Implementing an Evidence-Based Functional Pain Assessment Scale in an Adult Inpatient Unit.

BACKGROUND: The focus on pain assessment using a single, one-dimension pain assessment scale can be problematic. Locally, challenges we faced with this were; a) pain was percieved as not being effectively managed, b) patients with chronic pain were not having their pain adequately controlled, and c) misconceptions and subsequent confusion between health care teams and patients related to what pain intensity scores mean to each individual. AIMS: The purpose of this paper is to describe an evidence-based practice project aiming at improving pain assessment through the implementation of a Functional Pain Scale (FPS) on an adult inpatient cardiothoracic unit. DESIGN: The Iowa Model-Revised and the Implementation Strategies for Evidence- Based Practice Guide served as the framework for this project. SETTING: Over an 18-month period at a academic tertiary medical center in the midwest. PARTICIPANTS/SUBJECTS: Staff and patients on an adult inpatient 48-bed medical and surgical cardiothoracic unit. METHODS: Following a synthesis of the evidence, implementation of the FPS required various strategies, such as, individualized patient and staff education, audit and feedback, a pain policy revision, and creating documentation in the electronic medical record. Evaluation of the FPS consisted of patient and staff surveys pre- and postimplementation to assess knowledge, attitudes, and behaviors. RESULTS: After the pilot period, over 75% of the patients preferred to use the FPS and almost all the patients found the scale easy to use. Nurses reported an increase in perception that pain documentation was complete, that the FPS allowed them to accurately document their patients' pain experience, and that their patients were well informed of their pain management plan. CONCLUSIONS: This project supports successful implementation of the FPS within nursing workflow. The goal of using the FPS is to change pain management discussions from an intensity reduction to meeting goals of care, aligning expectations, and creating common language among patients and providers.

The complexity of intestinal permeability: Assigning the correct BCS classification through careful data interpretation.

While the solubility parameter is fairly straightforward when assigning BCS classification, the intestinal permeability (Peff) is more complex than generally recognized. In this paper we emphasize this complexity through the analysis of codeine, a commonly used antitussive/analgesic drug. Codeine was previously classified as a low-permeability compound, based on its lower LogP compared to metoprolol, a marker for the low-high permeability class boundary. In contrast, high fraction of dose absorbed (Fabs) was reported for codeine, which challenges the generally recognized Peff-Fabs correlation. The purpose of this study was to clarify this ambiguity through elucidation of codeine's BCS solubility/permeability class membership. Codeine's BCS solubility class was determined, and its intestinal permeability throughout the small intestine was investigated, both in vitro and in vivo in rats. Codeine was found to be unequivocally a high-solubility compound. All in vitro studies indicated that codeine's permeability is higher than metoprolol's. In vivo studies in rats showed similar permeability for both drugs throughout the entire small-intestine. In conclusion, codeine was found to be a BCS Class I compound. No Peff-Fabs discrepancy is involved in its absorption; rather, it reflects the risk of assigning BCS classification based on merely limited physicochemical characteristics. A thorough investigation using multiple experimental methods is prudent before assigning a BCS classification, to avoid misjudgment in various settings, e.g., drug discovery, formulation design, drug development and regulation.

Serial infusions of low-dose ketamine for major depression.

BACKGROUND: Single infusions of ketamine have been used successfully to achieve improvement in depressed patients. Side effects during the infusions have been common. It is not known whether serial infusions or lower infusion rates result in greater efficacy. METHODS: Ten depressed patients were treated with twice weekly ketamine infusions of ketamine 0.5 mg/kg administered over 100 min until either remission was achieved or four infusions were given. Side effects were assessed with the Young Mania Rating Scale (YMRS) and the Brief Psychiatric Rating Scale (BPRS). Patients were followed naturalistically at weekly intervals for four weeks after completion of the infusions. RESULTS: Five of 10 patients achieved remission status. There were no significant increases on the BPRS or YMRS. Two of the remitting patients sustained their improvement throughout the four week follow-up period. CONCLUSIONS: Ketamine infusions at a lower rate than previously reported have demonstrated similar efficacy and excellent tolerability and may be more practically available for routine clinical care. Serial ketamine infusions appear to be more effective than a single infusion. Further research to test relapse prevention strategies with continuation ketamine infusions is indicated.

Low molecular weight amidoximes that act as potent inhibitors of lysine-specific demethylase 1.

The recently discovered enzyme lysine-specific demethylase 1 (LSD1) plays an important role in the epigenetic control of gene expression, and aberrant gene silencing secondary to LSD1 dysregulation is thought to contribute to the development of cancer. We reported that (bis)guanidines, (bis)biguanides, and their urea- and thiourea isosteres are potent inhibitors of LSD1 and induce the re-expression of aberrantly silenced tumor suppressor genes in tumor cells in vitro. We now report a series of small molecule amidoximes that are moderate inhibitors of recombinant LSD1 but that produce dramatic changes in methylation at the histone 3 lysine 4 (H3K4) chromatin mark, a specific target of LSD1, in Calu-6 lung carcinoma cells. In addition, these analogues increase cellular levels of secreted frizzle-related protein (SFRP) 2, H-cadherin (HCAD), and the transcription factor GATA4. These compounds represent leads for an important new series of drug-like epigenetic modulators with the potential for use as antitumor agents.

Polyamine-based small molecule epigenetic modulators.

Chromatin remodelling enzymes such as the histone deacetylases (HDACs) and histone demethylases such as lysine-specific demethylase 1 (LSD1) have been validated as targets for cancer drug discovery. Although a number of HDAC inhibitors have been marketed or are in human clinical trials, the search for isoform-specific HDAC inhibitors is an ongoing effort. In addition, the discovery and development of compounds targeting histone demethylases are in their early stages. Epigenetic modulators used in combination with traditional antitumor agents such as 5-azacytidine represent an exciting new approach to cancer chemotherapy. We have developed multiple series of HDAC inhibitors and LSD1 inhibitors that promote the re-expression of aberrantly silenced genes that are important in human cancer. The design, synthesis and biological activity of these analogues is described herein.

(Bis)urea and (bis)thiourea inhibitors of lysine-specific demethylase 1 as epigenetic modulators.

The recently discovered enzyme lysine-specific demethylase 1 (LSD1) plays an important role in the epigenetic control of gene expression, and aberrant gene silencing secondary to LSD1 overexpression is thought to contribute to the development of cancer. We recently reported a series of (bis)guanidines and (bis)biguanides that are potent inhibitors of LSD1 and induce the re-expression of aberrantly silenced tumor suppressor genes in tumor cells in vitro. We now report a series of isosteric ureas and thioureas that are also potent inhibitors of LSD1. These compounds induce increases in methylation at the histone 3 lysine 4 (H3K4) chromatin mark, a specific target of LSD1, in Calu-6 lung carcinoma cells. In addition, these analogues increase cellular levels of secreted frizzle-related protein (SFRP) 2 and transcription factor GATA4. These compounds represent an important new series of epigenetic modulators with the potential for use as antitumor agents.