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The compounding of injectable cancer drugs for clinical trials often requires specific procedures, with limited access to the starting materials and especially the active compound. These characteristics prevent the application of qualitative or quantitative analyses and quality control techniques. Hence, for some very complex compounding operations, double visual inspection is considered to be less reliable, more time-consuming and more human-resource-intensive than other methods. The compounding team at Lille University Hospital (Lille, France) has equipped one of its preparation areas with a new device: augmented reality (AR) eyewear connected to an oncology drug management system, as a support tool for compounding and quality control. The tool has been tested, adapted and improved within the unit and is now used for investigational drug compounding on a routine basis. In a prospective, single-centre study, we evaluated the feasibility of the implementation of this novel AR approach for the compounding of injectable investigational cancer drugs. During the 6-month study period, 564 clinical trial compounding operations were performed with the AR eyewear. The proportion of poor-quality photos taken with the AR eyewear fell over time, as users became more familiar with the tool. A user satisfaction survey highlighted a very high level of uptake and a wish to broaden the scope of the compounding performed with AR support. The AR eyewear constitutes an innovative, cost-effective tool that increased the level of safety without disrupting the unit's operating procedures. The tool's flexibility enabled its integration into a variety of working environments. The various improvements now being developed should help to further boost the added value of this novel device.

Background: Psychosocial interventions for caregivers of patients with Alzheimer disease and relative dementias (ADRD) reported a caregiver burden improvement. Multicomponent intervention integrating pharmaceutical care has not yet been evaluated while ADRD patients and their caregivers are exposed to high risk of drug-related problems. The PHARMAID study aimed to assess the impact of personalized pharmaceutical care integrated to a psychosocial program on the burden of ADRD caregivers at 18 months. Methods: The PHARMAID RCT was conducted between September 2016 and June 2020 [ClinicalTrials.gov: NCT02802371]. PHARMAID study planned to enroll 240 dyads, i.e. ADRD patients and caregivers, whose inclusion criteria were: outpatient with mild or major neurocognitive disorders due to ADRD, living at home, receiving support from a family caregiver. Three parallel groups compared a control group with two interventional groups: psychosocial intervention and integrated pharmaceutical care at a psychosocial intervention. The main outcome was the caregiver burden assessed by the Zarit Burden Index (ZBI, score range 0–88) at 18 months. Results: Overall, 77 dyads were included (32% of the expected sample size). At 18 months, the mean ZBI scores were 36.7 ± 16.8 in the control group, 30.3 ± 16.3 for the group with psychosocial intervention, and 28.8 ± 14.1 in group with integrated pharmaceutical care at psychosocial intervention. No significant difference was demonstrated between the three groups (p = 0.326). Conclusions: The findings suggest that PHARMAID program had no significant impact on caregiver burden at 18 months. Several limitations have been highlighted and discussed by the authors in order to formulate recommendations for further research.

IntroductionPotentially inappropriate prescriptions (PIPs) of antidiabetic drugs (ADs) (PIPADs) to patients with type 2 diabetes mellitus (T2DM) have been reported in some studies. The detection of PIPs in electronic databases requires the development of explicit definitions. This approach is widely used in geriatrics but has not been extended to PIPADs in diabetes mellitus. The objective of the present literature review was to identify all explicit definitions of PIPADs in patients with T2DM.Materials and methodsWe performed a systematic review of the literature listed on Medline (via PubMed), Scopus, Web of Science, and, Embase between 2010 and 2021. The query included a combination of three concepts ("T2DM" AND "PIPs" AND "ADs") and featured a total of 86 keywords. Two independent reviewers selected publications, extracted explicit definitions of PIPADs, and then classified the definitions by therapeutic class and organ class.ResultsOf the 4,093 screened publications, 39 were included. In all, 171 mentions of PIPADs (corresponding to 56 unique explicit definitions) were identified. More than 50% of the definitions were related to either metformin (34%) or sulfonylureas (29%). More than 75% of the definitions were related to either abnormal renal function (56%) or age (22%). In addition, 20% (n = 35) mentions stated that biguanides were inappropriate in patients with renal dysfunction and 17.5% (n = 30) stated that sulfonylureas were inappropriate above a certain age. The definitions of PIPADs were heterogeneous and had various degrees of precision.ConclusionOur results showed that researchers focused primarily on the at-risk situations related to biguanide prescriptions in patients with renal dysfunction and the prescription of sulfonylureas to older people. Our systematic review of the literature revealed a lack of consensus on explicit definitions of PIPADs, which were heterogeneous and limited (in most cases) to a small number of drugs and clinical situations.

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BackgroundResidual contamination by intravenous conventional antineoplastic drugs (ICAD) is still a daily issue in hospital facilities. This study aimed to compare the efficiency (EffQ) of 4 different solutions to remove 23 widely used ICADs from surfaces.Method and findingsA solution containing 23 ICADs (4 alkylating agents, 8 antimetabolites, 2 topo-I inhibitors, 6 topo-II inhibitors and 3 spindle poisons) was spread over 100 cm2 stainless steel. After drying, decontamination was carried out using 10×10 cm wipes moistened with 300 μL of one of the following solutions: 70% isopropanol (S1); ethanol-hydrogen peroxide 91.6-50.0 mg/g (S2); 10-2 M sodium dodecyl sulphate/isopropanol 80/20 (S3) or 0.5% sodium hypochlorite (S4). Six tests were performed for each decontamination solution. Two modalities were tested: a single wipe motion from top to bottom or vigorous wiping (n = 6 for each modality). Residual contamination was measured with a validated liquid chromatography with tandem mass spectrometry detection method. Solution efficiency (in %) was computed as follows: EffQ = 1-(quantity after decontamination/quantity before decontamination), as median (min-max) for the 23 ICADs. The overall decontamination efficiency (EffQ) of the 4 solutions was compared by a Kruskall-Wallis test. Decontamination modalities were compared for each solution and per ICAD with a Mann-Whitney test (pConclusionDecontamination efficiency depended on the solution used but also on the application modality. An SDS admixture seems to be a good alternative to sodium hypochlorite, notably after vigorous chemical decontamination with no hazard either to materials or workers.

Care management of newborns in the neonatal intensive care unit (NICU) requires numerous PVC (PolyVinyl Chloride) medical devices (MD) containing plasticizers that can migrate and contaminate the patient. We measured the magnitude of neonates’ exposure to plasticizers (di-ethylhexylphthalate (DEHP) and alternatives) in relation to urinary concentrations of their metabolites. Plasticizers’ exposure was evaluated (1) by calculating the amounts of plasticizers prone to be released from each MD used for care management, and (2) by measuring the patients’ urinary levels of each plasticizers’ metabolites. 104 neonates were enrolled. They were exposed to di-isononylphthalate (DINP), especially via transfusion and infusion MD, and to DEHP via ECMO (Extra Corporeal Membrane Oxygenation) and respiratory assistance MD. Mean exposure doses exceeded the derived no-effect level of DINP and DEHP by a 10-fold and a 1000-fold factor. No PVC MD were plasticized with di-isononylcyclohexane-1,2-dicarboxylate (DINCH). High urinary concentrations of DEHP metabolites were directly correlated with DEHP exposure through ECMO MD. Urinary concentrations of DINP metabolites in transfused patients were also high. DINCH metabolites were found in urine, suggesting another route of exposure. Neonates in NICU are considerably exposed to plasticizers, with magnitudes varying with the type of MD used. The high exposure to DEHP and DINP leads to a risk of their metabolites’ toxicity.

Introduction: Drug incompatibilities are among the most common medication errors in intensive care units. A precipitate can form and block the catheter or cause an adverse event in the patient. Intensive care units have implemented various strategies for limiting the occurrence of these incompatibilities, which have already been studied in vitro under standardized conditions. The objective of the present in vitro study was to continue these assessments by determining the impact of the infusion line geometry and the drugs’ position in the infusion set-up on the prevention of vancomycin–piperacillin/tazobactam incompatibility. Methods: Infusion lines with a different common volume, a multilumen medical infusion device, a dilute vancomycin solution, and separate infusions of incompatible drugs were evaluated separately. The infusion line outlet was connected to a dynamic particle counter. Results: Reducing the common volume, using multilumen medical devices, or spacing out the two incompatible drugs on the infusion line did not prevent the occurrence of a significant particulate load. Only dilution of the vancomycin solution was associated with a significantly lower particulate load and the absence of drug incompatibility. Conclusions: Our results show that under specific conditions, it is possible to reduce particulate contamination considerably.

Bacterial respiratory tract infections (e.g., in patients with cystic fibrosis) may be treated with the intravenous infusion of a piperacillin/tazobactam (P/T) solution through an elastomeric device. In the present work, we combined a 24-h drug stability study with an assessment of the drug solution flow rate during an in vitro simulated infusion. Experiments were performed in triplicate with two excipient-free generic P/T solutions and an excipient-containing proprietary P/T solution in saline (all 50/6.25 mg/mL) released from an elastomeric infusion device at 32 °C. The P/T solutions’ stability was assessed by an HPLC-UV assay, pH and osmolality measurements, a visual assessment, and particle counting. Before these analyses, a forced degradation study was performed. To assess the flow rate, a precision scale was used to weigh the solution collected at the infusion line outlet. The stability criteria were

To avoid the failures in therapy with psychotropic drugs, treatments can be personalized by applying the results of therapeutic drug monitoring and pharmacogenetic testing. The objective of the present single-center observational study was to describe the changes in psychotropic drug management prompted by therapeutic drug monitoring and pharmacogenetic testing, and to compare the effective drug concentration based on metabolic status with the dose predicted using an in silico decision tool for drug–drug interactions. The study was conducted in psychiatry wards at Lille University Hospital (Lille, France) between 2016 and 2020. Patients with data for at least one therapeutic drug monitoring session or pharmacogenetic test were included. Blood tests were performed for 490 inpatients (mainly indicated by treatment monitoring or failure) and mainly concerned clozapine (21.4%) and quetiapine (13.7%). Of the 617 initial therapeutic drug monitoring tests, 245 (40%) complied with good sampling practice. Of the patients, 51% had a drug concentration within the therapeutic range. Regardless of the drug concentration, the drug management did not change in 83% of cases. Thirty patients underwent pharmacogenetic testing (twenty-seven had also undergone therapeutic drug monitoring) for treatment failure; the plasma drug concentration was outside the reference range in 93% of cases. The patient’s metabolic status explained the treatment failure in 12 cases (40%), and prompted a switch to a drug metabolized by another CYP450 pathway in 5 cases (42%). Of the six tests that could be analyzed with the in silico decision tool, all of the drug concentrations after adjustment were included in the range estimated by the tool. Knowledge of a patient’s drug concentration and metabolic status (for CYD2D6 and CYP2C19) can help clinicians to optimize psychotropic drug adjustment. Drug management can be optimized with good sampling practice, support from a multidisciplinary team (a physician, a geneticist, and clinical pharmacist), and decision support tools.

Abstract 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

Background: Drug incompatibility is defined as a physical-chemical reaction between two or more injectable drugs and that results mainly in precipitation or insolubility. Several strategies for reducing incompatibilities have been implemented empirically in intensive care units. However, these strategies have never been compared directly (and particularly in terms of the particulate load and drug mass flow rate) under standardized conditions. The objective of the present in vitro study was to evaluate the impact of various strategies for preventing incompatibility between simultaneously infused vancomycin and piperacillin/tazobactam. Methods: An in-line filter, a dilute vancomycin solution (5 mg/mL), and an alternative saline administration line were evaluated separately. The infusion line outlet was connected to a dynamic particle counter. The antibiotic concentration was measured in an HPLC-UV assay. Result: The use of an in-line filter and an alternative saline administration route did not significantly reduce the particulate load caused by vancomycin-piperacillin/tazobactam incompatibility. Dilution of the vancomycin solution was associated with a significantly lower particulate load and maintenance of the vancomycin mass flow rate. Discussion: It is important to systematically compare the efficacy of strategies for preventing drug incompatibility. The use of diluted vancomycin solution gave the best results in the case of vancomycin-piperacillin/tazobactam incompatibility.

Abstract Background The community pharmacist is a key player in medication reviews of older outpatients. However, it is not always clear which individuals require a medication review. The objective of the present study was to identify high-priority older patients for intervention by a community pharmacist. Methods As part of their final-year placement in a community pharmacy, pharmacy students conducted 10 interviews each with older adults (aged 65 or over) taking at least five medications daily. The student interviewer also offered to examine the patient’s home medicine cabinet. An interview guide was developed by an expert group to assess the difficulties in managing and taking medications encountered by older patients. Results The 141 students interviewed a total of 1370 patients (mean age: 81.5; mean number of medications taken daily: 9.3). Of the 1370 interviews, 743 (54.2%) were performed in the patient’s home, and thus also included an examination of the home medicine cabinet. Adverse events were reported by 566 (42.0%) patients. A total of 378 patients (27.6%) reported difficulties in preparing, administering and/or swallowing medications. The inspections of medicine cabinets identified a variety of shortcomings: poorly located cabinets (in 15.0% of inspections), medication storage problems (21.7%), expired medications (40.7%), potentially inappropriate medications (15.0%), several different generic versions of the same drug (19.9%), and redundant medications (20.4%). Conclusions In a community pharmacy setting, high-priority older patients for intervention by a community pharmacist can be identified by asking simple questions about difficulties in managing, administering, taking or storing medications.

Abstract Background Catheter-related bacteremia (CRB) is the most frequent nosocomial infection in neonatal intensive care unit (NICU) patients, especially in very low-birth-weight infants. Administration of injectable drugs in premature newborn infants has many particularities and several types of infusion incidents have been reported. The Edelvaiss® Multiline NEO device is a novel multi-lumen access infusion device adapted to the specificities of infusion in neonatology. This multicenter, randomized, controlled study was therefore designed to determine whether or not Edelvaiss® Multiline NEO reduces the risk of CRB in preterm newborn infants in an NICU. Methods/design This is a multicenter, randomized, controlled trial, using a cluster-randomized crossover design. Four investigator centers (four clusters) will participate in the study and will be randomized into two groups, corresponding to two different sequences (either the Edelvaiss® Multiline NEO or standard infusion system sequence, then vice versa). A total of 280 patients will be recruited. Infants will be enrolled in the study at the time of placing a single-lumen central venous catheter. Three visits recording specific data are planned in the study protocol. The primary outcome measure is the incidence density (ID) of CRB. For each patient, the total number of catheters and CRB incidents as well as the duration of stay in the NICU will be computed and considered for analysis. Discussion The study will provide high-quality evidence to determine whether the Multiline NEO device reduces the risk of CRB in preterm newborns in NICUs or not. Trial registration ClinicalTrials.gov, NCT02633124. Registered on 7 December 2015.

Abstract Background In critically ill patients, drug incompatibilities frequently occur because of the number of drugs to be administered through a limited number of infusion lines. These are among the main causes of particulate contamination. However, little data is available to quantify particle exposure during simultaneous IV-drug infusion. The objective of this study was to evaluate the particulate matter potentially administered to critically ill patients. Methods The particulate matter (between 1 μm and 30 mm) of infused therapies used in ICUs for patients suffering from either septic shock or acute respiratory distress syndrome was measured in vitro over 6 h using a dynamic image analysis device, so that both overall particulate contamination and particle sizes could be determined. Data is presented according to the recommendations of the European Pharmacopoeia (≥ 10 and 25 μm). Results For the six experimental procedures (continuous infusion of norepinephrine, midazolam, sufentanil, heparin, 5% glucose, binary parenteral nutrition and discontinuous administrations of omeprazole, piperacillin/tazobactam and fluconazole), the overall number of particles over the 6-h infusion period was 8256 [5013; 15,044]. The collected values for the number of particles ≥ 10 and 25 μm were 281 [118; 526] and 19 [7; 96] respectively. Our results showed that discontinuous administrations of drugs led to disturbances in particulate contamination. Conclusions This work indicates the amount of particulate matter potentially administered to critically ill adult patients. Particulate contamination appears lower than previous measurements performed during multidrug IV therapies in children.

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.

Background Glucose control is an important issue in post-operative patients. The objective here was to compare two insulin infusion lines by syringe pumps to assess the impact of medical devices on glycaemic variability in surgical patients under intensive insulin therapy. This open, prospective, single-centre randomised study was conducted in a fifteen-bed perioperative high dependency unit (HDU) in a university hospital. In total, 172 eligible patients receiving insulin therapy agreed to participate in the study. Subcutaneous continuous glucose monitoring was set up for all patients and an optimised system with a dedicated insulin infusion line for half of the patients. Results Eighty-six patients were infused via the optimised infusion line and 86 patients via the standard infusion line. No significant difference was found according to the glycaemic lability index score [mean difference between groups (95% CI): −0.09 (−0.34; 0.16), p = 0.49 after multiple imputation]. A glucose control monitoring system indicated a trend towards differences in the duration of hypoglycaemia (blood glucose level below 70 mg dl−1 (3.9 mmol l−1) over 1000 h of insulin infusion (9.7 ± 25.0 h in the standard group versus 4.4 ± 14.8 h in the optimised group, p = 0.059) and in the number of patients experiencing at least one hypoglycaemia incident (25.7 vs. 12.9%, p = 0.052). Time in the target range was similar for both groups. Conclusions The use of optimised infusion line with a dedicated insulin infusion line did not reduce glycaemic variability but minimised the incidence of hypoglycaemia events. The choice of the medical devices used to infuse insulin seems important for improving the safety of insulin infusion in perioperative HDU.

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.

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 (The National Agency for the Safety of Medicines and Health Products), GUH and DDI-P, respectively (p < 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 > 2, respectively (p < 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.

Background: In neonatal intensive care units (NICUs), the simultaneous administration of drugs requires complex infusion methods. Such practices can increase the risk of drug incompatibilities resulting in the formation of a particulate load with possible clinical consequences. Methods: This paper evaluates strategies to reduce the particulate load of a protocol commonly used in NICUs with a potential medical incompatibility (vancomycin/cefepime combination). The protocol was reproduced in the laboratory and the infusion line directly connected to a dynamic particle counter to evaluate the particulate matter administered during infusion. A spectrophotometry UV assay of cefepime evaluated the impact of filters on the concentration of cefepime administered. Results: A significant difference was observed between the two infusion line configurations used in the NICU, with higher particulate load for cefepime infused via the emergency route. There was no change in particulate load in the absence of vancomycin. A filter on the emergency route significantly reduced this load without decreasing the cefepime concentration infused. Preparation of cefepime seemed to be a critical issue in the protocol as the solution initially contained a high level of particles. Conclusion: This study demonstrated the impact of a reconstitution method, drug dilution and choice of infusion line configuration on particulate load.

BACKGROUND:Despite the use of closed system drug transfer devices (CSTD), residual contamination from antineoplastic drugs is still detected inside isolators. The aim of this study was to compare the decontamination level obtained using a CSTD + standard cleaning procedure with a CSTD + standard cleaning procedure + specific decontamination procedure. METHODS AND FINDINGS:A comparative and prospective study was carried out in a newly opened compounding unit. Compounding was performed with a CSTD (BD-Phaseal, Becton-Dickinson). In the Control isolator (C), the cleaning process was completed daily with a standard biocide solution (AnioxysprayTM, Anios, France). In the Intervention isolator (I), weekly decontamination with a homemade admixture of sodium dodecyl sulfate 10(-2) M/70% isopropanol (80/20, v/v) was added. Monitoring was performed via a validated LC-MS/MS method. Eight drugs (cyclophosphamide, cytarabine, dacarbazine, fluorouracile, gemcitabine, ifosfamide, irinotecan and methotrexate) were monitored daily over 14 consecutive weeks on three sites inside the isolators: gloves, workbench and window. Results are presented as the odds-ratio (OR) of contamination and as overall decontamination efficiency (EffQ, %). The proportion of EffQ ≥ 90% was assessed by a Fisher's exact test (p

Insulin is a frequently prescribed drug in hospitals and is usually administered by syringe pumps with an extension line which can be made of various materials. Two insulin solutions were studied: an insulin analogue, Novorapid® which contains insulin aspart and two phenolic preservatives (e.g. phenol and metacresol) and Umuline rapide® with human insulin and metacresol as preservative. Some studies have indicated interactions between insulin, polyvinyl chloride (PVC) and polyethylene (PE). The aim of this work was to study such interactions between Novorapid® or Umuline rapide® and infusion extension line materials (PVC, PE and coextruded (PE/PVC)). Insulin solution at 1 IU/mL was infused at 2 mL/h over 24 hours with 16 different extension lines (8 in PVC, 3 in PE and 5 in PE/PVC). Ultra-Fast Liquid Chromatography with diode array detection (UFLC-DAD) was performed to quantify insulin (human and aspart) and preservatives (metacresol and phenol). Limited human insulin sorption was observed thirty minutes after the onset of infusion: 24.3 ± 12.9%, 3.1 ± 1.6% and 18.6 ± 10.0% for PVC, PE and PE/PVC respectively. With insulin aspart, sorption of about 5% was observed at the onset of infusion for all materials. However, there were interactions between phenol and especially metacresol with PVC, but no interactions with PE and PE/PVC. This study shows that insulin interacts with PVC, PE and PE/PVC at the onset of infusion. It also demonstrates that insulin preservatives interact with PVC, which may result in problems of insulin conservation and conformation. Some more studies are required to understand the clinical impact of the latter during infusion.

The objective of this randomized, prospective and controlled study was to investigate the ability of a closed-system transfer device (CSTD; BD-Phaseal) to reduce the occupational exposure of two isolators to 10 cytotoxic drugs and compare to standard compounding devices.The 6-month study started with the opening of a new compounding unit. Two isolators were set up with 2 workstations each, one to compound with standard devices (needles and spikes) and the other using the Phaseal system. Drugs were alternatively compounded in each isolator. Sampling involved wiping three surfaces (gloves, window, worktop), before and after a cleaning process. Exposure to ten antineoplastic drugs (cyclophosphamide, ifosfamide, dacarbazine, 5-FU, methotrexate, gemcitabine, cytarabine, irinotecan, doxorubicine and ganciclovir) was assessed on wipes by LC-MS/MS analysis. Contamination rates were compared using a Chi2 test and drug amounts by a Mann-Whitney test. Significance was defined for p

PURPOSE:Plastic materials such as polyurethane (PUR), polyethylene (PE), polypropylene (PP) and polyvinyl chloride (PVC) are widely used in double-lumen extension tubing. The purposes of our study were to 1) compare in vitro drug delivery through the double extension tubes available on the market 2) assess the plastic properties of PUR in infusion devices and their impact on drug delivery. METHODS:The study compared eight double-lumen extension tubes in PUR, co-extruded (PE/PVC) plastic and plasticised PVC from different manufacturers. Isosorbide dinitrate and diazepam were used as model compounds to evaluate their sorption on the internal surface of the infusion device. Control experiments were performed using norepinephrine known not to absorb to plastics. Drug concentrations delivered at the egress of extension tubes were determined over time by an analytical spectrophotometric UV-Vis method. The main characteristics of plastics were also determined. RESULTS:Significant differences in the sorption phenomenon were observed among the eight double-lumen extension tubes and between pairs of extension tubes. Mean concentrations of isosorbide dinitrate delivered at the egress of double-lumen extension tubes after a 150-minute infusion (mean values ± standard deviation in percentage of the initial concentrations in the prepared syringes) ranged between 80.53 ± 1.66 (one of the PUR tubes) and 92.84 ± 2.73 (PE/PVC tube). The same parameters measured during diazepam infusion ranged between 48.58 ± 2.88 (one of the PUR tubes) and 85.06 ± 3.94 (PE/PVC tube). The double-lumen extension tubes in PUR were either thermosetting (resin) or thermoplastic according to reference. CONCLUSIONS:Clinicians must be aware of potential drug interactions with extension tube materials and so must consider their nature as well as the sterilisation method used before selecting an infusion device.