Chronic non-communicable diseases in black South African population living in a low-resource community

A thesis submitted to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg in fulfilment of the requirements for the degree of Doctor of Philosophy Johannesburg 2016Introduction: The African continent, particularly sub-Saharan Africa, is facing a high burden of disease from the human immunodeficiency virus (HIV) pandemic and nutritional deficiencies, while at the same time, facing ever increasing rates of cardiovascular diseases (CVDs). The mortality rates from CVD are almost equal to the death rates from communicable diseases. In Sub-Saharan countries CVD prevention and management faces many barriers. One such difficulty is the shortage of data for the descriptive epidemiology of CVD risk factors. In an attempt to address this shortage of data, we established the Heart of Soweto (HOS) study in one of the largest African urban communities in South Africa. The purpose of this study was to identify and describe some of the factors contributing to the emergence of chronic diseases of lifestyle, such as heart disease, high blood pressure, diabetes and obesity in a black urban African population, within the framework of the HOS study. We also investigated the impact of a dietary intervention on cardiac function in subjects with chronic heart failure (CHF) in this black urban cohort. Methods: Data was collected as part of the “Heart of Soweto” (HOS) study, which was a prospectively designed registry that recorded data relating to the presentation, investigation and treatment of patients with newly diagnosed cardiovascular disease presenting to Chris Hani Baragwanath Hospital (CHBH), Soweto in 2006. Data collected included socio-demographic profile and all major cardiovascular diagnoses. Heart disease was defined as non-communicable (ND) e.g. coronary artery disease or communicable (CD) e.g. rheumatic heart disease. A survey was also conducted on consecutive patients attending two pre-selected primary care clinics in Soweto (644 and 667 patients from the Mandela Sisulu and Michael Maponya clinics, respectively). Data collected included, ethnicity, duration of residence in Soweto, highest level of education and employment status. Clinical data collected included prior or current diagnoses of diabetes and hypertension and pharmacological therapy related to the treatment of hypertension, as well as smoking status and exposure to second-hand smoking. Weight, height, and waist and hip circumference were measured. Questions were asked regarding the duration of night-time sleep and napping during the day. Descriptive studies were undertaken at the Heart Failure Clinic at CHBH, Soweto to firstly describe the food choices and macro-and micronutrients intake of 50 consecutive patients presenting with heart failure using an interviewer-administered quantitative food frequency questionnaire (QFFQ). Food data were translated into nutrient data using the Medical Research Council (MRC) Food Finder 3, 2007, which is based on South African food composition tables. Secondly we performed a randomized controlled study of a multidisciplinary, community-based, chronic HF management program in Soweto, compared with usual care, at CHBH Heart Failure Clinic located at the Soweto Cardiovascular Research Unit (SOCRU), or at the General Cardiac ix Clinic (standard care) in Soweto. In this study 49 consenting, eligible patients were individually randomized on a 1:1 basis to either usual care or to the study intervention and cardiac function was measured before and after the intervention. Results: Data collected at Chris Hani Baragwanath hospital (CHBH) cardiology clinic from 5328 suspected cases of heart disease, demonstrated that the most prevalent form of heart disease was hypertensive heart failure (22.0%). It was found that those participants who presented with ND (35.0%) were older and had higher BMI and mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) than those with CD (39.0%; all comparisons p<0.001). Within this cohort of 5328 de novo cases of heart disease, 2505 (47%) were diagnosed with HF, of which 697 (28%) were diagnosed with r i g h t h e a r t f a i l u r e ( RHF). There were more women than men diagnosed with RHF (379 vs. 318 cases), and on an adjusted basis, compared with the remainder of the Heart of Soweto cohort (n = 4631), RHF cases were more likely to be African (adjusted OR 2.33, 95% CI 1.59 – 3.41), with a history of smoking (OR 1.72, 95% CI 1.42 – 2.10), a lower body mass index (OR 0.96, 95% CI 0.94 – 0.97 per kg/m2) and were less likely to have a family history of heart disease (OR 0.79, 95% CI 0.64 – 0.96). Data collected at 2 primary health care clinics in Soweto from 862 women (mean age 41 ± 16 years and mean BMI 29.9 ± 9.2 kg/m2) and 449 men (38 ± 14 years and 24.8 ± 8.3 kg/m2) indicated that in females, former smokers had a higher BMI (p<0.001) than current smokers, while exposure to second hand smoking was associated with a lower BMI (p<0.001) in both genders. Longer sleep duration in females was associated with a lower BMI (p=0.01). Napping during the day for > 30 minutes in males was related to a lower BMI and waist circumference (β=-0.03, p<0.05 for both) and lower systolic (β=-0.02, p<0.05) and diastolic BP (β=-0.02, p<0.05). Longer night time sleep duration was associated with lower diastolic (β=0.004, p<0.01) and systolic BP (β=0.003, p<0.05) in females. Within this same cohort, o b e s i t y w a s m o r e p r e v a l e n t i n f e m a l e s ( 4 1 . 8 % ) t h a n m a l e s ( 1 4 . 1 % ; p < 0 . 0 0 1 ) , 16% (n = 205) had an abnormal 12- lead ECG with more men than women showing a major abnormality (24% vs. 11%; OR 2.63, 95% CI 1.89–3.46). Of 99 cases (7.6%) subject to advanced cardiologic assessment, 29 (2.2%) had newly diagnosed heart disease which included hypertensive heart failure (13 women vs. 2 men, OR 4.51 95% CI 1.00–21.2), coronary artery disease (n = 3), valve disease (n = 3), dilated cardiomyopathy (n = 3) and 2 cases of acute myocarditis. Nutritional deficiencies were observed in a cohort presenting with HF at the cardiology outpatient clinic, CHBH. In women, food choices likely to negatively impact on heart health included added sugar [consumed by 75%: median daily intake (interquartile range) 16 g (10–20)], sweet drinks [54%: 310 ml (85–400)] and salted snacks [61%: 15 g (2–17)]. Corresponding figures for men were added sugar [74%: 15 g (10–15)], sweet drinks [65%: 439 ml (71–670)] and salted snacks [74%: 15 g (4–22)]. The women’s intake of calcium, vitamin C and vitamin E was only 66%, 37% and 40% of the age-specific requirement, respectively. For men, equivalent figures were 66%, 87% and 67%, respectively. Mean sodium intake was 2 372 g/day for men and 1 972 g/day for women, 470 and 294% respectively, of daily recommended intakes (DRI). In men, vitamin C intake was 71 ± 90 (79% of DRI). Similarly, in women vitamin C intake was 66 ± 80 (88% of DRI). Data collected from our HF management programme study supported the deficient intake of vitamin C in African subjects presenting with heart failure. Thus, plasma vitamin C concentrations (normal range 23 – 85 μmol/L) were markedly deficient in both standard care [6.53 (3.80, 9.22) μmol/L] and managed care [3.65 (1.75, 8.23) μmol/L] groups. In terms of clinical presentation, males were significantly older (49.9 ± 10.9 years; p<0.005) than females (37.2 ± 12.8) and at follow-up females had a significantly higher ejection fraction (34.8 ± 9.56 %) than males (29.5 ± 8.27; p<0.05) and when the groups were combined, the ejection fraction was significantly higher (32.2 ± 9.27; p<0.05) at follow-up compared to baseline (29.9 ± 8.80). We found that heart rate was significantly lower at follow-up (89.9 ± 14.6 beats/min) compared to baseline (93.4 ± 17.2; p<0.05) only in the managed care group. Furthermore, if diastolic blood pressure increased over the follow-up period, ejection fraction fell by 5.98% (p=0.009) in comparison to cases where diastolic blood pressure remained the same or fell. In addition, thiamine levels at baseline correlated negatively with systolic blood pressure (r=-0.68, p=0.04) at follow-up. Conclusion: Non-communicable heart disease and other diseases of lifestyle, such as high blood pressure, obesity and diabetes, are drastically increasing in Sub-Saharan Africa in general and in a black urban African community, such as Soweto, specifically. Soweto can clearly be described as a community in epidemiological and nutrition transition and is facing a double or even triple burden of disease. This is a community that is still being burdened by historically prevalent forms of communicable or infectious diseases juxtaposed against people who have lived their whole lives in Soweto and are increasingly suffering from newer or non-communicable diseases of lifestyle. Women seem to be especially burdened by this increase in non-communicable diseases, with a predominance of women suffering from heart disease and obesity. Certain exacerbating risk factors have been identified from the HOS in this community, namely the gender specific effects of sleep, smoking and other environmental factors on BMI and blood pressure, and the adverse effects of changing dietary patterns particularly the increased consumption of refined and processed foods, high in sugar, salt and fats and insufficient intakes of fruits and vegetables. Although there are some limitations to our HF management study, it serves as an indication that targeted, culturally sensitive care, adapted to an urban African population, might contribute to improved patient outcomes. However, prevention should always be our first priority through community-based and gender specific screening and the development and implementation of targeted prevention programs.MT201

Building a global alliance of biofoundries (vol 10, 2040, 2019)

The original version of this Comment contained errors in the legend of Figure 2, in which the locations of the fifteenth and sixteenth GBA members were incorrectly given as '(15) Australian Genome Foundry, Macquarie University; (16) Australian Foundry for Advanced Biomanufacturing, University of Queensland.'. The correct version replaces this with '(15) Australian Foundry for Advanced Biomanufacturing (AusFAB), University of Queensland and (16) Australian Genome Foundry, Macquarie University'. This has been corrected in both the PDF and HTML versions of the Comment

Teaching medical students how to teach: A national survey of students-as-teachers programs in U.S. medical schools

PURPOSE: A number of U.S. medical schools started offering formal students-as-teachers (SAT) training programs to assist medical students in their roles as future teachers. The authors report results of a national survey of such programs in the United States. METHOD: In 2008, a 23-item survey was sent to 130 MD-granting U.S. schools. Responses to selective choice questions were quantitatively analyzed. Open-ended questions about benefits and barriers to SAT programs were given qualitative analyses. RESULTS: Ninety-nine U.S. schools responded. All used their medical students as teachers, but only 44% offered a formal SAT program. Most (95%) offered formal programs in the senior year. Common teaching strategies included small-group work, lectures, role-playing, and direct observation. Common learning content areas were small-group facilitation, feedback, adult learning principles, and clinical skills teaching. Assessment methods included evaluations from student-learners (72%) and direct observation/videotaping (59%). From the qualitative analysis, benefit themes included development of future physician-educators, enhancement of learning, and teaching assistance for faculty. Obstacles were competition with other educational demands, difficulty in faculty recruitment/retention, and difficulty in convincing others of program value. CONCLUSIONS: Formal SAT programs exist for 43 of 99 U.S. medical school respondents. Such programs should be instituted in all schools that use their students as teachers. National teaching competencies, best curriculum methods, and best methods to conduct skills reinforcement need to be determined. Finally, the SAT programs\u27 impacts on patient care, on selection decisions of residency directors, and on residents\u27 teaching effectiveness are areas for future research. Copyright © 2010 by the Association of American Medical Colleges

Genomic medicine and risk prediction across the disease spectrum

Genomic medicine is based on the knowledge that virtually every medical condition, disease susceptibility or response to treatment is caused, regulated or influenced by genes. Genetic testing may therefore add value across the disease spectrum, ranging from single-gene disorders with a Mendelian inheritance pattern to complex multi-factorial diseases. The critical factors for genomic risk prediction are to determine: (1) where the genomic footprint of a particular susceptibility or dysfunction resides within this continuum, and (2) to what extent the genetic determinants are modified by environmental exposures. Regarding the small subset of highly penetrant monogenic disorders, a positive family history and early disease onset are mostly sufficient to determine the appropriateness of genetic testing in the index case and to inform pre-symptomatic diagnosis in at-risk family members. In more prevalent polygenic noncommunicable diseases (NCDs), the use of appropriate eligibility criteria is required to ensure a balance between benefit and risk. An additional screening step may therefore be necessary to identify individuals most likely to benefit from genetic testing. This need provided the stimulus for the development of a pathology-supported genetic testing (PSGT) service as a new model for the translational implementation of genomic medicine in clinical practice. PSGT is linked to the establishment of a research database proven to be an invaluable resource for the validation of novel and previously described gene-disease associations replicated in the South African population for a broad range of NCDs associated with increased cardio-metabolic risk. The clinical importance of inquiry concerning family history in determining eligibility for personalized genotyping was supported beyond its current limited role in diagnosing or screening for monogenic subtypes of NCDs. With the recent introduction of advanced microarray-based breast cancer subtyping, genetic testing has extended beyond the genome of the host to also include tumor gene expression profiling for chemotherapy selection. The decreasing cost of next generation sequencing over recent years, together with improvement of both laboratory and computational protocols, enables the mapping of rare genetic disorders and discovery of shared genetic risk factors as novel therapeutic targets across diagnostic boundaries. This article reviews the challenges, successes, increasing inter-disciplinary integration and evolving strategies for extending PSGT towards exome and whole genome sequencing (WGS) within a dynamic framework. Specific points of overlap are highlighte

Building a global alliance of biofoundries

10.1038/s41467-019-10079-2NATURE COMMUNICATIONS101204

Building a global alliance of biofoundries (vol 10, 2040, 2019)

NATURE COMMUNICATIONS10

Author Correction: Building a global alliance of biofoundries.

The original version of this Comment contained errors in the legend of Figure 2, in which the locations of the fifteenth and sixteenth GBA members were incorrectly given as '(15) Australian Genome Foundry, Macquarie University; (16) Australian Foundry for Advanced Biomanufacturing, University of Queensland.'. The correct version replaces this with '(15) Australian Foundry for Advanced Biomanufacturing (AusFAB), University of Queensland and (16) Australian Genome Foundry, Macquarie University'. This has been corrected in both the PDF and HTML versions of the Comment