Optimum INR intensity and therapeutic INR control in patients with mechanical heart valve prosthesis on warfarin oral anticoagulation at Dr George Mukhari academic hospital: a three-year retrospective study

Background: Available evidence suggest that the optimum prothrombin time-international normalised ratio (PT-INR) intensities recommended for anticoagulation of patients with mechanical heart valve prosthesis may not apply to all race groups. Optimal PT-INR target ranges and effectiveness of warfarin oral anticoagulation were determined among black South African patients fitted with St Jude bileaflet mechanical heart valve prosthesis  (SJBMHVP) at Dr George Mukhari Academic Hospital (DGMAH).Methods: A convenience sample of 95 medical records of patients fitted with SJBMHVP from 1994 until 2013 was reviewed. Optimum PT-INR target ranges were estimated using two different methods: the classical two PT-INR target level method and the alternative, PT-INR specific incident rate method. The quality of warfarin anticoagulation was assessed using the fraction in therapeutic range method.Results: Optimum PT-INR target ranges for all participants fitted with SJBMHVP in the aortic position was estimated to be 2.0–3.5 and 2.6–3.5, respectively, by the classical and alternative methods. That of the patients with mitral valve replacement was estimated to be in the range 2.6–3.5 by the classical method and that of patients with double heart valve  replacement was estimated to be < 3.5 by both methods. The quality of warfarin anticoagulation of participants with SJBMHVP replacement wasfound to be inadequate as indicated by percentage time in treatment range (TTR) of 49.7% for all study participants compared with the ideal TTR of 70% and above.Conclusion: Optimum Caucasian-based PT-INR intensities recommended for oral anticoagulation of patients fitted with mechanical heart valve prosthesis are applicable to black patients fitted with SJBMHVP at DGMAH.Keywords: black South African patients, heart valve prosthesis, optimal PT-INR, time in treatment range, warfarin oral anticoagulatio

The implementation and utility of clinical exome sequencing in a South African infant cohort

Genetic disorders are significant contributors to infant hospitalization and mortality globally. The early diagnosis of these conditions in infants remains a considerable challenge. Clinical exome sequencing (CES) has shown to be a successful tool for the early diagnosis of genetic conditions, however, its utility in African infant populations has not been investigated. The impact of the under-representation of African genomic data, the cost of testing, and genomic workforce shortages, need to be investigated and evidence-based implementation strategies accounting for locally available genetics expertise and diagnostic infrastructure need to be developed. We evaluated the diagnostic utility of singleton CES in a cohort of 32 ill, South African infants from two State hospitals in Johannesburg, South Africa. We analysed the data using a series of filtering approaches, including a curated virtual gene panel consisting of genes implicated in neonatal-and early childhood-onset conditions and genes with known founder and common variants in African populations. We reported a diagnostic yield of 22% and identified seven pathogenic variants in the NPHS1, COL2A1, OCRL, SHOC2, TPRV4, MTM1 and STAC3 genes. This study demonstrates the utility value of CES in the South African State healthcare setting, providing a diagnosis to patients who would otherwise not receive one and allowing for directed management. We anticipate an increase in the diagnostic yield of our workflow with further refinement of the study inclusion criteria. This study highlights important considerations for the implementation of genomic medicine in under-resourced settings and in under-represented African populations where variant interpretation remains a challenge

Medical Therapies for Uterine Fibroids - A Systematic Review and Network Meta-Analysis of Randomised Controlled Trials

BACKGROUND: Uterine fibroids are common, often symptomatic and a third of women need repeated time off work. Consequently 25% to 50% of women with fibroids receive surgical treatment, namely myomectomy or hysterectomy. Hysterectomy is the definitive treatment as fibroids are hormone dependent and frequently recurrent. Medical treatment aims to control symptoms in order to replace or delay surgery. This may improve the outcome of surgery and prevent recurrence. PURPOSE: To determine whether any medical treatment can be recommended in the treatment of women with fibroids about to undergo surgery and in those for whom surgery is not planned based on currently available evidence. STUDY SELECTION: Two authors independently identified randomised controlled trials (RCT) of all pharmacological treatments aimed at the treatment of fibroids from a list of references obtained by formal search of MEDLINE, EMBASE, Cochrane library, Science Citation Index, and ClinicalTrials.gov until December 2013. DATA EXTRACTION: Two authors independently extracted data from identified studies. DATA SYNTHESIS: A Bayesian network meta-analysis was performed following the National Institute for Health and Care Excellence-Decision Support Unit guidelines. Odds ratios, rate ratios, or mean differences with 95% credible intervals (CrI) were calculated. RESULTS AND LIMITATIONS: A total of 75 RCT met the inclusion criteria, 47 of which were included in the network meta-analysis. The overall quality of evidence was very low. The network meta-analysis showed differing results for different outcomes. CONCLUSIONS: There is currently insufficient evidence to recommend any medical treatment in the management of fibroids. Certain treatments have future promise however further, well designed RCTs are needed

Optimum INR intensity and therapeutic INR control in patients with mechanical heart valve prosthesis on warfarin oral anticoagulation at Dr George Mukhari academic hospital: a three-year retrospective study

Background: Available evidence suggest that the optimum prothrombin time-international normalised ratio (PT-INR) intensities recommended for anticoagulation of patients with mechanical heart valve prosthesis may not apply to all race groups. Optimal PT-INR target ranges and effectiveness of warfarin oral anticoagulation were determined among black South African patients fitted with St Jude bileaflet mechanical heart valve prosthesis (SJBMHVP) at Dr George Mukhari Academic Hospital (DGMAH). Methods: A convenience sample of 95 medical records of patients fitted with SJBMHVP from 1994 until 2013 was reviewed. Optimum PT-INR target ranges were estimated using two different methods: the classical two PT-INR target level method and the alternative, PT-INR specific incident rate method. The quality of warfarin anticoagulation was assessed using the fraction in therapeutic range method.Results: Optimum PT-INR target ranges for all participants fitted with SJBMHVP in the aortic position was estimated to be 2.0–3.5 and 2.6–3.5, respectively, by the classical and alternative methods. That of the patients with mitral valve replacement was estimated to be in the range 2.6–3.5 by the classical method and that of patients with double heart valve replacement was estimated to be 3.5 by both methods. The quality of warfarin anticoagulation of participants with SJBMHVP replacement was found to be inadequate as indicated by percentage time in treatment range (TTR) of 49.7% for all study participants compared with the ideal TTR of 70% and above.Conclusion: Optimum Caucasian-based PT-INR intensities recommended for oral anticoagulation of patients fitted with mechanical heart valve prosthesis are applicable to black patients fitted with SJBMHVP at DGMAH