As interruptions have been well studied in other domains, the authors undertook a systematic review of experimental studies in psychology and human–computer interaction to identify the task types and variables influencing interruption effects.

63 studies were identified from 812 articles retrieved by systematic searches. On the basis of interruption profiles for generic tasks, it was found that clinical tasks can be distinguished into three broad types: procedural, problem-solving, and decision-making. Twelve experimental variables that influence interruption effects were identified. Of these, six are the most important, based on the number of studies and because of their centrality to interruption effects, including working memory load, interruption position, similarity, modality, handling strategies, and practice effect. The variables are explained by three main theoretical frameworks: the activation-based goal memory model, prospective memory, and multiple resource theory.

This review provides a useful starting point for a more comprehensive examination of interruptions potentially leading to an improved understanding about the impact of this phenomenon on patient safety and task efficiency. The authors provide some recommendations to counter interruption effects.

The effects of interruption are the outcome of a complex set of variables and should not be considered as uniformly predictable or bad. The task types, variables, and theories should help us better to identify which clinical tasks and contexts are most susceptible and assist in the design of information systems and processes that are resilient to interruption.

A systematic search was conducted of the Medline, EMBASE, and Cochrane databases. RCTs on CDS were assessed against CONSORT guidelines and the Jadad score.

32 of 3784 papers identified in the primary search were included in the final review. 181 702 patients and 7315 physicians participated in the selected trials. Most trials were performed in primary care (22), including 897 general practitioner offices. RCTs assessing CDS for asthma (4), diabetes (4), and hyperlipidemia (3) were the most common. Thirteen CDS systems (40%) were implemented in electronic medical records, and 14 (43%) provided automatic alerts. CONSORT and Jadad scores were generally low; the mean CONSORT score was 30.75 (95% CI 27.0 to 34.5), median score 32, range 21–38. Fourteen trials (43%) did not clearly define the study objective, and 11 studies (34%) did not include a sample size calculation. Outcome measures were adequately identified and defined in 23 (71%) trials; adverse events or side effects were not reported in 20 trials (62%). Thirteen trials (40%) were of superior quality according to the Jadad score (≥3 points). Six trials (18%) reported on long-term implementation of CDS.

The overall quality of reporting RCTs was low. There is a need to develop standards for reporting RCTs in medical informatics.

Medline and 11 other databases without language or date limitations to mid-2010. Randomized controlled trials (RCTs) assessing integrated MMIT were selected by two independent reviewers. Reviewers assessed study quality and extracted data. Senior staff checked accuracy.

Most of the 87 RCTs focused on clinical decision support and computerized provider order entry systems, were performed in hospitals and clinics, included primarily physicians and sometimes nurses but not other health professionals, and studied process changes related to prescribing and monitoring medication. Processes of care improved for prescribing and monitoring mostly in hospital settings, but the few studies measuring clinical outcomes showed small or no improvements. Studies were performed most frequently in the USA (n=63), Europe (n=16), and Canada (n=6).

Many studies had limited description of systems, installations, institutions, and targets of the intervention. Problems with methods and analyses were also found. Few studies addressed order communication, dispensing, or administering, non-physician prescribers or pharmacists and their MMIT tools, or patients and caregivers. Other study methods are also needed to completely understand the effects of MMIT.

Almost half of MMIT interventions improved the process of care, but few studies measured clinical outcomes. This large body of literature, although instructive, is not uniformly distributed across settings, people, medication phases, or outcomes.

We identified studies evaluating electronic ADE detection from the MEDLINE and EMBASE databases. We included studies if they contained original data and involved detection of electronic triggers using information systems. We abstracted data regarding rule characteristics including type, accuracy, and rationale.

Forty-eight studies met our inclusion criteria. Twenty-four (50%) studies reported rule accuracy but only 9 (18.8%) utilized a proper gold standard (chart review in all patients). Rule accuracy was variable and often poor (range of sensitivity: 40%–94%; specificity: 1.4%–89.8%; positive predictive value: 0.9%–64%). 5 (10.4%) studies derived or used detection rules that were defined by clinical need or the underlying ADE prevalence. Detection rules in 8 (16.7%) studies detected specific types of ADEs.

Several factors led to inaccurate ADE detection algorithms, including immature underlying information systems, non-standard event definitions, and variable methods for detection rule validation. Few ADE detection algorithms considered clinical priorities. To enhance the utility of electronic detection systems, there is a need to systematically address these factors.

Researchers conducting impact and outcome studies related to HIT.

We review and discuss count data models and illustrate their value in comparison to OLS using an example from a study of the impact of an electronic health record (EHR) on laboratory test orders. The best count data model reveals significant relationships that OLS does not detect. We conclude that comprehensive model checking is highly recommended to identify the most appropriate analytic model when the dependent variable being examined contains count data. This strategy can lead to more valid and precise findings in HIT evaluation studies.

HIT events submitted to MAUDE were retrieved using a standardized search strategy. Using an emerging classification with 32 categories of HIT problems, a subset of relevant events were iteratively analyzed to identify new categories. Two coders then independently classified the remaining events into one or more categories. Free-text descriptions were analyzed to identify the consequences of events.

Descriptive statistics by number of reported problems per category and by consequence; inter-rater reliability analysis using the statistic for the major categories and consequences.

A search of 899 768 reports from January 2008 to July 2010 yielded 1100 reports about HIT. After removing duplicate and unrelated reports, 678 reports describing 436 events remained. The authors identified four new categories to describe problems with software functionality, system configuration, interface with devices, and network configuration; the authors' classification with 32 categories of HIT problems was expanded by the addition of these four categories. Examination of the 436 events revealed 712 problems, 96% were machine-related, and 4% were problems at the human–computer interface. Almost half (46%) of the events related to hazardous circumstances. Of the 46 events (11%) associated with patient harm, four deaths were linked to HIT problems (0.9% of 436 events).

Only 0.1% of the MAUDE reports searched were related to HIT. Nevertheless, Food and Drug Administration reports did prove to be a useful new source of information about the nature of software problems and their safety implications with potential to inform strategies for safe design and implementation.

To validate the OMOP CDM, the model was instantiated into a relational database, data from 10 different observational healthcare databases were loaded into separate instances, a comprehensive array of analytic methods that operate on the data model was created, and these methods were executed against the databases to measure performance.

There was acceptable representation of the data from 10 observational databases in the OMOP CDM using the standardized terminologies selected, and a range of analytic methods was developed and executed with sufficient performance to be useful for active safety surveillance.

A prospective observational study.

We collected 4023 medication orders in a hospital for independent evaluation in two pharmacotherapy-related decision support systems. Only the more advanced system considered patient characteristics and laboratory test results in its algorithms. Two pharmacists assessed the clinical relevance of the medication alerts produced. The alert was considered relevant if the pharmacist would undertake action (eg, contact the physician or the nurse). The primary analysis concerned the positive predictive value (PPV) for clinically relevant medication alerts in both systems.

The PPV was significantly higher in the advanced system (5.8% vs 17.0%; p<0.05). Significant differences were found in the alert categories: drug–(drug) interaction (9.9% vs 14.8%; p<0.05), drug–age interaction (2.9% vs 73.3%; p<0.05), and dosing guidance (5.6% vs 16.9%; p<0.05). Including laboratory values and other patient characteristics resulted in a significantly higher PPV for the advanced CDSS compared to the basic medication alerts (12.2% vs 23.3%; p<0.05).

The advanced CDSS produced a higher proportion of clinically relevant medication alerts, but the number of irrelevant alerts remained high. To improve the PPV of the advanced CDSS, the algorithms should be optimized by identifying additional risk modifiers and more data should be made electronically available to improve the performance of the algorithms. Our study illustrates and corroborates the need for cyclic testing of technical improvements in information technology in circumstances representative of daily clinical practice.

Prospective observational study conducted within two clinical units of the Gastroenterology Department in a 1537-bed tertiary teaching hospital in Madrid (Spain).

Medication errors were measured using the disguised observation technique. Types of medication errors and their potential severity were described. The correlation between potential risk factors and medication errors was studied to identify potential causes.

In total, 2314 medication administrations to 73 patients were observed: 509 errors were recorded (22.0%)—68 (13.4%) in preparation and 441 (86.6%) in administration. The most frequent errors were use of wrong administration techniques (especially concerning food intake (13.9%)), wrong reconstitution/dilution (1.7%), omission (1.4%), and wrong infusion speed (1.2%). Errors were classified as no damage (95.7%), no damage but monitoring required (2.3%), and temporary damage (0.4%). Potential clinical severity could not be assessed in 1.6% of cases. The potential risk factors morning shift, evening shift, Anatomical Therapeutic Chemical medication class antacids, prokinetics, antibiotics and immunosuppressants, oral administration, and intravenous administration were associated with a higher risk of administration errors. No association was found with variables related to understaffing or nurse's experience.

Medication administration errors persist in units with automated prescription and dispensing. We identified a need to improve nurses' working procedures and to implement a Clinical Decision Support tool that generates recommendations about scheduling according to dietary restrictions, preparation of medication before parenteral administration, and adequate infusion rates.

We identified eight clinically significant adverse events. We used the FDA's Adverse Event Reporting System to build profiles for these adverse events based on the side effects of drugs known to produce them. We then looked for pairs of drugs that match these single-drug profiles in order to predict potential interactions. We evaluated these interactions in two independent data sets and also through a retrospective analysis of the Stanford Hospital electronic medical records.

We identified 171 novel drug interactions (for eight adverse event categories) that are significantly enriched for known drug interactions (p=0.0009) and used the electronic medical record for independently testing drug interaction hypotheses using multivariate statistical models with covariates.

Our method provides an option for detecting hidden interactions in spontaneous reporting systems by using side effect profiles to infer the presence of unreported adverse events.

A prospective controlled trial was conducted over 26 weeks. The status of the decision support tool alternated OFF (7/17/06–8/29/06), ON (8/29/06–10/10/06), OFF (10/10/06–11/28/06), and ON (11/28/06–1/16/07) in consecutive blocks during the study period. In patients ≥65 who were ordered certain benzodiazepines, opiates, non-steroidals, or sedative-hypnotics, the computer application either adjusted the dosing or suggested a different medication. Physicians could accept or reject recommendations.

The primary outcome compared medication ordering consistent with recommendations during ON versus OFF periods. Secondary outcomes included the admission rate, emergency department length of stay for discharged patients, 10-fold dosing orders, use of a second drug to reverse the original medication, and rate of ADEs using previously validated explicit chart review.

2398 orders were placed for 1407 patients over 1548 visits. The majority (49/53; 92.5%) of recommendations for alternate medications were declined. More orders were consistent with dosing recommendations during ON (403/1283; 31.4%) than OFF (256/1115; 23%) periods (p≤0.0001). 673 (43%) visits were reviewed for ADEs. The rate of ADEs was lower during ON (8/237; 3.4%) compared with OFF (31/436; 7.1%) periods (p=0.02). The remaining secondary outcomes showed no difference.

Single institution study, retrospective chart review for ADEs.

Though overall agreement with recommendations was low, real-time computerized decision support resulted in greater acceptance of medication recommendations. Fewer ADEs were observed when computerized decision support was active.

The BRIDGE-Wiz application (Building Recommendations In a Developer's Guideline Editor) uses a wizard approach to address the questions: (1) under what circumstances? (2) who? (3) ought (with what level of obligation?) (4) to do what? (5) to whom? (6) how and why? Controlled natural language was applied to create and populate a template for recommendation statements.

The application was used by five national panels to develop guidelines. In general, panelists agreed that the software helped to formalize a process for authoring guideline recommendations and deemed the application usable and useful.

Use of BRIDGE-Wiz promotes clarity of recommendations by limiting verb choices, building active voice recommendations, incorporating decidability and executability checks, and limiting Boolean connectors. It enhances transparency by incorporating systematic appraisal of evidence quality, benefits, and harms. BRIDGE-Wiz promotes implementability by providing a pseudocode rule, suggesting deontic modals, and limiting the use of ‘consider’.

Users found that BRIDGE-Wiz facilitates the development of clear, transparent, and implementable guideline recommendations.

A population-based proband-oriented pedigree information system with ties of consanguinity based on both population-based household registry data and Keelung Community Integrated Screening data was proposed to build a comprehensive extended family pedigree structure to accommodate a series of genetic studies on different diseases. We also developed an algorithm to efficiently assess how well theoretical family relationships affecting the occurrence of diseases across three generations with respect to the relative relationship score, a quantitative indicator of genetic influence, were captured.

We applied this population-based proband-oriented pedigree information system to estimate the rate of hypertension with various relative relationships given the selection of probands. The degree of capturing complete familial relationships was assessed for three generations. The risk for early onset of hypertension was proportional to the proband-oriented relative relationship score with 2% increased risk and 1% correction for incomplete capture.

The population-based proband-oriented pedigree information system is powerful and can support various genetic descriptive and analytic epidemiological studies.

Retrospective case–control chart review of 240 patients during the years 2008 and 2009. Patient demographic and clinical information was extracted from our online medical records, and portal use metrics were provided by Information Systems. Descriptive statistics were utilized to explore characteristics of portal users, how the portal is used, and what associations exist between medical resource utilization and active portal use. Logistic regression identified independent patient predictors and barriers to portal use.

Portal users tended to be young professionals with minimal physical disability. The most frequently used portal feature was secure patient–physician messaging. Message content largely consisted of requests for medications or refills in addition to self-reported side effects. Independent predictors and barriers of portal use include the number of medications prescribed by our staff (OR 1.69, p<0.0001), Caucasian ethnicity (OR 5.04, p=0.007), arm and hand disability (OR 0.23, p=0.01), and impaired vision (OR 0.31, p=0.01).

MS patients use the internet in a greater proportion than the general US population, yet physical disability limits their access. Technological adaptations such as voice-activated commands and easy font-size adjustment may help patients overcome these barriers.

Future research should explore the influence of portal technology on healthcare resource utilization and cost. Additional emedicine applications could be linked to the patient portal for disease monitoring and prospective investigation.

Researchers developed four CHI intervention use cases representing two distinct patient populations (patients with diabetes with high blood pressure, post-bariatric surgery patients), two commercial off-the-shelf CHI applications (Microsoft HealthVault, Google Health), and related devices (blood pressure monitor, pedometer, weight scale). Three patient proxies tested each intervention for 10 days.

The patient proxies recorded their challenges while completing use case tasks, rating the severity of each challenge based on how much it hindered their use of the intervention. Two independent evaluators categorized the challenges by human factors domain (physical, cognitive, macroergonomic).

The use case-based approach resulted in the identification of 122 challenges, with 12% physical, 50% cognitive and 38% macroergonomic. Thirty-nine challenges (32%) were at least moderately severe. Nine of 22 use case tasks (41%) accounted for 72% of the challenges.

The study used two patient proxies and addressed two specific patient populations and low-cost, off-the-shelf CHI interventions, which may not perfectly generalize to a larger number of proxies, actual patient populations, or other CHI interventions.

CHI designers can employ the use case-based evaluation approach to assess the fit of a CHI intervention with patients' health work, in the context of their daily activities and environment, which would be difficult or impossible to evaluate by laboratory-based studies.

We conducted a telephone survey of patients in one urban general internal medicine clinic. Patients were eligible if they did not enroll within 30 days of receiving an electronic order inviting participation. Our primary outcomes were: (a) reasons for not enrolling in the patient portal; (b) reasons for not attempting enrollment; and (c) perceived benefits of the portal.

Participants' (N=159) mean age was 51 years, 48% were black, 72% female, and 70% had a college degree or greater. 63% of respondents not enrolling reported never attempting enrollment despite remembering receiving an order. Most of these 63% did not attempt enrollment because of lack of information or motivation. Smaller proportions reported not attempting enrollment because of negative attitudes toward the portal (30%) or computer related obstacles (8%). Overall, respondents favorably viewed most patient portal features, however black respondents were less likely than white respondents to consider features assisting self-management such as getting test results (69% vs 86%; p<0.05) as important. Adjusting for age, gender, education, and chronic disease did not substantially change results.

Strategies to increase enrollment in patient portals need to ensure patients understand patient portal features and receive follow-up reminders. Interventions to reduce racial disparities in enrollment must address attitudinal barriers and not focus solely on improving access.

To gain insight into community-based physicians' goals, environments, tasks, and desired support tools, we used a human–computer interaction model that was based in grounded theory. We conducted 30 recorded interviews with, and 25 observations of, primary care providers within 15 urban and rural community-based clinics across Oregon. Participants were members of three healthcare organizations with different commercial electronic health record systems. We used a grounded theory approach to analyze data and develop a user-centered definition of CDS and themes related to desired CDS functionalities.

Physicians viewed CDS as a set of software tools that provide alerts, prompts, and reference tools, but not tools to support patient management, clinical operations, or workflow, which they would like. They want CDS to enhance physician–patient relationships, redirect work among staff, and provide time-saving tools. Participants were generally dissatisfied with current CDS capabilities and overall electronic health record usability.

Physicians identified different aspects of decision-making in need of support: clinical decision-making such as medication administration and treatment, and cognitive decision-making that enhances relationships and interactions with patients and staff.

Physicians expressed a need for decision support that extended beyond their own current definitions. To meet this requirement, decision support tools must integrate functions that align time and resources in ways that assist providers in a broad range of decisions.

A 43-question anonymous survey distributed electronically to relevant online communities.

Data on user demographic characteristics, modes and purposes of use, means and frequencies of access, satisfaction with SNOMED CT content coverage and quality and with the change request mechanism were recorded.

The survey was conducted in January 2010 and elicited 215 responses. Details regarding users' profiles, modes of use and access were reported elsewhere. The coverage of SNOMED CT was perceived to be at least 85% complete by 42% of responders, and 60% were at least satisfied with its quality. Various deficiencies were encountered at least ‘somewhat often’ by 28–61% of responders. Incorrect data were more bothersome than missing data. Users indicated that significant resources should be allocated to more consistent and complete conceptual representations and to further enhance content coverage. Enhanced synonym coverage and the introduction of textual definitions were important to users (54% and 63%, respectively).

A survey format with limited control over recruitment and selection bias. Lack of information regarding the SNOMED CT version used by responders.

Despite overall satisfaction, direct users indicated a strong desire to improve consistency, quality, and completeness of conceptual representations and concept details, as well as a continued desire to expand coverage. The survey provides much needed data for informed decisions regarding the use and development goals of SNOMED CT. Focused periodical surveys are warranted.

An 18-month, retrospective study of acute care admissions at a single Veterans Affairs medical center using computerized provider order entry (CPOE).

Patients included had at least one warfarin cDDI alert. Chart reviews included baseline laboratory values and demographics, provider actions, patient outcomes, and associated factors, including other interacting medications and number of simultaneously processed alerts.

137 admissions were included (133 unique patients). Amiodarone, vitamin E in a multivitamin, sulfamethoxazole, and levothyroxine accounted for 75% of warfarin cDDI. Provider responses were clinically appropriate in 19.7% of admissions and pharmacist responses were appropriate in 9.5% of admissions. There were 50 ADE (36.6% of admissions) with warfarin; 80% were rated as having no or mild clinical effect. An increased number of non-critical alerts at the time of the reference cDDI alert was the only variable associated with an inappropriate provider response (p=0.01).

This study was limited by being a retrospective review and the possibility of confounding variables, such as other interacting medications.

The large number of CPOE alerts may lead to inappropriate responses by providers and pharmacists. The high rate of ADE suggests a need for improved medication management systems for patients on warfarin. This study highlights the possibility of alert fatigue contributing to the high prevalence of inappropriate alert over-ride text responses.

The survey is grounded in the unified theory of acceptance and use of technology and an adapted accident causation model. Development of the instrument was also informed by a review of the extant literature on prescribers' attitude toward computerized medication safety alerts and common prescriber-provided reasons for overriding. To refine and validate the survey, we conducted a two-stage empirical validation study consisting of a pretest with a panel of domain experts followed by a field test among all eligible prescribers at our institution.

The resulting survey instrument contains 28 questionnaire items assessing six theoretical dimensions: performance expectancy, effort expectancy, social influence, facilitating conditions, perceived fatigue, and perceived use behavior. Satisfactory results were obtained from the field validation; however, a few potential issues were also identified. We analyzed these issues accordingly and the results led to the final survey instrument as well as usage recommendations.

High override rates of computerized medication safety alerts have been a prevalent problem. They are usually caused by, or manifested in, issues of poor end user acceptance. However, standardized research tools for assessing and understanding end users' perception are currently lacking, which inhibits knowledge accumulation and consequently forgoes improvement opportunities. The survey instrument presented in this paper may help fill this methodological gap.

We developed and empirically validated a survey instrument that may be useful for future research on DDI alerts and other types of computerized medication safety alerts more generally.

The authors previously reviewed human-factors principles for relevance to medication-related decision support alerts. In this study, instrument items were developed for assessing the appropriate implementation of these human-factors principles in drug–drug interaction (DDI) alerts. User feedback regarding nine electronic medical records was considered during the development process. Content validity, construct validity through correlation analysis, and inter-rater reliability were assessed.

The final version of the instrument included 26 items associated with nine human-factors principles. Content validation on three systems resulted in the addition of one principle (Corrective Actions) to the instrument and the elimination of eight items. Additionally, the wording of eight items was altered. Correlation analysis suggests a direct relationship between system age and performance of DDI alerts (p=0.0016). Inter-rater reliability indicated substantial agreement between raters (=0.764).

The authors developed and gathered preliminary evidence for the validity of an instrument that measures the appropriate use of human-factors principles in the design and display of DDI alerts. Designers of DDI alerts may use the instrument to improve usability and increase user acceptance of medication alerts, and organizations selecting an electronic medical record may find the instrument helpful in meeting their clinicians' usability needs.

To develop a new methodology that combines existing data mining algorithms with chemical information by analysis of molecular fingerprints to enhance initial ADE signals generated from AERS, and to provide a decision support mechanism to facilitate the identification of novel adverse events.

The method achieved a significant improvement in precision in identifying known ADE, and a more than twofold signal enhancement when applied to the ADE rhabdomyolysis. The simplicity of the method assists in highlighting the etiology of the ADE by identifying structurally similar drugs. A set of drugs with strong evidence from both AERS and molecular fingerprint-based modeling is constructed for further analysis.

The results demonstrate that the proposed methodology could be used as a pharmacovigilance decision support tool to facilitate ADE detection.

A descriptive study using the University of Pennsylvania Health System outpatient EMR to simulate a prospective algorithm to identify exposures during pregnancy to category X medications, soon enough to intervene and potentially prevent the exposure. A subsequent post-hoc algorithm was also tested, working backwards from pregnancy endpoints, to search for possible exposures that should have been detected.

Category X medications prescribed to pregnant patients.

The alert simulation identified 2201 pregnancies with 16 969 pregnancy months (excluding abortions and ectopic pregnancies). Of these, 30 appeared to have an order for a non-hormone category X medication during pregnancy. However, none of the 30 ‘exposed pregnancies’ were confirmed as true exposures in medical records review. The post-hoc algorithm identified 5841 pregnancies with 64 exposed pregnancies in 52 569 risk months, only one of which was a confirmed case.

Category X medications may indeed be used in pregnancy, although rarely. However, most patients identified by the algorithm as exposed in pregnancy were not truly exposed. Therefore, implementing an electronic warning without evaluation would have inconvenienced prescribers, possibly hurting some patients (leading to non-use of needed drugs), with no benefit. These data demonstrate that computerized physician order entry interventions should be selected and evaluated carefully even before their use, using alert simulations such as that performed here, rather than just taken off the shelf and accepted as credible without formal evaluation.

To compare the characteristics of clinicians who did and did not use novel EHR functionality, we conducted a retrospective analysis of the intervention arm of a randomized trial of new EHR-based tobacco treatment functionality.

The novel functionality was used by 103 of 207 (50%) clinicians. Staff physicians were more likely than trainees to use the functionality (64% vs 37%; p<0.001). Clinicians who graduated more than 10 years previously were more likely to use the functionality than those who graduated less than 10 years previously (64% vs 42%; p<0.01). Clinicians with higher patient volumes were more likely to use the functionality (lowest quartile of number of patient visits, 25%; 2nd quartile, 38%; 3rd quartile, 65%; highest quartile, 71%; p<0.001). Clinicians who saw patients with more documented problems were more likely to use the functionality (lowest tertile of documented patient problems, 38%; 2nd tertile, 58%; highest tertile, 54%; p=0.04). In multivariable modeling, independent predictors of use were the number of patient visits (OR 1.2 per 100 additional patients; 95% CI 1.1 to 1.4) and number of documented problems (OR 2.9 per average additional problem; 95% CI 1.4 to 6.1).

Contrary to conventional wisdom, clinically busier physicians seeing patients with more documented problems were more likely to use novel EHR functionality.

Borrowing concepts from Entity–Attribute–Value and from enterprise data warehousing, the authors designed an alternative called the Dimensional Bus model and used it to integrate electronic medical record, sponsored study, and biorepository data. Each type of observational collection has its own table, and the structure of these tables varies to suit the source data. The observational tables are linked to the Bus, which holds provenance information and links to various classificatory dimensions that amplify the meaning of the data or facilitate its query and exposure management.

The authors implemented a Bus-based clinical research data repository with a query system that flexibly manages data access and confidentiality, facilitates catalog search, and readily formulates and compiles complex queries.

The design provides a workable way to manage and query mixed schemas in a data warehouse.

The authors' experience with informatics for integrating biology and the bedside (i2b2) use cases indicates that the privacy of the patient should be considered on three fronts: technical de-identification of the data, trust in the researcher and the research, and the security of the underlying technical platforms.

The security structure of i2b2 is implemented based on consideration of all three fronts. It has been supported with several use cases across the USA, resulting in five privacy categories of users that serve to protect the data while supporting the use cases.

The i2b2 architecture is designed to provide consistency and faithfully implement these user privacy categories. These privacy categories help reflect the policy of both the Health Insurance Portability and Accountability Act and the provisions of the National Research Act of 1974, as embodied by current institutional review boards.

By implementing a holistic approach to patient privacy solutions, i2b2 is able to help close the gap between principle and practice.

Lagged linear correlation was calculated between seven clinical laboratory values and 30 clinical concepts extracted from resident signout notes from a 22-year, 3-million-patient database of electronic health records. Time points were interpolated, and patients were normalized to reduce inter-patient effects.

The method revealed several types of associations with detailed temporal patterns. Definitional associations included low blood potassium preceding ‘hypokalemia.’ Low potassium preceding the drug spironolactone with high potassium following spironolactone exemplified intentional and physiologic associations, respectively. Counterintuitive results such as the fact that diseases appeared to follow their effects may be due to the workflow of healthcare, in which clinical findings precede the clinician's diagnosis of a disease even though the disease actually preceded the findings. Fully exploiting time by interpolating time points produced less noisy results.

Electronic health records are not direct reflections of the patient state, but rather reflections of the healthcare process and the recording process. With proper techniques and understanding, and with proper incorporation of time, interpretable associations can be derived from a large clinical database.

A large, heterogeneous clinical database can reveal clinical associations, time is an important feature, and care must be taken to interpret the results.

An analysis pipeline called eligibility criteria extraction and representation (EliXR) was developed that integrates syntactic parsing and tree pattern mining to discover common semantic patterns in 1000 eligibility criteria randomly selected from http://ClinicalTrials.gov. The semantic patterns were aggregated and enriched with unified medical language systems semantic knowledge to form a semantic representation for clinical research eligibility criteria.

The authors arrived at 175 semantic patterns, which form 12 semantic role labels connected by their frequent semantic relations in a semantic network.

Three raters independently annotated all the sentence segments (N=396) for 79 test eligibility criteria using the 12 top-level semantic role labels. Eight-six per cent (339) of the sentence segments were unanimously labelled correctly and 13.8% (55) were correctly labelled by two raters. The Fleiss' was 0.88, indicating a nearly perfect interrater agreement.

This study present a semi-automated data-driven approach to developing a semantic network that aligns well with the top-level information structure in clinical research eligibility criteria text and demonstrates the feasibility of using the resulting semantic role labels to generate semistructured eligibility criteria with nearly perfect interrater reliability.

The authors have conducted a multipart model formulation and validation process, focusing on the development of a methodological and technical approach to using CKDD to support hypothesis discovery for in silico science. The model the authors have developed is known as the Translational Ontology-anchored Knowledge Discovery Engine (TOKEn). This model utilizes a specific CKDD approach known as Constructive Induction to identify and prioritize potential hypotheses related to the meaningful semantic relationships between variables found in large-scale and heterogeneous biomedical data sets.

The authors have verified and validated TOKEn in the context of a translational research data repository maintained by the NCI-funded Chronic Lymphocytic Leukemia Research Consortium. Such studies have shown that TOKEn is: (1) computationally tractable; and (2) able to generate valid and potentially useful hypotheses concerning relationships between phenotypic and biomolecular variables in that data collection.

The TOKEn model represents a potentially useful and systematic approach to knowledge synthesis for in silico discovery science in the context of large-scale and multidimensional research data sets.

We have developed a multi-layered knowledge representation framework for structuring guideline recommendations for implementation in a variety of CDS contexts. In this framework, guideline recommendations are increasingly structured through four layers, successively transforming a narrative text recommendation into input for a CDS system. We have used this framework to implement rules for a CDS service based on three guidelines. We also conducted a preliminary evaluation, where we asked CDS experts at four institutions to rate the implementability of six recommendations from the three guidelines.

The experience in using the framework and the preliminary evaluation indicate that this approach has promise in creating structured knowledge, to implement in CDS systems, that is usable across organizations.

Pattern matching rules were manually developed through examining keywords and expression patterns of side effects to discover an individual side effect and causative drug relationship. A combination of machine learning (C4.5) using side effect keyword features and pattern matching rules was used to extract sentences that contain side effect and causative drug pairs, enabling the system to discover most side effect occurrences. Our system was implemented as a module within the clinical Text Analysis and Knowledge Extraction System.

The system was tested in the domain of psychiatry and psychology. The rule-based system extracting side effects and causative drugs produced an F score of 0.80 (0.55 excluding allergy section). The hybrid system identifying side effect sentences had an F score of 0.75 (0.56 excluding allergy section) but covered more side effect and causative drug pairs than individual side effect extraction.

The rule-based system was able to identify most side effects expressed by clear indication words. More sophisticated semantic processing is required to handle complex side effect descriptions in the narrative. We demonstrated that our system can be trained to identify sentences with complex side effect descriptions that can be submitted to a human expert for further abstraction.

Our system was able to extract most physician-asserted drug side effects. It can be used in either an automated mode for side effect extraction or semi-automated mode to identify side effect sentences that can significantly simplify abstraction by a human expert.

Using a set of quality measures published by physician specialty societies, we implemented an NLP engine that extracts 21 variables for 19 quality measures from free-text colonoscopy and pathology reports. We evaluated the performance of the NLP engine on a test set of 453 colonoscopy reports and 226 pathology reports, considering accuracy in extracting the values of the target variables from text, and the reliability of the outcomes of the quality measures as computed from the NLP-extracted information.

The average accuracy of the NLP engine over all variables was 0.89 (range: 0.62–1.0) and the average F measure over all variables was 0.74 (range: 0.49–0.89). The average agreement score, measured as Cohen's , between the manually established and NLP-derived outcomes of the quality measures was 0.62 (range: 0.09–0.86).

For nine of the 19 colonoscopy quality measures, the agreement score was 0.70 or above, which we consider a sufficient score for the NLP-derived outcomes of these measures to be practically useful for quality measurement.

The use of NLP for information extraction from free-text colonoscopy and pathology reports creates opportunities for large scale, routine quality measurement, which can support quality improvement in colonoscopy care.

The objective of this study was to systematically review the recent literature around the impact of the EMR/EHR within primary-care outpatient practices.

Searches of Medline, EMBASE, CINAHL, ABI Inform, and Cochrane Library were conducted to identify articles published between January 1998 and January 2010. The gray literature and reference lists of included articles were also searched. 30 studies met inclusion criteria.

The EMR/EHR appears to have structural and process benefits, but the impact on clinical outcomes is less clear. Using Donabedian's framework, five articles focused on the impact on healthcare structure, 21 explored healthcare process issues, and four focused on health-related outcomes.

A qualitative meta-synthesis was performed on studies published in English between 1995 and 2010 that addressed the modeling process and reported the exposition of a new methodology, model, system implementation, or system architecture. Thematic analysis, principal component analysis (PCA) and data visualisation techniques were used to identify and cluster the underlying implementation ‘challenge’ themes.

One hundred and eight relevant studies were selected for review. Twenty-five underlying ‘challenge’ themes were identified. These were clustered into 10 distinct groups, from which a conceptual model of the implementation process was developed.

We found that the development of systems supporting individual clinical decisions is evolving toward the implementation of adaptable care pathways on the semantic web, incorporating formal, clinical, and organizational ontologies, and the use of workflow management systems. These architectures now need to be implemented and evaluated on a wider scale within clinical settings.

14 specialty teams (46 doctors) were shadowed by the investigator while on their ward-rounds and 16 prescribers from these teams were interviewed.

Senior doctors were highly influential in prescribing decisions during ward-rounds but rarely used the computerized provider order entry system. Junior doctors entered the majority of medication orders into the system, nearly always ignored computerized alerts and never raised their occurrence with other doctors on ward-rounds. Interviews with doctors revealed that some decision support features were valued but most were not perceived to be useful.

The computerized alerts failed to target the doctors who were making the prescribing decisions on ward-rounds. Senior doctors were the decision makers, yet the junior doctors who used the system received the alerts. As a result, the alert information was generally ignored and not incorporated into the decision-making processes on ward-rounds. The greatest value of decision support in this setting may be in non-ward-round situations where senior doctors are less influential. Identifying how prescribing systems are used during different clinical activities can guide the design of decision support that effectively supports users in different situations. If confirmed, the findings reported here present a specific focus and user group for designers of medication decision support.

An international Delphi study with two quantitative rounds. 69 researchers with expertise in computerized physician order entry (CPOE) systems were asked to estimate the usefulness of 20 possible context factors, and to assess the potential impact of six innovative ways of delivering alert information on adverse drug event (ADE) rates.

Participants identified the following top five context information items (in descending order of usefulness): (1) severity of the effect of the ADE the alert refers to; (2) clinical status of the patient; (3) probability of occurrence of the ADE the alert refers to; (4) risk factors of the patient; and (5) strength of evidence on which the alert is built. The ways of delivering alert information with the highest estimated ADE reduction potential are active alerting, proactive prescription simulation and a patient medication module that gives patient-oriented alert information.

Most participants had a research-oriented focus; therefore the results may not reflect the opinions of CPOE users or CPOE implementers.

The study results may provide CPOE system developers and healthcare institutions with information on how to design more effective alert mechanisms.

This is a retrospective cohort study of 3850 computer-generated prescriptions received by a commercial outpatient pharmacy chain across three states over 4 weeks in 2008. A clinician panel reviewed the prescriptions using a previously described method to identify and classify medication errors. Primary outcomes were the incidence of medication errors; potential adverse drug events, defined as errors with potential for harm; and rate of prescribing errors by error type and by prescribing system.

Of 3850 prescriptions, 452 (11.7%) contained 466 total errors, of which 163 (35.0%) were considered potential adverse drug events. Error rates varied by computerized prescribing system, from 5.1% to 37.5%. The most common error was omitted information (60.7% of all errors).

About one in 10 computer-generated prescriptions included at least one error, of which a third had potential for harm. This is consistent with the literature on manual handwritten prescription error rates. The number, type, and severity of errors varied by computerized prescribing system, suggesting that some systems may be better at preventing errors than others.

Implementing a computerized prescribing system without comprehensive functionality and processes in place to ensure meaningful system use does not decrease medication errors. The authors offer targeted recommendations on improving computerized prescribing systems to prevent errors.

CPOE with duplicate medication order alerts was implemented in a 400-bed Northeastern US community tertiary care teaching hospital. In a pre-implementation post-implementation design, trained nurses used chart review, computer-generated reports of medication orders, provider alerts, and staff reports to identify medication errors in two intensive care units (ICUs).

Medication error data were adjudicated by a physician and a human factors engineer for error stage and type. A qualitative analysis of duplicate medication ordering errors was performed to identify contributing factors.

Data were collected for 4147 patient-days pre-implementation and 4013 patient-days post-implementation. Duplicate medication ordering errors increased after CPOE implementation (pre: 48 errors, 2.6% total; post: 167 errors, 8.1% total; p<0.0001). Most post-implementation duplicate orders were either for the identical order or the same medication. Contributing factors included: (1) provider ordering practices and computer availability, for example, two orders placed within minutes by different providers on rounds; (2) communication and hand-offs, for example, duplicate orders around shift change; (3) CDS and medication database design, for example confusing alert content, high false-positive alert rate, and CDS algorithms missing true duplicates; (4) CPOE data display, for example, difficulty reviewing existing orders; and (5) local CDS design, for example, medications in order sets defaulted as ordered.

Duplicate medication order errors increased with CPOE and CDS implementation. Many work system factors, including the CPOE, CDS, and medication database design, contributed to their occurrence.

A pop-up alert was created for providers when an individual's platelet values had decreased by 50% or to <100 000/mm³ in the setting of recent heparin exposure. The authors retrospectively compared inpatients admitted between January 24, 2008 and August 24, 2008 to a control group admitted 1 year prior to the HIT alert. The primary outcome was a change in HIT antibody testing. Secondary outcomes included an assessment of incidence of HIT antibody positivity, percentage of patients started on a direct thrombin inhibitor (DTI), length of stay and overall mortality.

There were 1006 and 1081 patients in the control and intervention groups, respectively. There was a 33% relative increase in HIT antibody test orders (p=0.01), and 33% more of these tests were ordered the first day after the criteria were met when a pop-up alert was given (p=0.03). Heparin was discontinued in 25% more patients in the alerted group (p=0.01), and more direct thrombin inhibitors were ordered for them (p=0.03). The number who tested HIT antibody-positive did not differ, however, between the two groups (p=0.99). The length of stay and mortality were similar in both groups.

The HIT alert significantly impacted provider behaviors. However, the alert did not result in more cases of HIT being detected or an improvement in overall mortality. Our findings do not support implementation of a computerized HIT alert.

A randomized study of 24 junior doctors each performing 30 simulated prescribing tasks in random order with a prototype e-prescribing system. Using a within-participant design, doctors were randomized to be shown one of three types of e-prescribing alert (modal, non-modal, no alert) during each prescribing task.

The main outcome measure was prescribing error rate. Structured interviews were performed to elicit participants' preferences for the prescribing alerts and their views on clinical decision support systems.

Participants exposed to modal alerts were 11.6 times less likely to make a prescribing error than those not shown an alert (OR 11.56, 95% CI 6.00 to 22.26). Those shown a non-modal alert were 3.2 times less likely to make a prescribing error (OR 3.18, 95% CI 1.91 to 5.30) than those not shown an alert. The error rate with non-modal alerts was 3.6 times higher than with modal alerts (95% CI 1.88 to 7.04).

Both kinds of e-prescribing alerts significantly reduced prescribing error rates, but modal alerts were over three times more effective than non-modal alerts. This study provides new evidence about the relative effects of modal and non-modal alerts on prescribing outcomes.

Adequate IT is required to sufficiently support a multicenter reporting system. The CMR system consists of a website, a database, a web-based reporting form, an application to import reports generated in other reporting systems, an application to generate an overview of reported medication incidents, and a national warning system for healthcare providers.

From the start of CMR 90 of all 93 (96.8%) hospitals and 872 of 1948 (44.8%) community pharmacies participated. Between March 2006 and March 2010 the CMR comprised 15 694 reports of incidents. In the period from March 2010 to March 2011, 1642 reports were submitted by community pharmacies in CMR and the hospitals submitted 2517 reports. CMR is similar to various systems in other countries, but it seems to use more IT applications.

The CMR is developing into a nationwide reporting system of medication incidents in The Netherlands, in which hospitals, community pharmacies, mental healthcare organizations and general practitioners participate.

The architecture of the system met the requirements of a nationwide reporting system across different healthcare providers.

Time-series analysis at a large internal medicine practice using a commercial EHR. All patients eligible for each measure were included (range approximately 100–7500).

The proportion of eligible patients in the practice who satisfied each of 15 quality measures after removing those with exceptions from the denominator. To analyze changes in performance for individual physicians, two composite measures were used: prescribing seven essential medications and completion of five preventive services.

During the year after implementing pre-encounter reminders, performance continued to improve for eight measures, remained stable for four, and declined for three. Physicians with the worst performance at the start of the pre-encounter reminders showed little absolute improvement over the next year, and most remained below the median performance for physicians in the practice.

Paper pre-encounter reminders did not appear to improve performance beyond electronic point-of-care reminders in the EHR alone. Lagging performance is likely not due to providers' EHR workflow alone, and trying to step backwards and use paper reminders in addition to point-of-care reminders in the EHR may not be an effective strategy for engaging slow adopters.

The authors analyzed data from two cross-sectional survey questionnaires distributed to nurses working in four ICUs at a northeastern US regional medical center, 3 months and 12 months after EHR implementation.

Survey items were drawn from established instruments used to measure EHR acceptance and usability, and the usefulness of three EHR functionalities, specifically computerized provider order entry (CPOE), the electronic medication administration record (eMAR), and a nursing documentation flowsheet.

On average, ICU nurses were more accepting of the EHR at 12 months as compared to 3 months. They also perceived the EHR as being more usable and both CPOE and eMAR as being more useful. Multivariate hierarchical modeling indicated that EHR usability and CPOE usefulness predicted EHR acceptance at both 3 and 12 months. At 3 months postimplementation, eMAR usefulness predicted EHR acceptance, but its effect disappeared at 12 months. Nursing flowsheet usefulness predicted EHR acceptance but only at 12 months.

As the push toward implementation of EHR technology continues, more hospitals will face issues related to acceptance of EHR technology by staff caring for critically ill patients. This research suggests that factors related to technology design have strong effects on acceptance, even 1 year following the EHR implementation.

The approach, referred to as partnership model, was developed and iteratively refined through the research team's previous work on implementing health information technology (HIT) in over 30 safety net practices. This paper uses two case studies to illustrate how the model was applied to help two nurse-managed health centers (NMHC), a particularly vulnerable primary care setting, implement EHR and get prepared to meet the meaningful use criteria.

The strong focus of the model on continuous quality improvement led to eventual implementation success at both sites, despite difficulties encountered during the initial stages of the project.

There has been a lack of research, particularly in resource-limited primary care settings, on strategies for abating provider anxiety and preparing them to manage complex changes associated with EHR uptake. The partnership model described in this paper may provide useful insights into the work shepherded by HIT regional extension centers dedicated to supporting resource-limited communities disproportionally affected by EHR adoption barriers.

NMHC, similar to other primary care settings, are often poorly resourced, understaffed, and lack the necessary expertise to deploy EHR and integrate its use into their day-to-day practice. This study demonstrates that implementation of EHR, a prerequisite to meaningful use, can be successfully achieved in this setting, and partnership efforts extending far beyond the initial software deployment stage may be the key.

A mixed-method three-group comparative design was used. The PRECEDE/PROCEED implementation model was used to qualitatively identify key factors in the implementation process. These results were further explored in a quantitative analysis.

Thirty-three primary care clinics at three institutions (Intermountain Healthcare, VA Salt Lake City Health Care System, and University of Utah) participated. The program consisted of an onsite, didactic session, QI planning and 6 months of intense implementation support.

Completion rate was 82% with an average improvement rate of 21%. Important predisposing factors for success included an established electronic record and a culture of quality. The reinforcing and enabling factors included free continuing medical education credits, feedback, IT access, and flexible support. The relationship between IT and QI emerged as a central factor. Quantitative analysis found significant differences between institutions for pre–post changes even after the number and category of implementation strategies had been controlled for.

The analysis illustrates the complex dependence between IT interventions, institutional characteristics, and implementation practices. Access to IT tools and data by individual clinicians may be a key factor for the success of QI projects. Institutions vary widely in the degree of access to IT tools and support. This article suggests that more attention be paid to the QI and IT department relationship.

eCancerCare^Bladder and the EMR were used to retrieve data and produce clinical reports. Twelve participants (four attending staff, four fellows, and four residents) used either eCancerCare^Bladder or the EMR in two clinical scenarios simulating cystoscopy surveillance visits for bladder cancer follow-up.

Time to retrieve and quality of review of the patient history; time to produce and completeness of a cystoscopy report. Finally, participants provided a global assessment of their computer literacy, familiarity with the two systems, and system preference.

eCancerCare^Bladder was faster for data retrieval (scenario 1: 146 s vs 245 s, p=0.019; scenario 2: 306 vs 415 s, NS), but non-significantly slower to generate a clinical report. The quality of the report was better in the eCancerCare^Bladder system (scenario 1: p<0.001; scenario 2: p=0.11). User satisfaction was higher with the eCancerCare^Bladder system, and 11/12 participants preferred to use this system.

The small sample size affected the power of our study to detect differences.

Use of a specific data management tool does not appear to significantly reduce user time, but the results suggest improvement in the level of care and documentation and preference by users. Also, the use of simulated scenarios in a laboratory setting appears to be a valid method for comparing the usability of clinical software.

WIISARD combined advanced networking technology with electronic triage tags that reported victims' position and recorded medical information, with wireless pulse-oximeters that monitored patient vital signs, and a wireless electronic medical record (EMR) for disaster care. The EMR system included WiFi handheld devices with barcode scanners (used by front-line responders) and computer tablets with role-tailored software (used by managers of the triage, treatment, transport and medical communications teams). An additional software system provided situational awareness for the incident commander. The WIISARD system was evaluated in a large-scale simulation exercise designed for training first responders. A randomized trial was overlaid on this exercise with 100 simulated victims, 50 in a control pathway (paper-based), and 50 in completely electronic WIISARD pathway. All patients in the electronic pathway were cared for within the WIISARD system without paper-based workarounds.

WIISARD reduced the rate of the missing and/or duplicated patient identifiers (0% vs 47%, p<0.001). The total time of the field was nearly identical (38:20 vs 38:23, IQR 26:53–1:05:32 vs 18:55–57:22).

Overall, the results of WIISARD show that wireless EMR systems for care of the victims of disasters would be complex to develop but potentially feasible to build and deploy, and likely to improve the quality of information available for the delivery of care during disasters.

We analyzed patient visits in one community in which a high proportion of providers were using an electronic health record and participating in data exchange. Using claims data from one large private payer for individuals under age 65 years, we computed the number of visits to a provider which involved transitions in care from other providers as a percentage of total visits. We calculated this ‘transition percentage’ for individual providers and medical groups.

On average, excluding radiology and pathology, approximately 51% of visits involved care transitions between individual providers in the community and 36%–41% involved transitions between medical groups. There was substantial variation in transition percentage across medical specialties, within specialties and across medical groups. Specialists tended to have higher transition percentages and smaller ranges within specialty than primary care physicians, who ranged from 32% to 95% (including transitions involving radiology and pathology). The transition percentages of pediatric practices were similar to those of adult primary care, except that many transitions occurred among pediatric physicians within a single medical group.

Care transition patterns differed substantially by type of practice and should be considered in designing incentives to foster providers' meaningful use of health data exchange services.

To develop and validate methods of automatically inferring patient problems from clinical and billing data, and to provide a knowledge base for inferring problems.

We identified 17 target conditions and designed and validated a set of rules for identifying patient problems based on medications, laboratory results, billing codes, and vital signs. A panel of physicians provided input on a preliminary set of rules. Based on this input, we tested candidate rules on a sample of 100 000 patient records to assess their performance compared to gold standard manual chart review. The physician panel selected a final rule for each condition, which was validated on an independent sample of 100 000 records to assess its accuracy.

Seventeen rules were developed for inferring patient problems. Analysis using a validation set of 100 000 randomly selected patients showed high sensitivity (range: 62.8–100.0%) and positive predictive value (range: 79.8–99.6%) for most rules. Overall, the inference rules performed better than using either the problem list or billing data alone.

We developed and validated a set of rules for inferring patient problems. These rules have a variety of applications, including clinical decision support, care improvement, augmentation of the problem list, and identification of patients for research cohorts.

We evaluated recommendations from Malawi's ART guidelines using GuideLine Implementability Appraisal criteria. Recommendations that passed selected criteria were converted into ratio-based performance measures. We queried representative EMR data to determine the feasibility of generating feedback for each performance measure, summed clinical encounters representing each performance measure's denominator, and then measured the distribution of encounter frequency for individual HCWs across nurse and clinical officer groups.

We analyzed 423 831 encounters in the EMR data and generated automated feedback for 21 recommendations (12%) from Malawi's ART guidelines. We identified 11 nurse recommendations and eight clinical officer recommendations. Individual nurses and clinical officers had an average of 45 and 59 encounters per month, per recommendation, respectively. Another 37 recommendations (21%) would support audit and feedback if additional routine EMR data are captured and temporal constraints are modeled.

It appears feasible to implement automated guideline adherence feedback that could potentially improve HCW performance and supervision. Feedback reports may support workplace learning by increasing HCWs' opportunities to reflect on their performance.

A moderate number of recommendations from Malawi's ART guidelines can be used to generate automated guideline adherence feedback using existing EMR data. Further study is needed to determine the receptivity of HCWs to peer comparison feedback and barriers to implementation of automated audit and feedback in low-resource settings.

This tutorial targets the medical informatics generalist who has limited acquaintance with the principles behind NLP and/or limited knowledge of the current state of the art.

We describe the historical evolution of NLP, and summarize common NLP sub-problems in this extensive field. We then provide a synopsis of selected highlights of medical NLP efforts. After providing a brief description of common machine-learning approaches that are being used for diverse NLP sub-problems, we discuss how modern NLP architectures are designed, with a summary of the Apache Foundation's Unstructured Information Management Architecture. We finally consider possible future directions for NLP, and reflect on the possible impact of IBM Watson on the medical field.

The three systems perform three key steps in clinical information extraction: (1) extraction of medical problems, tests, and treatments, from discharge summaries and progress notes; (2) classification of assertions made on the medical problems; (3) classification of relations between medical concepts. Machine learning systems performed these tasks using large-dimensional bags of features, as derived from both the text itself and from external sources: UMLS, cTAKES, and Medline.

Performance was measured per subtask, using micro-averaged F-scores, as calculated by comparing system annotations with ground-truth annotations on a test set.

The systems ranked high among all submitted systems in the competition, with the following F-scores: concept extraction 0.8523 (ranked first); assertion detection 0.9362 (ranked first); relationship detection 0.7313 (ranked second).

For all tasks, we found that the introduction of a wide range of features was crucial to success. Importantly, our choice of machine learning algorithms allowed us to be versatile in our feature design, and to introduce a large number of features without overfitting and without encountering computing-resource bottlenecks.

A combination of machine learning (conditional random field and maximum entropy) and rule-based (pattern matching) techniques was used to detect negation, speculation, and hypothetical and conditional information, as well as information associated with persons other than the patient.

The best submission obtained an overall micro-averaged F-score of 0.9343.

Using semantic attributes of concepts and information about document structure as features for statistical classification of assertions is a good way to leverage rule-based and statistical techniques. In this task, the choice of features may be more important than the choice of classifier algorithm.

The authors used two machine-learning (ML) classifiers: support vector machines (SVMs) and conditional random fields (CRFs). Because SVMs and CRFs can operate on a large set of features extracted from both clinical texts and external resources, the authors address the following research question: Which features need to be selected for obtaining optimal results? To this end, the authors devise feature-selection techniques which greatly reduce the amount of manual experimentation and improve performance.

The authors evaluated their approaches on the 2010 i2b2/VA challenge data. Concept extraction achieves 79.59 micro F-measure. Assertion classification achieves 93.94 micro F-measure.

Approaching medical concept extraction and assertion classification through ML-based techniques has the advantage of easily adapting to new data sets and new medical informatics tasks. However, ML-based techniques perform best when optimal features are selected. By devising promising feature-selection techniques, the authors obtain results that outperform the current state of the art.

This paper presents two ML-based approaches for processing language in the clinical texts evaluated in the 2010 i2b2/VA challenge. By using novel feature-selection methods, the techniques presented in this paper are unique among the i2b2 participants.

A pipeline system was developed for clinical natural language processing that includes a proofreading process, with gold-standard reflexive validation and correction. The information extraction system is a combination of a machine learning approach and a rule-based approach. The outputs of this system are used for evaluation in all three tiers of the fourth i2b2/VA shared-task and workshop challenge.

Overall concept classification attained an F-score of 83.3% against a baseline of 77.0%, the optimal F-score for assertions about the concepts was 92.4% and relation classifier attained 72.6% for relationships between clinical concepts against a baseline of 71.0%. Micro-average results for the challenge test set were 81.79%, 91.90% and 70.18%, respectively.

The challenge in the multi-task test requires a distribution of time and work load for each individual task so that the overall performance evaluation on all three tasks would be more informative rather than treating each task assessment as independent. The simplicity of the model developed in this work should be contrasted with the very large feature space of other participants in the challenge who only achieved slightly better performance. There is a need to charge a penalty against the complexity of a model as defined in message minimalisation theory when comparing results.

A complete pipeline system for constructing language processing models that can be used to process multiple practical detection tasks of language structures of clinical records is presented.

We used BioTagger-GM to train machine learning taggers, which we originally developed for the detection of gene/protein names in the biology domain. Trained taggers were evaluated using the annotated clinical documents made available in the 2010 i2b2/VA Challenge workshop, consisting of documents from four data sources.

As expected, performance of a tagger trained on one data source degraded when evaluated on another source, but the degradation of the performance varied depending on data sources. A tagger trained on multiple data sources was robust, and it achieved an F score as high as 0.890 on one data source. The results also suggest that performance of machine learning taggers is likely to improve if more annotated documents are available for training.

Our study shows how the performance of machine learning taggers is degraded when they are ported across clinical documents from different sources. The portability of taggers can be enhanced by training on datasets from multiple sources. The study also shows that BioTagger-GM can be easily extended to detect clinical concept mentions with good performance.

The authors'approaches rely on both rule-based and machine-learning methods. Natural language processing is used to extract features from the input texts; these features are then used in the authors' machine-learning approaches. The authors used Conditional Random Fields for concept extraction, and Support Vector Machines for assertion and relation annotation. Depending on the task, the authors tested various combinations of rule-based and machine-learning methods.

The authors'assertion annotation system obtained an F-measure of 0.931, ranking fifth out of 21 participants at the i2b2/VA 2010 challenge. The authors' relation annotation system ranked third out of 16 participants with a 0.709 F-measure. The 0.773 F-measure the authors obtained on concept extraction did not make it to the top 10.

On the one hand, the authors confirm that the use of only machine-learning methods is highly dependent on the annotated training data, and thus obtained better results for well-represented classes. On the other hand, the use of only a rule-based method was not sufficient to deal with new types of data. Finally, the use of hybrid approaches combining machine-learning and rule-based approaches yielded higher scores.

A single support vector machine classifier was used to identify relations between concepts and to assign their semantic type. Several resources such as Wikipedia, WordNet, General Inquirer, and a relation similarity metric inform the classifier.

The techniques reported in this paper were evaluated in the 2010 i2b2 Challenge and obtained the highest F1 score for the relation extraction task. When gold standard data for concepts and assertions were available, F1 was 73.7, precision was 72.0, and recall was 75.3. F1 is defined as 2*Precision*Recall/(Precision+Recall). Alternatively, when concepts and assertions were discovered automatically, F1 was 48.4, precision was 57.6, and recall was 41.7.

Although a rich set of features was developed for the classifiers presented in this paper, little knowledge mining was performed from medical ontologies such as those found in UMLS. Future studies should incorporate features extracted from such knowledge sources, which we expect to further improve the results. Moreover, each relation discovery was treated independently. Joint classification of relations may further improve the quality of results. Also, joint learning of the discovery of concepts, assertions, and relations may also improve the results of automatic relation extraction.

Lexical and contextual features proved to be very important in relation extraction from medical texts. When they are not available to the classifier, the F1 score decreases by 3.7%. In addition, features based on similarity contribute to a decrease of 1.1% when they are not available.

The authors implemented a machine-learning-based named entity recognition system for clinical text and systematically evaluated the contributions of different types of features and ML algorithms, using a training corpus of 349 annotated notes. Based on the results from training data, the authors developed a novel hybrid clinical entity extraction system, which integrated heuristic rule-based modules with the ML-base named entity recognition module. The authors applied the hybrid system to the concept extraction and assertion classification tasks in the challenge and evaluated its performance using a test data set with 477 annotated notes.

Standard measures including precision, recall, and F-measure were calculated using the evaluation script provided by the Center of Informatics for Integrating Biology and the Bedside/VA challenge organizers. The overall performance for all three types of clinical entities and all six types of assertions across 477 annotated notes were considered as the primary metric in the challenge.

Systematic evaluation on the training set showed that Conditional Random Fields outperformed Support Vector Machines, and semantic information from existing natural-language-processing systems largely improved performance, although contributions from different types of features varied. The authors' hybrid entity extraction system achieved a maximum overall F-score of 0.8391 for concept extraction (ranked second) and 0.9313 for assertion classification (ranked fourth, but not statistically different than the first three systems) on the test data set in the challenge.

A ‘learn by example’ approach combines features derived from open-source NLP pipelines with open-source machine learning classifiers to automatically and iteratively evaluate top-performing configurations. The Fourth i2b2/VA Shared Task Challenge's concept extraction task provided the data sets and metrics used to evaluate performance.

Top F-measure scores for each of the tasks were medical problems (0.83), treatments (0.82), and tests (0.83). Recall lagged precision in all experiments. Precision was near or above 0.90 in all tasks.

With no customization for the tasks and less than 5 min of end-user time to configure and launch each experiment, the average F-measure was 0.83, one point behind the mean F-measure of the 22 entrants in the competition. Strong precision scores indicate the potential of applying the approach for more specific clinical information extraction tasks. There was not one best configuration, supporting an iterative approach to model creation.

Acceptable levels of performance can be achieved using fully automated and generalizable approaches to concept-level information extraction. The described implementation and related documentation is available for download.

The authors developed extensions to the clinical Text Analysis and Knowledge Extraction System (cTAKES) that simplify feature extraction, experimentation with various feature representations, and the development of both rule and machine-learning based document classifiers. The authors describe and evaluate their system, the Yale cTAKES Extensions (YTEX), on the classification of radiology reports that contain findings suggestive of hepatic decompensation.

The F₁-Score of the system for the retrieval of abdominal radiology reports was 96%, and was 79%, 91%, and 95% for the presence of liver masses, ascites, and varices, respectively. The authors released YTEX as open source, available at http://code.google.com/p/ytex.

The authors evaluated two well-known ASR systems on spoken clinical questions: Nuance Dragon (both generic and medical versions: Nuance Gen and Nuance Med) and the SRI Decipher (the generic version SRI Gen). The authors also explored language model adaptation using more than 4000 clinical questions to improve the SRI system's performance, and profile training to improve the performance of the Nuance Med system. The authors reported the results with the NIST standard word error rate (WER) and further analyzed error patterns at the semantic level.

Nuance Gen and Med systems resulted in a WER of 68.1% and 67.4% respectively. The SRI Gen system performed better, attaining a WER of 41.5%. After domain adaptation with a language model, the performance of the SRI system improved 36% to a final WER of 26.7%.

Without modification, two well-known ASR systems do not perform well in interpreting spoken clinical questions. With a simple domain adaptation, one of the ASR systems improved significantly on the clinical question task, indicating the importance of developing domain/genre-specific ASR systems.

We selected 6034 VAERS reports for H1N1 vaccine that were classified by medical officers as potentially positive (N_pos=237) or negative for anaphylaxis. We created a categorized corpus of text files that included the class label and the symptom text field of each report. A validation set of 1100 labeled text files was also used. Text mining techniques were applied to extract three feature sets for important keywords, low- and high-level patterns. A rule-based classifier processed the high-level feature representation, while several machine learning classifiers were trained for the remaining two feature representations.

Classifiers' performance was evaluated by macro-averaging recall, precision, and F-measure, and Friedman's test; misclassification error rate analysis was also performed.

Rule-based classifier, boosted trees, and weighted support vector machines performed well in terms of macro-recall, however at the expense of a higher mean misclassification error rate. The rule-based classifier performed very well in terms of average sensitivity and specificity (79.05% and 94.80%, respectively).

Our validated results showed the possibility of developing effective medical text classifiers for VAERS reports by combining text mining with informative feature selection; this strategy has the potential to reduce reviewer workload considerably.

We developed and tested a near-real time computerized alert system, the septic shock sniffer, based on established severe sepsis/septic shock diagnostic criteria. A sniffer scanned patients' data in the electronic medical records and notified the research coordinator on call through an institutional paging system of potentially eligible patients.

The performance of the septic shock sniffer was assessed.

The septic shock sniffer performed well with a positive predictive value of 34%. Electronic screening doubled enrollment, with 68 of 4460 ICU admissions enrolled during the 9 months after implementation versus 37 of 4149 ICU admissions before sniffer implementation (p<0.05). Efficiency was limited by study coordinator availability (not available at nights or weekends).

Automated electronic medical records screening improves the efficiency of enrollment and should be a routine tool for the recruitment of patients into time sensitive clinical trials in the ICU setting.

We parsed the Sig strings from a sample of 20 161 de-identified ambulatory e-prescriptions into variables representing the fields of the Structured and Codified Sig Format. A stratified random sample of these representations was then reviewed by a group of experts. For codified Sig fields, we attempted to map the actual words used by prescribers to the equivalent terms in the designated terminology.

Proportion of prescriptions that the Format could fully represent; proportion of terms used that could be mapped to the designated terminology.

The fields defined in the Format could fully represent 95% of Sigs (95% CI 93% to 97%), but ambiguities were identified, particularly in representing multiple-step instructions. The terms used by prescribers could be codified for only 60% of dose delivery methods, 84% of dose forms, 82% of vehicles, 95% of routes, 70% of sites, 33% of administration timings, and 93% of indications.

The findings are based on a retrospective sample of ambulatory prescriptions derived mostly from primary care physicians.

The fields defined in the Format could represent most of the patient instructions in a large prescription sample, but prior to its mandatory adoption, further work is needed to ensure that potential ambiguities are addressed and that a complete set of terms is available for the codified fields.

Forty practicing physicians, presented with standardized treatment and diagnosis questions and one question of their choosing, entered search terms which were processed in a random, blinded fashion through PubMed alone and PubMed Clinical Queries. Participants rated search retrievals for applicability to the question at hand and satisfaction.

For treatment, the primary outcome of retrieval of relevant articles was not significantly different between the groups, but a higher proportion of articles from the Clinical Queries searches met methodologic criteria (p=0.049), and more articles were published in core internal medicine journals (p=0.056). For diagnosis, the filtered results returned more relevant articles (p=0.031) and fewer irrelevant articles (overall retrieval less, p=0.023); participants needed to screen fewer articles before arriving at the first relevant citation (p<0.05). Relevance was also influenced by content terms used by participants in searching. Participants varied greatly in their search performance.

Clinical Queries filtered searches returned more high-quality studies, though the retrieval of relevant articles was only statistically different between the groups for diagnosis questions.

Retrieving clinically important research studies from Medline is a challenging task for physicians. Methodological search filters can improve search retrieval.

Unlike previous methods for automatic MeSH term assignment, we reformulate the indexing task as a ranking problem such that relevant MeSH headings are ranked higher than those irrelevant ones. Specifically, for each document we retrieve 20 neighbor documents, obtain a list of MeSH main headings from neighbors, and rank the MeSH main headings using ListNet–a learning-to-rank algorithm. We trained our algorithm on 200 documents and tested on a previously used benchmark set of 200 documents and a larger dataset of 1000 documents.

Tested on the benchmark dataset, our method achieved a precision of 0.390, recall of 0.712, and mean average precision (MAP) of 0.626. In comparison to the state of the art, we observe statistically significant improvements as large as 39% in MAP (p-value <0.001). Similar significant improvements were also obtained on the larger document set.

Experimental results show that our approach makes the most accurate MeSH predictions to date, which suggests its great potential in making a practical impact on MeSH indexing. Furthermore, as discussed the proposed learning framework is robust and can be adapted to many other similar tasks beyond MeSH indexing in the biomedical domain. All data sets are available at: http://www.ncbi.nlm.nih.gov/CBBresearch/Lu/indexing.

MEDLINE citations published between 1949 and September 2009 were retrieved if they mentioned one of 38 drugs and one of 55 AEs. A statistical document classifier (using MeSH index terms) was constructed to remove irrelevant articles unlikely to test whether a drug caused an AE. The remaining relevant articles were analyzed using a disproportionality analysis that identified drug–AE associations (signals of disproportionate reporting) using step-up procedures developed to control the familywise type I error rate.

Sensitivity and positive predictive value (PPV) for empirical drug–AE associations as judged against drug–AE associations subject to FDA warnings.

In testing, the statistical document classifier identified relevant articles with 81% sensitivity and 87% PPV. Using data filtered by the statistical document classifier, base-case models showed 64.9% sensitivity and 42.4% PPV for detecting FDA warnings. Base-case models discovered 54% of all detected FDA warnings using literature published before warnings. For example, the rofecoxib–heart disease association was evident using literature published before 2002. Analyses incorporating literature mentioning AEs common to the drug class of interest yielded 71.4% sensitivity and 40.7% PPV.

Results from large-scale literature retrieval and analysis (literature mining) compared favorably with and could complement current drug safety methods.

Since 2007, a collaborative effort to achieve clinical data sharing has been carried out at Zhejiang University in China and Kyoto University and Miyazaki University in Japan; each is running a regional clinical information center.

An international layer system named Global Dolphin was constructed with several key services, sharing patients' health information between countries using a medical markup language (MML). The system was piloted with 39 test patients.

The three regions above have records for 966 000 unique patients, which are available through Global Dolphin. Data exchanged successfully from Japan to China for the 39 study patients include 1001 MML files and 152 images. The MML files contained 197 free text-type paragraphs that needed human translation.

The pilot test in Global Dolphin demonstrates that patient information can be shared across countries through international health data exchange. To achieve cross-border sharing of clinical data, some key issues had to be addressed: establishment of a super directory service across countries; data transformation; and unique one—language translation. Privacy protection was also taken into account. The system is now ready for live use.

The project demonstrates a means of achieving worldwide accessibility of medical data, by which the integrity and continuity of patients' health information can be maintained.

We used a mixed-method analysis, consisting of cross-sectional audit log data, semi-structured interviews, and direct observation in a sample of emergency departments and ambulatory safety net clinics actively using HIE. For each site, we measured overall usage trends, user logon statistics, and data types accessed by users. We also assessed reasons for use and outcomes of use.

Overall, users accessed HIE for 6.8% of all encounters, with higher rates of access for repeat visits, for patients with comorbidities, for patients known to have data in the exchange, and at sites providing HIE access to both nurses and physicians. Discharge summaries and test reports were the most frequently accessed data in the exchange. Providers consistently noted retrieving additional history, preventing repeat tests, comparing new results to retrieved results, and avoiding hospitalizations as a consequence of HIE access.

HIE use in emergency departments and ambulatory clinics was focused on patients where missing information was believed to be present in the exchange and was related to factors including the roles of people with access, the setting, and other site-specific issues that impacted the overall breadth of routine system use. These data should form an important foundation as other sites embark upon HIE implementation.

Using neurosurgery inpatient visit data from EUH and GMH, unique patients who visited both hospitals were identified through classification by name and age at time of visit. The frequency of flow patterns, including time between visits, and the statistical significance of crossover rates for patients with particular diagnoses were determined.

The time between visits, flow patterns, and proportion of patients exhibiting crossover behavior were calculated for the total population studied as well as subpopulations.

5.25% of patients having multiple visits over the study period visited the neurosurgical departments at both hospitals. 77% of crossover patients visited the level 1 trauma center (GMH) before visiting EUH.

The true patient crossover may be under-estimated because the study population only consists of neurosurgical inpatients at EUH and GMH.

We demonstrate that detailed analysis of crossover behavior provides a deeper understanding of the potential value of HIE.

We analyzed the commonalities and divergences of empirical studies published 1990–2010 that have applied the T&M approach to examine the impact of health IT implementation on clinical work processes and workflow. The analysis led to the development of a suggested ‘checklist’ intended to help future T&M research produce compatible and comparable results. We call this checklist STAMP (Suggested Time And Motion Procedures).

STAMP outlines a minimum set of 29 data/ information elements organized into eight key areas, plus three supplemental elements contained in an ‘Ancillary Data’ area, that researchers may consider collecting and reporting in their future T&M endeavors.

T&M is generally regarded as the most reliable approach for assessing the impact of health IT implementation on clinical work. However, there exist considerable inconsistencies in how previous T&M studies were conducted and/or how their results were reported, many of which do not seem necessary yet can have a significant impact on quality of research and generalisability of results. Therefore, we deem it is time to call for standards that can help improve the consistency of T&M research in health informatics. This study represents an initial attempt.

We developed a suggested checklist to improve the methodological and results reporting consistency of T&M research, so that meaningful insights can be derived from across-study synthesis and health informatics, as a field, will be able to accumulate knowledge from these studies.

We conducted a cross-sectional survey of individuals given access to the HIE at participating organizations and examined some of the usability and usage factors related to the technology acceptance model.

We probed user perceptions using the Questionnaire for User Interaction Satisfaction, an author-generated Trust scale, and user characteristic questions (eg, age, weekly system usage time).

Overall, users viewed the system favorably (ratings for all usability items were greater than neutral (one-sample Wilcoxon test, p<0.0014, Bonferroni-corrected for 35 tests). System usage was regressed on usability, trust, and demographic and user characteristic factors. Three usability factors were positively predictive of system usage: overall reactions (p<0 0.01), learning (p<0.05), and system functionality (p<0.01). Although trust is an important component in collaborative relationships, we did not find that user trust of other participating healthcare entities was significantly predictive of usage. An analysis of respondents' comments revealed ways to improve the HIE.

We used a rapid deployment model to develop an HIE and found that perceptions of system usability were positive. We also found that system usage was predicted well by some aspects of usability. Results from this study suggest that a rapid development approach may serve as a viable model for developing usable HIEs serving communities with limited resources.

This model-averaged naive Bayes (MANB) method was applied to predict late onset Alzheimer's disease in 1411 individuals who each had 312 318 SNP measurements available as genome-wide predictive features. Its performance was compared to that of a naive Bayes algorithm without feature selection (NB) and with feature selection (FSNB).

Performance of each algorithm was measured in terms of area under the ROC curve (AUC), calibration, and run time.

The training time of MANB (16.1 s) was fast like NB (15.6 s), while FSNB (1684.2 s) was considerably slower. Each of the three algorithms required less than 0.1 s to predict the outcome of a test case. MANB had an AUC of 0.72, which is significantly better than the AUC of 0.59 by NB (p<0.00001), but not significantly different from the AUC of 0.71 by FSNB. MANB was better calibrated than NB, and FSNB was even better in calibration. A limitation was that only one dataset and two comparison algorithms were included in this study.

MANB performed comparatively well in predicting a clinical outcome from a high-dimensional genome-wide dataset. These results provide support for including MANB in the methods used to predict outcomes from large, genome-wide datasets.

The authors mapped phenotype data dictionaries from five different eMERGE (Electronic Medical Records and Genomics) Network sites studying multiple diseases such as peripheral arterial disease and type 2 diabetes. For mapping, standardized terminological and metadata repository resources, such as the caDSR (Cancer Data Standards Registry and Repository) and SNOMED CT (Systematized Nomenclature of Medicine), were used. The mapping process comprised both lexical (via searching for relevant pre-coordinated concepts and data elements) and semantic (via post-coordination) techniques. Where feasible, new data elements were curated to enhance the coverage during mapping. A web-based application was also developed to uniformly represent and query the mapped data elements from different eMERGE studies.

Approximately 60% of the target data elements (95 out of 157) could be mapped using simple lexical analysis techniques on pre-coordinated terms and concepts before any additional curation of terminology and metadata resources was initiated by eMERGE investigators. After curation of 54 new caDSR CDEs and nine new NCI thesaurus concepts and using post-coordination, the authors were able to map the remaining 40% of data elements to caDSR and SNOMED CT. A web-based tool was also implemented to assist in semi-automatic mapping of data elements.

This study emphasizes the requirement for standardized representation of clinical research data using existing metadata and terminology resources and provides simple techniques and software for data element mapping using experiences from the eMERGE Network.

A manually validated warfarin pharmacogenetic study identified a cohort of 1125 patients with a stable warfarin dose, in which 776 patients were managed by Coumadin Clinic physicians, and the remaining 349 patients were managed by their providers. The authors developed two algorithms to extract weekly warfarin doses from both data sets: a regular expression-based program for semistructured Coumadin Clinic notes; and an advanced weekly dose calculator based on an existing medication information extraction system (MedEx) for narrative providers' notes. The authors then conducted an association analysis between an automatically extracted stable weekly dose of warfarin and four genetic variants of VKORC1 and CYP2C9 genes. The performance of the weekly dose-extraction program was evaluated by comparing it with a gold standard containing manually curated weekly doses. Precision, recall, F-measure, and overall accuracy were reported. Associations between known variants in VKORC1 and CYP2C9 and warfarin stable weekly dose were performed with linear regression adjusted for age, gender, and body mass index.

The authors' evaluation showed that the MedEx-based system could determine patients' warfarin weekly doses with 99.7% recall, 90.8% precision, and 93.8% accuracy. Using the automatically extracted weekly doses of warfarin, the authors successfully replicated the previous known associations between warfarin stable dose and genetic variants in VKORC1 and CYP2C9.

The authors statistically prioritized common interactors between established cancer genes and genes from each prostate cancer signature of poor prognosis independently via a previously validated single protein analysis of network (SPAN) methodology. Additionally, they computationally identified pathways among the aggregated interactors across signatures and validated them using a similarity metric and patient survival.

Using an information-theoretic metric, the authors assessed the mechanistic similarity of the interactor signature. Its prognostic ability was assessed in an independent cohort of 198 patients with high-Gleason prostate cancer using Kaplan–Meier analysis.

Of the 13 prostate cancer signatures that were evaluated, eight interacted significantly with established cancer genes (false discovery rate <5%) and generated a 42-gene interactor signature that showed the highest mechanistic similarity (p<0.0001). Via parameter-free unsupervised classification, the interactor signature dichotomized the independent prostate cancer cohort with a significant survival difference (p=0.009). Interpretation of the network not only recapitulated phosphatidylinositol-3 kinase/NF-B signaling, but also highlighted less well established relevant pathways such as the Janus kinase 2 cascade.

SPAN methodolgy provides a robust means of abstracting disparate prostate cancer gene expression signatures into clinically useful, prioritized pathways as well as useful mechanistic pathways.

The experimental evaluation shows that: (1) ImageMiner is able to support reliable detection and feature extraction of tumor regions within imaged tissues; (2) images and analysis results managed in ImageMiner can be searched for and retrieved on the basis of image-based features, classification information, and any correlated clinical data, including any metadata that have been generated to describe the specified tissue and TMA; and (3) the system is able to reduce computation time of analyses by exploiting computing clusters, which facilitates analysis of larger sets of tissue samples.

BIRN tools are grouped into ‘capabilities’ and are available in the areas of data management, data security, information integration, and knowledge engineering. BIRN has a user-driven focus and employs a layered architectural approach that promotes reuse of infrastructure. BIRN tools are designed to be modular and therefore can work with pre-existing tools. BIRN users can choose the capabilities most useful for their application, while not having to ensure that their project conforms to a monolithic architecture.

BIRN has implemented a new software-based data-sharing infrastructure that has been put to use in many different domains within biomedicine. BIRN is actively involved in outreach to the broader biomedical community to form working partnerships.

BIRN's mission is to provide capabilities and services related to data sharing to the biomedical research community. It does this by forming partnerships and solving specific, user-driven problems whose solutions are then available for use by other groups.

Articles were linked to the grants they acknowledge using the grant acknowledgment strings in PubMed using a parsing and matching process as embodied in the NIH Scientific Publication Information Retrieval & Evaluation System system. Additional data from PubMed and citation counts from Scopus were added to the linkage data. The data comprise 2 572 576 records from 1980 to 2009.

The data show that synergies between NIH institutes are increasing over time; 29% of current articles acknowledge grants from multiple institutes. The median time lag to publication for a new grant is 3 years. Each grant contributes to approximately 1.7 articles per year, averaged over all grant types. Articles acknowledging US Public Health Service (PHS, which includes NIH) funding are cited twice as much as US-authored articles acknowledging no funding source. Articles acknowledging both PHS funding and a non-US government funding source receive on average 40% more citations that those acknowledging PHS funding sources alone.

The US PHS is effective at funding research with a higher-than-average impact. The data are amenable to further and much more detailed analysis.

The hierarchies for concepts in the Core Problem List Subset published by the Unified Medical Language System were examined for their appropriateness in two applications. Anomalies were traced to their source to determine whether they were simple local errors, systematic inferences propagated by SNOMED's classification process, or the result of problems with SNOMED's schemas. Conclusions were confirmed by showing that altering the root cause and reclassifying had the intended effects, and not others.

Major problems were encountered, involving concepts central to medicine including myocardial infarction, diabetes, and hypertension. Most of the issues raised were systematic. Some exposed fundamental errors in SNOMED's schemas, particularly with regards to anatomy. In many cases, the root cause could only be identified and corrected with the aid of a classifier.

This is a preliminary ‘experiment of opportunity.’ The results are not exhaustive; nor is consensus on all points definitive.

The SNOMED CT hierarchies cannot be relied upon in their present state in our applications. However, systematic quality assurance and correction are possible and practical but require sound techniques analogous to software engineering and combined lexical and semantic techniques. Until this is done, anyone using SNOMED codes should exercise caution. Errors in the hierarchies, or attempts to compensate for them, are likely to compromise interoperability and meaningful use.

Built on the idea of a normalized name for a medication at a given level of abstraction, RxNorm provides a set of names and relationships based on 11 different external source vocabularies. The standard model enables decision support to take place for a variety of uses at the appropriate level of abstraction. With the incorporation of National Drug File Reference Terminology (NDF-RT) from the Veterans Administration, even more sophisticated decision support has become possible.

While related products such as RxTerms, RxNav, MyMedicationList, and MyRxPad have been recognized as helpful for various uses, tasks such as identifying exactly what is and is not on the market remain a challenge.

The collaborative filtering approach presented in this paper emerges from the insight that an omission in a medication list is analogous to an item a consumer might purchase from a product list. Online retailers use collaborative filtering to recommend relevant products using retrospective purchase data. In this article, the authors argue that patient information in electronic medical records, combined with artificial intelligence methods, can enhance medication reconciliation. The authors formulate the detection of omissions in medication lists as a collaborative filtering problem. Detection of omissions is accomplished using several machine-learning approaches. The effectiveness of these approaches is evaluated using medication data from three long-term care centers. The authors also propose several decision-theoretic extensions to the methodology for incorporating medical knowledge into recommendations.

Results show that collaborative filtering identifies the missing drug in the top-10 list about 40–50% of the time and the therapeutic class of the missing drug 50%–65% of the time at the three clinics in this study.

Results suggest that collaborative filtering can be a valuable tool for reconciling medication lists, complementing currently recommended process-driven approaches. However, a one-size-fits-all approach is not optimal, and consideration should be given to context (eg, types of patients and drug regimens) and consequence (eg, the impact of omission on outcomes).

A standard methodology for annotation guideline development, gold standard annotations, and inter-annotator agreement (IAA) was used.

The gold standard annotations resulted in 7214 markables, 5992 pairs, and 1304 chains. Each report averaged 40 anaphoric markables, 33 pairs, and seven chains. The overall IAA is high on the Mayo dataset (0.6607), and moderate on the University of Pittsburgh Medical Center (UPMC) dataset (0.4072). The IAA between each annotator and the gold standard is high (Mayo: 0.7669, 0.7697, and 0.9021; UPMC: 0.6753 and 0.7138). These results imply a quality corpus feasible for system development. They also suggest the complementary nature of the annotations performed by the experts and the importance of an annotator team with diverse knowledge backgrounds.

Only one of the annotators had the linguistic background necessary for annotation of the linguistic attributes. The overall generalizability of the guidelines will be further strengthened by annotations of data from additional sites. This will increase the overall corpus size and the representation of each relation type.

The first step toward the development of an anaphoric relation resolver as part of a comprehensive natural language processing system geared specifically for the clinical narrative in the electronic medical record is described. The deidentified annotated corpus will be available to researchers.

Study phase 1 applied four aberrancy detection algorithms (CUSUM, EWMA, space-time scan statistic, and WSARE) to retrospective microbiologic culture data, producing a list of past candidate outbreak clusters. In phase 2, four infectious disease physicians categorized the phase 1 algorithm-identified clusters to ascertain algorithm performance. In phase 3, project members combined the algorithms to create a unified screening system and conducted a retrospective pilot evaluation.

The study calculated recall and precision for each algorithm, and created precision-recall curves for various methods of combining the algorithms into a unified screening tool.

Individual algorithm recall and precision ranged from 0.21 to 0.31 and from 0.053 to 0.29, respectively. Few candidate outbreak clusters were identified by more than one algorithm. The best method of combining the algorithms yielded an area under the precision-recall curve of 0.553. The phase 3 combined system detected all infection control-confirmed outbreaks during the retrospective evaluation period.

Lack of phase 2 reviewers' agreement indicates that subjective expert review was an imperfect gold standard. Less conservative filtering of culture results and alternate parameter selection for each algorithm might have improved algorithm performance.

Hospital outbreak detection presents different challenges than traditional syndromic surveillance. Nevertheless, algorithms developed for syndromic surveillance have potential to form the basis of a combined system that might perform clinically useful hospital outbreak screening.

The authors gathered health-promotion materials in English from local and national public-health websites. Spanish versions were created by translating the documents using a freely available machine-translation website. Translations were rated for adequacy and fluency, analyzed for errors, manually corrected by a human posteditor, and compared with exclusively manual translations.

Machine translation plus postediting took 15–53 min per document, compared to the reported days or even weeks for the standard translation process. A blind comparison of machine-assisted and human translations of six documents revealed overall equivalency between machine-translated and manually translated materials. The analysis of translation errors indicated that the most important errors were word-sense errors.

The results indicate that machine translation plus postediting may be an effective method of producing multilingual health materials with equivalent quality but lower cost compared to manual translations.

We built a logistic regression model to predict alert acceptance of drug–drug interaction (DDI) alerts in three different settings. Ten variables from the clinical and human factors literature were evaluated as potential modulators of provider alert acceptance. ORs were calculated for the impact of knowledge quality, alert display, textual information, prioritization, setting, patient age, dose-dependent toxicity, alert frequency, alert level, and required acknowledgment on acceptance of the DDI alert.

50 788 DDI alerts were analyzed. Providers accepted only 1.4% of non-interruptive alerts. For interruptive alerts, user acceptance positively correlated with frequency of the alert (OR 1.30, 95% CI 1.23 to 1.38), quality of display (4.75, 3.87 to 5.84), and alert level (1.74, 1.63 to 1.86). Alert acceptance was higher in inpatients (2.63, 2.32 to 2.97) and for drugs with dose-dependent toxicity (1.13, 1.07 to 1.21). The textual information influenced the mode of reaction and providers were more likely to modify the prescription if the message contained detailed advice on how to manage the DDI.

We evaluated potential modulators of alert acceptance by assessing content and human factors issues, and quantified the impact of a number of specific factors which influence alert acceptance. This information may help improve clinical decision support systems design.

Children between 0 and 11 years were randomized by the CHICA system. In the intervention group, parents were asked about TB and iron-deficiency risk, and physicians received a tailored prompt. In the control group, no screens were performed, and the physician received a generic prompt about these disorders.

1123 participants were randomized to the control group and 1116 participants to the intervention group. Significantly more people reported positive risk factors for iron-deficiency anemia in the intervention group (17.5% vs 3.1%, OR 6.6, 95% CI 4.5 to 9.5). In general, far fewer parents reported risk factors for TB than for iron-deficiency anemia. Again, there were significantly higher detection rates of positive risk factors in the intervention group (1.8% vs 0.8%, OR 2.3, 95% CI 1.0 to 5.0).

It is possible that there may be more positive screens without improving outcomes. However, the guidelines are based on studies that have evaluated the questions the authors used as sensitive and specific, and there is no reason to believe that parents misunderstood them.

Many screening tests are risk-based, not universal, leaving physicians to determine who should have a further workup. This can be a time-consuming process. The authors demonstrated that the CHICA system performs well in assessing risk automatically for TB and iron-deficiency anemia.

Retrospective analysis of inpatient adverse drug events (ADEs) and hospital-associated infections (HAIs) detected by either a computerized surveillance system (CSS) or manual chart review (MCR).

Descriptive analysis of events detected using the two methods by type of AE, type of information about the AE, and sources of the information.

CSS detected more HAIs than MCR (92% vs 34%); however, a similar number of ADEs was detected by both systems (52% vs 51%). The agreement between systems was greater for HAIs than ADEs (26% vs 3%). The CSS missed events that did not have information in coded format or that were described only in physician narratives. The MCR detected events missed by CSS using information in physician narratives. Discharge summaries were more likely to contain information about AEs than any other type of physician narrative, followed by emergency department reports for HAIs and general consult notes for ADEs. Some ADEs found by MCR were detected by CSS but not verified by a clinician.

Inability to distinguish between CSS false positives and suspected AEs for cases in which the clinician did not document their assessment in the CSS.

The effect that information source has on different surveillance methods depends on the type of AE. Integrating information from physician narratives with CSS using natural language processing would improve the detection of ADEs more than HAIs.

From EHR access logs and other organizational data collected over a 2-month period, the authors extracted 26 features likely to be useful in detecting suspicious accesses. Selected events were marked as either suspicious or appropriate by privacy officers, and served as the gold standard set for model evaluation. The authors trained logistic regression (LR) and support vector machine (SVM) models on 10-fold cross-validation sets of 1291 labeled events. The authors evaluated the sensitivity of final models on an external set of 58 events that were identified as truly inappropriate and investigated independently from this study using standard operating procedures.

The area under the receiver operating characteristic curve of the models on the whole data set of 1291 events was 0.91 for LR, and 0.95 for SVM. The sensitivity of the baseline model on this set was 0.8. When the final models were evaluated on the set of 58 investigated events, all of which were determined as truly inappropriate, the sensitivity was 0 for the baseline method, 0.76 for LR, and 0.79 for SVM.

The LR and SVM models may not generalize because of interinstitutional differences in organizational structures, applications, and workflows. Nevertheless, our approach for constructing the models using statistical and machine-learning techniques can be generalized. An important limitation is the relatively small sample used for the training set due to the effort required for its construction.

The results suggest that statistical and machine-learning methods can play an important role in helping privacy officers detect suspicious accesses to EHRs.