Optimizing pharmaceutical management of clinical trials.

OBJECTIVES: The clinical trials pharmacists have an essential role in managing the pharmaceutical part of interventional studies. The primary objective of this article was to provide a template for improving trials management for the growing number of studies without increasing personnel resources. MATERIAL AND METHODS: A retrospective study was conducted between 2016 and 2020 at the service of pharmacy at Lausanne University Hospital in Switzerland. RESULTS: The number of clinical trials (in progress) managed at the pharmacy increased from 77 to 115 (+49%) between 2016 and 2020. The majority of these studies were in oncology and were sponsored by industry. Therefore, different changes in routine tasks were decided during the 5 years term to meet the above challenge. These modifications allowed to improve pharmaceutical and administrative management of clinical trials, without increasing personnel resources. The management template was accepted by the sponsors, and no issues were mentioned by national and international audit authorities. CONCLUSION: Changes could be made in the routine practice of the clinical trials pharmacists to improve the management of studies, while the number of trials is increasing every year.

Management of Atrial Fibrillation Following Cardiac Surgery: Observational Study and Development of a Standardized Protocol.

BACKGROUND: Postoperative atrial fibrillation (POAF) is the most common complication occurring after cardiac surgery. Guidelines for the management of this complication are scarce, often resulting in differences in treatment strategy use among patients. OBJECTIVE: To evaluate the management of POAF in a cardiac surgery department, characterize the extent of its variability, and develop a standardized protocol. METHODS: This was an observational retrospective study with data from patients who underwent cardiac surgeries with subsequent POAF between January 1, 2017, and June 1, 2018. We assessed the difference in the proportions of patients whose first POAF episodes were treated with a rate control (RaC) strategy, a rhythm control (RhC) strategy, and both among different hospital units. We also assessed the mean duration of POAF episodes, POAF recurrences, and the management of anticoagulation. RESULTS: Data from 97 patients were included in this study. The POAF management strategy differed significantly among the 3 types of hospital units (P = 0.001). Considering all POAF episodes (including all recurrences), 83 of the 97 patients (85.6%) received amiodarone as part of the RhC strategy. Anticoagulation was used in 58 (59.8%) patients and was suboptimal according to the study criteria in 29.5% of the patients included. Based on these results, a hospital working group developed a standardized protocol for POAF management. CONCLUSIONS AND RELEVANCE: POAF management was heterogeneous at our institution. This article highlights the need for clear practice guidelines based on large prospective studies to provide care according to best practices.

Inhalation technique practical skills and knowledge among physicians and nurses in two pediatric emergency settings.

Introduction: Correct technique with a pressurized metered-dose inhaler (pMDI) equipped with a valved holding chamber (VHC) or spacer provides an important advantage for adequate control of asthma and virus-induced wheezing in young children. The aim of this study was to assess the ability and knowledge of physicians and nurses to use a pMDI with a masked VHC in two pediatric emergency units.Methods: Study design: Two-center observational study. Inhaler use technique was assessed in 50 physicians and 50 nurses using a child mannequin and a validated videotaped nine-step scoring method. The participants' knowledge was evaluated by a questionnaire.Results: The inhalation technique was perfectly mastered by 49% of the study participants and almost perfectly mastered by another 34% (mean score 8.3 ± 0.7; range 5-9). Nurses were more likely than doctors to demonstrate the technique perfectly (66% vs. 32%, p < 0.05). The two most common errors were forgetting to shake the pMDI between two consecutive puffs (38% of the participants) and putting the patient in an incorrect position (11%). About half of the participants reported that they checked each patient's inhalation technique at every opportunity and knew how to clean the VHC. A large majority did not employ a reliable method to determine the amount of medication remaining in pMDIs without a counter.Conclusion: Healthcare professionals' practical skills and knowledge on inhalation therapy were not completely mastered and could be improved with a mandatory training program.

Effects of the Interactive Web-Based Video "Mon Coeur, Mon BASIC" on Drug Adherence of Patients With Myocardial Infarction: Randomized Controlled Trial.

BACKGROUND: Secondary prevention strategies after acute coronary syndrome (ACS) presentation with the use of drug combinations are essential to reduce the recurrence of cardiovascular events. However, lack of drug adherence is known to be common in this population and to be related to treatment failure. To improve drug adherence, we developed the "Mon Coeur, Mon BASIC" video. This online video has been specifically designed to inform patients about their disease and their current medications. Interactivity has been used to increase patient attention, and the video can also be viewed on smartphones and tablets. OBJECTIVE: The objective of this study was to assess the long-term impact of an informative web-based video on drug adherence in patients admitted for an ACS. METHODS: This randomized study was conducted with consecutive patients admitted to University Hospital of Lausanne for ACS. We randomized patients to an intervention group, which had access to the web-based video and a short interview with the pharmacist, and a control group receiving usual care. The primary outcome was the difference in drug adherence, assessed with the Adherence to Refills and Medication Scale (ARMS; 9 multiple-choice questions, scores ranging from 12 for perfect adherence to 48 for lack of adherence), between groups at 1, 3, and 6 months. We assessed the difference in ARMS score between both groups with the Wilcoxon rank sum test. Secondary outcomes were differences in knowledge, readmissions, and emergency room visits between groups and patients' satisfaction with the video. RESULTS: Sixty patients were included at baseline. The median age of the participants was 59 years (IQR 49-69), and 85% (51/60) were male. At 1 month, 51 patients participated in the follow-up, 50 patients participated at 3 months, and 47 patients participated at 6 months. The mean ARMS scores at 1 and 6 months did not differ between the intervention and control groups (13.24 vs 13.15, 13.52 vs 13.68, respectively). At 3 months, this score was significantly lower in the intervention group than in the control group (12.54 vs 13.75; P=.03). We observed significant increases in knowledge from baseline to 1 and 3 months, but not to 6 months, in the intervention group. Readmissions and emergency room visits have been very rare, and the proportion was not different among groups. Patients in the intervention group were highly satisfied with the video. CONCLUSIONS: Despite a lower sample size than we expected to reach, we observed that the "Mon Coeur, Mon BASIC" web-based interactive video improved patients' knowledge and seemed to have an impact on drug adherence. These results are encouraging, and the video will be offered to all patients admitted to our hospital with ACS. TRIAL REGISTRATION: ClinicalTrials.gov NCT03949608; https://clinicaltrials.gov/ct2/show/NCT03949608.

[Fecal microbiota transplantation: from the evidence to the realty of the field]. / Transplantation de microbiote fécal : de l'évidence aux réalités du terrain.

In clinical practice, fecal microbiota transplantation (FMT) has been established as an unparalleled therapy to date for multiple recurrent Clostridioides difficile infections (CDI). The implementation of the FMT in practice requires a significant investment to meet legal, security and financial requirements. Research on the microbiota is booming and multiple investigations on FMT in indications other than CDI are ongoing.

En pratique clinique, la transplantation de microbiote fécal (TMF) s'est établie comme une thérapie sans équivalent à ce jour pour les infections à Clostridioides difficile (C. difficile) multirécidivantes. La mise en place de la TMF en pratique demande un investissement important pour répondre aux exigences légales, sécuritaires et financières. La recherche sur le microbiote est en plein essor et de multiples recherches sur la TMF dans d'autres indications que pour l'infection à C. difficile sont en cours.

Incident reports versus direct observation to identify medication errors and risk factors in hospitalised newborns.

Newborns are often exposed to medication errors in hospitals. Identification and understanding the causes and risk factors associated with medication errors will help to improve the effectiveness of medication. We sought to compare voluntary incident reports and direct observation in the identification of medication errors. We also identified corresponding risk factors in order to establish measures to prevent medication errors. Medication errors identified by a clinical pharmacist and those recorded in our incident reporting system by caregivers were analysed. Main outcomes were rates, type and severity of medication error, and other variables related to medication errors. Ultimately, 383 medication errors were identified by the clinical pharmacist, and two medication errors were declared by caregivers. Prescription errors accounted for 38.4%, preparation errors for 16.2%, and administration errors for 45.4%. The two variables significantly related to the occurrence of medication errors were gestational age < 32.0 weeks (p = 0.04) and the number of drugs prescribed (p < 0.01).Conclusion: Caregivers underreported the true rate of medication errors. Most medication errors were caused by inattention and could have been limited by simplifying the medication process. Risk of medication errors is increased in newborns < 32.0 weeks and increases with the number of drugs prescribed to each patient. What is Known: • Newborns in hospitals are particularly susceptible to medication errors. • Identification and understanding the reasons for medication errors should help us to establish preventive measures to reduce the occurrence of such errors. What is New: • Direct observation of the medication process, though time consuming, is essential to accurately assess the frequency of medication errors, which are underreported by caregivers. Most medication errors are caused by inattention and could be limited by simplifying the medication process. • The risk of medication errors was significantly increased in very preterm newborns (< 32 weeks) and when the number of prescription per patient increased.

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.

Population Pharmacokinetic Study of Amoxicillin-Treated Burn Patients Hospitalized at a Swiss Tertiary-Care Center.

The objective of this study was to investigate the population pharmacokinetics (PK) of amoxicillin in ICU burn patients and the optimal dosage regimens. This was a prospective study involving 21 consecutive burn patients receiving amoxicillin. PK data were analyzed using nonlinear mixed-effects modeling. Monte-Carlo simulations assessed the influence of various amoxicillin dosage regimens with identified covariates on the probability to achieve a target (PTA) value of time during which free amoxicillin concentrations in plasma exceeded the MIC (fT>MIC). A two-compartment model best described the data. Creatinine clearance (CLCR) and body weight (BW) influenced amoxicillin CL and central volume of distribution (V1), respectively. The median CLCR (Cockcroft-Gault formula) was high (128 ml/min), with 25% of patients having CLCRs of >150 ml/min. The CL, V1, and half-life (t1/2) values at steady state for a patient with a CLCR of 110 ml/min and BW of 70 kg were 13.6 liters/h, 9.7 liters, and 0.8 h, respectively. Simulations showed that a target fT>MIC of ≥50% was achieved (PTA > 90%) with standard amoxicillin dosage regimens (1 to 2 g every 6 to 8 h [q6-8h]) when the MIC was low (<1 mg/liter). However, increased dosages of up to 2 g/4 h were necessary in patients with augmented CLRs or higher MICs. Prolonging amoxicillin infusion from 30 min to 2 h had a favorable effect on target attainment. In conclusion, this population analysis shows an increased amoxicillin CL and substantial CL PK variability in burn patients compared to literature data with nonburn patients. Situations of augmented CLCR and/or high bacterial MIC target values may require dosage increases and longer infusion durations. (This study has been registered at ClinicalTrials.gov under identifier NCT01965340.).

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.

Does the introduction of an infliximab biosimilar always result in savings for hospitals? A descriptive study using real-world data.

BACKGROUND: Biosimilars are biologic drugs that have the potential to increase the efficiency of healthcare spending and curb drug-related cost increases. However, their introduction into hospital formularies through initiatives such as non-medical switching must be carefully orchestrated so as not to cause treatment discontinuation or result in increased health resource utilization, such as additional visits or laboratory tests, among others. This retrospective cohort study aims to assess the impact of the introduction of CT-P13 on the healthcare expenditures of patients who were treated with originator infliximab or CT-P13. METHODS: Gastroenterology, immunoallergology and rheumatology patients treated between September 2017 and December 2020 at a university hospital in Western Switzerland were included and divided into seven cohorts, based on their treatment pathway (i.e., use and discontinuation of CT-P13 and/or originator infliximab). Costs in Swiss francs were obtained from the hospital's cost accounting department and length of stay was extracted from inpatient records. Comparisons of costs and length of stay between cohorts were calculated by bootstrapping. RESULTS: Sixty immunoallergology, 84 rheumatology and 114 gastroenterology patients were included. Inpatient and outpatient costs averaged (sd) CHF 1,611 (1,020) per hospital day and CHF 4,991 (6,931) per infusion, respectively. The mean (sd) length of stay was 20 (28) days. Although immunoallergology and rheumatology patients had higher average costs than gastroenterology patients, differences in costs and length of stay were not formally explained by treatment pathway. Differences in health resource utilization were marginal. CONCLUSIONS: The introduction of CT-P13 and the disruption of patient treatment management were not associated with differences in average outpatient and inpatient costs and length of stay, in contrast to the results reported in the rest of the literature. Future research should focus on the cost-effectiveness of non-medical switching policies and the potential benefits for patients.

Development of a generic sample preparation method using dispersive liquid-liquid microextraction for the monitoring of leachable compounds in hospital pharmacy-prepared prefilled drug products.

Performant sample preparation is mandatory in any leachable study to clean and preconcentrate analytes within the sample to offer the best possible extraction recovery as well the best precision for any given substance. The aim consists in developing a sample preparation method for hospital pharmacy-prepared drug products such as long-term storage prefilled syringes, vials and IV bags for the screening of leachable compounds. The Quality Control Laboratory of the Pharmacy of the Lausanne University Hospital (Switzerland) has developed a time- and cost-effective, highly sensitive, robust, and fast method using liquid chromatography coupled with high-resolution mass spectrometry (LC-HRMS) for the analysis of 205 plastic additives. An innovative setup, based on postcolumn infusion (PCI) using 2% ammonium hydroxide in methanol was used to boost the signal intensity of the analytes in MS detection. A database for extractable and leachable trace assessment (DELTA) was built to assist in the screening process of 205 plastic packaging-related compounds. The development of the sample preparation was based on 33 plastic additive candidates in different hospital pharmacy compounding solutions, and their extraction recovery rates as well as their relative standard deviation were taken into consideration. In conclusion, the developed DLLME was assigned with ultrasound assistance and triple extraction, which brought about extraction recovery rates between 67% and 92%, a good RSD <10%, and a preconcentration factor of 50×. Therefore, DLLME could be considered suitable for the semiquantitative screening of leachable additives in simple hospital pharmacy-prepared prefilled drug products.

Development of a generic approach for monitoring leachable compounds in hospital pharmacy-prepared prefilled plastic packaging by ultrahigh-performance liquid chromatography coupled to high-resolution mass spectrometry with postcolumn infusion.

Prefilled plastic packaging is time- and cost-effective in hospital pharmacy because it prevents waste, preparation errors, dosage errors, microbial contamination and accidents. This packaging mostly includes prefilled syringes (PFS), intravenous (IV) bags and vials intended for long-term storage that can be used for immediate treatment. There is a rising availability in the market for prefilled drug products due to their practical approach. Leachable compounds could be evaluated in hospital pharmacy-prepared prefilled drug solutions. The Pharmacy Department at the Lausanne University Hospital has developed an innovative, highly sensitive, and generic method by postcolumn infusion based on ultrahigh-performance liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS) for the analysis of plastic additives in hospital pharmacies. The postcolumn infusion solution was developed with 2% ammonium hydroxide in methanol on a representative set of 30 candidate compounds with different physical-chemical properties, such as log P and molecular structure, to represent the most important categories of additives. The LODs obtained for all compounds ranged from 0.03 to 7.91 ng/mL with linearity up to 250 ng/mL. Through this screening method, plastic additives can be rapidly identified due to the combined use of retention time, exact mass (including isotopic pattern) and MS/MS spectra. In addition, the users can screen for vast categories of plastic additives, including plasticizers, epoxy monomers, antioxidants, UV stabilizers, and others. The screening is facilitated by assessments of a complex in-house-built database for extractable and leachable trace assessment (DELTA), containing 205 compounds for unambiguous identification. Relative response factors were established for all analytes to obtain a semiquantitation of compounds. Moreover, the database also contains valuable estimative toxicology information, which was obtained through calculating their permissible dose exposure threshold; thus, estimative toxicology assessment can be performed for identified compounds in prefilled drug products. This method and the database were applied to a hospital pharmacy-prepared prefilled vancomycin syringe for paediatric use. Ultrasound-assisted dispersive liquid-liquid microextraction (UA-DLLME) was used to prepare the samples for leachable analysis. As a result, 17 plastic additives were formally identified, and their concentrations were estimated. A toxicology assessment was performed by comparing their concentrations with their theoretical PDE thresholds. In conclusion, the prefilled drug solution released a negligible amount of known leachables that appeared to be safe for use in neonates and children.

Dry alginate beads for fecal microbiota transplantation: From model strains to fecal samples.

Clostridioides difficile infection (CDI) is a critical nosocomial infection with more than 124,000 cases per year in Europe and a mortality rate of 15-17 %. The standard of care (SoC) is antibiotic treatment. Unfortunately, the relapse rate is high (∼35 %) and SoC is significantly less effective against recurrent infection (rCDI). Fecal microbiota transplantation (FMT) is a recommended treatment against rCDI from the second recurrence episode and has an efficacy of 90 %. The formulation of diluted donor stool deserves innovation because its actual administration routes deserve optimization (naso-duodenal/jejunal tubes, colonoscopy, enema or several voluminous oral capsules). Encapsulation of model bacteria strains in gel beads were first investigated. Then, the encapsulation method was applied to diluted stools. Robust spherical gel beads were obtained. The mean particle size was around 2 mm. A high loading of viable microorganisms was obtained for model strains and fecal samples. For plate-counting, values ranged from 1015 to 1017 CFU/g for single and mixed model strains, and 106 to 108 CFU/g for fecal samples. This corresponded to a viability of 30 % to 60 % as assessed by flow cytometry. This novel formulation is promising as the technology is applicable to both model strains and bacteria contained in the gut microbiota.

Wipe sampling procedure coupled to LC-MS/MS analysis for the simultaneous determination of 10 cytotoxic drugs on different surfaces.

A simple wipe sampling procedure was developed for the surface contamination determination of ten cytotoxic drugs: cytarabine, gemcitabine, methotrexate, etoposide phosphate, cyclophosphamide, ifosfamide, irinotecan, doxorubicin, epirubicin and vincristine. Wiping was performed using Whatman filter paper on different surfaces such as stainless steel, polypropylene, polystyrol, glass, latex gloves, computer mouse and coated paperboard. Wiping and desorption procedures were investigated: The same solution containing 20% acetonitrile and 0.1% formic acid in water gave the best results. After ultrasonic desorption and then centrifugation, samples were analysed by a validated liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) in selected reaction monitoring mode. The whole analytical strategy from wipe sampling to LC-MS/MS analysis was evaluated to determine quantitative performance. The lowest limit of quantification of 10 ng per wiping sample (i.e. 0.1 ng cm(-2)) was determined for the ten investigated cytotoxic drugs. Relative standard deviation for intermediate precision was always inferior to 20%. As recovery was dependent on the tested surface for each drug, a correction factor was determined and applied for real samples. The method was then successfully applied at the cytotoxic production unit of the Geneva University Hospitals pharmacy.

Exploring the Reasons Behind the Substantial Discontinuation Rate Among Patients Taking CT-P13 in a Large Tertiary Hospital in Western Switzerland: A Retrospective Cohort Study Using Routinely Collected Medical Data.

BACKGROUND: CT-P13 is an infliximab biosimilar that was granted market authorization in Switzerland in 2016. Despite the growing literature supporting the equivalence of CT-P13 compared with originator infliximab regarding the efficacy, safety, and immunogenicity and the undeniable cost-saving opportunities, CT-P13 remains widely underused in Switzerland. OBJECTIVE: Leaving aside the phenomenon of a low initiation rate, this study aimed to explore the reasons behind the high discontinuation rate observed among the patients taking CT-P13 in a large tertiary hospital in Western Switzerland. METHODS: We performed a retrospective cohort study using routinely collected data. Patients were eligible if they received originator infliximab or CT-P13 between September 2017 and December 2020. They were included if they had received at least two CT-P13 infusions during the same period. Patients were excluded if the follow-up was incomplete prior to or 6 months after their first CT-P13 infusion and if they had an oncological main diagnosis. Primary outcomes were the reasons for treatment discontinuation. RESULTS: One hundred and fifty-six patients were included and classified into two groups: switchers who were treated with originator infliximab and were switched to CT-P13 (n = 85, 54%) and initiators who did not receive originator infliximab prior to CT-P13 treatment (n = 71, 46%). Included patients belonged to three different groups of diagnosis: gastroenterological (67, 43%), rheumatological (61, 39%), and immunological (28, 18%). Twenty-three (27%) switchers and 35 (49%) initiators discontinued CT-P13 after 12 months. Main reasons for CT-P13 discontinuation were lack of efficacy (n = 21, 36%) and secondary loss of response (n = 16, 28%); however, objective assessments were not available. Initiators' probability to discontinue CT-P13 at 12 months was significantly higher than switchers' (p < 0.01). CONCLUSIONS: Lack of efficacy and secondary loss of response were the main reasons for the high CT-P13 discontinuation rate observed in a large tertiary hospital in Western Switzerland. Lack of active training and coordination among healthcare professionals and little education in patients may have exacerbated patients' subjective complaints and increased the CT-P13 discontinuation rate.

Current Expertise, Opinions, and Attitude toward TNF-⍺ Antagonist Biosimilars among Physicians: A Self-Administered Online Survey in Western Switzerland.

Tumor necrosis factor-alpha (TNF-⍺) antagonists are biological drugs with multiple authorized biosimilars. Biosimilars are becoming critical to the financial sustainability of health systems. Recent studies emphasize that physicians' knowledge regarding biosimilars has not yet progressed sufficiently to overcome their concerns regarding biosimilars' safety and efficacy. To assess the current knowledge, opinions, and attitudes toward TNF-⍺ antagonist biosimilars among postgraduate physicians and specialists, an anonymous, self-administered survey was implemented on SurveyMonkey between February and May 2022. The survey was validated through think-aloud interviews with senior and postgraduate physicians in rheumatology, gastroenterology, and immunoallergology, and a senior epidemiologist. Participant recruitment was conducted with the help of the physicians' professional societies and departmental head physicians of two university hospitals in Western Switzerland. Most physicians felt more comfortable initiating a TNF-⍺ antagonist biosimilar in biologic-naive patients (BNPs) than switching patients stabilized on the original biologic (originator). However, most participants agreed that BNPs should start treatment with the biosimilar rather than the originator when available. Postgraduate physicians and specialists in rheumatology, gastroenterology, and immunoallergology who participated in this survey were familiar with TNF-⍺ antagonist biosimilars and were confident in prescribing them. Yet, they still preferred to avoid switching a patient already on the originator.

Off-label use of psychotropic drugs in a Swiss paediatric service: similar results from two different cohort studies.

BACKGROUND: The high off-label use of drugs in paediatric patients raises questions on the efficacy and safety when prescribing psychotropic drugs. In our studies, we aimed to characterise the use of psychotropic drugs in the paediatric service of a tertiary hospital and quantify the proportion of off-label prescriptions with respect to age, indication and dosage recommendations approved in Switzerland, France and the USA. METHODS: We conducted a retrospective cohort study (RCS) that included hospitalised patients from 1 December 2017, to 28 June 2018 with at least one PD prescription (n = 74) and a prospective cohort study (PCS) that included those hospitalised from 29 June 2018, to 30 November 2018 with at least one psychotropic drug prescription (n = 37). For both studies, we collected demographic, medical and medication data. Off-label prescriptions were identified by comparing the marketing authorisations published in the three selected countries. RESULTS: The average age of RCS and PCS patients were 13 ± 3 years and 14 ± 2 years, respectively. Of the 168 and 86 psychotropic prescriptions collected in the RCS and PCS, respectively, 70% and 71% prescriptions were off-label based on Swiss marketing authorisations. These rates declined when compared with French marketing authorisations (61% and 67% prescriptions) and were significantly lower when compared with American marketing authorisations (56% and 51% prescriptions). Psychotropic drugs were often prescribed as needed in both studies (53% and 43% of prescriptions), with only half of the patients actually receiving one of these prescribed psychotropic drugs. CONCLUSION: Our results showed a high proportion of off-label prescriptions of psychotropic drugs in a hospital setting. The off-label prescription rates according to Swiss marketing authorisations were the highest when compared with French and American marketing authorisations. Harmonisation of either international marketing authorisations or dosage recommendations at a national level could be a step forward to improved and evidence-based use of psychotropic drugs in children and adolescents.

Pharmacists' considerations on non-medical switching at the hospital: a systematic review of the economic outcomes of cost-saving therapeutic drug classes.

OBJECTIVES: Non-medical switching (NMS) strategies have the capacity to reduce overall costs in hospitals while maintaining a high level of care. However, the most appropriate diseases and/or medicines for NMS strategies are still vague. The aim of this review was to give a state-of-the-art summary regarding the economic outcomes resulting from the use of NMS strategies and to discuss whether they would be implementable in a hospital inpatient setting. METHODS: A systematic literature search was conducted in Medline, Embase, and ScienceDirect. Studies published between 1988 and 2018 were included if they evaluated the economic impact of NMS strategies or if they performed an economic evaluation between two drugs. Studies regarding antineoplastic agents, endocrine therapies, and immunostimulants, or immunosuppressants, and biosimilars were excluded. RESULTS: Fifty (69%) studies assessing an NMS strategy and 22 (31%) studies comparing two medicines were allocated to four categories: prospective studies (n=8, 11%); retrospective chart reviews (n=29, 40%); retrospective claims analysis (n=13, 18%); and retrospective data analysis (n=22, 31%). Hypercholesterolemia, peptic ulcer, and gastro-oesophageal reflux diseases, diabetes mellitus, and venous thromboembolism were the most prevalent diseases in studies evaluating an NMS strategy. Sixty-eight per cent of the included papers reported a reduction in costs with no significant changes in health outcomes and 8 per cent reported a deterioration in health outcomes and/or increased costs. CONCLUSION: Regardless of the exclusion of studies regarding biologics or medicines used in oncology, the review highlights that NMS strategies with medicines whose management do not require a thorough clinical assessment were associated with reduced costs and no significant changes in patients' health outcomes, in the inpatient setting. NMS strategies targeting medicines that require an extensive clinical assessment should be evaluated using hospital-specific effectiveness and/or utility data prior to their implementation.

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.

Simultaneous quantification of ten cytotoxic drugs by a validated LC-ESI-MS/MS method.

A liquid chromatography separation with electrospray ionisation and tandem mass spectrometry detection method was developed for the simultaneous quantification of ten commonly handled cytotoxic drugs in a hospital pharmacy. These cytotoxic drugs are cytarabine, gemcitabine, methotrexate, etoposide phosphate, cyclophosphamide, ifosfamide, irinotecan, doxorubicin, epirubicin and vincristine. The chromatographic separation was carried out by RPLC in less than 21 min, applying a gradient elution of water and acetonitrile in the presence of 0.1% formic acid. MS/MS was performed on a triple quadrupole in selected reaction monitoring mode. The analytical method was validated to determine the limit of quantification (LOQ) and quantitative performance: lowest LOQs were between 0.25 and 2 ng mL(-1) for the ten investigated cytotoxic drugs; trueness values (i.e. recovery) were between 85% and 110%, and relative standard deviations for both repeatability and intermediate precision were always inferior to 15%. The multi-compound method was successfully applied for the quality control of pharmaceutical formulations and for analyses of spiked samples on potentially contaminated surfaces.