| 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. |
- Jendle, Johan, 1963-, et al.
(författare)
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A European Cost-Utility Analysis of the MiniMedTM 780G Advanced Hybrid Closed-Loop System versus Intermittently Scanned Continuous Glucose Monitoring with Multiple Daily Insulin Injections in People Living with Type 1 Diabetes
- 2023
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Ingår i: Diabetes Technology & Therapeutics. - : Mary Ann Liebert. - 1520-9156 .- 1557-8593. ; 25:12, s. 864-876
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Tidskriftsartikel (refereegranskat)abstract
- Background: Advanced hybrid closed-loop (AHCL) automated insulin delivery systems are the most effective therapy in terms of assisting people with type 1 diabetes (T1D) to achieve glycemic targets; however, the cost can represent a barrier to uptake. Here, a cost-utility analysis of the MiniMedTM 780G AHCL system (MM780G) versus intermittently-scanned continuous glucose monitoring (is-CGM) plus multiple daily insulin injections (MDI) in people with T1D not achieving glycemic goals was performed across six European countries.Methods: Clinical input data were sourced from the ADAPT trial. Assuming a baseline HbA1c of 9.04%, HbA1c reductions of 1.54% for AHCL and 0.2% for is-CGM+MDI were assumed. The analyses were performed from a payer perspective over a time horizon of 40 years and an annual discount rate of 3% was applied.Results: Across all countries, the use of AHCL was projected to result in an incremental gain in quality-adjusted life expectancy of >2 quality-adjusted life years (QALYs) versus is-CGM+MDI. Lifetime direct costs were higher with AHCL resulting in incremental cost-utility ratios for AHCL versus is-CGM+MDI ranging from EUR 11,765 per QALY gained in Austria to EUR 43,963 per QALY gained in Italy.Conclusions: For people with T1D managed with is-CGM+MDI not achieving glycemic targets, initiation of the MM780G system was projected to improve long-term clinical outcomes; however, due to differences in healthcare costs between countries, the health economic outcomes differ. In the countries included here, AHCL is likely to be cost-effective relative to is-CGM+MDI for people not achieving glycemic goals with is-CGM+MDI. The ADAPT trial is registered with ClinicalTrials.gov, NCT04235504.
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| 3. |
- Jendle, Johan, 1963-, et al.
(författare)
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Cost-Effectiveness Analysis of Sensor-Augmented Insulin Pump Therapy with Automated Insulin Suspension Versus Standard Insulin Pump Therapy in Patients with Type 1 Diabetes in Sweden
- 2017
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Ingår i: Diabetes Therapy. - : Springer Berlin/Heidelberg. - 1869-6953 .- 1869-6961. ; 8:5, s. 1015-1030
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: In Sweden an estimated 10,000 people with type 1 diabetes use continuous subcutaneous insulin infusion (CSII). Sensor-augmented pump therapy (SAP) is associated with higher acquisition costs but provides additional clinical benefits (e.g. reduced rate of hypoglycemic events) over and above that of CSII alone. The aim of the analysis was to assess the cost-effectiveness of SAP with automated insulin suspension relative to CSII alone in two different groups of patients with type 1 diabetes in Sweden.Methods: Cost-effectiveness analyses were performed using the QuintilesIMS CORE Diabetes Model, with clinical and economic input data derived from published literature. Separate analyses were performed for patients at increased risk of hypoglycemia and for patients with uncontrolled glycated hemoglobin (HbA1c) at baseline. Analyses were performed from a societal perspective over a lifetime time horizon. Future costs and clinical outcomes were discounted at 3% per annum.Results: SAP with automated insulin suspension was associated with an incremental gain in quality-adjusted life expectancy versus the CSII of 1.88 quality-adjusted life years (QALYs) in patients at high risk of hypoglycemia and of 1.07 QALYs in patients with uncontrolled HbA1c at baseline. Higher lifetime costs for SAP with automated insulin suspension resulted in projected incremental cost-effectiveness ratios for the SAP with automated insulin suspension versus CSII of Swedish Krona (SEK) 139,795 [euros (EUR) 14,648] per QALY gained for patients at increased risk for hypoglycemia and SEK 251,896 (EUR 26,395) per QALY gained for patients with uncontrolled HbA1c. In both groups, SAP with automated insulin suspension also reduced the incidence of diabetes-related complications relative to CSII.Conclusions: In Sweden, SAP with automated insulin suspension likely represents a cost-effective treatment option relative to CSII for the management of patients with type 1 diabetes with a history of severe hypoglycemic events or patients who struggle to achieve good glycemic control despite the use of CSII.
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| 4. |
- Jendle, Johan, 1963-, et al.
(författare)
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Cost-Effectiveness Analysis of the MiniMed 670G Hybrid Closed-Loop System Versus Continuous Subcutaneous Insulin Infusion for Treatment of Type 1 Diabetes
- 2019
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Ingår i: Diabetes Technology & Therapeutics. - : Mary Ann Liebert. - 1520-9156 .- 1557-8593. ; 21:3, s. 110-118
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Hybrid closed-loop (HCL) systems combine continuous glucose monitoring with continuous subcutaneous insulin infusion (CSII) to continuously self-adjust basal insulin delivery. Relative to CSII, HCL improves glycemic control and reduces the risk of hypoglycemia but has higher acquisition costs. The aim of this analysis was to assess the cost-effectiveness of the MiniMed™ 670G HCL system versus CSII in people with type 1 diabetes (T1D) in Sweden.METHODS: Cost-effectiveness analysis, from a societal perspective, was performed over patient lifetimes using the IQVIA CORE Diabetes Model. Clinical data were sourced from a study comparing the MiniMed 670G system with CSII in people with T1D. Cost data, expressed in 2018 Swedish krona (SEK), were obtained from Swedish reference prices and published literature.RESULTS: The MiniMed 670G system was associated with a quality-adjusted life-year (QALY) gain of 1.90 but higher overall costs versus CSII, leading to an incremental cost-effectiveness ratio (ICER) of SEK 164,236 per QALY gained. Use of the HCL system resulted in a lower cumulative incidence of diabetes-related complications. Higher HCL system acquisition costs were partially offset by reduced complication costs and productivity losses. In people with T1D poorly controlled at baseline, the MiniMed 670G system was associated with 2.25 incremental QALYs versus CSII, yielding an ICER of SEK 15,830 per QALY gained.CONCLUSIONS: The MiniMed 670G system was associated with clinical benefits and quality-of-life improvements in people with T1D relative to CSII. At a willingness-to-pay threshold of SEK 300,000 per QALY gained, this HCL system likely represents a cost-effective treatment option for people with T1D in Sweden.
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