School of Clinical Medicine (Journal Articles)

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Predictors of switch to and early outcomes on third-line antiretroviral therapy at a large public-sector clinic in Johannesburg, South Africa
(BMC, 2018) Evans, Denise; Hirasen, Kamban; Berhanu, Rebecca; Malete, Given; Ive, Prudence; Spencer, David; Badal‑Faesen, Sharlaa; Sanne, Ian M.; Fox, Matthew P.
Background: While efficacy data exist, there are limited data on the outcomes of patients on third-line antiretroviral therapy (ART) in sub-Saharan Africa in actual practice. Being able to identify predictors of switch to third-line ART will be essential for planning for future need. We identify predictors of switch to third-line ART among patients with significant viraemia on a protease inhibitor (PI)-based second-line ART regimen. Additionally, we describe characteristics of all patients on third-line at a large public sector HIV clinic and present their early outcomes. Methods: Retrospective analysis of adults (≥ 18 years) on a PI-based second-line ART regimen at Themba Lethu Clinic, Johannesburg, South Africa as of 01 August 2012, when third-line treatment became available in South Africa, with significant viraemia on second-line ART (defined as at least one viral load ≥ 1000 copies/mL on second-line ART after 01 August 2012) to identify predictors of switch to third-line (determined by genotype resistance testing). Third line ART was defined as a regimen containing etravirine, raltegravir or ritonavir boosted darunavir, between August 2012 and January 2016. To assess predictors of switch to third-line ART we used Cox proportional hazards regression among those with significant viraemia on second-line ART after 01 August 2012. Then among all patients on third-line ART we describe viral load suppression, defined as a viral load < 400 copies/mL, after starting third-line ART. Results: Among 719 patients in care and on second-line ART as of August 2012 (with at least one viral load ≥ 1000 copies/mL after 01 August 2012), 36 (5.0% over a median time of 54 months) switched to third-line. Time on second-line therapy (≥ 96 vs. < 96 weeks) (adjusted Hazard Ratio (aHR): 2.53 95% CI 1.03–6.22) and never reaching virologic suppression while on second-line ART (aHR: 3.37 95% CI 1.47–7.73) were identified as predictors of switch. In a separate cohort of patients on third-line ART, 78.3% (47/60) and 83.3% (35/42) of those in care and with a viral load suppressed their viral load at 6 and 12 months, respectively. Conclusions: Our results show that the need for third-line is low (5%), but that patients’ who switch to third-line ART have good early treatment outcomes and are able to suppress their viral load. Adherence counselling and resistance testing should be prioritized for patients that are at risk of failure, in particular those who never suppress on second line and those who have been on PI-based regimen for extended periods.
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 Kim
Background: 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.
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, Sinead
Background: 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.
Influence of vitamin D receptor polymorphisms on biochemical markers of mineral bone disorders in South African patients with chronic kidney disease
(2018-02) Waziri, Bala; Dix-Peek, Therese; Dickens, Caroline; Duarte, Raquel; Naicker, Saraladevi
Background: It remains unclear whether genetic factors may explain the reported variation in the levels of biochemical markers of chronic kidney disease mineral and bone disorders (CKD- MBD) across ethnic groups. Therefore, the aim of this study was to examine the influence of vitamin D receptor (VDR) polymorphisms on secondary hyperparathyroidism and its association with vitamin D levels in black and white South African study participants. Methods: This was a cross sectional study involving 272 CKD stage 3- 5D patients and 90 healthy controls. The four major VDR polymorphisms (Bsm 1, Fok 1, Taq 1, and Apa1) were genotyped using the polymerase chain reaction- restriction fragment length polymorphism (PCR –RFLP) method. In addition, biochemical markers of CKD-MBD were measured to determine their associations with the four VDR polymorphisms. Results: With the exception of Taq I polymorphism, the distribution of the VDR polymorphisms differed significantly between blacks and whites. In hemodialysis patients, the Bb genotype was significantly associated with moderate secondary hyperparathyroidism (OR, 3.88; 95 CI 1.13–13.25, p = 0.03) and severe hyperparathyroidism (OR, 2.54; 95 CI 1.08–5.96, p = 0.03). This was consistent with the observed higher levels of median parathyroid hormone, fibroblast growth factor 23 and mean phosphate in patients with Bb genotype. This candidate risk genotype (Bb) was over represented in blacks compared to whites (71.0% versus 55.6%, p < 0.0001). In an unadjusted regression model, FokFf genotype was found to be significantly associated with the risk of developing severe vitamin D deficiency < 15 ng/ml (OR, 1.89; 95 CI 1.17–3.07, p = 0.01). Conclusion: The VDR Bb genotype is an independent predictor of developing secondary hyperparathyroidism in patients with end stage kidney disease. In addition, study participants with FokFf genotype are at increased of developing severe 25 -hydroxyvitamin D [25(OH)D] deficiency.
The presence of occipital hair in the pilonidal sinus cavity—a triple approach to proof
(Springer, 2018-02) Doll, Dietrich; Bosche, F.; Hauser, A.; Moersdorf, P.; Sinicina, I.; Grunwald, J.; Reckel, F.; Luedi, M. M.
Purpose: Hair in the pilonidal sinus is not growing within the sinus cavity, as hair follicles are not present there. Not few pilonidal patients do not have intergluteal hair, which is said to be the causative agent of folliculitis and pilonidal genesis. So, what is the real source of the hair forming the typical pilonidal hair nest? Methods: A trifold approach was used: First, axial hair strength testing of pilonidal hair and body hair harvested from head, lower back (glabella sacralis), and cranial third of intergluteal fold. Hair strength match was compared clinically. Second, comparative morphological examination by expert forensic biologist of hair from sinus and dorsal body hair. Third, statistical Bayesian classification of every single sinus hair based on its strength was done to determine the most probable region of origin. Results: Using clinical hair strength comparison, in 13/20 patients, head hair is the stiffest hair, followed by intergluteal hair. Only in 6/20 patients, this is the case with hair from the glabella sacralis. According to comparative morphological comparison, a minimum of 5 of 13 hair nests with possible hair allocation examined contain hair from the occiput. In 5/18 nests, hair could not be determined to a specific location though. Statistical classification with correction for multiple testing shows that 2 nests have hair samples that are at least 100 times more probable to originate from head or lower back than from intergluteal fold. Conclusion: We saw our null hypothesis that hair in the sinus cavity is from the intergluteal region^ rejected by each of three different approaches. There is strong evidence that occipital hair is present regularly in pilonidal sinus nests. We should start thinking of occipital hair as an important hair source for the development of the pilonidal hair nest.
Neurodevelopmental assessment of HIV-exposed uninfected and early-treated HIV-infected children: study protocol
(BMC, 2018-04) Strehlau, Renate; van Aswegen, Tamryn; Potterton, Joanne
Objective: Sub-Saharan Africa has the highest prevalence of children at risk of not achieving their developmental potential, attributable largely to the human immunodeficiency virus (HIV) pandemic coupled with negative environmental factors. Childhood developmental stimulation programmes can mitigate adverse outcomes. Methods: Neonates testing HIV positive at birth will be initiated on antiretroviral treatment (ART) and receive an age appropriate stimulation program, updated at 3 monthly intervals through the first year of life. Neurodevelopment at 12 months of age will be assessed using the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III). Outcomes will be compared with HIV-infected and HIV-exposed uninfected children (HEU) not having received the stimulatory intervention. Associations between neurodevelopmental outcomes, environmental factors, and parental stress will be investigated. The study will take place at a single site in Johannesburg, South Africa. This non-randomised controlled intervention study, with a single non-blinded comparative intervention group, aims to investigate whether an early childhood stimulation programme used in conjunction with ART initiated at birth can positively impact neurodevelopmental outcomes at 1 year of age in children infected with HIV.
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, Immo
Background: 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.
Improving poor outcomes of children with Biliary Atresia in South Africa by early referral to centralized units
(Wolters Kluwer., 2021) van der Schyff, Francisca; Terblanche, Alberta J.; Botha, Jean F.
Objectives: Biliary atresia (BA) is a progressive fibrosing cholangiopathy of infancy, the most common cause of cholestatic jaundice in infants and the top indication for liver transplantation in children. Kasai portoenterostomy (KPE) when successful may delay the requirement for liver transplantation, which in the majority offers the only cure. Good outcomes demand early surgical intervention, appropriate management of liver cirrhosis, and in most cases, liver transplantation. These parameters were audited of children with BA treated at the Steve Biko Academic Hospital (SBAH) in Pretoria, South Africa. Methods: All children with BA who were managed at SBAH between June 2007 and July 2018 were included. Parameters measured centered on patient demographics, timing of referral and surgical intervention, immediate and long-term outcomes of surgery, and follow-up management. Results: Of 104 children treated, 94 (90%) were KPE naive. Only 23/86 (26%) of children were referred before 60 days of life and 42/86 (49%) after 120 days. Median time to surgical assessment and surgery was 4 (IQR 1–70) and 5 (IQR 1–27) days post presentation, respectively. The median age at KPE was 91 days (IQR 28–165), with only 4/41 (12%) of KPEs performed before 60 days of life. Of those with recorded outcomes, 12/33 (36%) achieved resolution of jaundice. Only a third of the cohort were referred for transplantation. Conclusion: Children with BA have poor outcomes in the public health sector in South Africa. Late referrals, delayed diagnostics, advanced age at KPE with low drainage rates, poor follow–up, and low transplant rates account for low survival. Early referral to units offering expert intervention at all stages of care, including transplantation, would offer the best outcomes.
Integration of nutrition support using the FIGO nutrition checklist in the Bukhali trial: a dietitian’s perspective
(National Inquiry Services Centre (NISC) & Taylor and Francis Group, 2023) Norris, Shane A.; Mogashoa, Lethabo; Mabetha, Khuthala; Soepnel, Larske; Draper, Catherine E.
The burden of malnutrition experienced globally, coupled with the increasing rate of micronutrient deficiencies, compromises the health and well-being of women during their reproductive years. Obesity places young South African women at particular risk during pregnancy, and increases obesity risk for their offspring. To address these risks, the Bukhali trial is being implemented in Soweto, South Africa with 18–28-year-old women, as part of the Healthy Lifestyle Trajectory Initiative. A dietitian is part of the Bukhali intervention team (community health workers) to provide nutritional support for overweight/ obese trial participants, making use of the International Federation of Gynaecology and Obstetrics (FIGO) Nutrition Checklist. This paper reflects on the experiences and lessons learned by the Bukhali dietitian, including the use of the FIGO Nutrition Checklist and Healthy Conversation Skills to facilitate conversations about making healthy dietary behaviour changes. Identified challenges that influence nutrition and behaviour are discussed, including lack of food affordability, cultural and social influences on healthy food choices, unsupportive environments and food insecurity. Strategies to optimise this nutritional support are also mentioned. The Bukhali trial is showing that introducing additional nutrition support by a dietitian for at-risk participants has the potential to encourage young women to prioritise nutrition and health, even in the midst of contextual challenges to both nutrition and health.
Navigating relationship dynamics, pregnancy and fatherhood in the Bukhali trial: a qualitative study with men in Soweto, South Africa
(BMC, 2023) Norris, Shane A.; Draper, Catherine E.; Motlhatlhedi, Molebogeng; Mabasa, Jackson; Headman, Tshepang; Klingberg, Sonja; Pentecost, Michelle; Stephen J. Lye; Nyati, Lukhanyo H.
Background: South Africa has a complex range of historical, social, political, and economic factors that have shaped fatherhood. In the context of the Bukhali randomised controlled trial with young women in Soweto, South Africa, a qualitative study was conducted with the male partners of young women who had become pregnant during the trial. This exploratory study aimed to explore individual perceptions around relationship dynamics, their partner’s pregnancy, and fatherhood of partners of young women in Soweto, South Africa. Methods: Individual, in-depth interviews were conducted with male partners (fathers, n = 19, 25–46 years old) of Bukhali participants. A thematic approach was taken to the descriptive and exploratory process of analysis, and three final themes and subthemes were identified: (1) relationship dynamics (nature of relationship, relationship challenges); (2) pregnancy (feelings about the pregnancy, effect of the pregnancy on their relationship, providing support during pregnancy; and 3) fatherhood (view of fatherhood, roles of fathers, influences on views and motivation, challenges of fatherhood). Results: While most male participants were in a committed (“serious”) relationship with their female partner, less than half of them were cohabiting. Most reported that their partner’s pregnancy was not planned, and shared mixed feelings about the pregnancy (e.g., happy, excited, shocked, nervous), although their views about fatherhood were overwhelmingly positive. Many were concerned about how they would economically provide for their child and partner, particularly those who were unemployed. Participants identified both general and specific ways in which they provided support for their partner, e.g., being present, co-attending antenatal check-ups, providing material resources. For many, the most challenging aspect of fatherhood was having to provide financially. They seemed to understand the level of responsibility expected of them as a father, and that their involvement and presence related to love for and connection with their child. Participants’ responses indicated that there were some changes in the norms around fatherhood, suggesting that there is a possibility for a shift in the fatherhood narrative in their context. Conclusions: These findings suggest that the complex array of factors influencing fatherhood in South Africa continue to play out in this generation, although promising changes are evident.
Molecular and phenotypic characteristics of RSV infections in infants during two nirsevimab randomized clinical trials
(Nature Research, 2023) Madhi, Shabir A.; Ahani, Bahar; Tuffy, Kevin M.; Aksyuk, Anastasia A.; Wilkins, Deidre; Abram, Michael E.; Dagan, Ron; Domachowske, Joseph B.; Guest, Johnathan D.; Ji, Hong; Kushnir, Anna; Leach, Amanda; Mankad, Vaishali S.; Simões, Eric A. F.; Sparklin, Benjamin; Speer, Scott D.; Stanley, Ann Marie; Tabor, David E.; Hamrén, Ulrika Wählby; Kelly, Elizabeth J.; Villafana, Tonya
Nirsevimab is a monoclonal antibody that binds to the respiratory syncytial virus (RSV) fusion protein. During the Phase 2b (NCT02878330) and MELODY (NCT03979313) clinical trials, infants received one dose of nirsevimab or placebo before their first RSV season. In this pre-specified analysis, isolates from RSV infections were subtyped, sequenced and analyzed for nirsevimab binding site substitutions; subsequently, recombinant RSVs were engineered for microneutralization susceptibility testing. Here we show that the frequency of infections caused by subtypes A and B is similar across and within the two trials. In addition, RSV A had one and RSV B had 10 fusion protein substitutions occurring at >5% frequency. Notably, RSV B binding site substitutions were rare, except for the highly prevalent I206M:Q209R, which increases nirsevimab susceptibility; RSV B isolates from two participants had binding site substitutions that reduce nirsevimab susceptibility. Overall, >99% of isolates from the Phase 2b and MELODY trials retained susceptibility to nirsevimab.
Maternal perceptions of infant's body weight and childhood obesity in South Africa: a qualitative study in Soweto
(Wiley, 2023) Norris, Shane A.; Cohen, Emmanuel; Wrottesley, Stephanie V.; Prioreschi, Alessandra; Slemming, Wiedaad
From a socio-anthropological study focusing on maternal body weight perceptions and dietary practices towards infants living in Soweto (South Africa), we studied how lay sociocultural traits may lead to early childhood obesity. Most mothers tended to socially value and normalize fatness. This propensity led mothers, particularly older women at home, to adopt high-calorie feeding practices towards infants, although some mothers tended to question these lay norms. Further works must consider how lay (emic) sociocultural norms in African townships can contradict biomedical (etic) messages, conveying for the community thinness as the acceptable standard, and may expose infants to early obesity.
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.
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.
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, Ashleigh
This 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.
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, Alastair
This 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.
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, Stephen
Background: 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.
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, Neha
Introduction: 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.
Variability of polygenic prediction for body mass index in Africa
(BioMed Central (BMC), 2024) Norris, Shane A.; Chikowore, Tinashe; Läll, Kristi; Micklesfield, Lisa K.; Lombard, Zane; Goedecke, Julia H.; Fatumo, Segun; Magi, Reedik; Ramsay, Michele; Franks, Paul W.; Pare, Guillaume; Morris, Andrew P.
Background: Polygenic prediction studies in continental Africans are scarce. Africa’s genetic and environmental diversity pose a challenge that limits the generalizability of polygenic risk scores (PRS) for body mass index (BMI) within the continent. Studies to understand the factors that affect PRS variability within Africa are required. Methods: Using the first multi-ancestry genome-wide association study (GWAS) meta-analysis for BMI involving continental Africans, we derived a multi-ancestry PRS and compared its performance to a European ancestry-specific PRS in continental Africans (AWI-Gen study) and a European cohort (Estonian Biobank). We then evaluated the factors affecting the performance of the PRS in Africans which included fine-mapping resolution, allele frequencies, linkage disequilibrium patterns, and PRS-environment interactions. Results: Polygenic prediction of BMI in continental Africans is poor compared to that in European ancestry individuals. However, we show that the multi-ancestry PRS is more predictive than the European ancestry-specific PRS due to its improved fine-mapping resolution. We noted regional variation in polygenic prediction across Africa’s East, South, and West regions, which was driven by a complex interplay of the PRS with environmental factors, such as physical activity, smoking, alcohol intake, and socioeconomic status. Conclusions: Our findings highlight the role of gene-environment interactions in PRS prediction variability in Africa. PRS methods that correct for these interactions, coupled with the increased representation of Africans in GWAS, may improve PRS prediction in Africa.
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.