OBJECTIVES:Business continuity plans (BCPs) are vital for hospital pharmacies (HPs) seeking to maintain essential operations during crises. Although generic BCPs exist, we found no guidelines for HP BCPs. We sought to use an expert consensus methodology to develop specific recommendations for BCP content for HPs. METHODS:An expert panel comprising hospital chief pharmacists, deputies or quality managers conducted a two-round Delphi study. Participants were recruited from civilian HPs in Switzerland and from two civilian and one military HP in each of Austria, Belgium, France, Germany and Italy. Recommendations were structured around the 'all-hazards' framework and practical examples were developed based on the literature and investigators' experiences in disaster simulation. A five-member multidisciplinary steering committee refined the recommendations before each round of voting. Experts rated recommendations on a scale from 1 to 9, and the RAND/UCLA method was used to determine consensus. In Round 2, recommendations without consensus in Round 1, newly proposed recommendations and recommendations with comments in Round 1 requiring rephrasing were submitted. RESULTS:Of 71 experts contacted, 24 participated, with 18 responding in Round 1 (75% response rate) and 15 responding in Round 2 (83% response rate). Most experts came from Switzerland (78%) and civilian hospitals (94%). Half were chief pharmacists and only 17% had no BCP available in their HP. In Round 1, 41 recommendations were submitted, of which 100% were validated. Eleven recommendations were submitted in Round 2, including one new proposal and 10 rephrased recommendations from Round 1. Experts had to select their preferred version. The new recommendation was validated and all the rephrased recommendations were preferred. The final list comprised 42 recommendations for developing BCPs for HPs. CONCLUSION:Our consensus-based BCP guidelines provide practical recommendations for civilian and military HPs and will help them develop BCPs for future crises and major business disruptions.

Hyperprolactinaemia is a common adverse effect of antipsychotic medication, primarily resulting from dopamine D2 receptor blockade. It is characterised by menstrual irregularities, gynaecomastia, galactorrhoea and, with prolonged exposure, an increased risk of osteoporosis and breast cancer. When switching towards a prolactin-sparing antipsychotic is not feasible, adjunctive use of aripiprazole - a dopamine D2 partial agonist - has emerged as a validated strategy to mitigate hyperprolactinaemia without compromising antipsychotic efficacy. However, alternative options are needed for patients who cannot tolerate aripiprazole. Here we report the use of brexpiprazole, a dopamine D2 partial agonist structurally related to aripiprazole, to counteract paliperidone-induced hyperprolactinaemia effectively in a patient who developed a cutaneous reaction to aripiprazole. During the follow-up period with adjunctive brexpiprazole in combination with paliperidone, neither a recurrence of psychotic symptoms nor a reappearance of the skin reaction previously experienced with aripiprazole was observed.

BACKGROUND:This review re-evaluates therapeutic drug monitoring (TDM) by comparing the current analytical and subsequent clinical interpretation capabilities of hospital or community medical laboratories with the emerging potential of point-of-care (POC) devices, which could become increasingly utilized in hospital wards, day-hospital units, and outpatient clinic settings. METHODS:A narrative review was conducted to identify publications that best illustrate the current trends in the development of POC TDM. RESULTS:The latest scientific and technical literature indicates that POC devices for determining drug concentrations in clinical samples are approaching the market. Several technologies are now available to develop portable sensors capable of rapidly returning concentration measurements. Interfacing these methods with artificial intelligence-based pattern recognition may enhance the identification and quantification of drugs. However, once the drug concentration is accurately measured using a portable device, dosage adjustments require consideration of the drug's pharmacokinetics and the patient's characteristics. This is accounted for in the mathematical approaches underlying model-informed precision dosing, which consider inter- and intra-individual variability and provide recommendations for treatment adjustments. These complexities necessitate the use of digital technologies, including graphical interfaces, machine learning approaches, and secure connectivity, to enhance the application of TDM in clinical practice. CONCLUSIONS:Promising emerging technologies have considerable potential to expand TDM to cover a wide range of drugs, making precision medicine accessible to many patients.

Introduction In South Sudan's ongoing humanitarian crisis, Pharmacists Without Borders Switzerland (PSF) implemented an e-learning project at the rural St Vincent Health Care Centre (CSSV) to strengthen pharmaceutical management capabilities. Methods Five e-learning modules from the Pharm-Ed project were deployed, covering pharmaceutical management and targeting CSSV staff members. A PSF pharmacist delivered these on a USB stick on an on-site mission in July 2022, along with an initial field assessment using a 23-item evaluation grid. A follow-up assessment in April 2024 also included a workshop on substandard and falsified medical products, with pre- and post-tests to measure learning outcomes. Results Only two staff members reported completing the e-learning course and one completed the corresponding examinations. Field assessments showed limited improvements in pharmaceutical management practices, with only 3 out of 23 items progressing substantially. The workshop, attended by all the CSSV staff, resulted in slight increase in knowledge (mean score rising from 3.0±1.6 to 3.7±1.8 out of 10 points). Discussion While e-learning shows promise and a growing interest in the literature, our experience highlighted numerous barriers to this method in humanitarian settings (technological issues, language barriers, or unstable geopolitical context). A blended-learning strategy combining online and face-to-face training may be more effective. More structured follow-up and additional field visits could enhance Pharm-Ed modules buy-in, while incorporating practical activities and local language translation could improve workshops. Conclusion Without a permanent PSF on-site presence, innovative approaches are needed to transfer skills to the CSSV. Staff expressed interest in further training, indicating potential for future e-learning initiatives in crisis and resource-limited settings, though its effectiveness requires careful adaptation to local contexts and ongoing support.

Incidents involving ionizing radiation pose a risk of immediate and long-term clinical consequences for both victims and responders in the event of secondary contamination. Rapid identification of the problem and a coordinated response are crucial. This article summarizes the key challenges related to the emergency management of a single patient or multiple victims, addressing the importance of recognizing such a case, radioprotection measures, decontamination, and available treatments.

Incidents involving ionizing radiation pose a risk of immediate and long-term clinical consequences for both victims and responders in the event of secondary contamination. Rapid identification of the problem and a coordinated response are crucial. This article summarizes the key challenges related to the emergency management of a single patient or multiple victims, addressing the importance of recognizing such a case, radioprotection measures, decontamination, and available treatments.

Most traditional cytotoxic drugs are characterized by steep dose–response relationships and narrow therapeutic windows [...]

Therapeutic drug monitoring (TDM) of conventional cytotoxic chemotherapies is strongly supported yet poorly implemented in daily practice in hospitals. Analytical methods for the quantification of cytotoxic drugs are instead widely presented in the scientific literature, while the use of these therapeutics is expected to keep going for longer. There are two main issues hindering the implementation of TDM: turnaround time, which is incompatible with the dosage profiles of these drugs, and exposure surrogate marker, namely total area under the curve (AUC). Therefore, this perspective article aims to define the adjustment needed from current to efficient TDM practice for cytotoxics, namely point-of-care (POC) TDM. For real-time dose adjustment, which is required for chemotherapies, such POC TDM is only achievable with analytical methods that match the sensitivity and selectivity of current methods, such as chromatography, as well as model-informed precision dosing platforms to assist the oncologist with dose fine-tuning based on quantification results and targeted intervals.

Background The COVID-19 pandemic strained healthcare systems immensely as of 2020. Switzerland’s hospital pharmacies’ responses during the first wave were surveyed with a view to improving the quality of pharmaceutical management in future health crises. Methods An online survey was sent to the heads of all of Switzerland’s hospital pharmacies. The questionnaire was organised into eleven sections of questions covering many topics regarding the management of COVID-19’s first wave. Data collection occurred from May to June 2020. Results Analyses were performed using the 43 questionnaires (66%), with at least one answer per questionnaire, out of 65 distributed. Seventeen of 41 pharmacies responding (41%) had existing standard operating procedures or pandemic plans and 95% of these (39/41) set up crisis management steering committees. Twenty-nine of 43 pharmacies responding (67%) created new activities to respond to the pandemic’s specific needs. Twenty-six of 39 pharmacies responding (67%) created new drug lists for: COVID-19-specific treatments (85%; 22/26), sedatives (81%; 21/26), anaesthetics (77%; 20/26) and antibiotics (73%; 19/26). Drug availability in designated COVID-19 wards was managed by increasing existing stocks (54%; 22/41 pharmacies) and creating extra storage space (51%; 21/41). Two drugs generated the greatest concern about shortages: propofol (49%; 19/39 pharmacies) and midazolam (44%; 17/39). Remdesivir stocks ran out in 26% of pharmacies (10/39). Twelve of 43 pharmacies (28%) drafted specific new documents to respond to medical needs regarding drug administration, 12 (28%) did so for drug preparation and 10 (23%) did so for treatment choices. Conclusions Switzerland’s hospital pharmacies encountered many challenges related to the COVID-19 crisis and had to find solutions quickly, effectively and safely. The survey highlighted the key role that hospital pharmacies played in many aspects of the pandemic by providing logistical and clinical support to medical and nursing care teams. The lessons and experiences outlined could be used to improve the quality of hospital pharmacies’ readiness for similar future events.

Imatinib is a targeted cancer therapy that has significantly improved the care of patients with chronic myeloid leukemia (CML) and gastrointestinal stromal tumor (GIST). However, it has been shown that the recommended dosages of imatinib are associated with trough plasma concentration (Cmin) lower than the target value in many patients. The aims of this study were to design a novel model-based dosing approach for imatinib and to compare the performance of this method with that of other dosing methods. Three target interval dosing (TID) methods were developed based on a previously published PK model to optimize the achievement of a target Cmin interval or minimize underexposure. We compared the performance of those methods to that of traditional model-based target concentration dosing (TCD) as well as fixed-dose regimen using simulated patients (n = 800) as well as real patients' data (n = 85). Both TID and TCD model-based approaches were effective with about 65% of Cmin achieving the target imatinib Cmin interval of 1000-2000 ng/mL in 800 simulated patients and more than 75% using real data. The TID approach could also minimize underexposure. The standard 400 mg/24 h dosage of imatinib was associated with only 29% and 16.5% of target attainment in simulated and real conditions, respectively. Some other fixed-dose regimens performed better but could not minimize over- or underexposure. Model-based, goal-oriented methods can improve initial dosing of imatinib. Combined with subsequent TDM, these approaches are a rational basis for precision dosing of imatinib and other drugs with exposure-response relationships in oncology.

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Abstract Purpose Assess whether full-scale simulation exercises improved hospital pharmacies’ disaster preparedness. Methods Swiss hospital pharmacies performed successive full-scale simulation exercises at least four months apart. An interprofessional team created two scenarios, each representing credible regional-scale disasters involving approximately fifty casualties (a major road accident and a terrorist attack). Four exercise assessors used appraisal forms to evaluate participants’ actions and responses during the simulation (rating them using five-point Likert scales). Results Four hospital pharmacies performed two full-scale simulation exercises each. Differences between exercises one and two were observed. On average, the four hospitals accomplished 69% ± 6% of the actions expected of them during exercise one. The mean rate of expected actions accomplished increased to 84% ± 7% (p < 0.005) during exercise two. Moreover, the average quality of actions improved from 3.0/5 to 3.6/5 (p = 0.01), and the time required to gather a crisis management team drastically decreased between simulations (from 23 to 5 min). The main challenges were communication (reformulation) and crisis management. Simulation exercise number one resulted in three hospital pharmacies creating disaster action plans and the fourth improving its already existing plan. Conclusion This study highlighted the value of carrying out full-scale disaster simulations for hospital pharmacies as they improved overall institutional preparedness and increased staff awareness. The number of expected actions accomplished increased significantly. In the future, large-scale studies and concept dissemination are warranted.

OBJECTIVESImipenem is a broad-spectrum antibacterial agent used in critically ill neonates after failure of first-line treatments. Few studies have described imipenem disposition in this population. The objectives of our study were: (i) to characterize imipenem population pharmacokinetics (PK) in a cohort of neonates; and (ii) to conduct model-based simulations to evaluate the performance of six different dosing regimens aiming at optimizing PK target attainment.METHODSA total of 173 plasma samples from 82 neonates were collected over 15 years at the Lausanne University Hospital, Switzerland. The majority of study subjects were preterm neonates with a median gestational age (GA) of 27 weeks (range: 24-41), a postnatal age (PNA) of 21 days (2-153) and a body weight (BW) of 1.16 kg (0.5-4.1). PK data were analysed using non-linear mixed-effect modelling (NONMEM).RESULTSA one-compartment model best characterized imipenem disposition. Population PK parameters estimates of CL and volume of distribution were 0.21 L/h and 0.73 L, with an interpatient variability (CV%) of 20.1% on CL in a representative neonate (GA 27 weeks, PNA 21 days, BW 1.16 kg, serum creatinine, SCr 46.6 μmol/L). GA and PNA exhibited the greatest impact on PK parameters, followed by SCr. These covariates explained 36% and 15% of interindividual variability in CL, respectively.Simulated regimens using a dose of 20-25 mg/kg every 6-12 h according to postnatal age led to the highest PTA (T>MIC over 100% of time).CONCLUSIONSDosing adjustment according to BW, GA and PNA optimizes imipenem exposure in neonates.

ABSTRACTObjective:This study was focused on reviewing the emergency and disaster preparedness of European hospital pharmacists.Methods:An online survey based on International Pharmaceutical Federation (FIP) guidelines for natural disasters was sent to European hospital pharmacies, with the support of the European Association of Hospital Pharmacists. Additional questions were added about the characteristics of respondents, as well as preparedness and experience of manmade disasters. Descriptive statistics were used to analyze the results.Results:Hospital pharmacists in France (20%) and Spain (19%) returned most of the 306 questionnaires completed in 27 countries. Half of the respondents had analyzed their regional disaster risk, but 65% had never practiced emergency drills. Fifteen percent of respondents had experienced at least 1 major emergency or disaster event in the last 5 years. Fifty-six percent of those respondents who experienced a disaster subsequently created and promoted internal standard operating procedures (SOPs) for future emergencies, versus 23% for those who had not experienced disasters. Among pharmacists having experienced disasters, 40% organized a post-disaster debriefing to improve their future response.Conclusions:Results highlighted that most European hospital pharmacists were not fully compliant with FIP guidelines. However, respondents who had experienced disasters were more likely to create and promote SOPs for future disasters. Further worldwide analysis and benchmarking are necessary, and FIP guidelines should be more strongly promoted.

This study aimed to determine whether published pharmacokinetic (PK) models can adequately predict the PK profile of imatinib in a new indication, such as coronavirus disease 2019 (COVID-19). Total (bound + unbound) and unbound imatinib plasma concentrations obtained from 134 patients with COVID-19 participating in the CounterCovid study and from an historical dataset of 20 patients with gastrointestinal stromal tumor (GIST) and 85 patients with chronic myeloid leukemia (CML) were compared. Total imatinib area under the concentration time curve (AUC), maximum concentration (Cmax ) and trough concentration (Ctrough ) were 2.32-fold (95% confidence interval [CI] 1.34-3.29), 2.31-fold (95% CI 1.33-3.29), and 2.32-fold (95% CI 1.11-3.53) lower, respectively, for patients with CML/GIST compared with patients with COVID-19, whereas unbound concentrations were comparable among groups. Inclusion of alpha1-acid glycoprotein (AAG) concentrations measured in patients with COVID-19 into a previously published model developed to predict free imatinib concentrations in patients with GIST using total imatinib and plasma AAG concentration measurements (AAG-PK-Model) gave an estimated mean (SD) prediction error (PE) of -20% (31%) for total and -7.0% (56%) for unbound concentrations. Further covariate modeling with this combined dataset showed that in addition to AAG; age, bodyweight, albumin, CRP, and intensive care unit admission were predictive of total imatinib oral clearance. In conclusion, high total and unaltered unbound concentrations of imatinib in COVID-19 compared to CML/GIST were a result of variability in acute phase proteins. This is a textbook example of how failure to take into account differences in plasma protein binding and the unbound fraction when interpreting PK of highly protein bound drugs, such as imatinib, could lead to selection of a dose with suboptimal efficacy in patients with COVID-19.

Objectives To ensure patient safety and the preparedness of medication processes during hospital relocations and evacuations by using Failure Modes, Effects, and Criticality Analysis (FMECA). Methods The relocation of six regional hospitals to a single building, resulting in 400 beds being moved, could be compared with an emergency evacuation. An FMECA was performed on the hospital group's internal medicine and intensive care units (IMU and ICU), examining how medication processes would be affected by a hospital relocation or evacuation. Results We identified 59 hospital relocation and 68 evacuation failure modes. Failure modes were ranked based on their criticality index (CI; range 1-810). The higher the CI, the greater the patient-related risk. Average initial IMU and ICU hospital relocation CI scores were 160 (range 105-294) and 201 (range 125-343), respectively, subsequently reduced to 32 (-80%) and 49 (-76%) after mitigation measures. Average initial IMU and ICU evacuation CI scores were 319 (range 245-504) and 592 (range 441-810), respectively, subsequently reduced to 194 (-39%) and 282 (-52%). Most mitigation measures (17/22), such as for example checklists, could be implemented in both situations. Due to their unpredictable nature, five measures were specific to evacuation situations. Conclusions This study highlights the value of using an FMECA on medication processes to anticipate potential negative impacts on patient safety during hospital relocations or evacuations. Preparation for a hospital relocation can provide useful knowledge and an opportunity to test mitigation measures that might prove useful in evacuations.

Transition between hospital and ambulatory care is a delicate step involving several healthcare professionals and presenting a considerable risk of drug-related problems. To investigate pharmaceutical interventions made on hospital discharge prescriptions by community pharmacists. This observational, prospective study took place in 14 community pharmacies around a Swiss acute care hospital. We recruited patients with discharge prescriptions (minimum three drugs) from the internal medicine ward of the hospital. The main outcome measures were: number and type of pharmaceutical interventions made by community pharmacists, time spent on discharge prescriptions, number of medication changes during the transition of care. The study included 64 patients discharged from the hospital. Community pharmacists made a total of 439 interventions; a mean of 6.9 ± 3.5 (range 1–16) interventions per patient. All of the discharge prescriptions required pharmaceutical intervention, and 61 (95%) necessitated a telephone call to the patients’ hospital physician for clarifications. The most frequent interventions were: confirming voluntary omission of a drug (31.7%), treatment substitution (20.5%), dose adjustment (16.9%), and substitution for reimbursement issues (8.8%). Roughly half (52%) of all discharge prescriptions required 10–20 min for pharmaceutical validation. The mean number of medication changes per patient was 16.4: 9.6 changes between hospital admission and discharge, 2.6 between hospital discharge and community pharmacy, and 4.2 between community pharmacy and a general practitioner’s appointment. Hospital discharge prescriptions are complex and present a significant risk of medication errors. Community pharmacists play a key role in preventing and identifying drug-related problems.

Background The strengthening or substitution of intravenous cytotoxic chemotherapy cycles by oral targeted anticancer therapies, such as protein kinase inhibitors (PKIs), has provided impressive clinical benefits and autonomy as well as a better quality of life for patients with cancer. Despite these advances, adverse event management at home and medication adherence remain challenging. In addition, PKI plasma concentrations vary significantly among patients with cancer receiving the same dosage, which could explain part of the observed variability in the therapeutic response. Objective The aim of this optimizing oral targeted anticancer therapies (OpTAT) study is to optimize and individualize targeted anticancer treatments to improve patient care and self-monitoring through an interprofessional medication adherence program (IMAP) combined with measurement PKI plasma concentrations. Methods The OpTAT study has two parts: (1) a 1:1 randomized medication adherence program, in which the intervention consists of regular motivational interviewing sessions between the patient and the pharmacist, along with the delivery of PKIs in electronic monitors, and (2) a systematic collection of blood samples and clinical and biological data for combined pharmacokinetic and pharmacodynamic analysis. On the basis of the electronic monitor data, medication adherence will be compared between groups following the three operational definitions: implementation of treatment during the persistent period, persistence with treatment and longitudinal adherence. The implementation will be described using generalized estimating equation models. The persistence of PKI use will be represented using a Kaplan-Meier survival curve. Longitudinal adherence is defined as the product of persistence and implementation. PKI pharmacokinetics will be studied using a population approach. The relationship between drug exposure and efficacy outcomes will be explored using Cox regression analysis of progression-free survival. The relationship between drug exposure and toxicity will be analyzed using a pharmacokinetic-pharmacodynamic model and by logistic regression analysis. Receiver operating characteristic analyses will be applied to evaluate the best exposure threshold associated with clinical benefits. Results The first patient was included in May 2015. As of June 2021, 262 patients had participated in at least one part of the study: 250 patients gave at least one blood sample, and 130 participated in the adherence study. Data collection is in process, and the final data analysis is planned to be performed in 2022. Conclusions The OpTAT study will inform us about the effectiveness of the IMAP program in patients with solid cancers treated with PKIs. It will also shed light on PKI pharmacokinetic and pharmacodynamic properties, with the aim of learning how to adapt the PKI dosage at the individual patient level to increase PKI clinical suitability. The IMAP program will enable interprofessional teams to learn about patients’ needs and to consider their concerns about their PKI self-management, considering the patient as an active partner. Trial Registration ClinicalTrials.gov NCT04484064; https://clinicaltrials.gov/ct2/show/NCT04484064. International Registered Report Identifier (IRRID) DERR1-10.2196/30090