Thesis (MPhil)--Stellenbosch University, 2015. / ENGLISH ABSTRACT: While there has been several studies that have been conducted targeting university students at state owned universities in South Africa, specifically on the impact of HIV/AIDS epidemic, no extensive study was conducted to establish what informs adoption of high risk sexual behaviour among university students in the context of HIV, STI and unplanned pregnancy epidemics at any of the state owned South African universities, let alone private universities. In order to address this identified gap in the body of knowledge, a cross-sectional study underpinned by the ‘social norms’ theory was undertaken at a private university in the Gauteng Province, South Africa to establish why undergraduate students engage in high risk sexual behaviour that puts them at risk of contracting HIV, STIs and unplanned pregnancy. Quantitative data was collected from 342 students through a questionnaire and qualitative data was collected from 38 students through the focus group discussions. Findings revealed that early sexual debut, intergenerational sex, multiple and concurrent partners, unprotected sex, sex under the influence of alcohol and illegal drugs and transactional sex constitute high risk sexual behaviour. The study concluded that peer pressure, independence, financial needs, drug and alcohol abuse, fear of being an outcast, need to identify with modernity, lack of individual perception of risk, campus culture and sexual partner influence are the factors influencing the adoption of high risk sexual behaviour on campus. Based on the findings and conclusions, recommendations are provided for the development of an HIV prevention programme on campus that is aimed at mitigating the negative consequences of the HIV/AIDS, STIs and unplanned pregnancy epidemics. / AFRIKAANSE OPSOMMING: Die literatuur toon aan dat daar alhoewel daar wel studies onderneem is ten einde die impak van die MIV epidemie onder studente aan openbare universiteite te bepaal onderneem is, daar nog steeds baie min kennis in hierdie verband bestaan. Die faktore wat ‘n rol vervul in hoërisiko seksuele gedrag onder studente aan hierdie universiteit is grootliks onbekend. Ten einde hierdie gaping te probeer oorbrug is hierdie studie onderneem aan ‘n privaat universiteit in Gauteng provinsie in Suid-Afrika. Die doel van die studie was om vas te stel wat voorgraadse studente motiveer om hoë seksuele gedrag te beoefen, wetende dat hulle hulleself blootstel aan MIV-infeksie en onbeplande swangerskappe. ‘n Steekproef van 342 student is in die studie gebruik en ‘n vraelys is deur hulle voltooi. ‘n Verdere 38 student het deelgeneem aan ‘n fokusgroepbespreking. Resultate toon aan dat studente dikwels meer as een seksuele maat het; dat seks beoefen word terwyl studente onder die invloed van alkohol is; dat seks dikwels onbeskermend plaasvind en dat alle hierdie faktore bydraend is tot hoë blootstelling aan MIV-infeksie. Die studie het verder gevind dat groepsdruk, finansiële probleme, dwelm- en alkoholmisbruik en groepsdruk verdere bydraende faktore tot hoë-risiko gedrag onder studente is. Resultate van die studie is gebruik om aanbevelings te maak vir die ontwikkeling van ‘n MIV-voorkomingsprogram wat daarop gerig is om die oordrag MIV en onbeplande swangerskappe aan die universiteit ( wat in die studie ondersoek is ) te bekamp.

The study sought to identify reasons for non-compliance among a particular medical aid scheme's members and their dependants registered for the asthma disease risk management (DRM) programme. A quantitative descriptive study was undertaken, using postal questionnaires. The research results indicated that most asthma patients were not compliant with the DRM programme because they lacked knowledge about the programme. Asthma patients' compliance with the DRM programme can be enhanced by health providers' and case managers' positive attitudes, better promotion of the programme, and by involving the patients in managing their illnesses. Asthma patients require education about healthy lifestyles, empowering them to successfully manage their condition, preventing asthma attacks and/or hospital admissions. When asthma is well-managed the patients' quality of life and general wellbeing will improve and the medical aid scheme's costs will be contained. / HEALTH STUDIES / MA (HEALTH STUDIES)

Abstract Cardiovascular diseases (CVD), and especially atherosclerotic vascular diseases (ASVD), are the largest cause of morbidity and premature death worldwide. Coronary heart disease (CHD) and cerebrovascular disease (stroke) are common and severe manifestations of ASVD. Atherosclerosis is a chronic inflammatory disease and lipoprotein metabolism disorder. If the regulation of inflammatory process is disturbed, the systemic release of pro-inflammatory mediators, including matrix metalloproteinases (MMPs), may lead to a low-grade systemic inflammation, which is a risk factor for CVDs. MMPs are enzymes that are responsible for the degradation of the extracellular matrix (ECM) during growth and tissue renewal but also in many pathological conditions. These ECM degrading proteases and their regulators play an important role in atherogenesis and subsequent plaque rupture, leading to acute cardiovascular manifestations. The pivotal role of MMPs in atherosclerosis has raised interest in the development of drug therapies targeting these proteases. Doxycycline has inhibitory effects on some MMPs in addition to its antimicrobial properties. The main objective of this thesis project was to investigate the potential of these inflammatory mediators as biomarkers, risk factors, and therapeutic targets in CVD. The special focus was on MMP-8 and its main regulator, tissue inhibitor of matrix metalloproteinase (TIMP)-1. The results of this study show that a high serum MMP-8 concentration indicates an acute cardiac condition and predicts a future CVD event. In addition to MMP-8, MMP-7 is a potential biomarker for incident CVD. The balance between these MMPs and their tissue inhibitor may indicate vulnerability to plaque rupture. Measurement of serum MMP-8 concentration is reliable, anti-invasive and inexpensive and can be done in hospital settings. We also show that regular-dose doxycycline decreases the systemic inflammatory burden in patients with earlier myocardial infarction and is a promising anti-inflammatory therapy in the prevention of CVDs with relatively minor side effects. In conclusion, MMP-8 and TIMP-1 can be considered inflammatory risk markers of CVD events and death, and they can be utilized both for diagnostic and screening purposes. The inhibition of MMP-8 by doxycycline may reduce the systemic inflammatory burden in patients with myocardial infarction. / Tiivistelmä Sydän- ja verisuonisairaudet, erityisesti ateroskleroottiset valtimosairaudet, ovat maailman yleisin sairastuvuuden ja ennenaikaisen kuoleman syy. Sepelvaltimotauti ja aivohaveri ovat ateroskleroottisen valtimosairauden yleisiä ja vakavia ilmenemismuotoja. Ateroskleroosi on krooninen tulehduksellinen sairaus ja lipoproteiiniaineenvaihdunnan häiriö. Jos tulehdustapahtuma häiriintyy, elimistöön vapautuvat tulehdusvälittäjäaineet, kuten matriksin metalloproteinaasit (MMP), voivat aiheuttaa elimistön matala-asteisen tulehduksen, joka on sydän- ja verisuonisairauksien riskitekijä. MMP:t ovat entsyymejä, jotka pilkkovat solunväliainetta kasvun ja kudosten uusiutumisen mutta myös monien tautitilojen yhteydessä. Nämä soluväliainetta hajottavat proteaasit ja niiden säätelijät ovat tärkeässä roolissa ateroskleroottisen plakin muodostumisessa ja repeämisessä, joka johtaa äkillisiin sydäntautitapahtumiin. Matriksin metalloproteinaasien keskeinen rooli ateroskleroosissa on herättänyt kiinnostusta niihin kohdistuvan lääkehoidon kehittämiseen. Doksisykliinillä on joidenkin MMP-entsyymien toimintaa estävä vaikutus antimikrobiaalisten ominaisuuksiensa lisäksi. Tämän väitöskirjatutkimuksen päätavoitteena oli tutkia näiden tulehdusvälittäjäaineiden mahdollisuuksia biomarkkereina, riskitekijöinä ja lääkehoidon kohteena sydän- ja verisuonisairauksissa. Erityinen kiinnostuksen kohde oli MMP-8 ja sen pääsäätelijä ja kudosestäjä, tissue inhibitor of matrix metalloproteinase (TIMP)-1. Tämän tutkimuksen tulokset osoittavat, että seerumin korkea MMP 8 pitoisuus viittaa akuuttiin sydäntautiin ja ennakoi tulevaa sydäntautitapahtumaa. MMP-8:n lisäksi MMP-7 on lupaava sydäntapahtuman biomarkkeri. Näiden matriksin metalloproteinaasien ja niiden kudossäätelijä TIMP-1:n välinen tasapaino voi liittyä ateroskleroottisen plakin haurauteen. Seerumin MMP-8:n mittaus on luotettavaa, kajoamatonta ja edullista, ja mahdollista toteuttaa myös sairaalaolosuhteissa. Näytämme myös, että doksisykliini vähentää elimistön tulehdustaakkaa sydäninfarktin sairastaneilla potilailla ja että se on sydäntautien ehkäisyssä lupaava anti-inflammatorinen lääke, jolla on suhteellisen vähän sivuvaikutuksia. Johtopäätöksenä on, että MMP-8:aa ja TIMP-1:tä voidaan pitää lupaavina sydän- ja verisuonitautien sekä kuoleman biomarkkereina sekä diagnostiikka- että seulontakäytössä. Lisäksi tutkimustulokset osoittavat, että MMP-8:n esto doksisykliinillä voi vähentää elimistön tulehdustaakkaa sydänkohtauksen sairastaneilla potilailla.

Patients with chronic inflammatory conditions such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) experience premature cardiovascular mortality and morbidity compared with the general population. The increased risk of cardiovascular disease (CVD) may in part, result from an interaction between traditional and non-traditional risk factors, modulated by chronic inflammation. The aim of this project was to look at lipid associated biomarkers in patients with SLE/RA and the association between these markers and cardiovascular disease outcomes. We also aimed to study the effect of inflammation reduction on vascular biomarkers. In the first study we examined 168 SLE patients median (IQR) age was 53 (46-61) years and median disease duration 13 (7, 23) years and 56 healthy controls median age 50 (39-60) years. We demonstrated elevated level of oxidised-LDLin SLE patients compared with healthy controls (76 (57, 99) U/l vs 56 (42, 88)U/l P= 0.02). We further explored the association between oxidant stress and premature atherosclerosis as measured by carotid intima media thickness (cIMT) and plaque. In addition to age and systolic blood pressure, oxidised-LDL and urinary 8-isoprostane were significantly and independently associated with cIMTin SLE patients _ coefficient 95%CI [0.00007 (5.29−6, 0.0001) and 0.003 (0.0008,0.004)], respectively. In healthy controls, age was the only independent variable. In the Norfolk Arthritis Register, 1266 patients with early inflammatory polyarthritis (IP) were studied. A linear regression analysis revealed a significant negative association between CRP and lipid profile namely TC, LDL, TG and ApoA-1. During a median (IQR) follow up = 5.5 (3.7-7.7) years 100 (7%) patients died (all causes) of which 33% (33) deaths were attributed to CVD. Forward stepwise regression analysis demonstrated that a low total cholesterol was independently associated with all cause mortality HR (95%CI) 0.75 (0.61, 0.91) and CVD mortality HR (95%CI) 0.49 (0.29, 0.85). In a small cohort 27 SLE patients and 15 healthy controls. We measured endothelial function using flow mediated dilatation of the brachial artery. At baseline we found a significant increase in TG level [1.36 (0.9, 1.87) mmol/l vs0.88 (0.64, 1) mmol/l P= 0.009] and a significant impaired endothelial function in SLE patients compared to the healthy controls [2.86 (0.6, 5.3) vs 6.81 (3.46,8.57), P= 0.03]. After treatment, there was a trend towards reduced TG level and improved endothelial function. Oxidised-LDL did not change significantly. In conclusion, oxidant stress is increased in SLE patients and relates to some measures of subclinical atherosclerosis. Control of inflammation may not be sufficient to completely control this in routine practice. In early RA, active inflammationmay mask any tendency to hyperlipidemia in this population. Low total cholesterol may be the best biomarker of the overall metabolic and inflammatory status of the patients as well as indicating a group with increased risk of future mortality.

Health policy makers are struggling to manage health care and spending. To identify strategies for improving health quality and reducing health spending, policy makers need to first understand health risks and outcomes. Despite lacking some desirable clinical detail, existing health care databases, such as national health surveys and claims and enrollment data for insured populations, are often rich in information relating patient characteristics to heath risks and outcomes. They typically encompass more inclusive populations than can feasibly be achieved with new data collection and are valuable resources for informing health policy. This dissertation illustrates how the Medicare Current Beneficiary Survey (MCBS) and MassHealth data can be used to develop models that provide useful estimates of risks and health quality measures. It provides insights into: 1) the benefits of a proxy for the Framingham cardiovascular disease (CVD) risk score, that relies only on variables available in the MCBS, to target health interventions to policy-relevant subgroups, such as elderly Medicare beneficiaries, based on their risk of developing CVD, 2) the importance of setting appropriate risk-adjusted quality of care standards for accountable care organizations (ACOs) based on the characteristics of their enrolled members, and 3) the outsized effect of high- frequency hospital users on re-admission measures and possibly other quality measures. This work develops tools that can be used to identify and support care of vulnerable patients to both improve their health outcomes and reduce spending – an important step on the road to health equity.

Thesis (MPH.) -- University of Limpopo, 2019 / The purpose of this study was to profile selected cardiovascular disease risk factors among HIV patients on ART in Bushbuckridge sub-district. Quantitative, crosssectional research was conducted to describe cardiovascular disease risk factors among HIV patients on ART in Bushbuckridge Sub-district. Data collection was done using researcher-administered questionnaires. Adult HIV patient on ART participated in the study (n=328). The study has highlighted cardiovascular disease risk factors and prevalence of cardiovascular disease risk factors among HIV patients on ART. The findings revealed the prevalence of hypertension is 34.6% among HIV patients on ART and men had a higher prevalence compared to women. There is an increase in body mass index and it is seen mostly among women. Alcohol consumption is highest in the young adults (18 to 24 years) both men and women. Health promotion and policymaking interventions need to improve strategies on management and prevention of cardiovascular disease risk factors. Key concepts HIV, ART, cardiovascular disease risk factors, prevalence, body mass index, Bushbuckridge

Parental and offspring life spans are modestly associated and a transmission of disease risk from parents to offspring has been proposed as a possible explanation. Using birth cohort data consisting of 86 168 offspring and their parents, the aim of this explorative study was to quantify and describe the association between parental age-at-death and risk of disease in offspring over a 33-year follow-up period. Hospitalizations due to diseases of the circulatory, musculoskeletal, and digestive systems, as well as mental and behavioural disorders and neoplasms were studied using standard survival analysis methods. Increased parental age-at-death was clearly associated with lower hazard rates for all disease outcomes except for neoplasms. Offspring to short-lived parents had a 59% higher hazard rate (HR: 1.59, 95% CI: 1.52 – 1.67, p<0.00) for hospitalization due to circulatory diseases compared to offspring of long-lived parents. For all disease outcomes except for neoplasms, there was a strong gradient in the offspring’s hazard rates based on parental age-at-death. Hazard rates were only minimally reduced when adjusting for parental SEI and parental household income. The results support a disease-mediated pathway linking parental age-at-death to disease risk in offspring across a wide range of disease outcomes.

The agriculture sectors in Canada are highly vulnerable to a wide range of inter-related weather risks linked to seasonal climate variability (e.g., El Ni ̃no Southern Oscillation(ENSO)), short-term extreme weather events (e.g., heatwaves), and emergent disease(e.g., grape powdery mildew). All of these weather-related risks can cause severe crop losses to agricultural crop yield and crop quality as Canada grows a wide range of farm products, and the changing weather conditions mainly drive farming practices. This dissertation presents three machine learning-based statistical models to assess the weather risks on the Canadian agriculture regions and to provide reliable risk forecasting to improve the decision-making of Canadian agricultural producers in farming practices. The first study presents a multi-scale, cluster-based Principal Component Analysis(PCA) approach to assess the potential seasonal impacts of ENSO to spring wheat and barley on agricultural census regions across the Canada prairies areas. Model prediction skills for annual wheat and barley yield have examined in multi-scale from spatial cluster approaches. The ’best’ spatial models were used to define spatial patterns of ENSO forcing on wheat and barley yields. The model comparison of our spatial model to non-spatial models shows spatial clustering and ENSO forcing have increase model performance of prediction skills in forecasting future cereal crop production. The second study presents a copula-Bayesian network approach to assess the impact of extreme high-temperature events (heatwave events) on the developments of regional crops across the Canada agricultural regions at the eco-district-scale. Relevantweather variables and heatwave variables during heatwave periods have identified and used as input variables for model learning. Both a copula-Bayesian network and Gaussian-based network modeling approach is evaluated and inter-compared. The copula approach based on ’vine copulas’ generated the most accurate predictions of heatwave occurrence as a driver of crop heat stress. The last study presents a stochastic, hybrid-Bayesian machine-learning approach to explore the complex causal relationships between weather, pathogen, and host for grape powdery mildew in an experimental farm in Quebec, Canada. This study explores a high-performance network model for daily disease risk forecast by using estimated development factors of pathogen and host from recorded daily weather variables. A fungicide strategy for disease control has presented by using the model outputs and forecasted future weather variability. The dissertation findings are beneficial to Canada’s agricultural sector. The inter-related weather risks explored by the three separate studies in multi-scales provide a better understanding of the interactions between changing weather conditions, extreme weather, and crop production. The research showcases new insights, methods, and tools for minimizing risk in agricultural decision-making / Graduate / 2021-08-19

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