Use of Evidence-Based Interventions and Implementation Strategies to Increase Colorectal Cancer Screening in Federally Qualified Health Centers

While colorectal cancer (CRC) screening rates have been increasing in the general population, rates are considerably lower in Federally Qualified Health Centers (FQHCs), which serve a large proportion of uninsured and medically vulnerable patients. Efforts to screen eligible patients must be accelerated if we are to reach the national screening goal of 80% by 2018 and beyond. To inform this work, we conducted a survey of key informants at FQHCs in eight states to determine which evidence-based interventions (EBIs) to promote CRC screening are currently being used, and which implementation strategies are being employed to ensure that the interventions are executed as intended. One hundred and forty-eight FQHCs were invited to participate in the study, and 56 completed surveys were received for a response rate of 38%. Results demonstrated that provider reminder and recall systems were the most commonly used EBIs (44.6%) while the most commonly used implementation strategy was the identification of barriers (84.0%). The mean number of EBIs that were fully implemented at the centers was 2.4 (range 0–7) out of seven. Almost one-quarter of respondents indicated that their FQHCs were not using any EBIs to increase CRC screening. Full implementation of EBIs was correlated with higher CRC screening rates. These findings identify gaps as well as the preferences and needs of FQHCs in selecting and implementing EBIs for CRC screening.     

Nephrotoxicity and Kidney Transport Assessment on 3D Perfused Proximal Tubules

Proximal tubules in the kidney play a crucial role in reabsorbing and eliminating substrates from the body into the urine, leading to high local concentrations of xenobiotics. This makes the proximal tubule a major target for drug toxicity that needs to be evaluated during the drug development process. Here, we describe an advanced in vitro model consisting of fully polarized renal proximal tubular epithelial cells cultured in a microfluidic system. Up to 40 leak-tight tubules were cultured on this platform that provides access to the basolateral as well as the apical side of the epithelial cells. Exposure to the nephrotoxicant cisplatin caused a dose-dependent disruption of the epithelial barrier, a decrease in viability, an increase in effluent LDH activity, and changes in expression of tight-junction marker zona-occludence 1, actin, and DNA-damage marker H2A.X, as detected by immunostaining. Activity and inhibition of the efflux pumps P-glycoprotein (P-gp) and multidrug resistance protein (MRP) were demonstrated using fluorescence-based transporter assays. In addition, the transepithelial transport function from the basolateral to the apical side of the proximal tubule was studied. The apparent permeability of the fluorescent P-gp substrate rhodamine 123 was decreased by 35% by co-incubation with cyclosporin A. Furthermore, the activity of the glucose transporter SGLT2 was demonstrated using the fluorescent glucose analog 6-NBDG which was sensitive to inhibition by phlorizin. Our results demonstrate that we developed a functional 3D perfused proximal tubule model with advanced renal epithelial characteristics that can be used for drug screening studies.