Reducing Immunogenicity of Pegloticase With Concomitant Use of Mycophenolate Mofetil in Patients With Refractory Gout: A Phase II, Randomized, Double-Blind, Placebo-Controlled Trial.

OBJECTIVE: Pegloticase is used for the treatment of severe gout, but its use is limited by immunogenicity. This study was undertaken to evaluate whether mycophenolate mofetil (MMF) prolongs the efficacy of pegloticase. METHODS: Participants were randomized 3:1 to receive 1,000 mg MMF twice daily or placebo for 14 weeks, starting 2 weeks before receiving pegloticase and continuing while receiving intravenous pegloticase 8 mg biweekly for 12 weeks. Participants then received pegloticase alone from week 12 to week 24. The primary end points were the proportion of patients who sustained a serum urate level of ≤6 mg/dl at 12 weeks and the rate of adverse events (AEs). Secondary end points included 24-week durability of serum urate level ≤6 mg/dl. Fisher's exact test and Wilcoxon's 2-sample test were used for analyses, along with Kaplan-Meier estimates and log rank tests. RESULTS: A total of 32 participants received ≥1 dose of pegloticase. Participants were predominantly men (88%), with a mean age of 55.2 years, mean gout duration of 13.4 years, and mean baseline serum urate level of 9.2 mg/dl. At 12 weeks, a serum urate level of ≤6 mg/dl was achieved in 19 (86%) of 22 participants in the MMF arm compared to 4 (40%) of 10 in the placebo arm (P = 0.01). At week 24, the serum urate level was ≤6 mg/dl in 68% of MMF-treated patients versus 30% of placebo-treated patients (P = 0.06), and rates of AEs were similar between groups, with more infusion reactions occurring in the placebo arm (30% versus 0%). CONCLUSION: Our findings indicate that MMF therapy with pegloticase is well tolerated and shows a clinically meaningful improvement in targeted serum urate level of ≤6 mg/dl at 12 and 24 weeks. This study suggests an innovative approach to pegloticase therapy in gout.

Gender differences in prednisone adverse effects: Survey result from the MG registry.

OBJECTIVE: Prednisone is a first-line immunosuppressive treatment for myasthenia gravis (MG), whereas short-term and long-term adverse effects (AEs) are a limiting factor in its usage. METHOD: The MG patient registry is a patient-driven, nation-wide database with patients of age ≥18 years, who were diagnosed with MG and live in the United States. Custom-designed "prednisone-steroid use and MG" survey was sent out to MG registry participants as part of semi-annual follow-up. Data were collected and analyzed for frequency. RESULTS: A total of 398 MG participants (21% response rate) completed the survey, including 173 men and 225 women. Among them, 298 reported current (174) or past (288) prednisone intake. Current prednisone dosage varied from 0.5 to 75 mg (median 10 mg, IQR 7-20), dosing frequency was daily in 132 (76%) and every other day in 31 (18%). Peak prednisone dose was commonly between 25 mg and 60 mg (Median 50 mg, IQR 25-60); however, doses more than 60 mg daily were reported in 59 (20%). Prednisone AEs were reported more commonly in women (95% vs 81%, p < 0.0001). Women reported more intolerable AEs (77% vs 50%, p < 0.00001) and less willingness to accept a dose increase (26% vs 44%, p = 0.03) compared with men. CONCLUSIONS: Prednisone is commonly used in the treatment of MG, with highly variable dosages and dosing frequencies reflecting the absence of a standard guideline. Intolerable AEs were more commonly reported among women and was associated with unwillingness to accept a dose increase. Consensus guidelines and their validation are required to guide prednisone treatment for MG.

Body mass index and dietary intake among Head Start children and caregivers.

BACKGROUND: The US Head Start program serves low-income preschoolers and their caregivers and provides an opportunity for assessment and intervention on obesity. We sought to determine the prevalence of obesity among children and their caregivers and to identify variables that are associated with child body mass index (BMI) z scores and caregiver BMI. DESIGN/SETTING: Cross-sectional data on diet and BMI from 770 caregiver-child dyads recruited from 57 Head Start centers in Alabama and Texas. METHODS: Height and weight of each caregiver and child were measured using standardized protocols. Dietary intakes of caregiver-child dyads were collected using three 24-hour dietary recalls and Block food frequency questionnaires. Data were collected between September 2004 and November 2005. The larger Food Pyramid categories were divided into 17 food consumption groups and tested for their association with child BMI z scores. Analysis of variance was used to test if food groups were significantly associated with child BMI z score. RESULTS: The prevalence of obesity among children was 18.4%, 24.3%, and 37.3% among black, Hispanic, and white children, respectively (P<0.0001), whereas it was 58.3%, 41.4%, and 41.6% among black, Hispanic, and white caregivers, respectively (P<0.0001). Child BMI z scores and caregiver BMIs were correlated (r=0.16, P<0.0001). In multivariable models, children were 1.90 (95% confidence interval 1.31-2.74) times more likely to have BMI ≥95th percentile if their caregiver was obese. Five variables (fruits, unsweetened beverages, low-fat dairy, race, and caregiver's BMI) were significantly associated with child BMI z scores. Fruits were inversely related, whereas unsweetened beverages, low-fat dairy, and caregiver's BMI were positively associated with child BMI z score (P<0.03). Compared to whites, black and Hispanic children had lower BMI z scores (P<0.05). CONCLUSIONS: The high prevalence of obesity in this population together with the observed inverse association between fruit consumption and BMI, if replicated in other studies, suggests that interventions that promote fruit consumption could have beneficial effects on child BMI.

Hi5+: systematic development of a family intervention to increase fruit and vegetable intake.

This article describes the development of a peer-led home-based intervention to increase fruit and vegetable (FV) intake and family interaction among fourth graders and their families. Hi5+ intervention content and delivery strategies were developed using two complementary processes: cognitive mapping (CM), a consumer-based approach to identifying salient issues, and intervention mapping (IM), a comprehensive planning model. Step 1 involved creating plans to guide the design, implementation, and evaluation of Hi5+. We delineated our performance objectives and then prioritized those determinants we felt were most salient and changeable. Step 2 involved selecting and utilizing cognitive and behavioral theory constructs to develop intervention methods and strategies. Step 3 involved designing and pilot testing the instructional materials and other intervention components. Step 4 entailed developing plans for program adoption and implementation, while the final step (Step 5) involved creating a comprehensive evaluation plan. Implications of this multistep approach to intervention development are discussed.