Aging, Author Interviews, Genetic Research, McGill / 22.11.2020

MedicalResearch.com Interview with: Richard C. Austin, PhD Professor and Career Investigator of the Heart and Stroke Foundation of Ontario Amgen Canada Research Chair in Nephrology McMaster University and St. Joseph’s Healthcare Hamilton, Ontario, Canada MedicalResearch.com: What is the background for this study? What are the main findings? Response: A previous study published in 2011 by my collaborator, Dr. Michel Chretien at the IRCM, identified a rare mutation in the PCSK9, termed Q152H. Individuals harboring this mutation demonstrated dramatic reductions in their LDL cholesterol levels and had a significantly lower risk of CVD. Furthermore, individuals harboring the Q152H mutation showed increases in longevity with no evidence of other diseases such as liver disease, cancer and chronic kidney disease. This Q152H mutation was unique with only 4 families in Quebec shown to harbor this genetic variant. In terms of its effect on PCSK9 expression/activity, the mutation at Q152H was precisely at the cleavage site in PCSK9 necessary for its activation. As a result, the Q152H mutation fails to be cleaved and activated, thereby blocking its secretion into the circulation. This is why the Q152H mutation is considered a loss-of-function PCSK9 mutant. Given our lab's interest in endoplasmic reticulum (ER) stress and ER storage diseases, we began to collaborate with Drs. Chretien and Seidah at the IRCM to investigate whether this Q152H mutant, when overexpressed in liver cells, would cause ER stress and liver cell injury. This was based on the findings that the Q152H mutant does not undergo autocatalytic cleavage and its subsequent secretion from liver cells. It is well known in the literature that the accumulation of misfolded or inactive proteins in the ER gives rise to ER stress and cell injury/dysfunction. As a result, we initially showed to our surprise that overexpression of the Q152H mutant in liver cells failed to cause ER stress BUT increased the protein levels of several important ER chaperones, GRP78 and GRP94, known to PROTECT against liver cell injury/dysfunction. As part of our JCI study, we furthered these studies to examine the effect of the Q152H mutant when overexpressed in the livers of mice. This is where we demonstrated that the Q152H mutation showed protection against ER stress-induced liver injury/dysfunction. (more…)
Author Interviews, Brigham & Women's - Harvard, JAMA, Prostate Cancer, Social Issues / 18.11.2020

MedicalResearch.com Interview with: David-Dan Nguyen, MPH Research Fellow | Center for Surgery and Public Health Brigham and Women's Hospital Medical Student | McGill University  MedicalResearch.com: What is the background for this study? Response: In 2017, the US Preventive Services Task Force updated its recommendation for PSA screening for prostate cancer from a grade D to a grade C for men aged 55 to 69 years. This updated recommendation endorsed shared decision making and harmonizes with the guidelines of the American Urological Association and the American Cancer Society which also recommend shared decision making for PSA screening. Shared decision making is a meaningful dialogue between the physician and the patient that namely includes a review of risks and expected outcomes of screening as well as the patient’s preferences and values. Understandably, the patient’s ability to critically assess the medical information provided (i.e. their health literacy) likely influences this process. We sought to characterize the effect of health literacy on shared decision making for PSA screening. We used data from 2016 when PSA screening for prostate cancer was not recommended by the US Preventive Services Task Force — in other words, we also sought to understand how health literacy impacted screening rates in the context of countervailing guidelines on PSA screening. (more…)
Author Interviews, Hospital Acquired, JAMA / 20.08.2019

MedicalResearch.com Interview with: Todd Campbell Lee MD MPH FACP FIDSA Consultant in Internal Medicine and Infectious Diseases Director, MI4 Clinical Trials Platform Associate Professor of Medicine, McGill University Montreal, Quebec  MedicalResearch.com: What is the background for this study? Response: For a number of years people have been advocating for a move towards single-patient rooms in hospital design.  This was articulately argued for in an opinion piece by Detsky and Etchells in 2008 (https://jamanetwork.com/journals/jama/article-abstract/182433) as being important for a move to safe and patient-centered design. One of the major selling points has always been a reduction in the risk of nosocomial, or hospital-associated, infections given reduced opportunities for contamination between patients; however, only a few studies have specifically looked at this issue.  Overall, despite some strong work, many of these studies were limited by only looking at specific units, over limited periods of time,  and using before-after comparisons which did not account for change over time either within or outside of the institution. We knew that in 2015 our old hospital would close and within the same day all patients would be moved to a brand new hospital with 100% single patient rooms -- most of which have a private bathroom for patients and a separate hand-washing sink for staff.  So in 2014, we designed this study, obtained ethics review, and then waited patiently for several years to pass after the move so that we could rigorously evaluate the impact.  We looked at monthly rates of vancomycin-resistant Enterococcus (VRE) colonizations and infections, methicillin-resistant Staphylococcus aureus (MRSA) colonization and infections, and Clostridium (now Clostrideroidesdifficile infections (CDI). We chose these because we had good long term data on their rates and because we could compare the rates over time before and after the move and contrast them with the province of Quebec as a whole. (more…)
Author Interviews, McGill, Multiple Sclerosis, Neurology / 09.05.2019

MedicalResearch.com Interview with: Douglas Arnold, MD The Montreal Neurological Institute & Hospital McGill University Montreal, QC, Canada MedicalResearch.com: What is the background for this study? Response: Diroximel fumarate (DRF) is a novel oral fumarate, with a distinct chemical structure that is being developed for relapsing forms of multiple sclerosis (MS). It is hypothesized that the distinct chemical structure of DRF may elicit less localized irritation in the gastrointestinal (GI) tract, potentially leading to improved GI tolerability. Diroximel fumarate is expected to have similar efficacy as dimethyl fumarate (marketed as TECFIDERA®), as both are converted to equivalent levels of monomethyl fumarate in the body. The EVOLVE-MS-1 study is primarily evaluating the safety of DRF and also exploring efficacy endpoints.   (more…)