Faculty of Medicine and Health Sciences

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The vision of the Faculty of Medicine and Health Sciences is to be a dynamic, people-centred and inclusive environment, internationally recognised for its excellence in research, education and clinical training in medicine and health sciences, and for the contribution it makes to improving health and health care in South Africa, the African continent and beyond.

This faculty was known as the Faculty of Health Sciences until 30 April 2012.

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2020-12-11 Global transcriptomic investigation of the human macrophage response towards pathogenic/non-pathogenic mycobacteria
(Stellenbosch : Stellenbosch University, 2019-12) Mishra, Abhilasha Madhvi; Baker, Bienyameen; Leisching, Gina; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Biomedical Sciences: Molecular Biology and Human Genetics
Background:Tuberculosis (TB) is a major cause of infection-related mortalityworldwide. In 2017 an estimated 1.3 million people who were HIV-negative died of TB. An estimated 5-10% of infected individual develop active TB during their lifetime, while the remaining90% (of infected population) successfully control the bacteria. Also, some of the close household contacts of TB patients remain uninfected and healthy. Studying host immune response towards Mycobacterium tuberculosis(M. tb) can unfold the reason behind this enigma. Methods:We conducted a detailed investigation of in vitrohost response from human monocyte derived macrophages(hMDMs)towards different strains of mycobacteria(grown in detergent-freemedia), i.e. pathogenic (M. tbR179) andnon-pathogenic (M. smegmatisand M. bovisBCG). The host response was measured post-infection (at mRNA and protein levels) using AmpliSeq, quantitative real time polymerase chain reaction (qRT-PCR), multiplex ELISA (Luminex), intracellular mycobacterial survivaland cytotoxicity assay. Biological network analysis (ingenuity pathway analysis IPA) was performed to understand the gene regulatory networkinvolved in the pathophysiology associated with the host-immune system.Based on false discovery rate (FDR) and biological functions, we selected an inter-related gene family of interferon induced protein with tetratricopeptides (IFIT1, IFIT2 andIFIT3) from the list of 19 potential differentially expressed genes(DEGs)for knock-up (vector-based over-expression)/down experiments. This gene family is known to form a protein complex during viral infection to act against the antigen. Studyencompassing their role against bacteria is not well established.Therefore, we performed knocking-up of IFITsvia vector-based transfection and knocking-down via small interferingRNA (siRNA) approach to investigate their effect upon mycobacteria inside the host macrophages. Results:AmpliSeqanalysis found 19 DEGs at 12 hours post-infection across all three strains. We observed lower number of mycobacterial CFUs and higher host response (at both RNA and protein level) in hMDMs infected with M. smegmatisas compared to other two strains. Biological network analysis revealed interferon-interleukin associated signalling pathways as most prominent among the 19 differentially expressed genes.We found a differed host response towardsall three strains, which mayattributeto their pathogenicity. Messenger RNA and protein level comparisons at different time points, depicted strong role of interferon and interleukin associated gene network. This network was able to successfully counter M. smegmatisbut succumb to M. bovisBCG andM. tbR179. Most importantly, across all three strains, intra-cellular bacterial growth and survival measured through colony forming units (CFUs)decreased significantly upon knocking up of IFITs(IFIT1, IFIT2 andIFIT3),while we recordedan increase in CFUs upon knocking down ofIFITsin the host macrophages. Using multiplex ELISA, we found higher expression of key pro-inflammatory cytokines (i.e. IDO1, IFN-γ, IL-6, and IL-23) during knock-up (vector-based over-expression)of IFITsresulting in reduction of mycobacteria. Conclusion:Differentially expressed IFITs showed a strong effect against mycobacteria, which can be used as a promising therapeutic targetadjunct to anti-TB therapy. This knowledge will broaden the scope of host drug targets for resistance free bacteriostatic immuno-therapy.
3D measurement of cervical and thoracic postural dynamism in sitting : a pilot study
(Stellenbosch : Stellenbosch University, 2013-12) Fourie, Sarie Marissa; Louw, Quinette; Van Niekerk, Sjan-Mari; Van der Westhuizen, Gareth; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Interdisciplinary Health Sciences. Physiotherapy.
ENGLISH ABSTRACT: The aim of this study was to improve the measurement of postural dynamism in the sitting position using a three-dimensional (3D) motion analysis system. The primary objective was to describe pilot data for postural dynamism of the cervical and thoracic spines while working at a desktop computer. The secondary objective was to refine the process of posture measurement and analysis by decreasing data processing time. Certain factors in 3D motion analysis can lead to an increase in gaps in data collected during trial capture, which in turn will lead to a longer time of data processing. In the first phase of this study, a number of such factors were identified and altered. A series of pilot studies was performed to test the improvement of data processing time when altering these factors. In the first two pilot studies, camera and tripod positionings were explored and refined, workstation layout and anatomical landmark marker placement were investigated, and optimal capture frequency was established. In both these pilot studies, outcomes were established by means of trial and error by experimenting with a variety of different options for the different outcomes. In the third pilot study, computer software which provides computer tasks for the participant during primary trial capture was tested. Two independent computer users performed all the activities as per software, after which they were required to give oral feedback and suggestions on improvement in terms of user friendliness. The objective of the fourth and final pilot study was to include all of the outcomes from the preceeding pilot studies and attempt a trial run of the actual data collection process. A study participant with no affiliation to the research project was used and a complete trial run was performed after which the measurement process was deemed feasible. In the primary study, 18 student volunteers completed a sequence of computer tasks, including keyboard, mouse and reading activities. Prior to data capture, full range of motion of the thoracic and cervical spines were measured in three dimensions for every participant. Data capture took place for the full duration of performance of all computer activities. Outcome parameters for postural dynamism included true range of motion (degrees), proportional range of motion (percentage) and motion frequency (movement per minute) in all three planes of motion of the cervical and thoracic spines. Typing tasks were associated with biggest movement ranges and motion frequencies. Mouse activity was associated with the most stationary posture, exhibiting the least frequent movement as well as the smallest ranges of motion. The results from this study allow us to better understand the dynamic nature of posture, as well as postural dynamism associated with different computer tasks. This study provides a baseline for future research of 3D motion analysis of the sitting posture. It also marks the need for further research regarding ergonomics, use and potential alternatives in the computer workstation and input devices.
The ability of the thromboelastogram (TEG® R-time difference between kaolin and heparinase) as a point of care test to predict residual heparin activity after in vitro protamine titration
(Stellenbosch : Stellenbosch University, 2017-12) Joseph, Lauren Ann; Levin, Andrew I.; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Anaesthesiology and Critical Care.
ENGLISH ABSTRACT: Background: Differentiation between surgical bleeding and coagulopathy is critical as re-exploration is associated with increases in mortality and morbidity. Adequate reversal of heparin with protamine at the end of cardiopulmonary bypass (CPB) is critical to prevent postoperative bleeding. Meticulous dosing of protamine is required as excessive dosages has deleterious side effects on clotting. Traditional methods make use of an activated clotting time (ACT) for evaluation of adequate heparin reversal. However, recent use of other point of care (POC) tests, the thromboelastogram (TEG®) has started challenging the utility and exclusive use of ACT to evaluate effective reversal. Differences between thromboelastographic Rkaolin and R-heparinase times is an indicator of residual heparin. However, the exact relationship between these parameters and the exact amount of residual heparin is unknown. The rationale for this study was to accurately determine the relationship between the magnitude of the R-kaolin and R-heparinase time difference and blood heparin concentrations. Aims: This study was performed to define the in-vitro relationship between the difference between the thromboelastographic R-kaolin and R-heparinase time difference (TEG® Delta-kh R-time) and plasma heparin concentrations. The primary outcome was to determined the relationship between the TEG® Delta-kh R-time difference and heparin concentrations. The secondary outcome was to determine the concentration of heparin at or below which R-kaolin times become measureable. Methods: This was a single centre, prospective, randomized laboratory study. Following institutional ethics approval and informed consent, sixty-two samples were taken during CPB from 20 patients meeting inclusion criteria. Samples were randomized to one of three groups which would dictate the protamine dose. The three groups were based on a protamine to heparin ratio (expressed as milligram protamine per milligram heparin administered to the patient) approximating 0.25, 0.5, and 0.75 mg/mg respectively. Each sample of blood was then administered a dose of protamine. The TEG® analysis entailed measuring the R-kaolin and R-heparinase time and noting the difference. Thereafter, each blood sample was sent for heparin concentration determination using an anti-Xa activity assay. Results: No relationship between the measurable R-kaolin time and heparin concentration could be demonstrated (p=0.80), as well as no relationship between measurable TEG® Delta-kh R- time difference and heparin activity (p=0.42). However, we did identify a high probability to be able to predict a measurable R-kaolin time (negative predictive value 90%, 95% CI 74% to 98%) when heparin concentration is less than 1.24IU/ml. Conclusions: We were unable to predict heparin concentration using TEG® in this study. It is likely that this was related to methodological problems. The protamine dose was a complex calculation and there is uncertainty with regard to the actual amounts used. There were also multiple laboratory technicians, with a possible loss of standardization. However, R-kaolin time will likely be measurable at heparin concentrations below 1.24 IU/ml, and not measurable above that value. This observation is immensely valuable for clinicians and researchers. Future studies should take this into account and attempt to determine the relationship between TEG® Delta-kh R- time differences and heparin activity only when heparin concentration are less than 1.24IU/ml.
Abnormal eating attitudes and weight loss behaviours of girls attending a "traditional" Jewish high school in Johannesburg : an examination of teachers' awareness
(Stellenbosch : University of Stellenbosch, 2011-03) Notelovitz, Talia; Visser, J.; Szabo, C. P.; Fredericks, N.; Harvey, J.; University of Stellenbosch. Faculty of Health Sciences. Dept. of Interdisciplinary Health Sciences. Human Nutrition.
ENGLISH ABSTRACT: Background: Eating disorders are an important cause of morbidity and mortality in adolescent and young adult women. There is some evidence that Eating disorders may be more common in Jewish females than in their non-Jewish counterparts. Individuals with abnormal attitudes as defined by the Eating Attitudes Test (26-Item version) (EAT-26) are at increased risk of developing an eating disorder. School teachers are required to take an active role in the currently favoured ecological approach to the prevention of eating disorders. Objectives: The current study sought to determine the prevalence of abnormal eating attitudes and weight loss behaviours in a Jewish female adolescent sample and to investigate school teachers’ awareness of these factors and their attitudes towards a school programme to address these. Methods: A cross-sectional study of girls in grades 8 to 11 and teachers of both genders was undertaken at a “traditional” Jewish high school in Johannesburg, South Africa. A questionnaire consisting of the EAT-26 and a modified section of the United States Youth Risk Behaviour Survey (YRBS) was completed by pupils. A questionnaire developed by the researcher for the study was completed by teachers. Results: Two hundred and twenty pupils (response rate 84.3%) and 38 teachers (52.1%) participated. Twenty percent of pupils (n=43) had EAT-26 scores greater than or equal to 20 and 30.2% were found to require clinical evaluation for a potential eating disorder Thirty two point seven percent (n=72) of girls considered themselves to be overweight. Sixty four percent (n=139) were trying to lose weight at the time of the study and 19.1% (n=42) had engaged in one or more extreme methods of weight loss (fasting, purging or non-prescribed medication) in the past 12 months. Most teachers (81.6%, n=29) underestimated the proportion of girls requiring clinical evaluation and 71.1% (n=27) underestimated the extent of current weight loss attempts. Almost all (97.3%, n=37) the teachers recognised the need to address disordered eating attitudes and patterns in the school but only 34.2% (n=13) viewed the school as the appropriate place, would be prepared to participate and would give up class time. Conclusions: This is the first study to document the presence of abnormal eating attitudes among Jewish adolescent females in South Africa. The prevalence fell within the upper end of the range of rates reported in studies of adolescent girls in South Africa and abroad. Dieting and attempts at weight loss are common in this population and are also in keeping with the findings from international studies. This is the first study to measure teachers’ awareness of the eating attitudes and weight loss behaviours of girls attending the school at which they teach. The teachers participating in this study were not fully aware of the extent to which eating-related issues affect female pupils. Over and above this, there appears to be a resistance to facilitating and participating in a school programme addressing these issues. A qualitative exploration of this could yield valuable insights.
Abnormalities of bone and mineral metabolism in patients with eating disorders
(Stellenbosch : Stellenbosch University, 2001) Conradie, Maria Martha; Hough, F. S.; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Biomedical Sciences. Division Medical Physiology.
ENGLISH ABSTRACT: Osteopenia is a well documented complication of anorexia nervosa (AN). The pathogenesis of this bone loss is presently poorly defined in the literature. Pathogenetic mechanisms that have been implicated include certain nutritional factors, exercise abuse, hypogonadism, hypercortisolism and/or vitamin 0 deficiency. We studied, 59 Caucasian eating disorder patients aged 15-45yr. The eating disorder was classified by a single, qualified psychiatrist according to OSM IV R criteria as either anorexia nervosa (AN: n =25), bulimia nervosa (BN: n = 17) or eating disorder not otherwise specified (EONOS: n = 17). All patients were subjected to a detailed dietary and general history. We assessed the prevalence and severity (OEXA), the nature (osteocalcin, deoxypyridinoline) and site (vertebral versus hip) of osteopenla in these patients. he role of nutritional factors (energy intake, weight, height, BMI, plasma albumin, lipids), physical activity, hypercortisolemia (plasma and urinary free cortisol), vitamin 0 deficiency (plasma 250HD) and hypogonadism (amenorrhoea, E2, LH, FSH) in the pathogenesis of bone loss were also evaluated. Mild osteopenia (BMO decreased by more than 1SO below age-matched controls) was documented in 46% of the total study population, with more marked osteopenia (Z-Score < -2 SO) present in 15%. Both vertebral and hip osteopenia were documented. In the study population those patients with AN (Lumbar BMO (q/cm") = 0.869 ± 0.121) were most likely to develop osteoporosis, although a significant percentage of patients with BN (Lumbar BMO (q/crn") = 0.975 ± 0.16) and EONOS (Lumbar BMO (g/cm2) = 0.936 ± 0.10) were also osteopenic (29% and 35% respectively). Twenty four percent (24%) of the total patient population had a history of fragility fractures. These fractures were reported more commonly amongst patients with AN and EONOS (28% and29.4%). Fracture prevalence was however similar in patients with normal and low bone mass. Conventional risk factors were similar in patients with normal and low bone mass, except for a significantly longer duration of amenorrhoea (p = 0.009), a lower BMI (p = 0.0001) and greater alcohol consumption (p = 0.05) in the osteopenic patients. Nutritional parameters (S-albumin, protein, Ca, and P04 intakes), physical activity, as well as 25(OH) vitamin D levels were similar in AN and BN subjects, as well as in patients with a low versus normal BMD. Plasma and urine cortisol levels were also similar in these subgroups. With the exception of two patients with borderline osteopenia, significant bone loss was only documented in those patients with a past or current history of amenorrhoea. In the total patient population the duration of amenorrhoea was significantly (p<0.009) longer in patients with osteopenia versus those with a normal bone mass. A significant negative correlation between BMD (Z-Score) and duration of amenorrhoea was also documented in the total patient population (r = -0.4, P = 0.001) as well as in all three eating disorder groups (AN r - -0.4, P = 0.03; BN r = - 0.6, P = 0.008; EDNOS r = -0.6, P = 0.005). In the total patient population, those patients with amenorrhoea, had lower BMD and BMI values and lower estrogen levels compared to those with a normal menstrual cycle. We conclude that osteopenia commonly attends AN, as well as BN and EDNOS. Nutritional (with the exception of alcohol consumption) and mechanical factors as well as hypercortisolemia did not appear to contribute significantly to bone loss in this study population. Hypogonadism appeared to be the main cause of the bone loss observed in these patients.
Absenteeism in district rural hospitals in the Eastern Cape : the experiences of nurses
(Stellenbosch : Stellenbosch University, 2022-12) Jonas, Lindill; Anthonie, Ramona; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Nursing & Midwifery.
ENGLISH SUMMARY: Absenteeism is a global concern that has a negative impact on employees, patients and the organization. Whilst absenteeism is exacerbated by working conditions such as resources (human, equipment), rural communities have a higher prevalence of chronic conditions than their urban counterparts which increases the workload. The aim of the study was to explore the experiences of nurses in district rural hospitals in the Eastern Cape. The objectives of the study were to: - Gain understanding of nurses’ experience of absenteeism at the workplace. - Explore the influence of intrinsic factors on absenteeism as experienced by nurses. - Explore the influence if extrinsic factors on absenteeism as experienced by nurses. A descriptive qualitative design was applied. A sample size of 12 was drawn from a total population of 183 at three participating hospitals, using purposive sampling. A pilot interview was conducted using a semi-structured interview guide based on the study’s objectives. Credibility, confirmability, transferability and dependability was assured by using Lincoln and Cuba’s criteria of trustworthiness. All ethical principles were met. Seven themes emerged from data analysis, i.e., managing human resources, work planning and scheduling, job dissatisfaction and workload, diminished patient care, staff well-being, relationship building amid absenteeism and strategies for managing absenteeism. The findings support Hertzberg’s theory on motivation factors regarding what motivates workers to perform well and not be absent from work. Hygiene factors such as heavy workload, lack of equipment, benefits and support staff, poor co-worker relationships as well as inconsistent implementation of policies all contributed to job dissatisfaction and ultimately absenteeism. As a result, human resource policies and practices should be revised and implemented to provide a more supportive work environment to reduce absenteeism.
Academic factors affecting learning at a nursing college in the Western Cape
(Stellenbosch : University of Stellenbosch, 2011-03) Magerman, Yolande Nerissa; Stellenberg, E. L.; University of Stellenbosch. Faculty of Health Sciences. Dept. of Interdisciplinary Health Sciences. Nursing Science.
ENGLISH ABSTRACT: Nursing education, including the individual nurse educator, has a responsibility to society and to students for providing quality education, for maintaining the highest academic standards, for the proficient use of teaching strategies and for ensuring adequate support to learners. These standards were threatened at a particular college in the Western Cape which instigated this study. This study aimed at investigating the academic factors that influenced learning at a particular nursing college in the Western Cape. The objectives included the following possible factors that may have contributed towards the unsatisfactory, academic performances of students: • Nursing as a career choice; • Selection criteria; • Approaches to learning; • Motivation and learning; • Language barrier to learning; and • Factors affecting the learning environment. A non-experimental, descriptive research design was applied with a quantitative approach. The target population (N = 963) consisted of nursing students following the course leading to registration as a professional nurse, according to the South African Nursing Council’s regulation 425, as promulgated by the Nursing Act 50 of 1978, as amended (Nursing Act 33 of 2005). Probability, stratified sampling was used to select the sample of participants (n = 174). A structured questionnaire, consisting of predominantly closed questions, was used for the collection of data. Ethical approval was obtained from Stellenbosch University to conduct this study. Permission to conduct the research was also obtained beforehand from the management of the nursing college being studied, whilst prior informed consent was obtained from each participant. Reliability and validity of the study were assured by means of a pilot study and through the use of experts in nursing research, methodology and statistics. Data was collected and captured by the researcher personally. The data was analysed with the support of a statistician and was expressed as frequencies and in tables and histograms. Descriptive statistics and post-hoc analyses, including tests for statistical associations, were performed. The outcomes from this study showed that third year students (n = 49/23%) spent the most time studying, whilst first years (n = 74/43%) and second years (n = 40/23%) only spent 2.3 hours studying per day. Academic support classes, when offered, were always attended by (n = 64/37%) and most times by (n = 72/42%). The majority of the participants were able to cope with the workload most of the time (n = 107/61%), whilst (n = 51/30%) and (n = 6/3%) of the participants indicated coping seldom and never, respectively. A significant relationship between the ages of participants and being able to cope with the workload (Spearman p-value = 0.02) existed. Results indicated that (n = 83/48%) of the participants received support with language problems, whilst (n = 75/43%) indicated that they did not receive support with language problems. The Afrikaans speaking participants coped the best with the workload (mean score = 1.72), followed by the English speaking students (mean score = 1.68), and lastly the Isi- Xhosa speaking learners (mean score = 1.65). Recommendations made by participants included the following: • Strict adherence to the selection criteria, which should help decrease the attrition rate. • English as a subject / module during the first year was proposed. • The promotion of the proficiency in English, through interaction between English speaking learners and students with English as second language, should be encouraged. • Regular updates of the contents of the curriculum. • The importance of identifying ‘at risk’ students and pro-actively introducing a mentorship programme. • Information technology needed to be improved in many aspects, such as accessibility of Web based communication. Results from the open ended questions showed that participants regarded the teaching strategies as boring. Large classrooms were also mentioned as a problem. Smaller classes were requested to enable more interaction in the class. In conclusion, this study showed that specific academic factors were influencing learning at the nursing college being investigated in the Western Cape. Therefore, recommendations were made in this study, which, if implemented, should result in an improvement in the overall academic performances of students.
Acceptability and accessibility of pre-exposure prophylaxis modalities for HIV prevention (oral daily PrEP, dapivirine vaginal ring and long-acting cabotegravir injectable) among female sex workers in Salt River, Cape Town : a cross-sectional study
(Stellenbosch : Stellenbosch University, 2022-12) Mbuyamba, Rachel; Cois, Annibale; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Global Health. Health Systems and Public Health.
ENGLISH SUMMARY: Background: Female sex workers (FSWs) are at high risk of contracting HIV and have poor access to health care. Evidence is being collected in real world settings on the acceptability and accessibility of pre-exposure prophylaxis (PrEP) amongst FSWs. We explored oral PrEP accessibility, associated factors and acceptability of alternative PrEP modalities. Methods: This cross-sectional study involved 100 HIV-negative FSWs aged >18 years receiving services at the Wits RHI Sex Worker Clinic in Salt River. We tested the association between oral PrEP uptake status and independent variables using logistic regression models. Poisson regression models were used to identify factors associated with oral PrEP accessibility levels. Linear regression was used to identify factors associated with acceptability of alternative PrEP modalities. Results: FSWs with median age 32.6 years (interquartile range 11.7 years) participated in this study, with 97% indicating that they were at risk for HIV infection. Oral PrEP uptake was 33%. Condom use with the main partner (OR = 0.2, 95% CI: 0.0-0.9, sometimes vs. never) was negatively associated with oral PrEP uptake and no previous experience with long-acting drugs (OR = 5.4, 95% CI: 2.2-13.4) was positively associated with oral PrEP uptake. Accessibility of oral PrEP was lower among FSWs for whom sex work was their secondary source of income compared to those for whom sex work was a primary source of income (aIRR for accessibility score = 0.8, 95% CI: 0.7 – 0.9). Acceptability of alternative PrEP modalities was lower among FSWs with previous treatment for sexually transmitted diseases (differences in acceptability scores -5.1, 95% CI: -14.9– 4.6). Long waiting times (72% of participants), PrEP unavailability (27%), PrEP side effects (38%), limited privacy (31%) and nurse unavailability were the main barriers to PrEP uptake. The perceived risk of HIV infection, and the availability (43%) and cost (71%) of PrEP uptake were PrEP uptake facilitators. Conclusions: Oral PrEP uptake among FSWs is currently low. Limited privacy and side effects were the main barriers to PrEP uptake. FSWs were willing to use the new PrEP modalities when available. This study provides valuable lessons for a successful introduction of new PrEP modalities.
Acceptance of and adherence to full anti-retroviral therapy for prevention of mother to child transmission in HIV infected pregnant women with CD4 count above 350 at Nhlangano Health Centre, Swaziland.
(Stellenbosch : Stellenbosch University, 2018-03) Ndakit, Manighuli Kambasu; Blitz, Julia; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Family and Emergency Medicine. Family Medicine and Primary Care.
ENGLISH SUMMARY : Epidemic of HIV infection is hitting Swaziland where the prevalence is among the highest in the world. Nhlangano Health Centre (NHC) in collaboration with Medecins Sans Frontiers Switzerland (MSF Switzerland) opted to hit early by starting Highly Active Anti-retroviral Therapy (HAART) among HIV infected pregnant women with CD4 count cells above 350. This new intervention raised concerns on acceptability and adherence which needed to be assessed. Study design: This was a descriptive study which explored the acceptance of and adherence of pregnant women to full anti-retroviral therapy at Nhlangano Health Centre in the period from 24th June 2014 to 23rd June 2015. The level of adherence was assessed by announced pill counts on subsequent visits. Then, 6 months after initiation, the viral load and a second CD4 count were determined. Results: 98 participants were recruited and initiated; one later died. 80.6% resided in the rural area. 80.6% attended secondary school. Majority were single (79.6%). Mean age was 25.4 years. 64.3% booked at 2nd trimester. Most were multiparous (75.5%). Mean haemoglobin was 11.1g/dl. After 6 months, mean CD4 count was 709.4 up from 554.4 (initial) and 66 (95.6%) had undetectable viral load risen from 14 (20.2%) at initiation. 69 participants (70.4%) were adherent to treatment; 3 (3.1%) of them failed to suppress completely the viral loads. 13 pregnant women refused HAART; of these 12 were interviewed and one declined. The rate of acceptance was 88.3%. Conclusion: Most of the HIV infected pregnant women who visited the clinic accepted the treatment, their CD4 count increased and had undetectable viral loads after 6 months. Anti-retroviral therapy is effective and can be successfully initiated in pregnant women with CD4 count above 350 but should be monitored closely to avoid loss to follow-up.
Access to primary care for persons with spinal cord injuries in the greater Gaborone, Botswana
(Stellenbosch : Stellenbosch University, 2018-03) Paulus-Mokgachane, Thato Michael Moutie; Visagie, Surona; Mji, Gubela; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Global Health. Centre for Rehabilitation Studies.
ENGLISH SUMMARY : Introduction: People with SCI often have great need for health care services, but they report access challenges. Primary care access to people with SCI has not been explored in Botswana. Aim: This study aimed to identify barriers and facilitators that users with spinal cord injuries experience in accessing primary care services in the greater Gaborone. Methods: A quantitative, cross sectional, observational study was done. Data was collected with a structured questionnaire from 57 participants with traumatic and non-traumatic SCI. Descriptive analysis was done. Results: The male to female ratio was 2.8:1. The mean age of participants was 40 (SD 9.59). Road traffic accidents caused 85% of the injuries. Most participants visited primary care facilities between 2 to 10 times in the six months before the study. Participants were satisfied with the services (63%) and felt that facilities were clean (95%) and well maintained (73.5%). Preferential treatment, respect, short waiting times and convenient hours facilitated an acceptable and adequate service. Availability was hampered by insufficient provider knowledge on SCI as indicated by 71.9% of participants, and shortage of consumables (80.7%). Structural challenges (42.1% could not enter the facility by themselves and 56.5% could not use the bathroom) and lack of height adjustable examining couches (66.7%) impeded accessibility. Cost was incurred when participants (64.9%) utilised private health services where public services failed to address their needs. Conclusion: Primary care services were mostly affordable, acceptable and adequate. Availability and accessibility aspects created barriers.
Accessibility and uptake of reproductive health education during earlier youth according to 18 and 19 year old college students in the Cape Town metropolitan area
(Stellenbosch : University of Stellenbosch, 2010-12) McMillan, Lauren; Marais, F.; University of Stellenbosch. Faculty of Health Sciences. Dept. of Interdisciplinary Health Sciences. Nursing Science.
ENGLISH ABSTRACT: Reproductive health is the right of every person. The new Children’s Act (Act 38 of 2005) gives to children 12 years and older rights to reproductive health, which includes contraceptive access as well as information on sexuality and reproduction. They have the right to HIV/AIDS testing and treatment with only their own consent. The aim of the study was to investigate the personal and contextual factors which influence the accessibility and uptake of reproductive health education during early youth (13 to 18 years). The study also aimed to identify contextually appropriate recommendations toward improved reproductive health provision for these youths. A descriptive, non-experimental, research design was employed with a primarily quantitative approach. A sample of 270 participants, constituting 20% of the study population (N=1373) was randomly selected from Northlink FET Colleges, Cape Town. A self-completion structured questionnaire was used to collect the data. Ethical approval was obtained from the Health Research Ethics Committee of the Faculty of Health Sciences, Stellenbosch University. Permission to conduct the research was obtained from the management of Northlink FET College. A group of 30 participants, who met the inclusion criteria, constituting 11% of the sample, participated in a pilot study. Reliability and validity were assured by means of a pilot study and the use of experts in the field, nursing research and statistics. Data was collected personally by the Principal Investigator. The data analysis was primarily descriptive in nature and presented in frequency tables, proportions and measures of relationships, using where indicated Chi-square (x2) and Mann-Whitney U tests. A thematic approach was used to analyze the qualitative data yielded from the open-ended question. Subsequently, in order to strengthen the investigation, the qualitative data, within the identified themes, was quantified based on a validated analytical approach. The results show that 74.1% (n=195) of participants were sexually experienced by the time of the study. Of the participants who reported having already had sexual intercourse, 60.5% (n=115) indicated having made their sexual début by the age of 16. A third of participants (33.2%,n=77) received their first reproductive health education by age 13. Only half of the participants (50.4%,n=116) indicated that the reproductive health education they received always influenced them to make safer sex choices. Of the participants, 21.9% (n=59) stated that they felt that they were in some way hindered in accessing contraceptives during age 13 to 18 years. The vast majority of the participants (94.4%, n=255) indicated that they would prefer reproductive health education to be provided by a professional healthcare provider at a clinic (61.5%, n=166) or by a nurse at school (33%; n=89). Increased reproductive health education within the schooling systems was requested by 52 (19.3%) participants, with more than 30% (n=84) indicating their home as the preferred source of such education. Several recommendations, grounded in the study findings, were identified, including the provision of reproductive health care and accessibility to contraceptives for youths as young as 12 years within a school setting. This care should be provided by healthcare professionals, such as nurses, on a similar operating basis as that which is provided in primary health clinics. The findings reveal to the pressing need for the development, implementation and evaluation of an alternative model for reproductive health care provision in order to assure the complete deliverance of the rights and care to youths as stipulated in the new Child Act (Act 38 of 2005).
Accessibility of advanced seating services in a Western Cape setting : a qualitative exploration of the experiences of carers of children with cerebral palsy
(Stellenbosch : Stellenbosch University, 2019-12) North, Gwen-Lynn; Visagie, Surona; Geiger, Martha; Stellenbosch University. Faculty of Medicine and Health Sciences. Centre for Rehabilitation Studies.
ENGLISH SUMMARY : Background: It is important for health professionals to understand the experiences of carers of children with cerebral palsy (CP) when accessing health care. Understanding their experiences might help providers to make services more accessible. Aim of the study: To explore the experiences of carers of children with CP (GMFCS IV/V), around the accessibility of advanced seating services at a tertiary healthcare facility in the Western Cape. Methods: This study implemented an exploratory, qualitative research design. Of the study population consisting of 62 carers of children with severe CP, seven carers were purposively sampled and interviewed. Thematic analysis with an inductive reasoning process was used to analyse and generate themes from the semi-structured interviews that were conducted. Findings: Carers experienced a great deal of stress around accessing the tertiary healthcare facility for the seating appointment. Four themes were generated: (1) A strenuous experience, (2) Transport, (3) The child and the buggy, and (4) Facilitators to access. Conclusion: Carers encountered barriers, such as transport, that limited access to the tertiary healthcare facility to attend the advanced seating clinic. Service providers need to take cognisance of the challenges that posture support devices pose to using public transport when prescribing a posture support wheelchair. Service providers should consider decentralizing seating services. There is room for improvement of the current public transport systems to be more inclusive for carers, their children with CP and their posture support wheelchairs by enacting legislation in the Western Cape.
Accessory gene components for an HIV-1 subtype C vaccine : functional analysis of mutated Tat, Rev and Nef antigens
(Stellenbosch : Stellenbosch University, 2002-12) Scriba, Thomas Jens; Van Rensburg, E. Janse; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Medicine.
ENGLISH ABSTRACT: HIV has attained a global distribution and the number of infected people reached an estimated 28.1 million in sub-Saharan Africa at the end of 2001. HIV-1 subtype C is overwhelmingly prevalent in Botswana and South Africa and to date no interventions have been successful enough to curb the rapid spread of the virus. A number of HIV-1 vaccine strategies are being developed, however the breadth and efficacy of such candidate vaccines, many of which are based on the HIV-1 structural genes pol, gag and env, have mostly been found to be inadequate. The HIV-1 accessory genes are attractive components of HIV vaccines due to their role in viral pathogenesis, early expression and the high ratio of conserved CTl epitopes. Yet, because of undesirable properties questions regarding their safety as vaccine components are raised. In this study candidate tat, rev and nefmutants were assessed for efficient expression and inactivation of undesirable functionality. / Plasmid constructs that encode the South African HIV-1 subtype C consensus Tat, Rev and Nef proteins were constructed. The coding sequences of the genes were codon-optimised for optimum protein expression and these synthetic genes were constructed using overlapping 50-mer oligonucleotides. Furthermore, the proteins were mutated at previously described sites by PCR-based site-directed mutagenesis to render them inactive for their respective functions. Corresponding wild-type Tat, Rev and Nef constructs were also made from viral isolates that were least dissimilar to the respective consensus amino acid sequences. tn vitro expression of the different constructs were assessed in 293 cells by Western blotting with polyclonal mouse sera, which were generated by DNA immunisation with one of the Tat, Rev and Nef constructs. The transactivation activity of Tat variants and Rev-mediated nuclear export activity of RRE-containing transcripts were studied in cotransfection experiments using reporter-gene-based assays while Nef functionality was assessed in a cotransfection assay with subsequent flow cytometric analysis of surface CD4 and MHC-I expression on 293 cells. Sequence analysis of the South African HIV-1 subtype C consensus sequences of Tat, Rev and Nef revealed a high degree of similarity with a consensus sequence that was drawn up from a large number of viruses from southern Africa. These consensus sequences were also closer to individual viral isolate sequences than any individual sequences were, indicating that the use of a consensus sequence may serve to reduce genetic diversity between a vaccine and circulating viruses. Expression levels of the sequence-modified tat and nef gene constructs were not significantly higher than the wild-type constructs, however, the codon-optimised rev mutant exhibited markedly higher expression than the wild-type rev construct. Immunoreactivity of the protein with the mouse sera demonstrates expression and immunogenicity of the Tat, Rev and Nef immunogens in mice. In the background of the subtype C Tat, a single C22 mutation was insufficient to inactivate l TRdependent CAT expression in 293T and Hela cells. Yet, this activity was significantly impaired using the single mutation, C3?, or the double mutation, C22C3? Compared to the wild-type Rev, the function of the Rev with a double mutation, M5M10, was completely abrogated. Similarly, while the wild-type Nef and native, codon-optimised consensus Nef proteins mediated CD4 and MHC-I downregulation, CD4 downregulation was completely abrogated in one of the mutants, while both Nef mutants were entirely deficient for MHC-I downregulation. These data demonstrate the high expression levels and impaired functionality of sequence-modified HIV-1 subtype C consensus Tat, Rev and Nef DNA immunogens that may be used as single-standing vaccine components or form part of a multicomponent HIV-1 vaccine.
Accommodating children with mobility impairments in ordinary primary schools : perceptions of school principals in Johannesburg East on barriers and possible solutions
(Stellenbosch : Stellenbosch University, 2021-02) Hunt, Paulani; Luger, Rosemary; Visagie, Surona; Stellenbosch University. Faculty of Medicine and Health Sciences. Centre for Rehabilitation Studies.
ENGLISH SUMMARY: Twenty years ago, the Department of Basic Education in South Africa introduced the Education White Paper 6: Building an inclusive education and training system, to ensure that all children between seven and 15 could access quality basic education. The purpose of this qualitative exploratory study in the Johannesburg East District of Gauteng was to establish the barriers that ordinary primary schools experience to accommodate children with mobility impairments, and what structures and procedures they put in place to bridge those barriers. Data was collected through semi-structured interviews with eight principals and a thematic analysis revealed that barriers included structural challenges like stairs and uneven school grounds, insufficient support from the District, and attitudinal barriers. Some schools devised cost-effective ways to overcome these barriers through collaboration with the community, educators, parents and children, but others were still waiting for external guidance and assistance. To ensure that all children with mobility impairments are reasonably accommodated, schools will need further assistance from the Gauteng Department of Education.
Accommodation of accessibility survey in primary care clinics of a rural Alberta community
(Stellenbosch : Stellenbosch University, 2014-12) Van der Linde, Erich; Pather, Michael; Stellenbosch University. Faculty of Health Sciences. Department of Interdisciplinary Health Sciences.
ABSTRACT Introduction: According to the Society of Rural Physicians of Canada’s National Rural Health Strategy, 21% of Canadian residents are rural but only 9.4% of Canadian physicians live in rural areas.1,2 Aim: To evaluate patient experience and the accommodation of accessibility to four primary care clinics in Brooks, Alberta. Objectives were to: • measure and compare the actual versus expected waiting times in the physician’s office. • assess patient satisfaction with the current organization of access and quality of care. • elicit ideas from patients on how to improve the accommodation of access. • elicit feedback from patients regarding the employment of alternative practitioners in the clinics. Methods: Design: cross-sectional survey. Setting: Four primary care clinics in the city of Brooks. Subjects: The study sample (n=391) included registered patients including emergency walk-in consultations, consultations for office procedures, short visits for prescription refills as well as annual physical examinations. Results: The mean perceived waiting room time was 12.35 minutes versus 5-15 minutes actual waiting room time for 60.5% of the participants. The mean perceived exam room waiting time was 10.58 minutes versus 5-15 minutes actual exam room waiting times for 81.4 % of the participants. Mean perceived time spent with the physician was 11.65 minutes versus 5-15 minutes actual time spent with the physician for 67.1 % of the participants. Patients who felt that they can get a timely appointment were 8.4 times more likely to be happy with the quality of care received. Patients who got prompt return of their calls are 10.4 times more likely to be happy with access to primary care clinics. Patients who felt that the clinic hours of operation were acceptable were 15.6 times more likely to agree that they received adequate health care. Patients who felt that the waiting time for an appointment at the clinic were acceptable to them were 8.1 times happier with the quality of care. Conclusion No major differences exist between perceived and actual waiting times in the physician’s offices. The waiting time for scheduled appointments is generally too long. The most satisfied patient appears to be someone whom waits no longer than 5-15 minutes in the waiting room, then no longer than 5-15 minutes in exam room for a 5 -15 minute consultation. The shorter the waiting times for an appointment and the shorter the different waiting times during a consultation in the clinic the more satisfied the patient.
Accuracy and completeness of notification of tuberculosis in two high incident communities in Cape Town, South Africa
(Stellenbosch : Stellenbosch University, 2011-12) Dunbar, Rory; Barnes, J. M.; Beyers, Nulda; Stellenbosch University. Faculty of Health Sciences. Dept. of Interdisciplinary Health Sciences. Community Health.
ENGLISH ABSTRACT: Introduction: Tuberculosis (TB) treatment registers and laboratory records are essential recording and reporting tools in TB control programmes. Reliable data are essential for any TB control programme but under-registration of TB cases has been well documented internationally, due to under-reporting of patients on treatment or failure to initiate treatment. The accuracy and completeness of routinely collected data are seldom monitored. Aim: This study used record linking to assess the accuracy and completeness of TB treatment register data and the feasibility of estimating the completeness of bacteriological confirmed pulmonary TB registration in two high incident communities in South Africa with capturerecapture methods. Methods: All cases of bacteriologically confirmed TB defined as 2 smear-positive results and/or at least one culture-positive result were included. Record linking was performed between three data sources: (1) TB treatment registers; and (2) all smear and culture results from (a) the nearest central laboratory, and (b) the referral hospital laboratory. To estimate the completeness of TB treatment recording three-source log-linear capture-recapture models were used, with internal validity analysis. Results: The TB treatment registers had 435 TB cases recorded of which 204 (47%) were bacteriologically confirmed cases. An additional 39 cases that were recorded as nonbacteriological cases in the TB treatment register, were reclassified as bacteriologically confirmed. In addition, there were 63 bacteriologically confirmed cases identified from the laboratory databases which were not recorded in the TB treatment register. The final total number of bacteriologically confirmed TB cases across all 3 databases was 306, an increase of 50% over what had initially been recorded in the TB treatment register. The log-linear capture-recapture model estimated the number of bacteriologically confirmed TB cases not found in any of the data sources at 20, resulting in a total number of bacteriologically confirmed TB cases of 326 (95% CI 314-355). The completeness of registration of bacteriologically confirmed pulmonary TB cases was 79% after record linking and 75% after the capture-recapture estimate. Conclusions: The results presented in this thesis highlighted the concern regarding the accuracy and completeness of routinely collected TB recording and reporting data. A high percentage of bacteriologically confirmed cases from both laboratories were not recorded in the TB treatment registers. Capture-recapture can be useful, but not essential, for evaluation of TB control programmes, also in resource-limited settings, but methodology and results should be carefully assessed. The present study estimated the extent of the problem of underreporting of TB in South Africa and identified challenges in the process. Interventions to reduce underreporting of TB are urgently needed.
Accuracy and impact of the MTBDRplus v2 and MTBDRsl v2 line probe assays for the detection of first-line and second-line drug resistant tuberculosis
(2023-02) Pillay, Samantha; Theron, Grant; de Vos, Margaretha; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Biomedical Sciences. Molecular Biology and Human Genetics.
ENGLISH ABSTRACT: Combating drug-resistant tuberculosis (DR-TB) remains a challenge globally. Treatment success rates are often derailed by under-diagnosis and under-reporting of disease. Patients remain contagious for prolonged periods prior to initiation of appropriate treatment which is further exacerbated by the amplification of drug resistance and poor treatment outcomes. Using current and new diagnostic tools effectively is key to rapid diagnosis of tuberculosis and early detection of drug resistance. Firstly, (chapter 2) line probe assays (LPAs) frequent inability to generate a resistance call in paucibacillary specimens is problematic. We showed that while MTBDRplus and MTBDRsl tests work well on smear-negative specimens for detecting drug resistance, failure rates remained high. We demonstrated with the use of routine key programmatic data how time-to-reporting of results improved with the use of molecular assays and provided evidence on how standard-of-care can be improved in a programmatic context. Secondly, (chapter 3) LPA testing on smear-negative specimens is not always performed causing diagnostic delays and hindering their role as a direct front-line diagnostic tests. Thus, by using Xpertgenerated data we determined the ratio of actionable-to-non-actionable results and the number of missed resistant cases at varying thresholds. We demonstrated that Xpert semiquantitation category is superior to informing reflex LPA testing than smear status. In short, this method provides a framework by which laboratories that currently do not test smear-negative specimens to expand testing. Thirdly (chapter 4) current pathways using Xpert MTB/RIF or Xpert Ultra as frontline tests for diagnosing TB and rifampicin resistance lack further treatment guidance. We did a systematic review and assessed the performance of Xpert MTB/XDR for the detection of pulmonary tuberculosis and resistance to isoniazid, fluoroquinolones, ethionamide, and amikacin. Participants consisted of 1228 for pulmonary tuberculosis detection and 1141 for drug resistance. We found Xpert MTB/XDR is unlikely to test positive as a follow-up test for the detection of Mycobacterium tuberculosis in samples that test Xpert Ultra
The accuracy of non-invasive blood pressure monitoring when compared to intra-arterial blood pressure monitoring in patients with severe pre-eclampsia during an acute hypertensive crisis
(Stellenbosch : University of Stellenbosch, 2010-12) Dalla, Sangita; Langenegger, Eduard; Petro, Gregory; University of Stellenbosch. Faculty of Health Sciences. Dept. of Obstetrics and Gynaecology.
ENGLISH ABSTRACT: OBJECTIVE: The aim of this study was to compare the accuracy of non-invasive blood pressure measurements, using automated and manual devices, against invasive intra-arterial blood pressure measurements in patients with pre-eclampsia, during a hypertensive blood pressure peak. STUDY DESIGN: In this prospective study, women admitted to the Obstetrics Critical Care Unit, with confirmed pre-eclampsia and acute severe hypertension, who had an intra-arterial line in situ, were asked to participate. During an intra-arterial blood pressure peak, both an automated oscillometric and a blinded manual aneroid sphygmomanometric blood pressure was recorded. These two methods of blood pressure measurements were compared to intra-arterial blood pressure measurements. The accuracy of a mean arterial pressure (MAP) ≥ 125mmHg in detecting a systolic blood pressure (SBP) ≥ 160mmHg, using all three methods, was also determined. RESULTS: There was poor correlation between intra-arterial SBP and automated and manual SBP (r = 0.34, p < 0.01; r = 0.41, p < 0.01 respectively). The mean differences between automated and manual SBP compared to the intra-arterial SBP was 24 ± 17mmHg (p < 0.01) and 20 ± 15 mmHg (p < 0.01) respectively. There was better correlation between intra-arterial diastolic blood pressure (DBP) and automated and manual DBP (r = 0.61, p < 0.01; r = 0.59, p < 0.01 respectively). The mean differences of the automated and manual DBP was not statistically significant when compared to the intra-arterial DBP. There was poor correlation between the intra-arterial MAP and the automated MAP (r = 0.44, p < 0.01) and good correlation with the manual MAP (r = 0.56, p < 0.01). The mean differences of the automated and manual MAP were statistically significant (5 ± 13mmHg, p < 0.01; 8 ± 11mmHg, p < 0.01 respectively). The sensitivity of automated and manual methods in detecting a SBP ≥ 160mmHg was 23.4% and 37.5% respectively. A MAP ≥ 125mmHg in detecting a SBP ≥ 160mmHg, when using intra-arterial, automated and manual methods of blood pressure measurements showed low sensitivity (35.9%, 21.9% and 17.2% respectively). CONCLUSION: This study demonstrated that both the automated and manual methods of blood pressure measurements were not an accurate measure of the true systolic intra-arterial blood pressure, when managing pre-eclamptic patients with acute severe hypertension. In such situations, intra-arterial blood pressure monitoring should be used when possible. When this is not possible, manual aneroid sphygmomanometry is recommended. Underestimating blood pressure, particularly SBP, may lead to severe maternal morbidity and mortality.
Accuracy of risk prediction tools for acute coronary syndrome : a systematic review
(Stellenbosch : Stellenbosch University, 2015-04) Van Zyl, Johet Engela; Khondowe, Oswell; Stellenbosch University. Faculty of Health Sciences. Interdisciplinary Health Sciences. Nursing.
ENGLISH ABSTRACT: Background: Coronary artery disease is a form of cardiovascular disease (CVD) which manifests itself in three ways: angina pectoris, acute coronary syndrome and cardiac death. Thirty-three people die daily of a myocardial infarction (cardiac death) and 7.5 million deaths annually are caused by CVD (51% from strokes and 45% from coronary artery disease) worldwide. Globally, the CVD death rate is a mere 4% compared to South Africa which has a 42% death rate. It is predicted that by the year 2030 there will be 25 million deaths annually from CVD, mainly in the form of strokes and heart disease. The WHO compared the death rates of high-income countries to those of low- and middle-income countries, like South Africa, and the results show that CVD deaths are declining in high-income countries but rapidly increasing in low- and middle-income countries. Although there are several risk prediction tools in use worldwide, to predict ischemic risk, South Africa does not use any of these tools. Current practice in South Africa to diagnose acute coronary syndrome is the use of a physical examination, ECG changes and positive serum cardiac maker levels. Internationally the same practice is used to diagnose acute coronary syndrome but risk assessment tools are used additionally to this practise because of limitations of the ECG and serum cardiac markers when it comes to NSTE-ACS. Objective: The aim of this study was to systematically appraise evidence on the accuracy of acute coronary syndrome risk prediction tools in adults. Methods: An extensive literature search of studies published in English was undertaken. Electronic databases searched were Cochrane Library, MEDLINE, Embase and CINAHL. Other sources were also searched, and cross-sectional studies, cohort studies and randomised controlled trials were reviewed. All articles were screened for methodological quality by two reviewers independently with the QUADAS-2 tool which is a standardised instrument. Data was extracted using an adapted Cochrane data extraction tool. Data was entered in Review Manager 5.2 software for analysis. Sensitivity and specificity was calculated for each risk score and an SROC curve was created. This curve was used to evaluate and compare the prediction accuracy of each test. Results: A total of five studies met the inclusion criteria of this review. Two HEART studies and three GRACE studies were included. In all, 9 092 patients participated in the selected studies. Estimates of sensitivity for the HEART risks score (two studies, 3268 participants) were 0,51 (95% CI 0,46 to 0,56) and 0,68 (95% CI 0,60 to 0,75); specificity for the HEART risks score was 0,90 (95% CI 0,88 to 0,91) and 0,92 (95% CI 0,90 to 0,94). Estimates of sensitivity for the GRACE risk score (three studies, 5824 participants) were 0,03 (95% CI0,01 to 0,05); 0,20 (95% CI 0,14 to 0,29) and 0,79 (95% CI 0,58 to 0,93). The specificity was 1,00 (95% CI 0,99 to 1,00); 0,97 (95% CI 0,95 to 0,98) and 0,78 (95% CI 0,73 to 0,82). On the SROC curve analysis, there was a trend for the GRACE risk score to perform better than the HEART risk score in predicting acute coronary syndrome in adults. Conclusion: Both risk scores showed that they had value in accurately predicting the presence of acute coronary syndrome in adults. The GRACE showed a positive trend towards better prediction ability than the HEART risk score.
Accuracy Optimization of anti-TB Drug Assays using Protein Evaluation in Calibration Curves during Pharmacokinetics Quality Assurance
(Stellenbosch : Stellenbosch University, 2021-12) Vallie, Sarfaraaz; Stander, Marietjie; Reuter, Helmuth; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. Medicine: Clinical Pharmacology.
ENGLISH ABSTRACT: Quality assurance of drug assaying is an important aspect in clinical testing. Accuracy is important to ensure correct bio-analytical results by constructing calibration curves that took blood matrix interferences into consideration. I have adhered to the United States of America Food and Drug Administration (FDA) call for improved accuracy in bio-equivalence, bio-availability and administering of narrow therapeutic indexed drugs. Significant different plasma levels were observed in clinical trials for the occasional hyperproteinemia (an increase in protein concentration in the bloodstream) and hypoproteinemia (lower-than normal levels of protein in the blood) patients this includes disease-related hyperalbuminemia (an increased concentration of albumin in the blood) and hypoalbuminemia (a deficit of albumin in the blood) patients. This research supported a modeled approach for accuracy improvements by including the patients‘ plasma protein levels using a combined calibration curve (protein evaluation calibrations curves – PROTECC-PKTM). Levels of albumin were classified as marked hypoalbuminemia (<2.5 g/dL), mild hypoalbuminemia (2.5-3.5 g/dL), normal albumin (3.5-4.5 g/dL), and hyperalbuminemia (>4.5 g/dL). This research was specifically important for drugs with a narrow therapeutic index. The rifampicin method was developed, validated and the concentration calibration curve of rifampicin with and without plasma was assessed. The limit of detection for rifampicin with and without plasma was 0.189 μg/ml ± 0.082 and 0.080 μg/ml ± 0.053 μg/ml respectively (LOD ± mean standard diviation). The limit of quantification of rifampicin with and without plasma was 0.573 μg/ml ± 0.082μg/ml and 0.243 μg/ml ± 0.053μg/ml respectively (LOQ ± mean standard diviation). The r2 for rifampicin was 0.9971 without plasma and 0.9852 with plasma present. A novel analytical method for determination of the % protein content present in blood plasma was performed using the Karl Fischer Titration process. Results indicated deviation in % protein of blood plasma for patients compared to literature values of about 8 %. Using the data obtained, the PROTECC-PKTM curves indicated that the relative accuracy differed by a minimum of 0.1% for low binding affinity drugs and a maximum of more than 20% for drugs with moderate binding affinities. The relative accuracy of the anti TB drugs was supported by computational modelling and thermodynamic analytical methods for each drug during multiple drug co-administration regimens. This study focused on the drug binding affinity that affects the extrapolation of the patient‘s sample drug concentration from the slope of LCMS calibration curve. The binding constants calculated from fluorescence spectroscopy data were as follows: rifampicin 5.379 x 102 M-1 (moderate affinity), isoniazid 9.285 M-1 (low affinity), 25-desacetyl rifampicin 3.156 M-1 (low affinity), ethambutol 3.443 M-1 (low affinity) and pyrazinamide 3.076 X 102 M-1 (moderate affinity). These drugs Gibbs free energies for these drugs indicated spontaneous binding reactions. Rifampicin, a non-polar weak acid with a higher affinity, showed the most stable complex formation with human serum albumin (HSA) compared to soluble isoniazid. This is because isoniazid in its ionized form can be easily excreted in the urine resulting in low levels of detection. This will affect the bioavailability and accuracy of the assay levels for patients experiencing hyper and hypoalbuminemia with related competition and induction processes of the enzymes. These complications are apparent where a larger number of patients are involved in clinical trials, bioequivalence and bioavailability studies with varying protein levels that may be more crucial for drugs with a narrow therapeutic index.

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