Liver injury from tumor necrosis factor-α antagonists: analysis of thirty-four cases.

BACKGROUND & AIMS: Tumor necrosis factor (TNF)-α antagonists have been associated with drug-induced liver injury (DILI). We reviewed cases of DILI in the United States to identify those associated with use of TNF-α antagonists. METHODS: We searched the U.S. DILI Network (DILIN) database, from 2003 to 2011, for cases associated with TNF-α antagonists. Mean Roussel-Uclaf Causality Assessment Method scores were calculated. A DILIN severity score was assigned according to a previously published scale, and we identified 6 subjects likely to have DILI associated with use of TNF-α antagonists. We also searched PubMed for articles that reported hepatotoxicity from TNF-α antagonists, identifying 28 additional cases suitable for analysis. RESULTS: The drugs presumed to have caused DILI were infliximab (n = 26), etanercept (n = 4), and adalimumab (n = 4). The anti-TNF-α agent was the probable cause of 12 cases of DILI (35%), a very likely cause for 21 (62%), and a definite cause for 1 (3%). Median latency was 13 weeks (range, 2-104); however, 7 cases (20%) had latency periods longer than 24 weeks. Twenty-two of 33 subjects who underwent serologic analysis (67%) tested positive for anti-nuclear and/or smooth muscle antibodies. Of these 22, 17 underwent liver biopsy; 15 subjects had clear features of autoimmunity. The 22 subjects with autoimmune features had longer median latency (16 vs 10 weeks) and higher peak levels of alanine aminotransferase (784 vs 528 U/L) than the 12 without such features. There was 1 case of severe cholestasis. All but one subject improved after discontinuation of the implicated drug; 12 subjects received corticosteroid therapy. No deaths were attributed to liver injury, although one patient with preexistent cirrhosis required liver transplantation. CONCLUSIONS: Acute liver injury caused by TNF-α antagonists may be a class effect because multiple agents in this category have been implicated. The most common presentation is an autoimmune phenotype with marked hepatocellular injury, but a mixed non-autoimmune pattern or predominant cholestasis also occurs. The prognosis is usually good after drug discontinuation, although some patients may benefit from a course of corticosteroids. ClinicalTrials.gov: Number, NCT00345930.

Social desirability bias in self-reported dietary, physical activity and weight concerns measures in 8- to 10-year-old African-American girls: results from the Girls Health Enrichment Multisite Studies (GEMS).

BACKGROUND: Social desirability (SocD) may bias children's self-reported health behaviors and attitudes and confound relationships with health outcome measures. METHODS: Ninety-five, 8- to 10-year-old African-American girls completed dietary recalls, a physical activity checklist, psychosocial questionnaires related to diet, and physical activity; and 3 days of physical activity monitoring. Potential SocD construct bias was investigated by comparing designated criterion measures of physical activity, beverage intake, and body mass index (BMI) with respective self-reported measures related to activity, beverage preferences, and body image and weight concerns in cross-sectional regression models. Potential confounding by SocD of associations between self-reported behaviors with BMI was assessed using change-in-coefficient regression analyses. RESULTS: Controlling for age and BMI, overestimates of self-reported activity (P = 0.02), underestimates of sweetened beverage preferences (P = 0.02), and lower ratings of weight concerns and dieting behaviors (P's < 0.05) were related to SocD. Confounding by SocD of associations between self-reported physical activity and energy intake with BMI was found. CONCLUSIONS: In 8- to 10-year-old African-American girls, SocD was found to bias self-reports of diet and physical activity and confound associations between BMI and self-reported physical activity and energy intake. Methods to measure and control SocD bias are needed to reduce potential distortion of relationships between diet and physical activity and health outcomes.

Psychometric properties of optimism and pessimism: results from the Girls' Health Enrichment Multisite Studies.

UNLABELLED: Background. This study investigated the relationships among optimism, pessimism, physical activity, and dietary behaviors among 8- to 10-year-old African-American girls in the Girls' Health Enrichment Multisite Studies (GEMS). Methods. Ninety-two girls were randomly assigned to a 12-week physical activity and diet intervention or comparison group and completed psychosocial assessments including the Youth Life Orientation Test (YLOT) of optimism and pessimism, physical performance self-concept, physical activity self-efficacy, physical activity outcome expectancies, and physical activity and sedentary preferences. Also, preferences for bottled water and sweetened beverages were assessed. Physical activity and dietary intake were assessed by self-report and parent-report at baseline and follow-up. Also, physical activity was objectively assessed by wearing an accelerometer for 3 days. The psychometric properties of the optimism-pessimism subscales were analyzed. Results. The measures of optimism and pessimism in children were reliable (r = 0.75-0.82). In the multiple regression analyses without the intervention interaction terms, pessimism was positively and significantly related to increases in MET-adjusted usual activity (P = 0.008) and sedentary behaviors (P = 0.0004). Additionally, a negative (P = 0.026) pessimism by intervention interaction term for MET-adjusted usual activity was found such that the intervention group had a lower change in physical activity per unit increase in pessimism compared to the control group. CONCLUSIONS: Among 8- to 10-year-old African-American girls, pessimism was related to increased sedentary behaviors and usual activity. Previous studies have reported relationships between optimism and health-compromising behaviors. This study found that pessimism may positively or negatively influence efforts to increase health-promoting behaviors. Future research should confirm and clarify the meaning of these findings.