Trauma is a leading cause of morbidity, potential years of life lost and health care expenditure in Canada and around the world. Trauma systems have been established across North America to provide comprehensive injury care and to lead injury control efforts. We sought to describe the current status of trauma systems in Canada and Canadians' access to acute, multidisciplinary trauma care.
A national survey was used to identify the locations and capabilities of adult trauma centers across Canada and to identify the catchment populations they serve. Geographic information science methods were used to map the locations of Level I and Level II trauma centers and to define 1-hour road travel times around each trauma center. Data from the 2006 Canadian Census were used to estimate populations within and outside 1-hour access to definitive trauma care.
In Canada, 32 Level I and Level II trauma centers provide definitive trauma care and coordinate the efforts of their surrounding trauma systems. Most Canadians (77.5%) reside within 1-hour road travel catchments of Level I or Level II centers. However, marked geographic disparities in access persist. Of the 22.5% of Canadians who live more than an hour away from a Level I or Level II trauma centers, all are in rural and remote regions.
Access to high quality acute trauma care is well established across parts of Canada but a clear urban/rural divide persists. Regional efforts to improve short- and long-term outcomes after severe trauma should focus on the optimization of access to pre-hospital care and acute trauma care in rural communities using locally relevant strategies or novel care delivery options.
Ethnicity can confound results in pharmacogenomic studies. Allele frequencies of loci that influence drug metabolism can vary substantially between different ethnicities and underlying ancestral genetic differences can lead to spurious findings in pharmacogenomic association studies. We evaluated the application of principal component analysis (PCA) in a pharmacogenomic study in Canada to detect and correct for genetic ancestry differences using genotype data from 2094 loci in 220 key drug biotransformation genes. Using 89 Coriell worldwide reference samples, we observed a strong correlation between principal component values and geographic origin. We further applied PCA to accurately infer the genetic ancestry in our ethnically diverse Canadian cohort of 524 patients from the GATC study of severe adverse drug reactions. We show that PCA can be successfully applied in pharmacogenomic studies using a limited set of markers to detect underlying differences in genetic ancestry thereby maximizing power and minimizing false-positive findings.
Cerebellar hypoplasia is a rare malformation caused by a variety of etiologies. It usually manifests clinically as non-progressive cerebellar ataxia with or without mental retardation. We further characterize a syndrome of autosomal recessive cerebellar hypoplasia in the Hutterite population, referred to as dysequilibrium syndrome (DES). We reviewed 12 patients (eight females, four males; age range 4 to 33 y) with this syndrome. Patients were examined and underwent a standard set of investigations to characterize better the clinical features, natural history, and neuroimaging of this syndrome. DES is an autosomal recessive disorder with distinct clinical features including global developmental delay, late ambulation (after age 6 y), truncal ataxia, and a static clinical course. Neuroimaging is characterized by hypoplasia of the inferior portion of the cerebellar hemispheres and vermis, and mild simplification of cortical gyri.
Bilateral anterior temporomandibular joint dislocation is very rare, with only 2 reported cases published. In the present report, we describe a healthy 25-year-old man from Haida Gwaii, in British Columbia, Canada, who was transferred to our tertiary trauma center with life-threatening complications of a bilateral anterior temporomandibular joint dislocation with locked mandibular impaction.
Adverse drug reactions (ADRs) rank as one of the top 10 leading causes of death in the developed world, and the direct medical costs of ADRs exceed $100 billion annually in the United States alone. Pharmacogenomics research seeks to identify genetic factors that are responsible for individual differences in drug efficacy and susceptibility to ADRs. This has led to several genetic tests that are currently being used to provide clinical recommendations. The Canadian Pharmacogenomics Network for Drug Safety is a nation-wide effort established in Canada to identify novel predictive genomic markers of severe ADRs in children and adults. A surveillance network has been established in 17 of Canada's major hospitals to identify patients experiencing specific ADRs and to collect biological samples and relevant clinical history for genetic association studies. To identify ADR-associated genetic markers that could be incorporated into predictive tests that will reduce the occurrence of serious ADRs, high-throughput genomic analyses are conducted with samples from patients that have suffered serious ADRs and matched control patients.
ADRs represent a significant unmet medical problem with significant morbidity and mortality, and Canadian Pharmacogenomics Network for Drug Safety is a nation-wide network in Canada that seeks to identify genetic factors responsible for interindividual differences in susceptibility to serious ADRs.
Active ADR surveillance is necessary to identify and recruit patients who suffer from serious ADRs. National and international collaborations are required to recruit sufficient patients for these studies. Several pharmacogenomics tests are currently in clinical use to provide dosing recommendations, and the number of pharmacogenomics tests is expected to significantly increase in the future.
Our primary objective was to evaluate demographic and causal factors of inhospital mortality for significant firearm-related injuries (i.e., those with an Injury Severity Score [ISS] > 12) in Canadian trauma centres.
We analyzed data submitted to the Canadian Institute for Health Information (CIHI) in the National Trauma Registry for all firearm-injured patients for fiscal years 1999-2003. Univariate and bivariate adjusting for ISS and multivariate logistic regression were performed.
Men accounted for 94% of the 784 injured. In all patients, the percentages of self-inflicted, intentional, unintentional and unknown injuries were 27.8%, 60.3%, 6.1% and 5.7%, respectively. The inhospital fatality rate was 39.8%, with 83% of fatalities occurring on the first day. Two-thirds of patients were discharged home. Univariate and adjusted analysis found that ISS, first systolic blood pressure (BP), first systolic BP under 100, first Glasgow Coma Scale (GCS) score, age over 45 years, self-inflicted injury, intentional injury and injury at home significantly worsened the odds ratio of death in hospital and that police shooting was relatively beneficial. BP under 100, age over 45 years and a low GCS score had an adjusted odds ratio of death of 4.12, 1.99 and 0.64 per point increase, respectively. The multivariate model showed that ISS, BP under 100, first GCS score, sex and self-inflicted injury were significant in predicting inhospital death.
A predominance of young men are injured intentionally with handguns in Canada, whereas older patients suffer self-inflicted injuries with long guns. The significant number of firearm deaths, largely in the first day, highlights the importance of preventative strategies and the need for rapid transport of patients to trauma centres for urgent care.
Cites: Am J Epidemiol. 1991 Sep 1;134(5):511-211897507
Statins reduce cardiovascular morbidity and mortality in appropriately selected patients. However, statin-associated myopathy is a significant risk associated with these agents. Recently, variation in the SLCO1B1 gene was reported to predict simvastatin-associated myopathy. The aim of this study was to replicate association of the rs4149056 variant in SLCO1B1 with severe statin-associated myopathy in a cohort of patients using a variety of statin medications and to investigate the association with specific statin types. We identified 25 cases of severe statin-associated myopathy and 84 controls matched for age, gender, statin type and dose. The rs4149056 variant in SLCO1B1 was not significantly associated with myopathy in this group as a whole. However, when subjects were stratified by statin type, the SLCO1B1 rs4149056 genotype was significantly associated with myopathy in patients who received simvastatin, but not in patients who received atorvastatin. Our findings provide further support for a role for SLCO1B1 genotype in simvastatin-associated myopathy, and suggest that this association may be stronger for simvastatin compared with atorvastatin.
A striking failure of modern medicine is the debilitating and lethal consequences of adverse drug reactions (ADRs), which rank as one of the top 10 leading causes of death and illness in the developed world with direct medical costs of 137-177 billion annually US dollars in the USA. Although many factors influence the effect of medications (e.g., age, organ function, drug interactions), genetic factors account for 20% to 95% of drug response variability and play a significant role in the incidence and severity of ADRs. The field of pharmacogenomics seeks to identify genetic factors responsible for individual differences in drug efficacy and ADRs. Pharmacogenomics has led to several genetic tests that provide clinical dosing recommendations. The Genetic Approaches to Therapy in Children (GATC) project is a national project established in Canada to identify novel predictive genomic markers for severe ADRs in children. An ADR surveillance network has been established in eight of Canada's major children's hospitals, serving up to 75% of all Canadian children. The goal of the project is to identify patients experiencing specific ADRs and matched controls, collect DNA samples, and apply genomics-based technologies to identify ADR-associated genetic markers with the goal of preventing serious ADRs in susceptible children.
Adverse drug reactions (ADRs) are a major cause of morbidity and mortality in children. Current models of ADR surveillance have repeatedly demonstrated little pragmatic value to practicing clinicians. ADR reporting rates in the US and Canada suggest that only 5% of ADRs are reported. The Genotypic Approaches to Therapy in Children (GATC) network was established to identify and solve drug safety problems in paediatrics. We hypothesized that genetic polymorphisms underlie a significant portion of concentration-dependent ADRs in children. Our objective was to establish an ADR active surveillance network in paediatric hospitals across Canada. Surveillance clinicians evaluate clinical information from ADR cases and drug-matched controls, and collected DNA samples from all patients. The surveillance network will enable the identification of predictive genomic-markers for ADRs. With this knowledge, children at risk can be identified before therapy is initiated and enable personalized adjustments to therapy based on genetic make-up.