All Publications


  • Operative Versus Nonoperative Management of Appendicitis: A Long-Term Cost Effectiveness Analysis. MDM policy & practice Sceats, L. A., Ku, S., Coughran, A., Barnes, B., Grimm, E., Muffly, M., Spain, D. A., Kin, C., Owens, D. K., Goldhaber-Fiebert, J. D. 2019; 4 (2): 2381468319866448

    Abstract

    Background. Recent clinical trials suggest that nonoperative management (NOM) of patients with acute, uncomplicated appendicitis is an acceptable alternative to surgery. However, limited data exist comparing the long-term cost-effectiveness of nonoperative treatment strategies. Design. We constructed a Markov model comparing the cost-effectiveness of three treatment strategies for uncomplicated appendicitis: 1) laparoscopic appendectomy, 2) inpatient NOM, and 3) outpatient NOM. The model assessed lifetime costs and outcomes from a third-party payer perspective. The preferred strategy was the one yielding the greatest utility without exceeding a $50,000 willingness-to-pay threshold. Results. Outpatient NOM cost $233,700 over a lifetime; laparoscopic appendectomy cost $2500 more while inpatient NOM cost $7300 more. Outpatient NOM generated 24.9270 quality-adjusted life-years (QALYs), while laparoscopic appendectomy and inpatient NOM yielded 0.0709 and 0.0005 additional QALYs, respectively. Laparoscopic appendectomy was cost-effective compared with outpatient NOM (incremental cost-effectiveness ratio $32,300 per QALY gained); inpatient NOM was dominated by laparoscopic appendectomy. In one-way sensitivity analyses, the preferred strategy changed when varying perioperative mortality, probability of appendiceal malignancy or recurrent appendicitis after NOM, probability of a complicated recurrence, and appendectomy cost. A two-way sensitivity analysis showed that the rates of NOM failure and appendicitis recurrence described in randomized trials exceeded the values required for NOM to be preferred. Limitations. There are limited NOM data to generate long-term model probabilities. Health state utilities were often drawn from single studies and may significantly influence model outcomes. Conclusion. Laparoscopic appendectomy is a cost-effective treatment for acute uncomplicated appendicitis over a lifetime time horizon. Inpatient NOM was never the preferred strategy in the scenarios considered here. These results emphasize the importance of considering long-term costs and outcomes when evaluating NOM.

    View details for DOI 10.1177/2381468319866448

    View details for PubMedID 31453362

  • Cost-effectiveness of Canakinumab for Prevention of Recurrent Cardiovascular Events. JAMA cardiology Sehested, T. S., Bjerre, J., Ku, S., Chang, A., Jahansouz, A., Owens, D. K., Hlatky, M. A., Goldhaber-Fiebert, J. D. 2019

    Abstract

    Importance: In the Canakinumab Anti-inflammatory Thrombosis Outcome Study (CANTOS) trial, the anti-inflammatory monoclonal antibody canakinumab significantly reduced the risk of recurrent cardiovascular events in patients with previous myocardial infarction (MI) and high-sensitivity C-reactive protein (hs-CRP) levels of 2 mg/L or greater.Objective: To estimate the cost-effectiveness of adding canakinumab to standard of care for the secondary prevention of major cardiovascular events over a range of potential prices.Design, Setting, and Participants: A state-transition Markov model was constructed to estimate costs and outcomes over a lifetime horizon by projecting rates of recurrent MI, coronary revascularization, infection, and lung cancer with and without canakinumab treatment. We used a US health care sector perspective, and the base case used the current US market price of canakinumab of $73 000 per year. A hypothetical cohort of patients after MI aged 61 years with an hs-CRP level of 2 mg/L or greater was constructed.Interventions: Canakinumab, 150 mg, administered every 3 months plus standard of care compared with standard of care alone.Main Outcomes and Measures: Lifetime costs and quality-adjusted life-years (QALYs), discounted at 3% annually.Results: Adding canakinumab to standard of care increased life expectancy from 11.31 to 11.36 years, QALYs from 9.37 to 9.50, and costs from $242 000 to $1 074 000, yielding an incremental cost-effectiveness ratio of $6.4 million per QALY gained. The price would have to be reduced by more than 98% (to $1150 per year or less) to meet the $100 000 per QALY willingness-to-pay threshold. These results were generally robust across alternative assumptions, eg, substantially lower health-related quality of life after recurrent cardiovascular events, lower infection rates while receiving canakinumab, and reduced all-cause mortality while receiving canakinumab. Including a potential beneficial effect of canakinumab on lung cancer incidence improved the incremental cost-effectiveness ratio to $3.5 million per QALY gained. A strategy of continuing canakinumab selectively in patients with reduction in hs-CRP levels to less than 2 mg/L would have a cost-effectiveness ratio of $819 000 per QALY gained.Conclusions and Relevance: Canakinumab is not cost-effective at current US prices for prevention of recurrent cardiovascular events in patients with a prior MI. Substantial price reductions would be needed for canakinumab to be considered cost-effective.

    View details for PubMedID 30649147

  • Use of gasotransmitters for the controlled release of polymer-based nitric oxide carriers in medical applications JOURNAL OF CONTROLLED RELEASE Yang, C., Jeong, S., Ku, S., Lee, K., Park, M. 2018; 279: 157–70

    Abstract

    Nitric Oxide (NO) is a small molecule gasotransmitter synthesized by nitric oxide synthase in almost all types of mammalian cells. NO is synthesized by NO synthase by conversion of l-arginine to l-citrulline in the human body. NO then stimulates soluble guanylate cyclase, from which various physiological functions are mediated in a concentration-dependent manner. High concentrations of NO induce apoptosis or antibacterial responses whereas low NO circulation leads to angiogenesis. The bidirectional effect of NO has attracted considerable attention, and efforts to deliver NO in a controlled manner, especially through polymeric carriers, has been the topic of much research. This naturally produced signaling molecule has stood out as a potentially more potent therapeutic agent compared to exogenously synthesized drugs. In this review, we will focus on past efforts of using the controlled release of NO via polymer-based materials to derive specific therapeutic results. We have also added studies and our future suggestions on co-delivery methods with other gasotransmitters as a step towards developing multifunctional carriers.

    View details for PubMedID 29673643