Child and Family Research Institute of British Columbia

Vancouver, Canada

Child and Family Research Institute of British Columbia

Vancouver, Canada
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Etminan M.,Child and Family Research Institute of British Columbia | Etminan M.,University of British Columbia | Forooghian F.,University of British Columbia | Brophy J.M.,McGill University | And 2 more authors.
JAMA - Journal of the American Medical Association | Year: 2012

Context: Fluoroquinolones are commonly prescribed classes of antibiotics. Despite numerous case reports of ocular toxicity, a pharmacoepidemiological study of their ocular safety, particularly retinal detachment, has not been performed. Objective: To examine the association between use of oral fluoroquinolones and the risk of developing a retinal detachment. Design, Setting, and Patients: Nested case-control study of a cohort of patients in British Columbia, Canada, who had visited an ophthalmologist between January 2000 and December 2007. Retinal detachment cases were defined as a procedure code for retinal repair surgery within 14 days of a physician service code. Ten controls were selected for each case using risk-set sampling, matching on age and the month and year of cohort entry. Main Outcome Measure: The association between retinal detachment and current, recent, or past use of an oral fluoroquinolone. Results: From a cohort of 989 591 patients, 4384 cases of retinal detachment and 43 840 controls were identified. Current use of fluoroquinolones was associated with a higher risk of developing a retinal detachment (3.3% of cases vs 0.6% of controls; adjusted rate ratio [ARR], 4.50 [95% CI, 3.56-5.70]). Neither recent use (0.3% of cases vs 0.2% of controls; ARR, 0.92 [95% CI, 0.45-1.87]) nor past use (6.6% of cases vs 6.1% of controls; ARR, 1.03 [95% CI, 0.89-1.19]) was associated with a retinal detachment. The absolute increase in the risk of a retinal detachment was 4 per 10 000 person-years (number needed to harm=2500 computed for any use of fluoroquinolones). There was no evidence of an association between development of a retinal detachment and β-lactam antibiotics (ARR, 0.74 [95% CI, 0.35-1.57]) or short-acting β-agonists (ARR, 0.95 [95% CI, 0.68-1.33]). Conclusion: Patients taking oral fluoroquinolones were at a higher risk of developing a retinal detachment compared with nonusers, although the absolute risk for this condition was small. ©2012 American Medical Association. All rights reserved.


Syme R.,University of Calgary | Carleton B.,Child and Family Research Institute of British Columbia | Leyens L.,Maastricht University | Richer E.,CIHR Institute of Genetics
Public Health Genomics | Year: 2015

There is currently a rapid evolution of clinical practices based on the introduction of patient stratification and molecular diagnosis that is likely to improve health outcomes. Building on a strong research base, complemented by strong support from clinicians and health authorities, the oncology field is at the forefront of this evolution. Yet, clinical research is still facing many challenges that need to be addressed in order to conduct necessary studies and effectively translate medical breakthroughs based on personalized medicine into standards of care. Leveraging its universal health care system and on resources developed to support oncology clinical research, Canada is well positioned to join the international efforts deployed to address these challenges. Available resources include a broad range of structures and funding mechanisms, ranging from direct clinical trial support to post-marketing surveillance. Here, we propose a clinical model for the introduction of innovation for precision medicine in oncology that starts with patients' and clinicians' unmet needs to initiate a cycle of discovery, validation, translation and sustainability development. © 2015 S. Karger AG, Basel. All rights reserved.


Huusko J.M.,University of Oulu | Mahlman M.,University of Oulu | Karjalainen M.K.,University of Oulu | Kaukola T.,University of Oulu | And 9 more authors.
Pediatric Pulmonology | Year: 2015

Bronchopulmonary dysplasia (BPD) is a chronic inflammatory lung disease that affects infants born preterm. Family studies indicate that BPD has a significant genetic component. Rationale: We assessed the gene encoding Kit ligand ( KITLG) as a candidate for genetic predisposition to moderate-to-severe BPD (controls were infants with no or mild BPD). Study design: Eight KITLG-tagging single nucleotide polymorphisms (SNPs) were analyzed in cohorts of very preterm infants originating from northern Finland (56 cases and 197 controls), southern Finland (n = 59 + 52), and Canada (n = 58 + 68). Additional replication populations included infants born in Finland (n = 41 + 241) and Hungary (n = 29 + 40). All infants were of European origin. Results were controlled for risk factors of BPD. Kit ligand concentration in umbilical cord blood, collected from very preterm infants (n = 120), was studied. Results: Six SNPs of KITLG and a haplotype including all eight genotyped SNPs were associated with moderate-to-severe BPD in the northern Finnish population. When all the populations were combined, SNP rs11104948 was significantly associated with BPD. Kit ligand concentration in umbilical cord blood of infants born very preterm was an independent risk factor of BPD. Conclusions: We show that KITLG polymorphisms are associated with susceptibility to moderate-to-severe BPD. In addition, higher Kit ligand concentrations were observed in infants that subsequently developed BPD. These results support the possibility that KITLG gene is involved in predisposition to BPD. © 2014 Wiley Periodicals, Inc.


Etminan M.,University of British Columbia | Etminan M.,Child and Family Research Institute of British Columbia | Brophy J.M.,McGill University | Samii A.,University of Washington
Neurology | Year: 2014

Objective: To quantify the risk of peripheral neuropathy (PN) with oral fluoroquinolone (FQ) use. Methods: We conducted a case-control study within a cohort of men aged 45 to 80 years in the United States followed from 2001 to 2011. Cases were defined as those with the first physician visit diagnosis of PN, polyneuropathy, or drug-induced polyneuropathy. Four controls were matched to each case by age, follow-up, and calendar time using density-based sampling. As a sensitivity analysis, we also quantified the risk of PN with finasteride use, a drug that is not expected to increase the risk of PN. Rate ratios (RRs) for current users of FQs were computed using conditional logistic regression, which was adjusted for chronic renal failure, chronic liver disease, hypothyroidism, postherpetic neuralgia, and the use of nitrofurantoin and metronidazole. Results: We identified 6,226 cases and 24,904 controls. Current users of FQs were at a higher risk of developing PN (RR = 1.83, 95% confidence interval [CI] 1.49-2.27). Current new users had the highest risk (RR = 2.07, 95% CI 1.56-2.74). No risk was observed for current users of finasteride (RR = 1.21, 95% CI 0.97-1.51). Conclusions: Current users, especially new users of FQs, are at a higher risk of developing PN. Despite the increase in the use of FQs, clinicians should weigh the benefits against the risk of adverse events when prescribing these drugs to their patients. © 2014 American Academy of Neurology.


Forooghian F.,University of British Columbia | Maberley D.,University of British Columbia | Albiani D.A.,University of British Columbia | Kirker A.W.,University of British Columbia | And 2 more authors.
Ocular Immunology and Inflammation | Year: 2013

Objective: To determine the risk of uveitis associated with the use of oral fluoroquinolones. Methods: Nested case-control study of all patients who visited an ophthalmologist in British Columbia, Canada, between 2000 and 2007, as captured in the British Columbia Health Linked Database. Results: A total 3383 incident cases of uveitis and 33,830 corresponding controls were identified. Among patients who had used oral fluoroquinolones within the past 30 days, the adjusted relative risk of uveitis was 3.53 (95% CI, 2.84-4.39). However, the relative risk of uveitis among patients taking oral macrolides and beta-lactams was also significantly elevated. Conclusions: Our data do not provide convincing evidence of an association between fluoroquinolones and uveitis, as this study found an association between several classes of antibiotics and uveitis. It is possible that the systemic processes for which these antibiotics are being prescribed are in fact the inciting factors for the uveitis. © 2013 Informa Healthcare USA, Inc. All rights reserved: reproduction in whole or part not permitted.


Lavoie P.M.,Child and Family Research Institute of British Columbia | Lavoie P.M.,University of British Columbia | Ladd M.,Child and Family Research Institute of British Columbia | Hirschfeld A.F.,Child and Family Research Institute of British Columbia | And 8 more authors.
PLoS ONE | Year: 2012

Bronchopulmonary dysplasia (BPD) is a common chronic lung disease and major risk factor for severe respiratory syncytial virus (RSV) infection among preterm infants. The Toll-like receptor 4 (TLR4) is involved in oxidative injury responses in the lungs. Two non-synonymous single nucleotide polymorphisms in the TLR4 gene have been associated with RSV infection in children. However, it is unclear to what extent this association is confounded by BPD or prematurity. In this study, we analyzed two population-based cohorts of preterm infants at risk for BPD as well as ethnicity-matched infants born at term, to test whether the TLR4 polymorphisms Asp299Gly (rs4986790) and Thr399Ile (rs4986791) are independently associated with BPD or premature birth. In a Canadian cohort (n = 269) composed of a majority of Caucasian preterm infants (BPD incidence of 38%), the TLR4-299 heterozygous genotype was significantly under-represented in infants without BPD (1.6% of infants versus 12% in infants with severe BPD) after adjusting for twins, ethnicity, gestational age, birth weight and gender (p = 0.014). This association was not replicated in a Finnish cohort (n = 434) of premature singletons or first-born siblings of Caucasian descent, although the incidence of BPD was substantially lower in this latter population (15%). We did not detect a significant association (>2-fold) between TLR4 genotypes and prematurity (p>0.05). We conclude that these TLR4 genotypes may have, at best, a modest influence on BPD severity in some populations of high-risk preterm infants. Further studies are warranted to clarify how clinical heterogeneity may impact genetic susceptibility to BPD. © 2012 Lavoie et al.


Novak E.M.,Child and Family Research Institute of British Columbia | Keller B.O.,Child and Family Research Institute of British Columbia | Innis S.M.,Child and Family Research Institute of British Columbia
Nestle Nutrition Workshop Series: Pediatric Program | Year: 2011

Understanding the importance of dietary fat has grown beyond energy metabolism to recognition of the complex roles of fatty acids, particularly the ω-6 and ω-3 fatty acids in membrane lipids, inter- and intracellular communication and in regulating gene expression. The ω-6 and ω-3 fatty acids accumulated in developing tissues depend on the fatty acids transported across the placenta and secreted in breast milk. These in turn are dependent on maternal fatty acid intakes, which have changed dramatically in the past century with current western diets high in ω-6 linoleic acid and low in ω-3 fatty acids. High intakes of ω-6 fatty acid and low intakes of ω-3 fatty acids compromise long-chain ω-3 fatty acid accumulation in tissues, and this is avoided by dietary docosahexaenoic acid. In addition to the well-known roles in neural development, newer studies are beginning to question the importance of ω-3 fatty acids as a contributor of metabolic development in other organs, with possible implications for the development of feeding behavior and integration of the nutrient energy supply. Copyright © 2011 S. Karger AG, Basel.


Innis S.M.,Child and Family Research Institute of British Columbia
Maternal and Child Nutrition | Year: 2011

Understanding of the importance of dietary fatty acids has grown beyond a simple source of energy to complex roles in regulating gene expression and cell and intracellular communication. This is important because the metabolic and neuroendocrine environment of the fetus and infant plays a key role in guiding the set point of neural receptors that regulate energy homeostasis and expression of genes that control energy storage and oxidation. Early deviations in these pathways have the potential to lead to lasting adaptations, termed metabolic programming, which may combine to increase the risk of metabolic syndrome in later life. The quality of fatty acids in human diets has undergone major changes in the last 50 years, characterized by an increase in ω-6 and decrease in ω-3 fatty acids. Evidence is accumulating to support the concept that the maternal intake of ω-6 and ω-3 fatty acids in gestation and lactation, possibly involving both excess ω-6 and inadequate ω-3 fatty acids, can impact the developing infant tissue lipids and neuroendocrine and metabolic pathways relevant to metabolic programming. Further work is needed to understand the needs for different ω-6 and ω-3 fatty acids during fetal and infant life, and their roles with respect to development of energy homeostasis and metabolism. © 2011 Blackwell Publishing Ltd.


PubMed | Child and Family Research Institute of British Columbia
Type: Journal Article | Journal: JAMA | Year: 2012

Fluoroquinolones are commonly prescribed classes of antibiotics. Despite numerous case reports of ocular toxicity, a pharmacoepidemiological study of their ocular safety, particularly retinal detachment, has not been performed.To examine the association between use of oral fluoroquinolones and the risk of developing a retinal detachment.Nested case-control study of a cohort of patients in British Columbia, Canada, who had visited an ophthalmologist between January 2000 and December 2007. Retinal detachment cases were defined as a procedure code for retinal repair surgery within 14 days of a physician service code. Ten controls were selected for each case using risk-set sampling, matching on age and the month and year of cohort entry.The association between retinal detachment and current, recent, or past use of an oral fluoroquinolone.From a cohort of 989,591 patients, 4384 cases of retinal detachment and 43,840 controls were identified. Current use of fluoroquinolones was associated with a higher risk of developing a retinal detachment (3.3% of cases vs 0.6% of controls; adjusted rate ratio [ARR], 4.50 [95% CI, 3.56-5.70]). Neither recent use (0.3% of cases vs 0.2% of controls; ARR, 0.92 [95% CI, 0.45-1.87]) nor past use (6.6% of cases vs 6.1% of controls; ARR, 1.03 [95% CI, 0.89-1.19]) was associated with a retinal detachment. The absolute increase in the risk of a retinal detachment was 4 per 10,000 person-years (number needed to harm = 2500 computed for any use of fluoroquinolones). There was no evidence of an association between development of a retinal detachment and -lactam antibiotics (ARR, 0.74 [95% CI, 0.35-1.57]) or short-acting -agonists (ARR, 0.95 [95% CI, 0.68-1.33]).Patients taking oral fluoroquinolones were at a higher risk of developing a retinal detachment compared with nonusers, although the absolute risk for this condition was small.


PubMed | Child and Family Research Institute of British Columbia
Type: | Journal: Nestle Nutrition workshop series. Paediatric programme | Year: 2011

Understanding the importance of dietary fat has grown beyond energy metabolism to recognition of the complex roles of fatty acids, particularly the -6 and -3 fatty acids in membrane lipids, inter- and intracellular communication and in regulating gene expression. The -6 and -3 fatty acids accumulated in developing tissues depend on the fatty acids transported across the placenta and secreted in breast milk. These in turn are dependent on maternal fatty acid intakes, which have changed dramatically in the past century with current western diets high in -6 linoleic acid and low in -3 fatty acids. High intakes of -6 fatty acid and low intakes of -3 fatty acids compromise long-chain -3 fatty acid accumulation in tissues, and this is avoided by dietary docosahexaenoic acid. In addition to the well-known roles in neural development, newer studies are beginning to question the importance of -3 fatty acids as a contributor of metabolic development in other organs, with possible implications for the development of feeding behavior and integration of the nutrient energy supply.

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