Background: In Kazakhstan, opioid substitution therapy (OST) has been a controversial topic since its introduction in 2008. Aim: To examine and analyse factors influencing approach towards OST among OST patients, opioid-dependent drug users who could re-consider engagement in this therapeutic method, as well as attitudes of selected key organisations and their representatives. Methods: A survey method complemented by semi-structured individual and group interviews has been selected. One hundred respondents participated in the study between October and December 2015. The first group consisted of 46 OST patients. The second group consisted of 54 respondents who met criteria for opioid dependence. This group included patients of residential treatment centres, former OST patients and current injecting drug users. Key persons were interviewed about their attitudes. Results: Patients receiving OST, with the average treatment duration of 29.4 months, reported improved health, improved social functioning and financial well-being, as well as reduction of their involvement in crime. This group showed better results in all examined categories. Most (80 %) were satisfied with the treatment, even though a number of shortcomings have been reported. All OST patients considered necessary to expand the availability...

Background: The consequences of continued opioid abuse among patients treated with opioid substitution therapy (OST) are serious and can result in abnormal cardiovascular function, overdose, and mortality. Conflicting evidence exists that both implicates and refutes the role of chronic non-cancer pain (CNCP) as a major risk factor for continued opioid abuse within the addiction treatment setting. This thesis aims to 1) evaluate the impact of chronic pain on the treatment outcomes of patients with opioid addiction receiving OST, 2) determine whether a clinical or inflammatory profile exists to distinguish pain in this population, 3) explore the sources of heterogeneity in previous studies examining this question, 4) determine the best therapy for patients with chronic pain, and 5) evaluate the most effective treatment for opioid addiction. We anticipate chronic pain to be an important predictor of continued opioid abuse such that patients with comorbid pain will require careful consideration when managed on OST. Methods: We systematically reviewed the literature to determine the impact of pain in opioid addiction patients receiving methadone maintenance treatment (MMT). We determined the clinical and inflammatory profile of MMT patients using data from the Genetics of Opioid Addiction (GENOA) research collaborative between the Canadian Addiction Treatment Centres (CATC) and the Population Genomic Program. GENOA is a prospective cohort study aimed to determine the genetic, biological, and psychosocial determinants of treatment prognosis for opioid addiction patients receiving MMT. GENOA recruits patients ≥ 18 years of age meeting the DSM-IV criteria for opioid dependence. All GENOA participants are receiving MMT for the management of opioid addiction. Baseline data from the GENOA pilot study (n=235) were used to evaluate the impact of pain on illict opioid use behaviour and determine the clinical and inflammatory profile of patients with comorbid pain. We explored sources of heterogeneity in previous studies using data from the full-phase GENOA study (n=444), examining the prognostic value of different pain measures for predicting illicit opioid use. We then performed a multiple treatment comparison of all opioid substitution and antagonist therapies in efforts to determine the best intervention for improving treatment outcomes for patients with comorbid pain. We lastly determined the most effective treatment for opioid addiction by performing a network meta-analysis using data from a systematic review of opioid maintenance therapy trials. Results: Our initial systematic review confirmed a lack of consensus in the literature, whereby some studies suggest pain increases risk for illicit opioid use and other studies suggest pain has no effect on substance use behaviour. Findings from the analysis of GENOA pilot data confirmed chronic pain to be an important predictor of sustained opioid abuse and also showed patients with pain to have elevated Interferon-Gamma. Using data from the GENOA prospective cohort study we determined the Brief Pain Inventory (a commonly used pain measurement in pervious studies) to be highly sensitive with poor prognostic value. Our final reviews propose 1) there is limited evidence to suggest any OST is superior for managing patients with comorbid pain, and 2) heroin and high-dose methadone are the most effective treatments for improving treatment retention. The final systematic review and network meta-analysis in this thesis also highlights a major problem in the treatment of opioid use disorders, primarily the lack of consensus as to what outcomes matter for determining success in patients with addiction. Conclusion: Patients with comorbid pain and addiction are at high-risk for continued opioid abuse and should be managed closely by clinicians administering OST. Contention in the previous literature likely resulted from the use of pain measurements with poor prognostic value. No OST demonstrated superiority for managing patients with chronic pain. While our findings indicate heroin is the most effective treatment across multiple endpoints, we use this thesis to provide readers with 1) a sense of the feasibility issues associated with heroin administration, 2) a summary of the limitations of this evidence base, and 3) recommendations for how to improve the addiction trials’ design for future research. / Thesis / Doctor of Philosophy (PhD)

Background: Despite the many harms and limited efficacy of opioids in managing chronic noncancer pain (CNCP), they are commonly prescribed for these patients in North America. One of the harms associated with prolonged opioid use is opioid use disorder (OUD); however, the risk of addiction is uncertain. We systematically reviewed observational studies to establish the prevalence of (OUD), and to explore factors associated with OUD in patients with CNCP. Methods: We searched MEDLINE, EMBASE, CINAHL, Cochrane Library, and PsycINFO from inception to December 2018 to identify studies that explored the prevalence of OUD or risk factors for OUD in patients with CNCP. Two specialists in addiction medicine reviewed each potentially eligible study, blinded to results, to ensure their outcome met DSM-5 criteria for OUD. We pooled estimates of OUD across eligible studies using random-effects models. When possible, we pooled estimates of association with OUD for all independent variables reported by more than one study. Results: Twenty-two studies reported the prevalence of OUD, and six studies reported the association of 36 factors with OUD in patients with CNCP. The pooled prevalence of OUD was 20% (95% CI: 15% to 25%); however, we found evidence for small study effects (interaction p<0.001). When restricted to larger studies (≥900 patients), the pooled prevalence of OUD was 5.8% (95% CI: 2.8% to 9.5%; moderate certainty evidence). The prevalence of OUD was not associated with level of certainty of OUD criteria, under- or overestimation of instruments compared to DSM-5 criteria, severity of OUD, or risk of bias (interaction p values ranged from 0.34 to 0.92). Moderate certainty evidence demonstrated an association between OUD and male sex (OR 1.50 [95% CI: 1.05 to 2.14]; absolute risk increase (ARI) 2.7% [95% CI: 0.3% more to 5.8% more]), current smokers (OR 1.63; [95% CI: 1.25 to 2.12]; ARI 3.3% [1.3% more to 5.7% more]), and a history of mental health disorders (OR 1.49 [95% CI: 1.17 to 1.89]; ARI 2.6% [95% CI: 0.9% more to 4.6% more]). Low certainty evidence demonstrated an association between OUD and younger age (OR for every 10-year decrement, 1.60 [95% CI: 1.11 to 2.30]; ARI, 3.2% for every 10-year decrement [95% CI: 0.6% more to 6.6% more]). Moderate certainty evidence suggested no association between OUD and a history of alcohol abuse/dependence (OR 1.32 [95% CI: 0.84 to 2.07]; ARI 1.7% [95% CI: 0.9% less to 5.5% more]), and low certainty evidence suggested no association between OUD and a history of drug abuse (OR 1.51 [95% CI: 0.75 to 3.02]; ARI 2.7% [95% CI: 1.4% less to 9.9% more]). Conclusion: Moderate certainty evidence suggests that 6% of CNCP patients prescribed opioids will develop OUD. Younger men who smoke, with a history of mental health disorders, are at higher risk. Additional research is needed to establish the association between OUD and a history of drug or alcohol abuse. / Thesis / Master of Science (MSc) / Opioids are commonly prescribed for patients with chronic pain that is not due to cancer; however, long-term opioid use inevitably leads to physical dependence and may result in addiction. Prior studies have reported extremely variable rates of opioid use disorder (OUD) following prescription for chronic noncancer pain, ranging from less than 1% to more than 50%, which has led to considerable confusion. My systematic review found moderate certainty evidence that the prevalence of OUD following prescription for chronic pain is 5.8% (95% CI: 2.8% to 9.5%). Patients who were younger, current smokers, males, and had a history of mental health disorders, had a higher risk of developing OUD. These findings will help support shared care decision-making between patients with chronic pain considering opioid therapy and their healthcare providers.

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Heroin dependence, which is escalating within South Africa, has become a symbol of the social disorder of the times - associated with materialism, poverty, crime, the problems of a society in transition, the disadvantaged, and the inner cities. However, that is not to say that all those who misuse heroin develop a problem or become dependent. In reality, only a small minority of heroin users develop a dependence, but for those who do it can result in unpleasant and potentially terrifying experiences/consequences, that can often be extremely difficult to escape from. That is not to say that recovery from dependence to heroin is not possible. Indeed, contrary to the beliefs of many people, the reality is that many people do eventually recover. Despite the vast sums of money devoted to treatment intervention of heroin dependants in the South Africa and worldwide, the processes by which recovery occur remain fairly unclear. Moreover, relatively little is known about the contribution of interventions and processes in facilitating such recovery. The statistical and content analysis of the data revealed that one of the most important factors identified in allowing successful behaviour modification and promoting recovery was psychosocial and pharmacological intervention, which seemed to produce a range of positive effects that facilitated natural healing processes. However, a range of other factors alongside intervention were also important in promoting behaviour modification. This study has provided important information, from forty recovering heroin dependants themselves, on the many factors that are important in achieving abstinence, in allowing recovery to be maintained in the longer term, and in potentially allowing an eventual exit from heroin dependence. A number of difficulties encountered in intervention were also identified. The statistical findings of the study support the `maturing out' hypothesis of heroin dependence (c² = 16.841; r = 0.001; df = 3). Ethnicity, highest level of education, employment status, marital status, biological parents' marital status or whether biological parents were deceased or not did not relate to any of the identified behavioural indices associated with heroin dependence recovery. A framework for the development of a contextual heroin dependence recovery model is also discussed. / Psychology / (M.A.(Psychology))

Heroin dependence, which is escalating within South Africa, has become a symbol of the social disorder of the times - associated with materialism, poverty, crime, the problems of a society in transition, the disadvantaged, and the inner cities. However, that is not to say that all those who misuse heroin develop a problem or become dependent. In reality, only a small minority of heroin users develop a dependence, but for those who do it can result in unpleasant and potentially terrifying experiences/consequences, that can often be extremely difficult to escape from. That is not to say that recovery from dependence to heroin is not possible. Indeed, contrary to the beliefs of many people, the reality is that many people do eventually recover. Despite the vast sums of money devoted to treatment intervention of heroin dependants in the South Africa and worldwide, the processes by which recovery occur remain fairly unclear. Moreover, relatively little is known about the contribution of interventions and processes in facilitating such recovery. The statistical and content analysis of the data revealed that one of the most important factors identified in allowing successful behaviour modification and promoting recovery was psychosocial and pharmacological intervention, which seemed to produce a range of positive effects that facilitated natural healing processes. However, a range of other factors alongside intervention were also important in promoting behaviour modification. This study has provided important information, from forty recovering heroin dependants themselves, on the many factors that are important in achieving abstinence, in allowing recovery to be maintained in the longer term, and in potentially allowing an eventual exit from heroin dependence. A number of difficulties encountered in intervention were also identified. The statistical findings of the study support the `maturing out' hypothesis of heroin dependence (c² = 16.841; r = 0.001; df = 3). Ethnicity, highest level of education, employment status, marital status, biological parents' marital status or whether biological parents were deceased or not did not relate to any of the identified behavioural indices associated with heroin dependence recovery. A framework for the development of a contextual heroin dependence recovery model is also discussed. / Psychology / (M.A.(Psychology))