Search

Background: Primary infection with or reactivation of Epstein- Barr virus (EBV) can occur after liver transplant (LT) and can lead to posttransplant lymphoproliferative disease (PTLD). In pediatric LT, an EBV-DNA viral load (EBV VL) monitoring strategy, including the reduction of immunosuppression, has led to a lower incidence of PTLD. For adult LT recipients with less primary infection and more EBV reactivation, it is unknown whether this strategy is effective. Objective: To examine the effect of an EBV VL monitoring strategy on the incidence of PTLD after LT in adults. Design: Cohort study. Setting: Two university medical centers in the Netherlands. Patients: Adult recipients of first LT in Leiden between September 2003 and January 2017 with an EBV VL monitoring strategy formed the monitoring group (M1), recipients of first LT in Rotterdam between January 2003 and January 2017 without such a strategy formed the contemporary control group (C1), and those who had transplants in Leiden between September 1992 and September 2003 or Rotterdam between 1986 and January 2003 formed the historical control groups (M0 and C0, respectively). Measurements: Influence of EBV VL monitoring on incidence of PTLD. Results: After inverse probability of treatment weighting of the 4 groups to achieve a balance among the groups for important patient characteristics, differences within hospitals between the historical and recent era in cumulative incidences & mdash; expressed as the number of events per 1000 patients measured at 5-, 10-, and 15-year follow-up & mdash;showed fewer events in the contemporary era in both centers. This difference was considerably larger in the monitoring center, whereas the 95% CI included the null value of 0 for point estimates. Limitation: Retrospective, low statistical power, and incompletely balanced groups, and non-EBV PTLD cannot be prevented. Conclusion: Monitoring EBV VL may reduce PTLD incidence after LT in adults; larger studies are warranted.

IntroductionMultiple choice questions (MCQs) offer high reliability and easy machine-marking, but allow for cueing and stimulate recognition-based learning. Very short answer questions (VSAQs) may circumvent these limitations. We investigated VSAQ reliability, discriminative capability, acceptability, and knowledge retention compared to MCQs.MethodsDutch undergraduate medical students (n=375) were randomised to a formative exam with VSAQs first and MCQs second or vice versa in two courses, to determine reliability and discrimination. Next, acceptability (i.e., VSAQ review time) was determined in the summative exam. Knowledge retention at 2 and 5 months was determined by comparing score increase on the three-monthly progress test (PT) between students tested with VSAQs and students from previous years tested without VSAQs.ResultsReliability (Cronbach’s α) was 0.74 for VSAQs and 0.57 for MCQs in one course. In the other course, Cronbach’s α was 0.87 for VSAQs and 0.83 for MCQs. Discrimination (Rir) was 0.27 vs. 0.17 and 0.43 vs. 0.39 for VSAQs vs. MCQs, respectively. Reviewing time of one VSAQ for the entire student cohort was ±2 minutes on average. No clear effect on knowledge retention after 2 and 5 months was observed.DiscussionWe found increased reliability and discrimination of VSAQs compared to MCQs. Reviewing time of VSAQs was acceptable. The association with knowledge retention was unclear in our study. This study supports and extends positive results of previous studies on VSAQs regarding reliability, discriminative capability, and acceptability in Dutch undergraduate medical students.

Background At the most severe end of the spectrum of congenital heart disease are patients with an univentricular physiology. They comprise a heterogeneous group of congenital heart malformations that have the common characteristic that the cardiac morphology is not equipped for sustaining a biventricular circulation. Case summary Here, we present a case of an adult patient after Fontan palliation, illustrative of the complex clinical course and the broad spectrum of complications that can be encountered during follow-up, highlighting the need for a multidisciplinary approach in the clinical care for these patients. Discussion During the surgical Fontan procedure, the inferior vena cava is connected to the pulmonary circulation, after prior connection of the superior vena cava to the pulmonary arterial circulation. The resulting cavopulmonary connection, thus lacking a subpulmonic ventricle, provides non-pulsatile passive flow of oxygen-poor blood from the systemic venous circulation into the lungs, and the functional monoventricle pumps the oxygen-rich pulmonary venous return blood into the aorta. With an operative mortality of Conclusion For optimal treatment, the evaluation in a multidisciplinary team is mandatory, using the specific expertise of the team members to timely detect and address late complications and to support quality of life.

Aims Meltdose tacrolimus (Envarsus) is marketed as a formulation with a more consistent exposure. Due to the narrow therapeutic window, therapeutic drug monitoring is essential to maintain adequate exposure. The primary objective of this study was to develop a population pharmacokinetic (PK) model of Envarsus among liver transplant patients and select a limited sampling strategy (LSS) for AUC estimation. The secondary objective was to investigate potential covariates including CYP3A/IL genotype suitable for initial dose optimization when converting to Envarsus. Methods Adult liver transplant patients were converted from prolonged release tacrolimus (Advagraf) to Envarsus and blood samples were obtained using whole blood and dried blood spot sampling. Subsequently the population PK parameters were estimated using nonlinear‐mixed effect modelling. Demographic factors, and recipient and donor CYP3A4, CYP3A5, IL‐6, ‐10 and ‐18 genotype were tested as potential covariates to explain interindividual variability. Results Fifty‐five patients were included. A 2‐compartment model with delayed absorption was the most suitable to describe population PK parameters. The population PK parameters were as follows: clearance, 3.27 L/h; intercompartmental clearance, 9.6 L/h; volume of distribution of compartments 1 and 2, 95 and 500 L, respectively. No covariates were found to significantly decrease interindividual variability. The best 3‐point LSS was t = 0,4,8 with a median bias of 1.8% (−12.5–12.5). Conclusions The LSS can be used to adequately predict the AUC. No clinically relevant covariates known to influence the PK of Envarsus, including CYP3A status, were identified and therefore do not seem useful for initial dose optimization.