Electronic Theses and Dissertations (Masters)
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Browsing Electronic Theses and Dissertations (Masters) by School "School of Therapeutic Sciences"
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Item A retrospective review on the utilisation of meropenem in a tertiary hospital setting(University of the Witwatersrand, Johannesburg, 2024) Mohun, ShameedaIntroduction: 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 issueItem A Survey of the Delivery of Clinical Services in Independent Community Pharmacies in South Africa(University of the Witwatersrand, Johannesburg, 2024) Ismail, Tahir; Khan, RazeeyaIntroduction 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 pharmaciesItem An evaluation of the effects of metal complexes on lung cancer cell lines(University of the Witwatersrand, Johannesburg, 2024) Mangena, Zanele; Harmse, LeonieLung 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 propertiesItem Antibacterial stewardship practices in South Africa during the COVID-19 era: A retrospective review(University of the Witwatersrand, Johannesburg, 2024) Spinickum, Logan Jade; Leigh-de Rapper, StephanieBackground: Several mechanisms may facilitate and steer the development of antibiotic resistance patterns. The most prominent driver associated with antibiotic resistance has been indicated as inappropriate use or consumption of antibiotics. The sudden emergence of Coronavirus Disease 2019 (COVID-2019) changed the conventional practices related to drug utilisation through the repurposing of antibiotics. Despite the implementation of antibiotic stewardship programs, the pressure that COVID-19 placed on healthcare systems resulted in poor prescribing and antibiotic review practices, potentially exacerbating antibiotic resistance. Moreover, the public health sector faces various challenges that make it difficult to consistently assess and quantify antibiotic usage; while providing quality review, feedback, and intervention, especially in low- and-middle-income countries like South Africa. As a result, there is a paucity of information concerning antibiotic utilisation in the public healthcare sector, even following the emergence of the COVID-19 pandemic. It is essential to determine the extent of antibiotic use to improve antibiotic utilisation, patient outcomes and stimulate viable policies and initiatives to strengthen public healthcare drug surveillance amidst the challenges of increased infectious diseases, resistance, and health personnel shortages. Aim of study: The aims of the study were to determine, analyse and compare antibiotic consumption amongst intensive care unit (ICU) patients admitted in a Gauteng public hospital during the pre-COVID-19 era and commencement of the COVID-19 era. Methodology: A retrospective cross-sectional data analysis of 335 medical files of ICU patients hospitalised in a Gauteng Provincial Tertiary Hospital (GPTH) between January 2017 and December 2021. Descriptive statistics were used to examine patient characteristics and antibiotic prescribing variables. Results: The study found that the more frequently prescribed antibiotics were amoxicillin/clavulanate (pre-pandemic = 31.99%; COVID-19 = 38.43%), followed by ceftriaxone (pre-pandemic = 15.44%; COVID-19 = 14.55%), piperacillin/tazobactam (pre-pandemic = 11.40%; COVID- 19 = 8.58%) and azithromycin (pre-pandemic = 7.73%; COVID-19 = 19.78%). Common bacterial pathogens detected in both periods included Acinetobacter baumannii (pre-pandemic = 29.2%; COVID-19 = 20.9%), Enterobacter cloacae (pre-pandemic = 10.4%;COVID-19 = 14.0%), Escherichia coli (pre-pandemic = 22.9%; COVID-19 = 25.6%), and Klebsiella pneumoniae (pre-pandemic = 25.0%; COVID-19 = 18.6%). Resistance was predominantly observed in ciprofloxacin (pre-pandemic = 11.4%; COVID-19 = 12.9%), piperacillin/tazobactam (pre-pandemic = 12.7%; COVID-19 = 0.1%), cefotaxime (pre-pandemic = 13.2%; COVID-19 = 14.7%), and cefepime (pre-pandemic = 12.7%; COVID-19 = 11.2). Resistance to commonly prescribed antibiotics observed a decrease trend moving from the pre-pandemic period into the COVID-19 pandemic. Conclusion: The macrolide and penicillin (in combination with beta-lactamase inhibitor(s)), classes demonstrated an increase in prescribing and use across the pre-pandemic period transitioning into the COVID-19 pandemic. While overall resistance observed a decline moving into the COVID-19 pandemic. However, “Watch” category antibiotic resistance increased slightly. An increase in prescribing and use of macrolides coupled with an increase in “Watch” category antibiotic resistance, highlights the need for improved antibiotic stewardship programs in public healthcare and pathogen-directed prescribing, to combat inappropriate and unnecessary use of antibiotics.Item Brain concentrations and the neurochemical effects of passively administered fluoxetine in Flinders sensitive line rat offspring(University of the Witwatersrand, Johannesburg, 2023) Steyn, Stephanus FrederikBackground: 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 periodItem 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, RonelIntroduction: 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 complicationsItem Design and evaluation of a non-opioid tripartite release tablet for chronic inflammatory pain(University of the Witwatersrand, Johannesburg, 2024) Mazarura, Kundai Roselyn; Van Eyk, Armorel; Choonara, Yahya E.; Kumar, PradeepFormulation-based approaches towards curbing the prescription opioid crisis include the discovery and development of non-opioid analgesics such as the novel benzyloxy- cyclopentyladenosine (BnOCPA). A more expedited approach involves the development of combinatorial systems of already existing non-addicting analgesics to tap into unexplored synergistic potentials. Despite the recent advances in drug delivery systems, tablets still hold the position of being the most widely used oral dosage form, particularly in the management of chronic ailments; it is cost-effective, non-invasive, and does not require administration expertise. Challenges in the production of complex geometry combinatorial, multi-drug tablets remain to some extent enigmatic to pharmaceutical researchers, hence the steady paradigm shift from traditional compression to 3-dimensional printing. Although it is superior in multiple aspects, the technique is still in its nascent stages with limited information on regulatory guidelines. Therefore, the aim of this work was to design and develop a non-opioid tripartite controlled- release tablet for efficient chronic inflammatory pain management. Because adherence to adjunct gastroprotective agents (GPAs) in non-steroidal anti-inflammatory drugs (NSAIDs) users has been established to be suboptimal, esomeprazole magnesium trihydrate (ESM) was added to the drug delivery system (DDS). The rationale behind the design was based on inherent drug properties, target release sites, desired therapeutic effects, and allowance for drug release manipulation, therefore a tablet was assembled, constituting an immediate- release top layer formulation of 250 mg paracetamol (PAR) for an early onset of analgesia; a cup layer for the delayed and retarded release of 100 mg of diclofenac sodium (DS) and 250 mg of PAR in tandem, and lastly a core containing a press-coated 20 mg ESM pill. A reproducible and efficient Reverse-Phase High-Performance Liquid Chromatographic (RP-HPLC) method was developed and validated for the simultaneous detection of the APIs over the concentration ranges studied. Deleterious drug-excipient incompatibilities were ruled out through pre-formulation investigations by FTIR, DSC, and TGA analyses. Combining both wet and dry granulation methodologies; the chosen formulation and polymers (7.5% hydroxypropyl methylcellulose (HPMC) K15M, 25.3% eudagrit L (EL) 100-55, and 10.5% croscarmellose sodium (CCS)), while considering the quality target product profiles (QTPPs), critical process parameters (CPP), and critical material attributes (CMAs), resulted in the development of a pragmatic tablet delivering fifty percent of the PAR dosage in the initial 30 minutes, with a cumulative release of 95.0% ± 0.08% and 94.9% ±3.87% for DS and ESM, respectively. Through in-process quality control tests, the validity of the manufacturing process was confirmed, with all results falling within pharmacopeial specifications. The release mechanism of PAR and DS from the cup after the 2-hour mark distinctly followed the Hixson-Crowell model where the geometrical characteristic of the cup was maintained with surface erosion. Visuals from scanning electron microscopy (SEM) analysis obtained prior to and during dissolution, confirmed hydration gravimetric analysis results as well as bulk and surface erosion mechanisms. The obtained ex vivo analysis results showed retarded permeation rates of the tabletted APIs compared to the APIs in their pure state. Therefore, it is imperative to consider improving the existing models employed for ex-vivo permeability studies of tableted formulations, with a particular focus on exploring the impact of excipients/polymers on drug permeationItem Essential oil compounds in combination with conventional antibiotics for dermatology(University of the Witwatersrand, Johannesburg, 2024) Simbu, Shivar Bram; Van Vuuren, SandySkin 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.Item Exercise dosages for the management of generalized anxiety disorder: A scoping review(University of the Witwatersrand, Johannesburg, 2024) Leander, Natalie; Olivier, BenitaObjective: 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 GADItem 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, SueThe 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 teachingItem 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, DeniseUntreated 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 requiredItem The impact of lower limb amputation on quality of life: a study done in the Johannesburg Metropolitan area, South Africa(University of the Witwatersrand, Johannesburg, 2010-01-29T07:15:06Z) Godlwana, Lonwabo L.Background: The impact of non-traumatic lower limb amputation on participant’s quality of life (QOL) is unknown. In an effort to provide better care for people with lower limb amputation, there is a need to first know the impact of this body changing operation on people’s quality of life. Aim of the study: To determine the impact of lower limb amputation on QOL in people in the Johannesburg metropolitan area during their reintegration to their society/community of origin. Objectives: 1. To establish the pre-operative and post-operative: QOL of participants (including the feelings, experiences and impact of lower limb amputation during the time when they have returned home and to the community). The functional status of participants. Household economic and social status of these participants. 2. To establish factors influencing QOL. Methods: A longitudinal pre (amputation) test –post (amputation) test study utilized a combination of interviews to collect quantitative data and in-depth semi-structured interviews to gather qualitative data. Consecutive sampling was used to draw participants (n=73) for the interviews at the study sites pre-operatively. The three study sites were Chris Hani Baragwanath Hospital, Charlotte Maxeke Johannesburg General Hospital and Helen Joseph Hospital. Participants were then followed up three months later for post-operative interviews and key informants were selected for in-depth interviews (n=12). Inclusion criteria: Participants were included if they were scheduled for first time unilateral (or bilateral amputation done at the same time) lower limb amputation. The participants were between the ages of 36-71 years. Exclusion criteria: Participants who had an amputation as a result of traumatic or congenital birth defects were excluded from the study. Participants with comorbidities that interfered with function pre-operatively were not included. Procedures: Ethics: Ethical clearance was obtained from the Committee for Research on Human Subjects at the University of the Witwatersrand and permission was obtained from the above hospitals. Participants gave consent before taking part in the study. Instrumentation: A demographic questionnaire, the EQ-5D, the Modified Household Economic and Social Status Index (HESSI), the Barthel Index (BI) and semi-structured in-depth interviews were used. Data collection: Participants were approached before the operation for their preoperative interviews using the above questionnaires and then followed up postoperatively using the same questionnaires and some were selected to participate in semi-structured in-depth interviews three months later. Pilot study: The demographics questionnaire and the modified HESSI were piloted to ensure validity and reliability. iii Data analysis: Data were analyzed using the SPSS Version 17.0 and STATA 10.0. The significance of the study was set at p=0.05. All continuous data are presented as means, medians, standard deviations and confidence intervals (CI 95%). Categorical data are presented as frequencies. Pre and post operative differences were analyzed using Wilcoxon Signed-rank test. A median regression analysis (both the univariate and multivariate regression) was done to establish factors influencing QOL. Pre and post operative differences in the EQ-5D items and the BI items were analyzed using Chi square/Fischer’s exact depending on the data. Data were pooled for presentation as statistical figures in tables. Both an intension to treat analysis and per protocol analysis were used. A grounded theory approach was used to analyze the concepts, categories and themes that emerged in the qualitative data. Results: Twenty-four participants (33%) had died by the time of follow up. At three months, n=9 (12%) had been lost to follow up and 40(55%) was successfully followed up. The preoperative median VAS was 60 (n=40). The postoperative median VAS was 70. The EQ-5D items on mobility and usual activities were reported as having deteriorated significantly postoperatively (p=0.04, p=0.001respectively) while pain/discomfort had improved (p=0.003). There was no improvement in QOL median VAS from the preoperative status to three months postoperatively The preoperative median total BI score was (n=40). The postoperative median total BI score was 19. There was a reduction in function (median BI) from the preoperative status to three months postoperatively (p<0.001). The ability to transfer was improved three months postoperatively (p=0.04). Participants were also found to have a decreased ability to negotiate stairs (p<0.001). Mobility was significantly reduced three months postoperatively (p=0.04). During the postoperative stage (n=40), 38% of the participants were married. Most (53%) of the participants had no form of income. The highest percentage of participants in all instances (35%) had secondary education (grade10-11), while 25% had less than grade 5. Only one participant was homeless, 18% lived in shacks, 55% lived in homes that were not shared with other families. People with LLA in the Johannesburg metropolitan area who had no problem with mobility preoperatively (EQ-5D mobility item), who were independent with mobility (BI mobility item) preoperatively, who were independent with transfer preoperatively (BI transfer item) had a higher postoperative quality of life (postoperative median EQ-5D- VAS) compared to people who were dependent or had problems with these functions preoperatively. Being females was a predictor of higher reported quality of life compared to being male. Emerging themes from the qualitative data were psychological, social and religious themes. Suicidal thoughts, dependence, poor acceptance, public perception about body image, phantom limb related falls and hoping to get a prosthesis were reported. Some reported poor social involvement due to mobility problems, employment concerns, while families and friends were found to be supportive. Participants had faith in God. Conclusion: Participants’ QOL and function were generally scored high both preoperatively and postoperatively but there was a significant improvement in QOL and a significant reduction in function after three months although participants were generally still functionally independent. Good mobility preoperatively is a predictor of good QOL postoperatively compared to people with a poor preoperative mobility status. Generally, most participants had come to terms with the amputation and were managing well while some expressed that they were struggling with reintegration to their community of origin three months postoperatively with both functional and psychosocial challenges.Item Investigating the attitudes of physiotherapists about telerehabilitation and their opinions on its feasibility in South Africa(University of the Witwatersrand, Johannesburg, 2022) Thomas, TyllaBackground: Telerehabilitation has not been a permitted nor been a focus in healthcare in South Africa. There is little awareness, knowledge, and skill amongst physiotherapists on how to conduct effective telerehabilitation. However, this is not the case globally, where telerehabilitation has been proven effective in the treatment of patients with various conditions. Advances in telerehabilitation worldwide are occurring daily but there is scarce literature on telerehabilitation in South Africa. Due to Covid-19, the HPCSA has granted permission to conduct telehealth, however, numerous barriers first need to be overcome for telerehabilitation to become a common therapeutic practice. The attitudes of physiotherapists on telerehabilitation and its feasibility have not been investigated and hence the current use, or willingness to use, is unknown amongst the South African population. Aim: To investigate the attitudes of physiotherapists and their opinions on the feasibility of telerehabilitation in daily practice in South Africa. Methods: This quantitative, cross-sectional study included 356 physiotherapists belonging to the SASP, recruited through convenience sampling. An electronic self-reported questionnaire was developed from existing literature and other exiting questionnaires e.g. the Physiotherapy Mobile Acceptance Questionnaire (PTMAQ) (Blumenthal, Wilkinson, and Chignell, 2018). The questionnaire was emailed to all physiotherapists belonging to the SASP and they could voluntarily answer it. Descriptive data analysis was conducted to describe the demographic profile of physiotherapists and to determine their attitudes on telerehabilitation as well as the feasibility thereof in South Africa. One-Way ANOVA (analyses of variance) was used to establish a relationship between participants’ demographics and their attitudes and feasibility 2 regarding the use of technology for rehabilitation in South Africa. The study obtained ethical clearance from the Human Research Ethics Committee (Medical), clearance number M200946. Results: Most participants were between the ages of 25-35 (170, 47.8%), working more than 20 years (101, 28.4%), mostly in orthopaedic manipulative therapy (137, 38%) and in outpatient practice (199, 55.9%). Most participants had positive attitudes regarding the perceived ease of use and perceived usefulness (Valdez et al., 2009). Only 18.3% of participants used telerehabilitation in their clinical settings and less than half of the participants state that they would be willing to use telerehabilitation in their clinical setting. Only 37.3% of participants thought that the South African population would be receptive to telerehabilitation. Most participants thought that there is not enough knowledge (308, 86.5%) and awareness (262, 73.6%) about telerehabilitation but do have the capacity and resources to conduct telerehabilitation sessions in their clinical settings (227, 63.8%). Participants in OMT and outpatient practice had a more favourable attitude toward telerehabilitation. No significant effects of age were found. Conclusion: Physiotherapists show positive attitudes on the use of telerehabilitation but are not willing to do it in their clinical settings due to numerous barriers that affect the feasibility thereof. This study is one of the first to investigate the attitudes of physiotherapists on the use of telerehabilitation, however, further studies need to be conducted to examine the effectiveness of telerehabilitation amongst physiotherapists in South Africa. It is the hope that the awareness, knowledge, and skill to conduct telerehabilitation increases among physiotherapists in South Africa so that use of telerehabilitation can become common practice.Item 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, NeelaveniBackground: 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)Item Mode of delivery, analgesic, and neuromusculoskeletal profile of women developing new onset lower back pain postpartum(University of the Witwatersrand, Johannesburg, 2024) Steyn, JorethaThe 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.Item Novel Design and Analysis of an Oral Cannabidiol (Cbd) Therapeutic Delivery System for Pain Management(University of the Witwatersrand, Johannesburg, 2023-11) Khan-Flear, Faryal; Adeyemi, Samson A.; Kondiah, Pierre P. D.; Choonara, Yahya E.Cannabidiol (CBD) is a non-psychoactive cannabinoid used for its antinociceptive, analgesic and anti-inflammatory properties in chronic pain. The endocannabinoid system (ECS) influences CBD: receptor binding to generate or regulate antinociceptive responses, producing centrally acting analgesia predominantly through Cannabinoid receptor 1 (CB1) abundant in the brain and spinal cord. In contrast, Cannabinoid receptor 2 (CB2) modulates inflammatory responses in immune system cells and tissues. Most oral medications can have inefficient absorption ability and insufficient therapeutic bioavailability due to the solubility of active ingredients and dosage form dissolution. Although the high lipophilicity of CBD enables it to cross the blood-brain barrier (BBB), which prevents the entry of most systematically administered drugs, the oil-soluble CBD is poorly soluble in water, resulting in erratic, incomplete absorption and poor drug bioavailability, preventing therapeutic doses from reaching specific receptors and regions in the brain. Directly ingested CBD also undergoes hepatic and intestinal metabolism, further contributing to therapeutic insufficiencies. Lipid-Based Drug Delivery Systems (LBDDS) can circumvent the drug's hysicochemical properties and the body's protective biological barriers to enhance drug-receptor interaction and elicit a biological response. Lipid combinations in self-emulsifying lipid formulations (SELF) create liposome nanocarriers that entrap and release CBD, providing a non-invasive, transitory, regionally selective delivery method. Nanoliposomes restrict therapeutic delivery to targeted areas, minimizing systemic toxicity and improving drug bioavailability. Manipulating the physical, chemical, and mechanical aspects of nano-liposomes and the material properties of their constituents concerning human anatomy and physiology can help or hinder therapeutic efficiency, drug safety, and delivery. Most therapeutic nanoliposome designs fall within 50–100 nm, facilitating passive transport across the BBB enabling drug receptor binding at brain and spinal cord receptor sites. Modulator uptake and interactions with host cells, enhanced uptake by target cells, and limits accumulation in specific tissues. Nanoliposomes smaller than 100 nm also extend blood circulation by evading renal, hepatic, and immunogenic sequestration and clearance by the mononuclear phagocyte system (MPS), the reticuloendothelial system (RES), opsonization, modulator uptake and interactions with host cells, limited accumulation in specific tissues, low uptake by target cells. This experiment used established system predictors such as HLB and LogP values, Poulton's Lipid Classification System (LCS), Biopharmaceutics Classification System (BCS), Lipinski's Rule of 5 (Ro5), FBDD Rule of 3 (Ro3), Biopharmaceutics Drug Disposition Classification System (BDDCS) to evaluate the critical quality attributes of two optimized formulations able to deliver CBD to the brain and spinal cord. Both formulations consisted of a phospholipid (soy lecithin), unmodified vegetable oils (coconut, olive/castor oil), surfactants (Span 80 and Tween 20), and a cosolvent (ethyl acetate) in the same ratios with the same ingredients, except that the olive oil in one formulation replaced castor oil in the other. These formulations molecularly dispersed CBD in the polymeric matrix of an unstable amorphous solid dispersion (ASD), improving drug solubility and bioavailability compared to crystalline forms. Thermodynamically unstable ASD must be assessed for quality, stability, and resilience to design helpful dosage forms. Both optimized validation batches successfully encapsulated CBD in liposomes in the eutectic ASD mixtures, as reflected in Fourier transform infrared spectroscopy (FTIR) spectrograms and the Differential scanning calorimetry (DSC). The olive oil-containing formulation produced self-micro-emulsifying drug delivery system (SMEDDS). At the same time, the castor oil preparation formed a self-nano-emulsifying drug delivery system (SNEDDS), accounting for the differences in particle size, size distribution, zeta potential, rheology, morphology, drug release and cell culture analysis. The differences arose due to the oils' unique fatty acid composition and chemistry. Drug release test results of each formulation loaded in hydroxypropyl methylcellulose (HPMC) capsules showed good timing for capsule dissolution and a burst release preceding sustained release over 48 hours. Drug release test results established cell viability in culture studies. The positive cell proliferation indicated that the CBD concentrations released by both formulations were non-toxic to mouse embryonic fibroblasts (NIH/3T3) and human embryonic kidney epithelial cell (HEK 293) cultures. Although both formulations yielded favourable results, the analysis indicated that the castor oil formulation was more robust and, therefore, suitable as a nanocarrier for CBD.Item 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, SueCurrently, 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 environmentItem Record review of patients with brain abscess and empyema.(University of the Witwatersrand, Johannesburg, 2010-01-22T10:28:25Z) Schwenke, Katherine LindaStudies of patients presenting with brain abscess (BA) and Empyema are not routinely focused on occupational therapy (OT). There is a paucity of literature on deficits other than hemiplegia. Aims of this study were to determine the relationship between BA, Empyema, motor and other deficits and whether an OT intervention protocol is needed. Record review was used to establish clinical presentation trends. Hemiplegia was the most common motor deficit and the majority scored below the norm on the Beery- Buktenika Developmental Test of Visual Motor Integration (VMI). Patients with Brain Abscess generally had more significant deficits than those with Empyema for both motor and process deficits. Part B followed up a small sample (n=8) which indicated clinical improvement on the VMI test with the score on the supplemental test of motor coordination remaining a concern. Occupational Therapy is recommended to address these issues based on the Occupational Therapy Practice Framework-II.Item Running-related injuries and risk factors among runners in Soweto township clubs, Johannesburg(University of the Witwatersrand, Johannesburg, 2024) Masilana, Masocha Vusi; Kunene, SiyabongaThe 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.Item Targeted nanosystems for tuberculosis pericarditis interventions(University of the Witwatersrand, Johannesburg, 2024) Ayodele, Simisola Ayobami; Kumar, Pradeep; Choonara, Yahya EssopTuberculosis (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