Metformin Reverses Some Autism Symptoms In Animal Model

MedicalResearch.com Interview with:
Ilse Gantois, PhD

Research Associate
Dr. Nahum Sonenberg’s laboratory
Department of Biochemistry
McGill University

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Fragile X syndrome (FXS) is a neurodevelopmental disorder characterized by cognitive impairment and affects 1 in 4000 males and 1 in 6000 females. About 60% of persons with Fragile X also have autism spectrum disorder. FXS is caused by absence of Fragile X protein (FMRP), which results in hyperactivation of ERK (extracellular signal-regulated kinase) and mTORC1 (mechanistic target of rapamycin complex 1) signaling. We show that treatment with metformin, the most widely used FDA-approved antidiabetic drug, suppresses translation by inhibiting the ERK pathway, and alleviates a variety of behavioural deficits, including impaired social interaction and excessive grooming. In addition, metformin also reversed defects in dendritic spine morphogenesis and synaptic transmission.
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Recreational Cocaine Use Activates Addiction Related Brain Mechanisms Sooner Than Previously Realized

MedicalResearch.com Interview with:

Marco Leyton, Ph.D. Professor, Department of Psychiatry McGill University

Dr. Marco Leyton

Marco Leyton, Ph.D.
Professor, Department of Psychiatry
McGill University

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Drug-related cues are potent triggers for eliciting conscious and unconscious desire for the drug. In people with severe substance use disorders, these cues also activate dopamine release in the dorsal striatum, a brain region thought to be involved in hard-to-break habits and compulsions.

In the present study we found evidence that drug cues also activate this same dopamine response in non-dependent ‘recreational’ cocaine users.

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Strong SSRIs Linked To Increase Risk of Intracranial Hemorrhage

MedicalResearch.com Interview with:
Christel Renoux, MD, PhD
Assistant Professor, Dept. of Neurology & Neurosurgery
McGill University
Centre For Clinical Epidemiology
Jewish General Hospital – Lady Davis Research Institute
Montreal  Canada

MedicalResearch.com: What is the background for this study?

Response: Selective serotonin reuptake inhibitors (SSRIs) increase the risk for abnormal bleeding, in particular, gastrointestinal tract bleeding. Previous studies also suggested an increased risk for intracranial hemorrhage (ICH) in patients treated with SSRIs compared to non users. However, even if this risk exists, the comparison with a non-treated group may exaggerate the strength of a potential association and the comparison with a group of patients treated with other antidepressants may help better delineate the risk. The potential bleeding effect of antidepressants is linked to the strength of serotonin inhibition reuptake, and antidepressants that are strong inhibitors of serotonin reuptake have been associated with the risk for gastrointestinal or abnormal bleeding compared with weak inhibitors but the risk of ICH is unclear.

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Analysis of Multiple MRI and PET Images Detects Earliest Signs of Alzheimer’s Disease

MedicalResearch.com Interview with:

Dr. Yasser Iturria Medina PhD Post-doctoral fellow Montreal Neurological Institute

Dr. Y. M. Medina

Dr. Yasser Iturria Medina PhD
Post-doctoral fellow
Montreal Neurological Institute

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: We used over 200 peripheral molecular biomarkers, five different neuroimaging modalities and cognitive/clinical measurements to detect spatiotemporal abnormalities in subjects with dementia or with mild signs of cognitive deterioration. By means of a mathematical framework, we reordered all the biomarkers/descriptors considered, according to how much they change during the disease process. The results suggested that, contrary as suggested by more traditional clinical analyses, there are multiple early signs of neurodegeneration, at the molecular level and at the brain’s macroscopic and cognitive state. In particular, we observed notable early signs of generalized vascular dysregulation, which may be supporting the vascular hypothesis of Alzheimer’s disease. However, we still need to perform deeper analyzes, in order to clarify the complex causal mechanisms that trigger the disease.

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Isolating Asymptomatic C. diff Carriers at Hospital Admission May Decrease Transmission

MedicalResearch.com Interview with:
Yves Longtin, MD, FRCPC
Chair, Infection Prevention and Control Unit
Montreal Jewish General Hospital – SMBD
Associate professor of Medicine, McGill University

MedicalResearch.com: What is the background for this study? What are the main findings?

Dr. Longtin: Clostridium difficile is a major cause of infection in hospitalized patients. Current infection control measures to prevent the spread of C. difficile in hospitals focuses almost entirely on patients who present symptoms. Patients with symptoms of diarrhea due to C difficile are placed under isolation in hospitals (for example, healthcare workers will wear a gown and gloves when caring for them). However, many studies have shown that some patients may be asymptomatic carriers of C. difficile. These patients carry the C difficile bacteria in their digestive tract without being sick. It was known that these asymptomatic carriers could spread the bacteria to other patients, but it was unclear whether putting them into isolation would help prevent the spread of the microbe in hospitals. Our study tested the hypothesis that placing asymptomatic carriers under isolation could lead to a decrease in the number of infections with C  difficile.

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Study Finds No Increased Risk of Heart Failure From Incretin-Based Diabetes Drugs

MedicalResearch.com Interview with:

Kristian B. Filion, Ph.D., FAHA Assistant Professor of Medicine, Division of Clinical Epidemiology, McGill University Principal Investigator, Center for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital Associate Member, Department of Epidemiology, Biostatistics, and Occupational Health, McGill University

Dr. Kristian Filion

Kristian B. Filion, Ph.D., FAHA
Assistant Professor of Medicine, Division of Clinical Epidemiology, McGill University
Principal Investigator, Center for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital
Associate Member, Department of Epidemiology, Biostatistics, and Occupational Health, McGill University

MedicalResearch.com: What is the background for this study? What are the main findings?

Dr. Filion:  Concerns regarding the cardiovascular safety of the antidiabetic incretin-based drugs arose following the unexpected finding of an increased risk of heart failure in the SAVOR-TIMI 53 trial of the DPP-4 inhibitor saxagliptin.  Although subsequent trials did not find an increased risk of heart failure with these drugs, concerns regarding their heart failure effects remained due to the conflicting available evidence.  Furthermore, with their highly-selected patient populations, the applicability of the results of these clinical trials to patients seen in a real world setting is unclear.

We therefore examined the risk of hospitalization for heart failure associated with incretin-based drugs in patients with type 2 diabetes in a real world setting using the health records of over 1.4 million patients from six jurisdictions (four Canadian provinces, the United Kingdom, and the United States). We used a common protocol in each database and statistically combined results across databases to obtain one overall estimate.  We found that there was no evidence of an increased risk, a finding that was consistent in separate analyses for patients with and without a history of heart failure.

MedicalResearch.com: What should clinicians and patients take away from your report?

Dr. Filion:  This study provides reassurance regarding concerns about the potential risk of heart failure with the use of incretin-based drugs compared with the use of combinations of oral antidiabetic drugs such as metformin and sulfonylureas.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Dr. Filion:  It would be helpful to do additional analyses by individual incretin-based drug (i.e., by molecule), which could explain some of the heterogeneity observed in some of the clinical trials in this area.

In addition, many of the patients included in our study had a relatively short history of diabetes. In secondary analyses, we checked if the association differed by duration of treated diabetes and, although we found that it did not, it would be helpful to revisit this question in a few years as additional information becomes available.

MedicalResearch.com: Is there anything else you would like to add?

Dr. Filion:  This study was conducted by the Canadian Network for Observational Drug Effect Studies (CNODES), a pan-Canadian network funded by Health Canada and the Canadian Institutes of Health Research to study emerging drug safety issues.  CNODES has the ability to analyze a vast amount of de-identified data to efficiently respond to drug safety issues that arise after a drug is already on the market.

In this case, we were able to analyze the health records of over 1.4 million patients who were prescribed an antidiabetic medication in Canada, the United Kingdom, and the United States.

MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.

Citation:

A Multicenter Observational Study of Incretin-based Drugs and Heart Failure

Kristian B. Filion, Ph.D., Laurent Azoulay, Ph.D., Robert W. Platt, Ph.D., Matthew Dahl, B.Sc., Colin R. Dormuth, Sc.D., Kristin K. Clemens, M.D., Nianping Hu, M.D., Ph.D., J. Michael Paterson, M.Sc., Laura Targownik, M.D., M.S.H.S., Tanvir C. Turin, M.D., Ph.D., Jacob A. Udell, M.D., M.P.H., and Pierre Ernst, M.D., for the CNODES Investigators*

N Engl J Med 2016; 374:1145-1154
March 24, 2016 DOI: 10.1056/NEJMoa1506115

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

More Medical Research Interviews on MedicalResearch.com

Kristian B. Filion, Ph.D., FAHA (2016). Study Finds No Increased Risk of Heart Failure From Incretin-Based Diabetes Drugs MedicalResearch.com

Younger People May Benefit From Statins

MedicalResearch.com Interview with:

Dr George Thanassoulis MD MSc FRCPC McGill University Health Center and Research Institute Montreal, Quebec, Canada

Dr. George Thanassoulis

Dr George Thanassoulis MD MSc FRCPC
McGill University Health Center and Research Institute
Montreal, Quebec, Canada

MedicalResearch.com: What is the background for this study? What are the main findings?

Dr. Thanassoulis: Currently statins are recommended in most countries worldwide based on 10-yr risk of heart disease but because age is the best predictor of future heart disease this leads to many more older patients being eligible for statins at the expense of younger people.  This means that even young patients with higher levels of low-density cholesterol, a known cause of heart disease, are not eligible for statins until they are much older.  However, waiting for these individuals to become “old enough for treatment” permits their higher LDL  to continue to damage their arteries leading, in some cases, to advanced coronary disease at the time when statins are finally stated.  So we are missing an opportunity to effectively prevent heart disease.

What our analysis shows is that we need to consider not just someone’s risk of having a heart attack but also whether they would be expected to benefit from statins.  By integrating information from randomized trials we were able to show that there were over 9.5 million Americans who were at low risk (and not eligible for statin therapy) that would have the same absolute benefit as higher risk people who we currently treat.  These patients, as expected, were younger but had higher levels of LDL cholesterol.  We also showed that statin therapy in these individuals would avoid more than 250,000 cardiac events over 10 years. 

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Feminine Gender Characteristics Linked To Worse Cardiac Outcomes

MedicalResearch.com Interview with:

Dr. Roxanne Pelletier

Dr. Roxanne Pelletier

Roxanne Pelletier, PhD
Divisions of General Internal Medicine and of Clinical Epidemiology
Department of Medicine
The Research Institute of the McGill University Health Centre
Montreal, Quebec, Canada

Medical Research: What is the background for this study?

Dr. Pelletier: The increased risk of mortality in young females compared with males after acute coronary syndrome (ACS) remain difficult to understand. As gender-related characteristics has evolved considerably in the last decades (e.g. hours of paid work have increased significantly among women), we hypothesized that these sex differences in adverse outcomes following  acute coronary syndrome are partly explained by gender, rather than by biological sex itself.

As explained in our paper, “Gender reflects social norms and expectations ascribed to women and men, in contrast to biological characteristics that are captured by sex. Gender can be referred to as the nonbiological aspects of being male or female (e.g., social roles, personality traits).Our team had previously shown that sex differences in access to care for ACS were partly explained by these gender-related characteristics, such that both men and women presenting with acute coronary syndrome and with personality traits and social roles traditionally ascribed to women (e.g. sensitive to the needs of others, shy, household  responsibility, child care) were waiting longer before diagnostic tests and were less likely to receive invasive treatment procedures such as percutaneous coronary intervention, when compared to men and women with masculine gender-related characteristics. We then aimed to assess whether gender was also playing a role in sex differences in adverse outcomes following acute coronary syndrome.

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Who Should Have A Carotid Artery Stent vs Endarterectomy?

MedicalResearch.com Interview with:
Sophie Vincent, Medical Student
McGill University and
Kristian Filion, PhD FAHA
Assistant Professor of Medicine
Division of Clinical Epidemiology
Jewish General Hospital/McGill University

Medical Research: What is the background for this study? What are the main findings?

Response: Patients with carotid atherosclerosis causing vascular stenosis are at increased risk of stroke, which is the third leading cause of death in the United States and in Canada. Carotid artery stenting and carotid endarterectomy are the primary surgical options for the treatment of carotid stenosis. With the assumption that an endovascular approach would offer a more favorable safety profile than open surgical procedure, the use of stenting increased significantly following its entry into the market in the 1990s. However, despite this observed increase in use, the long-term safety and efficacy of stenting relative to endarterectomy remained unclear, which is why we decided to conduct this study.

Although carotid artery stenting has more favorable periprocedural outcomes with respect to myocardial infarction, hematoma, and cranial nerve palsy, the observed increased risk of stroke throughout follow-up with stenting suggests that endarterectomy remains the treatment of choice for the management of carotid stenosis.
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Off Label Prescriptions Risk More Adverse Drug Effects

MedicalResearch.com Interview with:
Tewodros Eguale, MD, PhD
Department of Epidemiology, Biostatistics, and Occupational Health,
McGill University, Montreal, Quebec, Canada
Research Fellow in Medicine
Brigham and Women’s Hospital

Medical Research: What is the background for this study?

Dr. EgualeOff-label prescribing is common and has been identified as a potentially important contributor to preventable adverse drug events (ADE). Significant deleterious effects were reported with off-label use of some drugs. Moreover, studies in children, where drugs are often used without sufficient scientific investigation, have shown that off-label uses increase the risk of ADE.  In adults, there has been no systematic investigation of the effects of off-label use in real world situation. The lack of knowledge is related to the methodological challenges of measuring off-label use and its effects; specifically the lack of link between prescribed drugs and their indication for use. The Medical Office of the XXI Century (MOXXI) electronic health record (EHR), developed by team of researchers at McGill University, facilitates the documentation of treatment indications, reasons for discontinuation of drug orders and adverse drug event. These new features provided the first opportunity to systematically monitor and evaluate off-label use and the occurrence of adverse drug events.  This study took advantage of the use of this new generation of software in a network of primary care practices to systematicaly evaluate the effect of off-label use on ADEs.

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Poor Lifestyle Linked to Acute Coronary Syndrome, Even After Event

MedicalResearch.com Interview with:
Sylvie S.L. Leung Yinko, MSc, RD

Division of Clinical Epidemiology
Research Institute of McGill University Health Centre (RI MUHC)
Montreal (QC) and
Louise Pilote, MD, MPH, PhD
Professor of Medicine McGill University and
Director of the Division of General Internal Medicine
McGill University Health Centre

Medical Research: What is the background for this study? What are the main findings?

Response: Patients with premature acute coronary syndrome (ACS) are a vulnerable population of young or middle-aged adults at risk for future cardiovascular events. However, while health behaviors such as diet, physical activity, smoking, alcohol consumption and recreational drug use are important lifestyle factors that can influence cardiovascular risk, there is limited information about health behaviors in this population group. Additionally, there is indication in the literature regarding sex and age differences in health behaviors, but whether such differences exist in patients with premature acute coronary syndrome remained to be explored.

Using data from GENESIS-PRAXY (GENdEr and Sex determInantS of Cardiovascular Disease from bench to beyond in PRemature Acute Coronary Syndrome), a large-scale prospective cohort study across Canada, US and Switzerland, we explored the health behavior profile of patients with premature ACS. As well, we examined whether there is a change in health behaviors 1 year post-ACS and assessed sex differences.

Our results showed that the health behavior profile of men and women with premature Acute Coronary Syndrome are worse than that of the general population. We found a high prevalence of poor health behaviors in a young population with only modest changes after Acute Coronary Syndrome. Health behaviors remained suboptimal and worse than the general population, especially with regards to diet, smoking and recreational drug use. Sex differences existed in the prevalence of these behaviors at baseline and 1 year post-ACS but not in the magnitude of change after the ACS event.

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Risky Decision Making May Run in Families Prone To Suicide

Fabrice Jollant, MD, PhD McGill University, Department of Psychiatry & Douglas Mental Health University Institute McGill Group for Suicide Studies Montréal (Québec), CanadaMedicalResearch.com Interview with:
Fabrice Jollant, MD, PhD
McGill University, Department of Psychiatry
& Douglas Mental Health University Institute
McGill Group for Suicide Studies
Montréal (Québec), Canada

Medical Research: What is the background for this study? What are the main findings?

Dr. Jollant: Suicide takes almost 1 million lives each year worldwide. Improving suicide prevention necessitates improving our understanding of the mechanisms leading to these complex acts. We know that while many people who died from suicide had experienced negative life events (divorce, job loss, grief), most people who experience these events will not commit suicide, not even think about suicide. Similarly, while more than 90% of suicide completers had suffered a major mental disorders (mainly depression and substance abuse) and treating these mental disorders can reduce suicide rates, 90% of patients will never die from suicide. Thus, research focuses now on the specific factors that make some individuals more vulnerable. We previously found that individuals who attempted suicide are more likely to make risky choices at a gambling task than patients who went through depression but never attempted suicide. They tend to choose the options that yield more gains immediately but are long-term disadvantageous. People who choose this way are also more likely to have problems in their interpersonal relationships, a classic trigger of suicidal crisis.

Medical Research: What are the main findings?

Dr. Jollant: This study continues our previous series of investigations. Here, we assessed decision-making in close biological relatives of suicide completers. We know that suicide is heritable and can run within some families. So, we were interested in knowing if risky decision-making could be one factor transmitted within families of suicide completers. We recruited healthy individuals who had lost a close biological relative from suicide, but never attempted suicide themselves. We found that these persons also tend to choose the riskiest options. However, we could not find some other cognitive deficits previously found in suicide attempters, e.g. deficient cognitive control. These normal cognitions may therefore counterbalance their deficits in decision-making and maybe protect them against suicide.

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