337 results on '"Michael J Rieder"'
Search Results
2. War exposure, post-traumatic stress symptoms and hair cortisol concentrations in Syrian refugee children
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Demelza Smeeth, Fiona S. McEwen, Cassandra M. Popham, Elie G. Karam, John Fayyad, Dahlia Saab, Michael J. Rieder, Abdelbaset A. Elzagallaai, Stan van Uum, and Michael Pluess
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Cellular and Molecular Neuroscience ,Psychiatry and Mental health ,Molecular Biology - Abstract
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 war-related trauma on stress physiology of children and adolescents. Here we aimed to evaluate the relationships between war exposure, current living conditions, hair cortisol concentrations (HCC) and post-traumatic stress disorder (PTSD) symptoms in a large cohort of Syrian refugee children and adolescents (6–18 years) and their caregiver. This longitudinal observational study assessed Syrian refugee children and adolescents in two waves, 1 year apart, within informal tented settlements in Lebanon. The relationships between war exposure, time since leaving Syria, PTSD symptoms and HCC were investigated using linear mixed-model regression utilising both waves of data collected (Y1: N = 1574, Y2: N = 923). Hair cortisol concentration was positively, but weakly associated with the number of war-related events experienced. This was limited to those who were at least 12 years old at the time of war exposure. Conversely, HCC decreased with time since leaving Syria. HCC was also associated with PTSD symptoms but not with the quality of their current living conditions. This study revealed that changes to hypothalamic-pituitary-adrenal axis activity may accompany both earlier war exposure and current PTSD symptoms in children and adolescents. Additionally, early adolescence may be a particularly sensitive time in terms of trauma-related changes to the hypothalamic-pituitary-adrenal axis.
- Published
- 2022
3. Removing barriers to accessing medical cannabis for paediatric patients
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Richard J Huntsman, Jesse Elliott, Evan Lewis, Charlotte Moore-Hepburn, Jane Alcorn, Holly Mansell, Juan P Appendino, Richard E Bélanger, Scott Corley, Bruce Crooks, Anne Marie M Denny, Yaron Finkelstein, Allen Finley, Ryan Fung, Andrea Gilpin, Catherine Litalien, Julia Jacobs, Timothy F Oberlander, Ashley Palm, Jacob Palm, Monika Polewicz, Declan Quinn, S Rod Rassekh, Alexander Repetski, Michael J Rieder, Amy Robson-McKay, Blair Seifert, Alan Shackelford, Hal Siden, Michael Szafron, Geert ‘t Jong, Régis Vaillancourt, and Lauren E Kelly
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Pediatrics, Perinatology and Child Health - Abstract
Medical cannabis (MC) may offer therapeutic benefits for children with complex neurological conditions and chronic diseases. In Canada, parents, and caregivers frequently report encountering barriers when accessing MC for their children. These include negative preconceived notions about risks and benefits, challenges connecting with a knowledgeable healthcare provider (HCP), the high cost of MC products, and navigating MC product shortages. In this manuscript, we explore several of these barriers and provide recommendations to decision-makers to enable a family-centered and evidence-based approach to MC medicine and research for children.
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- 2023
4. Bridging the gap between bench and clinic: the importance of understanding the mechanism of iodinated contrast media hypersensitivity
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Caitlin M Sullivan, Narinder S Paul, and Michael J Rieder
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Radiology, Nuclear Medicine and imaging ,General Medicine - Abstract
Since the advent of 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 2 million adverse reactions worldwide. Currently, there are few useful tools to diagnose patient hypersensitivity, with the major limitation being the lack of consensus regarding the mechanisms of hypersensitivity to ICM. While there is an overwhelming abundance of literature pertaining to clinical features including incidence, symptomatology, and risk, few studies have further investigated the underlying mechanisms behind their clinical observations. Of the available literature discussing pathophysiology, most primary studies were completed over 20 years ago, since which the molecular characteristics of ICM have changed. Furthermore, many reviews mentioning pathophysiology fail to adequately emphasize the clinical importance of understanding the molecular pathways involved in hypersensitivity. In this review, we aim to emphasize the clinical relevance of pathophysiology as it relates to the prediction and diagnosis of hypersensitivity reactions to ICM. To this end, we will first briefly characterize hypersensitivity reactions to ICM with respect to epidemiology and clinical presentation. We will then present the existing evidence supporting various proposed mechanisms of hypersensitivity, highlighting the gaps that remain in the mechanistic delineation of both immediate and delayed reactions. Finally, we discuss the possibility of in vitro testing as a way to predict and diagnose hypersensitivity reactions, pending a more complete elucidation of mechanisms.
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- 2023
5. Pathophysiology of Drug Hypersensitivity
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Abdelbaset A. Elzagallaai and Michael J. Rieder
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Pharmacology ,Pharmacology (medical) - Abstract
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 vague clinical presentation and irregular time course. Understanding the underlying pathophysiology of DHRs is very important for their diagnosis and management. Multiple layers of evidence exist pointing to the involvement of the immune system in DHRs. Recent data have led to a paradigm shift in our understanding of the exact pathophysiology of these reactions. Numerous hypotheses proposing explanation on how a low molecular weight drug molecule can elicit an immune reaction have been proposed. In addition to the classical 'hapten' hypothesis, the reactive metabolite hypothesis, the pharmacological interaction with the immune system (p-i) concept, the danger/injury hypothesis, and the altered peptide repertoire hypothesis have been proposed. We here introduce the inflammasome activation hypothesis and the cross-reactivity hypothesis as an additional models explaining the pathophysiology of DHRs. Available data supporting these hypotheses are briefly summarized and discussed. We also introduced the cross-reactivity model, which may provide a platform to appreciate the potential role played by other factors leading to the activation of the immune system. We believe that although the drug in question could be the trigger of the reaction, the components of the immune system mediating the reaction do not act in isolation but rather affected by the proinflammatory milieu occurring at the time of the reaction. This review attempts at summarizing the available evidence to further illustrate the pathophysiology of DHRs.
- Published
- 2022
6. Metabolomic Identification of Predictive and Early Biomarkers of Cisplatin-induced Acute Kidney Injury in Adult Head and Neck Cancer Patients
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Yong Jin Lim, Steven G. Xiu, M. Sara Kuruvilla, Eric Winquist, Stephen Welch, Morgan Black, Lauren N. Faught, Jasmine Lee, Michael J. Rieder, Tom D. Blydt‐Hansen, Michael Zappitelli, and Bradley L. Urquhart
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Pharmacology ,Pharmacology (medical) - Abstract
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 (dose ≥ 70 mg m2 -1) were recruited for metabolomics analysis. Urine and serum samples were collected prior to cisplatin (pre), 24-48 hours after cisplatin (24-48h), and 5-14 days (post) after cisplatin. Based on serum creatinine concentrations measured at the post timepoint, 11/31 patients were classified with clinical AKI. Untargeted metabolomics was performed using liquid chromatography-mass spectrometry. Results: Metabolic discrimination was observed between “AKI” patients and “no AKI” patients at all timepoints. Urinary glycine, hippuric acid sulfate, 3-hydroxydecanedioc acid, and suberate were significantly different between AKI patients and no AKI patients prior to cisplatin infusion. Urinary glycine and hippuric acid sulfate were lower (-2.22-fold and -8.85-fold), whereas 3-hydroxydecanedioc acid and suberate were higher (3.62-fold and 1.91-fold) in AKI patients relative to no AKI patients. Several urine and serum metabolites were found to be altered 24-48 hours following cisplatin infusion, particularly metabolites involved with mitochondrial energetics. Conclusion: We propose glycine, hippuric acid sulfate, 3-hydroxydecanedioc acid, and suberate as predictive biomarkers of predisposition to cisplatin-induced AKI. Metabolites indicative of mitochondrial dysfunction may serve as early markers of subclinical AKI.
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- 2022
7. Pharmacogenomics in Children
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Michael J, Rieder and Abdelbaset A, Elzagallaai
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Pharmacogenetics ,Neoplasms ,Humans ,Child - Abstract
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 construct of children's research have made pharmacogenomic assessment for children much easier to pursue. It is likely that pharmacogenomics will become part of the therapeutic decision-making process for children, notably in areas such as childhood cancer where weighing benefits and risks of therapy is crucial.
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- 2022
8. Genetic markers of drug hypersensitivity in pediatrics: current state and promise
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Abdelbaset A. Elzagallaai and Michael J. Rieder
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Drug Hypersensitivity ,Genetic Markers ,Databases, Factual ,Humans ,Pharmacology (medical) ,General Medicine ,General Pharmacology, Toxicology and Pharmaceutics ,Child ,Pediatrics - Abstract
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 many published studies lack key data in this regard.This review briefly covers the current status of the use and validation of genetic markers for drug hypersensitivity in pediatrics. Classification, epidemiology and pathophysiology of DHRs are also briefly described. We searched PubMed, Ovid Medline, Web of Science, Scopus and Google Scholar literature databases for all relevant articles published from their date of commencement to March 2022. We summarized the current existing evidence and discussed the role and potential of pharmacogenomic testing in management of DHRs in pediatrics.Several genetic markers for DHRs in children have been identified and proven to be useful tools for prediction, diagnosis, and management of these adverse reactions. However, data in pediatric populations is still limited and confined to specific drugs in specific ethnic groups. Further research is needed to identify and validate more genetic markers to help guide drug therapy in children.
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- 2022
9. Novel strategy to personalise use of ibuprofen for closure of patent ductus arteriosus in preterm neonates
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Marc Pfister, Andrew Atkinson, Michael J. Rieder, George Jacob, Samira Samiee-Zafarghandy, Tamara van Donge, Cornelis Smit, Gerhard Fusch, and John N. van den Anker
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Male ,medicine.medical_specialty ,Neonatal intensive care unit ,Population ,Administration, Oral ,Gestational Age ,Ibuprofen ,Infant, Premature, Diseases ,030226 pharmacology & pharmacy ,03 medical and health sciences ,0302 clinical medicine ,Pharmacokinetics ,Intensive Care Units, Neonatal ,030225 pediatrics ,Ductus arteriosus ,medicine ,Humans ,Infant, Very Low Birth Weight ,Prospective Studies ,Neonatology ,education ,Ductus Arteriosus, Patent ,education.field_of_study ,medicine.diagnostic_test ,business.industry ,Anti-Inflammatory Agents, Non-Steroidal ,Infant, Newborn ,Gestational age ,medicine.anatomical_structure ,Therapeutic drug monitoring ,Area Under Curve ,Anesthesia ,Pediatrics, Perinatology and Child Health ,Female ,Drug Monitoring ,business ,Infant, Premature ,medicine.drug - Abstract
ObjectiveExploration of a novel therapeutic drug monitoring (TDM) strategy to personalise use of ibuprofen for closure of patent ductus arteriosus (PDA) in preterm neonates.DesignProspective, single-centre, open-label, pharmacokinetics study in preterm neonates.SettingNeonatal intensive care unit at McMaster Children’s Hospital.PatientsNeonates with a gestational age ≤28+6 weeks treated with oral ibuprofen for closure of a PDA.MethodsPopulation pharmacokinetic parameters, concentration-time profiles and exposure metrics were obtained using pharmacometric modelling and simulation.Main outcome measureAssociation between ibuprofen plasma concentrations measured at various sampling time points on the first day of treatment and attainment of the target exposure over the first 3 days of treatment (AUC0–72h >900 mg·hour/L).ResultsTwenty-three preterm neonates (median birth weight 780 g and gestational age 25.9 weeks) were included, yielding 155 plasma ibuprofen plasma samples. Starting from 8 hours’ postdose on the first day, a strong correlation between ibuprofen concentrations and AUC0–72h was observed. At 8 hours after the first dose, an ibuprofen concentration >20.5 mg/L was associated with a 90% probability of reaching the target exposure.ConclusionWe designed a novel and practical TDM strategy and have shown that the chance of reaching the target exposure (AUC0–72h >900 mg·hour/L) can be predicted with a single sample collection on the first day of treatment. This newly acquired knowledge can be leveraged to personalise ibuprofen dosing regimens and improve the efficacy of ibuprofen use for pharmacological closure of a PDA.
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- 2021
10. Paediatric pharmacotherapy and drug regulation: Moving past the therapeutic orphan
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Charlotte Moore-Hepburn and Michael J. Rieder
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Drug ,medicine.medical_specialty ,media_common.quotation_subject ,Off-label use ,030226 pharmacology & pharmacy ,paediatrics ,pharmacotherapy ,03 medical and health sciences ,0302 clinical medicine ,Pharmacotherapy ,Health care ,medicine ,Humans ,media_common.cataloged_instance ,Pharmacology (medical) ,European Union ,030212 general & internal medicine ,European union ,Child ,Intensive care medicine ,Drug Approval ,media_common ,Pharmacology ,Government ,United States Food and Drug Administration ,business.industry ,United Kingdom ,United States ,Clinical trial ,Clinical research ,Brexit ,Drug and Narcotic Control ,drug regulation ,business - Abstract
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 children therapeutic orphans. Over the past two decades changes in drug regulation led by the US Food and Drug Administration and followed by the European Union's European Medicines Agency have led to substantial changes in how new drugs with potential use in children are studied and labelled. While these changes have substantially improved labelling for new drugs, there has been much less progress with older drugs. Although the unique challenges of conducting clinical research in children have been addressed by novel clinical trial designs, many of these innovations have not been translated into approaches accepted for the drug approval process. The regulations applying to the need for paediatric studies currently are only applicable in the United States and the European Union, and there is less impetus for paediatric labelling in other jurisdictions. This impacts on a number of issues beyond labelling, including the availability of child-friendly formulations. Finally, the impact of Brexit on paediatric drug studies in the UK remains unclear and is subject to ongoing negotiations between the UK government and the European Union.
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- 2021
11. DRESS induced by amoxicillin-clavulanate in two pediatric patients confirmed by lymphocyte toxicity assay
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Bruce Carleton, Tiffany Wong, Raymond H. Mak, Hasandeep Kular, Abdelbaset A. Elzagallaai, Michael J. Rieder, and Arun Dhir
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Drug ,lcsh:Immunologic diseases. Allergy ,Allergy ,medicine.drug_class ,media_common.quotation_subject ,Antibiotics ,“Drug reaction with eosinophilia and systemic symptoms” ,Lymphocyte Toxicity Assay ,Case Report ,030207 dermatology & venereal diseases ,03 medical and health sciences ,0302 clinical medicine ,medicine ,media_common ,030201 allergy ,business.industry ,Respiratory infection ,General Medicine ,Atopic dermatitis ,medicine.disease ,Penicillin ,Delayed hypersensitivity ,Toxicity ,Immunology ,Amoxicillin-clavulanate ,business ,DRESS ,lcsh:RC581-607 ,medicine.drug - Abstract
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 diagnosis is made clinically but can be confirmed using assays such as the lymphocyte toxicity assay (LTA), which correlates cell death upon exposure to drug metabolites with susceptibility to hypersensitivity reactions. Case presentations Case 1 involves a previously healthy 11-month-old male with first exposure to amoxicillin-clavulanate, prescribed for seven days to treat a respiratory infection. The patient developed DRESS fourteen days after starting the drug and was successfully treated with corticosteroids. LTA testing confirmed patient susceptibility to hypersensitivity reactions with amoxicillin-clavulanate. Parental samples were also tested, showing both maternal and paternal susceptibility. Neither parent reported prior hypersensitivity reactions. Lifelong penicillin avoidance for the patient was advised along with the notation in medical records of penicillin allergy. The parents were advised to avoid penicillin class antibiotics and be monitored closely for DRESS if they are exposed. Case 2 involves an 11-year-old female with atopic dermatitis with first exposure to amoxicillin-clavulanate, prescribed for ten days to treat a secondary bacterial skin infection. She developed DRESS eleven days after starting antibiotics and was successfully treated with corticosteroids. LTA testing confirmed patient susceptibility to hypersensitivity reactions with amoxicillin-clavulanate. Maternal samples were also tested and showed sensitivity. The mother reported no prior hypersensitivity reactions. Lifelong penicillin avoidance for the patient was advised along with the notation in medical records of penicillin allergy. Conclusions Amoxicillin-clavulanate is a commonly used antibiotic and the cases we have described suggest that it should be recognized as a potential cause of DRESS in pediatric patients. Furthermore, these cases contribute to current literature supporting that there may be a shorter latent period in DRESS induced by antibiotics. We have also shown that the LTA can be a helpful tool to confirm DRESS reactions, and that testing may have potential implications for family members.
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- 2021
12. The role of
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Abdelbaset A, Elzagallaai, Awatif M, Abuzgaia, Blanca R, Del Pozzo-Magaña, Eman, Loubani, and Michael J, Rieder
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- 2022
13. Drug reaction with eosinophilia and systemic symptoms (DRESS): A tertiary care centre retrospective study
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Blanca R. Del Pozzo‐Magaña, Michael J. Rieder, Facundo Garcia‐Bournissen, and Alejandro Lazo‐Langner
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Pharmacology ,Adult ,Male ,Adolescent ,Exanthema ,Middle Aged ,Tertiary Care Centers ,Young Adult ,Child, Preschool ,Drug Hypersensitivity Syndrome ,Eosinophilia ,Edema ,Humans ,Pharmacology (medical) ,Female ,Angioedema ,Child ,Aged ,Retrospective Studies - Abstract
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 abnormalities and internal organ involvement. The objective was to investigate the clinical and laboratory features of patients with DRESS in our centre.We retrospectively describe and analyse 19 cases of DRESS whose diagnosis was based on the RegiSCAR criteria (≥6 points) that occurred from January 2009 to December 2019.Patient age ranged from 4 to 76 years (4 children/15 adults); 10 were female (52.3%). The most common culprit drugs were antibiotics (74%) and anticonvulsants (21%). The most common comorbidities were epilepsy (26%) and hypertension (26%). All patients developed cutaneous manifestations and of those, 58% presented facial oedema. Liver function tests, urea/creatinine and troponin elevation were present in 74, 32 and 42%, respectively. The median time to develop the skin rash after the drug exposure was 3.7 weeks (interquartile range 2.4-4.2 wk). Eosinophilia (≥0.7 × 10DRESS is a serious condition with significant morbidity and mortality, which requires more research for a better understanding.
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- 2022
14. Les opioïdes par voie orale en remplacement de la codéine pour contrôler la douleur chez les enfants
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Geert W. ‘t Jong and Michael J. Rieder
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Gynecology ,03 medical and health sciences ,medicine.medical_specialty ,0302 clinical medicine ,030202 anesthesiology ,business.industry ,Pediatrics, Perinatology and Child Health ,Position Statement / Document de Principes ,medicine ,business ,030226 pharmacology & pharmacy - Abstract
Résumé La douleur est un problème courant chez les enfants. Des mesures pharmacologiques et non pharmacologiques sont utilisées pour la prendre en charge. Depuis quelques décennies, les opioïdes par voie orale sont populaires pour soulager la douleur modérée à grave. La codéine a longtemps été l’opioïde par voie orale le plus connu pour les enfants. Pour des raisons de sécurité, elle est désormais nettement moins accessible et moins employée. Divers autres opioïdes la remplacent, mais les données sur leur efficacité et leur sécurité sont limitées chez les enfants. L’oxycodone par voie orale emprunte les mêmes voies métaboliques que la codéine, mais sa pharmacocinétique est très variable. Les données sur la sécurité et l’efficacité de l’hydromorphone et du tramadol par voie orale chez les enfants sont également limitées. Lorsqu’on y recourt au lieu de la codéine, la morphine par voie orale est l’opiacé dont la sécurité et l’efficacité sont les mieux démontrées chez les enfants. Des recherches devront être réalisées pour explorer d’autres approches relatives aux médicaments opioïdes et non opioïdes, afin d’orienter les traitements analgésiques fondés sur des données probantes qui soulageront la douleur modérée à grave chez les enfants.
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- 2021
15. The use of oral opioids to control children’s pain in the post-codeine era
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Michael J Rieder and Geert 't Jong
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medicine.medical_specialty ,Morphine ,business.industry ,Codeine ,Hydromorphone ,030226 pharmacology & pharmacy ,03 medical and health sciences ,0302 clinical medicine ,Analgesic therapy ,Opioid ,030225 pediatrics ,Pediatrics, Perinatology and Child Health ,Position Statement / Document de Principes ,medicine ,Tramadol ,Opiate ,Intensive care medicine ,business ,Oxycodone ,medicine.drug - Abstract
Pain is a common problem for children, and pain management comprises both pharmacologic and nonpharmacologic measures. For moderate to severe pain, oral opioids have been a popular choice for the last few decades. Codeine has historically been the best-known oral opioid for use in children. However, availability and use of codeine have sharply declined due to safety concerns. A variety of other opioids have been used in place of codeine, but data are limited regarding their efficacy and safety in children. While the same pathways metabolize oral oxycodone as codeine, oxycodone’s pharmacokinetics varies widely. There are also limited data on the safety and efficacy of oral hydromorphone and tramadol use for children. Oral morphine is the opiate alternative to codeine for which there is the most evidence of safety and efficacy in children. Research is needed to investigate both other opioids and non-opioid approaches to guide evidence-based analgesic therapy and treatment for moderate-to-severe pain in children.
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- 2021
16. Severe Generalized Bullous Fixed Drug Eruption Treated with Cyclosporine: A Case Report and Literature Review
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Erin R. Peebles, Hailey C. Barootes, Javed Mohammed, Michael J. Rieder, Doreen Matsui, and Awatif M. Abuzgaia
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medicine.medical_specialty ,Dermatology ,systemic therapy ,030207 dermatology & venereal diseases ,03 medical and health sciences ,0302 clinical medicine ,Case and Review ,medicine ,lcsh:Dermatology ,Fixed drug eruptions ,Drug reaction ,Pharmacology ,Systemic therapy ,business.industry ,lcsh:RL1-803 ,Ibuprofen ,medicine.disease ,Drug eruption ,drug reaction ,030220 oncology & carcinogenesis ,pharmacology ,business ,medicine.drug ,Paediatric population - Abstract
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 report of a paediatric case of GBFDE treated with cyclosporine. In our report, we review published cases of GBFDE in children, and all adult cases managed with cyclosporine.
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- 2021
17. Améliorer la réglementation du cannabis médical au Canada pour mieux servir les patients pédiatriques
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Richard J. Huntsman, Lauren E. Kelly, Jane Alcorn, Juan Pablo Appendino, Richard E. Bélanger, Bruce Crooks, Yaron Finkelstein, Andrea Gilpin, Evan Lewis, Catherine Litalien, Julia Jacobs, Charlotte Moore-Hepburn, Timothy Oberlander, S. Rod Rassekh, Alexander E. Repetski, Michael J. Rieder, Alan Shackelford, Hal Siden, Michael Szafron, Geert W. ‘t Jong, and Régis Vaillancourt
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Commentaire ,General Medicine - Published
- 2021
18. Not every white spot is vitiligo
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Blanca R Del Pozzo-Magaña and Michael J Rieder
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medicine.medical_specialty ,White (horse) ,business.industry ,A Picture Says a Thousand Words ,Pediatrics, Perinatology and Child Health ,medicine ,Vitiligo ,medicine.disease ,business ,Dermatology - Published
- 2021
19. War exposure, post-traumatic stress symptoms and hair cortisol concentrations in Syrian refugee children
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Demelza, Smeeth, Fiona S, McEwen, Cassandra M, Popham, Elie G, Karam, John, Fayyad, Dahlia, Saab, Michael J, Rieder, Abdelbaset A, Elzagallaai, Stan, van Uum, and Michael, Pluess
- Abstract
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 war-related trauma on stress physiology of children and adolescents. Here we aimed to evaluate the relationships between war exposure, current living conditions, hair cortisol concentrations (HCC) and post-traumatic stress disorder (PTSD) symptoms in a large cohort of Syrian refugee children and adolescents (6-18 years) and their caregiver. This longitudinal observational study assessed Syrian refugee children and adolescents in two waves, 1 year apart, within informal tented settlements in Lebanon. The relationships between war exposure, time since leaving Syria, PTSD symptoms and HCC were investigated using linear mixed-model regression utilising both waves of data collected (Y1: N = 1574, Y2: N = 923). Hair cortisol concentration was positively, but weakly associated with the number of war-related events experienced. This was limited to those who were at least 12 years old at the time of war exposure. Conversely, HCC decreased with time since leaving Syria. HCC was also associated with PTSD symptoms but not with the quality of their current living conditions. This study revealed that changes to hypothalamic-pituitary-adrenal axis activity may accompany both earlier war exposure and current PTSD symptoms in children and adolescents. Additionally, early adolescence may be a particularly sensitive time in terms of trauma-related changes to the hypothalamic-pituitary-adrenal axis.
- Published
- 2022
20. Pharmacogenomic testing in paediatrics: clinical implementation strategies
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Charlotte I. S. Barker, Gabriella Groeneweg, Anke H. Maitland‐van der Zee, Michael J. Rieder, Daniel B. Hawcutt, Tim J. Hubbard, Jesse J. Swen, and Bruce C. Carleton
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Pharmacology ,children ,Cost-Benefit Analysis ,precision medicine ,personalised medicine ,Humans ,Pharmacology (medical) ,Child ,Pediatrics ,Netherlands ,Pharmacogenomic Testing ,pharmacogenetics - Abstract
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 variable and limited. As with most paediatric pharmacological studies, there are well-recognised barriers to obtaining high-quality PGx evidence, particularly when patient numbers may be small, and off-label or unlicensed prescribing remains widespread. Furthermore, trials enrolling small numbers of children can rarely, in isolation, provide sufficient PGx evidence to change clinical practice, so extrapolation from larger PGx studies in adult patients, where scientifically sound, is essential. This review paper discusses the relevance of PGx to paediatrics and considers implementation strategies from a child health perspective. Examples are provided from Canada, the Netherlands and the UK, with consideration of the different healthcare systems and their distinct approaches to implementation, followed by future recommendations based on these cumulative experiences. Improving the evidence base demonstrating the clinical utility and cost-effectiveness of paediatric PGx testing will be critical to drive implementation forwards. International, interdisciplinary collaborations will enhance paediatric data collation, interpretation and evidence curation, while also supporting dedicated paediatric PGx educational initiatives. PGx consortia and paediatric clinical research networks will continue to play a central role in the streamlined development of effective PGx implementation strategies to help optimise paediatric pharmacotherapy.
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- 2022
21. Pharmacogenomics in Children
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Michael J. Rieder and Abdelbaset A. Elzagallaai
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- 2022
22. Paediatric serum sickness-like reaction: A 10-year retrospective cohort study
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Barbara Murray, Alejandro Lazo-Langner, Michael J Rieder, Blanca R Del Pozzo-Magaña, and Awatif Abuzgaia
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Drug ,medicine.medical_specialty ,Erythema ,media_common.quotation_subject ,Adverse drug reaction ,Pediatrics ,03 medical and health sciences ,Serum Sickness-like Reaction ,0302 clinical medicine ,030225 pediatrics ,Internal medicine ,medicine ,Children ,media_common ,030203 arthritis & rheumatology ,business.industry ,Retrospective cohort study ,Original Articles ,Amoxicillin ,medicine.disease ,Rash ,Pathophysiology ,Pediatrics, Perinatology and Child Health ,Toxicity ,medicine.symptom ,business ,medicine.drug - Abstract
BackgroundSerum sickness-like reaction (SSLR) is an acute inflammatory condition affecting predominantly children. The pathophysiology remains unclear, but drugs are considered the main trigger.ObjectiveThe aim of this study was to describe the clinical and laboratory features, triggers, and treatment modalities in children diagnosed with SSLR.MethodsWe conducted a 10-year retrospective cohort study including all paediatric patients (0 to 18 years old) with query SSLR referred to the Adverse Drug Reactions Clinic at the Children’s Hospital of Western Ontario. Diagnostic criteria included acute skin rash plus joint inflammation with or without fever.ResultsWe included 83 patients (47 females). Age ranged from 11 months to 12 years (mean 3.2 years). Amoxicillin was the trigger in 82.7% of patients. The mean time between the exposure to the triggering drug and the development of the symptoms was 8.5 days. Urticaria-like and Erythema multiforme-like lesions were present in 35% and 38.5% of the cases, respectively. Joint inflammation affecting hands/feet was present in 60%. Pruritus, lip/eye swelling, and fever were reported in 33, 31, and 45% of patients, respectively. The lymphocyte toxicity assay (LTA) showed incremental T-cell toxicity in 32 of 34 patients. Children that received treatment with antihistamines/nonsteroidal anti-inflammatory drugs (NSAIDs) plus oral steroids had a mean recovery time shorter than those treated only with antihistamines/NSAIDs (6 versus 8 days; P=0.09).ConclusionsIn our study, SSLR was mostly triggered by amoxicillin and had a mean time presentation of 8.5 days. Further prospective and well-conducted studies are needed.
- Published
- 2021
23. 95 Baseline body-mass-index and risk for obesity in children with rheumatic disease starting high-dose prednisone therapy
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Michael J. Miller, Roberta A. Berard, Michael J. Rieder, Renee Pang, and Erkan Demirkaya
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Pediatrics ,medicine.medical_specialty ,business.industry ,Rheumatic disease ,medicine.disease ,Obesity ,Prednisone ,Pediatrics, Perinatology and Child Health ,medicine ,Abstract / Résumés ,business ,Baseline (configuration management) ,Body mass index ,medicine.drug - Abstract
Primary Subject area Rheumatology Background Prednisone is a glucocorticoid (GC) medication commonly used in moderate (>7.5 mg/day) to high doses (≥ 1 mg/kg/day to maximum 60 mg/day) for children with moderate to severe presentations of rheumatic disease, including systemic lupus erythematosus (SLE), juvenile idiopathic arthritis (JIA), and juvenile dermatomyositis (JDM). Adverse effects (AE) to GCs impose a significant burden on health and quality of life including frequent development of weight gain, mood changes, sleep difficulties, osteoporosis, and Cushingoid features, amongst others. Objectives We sought to evaluate a possible relationship between baseline patient body-mass-index (BMI) measure and development of select GC-mediated toxicity within the first 12 months of starting moderate or high-dose prednisone therapy using conventional weight-based dosing of prednisone. Secondary outcomes were to examine rates of GC-mediated hypertension, osteopenia, and osteoporosis. Design/Methods We performed a retrospective chart review on children with rheumatic disease aged ≤ 17 years treated with moderate and high-dose prednisone therapy at a single Canadian academic hospital between January 1, 2010 and December 31, 2019. Demographic variables collected included diagnosis, age, sex, ethnicity. Clinical variables collected include weight, height, and body-mass-index (BMI), hepatitis (AST>41 U/L, ALT>40 U/L, or GGT>60 U/L), proteinuria (>0.1 g/L), and presence of hypoalbuminemia ( Baseline characteristics, which were significant for the subsequent development of obesity during the first 12 months at the bivariate level (p < 0 .05), were included as predictors of obesity in separate logistic regression analyses. In each regression analysis, we also adjusted for baseline BMI, and for confounding variables of hepatitis, hypoalbuminemia (albumin less than 38 grams per litre), proteinuria and prednisone dose. We conducted a complete case analysis, and all analyses were performed using SPSS v.26 (IBM Corp., Armonk, NY, USA), and p-values < 0 .05 were considered statistically significant. Results Seventy-four charts were reviewed, and 72 patients met criteria for analysis. The median prednisone dose was 35 mg per day (IQR 20 to 60 mg), and median duration of therapy was 302 days (IQR 126.75 to 581.25). Thirty-five (48.6%) patients developed obesity, 33 (45.8%) hypertension, five (7.0%) osteopenia, and three (4.2%) osteoporosis. Greater BMI at baseline was associated with greater total weight gain (OR 4.04, 95% CI = [1.98-8.33], p < 0 .001). Conclusion Greater baseline patient BMI may be a predictor of weight gain on high-dose prednisone therapy in children with rheumatic disease requiring high-dose therapy. Further work is required to determine methods for individualized prednisone dosing and counseling and behavioral interventions to mitigate risk for weight gain.
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- 2021
24. Improving the regulation of medical cannabis in Canada to better serve pediatric patients
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Michael J. Rieder, Lauren E. Kelly, Geert W. ‘t Jong, Bruce Crooks, Richard E. Bélanger, Régis Vaillancourt, Timothy Oberlander, Michael Szafron, Jane Alcorn, Julia Jacobs, S. Rod Rassekh, Evan J. H. Lewis, Charlotte Moore-Hepburn, Catherine Litalien, Alexander E. Repetski, Andrea Gilpin, Richard J. Huntsman, Hal Siden, Alan E. Shackelford, Yaron Finkelstein, and Juan Pablo Appendino
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Canada ,medicine.medical_specialty ,biology ,Cannabinoids ,business.industry ,Health Policy ,Conventional treatment ,MEDLINE ,Medical Marijuana ,General Medicine ,biology.organism_classification ,Practice Guidelines as Topic ,Medical cannabis ,Commentary ,Government Regulation ,medicine ,Humans ,Cannabis ,Child ,Intensive care medicine ,business ,Adverse effect - Abstract
Key points Children with chronic debilitating illness and pain are increasingly using cannabis for medical purposes, particularly when conventional treatment options have limited benefit or substantial adverse effects. Caregivers are becoming aware of evidence that suggests medical cannabis provides
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- 2021
25. L’amélioration des médicaments à usage pédiatrique : une prescription pour les enfants et les adolescents canadiens
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Andrea Gilpin, Charlotte Moore Hepburn, Michael J. Rieder, Barry Power, Thierry Lacaze-Masmonteil, Stuart M. MacLeod, Maury Pinsk, Yaron Finkelstein, Shinya Ito, Geert’t Jong, Steven P. Miller, L. Lee Dupuis, Emily Gruenwoldt, Julie Autmizguine, Avrum Denburg, Catherine Litalien, Martin Offringa, and Deborah M. Levy
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business.industry ,Pediatrics, Perinatology and Child Health ,Medicine ,business ,Position Statements / Documents de Principes - Published
- 2019
26. Corrigendum to ‘SJS/TEN 2019: From science to translation’ [J. Dermatol. Sci. 98/1 (2020) 2–12]
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Sonia Whyte-Croasdaile, Ricardo Cibotti, Alfonso Iovieno, Cristina Olteanu, Jessica Weintraub, Bruce Carleton, Mayumi Ueta, Jonathan Peter, Mahyar Etminan, Jean McCawley, Cynthia Sung, Wan-Chun Chang, Sherrie J. Divito, Maja Mockenhaupt, Julienne Jagdeo, Rannakoe J. Lehloenya, Simona Volpi, Hyon K. Choi, Neil H. Shear, Lisa M. Wheatley, Hajirah N. Saeed, Hongsheng Wang, Michael R. Ardern-Jones, Robyn Lim, Christine Shieh, Diane Forbes, Charles S. Bouchard, Agnieszka K. Biala, Elizabeth J. Phillips, Robert G. Micheletti, Zhao-Qing Wang, Shuen-Iu Hung, Wen-Hung Chung, Chia Ling Hsieh, Karen Dewar, Sophie Le Pallec, Nicole Chapman, Jason A Trubiano, Michael J. Rieder, James H. Holmes, Ulrike Dehaeck, Wanpen Anderson, Chen Wan, Mee Kum Kim, Galen E.B. Wright, Munir Pirmohamed, Angie Lowe, Teresa Bellón, Sonia N. Yeung, Katie Niemeyer, Julie McCawley, Sheng-Ying Tsou, Gianpiero L. Cavalleri, Sabine Straus, Elyse A. Hope, Chonlaphat Sukasem, Thomas M. Beachkofsky, Li Zhou, Michael A. Norcross, Cindy Whale, Paul Anderson, Jennifer L. Goldman, Mario E. Lacouture, Esther Fuchs, Douglas Oboh, Riichiro Abe, Kristina B. Williams, James Chodosh, David M. Koelle, and Helena B. Pasieka
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Published Erratum ,Political science ,MEDLINE ,media_common.cataloged_instance ,Library science ,Regret ,Dermatology ,European union ,Molecular Biology ,Biochemistry ,media_common - Abstract
The authors regret not all contributing authors correctly acknowledged funding. Jonathan Peter’s IMARI-Africa project (AFRISCAR) is part of the EDCTP2 programme supported by the European Union (grant number TMA2017SF-1981 ). The authors would like to apologise for any inconvenience caused.
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- 2021
27. A machine learning based exploration of COVID-19 mortality risk
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Amirata Ghorbani, Reza Lashgari, Zsolt Jobbagy, Safieddin Safavi-Naeini, Arda Kiani, Ehsan Kamrani, Mahdi Mahdavi, Atefeh Abedini, Vida Khanlarzadeh, Hadi Choubdar, Michael J. Rieder, and Erfan Zabeh
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0301 basic medicine ,Male ,Viral Diseases ,Support Vector Machine ,Computer science ,Epidemiology ,Health Care Providers ,Comorbidity ,computer.software_genre ,Biochemistry ,Severity of Illness Index ,Machine Learning ,0302 clinical medicine ,Medical Conditions ,Feature (machine learning) ,Medicine and Health Sciences ,Electronic Health Records ,Medical Personnel ,Radiation treatment planning ,Wearable technology ,Virus Testing ,Aged, 80 and over ,Multidisciplinary ,Mortality rate ,Middle Aged ,Professions ,Infectious Diseases ,Medicine ,Female ,Symptom Assessment ,Research Article ,Adult ,Risk ,Computer and Information Sciences ,Death Rates ,Science ,MEDLINE ,Machine learning ,03 medical and health sciences ,Young Adult ,Population Metrics ,Artificial Intelligence ,Diagnostic Medicine ,Support Vector Machines ,Physicians ,Humans ,Pandemics ,Aged ,Population Biology ,business.industry ,SARS-CoV-2 ,Biology and Life Sciences ,COVID-19 ,Covid 19 ,Models, Theoretical ,Triage ,Support vector machine ,Health Care ,030104 developmental biology ,People and Places ,Resource allocation ,Population Groupings ,Artificial intelligence ,business ,computer ,030217 neurology & neurosurgery ,Biomarkers ,Forecasting - Abstract
Early prediction of patient mortality risks during a pandemic can decrease mortality by assuring efficient resource allocation and treatment planning. This study aimed to develop and compare prognosis prediction machine learning models based on invasive laboratory and noninvasive clinical and demographic data from patients’ day of admission. Three Support Vector Machine (SVM) models were developed and compared using invasive, non-invasive, and both groups. The results suggested that non-invasive features could provide mortality predictions that are similar to the invasive and roughly on par with the joint model. Feature inspection results from SVM-RFE and sparsity analysis displayed that, compared with the invasive model, the non-invasive model can provide better performances with a fewer number of features, pointing to the presence of high predictive information contents in several non-invasive features, including SPO2, age, and cardiovascular disorders. Furthermore, while the invasive model was able to provide better mortality predictions for the imminent future, non-invasive features displayed better performance for more distant expiration intervals. Early mortality prediction using non-invasive models can give us insights as to where and with whom to intervene. Combined with novel technologies, such as wireless wearable devices, these models can create powerful frameworks for various medical assignments and patient triage.
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- 2021
28. A Canadian Study of Cisplatin Metabolomics and Nephrotoxicity (ACCENT): A Clinical Research Protocol
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Natasha A. Jawa, Michael Brudno, Paul C. Boutros, Alexandra P. Zorzi, Bradley L. Urquhart, Shahrad Rod Rassekh, Eric Winquist, Ryan Huang, Geoffrey Liu, Cheryl Ho, Geoffrey D.E. Cuvelier, Bruce Carleton, Stephen Welch, David S. Wishart, Sushrut S. Waikar, Yong Jin Lim, Tom Blydt-Hansen, Mike Guron, Lakshman Gunaratnam, Michael Zappitelli, Giles Lajoie, Paul C. Nathan, Sharon Abish, Michael J. Rieder, Anshika Jain, Jasmine Lee, Sara Kuruvilla, Matthew A. Weir, and Khosrow Adeli
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Oncology ,medicine.medical_specialty ,Kidney Disease ,pediatrics ,medicine.medical_treatment ,Renal and urogenital ,Nephrotoxicity ,03 medical and health sciences ,0302 clinical medicine ,Clinical Research ,Internal medicine ,medicine ,cohort study ,Risk factor ,030304 developmental biology ,Cancer ,Cisplatin ,0303 health sciences ,Chemotherapy ,screening and diagnosis ,business.industry ,Prevention ,Acute kidney injury ,cisplatin nephrotoxicity ,medicine.disease ,metabolomics ,Diseases of the genitourinary system. Urology ,3. Good health ,Clinical Research Protocol ,Detection ,Clinical research ,acute kidney injury ,Nephrology ,030220 oncology & carcinogenesis ,RC870-923 ,business ,Kidney disease ,Cohort study ,medicine.drug ,4.2 Evaluation of markers and technologies - Abstract
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. Metabolomics seeks to identify metabolite patterns involved in cell tissue metabolism related to disease or patient factors. The A Canadian study of Cisplatin mEtabolomics and NephroToxicity (ACCENT) team was established to harness the power of metabolomics to identify novel biomarkers that predict risk and discriminate for presence of cisplatin nephrotoxicity, so that early intervention strategies to mitigate onset and severity of AKI can be implemented.Describe the design and methods of the ACCENT study which aims to identify and validate metabolomic profiles in urine and serum associated with risk for cisplatin-mediated nephrotoxicity in children and adults.Observational prospective cohort study.Six Canadian oncology centers (3 pediatric, 1 adult and 2 both).Three hundred adults and 300 children planned to receive cisplatin therapy.During two cisplatin infusion cycles, serum and urine will be measured for creatinine and electrolytes to ascertain AKI. Many patient and disease variables will be collected prospectively at baseline and throughout therapy. Metabolomic analyses of serum and urine will be done using mass spectrometry. An untargeted metabolomics approach will be used to analyze serum and urine samples before and after cisplatin infusions to identify candidate biomarkers of cisplatin AKI. Candidate metabolites will be validated using an independent cohort.Patients will be recruited before their first cycle of cisplatin. Blood and urine will be collected at specified time points before and after cisplatin during the first infusion and an infusion later during cancer treatment. The primary outcome is AKI, defined using a traditional serum creatinine-based definition and an electrolyte abnormality-based definition. Chart review 3 months after cisplatin therapy end will be conducted to document kidney health and survival.It may not be possible to adjust for all measured and unmeasured confounders when evaluating prediction of AKI using metabolite profiles. Collection of data across multiple sites will be a challenge.ACCENT is the largest study of children and adults treated with cisplatin and aims to reimagine the current model for AKI diagnoses using metabolomics. The identification of biomarkers predicting and detecting AKI in children and adults treated with cisplatin can greatly inform future clinical investigations and practices.Le cisplatine, un agent utilisé en chimiothérapie pour traiter les tumeurs solides, entraîne de l’insuffisance rénale aiguë (IRA); un facteur de risque connu de néphropathie chronique et de mortalité. Le diagnostic de l’IRA repose sur des biomarqueurs qui ne sont mesurables qu’après l’apparition d’une lésion rénale et d’une déficience fonctionnelle; ce qui empêche le diagnostic et le traitement précoce de la maladie. La métabolomique s’efforce d’établir le profil des métabolites impliqués dans le métabolisme des tissus cellulaires en relation avec des facteurs liés à la maladie ou au patient. Une étude canadienne portant sur la métabolomique et la néphrotoxicité du cisplatine (ACCENT) s’est amorcée, elle explore la puissance de la métabolomique dans l’identification de nouveaux biomarqueurs permettant de prédire le risque de néphrotoxicité du cisplatine et d’en distinguer la présence. L’objectif étant de mettre en œuvre des stratégies d’intervention précoce, dès l’apparition de l’IRA, et de limiter la gravité de la maladie.Décrire la conception et la méthodologie de l’étude ACCENT. Cette étude vise à établir et à valider des profils métabolomiques, dans l’urine et le sérum, associés au risque de néphrotoxicité médiée par le cisplatine chez les enfants et les adultes.Étude de cohorte prospective.Six centres canadiens d’oncologie (trois centres pédiatriques, un centre pour adultes et deux centres mixtes).L’étude porte sur 300 adultes et 300 enfants pour qui un traitement par cisplatine est prévu.L’IRA sera confirmée par mesure de la créatinine et des électrolytes dans le sérum et l’urine au cours de deux cycles de perfusion de cisplatine. De nombreuses variables relatives au patient et à la maladie seront recueillies prospectivement avant et pendant le traitement. Les analyses métabolomiques des échantillons de sérum et d’urine seront effectuées par spectrométrie de masse. Une approche métabolomique non ciblée sera utilisée pour analyser les échantillons avant et après les perfusions de cisplatine pour identifier les biomarqueurs candidats d’une IRA découlant du traitement par cisplatine. Les métabolites candidats seront validés dans une cohorte indépendante.Les patients seront recrutés avant le premier cycle de cisplatine. Le sang et l’urine seront recueillis à des moments précis, soit avant et pendant le traitement; plus précisément lors de la première perfusion, puis d’une perfusion subséquente au cours du traitement contre le cancer. Le principal critère d’évaluation est la présence d’IRA, laquelle sera établie selon la définition classique fondée sur la mesure de la créatinine sérique et d’une autre définition fondée sur les anomalies électrolytiques. Un examen des dossiers trois mois après la fin du traitement par cisplatine sera effectué afin de documenter la santé rénale et la survie des patients.Il pourrait être impossible de corriger tous les facteurs confusionnels mesurés et non mesurés lors de l’évaluation de la prédiction de l’IRA à l’aide de profils de métabolites. La collecte de données sur plusieurs sites sera un défi.ACCENT est la plus vaste étude portant sur des enfants et des adultes traités avec le cisplatine; cette étude tente de revoir le modèle actuel en utilisant la métabolomique pour diagnostiquer l’IRA. L’identification de biomarqueurs permettant de prédire et de détecter l’IRA chez les enfants et les adultes traités par cisplatine pourrait grandement éclairer les futures études et pratiques cliniques.ClinicalTrials.gov, insuffisance rénale induite par le cisplatine, NCT04442516.
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- 2021
29. Comparison of Regularly Scheduled Ibuprofen Versus 'Pro Re Nata' for Ankle Sprains in Children Treated in the Emergency Department: A Randomized Controlled Trial
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Katelyn M Bartlett, Rodrick Lim, Michael J. Rieder, Gurinder Sangha, Jamie A. Seabrook, and Natasha Lepore
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medicine.medical_specialty ,Adolescent ,Visual analogue scale ,Ibuprofen ,accident and emergency ,Pediatrics ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Double-Blind Method ,Randomized controlled trial ,law ,Pro re nata ,030225 pediatrics ,Internal medicine ,Outcome Assessment, Health Care ,ankle ,Humans ,Medicine ,Ankle Injuries ,Child ,Adverse effect ,Pain Measurement ,ibuprofen ,business.industry ,030208 emergency & critical care medicine ,General Medicine ,Emergency department ,Regimen ,medicine.anatomical_structure ,Pediatrics, Perinatology and Child Health ,Sprains and Strains ,Emergency Medicine ,orthopedics ,Ankle ,pharmacology ,Emergency Service, Hospital ,business ,medicine.drug - Abstract
Objective We compared pain and degree of disability in patients with acute ankle sprains receiving regular scheduled ibuprofen versus pro re nata (PRN). Methods This study is a randomized single-blinded controlled trial of children aged 7 to 17 years presenting with acute ankle sprain to an emergency department. Patients were randomized to receive 10 mg/kg of ibuprofen per dose (maximum 600 mg) every 6 hours regular scheduled versus PRN. Outcome measures included a 100-mm visual analog scale pain and degree of disability at day 4. A sample size of 72 children had a power of 80% to detect a clinically meaningful difference of 20 mm between the regular and PRN group. Results We randomly assigned 99 patients to receive regular scheduled (n = 50) or PRN (n = 49) ibuprofen. Pain scores and degree of disability at day 4 showed no significant differences between groups. The rate of reported adverse effects was higher in the regular scheduled group (11.4% vs 9.5%) versus the PRN group. Conclusions Our study suggests that there is little benefit from routinely using a regular scheduled ibuprofen regimen for acute pediatric ankle sprains.
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- 2020
30. Child health care in Ukraine
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Michael J. Rieder
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business.industry ,Child health care ,Specialty ,International Medicine ,Primary care ,Medical care ,Tertiary care ,Nursing ,Pediatrics, Perinatology and Child Health ,Health care ,Medicine ,Postgraduate training ,business ,Soviet union - Abstract
Ukraineis a republic formed from someof the former Soviet Union's territory. Primary care for children in Ukraine is delivered by paediatricians in polyclinics. Specialty and tertiary care for children is based at children's hospitals, as is postgraduate training in paediatrics. Many challenges to child health care in Ukraine accompanied the collapse of the Soviet Union, includinga lack of resources devoted topublic health and community care, environmental contamination and a system of medical education and delivery of care that is not suited to meet evolving changes in medical care.L'Ukraine est une république formée d'une partie du territoire de l'ancienne Union soviétique. Dans ce pays, les soins de premier recours aux enfants sont assurés par des pédiatres situés dans des polycliniques. Les soins spécialisés et tertiaires sont offerts dans des hôpitaux pour enfants, de même que la formation surspécialisée en pédiatrie. De nombreux défis aux soins infantiles ont émergé en Ukraine par suite du démantèlement de l'Union soviétique, dont le manque de ressources vouées à la santé publique et aux soins communautaires, la contamination de l'environnement et un systême d’éducation médicale et de prestation des soins mal adapté pour répondre à l’évolution constante des soins médicaux.
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- 2020
31. Pharmacogenomics in Pediatric Oncology: Mitigating Adverse Drug Reactions While Preserving Efficacy
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Bruce Carleton, Michael J. Rieder, and Abdelbaset A. Elzagallaai
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0301 basic medicine ,medicine.medical_specialty ,Drug-Related Side Effects and Adverse Reactions ,medicine.medical_treatment ,Antineoplastic Agents ,Toxicology ,03 medical and health sciences ,0302 clinical medicine ,Neoplasms ,medicine ,Humans ,Dosing ,Adverse effect ,Intensive care medicine ,Child ,Cause of death ,Pharmacology ,Chemotherapy ,business.industry ,Cancer ,medicine.disease ,Clinical trial ,030104 developmental biology ,Pharmacogenetics ,030220 oncology & carcinogenesis ,Pharmacogenomics ,Child, Preschool ,business - Abstract
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 adverse effects of chemotherapy still affect most survivors of childhood cancer. Pharmacogenetics plays a major role in predicting the safety of cancer chemotherapy and, in the future, its effectiveness. Treatment failure in childhood cancer—due to either serious adverse effects that limit therapy or the failure of conventional dosing to induce remission—warrants development of new strategies for treatment. Here, we summarize the current knowledge of the pharmacogenomics of cancer drug treatment in children and of statistically and clinically relevant drug–gene associations and the mechanistic understandings that underscore their therapeutic value in the treatment of childhood cancer.
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- 2020
32. Quantification and characterization of granulocyte macrophage colony-stimulating factor activated human peripheral blood mononuclear cells by fluorine-19 cellular MRI in an immunocompromised mouse model
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Olivia C. Sehl, Michael Smith, Jeffrey M. Gaudet, Michael J. Rieder, Corby Fink, T C Meagher, N A Sheikh, Paula J. Foster, Gregory A. Dekaban, and Jimmy D. Dikeakos
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medicine.medical_treatment ,Antigen presenting cell (APC) ,Cancer immunotherapy ,Fluorine-19 (19F) ,Granulocyte ,Peripheral blood mononuclear cell ,Pediatrics ,030218 nuclear medicine & medical imaging ,Mice ,03 medical and health sciences ,0302 clinical medicine ,In vivo ,medicine ,Animals ,Humans ,Macrophage ,Radiology, Nuclear Medicine and imaging ,Antigen-presenting cell ,Radiological and Ultrasound Technology ,business.industry ,Macrophage Colony-Stimulating Factor ,Granulocyte-Macrophage Colony-Stimulating Factor ,Fluorine ,General Medicine ,Immunotherapy ,Cellular magnetic resonance imaging (MRI) ,Magnetic Resonance Imaging ,medicine.anatomical_structure ,Granulocyte macrophage colony-stimulating factor ,030220 oncology & carcinogenesis ,Leukocytes, Mononuclear ,Cancer research ,business ,Granulocytes ,medicine.drug - Abstract
Purpose The purpose of this study was to test fluorine-19 (19F) cellular magnetic resonance (MRI) as a non-invasive imaging modality to track therapeutic cell migration as a surrogate marker of immunotherapeutic effectiveness. Materials and methods Human peripheral blood mononuclear cell- (PBMC)-derived antigen presenting cell (APC) were labeled with a 19F-perfluorocarbon (PFC) and/or activated with granulocyte macrophage colony-stimulating factor (GM-CSF). Viability, phenotype and cell lineage characterization preceded 19F cellular MRI of PFC+ PBMC under both pre-clinical 9.4 Tesla (T) and clinical 3T conditions in a mouse model. Results A high proportion of PBMC incorporated PFC without affecting viability, phenotype or cell lineage composition. PFC+ PBMC were in vivo migration-competent to draining and downstream lymph nodes. GM-CSF addition to culture increased PBMC migration to, and persistence within, secondary lymphoid organs. Conclusion 19F cellular MRI is a non-invasive imaging technique capable of detecting and quantifying in vivo cell migration in conjunction with an established APC-based immunotherapy model. 19F cellular MRI can function as a surrogate marker for assessing and improving upon the therapeutic benefit that this immunotherapy provides.
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- 2020
33. FRI0547 The Effect of Corrected Inflammation, Oxidative Stress and Endothelial Dysfunction on Fmd Levels in Patients with Selected Chronic Diseases: A Quasi-Experimental Study
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David Piskin, Fatih Akcay, Michael J. Rieder, Muhammet Fatih Demir, Rolando Cimaz, Erkan Demirkaya, Zeynep Demir, Mustafa Kemal Basarali, Micol Romano, Nuri Haksever, Murat Karaman, Mahmut Ilker Yilmaz, Abdelbaset A. Elzagallaai, and Melik Seyrek
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Male ,medicine.disease_cause ,Gastroenterology ,Pediatrics ,Antioxidants ,chemistry.chemical_compound ,Malondialdehyde ,Immunology and Allergy ,Medicine ,Endothelial dysfunction ,Omega-3 ,Proteinuria ,biology ,Fatty Acids ,Middle Aged ,Vasodilation ,Serum Amyloid P-Component ,medicine.anatomical_structure ,C-Reactive Protein ,Rheumatoid arthritis ,Female ,medicine.symptom ,Adult ,medicine.medical_specialty ,Endothelium ,Immunology ,Arginine ,General Biochemistry, Genetics and Molecular Biology ,Rheumatology ,Internal medicine ,Vascular ,Fatty Acids, Omega-3 ,Humans ,Morinda ,Aged ,Inflammation ,business.industry ,C-reactive protein ,medicine.disease ,Atherosclerosis ,Oxidative Stress ,chemistry ,Chronic Disease ,Dietary Supplements ,biology.protein ,Endothelium, Vascular ,business ,Asymmetric dimethylarginine ,Oxidative stress - Abstract
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 to morbidity complicating the course of many chronic diseases.Objectives:To evaluate the effect of anti-atherosclerotic liquid (AAL), anti-inflammatory capsules (AIC) and anti-oxidant liquid (AOL) supplementation on the flow-mediated dilatation (FMD), inflammatory, oxidative stress and endothelial dysfunction markers in patients with selected chronic diseasesMethods:We analyzed data of 178 patients from cohorts with selected chronic diseases (Rheumatoid arthritis, familial Mediterranean fever, DM type-2, Hypertension, Multiple sclerosis, Chronic obstructive pulmonary disease, Alzheimer disease and Cancer) in this quasi-experimental study. Endothelial dysfunction was determined by FMD and serum asymmetric dimethylarginine (ADMA) levels. Serum ADMA, high sensitive C-reactive protein (hs-CRP), serum PTX3, malondialdehyde (MDA), Cu/Zn-superoxide dismutase (Cu/Zn-SOD), glutathione peroxidase (GSH-Px) levels and FMD were studied in baseline and after 12 weeks of Morinda citrifolia (AAL, 3 ml once per day), omega-3 (AIC, 3 capsules once per day) and extract with Alaskan blueberry and 21 different red purple fruit vegetables (AOL, 30 ml once per day). Stepwise multivariate regression analysis evaluated the association of FMD with clinical and serologic parameters.Results:Serum ADMA, MDA, PTX3, hsCRP and albumin levels, and proteinuria were significantly decreased and CuZn-SOD, GSH-Px and FMD levels were significantly increased following AAL, AIC and AOL therapies. FMD was negatively correlated with serum ADMA, MDA, PTX3, hsCRP levels, SBP and DBP and positively correlated to CuZn-SOD and eGFR levels both at baseline and after the 12-weeks treatment period. Multivariate regression analysis revealed that ADMA and PTX3 levels were independently related to FMD both before and after AAL, AIC and AOL therapies (Table 1, Figure 1).Conclusion:Our study shows that serum ADMA, MDA, PTX3 levels are associated with endothelial dysfunction in patients with selected chronic diseases. Short-term AAL, AIC and AOL therapies significantly improves FMD and normalizes ADMA, PTX3, hsCRP and MDA. This may have implications for adjunctive therapy in a number of chronic disorders.References:[1] Yilmaz MI, Saglam M, Caglar K, Cakir E, Sonmez A, Ozgurtas T et al. The determinants of endothelial dysfunction in CKD: oxidative stress and asymmetric dimethylarginine. Am J Kidney Dis. 2006;47(1):42-50. doi:10.1053/j.ajkd.2005.09.029.Disclosure of Interests:None declared
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- 2020
34. The Effect of Corrected Inflammation, Oxidative Stress and Endothelial Dysfunction on Fmd Levels in Patients with Selected Chronic Diseases: A Quasi-Experimental Study
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Melik Seyrek, Muhammet Fatih Demir, Abdelbaset A. Elzagallaai, Fatih Akcay, Rolando Cimaz, Nuri Haksever, Mahmut Ilker Yilmaz, David Piskin, Mustafa Kemal Basarali, Micol Romano, Zeynep Demir, Michael J. Rieder, Erkan Demirkaya, and Murat Karaman
- Subjects
0301 basic medicine ,Male ,lcsh:Medicine ,02 engineering and technology ,medicine.disease_cause ,Gastroenterology ,Pediatrics ,Antioxidants ,chemistry.chemical_compound ,Clinical trials ,Rheumatic diseases ,Malondialdehyde ,Endothelial dysfunction ,lcsh:Science ,Cancer ,chemistry.chemical_classification ,Omega-3 ,Multidisciplinary ,Proteinuria ,Glutathione peroxidase ,Fatty Acids ,Endocrine system and metabolic diseases ,Middle Aged ,021001 nanoscience & nanotechnology ,Vasodilation ,Serum Amyloid P-Component ,C-Reactive Protein ,Female ,medicine.symptom ,0210 nano-technology ,Adult ,medicine.medical_specialty ,Inflammation ,Arginine ,Article ,03 medical and health sciences ,Internal medicine ,Vascular ,Fatty Acids, Omega-3 ,medicine ,Humans ,Endothelium ,Morinda ,Aged ,business.industry ,lcsh:R ,Albumin ,medicine.disease ,Atherosclerosis ,Oxidative Stress ,030104 developmental biology ,chemistry ,Chronic Disease ,Dietary Supplements ,lcsh:Q ,Endothelium, Vascular ,Asymmetric dimethylarginine ,business ,Neurological disorders ,Oxidative stress - Abstract
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 patients from cohorts with selected chronic diseases in this quasi-experimental study. Endothelial dysfunction was determined by flow-mediated dilatation (FMD) and asymmetric dimethylarginine (ADMA) levels. Serum ADMA, high sensitive C-reactive protein (hs-CRP), serum PTX3, malondialdehyde (MDA), Cu/Zn-superoxide dismutase (Cu/Zn-SOD), glutathione peroxidase (GSH-Px) levels and FMD were studied in baseline and after 12 weeks of Morinda citrifolia (anti-atherosclerotic liquid- AAL), omega-3 (anti-inflammatory capsules- AIC) and extract with Alaskan blueberry (anti-oxidant liquid- AOL). Stepwise multivariate regression analysis was used to evaluate the association of FMD with clinical and serologic parameters. Serum ADMA, MDA, PTX3, hsCRP and albumin levels, and proteinuria were significantly decreased while CuZn-SOD, GSH-Px and FMD levels were significantly increased following AAL, AIC and AOL therapies. The FMD was negatively correlated with serum ADMA, MDA, PTX3, and hsCRP levels and positively correlated with CuZn-SOD and eGFR levels. ADMA and PTX3 levels were independently related to FMD both before and after AAL, AIC and AOL therapies. Our study shows that serum ADMA, MDA, PTX3 levels are associated with endothelial dysfunction in patients with selected chronic diseases. In addition, short-term AAL, AIC and AOL therapies significantly improves a number of parameters in our cohort and can normalize ADMA, PTX3, hsCRP and MDA levels.
- Published
- 2020
35. Role of Oxidative Stress in Hypersensitivity Reactions to Sulfonamides
- Author
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Elham A. Sultan, Awatif M. Abuzgaia, Abdelbaset A. Elzagallaai, Michael J. Rieder, John R. Bend, and Eman Loubani
- Subjects
Male ,Sulfamethoxazole ,Pharmacology ,medicine.disease_cause ,030226 pharmacology & pharmacy ,Pediatrics ,Lipid peroxidation ,Protein Carbonylation ,chemistry.chemical_compound ,0302 clinical medicine ,Anti-Infective Agents ,sulfamethoxazole hydroxylamine ,Pharmacology (medical) ,Lymphocytes ,Child ,chemistry.chemical_classification ,education.field_of_study ,adverse drug reactions ,Sulfonamides ,Drug Tolerance ,Middle Aged ,Glutathione ,Healthy Volunteers ,in vitro diagnosis ,030220 oncology & carcinogenesis ,Female ,Adult ,Blood Platelets ,Programmed cell death ,Adolescent ,Patients ,Cell Survival ,Necroptosis ,Population ,idiosyncratic drug reactions ,Peripheral blood mononuclear cell ,Drug Hypersensitivity ,03 medical and health sciences ,Young Adult ,medicine ,Humans ,education ,Aged ,Reactive oxygen species ,Oxidative Stress ,chemistry ,Leukocytes, Mononuclear ,Lipid Peroxidation ,Reactive Oxygen Species ,Oxidative stress ,drug allergy - Abstract
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 (sulfamethoxazole [SMX] hydroxylamine [SMX-HA] and SMX N-nitrosamine [SMX-NO]) is thought to be a major factor. These reactive metabolites contribute to the formation of reactive oxygen species (ROS) known to cause cellular damage and induce cell death through apoptosis and necroptosis. ROS can also serve as "danger signals," priming immune cells to mount an immunological reaction. We recruited 26 sulfa-hypersensitive (HS) patients, 19 healthy control subjects, and 6 sulfa-tolerant patients to this study. Peripheral blood monocytes and platelets were isolated from blood samples and analyzed for in vitro cytotoxicity, ROS and carbonyl protein formation, lipid peroxidation, and GSH (glutathione) content after challenge with SMX-HA. When challenged with SMX-HA, cells isolated from sulfa-HS patients exhibited significantly (P ≤ .05) higher cell death, ROS and carbonyl protein formation, and lipid peroxidation. In addition, there was a high correlation between cell death in PBMCs and ROS levels. There was also depletion of GSH and lower GSH/GSSG ratios in peripheral blood mononuclear cells from sulfa-HS patients. The amount of ROS formed was negatively correlated with intracellular GSH content. The data demonstrate a major role for oxidative stress in in vitro cytotoxicity of SMX reactive metabolites and indicate increased vulnerability of cells from sulfa-HS patients to the in vitro challenge.
- Published
- 2020
36. L’importance de l’apport alimentaire en sodium chez les enfants
- Author
-
Manjula Gowrishankar, Michael J. Rieder, and Becky Blair
- Subjects
0301 basic medicine ,030109 nutrition & dietetics ,Traditional medicine ,business.industry ,Sodium ,Salt ,chemistry.chemical_element ,Preventive health ,Diet ,03 medical and health sciences ,0302 clinical medicine ,chemistry ,Hypertension ,Pediatrics, Perinatology and Child Health ,Blood pressure ,Medicine ,030212 general & internal medicine ,business ,Children ,Nutrition ,Position Statements / Documents de Principes - Abstract
Résumé L’organisme a besoin de très petites quantités de sodium alimentaire pour soutenir le volume sanguin et la tension artérielle. Selon les données de surveillance nutritionnelle disponibles, la plupart des enfants canadiens consomment une quantité de sodium supérieure à leurs besoins nutritionnels. Environ 80 % du sodium que consomment les Canadiens proviennent d’aliments transformés et emballés. Chez les enfants, un fort apport en sodium peut être indicateur d’un régime alimentaire de piètre qualité. Les résultats d’analyses systématiques et de méta-analyses démontrent que la diminution du sodium alimentaire chez les enfants entraîne une réduction modeste, mais cliniquement non significative, de la tension artérielle. Les stratégies en population pour limiter la consommation de sodium, telles que la reformulation des produits alimentaires, la modification des processus d’approvisionnement alimentaire et les politiques fédérales de saine alimentation, sont d’importantes initiatives en santé publique qui peuvent réduire considérablement la consommation de sodium et contribuer à prévenir des maladies chroniques à l’âge adulte.
- Published
- 2020
37. Cytochrome P450
- Author
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Abdelbaset A. Elzagallaai and Michael J. Rieder
- Published
- 2020
38. Key potentially inappropriate drugs in pediatrics: The kids list
- Author
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David C. Knoppert and Michael J. Rieder
- Subjects
Medical education ,Editorial ,business.industry ,Pediatrics, Perinatology and Child Health ,Key (cryptography) ,Medicine ,Pharmacology (medical) ,business - Published
- 2020
39. Adverse Drug Reactions Across the Age Continuum: Epidemiology, Diagnostic Challenges, Prevention, and Treatments
- Author
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Michael J. Rieder
- Subjects
Drug ,Aging ,medicine.medical_specialty ,Drug-Related Side Effects and Adverse Reactions ,media_common.quotation_subject ,MEDLINE ,Pediatrics ,030226 pharmacology & pharmacy ,03 medical and health sciences ,0302 clinical medicine ,Pharmacotherapy ,Epidemiology ,Humans ,Medicine ,Pharmacology (medical) ,030212 general & internal medicine ,Drug reaction ,Child ,Intensive care medicine ,media_common ,Pharmacology ,business.industry ,Legislation, Drug ,3. Good health ,Pharmacogenomics ,Drug dosing ,business - Abstract
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. There are groups of children, notably those with complex and chronic diseases, who are at substantial risk for ADRs. The evaluation of an undesired effect during therapy is ideally accomplished by an organized approach that is a skill that clinicians who care for children-especially those children at high risk for ADRs must have. Additionally, clinicians as well as drug regulatory agencies and industry need to be both vigilant and astute as well as aware that ADRs in children are often different in nature and frequency from those in adults. The increasing use of pharmacogenomics to guide drug dosing and the increasing number of biological agents will provide new sets of challenges to clinicians over the next decade.
- Published
- 2018
40. SJS/TEN 2019: From science to translation
- Author
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Sonia Whyte-Croasdaile, Ricardo Cibotti, Hongsheng Wang, Ulrike Dehaeck, Munir Pirmohamed, Charles S. Bouchard, Cristina Olteanu, Sabine Straus, Karen Dewar, Christine Shieh, Hajirah N. Saeed, Neil H. Shear, Rannakoe J. Lehloenya, Esther Fuchs, Jessica Weintraub, Jean McCawley, Bruce Carleton, Maja Mockenhaupt, Zhao Qing Wang, Chia Ling Hsieh, Mee Kum Kim, Mayumi Ueta, Wan-Chun Chang, Sherrie J. Divito, Cynthia Sung, Wanpen Anderson, Angie Lowe, Alfonso Iovieno, Chonlaphat Sukasem, James H. Holmes, Sonia N. Yeung, Chen Wan, Sophie Le Pallec, Kristina B. Williams, Nicole Chapman, Elizabeth J. Phillips, Katie Niemeyer, Michael A. Norcross, Julie McCawley, Diane Forbes, Hyon K. Choi, Sheng Ying Tsou, Li Zhou, Michael R. Ardern-Jones, James Chodosh, Paul Anderson, Shuen-Iu Hung, David M. Koelle, Cindy Whale, Jennifer L. Goldman, Mario E. Lacouture, Thomas M. Beachkofsky, Elyse A. Hope, Riichiro Abe, Douglas Oboh, Robyn Lim, Agnieszka K. Biala, Jonathan Peter, Jason A Trubiano, Julienne Jagdeo, Galen E.B. Wright, Michael J. Rieder, Wen-Hung Chung, Mahyar Etminan, Teresa Bellón, Lisa M. Wheatley, Robert G. Micheletti, Gianpiero L. Cavalleri, Simona Volpi, and Helena B. Pasieka
- Subjects
0301 basic medicine ,medicine.medical_specialty ,International Cooperation ,Dermatology ,Disease ,Global Health ,Pediatrics ,Biochemistry ,Patient care ,Article ,Global Burden of Disease ,Translational Research, Biomedical ,030207 dermatology & venereal diseases ,03 medical and health sciences ,0302 clinical medicine ,Pharmacovigilance ,Global health ,Medicine ,Humans ,Registries ,Intensive care medicine ,Translational Medical Research ,Molecular Biology ,Patient Care Team ,Health Services Needs and Demand ,Patient care team ,integumentary system ,business.industry ,Congresses as Topic ,medicine.disease ,Toxic epidermal necrolysis ,3. Good health ,stomatognathic diseases ,030104 developmental biology ,Epidermal necrosis ,Pharmacogenetics ,Stevens-Johnson Syndrome ,business - Abstract
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 SJS/TEN as an uncommon but high burden disease will be necessary to improve efforts in prevention, early diagnosis and improved acute and long-term management. SJS/TEN 2019: From Science to Translation was a 1.5-day scientific program held April 26-27, 2019, in Vancouver, Canada. The meeting successfully engaged clinicians, researchers, and patients and conducted many productive discussions on research and patient care needs.
- Published
- 2019
41. Pharmacokinetic studies in children: recommendations for practice and research
- Author
-
Saskia N. de Wildt, Allison C. Needham, Joseph F. Standing, Lauren E. Kelly, Lauren Hanly Faught, Charlotte I. S. Barker, Martin Offringa, Michael J. Rieder, and Pediatric Surgery
- Subjects
Aging ,medicine.medical_specialty ,Biomedical Research ,Pharmacological research ,Models, Biological ,neonatology ,030226 pharmacology & pharmacy ,Pediatrics ,Specimen Handling ,law.invention ,paediatrics ,03 medical and health sciences ,0302 clinical medicine ,Pharmacotherapy ,Drug Therapy ,law ,030225 pediatrics ,Humans ,Medicine ,Pharmacokinetics ,Dosing ,Child ,Intensive care medicine ,pharmacometrics ,Evidence-Based Medicine ,Clinical pharmacology ,Dose-Response Relationship, Drug ,business.industry ,Clinical study design ,dosing ,Pharmacometrics ,3. Good health ,Research Design ,Pediatrics, Perinatology and Child Health ,pharmacology ,Renal disorders Radboud Institute for Health Sciences [Radboudumc 11] ,business - Abstract
Contains fulltext : 193438.pdf (Publisher’s version ) (Open Access) 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 understanding the dose-concentration-effect relationship and should underpin dosing recommendations, this review examines how challenges affecting the design and conduct of paediatric pharmacological studies can be overcome using targeted pharmacometric strategies. Model-based approaches confer benefits at all stages of the drug life-cycle, from identifying the first dose to be used in children, to clinical trial design, and optimising the dosing regimens of older, off-patent medications. To benefit patients, strategies to ensure that new PK, PD and trial data are incorporated into evidence-based dosing recommendations are needed. This review summarises practical strategies to address current challenges, particularly the use of model-based (pharmacometric) approaches in study design and analysis. Recommendations for practice and directions for future paediatric pharmacological research are given, based on current literature and our joint international experience. Success of PK research in children requires a robust infrastructure, with sustainable funding mechanisms at its core, supported by political and regulatory initiatives, and international collaborations. There is a unique opportunity to advance paediatric medicines research at an unprecedented pace, bringing the age of evidence-based paediatric pharmacotherapy into sight.
- Published
- 2018
42. Size and Taste Matters: Recent Progress in the Development of Age-Appropriate Medicines for Children
- Author
-
Michael J. Rieder
- Subjects
Pharmacology ,Drug ,medicine.medical_specialty ,Emerging technologies ,business.industry ,media_common.quotation_subject ,Pharmacology toxicology ,Age appropriate ,Pediatrics ,030226 pharmacology & pharmacy ,Drug formulations ,3. Good health ,Young infants ,03 medical and health sciences ,0302 clinical medicine ,030225 pediatrics ,medicine ,Polymer coating ,Pharmacology (medical) ,Taste masking ,Intensive care medicine ,business ,media_common - Abstract
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 acceptability. Medication acceptability in children is complex relating to a wide range of factors, including drug palatability. Over the past decade there has been an increasing interest in and research as to how to improve and enhance child-specific drug formulations including the development of specific instruments for assessing drug palatability in children and new approaches to teaching medication literacy to families. Approaches to enhancing drug acceptability have also included organoleptic (taste masking) strategies as well as the creation of a number of innovative taste-blocking strategies and new technologies for formulation preparation. Polymer coating, microencapsulation and heat melt technologies have resulted in drug formulations that are now being assessed in children while soft melt and gel formulations are now commonly used. Mini-tablets offer the potential of using solid delivery systems in even very young infants. This work has resulted in a number of highly promising developments that are being evaluated for clinical use as well as providing insights into new directions in pursuit of the common goal of effective and safe drug therapy for children. On-going challenges include the need for drug regulatory agencies to work closely with drug regulatory agencies in facilitating innovation in formulation design and approval.
- Published
- 2017
43. Adverse Drug Reactions in Children: The Double-Edged Sword of Therapeutics
- Author
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Mje Greff, Abdelbaset A. Elzagallaai, and Michael J. Rieder
- Subjects
Adult ,medicine.medical_specialty ,Pediatrics ,Adolescent ,Drug-Related Side Effects and Adverse Reactions ,Off-label use ,Risk Assessment ,030226 pharmacology & pharmacy ,03 medical and health sciences ,Child Development ,0302 clinical medicine ,Pharmacotherapy ,Drug Therapy ,Risk Factors ,Terminology as Topic ,Epidemiology ,medicine ,Humans ,Pharmacokinetics ,Pharmacology (medical) ,030212 general & internal medicine ,Practice Patterns, Physicians' ,Child ,Pharmacology ,business.industry ,Mortality rate ,Age Factors ,Infant, Newborn ,Infant ,Off-Label Use ,Child mortality ,Pharmaceutical Preparations ,Drug development ,Pharmacogenetics ,Child, Preschool ,Child Mortality ,Pharmacology, Clinical ,business ,Risk assessment - Abstract
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 latter less common but often severe and clinically more problematic due to their unpredictable nature and occurrence at any dose. Pediatric populations are especially vulnerable to ADRs due to the lack of data for this age group from the drug development process and because of the wide use of off-label and unlicensed use of drugs. Children are more prone to specific types of ADRs because of the level of maturity of body systems involved in absorption, metabolism, transportation, and elimination of drugs. This state-of-the-art review provides an overview of definitions, classifications, epidemiology, and pathophysiology of ADRs and discusses the available evidence for related risk factors and causes of ADRs in the pediatric population.
- Published
- 2017
44. How important is personality in the selection of medical school students?
- Author
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Tracy Mestdagh, Mitchell G. Rothstein, Matthew J. W. McLarnon, Deborah M. Powell, R. Blake Jelley, Amanda Poole, Richard D. Goffin, Michael J. Rieder, and Henryk T. Krajewski
- Subjects
Predictive validity ,020205 medical informatics ,media_common.quotation_subject ,02 engineering and technology ,Pediatrics ,0502 economics and business ,0202 electrical engineering, electronic engineering, information engineering ,Personality ,Range restriction ,General Psychology ,Selection (genetic algorithm) ,media_common ,Job performance ,4. Education ,05 social sciences ,Cognition ,Variance (accounting) ,Job analysis ,Selection tests ,Psychology ,Incremental validity ,050203 business & management ,Clinical psychology - Abstract
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. Successful performance as a medical student is determined by performance in courses and clinical rotations. The traditional cognitive predictors generally contribute to the prediction of course requirements. However, these traditional predictors often demonstrate weak relations with clinical performance, suggesting that other predictors are necessary. Using approximately 300 medical students, the current study investigated a) the ability of the traditional admission tools to predict course and clinical performance, and b) the incremental validity of personality predictors, which were chosen on the basis of a personality-oriented job analysis. The traditional predictors accounted for a significant proportion of variance in course performance, with personality accounting for incremental variance. Clinical performance was only predicted by personality and the traditional predictors did not demonstrate predictive validity.
- Published
- 2017
45. Oral morphine dosing predictions based on single dose in healthy children undergoing surgery
- Author
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Brian J. Anderson, Katherine A. Brand, Katarina Aleksa, Gideon Koren, Erin Cooke, Bruce Carleton, Michael J. Rieder, Pamela Winton, Gillian R. Lauder, Carolyne J. Montgomery, Ricardo Jimenez-Mendez, Joy Dawes, and Jacqueline A. Hannam
- Subjects
Oral ,Male ,medicine.medical_specialty ,Cmax ,Administration, Oral ,Opioid ,Pediatrics ,Enteral administration ,Mass Spectrometry ,Dose-Response Relationship ,03 medical and health sciences ,0302 clinical medicine ,Pharmacokinetics ,030202 anesthesiology ,030225 pediatrics ,medicine ,Humans ,Dosing ,Child ,Preschool ,Analgesics ,Chromatography ,Liquid ,Surgical Procedures ,Morphine ,Dose-Response Relationship, Drug ,business.industry ,Codeine ,Operative ,3. Good health ,Surgery ,Analgesics, Opioid ,Anesthesiology and Pain Medicine ,Child, Preschool ,Surgical Procedures, Operative ,Anesthesia ,Administration ,Pediatrics, Perinatology and Child Health ,Female ,Drug ,business ,Chromatography, Liquid ,medicine.drug ,Blood sampling - Abstract
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 profiles in children given common oral morphine dose regimens. Methods Children (2–6 years, n = 34) undergoing elective surgery and requiring opioid analgesia were randomized to receive preoperative oral morphine (100 mcg·kg−1, 200 mcg·kg−1, 300 mcg·kg−1). Blood sampling for morphine assay was performed at 30, 60, 90, 120, 180, and 240 min. Morphine serum concentrations were determined by liquid chromatography–mass spectroscopy and pharmacokinetic parameters were calculated using nonlinear mixed effects models. Current data were pooled with published time–concentration profiles from children (n = 1059, age 23 weeks postmenstrual age – 3 years) administered intravenous morphine, to determine oral bioavailability (F), absorption lag time (TLAG), and absorption half-time (TABS). These parameter estimates were used to predict concentrations in children given oral morphine (100, 200, 300, 400, 500 mcg·kg−1) at different dosing intervals (3, 4, 5, 6, 8, 12 h). Results The oral morphine formulation had F 0.298 (CV 36.5%), TLAG 0.45 (CV 63.6%) h and TABS 0.71 (CV 55%) h. A single-dose morphine 100 mcg·kg−1 achieved a mean CMAX 10 mcg·l−1. Repeat 4-hourly dosing achieved mean steady-state concentration 13–18 mcg·l−1; concentrations associated with good analgesia after intravenous administration. Serum concentration variability was large ranging from 5 to 55 mcg·l−1 at steady state. Conclusions Oral morphine 200 mcg·kg−1 then 100 mcg·kg−1 4 h or 150 mcg·kg−1 6 h achieves mean concentrations associated with analgesia. There was high serum concentration variability suggesting that respiration may be compromised in some children given these doses.
- Published
- 2016
46. Averting the foul taste of pediatric medicines improves adherence and can be lifesaving – Pheburane® (sodium phenylbutyrate)
- Author
-
Gideon Koren, Michael J. Rieder, and Yona Amitai
- Subjects
0301 basic medicine ,Drug ,medicine.medical_specialty ,Urea nitrogen ,business.industry ,Health Policy ,medicine.medical_treatment ,media_common.quotation_subject ,Medicine (miscellaneous) ,Sodium phenylbutyrate ,Bitter taste ,Gastrostomy ,03 medical and health sciences ,Pediatric Medicine ,030104 developmental biology ,0302 clinical medicine ,Lag time ,030225 pediatrics ,Medicine ,business ,Intensive care medicine ,Pharmacology, Toxicology and Pharmaceutics (miscellaneous) ,Social Sciences (miscellaneous) ,medicine.drug ,media_common - Abstract
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 highly foul taste, which often leads to children being unable to consume it, resulting in ineffective treatment, or alternatively, necessitating the application of the drug through a nasogastric tube or gastrostomy. METHODS This study reviews the published data on a novel formulation of NaPB, Pheburane® granules, which begin to release their NaPB after a lag time of ~10 seconds followed by a slow release over several minutes. RESULTS The taste-masked granule formulation of NaPB dramatically improves the acceptability of the drug by children and appears in initial studies to be both safe and effective. CONCLUSION While more studies are needed to substantiate and enrich these initial trials, the available data provide a telling example where masking the drug taste of medicine for children can sometimes be the difference between life and death.
- Published
- 2016
47. Authorizing medical cannabis for children
- Author
-
Michael J Rieder
- Subjects
medicine.medical_specialty ,Cannabinoids ,business.industry ,Pediatrics, Perinatology and Child Health ,Medical cannabis ,medicine ,Practical Tips for Paediatricians ,Psychiatry ,business ,Children ,Pediatrics - Published
- 2019
48. Pharmacy and pediatric drug therapy: The key to safe and effective treatment for children
- Author
-
Michael J. Rieder
- Subjects
Pharmacology ,medicine.medical_specialty ,Prescription Drugs ,Dose-Response Relationship, Drug ,Drug-Related Side Effects and Adverse Reactions ,business.industry ,Medication Therapy Management ,Health Policy ,Drug Compounding ,Age Factors ,Pharmacy ,Pharmacists ,Pediatric drug ,United States ,medicine ,Key (cryptography) ,Effective treatment ,Humans ,Drug Dosage Calculations ,Intensive care medicine ,business ,Child ,Pharmacy Service, Hospital - Published
- 2019
49. Consider If You Will: Proton Pump Inhibitors in Children, Infections, and Precision Medicine
- Author
-
Michael J. Rieder and Brian Hummel
- Subjects
medicine.medical_specialty ,medicine.drug_class ,Proton-pump inhibitor ,CYP2C19 ,Infections ,03 medical and health sciences ,0302 clinical medicine ,030225 pediatrics ,Internal medicine ,medicine ,Humans ,Precision Medicine ,Prescribed drugs ,Child ,Omeprazole ,Timoprazole ,business.industry ,Proton Pump Inhibitors ,Articles ,Precision medicine ,Infection rate ,Cytochrome P-450 CYP2C19 ,Phenotype ,Pediatrics, Perinatology and Child Health ,business ,medicine.drug - Abstract
OBJECTIVES: Proton pump inhibitors (PPIs) are often used in pediatrics to treat common gastrointestinal disorders, and there are growing concerns for infectious adverse events. Because CYP2C19 inactivates PPIs, genetic variants that increase CYP2C19 function may decrease PPI exposure and infections. We tested the hypothesis that CYP2C19 metabolizer phenotypes are associated with infection event rates in children exposed to PPIs. METHODS: This retrospective biorepository cohort study included individuals aged 0 to 36 months at the time of PPI exposure. Respiratory tract and gastrointestinal tract infection events were identified by using International Classification of Diseases codes in the year after the first PPI mention. Variants defining CYP2C19 *2, *3, *4, *8, *9, and *17 were genotyped, and all individuals were classified as CYP2C19 poor or intermediate, normal metabolizers (NMs), or rapid or ultrarapid metabolizers (RM/UMs). Infection rates were compared by using univariate and multivariate analyses. RESULTS: In all, 670 individuals were included (median age 7 months; 44% girls). CYP2C19 NMs (n = 267; 40%) had a higher infection rate than RM/UMs (n = 220; 33%; median 2 vs 1 infections per person per year; P = .03). There was no difference between poor or intermediate (n = 183; 27%) and NMs. In multivariable analysis of NMs and RM/UMs adjusting for age, sex, PPI dose, and comorbidities, CYP2C19 metabolizer status remained a significant risk factor for infection events (odds ratio 0.70 [95% confidence interval 0.50–0.97] for RM/UMs versus NMs). CONCLUSIONS: PPI therapy is associated with higher infection rates in children with normal CYP2C19 function than in those with increased CYP2C19 function, highlighting this adverse effect of PPI therapy and the relevance of CYP2C19 genotypes to PPI therapeutic decision-making.
- Published
- 2019
50. Twelve tips for enhancing student engagement
- Author
-
Harm Peters, Danai Wangsaturaka, Martin Wohlin, Manuel João Costa, Vishna Devi Nadarajah, Kulsoom Ghias, Antonio Celenza, Debra L. Klamen, Michael J. Rieder, Marko Zdravkovic, Margot Weggemans, Liz Mossop, and Universidade do Minho
- Subjects
Students, Medical ,Ciências da Educação [Ciências Sociais] ,020205 medical informatics ,Formative Feedback ,Best practice ,Medicina Básica [Ciências Médicas] ,Social Sciences ,Organizational culture ,Student engagement ,02 engineering and technology ,Peer support ,Pediatrics ,Peer Group ,Education ,Formative assessment ,03 medical and health sciences ,0302 clinical medicine ,0202 electrical engineering, electronic engineering, information engineering ,ComputingMilieux_COMPUTERSANDEDUCATION ,Humans ,030212 general & internal medicine ,Students ,Curriculum ,Medical education ,Science & Technology ,4. Education ,Work engagement ,Communication ,Research ,Peer group ,General Medicine ,Work Engagement ,Faculty ,Organizational Culture ,Ciências Sociais::Ciências da Educação ,Health Occupations ,Ciências Médicas::Medicina Básica ,Psychology - Abstract
Student engagement refers to a broad range of activities where students participate in management, education, research, and community activities within their institutions. It is a mutually beneficial collaborative approach between students and their institutions. This article provides practical advice for the implementation or further development of student engagement at medical, dental, and veterinary schools. The tips provided are based on the experiences of a group of universities recently recognized for best practice in student engagement, and are supported by evidence from the literature. The tips cover overarching themes which include the creation of an institutional culture and formal framework for student engagement, and maximize communication routes between students with peers and faculty. Tips are for specific areas of active student engagement, covering curriculum design and development, peer teaching, governance processes, research activities, peer support programs, and interaction with the local community., (undefined), info:eu-repo/semantics/acceptedVersion
- Published
- 2019
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