Childrens and Womens Health Center

Vancouver, Canada

Childrens and Womens Health Center

Vancouver, Canada
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Alfadhel M.,Childrens and Womens Health Center | Lillquist Y.P.,Childrens and Womens Health Center | Waters P.J.,Childrens and Womens Health Center | Sinclair G.,Childrens and Womens Health Center | And 4 more authors.
American Journal of Medical Genetics, Part A | Year: 2011

We describe respiratory chain complex IV deficiency (cytochrome c oxidase deficiency) in a female infant with a neonatal rapidly progressive fatal course characterized by microcephaly, encephalopathy, persistent lactic acidosis, and hypertrophic cardiomyopathy. Postmortem cardiac muscle study showed marked complex IV deficiency. In contrast, complex IV activity was only slightly decreased in the skeletal muscle. Subsequent molecular investigations showed compound heterozygosity for two known pathogenic mutations in the COX15 gene. We compare the findings in our patient to those of the three previously reported cases. © 2011 Wiley-Liss, Inc.


Mataseje L.F.,Public Health Agency of Canada | Bryce E.,Vancouver General Hospital | Roscoe D.,Vancouver General Hospital | Boyd D.A.,Public Health Agency of Canada | And 39 more authors.
Journal of Antimicrobial Chemotherapy | Year: 2012

Objectives: To investigate the occurrence and molecular mechanisms associated with carbapenemases in carbapenem-resistant Gram-negative isolates from Canadian cases. Methods: Twenty hospital sites across Canada submitted isolates for a 1 year period starting 1 September 2009. All Enterobacteriaceae with MICs ≥2 mg/L and Acinetobacter baumannii and Pseudomonas aeruginosa with MICs ≥16 mg/L of carbapenems were submitted to the National Microbiology Laboratory (NML) where carbapenem MICs were confirmed by Etest and isolates were characterized by PCR for carbapenemase genes, antimicrobial susceptibilities, PFGE and plasmid isolation. Results: A total of 444 isolates (298 P. aeruginosa, 134 Enterobacteriaceae and 12 A. baumannii) were submitted to the NML of which 274 (61.7%; 206 P. aeruginosa, 59 Enterobacteriaceae and 9 A. baumannii) met the inclusion criteria as determined by Etest. Carbapenemase genes were identified in 30 isolates: blaGES-5 (n = 3; P. aeruginosa), blaKPC-3 (n = 7; Enterobacteriaceae), blaNDM-1 (n = 2; Enterobacteriaceae), blaVIM-2 and blaVIM-4 (n = 8; P. aeruginosa) blaSME-2 (n = 1; Enterobacteriaceae) and blaOXA-23 (n = 9; A. baumannii). PFGE identified a cluster in each of Enterobacteriaceae, P. aeruginosa and A. baumannii corresponding to isolates harbouring carbapenemase genes. Three KPC plasmid patterns (IncN and FllA) were identified where indistinguishable plasmid patterns were identified in unrelated clinical isolates. Conclusions: Carbapenemases were rare at the time of this study. Dissemination of carbapenemases was due to both dominant clones and common plasmid backbones. © Crown copyright 2012.


Simor A.E.,Sunnybrook Health science Center | Gilbert N.L.,Public Health Agency of Canada | Mulvay M.R.,Public Health Agency of Canada | Bryce E.,Vancouver General Hospital | And 36 more authors.
Infection Control and Hospital Epidemiology | Year: 2010

OBJECTIVE. To determine the incidence and describe the changing epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) colonization or infection in Canadian hospitals from 1995-2007. SETTING. Forty-eight hospitals participating in the Canadian Nosocomial Infection Surveillance Program. DESIGN. Prospective, laboratory-based surveillance for incident cases of MRSA colonization or infection among hospitalized patients. METHODS. Clinical and epidemiologic data were obtained by review of hospital records. Standard criteria were used to determine whether MRSA colonization or infection was present and whether the MRSA strain was healthcare associated or community associated. A representative subset of isolates was characterized by use of pulsed-field gel electrophoresis and staphylococcal cassette chromosome (SCC) mec typing. RESULTS. From 1995 to 2007, a total of 37, 169 hospitalized patients were newly identified as either infected or colonized with MRSA, and the overall incidence of both MRSA colonization and MRSA infection increased from 0.65 to 11.04 cases per 10, 000 patient-days (P<.001). Of these 37, 169 patients, 11, 828 (32%) had an MRSA infection, and infection rate increased from 0.36 to 3.43 cases per 10, 000 patient-days. The proportion of community-associated MRSA strains increased from 6% to 23% (P<.001). The most common genotype (47% of isolates) was CMRSA-2 (USA100/800); in 2007, CMRSA-10 (USA300) was the second most common strain (27% of isolates), associated with SCCmec type IV. Patients with CMRSA-10 were predominantly from western Canada and were more likely to be children (odds ratio [OR], 10.0 [95% confidence interval {CI}, 7.4-13.4]) and to have infection (OR, 2.3 [95% CI, 1.9-2.7]), especially skin and/or soft tissue infection (OR, 5.9 [95% CI, 5.0-6.9]). CONCLUSIONS. The overall incidence of both MRSA colonization and MRSA infection increased 17-fold in Canadian hospitals from 1995 to 2007. There has also been a dramatic increase in cases of community-associated MRSA infection due to the CMRSA-10 (USA300) clone. Continued surveillance is needed to monitor the ongoing evolution of MRSA colonization or infection in Canada and globally. © 2010 by The Society for Healthcare Epidemiology of America.


McCracken M.,Public Health Agency of Canada | Wong A.,Royal University | Mitchell R.,Public Health Agency of Canada | Gravel D.,Public Health Agency of Canada | And 49 more authors.
Journal of Antimicrobial Chemotherapy | Year: 2013

Objectives: Vancomycin-resistant enterococci (VRE) can be associated with serious bacteraemia. The focus of this study was to characterize the molecular epidemiology of VRE from bacteraemia cases that were isolated from 1999 to 2009 as part of Canadian Nosocomial Infection Surveillance Program (CNISP) surveillance activities. Methods: From 1999 to 2009, enterococci were collected from across Canada in accordance with the CNISP VRE surveillance protocol. MICs were determined using broth microdilution. PCR was used to identify vanA, B, C, D, E, G and L genes. Genetic relatedness was examined using multilocus sequence typing (MLST). Results: A total of 128 cases of bacteraemia were reported to CNISP from 1999 to 2009. In 2007, a significant increase in bacteraemia rates was observed in western and central Canada. Eighty-one of the 128 bacteraemia isolates were received for further characterization and were identified as Enterococcus faecium. The majority of isolates were from western Canada (60.5%), followed by central (37.0%) and eastern (2.5%) Canada. Susceptibilities were as follows: daptomycin, linezolid, tigecycline and chloramphenicol, 100%; quinupristin/dalfopristin, 96.3%; high-level gentamicin, 71.6%; tetracycline, 50.6%; high-level streptomycin, 44.4%; rifampicin, 21.0%; nitrofurantoin, 11.1%; clindamycin, 8.6%; ciprofloxacin, levofloxacin and moxifloxacin, 1.2%; and ampicillin, 0.0%. vanA contributed to vancomycin resistance in 90.1% of isolates and vanB in 9.9%. A total of 17 sequence types (STs) were observed. Beginning in 2006 there was a shift in ST from ST16, ST17, ST154 and ST80 to ST18, ST412, ST203 and ST584. Conclusions: The increase in bacteraemia observed since 2007 in western and central Canada appears to coincide with the shift of MLST STs. All VRE isolates remained susceptible to daptomycin, linezolid, chloramphenicol and tigecycline. © Crown copyright 2013.


Boyd D.,Public Health Agency of Canada | Taylor G.,University of Alberta | Fuller J.,University of Alberta | Bryce E.,Vancouver General Hospital | And 13 more authors.
Microbial Drug Resistance | Year: 2015

The usefulness of carbapenems for gram-negative infections is becoming compromised by organisms harboring carbapenemases, enzymes which can hydrolyze the drug. Currently KPC (class A), NDM (class B), and OXA-48 types (class D) are the most globally widespread carbapenemases. However, among the GES-type class A extended-spectrum β-lactamases (ESBLs) there are variants that hydrolyze carbapenems, with blaGES-5 being the most common. Two Escherichia coli and two Serratia marcescens harboring blaGES-5 on plasmids were isolated by the Canadian Nosocomial Infection Surveillance Program (CNISP) from four different patients in a single hospital over a 2-year period. Complete sequencing of the blaGES-5 plasmids indicated that all four had nearly identical backbones consisting of genes for replication, partitioning, and stability, but contained variant accessory regions consisting of mobile elements and antimicrobial resistance genes. The plasmids were of a novel replicon type, but belonged to the MOBQ1 group based on relaxase sequences, and appeared to be mobilizable, but not self-transmissible. Considering the time periods of bacterial isolation, it would appear the blaGES-5 plasmid has persisted in an environmental niche for at least 2 years in the hospital. This has implications for infection control and clinical care when it is transferred to clinically relevant gram-negative organisms. © Copyright 2015, Mary Ann Liebert, Inc.


Bond D.J.,University of British Columbia | Hadjipavlou G.,University of British Columbia | Lam R.W.,University of British Columbia | McIntyre R.S.,University of Toronto | And 3 more authors.
Annals of Clinical Psychiatry | Year: 2012

BACKGROUND: Patients with bipolar disorder (BD) and major depressive disorder (MDD) experience adult attention-deficit/hyperactivity disorder (ADHD) at rates substantially greater than the general population. Nonetheless, ADHD frequently goes untreated in this population. METHODS: We reviewed the literature regarding the management of adult ADHD in patients with mood disorders. Because a limited number of studies have been conducted in adults, our treatment recommendations also are partly informed by research in children and adolescents with BD+ADHD or MDD+ADHD, adults with ADHD, and our clinical experience. RESULTS: In individuals with mood disorders, ADHD is best diagnosed when typical symptoms persist during periods of sustained euthymia. Individuals with BD+ADHD, particularly those with bipolar I disorder (BD I), are at risk for mood destabilization with many ADHD treatments, and should be prescribed mood-stabilizing medications before initiating ADHD therapies. Bupropion is a reasonable first-line treatment for BD+ADHD, while mixed amphetamine salts and methylphenidate also may be considered in patients determined to be at low risk for manic switch. Modafinil and cognitive-behavioral therapy (CBT) are second-line choices. In patients with MDD+ADHD and moderate to severe depression, MDD should be the treatment priority, whereas in mildly depressed or euthymic patients the order may be reversed. First-line treatments for MDD+ADHD include bupropion, an antidepressant plus a long-acting stimulant, or an antidepressant plus CBT. Desipramine, nortriptyline, and venlafaxine are second-line options. CONCLUSIONS: Clinicians should be vigilant in screening for comorbid ADHD in mood disorder patients. ADHD symptoms can respond to appropriately chosen treatments.


Jackson H.A.,University of British Columbia | Mcintosh S.,University of British Columbia | Whittome B.,University of British Columbia | Asuri S.,University of British Columbia | And 4 more authors.
Clinical Genetics | Year: 2014

Long QT syndrome (LQTS), a rare congenital cardiac condition associated with life-threatening ventricular arrhythmias is characterized by a prolonged QT interval on electrocardiograph corrected for heart rate [corrected QT (QTc)]. LQTS has been historically categorized into the autosomal dominant Romano-Ward syndrome (RWS) and the autosomal recessive Jervell and Lange-Nielsen syndrome (JLNS). JLNS is associated with prelingual sensorineural deafness. Both types of LQTS can be caused by mutations in channel genes (e.g. KCNQ1) responsible for potassium homeostasis in cardiac myocytes and cochlea. Autosomal dominant mutations often cause the RWS phenotype and homozygous or compound heterozygous mutations contribute to JLNS. Two First Nations communities in northern British Columbia are affected disproportionately with LQTS largely due to the V205M mutation in KCNQ1, however, the pathology and phenotypic expression for those V205M homozygous has been unknown. Here, we show that four V205M homozygous individuals have a significantly higher 'peak' QTc, and a more severe cardiac phenotype compared with 41 V205M heterozygous carriers and 57 first to third degree relatives without mutations. Given the lack of prelingual deafness the homozygous V205M LQTS patients present with a phenotype more typical of RWS than JLNS. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.


Hodgkins P.,Health Economics Outcomes Research HEOR | Lloyd A.,Patient Reported Outcomes | Erder M.H.,Health Economics Outcomes Research HEOR | Setyawan J.,Health Economics Outcomes Research HEOR | And 3 more authors.
CNS Spectrums | Year: 2016

Objective: Defining minimal important difference (MID) is critical to interpreting patient-reported outcomes data and treatment efficacy in clinical trials. This study estimates the MID for the Weiss Functional Impairment Rating Scale–Parent Report (WFIRS-P) and the Child Health and Illness Profile–Parent Report (CHIP-CE-PRF76) among parents of young people with attention-deficit/hyperactivity disorder (ADHD) in the UK. Methods: Parents of children (6–12 years; n=100) and adolescents (13–17 years; n=117) with ADHD completed a socio-demographic form, the CHIP-CE-PRF76, the WFIRS-P, and the Pediatric Quality of Life scale at baseline and 4 weeks later. At follow-up, a subset of parents completed anchor questions measuring change in the child/adolescent from baseline. MIDs were estimated using anchor-based and distribution-based methods, and separately for children and adolescents. Results: The MID estimates for overall change in the WFIRS-P total score ranged from 11.31 (standard error of measurement) to 13.47 (anchor) for the total sample. The range of MID estimates for the CHIP-CE-PRF76 varied by domain: 6.80–7.41 (satisfaction), 6.18–7.34 (comfort), 5.60–6.72 (resilience), 6.06–7.57 (risk avoidance), and 4.00–5.63 (achievement) for the total sample. Overall, MID estimates for WFIRS-P MID and CHIP-CE-PRF76 were slightly higher for adolescents than for children. Conclusion: This study estimated MIDs for these instruments using several methods. The observed convergence of the MID estimates increases confidence in their reliability and could assist clinicians and decision makers in deriving meaningful interpretations of observed changes in the WFIRS-P and CHIP-CE in clinical trials and practice. © Cambridge University Press 2016


PubMed | Childrens and Womens Health Center
Type: Journal Article | Journal: Journal of attention disorders | Year: 2012

To examine factor structures of Diagnostic and Statistical Manual of Mental Disorders (4th ed.) symptoms of ADHD in adults.Two sets of models were tested: (a) models with inattention and hyperactivity/impulsivity as separate but correlated latent constructs and (b) hierarchical general factor models with a general factor for all symptoms and separate specific factors for inattention and hyperactivity/impulsivity. Participants were 751 adults with ADHD. Two models with correlated factors and two general factor models of ADHD symptoms were tested.The general factor model provided a better fit of the data than the correlated models. The general factor model with one general and three (inattention, motoric, and verbal hyperactivity/impulsivity) specific factors best accounted for the adults symptoms.These results suggest a unitary component to ADHD symptoms as well as dimensional specific factors. The replication of a general factor in adults suggests continuity of symptom presentation from childhood into adulthood. Clinical implications are discussed.


PubMed | Childrens and Womens Health Center
Type: Case Reports | Journal: American journal of medical genetics. Part A | Year: 2011

We describe respiratory chain complex IV deficiency (cytochrome c oxidase deficiency) in a female infant with a neonatal rapidly progressive fatal course characterized by microcephaly, encephalopathy, persistent lactic acidosis, and hypertrophic cardiomyopathy. Postmortem cardiac muscle study showed marked complex IV deficiency. In contrast, complex IV activity was only slightly decreased in the skeletal muscle. Subsequent molecular investigations showed compound heterozygosity for two known pathogenic mutations in the COX15 gene. We compare the findings in our patient to those of the three previously reported cases.

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