Enhancing a Taxonomy for Health Information Technology: An Exploratory Study of User Input Towards Folksonomy

The U.S. Agency for Healthcare Research and Quality has created a public website to disseminate critical information regarding its health information technology initiative. The website is maintained by AHRQ's Natiomal Resource Center (NRC) for Health Information Technology. In the latest continuous quality improvement project, the NRC used the site's search logs to extract user-generated search phrases. The phrases were then compared to the site's controlled vocabulary with respect to language, grammar, and search precision. Results of the comparison demonstrate that search log data can be a cost-effective way to improve controlled vocabularies as well as information retrieval. User-entered search phrases were found to also share many similarities with folksonomy tags

Development of a Taxonomy for Health Information Technology

Taxonomies provide schemas to help classify entities and define the relationships between them. Early computing enabled the development of ontologies and Medical Subject Headings (MeSH), the first modern classification of medical terminology as applied to medical literature. Later developments, such as MEDLINE, expanded MeSH to include a number of medical informatics terms. However, a lack of specificity in MeSH and other existing informatics taxonomies for terminology used to describe the growing field of health information technology (health IT) created the need for the development of a specialized taxonomy. Experts associated with the Agency for Healthcare Research and Qualitys (AHRQs) National Resource Center for Health Information Technology (NRC) created and evaluated a taxonomy for health IT, to enable users of a public health IT Web site to efficiently identify resources within an online, searchable repository

Linking Health Information Technology to Patient Safety and Quality Outcomes: A Bibliometric Analysis and Review

Informatics for Health and Social Care is published by Informa Healthcare. Publisher's version can be found at: http://informahealthcare.com/doi/abs/10.3109/17538157.2012.678451OBJECTIVE: To assess the scholarly output of grants funded by the Agency for Healthcare Research and Quality (AHRQ) that published knowledge relevant to the impact of health information technologies on patient safety and quality of care outcomes. STUDY DESIGN: We performed a bibliometric analysis of the identified scholarly articles, their journals, and citations. In addition, we performed a qualitative review of the full-text articles and grant documents. DATA COLLECTION/EXTRACTION METHODS: Papers published by AHRQ-funded investigators were retrieved from MEDLINE, journal impact factors were extracted from the 2010 Thompson Reuters Journal Citation Report, citations were retrieved from ISI's Web of Knowledge and Google Scholar. PRINCIPAL FINDINGS: Seventy-two articles met the criteria for review. Most articles addressed one or more of AHRQ's outcome goals and focus priorities. The average impact factor for the journals was 4.005 (range: 0.654-28.899). The articles, and their respective grants, represented a broad range of health information technologies. CONCLUSIONS: This set of AHRQ-funded research projects addressed the goals and priorities of AHRQ, indicating notable contributions to the scientific knowledge base on the impact of information system use in healthcare.This work was supported, in part, by the National Resource Center of the Agency for Healthcare Research and Quality, contract number 290-04-0016

Modelling the impact of improving screening and treatment of chronic hepatitis C virus infection on future hepatocellular carcinoma rates and liver-related mortality.

BACKGROUND: The societal, clinical and economic burden imposed by the complications of chronic hepatitis C virus (HCV) infection - including cirrhosis and hepatocellular carcinoma (HCC) - is expected to increase over the coming decades. However, new therapies may improve sustained virological response (SVR) rates and shorten treatment duration. This study aimed to estimate the future burden of HCV-related disease in England if current management strategies remain the same and the impact of increasing diagnosis and treatment of HCV as new therapies become available. METHODS: A previously published model was adapted for England using published literature and government reports, and validated through an iterative process of three meetings of HCV experts. The impact of increasing diagnosis and treatment of HCV as new therapies become available was modelled and compared to the base-case scenario of continuing current management strategies. To assess the 'best case' clinical benefit of new therapies, the number of patients treated was increased by a total of 115% by 2018. RESULTS: In the base-case scenario, total viraemic (HCV RNA-positive) cases of HCV in England will decrease from 144,000 in 2013 to 76,300 in 2030. However, due to the slow progression of chronic HCV, the number of individuals with cirrhosis, decompensated cirrhosis and HCC will continue to increase over this period. The model suggests that the 'best case' substantially reduces HCV-related hepatic disease and HCV-related liver mortality by 2020 compared to the base-case scenario. The number of HCV-related HCC cases would decrease 50% by 2020 and the number progressing from infection to decompensated cirrhosis would decline by 65%. Therefore, compared to projections of current practices, increasing treatment numbers by 115% by 2018 would reduce HCV-related mortality by 50% by 2020. CONCLUSIONS: This analysis suggests that with current treatment practices the number of patients developing HCV-related cirrhosis, decompensated cirrhosis and HCC will increase substantially, with HCV-related liver deaths likely to double by 2030. However, increasing diagnosis and treatment rates could optimise the reduction in the burden of disease produced by the new therapies, potentially halving HCV-related liver mortality and HCV-related HCC by 2020

Qualitative impact assessment of land management interventions on Ecosystem Services (“QEIA”). Report 3.7: Cultural Services

The focus of this project was to provide a rapid qualitative assessment of land management interventions on Ecosystem Services (ES) proposed for inclusion in Environmental Land Management (ELM) schemes. This involved a review of the current evidence base by ten expert teams drawn from the independent research community in a consistent series of ten Evidence Reviews. These reviews were undertaken rapidly at Defra’s request and together captured more than 2000 individual sources of evidence. These reviews were then used to inform an Integrated Assessment (IA) to provide a more accessible summary of these evidence reviews with a focus on capturing the actions with the greatest potential magnitude of change for the intended ES and their potential co-benefits and trade-offs across the Ecosystem Services and Ecosystem Services Indicators. The final IA table captured scores for 741 actions across 8 Themes, 33 ES and 53 ES-indicators. This produced a total possible matrix of 39,273 scores. It should be noted that this piece of work is just one element of the wider underpinning work Defra has commissioned to support the development of the ELM schemes. The project was carried out in two phases with the environmental and provisioning services commissioned in Phase 1 and cultural and regulatory services in a follow-on Phase 2. Due to the urgency of the need for these evidence reviews, there was insufficient time for systematic reviews and therefore the reviews relied on the knowledge of the team of the peer reviewed and grey literature with some rapid additional checking of recent reports and papers. This limitation of the review process was clearly explained and understood by Defra. The review presented here is one of the ten evidence reviews which informed the IA

SMAD6 variants in craniosynostosis: genotype and phenotype evaluation

Purpose: Enrichment of heterozygous missense and truncating SMAD6 variants was previously reported in nonsyndromic sagittal and metopic synostosis, and interaction of SMAD6 variants with a common polymorphism near BMP2 (rs1884302) was proposed to contribute to inconsistent penetrance. We determined the occurrence of SMAD6 variants in all types of craniosynostosis, evaluated the impact of different missense variants on SMAD6 function, and tested independently whether rs1884302 genotype significantl

Diagnostic value of exome and whole genome sequencing in craniosynostosis

Background Craniosynostosis, the premature fusion of one or more cranial sutures, occurs in ~1 in 2250 births, either in isolation or as part of a syndrome. Mutations in at least 57 genes have been associated with craniosynostosis, but only a minority of these are included in routine laboratory genetic testing. Methods We used exome or whole genome sequencing to seek a genetic cause in a cohort of 40 subjects with craniosynostosis, selected by clinical or molecular geneticists as being high-priority cases, and in whom prior clinically driven genetic testing had been negative. Results We identified likely associated mutations in 15 patients (37.5%), involving 14 different genes. All genes were mutated in single families, except for IL11RA (two families). We classified the other positive diagnoses as follows: commonly mutated craniosynostosis genes with atypical presentation (EFNB1, TWIST1); other core craniosynostosis genes (CDC45, MSX2, ZIC1); genes for which mutations are only rarely associated with craniosynostosis (FBN1, HUWE1, KRAS, STAT3); and known disease genes for which a causal relationship with craniosynostosis is currently unknown (AHDC1, NTRK2). In two further families, likely novel disease genes are currently undergoing functional validation. In 5 of the 15 positive cases, the (previously unanticipated) molecular diagnosis had immediate, actionable consequences for either genetic or medical management (mutations in EFNB1, FBN1, KRAS, NTRK2, STAT3). Conclusions This substantial genetic heterogeneity, and the multiple actionable mutations identified, emphasises the benefits of exome/whole genome sequencing to identify causal mutations in craniosynostosis cases for which routine clinical testing has yielded negative results

Pathogenic variants in the paired-related homeobox 1 gene (PRRX1) cause craniosynostosis with incomplete penetrance

Purpose Studies previously implicated PRRX1 in craniofacial development, including demonstration of murine Prrx1 expression in the pre-osteogenic cells of the cranial sutures. We investigated the role of heterozygous missense and loss-of-function variants in PRRX1 associated with craniosynostosis. Methods Trio-based genome, exome or targeted sequencing were used to screen PRRX1 in patients with craniosynostosis; immunofluorescence analyses were used to assess nuclear localization of wild-type and mutant proteins. Results Genome sequencing identified 2 of 9 sporadically affected individuals with syndromic/multisuture craniosynostosis who were heterozygous for rare/undescribed variants in PRRX1. Exome or targeted sequencing of PRRX1 revealed a further 9/1449 patients with craniosynostosis harboring deletions or rare heterozygous variants within the homeodomain. By collaboration, seven additional individuals (four families) were identified with putatively pathogenic PRRX1 variants. Immunofluorescence analyses showed that missense variants within the PRRX1 homeodomain cause abnormal nuclear localization. Of patients with variants considered likely pathogenic, bicoronal or other multi-suture synostosis was present in 11/17 (65% of the cases). Pathogenic variants were inherited from unaffected relatives in many instances, yielding a 12.5% penetrance estimate for craniosynostosis. Conclusion This work supports a key role for PRRX1 in cranial suture development and shows that haploinsufficiency of PRRX1 is a relatively frequent cause of craniosynostosis

First Phase 1 Double-Blind, Placebo-Controlled, Randomized Rectal Microbicide Trial Using UC781 Gel with a Novel Index of Ex Vivo Efficacy

Objectives: Successful control of the HIV/AIDS pandemic requires reduction of HIV-1 transmission at sexually-exposed mucosae. No prevention studies of the higher-risk rectal compartment exist. We report the first-in-field Phase 1 trial of a rectally-applied, vaginally-formulated microbicide gel with the RT-inhibitor UC781 measuring clinical and mucosal safety, acceptability and plasma drug levels. A first-in-Phase 1 assessment of preliminary pharmacodynamics was included by measuring changes in ex vivo HIV-1 suppression in rectal biopsy tissue after exposure to product in vivo. Methods: HIV-1 seronegative, sexually-abstinent men and women (N = 36) were randomized in a double-blind, placebo-controlled trial comparing UC781 gel at two concentrations (0.1%, 0.25%) with placebo gel (1:1:1). Baseline, single-dose exposure and a separate, 7-day at-home dosing were assessed. Safety and acceptability were primary endpoints. Changes in colorectal mucosal markers and UC781 plasma drug levels were secondary endpoints; ex vivo biopsy infectibility was an ancillary endpoint. Results: All 36 subjects enrolled completed the 7-14 week trial (100% retention) including 3 flexible sigmoidoscopies, each with 28 biopsies (14 at 10 cm; 14 at 30 cm). There were 81 Grade 1 adverse events (AEs) and 8 Grade 2; no Grade 3, 4 or procedure-related AEs were reported. Acceptability was high, including likelihood of future use. No changes in mucosal immunoinflammatory markers were identified. Plasma levels of UC781 were not detected. Ex vivo infection of biopsies using two titers of HIV-1 BaL showed marked suppression of p24 in tissues exposed in vivo to 0.25% UC781; strong trends of suppression were seen with the lower 0.1% UC781 concentration. Conclusions: Single and 7-day topical rectal exposure to both concentrations of UC781 were safe with no significant AEs, high acceptability, no detected plasma drug levels and no significant mucosal changes. Ex vivo biopsy infections demonstrated marked suppression of HIV infectibility, identifying a potential early biomarker of efficacy. (Registered at ClinicalTrials.gov; #NCT00408538). © 2011 Anton et al