African Ethnicity Research Articles

Proteome profiling in patients with peripartum cardiomyopathy according to ethnicity a biomarker study on the EORP cohort

Abstract Background Peripartum cardiomyopathy (PPCM) is a pregnancy-associated form of heart failure, which occurs in previously healthy women towards the end of pregnancy and in the first months postpartum. Previous reports showed a varying prevalence of PPCM across different regions and potentially a higher incidence in patients with black African ethnicity. The correct and timely diagnosis remains challenging and there is a need for novel disease-specific biomarkers. Accuracy in diagnosing PPCM can be improved by using serum-protein biomarkers such as QSOX1, adiponectin and ITIH3 in addition to NT-proBNP. However, it still needs to be ascertained whether there are ethnic differences in proteomic profiles amongst patients with PPCM with different ethnicities. Aims To delineate possible differences in serum protein biomarker profiles across different ethnic groups within the EURObservation Research Programme (EORP) multi-national cohort of women with PPCM. Methods Demographic and clinical data, as well as serum samples were collected from 84 patients with PPCM from seven EORP participating countries. Serum proteomic profiling was conducted using DIA-based label-free quantitative (LFQ) LC-MS at the time of diagnosis from depleted serum samples. Mass spectrometry data were analyzed by Spectronaut v15 using a study-specific spectral library. From the 84 patients in the EORP PPCM registry on whom we performed proteomic analyses, 82 patients self-declared their ethnicity. These 82 patients were assessed for any ethnical differences in their proteomic expression profile using unsupervised principal component analysis (PCA). Results In this cohort of 82 women with PPCM, the mean age was 30.5±6.7 years (Table 1). Three quarters of this cohort had no hypertension during pregnancy and only 13.8% had a prior diagnosis of PPCM. The mean left ventricular ejection fraction (LVEF) was 35% at time of first diagnosis, with no difference between the ethnic groups. However, women of Middle Eastern decent had more severe LV dilatation (LVEDD: 64.0 (62.0-65.0) mm). Three hundred and twenty-nine (329) proteins were identified in the serum samples. As depicted in Figure 1, PCA did not yield a distinct separation between the different ethnic groups. Principal component 1 (PC1) accounted for 15.2% of the total variability in protein expression among ethnic groups, PC2 explained a comparatively lower percentage at 12%. Conclusion The protein biomarkers identified in PPCM patients showed no discernible racial differences, demonstrating consistent performance across all ethnic groups.

Asthma symptoms, severity, and control with and without a clinical diagnosis of asthma in early adolescence in sub-Saharan Africa: a multi-country, school-based, cross-sectional study.

Rapid urbanisation and population growth in sub-Saharan Africa has increased the incidence of asthma in children and adolescents. One major barrier to achieving good asthma control in these adolescents is obtaining a clinical diagnosis. To date, there are scant data on prevalence and severity of asthma in undiagnosed yet symptomatic adolescents. We therefore aimed to assess symptom prevalence and severity, the effect of symptoms on daily life, and objective evidence of asthma in young adolescents from sub-Saharan Africa with and without a clinical diagnosis of asthma by spirometry and fractional exhaled nitric oxide (FeNO). We designed a two-phase, multi-country, school-based, cross-sectional study to assess symptom prevalence and severity in sub-Saharan African adolescents. In phase 1 we surveyed young adolescents aged 12-14 years who were attending selected primary and secondary schools in Blantyre in Malawi, Durban in South Africa, Harare in Zimbabwe, Kampala in Uganda, Kumasi in Ghana, and Lagos in Nigeria. The adolescents were screened for asthma symptoms using the International Study of Asthma and Allergies in Children (ISAAC) questionnaire. Then, after opt-in consent, symptomatic adolescents were invited to complete a detailed survey on asthma severity, treatment, and exposure to environmental risk factors for phase 2. Adolescents performed the European Respiratory Society's diagnostic tests for childhood asthma. A positive asthma test was classified as a forced expiratory volume in 1 sec (FEV1) predicted under 80%, a FEV1 under the lower limits of normal, or FEV1 divided by forced vital capacity (FEV1/FVC) under the lower limits of normal; positive bronchodilator responsiveness or reversibility was defined as either an increase in absolute FEV1 of 12% or more, or an increase of 200 mL or more, or both, after 400 μg of salbutamol (shortacting β2 agonist) administered via a metered-dose inhaler and spacer, or FeNO of 25 parts per billion or higher, or any combination of these. The study was registered with ClinicalTrials.gov (NCT03990402) and is complete. Between Nov 1, 2018, and Nov 1, 2021, we recruited 149 schools from six regions in six sub-Saharan countries to participate in the study. We administered phase 1 asthma questionnaires from Jan 20, 2019 to Nov 11, 2021, and from 27 407 adolescents who were screened, we obtained data for 27 272 (99·5%). Overall, 14 918 (54·7%) adolescents were female and 12 354 (45·3%) adolescents were male, and the mean age was 13 years (IQR 12-13); nearly all recruited adolescents were of black African ethnicity (26 821 [98·3%] of 27 272). In phase 1, a total of 3236 (11·9% [95% CI 11·5-12·3]) reported wheeze in the past 12 months, and 644 (19·9%) of 3236 had a formal clinical diagnosis of asthma. The prevalence of adolescents with asthma symptoms ranged from 23·8% in Durban, South Africa to 4·2% Blantyre, Malawi. Using ISAAC criteria, severe asthma symptoms were reported by 2146 (66·3%) of 3236 adolescents, the majority of whom (1672 [77·9%] of 2146) had no diagnosis of asthma by a clinician. Between July 16, 2019, and Nov 26, 2021, we administered the phase 2 questionnaire to the 1654 adolescents who had asthma symptoms in phase 1 and consented to proceed to the second phase. In the phase 2 cohort, 959 (58·0%) were female and 695 (42·0%) were male, and the mean age was 13 years (IQR 12-14). One or more diagnostic tests for asthma were obtained in 1546 (93·5%) of 1654 participants. One or more positive asthma tests were found in 374 (48·8%) of 767 undiagnosed adolescents with severe symptoms, and 176 (42·4%) of 415 of undiagnosed adolescents with mild-to-moderate symptoms. Of the 392 adolescents in phase 2 with clinician-diagnosed asthma, 294 (75·0%) reported severe asthma symptoms, with 94 (32·0%) of those with severe symptoms not using any asthma medication. In general, findings in both phases 1 and 2 were consistent across sub-Saharan African countries. A large proportion of adolescents in sub-Saharan Africa with symptoms of severe asthma do not have a formal diagnosis of asthma and are therefore not receiving appropriate asthma therapy. To improve the poor state of asthma control in sub-Saharan Africa, potential solutions such as educational programmes, better diagnosis, and treatment and screening in schools should be considered. UK National Institute for Health and Care Research and UK Medical Research Council.

Anticoagulant therapy in pregnant women with mechanical and bioprosthetic heart valves.

The aim of the present study was to review maternal and fetal outcomes in pregnant women with prosthetic heart valves. A retrospective record review of pregnant women with prosthetic heart valves on anticoagulation was performed at the Specialist Cardiac Antenatal Clinic, Johannesburg South Africa from 2015 to 2023. Fifty pregnancies with mechanical heart valves and three with tissue valves, on anticoagulation for comorbid atrial fibrillation were identified. The majority were of African ethnicity at a mean age of 33 ± 6 years. Anti-Xa adjusted enoxaparin was commenced at 10.5 ± 5.6 weeks' gestation until delivery in 48 (90.6%) pregnancies and warfarin was continued in five (9.4%) pregnancies. The live birth rates on enoxaparin and warfarin were 56.3% (95% confidence interval [CI]: 42.3-69.3) and 20.0% (95% CI: 2.0-64.0), respectively. There were 12 (22.6%) miscarriages at a mean of 11.3 ± 3.7 weeks' gestation, four (7.5%) intrauterine fetal deaths on warfarin and two (3.8%) warfarin embryopathy/fetopathy. The rates of antepartum/secondary postpartum bleeding and primary postpartum bleeding were 29.4% (95% CI: 18.6-43.1) and 5.9% (95% CI: 1.4-16.9), respectively. Maternal complications included anemia (n = 11, 20.8%), arrhythmia (n = 2, 3.8%), heart failure (n = 2, 3.8%) and paravalvular leak (n = 2, 3.8%). There was one (1.9%) mitral valve thrombosis and one (1.9%) stuck valve in pregnancies who defaulted warfarin prior to pregnancy. There were no maternal deaths. Multidisciplinary management of pregnant women with prosthetic heart valves with anti-Xa adjusted low molecular weight heparin throughout pregnancy represents an effective anticoagulation option for low-middle-income countries.

Language and Group-based Power: Myths, Proverbs and Metaphors as Depositories of Gendered and Ethnic Identities in Perpetua Nkamanyang Lola’s Revised Edition of "The Lock on my Lips (2023)"

Gender and Ethnicity are two types of group distinctions with which group-based power is associated and, in most postcolonial African urban contexts, gender and ethnicity intersect to shape our identities, opportunities and the challenges we face. Drawing from postcolonial, queer and feminist theories, this study examines the role of language in the construction of group-based power structures. The study examines the gender and ethnic specific function of Language (specifically myths, proverbs, metaphors, idioms and witty sayings) in the revised edition of Lola’s The Lock On My Lips with the view of demonstrating that the budding dramatist employs these linguistic devices to invest her work with a truly African sensibility and flavour, but mainly to show the role language plays in the social construction of gender and ethnic otherness.

A cross-sectional study of the spectrum, aetiology and clinical characteristics of adult mitral valve disease at Chris Hani Baragwanath Academic Hospital.

Valvular heart disease constitutes a considerable amount of cardiovascular morbidity and mortality worldwide. There is a scarcity of data from Africa. In this descriptive, cross-sectional study, we documented the demographic, clinical and echocardiographic features of current patients with adult mitral valve disease (MVD) at Chris Hani Baragwanath Academic Hospital from December 2018 to March 2019. The study included 134 patients (mean age 50 ± 13.3 years) and 77% were female. The majority were of African ethnicity (96%). Mitral regurgitation (39%), followed by mixed MVD (38%) were the dominant lesions. Mitral stenosis was found in 23% of the patients. The main aetiologies were rheumatic heart disease (80%), mitral valve prolapse (11%), myxomatous degeneration (6%) and infective endocarditis (3%). Hypertension (30%) and HIV (12%) were the main co-morbidities. Heart failure was present in 78% of the patients at index hospitalisation. The main complications were pulmonary hypertension (28%) and atrial fibrillation (14%). The patients with MVD tended to be older African females with co-morbidities who had predominant rheumatic mitral regurgitation.

Proteomic Analysis Identifies Dysregulated Proteins in Albuminuria: A South African Pilot Study.

Albuminuria may precede decreases in the glomerular filtration rate (GFR) and both tests are insensitive predictors of early stages of kidney disease. Our aim was to characterise the urinary proteome in black African individuals with albuminuria and well-preserved GFR from South Africa. This case-controlled study compared the urinary proteomes of 52 normoalbuminuric (urine albumin: creatinine ratio (uACR) < 3 mg/mmol) and 56 albuminuric (uACR ≥ 3 mg/mmol) adults of black African ethnicity. Urine proteins were precipitated, reduced, alkylated, digested, and analysed using an Evosep One LC (Evosep Biosystems, Odense, Denmark) coupled to a Sciex 5600 Triple-TOF (Sciex, Framingham, MA, USA) in data-independent acquisition mode. The data were searched on SpectronautTM 15. Differentially abundant proteins (DAPs) were filtered to include those with a ≥2.25-fold change and a false discovery rate ≤ 1%. Receiver-operating characteristic curves were used to assess the discriminating abilities of proteins of interest. Pathway analysis was performed using Enrichr software. As expected, the albuminuric group had higher uACR (7.9 vs. 0.55 mg/mmol, p < 0.001). The median eGFR (mL/min/1.73 m2) showed no difference between the groups (111 vs. 114, p = 0.707). We identified 80 DAPs in the albuminuria group compared to the normoalbuminuria group, of which 59 proteins were increased while 21 proteins were decreased in abundance. We found 12 urinary proteins with an AUC > 0.8 and a p < 0.001 in the multivariate analysis. Furthermore, an 80-protein model was developed that showed a high AUC ˃ 0.907 and a predictive accuracy of 91.3% between the two groups. Pathway analysis found that the DAPs were involved in insulin growth factor (IGF) functions, innate immunity, platelet degranulation, and extracellular matrix organization. In albuminuric individuals with a well-preserved eGFR, pathways involved in preventing the release and uptake of IGF by insulin growth factor binding protein were significantly enriched. These proteins are indicative of a homeostatic imbalance in a variety of cellular processes underlying renal dysfunction and are implicated in chronic kidney disease.

Metabolic Complications Associated with Use of Integrase Strand Transfer Inhibitors (InSTI) for the Treatment of HIV-1 Infection: Focus on Weight Changes, Lipids, Glucose and Bone Metabolism.

This review aims to summarize recently published peer reviewed papers on the influence of treatment with Integrase Strand Transfer Inhibitors (InSTI) in people with HIV (HIV) on metabolic health, including weight gain, lipid parameters, glucose homeostasis, and bone health. InSTI have a mild/moderate effect on weight gain in both antiretroviral (ART) naïve and ART experienced PWH, which is more pronounced in certain groups (i.e. women, people of Black African ethnicity, those with lower socioeconomic status, and older people). The effect on weight is also driven by other components of the ART regimen as well as previous exposure to certain ART. InSTI have a relatively safe profile in terms of lipid parameters and bone health, compared to other ART classes, although some studies suggest a greater risk of insulin resistance and diabetes in PWH using InSTI, especially 2nd generation InSTI. While there is some evidence suggesting a negative impact of InSTI on some aspects of metabolic health (weight gain and glucose homeostasis), they remain the preferred treatment option for most PWH, due to their high efficacy and tolerability. However, an individualised approach to ART choice in PWH should be used in order to avoid negative outcomes in populations at higher risks of metabolic complications.

Vessel density, macula thickness and foveal avascular zone measurements in young African adults with moderate myopia: A pilot study.

The aim of this study was to investigate the association between macula thickness and vessel density in African myopic and emmetropic eyes through the use of Spectral Domain Optical Coherence Tomography (OCT). The study population comprised African adults aged 18-35 years old. The study was conducted at a University eye clinic located in Durban, South Africa. Purposive sampling was utilised to obtain 59 participants of whom 24 were myopes and 35 were emmetropes. Vessel density (VD), foveal avascular zone (FAZ) and retinal thickness (RT) were obtained using the Heidelberg Spectralis OCT with angiography. Thereafter, a multivariate linear regression was used to investigate associations between the spherical equivalent myopic refractive error and VD, FAZ and RT for the myopic group only. Myopic participants had a mean spherical equivalent (MSE) and standard deviation (SD) of -4.79 D (1.27) while the emmetropic group had an MSE (SD) of -0.32 D (0.46). Both superficial and deep VD were significantly decreased at the central fovea (radius (r) = 0.4 mm), peri-foveal (r = 1.10-1.45 mm) and para-foveal (r = 0.75-1.10 mm) sectors in myopes when compared with emmetropes. Myopes showed a significant reduction in RT in the inner retinal layer across the inferior and temporal zones of the peri-foveal region as well as the inferior and temporal zones of the para-foveal region when compared with emmetropes. A significantly smaller FAZ was found at both the superficial and deep vascular plexuses (p < 0.001). In African myopes, significant associations were not found between MSE and VD or FAZ and macula retinal thickness. Retinal vascular and thickness reduction may occur in young African adults with moderate myopia. A broad-based study targeting VD and IRT in African myopes is proposed to confirm preclinical myopic macula disruptions in adults of African ethnicity. OCT angiography should be considered when monitoring progressive myopia.

The Glass Ceiling in Global Health: Perspectives of Female and Male Anesthesiologists.

Gender equity is essential for improving health outcomes globally. Despite comprising 75% of the global health workforce and dominating academic global health programs, women remain underrepresented in leadership positions in global health organizations. Our study aimed to identify potential gender differences in the beliefs and attitudes regarding barriers that women anesthesiologists encounter in pursuing careers and leadership roles in global health and to identify recommendations for improving gender equity in global health. We conducted a cross-sectional online survey focusing on career leadership opportunities and challenges uniquely faced by women clinicians in global health. We obtained permission from the World Federation of Societies of Anaesthesiologists to distribute our questionnaire to their leadership committee members during 2 months (May-July 2022). The questionnaire was distributed to 164 study participants with 67 individuals (44.8% female) based in 38 different countries completing the survey (response rate 40.9%). Overall, 47.8% of the participants aspired to a leadership position in global health and 58.2% agreed women face unique barriers to global health leadership (70.0% of women compared to 48.6% of men; P = .081). Female gender (odds ratio [OR], 19.22, P = .004) and divorced marital status (OR, 746.26, P = .004) were positively associated and African ethnicity (OR, 0.002, P = .017) was negatively associated with the perception of gender bias in their career growth. The main challenges included balancing work and family responsibilities, lack of female mentors or role models, gender-based discrimination, and limited opportunities for career advancement. Men acknowledged these challenges but reported personally experiencing them to a lesser extent, particularly concerning lack of opportunities (P = .005), inadequate pay (P = .000), and lack of training (P = .000). Gender disparities exist in the pursuit of global health careers. This study underscored that more women than men perceive barriers in pursuing leadership roles in global health and that men generally encounter these obstacles to a lesser extent. Female representation in leadership positions could be supported through evidence-informed policies that promote work-life balance, improve mentorship, offer equal opportunities for career advancement and adequate pay, and combat gender-based discrimination.

Investigation of Delayed Transfusion Reactions in Sickle Cell Disease Patients Polytransfused in the Brazilian Amazon.

Sickle cell disease (SCD) affects approximately 100,000 people in the United States and millions worldwide, with the highest prevalence of 70% of SCD being found in individuals of African ethnicity. Delayed hemolytic, alloimmunization, and anamnestic transfusion reactions in multiple transfusion patients need to be investigated and managed to avoid a worsening of the patient's clinical status. This paper aims to investigate delayed transfusion reactions in SCD patients who were polytransfused in the Brazilian Amazon. The clinical and laboratory indicators of SCD patients with more than four transfusions were investigated. The patients were treated at the Fundação Hospitalar de Hematologia e Hemoterapia do Estado do Amazonas, Brazil. A total of 44 polytransfused patients with SCD were followed. Regarding Rh phenotype, it was possible to observe a frequency of 26.6% (12) patients with the RZRZ (DCE/DCE) phenotype, in addition to 4.5% (two) patients with RH and RHCE variants. It was also possible to observe 20.5% (nine) patients with an alloimmunization reaction, who presented the following alloantibodies: anti-RhD, anti-E, anti-K, anti-Jkb, anti-N, anti-S, and anti-Dia, two of which are unidentified. Of these, four (44.4%) patients also presented autoantibodies, anti-e, and three unidentified antibodies, and four (44.4%) patients presented an anamnestic reaction, with anti-RhD, K, and Jkb antibodies. Of the 44 patients monitored, 54.4% (24) had clinical and laboratory indicators of a delayed hemolytic reaction. Delayed transfusion reactions, often neglected, occur frequently. Therefore, transfusions need to be monitored for at least 28 days, with medical investigation of clinical and laboratory indicators to make greater use of this therapeutic resource.

Long-term outcomes of childhood-onset systemic lupus erythematosus.

Data on the long-term outcome of patients with childhood-onset Systemic Lupus Erythematosus (cSLE) are scarce. Aims of this study were to describe the long-term outcomes of cSLE and to identify factors associated with the development of damage and persistent disease activity. We conducted a retrospective multicentre study using data from the PEDIALUP registry of the Juvenile Inflammatory Rheumatism (JIR) cohort database. Demographic characteristics, clinical manifestations, laboratory, radiological, histological and treatment data were collected from medical records during follow-up. A total of 138 patients with cSLE, diagnosed between 1971 and 2015, were included. With a median follow-up of 15.4 [9.6-22.4] years, 51% of patients had a SLICC-Damage Index score ≥ 1 at last follow-up with the musculoskeletal, cutaneous, renal, neurological, and cardiovascular damage being the most common manifestations. The proportion of patients with a SLICC-DI score ≥ 1 increased significantly with the duration of the follow-up (p< 0.001). On multivariate analysis, duration of follow-up was associated with increased risk of cumulative damage (OR 1.08, 95% CI 1.01, 1.15, p= 0.035). At the last visit, 34% of patients still had active disease with a SLEDAI score of ≥ 6. On multivariate analysis, Sub-Saharan African ethnicity was associated with 7-fold increased odds of having active disease at the last visit compared with Caucasians (OR 7.44, 95% CI 2.24, 24.74, p= 0.0002). The prevalence of damage remains high in patients with cSLE even when the diagnosis of c-SLE has been made in the recent decades.

Dying well in Aotearoa New Zealand for ethnic minority communities: a time for reclamation?

Despite technological advances and a disproportionate increase in health expenditure at the end-of-life, most New Zealanders die in hospital or in aged residential care. This counters the aspirations espoused by Te Whatu Ora (Health New Zealand) for all New Zealanders "to live well, age well and die well in their homes and communities." Furthermore, despite reported inequities in end-of-life care experienced by ethnic minority communities (EMCs) overseas, and increasing proportions of people identifying with Asian, Middle Eastern, Latin American and African ethnicities in Aotearoa New Zealand, local data, research and policies addressing healthcare needs of EMCs at end-of-life are scant. Acknowledging this invisibility, we reflect on and discuss the current discourses on death and dying, the complex experiences at end-of-life for EMCs, including concepts of a "good death", the impact of recent existential crises (e.g., COVID-19 pandemic, climate change) on death awareness, and the global rise to reclaim dying as an important part of living. We argue for the need: a) to partner with ethnic communities to co-design culturally safe end-of-life health services, and b) to adopt a "compassionate communities" public health approach that can support people of EMCs at the end-of-life to die well.

Bilateral Aggressive Mooren Ulcer in the Setting of Bilateral Pterygia and Pregnancy: A Unique Case.

To report an unusual case of bilateral aggressive Mooren ulcer that occurred in the setting of bilateral pterygia and showed a relentless course during pregnancy. A 39-year-old woman of Black African ethnicity, 36-week pregnant, presented to the eye casualty with bilateral nasal corneal ulcer and associated melt around preexisting pterygia. A detailed workup including microbial evaluation, culture and sensitivity, polymerase chain reaction for herpes simplex virus, varicella zoster virus, and cytomegalovirus, inflammatory blood profile, autoimmune markers, and human leucocyte antigen (HLA) screening was undertaken. Treatment was initiated in a stepwise approach. Infections and systemic autoimmune and rheumatologic conditions were ruled out. A diagnosis of bilateral Mooren ulcer was made by exclusion. The peripheral blood was positive for HLA DQ2. As the condition seemed refractory to medical management (topical steroids and intravenous pulse methylprednisolone followed by oral prednisolone and topical cyclosporine), urgent bilateral conjunctival resection with multilayered amniotic membrane transplantation was performed to reduce the inflammatory stimulus and keratolysis. Stabilization of the condition warranted the need for systemic immunosuppressive agents. Using a multidisciplinary approach, in liaison with Obstetricians and Rheumatologists, the patient was planned for an earlier elective Cesarean section and commencement of oral mycophenolate mofetil postpartum, which aided in successful control of the disease. Mooren ulcer could follow an aggressive course during pregnancy, especially in the setting of preexisting pterygium. The complex hormonal and immunological changes during pregnancy and the delivery of inflammatory mediators directly onto the cornea by pterygium could contribute to the severity. A well-planned, stepwise, and multidisciplinary management is pivotal for the treatment of this condition.

Identifying Populations at Risk for Lung Cancer Mortality from the National Health and Nutrition Examination Survey (2001-2018) Using the 2021 USPSTF Screening Guidelines.

Lung cancer (LC) is the leading cause of cancer mortality in the United States. To combat this predicament, early screening and critically assessing its risk factors remain crucial. The aim of this study was to identify the value of specific factors from the National Health and Nutrition Examination Survey (NHANES) from 2001-2018, as they relate to lung cancer mortality in the US Preventive Services Task Force (USPSTF)-eligible population. A total of 3545 adults who met USPSTF criteria were extracted from 81,595 NHANES participants. The LC Death Risk Assessment Tool was used to calculate the number of deaths per 1000 individuals. The Mann-Whitney U test and one-way ANOVA determined the statistical significance of the factors involved in LC mortality. Male sex, African and Hispanic ethnicity, lower education attainment, and secondhand exposure to cigarette smoke correlated with an increased risk of LC mortality. Additionally, the factor of emotional support from NHANES data was analyzed and did not show any benefit to reducing risk. By identifying individuals at high-risk, preventative measures can be maximized to produce the best possible outcome.

Evaluation of Cisplatin-Induced Acute Kidney Injury in Patients Coprescribed Serotonin Receptor Antagonists: A Retrospective Analysis.

Cisplatin is an effective first line therapy for a variety of cancers. Cisplatin is highly emetogenic and resulting volume depletion can contribute to acute kidney injury (AKI). Anti-emetic drugs such as 5-hydroxytryptamine type 3 receptor antagonists (5-HT3RAs) are commonly prescribed to prevent this complication. Preclinical studies suggest first generation 5-HT3RAs may alter the renal clearance and increase cisplatin toxicity. This retrospective study evaluated whether different 5-HT3RAs modify the risk of AKI in patients receiving cisplatin. Patients with cancer who received cisplatin between January 1, 2010 and December 31, 2016 were included. Patients over 18 years old with available data for baseline and post-treatment serum creatinine, cisplatin cumulative dose, and administration of 5-HT3RAs including first generation (ondansetron, granisetron, and ramosetron) and second generation (palonosetron) were analyzed. AKI defined as 1.5x increase in serum creatinine. Fisher's exact and Wilcoxon rank-sum tests were used to assess univariable associations between baseline covariates and AKI, and logistic regression for multivariable associations with AKI. Of 8703 patients identified with cisplatin exposure, 6889 were included. A total of 3881 (56.3%) patients received at least one 5-HT3RA, including palonosetron (3750, 54.4%), ondansetron (1399, 20.3%) and granisetron (11, 0.2%). AKI developed in 1666 (24.2%) patients following cisplatin. Patients who received any 5-HT3RAs were less likely to experience AKI as compared to patients that did not (22.6% vs 26.2%, p=0.001). Older age, male gender, African ethnicity, and cumulative cisplatin dose were univariately associated with higher risk for AKI (P<0.001). After adjusting for these variables, use of any of these antiemetic drugs was protective for AKI (OR 0.84, 95% CI: 0.75, 0.94; P= 0.003) with no difference detected between type of 5-HT3RA. Nephrotoxicity continues to be a concern following cisplatin therapy. Given its emetogenic nature, use of antiemetic drugs such as 5-HT3RAs can lessen emesis and lower risk of kidney injury. This retrospective analysis supports use of any 5-HT3RAs to lower risk of AKI.

#2531 Autosomal dominant polycystic kidney disease with cerebrovascular complications in South Africa: clinical characteristics and prognosis

Abstract Background and Aims Autosomal dominant polycystic kidney disease (ADPKD) is the most prevalent inherited kidney disease worldwide. It is characterized by inexorable cyst formation in the kidney and extrarenal manifestations, such as liver cysts, colonic diverticula, valve prolapse, and cerebrovascular complications. The latter is associated with high morbidity and mortality and results from a higher prevalence of cerebral aneurysms (12–25%) compared to the general population. we aimed to evaluate the clinical and imaging characteristics and prognosis of patients with ADPKD with cerebrovascular complications. Method We reviewed the electronic medical records of patients seen at the nephrology department of the Inkosi Albert Luthuli Central Hospital from 2006 to 2023. We are reporting on 13 patients with ADPKD complicated by intracerebral haemorrhage (ICH), subarachnoid haemorrhage (SAH), non-traumatic subdural hematomas (NTSDH), and unruptured intracranial aneurysms (UIAs). We extracted demographic, clinical, and paraclinical data. We performed bivariate analysis to find associated factors. Results Of the 13 patients, 8 were women and 5 men with 6 of African ethnicity, 4 Asians, and 2 Caucasians. The median age at presentation was 52 (31, 72). Vascular risk factors included hypertension (mean SBP150.3 ± 17.25, mean DBP 84.5 ± 12.2), dyslipidaemia, and smoking. Most patients presented with various levels of altered consciousness. Imaging showed 4 NTSDH, 4 ICH, 3 SAH, and 2 unruptured aneurysms. The affected vessels were the left Middle Commutating Artery, the posterior perforating artery, and the anterior choroidal artery. Follow-up duration ranged from 1 to 15 years. The NTSDH reoccurred in 2 patients. Patients with unruptured aneurysms were managed conservatively while the others benefited from a surgery after which 2 died of surgical complications. These 2 patients who died were end-stage kidney disease(ESKD) and presented with a lower Glasgow Coma Scale. In Univariate analysis cerebrovascular haemorrhage was associated significantly with tobacco (P = 0.011), younger age at diagnosis of ADPKD (P = 0.010), and higher systolic BP (P = 0.021) but not ethnicity (P = 0.106). Conclusion Patients of African ethnicity were more likely to present with NTSDH and it reoccurred. Overall surgical management led to full recovery except for patients with ESKD and those with lower GCS.

History and the Problem of Dead Identity: Theorising the Revival of Zulu’s Extinct Culture in Zakes Mda’s the Zulus of New York

This article attempts to explore history as a medium of reviving South African extinct identity in Zakes Mda’s The Zulus of New York. The study theorises the impetus of rejuvenating such identity based on Mda’s description of the Zulu’s potential to perform their native socio-cultural traditions despite the colonial hegemony which limits their power to maintain their identity. It argues that this literary tendency is largely rooted in the peculiar theoretical discourse on South African subaltern and internally colonised identity vis-à-vis the West, namely the USA and Britain; a notion that tends to perpetuate Zulu’s native and pre-colonial vernacular discourses. Within this narrative, the Zulu’s nativism and the South African ethnicity are regarded as non-colonial powers since the indigenous tribes allegedly suffered under Western ruling nationalities in the annexed territories. Therefore, the study discovers the problematic implications of such an exclusive focus on the postcolonial perspective; and it questions the theoretical conception of subordination as an ‘internal colony’, which is decolonised by the Zulu. The study proposes arguments for the consideration of American and British domination as variant models of Western hegemony, and it emphasises the need for examining Zuluophone cultures when theorising Zulu postcolonial identity. It demonstrates how the Zulu minority may wage this metapolitical resistance using individual rights to challenge Western hegemony as an illiberal entity, and thus Zulu de-constitutes colonialism to restore indigenous demotic and territorial boundaries. Thus, indigenous Zulu people resist by seeking to constitutionally entrench their identity as the rightful ‘subject of justice.

Social determinants of health and long-term conditions in people of Black African and Black Caribbean ethnicity living with HIV in London: Aqualitative study.

People living with human immunodeficiency virus (HIV) are disproportionately impacted by socioeconomic deprivation and are at increased risk of developing other long-term conditions (LTCs). These illnesses require transformative action to tackle the adverse effects on their health. Data on lived experiences of LTCs among people living with HIV of Black African and Black Caribbean ethnicities are sparse, and how people with LTCs are impacted by social determinants of health (SDoH). Through a phenomenological study design this qualitative study, conducted in 2022, comprised four focus group discussions (FGDs) with 20 people of Black ethnicities living with HIV were purposively invited from a community organisation (CO) in London, including four semistructured interviews with CO staff. Following transcription, qualitative data were analysed thematically and measures to validate the findings were implemented. The findings are presented in terms of the following four levels of SDoH: (1) individual determinants (such as the impact of SDoH on lifestyle modification and self-management); (2) interpersonal determinants (such as positive experiences of accessing healthcare for LTCs); (3) clinical determinants (such as care pathway barriers)and (4) systemic determinants (such as systemic barriers related to race/ethnicity). It is necessary to provide ongoing and interactive education to community members who live with HIV, focusing on risks and management of LTCs. Additionally, individuals would benefit from support to navigate increasingly complex and fragmented health services. Health Service staff require cultural competence when caring for patients of Black African and Black Caribbean ethnicities with complex health and psychosocial needs. The research team collaborated with an HIVCOin South London from the very start of the project to agree the study design and learn about the realities of their daily lived experiences. Community collaborators helped to develop the semistructured interview and FGDtopic guides, and were directly involved in the data gathering, analysis and validation.

Impact of donor CYP3A5 genotype on pharmacokinetics of tacrolimus in South African paediatric liver transplant patients.

In the paediatric liver transplant programme in Johannesburg, South Africa (SA), tacrolimus is the calcineurin inhibitor of choice, comprising an essential component of the immunosuppression regimen. It is characterised by a narrow therapeutic index and wide interpatient variability, necessitating therapeutic drug monitoring of whole-blood concentrations. Pharmacogenetic research, although not representative of SA population groups, suggests that single-nucleotide polymorphisms within the cytochrome P450 3A5 (CYP3A5) gene contribute to the variability in tacrolimus dosing requirements. The rs776746 polymorphism, CYP3A5*3, results in a splice defect and a non-functional enzyme. Clinically, to reach the same tacrolimus concentration-to-dose ratio (CDR), expressors (CYP3A5*1/*1 and *1/*3) require a higher tacrolimus dose than non-expressors (*3/*3). To compare the pharmacokinetics of tacrolimus in paediatric liver transplant recipients with their donors' CYP3A5 genotypes, considering both donor and recipient characteristics. Blood samples from 46 living liver donors were collected, their genomic DNA was extracted, and their CYP3A5 genotype was established (polymerase chain reaction and restriction fragment length polymorphism analysis, validated by Sanger sequencing). The relationship of donor and recipient characteristics with the mean tacrolimus CDR was analysed using a general linear model. Non- confounding significant variables were included in a multiple regression model. The study showed that all expressor donors genotyped as CYP3A5*1/*1 were of black African self-reported race and ethnicity. During the first 15 days post-transplant, we found that children who received grafts from donor CYP3A5 expressors (CYP3A5*1/*1 and *1/*3) had significantly lower mean tacrolimus CDRs compared with those who received grafts from donor CYP3A5 non-expressors (*3/*3); the recipients of CYP3A5 expressor grafts therefore require higher doses of oral tacrolimus to achieve the same therapeutic target range. In addition, graft-to-recipient weight ratio and the CYP3A5 donor genotypes were independent factors that significantly (p<0.05) affected mean tacrolimus CDRs in recipients. In this study, we showed that all CYP3A5*1 homozygote donors were of black African self-reported race and ethnicity, and tacrolimus CDRs in paediatric living-donor liver transplant recipients were significantly affected by donor graft size and donor CYP3A5 genotypes. Information from this study may inform the development of an Afrocentric tacrolimus precision-medicine algorithm to optimise recipient safety and graft outcomes.

Case-control study of heart rate variability and sleep apnea in childhood sickle cell disease.

Obstructive sleep apnea (OSA) is common in sickle cell disease (SCD) despite the absence of overweight, suggesting a specific pathophysiology. We previously showed that otherwise healthy children with increased pharyngeal compliance, a main endotype of OSA, exhibited decreased sympathetic modulation. Our objective was to assess whether modifications of heart rate variability (HRV) and compliance are associated in SCD. Cases (children with SCD, African or Caribbean ethnicity) and controls (otherwise healthy children, same ethnicity), aged 4-18 years, were selected from our database of children referred for OSA and matched for sex, age, and obstructive apnea-hypopnoea index (OAHI) score. The children underwent polysomnography and acoustic pharyngometry (to compute compliance). HRV analyses were performed from 5 min ECG recordings in wakeful, NREM, and REM sleep states and from the whole night. Twenty-one pairs were analysed (median age 10.5 years, 24 girls). Children with SCD had lower BMI z-scores and more tonsil hypertrophy than control children. Children with SCD and OSA (OAHI ≥2/hour) were characterised by lower compliance than children with SCD without OSA. An inverse relationship between compliance and SD2 (HRV from whole night, inversely related to sympathetic modulation) was evidenced (negative relationship in SCD: R = -0.63, p = 0.002 vs. positive relationship in controls R = 0.59, p = 0.006). In conclusion, while the decrease in sympathetic modulation in control children may contribute to increasing pharyngeal compliance, its decrease seems protective in children with sickle cell disease, which underlines the specificity of OSAS pathophysiology in SCD that could be due to sickle cell disease related smooth muscle dystonia.