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Predictors of poor response to urate-lowering therapy in patients with gout and hyperuricemia: a post-hoc analysis of a multicenter randomized trial.
Mu, Z, Wang, W, Wang, J, Lv, W, Chen, Y, Wang, F, Yu, X, Wang, Y, Cheng, B, Wang, Z
Clinical rheumatology. 2019;(12):3511-3519
Abstract
INTRODUCTION Clinical guidelines have recommended a target of serum uric acid (SUA) level below 6.0 mg/dL for the urate-lowering therapy (ULT) of gout patients, but there are still a high proportion of patients failing to achieve the therapeutic target above. This study aimed to identify possible predictors of poor response to ULT in gout patients. METHODS We performed a post-hoc analysis of a multicenter randomized double-blind trial which assessed the efficacy of febuxostat in patients with hyperuricemia (serum urate level ≥ 8.0 mg/dL) and gout. Demographic characters and baseline data including SUA levels were collected. Poor response to ULT was defined as average SUA after ULT was more than 6.0 mg/dL. Factors associated with poor response to ULT in gout patients were analyzed, and multivariate logistic regression analysis was also carried out to find out those independent predictors. RESULTS A total of 370 patients were enrolled in this post-hoc analysis. Compared with those with good response to ULT, patients with poor response to ULT had younger age (P < 0.001), higher proportion of obesity (P = 0.003), higher proportion of statins use (P = 0.019), higher body mass index (BMI) (P < 0.001), higher baseline SUA (P < 0.001), higher proportion of males (P = 0.001), higher alanine transaminase (P < 0.001), higher aspartate transaminase (P = 0.017), higher total cholesterol (P = 0.005), higher triglyceride (P = 0.042), and higher low density lipoprotein (P = 0.037). Multivariate logistic regression analysis showed that younger age (odds ratio (OR) = 0.965, 95% CI 0.943-0.987, P = 0.002), higher BMI (OR = 1.133, 95% CI 1.049-1.224, P = 0.001), higher baseline SUA (OR = 1.006, 95% CI 1.002-1.009, P = 0.001), and no application of febuxostat therapy (OR = 0.41, 95% CI 0.25-0.68, P < 0.001) were independent predictors of poor response to ULT in patients with gout. CONCLUSION In patients with gout and hyperuricemia, younger age, higher BMI, and higher baseline SUA are predictors of poor response to ULT. These findings could help physicians better identify patients who may fail in ULT and give individualized treatment precisely. TRIAL REGISTRATION The trial was registered at chinadrugtrials.org.cn in 2012 (CTR20130172).Key Points• A post-hoc analysis of a multicenter randomized double-blind trial which assessed the efficacy of febuxostat in patients with hyperuricemia and gout was performed.• Multivariate logistic regression analysis showed that younger age, higher BMI, and higher baseline SUA are predictors of poor response to urate-lowering therapy.
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Body mass index (BMI) as predictor of ALSFRS-R score decline in ALS patients.
Reich-Slotky, R, Andrews, J, Cheng, B, Buchsbaum, R, Levy, D, Kaufmann, P, Thompson, JL
Amyotrophic lateral sclerosis & frontotemporal degeneration. 2013;(3):212-6
Abstract
Recent studies of amyotrophic lateral sclerosis (ALS) suggest that body mass index (BMI) predicts patients' survival in a curvilinear manner. We sought to determine the relationship of initial BMI to decline in the revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) score over time. We used data from the high dose Coenzyme-Q10 in ALS (QALS) clinical trial, with in-person ALSFRS-R interviews at baseline and nine months (n = 150). Multiple regression analysis allowed adjustment for a range of predictors. The final analysis, adjusted for age and FVC, indicated a significant, non-linear association of BMI with the change of ALSFRS-R over time (p < 0.01). The smallest decline was at BMI of 30. Among non-obese patients (BMI < 30, n = 126), higher BMI was associated with slower ALSFRS-R decline (p = 0.03). Among obese patients (BMI ≥ 30, n = 24), higher BMI was associated, although not significantly, with faster decline (p = 0.17). In conclusion, for ALS patient with BMI less than 30, higher initial BMI predicts slower functional decline. For patients with BMI greater than 30, higher initial BMI predicts more rapid decline. These results indicate that previous, apparently contradictory results can be reconciled, and suggest that initial BMI may help predict disease progression in ALS patients.
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A randomized, controlled, double-blind, pilot study of milk thistle for the treatment of hepatotoxicity in childhood acute lymphoblastic leukemia (ALL).
Ladas, EJ, Kroll, DJ, Oberlies, NH, Cheng, B, Ndao, DH, Rheingold, SR, Kelly, KM
Cancer. 2010;(2):506-13
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Abstract
BACKGROUND Despite limited preclinical and clinical investigations, milk thistle (MT) is often used for the treatment of chemotherapy-associated hepatotoxicity. Limited treatment options exist for chemotherapy-related hepatoxicity. Given the wide use of MT, the authors investigated MT in both the laboratory and a clinical setting. METHODS In a double-blind study, children with acute lymphoblastic leukemia (ALL) and hepatic toxicity were randomized to MT or placebo orally for 28 days. Liver function tests were evaluated during the study period. To assess MT in vitro, the authors evaluated supratherapeutic concentrations in an ALL cell line. RESULTS Fifty children were enrolled. No significant differences in frequency of side effects, incidence and severity of toxicities, or infections were observed between groups. There were no significant changes in mean amino alanine transferase (ALT), aspartate amino transferase (AST), or total bilirubin (TB) at Day 28. At Day 56, the MT group had a significantly lower AST (P = .05) and a trend toward a significantly lower ALT (P = .07). Although not significantly different, chemotherapy doses were reduced in 61% of the MT group compared with 72% of the placebo group. In vitro experiments revealed no antagonistic interactions between MT and vincristine or L-asparaginase in CCRF-CEM cells. A modest synergistic effect with vincristine was observed. CONCLUSIONS In children with ALL and liver toxicity, MT was associated with a trend toward significant reductions in liver toxicity. MT did not antagonize the effects of chemotherapy agents used for the treatment of ALL. Future study is needed to determine the most effective dose and duration of MT and its effect on hepatotoxicity and leukemia-free survival.