scholarly journals Prediction of Venous Thromboembolism Based on Clinical and Genetic Factors

2020 ◽  
Author(s):  
David A. Kolin ◽  
Scott Kulm ◽  
Olivier Elemento
Keyword(s):  
Risk Factors ◽  
Venous Thromboembolism ◽  
High Risk ◽  
Genetic Risk ◽  
Genetic Factors ◽  
Hazard Ratio ◽  
Low Risk ◽  
Clinical Risk Factors ◽  
Clinical Risk ◽  
Increased Risk

BACKGROUNDBoth clinical and genetic factors drive the risk of venous thromboembolism. However, whether clinically recorded risk factors and genetic variants can be combined into a clinically applicable predictive score remains unknown.METHODSUsing Cox proportional-hazard models, we analyzed the association of risk factors with the likelihood of venous thromboembolism in U.K. Biobank, a large prospective cohort. We created a novel ten point clinical score using seven established clinical risk factors for venous thromboembolism. We also generated a polygenic risk score of 21 single nucleotide polymorphisms to quantify genetic risk. The genetic score was categorized into high risk (top two deciles of scores), intermediate risk (deciles three to eight), and low risk (lowest two deciles). The discrete clinical score led to the following approximate decile categorizations: high risk (5 to 10 points), intermediate risk (3 to 4 points), and low risk (0 to 2 points).RESULTSAmongst the 502,536 participants in the U.K. Biobank, there were 4,843 events of venous thromboembolism. Analyses of established clinical risk factors and the most commonly used medications revealed that participants were at decreased risk of venous thromboembolism if they had ever used oral contraceptive pills (hazard ratio, 0.88; 95% confidence interval [CI], 0.79 to 0.99) or if they currently used bendroflumethiazide (hazard ratio, 0.84; 95% CI, 0.74 to 0.95), cod liver oil capsules (hazard ratio, 0.87; 95% CI, 0.77 to 0.99), or atenolol (hazard ratio, 0.79; 95% CI, 0.68 to 0.91). Participants were at significantly increased risk of venous thromboembolism if they were at high clinical risk (hazard ratio, 5.98; 95% CI, 5.43 to 6.59) or high genetic risk (hazard ratio, 2.28; 95% CI, 2.07 to 2.51) relative to participants at low clinical or genetic risk, respectively. Combining clinical risk factors with genetic risk factors produced a model that better predicted risk of venous thromboembolism than either model alone (P<0.001). Participants at high clinical and genetic risk in the combined score had over an eightfold increased risk of venous thromboembolism relative to participants at low risk (hazard ratio, 8.27; 95% CI 7.59 to 9.00).CONCLUSIONSBy assessing venous thromboembolic events in over 500,000 participants, we identified several known and novel associations between risk factors and venous thromboembolism. Participants in the high risk group of a combined score, consisting of clinical and genetic factors, were over eight times more likely to experience venous thromboembolism than participants in the low risk group.

scholarly journals Prediction of primary venous thromboembolism based on clinical and genetic factors within the U.K. Biobank

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
David A. Kolin ◽  
Scott Kulm ◽  
Olivier Elemento
Keyword(s):  
Risk Factors ◽  
Venous Thromboembolism ◽  
Risk Score ◽  
Genetic Risk ◽  
Genetic Factors ◽  
External Validation ◽  
Predictive Score ◽  
Polygenic Risk Score ◽  
Genetic Components ◽  
Increased Risk

AbstractBoth clinical and genetic factors drive the risk of venous thromboembolism. However, whether clinically recorded risk factors and genetic variants can be combined into a clinically applicable predictive score remains unknown. Using Cox proportional-hazard models, we analyzed the association of risk factors with the likelihood of venous thromboembolism in U.K. Biobank, a large prospective cohort. We then created a polygenic risk score of 36 single nucleotide polymorphisms and a clinical score determined by age, sex, body mass index, previous cancer diagnosis, smoking status, and fracture in the last 5 years. Participants were at significantly increased risk of venous thromboembolism if they were at high clinical risk (subhazard ratio, 4.37 [95% CI, 3.85–4.97]) or high genetic risk (subhazard ratio, 3.02 [95% CI, 2.63–3.47]) relative to participants at low clinical or genetic risk, respectively. The combined model, consisting of clinical and genetic components, was significantly better than either the clinical or the genetic model alone (P < 0.001). Participants at high risk in the combined score had nearly an eightfold increased risk of venous thromboembolism relative to participants at low risk (subhazard ratio, 7.51 [95% CI, 6.28–8.98]). This risk score can be used to guide decisions regarding venous thromboembolism prophylaxis, although external validation is needed.

scholarly journals A risk model for relapsed/refractory aggressive NHL integrating clinical risk factors and pretransplant Deauville score

2020 ◽  
Vol 4 (22) ◽  
pp. 5762-5771
Author(s):  
Ho-Young Yhim ◽  
Yael Eshet ◽  
Ur Metser ◽  
Chae-Hong Lim ◽  
Katherine Lajkosz ◽  
...  
Keyword(s):  
Risk Factors ◽  
High Risk ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Salvage Chemotherapy ◽  
Low Risk ◽  
Clinical Risk Factors ◽  
Intermediate Risk ◽  
Clinical Risk ◽  
Deauville Score

Abstract There are limited data regarding the combined value of the pretransplant Deauville score (DS) from a positron emission tomography scan and clinical risk factors in patients with relapsed/refractory aggressive non-Hodgkin lymphoma (NHL). We performed a retrospective analysis to assess the prognostic role of pretransplant DS in patients with relapsed/refractory aggressive NHL who underwent salvage chemotherapy and autologous stem cell transplantation (ASCT). We identified 174 eligible patients between January 2013 and March 2019. In multivariable analysis, pretransplant DS, B symptoms, and secondary International Prognostic Index (sIPI) were independent risk factors for event-free survival (EFS). These variables were used to derive an integrated risk score that categorized 166 patients with available information for all risk factors into 3 groups: low (n = 92; 55.4%), intermediate (n = 48; 28.9%), and high (n = 26; 15.7%). The new prognostic index showed a strong association with EFS (low-risk vs intermediate-risk hazard ratio [HR], 3.94; 95% confidence interval [CI], 2.16-7.17; P &lt; .001; low-risk vs high-risk HR, 10.83; 95% CI, 5.81-20.19; P &lt; .001) and outperformed models based on clinical risk factors or DS alone. These results were validated in 60 patients from an independent external cohort (low-risk vs intermediate-risk HR, 4.04; 95% CI, 1.51-10.82; P = .005; low-risk vs high-risk HR, 10.49; 95% CI, 4.11-26.73; P &lt; .001). We propose and validate a new prognostic index that risk-stratifies patients undergoing salvage chemotherapy followed by ASCT, thereby identifying patients at high risk for posttransplant treatment failure.

scholarly journals Clinical Application of a Novel Genetic Risk Score for Ischemic Stroke in Patients with Cardiometabolic Disease

Circulation ◽  
2020 ◽  
Author(s):  
Nicholas A. Marston ◽  
Parth N. Patel ◽  
Frederick K. Kamanu ◽  
Francesco Nordio ◽  
Giorgio M. Melloni ◽  
...  
Keyword(s):  
Risk Factors ◽  
Atrial Fibrillation ◽  
Ischemic Stroke ◽  
Genetic Risk ◽  
Genetic Risk Score ◽  
Clinical Risk Factors ◽  
Cardiometabolic Disease ◽  
Clinical Risk ◽  
Hazard Ratios ◽  
Increased Risk

Background: Genome-wide association studies have identified single nucleotide polymorphisms (SNPs) that are associated with an increased risk of stroke. We sought to determine whether a genetic risk score (GRS) could identify subjects at higher risk for ischemic stroke after accounting for traditional clinical risk factors in five trials across the spectrum of cardiometabolic disease. Methods: Subjects who had consented for genetic testing and who were of European ancestry from the ENGAGE AF-TIMI 48, SOLID-TIMI 52, SAVOR-TIMI 53, PEGASUS-TIMI 54, and FOURIER trials were included in this analysis. A set of 32 SNPs associated with ischemic stroke was used to calculate a GRS in each patient and identify tertiles of genetic risk. A Cox model was used to calculate hazard ratios for ischemic stroke across genetic risk groups, adjusted for clinical risk factors. Results: In 51,288 subjects across the five trials, a total of 960 subjects had an ischemic stroke over a median follow-up period of 2.5 years. After adjusting for clinical risk factors, increasing genetic risk was strongly and independently associated with increased risk for ischemic stroke (p-trend=0.009). When compared to individuals in the lowest third of genetic risk, individuals in the middle and top tertiles of genetic risk had adjusted hazard ratios of 1.15 (95% CI 0.98-1.36) and 1.24 (95% CI 1.05-1.45) for ischemic stroke, respectively. Stratification into subgroups revealed the performance of the GRS appeared stronger in the primary prevention cohort with an adjusted HR for the top versus lowest tertile of 1.27 (95% CI 1.04-1.53), compared with an adjusted HR of 1.06 (95% CI 0.81-1.41) in subjects with prior stroke. In an exploratory analysis of patients with atrial fibrillation and CHA 2 DS 2 -VASc of 2, high genetic risk conferred a 4-fold higher risk of stroke and an absolute risk equivalent to those with CHA 2 DS 2 -VASc of 3. Conclusions: Across a broad spectrum of subjects with cardiometabolic disease, a 32-SNP GRS was a strong, independent predictor of ischemic stroke. In patients with atrial fibrillation but lower CHA 2 DS 2 -VASc scores, the GRS identified patients with risk comparable to those with higher CHA 2 DS 2 -VASc scores.

Prediction of Preeclampsia and Delivery of Small for Gestational Age Babies Based on a Combination of Clinical Risk Factors in High-Risk Women

2010 ◽  
Vol 30 (1) ◽  
pp. 58-73 ◽  
Author(s):  
Paul T. Seed ◽  
Lucy C. Chappell ◽  
Michael A. Black ◽  
Katrina K. Poppe ◽  
Yuan-Chun Hwang ◽  
...  
Keyword(s):  
Risk Factors ◽  
High Risk ◽  
Gestational Age ◽  
Small For Gestational Age ◽  
Clinical Risk Factors ◽  
High Risk Women ◽  
Clinical Risk

scholarly journals Simple electrocardiographic measures improve sudden arrhythmic death prediction in coronary disease

2020 ◽  
Vol 41 (21) ◽  
pp. 1988-1999 ◽  
Author(s):  
Neal A Chatterjee ◽  
Jani T Tikkanen ◽  
Gopi K Panicker ◽  
Dhiraj Narula ◽  
Daniel C Lee ◽  
...  
Keyword(s):  
Risk Factors ◽  
High Risk ◽  
Risk Stratification ◽  
Validation Cohort ◽  
Clinical Risk Factors ◽  
Left Ventricular Ejection ◽  
Derivation Cohort ◽  
Arrhythmic Death ◽  
Clinical Risk ◽  
Ecg Score

Abstract Aims To determine whether the combination of standard electrocardiographic (ECG) markers reflecting domains of arrhythmic risk improves sudden and/or arrhythmic death (SAD) risk stratification in patients with coronary heart disease (CHD). Methods and results The association between ECG markers and SAD was examined in a derivation cohort (PREDETERMINE; N = 5462) with adjustment for clinical risk factors, left ventricular ejection fraction (LVEF), and competing risk. Competing outcome models assessed the differential association of ECG markers with SAD and competing mortality. The predictive value of a derived ECG score was then validated (ARTEMIS; N = 1900). In the derivation cohort, the 5-year cumulative incidence of SAD was 1.5% [95% confidence interval (CI) 1.1–1.9] and 6.2% (95% CI 4.5–8.3) in those with a low- and high-risk ECG score, respectively (P for Δ &lt; 0.001). A high-risk ECG score was more strongly associated with SAD than non-SAD mortality (adjusted hazard ratios = 2.87 vs. 1.38 respectively; P for Δ = 0.003) and the proportion of deaths due to SAD was greater in the high vs. low risk groups (24.9% vs. 16.5%, P for Δ = 0.03). Similar findings were observed in the validation cohort. The addition of ECG markers to a clinical risk factor model inclusive of LVEF improved indices of discrimination and reclassification in both derivation and validation cohorts, including correct reclassification of 28% of patients in the validation cohort [net reclassification improvement 28 (7–49%), P = 0.009]. Conclusion For patients with CHD, an externally validated ECG score enriched for both absolute and proportional SAD risk and significantly improved risk stratification compared to standard clinical risk factors including LVEF. Clinical Trial Registration https://clinicaltrials.gov/ct2/show/NCT01114269. ClinicalTrials.gov ID NCT01114269.

Clinical Predictors of Venous Thromboembolism during Therapy for Childhood Acute Lymphoblastic Leukemia

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1182-1182 ◽  
Author(s):  
Marion K Mateos ◽  
Toby N. Trahair ◽  
Chelsea Mayoh ◽  
Pasquale M Barbaro ◽  
Rosemary Sutton ◽  
...  
Keyword(s):  
Risk Factors ◽  
Risk Factor ◽  
Venous Thromboembolism ◽  
Cox Regression ◽  
Lymphoblastic Leukemia ◽  
Clinical Risk Factors ◽  
Clinical Factors ◽  
Clinical Risk ◽  
Cancer Project ◽  
Prophylactic Anticoagulation

Abstract Venous thromboembolism (VTE) is an unpredictable and life-threatening toxicity that occurs early in acute lymphoblastic leukemia (ALL) therapy. The incidence is approximately 5% in children diagnosed with ALL [Caruso et al. Blood. 2006;108(7):2216-22], which is higher than in other pediatric cancer types [Athale et al. Pediatric Blood & Cancer. 2008;51(6):792-7]. Clinical risk factors for VTE in children during ALL therapy include older age and the use of asparaginase. We hypothesized that there may be additional risk factors that can modify VTE risk, beyond those previously reported [Mitchell et al. Blood. 2010;115(24):4999-5004]. We sought to define early predictive clinical factors that could select a group of children at highest risk of VTE, with possible utility in an interventional trial of prophylactic anticoagulation. We conducted a retrospective study of 1021 Australian children, aged 1-18 years, treated between 1998-2013 on successive BFM-based ALL therapies. Patient records were reviewed to ascertain incidence of VTE; and to systematically document clinical variables present at diagnosis and during induction/consolidation phases of therapy. The CTCAE v4.03 system was used for grading of VTE events. Multivariate logistic and cox regression were used to determine significant clinical risk factors associated with VTE (SPSS v23.0). All P values were 2-tailed, significance level <.05. The incidence of on-treatment VTE was 5.09% [96% ≥Grade 2 (CTCAE v4.0)]. Age ≥10 years [P =.048, HR 1.96 (95% confidence interval= 1.01-3.82)], positive blood culture in induction/consolidation [ P =.009, HR 2.35 (1.24-4.46)], extreme weight at diagnosis <5th or >95th centile [ P =.028, HR 2.14 (1.09-4.20)] and elevated peak gamma-glutamyl transferase (GGT) >5 x upper limit normal in induction/consolidation [ P =.018, HR 2.24 (1.15-4.36)] were significantly associated with VTE in multivariate cox regression modeling. The cumulative incidence of VTE, if all 4 clinical risk factors in our model were present, was 33.33%, which is significantly greater than the incidence of VTE for a patient without any risk factors (1.62%, P <.001). These 4 clinical factors could be used as a basis for assigning thromboprophylaxis in children with ALL. Our model detected 80% (42/52) of all VTE events by incorporating one or more risk factors. An equal proportion of patients eventually developing VTE could be predicted by weight and age ≥10 years; or later bacteremia and elevated GGT. Bacteremia, when present as a risk factor, preceded VTE in 80% of cases (20/25 cases) at a median of 29 days before VTE (range 3-668 days). The negative predictive value (NPV), specificity and sensitivity for the 4 risk factor model were 98.38%, 98.70% and 28.57% respectively. If 3 specified risk factors were included in the algorithm, such as 2 baseline and one treatment-related variable, the incidence of VTE was ≥25%, NPV 98.38%, specificity ≥96.19% and sensitivity 80%. The high NPV and high specificity mean the model can successfully exclude children who are not at increased risk of VTE. The challenge is to balance unnecessary exposure to anticoagulation against the risk of development of VTE. We have identified novel clinical risk factors in induction/consolidation - positive blood culture, hepatic enzymatic elevation and extreme weight at diagnosis- that may highlight risk mechanisms related to VTE pathogenesis. Our predictive model can define a group at highest risk of VTE who may benefit from randomized trials of prophylactic anticoagulation in childhood ALL therapy. Acknowledgments: The authors acknowledge support from the Kids Cancer Alliance (a Translational Cancer Research Centre of Cancer Institute NSW), Cancer Institute New South Wales, Royal Australasian College of Physicians - Kids Cancer Project Research Entry Scholarship, Cancer Therapeutics CRC (CTx) PhD Clinician Research Top-Up Scholarship, The Kids Cancer Project, Australian and New Zealand Children's Haematology Oncology Group, ASSET study members, data managers and clinical research associates at each site. Disclosures No relevant conflicts of interest to declare.

scholarly journals Identification of patients at increased risk of suicide in hepatobiliary and pancreatic cancer: an analysis of epidemiologic and clinical risk factors

HPB ◽  
2017 ◽  
Vol 19 ◽  
pp. S55
Author(s):  
P. Martinez Quinones ◽  
A. Talukder ◽  
N. Walsh ◽  
A. Lawson ◽  
A. Jones ◽  
...  
Keyword(s):  
Risk Factors ◽  
Pancreatic Cancer ◽  
Clinical Risk Factors ◽  
Clinical Risk ◽  
Increased Risk

scholarly journals Integration of genetic and clinical risk factors improves prognostication in relapsed childhood B-cell precursor acute lymphoblastic leukemia

Blood ◽  
2016 ◽  
Vol 128 (7) ◽  
pp. 911-922 ◽  
Author(s):  
Julie A. E. Irving ◽  
Amir Enshaei ◽  
Catriona A. Parker ◽  
Rosemary Sutton ◽  
Roland P. Kuiper ◽  
...  
Keyword(s):  
Risk Factors ◽  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Chromosomal Abnormalities ◽  
Lymphoblastic Leukemia ◽  
Clinical Risk Factors ◽  
Clinical High Risk ◽  
Cell Precursor ◽  
Clinical Risk ◽  
Key Points

Key Points Chromosomal abnormalities predict outcome after relapse in BCP-ALL, and high-risk cytogenetics takes precedence over clinical risk factors. Patients with mutations or deletions targeting TP53, NR3C1, BTG1, and NRAS were associated with clinical high risk and an inferior outcome.

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