Doctor of Philosophy, Case Western Reserve University, 2021, Anthropology

In an effort to combat the staggeringly high rates of opioid overdose deaths in the US, Overdose Education and Naloxone Distribution (OEND) clinics were established. This study was a collaborative partnership with a local urban hospital committed to harm reduction through their community-based OEND clinic. This study's purpose was twofold. First, to understand who utilized OEND clinics and the factors affecting their HSB (i.e. number of Naloxone kits). Second, to understand how OEND clients framed their understanding of their SUD and if their model of addiction affected HSB. The study was comprised of three distinct phases. Phase 1 Quantitative assessment examined the demographic characteristics (i.e., gender, race, education, SES, occupation), mental health concerns (i.e., anxiety, depression & general distress), breadth and satisfaction of social support, and addiction beliefs in 235 clients from a local OEND clinic in Cleveland, Ohio. Since all participants in this study were already a part the OEND clinic, the number of naloxone kits will serve as a proxy for HSB. Phase 2 Qualitative Assessment explored how 61 of the enrolled clients framed their understanding of their substance use disorder (SUD). Qualitative interviews were coded for themes related to SUD beliefs, the type of stigma experienced by clients as a function of their drug use, and their motivation behind the decisions to seek out Naloxone. Phase 3 involved informal clinic observations to understand clients' experiences and interactions with OEND clinic staff. Gaining a better understanding of patients' health-seeking behaviors (HSB) at OEND clinics is a critical first step along the road to combatting the opioid epidemic. Phase 1 data revealed that clients who chose to engage in the HSB of OEND clinic were primarily unemployed, Caucasian males who were approximately 38 years of age. They were highly anxious, depressed, and in need of more social support to assist in their recovery. The majorit (open full item for complete abstract)

Committee: Lee Hoffer (Committee Chair); Janet McGrath (Committee Member); Jill Korbin (Committee Member); Brian Gran (Committee Member) Subjects: Behavioral Sciences; Cultural Anthropology; Health; Mental Health; Public Health; Social Research

PHD, Kent State University, 2017, College of Public Health

This study evaluates the acceptability of pharmacy based opioid misuse and abuse interventions by surveying practicing pharmacists and patients in treatment for substance use disorders. The survey instrument examines five specific pharmacy-based interventions using a Likert scale to measure acceptability: (1) Pharmacists counseling patients on the risks associated with opioid misuse and abuse, (2) pharmacists referring patients to drug treatment programs within the community, (3) pharmacists utilizing Prescription Drug Monitoring Programs (PDMPs) to validate prescriptions, (4) pharmacists providing emergency opioid overdose treatments such as naloxone with opioid prescriptions, and (5) pharmacists providing naloxone without a prescription. The goal of this study is to answer three research questions: which interventions are most acceptable to pharmacists, which interventions are most acceptable to patients, and which interventions produce statistically significant agreement on acceptability when both pharmacist and patient attitudes are compared. These data are used to identify a subset of interventions with high acceptability within and across the two groups. These findings are, in turn, used as an indication of professional and patient receptivity to specific interventions. The interventions with the greatest acceptability within each group and the strongest agreement across groups are identified, and changes to State regulations, organizational policy, and professional training that foster these interventions, as supported by the literature, are proposed.

Committee: Sonia Alemagno PhD (Committee Chair); VanGeest Jonathan PhD (Committee Member); Phillips Lynette PhD (Committee Member); Deric Kenne PhD (Committee Member); Mark James PhD (Other) Subjects: Pharmacy Sciences; Public Health Education; Public Policy

PHD, Kent State University, 2024, College of Arts and Sciences / School of Biomedical Sciences

Opioid addiction and opioid use disorder (OUD) is one of the major problems that we are facing not only in the US but all around the world. An estimated 3 million US citizens and 16 million people worldwide suffer from OUD by 2022. This number is expected to keep rising in the coming years. One of the leading causes of death related to OUD is opioid-induced respiratory depression (OIRD), in which overdose is accompanied by into respiratory arrest; the individual can die if not treated promptly. Currently, the only approved treatment modality for OIRD is a drug known as naloxone which is administered by emergency personnel to an individual who has overdosed on opioids and is suffering from OIRD. Naloxone as a drug also has its own issues like a short half-life; this precipitates withdrawal and blocks the analgesic effects of opioids. One of the major problems associated with naloxone is the potential need for repeated administration of higher doses to counter the effects of fentanyl and its analogs at the epicenter of this epidemic. This has made it necessary for development of new more efficient drugs with lesser side effects to counter this epidemic. Neuronal signaling from the superior cervical ganglion (SCG) is shown to modulate respiratory dynamics at least in part. The aim of this study was to deduce the effect of a novel thiol ester D-Cysteine ethyl ester (D-CYSee) on fentanyl-mediated effects on intrinsic Ca2+ activity in the SCG and to determine how it compares to naloxone. We used real-time Ca2+ imaging to deduce changes in intrinsic Ca2+ activity in response to voltage-gated Na+ and Ca2+ channel blockersand naloxone in presence and absence of fentanyl, and D-CYSee in presence and absence of fentanyl in cells isolated from the SCG. Key outcomes from our studies show that 1) cells receiving drug-free control treatment showed consistent activity and extracellular Ca2+ was key for the activity; 2) the activity was driven primarily by L-type calcium channels a (open full item for complete abstract)

Committee: Derek Damron Dr. (Advisor); Colleen Novak Dr. (Advisor); Lee Gilman Dr. (Committee Member); Gary Koski Dr. (Committee Member); Jennifer McDonough Dr. (Committee Member); Stephen Lewis Dr. (Committee Member) Subjects: Biology; Biomedical Research; Cellular Biology; Neurosciences

PhD, University of Cincinnati, 2022, Arts and Sciences: Chemistry

Reactive oxygen species are a group of highly reactive oxygen-containing entities that are important at a cellular level for multiple biological processes. Low concentrations of ROS can be beneficial as powerful signaling molecules in those biological processes, although excessive concentrations can promote high levels of DNA damage and a variety of diseases such as skin cancer. A newly identified intracellular ROS production source in skin cells is NADPH oxidases. Out of the NOX enzyme family, the NOX1 holoenzyme is most abundantly expressed in the human keratinocyte cells. UV radiation can trigger the activation of NOX1 isoforms which stimulate the assembling of member CYBA and the cytoplasmic protein NOXO1. Inhibition of these enzymes represents a catalytic approach toward reducing ROS for the prevention of ROS inducible diseases. Key disease states include melanoma induced by UV exposure. The first half of the dissertation focuses on investigating new small molecule inhibitors of a key NOX1 holoenzyme to address these challenges. We designed a series of molecules by optimizing the structure of diapocynin and evaluated by in-silico docking methods to determine the binding affinity with NOXO1 cytoplasmic protein (1WLP crystal structure). And have synthesized the series of target molecules for the structure-activity relationship studies. In the first section of the project, we discovered that inhibitor NOX_inh_5 was not cytotoxic, but instead improved the viability of human primary cells from UV exposure, decreased the cellular stress in human skin through the p53 pathway, and reduced the UV-induced DNA damage as monitored by quantification of cyclobutane dimer formation after UV exposure. Then, we characterized the inhibition potential of NOX_inh_5 by using an Isothermal calorimetric (ITC) binding assay and heteronuclear single quantum coherence (HSQC) technique and revealed that the candidate molecule can prevent the complex formation of NOXO1 and CYBA me (open full item for complete abstract)

Committee: Edward Merino Ph.D. (Committee Member); Peng Zhang Ph.D. (Committee Member); In-Kwon Kim Ph.D. (Committee Member) Subjects: Pharmaceuticals

PhD, University of Cincinnati, 2020, Pharmacy: Pharmaceutical Sciences/Biopharmaceutics

Background: Prescription drugs in general, and opioids in particular, are now the second-most abused substance, after marijuana in young adults. More than 42,000 Americans died from opioid overdose in 2016, which is more than a 100% increase from 2010. Naloxone is a controlled substance that reverses the respiratory and central nervous system depression which is caused by opioid overdose. In the last few years many states have implemented a law called physician-approved protocol in order to increase the access to this life saving drug. Goal of this study was to evaluate the impact of this law on the naloxone dispensing rate. Objectives: To determine the association between a pharmacist naloxone dispensing law and naloxone dispensing rates in Ohio. To determine the impact of the physician-approved protocol on naloxone dispensing rates nationally. Methods For the first objective we used Ohio Medicaid and Kroger pharmacy claims for the 88 counties in Ohio. Area Health Resource File was used to incorporate the county level variables. Any patient 18 years or older with at least 1 naloxone order dispensed through Ohio Medicaid or filled by a Kroger pharmacy in Ohio during the study period of July 16, 2014, to January 15, 2017, was included in the study. A segmented regression analysis of an interrupted time series was performed for 30 consecutive months to evaluate the change in the naloxone dispensing rate before and after the implementation of the state law. For the second objective, we used national Kroger data which included data for 31 states and Area Heath Resource File (AHRF) data set for the state level variables. The study sample included all patients who received at least one naloxone prescription that was filled in any Kroger pharmacy during the study period from July 16, 2014 to January 16, 2017. A multiple regression analysis was performed for 30 consecutive months to evaluate the change in naloxone prescription dispensing rate. Results In th (open full item for complete abstract)

Committee: Pamela Heaton Ph.D. (Committee Chair); Jill Boone Pharm.D. (Committee Member); Stacey Frede Pharm.D. (Committee Member); Ana Hincapie Ph.D. (Committee Member); Roman Jandarov Ph.D. (Committee Member) Subjects: Pharmaceuticals

DNP, Otterbein University, 2017, Nursing

The opioid overdose epidemic continues to escalate in the United States. Some of the morbidity and mortality associated with opioid overdose can be prevented with the timely administration of naloxone, an opioid reversal agent. The literature emphasized that the emergency department (ED) venue and registered nurses are well positioned to screen and identify high risk individuals whether they present as a result of an overdose or for other medical reasons. The literature also pointed to the importance of providing naloxone to high risk individuals and those who would be most likely to be at the scene of an overdose. This is critical because most overdoses occur at home. Additionally, negative attitudes and stigmatization towards individuals with substance use disorders (SUD) can result in provision of suboptimal patient care for this population. The literature demonstrated that education can improve knowledge gaps and negative attitudes towards patients with SUD. The purpose of this evidence-based practice improvement project (EBPI) was to address the knowledge gaps and attitudes of Emergency Department Registered Nurses (EDRNs) about the scope of the opioid overdose epidemic, SUDs as a disease, pathways from prescription opioids to heroin, treatment, recovery, harm reduction education, and nasal naloxone spray. The goal of the EBPI was to use evidence to increase the EDRNs' knowledge and improve attitudes to facilitate delivery of evidence-based care. The clinical question guiding the EBPI was “In EDRNs caring for patients at high risk for opioid overdose, how does providing a standardized education intervention about harm reduction education and naloxone nasal spray (HRENNS), compared to not providing standardized education, affect the EDRNs' knowledge and attitudes about providing HRENNS to patients at high risk for opioid overdose, measured immediately and 30 days following completion of the education intervention.” The project framework included Plan, D (open full item for complete abstract)

Committee: Eva Fried DNP, WHNP (Committee Chair); John Chovan PhD, DNP, RN, CNP, CNS (Committee Member); Jennifer Biddinger Mpsy (Committee Member) Subjects: Health Care; Mental Health; Nursing

Doctor of Philosophy, The Ohio State University, 1985, Graduate School

Committee: Not Provided (Other) Subjects: Language

Doctor of Philosophy, The Ohio State University, 1985, Graduate School

Committee: Not Provided (Other) Subjects: Biology

Doctor of Philosophy, The Ohio State University, 1981, Graduate School

Committee: Not Provided (Other) Subjects: Psychology

Doctor of Philosophy, The Ohio State University, 1979, Graduate School

Committee: Not Provided (Other) Subjects: Health Sciences

Doctor of Philosophy, The Ohio State University, 1975, Graduate School

Committee: Not Provided (Other) Subjects: Chemistry

Ph.D., Antioch University, 2016, Leadership and Change

Opioid dependence has reached epidemic levels in the United States and around the world. With the increased prescribing of opioid pharmaceuticals and the influx of inexpensive heroin, the health care cost to society has topped $72.5 billion annually (Murphy et al., 2016). Opioid overdose deaths have now surpassed motor vehicle deaths and have tripled since 1990. In some age groups opioid overdose is the leading cause of death. This study seeks to analyze the only field that directly treats this primary brain disease: medication assisted treatment for opioid dependence. The three primary participants in this partnership include: (a) doctors and allied medical providers; (b) substance abuse counselors known in Washington State as Chemical Dependency Professionals (CDPs); and (c) clients affected by opioid dependence. Together they combine medical approaches and psychosocial counseling with clients to attain the goal of recovery. Attitudes and beliefs of these three groups of individuals vary, as do their views toward the medications currently being utilized in the treatment field. This study measures these differences and discusses the implications for clients, medical providers, and CDPs. It was hypothesized that differences in opinions across the three groups about medication assisted treatment, length of time clients should be on medications, and recovery limit positive outcomes. Data were collected via survey from more than 250 clients being treated for opioid dependency and from over 200 professionals (medical and counseling). Descriptive and comparative ANOVA and t-test statistics were used in the analysis. Results indicate that there remain large differences in beliefs and attitudes among the medical providers, CDPs, and clients on key issues related to medication assisted treatment. The gap appears to be especially evident when comparing the two professional groups who treat clients with opioid use disorder. CDPs and medical providers are working from a dif (open full item for complete abstract)

Committee: Carol Baron PhD (Committee Chair); Jon Wergin PhD (Committee Member); Stacy Rasmus PhD (Committee Member); Adam Kartman MD (Committee Member); Monica Skewes PhD (Other) Subjects: Counseling Psychology; Medicine; Pharmaceuticals

PhD, University of Cincinnati, 2015, Nursing: Nursing - Doctoral Program

This dissertation study aimed to evaluate the feasibility of an innovative group-based opioid overdose educational intervention in individuals at high-risk for overdose. Opioid overdose is the leading cause of injury death in the United States and overdose fatalities have more than tripled in the past 25 years. Fatal opioid overdoses have been declared an epidemic by the Centers for Disease Control and Prevention and can be reversed by the timely administration of naloxone, brand name Narcan®. There are approximately 188 opioid overdose prevention programs (OOPPs) distributing naloxone to individuals at high-risk for witnessing an overdose and there is vital need to expand the dissemination of interventions that reduce the risk of overdose and expand access to naloxone. In 2013, the Substance Abuse and Mental Health Services Administration (SAMHSA) released the Opioid Overdose Prevention Toolkit to assist OOPPs in the development and implementation of opioid overdose prevention efforts. However, in its current format the toolkit is not amenable for use in the group setting. Therefore, the overall purpose of this feasibility study was to develop a group-based OOPP educational intervention and determine the implementation fidelity and intervention effect size. Specifically this study aimed to: 1). Modify the SAMHSA Opioid Overdose Prevention Toolkit for use in the group setting; 2). Determine whether clinicians, who have received training, can deliver the intervention with implementation fidelity in the group setting; 3). Determine participant responsiveness to the intervention; 4). Determine the intervention effect size. A total of 49 subjects, receiving inpatient treatment for opioid dependence, participated in the educational intervention. Participants completed a pre-test and a post-test to determine their knowledge about preventing overdoses, risk factors for overdose, and responding to overdoses, including the administration of naloxone. The end product of this (open full item for complete abstract)

Committee: Donna Martsolf Ph.D. R.N. (Committee Chair); Yvette Pryse Ph.D. (Committee Member); Erin Winstanley Ph.D. (Committee Member) Subjects: Nursing

MS, University of Cincinnati, 2012, Medicine: Clinical and Translational Research

Background: Medication errors are a common cause of injuries sustained in hospitals and up to 6% are related to opioids. A challenging task for clinicians is to find the perfect balance between providing effective analgesia and preventing adverse events Objective: Evaluate the incidence and risk factors associated with opioid overdose in a non-surgical inpatient population. Methods: A case-control study based on information from the electronic health record following discharge from a large community hospital in Cincinnati, OH between June and December 2008. Participants were adults hospitalized on medical wards and receiving opioid therapy. Cases met clinical criteria for opioid overdose and were treated with Naloxone, while. controls were randomly selected from the same time interval. We excluded patients admitted for opioid overdose, those on patient controlled analgesia, or those in a perioperative setting including same-day outpatient procedures. Main Measures: Opioid overdose events, patient demographics, laboratory values, comorbidities, type and number of opioids used, dose in morphine equivalents and other psychotropic medications used. Results: Of a total of 19,111 patient discharges, 40 (0.21%) met the case inclusion criteria for opioid overdose. Patients with overdoses had a lower weight and were receiving higher opioid doses both prior and during the hospitalization. Hydromorphone was the opioid most frequently associated with overdose events while Hydrocodone was the least. Multivariate logistic regression analyses showed older age (OR 1.06 [95% CI 1.01 to 1.11], p= 0.012), serum creatinine (OR 1.36 [95% CI 1.07 to 1.73], p=0.011) and 24-hour total morphine equivalents received (OR 1.01 [1.00 to 1.02], p=0.002) to be most highly associated with overdose. Hydrocodone use (OR 0.12 [95% CI 0.02 to 0.69], p=0.018) was associated with a decreased risk of overdose. Conclusions: Opioid overdose events were more frequent among older patients with increased cr (open full item for complete abstract)

Committee: Erin Nicole Haynes DrPH (Committee Chair); Mark Eckman MD (Committee Member); Mark Wess MD (Committee Member) Subjects: Surgery

Doctor of Philosophy, The Ohio State University, 2006, Oral Biology

Activation of neuroendocrine responses by restraint stress (RST) suppresses natural killer cell (NK) activity during an experimental influenza A/PR8 viral infection. RST-induced activation of the HPA axis upregulates glucocorticoids (GC) and endogenous opioids which may be responsible for the observed suppression of NK activity. GC receptor antagonism modulates trafficking and splenic cellularity. However, the specific effects on NK activity remain unclear. Opioid receptor antagonism with naltrexone (NTX) abrogates RST-induced suppression of splenic NK cytotoxicity suggesting endogenous opioids modulate NK cytotoxicity. However, the specific subtype of opioid receptors involved remains unclear. These studies examined the effects of GC and specific opioid receptor subtype antagonism on splenic NK cellularity and cytotoxicity. Additionally, these studies examined whether the opioid signaling mechanism involved a direct effect on NK cells or a possible modulation in NK-stimulatory cytokine mRNA expression. C57BL/6 mice were treated daily with the GC receptor antagonist RU486, the opioid receptor antagonist NTX, or i-, a-, or e-opioid receptor specific antagonists. Mice were infected intra-nasally with A/PR8 virus and underwent daily RST. Splenocytes were obtained three days post infection. For in vitro studies, splenocytes were incubated with NTX or morphine (MOR) and tested for cytolytic activity at 24 and 48 hours. NK cytotoxicity was assessed using a standard chromium release assay. FACS analysis was used to detect the number of CD3-DX5+ NK cells. Cytokine mRNA expression was assessed using realtime PCR. RST-induced suppression of NK activity was a result of decreases in number of splenic NK cells and cytotoxicity. GC Receptor antagonism restored cellularity and i-opioid receptor antagonism restored NK cytolytic activity. Splenic NK cells incubated with morphine or NTX for up to 48 hours showed no change in NK cytotoxicity. Preliminary data suggested that antagonism (open full item for complete abstract)

Committee: John Sheridan (Advisor) Subjects: