ABSTRACT
Objective To explore the association between mild cognitive impairment (MCI) and the risk of falls in community populations, so as to provide a reference for preventing falls in the elderly. Methods 826 community residents aged 55 years and older were enrolled in Wuzhong, Ningxia; cognitive function was assessed during the participants attending the basic public health examination, and self-report falling events were observed through telephone call survey after half a year. The incidence of falls among different populations was compared using unconditional Logistic regression model. Results A total of 521 participants completed the follow-up study, and 127 of them met criteria of MCI at baseline. 32 participants reported falling occurred during follow-up with a incidence of 6.1% (32/521), and the incidence of falls was higher (8.85%,23/260) in females than that of males (3.45%,9/261) (RR=2.56, P=0.010). The incidence among MCI group (9.45%,12/127) was 1.86 times of that among non-MCI group (RR=1.86, P=0.073). Under the controlling of demographic variables (gender, age and education level), there was no association between MCI and falls (RR=1.41, P=0.382). Conclusions The incidence of falls in the elderly communities is common, and females has higher risk of falls than males. There is no statistical association between MCI and risk of falls. Further validation is needed with large-sample studies in the future.
ABSTRACT
This study was designed to investigate the inhibitory effects of regorafenib (REG) on the catalytic activities of 12 kinds of human UGT isoforms and human liver microsomes (HLM) in vitro. The broader potential of REG to perpetrate drug-drug interactions (DDI) arising from UGT enzyme inhibition is predicted by in vitro-vivo extrapolation (IV-IVE). Fifty mixed HLM and 12 kinds of recombinant UGTs were utilized as enzyme sources to evaluation the inhibitory effects of REG against UGTs. 4-Methylumbelliferone (4-MU) as a nonselective substrate of UGTs except for UGT1A4, N-(3-carboxypropyl)-4-hydroxy-1,8-napht-halimide (NCHN) and N-butyl-4-(4-hydroxyphenyl)-1,8-naphthalimide (NPHN) as the specific fluorescent substrate of UGT1A1, and trifluoperazine (TFP) as the specific substrate of UGT1A4. The half maximal inhibitory concentration (IC50) was calculated via the nonlinear regression analysis using Graphpad Prism 6.0, the inhibition kinetic types were selected and evaluated based on the intersection location of Lineweaver-Burk plot and Dixon plot, and Ki values were determined by the second plot of slopes. The potential DDI risk based on UGT1A1 inhibition was also evaluated through the in vitro parameters. The results demonstrated that REG displayed strong inhibitory effects against UGT1A1, 1A7, 1A9, and 2B7. The IC50 values were from 0.15 to 6.6 μmol·L-1 and Ki values from 0.027 to 14 μmol·L-1. The REG exerted competitive inhibition against UGT1A1-mediated 4-MU-O-glucuronidation and UGT1A1-mediated NPHN-O-glucuronidation, while the inhibition of NCHN-4-O-glucuronide by REG was suited to noncompetitive inhibition in both HLM and recombinant UGT1A1. Likewise, REG exhibited a mixed efficacy in inhibition of UGT1A7-, UGT1A9-, and UGT2B7-catalyzed 4-MU-O-glucuronidation. The AUC ratio of UGT1A1 specific substrates NPHN and NCHN can be increased by 101% to 302% and 13% to 109%, respectively. These results suggest that much caution should be exercised when REG is co-administered with UGT1A1 substrates.