T2DM Clinical Decision Support System: Comprehensive Patient Care

We report on the current state of type 2 diabetes clinical decision support systems (CDSS), identify gaps that contribute to the lack of CDSS success, and apply lessons learned from practice for developing and implementing a localized diabetes CDSS. A survey of the literature reveals mixed findings regarding the efficacy of the CDSS; they do not include patient-rich information – the patient experience data in the electronic health records. We believe that diabetes care can improve by guiding clinical decisions using published evidence, patient preferences, and clinical data augmented by the local patient experience and social determinants of health using natural language processing and machine learning techniques

Valuation of scleroderma and psoriatic arthritis health states by the general public

<p>Abstract</p> <p>Objective</p> <p>Psoriatic arthritis (PsA) and scleroderma (SSc) are chronic rheumatic disorders with detrimental effects on health-related quality of life. Our objective was to assess health values (utilities) from the general public for health states common to people with PsA and SSc for economic evaluations.</p> <p>Methods</p> <p>Adult subjects from the general population in a Midwestern city (N = 218) completed the SF-12 Health Survey and computer-assisted 0-100 rating scale (RS), time trade-off (TTO, range: 0.0-1.0) and standard gamble (SG, range: 0.0-1.0) utility assessments for several hypothetical PsA and SSc health states.</p> <p>Results</p> <p>Subjects included 135 (62%) females, 143 (66%) Caucasians, and 62 (28%) African-Americans. The mean (SD) scores for the SF-12 Physical Component Summary scale were 52.9 (8.3) and for the SF-12 Mental Component Summary scale were 49.0 (9.1), close to population norms. The mean RS, TTO, and SG scores for PsA health states varied with severity, ranging from 20.2 to 63.7 (14.4-20.3) for the RS 0.29 to 0.78 (0.24-0.31) for the TTO, and 0.48 to 0.82 (0.24-0.34) for the SG. The mean RS, TTO, and SG scores for SSc health states were 25.3-69.7 (15.2-16.3) for the RS, 0.36-0.80 (0.25-0.31) for the TTO, and 0.50-0.81 (0.26-0.32) for the SG, depending on disease severity.</p> <p>Conclusion</p> <p>Health utilities for PsA and SSc health states as assessed from the general public reflect the severity of the diseases. These descriptive findings could have implications regarding comparative effectiveness research for tests and treatments for PsA and SSc.</p

Evaluating patient values and preferences for thromboprophylaxis decision making during pregnancy: a study protocol

Peer reviewe

Cost effectiveness of recombinant factor VIIa for treatment of intracerebral hemorrhage

<p>Abstract</p> <p>Background</p> <p>Phase I/II placebo-controlled clinical trials of recombinant Factor VIIa (rFVIIa) suggested that administration of rFVIIa within 4 hours after onset of intracerebral hemorrhage (ICH) is safe, limits ICH growth, and improves outcomes. We sought to determine the cost-effectiveness of rFVIIa for acute ICH treatment, using published Phase II data. We hypothesized that rFVIIa would have a low marginal cost-effectiveness ratio (mCER) given the poor neurologic outcomes after ICH with conventional management.</p> <p>Methods</p> <p>We performed an incremental cost-effectiveness analysis from the societal perspective, considering conventional management vs. 80 ug/kg rFVIIa treatment for acute ICH cases meeting Phase II inclusion criteria. The time frame for the analysis was 1. 25 years: data from the Phase II trial was used for 90 day outcomes and rFVIIa complications – arterial thromboembolic events (ATE). We assumed no substantial cost differences in care between the two strategies except: 1) cost of rFVIIa (for an 80 mcg/kg dose in an 80 kg patient, assumed cost of $6,408); 2) cost of ATE side effects from rFVIIa (which also decrease quality of life and increase the chance of death); and 3) differential monetary costs of outcomes and their impact on quality of life, including disposition (home vs. nursing home), and outpatient vs. inpatient rehabilitation. Sensitivity analyses were performed to explore uncertainty in parameter estimates, impact of rFVIIa cost, direct cost of neurologic outcomes, probability of ATE, and outcomes after ATE.</p> <p>Results</p> <p>In the "base case", treating ICH with rFVIIa dominates the usual care strategy by being more effective and less costly. rFVIIa maintained a mCER <$50,000/QALY over a wide range of sensitivity analyses. Sensitivity analyses showed that the cost of rFVIIa must exceed $14,500, or the frequency of ATE exceed 29$50,000/QALY. Varying the cost and/or reducing the utility of health states following ATE did not impact results.</p> <p>Conclusion</p> <p>Based on data from preliminary trials, treating selected ICH patients with rFVIIa results in lower cost and improved clinical outcomes. This potential cost-effectiveness must be considered in light of the Phase III trial results.</p

Biophysical and Functional Characterization of Rhesus Macaque IgG Subclasses

Antibodies raised in Indian rhesus macaques [Macaca mulatta (MM)] in many preclinical vaccine studies are often evaluated in vitro for titer, antigen-recognition breadth, neu- tralization potency, and/or effector function, and in vivo for potential associations with protection. However, despite reliance on this key animal model in translation of promising candidate vaccines for evaluation in first in man studies, little is known about the proper- ties of MM immunoglobulin G (IgG) subclasses and how they may compare to human IgG subclasses. Here, we evaluate the binding of MM IgG1, IgG2, IgG3, and IgG4 to human Fc gamma receptors (FcγR) and their ability to elicit the effector functions of human FcγR-bearing cells, and unlike in humans, find a notable absence of subclasses with dramatically silent Fc regions. Biophysical, in vitro, and in vivo characterization revealed MM IgG1 exhibited the greatest effector function activity followed by IgG2 and then IgG3/4. These findings in rhesus are in contrast with the canonical understanding that IgG1 and IgG3 dominate effector function in humans, indicating that subclass-switching profiles observed in rhesus studies may not strictly recapitulate those observed in human vaccine studies

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts