1. Academic Wits Research Publications (Faculties submissions)
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Item Clinical characteristics and one-year all-cause mortality outcomes in Africans with dilated cardiomyopathy(Elsevier, 2023) Tsabedze, Nqoba; Mpanya, Dineo; Bailly, Claude; Nel, Samantha; Grinter, Sacha; Ramsay, Michele; Krause, Amanda; Wells, Quinn; Manga, PravinAims: Dilated cardiomyopathy (DCM) is a common cause of heart failure in sub-Saharan Africa (SSA). The affected individuals present with new-onset heart failure with reduced ejection fraction and no identifiable primary or secondary aetiology. We aim to describe the clinical characteristics of participants with heart failure of unknown origin. Methods: We screened 161 participants with heart failure of unknown origin and prospectively excluded primary and secondary causes of DCM. All study participants were subjected to laboratory biochemical testing, echocardiography, cardiovascular magnetic resonance (CMR) imaging and invasive coronary angiography. Results: The study comprised 93 participants with a mean age of 47.5 SD 13.1 years. Forty-six (56.1%) participants had evidence of late gadolinium enhancement (LGE) on imaging, and LGE was visualised in the mid wall in 28 (61.0%) of these participants. After a median duration of 13.4 months [interquartile range (IQR): 8.8–28.9 months], 18 (19%) participants died. Non-survivors had a higher median left atrial volume index (44.9 mL/m2 (IQR: 34.4–58.7) compared to survivors [32.9 mL/m2 (IQR: 24.5–47.0), p = 0.017)]. The rate of all-cause rehospitalisation was 29.3%, of which 17 of the 22 re-hospitalisations were heart failure related. Conclusion: Dilated cardiomyopathy in Africans primarily affects young males. In our cohort, this disease was associated with an all-cause mortality of 19% in one year. In SSA, large multicenter studies are required to investigate this disease’s pathogenesis and outcomes.Item Switching from Sucrose-Formulated rFVIII to Octocog Alfa (BAY 81-8973) Prophylaxis Improves Bleed Outcomes in the LEOPOLD Clinical Trials(Dove Medical Press Limited, 2023-06) Mahlangu, Johnny; Kenet, Gili; Moulton, Thomas; Wicklund, Brian M.; Ahuja, Sanjay P.; Escobar, MiguelIntroduction: Previous clinical trials established the efficacy and safety of sucrose-formulated recombinant factor (F) VIII (rFVIIIFS/Kogenate FS®/Helixate FS®) and octocog alfa (BAY 81–8973/Kovaltry®; LEOPOLD trials). Aim: To report the results of a post hoc subgroup analysis assessing efficacy and safety outcomes in patients with hemophilia A who were receiving rFVIII-FS prior to enrolling into the LEOPOLD I Part B and LEOPOLD Kids Part A clinical trials and switching to octocog alfa. Methods: LEOPOLD I Part B (NCT01029340) and LEOPOLD Kids Part A (NCT01311648) were octocog alfa Phase 3, multinational, open-label studies in patients with severe hemophilia A aged 12–65 years and ≤12 years, respectively. Annualized bleeding rate (ABR) was the efficacy endpoint for both studies. Safety endpoints included adverse events (AEs) and development of FVIII inhibitors. Results: Of the 113 patients in both LEOPOLD trials, 40 (35.4%) patients received rFVIII-FS prophylaxis pre-study and had data available for pre-study total ABR. In LEOPOLD I Part B (n = 22, 35.5%), median (Q1; Q3) total ABR decreased from 2.5 (0.0; 9.0) pre-study to 1.0 (0.0; 6.8), and from 1.0 (0.0; 6.0) pre-study to 0.0 (0.0; 6.02) in LEOPOLD Kids Part A (n = 18, 35.3%). Octocog alfa was well tolerated, and no patients had drug-related serious AEs or inhibitors. Conclusion: Treatment with octocog alfa prophylaxis appeared to have a favorable risk–benefit profile compared with rFVIII-FS and thus could be an effective and improved alternative strategy for individualized treatment for children, adolescent and adult patients with severe hemophilia A currently on rFVIII-FS treatmentItem Dopamine Transporter Deficiency Syndrome (DTDS): expanding the clinical phenotype and precision medicine approaches(MDPI, 2023-06) Waddington, Simon N.; Ng, Joanne; Barral, Serena; Kurian, Manju A.Infantile parkinsonism-dystonia due to dopamine transporter deficiency syndrome (DTDS) is an ultrarare childhood movement disorder caused by biallelic loss-of-function mutations in the SLC6A3 gene. Advances in genomic analysis have revealed an evolving spectrum of SLC6A3-related neurological and neuropsychiatric disorders. Since the initial clinical and genetic characterisation of DTDS in 2009, there have been thirty-one published cases with a variety of protein-truncating variants (nonsense variants, splice-site changes, and deletions) and missense changes. Amino acid substitutions result in mutant proteins with impaired dopamine transporter function due to reduced transporter activity, impaired dopamine binding, reduced cell-surface expression, and aberrant posttranslational protein modification with impaired glycosylation. In this review, we provide an overview of the expanding clinical phenotype of DTDS and the precision therapies in development, including pharmacochaperones and gene therapy.Item Advancing HIV Drug Resistance Technologies and Strategies: insights from South Africa’s Experience and Future Directions for Resource-Limited Settings(MDPI, 2023-06) Steegen, Kim; Hans, Lucia; van Zyl, Gert U.; Claassen, Mathilda; Khan, Aabida; Pillay, Melendhran; Govender, Subitha; Bester, Phillip A.; van Straaten, Johanna M.; Kana, Vibha; Cutler, Ewaldé; Kalimashe, Monalisa N.; Lebelo, Ramokone L.; Moloi, Mokopi B. H.Monitoring of HIV drug resistance (HIVDR) remains critical for ensuring countries attain and sustain the global goals for ending HIV as a public health threat by 2030. On an individual patient level, drug resistance results assist in ensuring unnecessary treatment switches are avoided and subsequent regimens are tailored on a case-by-case basis, should resistance be detected. Although there is a disparity in access to HIVDR testing in high-income countries compared to low- and middle-income countries (LMICS), more LMICs have now included HIVDR testing for individual patient management in some groups of patients. In this review, we describe different strategies for surveillance as well as where HIVDR testing can be implemented for individual patient management. In addition, we briefly review available technologies for HIVDR testing in LMICs, including Sanger sequencing, next-generation sequencing, and some point-of-care options. Finally, we describe how South Africa has implemented HIVDR testing in the public sector.Item Laboratory services in the context of prevention of mother‑to‑child transmission of HIV testing requirements in Copperbelt Province, Zambia: a qualitative inquiry(BioMed Central, 2023-07) Mwanza, Jonathan; Doherty, Tanya; Lubeya, Mwansa Ketty; Gray, Glenda E.; Mutale, Wilbroad; Kawonga, MaryIntroduction: Reliable and timely laboratory results are crucial for monitoring the Prevention of the Mother-to-Child Transmission (PMTCT) cascade, particularly to enable early HIV diagnosis and early intervention. We sought to explore whether and how laboratory services have been prepared to absorb new testing requirements following PMTCT Testand-Treat policy changes in three districts of Zambia. Method: We employed in-depth interviews and thematic data analysis, informed by the health system dynamic framework. Twenty-Six health workers were purposively selected and a document review of laboratory services in the context of PMTCT was undertaken. All face-to-face interviews were conducted in three local government areas in the Copperbelt Province (one urban and two rural) between February 2019 and July 2020. We extracted notes and markings from the transcripts for coding. Different codes were sorted into potential themes and the data extracted were put within the identified themes. Trustworthiness was confirmed by keeping records of all data field notes, transcripts, and reflexive journals. Results: The findings revealed that the health system inputs (infrastructure and supplies, human resources, knowledge, and information and finance) and service delivery were unequal between the rural and urban sites, and this affected the ability of health facilities to apply the new testing requirements, especially, in the rural-based health facilities. The major barriers identified include gaps in the capacity of the existing laboratory system to perform crucial PMTCT clinical and surveillance functions in a coordinated manner and insufficient skilled human resources to absorb the increased testing demands. The centralized laboratory system for HIV testing of mothers and exposed neonates meant facilities had to send specimens to other facilities and districts which resulted in high turnaround time and hence delayed HIV diagnosis. Conclusion: New guidelines implemented without sufficient capacitation of health system laboratory capacity severely limited the effectiveness of PMTCT program implementation. This study documented the areas relating to health system inputs and laboratory service delivery where greater support to enable the absorption of the new testing requirements is needed.Item The impact of diferences in plasma glucose between glucose oxidase and hexokinase methods on estimated gestational diabetes mellitus prevalence(Nature Research, 2019-05) Dickson, Lynnsay M.; Buchmann, Eckhart J.; Janse Van Rensburg, Charl; Norris, Shane A.We evaluated the extent of measurement discordance between glucose oxidase and hexokinase laboratory methods and the efect of this on estimated gestational diabetes mellitus (GDM) prevalence in a routine clinical setting. 592 consecutive urban African women were screened for GDM. Paired venous specimens were submitted to two independent calibrated laboratories that used either method to measure plasma glucose concentrations. World Health Organisation diagnostic criteria were applied. GDM prevalence determined by the glucose oxidase and hexokinase methods was 6.9% and 5.1% respectively. The overall GDM prevalence was 9%. Only 34% of GDM positive diagnoses were common to both laboratory methods. Bland Altman plots identifed a bias of 0.2mmol/l between laboratory methods. Plasma glucose concentrations measured by the glucose oxidase method were more platykurtic in distribution. Low diagnostic agreement between laboratory methods was further indicated by a Cohen’s kappa of 0.48 (p<0.001). Reports of GDM prevalence using either the glucose oxidase or hexokinase laboratory methods may not be truly interchangeable or directly comparable.Item The burden of cancers associated with HIV in the South African public health sector, 2004–2014: a record linkage study(2019-05) Dhokotera, Tafadzwa; Bohlius, Julia; Spoerr, Adrian; Egger, Matthias; Ncayiyana, Jabulani; Olago, Victor; Singh, Elvira; Sengayi, MazvitaIntroduction: The impact of South Africa’s high human immunodeficiency virus (HIV) burden on cancer risk is not fully understood, particularly in the context of antiretroviral treatment (ART) availability. We examined national cancer trends and excess cancer risk in people living with HIV (PLHIV) compared to those who are HIV-negative. Methods: We used probabilistic record linkage to match cancer records provided by the National Cancer Registry to HIV data provided by the National Health Laboratory Service (NHLS). We also used text search of specific HIV terms from the clinical section of pathology reports to determine HIV status of cancer patients. We used logistic and Joinpoint regression models to evaluate the risk and trends in cancers in PLHIV compared to HIV-negative patients from 2004 to 2014. In sensitivity analysis, we used inverse probability weighting (IPW) to correct for possible selection bias. Results: A total of 329,208 cancer cases from public sector laboratories were reported to the NCR from 2004 to 2014 with the HIV status known for 95,279 (28.9%) cancer cases. About 50% of all the female cancer cases (n = 30,486) with a known status were HIV-positive. PLHIV were at higher risk of AIDS-defining cancers (Kaposi sarcoma [adjusted OR:134, 95% CI:111–162], non-Hodgkin lymphoma [adjusted OR:2.73, 95% CI:2.56–2.91] and, cervix [adjusted OR:1.70, 95% CI:1.63–1.77], conjunctival cancer [adjusted OR:21.5, 95% CI:16.3–28.4] and human papilloma virus (HPV) related cancers (including; penis [adjusted OR:2.35, 95% CI:1.85–2.99], and vulva [adjusted OR:1.94, 95% CI:1.67–2.25]) compared to HIV-negative patients. Analysis using the IPW population yielded comparable results. Conclusion: There is need for improved awareness and screening of conjunctival cancer and HPV-associated cancers at HIV care centres. Further research and discussion is warranted on inclusive HPV vaccination in PLHIV.Item The prevalence of malnutrition and growth percentiles for urban South African children(BMC Public Health, 2019-05) Nyati, Lukhanyo H.; Pettifor, John M.; Norris, Shane A.Background: Low- and middle-income countries (LMIC) are experiencing a double-burden of malnutrition characterised by high prevalence of both under- and over-nutrition. We set out using data from the mixedlongitudinal Birth-to-Twenty Plus (Bt20+) birth cohort, to evaluate the patterns of malnutrition and growth in a large South African (SA) city by; (i) assessing the prevalence of undernutrition from birth to 5 years of age and overweight and obesity from ages 2 to 21 years in black and white, male and female children, and (ii) determining percentiles for height, weight, BMI, waist and hip circumferences and comparing the centiles to American and Dutch references. Methods: Height, weight, waist and hip circumferences were measured on urban black and white SA children from the Bt20+. A total of 3273 children born between April and June 1990 in the Greater Johannesburg Metropolitan area were included in the cohort. Z-scores were derived using the WHO 2006 child growth standards (0–5 years), for defining stunting, underweight and wasting. The International Obesity Task Force (IOTF) references were used to define overweight and obesity. Percentiles were developed using the lambda mu sigma (LMS) method and compared to American and Dutch references. Results: Black children were consistently shorter and black males lighter than white children and American references. The prevalence of stunting peaked at 2 years and was significantly higher in males than females and in black than white children. Black females had a greater prevalence of overweight and obesity than black males from 10 to 17 years. The percentiles for black females for weight and BMI were similar to those of South African white and American references but both black and white South African females had lower waist circumferences than American references. Conclusion: The growth percentiles show that young South African urban black females are experiencing general but not central obesity due to a secular change which is faster in weight than height. High levels of undernutrition persist alongside high levels of over-nutrition with adolescence being a critical period for the upsurge in obesity in females. Early intervention is needed to combat the rise in obesity.Item Religiosity and sexual abstinence among Nigerian youths: does parent religion matter?(BioMed Central, 2019-04) Somefun, Oluwaseyi DolapoBackground: Religion plays an important role in youth behaviours, making it a significant factor in the discourse on youth sexuality in sub-Saharan Africa. Several studies have found that religion and religiosity play an important role in the sexual behaviours of young people. However, little research in Nigeria has examined the mechanisms through which religiosity influences youth sexual behaviour and if parents’ religion moderates this relationship. Guided by the social control theory, this paper contributes to the existing literature by examining the relationship between religiosity and youth sexual behaviour. Methods: Data for the study came from 2399 male and female youth aged 16–24 years in four states purposively selected from four regions in Nigeria. Abstinence was the sexual behaviour of interest. Logistic regression was used to examine this relationship. Results: Results showed that 68% of the youth had never had sex. Religiosity was a protective factor for youth sexual behaviour and this positive association was still evident even after controlling for other covariates. Youth who were highly religious (OR – 1.81, CI- 1.13-2.88) had significantly higher odds of abstaining compared to their counterparts who were not religious. Conclusion: Religiosity is a protective factor for sexual abstinence among youth in Nigeria. Policy makers can work around using religious institutions for behavioural change among youth in Nigeria.Item Prevention care for secondary health conditions among people living with spinal cord injuries: research protocol(Springer Nature, 2019-03) Pilusa, S.; Myezwa, Hellen; Potterton, JoanneObjective: People living with spinal cord injuries are at a high risk to experience preventable secondary health conditions in their lifetime, which can lead to rehospitalisation and death. Given the fact that spinal cord injury is a long term disability requiring on-going care, there is need to strengthen prevention of secondary health conditions. This study aims to establish factors influencing prevention care for secondary health conditions among people living with spinal cord injuries in a metropolitan area in order to develop a prevention model of care. Results: A record review of patients living with spinal cord injuries will be conducted to identify the prevalence of secondary health conditions and associated factors. Semi-structured interviews will be conducted on patients living with spinal cord injuries, their caregivers and therapists to explore the contextual factors (personal and environmental factors) influencing the prevention of secondary health conditions. Thematic analysis will be used to identify the themes. Nominal group technique will be used to develop the prevention model of care for secondary health conditions. This study will be conducted at a tertiary and specialised rehabilitation hospital in South Africa.