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Background: Cancer is the leading cause of death in Canada. Early cancer diagnosis could improve patients' prognosis and quality of life. This study aimed to analyze the factors influencing elapsed time between the first help-seeking trigger and cancer diagnosis with respect to the three most common and deadliest cancer types: lung, breast, and colorectal.Methods: This paper presents the qualitative component of a larger project based on a sequential explanatory design. Twenty-two patients diagnosed were interviewed, between 2011 to 2013, in oncology clinics of four hospitals in the two most populous regions in Quebec (Canada). Transcripts were analyzed using the Model of Pathways to Treatment.Results: Pre-diagnosis elapsed time and phases are difficult to appraise precisely and vary according to cancer sites and symptoms specificity. This observation makes the Model of Pathways to Treatment challenging to use to analyze patients' experiences. Analyses identified factors contributing to elapsed time that are linked to type of cancer, to patients, and to health system organization.Conclusions: This research allowed us to identify avenues for reducing the intervals between first symptoms and cancer diagnosis. The existence of inequities in access to diagnostic services, even in a universal healthcare system, was highlighted. [ABSTRACT FROM AUTHOR]

Background: Prenatal alcohol exposure is the leading preventable cause of behavioral and cognitive deficits, which may affect between 2 and 5 % of children in North America. While the underlying mechanisms of alcohol's effects on development remain relatively unknown, emerging evidence implicates epigenetic mechanisms in mediating the range of symptoms observed in children with fetal alcohol spectrum disorder (FASD). Thus, we investigated the effects of prenatal alcohol exposure on genome-wide DNA methylation in the NeuroDevNet FASD cohort, the largest cohort of human FASD samples to date. Methods: Genome-wide DNA methylation patterns of buccal epithelial cells (BECs) were analyzed using the Illumina HumanMethylation450 array in a Canadian cohort of 206 children (110 FASD and 96 controls). Genotyping was performed in parallel using the Infinium HumanOmni2.5-Quad v1.0 BeadChip. Results: After correcting for the effects of genetic background, we found 658 significantly differentially methylated sites between FASD cases and controls, with 41 displaying differences in percent methylation change >5 %. Furthermore, 101 differentially methylated regions containing two or more CpGs were also identified, overlapping with 95 different genes. The majority of differentially methylated genes were highly expressed at the level of mRNA in brain samples from the Allen Brain Atlas, and independent DNA methylation data from cortical brain samples showed high correlations with BEC DNA methylation patterns. Finally, overrepresentation analysis of genes with up-methylated CpGs revealed a significant enrichment for neurodevelopmental processes and diseases, such as anxiety, epilepsy, and autism spectrum disorders. Conclusions: These findings suggested that prenatal alcohol exposure is associated with distinct DNA methylation patterns in children and adolescents, raising the possibility of an epigenetic biomarker of FASD. [ABSTRACT FROM AUTHOR]

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Background: Seven chronic disease prevention and management programs were implemented across Quebec with funding support from a provincial-private industry funding initiative. Given the complexity of implementing integrated primary care chronic disease management programs, a knowledge transfer meeting was held to share experiences across programs and synthesize common challenges and success factors for implementation. Methods: The knowledge translation meeting was held in February 2014 in Montreal, Canada. Seventy-five participants consisting of 15 clinicians, 14 researchers, 31 knowledge users, and 15 representatives from the funding agencies were broken up into groups of 10 or 11 and conducted a strengths, weaknesses, opportunities, and threats analysis on either the implementation or the evaluation of these chronic disease management programs. Results were reported back to the larger group during a plenary and recorded. Audiotapes were transcribed and summarized using pragmatic thematic analysis. Results and discussion: Strengths to leverage for the implementation of the seven programs include: (1) synergy between clinical and research teams; (2) stakeholders working together; (3) motivation of clinicians; and (4) the fact that the programs are evidence-based. Weaknesses to address include: (1) insufficient resources; (2) organizational change within the clinical sites; (3) lack of referrals from primary care physicians; and (4) lack of access to programs. Strengths to leverage for the evaluation of these programs include: (1) engagement of stakeholders and (2) sharing of knowledge between clinical sites. Weaknesses to address include: (1) lack of referrals; (2) difficulties with data collection; and (3) difficulties in identifying indicators and control groups. Opportunities for both themes include: (1) fostering new and existing partnerships and stakeholder relations; (2) seizing funding opportunities; (3) knowledge transfer; (4) supporting the transformation of professional roles; (5) expand the use of health information technology; and (6) conduct cost evaluations. Fifteen recommendations related to mobilisation of primary care physicians, support for the transformation of professional roles, and strategies aimed at facilitating the implementation and evaluation of chronic disease management programs were formulated based on the discussions at this knowledge translation event. The results from this knowledge translation day will help inform the sustainability of these seven chronic disease management programs in Quebec and the implementation and evaluation of similar programs elsewhere. [ABSTRACT FROM AUTHOR]

Background Along with the improvement of high throughput sequencing technologies, the genetics community is showing marked interest for the rare variants/common diseases hypothesis. While sequencing can still be prohibitive for large studies, commercially available genotyping arrays targeting rare variants prove to be a reasonable alternative. A technical challenge of array based methods is the task of deriving genotype classes (homozygous or heterozygous) by clustering intensity data points. The performance of clustering tools for common polymorphisms is well established, while their performance when conducted with a large proportion of rare variants (where data points are sparse for genotypes containing the rare allele) is less known. We have compared the performance of four clustering tools (GenCall, GenoSNP, optiCall and zCall) for the genotyping of over 10,000 samples using the Illumina's HumanExome BeadChip, which includes 247,870 variants, 90% of which have a minor allele frequency below 5%in a population of European ancestry. Different reference parameters for GenCall and different initial parameters for GenoSNP were tested. Genotyping accuracy was assessed using data from the 1000 Genomes Project as a gold standard, and agreement between tools was measured. Results Concordance of GenoSNP's calls with the gold standard was below expectations and was increased by changing the tool's initial parameters. While the four tools provided concordance with the gold standard above 99% for common alleles, some of them performed poorly for rare alleles. The reproducibility of genotype calls for each tool was assessed using experimental duplicates which provided concordance rates above 99%. The inter-tool agreement of genotype calls was high for approximately 95% of variants. Most tools yielded similar error rates (approximately 0.02), except for zCall which performed better with a 0.00164 mean error rate. Conclusions The GenoSNP clustering tool could not be run straight "out of the box" with the HumanExome BeadChip, as modification of hard coded parameters was necessary to achieve optimal performance. Overall, GenCall marginally outperformed the other tools for the HumanExome BeadChip. The use of experimental replicates provided a valuable quality control tool for genotyping projects with rare variants. [ABSTRACT FROM AUTHOR]

Background: The Canadian healthcare system is currently experiencing important organizational transformations through the reform of primary healthcare (PHC). These reforms vary in scope but share a common feature of proposing the transformation of PHC organizations by implementing new models of PHC organization. These models vary in their performance with respect to client affiliation, utilization of services, experience of care and perceived outcomes of care. Objectives: In early 2005 we conducted a study in the two most populous regions of Quebec province (Montreal and Montérégie) which assessed the association between prevailing models of primary healthcare (PHC) and population-level experience of care. The goal of the present research project is to track the evolution of PHC organizational models and their relative performance through the reform process (from 2005 until 2010) and to assess factors at the organizational and contextual levels that are associated with the transformation of PHC organizations and their performance. Methods/Design: This study will consist of three interrelated surveys, hierarchically nested. The first survey is a population-based survey of randomly-selected adults from two populous regions in the province of Quebec. This survey will assess the current affiliation of people with PHC organizations, their level of utilization of healthcare services, attributes of their experience of care, reception of preventive and curative services and perception of unmet needs for care. The second survey is an organizational survey of PHC organizations assessing aspects related to their vision, organizational structure, level of resources, and clinical practice characteristics. This information will serve to develop a taxonomy of organizations using a mixed methods approach of factorial analysis and principal component analysis. The third survey is an assessment of the organizational context in which PHC organizations are evolving. The five year prospective period will serve as a natural experiment to assess contextual and organizational factors (in 2005) associated with migration of PHC organizational models into new forms or models (in 2010) and assess the impact of this evolution on the performance of PHC. Discussion: The results of this study will shed light on changes brought about in the organization of PHC and on factors associated with these changes. [ABSTRACT FROM AUTHOR]

Background: Healthcare reforms initiated in the early 2000s in Québec involved the implementation of new modes of primary healthcare (PHC) delivery and the creation of Health and Social Services Centers (HSSCs) to support it. The objective of this article is to assess and explain the degree of PHC organizational change achieved following these reforms.Methods: We conducted two surveys of PHC organizations, in 2005 and 2010, in two regions of the province of Québec, Canada. From the responses to these surveys, we derived a measure of organizational change based on an index of conformity to an ideal type (ICIT). One set of explanatory variables was contextual, related to coercive, normative and mimetic influences; the other consisted of organizational variables that measured receptivity towards new PHC models. Multilevel analyses were performed to examine the relationships between ICIT change in the post-reform period and the explanatory variables.Results: Positive results were attained, as expressed by increase in the ICIT score in the post-reform period, mainly due to implementation of new types of PHC organizations (Family Medicine Groups and Network Clinics). Organizational receptivity was the main explanatory variable mediating the effect of coercive and mimetic influences. Normative influence was not a significant factor in explaining changes.Conclusion: Changes were modest at the system level but important with regard to new forms of PHC organizations. The top-down decreed reform was a determining factor in initiating change whereas local coercive and normative influences did not play a major role. The exemplar role played by certain PHC organizations through mimetic influence was more important. Receptivity of individual organizations was both a necessary condition and a mediating factor in influencing change. This supports the view that a combination of top-down and bottom-up strategy is best suited for achieving substantial changes in PHC local organization. [ABSTRACT FROM AUTHOR]

Background: The goal of this project is to evaluate the implementation of an integrated and interdisciplinary program for prevention and management of cardiometabolic risk (PCMR). The intervention is based on the Chronic Care Model. The study will evaluate the implementation of the PCMR in 6 of the 12 health and social services centres (CSSS) in Montréal, and the effects of the PCMR on patients and the practice of their primary care physicians up to 40 months following implementation, as well as the sustainability of the program. Objectives are: 1-to evaluate the effects of the PCMR and their persistence on patients registered in the program and the practice of their primary care physicians, by implementation site and degree of exposure to the program; 2-to assess the degree of implementation of PCMR in each CSSS territory and identify related contextual factors; 3-to establish the relationships between the effects observed, the degree of PCMR implementation and the related contextual factors; 4-to assess the impact of the PCMR on strengthening local services networks., Methods/design: The evaluation will use a mixed design that includes two complementary research strategies. The first strategy is similar to a quasi-experimental "before-after" design, based on a quantitative approach; it will look at the program's effects and their variations among the six territories. The effects analysis will use data from a clinical database and from questionnaires completed by participating patients and physicians. Over 3000 patients will be recruited. The second strategy corresponds to a multiple case study approach, where each of the six CSSS constitutes a case. With this strategy, qualitative methods will set out the context of implementation using data from semi-structured interviews with program managers. The quantitative data will be analyzed using linear or multilevel models complemented with an interpretive approach to qualitative data analysis., Discussion: Our study will identify contextual factors associated with the effectiveness, successful implementation and sustainability of such a program. The contextual information will enable us to extrapolate our results to other contexts with similar conditions., Trial Registration: ClinicalTrials.gov: NCT01326130.