Leukocytosis and Risk Stratification Assessment in Essential Thrombocythemia

2008 ◽  
Vol 26 (16) ◽  
pp. 2732-2736 ◽  
Author(s):  
Alessandra Carobbio ◽  
Elisabetta Antonioli ◽  
Paola Guglielmelli ◽  
Alessandro M. Vannucchi ◽  
Federica Delaini ◽  
...  
Keyword(s):  
Risk Factors ◽  
High Risk ◽  
Risk Stratification ◽  
Essential Thrombocythemia ◽  
Characteristic Curve ◽  
Risk Category ◽  
Vascular Events ◽  
Thrombotic Risk ◽  
C Statistic ◽  
Asymptomatic Patients

Purpose Established risk factors for thrombosis in essential thrombocythemia (ET) include age and previous vascular events. We aimed to refine this risk stratification by adding baseline leukocytosis. Patients and Methods We enrolled 657 patients with ET followed for a median of 4.5 years who developed 72 major thrombosis. Cox proportional hazard model was performed to analyze the thrombotic risk and to discriminate ET patients with or without thrombosis, multivariable C statistic index was used. We searched for leukocytes cutoff with the best sensitivity and specificity by a receiver operating characteristic curve. Results Results confirmed that age and prior events are independent risk factors for thrombosis and showed a gradient between baseline leukocytosis and thrombosis. On the contrary, no significant association was found either for JAK2V617F allele burden and for other laboratory parameters, including platelet number. In the model with conventional risk factors alone, C statistic ratio for total thrombosis was 0.63 and when leukocytosis was added, the change was small (C = 0.67). In contrast, in younger and asymptomatic patients (low-risk category), C statistic value indicated an high risk for thrombosis in patients with leukocytosis, similar to that calculated in conventionally defined high-risk group (C = 0.65). The best leukocyte cutoff values for predicting the events was found to be 9.4 (× 109/L). Conclusion We suggest to include baseline leukocytosis in the risk stratification of ET patients enrolled in clinical trials.

Leukocytosis and Risk Stratification Assessment in Essential Thrombocythemia.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 681-681
Author(s):  
Alessandra Carobbio ◽  
Elisabetta Antonioli ◽  
Alessandro M. Vannucchi ◽  
Federica Delaini ◽  
Vittoria Guerini ◽  
...  
Keyword(s):  
Risk Factors ◽  
Clinical Trials ◽  
Risk Factor ◽  
Risk Stratification ◽  
Essential Thrombocythemia ◽  
Reference Category ◽  
C Statistic ◽  
Conventional Risk Factors ◽  
Jak2v617f Allele Burden

Abstract Established risk factors for thrombosis in Essential Thrombocythemia (ET) including age and previous vascular events have been incorporated into algorithms for risk assessment in clinical trials. Our interest is now to refine this risk stratification by adding, to this established predictive model, leukocytosis, found to be a new risk factor for these events. For this purpose we used the C statistic estimate that defines, from a Cox multivariable model, the probability of concordance between leukocytosis and events among comparable patients during the time. C statistic values range from 0.5 (usefulness of the test) to 1 (perfect discriminatory test) and allow to evaluate the specificity and sensitivity of the test (leukocytosis) in analogy of the area under the curve (AUC) used for assessing the accuracy of the diagnostic tests. This analysis provides an assessment of the incremental role of leukocytosis, in addition to conventional risk factors, for discriminating ET patients with or without thrombosis. Finally, by a receiver operating characteristic (ROC) curve, we looked for the best cut-off of leukocytes to stratify patients into risk categories. During follow-up (median 4.5 years) 657 ET (PVSG and WHO diagnostic criteria) patients, 212 males, 445 females, median age 52 years (range 8–93), seen in two academic Italian institutions, had 72 major thrombotic events (28 venous, 44 arterial). Cox proportional hazard model was performed to analyse the thrombotic risk, adjusted for the following baseline variables: centre, sex, standard risk factors (age ≥ 60 years and/or prior thrombosis), hemoglobin, hematocrit, platelet, leukocytes and JAK2V617F allele burden. Results confirmed that age, prior events and leukocytosis are independent risk factors for thrombosis. Interestingly, a gradient between white blood cell (WBC) number and venous and arterial events was documented [Reference category: WBC <7.2 x109/L, WBC 7.2 − 8.7x109/L: RR=2.4, WBC 8.7 − 10.4x109/L: RR=2.7, WBC >10.4 x109/L: RR=3.0, all p-values <0.05]. On the contrary, no significant (p>0.05) association was found either for JAK2V617F allele burden [Reference category: JAK2V617F 0%, JAK2V617F 1–25%: RR=1.2, JAK2V617F 26–50%: RR=1.5, JAK2V617F >50%: RR=1.8] and for the other laboratory parameters. No centre-confounding effect was found. C statistics were then calculated on two Cox models for the prediction of major thrombosis in the follow-up of individual patients. The first model, including age over 60 years and/or prior thrombosis, showed a C statistic of 0.63. In the second one, by adding leukocytes at diagnosis, the C statistic was significantly improved (0.67). The best leukocyte cut-off values for predicting the events (ROC curve) ranged from 9.0 to 9.5 (x109/L), which corresponded to the highest sensitivity and specificity rates. In conclusion, we confirmed in this large retrospective cohort of ET patients that leukocytosis is an independent risk-factor for thrombosis. Moreover, we demonstrated by C statistic that leukocytosis has an incremental prognostic role in addition to conventional risk factors and found the best leukocytes cut-off able to discriminate between the group that will have thrombosis and the group that will not. These findings constitute a solid background to stratify patients in future clinical trials in ET.

Carnitine Deficiency in Epilepsy: Risk Factors and Treatment

1995 ◽  
Vol 10 (2_suppl) ◽  
pp. 2S32-2S39 ◽  
Author(s):  
David L. Coulter
Keyword(s):  
Risk Factors ◽  
High Risk ◽  
Preliminary Data ◽  
Metabolic Diseases ◽  
Drug Effects ◽  
Carnitine Deficiency ◽  
Free Carnitine ◽  
Specific Drug ◽  
Asymptomatic Patients ◽  
The Relationship

Numerous studies have shown that plasma carnitine levels are significantly lower in patients taking valproate than in controls. Free carnitine deficiency is not uncommon in these patients and also occurs in newborns with seizures and in patients taking other anticonvulsant drugs. Carnitine deficiency in epilepsy results from a variety of etiologic factors including underlying metabolic diseases, nutritional inadequacy, and specific drug effects. The relationship between carnitine deficiency and valproate-induced hepatotoxicity is unclear. Carnitine treatment does not always prevent the emergence of serious hepatotoxicity, but it does alleviate valproate-induced hyperammonemia. These studies suggest that specific risk factors for carnitine deficiency can be identified. Preliminary data suggest that carnitine treatment may benefit high-risk, symptomatic patients and those with free carnitine deficiency. Carnitine treatment is not likely to benefit low-risk, asymptomatic patients and those with normal carnitine levels. (J Child Neurol 1995;10(Suppl):2S32-2S39).

scholarly journals Risk stratification for intestinal dysbiosis in hospitalized adult patients according to the National Dysbiosis Survey (INDIS)

2020 ◽  
Vol 2 (35) ◽  
pp. 149-159
Author(s):  
Aline Okipney ◽  
Jéssica Romanelli Amorim de Souza ◽  
Antonio Carlos Ligocki Campos ◽  
Leticia Fuganti Campos ◽  
Paula Rodrigues Anjo ◽  
...  
Keyword(s):  
Risk Factors ◽  
High Risk ◽  
Risk Stratification ◽  
Elderly Patients ◽  
Univariate Analysis ◽  
Intestinal Flora ◽  
Adult Patients ◽  
Therapeutic Interventions ◽  
Intestinal Dysbiosis ◽  
Very High

Introduction: The intestinal microbiota has a symbiotic relationship with the human being. Its alteration, known as dysbiosis, can result in several diseases. Some risk factors may predict the occurrence of this condition. The purpose of this study was to evaluate the effectiveness of the National Dysbiosis Survey (INDIS) in the risk stratification of hospitalized adult patients that presented with intestinal dysbiosis. Methods: 100 patients hospitalized at the Hospital das Clínicas da UFPR were interviewed through INDIS. In this questionnaire, risk factors for dysbiosis of each patient were established and the dysbiosis degree was stratified in low, medium, high, and very high risk. Results: Most patients were classified as medium (43%) and high risk (39%) of dysbiosis. The univariate analysis revealed an association between the degree of dysbiosis and elderly patients (p=0.034), number of comorbidities (p<0.001), presence of diarrhea or constipation (p<0.001) and medication in use [antibiotic and/or proton pump inhibitor (PII); p<0.001]. In the multivariate analysis, the most important influence in classification was the presence of diarrhea or constipation (OR=3.00, 95% CI [1.73, 5.21] p<0.001) and medication in use (Score 3: OR = 53.4, 95% CI [2.73, 1045.5], p=0.009 and Score 4-8: OR = 1709.1, 95% CI [50.27, 58103.5] p<0.001), both independent predictors of high and very high risk of dysbiosis. Conclusion: The risk degree of intestinal dysbiosis is greater in the presence of diarrhea or constipation, the use of antibiotics and/or PII, and in elderly patients. Once the risks of dysbiosis have been defined, INDIS proved to be an effective and rapid tool for risk stratification of dysbiosis in the study population, future studies should determine the relevance of therapeutic interventions with the purpose of normalizing the intestinal flora.

Venous Thromboembolic Diseases

2014 ◽  
pp. 346-355
Author(s):  
Gregory Piazza ◽  
Samuel Z. Goldhaber
Keyword(s):  
Risk Factors ◽  
High Risk ◽  
Risk Stratification ◽  
Laboratory Testing ◽  
Clinical Findings ◽  
Venous Thromboembolic ◽  
Long Term Consequences ◽  
Practical Recommendations

This chapter reviews the pathophysiology of VTE, including its risk factors and long-term consequences. Diagnostic algorithms that integrate clinical findings, laboratory testing, and imaging are described. The role of risk stratification for identification of high-risk PE patients is highlighted. Options for the management of VTE are reviewed. Finally, practical recommendations for the prevention of VTE are provided.

P4688Additional role of unmodifiable risk factors in pulmonary arterial hypertension risk stratification according to current ESC/ERS guidelines

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
E Zuffa ◽  
F Dardi ◽  
M Palazzini ◽  
E Gotti ◽  
A Rinaldi ◽  
...  
Keyword(s):  
Risk Factors ◽  
Pulmonary Arterial Hypertension ◽  
High Risk ◽  
Risk Stratification ◽  
Arterial Hypertension ◽  
Specific Treatment ◽  
Low Risk ◽  
P Value ◽  
Pulmonary Arterial

Abstract Background Current pulmonary hypertension (PH) guidelines stratify the risk of patients with pulmonary arterial hypertension (PAH) using a multiparametric approach. Anyway, the role of unmodifiable risk factors is not taken into account. Purpose The aim of this study was to evaluate the role of unmodifiable risk factors (age, gender, PAH aetiology) in PAH risk stratification using the recently proposed simplified risk table and to test if these factors influence the response to PAH-specific treatment. Methods All patients with PAH referred to a single centre were included from 2003 to 2017. We applied a simplified risk assessment strategy using the following criteria: WHO functional class, 6-min walking distance, right atrial pressure or brain natriuretic peptide plasma levels and cardiac index (CI) or mixed venous oxygen saturation (SvO2). The last 2 criteria were based on which parameter was available; if both were available the worst was chosen. Risk strata were defined as: Low risk= at least 3 low risk and no high-risk criteria; High risk= at least 2 high risk criteria including CI or SvO2; Intermediate risk= definitions of low or high risk not fulfilled. Then we performed multivariate Cox analysis to evaluate what are the independent predictors of survival (age, gender, PAH aetiology together with the recently proposed simplified PAH risk table) and we tested if these factors influence the response to PAH specific therapy comparing the % improvement of hemodynamic parameters from baseline to 3–4 months after starting treatment. Wilcoxon-Mann-Whitney test was used for comparisons. Results Six hundreds and twenty-one treatment-naïve patients were enrolled. Age [HR (95% CI) = 1.022 (1.014–1.030); p-value <0.001], male gender [HR (95% CI) = 1.881 (1.479–2.392); p-value <0.001] and connective tissue disease (CTD)-PAH aetiology [HR (95% CI)= 2.278 (1.733–2.995); p-value <0.001] were all independent predictors of prognosis in patients with PAH together with the recently validated simplified PAH risk table [HR (95% CI) = 2.161 (1.783–2.618); p-value <0.001] but they didn't significantly influence the response to PAH specific treatment as shown in the Figure. Figure 1 Conclusions Age, gender and CTD-PAH aetiology significantly influence prognosis together with the recently validated simplified PAH risk table but don't significantly influence the response to PAH-specific treatment. Acknowledgement/Funding None

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.

scholarly journals Hydroxycarbamide Plus Aspirin Versus Aspirin Alone in Patients With Essential Thrombocythemia Age 40 to 59 Years Without High-Risk Features

2018 ◽  
Vol 36 (34) ◽  
pp. 3361-3369 ◽  
Author(s):  
Anna L. Godfrey ◽  
Peter J. Campbell ◽  
Cathy MacLean ◽  
Georgina Buck ◽  
Julia Cook ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Risk Factors ◽  
Platelet Count ◽  
High Risk ◽  
Vascular Events ◽  
End Point ◽  
High Risk Factors ◽  
Patient Reported

Purpose Cytoreductive therapy is beneficial in patients with essential thrombocythemia (ET) at high risk of thrombosis. However, its value in those lacking high-risk features remains unknown. This open-label, randomized trial compared hydroxycarbamide plus aspirin with aspirin alone in patients with ET age 40 to 59 years and without high-risk factors or extreme thrombocytosis. Patients and Methods Patients were age 40 to 59 years and lacked a history of ischemia, thrombosis, embolism, hemorrhage, extreme thrombocytosis (platelet count ≥ 1,500 × 109/L), hypertension, or diabetes requiring therapy. In all, 382 patients were randomly assigned 1:1 to hydroxycarbamide plus aspirin or aspirin alone. The composite primary end point was time to arterial or venous thrombosis, serious hemorrhage, or death from vascular causes. Secondary end points were time to first arterial or venous thrombosis, first serious hemorrhage, death, incidence of transformation, and patient-reported quality of life. Results After a median follow-up of 73 months and a total follow-up of 2,373 patient-years, there was no significant difference between the arms in the likelihood of patients reaching the primary end point (hazard ratio, 0.98; 95% CI, 0.42 to 2.25; P = 1.0). The incidence of significant vascular events was low, at 0.93 per 100 patient-years (95% CI, 0.61 to 1.41). There were also no differences in overall survival; in the composite end point of transformation to myelofibrosis, acute myeloid leukemia, or myelodysplasia; in adverse events; or in patient-reported quality of life. Conclusion In patients with ET age 40 to 59 years and lacking high-risk factors for thrombosis or extreme thrombocytosis, preemptive addition of hydroxycarbamide to aspirin did not reduce vascular events, myelofibrotic transformation, or leukemic transformation. Patients age 40 to 59 years without other clinical indications for treatment (such as previous thrombosis or hemorrhage) who have a platelet count < 1,500 × 109/L should not receive cytoreductive therapy.

scholarly journals Learning Data-Driven Patient Risk Stratification Models for Clostridium difficile

2014 ◽  
Vol 1 (2) ◽  
Author(s):  
Jenna Wiens ◽  
Wayne N. Campbell ◽  
Ella S. Franklin ◽  
John V. Guttag ◽  
Eric Horvitz
Keyword(s):  
Risk Factors ◽  
Clostridium Difficile ◽  
Risk Stratification ◽  
Characteristic Curve ◽  
Data Driven ◽  
First Year ◽  
High Risk Population ◽  
Urban Hospital ◽  
Small Set ◽  
Validation Set

Abstract Background.  Although many risk factors are well known, Clostridium difficile infection (CDI) continues to be a significant problem throughout the world. The purpose of this study was to develop and validate a data-driven, hospital-specific risk stratification procedure for estimating the probability that an inpatient will test positive for C difficile. Methods.  We consider electronic medical record (EMR) data from patients admitted for ≥24 hours to a large urban hospital in the U.S. between April 2011 and April 2013. Predictive models were constructed using L2-regularized logistic regression and data from the first year. The number of observational variables considered varied from a small set of well known risk factors readily available to a physician to over 10 000 variables automatically extracted from the EMR. Each model was evaluated on holdout admission data from the following year. A total of 34 846 admissions with 372 cases of CDI was used to train the model. Results.  Applied to the separate validation set of 34 722 admissions with 355 cases of CDI, the model that made use of the additional EMR data yielded an area under the receiver operating characteristic curve (AUROC) of 0.81 (95% confidence interval [CI], .79–.83), and it significantly outperformed the model that considered only the small set of known clinical risk factors, AUROC of 0.71 (95% CI, .69–.75). Conclusions.  Automated risk stratification of patients based on the contents of their EMRs can be used to accurately ide.jpegy a high-risk population of patients. The proposed method holds promise for enabling the selective allocation of interventions aimed at reducing the rate of CDI.

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