| 1. |
- Asiki, Gershim
(författare)
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The survival and nutritional status of children in relation to aspects of maternal health : follow-up studies in rural Uganda
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Low income countries continue to experience high under-five mortality and a high prevalence of protein energy malnutrition (PEM) among surviving children. There is lack of empirical data for accurate tracking of child survival and for determining the consequences of early childhood PEM on future health and education. Main aim: To assess under–five mortality trends and associated factors to inform the design of child survival interventions, and also examine the impact of childhood PEM on future adolescent health and schooling among survivors in a rural population in Uganda. Methods: Four studies were nested in the Kyamulibwa Health and Demographic Surveillance Site in southwestern Uganda. In study 1, prospective data collected between 2002 and 2012 were extracted for 10,118 children under the age of five years and used to estimate age-specific mortality rates using the synthetic cohort life-table method. Calendar year-specific hazard rates and risk factors were explored by Cox regression. In study II, women of reproductive age were enrolled and stillbirth rates were compared using i) 12 months recall of pregnancy outcome (n= 1800) (method 1) and ii) lifetime recall (method 2) and associated risk factors were explored. In study III, 1054 children followed to adolescence were categorised as stunted/wasted, recovered, deteriorated and normal after three nutritional assessments between 1999 and 2011. Mean blood pressures and schooling years achieved measured in 2011 were compared in the 4 groups. In study IV, a pragmatic trial, involving registration of pregnancies and delivering stage-of-pregnancy-specific text message (SMS) via community health workers to pregnant women in 13 intervention villages (n=262) compared with pregnant women in control villages (n=263) with no intervention. Place of birth (home or health facility) was the main outcome. Results: Under-five mortality was 92 per 1000 live births. Overall mortality declined by 33% between 2002 and 2012 with the highest decline observed in the post-neonatal period. Early neonatal mortality did not change. Stillbirth rates differed by method of estimation; 26.2/1000 births versus 13.8/1000 births respectively by methods 1 and 2. No decline in stillbirth rates was observed. Under-five mortality increased with decreasing child age, HIV infection of the child, a birth interval <1 year, having an unmarried mother, a maternal parity >4 and a home delivery. Stillbirth risk increased with maternal age and reduced with increasing parity. In study III, wasting was negatively associated with systolic blood pressure (-7.90 95%CI [-14.52,-1.28], p= 0.02) and diastolic blood pressure (-3.92, 95%CI [-7.42, -0.38], p= 0.03) among surviving children. Recovery from wasting was positively associated with diastolic blood pressure (1.93, 95%CI (0.11, 3.74] p=0.04). Both stunting and wasting regardless of recovery were negatively associated with school achievement. In study IV, the SMS intervention was associated with lower odds of homebirths [AOR=0.38, 95%CI (0.15-0.97)]. Home births were associated with muslim religion [AOR= 4.0, 95%CI (1.72-9.34)], primary or no maternal education [AOR= 2.51, 95%CI (1.00-6.35)] and health facility distance ≥ 2 km [AOR= 2.26, 95%CI (0.95-5.40)]. Conclusions: Survival of children in rural Uganda is improving, and could improve further with increased uptake of family planning and facility births. Promoting community health workers‘ role in improving child survival through use of mobile phones for delivering tailored messages to mothers is a potential strategy that could be scaled up in rural communities.
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| 2. |
- Do, Ron, et al.
(författare)
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Common variants associated with plasma triglycerides and risk for coronary artery disease
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:11, s. 1345-
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Tidskriftsartikel (refereegranskat)abstract
- Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P < 5 x 10(-8) for each) to examine the role of triglycerides in risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, and we show that the direction and magnitude of the associations with both traits are factors in determining CAD risk. Second, we consider loci with only a strong association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol (HDL-C) levels, the strength of a polymorphism's effect on triglyceride levels is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD.
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| 3. |
- Nonterah, Engelbert A., et al.
(författare)
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Racial and Ethnic Differences in the Association Between Classical Cardiovascular Risk Factors and Common Carotid Intima-Media Thickness : An Individual Participant Data Meta-Analysis
- 2022
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Ingår i: Journal of the American Heart Association. - 2047-9980. ; 11:15
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The major risk factors for atherosclerotic cardiovascular disease differ by race or ethnicity but have largely been defined using populations of European ancestry. Despite the rising prevalence of cardiovascular disease in Africa there are few related data from African populations. Therefore, we compared the association of established cardiovascular risk factors with carotid-intima media thickness (CIMT), a subclinical marker of atherosclerosis, between African, African American, Asian, European, and Hispanic populations. METHODS AND RESULTS: Cross-sectional analyses of 34 025 men and women drawn from 15 cohorts in Africa, Asia, Europe, and North America were undertaken. Classical cardiovascular risk factors were assessed and CIMT measured using B-mode ultrasound. Ethnic differences in the association of established cardiovascular risk factors with CIMT were determined using a 2-stage individual participant data meta-analysis with beta coefficients expressed as a percentage using the White population as the reference group. CIMT adjusted for risk factors was the greatest among African American populations followed by Asian, European, and Hispanic populations with African populations having the lowest mean CIMT. In all racial or ethnic groups, men had higher CIMT levels compared with women. Age, sex, body mass index, and systolic blood pressure had a significant positive association with CIMT in all races and ethnicities at varying magnitudes. When compared with European populations, the association of age, sex, and systolic blood pressure with CIMT was weaker in all races and ethnicities. Smoking (beta coeffi-cient, 0.39; 95% CI, 0.09– 0.70), body mass index (beta coefficient, 0.05; 95% CI, 0.01– 0.08) and glucose (beta coefficient, 0.13; 95% CI, 0.06– 0.19) had the strongest positive association with CIMT in the Asian population when compared with all other racial and ethnic groups. High-density lipoprotein-cholesterol had significant protective effects in African American (beta coefficient, −0.31; 95% CI, −0.42 to −0.21) and African (beta coefficient, −0.26; 95% CI, −0.31 to −0.19) populations only. CONCLUSIONS: The strength of association between established cardiovascular risk factors and CIMT differed across the racial or ethnic groups and may be due to lifestyle risk factors and genetics. These differences have implications for race-ethnicity-specific primary prevention strategies and also give insights into the differential contribution of risk factors to the pathogenesis of cardiovascular disease. The greatest burden of subclinical atherosclerosis in African American individuals warrants further investigations.
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| 4. |
- Rawstron, Andy C., et al.
(författare)
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Monoclonal B-cell lymphocytosis in a hospital-based UK population and a rural Ugandan population : a cross-sectional study
- 2017
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Ingår i: The Lancet Haematology. - 2352-3026. ; 4:7, s. E334-E340
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Tidskriftsartikel (refereegranskat)abstract
- Background Reported incidence of B-cell malignancies shows substantial geographical variation, being more common in the Americas and Europe than in Africa. This variation might reflect differences in diagnostic capability, inherited susceptibility, and infectious exposures. Monoclonal B-cell lymphocytosis (MBL) is a precursor lesion that can be screened for in apparently healthy people, allowing comparison of prevalence across different populations independently of health-care provision. We aimed to compare the prevalence and phenotypic characteristics of MBL in age-and-sex-matched populations from rural Uganda and the UK. Methods In this cross-sectional study, we recruited volunteers aged at least 45 years who were seronegative for HIV-1 from the established Ugandan General Population Cohort and obtained their whole-blood samples. We also obtained blood samples from anonymised waste material of age-and-sex-matched individuals (aged >45 years, with a normal blood count and no history of cancer) in the UK. We used flow cytometry to determine the presence of MBL, defined according to standard diagnostic criteria, in the samples and compared differences in the proportion of cases with chronic lymphocytic leukaemia (CLL)-phenotype MBL and CD5-negative MBL, as well as differences in absolute monoclonal B-cell count between the two cohorts. Findings Between Jan 15 and Dec 18, 2012, we obtained samples from 302 Ugandan volunteers and 302 UK individuals who were matched by age and sex to the Ugandan population. Overall MBL prevalence was higher in the Ugandan participants (42 [14%] individuals) than in the UK cohort (25 [8%]; p=0.038). CLL-phenotype MBL was detected in three (1%) Ugandan participants and 21 (7%) UK participants (p=0.00021); all three Ugandan participants had absolute monoclonal B-cell count below one cell per mu L, whereas the 21 UK participants had a median absolute number of circulating neoplastic cells of 4.6 (IQR 2-12) cells per mu L. The prevalence of CD5-negative MBL was higher in the Ugandan cohort (41 [14%], of whom two [5%] also had CLL-phenotype MBL) than in the UK cohort (six [2%], of whom two [33%] also had CLL-phenotype MBL; p<0.0001), but the median absolute B-cell count was similar (227 [IQR 152-345] cells per mu L in the Ugandan cohort vs 135 [105-177] cells per mu L in the UK cohort; p=0.13). Interpretation MBL is common in both Uganda and the UK, but the substantial phenotypic differences might reflect fundamental differences in the pathogenesis of B-cell lymphoproliferative disorders.
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| 6. |
- Wagner, Ryan G., et al.
(författare)
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Estimating the burden of cardiovascular risk in community dwellers over 40 years old in South Africa, Kenya, Burkina Faso and Ghana
- 2021
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Ingår i: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 6:1
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Cardiovascular disease (CVD) risk factors are increasing in sub-Saharan Africa. The impact of these risk factors on future CVD outcomes and burden is poorly understood. We examined the magnitude of modifiable risk factors, estimated future CVD risk and compared results between three commonly used 10-year CVD risk factor algorithms and their variants in four African countries.Methods: In the Africa-Wits-INDEPTH partnership for Genomic studies (the AWI-Gen Study), 10 349 randomly sampled individuals aged 40-60 years from six sites participated in a survey, with blood pressure, blood glucose and lipid levels measured. Using these data, 10-year CVD risk estimates using Framingham, Globorisk and WHO-CVD and their office-based variants were generated. Differences in future CVD risk and results by algorithm are described using kappa and coefficients to examine agreement and correlations, respectively.Results: The 10-year CVD risk across all participants in all sites varied from 2.6% (95% CI: 1.6% to 4.1%) using the WHO-CVD lab algorithm to 6.5% (95% CI: 3.7% to 11.4%) using the Framingham office algorithm, with substantial differences in risk between sites. The highest risk was in South African settings (in urban Soweto: 8.9% (IQR: 5.3-15.3)). Agreement between algorithms was low to moderate (kappa from 0.03 to 0.55) and correlations ranged between 0.28 and 0.70. Depending on the algorithm used, those at high risk (defined as risk of 10-year CVD event >20%) who were under treatment for a modifiable risk factor ranged from 19.2% to 33.9%, with substantial variation by both sex and site.Conclusion: The African sites in this study are at different stages of an ongoing epidemiological transition as evidenced by both risk factor levels and estimated 10-year CVD risk. There is low correlation and disparate levels of population risk, predicted by different risk algorithms, within sites. Validating existing risk algorithms or designing context-specific 10-year CVD risk algorithms is essential for accurately defining population risk and targeting national policies and individual CVD treatment on the African continent.
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| 7. |
- Willer, Cristen J., et al.
(författare)
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Discovery and refinement of loci associated with lipid levels
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:11, s. 1274-1283
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Tidskriftsartikel (refereegranskat)abstract
- Levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and total cholesterol are heritable, modifiable risk factors for coronary artery disease. To identify new loci and refine known loci influencing these lipids, we examined 188,577 individuals using genome-wide and custom genotyping arrays. We identify and annotate 157 loci associated with lipid levels at P < 5 x 10(-8), including 62 loci not previously associated with lipid levels in humans. Using dense genotyping in individuals of European, East Asian, South Asian and African ancestry, we narrow association signals in 12 loci. We find that loci associated with blood lipid levels are often associated with cardiovascular and metabolic traits, including coronary artery disease, type 2 diabetes, blood pressure, waist-hip ratio and body mass index. Our results demonstrate the value of using genetic data from individuals of diverse ancestry and provide insights into the biological mechanisms regulating blood lipids to guide future genetic, biological and therapeutic research.
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