Clinical Medicine
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Item Human lymphocyte antigens.(1992) Hammond, Michael Graham.This thesis embodies much of my work done over the past 25 years. The impetus for these studies was the need to provide the best tissue typing available for organ transplantation and to overcome the problems of defining HLA antigens in different ethnic groups. These goals were achieved by extensive international collaboration and participation in the International Histocompatibility Workshops. The discovery that the HLA antigens are associated with many diseases led to an epidemic of investigations in which over 500 diseases have been studied. In retrospect, it is not surprising that auto-immune diseases such as diabetes and rheumatoid arthritis showed such marked associations with HLA antigens. The studies in Part II of this thesis were aimed at finding out if the HLA associations reported in Caucasian populations were also present in the Black and Indian populations. These research interests led to my being invited by the National Science Council of the Republic of China in Taiwan to be a Visiting Professor at the National Taiwan University in Taipei for the 1989 academic year. I investigated the association between HLA and naso-pharyngeal carcinoma in Chinese during that year. I wish to express my appreciation to Dr Peter Brain who inspired the early investigations and continued to encourage and support my research. I am grateful to all my co-authors and the many colleagues, clinicians and laboratory staff who have contributed to the various research programmes. Studies of the relationship of the HLA system to cancer, diabetes, arthritis and other diseases have been supported in part by grants from the National Cancer Association and the Medical Research Council of South Africa.Item Cardiovascular evaluation of hypertensive disorders of pregnancy by echocardiography.(2004) Desai, Dushyant K.; Moodley, Jagidesa.; Naidoo, Datshana Prakesh.Background: Preliminary observations suggest that aberrations in maternal central hemodynamics and uterine artery Doppler velocimetry reflect the severity of hypertensive disorders of pregnancy. In addition, the precise changes of cardiac output in normal pregnancy, particularly in the third trimester, have remained controversial. Aims and Objective: To measure concomitantly Doppler echocardiographic maternal central hemodynamics and uterine artery Doppler velocimetry and evaluate their association with adverse feto-neonatal outcome in hypertensive pregnant women. To evaluate cardiac output longitudinally in the latter half of pregnancy in normal healthy women. Design and Setting: Prospective study conducted at the Obstetric Unit, King Edward VIII Hospital, Durban, South Africa. Study sample: forty (40) pregnant hypertensives without any prior therapy and a further group of pre-eclamptic women (n=22) treated with stat dose sodium gardinal and alpha-methyldopa were studied. Results: i) A trend to a higher cardiac output was seen in the hypertensives compared to the normotensives. Hypertensive women were of larger stature; there was no difference in cardiac index. Fetal birthweight correlated poorly with cardiac index in pre-eclamptic women (r =0.21). A better correlation was seen with uterine artery resistance index (r = - 0.65) and systemic vascular resistance index (r = -0.49). Critical values for cardiac index and systemic vascular resistance index to predict poor adverse feto-neonatal outcome with good predictive values were not identified. ii) Pre-eclamptics treated with stat dose of sodium gardinal and/or methyldopa prior to echocardiography had a significantly lower systemic vascular resistance index and uterine artery resistance index compared to the untreated group. The lower systemic vascular resistance index in this treated cohort occurred from a combination of non-significant lower blood pressure and higher cardiac index. iii) Compared to normotensive women, untreated pre-eclamptics had a significantly lower heart rate (p< 0.001), a higher stroke index (p=0.018) and no difference in resultant cardiac index (p=0.452). iv) In gestational apoteinuric hypertensives presenting after 34 weeks gestation, maternal hemodynamics and uterine artery resistance index did not help define a higher risk group. v) In chronic hypertensives pregnancies, left ventricular hypertrophy correlated with severity of blood pressure. Higher risk chronic hypertensives were better selected by proteinuria than maternal central hemodynamics or uterine artery resistance index. vi) In normal pregnancy, maternal cardiac output peaked in early to mid third trimester and was maintained till term. Significant correlations were observed among maternal cardiac output, maternal body surface area and fetal birth weight. Discussion: i) This study shows that cardiac index and systemic vascular resistance index measured in the latter part of the second and third trimesters in hypertensive pregnant women were not associated with adverse fetal outcome. Large variations in cardiac index values were observed that restricted detection of satisfactory critical values for cardiac index and systemic vascular resistance index to predict adverse outcome. ii) An improved correlation of uterine artery resistance index with maternal hemodynamics and fetal birthweight in pre-eclampsia supports the hypothesis that poor placentation does not allow for a normal increase in uterine blood flow. iii) The poor correlation between uterine artery resistance index and maternal central hemodynamics, does not support the hypothesis that elevated cardiac output in hypertensive pregnancies (hyperdynamic disease model) occurs as a compensatory response to maintain adequate perfusion in a utero-placental bed with high resistance that did not decrease.Item Skin disorders in primary health care in KwaZulu-Natal : testing for solutions after assessment of burden of disease, and evaluation of resources.(2007) Aboobaker, Jamila B.; Abdool Karim, Salim Safurdeen.; Taylor, Myra.; Coovadia, Hoosen Mahomed.No abstract available.Item Time-course changes in the echocardiographic parameters and NT-proBNP levels in patients with severe mitral regurgitation undergoing valve replacement.(2007) Prakaschandra, Dorcas Rosaley.; Naidoo, Datshana Prakesh.Conventional echocardiographic parameters are currently used in determining the timing for surgery in patients with mitral regurgitation. Since brain natriuretic peptide (BNP) rises in response to ventricular muscle stretch, and is to detect early heart failure, we hypothesized that BNP would be activated in patients with regurgitant valvular heart disease and concomitant left ventricular dilatation. Aim/Objectives: We therefore studied the pattern of changes in NT-pro BNP in patients with chronic severe rheumatic mitral regurgitation who were undergoing mitral valve replacement and compared this with the newer modality of tissue Doppler imaging (TDI). Setting: Patients submitted to surgery were prospectively evaluated over 8 months at Inkosi Albert Luthuli Central Hospital, Department of Cardiology. Controls were obtained from the outpatients' follow-up clinic. Methods: Simultaneous quantification of the severity of mitral regurgitation (MR), left ventricular (LV) end systolic volume (ESV), left atrial (LA) volume and Doppler filling ratios (mitral (E)/annulus (Ea)) were performed at baseline in all patients and was repeated at 1-week and at the six-week follow-up visit in surgical patients. Results: Both groups were similar for age and gender and echo-Doppler parameters in all patients preoperatively except LA size (p< 0.01) and volume (p<0.004) which were more elevated in the surgical group. Mean NT-pro BNP levels were markedly elevated preoperatively (262 pmolll) in all surgical cases compared to controls (57 pmol/l; p=0.0001). NT-pro BNP levels increased further at one week post surgery (395 pmol/l) and subsided at the six week follow-up visit (94 pmol/I). These changes were accompanied by significant reduction in LA (p= 0.003) and LV chamber dimensions (EDD = 0.004) with an increase in the ejection fraction from 42% at one week to 52 % at six weeks. Four patients had abnormally elevated NT-pro BNP levels (>53pmol/l) at the 6-week follow-up visit. A ROC curve was constructed for all variables to separate surgical cases from controls. The area under the curve was highest for NT-pro BNP (sensitivity= 96%, specificity 45 %). Conclusion: 1. There was a significant difference in the left atrial chamber size and volume, as well as Em/Ea (TDI) and NT-proBNP levels preoperatively between the two groups. The lack of a significant difference in the LV parameters between surgical and control groups suggest an almost total reliance on symptoms in deciding the timing of surgery which was reflected by markedly elevated NT-pro BNP in all surgical patients. 2. Postoperatively, there was a significant reduction in LA and LV dimensions. 3. The high false positivity rate for NT-pro BNP suggests that the test is most likely reflecting early LV decompensation in the less symptomatic control patients who rightly need surgery. 4. Tissue Doppler indices had similar sensitivity but low specificity compared to NT-proBNP. 5. Serial estimations of NT-pro BNP may prove useful in selecting patients for surgery.Item The influence of helminths on immune responses to HIV.(2009) Mkhize-Kwitshana, Zilungile Lynette.; Walzl, Gerhard.; Taylor, Myra.In South Africa, co-infection with HIV and intestinal parasites is a major challenge in disadvantaged communities who live in densely populated under-serviced urban informal settlements. This pilot cross sectional study evaluates the immunological effects of co-infection with Ascaris lumbricoides and Trichuris trichura on the immune response to HIV. The work was a substudy of a prospective double blind, placebo-controlled investigation to test whether regular deworming changes the immune profile of HIV positive individuals with concurrent helminth infection. The substudy has a cross sectional design and presents pilot data that defines immune profiles of HIV-1 positive individuals with and without gastrointestinal helminth (Ascaris lumbricoides and Trichuris trichura) infection. The hypothesis was that concurrent helminth infection adversely affects immune responses against HIV. It was conducted in an area of high helminth endemnicity and limited infrastructural resources. Individuals with known HIV infection were recruited from an HIV Support Group and HIV negative individuals residing in the same area (for demographic matching) were used for comparison. The substudy was to provide pilot data for future larger scale and possible interventional studies. The current work is limited by the cross sectional design, moderate sample size and practical challenges. The profile of lymphocyte phenotypes, viral loads, eosinophils, activation markers, expression of the nuclear proliferation antigen-Ki67 and activation regulator antigen CTLA-4 were analysed using flow cytometry in HIV positive and negative subgroups with or without helminth infection. The type-1, type-2 and inflammatory cytokines were analysed using multiplex cytokine array technology. These were correlated with immune responses to HIV. Non parametric statistics were used to describe differences in the variables between the subgroups. A major finding of the study was the result of the supplementary use of the serological marker, Ascaris lumbricoides-specific IgE in addition to the presence (or absence) of helminth eggs in stools to classify intestinal helminth infection status. Two significant outcomes of this measure were the enhancement of diagnosis of current or recent helminth infection and, more importantly, the distinction of different phenotypes of individuals who displayed different immunological responses to co-infection with HIV and helminths. The different helminth infection phenotypes are defined by stool egg positivity (egg⁺) or negativity (egg⁻) with either high or low Ascaris-specific IgE (IgEhi or IgElo) respectively. The four subgroups, egg⁺IgEhi, egg⁺IgElo, egg⁻IgEhi and egg⁻IgElo showed different interactions with regards to immune response to HIV. It should be noted that no Trichuris specific IgE tests are commercially available but that there is significant antigenic cross-reactivity with Ascaris antigen. The presence of helminth stool eggs and high Ascaris IgE (egg⁺IgEhi) was associated with the following characteristics: reduction in numbers of all lymphocyte populations, frequent eosinophilia, highly activated immune profiles, antigen specific proliferative hyporesponsiveness, impaired type 1 cytokine responses in unstimulated and antigen stimulated cells and increased TNFα levels. In HIV infected individuals, the egg⁺IgEhi helminth infection status was associated with lower but not significant CD4⁺ counts and higher viral loads. A strong negative correlation was observed between viral loads, CD4⁺ and CD8⁺ cells in this subgroup. Subgroups with high IgE (egg⁺IgEhi and egg⁻IgEhi) had elevated Th2 markers with lower CD4⁺ counts and higher viral loads in the HIV⁺ group. The inverse correlation between viral load and CD4⁺ counts found in all the HIV⁺ participants was strongest in these two subgroups. Individuals with parasite eggs in stool and low Ascaris IgE (egg⁺/IgElo) presented a modified Th2 profile. This subgroup had high absolute numbers of all lymphocyte subsets in both HIV⁻ and HIV⁺ groups with higher CD4⁺ counts in the HIV⁻ and lower viral load in the HIV⁺ groups as well as higher interferon gamma, lower IL-4 and higher IL-10. In conclusion, the results suggest that helminth infections may be associated with deleterious effects on the immune responses to HIV in certain groups of susceptible individuals. The underlying reasons for the different stool egg/Ascaris IgE combinations in settings with high exposure to helminthes is currently not clear but genetic predisposition and environmental factors could play a role. Future studies of helminth- HIV co-infection have to ensure adequate definition of helminth infection status by the use of both stool examination and measurement of helminth-specific IgE as the infection phenotype is associated with differential effects on HIV associated immune responses. This may also apply to co-infection with other pathogens, including tuberculosis. The long-term effect of helminth co-infection in HIV positive people was not assessed in this study but requires further studies.Item Effects and mechanisms of interleukin-10 promoter polymorphisms on HIV-1 susceptibility and pathogenesis.(2012) Naicker, Dshanta Dyanedi.; Ndung'u, Peter Thumbi.HIV infection has risen to pandemic proportions. Interleukin-10 (IL-10), a potent antiinflammatory cytokine has been shown to enhance the establishment and persistence of chronic viral infections through inactivation of effector antiviral immune responses and it may also directly influence HIV-1 replication in cells of diverse lineages. IL-10 promoter polymorphisms have been shown to affect HIV-1 susceptibility and pathogenesis. However, the underlying mechanisms are poorly understood. We investigated the relationship between IL-10 promoter variants, plasma IL-10 levels, and markers of disease outcome in chronically HIV-1-infected individuals. To investigate the mechanistic role of IL-10 and its genetic variants on HIV pathogenesis, we studied markers of activation on B cells, CD4+ and CD8+ T cells, and assessed effects on CD4+ T cell proliferation with and without blockade of the IL- 10 pathway. We used Taqman genotyping assays to genotype three IL-10 promoter single nucleotide polymorphisms (SNPs) in our study cohort. Baseline plasma IL-10 levels were measured using Luminex technology for 112 individuals. Viral load, CD4+ T cell counts and cytotoxic T lymphocyte (CTL) immune responses were measured at baseline. The rate of CD4+ T cell decrease was calculated in 300 individuals with a median follow-up of 25 months. CD38, CD95, Ki67, IgG and PD-1, markers of activation or exhaustion were measured on B cells, and CD38, CD95, Ki67, HLA-DR and PD-1 were measured on CD4+ and CD8+ T cells in a subset of 63 individuals. CD4+ T cell proliferation was measured using Carboxyfluorescein succinimidyl ester (CFSE) assays, following IL-10 receptor blockade in a subset of 31 individuals. The IL-10 -1082G, -592A and -3575 variants were observed at frequencies of 0.3, 0.34 and 0.23 respectively, in our study cohort. Plasma IL-10 levels were significantly higher in the - 1082GG group than in the combined AA/AG group (p=0.0006). There was a significant association between the 592AA genotype and a greater breadth of CTL responses compared to the CC and CA (p= 0.002 and 0.004 respectively). The -592AA genotype associated significantly with an attenuated loss of CD4 cells (p= 0.0496), with -592AA having the least change in CD4 cells per year. The median expression of HLA-DR, a marker of T cell activation was significantly higher in the-1082AA group for CD8 cells (p= 0.047), and the - 592AA group for CD4 T cells (p= 0.01). The median expression of IgG on the surface of B cells was significantly higher in the -1082GG genotype and the -592CC genotype (p=0.0183 and 0.0659 respectively). Overall, IL-10 variants correlated with IL-10 expression and CD4 decline during chronic HIV-1 infection. IL-10 promoter variants may influence the rate of HIV-1 disease progression by regulating IL-10 levels, which in-turn, may affect the breadth of CTL responses. Furthermore, the increased expression of HLA-DR and PD-1 on CD8+ and CD4+ T cells, indicates that lower IL-10 levels are associated with increased immune activation and immune exhaustion. The increased expression of IgG on B cells, suggests that in a setting of lower IL-10, there is possibly a bias towards a Th2 immune response. These data suggest a significant role for IL-10 genetic variants and IL-10 in HIV pathogenesis. Further studies to determine whether and how the IL-10 pathway may be manipulated for therapeutic or vaccine strategies for HIV are warranted.Item Hip fracture and osteoporosis : a comparison of the demographic profile, risk factors, outcomes and health care costs in geriatric patients with and without osteoporotic hip fractures in the public health sector in the eThekwini area.(2014) Paruk, Farhanah.; Cassim, Bilkish.Abstract available in PDF file.Item Exploring the impact of experience-based medical learning on students' clinical preparedness : a case study of the South African-Cuban medical training collaboration programme at the University of KwaZulu-Natal, South Africa.(2014) Motala, Munirah Ismail.; Van Wyk, Jacqueline Marina.Background: The South-African-Cuban Medical Collaboration (SACMC) programme involves medical training being offered to rural South African (SA) origin students in Cuban facilities with the view of future medical practice in local rural SA settings. The students on the SACMC programme return to South African medical schools to complete their training and clinical practice in their 4th academic year. The students experience difficulty in adapting to local clinical demands and integrating their prior knowledge as required at the Nelson R Mandela, School of Medicine, (NRMSM) of the University of KwaZulu-Natal (UKZN) in Durban, South Africa as evidenced from examination board minutes. Aim: In an effort to inform educators of the extent to which students’ prior clinical training and experiences in Cuba matched the clinical skills taught at the NRMSM, this study investigated the similarity or difference in approach to the curriculum, clinical skills content and perceived competence of the SACMC students to a set of 75 core clinical skills which are deemed essential during training in years 1-3 at the institution. Methods: A mixed methodology study used a phenomenological approach to explore the clinical experiences of 11 South-African-Cuban medical collaboration students. Qualitative data collected by means of interviews and a questionnaire were used to determine the curriculum approach and content. A questionnaire generated quantitative data about students’ familiarity; exposure and perceived competence (ability to perform independently, with supervision or not at all) on 75 specific skills which are considered a prerequisite to enter the 4th academic year at the NRMSM. The skills in 9 major categories, included communication, resuscitation, adult examination, new-born examination, general procedural skills, specimen collection, obstetrics and gynaecology procedures, airway management procedures and radiological examination. Findings: The didactic, lecture intensive Cuban curriculum with its emphasis on primary health care principles and predominance of ward-based clinical training was found to be vastly different from the problem-based, systematic and practical oriented laboratory-based clinical training offered to local students. The majority of students self-reported a lack of exposure to 35 of the overall 75 identified skills. Most students claimed an inability to independently perform 95% (4 out of 75 skills- able to perform 5%) of clinical skills. The qualitative data revealed that many primary health care skills were neither taught nor practiced by students within the first 5 years of training in Cuba. Conclusion: This study has highlighted the mismatch between the focus and scope of clinical training offered to students on the South African-Cuban Medical Collaboration programme and those at the NRMSM. In the light of continued collaboration in health education and to ensure that returning students are adequately supported and integrated into the SA clinical setting, it is important that educators work towards improving the alignment of the training programs.Item An explorative review of the distribution, incidence, prevalence, diabetes related amputations and defaulters of patients with diabetes mellitus and podiatrists in the public health care sector of KwaZulu-Natal.(2015) Sahadew, Nikita.; Singaram, Veena S.; Brown, Susan Lynn.The prevalence of diabetes is increasing globally, especially in African countries, where 62% of cases are undiagnosed and are seen by a medical professional only once complications have manifested. Among the tangle of complications, the diabetic foot is a cause of morbidity and mortality. The management of foot ulcerations, non-ulcerative pathologies and the prevention of subsequent amputation is a challenge, resulting in physiological, psychological and economic consequences. Including a podiatrist in the multidisciplinary healthcare team involved in the care of the lower limbs of the diabetic patient has the potential to improve patient outcomes and reduce the economic burden incurred by both the patient and the state. The global increase in the prevalence of diabetes is most marked in African countries. The District Health Information System (DHIS) is the primary data collection system of the Department of Health in KwaZulu- Natal (KZN). Data is routinely collected at all public healthcare facilities in the province and is aggregated per facility. This study aimed to investigate the distribution of diabetic patients and podiatrists in the public health sector of the eleven KZN districts. A retrospective audit was conducted of the KZN Department of Health databases on diabetes in and between the years 2010 and 2014. The data was cleaned, tested for capture errors, verified and analysed. Using pivot tables, derived metrics, and graphs using Microsoft Excel were constructed. Additional open source databases were accessed to allow further exploration of the data collected. The prevalence of diabetes in the public health sector of KwaZulu-Natal was found to be 14.3% higher than national prevalence estimates. Thirty-eight per cent of the cases were found in the highly urbanised district of eThekwini. A total of 1 329 275 diabetic patients were recorded and, according to national guidelines for the treatment of diabetes, required podiatric care. However, only two podiatrists work in the KwaZulu-Natal public health sector. The number of podiatrists is totally insufficient to serve the growing diabetic population in this province’s public health sector. A major infusion of more podiatry graduates, appropriate distribution and inclusion of podiatric services into the diabetic foot care team needs to therefore be considered to enable compliance with national and international diabetic foot care guidelines. In the interim, existing public health care practitioners can be educated to offer diabetic foot care information to the patient and on the correct referral patterns to allow the patient access to a podiatrist. The findings of this study are consistent with the well-established relationship between diabetes and urbanisation. Correlation calculations support the assumption of a directly proportional relationship between diabetes prevalence and the number of diabetes-related amputations. This study highlights the need for at least 319 podiatrists in the province of KwaZulu-Natal to satisfy the national guidelines for minimal diabetic care regarding assessment, screening and education of patients only; not considering the treatment of existing and future foot complications. Short and long term recommendations such as changes in the data collection process at public health facilities and the assessment of existing tertiary medical institutions for the establishment of additional departments of podiatric medicine can greatly contribute to addressing the calculated shortage of podiatric practitioners in the public health sector.Item Reproductive health in women following sterilisation in Durban, South Africa.(2016) Kistan, Gaysheen.; Panday, Mala.Abstract available in PDF file.Item Snakebite in KwaZulu-Natal: the burden of disease and prediction of risk of adverse outcomes.(2016) Wood, Darryl Ross.; Hift, Richard Jefcoate.BACKGROUND The total number of snakebites per annum in KwaZulu-Natal (KZN) is unknown. Yet it is believed that the burden that snakebites place on hospitals in areas with a high incidence of snakebite is significant. There are no official snakebite guidelines in South Africa or KwaZulu-Natal. The result is non-uniform management practices and in many cases inappropriate prescribing of antivenom, which may potentially be harmful given a high rate of allergic reactions to antivenom. In order to standardise practice along evidence-based lines, it is important to identify factors predictive of a poor outcome so that treatment can be appropriately targeted at those individuals. AIMS 1. To determine a figure for the annual incidence of snakebite, identify regional variations in incidence and estimate the burden of snakebite on public hospitals in the north-eastern province of KwaZulu-Natal, an area in which snakebite is endemic. 2. To report a five-year prospective experience with snakebite in a highly endemic area of South Africa and to identify factors predictive of severity. 3. To develop and validate a severity scoring system to facilitate the management of snakebite in South Africa by allowing early identification of patients at increased risk of a severe course, and thereby develop an improved algorithm for the management of snakebite. 4. To determine the site of expansion accounting for the swelling in patients bitten by a cytotoxic snake species, in particular to distinguish between muscle compartment swelling and superficial swelling, and to determine the clinical utility of bedside ultrasonic examination as a potential tool for identifying patients with possible compartment syndrome. METHODS The work is reported as four sub-studies, using a selection of methodologies appropriate to each, which are fully described in Chapters 2-7. In order to determine incidence of snakebite, we applied a novel method whereby incidence was extrapolated from antivenom supply data provided by the central provincial pharmacy depot, with the appropriate conversion factor being determined from a stratified a sample of 6 hospitals. We analysed prospectively captured data on all patients admitted to Ngwelezane Hospi Emergency Department from September 2008 to December 2013 with a diagnosis of snakebite. Using the need for an active treatment intervention (ATI), which we defined as antivenom administration or surgical intervention as a proxy for severity, we analysed our data for factors present on admission which were predictive of severity. In a subsequent study, we developed a severity score on a cohort of patients, which was then validated in a separate and subsequent cohort of patients. We developed a methodology for the assessment of depth of bite in patients bitten on a limb whereby the ratio of the thickness of the deep muscle compartment and the subcutaneous compartment of the bitten limb, measured by bedside ultrasound, were expressed proportionally, and compared with the ratio on the unaffected limb. This information was then used to identify the major site of swelling. RESULTS Incidence We estimated that 11% (95% CI: 8-14%) of snakebite presentations to hospital resulted in the administration of antivenom. By extrapolation, the overall incidence for KZN was 16/100 000. There was wide geographic variation, with the highest incidence, at 82/100 000 in the subtropical north east of the province. The estimated annual cost of snakebite in KZN was between USD 1 135 782 and USD 2 877 314. Analysis of a case series and prediction of severity 879 cases were analysed. Envenomation was identified in over two thirds of admissions. Cytotoxic snakebites accounted for 98% of envenomations. Only 4 cases of haemotoxic bleeding and 5 cases of neurotoxicity were admitted. Although we demonstrated a significant correlation between severity and prolonged INR, reduced platelet count, haemoglobin, reduced or elevated leucocyte count and elevated serum urea. However, their use as predictors of severity was limited by poor sensitivity and specificity. Clinical factors correlating with severity were the paediatric age group and a delayed presentation to hospital. In the prospective study, 146 of 879 snakebite admissions in the development cohort and 40 of 100 in the validation cohort reached the primary end point of an ATI. Six predictors of risk for ATI were identified from the development cohort: age <14 years, delay to admission >7 hours, white cell count > 10x109 cells/l, platelet count<92 x109/l, haemoglobin <7.1 g/dl, INR >1.2. Each risk predictor was assigned a score of 1; ROC curve analysis returned a value of more than 4 out of 6 as the optimal cut-off for prediction of an ATI (AUC 0.804; 95% CI 0.758-0.84). Testing of the score on the validation cohort produced a sensitivity of 22.5% and a specificity of 96.6%. The PPV and NPV were 81.8% and 65.2% respectively. Ultrasonic determination of the site of swelling in cytotoxic envenomation The majority of bites were in the upper limb (27/42). Tissue expansion was noted in both the sub-cutaneous and muscle compartments of the envenomed limbs. The site of swelling was predominantly in the subcutaneous tissues, while swelling in muscle compartment was limited (the mean expansion coefficient for subcutaneous tissues was 2.0 (CI: 1.7-2.3) versus 1.06 (CI: 1.0-1.1) respectively). The difference between the groups was significant (P<001). One case, confirmed as compartment syndrome, showed marked swelling in the muscle group and stood out as a clear outlier in terms of the expansion coefficient. CONCLUSIONS The burden of snakebite is substantial, and is felt unequally across the province. Furthermore, we propose that our method may be used to estimate the incidence of other diseases treated with a standard regimen and for which incidence figures are otherwise unknown. Two-thirds of patients who present to hospital with snakebite in north-eastern South Africa will have symptoms of envenomation, with the overwhelming majority manifesting cytotoxicity. Bites by neurotoxic and haemotoxic species are rare. We have identified a number of factors which may potentially be of value in predicting severity, but which are on their own of insufficient accuracy to be reliable. Basic ultrasound techniques may be used to identify the site and degree of tissue swelling from cytotoxic envenomation. It is a non-invasive, painless procedure that can assist the clinician to assess the injured limb and may also be of benefit to monitor the progression of swelling. Our scoring system, which we propose to name the Zululand Snakebite Severity Score (ZSSS), is a useful adjunct to clinical assessment in managing snakebite. A patient with a positive result has an 80% probability of progressing to the point where an ATI is indicated. Its value is greatest in those patients who fall in the mild to moderate clinical category. This score now requires validation on a wider scale across South Africa, to determine its accuracy in areas other than those in which it was tested.Item Resistance to β-lactam and fluoroqinolone antibiotics in enterobacteriaceae from chicken : an observational study in Maputo, Mozambique.(2016) Faife, Sara Lino.; Essack, Sabiha Yusuf.; Sundsfjord, Arnfinn Staale.; Zimba, Tomas Francisco.Extended-spectrum β-lactamase (ESBL) and/or plasmid-mediated AmpC (pAmpC)-producing Enterobacteriaceae with co-resistance to fluoroquinolones are increasingly identified in food-borne pathogens globally. This study investigated ESBL- and pAmpC-mediated β-lactam resistance as well as plasmid-mediated fluoroquinolone resistance in 198 samples taken from 99 frozen chickens (99 samples from the liquid thaw and 99 from carcass swabs), Brazil, South Africa and Mozambique each produced 33 chicken. Species identification was undertaken using in-house biochemical tests and antibiotic susceptibility was ascertained by the disc diffusion test following CLSI guidelines. ESBL production was determined using the double-disk synergy test and isolates were subjected to PCR to detect the presence of blaCTX-M, blaSHV, blaTEM, blaCMY, blaMOX, blaFOX, blaDHA, qnrB, qnrD, qnrS and qepA genes. A random selection of CTX-M genes was sequenced. The 198 samples yielded 27 putative ESBL-positive isolates: Citrobacter diversus (1), Citrobacter freundii (3), Enterobacter aglomerans (1), Enterobacter cloacae (1) and Escherichia coli (21). Of the 27 isolates, 19 were from South African chicken, five from Mozambican chicken and three from Brazilian chicken. Resistance to ampicillin was 100,0%, followed by 88.8% to ceftriaxone, 77.8% to trimethoprim-sulphamethoxazole, 74.0% to cefotaxime, 70.4% to ciprofloxacin, 66.6% to ceftazidime, 22.2% to cefoxitin and 7.6% to gentamicin. Multi-drug resistance was evident in 19 (70.4%) isolates, 15 of which were from South Africa. The predominant ESBL gene was blaSHV (85%), followed by blaCTX-M (62.9%) and blaTEM (44.4%) whilst blaMOX (33, 3%) and blaDHA (33.3%) were the most common pAmpC genes. The predominant plasmid-mediated fluoroquinolone-resistance gene was qepA (22.2%). DNA sequencing of the blaCTX-M genes putatively identified differentiation of the E. coli and Citrobacter spp. isolates. There was no strong evidence of clonality, however, South African isolates shared more similarity. qnr and qepA genes were predominantly identified in South African E. coli isolates while CTX-M and SHV genes were prevalent in isolates from diverse origins. The Mozambican population is thus exposed to a reservoir of plasmid-mediated and hence, mobile β-lactam and fluoroquinolone resistance genes from imported, and to a lesser extent, locally-produced chicken. The complexity and diversity of mobile resistance genes combinations and permutations is of concern in the food safety context.blaCTX-M-55/-79/-101/-164, with blaCTX-M-164 being most common. ERIC–PCR profiles allowed the differentiation of the E. coli and Citrobacter spp. isolates. There was no strong evidence of clonality, however, South African isolates shared more similarity. qnr and qepA genes were predominantly identified in South African E. coli isolates while CTX-M and SHV genes were prevalent in isolates from diverse origins. The Mozambican population is thus exposed to a reservoir of plasmid-mediated and hence, mobile β-lactam and fluoroquinolone resistance genes from imported, and to a lesser extent, locally-produced chicken. The complexity and diversity of mobile resistance genes combinations and permutations is of concern in the food safety context.Item Radiologic evaluation of breast disorders related to tuberculosis amongst women in Durban, KwaZulu-Natal, South Africa.(2016) Ramaema, Dibuseng Paulina.; Somers, Sat.; Hift, Richard Jefcoate.Women in KwaZulu-Natal Province, South Africa, are at high risk of developing breast tuberculosis (BTB) due to the increased incidence of HIV. However, there is a general lack of knowledge regarding the various diseases that can affect the breast. This is compounded by lack of the national breast screening program. As a result, many patients with breast cancer (BCA) and BTB are initially misdiagnosed by clinicians. It was evident from the study that much still has to be done in educating the public and healthcare workers about breast diseases. This project endeavoured to compare the effectiveness of various radiological technologies to identify breast problems. The study consisted of three phases all based at Ethekwini Municipality tertiary referral hospitals. The first phase aimed to determine the prevalence of the BTB using retrospective data over a period of 13 years. The same data further provided information of the clinical and radiological manifestations of BTB. This study concluded that while BTB is not common, it shares the clinical and radiology features with BCA, and is difficult to diagnose with current pathology methods. The second phase was done prospectively by recruiting patients who were newly diagnosed with BTB. The aim was to evaluate the use of modern imaging techniques to further describe the radiology patterns of BTB and to determine the radiological parameters that may be used in disease monitoring. The results provided insight into disease extent, and showed that it is usually more severe than perceived with current diagnostic methods. The third phase was performed using retrospective image analysis of patients who had BCA and BTB by using modern radiology techniques. The purpose was to identify the salient features that can differentiate BTB from the BCA. Several radiology parameters were identified as possible biomarkers for differentiation between the two conditions. The knowledge of their respective features would aid in the timeous diagnosis of both conditions, particularly in cases where the pathology results are inconclusive for various reasons. Overall the study highlights the lack of evidence based information on BTB. Recommendations and conclusions are provided in the last chapter.Item Does gender impact on female doctors' experiences in the training and practice of surgery?(2016) Umoetok, Flora.; Van Wyk, Jacqueline Marina.; Madiba, Thandinkosi Enos.Abstract available in PDF file.Item Epidemiology of chronic kidney disease in KwaZulu-Natal: evaluation of risk factors, complications and diagnostic methods.(2017) Madala, Nomandla Daphne.; Assounga, Alain Guy Honore.Chronic kidney disease (CKD) is associated with increased morbidity and mortality as well as costly renal replacement therapy. The aim was to determine risk factors and complications that contribute to morbidity as well as a suitable diagnostic detection method for CKD. Methods Observational studies were done at 2 hospitals. To assess risk factors, 283 patients were included at the Durban site, and sub-studies undertaken within this sample for CKD complications, while 302 patients were studied at the Empangeni outreach site. To evaluate predictive performance of estimated glomerular filtration rate (eGFR), data from 148 patients were analysed. A further 76 patients were recruited, to develop an African equation. Cockcroft Gault, Modified Diet in Renal Disease and CKD Epidemiology Collaboration eGFR equations were compared with technicium-99-mdiethylenetriaminepentaacetic acid (99mTc-DTPA)-GFR as the gold standard. Body composition was assessed by anthropometry and dual energy X-ray absorptiometry. Data were analysed with STATA. Results The commonest CKD risk factors were hypertension (75%), diabetes (29%) and human immunodeficiency virus (HIV) infection (24%), with HIV commoner at the outreach site (28.5% vs 19.8%). Over 80% of females and ∼60% males were overweight/obese overall; however, clinical cardiovascular disease was commoner in Durban (28% vs 5%). Complications were observed in early CKD; prevalence increased as eGFR declined from ≥90 ml/min/1.73m2 to <30 ml/min/1.73m2: hyperuricaemia increased from 17% to 74%, metabolic acidosis (11.6% to 72.7%), anaemia (2.9% to 69.7%), hyperphosphataemia (10.1% to 48.5%), all p<0.001, respectively, and hypocalcaemia from 1.5% to 18.2% (p=0.003). Lower GFR levels were also associated with lower serum albumin levels, and lower whole body as well as regional lean mass and fat mass in males. A further observation at GFR <30 ml/min/1.73m2 was that eGFR underestimated 99mTc-DTPA-GFR in African patients. Prediction of 99mTc DTPA-GFR was also poor at GFR levels ≥60 ml/min/1.73m2, with eGFR overestimating 99mTc-DTPA-GFR. An eGFR equation developed in African patients resulted in significantly better GFR prediction and showed the lowest bias, highest precision as well as accuracy. Conclusion Efforts are needed to enable non-nephrologists to manage CKD risk factors and complications. Prediction of GFR may be substantially improved by using an equation developed in Africans.Item A cross-sectional descriptive study of pre-hospital care providers’ training, knowledge and skills in austere environments emergency medicine in South Africa: a framework for a consensus statement for Wilderness Emergency Medicine.(2017) Matthew, Jaybalan Allan.; Maharaj, Roshen.; Clarke, Damian Luiz.There is a lack of research into the resource capabilities and capacity for wilderness emergency medicine practice in South Africa (SA). This is despite SA having vast expanses of populated austere geography that remains difficult to access by conventional health care systems and the country increasingly becoming an attractive ecotourist destination. With increasing needs for skilled health care personnel to deal with medical emergencies in this environment, it is first necessary to determine the extent of the current resources present within SA. This research looked at the human resource potential to deal with medical emergencies in the wilderness emergency environment in SA. Chapter one considers the conceptual and contextual framework of this research in light of the above and a review of the available literature. Chapter two presents research from a study that determined the self-reported extent of training, knowledge and skills that capacitated Emergency Care Practitioners (ECP) registered with the Health Professions Council of South Africa (HPCSA) when operating in the wilderness environment and when dealing with medical emergencies. Chapter three examines data gained from a survey conducted among emergency medicine specialists regarding the competency in knowledge, training and skills that are ideally required in the practice of wilderness emergency medicine (WEM). Chapter four compares the self-reported knowledge, training and skills of ECPs in the wilderness emergency environment, with what is suggested by emergency medicine specialists as the expected level of knowledge, training and skills for practice in this field. Chapter five presents a published editorial that highlights the potential value of this specialised WEM practice in resource-limited countries. This editorial suggests that proper wilderness emergency medicine training, knowledge and skills could perhaps be an alternative solution for frugal innovation for resource-limited pre-hospital and inhospital practice. There is a need for further training and skills uptake in WEM. Additionally, a local framework for a consensus statement on the practice of WEM needs to be established.Item Admissions for pulmonary embolism at a tertiary South African hospital.(2017) Kistensamy, Sivaisen Ricardo.; Moodley, Yoshan.; Brown, Susan Lynn.Background: Published descriptions of pulmonary embolism (PE) from South African (SA) settings are rare. We sought to address this gap in the literature. Methods: This was a case series involving 61 adult patients admitted to a tertiary SA hospital over a five-year period with a primary diagnosis of PE. Data related to patient demographics, PE presentation, risk factors, treatment, and inpatient mortality were collected and analysed using appropriate statistical tests. Results: Most of our study population were younger (86.9%), female (67.2%), and of black African ethnicity (73.8%). Dyspnoea and chest pain were the most common symptoms (prevalence of 86.9% and 41.0%). Prevalent clinical signs included tachypnea (47.5%) and tachycardia (42.6%). The most prevalent established risk factors were cardiac failure (49.2%) and a history of deep vein thrombosis (up to 19.7%). Massive PE was diagnosed in 8.2% of study patients. Most patients received anticoagulation therapy (95.1%), with thrombolysis and embolectomy performed only in smaller proportions (24.6% and 11.5%) of patients. The incidence of inpatient mortality was 23.0%. Characteristics associated with mortality included: admission route (p=0.008), dyspnoea (p=0.002), tachycardia (p<0.001), and embolectomy (p=0.042). Conclusion: Our study findings have important implications related to the management of PE in SA.Item Adherence to iron prophylactic therapy during pregnancy in an urban regional hospital in Durban, South Africa.(2017) Mkhize, Princess Zinhle.; Moodley, Jagidesa.; Naicker, Thajasvarie.Iron and folic acid supplementation plays a major role in prevention and control of iron deficiency anaemia in antenatal care. In South Africa, although all pregnant women receive iron, folate and calcium supplementation throughout pregnancy, anaemia is still common. Low adherence may be a key contributor to the ineffectiveness of supplementation programs.Therefore, this study was conducted to examine adherence to prophylactic iron supplementation during the antenatal period. An observational clinical study was conducted in a regional hospital from January- December 2016. Women (n=100 HIV uninfected and n=100 HIV infected) were recruited and subdivided into three groups: (a) 1st attendees ≤ 34 weeks (n=33), (b) 34-36 weeks (n =34) and (c) ≥ 37 weeks /birth (n=33) respectively. A structured questionnaire was used for data collection. Data were coded and computed onto an excel sheet for statistical analysis using SPSS software. Data from women (n = 24) from 1st visit attendees ≤ 34 weeks and 34-36 weeks subgroups indicated that pill count and self-reported data reflected 50% adherence and 46% non-adherence, being higher in the HIV infected women (75%). Nausea was the commonest side effect in all trimesters (79, 2%). Adherence (27.8%) and non-adherence (72.1%) to iron, folic acid and calcium supplementation were observed in 176 (88%) women. Promoting essential strategies on the importance of consumption and effectiveness of iron prophylactic therapy is essential to maintain and improve anaemia in antenatal attendees during pregnancy.Item Application of communication skills in an authentic clinical setting: assessing the communication competency of sixth year medical students during history taking.(2017) Ntando, Ekanda Alfred.; Van Wyk, Jacqueline Marina.; Matthews, Margaret Glynnis.The Nelson R. Mandela School of Medicine (NRMSM) launched a new 6 year MBChB programme in 2010. This curriculum includes a clinical communication course which emphasises the patient centred approach in line with the Health Professions Council of South Africa Core Competency Framework for undergraduate students. The Calgary-Cambridge Guide to the Medical Interview was adopted as a method for teaching communication. The 2015 final year medical students constituted the first cohort to have been taught clinical communication skills in this manner in the pre-clinical phase. Aim of the study The study was conducted to investigate the transfer of communication skills taught using the Calgary-Cambridge Method (CCM) in the pre-clinical phase to the clinical setting. This study focused mainly on the process skills of history taking and had the following objectives: 1. to determine whether students used the CCM as taught at medical school. 2. To measure and compare process skills of students in two different phases of MBChB programme. 3. To explore role modelling of the CCM by clinical teachers. 4. To describe challenges encountered by students for or in the application of the CCM. Methods The study was observational, analytical and cross-sectional. The population was the 2015 final year class of medical students (n=198) with exception of 13 students who were trained in a different method in Cuba. The study was conducted in the Internal Medicine wards of four teaching hospitals affiliated to the medical school in the Durban functional region. Results The population of the study comprised 185 eligible students; 107 participants were enrolled, and the final number of participants was 105 (57%). In response to the four objectives of the study, the findings revealed that most students used the CCM in a modified manner. There was a marked decline in some of the process skills of history taking, specifically in subcategories such as providing structure and eliciting the patients’ perspective. Educators in Internal Medicine wards did not model the use of the CCM and discouraged its application due to workload and time constraints. Challenges encountered by students included negative attitudes of clinical trainers towards the CCM and language barriers, as most patients spoke in isiZulu. Discussion Results demonstrated that the clinical communication teaching and learning of the pre-clinical phase had some positive impact on application, even if students only used the Calgary Cambridge Method in a modified manner in the clinical phase. The environment of clinical training influenced the transfer, development and the progress of the communication skills learnt in the pre-clinical phase. The decline of process skills in providing structure and eliciting the patient’s perspective was associated with negative attitudes and the poor role modelling of educators. This observation is contradictory to the increase shown in the process skills of building relationship and initiating the session, which probably reflects students’ accumulated experience in the wards. Students encountered challenges associated with language barriers and with different approaches used for personal and organizational reasons. Conclusion With regard to students’ attainment of the HPCSA core competency of communication, and despite communication teaching in the pre-clinical phase and its application in the disciplines of Family Medicine and Rural Health, communication was not equally valued or reinforced in all disciplines involved in undergraduate teaching on the MBChB programme. Key words: communication skills, transfer, application, clinical settingItem The effect of HIV infection on the management of end-stage renal failure among patients undergoing continuous ambulatory peritoneal dialysis.(2017) Ndlovu, Kwazi Celani Zwakele.; Assounga, Alain Guy Honore.Continuous ambulatory peritoneal dialysis (CAPD) is cost effective, easy to learn, and requires no complex equipment, thus, is well-suited as a home dialysis modality in areas with distant or limited dialysis facilities. We aimed to evaluate the effects of HIV infection on CAPD outcomes in dialysis-requiring end-stage renal disease (ESRD) patients. The first report (Chapter 2) evaluated the effects of HIV-infection on primary end points of mortality and catheter failure, and primary morbidity outcomes of first peritonitis and hospital admissions at one year. HIV infection was not shown to adversely influence catheter failure rates or patency; however, uncontrolled HIV infection was associated with increased relative risk of mortality, first peritonitis, and hospital admissions. The second report (Chapter 3) evaluated the effects of HIV infection on all peritonitis episodes, including relapses and subsequent episodes at 18 months. HIV infection was associated with increased risk for overall peritonitis and peritonitis relapse. Although peritonitis was also associated with adverse catheter failure outcomes, HIV infection was not shown to result in significantly increased catheter failure rates at 18 months. The third report (Chapter 4) evaluated the effects of HIV infection on nasal carriage of Staphylococcus aureus, staphylococcal peritonitis, and catheter infection rates. HIV infection was shown to be a risk factor for methicillin-resistant S. aureus nasal colonisation, and that it can increase the risks of coagulase-negative staphylococcal peritonitis and S. aureus catheter infections in association with S. aureus nasal carriage. The fourth report (Chapter 5) evaluated shedding of HIV-1 particles into CAPD effluents. HIV particles were shown to be shed in detectable amounts into CAPD effluents even in patients with suppressed plasma viral load, raising concerns of a localised sanctuary site and potential infectivity of HIV-positive CAPD patients on a full complement of antiretroviral therapy. The thesis contributes to our understanding of the morbidity and mortality associated with uncontrolled HIV infection in ESRD patients on CAPD, the shedding of HIV-1 particles into CAPD effluents, and the resistance profiles of S. aureus colonisers and the organism patterns that are likely to cause infection, which may assist in guiding appropriate antibiotic therapy and prophylaxis.