Participation in an action research project on vaccine services for children: relationship with vaccine delays.

Multicomponent interventions are effective in improving vaccine coverage. However, few studies have assessed their effect on timely vaccination. The aim of this study was to compare the proportion of children with vaccine delays at 2- and 12-month visits according to whether or not health centers have participated in an action research project on the organization of vaccination services for 0-5-year-olds. The action research project included a multicomponent intervention and was conducted between 2011 and 2015 in Quebec, Canada. An ecological before/after design was used for this analysis. A total of 264,579 DTaP-IPV-Hib (2-month visits) and 240,541 Men-C-C (12-month visits) vaccine doses were administered during 2011-2012 to 2014-2015 fiscal years, including 19% in 14 participating health centers and the remaining in 78 nonparticipating centers. Vaccine delays demonstrated a more pronounced decreasing trend in participating versus nonparticipating health centers (p < .0001 at 2 and 12 months). Between 2011-2012 and 2014-2015, participating centers managed to eliminate 35% of their vaccine delays at 2-month visits and 33% at 12-month visits, whereas nonparticipating centers eliminated 19% of delays at both visits. Our results are consistent with a positive impact of the multicomponent intervention, despite the fact that it had not specifically aimed at decreasing vaccine delays.

Identification of rare genetic variants in novel loci associated with Paget's disease of bone.

In genome-wide association studies, single nucleotide polymorphisms located in five novel loci were associated with PDB. We aimed at identifying rare genetic variants of candidate genes located in these loci and search for genetic association with PDB in the French-Canadian population. Exons, promoter and exon-intron junctions from patients with familial PDB and healthy individuals were sequenced in candidate genes, located within novel loci associated with PDB in our population. Rare variant was defined by a minor allele frequency <0.05 or absent from dbSNP (NCBI). We sequenced seven genes in 1p13 locus, three genes in 7q33, three genes in 8q22, and five genes in 15q24 locus. We identified 126 rare variants in at least one patient with PDB of whom 55 were located in 1p13 locus, 32 in 7q33, 10 in 8q22 and 29 in 15q24 locus. We located 71 of these 126 rare variants in an intron, 30 in an exon and 9 in an untranslated region. 60 % of these variants were located in functionally relevant gene regions. Among the 12 missense rare variants in PDB, two (rs62620995 in TM7SF4; rs62641691 in CD276) were predicted to be damaging by in silico analysis tools. Rs62620995, which altered a conserved amino acid (p.Leu397Phe) in the TM7SF4 gene, encoding the DC-STAMP protein involved in osteoclastogenesis through RANK signaling pathway, was found to have a marginal association with PDB (p = 0.09). Rs35500845, located in the CTHRC1 gene, which encodes a regulator of collagen matrix deposition, was also associated with PDB in the French-Canadian population (p = 0.046).

Genetic association study of Dickkopf-1 and sclerostin genes with paget disease of bone.

Increased expression of DKK1 gene was reported in pagetic osteoblasts and stromal cells, and increased serum levels of DKK1 and SOST proteins were reported in patients with Paget disease of bone (PDB). This study aimed at identifying rare genetic variants of the DKK1 and SOST genes and at testing for genetic association with PDB in the French-Canadian population. Exons, promoters, and exon-intron junctions of these genes were sequenced in patients with PDB and healthy controls. An association study of Tag SNPs of both genes was also performed in 239 pagetic patients and 297 healthy individuals. Three rare variants were identified in this study, all located in the DKK1 gene: one variant in the second exon leading to alteration in a highly conserved amino acid (p.R120L), one in the 5'-untranslated region (-50 C/A), and one in a splice site of intron 1 (IVS1 184 T/C), although none of these rare variants were associated with PDB. A genetic association of a Tag SNP of the DKK1 gene was found: the G allele of rs1569198 was significantly decreased in patients in comparison to controls (42 vs. 49 %, uncorrected P = 0.03, OR = 0.77, 95 % CI 0.61-0.98). In conclusion, this study identified three rare genetic variants in DKK1 in the French-Canadian population. In addition, a weak genetic association of a common variant of DKK1, rs1569198, which is located on a predicted new acceptor site for splicing of this gene, was observed in PDB, whereas no rare variant or genetic association was found in the SOST gene.