Drugs in Human Milk Part 1: Practical and Analytical Considerations in Measuring Drugs and Metabolites in Human Milk.

Human milk is a remarkable biofluid that provides essential nutrients and immune protection to newborns. Breastfeeding women consuming medications could pass the drug through their milk to neonates. Drugs can be transferred to human milk by passive diffusion or active transport. The physicochemical properties of the drug largely impact the extent of drug transfer into human milk. A comprehensive understanding of the physiology of human milk formation, composition of milk, mechanisms of drug transfer, and factors influencing drug transfer into human milk is critical for appropriate selection and use of medications in lactating women. Quantification of drugs in the milk is essential for assessing the safety of pharmacotherapy during lactation. This can be achieved by developing specific, sensitive, and reproducible analytical methods using techniques such as liquid chromatography coupled with mass spectrometry. The present review briefly discusses the physiology of human milk formation, composition of human milk, mechanisms of drug transfer into human milk, and factors influencing transfer of drugs from blood to milk. We further expand upon and critically evaluate the existing analytical approaches/assays used for the quantification of drugs in human milk.

Trends in endpoint use in pivotal trials and efficacy for US Food and Drug Administration-approved solid tumor therapies, 1995-2021.

BACKGROUND: Many cancer therapies are now approved based on surrogate endpoints such as progression-free survival (PFS) to ensure that patients have speedy access to life-saving cancer medicines. However, the link between surrogate endpoints and overall survival (OS) is not well established in many cancers. OBJECTIVE: To characterize trends in endpoints used in pivotal trials leading to approval for US Food and Drug Administration (FDA)-approved solid tumor therapies and their efficacy from 1995 to 2021. METHODS: We reviewed the FDA Oncology (Cancer)/Hematologic Malignancies Approval Notifications webpage to extract data on median OS and PFS among solid tumor therapy approvals from 1995 to 2021. We summarized trends in percentage of trials reporting OS vs PFS, median OS and PFS, and trial designs. We conducted subgroup analyses for lung and breast cancer therapies. RESULTS: Median OS was reported more frequently until 2010 to 2012, when median PFS and OS were reported in 65.2% and 60.9% of trials, respectively. Between 1995 and 2021, there were no observable trends in median OS over time for solid tumor therapy approvals. Median PFS increased by 3.0 months over time. For lung cancer therapies, median OS increased by 6.8 months between the time periods of 1998-2000 and 2019-2021, whereas median PFS increased by 5.0 months between the time periods of 2007-2009 and 2019-2021. For breast cancer therapy, median OS slightly decreased over time, whereas median PFS has increased by 3.4 months since 1995. There has been a recent shift in use of single-arm trials leading to oncology drug approvals. CONCLUSIONS: There has been a transition from reporting OS to PFS, and median PFS has increased by 3 months while median OS has remained stable. The different trends in overall and progression-free survival highlights the challenge and importance of measuring the value of oncology drugs. DISCLOSURES: Dr Suh reports personal fees from Bayer US LLC.

Veterans with PTSD and comorbid substance use disorders: Does single versus poly-substance use disorder affect treatment outcomes?

INTRODUCTION: Substance use disorders (SUD) frequently co-occur with posttraumatic stress disorder (PTSD). Little is known, however, about how individuals with a single SUD diagnosis (relating to only one substance) compare to individuals with poly-SUD diagnoses (relating to more than one substance) on substance use and PTSD treatment outcomes. To address this gap in the literature, we utilized data from a larger study investigating a 12-week integrated, exposure-based treatment (i.e., Concurrent Treatment of PTSD and Substance Use Disorders using Prolonged Exposure, or COPE) to examine treatment outcomes by single vs. poly-SUD status. METHOD: Participants were 54 Veterans (92.6% male, average age = 39.72) categorized as having single SUD (n = 39) or poly-SUD (n = 15). T-tests characterized group differences in baseline demographics and presenting symptomatology. Multilevel models examined differences in treatment trajectories between participants with single vs. poly-SUD. RESULTS: Groups did not differ on baseline frequency of substance use, PTSD symptoms, or treatment retention; however, individuals with poly-SUD evidenced greater reductions in percent days using substances than individuals with a single SUD, and individuals with a single SUD had greater reductions in PTSD symptoms than individuals with poly-SUD over the course of treatment. DISCUSSION: The findings from this exploratory study suggest that Veterans with PTSD and co-occurring poly-SUD, as compared to a single-SUD, may experience greater improvement in substance use but less improvement in PTSD symptoms during integrated treatment. Future research should identify ways to enhance treatment outcomes for individuals with poly-SUD, and to better understand mechanisms of change for this population.