The prevention and management of chronic disease in primary care: recommendations from a knowledge translation meeting

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. CONCLUSION: 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

UMD-CFTR: A database dedicated to CF and CFTR-related disorders

International audienceWith the increasing knowledge of cystic fibrosis (CF) and CFTR-related diseases (CFTR-RD), the number of sequence variations in the CFTR gene is constantly raising. CF and particularly CFTR-RD provide a particular challenge because of many unclassified variants and identical genotypes associated with different phenotypes. Using the Universal Mutation Database (UMD) software we have constructed UMD-CFTR (freely available at the URL: http://www.umd.be/CFTR/), the first comprehensive relational CFTR database that allows an in-depth analysis and annotation of all variations identified in individuals whose CFTR genes have been analyzed extensively. The system has been tested on the molecular data from 757 patients (540 CF and 217 CBAVD) including disease-causing, unclassified, and nonpathogenic alterations (301 different sequence variations) representing 3,973 entries. Tools are provided to assess the pathogenicity of mutations. UMD-CFTR also offers a number of query tools and graphical views providing instant access to the list of mutations, their frequencies, positions and predicted consequences, or correlations between genotypes, haplotypes, and phenotypes. UMD-CFTR offers a way to compile not only disease-causing genotypes but also haplotypes. It will help the CFTR scientific and medical communities to improve sequence variation interpretation, evaluate the putative influence of haplotypes on mutations, and correlate molecular data with phenotypes

Altered expression of cell proliferation-related and interferon-stimulated genes in colon cancer cells resistant to SN38

International audienceIrinotecan is a topoisomerase I inhibitor widely used as an anticancer agent in the treatment of metastatic colon cancer. However, its efficacy is often limited by the development of resistance. We have isolated a colon carcinoma cell line, HCT116-SN6, which displays a 6-fold higher resistance to SN38, the active metabolite of irinotecan. In this paper, we studied the molecular mechanisms that cause resistance to SN38 in the HCT116-SN6 cell line. First, we analyzed proliferation, cell cycle distribution, apoptosis, topoisomerase I expression and activity in SN38-resistant (HCT116-SN6) and sensitive (HCT116-s cells). We showed that the SN38-induced apoptosis and the SN38-activated cell cycle checkpoints leading to G(2)/M cell cycle arrest were similar in both cell lines. Topoisomerase I expression and catalytic activity were also unchanged. Then, we compared mRNA expression profiles in the two cell lines using the Affymetrix Human Genome GeneChip arrays U133A and B. Microarray analysis showed that among the genes, which were differentially expressed in HCT116-s and HCT116-SN6 cells, 27% were related to cell proliferation suggesting that proliferation might be the main target in the development of resistance to SN38. This result correlates with the phenotypic observation of a reduced growth rate in HCT116-SN6 resistant cells. Furthermore, 29% of the overexpressed genes were Interferon Stimulated Genes and we demonstrate that their overexpression is, at least partially, due to endogenous activation of the p38 MAP kinase pathway in SN38 resistant cells. In conclusion, a slower cell proliferation rate may be a major cause of acquired resistance to SN38 via a reduction of cell cycle progression through the S phase which is mandatory for the cytotoxic action of SN38. This lower growth rate could be due to the endogenous activation of p38