Using simulation to improve pharmacy operators' handling of cytotoxic spills.

INTRODUCTION: International Society of Oncology Pharmacy Practitioners guidelines recommend having standard operating procedures (SOPs) and initial and yearly retraining programs on cytotoxic spill handling for pharmacy operators (POs). This study aimed to create a simulation-based training (SBT) program on this subject and evaluate its impact on POs' real-life performance. METHODS: Randomly formed pairs of POs underwent a 2.5-hour training program, including two simulation exercises (a broken cytotoxic vial on the floor and a leaking cytotoxic bag) in a simulated pharmacy production unit. Each participant applied the cytotoxic spill handling SOPs. The PO and trainer-pharmacist did a debriefing after each exercise. Satisfaction was recorded on a 0-to-100% scale. A 20-item questionnaire assessed general knowledge about cytotoxic spill handling before and after the training. One month before and one month after the training, the POs underwent a real-life test when the trainer broke a fake cytotoxic vial in the cytotoxic storage area. Their performance in applying the SOPs was assessed on a 20-point checklist, and the time to handle the spill was recorded. RESULTS: Twelve POs participated. Mean satisfaction score was 98.9%. Mean knowledge score improved from 10.8/20 (SD = 2.0) before training to 14.5/20 (SD = 1.6) after training (p < 0.05). Mean real-life SOP performance improved from 78.6% (SD = 7.4%) to 97.1% (SD = 5.2%) (p < 0.05). Mean time to handle cytotoxic spills decreased from 17.3 minutes (SD = 3.6 minutes) to 11.9 minutes (SD = 1.5 minutes) (p < 0.05). CONCLUSION: POs improved their knowledge and real-life competencies for handling cytotoxic spills. This training will be included in POs' initial and continuing training programs.

Game-based learning as training to use a chemotherapy preparation robot.

INTRODUCTION: In 2015, our university hospital pharmacy acquired the PharmaHelp robot system to automate part of its chemotherapy production. Complex technical use, downtime periods, and insufficient training caused a drop in motivation and disparities in operators' knowledge. We created a short, playful, standardized, gamed-based training program to address this, and evaluated its impact. METHODS: Operators were classified as trainers or trainees according to their knowledge about Information and Communication Technologies. Before, after the training, and at 6 months (6M), their robot knowledge was assessed on a 0-24-scale, motivation and self-efficacy in using it on 0-to-100 scales. Pairwise comparison t-test with Bonferroni adjustment was used (p < 0.05 considered significant). Satisfaction was measured using a six-point Likert scale. Trainer/trainee teams participated in 2-hour training sessions with three games and a debriefing. For "Knowing the manufacturing steps," cards with the steps were placed in the correct order. For "Knowing the criteria for using the robot," teams guessed whether certain compounds could be used with the robot. For "Knowing how to handle production errors," the answer to each error (taken from real-life issues) was selected from four options. RESULTS: Participants (n = 14) were very satisfied about sessions' interactivity and playfulness. Knowledge improved from 57% pretraining to 77% (p < 0.005) to 76.6% (6M) (p < 0.05 compared to pretraining). Motivation and self-efficacy, respectively, improved from 57.6% to 86.6% (p < 0.05) to 70.4% (6M) and from 48.5% to 75.6% (p < 0.05) to 60.2% (6M) (p > 0.1 compared to pretraining) (t-test). CONCLUSIONS: This highly appreciated training program efficiently improved knowledge retention out to six months.

Game-based training to promote handwashing, handrub and gloving for hospital pharmacy operators.

OBJECTIVES: Adherence to handwashing, handrub and gloving procedures is mandatory for safe, aseptic drug compounding in hospital pharmacies. This study measured participants' satisfaction and effectiveness of a game-based training tool (Handtastic Box) developed to improve adherence. METHODS: Handtastic Boxes were played by pairs of pharmacy operators (introductory video, 1 min study of guidelines, game). In module 1, players watched videos of somebody handwashing and had to find the missing step. They examined wooden models of hands under ultraviolet (UV) light, with some areas stained with fluorescein, to find the hand showing contamination. In module 2, players used a fluorescein hydroalcoholic solution and placed their hands under UV light to highlight missing areas. In module 3, players identified major errors that could compromise glove sterility and linked them to a problem explanation. Then, they applied paint to their fingertips and donned gloves-the paint had to stay inside them. Satisfaction about the training was assessed with a 10-question survey; knowledge about procedures was assessed using a before-and-after questionnaire of nine questions, a 100-point confidence score (modules 1 and 2), and the number of before-and-after errors made during donning gloves (module 3). RESULTS: Operators were very satisfied and felt more competent after training. Average knowledge score increased from 56.3% (SD 18.2%) to 93.7% (SD 9.5%), and confidence in answers increased from 66.4% (SD 18.7%) to 95.7% (SD 5.52%) (n=14, both modules 1 and 2). The mean error score for gloving procedure decreased from 1.7 (SD 0.8%) to 0.3 (SD 0.5%) (n=10, module 3). CONCLUSION: Handtastic Boxes proved to be a highly effective training method for improving knowledge of handwashing, handrub and gloving.

A room of errors simulation to improve pharmacy operators' knowledge of cytotoxic drug production.

INTRODUCTION: We used an educational healthcare simulation tool called room of errors (ROE) to raise pharmacy operators' awareness of potential errors in a chemotherapy production process and assessed its impact on their knowledge and satisfaction. METHODS: Twenty-five errors (compiled from internal procedures, literature and our hospital's reported incidents) were categorised as static (n = 7, visible by the participant anytime) and dynamic (n = 18, made by a pseudooperator in front of the participant). Our simulated cytotoxic production unit (CPU) hosted the 1 h-simulation. Two pharmacists (supervisor/pseudo-operator) welcomed the trainee for a 10-min briefing. During the 20-min simulation, participants watched the pseudo-operator's gestures in a simulated chemotherapy production process. Participants called out each error observed (recorded by the supervisor). A 20-min debriefing followed. ROE's impact on knowledge was measured through participants' answers to a before-and after 18-item questionnaire about CPU's procedures and certainty about answers on a scale (0%-100%). Participants evaluated the training using a satisfaction questionnaire (Likert scale, 1-6). RESULTS: The 14 participants detected 70.4% ± 11.4% of errors. Least-detected errors were "using non-disinfected vials" (42.9%) and "touching syringe plunger" (0%). Critical errors (expired leftovers or glucose instead of sodium chloride) were detected at 57.1%. Knowledge improved from 60.3% to 94.1% (p < 0.001) and certainty from 75.3% to 98.8% (p < 0.001). Participants appreciated this non-judgmental, informative, and original training (satisfaction 95.7%). Some pointed out difficulties settling into the game quickly and visualising static and dynamic errors simultaneously. CONCLUSION: This ROE simulation improved operators' knowledge and certainty. Longer-term testing should be done to measure knowledge retention over time.

Use of simulation for education in hospital pharmaceutical technologies: a systematic review.

OBJECTIVES: Because of the inherent risks facing pharmacy technicians, and consequently also patients, initial and continuing education on hospital pharmaceutical technologies is essential. Simulation is a pedagogical tool now widely used in healthcare education. This study's objectives are to provide an overview of simulation's current place in the field of hospital pharmaceutical technology education, to classify these uses, and to discuss how simulation technologies could be better used in the future. DATA SOURCES: Two pharmacists independently searched PubMed, Embase, and Web of Science on 21 July 2020 and included studies in English or French that used simulation as an educational tool in the field of hospital pharmaceutical technologies, whether in academic teaching or professional practice. DATA SUMMARY: Our search criteria resulted in 6248 articles, of which 24 were assessed for eligibility and 13 included in the qualitative synthesis. Simulation in hospital pharmaceutical technology education is used in three different ways: first, as a playful pedagogical tool, with error-based simulations (cleanrooms and preparation sheets with errors), or game-based simulations (escape games, role-plays, and board games); second, as an electronic tool with virtual reality (virtual cleanrooms and serious games), or augmented reality (3D glasses); finally, to evaluate chemical contamination (fluorescein and quinine tests) and microbiological contamination (media-fill tests) during compounding to periodically requalify pharmacy technicians. CONCLUSION: Further studies, including non-technical skills evaluations, are needed to confirm the usefulness of this innovative technique in training as efficiently as possible actual and future pharmacy professionals.

Parenteral Nutrition Process Management for Newborn and Preterm Infants - A Preliminary Risk Analysis.

BACKGROUND: There are variable practices in the management of the parenteral nutrition (PN) process in hospitals having a neonatal intensive care unit (NICU). In our hospital, PN is prepared partially on the neonatal ward by nurses but also at the central pharmacy by trained pharmacy technicians. A previous study showed a concentration non-conformity of 34% of on-ward PN preparations potentially resulting in under- or overfeeding of the patients. OBJECTIVE: The objectives were to perform preliminary risk analyses (PRA) in preparation for our hospital's transition to universal central pharmacy PN compounding. METHODS: A working group including pharmacists, neonatologists, nurses, and pharmacy technicians performed two PRA. The risks of 9 management steps of the PN process were identified, evaluated, and quoted. A comparison of the number of risks and their criticality index (CI) was conducted. RESULTS: A total of 36 and 39 risks were identified for PN preparation in the NICU and the pharmacy, respectively. For the NICU, ten risks (28%) had an "acceptable" CI, 15 risks (42%) were "under control" and eleven (31%) were defined as "non-acceptable". For the pharmacy, 14 risks (36%) had an "acceptable" CI, 19 risks (49%) were "under control" and six (15%) were defined as "non-acceptable". Risks directly related to the preparation process, including the steps preparation hood, PN preparation and analytical quality control, represented a cumulated CI of 145 for eleven NICU-risks vs 108 for twelve pharmacy risks (-26%). The implementation of immediate improvement measures, eg, an electronic prescription form, reduces the total CI by 5.7% and 2.2% for the NICU and the pharmacy, respectively. CONCLUSION: This PRA highlighted the safety differences between PN preparation in the NICU vs the pharmacy at our institution, and facilitated our moving forward with a process change that should improve the care of our neonatal patients. Nevertheless, long-term improvement measures have to be implemented to further reduce risks related to the PN management process.

New missions of a hospital pharmaceutical technology unit during the COVID-19 pandemic.

The pharmaceutical technology unit of the Geneva University Hospitals played a significant role in the fight against COVID-19 through four different missions: (1) providing enough hydroalcoholic solution at the peak of the pandemic; (2) facing supply chain management issues; (3) adapting the workload to the crisis and, above all, (4) managing the human resources necessary to handle these activities.

Quality and safety of parenteral nutrition for newborn and preterm infants as an on-ward preparation.

BACKGROUND: For newborn and preterm infants, standardised and individual parenteral nutrition (PN) is used. PN preparation is at risk for contamination and dosing errors. The quality of PN is crucial for infants and has a direct impact on their health status and safety. PURPOSE: The aim of this study is to evaluate the physicochemical and microbial quality of PN for newborn and preterm infants prepared on a neonatal ward. METHODS: Sampling of various individual PN prepared by nurses on a neonatal ward was performed. Formulations included maximal four electrolytes, variable dextrose and amino acid concentrations. Depending on the sample volume, up to three quality analyses were performed: (1) test for bacterial endotoxins by kinetic-chromogenic method, (2) sterility according to the European and US Pharmacopoeia, and (3) quantification of electrolytes by capillary electrophoresis and of dextrose by ultraviolet detection after enzymatic reaction of hexokinase. The concentrations obtained were evaluated based on the US and Swiss Pharmacopoeia specifications for compounded preparations and compared to the widened pharmacy specifications. RESULTS: The composition of 86% of the 110 analysed PN prepared by nurses on the neonatal ward corresponded to their medical prescription. 14% were out of the acceptable widened pharmacy ranges. We found no microbial contamination in the samples. All PN were free from endotoxins. CONCLUSION: Component concentrations of PN prepared on wards by nurses differed frequently and significantly from their medical prescription, and the deviation can be critical depending on the component and its mode of action. The sample size is too small to evaluate the microbial contamination.

Stability of N-Acetylcysteine (NAC) in Standardized Pediatric Parenteral Nutrition and Evaluation of N,N-Diacetylcystine (DAC) Formation.

The ESPGHAN/ESPEN/ESPR-Guidelines on pediatric parenteral nutrition (PPN) recommend the administration of the semiessential amino acid (AA) cysteine to preterm neonates due to their biochemical immaturity resulting in an inability to sufficiently synthetize endogenous cysteine. The soluble precursor N-acetylcysteine (NAC) is easily converted into bioavailable cysteine. Its dimer N,N-diacetylcystine (DAC) is almost unconvertable to cysteine when given intravenously resulting in a diminished bioavailability of cysteine. This study aims to understand the triggers and oxidation process of NAC to DAC to evaluate possibilities of reducing DAC formation in standardized PPN. Therefore, different air volumes (21% O2) were injected into the AA compartment of a standardized dual-chamber PPN. O2 concentrations were measured in the AA solution and the headspaces of the primary and secondary packaging. NAC and DAC concentrations were analyzed simultaneously. The analysis showed that O2 is principally delivered from the primary headspace. NAC oxidation exclusively delivers DAC, depending on the O2 amount in the solution and the headspaces. The reaction of NAC to DAC being containable by limiting the O2 concentration, the primary headspace must be minimized during manufacturing, and oxygen absorbers must be added into the secondary packaging for a long-term storage of semipermeable containers.

Learning good manufacturing practices in an escape room: Validation of a new pedagogical tool.

INTRODUCTION: Chemotherapies are handled using Good Manufacturing Practices, which ensure asepsis and high-quality production. Continuous education is compulsory and usually includes theoretical and practical exercises. OBJECTIVES: This work aimed to validate an innovative method of teaching good manufacturing practices based on an escape room mixing simulation and gaming. METHOD: Pairs of learners were locked in a simulated clean room (Esclean Room) and had 1 hour to produce a chemotherapy and escape by finding solutions to 23 "Good Manufacturing Practices mysteries" linked to combination locks. To measure the experiment's impact on teaching, questionnaires including the 23 mysteries (in different orders) were filled in before, just after and one month after escape from the Esclean Room. Pharmacy staff' degrees of certainty were noted for each question. A satisfaction survey was completed. RESULTS: Seventy-two learners (29% senior pharmacists, 14% junior pharmacists, and 57% pharmacy technicians) escaped the Esclean Room and 56 answered every questionnaire. The educational intervention resulted in increases in correct answers and certainty. Correct answers rose from 57% in the first questionnaire to 80% in the third (p < 0.001). Certainty scores rose from 50% before the experiment to 70% one month afterwards (p < 0.001). Despite 68% of learners having never taken part in an escape room game before, 79% liked this educational method. CONCLUSION: This study built and tested a pedagogical escape room involving a high risk, professional, pharmacy process. The use of this pharmacy technology simulation had a positive impact on pharmacy staff theoretical knowledge.

Work overload is related to increased risk of error during chemotherapy preparation.

PURPOSE: Chemotherapy preparation units face peaks in activity leading to high workloads and increased stress. The present study evaluated the impact of work overloads on the safety and accuracy of manual preparations. METHOD: Simulating overwork, operators were asked to produce increasing numbers of syringes (8, 16, and 24), with markers (phenylephrine or lidocaine), within 1 h, in an isolator, under aseptic conditions. Results were analyzed using qualitative and quantitative criteria. Concentration deviations of < 5%, 5%-10%, 10%-30%, and >30% from the expected concentration were considered as accurate, weakly accurate, inaccurate, and wrong concentrations, respectively. RESULTS: Twenty-one pharmacy technicians and pharmacists carried out 63 preparation sessions (n = 1007 syringes). A statistically significant decrease in the manufacturing time for one syringe was observed when workload increased (p < 0.0001). Thirty-nine preparation errors were recorded: 30 wrong concentrations (deviation > 30%), 6 mislabeling, 2 wrong diluents, and 1 wrong drug. There was no statistically significant difference in the mean concentration accuracy of final preparations across the three workloads. The overall error rate increased with the number of preparations made in 1 h: 1.8% for 8 preparations, 2.7% for 16 preparations, and 5.4% for 24 preparations (p < 0.05). CONCLUSION: Although pharmacy technicians and pharmacists were able to increase production speeds with no effect on mean concentration accuracy under stressful conditions, there were greater probability errors being made. These results should encourage actions to spread workloads out over the day to avoid peaks in activity.

Reliability of chemotherapy preparation processes: Evaluating independent double-checking and computer-assisted gravimetric control.

Background and objectives Centralized chemotherapy preparation units have established systematic strategies to avoid errors. Our work aimed to evaluate the accuracy of manual preparations associated with different control methods. Method A simulation study in an operational setting used phenylephrine and lidocaine as markers. Each operator prepared syringes that were controlled using a different method during each of three sessions (no control, visual double-checking, and gravimetric control). Eight reconstitutions and dilutions were prepared in each session, with variable doses and volumes, using different concentrations of stock solutions. Results were analyzed according to qualitative (choice of stock solution) and quantitative criteria (accurate, <5% deviation from the target concentration; weakly accurate, 5%-10%; inaccurate, 10%-30%; wrong, >30% deviation). Results Eleven operators carried out 19 sessions. No final preparation (n = 438) contained a wrong drug. The protocol involving no control failed to detect 1 of 3 dose errors made and double-checking failed to detect 3 of 7 dose errors. The gravimetric control method detected all 5 out of 5 dose errors. The accuracy of the doses measured was equivalent across the control methods ( p = 0.63 Kruskal-Wallis). The final preparations ranged from 58% to 60% accurate, 25% to 27% weakly accurate, 14% to 17% inaccurate and 0.9% wrong. A high variability was observed between operators. Discussion Gravimetric control was the only method able to detect all dose errors, but it did not improve dose accuracy. A dose accuracy with <5% deviation cannot always be guaranteed using manual production. Automation should be considered in the future.

Compatibility of intravenous medications with parenteral nutrition: in vitro evaluation.

BACKGROUND AND AIM: Hospitalized patients requiring parenteral nutrition (PN) often need to receive intravenous (IV) medications as well. Y-site administration is occasionally necessary, but physicochemical incompatibilities can occur between the medications and PN. The aim of the present study was to assess the physical compatibility between 25 frequently coadministered IV medications and a commercially available ready-to-use total PN. METHODS: PN (NuTRIflex Lipid Special; B. Braun Medical AG, Sempach, Switzerland) and medications were mixed in 1:1 (v/v) proportions, and the stability was assessed at the time of mixing and after 1 and 4 hours. The stability of lipid emulsion was observed by microscopic investigation, visual inspection, dynamic laser light scattering, and laser light obscuration. The binary admixtures of PN (without lipid emulsion) and medications were used to detect discoloration, visibly detectable precipitates, and subvisual particles. RESULTS: Two of 25 medications were incompatible with the lipid emulsion (serum albumin 20% and tropisetron), 2 showed signs of degradation (discoloration) over time (esomeprazole and pantoprazole), and 1 precipitated at high concentrations (5-fluorouracil). The other 20 medications were considered compatible when administered by Y-site. CONCLUSION: The present study validated the compatibility of 1 commercially available PN and 20 medications. These results offer new solutions to support the implementation of complex therapeutic schemes in practice, when coadministration via Y-site cannot be avoided.

Multiple-test assessment of devices to protect healthcare workers when administering cytotoxic drugs to patients.

PURPOSE: Evaluation of containment safety devices designed and introduced to protect preparers and administrators of hazardous drugs, through a multiple-test assessment. METHODS: Six devices were compared: (1) Kis1 gravity-fed infusion set (Doran International, France), (2) Tevadaptor Spike Port Adapter (Teva Pharma AG, France), (3) Phaseal Infusion Adapter C100 (Carmel Pharma AB, France), (4) Codan Connect Z (Codan, France), (5) Pchimx with or without a cap (Doran International, France), and (6) Clave extension set 011-H1225 with or without Spiros (Hospira, France). Assessment of exposure to hazardous drugs was performed using quinine as fluorescent marker. Mechanical tests included tightness, tension tests, and estimation of the force required to connect the infusion device to the bag. Ergonomic tests were performed by six pharmaceutical technicians. Microbiological contamination was tested with media-fill, on connected bag. RESULTS: No cytotoxic contamination was detected when using Phaseal, Tevadaptor or the Clave extension set with Spiros, Pchimx with a cap or Connect Z devices. For mechanical tests, all devices complied with the norm. Microbiological growth was observed neither in bags nor in tubings. The ergonomic study revealed differences between the devices for potential cytotoxic contamination risk only, but not for handling. CONCLUSIONS: The use of containment safety devices offers improved handling conditions of hazardous compounds. As this study takes various selection criteria into account, its results offer assistance in choosing the most suitable device.

Maximizing calcium and phosphate content in neonatal parenteral nutrition solutions using organic calcium and phosphate salts.

BACKGROUND: The provision of high amounts of calcium and phosphate in parenteral nutrition (PN) solution for neonates is important for bone mass accretion. Because of the risk of calcium phosphate precipitation, a well-documented incompatibility for inorganic salts, the concentrations of these electrolytes in PN are generally limited to 5 mmol/L. The aim of this study was to assess the risk of precipitation of calcium phosphate when organic calcium and phosphate salts are used instead of inorganic salts. METHODS: Precipitation curves were determined for inorganic and organic calcium and phosphate salts in a PN solution favorable to precipitation (low concentration of amino acids and glucose) using visual inspection and particle counts. RESULTS: The use of organic phosphate salt was associated with a decreased risk of precipitation of calcium phosphate. No precipitation occurred up to a concentration of 50 mmol/L of calcium and phosphate. In contrast, organic calcium salt only slightly decreased the risk of precipitation. CONCLUSION: Up to 50 mmol/L of organic calcium and phosphate salts can be safely mixed in PN, even in unstable conditions, making it possible to follow the current European recommendations for requirements in neonates.

Long-term physico-chemical stability of standard parenteral nutritions for neonates.

BACKGROUND & AIMS: Two ready-to-use parenteral nutritions (PN) have been developed, for the first days of life of the premature newborn, along with syringes of lipid emulsion with or without vitamins. Long-term physico-chemical stability for storage in wards was assessed. METHODS: Physico-chemical stability of PN: visual inspection, particle size, pH, osmolarity measurement, amino acids, glucose, and electrolytes dosages. Physico-chemical stability of lipid emulsion: visual inspection, globule size, peroxide level and vitamins A, E, and C dosages. Stability was studied for 12 weeks on refrigerated (2-8 °C) and room temperature (30 ± 2 °C) samples. RESULTS: No precipitation was detected in any PN. A brown coloration was observed in PN stored for four weeks at room temperature but not in the refrigerator. Concentrations of all the nutrients remained constant over the 12 week-study period. Phase separation of the lipid emulsion occurred after three weeks, but particle size complied with the USP limits for 12 weeks. Peroxide content increased only in the samples without vitamins at room temperature. Vitamins remained stable for one week under refrigeration. CONCLUSION: The PN did not present a detectable change of the tested properties when refrigerated for 12 weeks. The lipid emulsion with vitamins is stable for one week when refrigerated.

Determination of potassium, sodium, calcium and magnesium in total parenteral nutrition formulations by capillary electrophoresis with contactless conductivity detection.

A simple method based on capillary electrophoresis with a capacitively coupled contactless conductivity detector (CE-C(4)D) was developed for the determination of potassium, sodium, calcium and magnesium in parenteral nutrition formulations. A hydro-organic mixture, consisting of 100 mM Tris-acetate buffer at pH 4.5 and acetonitrile (80:20, v/v), was selected as the background electrolyte. The applied voltage was 30 kV, and sample injection was performed in hydrodynamic mode. All analyses were carried out in a fused silica capillary with an internal diameter of 50 microm and a total length of 64.5 cm. Under these conditions, complete separation between all cations was achieved in less than 4 min. The CE-C(4)D method was validated, and trueness values between 98.6% and 101.8% were obtained with repeatability and intermediate precision values of 0.4-1.3% and 0.8-1.8%, respectively. Therefore, this method was found to be appropriate for controlling potassium, sodium, calcium and magnesium in parenteral nutrition formulations and successfully applied in daily quality control at the Geneva University Hospitals.