A methodology for point-in-time–through-the-cycle probability of default decomposition in risk classification systems

2012 ◽  
Vol 6 (3) ◽  
pp. 3-25 ◽  
Author(s):  
Magnus Carlehed ◽  
Alexander Petrov
Keyword(s):  
Risk Classification ◽  
Classification Systems ◽  
Probability Of Default

scholarly journals BRAF V600E Status and Stimulated Thyroglobulin at Ablation Time Increase Prognostic Value of American Thyroid Association Classification Systems for Persistent Disease in Differentiated Thyroid Carcinoma

2019 ◽  
Vol 2019 ◽  
pp. 1-7
Author(s):  
Andrea Repaci ◽  
Valentina Vicennati ◽  
Alexandro Paccapelo ◽  
Ottavio Cavicchi ◽  
Nicola Salituro ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Risk Stratification ◽  
Prognostic Value ◽  
Differentiated Thyroid Cancer ◽  
Risk Classification ◽  
Classification Systems ◽  
Braf V600e ◽  
American Thyroid Association ◽  
Persistent Disease ◽  
Ablation Time

Background. Stimulated thyroglobulin levels measured at the time of remnant ablation (A-hTg) and BRAFV600E mutation had shown prognostic value in predicting persistent disease in differentiated thyroid cancer (DTC). The aim of this study was to evaluate the prognostic role of A-hTg combined with the BRAFV600E status in association with the revised American Thyroid Association (ATA) risk stratification. Material and Methods. 620 patients treated for a DTC were included in this study with a median follow-up duration of 6.1 years. All patients underwent total thyroidectomy followed by radioiodine ablation. Patients with positive anti-thyroglobulin antibodies were excluded. The predictive value of A-hTg was calculated by receiver operating characteristic curve (ROC curve) analysis. The Cox proportional hazard regression model, including the BRAF status, A-hTg, and ATA classification system, was assessed to evaluate the existing persistent disease risk. Results. Taken together, the BRAF status and A-hTg levels improve the ATA risk classification in all categories. In particular, in the low-risk ATA classification, only the combination of BRAFV600E+A-hTg>8.9ng/ml was associated with persistent disease (P=0.001, HR 60.2, CI 95% 5.28-687). In the intermediate-risk ATA classification, BRAFWT+A-hTg>8.9ng/ml was associated with persistent disease (P=0.029, HR 2.71, CI 95% 1.106-6.670) and BRAFV600E+A-hTg>8.9ng/ml was also associated with persistent disease (P<0.001, HR 5.001, CI 95% 2.318-10.790). In the high-risk ATA classification, both BRAFV600E+A-hTg<8.9ng/ml and BRAFV600E+A-hTg>8.9 ng/ml were associated with persistent disease (P=0.042, HR 5.963, CI 95% 1.069-33.255 and P=0.002, HR 11.564, CI 95% 2.543-52.576, respectively). Conclusions. The BRAF status and stimulated thyroglobulin levels at ablation time improve the ATA risk stratification of differentiated thyroid cancer; therefore, even A-hTg could be included in risk classification factors.

Risk Classification Systems and the Provision of Juvenile Aftercare

1993 ◽  
Vol 39 (1) ◽  
pp. 90-105 ◽  
Author(s):  
James R. Maupin
Keyword(s):  
Decision Making ◽  
Random Sample ◽  
Perceived Risk ◽  
Risk Classification ◽  
Classification Systems ◽  
Street Level ◽  
Parole Officers ◽  
Classification Score ◽  
Street Level Bureaucrats ◽  
Juvenile Parole

Juvenile aftercare decision-making systems that classify parolees according to perceived risk and needs are designed to render uniform the treatment of these individuals by juvenile parole officials. This article analyzes a system implemented by Arizona to determine if the intensity of supervision received by parolees differs as a function of classification score. Supervision of a random sample of 280 parolees was tracked for 90 days. The analysis indicates that intensity of supervision does not differ based on the classification score, suggesting that the instrument does not control the decision making of the street-level bureaucrats, the parole officers.

scholarly journals Long Non-Coding RNAs (lncRNAs) Are Highly Associated with Disease Characteristics and Outcome in Pediatric Acute Myeloid Leukemia - a COG and Tpaml Study

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2741-2741 ◽  
Author(s):  
Jenny L. Smith ◽  
Rhonda E. Ries ◽  
Jason E. Farrar ◽  
Todd A. Alonzo ◽  
Robert B. Gerbing ◽  
...  
Keyword(s):  
Predictive Power ◽  
Risk Groups ◽  
Risk Classification ◽  
Classification Systems ◽  
Low Risk ◽  
Training Set ◽  
Risk Status ◽  
Normal Bone ◽  
Childhood Aml ◽  
Non Coding Rnas

Childhood AML is a heterogeneous hematologic disease with a multitude of subtypes characterized by varying morphology, structural alterations, and recurrent mutations. Such heterogeneity and staggering number of genomic and transcriptional alterations has precluded appropriate risk classification. We investigated the expression of long non-coding RNAs (lncRNA) in childhood AML and explored its potential utility for more precise risk characterization at diagnosis. We inquired whether lncRNAs aberrantly expressed in AML compared to healthy normal bone marrows may be utilized for predicting outcome without knowledge of somatic variants, creating a variant-agnostic prognostic indicator. Ribodepleted RNA-sequencing data from normal bone marrows (N=68), as well as diagnostic primary samples (N=1300) from patients with detailed clinical annotations and outcome were included for study. To this end, the study population was divided into training (N=781), test (N=261), and validation (N=258) cohorts using blocked randomization. Upregulated lncRNAs compared to normal marrows in the training set (fold-change > 2, FDR < 0.05, Fig. 1A) were input for a LASSO cox proportional hazards regression which identified a set of 37 lncRNAs whose expression (log2 scale, TMM normalized) associated with patient outcome. The trained model coefficients were applied to the test and validation cohorts to produce a weighted sum of the 37 lncRNAs expression per patient (lncScores, range: -1.44 to +1.41). The distribution of lncScores revealed approximately equal numbers of patients with positive and negative scores in the training, test, and validation cohorts (Fig. 1B). In the training set, those with positive lncScores had an overall survival (OS) of 42.7% at 5-years from diagnosis compared to 76.3% for those with negative scores (hazard ratio (HR) = 3.15, p < 0.001). Positive lncScores were also associated with adverse event-free survival (EFS, HR = 2.47, p < 0.001). LncScore based outcome analysis in the independent test and validation cohorts showed nearly identical outcome results for OS (HR = 2.86 and 2.99 resp., p < 0.001) and EFS (HR = 2.37 and 2.35, p < 0.001, Fig. 1C) as was seen in the training set, demonstrating stability of the predictive power of the lncScore across independent cohorts. Next, the lncScore's performance was evaluated in relation to cyto/molecular risk groups (CMrisk: high, standard, and low) defined by karyotype, clinically relevant mutations, and cryptic fusions as presented previously (Cooper et al. ASH 2017). A multivariable cox regression model (N = 1300) that included lncScore, CMrisk, and white blood cell count revealed that both lncScore and CMrisk groups remained independent prognostic factors for OS (p < 0.001) and EFS (p ≤ 0.001), suggesting the lncRNA signature may provide additional prognostic information to that defined by CMrisk status. Application of the lncScore to the CMrisk groups demonstrated that 173 of the 541 of patients classified as CMrisk high (32%) would be reallocated to the standard risk arm based on negative lncScores (OS 57.3% vs 31.8%, p < 0.001). Similarly, 40% of patients with CMrisk standard (132/327) would be reclassified as low risk by the lncScore system (OS 73.8% vs 52.4%, p < 0.001). lncScores did not revise risk status in CMrisk low patients. The ribbon plot (Fig. 1E) demonstrates reallocation of patients using the integrated risk stratification system. Integration of the CMrisk and lncScore demonstrated that in combination the two risk classification systems can provide a more precise assessment of risk status, since both CMrisk high and CMrisk standard cohorts can be further stratified by the lncScore (Fig. 1D). The integrated approach provided a comprehensive risk classifier that incorporates both cytogenetic data, as well as transcriptional evidence, which benefits more than 1 out of 5 patients (23%, 305/1300) with a more accurate determination of risk at the time of diagnosis (Fig. 1F). This study demonstrates development and validation (in two independent cohorts) of a lncRNA based, variant-independent prognostic signature (p < 0.001) that can effectively partition patients into high and low risk groups at diagnosis. It can also significantly enhance the predictive power of conventional cyto/molecular markers for more precise prediction of outcome prior to the start of therapy. Disclosures Farrar: Novartis: Research Funding.

scholarly journals Splicing factor gene mutations in acute myeloid leukemia offer additive value if incorporated in current risk classification

2021 ◽  
Vol 5 (17) ◽  
pp. 3254-3265
Author(s):  
Inge van der Werf ◽  
Anna Wojtuszkiewicz ◽  
Manja Meggendorfer ◽  
Stephan Hutter ◽  
Constance Baer ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Prognostic Factor ◽  
Clinical Features ◽  
Myeloid Leukemia ◽  
Risk Classification ◽  
Classification Systems ◽  
Splicing Factor ◽  
Intermediate Risk ◽  
Molecular Abnormalities ◽  
Acute Myeloid

Abstract Splicing factor (SF) mutations are important contributors to the pathogenesis of hematological malignancies; however, their relevance in risk classification of acute myeloid leukemia (AML) warrants further investigation. To gain more insight into the characteristics of patients with AML carrying SF mutations, we studied their association with clinical features, cytogenetic and molecular abnormalities, and clinical outcome in a large cohort of 1447 patients with AML and high-risk myelodysplastic syndrome. SF mutations were identified in 22% of patients and were associated with multiple unfavorable clinical features, such as older age, antecedent myeloid disorders, and adverse risk factors (mutations in RUNX1 and ASXL1). Furthermore, they had significantly shorter event-free and overall survival. Notably, in European LeukemiaNet (ELN) 2017 favorable- and intermediate-risk groups, SF3B1 mutations were indicative of relatively poor prognosis. In addition, patients carrying concomitant SF mutations and RUNX1 mutations had a particularly adverse prognosis. In patients without any of the 4 most common SF mutations, RUNX1 mutations were associated with relatively good outcome, which was comparable to that of intermediate-risk patients. In this study, we propose that SF mutations be considered for incorporation into prognostic classification systems. First, SF3B1 mutations could be considered an intermediate prognostic factor when co-occurring with favorable risk features and as an adverse prognostic factor for patients currently categorized as having intermediate risk, according to the ELN 2017 classification. Second, the prognostic value of the current adverse factor RUNX1 mutations seems to be limited to its co-occurrence with SF mutations.

Risk Classification Systems for Drug Use During Pregnancy

Drug Safety ◽  
2000 ◽  
Vol 23 (3) ◽  
pp. 245-253 ◽  
Author(s):  
Antonio Addis ◽  
Sherin Sharabi ◽  
Maurizio Bonati
Keyword(s):  
Drug Use ◽  
Risk Classification ◽  
Classification Systems
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