Background: Infants with acute lymphoblastic leukemia (ALL) treated with high-dose methotrexate (MTX) may have reduced MTX clearance (CL) due to renal immaturity, which may predispose them to toxicity. The objective of this study was to develop a population pharmacokinetic (PK) model of MTX in infants with ALL.Methods: A total of 672 MTX plasma concentrations were obtained from 71 infants enrolled in the Children's Oncology Group (COG) Clinical Trial P9407. Infants received MTX 4 g/m 2 intravenously for four cycles during weeks 4-12 of intensification. A population PK analysis was performed using NONMEM® version 7.4. The final model was evaluated using a non-parametric bootstrap, a visual predictive check, and simulations were performed to evaluate MTX dosage and the utility of a bedside algorithm for dose individualization.Results: MTX was best characterized by a two-compartment model with allometric scaling. Weight was the only covariate included in the final model. The coefficient of variation for interoccasion variability (IOV) on CL was relatively high at 25.4%, compared to the

Objective. To design, implement, and assess the initial impact of a pharmacy student research and scholarship training pathway. Methods. The Research and Scholarship in Pharmacy (RASP) pathway was designed to create a longitudinal, elective pathway within a Doctor of Pharmacy (PharmD) curriculum at a single institution. The pathway consisted of three elective courses built around a faculty-mentored scholarly project where students framed an answerable question, generated and interpreted relevant data, and communicated their findings in oral and written form. Following implementation, a retrospective, multimethod analysis was conducted to evaluate the impact of the program on the initial two student cohorts that completed it and assess their perceptions of the value of the pathway. Results. Fifty students (25 in each of two cohorts) completed the three-course sequence. Students were supported by 33 distinct faculty mentors. Thirty-eight (76%) students presented an abstract derived from their project at a national meeting. The first cohort exit survey (96% response rate) revealed positive student perceptions regarding the value of and satisfaction with the research pathway. Twentythree (96%) students were satisfied with their research experience, 21 (88%) were satisfied with their faculty mentor, and 24 (100%) were satisfied with their development of project management skills. In the first cohort, 10 (40%) students published an original research manuscript within one year of graduation. Conclusion.The Research and Scholarship in Pharmacy pathway feasibly and effectively provided a mechanism for students to engage in a faculty-mentored longitudinal research experience within a PharmD curriculum that promoted skill development and opportunities for scholarship. Initial implementation demonstrated high rates of student satisfaction, low rates of student attrition, and high rates of scholarly output.

Fluconazole is an antifungal agent used for the treatment of invasive candidiasis, a leading cause of morbidity and mortality in premature infants. Population pharmacokinetic (PK) models of fluconazole in infants have been previously published by Wade et al. (Antimicrob Agents Chemother 52:4043-4049, 2008, https://doi.org/10.1128/AAC.00569-08) and Momper et al. (Antimicrob Agents Chemother 60:5539-5545, 2016, https://doi.org/10.1128/AAC.00963-16). Here we report the results of the first external evaluation of the predictive performance of both models. We used patient-level data from both studies to externally evaluate both PK models. The predictive performance of each model was evaluated using the model prediction error (PE), mean prediction error (MPE), mean absolute prediction error (MAPE), prediction-corrected visual predictive check (pcVPC), and normalized prediction distribution errors (NPDE). The values of the parameters of each model were reestimated using both the external and merged data sets. When evaluated with the external data set, the model proposed by Wade et al. showed lower median PE, MPE, and MAPE (0.429 μg/ml, 41.9%, and 57.6%, respectively) than the model proposed by Momper et al. (2.45 μg/ml, 188%, and 195%, respectively). The values of the majority of reestimated parameters were within 20% of their respective original parameter values for all model evaluations. Our analysis determined that though both models are robust, the model proposed by Wade et al. had greater accuracy and precision than the model proposed by Momper et al., likely because it was derived from a patient population with a wider age range. This study highlights the importance of the external evaluation of infant population PK models.

Hepatocellular carcinoma (HCC) is the second most common cause of cancer death worldwide. HCC tumor development and treatment resistance are impacted by changes in the microenvironment of the hepatic immune system. Immunotherapy has the potential to improve response rates by overcoming immune tolerance mechanisms and strengthening anti-tumor activity in the tumor microenvironment. In this review, we characterize the impact of immunotherapy on outcomes of advanced HCC, as well as the active clinical trials evaluating novel combination immunotherapy strategies. In particular, we discuss the efficacy of atezolizumab and bevacizumab as demonstrated in the IMbrave150 study, which created a new standard of care for the front-line treatment of advanced HCC. However, there are multiple ongoing trials that may present additional front-line treatment options depending on their efficacy/toxicity results. Furthermore, the preliminary data on the application of chimeric antigen receptor (CAR-T) cell therapy for treatment of HCC suggests this may be a promising option for the future of advanced HCC treatment.

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Objective. To improve the quality of admissions interviews for a doctor of pharmacy program, using a multiple mini-interview (MMI) in place of the standard interview. Methods. Stakeholders completed an anonymous web-based survey. This study characterized perceptions of the MMI format across 3 major stakeholders (candidates, interviewers, admissions committee members) and included comparative cost estimates. Costs were estimated using human and facility resources from the 2012 cycle (standard format) and the 2013 cycle (MMI format). Results. Most candidates (65%), interviewers (86%), and admissions committee members (79%) perceived the MMI format as effective for evaluating applicants, and most (59% of candidates, 84% of interviewers, 77% of committee members) agreed that the MMI format should be continued. Cost per candidate interviewed was $136.34 (standard interview) vs $75.30 (MMI). Conclusion. Perceptions of the MMI process were favorable across stakeholder groups, and this format was less costly per candidate interviewed.

Disclaimer In an effort to expedite the publication of articles related to the COVID-19 pandemic, AJHP is posting these manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. Purpose To describe the perceptions of residency candidates, residency practitioners (current residents and preceptors), and residency program directors (RPDs) regarding a virtual interview process for pharmacy residency programs across multiple institutions. Methods In May 2021, an anonymous web-based questionnaire characterizing perceptions of the virtual interview process used during the coronavirus disease 2019 (COVID-19) pandemic was distributed to residency candidates, residency practitioners, and RPDs across 13 institutions. Quantitative responses measured on a 5-point Likert scale were summarized with descriptive statistics, and open-ended questions were analyzed using thematic qualitative methods. Results 236 residency candidates and 253 residency practitioners/RPDs completed the questionnaire, yielding response rates of 27.8% (236 of 848), and 38.1% (253 of 663), respectively. Overall, both groups perceived the virtual interview format positively. When asked whether virtual interviews should replace in-person interviews moving forward, 60.0% (18 of 30) of RPDs indicated they agreed or strongly agreed, whereas only 30.5% (61 of 200) of current preceptors/residents and 28.7% (66 of 230) of residency candidates agreed or strongly agreed. Thematic analysis of qualitative responses revealed that while virtual interviews were easier logistically, the lack of in-person interactions was a common concern for many stakeholders. Lastly, the majority (65.0%) of residency candidates reported greater than $1,000 in savings with virtual interviews. Conclusion Virtual interviews offered logistical and financial benefits. The majority of RPDs were in favor of offering virtual interviews to replace in-person interviews, whereas the majority of residency candidates and practitioners preferred on-site interviews. As restrictions persist with the ongoing pandemic, our results provide insight into best practices for virtual pharmacy residency interviews.

Introduction Haemophilia A patients require perioperative clotting factor replacement to limit excessive bleeding. Weight‐based dosing of Factor VIII (FVIII) does not account for inter‐individual pharmacokinetic (PK) variability, and may lead to suboptimal FVIII exposure. Aim To perform an external validation of a previously developed population PK (popPK) model of perioperative FVIII in haemophilia A patients. Methods A retrospective chart review identified perioperative haemophilia A patients at the University of North Carolina (UNC) between April 2014 and November 2019. Patient data was used to externally validate a previously published popPK model proposed by Hazendonk. Based on these validation results, a modified popPK model was developed to characterize FVIII PK in our patients. Dosing simulations were performed using this model to compare FVIII target attainment between intermittent bolus (IB) and continuous infusion (CI) administration methods. Results A total of 521 FVIII concentrations, drawn from 34 patients, were analysed. Validation analyses revealed that the Hazendonk model did not fully capture FVIII PK in the UNC cohort. Therefore, a modified one‐compartment model, with weight and age as covariates on clearance (CL), was developed. Dosing simulations revealed that CI resulted in improved target attainment by 16%, with reduced overall FVIII usage by 58 IU/kg, compared to IB. Conclusion External validation revealed a previously published popPK model of FVIII did not adequately characterize UNC patients, likely due to differences in patient populations. Future prospective studies are needed to evaluate our model prior to implementation into clinical practice.