School of Clinical Medicine (Journal Articles)

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    Lipid levels, insulin resistance and cardiovascular risk over 96 weeks of antiretroviral therapy: a randomised controlled trial comparing low-dose stavudine and tenofovir
    (BioMed Central, 2018-12) Vos, Alinda G.; Chersich, Matthew F.; Klipstein‑Grobusch, Kerstin; Zuithof, Peter; Moorhouse, Michelle A.; Lalla‑Edward, Samanta T.; Kambugu, Andrew; Kumarasamy, N.; Grobbee, Diederick E.; Barth, Roos E.; Venter, Willem D.
    Background: HIV infection and antiretroviral treatment are associated with changes in lipid levels, insulin resistance and risk of cardiovascular disease (CVD). We investigated these changes in the first 96 weeks of treatment with lowdose stavudine or tenofovir regimens. Methods: This is a secondary analysis of a double blind, randomised controlled trial performed in South-Africa, Uganda and India comparing low-dose stavudine (20 mg twice daily) with tenofovir in combination with efavirenz and lamivudine in antiretroviral-naïve adults (n = 1067) (Clinicaltrials.gov, NCT02670772). Over 96 weeks, data were collected on fasting lipids, glucose and insulin. Insulin resistance was assessed with the HOMA-IR index and 10-year CVD risk with the Framingham risk score (FRS). A generalized linear mixed model was used to estimate trends over time. Results: Participants were on average 35.3 years old, 57.6% female and 91.8% Black African. All lipid levels increased following treatment initiation, with the sharpest increase in the first 24 weeks of treatment. The increase in all lipid subcomponents over 96 weeks was higher among those in the stavudine than the tenofovir group. Insulin resistance increased steadily with no difference detected between study groups. FRS rose from 1.90% (1.84–1.98%) at baseline to 2.06 (1.98–2.15%) at week 96 for the total group, with no difference between treatment arms (p = 0.144). Lipid changes were more marked in Indian than African participants. Conclusion: Lipid levels increased in both groups, with low-dose stavudine resulting in a worse lipid profile compared to tenofovir. Insulin resistance increased, with no difference between regimens. CVD risk increased over time and tended to increase more in the group on stavudine. The low CVD risk across both arms argues against routine lipid and glucose monitoring in the absence of other CVD risk factors. In high risk patients, monitoring may only be appropriate at least a year after treatment initiation.
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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.