Opioid Use Disorder is defined by the NIH as “the chronic use of opioids that causes clinically significant distress or impairment.”1 Due to a number of factors, the overuse of opioids has become an epidemic in the United States. In recent years there have been a number of lawsuits against pharmaceutical companies and other parties who have benefitted from the proliferation of this issue. In most cases, it is up to the states or local governments who receive these funds to determine their best use. The purpose of this Thesis is to analyze the resources recommended by Ballad Health’s Community Health Needs Assessments, and five additional panels of experts in this field, and to compare these recommendations with available resources, along with making recommendations for the distribution and use of funds coming from a number of lawsuits and settlements.

Background: The mood stabilizer lithium has long been reported to be associated with reduced suicide risks, but many studies reporting associations between lithium and reduced suicide risks also have been nonrandomized and lacked adjustment for many potential confounders, active controls, uniform follow-up, or intent-to-treat samples. Concerns also have been raised that medications being considered as potential suicide preventative might increase risks of nonsuicide mortality while reducing risks of suicide. Methods: Three studies of Veterans Health Administration (VHA) patients were conducted combining high-dimensional propensity score matching with intent-to-treat analyses to examine the associations between lithium and valproate and one-year suicide and nonsuicide mortality outcomes. Results: In intention-to-treat analyses, initiation of lithium, compared to valproate, was associated with increased suicide mortality over 0-365 days among patients with bipolar disorder (Hazard Ratio (HR) 1.50 [95% Confidence Interval 1.05, 2.15]) Nonsuicide mortality among VHA patients with or without bipolar disorder was not significantly associated with the initiation of lithium compared to valproate ( HR 0.92 [0.82-1.04]). Rates of treatment discontinuation, however, were very high (≈ 92%). Longitudinal analyses revealed that the increased suicide risks associated with initiating lithium among patients with bipolar disorder occurred exclusively after discontinuation of lithium vii treatment. In secondary analyses restricted to patients still receiving their initial treatment, there was no difference in suicide risk between the initiation of lithium or valproate. Conclusions: Significantly increased risks of suicide were observed at one year among VHA patients with bipolar disorder initiating lithium compared to valproate, related to risks observed after the discontinuation of lithium treatment Since these studies are nonrandomized, confounding may account for some or all of our findings, including the risks observed after lithium discontinuation. Nevertheless, these results suggest that health systems and providers consider steps to minimize any potential lithium discontinuation-associated risk. Approaches might include educating patients about possible risks associated with discontinuation and closely monitoring patients after discontinuation if feasible. Given the obvious importance of any substantive difference between lithium and valproate in suicide or nonsuicide mortality risk, our studies also suggest that further research is needed, especially research that can further minimize the potential for confounding.

Background: Recent national trends and distribution of ileal pouch-anal anastomosis (IPAA) procedures for patients with ulcerative colitis (UC) are unknown. We examined the frequency of use of elective IPAA procedures among patients with UC and the distribution of IPAA procedures across more than 140 U.S. academic medical centers and their affiliates. Methods: Data were obtained from the University HealthSystem Consortium for patients with a primary diagnosis of UC admitted electively between 2012 and 2015. Results: The mean age of the study population (n=6,875) was 43 years and 57% were men. Among these, one-third (n=2,307) underwent an IPAA, while two-thirds (n=4,568) underwent colectomy, proctectomy, proctocolectomy or other procedures. The proportion of IPAA cases among all elective admissions was relatively stable at 33-35% during the years under study. A total of 131 hospitals, out of 279 hospitals participating in the UHC, performed IPAA. The median number of IPAA cases performed annually was 1.9 [IQR 0.8 – 4.3]. Nearly one half (48%) of these cases were performed by the top ten hospitals. Overall, only a total of 30 centers performed ³ five elective IPAA cases annually. Conclusions: Although the frequency of elective IPAA surgery in recent years has been stable, nearly one half of all IPAA cases was performed at ten hospitals. The concentration of IPAA cases at high-volume centers, and the steady number of cases performed annually, have potential implications for fellowship training, patient clinical outcomes and access to care.

Background: Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality in the U.S. Acute myocardial infarction (AMI), with or without ST-segment elevation, is a common presentation of coronary heart disease and affected more than 800,000 American adults in 2010. The overall goal of this dissertation was to examine decade-long trends in the extent of delay in the receipt of a primary percutaneous coronary intervention (PCI) among patients hospitalized with ST-segment elevation myocardial infarction (STEMI), 30-day hospital readmission rates in patients having survived an AMI, and multiple decade long trends in 1-year post-hospital all-cause mortality, as well as factors associated with these outcomes, among patients hospitalized with AMI. Methods: Data from the Worcester Heart Attack Study, a population-based chronic disease surveillance project that has been carried out among adult residents of the Worcester, MA, metropolitan area, hospitalized with AMI on a biennial basis from 1975 through 2009 at all medical centers in central MA, were used for this dissertation. Results: Between 1999 and 2009, among patients hospitalized with STEMI, the likelihood of receiving a primary PCI within 90 minutes after emergency department arrival increased dramatically from 1999/2001 (11.6%) to 2007/2009 (70.5%). Between 1999 and 2009, among hospital survivors of an AMI, the 30-day all-cause rehospitalization rates decreased from 1999/2001 (20.3%) to 2007/2009 (16.7%). The overall cause-specific 30-day rehospitalization rates due to CVD, non-CVD, and AMI were 10.1%, 7.1%, and 1.8%, respectively, during the years under study. Between 1975 and 2009, among hospital survivors for a first AMI, the 1-year post-discharge mortality rates remained relatively stable from 1975-1984 (12.9%) to 1986-1997 (12.5%), but increased during 1999-2009 (15.8%). We identified several demographic, clinical and in-hospital treatment factors associated with an increased risk of failing to receive a primary PCI within 90 minutes after emergency department arrival, 30-day readmissions, and 1-year post-discharge mortality. Conclusions: Our findings can hopefully lead to the enhanced development of innovative, patient-centered, intervention strategies which can further improve the treatment and transitions of care, as well as short and long-term prognosis, of men and women hospitalized with AMI.

Background: Treatment decisions for elderly patients with gallbladder pathology are complex. Little is known about what factors go into treatment decisions in this population. We used Medicare data to examine gender-based differences in the use of cholecystectomy vs. cholecystostomy tube placement in elderly patients with acute cholecystitis. Methods: We queried a 5% random sample of Medicare data (2009-2011) for patients >65 admitted for acute cholecystitis (by ICD-9 code) who subsequently underwent a cholecystectomy and/or cholecystostomy tube placement. Demographic information (age, race), clinical characteristics (Elixhauser index, presence of biliary pathology), and hospital outcomes (case fatality rate, length of stay, need for ICU care) were compared by gender. A multivariable model was used to examine predictors of cholecystectomy vs. cholecystostomy tube placement. Results: Of 4063 patients admitted with cholecystitis undergoing the procedures of interest just over half (58%) were women. The majority of patients (93%) underwent cholecystectomy. Compared to women, men were younger (average age 76 vs. 78, p value < 0.01) and had few comorbidities (average Elixhauser 1.2 vs. 1.4 p value < 0.01). Case fatality rate was similar between men (2.5%) and women (2.4% p value 0.48). A higher percentage of men spent time in the ICU (36%) compared to women (31% p value < 0.01). On multivariable analysis men were 30% less likely to undergo cholecystectomy (OR 0.69, 95% CI 0.53-0.91). Conclusion: Elderly men are less likely than elderly women to undergo cholecystectomy for acute cholecystitis despite being younger with less co morbidity and are more likely to spend time in the ICU. More research is needed to determine whether a difference in treatment is contributing to the higher rate of ICU utilization in elderly men with acute cholecystitis.

In recent years, the transplant community has explored and adopted tools for quantifying clinical insight into illness severity and frailty. This dissertation work explores the interplay between objective and subjective assessments of physical health status and the implications for liver transplant candidate and recipient outcomes. The first aim characterizes national epidemiologic trends and the impact of Centers for Medicare and Medicaid quality improvement policies on likelihood of waitlist removal based on the patient being too frail to benefit from liver transplant (“too sick to transplant”). This aim includes more than a decade (2002–2012) of comprehensive national transplant waitlist data (Scientific Registry of Transplant Recipients (SRTR)). The second aim will assess and define objective parameters of liver transplant patient frailty by measuring decline in lean core muscle mass (“sarcopenia”) using abdominal CT scans collected retrospectively at a single U.S. transplant center between 2006 and 2015. The relationship between these objective sarcopenia measures and subjective functional status assessed using the Karnofsky Functional Performance (KPS) scale are described and quantified. The third aim quantifies the extent to which poor functional status (KPS) pre-transplant is associated with worse post-transplant survival and includes national data on liver transplantations conducted between 2005 and 2014 (SRTR). The results of this dissertation will help providers in the assessment of frailty and subsequent risk of adverse outcomes and has implications for strategic clinical management in anticipation of surgery. This research will also to serve to inform national policy on the design of transplant center performance measures.

Background: Racial and ethnic minorities are under-represented participants in health-related research. Comprehension and understanding of the research process are a barrier to research participation. A potential approach to engaging underserved populations in research is through improving research literacy, which we define as “the capacity to obtain, process and understand basic information needed to make informed decisions about research participation.” Methods: Through primary data collection and mixed-methods approaches, this doctoral thesis seeks to: 1) define and conceptualize the domains, determinants, and impacts of research literacy through the development of a multi-component comprehensive framework, 2) operationalize research literacy by developing and psychometrically testing the Research Literacy Scale, and 3) quantify differences in research literacy, measured by the Research Literacy Scale, by race/ethnicity, race-related factors, and other socio-demographic factors. Results: We created a framework outlining eight domains of research literacy and multi-faceted influences of societal, community, researcher, and participant factors that may influence an individual’s level of research literacy. The Research Literacy Scale created is comprised of 16 items, with a KR-20 estimate of 0.81 and test-retest reliability of 0.84. We found differences in mean scale scores by race/ethnicity, age, education, income, and health literacy (all p < 0.01). African-Americans and Latinos have lower research literacy scores, as compared to non-Latino Whites. Race-consciousness was associated with research literacy score. Conclusions: This study is the first to define, assess, and quantify factors associated with research literacy in a diverse community sample and may provide insights on approaches to enhance minority engagement in health-related research.

An emerging framework, the Identity Pathology (IP) model, partially addresses persistent uncertainties about the primary causes of disparities in cardiovascular health (CVH) between black and white women and men through outlining how identity beliefs associated with social group membership lead to predictable differences in the health-damaging effects of discrimination exposure. Using data from the CARDIA cohort, this doctoral thesis seeks to: 1) propose a novel psychosocial characteristic, identity pathology, that drives the distribution of reported race and gender discrimination in health-relevant ways, 2) assess whether there are group differences in the effects of multiple versus single forms of discrimination on future CVH, and 3) assess variation between these groups in the relationships of reported racial and gender discrimination in a variety of daily life settings with future CVH. The IP framework suggests that beliefs about identity unique to each gendered race group influence the perception of discrimination and whether reported exposure will be associated with CVH. Simultaneous reports of racial and gender discrimination in multiple settings (compared with no discrimination) were negatively associated with future CVH only among white men. Further, the setting in which discrimination was reported appeared to be a significant indicator of whether experiencing multiple forms of discrimination negatively impacted CVH in each group. Our findings contribute to the literature through introducing a novel framework for assessing the effects of interpersonal discrimination. This work also provides preliminary evidence that compounded experiences of interpersonal racial and gender discrimination may not substantially contribute to poorer CVH among black women.

Background. Diabetes requires significant disease management, patient-provider communication, and interaction between patients, family members, caregivers, and care teams. Emerging patient-facing technologies, such as cellular-enabled glucose meters, can facilitate additional care support and improve diabetes self-management. This study evaluated patient acceptability, feasibility, and efficacy of a diabetes care support program facilitated by cellular-enabled glucose meters. Methods. A two-phase study approach was taken. Get In Touch – Phase 1 (GIT-1) was a 1-month pilot involving patients with type 1 and type 2 diabetes. Get In Touch – Phase 2 (GIT-2) was a 12-month randomized controlled crossover trial involving patients with poorly-controlled type 2 diabetes. Results from GIT-1 and preliminary results from GIT-2 are presented. Results. GIT-1 participants with type 1 (n=6) and type 2 (n=10) diabetes reported the intervention and cellular-enabled glucose meter were easy to use and useful while identifying potential areas of improvement. GIT-2 participants in both the intervention (n=60) and control (n=60) groups saw significant improvements in treatment satisfaction and A1c change, with intervention participants experiencing slightly greater improvements in each after 6 months (p=0.09 and p=0.16, respectively) compared to control participants. Conclusions. Patients reported favorable acceptability of the intervention. Preliminary results from a randomized trial demonstrated potential of intervention to improve patient-reported and physiological health outcomes. Future studies should evaluate feasibility and efficacy over a longer period of time, with a greater number of participants, and targeting different populations of patients with diabetes. Provider perspectives and changes in provider behavior, clinical work flow, and caregiver burden should also be assessed.

Background: Overtreatment of localized prostate cancer (PCa) is a concern as many men die of other causes prior to experiencing a treatment benefit. This dissertation characterizes the need for assessing other cause mortality (OCM) risk in older men with PCa and informs efforts to identify patients most likely to benefit from definitive PCa treatment. Methods: Using the linked Surveillance Epidemiology and End Results-Medicare Health Outcomes Survey database, 2,931 men (mean age=75) newly diagnosed with clinical stage T1a-T3a PCa from 1998-2009 were identified. Survival analysis methods were used to compare observed 10-year OCM by primary treatment type. Age and health factors predictive of primary treatment type were assessed with multinomial logistic regression. Predicted mortality estimates from Social Security life tables (recommended for life expectancy evaluation) and two OCM risk estimation tools were compared to observed rates. An improved OCM prediction model was developed fitting Fine and Gray competing risks models for 10-year OCM with age, sociodemographic, comorbidity, activities of daily living, and patient-reported health data as predictors. The tools’ ability to discriminate between patients who died and those who did not was evaluated with Harrell’s c-index (range 0.5-1), which also guided new model selection. Results: Fifty-four percent of older men with localized PCa underwent radiotherapy while 13% underwent prostatectomy. Twenty-three percent of those treated with radiotherapy and 12% of those undergoing prostatectomy experienced OCM within 10 years of treatment and thus were considered overtreated. Health factors indicative of a shorter life expectancy (increased comorbidity, worse physical health, smoking) had little to no association with radiotherapy assignment but were significantly related to reductions in the likelihood of undergoing prostatectomy. Social Security life tables overestimated mortality risk and discriminated poorly between men who died and those who did not over 10 years (c-index=0.59). Existing OCM risk estimation tools were less likely to overestimate OCM rates and had limited but improved discrimination (c-index=0.64). A risk model developed with self-reported age, Charlson comorbidity index score, overall health (excellent-good/fair/poor), smoking, and marital status predictors had improved discrimination (c-index=0.70). Conclusions: Overtreatment of older men with PCa is primarily attributable to radiotherapy and may be reduced by pretreatment assessment of mortality-related health factors. This dissertation provides a prognostic model which utilizes a set of five self-reported characteristics that better identify patients likely to die of OCM within 10 years of diagnosis than age and comorbidity-based assessments alone.