Clinical decision support capabilities of commercially-available clinical information systems.

BACKGROUND: The most effective decision support systems are integrated with clinical information systems, such as inpatient and outpatient electronic health records (EHRs) and computerized provider order entry (CPOE) systems. Purpose The goal of this project was to describe and quantify the results of a study of decision support capabilities in Certification Commission for Health Information Technology (CCHIT) certified electronic health record systems. METHODS: The authors conducted a series of interviews with representatives of nine commercially available clinical information systems, evaluating their capabilities against 42 different clinical decision support features. RESULTS: Six of the nine reviewed systems offered all the applicable event-driven, action-oriented, real-time clinical decision support triggers required for initiating clinical decision support interventions. Five of the nine systems could access all the patient-specific data items identified as necessary. Six of the nine systems supported all the intervention types identified as necessary to allow clinical information systems to tailor their interventions based on the severity of the clinical situation and the user's workflow. Only one system supported all the offered choices identified as key to allowing physicians to take action directly from within the alert. Discussion The principal finding relates to system-by-system variability. The best system in our analysis had only a single missing feature (from 42 total) while the worst had eighteen.This dramatic variability in CDS capability among commercially available systems was unexpected and is a cause for concern. CONCLUSIONS: These findings have implications for four distinct constituencies: purchasers of clinical information systems, developers of clinical decision support, vendors of clinical information systems and certification bodies.

PIM KINASE INHIBITION: SINGLE AGENT AND COMBINATION APPROACHES IN B-CELL LYMPHOMA

Proviral integration site for Moloney murine leukemia virus (Pim) kinases are Ser/Thr/Tyr kinases. They modulate B-cell development but become oncoproteins and promote cancer development once overexpressed. Containing three isoforms, Pim-1, -2 and -3 are known to phosphorylate various substrates that regulate transcription, translation, cell cycle, and survival pathways in both hematological and solid tumors. Mantle cell lymphoma (MCL) is an aggressive B-cell lymphoma. Elevated Pim kinase levels are common in MCL, and it negatively correlates with patient outcome. SGI-1776 is a small molecule inhibitor selective for Pim-1/-3. We hypothesize that SGI-1776 treatment in MCL will inhibit Pim kinase function, and inhibition of downstream substrates phosphorylation will disrupt transcriptional, translational, and cell cycle processes while promoting apoptosis. SGI-1776 treatment induced moderate to high levels of apoptosis in four MCL cell lines (JeKo-1, Mino, SP-53 and Granta-519) and peripheral blood mononuclear cells (PBMCs) from MCL patients. Phosphorylation of transcription and translation regulators, c-Myc and 4E-BP1 declined in both model systems. Additionally, levels of short-lived Mcl-1 mRNA and protein also decreased and correlated with decline of global RNA synthesis. Collectively, our investigations highlight Pim kinases as viable drug targets in MCL and emphasize their roles in transcriptional and translational regulation. We further investigated a combination strategy using SGI-1776 with bendamustine, an FDA-approved DNA-damaging alkylating agent for treating non-Hodgkin’s lymphoma. We hypothesized this combination will enhance SGI-1776-induced transcription and translation inhibition, while promoting bendamustine-triggered DNA damage and inducing additive to synergistic cytotoxicity in B-cell lymphoma. Bendamustine alone resulted in moderate levels of apoptosis induction in MCL cell lines (JeKo-1 and Mino), and in MCL and splenic marginal zone lymphoma (a type of B-cell lymphoma) primary cells. An additive effect in cell killing was observed when combined with SGI-1776. Expectedly, SGI-1776 effectively decreased global RNA and protein synthesis levels, while bendamustine significantly inhibited DNA synthesis and generated DNA damage response. In combination, intensified inhibitory effects in DNA, RNA and protein syntheses were observed. Together, these data suggested feasibility of using Pim kinase inhibitor in combination with chemotherapeutic agents such as bendamustine in B-cell lymphoma, and provided foundation of their mechanism of actions in lymphoma cells.