Ravindra Arya1, Catherine W Gillespie2, Avital Cnaan2, Mahima Devarajan2, Peggy Clark2, Shlomo Shinnar2, Alexander A Vinks2, Kana Mizuno2, Tracy A Glauser2. 1. From the Comprehensive Epilepsy Center (R.A., M.D., P.C., T.A.G.), Division of Neurology, and Division of Clinical Pharmacology (A.A.V., K.M.), Cincinnati Children's Hospital Medical Center, Cincinnati, OH; Children's National Health System (C.W.G., A.C.), Washington, DC; and Montefiore Medical Center (S.S.), Albert Einstein College of Medicine, Bronx, NY. ravindra.arya@cchmc.org. 2. From the Comprehensive Epilepsy Center (R.A., M.D., P.C., T.A.G.), Division of Neurology, and Division of Clinical Pharmacology (A.A.V., K.M.), Cincinnati Children's Hospital Medical Center, Cincinnati, OH; Children's National Health System (C.W.G., A.C.), Washington, DC; and Montefiore Medical Center (S.S.), Albert Einstein College of Medicine, Bronx, NY.
Abstract
OBJECTIVE: This study examined whether overweight and obesity are pretreatment comorbidities and predictors of short-term drug response in newly diagnosed untreated childhood absence epilepsy (CAE). We also examined whether dietary intake accounts for observed pretreatment body mass index (BMI) distribution. METHODS: Pretreatment height and weight were available for 445 of 446 participants in the NIH-funded CAE comparative effectiveness trial (NCT00088452). Twenty-four-hour dietary recalls were collected. Calculated BMI and dietary intake were standardized for age, sex, and race/ethnicity and compared to age-matched US population from the National Health and Nutrition Examination Survey (NHANES). Logistic regression models tested BMI as a predictor of treatment response. Pharmacokinetic variables were explored as contributors to differential drug response. RESULTS: After standardizing for demographic differences, children with CAE were more likely to be overweight (19.3% vs 13.8%; p < 0.001) or obese (14.5% vs 11.5%; p < 0.001) than NHANES controls. The combined prevalence of overweight and obesity was 33.8% in the CAE cohort and 25.3% among controls (p < 0.001). Mean daily energy intake (difference -79.5 kcal/day, p = 0.04) and daily carbohydrate intake (difference -10.7 g/day, p = 0.04) were lower in the CAE group than in NHANES controls. With increasing baseline BMI z score, the efficacy and effectiveness of ethosuximide and valproic acid over lamotrigine became more pronounced, despite no significant differences in drug exposure and trough levels. CONCLUSIONS: Overweight and obesity are more prevalent in children with newly diagnosed CAE than in age-matched peers, despite lower caloric and carbohydrate intake. Baseline BMI may also predict differential drug response, which cannot be attributed to pharmacokinetic differences.
OBJECTIVE: This study examined whether overweight and obesity are pretreatment comorbidities and predictors of short-term drug response in newly diagnosed untreated childhood absence epilepsy (CAE). We also examined whether dietary intake accounts for observed pretreatment body mass index (BMI) distribution. METHODS: Pretreatment height and weight were available for 445 of 446 participants in the NIH-funded CAE comparative effectiveness trial (NCT00088452). Twenty-four-hour dietary recalls were collected. Calculated BMI and dietary intake were standardized for age, sex, and race/ethnicity and compared to age-matched US population from the National Health and Nutrition Examination Survey (NHANES). Logistic regression models tested BMI as a predictor of treatment response. Pharmacokinetic variables were explored as contributors to differential drug response. RESULTS: After standardizing for demographic differences, children with CAE were more likely to be overweight (19.3% vs 13.8%; p < 0.001) or obese (14.5% vs 11.5%; p < 0.001) than NHANES controls. The combined prevalence of overweight and obesity was 33.8% in the CAE cohort and 25.3% among controls (p < 0.001). Mean daily energy intake (difference -79.5 kcal/day, p = 0.04) and daily carbohydrate intake (difference -10.7 g/day, p = 0.04) were lower in the CAE group than in NHANES controls. With increasing baseline BMI z score, the efficacy and effectiveness of ethosuximide and valproic acid over lamotrigine became more pronounced, despite no significant differences in drug exposure and trough levels. CONCLUSIONS: Overweight and obesity are more prevalent in children with newly diagnosed CAE than in age-matched peers, despite lower caloric and carbohydrate intake. Baseline BMI may also predict differential drug response, which cannot be attributed to pharmacokinetic differences.
Authors: Tracy A Glauser; Avital Cnaan; Shlomo Shinnar; Deborah G Hirtz; Dennis Dlugos; David Masur; Peggy O Clark; Peter C Adamson Journal: Epilepsia Date: 2012-11-21 Impact factor: 5.864
Authors: Tracy A Glauser; Avital Cnaan; Shlomo Shinnar; Deborah G Hirtz; Dennis Dlugos; David Masur; Peggy O Clark; Edmund V Capparelli; Peter C Adamson Journal: N Engl J Med Date: 2010-03-04 Impact factor: 91.245
Authors: Mary Jo V Pugh; Janice E Knoefel; Eric M Mortensen; Megan E Amuan; Dan R Berlowitz; Anne C Van Cott Journal: J Am Geriatr Soc Date: 2009-02 Impact factor: 5.562
Authors: Vanessa Zen; Flávio D Fuchs; Marco V Wainstein; Sandro C Gonçalves; Karina Biavatti; Charles E Riedner; Felipe C Fuchs; Rodrigo V Wainstein; Ernani L Rhoden; Jorge P Ribeiro; Sandra C Fuchs Journal: Am J Cardiovasc Dis Date: 2012-10-25