| 1. |
- Kanoni, Stavroula, et al.
(författare)
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Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
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Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
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| 2. |
- Jönsson, Bengt, et al.
(författare)
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Priorities for health Economic Methodological Research: Results of an expert consultation
- 2017
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Ingår i: International Journal of Technology Assessment in Health Care. - : Cambridge University Press (CUP): HSS Journals. - 1471-6348 .- 0266-4623. ; 33:6, s. 609-619
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Tidskriftsartikel (refereegranskat)abstract
- Background: The importance of economic evaluation in decision making is growing with increasing budgetary pressures on health systems. Diverse economic evidence is available for a range of interventions across national contexts within Europe, but little attention has been given to identifying evidence gaps that, if filled, could contribute to more efficient allocation of resources. One objective of the Research Agenda for Health Economic Evaluation project is to determine the most important methodological evidence gaps for the ten highest burden conditions in the European Union (EU), and to suggest ways of filling these gaps. Methods: The highest burden conditions in the EU by Disability Adjusted Life Years were determined using the Global Burden of Disease study. Clinical interventions were identified for each condition based on published guidelines, and economic evaluations indexed in MEDLINE were mapped to each intervention. A panel of public health and health economics experts discussed the evidence during a workshop and identified evidence gaps. Results: The literature analysis contributed to identifying cross-cutting methodological and technical issues, which were considered by the expert panel to derive methodological research priorities. Conclusions: The panel suggests a research agenda for health economics which incorporates the use of real-world evidence in the assessment of new and existing interventions; increased understanding of cost-effectiveness according to patient characteristics beyond the -omics approach to inform both investment and disinvestment decisions; methods for assessment of complex interventions; improved cross-talk between economic evaluations from health and other sectors; early health technology assessment; and standardized, transferable approaches to economic modeling. © Cambridge University Press 2017.
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| 3. |
- de Graaff, Anne M., et al.
(författare)
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Scalable psychological interventions for Syrian refugees in Europe and the Middle East : STRENGTHS study protocol for a prospective individual participant data meta-analysis
- 2022
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Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 12:4
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Tidskriftsartikel (refereegranskat)abstract
- Introduction The World Health Organization's (WHO) scalable psychological interventions, such as Problem Management Plus (PM+) and Step-by-Step (SbS) are designed to be cost-effective non-specialist delivered interventions to reduce symptoms of common mental disorders, such as anxiety, depression and post-traumatic stress disorder (PTSD). The STRENGTHS consortium aims to evaluate the effectiveness, cost-effectiveness and implementation of the individual format of PM+ and its group version (gPM+), as well as of the digital SbS intervention among Syrian refugees in seven countries in Europe and the Middle East. This is a study protocol for a prospective individual participant data (IPD) meta-analysis to evaluate (1) overall effectiveness and cost-effectiveness and (2) treatment moderators of PM+, gPM+ and SbS with Syrian refugees. Methods and analysis Five pilot randomised controlled trials (RCTs) and seven fully powered RCTs conducted within STRENGTHS will be combined into one IPD meta-analytic dataset. The RCTs include Syrian refugees of 18 years and above with elevated psychological distress (Kessler Psychological Distress Scale (K10>15)) and impaired daily functioning (WHO Disability Assessment Schedule 2.0 (WHODAS 2.0>16)). Participants are randomised into the intervention or care as usual control group, and complete follow-up assessments at 1-week, 3-month and 12-month follow-up. Primary outcomes are symptoms of depression and anxiety (25-item Hopkins Symptom Checklist). Secondary outcomes include daily functioning (WHODAS 2.0), PTSD symptoms (PTSD Checklist for DSM-5) and self-identified problems (PSYCHLOPS). We will conduct a one-stage IPD meta-analysis using linear mixed models. Quality of evidence will be assessed using the GRADE approach, and the economic evaluation approach will be assessed using the CHEC-list. Ethics and dissemination Local ethical approval has been obtained for each RCT. This IPD meta-analysis does not require ethical approval. The results of this study will be published in international peer-reviewed journals.
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| 4. |
- English, Andrew, et al.
(författare)
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Genomic, Proteomic, and Phenotypic Biomarkers of COVID-19 Severity: Protocol for a Retrospective Observational Study
- 2024
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Ingår i: JMIR Research Protocols. - : JMIR PUBLICATIONS, INC. - 1929-0748. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Background: Health organizations and countries around the world have found it difficult to control the spread of COVID-19. To minimize the future impact on the UK National Health Service and improve patient care, there is a pressing need to identify individuals who are at a higher risk of being hospitalized because of severe COVID-19. Early targeted work was successful in identifying angiotensin-converting enzyme -2 receptors and type II transmembrane serine protease dependency as drivers of severe infection. Although a targeted approach highlights key pathways, a multiomics approach will provide a clearer and more comprehensive picture of severe COVID-19 etiology and progression. Objective: The COVID-19 Response Study aims to carry out an integrated multiomics analysis to identify biomarkers in blood and saliva that could contribute to host susceptibility to SARS-CoV-2 and the development of severe COVID-19. Methods: The COVID-19 Response Study aims to recruit 1000 people who recovered from SARS-CoV-2 infection in both community and hospital settings on the island of Ireland. This protocol describes the retrospective observational study component carried out in Northern Ireland (NI; Cohort A); the Republic of Ireland cohort will be described separately. For all NI participants (n=519), SARS-CoV-2 infection has been confirmed by reverse transcription -quantitative polymerase chain reaction. A prospective Cohort B of 40 patients is also being followed up at 1, 3, 6, and 12 months postinfection to assess longitudinal symptom frequency and immune response. Data will be sourced from whole blood, saliva samples, and clinical data from the electronic care records, the general health questionnaire, and a 12 -item general health questionnaire mental health survey. Saliva and blood samples were processed to extract DNA and RNA before whole-genome sequencing, RNA sequencing, DNA methylation analysis, microbiome analysis, 16S ribosomal RNA gene sequencing, and proteomic analysis were performed on the plasma. Multiomics data will be combined with clinical data to produce sensitive and specific prognostic models for severity risk. Results: An initial demographic and clinical profile of the NI Cohort A has been completed. A total of 249 hospitalized patients and 270 nonhospitalized patients were recruited, of whom 184 (64.3%) were female, and the mean age was 45.4 (SD 13) years. High levels of comorbidity were evident in the hospitalized cohort, with cardiovascular disease and metabolic and respiratory disorders being the most significant (P<.001), grouped according to the International Classification of Diseases 10 codes. Conclusions: This study will provide a comprehensive opportunity to study the mechanisms of COVID-19 severity in recontactable participants.
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| 5. |
- Jakovljevic, Mihajlo, et al.
(författare)
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Comparative financing analysis and political economy of noncommunicable diseases
- 2019
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Ingår i: Journal of Medical Economics. - : Informa UK Limited. - 1941-837X .- 1369-6998. ; 22:8, s. 722-727
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Tidskriftsartikel (refereegranskat)abstract
- The pandemic of chronic non-communicable diseases (NCDs) poses substantial challenges to the health financing sustainability in high-income and low/middle income countries (LMICs). The aim of this review is to identify the bottle neck inefficiencies in NCDs attributable spending and propose sustainable health financing solutions. The World Health Organization (WHO) introduced the "best buy" concept to scale up the core intervention package against NCDs targeted for LMICs. Population- and individual-based NCD best buy interventions are projected at US$170 billion over 2011-2025. Appropriately designed health financing arrangements can be powerful enablers to scale up the NCD best buys. Rapidly developing emerging nations dominate the landscape of LMICs. Their capability and willingness to invest resources for eradicating NCDs could strengthen WHO outreach efforts in Asia, Africa, and Latin America, much beyond current capacities. There has been a declining trend in international donor aid intended to cope with NCDs over the past decade. There is also a serious misalignment of these resources with the actual needs of recipient countries. Globally, the momentum towards the financing of intersectoral actions is growing, and this presents a cost-effective solution. A budget discrepancy of 10:1 in WHO and multilateral agencies remains in donor aid in favour of communicable diseases compared to NCDs. LMICs are likely to remain a bottleneck of NCDs imposed financing sustainability challenge in the long-run. Catastrophic household health expenditure from out of pocket spending on NCDs could plunge almost 150 million people into poverty worldwide. This epidemiological burden coupled with population ageing presents an exceptionally serious sustainability challenge, even among the richest countries which are members of the Organization for Economic Co-operation and Development (OECD). Strategic and political leadership of WHO and multilateral agencies would likely play essential roles in the struggle that has just begun.
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| 6. |
- Skokauskas, Norbert, et al.
(författare)
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The cost of child and adolescent mental health services
- 2018
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Ingår i: Lancet psychiatry. - 2215-0374 .- 2215-0366. ; 5, s. 299-300
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- More than 2·5 billion children and adolescents exist worldwide, with most individuals living in low-income and middle-income countries (LMICs).1 For these children and adolescents, mental health and neurodevelopmental disorders remain one of the leading causes of the global burden of disease and years lived with disability.2 Although the importance of child and adolescent mental health (CAMH) has been widely acknowledged by organisations such as the UN,3 the development of an inclusive cross-sectorial mental health system for children and adolescents has not gained adequate traction.
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