Christel Castelli

Université de Nîmes, Nismes, Languedoc-Roussillon, France

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Publications (16)51.38 Total impact

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    ABSTRACT: Although predicting the risk of venous thrombosis (VT) in an individual from a family with inherited thrombophilia is of major importance, it is often not feasible. To develop a simple risk assessment model that improves prediction of the risk of VT for individuals of families with inherited thrombophilia. 1201 relatives from 430 families with inherited thrombophilia (deficiencies of antithrombin, protein C or protein S, and the factor V Leiden and F2 20210A mutations) were recruited at the referral center for thrombophilia in Marseilles, France, from 1986 to 2008. One hundred and twenty-two individuals had a personal history of VT. Sixteen preselected clinical and laboratory variables were used to derive the VT risk score. The scores based on the 16 variables and on the five most strongly associated variables performed similarly (areas under receiver operating characteristic curves of 0.85 and 0.83, respectively). For the five-variable score, named the MARNI score, derived from family history score of VT, von Willebrand factor antigen levels, age, severity of thrombophilia, and FGG rs2066865, the risk of VT ranged from 0.2% for individuals with a score of 0 (n = 186) to > 70% for individuals with a score of ≥ 7 (n = 27). The model was validated with an internal bootstrap method. With the use of a simple scoring system, assessment of the risk of VT in subjects from families with inherited thrombophilia can be greatly improved. External validation is now needed to replicate these findings.
    Journal of Thrombosis and Haemostasis 02/2014; 12(2):138-146. · 6.08 Impact Factor
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    ABSTRACT: AIMS: We aimed to assess the cost effectiveness of the sirolimus-eluting stent (SES) in diabetic and non-diabetic patients vs. bare metal stents (BMS). METHODS: EVASTENT was a matched cohort registry of patients undergoing revascularization exclusively with SES; for each diabetic patient (db+) included, stratified according to single (SVD) or multiple (MVD) vessel disease, a non-diabetic patient (db-) was subsequently included. Efficacy, safety and cost data were obtained from the SES database, and then data from the BMS group were derived by using an original method of transition probabilities of events (Markov model and Monte Carlo simulations) if BMS had been implanted in the same patient, over a 3-year time period. Sensitivity analysis was performed by varying the price difference between BMS and SES from 2008 to 2012. RESULTS: In this study, 1731 patients were included with 97% complete follow-up at 3-years. In 2008, compared to BMS the SES was cost effective only in MVD db+ (7494€ per avoided revascularization (PAR) vs. >10,000€ in other groups). In 2012, after a reduction in the price difference between SES and BMS, SES were cost effective in MVD db+ (-891), SVD db+ (3519), MVD db- (3050), and SVD db- (6329) patients. Otherwise, the cardiovascular mortality rate was higher (p<0.0001) in MVD db+ than in SVD db+, MVD db- and SVD db-. CONCLUSION: The SES is now cost effective in diabetic and non-diabetic patients, after a favorable price evolution between drug eluting and bare metal stents.
    International journal of cardiology 01/2013; · 6.18 Impact Factor
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    ABSTRACT: The present study was designed to assess the effect of genetic variants on chronic biological response to prasugrel and bleeding complications. CYP2C19*2 loss-of-function allele and CYP2C19*17 gain-of-function allele have been linked with response to clopidogrel, but preliminary data did not show any significant influence of these alleles on prasugrel effect. A total of 213 patients undergoing successful coronary stenting for acute coronary syndrome and discharged with prasugrel 10 mg daily were included. Prasugrel response was assessed at 1 month with the platelet reactivity index (PRI) vasodilator-stimulated phosphoprotein (VASP) and high on-treatment platelet reactivity (HTPR) defined as PRI VASP > 50% and hyper-response as PRI VASP <75th percentile (PRI VASP < 17%). CYP2C19*2 and CYP2C19*17 genotyping were performed. Carriers of loss-of-function *2 allele had significantly higher PRI VASP than noncarriers (33 ± 15% vs. 27 ± 14%, p = 0.03) and higher rate of HTPR (16% vs. 4%, p = 0.01). Conversely, carriers of *17 gain-of-function allele had significantly lower PRI VASP than noncarriers (25 ± 13% vs. 31 ± 15%, p = 0.03, p = 0.03), lower rate of HTPR (1% vs. 10%, p = 0.02), higher rate of hyper-response (34% vs. 21%, p = 0.02), and higher rate of bleeding complications than noncarriers: 23% versus 11%, (odds ratio [95% confidence interval]: 2.5 [1.2 to 5.4]; p = 0.02). No significant influence of genotypes on platelet reactivity assessed by adenosine diphosphate-induced platelet aggregation was observed. The present study shows a significant influence of CYP2C19*2 and *17 alleles on response to chronic treatment by prasugrel 10 mg daily and occurrence of bleeding complications.
    JACC. Cardiovascular Interventions 12/2012; 5(12):1280-7. · 1.07 Impact Factor
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    ABSTRACT: The aim of this study was to evaluate platelet reactivity and 30-day bleeding events in patients treated with prasugrel 10 mg after acute coronary syndromes. A total of 444 patients with acute coronary syndromes treated with percutaneous coronary intervention and prasugrel 10 mg/day were monitored by measurement of the vasodilator-stimulated phosphoprotein (VASP) index 2 to 4 weeks after hospital discharge. Platelet reactivity was also assessed using the VerifyNow P2Y(12) assay and light transmission aggregometry. Bleeding events (per the Bleeding Academic Research Consortium [BARC] definition) and ischemic events (death, myocardial infarction, and definite stent thrombosis) were collected over 30 days of follow-up. Two thirds of the patients presented with ST-segment elevation myocardial infarctions, 28.8% had diabetes, and 12.4% were aged >75 years. High on-treatment platelet reactivity according to 3 prespecified definitions (VASP index ≥50%, platelet reactivity ≥235 P2Y(12) reaction units, and residual platelet reactivity ≥46.2%) was found in 6.8%, 3.4%, and 3.2% of patients, respectively. Obesity (body mass index >30 kg/m(2)) and multivessel disease were the only independent factors associated with high on-treatment platelet reactivity (p = 0.006 and p = 0.045, respectively). At 30 days, there was no major bleeding complication (BARC grade 3 or 5), and 1.6% of patients had recurrent ischemic events. Nuisance bleeding (BARC grade 1) and minor bleeding (BARC grade 2) occurred in 14.2% (n = 63) and 2.5% (n = 11) of patients, respectively, but were not predicted by VASP index. In conclusion, patients with acute coronary syndromes receiving maintenance doses of prasugrel have low rates of HPR and ischemic events within the first month. Minor or minimal bleeding is frequent, but not major bleeding. VASP was poorly correlated with the risk for minor or minimal bleeding.
    The American journal of cardiology 10/2012; · 3.58 Impact Factor
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    ABSTRACT: We aimed to study the association among ABO blood group, von Willebrand factor, factor VIII plasma levels, and the risk of venous thrombosis (VT) in a cohort of 1774 relatives from 500 families with inherited thrombophilia. One hundred sixty-one of the 1774 relatives had a VT. Different risk groups were formed: no, low-(factor V Leiden or F2G20210A heterozygous carriers), and high-risk thrombophilia (antithrombin, protein C, protein S, factor V Leiden, or F2G20210A homozygous carriers and combined defects). Compared with group O, AB blood group was associated with increased risk of VT: hazard ratio (HR)=3.8 (2.0-7.2). The effect of blood group A and B was milder (HR=1.6 [1.1-2.5] and 1.8 [1.0-3.3], respectively). An increased risk of VT was observed with increasing levels of von Willebrand factor and factor VIII plasma levels (HR=2.96 [1.92-4.56] and HR=2.60 [1.92-4.56] for third versus first tertile of von Willebrand factor and factor VIII plasma levels, respectively). In multivariate analysis, AB group (HR=2.3 [1.1-4.8]), high-risk thrombophilia (HR=2.8 [1.6-4.6]), and high von Willebrand factor levels (HR=2.3 [1.3-4.0]) were significantly associated with increased risk of VT. The risk of VT in individuals with high-risk thrombophilia and AB group was 14.4× higher than in those without thrombophilia and O group (5.0-41.4). ABO blood group modifies the risk of VT in families with hereditary thrombophilia. Phenotyping of the ABO blood group should be performed to better assess the risk of VT in asymptomatic individuals from thrombophilic families.
    Arteriosclerosis Thrombosis and Vascular Biology 05/2012; 32(8):2021-8. · 6.34 Impact Factor
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    ABSTRACT: Prostate cancer is an important disease in terms of economic implications because of its increasing incidence and health care costs. We assessed the direct costs of the clinical management of prostate cancer in France. A retrospective study based on population-based data was carried out. Eight hundred and seventy-nine cases of prostate cancer diagnosed in five departments were included in a 5-year follow-up study. The economic analysis adopted the health-care payer's perspective and took into account only the direct costs. The mean cost of managing patients was estimated at euro12,731. It is composed of 49 to 82% of initial treatments according to the therapeutic strategy. The follow-up constituted between 3 and 11%, the costs of treatments for side effects between 1 and 3% and the travel cost between 3 and 7%. Cumulative total costs over 5 years for each treatment group showed variation in costs. Costs were highest for patients who were treated with external-beam radiotherapy and lowest for those with watchful waiting. The cost burden of prostate cancer is high and varies according to the treatment type. This study yielded a cost analysis of the different management practices of patients with prostate cancer.
    The European Journal of Health Economics 08/2011; 12(4):363-71. · 2.10 Impact Factor
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    ABSTRACT: Poor response to both aspirin and clopidogrel (dual poor responsiveness [DPR]) is a major risk factor for recurrent ischemic events. The aim of this study was to identify factors associated with DPR, defined with specific tests, and derive a predictive clinical score. We studied 771 consecutive stable cardiovascular patients treated with aspirin (n = 223), clopidogrel (n = 111), or both drugs (n = 37). Aspirin responsiveness was evaluated by serum thromboxane (Tx)B₂ assay, and clopidogrel responsiveness by calculating the platelet reactivity index (PRI) on the basis of the phosphorylation status of the vasodilator phosphoprotein. The analysis was focused on patients treated with both drugs, and on independent predictors of DPR. Among patients on dual therapy, there was no relevant correlation between TxB₂ levels and PRI values (r = 0.11). Sixty-seven patients (15.4%) had DPR. Diabetes [odds ratio (OR) 1.89, 95% confidence interval (CI) 1.06-3.39], high body weight (> 86 kg vs. < 77 kg, OR 4.74, 95% CI 2.49-9.73), low aspirin dose (75-81 mg vs. ≥ 160 mg, OR 0.12, 95% CI 0.09-0.93) and high C-reactive protein (CRP) level (> 1.6 mg L⁻¹ vs. < 0.6 mg L⁻¹, OR 3.66, 95% CI 1.74-8.72) were independently associated with DPR, via increased TxB(2) levels, increased PRI, or both. These associations with TxB₂ and PRI were reproduced across the whole population. With use of a factor-weighed score (c-index = 0.74), the predicted prevalence of DPR was 57% in the highest strata of the score as compared with < 4% for the lowest strata. Diabetes, body weight, the aspirin dose and CRP levels are readily available independent predictors of DPR, and some are potential targets for reducing its prevalence.
    Journal of Thrombosis and Haemostasis 12/2010; 8(12):2614-23. · 6.08 Impact Factor
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    ABSTRACT: Exposed to a common environment, the IgE-mediated immune response differs, for instance, among sensitized subjects, some of them reacting toward one allergen (monosensitized) whereas others are sensitized to a wide array of allergens (polysensitized). However, a better phenotypic characterization is needed for epidemiologic studies. Using the data collected during the ECRHS I (European Community Respiratory Health Survey), several assessments of skin prick tests and serum-specific IgE to identify mono- and polysensitized patients were compared. Subjects took part in the ECRHS-I. The CAP-System was used for serum allergen-specific IgE, and allergen-coated Phazet was used for prick tests. Four allergens (Dermatophagoides pteronyssinus, cat, timothy grass, and Cladosporium) were measured using IgE and nine (the same ones plus olive pollen, birch, Alternaria, Parietaria, and ragweed) were skin tested. One to two local allergens were also tested, depending on countries. Prevalence of sensitization in 11,355 subjects (34.0 [27.9-40.1] years, 49.9% men) ranged from 32.3% (four specific IgE, 19.3% mono- and 13.0% polysensitized) to 41.8% (four specific IgE combined to nine prick tests, 19.6% mono- and 22.2% polysensitized). Concordance between four specific IgE and four prick tests was weak (weighted κ 0.65 [0.64-0.66]). Concordance between seven and nine prick tests was high (weighted κ 0.99 [0.98-1.00]). Local allergens induced small changes in the prevalence of sensitization, and reclassified some subjects from mono- to polysensitized. Skin tests or serum-specific IgE may be chosen to identify allergenic sensitivity, mono- and polysensitized subjects without being strictly interchangeable.
    Annals of epidemiology 11/2010; 20(11):797-803. · 2.95 Impact Factor
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    ABSTRACT: The prothrombin (PT) G20210A gene mutation is a common risk factor for venous thrombosis (VT), which is mainly mediated through an increase in factor II (FII) plasma levels. High FII plasma levels may act through an increase in endogenous thrombin potential (ETP) a key step in hemostasis and thrombosis. While FII may be the main contributor to ETP in PT G20210A carriers, the knowledge of other environmental or genetic factors influencing ETP may help to better identify those at risk of VT. ETP was determined in 472 non-carriers of PT G20210A (PT-) and in 325 unrelated carriers of PT G20210A (PT+) with (symptomatic n = 158) or without (asymptomatic, n = 167) a history of VT. All PT+ were heterozygous and free of other thrombophilic defects. ETP was higher in asymptomatic PT+ than in PT- (2038 +/- 371 vs. 1616 +/- 267 nmol L(-1) min; P < 0.0001). ETP was significantly higher in symptomatic PT+ than in controls PT+ (2129 +/- 430 vs. 2038 +/- 371 nmol L(-1) min; P = 0.01). Multivariate analyses evidenced the importance of FII and fibrinogen plasma levels in determining ETP. After taking these variables into account, a personal history of VT remained associated with ETP in PT+ carriers. Moreover, PTG20210A still contributes to ETP after consideration of FII levels. In conclusion, the increase in ETP observed in carriers is not entirely explained by higher FII or fibrinogen plasma levels but also by the history of VT.
    Journal of Thrombosis and Haemostasis 05/2010; 8(5):942-9. · 6.08 Impact Factor
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    ABSTRACT: Background Residual platelet reactivity (RPR) has been shown to be related to adverse cardiovascular events. However, assessment of residual platelet reactivity was often evaluated in heterogeneous populations including both patients with stable disease and acute coronary syndrome. Objectives We aim to delineate determinants of RPR in a cohort of stable cardiovascular patients. Methods We included 750 stable cardiovascular patients treated for at least one month with aspirin (n=213), clopidogrel (n=107) or both (n=425). We evaluated RPR using collagen platelet aggregation (CPA), collagen being a stimulus not directly involved in the specific pathways of aspirin and clopidogrel. Results Mean age was 65±12 years, 76% were male; the mean duration of the CV disease was 1.6 years. CPA ranged from 6% to 96% in our population. CPA was of 41+/-16, 61+/-14 and 28+/-15% in aspirin, clopidogrel and dual treatment groups, respectively (P<0.001). In univariate analysis of relevant biological and clinical parameters, antiplatelet drug treatment pattern (P<0.001), diabetes (P=0.006), hypertension (P=0.01) and a pain-free walking distance < 200m (P=0.02) were associated with CPA. Multivariate analysis showed that antiplatelet drug treatment pattern (P<0.0001) and diabetes (P=0.0007) were independent factors associated with CPA. Conclusion Aspirin had a more pronounced effect on CPA than clopidogrel in stable cardiovascular patients. Even after adjustment for antiplatelet drug pattern, diabetes remains an independent factor associated with CPA. These results give new insight into the controversy about the beneficial effect of antiplatelet drugs in this particular group of patients
    Archives of Cardiovascular Diseases Supplements 01/2010; 2(1):10-10.
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    ABSTRACT: A low response to clopidogrel has been associated with an increased risk of stent thrombosis. However, the definition of a nonresponse to clopidogrel remains controversial, and different tests have been used to assess the clopidogrel response. The present study was designed to assess the predictive value of adenosine diphosphate (ADP)-induced platelet aggregation (ADP-Ag) and the Platelet Reactivity Index of vasodilator-stimulated phosphoprotein for the occurrence of stent thrombosis in patients admitted for non-ST-elevation acute coronary syndrome undergoing percutaneous coronary intervention. A total of 598 consecutive patients with non-ST-elevation acute coronary syndrome undergoing coronary stenting were prospectively included. They received 600 mg of clopidogrel >or=12 hours before percutaneous coronary intervention. Acute or subacute definite or probable stent thrombosis occurred in 11 patients (1.8%). These patients had significantly greater ADP-Ag compared to patients free of stent thrombosis (68 +/- 14% vs 56 +/- 19%, p = 0.002) but only a trend toward a greater Platelet Reactivity Index of vasodilator-stimulated phosphoprotein (62 +/- 14% vs 53 +/- 23%, p = 0.19). The construction of receiver operating characteristic curves to examine the most predictive value of ADP-Ag for stent thrombosis gave a threshold of ADP-Ag of >67% to identify low responders. These patients were at a greater risk of stent thrombosis than the clopidogrel responders (4.3% vs 0.8%, odds ratio 5.8, 95% confidence interval 1.9 to 24.6, p = 0.003). In conclusion, in patients with non-ST-elevation acute coronary syndrome undergoing percutaneous coronary intervention, ADP-Ag is a good parameter to identify clopidogrel nonresponders who are at increased risk of stent thrombosis, with a cutoff value of ADP-Ag of >67%.
    The American journal of cardiology 10/2009; 104(8):1078-82. · 3.58 Impact Factor
  • Revue De Medecine Interne - REV MED INTERNE. 01/2009; 30.
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    ABSTRACT: Objectives:  Cost-of-illness (COI) studies estimate the overall economic burden of a specific disease, rather than simply treatment-related costs. While having been criticized for not allowing resource prioritization, COI studies can provide useful guidance, so long as they adhere to accepted methodology. Prostate cancer is an important disease in terms of economic implications because of its increasing incidence and health-care costs and therefore provides a relevant example with which to review COI study methodologies. The aim of this study was to review published COI studies on prostate cancer to analyze the methods used.Methods:  First, we provide a general description of the COI method. COI studies relating to prostate cancer were then systematically reviewed, focussing on an analysis of the different methods used.Results:  The methods, data sources, and estimated cost categories in each study varied widely. The review showed that COI studies adopted significantly different approaches to estimate the costs of prostate cancer, reflecting a lack of consensus on the methodology of COI studies in this area.Conclusion:  To increase its credibility, closer agreement among researchers on the methodological principles of the COI studies would be desirable.
    Value in Health 08/2008; 11(5):878 - 885. · 2.19 Impact Factor
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    ABSTRACT: Cost and effectiveness are usually modeled according to one studied event or one health state with parametric or non-parametric methods. In this paper, we propose an original method for assessing total costs while incorporating the dynamics of change in the health status of patients. A semi-Markov model in which the distributions of sojourn times are explicitly defined is developed. The hazard function of sojourn times is modeled by Weibull distributions specific to each transition. A vector of covariates is incorporated into the hazard function of each transition. From a regression model for costs, a cumulative cost function is derived. An estimation of the mean cost per patient in each state defined in the semi-Markov model could thus be made, and this enables us to identify the determinants of direct costs. The results of incremental net benefit (INB) are assessed using the bootstrap method. A cost-effectiveness analysis is performed in order to compare two strategies of follow-up in the colorectal cancer study. Two hundred and forty patients were enrolled in this study. Three health states are defined for patients with curative resection of colorectal cancer: alive without relapse, alive with relapse, and dead. The mean survival is 4.35 and 4.12 years, respectively, in the standard and moderate follow-up groups. We show that mean cost differs significantly by follow-up strategy and Dukes stage. Finally, the INB is assessed and this indicates that neither of the strategies compared was more cost-effective than the other.
    Statistics in Medicine 01/2008; 26(30):5557-71. · 2.04 Impact Factor
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    ABSTRACT: Informative censoring in survival analysis and application to asthma
    Far East Journal of Theoritical Statistics. 01/2006; 2(19):203-217.
  • Thrombosis Research 131:S74. · 3.13 Impact Factor

Publication Stats

109 Citations
51.38 Total Impact Points


  • 2010–2012
    • Université de Nîmes
      Nismes, Languedoc-Roussillon, France
  • 2008–2011
    • Institut Universitaire de France
      Lutetia Parisorum, Île-de-France, France
    • French Institute of Health and Medical Research
      Lutetia Parisorum, Île-de-France, France