Using an agent-based model to analyze the dynamic communication network of the immune response.

BACKGROUND: The immune system behaves like a complex, dynamic network with interacting elements including leukocytes, cytokines, and chemokines. While the immune system is broadly distributed, leukocytes must communicate effectively to respond to a pathological challenge. The Basic Immune Simulator 2010 contains agents representing leukocytes and tissue cells, signals representing cytokines, chemokines, and pathogens, and virtual spaces representing organ tissue, lymphoid tissue, and blood. Agents interact dynamically in the compartments in response to infection of the virtual tissue. Agent behavior is imposed by logical rules derived from the scientific literature. The model captured the agent-to-agent contact history, and from this the network topology and the interactions resulting in successful versus failed viral clearance were identified. This model served to integrate existing knowledge and allowed us to examine the immune response from a novel perspective directed at exploiting complex dynamics, ultimately for the design of therapeutic interventions. RESULTS: Analyzing the evolution of agent-agent interactions at incremental time points from identical initial conditions revealed novel features of immune communication associated with successful and failed outcomes. There were fewer contacts between agents for simulations ending in viral elimination (win) versus persistent infection (loss), due to the removal of infected agents. However, early cellular interactions preceded successful clearance of infection. Specifically, more Dendritic Agent interactions with TCell and BCell Agents, and more BCell Agent interactions with TCell Agents early in the simulation were associated with the immune win outcome. The Dendritic Agents greatly influenced the outcome, confirming them as hub agents of the immune network. In addition, unexpectedly high frequencies of Dendritic Agent-self interactions occurred in the lymphoid compartment late in the loss outcomes. CONCLUSIONS: An agent-based model capturing several key aspects of complex system dynamics was used to study the emergent properties of the immune response to viral infection. Specific patterns of interactions between leukocyte agents occurring early in the response significantly improved outcome. More interactions at later stages correlated with persistent inflammation and infection. These simulation experiments highlight the importance of commonly overlooked aspects of the immune response and provide insight into these processes at a resolution level exceeding the capabilities of current laboratory technologies.

Benefits of monitoring patients with mobile cardiac telemetry (MCT) compared with the Event or Holter monitors.

INTRODUCTION: This research is meant to establish if a patient monitored with mobile cardiac telemetry (MCT) sees different outcomes regarding diagnostic yield of arrhythmia, therapeutic management through the use of antiarrhythmic drugs, and cardiovascular costs incurred in the hospital setting when compared with more traditional monitoring devices, such as the Holter or the Event monitor. MATERIALS AND METHODS: We conducted a retrospective analysis spanning 57 months of claims data from January 2007 to September 2011 pertaining to 200,000+ patients, of whom 14,000 used MCT only, 54,000 an Event monitor only, and 163,000 a Holter monitor only. Those claims came from the Truven database, an employer database that counts 2.8 million cardiovascular patients from an insured population of about 10 million members. We employed a pair-wise pre/post test-control methodology, and ensured that control patients were similar to test patients along the following dimensions: age, geographic location, type of cardiovascular diagnosis both in the inpatient and outpatient settings, and the cardiovascular drug class the patient uses. RESULTS: First, the diagnostic yield of patients monitored with MCT is 61%, that is significantly higher than that of patients that use the Event monitor (23%) or the Holter monitor (24%). Second, patients naive to antiarrhythmic drugs initiate drug therapy after monitoring at the following rates: 61% for patients that use MCT compared with 39% for patients that use the Event and 43% for patients that use the Holter. Third, there are very significant inpatient cardiovascular savings (in the tens of thousands of dollars) for patients that undergo ablation, coronary artery bypass graft (CABG) and valve septa. Savings are more modest but nonetheless significant when it comes to the heart/pericardium procedure. CONCLUSION: Given the superior outcome of MCT regarding both patient care and hospital savings, hospitals only stand to gain by enforcing protocols that favor the MCT system over the Event or the Holter monitor.