Electronic Theses and Dissertations (Masters)

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An evaluation of the effects of metal complexes on lung cancer cell lines
(University of the Witwatersrand, Johannesburg, 2024) Mangena, Zanele; Harmse, Leonie
Lung cancer remains a predominant global health concern, accounting for approximately 18% of cancer-related deaths. In South Africa, it imposes a significant burden due to high rates of late-stage diagnoses, resulting in compromised survival outcomes. Despite available targeted therapies, treatment efficacy is hindered by drug resistance and severe side effects, highlighting the need for alternative agents. This study aimed to investigate a series of complexes in an in vitro setting to assess their potential as alternative agents for lung cancer therapy. This study evaluated 20 compounds, encompassing novel epidermal growth factor receptor kinase inhibitors, AD and OM copper complexes, and copper imidazo[1,2-a]pyridines in vitro. Their cytotoxicity against A549 lung cancer cells was determined by the MTT assay, and the most potent compounds were chosen for further investigation. The mode of cell death for these compounds was assessed through cell morphology, Annexin-V, caspase-3/7, mitochondrial membrane potential, and caspase-8 assays. The capacity of the active compounds to induce reactive oxygen species was measured through the CellROX™ Deep Red assay kit. Immunohistochemistry techniques were employed to analyze the expression and distribution of p21 and p53. Furthermore, changes in the expression levels of apoptosis-related proteins post-treatment with the most effective compound were assessed using the Proteome Profiler Human Apoptosis Array kit. Four copper-imidazo[1,2-a]pyridines, namely JD35, JD46, JD47, and JD88, were the most active, with IC50 values in A549 cells between 1.67 μM and 3.37 μM. These compounds induced apoptotic cell death, characterized by chromatin condensation, fragmented nuclei, Annexin-V binding, and activation of caspase-3/7. They also caused a decline in mitochondrial membrane potential, indicating activation of the intrinsic apoptotic pathway, while also inducing late caspase-8 activation. Furthermore, these compounds enhanced reactive oxygen species and upregulated nuclear p21 and p53 expression, suggesting DNA damage leading to apoptosis initiation. Analysis of apoptotic proteome array data showed that JD88 treatment significantly upregulated the wild-type tumour suppressor protein, p53 in A549 cells while significantly downregulating anti-apoptotic proteins such as Bcl-2, Bcl-xL, XIAP, cIAP-2, survivin, and heat shock proteins (HSP27, HSP60, and HSP70). These findings suggest a reduced threshold for apoptosis and a potential promotion of apoptosis, possibly through p53 activation. Copper-imidazo[1,2-a]pyridines have demonstrated effectiveness in inducing apoptotic cell death in A549 cells, impacting both intrinsic and extrinsic apoptotic pathways and influencing critical proteins for cellular survival and apoptosis. This study contributes to a better comprehension of apoptotic mechanisms in A549 cells, stimulating inquiries into the activation of extrinsic apoptotic pathways especially by copper complexes. These findings support further pre-clinical evaluations of copper-imidazo[1,2-a]pyridines, including efficacy assessments in lung cancer animal models, toxicity studies, and determination of pharmacokinetic properties
The wound healing effect of exosomes derived from Lobostemon fruticosus
(University of the Witwatersrand, Johannesburg, 2024) Rajcoomar, Yashmika; Somandi, Khonzisizwe
Exosomes are increasingly being researched and recognized as a novel mode of intercellular communication which can potentially play a significant role in many cellular processes, including immune responses, signal transductions and antigen presentation. Exosomes are membrane bound nanovesicles produced by both mammalian and plant cells. Developing research is mainly focused on their ability to act as a drug delivery vehicle. Other research interests around exosomes are their therapeutic effects for many common diseases including cancer and chronic inflammation. Plant-derived exosomes have emerged as potential candidates for many clinical and therapeutic applications. The aim of this project was to isolate exosomes derived from Lobostemon fruticosus leaves and to investigate the wound healing potential from this plant species. The plant-derived exosomes were isolated by ultracentrifugation and were characterised by means of scanning electron microscopy (SEM), ZetaSizer, Energy-dispersive Xray spectroscopy and the Pierce™ BCA Protein Assay Kit. The wound healing potential was assessed by In vitro scratch assay using human keratinocytes (HaCaT). The exosomes displayed a round, spherical shape and had diameters ranging from 41 to 67 nm – falling within range of nano-sized exosomes. The exosomes had a mean particle size of 166.2 d.nm. Chemical analysis of the samples using energy dispersive spectroscopy revealed the presence of carbon, oxygen, potassium, chloride, gold, palladium and sodium. The protein quantification results revealed the exosomes were rich in proteins. The cell viability results, using various concentrations of Lobostemon fruticosus exosomes, revealed non-cytotoxicity on HaCaT cells. The In vitro scratch assay demonstrated that the exosomes enhanced the migration ability of HaCaT cells in a time dependent manner. The findings suggest and reveal that exosomes derived from Lobostemon fruticosus could accelerate the healing process and can be employed as a future drug delivery platform. Further research is required to establish the exact mechanism of action of the healing potential of this plant specie's constituents. Overall results suggest that exosomes derived from Lobostemon fruticosus are promising as a potential agent for skin regeneration
A Survey of the Delivery of Clinical Services in Independent Community Pharmacies in South Africa
(University of the Witwatersrand, Johannesburg, 2024) Ismail, Tahir; Khan, Razeeya
Introduction The community pharmacists' role has evolved from traditional medicine dispensing to patient- centred service provision. Community pharmacy clinical service provision is an integral component of public health intervention and contributes to universal health coverage. The extent of clinical services offered in community pharmacies in South Africa has yet to be studied. Assessing the extent of clinical service provision in community pharmacies provides insight into the willingness of South African pharmacists to deliver these services. Aim This study aimed to identify the clinical services offered in independent community pharmacies in South Africa and the extent to which these services are available. In addition, the willingness to provide clinical services and the barriers to service provision were also assessed. Methodology A quantitative, cross-sectional exploratory research design was used. Responsible pharmacists of the Independent Community Pharmacy Association member pharmacies were invited to participate in an anonymous electronic REDCap© survey from September 2022 to March 2023. Data was exported to Microsoft Excel® and analysed using descriptive statistics. Results Of the 156 responses received, most were located in urban areas (70%) and based in Gauteng (34.8%). The most frequently delivered clinical services were diabetes screening (88.9%), blood pressure measurement (80.8%) and Influenza vaccination (78.9%). Clinical services were primarily delivered by a pharmacist (39.5%), with most pharmacists (94.7%) willing to implement additional clinical services. However, lack of time and remunerations for services (57.1%) were identified as barriers to implementation. Most pharmacists also expressed an interest in additional training to improve clinical skills. Conclusion This study revealed the extent of clinical service delivery in independent community pharmacies in South Africa. Although community pharmacists are willing to provide clinical services, significant barriers limit these interventions. This study also informs service providers of training programmes that need to be developed to meet the specific needs of independent community pharmacists. Further research must address how the barriers identified may be mitigated to facilitate clinical service implementation in community pharmacies
Brain concentrations and the neurochemical effects of passively administered fluoxetine in Flinders sensitive line rat offspring
(University of the Witwatersrand, Johannesburg, 2023) Steyn, Stephanus Frederik
Background: Globally, 36 % of women who have recently given birth, experience symptoms of depression and anxiety. Effective antidepressant treatments are limited, with fluoxetine being a popular treatment option. Fluoxetine is expressed in the breast milk, yet it is unclear to what extent fluoxetine, or its active metabolite, norfluoxetine, reaches the brain of the developing child and what the effects of such exposure on the related neurobiological processes would be. Due to ethical considerations and practical restrictions, clinical investigations into the neurodevelopmental effects of passively administered antidepressants (via the breast milk) are problematic. Therefore, pre-clinical investigations into this topic are not only important but clinically relevant. Aims & objectives: We aimed to quantify the concentration of passively administered, i.e., via the breast milk during nursing, fluoxetine, and its active metabolite, norfluoxetine in the whole brains of exposed Flinders sensitive line (FSL) rats (an established rodent model of depression). We further aimed to establish if said exposure would associate with changes in whole-brain serotonergic function and redox status. Methods: Adult FSL dams received fluoxetine (10 mg/kg/day), or placebo for fourteen days, beginning on postpartum day 04. Offspring (n = 16 per exposure group; 1:1 male: female) were passively exposed to fluoxetine until postnatal day 18 and euthanized on postnatal day 22. Whole brain fluoxetine, norfluoxetine, serotonin, 5-hydroxyindoleacetic acid (5-HIAA), and reduced and oxidized glutathione (GSH and GSSG) concentrations were measured via liquid chromatography/mass spectrometry (LC-MS). Results: Fluoxetine, was undetectable in the brain of FSL offspring, while norfluoxetine concentrations, averaged 41.28 ± 6.47 ng/g. Neither serotonin, nor its metabolite (5-HIAA), was affected by passively administered fluoxetine in the juvenile brain. In terms of redox status, pups exposed to fluoxetine presented with a compromised antioxidant defence, as evinced by a lower GSH/GSSG ratio. Discussion and conclusion: Although fluoxetine and norfluoxetine concentrations have been measured in breast milk and infant plasma, to the best of our knowledge, it has not been quantified in the juvenile brain until now. Our results are in line with clinical findings, suggesting the infant norfluoxetine/fluoxetine ratio to be elevated, probably because of the prolonged half-life of norfluoxetine. Although only norfluoxetine was detected, this did not influence the central serotonin concentrations of offspring. However, it associated with increased oxidative stress, of which the pathophysiological significance remains to be established. Taken together, our findings confirm that passively administered fluoxetine does reach the infant brain in the form of norfluoxetine and may manipulate processes of oxidative stress regulation. Further studies into the long-term bio-behavioural effects are however needed to effectively inform breast feeding mothers on the safety of antidepressant-use during the postpartum period
Essential oil compounds in combination with conventional antibiotics for dermatology
(University of the Witwatersrand, Johannesburg, 2024) Simbu, Shivar Bram; Van Vuuren, Sandy
Skin and soft tissue infections represent a heterogeneous array of clinical entities with varying severity, causative pathogens, and rates of progression. The slow development and overuse of antimicrobial agents have perpetuated the spread and severity of antimicrobial resistance. Natural products such as essential oils and their compounds are often investigated for their pharmacological properties, with particular interest in their antimicrobial properties. This study aimed to investigate the effects of combining six essential oil compounds (α-pinene, γ-terpinene, ±linalool, eugenol, carvacrol, and cinnamaldehyde) with eight conventional antimicrobials (amoxicillin, ciprofloxacin, erythromycin, gentamicin, meropenem, tetracycline, miconazole, and nystatin) against six commonly encountered skin pathogens (Staphylococcus aureus ATCC 25923, Staphylococcus epidermidis ATCC 12228, Pseudomonas aeruginosa ATCC 27853, Acinetobacter baumannii ATCC 19606, Cutibacterium acnes ATCC 11827, and Candida albicans ATCC 10231) to elucidate the interactive profiles, toxicity, and anti-inflammatory properties. The antimicrobial analysis involved determining the minimum inhibitory concentrations (MIC) of the conventional antimicrobials and essential oil compounds, singularly and in combination, using the broth microdilution assay. The sum of the fractional inhibitory concentrations (ΣFICs) was calculated to investigate the interactive profile of the combinations. Synergistic interactions were further analysed at varying ratios and depicted on isobolograms. Eight synergistic interactions were identified, with seven against Gram-positive bacteria (ΣFIC 0.07– 0.42) and one against P. aeruginosa (ΣFIC 0.32). In addition, it was demonstrated that when in combination, the selected combinations resulted in reduced toxicity (Brine-shrimp lethality assay). The combination of amoxicillin and eugenol demonstrated the lowest toxicity (LC50 = 1081 μg/mL) and the highest selectivity index (14.41) when in a (70:30) ratio with the antibiotic in the higher ratio. Based on the synergistic results from the antimicrobial analysis, a selection of essential oil compounds with conventional antimicrobials were assessed for cytotoxicity and anti- inflammatory properties. The cytotoxicity properties were determined using the MTT assay on HaCAT keratinocytes. The anti-inflammatory properties were determined using lipopolysaccharide (LPS) activated RAW 264.7 macrophages, and the reduction in nitrate (NO) production was measured. Cinnamaldehyde demonstrated the highest cytotoxicity (IC50 = 28.63 μg/mL, p < 0.05) and the greatest reduction (77.44%) in nitrite production, which was also concentration dependent. The combination of ciprofloxacin and cinnamaldehyde demonstrated the lowest cytotoxicity (88.42% ± 3.72 cell viability; combination index of 0.12) and the highest reduction in nitrite production (77.42%; ΣFa = 0.44). Further investigations on the interactive properties of ibuprofen were undertaken. The antimicrobial, cytotoxicity, and anti-inflammatory properties of ibuprofen were analysed singularly and in combination with all essential oil compounds and conventional antimicrobials against reference and clinical skin pathogens. For the MIC results, four synergistic interactions were identified between ibuprofen and conventional antimicrobials (ΣFIC 0.33 - 0.50). For the cytotoxicity (MTT assay), none of the combinations demonstrated a cytotoxic effect (cell viability of 93.6-100%) and significant reduction on nitric oxide production. Additionally, higher order combinations involving the synergistic combinations were investigated with the inclusion of the essential oil compounds. Three synergistic interactions were identified (One against C. acnes and two against A. baumannii). The triple combinations were slightly cytotoxic (cell viability of 77.59 - 90.44%; combination index of 0.95 -1.10) on the HaCAT cell line and did not reduce nitric oxide production. Based on the overall results from this study, combinations of essential oil compounds and some conventional antimicrobials demonstrate promising therapeutic approaches to attenuate antimicrobial resistance. These results demonstrated that combinations that comprise cinnamaldehyde have noteworthy antimicrobial and anti-inflammatory properties which may warrant further investigation. Combining ibuprofen with conventional antimicrobials and essential oil compounds may also offer potential advantages in managing resistant infections through direct and indirect antimicrobial mechanisms.
A retrospective review on the utilisation of meropenem in a tertiary hospital setting
(University of the Witwatersrand, Johannesburg, 2024) Mohun, Shameeda
Introduction: The discovery of antibiotics is widely regarded as a groundbreaking accomplishment in the medical industry, as it has facilitated the elimination of countless diseases. Nonetheless, the overuse and reckless consumption of these medicines have led to a global upsurge in antibiotic resistance, particularly in broad-spectrum antibiotics such as meropenem, which are often prescribed for severe infections. Aim: The aim was, therefore, to assess the utilisation trends of meropenem in treating patients at a tertiary hospital located in the North-West Province of South Africa. Methodology: This study involved a retrospective review of hospital records at a 396-bed tertiary hospital in the public sector of South Africa, for patients who were prescribed meropenem between January and December 2021. A total of 218 patient files were included in the analysis after removing the duplicates and incomplete files. Variables investigated were patient demographics, prescribing criteria, diagnosis, treatment indication, microorganisms, and sensitivity cultures, as well as the appropriateness of prescribing. Descriptive statistics were employed to analyse the data. Results: Meropenem was primarily used empirically in adult patients (65.1%), while clinicians treating paediatric patients generally reserved its use for definitive cases (55.1%). Recording of the source of infection was poor with 72.1% of adults and 96.6% of paediatrics lacking such documentation. Although all prescriptions analysed were deemed valid, only a small percentage of treatments were considered appropriate (3.1% in adults). The study also revealed that clinicians frequently ordered microbiological cultures and blood sensitivity tests prior to administering antibiotics, at rates of 50.4% in adults and 71.9% in paediatrics. Notably, the most cultured bacteria were Klebsiella pneumoniae (25.2%) in paediatric patients and Acinetobacter species (25.0%) in adults. Conclusion: The study's results reveal a clear contrast between suggested protocols and clinical practices in the real world, stressing the pressing need for effective antimicrobial strategies to counter the growing threat of meropenem resistance. Several areas of concern were identified, including non-adherence to guidelines, insufficient step-down therapy, and incomplete documentation. Despite being a broad-spectrum antibiotic intended for definitive diagnoses, meropenem is often prescribed empirically, further highlighting the need for continuous medical education, practical therapeutic committees, and frequent drug utilisation evaluations to tackle this issue
The development of a questionnaire to assess training and match demand in adolescent cricketers
(University of the Witwatersrand, Johannesburg, 2024) Grobler, Nico; Olivier, Benita
Background: Recording training and match demand in adolescent sports is essential in preventing overtraining and injuries while ensuring optimal performance and well-being. The study aimed to develop a valid and reliable questionnaire that would measure the training and match the demands of adolescent cricketers. Methods: In Study 1, the content validity of the training and match demand questionnaire was measured using the content validity index, while the reliability was measured using Kendall’s coefficient of concordance (Kendall’ W). In Study 2, a pilot study was performed using the questionnaire developed in Study 1. Daily training and match demand for all activities done in cricket (i.e., bowling, batting, fielding, strength and conditioning) and any other sport or activities were recorded in 17 adolescent cricketers. Acute:Chronic workload ratios (ACWR) were determined for all activities. Results: The developed questionnaire was deemed valid (I-CVI score of 0.83) and reliable (Kendall’s W score of 0.63). Over the 7-week period, some spikes in the acute training and match demand were observed. However, the overall ACWR was within the norms (0.8-1.3). Bowling reported an average ACWR of 0.91; other sports reported the highest average of 1.08, while the average for all activities combined was 0.92. Conclusion: The questionnaire measured the training and match demand of the cricketer over time and can be used as a valuable tool in future research and practice in adolescent cricket
The Effectiveness of a Multidisciplinary, Protocol-based Approach to Patients of Different Age Groups with Lower Back Pain in Bloemfontein, Gqeberha, Polokwane, and Johannesburg
(University of the Witwatersrand, Johannesburg, 2024) Bennett, Matthew Terence; Neophytou, Natalia
Introduction: Lower back pain is a chronic worldwide condition experienced by many individuals. In Africa specifically, it has been reported that the average lifetime prevalence of lower back pain is 36% within adolescence, and 62% within adults. Although exercise interventions exist there are many gaps in terms of efficacy across age groups; a lack of multidisciplinary approach; as well as, a lack of a reproducible standardised protocol. Furthermore, there is a lack of interventions focusing on pain scale improvements and ROM simultaneously. In the early 90’s, a Documentation Based Care (DBC) multidisciplinary protocol was developed in Finland which aimed to bridge this gap by reducing low back pain, Subsequently it was adapted, and implemented in South Africa, however no information exists as to whether it has been effective in the South African context in terms of improving back pain, as well as improving ROM in individuals. Objectives: To determine whether the current South African adaptation of the Finnish DBC lower back protocol is effective in reducing pain levels and improving range of motion over multiple age groups. Methods: A retrospective analysis of 1499 data sets, of individuals who participated in a standardised 6-week lower back intervention, using the adapted version of the Finnish DBC lower back programme was conducted. Data was extracted from a collated database from 5 Biokinetics practices using the adapted DBC protocol. Data included: age, pre-post intervention visual analogue scale (VAS) pain scale data and lumbar thoracic ROM including flexion, extension, lateral flexion and rotation. Descriptive statistics were used for the demographic data, student T- tests were used for pre-post ROM and pain scale data. The use of Statistical version 14.0 was used for the analysis and p value of <0.05 was deemed significant. Results: Pain: This study found that for 91.9% of individuals participating in the intervention (n=1377), there was a reduction in lower back pain measured on the VAS pain scale, while for 5.2% (n=78) there was no change in pain, and for only 2.9% there was an increase in pain (n=44). ROM: All age groups were found to have increase range of motion in all movements from pre- intervention to post-intervention. Conclusion: The South African adaptation of the DBC protocol over the last 3 years has been successful in reducing pain and increasing ROM in all age group categories pre-intervention to post-intervention
Investigating the correlation between demographic and comorbidity profiles with chemotherapeutic toxicity experiences in early-stage breast cancer patients in a private medical oncology practice in South Africa
(University of the Witwatersrand, Johannesburg, 2024) Minns, Chantelle Pienaar; Booth, Zelna; Shaikh, Rubina; Padayachee, Neelaveni
Background: An estimated 24 million people will be diagnosed with cancer globally by 2050, with approximately 16.8 million expected to be residing in low- and middle-income countries. Breast cancer is one of the most prevalent types of cancer diagnosed in women worldwide and 23% of all diagnosed malignancies are attributed to breast cancer. The prevalence of chemotherapy-induced adverse drug reactions ranges globally between a vast 60 - 80% amongst patients, negatively impacting overall treatment outcomes. Aim of study: This study aimed to determine a potential correlation between demographic profiles and the presence of pre-existing comorbidities on the chemotherapy-related adverse effects experienced by patients with stage 0-III breast cancer at a private oncology centre in Gauteng. Furthermore, interventions applied by the oncologists to mitigate the adverse effects were investigated and reported adverse events were compared to the WHO VigiAccess Adverse Drug Reaction database. Methods: A quantitative, retrospective cohort analysis of patient charts from January 2018 to December 2019 at the private Sandton Oncology Centre was undertaken. The study sample size was 54 participants. Patient files were randomly selected. Demographic and comorbidity profiles, as well as the staging (0 – III) data were retrieved from patient medical charts, in accordance with the study inclusion criteria. Furthermore, the chemotherapeutic toxicities, experienced by patients, treated with a particular chemotherapeutic agent were reviewed. Interventions employed to alleviate toxicity were further recorded for data analysis (dose modifications, dose reductions, and premature discontinuation of oncology treatment). Descriptive statistics was analysed using pivot tables in Microsoft Excel. Inferential statistics was analysed with Stata software version 18. Ethical clearance was obtained before patient files were accessed and confidentiality of patient information was maintained throughout the study. Results: Most patients included in the study were white (57.4%), aged 50 – 59 years (29.6%), and diagnosed with stage II breast cancer (48.2%). Most of the patients had tumours which were oestrogen (66.7%) and progesterone positive (57.4%) and Human Epidermal Growth Factor Receptor 2 (HER2) negative (48.2%). The majority of patients, irrespective of ethnicity, received a combination of an anthracycline and cyclophosphamide followed by a taxane (51.8%). The most documented comorbidities were hypertension, obesity, dyslipidaemia, and diabetes. Of those patients reporting adverse effects, 77.8% reported adverse effects after the first cycle of chemotherapy. The chemotherapy-related adverse effects show similarity to the adverse effects reported on the World Health Organisation’s VigiAccess Adverse Drug Reaction database, particularly adverse effects of the digestive, integumentary, haematological and lymphatic systems. Conclusions: The number of comorbidities present increases with age. White patients with more comorbidities experienced more chemotherapy-related adverse effects. The majority of the patients for which dose reductions were implemented, experienced five or more adverse effects during their treatment. More than half of the termination of treatment cases were preceded by a dose reduction. No statistically significant correlation was found between any of the ethnic groups or age categories and the total number of adverse effects experienced. A statistically significant correlation was found between other comorbidities and the number of psychiatric adverse effects (p=0.014). Reported infections were significantly higher in patients with hypertension (p=0.043) and lymphatic system adverse effects were higher in patients with dyslipidaemia (p=0.017)
Breathing pattern dysfunction amongst patients with median sternotomy post hospital discharge: a cross- sectional study within a South African context
(University of the Witwatersrand, Johannesburg, 2024) Hurst, Samantha; Roos, Ronel
Introduction: Patients following cardiac surgery via median sternotomy surgical approach experience a deficit in chest wall expansion and respiratory muscle strength during hospital stay. To date, no study has assessed whether there is a long-term breathing pattern dysfunction (BPD) present in patients following cardiac surgery via median sternotomy surgical approach. Aim: To establish whether patients within the period of three months to one year post cardiac surgery via median sternotomy surgical approach still experience a BPD and, if so, to determine the risk factors to development of such a dysfunction. Methods: A cross-sectional observational study was conducted in a private hospital in Pretoria, South Africa from December 2022 - November 2023. Male and female patients between the age of 18-65 years who underwent an elective cardiac procedure via median sternotomy surgical approach were invited to participate. Participants were assessed once within the period of three months to one year post hospital discharge via questionnaires emailed to them and a telephonic video consultation. Outcome measures used included work- and health-related demographic questionnaires, the Physical Activity Vital Sign (PAVS), the Self-Evaluation of Breathing Questionnaire (SEBQ), The Nijmegen Questionnaire (NQ), the Breath Hold Time (BHT) Test, and the measures of upper and lower chest expansion (CE). Data were evaluated using descriptive and inferential statistics. Statistical significance was set at p<0,05. Results: The study population consisted of 52 participants, of which, most identified as male gender (59,60%, n=31) and underwent coronary artery bypass graft surgery (CABG) (51,90% ,n=27). The median age of participants was 57,00 (IQR 14,00) years and most participants presented with an elevated body mass index (28,90 kg/m², IQR 6,60). Return to work rate was established to have been 61,50% (n=32) with a median return to work time (RTWT) of six (IQR 4,00) weeks. Of the participants who returned to work, the majority (17,30%,n=9) worked in administrative occupations involving prolonged sitting (42,50%, n=17). The majority of participants scored positive in three of the outcome measures (51,90%, n=27) for BPD. A weak negative correlation existed between age and NQ and between age and SEBQ (r=-0.32, p=0,02). There was a weak negative correlation between length of hospital stay and lower CE (r= -0,30, p=0,03). There were weak positive correlations between PAVS aerobic scores and upper CE (r=0,33, p=0,02) ,lower CE (r=0,39,p<0,01) and BHT (r=0,29,p=0,04). There was a weak negative correlation between PAVS aerobic scores and SEBQ scores (r=-0,30,p=0,03). In terms of predictive values, being identified as male gender reduced the odds of developing a BPD in the psychophysiological dimension by 82%. Participants who underwent the surgery classified as “other” were 21 times more likely to score positive in the psychophysiological dimension of BPD than participants who underwent CABG, valve or mixed CABG and valve surgery. Participants who acquired cardiac complications were 11,67 times more likely to score positive in the psychophysiological dimension of BPD than participants who did not acquire complications or acquired other non-cardiac related complications. The absence of post-operative complications reduced the risk of developing a BPD in the psychophysiological dimension by 77%. Additionally, for every minute a patient partook in weekly aerobic exercise, the odds of developing a BPD in the psychophysiological dimension decreased by 1%. In terms of the biochemical dimension of BPD, participants who returned to work were 4,42 times more likely to score positive for BPD in this dimension. Conclusion: There is a high prevalence of long-term BPD amongst patients who underwent cardiac surgery via median sternotomy surgical approach. Factors found to increase the risk of developing BPD in a multidimensional context include the female gender, the type of surgery (particularly thymectomies and atrial septal defect repairs), cardiac post-operative complications and whether a participant has returned to work. Factors found to reduce the risk of developing BPD include the duration of weekly aerobic exercise and the absence of post-operative complications
Exercise dosages for the management of generalized anxiety disorder: A scoping review
(University of the Witwatersrand, Johannesburg, 2024) Leander, Natalie; Olivier, Benita
Objective: This review was conducted to map the extent of evidence relating to the dosage of exercise for anxiolytic effect, in youth and adolescents with Generalized Anxiety Disorder (GAD). Introduction: Exercise is known for its benefit to people living with depression and anxiety in adult populations. Less is known about the differences in exercise prescriptions used for the management of anxiety subtypes in younger populations. The rationale for this topic in adolescents and youths, living with GAD was to ascertain the extent to which this cohort has been studied regarding the use of exercise in the treatment of anxiety and which dosages were used. Inclusion criteria: All studies with participants aged 10-24 years of age with a GAD diagnosis, were considered, where exercise was used as part of the management of their anxiety. No restrictions were placed on study types. A scoping review was performed using the JBI methodology. Databases searched included Pubmed, PEDro, Cochrane database of systematic reviews and Cinahl Ultimate along with grey literature databases. No time restrictions were applied, and all types of research articles were considered. The charted data was tabulated using a modified JBI data extraction instrument. The initial result of 728 results was reduced to four studies that met with inclusion criteria. The final four studies had populations in the upper range of between 18 to 24 only. No applicable data was found in the 10 to 17-year age range. The exercise types used in these four studies were treadmill running, Pilates, lower limb strengthening and dynamic cycling. Two studies incorporated a single bout of vigorous treadmill running for 30 minutes. One study did a single bout of beginner Pilates for 30 minutes and the last study used lower limb strengthening and dynamic cycling biweekly for six weeks. The literature on exercise dosage for the management of GAD in adolescents and youth is severely limited. Data on exercise for specific subtypes of anxiety in adolescents and youth seems to be limited in general as well. This is an important area for research as anxiety starts in early childhood and GAD in particular has a peak age of onset of 15 years. It seems feasible to try and approach anxiety in youth and adolescents with non-invasive therapies such as exercise but there is a definite gap in the literature regarding its use in managing GAD
Running-related injuries and risk factors among runners in Soweto township clubs, Johannesburg
(University of the Witwatersrand, Johannesburg, 2024) Masilana, Masocha Vusi; Kunene, Siyabonga
The surge in running's popularity globally has brought about an increase in running-related injuries (RRIs), particularly prevalent in sub-Saharan Africa, including South Africa's urban township of Soweto, where physical inactivity and non-communicable diseases pose significant public health challenges. This necessitates targeted research on RRIs in the region to understand the specific external and internal risk factors. The study aimed to determine the prevalence and risk factors for RRIs among recreational and professional runners in Soweto, Johannesburg. The study utilised a cross-sectional design to determine the prevalence and risk factors associated with RRIs, allowing for an efficient one-time data collection from a large sample. Runners from Soweto township was included in the study. A data collection tool in the form of a self-administered questionnaire was employed, utilising the RedCap online platform for administration. A structured analysis plan was implemented using STATA software, with an additional data processing phase in Excel to enhance the clarity and readability of results, including the customisation of charts and graphs to communicate the findings effectively. Descriptive and inferential statistics were obtained. Demographic analysis revealed a higher prevalence of female runners at the beginner level (55%, n=17), with a significant association between advancing age and injury risk. Among professional runners, the distance covered emerged as a significant risk factor, particularly for medium and long-distance runners (odds=2.07, p=0.05 and odd = 3.01, p =0.03, respectively). The frequency of training sessions demonstrated varying degrees of risk for both novice and professional runners. Additionally, terrain-specific analysis highlighted the elevated risk of injuries for beginners on varied terrain relative to professional runners. Statistical findings included significant odds ratios for female runners (odds = 0.75, p =0.05), age over 25 among beginners (odds = 1.56, p = 0.031), medium distance running among professionals (odds = 2.07, p = 0.050), and varied terrain among beginners (odds = 1.76, p = 0.006). This study provides critical insights for tailoring injury prevention and management techniques, particularly for runners of various levels. It emphasises the importance of individualised treatments by stressing nuanced damage patterns between beginners and professionals. The heightened risk on varied terrain for beginners and the unique implications of sports engagement on injury risk for professionals are noteworthy findings. These findings guide tailored prevention strategies, recognising the varied character of RRIs and addressing unique needs at various career stages, with possible policy and future research implications.
Mode of delivery, analgesic, and neuromusculoskeletal profile of women developing new onset lower back pain postpartum
(University of the Witwatersrand, Johannesburg, 2024) Steyn, Joretha
The aim of this cohort study, a longitudinal study that follows participants over a period, was to establish the profile of women developing lower back pain (LBP) postpartum by investigating the association between LBP and the mode of delivery, analgesia used and the neuromusculoskeletal structures involved. A baseline assessment was done on 16 participants, four were excluded as per the exclusion criteria, with outcome measures such as the Oswestry LBP disability questionnaire and the visual analogue scale (VAS) at 24 weeks gestation and a follow up assessment at six- and 12-weeks postpartum. Irrespective of the analgesia used during labour (epidural, combined spinal and epidural (CSE), general anaesthesia or no analgesia) or the mode of delivery, be it natural, an elective caesarean section or an emergency caesarean section, 50% (n=6) had pain at six weeks postpartum and 14% (n=7) at 12 weeks postpartum. The VAS and Oswestry LBP disability questionnaire averaging 4/10 and 12.6% respectively. It should be noted that the 14% (n=7) that had pain at 12 weeks had a scheduled caesarean section done under general anaesthesia which leads us to agree with Eisenach, et al., (2013) that labour itself does have a protective physiological mechanism against developing pain postpartum. It is recommended that a future study should extend the time frame of data collection to two to three years to ensure a larger sample size to get a more significant and clearer picture of the development of LBP postpartum and the factors or structures involved. This in turn can ensure a more comprehensive preventative strategy to be researched to decrease the development of LBP postpartum.
Impact of a rural context in Kwazulu Natal on primary caregiver's management of pain innon-communicating children with severe neurological impairment
(University of the Witwatersrand, Johannesburg, 2024) Pretorius, Jeanette; Franzsen, Denise
Untreated pain is known to have negative consequences on the development and wellbeing of “non-verbal” children with severe neurological impairment (SNI). Healthcare workers and caregivers must ensure that pain is managed in this population, even though pain may be difficult to assess. Occupational therapists need to understand how context affects the management of pain experienced by a child with SNI, as well as its impact on the care of the child. This study determined how a rural KwaZulu Natal context impacted how primary caregivers recognized and manage pain and the care of their child with SNI. Methods: A multiple descriptive, embedded case study design using a demographic and pain questionnaire, with cross sectional design. There were nine respondents’ qualitative and quantitative information content analysis and descriptive statistics were used to report. Results: Financial, environmental, emotional and physical strain factors associated with the rural context were identified may be adding to the burden of care and affecting the occupational performance of the child with SNI and their caregiver. Specific difficulties included limits in access to clean running water, the practice of bed sharing and poor infrastructure affecting access to healthcare facilities. Primary care givers also mentioned their other responsibilities in the house and the physical strain of caring for a child with SNI affected them and their child. Despite this, all primary care givers were able to recognise and act when their child was in pain and relied on crying duration and intensity as a reliable sign of pain in their child. All primary care givers were confident in their ability and method of recognising and addressing pain in their child with SNI. More experienced primary caregivers used fewer signs to recognise when their child with SNI was in pain. Conclusions: A rural African context is associated with barriers and opportunities for the care, the recognition- and management of pain in children with SNI. More research related to supporting participation and occupational performance by addressing the effects of pain in children with SNI on the child and the primary caregiver living in rural contexts is required
The psychosocial work environment of primary health care nurses in the Northern Sub-DistrictCity of Ekurhuleni
(University of the Witwatersrand, Johannesburg, 2024) Motsumi, Theodora
Background: Studies have shown that nurses in general are exposed to higher psychosocial work environment challenges primarily manifested as work-related stress, burnout, depression, and fatigue. Hence, the need to investigate how PHC nurses experience their psychosocial work environments in the northern sub-district of the City of Ekurhuleni. Objectives: To describe the psychosocial work environment as well as determine the association between the socio-demographic data and domains that score as negatively and positively indicative of the perceived psychosocial work environment. Method: A descriptive cross-sectional survey design was used for this study, and data were collected using a self-administered questionnaire, the Copenhagen Psychosocial Questionnaire II (COPSOQ II). Data analysis: Firstly, STATA 18 (Standard Edition) was used for demographic and COPSOQ II scale analysis. Secondly, the open-ended question was analyzed through the sentiment analysis process using Microsoft Excel 2021, Office 365 add-on package Azure Machine Learning to identify the themes and determine the emotional tone of the responses which were classified as positive, negative or neutral. Lastly, Bivariable analysis was conducted using a Pearson Chi-square test (χ² test) and a Fisher’s Exact test for the purpose of establishing associations. Results: A total number of (n=80) PHC nurses participated in the study. Most were females (87.5%) and (60%) have more than ten years of professional nursing experience. Quantitative work demands, Work pace, Emotional work demands, Work/ life conflict as well as Burnout and stress are the dimensions that were Red coded, rated as needing immediate care and are indicative of poor care. Age was associated with Job demands and Work/individual interface. Years of experience was associated with interpersonal relationships and Leadership, and Health and wellbeing. Three themes emerged from the sentiment analysis of the open-ended question namely; professional recognition and job satisfaction, workload and staffing issues, and workplace environment and support. The results further showed that (76%) of the respondents expressed negative sentiment regarding the psychosocial environment and the average sentimental score was 0.26 indicating highly negative perception about the psychosocial environment. Conclusion: The results serve as a baseline for a study on psychosocial environment and can be used to inform the development of a more comprehensive in-depth psychosocial research study, to develop and implement sustainable and effective healthy workplace programs to meet the psychosocial needs of PHC nurses and other health care workers
The emergency management of patients who have experienced sexual violence: an integrative literature review
(University of the Witwatersrand, Johannesburg, 2023) Quiroga, Neil Dylan
Background: Sexual violence is endemic in many countries, and particularly in South Africa.. Over the past few years there have been several advancements in the care for patients who have experienced sexual violence. However, the care available in resource limited settings and in South Africa, remains inconsistent and often inadequate. Purpose of the Study: To synthesize the current evidence based practice in the emergency management of patients who have experienced sexual violence; and to review which advancements could be feasible in a resource limited setting, and in the South African context. Methods: This study conducted an integrative literature review on the emergency management of patients who experience sexual assault, in order to synthesise the current literature. The research is structured on Whittemore and Knafl’s framework, and utilizes their five stages of an integrative review: problem identification, literature search, data evaluation, data analysis, and presentation. The following databases were searched: Cochrane library, EBSCOhost (CINAHL; ERIC and MEDLINE), PubMed, ScienceDirect, Wiley online library and Psycinfo. 2142 articles were assessed fully for eligibility, and a total of 47 articles were included in the integrative review. The literature search was conducted over a period of 4 months. Thematic analysis of the 47 articles was then conducted using MaxQDA (Qualitative Coding Software). A conductive coding approach was used, based on grounded theory. Results: Eight main themes, and thirty four subthemes, emerged from the data that spoke directly to the research question and objectives. The eight major themes were: Screening patients for sexual violence; emergency medical care for survivors; forensic care; mental health care; follow up care and services; technological aids to augment care; structural or organization aspects affecting care; and health care worker factors that affect care for survivors. Conclusion: The study strongly recommends integrating trauma informed care into every aspect of care for survivors of sexual violence in South Africa. The study also recommends implementing: screening of patients for various forms of sexual violence; quality improvement drivers such as order sets and clinical pathways; and nurse driven innovations in pro-active follow up services and new mental health care interventions
Private Sector Health Care Users’ Criteria for Choosing Maternity Services In A District In Mpumalanga
(University of the Witwatersrand, Johannesburg, 2024) Clay, Nadia Susan; Armstrong, Sue
Currently, maternity care in the public sector in South Africa is differentiated according to the level of care required. There is also a substantial difference in resource availability between the public and private healthcare sectors. Urban area healthcare users with medical insurance have a choice of private or public sector facilities and even a choice between midwifery-led care and obstetrician led care. This will no longer be the case once the National Health Insurance (NHI) is introduced. Currently, private healthcare users in rural areas have fewer choices due to the lack of facilities. This group of healthcare users therefore has a unique understanding and experience of the quality and types of service offered in the public and private sector. Their perspective will be useful in determining the priorities for establishing equitable maternity services as envisaged by the NHI. By comparing their perspectives to those of healthcare users of the public sector maternity services, it will be possible to establish whether differences occur and, at a later stage, to start planning services that meet the needs of both the public and the private sector healthcare users. This study sought to answer the research question, “Do private sector healthcare user’s criteria for choosing a maternity service differ from those of public sector users?” A multi-method qualitative study was used. Phase 1 included a scoping review which determined the criteria used to measure patient satisfaction in the public maternity services in sub-Saharan Africa. Phase 2 of the study included semi-structured interviews of nineteen (19) women of childbearing age to determine the criteria that private sector users use when choosing a maternity service to meet their needs and aspirations. The scoping review provided the a priori codes for phase 2 of the study. Using the a priori codes from the scoping review, a template analysis was conducted in phase 2. The findings of this study indicated that all women, irrespective of social class, culture or socio-economic status have similar needs and preferences and would use those similar criteria for choosing a birthing facility, should they be given that choice. The study emphasised that women need caring, responsive midwives to be present at their birth together with a birth companion of their choice in an accessible, clean and comfortable environment
Guidelines for the implementation of blended learning in a nursing college campus in Gauteng: a mixed methods study
(University of the Witwatersrand, Johannesburg, 2024) Maré, Magdalena Elizabeth; Armstrong, Sue
The purpose of the study is to develop guidelines on how a nurse educator can best be prepared to implement blended learning in a Nursing Education Institution in Gauteng. The readiness of nursing students and nurse educators in a nursing education institution in Gauteng was determined to serve as a point of reference for the development of guidelines to support nurse educators to implement blended learning in the institution. Blended learning is the thoughtful integration of different instructional methods that contain face to face on online components. It enhances the educational experience for nursing students, preparing them to meet the challenges of modern health care and promoting lifelong learning. The methodology used was a mixed method study, combining a quantitative survey using the Blended Learning Readiness Engagement Questionnaire (BLREQ®) to determine readiness for blended learning amongst nursing students and nurse educators, and two focus groups with nursing education managers and nurse educators respectively. The focus groups were done to determine how best nurse educators can be supported to offer blended learning in the Nursing education institution. The Community of Inquiry framework was used to analyse the data from the focus groups and the data from Section C of the BLREQ®. According to the survey, both nursing students and nurse educators perceived themselves as ready for the implementation of blended learning, although there are gaps in their technical abilities and ability to navigate online environments. The qualitative data revealed that both nursing students and nurse educators need support and guidance for the implementation of blended learning. Nursing education managers expressed that nursing educators are still using traditional methods of teaching and that they need to be supported to use innovative teaching methods such as blended learning through regular skills development sessions. Nurse educators and students also indicated that they are not confident in participating in online platforms and discussions and that they need orientation and support navigating online platforms and the current learner management system. Although both nursing students and nurse educators see themselves as having the basic digital skills, they indicated a need for training in spreadsheet, presentation, and online communication software as well as collaborative cloud computing. The availability of technology infrastructure and lack of resources for the successful implementation of blended learning in the Nursing Education Institution were identified by nursing education managers, educators, and students. Guidelines were developed to assist the nursing education managers, nurse educators and students to address the gaps identified and to orientate new students and nurse educators to navigate the blended learning environment to assist them to adapt to new technologies and ways of learning and teaching
Use of probiotics in community pharmacy in South Africa: a survey of pharmacist attitudes, perceptions and knowledge
(University of the Witwatersrand, Johannesburg, 2024) Kim, Yedam; Orchard, Ané
There has been a substantial increase in the consumption of probiotics in the last decade in South Africa. Pharmacists, as experts in the field of medicine, play a crucial role in educating both patients and other healthcare professionals on the appropriate use of probiotics in the healthcare setting. While there are several studies related to the use of probiotics, such as the study conducted among community pharmacists to explore their knowledge, attitudes, and practices regarding complementary and alternative medicines in South Africa, there is a gap in the literature regarding the knowledge, attitudes, and perceptions of qualified practicing pharmacists in South Africa regarding probiotic use. The findings of this study provide information for evaluating the current state of awareness and understanding regarding probiotics within the pharmacist community, offering a foundation for potential interventions and educational initiatives. A cross-sectional, descriptive-analytical study was conducted in community pharmacies across South Africa. Of the 476 study respondents, 237 were included in the final analysis, as 239 surveys were incomplete. Among the respondents, 18.5% demonstrated a good level of knowledge about probiotics, while 11.3% demonstrated a poor level of knowledge (Mean ± SD =13.81 ± 2.8). This finding demonstrated a lower knowledge level compared with similar studies conducted in other regions, such as Asia and the United States of America. These findings highlight a potential gap in knowledge among the respondents regarding the use of probiotics. Half of the respondents (49.9%) displayed positive attitudes toward probiotics (Mean ± SD = 43.33 ± 8.9) and 47.6% of the respondents displayed positive perceptions of probiotics (Mean ± SD = 32.14 ± 3.7). A significant association of knowledge of probiotics with biological sexes (X2 = 39.2132, p < 0.05) was found. There was a statistically significant difference in the demographics of respondents and their attitudes towards probiotics, including geographical region (X2 = 300.629, P<0.05), biological sex (X2 = 95.164, p < 0.05), age (X2 = 248.008, p < 0.05), highest degree obtained (X2 =191.428, p < 0.05), and the university from which they graduated (X2 = 417.775, p < 0.05). Statistically significant difference in the demographics of respondents and the perceptions of probiotics was found, including geographical region (X2 = 170.161, p < 0.05), age (X2 =52.378, p < 0.05), and the university from which they graduated (X2 = 238.514, p < 0.05. In this study, a significant but weak correlation between knowledge and attitude was identified (r = 0.1537, p = 0.0179). Correlation between attitudes and perception was also significant but weak (r = 0.3214, p = 0.000) and there was no statistically significant correlation between knowledge-perceptions variables (r = 0.0092, p = 0.8879). The study has identified limited knowledge regarding the use of probiotics among respondents, despite their positive attitudes and perceptions towards the use of probiotics. The study also has emphasized the complexity of factors influencing individuals' knowledge, attitudes and perceptions regarding probiotics. This study recommends further educational initiatives to investigate relationship between knowledge, attitudes and perceptions of pharmacists on the use of probiotics in South Africa
Targeted nanosystems for tuberculosis pericarditis interventions
(University of the Witwatersrand, Johannesburg, 2024) Ayodele, Simisola Ayobami; Kumar, Pradeep; Choonara, Yahya Essop
Tuberculosis (TB) maintains its infamous status regarding its detrimental effect on global health, causing the highest mortality by a single infectious agent. It presents as the second most lethal infectious disease after HIV/AIDS. The presence of resistance and immune-compromising disease favors the disease in maintaining its footing in the health care burden despite various anti-TB drugs. The main factors contributing to resistance and difficulty in treating disease include prolonged treatment duration (at least 6 months) and severe toxicity, which further leads to patient non-compliance, and thus a ripple effect leading to therapeutic non-efficacy. The efficacy of new regimens demonstrates that targeting host factors concomitantly with the Mycobacterium tuberculosis (M.tb) strain is urgently required. Due to the huge expenses and time required of up to 20 years for new drug research and development, drug repurposing may be the most economical, circumspective, and conveniently faster journey to embark on. Host-directed therapy (HDT) will dampen the burden of the disease by acting as an immunomodulator, allowing it to defend the body against antibiotic-resistant pathogens whilst minimizing the possibility of developing new resistance to susceptible drugs. Repurposed drugs in TB act as host-directed therapies, acclimatizing the host immune cell to the presence of TB, improving its antimicrobial activity and time taken to get rid of the disease, whilst minimizing inflammation and tissue damage. Anti-TB drugs incorporated in nanosystems may reduce side effects by delivering the drug selectively into infection reservoirs such as macrophages, which may assist in clearing the TB bacilli faster and reducing the duration of therapy. Tuberculosis pericarditis (TBP) is a type of extrapulmonary tuberculosis caused by the retrograde lymphatic spread of the bacilli from lymph nodes. TBP is known to have a high burden in southern Africa due to the high prevalence of HIV and its contribution to TBP. Traditional anti-TB drugs have poor permeation across the pericardium, making TBP a difficult disease to treat with high mortality. Rapid HPLC methods were initially established for the detection and quantification of isoniazid and pyrazinamide at a physiological pH (pH 7.4). These methods were subsequently used for the detection and quantification of both compounds in the ex vivo pericardium studies. Although both drugs diffused across the pericardium, only isoniazid has anti-tubercular effects at physiological pH. Both drugs permeated across the pericardium at pH 7.4, but only isoniazid has anti-tubercular effects at this pH. Bedaquiline is known to shorten the duration of therapy but has limitations e.g., poor solubility and adverse effects such as prolongation of QT interval, causing careful use and close monitoring of its adverse effects and possible drug interactions. In this study, bedaquiline was incorporated into an inherently targeted nanosystem made of mannan (host-directed therapy) for improved permeation of the drug across the pericardium. The bedaquiline-loaded mannan-chitosan oligosaccharide lactate nanoparticles were prepared by a one-step ionic gelation probe sonication method. A PermeGear 7-in-line flow-through system was used for the ex vivo diffusion studies across porcine and human pericardium. The nano gel was loaded into the donor compartment. Phosphate buffer saline (pH 7.4 with 0.2% sodium lauryl sulphate) was pumped through the receptor compartments at 1.5 ml.h-1 (37 °C). Samples were collected every 2 h for 24 h and analyzed via HPLC. Bedaquiline loaded nanoparticles with particle size and potential of 192.4 nm and 40.5 mV, respectively, were synthesised. The chitosan-mannan bedaquiline loaded nanoparticles had an encapsulation efficacy of 98.7% and drug loading of 0.6%. Diffusion data of bedaquiline in the nanosystem indicated a flux of 2.889 and 2.346 μg.cm - 2. min -1 for porcine and human pericardium, respectively, as compared to 0.991 μg.cm-2.min-1 and 1.1578 μg.cm-2.min-1 for isoniazid and pyrazinamide, respectively. The permeation of the nanosystem indicated a consistent and linear diffusion pattern across both porcine and human pericardium, additionally approving the porcine pericardium as a great comparable tissue to human tissue for pericardial studies. The nanosystem, therefore, presents an exceptional direction for the treatment of tuberculosis pericarditis with prospectively minimized systemic side effects and host-directed therapy

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