This study examines the effects of gender and social bonds on the experience of prescription painkiller misuse for men and women. The theoretical framework for the project is Travis Hirschi's social control theory (1969), and the social bond elements of attachment, commitment, involvement, and belief, which emphasizes the importance of these bonds in creating a "stake in conformity" for the individual, leading to acceptance of social norms and desistence from deviance. This theory, however, is relatively silent with regard to gender differences and was developed to examine delinquency in an all male sample of adolescents. The elements of this theory were used to further test the effects of these social bonds and add to the literature gap on the gendered experience of the misuse of prescription painkillers. Data for this project comes from the 2011 National Survey on Drug Use and Health, an annual nationally representative, cross-sectional survey. Multivariate logistic regression analyses reveal that, being white, not being married, having less than a high school diploma, a having a job are all significant predictors of increased prescription painkiller misuse. Characteristics associated with a significant decrease in the odds of misusing prescription painkillers are being older, having a college degree, and placing importance on religious/spiritual beliefs. Multivariate logistic regression also reveals that female respondents are less likely to misuse prescription painkillers than are their male counterparts. Interaction effects are operationalized to measure the relationship between gender and the social bond elements of interest. Most of the interaction effects are not statistically significant, but some of the main effects remain significant, which indicates that the main effect has little impact on prescription painkiller misuse for women, but remains significant for men (marriage, education, work status). Significant interaction effects are found for gender (female) x income and gender (female) x religiosity, which indicates that for both men and women, increased income and higher levels of religiosity are significantly associated with decreased odds of prescription painkiller misuse, that the effect is stronger for women and that this difference between men and women is significant. These results provide further insight into the experiences of prescription painkiller misuse for men and women.

Background Gabapentinoids (gabapentin and pregabalin), a class of FDA-approved antiepileptic medications with expanded indications for certain neuropathic pain conditions, have been prescribed off-label for almost all types of pain in the US opioid epidemic. Methods We used IBM® MarketScan® Research Databases (2015-2018) and collected primary data. In Aim 1, we described the geographic variation in gabapentinoids and opioids for pain by US state and metropolitan statistical area (MSA). In Aim 2, we implemented a controlled multiple baseline interrupted time series analysis and assessed the impact of including gabapentin in states’ prescription drug monitoring programs (PDMP) and listing gabapentin as a Schedule V controlled substance. In Aim 3, we developed an algorithm to identify potential gabapentin misuse and/or abuse in administrative claims data. Results The pattern of the geographic variation in gabapentinoids was similar to that of opioids across states and MSAs. Including gabapentin in PDMPs and Schedule V controlled ABSTRACT viii substance classification were effective in curbing the growth of gabapentin use and reducing opioid-related adverse events. Our algorithm identified approximately one in six patients with gabapentin use as having potentially misused and/or abused gabapentin. Multiple comorbidities and drug use were associated with gabapentin misuse and/or abuse. Conclusions Gabapentinoids may have been widely used as alternative or adjuvant analgesics to opioids for pain across the US. Policy makers should consider including gabapentin in proactive PDMPs and scheduling of gabapentin. Monitoring requirements and individualized safety measures should be put in place for patients who potentially misuse and/or abuse gabapentin.

Indiana University-Purdue University Indianapolis (IUPUI) / Pharmacogenetic testing has the potential to improve pain management through addressing wide interindividual variations in responses to pharmacogenetically actionable opioids, ultimately decreasing costly adverse drug effects and improving responses to these medications. A recent review of pharmacogenomics in the nursing literature highlighted the need for nurses to more fully embrace the burgeoning field of pharmacogenomics in nursing research, clinical practice, and education. Despite the promise of pharmacogenetic testing, significant challenges exist for evaluating outcomes related to its implementation, including oversimplification of medication exposure, the complexity of patients' clinical profiles, and the characteristics of healthcare contexts in which medications are prescribed. A better understanding of these challenges could enhance the assessment and documentation of the benefits of pharmacogenetic testing in guiding opioid therapies. This dissertation is intended to address the challenges of evaluating outcomes of pharmacogenetic testing implementation and the need for nurses to lead pharmacogenomic-related research. The dissertation purpose was to advance the sciences of nursing, pain management, and pharmacogenomics through the development of a typology of common patterns of medication exposure to known pharmacogenetically actionable opioids (codeine & tramadol). A qualitative, person-oriented approach was used to retrospectively analyze six months of electronic health record and pharmacogenotype data in 30 underserved adult patients. An overarching typology with eight groups of patients that had one of five opioid prescription patterns (singular, episodic, switching, sustained, or multiplex) and one of three types of medical emphasis of care (pain, comorbidities, or both) were identified. This typology consisted of a description of multiple common patterns that compare and contrast salient factors of exposure and the emphasis of why individuals were seeking care. Furthermore, in an aggregate descriptive analysis evaluating key clinical profile factors, these patients had complex medical histories, extensive healthcare utilization, and experienced significant polypharmacy. These findings can aid in addressing challenges related to the implementation of pharmacogenetic testing in clinical practice and point to ways in which nurses can take the lead in pharmacogenomics research. Findings also provide a foundation for future studies aimed at developing medication exposure measures to capture its dynamic nature and identifying and tailoring interventions in this population.

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This review will focus on a systems medicine approach to neonatal abstinence syndrome (NAS). Systems medicine utilizes information gained from the application of “omics” technology and bioinformatics (1). The omic approaches we will emphasize include genomics, epigenomics, proteomics, and metabolomics. The goals of systems medicine are to provide clinically relevant and objective insights into disease diagnosis, prognosis, and stratification as well as pharmacological strategies and evidence-based individualized clinical guidance. Despite the increasing incidence of NAS and its societal and economic costs, there has been only a very modest emphasis on utilizing a systems medicine approach, and this has been primarily in the areas of genomics and epigenomics. As detailed below, proteomics and metabolomics hold great promise in advancing our knowledge of NAS and its treatment. Metabolomics, in particular, can provide a quantitative assessment of the exposome, which is a comprehensive picture of both internal and external environmental factors affecting health.

Indiana University-Purdue University Indianapolis (IUPUI) / Naltrexone (NTX) is clinically efficacious at attenuating alcohol intake in non-abstinent alcoholics and, to a lesser extent, craving, independent of intake. While generally regarded as a non-selective opioid antagonist, NTX has been shown to have concentration dependent selectivity with lower doses (< 1.0 mg/kg) selective for the mu receptor and doses exceeding 1.0 mg/kg capable of binding to delta and kappa receptors. Like the mu system, the delta receptor system has also been implicated in mediating the rewarding effects of EtOH. In contrast, the role of the kappa system is less clear though recent evidence suggests that kappa activation may mediate EtOH aversion. Thus, the present study sought to evaluate the effects of both mu-selective and non-selective doses of naltrexone, the selective delta antagonist naltrindole (NTI), and the selective kappa agonist U50,488H (U50) in a paradigm that procedurally separates the motivation to seek versus consume a reinforcer to assess whether these receptor-selective drugs differentially affects these behaviors in both selected (alcohol-preferring P rats) and non-selected (Long Evans) rats, and whether these effects are specific to EtOH. Rats were trained to complete a single response requirement that resulted in access to either 2% sucrose or 10% EtOH for a 20-min drinking session. In three separate experiments, rats were injected (using a balanced design) with either vehicle or 1 of 3 doses of drug: U50 (IP; 2.5, 5.0, or 10.0mg/kg), NTI (IP; 2.5, 5.0, or 10.0 mg/kg), low NTX (SC; 0.1, 0.3, or 1.0 mg/kg) or high NTX (SC; 1.0, 3.0, or 10.0 mg/kg) on both consummatory and appetitive treatment days. Following either a 20 (U50), 15 (NTI), or 30 minute (NTX) pretreatment, rats were placed into an operant chamber and intake (consummatory) or lever responses (appetitive) and response latencies were recorded. The results showed that overall: U50, NTI, and NTX attenuated intake and responding for sucrose and EtOH. Independent of reinforcer, LE rats were more sensitive to U50’s effects on intake while P rats were more sensitive to the effects on seeking. P rats reinforced with EtOH were more sensitive to NTI’s effects on intake and seeking than all other rat groups. P rats were more sensitive overall to lower doses of NTX than LE rats and lower doses of NTX were more selective in attenuating EtOH responding vs. sucrose. Higher doses of NTX suppressed intake and responding across both lines and reinforcers. These results demonstrate that craving and intake may be differentially regulated by the kappa, delta, and mu opioid receptor systems as a function of “family history” and suggest that different mechanisms of the same (opioid) system may differentially affect craving and intake.

<p>Miniaturization of technologies to milli-, micro- and nanoscale offers numerous advantages for diagnostic and therapeutic biomedical applications. In comparison to their macro-scale counterparts, these small-scale systems are more portable, less invasive and less costly. They can facilitate rapid, sensitive and high throughput detection of abnormalities, help track disease progression, reduce sample consumption and improve therapeutic efficacy of drug delivery while decreasing systemic toxicity. Thus, there is clearly a need for creating innovative milli-, micro- and nanoscale tools that can uncover new possibilities in detection and treatment of various types of diseases. The overall objective of this dissertation was to develop novel small-scale technologies that could help enhance diagnostic and/or therapeutic outcomes in patients with cancer, opioid addiction and inflammatory bowel disease. First, we developed an echogenically stable nanodroplet ultrasound contrast agent with potential applications in extravascular molecular imaging of tumors and targeted cancer therapies. Then, we created a polymer blend microsphere system that could be integrated in prescription opioid tablets to develop an abuse-deterrent formulation against smoking. Finally, we designed a release system for localized delivery of aminosalicylates from magnetically actuated millirobots in the colon to improve therapeutic outcomes in patients suffering from inflammatory bowel disease. Overall, the technologies we developed could serve as a basis for designing diagnostic and therapeutic tools that are superior to currently existing platforms.</p>