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Item Computer-based cognitive training for cognitive development of alcohol-exposed children in South Africa: a feasibility randomised control trial(Sage Publications, 2023) Louw, Jacobus; van Heerden, Alastair; Broodryk, Mandi; White, Liska; Olivier, Leana; Tomlinson, MarkChildren exposed to alcohol in utero may suffer from cognitive and physical sequelae. The most impactful damage in terms of daily functioning is to higher order cognitive functions involved in planning and goal-directed behaviour, referred to as executive functions. Cognitive training interventions are used as a remedial tool for executive function deficits but require implementation by professionals. For the South African context, where resources are limited, a tablet computer-based cognitive training game was developed. This study aimed to establish the feasibility of implementing and evaluating this intervention in South Africa for children exposed to alcohol prenatally. This was a three-arm feasibility randomised control trial comparing an alcohol exposed intervention arm, to an alcohol exposed control arm, and a non-exposed normative arm. Arm allocation was based on self-reported maternal alcohol use during a structured interview. To assess feasibility, we evaluated participant recruitment and barriers to implementation. Executive functions were measured at baseline and following intervention to evaluate the preliminary impact of the intervention. No significant differences were found between the three arms on the post-intervention assessments. The retention rate was acceptable for a randomised control trial; however, there was significant variance in the length of time spent playing the game overall. The majority of participants learned to play the game quickly and progressed through the difficulty levels. In conclusion, a full randomised control trial using the recruitment, randomisation and implementation method would be suitable in the South African context. The statistical outcomes of this trial do not support a full-scale randomised control trial of this intervention.Item Morphometry of the patellar tendon using a simple tracing method: a gold standard for anterior cruciate ligament reconstruction(Korean Association of Anatomists, 2023-06) Latiff, Sabiha; Olateju, Oladiran IbukunoluThe anterior cruciate ligament (ACL) is mostly damaged in sporting activities. To reconstruct the damaged ACL, a patellar tendon (PT) is often the most preferred graft due to its fast healing and bone integration i.e. bone-patellar tendon-bone graft. Suitability of the PT often depends on the morphometric profile of the tendon. This study reported on the harvestable surface area (SA) of the tendon using a simple tracing method. The PT of 79 adult formalin–fixed cadavers of South Africans of European Ancestry were dissected, and the margins of the PT were traced on a wax paper before the tracings were scanned. The SA, straight proximal width (SPW), curved proximal width (CPW), straight distal width (SDW), curved distal width (CDW) and length of tendon (LOT) from the digitized image of the PT was measured. In addition, the length of the lower limbs was measured to normalize the measurements. The results showed no significant side differences, and the measurements were not sexually dimorphic. A strong correlation was reported for SA vs. LOT, SPW vs. CPW and SDW vs. CDW for both sexes and sides. The presented morphological profile provides additional information on the usability of the graft and with respect to healing and recovery.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 Current evidence on improving influenza vaccine uptake in low- and middle-income countries: a scoping review of determinants and interventions(Elsevier, 2025-03) Tsotetsi, Lerato; Msibi, Tshepiso; Mashamba, Mulalo; Dietrich, Janan; Alam, PrimaInfluenza is a vaccine-preventable disease affecting three to five million individuals across the globe annually. Low- and middle-income countries (LMICs) bear substantial health and economic consequences of influenza- related mortality. Despite this disproportionate burden, influenza vaccinations are seldom used across LMICs. In this article, we reviewed current evidence on improving influenza vaccine uptake within LMICs by examining key determinants and interventions. We conducted a scoping review of peer-reviewed studies pertaining to influenza vaccine uptake in LMICs. We searched five electronic databases for articles published 2014–2024, using terms relating to influenza vaccines, interventions, and context. Twenty-four articles met the inclusion criteria with sample sizes ranging from 38 to 9420. The authors followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines and synthesized the included articles using thematic analysis. All studies included in this review were cross-sectional and primarily used quantitative surveys. Most of the included studies were conducted in Sub-Saharan Africa (South Africa, Kenya, Malawi, and Sierra Leone) and the Middle East and North Africa (Tunisia, Jordan, Lebanon, and Egypt). Articles predominantly targeted vulnerable populations including elderly, pregnant women, and young children as well as healthcare workers. Participants across the included studies reported high levels of willingness to receive the influenza vaccination but lower levels of uptake. Having positive perceptions and attitudes towards the efficacy and safety of the vaccine, greater belief in disease susceptibility, physician recommendations, and a history of being vaccinated were associated with greater willingness to receive the influenza vaccine. Six articles explored national campaigns or researcher- led interventions to improve influenza vaccine uptake with educational campaigns positively changing attitudes towards influenza vaccination and integration of year-round vaccination campaigns with routine services as an effective vaccine delivery method.Item Trends in national and ethnic burden of ovarian cancer mortality in South Africa (1999–2018): a population based, age-period-cohort and join point regression analyses(BioMed Central, 2025-03) Olorunfemi, Gbenga; Libhaber, Elena; Musenge, Eustasius; Ezechi, Oliver C.Ovarian cancer is the most lethal and third leading cause of gynaecological cancers globally and in South Africa (SA). However, its current mortality trends have not been evaluated in most sub-Saharan African Countries including South Africa that is currently undergoing epidemiological and health transitions. We evaluate the trends in the ovarian cancer mortality rates in SA over 20 years (1999–2018). Methods: Crude (CMR) and age standardised mortality rates (ASMR) of ovarian cancer was calculated based on national mortality data of South Africa. The overall and ethnic trends of ovarian cancer mortality among women aged 15 years and older from 1999 to 2018 was assessed using the Join point regression model, while Age-period-cohort regression analysis was conducted to evaluate the underlying impact of age, period and cohort on ovarian cancer mortality. Results: In all, 12,721 ovarian cancer deaths were reported in South Africa from 1999 to 2018 and the mortality rates increased from 2.34 to 3.21 per 100,00 women at 1.8% per annum. In 2018, the overall mean age at ovarian cancer death in South Africa was 62.30±14.96 years while the mean age at death among Black women (58.07±15.56 years), was about 11 years earlier than among White women (69.48±11.71 years). In 2018, the White ethnic group (4.93 deaths per 100,000 women) had about doubled the ovarian cancer ASMR for the non-Whites (Indian/Asians, 2.92/100,000 women, mixed race, 2.49/100,000 women and Black women (2.36/ 100,000 women). All the ethnic groups had increased ASMR with Black women (Average annual percent change, [AAPC]: 4.7%, P-value<0.001) and Indian/Asian women (AAPC: 2.5%, P-value<0.001) having the highest rise. Cohort mortality risk ratio of ovarian cancer increased with successive birth cohort from 0.35 among 1924–1928 birth cohorts to 3.04 among 1999–2003 cohort and the period mortality risk increased by about 13% and 7.5% from 1999 to 2003 to 2004–2008 (RR: 0.87, 95% CI: 0.80–0.94), and from 2004 to 2008 to 2009–2013 (RR: 1.075, 95% CI:1.004–1.152) respectively. The longitudinal age analysis revealed that ovarian cancer increased with age, but there was an exponential increase from 55 years. Conclusions: Our study showed that there was increasing trends in ovarian cancer mortality among all the South African ethnic groups, driven partly by increasing cohort and period mortality risks. We therefore highlight the huge burden of ovarian cancer in SA and the need for targeted intervention. Public health interventions geared towards reducing ovarian cancer mortality should be instituted and ethnic disparity should be incorporated in the cancer control policyItem ‘We do not like talking about our problems’: socialization and idealized masculinity as drivers of help-seeking avoidance among college men in South Africa(BioMed Central, 2025-03) Sikweyiya, Yandisa; Jewkes, Rachel; Machisa, Mercilene; Mahlangu, Pinky; Brooke-Sumner, Carrie; Gibbs, Andrew; Dartnall, Elizabeth; Pillay, ManagaBackground: This article explores how identities and contexts influence help-seeking avoidance behaviour among college men. Methods: This exploratory qualitative study purposively selected 88 male students (aged 18–30) from some universities and Technical and Vocational Training colleges (TVETs) in South Africa. Data were collected through focus group discussions (FGDs). Eight FGDs were conducted, one in each selected university (n = 2) and TVETs (n = 6) in 2018–2019. Data were analyzed using a thematic analysis approach. Results: We found that college men’s early life experiences and socialisation strongly influenced their ability to express emotion and access services when in need of help. The data also revealed a masculinity that men aspired to and wanted to be seen as embracing or personifying while on campus. Most men ascribed to an ideal of masculinity that made it difficult for them to share their feelings (e.g., emotional pain, sadness; and bottle their emotions) and seek help from campus-based counselors or peers. The few men who reported using campus mental health support services appraised them as unsuitable and unhelpful for them, and indicated a preference for services that were more culturally relevant. Most men indicated a preference for male counselors, of which there were very few. Conclusions: These findings may be useful for the formulation of evidence-based context-specific and culturally sensitive approaches for increasing men’s access to mental health and psychological support services on South African college campuses.