| 1. |
- Johnson, Toby, et al.
(författare)
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Blood Pressure Loci Identified with a Gene-Centric Array.
- 2011
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 1537-6605 .- 0002-9297. ; 89:6, s. 688-700
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Tidskriftsartikel (refereegranskat)abstract
- Raised blood pressure (BP) is a major risk factor for cardiovascular disease. Previous studies have identified 47 distinct genetic variants robustly associated with BP, but collectively these explain only a few percent of the heritability for BP phenotypes. To find additional BP loci, we used a bespoke gene-centric array to genotype an independent discovery sample of 25,118 individuals that combined hypertensive case-control and general population samples. We followed up four SNPs associated with BP at our p < 8.56× 10(-7) study-specific significance threshold and six suggestively associated SNPs in a further 59,349 individuals. We identified and replicated a SNP at LSP1/TNNT3, a SNP at MTHFR-NPPB independent (r(2) = 0.33) of previous reports, and replicated SNPs at AGT and ATP2B1 reported previously. An analysis of combined discovery and follow-up data identified SNPs significantly associated with BP at p < 8.56× 10(-7) at four further loci (NPR3, HFE, NOS3, and SOX6). The high number of discoveries made with modest genotyping effort can be attributed to using a large-scale yet targeted genotyping array and to the development of a weighting scheme that maximized power when meta-analyzing results from samples ascertained with extreme phenotypes, in combination with results from nonascertained or population samples. Chromatin immunoprecipitation and transcript expression data highlight potential gene regulatory mechanisms at the MTHFR and NOS3 loci. These results provide candidates for further study to help dissect mechanisms affecting BP and highlight the utility of studying SNPs and samples that are independent of those studied previously even when the sample size is smaller than that in previous studies.
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| 2. |
- Jacobs, Eric J, et al.
(författare)
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Family history of cancer and risk of pancreatic cancer : A pooled analysis from the Pancreatic Cancer Cohort Consortium (PanScan).
- 2010
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215.
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Tidskriftsartikel (refereegranskat)abstract
- A family history of pancreatic cancer has consistently been associated with increased risk of pancreatic cancer. However, uncertainty remains about the strength of this association. Results from previous studies suggest a family history of select cancers (i.e., ovarian, breast and colorectal) could also be associated, although not as strongly, with increased risk of pancreatic cancer. We examined the association between a family history of 5 types of cancer (pancreas, prostate, ovarian, breast and colorectal) and risk of pancreatic cancer using data from a collaborative nested case-control study conducted by the Pancreatic Cancer Cohort Consortium. Cases and controls were from cohort studies from the United States, Europe and China, and a case-control study from the Mayo Clinic. Analyses of family history of pancreatic cancer included 1,183 cases and 1,205 controls. A family history of pancreatic cancer in a parent, sibling or child was associated with increased risk of pancreatic cancer [multivariate-adjusted odds ratios (ORs) = 1.76, 95% confidence interval (CI) = 1.19-2.61]. A family history of prostate cancer was also associated with increased risk (OR = 1.45, 95% CI = 1.12-1.89). There were no statistically significant associations with a family history of ovarian cancer (OR = 0.82, 95% CI = 0.52-1.31), breast cancer (OR = 1.21, 95% CI = 0.97-1.51) or colorectal cancer (OR = 1.17, 95% CI = 0.93-1.47). Our results confirm a moderate sized association between a family history of pancreatic cancer and risk of pancreatic cancer and also provide evidence for an association with a family history of prostate cancer worth further study.
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| 3. |
- Ibinda, Fredrick, et al.
(författare)
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Burden of epilepsy in rural Kenya measured in disability-adjusted life years
- 2014
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Ingår i: Epilepsia. - : John Wiley & Sons. - 0013-9580 .- 1528-1167. ; 55:10, s. 1626-1633
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Tidskriftsartikel (refereegranskat)abstract
- ObjectivesThe burden of epilepsy, in terms of both morbidity and mortality, is likely to vary depending on the etiology (primary [genetic/unknown] vs. secondary [structural/metabolic]) and with the use of antiepileptic drugs (AEDs). We estimated the disability-adjusted life years (DALYs) and modeled the remission rates of active convulsive epilepsy (ACE) using epidemiologic data collected over the last decade in rural Kilifi, Kenya.MethodsWe used measures of prevalence, incidence, and mortality to model the remission of epilepsy using disease-modeling software (DisMod II). DALYs were calculated as the sum of Years Lost to Disability (YLD) and Years of Life Lost (YLL) due to premature death using the prevalence approach, with disability weights (DWs) from the 2010 Global Burden of Disease (GBD) study. DALYs were calculated with R statistical software with the associated uncertainty intervals (UIs) computed by bootstrapping.ResultsA total of 1,005 (95% UI 797-1,213) DALYs were lost to ACE, which is 433 (95% UI 393-469) DALYs lost per 100,000 people. Twenty-six percent (113/100,000/year, 95% UI 106-117) of the DALYs were due to YLD and 74% (320/100,000/year, 95% UI 248-416) to YLL. Primary epilepsy accounted for fewer DALYs than secondary epilepsy (98 vs. 334 DALYs per 100,000 people). Those taking AEDs contributed fewer DALYs than those not taking AEDs (167 vs. 266 DALYs per 100,000 people). The proportion of people with ACE in remission per year was estimated at 11.0% in males and 12.0% in females, with highest rates in the 0-5year age group.SignificanceThe DALYs for ACE are high in rural Kenya, but less than the estimates of 2010 GBD study. Three-fourths of DALYs resulted from secondary epilepsy. Use of AEDs was associated with 40% reduction of DALYs. Improving adherence to AEDs may reduce the burden of epilepsy in this area.
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| 4. |
- Jack, Helen, et al.
(författare)
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Closing the mental health treatment gap in South Africa : a review of costs and cost-effectiveness
- 2014
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Ingår i: Global Health Action. - : Informa UK Limited. - 1654-9716 .- 1654-9880. ; 7, s. 137-147
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Tidskriftsartikel (refereegranskat)abstract
- Background: Nearly one in three South Africans will suffer from a mental disorder in his or her lifetime, a higher prevalence than many low- and middle-income countries. Understanding the economic costs and consequences of prevention and packages of care is essential, particularly as South Africa considers scaling-up mental health services and works towards universal health coverage. Economic evaluations can inform how priorities are set in system or spending changes.Objective: To identify and review research from South Africa and sub-Saharan Africa on the direct and indirect costs of mental, neurological, and substance use (MNS) disorders and the cost-effectiveness of treatment interventions.Design: Narrative overview methodology.Results and conclusions: Reviewed studies indicate that integrating mental health care into existing health systems may be the most effective and cost-efficient approach to increase access to mental health services in South Africa. Integration would also direct treatment, prevention, and screening to people with HIV and other chronic health conditions who are at high risk for mental disorders. We identify four major knowledge gaps: 1) accurate and thorough assessment of the health burdens of MNS disorders, 2) design and assessment of interventions that integrate mental health screening and treatment into existing health systems, 3) information on the use and costs of traditional medicines, and 4) cost-effectiveness evaluation of a range of specific interventions or packages of interventions that are tailored to the national context.
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| 5. |
- Kamuyu, Gathoni, et al.
(författare)
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Exposure to Multiple Parasites Is Associated with the Prevalence of Active Convulsive Epilepsy in Sub-Saharan Africa
- 2014
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Ingår i: PLoS Neglected Tropical Diseases. - : Public Library of Science (PLoS). - 1935-2727 .- 1935-2735. ; 8:5
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Tidskriftsartikel (refereegranskat)abstract
- Background: Epilepsy is common in developing countries, and it is often associated with parasitic infections. We investigated the relationship between exposure to parasitic infections, particularly multiple infections and active convulsive epilepsy (ACE), in five sites across sub-Saharan Africa. Methods and Findings: A case-control design that matched on age and location was used. Blood samples were collected from 986 prevalent cases and 1,313 age-matched community controls and tested for presence of antibodies to Onchocerca volvulus, Toxocara canis, Toxoplasma gondii, Plasmodium falciparum, Taenia solium and HIV. Exposure (seropositivity) to Onchocerca volvulus (OR = 1.98; 95% CI: 1.52-2.58, p<0.001), Toxocara canis (OR = 1.52; 95% CI: 1.23-1.87, p<0.001), Toxoplasma gondii (OR = 1.28; 95% CI: 1.04-1.56, p=0.018) and higher antibody levels (top tertile) to Toxocara canis (OR = 1.70; 95% CI: 1.30-2.24, p<0.001) were associated with an increased prevalence of ACE. Exposure to multiple infections was common (73.8% of cases and 65.5% of controls had been exposed to two or more infections), and for T. gondii and O. volvulus co-infection, their combined effect on the prevalence of ACE, as determined by the relative excess risk due to interaction (RERI), was more than additive (T. gondii and O. volvulus, RERI = 1.19). The prevalence of T. solium antibodies was low (2.8% of cases and 2.2% of controls) and was not associated with ACE in the study areas. Conclusion: This study investigates how the degree of exposure to parasites and multiple parasitic infections are associated with ACE and may explain conflicting results obtained when only seropositivity is considered. The findings from this study should be further validated.
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| 6. |
- Newton, Charles R., et al.
(författare)
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Infectious causes of epilepsy?
- 2014. - 1
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Ingår i: Neglected tropical diseases and conditions of the nervous system. - New York : Springer. - 9781461481003 - 9781461480990 ; , s. 355-367
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Bokkapitel (refereegranskat)abstract
- Epilepsy occurs throughout the world, and the prevalence appears to be higher in areas in which the incidence of infections of the central nervous system (CNS) is greater. However, establishing the causal relationship between infections and the development of epilepsy is difficult, since epilepsy occurs a variable period after an acute infection. In addition to this, not all people with chronic infestations of parasites develop epilepsy. We discuss possible CNS infections, particularly the neglected diseases associated with epilepsy, looking at possible mechanisms of epileptogenesis.
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| 7. |
- Ngugi, Anthony K., et al.
(författare)
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Prevalence of active convulsive epilepsy in sub-Saharan Africa and associated risk factors : cross-sectional and case-control studies
- 2013
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Ingår i: Lancet Neurology. - 1474-4422 .- 1474-4465. ; 12:3, s. 253-263
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Tidskriftsartikel (refereegranskat)abstract
- Background The prevalence of epilepsy in sub-Saharan Africa seems to be higher than in other parts of the world, but estimates vary substantially for unknown reasons. We assessed the prevalence and risk factors of active convulsive epilepsy across five centres in this region. Methods We did large population-based cross-sectional and case-control studies in five Health and Demographic Surveillance System centres: Kilifi, Kenya (Dec 3, 2007-July 31, 2008); Agincourt, South Africa (Aug 4, 2008-Feb 27, 2009); Iganga-Mayuge, Uganda (Feb 2, 2009-Oct 30, 2009); Ifakara, Tanzania (May 4, 2009-Dec 31, 2009); and Kintampo, Ghana (Aug 2, 2010-April 29, 2011). We used a three-stage screening process to identify people with active convulsive epilepsy. Prevalence was estimated as the ratio of confirmed cases to the population screened and was adjusted for sensitivity and attrition between stages. For each case, an age-matched control individual was randomly selected from the relevant centre's census database. Fieldworkers masked to the status of the person they were interviewing administered questionnaires to individuals with active convulsive epilepsy and control individuals to assess sociodemographic variables and historical risk factors (perinatal events, head injuries, and diet). Blood samples were taken from a randomly selected subgroup of 300 participants with epilepsy and 300 control individuals from each centre and were screened for antibodies to Toxocara canis, Toxoplasma gondii, Onchocerca volvulus, Plasmodium falciparum, Taenia solium, and HIV. We estimated odds ratios (ORs) with logistic regression, adjusted for age, sex, education, employment, and marital status. Results 586 607 residents in the study areas were screened in stage one, of whom 1711 were diagnosed as having active convulsive epilepsy. Prevalence adjusted for attrition and sensitivity varied between sites: 7.8 per 1000 people (95% CI 7.5-8.2) in Kilifi, 7.0 (6.2-7.4) in Agincourt, 10.3 (9.5-11.1) in Iganga-Mayuge, 14.8 (13.8-15.4) in Ifakara, and 10.1 (9.5-10.7) in Kintampo. The 1711 individuals with the disorder and 2032 control individuals were given questionnaires. In children (aged <18 years), the greatest relative increases in prevalence were associated with difficulties feeding, crying, or breathing after birth (OR 10.23, 95% CI 5 85-1788; p<0.0001); abnormal antenatal periods (2.15, 1.53-3.02; p<0.0001); and head injury (1.97, 1.28-3.03; p=0.002). In adults (aged >= 18 years), the disorder was significantly associated with admission to hospital with malaria or fever (2.28, 1.06-4.92; p=0.036), exposure to T canis (1.74, 1.27-2.40; p=0.0006), exposure to T gondii (1.39, 1.05-1.84; p=0.021), and exposure to 0 volvulus (2.23, 1.56-3.19; p<0.0001). Hypertension (2.13, 1.08-4.20; p=0.029) and exposure to T solium (7.03, 2.06-24.00; p=0.002) were risk factors for adult-onset disease. Interpretation The prevalence of active convulsive epilepsy varies in sub-Saharan Africa and that the variation is probably a result of differences in risk factors. Programmes to control parasitic diseases and interventions to improve antenatal and perinatal care could substantially reduce the prevalence of epilepsy in this region.
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| 8. |
- Wagner, Ryan G., et al.
(författare)
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Prevalence and risk factors for active convulsive epilepsy in rural northeast South Africa
- 2014
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Ingår i: Epilepsy Research. - : Elsevier BV. - 0920-1211 .- 1872-6844. ; 108:4, s. 782-791
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Tidskriftsartikel (refereegranskat)abstract
- Rationale: Epilepsy is among the most common neurological disorders there are few large, population-based studies of the prevalence and risk southern Africa. Methods: From August 2008 to February 2009, as part of a multi-site study, we undertook a three-stage, population-based study, embedded within the Agincourt health and socio-demographic surveillance system, to estimate the prevalence and identify risk factors of active convulsive epilepsy (ACE) in a rural South African population. Results: The crude prevalence of ACE, after adjusting for non-response and the sensitivity of the screening method, was 7.0/1,000 individuals (95%CI 6.4-7.6) with significant geographic heterogeneity across the study area. Being male (OR= 2.3; 95%CI 1.6-3.2), family history of seizures (OR =4.0; 95%CI 2.0-8.1), a sibling with seizures (OR = 7.0; 95%CI 1.6-31.7), problems after delivery (OR= 5.9; 95%CI 1.2-24.6), and history of snoring (OR =6.5; 95%CI 4.5-9.5) were significantly associated with ACE. For children, their mother's exposure to some formal schooling was protective (OR = 0.30; 95%CI 0.11-0.84) after controlling for age and sex. Human immunodeficiency virus was not found to be associated with ACE. Conclusions: ACE is less frequent in this part of rural South Africa than other parts of sub-Saharan Africa. Improving obstetric services could prevent epilepsy. The relationship between snoring and ACE requires further investigation, as does the relative contribution of genetic and environmental factors to examine the increased risk in those with a family history of epilepsy. (C) 2014 Elsevier B.V. All rights reserved.
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