Mireille E. Schnitzer's research while affiliated with Polytechnique Montréal and other places
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Publications (90)
Cox models with time-dependent coefficients and covariates are widely used in survival analysis. In high-dimensional settings, sparse regularization techniques are employed for variable selection, but existing methods for time-dependent Cox models lack flexibility in enforcing specific sparsity patterns (i.e., covariate structures). We propose a fl...
Heart failure (HF) is associated with morbidity, rehospitalization and polypharmacy. The incidence rate of mortality in HF patients with polypharmacy is poorly studied. We examine the association of polypharmacy with mortality risk in incident hospitalized HF patients with a primary diagnosis after discharge from the hospital using Quebec administr...
Approximate statistical inference via determination of the asymptotic distribution of a statistic is routinely used for inference in applied medical statistics (e.g. to estimate the standard error of the marginal or conditional risk ratio). One method for variance estimation is the classical Delta-method but there is a knowledge gap as this method...
Predictor identification is important in medical research as it can help clinicians to have a better understanding of disease epidemiology and identify patients at higher risk of an outcome. Variable selection is often used to reduce the dimensionality of a prediction model. When conducting variable selection, it is often beneficial to take selecti...
Background
Tools capable of predicting the risk of asthma exacerbations can facilitate asthma management in clinical practice. However, existing tools require additional data from patients beyond electronic medical records.
Objective
To predict asthma exacerbation in an upcoming year using electronically accessible data conditional on past adheren...
The test-negative design is routinely used for the monitoring of seasonal flu vaccine effectiveness. More recently, it has become integral to the estimation of COVID-19 vaccine effectiveness, in particular for more severe disease outcomes. Because the design has many important advantages and is becoming a mainstay for monitoring postlicensure vacci...
The p75 NTR receptor binds all neurotrophins and is mostly known for its role in neuronal survival and apoptosis. Recently, the extracellular domain (ECD) of p75 NTR has been reported in plasma, its levels being dysregulated in numerous neurological diseases. However, the factors associated with p75 NTR ECD levels remain unknown. We investigated cl...
Background
We expect a difference in drug cost between private drug plans and the Public Drug Plan (PDP) because the dispensing fee is fixed and regulated by the PDP for publicly insured patients, whereas it is determined freely by the pharmacy owner for privately insured patients. This study compared the drug cost of Quebec residents covered by pr...
![FIGURE 3 | Hazard ratios [95%CI] for comparisons between low-dose DOACs...](publication/357865489/figure/fig2/AS:1113086568214529@1642391926760/Hazard-ratios-95CI-for-comparisons-between-low-dose-DOACs-in-an-as-treated-analysis_Q320.jpg)
Aims: Observational studies of various dose levels of direct oral anticoagulants (DOACs) for patients with atrial fibrillation (AF) found that a high proportion of patients received a dose lower than the target dose tested in randomized controlled trials. There is a need to compare low-dose DOACs with warfarin or other DOACs on effectiveness and sa...
Many studies seek to evaluate the effects of potentially harmful pregnancy exposures during specific gestational periods. We consider an observational pregnancy cohort where pregnant individuals can initiate medication usage or become exposed to a drug at various times during their pregnancy. An important statistical challenge involves how to defin...
Effect modification occurs when the effect of a treatment on an outcome differsaccording to the level of some pre-treatment variable (the effect modifier). Assessing an effect modifier is not a straight-forward task even for a subject matter expert. In this paper, we propose a two-stageprocedure to automatically selecteffect modifying variables in...
Purpose:
Confounding adjustment is required to estimate the effect of an exposure on an outcome in observational studies. However, variable selection and unmeasured confounding are particularly challenging when analyzing large healthcare data. Machine learning methods may help address these challenges. The objective was to evaluate the capacity of...
Effect modification occurs while the effect of the treatment is not homogeneous across the different strata of patient characteristics. When the effect of treatment may vary from individual to individual, precision medicine can be improved by identifying patient covariates to estimate the size and direction of the effect at the individual level. Ho...
Variable selection is commonly used to arrive at a parsimonious model when relating an outcome to high-dimensional covariates. Oftentimes a selection rule that prescribes the permissible variable combinations in the final model is desirable due to the inherent structural constraints among the candidate variables. Penalized regression methods can in...
Background:
Despite availability of effective antiretroviral therapy (ART) many HIV patients still have a detectable viral load (VL). Predictive factors of detectable VL are not well documented. This study was done at two large multidisciplinary HIV outpatient clinics at the Centre hospitalier de l'Université de Montréal (CHUM) and the McGill Univ...
Objective
To determine whether new users of proton pump inhibitors (PPIs) are at an increased risk of gastric cancer compared with new users of histamine-2 receptor antagonists (H2RAs).
Design
Using the UK Clinical Practice Research Datalink, we conducted a population-based cohort study using a new-user active comparator design. From 1 January 199...
Objective
To determine whether proton pump inhibitors (PPIs) are associated with an increased risk of colorectal cancer, compared with histamine-2 receptor antagonists (H2RAs).
Design
The United Kingdom Clinical Practice Research Datalink was used to identify initiators of PPIs and H2RA from 1990 to 2018, with follow-up until 2019. Cox proportiona...
Owing to the rapidly evolving coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, quick public health investigations of the relationships between behaviors and infection risk are essential. Recently the test-negative design (TND) was proposed to recruit and survey participan...
Inverse probability of censoring weights (IPCWs) may reduce selection bias due to informative censoring in longitudinal studies. However, in studies with an active comparator, the associations between predictors and censoring may differ across treatment groups. We used the clinical example of anticoagulation treatment with warfarin or a direct oral...
Objectives:
We aimed to test the hypothesis that exposure to immunosuppression in early systemic sclerosis (SSc) could modify the risk of developing new onset severe gastrointestinal (GIT) involvement.
Methods:
A total of 762 subjects with <3 years of disease duration and without severe GIT disease at baseline study visit were identified from co...
http://arxiv.org/abs/2103.15218
Administrative data, or non-probability sample data, are increasingly being used to obtain official statistics due to their many benefits over survey methods. In particular, they are less costly, provide a larger sample size, and are not reliant on the response rate. However, it is difficult to obtain an unbiased estimate of the population mean fro...
Aim:
Real-world predictors of major bleeding (MB) have been well-studied among warfarin users, but not among all direct oral anticoagulant (DOAC) users diagnosed with atrial fibrillation (AF). Thus, our goal was to build a predictive model of MB for new users of all oral anticoagulants (OAC) with AF.
Methods:
We identified patients hospitalized...
Purpose
: We assessed whether the protective association between hyperemesis gravidarum and birth defects could be due to selection bias from exclusion of pregnancy terminations.
Methods
: We designed a cohort study of 2,115,581 live births in Canada, 1990-2016. The main exposure measure was hyperemesis gravidarum. The main outcome measure include...
Background:
Observational studies assessing direct oral anticoagulant (DOACs) dosage in atrial fibrillation (AF) reported that a lower proportion of patients received high-dose DOACs compared to those in randomized controlled trials (RCTs). Effectiveness and safety of high-dose DOACs relative to apixaban in a real-world AF population needs to be a...
Effect modification occurs while the effect of the treatment is not homogeneous across the different strata of patient characteristics. When the effect of treatment may vary from individual to individual, precision medicine can be improved by identifying patient covariates to estimate the size and direction of the effect at the individual level. Ho...
Purpose
The purpose of this study was to examine whether the latest National Institute for Health and Care Excellence proton pump inhibitor (PPI) guidelines changed physician prescribing patterns in clinical practice.
Methods
Using data from the United Kingdom Clinical Practice Research Datalink, we calculated monthly PPI prescribing rates in adul...
Objective
To examine proton pump inhibitor (PPI) and histamine-2 receptor antagonist (H2RA) prescribing patterns over a 29-year period by quantifying annual prevalence and prescribing intensity over time.
Design
Population-based cross-sectional study.
Setting
More than 700 general practices contributing data to the UK Clinical Practice Research D...
Aims:
There are conflicting signals in the literature about comparative safety and effectiveness of direct oral anticoagulants (DOACs) for nonvalvular atrial fibrillation (NVAF).
Methods:
We conducted multicentre matched cohort studies with secondary meta-analysis to assess safety and effectiveness of dabigatran, rivaroxaban and apixaban across...
Effect modification occurs when the effect of the treatment on an outcome differs according to the level of a third variable (the effect modifier, EM). A natural way to assess effect modification is by subgroup analysis or include the interaction terms between the treatment and the covariates in an outcome regression. The latter, however, does not...
Background:
Direct oral anticoagulants (DOACs) have widely replaced warfarin for stroke prevention in nonvalvular atrial fibrillation. Our objective was to compare the safety and effectiveness of DOACs (dabigatran, rivaroxaban, apixaban) versus warfarin for stroke prevention in nonvalvular atrial fibrillation in the Canadian setting.
Methods:
We...
Background
Switching antiretroviral regimens when HIV viremia is controlled for a new regimen is challenging when there is the potential for prior nucleoside reverse transcriptase inhibitor (NRTI) resistance. The objective was to study virologic outcomes after switching to dolutegravir compared to remaining on a boosted protease inhibitor (PI/r) re...
In longitudinal settings, causal inference methods usually rely on a discretization of the patient timeline that may not reflect the underlying data generation process. This article investigates the estimation of causal parameters under discretized data. It presents the implicit assumptions practitioners make but do not acknowledge when discretizin...
In this tutorial, we focus on the problem of how to define and estimate treatment effects when some patients develop a contraindication and are thus ineligible to receive a treatment of interest during follow‐up. We first describe the concept of positivity, which is the requirement that all subjects in an analysis be eligible for all treatments of...
Due to the rapidly evolving COVID-19 pandemic caused by the SARS-CoV-2 virus, quick public health investigations of the relationships between behaviours and infection risk are essential. Recently the test-negative design was proposed to recruit and survey participants who are being tested for SARS-CoV-2 infection in order to evaluate associations b...
Background:
The link between mood disorders and cardiovascular disease in women is unclear. We studied the association of mood disorders around pregnancy with the future risk of cardiovascular disease.
Methods:
We analyzed a cohort of 1,028,109 women who were pregnant between 1989 and 2012 in Quebec, Canada. We identified women hospitalized for...
Women who deliver preterm are at risk of cardiovascular disease, but the reason for the association is unclear. We determined whether vascular disorders during pregnancy explain the association between preterm delivery and future maternal cardiovascular disease. We analyzed a longitudinal cohort of 1 199 364 pregnant women with 19 186 983 person-ye...
Background:
It is unclear if asthma diagnosed during pregnancy puts the fetus at a higher risk of poor perinatal outcomes than pre-existing asthma.
Objective:
To assess if the risks of prematurity, major malformations, and small-for-gestational age (SGA) are higher in women with asthma diagnosed during versus pre-pregnancy.
Methods:
We retrosp...
Persons with multidrug-resistant tuberculosis (MDR-TB) have a disease resulting from a strain of tuberculosis (TB) that does not respond to at least isoniazid and rifampicin, the two most effective anti-TB drugs. MDR-TB is always treated with multiple antimicrobial agents. Our data consist of individual patient data from 31 international observatio...
Background and purpose:
Data on oral anticoagulant (OAC) uptake and pattern of use is limited. Real-life data in patients with atrial fibrillation (AF) is important for understanding patient exposure. A cohort study of new OAC users was built to assess trends of drug use from 2011 to 2017, persistence rate, switching rate, adherence level, and pre...
Objective:
Data from rigorous evaluations of the impact of interventions on improving surgical antibiotic prophylaxis (SAP) compliance in pediatrics are lacking. Our objective was to assess the impact of a multifaceted intervention on improving pediatric SAP compliance in a hospital without an ongoing antimicrobial stewardship program.
Study desi...
Properly interpreting research results is the foundation of evidence-based medicine. Most observational studies use multiple regression and report adjusted effects. In randomised trials, adjusted effects are often provided when there are chance baseline imbalances. The estimates for the exposure of interest (eg, treatment) from these adjusted analy...
Causal inference methods have been developed for longitudinal observational study designs where confounding is thought to occur over time. In particular, one may estimate and contrast the population mean counterfactual outcome under specific exposure patterns. In such contexts, confounders of the longitudinal treatment‐outcome association are gener...
Background:
Despite the increasing use of medical records to measure quality of care, studies have shown that their validity is suboptimal. The objective of this study is to assess the concordance of cardiovascular care processes evaluated through medical record review and patient self-administered questionnaires (SAQs) using ten quality indicator...
Background and purpose:
Patients with nonvalvular atrial fibrillation (NVAF) who survive an intracranial hemorrhage (ICH) have an increased risk of ischemic stroke and systemic embolism (IS/ SE). We investigated whether starting oral anticoagulants (OACs) among older NVAF patients after an ICH was associated with a lower risk of IS/SE and mortalit...
Background:
Colorectal cancer screening participation is lower among recent immigrants than among Canadian-born individuals. We assessed whether this screening disparity is mediated by access to regular primary care physicians (PCP).
Methods:
Pooling years 2003 to 2014 of the Canadian Community Health Survey, lifetime screening in respondents ag...
Classical epidemiology has focused on the control of confounding, but it is only recently that epidemiologists have started to focus on the bias produced by colliders. A collider for a certain pair of variables (e.g. an outcome Y and an exposure A) is a third variable (C) that is caused by both. In a directed acyclic graph (DAG), a collider is the...
Background:
Cardiovascular disease morbidity and mortality are largely influenced by poor control of hypertension, dyslipidemia, and diabetes. Process indicators are essential to monitor the effectiveness of quality improvement strategies. However, process indicators should be validated by demonstrating their ability to predict desirable outcomes....
This paper investigates different approaches for causal estimation under multiple concurrent medications. Our parameter of interest is the marginal mean counterfactual outcome under different combinations of medications. We explore parametric and non-parametric methods to estimate the generalized propensity score. We then apply three causal estimat...
Thrombocytopenia (TP) is common in hospitalized patients. In the context of acute coronary syndromes (ACS), TP has been linked to adverse clinical outcomes. We present a systematic review and meta-analysis of the evidence on the clinical importance of preexisting and in-hospital acquired TP in the context of ACS. Specifically, we address (a) the pr...
Electronic health data are routinely used for population drug studies. Due to the ethical dilemma in carrying out experimental drug studies on pregnant women, the effects of medication usage during pregnancy on fetal and maternal outcomes are largely evaluated using this data collection medium. One major limitation in this type of study is the dela...
Classical epidemiology has focused on the control of confounding but it is only recently that epidemiologists have started to focus on the bias produced by colliders. A collider for a certain pair of variables (e.g., an outcome Y and an exposure A) is a third variable (C) that is caused by both. In DAGs terminology, a collider is the variable in th...
This study examined the associations between the context in which physical activity (PA) is undertaken (team sports, informal group, individual PA), and each of positive mental health, anxiety symptoms and depressive symptoms. It also investigated whether social connectedness or PA volume mediate these associations. A total of 460 students (62.4% f...
Purpose: To assess the pregnancy outcomes of women with spina bifida.
Materials and methods: We analyzed a population-based cohort of 397 pregnant women with spina bifida and 1,083,211 without spina bifida who delivered infants in hospitals in Quebec, Canada, 1989-2013. Outcomes included maternal and infant morbidity and mortality at delivery. We u...
Causal inference practitioners are routinely presented with the challenge of model selection and, in particular, reducing the size of the covariate set with the goal of improving estimation efficiency. Collaborative targeted minimum loss-based estimation (CTMLE) is a general framework for constructing doubly robust semiparametric causal estimators...
Background
No study to date has rigorously assessed the impact of interventions on improving surgical antibiotic prophylaxis (SAP) compliance in pediatrics. Our study is the first to adequately evaluate the timing criterion and to evaluate the persistence of compliance following the discontinuation of active interventions. Our objective was to asse...
The intention-to-treat analysis evaluates the causal effect of treatment assignment in a randomized controlled trial; however, participants do not always adhere to assigned treatment and the intention to treat effect may differ from the effect of treatment receipt. Although more recent adherence-based methods assess a well-defined causal effect of...
Objective: The objective of this study was to identify biopsychosocial factors predicting primary care chronic non-cancer pain (CNCP) patients’ risk of being heavy health care users.
Methods: Patients reporting moderate to severe CNCP for at least 6 months with an active analgesic prescription from a primary care physician were recruited in communi...
The role of pharmacists in HIV outpatient clinics has greatly increased in the past decades. Given the limited resources of the health system, the prioritization of pharmacist consults is now a main concern. This study aimed to create a scoring system allowing for standardized prioritization of pharmacist consults for patients living with HIV. Data...
When estimating the average effect of a binary treatment (or exposure) on an outcome, methods that incorporate propensity scores, the G‐formula, or targeted maximum likelihood estimation (TMLE) are preferred over naïve regression approaches, which are biased under misspecification of a parametric outcome model. In contrast propensity score methods...
Background: The aim of this systematic review and meta-analysis was to consider the evidence on the clinical importance of baseline or in-hospital acquired thrombocytopenia (TP) in the context of an acute coronary syndrome (ACS). This was split into two research questions: What is the frequency and associated factors with TP in the context of ACS?...
Inverse probability of treatment weighting (IPW) and targeted maximum likelihood estimation (TMLE) are relatively new methods proposed for estimating marginal causal effects. TMLE is doubly robust, yielding consistent estimators even under misspecification of either the treatment or the outcome model. While IPW methods are known to be sensitive to...
While standard meta-analysis pools the results from randomized trials that compare two treatments, network meta-analysis aggregates the results of randomized trials comparing a wider variety of treatment options. However, it is unclear whether the aggregation of effect estimates across heterogeneous populations will be consistent for a meaningful p...
Objective
To determine the association between recurrent pre-eclampsia and long-term cardiovascular hospitalisation.
Methods
This study identified cardiovascular hospitalisations up to 25 years after pregnancy for all women who delivered between 1989 and 2013 in Québec, Canada. Exposures included recurrent and non-recurrent pre-eclampsia in women...
Social epidemiologists often seek to determine the mechanisms that underlie health disparities. This work is typically based on mediation procedures that may not be justified with exposures of common interest in social epidemiology. In this analysis, we explored the consequences of using standard approaches, referred to as the difference and genera...
Objective: To determine the association between recurrent preeclampsia and long term cardiovascular hospitalization.
Methods: This study identified cardiovascular hospitalizations up to 25 years after pregnancy for all women who delivered between 1989-2013 in Quebec, Canada. Exposures included recurrent and nonrecurrent preeclampsia in women with t...
This paper investigates the appropriateness of the integration of flexible propensity score modeling (nonparametric or machine learning approaches) in semiparametric models for the estimation of a causal quantity, such as the mean outcome under treatment. We begin with an overview of some of the issues involved in knowledge-based and statistical va...
In longitudinal data arising from observational or experimental studies, dependent subject drop-out is a common occurrence. If the goal is estimation of the parameters of a marginal complete-data model for the outcome, biased inference will result from fitting the model of interest with only uncensored subjects. For example, investigators are inter...
While standard meta-analysis pools the results from randomized trials that
compare two specific treatments, network meta-analysis aggregates the results
of randomized trials comparing a wider variety of treatment options. However,
it is unclear whether the aggregation of effect estimates across heterogeneous
populations will be consistent for a mea...
The PROmotion of Breastfeeding Intervention Trial (PROBIT) cluster-randomized
a program encouraging breastfeeding to new mothers in hospital centers. The
original studies indicated that this intervention successfully increased
duration of breastfeeding and lowered rates of gastrointestinal tract
infections in newborns. Additional scientific and pop...
Despite modern effective HIV treatment, hepatitis C virus (HCV) co-infection is associated with a high risk of progression to end-stage liver disease (ESLD) which has emerged as the primary cause of death in this population. Clinical interest lies in determining the impact of clearance of HCV on risk for ESLD. In this case study, we examine whether...
Targeted maximum likelihood methods have been proposed to estimate treatment effects for longitudinal data in the presence
of time-dependent confounders. This class of methods has been mathematically proven to be doubly robust and to optimize the
asymptotic estimating efficiency among the class of regular, semi-parametric estimators when all estima...