Thesis (PhD)--Macquarie University, Division of Linguistics & Psychology, Department of Linguistics, 2003. / Bibliography: p. 397-424. / Introduction -- Models of shared decision-making in medicine -- Framing the study -- The analytic goals of modelling agency -- The context of treatment decision-making in HIV -- Agency and alignment -- Study conclusions and implications. / The quality of doctor-patient communication has been shown to influence treatment uptake, adherence and effectiveness in HIV medicine and elsewhere. Increasingly, it is considered essential that doctors and patients jointly participate in decisions concerning treatment. There is a growing body of literature describing joint decisionmaking and suggesting guidelines for its practice. Few of these studies, however, relate their descriptions of medical decision-making as a social process to the ways in which patterns of verbal interaction realize or foreclose on joint decision-making. -- Dominant models of medical decision-making view shared decision-making as a midpoint between enlightened paternalism and informed choice. Based on a corpus of HIV consultations audio-recorded in Sydney in the late 1990s, this thesis argues that it can be better modelled as a particular type of social process, which differs across a number of dimensions from other styles of medical decision-making, specifiable as contextual parameters of meaning. The thesis then identifies ways in which specific discursive practices realize these contextual parameters. -- A major component of the thesis focuses on agency, and a model is presented in the form of a socio-semantic network, drawing on work by van Leeuwen (1996) and others, which relates a range of grammatical features, not only transitivity patterns, to ways of construing social agency. The thesis then considers the way in which doctors and patients mobilise these and other resources for bringing together potentially conflicting points of view in framing and articulating treatment decisions. Here I draw on notions of mutual alignment (e.g., Goffman 1981) but expand the analysis of what is aligned to account for speakers' implicit discourse orientation, as well as more overt markers. -- Findings emphasise the relationship between representing and enacting agentive roles; the importance of doctors and patients mutually projecting each other's voices; and the variable and iterative character of shared decision-making. The research demonstrates how doctors and patients negotiate a complex, interactionally and symbolically mediated agency, and shows that patients often take the lead in developing more collaborative decision-making practice. There are still institutionally and socially determined limits to the degree of control patients may exercise within the consultation, many of which are of course well founded. / Mode of access: World Wide Web. / xvii, 533, [22] p. ill

[Truncated abstract] Background: This thesis examines pharmacotherapy use in the secondary prevention of coronary heart disease. It includes antiplatelet agents, beta-blockers, statins and ACE inhibitors, all shown in landmark clinical trials and meta-analyses to reduce the risk of cardiac events in patients with known coronary disease. Underuse of effective preventive therapies represents a lost opportunity to reduce mortality and morbidity. Overseas studies have shown significant underuse of effective therapies at the time of hospital discharge following an acute event and later in ambulatory care. Australian data on prescribing practices following an acute coronary event and, ongoing use in ambulatory care are sparse. Aims: The aim of this thesis was to quantify the prescription of known effective therapies at the time of hospital discharge following an acute coronary event and ongoing use in ambulatory care. A secondary aim was to identify barriers to optimal secondary prevention thus providing an evidential basis to recommend change. Methods: This was an observational study of a cohort of post-MI patients admitted to a tertiary and affiliate hospital in Perth, Western Australia. The continuum of care from the treatment plan at discharge through to the treatment regimen and risk factor management 12 months post-MI was examined. The intermediate step, communication about the treatment plan with the patient and the primary health care provider was also examined. The study involved a review of hospital medical records and follow-up questionnaires to patients and their general practitioners at 3 and 12 months post-MI. All post-myocardial patients were included in the analysis of prescriptions at discharge. The follow-up study included patients 80 years and younger with no terminal conditions. Patient interviews at 3 months and interviews and focus groups with key hospital staff provided qualitative data to inform the quantitative data.

Thesis (MFamMed)--Stellenbosch University, 2015. / ENGLISH SUMMARY: Background: Sub Saharan Africa is home to approximately two thirds of the world’s population of HIV positive individuals. In view of the socioeconomic challenges of the region governments have provided antiretroviral therapy free to improve chances of survival among patients. However, adherence to antiretroviral therapy is recognised as more important in predicting patient survival. Aim: The study aimed to describe the prevailing factors that influence adherence to antiretroviral therapy. Methods: The study design was carried out using three methods of data collection. Focus group discussions, semi structured interviews and a questionnaire format. Setting: This study has been conducted among adult patients attending the Dora Nginza Hospital Adult wellness clinic. Results: The methods highlighted factors that influence antiretroviral therapy revealing psychosocial factors – lack of family support, not wanting to take medicines in front of people outside the home; patient factors – co morbidities that disturb patient adherence to therapy, a lack of trust in the patient-care giver relationship, fear of the drug side effects; socioeconomic factors – patients’ inability to afford food or transport costs to clinic appointments. In the semi structured interviews, 25% of patients self reported on poor adherence while in the questionnaire 5% of patients reported poor adherence. In assessing the effect of adherence to therapy on CD4 count and viral load there was a general increase in CD 4 count and a drop in viral load indicating clinical improvement in patients on therapy. Recommendation: There is a need for clinicians developing a health relationship with patients to facilitate adherence. The interventions designed to help patients in adherence to therapy should involve the patients in question in the designing of these interventions. Conclusion: Adherence monitoring is an important aspect of managing patients on antiretroviral therapy. The factors highlighted are similar to findings of other studies in similar contexts i.e. resource poor settings. / AFRIKAANSE OPSOMMING: Opsomming nie beskikbaar.

Thesis (MNutr (Interdisciplinary Health Sciences. Human Nutrition))--Stellenbosch University, 2008. / Introduction: More than half a million children worldwide die from the Human Immunodeficiency Virus (HIV) and Acquired Immunodeficiency Syndrome (AIDS) each year. In Uganda, HIV/AIDS is a major cause of infant and childhood mortality. Although the government of Uganda, through various strategies, has increased access to antiretroviral drugs (ARVs), resulting in national scaling up of accessibility to antiretroviral therapy (ART), initiation of ART in resource-limited areas remains a challenge due to constraints such as the absence of or limited number of CD4 machines and related laboratory constraints. Further scaling up of ART for children would be greatly strengthened by increased access to laboratory services for CD4 counts or the introduction of alternative indicators or guidelines for the initiation of ART. Aim: This study therefore set out to investigate, through the analysis of retrospectively collected data, whether anthropometric indices (wasting - weight for height; underweight - weight for age; and stunting - height for age) could provide a useful alternative guide when deciding about initiation of ART in children aged 2-12 years in the absence of sophisticated clinical and laboratory support. Methods: The study was conducted at the Mildmay Centre, an HIV/AIDS specialist centre located in Kampala, Uganda. Parameters such as the age at which children had been initiated onto ART, duration on ART, World Health Organisation (WHO) and Centre for Disease Control (CDC) disease stages at time of initiation, anthropometry at time of initiation, CD4% staging at time of initiation, support received from food aid programmes, referral to other health centres as a result of malnutrition and care-giver nutrition education/counselling were all determined retrospectively from clinical records. Results: It was found, based on CDC (2000) growth reference charts, that of the total number of children who took part in this study (N=125), 98.4% were mildly wasted, 52.8% mildly underweight and 75.2% mildly stunted when they were initiated onto ART. Of the children, who had WHO disease staging documented - 40% (N=50), the majority - 86% (N=43) were in WHO disease staging II and III during initiation of ART. and 96% (N=48) were mildly wasted. However, the relationship between WHO disease staging and wasting, underweight, and stunting at initiation of ART in children at the Mildmay centre was not significant. The relationship between CD4% and underweight or stunted children was also not significant. It was established however, that in the absence of CD4 laboratory parameters (since CD4% is vital in the initiation of ART in children) as is the case in resource limited areas, anthropometric indices (moderate to severe wasting, weight for height -W/H) could be used concurrently with CDC and WHO disease staging to initiate ART in children. However, it is important to note that anthropometric indices on their own cannot be used as a guide for initiating ART in children. Conclusion: Anthropometric status alone cannot be used to accurately determine when to initiate ART in children 2-12 years.

The objective of this study was to assess levels of HAART adherence and factors affecting it. An observational, analytic, cross-sectional and quantitative study using IMB model was conducted on a randomly selected 349 HIV/AIDS patients on a HAART regimen. Data collection was done by interviewing respondents using a structured questionnaire. Both descriptive and inferential statistics used in the study. Only 80.2% of the total sample population reported a HAART adherence rate of more than or equal to 95% in this study. The findings highlight the need for on-going educational, informational and other interventions to address the knowledge, motivation and adherence behavioural skills of patients in order to improve the current levels of HAART adherence behaviour. The study also suggested the need for research into objective measures of adherence as well as longitudinal studies on adherence behaviour because strict adherence to treatment is a long-term process and not a one-time activity. / Health Studies / M.A. (Public health)

M.A. (Public Management and Governance) / This study starts with an introduction and background, and this is followed by a statement of the research problem, research rationale, research objectives, research design, research methodology and the data collection methods. A list of acronyms will be provided, as well as an overview of chapters, conclusions, and acknowledgements. “Around 5.7 million in 2009 had contracted HIV and AIDS and in the preceding year 250,000 South Africans died due to HIV/AIDS related diseases. All age categories and gender are prone to contracting the disease and the resultant loss of life has had a devastating effect on the workforce. Death due to this disease has caused loss of income and family disintegration” (Sottile 2013:2). In 2010, some 280,000 South Africans died of HIV/AIDS. In the decade up to 2010, between 42% and 47% of all deaths among South Africans were HIV/AIDS-related deaths (Sottile 2013:2). Mlambo et al (2011:1) further say that “The Human Sciences Research Council estimates that 10.9% of all South Africans have HIV/AIDS. Additionally, the Central Intelligence Agency estimates that 310,000 individuals died in South Africa from HIV/AIDS in the year 2009”. A study in 2003 made a comparison on two scenarios, an HIV/AIDS scenario and a no-HIV/AIDS scenario and this was based on the annual growth rates between 2002 and 2015. The finding was that “real growth in GDP would be 0.6% lower than if there were no HIV/AIDS, but per-capita growth in GDP would be 0.9% higher. Growth in population would have been 1.5% lower, and growth of the labour force would be 1.2% lower, but the unemployment rate would be 0.9% lower as well” (Avert.Org 2010:2). Different HIV/AIDS prevention strategies are being implemented in South Africa. The focus in this study is on male medical circumcision (hereafter MMC), which is the removal of all or part of the foreskin on the penis. It can either be performed surgically in hospitals or at initiation schools. Initiation schools perform the procedure as a traditional rite of passage from boyhood to manhood, and this is referred to as traditional male circumcision (TMC). This practice has up till now been performed purely for traditional or religious purposes, but it can no longer be viewed only as such. It should, instead, also be seen as a measure to curb the spread of the HIV/AIDS pandemic. A number of observational studies (which will be referenced later) found that circumcised men had smaller chances of contracting HIV infection compared with uncircumcised men...

The introduction of antiretroviral drugs (ARVs) in 1996 transformed the treatment of HIV and AIDS, improving the quality and greatly prolonging the lives of many infected people. HIV (Human Immunodeficiency Virus) is the virus that is believed to cause AIDS. AIDS (Acquired Immune Deficiency Syndrome) is the collection of illnesses or symptoms that ultimately results in death. Antiretroviral (ARVs) drugs or Highly Active Antiretroviral Therapy (HAART) is the treatment that has been applied to combat the HI virus in a bid to slow down the progression of AIDS and ultimately prolong the life of the infected individual. The study aimed to explore and describe the factors contributing to adherence and non-adherence to ARVs in individuals on treatment. A sample of 81 individuals who have been on ARV and HAART treatment for six months or more was used. The methodology used was exploratory-descriptive and the data obtained was quantitative in nature. A biographical questionnaire and questionnaire with questions aimed at ascertaining the possible factors that contribute to individuals either adhering to or defaulting on their treatment, such as side effects and cost of treatment, was administered. The data obtained was analysed by means of descriptive statistics and frequency counts. The results of the study showed that the sample had a fairly high level of adherence. The factors that could undermine adherence were identified as lack of support, as familial and health provider support acts as a motivator to adhere; substance abuse as it can lead to forgetting to take treatment; unemployment and poverty, as these can lead to an inability to return for follow up clinic visits or failure to have food to take with the pills; and the type of treatment regimen whereby the more complex the treatment is the more likely it is that adherence will be difficult to maintain. Suggestions were made as to future research involving antiretroviral therapy (ART). Finally the limitations as well as the value of the research were outlined.

This study has focused on the synthesis of truncated analogues of the hydroxyethylene dipeptide isosteres, such as Ritonavir®, currently in clinical use as HIV-1 protease inhibitors. The reactions of pyridine-2- and quinoline-2-carbaldehydes with methyl acrylate, in the presence of 1,4-diazabicyclo[2.2.2]octane (DABCO) or 3- hydroxyquinuclidine (3-HQ) as nucleophilic catalysts, have afforded a series of Baylis- Hillman adducts, acetylation and cyclisation of which have provided access to a series of indolizine-2-carboxylate esters. The carboxylic acids, obtained by base-catalyzed hydrolysis of these esters, have been coupled with various protected (and unprotected) amino compounds using the peptide coupling agent, 1,1’-carbonyldiimidazole (CDI), to afford a series of indolizine-2-carboxamides as indolizine-based truncated Ritonavir® analogues in quantitative yield. Aza-Michael reactions of pyridine-3-carbaldehydederived Baylis-Hillman adducts with various amino compounds have provided access to a range of pyridine-based products as mixtures of diastereomeric aza-Michael products. The assignment of the relative stereochemistry of the aza-Michael products has been established using 1-D and 2-NOESY experiments and computer modelling techniques. Computer modelling studies have also been conducted on selected aza-Michael products using ACCELRYS Cerius2 software, followed by interactive docking into the HIV-1 protease receptor site, using AUTODOCK 4.0. The docking studies have revealed hydrogen-bonding interactions between the enzyme and the synthetic ligands. Saturation Transfer Difference (STD) NMR experiments have also indicated binding of some of the aza-Michael products to the HIV-1 protease subtype C enzyme, thus indicating their binding and possible inhibitory potential.

The present study was undertaken to determine the effects and possible mechanism of action of cimetidine in cancer and Alzheimer’s disease (AD). Throughout this study emphasis is placed on free radical levels since the magnitude of the relationship between diseases and the levels of free radicals vary from one disease to another. Studies were carried out to examine the effect of cimetidine on free radical levels using superoxide formation and lipid peroxidation as indicators of free radical levels. The experiments revealed that addition of cimetidine, especially in high concentrations (0.5 and 1.0 x10-6 M) significantly inhibited WHCO6 cancer cell growth rather than cancer cell growth, as no normal control was available. Free radical formation as well as hydroxyl radical formation were reduced in the deoxyribose assay. In addition, cimetidine exhibits properties of binding to metals such as copper and iron. To maintain consistency in the experiments, a WHCO6 (Wits Human Carcinoma of the Oesophagus) cell line was used to investigate the effect of cimetidine in cancer. Neurodegeneration was induced in the rat brain using neurotoxins such as cyanide to investigate the relationship between cimetidine in AD. A decrease in cancer cell growth was accompanied by a concomitant decrease in the levels of free radicals and lipid peroxidation, suggesting that the growth-inhibitory effects of cimetidine on WHCO6 cancer cells in vitro may be due to free radical scavenging properties. This proposal was further strengthened by determination of free radical levels in the rat brain. After treatment with neurotoxins to induce neurodegeneration, the levels of free radicals in the rat brain suggest that addition of cimetidine reduces free radical levels in the rat brain in a dosedependent manner. Further experiments were done in an attempt to uncover the underlying mechanism by which cimetidine exhibits free radical scavenging properties. Metal binding studies were done using electrochemical, HPLC and UV/Vis studies. The results show that cimetidine binds iron and copper. These metals have been implicated in free radical production via the Fenton reaction. By binding with cimetidine the metals become unavailable to produce free radicals and hence cimetidine indirectly reduces the formation of free radicals. The final experiment was the determination of cimetidine as a hydroxyl radical scavenger in the deoxyribose assay. Cimetidine was shown to act as a potent hydroxyl radical scavenger, thereby confirming its activity as a free radical scavenger. In addition, cimetidine protects against damage to the deoxyribose sugar, a component of DNA. Whilst there are many theories that explain the therapeutic role of cimetidine in degenerative disease, the actual mechanism of the role of cimetidine is emphasized as a free radical scavenger. Regardless of the mechanism of action, cimetidine does inhibit tumour growth according to this study and also reduce free radical levels in neurodegeneration, which suggests a role for cimetidine as a possible additive in treatment of patients with such disease states. These findings have important clinical implications, and needs to be investigated further.

The project has focused on the preparation of several series of compounds designed as potential HIV-1 integrase inhibitors. Various 2-nitrobenzaldehydes have been reacted with two activated alkenes, methyl vinyl ketone (MVK) and methyl acrylate, under Baylis-Hillman conditions to afford α-methylene-β-hydroxylalkyl derivatives in moderate to excellent yields. The reactions were conducted using the tertiary amine catalysts, 1,4-diazabicyclo[2.2.2]octane(DABCO) or 3-hydroxyquinuclidine (3-HQ) with chloroform as solvent, and yields were optimised by varying the catalyst, reagent concentrations and the reaction time. Reductive cyclization of the Baylis-Hillman adducts via catalytic hydrogenation, using 10% palladiumon-carbon catalyst in ethanol, afforded quinoline and quinoline N-oxide derivatives. In some cases “acyclic” reduction products were also isolated. Reaction of the Baylis-Hillman MVK adducts with HCl, has resulted in effective nucleophilic (SN’) displacement of the hydroxyl group to afford allylic chloride derivatives. Direct substitution of these chloro derivatives by secondary or primary amines, followed by catalytic hydrogenation gave quinoline derivatives containing a 3-aminomethyl substituent. The Baylis-Hillman ester adducts obtained from reaction with methyl acrylate were treated directly with various amines to give diastereomeric conjugate addition products. Reactions with piperazine gave N,N’-disubstituted piperazine products. The piperidine derivatives have been dehydrated to give cinnamate esters in moderate yields. The products, which have all been satisfactorily characterised by elemental (HRMS) and spectroscopic (1- and 2-D NMR) analysis, constitute a “library” of compounds for in silico and in vitro studies as potential HIV integrase inhibitors.