Heroin use and dependency is a growing concern within South Africa, individuals face difficulty in remaining abstinent from the use of heroin due to constant relapse. The opioid antagonist known as the naltrexone pellet implant offers an alternative form of aid to relapse prevention in the recovery and abstinence from heroin dependency. This qualitative study explored the subjective experiences and perceptions of heroin dependent individuals, that made use of the naltrexone pellet implant. This study was rooted in the interpretive, qualitative paradigm where a phenomenological research design was used. Participants were selected using a purposive, snowball sampling technique and four individuals who had made use of the naltrexone pellet implant for the aid in heroin dependency for a minimum of three-months were interviewed. Interpretative Phenomenological Analysis (IPA) was used to extract recurrent themes across participants. The findings suggested that the use of the naltrexone pellet implant was beneficial in the aid for relapse prevention from heroin use. Furthermore, the exploration of difficulties that were faced in remaining abstinent, the attempt to make use of the naltrexone pellet implant and the physical and psychological aspects regarding the use of this alternative method of remaining abstinent were explored in this study. / Psychology / M.A. (Psychology (Research Consultation))

The susceptibility of adolescents to chemical addiction has become a major international concern. Approximately 25% of people in Central Asia and Eastern Europe who inject chemical substances are under the age of 20 years (Youth at the United Nations, 2006), while up to 75% of unintentional injuries among adolescents in America are related to substance abuse (Page & Page, 2003:196). On the national level, approximately 25% of adolescents under the age of 20 are involved in substance abuse (Western Cape Department of Social Services and Poverty Alleviation Transformation Plan, 2006:13). Focusing on the Western Cape, a report from the South African Epidemiology Network (2007:3) highlights that the youngest patient in in-patient treatment was nine years of age, and among 2 798 persons who received in-patient treatment, 27% were under the age of 20, more than any other age group in treatment. Treatment of adolescent chemical addiction should include preparation for treatment, treatment, and also aftercare services to ensure that the addicted adolescent develops skills to maintain sobriety (Meyer, 2005:292-293). Section Six of the South African Prevention and Treatment of Drug Dependency Act (1992) prescribes that chemically addicted persons should have access to professional aftercare services to ensure that treatment is not terminated prematurely. The motivation for this study was based on the fact that, despite this statutory requirement, the Western Cape Drug Forum (2005:3) identified the need for the development of aftercare services in 2005, indicating the lack of focus on aftercare as part of treatment. This concern was confirmed by practitioners in the field of adolescent chemical addiction and findings resulted from previous research regarding relapse experiences of chemically addicted adolescents (Van der Westhuizen, 2007:129-130). / Social Work / D. Phil. (Social Work)

Against the background of an increase in the demands for treatment of adolescent chemical addiction, as well as the persistently high relapse rate, the significant impact on the development and well-being of chemically addicted adolescents needs to be considered by the social work profession, in order to plan effective intervention strategies. The purpose of this research study was to explore and describe the experiences of chemically addicted adolescents who had relapsed after in-patient treatment. Subsequently, the researcher aimed to generate guidelines and recommendations for social workers, in order to prevent relapse. A qualitative research approach was employed. The researcher made use of descriptive, exploratory and contextual research designs. The study was conducted at adolescent in-patient treatment centres in the Western Cape, South Africa. Data was collected through semi-structured interviews. Interviews were tape-recorded and transcribed, and field notes were taken to record the data. The sample selected from the population of chemically addicted adolescents in the Western Cape who relapsed after in-patient treatment was selected through the purposive sampling technique. Tesch's framework for data analysis (in Creswell, 2003) was employed, and data verification was conducted through Guba's model (in Krefting, 1991:214-222). The research results, concluding guidelines and recommendations are being disseminated by means of this written report. / Social Work / M. Diac. (Social Work)

Against the background of an increase in the demands for treatment of adolescent chemical addiction, as well as the persistently high relapse rate, the significant impact on the development and well-being of chemically addicted adolescents needs to be considered by the social work profession, in order to plan effective intervention strategies. The purpose of this research study was to explore and describe the experiences of chemically addicted adolescents who had relapsed after in-patient treatment. Subsequently, the researcher aimed to generate guidelines and recommendations for social workers, in order to prevent relapse. A qualitative research approach was employed. The researcher made use of descriptive, exploratory and contextual research designs. The study was conducted at adolescent in-patient treatment centres in the Western Cape, South Africa. Data was collected through semi-structured interviews. Interviews were tape-recorded and transcribed, and field notes were taken to record the data. The sample selected from the population of chemically addicted adolescents in the Western Cape who relapsed after in-patient treatment was selected through the purposive sampling technique. Tesch's framework for data analysis (in Creswell, 2003) was employed, and data verification was conducted through Guba's model (in Krefting, 1991:214-222). The research results, concluding guidelines and recommendations are being disseminated by means of this written report. / Social Work / M. Diac. (Social Work)

A descriptive survey to identify factors influencing relapse of psychiatric outpatients in the rural communities of the Eastern Cape was undertaken. A questionnaire was used to collect data from family caregivers who were relatives of psychiatric patients receiving their monthly medications from two rural clinics. Data were analysed using the Statistical Package for Social Sciences (SPSS) version 17. A total number of 92 family caregivers participated. Respondents reported side effects of psychotropic drugs, poor family role, poor referral system, lack of home visits, non-compliance and stigmatization as major factors contributing to relapse of psychiatric outpatients. Active involvement of caregivers in follow up care of their relatives is effective in fostering collaboration between the psychiatric hospitals and patients with the common goal of relapse avoidance. It is recommended that adequate provision of resources in conjunction with health education is effective in enhancing collaboration towards prevention of relapse in psychiatric patients. This would promote team work among patients, caregivers and health care providers. / Public Health / M.A. (Public Health)

Thomas G. Brown, Ph.D., co-directeur de recherche / Objectifs : La capacité en matière de prise de décisions des récidivistes de conduite avec capacités affaiblies (CCA) semble les distinguer des non-contrevenants, particulièrement dans des situations ambiguës à haut risque, telles que la CCA. Cette étude exploratoire vise à vérifier l’hypothèse selon laquelle les récidivistes de CCA (R) auraient une moins bonne capacité de prise de décisions et une plus faible réponse de conductibilité électrodermale par anticipation à la tâche Iowa Gambling Task (IGT) que les non-contrevenants (C). Méthode : Vingt-trois récidivistes et 24 non-contrevenants ont été recrutés. Leur âge moyen (± É.T.) était 44.17(10.03) et 37.29 (10.60) ans respectivement. Les participants devaient être âgés de 18 ans ou plus, et avoir eu deux condamnations pour CCA ou plus pour le groupe R, et zéro CCA et un permis de conduire pour le groupe C. Les participants ont effectué I’IGT, une tâche neurocognitive de prise de décisions comprenant 100 sélections de cartes divisées en cinq blocs pour les analyses. On a comparé la performance du groupe R versus le groupe C à l’aide d’une ANOVA à mesures répétées [2 (groupe) x 5 (blocs)]. On a évalué la performance durant les blocs 1 & 2 (décisions dans l’ambiguïté) et blocs 3-5 (décisions sous haut risque) en utilisant des tests t post-hoc. Finalement, on a mesuré leur réponse de conductibilité électrodermale (RCEA) durant l’IGT. Résultats : L’ANOVA à mesures répétées des blocs 1 à 5 a révélé un effet significatif de l’interaction groupe par bloc, F(1,45)=5.28, p=.03, état carré =.11. Les tests t post hoc ont révélé une différence significative entre les groupes pour la combinaison des blocs 3 à 5, t(45) = 3.38, p = .002. Un effet d’interaction significatif a été détecté pour la RCEA des récidivistes de CCA versus celle des non-contrevenants, F(8,160)=2.33, p=.02, état carré =.10. Conclusion : Les récidivistes de CCA performent moins bien que les non-contrevenants à l’IGT. Ils persistent à prendre des décisions basées sur le potentiel de gains immédiats et négligent donc les risques de pertes. Ceci suggère qu’ils ont des déficits en matière de prise de décision, ce qui, en tant que groupe, les différencie des non-contrevenants. Une difficulté en matière de prise de décisions pourrait expliquer en partie le comportement impulsif fréquemment associé au récidivisme de CCA. Finalement, puisque les analyses de RCEA manquaient de puissance statistique, il est possible que de plus grands échantillons puissent permettre d’observer des différences entre les groupes de participants dans l’analyse de RCEA. / Objectives: Poor decision making in ambiguous high-risk situations, such as driving while impaired (DWI) by alcohol, may differentiate DWI recidivists from non-offenders. In this study, we test the hypothesis that DWI recidivists (R) will exhibit poorer decision-making performance on the Iowa Gambling Task (IGT), and in line with the Somatic Marker Hypothesis, weaker anticipatory somatic activation (using skin conductance response as index) than non-offenders (C, comparison group). Methods: DWI recidivists and non-DWI control drivers were recruited, [R (n=23) and C (n=24), mean ages (± SD) 44.17(10.03) and 37.29 (10.60) years respectively]. Participant selection criteria included ≥ 18 years old and ≥2 DWI convictions for group R and 0 DWI convictions lifetime and a driver’s license for group C. The participants performed the IGT, a decision-making neurocognitive task containing 100 card selection trials that we divided into 5 blocks for analyses. A 2 (group) x 5 (blocks) repeated measures ANOVA was used to compare group R performance on the IGT versus group C, followed by post hoc independent t-tests on aggregated blocks 1-2 (decision under ambiguity) & 3-5 (decision under high risk) to identify the source of group X block significant interactions. Two 3 (group) x 5 (blocks) repeated measures ANOVAs (for good decks and for bad decks) were used to compare the aSCR of groups C and R. Results: ANOVA repeated measures on blocks 1 to 5 produced a significant effect of group by block interaction F(1,45)=5.28, p=.03, partial ƞ2 =.11. Post hoc t-tests on aggregated blocks 3 to 5 were statistically significant, t(45) = 3.38, p = .002. A significant group x block interaction effect was found for good decks aSCR, F(8,160)=2.33, p=.02, partial ƞ2 =.10 . Conclusion: DWI recidivists performed more poorly than controls on the IGT, persistently making decisions based on potential immediate gains and neglecting associated loss risks and long-term outcome. This suggests they have reduced neurocognitive decision-making capacities distinguishable from the general population. While DWI recidivists’ behaviour appears as impulsive, these results suggest that their behaviour pattern involves decision-making difficulties. Larger sample sizes may be needed to detect a between-group effect in the aSCR analyses, as they were considerably underpowered.

Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal.

Treatment of patients with multiple sclerosis (MS) and development of new therapies have been challenging due to the disease complexity and slow progression, and the limited sensitivity of available clinical outcomes. Modeling and simulation has become an increasingly important component in drug development and in post-marketing optimization of use of medication. This thesis focuses on development of pharmacometric models for characterization and quantification of the relationships between drug exposure, biomarkers and clinical endpoints in relapse-remitting MS (RRMS) following cladribine treatment. A population pharmacokinetic model of cladribine and its main metabolite, 2-chloroadenine, was developed using plasma and urine data. The renal clearance of cladribine was close to half of total elimination, and was found to be a linear function of creatinine clearance (CRCL). Exposure-response models could quantify a clear effect of cladribine tablets on absolute lymphocyte count (ALC), burden of disease (BoD), expanded disability status scale (EDSS) and relapse rate (RR) endpoints. Moreover, they gave insight into disease progression of RRMS. This thesis further demonstrates how integrated modeling framework allows an understanding of the interplay between ALC and clinical efficacy endpoints. ALC was found to be a promising predictor of RR. Moreover, ALC and BoD were identified as predictors of EDSS time-course. This enables the understanding of the behavior of the key outcomes necessary for the successful development of long-awaited MS therapies, as well as how these outcomes correlate with each other. The item response theory (IRT) methodology, an alternative approach for analysing composite scores, enabled to quantify the information content of the individual EDSS components, which could help improve this scale. In addition, IRT also proved capable of increasing the detection power of potential drug effects in clinical trials, which may enhance drug development efficiency. The developed nonlinear mixed-effects models offer a platform for the quantitative understanding of the biomarker(s)/clinical endpoint relationship, disease progression and therapeutic response in RRMS by integrating a significant amount of knowledge and data.

Le craving est considéré comme une composante centrale de l’addiction, potentiellement impliquée dans les processus de rechute, et influencée par de nombreux facteurs. Les études ayant examiné le lien entre craving et rechute montrent cependant des résultats contradictoires. Ces divergences pourraient s’expliquer par les limites méthodologiques rencontrées pour évaluer le craving de façon rétrospective ou pour l’induire expérimentalement en laboratoire. La méthode EMA (Ecological Momentary Assessment) utilise des technologies mobiles afin d’évaluer les sujets dans leur environnement naturel et de récolter des données en temps réel. Cette approche est particulièrement intéressante pour étudier les fluctuations rapides du craving, capturer l’influence des variables environnementales, ainsi que pour examiner le lien prospectif entre plusieurs variables. L’objectif général de cette thèse était d’utiliser la méthode EMA afin d’examiner en vie quotidienne le craving, ses modérateurs, et son lien avec l’usage de substances chez des sujets dépendants débutant une prise en charge pour une addiction à une substance. L’analyse de la littérature révèle que la majorité des études EMA examinant le craving concerne le tabac et l’alcool, et que peu d’études ont examiné ce phénomène pour des substances illégales. La partie expérimentale de cette thèse a permis de 1) démontrer la faisabilité et la validité de la méthode EMA chez des sujets dépendants, quelle que soit la substance de dépendance (tabac, alcool, cannabis ou opiacés), 2) montrer un lien prospectif unidirectionnel entre l’intensité du craving et l’usage de substances pour les 4 groupes de substances, et 3) mettre en évidence une augmentation du craving face à des stimuli conditionnés (cues) rencontrés en vie quotidienne, augmentation d’autant plus importante qu’il s’agissait de cues individuels (personnels à chaque sujet). Cette étude démontre l’intérêt de la méthode EMA dans l’étude des addictions, souligne le rôle du craving dans les processus de rechute, et encourage le développement de protocoles d’extinction de la réactivité aux cues centrés sur des cues individuels propres à chaque sujet. / Craving is a central component of addiction, involved in relapse process and under the influence of many factors. However, studies examining the link between craving and relapse have revealed some contradictory results. These inconsistencies could be due to limits encountered to assess craving in laboratory or clinical settings. Ecological Momentary Assessment (EMA) methods use mobile technologies to assess subjects in their daily life, and collect data in real time. EMA is particularly well suited to assess fluctuations of craving, capture influence of environmental moderators, and examine prospective link between variables. The objective of this thesis was to use EMA to examine craving, its moderators, and its link with substance use in daily life among substance-dependent outpatients evaluated at treatment intake. Review of the literature revealed that majority of EMA studies examining craving concerned tobacco and alcohol, but only few examined illegal substances. The experimental part of this thesis 1) demonstrated that EMA methods are feasible and provide valid data in individuals with dependence for different types of substances (tobacco, alcohol, cannabis, opiates), 2) showed a prospective unidirectional association between craving and subsequent substance use in the 4 groups of substances, and 3) confirmed that conditioned stimuli (cues) encountered in daily life are associated with an increase of craving intensity, and showed that individual personalized cues elicit a more robust effect on craving compared to standard cues. These results highlight the relevance of using EMA methods to study addiction, suggest that craving has a key place in the relapse process, and encourage to develop tailorised extinction protocols centered on individual cues rather than standard non-specific cues.

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