Notre-Dame-de-l'Île-Perrot, Canada
Notre-Dame-de-l'Île-Perrot, Canada

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Wildi L.M.,University of Montréal | Raynauld J.-P.,University of Montréal | Martel-Pelletier J.,University of Montréal | Beaulieu A.,Laval University | And 4 more authors.
Annals of the Rheumatic Diseases | Year: 2011

Objective To determine the effect of chondroitin sulphate (CS) treatment on cartilage volume loss, subchondral bone marrow lesions (BML), synovitis and disease symptoms in patients with knee osteoarthritis (OA). Methods In this pilot multicentre, randomised, doubleblind, controlled trial in primary knee OA, 69 patients with clinical signs of synovitis were randomised to receive CS 800 mg or placebo once daily for 6 months followed by an open-label phase of 6 months in which patients in both groups received CS 800 mg once daily. Cartilage volume and BML were assessed by MRI at baseline and at 6 and 12 months; synovial membrane thickness was assessed at baseline and at 6 months. Results The CS group showed significantly less cartilage volume loss than the placebo group as early as 6 months for the global knee (p=0.030), lateral compartment (p=0.015) and tibial plateaus (p=0.002), with significance persisting at 12 months. Significantly lower BML scores were found for the CS group at 12 months in the lateral compartment (p=0.035) and the lateral femoral condyle (p=0.044). Disease symptoms were similar between the two groups. Conclusion CS treatment significantly reduced the cartilage volume loss in knee OA starting at 6 months of treatment, and BML at 12 months. These findings suggest a joint structure protective effect of CS and provide new in vivo information on its mode of action in knee OA.

Roubille C.,University of Montréal | Raynauld J.-P.,University of Montréal | Abram F.,EST Inc | Paiement P.,EST Inc | And 5 more authors.
Arthritis Research and Therapy | Year: 2014

Introduction: Pain in osteoarthritis (OA) has been classically attributed to joint structural damage. Disparity between the degree of radiographic structural damage and the severity of symptoms implies that factors other than the joint pathology itself contribute to the pain. Peripheral and central sensitization have been suggested as two of the underlying mechanisms that contribute to pain in OA. The aim of this study was to explore in symptomatic knee OA patients, the structural changes assessed by magnetic resonance imaging (MRI) that could be used as markers of neuropathic pain (NP). Methods: This cross-sectional observational pilot study included 50 knee OA patients with moderate to severe pain (VAS ≥40) in the target knee. The presence of NP was determined based on the PainDETECT questionnaire. Among the 50 patients included, 25 had PainDETECT score ≤12 (unlikely NP), 9 had PainDETECT score between 13 and 18 (uncertain NP) and 16 had PainDETECT score ≥19 (likely NP). WOMAC, PainDETECT, and VAS pain scores as well as knee MRI were assessed. Results: Data showed no significant difference in demographic characteristics between the three groups. However, a positive and statistically significant association was found between the WOMAC pain (P <0.001), function (P <0.001), stiffness (P=0.007) and total (P <0.001) scores as well as higher VAS pain score (P=0.023), and PainDETECT scores. Although no difference was found in the cartilage volume between groups, the presence of meniscal extrusion in both medial (P=0.006) and lateral (P=0.023) compartments, and presence of meniscal tears in the lateral compartment (P=0.011), were significantly associated with increasing PainDETECT score. Moreover, the presence of bone marrow lesions in the lateral plateau and the extent of the synovial membrane thickness in the lateral recess were associated with increasing PainDETECT scores (P=0.032, P=0.027, respectively). Conclusions: In this study, meniscal lesions, particularly extrusion, were found to be among the strongest risk factors for NP in knee OA patients. © 2014 Roubille et al.

Henri C.,University of Montréal | Giraldeau G.,University of Montréal | Dorais M.,StatSciences Inc | Cloutier A.-S.,University of Montréal | And 7 more authors.
Circulation: Arrhythmia and Electrophysiology | Year: 2012

Background-Atrial fibrillation (AF) is common after thoracic surgery. Limited data exist concerning the incidence of AF, its impact on mortality, the effectiveness of therapy, and the risk factors of AF after pulmonary transplantation. Methods and Results-We reviewed the medical files of 224 consecutive lung transplant recipients who underwent surgery over a 10-year period at a large Canadian center. We collected patient characteristics, in-hospital treatments, and outcomes. Time-to-event analysis was used to account for in-hospital follow-up and models generated to assess the impact of AF on mortality and independent risk factors of AF after transplantation. Postoperative AF occurred in 65 patients (29%). AF was more likely to occur with complications such as pneumonia, mediastinitis, and bronchial dehiscence and was not an independent risk factor of mortality (hazard ratio=1.56; 95% confidence interval, 0.52- 4.63). Pharmacological or electric therapy for rhythm or rate control of AF was administered to 97% of patients. Intravenous amiodarone was used in 46%, electric cardioversion in 28%, and heparin in 26%. Only 1 patient remained in AF at discharge. Age (hazard ratio=1.08 by year; 95% confidence interval, 1.05-1.12), bilateral transplantation (hazard ratio=1.87; 95% confidence interval, 1.03-3.42), and a history of AF before the transplantation (hazard ratio=4.48; 95% confidence interval, 1.05-19.11) were found to be independently associated with an increased incidence of postoperative AF. Conclusions-AF is fairly common after pulmonary transplantation, transient, and relatively benign. It is not independently associated with increased in-hospital mortality. Most patients return to sinus rhythm before discharge. Age, prior AF, and bilateral transplantation increase the risk of postoperative AF. © 2012 American Heart Association, Inc.

Martel-Pelletier J.,University of Montréal | Roubille C.,University of Montréal | Abram F.,ArthroLab Inc. | Hochberg M.C.,University of Maryland, Baltimore | And 4 more authors.
Annals of the Rheumatic Diseases | Year: 2013

Objective: To determine, using data from participants enrolled in the progression cohort of the OAI, the effects of conventional osteoarthritis (OA) pharmacological treatment and those of the combination of glucosamine and chondroitin sulfate (Glu/CS) on knee structural changes. Methods: Six hundred patients with knee OA were stratified based on whether or not they received for 24 consecutive months the OA conventional pharmacological treatment and/or Glu/CS. The main outcomes were knee structural changes, including the loss of joint space width (JSW) and of cartilage volume measured by quantitative MRI. Results: Participants reported taking (+) (n=300) or not taking (-) (n=300) OA treatment (analgesic/NSAIDs). The +analgesic/NSAIDs participants had higher Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores (p<0.001) and smaller JSW (p=0.01), reflecting more severe disease at baseline. In the -analgesic/NSAIDs group, participants taking Glu/CS had significantly reduced loss of cartilage volume at 24 months in the medial central plateau (p=0.007). Further subdivision revealed that this effect of Glu/CS occurred in participants with a higher severity of the disease (JSW≤median). In the +analgesic/NSAIDs group, those taking Glu/CS had significantly reduced loss of cartilage volume in the global plateau at 12 months (p=0.05), and in the central plateau at 24 months (p=0.05). These effects occurred in participants with less disease severity (JSW>median). By contrast, no significant reduction in JSW was found between all groups. Conclusions: In +analgesic/NSAIDs groups and -analgesic/NSAIDs groups, participants who took Glu/CS had reduced loss of cartilage volume over 24 months in subregions when assessed with qMRI, arguing for a disease-modifying effect of Glu/CS which could not be identified by X-rays. © 2013 BMJ Publishing Group Ltd & European League Against Rheumatism.

Pelletier J.-P.,University of Montréal | Roubille C.,University of Montréal | Raynauld J.-P.,University of Montréal | Abram F.,ArthroLab Inc. | And 3 more authors.
Annals of the Rheumatic Diseases | Year: 2013

Objective: To explore, using MRI, the disease-modifying effect of strontium ranelate (SrRan) treatment on cartilage volume loss (CVL) and bone marrow lesions (BMLs) in a subset of patients from a Phase III clinical trial in knee osteoarthritis (OA) (SrRan Efficacy in Knee OsteoarthrItis triAl (SEKOIA)). Material and methods: Patients with primary symptomatic knee OA were randomised to receive either SrRan 1 g/day or 2 g/day or placebo (SEKOIA study). A subset of these patients had MRIs at baseline, 12, 24 and 36 months to assess the knee cartilage volume and BMLs. Missing values were imputed and the analyses were adjusted according to Bonferroni. Results: In this MRI subset, the distribution of patients (modified intention-to-treat; n=330) was 113, 105 and 112 for SrRan 1 g/day, 2 g/day and placebo, respectively. The groups were fairly balanced at baseline regarding demographics, clinical symptoms or imaging characteristics. Treatment with SrRan 2 g/day significantly decreased CVL on the plateaus at 12 (p=0.002) and 36 (p=0.003) months compared with placebo. Of note, in the medial femur and plateau, SrRan 1 g/day, but not SrRan 2 g/day, had more CVL than placebo. In patients with BML in the medial compartment at baseline, the BML score at 36 months was decreased in both treatment groups compared with the placebo group (SrRan 1 g/day, p=0.002 and SrRan 2 g/day p=0.001, respectively), and CVL significantly decreased with SrRan 2 g/day (p=0.023) in the plateau compared with placebo. Conclusions: In knee OA patients, treatment with SrRan 2 g/day was found to have beneficial effects on structural changes by significantly reducing CVL in the plateau and BML progression in the medial compartment. © 2013 BMJ Publishing Group Ltd & European League Against Rheumatism.

Roubille C.,University of Montréal | Martel-Pelletier J.,University of Montréal | Raynauld J.-P.,University of Montréal | Abram F.,ArthroLab Inc | And 3 more authors.
Arthritis Research and Therapy | Year: 2015

Introduction: To evaluate the impact of meniscal extrusion (Ext) on knee osteoarthritis (OA) structural progression and on response to strontium ranelate (SrRan) treatment at 36months in patients with (+) or without (-) Ext, in association (+) or not (-) with bone marrow lesions (BML) in the medial compartment using X-rays (JSW) and qMRI. Methods: Patients from the qMRI substudy of the SEKOIA trial (SrRan 1g/day, n=113; SrRan 2g/day, n=105; placebo, n=112) were stratified based on whether meniscal extrusion and/or BML were present or not in the medial compartment. Results: In the placebo group, Ext+patients (n=26) had more JSW loss (p=0.002) and cartilage volume loss in the global knee (p=0.034) and plateau (p=0.005), and medial compartment (p=0.0005) than Ext- patients (n=86). Ext-BML+ patients (n=18) demonstrated more JSW loss (p=0.003) and cartilage volume loss in the global (p=0.020) and medial femur (p=0.055) than Ext-BML- (n=68). Compared to Ext+BML- (n=14), Ext+BML+ patients (n=12) had more cartilage volume loss in the global femur (p=0.028), with no change in JSW. The JSW loss (p=0.0004) and cartilage volume loss (global knee, p=0.033, medial compartment, p=0.0005) were greater when Ext and BML were simultaneously present in the medial compartment. SrRan 2g/day treatment demonstrated a reduction in OA knee structural progression with qMRI, but not with JSW, in which less cartilage volume loss was found in the plateaus (p=0.007) in Ext+patients (n=15), and in the medial plateau (p=0.046) in patients in whom both Ext and BML were co-localized. Conclusion: The findings of this study are novel and could have an impact on future strategies regarding clinical trials. Indeed, data first argue for a combined, cumulative effect of meniscal extrusion and bone marrow lesions on cartilage loss and, secondly, they showed that SrRan may have protective effects in OA patients with meniscal extrusion as well as when both meniscal extrusion and BML are co-localized. © Roubille et al.; licensee BioMed Central.

Kouz J.,McGill University | Vincent C.,University of Montréal | Leong A.,McGill University | Dorais M.,StatSciences Inc. | Rakel A.,University of Montréal
Liver Transplantation | Year: 2014

Post transplant weight gain is common after orthotopic liver transplantation. We sought to determine the extent of weight gain at 5 years after transplantation in patients with nonalcoholic fatty liver disease (NAFLD) cirrhosis versus patients with other types of cirrhosis (non-NAFLD). We studied 126 liver transplants performed between 2005 and 2007 at Saint Luc Hospital, University of Montreal. Seventeen of the 126 patients (13.5%) had NAFLD cirrhosis. Ascites volume was difficult to assess, so we used the body mass index (BMI) at 3 months as the reference BMI. All patients gained weight after transplantation, but BMI increased significantly more and earlier among the NAFLD patients [4.8 versus 1.5 kg/m2 at 1 year (P=0.001), 5.0 versus 2.3 kg/m2 at 2 years (P=0.01), and 5.6 versus 2.6 kg/m2 at 5 years (P=0.009)] in comparison with non-NAFLD patients in unadjusted analyses. The greatest BMI increase over time was investigated with univariate and multivariate logistic regression analyses. The BMI increase was divided into tertiles for each period of time observed. The greatest BMI increase over time was defined as the top tertile of BMI increase. After adjustments for potential confounders (ie, total cholesterol, diabetes, and length of hospital stay), NAFLD was no longer associated with a risk of a greater BMI increase [odds ratio (OR)=3.73 at 1 year (P-0.11), OR=2.15 at 2 years (P=0.34), and OR=2.87 at 5 years (P=0.30)]. These findings suggest the need for multidisciplinary, early, and close weight monitoring for all patients. All patients could benefit from pretransplant counseling regarding weight gain and its consequences. Liver Transpl 20:1266-1274, 2014. © 2014 AASLD.

Raynauld J.-P.,University of Montréal | Martel-Pelletier J.,University of Montréal | Haraoui B.,University of Montréal | Choquette D.,University of Montréal | And 4 more authors.
Annals of the Rheumatic Diseases | Year: 2011

Objective: To identify predictive factors for total knee replacement (TKR) using data from MRI of knee osteoarthritis patients in a phase III multicentre disease-modifying osteoarthritis drug (DMOAD) study. Methods: Knee osteoarthritis patients from a 2-year clinical trial evaluating licofelone versus naproxen were investigated for the incidence of TKR of the study knee. Patients (n=161) who completed the study according to protocol were selected. Incidence of TKR was assessed blindly to the treatment following telephone interviews (n=123). Results: 18 TKR (14.6%) were performed in 4-7 years following enrolment in the original study. More TKR were performed within the naproxen than the licofelone group (61% vs 39%, p=0.232). Baseline score of bone marrow lesions (BML) in the medial compartment (p=0.0001), medial joint space width (JSW) as assessed by standardised radiographs (p=0.0008), presence of severe medial meniscal tear (p=0.004), medial meniscal extrusion (p=0.013), and C-reactive protein level (p=0.049) were strong predictors of TKR. Changes at the end of the study also yielded strong predictors: change in cartilage volume of the medial compartment (p=0.005) and of the global knee (p=0.034), reduction in the JSW of greater than 7% (p=0.009), and WOMAC pain (p=0.009) and function (p=0.023) scores. Multivariate analysis showed that baseline severe medial meniscal tear (p=0.023) and presence of medial BML (p=0.025) were the strongest independent long-term predictors of TKR. Conclusion: This study shows that in the context of osteoarthritis trials, clinical data and structural changes identified by MRI allow prediction of a 'hard' outcome such as TKR. The findings support the usefulness and predictive value of MRI in defining study outcome in DMOAD trials.

Li W.,ArthroVision Inc. | Abram F.,ArthroVision Inc. | Pelletier J.-P.,University of Montréal | Raynauld J.-P.,University of Montréal | And 3 more authors.
Arthritis Research and Therapy | Year: 2010

Introduction: Joint effusion is frequently associated with osteoarthritis (OA) flare-up and is an important marker of therapeutic response. This study aimed at developing and validating a fully automated system based on magnetic resonance imaging (MRI) for the quantification of joint effusion volume in knee OA patients.Methods: MRI examinations consisted of two axial sequences: a T2-weighted true fast imaging with steady-state precession and a T1-weighted gradient echo. An automated joint effusion volume quantification system using MRI was developed and validated (a) with calibrated phantoms (cylinder and sphere) and effusion from knee OA patients; (b) with assessment by manual quantification; and (c) by direct aspiration. Twenty-five knee OA patients with joint effusion were included in the study.Results: The automated joint effusion volume quantification was developed as a four stage sequencing process: bone segmentation, filtering of unrelated structures, segmentation of joint effusion, and subvoxel volume calculation. Validation experiments revealed excellent coefficients of variation with the calibrated cylinder (1.4%) and sphere (0.8%) phantoms. Comparison of the OA knee joint effusion volume assessed by the developed automated system and by manual quantification was also excellent (r = 0.98; P < 0.0001), as was the comparison with direct aspiration (r = 0.88; P = 0.0008).Conclusions: The newly developed fully automated MRI-based system provided precise quantification of OA knee joint effusion volume with excellent correlation with data from phantoms, a manual system, and joint aspiration. Such an automated system will be instrumental in improving the reproducibility/reliability of the evaluation of this marker in clinical application. © 2010 Martel-Pelletier et al.; licensee BioMed Central Ltd.

Pelletier J.-P.,University of Montréal | Raynauld J.-P.,University of Montréal | Caron J.,University of Montréal | Mineau F.,University of Montréal | And 5 more authors.
Annals of the Rheumatic Diseases | Year: 2010

Objectives: To explore the impact of disease-modifying osteoarthritis drug (DMOAD) treatment on biomarker levels and their correlation with cartilage volume loss and disease symptoms in a 2-year phase III clinical trial in patients with knee OA. Methods: 161 patients with knee OA (according-to-protocol population) were selected from a 2-year DMOAD trial studying the effect of licofelone (200 mg twice daily) versus naproxen (500 mg twice daily). Clinical evaluation of patients was carried out using the Western Ontario and McMaster Universities (WOMAC) questionnaire. Biomarker measurements of matrix metalloproteinase (MMP)-1, MMP-3, interleukin (IL)-6, C reactive protein (CRP), cartilage oligomeric matrix protein (COMP) and type I collagen C-terminal telopeptide (CTX-I) in serum, type II collagen C-terminal telopeptide (CTX-II) in urine, and knee MRI were performed at baseline and 2 years. Results: Over time an increase occurred in all biomarker levels with the exception of IL-6, CRP and CTX-II which decreased. The increase in MMP-1 and MMP-3 was significantly less (p=0.05; p<0.01, respectively) in the licofelone group. The baseline MMP-1 level was significantly but inversely predictive of cartilage volume loss for the medial compartment in both univariate (p=0.04) and multivariate (p≤0.04) regression analyses, and COMP, a predictor for the lateral compartment, in both univariate and multivariate models (p<0.01). Baseline levels of IL-6 and CRP also showed a significant relationship with volume loss for the medial compartment (univariate analysis, p=0.04 and p=0.01, respectively; multivariate analysis, p=0.03, p=0.01). A significant association (univariate) was observed between the change in the levels of MMP-1 (p=0.03) and MMP-3 (p=0.02) and cartilage volume loss (lateral compartment) over 2 years. Baseline levels of CTX-I correlated (p=0.02) with an increase in the size of the bone marrow lesion in the medial compartment. The baseline CRP levels correlated with worsening of symptoms: WOMAC total index (p<0.01), pain (p<0.01) and function (p<0.01). Conclusion: Higher baseline values of IL-6, CRP and COMP are predictive of greater risk of cartilage loss in OA. However, over time a reduction in MMP-1 and MMP-3 levels correlated best with reduction in cartilage volume loss and the effect of drug treatment. Baseline CRP was found to be a good predictor of the symptomatic response to treatment.

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