Fibromyalgia Syndrome Care of Iraq- and Afghanistan-Deployed Veterans in Veterans Health Administration

Little is known regarding fibromyalgia syndrome (FMS) care among Operation Iraqi Freedom/Operation Enduring Freedom/Operation New Dawn (OIF/OEF/OND) Veterans. Current recommendations include interdisciplinary, teambased combined care approaches and limited opioid use. In this study of OIF/OEF/OND Veterans who accessed Veterans Health Administration services between 2002 and 2012, we hypothesized that combined care (defined as at least 4 primary care visits/yr with visits to mental health and/or rheumatology) versus/yr only would be associated with lower risk of at least 2 opioid prescriptions 12 mo following an FMS diagnosis. Using generalized linear models with a loglink, the Poisson family, and robust standard errors, we estimated risk ratios (RRs) and 95% confidence intervals (CIs). We found that 1% of Veterans had at least 2 FMS diagnoses (International Classification of Diseases-9th Revision-Clinical Modification code 729.1) or at least 1 FMS diagnosis by rheumatology. Veterans with (vs without) FMS were more likely to be female, older, Hispanic, and never/currently married. Combined primary, mental health, and rheumatology care was associated with at least 2 opioid prescriptions (RR [95% CI] for males 2.2 [1.1–4.4] and females 2.8 [0.4–18.6]). Also, combined care was associated with at least 2 nonopioid painrelated prescriptions, a practice supported by evidence-based clinical practice guidelines. In tandem, these results provide mixed evidence of benefit of combined care for FMS. Future studies of healthcare encounter characteristics, care coordination, and benefits for Veterans with FMS are needed

Developing a manually annotated clinical document corpus to identify phenotypic information for inflammatory bowel disease

<p>Abstract</p> <p>Background</p> <p>Natural Language Processing (NLP) systems can be used for specific Information Extraction (IE) tasks such as extracting phenotypic data from the electronic medical record (EMR). These data are useful for translational research and are often found only in free text clinical notes. A key required step for IE is the manual annotation of clinical corpora and the creation of a reference standard for (1) training and validation tasks and (2) to focus and clarify NLP system requirements. These tasks are time consuming, expensive, and require considerable effort on the part of human reviewers.</p> <p>Methods</p> <p>Using a set of clinical documents from the VA EMR for a particular use case of interest we identify specific challenges and present several opportunities for annotation tasks. We demonstrate specific methods using an open source annotation tool, a customized annotation schema, and a corpus of clinical documents for patients known to have a diagnosis of Inflammatory Bowel Disease (IBD). We report clinician annotator agreement at the document, concept, and concept attribute level. We estimate concept yield in terms of annotated concepts within specific note sections and document types.</p> <p>Results</p> <p>Annotator agreement at the document level for documents that contained concepts of interest for IBD using estimated Kappa statistic (95% CI) was very high at 0.87 (0.82, 0.93). At the concept level, F-measure ranged from 0.61 to 0.83. However, agreement varied greatly at the specific concept attribute level. For this particular use case (IBD), clinical documents producing the highest concept yield per document included GI clinic notes and primary care notes. Within the various types of notes, the highest concept yield was in sections representing patient assessment and history of presenting illness. Ancillary service documents and family history and plan note sections produced the lowest concept yield.</p> <p>Conclusion</p> <p>Challenges include defining and building appropriate annotation schemas, adequately training clinician annotators, and determining the appropriate level of information to be annotated. Opportunities include narrowing the focus of information extraction to use case specific note types and sections, especially in cases where NLP systems will be used to extract information from large repositories of electronic clinical note documents.</p

Comprehensive In&nbsp;Vivo Interrogation Reveals Phenotypic Impact of Human Enhancer Variants

Establishing causal links between non-coding variants and human phenotypes is an increasing challenge. Here, we introduce a high-throughput mouse reporter assay for assessing the pathogenic potential of human enhancer variants in&nbsp;vivo and examine nearly a thousand variants in an enhancer repeatedly linked to polydactyly. We show that 71% of all rare non-coding variants previously proposed as causal lead to reporter gene expression in a pattern consistent with their pathogenic role. Variants observed to alter enhancer activity were further confirmed to cause polydactyly in knockin mice. We also used combinatorial and single-nucleotide mutagenesis to evaluate the in&nbsp;vivo impact of mutations affecting all positions of the enhancer and identified additional functional substitutions, including potentially pathogenic variants hitherto not observed in humans. Our&nbsp;results uncover the functional consequences of hundreds of mutations in a phenotype-associated enhancer and establish a widely applicable strategy for systematic in&nbsp;vivo evaluation of human enhancer variants

Implications of the Plastid Genome Sequence of Typha (Typhaceae, Poales) for Understanding Genome Evolution in Poaceae

Plastid genomes of the grasses (Poaceae) are unusual in their organization and rates of sequence evolution. There has been a recent surge in the availability of grass plastid genome sequences, but a comprehensive comparative analysis of genome evolution has not been performed that includes any related families in the Poales. We report on the plastid genome of Typha latifolia, the first non-grass Poales sequenced to date, and we present comparisons of genome organization and sequence evolution within Poales. Our results confirm that grass plastid genomes exhibit acceleration in both genomic rearrangements and nucleotide substitutions. Poaceae have multiple structural rearrangements, including three inversions, three genes losses (accD, ycf1, ycf2), intron losses in two genes (clpP, rpoC1), and expansion of the inverted repeat (IR) into both large and small single-copy regions. These rearrangements are restricted to the Poaceae, and IR expansion into the small single-copy region correlates with the phylogeny of the family. Comparisons of 73 protein-coding genes for 47 angiosperms including nine Poaceae genera confirm that the branch leading to Poaceae has significantly accelerated rates of change relative to other monocots and angiosperms. Furthermore, rates of sequence evolution within grasses are lower, indicating a deceleration during diversification of the family. Overall there is a strong correlation between accelerated rates of genomic rearrangements and nucleotide substitutions in Poaceae, a phenomenon that has been noted recently throughout angiosperms. The cause of the correlation is unknown, but faulty DNA repair has been suggested in other systems including bacterial and animal mitochondrial genomes

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Evaluating the relevance and clarity of the heart failure eMeasure implementation toolkit by using a webbased survey instrument

Background: The impact on workfl ow is an important component in determining whether an HIT implementation will be successful. Workfl ow is, unfortunately, a concept that is often ignored when implementing HIT and the literature about workfl ow in domains of quality improvement, system implementation, and process improvement has not been adequate. HIT is not always designed to fi t the workfl ow of a given organization, making it diffi cult to truly assess HIT impact on outcomes or processes.</p