Fludarabine is a nucleoside analog with antileukemic and immunosuppressive activity commonly used in allogeneic hematopoietic cell transplantation (HCT). Several fludarabine population pharmacokinetic (popPK) and pharmacodynamic models have been published enabling the movement towards precision dosing of fludarabine in pediatric HCT; however, developed models have not been validated in a prospective cohort of patients. In this multicenter pharmacokinetic study, fludarabine plasma concentrations were collected via a sparse-sampling strategy. A fludarabine popPK model was evaluated and refined using standard nonlinear mixed effects modelling techniques. The previously described fludarabine popPK model well-predicted the prospective fludarabine plasma concentrations. Individuals who received model-based dosing (MBD) of fludarabine achieved significantly more precise overall exposure of fludarabine. The fludarabine popPK model was further improved by both the inclusion of fat-free mass instead of total body weight and a maturation function on fludarabine clearance. The refined popPK model is expected to improve dosing recommendations for children younger than 2 years and patients with higher body mass index. Given the consistency of fludarabine clearance and exposure across its multiple days of administration, therapeutic drug monitoring is not likely to improve targeted exposure attainment.

Hallucination simulations improve student empathy but increase desired social distance from individuals with schizophrenia, while direct contact reduces social distance. This study describes the implementation of combining an auditory hallucination simulation with a speaker diagnosed with schizophrenia and its impact on mental illness stigma. Pharmacy students in their last year of didactic instruction (N = 346) attended a presentation by a speaker diagnosed with schizophrenia then participated in a hallucination simulation. Mental illness stigma was measured before and after the intervention using the Opening Minds Survey for Health Care Professionals (OMS-HC). Related-samples Wilcoxon-signed rank tests were used to evaluate changes in OMS-HC scores. An inductive qualitative analysis was conducted on student perceptions of patients with psychosis. OMS-HC total scores were reduced by an average of 2.0 ± 5.6 (P = .005) for the first-year pilot and 2.3 ± 7.0 (P < .001) for the subsequent year. OMS-HC attitudes (P = .005) and disclosure/help-seeking (P < .005) subscales decreased both years. There was no significant change in the social distance subscale (P = .205) the first year and a significant decrease (P = .015) the second year. The themes identified from the open-ended comments were increased awareness, sympathy, empathy, inspiration/admiration, discomfort, and change to patient care. The combination of a speaker with schizophrenia and auditory hallucination simulation effectively reduced mental illness stigma. The combination is likely effective for reducing stigmatizing attitudes and willingness to disclose mental illness with variable reduction in desired social distance.