions. The container type was found to be the only factor influencing the accuracy of NE concentration. NE solutions in syringes proved to be the most accurate while preparations in prefilled bags tended to underdose NE.

Purpose Midazolam is a benzodiazepine derivative commonly used in intensive care units to control sedation. Its use requires dilution of a 5-mg/mL commercial solution to a target concentration of 1 mg/mL. A study was conducted to evaluate the stability of diluted ready-to-use 1-mg/mL midazolam solutions over 365 days when stored in cyclic olefin copolymer vials or polypropylene syringes. Methods A specific stability-indicating high-performance liquid chromatography coupled with UV detection method was developed for midazolam hydrochloride and validated for selectivity, linearity, sensitivity, precision, and accuracy. Three storage conditions were tested: –20°C ± 5°C, 5°C ± 3°C, and 25°C ± 2°C at 60% ± 5% relative humidity. Half of the vials were stored upside down to test for the absence of interaction between midazolam and the stopper. Particle contamination, sterility, and pH were assessed. Results The limit of stability was set at 90% of the initial concentration. After 1 year’s storage at –20°C and 5°C, concentrations remained superior to 90% under all storage conditions. At 25°C, stability was maintained up to day 90 in syringes (mean [SD], 92.71% [1.43%]) and to day 180 in upright and upside-down vials (92.12% [0.15%] and 91.57% [0.15%], respectively). No degradation products were apparent, no variations in pH values were detected, and containers retained their sterility and conformity with regard to any specific contamination during the study. Conclusion The evaluated 1-mg/mL midazolam solution was stable over a 1-year period when stored at a refrigerated (5°C) or frozen (–20°C) temperature in both vials and syringes; with storage at 25°C, the stability duration was lower. The preparation of ready-to-use midazolam solutions by a hospital pharmacy is compatible with clinical practice and could help to decrease risks inherent in dilution in care units.

An important amount of cytotoxic drug may accumulate in the workplace following the breakage of a vial containing an anticancer drug. Thanks to the monthly monitoring of the surface contamination in our compounding unit, a strong increase of cyclophosphamide contamination was highlighted in the storage area following the breakage of the vial, despite application of the emergency procedure. This study presents an analysis of chemical decontamination in the context of massive contamination. Samples were taken on the floor and on the caster of a storage shelf where the vial broke. The residual contamination was measured with a liquid chromatography–mass spectrometry/mass spectrometry method. An admixture of 10−2 M sodium dodecyl sulfate and 70% isopropanol (SDS/IPA 8:2) was selected as the decontamination solution. High amounts of cyclophosphamide were retrieved. The initial contamination on the floor was over 20 ng/cm2. Three decontaminations with SDS/IPA were carried out at Day 61, Day 68, and Day 71. The amount of cyclophosphamide decreased to 0.45 ng/cm2 at D134. However, high values were still measured on the caster despite successive decontaminations, with a maximal value of 19.78 ng/cm2 observed at Day 106. Continuous monitoring in our unit led us to highlight the inefficiency of our emergency procedure to eliminate high cyclophosphamide contamination. The procedure involving the SDS/IPA admixture was more efficient on the floor compared to the caster, which is a different surface type and porosity. This work highlights the importance of improving the procedures of incident management using contamination monitoring and repeated decontamination procedures adapted to different contaminants and surfaces.

Objectives Norepinephrine is a vasopressor frequently administered after dilution to treat hypotension and shocks in intensive care units. The stability of norepinephrine is known to be highly sensitive to storage conditions. Moreover, medication errors linked to the dilution step are frequent and may be deleterious for critically-ill patients, especially in intensive care units. This study aimed to evaluate the stability of ready-to-use diluted norepinephrine solutions prepared at two target concentrations (0.2 and 0.5 mg/mL), according to the summary of product characteristics, and stored for 365 days in two containers: AT-closed cyclic olefin copolymer vials, and polypropylene syringes. Methods A fast reversed-phase liquid chromatography method coupled with an ultra-violet detector was developed to assess the chemical stability of norepinephrine solutions. Validation was conducted according to the linearity of the calibration ranges, selectivity, sensitivity, accuracy and precision. Dosage, sub-visible particle contamination, pH monitoring and sterility assays were performed. Chemical stability was maintained if the measured concentration respected the lower limit of 90% of the initial concentration. Containers were stored at −20±5°C, +5±3°C and +25±2°C with 60±5% relative humidity in a dark closed enclosure. Results Stability was successfully maintained for every concentration and container tested when stored at −20±5°C and +5±3°C. In these storage conditions, particle contamination, pH monitoring and sterility assay respected the required criteria. Chemical degradation and colouring of solutions appeared before the end of the 1 year study period for most norepinephrine solutions stored at room temperature. Conclusions Ready-to-use solutions containing 0.2 and 0.5 mg/mL norepinephrine in polypropylene syringes or cyclic olefin copolymer vials must be stored at refrigerated or frozen temperatures to obtain acceptable 1 year shelf-stability. Exposure to higher temperatures significantly decreases shelf-stability. Our study protocol for compounding polypropylene syringes and cyclic olefin copolymer vials containing norepinephrine is adapted to implementation in centralised intravenous additive services.

Vancomycin hydrochloride is an antibiotic belonging to the glycopeptide family and acts by inhibiting the synthesis of the peptidoglycan wall. This antibiotic is active against Gram-positive aerobic and anaerobic bacteria1 2 and is commonly used in hospitals to treat serious infections.3 4 Vancomycin has slow bactericidal time-dependent activity and can be administered by continuous or intermittent intravenous infusion. In France, administering vancomycin by continuous infusion over 24 hours is recommended.5 6 The Summary of Product Characteristics (SmPC) recommends reconstituting a 1 g vial with 20 mL of water for injection (WFI), then diluting it in 100 mL of saline solution. The amount of vancomycin to treat an adult infection is superior to 1 g and so the volume administered can be higher than 100 mL. This volume must be limited in children or in patients on water restriction, such as those suffering from hyponatraemia and cardiovascular diseases or are in intensive care.7 Some studies on vancomycin stability have already been performed. Solutions at 5 and 10 mg/mL were stable for 58 days at +4°C in 100 mL polyvinyl chloride (PVC) infusion bags with no specification with regard to protection from light.8 Vancomycin was stable at 5 mg/mL in PVC bags for 48 hours at +22°C without protection from light and for 7 days at +4°C with protection from light.9 Raverdy et al 10 examined the stability of vancomycin diluted in 5% dextrose at high concentration (83 mg/mL) and was stable for 72 hours at +37°C. However, none of these studies reflects real infusion conditions as vancomycin is usually administered at 30 mg/kg/day.11 12 In practice, clinical services infuse vancomycin into electric syringe pumps using 50 mL (for adults) or 20 mL (for children) syringes. No stability study has yet been performed for such concentrations, in 50 or 20 mL syringes, at room temperature, nor has the reconstitution procedure13 been …

The aim of this study was to evaluate the population pharmacokinetics of tranexamic acid (TXA) administered intravenously at a single dose of 0.5 or 1 g in parturients undergoing active hemorrhagic cesarean delivery and to evaluate the influence of patient variables on TXA pharmacokinetics. Subjects from three recruiting centers were included in this PK sub-study if randomized in the experimental group (i.v TXA 0.5 g or 1 g over one minute) of the TRACES study. Blood samples and two urinary samples were collected within 6 h after TXA injection. Parametric non-linear mixed-effect modeling (Monolix v2020R1) was computed. The final covariate model building used 315 blood and 117 urinary concentrations from seventy-nine patients. A two-compartment model with a double first-order elimination from the central compartment best described the data. The population estimates of clearance (CL), central volume of distribution (V1), and half-life for a typical 70 kg patient with an estimated renal clearance of 150 mL/min (Cockroft–Gault) were 0.14 L/h, 9.25 L, and 1.8 h. A correlation between estimated creatinine clearance and CL, body weight before pregnancy, and V1 was found and partly explained the PK variability. The final model was internally validated using a 500-run bootstrap. The first population pharmacokinetic model of TXA in active hemorrhagic caesarean section was successfully developed and internally validated.

Purpose This study evaluated the stability of diluted insulin aspart solutions (containing insulin aspart and preservatives) at their most commonly used concentration in intensive care units (1 unit/mL), in 2 container types: cyclic olefin copolymer (COC) vials and polypropylene (PP) syringes. Methods Insulin aspart solution (1 unit/mL, diluted in 0.9% sodium chloride injection) was stored for 365 days in COC vials with gray stoppers and PP syringes at refrigerated (5°C ± 3°C) and ambient temperatures (25°C ± 2°C at 60% ± 5% relative humidity and protected from light). Chemical testing was conducted monthly using a validated high-performance liquid chromatography method (quantification of insulin aspart, phenol, and metacresol). Physical stability was evaluated monthly via pH measurements, visible and subvisible particle counts, and osmolality measurements. Sterility testing was also performed to validate the sterile preparation process and the maintenance of sterility throughout the study. Results The limit of stability was set at 90% of the initial concentrations of insulin aspart, phenol, and metacresol. The physicochemical stability of 1-unit/mL insulin solutions stored refrigerated and protected from light, was unchanged in COC vials for the 365-day period and for 1 month in PP syringes. At ambient temperature, subvisible particulate contamination as well as the chemical stability of insulin and metacresol were acceptable for only 1 month’s storage in PP syringes, while insulin chemical stability was maintained for only 3 months’ storage in COC vials. Conclusion According to our results, it is not recommended to administer 1-unit/mL pharmacy-diluted insulin solutions after 3 months’ storage in COC vials at ambient temperature or after 1 month in PP syringes at ambient temperature. The findings support storage of 1-unit/mL insulin aspart solution in COC vials at refrigerated temperature as the best option over the long term. Sterility was maintained in every condition. Both sterility and physicochemical stability are essential to authorize the administration of a parenteral insulin solution.

Introduction Healthcare workers are exposed to hazardous drugs such as antineoplastic drugs, which have potential carcinogenic, mutagenic and teratogenic effects. Protective measures must be taken after appropriate staff training to handle antineoplastic drugs in a safe way. The objective was to assess perception, knowledge, practices and training regarding the risk of exposure of healthcare workers in three French compounding units. Methods This descriptive study was based on a questionnaire made of 33 questions divided into five sections related to the handling of antineoplastic drugs: perception of the risks, knowledge of the risks, protection practices, specific training and general questions. Results Among the 39 participants, over half considered their overall risk of exposure to antineoplastic drugs not being very low. Inhalation was known to 69.2% of them as possible route of contamination. The breakroom was identified by 28.9% of them as a place of contamination. The procedure in case of accidental exposure to antineoplastic drugs was known by 69.2%, but only half could explain it. Only 38.5% said they changed their gloves every 30 min as recommended. Barely half said that they had been trained specifically for the handling of antineoplastic drugs during an initial training. Over half wished to be informed, trained and aware of the proper handling of antineoplastic drugs. Conclusion Although some of these results are encouraging, specifically when compared to the other settings where antineoplastic drugs are handled, there is still room for improvement. Efforts to build an adapted and impactful training program must pursue. Clinical trial registration Study CONTACT, ref. 19-504.

Background Chemotherapy doses are usually prescribed on the basis of body surface area but dose banding is emerging as an efficient alternative. Dose banding presents the possibility of in-advance preparation in a Centralized Intravenous Admixture Service. Aim of the study To evaluate the long-term stability of 5-fluorouracil at banded doses (700 mg and 800 mg) in polyolefin bags. Materials and methods Ten polyolefin bags were prepared under aseptic conditions and stored at 23 ± 2°C for 24 days. Five of them were composed of 14 mL 5-fluorocuracil (700 g) in 100 mL 0.9% sodium chloride solution and the five other of 16 mL 5-fluorouracil (800 mg) in 100 mL 0.9% sodium chloride solution. At defined times, physical stability parameters were assessed: optical densities, pH measurements, visual and microscopical inspections. Solutions concentrations were measured using high-performance liquid chromatography coupled with a photodiode array detector. Results No change was observed on pH and optical density measurements during the study period. Visual and microscopical inspections remained free of colour change, precipitate, microagregate or crystal. The concentrations of 5-Fluorouracil in 800 mg bags remained stable for 24 days while the concentration in 700 mg bags showed a stability of at least 17 days. Conclusion Five-fluorouracil at banded doses of 700 and 800 mg in polyolefin bags is physicochemically stable for at least 17 days at 23 ± 2°C. These results support the possibility of in advance centralised preparation.

Resume Objectifs Evaluer les connaissances et perceptions des pharmaciens et internes en pharmacie hospitaliere en France et au Quebec a propos des indicateurs de notoriete appliques en pharmacie. Identifier les determinants associes a ces connaissances. Methodes Il s’agit d’une etude descriptive transversale. Un questionnaire anonyme de 17 questions a ete elabore, publie sur le site de SurveyMonkey ( www.SurveyMonkey.com , SurveyMonkey, Portland, OR, EUA) et diffuse du 19 mars au 9 avril 2018. La proportion de repondants au Quebec et en France a ete comparee a l’aide d’un test de Chi2. Une valeur de p inferieure a 0,05 est consideree statistiquement significative. Resultats Un total de 899 pharmaciens et 147 internes a ete contacte par courriel. Le sondage a ete complete par 401 repondants (301-Quebec-taux de participation de 42 % ; 100-France-30 %). Globalement, 26 % (106/401) des repondants (67/301 au Quebec c. 39/100 France) ont declare avoir des connaissances ou de bonnes connaissances sur les indicateurs. Ces donnees sont corroborees par de nombreux autres resultats. Conclusion Une faible proportion de pharmaciens et internes en pharmacie hospitaliere connaissent les indicateurs de notoriete. Une bonne connaissance des indicateurs est notamment associee au fait d’exercer en France, dans un etablissement de sante universitaire ou de detenir des fonctions universitaires, d’avoir une experience professionnelle superieure a 10 ans, d’etre implique dans un projet de recherche, d’effectuer une veille electronique ou d’avoir un profil en ligne sur un moteur de recherche/base de donnees. Il apparait necessaire de mieux former les pharmaciens/internes en pharmacie sur les indicateurs de notoriete.

Although considerable efforts have been made over the last 40 years, occupational exposure to antineoplastic drugs is still a daily concern, since eradicating such contamination from workplaces seems unattainable. Considerable data are currently available on the risks associated with their use at work. Hospital facilities are often cleaned with marketed antimicrobials whose chemical decontamination efficacy certainly differs but remains unknown. To keep compounding facilities sterile, alcohol-based solutions are frequently used but with very limited efficiency. It would be particularly useful if a decontamination method could be added to the means already available so that all conventional antineoplastic drug contamination could be removed. Several degradation methods or desorption methods have previously been experimented, with varying success. They have never been compared or discussed in terms either of efficiency or usability. This review aims to analyse and discuss the results of each degradation or decontamination procedure and to compare them. This should facilitate selection of the method to be implemented in daily practice.

BACKGROUND: Transforming a drug from its commercial form into a ready-to-use drug is common practice, especially in pediatrics. However, the risk of compounding error is real and data on drug stability in practice are not always available. OBJECTIVE: The aim of this study was to assess, in real conditions, both the error rate and stability of three drugs: ketamine, remifentanil, and sufentanil. METHODS: A new rapid and easy-to-use high-performance liquid chromatography method with a diode array detector has been developed and validated to quantify these drugs and detect their degradation products. Over a 1-month period, 151 syringes were collected in the postanesthesia care unit. Seventy-three were stock solution syringes containing a 10-fold dilution of commercial drugs and 78 were serial dilution syringes made from successive dilutions of stock solutions. A comparison between real and expected concentrations as well as the detection of possible degradation products was carried out on these samples. RESULTS: All stock solution syringes had good chemical stability throughout the working day. A 4-µg/mL remifentanil serial dilution syringe, however, had to be discarded as a degradation peak was detected. Overall, 15.3% (95% CI, 9.5-21.1%) of syringes had a drug concentration outside the ±10% acceptability range, that is, 11.0% (95% CI, 3.7-18.2%) and 19.5% (95% CI, 10.6%-28.4%) of stock and diluted syringes respectively, with drug amounts ranging from -25.3% to 22.0%. The highest error rates were observed with sufentanil syringes: 20% and 28% for stock solution and serial dilution, respectively. CONCLUSIONS: The study shows that stock solution syringes prepared in advance are chemically stable throughout the day, unlike certain serial dilution syringes, indicating that the latter should be prepared just before administration to ensure chemical stability. Our results show that the error rate for serial dilution syringes is twice that of stock solution. Different safety measures are under discussion and have to be further studied.

In Clinical Decision Support System (CDSS), relevance of alerts is essential to limit alert fatigue and risk of overriding relevant alerts by health professionals. Detection of acute kidney injury (AKI) situations is of great importance in clinical practice and could improve quality of care. Nevertheless, to our knowledge, no explicit rule has been created to detect AKI situations in CDSS. The objective of the study was to implement an AKI detection rule based on KDIGO criteria in a CDSS and to optimize this rule to increase its relevance in clinical pharmacy use. Two explicit rules were implemented in a CDSS (basic AKI rule and improved AKI rule), based on KDIGO criteria. Only the improved rule was optimized by a group of experts during the two-month study period. The CDSS provided 1,125 alerts on AKI situations (i.e. 643 were triggered for the basic AKI rule and 482 for the improved AKI rule). As the study proceeds, the pharmaceutically and medically relevance of alerts from the improved AKI rule increased. A ten-fold increase was shown for the improved AKI rule compared to the basic AKI rule. The study highlights the usefulness of a multidisciplinary review to enhance explicit rules integrated in CDSS. The improved AKI is able to detect AKI situations and can improve workflow of health professionals.

In Clinical Decision Support System (CDSS), relevance of alerts is essential to limit alert fatigue and risk of overriding relevant alerts by health professionals. Detection of acute kidney injury (AKI) situations is of great importance in clinical practice and could improve quality of care. Nevertheless, to our knowledge, no explicit rule has been created to detect AKI situations in CDSS. The objective of the study was to implement an AKI detection rule based on KDIGO criteria in a CDSS and to optimize this rule to increase its relevance in clinical pharmacy use. Two explicit rules were implemented in a CDSS (basic AKI rule and improved AKI rule), based on KDIGO criteria. Only the improved rule was optimized by a group of experts during the two-month study period. The CDSS provided 1,125 alerts on AKI situations (i.e. 643 were triggered for the basic AKI rule and 482 for the improved AKI rule). As the study proceeds, the pharmaceutically and medically relevance of alerts from the improved AKI rule increased. A ten-fold increase was shown for the improved AKI rule compared to the basic AKI rule. The study highlights the usefulness of a multidisciplinary review to enhance explicit rules integrated in CDSS. The improved AKI is able to detect AKI situations and can improve workflow of health professionals.

Neonatal hyperglycaemia is frequent and requires insulin therapy. To resolve the difficulties encountered by paediatricians in stabilising glycaemia, the preparation and administration of insulin aspart were assessed and optimised. After high-performance liquid chromatography (HPLC-UV) assessment of insulin aspart preparations made according to the old protocol, a new protocol was drawn up. Dosage reliability of solutions prepared by paediatric nurses was evaluated by HPLC-UV. This new protocol was also tested in a Y-infusion situation and the need to saturate infusion tubes assessed. Wide deviations in insulin aspart concentrations were found between theoretical concentrations and preparations made according to the old protocol. Glycated insulin aspart was found in the majority of these preparations. The new protocol significantly reduced the variability of data and relative deviations around the target value. It also eliminated the formation of glycated insulin even in the case of co-infusion of parenteral nutrition and confirmed the need to saturate infusion tubes.Conclusion: The revision of the insulin therapy protocol reduced the variability of insulin concentration in preparations and avoided the administration of glycated derivatives potentially toxic for neonates. What is Known: • Insulin preparation in NICUs is a risky task because it is a two-step preparation • Diluted in dextrose, insulin aspart is unstable, with formation of potentially toxic glycated derivatives What is New: • This work proposes a new insulin therapy protocol validated by HPLC-UV for NICU allowing suppression of the formation of glycated insulin, to significantly reduce deviations from theoretical concentrations and to limit adsorption phenomena • This protocol is validated in case of co-infusion of parenteral nutrition.

Background Vancomycin is commonly used as part of empiric antibiotic therapy in the preterm infants who develop signs and symptoms of infection. Although skin necrosis has been noted to occur following injection of vancomycin into a peripheral vein in an adult patient, this complication has not been previously described in a preterm infant. Case presentation We report the case of a very low birthweight male infant born at 30 weeks gestational age who developed skin necrosis, most likely as a complication of vancomycin administration via a peripheral venous catheter. The immature skin and endothelial cells of this preterm infant may have increased the risk of drugs related venous and skin toxicity. In this case, assumption of a cumulative toxicity with other drugs administered concomitantly via the same catheter can’t be excluded. Conclusions To prevent the risk of skin damage, we advocate that in newborn infants, the administration of vancomycin should be limited to a concentration of

Skin necrosis caused by the administration of vancomycin via a peripheral venous catheter is rarely diagnosed. We report a case of a male infant born at 30 weeks’ gestational age who developed a skin necrosis, most probably related to vancomycin administration on a peripheral venous catheter. The frailty of this critically ill newborn probably increased its risk of exposition to adverse events. To prevent any damaging effect, the administration of vancomycin at a concentration lower than 2.5 mg/mL should be recommended when a central venous catheter is not available for the administration of injectable vancomycin in critically ill newborn.

The characterization of drug-drug interactions (DDIs) may require the use of several different tools, such as the thesaurus issued by our national health agency (i.e., ANSM), the metabolic pathways table from the Geneva University Hospital (GUH), and DDI-Predictor (DDI-P). We sought to (i) compare the three tools’ respective abilities to detect DDIs in routine clinical practice and (ii) measure the pharmacist intervention rate (PIR) and physician acceptance rate (PAR) associated with the use of DDI-P. The three tools’ respective DDI detection rates (in %) were measured. The PIRs and PARs were compared by using the area under the curve ratio given by DDI-P (RAUC) and applying a chi-squared test. The DDI detection rates differed significantly: 40.0%, 76.5%, and 85.2% for ANSM, GUH and DDI-P, respectively (p &lt, 0.0001). The PIR differed significantly according to the DDI-P’s RAUC: 90.0%, 44.2% and 75.0% for RAUC ≤ 0.5, RAUC 0.5–2 and RAUC &gt, 2, respectively (p &lt, 0.001). The overall PAR was 85.1% and did not appear to depend on the RAUC category (p = 0.729). Our results showed that more pharmacist interventions were issued when details of the strength of the DDI were available. The three tools can be used in a complementary manner, with a view to refining medication adjustments.

At admission, unintentional medication discrepancies (UMDs) can occur and may led to severe adverse events. Some of them are preventable through medication reconciliation (MR). As MR is a time-consuming activity, a better identification of high-risk patients of UMDs is mandatory. The objective was to identify risk factors associated with UMDs at admission in an internal medicine department. This prospective observational study was conducted from April 2017 to June 2019. At admission, inpatients had MR to obtain a complete list of home medications. This list was compared to prescriptions made at admission. All discrepancies were classified as intentional or UMDs. Univariate and multivariate analyses to identify the risk factors associated with UMDs were performed. MR was performed on 1157 patients (70.1 ± 16.8 years old); 550 MR (47.5%) contained at least one UMD. More than half of the UMDs (n = 892, 65.6%) corresponded to drug omission. The univariate analysis showed that age (> 60 years old), “living at home”, medication preparation not performed by patient, medication-intake difficulties, number of sources consulted, MR duration, presence of a high-risk drug and the number of home medications were associated with UMDs. In the multivariate analysis, adjusted on the number of sources consulted, independent risk factors were “living at home” and the number of home medications. At admission to an internal medicine department, UMDs were frequent and associated with “living at home” and poly-medication. Our findings might help physicians to identify high-risk patients of UMDs since their admission.

The preparation of chemotherapy drugs has always presented complex issues and challenges given the nature of the demand on the one hand, and the criticality of the treatments on the other. Chemotherapy involves handling special drugs that require specific precautions. These drugs are toxic and potentially harmful for people handling them. Their preparation entails therefore particular and complex procedures including preparation and control. The relevant control methods are often limited to the double visual control. The search for optimization and safety of pharmaco-technical processes leads to the use of new technologies with the main aim of improving patient care. In this respect, Augmented Reality (AR) technology can be an effective solution to support the control of chemotherapy preparations. It can be easily adapted to the chemotherapy drugs preparation environment. This paper introduces SmartPrep, an innovative decision support system (DSS) for the monitoring of chemotherapy drugs preparation. The proposed DSS uses the AR technology, through smart glasses, to facilitate and secure the preparation of these drugs. Controlling the preparation process is done with the help of the voice since hands are busy. SmartPrep was co-developed by the research laboratory CRISTAL, GRITA research group and the software publisher Computer Engineering.

Background Patients undergoing chemotherapeutic treatment are currently treated by a concomittent infusion of alizapride and ondansetron. To optimise the procedure and to ensure patients’ safety, the admixture could be prepared in advance by the Centralized Intravenous Additive Service (CIVAS) provided that the stability of the mixture has been proven beforhand to reduce nausea and vomiting. Aim of the study: to evaluate the long-term stability of an admixture of alizapride 0.926 mg/l and ondansetron 0.074 mg/ml in 0.9% sodium chloride polyolefin bags stored at 5 ± 3°C. Material and methods Five polyolefin bags containing 100 ml sodium chloride 0.9% added with 4 ml alizapride (100 mg) and 4 ml ondansetron (8 mg) were prepared in aseptic conditions and stored at 5 ± 3°C for 56 days. Periodically, physical stability tests were performed including: pH measurements, optical density measurements at 350, 410 and 550 nm to track turbidity appearance, visual and microscopical inspections to detect colour changes, precipitation, microaggregates or crystals. The concentrations of the solutions were measured by High Performance Liquid Chromatography coupled with an UV detector. Results There was no change in pH and optical densities during the study period. Visual and microscopical inspections didn’t show any change of colour neither precipitation, microaggregate or crystal. The alizapride and ondansetron concentrations remained stable over the study. Conclusion The admixture of alizapride and ondansetron in 0.9% sodium chloride solution polyolefin bags is physicochemically stable up to 56 days at 5 ± 3°C. These results support the possibility of preparing the solutions in advance by a CIVAS.

The use of long-term taurolidine locks (LTTL) seems to be effective in preventing catheter-related blood stream infections (CRBSI), especially in patients on home parenteral nutrition (HPN). This work targets the cost-effectiveness of LTTL in a cohort of adult HPN patients.A monocentric mirror-image design study was conducted in our referral centre among long-term HPN patients experiencing recurrent CRBSI. From 7th January 2011, LTTL were started after the third CRBSI episode within 12 months. CRBSI data was prospectively collected until 7th January 2013, in the same way as it had retrospectively been done before initiating LTTL. A cost-effective analysis was conducted to estimate the incremental costs and effects on CRBSI with LTTL. The efficacy of LTTL on CRBSI rate was assessed over 1000 days of catheter use.A total of 31,100 catheter days were analysed in 37 patients (median [interquartile range (IQR)]) aged 58 [42-68] years. The mean ± SD proven CRBSI rate was 3.18 ± 3.51 per 1000 catheter days before the introduction of LTTL and 0.39 ± 1.50 per 1000 catheter days after its introduction (p 0.0001). Considering both proven and probable CRBSI requiring hospital management, LTTL reduced by (mean [bootstrap CI 95%]) -2.63 [-3.26 to -2.06] infections per patient (from 2.89 [2.31 to 3.49] before to 0.26 [0.13 to 0.41] after) as well as incremental costs by -7 258 [-10 450 to -4 016] € (from 11 176 [8 004 to 14 968] € before to 3 918 [2 390 to 5 445] € after).Implementing LTTL to prevent recurrent CRBSI is cost-effective by dramatically decreasing their incidence.

Objectives: Home-Based Hospital (HBH) services concern patients of all ages suffering from conditions requiring technical care, close clinical monitoring, or hospital treatments that would normally...

Insulin aspart (Novorapid) is a rapid-acting insulin analog that is maintained in hexameric form by phenolic preservatives (phenol and metacresol) and stabilized by insulin-zinc complex. According to the manufacturers, insulin can be independently diluted either in 5% dextrose solution (D5%) or 0.9% sodium chloride solution. In reality, in most clinical units, such as the neonatal intensive care unit (NICU), insulin aspart is more frequently diluted in D5% than in saline solution due to sodium restriction. However, injectable dextrose solutions contain glucose degradation products (1) that are capable of binding proteins—like insulin—through a glycation phenomenon. Therefore, dilution of Novorapid in D5% would be more likely to cause glycated insulin and may raise a worrisome problem in terms of insulin stability. The objective of this study was to investigate the stability of insulin aspart diluted in D5% at both adult and neonate therapeutic concentrations in order to ensure its appropriateness in the preparation of insulin aspart. To address this issue, insulin aspart diluted in D5% was assayed by a stability-indicating method using high-performance liquid chromatography (HPLC) coupled with an ultraviolet (UV) detector. The nature of the formed product was determined by HPLC coupled with a mass spectrometer. The effect of …

Background : In previous studies, the choice of doses of tranexamic acid was empirically defined as no pharmacokinetic study had been conducted in haemorrhagic caesarean section. Objective : The objective was to build a pharmacokinetic model in patients receiving a single 0.5, 1 or 2 g intravenous bolus. Method : A preliminary monocentric open study was performed in the Lille centre. Blood samples and one urinary sample were collected in the 6 hours following the injection. Nine patients were included. Tranexamic acid concentration was measured using liquid chromatography system coupled with tandem mass spectrometry. We used Monolix 2019R1 for population pharmacokinetic modelling. A structural model was constructed followed by the investigation of potential covariates. Results : Data were best described with a two-compartment model with a double first-order elimination from the central compartment. The model was improved when the variable ideal weight per dose was affected as a covariate for the apparent volume of distribution. Assuming a dose of 1 g and a height of 160 cm, the pharmacokinetic parameters were estimated at 10.26 L.h−1 for total clearance, 11.5 L for the volume of the central compartment, 15.8 L for the volume of the second compartment, a diffusional clearance of 30.36 L.h−1 , and a urinary excretion fraction of 25.8%. Conclusions : The population pharmacokinetic model of tranexamic acid in haemorrhagic caesarean section was successfully established in our tiny sample of patients. The results of this preliminary TRACES pharmacokinetic study suggested that elimination of tranexamic acid is partially non urinary in contrast with healthy patients.

Resume Introduction Le patient greffe renal est expose a un risque accru de iatrogenie medicamenteuse (IM). Le but de l’etude est de mesurer l’impact des interventions du pharmacien clinicien sur l’IM evitable. Materiel et methode Les cas d’IM ont ete recueillis sur 3 periodes : sans intervention, avec conciliation medicamenteuse (CM) d’entree, et avec une CM d’entree et entretien pharmaceutique de sortie. Les cas d’IM ont ete classes selon leur nature, leur gravite et leur evitabilite. Resultats Les patients inclus etaient majoritairement des hommes, d’environ 55 ans, en stade 3 d’IRC, greffes depuis moins de 3 mois ou depuis plus d’un an, avec des facteurs de risque cardiovasculaire, une nephropathie polykystique et en moyenne 9 medicaments/jour. Vingt pour cent des cas d’IM etaient evitables et majoritairement graves. A la periode 1, 27,7 % des patients presentaient au moins un cas d’IM, 21,3 % a la periode 2, et 17,4 % a la periode 3 (p = 0,03). Cent dix patients ont eu une CM a l’entree avec en moyenne 0,6 divergence non intentionnelle/patient. Elle portait surtout sur des oublis de medicament (81 %) et concernait des medicaments des voies digestives et metaboliques (24,5 %), du systeme cardiovasculaire (23 %) et du systeme nerveux (23 %). Soixante-huit entretiens pharmaceutiques de sortie ont ete realises, revelant des pratiques d’automedication. Conclusion Notre etude montre qu’une CM d’entree associee a un entretien pharmaceutique de sortie pourrait etre benefique pour reduire l’IM chez le patient greffe renal. Il serait licite d’envisager une etude specifique pour conforter ces resultats.

Resume Objectifs Il est reconnu que la manipulation de medicaments conditionnes en ampoules de verre peut generer des particules lors de l’ouverture de l’ampoule. L’utilisation d’aiguilles filtrantes lors du prelevement de medicaments conditionnes en ampoules de verre est recommandee par plusieurs auteurs pour diminuer la contamination particuliere. L’objectif principal est d’etablir un etat des lieux entourant l’utilisation des aiguilles filtrantes et la perception des pharmaciens au Quebec et en France. Methodes Il s’agit d’une etude descriptive transversale. Un questionnaire a ete envoye a tous les etablissements de sante au Quebec (n = 30) et une selection d’hopitaux en France (n = 100). Les repondants etaient invites a repondre a un questionnaire incluant la presence de politiques et procedures sur l’utilisation des aiguilles filtrantes ainsi que le recours a ces dispositifs et leurs modalites d’utilisation a la pharmacie et dans les services. Resultats Au total, 27 repondants quebecois (taux de reponse : 90 %) et 41 repondants francais (taux de reponse : 41 %) ont participe a notre enquete. Au Quebec, tous les questionnaires exploitables sauf un (42/43) rapportent un recours aux aiguilles filtrantes de cinq microns a la pharmacie contre 28 % des repondants dans les unites de soins. En France, cette pratique est quasiment ignoree. Conclusions Des actions doivent etre envisagees pour statuer sur l’utilisation des aiguilles filtrantes notamment des etudes pour confirmer les consequences de la presence de ces particules sur un modele animal, des discussions avec les autorites reglementaires afin de clarifier la situation, encourager les fabricants a utiliser le conditionnement en flacons.

International audience; Background: Phlebitis is a common side effect of vancomycin peripheral intravenous (PIV) infusion. As only one PIV catheter is frequently used to deliver several drugs to hospitalized patients through the same Y-site, perturbation of the infusion flow by hydration or other IV medication may influence vancomycin exposure to endothelial cells and modulate toxicity. Methods: We assessed the toxicity of variations in vancomycin concentration induced by drug mass flow variations in human umbilical vein endothelial cells (HUVECs), simulating a 24 h multi-infusion therapy on the same line. Results were expressed as the percentage of viable cells compared with a 100% control, and the Kruskal–Wallis test was used to assess the toxicity of vancomycin. Results: Our results showed that variations in vancomycin concentration did not significantly influence local toxicity compared to a fixed concentration of vancomycin. Nevertheless, the loss of cell viability induced by mechanical trauma mimicking multidrug infusion could increase the risk of phlebitis. Conclusion: To ensure that vancomycin-induced phlebitis must have other causes than variation in drug mass flow, further in vitro experiments should be performed to limit mechanical stress to frequent culture medium change.

Resume Introduction L’evolution de la place du patient dans sa prise en charge implique qu’il ait acces a une information claire, complete et comprehensible. Le niveau de connaissance des patients et la qualite du transfert de l’information fournie par le chirurgien ne sont pas connus avec precision aussi nous avons mene une etude prospective observationnelle afin d’evaluer : (1) le niveau de connaissance des patients au cours de leur prise en charge, (2) la qualite du transfert d’information, (3) le besoin en information, (4) les facteurs influencant le niveau de connaissance. Hypothese Le niveau de connaissance des patients evolue au cours de leur parcours medical. Patients et methodes Nous avons mene une etude monocentrique prospective, entre janvier 2014 et mars 2015 en consultation et durant l’hospitalisation de 63 patients ayant beneficie d’une arthroplastie de hanche (n = 36) ou de genou (n = 27). Un meme observateur assistait a toutes les consultations et consignait les donnees transmises par le chirurgien. Les patients completaient un auto-questionnaire a l’issue de la consultation (T1), a leur entree dans le service (T2) et a leur sortie apres l’arthroplastie (T3). Le niveau de connaissance et le besoin d’information des patients etaient apprecies a l’aide de scores semi-quantitatifs et le transfert d’information en analysant la concordance entre les informations donnees par le chirurgien et les reponses des patients. Resultats Le score moyen de connaissance global etait de 17,22 ± 6,33 sur 42 a T1 et progressait au cours de la prise en charge : score superieur a T3 (19,44 ± 6,89) vs T1. La connaissance des complications etait superieure a T1 vs T3 (2,67 ± 1,98 vs 2,19 ± 1,91 ; p Discussion L’originalite de notre etude etait d’apprecier l’evolution des connaissances des patients au cours de leur prise en charge revelant un niveau de connaissance relativement bas et tres variable selon le sujet et le moment de la prise en charge. Cette etude montre la necessite d’informer le patient tout au long de sa prise en charge sans negliger la sortie, moment ou la demande d’information etait la plus forte. Niveau de preuve Niveau IV, etude prospective observationnelle sans groupe temoin.

Introduction Depuis 4 ans, les premiers biosimilaires (BS) de l’etanercept (ETA) et l’adalimumab (ADA) sont commercialises : 2 pour ETA (BE1 et BE2) et 5 pour ADA (BA1 a BA5). Leurs avantages reposent sur un cout moindre avec une efficacite, securite et tolerance similaires au princeps (PS). Apres acceptation de nos projets d’accompagnement du recours aux BS dans le cadre d’appels a projets DGOS (article 51), nous avons suivi les patients interchanges du PS au BS. L’objectif est de faire un etat des lieux du maintien du BS apres l’interchangeabilite (IC). Materiels et methodes Etude monocentrique, prospective, observationnelle evaluant en vie reelle l’efficacite, la tolerance et la satisfaction des patients souffrant d’un rhumatisme inflammatoire chronique (RIC) traites par un BS et ayant prealablement ete traites par le PS. La periode d’observation s’est etendue d’aout 2019 a aout 2020 pour des patients interchanges entre le 1er janvier 2019 et le 31 decembre 2019. Apres au moins 2 mois d’IC, un pharmacien hospitalier (PhH) rappelait les patients pour recueillir leur ressenti. Resultats En 2019, la file active des patients traites par ADA et ETA et beneficiant d’une consultation pour un RIC est de 351 patients (49,9 % sous ADA et 50,1 % sous ETA) d’âge moyen 53 ans [15 ; 91] et dont l’anciennete moyenne du RIC etait de 13,5 ans [0 ; 49]. Les consultations ont donne lieu a 39 % d’IC vers un BS (57 ADA et 80 ETA), 31,1 % de poursuite du PS (65 ADA et 44 ETA), 23,1 % d’initiations de BS (37 ADA et 44 ETA), 6 % d’initiations de PS (16 ADA et 5 ETA) et 0,8 % de poursuite du BS (3 ETA). Sur 246 patients sous PS, l’IC a ete proposee a 183 patients (74 %) dont 137 acceptations (57 ADA et 80 ETA). Les motifs de non proposition etaient principalement : 33,9 % de patients ayant un RIC difficile a equilibrer, 27,4 % de patients pressentis comme refractaire et 25,8 % par manque de temps. Les rapports d’IC entre BS etaient pour l’ETA : 47,5 % de BE1 et 52,5 % de BE2 ; et pour l’ADA : 35,1 % de BA1, 22,8 % de BA2, 7 % de BA3, 5,3 % de BA4 et 29,8 % de BA5. Le PhH a rappele les patients en moyenne 7 mois [2 ; 15] apres l’instauration du BS. Au total, 118 patients (86,1 %) ont repondu (51 sous ADA et 67 sous ETA). Le taux de maintien du BS est de 77,1 % (n = 91) (70 % sous BS d’ADA et 82 % sous BS d’ETA). Les motifs d’arret evoques par les patients sont divers voire multiples. Pour BE1 (13,3 % d’arrets) : 75 % pour perte d’efficacite ressentie (PER), 25 % pour douleur a l’injection (DI) et 25 % pour dispositif insatisfaisant. Pour BE2 (18,9 % d’arrets) : 71,5 % pour PER, 85,7 % pour DI. Pour BA1 (3/18 arrets) : 100 % pour PER 33,3 % pour DI et 66,6 % pour survenue d’effets indesirables (EI). Pour BA2 (2/12 arrets) : 100 % pour PER. Pour BA3 (2/4 arrets) : 50 % pour PER et 50 % pour EI. Pour BA4 (1/2 arrets) : 100 % pour EI. Pour BA5 (6/15 arrets) : 66,6 % pour PER, 83 % pour DI et 33,3 % pour EI. Discussion Dans la litterature, peu d’etudes en vie reelle ont ete publiees sur l’IC d’ADA et ETA. On retrouve une etude* sur BA5 en Italie (n = 82 patients), seuls 2 % des patients ont arrete le BS pour EI et PER. Une augmentation de la douleur a 3 mois a ete montree (NS) revenant a la valeur de base a 6 mois, 33 % ont eu un EI a 3 mois, ce qui concorde avec notre resultat. Conclusion Cette methodologie a permis de recueillir directement le ressenti des patients. Pres de 85 % de nos patients interchanges sont toujours stabilises avec le BS. En comptant l’aspect subjectif du ressenti des patients, c’est un resultat encourageant dans le cadre de la promotion et du deploiement des BS dans les RIC.

Potentially toxic plasticizers are commonly added to polyvinyl chloride medical devices for transfusion in order to improve their flexibility and workability. As the plasticizers are not chemically bonded to the PVC, they can be released into labile blood products (LBPs) during storage. Ideally, LBPs would be used in laboratory studies of plasticizer migration from the medical device. However, short supply (i.e., limited stocks of human blood in collection centres) has prompted the development of specific simulants for each type of LBP in the evaluation of new transfusion devices. We performed a Delphi study with a multidisciplinary panel of 24 experts. In the first (qualitative) phase, the panel developed consensus definitions of the specification criteria to be met by each migration simulant. Next, we reviewed the literature on techniques for simulating the migration of plasticizers into LBPs. A questionnaire was elaborated and sent out to the experts, and the replies were synthesized in order to obtain a consensus. The qualitative study established specifications for each biological matrix (whole blood, red blood cell concentrate, plasma, and platelet concentrate) and defined the criteria required for a suitable LBP simulant. Ten criteria were suggested: physical and chemical characteristics, opacity, form, stability, composition, ability to mimic a particular clinical situation, ease and safety of use, a simulant–plastic interaction correlated with blood, and compatibility with analytical methods. The questionnaire data revealed a consensus on the use of natural products (such as pig’s blood) to mimic the four LBPs. Opinions diverged with regard to synthetic products. However, an isotonic solution and a rheological property modifier were considered to be of value in the design of synthetic simulants. Consensus reached by the Delphi group could be used as a database for the development of simulants used to assess the migration of plasticizers from PVC bags into LBPs.