Rice, Mikhaila

Background: A summary of pharmacist-based practices and preferences regarding the prevention and management of high-dose methotrexate (HDMTX) toxicity in patients with lymphoma does not exist. The objective of the study was to describe current practices surrounding management of HDMTX therapy. This was done through a self-administered, web-based, cross-sectional survey of hematology/oncology pharmacists to ascertain practices and individual attitudes about HDMTX therapy management. Responses were summarized with descriptive statistics. Response comparisons were made using Chi-square or Fisher’s exact test for categorical data, and Kruskal-Wallis test for variables on the Likert scale. A total of 175 pharmacists provided 116 eligible surveys [68 (59%) complete responses and 48 (41%) partial responses] for analysis. The Cockcroft-Gault estimated creatinine clearance formula was the most preferred method (61%) to estimate kidney function and determine HDMTX dosing. Respondents would proceed with HDMTX therapy until the predicted risk of AKI, or AKI stage 2 or 3, exceeded 50% and 20%, respectively. Preferred treatment modifications for a high predicted AKI risk after HDMTX exposure included additional prehydration, HDMTX dose reduction, and increased kidney function monitoring, although levels and degrees of agreement varied. Respondents indicated that serum cystatin C-based GFR estimates lacked evidence, accuracy, and practicality in HDMTX therapy management. There was limited familiarity with cell cycle arrest biomarker use during HDMTX therapy. Glucarpidase was considered time-sensitive and highly effective; however, acquisition cost represented a barrier to use, and the optimal dose was felt to be unknown. In conclusion, there is significant heterogeneity in supportive practices and beliefs about the optimal management for patients with lymphoma receiving HDMTX therapy.

AbstractStudy ObjectiveTo develop and validate a model for predicting acute kidney injury (AKI) after high‐dose methotrexate (HDMTX) exposure.DesignRetrospective analysis.SettingMultisite integrated health system throughout Minnesota and Wisconsin.PatientsAdult patients with lymphoma who received HDMTX as a 4‐h infusion.Measurements and Main ResultsLASSO methodology was used to identify factors available at the outset of therapy that predicted incident AKI within 7 days following HDMTX. The model was then validated in an independent cohort. The incidence of AKI within 7 days following HDMTX was 21.6% (95% confidence interval (CI) 18.4%‐24.8%) in the derivation cohort (435 unique patients who received a total of 1642 doses of HDMTX) and 15.6% (95% CI 5.3%‐24.8%) in the validation cohort (55 unique patients who received a total of 247 doses of HDMTX). Factors significantly associated with AKI after HDMTX in the multivariable model included age ≥ 55 years, male sex, and lower HDMTX dose number. Other factors that were not found to be significantly associated with AKI on multivariable analysis, but were included in the final model, were body surface area, Charlson Comorbidity Index, and estimated glomerular filtration rate. The c‐statistic of the model was 0.72 (95% CI 0.69‐0.75) in the derivation cohort and 0.72 (95% CI 0.60‐0.84) in the validation cohort.ConclusionThis model utilizing identified sociodemographic and clinical factors is predictive of AKI following HDMTX administration in adult patients with lymphoma.

AbstractBackgroundPneumocystis jirovecii pneumonia (PJP) is a life‐threatening infection occurring in patients receiving bendamustine. The poorly defined incidence, particularly when utilizing polymerase chain reaction (PCR)‐based diagnostic techniques, precipitates unclear prophylaxis recommendations. Our objective was to determine the cumulative incidence of PJP diagnosed by single copy target, non‐nested PCR in patients receiving bendamustine.MethodsPatients were evaluated for PJP from initiation of bendamustine through 9 months after the last administration. The cumulative incidence of PJP was estimated using the Aalen–Johansen method. Cox proportional hazard models were used to demonstrate the strength of association between the independent variables and PJP risk.ResultsThis single‐center, retrospective cohort included 486 adult patients receiving bendamustine from 1 January 2006 through 1 August 2019. Most patients received bendamustine‐based combination therapy (n = 461, 94.9%), and 225 (46.3%) patients completed six cycles. Rituximab was the most common concurrent agent (n = 431, 88.7%). The cumulative incidence of PJP was 1.7% (95% CI 0.8%–3.3%, at maximum follow‐up of 2.5 years), after the start of bendamustine (n = 8 PJP events overall). Prior stem cell transplant, prior chemotherapy within 1 year of bendamustine, and lack of concurrent chemotherapy were associated with the development of PJP in univariate analyses. Anti‐Pneumocystis prophylaxis was not significantly associated with a reduction in PJP compared to no prophylaxis (HR 0.37, 95% CI (0.05, 3.04), p = 0.36).ConclusionsOur incidence of PJP below 3.5%, the conventional threshold for prophylaxis implementation, indicates routine anti‐Pneumocystis prophylaxis may not be necessary in this population. Factors indicating a high‐risk population for targeted prophylaxis require further investigation.

Abstract Purpose Letters of recommendation (LORs) are highly regarded components of pharmacy residency applications, as they provide insight into an applicant’s character and capabilities. In other medical fields, differences in language have been reported for letters written for female and male applicants; however, data on gender differences in LORs for pharmacy residency applications are currently lacking. Methods LORs for applicants to our institution’s postgraduate year 1 pharmacy residency program for the 2019-2020 academic year were extracted and processed by a natural language processing service. Words within 18 categories were identified and counted for each LOR. Total word count was also compared. Results Of the 473 LORs included for analysis, 320 (67.7%) were written for female applicants and 153 (32.3%) were written for male applicants. Approximately two-thirds of all writers were women for both female and male applicants. In comparing letters for women and men, there was a statistically significant difference in the percentage of LORs that contained terms in categories described as gendered, solitary/reserved, and desire. There was no statistically significant difference in total word count or in the presence of words in other categories such as grindstone, standout, agentic, or communal. When controlling for grade point average, writer gender, duration that the writer knew the applicant, and the writer’s professional position, there were no changes to the statistical findings. Conclusion Letters written for female and male applicants were largely similar with regard to length and word categories utilized. While no clear gender bias was found when evaluating pharmacy residency LORs, writers must continue to assess their implicit biases and how those biases might affect a candidate’s application.