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1.  Anti-nucleosome antibodies outperform traditional biomarkers as longitudinal indicators of disease activity in systemic lupus erythematosus 
Rheumatology (Oxford, England)  2014;54(3):449-457.
Objective. The aim of this study was to determine whether anti-nucleosome antibodies function as activity-specific biomarkers in SLE.
Methods. Fifty-one patients were recruited and followed prospectively with periodic clinical and biochemical assessments over a 14-month period. Disease activity was determined by the SLEDAI-2K. Anti-nucleosome antibody levels were measured by an ELISA and its utility as an activity-specific biomarker as compared with that of anti-dsDNA antibodies and C3 was assessed both at baseline and in longitudinal analysis.
Results. Anti-nucleosome antibodies were significantly elevated in SLE patients vs controls and showed a moderate positive correlation with disease activity. The utility of anti-nucleosome antibodies in identifying patients with active disease in a cross-sectional analysis was comparable to that of anti-dsDNA antibodies and C3. Analysis of variance demonstrated that the level of anti-nucleosome antibodies and C3 varied significantly with changes in disease activity over time. Changes in clinical state were not mirrored by changes in anti-dsDNA antibodies. In time-dependent analysis, anti-nucleosome antibodies showed a better fit over time than anti-dsDNA antibodies and C3. In pairwise comparisons, C3 and anti-nucleosome antibodies outperformed other models, including the conventional pairing of C3 and anti-dsDNA antibodies, however, no biomarker alone or as a group accurately predicted impending remissions or exacerbations.
Conclusion. Anti-nucleosome antibodies demonstrate greater fidelity as a biomarker for changes in SLE disease activity than traditional biomarkers, supporting the routine monitoring of this antibody in clinical practice.
PMCID: PMC4334682  PMID: 25193804
systemic lupus erythematosus; anti-nucleosome antibodies; biomarkers; disease activity
2.  The Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort study: assessment of environmental exposures 
The Canadian Healthy Infant Longitudinal Development birth cohort was designed to elucidate interactions between environment and genetics underlying development of asthma and allergy. Over 3600 pregnant mothers were recruited from the general population in four provinces with diverse environments. The child is followed to age 5 years, with prospective characterization of diverse exposures during this critical period. Key exposure domains include indoor and outdoor air pollutants, inhalation, ingestion and dermal uptake of chemicals, mold, dampness, biological allergens, pets and pests, housing structure, and living behavior, together with infections, nutrition, psychosocial environment, and medications. Assessments of early life exposures are focused on those linked to inflammatory responses driven by the acquired and innate immune systems. Mothers complete extensive environmental questionnaires including time-activity behavior at recruitment and when the child is 3, 6, 12, 24, 30, 36, 48, and 60 months old. House dust collected during a thorough home assessment at 3–4 months, and biological specimens obtained for multiple exposure-related measurements, are archived for analyses. Geo-locations of homes and daycares and land-use regression for estimating traffic-related air pollution complement time-activity-behavior data to provide comprehensive individual exposure profiles. Several analytical frameworks are proposed to address the many interacting exposure variables and potential issues of co-linearity in this complex data set.
PMCID: PMC4611361  PMID: 25805254
environmental exposure assessment; longitudinal birth cohort; indoor air quality; etiology of asthma; biomarkers; CHILD study
3.  Approaching Etuaptmumk – introducing a consensus-based mixed method for health services research 
International Journal of Circumpolar Health  2015;74:10.3402/ijch.v74.27438.
With the recognized need for health systems’ improvements in the circumpolar and indigenous context, there has been a call to expand the research agenda across all sectors influencing wellness and to recognize academic and indigenous knowledge through the research process. Despite being recognized as a distinct body of knowledge in international forums and across indigenous groups, examples of methods and theories based on indigenous knowledge are not well documented in academic texts or peer-reviewed literature on health systems. This paper describes the use of a consensus-based, mixed method with indigenous knowledge by an experienced group of researchers and indigenous knowledge holders who collaborated on a study that explored indigenous values underlying health systems stewardship. The method is built on the principles of Etuaptmumk or two-eyed seeing, which aim to respond to and resolve the inherent conflicts between indigenous ways of knowing and the scientific inquiry that informs the evidence base in health care. Mixed methods’ frameworks appear to provide a framing suitable for research questions that require data from indigenous knowledge sources and western knowledge. The nominal consensus method, as a western paradigm, was found to be responsive to embedding of indigenous knowledge and allowed space to express multiple perspectives and reach consensus on the question at hand. Further utilization and critical evaluation of this mixed methodology with indigenous knowledge are required.
PMCID: PMC4442124  PMID: 26004427
health systems stewardship; indigenous values; mixed methods
4.  Impact of a chronic disease self-management program on health care utilization in rural communities: a retrospective cohort study using linked administrative data 
Internationally, chronic disease self-management programs (CDSMPs) have been widely promoted with the assumption that confident, knowledgeable patients practicing self-management behavior will experience improved health and utilize fewer healthcare resources. However, there is a paucity of published data supporting this claim and the majority of the evidence is based on self-report.
We used a retrospective cohort study using linked administrative health data. Data from 104 tele-CDSMP participants from 13 rural and remote communities in the province of Ontario, Canada were linked to administrative databases containing emergency department (ED) and physician visits and hospitalizations. Patterns of health care utilization prior to and after participation in the tele-CDSMP were compared. Poisson Generalized Estimating Equations regression was used to examine the impact of the tele-CDSMP on health care utilization after adjusting for covariates.
There were no differences in patterns of health care utilization before and after participating in the tele-CDSMP. Among participants ≤ 66 years, however, there was a 34% increase in physician visits in the 12 months following the program (OR = 1.34, 95% CI 1.11-1.61) and a trend for decreased ED visits in those >66 years (OR = 0.59, 95% CI 0.33-1.06).
This is the first study to examine health care use following participation in the CDSMP in a Canadian population and to use administrative data to measure health care utilization. Similar to other studies that used self-report measures to evaluate health care use we found no differences in health care utilization before and after participation in the CDSMP. Future research needs to confirm our findings and examine the impact of the CDSMP on health care utilization in different age groups to help to determine whether these interventions are more effective with select population groups.
PMCID: PMC4036726  PMID: 24885135
5.  Canadians’ Perceptions of Food, Diet, and Health – A National Survey 
PLoS ONE  2014;9(1):e86000.
Poor nutrition is harmful to one’s health as it can lead to overweight and obesity and a number of chronic diseases. Understanding consumer perceptions toward diet and nutrition is critical to advancing nutrition-related population health interventions to address such issues. The purpose of this paper was to examine Canadians’ perceived health and diet status, compared to their actual health status, and general concern about their own diet and beliefs about health. Also analyzed were some of the perceived barriers to eating “healthy” foods, with a focus on the availability of “healthy” processed foods.
Two surveys were administered online to a group of Canadian panelists from all ten provinces during May 2010 to January 2011. Thirty thousand were invited; 6,665 completed the baseline survey and 5,494 completed the second survey. Panelists were selected to be nationally representative of the Canadian adult population by age, sex, province and education level, according to 2006 census data.
Approximately one third of Canadians perceived their health or diet to be very good while very few Canadians perceived their health or diet to be very poor. While the majority of Canadians believed food and nutrition to be very important for improving one’s health, fewer Canadians were concerned about their own diets. The majority of Canadians reported difficulty finding “healthy” processed foods (low in salt and sugar and with sufficient vitamins and minerals). Many also reported difficulty finding healthy foods that are affordable.
Although consumers believe that nutrition is one of the most important factors for maintaining health, there are still a number of attitudinal and perceived environmental barriers to healthy eating.
PMCID: PMC3900450  PMID: 24465832
6.  Food products qualifying for and carrying front-of-pack symbols: a cross-sectional study examining a manufacturer led and a non-profit organization led program 
BMC Public Health  2013;13:846.
Concern has been raised that the coexistence of multiple front-of-pack (FOP) nutrition rating systems in a marketplace may mislead consumers into believing that a specific food with a FOP is ‘healthier’ than foods without the symbol. Eleven summary indicator FOP systems are in use in Canada, including one non-profit developed system, the Heart and Stroke Foundation’s Health Check™, and ten manufacturer-developed systems, like Kraft’s Sensible Solutions™. This study evaluated FOP’s potential to mislead consumers by comparing the number of products qualifying to carry a given FOP symbol to the number of products that actually carry the symbol.
The nutritional criteria for the Health Check™ and the Sensible Solutions™ systems were applied to a 2010–2011 Canadian national database of packaged food products. The proportion of foods qualifying for a given FOP system was compared to the proportion carrying the symbol using McNemar’s test.
Criteria were available to categorize 7503 and 3009 of the 10,487 foods in the database under Health Check™ and Sensible Solutions™, respectively. Overall 45% of the foods belonging to a Health Check™ category qualified for Health Check’s™ symbol, while only 7.5% of the foods carried the symbol. Up to 79.1% of the foods belonging to a Sensible Solutions™, category qualified for Sensible Solutions’s™ symbol while only 4.1% of the foods carried the symbol. The level of agreement between products qualifying for and carrying FOP systems was poor to moderate in the majority of food categories for both systems. More than 75% of the products in 24 of the 85 Health Check™ subcategories and 9 of 11 Sensible Solution™ categories/subcategories qualified for their respective symbols based on their nutritional composition.
FOP systems as they are currently applied are not, in most instances, a useful guide to identifying healthier food products in the supermarket as many more products qualify for these systems than the number of products actually displaying these symbols on FOP, and the level of agreement between qualifying and carrying products is poor to moderate. The adoption of a single, standardized FOP system would assure consumers that all products meeting certain nutritional standards are designated by the symbol.
PMCID: PMC3847373  PMID: 24034717
Nutrition labelling; Front-of-pack nutrition rating systems; Nutrient criteria
7.  Increasing Access to Chronic Disease Self-Management Programs in Rural and Remote Communities Using Telehealth 
Telemedicine Journal and e-Health  2013;19(6):467-473.
Objective: This study examined whether a telehealth chronic disease self-management program (CDSMP) would lead to improvements in self-efficacy, health behaviors, and health status for chronically ill adults living in Northern Ontario, Canada. Two telehealth models were used: (1) single site, groups formed by participants at one telehealth site; and (2) multi-site, participants linked from multiple sites to form one telehealth group, as a strategy to increase access to the intervention for individuals living in rural and remote communities. Subjects and Methods: Two hundred thirteen participants diagnosed with heart disease, stroke, lung disease, or arthritis attended the CDSMP at a preexisting Ontario Telemedicine Network studio from September 2007 to June 2008. The program includes six weekly, peer-facilitated sessions designed to help participants develop important self-management skills to improve their health and quality of life. Baseline and 4-month follow-up surveys were administered to assess self-efficacy beliefs, health behaviors, and health status information. Results were compared between single- and multi-site delivery models. Results: Statistically significant improvements from baseline to 4-month follow-up were found for self-efficacy (6.6±1.8 to 7.0±1.8; p<0.001), exercise behavior, cognitive symptom management, communication with physicians, role function, psychological well-being, energy, health distress, and self-rated health. There were no statistically significant differences in outcomes between single- and multi-site groups. Conclusions: Improvements in self-efficacy, health status, and health behaviors were equally effective in single- and multi-site groups. Access to self-management programs could be greatly increased with telehealth using single- and multi-site groups in rural and remote communities.
PMCID: PMC3696947  PMID: 23570277
telehealth; policy; cardiology/cardiovascular disease; self-care
8.  Clinically relevant hormone treatments fail to induce spinogenesis in prefrontal cortex of aged female rhesus monkeys 
Preclinical animal models have provided strong evidence that estrogen therapy (ET) enhances cognition and induces spinogenesis in neuronal circuits. However, clinical studies have been inconsistent, with some studies revealing adverse effects of ET, including an increased risk of dementia. In an effort to bridge this disconnect between the preclinical and clinical data, we have developed a non-human primate (NHP) model of ET combined with high-resolution dendritic spine analysis of dorsolateral prefrontal cortical (dlPFC) neurons. Previously, we reported cyclic ET in aged, ovariectomized NHPs increased spine density on dlPFC neurons. Here, we report that monkeys treated with cyclic E treatment paired with cyclic progesterone (P), continuous E combined with P (either cyclic or continuous), or unopposed continuous E failed to increase spines on dlPFC neurons. Given that the most prevalent form of ET prescribed to women is a combined and continuous E and P, these data bring into convergence the human neuropsychological findings and preclinical neurobiological evidence that standard hormone therapy in women is unlikely to yield the synaptic benefit presumed to underlie the cognitive enhancement reported in animal models.
PMCID: PMC3657730  PMID: 22915112
9.  Clinically Relevant Hormone Treatments Fail to Induce Spinogenesis in Prefrontal Cortex of Aged Female Rhesus Monkeys 
The Journal of Neuroscience  2012;32(34):11700-11705.
Preclinical animal models have provided strong evidence that estrogen (E) therapy (ET) enhances cognition and induces spinogenesis in neuronal circuits. However, clinical studies have been inconsistent, with some studies revealing adverse effects of ET, including an increased risk of dementia. In an effort to bridge this disconnect between the preclinical and clinical data, we have developed a nonhuman primate (NHP) model of ET combined with high-resolution dendritic spine analysis of dorsolateral prefrontal cortical (dlPFC) neurons. Previously, we reported cyclic ET in aged, ovariectomized NHPs increased spine density on dlPFC neurons. Here, we report that monkeys treated with cyclic E treatment paired with cyclic progesterone (P), continuous E combined with P (either cyclic or continuous), or unopposed continuous E failed to increase spines on dlPFC neurons. Given that the most prevalent form of ET prescribed to women is a combined and continuous E and P, these data bring into convergence the human neuropsychological findings and preclinical neurobiological evidence that standard hormone therapy in women is unlikely to yield the synaptic benefit presumed to underlie the cognitive enhancement reported in animal models.
PMCID: PMC3657730  PMID: 22915112
10.  Will Mobile Diabetes Education Teams (MDETs) in primary care improve patient care processes and health outcomes? Study protocol for a randomized controlled trial 
Trials  2012;13:165.
There is evidence to suggest that delivery of diabetes self-management support by diabetes educators in primary care may improve patient care processes and patient clinical outcomes; however, the evaluation of such a model in primary care is nonexistent in Canada. This article describes the design for the evaluation of the implementation of Mobile Diabetes Education Teams (MDETs) in primary care settings in Canada.
This study will use a non-blinded, cluster-randomized controlled trial stepped wedge design to evaluate the Mobile Diabetes Education Teams' intervention in improving patient clinical and care process outcomes. A total of 1,200 patient charts at participating primary care sites will be reviewed for data extraction. Eligible patients will be those aged ≥18, who have type 2 diabetes and a hemoglobin A1c (HbA1c) of ≥8%. Clusters (that is, primary care sites) will be randomized to the intervention and control group using a block randomization procedure within practice size as the blocking factor. A stepped wedge design will be used to sequentially roll out the intervention so that all clusters eventually receive the intervention. The time at which each cluster begins the intervention is randomized to one of the four roll out periods (0, 6, 12, and 18 months). Clusters that are randomized into the intervention later will act as the control for those receiving the intervention earlier. The primary outcome measure will be the difference in the proportion of patients who achieve the recommended HbA1c target of ≤7% between intervention and control groups. Qualitative work (in-depth interviews with primary care physicians, MDET educators and patients; and MDET educators’ field notes and debriefing sessions) will be undertaken to assess the implementation process and effectiveness of the MDET intervention.
Trial registration NCT01553266
PMCID: PMC3519552  PMID: 22974080
Diabetes; Self-management education; Diabetes self-management support; Primary care; Cluster randomized controlled trial; Stepped wedge design; Inter-professional collaboration; Chronic disease models
11.  A pilot with computer-assisted psychosocial risk –assessment for refugees 
Refugees experience multiple health and social needs. This requires an integrated approach to care in the countries of resettlement, including Canada. Perhaps, interactive eHealth tools could build bridges between medical and social care in a timely manner. The authors developed and piloted a multi-risk Computer-assisted Psychosocial Risk Assessment (CaPRA) tool for Afghan refugees visiting a community health center. The iPad based CaPRA survey was completed by the patients in their own language before seeing the medical practitioner. The computer then generated individualized feedback for the patient and provider with suggestions about available services.
A pilot randomized trial was conducted with adult Afghan refugees who could read Dari/Farsi or English language. Consenting patients were randomly assigned to the CaPRA (intervention) or usual care (control) group. All patients completed a paper-pencil exit survey. The primary outcome was patient intention to see a psychosocial counselor. The secondary outcomes were patient acceptance of the tool and visit satisfaction.
Out of 199 approached patients, 64 were eligible and 50 consented and one withdrew (CaPRA = 25; usual care = 24). On average, participants were 37.6 years of age and had lived 3.4 years in Canada. Seventy-two percent of participants in CaPRA group had intention to visit a psychosocial counselor, compared to 46 % in usual care group [X2 (1)=3.47, p = 0.06]. On a 5-point scale, CaPRA group participants agreed with the benefits of the tool (mean = 4) and were ‘unsure’ about possible barriers to interact with the clinicians (mean = 2.8) or to privacy of information (mean = 2.8) in CaPRA mediated visits. On a 5-point scale, the two groups were alike in patient satisfaction (mean = 4.3).
The studied eHealth tool offers a promising model to integrate medical and social care to address the health and settlement needs of refugees. The tool’s potential is discussed in relation to implications for healthcare practice. The study should be replicated with a larger sample to generalize the results while controlling for potential confounders.
PMCID: PMC3461470  PMID: 22800506
Computer-assisted; Health assessment; Community health centre; Pilot; Controlled trial; Refugee
12.  Influence of Socioeconomic Status on Survival of Hepatocellular Carcinoma in the Ontario Population; A Population-Based Study, 1990–2009 
PLoS ONE  2012;7(7):e40917.
Research has shown that people from higher socioeconomic status (SES) have better hepatocellular carcinoma (HCC) survival outcomes, although no such research has been carried out in Canada. We aimed to assess if an association between SES and HCC survival existed in the Canadian context.
Methodology/Prinicpal Findings
We conducted a population-based cohort study linking HCC cases identified in the Ontario Cancer Registry between 1990 and 2009 to administrative and hospital data. Logistic regression and chi-squared tests were used to evaluate associations between SES (income quintile) and covariates. The Kaplan-Meier method was used to estimate survival. Sequential analysis of the proportional-hazards models were used to determine the association between SES and HCC survival controlling for potential prognostic covariates. During the period 1990–2009, 5,481 cases of HCC were identified. A significant association was found between SES and curative treatment (p = 0.0003), but no association was found between SES and non-curative treatment (p = 0.064), palliative treatment (p = 0.680), or ultrasound screening (p = 0.615). The median survival for the lowest SES was 8.5 months, compared to 8.8 months for the highest SES group. The age- and sex-adjusted proportional-hazards model showed statistically significant difference in HCC survival among the SES groups, with hazard ratio 0.905 (95% confidence intervals 0.821, 0.998) when comparing highest to lowest SES group. Further adjustments indicated that potentially curative treatment was the likely explanation for the association between SES and HCC survival.
Our findings suggest that a 10% HCC survival advantage exists for the higher SES groups. This association between SES and HCC survival is most likely a reflection of lack of access to care for low SES groups, revealing inequities in the Canadian healthcare system.
PMCID: PMC3396620  PMID: 22808283
13.  Estrogen Promotes Stress Sensitivity in a Prefrontal Cortex–Amygdala Pathway 
Cerebral Cortex (New York, NY)  2010;20(11):2560-2567.
We have recently reported in male rats that medial prefrontal cortex (mPFC) neurons that project to the basolateral nucleus of the amygdala (BLA) are resilient to stress-induced dendritic remodeling. The present study investigated whether this also occurs in female rats. This pathway was identified using the retrograde tracer Fast Blue injected into the BLA of ovariectomized female rats with estrogen replacement (OVX + E) and without (OVX + veh). Animals were exposed for 10 days either to 2-h immobilization stress or to home cage rest, after which layer III mPFC neurons that were either retrogradely labeled by Fast Blue or unlabeled were filled with Lucifer Yellow and analyzed for apical dendritic length and spine density. No dendritic remodeling occurred in unlabeled neurons from OVX + veh or OVX + E animals. In BLA-projecting neurons, however, stress had no effect on length in OVX + veh animals, but stressed OVX + E females showed greater dendritic length than controls at intermediate branches. Stress also caused an increase in spine density in all neurons in OVX + veh animals and a spine density increase in BLA-projecting neurons in OVX + E females. Estrogen also increased spine density on BLA-projecting neurons in unstressed animals. These data demonstrate both independent effects of estrogen on pyramidal cell morphology and effects that are interactive with stress, with the BLA-projecting neurons being sensitive to both kinds of effects.
PMCID: PMC2951843  PMID: 20139149
connectivity; dendritic arborization; medial prefrontal cortex; neural plasticity; sex difference
14.  Hyperbaric oxygen therapy and diabetic foot ulcers 
Canadian Family Physician  2010;56(5):444-452.
To explore physicians’ knowledge of and attitudes toward hyperbaric oxygen therapy (HBOT) in order to better understand current diabetic foot ulcer management practices and to determine potential barriers to HBOT use.
A 24-item questionnaire.
Primary Care Today conference in Toronto, Ont, in May of 2006.
Physician attendees, 313 of whom completed the survey.
Self-reported knowledge of and attitudes toward HBOT.
Less than 10% of respondents had a good knowledge of HBOT, but 57% had a good attitude toward HBOT. Knowledge of and attitude toward HBOT were positively correlated (P < .0001). Good knowledge of HBOT was associated with sex (P = .0334), age younger than 40 years (P = .0803), years in medical practice (P = .0646), patient requests for HBOT referrals (P = .0127), and having previously referred patients for HBOT (P < .001). Twenty years or more in medical practice (P = .0593) and receiving patient requests for HBOT (P = .0394) were multivariate predictors of having good knowledge of HBOT. Good attitude toward HBOT was associated with age younger than 40 years (P = .0613) and having previously referred patients for HBOT (P = .0013). Multivariate analysis showed that male physicians (P = .0026) received more patient requests for HBOT (P < .0001), had good knowledge (P = .0129) and a good attitude (P = .0488), and were more likely to refer patients for HBOT.
Primary care physicians have underdeveloped knowledge of HBOT, but their generally positive attitudes toward its use suggest that they might be receptive to educational interventions. Educating both physicians and patients about HBOT, specifically its cost-effectiveness, might encourage future use.
PMCID: PMC2868617  PMID: 20463275
15.  From gene networks underlying sex determination and gonadal differentiation to the development of neural networks regulating sociosexual behavior 
Brain research  2006;1126(1):109-121.
Genes are not expressed in isolation any more than social behavior has meaning outside of society. Both are in dynamic flux with the immediate environment that the gene/individual finds itself, which in turn establishes the timing, pattern, and conditions of expression. This means that complex behaviors and their genetic underpinnings should be viewed as a cumulative process, or as the result of experiences up to that point in time and, at the same time, as setting the stage for what will follow. The evidence indicates that as experiences accumulate throughout life, early experiences shape how genes/individuals will respond to later experiences, whereas later experiences modify the effects of these earlier experiences. A method of graphically representing and analyzing change in gene and neural networks is presented. Results from several animal model systems will be described to illustrate these methods. First, we will consider the phenomenon of temperature-dependent sex determination in reptiles. We will illustrate how the experience of a particular temperature during a sensitive period of embryogenesis sculpts not only the patterns of expression of genes involved in sex determination and gonadal differentiation but also the morphological, physiological, neuroendocrine, and behavioral traits of the adult phenotype. The second model system concerns the effects of the sex ratio in the litter in rats, and the genotype ratio in the litter of transgenic mice, on the nature and frequency of maternal care and how this in turn influences the patterns of activation of identified neural circuits subserving the offspring's sociosexual behavior when it is an adult.
PMCID: PMC2394678  PMID: 16905124
Reptile; Knockout mouse; Rat; Epigenetic; Cytochrome oxidase; Analysis

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