Browsing by Author "Franciosi, James P."

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    Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2C19 and Proton Pump Inhibitor Dosing
    (Wiley, 2021) Lima, John J.; Thomas, Cameron D.; Barbarino, Julia; Desta, Zeruesenay; Van Driest, Sara L.; El Rouby, Nihal; Johnson, Julie A.; Cavallari, Larisa H.; Shakhnovich, Valentina; Thacker, David L.; Scott, Stuart A.; Schwab, Matthias; Uppugunduri, Chakradhara Rao S.; Formea, Christine M.; Franciosi, James P.; Sangkuhl, Katrin; Gaedigk, Andrea; Klein, Teri E.; Gammal, Roseann S.; Furuta, Takahisa; Medicine, School of Medicine
    Proton pump inhibitors (PPIs) are widely used for acid suppression in the treatment and prevention of many conditions, including gastroesophageal reflux disease, gastric and duodenal ulcers, erosive esophagitis, Helicobacter pylori infection, and pathological hypersecretory conditions. Most PPIs are metabolized primarily by cytochrome P450 2C19 (CYP2C19) into inactive metabolites, and CYP2C19 genotype has been linked to PPI exposure, efficacy, and adverse effects. We summarize the evidence from the literature and provide therapeutic recommendations for PPI prescribing based on CYP2C19 genotype (updates at www.cpicpgx.org). The potential benefits of using CYP2C19 genotype data to guide PPI therapy include (i) identifying patients with genotypes predictive of lower plasma exposure and prescribing them a higher dose that will increase the likelihood of efficacy, and (ii) identifying patients on chronic therapy with genotypes predictive of higher plasma exposure and prescribing them a decreased dose to minimize the risk of toxicity that is associated with long-term PPI use, particularly at higher plasma concentrations.
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    PedsQL™ Eosinophilic Esophagitis Module: Feasibility, Reliability and Validity
    (Wiley, 2013) Franciosi, James P.; Hommel, Kevin A.; Bendo, Cristiane B.; King, Eileen C.; Collins, Margaret H.; Eby, Michael D.; Marsolo, Keith; Abonia, J. Pablo; von Tiehl, Karl F.; Putnam, Philip E.; Greenler, Alexandria J.; Greenberg, Allison B.; Bryson, Ronald A.; Davis, Carla M.; Olive, Anthony P.; Gupta, Sandeep K.; Erwin, Elizabeth A.; Klinnert, Mary D.; Spergel, Jonathan M.; Denham, Jolanda M.; Furuta, Glenn T.; Rothenberg, Marc E.; Varni, James W.; Pediatrics, School of Medicine
    Objective: Eosinophilic esophagitis (EoE) is a chronic esophageal inflammatory condition with a paucity of information on health-related quality of life (HRQOL). The objective of the study was to report on the measurement properties of the PedsQL EoE Module. Methods: The PedsQL EoE Module was completed in a multisite study by 196 pediatric patients with EoE and 262 parents of patients with EoE. Results: The PedsQL EoE Module scales evidenced excellent feasibility (0.6%-3.1% missing), excellent group comparison reliability across total scale scores (patient α 0.93; parent proxy α 0.94), good reliability for the 7 individual scales (patient α 0.75-0.87; parent proxy α 0.81-0.92), excellent test-retest reliability (patient intraclass correlation coefficient 0.88; parent intraclass correlation coefficient 0.82), demonstrated no floor effects and low ceiling effects, and demonstrated a high percentage of scaling success for most scales. Intercorrelations with the PedsQL Generic Core Scales were in the medium (0.30) to large (0.50) range. PedsQL EoE Module scores were worse among patients with active histologic disease (≥ 5 eos/hpf) compared with those in remission (patient self-report: 63.3 vs 69.9 [P < 0.05]; parent proxy report: 65.1 vs 72.3 [P < 0.01]), and those treated with dietary restrictions compared with those with no restrictions (patient self-report: 61.6 vs 74.3 [P < 0.01]; parent proxy report: 65.5 vs 74.7 [P < 0.01]). Conclusions: The results demonstrate excellent measurement properties of the PedsQL EoE Module. Patients with active histologic disease and those treated with dietary restrictions demonstrated worse PedsQL scores. The PedsQL EoE Module may be used in the evaluation of pediatric EoE disease-specific HRQOL in clinical research and practice.
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    Proton Pump Inhibitor Therapy for Eosinophilic Esophagitis: History, Mechanisms, Efficacy, and Future Directions
    (Dovepress, 2022-02-26) Franciosi, James P.; Mougey, Edward B.; Dellon, Evan S.; Gutierrez-Junquera, Carolina; Fernandez-Fernandez, Sonia; Venkatesh, Rajitha D.; Gupta, Sandeep K.; Pediatrics, School of Medicine
    Over the past decade, the role of proton pump inhibitor (PPI) medication has evolved from a diagnostic tool for Eosinophilic Esophagitis (EoE), by excluding patients with PPI responsive esophageal eosinophilia (PPI-REE), to a therapy for EoE. This transition resulted from the Updated International Consensus Diagnostic Criteria for Eosinophilic Esophagitis: Proceedings of the Appraisal of Guidelines for Research and Evaluation II (AGREE) Conference to support PPI therapy for EoE in children and adults. Additional recent advances have suggested a role for genetic variations that might impact response to PPI therapy for EoE. This review article will explore a brief background of EoE, the evolution of PPI therapy for EoE and its proposed mechanisms, efficacy and safety in children and adults, and considerations for future PPI precision medicine in patients with EoE.