Project #82: HFWH Vertical Treatment Zone

Problem Statement: Limited Emergency Department bed capacity and increased acuity resulted in increased left without completing service (LWCS) resulting in increased patient safety risk. Goal: Design a new patient throughput workflow to provide safe, timely and quality patient-centered care resulting in decreased LWSC, decreased arrival to provider times, decreased LOS of the discharged patient, and increased patient satisfaction.https://scholarlycommons.henryford.com/qualityexpo2023/1007/thumbnail.jp

Incidence and Risk of QTc Interval Prolongation among Cancer Patients Treated with Vandetanib: A Systematic Review and Meta-analysis

Vandetanib is a multikinase inhibitor that is under assessment for the treatment of various cancers. QTc interval prolongation is one of the major adverse effects of this drug, but the reported incidence varies substantially among clinical trials. We performed a systematic review and meta-analysis to obtain a better understanding in the risk of QTc interval prolongation among cancer patients administered vandetanib.Eligible studies were phase II and III prospective clinical trials that involved cancer patients who were prescribed vandetanib 300 mg/d and that included data on QTc interval prolongation. The overall incidence and risk of QTc interval prolongation were calculated using random-effects or fixed-effects models, depending on the heterogeneity of the included studies. Nine trials with 2,188 patients were included for the meta-analysis. The overall incidence of all-grade and high-grade QTc interval prolongation was 16.4% (95% CI, 8.1-30.4%) and 3.7% (8.1-30.4%), respectively, among non-thyroid cancer patients, and 18.0% (10.7-28.6%) and 12.0% (4.5-28.0%), respectively, among thyroid cancer patients. Patients with thyroid cancer who had longer treatment duration also had a higher incidence of high-grade events, with a relative risk of 3.24 (1.57-6.71), than patients who had non-thyroid cancer. Vandetanib was associated with a significantly increased risk of all-grade QTc interval prolongation with overall Peto odds ratios of 7.26 (4.36-12.09) and 5.70 (3.09-10.53) among patients with non-thyroid cancer and thyroid cancer, respectively, compared to the controls.Treatment with vandetanib is associated with a significant increase in the overall incidence and risk of QTc interval prolongation. Different cancer types and treatment durations may affect the risk of developing high-grade QTc interval prolongation

Tubulin-binding dibenz[c,e]oxepines: Part 2 Structural variation and biological evaluation as tumour vasculature disrupting agents

5,7-Dihydro-3,9,10,11-tetramethoxybenz[c,e]oxepin-4-ol 1, prepared from a dibenzyl ether precursor via Pd-catalysed intramolecular direct arylation, possesses broad-spectrum in vitro cytotoxicity towards various tumour cell lines, and induces vascular shutdown, necrosis and growth delay in tumour xenografts in mice at sub-toxic doses. The biological properties of 1 and related compounds can be attributed to their ability to inhibit microtubule assembly at the micromolar level, by binding reversibly to the same site of the tubulin αβ-heterodimer as colchicine 2 and the allocolchinol, N-acetylcolchinol 4

Targeting histone deacetyalses in the treatment of B- and T-cell malignancies

HDAC inhibitors (HDACI) are now emerging as one of the most promising new classes of drugs for the treatment of select forms of non-Hodgkin’s lymphoma (NHL). They are particularly active in T-cell lymphomas, possibly hodgkin’s lymphoma and indolent B cell lymphomas. Presently, two of these agents, vorinostat and romidepsin, have been approved in the US for the treatment of relapsed and refractory cutaneous T cell lymphomas (CTCL). Initially, these agents were developed with the idea that they affected transcriptional activation and thus gene expression, by modulating chromatin condensation and decondensation. It is now clear that their effects go beyond chromatin and by affecting the acetylation status of histones and other intra-cellular proteins, they modify gene expression and cellular function via multiple pathways. Gene expression profiles and functional genetic analysis has led to further understanding of the various molecular pathways that are affected by these agents including cell cycle regulation, pathways of cellular proliferation, apoptosis and angiogenesis all important in lymphomagenesis. There is also increasing data to support the effects of these agents on T cell receptor and immune function which may explain the high level of activity of these agents in T cell lymphomas and hodgkin’s lymphoma. There is ample evidence of epigenetic dysregulation in lymphomas which may underlie the mechanisms of action of these agents but how these agents work is still not clear. Current HDAC inhibitors can be divided into at least four classes based on their chemical structure. At present several of these HDAC inhibitors are in clinical trials both as single agents and in combination with chemotherapy or other biological agents. They are easy to administer and are generally well tolerated with minimal side effects. Different dosing levels and schedules and the use of isospecific HDAC inhibitors are some of the strategies that are being employed to increase the therapeutic effect of these agents in the treatment of lymphomas. There may also be class differences that translate into specific activity against different lymphoma. HDAC inhibitors will likely be incorporated into combinations of targeted therapies both in the upfront and relapsed setting for lymphomas

Anion-exchange resin-based desulfurization process

Under the current grant (FG22-90PC90309), the University of Tennessee Space Institute (UTSI) will carry out the necessary bench scale experiments to further develop it anion-exchange, resin-based desulfurization concept to desulfurize alkali metal sulfates. In particular, it is planned to screen commercially available resins and then carry out process optimization work with three selected resins. Further optimization of the resin regeneration step as well as evaluation of the effect of various performance enhancers will then be carried out with one selected resin. A process schematic, to be developed based on the bench scale results, will be used to estimate the related economics. Some limited scope testing will also be carried out using the spent-seed and sorbent materials obtained from both the coal-fired magnetohydrodynamics (MHD) and the in-duct sorbent injection pilot scale facilities. During this reporting period, 90% of the planned batch mode screening experiments for the eleven samples of candidate resins were completed. Preliminary evaluation of the resulting data is continuing in order to select a smaller number (3--4) of samples for screening in the fixed-bed setup. The installation of the semi-automated fixed-bed setup is about 70% complete and shakedown experiments will be started in 3--4 weeks. Progress made in relation to these activities is presented below. 2 figs., 3 tabs

Anion-exchange resin-based desulfurization process

Under DOE Grant No. FG22-90PC90309, the University of Tennessee Space Institute (UTSI) is contracted to further develop its anion-exchange, resin-based desulfurization concept to desulfurize alkali metal sulfates. From environmental as well as economic viewpoints, it is necessary to remove soluble sulfates from the wastes created by flue gas desulfurization systems. In order to do this economically, a low-cost desulfurization process for spent sorbents is necessary. UTSI's anion-exchange resin-based desulfurization concept is believed to satisfy these requirements

Anion-exchange resin-based desulfurization process. Quarterly technical progress report, October 1, 1991--December 31, 1991

The University of Tennessee Space Institute (UTSI) has a Department of Energy grant to further develop the Institute`s anion-exchange resin-based flue gas, desulfurization concept. The developmental program proposed includes screening of commercially available resins to select three candidate resins for further study. These three resins will undergo a series of experiments designed to test the resins` performance under different process conditions (including the use of spent MHD seed material). The best of these resins will be used in optimizing the regeneration step and in testing the effects of performance enhancers. The process schematic developed from the results will be used to estimate the related economics