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About MacSphere

MacSphere is McMaster University's Institutional Repository. MacSphere brings together the institution's scholarly works under one umbrella to preserve and provide ongoing open access to them. MacSphere works have been selected and deposited by members of the McMaster community as part of our collective committment to sharing our knowledge with the world.

MacSphere is supported and hosted by the McMaster University Libraries.

To contribute, sign on to MacSphere with your McMaster Account. If you have any questions, refer to the user guide or contact the MacSphere Support Team for assistance.

Students wishing to deposit their PhD or Masters thesis, please follow the instructions outlined by the School of Graduate Studies.

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Recent Submissions

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    Clinical Pharmacology, Therapeutics and Toxicology High Priority Topics Across Core Clerkship Rotations
    (2025-09-02) Gandhi, Bhavya; Khakban, Iliya; Bracken, Keyna; Levinson, Anthony J; Levine, Mitchell; Holbrook, Anne M; Medicine
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    Clinical Pharmacology, Therapeutics and Toxicology Objective and Resource Mapping Across Pre-Clerkship
    (2025-02-01) Gandhi, Bhavya; Khakban, Iliya; Bracken, Keyna; Levinson, Anthony J; Levine, Mitchell; Holbrook, Anne M; Medicine
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    Does Methadone Cause QT Interval Prolongation-Related Major Adverse Cardiac Events? A Systematic Review Protocol.
    (2025) Ashe, Yaseem; Holbrook, Anne
    Methadone is a long-acting synthetic opioid drug that has been used to treat opioid use disorder (OUD) for decades [1]. Previous evidence from Cochrane reviews has shown Methadone to be the gold standard for OUD management [2]. It is meant to replace ‘street opioids’ as a form of safe supply but also as a maintenance drug that can be slowly tapered over time [3]. In Canada and the United States, methadone remains one of the most commonly utilized medications for substance use disorder. Currently, more than 400,000 people in the United States access methadone maintenance therapy, a small fraction of those who would be eligible, compared to approximately 75,000 people in Canada [4,5]. The QT interval reflects electrical depolarization and repolarization of both ventricles of the heart on an electrocardiogram [6]. Methadone has been classified by CredibleMeds as a medication with a “known” risk of QT interval prolongation (QTP) [7]. Excessive prolongation of the QT interval predisposes patients to ventricular arrhythmia including torsades de pointes (TdP), and sudden cardiac death [7]. Based on FDA recommendations, we have defined QT-prolongation-related major adverse cardiac events (MACE) as all-death, non-fatal cardiac arrest, ventricular arrhythmia (ventricular tachycardia, ventricular fibrillation and TdP), syncope, or seizure [8,9]. Interruptive warnings about the QT-prolonging effect of ‘known’ QT-prolonging medications in electronic medical records and pharmacy systems are ubiquitous in most developed countries [10]. A landmark systematic review on the effect of computerized decision support including medication decision support, showed no meaningful benefit on patient outcomes [11]. Meanwhile every time a QT- prolonging medication such as methadone is prescribed or dispensed, an interruptive alert is posted to the providers about the risk of MACE. There is a very high override rate of these alerts because of lack of high-quality evidence supporting the alert and lack of incorporation of patient-specific information including the QTc [12]. Medication alerts have also been harmful in some instances, leading to inferior substitution prescribing and more broadly producing a time and decisional conflict burden for providers [10]. Our research group has been systematically reviewing the high-quality evidence on commonly used medications listed as ‘known’ QT-prolonging drugs [8,13-16]. None of these so far has demonstrated an increased risk of MACE compared to placebo. Given the expanding use of methadone in recent years in a population thought to be vulnerable to adverse health outcomes and with limited access to formal health care, the cardiac safety profile of this medication is a concern for clinicians, policymakers, and patients alike. The true incidence of QTP-related major adverse cardiac events (MACE) caused by methadone is unknown. A preliminary search was conducted in Ovid MEDLINE and Embase to identify any recent systematic reviews or studies addressing our research question. The search yielded over 1,000 records, of which only one appeared potentially comparable. However, this publication is an older narrative review on mechanisms and clinical outcomes and includes all study designs so does not answer our research question [17]. Consequently, there appears to be a notable gap in the current evidence base, supporting the need for the present systematic review to address this underexplored area.
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    Steel City: An Analysis of the 1918 Influenza Pandemic and Respiratory Health in Hamilton, Ontario
    (2025) Boorman, Charlotte
    When understanding population health, especially in the context of pandemics, considering social, environmental, and biological implications is crucial to gain holistic perspectives. Factors such as exposure rates and susceptibility, which can be influenced by one’s social and physical environment, play a key role in health and pandemic variation among populations. This research aims to understand such varying pandemic experiences across city wards regarding the 1918 influenza pandemic in Hamilton, Ontario. Through exploring the influence of air pollution on health, a continuous issue faced by the Industrial Sector, this research investigates the environments of those living in Hamilton particularly during the pandemic, and asks: were people living in the Industrial Sector more likely to die of respiratory complications during the 1918 influenza? This study was conducted through the collection and analysis of approximately 20% of death certificates from a non-pandemic (1916) and a pandemic (1918) year. Supplementary sources such as archival records and available literature were also used to examine a potential link between poor respiratory health and mortality within the Industrial Sector during the pandemic. Social influences such as socioeconomic status, housing quality, and lifestyle, along with environmental and biological aspects such as the immunological effects of prolonged exposure to particulate matter (PM), were among the main factors analysed. This research holds potential for future studies surrounding historical and contemporary health regarding Hamilton’s Industrial Sector. This study indicates patterns of mortality across the city’s wards during the early 1900s and provides insight into determinants of health as linked to social, environmental, and biological influences. Events such as the 1918 influenza help to reveal such patterns in a population, and are valuable when analysing population health.