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In an effort to shift away from the narrow medical model of drug treatment the Advisory Council on the Misuse of Drugs (ACMD), in 1982, introduced the idea of the 'problem drug user' (PDU) and recommended a multi-disciplinary approach in order to meet the increasingly evident multiple and complex problems presented by dependent drug users. However, despite the development of a series of drug strategies (HM Government, 1995; 1998; 2002; 2008; 2010) and vast increases in funding, dependent drug users are still struggling to receive the services they require to address their diverse problems (Neale, 2008; Buchanan, 2010). Through an analysis of in-depth interviews with dependent drug users and their keyworkers this thesis seeks to explain these deficiencies. The author argues that the broad umbrella of drug policy that has adopted a framework of risk-based strategies to regulate and control drugs and drug users has focused on the social and economic costs associated with problem drug use, particularly in relation to the belief that much acquisitive crime is drug-related. Hence, the focus has not been on the problems that drug users have but on the problems they cause. The medical model that has dominated the treatment of addiction has been reinforced, therefore, not only because 'drug addiction' has been described as a chronic and relapsing condition (NTA, 2002), but also because of the wider social control objectives (crime reduction, in particular) that this approach delivers (Lind et al., 2005; Gossop, 2005; Millar et al., 2008). The author examines the implications of these drug policy directions on the treatment journeys of dependent drug users. Firstly, the author demonstrates how the confluence of the health and crime reduction agendas has led to the paradoxical perception of drug users as being 'sick-but-deviant' that has served to exacerbate their stigmatised identities. Secondly, the author suggests that the closer alignment between the drug treatment workforce and the criminal justice system has led to the isolation of drug treatment from wider health and social care services. Together, these two consequences of drug policies have created further barriers to service access and successful recovery, thereby providing an explanation for the unmet need of dependent drug users attending treatment services.

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The aim of this study was to understand how ADHD medication designed as a suitable solution within the prison in terms of treatment. The study had a qualitative disposition and I have used a discourse analysis. My theoretical starting point was extracted from Foucault’s theory about power and knowledge and his discourse concept. The result shows how ADHD portrayed as a factor that is strong linked to crime and various forms of social marginalization. A further result is how the ADHD clients are constructed from untreatable to treatable and how the ADHD medication act as treatment and prevents recidivism. The results show this production of ADHD linked to crime, the ADHD clients as untreatable and the medications as a remarkable treatment method works together to make ADHD medication is a perfect solution to treat criminals and prevent crime.

A Thesis submitted to the Faculty of Health Sciences (Internal Medicine), University of the Witwatersrand, in fulfillment of the requirements for the degree of Doctor of Philosophy. Johannesburg, 2017 / South Africa has the largest ARV treatment programme in the world, wherein highly active antiretroviral treatment (HAART) has improved the health related quality of life (HRQoL) in HIV/AIDS patients. On the contrary, cancers not previously associated with HIV/AIDS (non-Aids defining cancers; NADCs) have been shown to be increasing, compared to the AIDS defining cancers (ADCs). Lung cancer, as a NADC has been documented in the HIV/AIDS population as a leading malignancy. The poor understanding of the association between ARV drugs and lung cancer places a burden on public health, both globally and in South Africa (SA). Furthermore, the deregulation of the cell-cycle is one of the hallmarks of cancer, including lung cancer. The main aim of this study was to elucidate the effects of HAART components Efavirenz (EFV) and Lopinavir/ritonavir (LPV/r) on cell-cycle related genes in an in vitro lung cancer model. To achieve this, cellular based, molecular and Bio-Informatics approaches were employed. First, the cytotoxic effects of EFV (at 4, 13, 26, 50 μM) and LPV/r (at 10, 32, 50, 80 μM), for 24h, 48h and 72h on normal lung fibroblasts (MRC-5) and lung adenocarcinoma (A549) cells, were evaluated using the Alamar Blue (AB) assay. This was then followed by cell-impedance “xCELLigence” real-time cell analysis (RTCA) assay. This was done to determine the effects of EFV (at 4, 13, 50 μM) and LPV/r (at 10, 32, 80 μM) on cell viability, cell death and proliferation. Cell-cycle analysis using propidium iodide (PI) by Fluorescence-activated cell sorting (FACS) was done to quantify DNA present at each of the cell-cycle stages of the cell-cycle in response to ARV treatment. Subsequently, an apoptosis assay using Annexin V FITC and Propidium iodide (PI) dual staining by FACS was carried out to confirm and quantify the ARVs potential apoptotic effects. Then, 4′,6-diamidino-2-phenylindole (DAPI) staining was used to assess changes in nuclear morphology exerted by the ARVs’ effects. A more in depth interrogation of the cell-cycle was performed using a focussed gene array panel of some 84 human cell-cycle related genes. First, total RNA was isolated from both treated and untreated MRC-5 and A549 cells and reverse transcribed to cDNA for use as template in the PCR array reactions. From the array gene expression results, by convention a ±2 fold up-or-down-regulation was used as the basis of target selection. Following this, a real-time quantitative PCR (RT-qPCR) validation of selected genes of interest was done to quantify and confirm the PCR array results. This was followed by in-silico Bio-informatics analysis to map the molecular pathways regulated by the identified targets. For this purpose, STRING, Database for Annotation, Visualization and Integrated Discovery (DAVID), Reactome and Ingenuity Pathway Analysis (IPA) databases were used. Interestingly, double-edged oncogenic properties of both EFV and LPV/r at different concentrations were identified. The proliferative effects of EFV at 4, 13μM and LPV/r at10 μM, were elucidated, while 26, 50μM of EFV, and 32μM of LPV/r had slight inhibitory effects on cell proliferation. LPV/r at concentrations of 50 and 80μM exerted cytotoxic effects on the cells, as demonstrated by the AB and xCELLigence RTCA assays. Cell-cycle analysis using PI staining, particularly showed cell-cycle arrest at 32μM LPV/r, and a shift to G2/M by 13μM EFV, plasma relevant doses, compared to the untreated cells. An increasing apoptosis percentage was observed with increasing LPV/r concentrations, that is, 80μM LPV/r raised the apoptosis percentage almost two-fold compared to 32μM. This was coupled by necrosis, observed in a time-dependant manner. DAPI staining confirmed loss of nuclear integrity post ARV exposure, suggesting that both EFV and LPV/r impose damage to the genomic DNA. To further assess the observed changes in nuclear morphology, the effects of EFV and LPV/r on the expression of an arrayed panel of human cell-cycle genes in cancer and normal lung cells was determined. Significantly differentially expressed targets were identified and further quantified and confirmed by RT-qPCR. Such targets included ATM, p53, cyclin-dependant kinase inhibitors (CDKIs), such as, p21, aurora kinase B (AURKB), Mitotic Arrest Deficient-Like 2 (MAD2L2) and the apoptosis related gene, caspase 3 (CASP3). Bio-Informatics analyses revealed close and direct protein-protein interactions (PPIs) between these targets, notably, with change in interaction between the gene products involved in DNA repair mechanisms, observed between ARV treated and untreated groups, as illustrated by STRING interactions. DAVID, Reactome and IPA analysis showed changes in expression of genes related to stress and toxicity and DNA damage response genes. In particular, ATM, p53 and its downstream targets such as GADD45A (growth arrest and DNA damage inducible alpha) gene were up-regulated by ARV treatment, while cyclin/CDK activity was down-regulated, resulting in reduced cell proliferation. Thus in summary, both EFV and LPV/r altered the expression levels of cell-cycle related genes, influencing overall cellular health, acting to either inhibit or stimulate cell proliferation. This suggests EFV’s and LPV/r’s proliferative and inhibitory roles in the proliferation of lung cells. Moreover, future directions can include the transfection of lung cells with HIV provirus followed by treatment of the cells with the same ARVs under study. This could be substantiated by including HIV positive patient samples on and off ARV drug treatment with lung cancer, including HIV negative patients with cancer as one of the controls. / MT2018

This research addressed change management and learning in a multidisciplinary addictions chronic care environment in order to prepare for shared care planning within an electronic health record. It used a Developmental Work Research approach and was able to use insights from Bernstein’s theory of knowledge structures, Bakhtin’s work on social language and a Critical Realism approach to address weaknesses in the base Activity Theory approach. In these ways problems concerning fragmented, demarcated silo working across clinical and non-clinical addictions services could be examined. The objective of the study was to identify tensions and contradictions in working environments and to engage multidisciplinary workers in a collaborative change laboratory environment via the use of co-configuration and expansive learning. The working group examined past and current practice and were able to formulate new forms of practice, based on the use of a shared care plan tool, to address identified problems and national policy aims. It was able to use the aforementioned theoretical insights to illuminate the multiple utility of the shared care plan tool as a pedagogic device. This enabled the production of new practice possibilities, paradigms and planning to be undertaken, and the consideration of these within the context of ‘real time’ multidisciplinary activity within a forthcoming national IT system. This research has explored, identified and formulated new practice to improve multidisciplinary working between clinical and non-clinical workers across diverse sectors. This will have significant health and cost benefit gains for clients, workers and organisations as well as translating policy aims into effective practice. The next stage will be to manage the roll-out of the forthcoming IT system using the theoretical and methodological developments crafted in this research endeavour.

The Edmonton Drug Treatment and Community Restoration Court (EDTC) diverts substance-addicted offenders from the criminal justice system and provides intensive court supervision, case management, and links to social, employment and education support. This thesis aimed to generate a grounded theory of the process of participant engagement with the EDTC, drawing on staff and participant interviews and observation of EDTC operations. Criteria of engagement included meeting expectations, communicating openly and honestly, and forming bonds. Internal engagement was described as feeling hopeful and willing, and perceiving expectations as helpful rather than controlling. Perceptions underlying internal engagement involved motivation and openness to socialization and trust; feeling engaged resulting in the act of confronting issues rather than avoiding them. The process of engagement was a positive cycle, instigated and perpetuated through interaction with expectations and discipline, realizing and experiencing specific reasons to change, forming trust and accessing internal and external resources to address barriers.

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