Doctor of Nursing Practice, Mount St. Joseph University , 2021, Department of Nursing

Pediatric delirium remains to be a significant cause of negative patient outcomes. Prevalence rates of pediatric delirium in pediatric intensive care units (PICU) have increased from 20% to at least 40% in the last couple of years. Despite these rates, very few PICUs screen for delirium. The global aim of this project included increasing knowledge and awareness of PD, thereby, decreasing PRN benzodiazepine boluses. The outcome goal of this project was the implementation and standardization of delirium screening tools into practice at the participating organization. A total of 29 staff nurses participated in an education pre and posttest. Posttest scores increased with 52% of participants achieving an 88% or higher on the quiz leading to a statistically significant increase in test scores from pre-test to post-test, Z=4.58, p <0.00001. Out of 40 patients, only 12 (30%) patients were actually screened demonstrating minimal scale compliance. There was no significant difference in mean number of boluses between patients who received care pre-intervention (M = 0.89 boluses/day) and patients who received care post-intervention (M =0.76 boluses/day), t(410) = 1.06, p = 0.145; however, data demonstrated an average drop of 0.13 boluses given in a 24 hour period and a 5% increase in patients that did not receive a PRN bolus the entire length of stay. The findings of this study serve as the first of many steps toward changing culture at the participating organization and in healthcare by promoting changes in care that minimize the morbidities associated with pediatric delirium, thereby, improving patient outcomes.

Committee: Kristin Clephane DNP, RN, CPN (Advisor) Subjects: Health Care; Medicine; Nursing; Pharmaceuticals

Psy. D., Antioch University, 2020, Antioch New England: Clinical Psychology

Numerous concerns have emerged regarding the dangers of extended benzodiazepine use and abuse, as well as continued prescribing by medical professionals despite related contraindications. Primary care physicians (PCPs) may find decisions around benzodiazepine prescription and related patient encounters to be especially challenging. Little is known on the efficacy of routine medical training and supervision/consultation models in preparing emerging PCPs for managing the dilemmas that may ensue with regards to prescribing benzodiazepines. The present study sought to begin addressing this gap by conducting an initial qualitative inquiry into the training and supervision experiences and needs of a group of current family medicine residents. A 30-minute semi-structured focus group interview (consisting of four participants) was conducted via video. Two main themes, Variability in Resources and Supports and Patient–Provider Interactions, were identified through thematic analysis. Participants highlighted concerns that inconsistencies in resources and supervisory approaches to benzodiazepines might adversely impact their therapeutic relationship with patients, and an initial hypothesis regarding this possible association was presented for further research. Participants identified increased empathy from supervisors around this concern as a primary area of need for future support. Limitations of the study, implications for practice, and future directions for research were discussed. The present study found that a better understanding of the early training and supervision experiences of emerging primary care providers around benzodiazepines will be critical in supporting the next generation of providers, improving patient care, and shaping future prescribing practices related to this difficult class of medications.

Committee: Roger Peterson PhD, ABPP (Committee Chair); F Alexander Blount EdD (Committee Member); Karen Meteyer PhD (Committee Member) Subjects: Clinical Psychology; Health Care; Medicine; Pharmaceuticals

Doctor of Philosophy, The Ohio State University, 2015, Dentistry

Psychosocial stress promotes brain-to-immune and immune-to-brain communication that can impact neurobiology and behavior. Exposure to stress may cause peripheral immune dysregulation and neuroinflammatory signaling by repeated activation of neuroendocrine and autonomic pathways; that may contribute to the development of mental health disturbances. In order to relieve anxiety and depression accompanying stress, physicians resort to anxiolytics and antidepressants. Lorazepam and clonazepam are anxiolytics that act by enhancing GABAergic activity in the brain. Moreover, imipramine, a tricyclic antidepressant, has been reported to influence immune function in depressed patients. The stress model of repeated social defeat (RSD), recapitulates many of the stress-driven alterations in both the periphery and central nervous system seen in humans experiencing chronic or repeated forms of stress. For example, RSD triggered egress of inflammatory myeloid progenitor cells that traffic to blood, spleen and brain. RSD promoted brain region-specific activation of microglia/macrophages that led to prolonged anxiety. In parallel, RSD promoted long-lasting social avoidant behavior. Thus, the overall aim of this dissertation was to determine if pharmacologic blockade of the GABAergic and monoaminergic circuits using lorazepam, clonazepam, and imipramine, respectively, would: 1) prevent stress-induced peripheral and central inflammatory responses, and 2) block anxiety and social avoidance behavior in mice subjected to RSD. Lorazepam or clonazepam prior to stressor exposure affected central and peripheral responses. Treatment with either drug was effective in attenuating mRNA expression of corticotropin-releasing hormone (CRH) in the hypothalamus and corticosterone in plasma in mice subjected to RSD. Both drugs blocked stress-induced elevated levels of IL-6 in plasma. Lorazepam and clonazepam had different effects on stress-induced enhancement of myelopoiesis and inhibited t (open full item for complete abstract)

Committee: John Sheridan (Advisor); Ning Quan (Committee Member); John Walters (Committee Member); Michael Bailey (Committee Member) Subjects: Immunology; Neurosciences

Doctor of Psychology (PsyD), Wright State University, 2014, School of Professional Psychology

This translational research piece involved collaborating with a local community mental health agency to examine knowledge, skills, attitudes, practices, and outcomes for panic disorder treatments. The project included designing and administering an online survey to client care personnel including psychologists, counselors, social workers, nurses, and psychiatrists. Additionally, a database review was utilized to obtain information about treatment modalities, duration, and outcomes. Survey results were analyzed using goodness of fit statistics to show differences between attitudes of participants by discipline regarding the safety and effectiveness of panic disorder treatments. The database analysis of pre and post GAF scores revealed comparable outcomes for therapy alone and therapy and medication treatment groups. Additionally, clients receiving therapy and medication for panic disorder were shown to have had significantly longer treatment duration on average than those in therapy only. These findings were discussed in terms of existing literature on panic disorder treatment and organizational change to make recommendations for the participating agency and others like it.

Committee: J. Scott Fraser Ph.D., ABPP (Committee Chair); Leon VandeCreek Ph.D., ABPP (Committee Member); Jeffery Allen Ph.D., ABPP (Committee Member) Subjects: Psychology; Psychotherapy; Public Health

PhD, University of Cincinnati, 2003, Arts and Sciences : Chemistry

Several novel transformations of aziridines to 1,2-diamines, 2-oxazolidinones, and benzodiazepines have been developed. Previous work in the Pinhas group showed that an aziridine could be reacted with lithium iodide, iron carbonyl, and trimethylamine oxide to yield a 1,2-diamine. This reaction has been extended to include various amine oxides, several different aziridines, and a variety of metal carbonyls. A novel synthesis of 1,2-diamines has been developed, in which, an aziridine is treated with an iminium salt in the presence or absence of lithium iodide. This reaction has also been extended to include various iminium salts and several different aziridines. The stereochemistry and mechanism of both of these reactions have also been investigated. It has also been discovered that when an aziridine is treated with lithium iodide and then quenched with carbon dioxide, the product is an oxazolidinone. This reaction has been examined using several different aziridines. The reaction is catalytic in lithium iodide. In fact, a catalytic amount of lithium iodide improves the stereoselectivity of the reaction. It has been determined that hexamtheylphosphoramide can be added to the reaction mixture to improve the regiochemistry of the product oxazolidinone. When an aziridine is treated with a phenyl-substituted iminium salt, the expected 1,2-diamine is generated. However, when an aziridine is treated with a phenyl-substituted amine oxide or gem-aminoether, a benzodiazepine is produced. A mechanism is proposed based on the preliminary results.

Committee: Dr. Allan Pinhas (Advisor) Subjects: Chemistry, Organic

Doctor of Philosophy (PhD), University of Toledo, 2011, College of Medicine

Benzodiazpines (BZs) are clinically useful anxiolytics, sedatives, and anticonvulsants. Their mechanism of action is positive allosteric modulation of γ-aminobutyric acid type A (GABAA) receptors, the main inhibitory neurotransmitter receptors in the mammalian central nervous system. Long-term administration of BZs and other positive allosteric GABAA receptor modulators, neurosteroids, barbiturates, and ethanol can lead to physical dependence manifested by a characteristic withdrawal syndrome. A common mechanism proposed to contribute to this withdrawal syndrome is functional up-regulation of L-type voltage-gated calcium channels (L-VGCCs). Our lab models BZ dependence using a 1-week oral treatment of rats with flurazepam (FZP) followed by 1 or 2 days of withdrawal. This treatment paradigm resulted in a near doubling of voltage-gated Ca2+ currents in hippocampal CA1 neurons. Enhanced L-VGCC-mediated Ca2+ influx may activate Ca2+/calmodulin-dependent protein kinase II (CaMKII), which potentiated excitatory synaptic function in CA1 neurons correlating with expression of FZP withdrawal anxiety. The current studies tested three hypotheses: 1) GABAA receptor modulators directly inhibit recombinantly expressed L-VGCCs containing neuronal α1 subunits, Cav1.2 or Cav1.3; 2) L-VGCC subunit expression is increased in the rat hippocampal CA1 region; and 3) CaMKII enhances CA1 excitatory synaptic function via activation and autophosphorylation at Thr286 and/or enhanced localization to the postsynaptic density (PSD). The findings suggested that while the barbiturate pentobarbital and ethanol directly inhibit L-VGCCs at clinically relevant concentrations, the concentrations of BZs and neurosteroids required to inhibit recombinant L-VGCCs were likely too high to be clinically relevant. Interestingly, Cav1.2 channels were more sensitive to inhibition by pentobarbital and FZP and were less sensitive to inhibition by the L-VGCC benzothiazepine (BTZ) antagonist, diltiazem, than Cav1.3 (open full item for complete abstract)

Committee: Elizabeth Tietz Ph.D. (Committee Chair); Zi-Jian Xie Ph.D. (Committee Member); David Giovannucci Ph.D. (Committee Member); Scott Molitor Ph.D. (Committee Member); Bryan Yamamoto Ph.D. (Committee Member) Subjects: Neurosciences

Doctor of Philosophy in Biomedical Sciences (Ph.D.), University of Toledo, 2009, College of Medicine

Fast inhibitory synaptic transmission is mainly mediated by GABAA receptors (GABAARs), a key determinant of neuronal excitability in the central nervous system. Modulation of GABAAR expression and function has important consequences to control neural activity at both cell and network levels. GABAARs are clinically important targets for a number of anti-convulsant, anxiolytic and sedative-hypnotic agents and are implicated in several prominent neurological and mental disorders including epilepsy, anxiety, cognitive deficits, schizophrenia, depression and drug abuse. In this dissertation, we investigated the effects of hypoxia on GABAAR function in rat primary cortical neurons. Maximal GABA currents were significantly reduced immediately following 4 h hypoxia and after 48 h recovery without a change in the EC50 for GABA. 2 h or 8 h hypoxic exposure did not cause significant effects on GABA currents. 4 h hypoxia also affected GABAAR benzodiazepine pharmacology. Maximal potentiation of GABA currents by diazepam increased immediately following 4 h hypoxia, while zolpidem enhancement of GABA currents increased after 48 h recovery. Hypoxic exposure resulted in a depolarizing shift in the equilibrium potential for chloride at 24 h recovery after 4 h hypoxia. The L-type voltage-gated calcium channel (L-VGCC) antagonist, nitrendipine, during hypoxia or control treatment, not only prevented the reduction of GABA currents after hypoxia, but also increased the control currents over baseline. Nitrendipine also prevented the increase in zolpidem potentiation of GABA currents after 48 h recovery and the depolarizing shift in chloride reversal potential. These data demonstrated that the effects of hypoxia on GABA currents, zolpidem pharmacology and chloride reversalpotential require L-VGCC activation. Calcium entry through L-VGCC activated the calcium/calmodulin-dependent phosphatase, calcineurin (CaN). Inhibition of CaN activity acutely reversed the reduction of GABA currents immed (open full item for complete abstract)

Committee: L. John Greenfield M.D., Ph.D. (Committee Chair); Elizabeth Tietz Ph.D. (Committee Member); David Giovannucci Ph.D. (Committee Member); Linda Dokas Ph.D. (Committee Member); Zi-Jian Xie Ph.D. (Committee Member) Subjects: Neurology; Physiological Psychology