A frame-based representation for a bedside ventilator weaning protocol.

We describe the use of a frame-based knowledge representation to construct an adequately-explicit bedside clinical decision support application for ventilator weaning. The application consists of a data entry form, a knowledge base, an inference engine, and a patient database. The knowledge base contains database queries, a data dictionary, and decision frames. A frame consists of a title, a list of findings necessary to make a decision or carry out an action, and a logic or mathematical statement to determine its output. Frames for knowledge representation are advantageous because they can be created, visualized, and conceptualized as self-contained entities that correspond to accepted medical constructs. They facilitate knowledge engineering and provide understandable explanations of protocol outputs for clinicians. Our frames are elements of a hierarchical decision process. In addition to running diagnostic and therapeutic logic, frames can run database queries, make changes to the user interface, and modify computer variables.

Support for basic gerontological research in the USA.

Support for research in basic gerontology in the United States of America is briefly described. The support mechanisms, how to apply for a grant, and priority areas of research are outlined, and recent progress in a few of these priority areas is discussed. In general, government support for biogerontology research has been generous, and as a result considerable progress has been made in understanding the molecular mechanisms of aging in animal model systems. Translation of these findings to humans, and development of interventions to promote healthy aging in humans remain an unfulfilled priority, but new knowledge and development of better technologies and model systems suggest an optimistic future.

The case for supporting basic research in gerontology.

Basic research on aging has moved well beyond describing the aging of physiological systems and developing theories of aging, to the pursuit of mechanistic answers to questions such as: Why do we age? Why do individuals within a population age differently? Why do different species have such different life spans? How do aging changes increase the risk of developing age-related disease? and Can we develop safe and effective interventions to reduce age-related disability? Two general areas of research promise to provide answers to these questions. One is the attempt to understand the mechanisms by which caloric restriction extends longevity and delays the onset of age-related disease. The other is the identification of genes which strongly influence the rate of aging in various animal model systems. Recent results in the latter area of research are providing new insights into the answers to these central aging questions and may help us understand how caloric restriction retards aging.

Program for testing biological interventions to promote healthy aging.

The National Institute on Aging (NIA) sponsored a workshop on September, 1999 to discuss the feasibility of establishing a program to evaluate potential intervention strategies to decelerate the rate of aging in mammals. The ultimate goal is to identify promising interventions in animals that might lead to clinical trials in humans. The participants discussed various animal models, biological endpoints and possible structure of such a program. The ability to implement such a program will require a decision by NIA staff about whether the anticipated benefits to be derived from identification of effective interventions under well controlled conditions in an animal model, in this case the mouse, would justify the anticipated cost of the testing program.

The HELP hospital information system: update 1998.

The HELP hospital information system has been operational at LDS Hospital since 1967. The system initially supported a heart catheterization laboratory and a post open heart Intensive Care Unit. Since the initial installation the system has been expanded to become an integrated hospital information system providing services with sophisticated clinical decision-support capabilities to a wide variety of clinical areas such as laboratory, nurse charting, radiology, pharmacy, etc. The HELP system is currently operational in multiple hospitals of LDS Hospital's parent health care enterprise--Intermountain Health Care (IHC). The HELP system has also been integrated into the daily operations of several other hospitals in addition to those at IHC. Evaluations of the system have shown: (1) it to be widely accepted by clinical staff; (2) computerized clinical decision-support is feasible; (3) the system provides improvements in patient care; and (4) the system has aided in providing more cost-effective patient care. Plans for making the transition from the 'function rich' HELP system to more modern hardware and software platforms are also discussed.

Apoptosis: a two-edged sword in aging.

Here we summarize briefly what is known about both the positive and negative impacts of apoptosis during aging in mammalian systems and also update an earlier review. It is important to understand both of these impacts to devise useful interventions. Such interventions include both physiological and molecular approaches, including transgenic interventions. The critical roles of the mitochondria in both generating reactive oxygen species, and in initiating apoptosis are recognized, suggesting that maintaining mitochondrial function could be an important therapeutic goal, especially in post-mitotic tissues. In contrast, the ability to eliminate unwanted, damaged and dysfunctional cells through apoptosis has anti-aging implications in mitotic tissues.

Apoptosis: a two-edged sword in aging.

It is now recognized that apoptosis plays an important role in many physiological processes, including aging and age-related diseases. Apoptosis plays both positive and negative roles in aging, and some of these roles are reviewed here. Of particular importance are the roles of apoptosis in reducing cancer incidence, and in promoting neurodegenerative disease. Therefore, the regulation of apoptosis is an inviting target for therapeutic interventions in aging and age-related disease.

Clinical event management using push technology--implementation and evaluation at two health care centers.

For two years, beginning in 1995, we developed and implemented a novel method for delivering patient information directly to clinicians. Using rules based logic to scan data bound for an electronic medical record, messages were automatically written that alert care providers to important patient information. These messages were transmitted electronically to either existing email accounts or to wide-screen pagers, or to both. This system now is operational at two medical centers. We describe the model and methods that led to its successful implementation and compare it to other ways of delivering patient information.

What does cell death have to do with aging?

When Lockshin and Zakeri discussed the relevance of apoptosis to aging 7 years ago, the common view was that apoptosis would have primarily a negative impact on aging by destroying essential and often irreplaceable cells. That view has now changed to one that acknowledges that there are two general ways in which apoptosis can play a role in aging: (1) elimination of damaged and presumably dysfunctional cells (e.g., fibroblasts, hepatocytes), which can then be replaced by cell proliferation, thereby maintaining homeostasis, and (2) elimination of essential post-mitotic cells (e.g., neurons, cardiac myocytes), which cannot be replaced, thereby leading to pathology. Evidence exists in two systems (fibroblasts and thymocytes/lymphocytes) that there are age-related decreases in the potential for apoptosis, although the molecular bases for the decreases in these two systems appear to differ. Upon becoming senescent, fibroblasts lose the ability to down-regulate expression of the bcl-2 gene in response to an apoptotic signal; thus, apoptosis is blocked even though an initiating signal has been received. In contrast, thymocytes/lymphocytes lack the ability to initiate the signal because of down-regulation of the cell surface receptor Fas. There is limited information available for other tissue types, and nothing is known about why and how age-related changes occur. An interesting observation is that the frequency of up-regulation of the bcl-2 gene as a result of chromosome translocation in otherwise normal B cells increases with age; the functional consequences of this phenomenon during aging are not known. The role of apoptosis in regulating cell number is also a promising area of research. The studies on liver damage and neoplastic lesions suggest an extremely important role for apoptosis in controlling cancer. This may be particularly important in the prostate where hypertrophy and/or cancer are a virtual certainty with ever-increasing age. It is not known whether the ability to undergo apoptosis declines in the prostate with increasing age, but it appears possible that it may, thus explaining the loss of control over cell number in this tissue. A particularly important area of research is whether apoptosis plays a role in the changing balance between bone formation and resorption observed during osteoporosis. Monica Driscoll has already pointed out that, "regulation and execution of cell death is an absolutely critical process that interfaces with nearly every aspect of life. Future investigation of the links of cell death to cellular aging and the aging of organisms should be an exciting enterprise." The results currently available do suggest that apoptosis is a process that may be important in aging, at least in some tissues, and the mechanism of its regulation, in particular, needs to be understood. Several tumor suppressor gene and oncogene products are involved in signal transduction associated with apoptosis, but it remains to be shown which of these, if any, are actually involved in "on-off" switches for apoptosis. Where great progress has been made is in understanding the events occurring after binding of either Fas ligand or tumor necrosis factor to their respective receptors. However, one area about which little is known is the identity of the signals that initiate this process in response to intracellular damage. Through continuing research on cell death mechanisms, funded by the NIA, we hope to provide answers to such fundamental questions as: 1. Are there age-related changes in apoptosis, and what role, if any, do these have in the aging process? 2. If age-related changes in apoptosis do occur, what molecular mechanisms are altered to produce these changes? 3. Can approaches be developed to improve the detection and elimination of damaged cells in vivo in tissues where cell replacement is possible? 4. Can death of damaged cells be attenuated or delayed in nonrenewable tissues, and, if so, is it advantageous to the org

Subtotal hysterectomy in modern gynecology: a decision analysis.

OBJECTIVE: Our purpose was to compare the risks and benefits of subtotal (supracervical) hysterectomy with those of total hysterectomy in women at low risk for cervical cancer. STUDY DESIGN: A decision analysis was performed. Baseline probabilities for operative and postoperative morbidity, mortality, and long-term quality of life were established for subtotal and total hysterectomy. RESULTS: Operative complication rates and ranges for total abdominal hysterectomy were infection 3.0% (3.0% to 20.0%), hemorrhage 2.0% (2.0% to 15.4%), and adjacent organ injury 1.0% (0.7% to 2.0%). Those for subtotal hysterectomy were infection 1.4% (1.0% to 5.0%), hemorrhage 2.0% (0.7% to 4.0%), and adjacent organ injury 0.7% (0.6% to 1.0%). Operative mortality, the risk for development of cervicovaginal cancer, and long-term adverse effects on sexual or vesicourethral function were low in both groups. CONCLUSIONS: Recently proposed benefits from subtotal hysterectomy are not well proven. Total hysterectomy remains the procedure of choice for most women.

Aging and regulation of apoptosis.

When Lockshin and Zakeri discussed the relevance of apoptosis to aging, the common view was that apoptosis had primarily a negative impact on aging by destroying essential and often irreplaceable cells. That view has now changed to one that acknowledges that there are two general ways in which apoptosis can play a role in aging: (1) elimination of damaged and presumably dysfunctional cells (e.g., fibroblasts, hepatocytes) which can then be replaced by cell proliferation, thereby maintaining homeostasis and elimination of essential postmitotic cells (e.g., neurons) which cannot be replaced, thereby leading to pathology. Evidence exists in two systems (fibroblasts and thymocytes/lymphocytes) that there are age-related decreases in the potential for apoptosis, although the molecular bases for these decreases appear to differ (Table II). Fibroblasts (and neurons?) lose the ability to downregulate bcl-2 in response to an apoptotic signal; thus, apoptosis is blocked even though an initiating signal has been received. In contrast, thymocytes/lymphocytes lack the ability to initiate the signal due to downregulation of the cell surface receptor Fas. There is limited information available for other tissue types, and nothing is known about why and how these age-related changes occur. An interesting observation, but not necessarily a critical one, is that the frequency of upregulation of the bcl-2 gene due to chromosome translocation increases with age. The role of apoptosis in regulating cell number is also a promising area of research. The studies on liver damage and neoplastic lesions suggest an extremely important role for apoptosis in controlling cancer. This may be particularly important in the prostate, where hypertrophy and cancer are a virtual certainty with ever-increasing age. It is not known whether the ability to undergo apoptosis declines in the prostate with increasing age, but it appears likely that it does. One problem in answering questions about the actual regulation of apoptosis is the lack of a quantitative assay. Apoptosis appears to be either "on" or "off" in cells, while the basic cell-killing machinery may often be present, but in an inactive form. Most assays for apoptosis are microscopic rather than kinetic, and the rate-limiting step may be at the level of the initiating signal. Thus, if CR, which extends the life span of rodents, does upregulate apoptosis, it is not clear how to quantify the magnitude of this effect or what should be quantified. The best one can do is to measure the frequency of occurrence of apoptotic bodies. This is essentially a pool size assay which provides little knowledge about how rapidly cells are leaving and entering the pool. Nevertheless, the results currently available do suggest that apoptosis is a process which may be important in aging, at least in some tissues, and the mechanism of its regulation needs to be understood. Although a variety of tumor suppressor gene and oncogene products are known to be involved in signal transduction associated with apoptosis, it remains to be shown which of these, if any, are actually involved in "on-off" switches for apoptosis and which might regulate the intrinsic rate of apoptosis. As Driscoll has already pointed out: "regulation and execution of cell death is an absolutely critical process that interfaces with nearly every aspect of life. Future investigation of the links of cell death to cellular aging and the aging of organisms should be an exciting enterprise."

Capturing clinical reports in a large academic medical center: feeding a central patient data repository.

Clinical reports, notes, and other narratives are highly used components in the patient record. Unfortunately, the methods by which these reports are generated are as diverse as the fiscal autonomy of academic clinical departments in a university-based health science center. In this paper, we report on electronically capturing clinical reports, notes, and other text fragments from several hospital sources and many outpatient clinics. The purpose of the capture is to feed the ACIS (Advanced Clinical Information System) central patient data repository that is in use at the University of Utah Health Sciences Center (UUHSC). A survey conducted in early 1994 indicated that about 917,150 reports were generated per year at UUHSC representing about 1.2 million pieces of paper, occupying about 2.3 gigabytes of storage. The most crucial problem encountered in capturing the reports was linking them to the proper patient. Systems that had functioning and well-maintained admit-discharge-transfer (ADT) information performed well, but systems that relied on the human dictator to identify patients, produced patient linkage errors. In our open loop telephone dictation systems this error rate averaged between 6 and 10%. Subsequent to the wide-spread availability of clinical reports on ACIS, this error rate dropped to 3-5%, presumably due to increased demand for on-line availability of this information. From clinical secretaries who use their word processor to create the clinical reports, the linkage error rate was < 1% due to the use of our Advanced Text Upload (ATU) utility. The clinical text component in ACIS contributed significantly to the success of a JCAHO site visit in December 1995.

Quality assessment and patient participation in care by means of a touch-screen computer.

Hospital characteristics vary greatly across a geographic area such as a state. Hospital peer groups internally exhibit similar characteristics and can be used as a basis for the analysis of data, the dissemination of information, and the adoption of continuous quality improvement project results. This paper reflects the efforts made toward the identification of hospital peer groups within the state of Michigan. Hospital characteristics data for fiscal year 1992 were obtained from the American Hospital Association's Annual Survey of Hospitals and the Health Care Financing Administration's MEDPRO database. Thirteen peer group clusters have been identified, reviewed, and commented on by the state's hospital association and have met general approval by hospital administrators across the state. The established peer groups are being used to identify the differences in patterns of care among hospitals in the state. The peer groups also are being used for the feedback of comparable data and the identification of hospitals for participation in continuous quality improvement projects. The next research objective is to experiment with other clustering techniques and other inpatient populations. The consistency of the peer groupings across all clustering techniques and across both Medicare and total inpatient populations will be studied.

An event model of medical information representation.

OBJECTIVE: Develop a model for structured and encoded representation of medical information that supports human review, decision support applications, ad hoc queries, statistical analysis, and natural-language processing. DESIGN: A medical information representation model was developed from manual and semiautomated analysis of patient data. The key assumption of the model is that medical information can be represented as a series of linked events. The event representation has two main components. The first component is a frame or template definition that specifies the attributes of the event. The second component is a structured vocabulary, the terms of which are taken as the values of the slots in the event template structure. Individual event instances are linked by specific named relationships. RESULTS: The proposed model was used to represent a chest-radiograph report. CONCLUSIONS: The event model of medical information representation provides a mechanism for formal definition of the logical structure of medical data and allows explicit time-oriented and associative relationships between event instances.