European journal of hospital pharmacy : science and practice最新文献

Objective: This study aims to evaluate the risk of occupational exposure to hazardous medicinal products (HMPs) when utilising robotic compounding systems for the preparation of antineoplastic sterile medications. Specifically, it assesses the levels of HMPs present on the surfaces of ready-to-use preparations and on the gloves worn by personnel involved in the compounding process.

Methods: The study was conducted over three consecutive days during routine production with a robotic compounding system. Each day, wipe samples were collected from the surfaces of 20 HMPs preparations and from the gloves of the operator involved in the compounding process. Analyses were performed using an Ultra-High Performance Liquid Chromatography (UHPLC) system to detect and quantify 25 commonly used anticancer molecules in hospital pharmacies.

Results: Throughout the study, the robot compounded 60 bags of 19 different drugs, including 5-fluorouracil, bevacizumab, carboplatin, cisplatin, cyclophosphamide, docetaxel, doxorubicin, eribulin, etoposide, gemcitabine, irinotecan, nivolumab, oxaliplatin, paclitaxel, panitumumab, pembrolizumab, pemetrexed, trastuzumab, and vinorelbine. Only negligible amounts of gemcitabine, below the quantification limit (<0.0025 ng/cm²), were detected on the surfaces of 10 out of the 60 bags and on two of the operator's gloves.

Conclusion: The results demonstrate that surface contamination levels of HMPs in robotic compounding are exceedingly low and, in most cases, undetectable. Occupational exposure to HMPs remains consistently below 0.1 ng/cm², a threshold deemed safe according to various studies. These findings assure the safety of compounding personnel and other hospital staff involved in cancer treatment.

Objectives: There have been cases of cardiotoxicity induced by osimertinib in patients with non-small-cell lung cancer (NSCLC). However, limited data exist for a comprehensive cardiotoxicity profile analysis for osimertinib use in NSCLC patients. The aim of this study was to report the entire profile of cardiotoxicities after the initiation of osimertinib in consecutive patients with epidermal growth factor receptor (EGFR) mutation at a single health system.

Methods: The data were retrospectively collected from electronic medical records for all patients who were started on osimertinib for NSCLC at West Virginia University Health System. Prevalence of heart failure (HF), atrial fibrillation, and prolonged QT before and after starting osimertinib were calculated.

Results: This study had 116 participants and the median age was 72 years. The frequency of each new cardiotoxicity was between 6% and 9%, and the overall percentage of patients who had developed any of the four cardiotoxicities while on osimertinib was 19.9%. The median time of follow-up was 477 days and the median time on osimertinib for all patients was 390 days. The strongest risk factor in predicting a new onset cardiac event was hypertension with a hazard ratio (HR) of 6.35 (confidence interval (CI) 1.48 to 27.23, p=0.013) and HR 5.36 (CI 1.23 to 23.39, p=0.025) in univariate and multivariate analysis respectively.

Conclusion: Osimertinib appears to be associated with an increase in cardiac abnormalities. Given the association between this medication exposure and the observed cardiac toxicities, use of osimertinib may entail closer cardiac monitoring of electrocardiogram (ECG) and echocardiogram abnormalities.

Background: Immune-mediated inflammatory diseases (IMIDs) are a group of disorders characterised by acute or chronic inflammation. Adalimumab and infliximab are the cornerstones of their pharmacotherapy. This study aimed to determine whether variations in the volume and citrate content of different subcutaneous adalimumab formulations result in differences in pain perception during administration.

Methods: A retrospective, cross-cohort study was conducted. Patients who had experienced a change in subcutaneous adalimumab formulation in the past year were recruited. Pain perception was evaluated using a visual analogue scale ranging from 1 to 10 points. Patients were assigned to three groups based on the type of formulation change they experienced: reduction in citrate and volume, reduction in volume only or reduction in citrate only. Data were analysed via ANOVA to determine if there were differences in perceived pain among the three patient groups.

Results: A total of 68 patients were included, of whom 39 (57.4%) experienced a reduction in both volume and citrate, 20 (29.4%) experienced only a reduction in volume and 9 (13.2%) experienced only a reduction in citrate. Analysis showed that all three groups experienced a reduction in perceived pain during administration: 2.46±0.24, 0.3±0.57 and 0.66±1.11 points, respectively (p<0.001).

Conclusions: Our results show that in all three scenarios, perceived pain was reduced. If both volume and citrate are reduced, this effect is greater. Therefore, it is recommended to use formulations with the lowest citrate buffer concentration and the lowest possible volume to minimise pain during adalimumab administration.

Purpose: More than 20% of prescription errors in hospitals are due to an incomplete medication history. Medication reconciliation is a solution to decrease unintentional discrepancies between medications taken at home and hospital prescriptions. It is a normalised clinical activity but it is time consuming. Medication reconciliation usually uses three sources of information for an optimised medical synthesis, one of which is the patient. A conversational robot for patients could be a solution to assist. Numerous digital applications are designed for patients and need to be tested for usability, satisfaction, reliability and time saved.

Method: We analysed Max, a conversational robot for patients scheduled for surgery in Toulouse University Hospital, using routinely collected health data in three successive steps. We examined willingness, compliance and patient satisfaction of usability with a Likert questionnaire and measured the time spent with Max and without. Finally, the reliability has been explored.

Results: The three successive observational steps were assessment of willingness and compliance (79 patients), time saved (61 patients) and reliability of the tool (68 patients). 71% agreed to use Max after a telephone call but only 73% of patients completed Max entirely. Max was well received and the overall satisfaction of usability was high for ease of use, readability, relevance and number of questions. Max saved a few minutes by optimised medical synthesis compared with a conventional telephone call. However, the reliability appeared to be lower than the human conventional telephone call. Randomised controlled trials are needed to confirm this feasibility study.

Conclusion: Max was appreciated by patients and appeared to be suitable for assisting pharmacists in medication reconciliation. The tool established the list of treatments taken by the patient at home but reliability appeared to be lower than a conventional telephone call, recommending a 'double check' on the patient's arrival.

Objectives: Critically ill newborn infants often require simultaneous administration of multiple intravenous (IV) solutions through the same catheter lumen, making compatibility of these solutions crucial in neonatal intensive care units (NICUs). This study aimed to investigate the physical compatibility of insulin aspart, lidocaine, alprostadil and vancomycin with individualised two-in-one parenteral nutrition (PN).

Methods: The study was conducted at the hospital pharmacy's drug compounding facility of the University Medical Centre Utrecht. Two PN formulations were prepared with different electrolyte concentrations (PN1 with high electrolytes and PN2 with low electrolytes), each with either 0% or 30% w/v glucose, resulting in four solutions for testing. Each solution was then mixed with the selected IV drugs in a 1:1 ratio. Compatibility was assessed through visible particle testing, pH measurements and subvisible particle testing at multiple time points (T=0, T=1, T=4 hours).

Results: No visible particles were detected in any combinations. However, insulin and lidocaine combinations exceeded the subvisible particle threshold of 6000 particles ≥10 µm per container volume at T=0 hours, with insulin also exceeding the threshold in a specific PN combination at T=4 hours. pH measurements indicated minimal shifts in the PN solutions, suggesting significant buffering capacity.

Conclusion: Alprostadil and vancomycin IV solutions are physically compatible with two individualised neonatal PN solutions, with high as well as low glucose concentrations. Combinations of PN with lidocaine or insulin form subvisible particles, which could have clinical implications if administered in large volumes over extended periods of time. In clinical scenarios where there is no other option but to administer lidocaine or insulin through the same catheter lumen as PN using a Y-site connector, the use of an in-line filter is advised. Our study adds important compatibility data that can guide clinical practice in NICU settings. However, the broader application of these results requires careful consideration of the unique characteristics of each neonatal PN solution and drug combination.

Background: Intravitreal and intracameral administration of melphalan and topotecan (TPT) has shown its efficacy in the treatment of retinoblastoma over the last few years. Due to rapid hydrolysis, melphalan must be administered within the hour following reconstitution. With improved stability at room temperature and reduced ocular toxicity, TPT seems to be a promising candidate for production of prefilled syringes in terms of safety and efficiency of preparation and treatment administration. Due to the lack of TPT stability data, the stability of TPT at 20 µg/mL and 200 µg/mL in prefilled syringes was evaluated in three different storage conditions.

Methods: The stability of TPT in prefilled syringes was assessed via reversed-phase liquid chromatography coupled to a diode array detector analytical platform. The physicochemical stability of TPT in prefilled syringes in both concentrations, stored at 30±2°C with a relative humidity (RH) of 65±5%, 5±3°C, and -20±5°C, was evaluated over 12 months including visual inspection and pH measurement.

Results: TPT solution in syringes at 20 µg/mL and 200 µg/mL was stable at 5±3°C and -20±5°C for up to 12 months, with no precipitate and no significant change in pH and concentration. A TPT-related degradant, 8-methoxy-TPT, was detected at <0.5% only in 30±2°C (65±5% RH) after 3 months.

Conclusion: This study demonstrated that TPT solutions at 20 µg/mL and 200 µg/mL conditioned in BBraun Omnifix syringes could be stored at 5±3°C for 12 months for safe and secure administration to patients.

Objectives: This paper combines the concepts of design thinking and benchmarking in an aseptic manufacturing context. Design thinking is a problem-solving approach that aims to understand user needs, generate ideas, prototypes and test solutions. There are no published examples in the Irish healthcare setting. There are also no national legislative frameworks in Ireland for compounding medicine in unlicensed hospital aseptic compounding units (ACUs). This study aims to apply design thinking principles to the development of a benchmarking process in the absence of existing frameworks.

Methods: A literature review of design thinking research and international best practice guidelines regarding sterile product manufacture documentation was undertaken to develop an initial prototype benchmarking tool. Design thinking principles were implemented by recruiting and empathising with key senior stakeholders (N=5). Semistructured interviews were conducted with these stakeholders to aid the defining, ideation and optimisation of the prototype tool. The optimised tool was then prototyped and tested in practice by end users (N=11), within an Irish ACU. End users were interviewed regarding their experience of using the tool. Transcripts of interviews were coded, and thematic analysis was undertaken to generate overarching themes to support its further development.

Results: The design thinking approach enabled the development of a benchmarking tool, which was optimised by empathising with key stakeholders. Through the process of empathising, defining, ideation, prototyping and testing, a useful benchmarking tool was developed which was deemed appropriate and accepted by its users.

Conclusions: Design thinking provides a platform for collaboration to deliver innovation and drive quality improvement in healthcare settings. The design thinking process was successful in delivering a user-centred tool for documentation procedures in an aseptic unit, which was accepted for use by end users. When exisiting guidleines and regulations are considered, design thinking shows promise as an innovation tool in Irish aseptic units, manufacturing facilities and the wider healthcare context.

Background: Tachyphylaxis is the rapid development of drug tolerance following repeated administration.

Objectives: To evaluate the United States Food and Drug Administration Adverse Event Reporting System (USFDA AERS) data for drugs significantly associated with tachyphylaxis using disproportionality analysis.

Methods: Disproportionality analysis was used for detecting safety signals for identifying drugs associated with tachyphylaxis. Frequentist and Bayesian statistical methods were employed to detect signals, identifying anesthetics, immunosuppressants, antineoplastics, and psychoactive drugs with positive associations.

Results: Data from 29,153,222 reports between 2004 and 2024 were examined, and 242 reports of tachyphylaxis included. Tachyphylaxis was observed with corticosteroids, opioids, antihistamines, psycholeptics, nitroglycerin, antineoplastics, immunosuppressants, sympathomimetics, psychoanaleptics and psycholeptics that are well documented. Tachyphylaxis was also observed with propofol, cisatracurium, oxcarbazepine, and cabergoline emphasizing the need for further investigation. Hospitalization was reported in 16.9% of cases, with 5% leading to disability and 2.5% resulting in death.

Conclusion: While this study provides valuable insights into drug-related tachyphylaxis, limitations such as underreporting and lack of detailed clinical context exist. Future research should focus on understanding underlying mechanisms and developing strategies to mitigate tachyphylaxis in long-term treatments.

Objectives: Acceleration of the haemostasis process after dermatological surgery predominantly relies on mechanical methods, such as the use of sutures or staples. To our knowledge, there is currently no commercialised haemostatic agent for this specific application. Due to the protein precipitation properties of the 50% (w/v) aluminium chloride hexahydrate solution, its physicochemical stability and maintenance of sterility over a 6 month period were assessed.

Methods: Aluminium chloride hexahydrate was dissolved in sterile water to obtain a 50% (w/v) solution, which was subsequently sterilised through filtration. The solution was then placed in brown glass vials and kept at 20-25°C. The physicochemical stability and sterility of the solution were assessed at four different time points (D0, M1, M3 and M6). At each time point, pH and osmolality were measured, the chloride concentration of the sample was evaluated using the Mohr method, and aluminium identification was carried out through a precipitation method. In addition, the sterility of the solution was also assessed at each time point, according to the European Pharmacopoeia method.

Results: The pH, osmolality and chloride concentration values remained stable and were concordant with the expected values throughout the study. Aluminium was identified in each sample. The sterility of the solution was maintained over the study period.

Conclusions: The physicochemical stability and sterility of the 50% (w/v) aluminium chloride hexahydrate solution were maintained for 6 months. These results indicate that the solution can be prepared in advance.