Browsing by Department "Department of Medicine"

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    Open Access
    A 52-Week Placebo-Controlled Trial of Evolocumab in Hyperlipidemia
    (2014) Blom, Dirk J; Hala, Tomas; Bolognese, Michael; Lillestol, Michael J; Toth, Phillip D; Burgess, Lesley; Ceska, Richard; Roth, Eli; Koren, Michael J; Ballantyne, Christie M; Monsalvo, Maria Laura; Tsirtsonis, Kate; Kim, Jae B; Scott, Rob; Wasserman, Scott M; Stein, Evan A
    BACKGROUND Evolocumab, a monoclonal antibody that inhibits proprotein convertase subtilisin/ kexin type 9 (PCSK9), significantly reduced low-density lipoprotein (LDL) cholesterol levels in phase 2 studies. We conducted a phase 3 trial to evaluate the safety and efficacy of 52 weeks of treatment with evolocumab. METHODS We stratified patients with hyperlipidemia according to the risk categories outlined by the Adult Treatment Panel III of the National Cholesterol Education Program. On the basis of this classification, patients were started on background lipid-lowering therapy with diet alone or diet plus atorvastatin at a dose of 10 mg daily, atorvastatin at a dose of 80 mg daily, or atorvastatin at a dose of 80 mg daily plus ezetimibe at a dose of 10 mg daily, for a run-in period of 4 to 12 weeks. Patients with an LDL cholesterol level of 75 mg per deciliter (1.9 mmol per liter) or higher were then randomly assigned in a 2:1 ratio to receive either evolocumab (420 mg) or placebo every 4 weeks. The primary end point was the percent change from baseline in LDL cholesterol, as measured by means of ultracentrifugation, at week 52. RESULTS Among the 901 patients included in the primary analysis, the overall least-squares mean (±SE) reduction in LDL cholesterol from baseline in the evolocumab group, taking into account the change in the placebo group, was 57.0±2.1% (P<0.001). The mean reduction was 55.7±4.2% among patients who underwent background therapy with diet alone, 61.6±2.6% among those who received 10 mg of atorvastatin, 56.8±5.3% among those who received 80 mg of atorvastatin, and 48.5±5.2% among those who received a combination of 80 mg of atorvastatin and 10 mg of ezetimibe (P<0.001 for all comparisons). Evolocumab treatment also significantly reduced levels of apolipoprotein B, non-high-density lipoprotein cholesterol, lipoprotein(a), and triglycerides. The most common adverse events were nasopharyngitis, upper respiratory tract infection, influenza, and back pain. CONCLUSIONS At 52 weeks, evolocumab added to diet alone, to low-dose atorvastatin, or to high-dose atorvastatin with or without ezetimibe significantly reduced LDL cholesterol levels in patients with a range of cardiovascular risks.
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    Open Access
    A clinical audit of the management of ADHD in children and adolescents and comparison between two treatment sites in Cape Town
    (2014) Vrba, Kim; Voge, Wendy; de Vries, Petrus J
    Background: The diagnosis of Attention Deficit Hyperactivity Disorder (ADHD) at a prevalence rate of 5-8% has clear public health and service implications. Studies suggest that certain populations, especially those with lower socio-economic status, are not adequately identified and treated. Evidence-based guidelines aim to standardize practice, but implementing them in low-resource environments can be challenging. To assess compliance, clinical audits for ADHD management have been conducted in higher income countries, but, to our knowledge, there have been no such audits in sub-Saharan Africa. Here we performed a clinical audit of ADHD assessment and treatment and compared compliance between two clinic groups in Cape Town, South Africa. Objectives: The primary aim was to measure compliance in a South African context using the National Institute for Clinical Excellence (NICE) guidelines for ADHD as the gold standard. The secondary aim was to compare compliance and socio-demographics between a 'central’ group (attending a treatment site in an area associated with high socio-economic status) and a 'peripheral’ group (attending in areas associated with low socio-economic status) in Cape Town. Methods: A clinical audit was conducted (March-June 2013) on the case notes for 100 'active’ cases of children or adolescents diagnosed with ADHD. The 'central’ group consisted of patients attending the Red Cross War Memorial Children’s Hospital Neuropsychiatry Clinic. The 'peripheral’ group included cases from community clinics in Retreat, Vanguard, Heideveld, and Kensington. Fifty cases were randomly selected from each group. Data were captured using an audit template derived from NICE guidelines, and a socio-demographic template. Results: Overall, of the 17 audit standards tested none showed 100% compliance. Compliance with four standards was rated 'good’ (>80%): qualified diagnostician (86%), clinician contact with teacher (96%), side effect monitoring (84%), and offering Methylphenidate as first line treatment (80%). Compliance with five standards was 'fair’ (50- 79%): DSM-IV criteria documentation (60%), treatment plan including behavioral or psychological interventions (71%), attempted communication in the patient’s primary language (69%), documentation of the child’s perspective (76%), and monitoring treatment response on standard scales (71%). Compliance with eight standards was 'poor’ (< 0.0001); and treatment response monitoring using standard scales (80% vs. 62%, p = 0.047). Conclusions: Overall, compliance with NICE guidelines for ADHD was low. The central group performed better than the peripheral group in key areas, offering a greater array of treatment options and safer monitoring. We recommend the introduction of structured protocols with re-audit as a tool to improve the quality of service delivery and present an audit checklist to be used in future audit cycles.
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    Open Access
    A comparative risk assessment for South Africa in 2000: Towards promoting health and preventing disease
    (2007) Norman, Rosana; Bradshaw, Debbie; Schneider, Michelle; Joubert, Jane; Groenewald, Pam; Lewin, Simon; Steyn, Krisela; Vos, Theo; Loubscher, Ria; Nannan, Nadine; Nojilana, Beatrice; Pieterse, Desiréé; the South African Comparative Risk Assessment Collaborating Group
    A landmark project of the Medical Research Council, the first South African National Burden of Disease (SA NBD) study, identified the underlying causes of premature mortality and morbidity experienced in South Africa in the year 2000. (1) These estimates were recently revised (2) on the basis of additional data to estimate the disability-adjusted life years (DALYs) for single causes for the first time in South Africa. DALYs are a comprehensive measure of the disease burden combining the years of life lost (YLLs) as a result of premature mortality and years lived with disability (YLDs) related to illness or injury. (3) Compared with the use of mortality as a measure of disease burden, DALYs also capture the contributions of conditions that do not result in large numbers of deaths. For example, mental health disorders have a large disability component relative to the number of deaths. The SA NBD study highlighted the fact that despite levels of uncertainty there is important information to guide public health responses to improve the health of the nation.
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    A comparison of clinical, biochemical, and histological characteristics as well as evaluation of outcomes of patient with mesangiovapillary glomerulonephritis (MCGN) in HIV positive and negative patients at a tertiary hospital in Cape Town, South Africa
    (2023) Sorathia, Shaheed Salim Gulamali; Wearne, Nicola; Jones Erika; Davidson, Bianca
    Background & Aim Mesangiocapillary glomerulonephritis (MCGN) is a common histological pattern of glomerular injury in developing countries. South Africa has the highest proportion of people living with HIV (PWH) and the co-existence of MCGN and HIV may affect kidney prognosis. The aim of this study was to compare the clinical and biochemical features between PWH and HIV-negative individuals with a diagnosis of MCGN and to review kidney function and survival. Materials and Methods A retrospective study was conducted in patients with a biopsy diagnosis of MCGN between January 2010 and December 2017. The following data were collected: age, sex, use of illicit drugs, date of initiation of antiretroviral therapy (ART), blood pressure, presence of oedema, need for kidney replacement therapy, HIV status, CD4 and viral load. Secondary causes were excluded. Kidney outcomes [(serum creatinine, estimated glomerular filtration rate (eGFR), urine protein creatinine ratio (uPCR)] were assessed at 6, 12 and 24 months post biopsy. The composite outcome was defined as a 40% decline in eGFR, progression to end stage kidney disease or death. Results: The study included 116 participants: 27 (23%) were PWH, 89 (77%) were HIV-negative. The median age was 33 years. There were more males in the HIV-negative group [63/89 (71%)]. Oedema was more common in HIV-negative patients [66/86 (77%), p=0.011]. Haemoglobin and albumin were lower in PWH [9.1g/dL vs 11.2 g/dL (p=0.053) and 20 g/L vs 27 g/L, (p=0.053), respectively]. Baseline creatinine, eGFR and uPCR were not different between the groups. However, at 6 and 12 months the creatinine was higher in PWH: 137 μmol/L compared to 97 μmol/L (p=0.028) and 125 μmol/L compared to 87 μmol/L(p=0.023), respectively. uPCR was higher in PWH at 6 and 12 months: 0.63 g/mmol vs 0.075 g/mmol, (p=0.002) and 0.28 g/mmol vs 0.028 g/mmol, (p=0.022), respectively. The composite endpoint was not different between the two groups in the first three years of follow-up.
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    A comparison of physician emigration from Africa to the United States of America between 2005 and 2015
    (2017) Duvivier, Robbert J; Burch, Vanessa C; Boulet, John R
    BACKGROUND: Migration of health professionals has been a cause for global concern, in particular migration from African countries with a high disease burden and already fragile health systems. An estimated one fifth of African-born physicians are working in high-income countries. Lack of good data makes it difficult to determine what constitutes "African" physicians, as most studies do not distinguish between their country of citizenship and country of training. Thus, the real extent of migration from African countries to the United States (US) remains unclear. This paper quantifies where African migrant physicians come from, where they were educated, and how these trends have changed over time. METHODS: We combined data from the Educational Commission for Foreign Medical Graduates with the 2005 and 2015 American Medical Association Physician Masterfiles. Using a repeated cross-sectional study design, we reviewed the available data, including medical school attended, country of medical school, and citizenship when entering medical school. RESULTS: The outflow of African-educated physicians to the US has increased over the past 10 years, from 10 684 in 2005 to 13 584 in 2015 (27.1% increase). This represents 5.9% of all international medical graduates in the US workforce in 2015. The number of African-educated physicians who graduated from medical schools in sub-Saharan countries was 2014 in 2005 and 8150 in 2015 (304.6% increase). We found four distinct categorizations of African-trained physicians migrating to the US: (1) citizens from an African country who attended medical school in their own country (86.2%, n = 11,697); (2) citizens from an African country who attended medical school in another African country (2.3%, n = 317); (3) US citizens who attended medical school in an African country (4.0%, n = 537); (4) citizens from a country outside Africa, and other than the United States, who attended medical school in an African country (7.5%, n = 1013). Overall, six schools in Africa provided half of all African-educated physicians. CONCLUSIONS: The number of African-educated physicians in the US has increased over the past 10 years. We have distinguished four migration patterns, based on citizenship and country of medical school. The majority of African graduates come to the US from relatively few countries, and from a limited number of medical schools. A proportion are not citizens of the country where they attended medical school, highlighting the internationalization of medical education.
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    A comparison of the conditional inference survival forest model to random survival forests based on a simulation study as well as on two applications with time-to-event data
    (2017) Nasejje, Justine B; Mwambi, Henry; Sabur, Natasha F; Lesosky, Maia
    Abstract Background Random survival forest (RSF) models have been identified as alternative methods to the Cox proportional hazards model in analysing time-to-event data. These methods, however, have been criticised for the bias that results from favouring covariates with many split-points and hence conditional inference forests for time-to-event data have been suggested. Conditional inference forests (CIF) are known to correct the bias in RSF models by separating the procedure for the best covariate to split on from that of the best split point search for the selected covariate. Methods In this study, we compare the random survival forest model to the conditional inference model (CIF) using twenty-two simulated time-to-event datasets. We also analysed two real time-to-event datasets. The first dataset is based on the survival of children under-five years of age in Uganda and it consists of categorical covariates with most of them having more than two levels (many split-points). The second dataset is based on the survival of patients with extremely drug resistant tuberculosis (XDR TB) which consists of mainly categorical covariates with two levels (few split-points). Results The study findings indicate that the conditional inference forest model is superior to random survival forest models in analysing time-to-event data that consists of covariates with many split-points based on the values of the bootstrap cross-validated estimates for integrated Brier scores. However, conditional inference forests perform comparably similar to random survival forests models in analysing time-to-event data consisting of covariates with fewer split-points. Conclusion Although survival forests are promising methods in analysing time-to-event data, it is important to identify the best forest model for analysis based on the nature of covariates of the dataset in question.
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    A Decade of Hepatitis C at the UCT/GSH Liver Clinic in the Pre-DAA era
    (2019) Nordien, Rozeena; Sonderup, Mark; Spearman, Wendy
    Background Hepatitis C (HCV) in South Africa is incompletely characterised and understood. Epidemiological and clinical data will better inform our understanding and assist national policy decision making. On the background of more than two decades of clinical challenges in HCV management, the advent of direct acting antivirals (DAA) now makes HCV elimination plausible. To better understand the base from which we come, we elected to review and characterise our HCV experience at Groote Schuur Hospital (GSH) in the Pegylated interferon (Peg-IFN) and Ribavirin (RBV) management era. Methods Patients with chronic HCV attending GSH Liver Clinic from 2002 to 2014, were included, in the analysis. Relevant data were extracted from a registry and existing clinical records accessed. Two brands of Peg-IFN were available and those treated with the first generation add-on protease inhibitor, telaprevir, were included. Results 238 patients were included in the analysis, median age of 47 (IQR 37-58) years, men 60.5%. Men were significantly younger than women, 43.5 (35-52) vs 55 (42-64) years, respectively, p< 0.0001. Ethnically, the majority were white (55.9%) or mixed-ancestry (21.8%), 16.4% were HIV co-infected, 3.7% hepatitis B (HBV) co-infected and 0.4% triple infected with HCV, HBV and HIV. The most likely mode of HCV acquisition was blood/blood product exposure prior to 1992 (32.8%) and injecting drug use (IDU) 17.6%, while 30.3%, had no clear risk factor identifiable. Genotypes (GT) 1 to 5 were observed with GT-1 (34.9%) predominating. In those biopsied, (n=90), 30% ≥F3 fibrosis, with 15.6% cirrhotic. With IL28B polymorphisms, heterozygous CT (23.9%) and CC genotype (15.5%), were most frequent. 32.6% accessed Peg-IFN/Ribavirin-based therapy, 6.5% (n=5) with add-on telaprevir. GT-1 (35.1%) was most prevalent in the treatment group, followed by GT-3 (26%) and GT-5 (18.2%); 10% were HIV co-infected. Overall SVR rate was 75.3% with 37% of GT-1 not achieving SVR; 49.4% experienced adverse events including cytopaenias (32.5%) and depression (15.6%) with 15.6% requiring erythropoietin for anaemia and 15.6% GM-CSF for neutropaenia. Conclusion HCV patients in the Peg-IFN/Ribavirin management era typified the epidemiology of HCV. GT distribution was pangenotypic and treatment outcomes were encouraging despite treatment challenges. Patient selection, IL28B and sensible cytopaenia support, likely accounted for this. However numbers treated were limited and the DAA era of therapy allows for a rapid expansion of therapy with now growing numbers of patients and a changing local epidemiology.
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    Open Access
    A decade of tobacco control: The South African case of politics, health policy, health promotion and behaviour change
    (2013) Reddy, Priscilla; James, Shamagonam; Sewpaul, Ronel; Yach, Derek; Resnicow, Ken; Sifunda, Sibusiso; Mthembu, Zanele; Mbewu, Anthony
    BACKGROUND: The South African (SA) government has implemented comprehensive tobacco control measures in line with the requirements of the Framework Convention on Tobacco Control. The effect of these measures on smoking prevalence and smoking-related attitudes, particularly among young people, is largely unknown. OBJECTIVE: To describe the impact of a comprehensive health promotion approach to tobacco control amongst SA school learners. METHODS: Four successive cross-sectional Global Youth Tobacco Surveys (GYTSs) were conducted in 1999, 2002, 2008 and 2011 among nationally representative samples of SA grades 8 - 10 school learners. We assessed the prevalence of current smoking (having smoked a cigarette on ≥1 day in the 30 days preceding the survey) and smoking-related attitudes and behaviours. RESULTS: Over the 12-year survey period current smoking among learners declined from 23.0% (1999) to 16.9% (2011) - a 26.5% reduction. Reductions in smoking prevalence were less pronounced amongst girls and amongst black learners. We observed an increase in smoking prevalence amongst learners between 2008 and 2011. Smoking-related attitudes and behaviours showed favourable changes over the survey period. CONCLUSION: These surveys demonstrate that the comprehensive and inter-sectorial tobacco control health promotion strategies implemented in SA have led to a gradual reduction in cigarette use amongst school learners. Of concern, however, are the smaller reductions in smoking prevalence amongst girls and black learners and an increase in smoking prevalence from 2008 to 2011. Additional efforts, especially for girls, are needed to ensure continued reduction in smoking prevalence amongst SA youth.
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    A description of the pharmacokinetics of first line anti-tuberculosis drugs and adjunctive corticosteroid therapy in the pericardial compartment and their effect on cytokine profiles in the pericardial compartment of patients with tuberculous pericarditis
    (2025) Shenje, Justin Tapiwa; Ross, Ian
    Tuberculous pericarditis is caused by Mycobacterium tuberculosis infection of the pericardium, which is associated with a higher mortality, compared with pulmonary tuberculosis. Constrictive pericarditis, a significant complication of tuberculous pericarditis, contributes to this elevated mortality. Adjunctive corticosteroid therapy with prednisolone, has been shown to reduce the incidence of constrictive pericarditis by more than 50%. However, this is associated with significant side effects, especially in patients with HIV co-infection. Constrictive pericarditis is only partially responsible for this increased mortality, whereas other factors including delayed diagnosis of tuberculosis, cardiac complications for example, pericardial tamponade and poor pericardial exposure of anti-TB drugs also likely contribute. The pharmacokinetics of anti-tuberculous (TB) drugs within the pericardial space remain poorly understood and until now have relied on studies of pulmonary tuberculosis. While adjunctive corticosteroids have been shown to be beneficial, there are no available data on the pharmacokinetics of prednisolone in the pericardium, and uncertainty remains as to whether an empiric dose of 120 mg prednisolone is the optimal dose for reducing the incidence of constrictive pericarditis or whether it is detectable at the site of infection, to exert its pharmacodynamic effect. Combining anti-TB treatment and high doses of prednisolone are likely to have a profound effect on the immune response, therapeutic effect and cortisol milieu in the pericardium. I was therefore interested in investigating the impact of this therapeutic combination, through direct sampling of the pericardial fluid in patients with tuberculous pericarditis. Methods: A total of 16 patients with newly diagnosed tuberculous pericarditis and a pericardial effusion requiring pericardial aspiration, were enrolled into the study. The patients were randomly assigned to 120 mg of prednisolone or matching placebo and were simultaneously started on first line World Health Organization (WHO) anti-tuberculosis treatment, namely, rifampicin, isoniazid, ethambutol and pyrazinamide. Intensive pharmacokinetic samples were collected at the following timepoints, just before administration of the anti-tuberculosis treatment and prednisolone or placebo and at 0.5 hour, 1 hour, 2 hour, 3 hour, 5 hour, 8 hour and 24 hour intervals thereafter for the first 24 hours. Intensive pharmacokinetic samples were collected from plasma, pericardial fluid and saliva. The pharmacokinetics of rifampicin, isoniazid, ethambutol and pyrazinamide in the pericardium were described so as to assess the adequacy of conventional doses of the WHO first line anti-TB treatment regimen. The study also described the pharmacokinetics of 120 mg of prednisolone and evaluated its effect on endogenous corticosteroids and cytokines. Furthermore, the study compared the immunological response to tuberculous pericarditis in plasma and pericardium. Results: While pericardial drug exposures to isoniazid and pyrazinamide were comparable to those of plasma, there was a reduction in rifampicin and ethambutol exposure in the pericardium, which were 20%; (p<0.0010) and 55%; (p<0.0010) of their respective plasma drug exposures. The median pericardial rifampicin concentration was 0.125 mg/L, which was lower than the reference minimum inhibitory concentration (MIC) for Mycobacterium tuberculosis isolates, which was 0.208 mg/L (p=0.0010). The pharmacokinetic profile of prednisolone in the pericardium was similar to that of the plasma, but there was a 1.60 hours delay (p=0.0320) in time to maximum concentration (Tmax) in the pericardial space. Adjunctive corticosteroid therapy administered as a single dose of 120 mg of prednisolone, was associated with 83% reduction in median plasma interleukin-6 (p=0.0360), a 50% reduction in median plasma interleukin-8 (p=0.0300) and a 50% reduction in median pericardial interleukin-8 (p=0.0400). Prior to administration of glucocorticoids, the pericardial cortisol/ cortisone ratio was twice that of plasma (p=0.0050). A similar elevation of the cortisol/ cortisone ratio at the site of infection has previously been described in the bronchial lavage fluid of patients with pulmonary tuberculosis. Among those participants who did not receive glucocorticoids, pericardial cytokine interferon-gama, tumour necrosis-alpha, interleukin-6, interleukin-8, interleukin-10, and interferon gamma-induced protein-10 concentration increases were multiples fold higher than their corresponding plasma concentrations, (p=0.0011), (p=0.0043), (p=0.0009), (p=0.0001), (p=0.0054) and (p=0.0031), respectively. Conclusion: By directly sampling the pericardial fluid among patients with tuberculous pericarditis, I was able to gain novel insights, which have never previously been described. The reduced pericardial rifampicin and ethambutol exposures, below the required minimum inhibitory concentrations in the pericardial space, are of great concern, particularly, considering the relative importance of rifampicin in the treatment of drug sensitive tuberculosis. This warrants a revision of the dosing strategy, or a review of therapeutic regimen used in tuberculous pericarditis, to enhance efficacy. Prednisolone administered at a dose of 120 mg daily orally is detectable with high exposure in the pericardium and may explain the beneficial effect observed in tuberculous pericarditis among HIV negative individuals, through its alteration in the cytokine milieu, and lower propensity to developing constrictive pericarditis. Additionally, the raised cortisol/ cortisone ratio at the site of infection, the pericardium, compared with other matrices especially plasma may indicate an immunomodulatory role either to dampen an excessive or evoke an immunological response.
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    A descriptive study of the type 2 diabetic population with hypertriglyceridemia of more than 2.5 mmol/l at presentation with subsequent analysis of their baseline and follow up variables
    (2023) Vermooten, Barbara; Blom, Dirk
    Background Type 2 diabetes mellitus and the dyslipidaemia that often accompanies it are major risk factors for atherosclerotic cardiovascular disease. Elevated triglycerides mark the accumulation of atherogenic remnant lipoproteins. Because there is little South African data on hypertriglyceridaemia in diabetes we retrospectively reviewed baseline and follow-up data of patients attending a specialized lipid clinic. Aim of the study The primary aim of this study is to describe biochemical and demographic variations of a diabetic population with hypertriglyceridemia and to further investigate whether there are correlations between glycemic control, lipid modifying therapy and hypoglycemic therapy with lipid outcomes, specifically LDL cholesterol, remnant cholesterol, triglycerides, and HDL-C. Methods We reviewed the medical records of 100 diabetic patients with hypertriglyceridemia of >2.5mmol/L who attended the Groote Schuur Hospital Lipid clinic for at least two years. The patients were randomly selected from the Lipidology database, and selection was made based on inclusion criteria for this study. We documented four six-monthly follow-up visits and documented the visit with the lowest recorded triglyceride levels if it was outside the two-year follow-up. Results The study population was predominantly (63%) female with a mean (SD) age at presentation of 50.87 (10.44) years. Obesity (BMI >30 kg/m²) was highly prevalent (66.3%) and diabetes was generally poorly controlled (76.16% patients had a HbA1C >7%). Baseline triglycerides ranged from 2.6mmol/L to 63.3mmol/L with a median and mean (SD) of 4.64 mmol/L and 10.47 (12.57) mmol/L, respectively. Baseline agarose electrophoresis patterns were: 0% type I, 0% type IIA, 51.4% type IIB, 10.3% type III, 18.7% type IV and 19.6% type V. LDL particle size determined by acrylamide gradient gel electrophoresis was intermediate or small in 61 of 64 (95%%) of patients with visible LDL. At baseline calculated mean (SD) remnant cholesterol (48 patients) was 1.55 (0.24) mmol/L, ranging from 1.1mmol/L to 2mmol/L. Triglycerides and calculated remnant cholesterol were strongly correlated (r2=0.9395, p=0.000). There was no correlation between baseline TG and HDL-C, baseline BMI and baseline waist circumference (waist/hip ratio could have possibly corrected for different anthropometry), but there was a positive correlation between triglycerides and alcohol intake, (r2=0.224, P=0.012). There was no correlation between baseline triglycerides and HbA1C (p=0.8423) or fasting glucose (p=0.0857). The change in total triglycerides from initial presentation to the follow-up visit with the lowest documented value was a mean (SD) decrease of 2.91 (4.98) mmol/L, ranging from either no change to a decrease of 32.68mmol/L. The mean (SD) reduction in HbA1C was 0.94 (1.64) % ranging from an increase of 1.7% to a decrease of 7.8%. Fibrates were initiated in 43% of patients. Patients prescribed fibrates had higher mean (SD) baseline TG levels of 18.56(15.48) mmol/L, compared to levels of 4.11(1.85) mmol/L in patients who were not prescribed a fibrate. At baseline mean (SD) TC values were 8.33 (3.18). The mean (SD) LDLC at baseline was 4.26 (1.45) mmol/L ranging from 0.5 to 7.6 mmol/L. Only 4.1% of all patients with a calculable LDL-C achieved values below 1.8mmol/L during follow-up. Conclusions In this study diabetic patients with elevated triglycerides who attended a specialist lipid clinic were frequently obese and often had poorly controlled diabetes. Although dyslipidaemia and glycaemia improved following intensification of therapy most patients did not reach their treatment goals. Our study highlights the heterogeneity of hypertriglyceridaemia, the difficulties of achieving good metabolic control, and the need for ongoing follow-up as severe hypertriglyceridaemia relapses readily.
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    A descriptive study of the use of cardiac point of care ultrasound (PoCUS) in public emergency centres in Cape Town
    (2021) Ganas, Ushira; Malan, Jacques J; Bruijns, Stevan R
    Background Cardiac point of care ultrasound (PoCUS) has evolved into an important diagnostic tool in the daily practice of emergency medicine. Its use has been advocated internationally, but its limitations have also been emphasised. The indications for cardiac PoCUS vary somewhat in different parts of the world, and training programs may also differ. We set out to describe the self-reported indications and imaging windows used at a selection of secondary-level, public hospital emergency centres in Cape Town. Methods A descriptive study with prospective data collection from the emergency centres of Mitchells Plain District, Victoria and New Somerset Hospitals was used. Data were collected over a three-month period, by all formally consented providers who have completed a basic emergency ultrasound course, using a purpose-designed data collection tool for all cardiac PoCUS scans. The study was approved the University of Cape Town's Human Research Ethics Committee (581/2017). Results We recruited 15 PoCUS providers who recorded 267 data entries over the 3-month study period. Seventeen surveys were excluded leaving 250 for analysis. The most common indication for cardiac PoCUS was electrocardiogram abnormalities,27% (n= 112); dyspnoea,25% (n= 102); chest pain,16%(n=65); cardiomegaly on chest xray,12%(n=51); new murmur,6%(n=23); and chest trauma,5%(n=22). Other indications made up the remaining 10%(n=40). Parasternal long and short axis were the predominantly used views. Conclusion The results of the study suggest that cardiac PoCUS is used for a wide range of indications which are recommended in training guidelines. However, some indications are outliers but may be useful in low-middle income settings. Further research needs to be done to ascertain the extent of the use of cardiac PoCUS, and possibly the need for a more comprehensive training program with adequate training in these clinical conditions, to ensure safe practice.
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    A determination of the prevalence of palliative care patients admitted to the Groote Schuur Hospital Emergency Centre and their Presenting Complaints
    (2022) Govender, Radha; Krause, René; Szymanski, Patryk
    Background: The Emergency Centre is often an entry point to health services and is, therefore, well positioned to identify patients with palliative care needs. It is also the place of care sought by the families of palliative care patients when their loved ones are seriously ill or terminal. It becomes important to understand the numbers of palliative care patients presenting to Emergency Centres and the reasons why they present there, in order to strengthen the care provided to these patients in the Emergency Centre. Objectives: This study aimed to determine the prevalence of palliative care patients in a tertiary academic hospital Medical Emergency Centre, and to establish their presenting complaints. Method: The study was an exploratory and descriptive quantitative study based on a review of folders of admitted patients. Non-random sampling with a convenience sampling method was used. Data collection was carried out from 01-11 August 2019. Folders of patients admitted to the Emergency Centre were reviewed, data was collected onto an excel workbook, and analysed. Data collected included patient demographics, symptoms, diagnoses, reasons for presentation, and previous history of palliative care services. Results: Over the data collection period, 383 patients were admitted to the Emergency Centre. 124 of these patients were found to have palliative care needs. Palliative care prevalence over the measured period in the Emergency Centre was therefore 32.4%. Forty-eight percent (48%) of the palliative care patients were male, 52% were female. The most frequent reasons for admission to the Emergency Centre were pain (14% of patients), shortness of breath (7%), loss of/reduced levels of consciousness (6%), and heart disease (5%). 35% of patients presented during business hours (8am-4pm), 62% presented after hours (4pm- 8am). The most frequent reason for admission after hours was pain (18% of palliative care patients admitted after hours). There were no pain- related reasons for admission during business hours. Shortness of breath and heart disease were the most frequent reasons for admission during business hours – forming 6.8% each of all palliative care related business hour admissions. The most frequent symptoms noted for palliative care patients were pain (32.0%), loss of/reduced level of consciousness (30.6%), shortness of breath (24.2%). The most common palliative care related diagnoses were heart/vascular disease (29,0%), cancer progressive and/or metastatic (26.6%) and neurological disease/stroke (19.4%). The top 3 diagnoses in both females and males were hypertension, heart disease and cancer. The most frequent symptom presented by cancer patients was pain. Hospice services are available in the vast majority (96%) of the suburbs in which the patients reside. Only 5.6% of the palliative care patients had been referred to palliative care services. Conclusion: The Emergency Centre is an important catchment zone for the identification and management of palliative patients. Understanding the expected volume of palliative care patients in an Emergency Centre will allow staff to plan for their special needs. The prevalence of palliative care patients presenting to an Emergency Centre is 32.4%. To better support palliative care patients, it is important to understand why patients with palliative care needs present to an Emergency Centre. Pain, shortness of breath and loss of/reduced levels of consciousness are driving patients to the Emergency Centre. While South Africa has a preliminary level of integration of palliative care services with health services, palliative care services are not available to patients and their families on weekends and after hours. Until this has been remedied and other sources of care are in place, Emergency Centres remain an important site of access to care for distressed patients. This therefore requires that a palliative care approach be followed to meet patient needs, and that palliative care training is prioritised for healthcare professionals working in an Emergency Centre.
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    A mixed method study of the factors influencing the validity of medical and medication histories obtained from potential healthy adult clinical trial participants
    (2019) Ltayef, Hanan; Allen, Elizabeth; Annemie, Stewart
    Background: The medical histories of patients are data picked up by a doctor by making inquiries of the patient and of other individuals who know the individual and can give a reasonable response. In clinical trials, obtaining an accurate medical and treatment history is also an important factor in establishing whether or not a person is an eligible participant, and thereafter supports the assessment of any change in health during the trial, for example, the assessment of adverse events (AEs). Study objectives: To understand discrepancies between the medical histories from online self-reports, electronic medical records, and in-depth interviews of those applying to be part of an adult volunteer database for clinical trials; explore ways of engaging with potential volunteers, such that self-reported medical histories are as comprehensive as possible; explore the feasibility of accessing electronic records for those responding to advertisements. Methodology: This study was designed as mixed methods, with sequential explanatory design collecting quantitative and qualitative data and nested in an existing adult volunteer database. people from the Cape Town community were invited to join the database, in response to an advertisement and through a link to the database website; particularly those who were potentially eligible for a typical healthy volunteer trial, and who reported different information to that obtained from the electronic records. Results: 38 people responded to the online questionnaire, the majority being female. According to the online self-report questionnaire, ten people (10/38; 26.3%) had chronic medical conditions; mostly HIV (7/10; 70%). We accessed the Western Cape electronic medical records for only 8/38 (21%). Comparing the online questionnaire with the medical records, it was found that 25% of respondents had no difference in information. 10/38 people (26.3%) agreed to participate and were available for an in-depth interview. The main findings were: 1) a very low response rate to the advertisement, 2) people in this community are willing to consider taking part in clinical research, but have different understandings of what that means, 3) there were discrepancies between online self-reported health and medication data and what was found in a pilot database of electronic public health records and during a face-to-face interview, 4) the reason for these differences, as perceived by participants, included forgetting some information, feeling it was not relevant or important to report because of the attributes of the online questionnaire and 5) these participants had no concerns about us accessing their electronic medical records. Conclusion: Our study provides some evidence for optimal places to advertise for an adult volunteer database, and the appropriate wording and format of both the advertisements and the online questionnaire. More efforts are needed to educate the general public on understand the meaning of clinical trials. Electronic medical records may be accessed to help understand potential participants’ eligibility for trials, but the feasibility of accessing such data timeously may need further negotiation.
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    A novel cash-plus intervention to safeguard sexual reproductive health and HIV vulnerabilities in young women in Cape Town, South Africa
    (2023) Naledi Tracey, Noncayana; Bekker, Linda-Gail; London, Leslie
    Background Cash plus interventions augment cash transfers with other empowering interventions to influence behaviours. This research assesses the Women of Worth (WoW) program and evaluates the effectiveness of a cash transfer (CT) of ZAR300 ($22USD22) conditional on attending 12-session customised empowerment interventions to improve SRH/HIV outcomes in young women (19-24yrs) in Cape Town, South Africa. Methods A multiphase, mixed-methods, experimental study targeting 10 000 Participants in two subdistricts was conducted. Participants were randomised 1:1 to receive the interventions with CT ("cash + care" or C+C) or without CT (“Care”). Phase 1a piloted the interventions, Phase 1b implemented an adapted intervention, and Phase 2 was an open label C+C only scale up demonstration phase. Logistic regression models were fitted with subject-specific random mixed effects, to estimate changes in self-reported HIV, behavioural and structural SRH risks from baseline to (a) end of WoW and (b) follow up (6-30months post-exposure) irrespective of WoW completion. Mixed research methods were used to optimise engagement, evaluate implementation fidelity and determine the pathways of effectiveness for the interventions. Results The Women of Worth empowerment programme was implemented with adequate fidelity however adaptative research methods were essential for ensuring a sustained programme. 8765 (87,7%) of the 9995 WoW initiators were evaluated with 904 (10,3%); 4212 (48,1%) and 3649 (41,6%) women in Phases 1a, 1b and 2 respectively. In Phase 1a & 1b, participants in the “C+C” group were 60 times (OR 60.37; 95%CI: 17.32; 210.50.p
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    A pharmacometric approach to optimal use of second line drugs for multidrug-resistant tuberculosis
    (2023) Court, Richard Gray; Mcilleron, Helen; Maartens, Gary
    Until the recent introduction of short course regimens, treatment regimens for multidrug resistant TB (MDR-TB) were long and toxic. Consequently, only approximately half of MDRTB patients completed their treatment. TB dosing guidelines have historically been unrefined with little consideration for pharmacokinetic/pharmacodynamic relationships. Large knowledge gaps therefore exist in the understanding of pharmacokinetic/pharmacodynamic relationships for both efficacy and toxicity in MDR-TB. My PhD used clinical pharmacology approaches to improve the understanding of drug exposures, toxicity, and exposure-toxicity relationships during the first 12 weeks of MDR-TB therapy. Aims and methods 1. Using non-compartmental analyses, describe the pharmacokinetics of cycloserine and, using regression modelling, explore the association of covariates with cycloserine exposure. 2. Using validated screening tools, describe the incidence of neuropsychiatric toxicity in MDR-TB patients, and explore associations with cycloserine pharmacokinetics. 3. Using a validated pain-rating scale in a crossover study design, investigate whether the addition of a local anaesthetic reduces kanamycin-related injection pain, and explore effects on kanamycin pharmacokinetics. 4. Using geometric mean ratios, compare the exposures of crushed versus whole formulations of pyrazinamide, moxifloxacin, ethionamide, ethambutol, cycloserine, and isoniazid. Results and conclusions We found no measurable terizidone in plasma supporting the hypothesis that terizidone is hydrolysed pre-systemically to cycloserine. The cycloserine time-concentration profile supports once daily dosing of terizidone. We describe a high incidence of peripheral neuropathy in MDR-TB patients with both cycloserine clearance and high-dose pyridoxine significantly associated with neuropathy on multivariate analysis. The addition of a local anaesthetic reduced the pain experienced by MDR-TB patients in the first 15 minutes post intramuscular administration of kanamycin, which could improve adherence to MDR-TB treatment. We also found the bioavailability of crushed isoniazid to be approximately 42% less than the whole tablet formulation, and therefore recommend that the crushing of isoniazid be avoided. Although some recent treatment advances have improved MDR-TB outcomes, enhancing the understanding of drugs used to treat MDR-TB, which continues to have an unacceptably high mortality and treatment-related morbidity, is a public health priority. This thesis comprises four peer-reviewed publications, all of which made a pragmatic contribution to the fight against MDR-TB.
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    A proposal for the eradication of rheumatic fever in our lifetime
    (2006) Mayosi, Bongani M
    The Pan African Society of Cardiology (PASCAR) convened the 1st All Africa Workshop on Rheumatic Fever (RF) and Rheumatic Heart Disease (RHD) on 15 - 16 October 2005 at the Champagne Sports Resort, Drakensberg, South Africa. The purpose of the Workshop was to formulate an action plan for the prevention of RF and RHD in Africa. The gathering was a response to the new guideline on the control of RF and RHD by the World Health Organization (WHO) in 2004.1 The meeting (and this supplement) was made possible by the generous sponsorship of the national Department of Health of South Africa, the Medical Research Council of South Africa, the WHO Regional Office for Africa (WHO-AFRO) and the World Heart Federation, and endorsed by the Heart Foundation of South Africa, the Paediatric Cardiac Society of South Africa, and the South African Heart Association. The other organisations represented at the meeting included the Africa Heart Network, the Nigerian Heart Foundation, and academics from the universities of Alexandria, Cape Town, Ghana, Ibadan, KwaZulu-Natal, Libreville, Limpopo, Nairobi, Pretoria, and Eduardo Mondlane University.
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    A Radiological study of the Right Lung
    (1943) Oosthuizen, Sarel Francois
    The purpose of this thesis is to illustrate the author's observations on radiological investigations of the right lung both in the living body and at post-mortem, and to describe certain aspects of anatomical, clinical, pathological and radiological interest.
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    A randomised controlled trial of N-acetylcysteine in the management of anti-tuberculosis drug-induced liver injury
    (2023) Moosa, Muhammed; Cohen, Karen; Maartens Gary
    Background: Liver injury is the most common severe adverse effect of first-line anti-tuberculosis therapy (ATT). Nacetylcysteine (NAC) has efficacy in patients with paracetamol toxicity, and may be of benefit in liver injury due to other causes, such as ATT-induced liver injury (AT-DILI). Rechallenge of first line ATT after liver injury is usually attempted and may result in recurrence of liver injury. Alanine transaminase (ALT) is the biomarker currently used in AT-DILI diagnosis. MicroRNA-122 (miR-122) is a sensitive biomarker for liver injury due to paracetamol, but data on utility as a biomarker for ATDILI are limited. Methods: We conducted a randomized double-blind placebo-controlled trial of intravenous NAC in adult hospitalized participants with AT-DILI. Primary endpoint was time to ALT < 100 U/L; secondary endpoints included length of hospital stay and 8-week mortality. We described outcomes of ATT rechallenge following AT-DILI. We quantified miR-122 and ALT concentrations before and after infusion of NAC/placebo, and explored the effect of NAC on miR-122. Results We enrolled 102 participants with AT-DILI, 53 randomized to NAC and 49 to placebo. Mean age was 38 (SD±10) years, 58 (57%) were female and 89 (87%) were HIV positive. Median time to ALT
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    A retrospective review of lung disease in adolescents living with human immunodeficiency syndrome
    (2025) Naicker, Janani; Van Zyl-Smit, Richard; Perumal, Rubeshan; Vanker, Aneesa
    Chronic lung disease (CLD) is common in adolescents living with Human Immunodeficiency Virus (ALHIV), many of whom have survived early childhood respiratory infections and immune dysregulation. Little is known about the characteristics of ALHIV with CLD. Understanding the characteristics of this population is key to guiding service design, informing preventative strategies, and identifying tailored therapeutic interventions for preserving lung function and optimizing respiratory health. Methods: We retrospectively reviewed the clinical records of a historical cohort of adolescents aged 12 years to 20 years, diagnosed with vertically transmitted HIV and presenting with chronic lung disease to the Adolescent Respiratory Clinic of Groote Schuur Hospital between 1 January 2015, and 1 January 2023. Demographic data, details on HIV diagnosis, treatment history, lung function data, radiological data, clinical history and examination data, and microbiological data were analysed. Results: Seventeen patient records were reviewed. The median age at first visit was 16.9 years (interquartile range (IQR)15.2 to 18.7), and 58.9% (10/17) were female. The median age at HIV diagnosis was 1.1 years (IQR 1- 2), with a median duration of ART treatment of 13.2 years (IQR,8.6- 15.6), reflecting early HIV diagnosis and treatment initiation. The median CD4 nadir was 243 cells/mm3 (IQR 140- 516) and 16/17 patients had more than two prior episodes of pulmonary tuberculosis (PTB). Growth stunting was a common feature with a median BMI 17.7 kg/m2 (IQR 16.4- 19.8) and 16 /17 participants plotting below the 50th population centile of height-for-age. Radiological evidence of bilateral lung disease with bronchiectasis and cavitation was ubiquitous. Haemophilus influenzae was isolated in 12/17 (70.6%) patients and Methicillin-resistant staphylococcus aureus (MRSA) in 2/17 (11.7%) patients). The median FVC as a percentage of predicted values was 51.7% (IQR, 41.1- 60.8) and the median pre- bronchodilator FEV1/FVC ratio was 65%, (IQR of 57.8 to 74.3). indicating mixed spirometric defects. There was no significant bronchodilator response in any of the participants. Conclusion: Among ALHIV with CLD, there was a high prevalence of both airway and parenchymal lung disease, as well as severe growth impairment. Prior PTB was a common respiratory insult, despite early ART initiation. More needs to be done to prevent PTB, reduce the burden of recurrent respiratory infections, and to preserve long-term respiratory health in this vulnerable population. What the study adds: This study characterised a cohort of adolescents living with HIV and chronic lung disease in South Africa. Prior tuberculosis was common, and extensive bilateral structural lung abnormalities were universal. A significant proportion of the cohort exhibited severe growth impairment. Taken together, this study identifies ALHIV and CLD as a population with a high burden of respiratory deficits. Evidence-based secondary prevention and therapeutic strategies are needed to ensure the long-term preservation of lung function in these individuals.