| 1. |
- Do, Ron, et al.
(författare)
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Common variants associated with plasma triglycerides and risk for coronary artery disease
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:11, s. 1345-
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Tidskriftsartikel (refereegranskat)abstract
- Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P < 5 x 10(-8) for each) to examine the role of triglycerides in risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, and we show that the direction and magnitude of the associations with both traits are factors in determining CAD risk. Second, we consider loci with only a strong association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol (HDL-C) levels, the strength of a polymorphism's effect on triglyceride levels is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD.
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| 2. |
- Willer, Cristen J., et al.
(författare)
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Discovery and refinement of loci associated with lipid levels
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:11, s. 1274-1283
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Tidskriftsartikel (refereegranskat)abstract
- Levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and total cholesterol are heritable, modifiable risk factors for coronary artery disease. To identify new loci and refine known loci influencing these lipids, we examined 188,577 individuals using genome-wide and custom genotyping arrays. We identify and annotate 157 loci associated with lipid levels at P < 5 x 10(-8), including 62 loci not previously associated with lipid levels in humans. Using dense genotyping in individuals of European, East Asian, South Asian and African ancestry, we narrow association signals in 12 loci. We find that loci associated with blood lipid levels are often associated with cardiovascular and metabolic traits, including coronary artery disease, type 2 diabetes, blood pressure, waist-hip ratio and body mass index. Our results demonstrate the value of using genetic data from individuals of diverse ancestry and provide insights into the biological mechanisms regulating blood lipids to guide future genetic, biological and therapeutic research.
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| 3. |
- Timmerman, Stefan, et al.
(författare)
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External Validation of the Ovarian-Adnexal Reporting and Data System (O-RADS) Lexicon and the International Ovarian Tumor Analysis 2-Step Strategy to Stratify Ovarian Tumors Into O-RADS Risk Groups
- 2023
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Ingår i: JAMA Oncology. - : American Medical Association (AMA). - 2374-2437 .- 2374-2445. ; 9:2, s. 225-233
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE: Correct diagnosis of ovarian cancer results in better prognosis. Adnexal lesions can be stratified into the Ovarian-Adnexal Reporting and Data System (O-RADS) risk of malignancy categories with either the O-RADS lexicon, proposed by the American College of Radiology, or the International Ovarian Tumor Analysis (IOTA) 2-step strategy.OBJECTIVE: To investigate the diagnostic performance of the O-RADS lexicon and the IOTA 2-step strategy.DESIGN, SETTING, AND PARTICIPANTS: Retrospective external diagnostic validation study based on interim data of IOTA5, a prospective international multicenter cohort study, in 36 oncology referral centers or other types of centers. A total of 8519 consecutive adult patients presenting with an adnexal mass between January 1, 2012, and March 1, 2015, and treated either with surgery or conservatively were included in this diagnostic study. Twenty-five patients were excluded for withdrawal of consent, 2777 were excluded from 19 centers that did not meet predefined data quality criteria, and 812 were excluded because they were already in follow-up at recruitment. The analysis included 4905 patients with a newly detected adnexal mass in 17 centers that met predefined data quality criteria. Data were analyzed from January 31 to March 1, 2022.EXPOSURES: Stratification into O-RADS categories (malignancy risk <1%, 1% to <10%, 10% to <50%, and ≥50%). For the IOTA 2-step strategy, the stratification is based on the individual risk of malignancy calculated with the IOTA 2-step strategy.MAIN OUTCOMES AND MEASURES: Observed prevalence of malignancy in each O-RADS risk category, as well as sensitivity and specificity. The reference standard was the status of the tumor at inclusion, determined by histology or clinical and ultrasonographic follow-up for 1 year. Multiple imputation was used for uncertain outcomes owing to inconclusive follow-up information.RESULTS: Median age of the 4905 patients was 48 years (IQR, 36-62 years). Data on race and ethnicity were not collected. A total of 3441 tumors (70%) were benign, 978 (20%) were malignant, and 486 (10%) had uncertain classification. Using the O-RADS lexicon resulted in 1.1% (24 of 2196) observed prevalence of malignancy in O-RADS 2, 4% (34 of 857) in O-RADS 3, 27% (246 of 904) in O-RADS 4, and 78% (732 of 939) in O-RADS 5; the corresponding results for the IOTA 2-step strategy were 0.9% (18 of 1984), 4% (58 of 1304), 30% (206 of 690), and 82% (756 of 927). At the 10% risk threshold (O-RADS 4-5), the O-RADS lexicon had 92% sensitivity (95% CI, 87%-96%) and 80% specificity (95% CI, 74%-85%), and the IOTA 2-step strategy had 91% sensitivity (95% CI, 84%-95%) and 85% specificity (95% CI, 80%-88%).CONCLUSIONS AND RELEVANCE: The findings of this external diagnostic validation study suggest that both the O-RADS lexicon and the IOTA 2-step strategy can be used to stratify patients into risk groups. However, the observed malignancy rate in O-RADS 2 was not clearly below 1%.
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| 4. |
- Van Calster, Ben, et al.
(författare)
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Validation of models to diagnose ovarian cancer in patients managed surgically or conservatively : multicentre cohort study
- 2020
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Ingår i: BMJ (Clinical research ed.). - : BMJ. - 1756-1833. ; 370
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To evaluate the performance of diagnostic prediction models for ovarian malignancy in all patients with an ovarian mass managed surgically or conservatively. DESIGN: Multicentre cohort study. SETTING: 36 oncology referral centres (tertiary centres with a specific gynaecological oncology unit) or other types of centre. PARTICIPANTS: Consecutive adult patients presenting with an adnexal mass between January 2012 and March 2015 and managed by surgery or follow-up. MAIN OUTCOME MEASURES: Overall and centre specific discrimination, calibration, and clinical utility of six prediction models for ovarian malignancy (risk of malignancy index (RMI), logistic regression model 2 (LR2), simple rules, simple rules risk model (SRRisk), assessment of different neoplasias in the adnexa (ADNEX) with or without CA125). ADNEX allows the risk of malignancy to be subdivided into risks of a borderline, stage I primary, stage II-IV primary, or secondary metastatic malignancy. The outcome was based on histology if patients underwent surgery, or on results of clinical and ultrasound follow-up at 12 (±2) months. Multiple imputation was used when outcome based on follow-up was uncertain. RESULTS: The primary analysis included 17 centres that met strict quality criteria for surgical and follow-up data (5717 of all 8519 patients). 812 patients (14%) had a mass that was already in follow-up at study recruitment, therefore 4905 patients were included in the statistical analysis. The outcome was benign in 3441 (70%) patients and malignant in 978 (20%). Uncertain outcomes (486, 10%) were most often explained by limited follow-up information. The overall area under the receiver operating characteristic curve was highest for ADNEX with CA125 (0.94, 95% confidence interval 0.92 to 0.96), ADNEX without CA125 (0.94, 0.91 to 0.95) and SRRisk (0.94, 0.91 to 0.95), and lowest for RMI (0.89, 0.85 to 0.92). Calibration varied among centres for all models, however the ADNEX models and SRRisk were the best calibrated. Calibration of the estimated risks for the tumour subtypes was good for ADNEX irrespective of whether or not CA125 was included as a predictor. Overall clinical utility (net benefit) was highest for the ADNEX models and SRRisk, and lowest for RMI. For patients who received at least one follow-up scan (n=1958), overall area under the receiver operating characteristic curve ranged from 0.76 (95% confidence interval 0.66 to 0.84) for RMI to 0.89 (0.81 to 0.94) for ADNEX with CA125. CONCLUSIONS: Our study found the ADNEX models and SRRisk are the best models to distinguish between benign and malignant masses in all patients presenting with an adnexal mass, including those managed conservatively. TRIAL REGISTRATION: ClinicalTrials.gov NCT01698632.
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| 5. |
- Wynants, Laure, et al.
(författare)
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Clinical utility of risk modelsto refer patients with adnexal masses to specialized oncology care : Multicenter external validation using decision curve analysis
- 2017
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Ingår i: Clinical Cancer Research. - 1078-0432. ; 23:17, s. 5082-5090
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To evaluate the utility of preoperative diagnostic models for ovarian cancer based on ultrasound and/or biomarkers for referring patients to specialized oncology care. The investigated models were RMI, ROMA, and 3 models from the International Ovarian Tumor Analysis (IOTA) group [LR2, ADNEX, and the Simple Rules risk score (SRRisk)]. Experimental Design: A secondary analysis of prospectively collected data from 2 cross-sectional cohort studies was performed to externally validate diagnostic models. A total of 2, 763 patients (2, 403 in dataset 1 and 360 in dataset 2) from 18 centers (11 oncology centers and 7 nononcology hospitals) in 6 countries participated. Excised tissue was histologically classified as benign or malignant. The clinical utility of the preoperative diagnostic models was assessed with net benefit (NB) at a range of risk thresholds (5%-50% risk of malignancy) to refer patients to specialized oncology care. We visualized results with decision curves and generated bootstrap confidence intervals. Results: The prevalence of malignancy was 41% in dataset 1 and 40% in dataset 2. For thresholds up to 10% to 15%, RMI and ROMA had a lower NB than referring all patients. SRRisks and ADNEX demonstrated the highest NB. At a threshold of 20%, the NBs of ADNEX, SRrisks, and RMI were 0.348, 0.350, and 0.270, respectively. Results by menopausal status and type of center (oncology vs. nononcology) were similar. Conclusions: All tested IOTA methods, especially ADNEX and SRRisks, are clinically more useful than RMI and ROMA to select patients with adnexal masses for specialized oncology care.
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