New Unintended Adverse Consequences of Electronic Health Records.

Although the health information technology industry has made considerable progress in the design, development, implementation, and use of electronic health records (EHRs), the lofty expectations of the early pioneers have not been met. In 2006, the Provider Order Entry Team at Oregon Health & Science University described a set of unintended adverse consequences (UACs), or unpredictable, emergent problems associated with computer-based provider order entry implementation, use, and maintenance. Many of these originally identified UACs have not been completely addressed or alleviated, some have evolved over time, and some new ones have emerged as EHRs became more widely available. The rapid increase in the adoption of EHRs, coupled with the changes in the types and attitudes of clinical users, has led to several new UACs, specifically: complete clinical information unavailable at the point of care; lack of innovations to improve system usability leading to frustrating user experiences; inadvertent disclosure of large amounts of patient-specific information; increased focus on computer-based quality measurement negatively affecting clinical workflows and patient-provider interactions; information overload from marginally useful computer-generated data; and a decline in the development and use of internally-developed EHRs. While each of these new UACs poses significant challenges to EHR developers and users alike, they also offer many opportunities. The challenge for clinical informatics researchers is to continue to refine our current systems while exploring new methods of overcoming these challenges and developing innovations to improve EHR interoperability, usability, security, functionality, clinical quality measurement, and information summarization and display.

Clinical Decision Support: a 25 Year Retrospective and a 25 Year Vision.

OBJECTIVE: The objective of this review is to summarize the state of the art of clinical decision support (CDS) circa 1990, review progress in the 25 year interval from that time, and provide a vision of what CDS might look like 25 years hence, or circa 2040. METHOD: Informal review of the medical literature with iterative review and discussion among the authors to arrive at six axes (data, knowledge, inference, architecture and technology, implementation and integration, and users) to frame the review and discussion of selected barriers and facilitators to the effective use of CDS. RESULT: In each of the six axes, significant progress has been made. Key advances in structuring and encoding standardized data with an increased availability of data, development of knowledge bases for CDS, and improvement of capabilities to share knowledge artifacts, explosion of methods analyzing and inferring from clinical data, evolution of information technologies and architectures to facilitate the broad application of CDS, improvement of methods to implement CDS and integrate CDS into the clinical workflow, and increasing sophistication of the end-user, all have played a role in improving the effective use of CDS in healthcare delivery. CONCLUSION: CDS has evolved dramatically over the past 25 years and will likely evolve just as dramatically or more so over the next 25 years. Increasingly, the clinical encounter between a clinician and a patient will be supported by a wide variety of cognitive aides to support diagnosis, treatment, care-coordination, surveillance and prevention, and health maintenance or wellness.

Bovine eotaxin (CCL11)--an unusual member of the eotaxin group--attracts eosinophils in vitro but is not responsible for eosinophilia in the ovary.

Under physiological conditions normally characterised by low tissue infiltration of eosinophils, a conspicuous number of these cells are attracted into the human and ruminant ovary. Eosinophils suddenly increase in the thecal layer of the preovulatory follicle and corpus luteum at very early development. Currently, we only have a limited understanding of the mechanism for the recruitment of the ovarian eosinophils. Eotaxin (CCL11) may be one of the chemoattractants involved in stimulating eosinophils to migrate selectively into ovary. As a prerequisite for the analysis of eotaxin expression in the bovine ovary, we determined the complete bovine eotaxin mRNA sequence since it was not available from databases. The bovine eotaxin is the first member of the monocyte chemoattractant protein (MCP)/eotaxin subfamily with two mRNA isoforms varying in length in the untranslated 3'-untranslated region. The unusual amino-acid sequence of bovine eotaxin contains structural features that are so far known to be characteristic for MCP, but not eotaxin. In our microchemotaxis assays, recombinant bovine eotaxin showed a functional pattern orthologous to known eotaxins. Thus, the chimeric structure of bovine eotaxin did not affect the favoured chemotactic activity on eosinophils. Semiquantitative RT-PCR was used to investigate the expression of eotaxin in different regions of the bovine ovary. We only detected faint eotaxin mRNA signals that did not indicate physiological significance even in stimulated granulosa cell cultures, follicle-derived macrophages or fibroblasts. Taken together, bovine eotaxin attracts eosinophils in vitro but is not responsible for eosinophilia in the ovary. Its unusual chimeric structure confirms the unity of the MCP/eotaxin subfamily of CC chemokines and distinguishes it from other CC chemokine subfamilies.

Prevalence and treatment costs of type 2 diabetes in Germany and the effects of social and demographical differences.

Treatment costs for type 2 diabetes account for a substantial amount of the expenses for statutory health care funds. Within a study sample of the year 2005, 6.8% of the insured were being treated for type 2 diabetes mellitus. Compared to the non-diabetic insured in the sample, patients included more males and older persons. Employed diabetics also showed lower mean gross salary when compared to the non-diabetic employed of the sample. In 2007, their mean costs for in- and outpatient care and drug prescriptions amounted to 2,622 Euros per patient. The impacts of social and demographical patient characteristics on total treatment costs were measured with a multiple linear regression model, controlling for the hypoglycemic therapy of the patient. Here, the impact of age, gender and intensive insulin therapy became evident. A higher annual salary had a negative, yet non-significant, effect.

Validation of a Crowdsourcing Methodology for Developing a Knowledge Base of Related Problem-Medication Pairs.

BACKGROUND: Clinical knowledge bases of problem-medication pairs are necessary for many informatics solutions that improve patient safety, such as clinical summarization. However, developing these knowledge bases can be challenging. OBJECTIVE: We sought to validate a previously developed crowdsourcing approach for generating a knowledge base of problem-medication pairs in a large, non-university health care system with a widely used, commercially available electronic health record. METHODS: We first retrieved medications and problems entered in the electronic health record by clinicians during routine care during a six month study period. Following the previously published approach, we calculated the link frequency and link ratio for each pair then identified a threshold cutoff for estimated problem-medication pair appropriateness through clinician review; problem-medication pairs meeting the threshold were included in the resulting knowledge base. We selected 50 medications and their gold standard indications to compare the resulting knowledge base to the pilot knowledge base developed previously and determine its recall and precision. RESULTS: The resulting knowledge base contained 26,912 pairs, had a recall of 62.3% and a precision of 87.5%, and outperformed the pilot knowledge base containing 11,167 pairs from the previous study, which had a recall of 46.9% and a precision of 83.3%. CONCLUSIONS: We validated the crowdsourcing approach for generating a knowledge base of problem-medication pairs in a large non-university health care system with a widely used, commercially available electronic health record, indicating that the approach may be generalizable across healthcare settings and clinical systems. Further research is necessary to better evaluate the knowledge, to compare crowdsourcing with other approaches, and to evaluate if incorporating the knowledge into electronic health records improves patient outcomes.

Expression and regulation of regulated on activation, normal T cells expressed and secreted in thyroid tissue of patients with Graves' disease and thyroid autonomy and in thyroid-derived cell populations.

Thyroid glands affected by Graves' disease (GD) show striking lymphocytic infiltration, mainly by CD45RO(+) T cells. The mechanisms by which the various lymphocytic subsets are recruited and maintained in the thyroid are unknown. RANTES (regulated on activation, normal T cells expressed and secreted) in interaction with its receptors (CCR1, CCR3, CCR4 and CCR5) may be one of the favorite chemokines involved in the cell trafficking and maintenance. RANTES messenger RNA (mRNA) was quantified in the thyroid tissue of 16 patients with GD and 7 patients with thyroid autonomy (TA), using competitive RT-PCR. We found a clear correlation between the RANTES mRNA level and 1) the degree of T-cell infiltration (r = 0.68), and 2) the level of serum antibodies to thyroid peroxidase (r = 0.76) in GD but not in TA patients. There was no difference between the autonomous nodules and the quiescent surrounding tissue in TA patients. To define the cellular source of RANTES mRNA and protein, we examined various thyroid-derived cells. Lymphocytes showed a markedly higher basal RANTES mRNA and protein level (mean +/- SEM; pg/mL, n = 3; 140 +/- 30) than thyrocytes (12 +/- 5) and fibroblasts (9 +/- 2). Lymphocyte stimulation with PMA enhanced RANTES secretion significantly (4490 +/- 200). Fibroblasts responded to stimulation with interleukin 1 (530 +/- 220) and tumor necrosis factor alpha (2780 +/- 1790), whereas thyrocytes did not. However, some thyroid carcinoma cell lines showed very high basal and stimulated RANTES expression. Lymphocytes expressed the mRNA of all chemokine receptors that bind RANTES. The number of CCR3(+) and CCR5(+) T cells was significantly higher in thyroid-derived leukocytes than in those in the peripheral blood stream. We conclude that RANTES expression, mainly by lymphocytes, is perhaps involved in the maintenance of lymphocytic infiltration and, therefore, in the autoimmune responses in GD.

The role of CXCR5 and its ligand CXCL13 in the compartmentalization of lymphocytes in thyroids affected by autoimmune thyroid diseases.

OBJECTIVE: Graves' disease (GD) and Hashimoto's thyroiditis (HT) are characterized by lymphocytic infiltrates partly resembling secondary lymphoid follicles in the thyroid. CXCR5 and its ligand CXCL13 regulate compartmentalization of B- and T-cells in secondary lymphoid organs. The aim of the study was to elucidate the role of this chemokine receptor-ligand pair in thyroid autoimmunity. METHODS: Peripheral blood and thyroid-derived lymphocyte subpopulations were examined by flow cytometry for CXCR5. CXCR5 and CXCL13 cDNA were quantified in thyroid tissues by real-time RT-PCR. RESULTS: We found no differences between the percentages of peripheral blood CXCR5+ T- and B-cells in GD patients (n=10) and healthy controls (n=10). In GD patients, the number of memory CD4+ cells expressing CXCR5 which are functionally characterized as follicular B helper T-cells is higher in thyroid-derived (18+/-3%) compared with peripheral blood T-lymphocytes (8+/-2%). The highest CXCL13 mRNA levels were found in HT (n=2, 86.1+/-1.2 zmol (10(-21) mol) cDNA/PCR) followed by GD tissues (n=16, 9.6+/-3.5). Only low amounts were determined in thyroid autonomy (TA) (n=11) thyroid tissues, irrespective of whether the autonomous nodule (0.5+/-0.1) or the surrounding normal tissue (1.8+/-0.7) had been analyzed. The same differences were found for CXCR5 (HT: 179.1+/-6.8; GD: 17.4+/-10.6; TA(nodule): 0.8+/-0.5; TA(normal): 4.4+/-3.6). In GD, there is a correlation between CXCL13 and CXCR5 mRNA levels and the number of focal lymphocytic infiltrates and germinal centers as well as anti-thyroperoxidase but not anti-TSH receptor autoantibodies. CONCLUSIONS: CXCR5 and CXCL13 play an essential role in maintaining B- and T-cells in lymphocytic infiltrates and ectopic follicles in thyroid tissue from patients affected by autoimmunity.

Transesophageal color flow Doppler imaging for aortic insufficiency in patients having cardiac operations.

Transesophageal color flow Doppler findings were studied in 30 patients with aortic insufficiency who had cardiac operations. Measurements were expressed as ratios of corresponding left ventricular outflow tract dimensions. Regurgitant jet proximal width ratio was significantly related to jet area ratio (r = 0.92) and correlated poorly with the degree of jet penetration into the left ventricular cavity (r = 0.32). The vectors of the regurgitant jets were variable. Nine patients had undergone aortography. Regurgitant jet proximal width and area ratios were significantly related to angiographic grade (r = 0.88 and 0.87, respectively) in these patients. We concluded that the esophagus offers a satisfactory transducer orientation for color flow Doppler assessment of aortic insufficiency.

Medical informatics on the Internet: creating the sci.med. informatics newsgroup.

A Usenet newsgroup, sci.med.informatics, has been created to serve as an international electronic forum for discussion of issues related to medical informatics. The creation process follows a set of administrative rules set out by the Usenet administration on the Internet and consists of five steps: 1) informal discussion, 2) request for formal discussion, 3) formal discussion, 4) voting, and 5) posting of results. The newsgroup can be accessed using any news reader via the Internet.

Computer-based physician order entry: the state of the art.

Direct computer-based physician order entry has been the subject of debate for over 20 years. Many sites have implemented systems successfully. Others have failed outright or flirted with disaster, incurring substantial delays, cost overruns, and threatened work actions. The rationale for physician order entry includes process improvement, support of cost-conscious decision making, clinical decision support, and optimization of physicians' time. Barriers to physician order entry result from the changes required in practice patterns, roles within the care team, teaching patterns, and institutional policies. Key ingredients for successful implementation include: the system must be fast and easy to use, the user interface must behave consistently in all situations, the institution must have broad and committed involvement and direction by clinicians prior to implementation, the top leadership of the organization must be committed to the project, and a group of problem solvers and users must meet regularly to work out procedural issues. This article reviews the peer-reviewed scientific literature to present the current state of the art of computer-based physician order entry.

Hematological concomitants of alcoholism: development and validation of a clinical screening technique.

An investigation into the use of blood chemistry variables in the identification of young adult alcoholics revealed that a combinative process utilizing 11 blood chemistry variables was superior to the use of individual measures. The investigation further validated the use of a linear discriminant analysis technique in identifying the blood chemistry measures and a discriminant function was produced that classified alcoholics and controls with a high degree of accuracy. This level of precision in prediction was maintained in validation trials on independent samples. The blood chemistry variables were extracted from a combination of commonly ordered blood tests. Results of the investigation indicate that clinical usage of the screening procedure is readily available without sophisticated computer support or exotic blood analysis.

Work-sampling: a statistical approach to evaluation of the effect of computers on work patterns in healthcare.

An increasing number of health-care institutions are in the process of implementing clinical computing systems. The need for an accurate assessment of the clinical, administrative, social, and financial effects of such systems has been recognized. Techniques have been developed to evaluate these effects on the work patterns of health-care workers including: time-motion analysis, subjective evaluations, review of departmental statistics, personal activity records, and work-sampling. This study reviews these techniques, discusses both positive and negative aspects, and presents a step-by-step description of work-sampling.

A quantitative ranking of the Biomedical Informatics serials.

We have developed a quantitative serial ranking system based on multiple citation analysis techniques, library use statistics, expert opinion, and selected distinguishing publication characteristics. Evaluation criteria categories include: average Science Citation Index (Impact Factor, Immediacy Index, Total citations) rankings from 1987 to 1992; citation source counts of multiple "core" biomedical informatics publications; a questionnaire sent to American College of Medical Informatics Fellows; publication delay; distinguishing characteristics (e.g., subscription cost, total circulation, year established, places indexed, affiliation with a professional society, major biomedical resource library holdings); and the total number of interlibrary loan requests to the U. S. National Library of Medicine. The top serials were Computers and Biomedical Research, MD Computing, Methods of Information in Medicine, Medical Decision Making and Computers in Biology and Medicine.

The multi-trellis software architecture and the intelligent cardiovascular monitor.

A real-time, intelligent cardiovascular monitor is complex. It must process multiple waveforms, recognize artifacts, extract pertinent parameters, recognize a patient's clinical state, analyze the problem and formulate a response. This paper presents the multi-trellis (a collection of process trellises), a software architecture for building such a monitor. A process trellis is a uniform hierarchical framework for heterogeneous program modules. The multi-trellis extension allows one to compile several process trellis programs with widely varying run-time requirements into a single executable program that it is efficient, predictable and usable. Our prototype consists of two process trellises. The lower trellis contains processes to analyze three different analog signals: the blood pressure from a non-invasive monitor and an arterial catheter, and the ECG. The upper trellis contains processes to help detect evolving hemodynamic trends, identify abnormalities, and present a succinct summary to the clinician. Our prototype shows that the multi-trellis is a demonstrably useful software architecture for building these real-time, intelligent monitors.

A survey of patient-provider e-mail communication: what do patients think?

Communication between patients and providers forms the backbone of the patient-provider relationship. Often such communication is strained due to time and space limitations on the part of both patients and providers. Many healthcare organizations are developing secure e-mail communication facilities to allow patients to exchange e-mail messages with their providers. Providers are worried that opening such lines of communication will inundate them with vast quantities of e-mail from their patients. Patients are worried that their messages will be intercepted and read by unauthorized people. In an attempt to determine how a group of internet-active, e-mail-ready patients currently use, or potentially view, the ability to exchange e-mail messages with their health care providers, we distributed a survey via e-mail to over 9500 patients. After determining each patient's e-mail activity level (based on the number of messages sent each day), we asked questions such as: "Have you ever sent e-mail to your provider?" "What issues or concerns have prevented you from sending e-mail messages to your provider?" "If your provider were to tell you that someone in his/her office may screen, read or perhaps reply to your message before he/she sees it, to what extent would you be concerned about this?" and "How would you rate your overall satisfaction with the use of e-mail to communicate with your provider?" Results from the survey indicate that nearly 85% of the patients surveyed send at least one e-mail message per day, but that very few (i.e. 6%) of the patients have actually sent an e-mail message to their provider. Interestingly, over half of the patients indicated that they would like to send their providers e-mail, but that they do not know their provider's e-mail address.

Using information systems to measure and improve quality.

Information systems (IS) are increasingly important for measuring and improving quality. In this paper, we describe our integrated delivery system's plan for and experiences with measuring and improving quality using IS. Our belief is that for quality measurement to be practical, it must be integrated with the routine provision of care and whenever possible should be done using IS. Thus, at one hospital, we now perform almost all quality measurement using IS. We are also building a clinical data warehouse, which will serve as a repository for quality information across the network. However, IS are not only useful for measuring care, but also represent powerful tools for improving care using decision support. Specific areas in which we have already seen significant benefit include reducing the unnecessary use of laboratory testing, reporting important abnormalities to key providers rapidly, prevention and detection of adverse drug events, initiatives to change prescribing patterns to reduce drug costs and making critical pathways available to providers. Our next major effort will be introduce computerized guidelines on a more widespread basis, which will be challenging. However, the advent of managed care in the US has produced strong incentives to provide high quality care at low cost and our perspective is that only with better IS than exist today will this be possible without compromising quality. Such systems make feasible implementation of quality measurement, care improvement and cost reduction initiatives on a scale which could not previously be considered.

A computer-based outpatient clinical referral system.

The process of generating a clinical referral for a patient, and the resulting transfer of information from the primary care physician to the specialist and back again, are key components in the struggle to deliver less costly and more effective clinical care. We have created a computer-based, outpatient clinical referral application that facilitates: (1) identifying an appropriate specialist; (2) collecting the clinical, demographic, and financial data required to generate a referral; and (3) transferring the information between the specialist and the primary care physician (PCP). This article describes the development of the application itself and several of the knowledge bases that were created to facilitate this process. Preliminary results indicate that the new computer-based referral process is faster to use than conventional methods.

Amphetamine poisoning in dogs.

Amphetamine intoxication in dogs referred to the Veterinary Diagnostic Laboratory or the Veterinary Hospital of the University of Minnesota was characterized by excitement, agitation, hyperthermia, and convulsive episodes that could be confused with other convulsant poisonings. Extraction procedures on stomach contents or urine enabled indentification of the drug, using ultraviolet spectrophotometry.

Developing interactive computer-based simulations: an object-oriented development methodology enhances computer-assisted instruction.

The purpose of this research was to investigate the application of object-oriented technology and AI techniques to enhance development of computer-based training simulations. Towards that end, a comprehensive computer-assisted instructional unit was developed to teach the skills and concepts of window-based applications, the OS/2 desktop, and the use of a patient care information system. By taking advantage of sophisticated computer graphics for the visual representation of objects and the behavioral modeling capabilities of the object-oriented language, domain knowledge modeling and human-computer interactions were implemented without complex natural language processing techniques. The results of this research indicate that nurses and physicians are able to learn the basic skills and concepts of computer systems and how to query for patient information. The new methodology described for building these computer-assisted instructional simulations significantly eased the training and teaching of large numbers of nurses and physicians and simplified their transition to a complex, computer-based hospital information system environment.

Physiologic trend detection and artifact rejection: a parallel implementation of a multi-state Kalman filtering algorithm.

Using a parallel implementation of the multi-state Kalman filtering algorithm, we have developed an accurate method of reliably detecting and identifying trends, abrupt changes, and artifacts from multiple physiologic data streams in real-time. The Kalman filter algorithm was implemented within an innovative software architecture for parallel computation: a parallel process trellis. Examples, processed in real-time, of both simulated and actual data serve to illustrate the potential value of the Kalman filter as a tool in physiologic monitoring.