Augmented Reality Eyewear for Assisting in the Preparation and Control of Cancer Therapies: Assessing the Learning Curve and Level of Adoption.

Since March 2022, the centralized cytotoxic preparation unit at the Lille University Hospital (Lille, France) is equipped with augmented reality eyewear for preparation and quality control. The technology enables a user-friendly guided step by step preparation process. It also assists the user by identifying vials through data matrix scan and recording photos at different stages of preparation in order to replace the in-process double visual inspection which will now be carried out a posteriori during the release control. In this paper, we evaluate user feedback and model the learning curve for this new tool. The team's feedback was evaluated using the System Usability Scale (SUS) and Short User Experience Questionnaire (S-UEQ). Both questionnaires showed very good acceptance of the tool by our teams, with scores of 79.7 for the SUS and 2.014 for the UEQ. Finally, a learning curve was drawn up according to Wright, showing a learning curve of 91%. This study shows that the tool has been very well integrated into our preparation unit.

[Use of a pharmaceutical decision support system in the valuation of hospital stays: Evaluation through 3 examples in collaboration with the department of medical information]. / Utilisation d'un système d'aide à la décision pharmaceutique dans la valorisation des séjours hospitaliers : évaluation à travers 3 exemples en collaboration avec le département de l'information médicale.

Pharmacy decision support systems (PDSS) help clinical pharmacists to prevent and detect adverse drug events. The coding of hospital stays by the department of medical information (DMI) requires expertise, as it determines hospital revenues and the epidemiological data transmitted via the French national hospital database. The aim was to study the interest and feasibility of using a PDSS, in collaboration with the DMI, to help with the coding of hospital stays. Over 5 months, three rules were implemented in the PDSS to detect gout, Parkinson's disease and oro-pharyngeal candidiasis. The PDSS alerts were analyzed by a pharmacy resident and then forwarded to the DMI, who analyzed the stays to see whether or not the coding for the disease corresponding to the alert was present. The absence of coding was evaluated and tracked, along with the resulting change in severity and valuation. Three hundred and ninety-nine alerts from the PDSS were analyzed and sent to the DMI, representing 211 stays and 309 uniform hospital standardized discharge abstract (UHSDA) in the fields of medicine, surgery and obstetrics. Two hundred and eight (67.3%) UHSDA did not have the coding corresponding to the alert. For the majority of these UHSDAs, apart from diagnostic precision, there was no impact on the valuation of stays. For 4 UHSDAs, the addition of the diagnosis code led to an increase in the value of the stay and the severity of the homogeneous patient groups. The total revaluation corresponding to this modification was €5416. The use of PDSS has helped in the precision of diagnosis coding and the valuation of stays. This result must be weighed against the time invested in analyzing alerts and associated coding. An improvement in disease detection and data processing is needed to be feasible in practice, given the more than 227,600 RSS performed per year at our facility.

Impact of the use of a drug-drug interaction checker on pharmacist interventions involving well-known strong interactors.

OBJECTIVES: Several drug-drug interaction (DDI) checkers such as DDI-Predictor have been developed to detect and grade DDIs. DDI-Predictor gives an estimate of the magnitude of an interaction based on the ratio of areas under the curve. The objective of the present study was to analyse the frequencies of DDIs involving well-known strong interactors such as rifampicin and selective serotonin reuptake inhibitors (SSRIs), as reported by a clinical pharmacy team using DDI-Predictor, and the pharmacist intervention acceptance rate. METHODS: The pharmacist intervention rate and the physician acceptance rate were calculated for DDIs involving rifampicin or the SSRIs fluoxetine, paroxetine, duloxetine and sertraline. The rates were compared with a bilateral χ2 test or Fisher's exact test. RESULTS: Of the 284 DDIs recorded, 38 (13.4%) involved rifampicin and 78 (27.5%) involved SSRIs. The pharmacist intervention rate differed significantly (68.4% for rifampicin vs 48.8% for SSRIs; p=0.045) but the physician acceptance rate did not (84.6% for rifampicin vs 81.6% for SSRIs; p=1). Pharmaceutical interventions for SSRIs were more frequent when the ratio of the area under the drug concentration versus time curve in DDI-Predictor was >2. Pharmacists were more likely to issue a pharmacist intervention for DDIs involving rifampicin because of a high perceived risk of treatment failure and were less likely to issue a pharmacist intervention for DDIs involving an SSRI, except when the suspected interaction was strong. CONCLUSIONS: DDI checkers can help pharmacists to manage DDIs involving strong interactors. DDIs involving strong inhibitors versus a strong inducer differ with regard to their intervention and acceptance rates, notably due to the estimation of the magnitude of the DDI.

The Infusion of Piperacillin/Tazobactam with an Elastomeric Device: A Combined 24-H Stability Study and Drug Solution Flow Rate Analysis.

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 <10% degradation and a flow rate within ± 15% of the nominal value over the 24-h infusion period: all three P/T solutions were found to be stable. The actual flow rate was lower than the expected flow rate; this difference was probably due to the drug solution's high viscosity and must be taken into account in clinical use.

A prospective, single-centre study of the feasibility of the use of augmented reality for improving the safety and traceability of injectable investigational cancer drug compounding.

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.

[Monitoring student skills during community pharmacy placements: Retrospective analysis of dashboards]. / Suivi des compétences des étudiants au cours du stage de pratique professionnelle en pharmacie officinale : analyse rétrospective des tableaux de bord.

OBJECTIVES: The aim of this work is to describe the skills considered to have been acquired by students during their professional practice placements, with particular emphasis on skills related to the new roles of pharmacists. METHODS: Skills are monitored during the professional practice placement using the dashboard included in the guide designed by the college of community pharmacy placement supervisors. Each skill is assessed at three points during the placement. The assessment is carried out jointly by the student and his or her placement supervisor using the dashboard, which is available online in the form of a form on the Moodle platform. We conducted a retrospective analysis of the professional practice placement dashboards for the 2018-2019 to 2022-2023 academic years. RESULTS: The response levels for the three phases of the dashboard are very high, always exceeding 90% of students completing their placement. All of the scorecards show a progression in the acquisition of skills throughout the placement and enable certain skills to be distinguished in terms of their level of acquisition at the end of the placement. The focus on pharmaceutical interviews shows that the rate of acquisition of this skill is over 85% in 2021 and 2023, the years in which the subject of the public health project was the performance and quality assurance of pharmaceutical interviews in pharmacies, whereas it is no higher than 38% in the other years. CONCLUSIONS: Our work shows the contribution of the professional practice placement dashboard in monitoring student progress. The analysis carried out reveals different levels of mastery at the start of the placement and different levels of progress depending on the skills. It also reveals the contribution made by the intervention on the content of the placement, particularly in terms of the acquisition of certain skills, especially those related to new tasks such as conducting pharmaceutical interviews.

Pharmaceutical Decision Support System Using Machine Learning to Analyze and Limit Drug-Related Problems in Hospitals.

The health product circuit corresponds to the chain of steps that a medicine goes through in hospital, from prescription to administration. The safety and regulation of all the stages of this circuit are major issues to ensure the safety and protect the well-being of hospitalized patients. In this paper we present an automatic system for analyzing prescriptions using Artificial Intelligence (AI) and Machine Learning (ML), with the aim of ensuring patient safety by limiting the risk of prescription errors or drug iatrogeny. Our study is made in collaboration with Lille University Hospital (LUH). We exploited the MIMIC-III (Medical Information Mart for Intensive Care) a large, single-center database containing information corresponding to patients admitted to critical care units at a large tertiary care hospital.

Retrospective comparison of a weight-based dose every 2 weeks with a fixed dose every month: a real-life analysis of nivolumab in the treatment of advanced melanoma.

Nivolumab was first authorized at a weight-based dose (WBD) of 3 mg/kg every two weeks (Q2W). Since 2017, a fixed dose (FD) regimen [first 240 mg Q2W and then 480 mg per month (Q4W)] was allowed. The objective of the study was to compare a WBD regimen and an FD regimen with regard to effectiveness and safety. We conducted a single-center, retrospective, real-life study of consecutive adult patients who had received a WBD of nivolumab or an FD of 480 mg Q4W. The primary endpoint was the occurrence of grade ≥3 immune-related adverse events (irAEs). The secondary endpoints were overall survival and cost of the treatment. In all, 342 patients were included: 71 in the WBD cohort and 271 in the FD cohort. Of these patients, 201 patients (59.6%) experienced an irAE, and 24 of these events were graded as ≥3. At 12 months, there was no significant difference in irAE occurrence between the two cohorts [hazard ratio (95% confidence interval): 0.54 (0.21-1.36), P  = 0.19]. The 12-month overall survival rate was significantly lower in the WBD cohort ( P  < 0.001). Switching from a fortnightly weight dose to a fixed monthly dose halves the cost of hospitalization. Our results did not show a significant difference between WBD and FD cohort in the occurrence of severe irAEs. However overall survival appeared to be significantly higher in FD group. Some clinical trials are investigating a hybrid dosing regimen in which a WBD is capped by an FD. The present results need to be confirmed in prospective studies.

Implementation of a clinical decision support system for the optimization of antidiabetic drug orders by pharmacists.

AIMS: The objective of the study was to describe the impact of a clinical decision support system (CDSS) on antidiabetic drug management by clinical pharmacists for hospitalized patients with T2DM. METHODS: We performed a retrospective, single-centre study in a teaching hospital, where clinical pharmacists analysed prescriptions and issued pharmacist interventions (PIs) through a computerized physician order entry (CPOE) system. A CDSS was integrated into the pharmacists' workflow in July 2019. We analysed PIs during 2 periods of interest: one before the introduction of the CDSS (from November 2018 to April 2019, PIs issued through the CPOE alone) and one afterwards (from November 2020 to April 2021, PIs issued through the CPOE and/or the CDSS). The study covered nondiabetology wards as endocrinology, diabetes and metabolism departments were not computerized at the time of the study. RESULTS: There were 203 PIs related to antidiabetic drugs in period 1 and 319 in period 2 (a 57.5% increase). Sixty-four of the 319 PIs were generated by the CDSS. Noncompliance/contraindication was the main problem identified by the CDSS (41 PIs, 68.4%), and 57.8% led to discontinuation of the drug. Most of the PIs issued through the CDSS corresponded to orders that had not been flagged up by clinical pharmacists using the CPOE. Conversely, most alerts about indications that were not being treated were detected by the clinical pharmacists using the CPOE and not by the CDSS. CONCLUSION: Use of CDSS by clinical pharmacists improved antidiabetic drug management for hospitalized patients with T2DM. The CDSS might add value to diabetes care in nondiabetology wards by decreasing the frequency of potentially inappropriate prescriptions and adverse drug reactions.

Medication exposure of the dyad patient-caregiver in Alzheimer's disease and related dementias: a cross-sectional study.

BACKGROUND: Patients with Alzheimer's disease and related dementias and their caregivers can be defined as people with higher risk of developing medication-related problems due to aging and polypharmacy. AIM: To assess the medication exposure of patient with Alzheimer's disease and related dementias and their caregivers. METHOD: Ancillary cross-sectional study based on baseline medication data of the PHARMAID RCT. The PHARMAID study was a multi-center RCT assessing an integrated pharmaceutical care at a psychosocial program. Older outpatients with Alzheimer's disease and related dementias and their older caregivers were eligible for inclusion. Baseline medication data were used to assess the medication exposure, illustrated by the number of medications, the prevalence of potentially inappropriate medications (PIMs) using the EU(7)-PIM list and the Medication Regimen Complexity Index (MRCI). RESULTS: Seventy-three dyads were included in this ancillary study. The mean numbers (SD) of medications used by patients was 6.8 (2.6) and by caregivers was 4.7 (3.7). Overall, 60.3% of patients used at least one PIM and 47.9% of caregivers. Regarding the medication regimen complexity, the mean MRCI was 16.3(8.1) for patients and 11.3(10.5) for caregivers. CONCLUSION: The results of this study confirm the relevance of carrying out medication review with patients, but also with their caregivers who can be considered as hidden patients.

Evaluation of cancer drug infusion devices prior to the implementation of a compounding robot.

INTRODUCTION: Compounding robots are increasingly being implemented in hospital pharmacies. In our hospital, the recent acquisition of a robot (RIVATM, ARxIUM) for intravenous cancer drug compounding obliged us to replace the previously used infusion devices. The objective of the present study was to assess and qualify the new intravenous sets prior to their use in our hospital and prior to the implementation of the compounding robot. MATERIALS AND METHODS: The ChemoLockTM (ICU Medical) was compared with the devices used previously for compounding (BD PhaSealTM, Becton-Dickinson) and infusion (Connect-ZTM, Codan Medical). The connection/disconnection of infusion devices to/from 50 mL infusion bags was tested with a dynamometer (Multitest-i, Mecmesin). Leakage contamination was visualized by a methylene blue assay and was quantified in simulated pump infusions with 20 mg/mL quinine sulfate (N = 36/group); after the analytical assay had been validated, quinine was detected by UV-spectrophotometry at 280 and 330 nm. Groups were compared using chi-squared or Mann-Whitney U tests. RESULTS: The connection/disconnection test showed that although all the devices complied with the current standard, there was a statistically significant difference in the mean ± standard deviation compression force (51.5 ± 11.6 for the Connect-ZTM vs. 60.3 ± 11.7 for the ChemoLockTM; p = 0.0005). Leaks were detected in 32 (29.1%) of the 110 tests of the ChemoLockTM. The contamination rates were also significantly different: 13.9% for the BD PhaSealTM versus 75.0% for the ChemoLockTM; p < 0.0001). DISCUSSION/CONCLUSION: Our results showed that the new infusion device complied with current standards. However, the presence of contamination emphasizes the need for operators to use the recommended personal protective equipment. Further studies of contamination with cancer drugs are required.

Acute stroke in patients taking an oral anticoagulant: impact of clinical pharmacist's intervention on pharmacovigilance reporting.

INTRODUCTION: Ischemic or hemorrhagic stroke can occur to patients treated with oral anticoagulants (OAC), through lack of effectiveness or overdosing. OBJECTIVE: To evaluate the impact of clinical pharmacist's intervention on pharmacovigilance (PV) reporting for OAC-treated patients hospitalized for stroke. METHODS: Monocentric prospective study in which a clinical pharmacist's intervention was performed in a stroke unit, with a focus on patients treated by OAC prior admission. A PV report was made with all data collected for cases of stroke suspected to be related to OAC therapy. Data provided by pharmacist were compared with data initially available in the patient's electronic medical records. PV reports with pharmacist intervention were compared to those without. RESULTS: During the study period, 48 patients were included in the study: 43 (89.6%) ischemic strokes with an embolic or unknown etiology, four hemorrhage strokes (8.33%), and one medication error (2.08%). A clinical pharmacist intervention was performed for 19 patients (39.6%) and provided significant additional data in all of them (100%). The information was related to adherence to treatment for 17 cases (89.5%), OAC's initial prescription date for 11 cases (57.9%) and identifying event(s) that could have interfered with the efficacy of the OAC in five cases (26.3%). For patients with pharmacist intervention, PV reports were significantly more informative in terms of date's introduction of anticoagulant, adherence to treatment, reference to weight change or concomitant event. CONCLUSIONS: clinical pharmacist's intervention with patients taking oral anticoagulants and hospitalized for acute stroke contributes to collect high-quality data for pharmacovigilance reporting.

Limitation of the migration of plasticizers from medical devices through treatment with low-pressure cold plasma, polydopamine coating, and annealing.

Poly(vinyl chloride) (PVC) is widely used in the manufacture of medical devices. The plasticizers added to PVC are potentially toxic for humans, likely to migrate, and thus unintentionally administered to patients. The objective of the present study was to reduce the migration of plasticizer (1,2-cyclohexanedicarboxylic acid, diisononylester (DINCH) or trioctyltrimellitate (TOTM)) from PVC by implementing a three-step surface treatment process: (i) pretreatment with low-pressure argon cold plasma, (ii) polydopamine coating, and (iii) post-treatment with cold plasma exposure or thermal treatment at 140 °C. Samples were then characterized in terms of the water contact angle (WCA) and the aspect in scanning electron microscopy. Plasticizer migration (n = 5) was measured using an HPLC technique with ultraviolet detection and found to depend on the treatment and the plasticizer. Plasticized PVC was hydrophobic, with a measured mean ± standard deviation WCA of 96.7 ± 3.6° for PVC-DINCH and 110.2 ± 5.8° for PVC-TOTM. Plasma post-treatment and thermal post-treatment were respectively associated with a mean decrease in migration of 38.3 ± 1.9% for DINCH and 61.5 ± 4.4% for TOTM. Our results are promising with regard to limiting the migration of plasticizers into the patient's blood and thus enabling the development of safer medical devices.

Evaluation of Strategies for Reducing Vancomycin-Piperacillin/Tazobactam Incompatibility.

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.

Impact of pharmaceutical care integrated at a psychosocial intervention to reduce caregiver's burden in Alzheimer's disease or related dementias: Negative results at 18 months and difficulties to conduct PHARMAID RCT.

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.

Migration of di(2-ethylhexyl) phthalate, diisononylcyclohexane-1,2-dicarboxylate and di(2-ethylhexyl) terephthalate from transfusion medical devices in labile blood products: A comparative study.

BACKGROUND AND OBJECTIVES: Polyvinyl chloride (PVC) plasticized with di(2-ethylhexyl) phthalate (DEHP) is a widely used material for medical transfusion devices. Not covalently bound to PVC, DEHP can migrate into blood products during storage. Recognized as an endocrine disruptor and raising concerns about its potential carcinogenicity and reprotoxicity, DEHP is gradually being withdrawn from the medical device market. Therefore, the use of alternative plasticizers, such as diisononylcyclohexane-1,2-dicarboxylate (DINCH) and di(2-ethylhexyl) terephthalate (DEHT), as potential candidates for the replacement of DEHP in medical transfusion devices has been investigated. The purpose of this study was to evaluate the quantity of PVC-plasticizers in the blood components according to their preparation, storage conditions and in function of the plasticizer. MATERIALS AND METHODS: Whole blood was collected, and labile blood products (LBPs) were prepared by the buffy-coat method with a PVC blood bag plasticized either with DEHP, DINCH or DEHT. DINCH and DEHT equivalent concentrations were quantified in LBPs by liquid chromatography-tandem mass spectrometry or coupled with UV and compared to DEHP equivalent concentrations. RESULTS: The plasticizer equivalent concentration to which a patient is exposed during a transfusion depends on the preparation of LBPs as well as their storage conditions, that is, temperature and storage time. At day 1, for all LBPs, the migration of DEHP is 5.0 and 8.5 times greater than DINCH and DEHT, respectively. At the end of the 49 days storage period, the DEHP equivalent concentration in red blood cells concentrate is statistically higher when compared to DINCH and DEHT, with maximal values of 1.85, 1.13 and 0.86 µg/dm2 /mL, respectively. CONCLUSION: In addition to lower toxicity, transfused patients using PVC-DEHT or PVC-DINCH blood bags are less exposed to plasticizers than using PVC-DEHP bags with a ranging exposure reduction from 38.9% to 87.3%, due to lower leachability into blood components.

Detection of Drug-Related Problems through a Clinical Decision Support System Used by a Clinical Pharmacy Team.

Clinical decision support systems (CDSSs) are intended to detect drug-related problems in real time and might be of value in healthcare institutions with a clinical pharmacy team. The objective was to report the detection of drug-related problems through a CDSS used by an existing clinical pharmacy team over 22 months. It was a retrospective single-center study. A CDSS was integrated in the clinical pharmacy team in July 2019. The investigating clinical pharmacists evaluated the pharmaceutical relevance and physician acceptance rates for critical alerts (i.e., alerts for drug-related problems arising during on-call periods) and noncritical alerts (i.e., prevention alerts arising during the pharmacist's normal work day) from the CDSS. Of the 3612 alerts triggered, 1554 (43.0%) were critical, and 594 of these 1554 (38.2%) prompted a pharmacist intervention. Of the 2058 (57.0%) noncritical alerts, 475 of these 2058 (23.1%) prompted a pharmacist intervention. About two-thirds of the total pharmacist interventions (PI) were accepted by physicians; the proportion was 71.2% for critical alerts (i.e., 19 critical alerts per month vs. 12.5 noncritical alerts per month). Some alerts were pharmaceutically irrelevant-mainly due to poor performance by the CDSS. Our results suggest that a CDSS is a useful decision-support tool for a hospital pharmacist's clinical practice. It can help to prioritize drug-related problems by distinguishing critical and noncritical alerts. However, building an appropriate organizational structure around the CDSS is important for correct operation.

Long-term stability of 10 mg/mL dobutamine injectable solutions in 5% dextrose and normal saline solution stored in polypropylene syringes and cyclic-oleofin-copolymer vials.

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.

Medical devices used in NICU: The main source of plasticisers' exposure of newborns.

Phthalates and other plasticisers are extensively used in medical devices (MD) from which they can leach out and lead to potential multiple problems for the patients. This exposure is a major issue because it is associated with reproductive and neurodevelopment disorders. The Neonatal Intensive Care Units (NICU) population is at high risk due to the daily intensive medical interventions, the reduced ability of newborns to remove these contaminants and their higher sensitivity to endocrine disruptors. We conducted a multicentric biomonitoring study to assess and compare the urinary levels of DEHP (di-(2-ethylhexyl)phthalate), DEHTP (di-(2-ethylhexyl)terephthalate) and TEHTM (tri-(2-ethylhexyl)trimellitate) metabolites as biomarkers of this exposure during and after the newborns' stay in NICU. Daily urinary samples were collected in NICU and at discharge from the hospital for each patient. MD sources and exposure factors were also investigated. 508 urinary samples from 97 patients enrolled in centres 1 and 2 (C1/C2) were collected. The exposure of newborns to DEHP was greater than that of DEHTP and TEHTM, with a median concentration of DEHP metabolites (C1:195.63 ng/mL;C2:450.87 ng/mL) respectively 5 to 10 times higher and 57 to 228 times higher than the median concentrations of DEHTP and TEHTM metabolites. The urinary concentrations of DEHP and TEHTM metabolites were significantly lower at discharge than in NICU, with a 18-and 35-fold decrease for DEHP and a 4 and 8-fold decrease for TEHTM, respectively for C1 and C2, but were similar for DEHTP metabolites. MD used for respiratory assistance, infusion therapy,enteral nutrition and transfusion were the main sources of exposure. Smaller gestational age and body weight significantly increased the newborns' exposure. The elevated levels of DEHP metabolites in NICU patients are still alarming. Additional efforts are necessary to promote its substitution in MD by possibly safer alternatives such as TEHTM and DEHTP, particularly when used for the care of newborns.