David Hajage | Université Paris Diderot (original) (raw)
Papers by David Hajage
PLoS ONE, 2011
Background: Adjuvant! Online is a web-based application designed to provide 10 years survival pro... more Background: Adjuvant! Online is a web-based application designed to provide 10 years survival probability of patients with breast cancer. Several predictors have not been assessed in the original Adjuvant! Online study. We provide the validation of Adjuvant! Online algorithm on two breast cancer datasets, and we determined whether the accuracy of Adjuvant! Online is improved with other well-known prognostic factors.
Journal of Clinical Epidemiology, 2015
Control treatments in randomized controlled trials (RCTs) should not deliberately disadvantage pa... more Control treatments in randomized controlled trials (RCTs) should not deliberately disadvantage patients. To compare (a) willingness to include versus (b) willingness to prescribe control treatment among physicians randomized to assess, respectively, either (a) enrollment in a trial or (b) appropriateness of control treatment in a care context for the same fictional patient. Physicians were authors of articles about rheumatoid arthritis (RA), involved in RA patient care and used to enrolling patients in trials. Willingness to give control treatment: trial enrollment or control-treatment appropriateness in care context. We derived 3 case vignettes of fictional standard eligible patients for each of 30 RCTs assessing biologics in RA. Physicians were randomly allocated to the "trial" or "care" arm. For each of the 90 fictional patients, physicians assigned to the trial arm were asked if they would enroll the patient in the RCT the patient was derived from. For the same 90 fictional patients, physicians assigned to the care arm were asked if the control treatment of the RCT was appropriate in a context of usual care. Of the 1,779 physicians invited to participate, 151 were randomized. Half of the fictional patients (41/90; 45% [95%CI 37-53%]) would be enrolled in the RCT even though the control-arm treatment of the RCT was not considered appropriate for them in the context of care. This rate differed by type of comparator (55% for non-head-to-head RCTs vs 6% for head-to-head RCTs; adjusted OR (aOR) 23.9 [95%CI 5.5-92.7]) and duration of trial control treatment (56% for ≤ 24 weeks and 15% for > 24 weeks; aOR 10.7 [95%CI 2.8-63.9]) but not patient RA activity (aOR 2.5 [95%CI 1.0-6.6]). Fictional patients, RA only. Control treatments in RCTs of biologics in RA are often deemed not acceptable in the context of usual care, especially those for non-head-to-head RCTs. These findings raise ethical concerns and challenge the choice of the comparator in RCTs.
International Journal of Antimicrobial Agents, 2015
The epidemiology of multidrug-resistant bacteria (MDRB) has changed significantly in European hea... more The epidemiology of multidrug-resistant bacteria (MDRB) has changed significantly in European healthcare settings, with a decrease in frequency of meticillin-resistant Staphylococcus aureus and an increase in extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae. Little is known about the effects of these changes on ventilator-associated pneumonia (VAP). A retrospective 5-year trend analysis of ICU antibiotic consumption and resistance in bacteria causing VAP was undertaken. Poisson regression analysis between complete microbiological data and antibiotic consumption was performed. In total, 252 episodes of VAP in 184 patients were identified between 2007 and 2011, from which 364 causal bacteria were isolated. Enterobacteriaceae isolation rates increased significantly over this period [from 6.64 to 10.52 isolates/1000 patient-days; P=0.006], mostly due to an increase in AmpC-producing Enterobacteriaceae (APE) (2.85-4.51 isolates/1000 patient-days; P=0.013), whereas the number of episodes due to S. aureus and Pseudomonas aeruginosa remained stable. A positive association was found between the increase in APE infections and an increase in past-year antibiotic consumption: amoxicillin/clavulanic acid (P=0.003), ceftazidime and cefepime (P=0.007), carbapenems (P=0.002), fluoroquinolones (P=0.012), macrolides (P=0.002) and imidazoles (P=0.004). No such association was found for the emergence of resistance in P. aeruginosa. These results indicate a change in the epidemiology of VAP, with Enterobacteriaceae exceeding P. aeruginosa and S. aureus. Moreover, a positive correlation was observed between antibiotic consumption and the incidence of potentially MDRB such as APE. No such correlation was found for ESBL-producing Escherichia coli and antibiotic-resistant P. aeruginosa.
Néphrologie & Thérapeutique, 2011
un accident ischémique transitoire (23 cas), une protéinurie > 0,5gl (24 cas), une claudication i... more un accident ischémique transitoire (23 cas), une protéinurie > 0,5gl (24 cas), une claudication intermittente : (87 cas), une HTA grade I (88 cas), grade II (47 cas), et grade III (5 cas), 3 FDR/AOC sont retrouvés chez les diabétiques (46 cas) ; une maladie cardiovasculaire (MCV) et atteinte rénale ). La moitié des patients suivis avaient une insuffisance rénale chronique (IRC) <60 mL/minute. Les mesures hygiéno-diététique (MHD) sont appliquées chez 186 patients, la bithérapie anti-HTA : (67 cas), trithérapie : (98 cas), quadrithérapie : (21 cas), statines : (126 cas), principal facteur de résistance de l'HTA : la non observance du Traitement. Discussion.-Plus de 75 % de nos patients ont un RCVG élevé (soit 140 cas), Les PA cibles selon l'OMS, atteintes chez moins de 24 % (soit 46 cas), L'obtention d'un équilibre tentionnel adéquat chez des malades tarés, présentant plus de 3 FDR est difficile et impose le recours à une poly-médication, souvent astreignante [1]. Conclusion.-L'HTA est un problème de santé majeure de santé publique [1]. La prise en charge du patient hypertendu doit reposer à la fois sur les valeurs de la pression artérielle (PA) et sur le niveau de RCVG, l'implication et la sensibilisation du malade occupe une place prépondérante dans la lutte contre les RCVG [1]. Référence [1] Agence nationale d'accréditation et d'évaluation en santé. Introduction.-Objectifs.-Chez les patients admis en réanimation pour insuffisance rénale aiguë obstructive (IRAO), déterminer les facteurs prédisant la survenue d'un syndrome de levée d'obstacle (SLO) après dérivation des urines, ou la persistance d'une insuffisance rénale chronique (IRC) sévère. Patients et méthodes.-Étude rétrospective de patients admis pour IRAO dans deux services de réanimation de 1998 à 2010. Définition du SLO : polyurie > 4L/j après dérivation des urines. Analyses uniet multivariées pour rechercher : -des facteurs prédisant la survenue du SLO ; -des facteurs prédisant la persistance d'une IRC sévère (eDFG < 30 mL/minute/1,73m2 selon le MDRD) à trois mois chez les patients indemnes d'IRC sévère avant l'épisode d'IRAO. Les résultats sont présentés en médiane (extrêmes) ou en pourcentage. Résultats.-Nous avons étudié 62 patients (âge : 70 [38-90] ans, urée plasmatique : 39 [8-166] mmo/L, créatininémie 866 [247-3119] mol/L, globe vésical 52 %). L'obstruction était due à un cancer dans 50 % des cas, un adénome de prostate dans 21 %. Un SLO est survenu dans 63 % des cas (diurèse des 24 premières heures : 7,0 [4,0-15,0] L). Les facteurs prédisant la survenue d'un SLO en analyse univariée puis multivariée étaient : l'élévation de la bicarbonatémie (odds-ratio [OR] 1,36, 95 % CI [1,13-1,65], p < 0,001), l'élévation de la créatininémie (OR 1,002, 95 % CI [1,001-1,004] p = 0,004) et la présence d'un globe vésical (OR 6,96, 95 % CI [1,34-36,23], p . Le score dérivé du modèle multivarié, calculé comme 0,31 × bicarbonatémie (mmol/L) + 0,002 × créatininémie (mol/L) + 1,95 si globe -7,15 prédisait la survenue d'un SLO avec une aire sous la courbe ROC de 0,85 (95 % CI : 0,749-0,951). Un score supérieur à 0 prédisait la survenue d'un SLO avec une sensibilité de 91 % et une spécificité (Sp) de 60 %. Parmi les 34 patients indemnes d'IRC sévère au préalable et pour lesquels un suivi à trois mois était disponible, une IRC terminale persistait dans 6 % des cas seulement, mais une IRC sévère persistait dans 21 % des cas. Les facteurs prédisant la persistance d'une IRC sévère en analyse univariée étaient : la diminution de l'hémoglobine sanguine (p < 0,001) et de la bicarbon (p = 0,03), une faible diurèse après dérivation (p = 0,03) et l'absence de SLO (p = 0,04), et une natriurèse plus élevée (p = 0,03). Une diurèse > 7,0 L/24 heures après dérivation prédisait l'absence d'IRC sévère à trois mois avec une Sp de 100 %. Une diurèse < 3,0 L prédisait la persistance d'une IRC sévère avec une Sp de 88 %. Les seuils d'hémoglobine sanguine et de bicarbonatémie les plus performants étaient respectivement de 10 g/dL et de 15 mm. Les variables d'imagerie (épaisseur du parenchyme rénal . . .) manquaient trop souvent pour être testées. Une analyse multivariée n'a pu être effectuée (taille de l'échantillon).
Journal of critical care, 2014
Renal replacement therapy (RRT) is a major supportive treatment of acute kidney injury (AKI) in i... more Renal replacement therapy (RRT) is a major supportive treatment of acute kidney injury (AKI) in intensive care unit (ICU), but the timing of its initiation remains open to debate. We retrospectively analyzed ICU patients who had AKI associated with at least one usual RRT criteria: serum creatinine concentration greater than 300 μmol/L, serum urea concentration greater than 25 mmol/L, serum potassium concentration greater than 6.5 mmol/L, severe metabolic acidosis (arterial blood pH<7.2), oliguria (urine output<135 mL/8 hours or <400 mL/24 hours), overload pulmonary edema. To estimate the risk of death associated with RRT adjusted for risk factors, we performed a marginal structural Cox model with inverse-probability-of-treatment-weighted estimator. Among 4173 patients admitted to the ICU, 203 patients fulfilled potential RRT criteria. Ninety-one patients (44.8%) received RRT and 112 (55.2%) did not. Non-RRT and RRT patients differed in terms of severity of illness: Simplifi...
BMC proceedings, 2007
In the present paper, we used the North American Rheumatoid Arthritis Consortium data provided fo... more In the present paper, we used the North American Rheumatoid Arthritis Consortium data provided for Genetic Analysis Workshop 15 Problem 2 to: 1) estimate the penetrances of PTPN22 and HLA-DRB1 and, 2) test the selected model of PTPN22 conditional on the rheumatoid factor status. To achieve these aims, we used the marker association segregation chi-square method, fitting simultaneously both genotype frequency and identical by descent distributions in a sample of 3690 White individuals from 604 nuclear families. A co-dominant model fitted the rs2476601 (R620W) single-nucleotide polymorphism (SNP) of the PTPN22 gene well, whereas a lack of fit for all models was observed for the HLA-DRB1 locus. Testing genetic models of rheumatoid arthritis that include the PTPN22 SNP in addition to the HLA-DRB1 locus did not affect the results, nor did subgroup analysis of PTPN22 conditional on the rheumatoid factor status. In conclusion, PTPN22 R620W SNP is a risk factor for rheumatoid arthritis. The...
Thrombosis Research, 2014
Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy (TMA), related to a sev... more Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy (TMA), related to a severe functional deficiency of ADAMTS13 activity (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;10% of normal). ADAMTS13 activity is thus crucial to confirm the clinical suspicion of TTP, to distinguish it from other TMAs, and to perform the follow-up of TTP patients. We compared the performance of the commercial chromogenic assay Technozym ADAMTS13 Activity ELISA (chromogenic VWF73 substrate, Chr-VWF73, Technoclone, Vienna, Austria), to that of our in-house FRETS-VWF73 used as reference method. A large group of 247 subjects (30 healthy volunteers and 217 patients with miscellaneaous TMAs) was studied. The lower limit of detection of the Chr-VWF73 was 3%, which is well adapted to the clinically relevant threshold for TTP diagnosis (10%). Our results showed a reasonable agreement between FRETS-VWF73 and Chr-VWF73 assays to distinguish samples with an ADAMTS13 activity &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;10% from those with an ADAMTS13 activity &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;10%. However, Chr-VWF73 assay provided false negative results in ~12% of acute TTP patients. Inversely, the Chr-VWF73 assay globally underestimated ADAMTS13 activity in detectable values ranging from 11 to 100% (with a great variability compared to FRETS-VWF73), which may be a concern for the follow-up of TTP patients in remission. In-house assays developed and performed by expert laboratories remain the reference methods that should be used without limitation to control values provided by commercial assays when needed. Also, the development of an international reference preparation will be crucial to improve standardization.
Obesity Surgery, 2015
Obesity induces cardiovascular alterations, including cardiac hypertrophy, impaired relaxation, a... more Obesity induces cardiovascular alterations, including cardiac hypertrophy, impaired relaxation, and heart rate variability (HRV), which are associated with increased mortality. Gastric bypass surgery (GBP) reduces cardiovascular mortality, but the mechanisms involved are not clearly established. To date, the implication of postsurgical hormonal changes has not been tested. Our aim was to study the relationships between the evolution of cardiovascular functions after GBP and changes in metabolic and hormonal parameters, including glucagon-like peptide-1 (GLP-1) and brain natriuretic peptide (N-terminal pro-brain natriuretic peptide (NT-proBNP)). Echocardiographic parameters, 24-h rhythmic Holter recording, plasma concentrations of GLP-1 before and after a test meal, and fasting NT-proBNP were assessed in 34 patients (M/F 2/32, age 36 ± 11 years, BMI 46 ± 6 kg/m(2)), before and 1 year after GBP. After GBP, excess weight loss was 79 ± 20 %. Blood pressure (BP), heart rate, and left ventricular mass decreased, while HRV and diastolic function (E/A ratio) improved. Plasma concentrations of NT-proBNP and postprandial (PP) GLP-1 increased. Changes in cardiovascular parameters were related to BMI and insulin sensitivity. Furthermore, the decrease in BP was independently associated with the increase of PP GLP-1 level and HRV was positively associated with NT-proBNP concentration after surgery. The increase in endogenous GLP-1 observed after GBP was associated with decreased BP but not with improvement of other cardiovascular parameters, whereas the increase in NT-proBNP, within the physiological range, was associated with improved HRV.
Médecine et Maladies Infectieuses, 2014
Given the increasing frequency of cefotaxime-resistant strains, third-generation cephalosporins (... more Given the increasing frequency of cefotaxime-resistant strains, third-generation cephalosporins (3GC e.g. cefotaxime, ceftriaxone) might not be recommended any longer as empirical antibiotic therapy for community-acquired Gram-negative bacteremia (CA-GNB). We conducted a multicenter prospective descriptive study including patients with CA-GNB. Two hundred and nineteen patients were included. Escherichia coli and Pseudomonas aeruginosa were the most frequently isolated species in 63% (n=138) and 11% (n=24) of the cases, respectively. The prevalence of cefotaxime-resistance reached 18% (n=39) mostly due to intrinsic resistance (27 cases, 12%). The presence of invasive material (P<0.001), the origin of the patient (Paris region or West of France) (P=0.006), and home health care (P<0.001) were variables predicting resistant GNB. The negative predictive value for resistance in patients with invasive material coming from the West of France, or without invasive material and with home health care was 94%. The positive predictive value for patients with invasive material living in Paris, or without invasive material and with home health care only reached 58 and 54%, respectively. Using 3GC for CA-GNB due to cefotaxime-resistant strains was relatively frequent, ESBL-producing Enterobacteriaceae being rarely involved. Our study highlights the role of local epidemiology; before any changes to first-line antibiotic therapy, local epidemiological data should be taken into account.
Breast, 2012
The clinical management of lobular carcinoma in situ lesions remains challenging. Our aim was to ... more The clinical management of lobular carcinoma in situ lesions remains challenging. Our aim was to evaluate the risk of relapse for lobular carcinoma in situ (LCIS) patients, diagnosed on mammography performed for microcalcifications and according to proliferation assessed by Ki67 staining. A series of 47 patient&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s files with LCIS and followed in our institution were retrospectively selected. All patients underwent lumpectomy without radiation therapy. The expression of E-cadherin, estrogen receptor (ER), progesterone receptor (PR), EGFR and Ki67 were determined. Four different classes were then defined with the following criteria: ER+ and Ki67 ≤ 10%; ER+, Ki67 &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;10%; ER-; ER-PR- and EGFR+. Patient&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s mean age was 51.3 yrs. The majority of the lesions were classical LCIS (97%). All cases were E-cadherin either negative (71%) or weak and incomplete (29%). Among the 44 evaluable cases, 34 cases were ER or PR positive with KI67 ≤ 10% (79%), 9 cases ER positive with KI67 &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 10% (21%), 1 case was ER and PR negative and expressed EGFR. At five years, all patients were alive, 1/34 ER positive and Ki67 low experienced a relapse contrasting with 3 out of 9 ER positive and Ki67 high (3 invasive carcinomas including 2 ductal and 1 lobular) (p = 0.0054). In this retrospective study, we observed a higher risk of relapse associated with a high proliferative activity of classical LCIS. If confirmed in larger series, this observation suggests that radiation therapy or hormonotherapy could be discussed for patients with Ki67 high classical LCIS in order to decrease their risk of relapse.
Breast Cancer Research, 2012
Circulating tumor cells (CTC) have been recently proposed as a new dynamic blood marker whose pos... more Circulating tumor cells (CTC) have been recently proposed as a new dynamic blood marker whose positivity at baseline is a prognostic factor and whose changes under treatment are correlated with progression-free survival (PFS) in metastatic breast cancer patients. However, serum marker levels are also used for the same purpose, and no clear comparison has been reported to date. The IC 2006-04 enrolled prospectively 267 metastatic breast cancer patients treated by first line chemotherapy and confirmed that CTC levels are an independent prognostic factor for PFS and overall survival (OS). A secondary pre-planned endpoint was to compare prospectively the positivity rates and the value of CTC (CellSearch®), of serum tumor markers (carcinoembryonic antigen (CEA), cancer antigen 15.3 (CA 15-3), CYFRA 21-1), and of serum non-tumor markers (lactate deshydrogenase (LDH), alkaline phosphatase (ALP)) at baseline and under treatment for PFS prediction, independently from the other known prognostic factors, using univariate analyses and concordance indexes. A total of 90% of the patients had at least one elevated blood marker. Blood markers were correlated with poor performance status, high number of metastatic sites and with each other. In particular, CYFRA 21-1, a marker usually used in lung cancer, was elevated in 65% of patients. A total of 86% of patients had either CA 15-3 and/or CYFRA 21-1 elevated at baseline. Each serum marker was associated, when elevated at baseline, with a significantly shorter PFS. Serum marker changes during treatment, assessed either between baseline and week 3 or between baseline and weeks 6 to 9, were significantly associated with PFS, as reported for CTC. Concordance indexes comparison showed no clear superiority of any of the serum marker or CTC for PFS prediction. For the purpose of PFS prediction by measuring blood marker changes during treatment, currently available blood-derived markers (CTC and serum markers) had globally similar performances. Besides CEA and CA 15-3, CYFRA 21-1 is commonly elevated in metastatic breast cancer and has a strong prognostic value.
SpringerPlus, 2013
The aims of the study were to investigate the factors associated with not having breast reconstru... more The aims of the study were to investigate the factors associated with not having breast reconstruction following mastectomy and to assess patient satisfaction with information on reconstruction. We analysed a historical cohort of 1937 consecutive patients who underwent mastectomy at Institut Curie between January 2004 and February 2007. Their sociodemographic and clinicobiological characteristics were recorded in a prospective database. A questionnaire was sent to 10% of nonreconstructed patients. The proportion of patients with invasive cancer was 82.7%. The rate of nonreconstruction in patients with in situ and invasive cancer was 34.6% and 74.9%, respectively. On multivariate analysis, only employment outside the home was associated with reconstruction in patients with in situ cancer (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). In patients with invasive cancer, employment status (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001) and smoking (p = 0.045) were associated with reconstruction, while age &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 50, ASA score &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;1, radiotherapy (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001) and metastatic status (p = 0.018) were associated with nonreconstruction. For 80% of questionnaire responders, nonreconstruction was a personal choice, mainly for the following reasons: refusal of further surgery, acceptance of body asymmetry, risk of complications and advanced age. Information on reconstruction was entirely unsatisfactory or inadequate for 62% of patients. Better understanding the factors that influence decision of nonreconstruction can help us adapt the information to serve the patient&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s personal needs.
Progrès en urologie : journal de l'Association française d'urologie et de la Société française d'urologie, 2009
Nephron sparing surgery raises the challenge of avoiding chronic haemodialysis for patients havin... more Nephron sparing surgery raises the challenge of avoiding chronic haemodialysis for patients having malignancies on a solitary kidney. The aim of this study was to estimate the long term renal function, survival and risk of recurrence of patients undergoing elective nephron sparing surgery for renal cancer on a solitary kidney. Between January 1975 and December 2002, 37 elective nephron sparing surgery of kidney tumors were performed on 33 patients with a solitary kidney. Surgery was performed without interruption of blood flow. Pre- and postoperative renal function were compared by using a non parametric test of Kruskal and Wallis. Survival rates were estimated by the Kaplan Meier method and the prognostic factors were defined on a multivariate analysis using a Cox model. Mean tumoral diameter was 4.6 cm [1.5-10]. The median follow-up was of 83 months. Three patients died in the postoperative period. The postoperative creatinine clairance was significantly lower than the preoperativ...
Critical Care Medicine, 2014
Tracheal intubation of ICU patients is frequently associated with severe hypoxemia. Although noni... more Tracheal intubation of ICU patients is frequently associated with severe hypoxemia. Although noninvasive ventilation reduces desaturation during intubation of severely hypoxemic patients, it does not allow for per-procedure oxygenation and has not been evaluated in mild-to-moderate hypoxemic patients for whom high-flow nasal cannula oxygen may be an alternative. We sought to compare pre- and per-procedure oxygenation with either a nonrebreathing bag reservoir facemask or a high-flow nasal cannula oxygen during tracheal intubation of ICU patients. Prospective quasi-experimental before-after study (ClinicalTrials.gov: NCT01699880). University hospital medico-surgical ICU. All adult patients requiring tracheal intubation in the ICU were eligible. In the control (before) period, preoxygenation was performed with a nonrebreathing bag reservoir facemask and in the change of practice (after) period, with high-flow nasal cannula oxygen. Primary outcome was median lowest SpO2 during intubation, and secondary outcomes were SpO2 after preoxygenation and number of patients with saturation less than 80%. One hundred one patients were included. Median lowest SpO2 during intubation were 94% (83-98.5) with the nonrebreathing bag reservoir facemask versus 100% (95-100) with high-flow nasal cannula oxygen (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001). SpO2 values at the end of preoxygenation were higher with high-flow nasal cannula oxygen than with nonrebreathing bag reservoir facemask and were correlated with the lowest SpO2 reached during the intubation procedure (r = 0.38, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001). Patients in the nonrebreathing bag reservoir facemask group experienced more episodes of severe hypoxemia (2% vs 14%, p = 0.03). In the multivariate analysis, preoxygenation with high-flow nasal cannula oxygen was an independent protective factor of the occurrence of severe hypoxemia (odds ratio, 0.146; 95% CI, 0.01-0.90; p = 0.037). High-flow nasal cannula oxygen significantly improved preoxygenation and reduced prevalence of severe hypoxemia compared with nonrebreathing bag reservoir facemask. Its use could improve patient safety during intubation.
Statistics in Medicine, 2012
Estimating the prognostic effect of a time-dependent covariate could be tricky using a classical ... more Estimating the prognostic effect of a time-dependent covariate could be tricky using a classical Cox model, despite adjustment on other known prognostic factors. This study evaluated and compared the performance of a Cox model including the covariate occurring over time as a time-dependent covariate and the so-called &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;illness-death&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; multistate model, which is usually used to describe event-history data. We assess breast cancer prognosis related to a subsequent pregnancy occurring over time after cancer treatment in young women. We generated simulations. We considered constant and time-varying prognostic hazard ratios ( HR(t)) between patients undergoing the intermediate event and those who did not. We used both the classical Cox model and the multistate model to estimate the prognostic effect of the intermediate event HR(t). We also used the latter to estimate the covariate effect on each transition (exp(β(ij) )), thus helping to interpret HR(t) by taking into account the disease history. We applied these approaches to a female cohort treated and followed up in eight French Hospitals since 1990.
PLoS ONE, 2011
Background: Adjuvant! Online is a web-based application designed to provide 10 years survival pro... more Background: Adjuvant! Online is a web-based application designed to provide 10 years survival probability of patients with breast cancer. Several predictors have not been assessed in the original Adjuvant! Online study. We provide the validation of Adjuvant! Online algorithm on two breast cancer datasets, and we determined whether the accuracy of Adjuvant! Online is improved with other well-known prognostic factors.
PLoS ONE, 2013
Molecular signatures may become of use in clinical practice to assess the prognosis of breast can... more Molecular signatures may become of use in clinical practice to assess the prognosis of breast cancers. However, although international consensus conferences sustain the use of these new markers in the near future, concerns remain about their degree of discordance and cost-effectiveness in different international settings. The present study aims to validate Ki67 as prognostic factor in a large cohort of early-stage (pT1-pT2, pN0) breast cancer patients. 456 patients treated in 1995-1996 were identified in the Institut Curie database. Ki67 (MIB1) was retrospectively assessed by immunohistochemistry for all cases. The prognostic value of this index was compared to that of histological grade (HG), Estrogen receptor (ER) and HER2 status. Distant disease free interval, loco-regional recurrence, time-lapse from first metastatic diagnosis to death were analyzed. All 456 patients were treated by lumpectomy plus axillary dissection and radiotherapy. 27 patients (5.9%) received systemic treatment. Tumors were classified as HG1 in 35%, HG2 in 42% and HG3 in 23% of cases. ER was expressed in 86% of the tumors, HER2 in 5% and 14% were triple negative. The median follow-up was 151 [5-191] months. Distant and loco-regional disease recurrences were observed in 16% and 18%, respectively. High (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;20%) Ki67 rate [HR = 3 (1.8-4.8), p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;10e-06] and HG3 [HR = 4.4 (2.2-8.6), p = 0.00002] were associated with an increased rate of distant relapse. In multivariate analysis, the Ki67 remained the only significant prognostic factor in the subgroups of ER positive HER2 negative [HR = 2.6 (1.5-4.6), p = 0.0006] and ER positive HER2 negative HG2 tumors [HR = 2.2 (1.01-4.8), p = 0.04]. We validate the prognosis value of the Ki67 rate in small size node negative breast cancer. We conclude that Ki67 is a potential cost-effective decision marker for adjuvant therapy in early-stage HG2, pT1-pT2, pN0, breast cancers.
PLoS ONE, 2011
Background: Adjuvant! Online is a web-based application designed to provide 10 years survival pro... more Background: Adjuvant! Online is a web-based application designed to provide 10 years survival probability of patients with breast cancer. Several predictors have not been assessed in the original Adjuvant! Online study. We provide the validation of Adjuvant! Online algorithm on two breast cancer datasets, and we determined whether the accuracy of Adjuvant! Online is improved with other well-known prognostic factors.
Journal of Clinical Epidemiology, 2015
Control treatments in randomized controlled trials (RCTs) should not deliberately disadvantage pa... more Control treatments in randomized controlled trials (RCTs) should not deliberately disadvantage patients. To compare (a) willingness to include versus (b) willingness to prescribe control treatment among physicians randomized to assess, respectively, either (a) enrollment in a trial or (b) appropriateness of control treatment in a care context for the same fictional patient. Physicians were authors of articles about rheumatoid arthritis (RA), involved in RA patient care and used to enrolling patients in trials. Willingness to give control treatment: trial enrollment or control-treatment appropriateness in care context. We derived 3 case vignettes of fictional standard eligible patients for each of 30 RCTs assessing biologics in RA. Physicians were randomly allocated to the &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;trial&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; or &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;care&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; arm. For each of the 90 fictional patients, physicians assigned to the trial arm were asked if they would enroll the patient in the RCT the patient was derived from. For the same 90 fictional patients, physicians assigned to the care arm were asked if the control treatment of the RCT was appropriate in a context of usual care. Of the 1,779 physicians invited to participate, 151 were randomized. Half of the fictional patients (41/90; 45% [95%CI 37-53%]) would be enrolled in the RCT even though the control-arm treatment of the RCT was not considered appropriate for them in the context of care. This rate differed by type of comparator (55% for non-head-to-head RCTs vs 6% for head-to-head RCTs; adjusted OR (aOR) 23.9 [95%CI 5.5-92.7]) and duration of trial control treatment (56% for ≤ 24 weeks and 15% for &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 24 weeks; aOR 10.7 [95%CI 2.8-63.9]) but not patient RA activity (aOR 2.5 [95%CI 1.0-6.6]). Fictional patients, RA only. Control treatments in RCTs of biologics in RA are often deemed not acceptable in the context of usual care, especially those for non-head-to-head RCTs. These findings raise ethical concerns and challenge the choice of the comparator in RCTs.
International Journal of Antimicrobial Agents, 2015
The epidemiology of multidrug-resistant bacteria (MDRB) has changed significantly in European hea... more The epidemiology of multidrug-resistant bacteria (MDRB) has changed significantly in European healthcare settings, with a decrease in frequency of meticillin-resistant Staphylococcus aureus and an increase in extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae. Little is known about the effects of these changes on ventilator-associated pneumonia (VAP). A retrospective 5-year trend analysis of ICU antibiotic consumption and resistance in bacteria causing VAP was undertaken. Poisson regression analysis between complete microbiological data and antibiotic consumption was performed. In total, 252 episodes of VAP in 184 patients were identified between 2007 and 2011, from which 364 causal bacteria were isolated. Enterobacteriaceae isolation rates increased significantly over this period [from 6.64 to 10.52 isolates/1000 patient-days; P=0.006], mostly due to an increase in AmpC-producing Enterobacteriaceae (APE) (2.85-4.51 isolates/1000 patient-days; P=0.013), whereas the number of episodes due to S. aureus and Pseudomonas aeruginosa remained stable. A positive association was found between the increase in APE infections and an increase in past-year antibiotic consumption: amoxicillin/clavulanic acid (P=0.003), ceftazidime and cefepime (P=0.007), carbapenems (P=0.002), fluoroquinolones (P=0.012), macrolides (P=0.002) and imidazoles (P=0.004). No such association was found for the emergence of resistance in P. aeruginosa. These results indicate a change in the epidemiology of VAP, with Enterobacteriaceae exceeding P. aeruginosa and S. aureus. Moreover, a positive correlation was observed between antibiotic consumption and the incidence of potentially MDRB such as APE. No such correlation was found for ESBL-producing Escherichia coli and antibiotic-resistant P. aeruginosa.
Néphrologie & Thérapeutique, 2011
un accident ischémique transitoire (23 cas), une protéinurie > 0,5gl (24 cas), une claudication i... more un accident ischémique transitoire (23 cas), une protéinurie > 0,5gl (24 cas), une claudication intermittente : (87 cas), une HTA grade I (88 cas), grade II (47 cas), et grade III (5 cas), 3 FDR/AOC sont retrouvés chez les diabétiques (46 cas) ; une maladie cardiovasculaire (MCV) et atteinte rénale ). La moitié des patients suivis avaient une insuffisance rénale chronique (IRC) <60 mL/minute. Les mesures hygiéno-diététique (MHD) sont appliquées chez 186 patients, la bithérapie anti-HTA : (67 cas), trithérapie : (98 cas), quadrithérapie : (21 cas), statines : (126 cas), principal facteur de résistance de l'HTA : la non observance du Traitement. Discussion.-Plus de 75 % de nos patients ont un RCVG élevé (soit 140 cas), Les PA cibles selon l'OMS, atteintes chez moins de 24 % (soit 46 cas), L'obtention d'un équilibre tentionnel adéquat chez des malades tarés, présentant plus de 3 FDR est difficile et impose le recours à une poly-médication, souvent astreignante [1]. Conclusion.-L'HTA est un problème de santé majeure de santé publique [1]. La prise en charge du patient hypertendu doit reposer à la fois sur les valeurs de la pression artérielle (PA) et sur le niveau de RCVG, l'implication et la sensibilisation du malade occupe une place prépondérante dans la lutte contre les RCVG [1]. Référence [1] Agence nationale d'accréditation et d'évaluation en santé. Introduction.-Objectifs.-Chez les patients admis en réanimation pour insuffisance rénale aiguë obstructive (IRAO), déterminer les facteurs prédisant la survenue d'un syndrome de levée d'obstacle (SLO) après dérivation des urines, ou la persistance d'une insuffisance rénale chronique (IRC) sévère. Patients et méthodes.-Étude rétrospective de patients admis pour IRAO dans deux services de réanimation de 1998 à 2010. Définition du SLO : polyurie > 4L/j après dérivation des urines. Analyses uniet multivariées pour rechercher : -des facteurs prédisant la survenue du SLO ; -des facteurs prédisant la persistance d'une IRC sévère (eDFG < 30 mL/minute/1,73m2 selon le MDRD) à trois mois chez les patients indemnes d'IRC sévère avant l'épisode d'IRAO. Les résultats sont présentés en médiane (extrêmes) ou en pourcentage. Résultats.-Nous avons étudié 62 patients (âge : 70 [38-90] ans, urée plasmatique : 39 [8-166] mmo/L, créatininémie 866 [247-3119] mol/L, globe vésical 52 %). L'obstruction était due à un cancer dans 50 % des cas, un adénome de prostate dans 21 %. Un SLO est survenu dans 63 % des cas (diurèse des 24 premières heures : 7,0 [4,0-15,0] L). Les facteurs prédisant la survenue d'un SLO en analyse univariée puis multivariée étaient : l'élévation de la bicarbonatémie (odds-ratio [OR] 1,36, 95 % CI [1,13-1,65], p < 0,001), l'élévation de la créatininémie (OR 1,002, 95 % CI [1,001-1,004] p = 0,004) et la présence d'un globe vésical (OR 6,96, 95 % CI [1,34-36,23], p . Le score dérivé du modèle multivarié, calculé comme 0,31 × bicarbonatémie (mmol/L) + 0,002 × créatininémie (mol/L) + 1,95 si globe -7,15 prédisait la survenue d'un SLO avec une aire sous la courbe ROC de 0,85 (95 % CI : 0,749-0,951). Un score supérieur à 0 prédisait la survenue d'un SLO avec une sensibilité de 91 % et une spécificité (Sp) de 60 %. Parmi les 34 patients indemnes d'IRC sévère au préalable et pour lesquels un suivi à trois mois était disponible, une IRC terminale persistait dans 6 % des cas seulement, mais une IRC sévère persistait dans 21 % des cas. Les facteurs prédisant la persistance d'une IRC sévère en analyse univariée étaient : la diminution de l'hémoglobine sanguine (p < 0,001) et de la bicarbon (p = 0,03), une faible diurèse après dérivation (p = 0,03) et l'absence de SLO (p = 0,04), et une natriurèse plus élevée (p = 0,03). Une diurèse > 7,0 L/24 heures après dérivation prédisait l'absence d'IRC sévère à trois mois avec une Sp de 100 %. Une diurèse < 3,0 L prédisait la persistance d'une IRC sévère avec une Sp de 88 %. Les seuils d'hémoglobine sanguine et de bicarbonatémie les plus performants étaient respectivement de 10 g/dL et de 15 mm. Les variables d'imagerie (épaisseur du parenchyme rénal . . .) manquaient trop souvent pour être testées. Une analyse multivariée n'a pu être effectuée (taille de l'échantillon).
Journal of critical care, 2014
Renal replacement therapy (RRT) is a major supportive treatment of acute kidney injury (AKI) in i... more Renal replacement therapy (RRT) is a major supportive treatment of acute kidney injury (AKI) in intensive care unit (ICU), but the timing of its initiation remains open to debate. We retrospectively analyzed ICU patients who had AKI associated with at least one usual RRT criteria: serum creatinine concentration greater than 300 μmol/L, serum urea concentration greater than 25 mmol/L, serum potassium concentration greater than 6.5 mmol/L, severe metabolic acidosis (arterial blood pH<7.2), oliguria (urine output<135 mL/8 hours or <400 mL/24 hours), overload pulmonary edema. To estimate the risk of death associated with RRT adjusted for risk factors, we performed a marginal structural Cox model with inverse-probability-of-treatment-weighted estimator. Among 4173 patients admitted to the ICU, 203 patients fulfilled potential RRT criteria. Ninety-one patients (44.8%) received RRT and 112 (55.2%) did not. Non-RRT and RRT patients differed in terms of severity of illness: Simplifi...
BMC proceedings, 2007
In the present paper, we used the North American Rheumatoid Arthritis Consortium data provided fo... more In the present paper, we used the North American Rheumatoid Arthritis Consortium data provided for Genetic Analysis Workshop 15 Problem 2 to: 1) estimate the penetrances of PTPN22 and HLA-DRB1 and, 2) test the selected model of PTPN22 conditional on the rheumatoid factor status. To achieve these aims, we used the marker association segregation chi-square method, fitting simultaneously both genotype frequency and identical by descent distributions in a sample of 3690 White individuals from 604 nuclear families. A co-dominant model fitted the rs2476601 (R620W) single-nucleotide polymorphism (SNP) of the PTPN22 gene well, whereas a lack of fit for all models was observed for the HLA-DRB1 locus. Testing genetic models of rheumatoid arthritis that include the PTPN22 SNP in addition to the HLA-DRB1 locus did not affect the results, nor did subgroup analysis of PTPN22 conditional on the rheumatoid factor status. In conclusion, PTPN22 R620W SNP is a risk factor for rheumatoid arthritis. The...
Thrombosis Research, 2014
Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy (TMA), related to a sev... more Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy (TMA), related to a severe functional deficiency of ADAMTS13 activity (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;10% of normal). ADAMTS13 activity is thus crucial to confirm the clinical suspicion of TTP, to distinguish it from other TMAs, and to perform the follow-up of TTP patients. We compared the performance of the commercial chromogenic assay Technozym ADAMTS13 Activity ELISA (chromogenic VWF73 substrate, Chr-VWF73, Technoclone, Vienna, Austria), to that of our in-house FRETS-VWF73 used as reference method. A large group of 247 subjects (30 healthy volunteers and 217 patients with miscellaneaous TMAs) was studied. The lower limit of detection of the Chr-VWF73 was 3%, which is well adapted to the clinically relevant threshold for TTP diagnosis (10%). Our results showed a reasonable agreement between FRETS-VWF73 and Chr-VWF73 assays to distinguish samples with an ADAMTS13 activity &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;10% from those with an ADAMTS13 activity &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;10%. However, Chr-VWF73 assay provided false negative results in ~12% of acute TTP patients. Inversely, the Chr-VWF73 assay globally underestimated ADAMTS13 activity in detectable values ranging from 11 to 100% (with a great variability compared to FRETS-VWF73), which may be a concern for the follow-up of TTP patients in remission. In-house assays developed and performed by expert laboratories remain the reference methods that should be used without limitation to control values provided by commercial assays when needed. Also, the development of an international reference preparation will be crucial to improve standardization.
Obesity Surgery, 2015
Obesity induces cardiovascular alterations, including cardiac hypertrophy, impaired relaxation, a... more Obesity induces cardiovascular alterations, including cardiac hypertrophy, impaired relaxation, and heart rate variability (HRV), which are associated with increased mortality. Gastric bypass surgery (GBP) reduces cardiovascular mortality, but the mechanisms involved are not clearly established. To date, the implication of postsurgical hormonal changes has not been tested. Our aim was to study the relationships between the evolution of cardiovascular functions after GBP and changes in metabolic and hormonal parameters, including glucagon-like peptide-1 (GLP-1) and brain natriuretic peptide (N-terminal pro-brain natriuretic peptide (NT-proBNP)). Echocardiographic parameters, 24-h rhythmic Holter recording, plasma concentrations of GLP-1 before and after a test meal, and fasting NT-proBNP were assessed in 34 patients (M/F 2/32, age 36 ± 11 years, BMI 46 ± 6 kg/m(2)), before and 1 year after GBP. After GBP, excess weight loss was 79 ± 20 %. Blood pressure (BP), heart rate, and left ventricular mass decreased, while HRV and diastolic function (E/A ratio) improved. Plasma concentrations of NT-proBNP and postprandial (PP) GLP-1 increased. Changes in cardiovascular parameters were related to BMI and insulin sensitivity. Furthermore, the decrease in BP was independently associated with the increase of PP GLP-1 level and HRV was positively associated with NT-proBNP concentration after surgery. The increase in endogenous GLP-1 observed after GBP was associated with decreased BP but not with improvement of other cardiovascular parameters, whereas the increase in NT-proBNP, within the physiological range, was associated with improved HRV.
Médecine et Maladies Infectieuses, 2014
Given the increasing frequency of cefotaxime-resistant strains, third-generation cephalosporins (... more Given the increasing frequency of cefotaxime-resistant strains, third-generation cephalosporins (3GC e.g. cefotaxime, ceftriaxone) might not be recommended any longer as empirical antibiotic therapy for community-acquired Gram-negative bacteremia (CA-GNB). We conducted a multicenter prospective descriptive study including patients with CA-GNB. Two hundred and nineteen patients were included. Escherichia coli and Pseudomonas aeruginosa were the most frequently isolated species in 63% (n=138) and 11% (n=24) of the cases, respectively. The prevalence of cefotaxime-resistance reached 18% (n=39) mostly due to intrinsic resistance (27 cases, 12%). The presence of invasive material (P<0.001), the origin of the patient (Paris region or West of France) (P=0.006), and home health care (P<0.001) were variables predicting resistant GNB. The negative predictive value for resistance in patients with invasive material coming from the West of France, or without invasive material and with home health care was 94%. The positive predictive value for patients with invasive material living in Paris, or without invasive material and with home health care only reached 58 and 54%, respectively. Using 3GC for CA-GNB due to cefotaxime-resistant strains was relatively frequent, ESBL-producing Enterobacteriaceae being rarely involved. Our study highlights the role of local epidemiology; before any changes to first-line antibiotic therapy, local epidemiological data should be taken into account.
Breast, 2012
The clinical management of lobular carcinoma in situ lesions remains challenging. Our aim was to ... more The clinical management of lobular carcinoma in situ lesions remains challenging. Our aim was to evaluate the risk of relapse for lobular carcinoma in situ (LCIS) patients, diagnosed on mammography performed for microcalcifications and according to proliferation assessed by Ki67 staining. A series of 47 patient&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s files with LCIS and followed in our institution were retrospectively selected. All patients underwent lumpectomy without radiation therapy. The expression of E-cadherin, estrogen receptor (ER), progesterone receptor (PR), EGFR and Ki67 were determined. Four different classes were then defined with the following criteria: ER+ and Ki67 ≤ 10%; ER+, Ki67 &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;10%; ER-; ER-PR- and EGFR+. Patient&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s mean age was 51.3 yrs. The majority of the lesions were classical LCIS (97%). All cases were E-cadherin either negative (71%) or weak and incomplete (29%). Among the 44 evaluable cases, 34 cases were ER or PR positive with KI67 ≤ 10% (79%), 9 cases ER positive with KI67 &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 10% (21%), 1 case was ER and PR negative and expressed EGFR. At five years, all patients were alive, 1/34 ER positive and Ki67 low experienced a relapse contrasting with 3 out of 9 ER positive and Ki67 high (3 invasive carcinomas including 2 ductal and 1 lobular) (p = 0.0054). In this retrospective study, we observed a higher risk of relapse associated with a high proliferative activity of classical LCIS. If confirmed in larger series, this observation suggests that radiation therapy or hormonotherapy could be discussed for patients with Ki67 high classical LCIS in order to decrease their risk of relapse.
Breast Cancer Research, 2012
Circulating tumor cells (CTC) have been recently proposed as a new dynamic blood marker whose pos... more Circulating tumor cells (CTC) have been recently proposed as a new dynamic blood marker whose positivity at baseline is a prognostic factor and whose changes under treatment are correlated with progression-free survival (PFS) in metastatic breast cancer patients. However, serum marker levels are also used for the same purpose, and no clear comparison has been reported to date. The IC 2006-04 enrolled prospectively 267 metastatic breast cancer patients treated by first line chemotherapy and confirmed that CTC levels are an independent prognostic factor for PFS and overall survival (OS). A secondary pre-planned endpoint was to compare prospectively the positivity rates and the value of CTC (CellSearch®), of serum tumor markers (carcinoembryonic antigen (CEA), cancer antigen 15.3 (CA 15-3), CYFRA 21-1), and of serum non-tumor markers (lactate deshydrogenase (LDH), alkaline phosphatase (ALP)) at baseline and under treatment for PFS prediction, independently from the other known prognostic factors, using univariate analyses and concordance indexes. A total of 90% of the patients had at least one elevated blood marker. Blood markers were correlated with poor performance status, high number of metastatic sites and with each other. In particular, CYFRA 21-1, a marker usually used in lung cancer, was elevated in 65% of patients. A total of 86% of patients had either CA 15-3 and/or CYFRA 21-1 elevated at baseline. Each serum marker was associated, when elevated at baseline, with a significantly shorter PFS. Serum marker changes during treatment, assessed either between baseline and week 3 or between baseline and weeks 6 to 9, were significantly associated with PFS, as reported for CTC. Concordance indexes comparison showed no clear superiority of any of the serum marker or CTC for PFS prediction. For the purpose of PFS prediction by measuring blood marker changes during treatment, currently available blood-derived markers (CTC and serum markers) had globally similar performances. Besides CEA and CA 15-3, CYFRA 21-1 is commonly elevated in metastatic breast cancer and has a strong prognostic value.
SpringerPlus, 2013
The aims of the study were to investigate the factors associated with not having breast reconstru... more The aims of the study were to investigate the factors associated with not having breast reconstruction following mastectomy and to assess patient satisfaction with information on reconstruction. We analysed a historical cohort of 1937 consecutive patients who underwent mastectomy at Institut Curie between January 2004 and February 2007. Their sociodemographic and clinicobiological characteristics were recorded in a prospective database. A questionnaire was sent to 10% of nonreconstructed patients. The proportion of patients with invasive cancer was 82.7%. The rate of nonreconstruction in patients with in situ and invasive cancer was 34.6% and 74.9%, respectively. On multivariate analysis, only employment outside the home was associated with reconstruction in patients with in situ cancer (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). In patients with invasive cancer, employment status (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001) and smoking (p = 0.045) were associated with reconstruction, while age &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 50, ASA score &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;1, radiotherapy (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001) and metastatic status (p = 0.018) were associated with nonreconstruction. For 80% of questionnaire responders, nonreconstruction was a personal choice, mainly for the following reasons: refusal of further surgery, acceptance of body asymmetry, risk of complications and advanced age. Information on reconstruction was entirely unsatisfactory or inadequate for 62% of patients. Better understanding the factors that influence decision of nonreconstruction can help us adapt the information to serve the patient&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s personal needs.
Progrès en urologie : journal de l'Association française d'urologie et de la Société française d'urologie, 2009
Nephron sparing surgery raises the challenge of avoiding chronic haemodialysis for patients havin... more Nephron sparing surgery raises the challenge of avoiding chronic haemodialysis for patients having malignancies on a solitary kidney. The aim of this study was to estimate the long term renal function, survival and risk of recurrence of patients undergoing elective nephron sparing surgery for renal cancer on a solitary kidney. Between January 1975 and December 2002, 37 elective nephron sparing surgery of kidney tumors were performed on 33 patients with a solitary kidney. Surgery was performed without interruption of blood flow. Pre- and postoperative renal function were compared by using a non parametric test of Kruskal and Wallis. Survival rates were estimated by the Kaplan Meier method and the prognostic factors were defined on a multivariate analysis using a Cox model. Mean tumoral diameter was 4.6 cm [1.5-10]. The median follow-up was of 83 months. Three patients died in the postoperative period. The postoperative creatinine clairance was significantly lower than the preoperativ...
Critical Care Medicine, 2014
Tracheal intubation of ICU patients is frequently associated with severe hypoxemia. Although noni... more Tracheal intubation of ICU patients is frequently associated with severe hypoxemia. Although noninvasive ventilation reduces desaturation during intubation of severely hypoxemic patients, it does not allow for per-procedure oxygenation and has not been evaluated in mild-to-moderate hypoxemic patients for whom high-flow nasal cannula oxygen may be an alternative. We sought to compare pre- and per-procedure oxygenation with either a nonrebreathing bag reservoir facemask or a high-flow nasal cannula oxygen during tracheal intubation of ICU patients. Prospective quasi-experimental before-after study (ClinicalTrials.gov: NCT01699880). University hospital medico-surgical ICU. All adult patients requiring tracheal intubation in the ICU were eligible. In the control (before) period, preoxygenation was performed with a nonrebreathing bag reservoir facemask and in the change of practice (after) period, with high-flow nasal cannula oxygen. Primary outcome was median lowest SpO2 during intubation, and secondary outcomes were SpO2 after preoxygenation and number of patients with saturation less than 80%. One hundred one patients were included. Median lowest SpO2 during intubation were 94% (83-98.5) with the nonrebreathing bag reservoir facemask versus 100% (95-100) with high-flow nasal cannula oxygen (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001). SpO2 values at the end of preoxygenation were higher with high-flow nasal cannula oxygen than with nonrebreathing bag reservoir facemask and were correlated with the lowest SpO2 reached during the intubation procedure (r = 0.38, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001). Patients in the nonrebreathing bag reservoir facemask group experienced more episodes of severe hypoxemia (2% vs 14%, p = 0.03). In the multivariate analysis, preoxygenation with high-flow nasal cannula oxygen was an independent protective factor of the occurrence of severe hypoxemia (odds ratio, 0.146; 95% CI, 0.01-0.90; p = 0.037). High-flow nasal cannula oxygen significantly improved preoxygenation and reduced prevalence of severe hypoxemia compared with nonrebreathing bag reservoir facemask. Its use could improve patient safety during intubation.
Statistics in Medicine, 2012
Estimating the prognostic effect of a time-dependent covariate could be tricky using a classical ... more Estimating the prognostic effect of a time-dependent covariate could be tricky using a classical Cox model, despite adjustment on other known prognostic factors. This study evaluated and compared the performance of a Cox model including the covariate occurring over time as a time-dependent covariate and the so-called &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;illness-death&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; multistate model, which is usually used to describe event-history data. We assess breast cancer prognosis related to a subsequent pregnancy occurring over time after cancer treatment in young women. We generated simulations. We considered constant and time-varying prognostic hazard ratios ( HR(t)) between patients undergoing the intermediate event and those who did not. We used both the classical Cox model and the multistate model to estimate the prognostic effect of the intermediate event HR(t). We also used the latter to estimate the covariate effect on each transition (exp(β(ij) )), thus helping to interpret HR(t) by taking into account the disease history. We applied these approaches to a female cohort treated and followed up in eight French Hospitals since 1990.
PLoS ONE, 2011
Background: Adjuvant! Online is a web-based application designed to provide 10 years survival pro... more Background: Adjuvant! Online is a web-based application designed to provide 10 years survival probability of patients with breast cancer. Several predictors have not been assessed in the original Adjuvant! Online study. We provide the validation of Adjuvant! Online algorithm on two breast cancer datasets, and we determined whether the accuracy of Adjuvant! Online is improved with other well-known prognostic factors.
PLoS ONE, 2013
Molecular signatures may become of use in clinical practice to assess the prognosis of breast can... more Molecular signatures may become of use in clinical practice to assess the prognosis of breast cancers. However, although international consensus conferences sustain the use of these new markers in the near future, concerns remain about their degree of discordance and cost-effectiveness in different international settings. The present study aims to validate Ki67 as prognostic factor in a large cohort of early-stage (pT1-pT2, pN0) breast cancer patients. 456 patients treated in 1995-1996 were identified in the Institut Curie database. Ki67 (MIB1) was retrospectively assessed by immunohistochemistry for all cases. The prognostic value of this index was compared to that of histological grade (HG), Estrogen receptor (ER) and HER2 status. Distant disease free interval, loco-regional recurrence, time-lapse from first metastatic diagnosis to death were analyzed. All 456 patients were treated by lumpectomy plus axillary dissection and radiotherapy. 27 patients (5.9%) received systemic treatment. Tumors were classified as HG1 in 35%, HG2 in 42% and HG3 in 23% of cases. ER was expressed in 86% of the tumors, HER2 in 5% and 14% were triple negative. The median follow-up was 151 [5-191] months. Distant and loco-regional disease recurrences were observed in 16% and 18%, respectively. High (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;20%) Ki67 rate [HR = 3 (1.8-4.8), p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;10e-06] and HG3 [HR = 4.4 (2.2-8.6), p = 0.00002] were associated with an increased rate of distant relapse. In multivariate analysis, the Ki67 remained the only significant prognostic factor in the subgroups of ER positive HER2 negative [HR = 2.6 (1.5-4.6), p = 0.0006] and ER positive HER2 negative HG2 tumors [HR = 2.2 (1.01-4.8), p = 0.04]. We validate the prognosis value of the Ki67 rate in small size node negative breast cancer. We conclude that Ki67 is a potential cost-effective decision marker for adjuvant therapy in early-stage HG2, pT1-pT2, pN0, breast cancers.