Therapeutic challenges in two adolescent male patients with Fabry disease and high antibody titres.

Enzyme replacement therapy (ERT) has been shown to stabilize certain aspects of Fabry disease (FD). However, in some patients on ERT, high antibody titres have been documented, with limited clinical improvement in systemic manifestations and often with significant adverse drug reactions. We present two related adolescent males with a 4.5 kb GLA deletion, not amenable to chaperone therapy, leading to profound reduction in α-galactosidase A (α-gal A) enzyme activity. Over a 3-year period of ERT, increasing IgG antibody titres against α-gal A were noted. After starting ERT serial urine globotriaosylceramide (Gb3) measurements showed an upward trend from 333 to 2260 µg/mmol creatinine for patient 1 and 1165 to 2260 µg/mmol creatinine for patient 2. Markedly increased levels of urine and plasma globotriaosylsphingosine (Lyso-Gb3) analogues were also found. The patients experienced recurrent infusion-associated reactions necessitating premedication and prolonged infusion times. Over the 3-year period of ERT, the patients experienced continued malaise, gastrointestinal symptoms and neuropathic pain. In addition, they had increasing anxiety related to their disease and apparent lack of response to ERT which led to a decision to ultimately stop ERT. No other approved treatment options are currently available for these patients. It is possible that the rapid development of the high antidrug neutralizing antibody (ADA) titres is related to the large GLA deletion leading to virtually absent enzyme activity. It remains unclear if their symptomatology during the period of receiving ERT is related to lack of its efficacy, the rising ADA titres, or both. These two patients highlight the need for further research into the management of antidrug antibodies and additional therapeutic approaches for FD. SYNOPSIS: The development of very high antidrug antibody titres in response to ERT in two related adolescent males with FD highlight the need for other therapeutic options for patients in whom ERT or other currently approved therapies does not meet their treatment needs.

Impact of an online healthful eating and physical activity program for college students.

PURPOSE: To identify impact of an online nutrition and physical activity program for college students. DESIGN: Randomized, controlled trial using online questionnaires and on-site physical and fitness assessments with measurement intervals of 0 (baseline), 3 (postintervention), and 15 months (follow-up). SETTING: Online intervention delivered to college students; a centralized Web site was used for recruitment, data collection, data management, and intervention delivery. SUBJECTS: College students (18-24 years old, n = 1689), from eight universities (Michigan State University, South Dakota State University, Syracuse University, The Pennsylvania State University, Tuskegee University, University of Rhode Island, University of Maine, and University of Wisconsin). INTERVENTION: A 10-lesson curriculum focusing on healthful eating and physical activity, stressing nondieting principles such as size acceptance and eating competence (software developer: Rainstorm, Inc, Orono, Maine). MEASURES: Measurements included anthropometrics, cardiorespiratory fitness, fruit/vegetable (FV) intake, eating competence, physical activity, and psychosocial stress. ANALYSIS: Repeated measures analysis of variance for outcome variables. RESULTS: Most subjects were white, undergraduate females (63%), with 25% either overweight or obese. Treatment group completion rate for the curriculum was 84%. Over 15 months, the treatment group had significantly higher FV intake (+.5 cups/d) and physical activity participation (+270 metabolic equivalent minutes per week) than controls. For both groups, anthropometric values and stress increased, and fitness levels decreased. Gender differences were present for most variables. First-year males and females gained more weight than participants in other school years. CONCLUSION: A 10-week online nutrition and physical activity intervention to encourage competence in making healthful food and eating decisions had a positive, lasting effect on FV intake and maintained baseline levels of physical activity in a population that otherwise experiences significant declines in these healthful behaviors.

Identifying clusters of college students at elevated health risk based on eating and exercise behaviors and psychosocial determinants of body weight.

Weight gain and an increase in overweight and obesity in college students raise serious health concerns. Weight management interventions for college-age men and women might be more effective if they were tailored to subgroups of students with similar behavioral and psychosocial characteristics associated with body weight status. The purpose of this study was to use cluster analysis to identify homogenous subgroups of college-aged men and women enrolled in a weight gain prevention study (Project WebHealth) using baseline data collected in 2008. Project WebHealth was a 15-month nutrition and physical activity intervention designed to decrease the rate of unwanted weight gain in 1,689 college students at eight geographically diverse universities in the United States. Outcome measures included anthropometrics, fruit and vegetable intake, physical activity, cardiorespiratory fitness, and psychosocial variables associated with weight status in college students. Cluster analysis was performed separately by sex using a two-step clustering procedure using weight-related eating and exercise behaviors and psychosocial variables. Cluster groupings were validated against students' measured weight status and waist circumference as indicators of health risk. The study design was cross-sectional. Results showed that three similar clusters were identified for each sex. Validity of the cluster solution was supported by significant group differences in body mass index and waist circumference with the High Risk cluster at elevated health risk compared to the others. For men, variability in eating competence and cognitive restraint scores contributed most to the difference between clusters, whereas for women, emotional eating and uncontrolled eating scores did. These findings could be used to improve effectiveness of messages and interventions by tailoring them to subgroups of college students with similar behavioral and psychosocial characteristics associated with elevated health risk.