Michael J Rieder- Doctor of Philosophy
- Professor at Western University
Michael J Rieder
- Doctor of Philosophy
- Professor at Western University
About
443
Publications
69,433
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Introduction
Our laboratory is conducting mechanistic studies of serious adverse drug reactions as well as developing novel assays for drug and food safety. We also have a long-standing research program in steroid biology and collaborate with a number of investigators conducting clinical research in paediatrics, acute care and drug and food safety.
Skills and Expertise
Current institution
Additional affiliations
July 2008 - present
Position
- Chair
Description
- The CIHR-GSK Chair in Paediatric Clinical Pharmacology is an endowed Chair supporting research into safe and effective drug therapy for children.
Publications
Publications (443)
Introduction:
Idiosyncratic adverse drug reactions (IADRs) or drug hypersensitivity reactions (DHRs) represent a major health problem because they are unpredictable and can be severe with potential life-long or even lethal consequences. Their pathophysiology is not clear but thought to be immune mediated, supported by the significant statistical a...
Vincristine-induced peripheral neuropathy is a common and highly debilitating toxicity from vincristine treatment that affects quality of life and often requires dose reduction, potentially affecting survival. Although previous studies demonstrated genetic factors are associated with vincristine neuropathy risk, the clinical relevance of most ident...
Violence, poor mental health, and harmful substance use are commonly experienced by female sex workers (FSWs) in sub-Saharan Africa, all of which are associated with increased HIV susceptibility. We aimed to investigate the associations between violence, poor mental health and harmful alcohol/substance use with hair cortisol concentration (HCC) lev...
Individuals with high environmental sensitivity have nervous systems that are disproportionately receptive to both the protective and imperilling aspects of the environment, suggesting their mental health is strongly context-dependent. However, there have been few consolidated attempts to examine putative markers of sensitivity, across different le...
Introduction:
Stress can impact mental and physical health, especially during adolescence and young adulthood, but the extent of its contribution to dental caries is poorly understood. The present study assessed the association between perceived stress, cortisol levels (in hair and saliva), and overall caries experience of adolescents and young ad...
For numerous issues of convenience and acceptability, hair hormone data have been increasingly incorporated in the field of war trauma and forced displacement, allowing retrospective examination of several biological metrics thought to covary with refugees’ mental health. As a relatively new research method, however, there remain several complexiti...
Introduction:
Delayed drug hypersensitivity reactions (DDHRs) represent a major health problem. They are unpredictable and can cause life-long disability or even death. The pathophysiology of DDHRs is complicated, multifactorial, and not well understood mainly due to the lack of validated animal models or in vitro systems. The role of the immune s...
Refugee children are often exposed to substantial trauma, placing them at increased risk for mental illness. However, this risk can be mitigated by a capacity for resilience, conferred from multiple ecological systems (e.g., family, community), including at an individual biological level. We examined the ability of hair cortisol concentrations and...
Aims
The aim of this study is to compare the Liverpool Causality Assessment Tool vs. Naranjo Scale for screening suspected adverse drug reaction (ADR) cases.
Methods
We retrospectively reviewed patient charts with a history of suspected ADR, scored using both tools, and determined how each correlates with laboratory and other investigations. A tot...
Background:
Cystic fibrosis (CF) is a genetic disease characterized by multi-system dysfunction resulting in recurrent lung infections and progressive pulmonary disease. CF patients are at a higher risk for drug hypersensitivity reactions (DHRs) compared to the general population, which has been attributed to the recurrent need for antibiotics and...
Drug hypersensitivity reactions (DHRs) are type B adverse drug reactions (ADRs) traditionally defined as unpredictable, dose independent and not related to the drug pharmacology. DHRs, also called drug allergy if the immune system involvement is confirmed, represent around one‐sixth of all ADRs and can cause major clinical problems due to their vag...
Precision Medicine is an approach to disease treatment and prevention taking into account individual genetic, environmental, therapeutic and lifestyle variability for each person. This holistic approach to therapeutics is intended to enhance drug efficacy and safety not only across healthcare systems but for individual patients. While weight and to...
Since the advent of computed tomography (CT), iodinated contract media (ICM) has become one of the most regularly administered intravenous medications in clinical settings. Although considered generally safe, ICM is one of the most common causes of adverse drug reactions in clinical practice, accounting for more than two million adverse reactions w...
Altered secretion of cortisol, the primary effector of the hypothalamus–pituitary–adrenal axis, has been proposed as a means by which traumatic experiences compromise later mental health. However, despite the popularity of cortisol as a potential biomarker for stress and adversity, findings are inconsistent, and little is known about the impact of...
Aim: Cisplatin causes acute kidney injury (AKI) in approximately one-third of patients. Serum creatinine and urinary output are poor markers of cisplatin-induced (AKI). Metabolomics was utilized to identify predictive or early diagnostic biomarkers of cisplatin-induced AKI. Methods: Thirty-one adult head and neck cancer patients receiving cisplatin...
Historically genetics has not been considered when prescribing drugs for children. However, it is clear that genetics are not only an important determinant of disease in children but also of drug response for many important drugs that are core agents used in the therapy of common problems in children. Advances in therapy and in the ethical construc...
Background: Current pharmacovigilance (PV) methods for detection of adverse drug reactions (ADRs) fail to capture rare immune-mediated drug hypersensitivity reactions (DHRs) due to their scarcity and the lack of clear diagnostic criteria. Drug-induced serum sickness-like reactions (SSLRs) are rare type of DHRs that occur in susceptible patients 1–3...
Objective To compare the Liverpool Causality Assessment Tool versus Naranjo Scale for screening suspected adverse drug reaction (ADR) cases. Methods We retrospectively reviewed patient charts with a history of suspected ADR, scored using both instruments and determined how each correlates with laboratory and other investigations. 924 charts from th...
Introduction:
Drug hypersensitivity reactions (DHRs) represent a great challenge to clinicians due to their unpredictability and severity, notably being potentially fatal. Genetic markers for DHRs have been emerging as potential valuable clinical tools for prediction and diagnosis of DHRs. Dedicated pediatric studies in this field are scarce and m...
Aims
Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare, drug‐induced severe adverse reaction that usually occurs 3–6 weeks after initial exposure to certain drugs. It affects mainly adults and children to a lesser extent. Clinical features include fever, facial oedema, generalized skin rash, lymphadenopathy, haematological abn...
Lack of guidance and regulation for authorizing medical cannabis for conditions involving the health and neurodevelopment of children is ethically problematic as it promulgates access inequities, risk-benefit inconsistencies, and inadequate consent mechanisms. In two virtual sessions using participatory action research and consensus-building method...
Pharmacogenomics (PGx) relates to the study of genetic factors determining variability in drug response. Implementing PGx testing in paediatric patients can enhance drug safety, helping to improve drug efficacy or reduce the risk of toxicity. Despite its clinical relevance, the implementation of PGx testing in paediatric practice to date has been v...
Background
Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare but serious delayed hypersensitivity reaction that can be caused by antibiotic exposure. The reaction typically develops in 2 to 6 weeks. The pathophysiology is thought to involve toxic drug metabolites acting as a hapten, triggering a systemic response. The diagnosi...
Background:
Cisplatin, a chemotherapy used to treat solid tumors, causes acute kidney injury (AKI), a known risk factor for chronic kidney disease and mortality. AKI diagnosis relies on biomarkers which are only measurable after kidney damage has occurred and functional impairment is apparent; this prevents timely AKI diagnosis and treatment. Meta...
CASE DESCRIPTION
An 11-year-old female presented to our clinic with a dermatosis localized to her head, which had been previously diagnosed as vitiligo by two different physicians. The dermatosis was characterized by a paramedial band-like hypopigmented atrophic plaque that affected the forehead and scalp and extended from the interciliary region u...
The development of specific drug therapy for children was a paradigm‐changing event that transformed paediatric medical practice. However, a series of tragedies involving drug treatment for children resulted in a gap developing between drug regulation and practice, with the majority of drugs used in child healthcare being used off‐label, rendering...
Drug use in children is–in most cases–supported by extrapolation of data generated from clinical trials in adult populations. This puts children at higher risk of developing adverse drug reactions (ADRs) due to “off-label” use of drugs and dosing issues. Major types of ADRs are drug hypersensitivity reactions, an idiosyncratic type of ADRs that are...
Background
Serum sickness-like reaction (SSLR) is an acute inflammatory condition affecting predominantly children. The pathophysiology remains unclear, but drugs are considered the main trigger.
Objective
The aim of this study was to describe the clinical and laboratory features, triggers, and treatment modalities in children diagnosed with SSLR....
Generalized bullous fixed drug eruptions (GBFDEs) are rare in the paediatric population. We present the case of a 7-year-old girl with GBFDE believed to be secondary to oral ibuprofen, who experienced rapid resolution of lesions and cessation of blistering with a 3-week course of oral cyclosporine. To the best of our knowledge, this is the first re...
Cancer is the leading cause of death in American children older than 1 year of age. Major developments in drugs such as thiopurines and optimization in clinical trial protocols for treating cancer in children have led to a remarkable improvement in survival, from approximately 30% in the 1960s to more than 80% today. Short-term and long-term advers...
While the pathophysiology of chronic disorders varies there are three basic mechanisms - inflammation, oxidative stress and endothelial dysfunction – that are common in many chronic diseases. However, the failure of these mechanisms to work synchronously can lead to morbidity complicating the course of many chronic diseases. We analyzed data of 178...
Background
While the pathophysiology of chronic disorders varies there are three basic mechanisms - inflammation, oxidative stress and endothelial dysfunction – that are common in many chronic diseases. These mechanisms, which have a dynamic structure, are key to homeostasis. However, the failure of these mechanisms to work synchronously can lead t...
Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are potentially life-threatening, immune-mediated adverse reactions characterized by widespread erythema, epidermal necrosis, and detachment of skin and mucosa. Efforts to grow and develop functional international collaborations and a multidisciplinary interactive network focusing on...
Antimicrobial sulfonamides are important medications. However, their use is associated with major immune‐mediated drug hypersensitivity reactions with a rate that ranges from 3% to 4% in the general population. The pathophysiology of sulfa‐induced drug hypersensitivity reactions is not well understood, but accumulation of reactive metabolites (sulf...
This themed issue of the American Journal of Health-System Pharmacy is focused on drug therapy for infants, children, and adolescents and the role that pharmacists can play in ensuring that therapy is both effective and safe. This is an important issue; in addition to being our future, a quarter of the U.S. population are less than 18 years of age....
Background
Since the removal of codeine from hospital formularies, clinicians have increasingly turned to oral morphine to manage acute pain in children. However, recent evidence highlights a high prevalence of adverse effects and variable efficacy. Characterization of oral morphine pharmacokinetics and pharmacogenomics is necessary to guide the sa...
Renal injury is known to be a risk of nonsteroidal anti-inflammatory drug (NSAID) therapy in adults. While this appears to be much less common in children, there are some groups of children who do appear to be at risk of renal injury associated with NSAID therapy and clinicians caring for these patients need to be cognizant of this potential risk.
Background:
Hair cortisol analysis is increasingly being appreciated and applied in both research and medicine, aiding endocrinologists with diagnosis.
Content:
We provide an overview of hair cortisol research in general and an update on methodological considerations including the incorporation of cortisol into hair, hair growth rates, and sampl...
An underappreciated problem in child health is the risk for adverse drug reactions (ADRs). While there is an impression that children are at a lower risk than adults for ADRs, in fact a number of factors germane to pediatric therapy place certain groups of children at a high risk for adverse events associated with therapy. Given the importance of d...
Adverse drug reactions (ADRs) are common and important complications of drug therapy for children. The risk for ADRs changes over childhood, as do the nature and types of ADRs. Importantly, the risk and nature of ADRs in children are markedly different from those of adults, and adult data cannot be relied on to guide safe drug therapy in children....
Drug-induced gingival enlargement (DIGE) is a fibrotic condition associated with systemic administration of the anti-epileptic drug, phenytoin. We have previously demonstrated that periostin, which is transforming growth factor-beta (TGF-β) inducible gene, is upregulated in various fibrotic conditions including gingival enlargement associated with...
Background:
Adverse drug reactions (ADRs) are a significant problem for HIV patients, with the risk of developing ADRs increasing as the infection progresses to AIDS. However, the pathophysiology underlying ADRs remains unknown. Sulphamethoxazole (SMX) via its active metabolite SMX-hydroxlyamine, when used prophylactically for pneumocystis pneumon...
Optimising the dosing of medicines for neonates and children remains a challenge. The importance of pharmacokinetic (PK) and pharmacodynamic (PD) research is recognised both in medicines regulation and paediatric clinical pharmacology, yet there remain barriers to undertaking high-quality PK and PD studies. While these studies are essential in unde...
Drug therapy for children is one of the cornerstone developments that have sharply reduced childhood mortality. Despite this, many challenges remain in ensuring that children receive safe and effective drug therapy. There are unique issues in treating children with oral medication relating to development, existing formulations and medication accept...
Background:
Oral morphine for postoperative pain after minor pediatric surgery, while increasingly popular, is not supported by evidence. We evaluated whether oral morphine was superior to ibuprofen for at-home management of children's postoperative pain.
Methods:
We conducted a randomized superiority trial comparing oral morphine (0.5 mg/kg) wi...
Adverse drug reactions (ADRs) are a common problem in children. Health-related quality of life in patients with such conditions has not been well studied. In this study we found that health-related quality of life is adversely affected in children who developed ADRs with cutaneous manifestations.
BACKGROUND: Most paediatric surgical procedures are currently performed on an outpatient basis and pain is the most common complaint of children. Oral morphine is being increasingly prescribed. However, evidence supporting its use for at home therapy post-operatively is non-existent. Given the growing fears surrounding opioids, an evaluation of ora...
Background: Children with abdominal pain in the emergency department (ED) are at particular risk of suboptimal analgesia due to fears of missing appendicitis and absent guidelines. Many still experience pain at discharge. Acetaminophen is the most commonly used analgesic and efficacy of hyoscine butylbromide (HBB) is supported by adult evidence. Ho...
Objectives:
Dexamethasone is associated with adrenal insufficiency in adults and children with chronic disease. This association has not been studied after single-dose oral dexamethasone, the standard of care for children with croup. We hypothesized that single-dose oral dexamethasone in children with croup is associated with a transient decrease...
Background
Ketamine is commonly used for procedural sedation and analgesia (PSA) in children. Evidence suggests it can be administered intranasally (IN). We sought to review the evidence for IN ketamine for PSA in children.
Methods
We performed a systematic review of randomized trials of IN ketamine in PSA that reported any sedation-related outcom...
Adverse drug reactions (ADRs) represent a major health problem worldwide with high morbidity and mortality rates. ADRs are classified into type A (augmented) and type B (bizarre) ADRs with the former group being more common and the later less common but often severe and clinically more problematic due to their unpredictable nature and occurrence at...
Admittance to medical school has traditionally been determined on the basis of students' performance on the Medical College Admission Test (MCAT) and grade point average (GPA), which assess cognitive abilities. To supplement these predictors, medical schools also consider a semi-structured interview, which assesses non-cognitive attributes. Success...
An infant boy with steroid-resistant nephrotic syndrome (idiopathic membranous glomerulonephropathy) achieved remission with ciclosporin but developed eosinophilia and high IgE levels (max 19 000 iU/mL). Conversion to tacrolimus resulted in chronic diarrhoea (eosinophilic gastroenteritis), muscle weakness, polyserositis and failure-to-thrive. In co...
An infant boy with steroid-resistant nephrotic syndrome (idiopathic membranous glomerulonephropathy) achieved remission with ciclosporin but developed eosinophilia and high IgE levels (max 19 000 iU/mL). Conversion to tacrolimus resulted in chronic diarrhoea (eosinophilic gastroenteritis), muscle weakness, polyserositis and failure-to-thrive. In co...
Introduction:
H1 antihistamines are used for the treatment of nausea and vomiting during pregnancy as well as the symptomatic relief of asthma, urticaria, allergy, and the common cold. Although they are overall felt to be safe during pregnancy, recently several studies have challenged this assumption, as millions of women are exposed to them in th...
Background
Oral morphine has been proposed as an effective and safe alternative to codeine for after‐discharge pain in children following surgery but there are few data guiding an optimum safe oral dose.
Aims
The aim of this study was to characterize the absorption pharmacokinetics of enteral morphine in order to simulate time–concentration profil...
Background
Children’s aversions to poor and mostly bitter tastes and their inability to swallow tablets and capsules are major challenges in pediatric medicine. Sodium phenylbutyrate (NaPB) is a lifesaving waste nitrogen, alternative to urea nitrogen, for individuals suffering from urea cycle disorders. A major issue in the use of NaPB is its highl...
Oral morphine has been proposed as an effective and safer alternative to codeine for after-discharge pain in children following surgery but there are few data guiding an optimum safe oral dose. An oral dose of morphine 100 mcg.kg-1 in children resulted in serum concentrations less than 10 mcg.L-1 Doses of 200 and 300 mcg.kg-1 achieved serum concent...
The world's 1.89 billion children (0-14) too frequently receive treatments that have not been validated through clinical pharmacology research, especially in low and middle income countries. Initial findings from an international asset map of professionals and clinician scientists available to address the needs for education, research and treatment...
Table of contents
Poster walk 11: miscellaneous drug hypersensitivity 2 (P92–P94, P96–P101)
P92 16 years of experience with proton pump inhibitors (PPIs)
Javier Dionicio Elera, Cosmin Boteanu, Maria Aranzazu Jimenez Blanco, Rosario Gonzalez-Mendiola, Irene Carrasco García, Antonio Alvarez, Jose Julio Laguna Martinez
P93 Allergy evaluation of quinol...
It has historically very difficult to conduct early Phase drug studies in children for a number of reasons related to ethics, acceptability, rarity, standardization, end points, safety, dosing and feasibility. Over the past decade there have been a number of developments including novel clinical trial design, in silico pharmacology and microdosing...
Aim:
Anthracycline-induced cardiotoxicity (ACT) occurs in 57% of treated patients and remains an important limitation of anthracycline-based chemotherapy. In various genetic association studies, potential genetic risk markers for ACT have been identified. Therefore, we developed evidence-based clinical practice recommendations for pharmacogenomic...
Periconceptional folic acid significantly reduces the risk of neural tube defects. It is difficult to achieve optimal levels of folate by diet alone, even with fortification of flour, especially because flour consumption in Canada is slightly decreasing. Intermittent concerns have been raised concerning possible deleterious effects of folate supple...
Needle fear typically begins in childhood and represents an important health-related issue across the lifespan. Individuals who are highly fearful of needles frequently avoid health care. Although guidance exists for managing needle pain and fear during procedures, the most highly fearful may refuse or abstain from such procedures. The purpose of a...
Background:
Research indicates that physicians may frequently use pharmacotherapy to treat pediatric insomnia despite minimal safety data and very limited indications. Canadian data on the subject are lacking. This study aimed to determine physicians' views on and prescribing habits for sleep-promoting over-the-counter medication (OTCM) and prescr...
Purpose:
Our working hypothesis is that single bioactive phytochemicals with antioxidant properties that are important constituents of Traditional Chinese Medicine (TCM) and their defined mixtures have potential as chemoprotective agents for chronic conditions characterized by oxidative and nitrosative stress, including Alzheimer's. Here we evalua...
Purpose:
Our working hypothesis is that bioactive phytochemicals that are important constituents of Traditional Chinese Medicine and their defined mixtures have potential as complementary therapy for chemoprotection against adverse drug reactions whose toxicity is not related to the pharmacological action of the drug but where oxidative and nitros...
