Mixed-method study of a conceptual model of evidence-based intervention sustainment across multiple public-sector service settings.

BackgroundThis study examines sustainment of an EBI implemented in 11 United States service systems across two states, and delivered in 87 counties. The aims are to 1) determine the impact of state and county policies and contracting on EBI provision and sustainment; 2) investigate the role of public, private, and academic relationships and collaboration in long-term EBI sustainment; 3) assess organizational and provider factors that affect EBI reach/penetration, fidelity, and organizational sustainment climate; and 4) integrate findings through a collaborative process involving the investigative team, consultants, and system and community-based organization (CBO) stakeholders in order to further develop and refine a conceptual model of sustainment to guide future research and provide a resource for service systems to prepare for sustainment as the ultimate goal of the implementation process.MethodsA mixed-method prospective and retrospective design will be used. Semi-structured individual and group interviews will be used to collect information regarding influences on EBI sustainment including policies, attitudes, and practices; organizational factors and external policies affecting model implementation; involvement of or collaboration with other stakeholders; and outer- and inner-contextual supports that facilitate ongoing EBI sustainment. Document review (e.g., legislation, executive orders, regulations, monitoring data, annual reports, agendas and meeting minutes) will be used to examine the roles of state, county, and local policies in EBI sustainment. Quantitative measures will be collected via administrative data and web surveys to assess EBI reach/penetration, staff turnover, EBI model fidelity, organizational culture and climate, work attitudes, implementation leadership, sustainment climate, attitudes toward EBIs, program sustainment, and level of institutionalization. Hierarchical linear modeling will be used for quantitative analyses. Qualitative analyses will be tailored to each of the qualitative methods (e.g., document review, interviews). Qualitative and quantitative approaches will be integrated through an inclusive process that values stakeholder perspectives.DiscussionThe study of sustainment is critical to capitalizing on and benefiting from the time and fiscal investments in EBI implementation. Sustainment is also critical to realizing broad public health impact of EBI implementation. The present study takes a comprehensive mixed-method approach to understanding sustainment and refining a conceptual model of sustainment

The Sex and Race Specific Relationship between Anthropometry and Body Fat Composition Determined from Computed Tomography: Evidence from the Multi-Ethnic Study of Atherosclerosis.

BackgroundFew studies have investigated the relationship of anthropometric measurements with computed tomography (CT) body fat composition, and even fewer determined if these relationships differ by sex and race.MethodsCT scans from 1,851 participants in the population based Multi-Ethnic Study of Atherosclerosis were assessed for visceral and subcutaneous fat areas by semi-automated segmentation of body compartments. Regression models were used to investigate relationships for anthropometry with visceral and subcutaneous fat separately by sex and race/ethnicity.ResultsParticipants were 50% female, 41% Caucasian, 13% Asian, 21% African American, and 25% Hispanic. For visceral fat, the positive relationship with weight (p = 0.028), waist circumference (p<0.001), waist to hip ratio (p<0.001), and waist to height ratio (p = 0.05) differed by sex, with a steeper slope for men. That is, across the range of these anthropometric measures the rise in visceral fat is faster for men than for women. Additionally, there were differences by race/ethnicity in the relationship with height (p<0.001), weight (p<0.001), waist circumference (p<0.001), hip circumference (p = 0.006), and waist to hip ratio (p = 0.001) with the Hispanic group having shallower slopes. For subcutaneous fat, interaction by sex was found for all anthropometric indices at p<0.05, but not for race/ethnicity.ConclusionThe relationship between anthropometry and underlying adiposity differs by sex and race/ethnicity. When anthropometry is used as a proxy for visceral fat in research, sex-specific models should be used

Dynamic Adaptation Process to Implement an Evidence-based Child Maltreatment Intervention

Background: Adaptations are often made to evidence-based practices (EBPs) by systems, organizations, and/or service providers in the implementation process. The degree to which core elements of an EBP can be maintained while allowing for local adaptation is unclear. In addition, adaptations may also be needed at the system, policy, or organizational levels to facilitate EBP implementation and sustainment. This paper describes a study of the feasibility and acceptability of an implementation approach, the Dynamic Adaptation Process (DAP), designed to allow for EBP adaptation and system and organizational adaptations in a planned and considered, rather than ad hoc, way. The DAP involves identifying core elements and adaptable characteristics of an EBP, then supporting implementation with specific training on allowable adaptations to the model, fidelity monitoring and support, and identifying the need for and solutions to system and organizational adaptations. In addition, this study addresses a secondary concern, that of improving EBP model fidelity assessment and feedback in real-world settings. Methods: This project examines the feasibility, acceptability, and utility of the DAP; tests the degree to which fidelity can be maintained using the DAP compared to implementation as usual (IAU); and examines the feasibility of using automated phone or internet-enabled, computer-based technology to assess intervention fidelity and client satisfaction. The study design incorporates mixed methods in order to describe processes and factors associated with variations in both how the DAP itself is implemented and how the DAP impacts fidelity, drift, and adaptation. The DAP model is to be examined by assigning six regions in California (USA) to either the DAP (n = 3) or IAU (n = 3) to implement an EBP to prevent child neglect. Discussion: The DAP represents a data-informed, collaborative, multiple stakeholder approach to maintain intervention fidelity during the implementation of EBPs in the field by providing support for intervention, system, and organizational adaptation and intervention fidelity to meet local needs. This study is designed to address the real-world implications of EBP implementation in public sector service systems and is relevant for national, state, and local service systems and organizations

Deep coverage whole genome sequences and plasma lipoprotein(a) in individuals of European and African ancestries.

Lipoprotein(a), Lp(a), is a modified low-density lipoprotein particle that contains apolipoprotein(a), encoded by LPA, and is a highly heritable, causal risk factor for cardiovascular diseases that varies in concentrations across ancestries. Here, we use deep-coverage whole genome sequencing in 8392 individuals of European and African ancestry to discover and interpret both single-nucleotide variants and copy number (CN) variation associated with Lp(a). We observe that genetic determinants between Europeans and Africans have several unique determinants. The common variant rs12740374 associated with Lp(a) cholesterol is an eQTL for SORT1 and independent of LDL cholesterol. Observed associations of aggregates of rare non-coding variants are largely explained by LPA structural variation, namely the LPA kringle IV 2 (KIV2)-CN. Finally, we find that LPA risk genotypes confer greater relative risk for incident atherosclerotic cardiovascular diseases compared to directly measured Lp(a), and are significantly associated with measures of subclinical atherosclerosis in African Americans

Publisher Correction: Deep coverage whole genome sequences and plasma lipoprotein(a) in individuals of European and African ancestries.

The original version of this article contained an error in the name of the author Ramachandran S. Vasan, which was incorrectly given as Vasan S. Ramachandran. This has now been corrected in both the PDF and HTML versions of the article

Deep-coverage whole genome sequences and blood lipids among 16,324 individuals.

Large-scale deep-coverage whole-genome sequencing (WGS) is now feasible and offers potential advantages for locus discovery. We perform WGS in 16,324 participants from four ancestries at mean depth >29X and analyze genotypes with four quantitative traits-plasma total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, and triglycerides. Common variant association yields known loci except for few variants previously poorly imputed. Rare coding variant association yields known Mendelian dyslipidemia genes but rare non-coding variant association detects no signals. A high 2M-SNP LDL-C polygenic score (top 5th percentile) confers similar effect size to a monogenic mutation (~30 mg/dl higher for each); however, among those with severe hypercholesterolemia, 23% have a high polygenic score and only 2% carry a monogenic mutation. At these sample sizes and for these phenotypes, the incremental value of WGS for discovery is limited but WGS permits simultaneous assessment of monogenic and polygenic models to severe hypercholesterolemia

Evidence-based clinical practice guideline for the use of pit-and-fissure sealants

AbstractBackgroundThis article presents evidence-based clinical recommendations for the use of pit-and-fissure sealants on the occlusal surfaces of primary and permanent molars in children and adolescents. A guideline panel convened by the American Dental Association (ADA) Council on Scientific Affairs and the American Academy of Pediatric Dentistry conducted a systematic review and formulated recommendations to address clinical questions in relation to the efficacy, retention, and potential side effects of sealants to prevent dental caries; their efficacy compared with fluoride varnishes; and a head-to-head comparison of the different types of sealant material used to prevent caries on pits and fissures of occlusal surfaces.Types of Studies ReviewedThis is an update of the ADA 2008 recommendations on the use of pit-and-fissure sealants on the occlusal surfaces of primary and permanent molars. The authors conducted a systematic search in MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and other sources to identify randomized controlled trials reporting on the effect of sealants (available on the US market) when applied to the occlusal surfaces of primary and permanent molars. The authors used the Grading of Recommendations Assessment, Development, and Evaluation approach to assess the quality of the evidence and to move from the evidence to the decisions.ResultsThe guideline panel formulated 3 main recommendations. They concluded that sealants are effective in preventing and arresting pit-and-fissure occlusal carious lesions of primary and permanent molars in children and adolescents compared with the nonuse of sealants or use of fluoride varnishes. They also concluded that sealants could minimize the progression of noncavitated occlusal carious lesions (also referred to as initial lesions) that receive a sealant. Finally, based on the available limited evidence, the panel was unable to provide specific recommendations on the relative merits of 1 type of sealant material over the others.Conclusions and Practical ImplicationsThese recommendations are designed to inform practitioners during the clinical decision-making process in relation to the prevention of occlusal carious lesions in children and adolescents. Clinicians are encouraged to discuss the information in this guideline with patients or the parents of patients. The authors recommend that clinicians reorient their efforts toward increasing the use of sealants on the occlusal surfaces of primary and permanent molars in children and adolescents

Sealants for preventing and arresting pit-and-fissure occlusal caries in primary and permanent molars

AbstractBackgroundNational Health and Nutrition Examination Survey 2011-2012 data indicated that, in the United States, nearly one-fourth of children and over one-half of adolescents experienced dental caries in their permanent teeth. The purpose of this review was to summarize the available clinical evidence regarding the effect of dental sealants for the prevention and management of pit-and-fissure occlusal carious lesions in primary and permanent molars, compared with a control without sealants, with fluoride varnishes, or with other head-to head comparisons.Type of Studies ReviewedThe authors included parallel and split-mouth randomized controlled trials that included at least 2 years of follow-up, which they identified using MEDLINE (via PubMed), Embase, LILACS, the Cochrane Central Register of Controlled Trials, and registers of ongoing trials. Pairs of reviewers independently conducted the selection of studies, data extraction, risk of bias assessments, and quality of the evidence assessments by using the Grading of Recommendations Assessment, Development and Evaluation approach.ResultsOf 2,869 records screened, the authors determined that 24 articles (representing 23 studies) proved eligible. Moderate-quality evidence suggested that participants who received sealants had a reduced risk of developing carious lesions in occlusal surfaces of permanent molars compared with those who did not receive sealants (odds ratio [OR], 0.15; 95% confidence interval [CI], 0.08-0.27) after 7 or more years of follow-up. When the authors compared studies whose investigators had compared sealants with fluoride varnishes, they found that sealants reduced the incidence of carious lesions after 7 or more years of follow-up (OR, 0.19; 95% CI, 0.07-0.51); however, this finding was supported by low-quality evidence. On the basis of the evidence, the authors could not provide a hierarchy of effectiveness among the studies whose investigators had conducted head-to-head comparisons. The investigators of 2 trials provided information about adverse events, but they did not report any adverse events.Conclusions and Practical ImplicationsAvailable evidence suggests that sealants are effective and safe to prevent or arrest the progression of noncavitated carious lesions compared with a control without sealants or fluoride varnishes. Further research is needed to provide information about the relative merits of the different types of sealant materials

Polygenic Prediction of Weight and Obesity Trajectories from Birth to Adulthood

Severe obesity is a rapidly growing global health threat. Although often attributed to unhealthy lifestyle choices or environmental factors, obesity is known to be heritable and highly polygenic; the majority of inherited susceptibility is related to the cumulative effect of many common DNA variants. Here we derive and validate a new polygenic predictor comprised of 2.1 million common variants to quantify this susceptibility and test this predictor in more than 300,000 individuals ranging from middle age to birth. Among middle-aged adults, we observe a 13-kg gradient in weight and a 25-fold gradient in risk of severe obesity across polygenic score deciles. In a longitudinal birth cohort, we note minimal differences in birthweight across score deciles, but a significant gradient emerged in early childhood and reached 12 kg by 18 years of age. This new approach to quantify inherited susceptibility to obesity affords new opportunities for clinical prevention and mechanistic assessment. © 2019 Author(s)National Human Genome Research Institute (1K08HG0101)Wellcome Trust (202802/Z/16/Z)University of Bristol NIHR Biomedical Research Centre (S- BRC-1215-20011)National Human Genome Research Institute (HG008895)National Heart, Lung, and Blood Institute (NHLBI) HHSN268201300025CNational Heart, Lung, and Blood Institute (NHLBI) HHSN268201300026CNational Heart, Lung, and Blood Institute (NHLBI) HHSN268201300027CNational Heart, Lung, and Blood Institute (NHLBI) HHSN268201300028CNational Heart, Lung, and Blood Institute (NHLBI) HHSN268201300029CNational Heart, Lung, and Blood Institute (NHLBI) HHSN268200900041CNational Institute on Aging (AG0005)NHLBI (AG0005)National Human Genome Research Institute (U01-HG004729)National Human Genome Research Institute (U01-HG04424)National Human Genome Research Institute (U01-HG004446)Wellcome (102215/2/13/2

Transcriptional and Cellular Diversity of the Human Heart

Background: The human heart requires a complex ensemble of specialized cell types to perform its essential function. A greater knowledge of the intricate cellular milieu of the heart is critical to increase our understanding of cardiac homeostasis and pathology. As recent advances in low-input RNA sequencing have allowed definitions of cellular transcriptomes at single-cell resolution at scale, we have applied these approaches to assess the cellular and transcriptional diversity of the nonfailing human heart. Methods: Microfluidic encapsulation and barcoding was used to perform single nuclear RNA sequencing with samples from 7 human donors, selected for their absence of overt cardiac disease. Individual nuclear transcriptomes were then clustered based on transcriptional profiles of highly variable genes. These clusters were used as the basis for between-chamber and between-sex differential gene expression analyses and intersection with genetic and pharmacologic data. Results: We sequenced the transcriptomes of 287 269 single cardiac nuclei, revealing 9 major cell types and 20 subclusters of cell types within the human heart. Cellular subclasses include 2 distinct groups of resident macrophages, 4 endothelial subtypes, and 2 fibroblast subsets. Comparisons of cellular transcriptomes by cardiac chamber or sex reveal diversity not only in cardiomyocyte transcriptional programs but also in subtypes involved in extracellular matrix remodeling and vascularization. Using genetic association data, we identified strong enrichment for the role of cell subtypes in cardiac traits and diseases. Intersection of our data set with genes on cardiac clinical testing panels and the druggable genome reveals striking patterns of cellular specificity. Conclusions: Using large-scale single nuclei RNA sequencing, we defined the transcriptional and cellular diversity in the normal human heart. Our identification of discrete cell subtypes and differentially expressed genes within the heart will ultimately facilitate the development of new therapeutics for cardiovascular diseases