Busulfan exposure associated with event-free survival in children after allogeneic haematopoietic stem cell transplantation: A retrospective multicenter cohort study

Busulfan exposure associated with event-free survival in children after allogeneic haematopoietic stem cell transplantation: A retrospective multicenter cohort study OBJECTIVE To determine the relationship between busulfan cumulative area under the curve (AUC] and event-free survival lEFS] in children undergoing allogeneic haematopoietic stem cell transplantation (alloHCT). DESIGN Retrospective, multicenter cohort study. METHODS Children who underwent alloHCT in 15 different centres worldwide were included in this study (2000-20131. Participants had to be on intravenous busulfan and pharmacokinetic samples had to be available. Exposure of interest was the cumulative AUC of busulfan, and primary outcome was EFS (time to graft failure, relapse or all-cause mortality). Cox regression models were used to derive relative risks (RR), and the optimal busulfan AUC level was estimated using propensity adjusted Weibull models. RESULTS A total of 674 subjects (41[%] malignant, 59[%] non- malignant) with a median age of 4.5 years (interquartile range 1.4-10.7 years) were included in the analysis. We observed a significant U-shaped relationship between busulfan cumulative AUC and EFS (P = 0.011). The optimal target was estimated at 90 mgh/L (78-101 mgh/L), and was independent of any of the investigated patient characteristics. An AUC below the target increased the risk of graft failure and relapse (relative risk 1.75, P = 0.004), while transplant-related mortality was more pronounced when the AUC was too high (relative risk 2.99, P <0.0011. CONCLUSION This is the largest study on the relationship between busulfan and clinical outcomes in children undergoing alloHCT. Our results strongly advocate the use of therapeutic drug monitoring of busulfan, using 90 mg-h/L (78-101 mg h/L) as a target

Guidance by physicians and pharmacists during antidepressant therapy: patients' needs and suggestions for improvement

OBJECTIVE Guidance of patients treated with antidepressants is paramount for successful therapy. The aim was to assess patients' needs and suggestions for improvement of guidance by physicians and pharmacists during second generation antidepressant (SGA) therapy. DESIGN Five focus group discussions were held with a total of 34 patients using an SGA. METHODS The discussions were conducted flexibly and responsrvely using a semistructured topic list. All focus group discussions were video-recorded and transcripts were analysed using ATLAS.ti for coding, thematic and open analysis. RESULTS Participants stated they were in need of better guidance. They suggested improving content of information during decisional moments, patient-health care professional communication and communication in-between health care professionals, and finally, organisation of guidance. Barriers to achieving improved guidance were cited. CONCLUSION Content, communication and organisation of guidance are pivotal for achieving optimal guidance. Participants mentioned that their current experienced guidance had limitations and brought up solutions for improvement. A next step would be to discuss the suggested solutions with health care professionals to assess their views and to discuss the possibility for implementation. After implementation, future studies could be aimed at determination of its impact on patients' treatment efficacy, quality of life, treatment satisfaction and healthcare costs

Drug waste of ready-to-administer syringes in the intensive care unit: Aseptically prepared syringes versus prefilled sterilized syringes

Background: The availability of ready-to-administer (RTA) syringes for intravenous (IV) drugs facilitates rapid and safe administration in emergency and intensive care situations. Hospital pharmacies can prepare RTA syringes through aseptic batchwise filling. Due to excess production of these RTA syringes for sufficient availability for patient care and their limited (microbiological) shelf-life, waste is unavoidable, which contributes to environmental pollution. RTA prefilled sterilized syringes (PFSSs) have much longer shelf-lives than aseptically prepared RTA syringes and might contribute to reducing drug waste. Aim: This study aimed to evaluate the difference in drug waste between RTA syringes that were prepared through aseptic batchwise filling and RTA PFSSs in the Intensive Care Unit (ICU). Methods: We measured drug waste of RTA syringes over an 8-year time period from August 2015 to May 2023 in the 32-bed ICU of the University Medical Center Utrecht. We distinguished between RTA syringes prepared through aseptic batchwise filling by our hospital pharmacy (“RTA aseptic syringes”, shelf-life of 31 days) and RTA PFSSs (shelf-life of 18 months). An intervention group of three drug products that were replaced by PFSSs was compared to a control group of five drug products that were not replaced by PFSSs during the study period. We then defined four different periods within the total study period, based on quarantine time of the RTA aseptic syringes and time of PFSS introduction: 1) no quarantine, 2) 3-day quarantine, 3) 7-day quarantine and 4) PFSS introduction. Our primary endpoint was the number of RTA syringes that was wasted, expressed as the percentage of the total number of syringes dispensed to the ICU in each of these four periods. We used a Kruskall-Wallis test to test if waste percentages differed between time periods in the control and intervention groups, with a post-hoc Dunn's test for pairwise comparisons. Furthermore, we applied two interrupted time series (ITS) analyses to visualize and test the effect of introducing different quarantine times and the PFSSs on waste percentage. Results: Introduction of PFSSs significantly decreased drug waste of RTA syringes irrespective of drug type in the intervention group, from 31% during the 7-day quarantine period to 5% after introduction of the PFSS (p<0.001). The control group showed no significant decrease in drug waste over the same time periods (from 20% to 16%; p=0.726). We observed a significant difference in the total drug waste of RTA aseptic syringes between time periods, which may be attributed to the implementation of different quality control quarantine procedures. The ITS model of the intervention group showed a direct decrease of 17.7% in waste percentage after the introduction of PFSSs (p=0.083). Conclusion: Drug waste of RTA syringes for the ICU can be significantly decreased by introducing PFSSs, supporting hospitals to enhance environmental sustainability. Furthermore, the waste percentage of RTA syringes prepared through aseptic batchwise filling is significantly impacted by duration of quarantine time

Detectability of Medication Errors With a STOPP/START-Based Medication Review in Older People Prior to a Potentially Preventable Drug-Related Hospital Admission.

INTRODUCTION Multimorbidity and polypharmacy are risk factors for drug-related hospital admissions (DRAs) in the ageing population. DRAs caused by medication errors (MEs) are considered potentially preventable. The STOPP/START criteria were developed to detect potential MEs in older people. OBJECTIVE The aim of this study was to assess the detectability of MEs with a STOPP/START-based in-hospital medication review in older people with polypharmacy and multimorbidity prior to a potentially preventable DRA. METHODS Hospitalised older patients (n = 963) with polypharmacy and multimorbidity from the intervention arm of the OPERAM trial received a STOPP/START-based in-hospital medication review by a pharmacotherapy team. Readmissions within 1 year after the in-hospital medication review were adjudicated for drug-relatedness. A retrospective assessment was performed to determine whether MEs identified at the first DRA were detectable during the in-hospital medication review. RESULTS In total, 84 of 963 OPERAM intervention patients (8.7%) were readmitted with a potentially preventable DRA, of which 72 patients (n = 77 MEs) were eligible for analysis. About half (48%, n = 37/77) of the MEs were not present during the in-hospital medication review and therefore were not detectable at that time. The pharmacotherapy team recommended a change in medication regimen in 50% (n = 20/40) of present MEs, which corresponds to 26% (n = 20/77) of the total identified MEs at readmission. However, these recommendations were not implemented. CONCLUSION MEs identified at readmission were not addressed by a prior single in-hospital medication review because either these MEs occurred after the medication review (~50%), or no recommendation was given during the medication review (~25%), or the recommendation was not implemented (~25%). Future research should focus on optimisation of the timing and frequency of medication review and the implementation of proposed medication recommendations. REGISTRATION ClinicalTrials.gov identifier: NCT02986425. December 8, 2016. FUNDING European Union HORIZON 2020, Swiss State Secretariat for Education, Research and Innovation (SERI), Swiss National Science Foundation (SNSF)

Busulfan target exposure attainment in children undergoing allogeneic hematopoietic cell transplantation: a single day versus a multiday therapeutic drug monitoring regimen

Busulfan exposure has previously been linked to clinical outcomes, hence the need for therapeutic drug monitoring (TDM). Study objective was to evaluate the effect of day 1 TDM-guided dosing (regimen d1) versus days 1 + 2 TDM-guided dosing (regimen d1 + 2) on attaining adequate busulfan exposure. In this observational study, we included all children receiving busulfan-based allogeneic hematopoietic cell transplantation. Primary outcome was the percentage of patients achieving busulfan target attainment in both TDM regimens. Secondary outcomes were the variance in busulfan exposure and day-4 clearance (Clday4) estimates between both TDM regimens and dosing day 1 and 2. In regimen d1, 84.3% (n = 91/108) attained a therapeutic busulfan exposure, while in regimen d1 + 2 a proportion of 90.9% was found (n = 30/33, not-significant). Variance of Clday4 estimate based on busulfan day 2 concentrations was significantly smaller than the variance of Clday4 estimates based on day 1 concentrations (p < 0.001). Therefore, day 1-guided TDM (pharmacometric model-based) of busulfan may be sufficient for attaining optimal target exposure, provided that subsequent TDM is carried out if required. However, performing TDM on subsequent days may be beneficial, as measurements on day 2 seemed to reduce the variance in the estimated clearance as compared to day 1 sampling

Detectability of Medication Errors With a STOPP/START-Based Medication Review in Older People Prior to a Potentially Preventable Drug-Related Hospital Admission

Introduction Multimorbidity and polypharmacy are risk factors for drug-related hospital admissions (DRAs) in the ageing population. DRAs caused by medication errors (MEs) are considered potentially preventable. The STOPP/START criteria were developed to detect potential MEs in older people.Objective The aim of this study was to assess the detectability of MEs with a STOPP/START-based in-hospital medication review in older people with polypharmacy and multimorbidity prior to a potentially preventable DRA.Methods Hospitalised older patients (n = 963) with polypharmacy and multimorbidity from the intervention arm of the OPERAM trial received a STOPP/START-based in-hospital medication review by a pharmacotherapy team. Readmissions within 1 year after the in- hospital medication review were adjudicated for drug-relatedness. A retrospective assessment was performed to determine whether MEs identified at the first DRA were detectable during the in-hospital medication review.Results In total, 84 of 963 OPERAM intervention patients ( 8.7%) were readmitted with a potentially preventable DRA, of which 72 patients (n = 77 MEs) were eligible for analysis. About half (48%, n = 37/77) of the MEs were not present during the in-hospital medication review and therefore were not detectable at that time. The pharmacotherapy team recommended a change in medication regimen in 50% ( n = 20/40) of present MEs, which corresponds to 26% (n = 20/77) of the total identified MEs at readmission. However, these recommendations were not implemented.Conclusion MEs identified at readmission were not addressed by a prior single in-hospital medication review because either these MEs occurred after the medication review (similar to 50%), or no recommendation was given during the medication review (similar to 25%), or the recommendation was not implemented (similar to 25%). Future research should focus on optimisation of the timing and frequency of medication review and the implementation of proposed medication recommendations

Regulatory Safety Learning Driven by the Mechanism of Action: The Case of TNF-alpha Inhibitors: The Case of TNF-α Inhibitors

The summary of product characteristics (SmPCs) is an important information source that includes the adverse drug reactions (ADRs) associated with the drug. Drugs with the same mechanism of action are expected to have a similar ADR profile and thus a substantial overlap of the described ADRs in the SmPC. The objective of this study is to assess this overlap. We extracted all ADRs (excluding hypersensitivity and administration site reactions) that were described in the first and all subsequent versions of the SmPCs of all approved TNF-α inhibitors in the European Union. The Medical Dictionary for Regulatory Activities was used to characterize the ADRs. At the end of follow-up, 293 unique ADRs (at high level term level) were described in the SmPCs of the 5 TNF-α inhibitors. There was substantial variation in the number of ADRs described in the SmPC among the TNF-α inhibitors. Of the 293 ADRs, 133 (45%) were described in the SmPC of one TNF-α inhibitor and 39 (13%) in the SmPCs of all 5 TNF-α inhibitors. Serious ADRs and ADRs classified as important risks were described approximately four times more often in a second SmPC than ADRs not classified as such. In conclusion, the ADRs described in the SmPCs of the TNF-α inhibitors differ considerably in number and type. In order to adequately inform prescribers and patients, acquired knowledge of the safety profile of drugs with the same mechanism of action should increasingly be taken into account in the assessment of all drugs within the class

Possible consequences for quality and effectiveness: Keeping medicines at home often does not go well

Patiënten bewaren geneesmiddelen thuis vaak niet volgens de aanbevolen condities. Ook worden middelen bewaard waarvan de houdbaarheidsdatum al is verstreken. Dit kan leiden tot een afname in kwaliteit en kan van invloed zijn op de veiligheid en werkzaamheid. Patiënten, apothekers, overheid en fabrikanten moeten zich gezamenlijk inspannen om deze problematiek het hoofd te bieden, stelt Niels Vlieland

Associations between personality traits and adequate home storage of drugs in older patients

The objective of this study was to investigate the association between personality traits of older patients and adequate home storage of drugs. Forty-four participating Dutch community pharmacists randomly selected each up to four community-dwelling elderly patients (≥65 years) who were using at least one prescription drug. The Big Five Inventory was used to assess the personality traits–‘openness’, ‘conscientiousness’, ‘extraversion’, ‘agreeableness’ and ‘neuroticism’–of patients. An assessment of adequate home storage of drugs was made using a summed composite score for each patient ranging from zero (adequate storage) to three (inadequate storage) was based on storage criteria representing quality, information and level of storage organization. A 51.2% of the patients stored drugs adequately in accordance with all quality (“Q“) and information (“I“) criteria. A high level of drug storage organization was found in 70.8% of patients. Forty-three patients (31.4%) stored their drugs adequately based on all storage criteria (composite storage score 0). No associations between personality dimensions and adequate drug storage were found. Having a lower number of drugs was associated with adequate drug home storage (ORadjusted 0.86; 95% CI: 0.77–0.96). In conclusion, this study suggests that personality is not associated with adequate home storage of drugs in older patients

Associations between personality traits and adequate home storage of drugs in older patients

The objective of this study was to investigate the association between personality traits of older patients and adequate home storage of drugs. Forty-four participating Dutch community pharmacists randomly selected each up to four community-dwelling elderly patients (≥65 years) who were using at least one prescription drug. The Big Five Inventory was used to assess the personality traits–‘openness’, ‘conscientiousness’, ‘extraversion’, ‘agreeableness’ and ‘neuroticism’–of patients. An assessment of adequate home storage of drugs was made using a summed composite score for each patient ranging from zero (adequate storage) to three (inadequate storage) was based on storage criteria representing quality, information and level of storage organization. A 51.2% of the patients stored drugs adequately in accordance with all quality (“Q“) and information (“I“) criteria. A high level of drug storage organization was found in 70.8% of patients. Forty-three patients (31.4%) stored their drugs adequately based on all storage criteria (composite storage score 0). No associations between personality dimensions and adequate drug storage were found. Having a lower number of drugs was associated with adequate drug home storage (ORadjusted 0.86; 95% CI: 0.77–0.96). In conclusion, this study suggests that personality is not associated with adequate home storage of drugs in older patients