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Item Associations of opioid prescription dose and discontinuation with risk of substance-related morbidity in long-term opioid therapy(Wolters Kluwer, 2022) Quinn, Patrick D.; Chang, Zheng; Bair, Matthew J.; Rickert, Martin E.; Gibbons, Robert D.; Kroenke, Kurt; D’Onofrio, Brian M.; Medicine, School of MedicineEfforts to reduce opioid-related harms have decreased opioid prescription but have provoked concerns about unintended consequences, particularly for long-term opioid therapy (LtOT) recipients. Research is needed to address the knowledge gap regarding how risk of substance-related morbidity changes across LtOT and its discontinuation. This study used nationwide commercial insurance claims data and a within-individual design to examine associations of LtOT dose and discontinuation with substance-related morbidity. We identified 194,839 adolescents and adults who initiated opioid prescription in 2010 to 2018 and subsequently received LtOT. The cohort was followed for a median of 965 days (interquartile range, 525-1550), of which a median of 176 days (119-332) were covered by opioid prescription. During follow-up, there were 17,582 acute substance-related morbidity events, defined as claims for emergency visits, inpatient hospitalizations, and ambulance transportation with substance use disorder or overdose diagnoses. Relative to initial treatment, risk was greater within individual during subsequent periods of >60 to 120 (adjusted odds ratio [OR], 1.29; 95% CI, 1.12 to 1.49) and >120 (OR, 1.48; 95% CI, 1.24-1.76) daily morphine milligram equivalents. Risk was also greater during days 1 to 30 after discontinuations than during initial treatment (OR, 1.19; 95% CI, 1.05-1.35). However, it was no greater than during the 30 days before discontinuations, indicating that the risk may not be wholly attributable to discontinuation itself. Results were supported by a negative control pharmacotherapy analysis and additional sensitivity analyses. They suggest that LtOT recipients may experience increased substance-related morbidity risk during treatment subsequent to initial opioid prescription, particularly in periods involving higher doses.Item Escalating costs of self-injury mortality in the 21st century United States: an interstate observational study(BMC, 2023-02-08) Rockett, Ian R. H.; Ali, Bina; Caine, Eric D.; Shepard, Donald S.; Banerjee, Aniruddha; Nolte, Kurt B.; Connery, Hilary S.; Larkin, G. Luke; Stack, Steven; White, Franklin M. M.; Jia, Haomiao; Cossman, Jeralynn S.; Feinberg, Judith; Stover, Amanda N.; Miller, Ted R.; Geography, School of Liberal ArtsBackground: Estimating the economic costs of self-injury mortality (SIM) can inform health planning and clinical and public health interventions, serve as a basis for their evaluation, and provide the foundation for broadly disseminating evidence-based policies and practices. SIM is operationalized as a composite of all registered suicides at any age, and 80% of drug overdose (intoxication) deaths medicolegally classified as 'accidents,' and 90% of corresponding undetermined (intent) deaths in the age group 15 years and older. It is the long-term practice of the United States (US) Centers for Disease Control and Prevention (CDC) to subsume poisoning (drug and nondrug) deaths under the injury rubric. This study aimed to estimate magnitude and change in SIM and suicide costs in 2019 dollars for the United States (US), including the 50 states and the District of Columbia. Methods: Cost estimates were generated from underlying cause-of-death data for 1999/2000 and 2018/2019 from the US Centers for Disease Control and Prevention's (CDC's) Wide-ranging ONline Data for Epidemiologic Research (WONDER). Estimation utilized the updated version of Medical and Work Loss Cost Estimation Methods for CDC's Web-based Injury Statistics Query and Reporting System (WISQARS). Exposures were medical expenditures, lost work productivity, and future quality of life loss. Main outcome measures were disaggregated, annual-averaged total and per capita costs of SIM and suicide for the nation and states in 1999/2000 and 2018/2019. Results: 40,834 annual-averaged self-injury deaths in 1999/2000 and 101,325 in 2018/2019 were identified. Estimated national costs of SIM rose by 143% from $0.46 trillion to $1.12 trillion. Ratios of quality of life and work losses to medical spending in 2019 US dollars in 2018/2019 were 1,476 and 526, respectively, versus 1,419 and 526 in 1999/2000. Total national suicide costs increased 58%-from $318.6 billion to $502.7 billion. National per capita costs of SIM doubled from $1,638 to $3,413 over the observation period; costs of the suicide component rose from $1,137 to $1,534. States in the top quintile for per capita SIM, those whose cost increases exceeded 152%, concentrated in the Great Lakes, Southeast, Mideast and New England. States in the bottom quintile, those with per capita cost increases below 70%, were located in the Far West, Southwest, Plains, and Rocky Mountain regions. West Virginia exhibited the largest increase at 263% and Nevada the smallest at 22%. Percentage per capita cost increases for suicide were smaller than for SIM. Only the Far West, Southwest and Mideast were not represented in the top quintile, which comprised states with increases of 50% or greater. The bottom quintile comprised states with per capita suicide cost increases below 24%. Regions represented were the Far West, Southeast, Mideast and New England. North Dakota and Nevada occupied the extremes on the cost change continuum at 75% and - 1%, respectively. Conclusion: The scale and surge in the economic costs of SIM to society are large. Federal and state prevention and intervention programs should be financed with a clear understanding of the total costs-fiscal, social, and personal-incurred by deaths due to self-injurious behaviors.Item Expert Panel Consensus on State-Level Policies to Improve Engagement and Retention in Treatment for Opioid Use Disord(American Medical Association, 2022-09-02) Smart, Rosanna; Grant, Sean; Gordon, Adam J.; Pacula, Rosalie Liccardo; Stein, Bradley D.; Social and Behavioral Sciences, School of Public HealthImportance: In the US, recent legislation and regulations have been considered, proposed, and implemented to improve the quality of treatment for opioid use disorder (OUD). However, insufficient empirical evidence exists to identify which policies are feasible to implement and successfully improve patient and population-level outcomes. Objective: To examine expert consensus on the effectiveness and the ability to implement state-level OUD treatment policies. Evidence review: This qualitative study used the ExpertLens online platform to conduct a 3-round modified Delphi process to convene 66 stakeholders (health care clinicians, social service practitioners, addiction researchers, health policy decision-makers, policy advocates, and persons with lived experience). Stakeholders participated in 1 of 2 expert panels on 14 hypothetical state-level policies targeting treatment engagement and linkage, evidence-based and integrated care, treatment flexibility, and monitoring or support services. Participants rated policies in round 1, discussed results in round 2, and provided final ratings in round 3. Participants used 4 criteria associated with either the effectiveness or implementability to rate and discuss each policy. The effectiveness panel (n = 29) considered policy effects on treatment engagement, treatment retention, OUD remission, and opioid overdose mortality. The implementation panel (n = 34) considered the acceptability, feasibility, affordability, and equitability of each policy. We measured consensus using the interpercentile range adjusted for symmetry analysis technique from the RAND/UCLA appropriateness method. Findings: Both panels reached consensus on all items. Experts viewed 2 policies (facilitated access to medications for OUD and automatic Medicaid enrollment for citizens returning from correctional settings) as highly implementable and highly effective in improving patient and population-level outcomes. Participants rated hub-and-spoke-type policies and provision of financial incentives to emergency departments for treatment linkage as effective; however, they also rated these policies as facing implementation barriers associated with feasibility and affordability. Coercive policies and policies levying additional requirements on individuals with OUD receiving treatment (eg, drug toxicology testing, counseling requirements) were viewed as low-value policies (ie, decreasing treatment engagement and retention, increasing overdose mortality, and increasing health inequities). Conclusions and relevance: The findings of this study may provide urgently needed consensus on policies for states to consider either adopting or deimplementing in their efforts to address the opioid overdose crisis.Item Perception of Resource Allocations to Address the Opioid Epidemic(Wolters Kluwer, 2022) Strickland, Justin C.; Victor, Grant; Ray, Bradley; School of Public and Environmental AffairsObjectives: Despite billions of dollars spent on opioid policy initiatives, public knowledge of evidence-based policies to reduce opioid-related morbidity remain low. Consequences of this knowledge gap for support of initiatives remains understudied. Our objective was to evaluate how participants with and without lived experience allocate funding for initiatives to address the opioid epidemic. A secondary objective was to collect proof-of-concept data of an informational intervention designed to improve support for evidence-based policies. Methods: Participants (N = 284; 57.2% female) without lifetime nonmedical opioid use (n = 98) and those with lifetime use (past year [n = 81] or nonpast year [n = 105]) of nonmedical opioids were recruited. All participants reported how they would allocate funds to demand reduction, supply reduction, harm reduction, and treatment policies. Half of all participants were then randomized to a brief informational intervention designed to emphasize evidence-based harm reduction and treatment programs. Results: Funding allocations were highest for policies related to community services and treatment and lowest for those related to harm reduction. Participants with lived experience allocated less to supply reduction policies. Participants (12%) who reallocated funds after information exposure increased funding to supervised consumption sites, dz = 0.77, naloxone distribution, dz = 0.85, syringe exchange programs, dz = 0.63, and medications for opioid use disorder access, dz = 0.70. Conclusions: This study illustrates how people with and without lived experience prioritize various policies to address the opioid epidemic and emphasize comparably low support for harm reduction policies. Proof-of-concept data suggest that brief informational interventions may increase funding support for harm reduction strategies, at least in a subset of people.Item The Pharmacology and Toxicology of Third-Generation Anticonvulsant Drugs(Springer Nature, 2017-12) LaPenna, Paul; Tormoehlen, Laura M.; Neurology, School of MedicineEpilepsy is a neurologic disorder affecting approximately 50 million people worldwide, or about 0.7% of the population [1]. Thus, the use of anticonvulsant drugs in the treatment of epilepsy is common and widespread. There are three generations of anticonvulsant drugs, categorized by the year in which they were developed and released. The aim of this review is to discuss the pharmacokinetics, drug-drug interactions, and adverse events of the third generation of anticonvulsant drugs. Where available, overdose data will be included. The pharmacokinetic properties of third-generation anticonvulsant drugs include relatively fewer drug-drug interactions, as well as several unique and life-threatening adverse events. Overdose data are limited, so thorough review of adverse events and knowledge of drug mechanism will guide expectant management of future overdose cases. Reporting of these cases as they occur will be necessary to further clarify toxicity of these drugs.Item Validating Imputation Procedures to Calculate Corrected Opioid-Involved Overdose Deaths, Marion County, Indiana, 2011-2016(Sage, 2020-01) Gupta, Sumedha; Cohen, Alex; Lowder, Evan M.; Ray, Bradley R.; Economics, School of Liberal ArtsObjectives: Understanding the scope of the current opioid epidemic requires accurate counts of the number of opioid-involved drug overdose deaths. Given known errors and limitations in the reporting of these deaths, several studies have used statistical methods to develop estimates of the true number of opioid-involved overdose deaths. This study validates these procedures using a detailed county-level database of linked toxicology and vital records data. Methods: We extracted and linked toxicology and vital records data from Marion County, Indiana (Indianapolis), during a 6-year period (2011-2016). Using toxicology data as a criterion measure, we tested the validity of multiple imputation procedures, including the Ruhm regression-based imputation approach for correcting the number of opioid-involved overdose deaths. Results: Estimates deviated from true opioid-involved overdose deaths by 3% and increased in accuracy during the study period (2011-2016). For example, in 2016, 231 opioid-involved overdose deaths were noted in the toxicology data, whereas the corresponding imputed estimate was 233 opioid-involved overdose deaths. A simple imputation approach, based on the share of opioid-involved overdose deaths among all drug overdose deaths for which the death certificate specified ≥1 drug, deviated from true opioid-involved overdose deaths by ±5%. Conclusions: Commonly used imputation procedures produced estimates of the number of opioid-involved overdose deaths that are similar to the true number of opioid-involved overdose deaths obtained from toxicology data. Although future studies should examine whether these results extend beyond the geographic area covered in our data set, our findings support the continued use of these imputation procedures to quantify the extent of the opioid epidemic.Item Visual Analytics for Data-Driven Understanding of the Substance Use Disorder Epidemic(Sage, 2024) Qaurooni, Danial; Herr, Bruce W., II; Zappone, Sarah Renee; Wojciechowska, Klaudia; Börner, Katy; Schleyer, Titus; Medicine, School of MedicineThe substance use disorder epidemic has emerged as a serious public health crisis, presenting complex challenges. Visual analytics offers a unique approach to address this complexity and facilitate effective interventions. This paper details the development of an innovative visual analytics dashboard, aimed at enhancing our understanding of the substance use disorder epidemic. By employing record linkage techniques, we integrate diverse data sources to provide a comprehensive view of the epidemic. Adherence to responsive, open, and user-centered design principles ensures the dashboard's usefulness and usability. Our approach to data and design encourages collaboration among various stakeholders, including researchers, politicians, and healthcare practitioners. Through illustrative outputs, we demonstrate how the dashboard can deepen our understanding of the epidemic, support intervention strategies, and evaluate the effectiveness of implemented measures. The paper concludes with a discussion of the dashboard's use cases and limitations.