ABSTRACT
IMPORTANCE: Protein binding of valproate varies among ICU patients, altering the biologically active free valproate concentration (VPAC). Free VPAC is measured at few laboratories and is often discordant with total VPAC. Existing equations to predict free VPAC are either not validated or are inaccurate in ICU patients. OBJECTIVES: We designed this study to derive and validate a novel equation to predict free VPAC using data from ICU patients and to compare its performance to published equations. DESIGN: Retrospective cohort study. SETTING: Two academic medical centers. PARTICIPANTS: Patients older than 18 years old with concomitant free and total VPACs measured in the ICU were included in the derivation cohort if admitted from 2014 to 2018, and the validation cohort if admitted from 2019 to 2022. MAIN OUTCOMES AND MEASURES: Multivariable linear regression was used to derive an equation to predict free VPAC. Modified Bland-Altman plots and the rate of therapeutic concordance between the measured and predicted free VPAC were compared. RESULTS: Demographics, median free and total VPACs, and valproate free fractions were similar among 115 patients in the derivation cohort and 147 patients in the validation cohort. The Bland-Altman plots showed the new equation performed better (bias, 0.3 [95% limits of agreement, -13.6 to 14.2]) than the Nasreddine (-9.2 [-26.5 to 8.2]), Kodama (-9.7 [-30.0 to 10.7]), Conde Giner (-7.9 [-24.9 to 9.1]), and Parent (-9.9 [-30.7 to 11.0]) equations, and similar to Doré (-2.0 [-16.0 to 11.9]). The Doré and new equations had the highest therapeutic concordance rate (73%). CONCLUSIONS AND RELEVANCE: For patients at risk of altered protein binding such as ICU patients, existing equations to predict free VPAC are discordant with measured free VPAC. A new equation had low bias but was imprecise. External validation should be performed to improve its precision and generalizability. Until then, monitoring free valproate is recommended during critical illness.
ABSTRACT
Objective. To examine the placement of pathophysiology, anatomy, and physiology within the curricula of US pharmacy schools and colleges for variations in program length, prerequisites, institution type, geographic region, and establishment date.Methods. The websites of 146 pharmacy programs were examined for information related to pathophysiology, anatomy, and physiology courses and instruction. Eight programs listed uninterpretable or incomplete website data and were excluded, producing a final sample size of 138 programs. Data were analyzed to determine differences in curricular placement, credit hours, and integration.Results. The majority (65.3%) of pathophysiology courses were incorporated into the curriculum by integration, while some (14.5%) had both stand-alone and integrated pathophysiology courses. The remaining programs (20.2%) had stand-alone pathophysiology courses only. Of those with stand-alone pathophysiology courses, the mean number of credit hours was 5. Most programs (76.1%) required anatomy and/or physiology as a prerequisite or as part of the professional program, with significantly more public programs than private programs requiring it as a prerequisite (77.9% vs 48.6%).Conclusion. Pathophysiology is taught in diverse formats throughout US pharmacy schools, with the only consensus among programs being that it belongs in the professional curriculum. While the majority of programs teach pathophysiology as an integrated course, stand-alone courses are also common. There is also great diversity in the type of instruction used in anatomy and physiology courses. While every program requires students to complete anatomy and physiology courses, these are commonly taught as part of the professional curriculum or are prerequisites. Overall, there are few significant differences in the instruction of these subjects among US pharmacy schools.
