No abstract

Unexpected drug activities discovered during clinical testing establish the need for better characterization of compounds in human disease-relevant conditions early in the discovery process. Here, we describe an approach to characterize drug function based on statistical analysis of protein expression datasets from multiple primary human cell-based models of inflammatory disease. This approach, termed Biologically Multiplexed Activity Profiling (BioMAP), provides rapid characterization of drug function, including mechanism of action, secondary or off-target activities, and insights into clinical phenomena. Using three model systems containing primary human endothelial cells and peripheral blood mononuclear cells in different environments relevant to vascular inflammation and immune activation, we show that BioMAP profiles detect and discriminate multiple functional drug classes, including glucocorticoids; TNF-alpha antagonists; and inhibitors of HMG-CoA reductase, calcineurin, IMPDH, PDE4, PI-3 kinase, hsp90, and p38 MAPK, among others. The ability of cholesterol lowering HMG-CoA reductase inhibitors (statins) to improve outcomes in rheumatic disease patients correlates with the activities of these compounds in our BioMAP assays. In addition, the activity profiles identified for the immunosuppressants mycophenolic acid, cyclosporin A, and FK-506 provide a potential explanation for a reduced incidence of posttransplant cardiovascular disease in patients receiving mycophenolic acid. BioMAP profiling can allow integration of meaningful human biology into drug development programs.

We present a case series of seven patients with an established diagnosis of heart failure enrolled in a transitional care program that were treated with intravenous diuretic therapy in the outpatient setting. The patients presented in this cases series were treated due to the development of decompensated heart failure within 30 days of their discharge from our hospital. All seven patients stated that they would have originally presented to the emergency department for their symptoms, but consented to alternative treatment by a transitional care physician, or transitionalist. These patients with decompensated heart failure (four male and three female) with a median age of 55 years (24 - 84 years) were evaluated and treated from November 2011 to March 2012. Of the seven patients, four presented with decompensated systolic heart failure (three with diastolic). All seven patients were treated with an intravenous diuretic for hypervolemia in our outpatient infusion room. All of the patients experienced relief of their dyspnea the day of diuretic administration or the following day. No adverse effects or emergency department transfers occurred as a result of outpatient intravenous diuretic therapy. Through the use of outpatient intravenous diuretic therapy, we have avoided the need for emergency department visits and potential hospitalization in select patients with decompensated heart failure. Based on our preliminary findings, the clinical efficacy of this approach to the treatment of heart failure decompensation is not only due to the pharmacologic effectiveness of intravenous diuretics, but also due to the bidirectional open line of communication that exists between transitionalist and patients in the program. The direct telephone access that patients have to the transitionalist allows for close post-hospitalization monitoring and facilitates timely evaluation and treatment when acute issues arise. The added benefit of our particular transitional care program is that we have an alternate venue in the hospital where our transitional care patients can be treated for heart failure decompensation (our outpatient infusion room), thus, enabling us to avoid emergency department transfers and possible hospital admissions. Further investigation of this therapy in a non-emergency department setting is warranted as our experience with this treatment modality is limited to the case series presented.

TBL is customized for individuals who desire a comprehensive approach to improvement of their loose skin. The rate of complications was high and comparable to other published series. There was no difference between the complications of the single-and two-stage patients. While there was an observable reduction in deformity and a high rate of satisfactory aesthetic outcomes, this high number of complications indicates a need to improve clinical performance.

BackgroundDespite a variety of national efforts to improve transitions of care for patients at risk for rehospitalization, 30-day rehospitalization rates for patients with heart failure have remained largely unchanged.MethodsThis is a retrospective review of 73 patients enrolled in our hospital-based, physican-directed Heart Failure Transitional Care Program (HFTCP). This study evaluated the 30- and 90- day readmission rates before and after enrollment in the program. The Transitionalist’s services focused on bedside consultation prior to hospital discharge, follow-up home visits within 72 hours of discharge, frequent follow-up phone calls, disease-specific education, outpatient intravenous diuretic therapy, and around-the-clock telephone access to the Transitionalist.ResultsThe pre-enrollment 30-day readmission rates for acute decompensated heart failure (ADHF) and all-cause readmission was 26.0% and 28.8%, respectively, while the post-enrollment rates for ADHF and all-cause readmission were 4.1% (P < 0.001) and 8.2% (P = 0.002), respectively. The pre-enrollment 90-day all-cause and ADHF readmission rates were 69.8%, and 58.9% respectively, while the post-enrollment rates for all-cause and ADHF were 27.3% (P < 0.001) and 16.4% (P < 0.001) respectively.ConclusionsOur physician-implemented HFTCP reduced rehospitalization risk for patients enrolled in the program. This program may serve as a model to assist other hospital systems to reduce readmission rates of patients with HF.