Overview of a formal scoping review on health system report cards

Background: There is an extensive body of literature on health system quality reporting that has yet to be characterized. Scoping is a novel methodology for systematically assessing the breadth of a body of literature in a particular research area. Our objectives were to showcase the scoping review methodology in the review of health system quality reporting, and to report on the extent of the literature in this area.Methods: A scoping review was performed based on the York methodology outlined by Arksey and O'Malley from the University of York, United Kingdom. We searched 14 peer reviewed and grey literature databases limiting the search to English language and non-English language articles with English abstracts published between 1980 and June 2006 with an update to November 2008. We also searched specific websites, reference lists, and key journals for relevant material and solicited input from key stakeholders. Inclusion/exclusion criteria were applied to select relevant material and qualitative information was charted from the selected literature.Results: A total of 10,102 articles were identified from searching the literature databases, 821 were deemed relevant to our scoping review. An additional 401 were identified from updates, website searching, references lists, key journals, and stakeholder suggestions for a total of 1,222 included articles. These were categorized and catalogued according to the inclusion criteria, and further subcategories were identified through the charting process. Topic areas represented by this review included the effectiveness of health system report cards (n = 194 articles), methodological issues in their development (n = 815 articles), stakeholder views on report cards (n = 144 articles), and ethical considerations around their development (n = 69 articles).Conclusions: The scoping review methodology has permitted us to characterize and catalogue the extensive body of literature pertaining to health system report cards. The resulting literature repository that our review has created can be of use to researchers and health system stakeholders interested in the topic of health system quality measurement and reporting. © 2010 Brien et al; licensee BioMed Central Ltd

Genome-wide and Ordered-Subset linkage analyses provide support for autism loci on 17q and 19p with evidence of phenotypic and interlocus genetic correlates

BACKGROUND: Autism is a neurobehavioral spectrum of phenotypes characterized by deficits in the development of language and social relationships and patterns of repetitive, rigid and compulsive behaviors. Twin and family studies point to a significant genetic etiology, and several groups have performed genomic linkage screens to identify susceptibility loci. METHODS: We performed a genome-wide linkage screen in 158 combined Tufts, Vanderbilt and AGRE (Autism Genetics Research Exchange) multiplex autism families using parametric and nonparametric methods with a categorical autism diagnosis to identify loci of main effect. Hypothesizing interdependence of genetic risk factors prompted us to perform exploratory studies applying the Ordered-Subset Analysis (OSA) approach using LOD scores as the trait covariate for ranking families. We employed OSA to test for interlocus correlations between loci with LOD scores ≥1.5, and empirically determined significance of linkage in optimal OSA subsets using permutation testing. Exploring phenotypic correlates as the basis for linkage increases involved comparison of mean scores for quantitative trait-based subsets of autism between optimal subsets and the remaining families. RESULTS: A genome-wide screen for autism loci identified the best evidence for linkage to 17q11.2 and 19p13, with maximum multipoint heterogeneity LOD scores of 2.9 and 2.6, respectively. Suggestive linkage (LOD scores ≥1.5) at other loci included 3p, 6q, 7q, 12p, and 16p. OSA revealed positive correlations of linkage between the 19p locus and 17q, between 19p and 6q, and between 7q and 5p. While potential phenotypic correlates for these findings were not identified for the chromosome 7/5 combination, differences indicating more rapid achievement of "developmental milestones" was apparent in the chromosome 19 OSA-defined subsets for 17q and 6q. OSA was used to test the hypothesis that 19p linkage involved more rapid achievement of these milestones and it revealed significantly increased LOD* scores at 19p13. CONCLUSIONS: Our results further support 19p13 as harboring an autism susceptibility locus, confirm other linkage findings at 17q11.2, and demonstrate the need to analyze more discreet trait-based subsets of complex phenotypes to improve ability to detect genetic effects

Mutations in the UBIAD1 Gene, Encoding a Potential Prenyltransferase, Are Causal for Schnyder Crystalline Corneal Dystrophy

Schnyder crystalline corneal dystrophy (SCCD, MIM 121800) is a rare autosomal dominant disease characterized by progressive opacification of the cornea resulting from the local accumulation of lipids, and associated in some cases with systemic dyslipidemia. Although previous studies of the genetics of SCCD have localized the defective gene to a 1.58 Mbp interval on chromosome 1p, exhaustive sequencing of positional candidate genes has thus far failed to reveal causal mutations. We have ascertained a large multigenerational family in Nova Scotia affected with SCCD in which we have confirmed linkage to the same general area of chromosome 1. Intensive fine mapping in our family revealed a 1.3 Mbp candidate interval overlapping that previously reported. Sequencing of genes in our interval led to the identification of five putative causal mutations in gene UBIAD1, in our family as well as in four other small families of various geographic origins. UBIAD1 encodes a potential prenyltransferase, and is reported to interact physically with apolipoprotein E. UBIAD1 may play a direct role in intracellular cholesterol biochemistry, or may prenylate other proteins regulating cholesterol transport and storage

A Framework For Detecting Noncoding Rare-Variant associations of Large-Scale Whole-Genome Sequencing Studies

Large-scale whole-genome sequencing studies have enabled analysis of noncoding rare-variant (RV) associations with complex human diseases and traits. Variant-set analysis is a powerful approach to study RV association. However, existing methods have limited ability in analyzing the noncoding genome. We propose a computationally efficient and robust noncoding RV association detection framework, STAARpipeline, to automatically annotate a whole-genome sequencing study and perform flexible noncoding RV association analysis, including gene-centric analysis and fixed window-based and dynamic window-based non-gene-centric analysis by incorporating variant functional annotations. In gene-centric analysis, STAARpipeline uses STAAR to group noncoding variants based on functional categories of genes and incorporate multiple functional annotations. In non-gene-centric analysis, STAARpipeline uses SCANG-STAAR to incorporate dynamic window sizes and multiple functional annotations. We apply STAARpipeline to identify noncoding RV sets associated with four lipid traits in 21,015 discovery samples from the Trans-Omics for Precision Medicine (TOPMed) program and replicate several of them in an additional 9,123 toPMed samples. We also analyze five non-lipid toPMed traits

Genetic determinants of telomere length from 109,122 ancestrally diverse whole-genome sequences in TOPMed

Genetic studies on telomere length are important for understanding age-related diseases. Prior GWAS for leukocyte TL have been limited to European and Asian populations. Here, we report the first sequencing-based association study for TL across ancestrally-diverse individuals (European, African, Asian and Hispanic/Latino) from the NHLBI Trans-Omics for Precision Medicine (TOPMed) program. We used whole genome sequencing (WGS) of whole blood for variant genotype calling and the bioinformatic estimation of telomere length in n=109,122 individuals. We identified 59 sentinel variants (p-value OBFC1indicated the independent signals colocalized with cell-type specific eQTLs for OBFC1 (STN1). Using a multi-variant gene-based approach, we identified two genes newly implicated in telomere length, DCLRE1B (SNM1B) and PARN. In PheWAS, we demonstrated our TL polygenic trait scores (PTS) were associated with increased risk of cancer-related phenotypes

Social anxiety symptoms in young children:Investigating the interplay of theory of mind and expressions of shyness

Children’s early onset of social anxiety may be associated with their social understanding, and their ability to express emotions adaptively. We examined whether social anxiety in 48-month-old children (N = 110; 54 boys) was related to: a) a lower level of theory of mind (ToM); b) a lower proclivity to express shyness in a positive way (adaptive); and c) a higher tendency to express shyness in a negative way (non-adaptive). In addition, we investigated to what extent children’s level of social anxiety was predicted by the interaction between ToM and expressions of shyness. Children’s positive and negative expressions of shyness were observed during a performance task. ToM was measured with a validated battery, and social anxiety was assessed using both parents’ reports on questionnaires. Socially anxious children had a lower level of ToM, and displayed more negative and less positive shy expressions. However, children with a lower level of ToM who expressed more positive shyness were less socially anxious. Additional results show that children who displayed shyness only in a negative manner were more socially anxious than children who expressed shyness only in a positive way and children who did not display any shyness. Moreover, children who displayed both positive and negative expressions of shyness were more socially anxious than children who displayed shyness only in a positive way. These findings highlight the importance of ToM development and socio-emotional strategies, and their interaction, on the early development of social anxiety