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1.
  • Sladkevicius, P., et al. (författare)
  • International Endometrial Tumor Analysis (IETA) terminology in women with postmenopausal bleeding and sonographic endometrial thickness ≥ 4.5 mm : agreement and reliability study
  • 2018
  • Ingår i: Ultrasound in Obstetrics and Gynecology. - : Wiley. - 0960-7692 .- 1469-0705. ; 51:2, s. 259-268
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To estimate intra- and interrater agreement and reliability with regard to describing ultrasound images of the endometrium using the International Endometrial Tumor Analysis (IETA) terminology. Methods: Four expert and four non-expert raters assessed videoclips of transvaginal ultrasound examinations of the endometrium obtained from 99 women with postmenopausal bleeding and sonographic endometrial thickness ≥ 4.5 mm but without fluid in the uterine cavity. The following features were rated: endometrial echogenicity, endometrial midline, bright edge, endometrial–myometrial junction, color score, vascular pattern, irregularly branching vessels and color splashes. The color content of the endometrial scan was estimated using a visual analog scale graded from 0 to 100. To estimate intrarater agreement and reliability, the same videoclips were assessed twice with a minimum of 2 months' interval. The raters were blinded to their own results and to those of the other raters. Results: Interrater differences in the described prevalence of most IETA variables were substantial, and some variable categories were observed rarely. Specific agreement was poor for variables with many categories. For binary variables, specific agreement was better for absence than for presence of a category. For variables with more than two outcome categories, specific agreement for expert and non-expert raters was best for not-defined endometrial midline (93% and 96%), regular endometrial–myometrial junction (72% and 70%) and three-layer endometrial pattern (67% and 56%). The grayscale ultrasound variable with the best reliability was uniform vs non-uniform echogenicity (multirater kappa (κ), 0.55 for expert and 0.52 for non-expert raters), and the variables with the lowest reliability were appearance of the endometrial–myometrial junction (κ, 0.25 and 0.16) and the nine-category endometrial echogenicity variable (κ, 0.29 and 0.28). The most reliable color Doppler variable was color score (mean weighted κ, 0.77 and 0.69). Intra- and interrater agreement and reliability were similar for experts and non-experts. Conclusions: Inter- and intrarater agreement and reliability when using IETA terminology were limited. This may have implications when assessing the association between a particular ultrasound feature and a specific histological diagnosis, because lack of reproducibility reduces the reliability of the association between a feature and the outcome. Future studies should investigate whether using fewer categories of variable or offering practical training could improve agreement and reliability.
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2.
  • Van Den Bosch, T., et al. (författare)
  • Typical ultrasound features of various endometrial pathologies described using International Endometrial Tumor Analysis (IETA) terminology in women with abnormal uterine bleeding
  • 2021
  • Ingår i: Ultrasound in Obstetrics and Gynecology. - : Wiley. - 0960-7692 .- 1469-0705. ; 57:1, s. 164-172
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To describe the ultrasound features of different endometrial and other intracavitary pathologies inpre- and postmenopausal women presenting with abnormal uterine bleeding, using the International Endometrial Tumor Analysis (IETA) terminology. Methods: This was a prospective observational multicenter study of consecutive women presenting with abnormal uterine bleeding. Unenhanced sonography with color Doppler and fluid-instillation sonography were performed. Endometrial sampling was performed according to each center's local protocol. The histological endpoints were cancer, atypical endometrial hyperplasia/endometrioid intraepithelial neoplasia (EIN), endometrial atrophy, proliferative or secretory endometrium, endometrial hyperplasia without atypia, endometrial polyp, intracavitary leiomyoma and other. For fluid-instillation sonography, the histological endpoints were endometrial polyp, intracavitary leiomyoma and cancer. For each histological endpoint, we report typical ultrasound features using the IETA terminology. Results: The database consisted of 2856 consecutive women presenting with abnormal uterine bleeding. Unenhanced sonography with color Doppler was performed in all cases and fluid-instillation sonography in 1857. In 2216 women, endometrial histology was available, and these comprised the study population. Median age was 49 years (range, 19–92 years), median parity was 2 (range, 0–10) and median body mass index was 24.9 kg/m2 (range, 16.0–72.1 kg/m2). Of the study population, 843 (38.0%) women were postmenopausal. Endometrial polyps were diagnosed in 751 (33.9%) women, intracavitary leiomyomas in 223 (10.1%) and endometrial cancer in 137 (6.2%). None (0% (95% CI, 0.0–5.5%)) of the 66 women with endometrial thickness < 3 mm had endometrial cancer or atypical hyperplasia/EIN. Endometrial cancer or atypical hyperplasia/EIN was found in three of 283 (1.1% (95% CI, 0.4–3.1%)) endometria with a three-layer pattern, in three of 459 (0.7% (95% CI, 0.2–1.9%)) endometria with a linear endometrial midline and in five of 337 (1.5% (95% CI, 0.6–3.4%)) cases with a single vessel without branching on unenhanced ultrasound. Conclusions: The typical ultrasound features of endometrial cancer, polyps, hyperplasia and atrophy and intracavitary leiomyomas, are described using the IETA terminology. The detection of some easy-to-assess IETA features (i.e. endometrial thickness < 3 mm, three-layer pattern, linear midline and single vessel without branching) makes endometrial cancer unlikely.
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3.
  • Epstein, E, et al. (författare)
  • Erratum
  • 2018
  • Ingår i: Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology. - : Wiley. - 1469-0705. ; 52:5, s. 684-684
  • Tidskriftsartikel (refereegranskat)
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5.
  • Staude, I. R., et al. (författare)
  • Directional turnover towards larger-ranged plants over time and across habitats
  • 2022
  • Ingår i: Ecology Letters. - : Wiley. - 1461-023X .- 1461-0248. ; 25:2, s. 466-82
  • Tidskriftsartikel (refereegranskat)abstract
    • Species turnover is ubiquitous. However, it remains unknown whether certain types of species are consistently gained or lost across different habitats. Here, we analysed the trajectories of 1827 plant species over time intervals of up to 78 years at 141 sites across mountain summits, forests, and lowland grasslands in Europe. We found, albeit with relatively small effect sizes, displacements of smaller- by larger-ranged species across habitats. Communities shifted in parallel towards more nutrient-demanding species, with species from nutrient-rich habitats having larger ranges. Because these species are typically strong competitors, declines of smaller-ranged species could reflect not only abiotic drivers of global change, but also biotic pressure from increased competition. The ubiquitous component of turnover based on species range size we found here may partially reconcile findings of no net loss in local diversity with global species loss, and link community-scale turnover to macroecological processes such as biotic homogenisation.
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6.
  • Eriksson, L. S.E., et al. (författare)
  • Ultrasound-based risk model for preoperative prediction of lymph-node metastases in women with endometrial cancer : model-development study
  • 2020
  • Ingår i: Ultrasound in Obstetrics and Gynecology. - : Wiley. - 0960-7692 .- 1469-0705. ; 56:3, s. 443-452
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To develop a preoperative risk model, using endometrial biopsy results and clinical and ultrasound variables, to predict the individual risk of lymph-node metastases in women with endometrial cancer. Methods: A mixed-effects logistic regression model for prediction of lymph-node metastases was developed in 1501 prospectively included women with endometrial cancer undergoing transvaginal ultrasound examination before surgery, from 16 European centers. Missing data, including missing lymph-node status, were imputed. Discrimination, calibration and clinical utility of the model were evaluated using leave-center-out cross validation. The predictive performance of the model was compared with that of risk classification from endometrial biopsy alone (high-risk defined as endometrioid cancer Grade 3/non-endometrioid cancer) or combined endometrial biopsy and ultrasound (high-risk defined as endometrioid cancer Grade 3/non-endometrioid cancer/deep myometrial invasion/cervical stromal invasion/extrauterine spread). Results: Lymphadenectomy was performed in 691 women, of whom 127 had lymph-node metastases. The model for prediction of lymph-node metastases included the predictors age, duration of abnormal bleeding, endometrial biopsy result, tumor extension and tumor size according to ultrasound and undefined tumor with an unmeasurable endometrium. The model's area under the curve was 0.73 (95% CI, 0.68–0.78), the calibration slope was 1.06 (95% CI, 0.79–1.34) and the calibration intercept was 0.06 (95% CI, –0.15 to 0.27). Using a risk threshold for lymph-node metastases of 5% compared with 20%, the model had, respectively, a sensitivity of 98% vs 48% and specificity of 11% vs 80%. The model had higher sensitivity and specificity than did classification as high-risk, according to endometrial biopsy alone (50% vs 35% and 80% vs 77%, respectively) or combined endometrial biopsy and ultrasound (80% vs 75% and 53% vs 52%, respectively). The model's clinical utility was higher than that of endometrial biopsy alone or combined endometrial biopsy and ultrasound at any given risk threshold. Conclusions: Based on endometrial biopsy results and clinical and ultrasound characteristics, the individual risk of lymph-node metastases in women with endometrial cancer can be estimated reliably before surgery. The model is superior to risk classification by endometrial biopsy alone or in combination with ultrasound.
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  • Lakens, Daniel, et al. (författare)
  • Justify your alpha
  • 2018
  • Ingår i: Nature Human Behaviour. - : Nature Publishing Group. - 2397-3374. ; 2:3, s. 168-171
  • Tidskriftsartikel (refereegranskat)abstract
    • In response to recommendations to redefine statistical significance to P ≤ 0.005, we propose that researchers should transparently report and justify all choices they make when designing a study, including the alpha level.
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9.
  • Timmerman, D., et al. (författare)
  • Ovarian cancer prediction in adnexal masses using ultrasound-based logistic regression models: a temporal and external validation study by the IOTA group
  • 2010
  • Ingår i: Ultrasound in Obstetrics & Gynecology. - : Wiley. - 1469-0705 .- 0960-7692. ; 36:2, s. 226-234
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives The aims of the study were to temporally and externally validate the diagnostic performance of two logistic regression models containing clinical and ultrasound variables in order to estimate the risk of malignancy in adnexal masses, and to compare the results with the subjective interpretation of ultrasound findings carried out by an experienced ultrasound examiner ('subjective assessment'). Methods Patients with adnexal masses, who were put forward by the 19 centers participating in the study, underwent a standardized transvaginal ultrasound examination by a gynecologist or a radiologist specialized in ultrasonography. The examiner prospectively collected information on clinical and ultrasound variables, and classified each mass as benign or malignant on the basis of subjective evaluation of ultrasound findings. The gold standard was the histology of the mass with local clinicians deciding whether to operate on the basis of ultrasound results and the clinical picture. The models' ability to discriminate between malignant and benign masses was assessed, together with the accuracy of the risk estimates. Results Of the 1938 patients included in the study, 1396 had benign, 373 had primary invasive, 111 had borderline malignant and 58 had metastatic tumors. On external validation (997 patients from 12 centers), the area under the receiver operating characteristics curve (AUC) for a model containing 12 predictors (LR1) was 0.956, for a reduced model with six predictors (LR2) was 0.949 and for subjective assessment was 0.949. Subjective assessment gave a positive likelihood ratio of 11.0 and a negative likelihood ratio of 0.14. The corresponding likelihood ratios for a previously derived probability threshold (0.1) were 6.84 and 0.09 for LR1, and 6.36 and 0.10 for LR2. On temporal validation (941 patients from seven centers), the AUCs were 0.945 (LR1), 0.918 (LR2) and 0.959 (subjective assessment). Conclusions Both models provide excellent discrimination between benign and malignant masses. Because the models provide an objective and reasonably accurate risk estimation, they may improve the management of women with suspected ovarian pathology. Copyright (C) 2010 ISUOG. Published by John Wiley & Sons, Ltd.
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10.
  • Timmerman, D., et al. (författare)
  • Simple ultrasound-based rules for the diagnosis of ovarian cancer
  • 2008
  • Ingår i: Ultrasound in Obstetrics & Gynecology. - : Wiley. - 1469-0705 .- 0960-7692. ; 31:6, s. 681-690
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective To derive simple and clinically useful ultrasound-based rules for discriminating between benign and malignant adnexal masses. Methods In a multicenter study involving nine centers consecutive patients with persistent adnexal tumors underwent transvaginal gray-scale and Doppler ultrasound examination using a standardized examination technique and standardized terms and definitions. Information on 42 gray-scale ultrasound variables and six Doppler variables was collected and entered into a research protocol. When developing simple ultrasound-based rules to predict malignancy (M-rules) we chose the ultrasound variable or the combination of ultrasound variables that bad the highest positive predictive value (PPV) with regard to malignancy; when developing simple rules to predict a benign tumor (B-rules) we chose the ultrasound variable or the combination of ultrasound variables that had the lowest PPV with regard to malignancy. We selected ten rules that were in agreement with our clinical experience and were applicable to at least 30 tumors and then tested them prospectively on 507 tumors examined in three of the nine centers. Results 1066 patients with 1233 adnexal tumors were included. There were 903 benign tumors (73%) and 330 malignant tumors (27%). In 167 patients the tumors were bilateral. We selected five simple rules to predict malignancy (M-rules): (1) irregular solid tumor; (2) ascites; (3) at least four papillary structures; (4) irregular multilocular-solid tumor with a largest diameter of at least 100 mm; and (5) very high color content on color Doppler examination. We chose five simple rules to suggest a benign tumor (B-rules): (1) unilocular cyst; (2) presence of solid components where the largest solid component is < 7 mm in largest diameter; (3) acoustic shadows; (4) smooth multilocular tumor less than 100 mm in largest diameter; and (S) no detectable blood flow on Doppler examination. These ten rules were applicable to 76% of all tumors, where they resulted in a sensitivity of 93%, specificity of 90%, positive likelihood ratio (LR+) of 9.45 and negative likelihood ratio (LR-) of 0.08. When prospectively tested the rules were applicable in 76% (386/507) of the tumors, where they had a sensitivity of 95% (106/112), a specificity of 91% (249/274), LR+ of 10.37, and LR- of 0.06. Conclusion Most adnexal tumors in an ordinary tumor population can be correctly classified as benign or malignant using simple ultrasound-based rules. For tumors that cannot be classified using simple rules, ultrasound examination by an expert examiner might be useful. Copyright (C) 2008 ISUOG. Published by John Wiley & Sons, Ltd.
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11.
  • Valentin, Lil, et al. (författare)
  • Adding a single CA 125 measurement to ultrasound imaging performed by an experienced examiner does not improve preoperative discrimination between benign and malignant adnexal masses.
  • 2009
  • Ingår i: Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology. - : Wiley. - 1469-0705. ; 34, s. 345-354
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: To determine whether CA 125 measurement is superior to ultrasound imaging performed by an experienced examiner for discriminating between benign and malignant adnexal lesions, and to determine whether adding CA 125 to ultrasound examination improves diagnostic performance. METHODS: This is a prospective multicenter study (International Ovarian Tumor Analysis (IOTA) study) conducted in nine European ultrasound centers in university hospitals. Of 1149 patients with an adnexal mass examined in the IOTA study, 83 were excluded. Of the remaining 1066 patients, 809 had CA 125 results available and were included. The patients underwent preoperative serum CA 125 measurements and transvaginal ultrasound examination by an experienced ultrasound examiner blinded to CA 125 values. The examiner classified each mass as certainly or probably benign, difficult to classify, or probably or certainly malignant. The outcome measure was the sensitivity and specificity with regard to malignancy of CA 125, ultrasound imaging and their combined use, the 'gold standard' being the histological diagnosis of the adnexal mass removed surgically within 120 days after the ultrasound examination. RESULTS: There were 242 (30%) malignancies. For 534 tumors judged to be certainly benign or certainly malignant by the ultrasound examiner the sensitivity and specificity of ultrasound examination and CA 125 (>/=35 U/mL indicating malignancy) were 97% vs. 86% (95% CI of difference, 4.7-17.2) and 99% vs. 79% (95% CI of difference, 15.7-24.2); for 209 tumors judged probably benign or probably malignant, sensitivity and specificity were 81% vs. 57% (95% CI of difference, 12.3-36.0) and 91% vs. 74% (95% CI of difference, 8.5-25.7); for 66 tumors that were difficult to classify, sensitivity and specificity were 57% vs. 39% (95% CI of difference, -9.7 to 41.1) and 74% vs. 67% (95% CI of difference, -14.6 to 27.7). Diagnostic performance deteriorated when CA 125 was used as a second-stage test after ultrasound examination. CONCLUSIONS: Specialist ultrasound examination is superior to CA 125 for preoperative discrimination between benign and malignant adnexal masses, irrespective of the diagnostic confidence of the ultrasound examiner; adding CA 125 to ultrasound does not improve diagnostic performance. Our results indicate that greater investment in education and training in gynecological ultrasound imaging would be of value. Copyright (c) 2009 ISUOG. Published by John Wiley & Sons, Ltd.
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13.
  • Van Calster, B, et al. (författare)
  • Classifying ovarian tumors using Bayesian Multi-Layer Perceptrons and Automatic Relevance Determination: A multi-center study
  • 2006
  • Ingår i: Engineering in Medicine and Biology Society, 2006. EMBS '06. 28th Annual International Conference of the IEEE. - 1557-170X. ; 1, s. 5342-5345
  • Konferensbidrag (refereegranskat)abstract
    • Ovarian masses are common and a good pre-surgical assessment of their nature is important for adequate treatment. Bayesian Multi-Layer Perceptrons (MLPs) using the evidence procedure were used to predict whether tumors are malignant or not. Automatic Relevance Determination (ARD) is used to select the most relevant of the 40+ available variables. Cross-validation is used to select an optimal combination of input set and number of hidden neurons. The data set consists of 1066 tumors collected at nine centers across Europe. Results indicate good performance of the models with AUC values of 0.93-0.94 on independent data. A comparison with a Bayesian perceptron model shows that the present problem is to a large extent linearly separable. The analyses further show that the number of hidden neurons specified in the ARD analyses for input selection may influence model performance.
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  • Van Calster, B., et al. (författare)
  • Preoperative diagnosis of ovarian tumors using Bayesian kernel-based methods
  • 2007
  • Ingår i: Ultrasound in Obstetrics & Gynecology. - : Wiley. - 1469-0705 .- 0960-7692. ; 29:5, s. 496-504
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives To develop flexible classifiers that predict malignancy in adnexal masses using a large database from nine centers. Methods The database consisted of 1066 patients with at least one persistent adnexal mass for which a large amount of clinical and ultrasound data were recorded. The outcome of interest was the histological classification of the adnexal mass as benign or malignant. The outcome was predicted using Bayesian least squares support vector machines in comparison with relevance vector machines. The models were developed on a training set (n = 754) and tested on a test set (n = 312). Results Twenty-five percent of the patients (n = 266) bad a malignant tumor. Variable selection resulted in a set of 12 variables for the models: age, maximal diameter of the ovary, maximal diameter of the solid component, personal history of ovarian cancer, hormonal therapy, very strong intratumoral blood flow (i.e. color score 4), ascites, presumed ovarian origin of tumor, multilocular-solid tumor, blood flow within papillary projections, irregular internal cyst wall and acoustic shadows. Test set area under the receiver-operating characteristics curve (AUC) for all models exceeded 0.940, with a sensitivity above 90% and a specificity above 80% for all models. The least squares support vector machine model with linear kernel performed very well, with an AUC of 0.946, 91% sensitivity and 84% specificity. The models performed well in the test sets of all the centers. Conclusions Bayesian kernel-based methods can accurately separate malignant from benign masses. The robustness of the models will be investigated in future studies. Copyright (c) 2007 ISUOG. Published by John Wiley & Sons, Ltd.
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17.
  • De Jong, VMT, et al. (författare)
  • Clinical prediction models for mortality in patients with covid-19: external validation and individual participant data meta-analysis
  • 2022
  • Ingår i: BMJ (Clinical research ed.). - : BMJ. - 1756-1833. ; 378, s. e069881-
  • Tidskriftsartikel (refereegranskat)abstract
    • ObjectiveTo externally validate various prognostic models and scoring rules for predicting short term mortality in patients admitted to hospital for covid-19.DesignTwo stage individual participant data meta-analysis.SettingSecondary and tertiary care.Participants46 914 patients across 18 countries, admitted to a hospital with polymerase chain reaction confirmed covid-19 from November 2019 to April 2021.Data sourcesMultiple (clustered) cohorts in Brazil, Belgium, China, Czech Republic, Egypt, France, Iran, Israel, Italy, Mexico, Netherlands, Portugal, Russia, Saudi Arabia, Spain, Sweden, United Kingdom, and United States previously identified by a living systematic review of covid-19 prediction models published inThe BMJ, and through PROSPERO, reference checking, and expert knowledge.Model selection and eligibility criteriaPrognostic models identified by the living systematic review and through contacting experts. A priori models were excluded that had a high risk of bias in the participant domain of PROBAST (prediction model study risk of bias assessment tool) or for which the applicability was deemed poor.MethodsEight prognostic models with diverse predictors were identified and validated. A two stage individual participant data meta-analysis was performed of the estimated model concordance (C) statistic, calibration slope, calibration-in-the-large, and observed to expected ratio (O:E) across the included clusters.Main outcome measures30 day mortality or in-hospital mortality.ResultsDatasets included 27 clusters from 18 different countries and contained data on 46 914patients. The pooled estimates ranged from 0.67 to 0.80 (C statistic), 0.22 to 1.22 (calibration slope), and 0.18 to 2.59 (O:E ratio) and were prone to substantial between study heterogeneity. The 4C Mortality Score by Knight et al (pooled C statistic 0.80, 95% confidence interval 0.75 to 0.84, 95% prediction interval 0.72 to 0.86) and clinical model by Wang et al (0.77, 0.73 to 0.80, 0.63 to 0.87) had the highest discriminative ability. On average, 29% fewer deaths were observed than predicted by the 4C Mortality Score (pooled O:E 0.71, 95% confidence interval 0.45 to 1.11, 95% prediction interval 0.21 to 2.39), 35% fewer than predicted by the Wang clinical model (0.65, 0.52 to 0.82, 0.23 to 1.89), and 4% fewer than predicted by Xie et al’s model (0.96, 0.59 to 1.55, 0.21 to 4.28).ConclusionThe prognostic value of the included models varied greatly between the data sources. Although the Knight 4C Mortality Score and Wang clinical model appeared most promising, recalibration (intercept and slope updates) is needed before implementation in routine care.
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  • Di Legge, A., et al. (författare)
  • Lesion size affects diagnostic performance of IOTA logistic regression models, IOTA simple rules and risk of malignancy index in discriminating between benign and malignant adnexal masses
  • 2012
  • Ingår i: Ultrasound in Obstetrics & Gynecology. - : Wiley. - 1469-0705 .- 0960-7692. ; 40:3, s. 345-354
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives To estimate the ability to discriminate between benign and malignant adnexal masses of different size using: subjective assessment, two International Ovarian Tumor Analysis (IOTA) logistic regression models (LR1 and LR2), the IOTA simple rules and the risk of malignancy index (RMI). Methods We used a multicenter IOTA database of 2445 patients with at least one adnexal mass, i.e. the database previously used to prospectively validate the diagnostic performance of LR1 and LR2. The masses were categorized into three subgroups according to their largest diameter: small tumors (diameter < 4 cm; n = 396), medium-sized tumors (diameter, 49.9 cm; n = 1457) and large tumors (diameter = 10 cm, n = 592). Subjective assessment, LR1 and LR2, IOTA simple rules and the RMI were applied to each of the three groups. Sensitivity, specificity, positive and negative likelihood ratio (LR+, LR-), diagnostic odds ratio (DOR) and area under the receiveroperating characteristics curve (AUC) were used to describe diagnostic performance. A moving window technique was applied to estimate the effect of tumor size as a continuous variable on the AUC. The reference standard was the histological diagnosis of the surgically removed adnexal mass. Results The frequency of invasive malignancy was 10% in small tumors, 19% in medium-sized tumors and 40% in large tumors; 11% of the large tumors were borderline tumors vs 3% and 4%, respectively, of the small and medium-sized tumors. The type of benign histology also differed among the three subgroups. For all methods, sensitivity with regard to malignancy was lowest in small tumors (5684% vs 6793% in medium-sized tumors and 7495% in large tumors) while specificity was lowest in large tumors (6087%vs 8395% in medium-sized tumors and 8396% in small tumors ). The DOR and the AUC value were highest in medium-sized tumors and the AUC was largest in tumors with a largest diameter of 711 cm. Conclusion Tumor size affects the performance of subjective assessment, LR1 and LR2, the IOTA simple rules and the RMI in discriminating correctly between benign and malignant adnexal masses. The likely explanation, at least in part, is the difference in histology among tumors of different size. Copyright (C) 2012 ISUOG. Published by John Wiley & Sons, Ltd.
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19.
  • Kaijser, J., et al. (författare)
  • Improving strategies for diagnosing ovarian cancer: a summary of the International Ovarian Tumor Analysis (IOTA) studies
  • 2013
  • Ingår i: Ultrasound in Obstetrics & Gynecology. - : Wiley. - 1469-0705 .- 0960-7692. ; 41:1, s. 9-20
  • Forskningsöversikt (refereegranskat)abstract
    • In order to ensure that ovarian cancer patients access appropriate treatment to improve the outcome of this disease, accurate characterization before any surgery on ovarian pathology is essential. The International Ovarian Tumor Analysis (IOTA) collaboration has standardized the approach to the ultrasound description of adnexal pathology. A prospectively collected large database enabled previously developed prediction models like the risk of malignancy index (RMI) to be tested and novel prediction models to be developed and externally validated in order to determine the optimal approach to characterize adnexal pathology preoperatively. The main IOTA prediction models (logistic regression model 1 (LR1) and logistic regression model 2 (LR2)) have both shown excellent diagnostic performance (area under the curve (AUC) values of 0.96 and 0.95, respectively) and outperform previous diagnostic algorithms. Their test performance almost matches subjective assessment by experienced examiners, which is accepted to be the best way to classify adnexal masses before surgery. A two-step strategy using the IOTA simple rules supplemented with subjective assessment of ultrasound findings when the rules do not apply, also reached excellent diagnostic performance (sensitivity 90%, specificity 93%) and misclassified fewer malignancies than did the RMI. An evidence-based approach to the preoperative characterization of ovarian and other adnexal masses should include the use of LR1, LR2 or IOTA simple rules and subjective assessment by an experienced examiner. Copyright (c) 2012 ISUOG. Published by John Wiley & Sons, Ltd.
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20.
  • Landolfo, C., et al. (författare)
  • Benign descriptors and ADNEX in two-step strategy to estimate risk of malignancy in ovarian tumors : retrospective validation on IOTA 5 multicenter cohort
  • 2023
  • Ingår i: Ultrasound in Obstetrics and Gynecology. - : Wiley. - 0960-7692 .- 1469-0705. ; 61:2, s. 231-242
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Previous work suggested that the ultrasound-based benign Simple Descriptors can reliably exclude malignancy in a large proportion of women presenting with an adnexal mass. We aim to validate a modified version of the Benign Simple Descriptors (BD), and we introduce a two-step strategy to estimate the risk of malignancy: if the BDs do not apply, the ADNEX model is used to estimate the risk of malignancy. Methods: This is a retrospective analysis using the data from the 2-year interim analysis of the IOTA5 study, in which consecutive patients with at least one adnexal mass were recruited irrespective of subsequent management (conservative or surgery). The main outcome was classification of tumors as benign or malignant, based on histology or on clinical and ultrasound information during one year of follow-up. Multiple imputation was used when outcome based on follow-up was uncertain according to predefined criteria. Results: 8519 patients were recruited at 36 centers between 2012 and 2015. We included all masses that were not already in follow-up at recruitment from 17 centers with good quality surgical and follow-up data, leaving 4905 patients for statistical analysis. 3441 (70%) tumors were benign, 978 (20%) malignant, and 486 (10%) uncertain. The BDs were applicable in 1798/4905 (37%) tumors, and 1786 (99.3%) of these were benign. The two-step strategy based on ADNEX without CA125 had an area under the receiver operating characteristic curve (AUC) of 0.94 (95% CI, 0.91-0.95). The risk of malignancy was slightly underestimated, but calibration varied between centers. A sensitivity analysis in which we expanded the definition of uncertain outcome resulted in 1419 (29%) tumors with uncertain outcome and an AUC of the two-step strategy without CA125 of 0.93 (95% CI, 0.91-0.95). Conclusion: A large proportion of adnexal masses can be classified as benign by the BDs. For the remaining masses the ADNEX model can be used to estimate the risk of malignancy. This two-step strategy is convenient for clinical use.
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21.
  • Staude, I. R., et al. (författare)
  • Replacements of small- by large-ranged species scale up to diversity loss in Europe's temperate forest biome
  • 2020
  • Ingår i: Nature Ecology & Evolution. - : Springer Science and Business Media LLC. - 2397-334X. ; 4, s. 802-808
  • Tidskriftsartikel (refereegranskat)abstract
    • The loss of biodiversity at the global scale has been difficult to reconcile with observations of no net loss at local scales. Vegetation surveys across European temperate forests show that this may be explained by the replacement of small-ranged species with large-ranged ones, driven by nitrogen deposition. Biodiversity time series reveal global losses and accelerated redistributions of species, but no net loss in local species richness. To better understand how these patterns are linked, we quantify how individual species trajectories scale up to diversity changes using data from 68 vegetation resurvey studies of seminatural forests in Europe. Herb-layer species with small geographic ranges are being replaced by more widely distributed species, and our results suggest that this is due less to species abundances than to species nitrogen niches. Nitrogen deposition accelerates the extinctions of small-ranged, nitrogen-efficient plants and colonization by broadly distributed, nitrogen-demanding plants (including non-natives). Despite no net change in species richness at the spatial scale of a study site, the losses of small-ranged species reduce biome-scale (gamma) diversity. These results provide one mechanism to explain the directional replacement of small-ranged species within sites and thus explain patterns of biodiversity change across spatial scales.
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22.
  • Testa, A, et al. (författare)
  • Strategies to diagnose ovarian cancer: new evidence from phase 3 of the multicentre international IOTA study.
  • 2014
  • Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 1532-1827 .- 0007-0920. ; 111:4, s. 680-688
  • Tidskriftsartikel (refereegranskat)abstract
    • Background:To compare different ultrasound-based international ovarian tumour analysis (IOTA) strategies and risk of malignancy index (RMI) for ovarian cancer diagnosis using a meta-analysis approach of centre-specific data from IOTA3.Methods:This prospective multicentre diagnostic accuracy study included 2403 patients with 1423 benign and 980 malignant adnexal masses from 2009 until 2012. All patients underwent standardised transvaginal ultrasonography. Test performance of RMI, subjective assessment (SA) of ultrasound findings, two IOTA risk models (LR1 and LR2), and strategies involving combinations of IOTA simple rules (SRs), simple descriptors (SDs) and LR2 with and without SA was estimated using a meta-analysis approach. Reference standard was histology after surgery.Results:The areas under the receiver operator characteristic curves of LR1, LR2, SA and RMI were 0.930 (0.917-0.942), 0.918 (0.905-0.930), 0.914 (0.886-0.936) and 0.875 (0.853-0.894). Diagnostic one-step and two-step strategies using LR1, LR2, SR and SD achieved summary estimates for sensitivity 90-96%, specificity 74-79% and diagnostic odds ratio (DOR) 32.8-50.5. Adding SA when IOTA methods yielded equivocal results improved performance (DOR 57.6-75.7). Risk of Malignancy Index had sensitivity 67%, specificity 91% and DOR 17.5.Conclusions:This study shows all IOTA strategies had excellent diagnostic performance in comparison with RMI. The IOTA strategy chosen may be determined by clinical preference.British Journal of Cancer advance online publication 17 June 2014; doi:10.1038/bjc.2014.333 www.bjcancer.com.
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23.
  • Timmerman, D, et al. (författare)
  • Logistic regression model to distinguish between the benign and malignant adnexal mass before surgery: A multicenter study by the International Ovarian Tumor Analysis Group
  • 2005
  • Ingår i: Journal of Clinical Oncology. - 1527-7755. ; 23:34, s. 8794-8801
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose To collect data for the development of a more universally useful logistic regression model to distinguish between a malignant and benign adnexal tumor before surgery. Patients and Methods Patients had at least one persistent mass. More than 50 clinical and sonographic end points were defined and recorded for analysis. The outcome measure was the histologic classification of excised tissues as malignant or benign. Results Data from 1,066 patients recruited from nine European centers were included in the analysis; 800 patients (75%) had benign tumors and 266 (25%) had malignant tumors. The most useful independent prognostic variables for the logistic regression model were as follows: (1) personal history of ovarian cancer, (2) hormonal therapy, (3) age, (4) maximum diameter of lesion, (5) pain, (6) ascites, (7) blood flow within a solid papillary projection, (8) presence of an entirely solid tumor, (9) maximal diameter of solid component, (10) irregular internal cyst walls, (11) acoustic shadows, and (12) a color score of intratumoral blood flow. The model containing all 12 variables (M1) gave an area under the receiver operating characteristic curve of 0.95 for the development data set (n = 754 patients). The corresponding value for the test data set (n = 312 patients) was 0.94; and a probability cutoff value of .10 gave a sensitivity of 93% and a specificity of 76%. Conclusion Because the model was constructed from multicenter data, it is more likely to be generally applicable. The effectiveness of the model will be tested prospectively at different centers.
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24.
  • Van Holsbeke, C., et al. (författare)
  • Endometriomas: their ultrasound characteristics
  • 2010
  • Ingår i: Ultrasound in Obstetrics & Gynecology. - : Wiley. - 1469-0705 .- 0960-7692. ; 35:6, s. 730-740
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives To describe the ultrasound characteristics of endometriomas in pre- and postmenopausal patients and to develop rules that characterize endometriomas. Methods All patients included in the International Ovarian Tumor Analysis (IOTA) studies were used in our analysis. Patients with an adnexal mass were scanned by experienced sonologists using a standardized research protocol. The gold standard was the histology of the surgically removed adnexal mass. The gray-scale and Doppler ultrasound characteristics of the endometriomas were compared with those of other benign and malignant masses. Based on decision-tree analysis, the existing literature and clinical experience, ultrasound rules for the detection of endometriomas were created and evaluated. Results Of all 3511 patients included in the IOTA studies, 713 (20%) had endometriomas. Fifty-one per cent of the endometriomas were unilocular cysts with ground glass echogenicity of the cyst fluid. These characteristics were found less often among other benign tumors or malignancies, or among the small set of endometriomas (4%) that were found in postmenopausal patients. Based on the decision-tree analysis, the optimal rule to detect endometriomas was an adnexal mass in a premenopausal patient with ground glass echogenicity of the cyst fluid, one to four locules and no papillations with detectable blood flow'. Based on clinical considerations, the following rule: 'premenopausal status, ground glass echogenicity of the cyst fluid, one to four locules and no solid parts' seems preferable. Conclusions Several rules had a good ability to characterize endometriomas. The ultrasound characteristics of endometriomas differ between pre- and postmenopausal patients. Masses in postmenopausal women whose cystic contents have a ground glass appearance have a high risk of malignancy. Copyright (C) 2010 ISUOG. Published by John Wiley & Sons, Ltd.
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25.
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26.
  • Reinecke, J., et al. (författare)
  • Acido- and neutrophilic temperate forest plants display distinct shifts in ecological pH niche across north-western Europe
  • 2016
  • Ingår i: Ecography. - : Wiley. - 0906-7590 .- 1600-0587. ; 39:12, s. 1164-1175
  • Tidskriftsartikel (refereegranskat)abstract
    • Ecological niches of organisms vary across geographical space, but niche shift patterns between regions and the underlying mechanisms remain largely unexplored. We studied shifts in the pH niche of 42 temperate forest plant species across a latitudinal gradient from northern France to boreo-nemoral Sweden. We asked 1) whether species restrict their niches with increasing latitude as they reach their northern range margin (environmental constraints); 2) whether species expand their niches with increasing latitude as regional plant species richness decreases (competitive release); and 3) whether species shift their niche position toward more acidic sites with increasing latitude as the relative proportion of acidic soils increases (local adaptation). Based on 1458 vegetation plots and corresponding soil pH values, we modelled species response curves using Huisman-Olff-Fresco models. Four niche measures (width, position, left and right border) were compared among regions by randomization tests. We found that with increasing latitude, neutrophilic species tended to retreat from acidic sites, indicating that these species retreat to more favorable sites when approaching their range margin. Alternatively, these species might benefit from enhanced nitrogen deposition on formerly nutrient-poor, acidic sites in southern regions or lag behind in post-glacial recolonization of potential habitats in northern regions. Most acidophilic species extended their niche toward more base-rich sites with increasing latitude, indicating competitive release from neutrophilic species. Alternatively, acidophilic species might benefit from optimal climatic conditions in the north where some have their core distribution area. Shifts in the niche position suggested that local adaptation is of minor importance. We conclude that shifts in the pH niche of temperate forest plants are the rule, but the directions of the niche shifts and possible explanations vary. Our study demonstrates that differentiating between acidophilic and neutrophilic species is crucial to identify general patterns and underlying mechanisms.
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27.
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28.
  • Van Calster, B, et al. (författare)
  • Triaging women with ovarian masses for surgery: observational diagnostic study to compare RCOG guidelines with an International Ovarian Tumour Analysis (IOTA) group protocol.
  • 2012
  • Ingår i: BJOG: An International Journal of Obstetrics & Gynaecology. - : Wiley. - 1471-0528 .- 1470-0328.
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To compare guidelines from the Royal College of Obstetricians and Gynaecologists (RCOG) based on the Risk of Malignancy Index (RMI) with a protocol based on logistic regression model LR2 developed by the International Ovarian Tumour Analysis (IOTA) group for triaging women with an ovarian mass as low, moderate, or high risk of malignancy. Design and setting Observational diagnostic study conducted between 2005 and 2007 at 21 oncology referral centres, referral centres for ultrasonography and general hospitals. Sample In all, 1938 women undergoing surgery for an ovarian mass. Methods: RCOG guidelines use the RMI to triage women as low (RMI < 25), moderate (25-250), or high (above >250) risk. The IOTA protocol uses LR2s estimated probability of malignancy (<0.05 indicates low risk, ≥0.05 but <0.25 moderate risk, and ≥0.25 high risk). Main outcome measure Percentages of benign, borderline and invasive tumours classified as low, moderate or high risk. Results: The IOTA and RCOG protocols classified 71.1% and 62.1% of benign tumours as low risk, respectively (difference 9.0; 95% CI 6.2-11.9, P < 0.0001). Of invasive tumours, 88.6% and 73.6% were labelled high risk (difference 15.0; 10.6-19.4, P < 0.0001), and 3.0% and 5.2% were labelled low risk (difference -2.2; -4.6 to 0.2, P = 0.07) respectively by each protocol. Similar results were found after stratification for menopausal status. Conclusions: The IOTA protocol was more accurate for triage than the RCOG protocol. The IOTA protocol would avoid major surgery for more women with benign tumours while still appropriately referring more women with an invasive tumour to a gynaecological oncologist.
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