published_or_final_version / Sociology / Master / Master of Philosophy

Introduction: Opioid poisoning has been rapidly increasing in the past decade, and has been driven in large part due to increases in opioid prescribing. This has been accompanied by intervention efforts aimed at preventing and reversing opioid poisoning through naloxone prescription programs. Current literature have not quantified the economic burden of opioid poisoning. Understanding this information can help inform these efforts and bring light to this growing problem. In addition understanding various determinants of increased costs can help to identify the types of populations more likely to have greater costs. Main Objectives: The objectives are 1) to quantify the economic burden of opioid poisoning, 2) to evaluate differences in costs, LOS, and in-hospital mortality depending on opioid type, 3) to identify opioids most likely to result in hospitalization for opioid-related ED visits and 4) to determine differences in the odds of admission to various hospital admission categories with respect to opioid type. Methods: A cost-of-illness approach was used to estimate the economic burden of opioid poisoning. Direct costs and prevalence estimates were obtained from nationally representative databases. Other sources of direct costs were obtained from the literature. Indirect costs were measured using the human capital method. Differences in costs, LOS, and in-hospital mortality were measured through generalized linear models using the National Inpatient Sample in 2009 from the Healthcare Cost and Utilization Project. The Drug Abuse Warning Network database was used to evaluate opioids most likely to result in hospitalization and to evaluate the likelihood of different opioids to cause admission into different types of hospital settings. Results: Opioid poisoning resulted in an economic burden approximately $20.4 billion dollars in 2009. Productivity losses were associated with 89% of this total. Direct medical costs were associated with $2.2 billion. Methadone was associated with the greatest inpatient costs and LOS, while heroin was associated with a greater likelihood of in-patient mortality compared to prescription opioids. Heroin, methadone, and morphine were associated with the greatest odds of hospitalization. Among admitted patients, methadone, morphine, and fentanyl were each associated with the greatest odds of ICU admission compared with other opioids. Conclusions: Opioid poisoning results in a significant economic burden to society. Costs, length of stay, in-patient mortality and the odds of hospitalization and admission type depend on the type of opioid involved. The results from this study can be used to inform policy efforts in providing interventions to reduce opioid poisoning and help focus efforts on populations at highest risk for increased costs.

Magister Artium (Social Work) - MA(SW) / Heroin usage is on the increase in the Western Cape province of South Africa owing to globalization and to increased access to the drug in this province. The goal of this study is to explore the experiences of coloured heroin users in the Metro South area of , which stretches from Simons Town and Muizenberg to Retreat, Lavender Hill, Grassy Park, Parkwood and Wynberg. These individuals have been found to congregate in the Wynberg CBD. The overarching theoretical framework for the purpose of this research is social constructionism and symbolic interactionism, using a qualitative means of inquiry. Snowball sampling was used to recruit prospective participants and data was collected by means of in-depth interviews, with a semi structures interviewing schedule. The questions informed the subsequent themes and categories that arise from the data collection process. Snowball sampling was employed in this case, a non-probability sample, in which participants were recruited via key informants. The sample distribution included 13 participants, 10 of which were heroin users (5 female, 5 male) and the remaining 3 were key informants which contributed to triangulation of the data. In terms of the findings, participants spoke of mostly being involved in intimate relationships, which according to participants had dual benefits. For female participants intimate relationships offered a form of protection on the often dangerous streets of Wynberg and for certain males, intimate relationships offered an opportunity to fund their habit, by trading their female partners to perform sexual favors for money to acquire heroin. While the study found females were mainly involved in trading sexual favors for money, heterosexual males were also implicated in having sexual relations with homosexual men for money. Furthermore, the study found that heroin users in Wynberg represented a surrogate family, where, because of their lifestyle, they were disconnected from their own family. This family surrogate was found to be supportive, caring to a large extent, shared a living space, protective of each other and shared a common language and understanding.

Zhu Jian-hui. / "July 2000." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2000. / Includes bibliographical references (p. 174-215). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

Thesis. 1976. M.C.P.--Massachusetts Institute of Technology. Dept. of Urban Studies and Planning. / Microfiche copy available in Archives and Rotch. / Bibliography: leaves 72-74. / by Regionald [sic] Joseph Williams. / M.C.P.

It is increasingly recognised that chronic exposure to opioids has been associated with neuropsychological impairment during both active use and following a period of abstinence. The overall objective of this thesis was to review the relevant prior literature in a systematic manner and subsequently to describe the effects of chronic exposure to prescribed and illicit opioids using an ambispective cohort study design. A systematic literature review was conducted to identify if chronic (defined as a period for more than 3 months) exposure to opioids (prescribed and/or illicit) was associated with measurable neuropsychological deficits. This review was conducted accordingly to the Meta-analysis of Observational Studies in Epidemiology (MOOSE) and the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) guidelines. The results were subsequently described within three cognitive domains of intelligence, executive function and memory and learning. Out of a total of 905 articles extracted between 1964 and 2009, 49 articles were considered appropriate for selection and review. Studies of current and abstinent chronic opioid users (illicit heroin users, patients prescribed methadone for illicit opioid dependence and patients taking opioids as part of the management of chronic pain) have identified performance deficits in measures of executive functioning and memory. These have included impairments within the domains of cognitive and motor impulsivity, strategic planning, cognitive flexibility, attention and memory. However other studies found no clear deficits when comparing the performance of healthy controls. The literature suggested that these neuropsychological deficits may be subject to at least partial recovery following initiation of methadone or total withdrawal from any opioids.This review also highlighted several methodological issues that affect the reliability, validity and clinical relevance of the results obtained. Subsequently a two year ambispective cohort design study was conducted which tested representative opioid exposed participants and healthy controls. Cohorts of participants with validated histories of illicit heroin use (HEROIN, n=24), stabilised methadone maintenance (METHADONE, n=29), chronic opioid prescriptions for pain (CHRONIC PAIN, n=28) and controls (HEALTHY CONTROL, n=28) were recruited. The study was designed to test neuropsychological performance in the HEALTHY CONTROL and CHRONIC PAIN groups on one occasion; and for the HEROIN and METHADONE groups on three and two occasions respectively. The intention was to describe neuropsychological performance in the HEROIN group under conditions of stable illicit heroin use, in controlled opioid withdrawal and when subsequently stabilised on methadone. For the METHADONE group, participants were tested twice, six months apart, to test for changes induced by chronic exposure to methadone. Eligible, screened and consented individuals were tested on nine tests from the CANTAB test battery. Data were analysed using univariate or repeated measures ANCOVA with a between subjects factor of GROUP. Further a priori subgroup analyses were conducted using (1) a two-group factor reflecting DEPENDENCE status and (2) a two-group factor reflecting INJECTING status separately as between subject factors. The homogeneity of variance across groups in repeated-measures design ANCOVAs was assessed by the Mauchly Sphericity Test. NART, age in years, SIMD, total Fagerström score, years in education and past alcohol use in years were used as covariates. A significance level of p<0.01 was applied due to multiple testing, in addition to the post-hoc Bonferroni correction procedure. On the Cambridge Gambling Task (CGT), HEROIN users placed higher bets earlier and risked more. They also showed increased motor impulsivity, impaired strategic planning and visuospatial memory on the Affective Go-NoGo (AGN), Stockings of Cambridge (SOC), and Delayed Matching to Sample(DMS) respectively. METHADONE users deliberated longer and placed higher bets earlier on the CGT, but did not show a tendency to risk more. METHADONE users were also more inattentive and demonstrated poor strategic planning and visuospatial memory on the Spatial Span (SSP) task. The CHRONIC PAIN participants did not exhibit significant impairment in neuropsychological performance on all the CANTAB tasks. Participants from the HEROIN, METHADONE and CHRONIC PAIN groups did not present with impaired cognitive flexibility. Chronic opioid dependence is associated with neuropsychological impairment reflected in altered performance on measures of risk taking and strategic planning. These data support the hypothesis that these neuropsychological impairments reflect an underlying trait vulnerability to drug taking and/or dependence rather than an effect of chronic exposure to opioids. Notably, motor impulsivity and visuo-spatial memory in HEROIN users improved after three weeks stability with methadone. Methadone use seems to confer improvement in some aspects of neuropsychological performance following cessation of heroin and sustains other deficits during long term stable methadone treatment. Dependence and injecting status do not contribute to the causation or deterioration of the identified neuropsychological impairments. Further long term longitudinal studies to help elucidate cognitive endophenotypes responsible for the components in the initiation, continuation and deterioration of neuropsychological deficits present in an opioid dependent population is necessary.

Protein engineering has been a useful tool in the fight against human diseases. Human insulin was the first recombinant DNA-derived therapeutic protein (Humulin®) approved by the US FDA in 1982. However, many of the early protein drugs were only recombinant versions of natural proteins with no modification of their primary amino acid sequence and most of them did not make optimal drug products mainly due to their short half-life or suboptimal affinity, leading to poor therapeutic efficacy. The difficulty in the large-scale production of some therapeutic proteins was another important issue. In the past three decades, different protein engineering platforms have been developed to overcome the obstacles seen in the first generations of these treatments. With the help of these new techniques, proteins have been purposefully modified to improve their clinical potential. The focus of my dissertation is the engineering of potential protein drugs to make them therapeutically useful and more valuable. Previously, our research group has developed cocaine hydrolases (CocHs) from human butyrylcholinesterase (BChE) for treatment of cocaine addiction and prevention of acute cocaine intoxication. In the first project, CocHs were further engineered to improve their performance, e.g., Fc-fused CocHs with an extended serum half-life. Then, I investigated the potential application of a long-lasting CocH for protection against the acute toxic and stimulant effects of cocaine. In the second project, I investigated the potential inhibition of CocH-mediated cocaine hydrolysis by heroin (3,6-diacetylmorphine) or its initial host metabolite, 6-monoacetylmorphine (6-MAM). The investigation of this possible inhibition was important to determine the in vivo efficacy of CocHs, as heroin is one of the most commonly co-abused drugs by cocaine-dependent individuals, as well as a possible metabolite of CocHs. In the third project, I expressed and characterized the recombinant human UDP-glucuronosyltransferase 1A10 (UGT1A10) enzyme, which can inactivate many therapeutically valuable substances. In the fourth and final project, prostate apoptosis response-4 (Par-4), a tumor suppressor protein, was engineered to have a prolonged duration of action so that it may be more therapeutically valuable for cancer treatment.

Fatal and non-fatal opioid overdoses resulting from opioid induced respiratory depression are a significant problem throughout the world. Whilst the opioid receptor antagonist, naloxone hydrochloride, can effectively reverse opioid overdoses, its use is limited because of the adverse effects it produces. These include severe withdrawal and the reversal of analgesia produced by opioid receptor agonists. In this project, the peripherally acting opioid receptor antagonist, naloxone methiodide, was investigated for its potential to reverse opioid induced respiratory depression without altering centrally mediated effects, such as withdrawal. In the publications presented in this thesis, naloxone hydrochloride and naloxone methiodide were shown to effectively reverse the decreases in respiratory rate produced by the administration of morphine, methadone and heroin in mice. Naloxone hydrochloride and naloxone methiodide also reversed the analgesia produced by these opioid receptor agonist treatments, but only naloxone hydrochloride induced significant withdrawal. The doses of naloxone methiodide required to produce the effects described above were higher than the naloxone hydrochloride doses required. Radioligand binding techniques indicated that this was due to a difference in the affinity of naloxone hydrochloride and naloxone methiodide for µ, δ and κ opioid receptor binding sites. Radioligand binding techniques were also used to confirm that naloxone methiodide, or its metabolites, could not readily cross the blood brain barrier. Therefore, the effects of naloxone methiodide appear to be mediated outside the central nervous system. The final publication aimed to extend our knowledge of opioid induced respiratory depression by utilising new radiotelemetry technology to test the efficacy of naloxone methiodide in rats subjected to a chronic opioid administration regime. This experiment showed that circadian rhythm plays a role in the development of tolerance to the cardiorespiratory effects of continuous and chronic methadone administration, and that naloxone hydrochloride and naloxone methiodide treatment can increase respiratory rate and heart rate after this methadone administration. Therefore, naloxone methiodide can effectively antagonise the peripheral effects produced by opioid receptor agonists. Peripherally acting opioid receptor antagonists should be developed in the future to prevent or treat the adverse effects of opioid receptor agonists. / Thesis (Ph.D.)--Department of Clinical and Experimental Pharmacology, 2004.

<p>Den här uppsatsen har skrivits inom ramen för centralasiatisk säkerhetspolitik ur ett europeiskt perspektiv. Jag har begränsat uppsatsen till att fokusera på narkotika, som på senare år har blivit en kärnfråga i säkerhetspolitiska diskussioner, framförallt i Europa och i USA. Genom att tillämpa ett vidare perspektiv har jag försökt överskrida den eurocentrism, evolutionism, passivisering och viktimisering som finns i litteraturen och de artiklar som jag har studerat. Med den beskrivande tesen: Narkotikans roll i kampen om den globala hegemonin och drömmen om kalifatet, har jag velat belysa narkotikans roll i båda dessa strävanden mot en ny värld. Narkotikans roll som ett maktobjekt kan inte förminskas, varken i européernas kamp om den globala hegemonin eller i de islamistiska extremistgruppernas dröm om kalifatet. Narkotikan har haft en betydande och stimulerande roll i historien, i nutiden och kommer även att ha det i framtiden.</p>

Den här uppsatsen har skrivits inom ramen för centralasiatisk säkerhetspolitik ur ett europeiskt perspektiv. Jag har begränsat uppsatsen till att fokusera på narkotika, som på senare år har blivit en kärnfråga i säkerhetspolitiska diskussioner, framförallt i Europa och i USA. Genom att tillämpa ett vidare perspektiv har jag försökt överskrida den eurocentrism, evolutionism, passivisering och viktimisering som finns i litteraturen och de artiklar som jag har studerat. Med den beskrivande tesen: Narkotikans roll i kampen om den globala hegemonin och drömmen om kalifatet, har jag velat belysa narkotikans roll i båda dessa strävanden mot en ny värld. Narkotikans roll som ett maktobjekt kan inte förminskas, varken i européernas kamp om den globala hegemonin eller i de islamistiska extremistgruppernas dröm om kalifatet. Narkotikan har haft en betydande och stimulerande roll i historien, i nutiden och kommer även att ha det i framtiden.