Publications by authors named "Adelle Atkinson"

36 Publications

Safety of administration of BNT162b2 mRNA (Pfizer-BioNTech) COVID-19 vaccine in youths and young adults with a history of acute lymphoblastic leukemia and allergy to PEG-asparaginase.

Pediatr Blood Cancer 2021 Aug 16:e29295. Epub 2021 Aug 16.

Division of Haematology/Oncology, The Hospital for Sick Children, Toronto, Ontario, Canada.

Vaccinationis a critical tool in the prevention of COVID-19 infection for individuals and for communities. The mRNA vaccines contain polyethylene glycol (PEG) as a stabilizer. Currently, in North America, only the BNT162b2 (Pfizer-BioNTech) mRNA vaccine is approved for individuals aged 12-17. Most patients treated with contemporary regimens for acute lymphoblastic leukemia receive PEG-asparaginase (PEG-ASNase) and 10%-30% will develop allergic reactions. Optimizing access and safety for vaccine administration for these patients is critical. This report describes a process developed to support COVID vaccination in a cohort of adolescents and young adults with a history of PEG-ASNase allergy.
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http://dx.doi.org/10.1002/pbc.29295DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8441639PMC
August 2021

Establishing Amoxicillin Allergy in Children Through Direct Graded Oral Challenge (GOC): Evaluating Risk Factors for Positive Challenges, Safety, and Risk of Cross-Reactivity to Cephalosporines.

J Allergy Clin Immunol Pract 2021 Jul 19. Epub 2021 Jul 19.

Division of Allergy and Clinical Immunology, Department of Pediatrics, Montreal Children's Hospital, Montreal, QC, Canada; Infectious Diseases and Immunity in Global Health Program, The Research Institute of the McGill University Health Centre, McGill University, Montreal, QC, Canada.

Background: Data on the diagnostic properties of direct oral challenges without the use of skin tests in children with suspected amoxicillin allergy are sparse.

Objective: Assess the use of direct oral challenges.

Methods: A cohort study was conducted between March 2013 and March 2020, in Montreal and Winnipeg. All children referred with reported history of benign reactions (ie, limited to the skin with no mucosal lesions and no vesicles) to amoxicillin were recruited and a 2-step graded oral challenge (GOC) was conducted. Data were collected on demographic characteristics, clinical characteristics, and comorbidities. Eligible children were followed to assess reactions to subsequent use of amoxicillin and to assess the safety of cephalexin use in children with a positive GOC.

Results: Among 1914 children recruited, 1811 (94.6%) tolerated the GOC, 42 (2.2%) developed mild immediate reactions, and 61 (3.2%) developed mild nonimmediate reactions. Among 265 participants who had a negative GOC and reused amoxicillin, 226 (85.3%) reported tolerance and 39 (14.7%) had mild cutaneous reactions. Chronic urticaria (adjusted odds ratio [aOR], 1.16; 95% CI, 1.09-1.23) and an index reaction occurring within 5 minutes of exposure (aOR, 1.09; 95% CI, 1.04-1.14) were associated with immediate reactions during the GOC. Symptoms lasting longer than 7 days (aOR, 1.05; 95% CI, 1.02-1.09) and parental drug hypersensitivity (aOR, 1.04; 95% CI, 1.03-1.06) were associated with nonimmediate reactions. Among those reacting to the GOC, 12.5% reacted with mild cutaneous reactions to cephalexin challenge.

Conclusions: Direct GOCs are an accurate and safe confirmatory to establish true hypersensitivity among children reporting benign reactions to amoxicillin.
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http://dx.doi.org/10.1016/j.jaip.2021.06.057DOI Listing
July 2021

Feedback and coaching.

Eur J Pediatr 2021 May 21. Epub 2021 May 21.

Department of Medical Education and Faculty Development, Isala Hospital, Isala Academy, Zwolle, the Netherlands.

If used thoughtfully and with intent, feedback and coaching will promote learning and growth as well as personal and professional development in our learners. Feedback is an educational tool as well as a social interaction between learner and supervisor, in the context of a respectful and trusting relationship. It challenges the learner's thinking and supports the learner's growth. Coaching is an educational philosophy dedicated to supporting learners' personal and professional development and growth and supporting them to reach their potential. In clinical education, feedback is most effective when it is explicitly distinguished from summative assessment. Importantly, feedback should be about firsthand observed behaviors (which can be direct or indirect) and not about information which comes from a third party. Learners are more receptive to feedback if it comes from a source that they perceive as credible, and with whom they have developed rapport. The coaching relationship between learner and supervisor should also be built on mutual trust and respect. Coaching can be provided in the moment (feedback on everyday clinical activities that leads to performance improvement, even with short interaction with a supervisor) and over time (a longer term relationship with a supervisor in which there is reflection on the learner's development and co-creation of new learning goals). Feedback and coaching are most valuable when the learner and teacher exhibit a growth mindset. At the organizational level, it is important that both the structures and training are in place to ensure a culture of effective feedback and coaching in the clinical workplace.Conclusions: Having a thoughtful and intentional approach to feedback and coaching with learners, as well as applying evidence-based principles, will not only contribute in a significant way to their developmental progression, but will also provide them with the tools they need to have the best chance of achieving competence throughout their training. What is Known: • Feedback and coaching are key to advancing the developmental progression of trainees as they work towards achieving competence. • Feedback is not a one-way delivery of specific information from supervisor to trainee, but rather a social interaction between two individuals in which trust and respect play a key role. • Provision of effective feedback may be hampered by confusing formative (supporting trainee learning and development) and summative (the judgment that is made about a trainee's level of competence) purposes. What is New: • Approaches to both the provision of feedback/coaching and the assessment of competence must be developed in parallel to ensure success in clinical training programs. • Faculty development is essential to provide clinical teachers with the skills to provide effective feedback and coaching. • Coaching's effectiveness relies on nurturing strong trainee-supervisor relationships, ensuring high-quality feedback, nourishing a growth mindset, and encouraging an institutional culture that embraces feedback and coaching.
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http://dx.doi.org/10.1007/s00431-021-04118-8DOI Listing
May 2021

Progressive decline of T and B cell numbers and function in a patient with CDC42 deficiency.

Immunol Res 2021 02 6;69(1):53-58. Epub 2021 Jan 6.

Division of Immunology and Allergy, Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, M5G 1X8, Canada.

Single allele mutations in the Cell Division Control protein 42 homolog (CDC42) gene were recently shown to cause Takenouchi-Kosaki syndrome with diverse manifestations. These include persistent mild thrombocytopenia with large platelet size, severe developmental delay, growth retardation, facial dysmorphism, and other neurodevelopmental and hematological anomalies. CDC42 deficiency might also cause myelofibrosis, myeloproliferation, and severe autoinflammation. CDC42 closely interacts with the Wiskott-Aldrich Syndrome Protein, but little is still known about the immune abnormalities associated with CDC42 deficiency. Detailed immune evaluations were performed in a patient diagnosed with a CDC42 Tyr64Cys mutation. The 19-year-old female suffered from recurrent pneumonia, otitis media, and bacteremia, which resolved at 10 years of age, concordant with the initiation of amoxicillin prophylaxis. In addition, the patient had frequent viral upper respiratory tract infections, which resolved without need for medical interventions. Immune evaluations demonstrated decreased immunoglobulin levels, inability to maintain antibody responses, progressive decline in the number of CD19+ B cells, and decreased switched memory B cells. There was also a decrease in CD4+ and CD8+ T cells, markedly reduced naïve T cells, and intermittent depressed proliferation of T cells to stimulation. Natural killer cells' number and functions were normal. However, no opportunistic infections were observed, nor was there evidence for autoinflammation. CDC42 deficiency might also be associated with decline in T and B cell function. Therefore, immunity in patients with CDC42 defects should be closely monitored, particularly among those with frequent infections or systemic autoinflammation.
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http://dx.doi.org/10.1007/s12026-020-09168-yDOI Listing
February 2021

Basophil activation test shows high accuracy in the diagnosis of peanut and tree nut allergy: The Markers of Nut Allergy Study.

Allergy 2021 06 29;76(6):1800-1812. Epub 2020 Dec 29.

Translational Medicine, Research Institute, Hospital for Sick Children, Toronto, ON, Canada.

Background: Peanut and tree nut allergies are the most important causes of anaphylaxis. Co-reactivity to more than one nut is frequent, and co-sensitization in the absence of clinical data is often obtained. Confirmatory oral food challenges (OFCs) are inconsistently performed.

Objective: To investigate the utility of the basophil activation test (BAT) in diagnosing peanut and tree nut allergies.

Methods: The Markers Of Nut Allergy Study (MONAS) prospectively enrolled patients aged 0.5-17 years with confirmed peanut and/or tree nut (almond, cashew, hazelnut, pistachio, walnut) allergy or sensitization from Canadian (n = 150) and Austrian (n = 50) tertiary pediatric centers. BAT using %CD63 basophils (SSClow/CCR3pos) as outcome was performed with whole blood samples stimulated with allergen extracts of each nut (0.001-1000 ng/mL protein). BAT results were assessed against confirmed allergic status in a blinded fashion to develop a generalizable statistical model for comparison to extract and marker allergen-specific IgE.

Results: A mixed effect model integrating BAT results for 10 and 100 ng/mL of peanut and individual tree nut extracts was optimal. The area under the ROC curve (AUROC) was 0.98 for peanut, 0.97 for cashew, 0.92 for hazelnut, 0.95 for pistachio, and 0.97 for walnut. The BAT outperformed sIgE testing for peanut or hazelnut and was comparable for walnut (AUROC 0.95, 0.94, 0.92) in a sub-analysis in sensitized patients undergoing OFC.

Conclusions: Basophil activation test can predict allergic clinical status to peanut and tree nuts in multi-nut-sensitized children and may reduce the need for high-risk OFCs in patients.
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http://dx.doi.org/10.1111/all.14695DOI Listing
June 2021

Differentiating Between β-Lactam-Induced Serum Sickness-Like Reactions and Viral Exanthem in Children Using a Graded Oral Challenge.

J Allergy Clin Immunol Pract 2021 02 6;9(2):916-921. Epub 2020 Sep 6.

Department of Pediatrics, Division of Allergy and Clinical Immunology, Montreal Children's Hospital, Montreal, Quebec, Canada.

Background: Serum sickness-like reactions (SSLRs) are defined by the presence of rash (primarily urticaria) and joint complaints (arthralgia/arthritis) that are believed to occur due to a non-IgE-mediated response to medications. However, similar reactions can occur due to viral infections, and it can be difficult to distinguish between the two. This may lead to unnecessary avoidance of the culprit antibiotic.

Objective: We aimed to evaluate children presenting with suspected SSLRs through a graded oral challenge (GOC).

Methods: All children referred to the Montreal Children's Hospital for potential antibiotic allergy (β-lactam or other antibiotics) and a clinical presentation compatible with SSLR were recruited for the study between March 2013 and February 2020. A standardized survey with questions on treatment, symptoms, and associated factors was completed, and a GOC (10% and subsequently 90% of the oral antibiotic dose) was conducted. Patients with a negative GOC were contacted annually to query on subsequent antibiotic use.

Results: Among 75 patients presenting with suspected SSLRs, the median age was 2.0 years and 46.7% were males. Most reactions were attributed to amoxicillin. Among the 75 patients, 2.7% reacted immediately (within 1 hour) to a GOC and 4.0% had a nonimmediate reaction. Of the 43 patients successfully contacted, 20 reported subsequent culprit antibiotic use of whom 25.0% had a subsequent mild reaction (macular/papular rash).

Conclusions: This is the first and largest pediatric study to assess SSLR using a GOC. Our findings suggest that using a GOC is safe and appropriate for differentiating between β-lactam-induced SSLR and viral exanthem in this population.
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http://dx.doi.org/10.1016/j.jaip.2020.08.047DOI Listing
February 2021

Diagnosis of Ibuprofen allergy through oral challenge.

Clin Exp Allergy 2020 05 3;50(5):636-639. Epub 2020 Apr 3.

Division of Pediatric Allergy and Clinical Immunology, McGill University Health Centre, Montreal, Quebec, Canada.

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http://dx.doi.org/10.1111/cea.13596DOI Listing
May 2020

Beta-lactam allergy in the paediatric population.

Paediatr Child Health 2020 Feb 6;25(1):62-63. Epub 2020 Feb 6.

Canadian Paediatric Society, Allergy Section, Ottawa, Ontario.

Beta-lactam allergy is commonly diagnosed in paediatric patients, but over 90% of individuals reporting this allergy are able to tolerate the medications prescribed after evaluation by an allergist. Beta-lactam allergy labels are associated with negative clinical and administrative outcomes, including use of less desirable alternative antibiotics, longer hospitalizations, increasing antibiotic-resistant infections, and greater medical costs. Also, children with true IgE-mediated allergy to penicillin medications are often advised to avoid all beta-lactam antibiotics, including cephalosporins, which is likely unnecessary in greater than 97% of those reporting penicillin allergies. Most patients can be safely treated with penicillin or amoxicillin if they do not have a history compatible with IgE-mediated or systemic, delayed reactions such as Stevens-Johnson syndrome (SJS), serum sickness-like reactions, drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome, or acute generalized exanthematous pustulosis (AGEP). Guidance is provided on how to stratify risk of beta-lactam allergy, and on test dosing and monitoring in the outpatient setting for patients deemed low risk. Guidance for patients at higher risk of beta-lactam allergy includes criteria for appropriate referral to allergists and the use of alternative antimicrobials, such as cephalosporins, while awaiting specialist assessment.
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http://dx.doi.org/10.1093/pch/pxz179DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7002816PMC
February 2020

The Importance of Delabeling β-Lactam Allergy in Children.

J Pediatr 2019 01 12;204:291-297.e1. Epub 2018 Oct 12.

Department of Pediatrics, Division of Allergy and Clinical Immunology, McGill University, Montreal, Quebec, Canada.

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http://dx.doi.org/10.1016/j.jpeds.2018.09.035DOI Listing
January 2019

Evaluation of an Ophthalmoscopy Simulator to Teach Funduscopy Skills to Pediatric Residents.

Can J Neurol Sci 2018 05 19;45(3):320-324. Epub 2018 Feb 19.

1Division of Neurology,The Hospital for Sick Children,University of Toronto,Toronto,ON,Canada.

Background: Medical school and residency training in ophthalmoscopic evaluation is limited, reducing diagnostic accuracy. We sought to evaluate the efficacy of self-study using an ophthalmoscopy simulator to improve the technical motor skills involved in direct funduscopy in postgraduate pediatric residents.

Methods: In this randomized-controlled study, 17 pediatric residents (postgraduate years 1-3) were randomized to control (n=8) or intervention (n=9) groups. Participants were asked to correctly identify the funduscopic findings presented to them on an ophthalmoscopy simulator after being trained on its use. Each participant was asked to review 20 images of the fundus, and then record their multiple-choice response on a scantron sheet listing all possible funduscopic pathologies. Pre- and post-intervention testing was performed. Survey data assessing exposure to funduscopy skills during undergraduate and postgraduate training and overall experience with the simulator were collected.

Results: Most (65% [11/17]) participants reported minimal or no formal teaching in ophthalmology during their undergraduate medical studies. Average pre-intervention score (of 20) was 10.24±1.75 (51%) for the entire group, with no statistically significant difference between average pre-score in the control (10.63±1.77) versus intervention (9.89±1.76, p=0.405) groups. Intervention subjects experienced a statistically significant improvement in scores (9.89±1.76 vs. 12.78±2.05, p=0.006 [95% confidence interval 4.80-0.98]), but control subjects did not.

Conclusions: A single session with an ophthalmoscopy simulator can improve diagnostic accuracy in postgraduate pediatric trainees. Use of ophthalmoscopy simulation represents a novel addition to traditional learning methods for postgraduate pediatric residents that can help trainees to improve their confidence and accuracy in performing this challenging examination.
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http://dx.doi.org/10.1017/cjn.2017.291DOI Listing
May 2018

Communicating wisely: teaching residents to communicate effectively with patients and caregivers about unnecessary tests.

BMC Med Educ 2017 Dec 11;17(1):248. Epub 2017 Dec 11.

Department of Medicine, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada.

Background: With rising healthcare costs and a focus on quality, there is a growing need to promote resource stewardship in medical education. Physicians need to be able to communicate effectively with patients/caregivers seeking tests and treatments that are unnecessary. This study aimed to evaluate the impact of an interactive workshop on residents' knowledge of resource stewardship and communication skills when counseling patients/caregivers about requests for unnecessary testing.

Methods: Participants were 83 Internal Medicine and Pediatrics residents at the University of Toronto in 2014-15. The evaluation compared resource stewardship knowledge and communication skills of 57 (69%) residents that attended the resource stewardship workshop to 26 residents (31%) who did not. Knowledge and communication skills assessment consisted of a written test and a structured assessment using standardized patient raters, respectively. A linear regression was applied to determine predictors of overall communication skills performance.

Results: Workshop attendance resulted in better performance on the knowledge test (4.3 ± 1.9 vs. 3.1 ± 1.7 out of 8, p = 0.01), but not better performance on the communication skills assessment (4.1 ± 0.8 vs. 4.0 ± 0.9 out of 5, p = 0.56). Higher training level (p = 0.01) and knowledge test scores (p = 0.046) were independent predictors of better overall communication skills, after adjusting for gender, training level, workshop attendance, knowledge and self-reported prior feedback on communication skills.

Conclusions: An interactive workshop can improve knowledge of resource stewardship, but improving communication skills with patients/caregivers about unnecessary testing may require additional training or reinforcement in the clinical learning environment. These teaching and assessment approaches can support the integration of education on resource stewardship into medical education.
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http://dx.doi.org/10.1186/s12909-017-1086-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5725805PMC
December 2017

Long-term immune reconstitution after matched unrelated hematopoietic stem cell transplantation for immunodeficiency.

J Allergy Clin Immunol 2018 03 8;141(3):1154-1157.e3. Epub 2017 Nov 8.

Division of Immunology & Allergy, Department of Paediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada; Canadian Centre for Primary Immunodeficiency, Toronto, Ontario, Canada; University of Toronto, Toronto, Ontario, Canada. Electronic address:

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http://dx.doi.org/10.1016/j.jaci.2017.10.015DOI Listing
March 2018

Combined immunodeficiency and atopy caused by a dominant negative mutation in caspase activation and recruitment domain family member 11 (CARD11).

J Allergy Clin Immunol 2018 05 19;141(5):1818-1830.e2. Epub 2017 Aug 19.

Division of Immunology and Allergy, Department of Pediatrics, Hospital for Sick Children and the University of Toronto, Toronto, Ontario, Canada; Canadian Centre for Primary Immunodeficiency and the Jeffrey Modell Research Laboratory for the Diagnosis of Primary Immunodeficiency, Hospital for Sick Children, Toronto, Ontario, Canada. Electronic address:

Background: Combined immunodeficiency (CID) is a T-cell defect frequently presenting with recurrent infections, as well as associated immune dysregulation manifesting as autoimmunity or allergic inflammation.

Objective: We sought to identify the genetic aberration in 4 related patients with CID, early-onset asthma, eczema, and food allergies, as well as autoimmunity.

Methods: We performed whole-exome sequencing, followed by Sanger confirmation, assessment of the genetic variant effect on cell signaling, and evaluation of the resultant immune function.

Results: A heterozygous novel c.C88T 1-bp substitution resulting in amino acid change R30W in caspase activation and recruitment domain family member 11 (CARD11) was identified by using whole-exome sequencing and segregated perfectly to family members with severe atopy only but was not found in healthy subjects. We demonstrate that the R30W mutation results in loss of function while also exerting a dominant negative effect on wild-type CARD11. The CARD11 defect altered the classical nuclear factor κB pathway, resulting in poor in vitro T-cell responses to mitogens and antigens caused by reduced secretion of IFN-γ and IL-2.

Conclusion: Unlike patients with biallelic mutations in CARD11 causing severe CID, the R30W defect results in a less profound yet prominent susceptibility to infections, as well as multiorgan atopy and autoimmunity.
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http://dx.doi.org/10.1016/j.jaci.2017.06.047DOI Listing
May 2018

Long-Term Outcome of Adenosine Deaminase-Deficient Patients-a Single-Center Experience.

J Clin Immunol 2017 Aug 26;37(6):582-591. Epub 2017 Jul 26.

Division of Immunology and Allergy, Hospital for Sick Children, Toronto, ON, M5G 1X8, Canada.

Purpose: Inherited defects in the adenosine deaminase (ADA) enzyme can cause severe combined immune deficiency (SCID) and systemic abnormalities. Management options for ADA-deficient patients include enzyme replacement therapy (ERT), hematopoietic stem cell transplantation (HSCT), and gene therapy (GT). Here, we describe the long-term benefits of these treatments.

Methods: Survival, infections, systemic sequelae, and laboratory assessments were recorded for all ADA-deficient SCID patients, managed at a single center since 1985, who survived 5 or more years following treatment.

Results: Of 20 ADA-deficient patients, the 8 (40%) who survived 5 or more years (range 6-29.5 years, median 14 years) were included in the study. Among the long-term survivors, two patients were treated exclusively with ERT, five underwent HSCT (three from HLA-matched sibling donors, two from HLA-mismatched related donors), and one received GT. The long-term survivors often suffered from recurrent respiratory infections; however, opportunistic infections occurred in only one patient. Systemic sequelae included lung disease such as bronchiectasis and asthma (four patients), neurologic abnormalities (six patients), metabolic disturbances (two patients), allergy and autoimmunity (six patients), and neoplasms (three patients). Normal CD4 T cell numbers and function, as well as antibody production, were usually observed after HSCT and GT, but not after ERT. Late deaths occurred in two patients at 15 and 25 years after HSCT, respectively, and were attributed to respiratory failure.

Conclusions: ADA-deficient patients commonly suffer from long-term complications, emphasizing the need for improved management and for multi-disciplinary follow-up.
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http://dx.doi.org/10.1007/s10875-017-0421-7DOI Listing
August 2017

Learning Through Experience: Influence of Formal and Informal Training on Medical Error Disclosure Skills in Residents.

J Grad Med Educ 2017 Feb;9(1):66-72

Background : Residents' attitudes toward error disclosure have improved over time. It is unclear whether this has been accompanied by improvements in disclosure skills.

Objective : To measure the disclosure skills of internal medicine (IM), paediatrics, and orthopaedic surgery residents, and to explore resident perceptions of formal versus informal training in preparing them for disclosure in real-world practice.

Methods : We assessed residents' error disclosure skills using a structured role play with a standardized patient in 2012-2013. We compared disclosure skills across programs using analysis of variance. We conducted a multiple linear regression, including data from a historical cohort of IM residents from 2005, to investigate the influence of predictor variables on performance: training program, cohort year, and prior disclosure training and experience. We conducted a qualitative descriptive analysis of data from semistructured interviews with residents to explore resident perceptions of formal versus informal disclosure training.

Results : In a comparison of disclosure skills for 49 residents, there was no difference in overall performance across specialties (4.1 to 4.4 of 5,  = .19). In regression analysis, only the current cohort was significantly associated with skill: current residents performed better than a historical cohort of 42 IM residents ( < .001). Qualitative analysis identified the importance of both formal (workshops, morbidity and mortality rounds) and informal (role modeling, debriefing) activities in preparation for disclosure in real-world practice.

Conclusions : Residents across specialties have similar skills in disclosure of errors. Residents identified role modeling and a strong local patient safety culture as key facilitators for disclosure.
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http://dx.doi.org/10.4300/JGME-D-16-00263.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5319631PMC
February 2017

Social pediatrics: weaving horizontal and vertical threads through pediatric residency.

BMC Med Educ 2017 Jan 13;17(1):12. Epub 2017 Jan 13.

Department of Paediatrics, University of Toronto, Toronto, ON, Canada.

Background: Social pediatrics teaches pediatric residents how to understand disease within their patients' social, environmental and political contexts. It's an essential component of pediatric residency training; however there is very little literature that addresses how such a broad-ranging topic can be taught effectively. The aim of this study was to determine and characterize social pediatric education in our pediatric residency training in order to identify strengths and gaps.

Methods: A social pediatrics curriculum map was developed, attending to 3 different dimensions: (1) the intended curriculum as prescribed by the Objectives of Training for Pediatrics of the Royal College of Physicians and Surgeons of Canada (RCPSC), (2) the formal curriculum defined by rotation-specific learning objectives, and (3) the informal/hidden curriculum as reflected in resident and teacher experiences and perceptions.

Results: Forty-one social pediatric learning objectives were extracted from the RCPSC Objectives of Training for Pediatrics, most were listed in the Medical Expert (51%) and Health Advocate competencies (24%). Almost all RCPSC social pediatric learning objectives were identified in more than one rotation and/or seminar. Adolescent Medicine (29.2%), Pediatric Ambulatory Medicine (26.2%) and Developmental Pediatrics (25%) listed the highest proportion of social pediatric learning objectives. Four (10%) RCPSC social pediatric objectives were not explicitly named within learning objectives of the formal curriculum. The informal curriculum revealed that both teachers and residents viewed social pediatrics as integral to all clinical encounters. Perceived barriers to teaching and learning of social pediatrics included time constraints, particularly in a tertiary care environment, and the value of social pediatrics relative to medical expert knowledge.

Conclusions: Despite the lack of an explicit thematic presentation of social pediatric learning objectives by the Royal College and residency training program, social pediatric topics are integrated, taught and learned throughout the entire curriculum. Special attention needs to be given to the hidden curriculum and system barriers that may impede social pediatric education.
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http://dx.doi.org/10.1186/s12909-016-0845-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5237183PMC
January 2017

Comparison of Immune Profiles in Fetal Hearts with Idiopathic Dilated Cardiomyopathy, Maternal Autoimmune-Associated Dilated Cardiomyopathy and the Normal Fetus.

Pediatr Cardiol 2016 Feb 20;37(2):353-63. Epub 2015 Oct 20.

Department of Pathology, Mount Sinai Hospital, Toronto, ON, Canada.

The etiology of idiopathic dilated cardiomyopathy (iDCM) remains unknown. Immune therapies have improved outcome in fetuses with DCM born to mothers with autoimmune disease (aDCM). The purpose of this retrospective study was to compare the myocardial B and T cell profiles in fetuses and neonates with idiopathic DCM (iDCM) versus autoimmune-mediated DCM (aDCM) and to describe the normal cell maturation within the human fetal myocardium. Of 60 fetal autopsy cases identified from institutional databases, 10 had aDCM (18-38 weeks), 12 iDCM (19-37 weeks) and 38 had normal hearts (11-40 weeks). Paraffin-embedded myocardium sections were stained for all lymphocyte (CD45), B cells (CD20, CD79a), T cells (CD3, CD4, CD7, CD8) and monocyte (CD68) surface markers. Two independent, blinded cell counts were performed. Normal hearts expressed all B and T cell markers in a bimodal fashion, with peaks at 22 and 37 weeks of gestation. The aDCM cohort was most distinct from normal hearts, with less overall T cell markers [EST -9.1 (2.6) cells/mm(2), p = 0.001], CD4 [EST -2.0 (0.6), p = 0.001], CD3 [EST -3.9 (1.0), p < 0.001], CD7 [EST -3.0 (1.1), p = 0.01] overall B cell markers [EST -4.9 (1.8), p = 0.01] and CD79a counts [EST -2.3 (0.9), p = 0.01]. The iDCM group had less overall B cell markers [EST -4.0 (1.8), p = 0.03] and CD79a [EST -1.7 (0.9), p = 0.05], but no difference in T cell markers. Autoimmune-mediated DCM fetuses have less B and T cell markers, whereas iDCM fetuses have less B cell markers compared with normal fetal hearts. The fetal immune system may play a role in the normal development of the heart and evolution of dilated cardiomyopathy.
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http://dx.doi.org/10.1007/s00246-015-1284-4DOI Listing
February 2016

Objective Evaluation of Otoscopy Skills Among Family and Community Medicine, Pediatric, and Otolaryngology Residents.

J Surg Educ 2016 Jan-Feb;73(1):129-35. Epub 2015 Sep 11.

Department of Otolaryngology-Head and Neck Surgery, The Hospital for Sick Children, University of Toronto, Toronto, Canada.

Introduction: The objective of this study is to evaluate and compare the perceived need for otolaryngology training and otoscopy diagnostic skills in primary care (Family and Community Medicine, Pediatric Medicine), and Otolaryngology Head and Neck Surgery (OTO-HNS) postgraduate trainees. Participant otoscopy skills were evaluated using the OtoSim simulator.

Methods: Family and Community Medicine, Pediatric, and OTO-HNS residents were recruited. Each resident participated in 3 separate otoscopy training and assessment sessions. The ability to correctly identify middle ear pathology was objectively evaluated using OtoSim™. Pretest, posttest, and 3-month retention test results were compared among residents in a paired comparison paradigm. Survey data assessing exposure to OTO-HNS during undergraduate and postgraduate training were also collected.

Results: A total of 57 residents participated in the study. All residents reported limited exposure to OTO-HNS during undergraduate medical training. Primary care trainees performed poorly on pretest assessments (30% ± 7.8%; 95% CI). Significant improvement in diagnostic accuracy was demonstrated following a single 1-hour teaching session (30%-62%; p < 0.001). Primary care residents demonstrated a significant decrease in diagnostic accuracy at a 3-month follow-up assessment (62%-52%, p < 0.001). Self-perceived comfort with otology was poorly correlated to pretest performance among primary care trainees (r = 0.26) and showed a stronger positive correlation among OTO-HNS trainees (r = 0.56).

Conclusions: A single teaching session with an otoscopy simulator significantly improved diagnostic accuracy in primary care and OTO-HNS trainees. Improved performance is susceptible to deterioration at 3 months if acquired skills are not frequently used. Self-perceived comfort with otology may not be an accurate predictor of otoscopic diagnostic skill.
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http://dx.doi.org/10.1016/j.jsurg.2015.07.011DOI Listing
November 2016

Rifampin hypersensitivity in a 2-year-old child with successful rapid oral desensitization.

Pediatr Infect Dis J 2014 Jul;33(7):787

Department of Pediatrics, Division of Allergy and Immunology, University of British Columbia, Vancouver Division of Allergy and Clinical Immunology, Hospital for Sick Children Department of Paediatrics, University of Toronto Division of Infectious Diseases, Hospital for Sick Children and University of Toronto, Toronto, Ontario, Canada.

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http://dx.doi.org/10.1097/INF.0000000000000295DOI Listing
July 2014

Case 2: Sepsis and shock in a term neonate.

Paediatr Child Health 2013 Nov;18(9):497-8

The Hospital for Sick Children, University of Toronto, Mount Sinai Hospital, Toronto, Ontario.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3885106PMC
November 2013

Dietary exposures and allergy prevention in high-risk infants: a joint position statement of the Canadian Society of Allergy and Clinical Immunology and the Canadian Paediatric Society.

Allergy Asthma Clin Immunol 2014 2;10(1):45. Epub 2014 Sep 2.

Department of Pediatrics, Dalhousie University, Division of Allergy, IWK Health Centre, Halifax, NS Canada.

Allergic conditions in children are a prevalent health concern in Canada. The burden of disease and the societal costs of proper diagnosis and management are considerable, making the primary prevention of allergic conditions a desirable health care objective. This position statement reviews current evidence on dietary exposures and allergy prevention in infants at high risk of developing allergic conditions. It revisits previous dietary recommendations for pregnancy, breastfeeding and formula-feeding, and provides an approach for introducing solid foods to high-risk infants. While there is no evidence that delaying the introduction of any specific food beyond six months of age helps to prevent allergy, the protective effect of early introduction of potentially allergenic foods (at four to six months) remains under investigation. Recent research appears to suggest that regularly ingesting a new, potentially allergenic food may be as important as when that food is first introduced. This article has already been published (Paediatr Child Health. 2013 Dec;18(10):545-54), and is being re-published with permission from the original publisher, the Canadian Paediatric Society.
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http://dx.doi.org/10.1186/1710-1492-10-45DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4407306PMC
April 2015

Diagnosing the learner in difficulty.

Pediatrics 2013 Aug 15;132(2):210-2. Epub 2013 Jul 15.

Hospital for Sick Children, Toronto, Ontario, Canada.

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http://dx.doi.org/10.1542/peds.2013-1526DOI Listing
August 2013

Antibiotic skin testing accompanied by provocative challenges in children is a useful clinical tool.

Allergy Asthma Clin Immunol 2013 Jun 14;9(1):22. Epub 2013 Jun 14.

Section of Clinical Immunology and Allergy, Department of Pediatrics, Alberta Children's Hospital and University of Calgary, 2888 Shaganappi Trail NW, Calgary, Alberta T3B 6A8, Canada.

Background: Diagnostic testing to antibiotics other than to penicillin has not been widely available, making the diagnosis of antibiotic allergy difficult and often erroneous. There is often reluctance in performing challenges to antibiotics when standardized testing is lacking. However, while the immunogenic determinants are not known for most antibiotics, a skin reaction at a non-irritating concentration (NIC) may mean that antibodies to the native form are present in the circulation. While the NIC's for many non penicillin antibiotics have been determined in adults, the use of these concentrations for skin testing pediatric subjects prior to provocative challenge has not been done. Our objective was to determine if we could successfully uncover the true nature of antibiotic allergy in children using these concentrations for testing.

Methods: Children were included between 2003-2009 upon being referred to the Drug and Adverse Reaction/Toxicology (DART) clinic of the Hospital for Sick Children in Toronto, Ontario Canada. The referral needed to demonstrate that clinical care was being compromised by the limitation in antibiotic options or there was a significant medical condition for which the label of antibiotic allergy may prove detrimental. Patients were not seen if there was a suggestion of serum like sickness, Stevens Johnson Syndrome or Toxic Epidermal Necrolysis. Patients were excluded from testing if there was objective evidence of anaphylaxis. All other patients were consented to receive testing and/or challenges. A retrospective chart review was then performed of the results.

Results: We were able to exclude an antibiotic allergy in the majority of our patients who had a negative intradermal test result and were then challenged (>90%). Only one patient was challenged with a positive intradermal test to Cotrimoxazole because of a questionable history and this patient failed the provocative challenge. While we did not challenge more patients with positive testing, we did note that 10/11 (91%) patients with positive intradermal testing had some aspect of a Type 1 reaction in their history.

Conclusions: Through testing with NIC's of various antibiotics in children and providing provocative challenges based on negative skin testing results, we were able to advance the medical care of the majority of our patients by increasing their antibiotic options in order to successfully treat future infections. While challenging patients with positive testing was not deemed ethically appropriate at this stage of our study, it would be a useful future step to reaching statistical validity of testing to these antibiotics.
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http://dx.doi.org/10.1186/1710-1492-9-22DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3687567PMC
June 2013

No systemic reactions to influenza vaccination in egg-sensitized tertiary-care pediatric patients.

Allergy Asthma Clin Immunol 2012 Mar 2;8. Epub 2012 Mar 2.

Division of Immunology and Allergy, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.

Background: There are numerous, disparate guidelines for influenza vaccination in egg-allergic patients. We aimed to describe the outcome of selectively applied guidelines, based on risk-stratification, to our high risk, egg-allergic, tertiary-care pediatric population.

Methods: Egg allergy was confirmed with skin testing. The vaccine administered was an adjuvunated 2009 H1N1 influenza A vaccine with < 0.165 mcg/ml ovalbumin. Patients with mild egg allergy were to receive the vaccination in 1 dose, those with severe egg allergy were to receive 2 split doses, and patients with exquisite egg allergy or significant co-morbidities were to be skin tested with the vaccine (prick full strength, intradermal 1:100 of final concentration without adjuvant) and had 5 step desensitization if the testing was positive, or 1-2 step administration if negative. Patients were observed for 60 minutes after the final dose and anaphylaxis treatment was available. We report the frequency of allergic reactions.

Results: Ninety-nine patients were referred and 79 had positive egg testing. Asthma was present in 67% and 30% had prior anaphylaxis to egg. We vaccinated 77 of 79 patients: 71 without performing vaccine skin testing. Two refused vaccination. No patient had a systemic reaction or required treatment. Two patients experienced positive testing to the adjuvanated intradermal vaccine, but were negative without adjuvant.

Conclusions: Our results suggest that most egg-allergic tertiary care pediatric patients can be vaccinated with a low ovalbumin content influenza vaccine without prior vaccine testing. Vaccine skin testing, if used at all, can be reserved for special circumstances. The squalene adjuvant may cause an irritant reaction with intradermal testing.
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http://dx.doi.org/10.1186/1710-1492-8-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3313878PMC
March 2012

The myocardium of fetuses with endocardial fibroelastosis contains fewer B and T lymphocytes than normal control myocardium.

Pediatr Cardiol 2011 Dec 12;32(8):1088-95. Epub 2011 Apr 12.

The Hospital for Sick Children, Labatt Family Heart Centre, University of Toronto, Toronto, ON, M5G 1X8, Canada.

The observation that endocardial fibroelastosis (EFE) can result from an immune response to maternal autoantibody deposition in the fetal myocardium raises the possibility that the fetal immune system may contribute to the pathogenesis of idiopathic EFE and dilated cardiomyopathy (DCM). This study sought to characterize myocardial immune cell presence in fetuses and neonates with idiopathic EFE + DCM, in those with EFE + structural heart disease, and in normal control subjects. Paraffin tissue sections from fetuses identified from the pathology database were stained for B cell, T cell, macrophage, and general hematopoietic cell surface markers. Of the 14 fetuses included in the study, 5 had EFE + DCM, 4 had EFE + structural heart disease, and 5 were normal control fetuses. The EFE + DCM group had fewer B cells than the control group (0.15 vs. 0.44 cells/mm(2); p = 0.005). The EFE + heart disease group had both fewer B cells (0.18 vs. 0.44 cells/mm(2); p = 0.08) and T cells (0.29 vs. 0.80 cells/mm(2); p = 0.04) than the control group. The CD4/CD8 ratio was similar in the EFE + DCM and EFE + heart disease groups (1.0 vs. 0.9; p = 0.17) but higher in the EFE + DCM group than in the control group (0.9 vs. 0.3; p = 0.03). The myocardium of fetuses with EFE contains fewer B and T lymphocytes than normal control fetuses.
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http://dx.doi.org/10.1007/s00246-011-9980-1DOI Listing
December 2011

Safety of intravenous immunoglobulin in the treatment of juvenile dermatomyositis: adverse reactions are associated with immunoglobulin A content.

Pediatrics 2008 Mar 25;121(3):e626-30. Epub 2008 Feb 25.

Division of Rheumatology, Department of Pediatrics, University of Toronto, The Hospital for Sick Children, Toronto, Ontario, Canada.

Objective: Anecdotal reports have suggested differences in children's tolerance to different intravenous immunoglobulin products; however, there has been little research on this issue. We sought to determine whether different intravenous immunoglobulin products used in the treatment of juvenile dermatomyositis are equally well tolerated by patients and, if not, whether differences in tolerance are linked to immunoglobulin A content.

Patients And Methods: The intravenous immunoglobulin infusion history (product given and history of adverse events) of patients who were attending the juvenile dermatomyositis clinic at the Hospital for Sick Children from 1986 to 2005 was reviewed. Products with an immunoglobulin A content of >15 microg/mL were classified as "high immunoglobulin A." Data were analyzed by using logistic regression models adjusted for repeated measures.

Results: Thirty-eight patients with juvenile dermatomyositis received 1056 infusions at the Hospital for Sick Children. Adverse events were reported on 92 occasions (9%), affecting 25 patients (66%), a frequency that is higher than that usually reported in adult patients (<1%-5%). Adverse events were reported more often with products that contained high immunoglobulin A (15.0% vs 8.0%). These were accounted for specifically by fever (8.0% vs 1.0%), lethargy or malaise (2.0% vs 0.1%), and nausea or vomiting (5.0% vs 1.0%). Of the possible pharmacologic predictors, including dose, immunoglobulin G concentration, immunoglobulin A level, pH, glycine content, sugar content, sodium content, and osmolality, only immunoglobulin A level was significantly associated with adverse events.

Conclusions: Intravenous immunoglobulin was found to be safe and well tolerated by most children with juvenile dermatomyositis. However, in contrast to adult studies, we found that significant differences existed in tolerance to different intravenous immunoglobulin products, most likely because of immunoglobulin A concentration. This study confirms anecdotal reports that a high level of immunoglobulin A in intravenous immunoglobulin is less well tolerated by children and provides evidence that product choice is important in pediatrics.
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http://dx.doi.org/10.1542/peds.2007-1218DOI Listing
March 2008
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