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Item A long walk to freedom: the epidemiology of penetrating trauma in South Africa- analysis of 4 697 patients over a six year period at Chris Hani Baragwanath Academic HospitalBhana, Malini; Fru, Pascaline; Plani, FrancoBackground: Despite the city of Johannesburg having one of the highest rates of crime in the world, no national databank for trauma exists. This study profiles the victims of penetrating trauma and identifies geographical areas in which it occurs, while describing the outcomes and patterns of injury. Methods: A retrospective study including penetrating trauma patients triaged as Priority 1, presenting at the Chris Hani Baragwanath Academic Hospital's (CHBAH) trauma department over a six-year period (2011-2016). Results: A total of 4 697 patients were included. The majority of victims were Black African males (92.1%) between the ages of 29-40 years, and stabbings were the most common mechanism of injury (71.8%), followed by gunshots. The commonest body area affected was the thorax, with a consequent haemothorax the most likely result. Weekends accounted for over 48% of all presentations - the last weekend of the month being the busiest. Region D was the area in Johannesburg with the highest trauma incidence (51.9%), with the oldest townships in Soweto found to be "hot spots". Conclusion: Penetrating trauma is inherently linked to alcohol abuse and interpersonal violence in South Africa,1 primarily affecting its young economic, working-class citizens. The data provided some insight into the burden, structure and challenges of our trauma system. These should be regarded as opportunities to implement change and improve our surveillance and prevention, beginning with a national trauma databankItem A qualitative analysis of community health worker perspectives on the implementation of the preconception and pregnancy phases of the Bukhali randomised controlled trial(Public Library of Science, 2024) Norris, Shane A.; Soepnel, Larske M.; Mabetha, Khuthala; Motlhatlhedi, Molebogeng; Nkosi, Nokuthula; Lye, Stephen; Draper, Catherine E.Community health workers (CHWs) play an important role in health systems in low- and middle- income countries, including South Africa. Bukhali is a CHW-delivered intervention as part of a randomised controlled trial, to improve the health trajectories of young women in Soweto, South Africa. This study aimed to qualitatively explore factors influencing implementation of the preconception and pregnancy phases of Bukhali, from the perspective of the CHWs (Health Helpers, HHs) delivering the intervention. As part of the Bukhali trial process evaluation, three focus group discussions were conducted with the 13 HHs employed by the trial. A thematic approach was used to analyse the data, drawing on elements of a reflexive thematic and codebook approach. The following six themes were developed, representing factors impacting implementation of the HH roles: interaction with the existing public healthcare sector; participant perceptions of health; health literacy and language barriers; participants’ socioeconomic constraints; family, partner, and community views of trial components; and the HH-participant relationship. HHs reported uses of several trial-based tools to overcome implementation challenges, increasing their ability to implement their roles as planned. The relationship of trust between the HH and participants seemed to function as one important mechanism for impact. The findings supported a number of adaptations to the implementation of Bukhali, such as intensified trial-based follow-up of referrals that do not receive management at clinics, continued HH training and community engagement parallel to trial implementation, with an increased emphasis on health-related stigma and education. HH perspectives on intervention implementation highlighted adaptations across three broad strategic areas: navigating and bridging healthcare systems, adaptability to individual participant needs, and navigating stigma around disease. These findings provide recommendations for the next phases of Bukhali, for other CHW-delivered preconception and pregnancy trials, and for the strengthening of CHW roles in clinical settings with similar implementation challenges.Item A qualitative exploration of the reasons and infuencing factors for pregnancy termination among young women in Soweto, South Africa: a Socio-ecological perspective(BioMed Central (BMC), 2024) Norris, Shane A.; Mabetha, Khuthala; Soepnel, Larske M.; Sewanyana, Derrick; Draper, Catherine E.; Lye, StephenBackground: Pregnancy termination is an essential component of reproductive healthcare. In Southern Africa, an estimated 23% of all pregnancies end in termination of pregnancy, against a backdrop of high rates of unintended pregnancies and unsafe pregnancy terminations, which contributes to maternal morbidity and mortality. Understanding the reasons for pregnancy termination may remain incomplete if seen in isolation of interpersonal (including family, peer, and partner), community, institutional, and public policy factors. This study therefore aimed to use a socio-ecological framework to qualitatively explore, in Soweto, South Africa, i) reasons for pregnancy termination amongst women aged 18-28 years, and ii) factors characterising the decision to terminate. Methods: In-depth interviews were conducted between February to March 2022 with ten participants of varying parity, who underwent a termination of pregnancy since being enrolled in the Bukhali trial, set in Soweto, South Africa. A semi-structured, in-depth interview guide, based on the socioecological domains, was used. The data was analysed using reflexive thematic analysis, and a deductive approach. Results: An application of the socio-ecological framework indicated that the direct reasons to terminate a pregnancy fell into the individual and interpersonal domains of the socioecological framework. Key reasons included financial dependence and insecurity, feeling unready to have a child (again), and a lack of support from family and partners for the participant and their pregnancy. In addition to these reasons, Factors that characterised the participants' decision experience were identified across all socio-ecological domains and included the availability of social support and (lack of) accessibility to termination services. The COVID-19 pandemic and resultant lockdown policies also indirectly impacted participants' decisions through detrimental changes in interpersonal support and financial situation. Conclusions: Amongst the South African women included in this study, the decision to terminate a pregnancy was made within a complex structural and social context. Insight into the reasons why women choose to terminate helps to better align legal termination services with women's needs across multiple sectors, for example by reducing judgement within healthcare settings and improving access to social and mental health support.Item An all-oral 6-month regimen for multidrug resistant Tuberculosis: A multicenter randomized controlled clinical trial (the Next Study)Esmail, Aliasgar ; Oelofse, Suzette ; Lombard, Carl ; Perumal, Rubeshan ; Variava, Ebrahim ; Martinson, NeilRationale: Improving treatment outcomes while reducing drug toxicity and shortening the treatment duration to 6 months remains an aspirational goal for the treatment of multi drug resistant /rifampicin-resistant tuberculosis(MDR/RR-TB). Objectives: To conduct a multicenter randomized controlled trial in adults with MDR/RR-TB(i.e., without resistance to fluoroquinolones or aminoglycosides) . Methods: Participants were randomly assigned(1:1ratio)to a 6 month all-oral regimen that included levofloxacin, bed aquiline, and linezolid or the standard-of-care(SOC)>9-month World Health Organization(WHO)-approved injectable-based regimen. The primary endpoint was a favorable WHO-defined treatment outcome (which mandates that prespecified drugs substitution is counted as an unfavorable outcome)24 months after treatment initiation. The trial was stopped prematurely when bed aquiline-based therapy became the standard of care in South Africa. Measurements and Main Results: In total,93 of 111 randomized participants(44 in the comparator arm and 49 in the intervention alarm) were included in the modified intention-to-treatanalysis;51(55%)were HIV coinfected(medianCD4count,158cells/ml).Participants in the intervention arm were 2.2 times more likely to experience a favorable 24-month outcome than participants in the SOC arm(51%[25of49]vs. 22.7%[10of44];riskratio,2.2[1.2–4.1];P=0.006).Toxicity-related drug substitution occurred more frequently in the SOC arm(65.9%[29of44] vs.34.7%[17of49];P=0.001)],82.8%(24of29)owing to kanamycin (mainly hearing loss; replaced by bed aquiline) in the SOC arm, and 64.7% (11of17) owing to fluoroquinolones or aminoglycosides (mainly anemia) in the intervention alarm. Adverse event–related treatment discontinuation in the safety population was more common in the SOC arm(56.4%[31of55]vs.32.1%[17of 56];P=0.007).However, grade 3 adverse events were more common in the intervention alarm(55.4%[31of56]vs.32.7[18of55];P=0.022). Culture conversion was significantly better in the intervention arm (hazardratio,2.6[1.4–4.9];P=0.003)after censoring those with bed aquiline replacement in the SOC arm(and this pattern remained consistent after censoring for drug replacement in both arms ;P=0.01). Conclusions: Compared with traditional injectable-containing regimens, an all-oral 6-month levofloxacin, bed aquiline, and linezolid–containing MDR/RR-TB regimen was associated with a significantly improved 24-month WHO-defined treatment outcome (predominantly owing to toxicity-related drugs substitution).However, drug toxicity occurred frequently in both arms. These findings form strategies to develop future regimens for MDR/RR-TB. Clinical trial registered with www.clinicaltrials.gov (NCT02454205).Item Analysis of surgical mortalities using the fishbone model for quality improvement in surgical disciplinesMoeng, Maeyane S.; Luvhengo, Thifhelimbilu E.Background: The healthcare industry is complex and prone to the occurrence of preventable patient safety incidents. Most serious patient safety events in surgery are preventable. Aim: This study was conducted to determine the rate of occurrence of preventable mortalities and to use the fishbone model to establish the main contributing factors. Methods: We reviewed the records of patients who died following admission to the surgical wards. Data regarding their demography, diagnosis, acuity, comorbidities, categorization of death and contributing factors were extracted from the Research Electronic Data Capture (REDCap) database. Factors which contributed to preventable and potentially preventable mortalities were collated. The fishbone model was used for root cause analysis. The study received prior ethical clearance (M190122). Results: Records of 859 mortalities were found, of which 65.7% (564/859) were males. The median age of the patients who died was 49 years (IQR: 33–64 years). The median length of hospital stay before death was three days (IQR: 1–11 days). Twenty-four percent (24.1%) of the deaths were from gastrointestinal (GIT) emergencies, 18.4% followed head injury and 17.0% from GIT cancers. Overall, 5.4% of the mortalities were preventable, and 41.1% were considered potentially preventable. The error of judgment and training issues accounted for 46% of mortalities. Conclusion: Most surgical mortalities involve males, and around 46% are either potentially preventable or preventable. The majority of the mortality were associated with GIT emergencies, head injury and advanced malignancies of the GIT. The leading contributing factors to preventable and potentially preventable mortalities were the error of judgment, inadequate training and shortage of resources.Item Cash transfer interventions for sexual health: meanings and experiences of adolescent males and females in inner-city Johannesburg(BMC, 2018) Khoza, Nomhle; Stadler, Jonathan; MacPhail, Catherine; Chikandiwa, Admire; Brahmbhatt, Heena; Delany-Moretlwe, SineadBackground: In sub-Saharan Africa, there is growing interest in the use of cash transfer (CT) programs for HIV treatment and prevention. However, there is limited evidence of the consequences related to CT provision to adolescents in low-resourced urban settings. We explored the experiences of adolescents receiving CTs to assess the acceptability and unintended consequences of CT strategies in urban Johannesburg, South Africa. Methods: We collected qualitative data during a pilot randomized controlled trial of three CT strategies (monthly payments unconditional vs. conditional on school attendance vs. a once-off payment conditional on a clinic visit) involving 120 adolescents aged 16–18 years old in the inner city of Johannesburg. Interviews were conducted in isiZulu, Sesotho or English with a sub-sample of 49 participants who adhered to study conditions, 6 months after receiving CT (280 ZAR/ 20 USD) and up to 12 months after the program had ended. Interviews were transcribed and translated by three fieldworkers. Codes were generated using an inductive approach; transcripts were initially coded based on emerging issues and subsequently coded deductively using Atlas.ti 7.4. Results: CTs promoted a sense of independence and an adult social identity amongst recipients. CTs were used to purchase personal and household items; however, there were gender differences in spending and saving behaviours. Male participants’ spending reflected their preoccupation with maintaining a public social status through which they asserted an image of the responsible adult. In contrast, female participants’ expenditure reflected assumption of domestic responsibilities and independence from older men, with the latter highlighting CTs’ potential to reduce transactional sexual partnerships. Cash benefits were short-lived, as adolescents reverted to previous behavior after the program’s cessation. Conclusion: CT programs offer adolescent males and females in low-income urban settings a sense of agency, which is vital for their transition to adulthood. However, gender differences in the expenditure of CTs and the effects of ending CT programs must be noted, as these may present potential unintended risks.Item Cognitive and motor development in 3 to 6 year old children born to mothers with Hyperglycaemia first detected in pregnancy in an urban African populationSoepnel, Larske ; Nicolaou, Veronique ; Draper, Catherine ; Levitt, N. ; Klipstein-Grobusch, Kerstin ; Norris, ShaneObjectives: Hyperglycaemia first detected in pregnancy (HFDP), on the rise in urban sub-Saharan Africa (SSA), may negatively impact foetal neurodevelopment, with potential long-term cognitive consequences for the child. Data on this association from SSA is lacking, and we aimed to investigate the association in 3- to 6-year-old children in Soweto, South Africa. Methods: In this comparative study, we compared cognitive skills measured with the Herbst Early Childhood Development Criteria test in 95 children born to mothers with HFDP and 99 participants unexposed to maternal HFDP. Fine and gross motor skills were secondary outcomes. Ordinal regression analysis with known confounders was performed for children born at-term. Results Of children exposed to HFDP born at-term, 24.3% scored ‘high’ and 25.7% scored ‘low’ in the cognitive subsection of the test, as opposed to 37.7% and 12.9% in the HFDP-unexposed group, respectively. In ordinal regression, exposed participants had a significantly lower odds of scoring in a higher cognitive category when adjusting for maternal confounders and socio-economic status (OR 0.33, 95% CI 0.15–0.74, p = 0.007). No difference was found in gross motor development between the two groups; differences in fine motor development were attenuated after adjustment for maternal pregnancy factors and household socioeconomic status (OR 0.62, 95% CI 0.28–1.37, p = 0.239). Conclusions: for Practice Exposure to HFDP was negatively associated with cognitive development at preschool age. Optimising maternal (preconception) health and early childhood cognitive stimulation could help more children reach their developmental potential.Item Comorbidities in black South Africans with established rheumatoid arthritisLala, Vikash ; Mohammed, Tickly; Musenge, Eustasius ; Govind, NimmishaObjective: Comorbidities contribute both to morbidity and mortality in rheumatoid arthritis (RA). The aim of the current study was to investigate the prevalence and spectrum of comorbidities in South Africans with established RA. Methods: A retrospective, consecutive case record review of 500 Black South African patients with established disease of ≥5 years attending a tertiary rheumatology service was performed. Common comorbidities including those listed in the Charlson Comorbidity Score (CCS) were documented. Results: Most patients, 463 known alive (AG) and 37 known deceased (DG), were female (87%). Mean (SD) age and disease duration were 60 (11.1) and 10.7 (5.0) years respectively, and 98% had ≥1 comorbidities. Median CCS was 2, significantly higher in DG than AG (4 vs 2, P < .0001). Despite hypertension (70%) and hypercholesterolemia (47%) being the commonest comorbidities overall and type 2 diabetes (T2D) occurring in 15.4%, clinical cardiovascular events were rare (0.6%). Peptic ulcer disease (odds ratio [OR] = 8.67), congestive cardiac failure (OR = 7.09), serious infections (OR = 7.02) and tuberculosis (OR = 2.56) were significantly more common in DG than AG. Multivariate analysis showed that American College of Rheumatology functional class 3/4 was associated with increased risk for serious infections (OR = 3.84) and tuberculosis (OR = 2.10). Conclusion: Despite the high burden of cardiometabolic comorbidities in South Africans with established RA, cardiovascular events were rare. Serious infections and tuberculosis, both associated with severe functional disability, are a major cause of morbidity and mortality.Item Comparing a range of potassium-enriched low sodium salt substitutes to common salt: results of taste and visual tests in South African adults(Elsevier, 2024) Norris, Shane A.; Crouch, Simone H.; Ware, Lisa J.; Schutte, Aletta E.Background and aims: Potassium-enriched low sodium salt substitutes (LSSS), which replace a proportion of sodium chloride (NaCl) with potassium chloride (KCl), have been shown to reduce blood pressure and offer a potential solution to address the high burden of hypertension in South Africa. However, it is unknown which proportions of KCl in LSSS are acceptable. We compared the taste and visual acceptability of various LSSS in South African adults. Methods and results: Fifty-six adults underwent double-blind taste and visual tests of four LSSS (35%KCl/65%NaCl; 50%KCl/50%NaCl; 66%KCl/34%NaCl; 100%KCl) in comparison to 100%NaCl (common salt). Participants scored each product by taste ranking, taste perception and likeliness to use. Participants then visually inspected the five products and attempted to identify which was which. Almost half (45 %) of participants ranked the taste of 50%KCl/50 %NaCl as fantastic or really good. Furthermore, 62 % of participants liked and would be happy to use the 50 %KCl/50 %NaCl or felt this tasted like common salt. Only 12 % rated the 100%KCl highly for taste, and over half reported being unlikely to use this. Most participants (57.3 % and 36.4 %) were able to visually identify 100%NaCl and 100%KCl, while identification of other blends was generally poor. Responses were similar for 35%KCl/65%NaCl and 66%KCl/34%NaCl throughout. Conclusion: Our findings suggest that the taste of the 50%KCl salt substitute would be well tolerated by South African adults, most of which could not visually differentiate between this salt substitute and common salt.Item Cost-effectiveness of a complex continuum of care intervention targeting women and children: protocol for an economic evaluation of the Bukhali trial in South Africa(BMJ Publishing Group, 2024) Norris, Shane A.; Palmer, Tom; Granados, Rolando Leiva; Draper, Catherine; Batura, NehaIntroduction: As nearly two-thirds of women presenting at their first antenatal visit are either overweight or obese in urban South Africa, the preconception period is an opportunity to optimise health and offset transgenerational risk of both obesity and non-communicable diseases. This protocol describes the planned economic evaluation of an individually randomised controlled trial of a complex continuum of care intervention targeting women and children in Soweto, South Africa (Bukhali trial). Methods and analysis: The economic evaluation of the Bukhali trial will be conducted as a within-trial analysis from both provider and societal perspectives. Incremental costs and health outcomes of the continuum of care intervention will be compared with standard care. The economic impact on implementing agencies (programme costs), healthcare providers, participants and their households will be estimated. Incremental cost-effectiveness ratios (ICERs) will be calculated in terms of cost per case of child adiposity at age years averted. Additionally, ICERs will also be reported in terms of cost per quality-adjusted life year gained. If Bukhali demonstrates effectiveness, we will employ a decision analytical model to examine the cost-effectiveness of the intervention over a child’s lifetime. A Markov model will be used to estimate long-term health benefits, healthcare costs and cost-effectiveness. Probabilistic sensitivity analyses will be conducted to explore uncertainty and ensure robust results. An analysis will be conducted to assess the equity impact of the intervention, by comparing intervention impact within quintiles of socioeconomic status. Ethics and dissemination: The Bukhali trial economic evaluation has ethical approval from the Human Ethics Research Committee of the University of the Witwatersrand, Johannesburg, South Africa (M240162). The results of the economic evaluation will be disseminated in a peer-reviewed journal and presented at a relevant international conference.Item Cultureconfirmed neonatal bloodstream infections and meningitis in South Africa 201419 a crosssectional studyMashau, Rudzani C.; Meiring, Susan ; Dramowski, Angela; Magobo, Rindidzani E.; Quan, Vanessa C. ; Von Gottberg, Anne ; Cohen, Cheryl ; Velaphi, Sithembiso ; Govender, Nelesh; Perovic, OlgaBackground: Few population-level estimates of invasive neonatal infections have been reported from sub-Saharan Africa. We estimated the national incidence risk, aetiology, and pathogen antimicrobial susceptibility for cultureconfirmed neonatal bloodstream infections and meningitis in South Africa. Methods: We conducted a cross-sectional study of neonates (<28 days of life) admitted to neonatal or paediatric wards of 256 public sector health facilities in South Africa during 2014–19. Diagnostic pathology records from Jan 1, 2014, to Dec 31, 2019, were extracted from a national pathology data warehouse. A case was defined as a neonate with at least one positive blood or cerebrospinal fluid culture during a 14-day period. Incidence risk was calculated using annual numbers of registered livebirths. Among the causative pathogens identified, we calculated the proportion of cases attributed to each of them, as well as the rates of antibiotic susceptibility of Gram-positive and Gram-negative bacteria. Findings: Among 43 438 records of positive cultures, there were 37 631 incident cases of neonatal infection with at least one pathogen isolated. The overall incidence risk of culture-confirmed infections was 6·0 per 1000 livebirths (95% CI 6·0–6·1). The incidence risk of late-onset sepsis (days 3–27 of life) was 4·9 per 1000 livebirths (4·9–5·0) and that of early-onset sepsis (days 0–2 of life) was 1·1 per 1000 livebirths (1·1–1·1); risk ratio 4·4 (95% CI 4·3–4·5). The cause of infection differed by syndrome, timing of infection onset, facility, and province, although Klebsiella pneumoniae (26%), Acinetobacter baumannii (13%), and Staphylococcus aureus (12%) were the dominant pathogens overall. Gram-negative bacteria had declining susceptibility to most antibiotics over the study period. Interpretation We found a high incidence risk of late-onset sepsis with provincial variations, predominance of K pneumoniae, and declining antibiotic susceptibility among Gram-negative bacteria. This national surveillance in an upper-middle-income country provides a baseline burden of neonatal infections against which the impact of future clinical and public health interventions can be measured.Item Explainable early prediction of gestational diabetes biomarkers by combining medical background and wearable devices: a pilot study with a cohort group in South Africa(Institute of Electrical and Electronics Engineers, 2024) Norris, Shane; Kolozali, Sefki; White, Sara L.; Fasli, Maria; van Heerden, AlastairThis study aims to explore the potential of Internet of Things (IoT) devices and explainable Artificial Intelligence (AI) techniques in predicting biomarker values associated with GDM when measured 13–16 weeks prior to diagnosis. We developed a system that forecasts biomarkers such as LDL, HDL, triglycerides, cholesterol, HbA1c, and results from the Oral Glucose Tolerance Test (OGTT) including fasting glucose, 1-hour, and 2-hour postload glucose values. These biomarker values are predicted based on sensory measurements collected around week 12 of pregnancy, including continuous glucose levels, short physical movement recordings, and medical background information. To the best of our knowledge, this is the first study to forecast GDM-associated biomarker values 13 to 16 weeks prior to the GDM screening test, using continuous glucose monitoring devices, a wristband for activity detection, and medical background data. We applied machine learning models, specifically Decision Tree and Random Forest Regressors, along with Coupled-Matrix Tensor Factorisation (CMTF) and Elastic Net techniques, examining all possible combinations of these methods across different data modalities. The results demonstrated good performance for most biomarkers. On average, the models achieved Mean Squared Error (MSE) between 0.29 and 0.42 and Mean Absolute Error (MAE) between 0.23 and 0.45 for biomarkers like HDL, LDL, cholesterol, and HbA1c. For the OGTT glucose values, the average MSE ranged from 0.95 to 2.44, and the average MAE ranged from 0.72 to 0.91. Additionally, the utilisation of CMTF with Alternating Least Squares technique yielded slightly better results (0.16 MSE and 0.07 MAE on average) compared to the well-known Elastic Net feature selection technique. While our study was conducted with a limited cohort in South Africa, our findings offer promising indications regarding the potential for predicting biomarker values in pregnant women through the integration of wearable devices and medical background data in the analysis. Nevertheless, further validation on a larger, more diverse cohort is imperative to substantiate these encouraging results.Item Final 192-week efficacy and safety results of the ADVANCE Trial, comparing 3 first-line antiretroviral regimens(Oxford University Press, 2024-01) Norris, Shane; Sokhela, Simiso; Venter, Willem D. F.; Bosch, Bronwyn; Woods, Joana; McCann, Kaitlyn; Akpomiemie, Godspower; Chandiwana, Nomathemba; Mashabane, Nkuli; Tembo, Angela; Simmons, Bryony; Lalla-Edward, Samanta; Siedner, Mark J.; Sinxadi, Phumla; Hermans, Lucas; Fairlie, Lee; Vos, Alinda; Abrams, Elaine; Manne-Goehler, Jennifer M.; Moorhouse, Michelle; Clayden, Polly; Qavi, Ambar; Chersich, Matthew; Masenya, Masebole; Arulappan, Natasha; Hill, AndrewBackground: ADVANCE compared 3 World Health Organization–recommended first-line regimens in participants with HIV who were antiretroviral naive. Methods: This randomized, open-label, noninferiority trial enrolled participants living with HIV with no antiretroviral exposure in the previous 6 months to 1 of the following arms: tenofovir alafenamide (TAF) / emtreicitabine (FTC) + dolutegravir (DTG) (2 tablets), tenofovir disoproxil fumarate (TDF) / FTC + DTG (2 tablets), or a fixed-dose combination of TDF / FTC / efavirenz (EFV) (1 tablet). We report the final safety and efficacy data up to 192 weeks. Results: Repeat consent from the original 351 participants randomized to each arm was obtained from 230 participants (66%) in the TAF/FTC + DTG arm, 209 (60%) in the TDF/FTC + DTG arm, and 183 (52%) in the TDF/FTC/EFV arm. At 192 weeks, 213 (61%) of the original 351 participants in the TAF/FTC + DTG arm, 195 (56%) in the TDF/FTC + DTG arm, and 172 (49%) in the TDF/FTC/EFV arm had confirmed RNA <50 copies/mL, with low virologic failure in all groups and no significant integrase inhibitor mutations in any arm. Mean weight gain was 8.9 kg (SD, 7.1) in the TAF/FTC + DTG arm, 5.9 kg (SD, 7.1) in the TDF/FTC + DTG arm, and 3.2 kg (SD, 8.1) in the TDF/FTC/EFV arm at 192 weeks from baseline and was greatest among women, those taking TAF, and those with lower baseline CD4 counts. The weight trajectory slowed after week 96. There were few clinical events and minor laboratory changes and differences among arms after 96 weeks. There were no significant differences in treatment-emergent hypertension or pregnancy outcomes by arm. Conclusions: High viral suppression was seen across arms, with no resistance to DTG. Weight gain continued but slowed after 96 weeks, with few clinical events or laboratory changes.Item Food insecurity and coping strategies associate with higher risk of anxiety and depression among South African households with children(Cambridge University Press, 2024-04) Norris, Shane A.; Dlamini, Siphiwe N.; Mtintsilana, Asanda; Craig, Ashleigh; Mapanga, WitnessObjective: To investigate food insecurity and related coping strategies, and their associations with the risk of anxiety and depression, among South African households with children. Design: Nationally representative cross-sectional study. Tools for assessing food insecurity, coping strategies, risk of anxiety and depression were assessed from the Community Childhood Hunger Identification Project, Coping Strategies Index, Generalised Anxiety Disorder-7 and Patient Health Questionnaire-9, respectively. We used ordered logistic regression to test associations of food insecurity and coping strategies with the risk of anxiety and depression. Moderating effects of each coping strategy were tested in the associations of food insecurity with anxiety and depression. Setting: South Africa, post COVID-19 restrictions, May–June 2022. Participants: 1,774 adults, weighted to 20,955,234 households. Results: Food insecurity prevalence was 23·7 % among households with children. All coping strategies were used to some extent, but relying on less preferred and less expensive foods was the most used strategy (85·5 % of food-insecure households). Moving to a higher level of food insecurity was associated with >1·6 greater odds of being in a higher risk of anxiety and depression. Sending a household member to beg for food was the strongest associated factor (OR = 1·7, P < 0·001). All coping strategies partly moderated (lessened) the associations of food insecurity with a higher risk of anxiety and depression. Conclusions: Food insecurity among households with children was high following the COVID-19 pandemic. Collaborative efforts between government, private sector and civil society to eradicate food insecurity should prioritise poorer households with children, as these populations are the most vulnerable.Item Infant growth and body composition from birth to 24 months: are infants developing the same?(Springer Nature, 2024) Norris, Shane A.; Nyati, Lukhanyo H.; Murphy-Alford, Alexia; Lucas, Nishani; Santos, Ina S.; Costa, Caroline S.; Kuriyan, Rebecca; Wickranasinghe, V. Pujitha; Ariff, Shabina; Jayasinghe, Sisitha; Kurpad, Anura V.; Ismail, Leila Cheikh; Hills, Andrew P.BACKGROUND: Given the importance of infancy for establishing growth trajectories, with later-life health consequences, we investigated longitudinal body composition among infants from six economically and ethnically diverse countries. METHODS: We recruited mother-infant dyads using the WHO Multicenter Growth Reference Study criteria. We measured fat-free mass (FFM) in 1393 (49% female) infants from birth to 6 months of age (Australia, India, and South Africa; n = 468), 3–24 months of age (Brazil, Pakistan, South Africa, and Sri Lanka; n = 925), and derived fat mass (FM), fat mass index (FMI), and fat-free mass index (FFMI). Height-for-age (HAZ), weight-for-age (WAZ), and weight-for-length (WHZ) Z-scores were computed. Sex differences were assessed using a t-test, and country differences using a one-way analysis of covariance. We further compared subsamples of children with average (−0.25 > HAZ < +0.25), below-average (≤−0.25) and above-average (≥+0.25) HAZ. RESULTS: HAZ performed well between 0 and 6 months, but less so between 3 and 24 months. The stunting prevalence peaked at 10.3% for boys and 7.8% for girls, at 24 months. By 24 months, girls had greater FMI (10%) than boys. There were significant differences in FFM (both sexes in all countries) and FM (Brazilian boys, Pakistani and South African girls) by 24 months of age between infants with average, above-average, and below-average HAZ. CONCLUSION: In a multi-country sample representing more ideal maternal conditions, body composition was heterogeneous even among infants who exhibited ideal length. Having a mean HAZ close to the median of the WHO standard for length reduced FFM between-country heterogeneity but not FM, suggesting that other factors may influence adiposity.Item Integrated health system intervention aimed at reducing type 2 diabetes risk in women after gestational diabetes in South Africa (IINDIAGO): a randomised controlled trial protocol(BMJ Publishing Group, 2024) Norris, Shane A.; Zarowsky, Christina; Murphy, Katherine; Ware, Lisa Jayne; Lombard, Carl; Matjila, Mushi; Chivese, Tawanda; Muhwava, Lorrein Shamiso; Mutabazi, Jean Claude; Harbron, Janetta; Fairall, Lara R.; Lambert, Estelle; Levitt, NaomiIntroduction South Africa has a high prevalence of gestational diabetes mellitus (GDM; 15%) and many of these women (48%) progress to type 2 diabetes mellitus (T2DM) within 5 years post partum. A significant proportion (47%) of the women are not aware of their diabetes status after the index pregnancy, which may be in part to low postnatal diabetes screening rates. Therefore, we aim to evaluate a intervention that reduces the subsequent risk of developing T2DM among women with recent GDM. Our objectives are fourfold: (1) compare the completion of the nationally recommended 6-week postpartum oral glucose tolerance test (OGTT) between intervention and control groups; (2) compare the diabetes risk reduction between control and intervention groups at 12 months’ post partum; (3) assess the process of implementation; and (4) assess the cost-effectiveness of the proposed intervention package. Methods and analyses Convergent parallel mixed methods study with the main component being a pragmatic, 2-arm individually randomised controlled trial, which will be carried out at five major referral centres and up to 26 well-baby clinics in the Western Cape and Gauteng provinces of South Africa. Participants (n=370) with GDM (with no prior history of either type 1 or type 2 diabetes) will be recruited into the study at 24–36 weeks’ gestational age, at which stage first data collection will take place. Subsequent data collection will take place at 6–8 weeks after delivery and again at 12 months. The primary outcome for the trial is twofold: first, the completion of the recommended 2-hour OGTT at the well-baby clinics 6–8 weeks post partum, and second, a composite diabetes risk reduction indicator at 12 months. Process evaluation will assess fidelity, acceptability, and dose of the intervention. Ethics and dissemination Ethics approval has been granted from University of Cape Town (829/2016), University of the Witwatersrand, Johannesburg (M170228), University of Stellenbosch (N17/04/032) and the University of Montreal (2019-794). The results of the trial will be disseminated through publication in peerreviewed journals and presentations to key South African Government stakeholders and health service providers. Protocol version 1 December 2022 (version #2). Any protocol amendments will be communicated to investigators, Human Ethics Research Committees, trial participants, and trial registries. Trial registration number PAN African Clinical Trials Registry (https://pactr.samrc.ac.za) on 11 June 2018 (identifier PACTR201805003336174).Item Locked down impact of covid 19 restrictions on trauma presentations to the emergency departmentVenter, Anica; Lewis, Carolyn; Saffy, Patricia; Chadinha, LouisBackground: COVID-19 was recognised as a global pandemic on 11 March 2020. In South Africa (SA), a nationwide lockdown was implemented at midnight on 26 March to prepare for the predicted surge and slow the spread of the virus. Objectives: To compare the volume and type of presentations of trauma secondary to interpersonal violence and road traffic collisions (RTCs) during two 5-month periods, from February to June 2019 and 2020, in the emergency department (ED) of an academic tertiary hospital in Gauteng Province, SA. In 2020, February - June included the lockdown period. Methods: An observational retrospective audit of the patient register at the Helen Joseph Hospital ED was conducted, comparing the number of trauma presentations secondary to interpersonal violence (assaults with gunshot wounds, general assaults including mob assaults, assaults with stab wounds) and RTC presentations between February and June 2019 and 2020. Results: A total of 4 300 trauma presentations secondary to interpersonal violence and RTCs were noted in the 5-month period February - June 2019, as opposed to 3 239 presentations in February - June 2020 (25% decline). A 40% decline in the number of RTCs, from 1 704 in February - June 2019 to 1 026 in the corresponding period for 2020, was noted and found to be statistically significant (p=0.03). Declines in the volume of trauma cases secondary to interpersonal violence and of overall trauma cases were only directional in favour of 2020, but not statistically significant. Conclusions: The volume of trauma presentations secondary to interpersonal violence and RTCs in the Helen Joseph Hospital ED decreased during the lockdown period. The decline in the volume of RTCs was statistically significant, but declines in the volume of trauma presentations secondary to interpersonal violence and in the volume of overall trauma presentations were not.Item Osteogenic competence and potency of the bone induction principle inductive substrates that initiate bone formation by autoinductionRipamonti, Ugo; Duarte, Raquel ; Ferretti, Carlo ; Reddi, H.The de novo induction of bone has always been a fascinating phenomenon, keeping skeletal reconstructionists and cellular developmental biologists continuously engaged to finally provide a molecular and cellular approach to the induction of bone formation. A significant advancement was made by the purification and cloning of the human recombinant bone morphogenetic proteins, members of the transforming growth factor-b supergene family. Human bone morphogenetic proteins are powerful inducers of bone in animal models including nonhuman primates. Translation in clinical contexts has however, proven to be surprisingly difficult. This review also describes the significant induction of bone formation by the human transforming growth factor-b3 when implanted in heterotopic intramuscular sites of the Chacma baboon Papio ursinus. Large mandibular defects implanted with 250mg human transforming growth factor-b3 in human patients showed significant osteoinduction; however, the induction of bone was comparatively less than the induction of bone in P ursinus once again highlighting the conundrum of human osteoinduction: is the bone induction principle failing clinical translation?Item SHBG, free testosterone, and Type 2 Diabetes risk in middle-aged African men: a longitudinal study(Oxford University Press, 2024) Norris, Shane; Seipone, Ikanyeng D.; Mendham, Amy E.; Storbeck, Karl-Heinz; Oestlund, Imken; Kufe, Clement N.; Chikowore, Tinashe; Masemola, Maphoko; Crowther, Nigel J.; Kengne, Andre Pascal; Olsson, Tommy; Brown, Todd; Micklesfield, Lisa K.; Goedecke, Julia H.Objectives: To investigate longitudinal changes in SHBG and free testosterone (free T) levels among Black middle-aged African men, with and without coexistent HIV, and explore associations with incident dysglycaemia and measures of glucose metabolism. Design: This longitudinal study enrolled 407 Black South African middle-aged men, comprising primarily 322 men living without HIV (MLWOH) and 85 men living with HIV (MLWH), with normal fasting glucose at enrollment. Follow-up assessments were conducted after 3.1 ± 1.5 years. Methods: At baseline and follow-up, SHBG, albumin, and total testosterone were measured and free T was calculated. An oral glucose tolerance test at follow-up determined dysglycaemia (impaired fasting glucose, impaired glucose tolerance, type 2 diabetes) and glucose metabolism parameters including insulin sensitivity (Matsuda index), insulin resistance (homeostasis model assessment of insulin resistance), and beta(β)- cell function (disposition index). The primary analysis focussed on MLWOH, with a subanalysis on MLWH to explore whether associations in MLWOH differed from MLWH. Results: The prevalence of dysglycaemia at follow-up was 17% (n = 55) in MLWOH. Higher baseline SHBG was associated with a lower risk of incident dysglycaemia (odds ratio 0.966; 95% confidence interval 0.945-0.987) and positively associated with insulin sensitivity (β = 0.124, P < .001) and β-cell function (β = 0.194, P = .001) at follow-up. Free T did not predict dysglycaemia. In MLWH, dysglycaemia prevalence at follow-up was 12% (n = 10). Neither baseline SHBG nor free T were associated with incident dysglycaemia and glucose metabolism parameters in MLWH. Conclusion: SHBG levels predict the development of dysglycaemia in middle-aged African men but do not exhibit the same predictive value in MLWH.Item The role of a community health worker‑delivered preconception and pregnancy intervention in achieving a more positive pregnancy experience: the Bukhali trial in Soweto, South Africa(BMC, 2024) Norris, Shane A.; Soepnel, Larske M.; Mabetha, Khuthala; Motlhatlhedi, Molebogeng; Nkosi, Nokuthula; Klingberg, Sonja; Lye, Stephen; Draper, Catherine E.Background: A patient-centered, human-rights based approach to maternal care moves past merely reducing maternal mortality and morbidity, towards achieving a positive pregnancy experience. When evaluating an intervention, particularly in the context of the complex challenges facing maternal care in South Africa, it is therefore important to understand how intervention components are experienced by women. We aimed to qualitatively explore (i) factors influencing the pregnancy and postpartum experience amongst young women in Soweto, South Africa, and (ii) the influence of Bukhali, a preconception, pregnancy, and early childhood intervention delivered by community health workers (CHWs), on these experiences. Methods: Semi-structured, in-depth interviews were conducted with 15 purposively sampled participants. Participants were 18–28-year-old women who (i) were enrolled in the intervention arm of the Bukhali randomized controlled trial; (ii) were pregnant and delivered a child while being enrolled in the trial; and (iii) had at least one previous pregnancy prior to participation in the trial. Thematic analysis, informed by the positive pregnancy experiences framework and drawing on a codebook analysis approach, was used. Results: The themes influencing participants’ pregnancy experiences (aim 1) were participants’ feelings about being pregnant, the responsibilities of motherhood, physical and mental health challenges, unstable social support and traumatic experiences, and the pressures of socioeconomic circumstances. In terms of how support, information, and care practices influenced these factors (aim 2), four themes were generated: acceptance and mother/child bonding, growing and adapting in their role as mothers, receiving tools for their health, and having ways to cope in difficult circumstances. These processes were found to be complementary and closely linked to participant context and needs. Conclusion: Our findings suggest that, among women aged 18–28, a CHW-delivered intervention combining support, information, and care practices has the potential to positively influence women’s pregnancy experience in South Africa. In particular, emotional support and relevant information were key to better meeting participant needs. These findings can help define critical elements of CHW roles in maternal care and highlight the importance of patient centred solutions to challenges within antenatal care.