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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 Associations between nutrition knowledge and obesity-related attitudes and physical activity among young adults from Kenya, South Africa, and the United Kingdom(National Inquiry Services Centre (NISC) & Taylor and Francis Group, 2024) Norris, Shane A.; Dlamini, Siphiwe N.; Mtintsilana, Asanda; Mapanga, Witness; Craig, AshleighThis study’s aim was to test associations between nutrition knowledge and obesity-related attitudes and physical activity (PA) among 3000 18–35-year-old men and women from Kenya, South Africa (SA), and the United Kingdom (UK).Methods: A cross-sectional online survey was conducted in April 2022. To estimate nutrition knowledge, dietary recommendation knowledge score was computed using the standard General Nutrition Knowledge questionnaire. Obesity-related attitudes were from the British Social Attitudes Survey. Self-reported days of vigorous and moderate PAs and walking were used. Ordinal logistic regression was employed to test all associations, while adjusting for age group, gender and a household asset score. Using simple mediation, testing was also done to ascertain whether obesity-related attitudes mediated associations between nutrition knowledge and PA. Results: Consistently, better nutrition knowledge was associated with disagreeing that ‘There is no reason to worry about obesity’ (ORs ≥ 1.09), but lower odds of being against ‘Providing free weight management courses’ and ‘Creating/improving cycle paths and pavements to encourage PA’ (ORs ≤ 0.90). Better nutrition knowledge was also associated with higher vigorous PA in SA (OR = 1.09), and moderate PA (OR = 1.04) and walking (OR = 1.12) in the UK. In the combined sample, associations of nutrition knowledge with vigorous PA were fully mediated by believing that ‘Obesity results from not exercising enough’ (11.1% mediated). Likewise, associations of nutrition knowledge with moderate PA were fully mediated by attitude towards ‘Creating or improving cycle paths and pavements to encourage PA’ in the UK (38.9% mediated).Conclusions: Nutrition knowledge is associated with obesity-related attitudes and PA among young adults, but some relationships are country-specific. Interventions based on findings from high-income countries should be evaluated before being implemented in low-resource settings.Item Bone mineral density in midlife long-term users of hormonal contraception in South Africa: relationship with obesity and menopausal status(BMC, 2018-04) Beksinska, Mags E.; Smit, Jenni A.; Kleinschmidt, ImmoBackground: In South Africa, hormonal contraception is widely used in women over the age of 40 years. One of these methods and the most commonly used is depot-medroxyprogesterone acetate (DMPA) which has been found to have a negative effect on bone mass. Limited information is available on the effect of norethisterone enanthate (NET-EN) on bone mass, and combined oral contraceptives (COCs) have not been found to be associated with loss of bone mass. The aim of this study was to investigate bone mineral density (BMD) in pre and perimenopausal women (40–49 years) in relation to use of DMPA, NET-EN and COCs for at least 12 months preceding recruitment into the study and review associations with body mass index (BMI) and menopausal status. Methods: One hundred and twenty seven users of DMPA, 102 NET-EN users and 106 COC users were compared to 161 nonuser controls. Menopausal status was assessed, BMI and forearm BMD was measured at the distal radius using dual X-ray absorptiometry. Comparison analysis was conducted at baseline and 2.5 years. Results: There was no significant difference in BMD between the four contraceptive user groups (p = 0.26) with and without adjustment for age at baseline or at 2.5 years (p = 0.52). The BMD was found to be significantly associated with BMI (p = < 0.0001) with an increase of one unit of BMI translating to an increase of 0.0044 g/cm2 in radius BMD. Follicle stimulating hormone (FSH) level ≥ 25.8 mIU/mL was associated with a decrease of 0.017 g/cm2 in radius BMD relative to women with FSH < 25.8 mIU/mL. Significant interaction between FSH and BMI in their effect on BMD was observed (p = .006). Conclusion: This study found no evidence that long-term use of DMPA, NET-EN and COCs affects forearm BMD in this population at baseline or after 2.5 years of follow-up. This study also reports the complex relationship and significant interaction between FSH and BMI in their effect on BMD. BMD research in older women needs to ensure that women are assessed for menopausal status and BMI.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 Development and feasibility of a wearable infant wrist band for the objective measurement of physical activity using accelerometery(BMC, 2018) Prioreschi, Alessandra; Nappey, Thomas; Westgate, Kate; Olivier, Patrick; Brage, Soren; Micklesfield, Lisa KimBackground: It is important to be able to reliably and feasibly measure infant and toddler physical activity in order to determine adherence to current physical activity guidelines and effects on early life development, growth and health. This study aimed to describe the development of an infant wearable wrist-worn band for the measurement of physical activity; to determine the feasibility of the device data for observational measurement of physical activity and to determine the caregiver reported acceptability of the infant wearable wrist band. Methods: After various iterations of prototypes and piloting thereof, a final wearable band was designed to fit an Axivity AX3 monitor. Mother and infant/toddler (aged 3–24 months) pairs (n = 152) were recruited, and mothers were asked for their child to wear the band with enclosed monitor at all times for 1 week (minimum 3 days). Feasibility was assessed by determining technical reliability of the data, as well as wear time and compliance according to requirements for observational measurement. Acceptability was assessed via questionnaire. Results: Technical reliability of the Axivity AX3 monitors in this age group was good. After excluding days that did not have at least 15 h of wear time, only 2% of participants had less than three valid days of data remaining, and 4% of participants had no data (due to device loss or data loss). Therefore, 94% of participants were compliant, having three or more days of wear with at least 15 h of wear per day, thus providing enough valid data for observational measurement. The majority (60%) of mothers reported being “very happy” with the safety of the device, while only 8% were “a little worried”. A large majority (86%) of mothers stated that the band attracted attention from others, although this was mostly attributed to curiosity about the function of the band. Most (80%) of participants rated the comfort of the band as “comfortable”, and 10% rated it as “very comfortable”. Conclusions: The infant wearable band proved to be feasible and acceptable according to the criteria tested, and compliance wearing the band was good. We have therefore provided a replicable, comfortable and acceptable pearable band for the measurement of infant and toddler physical activity.Item Does engagement in HIV care affect screening diagnosis and control of noncommunicable diseases in sub-Saharan Africa: a systematic review and meta analysis(Springer , 2024-02) Kileel, E.; Zheng, Amy; Bor, Jacob; Fox, Matthew; Crowther, Nigel; George, Jaya; Khoza, Siyabonga; Rosen, Sydney; Venter, Willem; Raal, Frederick; Hibberd, Patricia; Brennan, AlanaLow- and middle-income countries are facing a growing burden of noncommunicable diseases (NCDs). Providing HIV treatment may provide opportunities to increase access to NCD services in under-resourced environments. We conducted a systematic review and meta-analysis to evaluate whether use of antiretroviral therapy (ART) was associated with increased screening, diagnosis, treatment, and control of diabetes, hypertension, chronic kidney disease, or cardiovascular disease among people living with HIV in sub-Saharan Africa (SSA). A comprehensive search of electronic literature databases for studies published between 01 January 2011 and 31 December 2022 yielded 26 studies, describing 13,570 PLWH in SSA, 61% of whom were receiving ART. Random effects models were used to calculate summary odds ratios (ORs) of the risk of diagnosis by ART status and corresponding 95% confidence intervals (95% CIs), where appropriate. ART use was associated with a small but imprecise increase in the odds of diabetes diagnosis (OR 1.07; 95% CI 0.71, 1.60) and an increase in the odds of hypertension diagnosis (OR 2.10, 95% CI 1.42, 3.09). We found minimal data on the association between ART use and screening, treatment, or control of NCDs. Despite a potentially higher NCD risk among PLWH and regional efforts to integrate NCD and HIV care, evidence to support effective care integration models is lacking.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 Impacts of heat exposure in utero on longterm health and social outcomes: a systematic review(BioMed Central (BMC), 2024) Norris, Shane; Brink, Nicholas; Lakhoo, Darshnika P.; Solarin, Ijeoma; Maimela, Gloria; von Dadelszen, Peter; Chersich, Matthew F.Background: Climate change, particularly global warming, is amongst the greatest threats to human health. While short-term effects of heat exposure in pregnancy, such as preterm birth, are well documented, long-term effects have received less attention. This review aims to systematically assess evidence on the long-term impacts on the foetus of heat exposure in utero. Methods: A search was conducted in August 2019 and updated in April 2023 in MEDLINE(PubMed). We included studies on the relationship of environmental heat exposure during pregnancy and any long-term outcomes. Risk of bias was assessed using tools developed by the Joanna-Briggs Institute, and the evidence was appraised using the GRADE approach. Synthesis without Meta-Analysis (SWiM) guidelines were used. Results: Eighteen thousand six hundred twenty one records were screened, with 29 studies included across six outcome groups. Studies were mostly conducted in high-income countries (n=16/25), in cooler climates. All studies were observational, with 17 cohort, 5 case-control and 8 cross-sectional studies. The timeline of the data is from 1913 to 2019, and individuals ranged in age from neonates to adults, and the elderly. Increasing heat exposure during pregnancy was associated with decreased earnings and lower educational attainment (n=4/6), as well as worsened cardiovascular (n=3/6), respiratory (n=3/3), psychiatric (n=7/12) and anthropometric (n=2/2) outcomes, possibly culminating in increased overall mortality (n=2/3). The effect on female infants was greater than on males in 8 of 9 studies differentiating by sex. The quality of evidence was low in respiratory and longevity outcome groups to very low in all others. Conclusions Increasing heat exposure was associated with a multitude of detrimental outcomes across diverse body systems. The biological pathways involved are yet to be elucidated, but could include epigenetic and developmental perturbations, through interactions with the placenta and inflammation. This highlights the need for further research into the long-term effects of heat exposure, biological pathways, and possible adaptation strategies in studies, particularly in neglected regions. Heat exposure in-utero has the potential to compound existing health and social inequalities. Poor study design of the included studies constrains the conclusions of this review, with heterogenous exposure measures and outcomes rendering comparisons across contexts/studies difficult.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.