13 research outputs found
Genome-wide identification and phenotypic characterization of seizure-associated copy number variations in 741,075 individuals
Copy number variants (CNV) are established risk factors for neurodevelopmental disorders with seizures or epilepsy. With the hypothesis that seizure disorders share genetic risk factors, we pooled CNV data from 10,590 individuals with seizure disorders, 16,109 individuals with clinically validated epilepsy, and 492,324 population controls and identified 25 genome-wide significant loci, 22 of which are novel for seizure disorders, such as deletions at 1p36.33, 1q44, 2p21-p16.3, 3q29, 8p23.3-p23.2, 9p24.3, 10q26.3, 15q11.2, 15q12-q13.1, 16p12.2, 17q21.31, duplications at 2q13, 9q34.3, 16p13.3, 17q12, 19p13.3, 20q13.33, and reciprocal CNVs at 16p11.2, and 22q11.21. Using genetic data from additional 248,751 individuals with 23 neuropsychiatric phenotypes, we explored the pleiotropy of these 25 loci. Finally, in a subset of individuals with epilepsy and detailed clinical data available, we performed phenome-wide association analyses between individual CNVs and clinical annotations categorized through the Human Phenotype Ontology (HPO). For six CNVs, we identified 19 significant associations with specific HPO terms and generated, for all CNVs, phenotype signatures across 17 clinical categories relevant for epileptologists. This is the most comprehensive investigation of CNVs in epilepsy and related seizure disorders, with potential implications for clinical practice
GWAS meta-analysis of over 29,000 people with epilepsy identifies 26 risk loci and subtype-specific genetic architecture
Epilepsy is a highly heritable disorder affecting over 50 million people worldwide, of which about one-third are resistant to current treatments. Here we report a multi-ancestry genome-wide association study including 29,944 cases, stratified into three broad categories and seven subtypes of epilepsy, and 52,538 controls. We identify 26 genome-wide significant loci, 19 of which are specific to genetic generalized epilepsy (GGE). We implicate 29 likely causal genes underlying these 26 loci. SNP-based heritability analyses show that common variants explain between 39.6% and 90% of genetic risk for GGE and its subtypes. Subtype analysis revealed markedly different genetic architectures between focal and generalized epilepsies. Gene-set analyses of GGE signals implicate synaptic processes in both excitatory and inhibitory neurons in the brain. Prioritized candidate genes overlap with monogenic epilepsy genes and with targets of current antiseizure medications. Finally, we leverage our results to identify alternate drugs with predicted efficacy if repurposed for epilepsy treatment
Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study
Summary
Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally.
Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies
have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of
the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income
countries globally, and identified factors associated with mortality.
Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to
hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis,
exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a
minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical
status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary
intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause,
in-hospital mortality for all conditions combined and each condition individually, stratified by country income status.
We did a complete case analysis.
Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital
diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal
malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome
countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male.
Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3).
Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income
countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups).
Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome
countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries;
p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients
combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11],
p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20
[1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention
(ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety
checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed
(ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of
parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65
[0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality.
Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome,
middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will
be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger
than 5 years by 2030
Antenatal depression and children’s developmental outcomes: potential mechanisms and treatment options
During the last decade there has been increased recognition of the prevalence of antenatal depression as well as an expansion in research examining the impact of maternal mood during pregnancy on offspring development. The aim of this review was to summarise the theoretical underpinnings and empirical evidence regarding the impact of antenatal depression on children's developmental outcomes. Biological mechanisms hypothesised to account for an association between antenatal depression and adverse offspring outcomes are first identified including the functioning of the prenatal Hypothalamic Pituitary Adrenal (HPA) axis and epigenetic processes. A systematic literature search is then conducted of studies examining the impact of antenatal depression on child development. In general, studies examining associations between antenatal depression and offspring temperament, cognitive and emotional outcomes reveal either no effect of the prenatal environment or small effects that often attenuate following adjustment for other antenatal and postnatal risk factors. In contrast, an independent effect of antenatal depression on children's conduct problems and antisocial behaviour is a well-replicated finding. There is emerging evidence that exposure to depression during pregnancy impacts negatively on offspring biology, although the findings are complex and require replication. Psychological and pharmacological treatments of antenatal depression are then reviewed, considering whether antidepressant medication exerts harmful effects on the foetus. We close by proposing that antenatal depression is an early marker of a developmental cascade to future mental health problems for both mothers and offspring
Proceedings of the Canadian society of allergy and clinical immunology annual scientific meeting 2015
Table of contents
A1 Role of fibrocytes in allergic rhinitis
Marie-Ève Côté, Marie-Ève Boulay, Sophie Plante, Jamila Chakir, Louis-Philippe Boulet
A2 Patterns of aeroallergens sensitization in Northern Alberta
Hanan Ahmed, Maria-Beatriz Ospina, Kyriaki Sideri, Harissios Vliagoftis
A3 Addressing acceptable risk for adolescents with Food-Induced Anaphylaxis (FIA)
Sara F. Johnson, Roberta L. Woodgate
A4 Outcomes of matched related and unrelated bone marrow transplantation after reduced-toxicity conditioning for children suffering from Chronic Granulomatous Disease
Guilhem Cros, Pierre Teira, Sonia Cellot, Henrique Bittencourt, Helene Decaluwe, Marie France Vachon, Michel Duval, Elie Haddad
A5 Outcomes of patients with severe combined immunodeficiency (SCID) prior to and after initiation of newborn screening for SCID in Ontario
Vy H.D. Kim, Anne Pham-Huy, Eyal Grunebaum
A6 Detection of regulatory B cells in the airways of subjects with asthma
John-Paul Oliveria, Stephanie Phan, Mark W. Tenn, Damian Tworek, Steven G. Smith, Adrian J. Baatjes, Caitlin D. Obminski, Caroline E. Munoz, Tara X. Scime, Roma Sehmi, Gail M Gauvreau
A7 Characterization of IgE-expressing B cells in the airways and peripheral blood of allergic asthmatic subjects
John-Paul Oliveria, Stephanie Phan, Mark W. Tenn, Brittany M Salter, Steven G Smith, Caitlin D Obminski, Caroline E Munoz, Abbey Schlatman, Tara X Scime, Rick Watson, Roma Sehmi, Gail M Gauvreau
A8 Pregnancy: could it be a risk factor for primary immunodeficient patients
Roya Sherkat, Razieh Khoshnevisan, Saba Sheikhbahaei
A9 Clinical experience with Octagam: a Canadian retrospective chart review
Stephen Betschel, Richard Warrington, Robert Schellenberg
A10 Kounis syndrome secondary to contrast media with inferior ST elevations and bilateral ischemic stroke
Michael N Fein, Jean-Philippe Pelletier
A11 Honey bee venom immunotherapy ineffective in bumble bee-induced anaphylaxis: case report and review of literature
Manstein Kan, Robert Schellenberg
A12 Delayed immune reconstitution occurring after multiple immune complications of hematological stem cell transplantation for a leaky SCID
Roxane Labrosse, Guilhem Cros, Pierre Teira, Henrique Bittencourt, Helene Decaluwe, Michel Duval, Elie Haddad
A13 Comparison of Three Case Reports of Acquired Angioedema: presentation, management and outcome
Raymond Mak, James Loh, Amin Kanani
A14 Sitagliptin-associated angioedema not related to concurrent use of ARB or ACE inhibitor
Dominik A. Nowak, Paul K. Keith
A15 Sneddon-Wilkinson subcorneal pustular dermatosis associated with an IgA monoclonal gammopathy
Daniel Pannozzo, Dominik A. Nowak, Hermenio C. Lima
A16 Omalizumab can be effective in patients with allergic bronchopulmonary aspergillosis
Diana Pham, Hoang Pham, Gonzalo G. Alvarez, Istvan T. Bencze, Krishna B. Sharma, Mark Smith, Shawn Aaron, Jennifer Block, Tara Keays, Judith Leech, David Schneidermen, Jodi Cameron, Jennifer Forgie, Alicia Ring, John W. O’Quinn, Stephanie Santucci, William H. Yang
A17 Efficacious use of omalizumab in the treatment of cystic fibrosis
Diana Pham, Hoang Pham, Ena Gaudet, Shawn Aaron, Stephanie Santucci, William H. Yang
A18 HAE with normal C1-INH with inconsistent response to C1 esterase inhibitor infusion but reliably responsive to icatibant
Hoang Pham, Stephanie Santucci, William H. Yang
A19 Anaphylaxis reaction to lactase enzyme
Mathew R. Voisin, Rozita Borici-Mazi
A20 Risk of solid tumor malignancies in patients with primary immune deficiency
Kateryna Vostretsova, Donald F. Stark
A21 Is it time to adopt the chromogenic assay for measuring C1 esterase inhibitor function in patients with HAE Type 2?
Elizabeth Yeboah, Paul K. Keith
A22 Emergency department visits for anaphylaxis and allergic reactions
Michelle Martin-Rhee, Cheryl Gula, Clare Cheng, Geoff Paltser
A23 START: Susceptibility To food Allergies in a Registry of Twins
Alizée Dery, Ann Clarke, Kari Nadeau, Laurie Harada, Kimberley Weatherall, Celia Greenwood, Denise Daley, Yuka Asai, Moshe Ben-Shoshan
A24 Qualifying the diagnostic approach employed by allergists when managing patients with self-diagnosed non-celiac gluten sensitivity (NCGS)
Lee Horgan, Teresa Pun
A25 Retrospective analysis on the agreement between skin prick test and serum food specific IgE antibody in adults with suspected food allergy
Ling Ling, Maria B. Ospina, Kyriaki Sideri, Harissios Vliagoftis
A26 Staple food hypersensitivity from infancy to adolescence: a report from the BAMSE cohort
Jennifer L.P. Protudjer, Mirja Vetander, Marianne van Hage, Ola Olén, Magnus Wickman, Anna Bergström
A27 Evaluating the impact of supervised epinephrine autoinjector administration during food challenges on perceived parent confidence
Timothy Teoh, Christopher Mill, Tiffany Wong, Ingrid Baerg, Angela Alexander, Kyla J. Hildebrand, John Dean, Boris Kuzeljevic, Edmond S. Chan
A28 Local immunoglobulin production to Aspergillus fumigatus cystic fibrosis
Jonathan Argeny, Mia Gona-Hoepler, Petra Fucik, Edith Nachbaur, Saskia Gruber, Reto Crameri, Andreas Glaser, Zsolt Szépfalusi, Claudio Rhyner, Thomas Eiwegger
A29 Extract consumption with skin prick test (SPT) devices
Greg. Plunkett, Brad Mire
A30 Evaluation of our cases with nonsteroidal anti-inflammatory drug reactions
Mehtap Yazicioglu, Ceren Can, Gokce Ciplak
A31 Reasons for referral and final diagnoses in a tertiary care pediatric allergy clinic
Victoria E. Cook, Kyla J. Hildebrand, Elodie Portales-Casamar, Christopher Mill, Edmond S. Chan
A32 Internist referral practices for inpatients with self-reported penicillin allergies at a tertiary care teaching hospital
Michael N Fein, Emil P Nashi
A33 Assessing the risk of reactions in children with a negative oral challenge after a subsequent use of amoxicillin
Sofianne Gabrielli, Christopher Mill, Marie-Noel Primeau, Christine Lejtenyi, Elena Netchiporouk, Alizee Dery, Greg Shand, Moshe Ben-Shoshan
A34 Validity of self-reported penicillin allergies
Erica Hoe, Joel Liem
A35 Effectiveness of allergy-test directed elimination diets in eosinophilic esophagitis
Jason K. Ko, David J.T. Huang, Jorge A. Mazza
A36 Allergy testing and dietary management in pediatric eosinophilic esophagitis (EoE): A retrospective review of a tertiary Canadian centre’s experience
Mary McHenry, Anthony Otley,Wade Watson
A37 Visualizing the impact of atopic and allergic skin disease
Dominik A. Nowak, John N. Kraft
A38 Cystic fibrosis with and without nasal polyposis in pediatric patients: a cross-sectional comparative study
Mihaela Paina, Ahmed A. Darwish Hassan, Delia Heroux, Lynn Crawford, Gail Gauvreau, Judah Denburg, Linda Pedder, Paul K. Keith
A39 Evaluation of macrolide antibiotic hypersensitivity: the role of oral challenges in children
Bahar Torabi, Marie-Noel Primeau, Christine Lejtenyi, Elaine Medoff, Jennifer Mill, Moshe Ben-Shoshan
A40 Venom allergy testing: is a graded approach necessary?
Jaclyn A. Quirt, Xia Wen, Jonathan Kim, Angel Jimenez Herrero, Harold L. Kim
A41 The role of oral challenges in evaluating cephalosporin hypersensitivity reactions in children
Magdalena J. Grzyb, Marie-Noël Primeau, Christine Lejtenyi, Elaine Medoff, Jennifer Mill, Moshe Ben-Shoshan
A42 Breastfeeding and infant wheeze, atopy and atopic dermatitis: findings from the Canadian Healthy Infant Longitudinal Development Study
Meghan B. Azad, Zihang Lu, Allan B. Becker, Padmaja Subbarao, Piushkumar J. Mandhane, Stuart E. Turvey, Malcolm R. Sears, the CHILD Study Investigators
A43 IL33 DNA methylation in bronchial epithelial cells is associated to asthma
Anne-Marie Boucher-Lafleur, Valérie Gagné-Ouellet, Éric Jacques, Sophie Plante, Jamila Chakir, Catherine Laprise
A44 NRF2 mediates the antioxidant response to organic dust-induced oxidative stress in bronchial epithelial cells
Michael Chen, Toby McGovern, Mikael Adner, James G. Martin
A45 The effects of perinatal distress, immune biomarkers and mother-infant interaction quality on childhood atopic dermatitis (rash) at 18 months
Nela Cosic, Henry Ntanda, Gerald Giesbrecht, Anita Kozyrskyj, Nicole Letourneau
A46 Examining the immunological mechanisms associated with cow’s milk allergy
Bassel Dawod, Jean Marshall
A47 Tryptase levels in children presenting with anaphylaxis to the Montréal Children’s Hospital
Sarah De Schryver, Michelle Halbrich, Ann Clarke, Sebastian La Vieille, Harley Eisman, Reza Alizadehfar, Lawrence Joseph, Judy Morris, Moshe Ben-Shoshan
A48 Secondhand tobacco smoke exposure in infancy and the development of food hypersensitivity from childhood to adolescence
Laura Y. Feldman, Jesse D. Thacher, Inger Kull, Erik Melén, Göran Pershagen, Magnus Wickman, Jennifer L. P. Protudjer, Anna Bergström
A49 Combined exposure to diesel exhaust and allergen enhances allergic inflammation in the bronchial submucosa of atopic subjects
Ali Hosseini, Tillie L. Hackett, Jeremy Hirota, Kelly McNagny, Susan Wilson, Chris Carlsten
A50 Comparison of skin-prick test measurements by an automated system against the manual method
Saiful Huq, Rishma Chooniedass, Brenda Gerwing, Henry Huang, Diana Lefebvre, Allan Becker
A51 The accurate identification and quantification of urinary biomarkers of asthma and COPD through the use of novel DIL- LC-MS/MS methods
Mona M. Khamis, Hanan Awad, Kevin Allen, Darryl J. Adamko, Anas El-Aneed
A52 Systemic immune pathways associated with the mechanism of Cat-Synthetic Peptide Immuno-Regulatory Epitopes, a novel immunotherapy, in whole blood of cat-allergic people
Young Woong Kim, Daniel R. Gliddon, Casey P. Shannon, Amrit Singh, Pascal L. C. Hickey, Anne K. Ellis, Helen Neighbour, Mark Larche, Scott J. Tebbutt
A53 Reducing the health disparities: online support for children with asthma and allergies from low-income families
Erika Ladouceur, Miriam Stewart, Josh Evans, Jeff Masuda, Nicole Letourneau, Teresa To, Malcolm King
A54 Epigenetic association of PSORS1C1 and asthma in the Saguenay-Lac-Saint-Jean asthma study
Miriam Larouche, Liming Liang, Catherine Laprise
A55 IL-33 induces cytokine and chemokine production in human mast cells
Stephanie A. Legere, Ian D. Haidl, Jean-Francois Legaré, Jean S. Marshall
A56 Reference ranges for lung clearance index from infancy to adolescence for Canadian population
Zihang Lu, Malcolm Sears, Theo J. Moraes, Felix Ratjen, Per Gustafsson, Wendy Lou, Padmaja Subbarao
A57 Kingston Allergy Birth Cohort: cohort profile and mother/child characteristics to age 2
Michelle L. North, Elizabeth Lee, Vanessa Omana, Jenny Thiele, Jeff Brook, Anne K. Ellis
A58 Cow’s milk protein specific IgE, IgA and IgG4 as a predictor of outcome in oral immunotherapy
Tanvir Rahman, Duncan Lejtenyi, Sarah De Schryver, Ryan Fiter, Ciriaco Piccirillo, Moshe Ben-Shoshan, Bruce Mazer
A59 Age of peanut introduction and development of reactions and sensitization to peanut
Elinor Simons, Allan B. Becker, Rishma Chooniedass, Kyla Hildebrand, Edmond S. Chan, Stuart Turvey, Padmaja Subbarao, Malcolm Sears
A60 Multi-omic blood biomarker signatures of the late phase asthmatic response
Amrit Singh, Casey P. Shannon, Young Woong Kim, Mari DeMarco, Kim-Anh Le Cao, Gail M. Gauvreau, J. Mark FitzGerald, Louis-Philippe Boulet, Paul M. O’Byrne, Scott J. Tebbutt
A61 Early life gut microbial alterations in children diagnosed with asthma by three years of age
Leah T. Stiemsma, Marie-Claire Arrieta, Jasmine Cheng, Pedro A. Dimitriu, Lisa Thorson, Sophie Yurist, Boris Kuzeljevic, Diana L. Lefebvre, Padmaja Subbarao, Piush Mandhane, Allan Becker, Malcolm R. Sears, Kelly M. McNagny, Tobias Kollmann, the CHILD Study Investigators, William W. Mohn, B. Brett Finlay, Stuart E. Turvey
A62 The relationship between food sensitization and atopic dermatitis at age 1 year in a Canadian birth cohort
Maxwell M. Tran, Diana L. Lefebvre, Chinthanie F. Ramasundarahettige, Allan B. Becker, Wei Hao Dai, Padmaja Subbarao, Piush J. Mandhane, Stuart E. Turvey, Malcolm R. Sears
A63 Allergen inhalation enhances Toll-like receptor-induced thymic stromal lymphopoietin receptor expression by hematopoietic progenitor cells in mild asthmatics
Damian Tworek, Delia Heroux, Seamus N. O’Byrne, Paul M. O’Byrne, Judah A. Denburg
A64 The Allergic Rhinitis Clinical Investigator Collaborative – replicated eosinophilia on repeated cumulative allergen challenges in nasal lavage samples
Laura Walsh, Mena Soliman, Jenny Thiele, Lisa M. Steacy, Daniel E. Adams, Anne K. Ellis
A65 The CHILD Study: optimizing subject retention in pediatric longitudinal cohort research
Linda Warner, Mary Ann Mauro, Robby Mamonluk, Stuart E. Turvey
A66 Differential expression of C3a and C5a in allergic asthma
ChenXi Yang, Amrit Singh, Casey P. Shannon, Young Woong Kim, Ed M. Conway, Scott J. Tebbut
The sleep-deprived human brain
How does a lack of sleep affect our brains? In contrast to the benefits of sleep, frameworks exploring the impact of sleep loss are relatively lacking. Importantly, the effects of sleep deprivation (SD) do not simply reflect the absence of sleep and the benefits attributed to it; rather, they reflect the consequences of several additional factors, including extended wakefulness. With a focus on neuroimaging studies, we review the consequences of SD on attention and working memory, positive and negative emotion, and hippocampal learning. We explore how this evidence informs our mechanistic understanding of the known changes in cognition and emotion associated with SD, and the insights it provides regarding clinical conditions associated with sleep disruption