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- Romagnoni, A, et al.
(author)
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Comparative performances of machine learning methods for classifying Crohn Disease patients using genome-wide genotyping data
- 2019
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In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1, s. 10351-
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Journal article (peer-reviewed)abstract
- Crohn Disease (CD) is a complex genetic disorder for which more than 140 genes have been identified using genome wide association studies (GWAS). However, the genetic architecture of the trait remains largely unknown. The recent development of machine learning (ML) approaches incited us to apply them to classify healthy and diseased people according to their genomic information. The Immunochip dataset containing 18,227 CD patients and 34,050 healthy controls enrolled and genotyped by the international Inflammatory Bowel Disease genetic consortium (IIBDGC) has been re-analyzed using a set of ML methods: penalized logistic regression (LR), gradient boosted trees (GBT) and artificial neural networks (NN). The main score used to compare the methods was the Area Under the ROC Curve (AUC) statistics. The impact of quality control (QC), imputing and coding methods on LR results showed that QC methods and imputation of missing genotypes may artificially increase the scores. At the opposite, neither the patient/control ratio nor marker preselection or coding strategies significantly affected the results. LR methods, including Lasso, Ridge and ElasticNet provided similar results with a maximum AUC of 0.80. GBT methods like XGBoost, LightGBM and CatBoost, together with dense NN with one or more hidden layers, provided similar AUC values, suggesting limited epistatic effects in the genetic architecture of the trait. ML methods detected near all the genetic variants previously identified by GWAS among the best predictors plus additional predictors with lower effects. The robustness and complementarity of the different methods are also studied. Compared to LR, non-linear models such as GBT or NN may provide robust complementary approaches to identify and classify genetic markers.
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- Cohen, O., et al.
(author)
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COST-EFFECTIVENESS ANALYSIS OF THE MINIMED (TM) 780G SYSTEM VERSUS MULTIPLE DAILY INJECTIONS WITH INTERMITTENTLY SCANNED CONTINUOUS GLUCOSE MONITORING IN INDIVIDUALS WITH TYPE 1 DIABETES IN SWEDEN
- 2021
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In: Diabetes Technology & Therapeutics. - : Mary Ann Liebert. - 1520-9156 .- 1557-8593. ; 23:Suppl. 2, s. A81-A81
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Journal article (other academic/artistic)abstract
- Background and Aims: Type 1 diabetes (T1D) therapy is continually evolving and Advanced Hybrid Closed Loop (AHCL) insulin pump systems and intermittently scanned continuous glucose monitoring (IS‐CGM) are emerging as the standard of care for many individuals with T1D. The objective of this analysis was to assess the cost‐effectiveness of the MiniMedTM 780G AHCL system versus IS‐CGM plus multiple daily injections of insulin (MDI) or continuous subcutaneous insulin infusion (CSII) in adults with T1D in Sweden.Methods: The analysis was performed using the IQVIA CORE Diabetes Model and clinical input data were sourced from observational studies. Simulated patients were assumed to have a baseline HbA1c of 7.8% (62 mmol/mol)[1] and use of the MiniMed™ 780G system was assumed to reduce HbA1c by 0.5%.[2] The analysis was performed from a societal perspective over a lifetime time horizon. Future costs and clinical outcomes were discounted at 3% per annum.Results: The MiniMedTM 780G system was associated with a quality‐adjusted life‐year (QALY) gain of 1.946 but generated higher overall costs versus MDI/CSII+IS‐CGM, leading to an incremental cost‐effectiveness ratio of SEK 373,700 (€ 36,857.80) per QALY‐gained. MiniMedTM 780G system use resulted in a lower cumulative incidence of diabetes‐related complications. Higher acquisition costs were partially offset by reduced complications costs. Extensive sensitivity analysis on key drivers confirmed the robustness of results.Conclusions: For the lifetime of adults with long‐standing T1D based in Sweden, use of the MiniMed™ 780G system is projected to be cost‐effective when compared with IS‐CGM plus MDI/CSII.
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- Franke, Andre, et al.
(author)
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Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci
- 2010
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:12, s. 1118-1125
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Journal article (peer-reviewed)abstract
- We undertook a meta-analysis of six Crohn's disease genome-wide association studies (GWAS) comprising 6,333 affected individuals (cases) and 15,056 controls and followed up the top association signals in 15,694 cases, 14,026 controls and 414 parent-offspring trios. We identified 30 new susceptibility loci meeting genome-wide significance (P < 5 × 10⁻⁸). A series of in silico analyses highlighted particular genes within these loci and, together with manual curation, implicated functionally interesting candidate genes including SMAD3, ERAP2, IL10, IL2RA, TYK2, FUT2, DNMT3A, DENND1B, BACH2 and TAGAP. Combined with previously confirmed loci, these results identify 71 distinct loci with genome-wide significant evidence for association with Crohn's disease.
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- Jansen, Willemijn J, et al.
(author)
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Prevalence Estimates of Amyloid Abnormality Across the Alzheimer Disease Clinical Spectrum.
- 2022
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In: JAMA neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 79:3, s. 228-243
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Journal article (peer-reviewed)abstract
- One characteristic histopathological event in Alzheimer disease (AD) is cerebral amyloid aggregation, which can be detected by biomarkers in cerebrospinal fluid (CSF) and on positron emission tomography (PET) scans. Prevalence estimates of amyloid pathology are important for health care planning and clinical trial design.To estimate the prevalence of amyloid abnormality in persons with normal cognition, subjective cognitive decline, mild cognitive impairment, or clinical AD dementia and to examine the potential implications of cutoff methods, biomarker modality (CSF or PET), age, sex, APOE genotype, educational level, geographical region, and dementia severity for these estimates.This cross-sectional, individual-participant pooled study included participants from 85 Amyloid Biomarker Study cohorts. Data collection was performed from January 1, 2013, to December 31, 2020. Participants had normal cognition, subjective cognitive decline, mild cognitive impairment, or clinical AD dementia. Normal cognition and subjective cognitive decline were defined by normal scores on cognitive tests, with the presence of cognitive complaints defining subjective cognitive decline. Mild cognitive impairment and clinical AD dementia were diagnosed according to published criteria.Alzheimer disease biomarkers detected on PET or in CSF.Amyloid measurements were dichotomized as normal or abnormal using cohort-provided cutoffs for CSF or PET or by visual reading for PET. Adjusted data-driven cutoffs for abnormal amyloid were calculated using gaussian mixture modeling. Prevalence of amyloid abnormality was estimated according to age, sex, cognitive status, biomarker modality, APOE carrier status, educational level, geographical location, and dementia severity using generalized estimating equations.Among the 19 097 participants (mean [SD] age, 69.1 [9.8] years; 10 148 women [53.1%]) included, 10 139 (53.1%) underwent an amyloid PET scan and 8958 (46.9%) had an amyloid CSF measurement. Using cohort-provided cutoffs, amyloid abnormality prevalences were similar to 2015 estimates for individuals without dementia and were similar across PET- and CSF-based estimates (24%; 95% CI, 21%-28%) in participants with normal cognition, 27% (95% CI, 21%-33%) in participants with subjective cognitive decline, and 51% (95% CI, 46%-56%) in participants with mild cognitive impairment, whereas for clinical AD dementia the estimates were higher for PET than CSF (87% vs 79%; mean difference, 8%; 95% CI, 0%-16%; P = .04). Gaussian mixture modeling-based cutoffs for amyloid measures on PET scans were similar to cohort-provided cutoffs and were not adjusted. Adjusted CSF cutoffs resulted in a 10% higher amyloid abnormality prevalence than PET-based estimates in persons with normal cognition (mean difference, 9%; 95% CI, 3%-15%; P = .004), subjective cognitive decline (9%; 95% CI, 3%-15%; P = .005), and mild cognitive impairment (10%; 95% CI, 3%-17%; P = .004), whereas the estimates were comparable in persons with clinical AD dementia (mean difference, 4%; 95% CI, -2% to 9%; P = .18).This study found that CSF-based estimates using adjusted data-driven cutoffs were up to 10% higher than PET-based estimates in people without dementia, whereas the results were similar among people with dementia. This finding suggests that preclinical and prodromal AD may be more prevalent than previously estimated, which has important implications for clinical trial recruitment strategies and health care planning policies.
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- Jendle, J, 1963-, et al.
(author)
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COST-EFFECTIVENESS ANALYSIS OF THE MINIMED (TM) 780G SYSTEM VERSUS MULTIPLE DAILY INJECTIONS WITH INTERMITTENTLY SCANNED CONTINUOUS GLUCOSE MONITORING IN INDIVIDUALS WITH TYPE1 DIABETES ACROSS EUROPE
- 2023
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In: Diabetes Technology & Therapeutics. - : Mary Ann Liebert. - 1520-9156 .- 1557-8593. ; 25:Suppl. 2, s. A119-A119
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Journal article (other academic/artistic)abstract
- Background and Aims: The standard of care for people with type 1 diabetes (T1D) is continually evolving and Automated Insulin Delivery system (AID) systems and continuous glucose monitoring (CGM) are emerging as the standard of care for many individuals with T1D. This study aimed to compare the long-term cost-effec-tiveness of the MiniMedTM 780G system versus MDI+ intermittently scanning CGM in people with T1D across European countries.Methods: Long-term costs and clinical outcomes were estimated using the CORE Diabetes Model. Clinical data were derived from ADAPT, prospective, multicentre, open-label, randomized control trial [1]. MiniMedTM 780G system was associated with a reduction in HbA1c of 1.54%, from 9.04% (75 mmol/mol) at baseline to 7.5% (58 mmol/mol) at the end oft he study; isCGM was associated with a reduction in HbA1c of 0.2%1. Quality of life benefits associated with a reduced fear of hypoglycaemia were also applied. Analyses were conducted in Sweden and other countries across Europe.Results: The MiniMedTM 780G system was associated with aquality-adjusted life-year (QALY) gain of 2.24 with higher overall costs versus MDI+isCGM, leading to an incremental cost-effectiveness ratio of SEK 366,919 (33,757 Euro) per QALY-gained. MiniMedTM 780G system resulted in a lower cumulative incidence of diabetes-related complications. Higher acquisition costs were partially offset by reduced complications costs. Extensive analysis of key drivers and analysis conducted across different countries confirmed the robustness of the results.Conclusions: Over patient lifetimes, for adults with T1D, the use of the AID system is projected to be cost-effective when compared with MDI+isCGM.1. Choudhary P, et al. Lancet Diabetes Endocrinol 2022 https://doi.org/10.1016/S2213-8587(22)00212-1.
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