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- ItemOpen AccessA 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 ABACKGROUND 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.
- ItemOpen AccessA 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 JBackground: 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.
- ItemOpen AccessA 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 GroupA 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.
- ItemOpen AccessA 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, BiancaBackground & 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.
- ItemOpen AccessA 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 RBACKGROUND: 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.
- ItemOpen AccessA 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, MaiaAbstract 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.
- ItemOpen AccessA Decade of Hepatitis C at the UCT/GSH Liver Clinic in the Pre-DAA era(2019) Nordien, Rozeena; Sonderup, Mark; Spearman, WendyBackground 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.
- ItemOpen AccessA 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, AnthonyBACKGROUND: 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.
- ItemOpen AccessA 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 RBackground 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.
- ItemOpen AccessA 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, PatrykBackground: 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.
- ItemOpen AccessA 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, StewartBackground: 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.
- ItemOpen AccessA molecular investigation of Waardenburg syndrome in Southern Africa(1994) Butt, Jennifer Leigh
- ItemOpen AccessA 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, LeslieBackground 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
- ItemOpen AccessA pharmacometric approach to optimal use of second line drugs for multidrug-resistant tuberculosis(2023) Court, Richard Gray; Mcilleron, Helen; Maartens, GaryUntil 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.
- ItemOpen AccessA proposal for the eradication of rheumatic fever in our lifetime(2006) Mayosi, Bongani MThe 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.
- ItemOpen AccessA Radiological study of the Right Lung(1943) Oosthuizen, Sarel FrancoisThe 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.
- ItemOpen AccessA randomised controlled trial of N-acetylcysteine in the management of anti-tuberculosis drug-induced liver injury(2023) Moosa, Muhammed; Cohen, Karen; Maartens GaryBackground: 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
- ItemOpen AccessA retrospective review with prospective follow up of renal function, blood pressure and proteinuria post living donor nephrectomy at Groote Schuur Hospital, Cape Town South Africa(2020) Murugan, Ashley; Dave, NicolaIntroduction: Renal transplantation is the treatment of choice for patients with end stage renal disease [ESRD]. An increased risk of ESRD has been demonstrated when comparing donors to age matched healthy non-donors. There are no outcome data in Africa on long term donor renal function or mortality. Therefore, this study aimed to assess long term health complications in the living donor population and evaluate risk factors associated with poor health outcomes of the donors. Methods: This was a retrospective review with prospective follow up of persons undergoing living related donor nephrectomy for renal transplantation, at Groote Schuur Hospital (GSH) from January 2005 to November 2017. We retrospectively analysed baseline demographics, clinical information including blood pressure and renal function (creatinine, eGFR and proteinuria) and compared them with follow up blood pressure and renal function. Results: The majority of the donors were of mixed ancestry 94/154(61%) and 1st degree relatives 111/154 (72%) of which 63/111 (56.8%) donors were siblings. Hypertension developed in 16/31 (51.6%) donors at follow-up. Those developing hypertension had a higher mean baseline blood pressure (systolic blood pressure 139±11.3 mmHg and diastolic blood pressure 85.5±7.3 mmHg). 21/49(42.9%) developed chronic kidney disease [CKD], of which, 16 donors had an eGFR < 60 ml/min/1.73m2 . In those that developed CKD there was a higher percentage of males (p=0.018) and they were older (p=0.048) at baseline. Baseline systolic and diastolic blood pressures was not statistically different in those that developed CKD. 3/31(9.6%) donors developed diabetes. Conclusions: In South Africa, CKD is on the rise and the need for kidney donors for patients with ESRD is therefore also increasing. This study demonstrates that our living donors are at increased risk of CKD and hypertension and therefore need to be followed up more rigorously.
- ItemOpen AccessA retrospective study of patients with biologics treatment at Groote Schuur and Red Cross Children's War Memorial Hospitals(2020) Ahmed, Mohammed Awad Eltoum; Hodkinson, Bridget; Gcelu, AyandaIntroduction. The high cost and concern of adverse events, particularly infections, limit the use of biologic disease-modifying anti-rheumatic (bDMARD) therapies. We undertook this retrospective study to document their use for immune-mediated diseases (IMDs) and explore the efficacy, safety, adherence and screening practices prior to initiating bDMARDs in a tertiary referral hospital. Methods. A folder review of all adult and paediatric patients treated for IMDs with bDMARDs at Groote Schuur and Red Cross Hospitals between January 2013 and December 2019. Clinico-demographic particulars, details of bDMARD therapy, and adverse events were collated. Changes in disease activity were measured by diseasespecific tools at 6, 12, 24-months and at the last available visit, and patient adherence to bDMARDs was explored by folder and pharmacy record review. Results. We studied 151 folders, with 182 bDMARDs uses (29 patients used more than 1 bDMARD). Patients were from rheumatology (n= 38: 13 rheumatoid arthritis; 10 spondyloarthritis, 5 Systemic Lupus Erythematosus (SLE) , 5 inflammatory myositis and 5 other conditions); gastroenterology (n=31; 26 Crohn`s and 5 Ulcerative Colitis), dermatology (n=9; psoriasis), neurology (n=4, ophthalmology (n= 25; 6 scleritis, 18 uveitis, 1 optic neuritis), and paediatrics (n= 45, 26 juvenile idiopathic arthritis , 12 SLE, 7 other conditions). The bDMARDs used were TNF inhibitors (112), rituximab (55), tocilizumab (10), anakinra (3), abatacept (1), and tofacitinib (1). The vast majority of patients had an excellent response and were in low disease activity or remission at their last available visit. Adverse events included severe infection (4), tuberculosis (TB) (2), mild infection (4), severe allergic reaction (3), mild skin reaction (14), elevated liver enzymes (2), and worsening interstitial lung disease ILD (1). bDMARD Therapy was discontinued in 18 patients, most commonly due to adverse reaction (9), lack of response (3), poor adherence (2), or remission (1). bDMARD Therapy was changed to alternative therapy in 29 patients, most commonly because of poor response (14), or adverse effects (9) or poor adherence (3). Poor adherence or patients lost to follow-up was noted in 18/182 (9.9%). Complete latent TB infection screening with chest x-ray and TB skin test was performed in only 55 (36.4 %) but INH prophylaxis was given to 51/88 (57.9%) of patients prescribed TNFi therapy. Hepatitis B screening performed in 93 (61.6 %) patients, but most patients (72.2 %) were not tested for Hepatitis B core ab. Hepatitis C screening was performed in 81 (53.6 %) patients. Only 88 (58.3%) patients had a recent HIV test. The majority (17.2%) received the influenza vaccine, but only 24 (15.8 %) received pneumococcal vaccination. Discussion and Conclusion. bDMARD therapy was an effective treatment, and the most common adverse effect was infection (7.2%), with 2 TB infections. Vaccination and screening for TB, viral hepatitis and HIV was suboptimal. Of concern, poor adherence to bDMARDs was frequently encountered.
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