Browsing by Author "Costantine, Maged M."

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    Performance of a Multianalyte 'Rule-Out' Assay in Pregnant Individuals With Suspected Preeclampsia
    (Wolters Kluwer, 2022) Costantine, Maged M.; Sibai, Baha; Bombard, Allan T.; Sarno, Mark; West, Holly; Haas, David M.; Tita, Alan T.; Paidas, Michael J.; Clark, Erin A. S.; Boggess, Kim; Grotegut, Chad; Grobman, William; Su, Emily J.; Burd, Irina; Saade, George; Chavez, Martin R.; Paglia, Michael J.; Merriam, Audrey; Torres, Carlos; Habli, Mounira; Macones, Georges; Wen, Tony; Bofill, James; Palatnik, Anna; Edwards, Rodney K.; Haeri, Sina; Oberoi, Pankaj; Mazloom, Amin; Cooper, Matthew; Lockton, Steven; Hankins, Gary D.; Obstetrics and Gynecology, School of Medicine
    Background: The ability to diagnose preeclampsia clinically is suboptimal. Our objective was to validate a novel multianalyte assay and characterize its performance, when intended for use as an aid to rule-out preeclampsia. Methods: Prospective, multicenter cohort study of pregnant individuals presenting between 280/7 and 366/7 weeks' with preeclampsia-associated signs and symptoms. Individuals not diagnosed with preeclampsia after baseline evaluation were enrolled in the study cohort, with those who later developed preeclampsia, classified as cases and compared with a negative control group who did not develop preeclampsia. Individuals with assay values at time of enrollment ≥0.0325, determined using a previously developed algorithm, considered at risk. The primary analysis was the time to develop preeclampsia assessed using a multivariate Cox regression model. Results: One thousand thirty-six pregnant individuals were enrolled in the study cohort with an incidence of preeclampsia of 30.3% (27.6%-33.2%). The time to develop preeclampsia was shorter for those with an at-risk compared with negative assay result (log-rank P<0.0001; adjusted hazard ratio of 4.81 [3.69-6.27, P<0.0001]). The performance metrics for the assay to rule-out preeclampsia within 7 days of enrollment showed a sensitivity 76.4% (67.5%-83.5%), negative predictive value 95.0% (92.8%-96.6%), and negative likelihood ratio 0.46 (0.32-0.65). Assay performance improved if delivery occurred <37 weeks and for individuals enrolled between 28 and 35 weeks. Conclusions: We confirmed that a novel multianalyte assay was associated with the time to develop preeclampsia and has a moderate sensitivity and negative likelihood ratio but high negative predictive value when assessed as an aid to rule out preeclampsia within 7 days of enrollment.
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    The MPRINT Hub Data, Model, Knowledge and Research Coordination Center: Bridging the gap in maternal-pediatric therapeutics research through data integration and pharmacometrics
    (Wiley, 2023) Quinney, Sara K.; Bies, Robert R.; Grannis, Shaun J.; Bartlett, Christopher W.; Mendonca, Eneida; Rogerson, Colin M.; Backes, Carl H.; Shah, Dhaval K.; Tillman, Emma M.; Costantine, Maged M.; Aruldhas, Blessed W.; Allam, Reva; Grant, Amelia; Abbasi, Mohammed Yaseen; Kandasamy, Murugesh; Zang, Yong; Wang, Lei; Shendre, Aditi; Li, Lang; Obstetrics and Gynecology, School of Medicine
    Maternal and pediatric populations have historically been considered "therapeutic orphans" due to their limited inclusion in clinical trials. Physiologic changes during pregnancy and lactation and growth and maturation of children alter pharmacokinetics (PK) and pharmacodynamics (PD) of drugs. Precision therapy in these populations requires knowledge of these effects. Efforts to enhance maternal and pediatric participation in clinical studies have increased over the past few decades. However, studies supporting precision therapeutics in these populations are often small and, in isolation, may have limited impact. Integration of data from various studies, for example through physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) modeling or bioinformatics approaches, can augment the value of data from these studies, and help identify gaps in understanding. To catalyze research in maternal and pediatric precision therapeutics, the Obstetric and Pediatric Pharmacology and Therapeutics Branch of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) established the Maternal and Pediatric Precision in Therapeutics (MPRINT) Hub. Herein, we provide an overview of the status of maternal-pediatric therapeutics research and introduce the Indiana University-Ohio State University MPRINT Hub Data, Model, Knowledge and Research Coordination Center (DMKRCC), which aims to facilitate research in maternal and pediatric precision therapeutics through the integration and assessment of existing knowledge, supporting pharmacometrics and clinical trials design, development of new real-world evidence resources, educational initiatives, and building collaborations among public and private partners, including other NICHD-funded networks. By fostering use of existing data and resources, the DMKRCC will identify critical gaps in knowledge and support efforts to overcome these gaps to enhance maternal-pediatric precision therapeutics.