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OBJECTIVE To compare uptake in the ordering of biosimilars at a Veterans' Affairs medical center (VAMC) to that at an academic medical center, where institutional incentives for infused medications differ. METHODS We performed a cross-sectional study of medical record data and estimated institutional financial incentives at two medical centers in Philadelphia 1) the University of Pennsylvania Health System (UPHS) and 2) the local VAMC. All ordering events for filgrastim or infliximab products were quantified over time, stratified by product (biosimilar versus reference product) and center. Financial incentives to the institutions over time were determined based on actual drug costs for the VAMC and average sales prices (ASPs) and Medicare Part B reimbursement rates for UPHS. RESULTS There were 15,761 infusions of infliximab, of which 99% were for the reference product. There was sharper decline in use of reference products at the VAMC; 62% of the 446 infliximab infusions ordered at the VAMC were for the reference product. ASPs were consistently lower for biosimilar infliximab products, but the estimated institutional financial incentives remained similar over time for biosimilar and reference infliximab at UPHS. At the VAMC, the costs for 100 mg vials of reference infliximab and infliximab-abda were $623.48 and $115.58, respectively a $507.90 (81%) savings per vial. CONCLUSIONS The uptake of infliximab biosimilars has been slow at an academic medical center, compared to a nearby VAMC, where financial savings are realized by the institution from its use. Slow adoption of biosimilar medications may impact the rates of decline in costs. This article is protected by copyright. All rights reserved.Cationic polymers exhibit high cytotoxicity via strong interaction with cell membranes. To reduce cell membrane damage, a hydrophilic polymer is introduced to the cationic nanoparticle surface. The hydrophilic polymer coating of cationic nanoparticles resulted in a nearly neutral nanoparticle. https://www.selleckchem.com/products/Beta-Sitosterol.html These particles are applied to mouse fibroblast (3T3) and human cervical adenocarcinoma (Hela) cells. Interestingly, nanoparticles with a long cationic segment decrease cell activity regardless of cell type, while those with a short segment only affect 3T3 cell activity at lower concentrations less than 500 µg mL-1 . Most nanoparticles are located inside 3T3 cells but on the cell membrane of Hela cells. The short cationic nanoparticle shows negligible cell membrane damage despite its high accumulation on Hela cell membranes. Cell activity changed by hydrophilic polymer-coated cationic nanoparticles is caused by incorporated nanoparticle accumulation in the cells, not cell membrane damage. To suppress the cytotoxicity from the cationic polymer, cationic nanoparticle needs to completely cover with hydrophilic polymer so as not to exhibit the cationic effect and applies to cell with low concentrations to reduce the nonselective cytotoxicity from the cationic polymer. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.BACKGROUND Although breast cancer screening reduces breast cancer mortality at the population level, subgroups of women may benefit differently. We investigated the impact of health status on the effect of breast cancer screening. METHODS The study included 181 299 women invited in two population-based screening programs in Denmark and 1 526 446 control subjects, followed from April 1981 to December 2014. Poisson regressions were used to compare the observed breast cancer mortality rate in women invited to screening with the expected rate in the absence of screening among women with and without chronic diseases. Chronic diseases were defined as any diagnosis in the Charlson Comorbidity Index during 4 years before the first invitation to screening. RESULTS Almost 10% of women had chronic diseases before first invitation to screening. Whereas we observed a reduction in breast cancer mortality following invitation to screening of 28% (95% CI, 20% to 35%) among women without chronic diseases, only a 7% (95% CI, -39% to 37%) reduction was seen for women with chronic diseases (P-value for interaction = .22). For participants, the reduction, corrected for selection bias, was 35% (95% CI 16% to 49%) for women without, and 4% (95% CI -146% to 62%) for women with chronic diseases (P-value for interaction = .43). CONCLUSION Our data indicate a marginal effect of mammography screening on breast cancer mortality in women with chronic diseases. If our results are confirmed in other populations, the presence of chronic diseases will be an important factor to take into consideration in personalized screening. © 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.OBJECTIVE To develop and validate a preoperative nomogram to predict pathological locally advanced disease (pLAD) of clinically localized upper urinary tract urothelial carcinoma (UTUC) treated with extirpative surgery. METHODS In total, 1101 patients with cN0M0 UTUC (development cohort, n = 604; validation cohort, n = 497) from 2 independent academic databases were retrospectively analyzed. pLAD was defined as pT3/4 and/or pN+. Multivariate logistic regression was used to develop a nomogram. The accuracy of the nomogram was evaluated with a receiver operating characteristic curve, calibration plot, and decision curve analysis. RESULTS The development and validation cohorts comprised 204 (33.8%) and 178 (35.8%) patients with pLAD, respectively. The multivariate analyses showed that the neutrophil-to-lymphocyte ratio (hazard ratio [HR], 2.27; P less then .001), chronic kidney disease (HR, 1.56; P = .032), tumor location (HR, 1.60; P = .029), hydronephrosis (HR, 2.71; P less then .001), and local invasion on imaging (HR, 8.59; P less then .001) were independent predictive factors. After bootstrapping, a well-calibrated nomogram achieved discriminative accuracy of 0.77 in the development cohort. The decision curve analysis demonstrated improved risk prediction against threshold probabilities (≥8%) of pLAD. These results were consistent in the validation cohort. CONCLUSION Our novel nomogram allows for more highly accurate prediction of pLAD of UTUC. This nomogram integrates standard imaging and laboratory factors that help to identify patients who will benefit from preoperative chemotherapy, extended lymph node dissection, or both. © 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
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