| 1. |
|
|
| 2. |
- de Rojas, I., et al.
(författare)
-
Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores
- 2021
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
-
Tidskriftsartikel (refereegranskat)abstract
- Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease. © 2021, The Author(s).
|
|
| 3. |
|
|
| 4. |
- Bellenguez, C, et al.
(författare)
-
New insights into the genetic etiology of Alzheimer's disease and related dementias
- 2022
-
Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 54:4, s. 412-436
-
Tidskriftsartikel (refereegranskat)abstract
- Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele.
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
- Adane, A, et al.
(författare)
-
Exploring data quality and use of the routine health information system in Ethiopia: a mixed-methods study
- 2021
-
Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 11:12, s. e050356-
-
Tidskriftsartikel (refereegranskat)abstract
- A routine health information system (RHIS) enables decision making in the healthcare system. We aimed to analyse data quality at the district and regional level and explore factors and perceptions affecting the quality and use of routine data.DesignThis was a mixed-methods study. We used the WHO toolkit for analysing data quality and interviewed staff at the point of data generation and along with the flow of data. Data were analysed using the Performance of Routine Information System Management framework.SettingThis study was performed in eight districts in four regions of Ethiopia. The study was nested within a 2-year programme of the Operational Research and Coaching for government Analysts.ParticipantsWe visited 45 health posts, 1 district hospital, 16 health centres and 8 district offices for analysis of routine RHIS data and interviewed 117 staff members for the qualitative assessment.Outcome measuresWe assessed availability of source documents, completeness, timeliness and accuracy of reporting of routine data, and explored data quality and use perceptions.ResultsThere was variable quality of both indicator and data element. Data on maternal health and immunisation were of higher quality than data on child nutrition. Issues ranged from simple organisational factors, such as availability of register books, to intricate technical issues, like complexity of indicators and choice of denominators based on population estimates. Respondents showed knowledge of the reporting procedures, but also demonstrated limited skills, lack of supportive supervision and reporting to please the next level. We saw limited examples of the use of data by the staff who were responsible for data reporting.ConclusionWe identified important organisational, technical, behavioural and process factors that need further attention to improve the quality and use of RHIS data in Ethiopia.
|
|
| 9. |
- Adane, Abyot, et al.
(författare)
-
Routine health management information system data in Ethiopia : consistency, trends, and challenges
- 2021
-
Ingår i: Global Health Action. - : Taylor & Francis. - 1654-9716 .- 1654-9880. ; 14:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Ethiopia is investing in the routine Health Management Information System. Improved routine data are needed for decision-making in the health sector.Objective: To analyse the quality of the routine Health Management Information System data and triangulate with other sources, such as the Demographic and Health Surveys.Methods: We analysed national Health Management Information System data on 19 indicators of maternal health, neonatal survival, immunization, child nutrition, malaria, and tuberculosis over the 2012-2018 time period. The analyses were conducted by 38 analysts from the Ministry of Health, Ethiopia, and two government agencies who participated in the Operational Research and Coaching for Analysts (ORCA) project between June 2018 and June 2020. Using a World Health Organization Data Quality Review toolkit, we assessed indicator definitions, completeness, internal consistency over time and between related indicators, and external consistency compared with other data sources.Results: Several services reported coverage of above 100%. For many indicators, denominators were based on poor-quality population data estimates. Data on individual vaccinations had relatively good internal consistency. In contrast, there was low external consistency for data on fully vaccinated children, with the routine Health Management Information System showing 89% coverage but the Demographic and Health Survey estimate at 39%. Maternal health indicators displayed increasing coverage over time. Indicators on child nutrition, malaria, and tuberculosis were less consistent. Data on neonatal mortality were incomplete and operationalised as mortality on day 0-6. Our comparisons with survey and population projections indicated that one in eight early neonatal deaths were reported in the routine Health Management Information System. Data quality varied between regions.Conclusions: The quality of routine data gathered in the health system needs further attention. We suggest regular triangulation with data from other sources. We recommend addressing the denominator issues, reducing the complexity of indicators, and aligning indicators to international definitions.
|
|
