Population pharmacokinetics of ganciclovir and valganciclovir in paediatric solid organ and stem cell transplant recipients.

AIMS: Ganciclovir (GCV) and its prodrug valganciclovir (VGCV) are first-line agents to prevent and treat cytomegalovirus in transplant recipients. There is high pharmacokinetic (PK) interindividual variability and PK data are scarce, especially in paediatric stem cell transplant (SCT) recipients. We sought to determine the optimal GCV and VGCV dosing in transplanted children. METHODS: We conducted a single-centre retrospective population PK (POPPK) study of IV GCV and enteral VGCV in paediatric solid organ transplant (SOT) and SCT recipients. We included children who were transplanted and had available plasma GCV concentrations, done per standard of care. POPPK analysis was performed using a nonlinear mixed effects modelling approach with NONMEM. Optimal dosing was determined based on the achievement of the surrogate efficacy target: GCV 24 h area under the concentration-time curve (AUC0-24h ) of 40-60 mg.h.L-1 . RESULTS: Fifty children with a median [range] age of 7.5 years [0.5-17.4] contributed 580 PK samples. A two-compartment model with first-order absorption with a lag time and first-order elimination fit the data well. Creatinine clearance and body weight (WT) were significant covariates for GCV clearance (CL); and WT for the volumes of distribution. IV GCV 15-20 mg.kg-1 .day-1 divided every 12 hours achieved the highest probability of target achievement (PTA) (33.0-33.8%). Enteral VGCV 30 and 40 mg.kg-1 .day-1 divided every 12 hours in children 0-<6 years, and 6-18 years, respectively, achieved the highest PTA (29.1-33.0%). CONCLUSION: This is the first POPPK model developed in children with either SOT or SCT. Concentration target achievement was low, suggesting a potential benefit for therapeutic drug monitoring to ensure optimal exposure.

Analyse des modes de défaillance, de leurs effets et de leur criticité dans le circuit du médicament: revue de littérature.

BACKGROUND: Failure mode, effects, and criticality analysis (FMECA) is a systematic and proactive risk analysis method to determine major failures in complex processes. OBJECTIVE: To identify all articles involving the use of failure mode and effects analysis (FMEA), FMECA, or FMECA in health care within the medication use system. DATA SOURCES STUDY SELECTION AND DATA EXTRACTION: The MEDLINE database was searched, for the period January 1990 to January 2017. The search included studies using the FMECA method, in part or in full, and dealing with one or several components of the medication use system. The reference lists of articles identified in the initial search were checked manually for additional pertinent references. DATA SYNTHESIS: The researchers identified 171 articles, and retained 39 for analysis: 32 describing use of the FMEA or FMECA approach and 7 describing use of the FMECA in health care approach. They identified between 4 to 378 failure modes, according to the published studies. Among the 39 articles, 10 reported a pre- and post-implementation analysis of corrective measures. In 4 of those 10 articles, the analysis was conducted on a theoretical basis, that is, before the corrective measures were actually implemented. Using the articles retained for analysis, a summary table was developed with the following elements: publication year, main author, country, primary objective, secondary objectives, descriptions of both method and results, and comments. The summary table gave the opportunity to comment on the use of the FMECA-type analysis within the medication use system. CONCLUSIONS: This literature review included 39 published articles using an FMEA, FMECA, or FMECA in health care approach within the medication use system. Most studies used either the FMEA or the FMECA approach, whereas the FMECA in health care approach was used only rarely. Only a minority of studies assessed the effects of corrective measures that were implemented. This overall approach allows for mapping of a care process, determination of failure modes, and prioritization of corrective measures. Its use for the assessment of the medication use system should be promoted.

Failure Mode, Effect, and Criticality Analysis of the Parenteral Nutrition Process in a Mother-Child Hospital: The AMELIORE Study.

BACKGROUND: The parenteral nutrition (PN) process is complex and involves multiple steps and substeps, especially in pediatrics and neonatology, given the particular needs of these patients. The objective of this study was to perform a critical analysis of the PN process at the Centre Hospitalier Universitaire Sainte-Justine to determine which potential pitfalls are related to this process and which should be prioritized when implementing corrective measures. METHODS: This is a Failure Mode, Effect, and Criticality Analysis (FMECA) study. A multidisciplinary team assessed each step of the PN process and identified associated failure modes. Adapted rating scales were used to determine severity, frequency, and detectability of the failure modes. Ratings were established through multidisplinary consensus, and a criticality index (CI) was calculated for each failure mode. RESULTS: A total of 265 failure modes were identified in the 5 major steps of the PN process. The failure mode with the highest CI was the inscription of an inaccurate weight at prescription, with a CI of 800. The step with the highest cumulative CIs was administration to patients, with a CI sum of 7691. Various recommendations aimed at minimizing the risks associated with the PN process were made following this FMECA. Additional interventions are expected to emanate from this project because data will be presented throughout the departments involved. CONCLUSION: This study is a successful example for other hospitals interested in carrying out the same kind of healthcare improvement initiative.