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

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.

Objectives: Inappropriate prescriptions are known to cause medication-related problems, but little is known about the prevalence of this issue in paediatric patients. This systematic review provides an overview of the prevalence of potentially inappropriate prescriptions identified through tools developed for the paediatric population and delineates the strengths and limitations of the identification tools.

Methods: Literature from PubMed, CINAHL, Cochrane database and Google Scholar was searched with a combination of medical subject headings (MeSH) and free-text terms related to inappropriate prescriptions, paediatrics and potentially inappropriate prescription tools. Studies reported in English and published from inception of the databases until May 2023 were selected based on fulfilment of eligibility criteria. All eligible articles were assessed for methodological quality and examined using thematic analysis.

Results: Twelve studies met the inclusion criteria. The majority of the studies were of high quality. Four themes emerged-namely, evaluation tools and calculation methods of inappropriate prescriptions, prevalence of potentially inappropriate medications (PIMs) and potential prescribing omissions (PPOs), and predictors of PIM and PPO in children. Among the nine tools identified, the original and modified version of the POPI tool was most commonly used. The prevalence of PIM and PPO ranged from 0.04% to 69% and from 1.5% to 55.9%, respectively. Age was the most common predictor reported, whereby PIMs and PPOs were more likely in children aged 2-6 and 6-12 years, respectively.

Conclusions: Potentially inappropriate prescriptions in paediatric patients is highly prevalent, despite the wide variation in the reported prevalence range and limited implementation of the available tools in practice. Future efforts need to be focused on the development and implementation of age-, disease- or country-specific tools to effectively evaluate and further determine the economic impact of PIMs in children.

Objectives: To assess the physicochemical stability of the combination of a propofol emulsion with an alpha-2 (α2) adrenergic receptor agonist (α2A; clonidine or dexmedetomidine) under conditions mimicking routine practice in an intensive care unit or in multimodal analgesia procedures.

Methods: We developed and validated three stability-indicating methods based on high-performance liquid chromatography with ultraviolet (HPLC-UV) detection. Eight different conditions per combination were evaluated in triplicate, with variations in the simulated, bodyweight-adjusted dose level and the drugs' flow rate. The drugs were mixed in clinically relevant concentrations and proportions and then stored unprotected from light, in clear glass vials at room temperature for 96 hours. At each sampling point, we assessed the chemical stability (the HPLC-UV drug level, pH, and osmolality) and physical compatibility (visual aspect, zeta potential (ZP), mean droplet diameter (MDD, Z-average) and polydispersity index (PDI)). We validated our stability findings in positive and negative control experiments.

Results: Over the 96-hour test, the concentrations of propofol, clonidine and dexmedetomidine did not fall below 90% of the initial value, and the pH and osmolality were stable. The visual aspect of the mixed propofol emulsions did not change. The MDD remained below 500 nm (range 165-195 nm). The PDI was always below 0.4; 78.7% of the measurements were below 0.1 and 21.3% were between 0.1 and 0.4. The ZP measurements (-31.3 to -42.9 mV) suggested that the emulsion was stable. The MDD and PDI increased slightly at 96 hours under some conditions, which might indicate early destabilisation of the emulsion. Given that the MDD remained below 500 nm, these emulsions are compatible with intravenous administration.

Conclusions: Our results demonstrate the chemical and physical compatibility of propofol-α2 agonist mixtures at concentrations and in proportions representative of standard protocols when stored unprotected from light at room temperature for 96 hours.

Background and objectives: Hospital pharmacists collaborate in clinical trials by managing the reception, conservation, distribution, return and destruction of the investigational medical products (IMP). However, errors can happen during the simultaneous management of multiple trials because each clinical trial stipulates its own method for managing the drug under study. In order to promote optimal management by hospital pharmacists, we developed a method for calculating a risk of error index for each experimental protocol, and wrote standard procedures for managing trials assigned low, moderate and high risk levels, to provide hospital pharmacists with a systematic tool for reducing human error in the management of IMPs for multiple clinical trials.

Methods: Calculation of this risk of error index (ρ) entails four factors: the pharmacological risk of error (φ) inherent in the pharmacological characteristics and route of administration of the IMP (carcinogenic, mutagenic, cytotoxic nature of the drug, parental or non-parenteral administration), the technological risk of error (α) involved should drug compounding be required, the risk of error related to the number of patients enrolled (n_p) and the risk of error intrinsic to the protocol (π) when it involves placebos, randomisation or other factors. We developed the formula [Formula: see text] to define trials as low (ρ<50), moderate (51<ρ<150) and high risk (ρ>151) for hospital pharmacist error.

Results: Calculations of this formula for 60 active trials indicated that seven (11.7%) of the protocols were low risk of hospital pharmacist error, 43 (71.7%) were moderate risk and 10 (16.6%) were high risk. For each of these categories (low, moderate and high risk) we have outlined standard procedures in order to minimise the occurrence of any errors.

Conclusions: Following validation of our formula and standard procedures by the ISMETT Research Institute, we are promoting the use of the tool in other clinical centres as we believe it can help hospital pharmacists minimise the risk of error in managing experimental drugs for clinical trials.

Objective: To determine the pharmaceutical interventions in patients eligible for phase I cancer clinical trials, focusing specifically on exclusion criteria related to medication or relevant interactions.

Method: Descriptive, observational study conducted at a comprehensive cancer centre. Patients undergoing screening for phase I clinical trials (March 2019-December 2022) were included. The pharmacist reviewed concomitant medication and provided a recommendation.

Results: The concomitant medication of 512 patients eligible to participate in 84 phase I clinical trials was analysed. In 230 (44.9%) patients, the clinical trial treatment included oral medication. The median number of concomitant medications was 5 (IQR 3-8) per patient.A total of 280 pharmaceutical interventions were performed in 140 (27.3%) patients: 240 (85.7%) were due to interactions in 124 (24.2%) patients, and 40 (14.3%) were due to exclusion criteria in 34 (6.6%) patients. Interactions and exclusion criteria were detected in 18 (3.5%) patients. The main groups of drugs involved were 68 (24.3%) antacids and antiulcer drugs, 28 (10.0%) antidepressants and 26 (9.3%) opioids. Acceptance analysis of the recommendation was applicable in 215 cases; in 208 (96.7%), the pharmaceutical intervention was accepted.Differences were identified for exclusion criteria (7 vs 27) and interactions (37 vs 87) between parenteral and oral clinical trial medication (p<0.001).

Conclusion: The pharmacist's review of concomitant medication during the screening period in phase I clinical trials enables the detection of prohibited medication or relevant interactions, potentially avoiding screening failures and increasing the efficacy and safety of treatments.

Introduction: The COVID-19 pandemic has led to unforeseen and novel manifestations, as illustrated by the management of drug shortages through the development of hospital production of sterile pharmaceutical preparations (P2S). Visual inspection of P2S is a release control whose methods are described in monographs of the European Pharmacopoeia (2.9.20) and the United States Pharmacopeia (1790). However, these non-automated visual methods require training and proficiency testing of personnel. The main objective of this work was to compare the reliability and speed of analysis of two visual methods and an automated method for detecting visible particles by image analysis in P2S. Furthermore, these methods were used to evaluate sources of particulate contamination during pre-production processes (washing, disinfection, depyrogenation) and production (filling, capping).

Materials and methods: Three pharmacy technicians examined 41 clear glass vials of type I, 10 and/or 50 mL through manual visual inspection (MVI), semi-automated (SAVI), and automated (AVI) inspection. The vials were distributed as follows: (i) 16 vials of water for injection containing either glass particles (224 µm or 600 µm), stopper fragments, or textile fibres; (ii) five sterile injectable specialties; (iii) 20 vials of water for injection prepared under different pre-production conditions.

Results and discussion: MVI and SAVI detected 100% of visible particles compared with 28% for AVI, which showed a deficiency in detecting textile fibres. All three methods correctly analysed P2S that did not contain visible particles. The three methods detected particles in vials maintained under International Organization for Standardization (ISO) 9 pre-production conditions. However, detections by (i) MVI and SAVI, and by (ii) AVI of particles contained in vials maintained under ISO 8 pre-production conditions were deemed satisfactory and unsatisfactory, respectively.

Conclusion: The importance of visual inspection of P2S requires rapid, sensitive, and reliable detection methods. In this context, MVI and SAVI have proven to be more effective than AVI for a more competitive financial, training, and implementation investment.

Introduction: Acute respiratory distress syndrome (ARDS) is a life-threatening, diffuse inflammatory pulmonary condition characterised by the Berlin criteria. Incidence of ARDS is estimated at 2.5-19% globally with high mortality and morbidity. Interest has been increasing in the use of inhaled sedatives because of a more rapid awakening and fewer adverse effects compared with intravenous propofol. The primary aim of this systematic review protocol is to investigate the length of critical care stay between ARDS patients who have been mechanically ventilated with inhaled anaesthetic sedatives (ie, sevoflurane and isoflurane) compared with those patients who are prescribed conventional sedatives (ie, propofol).

Methods and analysis: Cochrane Central Register of Controlled Trials, Ovid (Embase, MEDLINE), PubMed, EBSCO (CINAHL Plus), Google Scholar will be searched and stratified by the reviewers. The literature search will be limited to English articles. Published full text peer-reviewed articles will be included.The International Prospective Register of Systematic Reviews (PROSPERO) Registration number is: CRD42023390988.

Ethics and dissemination: Ethics approval is not required for this systematic review. The results will be presented at local/regional meetings and dissemination will occur through peer-reviewed publication.

Objectives: Vancomycin, a glycopeptide antibiotic has antibacterial activity against Gram-positive bacteria and is frequently used in the intensive care unit (ICU). Inappropriate therapeutic drug monitoring (TDM) of vancomycin is a common problem encountered in hospital daily practice. The aim of this study was to evaluate the appropriateness of vancomycin trough-guided TDM in patients treated in the ICU using a clinical pharmacy approach.

Methods: The study was conducted retrospectively in patients over 18 years old who had at least one vancomycin trough level and who had received intravenous (IV) vancomycin for ≥3 days between 1 November 2020 and 1 April 2022. The study included 137 patients. Patient demographics and relevant vancomycin TDM data were collected from medical records. The appropriateness of TDM was evaluated according to the criteria established based on the monitoring recommendations specified in consensus guidelines for therapeutic drug monitoring of vancomycin published by the American Society of Health-System Pharmacists (ASHP) in 2009 and 2020.

Results: Of a total of 238 vancomycin trough levels measured in patients, 32.4% were collected at an inappropriate time. When patients were evaluated in terms of TDM appropriateness according to vancomycin level ranges (<10 µg/mL, 10-20 µg/mL and >20 µg/mL), we found the appropriate TDM was significantly higher in the therapeutic range (10-20 µg/mL) (p <0.001). Of the total 238 vancomycin trough concentrations taken from patients, 77 (32.4%) were measured at an inappropriate time. This caused dose withholding, wrong adjustments and therapy failure. The total TDM appropriateness of vancomycin was significantly higher in the therapeutic range defined as 10-20 µg/mL when evaluated based on 'TDM appropriateness criteria' (p <0.001).

Conclusion: Our study shows that appropriate vancomycin TDM increases the likelihood of achieving target trough concentrations. Involvement of clinical pharmacists in TDM management may prevent the development of adverse reactions by ensuring appropriate sampling time and appropriate interpretation of vancomycin levels.