Abstract Low population density in rural areas makes it difficult to deliver services to people with mental health problems and nonmedical prescription opioid abuse remains a problem in the United States. The purpose of this cross-sectional study was to determine whether a parent's socioeconomic status affected care opportunities for children 12 to 17 years of age and whether bipolar disorder increased the likelihood of substance abuse in those children. The theory of reasoned action/planned behavior provided the framework for the study. Secondary data from the Interuniversity Consortium for Political and Social Research 36361 data system, specifically the National Survey on Drug Use and Health 2014, were collected that included information about the socioeconomic status of adolescents and their parents. Cross-sectional analysis was used to analyze data. The first research examined the extent to which bipolar disorder influenced opioid abuse in those between the ages of 12 and 17. There was a nonsignificant association between the variables: chi-square probability values (p > 0.05) for mental health difficulties and ever-used pain relievers non-medically. There was a significant association between mental health and emotional difficulties at p < 0.05. The second research question examined whether a parent's socioeconomic status impacted the level of care opportunities for those 12 to 17 years' old in relation to bipolar disorder in rural communities. Using multivariate logistic regression analysis, no significance was found between level-of-care opportunities and a parent's socioeconomic status. The findings of this study have potential to bring about social change by increasing clinician skills related to intervention planning related to opioid abuse in rural communities among adolescents with bipolar disorder.

Chronic pain syndrome continues to be a national health concern among all medical specialties. It has an impact on the entire health care system and if current trends continue, the economic impact alone will exceed 100 billion dollars. In 2014, 254 million prescription opioids were written in the United States. During this time, an increase in prescription opioid related deaths was seen, with approximately 20,101 deaths occurring in 2015. Properly trained clinicians across the health care system are needed to achieve successful patient outcomes, while reducing cost, morbidity, and mortality. The purpose of the scholarly project was to develop a comprehensive, opioid-specific, expert reviewed and evidenced-based educational module for health care clinicians of all specialties. Using the guidelines offered by the Center for Disease Control in 2016, the content of the project was developed with a primary focus on the clinical processes, pharmacological properties, and appropriateness of opioids in the treatment of chronic pain. The educational module was disseminated to 10 experts in the field of pain management and family practice. Each of them was asked to evaluate the educational module and evaluate it from an expert standpoint via Likert-scale evaluation form. The data revealed a median score of 4.5 out of 5 for most all categories, demonstrating the project's ease of use, evidenced-based content, and its ability to further expand the knowledge of clinicians. The project will be presented to stakeholders and state representatives for wide spread distribution. Educating health care professional over the continuum will ensure effective social change and shift the current trends in prescription opioid related mortality and morbidity.

Background: Correctional nurses make up a large part of the corrections workforce and have increasing responsibility for making decisions about patient care in the opioid dependent incarcerated patients. The National Commission on Correctional Health Care (NCCHC) has intoxication and withdrawal standards that advocate individuals entering a correctional facility under the influence or undergoing withdrawal from opioids have their therapy continued, or a plan for appropriate referral for treatment. The NCCHC standard that incarcerated opioid dependent inmates have their therapy continued or a plan for appropriate referral for treatment is not adhered to consistently, as the current process lacks organization. Purpose: The purpose of this quality improvement project was to develop an adult opioid dependence referral for treatment tool for opioid use dependent patients to be utilized by correctional nurses and providers working in the corrections intake medical facility with posttest evaluation. Theoretical Framework: Peplau’s nurse-patient relationship theory was used. Methods: A descriptive, exploratory design was utilized. Results: A majority of the nurses acknowledged the usefulness of the Nursing Opioid Referral for Treatment Algorithm (NORTA) in facilitating the adult opioid dependence referral process. In addition, of the 20 nurses surveyed, 18 nurses agreed that the NORTA tool was relevant to the adult opioid dependence referral process. Most claimed that the NORTA facilitated the opioid dependence referral process. Conclusion: The pain management algorithm is an effective referral method for opioid users as it contributes to patient safety through safe prescription and careful assessment of patient risk regarding opioid use. The findings from this project may impact nursing practice by identification of a new organized approach to enhance the current opioid dependence referral process.

Indiana University-Purdue University Indianapolis (IUPUI) / Mu opioid receptors (MORs) mediate the analgesic and rewarding effects of opioids. Most research has focused on MORs in GABAergic neurons; however, MORs are also in glutamatergic neurons and their role in opioid-related behaviors was unclear. Our lab previously showed that MORs inhibit glutamate transmission from vesicular glutamate transporter 2 (vGluT2)-expressing thalamostriatal synapses. The behavioral relevance of MORs in vGluT2-expressing neurons was unknown; therefore, I utilized a conditional MOR knockout mouse with MORs deleted in vGluT2-expressing neurons (MORflox-vGluT2cre). MORflox-vGluT2cre mice have disrupted opioid reward, locomotor stimulation, and withdrawal, compared to cre-recombinase negative littermate controls. However, other MOR-mediated behaviors, including opioid-induced antinociception, alcohol reward, and palatable substance consumption are intact. MORs are expressed in vGluT2 neurons in several reward-related brain regions, including the thalamus and lateral habenula (LHb). To determine whether MORs in these brain regions modulate opioid-related behaviors, an adeno-associated viral (AAV) vector encoding cre-recombinase was stereotaxically injected into the thalamus or LHb of MORflox mice to specifically delete MORs in these brain regions. Opioid reward and locomotor stimulation remained intact in both thalamic and LHb MOR knockout mice; however, basal locomotor activity was increased in LHb MOR knockout mice. Sucrose consumption was also intact in LHb MOR knockout mice. Interestingly, in LHb MOR KO mice opioid withdrawal-induced paw shakes were increased, while withdrawal-induced jumping was completely ablated. Our lab previously showed that MORs inhibit glutamate transmission from the anterior insular cortex (AIC), which is disrupted by in vivo alcohol exposure. To determine the role of AIC MORs, AIC MORs were deleted with AAV vectors. AIC MOR knockout mice had intact opioid, sucrose, and alcohol reward, but had increased basal locomotor activity. MORs in glutamatergic neurons are critical mediators of opioid reward; however, the specific glutamatergic neurons mediating the rewarding effects of opioids remains to be determined.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第18859号 / 医博第3970号 / 新制||医||1008(附属図書館) / 31810 / 京都大学大学院医学研究科医学専攻 / (主査)教授 渡邊 直樹, 教授 渡邉 大, 教授 松原 和夫 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DGAM

京都大学 / 0048 / 新制・課程博士 / 博士(農学) / 甲第19024号 / 農博第2102号 / 新制||農||1030(附属図書館) / 学位論文||H27||N4906(農学部図書室) / 31975 / 京都大学大学院農学研究科食品生物科学専攻 / (主査)教授 伏木 亨, 教授 保川 清, 教授 金本 龍平 / 学位規則第4条第1項該当 / Doctor of Agricultural Science / Kyoto University / DFAM

No description available.

Opioid use disorder is a chronic, relapsing disease, with more than 85% of individuals experiencing a relapse episode within one year. One common reason patients relapse is due to intense cravings, which are defined as the compulsive urge to use the drug. In fact, craving was recently added to the DSM criteria for substance use disorder diagnosis. Counterintuitively, cravings intensify over the course of extended abstinence, especially in response to drug-paired cues, a phenomenon known as “incubation of craving”. This contributes to difficulty in maintaining long-term sobriety. The mesocorticolimbic reward pathway facilitates self-administration and cue-induced incubation of craving for drugs of abuse and natural rewards, such as sucrose. In particular, the shell sub-region of the nucleus accumbens is a critical brain region involved in context/cue-mediated reward seeking. In the experiments described here, we utilized an incubation of craving model, in which male and female rats self-administered opioids (morphine or heroin) or sucrose for 10 days. Sucrose served as an important control for delineating drug-induced changes from those caused in response to natural rewards, which are not the intended target of potential treatments. Reward delivery was paired with a cue light that was later used to elicit craving. After self-administration, rats underwent brief (one day) or extended (30 days) forced abstinence. One or 30 days later, they were returned to the chambers for a “cue test”, in which responses on the previously reward-associated lever triggered cue presentation, but no contingent reward. We used this model to further delineate behavioral and affective changes that accompany increased opioid craving in late abstinence, as well as molecular alterations underlying craving in rats that did not undergo a cue test. We found an opioid-specific behavioral signature in which peak opioid craving is accompanied by decreased grooming and hyperactivity in both sexes. We tracked the female estrous cycle throughout, as these fluctuations in reproductive hormones (akin to the menstrual cycle) are shown to affect cocaine- and nicotine-related behaviors. We found no differences between females in different phases of the estrous cycle in terms of self-administration, nor craving. RNA sequencing of the nucleus accumbens shell revealed robust changes in gene expression that occurred across extended abstinence, though the genes themselves were altered in a sex- and reinforcer-specific manner. In general, we found many behavioral and molecular changes that were unique to sex and reinforcer (sucrose versus opioids). This is promising in terms of identifying opioid-specific targets that are unlikely to affect the natural reward system in both sexes. Changes in gene expression in the brain are mediated in part by epigenetic processes that influence access of transcriptional machinery to DNA. Acetylation of histone tails, the proteins around which DNA is wrapped and packaged in the nucleus, have been identified as permissive marks that facilitate long-lasting changes in transcriptomics in response to environmental insults. Opioids promote increased acetylation, which may contribute to some of the reported changes here. We tested the efficacy of JQ1, a treatment that interferes with the read-out of opioid-induced acetylated marks, at attenuating heroin self-administration. When administered as an intracerebroventricular microinjection on self-administration day 11, JQ1 had no effect on subsequent heroin taking in either sex, suggesting that it may not be suitable as a systemic treatment at the dose given. These studies lay the groundwork for future studies to administer other treatments throughout abstinence, based on the opioid-specific genes and pathways identified here, to reduce cue-induced heroin craving and the accompanying suite of behaviors in males and females. / Psychology

Background: The opioid epidemic in the United States has been on the rise. Acute exacerbations of chronic pancreatitis (AECP) patients are at higher risk for Opioid Use Disorder (OUD). Evidence on OUD's impact on healthcare utilization, especially hospital re-admissions is scarce. We measured the impact of OUD on 30-day readmissions, in patients admitted with AECP from 2010 to 2014. Methods: This is a retrospective cohort study which included patients with concurrently documented CP and acute pancreatitis as first two diagnoses, from the National Readmissions Database (NRD). Pancreatic cancer patients and those who left against medical advice were excluded. We compared the 30-day readmission risk between OUD-vs.-non-OUD, while adjusting for other confounders, using multivariable exact-matched [(EM); 18 confounders; n = 28,389] and non-EM regression/time-to-event analyses. Results: 189,585 patients were identified. 6589 (3.5%) had OUD. Mean age was 48.7 years and 57.5% were men. Length-of-stay (4.4 vs 3.9 days) and mean index hospitalization costs ($10,251 vs. $9174) were significantly higher in OUD-compared to non-OUD-patients (p < 0.001). The overall mean 30-day readmission rate was 27.3% (n = 51,806; 35.3% in OUD vs. 27.0% in non-OUD; p < 0.001). OUD patients were 25% more likely to be re-admitted during a 30-day period (EM-HR: 1.25; 95%CI: 1.16–1.36; p < 0.001), Majority of readmissions were pancreas-related (60%), especially AP. OUD cases’ aggregate readmissions costs were $23.3 ± 1.5 million USD (n = 2289). Conclusion: OUD contributes significantly to increased readmission risk in patients with AECP, with significant downstream healthcare costs. Measures against OUD in these patients, such as alternative pain-control therapies, may potentially alleviate such increase in health-care resource utilization.

Background: Capsule endoscopy (CE) is a non-invasive imaging modality designed to evaluate various small bowel pathologies. Failure to reach the cecum within the battery lifespan, termed incomplete examination, may result in inadequate testing and possibly delayed therapy. Several studies have attempted to evaluate the association between CE completion and opioid use. However, their results are conflicting. The aim of this meta-analysis is to evaluate the previously published literature on the association between opioid use and CE completion. Methods: We performed a comprehensive literature search in PubMed, PubMed Central, Embase, and ScienceDirect databases from inception through June 1, 2018, to identify all studies that evaluated the association between CE completion and opioid use. We included studies that presented an odds ratio (OR) with a 95% confidence interval (CI) or presented the data sufficient to calculate the OR with a 95% CI. Statistical analysis was performed using the comprehensive meta-analysis (CMA), version 3 software. Results: Five studies with a total of 1,614 patients undergoing CE in the inpatient (IP) and outpatient (OP) setting were included in this study, 349 of which had an incomplete CE (21.6%). The pooled OR for CE completion is 0.50 (95% CI: 0.38-0.66, I2=36.9%) in opioid users compared to non-users. No publication bias was found using Egger's regression test. Conclusions: Our results indicate that patients on opioids are significantly less likely to have a complete CE examination compared to non-users. To our knowledge, this study represents the first meta-analysis to assess this association.