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

Objectives: Medication errors are a leading source of preventable harm in healthcare, affecting approximately 1 in 30 patients, with a substantial proportion resulting in severe outcomes. In response, the European Association of Hospital Pharmacists convened a Special Interest Group (SIG) to propose comprehensive and sustainable strategies for reducing these errors across Europe, employing a systems approach.

Methods: 89 anonymised medication error reports, and empirical data from the SIG members' daily practice, were analysed to identify root causes, classified into system-level and individual errors. Expert subgroups then linked root causes to targeted preventive measures. A literature review was conducted, searching PubMed and Embase databases, to assess existing standards and identify gaps in medication safety practices, which informed the analysis.

Results: Analysis revealed that governance deficiencies and inconsistent implementation of existing legal standards contribute significantly to medication errors. System-level issues, including inadequate oversight, understaffing and insufficient technical infrastructures, along with individual errors from cognitive lapses, were prevalent. The literature review supported these findings and highlighted the variability in medication safety practices across systems, underscoring the importance of strategic improvements in healthcare policies.

Conclusions: Findings highlight the critical need for robust governance, comprehensive policy frameworks and enhanced safety cultures to prevent medication errors. Automation and improved human-machine interfaces are recommended to mitigate active failures and enhance system reliability. This systems-thinking approach, supported by strengthening legislation and better resource allocation, is essential for reducing medication errors and improving patient safety.

Background: Enoxaparin, a low molecular weight heparin, is widely used for venous thromboembolism treatment and prevention. While routine anti-factor Xa (anti-Xa) monitoring is not generally required, it may be valuable in high-risk populations such as patients with obesity or renal impairment.

Objective: To evaluate the impact of clinical variables on therapeutic enoxaparin dosing and assess the effectiveness of anti-Xa monitoring in real-world clinical practice.

Methods: A retrospective, single-centre, descriptive study was conducted in adults admitted to hospital and receiving therapeutic enoxaparin with correctly timed peak anti-Xa measurements (4 hours after dose) between December 2021 and January 2023. Demographic, clinical and dosing data were extracted from medical records. Predictors of peak anti-Xa concentration were identified using multiple linear regression. Dose-concentration correlations were examined overall and by obesity status.

Results: A total of 146 patients were included (mean age 67±12.3 years; 56.2% male; mean body mass index 29.6±7.5 kg/m²; 30.1% with obesity). Enoxaparin dose (p<0.001) and obesity (p=0.007) were independent predictors of peak anti-Xa concentration; renal impairment and critical illness were not. The correlation between dose and concentration was strong in patients without obesity (r=0.56) but weak in those with obesity (r=0.16). Only 46.6% achieved therapeutic concentrations; 40.4% were subtherapeutic and 12.9% supratherapeutic. Among patients with out-of-range values, dose adjustments were made in 67.9%, but follow-up anti-Xa measurement occurred in only 45.3%; 79.2% of these achieved target concentrations.

Conclusion: Obesity significantly influences enoxaparin pharmacokinetics, reducing predictability of anti-Xa concentrations with actual body weight dosing. Targeted anti-Xa monitoring in high-risk groups, particularly patients with obesity, and structured dose-adjustment protocols may improve therapeutic achievement and safety.

Objectives: Enzyme replacement therapy (ERT) with alglucosidase alfa is the cornerstone of treatment for Pompe disease, a rare disorder caused by acid α-glucosidase (GAA) deficiency. Since 2008, home infusions have been provided in the Netherlands. However, the short shelf-life of the ready-to-administer infusions poses challenges for manufacturing and dispensing pharmacies. This study assessed the stability of ready-to-administer alglucosidase alfa infusions by determining enzyme activity and cellular uptake of two concentrations during 11 days of storage.

Methods: Alglucosidase alfa infusions (2 and 4 mg/mL in 0.9% sodium chloride) were prepared and samples were drawn on days 1 to 7 and 11. Enzyme activity was determined using 4-methylumbelliferyl-α-D-glucoside (4MU-αGlc) and glycogen as substrates. Additionally, enzyme uptake in cultured fibroblasts was investigated.

Results: There was no difference in enzyme activity after 11 days as compared with day 1 using 4MU-αGlc (2 mg/mL: 352 vs 331 nmol/h/mL; 4 mg/mL: 657 vs 662 nmol/h/mL) or glycogen (2 mg/mL: 183 vs 176 nmol/h/mL; 4 mg/mL: 352 vs 357 nmol/h/mL). Uptake of alglucosidase alfa in fibroblasts remained stable over 11 days, with activity ranging from 90 to 104 nmol/h/mL at 2 mg/mL and from 233 to 238 nmol/h/mL at 4 mg/mL. Linear regression analysis confirmed no statistically significant association between time and enzyme activity or uptake.

Conclusions: Ready-to-administer alglucosidase alfa infusion in 0.9% sodium chloride at 2-4 mg/mL is stable for 11 days when stored at 2-8°C or -20°C and protected from light. Extending the stability could enhance efficiency and flexibility for infusion preparation and home delivery, while minimising pharmaceutical waste.

Objective: To use the Raman scattering technique to identify precipitating drug substance(s) in situ.

Background: The case originated when a combination of midazolam hydrochloride, clonidine hydrochloride and fentanyl citrate with Numeta G16E was administered in a central venous catheter line. Following an alarm from the syringe pump, a precipitate in the catheter line was visually observed.

Method: The actual catheter line, with the precipitate still inside, was removed from the clinic and brought to the laboratory. Raman spectra of the precipitate, both when still inside the catheter line (in situ) and after removal, were recorded and analysed for similarity using our in-house database. Additionally, to validate the method, dry powders of midazolam, clonidine and fentanyl were mixed in the ratio of ~300:1:1. This tailor-made mixture was subjected to Raman analysis with the aim of validating the ability of the method to identify all components in a mixture, even if some of the components were present only in small amounts.

Results: The precipitate was successfully identified as midazolam. Measuring in situ caused some additional peaks in the Raman spectra, attributed to the plastic of the catheter line. The influence of these additional peaks was eliminated by a two-component search or by demixing the spectra. The spectra of the precipitate indicated no traces of either clonidine or fentanyl. The experimental results were in line with the results from the theoretical calculations. The ability of Raman spectroscopy to identify both midazolam and small amounts of clonidine and fentanyl in a powder mixture was successfully demonstrated by scanning the tailor-made mixture.

Conclusion: Raman spectroscopy in combination with a database was used for rapid and non-invasive bulk identification in situ. However, to confirm or refute small amounts of a second drug substance in the precipitate, a large area scan of the particle on a flat surface is recommended.

Objectives: Unplanned hospital revisits (UHR) among older adults are common and contribute to adverse clinical outcomes, caregiver burden and increased healthcare costs. We aimed to develop and validate a risk prediction model for UHR in older adults to support early identification.

Methods: We conducted a retrospective cohort study, following the TRIPOD statement, using a Flemish linked database combining primary care and national health insurance data. Adults aged ≥75 years with an all-cause hospital admission in 2014 were included. The primary outcome was UHR, defined as emergency department visits or unplanned hospital admissions within 6 months post-discharge. We used multivariable logistic regression to identify predictors for UHR and develop a risk prediction model. Model performance was assessed using balanced accuracy. Missing data were handled using multiple imputation by chained equations. The model was validated on a held-out test set and a k-nearest neighbour classifier was used to cross-validate risk categories.

Results: Among 3133 patients, 309 (10%) experienced UHR. The best-performing model had a balanced accuracy of 0.56, with a sensitivity of 58% and a specificity of 54%. Predictors were polypharmacy, male sex, haemoglobin level, number of general practitioner contacts and multimorbidity. Excessive polypharmacy (>9 medications) was associated with a 55% increase in UHR odds. Three UHR risk groups were identified: low-risk (5.1%), medium-risk (8.8%) and high-risk (11.6%).

Conclusions: UHR are common in older adults, with excessive polypharmacy emerging as a key predictor. The pragmatic model described here provides a valuable tool to stratify older adults into distinct risk groups, identifying a high-risk group that may benefit from targeted interventions.

The management of oncological treatment has evolved substantially with the increasing use of oral antineoplastic agents, which are self-administered by patients or caregivers at home, and require careful monitoring and support. The aim of this study was to evaluate the impact of pharmaceutical consultations on oncology patients undergoing therapy with oral antineoplastic agents. A systematic literature review was conducted using the PubMed, Scopus and Web of Science databases with the last search on 5 June 2025. Primary observational or experimental studies were sought for inclusion. Eligible studies assessed the outcomes of pharmaceutical consultations for oncology patients receiving oral antineoplastic therapy in a hospital setting, compared with a conventional medication dispensing model. The risk of bias in the included studies was evaluated using the Cochrane risk-of-bias tools, RoB-2 and ROBINS-I. The review was developed in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020 Statement, and the protocol for the systematic literature review was registered with PROSPERO under the reference CRD42024533367. From the 881 records initially identified, 16 studies were included. A backward reference search led to the inclusion of two additional publications, bringing the total to 18 studies in this systematic review. The main interventions performed by pharmacists during pharmaceutical consultations included patient education on their treatment, management of adverse reactions and drug interactions, and monitoring of adherence to therapy. The studies evaluated a total of 10 variables, demonstrating the benefits of pharmaceutical consultation in all of them. Significant benefits were observed in terms of progression-free survival and quality of life, both of which are crucial in cancer treatment. However, further research is required, particularly involving larger patient samples and studies spanning multiple institutions and countries. To facilitate a comprehensive and comparative evaluation of different pharmaceutical consultation models in oncology, it would be advantageous to standardise methods for assessing their impact.

Objectives: Caffeine citrate, a methylxanthine derivative, is commonly used in the management of apnoea of prematurity. In clinical settings, particularly in neonatal intensive care units, various dilutions of caffeine citrate in intravenous fluids are required to ensure precise and individualised dosing for extremely low birth weight infants. This study aimed to assess the stability of caffeine citrate solutions at concentrations of 1 mg/mL and 12.5 mg/mL in 0.9% w/v sodium chloride and 5% w/v glucose, stored at room temperature and under refrigeration up to 48 hours.

Methods: Caffeine citrate concentrations were measured using a high-performance liquid chromatography method with ultraviolet detection (HPLC-UV). Solutions were stored at room temperature (22°C) and at 8°C for up to 48 hours. Two solvents for caffeine citrate were studied: normal saline (0.9% w/v sodium chloride), and 5% w/v glucose. The calibration curves of the HPLC-UV method were linear over the range of 0.1-12.5 mg/mL for both types of intravenous fluid. The stability criterion was defined according to International Council for Harmonisation (ICH) M10 (±15% of nominal concentration), and compliance with the stricter United States Pharmacopeia (USP) criterion (±10%) was also assessed.

Results: All samples remained within the ICH M10 acceptance limits. Most results also complied with the USP±10% threshold; however, three values (12.5 mg/mL in 0.9% w/v sodium chloride at 24 hours refrigerated, and 1 mg/mL in 5% w/v glucose at 24 hours and 48 hours refrigerated) exceeded 110% (112.9%, 111.3%, and 111.4%, respectively).

Conclusions: Caffeine citrate diluted in 0.9% w/v sodium chloride or 5% w/v glucose is chemically stable at concentrations of 1 mg/mL and 12.5 mg/mL for up to 48 hours when stored at room temperature, meeting ICH and USP acceptance criteria in all cases. Caffeine citrate solutions did not meet the USP±10% criterion if stored at 8°C for 24 hours.

Introduction: Nefopam is a non-opioid analgesic used for postoperative pain control. For intravenous home use, a portable elastomeric device is often preferred for administration. The nefopam in the device must be stable at 32°C because this device is positioned close to the patient.

Objectives: This study aimed to evaluate the physicochemical stability of nefopam solutions at 0.2 and 3.33 mg/mL diluted in 0.9% NaCl in silicone portable elastomeric devices at 32°C in the dark.

Methods: Three portable elastomeric devices were prepared for each condition. Chemical stability was assessed by pH measurement and high-performance liquid chromatography (HPLC). The method was validated according to the International Conference on Harmonisation Q2(R1). Stability was tested after preparation and after 6 and 24 hours of storage. At each time of analysis, the pH values were measured, and three samples from each device were analysed via HPLC. The solution is chemically stable if it retains more than 90% of its initial concentration, with the appearance of any degradation products monitored, and if the pH variation is less than one unit. Physical stability was evaluated by visual and subvisual inspection using a particle counter following the European Pharmacopoeia guidelines.

Results: Nefopam solutions at both concentrations maintained more than 93% of their initial concentration after 6 and 24 hours at 32°C, with no pH variation exceeding one unit, demonstrating chemical stability. For both concentrations, visual inspection was compliant at each analysis time, and subvisual inspection was consistent at 24 hours. Physical stability was therefore demonstrated for both concentrations after 24 hours.

Conclusions: The physicochemical stability of nefopam solutions at 0.2 and 3.33 mg/mL was demonstrated for 24 hours at 32°C in portable elastomeric infusion devices. This attribute allows continuous administration at home, particularly in cases of difficulty with oral administration, or minimises the side effects of discontinuous administration.