A proof of principle study using radiopharmaceuticals to quantify and localize container-content interactions in medical syringes.

The sorption of drugs onto their contents is a known phenomenon that is difficult to analyse precisely. The purpose of this study was to present a non-invasive method for locating and quantifying sorption phenomena using radiopharmaceuticals. Radiopharmaceutical are medicines armed with a radionuclide enabling quantification and imaging using dedicated scanners. The sorption of nine different radiopharmaceuticals on 2- and 3-part syringes was investigated. These syringes were filled with the studied radiopharmaceutical solutions and stored immobile for 3 h. At different times ranging from 0 to 180 min, 10 µL were taken from the syringes and the radioactivity of these samples was determined by a gamma counter. 5 radiopharmaceuticals exhibited no significant sorption at any time point in both 2 and 3-parts syringes, but 4 radiopharmaceuticals exhibited sorption losses varying from 20 to 33% after 3 h contact with 3-part-syringes, but no sorption on 2-part syringes at any time point. [99mTc]Tc-tetrofosmine Single Photon Emission Computed Tomography/Computed Tomography imaging indicated clearly that the interactions were located on the rubber plunger of the 3-part-syringes. The specific nature of radiopharmaceuticals allowed their use as an innovative method to quantify and localize drug sorption phenomena.

Attitude of community pharmacists toward patients with a substance-related disorder (heroin, alcohol and tobacco), estimation of harmfulness and knowledge of these substances, and continuing education: A pilot cross-sectional study.

OBJECTIVES: To investigate attitude of community pharmacists toward patients with a substance-related disorder (heroin, alcohol and tobacco). MATERIAL AND METHODS: The attitudes were assessed thanks to the Attitude to Mental Illness Questionnaire (AMIQ) for heroin, alcohol and tobacco-related disorders in three independent groups of pharmacists. Estimation of substance-related harmfulness, knowledge of substance-related disorders and activities/needs for continuing education on substance-related disorders were also recorded. RESULTS: Thirty-five pharmacists were included (heroin: 11, alcohol: 10 and tobacco: 14). AMIQ scores for heroin-related disorder were negative and lower than for alcohol (P<0.01) and tobacco (P<0.001). AMIQ scores for alcohol-related disorder were lower than for tobacco (P<0.05). The estimation of heroin-related harmfulness was higher than for alcohol and tobacco (P<0.001). The estimations of knowledge of substance-related disorders were lower for opioid and alcohol than for tobacco (P<0.001). AMIQ scores and the needs for continuing education on each associated addiction showed a positive relation (P<0.01). CONCLUSION: Pharmacists had a negative attitude toward heroin and alcohol-related disorders. A positive attitude toward patients with a substance-related disorder was associated with a need for continuing education. Efforts should be made to change attitudes and to promote continuing education on heroin and alcohol-related disorders.

[Infusion sets in neonatology: What practices in France?] / Montages de perfusion en néonatologie : quelles pratiques en France ?

OBJECTIVES: Therapeutic management of ill newborns can require complex infusion practices using medical devices (MD). Currently, there does not exist any recommendations concerning these infusion practices. The objective of this work was to study and characterise French infusion methods neonatal and neonatal intensive care units. MATERIALS AND METHODS: The study was performed in 2019, during 6 months. French hospitals possessing high (type 3) or medium (type 2B) grade maternity ward were contacted and asked to complete a 5 part online survey, to gather general information about the hospital/ward, infusion methods (overall and detailed), and detailed information about the medications and MD used. RESULTS: The participation level was of 19.6 % Type 3 maternities use overall two-times more MD than those of type 2B. The vascular access device most commonly used was a single lumen catheter (80.6 % of infusion methods). 100 % of the hospitals having answered used multi-access devices (three-way tap, multiport infusion manifold, Y-extension lines) and 93.5 % used a pump-infusor. Lipidic filters for parenteral nutrition were used in 78.6 % of the hospitals. Two general standard of infusion methods were isolated: a simple version with two access points (type 2B hospitals), and a complex one with five access points (from hospitals with type 3 maternities). CONCLUSIONS: Neonatal infusion practices in France are very heterogeneous, thus exposing the patients to a degree of variability during their therapeutic management. This work is a first step forwards to help analyse and anticipate the risks of content/container interactions caused by infusion practices.

On-call duties in hospital pharmacies: National survey and elaboration of a training program for pharmacy residents.

OBJECTIVES: During their residency, pharmacy residents are required to attend a hospital on-call program in order to insure the continuum of care for inpatients. This activity is subject to risks, and requires a prior training. Our aim was to develop and to optimize such a training program. METHODS: To this end, we first established a baseline study of the existing training methods in our hospital and those in the different hospitals of France in which pharmacy residents realize in-house on-call duties, associated with an identification of both pharmacists and students' needs in our institution. These preliminary studies were used to create a transversal, structured and harmonized training program. RESULTS: The results of our national survey highlighted great disparities of training between the establishments and point out the lack of structure, organization and harmonization of the training, which residents expected to be improved. Our training program contains 3 parts: initial theoretical training, initial practical training and continuous training. Beyond the harmonization of the theoretical training's materials between the different sectors of the pharmacy, new tools were introduced like an in-house on-call duty notebook complementary to trainings adapted to note taking, simulation's workshops and interactive quizzes. The training was gradually implemented in our hospital pharmacy, in collaboration with the pharmacists of the different activity sectors. CONCLUSIONS: The next steps of our work will be to assess pharmacists and pharmacy residents' satisfaction about our program and its efficacy.

Impact of alternative materials to plasticized PVC infusion tubings on drug sorption and plasticizer release.

Medical tubings in plasticized polyvinylchloride (PVC) are widely used for the infusion of medications but are known in some cases to cause content-container interactions (drug sorption and plasticizer release). The aim of this study was to assess interactions between drugs and five alternative materials to a reference plasticized PVC intravenous (IV) infusion tubing: three were PVC coextruded with polyethylene (PE), polyurethane (PU) or a thermoplastic elastomer (Styrene-EthyleneButadiene-Styrene (SEBS)) and two were SEBS or thermoplastic olefin (TPO) monolayer tubings. Diazepam and insulin were chosen as respective reference of absorption and adsorption while paracetamol acted as a negative control. The concentration of each drug was quantified with liquid chromatography to evaluate a potential loss after a static contact condition and simulated infusion at 1 mL/h and 10 mL/h dynamic condition by an electric syringe pump. A characterization of each material's surface was performed by Fourier transform infrared spectroscopy in attenuated total reflection mode (ATR-FTIR) and by measurement of surface zeta potential. Plasticizer release was quantified by gas chromatography coupled with mass spectrometry (GC-MS). For all tubings except PVC/PU, no loss of paracetamol was observed in any condition. Diazepam sorption appeared to be less important with PVC/PE, PVC/SEBS, SEBS and TPO tubings than with PVC, but was more important when using PVC/PU tubings. PVC tubings induced the least loss of insulin amongst all the studied materials. Surface analysis by ATR-FTIR highlighted the presence of a plasticizer (that could be attributed to Tris (2-Ethylhexyl) Trimellitate (TOTM)) in the coextruded SEBS layer of PVC/SEBS, which could have influenced drug sorption, probably as a consequence of a migration from the PVC layer. Coextruded PVC/SEBS and PVC/PE presented the lowest zeta potential of all studied materials with respective values of -39 mV and -36 mV and were related to the highest sorption of insulin while PVC/PU with the highest zeta potential (about -9 mV) presented the highest absorption of diazepam. Coextruded layered materials appeared to have a lower plasticizer release than PVC alone. As a conclusion, PVC/PE and thermoplastic elastomers alone or coextruded with PVC could be interesting alternatives to PVC tubings with regards to sorption phenomena and plasticizer release.

Cost analysis of single-use (Ambu® aScope™) and reusable bronchoscopes in the ICU.

BACKGROUND: Flexible optical bronchoscopes are essential for management of airways in ICU, but the conventional reusable flexible scopes have three major drawbacks: high cost of repairs, need for decontamination, and possible transmission of infectious agents. The main objective of this study was to measure the cost of bronchoalveolar lavage (BAL) and percutaneous tracheostomy (PT) using reusable bronchoscopes and single-use bronchoscopes in an ICU of an university hospital. The secondary objective was to compare the satisfaction of healthcare professionals with reusable and single-use bronchoscopes. METHODS: The study was performed between August 2009 and July 2014 in a 16-bed ICU. All BAL and PT procedures were performed by experienced healthcare professionals. Cost analysis was performed considering ICU and hospital organization. Healthcare professional satisfaction with single-use and reusable scopes was determined based on eight factors. Sensitivity analysis was performed by applying discount rates (0, 3, and 5%) and by simulation of six situations based on different assumptions. RESULTS: At a discount rate of 3%, the costs per BAL for the two reusable scopes were 188.86€ (scope 1) and 185.94€ (scope 2), and the costs per PT for the reusable scope 1 and scope 2 and single-use scopes were 1613.84€, 410.24€, and 204.49€, respectively. The cost per procedure for the reusable scopes depended on the number of procedures performed, maintenance costs, and decontamination costs. Healthcare professionals were more satisfied with the third-generation single-use Ambu® aScope™. CONCLUSIONS: The cost per procedure for the single-use scope was not superior to that for reusable scopes. The choice of single-use or reusable bronchoscopes in an ICU should consider the frequency of procedures and the number of bronchoscopes needed.

Stability of an ophthalmic micellar formulation of cyclosporine A in unopened multidose eyedroppers and in simulated use conditions.

Cyclosporine A eye drops are used at concentrations ranging from 0.5 to 20mg/mL to treat a variety of ophthalmic diseases. Cyclosporine A formulations at high concentrations are difficult to manufacture because of cyclosporine's lipophilicity, and generally require an oil based vector. In this study, we investigated the physicochemical and microbiological stability of two high concentrations (10mg/mL and 20mg/mL) of an ophthalmic cyclosporine A micellar solution in a low density polyethylene multidose eyedropper, at two conservation conditions (5°C and 25°C), before and with simulated use. Analyses used were the following: visual inspection, cyclosporine quantification by a stability-indicating liquid chromatography method, osmolality and pH measurements and turbidity. A complementary analysis by dynamic light scattering was implemented to evaluate potential particle formation or micelle size change. In the in-use study, cyclosporine quantification was also performed on the drops emitted from the multidose eyedroppers. Our results show that the cyclosporine micellar formulation retains good physicochemical and microbiological stability, as all parameters stayed within acceptable range limits, however a higher variability in cyclosporine concentrations was observed for 20mg/mL units stored at 25°C. The in-use study showed that cyclosporine concentrations in the emitted drops were also within acceptable range limits. The micellar formulation presented in this study can therefore be stored at 5°C or at ≤25°C for up to 6months.

Analysis of plasticizers in PVC medical devices: Performance comparison of eight analytical methods.

A wide variety of medical devices (MDs) used in hospitals are made of flexible plasticized polyvinylchloride (PVC). Different plasticizers are present in variable amounts in the PVC matrix of the devices and can leach out into the infused solutions and may enter into contact with the patients. The ARMED1 project aims to assess the migration of these plasticizers from medical devices and therefore the level of exposure in patients. For the first task of the project, eight methods were developed to directly detect and quantify the plasticizers in the PVC matrix of the MDs. We compared the overall performances of the analytical methods using standardized and validated criteria in order to provide the scientific community with the guidance and the technical specifications of each method for the intended application. We have shown that routine rapid screening could be performed directly on the MDs using the FTIR technique, with cost-effective analyses. LC techniques may also be used, but with limits and only with individual quantification of the main plasticizers expected in the PVC matrix. GC techniques, especially GC-MS, are both more specific and more sensitive than other techniques. NMR is a robust and specific technique to precisely discriminate all plasticizers in a MD but is limited by its cost and its low ability to detect and quantify plasticizer contamination, e.g. by DEHP. All these results have been confirmed by a real test, called the " blind test " carried out on 10 MD samples.

In vitro evaluation of TiO2 nanotubes as cefuroxime carriers on orthopaedic implants for the prevention of periprosthetic joint infections.

CONTEXT: The prevention of periprosthetic joint infections requires an antibiotic prophylactic therapy, which could be delivered locally using titanium dioxide nanotubes as novel reservoirs created directly on the orthopaedic implant titanium surface. OBJECTIVE: In this study, the influence of several parameters that could impact the use of titanium dioxide nanotubes as cefuroxime carriers was investigated. METHOD: Cefuroxime loading and release was studied for 90 min with three nano-topography conditions (nano-smooth, nano-rugged and nano-tubular), two cefuroxime loading solution concentrations (150 mg/mL and 25mg/mL) and two nano-tubular crystalline structures. RESULTS: In all tested conditions, maximum amount of cefuroxime was obtained within 2 min. For both cefuroxime loading solution concentrations, nano-smooth samples released the least cefuroxime, and the nano-tubular samples released the most, and a six-fold increase in the concentration of the cefuroxime loading increased the amount of cefuroxime quantified by more than seven times, for all tested nano-topographies. However, the nano-tubes' crystalline structure did not have any influence on the amount of cefuroxime quantified. CONCLUSION: The results demonstrated that the surface nano-topography and loading solution concentration influence the efficiency of titanium dioxide nanotubes as cefuroxime carriers and need to be optimized for use as novel reservoirs for local delivery of cefuroxime to prevent periprosthetic infections.