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Purpose: Differential use of screening mammography may lead to biased detection of breast cancer. This study aimed to compare receipt of screening mammography and the incidence of screen-detected breast cancer between metformin and sulfonylurea initiators., Methods: We used 2006-2014 US Medicare claims to identify initiators of metformin or sulfonylurea aged 65+ years continuously enrolled in Parts A/B for ≥2 years pre-initiation and ≥2 years post-initiation. We reported frequencies of screening mammograms and screen-detected breast cancer in 1 year pre-initiation among all cohort members and in 1 year post-initiation among cancer-free cohort members. Weighted screening risk differences (RDs) were estimated comparing metformin to sulfonylurea group., Results: We identified 41,436 and 13,367 initiators of metformin and sulfonylurea, 35% and 24% of which had ≥1 screening mammogram in 1 year pre-initiation (weighted RD: 6 percentage points; 95% CI: 5 to 7), respectively. The weighted RD for screen-detected breast cancer associated with metformin was 0.00 percentage points (95% CI: -0.09 to 0.09). Among cancer-free cohort members, metformin initiators had 5 percentage points (95% CI: 4 to 6) and 0.11 percentage points (95% CI: -0.02 to 0.23) absolute risk excess of screening mammography and screen-detected breast cancer in 1 year post-initiation, compared with sulfonylurea initiators, respectively., Conclusions: Metformin initiators were more likely to receive screening mammograms than sulfonylurea initiators pre- and post-initiation, indicating possible detection bias due to differential screening mammography. Researchers should be aware of the potential for more screening mammograms pre- and post-initiation when interpreting the findings of metformin on breast cancer incidence. Copyright © 2017 John Wiley & Sons, Ltd., (Copyright © 2017 John Wiley & Sons, Ltd.)

Purpose: Few studies have examined patients with prediabetes in usual, "real-world" clinical practice settings. Among patients with impaired fasting glucose (IFG), we aimed to describe the rates of progression to diabetes and to examine the long-term reduction in diabetes risk associated with regression to normoglycemia at 1 year., Methods: The UK-based study included 120 055 non-diabetic patients in Clinical Practice Research Datalink from 2001 to 2012 aged 25+ years and with ≥1 fasting plasma glucose (FPG) test between ≥6.1 and <7.0 mmol/l indicating IFG who were followed for progression to diabetes. In a subgroup of 45 167 patients with IFG with subsequent FPG results 1 year later, we assessed the 1-year glycemic status change and estimated the relative hazard of diabetes comparing patients with regression to normoglycemia (IFG-normoglycemia) to those who remained in IFG (IFG-IFG) using a multivariable Cox model., Results: Among patients with IFG with over 414 649 person-years of follow-up, 52% received a subsequent FPG test, and 10% developed diabetes within 1 year after recognition of IFG. The incidence rate of diabetes was 5.86 (95% CI: 5.78 to 5.93) per 100 person-years. In the subgroup analysis, 31% of these patients remained in IFG, while 53% and 16% converted to normoglycemia or diabetes, respectively. The adjusted hazard ratio of developing diabetes was 0.33 (95% CI: 0.31 to 0.35) comparing IFG-normoglycemia to IFG-IFG., Conclusions: IFG is a high-risk state for diabetes. Regression to normoglycemia from IFG strongly reduces the long-term risk of developing diabetes. Our study also shows the feasibility of identifying patients with IFG in the Clinical Practice Research Datalink. Copyright © 2016 John Wiley & Sons, Ltd., (Copyright © 2016 John Wiley & Sons, Ltd.)

The pharmacokinetic disposition of a dietary cancer chemopreventive compound dibenzoylmethane (DBM) was studied in male Sprague-Dawley rats after intravenous (i.v.) and oral (p.o.) administrations. Following a single i.v. bolus dose, the mean plasma clearance (CL) of DBM was low compared with the hepatic blood flow. DBM displayed a high volume of distribution (Vss). The elimination terminal t1/2 was long. The mean CL, Vss and AUC0-∞/dose were similar between the i.v. 10 and 10 mg/kg doses. After single oral doses (10, 50 and 250 mg/kg), the absolute oral bioavailability (F*) of DBM was 7.4%-13.6%. The increase in AUC was not proportional to the oral doses, suggesting non-linearity. In silico prediction of oral absorption also demonstrated low DBM absorption in vivo. An oil-in-water nanoemulsion containing DBM was formulated to potentially overcome the low F* due to poor water solubility of DBM, with enhanced oral absorption. Finally, to examine the role of Nrf2 on the pharmacokinetics of DBM, since DBM activates the Nrf2-dependent detoxification pathways, Nrf2 wild-type (+/+) mice and Nrf2 knockout (-/-) mice were utilized. There was an increased systemic plasma exposure of DBM in Nrf2 (-/-) mice, suggesting that the Nrf2 genotype could also play a role in the pharmacokinetic disposition of DBM. Taken together, the results show that DBM has low oral bioavailability which could be due in part to poor water solubility and this could be overcome by a nanotechnology-based drug delivery system and furthermore the Nrf2 genotype could also play a role in the pharmacokinetics of DBM., (Copyright © 2010 John Wiley & Sons, Ltd.)