| 1. |
- Li, Josephine H., et al.
(författare)
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Identification of Genetic Variation Influencing Metformin Response in a Multiancestry Genome-Wide Association Study in the Diabetes Prevention Program (DPP)
- 2023
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 72:8, s. 1161-1172
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide significant loci for metformin response in type 2 diabetes reported elsewhere have not been repli-cated in the Diabetes Prevention Program (DPP). To as-sess pharmacogenetic interactions in prediabetes, we conducted a genome-wide association study (GWAS) in the DPP. Cox proportional hazards models tested associations with diabetes incidence in the metformin (MET; n = 876) and placebo (PBO; n = 887) arms. Multiple linear regression assessed association with 1-year change in metformin-related quantitative traits, adjusted for baseline trait, age, sex, and 10 ancestry principal compo-nents. We tested for gene-by-treatment interaction. No significant associations emerged for diabetes inci-dence. We identified four genome-wide significant variants after correcting for correlated traits (P < 9 × 1029). In the MET arm, rs144322333 near ENOSF1 (minor al-lele frequency [MAF]AFR = 0.07; MAFEUR = 0.002) was associated with an increase in percentage of glycated hemoglobin (per minor allele, b = 0.39 [95% CI 0.28, 0.50]; P = 2.8 × 10212). rs145591055 near OMSR (MAF = 0.10 in American Indians) was associated with weight loss (kilograms) (per G allele, b = 27.55 [95% CI 29.88, 25.22]; P = 3.2 × 10210) in the MET arm. Neither variant was significant in PBO; gene-by-treatment interaction was significant for both variants [P(G×T) < 1.0 × 1024 ]. Replication in individuals with diabetes did not yield significant findings. A GWAS for metformin response in prediabetes revealed novel ethnic-specific associations that require further investigation but may have implications for tailored therapy.
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| 2. |
- Marouli, Eirini, et al.
(författare)
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Rare and low-frequency coding variants alter human adult height
- 2017
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 542:7640, s. 186-190
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Tidskriftsartikel (refereegranskat)abstract
- Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.
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| 3. |
- Turcot, Valerie, et al.
(författare)
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Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity
- 2018
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 50:1, s. 26-41
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are similar to 10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed similar to 7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity.
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| 4. |
- Ameh, Soter, et al.
(författare)
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Effectiveness of an Integrated Approach to HIV and Hypertension Care in Rural South Africa : Controlled Interrupted Time-Series Analysis
- 2017
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Ingår i: Journal of Acquired Immune Deficiency Syndromes. - : LIPPINCOTT WILLIAMS & WILKINS. - 1525-4135 .- 1944-7884. ; 75:4, s. 472-479
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Tidskriftsartikel (refereegranskat)abstract
- Background: South Africa faces a dual burden of HIV/AIDS and noncommunicable diseases. In 2011, a pilot integrated chronic disease management (ICDM) model was introduced by the National Health Department into selected primary health care (PHC) facilities. The objective of this study was to assess the effectiveness of the ICDM model in controlling patients' CD4 counts (>350 cells/mm(3)) and blood pressure [BP (<140/90 mm Hg)] in PHC facilities in the Bushbuckridge municipality, South Africa. Methods: A controlled interrupted time-series study was conducted using the data from patients' clinical records collected multiple times before and after the ICDM model was initiated in PHC facilities in Bushbuckridge. Patients >18 years were recruited by proportionate sampling from the pilot (n = 435) and comparing (n = 443) PHC facilities from 2011 to 2013. Health outcomes for patients were retrieved from facility records for 30 months. We performed controlled segmented regression to model the monthly averages of individuals' propensity scores using autoregressive moving average model at 5% significance level. Results: The pilot facilities had 6% greater likelihood of controlling patients' CD4 counts than the comparison facilities (coefficient = 0.057; 95% confidence interval: 0.056 to 0.058; P < 0.001). Compared with the comparison facilities, the pilot facilities had 1.0% greater likelihood of controlling patients' BP (coefficient = 0.010; 95% confidence interval: 0.003 to 0.016; P = 0.002). Conclusions: Application of the model had a small effect in controlling patients' CD4 counts and BP, but showed no overall clinical benefit for the patients; hence, the need to more extensively leverage the HIV program for hypertension treatment.
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| 5. |
- Ameh, Soter, et al.
(författare)
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Multilevel predictors of controlled CD4 count and blood pressure in an integrated chronic disease management model in rural South Africa : a panel study
- 2020
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Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 10:11
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: In 2011, The National Department of Health introduced the Integrated Chronic Disease Management (ICDM) model as a pilot programme in selected primary healthcare facilities in South Africa. The objective of this study was to determine individual-level and facility-level predictors of controlled CD4 count and blood pressure (BP) in patients receiving treatment for HIV and hypertension, respectively.DESIGN: A panel study.SETTING AND PARTICIPANTS: This study was conducted in the Bushbuckridge Municipality, South Africa from 2011 to 2013. Facility records of patients aged ≥18 years were retrieved from the integrated chronic disease management (ICDM) pilot (n=435) and comparison facilities (n=443) using a three-step probability sampling process. CD4 count and BP control are defined as CD4 count >350 cells/mm3 and BP <140/90 mm Hg. A multilevel Least Absolute Shrinkage and Selection Operator binary logistic regression analysis was done at a 5% significance level using STATA V.16.PRIMARY OUTCOME MEASURES: CD4 (cells/mm3) count and BP (mm Hg).RESULTS: Compared with the comparison facilities, patients receiving treatment in the pilot facilities had increased odds of controlling their CD4 count (OR=5.84, 95% CI 3.21-8.22) and BP (OR=1.22, 95% CI 1.04-2.14). Patients aged 50-59 (OR=6.12, 95% CI 2.14-7.21) and ≥60 (OR=7.59, 95% CI 4.75-11.82) years had increased odds of controlling their CD4 counts compared with those aged 18-29 years. Likewise, patients aged 40-49 (OR=5.73, 95% CI 1.98-8.43), 50-59 (OR=7.28, 95% CI 4.33-9.27) and ≥60 (OR=9.31, 95% CI 5.12-13.68) years had increased odds of controlling their BP. In contrast, men had decreased odds of controlling their CD4 count (OR=0.12, 95% CI 0.10-0.46) and BP (OR=0.21, 95% CI 0.19-0.47) than women.CONCLUSION: The ICDM model had a small but significant effect on BP control, hence, the need to more effectively leverage the HIV programme for optimal BP control in the setting.
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| 6. |
- Ameh, Soter, et al.
(författare)
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Paradox of HIV stigma in an integrated chronic disease care in rural South Africa : Viewpoints of service users and providers
- 2020
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 15:7
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundAn integrated chronic disease management (ICDM) model was introduced by the National Department of Health in South Africa to tackle the dual burden of HIV/AIDS and non-communicable diseases. One of the aims of the ICDM model is to reduce HIV-related stigma. This paper describes the viewpoints of service users and providers on HIV stigma in an ICDM model in rural South Africa.Materials and methodsA content analysis of HIV stigmatisation in seven primary health care (PHC) facilities and their catchment communities was conducted in 2013 in the rural Agincourt sub-district, South Africa. Eight Focus Group Discussions were used to obtain data from 61 purposively selected participants who were 18 years and above. Seven In-Depth Interviews were conducted with the nurses-in-charge of the facilities. The transcripts were inductively analysed using MAXQDA 2018 qualitative software.ResultsThe emerging themes were HIV stigma, HIV testing and reproductive health-related concerns. Both service providers and users perceived implementation of the ICDM model may have led to reduced HIV stigma in the facilities. On the other hand, service users and providers thought HIV stigma increased in the communities because community members thought that home-based carers visited the homes of People living with HIV. Service users thought that routine HIV testing, intended for pregnant women, was linked with unwanted pregnancies among adolescents who wanted to use contraceptives but refused to take an HIV test as a precondition for receiving contraceptives.ConclusionsAlthough the ICDM model was perceived to have contributed to reducing HIV stigma in the health facilities, it was linked with stigma in the communities. This has implications for practice in the community component of the ICDM model in the study setting and elsewhere in South Africa.
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| 7. |
- Ameh, Soter, et al.
(författare)
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Predictors of health care use by adults 50 years and over in a rural South African setting
- 2014
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Ingår i: Global Health Action. - : Informa UK Limited. - 1654-9716 .- 1654-9880. ; 7, s. 1-11
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Tidskriftsartikel (refereegranskat)abstract
- Background: South Africa's epidemiological transition is characterised by an increasing burden of chronic communicable and non-communicable diseases. However, little is known about predictors of health care use (HCU) for the prevention and control of chronic diseases among older adults.Objective: To describe reported health problems and determine predictors of HCU by adults aged 50+ living in a rural sub-district of South Africa.Design: A cross-sectional study to measure HCU was conducted in 2010 in the Agincourt sub-district of Mpumalanga Province, an area underpinned by a robust health and demographic surveillance system. HCU, socio-demographic variables, reception of social grants, and type of medical aid were measured, and compared between responders who used health care services with those who did not. Predictors of HCU were determined by binary logistic regression adjusted for socio-demographic variables.Results: Seventy-five percent of the eligible adults aged 50+ responded to the survey. Average age of the targeted 7,870 older adults was 66 years (95% CI: 65.3, 65.8), and there were more women than men (70% vs. 30%, p<0.001). All 5,795 responders reported health problems, of which 96% used health care, predominantly at public health facilities (82%). Reported health problems were: chronic non-communicable diseases (41% - e. g. hypertension), acute conditions (27% - e. g. flu and fever), other conditions (26% - e. g. musculoskeletal pain), chronic communicable diseases (3% - e. g. HIV and TB), and injuries (3%). In multivariate logistic regression, responders with chronic communicable disease (OR = 5.91, 95% CI: 1.44, 24.32) and non-communicable disease (OR = 2.85, 95% CI: 1.96, 4.14) had significantly higher odds of using health care compared with those with acute conditions. Responders with six or more years of education had a two-fold increased odds of using health care (OR = 2.49, 95% CI: 1.27, 4.86) compared with those with no formal education.Conclusion: Chronic communicable and non-communicable diseases were the most prevalent and main predictors of HCU in this population, suggesting prioritisation of public health care services for chronic diseases among older people in this rural setting.
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| 8. |
- Ameh, Soter, et al.
(författare)
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Quality of integrated chronic disease care in rural South Africa : user and provider perspectives
- 2017
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Ingår i: Health Policy and Planning. - : Oxford University Press (OUP). - 0268-1080 .- 1460-2237. ; 32:2, s. 257-266
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Tidskriftsartikel (refereegranskat)abstract
- The integrated chronic disease management (ICDM) model was introduced as a response to the dual burden of HIV/AIDS and non-communicable diseases (NCDs) in South Africa, one of the first of such efforts by an African Ministry of Health. The aim of the ICDM model is to leverage HIV programme innovations to improve the quality of chronic disease care. There is a dearth of literature on the perspectives of healthcare providers and users on the quality of care in the novel ICDM model. This paper describes the viewpoints of operational managers and patients regarding quality of care in the ICDM model. In 2013, we conducted a case study of the seven PHC facilities in the rural Agincourt sub-district in northeast South Africa. Focus group discussions (n = 8) were used to obtain data from 56 purposively selected patients >= 18 years. In-depth interviews were conducted with operational managers of each facility and the sub-district health manager. Donabedian's structure, process and outcome theory for service quality evaluation underpinned the conceptual framework in this study. Qualitative data were analysed, with MAXQDA 2 software, to identify 17 a priori dimensions of care and unanticipated themes that emerged during the analysis. The manager and patient narratives showed the inadequacies in structure (malfunctioning blood pressure machines and staff shortage); process (irregular prepacking of drugs); and outcome (long waiting times). There was discordance between managers and patients regarding reasons for long patient waiting time which managers attributed to staff shortage and missed appointments, while patients ascribed it to late arrival of managers to the clinics. Patients reported anti-hypertension drug stock-outs (structure); sub-optimal defaulter-tracing (process); rigid clinic appointment system (process). Emerging themes showed that patients reported HIV stigmatisation in the community due to defaulter-tracing activities of home-based carers, while managers reported treatment of chronic diseases by traditional healers and reduced facility-related HIV stigma because HIV and NCD patients attended the same clinic. Leveraging elements of HIV programmes for NCDs, specifically hypertension management, is yet to be achieved in the study setting in part because of malfunctioning blood pressure machines and anti-hypertension drug stock-outs. This has implications for the nationwide scale up of the ICDM model in South Africa and planning of an integrated chronic disease care in other low-and middle-income countries.
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| 9. |
- Ameh, Soter, et al.
(författare)
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Relationships between structure, process and outcome to assess quality of integrated chronic disease management in a rural South African setting : applying a structural equation model
- 2017
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Ingår i: BMC Health Services Research. - : Springer Science and Business Media LLC. - 1472-6963. ; 17
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Tidskriftsartikel (refereegranskat)abstract
- Background: South Africa faces a complex dual burden of chronic communicable and non-communicable diseases (NCDs). In response, the Integrated Chronic Disease Management (ICDM) model was initiated in primary health care (PHC) facilities in 2011 to leverage the HIV/ART programme to scale-up services for NCDs, achieve optimal patient health outcomes and improve the quality of medical care. However, little is known about the quality of care in the ICDM model. The objectives of this study were to: i) assess patients’ and operational managers’ satisfaction with the dimensions of ICDM services; and ii) evaluate the quality of care in the ICDM model using Avedis Donabedian’s theory of relationships between structure (resources), process (clinical activities) and outcome (desired result of healthcare) constructs as a measure of quality of care.Methods: A cross-sectional study was conducted in 2013 in seven PHC facilities in the Bushbuckridge municipality of Mpumalanga Province, north-east South Africa - an area underpinned by a robust Health and Demographic Surveillance System (HDSS). The patient satisfaction questionnaire (PSQ-18), with measures reflecting structure/process/outcome (SPO) constructs, was adapted and administered to 435 chronic disease patients and the operational managers of all seven PHC facilities. The adapted questionnaire contained 17 dimensions of care, including eight dimensions identified as priority areas in the ICDM model - critical drugs, equipment, referral, defaulter tracing, prepacking of medicines, clinic appointments, waiting time, and coherence. A structural equation model was fit to operationalise Donabedian’s theory, using unidirectional, mediation, and reciprocal pathways.Results: The mediation pathway showed that the relationships between structure, process and outcome represented quality systems in the ICDM model. Structure correlated with process (0.40) and outcome (0.75). Given structure, process correlated with outcome (0.88). Of the 17 dimensions of care in the ICDM model, three structure (equipment, critical drugs, accessibility), three process (professionalism, friendliness and attendance to patients) and three outcome (competence, confidence and coherence) dimensions reflected their intended constructs.Conclusion: Of the priority dimensions, referrals, defaulter tracing, prepacking of medicines, appointments, and patient waiting time did not reflect their intended constructs. Donabedian’s theoretical framework can be used to provide evidence of quality systems in the ICDM model.
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| 10. |
- Arthur, Samuelina S., et al.
(författare)
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Tackling malnutrition : a systematic review of 15-year research evidence from INDEPTH health and demographic surveillance systems
- 2015
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Ingår i: Global Health Action. - : Informa UK Limited. - 1654-9716 .- 1654-9880. ; 8, s. 1-13
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Forskningsöversikt (refereegranskat)abstract
- Background: Nutrition is the intake of food in relation to the body's dietary needs. Malnutrition results from the intake of inadequate or excess food. This can lead to reduced immunity, increased susceptibility to disease, impaired physical and mental development, and reduced productivity. Objective: To perform a systematic review to assess research conducted by the International Network for the Demographic Evaluation of Populations and their Health (INDEPTH) of health and demographic surveillance systems (HDSSs) over a 15-year period on malnutrition, its determinants, the effects of under and over nutrition, and intervention research on malnutrition in low- and middle-income countries (LMICs). Methods: Relevant publication titles were uploaded onto the Zotero research tool from different databases (60% from PubMed). Using the keywords 'nutrition', 'malnutrition', 'over and under nutrition', we selected publications that were based only on data generated through the longitudinal HDSS platform. All titles and abstracts were screened to determine inclusion eligibility and full articles were independently assessed according to inclusion/exclusion criteria. For inclusion in this study, papers had to cover research on at least one of the following topics: the problem of malnutrition, its determinants, its effects, and intervention research on malnutrition. One hundred and forty eight paperswere identified and reviewed, and 67 were selected for this study. Results: The INDEPTH research identified rising levels of overweight and obesity, sometimes in the same settings as under-nutrition. Urbanisation appears to be protective against under-nutrition, but it heightens the risk of obesity. Appropriately timed breastfeeding interventions were protective against malnutrition. Conclusions: Although INDEPTH has expanded the global knowledge base on nutrition, many questions remain unresolved. There is a need for more investment in nutrition research in LMICs in order to generate evidence to inform policies in these settings.
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