Browsing by Author "Norris, Shane"

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    Cognitive and motor development in 3 to 6 year old children born to mothers with Hyperglycaemia first detected in pregnancy in an urban African population
    Soepnel, Larske ; Nicolaou, Veronique ; Draper, Catherine ; Levitt, N. ; Klipstein-Grobusch, Kerstin ; Norris, Shane
    Objectives: 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.
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    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.
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    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, Andrew
    Background: 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.
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    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.
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    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.