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Objective: The aim of this study is to define the association between a genetic risk score (GRS) that combined the effect of multiple BMI-associated variants and gestational weight trajectory. Because pregnancy is a state of sympathetic activation, the association between gestational weight trajectory and variants in adrenergic pathways previously associated with weight was examined., Methods: In a previously defined cohort of pregnant women with (n = 1,504) and without gestational diabetes (GDM) (n = 435), weight trajectory was calculated using all weights during pregnancy. A GRS for BMI (GRS BMI ) was calculated using 31 common variants associated with BMI, and 10 variants in the adrenergic pathways were genotyped. Clinical and genetic factors were studied using generalized linear models., Results: Prepregnancy BMI was associated with the GRS BMI (P = 9.3 × 10 -11 ) and parity (P = 4.54 × 10 -17 ). The GRS BMI was associated with gestational weight trajectory in women with and without GDM (P = 0.041 and P < 0.0001, respectively); however, when prepregnancy BMI was included in the models, the associations disappeared (P > 0.05). Variants in adrenergic genes were not associated with gestational weight trajectory., Conclusions: A GRS for BMI was associated with prepregnancy BMI but was not independently associated with gestational weight trajectory in women with and without GDM. Selected variants in adrenergic genes were not associated with gestational weight trajectory., (© 2019 The Obesity Society.)

Objective: Low-dose aspirin prevents platelet aggregation by suppressing thromboxane A2 (TXA2 ) synthesis. However, in some individuals TXA2 suppression by aspirin is impaired, indicating suboptimal inhibition of platelet cyclooxygenase 1 (COX-1) by aspirin. Because patients with systemic lupus erythematosus (SLE) have increased risk of thrombotic events, many receive aspirin; however, the efficacy of aspirin in SLE has not been determined. We examined the hypothesis that aspirin response is impaired in SLE., Methods: We assessed the effect of aspirin by measuring concentrations of the stable metabolite of TXA2 , serum thromboxane B2 (sTXB2 ), before and after treatment with daily aspirin (81 mg) for 7 days in 34 patients with SLE and 36 control subjects. The inability to suppress sTXB2 synthesis to <10 ng/ml represents suboptimal inhibition of platelet COX-1 by aspirin., Results: Aspirin almost completely suppressed sTXB2 in control subjects to median 1.5 ng/ml (interquartile range [IQR] 0.8-2.7) but had less effect in patients with SLE (median 3.1 ng/ml [IQR 2.2-5.3]) (P = 0.002). A suboptimal effect of aspirin was present in 15% (5 of 34) of the patients with SLE but not in control subjects (0 of 36) (P = 0.023). Incomplete responders were more likely to have metabolic syndrome (P = 0.048), obesity (P = 0.048), and higher concentrations of C-reactive protein (CRP) (P = 0.018)., Conclusion: The pharmacologic effect of aspirin is suboptimal in 15% of patients with SLE but in none of the control subjects, and the suboptimal response was associated with metabolic syndrome, obesity, and higher CRP concentrations., (Copyright © 2014 by the American College of Rheumatology.)

Objective: We tested the hypothesis that initiation of tumor necrosis factor α (TNFα) antagonists reduced the risk of fractures compared to nonbiologic comparators in patients with autoimmune diseases., Methods: Using 4 large administrative databases, we assembled retrospective cohorts of patients with autoimmune diseases who initiated either a TNFα antagonist or a nonbiologic medication. We identified 3 mutually exclusive disease groups: rheumatoid arthritis (RA), inflammatory bowel disease (IBD), and a combined group: psoriasis (PsO), psoriatic arthritis (PsA), or ankylosing spondylitis (AS). We used baseline covariate data to calculate propensity scores (PS) for each disease group and used Cox regression to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs). We compared the risk of combined hip, radius/ulna, humerus, or pelvic fractures between PS-matched cohorts of new users of TNFα antagonists and nonbiologic comparators., Results: We identified 9,020, 2,014, and 2,663 new PS-matched episodes of TNFα antagonist and nonbiologic comparator use in RA, IBD, and PsO-PsA-AS cohorts, respectively. The risk of combined fractures was similar between new users of TNFα antagonists and nonbiologic comparators for each disease (HR 1.17, 95% CI 0.91-1.51; HR 1.49, 95% CI 0.72-3.11; and HR 0.92, 95% CI 0.47-1.82 for RA, IBD, and PsO-PsA-AS, respectively). In RA, the risk of combined fractures was associated with an average daily dosage of prednisone equivalents >10 mg/day at baseline compared with no glucocorticoid (HR 1.54, 95% CI 1.03-2.30)., Conclusion: The risk of fractures did not differ between initiators of a biologic agent and a nonbiologic comparator for any disease studied. Among RA patients, use of >10 mg/day of prednisone equivalents at baseline increased the fracture risk., (Copyright © 2013 by the American College of Rheumatology.)

Objective. We hypothesized that initiation of a new disease-modifying antirheumatic drug (DMARD) for treatment of rheumatoid arthritis (RA) would decrease the use of corticosteroids, nonsteroidal antiinflammatory drugs (NSAIDs), and narcotics.Methods. Using administrative databases, we assembled 4 retrospective cohorts of RA patients (1998-2005) and identified 5 groups initiating DMARD regimens: methotrexate (MTX) with (new MTX) or without (first MTX) use of other nonbiologic DMARDs in the previous year; new hydroxychloroquine (HCQ) and/or sulfasalazine (SSZ; new HCQ/SSZ)and new leflunomide (new LEF), both with previous use of MTX; and new tumor necrosis factor α (TNFα) antagonists(new anti-TNF). We compared within-person differences in any use of cotherapies (≥ prescription) between the 6 months before and the 6-12 months after DMARD initiation.Results. Among 32,476 DMARD initiators, the prevalence of corticosteroid, NSAID, and narcotic use increased by 15%, 5%,and 6%, respectively, in the 6 months before initiation compared to the previous 6 months, suggesting worsening of the disease. In the 6-12 months after initiation for most initiator groups, more patients stopped using corticosteroids and NSAIDs than started, with overall decreases of 8.9% (95% confidence interval [95% CI] 8.4-9.4%) for corticosteroids and 12.9% (95%CI 12.3-13.4%) for NSAIDs. The proportion of narcotic users changed little (overall decrease of 2.5%; 95% CI 1.9-3.0%).Conclusion. Use of all 3 cotherapies increased in the 6 months before initiation of new DMARD regimens for RA. Use of corticosteroids and NSAIDs decreased modestly 6-12 months after initiation, but there was only a very small decrease in narcotic use. These differential changes require further study.