A Study Of the effect of Sex on drug dosing, concentrations, and pharmacogenomics in the Montreal Heart Institute Hospital Cohort (SOS-PGx): methodology and research progress.

Background: Women are underrepresented in drug development trials and there is no sex-tailored drug regimen for most medications. It has been repeatedly shown that women have more adverse drug reactions than men for several medications. These differences could be explained by higher dose-adjusted drug concentrations in women.

Pharmacogenomic markers of metoprolol and α-OH-metoprolol concentrations: a genome-wide association study.

Few genome-wide association studies (GWASs) have been conducted to identify predictors of drug concentrations. The authors therefore sought to discover the pharmacogenomic markers involved in metoprolol pharmacokinetics. The authors performed a GWAS of a cross-sectional study of 993 patients from the Montreal Heart Institute Biobank taking metoprolol.

Interplay between hereditary and acquired factors determines the neutrophil counts in older individuals.

Blood cell production is a complex process, partly genetically determined and influenced by acquired factors. However, there is a paucity of data on how these factors interplay in the context of aging, which is associated with a myeloid proliferation bias, clonal hematopoiesis (CH), and an increased incidence of myeloid cancers. We investigated hereditary and acquired factors underlying blood cell trait variability in a cohort of 2996 related and unrelated women from Quebec aged from 55 to 101 years.

Pharmacogenomic study of heart failure and candesartan response from the CHARM programme.

Aims: The Candesartan in Heart failure Assessment of Reduction in Mortality and morbidity (CHARM) programme consisted of three parallel, randomized, double-blind clinical trials comparing candesartan with placebo in patients with heart failure (HF) categorized according to left ventricular ejection fraction and tolerability to an angiotensin-converting enzyme inhibitor. We conducted a pharmacogenomic study of the CHARM trials with the objective of identifying genetic predictors of HF progression and of the efficacy and safety of treatment with candesartan.

Methods: We performed genome-wide association studies in 2727 patients of European ancestry from CHARM-Overall and stratified by CHARM study according to preserved and reduced ejection fraction and according to assignment to the interventional treatment with candesartan.

Genetics of symptom remission in outpatients with COVID-19.

We conducted a genome-wide association study of time to remission of COVID-19 symptoms in 1723 outpatients with at least one risk factor for disease severity from the COLCORONA clinical trial. We found a significant association at 5p13.3 (rs1173773; P = 4.

Genetic meta-analysis of cancer diagnosis following statin use identifies new associations and implicates human leukocyte antigen (HLA) in women.

We sought to perform a genomic evaluation of the risk of incident cancer in statin users, free of cancer at study entry. Patients who previously participated in two phase IV trials (TNT and IDEAL) with genetic data were used (n = 11,196). A GWAS meta-analysis using Cox modeling for the prediction of incident cancer was conducted in the pooled cohort and sex-stratified.

Pharmacogenomics of the Efficacy and Safety of Colchicine in COLCOT.

Background: The randomized, placebo-controlled COLCOT (Colchicine Cardiovascular Outcomes Trial) has shown the benefits of colchicine 0.5 mg daily to lower the rate of ischemic cardiovascular events in patients with a recent myocardial infarction. Here, we conducted a post hoc pharmacogenomic study of COLCOT with the aim to identify genetic predictors of the efficacy and safety of treatment with colchicine.

A genetic association study of heart failure: more evidence for the role of BAG3 in idiopathic dilated cardiomyopathy.

Aims: Few investigations have been conducted to identify genetic determinants of common, polygenetic forms of heart failure (HF), and only a limited number of these genetic associations have been validated by multiple groups.

Methods And Results: We performed a case-control study to further investigate the potential impact of 14 previously reported candidate genes on the risk of HF and specific HF sub-types. We also performed an exploratory genome-wide study.

A genetic model of ivabradine recapitulates results from randomized clinical trials.

Background: Naturally occurring human genetic variants provide a valuable tool to identify drug targets and guide drug prioritization and clinical trial design. Ivabradine is a heart rate lowering drug with protective effects on heart failure despite increasing the risk of atrial fibrillation. In patients with coronary artery disease without heart failure, the drug does not protect against major cardiovascular adverse events prompting questions about the ability of genetics to have predicted those effects.

The Impact of Team-Based Primary Care on Guideline-Recommended Disease Screening.

Introduction: Family Medicine Groups, implemented in Quebec in 2002, are interprofessional primary care teams designed to improve timely access to high-quality primary care. This study investigates whether Family Medicine Groups increased rates of guideline-recommended screenings for 3 chronic diseases: colorectal cancer (colonoscopy/sigmoidoscopy), breast cancer (mammography), and osteoporosis (bone mineral density testing).

Methods: Using population-based administrative health data from the provincial insurer (2000-2010), the authors examined elderly and chronically ill patients who registered with a general practitioner in the first 15 months of the Family Medicine Group policy.

rs73185306 C/T Is Not a Predisposing Risk Factor for Inherited Chromosomally Integrated Human Herpesvirus 6A/B.

Approximately 1% of people worldwide carry a copy of the human herpesvirus 6A or 6B (HHV-6A/B) in every cell of their body. This condition is referred to as inherited chromosomally integrated HHV-6A/B (iciHHV-6A/B). The mechanisms leading to iciHHV-6A/B chromosomal integration are yet to be identified.

Chronic disease prevention and management programs in primary care: Realist synthesis of 6 programs in Quebec.

Objective: To identify the mechanisms associated with success and failure of chronic disease prevention and management (CDPM) programs, as well as their key contexts.

Design: Realist synthesis.

Setting: Six primary care CDPM programs funded between 2011 and 2013 in Quebec.

Lineage restriction analyses in CHIP indicate myeloid bias for and multipotent stem cell origin for .

We analyzed DNA from polymorphonuclear (PMN) cells, monocytes, B cells, and T cells of 107 individuals with clonal hematopoiesis of indeterminate potential (CHIP) to perform lineage restriction analysis of different gene mutations. Three lineage categories were defined: myeloid (PMN with or without monocytes), myelolympho-B (myeloid and B cells), and multipotent (myeloid, B and T cells). Six individuals with aberrant patterns were excluded from analysis.

A prospective study of the impact of AGTR1 A1166C on the effects of candesartan in patients with heart failure.

Aim: To evaluate the impact of AGTR1 A1166C (rs5186) on the response to candesartan in patients with heart failure.

Materials & Methods: Prospective, multicentre, open-label study. We studied 299 symptomatic patients with heart failure presenting a left ventricular ejection fraction ≤40%.

Rationale, design, and preliminary results of the Quebec Warfarin Cohort Study.

Over- and undercoagulation with warfarin are associated with hemorrhagic and thromboembolic events, respectively. Genetic and clinical factors affect warfarin response, and the causes of this variability remain unclear. We present descriptive statistics and test for predictors of poor anticoagulation control.

Effects on patients of variations in the implementation of a cardiometabolic risk intervention program in Montréal.

Introduction: In 2011, the Agence de la santé et des services sociaux de Montréal (ASSSM), in partnership with the region's Centres de santé et de services sociaux (CSSS), coordinated the implementation of a program on cardiometabolic risk based on the Chronic Care Model. The program, intended for patients suffering from diabetes or hypertension, involved a series of individual follow-up appointments, group classes and exercise sessions. Our study assesses the impact on patient health outcomes of variations in the implementation of some aspects of the program among the six CSSSs taking part in the study.

Nuclear receptor gene polymorphisms and warfarin dose requirements in the Quebec Warfarin Cohort.

Warfarin is primarily metabolized by cytochrome 2C9, encoded by gene CYP2C9. Here, we investigated whether variants in nuclear receptor genes which regulate the expression of CYP2C9 are associated with warfarin response. We used data from 906 warfarin users from the Quebec Warfarin Cohort (QWC) and tested the association of warfarin dose requirement at 3 months following the initiation of therapy in nine nuclear receptor genes: NR1I3, NR1I2, NR3C1, ESR1, GATA4, RXRA, VDR, CEBPA, and HNF4A.

Identification of the genetic determinants responsible for retinal degeneration in families of Mexican descent.

Purpose: To investigate the clinical characteristics and genetic basis of inherited retinal degeneration (IRD) in six unrelated pedigrees from Mexico.

Methods: A complete ophthalmic evaluation including measurement of visual acuities, Goldman kinetic or Humphrey dynamic perimetry, Amsler test, fundus photography, and color vision testing was performed. Family history and blood samples were collected from available family members.

What can organizations do to improve family physicians' interprofessional collaboration? Results of a survey of primary care in Quebec.

Objective: To assess the degree of collaboration in primary health care organizations between FPs and other health care professionals; and to identify organizational factors associated with such collaboration.

Design: Cross-sectional survey.

Setting: Primary health care organizations in the Montreal and Monteregie regions of Quebec.

Explaining time elapsed prior to cancer diagnosis: patients' perspectives.

Background: Cancer is the leading cause of death in Canada. Early cancer diagnosis could improve patients' prognosis and quality of life. This study aimed to analyze the factors influencing elapsed time between the first help-seeking trigger and cancer diagnosis with respect to the three most common and deadliest cancer types: lung, breast, and colorectal.

and dominate clonal hematopoiesis and demonstrate benign phenotypes and different genetic predispositions.

Age-associated clonal hematopoiesis caused by acquired mutations in myeloid cancer-associated genes is highly prevalent in the normal population. Its etiology, biological impact on hematopoiesis, and oncogenic risk is poorly defined at this time. To gain insight into this phenomenon, we analyzed a cohort of 2530 related and unrelated hematologically normal individuals (ages 55 to 101 years).