Mobile health (mHealth) interventions offer scalable support for adherence and self-management, yet their effects on health-related quality of life (HRQoL) among people living with HIV (PLWH) and comorbid hypertension remain unclear. We evaluated HRQoL outcomes using data from the MOPHADHIV trial, a 12-month short message service (SMS)-based randomized controlled trial conducted at four community health centres in Cape Town, South Africa. HRQoL was measured using the EuroQol 5-Dimension 5-Level (EQ-5D-5L) utility index (Ugandan value set) and the EuroQol Visual Analogue Scale (VAS) at baseline and 12 months. Between-group differences were assessed using two-sample t-tests and analysis of covariance (ANCOVA) models adjusting for baseline HRQoL and covariates. A total of 582 participants (279 control; 303 intervention) with complete HRQoL data at baseline and 12 months were included in the analysis. Baseline HRQoL was high and comparable across arms. At 12 months, EQ-5D-5L utility was slightly higher in the control arm (0.97 vs 0.95; mean difference 0.03; t = 2.66, p = 0.01), corresponding to a small effect size (Cohen’s d = 0.22). In adjusted models, intervention allocation was associated with a small reduction in EQ-5D-5L utility (β = − 0.02, p = 0.01; fully adjusted β = − 0.03, p < 0.01). VAS scores improved in both groups, with no significant between-arm differences. In this cohort of PLWH with hypertension, a 12-month SMS-based intervention did not improve HRQoL and was associated with a small reduction in EQ-5D-5L utility. High baseline HRQoL and limited sensitivity of EQ-5D-5L to HIV-related psychosocial domains may partly explain these findings.

Sickle cell disease (SCD) remains a major public health concern in sub-Saharan Africa (SSA), where approximately 200,000 newborns are affected annually. Without early diagnosis and access to care, up to 50% of these children may die before the age of five. Although newborn screening (NBS) programs have proven effective in improving survival, their implementation across Africa is constrained by logistical barriers associated with standard diagnostic methods such as isoelectric focusing (IEF), high-performance liquid chromatography (HPLC), and cellulose acetate electrophoresis. Dried blood spot point-of-care testing (DBS-POCT) offers a potentially scalable alternative due to its stability, simplicity, and suitability for centralized analysis. We evaluated the diagnostic accuracy of DBS-POCT using the HemoTypeSC test compared to both standard POCT and reference laboratory testing across 705 newborns (0-3 months old) in seven countries within the SickleInAfrica Consortium. DBS-POCT demonstrated high sensitivity and specificity for detecting HbAA and HbAS, moderate sensitivity for HbSS, and lower sensitivity for HbAC, with some variability across countries. In several countries, DBS-POCT outperformed standard POCT, particularly in detecting SCD subtypes. Our findings support the utility of DBS-POCT for expanding newborn screening programs in resource-limited settings.

The prevalence of type 2 diabetes is rising rapidly across sub-Saharan Africa; however, its epidemiology, clinical phenotypes, and underlying mechanisms remain insufficiently characterised. This first paper in a Series on diabetes in sub-Saharan Africa synthesises current evidence on the burden, distribution, and determinants of diabetes, including emerging phenotypes and the roles of early life adversity, psychosocial stress, and interactions with infectious disease. We also identify major gaps in surveillance systems, research capacity, prevention, and clinical management across the region. Sub-Saharan Africa is experiencing one of the fastest global increases in diabetes, with the highest proportion of undiagnosed cases and a projected steep rise in intermediate hyperglycaemia and diabetes by 2050. Urbanisation, ageing, obesity, and lifestyle transitions are major contributors; however, a substantial proportion of type 2 diabetes occurs in lean individuals (BMI <25 kg/m2), particularly in rural settings, suggesting distinct metabolic and developmental pathways not captured by models derived from high-income countries. Bidirectional interactions between diabetes and malaria, tuberculosis, HIV, or COVID-19 make disease trajectories complex. Persistent gaps in surveillance, a reliance on modelled estimates, low genomic representation, and constrained access to modern diabetes medications hinder progress. Strengthening health system capacity, improving data infrastructure, and investing in regionally driven research are essential to develop effective, context-specific interventions and advance precision medicine tailored to sub-Saharan African populations.

Hypertension is an increasingly common comorbidity among adults living with HIV in sub-Saharan Africa, yet data from routine HIV clinics in Cameroon remain limited. We examined factors associated with prevalent hypertension among adults receiving antiretroviral therapy (ART) at Yaoundé Central Hospital. In this cross-sectional study of 460 participants, hypertension (blood pressure ≥ 140/90 mmHg and/or current antihypertensive treatment) was present in 43.3%. Using robust Poisson regression, older age and obesity were independently associated with higher hypertension prevalence, and family history showed the strongest association (adjusted prevalence ratio 2.83). Cumulative ART duration was not independently associated after adjustment. Weekly fruit and vegetable intake was associated with lower hypertension prevalence, whereas salt/seasoning cube intake and most behavioural factors were not associated after adjustment. Restricted cubic spline analyses did not suggest non-linearity in the relationship between ART duration and hypertension. In this urban HIV care setting, hypertension clustered primarily with conventional cardiometabolic factors rather than time on ART. Integrating systematic blood pressure screening and standardised hypertension management within HIV services, alongside weight management and lifestyle counselling, may help reduce cardiovascular burden among people living with HIV.

Background Despite accounting for a substantial proportion of the global population and disease burden, African countries are underrepresented in randomized controlled trials (RCTs), including those informing cardiovascular (CV) care. Objectives In this study, we sought to quantify African representation in RCTs published from 2019 to 2024 in: 1) 5 leading general medical journals; and 2) 3 leading CV journals. Methods We conducted a systematic review of RCTs published from 2019 to 2024 in the British Medical Journal, the Journal of the American Medical Association, The Lancet, Nature Medicine, and the New England Journal of Medicine, and in Circulation, the European Heart Journal, and the Journal of the American College of Cardiology. Eligible studies included traditional, pragmatic, cluster, and stepped-wedge RCTs. African representation was assessed by trial scope (Africa-only vs multicontinental), country and regional participation, disease category, and African authorship. Results Among 2,138 RCTs published in leading general medical journals, only 83 (3.9%) were conducted exclusively in Africa, and 195 (9.1%) were multicontinental studies including at least 1 African site. In the CV journals, 2 out of 334 RCTs (0.6%) were conducted exclusively in Africa, and African sites were included in only 9 multicontinental trials (2.7%). South Africa accounted for the majority of Africa-based RCTs across both journal categories. Regionally, southern Africa predominated and central Africa was minimally represented. Trials published in general medical journals and conducted exclusively in Africa largely focused on infectious diseases (n = 63; 75.9%), with only 3 addressing cardiovascular disease (CVD). In contrast, Africa-including multicontinental trials more frequently investigated noncommunicable diseases, including CVD. African leadership was common in Africa-only trials but rare in multicontinental studies. Conclusions African countries are profoundly underrepresented in RCTs published in the world’s most influential medical and CV journals. Addressing this imbalance requires expanding African participation in global trials, investing in local research capacity, and promoting equitable leadership to strengthen the relevance and validity of clinical evidence. (Underrepresentation of African Countries in Randomized Controlled Trials: A Systematic Review of Leading General Medical and Cardiovascular Journals; CRD42024603157)

In the original publication [...].

Sickle cell disease (SCD) is one of the most prevalent monogenic disorders worldwide, with the highest burden in Africa, where ~75% of the 7.74 million global cases occur. Scientific progress in understanding its epidemiology, clinical heterogeneity, and treatment outcomes has been constrained by heterogeneous, non-standardized, and non-interoperable datasets that limit data integration and cross-country analyses. To address this, the Sickle Africa Data Coordinating Centre (SADaCC) was established as the data science hub of the SickleInAfrica consortium to support the development and expansion of Pan-African SCD registry. SADaCC now coordinates one of the largest patient-consented SCD datasets globally, with data from over 40 000 persons living with SCD in seven countries (Ghana, Mali, Nigeria, Tanzania, Uganda, Zambia, and Zimbabwe) within the Sickle Pan-African Research Consortium (SPARCo), as well as genomic data from SADaCC satellite sites in Cameroon, South Africa, and Malawi. The registry is built on FAIR-compliant architecture, the Sickle Cell Disease Ontology, and powered by a suite of digital platforms such as REDCap, NextCloud, RStudio, GitHub, Docker, and Jupyter. In partnership with SPARCo, SADaCC is also piloting a biobank that will link biospecimens with data in the registry to advance multi-omics research. Beyond infrastructure, SADaCC leads training and/or research in big data analytics, genomics, bioethics, implementation science, qualitative research, and psychosocial studies. Ethical, legal, and social considerations are embedded across all operations with emphasis on equitable intra-African collaboration and patient involvement in research. Looking ahead, SADaCC will integrate real-time data streams, AI-driven analytics, and multi-omics data to drive big data and genetic medicine research for SCD in Africa.

Our study investigated the association between transcription factor 7-like 2 (TCF7L2-rs7903146), angiotensin convertase enzyme (ACE-rs4646994), angiotensinogen (AGT-rs699), angiotensin II type 1 receptor (AGT1R-rs5186), fat mass and obesity-associated (FTO-rs17817499) and melanocortin 4 receptor (MC4R-rs17782313, rs12970134 and rs229616) single nucleotide polymorphisms (SNPs) with type 2 diabetes (T2D), obesity and hypertension in a Black South African population. This cross-sectional study involved 560 Black South Africans aged 25 to 74 years. Participant demographic and lifestyle characteristics were self-reported; anthropometry and blood pressures (BP) measured; oral glucose tolerance tests used to diagnose T2D; and SNPs genotyped by polymerase chain reaction. The Benjamini-Hochberg method was used to control for multiple hypothesis testing, using a significance threshold of 0.12. Using the median test, systolic BP was significantly higher in carriers of the G/G genotype of rs229616 within the MC4R gene compared to carriers of the G/A genotype (p = 0.006, p-FDR = 0.030). In the same gene, logistic regression analysis showed that carriers of the minor C/C genotype of the rs17782313 SNP had a significantly higher risk of hypertension (OR = 1.37, p = 0.023, p-FDR = 0.115) in the unadjusted model. However, the significance was attenuated after adjusting for age, gender and BMI (OR = 1.32, p = 0.084, p-FDR = 0.140). Moreover, carriers of the minor T/T genotype of the TCF7L2 rs7903146 SNP had a lower risk of T2D in the crude model (OR = 0.66, p = 0.043, p-FDR = 0.108) and after adjustment for age, gender and BMI (OR = 0.63, p = 0.041, p-FDR = 0.108). These findings remained significant after correction for multiple comparisons. TCF7L2-rs7903146 (C/C genotype) and MC4R-17,782,313 (C/C genotype) SNPs are potential genetic risk factors for T2D and hypertension, respectively, in the Black South African population. Replicating these findings and exploring the role played by these genetic variants in downstream molecular pathways could aid in risk stratification and facilitate personalized approaches to healthcare delivery.

INTRODUCTION:The burden of cardiometabolic diseases (CMDs) is rising in people with HIV (PWH). While extensive data exist on CMD prevalence in PWH receiving antiretroviral therapy (ART), comprehensive data on ART-naïve PWH are scarce. We aimed to estimate the global prevalence of hypertension, diabetes, obesity and dyslipidaemia among ART-naïve PWH and compare estimates with those on ART and HIV-negative populations. METHODS:This systematic review and meta-analysis included a search of PubMed-MEDLINE, CINAHL, SCOPUS, Academic Search Premier, Africa-Wide Information and Africa-Journals Online for original articles published up to June 2024. Cross-sectional, cohort and case-control studies providing baseline data on CMD prevalence were included. Studies had to include ART-naïve PWH aged ≥15 years. Two independent reviewers conducted studies screening, data extraction and methodological quality assessment. A random-effects meta-analysis with double arc-sine transformation was used for prevalence estimates. The study was registered with PROSPERO (CRD42021226001). RESULTS:We included 184 studies published between 2000 and 2024, involving a total of 424 629 participants. The global pooled prevalence among ART-naïve PWH was 14.2% (95% CI: 12.4-16.1) for hypertension, 3.6% (2.9-4.3) for diabetes, 11.5% (10.3-12.9) for body mass index-based obesity, 18.3% (12.7-24.6) for waist circumference-based obesity, 14.8% (12.1-17.8) for elevated total cholesterol, 17.6% (11.3-24.8) for elevated low-density lipoprotein cholesterol, 22.9% (19.3-26.7) for elevated triglycerides and 54.6% (48.2-61.0) for low high-density lipoprotein cholesterol, all with high heterogeneity. Significant regional variations in the prevalence of diabetes, obesity and dyslipidaemia were observed according to UNAIDS regions. DISCUSSION:We found a notable prevalence of CMDs in ART-naïve PWH, with significant regional variations in the prevalence of diabetes, obesity and dyslipidaemia. This highlights the need for targeted interventions and early screening to address the growing CMD burden among PWH. CONCLUSION:ART-naïve PWH face a considerable CMD burden, emphasizing the importance of early detection and management. Regional differences in CMD prevalence call for tailored public health strategies and integration of CMD prevention into HIV care protocols.

BACKGROUND:Data science methods can provide novel and pragmatic approaches for preventing and controlling non-communicable diseases (NCDs) in Africa. This study highlights current efforts, opportunities, and challenges in leveraging data science methods to accelerate and advance the prevention and control of NCDs in Africa. METHODS:We undertake a systematic review and gap analysis, as registered in PROSPERO (CRD42023406237). RESULTS:Our findings suggest several data science methods have been used in research across the four leading NCDs in Africa. However, limited information exists on their application to improve disease surveillance, risk factor identification and characterization, prevention, treatment, drug discovery and rehabilitation. Machine learning outperforms traditional statistical methods in improving risk stratification in most studies (80.8%) designed for the prevention and control of NCDs. Notwithstanding, most (76.0%) data science techniques for NCDs prevention and control remain in the exploratory research phase, with limited clinical or public health application and minimal impact on the African population. There are critical gaps along the continuum of data generation, data quality, method development, and validation, which may be attributed to inadequate funding, capacity development, policy shortcomings, and infrastructure deficits. Considerable gaps exist in intra-African collaboration, data sharing, and replication, which hinder the cross-cultural replication and applicability of data science methods for NCDs prevention and control in Africa. CONCLUSIONS:Multi-sectoral interventions that promote interdisciplinary capacity building, investment, and knowledge linkages, taking into account indigenous epistemologies, are needed to harness the enormous potential of data science to accelerate the prevention and control of NCDs in Africa.

Hypertension is a frequent comorbidity among people living with HIV (PLHIV) in sub-Saharan Africa, but analytical data from routine HIV clinics in Cameroon remain limited. This study assessed factors associated with prevalent hypertension among adults receiving antiretroviral therapy (ART) at an urban HIV clinic in Yaounde, Cameroon. We conducted a cross-sectional study at the Day Hospital of Yaounde Central Hospital between January and March 2024. The analytical dataset included 460 adults living with HIV receiving ART. Prevalent hypertension was coded as a binary outcome. Robust Poisson regression was used to estimate prevalence ratios (PRs) and adjusted prevalence ratios (aPRs) because hypertension was common. Sensitivity models were fitted to clarify the interpretation of cumulative ART duration in relation to current age. Among 460 participants, 199 (43.3

Single nucleotide polymorphisms (SNPs) are genetic risk factors for type 2 diabetes (T2D). SNPs of the cryptochrome circadian regulator 2 (CRY2), hepatocyte nuclear factor 1α, prospero homeobox 1 and glucose-6-phosphatase catalytic subunit (G6PC2) genes are associated with T2D. To the best of our knowledge, however, the association is unclear in African patients and the burden of T2D is growing rapidly in Africa. The present study aimed to investigate SNPs of cryptochrome circadian regulator 2 (CRY2), hepatocyte nuclear factor 1α, prospero homeobox 1 and glucose-6-phosphatase catalytic subunit (G6PC2) genes in T2D in a South African population. The study included 310 participants with T2D and 310 healthy controls. Demographic and lifestyle characteristics were self-reported, while anthropometric and biochemical measurements were determined using standard methods. Plasma glucose and insulin were measured by enzymatic hexokinase method and paramagnetic particle chemiluminescence assay, respectively. Highly sensitive c-reactive protein (hs-CRP) was measured by ELISA. iPLEX SNP genotyping was used for SNP analysis and results were confirmed by Sanger sequencing. Insulin resistance measured using the homeostasis model assessment of insulin resistance (HOMA-IR) formula was significantly higher in carriers of the recessive rs11605924 (P=0.049), fasting plasma glucose was significantly lower in carriers of the recessive rs560887 (P=0.015) and highly sensitive c-reactive protein levels were significantly lower in carriers of the recessive rs1169288 (P=0.018). The risk of T2D was significantly higher in participants with the recessive rs560887 [odds ratio (OR)=1.58, 95% CI, 1.02-2.44, P=0.041) and rs11605924 (OR=1.82, 95% CI, 1.03-3.23, P=0.041) compared with the dominant alleles. CRY2 and G6PC2 SNPs were associated with an increased risk of T2D and may partly contribute to high prevalence of T2D in the mixed ancestry South African population. Further studies are warranted to validate these findings in other African populations and explore downstream pathways.

Background and Objectives: Several micro- and macro-nutrient malnutrition states that are routinely assessed during clinical care of women in the antenatal period have been proposed as risk factors for preeclampsia. However, there is a paucity of data on the potential use of these biomarkers for detection of preeclampsia. The aim of this case-control study was to investigate the association of biomarkers from routine clinical tests, and those specific to micro- and macro-nutrient malnutrition, with the risk of preeclampsia. Materials and Methods: Venous blood samples of 250 participants with preeclampsia and 150 pregnant women without preeclampsia were collected and assayed immediately for the full blood count, urea and electrolytes, high-density cholesterol (HDL), total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL), oxidized low-density lipoprotein cholesterol (OxLDL), and selenium, in addition to urine iodine concentration (UIC). Results: The serum potassium/magnesium ratio (K+/Mg2+), UIC, fasting plasma glucose (FPG), thyroid stimulating hormone (TSH), lymphocyte percentage (L/WBC%), and the oxidized LDL/albumin ratio (OxLDL/Alb) were identified as independent predictors of preeclampsia. Conclusions: Serum potassium/magnesium ratio and other analytes essential for various biological processes, some of which are assayed during routine care, were significantly associated with preeclampsia, warranting further exploration as potential screening biomarkers in low-resource settings.

South African women experience high rates of abuse and cardiometabolic diseases, but research on their relationship is less investigated. This study examined the associations of exposure to abuse in childhood and adulthood with cardiometabolic risk factors [body mass index (BMI), waist circumference (WC), systolic (SBP) and diastolic blood pressure (DBP), total cholesterol (TC), HbA1c] over three years among women aged 18–40 years. The longitudinal Rape Impact Cohort Evaluation (RICE) study, conducted between 2014 and 2019, examined the associations of self-reported exposures to childhood abuse (CA) (any, sexual, physical, emotional CA and parental neglect < 18 years of age), lifetime intimate partner violence (IPV) (any, sexual, physical, emotional and economic IPV) and lifetime non-partner rape with cardiometabolic outcomes. These were explored using linear mixed-effects models, with the inclusion of the interaction terms, (1) ‘abuse/trauma*rape-exposed’; (2) ‘abuse/trauma*baseline-rape exposure*time’ to account for potential effects of baseline rape-exposure or time. Cardiometabolic data were collected at baseline (N = 1617; mean age 25.3 years), 12 (N = 1178), 24 (N = 925) and 36 months (N = 571). Exposures to any CA (β = 0.79; se = 0.27; p = 0.003), physical CA (β = 0.68; se = 0.27; p = 0.013) and greater frequency of physical CA (β = 0.73; se = 0.36; p = 0.042) were associated with rising BMI over 3 years of follow-up. There was no evidence of significant effects between baseline-rape exposure or time and most CA types in the associations examined (p > 0.05 for all interaction tests). An exception was found for sexual CA, where baseline-rape exposure influenced its association with WC (p = 0.010 for the interaction test). Time also affected the associations of emotional CA with both WC and BMI (ps ≤ 0.039 for the interaction tests). Exposures to IPV or lifetime non-partner rape were not significantly associated with increased changes in any cardiometabolic variables investigated, and no effects of baseline rape-exposure or time. This prospective analysis demonstrated that childhood abuse experiences were associated with increased BMI levels over 3 years of follow-up in young South African women. Further research over a longer period is required to clearly delineate the effect of abuse exposure on cardiometabolic diseases.

AIM:South Africa has a high burden of non-communicable diseases (NCDs) and experienced a high COVID-19 caseload, while the healthcare system was already overstretched. The aim of this study was to examine the perceptions and experiences of 1) healthcare professionals (HPs) of COVID-19 and NCD management, and the preparedness of health systems to provide NCD care, and 2) people living with NCDs (PLWNCDs) on the care they received, their mental health status and the availability of health information during the COVID-19 pandemic in South Africa. METHODS:We recruited a convenience sample of 1) HPs who worked in healthcare management, i.e., public health officials and healthcare workers who provided care and engaged with patients in any healthcare capacity, and 2) PLWNCDs with ≥1 NCD. Questionnaires comprised quantitative and some open-ended follow-up questions. SPSS was used to analyse the quantitative data, and content analysis with inductive reasoning was used to evaluate the open-ended questions. RESULTS:This cross-sectional study comprised 31 HPs and 79 PLWNCDs. The provision of COVID-19 care was perceived to be adequate by HPs while NCD care was poor with disruptions of services, including for emergency and specialised NCDs care. Strategies to care for non-COVID-19 illnesses during the pandemic were lacking. This would have serious long-term consequences for PLWNCDs and the healthcare system. Perceptions of inadequate NCD care were repeated by PLWNCDs; 49% felt they received 'very little' or no adequate care and 18% had a scheduled appointment cancelled. Further, many PLWNCDs (52%) felt anxious, lonely or frightened during the pandemic and 15% felt their mental health had deteriorated, but only a small proportion sought medical attention. The utility of digital health was positively perceived by both HPs and PLWNCDs and could contribute to better health provision during crises. CONCLUSIONS:Policies are needed to ensure that NCD care will not be neglected during future crises and to encourage PLWNCDs to access healthcare services timeously during such periods. Potential strategies may utilise digital health apps to improve care and to address the mental healthcare needs of PLWNCDs.

Importance: Multimorbidity, the coexistence of multiple long-term conditions, is a growing public health challenge in South Africa. Understanding the patterns of multimorbidity and their socioeconomic determinants is crucial for developing prevention and control solutions. Objective: To identify and characterize multimorbidity clusters and their socioeconomic determinants in the South African population using data from the Demographic and Health Survey (DHS). Design, Setting, and Participants: This cross-sectional study used data from the recent South Africa DHS, a nationally representative household survey. The study included 5,342 individuals aged 18 years and above who participated in the adult health module of the survey. Data were collected through interviews and biomarker measurements between June and November 2016. Main Outcome and Measures: The primary outcome was multimorbidity, defined as the presence of two or more chronic conditions. Twelve chronic conditions were considered: tuberculosis, hypertension, stroke, high blood cholesterol, anaemia, chronic bronchitis, diabetes, asthma, cancer, heart disease, HIV, and chronic pain. Socioeconomic determinants included wealth index, education level, occupation, health insurance, marital status, age, sex, ethnicity, and media access. Results: Of the 5,342 participants, 2,382 (44.6%) had multimorbidity. Four distinct multimorbidity clusters were identified: "Low Morbidity Group" (low prevalence of chronic conditions), "Cardiometabolic Cluster" (high prevalence of hypertension and diabetes), "Chronic Infectious Disease Cluster" (high prevalence of tuberculosis and HIV), and "Complex Chronic Disease Cluster" (high prevalence of multiple chronic conditions, including cancer, stroke, and heart attack). Multinomial logistic regression analysis revealed socioeconomic disparities in multimorbidity patterns, with lower levels of education, unemployment, and poverty associated with membership in the clusters characterized by a higher burden of chronic diseases. Conclusions and Relevance: This study identified four distinct multimorbidity clusters in the South African population, each characterized by unique patterns of chronic disease co-occurrence and socioeconomic determinants. The findings highlight the need for tailored interventions and policies that address the specific needs of each multimorbidity cluster while also tackling the underlying social and economic determinants of health. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study did not receive any funding ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethical approval for the SADHS was obtained from the South African Medical Research Council's Ethics Committee. Informed consent was obtained from all participants before data collection. This study used de-identified data from the SADHS and adhered to the ethical guidelines for secondary data analysis. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present work are contained in the manuscript

CONTEXT:Sex hormone-binding globulin (SHBG) and testosterone are differentially associated with type 2 diabetes (T2D) risk. OBJECTIVE:This work aimed to investigate whether the associations between SHBG, testosterone, and T2D risk differ by HIV and menopausal status in Black African women living with HIV (WH) and without HIV (WOH). METHODS:This cross-sectional observational study took place at the Health Research Unit in Soweto, Johannesburg, South Africa. A total of 81 premenopausal (57 WOH, 24 WH) and 280 postmenopausal (236 WOH, 44 WH) women from the Middle-Aged Soweto Cohort (MASC) participated. Main outcome measures included circulating SHBG and sex hormones, body composition (dual-energy x-ray absorptiometry), insulin sensitivity (Matsuda index), secretion (insulinogenic index) and clearance, and β-cell function (disposition index, DI). Dysglycemia was defined as either impaired fasting or postprandial glucose or T2D. RESULTS:SHBG was higher and total and free testosterone were lower in postmenopausal WH than WOH (all P ≤ .023). Irrespective of HIV serostatus, SHBG was positively associated with Matsuda index, insulin clearance, and DI and inversely with HOMA-IR (all P < .011). The association between SHBG and Matsuda index was stronger in premenopausal than postmenopausal women (P = .043 for interaction). Free testosterone (and not total testosterone) was only negatively associated with basal insulin clearance (P = .021) and positively associated with HOMA-IR (homeostatic model assessment of insulin resistance) in premenopausal and not postmenopausal women (P = .015 for interaction). CONCLUSION:We show for the first time that midlife African WH have higher SHBG and lower total and free testosterone than WOH, which corresponded to their higher β-cell function, suggesting a putative protective effect of SHBG on T2D risk in WH.

Aim: To describe the distribution of childhood obesity and their related comorbidities in <12-year-old children assessed at a South African tertiary hospital from 2012 to 2022. Methods: In this retrospective electronic chart review, data extracted comprised socio-demographic and lifestyle histories, physical examination and biochemical analyses. World Health Organisation child growth reference defined obesity as z-score ≥2 standard deviations (SD) for 5-19-year-olds, and z-score ≥3 SD for <5-year-olds. Systolic blood pressure and/or diastolic blood pressure ≥95th percentile and 90–94th percentile for age, gender and height, defined hypertension and prehypertension, respectively. Type 2 diabetes and prediabetes diagnoses were based on oral glucose tolerance tests or random blood glucose levels. Dyslipidaemia was deemed present with any abnormality of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglycerides. Results: Among 430 participants, 52.1 % (n = 224) male, 27.9 % (n = 120) ≤5-years-old and 64.7 % black African, unhealthy lifestyle behaviours were prevalent: 42.3 % spent <30 min/day on physical activity, 43.5 % spent >2 h/day on screen time and 47.9 % consumed soft drinks daily. Family history of obesity (41.9 %), diabetes (40.5 %) and hypertension (40.0 %) was common. Among participants, hypertension (46.1 %) and prehypertension (12.8 %) were high. Type 2 diabetes was low at 1.6 % but prediabetes was 3.3 %. Any dyslipidaemia was prevalent at 30.2 %. Conclusions: The high burden of cardiometabolic comorbidities in children with obesity warrants concerted interventions at young ages to prevent worsening of comorbidities and the reversal of prehypertension and prediabetes. Unhealthy dietary habits, low activity levels and sedentary behaviours in children need to be urgently targeted to reduce obesity and its comorbidities.

Introduction:Sickle cell disease (SCD) is most prevalent in Sub-Saharan Africa (SSA), where incomplete patient profiles and limited management strategies hinder research and healthcare standards. Methods:We describe the first large-scale and multinational assessment of 13,403 SCD patients enrolled from 2017-2021 across 31 facilities in Ghana, Nigeria, and Tanzania into the SickleInAfrica consortium registry. We used hierarchical regression models to estimate and analyze the demographics, adoption levels of SCD diagnosis and therapies. Results:The average age at diagnosis was 3 months, 19 months and 3 years in Ghana, Nigeria and Tanzania respectively, reflecting differences in country-specific newborn screening programs and policies. Hydroxyurea (HU) use was highest in Ghana (21%), followed by Nigeria (12%) and Tanzania (6%), with significant variability across facilities. Sex differences in SCD management were observed, with males more likely to receive HU and blood transfusions. At the consortium level, HU initiation correlated with enrolment age rather than age at diagnosis, highlighting the need for earlier intervention. Conclusions:Our findings highlight the potential of the SickleInAfrica registry toward enhancing understanding of regional disparities in SCD care and potential gender inequalities, emphasizing the need for enabling policies toward strengthened SCD research and improved quality of life and care of patients in Africa.