A characterization of local LOINC mapping for laboratory tests in three large institutions.

OBJECTIVES: We characterized the use of laboratory LOINC® codes in three large institutions, focused on the following questions: 1) How many local codes had been voluntarily mapped to LOINC codes by each institution? 2) Could additional mappings be found by expert manual review for any local codes that were not initially mapped to LOINC codes by the local institution? and 3) Are there any common characteristics of unmapped local codes that might explain why some local codes were not mapped to LOINC codes by the local institution? METHODS: With Institutional Review Board (IRB) approval, we obtained deidentified data from three large institutions. We calculated the percentage of local codes that have been mapped to LOINC by personnel at each of the institutions. We also analyzed a sample of unmapped local codes to determine whether any additional LOINC mappings could be made and identify common characteristics that might explain why some local codes did not have mappings. RESULTS: Concept type coverage and concept token coverage (volume of instance data covered) of local codes mapped to LOINC codes were 0.44/0.59, 0.78/0.78 and 0.79/0.88 for ARUP, Intermountain, and Regenstrief, respectively. After additional expert manual mapping, the results showed mapping rates of 0.63/0.72, 0.83/0.80 and 0.88/0.90, respectively. After excluding local codes which were not useful for inter-institutional data exchange, the mapping rates became 0.73/0.79, 0.90/0.99 and 0.93/0.997, respectively. CONCLUSIONS: Local codes for two institutions could be mapped to LOINC codes with 99% or better concept token coverage, but mapping for a third institution (a reference laboratory) only achieved 79% concept token coverage. Our research supports the conclusions of others that not all local codes should be assigned LOINC codes. There should also be public discussions to develop more precise rules for when LOINC codes should be assigned.

Heat shock protein inhibitors increase the efficacy of measles virotherapy.

Oncolytic measles virus strains have activity against multiple tumor types and are currently in phase I clinical testing. Induction of the heat shock protein 70 (HSP70) constitutes one of the earliest changes in cellular gene expression following infection with RNA viruses including measles virus, and HSP70 upregulation induced by heat shock has been shown to result in increased measles virus cytotoxicity. HSP90 inhibitors such as geldanamycin (GA) or 17-allylaminogeldanamycin result in pharmacologic upregulation of HSP70 and they are currently in clinical testing as cancer therapeutics. We therefore investigated the hypothesis that heat shock protein inhibitors could augment the measles virus-induced cytopathic effect. We tested the combination of a measles virus derivative expressing soluble human carcinoembryonic antigen (MV-CEA) and GA in MDA-MB-231 (breast), SKOV3.IP (ovarian) and TE671 (rhabdomyosarcoma) cancer cell lines. Optimal synergy was accomplished when GA treatment was initiated 6-24 h following MV infection. Western immunoblotting confirmed HSP70 upregulation in combination-treated cells. Combination treatment resulted in statistically significant increase in syncytia formation as compared to MV-CEA infection alone. Clonogenic assays demonstrated significant decrease in tumor colony formation in MV-CEA/GA combination-treated cells. In addition there was increase in apoptosis by 4,6-diamidino-2-phenylindole staining. Western immunoblotting for caspase-9, caspase-8, caspase-3 and poly(ADP-ribose) polymerase (PARP) demonstrated increase in cleaved caspase-8 and PARP. The pan-caspase inhibitor Z-VAD-FMK and caspase-8 inhibitor Z-IETD-FMK, but not the caspase-9 inhibitor Z-IEHD-FMK, protected tumor cells from MV-CEA/GA-induced PARP activation, indicating that apoptosis in combination-treated cells occurs mainly via the extrinsic caspase pathway. Treatment of normal cells, such as normal human fibroblasts, however, with the MV-CEA/GA combination, did not result in cytopathic effect, indicating that GA did not alter the MV-CEA specificity for tumor cells. One-step viral growth curves, western immunoblotting for MV-N protein expression, QRT-PCR quantitation of MV-genome copy number and CEA levels showed comparable proliferation of MV-CEA in GA-treated vs -untreated tumor cells. Rho activation assays and western blot for total RhoA, a GTPase associated with the actin cytoskeleton, demonstrated decrease in RhoA activation in combination-treated cells, a change previously shown to be associated with increase in paramyxovirus-induced cell-cell fusion. The enhanced cytopathic effect resulting from measles virus/GA combination supports the translational potential of this approach in the treatment of cancer.

Rising incidence and persistently high mortality of hospitalized pneumonia: a 10-year population-based study in Denmark.

BACKGROUND: Little is known about temporal trends in the incidence and mortality of pneumonia in the general population. METHODS: We conducted a population-based cohort study in three Danish counties (population 1.4 million) to examine changes in the incidence and 30- and 90-day mortality associated with hospitalized pneumonia between 1994 and 2004. All adults hospitalized with a first-time diagnosis of pneumonia (n = 41 793) were identified in hospital discharge registries and followed for mortality through the Danish Civil Registry System. We determined age-standardized incidence rates and adjusted mortality rates associated with calendar year, gender, age and comorbidity. RESULTS: Between 1994 and 2003, the incidence of hospitalized pneumonia amongst adults increased from 288 per 100 000 person-years to 442 per 100 000 person-years, equivalent to an age-standardized incidence rate ratio of 1.50. The cumulative mortality within 30 and 90 days of admission was 15.2% and 21.9%, respectively, ranging from a 90-day mortality of 2.5% in patients aged 15-39 years to 34.7% in those aged 80 and over. Advanced age was the most important poor prognostic factor, followed by a high comorbidity score and male gender. The adjusted mortality rate ratios amongst patients with hospitalized pneumonia in 1999-2004, when compared with 1994-1998, were 0.89 (95% CI 0.85-0.94) after 30 days and 0.91 (95% CI 0.88-0.95) after 90 days. CONCLUSIONS: The incidence of hospitalized pneumonia in Denmark has increased considerably during the last 10 years and, combined with persistently high mortality rates, is of clinical and public health concern.

Pursuing integration of performance measures into electronic medical records: beta-adrenergic receptor antagonist medications.

OBJECTIVE: Electronic medical records seldom integrate performance indicators into daily operations. Assessing quality indicators traditionally requires resource intensive chart reviews of small samples. We sought to use an electronic medical record to assess use of beta-adrenergic antagonist medications (beta-blockers) following myocardial infarction, to compare a standardized manual assessment with assessment using electronic medical records, and to discuss potential for future integration of performance indicators into electronic records. DESIGN: Cross-sectional data analysis. SETTING: An urban academic medical center. PARTICIPANTS: US Medicare beneficiaries 65 years of age or older, admitted to hospital with myocardial infarction between 1995 and 1999. MEASUREMENTS AND MAIN RESULTS: Manual chart review was compared with a computer driven assessment of electronic records. Administration of beta-blockers and cases excluded from use of beta-blockers were measured, based on Medicare criteria. Among 4490 older adults, 391 (4%) of 9018 hospital admissions contained codes for myocardial infarction. In 323 (83%) of the 391 hospital admissions, criteria for excluding beta-blockers were met; 235 (60%) were excluded due to heart failure. Of 68 hospital admissions for myocardial infarction that did not meet exclusion criteria, physicians prescribed beta-blockers in 49 (72%) on admission and 42 (62%) at discharge. Compared with manual chart review, electronic review had a sensitivity of 83-100% and led to fewer false negative findings. CONCLUSIONS: An electronic medical records system can be used instead of chart review to measure use of beta-blockers after myocardial infarction. This should lead to integration of real time automated performance measurement into electronic medical records.

Conceptual alignment of electronic health record data with guideline and workflow knowledge.

Even though computerized practice guidelines and workflow management (WfM) are proven effective techniques to improving quality of care and reducing costs, they are not widely deployed today. One reason for this is the impedance mismatch between guideline systems and electronic health record (EHR) systems. This paper presents the Unified Service Action Model (USAM) that has been developed for the HL7 Reference Information Model (RIM) and that conceptually integrates guidelines and WfM in the EHR. We argue that the information items recorded in the EHR are logically similar to elements of guideline and WfM definitions. Therefore, the USAM suggests that guidelines and EHR reuse the same information structures. This reuse is possible through a technique borrowed from natural language grammar and modal logic. The conceptual alignment of guidelines, WfM and the EHR could facilitate the sharing and deployment of guidelines in routine health care.

Hickam 2000: the maturation of, and linkages between, medical informatics and bioinformatics.

I have always been infatuated with computers and convinced of their potential for solving problems in biologic research and clinical care. In the 1960s I thought we could use the computer to predict the shape of macromolecules from their chemical formulas and fundamental physical chemical principles. However, with the computers of the 1960s that was a fantasy. So I focused on the use of computers to manage medical record content and to assist with clinical care. The Electronic Medical Record (EMR) we began developing in 1972 with 33 diabetes patients now carries nearly 300 million separate results for more than 3 million patients. The data include lab and other diagnostic studies, dictated notes, orders, encounter records, radiology images, electrocardiograph tracings, and motion cardiac echoes, and the care provider at Indiana University and Wishard Hospital is accessed 10 million times per year. We have also agitated for standards to make the collection of these data easier. This work has become part of a field called medical informatics. In the meantime, the application of computers to biology has rapidly matured into a field called bioinformatics, and researchers in this field now provide annotated databases for many categories of molecules, programs for "matching" newly discovered genomic sequences with previously studied sequences, and systems for storing and processing massive amounts of genomic and molemic data. They have developed sophisticated methods for predicting the shape of biologic macromolecules and other important insights about biology and evolution. Medical informatics and bioinformatics intersect at many points. The most important intersection is between electronic medical records and the human specimen databases that can link genotype to the phenotype, as needed, to unravel polygenetic disease causality. The National Cancer Institute is embarking on an intriguing effort to use EMRs (phenotype) to link to paraffin blocks (genotype) in pathology laboratories where opportunities for cancer genomic discovery are open. We will participate in this effort and look forward to bending the EMR we developed for clinical use to bioinformatics uses as well.

A multicenter dose-escalation trial with denileukin diftitox (ONTAK, DAB(389)IL-2) in patients with severe psoriasis.

BACKGROUND: Denileukin diftitox, a fusion protein targeting both malignant and normal activated lymphocytes, has been shown previously to have antipsoriatic activity. However, the ideal dosing regimen for treating psoriasis was not established. OBJECTIVE: We examined the safety and efficacy of denileukin diftitox in patients with severe plaque-type psoriasis. METHODS: This was a cohort dose-escalation trial. Patients were administered denileukin diftitox on 3 consecutive days every other week. Patients were evaluated for toxicity, improvement in psoriasis, immunogenicity, and serum levels. RESULTS: Thirty-five patients were treated at 3 dose levels. Eight patients had a 50% decrease or more in Psoriasis Area and Severity Index score from baseline (0/10 at 0.5 microg/kg per day, 1/10 at 1.5 microg/kg per day, and 7/15 at 5 microg/kg per day). Adverse events primarily consisted of constitutional events and skin reactions. CONCLUSIONS: The potential antipsoriatic activity of denileukin diftitox demonstrated in this study was comparable to that observed in other psoriasis studies with this agent. However, this dosing regimen was better tolerated than the dosing regimen used in the last study with denileukin diftitox in psoriasis patients.

Electronic laboratory reporting: barriers, solutions and findings.

Electronic laboratory reporting can improve surveillance for notifiable conditions. Building on standards for message structure and content, we have implemented an electronic laboratory reporting system by building on the infrastructure created for the Indiana Network for Patient Care (INPC). The system has proven reliable in delivering results and scalable to multiple laboratories over 36 months of use. In April 2000, the system identified over 1,000 cases of notifiable conditions from the laboratories at four different laboratories. Our experience in developing the system has highlighted the need for improved compliance with HL7 result message formats by the laboratory information systems and more structured reporting of results for tests such as microbiology including consistent use of the abnormal flag.

A computerized reminder system to increase the use of preventive care for hospitalized patients.

BACKGROUND: Although they are effective in outpatient settings, computerized reminders have not been proved to increase preventive care in inpatient settings. METHODS: We conducted a randomized, controlled trial to determine the effects of computerized reminders on the rates at which four preventive therapies were ordered for inpatients. During an 18-month study period, a computerized system processed on-line information for all 6371 patients admitted to a general-medicine service (for a total of 10,065 hospitalizations), generating preventive care reminders as appropriate. Physicians who were in the intervention group viewed these reminders when they were using a computerized order-entry system for inpatients. RESULTS: The reminder system identified 3416 patients (53.6 percent) as eligible for preventive measures that had not been ordered by the admitting physician. For patients with at least one indication, computerized reminders resulted in higher adjusted ordering rates for pneumococcal vaccination (35.8 percent of the patients in the intervention group vs. 0.8 percent of those in the control group, P<0.001), influenza vaccination (51.4 percent vs. 1.0 percent, P< 0.001), prophylactic heparin (32.2 percent vs. 18.9 percent, P<0.001), and prophylactic aspirin at discharge (36.4 percent vs. 27.6 percent, P<0.001). CONCLUSIONS: A majority of hospitalized patients in this study were eligible for preventive measures, and computerized reminders significantly increased the rate of delivery of such therapies.

A randomized, double-blind comparison of the efficacy and tolerability of once-daily modified-release diltiazem capsules with once-daily amlodipine tablets in patients with stable angina.

A randomized, double-blind, parallel-group study comparing the efficacy and tolerability of once-daily diltiazem capsules with amlodipine tablets in patients with stable angina. After a run-in period of 1 to 3 weeks, 34 patients received once-daily diltiazem and 33 patients received amlodipine. Patients received either diltiazem, 240 mg/day, or amlodipine, 5 mg/day, for 2 weeks followed by diltiazem, 360 mg/day, or amlodipine, 10 mg/day, for 2 weeks. Standard treadmill exercise testing was the primary efficacy assessment. Patients also recorded incidence of angina attacks and use of glyceryl trinitrate spray. Both treatments gave significant improvement in time to onset of angina and time to maximal exercise. With the exception of amlodipine, 5 mg/day, both treatments gave significant increases in time to 1-mm ST segment depression. Diltiazem, 360 mg/day, gave a significant decrease in rate pressure product. There were no significant treatment differences in any of the exercise test parameters. Both treatments reduced incidence of angina attacks and use of glyceryl trinitrate spray. The incidence of edema was significantly less in patients receiving diltiazem. In conclusion, both treatments were effective in controlling patients' angina, but diltiazem was better tolerated, with a lower incidence of edema.

Controlled trial of direct physician order entry: effects on physicians' time utilization in ambulatory primary care internal medicine practices.

OBJECTIVE: Direct physician order entry (POE) offers many potential benefits, but evidence suggests that POE requires substantially more time than traditional paper-based ordering methods. The Medical Gopher is a well-accepted system for direct POE that has been in use for more than 15 years. The authors hypothesized that physicians using the Gopher would not spend any more time writing orders than physicians using paper-based methods. DESIGN: A randomized controlled trial of POE using the Medical Gopher system in 11 primary care internal medicine practices. MEASUREMENTS: The authors collected detailed time use data using time motion studies of the physicians and surveyed their opinions about the POE system. RESULTS: The authors found that physicians using the Gopher spent 2.2 min more per patient overall, but when duplicative and administrative tasks were taken into account, physicians were found to have spent only 0.43 min more per patient. With experience, the order entry time fell by 3.73 min per patient. The survey revealed that the physicians believed that the system improved their patient care and wanted the Gopher to continue to be available in their practices. CONCLUSIONS: Little extra time, if any, was required for physicians to use the POE system. With experience in its use, physicians may even save time while enjoying the many benefits of POE.

Bedside vital signs capture for the non-ICU setting--an open source, PC-based solution.

The efficient and reliable capture of vital signs and other bedside data in the non-ICU setting has been a challenging problem for the medical informatics community. The problem is compounded by the complexities associated with storage of this data into an electronic medical record system (EMRS). There are a lack of off-the-shelf solutions that satisfy the basic system requirements of bedside data capture, user authentication, data validation prior to storage, error handling, and convenience. With the current state of technology available, we feel the solution to this problem requires the presence of a PC with custom interface software at the bedside. This allows for the successful interface between available vital signs capture devices, existing EMRS s, and the user. This report summarizes the alternatives we found and our proposed solution to this important problem.

Integration of radiographic images with an electronic medical record.

Radiographic images are important and expensive diagnostic tests. However, the provider caring for the patient often does not review the images directly due to time constraints. Institutions can use picture archiving and communications systems to make images more available to the provider, but this may not be the best solution. We integrated radiographic image review into the Regenstrief Medical Record System in order to address this problem. To achieve adequate performance, we store JPEG compressed images directly in the RMRS. Currently, physicians review about 5% of all radiographic studies using the RMRS image review function.

Representing and querying conceptual graphs with relational database management systems is possible.

This is an experimental study on the feasibility of maintaining medical concept dictionaries in production grade relational database management systems (RDBMS.) In the past, RDBMS did not support transitive relational structures and had therefore been unsuitable for managing knowledge bases. The revised SQL-99 standard, however, may change this. In this paper we show that modern RDBMS that support recursive queries are capable of querying transitive relationships in a generic data model. We show a simple but efficient indexed representation of transitive closure. We could confirm that even challenging combined transitive relationships can be queried in SQL.

A comparison of a printed patient summary document with its electronic equivalent: early results.

Clinicians are always searching for efficient access to clinical data. The Regenstrief Medical Record System has a printed report that fills this niche: Pocket Rounds. Handheld computers may offer an alternative, but it is unclear how effectively a handheld computer can display such data. We surveyed residents and students on the general medicine services for their opinions regarding Pocket Rounds. Those with handheld computers were given access to an electronic version of Pocket Rounds-e-Rounds. We surveyed the subjects who used e-Rounds for their opinions on the electronic format and how it compared to paper. Users overall satisfaction with Pocket Rounds was 5.8 on a seven-point scale. User s overall satisfaction for e-Rounds was 5.6 on a seven-point scale. The most useful function was retrieval of lab data for both modalities. The results suggest that the electronic format is a viable alternative to paper. Further evaluation is needed, and we plan a prospective controlled trial to study this further.

Secure Internet video conferencing for assessing acute medical problems in a nursing facility.

Although video-based teleconferencing is becoming more widespread in the medical profession, especially for scheduled consultations, applications for rapid assessment of acute medical problems are rare. Use of such a video system in a nursing facility may be especially beneficial, because physicians are often not immediately available to evaluate patients. We have assembled and tested a portable, wireless conferencing system to prepare for a randomized trial of the system s influence on resource utilization and satisfaction. The system includes a rolling cart with video conferencing hardware and software, a remotely controllable digital camera, light, wireless network, and battery. A semi-automated paging system informs physicians of patient s study status and indications for conferencing. Data transmission occurs wirelessly in the nursing home and then through Internet cables to the physician s home. This provides sufficient bandwidth to support quality motion images. IPsec secures communications. Despite human and technical challenges, this system is affordable and functional.

Integrating medical information and knowledge in the HL7 RIM.

Guidelines have a proven ability to improve quality of health care and reduce cost, yet, guidelines are not very well deployed at the point of care. This is largely due to the impedance mismatch between decision support modules and the Electronic Medical Record (EMR.) The Unified Service Action Model (USAM) as part of the HL7's Reference Information Model provides a conceptual integration between patient data and medical knowledge. The USAM defines one action-oriented information structure for patient data, concept definitions, action plans, conditionals, and goals. This suggests a new approach to the problem of sharing data and knowledge, effectively working around the problem of missing domain terminology.