Browsing by Subject "Case-Control Studies"
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- ItemOpen AccessA case-control study of mesothelioma in South Africa(1995) Rees, David John; Myers, JonnyThis thesis reports the results of a prospective multicentred case-control study of mesothelioma carried out in South Africa. The objectives of the study were: 1) to examine asbestos exposure of cases in detail with respect to source, risk occupations, fibre type and duration; 2) to determine relative risks for level (certainty) of exposure (definite, probable, possible, unlikely), for category of exposure (occupational, environmental), and for fibre type and skin colour; 3) to determine whether cases without recall of exposure were exposed to other non-asbestos putative agents; 4) to investigate the possible protective effect of certain dietary components. Previous studies of mesothelioma in South Africa had, with the exception of one incidence study, focused on particular occupational or case material, exposure data had been gathered in a non-systematic way, often indirectly from surrogates, and non-asbestos agents had not been investigated. In this case-control study these issues are all addressed. In addition, special efforts were made to minimise potential sources of bias (e.g. interviewer bias) and so to furnish reliable effect estimates. The study incorporated the following methodological features: 1) a prospective approach to gather exposure and dietary information directly from the cases and controls in life and so avoid the use of surrogates for this information; 2) the study was multicentred with study teams established in six cities, each with a major referral hospital, to maximise nation-wide coverage; 3) information was gathered with interviewers blind (at least at the beginning of the study) to study objectives and case control status at the time of the interview; 4) rigorous pathologic review was used to establish the diagnosis of mesothelioma; 5) two controls were selected for each case, a cancer and a non-cancer patient matched for hospital, sex, age and skin colour; 6) in analysis the case control datasets were treated separately (i.e cases and cancer controls, and cases and non-cancer controls were treated as two separate datasets). One hundred and twenty three cases were accepted into the study. No case was documented with purely chrysotile exposure nor exposure to a putative non-asbestos cause of the tumour without some evidence of asbestos exposure. A minimum of 22 cases (18%) had exclusively environmental exposure, 20 were from the NW Cape (a crocidolite mining region). Fifty eight percent had occupational exposure, three of whom had mined amosite. The relative risks associated environmental exposure in the NW Cape were larger than for environmental exposure in the NE Transvaal: 21.9 versus 7.1 for the cancer control dataset and 50.9 versus 12.0 for the medical control dataset. Increasing consumption of carotene rich fruit was found to be protective for mesothelioma when adjusted for asbestos exposure. The results confirm the high disease burden due to occupational exposure, the importance of environmental exposure in the crocidolite mining area of the NW Cape, the relative paucity of cases linked to amosite, the rarity of chrysotile cases, and are consistent with the view that there is a fibre gradient in mesotheliomagenic potential for South African asbestos with crocidolite > amosite > chrysotile. The evidence for a protective effect of carotene rich fruit is new in the South African context.
- ItemOpen AccessChildhood tuberculosis is associated with decreased abundance of T cell gene transcripts and impaired T cell function(2017) Hemingway, Cheryl; Berk, Maurice; Anderson, Suzanne T; Wright, Victoria J; Hamilton, Shea; Eleftherohorinou, Hariklia; Goldgof, Greg M; Hickman, Katy; Kampmann, Beate; Schoeman, Johan; Eley, Brian; Beatty, David; Pienaar, Sandra; Nicol, Mark P; Griffiths, Michael J; Waddell, Simon J; Newton, Sandra M; Coin, Lachlan J; Relman, David A; Montana, Giovanni; Levin, MichaelThe WHO estimates around a million children contract tuberculosis (TB) annually with over 80 000 deaths from dissemination of infection outside of the lungs. The insidious onset and association with skin test anergy suggests failure of the immune system to both recognise and respond to infection. To understand the immune mechanisms, we studied genome-wide whole blood RNA expression in children with TB meningitis (TBM). Findings were validated in a second cohort of children with TBM and pulmonary TB (PTB), and functional T-cell responses studied in a third cohort of children with TBM, other extrapulmonary TB (EPTB) and PTB. The predominant RNA transcriptional response in children with TBM was decreased abundance of multiple genes, with 140/204 (68%) of all differentially regulated genes showing reduced abundance compared to healthy controls. Findings were validated in a second cohort with concordance of the direction of differential expression in both TBM (r2 = 0.78 p = 2x10-16) and PTB patients (r2 = 0.71 p = 2x10-16) when compared to a second group of healthy controls. Although the direction of expression of these significant genes was similar in the PTB patients, the magnitude of differential transcript abundance was less in PTB than in TBM. The majority of genes were involved in activation of leucocytes (p = 2.67E-11) and T-cell receptor signalling (p = 6.56E-07). Less abundant gene expression in immune cells was associated with a functional defect in T-cell proliferation that recovered after full TB treatment (p<0.0003). Multiple genes involved in T-cell activation show decreased abundance in children with acute TB, who also have impaired functional T-cell responses. Our data suggest that childhood TB is associated with an acquired immune defect, potentially resulting in failure to contain the pathogen. Elucidation of the mechanism causing the immune paresis may identify new treatment and prevention strategies.
- ItemOpen AccessDevelopment and validation of a short questionnaire to assess sodium intake(2008) Charlton, Karen E; Steyn, Krisela; Levitt, Naomi S; Jonathan, Deborah; Zulu, Jabulisiwe V; Nel, Johanna HOBJECTIVES: To develop and validate a short food-frequency questionnaire to assess habitual dietary salt intake in South Africans and to allow classification of individuals according to intakes above or below the maximum recommended intake of 6 g salt day-1. DESIGN: Cross-sectional validation study in 324 conveniently sampled men and women. METHODS: Repeated 24-hour urinary Na values and 24-hour dietary recalls were obtained on three occasions. Food items consumed by >5% of the sample and which contributed > or =50 mg Na serving-1 were included in the questionnaire in 42 categories. A scoring system was devised, based on Na content of one index food per category and frequency of consumption. RESULTS: Positive correlations were found between Na content of 35 of the 42 food categories in the questionnaire and total Na intake, calculated from 24-hour recall data. Total Na content of the questionnaire was associated with Na estimations from 24-hour recall data (r = 0.750; P < 0.0001; n = 328) and urinary Na (r = 0.152; P = 0.0105; n = 284). Urinary Na was higher for subjects in tertile 3 than tertile 1 of questionnaire Na content (P < 0.05). Questionnaire Na content of <2400 and > or =2400 mg day-1 equated to a reference cut-off score of 48 and corresponded to mean (standard deviation) urinary Na values of 145 (68) and 176 (99) mmol day-1, respectively (P < 0.05). Sensitivity and specificity against urinary Na > or =100 and <100 mmol day-1 was 12.4% and 93.9%, respectively. CONCLUSION: A 42-item food-frequency questionnaire has been shown to have content-, construct- and criterion-related validity, as well as internal consistency, with regard to categorising individuals according to their habitual salt intake; however, the devised scoring system needs to show improved sensitivity.
- ItemOpen AccessErratum to: Investigation of the association between the TCF7L2 rs7903146 (C/T) gene polymorphism and obesity in a Cameroonian population: a pilot study(2017) Nguimmo-Metsadjio, Aurelie; Atogho-Tiedeu, Barbara; Noubiap, Jean Jacques; Evehe, Marie-Solange; Djokam-Dadjeu, Rosine; Donfack, Olivier Sontsa; Nanfa, Dieudonne; Mato, Edith Pascale M; Ngwa, Elvis Ndonwi; Guewo-Fokeng, Magellan; Pokam-Fosso, Priscille; Mbacham, Wilfred F; Mbanya, Jean Claude; Sobngwi, EugèneOBJECTIVE: This study aimed at investigating the association between the rs7903146 (C/T) polymorphism of the TCF7L2 gene with obesity in a Cameroonian population. METHOD: This was a case-control pilot study including 61 obese and 61 non-obese Cameroonian adults. Anthropometric indices of obesity, blood pressure, fasting blood glucose, and blood lipids were measured. The rs7903146 (C/T) polymorphism of the TCF7L2 gene was genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and genotypes were correlated with clinical and biological parameters. RESULTS: The T allele was predominant in the study population with a frequency of 93%. No statistically significant difference was however observed between the genotypic (p = 0.50) and allelic frequencies (p = 0.58) of obese and non-obese subjects. Comparison of clinical and biochemical parameters of C allele carriers (CX = CC + CT) with those of TT genotype showed that there was no significant difference between the lipid profile of these two groups. CONCLUSION: The rs7903146 (C/T) polymorphism of the TCF7L2 gene might not be associated with obesity in the Cameroonian population.
- ItemOpen AccessHIV testing and burden of HIV infection in black cancer patients in Johannesburg, South Africa: a cross-sectional study(2015) Sengayi, Mazvita; Babb, Chantal; Egger, Matthias; Urban, Margaret IBackgroundHIV infection is a known risk factor for cancer but little is known about HIV testing patterns and the burden of HIV infection in cancer patients. We did a cross-sectional analysis to identify predictors of prior HIV testing and to quantify the burden of HIV in black cancer patients in Johannesburg, South Africa.MethodsThe Johannesburg Cancer Case–control Study (JCCCS) recruits newly-diagnosed black cancer patients attending public referral hospitals for oncology and radiation therapy in Johannesburg . All adult cancer patients enrolled into the JCCCS from November 2004 to December 2009 and interviewed on previous HIV testing were included in the analysis. Patients were independently tested for HIV-1 using a single ELISA test . The prevalence of prior HIV testing, of HIV infection and of undiagnosed HIV infection was calculated. Multivariate logistic regression models were fitted to identify factors associated with prior HIV testing.ResultsA total of 5436 cancer patients were tested for HIV of whom 1833[33.7% (95% CI=32.5-35.0)] were HIV-positive. Three-quarters of patients (4092 patients) had ever been tested for HIV. The total prevalence of undiagnosed HIV infection was 11.5% (10.7-12.4) with 34% (32.0–36.3) of the 1833 patients who tested HIV-positive unaware of their infection. Men >49 years [OR 0.49(0.39–0.63)] and those residing in rural areas [OR 0.61(0.39–0.97)] were less likely to have been previously tested for HIV. Men with at least a secondary education [OR 1.79(1.11–2.90)] and those interviewed in recent years [OR 4.13(2.62 – 6.52)] were likely to have prior testing. Women >49 years [OR 0.33(0.27–0.41)] were less likely to have been previously tested for HIV. In women, having children <5 years [OR 2.59(2.04–3.29)], hormonal contraceptive use [OR 1.33(1.09–1.62)], having at least a secondary education [OR:2.08(1.45–2.97)] and recent year of interview [OR 6.04(4.45–8.2)] were independently associated with previous HIV testing.ConclusionsIn a study of newly diagnosed black cancer patients in Johannesburg, over a third of HIV-positive patients were unaware of their HIV status. In South Africa black cancer patients should be targeted for opt-out HIV testing.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1171-7) contains supplementary material, which is available to authorized users.
- ItemOpen AccessHuman newborn bacille Calmette–Guérin vaccination and risk of tuberculosis disease: a case-control study(2016) Fletcher, Helen A; Filali-Mouhim, Ali; Nemes, Elisa; Hawkridge, Anthony; Keyser, Alana; Njikan, Samuel; Hatherill, Mark; Scriba, Thomas J; Abel, Brian; Kagina, Benjamin M; Veldsman, Ashley; Agudelo, Nancy Marín; Kaplan, Gilla; Hussey, Gregory D; Sekaly, Rafick-Pierre; Hanekom, Willem A: An incomplete understanding of the immunological mechanisms underlying protection against tuberculosis (TB) hampers the development of new vaccines against TB. We aimed to define host correlates of prospective risk of TB disease following bacille Calmette-Guérin (BCG) vaccination. : In this study, 5,726 infants vaccinated with BCG at birth were enrolled. Host responses in blood collected at 10 weeks of age were compared between infants who developed pulmonary TB disease during 2 years of follow-up (cases) and those who remained healthy (controls). : Comprehensive gene expression and cellular and soluble marker analysis failed to identify a correlate of risk. We showed that distinct host responses after BCG vaccination may be the reason: two major clusters of gene expression, with different myeloid and lymphoid activation and inflammatory patterns, were evident when all infants were examined together. Cases from each cluster demonstrated distinct patterns of gene expression, which were confirmed by cellular assays. : Distinct patterns of host responses to Mycobacterium bovis BCG suggest that novel TB vaccines may also elicit distinct patterns of host responses. This diversity should be considered in future TB vaccine development.
- ItemOpen AccessIs air pollution a risk factor for rheumatoid arthritis?(2015) Essouma, Mickael; Noubiap, Jean Jacques NRheumatoid arthritis is a chronic inflammatory debilitating disease triggered by a complex interaction involving genetic and environmental factors. Active smoking and occupational exposures such as silica increase its risk, suggesting that initial inflammation and generation of rheumatoid arthritis-related autoantibodies in the lungs may precede the clinical disease. This hypothesis paved the way to epidemiological studies investigating air pollution as a potential determinant of rheumatoid arthritis. Studies designed for epidemiology of rheumatoid arthritis found a link between traffic, a surrogate of air pollution, and this disease. Furthermore, a small case–control study recently found an association between wood smoke exposure and anticyclic citrullinated protein/peptide antibody in sera of patients presenting wood-smoke-related chronic obstructive pulmonary disease. However, reports addressing impact of specific pollutants on rheumatoid arthritis incidence and severity across populations are somewhat conflicting. In addition to the link reported between other systemic autoimmune rheumatic diseases and particulate matters/gaseous pollutants, experimental observation of exacerbated rheumatoid arthritis incidence and severity in mice models of collagen-induced arthritis after diesel exhaust particles exposure as well as hypovitaminosis D-related autoimmunity can help understand the role of air pollution in rheumatoid arthritis. All these considerations highlight the necessity to extend high quality epidemiological researches investigating different sources of atmospheric pollution across populations and particularly in low-and-middle countries, in order to further explore the biological plausibility of air pollution’s effect in the pathogenesis of rheumatoid arthritis. This should be attempted to better inform policies aiming to reduce the burden of rheumatoid arthritis.