Bridging data models and terminologies to support adverse drug event reporting using EHR data.

INTRODUCTION: This article is part of the Focus Theme of METHODs of Information in Medicine on "Managing Interoperability and Complexity in Health Systems". BACKGROUND: SALUS project aims at building an interoperability platform and a dedicated toolkit to enable secondary use of electronic health records (EHR) data for post marketing drug surveillance. An important component of this toolkit is a drug-related adverse events (AE) reporting system designed to facilitate and accelerate the reporting process using automatic prepopulation mechanisms. OBJECTIVE: To demonstrate SALUS approach for establishing syntactic and semantic interoperability for AE reporting. METHOD: Standard (e.g. HL7 CDA-CCD) and proprietary EHR data models are mapped to the E2B(R2) data model via SALUS Common Information Model. Terminology mapping and terminology reasoning services are designed to ensure the automatic conversion of source EHR terminologies (e.g. ICD-9-CM, ICD-10, LOINC or SNOMED-CT) to the target terminology MedDRA which is expected in AE reporting forms. A validated set of terminology mappings is used to ensure the reliability of the reasoning mechanisms. RESULTS: The percentage of data elements of a standard E2B report that can be completed automatically has been estimated for two pilot sites. In the best scenario (i.e. the available fields in the EHR have actually been filled), only 36% (pilot site 1) and 38% (pilot site 2) of E2B data elements remain to be filled manually. In addition, most of these data elements shall not be filled in each report. CONCLUSION: SALUS platform's interoperability solutions enable partial automation of the AE reporting process, which could contribute to improve current spontaneous reporting practices and reduce under-reporting, which is currently one major obstacle in the process of acquisition of pharmacovigilance data.

Reasons (not) to Spend a Few Billions More on EHRs: How Human Factors Research Can Help.

OBJECTIVES: To select best medical informatics research works published in 2013 on electronic health record (EHR) adoption, design, and impact, from the perspective of human factors and organizational issues (HFOI). METHODS: We selected 2,764 papers by querying PubMed (Mesh and TIAB) as well as using a manual search. Papers were evaluated based on pre-defined exclusion and inclusion criteria from their title, keywords, and abstract to select 15 candidate best papers, finally reviewed by 4 external reviewers using a standard evaluation grid. RESULTS: Five papers were selected as best papers to illustrate how human factors approaches can improve EHR adoption and design. Among other contributions, these works: (i) make use of the observational and analysis methodologies of social and cognitive sciences to understand clinicians' attitudes towards EHRs, EHR use patterns, and impact on care processes, workflows, information exchange, and coordination of care; (ii) take into account macro- (environmental) and meso- (organizational) level factors to analyze EHR adoption or lack thereof; (iii) highlight the need for qualitative studies to analyze the unexpected side effects of EHRs on cognitive and work processes as well as the persistent use of paper. CONCLUSION: Selected papers tend to demonstrate that HFOI approaches and methodologies are essential to bridge the gap between EHR systems and end users, and to reduce regularly reported adoption failures and unexpected consequences.

Why Medical Informatics (still) Needs Cognitive and Social Sciences.

OBJECTIVES: To summarize current excellent medical informatics research in the field of human factors and organizational issues. METHODS: Using PubMed, a total of 3,024 papers were selected from 17 journals. The papers were evaluated on the basis of their title, keywords, and abstract, using several exclusion and inclusion criteria. 15 preselected papers were carefully evaluated by six referees using a standard evaluation grid. RESULTS: Six best papers were selected exemplifying the central role cognitive and social sciences can play in medical informatics research. Among other contributions, those studies: (i) make use of the distributed cognition paradigm to model and understand clinical care situations; (ii) take into account organizational issues to analyse the impact of HIT on information exchange and coordination processes; (iii) illustrate how models and empirical data from cognitive psychology can be used in medical informatics; and (iv) highlight the need of qualitative studies to analyze the unexpected side effects of HIT on cognitive and work processes. CONCLUSION: The selected papers demonstrate that paradigms, methodologies, models, and results from cognitive and social sciences can help to bridge the gap between HIT and end users, and contribute to limit adoption failures that are reported regularly.

HopX1 in Erwinia amylovora functions as an avirulence protein in apple and is regulated by HrpL.

Fire blight is a devastating disease of rosaceous plants caused by the Gram-negative bacterium Erwinia amylovora. This pathogen delivers virulence proteins into host cells utilizing the type III secretion system (T3SS). Expression of the T3SS and of translocated and secreted substrates is activated by the alternative sigma factor HrpL, which recognizes hrp box promoters upstream of regulated genes. A collection of hidden Markov model (HMM) profiles was used to identify putative hrp boxes in the genome sequence of Ea273, a highly virulent strain of E. amylovora. Among potential virulence factors preceded by putative hrp boxes, two genes previously known as Eop3 and Eop2 were characterized. The presence of functionally active hrp boxes upstream of these two genes was confirmed by ß-glucuronidase (GUS) assays. Deletion mutants of the latter candidate genes, renamed hopX1(Ea) and hopAK1(Ea), respectively, did not differ in virulence from the wild-type strain when assayed in pear fruit and apple shoots. The hopX1(Ea) deletion mutant of Ea273, complemented with a plasmid overexpressing hopX1(E)(a), suppressed the development of the hypersensitivity response (HR) when inoculated into Nicotiana benthamiana; however, it contributed to HR in Nicotiana tabacum and significantly reduced the progress of disease in apple shoots, suggesting that HopX1(Ea) may act as an avirulence protein in apple shoots.

Complete genome sequence of the plant pathogen Erwinia amylovora strain ATCC 49946.

Erwinia amylovora causes the economically important disease fire blight that affects rosaceous plants, especially pear and apple. Here we report the complete genome sequence and annotation of strain ATCC 49946. The analysis of the sequence and its comparison with sequenced genomes of closely related enterobacteria revealed signs of pathoadaptation to rosaceous hosts.

Computational and experimental analysis of microsatellites in rice (Oryza sativa L.): frequency, length variation, transposon associations, and genetic marker potential.

A total of 57.8 Mb of publicly available rice (Oryza sativa L.) DNA sequence was searched to determine the frequency and distribution of different simple sequence repeats (SSRs) in the genome. SSR loci were categorized into two groups based on the length of the repeat motif. Class I, or hypervariable markers, consisted of SSRs > or =20 bp, and Class II, or potentially variable markers, consisted of SSRs > or =12 bp <20 bp. The occurrence of Class I SSRs in end-sequences of EcoRI- and HindIII-digested BAC clones was one SSR per 40 Kb, whereas in continuous genomic sequence (represented by 27 fully sequenced BAC and PAC clones), the frequency was one SSR every 16 kb. Class II SSRs were estimated to occur every 3.7 kb in BAC ends and every 1.9 kb in fully sequenced BAC and PAC clones. GC-rich trinucleotide repeats (TNRs) were most abundant in protein-coding portions of ESTs and in fully sequenced BACs and PACs, whereas AT-rich TNRs showed no such preference, and di- and tetranucleotide repeats were most frequently found in noncoding, intergenic regions of the rice genome. Microsatellites with poly(AT)n repeats represented the most abundant and polymorphic class of SSRs but were frequently associated with the Micropon family of miniature inverted-repeat transposable elements (MITEs) and were difficult to amplify. A set of 200 Class I SSR markers was developed and integrated into the existing microsatellite map of rice, providing immediate links between the genetic, physical, and sequence-based maps. This contribution brings the number of microsatellite markers that have been rigorously evaluated for amplification, map position, and allelic diversity in Oryza spp. to a total of 500.

Evaluation of short-term nonpharmacological treatment of insomnia in a clinical setting.

Of the 86 chronic insomnia patients we treated with nonpharmacological means, 74 improved considerably. The subjective improvement was confirmed by the outcome of the sleep logs registered after 4 weeks of treatment (decrease in sleep-onset latency, wake after sleep onset, and an increase of sleep efficiency). Of the 49 patients who had used hypnotics at intake, 18 discontinued their medication and 19 considerably reduced theirs after therapy. The investigated population was characterized by high scores for anxiety, depression, and somaticization; the depression and anxiety scores were significantly higher for the hypnotics users. The percentage of nonresponders (patients who were unaffected by the treatment) was highest for the group of homemakers and for the group of patients with a low level of education. Significantly less of the nonresponders had received cognitive therapy compared with responders. The value of nonpharmacological treatment lies in the fact that it leads to a subjective improvement of sleep and to increased control over the sleep problem that the patient was experiencing. Helping the patients to obtain control over their sleep problems was our main therapeutic goal.

Hypnotics. Drug selection by means of the System of Objectified Judgement Analysis (SOJA) method.

Selection of hypnotics for drug formularies in The Netherlands, France and the UK is made by means of the System of Objectified Judgement Analysis (SOJA) method. The following criteria are included in the method: clinical efficacy (maximal 300 points), adverse effects (250 points), clinical documentation (150 points), cost (120 points), pharmacokinetic properties (80 points), toxicity (50 points), drug interactions (30 points) and the number of tablet strengths available (20 points). In all 3 countries, zolpidem, zopiclone and temazepam showed the highest score, followed by lormetazepam. High scores favour inclusion in formularies. Nitrazepam and loprazolam scored 75 to 130 points less than the top 3, and flunitrazepam shows the lowest score (119 to 183 points less than zolpidem, zopiclone and temazepam). Therefore, the first 3 (or 4) hypnotics are most suitable for formulary inclusion while the others are not.

Chondromyxoid fibroma in the metacarpal bone of the thumb.

We present a case of a chondromyxoid fibroma in the exceptionally rare location of the first metacarpal bone in a 12-year-old boy. The tumor had evolved asymptomatically over a period of 8 years destroying all diaphyseal trabecular bone. No recurrence was evident 50 months following aggressive curettage of the metacarpal lesion, which presented a predominantly myxoid appearance.

Tumoral calcinosis.

Tumoral calcinosis is an uncommon, usually solitary, tumour-like mass characterized by soft tissue calcification for no apparent reason. Nearly all cases have occurred in negroes, including 2 previously recorded in this country. We report 7 cases seen over a period of 3 years in English caucasian patients and suggest that the condition is not rare but goes unrecognized under a variety of guises. Three of these 7 patients, 2 of whom were on haemodialysis for renal failure, had isolated hyperphosphataemia, which is the only aetiological factor detected so far. Surgical excision appears to be the only effective treatment.