Profiling of warfarin pharmacokinetics-associated genetic variants: Black Africans portray unique genetic markers important for an African specific warfarin pharmacogenetics-dosing algorithm.

BACKGROUND: Warfarin dose variability observed in patients is attributed to variation in genes involved in the warfarin metabolic pathway. Genetic variation in CYP2C9 and VKORC1 has been the traditional focus in evaluating warfarin dose variability, with little focus on other genes. OBJECTIVE: We set out to evaluate 27 single nucleotide polymorphisms (SNPs) in the CYP2C cluster loci and 8 genes (VKORC1, ABCB1, CYP2C9, CYP2C19, CYP2C8, CYP1A2, CYP3A4, and CYP3A5) involved in pharmacokinetics of warfarin. PATIENTS/METHODS: 503 participants were recruited among black Africans and Mixed Ancestry population groups, from South Africa and Zimbabwe, and a blood sample taken for DNA. Clinical parameters were obtained from patient medical records, and these were correlated with genetic variation. RESULTS: Among black Africans, the SNPs CYP2C rs12777823G>A, CYP2C9 c.449G>A (*8), CYP2C9 c.1003C>T (*11) and CYP2C8 c.805A>T (*2) were significantly associated with warfarin maintenance dose. Conversely, CYP2C9 c.430C>T (*2), CYP2C8 c.792C>G (*4) and VKORC1 g.-1639G>A were significantly associated with maintenance dose among the Mixed Ancestry. The presence of CYP2C8*2 and CYP3A5*6 alleles was associated with increased mean warfarin maintenance dose, whereas CYP2C9*8 allele was associated with reduced warfarin maintenance dose. CONCLUSION: African populations present with a diversity of variants that are important in predicting pharmacogenetics-based warfarin dosing in addition to those reported in CYP2C9 and VKORC1. It is therefore important, to include African populations in pharmacogenomics studies to be able to identify all possible biomarkers that are potential predictors for drug response.

Generalist practitioners' self-rating and competence in electrocardiogram interpretation in South Africa.

BACKGROUND: Electrocardiogram (ECG) is the only practical, non-invasive method of recording and analysing cardiac abnormalities. It enables a primary healthcare (PHC) clinician to detect cardiac and non-cardiac abnormalities, some potentially life-threatening. Their early detection could save a patient's life. AIM: The aim of this study was to evaluate the competence of generalist practitioners in ECG interpretation. SETTING: This study was conducted at the Annual Refresher Course, Council for Scientific and Industrial Research (CSIR), Pretoria. METHODS: A cross-sectional study was conducted amongst 93 generalist practitioners, using a self-administered questionnaire containing 20 ECG tracings, commonly encountered in PHC. The tracings were categorised into primary ECG parameters, ECG emergencies and common ECG abnormalities. Competence was determined by the generalist practitioner's number of correctly interpreted ECG tracings. Data associations were computed using the Fisher's exact test. Statistical significance was set at p ≤ 0.05. RESULTS: Correct heart rate calculation was achieved by 14/83 (16.9%), ECG rhythm by 7/83 (8.4%), acute antero-septal myocardial infarction (MI) by 29/83 (34.9%), atrial fibrillation by 19/83 (22.9%) and cute inferior MI by 22/83 (26.5%) generalist practitioners. No correlation was found between the practitioners' number of years in practice and competence in ECG interpretation (p 0.05). The total number of correct answers achieved by all practitioners was 274/1860 (14.7%). CONCLUSION: The generalist practitioners had poor competency on ECG interpretation regardless of the number of years in practice. Their poor self-rating corresponded with the number of correct answers they provided. There is a need for continuous education in ECG interpretation.

Rationale and design of the comparison of 3 combination therapies in lowering blood pressure in black Africans (CREOLE study): 2 × 3 factorial randomized single-blind multicenter trial.

BACKGROUND: Current hypertension guidelines recommend the use of combination therapy as first-line treatment or early in the management of hypertensive patients. Although there are many possible combinations of blood pressure(BP)-lowering therapies, the best combination for the black population is still a subject of debate because no large randomized controlled trials have been conducted in this group to compare the efficacy of different combination therapies to address this issue. METHODS: The comparison of 3 combination therapies in lowering BP in the black Africans (CREOLE) study is a randomized single-blind trial that will compare the efficacy of amlodipine plus hydrochlorothiazide versus amlodipine plus perindopril and versus perindopril plus hydrochlorothiazide in blacks residing in sub-Saharan Africa (SSA). Seven hundred two patients aged 30-79 years with a sitting systolic BP of 140 mm Hg and above, and less than 160 mm Hg on antihypertensive monotherapy, or sitting systolic BP of 150 mm Hg and above, and less than 180 mm Hg on no treatment, will be centrally randomized into any of the 3 arms (234 into each arm). The CREOLE study is taking place in 10 sites in SSA, and the primary outcome measure is change in ambulatory systolic BP from baseline to 6 months. The first patient was randomized in June 2017, and the trial will be concluded by 2019. CONCLUSIONS: The CREOLE trial will provide unique information as to the most efficacious 2-drug combination in blacks residing in SSA and thereby inform the development of clinical guidelines for the treatment of hypertension in this subregion.

Seven key actions to eradicate rheumatic heart disease in Africa: the Addis Ababa communiqué.

Acute rheumatic fever (ARF) and rheumatic heart disease (RHD) remain major causes of heart failure, stroke and death among African women and children, despite being preventable and imminently treatable. From 21 to 22 February 2015, the Social Cluster of the Africa Union Commission (AUC) hosted a consultation with RHD experts convened by the Pan-African Society of Cardiology (PASCAR) in Addis Ababa, Ethiopia, to develop a 'roadmap' of key actions that need to be taken by governments to eliminate ARF and eradicate RHD in Africa. Seven priority areas for action were adopted: (1) create prospective disease registers at sentinel sites in affected countries to measure disease burden and track progress towards the reduction of mortality by 25% by the year 2025, (2) ensure an adequate supply of high-quality benzathine penicillin for the primary and secondary prevention of ARF/RHD, (3) improve access to reproductive health services for women with RHD and other non-communicable diseases (NCD), (4) decentralise technical expertise and technology for diagnosing and managing ARF and RHD (including ultrasound of the heart), (5) establish national and regional centres of excellence for essential cardiac surgery for the treatment of affected patients and training of cardiovascular practitioners of the future, (6) initiate national multi-sectoral RHD programmes within NCD control programmes of affected countries, and (7) foster international partnerships with multinational organisations for resource mobilisation, monitoring and evaluation of the programme to end RHD in Africa. This Addis Ababa communiqué has since been endorsed by African Union heads of state, and plans are underway to implement the roadmap in order to end ARF and RHD in Africa in our lifetime.