Citations

Abstract Introduction Genetic loci for Alzheimer's disease (AD) have been identified in whites of European ancestry, but the genetic architecture of AD among other populations is less understood. Methods We conducted a transethnic genome‐wide association study (GWAS) for late‐onset AD in Stage 1 sample including whites of European Ancestry, African‐Americans, Japanese, and Israeli‐Arabs assembled by the Alzheimer's Disease Genetics Consortium. Suggestive results from Stage 1 from novel loci were followed up using summarized results in the International Genomics Alzheimer's Project GWAS dataset. Results Genome‐wide significant (GWS) associations in single‐nucleotide polymorphism (SNP)–based tests ( P < 5 × 10 −8 ) were identified for SNPs in PFDN1/HBEGF , USP6NL/ECHDC3 , and BZRAP1‐AS1 and for the interaction of the (apolipoprotein E) APOE ε4 allele with NFIC SNP. We also obtained GWS evidence ( P < 2.7 × 10 −6 ) for gene‐based association in the total sample with a novel locus, TPBG ( P = 1.8 × 10 −6 ). Discussion Our findings highlight the value of transethnic studies for identifying novel AD susceptibility loci.

A large cohort consisting of all children born to mothers from community provides ‘natural’ selection into different exposures and is a powerful resource for epidemiological research. A large population-based birth cohort with detailed systematic information already recorded, as part of longitudinal medical care, historical and current school data, detailed birth certificate data and all three resources available for every member of the birth cohort, are extremely rare. Our population-based birth cohort consists of all children born between 1976 and 2000 to mothers residing in Olmsted County, Minnesota, at the time of child's birth (N=39 890). In this paper, we provide a comprehensive report of the method describing the identification, the characteristics and longitudinal follow-up of each child (and family members) from the birth cohort, wealth of complementary resources of data and study measures and designs (retrospective, combined retrospective/prospective). In the last decade or so, we obtained scientific and clinically needed answers for incidence rates, potential risk/protective factors, treatment, comorbidities, outcomes, cost/usage and potential biases (that are always assessed and clinically interpreted) of many developmental learning and behavioural disorders (DLBDs) including learning and attention-deficit/hyperactivity disorders, intellectual disability, speech-language impairment and autism spectrum disorder. Many current and future questions related to DLBDs are remaining to be answered. The Olmsted County Birth Cohort (OCBC) is an example of a comprehensive, contemporary epidemiological research model for the development of similar research infrastructures, and its current and future results are important for replication and comparison with other population-based retrospective and prospective birth cohort studies.

Abstract Objectives: To develop evidence-based guideline recommendations through a systematic review of the literature to establish standard molecular biomarker testing of colorectal cancer (CRC) tissues to guide epidermal growth factor receptor (EGFR) therapies and conventional chemotherapy regimens. Methods: The American Society for Clinical Pathology, College of American Pathologists, Association for Molecular Pathology, and American Society of Clinical Oncology convened an expert panel to develop an evidence-based guideline to establish standard molecular biomarker testing and guide therapies for patients with CRC. A comprehensive literature search that included more than 4,000 articles was conducted. Results: Twenty-one guideline statements were established. Conclusions: Evidence supports mutational testing for EGFR signaling pathway genes, since they provide clinically actionable information as negative predictors of benefit to anti-EGFR monoclonal antibody therapies for targeted therapy of CRC. Mutations in several of the biomarkers have clear prognostic value. Laboratory approaches to operationalize CRC molecular testing are presented.

Objectives.— To develop evidence-based guideline recommendations through a systematic review of the literature to establish standard molecular biomarker testing of colorectal cancer (CRC) tissues to guide epidermal growth factor receptor (EGFR) therapies and conventional chemotherapy regimens. Methods.— The American Society for Clinical Pathology, College of American Pathologists, Association for Molecular Pathology, and American Society of Clinical Oncology convened an expert panel to develop an evidence-based guideline to establish standard molecular biomarker testing and guide therapies for patients with CRC. A comprehensive literature search that included more than 4,000 articles was conducted. Results.— Twenty-one guideline statements were established. Conclusions.— Evidence supports mutational testing for EGFR signaling pathway genes, since they provide clinically actionable information as negative predictors of benefit to anti-EGFR monoclonal antibody therapies for targeted therapy of CRC. Mutations in several of the biomarkers have clear prognostic value. Laboratory approaches to operationalize CRC molecular testing are presented.

Purpose: We sought to assess for impact on management trends in new patients presenting to our institution with stress urinary incontinence (SUI) following the release of the FDA Health Notification in July 2011 for vaginal mesh. Materials and methods: Chart analysis was performed on patients assigned a primary International Classification of Diseases (ICD-9) diagnosis code of 625.6 for SUI at initial consultation by two providers at our institution between June 1, 2010 and November 30, 2014. Rates of treatment and types of procedures performed were analyzed: urethral bulking, mesh sling, or pubovaginal sling. Results: A total of 333 new patients were identified with an increasing trend over time. One hundred and twenty-three patients underwent 153 procedures for stress incontinence. The mean proportion that had a procedure per six-month period was 37%, with decreasing proportions over time. Initially all procedures were midurethral mesh slings, with a decline at the time of and after the notification, and a temporary increase in bulking procedures. Subsequently, there was a rise again in sling placement, namely with an increase in pubovaginal slings. Of the 20 pubovaginal slings placed, 13 were placed in patients who had a prior anti-incontinence surgery (eight for sling failure, vaginal mesh, or fixed urethra, and two in patients with mesh extrusion/erosion). Seven were performed in patients who had never had prior surgery (two for very high-grade incontinence, two with urethral diverticulectomy, and three in patients who expressed concern about mesh). Conclusions: Although there were an increasing number of patients seen for management of SUI over time, there was a progressive decrease in the proportion of patients having anti-incontinence procedures after release of the FDA notification. There was an overall decrease in the use of mesh slings and an increase in bulking, and more notably, placement of pubovaginal slings.

To examine gaps in communication versus documentation of weight-management clinical practices, communication was recorded during primary care visits with 6- to 12-year-old overweight/obese Latino children. Communication/documentation content was coded by 3 reviewers using communication transcripts and health-record documentation. Discrepancies in communication/documentation content codes were resolved through consensus. Bivariate/multivariable analyses examined factors associated with discrepancies in benchmark communication/documentation. Benchmarks were neither communicated nor documented in up to 42% of visits, and communicated but not documented or documented but not communicated in up to 20% of visits. Lowest benchmark performance rates were for laboratory studies (35%) and nutrition/weight-management referrals (42%). In multivariable analysis, overweight (vs obesity) was associated with 1.6 more discrepancies in communication versus documentation ( P = .03). Many weight-management benchmarks are not met, not documented, or performed without being communicated. Enhanced communication with families and documentation in health records may promote lifestyle changes in overweight children and higher quality care for overweight children in primary care.