Publications by authors named "Mathilde Lefort"

8 Publications

  • Page 1 of 1

The effectiveness of natalizumab vs fingolimod-A comparison of international registry studies.

Mult Scler Relat Disord 2021 May 8;53:103012. Epub 2021 May 8.

KTU Medical Faculty Farabi Hospital, Trabzon, Turkey.

Background: Natalizumab and fingolimod were the first preparations recommended for disease breakthrough in priorly treated relapsing-remitting multiple sclerosis. Of three published head-to-head studies two showed that natalizumab is the more effective to prevent relapses and EDSS worsening.

Methods: By re-analyzing original published results from MSBase, France, and Denmark using uniform methodologies, we aimed at identifying the effects of differences in methodology, in the MS-populations, and at re-evaluating the differences in effectiveness between the two drugs. We gained access to copies of the individual amended databases and pooled all data. We used uniform inclusion/exclusion criteria and statistical methods with Inverse Probability Treatment Weighting.

Results: The pooled analyses comprised 968 natalizumab- and 1479 fingolimod treated patients. The on-treatment natalizumab/fingolimod relapse rate ratio was 0.77 (p=0.004). The hazard ratio (HR) for a first relapse was 0.82 (p=0.030), and the HR for sustained EDSS improvement was 1.4 (p=0.009). There were modest differences between each of the original published studies and the replication study, but the conclusions of the three original studies remained unchanged: in two of them natalizumab was more effective, but in the third there was no difference between natalizumab and fingolimod.

Conclusion: The results were largely invariant to the epidemiological and statistical methods but differed between the MS populations. Generally, the advantage of natalizumab was confirmed.
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May 2021

Long-term effect of first-line injectable multiple sclerosis treatments: Input of a time-dependent propensity score.

Pharmacoepidemiol Drug Saf 2020 12 11;29(12):1680-1688. Epub 2020 Nov 11.

Pharmaco-epidemiology and health Services Research Department, Rennes University, EHESP, REPERES - EA 7449, Rennes, France.

Purpose: The long-term effect of beta-interferon and glatiramer acetate on multiple sclerosis (MS) disability progression has resulted in controversial results, probably due to a lack of appropriate control of biases as raised in observational studies. In particular, the time of the therapeutic decision is difficult to define when the controls are not treated.

Methods: This retrospective observational study was based on a series of patients from the MS expert center in Rennes, France. We used a time-dependent propensity score defined as the linear predictor of a Cox model estimating the hazard of being treated at each time from MS onset. The matching procedure resulted in two groups: patients matched as treated and as not yet treated. The restricted mean times (RMST) to reach a moderate level of disability or worsening of the disability were compared between the two groups in an intention-to-treat analysis.

Results: Of the 2383 patients included in the study, 556 were matched as treated. The matching procedure provided a good balance of both the time-fixed and the time-dependent covariates. A slight difference was observed for the time to reach a moderate level of disability, in favor of the "not yet treated" group (difference in the RMST: -0.62 [-0.91; -0.33]) while no difference was found in terms of worsening of the disability (-0.03 [-0.24; 0.33]).

Conclusion: This unexpected result is probably due to unmeasured confounders. However, this time-dependent PS warrants consideration in long-term effectiveness studies.
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December 2020

Metastatic Clear-cell Renal Cell Carcinoma With a Long-term Response to Sunitinib: A Distinct Phenotype Independently Associated With Low PD-L1 Expression.

Clin Genitourin Cancer 2019 06 4;17(3):169-176.e1. Epub 2019 Feb 4.

Service d'Anatomie et Cytologie Pathologiques, Université de Rennes 1, Université Bretagne Loire, Rennes, France; Unité Mixte de Recherche 6290-Institut de Génétique et Développement de Rennes, Rennes, France.

Background: Long-term responders (LTRs) are defined by at least 18 months of response to sunitinib in metastatic clear-cell renal cell carcinoma (ccRCC). Well-described by clinical studies, the phenotype of these tumors has never been explored.

Patients And Methods: In a retrospective and multicenter study, 90 ccRCCs of patients with metastatic disease were analyzed. Immunohistochemistry (carbonic anhydrase IX, vascular endothelial growth factor, c-MET, programmed death-ligand 1 [PD-L1], and PD-1) and VHL status were performed. Progression-free survival and overall survival were calculated from sunitinib introduction and from progression. LTRs and their corresponding tumors were compared with others using univariate and multivariate analysis.

Results: Twenty-eight patients were LTRs. They had a median progression-free survival of 28 months versus 4 months for other patients (P < .001). Similarly, LTRs had a median overall survival of 49 months versus 14 months (P < .001), even from progression (median, 21 vs. 7 months; P = .029). They were associated with a favorable or intermediate risk (International Metastatic Renal Cell Carcinoma Database Consortium model) (P = .007) and less liver metastasis (P = .036). They experienced more frequent complete or partial responses at the first radiologic evaluation (P = .035). The corresponding ccRCCs were associated with less nucleolar International Society for Urological Pathology grade 4 (P = .037) and hilar fat infiltration (P = .006). They were also associated with low PD-L1 expression (P = .02). Only the International Metastatic Renal Cell Carcinoma Database Consortium model and PD-L1 expression remained significant after multivariate analysis (P = .014 and P = .029, respectively).

Conclusion: Primary tumor characteristics of LTRs were studied for the first time and demonstrated a different phenotype. Interestingly, they were characterized by low expression of PD-L1, suggesting a potentially lower impact of targeted immunotherapy in these patients.
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June 2019

Sex differences in adherence to antihypertensive treatment in patients aged above 55: The French League Against Hypertension Survey (FLAHS).

J Clin Hypertens (Greenwich) 2018 10 21;20(10):1496-1503. Epub 2018 Sep 21.

Comité Français de Lutte Contre l'Hypertension Artérielle (CFLHTA), Paris, France.

Despite the availability of efficient therapies to reduce the risk of cardiovascular complications, poor adherence to antihypertensive (anti-HTN) drugs is frequent, especially during the first year of treatment and among uncontrolled/resistant hypertensive patients. The aim of the study was to identify factors associated with adherence to anti-HTN treatment and to examine whether they differ across sex. A total of 2743 treated hypertensive participants to the cross-sectional Metascope survey (France, 2015) aged 55 years or more were included. The authors measured adherence to anti-HTN treatment using the 6-item Girerd compliance test. Variations in adherence were examined using the Rao-Scott statistics and Poisson regression. Overall, 63.6% of participants were adherent to anti-HTN treatment. Adherence was more frequent among women than men (69% vs 58%, P < 10 ). For both sexes, level of adherence was positively associated with age (P < 10 ), but inversely associated with number of anti-HTN tablets, number of tablets taken for metabolic diseases, history of cardiovascular diseases, number of other chronic diseases (all P < 10 ). The inverse relationship between adherence and the number of anti-HTN tablets significantly differed between sexes (P < 10 ): Adherence decreased sharply when taking two or more anti-HTN tablets in men, whereas the decrease in women was only observed when taking three or more anti-HTN tablets. This study suggests that adherence to anti-HTN treatment is higher among women, decreases with the number of tablets prescribed, and differentially so across sex. Reducing the number of tablets for anti-HTN treatment may improve adherence, especially among men and patients with multiple comorbidities.
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October 2018

Categorical state sequence analysis and regression tree to identify determinants of care trajectory in chronic disease: Example of end-stage renal disease.

Stat Methods Med Res 2019 06 9;28(6):1731-1740. Epub 2018 May 9.

1 Univ Rennes, EHESP, REPERES (Recherche en Pharmaco-épidémiologie et Recours aux Soins) - EA 7449, Rennes, France.

Background: Patients with chronic diseases, like patients with end-stage renal disease (ESRD), have long history of care driven by multiple determinants (medical, social, economic, etc.). Although in most epidemiological studies, analyses of health care determinants are computed on single health care events using classical multivariate statistical regression methods. Only few studies have integrated the concept of treatment trajectories as a whole and studied their determinants.

Methods: All 18- to 80-year-old incident ESRD patients who started dialysis in Ile-de-France or Bretagne between 2006 and 2009 and could be followed for a period of 48 months after initiation of a renal replacement therapy were included ( = 5568). Their care trajectories were defined as categorical state sequences. Associations between patients' characteristics and care trajectories were assessed using a regression tree model together with a discrepancy analysis.

Results: On average, each patient experienced 1.56 different renal replacement therapies (min = 1; max = 5) during the 48 months of follow-up. About 55% of patients never changed treatment and only 1% tried three or more renal replacement therapy modalities. Twelve homogeneous care trajectory groups were identified. Covariates explained 12% of the discrepancy between groups, particularly age, regions and initiation of hemodialysis with a catheter.

Conclusions: Regression tree analysis of categorical state sequence highlighted geographical disparities in the care trajectory of French patients with ESRD that cannot be observed when focusing on a single outcome, such as survival. This method is an original tool to visualize and characterize care trajectories, notably in the context of chronic condition like ESRD.
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June 2019

Hilar fat infiltration: A new prognostic factor in metastatic clear cell renal cell carcinoma with first-line sunitinib treatment.

Urol Oncol 2017 10 12;35(10):603.e7-603.e14. Epub 2017 Jun 12.

Service d'Anatomie et Cytologie Pathologiques, Université de Rennes 1, Université Bretagne Loire, Rennes, France; UMR 6290, IGDR, Rennes, France.

Introduction: The selection of patients with metastatic clear cell renal cell carcinoma (ccRCC) who may benefit from targeted tyrosine kinase inhibitors has been a challenge, even more so now with the advent of new therapies. Hilar fat infiltration (HFI) is a validated prognostic factor in nonmetastatic ccRCC (TNM 2009 staging system) but has never been studied in metastatic patients. We aimed to assess its phenotype and prognostic effect in patients with metastatic ccRCC treated with first-line sunitinib.

Materials And Methods: In a multicentric study, we retrospectively included 90 patients and studied the corresponding ccRCC at the pathological, immunohistochemical, and molecular levels. Patient and tumor characteristics were compared using univariate and multivariate analysis. All the features were then studied by Cox models for prognostic effect.

Results: HFI was found in 42 patients (46.7%), who had worse prognosis (Heng criteria) (P = 0.003), liver metastases (P = 0.036), and progressive diseases at first radiological evaluation (P = 0.024). The corresponding ccRCC was associated with poor pathological prognostic factors that are well known in nonmetastatic ccRCC. For these patients, median progression-free survival was 4 months vs. 13 months (P = 0.02), and median overall survival was 14 months vs. 29 months (P = 0.006). In a multivariate Cox model integrating all the variables, only poor prognosis, according to the Heng criteria and HFI, remained independently associated with both progression-free survival and overall survival.

Conclusion: HFI was demonstrated for the first time to be an independent poor prognostic factor. Its potential role in predicting resistance to antiangiogenic therapy warrants further investigation.
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October 2017

[Glioblastoma and nursing care in neurosurgery].

Mathilde Lefort

Rev Infirm 2017 Feb;66(228):26-28

Hôpital d'instruction des armées Percy, 101 avenue Henri Barbusse, BP 406, 92141 Clamart Cedex, France. Electronic address:

Nurses in neurosurgical departments play a critical role as they are involved in the first stages of the care pathway of patients with glioblastoma. Indeed, surgery enables a definitive histopathological diagnosis to be established and the size of the tumour to be significantly reduced, thereby improving the prognosis.
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February 2017

Facilitating access to the renal transplant waiting list does not increase the number of transplantations: comparative study of two French regions.

Clin Kidney J 2016 Dec 9;9(6):849-857. Epub 2016 Sep 9.

EHESP, Sorbonne Paris Cité, METIS, Avenue du professeur Léon Bernard, 35043 Rennes, France.

Background: In France, there are important regional disparities of access to the renal transplant waiting list and transplantation. Our objectives were to compare the characteristics of patients with end-stage renal disease (ESRD) of two French regions (Ile-de-France and Bretagne) and to identify determinants of access to the waiting list and subsequent transplantation, with a focus on temporary inactive status (TIS) periods.

Methods: All 18-80-year-old incident patients who started dialysis in Ile-de-France or Bretagne between 2006 and 2009 were included ( = 6160). Associations between patients' characteristics and placement on the waiting list or transplantation were assessed using a Fine and Gray model to take into account the competing risk of death and living donor transplantation.

Results: At the end of the follow-up (31 December 2013), more patients had undergone transplantation in Bretagne than in Ile-de-France (30 versus 27%), although the percentage of waitlisted patients was higher in Ile-de-France than in Bretagne (47 versus 33%). More patients were on TIS and with a longer median TIS duration in Ile-de-France. Independent of age and clinical characteristics, patients in Bretagne were less likely to be waitlisted than those in Ile-de-France [subdistribution hazard ratio 0.77 (95% confidence interval 0.7-0.9)]. After waitlisting, patients in Bretagne were four times more likely to be transplanted.

Conclusions: Our study highlights clinical practice differences in Bretagne and Ile-de-France and shows that facilitating access to the waiting list is not sufficient to improve access to renal transplantation, which also depends on organ availability.
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December 2016