acase@tulane.edu

acase@tulane.edu

acase@tulane.edu

Hepatitis B virus (HBV) infection is a global leading cause of death as a result of its role in the development of cirrhosis, hepatic decompensation, and hepatocellular carcinoma (HCC). In industrialized nations such as the United States, chronic hepatitis B infection represents a significant and disproportionate disease burden among the foreign-born population. A Markov cohort decision model was developed to determine the cost-effectiveness of HBV screening among new immigrants for the purposes of early detection and treatment, as compared to usual care. The incremental cost-effectiveness ratio for the screening strategy was $45,570 per quality adjusted life year saved. Given the potential for health gains for the immigrant cohort as well as the economic attractiveness of the intervention, some consideration should be given to the addition of a universal HBV screening program to U.S. immigration policy.

Hepatitis B virus (HBV) infection is a global leading cause of death as a result of its role in the development of cirrhosis, hepatic decompensation, and hepatocellular carcinoma (HCC). In industrialized nations such as the United States, chronic hepatitis B infection represents a significant and disproportionate disease burden among the foreign-born population. A Markov cohort decision model was developed to determine the cost-effectiveness of HBV screening among new immigrants for the purposes of early detection and treatment, as compared to usual care. The incremental cost-effectiveness ratio for the screening strategy was $45,570 per quality adjusted life year saved. Given the potential for health gains for the immigrant cohort as well as the economic attractiveness of the intervention, some consideration should be given to the addition of a universal HBV screening program to U.S. immigration policy.

Doctor of Philosophy / Department of Industrial & Manufacturing Systems Engineering / David H. Ben-Arieh / Chih-Hang Wu / Patients who suffer from sepsis or septic shock are of great concern in the healthcare system. Recent data indicate that more than 900,000 severe sepsis or septic shock cases developed in the United States with mortality rates between 20% and 80%. In the United States alone, almost $17 billion is spent each year for the treatment of patients with sepsis. Clinical trials of treatments for sepsis have been extensively studied in the last 30 years, but there is no general agreement of the effectiveness of the proposed treatments for sepsis. Therefore, it is necessary to find accurate and effective tools that can help physicians predict the progression of disease in a patient-specific way, and then provide physicians recommendation on the treatment of sepsis to lower risk for patients dying from sepsis. The goal of this research is to develop a risk assessment tool and a risk management tool for sepsis. In order to achieve this goal, two system dynamic mathematical models (SDMMs) are initially developed to predict dynamic patterns of sepsis progression in innate immunity and adaptive immunity. The two SDMMs are able to identify key indicators and key processes of inflammatory responses to an infection, and a sepsis progression. Second, an integrated-mathematical-multi-agent-based model (IMMABM) is developed to capture the stochastic nature embedded in the development of inflammatory responses to a sepsis. Unlike existing agent-based models, this agent-based model is enhanced by incorporating developed SDMMs and extensive experimental data. With the risk assessment tools, a Markov decision process (MDP) is proposed, as a risk management tool, to apply to clinical decision-makings on sepsis. With extensive computational studies, the major contributions of this research are to firstly develop risk assessment tools to identify the risk of sepsis development during the immune system responding to an infection, and secondly propose a decision-making framework to manage the risk of infected individuals dying from sepsis. The methodology and modeling framework used in this dissertation can be expanded to other disease situations and treatment applications, and have a broad impact to the research area related to computational modeling, biology, medical decision-making, and industrial engineering.

This dissertation consists of two empirical papers and one methods paper. The first two papers use quasi-experimental methods to evaluate the impact of universal health insurance reform in Massachusetts (MA) and Thailand and the third paper evaluates the validity of a quasi-experimental method used in comparative effectiveness research (CER).

Using decision analysis techniques, the cost-effectiveness of two alternatives for treating human poison exposures were modeled. The alternatives were the treatment of poisonings with the services of a regional poison control center versus without access to any poison control center. The relative cost-effectiveness was modeled based on two outcomes (morbidity and mortality) for each of four typical poison exposures: acetaminophen overdose, tricyclic antidepressant overdose, cleaning substance exposure in children, and cough/cold preparation overdose in children. Additionally, analyses were conducted to test the sensitivity of the cost-effectiveness ratio to outcome probability, average inpatient and emergency room charges, and proportion of poison exposures managed on site by the regional poison control center. This research was conducted from society's point of view.

We first studied factors associated with the rate of colonoscopy by primary care physicians (PCPs) in Ontario between the years 1996 and 2005. Next, we conducted an Instrumental Variable Analysis (IVA) to estimate the effect of colonoscopy on colorectal cancer (CRC) incidence and mortality on average-risk subjects aged 50-74 years. Finally, we explored two study cohorts, one by including subjects who had the outcomes during the exposure period (unselected cohort) and the other cohort by excluding those subjects (restricted cohort). We estimated the absolute risk reduction associated with colonoscopy in preventing CRC incidence and mortality using traditional regression analysis, propensity score analysis and IVA. PCPs who were Canadian medical graduates and with more years of experience were more likely to use colonoscopy. PCPs were more likely to use colonoscopy if their patient populations were predominantly women, older, had more illnesses, and if their patients resided in less marginalized neighborhoods (lower unemployment, fewer immigrants, higher income, higher education, and higher English/French fluency). Using PCP rate of discretionary colonoscopy as an instrumental variable, receipt of colonoscopy was associated with a 0.60% absolute reduction in 7-year CRC incidence and a 0.17% absolute reduction in 5-year risk of death due to CRC. The unselected cohort showed an increase in CRC incidence and mortality associated with colonoscopy, whereas the restricted cohort showed a reduction in CRC incidence and mortality associated with colonoscopy. In the restricted cohort, using different statistical models, the absolute risk reduction varied from 0.52-0.60% for CRC incidence and 0.08-0.17% for CRC mortality. There were social disparities in the use of colonoscopy by PCPs and this disparity increased as the overall use of colonoscopy increased over time. Colonoscopy is effective in reducing incidence and mortality due to CRC. Different methods of subject selection and statistical analysis provided different estimates of colonoscopy effectiveness.

We first studied factors associated with the rate of colonoscopy by primary care physicians (PCPs) in Ontario between the years 1996 and 2005. Next, we conducted an Instrumental Variable Analysis (IVA) to estimate the effect of colonoscopy on colorectal cancer (CRC) incidence and mortality on average-risk subjects aged 50-74 years. Finally, we explored two study cohorts, one by including subjects who had the outcomes during the exposure period (unselected cohort) and the other cohort by excluding those subjects (restricted cohort). We estimated the absolute risk reduction associated with colonoscopy in preventing CRC incidence and mortality using traditional regression analysis, propensity score analysis and IVA. PCPs who were Canadian medical graduates and with more years of experience were more likely to use colonoscopy. PCPs were more likely to use colonoscopy if their patient populations were predominantly women, older, had more illnesses, and if their patients resided in less marginalized neighborhoods (lower unemployment, fewer immigrants, higher income, higher education, and higher English/French fluency). Using PCP rate of discretionary colonoscopy as an instrumental variable, receipt of colonoscopy was associated with a 0.60% absolute reduction in 7-year CRC incidence and a 0.17% absolute reduction in 5-year risk of death due to CRC. The unselected cohort showed an increase in CRC incidence and mortality associated with colonoscopy, whereas the restricted cohort showed a reduction in CRC incidence and mortality associated with colonoscopy. In the restricted cohort, using different statistical models, the absolute risk reduction varied from 0.52-0.60% for CRC incidence and 0.08-0.17% for CRC mortality. There were social disparities in the use of colonoscopy by PCPs and this disparity increased as the overall use of colonoscopy increased over time. Colonoscopy is effective in reducing incidence and mortality due to CRC. Different methods of subject selection and statistical analysis provided different estimates of colonoscopy effectiveness.