- Browse by Author
Browsing by Author "Goldberg, David"
Now showing 1 - 2 of 2
Results Per Page
Sort Options
Item Height Versus Body Surface Area to Normalize Cardiovascular Measurements in Children Using the Pediatric Heart Network Echocardiographic Z-Score Database(Springer, 2021) Mahgerefteh, Joseph; Lai, Wyman; Colan, Steven; Trachtenberg, Felicia; Gongwer, Russel; Stylianou, Mario; Bhat, Aarti H.; Goldberg, David; McCrindle, Brian; Frommelt, Peter; Sachdeva, Ritu; Shuplock, Jacqueline Marie; Spurney, Christopher; Troung, Dongngan; Cnota, James F.; Camarda, Joseph A.; Levine, Jami; Pignatelli, Ricardo; Altmann, Karen; van der Velde, Mary; Thankavel, Poonam Punjwani; Chowdhury, Shahryar; Srivastava, Shubhika; Johnson, Tiffanie R.; Lopez, Leo; Pediatric Heart Network Investigators; Pediatrics, School of MedicineNormalizing cardiovascular measurements for body size allows for comparison among children of different ages and for distinguishing pathologic changes from normal physiologic growth. Because of growing interest to use height for normalization, the aim of this study was to develop height-based normalization models and compare them to body surface area (BSA)-based normalization for aortic and left ventricular (LV) measurements. The study population consisted of healthy, non-obese children between 2 and 18 years of age enrolled in the Pediatric Heart Network Echo Z-Score Project. The echocardiographic study parameters included proximal aortic diameters at 3 locations, LV end-diastolic volume, and LV mass. Using the statistical methodology described in the original project, Z-scores based on height and BSA were determined for the study parameters and tested for any clinically significant relationships with age, sex, race, ethnicity, and body mass index (BMI). Normalization models based on height versus BSA were compared among underweight, normal weight, and overweight (but not obese) children in the study population. Z-scores based on height and BSA were calculated for the 5 study parameters and revealed no clinically significant relationships with age, sex, race, and ethnicity. Normalization based on height resulted in lower Z-scores in the underweight group compared to the overweight group, whereas normalization based on BSA resulted in higher Z-scores in the underweight group compared to the overweight group. In other words, increasing BMI had an opposite effect on height-based Z-scores compared to BSA-based Z-scores. Allometric normalization based on height and BSA for aortic and LV sizes is feasible. However, height-based normalization results in higher cardiovascular Z-scores in heavier children, and BSA-based normalization results in higher cardiovascular Z-scores in lighter children. Further studies are needed to assess the performance of these approaches in obese children with or without cardiac disease.Item A randomized, placebo-controlled, phase II study of obeticholic acid for primary sclerosing cholangitis(Elsevier, 2020-07) Kowdley, Kris V.; Vuppalanchi, Raj; Levy, Cynthia; Floreani, Annarosa; Andreone, Pietro; LaRusso, Nicholas F.; Shrestha, Roshan; Trotter, James; Goldberg, David; Rushbrook, Simon; Hirschfield, Gideon M.; Schiano, Thomas; Jin, Yuying; Pencek, Richard; MacCone, Leigh; Shapiro, David; Bowlus, Christopher L.; Medicine, School of MedicineBackground & aims: Primary sclerosing cholangitis (PSC) is a rare, cholestatic liver disease with no currently approved therapies. Obeticholic acid (OCA) is a potent farnesoid X receptor (FXR) agonist approved for the treatment of primary biliary cholangitis. We investigated the efficacy and safety of OCA in patients with PSC. Methods: AESOP was a phase II, randomized, double-blind, placebo-controlled, dose-finding study. Eligible patients were 18 to 75 years of age with a diagnosis of PSC and serum alkaline phosphatase (ALP) ≥2× the upper limit of normal (ULN) and total bilirubin <2.5× ULN. Patients were randomized 1:1:1 to receive placebo, OCA 1.5-3.0 mg, or OCA 5-10 mg once daily for a 24-week, double-blind phase followed by a 2-year, long-term safety extension (LTSE). Primary endpoints were change in ALP from baseline to week 24, and safety. Results: The intent-to-treat population comprised 76 patients randomized to placebo (n = 25), OCA 1.5-3.0 mg (n = 25), and OCA 5-10 mg (n = 26). At week 24, serum ALP was significantly reduced with OCA 5-10 mg vs. placebo (least-square [LS] mean difference = -83.4 [SE = 40.3] U/L; 95% CI -164.28 to -2.57; p = 0.043). Serum ALP was not significantly reduced with OCA 1.5-3.0 mg vs. placebo at week 24 (LS mean [SE] difference = -78.29 [41.81] U/L; 95% CI -162.08 to 5.50; p = 0.067). Total bilirubin remained comparable to baseline in all groups. The most common treatment-emergent adverse event was dose-related pruritus (placebo 46%; OCA 1.5-3.0 mg 60%; OCA 5-10 mg 67%). Reductions in ALP were maintained during the LTSE, and no new safety signals emerged. Conclusions: Treatment with OCA 5-10 mg reduced serum ALP in patients with PSC. Mild to moderate dose-related pruritus was the most common adverse event.