Philippe Broët's research while affiliated with CHU Sainte-Justine and other places
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Publications (128)
Background
Despite the growing utility of cardiovascular magnetic resonance (CMR) for cardiac morphology and function, sex and age-specific normal reference values derived from large, multi-ethnic data sets are lacking. Furthermore, most available studies use a simplified tracing methodology. Using a large cohort of participants without history of...
Objectives
We will enrich the cancer research ecosystem in Canada through linking cancer registry and administrative health data to the Canadian Partnership for Tomorrow’s Health (CanPath) cohort and biobank. CanPath is Canada’s largest population health study, including 1% of the Canadian population, which seeks to investigate cancer development....
Objectives
Around 30% of patients with rheumatoid arthritis (RA) do not respond to tumour necrosis factor inhibitors (TNFi). We aimed to predict patient response to TNFi using machine learning on simple clinical and biological data.
Methods
We used data from the RA ESPOIR cohort to train our models. The endpoints were the EULAR response and the ch...
Despite being assayed on commercialized DNA chips, the X chromosome is commonly excluded from genome-wide association studies (GWAS). One of the reasons is the complexity to analyze the data taking into account the X-chromosome inactivation (XCI) process in women and in particular the XCI process with a potentially skewed pattern. This is the case...
Background
Thirteen drugs with different mechanisms of action may be considered to treat patients with methotrexate (MTX) inadequate response in rheumatoid arthritis (RA). TNF inhibitors (TNFi) are frequently the first choice in this situation. Unfortunately, 30% to 40% of RA patients do not respond to TNFi, resulting in a delay for beginning the a...
To compare two or more survival distributions with interval‐censored data, various nonparametric tests have been proposed. Some are based on the Gρ$$ {G}^{\rho } $$‐family introduced by Harrington and Fleming (1991) that allows flexibility for situations in which the hazard ratio decreases monotonically to unity. However, it is unclear how to choos...
Introduction:
The objective of this study was to characterize the combinations of demographic and socioeconomic characteristics associated to the unwillingness to receive the COVID-19 vaccines during the 2021 Quebec's vaccination campaign.
Materials and methods:
In March-June 2021, we conducted an online survey of the participants of the CARTaGE...
The objective was to evaluate the predictive performance of the Colorectal Cancer Risk Assessment Tool (CCRAT) and three polygenic risk scores (Hsu et al., 2015, Law et al., 2019, Archambault et al. 2020) to predict the occurrence of colorectal cancer at five years in a Quebec population-based cohort. By using the CARTaGENE cohort, we computed the...
Background
In the Canadian Alliance for Healthy Hearts and Minds (CAHHM) cohort, participants underwent magnetic resonance imaging (MRI) of the brain, heart, and abdomen, that generated incidental findings (IFs). The approach to managing these unexpected results remain a complex issue. Our objectives were to describe the CAHHM policy for the manage...
Introduction
The Canadian Partnership for Tomorrow’s Health (CanPath) is a multi-centered prospective cohort study, and represents Canada’s largest population health research platform. CanPath holds data and biosamples on more than 330,000 participants from five regional cohorts representing British Columbia, Alberta, Ontario, Quebec, Nova Scotia,...
MicroAbstract: Integration of Next Generation Sequencing (NGS) information for use in distinguishing between Multiple Primary Lung Cancer and intrapulmonary metastasis was evaluated. We used a probabilistic model, comprehensive histologic assessment and NGS to classify patients. Integrating NGS data confirmed initial diagnosis (n = 41), revised the...
Introduction
Occupational exposures are related to occupational diseases burden and increased susceptibility to health issues. The joint assessment of occupational exposure and disease outcome is the key to accelerate breakthroughs in occupational health research.
Objectives
Occupational data including coding of occupations and exposure assessment...
Objective
To determine whether cognitive reserve attenuates the association of vascular brain injury with cognition.
Methods
Cross-sectional data were analyzed from two harmonized studies: the Canadian Alliance for Healthy Hearts and Healthy Minds (CAHHM) and the Prospective Urban and Rural Epidemiology (PURE) study. Markers of cognitive reserve w...
Background
By mid-July 2020, more than 108,000 COVID-19 cases had been diagnosed in Canada with more than half in the province of Quebec. In this context, we launched a study to analyze the epidemiological characteristics and the socio-economic impact of the spring outbreak in the population.
Method
We conducted an online survey of the participant...
Objectives
Evaluate the accuracy of the Breast Cancer Risk Assessment Tool (BCRAT), International Breast Cancer Intervention Study risk evaluation tool (IBIS), Polygenic Risk Scores (PRS) and combined scores (BCRAT+PRS and IBIS +PRS) to predict the occurrence of invasive breast cancers at 5 years in a French-Canadian population.
Design
Population-...
Background
Diabetes is a risk factor for cerebrovascular disease and cognitive impairment. The anatomical basis for this is uncertain.
Methods
The Canadian Alliance for Healthy Hearts and Minds (CAHHM) collected brain and carotid magnetic resonance imaging (MRI) and two cognitive tests (DSST and MoCA) in a cross-sectional sample of men and women....
BACKGROUND: Biopharmaceutical products (BPs) are widely used to treat autoimmune diseases, but immunogenicity limits their efficacy for an important proportion of patients. Our knowledge of patient-related factors influencing the occurrence of antidrug antibodies (ADAs) is still limited. METHODS AND FINDINGS: The European consortium ABIRISK (Anti-B...
Background: By mid-July 2020, more than 108,000 COVID-19 cases had been diagnosed in Canada with more than half in the province of Quebec. To be prepared for a potential second wave of COVID-19 in the fall, it seems of utmost importance to analyze the epidemiological and socio-economic characteristics of the spring outbreak in the population.
Metho...
Background: By mid-July 2020, more than 108,000 COVID-19 cases had been diagnosed in Canada with more than half in the province of Quebec. To be prepared for a potential second wave of COVID-19 in the fall, it seems of utmost importance to analyze the epidemiological and socioeconomic characteristics of the spring outbreak in the population.
Metho...
Background
The intent of the Canadian Alliance for Healthy Hearts and Minds (CAHHM) cohort is to understand the early determinants of subclinical cardiac and vascular disease and progression in adults selected from existing cohorts; the Canadian Partnership for Tomorrow Project (CPTP), the Prospective Urban and Rural Evaluation (PURE) cohort and, t...
Neural networks have been investigated as models for survival data using a training criterion similar to that of the Cox proportional hazards model, a criterion not designed for clinical prediction. In this paper, we develop a new survival learning algorithm where a neural network ensemble minimizes the integrated Brier score. We compare the result...
With the increasing use of polygenic risk scores (PRS) there is a need for adapted methods to evaluate the predictivity of these tools. In this work, we propose a new pseudo-R2 criterion to evaluate PRS predictive accuracy for time-to-event data. This new criterion is related to the score statistic derived under a two-component mixture model. It ev...
Predicting immunogenicity for biotherapies using patient and drug-related factors represents nowadays a challenging issue. With the growing ability to collect massive amount of data, machine learning algorithms can provide efficient predictive tools. From the bio-clinical data collected in the multi-cohort of autoimmune diseases treated with biothe...
Background:
With the growth in use of biotherapic drugs in various medical fields, the occurrence of anti-drug antibodies represents nowadays a serious issue. This immune response against a drug can be due either to pre-existing antibodies or to the novel production of antibodies from B-cell clones by a fraction of the exposed subjects. Identifyin...
Therapeutic proteins and emerging gene and cell-based therapies are attractive therapeutic tools for addressing unmet medical needs or when earlier conventional treatment approaches failed. However, the development of an immune response directed against therapeutic agents is a significant concern as it occurs in a substantial number of cases across...
Household air pollution (HAP) is of public health concern, with ~3 billion people worldwide (including >15 million in the US) exposed. HAP from coal use is a human lung carcinogen, yet the epidemiological evidence on carcinogenicity of HAP from biomass use, primarily wood, is not conclusive. To robustly assess biomass’s carcinogenic potential, pros...
Replacement therapy in severe hemophilia A leads to factor VIII (FVIII) inhibitors in 30% of patients. Factor VIII gene (F8) mutation type, a family history of inhibitors, ethnicity and intensity of treatment are established risk factors, and were included in two published prediction tools based on regression models. Recently investigated immune re...
Two validated assays, a bridging ELISA and a luciferase-based bioassay, were compared for detection of anti-drug antibodies (ADA) against interferon-beta (IFN-β) in patients with multiple sclerosis. Serum samples were tested from patients enrolled in a prospective study of 18 months. In contrast to the ELISA, when IFN-β-specific rabbit polyclonal a...
Abstract
Objectives
To evaluate the incidence of anti-drug antibody (ADA) occurrences and ADA-related risk factors under adalimumab and infliximab treatment in rheumatoid arthritis (RA) patients.
Methods
The study combined retrospective cohorts from the ABIRISK project totaling 366 RA patients treated with adalimumab (n= 240) or infliximab (n=126),...
Multiple sclerosis (MS) is an autoimmune disease characterized by CNS inflammation leading to demyelination and axonal damage. IFN-β is an established treatment for MS; however, up to 30% of IFN-β–treated MS patients develop neutralizing antidrug antibodies (nADA), leading to reduced drug bioactivity and efficacy. Mechanisms driving antidrug immuno...
Multiple sclerosis (MS) is an autoimmune disease characterized by CNS inflammation leading to demyelination and axonal damage. IFN-β is an established treatment for MS; however, up to 30% of IFN-β-treated MS patients develop neutralizing antidrug antibodies (nADA), leading to reduced drug bioactivity and efficacy. Mechanisms driving antidrug immuno...
In phase II oncology trials, the use of new cytostatic drugs raises some questions regarding the endpoint. Time-to-event endpoints such as Progression-Free Survival have been recommended and led to new designs. In 2003, Case and Morgan proposed a design based on the comparison of the cumulative hazards at a clinically relevant timepoint. In 2013, K...
Several tests have been recently implemented in the nonparametric comparison of current status survival data. However, they are not suited for the situation of crossing hazards. In this setting, we propose a new test specifically designed for crossing hazards alternatives. The proposed test is compared to classical implemented tests through simulat...
Objectives:
In cross-sectional studies of time-to-event data collected by patient examinations at a single random point in time, a fraction of them will not experience the event regardless of the length of the follow-up time. This is the case in clinical immunology studies that include a mixed population, with both immune-reactive and immune-toler...
Cholangiocarcinoma (CCA) is a hepatobiliary malignancy exhibiting high incidence in countries with endemic liver-fluke infection. We analyzed 489 CCAs from 10 countries, combining whole-genome (71 cases), targeted/exome, copy-number, gene expression, and DNA methylation information. Integrative clustering defined 4 CCA clusters—fluke-positive CCAs...
Proportion of samples per IFNβ preparation tested by each assay.
(DOCX)
Antibodies against biopharmaceuticals (anti-drug antibodies, ADA) have been a well-integrated part of the clinical care of multiple sclerosis (MS) in several European countries. ADA data generated in Europe during the more than 10 years of ADA monitoring in MS patients treated with interferon beta (IFNβ) and natalizumab have been pooled and charact...
Flow chart of quality control of the data.
(TIF)
Patient numbers and test information by preparation.
(DOCX)
Numbers of patients and median years to first test by preparation.
(DOCX)
Number of tests by patient age ranges.
(DOCX)
List of ABIRISK Consortium partners and members.
(DOCX)
Immunogenicity of biopharmaceutical products in multiple sclerosis is a frequent side effect which has a multifactorial etiology. Here we study associations between anti-drug antibody (ADA) occurrence and demographic and clinical factors. Retrospective data from routine ADA test laboratories in Sweden, Denmark, Austria and Germany (Dusseldorf group...
List of ABIRISK Consortium partners and members.
(DOCX)
Association of variables characterizing previous IFNβ therapy with anti-natalizumab ADA occurrence risk.
(TIF)
Anti-IFNβ ADA development hazard ratios with 95% confidence intervals for each month of birth (versus all the other months).
(DOCX)
Anti-IFNβ ADA development hazard ratios with 95% confidence intervals for each month of start of therapy (versus all the other months).
(DOCX)
Anti-natalizumab ADA development hazard ratios with 95% confidence intervals for each month of start of therapy (versus all the other months).
(DOCX)
Anti-natalizumab ADA development hazard ratios with 95% confidence intervals for each month of birth (versus all the other months).
(DOCX)
Comparison of the of the included to the excluded IFNβ-treated patients.
(DOCX)
Background
For clinical genomic studies with high-dimensional datasets, tree-based ensemble methods offer a powerful solution for variable selection and prediction taking into account the complex interrelationships between explanatory variables. One of the key component of the tree-building process is the splitting criterion. For survival data, the...
Introduction
En cancérologie, le développement des molécules cytostatiques a remis en cause le choix du critère de jugement dans l’évaluation de ces molécules en particulier en phase II. La réponse tumorale a été critiquée au profit de la survie sans progression (PFS). Cette dernière est un critère de jugement censuré qui nécessite des plans d’expé...
Intrahepatic cholangiocarcinomas (ICC) are relatively rare malignant tumors associated with a poor prognosis. Recent studies using genome-wide sequencing technologies have mainly focused on identifying new driver mutations. There is nevertheless a need to investigate the spectrum of copy number aberrations in order to identify potential target gene...
For phase II oncology trials, Simon's two-stage design is the most commonly used strategy. However, when clinically unevaluable patients occur, the total number of patients included at each stage differs from what was initially planned. Such situations raise concerns about the operating characteristics of the trial design. This paper evaluates thre...
In genomics, variable selection and prediction accounting for the complex interrelationships between explanatory variables represent major challenges. Tree-based methods are powerful alternatives to classical regression models. We have recently proposed the generalized, partially linear, tree-based regression (GPLTR) procedure that integrates the a...
Biopharmaceuticals (BPs) represent a rapidly growing class of approved and investigational drug therapies that is contributing significantly to advancing treatment in multiple disease areas, including inflammatory and autoimmune diseases, genetic deficiencies and cancer. Unfortunately, unwanted immunogenic responses to BPs, in particular those affe...
In randomized clinical trials where the times to event of two treatment groups are compared under a proportional hazards assumption, it has been established that omitting prognostic factors from the model entails an underestimation of the hazards ratio. Heterogeneity due to unobserved covariates in cancer patient populations is a concern since geno...
Non-small cell lung cancer (NSCLC) is a heterogeneous disease, with a burden of genomic alterations exceeding most other tumours. The goal of this study was to evaluate the frequencies of co-occurring mutations and copy-number aberrations (CNAs) within the same tumour and to evaluate their potential clinical impact. Mass-spectrometry based mutation...
Dissecting the genomic spectrum of clinical disease entities is a challenging task. Recursivepartitioning (or classification trees) methods provide powerful tools for exploring complex interplayamong genomic factors, with respect to a main factor, that can reveal hidden genomic patterns. Totake confounding variables into account, the partially line...
To identify genomic markers with consistent effect on tumor dynamics across multiple cancer series, discrimination indices based on proportional hazards models can be used since they do not depend heavily on the sample size. However, the underlying assumption of proportionality of the hazards does not always hold, especially when the studied popula...
Thymic carcinomas represent the rarest and the more aggressive form of thymic epithelial tumors. We retrospectively reviewed a series of 37 consecutive cases seen in our hospital over a 15-year period. The patient group consisted of 14 female and 23 male patients, aged 31 to 80 years (mean = 57). Nineteen patients were smokers (mean 29 PY). Two non...
Background
In early-stage of cancer, primary treatment can be considered as effective at eliminating the tumor for a non-negligible proportion of patients whereas for the others it leads to a lower tumor burden and thereby potentially prolonged survival. In this mixed population of patients, it is of great interest to detect complex differences in...
In clinical cancer research, high throughput genomic technologies are increasingly used to identify copy number aberrations. However, the admixture of tumor and stromal cells and the inherent karyotypic heterogeneity of most of the solid tumor samples make this task highly challenging. Here, we propose a robust two-step strategy to detect copy numb...
Despite similar morphological aspects, anaplastic oligodendroglial tumors (AOTs) form a heterogeneous clinical subgroup of gliomas. The chromosome arms 1p/19q codeletion has been shown to be a relevant biomarker in AOTs and to be perfectly exclusive from EGFR amplification in gliomas. To identify new genomic regions associated with prognosis, 60 AO...
![Figure 3. Univariate analysis. The test statistics [Àlog 10 (P)]...](profile/Lance-Miller-5/publication/51078602/figure/fig1/AS:601663584874519@1520459185683/Univariate-analysis-The-test-statistics-Alog-10-P-testing-the-null-hypothesis-of_Q320.jpg)
East-Asian (EA) patients with non-small-cell lung cancer (NSCLC) are associated with a high proportion of nonsmoking women, epidermal growth factor receptor (EGFR)-activating somatic mutations, and clinical responses to tyrosine kinase inhibitors. We sought to identify novel molecular differences between NSCLCs from EA and Western European (WE) pat...
Simulations results for , , and , for n = 100 subjects, and a uniform censoring (1,000 repetitions). Graphic: Boxplots of the different indices according to the values of eβ and pc.
Simulations results for , , and , for n = 100 subjects, and a uniform censoring (1,000 repetitions). Graphic: Boxplots of the different indices according to the values of eβ and pc.
Biological processes (obtained from the PANTHER classification system) for the lung cancer study cohort. Table: List of the biological process obtained according to and .
Lists of the cell cycle related transcripts among the selection according to the value of the index calculated either under the crossing hazards effect or the PH model. Tables: Lists of the cell cycle related transcripts according to and .
Abstract Background CXCL12 has been widely reported to play a biologically relevant role in tumor growth and spread. In epithelial ovarian cancer (EOC), CXCL12 enhances tumor angiogenesis and contributes to the immunosuppressive network. However, its prognostic significance remains unclear. We thus compared CXCL12 status in healthy and malignant ov...
In genomic medical studies, one of the major objectives is to identify genomic factors with a prognostic impact on time-to-event outcomes so as to provide new insights into the disease process. Selection usually relies on statistical univariate indices based on the Cox model. Such model assumes proportional hazards (PH) which is unlikely to hold fo...