A Process Improvement Study on a Military System of Clinics to Manage Patient Demand and Resource Utilization Using Discrete-Event Simulation, Sensitivity Analysis, and Cost-Benefit Analysis

Inefficiencies in the healthcare system are a growing concern. Long wait-times are a concern at military clinics because it takes servicemembers away from performing their duties. Managing wait-times are particularly challenging due to frequent relocations of servicemembers and variable patient demands that are less likely to be experienced by civilian clinics. Military clinics must be capable to meet increasing demand when servicemembers require a Deployment Health Assessment; it also needs to be capable of handling an instantaneous surge of walk-ins when a medical incident occurs in the local area. It must be able to meet these demands in a fiscally austere environment. Existing research primarily focuses on stand-alone clinics, whereas this research takes a novel approach of examining a system of clinics, in which some resources are shared. This research evaluates the impacts of variable staffing levels on total wait-time for the system of clinics at baseline demand and when demand increases, using discrete-event simulation, sensitivity analysis, and cost-benefit analysis. This research finds misallocated resources; the wait-time of alternative systems are sensitive to deployment and medical incident demands; and hiring an optometrist while removing an occupational medicine doctor provides the highest savings in baseline, deployment, and medical incident demand environments

An Allosteric Anti-tryptase Antibody for the Treatment of Mast Cell-Mediated Severe Asthma

Severe asthma patients with low type 2 inflammation derive less clinical benefit from therapies targeting type 2 cytokines and represent an unmet need. We show that mast cell tryptase is elevated in severe asthma patients independent of type 2 biomarker status. Active β-tryptase allele count correlates with blood tryptase levels, and asthma patients carrying more active alleles benefit less from anti-IgE treatment. We generated a noncompetitive inhibitory antibody against human β-tryptase, which dissociates active tetramers into inactive monomers. A 2.15 Å crystal structure of a β-tryptase/antibody complex coupled with biochemical studies reveal the molecular basis for allosteric destabilization of small and large interfaces required for tetramerization. This anti-tryptase antibody potently blocks tryptase enzymatic activity in a humanized mouse model, reducing IgE-mediated systemic anaphylaxis, and inhibits airway tryptase in Ascaris-sensitized cynomolgus monkeys with favorable pharmacokinetics. These data provide a foundation for developing anti-tryptase as a clinical therapy for severe asthma