Browsing by Author "Mayosi, Bongani M."
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- ItemArrhythmogenic right ventricular cardiomyopathy type 6 (ARVC6) : support for the locus assignment, narrowing of the critical region and mutation screening of three candidate genes(BioMed Central, 2006-03) Matolweni, Luzuko O.; Bardien, Soraya; Rebello, George; Oppon, Ekow; Munclinger, Miroslav; Ramesar, Rajkumar; Watkins, Hugh; Mayosi, Bongani M.Background: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a heritable disorder characterized by progressive degeneration of right ventricular myocardium, arrhythmias and an increased risk of sudden death at a young age. By linkage analysis, ARVC type 6 was previously mapped to a 10.6 cM region on chromosome 10p12-p14 in a large North American kindred. To date, the genetic defect that causes ARVC6 has not been identified. Methods: We identified a South African family of 13 members with ARVC segregating as an autosomal dominant disorder. The diagnosis of ARVC was based on international diagnostic criteria. All available family members were genotyped with microsatellite markers at six known ARVC loci, and positional candidate gene screening was performed. Results: Genetic linkage and haplotype analysis provided lod scores that are highly suggestive of linkage to the ARVC6 locus on chromosome 10p12-p14, and the narrowing of the critical region to ~2.9 Mb. Two positional candidate genes (ITG8 and FRMD4A) were screened in which defects could possibly disrupt cell-cell adhesion. A non-positional candidate gene with apoptosis inducing properties, LAMR1P6 (laminin receptor 1 pseudogene 6) was also screened. Direct sequencing of DNA from affected individuals failed to detect disease-causing mutations in the exonic sequences of the three genes investigated. Conclusion: The narrowing of the ARVC6 critical region may facilitate progress towards the identification of the gene that is involved in ARVC. Identification of the causative genes for ARVC will contribute to the understanding of the pathogenesis and management of this poorly understood condition.
- ItemBurden of non-communicable diseases in sub-Saharan Africa, 1990–2017 : results from the Global Burden of Disease Study 2017(Elsevier, 2019-10) Gouda, Hebe N.; Charlson, Fiona; Sorsdahl, Katherine; Ahmadzada, Sanam; Ferrari, Alize J.; Erskine, Holly; Leung, Janni; Santamauro, Damian; Lund, Crick; Aminde, Leopold Ndemnge; Mayosi, Bongani M.; Kengne, Andre Pascal; Harris, Meredith; Achoki, Tom; Wiysonge, Charles S.; Stein, Dan J.; Whiteford, HarveyBackground: Although the burden of disease in sub-Saharan Africa continues to be dominated by infectious diseases, countries in this region are undergoing a demographic transition leading to increasing prevalence of noncommunicable diseases (NCDs). To inform health system responses to these changing patterns of disease, we aimed to assess changes in the burden of NCDs in sub-Saharan Africa from 1990 to 2017. Methods: We used data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 to analyse the burden of NCDs in sub-Saharan Africa in terms of disability-adjusted life-years (DALYs)—with crude counts as well as all-age and age-standardised rates per 100000 population—with 95% uncertainty intervals (UIs). We examined changes in burden between 1990 and 2017, and differences across age, sex, and regions. We also compared the observed NCD burden across countries with the expected values based on a country’s Socio-demographic Index. Findings: All-age total DALYs due to NCDs increased by 67·0% between 1990 (90·6 million [95% UI 81·0–101·9]) and 2017 (151·3 million [133·4–171·8]), reflecting an increase in the proportion of total DALYs attributable to NCDs (from 18·6% [95% UI 17·1–20·4] to 29·8% [27·6–32·0] of the total burden). Although most of this increase can be explained by population growth and ageing, the age-standardised DALY rate (per 100000 population) due to NCDs in 2017 (21757·7 DALYs [95% UI 19 377·1–24380·7]) was almost equivalent to that of communicable, maternal, neonatal, and nutritional diseases (26491·6 DALYs [25165·2–28129·8]). Cardiovascular diseases were the second leading cause of NCD burden in 2017, resulting in 22·9 million (21·5–24·3) DALYs (15·1% of the total NCD burden), after the group of disorders categorised as other NCDs (28·8 million [25·1–33·0] DALYs, 19·1%). These categories were followed by neoplasms, mental disorders, and digestive diseases. Although crude DALY rates for all NCDs have decreased slightly across sub-Saharan Africa, age-standardised rates are on the rise in some countries (particularly those in southern sub-Saharan Africa) and for some NCDs (such as diabetes and some cancers, including breast and prostate cancer). Interpretation: NCDs in sub-Saharan Africa are posing an increasing challenge for health systems, which have to date largely focused on tackling infectious diseases and maternal, neonatal, and child deaths. To effectively address these changing needs, countries in sub-Saharan Africa require detailed epidemiological data on NCDs.
- ItemClinical characteristics and initial management of patients with tuberculous pericarditis in the HIV era : the investigation of the management of Pericarditis in Africa (IMPI Africa) registry(BioMed Central, 2006-01) Mayosi, Bongani M.; Wiysonge, Charles Shey; Ntsekhe, Mpiko; Volmink, Jimmy A.; Gumedze, Freedom; Maartens, Gary; Aje, Akinyemi; Thomas, Baby M.; Thomas, Kandathil M.; Awotedu, Abolade A.; Thembela, Bongani; Mntla, Phindile; Maritz [Late], Frans; Ngu Blackett, Kathleen; Nkouonlack, Duquesne C.; Burch, Vanessa C.; Rebe, Kevin; Parish, Andy; Sliwa, Karen; Vezi, Brian Z.; Alam, Nowshad; Brown, Basil G.; Gould, Trevor; Visser, Tim; Shey, Muki S.; Magula, Nombulelo P.; Commerford, Patrick J.Background: The incidence of tuberculous pericarditis has increased in Africa as a result of the human immunodeficiency virus (HIV) epidemic. However, the effect of HIV co-infection on clinical features and prognosis in tuberculous pericarditis is not well characterised. We have used baseline data of the Investigation of the Management of Pericarditis in Africa (IMPI Africa) registry to assess the impact of HIV co-infection on clinical presentation, diagnostic evaluation, and treatment of patients with suspected tuberculous pericarditis in sub-Saharan Africa. Methods: Consecutive adult patients in 15 hospitals in three countries in sub-Saharan Africa were recruited on commencement of treatment for tuberculous pericarditis, following informed consent. We recorded demographic, clinical, diagnostic and therapeutic information at baseline, and have used the chi-square test and analysis of variance to assess probabilities of significant differences (in these variables) between groups defined by HIV status. Results: A total of 185 patients were enrolled from 01 March 2004 to 31 October 2004, 147 (79.5%) of whom had effusive, 28 (15.1%) effusive-constrictive, and 10 (5.4%) constrictive or acute dry pericarditis. Seventy-four (40%) had clinical features of HIV infection. Patients with clinical HIV disease were more likely to present with dyspnoea (odds ratio [OR] 3.2, 95% confidence interval [CI] 1.4 to 7.4, P = 0.005) and electrocardiographic features of myopericarditis (OR 2.8, 95% CI 1.1 to 6.9, P = 0.03). In addition to electrocardiographic features of myopericarditis, a positive HIV serological status was associated with greater cardiomegaly (OR 3.89, 95% CI 1.34 to 11.32, P = 0.01) and haemodynamic instability (OR 9.68, 95% CI 2.09 to 44.80, P = 0.0008). However, stage of pericardial disease at diagnosis and use of diagnostic tests were not related to clinical HIV status. Similar results were obtained for serological HIV status. Most patients were treated on clinical grounds, with microbiological evidence of tuberculosis obtained in only 13 (7.0%) patients. Adjunctive corticosteroids were used in 109 (58.9%) patients, with patients having clinical HIV disease less likely to be put on them (OR 0.37, 95% CI 0.20 to 0.68). Seven patients were on antiretroviral drugs. Conclusion Patients with suspected tuberculous pericarditis and HIV infection in Africa have greater evidence of myopericarditis, dyspnoea, and haemodynamic instability. These findings, if confirmed in other studies, may suggest more intensive management of the cardiac disease is warranted in patients with HIV-associated pericardial disease.
- ItemThe efficacy and safety of complete pericardial drainage by means of intrapericardial fibrinolysis for the prevention of complications of pericardial effusion : a systematic review protocol(BMJ Publishing Group, 2016) Kakia, Aloysious; Wiysonge, Charles S.; Ochodo, Eleanor A.; Awotedu, Abolade A.; Ristic, Arsen D.; Mayosi, Bongani M.ENGLISH SUMMARY : Introduction: Intrapericardial fibrinolysis has been proposed as a means of preventing complications of pericardial effusion such as cardiac tamponade, persistent and recurrent pericardial effusion, and pericardial constriction. There is a need to understand the efficacy and safety of this procedure because it shows promise. Methods and analysis: We aim to assess the effects of intrapericardial fibrinolysis in the treatment of pericardial effusion. We will search PubMed, the Cochrane Library, African Journals online, Cumulative Index to Nursing and Allied Health Literature, Trip database, Clinical trials.gov and the WHO International Clinical Trials Registry Platform for studies that evaluate the efficacy and/or safety of complete pericardial fluid drainage by intrapericardial fibrinolysis irrespective of study design, geographical location, language, age of participants, aetiology of pericarditis or types of fibrinolytics. Two authors will do the search independently, screen the search outputs for potentially eligible studies and assess whether the studies meet the inclusion criteria. Discrepancies between the two authors will be resolved through discussion and arbitration by a third author. Data from the selected studies shall be extracted using a standardised data collection form which will be piloted before use. The methodological quality of studies will be assessed using the Cochrane Collaboration’s tools for assessing risk of bias for experimental studies and non-randomised studies, respectively. The primary meta- analysis will use random effects models due to expected interstudy heterogeneity. Dichotomous data will be analysed using relative risk and continuous with data mean differences, both with 95% CIs.
- ItemHistory of medicine : the Hamilton Naki Clinical Scholarship, 2007-2011(Health and Medical Publishing Group (HMPG), 2012-01) Madiba, Thandinkosi E.; Awotedu, Abolade A.; Du Plessis, Dion; Nchabeleng, Maphoshane; Sathekge, Mike M.; Velaphi, Sithembiso C.; Volmink, Jimmy A.; Walubo, Andrew; Mayosi, Bongani M.The Hamilton Naki Scholarship was introduced because of the shortage of qualified academic leaders in South African medical schools, especially for academic clinicians from previously disadvantaged backgrounds. There were only a handful of African academic doctors with a significant published record of scholarship in South Africa. If academic physicians from the whole population were not recruited and trained, South Africa would lose its ability to train high-quality health practitioners. To address these deficiencies, the Netcare Physician Partnerships Trust established a scholarship to produce world-class academics in all medical specialties to teach and conduct research comparable to other parts of the world.
- ItemHIV infection is associated with a lower incidence of constriction in presumed tuberculous pericarditis : a prospective observational study(Public Library of Science (PLOS), 2008-04) Ntsekhe, Mpiko; Wiysonge, Charles S.; Gumedze, Freedom; Maartens, Gary; Commerford, Patrick J.; Volmink, Jimmy A.; Mayosi, Bongani M.Background: Pericardial constriction is a serious complication of tuberculous pericardial effusion that occurs in up to a quarter of patients despite anti-tuberculosis chemotheraphy. The impact of human immunodeficiency virus (HIV) infection on the incidence of constrictive pericarditis following tuberculous pericardial effusion is unknown. Methods and Results: We conducted a prospective observational study to determine the association between HIV infection and the incidence of constrictive pericarditis among 185 patients (median age 33 years) with suspected tuberculous pericardial effusion. These patients were recruited consecutively between March and October 2004 on commencement of anti-tuberculosis treatment, from 15 hospitals in Cameroon, Nigeria and South Africa. Surviving patients (N = 119) were assessed for clinical evidence of constrictive pericarditis at 3 and 6 months of follow-up. Clinical features of HIV infection were present in 42 (35.2%) of the 119 patients at enrolment into the study.66 of the 119 (56.9%) patients consented to HIV testing at enrolment. During the 6 months of follow-up, a clinical diagnosis of constrictive pericarditis was made in 13 of the 119 patients (10.9%, 95% confidence interval [CI] 5.9-18%). Patients with clinical features of HIV infection appear less likely to develop constriction than those without (4.8% versus 14.3%; P = 0.08). None of the 33 HIV seropositive patients developed constriction, but 8 (24.2%, 95%CI 11.1-42.3%)of the 33 HIV seronegative patients did (P = 0.005). In a multivariate logistic regression model adjusting simultaneously for several baseline characteristics, only clinical signs of HIV infection were significantly associated with a lower risk of constriction (odd ratio 0.14, 95% CI 0.02-0.87, P = 0.035). Conclusions: These data suggest that HIV infection is associated with a lower incidence of pericardial constriction in patients with presumed tuberculous pericarditis. © 2008 Ntsekhe et al.
- ItemQuality of abstracts of pilot trials in heart failure : a protocol for a systematic survey(Elsevier, 2017) Isiguzo, Godsent; Zunza, Moleen; Chirehwa, Maxwell; Mayosi, Bongani M.; Thabane, LehanaIntroduction: Pilot trials are initial small-scale studies done to inform the design of larger trials. Their findings like other studies are usually disseminated as peer-reviewed journal articles. Abstracts are used to introduce the contents to readers, and give a general idea about the full reports and sometimes are the only source of information available to readers. Despite their importance, the contents of abstracts of trial reports are usually not informative enough and lack the essential details. Methods and analysis: This is a protocol for a planned systematic survey with a primary aim of analyzing the reporting quality measured as the completeness of the reporting of pilot trial abstracts in heart failure. The secondary aim will be to explore factors associated with better reporting quality. Abstracts of heart failure pilot trials in humans (journal and conference abstracts) published in the English language from 1 January 1990 to 30 November 2016 will be assessed to determine the reporting quality, based on the CONSORT 2010 statement extension to randomized pilot and feasibility trials. All non-pilot/feasibility trials and non-human pilot trials will be excluded. We will search Medline (PUBMED), Cochrane controlled trials register, Scopus and African wide information databases for pilot trials in heart failure. Title and abstracts of identified studies will be screened for inclusion and data extracted independently by two reviewers in duplicate without using the full text. Reported and unreported items on the abstracts will be presented as frequencies and percentages, a descriptive analysis will be used to interpret the reporting quality and regression analysis used for characteristics associated with greater statistical reporting at 95% confidence interval.
- ItemQuality of pilot trial abstracts in heart failure is suboptimal : a systematic survey(BioMed Central, 2018-05-31) Isiguzo, Godsent C.; Zunza, Moleen; Chirehwa, Maxwell; Mayosi, Bongani M.; Thabane, LehanaBackground: Pilot trials are miniature researches carried out with the sole aim of acting as the precursor for larger more definitive studies. Abstracts are used to summarize and introduce the findings to the reading audience. There is substantive empirical evidence showing that abstracts, despite their important roles, are not informative enough, lacking the necessary details. This systematic survey was designed to assess the quality of reporting of heart failure pilot trial abstracts. The quality of reporting was defined as the completeness of reporting based on adherence to the CONSORT extension for reporting of pilot trial abstracts. We also identified factors associated with reporting quality. Methods: We searched MEDLINE (PubMed), Cochrane Controlled Trials Register, Scopus, and African-wide information databases for abstracts from heart failure pilot trials in humans published from 1 January 1990 to 30 November 2016. These were assessed to determine the extent of adherence to CONSORT extension checklist for reporting of abstracts of pilot trials. We screened identified studies for inclusion based on title and abstract. Data were independently extracted by two reviewers using the checklist. We used regression analysis to assess the association between completeness of reporting (measured as the number of items in the CONSORT extension checklist for reporting of abstracts in pilot trials contained in each abstract) and factors influencing the quality of the reports. Results: Two hundred and twenty-eight (228) articles were retrieved, of which 92 met the inclusion criteria. The mean CONSORT extension score was 8.3/16 (standard deviation 1.7); the least reported items were the source of funding (1% [1/92]), trial registration (13% [12/92]), randomization sequence (13% [12/92]), number randomized to each arm (16% [15/92]), and number analyzed in each arm (16% [15/92]). Multivariable regression analysis showed that pharmacological intervention pilot trials [incidence rate ratio (IRR) = 0.88; 95% confidence interval (CI), 0.81–0.97] were significantly associated with better reporting. Other factors such as structured abstract (IRR = 1.10; 95% CI, 0.99–1.23) and CONSORT endorsement (IRR = 1.10; 95% CI, 0.99–1.23) only showed minimal relationship with better reporting quality. Conclusion: The quality of reporting of abstracts of heart failure pilot trials was suboptimal. Pharmacological intervention was significantly associated with better reporting. These findings are consistent with previous research on reporting of trials.