Faculty of Health Sciences (ETDs)
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Item Design and development of a bioactive-loaded polymer-engineered neural device for potential application in reducing neurological deficits after spinal cord injuries and neuro-regeneration(University of the Witwatersrand, Johannesburg, 2017) Kumar, Pradeep; Choonara, Yahya Essop; Modi, Girish; Naidoo, Dinesh; Pillay, VinessTraumatic Spinal Cord Injuries (SCI), due to their devastating nature, present several interventional challenges (extensive inflammation, axonal tethering, scar formation, neuronal degeneration and functional loss) that need to be addressed before even a slight neuronal recovery can be achieved. Recent post-TSCI investigational approaches include support strategies capable of providing scaffold architecture to allow axonal growth and conformal repair. This research provided detailed insight towards the development and fabrication of six specialized Polymer-Engineered Neural Devices (PENDs): 1) poly(lactic-co-glycolic acid)-gliadin (PLGA-GLDN) nanofibrous mats, 2) polyacrylamidated chitosan (PAAm-g-HT) scaffold, 3) functionalized chitosan methoxypolyethylene glycol (CHT-mPEG) cryosponges, 4) polyacrylonitrile-elastin-collagen (PANi-EC) neurosponge, 5) methylcellulose-alginate-polyethylene glycol (MAP) thermogel, and 6) chitosan-luronic F127-β glycerophosphate (CHT-PF127-βGP) composite thermogel for potential restriction, repair, regeneration, restoration and reorganization post-SCI. The latest trends in biomaterials-based SCI intervention were reviewed, discussed and analyzed in detail throughout the thesis. The research also involved an in silico analytico mathematical interpretation of multi(biomed)material assemblies wherein quantification of energy surfaces and molecular attributes via atomistic, dynamic, and docking simulations was carried out. The in silico experimentation additionally confirmed the potential of curcumin as a bioactive of choice for SCI intervention. Curcumin and dexamethasone were incorporated into the compact scaffolds and the bioactive release was determined over a period extending up to 60 days. The PLGA-GLDN nanofibrous mats demonstrated the formation of a compatible blend among the component polymers at equal weight ratios (PG55) as confirmed by quantitative physicochemical characterizations. Image processing analysis (DiameterJ plug-in of ImageJ) was performed on the SEM images of nanofibers to quantify the size, porosity, and orientation of the samples. Nanofibers within the size range of 10nm and 250nm were obtained in case of compatible blend and the nano stack was used for in vivo implantation post-SCI. Polyacrylamidated chitosan (PAAm-g-CHT) was synthesized via a unique persulfate-mediated polymer slicing and complexation as determined by static lattice atomistic simulations. The graft copolymer so obtained was fabricated into an anisotropic neurodurable scaffold. The CHT/mPEG cryosponges showed unique morphological features such as fringe thread-like structures (CHT alone); hemispherical, pebble-like structures (CHT-mPEG); curved quartz crystal-like or crystal-flower-like structures (CHT-mPEG-CHO); and grouped, congealed, steep-sided canyon-like structures (CHT-mPEG COOH). A novel image processing protocol involving DiameterJ and ND plugins of ImageJ software was employed for analyses of the SEM micrographs in terms of % porosity, pore wall thickness and % xiiehaviorxii of the porous scaffolds. The PANi-EC interpenetrating polymer network neurosponges were synthesized employing free radical polymerization under acidic conditions wherein first-in-the-world spinomimetic scaffolds were obtained. The unique feature of the PANi-EC neurosponge was the formation of a fibrous neurotunnel architecture mimicking the native spinal cord. The physicochemical characterization revealed that the secondary structure of the peptide molecules (elastin and collagen) rearranged in the presence of PANi to their native extracellular matrix (ECM) form confirming the self-assembling nature of the polymer-peptide architecture. Furthermore, the PANi-EC neurosponge provided a perfect balance of matrix resilience and matrix hardness similar to the native collagen-elastin complex in vivo. Two very interesting tri-component thermogels were reported here viz. a simple blend thermogel comprising methylcellulose, sodium alginate and poly(ethylene glycol) and a complex thermogel incorporating chitosan, Pluronic F127 and β-glycerophosphate. Both the thermogels solidified at physiological temperature confirming their applicability in vivo. The outstanding feature of MAP thermogels was the formation of hydrogen bonded O-H…C=O which only formed in the tripolymeric blend while the bipolymeric blends showing no such interaction. We proposed that the MAP thermogel self-assembled into a repeating network structure represented by “PEG400-ALG-hydrophillicMChydrophobic}-{hydrophobicMC-hydrophilic}-ALG-PEG400” and the physical “compression” might have led to the formation of hydrogen bonded O-H…C=O among MC/alginate or PEG/alginate in the presence of PEG or MC, respectively. In case of the complex CHT/PF127/βGP thermogel, a unique triphasic gel-sol-gel transition xiiehavior was observed with the thermogel forming a gel-phase at lower temperatures (T<20°C), a sol-phase at intermediate temperatures (20°C35°C). The MTT proliferation studies indicated that all polymer engineered neural devices (PANi-alone matrix) were capable of efficiently supporting the growth of PC12 cells compared to the control over a period of 72 hours. The fundamental objective of this thesis was to test the applicability and capability of various biomaterial composites towards the repair and regeneration of neuronal tissue after traumatic spinal cord injury. Although drug-loaded scaffolds were also developed, only drug-free scaffolds (PLGA-Gliadin 5:5 electrospun nanofibers; PANi-Elastin-Collagen neurosponge; and Chitosan/Pluronic F127/β-glycerophosphate thermogel) were tested in vivo for the proof-of-concept. The 21-point scale BBB locomotor rating analysis demonstrated that PEND I (14), PEND II (19) and PEND III (18) provided significant motor recovery as compared to the lesion-control (5) group 28 days post-SCI and –implantation. The immunohistochemistry confirmed that reparative changes were accompanied by marked upregulation of iNOS, a notable influx of ED1-positive chronic inflammatory cells, the appearance of multinucleate cells characteristic of presumptive regenerative neuroblasts and near-complete loss of GFAP and NF-200 protein/structural integrity. Almost complete functional and neurostructural recovery was observed with post-SCI implantation of PEND II and III. In conclusion, the composite scaffolds tested in this research demonstrated immense potential in improving the neurological, neurochemical, and behavioral outcome after implantation post-SCI.Item Comparing health inequalities in maternal health: An analysis of the South African Demographic and Health Surveys (SADHS) 1998 and 2016(University of the Witwatersrand, Johannesburg, 2023-09) Holden, Celeste Claire; Blaauw, DuaneBackground: Inadequate access to maternal health services (MHS) is directly linked to maternal and neonatal mortality and morbidity. South Africa (SA) is known to be an unequal society. Researching and documenting the utilisation and access to MHS can assist in the appropriate redirection of services to ensure equitable service delivery. The study identifies differences in MHS access between ethnicity groups, residence, province, maternal education level and household wealth quintile. The study quantifies the inequalities in access to MHS in SA in 1998 and 2016, and then evaluates the change in inequalities between the two periods. Methods: Data was analysed from the 1998 and 2016 South African Demographic and Health Surveys. First. the study identifies differences in MHS access between ethnic groups, residence, province, maternal education level and household wealth quintile using regression analyses. Then, the inequalities related to access of MHS in 1998 and 2016 are calculated using the relative (RII) and slope (SII) index of inequality and the concentration index (CI). Lastly, the inequalities between 1998 and 2016 were compared using generalised linear models, indicating whether inequalities increased, decreased, or remained the same. All analyses were done in Stata and adjusted for the multistage-stratified sampling of the surveys. Results: Utilisation of MHS in SA varies between different groups based on ethnicity, residence, province, mothers’ education level, and wealth quintile. In 1998 and 2016, Black/African women have the least utilisation of all MHS. A clear pattern is seen where women with higher education and high wealth quintile, have increased MHS utilisation. In most cases, the inequalities narrowed between 1998 and 2016 for all MHS. However, inequalities are still present in 2016 for many MHS. For example, using simple inequality measures, the largest inequalities in 2016 are seen between women of different ethnicities accessing four or more antenatal visits (ANC4), where there is a 11.1 percentage point difference between the highest group (White & Indian/Asian) and the lowest group (Black/African). For complex inequality measures, there are still significant relative and absolute inequalities in antenatal visits in 2016 for maternal education (RII: 1.25; SII: 1.14) and household wealth quintile (RII: 1.23; SII: 1.11). Conclusions: Between 1998 and 2016, population-level utilisation to MHS increased in all MHS and the majority of within group inequalities narrowed over time. However, inequalities still exist in all maternal health outcomes. SA has implemented multiple programmes and policies to address inequalities in MHS and decrease maternal mortality and morbidity. However, these need to be continuously monitored and evaluated based on the latest data to ensure that efforts are going towards addressing the specific groups where inequalities are still present.Item Experiences of healthcare workers using the AwezaMed translation application in antenatal settings(University of the Witwatersrand, Johannesburg, 2023-06) Cason, Caroline Marian; Slemming, Wiedaad; Wilken, IlanaIntroduction: Language barriers impede quality health care service in South Africa. Trained interpreters could alleviate this problem, but they are not employed in public or private health settings. Health care workers rely on informal interpreters, who do not necessarily provide an adequate service, and may be resentful of this extra task. AwezaMed is a smart application developed by the Council for Scientific and Industrial Research (CSIR) with content developed for maternal health settings. The aim of this study was to assess usability and user experience relating to AwezaMed. Methods: A user experience study was conducted using mixed methods. The systems usability scale (SUS) was employed, surveying 12 users, to generate a quantitative score, representing the overall usability of the system. Interviews were conducted with 14 users and analysed thematically to identify themes of usability and user experience, and recognise factors which contribute to use of the application. Results: The application (app) achieved a total score of 66.25, rating it between ‘OK/Fair’ and ‘Good’. Understandability, operability, attractiveness, and trust were important usability themes. Users also reported using the app as an aid to language learning. Factors which influenced the use of the app included previous experience with mHealth, experiencing a language barrier in health settings, and unavailability of, or problems with interpreters. Discussion: While the app was received positively, it did not meet users’ expectations, as two-way communication could not be achieved. Due to the often-strained relationship between healthcare workers and informal interpreters, there remains a demand for a usable, trustworthy mHealth solution. A framework is proposed, based on these findings, to evaluate mHealth translation applications in South Africa in the future.Item Reporting Silica Dust Exposure Measurements in South African Gold and Coal Mines: 2005 to 2016(University of the Witwatersrand, Johannesburg, 2023-10) Mongoma, Brian Tshepo; Nelson, Gill; Brouwer, DerkBackground: Arising from the Mine Health and Safety Act 29 of 1996 (MHSA), one of the measures to protect mine workers is monitoring exposure to airborne pollutants. Mines are statutorily required to report airborne pollutant concentrations to the Department of Mineral Resources and Energy (DMRE) on a regular basis. Based on the DMRE's 2013 report, it was determined that 76% of workers were exposed to airborne pollutants at concentrations less than 10% of their respective occupational exposure limits (OELs). Using the same exposure data from the DMRE, the Chamber of Mines of South Africa reported a 14% improvement in the exposure to the airborne pollutants from 2005 to 2013. However, these reported reduced exposures to airborne pollutants are based on the summation of all airborne pollutant exposures by the DMRE. The annual reports refer to the percentage of employees exposed to the combined airborne pollutants, rather than to specific pollutants, such as silica dust – a hazard that is high on the occupational health agenda of the mining industry. From these reports, broad (and perhaps incorrect) conclusions are reached with regard to trends in silica dust and other exposures. The limitations of the SAMI include inaccurate data, self-regulation, incomplete employment and exposure records, and historical biases, which hinder its ability to effectively handle occupational health risks. This emphasizes the immediate need for clear and consistent regulations, accurate data collection, and impartial research approaches to protect the health of mine workers. Objectives: The objectives of this study were to describe trends in combined airborne pollutant and silica dust concentrations from 2005 to 2016, and to evaluate the DMRE Mandatory Code of Practice (MCoP) and the EN 689 methods (for testing exposure levels in the workplace against the OEL of 0.1 mg/m3) as published by the European Committee for Standardization (CEN), using reported silica dust concentrations from 2015 and 2016. Methods: This was a cross-sectional study in which secondary airborne pollutants exposure data, reported to the DMRE by coal and gold mining members of the Minerals Council, were analysed. The 282 870 data points were pooled together to describe trends in airborne pollutant exposures as they comprised 69 airborne pollutants reported by different mines with various mining methods, activities, and occupations. The exposure data was categorized into coal and gold mines, and further into four three-yearly periods (i.e. period 1: 2005-2007, period 2: 2008-2010, period 3: 2011-2013, and period 4: 2014-2016). This was conducted in order to have a consistent metric to allow for uniform assessment across different pollutants with varying OELs. Dividing the exposure concentration by its OEL provided a ratio, similarly to the way that an Air Quality Index is calculated. As a result, the data was normalized by dividing each pollutant exposure concentration by its occupational exposure limit (OEL) to obtain a ratio, termed Q. The arithmetic mean, standard deviation, geometric mean, and geometric standard deviation of the Qs were calculated for each of the three groups i.e. coal and gold mines combined, b) coal mines, and c) gold mines, for each period. Jeffreys’s Amazing Statistics Program was used to analyse the Qs and silica dust concentrations. The Kruskal–Wallis test was used to identify statistically significant differences among the four time periods for each commodity group. Additionally, Scheffe’s post-hoc test in JASP was conducted for further analysis and comparison of differences across all observed periods. Two methods, namely the EN 689 and the method required by the DMRE MCoP, were used to assess compliance. EXPOSTATS Tool 1 was used to calculate the arithmetic mean (AM), median, standard deviation (SD), geometric mean (GM), geometric standard deviation (GSD), and 90th and 95th percentiles of the exposure data derived from EN 689. Microsoft Excel was used to calculate the 90th and 95th percentiles of the exposure data based on MCoP method. A total of 127 014 silica dust data points from 2005 to 2016 out of the 282 870 were utilized to describe silica dust exposure trends, and 44 990 data points from the 127 014 were used to assess compliance for the years 2015 and 2016. Results: A total of 282 870 personal airborne pollutant concentrations from 2005 to 2016, obtained from DMRE, were included the analysis. Analysis of the pooled airborne pollutant exposure concentrations indicated that there was a high variability (data points were far apart and also far from the GM) as the GSDs ranged from 6.37 to 7.53, 7.8 to 8.43, and 5.7 to 6.16 for the coal and gold mines combined, coal mines alone, and gold mines alone, respectively. The variabilities of the silica dust concentrations were less than that of the pooled airborne pollutant data. The GSDs of the silica dust concentrations were < 3.5 for all three groups compared to the GSDs calculated from the pooled airborne pollutants concentrations, where the lowest GSD was 5.7. The trends in the pooled airborne pollutant exposure concentrations over the 12-year period, for all three groups, showed that there was a reduction in reported exposures to combined airborne pollutants. The AMs of the ratios (Q) indicated that the reduction in exposures for coal and gold mines combined, gold mining alone and coal mining alone, were 57%, 55% and 26%, respectively. The corresponding GMs of the ratios (Q) for gold mining alone, coal and gold mines combined, and coal mining alone, reduced by 64%, 45% and 15%, respectively, from 2005 to 2016. The distribution of the airborne pollutant data was skewed, which affected AM more than GM, and resulted in differences between the two measures. This was evident in the gold mining data, where the AM decreased by 55% but the GM decreased by 64%. Data for the period 2005-2007 had the highest AM (1.54) and standard deviation (2.75), suggesting that there were outliers. In this period, ratios (Q) ranged from 0.003 to 7.7, impacting the AM and creating a gap between median and AM values. From 2008 to 2010, the AM (1.26) and SD (2.04) decreased, showing reduced variability. A similar trend was observed from 2011 to 2013, with increased numbers of observations and further reduced variability. In 2014-2016, the AM decreased to 0.67 and SD to 1, indicating stability. The GMs for the coal and gold mines combined, coal mines alone and gold mines alone ranged from 0.17 to 0.31, from 0.22 to 0.28, and from 0.16 to 0.45, respectively. The trends in reported silica dust concentrations in all three groups showed a reduction over the 12-year period. The AMs indicated that the reductions for coal and gold mines combined, gold mining alone and coal mining alone, were 61%, 38% and 34%, respectively. The GMs of the silica dust concentrations indicated that the reductions in exposures for coal and gold mines combined, coal mining alone, and gold mining alone, were 54%, 35% and 31%, respectively. The AMs of the silica dust concentrations for coal and gold mines combined ranged from 0.17 to 0.44 mg/m3, while the coal mines ranged from 0.67 to 1.02 mg/m3 from 2005 to 2016. For gold mines, the AMs ranged from 0.13 to 0.23 mg/m3. Similarly, the GMs of the silica dust concentrations for the coal and gold mines combined ranged from 0.11 to 0.24 mg/m3, whereas coal mines ranged from 0.41 to 0.63 mg/m3, and gold mines ranged from 0.09 to 0.13 mg/m3. The 90th percentiles for the silica dust concentrations almost correlated with the AMs as they reduced by 67%, 40% and 34% for coal and gold mining combined, gold mining alone, and coal mining alone, respectively. The 90th percentiles for silica dust concentrations for the coal and gold mines ranged from 1.64 to 2.48 mg/m3, and 0.29 to 0.51 mg/m3, respectively. Although the trends indicated a reduction in exposure to silica dust concentrations, the AM, GM, 90th and 95th percentiles exceeded the OEL of 0.1 mg/m3 for the entire study period for the three groups, except for the gold mines alone in 2016. In that year, the GM was 0.09 mg/m3 (rounded to 0.1 mg/m3). For coal mining only, the 90th percentiles ranged from 1.64 to 2.48 mg/m3, whereas the 95th percentiles ranged from 2.16 to 3.16 mg/m3. For gold mining only, the 90th percentiles ranged from 0.29 to 0.51 mg/m3, and the 95th percentiles ranged from 0.35 - 0.63 mg/m3. A total of 44 990 silica dust concentrations were used from 2015 to 2016 to compare the 95th percentiles according to EN 689, and the 90th percentiles according to the MCoP. The DMRE MCoP method was shown to underestimate the exceedance of the occupational exposure limit by 5-26%, when compared with the EN 689 method. Conclusion: Despite the variabilities and challenges associated with pooling the airborne pollutants concentrations in the coal and gold mining industries, exposures to the airborne pollutants in the three commodity groups decreased from 2005 to 2016. However, reporting employee exposure as pooled airborne pollutants concentrations is flawed and obscures exposures to individual pollutants such as silica dust. The three commodity groups showed a decrease in silica dust exposure measurements from 2005 to 2016. However, there was still overexposure to silica dust in the three groups (greater than the OEL of 0.1 mg/m3). Inhalation of particles containing silica was higher in the coal than the gold mines, which is contradictory to what is known about the silica content of the ores in which the two commodities are found. The DMRE MCoP approach to compliance with silica dust levels underestimated the exceedance of the OEL in comparison to the EN 689’s approach. The current DMRE reporting methodology, i.e. the pooling of all data, does not allow accurate reporting of silica dust exposures and as a result, it does not provide direction or support for carrying out measures to decrease exposure to silica dust. The MCoP method for compliance testing revealed higher 90th-percentiles for coal mining compared to the 90th-percentile estimated for the population (EN 689). For gold mining it was the opposite. The EN 689 method is a more precise means of estimating OEL compliance, which is crucial for managing silica dust and specific pollutant health hazards and should be used in favour of the method in the MCoP.Item A retrospective study on the outcomes of peripartum hysterectomies for puerperal sepsis at Chris Hani Baragwanath Academic Hospital(University of the Witwatersrand, Johannesburg, 2024) Olusola, Esther; Naidoo, PoovangelaBackground: Puerperal sepsis is a significant cause of maternal morbidity and mortality, especially in developing countries. Hysterectomy is often performed as a measure of source control for severe uterine infections when conservative treatment fails. The aim of this retrospective study was to examine the outcomes of peripartum hysterectomies performed for puerperal sepsis at Chris Hani Baragwanath Academic Hospital, Johannesburg, South Africa. Methods: A retrospective cross-sectional study was conducted between 1 January and 31 December 2019, on all women who underwent hysterectomies for puerperal sepsis. Data pertaining to demographics, surgical characteristics, microbiological cultures, organ dysfunction scores, and histopathological findings, were extracted from medical records. Women with miscarriages or pregnancies less than 24 weeks’ gestation were excluded. Statistical analysis included descriptive methods and comparative tests using Stata 15.0 software. Organ dysfunction scores were calculated using MODS, SOFA, and qSOFA systems. Ethical approval was obtained prior to conduction of the study. Results: During the study period, 33 hysterectomies were performed for puerperal sepsis, representing 0.17% of the 18,458 deliveries at the hospital. The median age of women was 28 years of age with a median gestational age at delivery of 38 weeks. The majority (88%) underwent total abdominal hysterectomies, while 12% had subtotal hysterectomies. Eighty eight percent of women underwent caesarean section for a fetal distress. The most common organisms cultured in intra-abdominal fluid were Acinetobacter baumannii (26%), Escherichia coli (19%), Klebsiella species (14%) and Enterococcus faecalis (14%). A. baumannii was the predominant pathogen in all four culture mediums. The most common antibiotics used in this hospital for treatment were resistant against most organisms. Women with higher MODS and SOFA scores predominantly cultured resistant organisms. A. baumannii was strongly associated with worse outcomes. Two women (6%) died due to complications of ongoing sepsis. Histological examination revealed that surgeons often underestimated the extent of necrosis (30%) and presence of pus (44%), highlighting the importance of histopathological evaluation for accurate diagnosis and management. Conclusion: This study highlights the rising antibiotic resistance which complicates treatment and emphasises the need for revision of antibiotic stewardship in puerperal sepsis management. Women with higher MODS and SOFA scores predominantly cultured resistant organisms. Further research is required to explore improving surgical recognition of uterine sepsis and whether a total abdominal hysterectomy is actually superior to a subtotal hysterectomy in women with puerperal sepsis.Item The effect of two modalities of sleep disruption on immunity in healthy young female participants(University of the Witwatersrand, Johannesburg, 2023-07) Ajlan, Zuha; Scheuermaier, Karine; Iacovides, StellaStudies have shown that sleep deprivation leads to an inappropriate immune response by elevating pro-inflammatory markers, including interleukin (IL-)1, IL-6, and tumour necrosis factor (TNF-)α. This inappropriate immune activation increases the risk of developing autoimmune disorders. Despite women representing 80% of patients with autoimmune disorders and having a greater prevalence of poor sleep quality and sleep disorders, most experimental human studies investigating sleep and immunity focused on men. Therefore, this study assessed the effect of sleep fragmentation vs sleep restriction on sleep parameters. I then compared the immune response after the two types of sleep disruptions relative to a normal sleep episode and I investigated the association between sleep architecture and immune markers in healthy young women in the follicular phase of their menstrual cycle. Fourteen healthy females underwent a randomised-crossover controlled study consisting of one adaptation night and three randomised, non-consecutive sleep conditions, namely: baseline night (BN, uninterrupted 8 hours of sleep); restriction night (RN, sleep was limited to the first 4 hours of their habitual sleep episode); fragmentation night (FN, eight randomised forced awakenings through an 8-hour sleep opportunity night). Polysomnographic (PSG) sleep recordings were obtained for each condition, and plasma was collected 2.5 hours after their habitual waketime following each condition. A multiplex Luminex assay was used to measure the concentration of nine cytokines. I compared PSG-extracted sleep variables between the three experimental nights. I ran mixed models analyses testing cytokine levels in each sleep condition (RN vs. FN vs. BN) in unadjusted analyses and then adjusting for order of the condition (first vs. second vs. third experimental night), day of follicular phase of the menstrual cycle and age. I also used an unadjusted mixed model analysis to test the association between cytokine levels and each sleep variable. Total sleep time, non-rapid eye movement (NREM) and rapid eye movement (REM) were reduced in FN and RN but were lowest during RN (p<0.001). I found an effect of sleep condition on IL-8 (F = 3.40, P = 0.05) with IL-8 being lower in RN vs FN or BN. There was no effect of condition on the other cytokines in unadjusted or adjusted analyses. Lower wake after sleep onset (WASO) and higher NREM were associated with higher IL-8 concentration regardless of the sleep condition. Lower stage 2 (N2) (F = 6.28, β = -0.001, P = 0.02) and higher stage 3 (N3) (F = 7.01, β = 0.004, P = 0.01) was associated with a higher TNF-α regardless of the sleep condition. In conclusion, the study shows that acute sleep disruption alters sleep architecture and leads to an inappropriate immune activity in young healthy women. Future studies should try and investigate chronic sleep fragmentation vs chronic sleep restriction on the immune system.Item Patterns of HIV Resistance in Children Attending an Antiretroviral Clinic in Soweto, South Africa: A Case-Control Study(University of the Witwatersrand, Johannesburg, 2023) Vilakazi, Zinhle; Moore, David Paul; Sipambo, Nosisa; Steegen, KimBackground: Exposure to suboptimal serum levels of antiretrovirals (ARVs) places resistance pressure on circulating human immunodeficiency virus (HIV), with consequent emergence of resistance. HIV resistance leads to treatment failure and adverse outcomes. We explored factors associated with the emergence of ARV resistance in children living with HIV (CLWH) attending a treatment clinic in Soweto. Methods: We reviewed the clinical and laboratory characteristics, and factors associated with ARV resistance in children aged 0 to 15 years of age that were treated at the clinic from 01 January 2011 through 31 December 2020. The Stanford HIV drug resistance database was used to identify HIV drug resistance mutations and generate resistance profiles. Characteristics of children that underwent drug resistance testing (DRT) were compared to those of children who remained virologically suppressed on fist-line ARVs. Results: During the study period, 7,029 children attended the clinic of which 425 (6.0%) underwent DRT (cases) and 953 (13.6%) remained suppressed on first-line ARVs (controls). The resistance dataset included 431 resistance tests that were done in 425 children and adolescents that were eligible for the study. Non-nucleoside reverse transcriptase inhibitor (NNRTI) mutations accounted for 50.8% of all mutations, followed by nucleoside reverse transcriptase inhibitor (NRTI) mutations (44.5%) and protease inhibitor (PI) mutations (4.6%). Cases were significantly older at ARV initiation (81.6 vs 45.2 months), had a higher prevalence of ever being diagnosed with tuberculosis (33.2% vs 27.4%), ever being orphaned (57.6% vs 50.6%) and ever experiencing severe acute malnutrition (SAM) (19.8% vs 11.7%). In all modelling approaches, SAM was consistently associated with ARV resistance adjusted odds ratios (aOR) ranging from 3.548 (95% confidence interval (CI) 1.979-6.359) to 6.383 (95% CI, 3.811-10.690)). Increasing baseline CD4 percentage was associated with significantly lower adjusted odds of case-status aOR ranging from 0.971 (95% CI, 0.953-0.989) to 0.951 (95% CI, 0.931-0.972)). Seventeen (5.6%) cases died, compared to two (0.3%) controls; P<0.001. Conclusions: Tenuous nutritional status was consistently and significantly associated with the requirement for DRT in this cohort of children and adolescents. Conversely, higher baseline CD4 percentage was associated with control status. Early ARV initiation, to preserve immunological status, and nutritional support throughout the course of clinic attendance may limit the emergence of drug resistance in CLWH.Item Voiding cystourethrography in the renal pre-transplantation workup: an essential investigation?(University of the Witwatersrand, Johannesburg, 2022-10) Sofianos, Zelia; Rajkumar, Leisha; Lucas, SusanINTRODUCTION: Due to resource constraints in the South African public healthcare sector, patients with End-Stage Renal Disease (ESRD) are eligible for renal replacement therapy only if they are also found to be eligible for renal transplant. AIM: The aim of this study is to document Voiding Cystourethrogram (VCUG) findings in potential renal transplant candidates to assess the contribution of the VCUG as a standard investigation in the renal transplant workup. METHODS: Of the patients who underwent VCUG in Klerksdorp/Tshepong Hospital Complex (North West province, South Africa) from 1 January 2019 to 31 March 2020, 85 patients were included in the study and their VCUG findings retrospectively analysed. RESULTS: The mean age was 40.0 years (range 21-62 years), with males constituting 57.7% of patients and females 42.3%. Lower urinary tract abnormalities were identified in 24.7% of patients, some of whom had more than one abnormality. Of the total abnormalities, VUR (vesicoureteral reflux) accounted for 15.3%, bladder diverticula for 5.9%, urethral strictures for 3.5% and a significant post-void residual volume for 4.7%. No comorbidities were found to have a statistically significant association with the presence of VCUG abnormalities. CONCLUSIONS: To ensure that patients with End-Stage Renal Disease are adequately prepared for renal dialysis and potential renal transplant, and that their comorbidities and lower urinary tract are optimised should abnormalities be identified on VCUG, the VCUG remains an essential investigation in the renal transplant workup.Item Emergency Department Turnover Intention: Are Job Satisfaction and Burnout Really the Main Culprits?(University of the Witwatersrand, Johannesburg, 2022-11) Jonker, Yvonne Denise; Motara, Feroza; Moolla, MuhammedBackground: Patient presentations to emergency departments (ED) keep increasing. High staff turnover is detrimental to the healthcare worker (HCW), the organisation and the patient. While high levels of burnout (BO) and low levels of job satisfaction (JS) lead to a higher intention to leave (ItL), there are other factors affecting the ItL that need to be evaluated. Objective: To determine the levels of BO, JS and ItL, including when, where and why HCWs want to leave in order to find ways to reduce staff turnover. Methods: This was a prospective observational cross-sectional study conducted in two tertiary-level EDs in Johannesburg, South Africa namely Chris Hani Baragwanath Academic Hospital (CHBAH) and Charlotte Maxeke Johannesburg Academic Hospital (CMJAH). Doctors and nurses were invited to complete self-administered questionnaires between 24 November 2020 and 24 March 2021. After analysis the results for doctors and nurses and the two units were compared in order to bring understanding to the different facets affecting staff turnover. Results: A total of 78 respondents (66% of doctors and 58% of nurses) completed questionnaires and were included for analysis. According to the Copenhagen Burnout Inventory 79% of CHBAH doctors, 62% of CHBAH nurses, 79% of CMJAH doctors and 84% of CMJAH nurses suffered from severe personal burnout, while 68% of CHBAH doctors, 62% of CHBAH nurses, 95% of CMJAH doctors and 68% of CMJAH nurses suffered from severe work-related BO and 42% for CHBAH doctors, 24% of CHBAH nurses, 47% of CMJAH doctors and 32% of CMJAH nurses had severe patient-related burnout. Doctors had significantly higher patient-related burnout (p=0.012). JS was average for all staff but nurses were significantly less satisfied (p=0.003). While 42% of staff intended to leave within a year, of which half wanted to leave as soon as possible, a total of 73 % wanted to leave within 5 years. CMJAH staff had higher levels of BO, lower levels of JS and higher levels of ItL. Higher levels of BO and lower levels of JS increased the ItL. The main reasons for leaving were career-related. Conclusion: Burnout levels were higher than similar populations before and during the Covid-19 pandemic, while job satisfaction levels were average. Although burnout and job satisfaction affected intention to leave, the main reasons for wanting to leave were career-related indicating that even when work conditions and burnout could be addressed successfully, the turnover of staff in tertiary level EDs may remain high.Item Analysis of Orthopaedic Injuries in Polytrauma Patients at Charlotte Maxeke Johannesburg Academic Hospital(University of the Witwatersrand, Johannesburg, 2022) Laney, Wezley; Naicker, Dharshen; Milner, BrendaBackground: Traumatic injuries represent a significant burden globally, accounting for ten percent of the global burden of disease. In South Africa we commonly see patients who have sustained major trauma, often with multiple injuries. This significant burden of trauma necessitates the demand for rapid diagnostic assessment of injuries for appropriate therapeutic intervention. A whole body computed tomography (CT pan scan) allows for a rapid multisystem injury diagnosis of trauma patients. There is a scarcity of literature evaluating the extent of orthopaedic injuries in polytrauma patients. Study Aim: The aim of the study was to evaluate the local epidemiology of orthopaedic injuries in polytrauma patients who have undergone a CT pan scan. Methods: A retrospective, observational analysis, based at Charlotte Maxeke Johannesburg Academic Hospital, was done of polytrauma patients who underwent a CT pan scan, during a 2-year period from 01/01/2018 – 31/12/2019. A database was compiled by accessing the picture archiving and communication system for CT reports. The qualitative data was reported using frequencies and percentages. Categorical variables were analysed using the Chi-squared test (or Fisher’s exact test). Results: Over the two-year study period a total of 296 polytrauma patients had a reported CT pan scan performed. Of these, 85% were male and 15% were female with a median age of 33 years. The most common mechanism of injury was motor vehicle accidents (33.1%). The prevalence of orthopaedic injuries in polytrauma patients was 53.3%. A total of 1012 injuries were found. One hundred and ninety-six (196) spinal fractures were detected; a total of 137 pelvic/sacral fractures, 101 long bone fractures with 75% lower limbs and 25% were upper limb fractures. The most common non-orthopaedic injury sustained was a chest injury. The most common combination of orthopaedic and non-orthopaedic injuries identified in the study was a chest injury with an associated pelvic/sacral fracture secondary to a PVA. Interpersonal and intentional injuries were significantly associated with a higher risk of thoracic spine fractures (RR 1.8, CI 1.1-2.9). Road traffic accidents were significantly associated with a higher risk of scapular/clavicular fractures (RR 2.0, CI 1.2-3.5) and a higher risk of tibial/fibula fractures (RR 3.5, CI 1.2-10.3) Conclusion: The majority of polytrauma patients seen at CMJAH were young males, who sustained injuries during road traffic accidents. Fractures accounted for 94% of all orthopaedic injuries. The most common orthopaedic injury detected in our cohort, overall, was a spinal fracture, most commonly involving the cervical spine. A patient involved in a road traffic accident is 3.5 times more likely to sustain a tibia/fibular fracture as opposed to any other fracture. The most common non-orthopaedic injury sustained was a chest injury. Importantly, 1 in 4 of these patients sustained an associated cervical spine injury and 1 in 3 a pelvic injury, similarly with head injuries. The most common combination of injuries is a chest injury with an associated pelvic/sacral fracture secondary to a pedestrian vehicle accident. The findings highlight the significant burden of orthopaedic injuries in polytrauma patients. In addition, the findings of this study, highlight injury patterns that should be anticipated in polytrauma patients.