H.H.M. Korsten

METHODOLOGICAL REVIEW: Approaches for creating computer-interpretable guidelines that facilitate decision support

During the last decade, studies have shown the benefits of using clinical guidelines in the practice of medicine. Although the importance of these guidelines is widely recognized, health care organizations typically pay more attention to guideline development than to guideline implementation for routine use in daily care. However, studies have shown that clinicians are often not familiar with written guidelines and do not apply them appropriately during the actual care process. Implementing guidelines in computer-based decision support systems promises to improve the acceptance and application of guidelines in daily practice because the actions and observations of health care workers are monitored and advice is generated whenever a guideline is not followed. Such implementations are increasingly applied in diverse areas such as policy development, utilization management, education, clinical trials, and workflow facilitation. Many parties are developing computer-based guidelines as well as decision support systems that incorporate these guidelines. This paper reviews generic approaches for developing and implementing computer-based guidelines that facilitate decision support. It addresses guideline representation, acquisition, verification and execution aspects. The paper describes five approaches (the Arden Syntax, GuideLine Interchange Format (GLIF), PROforma, Asbru and EON), after the approaches are compared and discussed.

Design and implementation of a framework to support the development of clinical guidelines

This paper describes and discusses a framework that facilitates the development of clinical guideline application tasks. The framework, named GASTON covers all stages in the guideline development process, ranging from the definition of models that represent guidelines to the implementation of run-time systems that provide decision support, based on the guidelines that were developed during the earlier stages. The GASTON framework consists of (1) a newly developed guideline representation formalism that uses the concepts of primitives, problem-solving methods (PSMs) and ontologies to represent the guidelines of various complexity and granularity and different application domains, (2) a guideline authoring environment that enables guideline authors to define the guidelines, based on the newly developed guideline representation formalism and (3) a guideline execution environment that translates defined guidelines into a more efficient symbol level representation, which can be read in and processed by an execution time engine. The paper describes a number of design criteria that were formulated regarding the aspects of guideline representation, guideline authoring and guideline execution and explains the framework by example in terms of the four stages that were identified in the guideline development process and the tools that were developed to support each stage. It also shows examples of systems that were developed by means of the GASTON framework.

Long-lasting Epidural Sensory Blockade by n-Butyl-p-Aminobenzoate in the Terminally Ill Intractable Cancer Pain Patient

An aqueous suspension of n-butyl-p-aminobenzoate (BAB), a highly lipid-soluble congener of benzocaine, was applied epidurally in terminally ill cancer patients with intractable pain. The suspension consisted of 10% BAB and 0.025% of the nonionic surfactant polysorbate 80 in 0.9% sodium chloride. Twelve consecutive patients received epidural BAB because pain was uncontrollable either by palliative radiotherapy or oral or epidural administrations of analgesics. The catheter or injecting needle was positioned at the segmental level of the pain. Repeated epidural injections were administered. In all patients, long-lasting sensory blockade (segmental analgesia) occurred, accompanied by a marked reduction or even absence of pain. In all patients, treatment with epidural opioids, alone or combined with local anesthetics, was no longer necessary. Five of the 12 patients did not require further administration of oral opioids. Motor, bowel, and bladder function were well preserved. In 6 patients, extensive necropsy of the spinal cord and spinal nerves did not reveal pathomorphologic changes. The outer aspect of the dura showed signs of focal necrosis on microscopy, yet its collagen structure and thickness were unchanged. Epidurally, focal infiltrative reactions were seen. The epidural use of an extremely lipid-soluble--hence hydrophobic--local anesthetic, with an exceptionally low pKa (2.3), formulated in suspension of the base, is conceptually innovative and needs further investigation. The authors conclude that the epidural administration of a BAB suspension may be an effective alternative to the neurolytic agents alcohol and phenol and may replace procedures such as cordotomy. Further investigation to determine the safety of BAB in this patient group appears warranted.

GASTON: an architecture for the acquisition and execution of clinical guideline-application tasks

Recently, studies have shown the benefits of using clinical guidelines in the practice of medicine. There have been numerous efforts to develop clinical decision support systems that support guideline-based care in an automated fashion, covering a wide range of clinical settings and tasks. Despite these efforts, only a few systems progressed beyond the prototype stage and the research laboratory. For guideline-based clinical decision support systems to be successful, a balance must be made between intuitive but imprecise representations usually encountered by most of todays systems and representations that support a strong underlying clinical performance model. The project described in this paper tries to achieve such a balance. It presents the GASTON architecture that contains a set of reusable software components for the application of guidelines, including design-time components to facilitate the guideline authoring process based on guideline representation models along with execution-time components for building decision support systems that incorporate these guidelines. This architecture was used to develop several guideline representation models such as a rule-based representation to model rule-based guidelines and guideline representation models that address more complex tasks. Also, decision support systems that incorporate these models were developed with the architecture. For the representation and application of various classes of guidelines, rules were also viewed as instances of more complex tasks. By identifying similar characteristics of sets of rules, we developed several tasks such as a drug interaction and drug contraindication task. Based on these models, we have developed and validated guidelines and decision support systems for use in several application domains such as intensive care, family physicians and psychiatry. In order to be able to represent more complex time-oriented plans, new guideline representation models are being developed.Recently, studies have shown the benefits of using clinical guidelines in the practice of medicine. There have been numerous efforts to develop clinical decision support systems that support guideline-based care in an automated fashion, covering a wide range of clinical settings and tasks. Despite these efforts, only a few systems progressed beyond the prototype stage and the research laboratory. For guideline-based clinical decision support systems to be successful, a balance must be made between intuitive but imprecise representations usually encountered by most of todays systems and representations that support a strong underlying clinical performance model. The project described in this paper tries to achieve such a balance. It presents the GASTON architecture that contains a set of reusable software components for the application of guidelines, including design-time components to facilitate the guideline authoring process based on guideline representation models along with execution-time components for building decision support systems that incorporate these guidelines. This architecture was used to develop several guideline representation models such as a rule-based representation to model rule-based guidelines and guideline representation models that address more complex tasks. Also, decision support systems that incorporate these models were developed with the architecture. For the representation and application of various classes of guidelines, rules were also viewed as instances of more complex tasks. By identifying similar characteristics of sets of rules, we developed several tasks such as a drug intera ction and drug contraindication task. Based on these models, we have developed and validated guidelines and decision support systems for use in several application domains such as intensive care, family physicians and psychiatry. In order to be able to represent more complex time-oriented plans, new guideline representation models are being developed.

Information processing during cardiac surgery: an event related potential study

The aim of this study was to investigate whether information processing persists during general anesthesia, and if so, to determine the relationship between the degree of cognitive processing measured during anesthesia and the presence or absence of intraoperative memories measured after anesthesia. Subjects were 12 patients, undergoing cardiac surgery with propofol/alfentanil anesthesia. During several periods of the operation, event related potentials (ERPs) to frequent and infrequent tones of different pitch were analyzed. After the operation, a word recognition task with ERP recording was administered to determine whether intraoperatively presented words would elicit a (covert) recognition reaction in the brain. ERP wave forms could be obtained during the intraoperative recording periods but differed substantially from those in the awake state. The presence of ERP components up to 500 msec after stimulus presentation suggests that auditory information processing continued during anesthesia up to a certain level of cognition. Intraoperative ERPs to frequent and infrequent tones were not different from each other implying that differences in pitch could not be detected. The postoperative results demonstrated evidence for intraoperative memories in 3 patients. For 2 of these 3 patients, low propofol levels as well as reliable ERPs with large amplitudes were found close to the moment of information presentation. The results emphasize the importance of combining intra- and postoperative measurements and suggest that late ERP components might be used as indicators of an increased risk of auditory perception.

Cardiac image segmentation for contrast agent videodensitometry

Indicator dilution techniques are widely used in the intensive care unit and operating room for cardiac parameter measurements. However, the invasiveness of current techniques represents a limitation for their clinical use. The development of stable ultrasound contrast agents allows new applications of the indicator dilution method. Ultrasound contrast agent dilutions permit an echographic noninvasive measurement of cardiac output, ejection fraction, and blood volumes. The indicator dilution curves are measured by videodensitometry of specific regions of interest and processed for the cardiac parameter assessment. Therefore, the major indicator dilution imaging issue is the detection of proper contrast videodensitometry regions that maximize the signal-to-noise ratio of the measured indicator dilution curves. This work presents an automatic contour detection algorithm for indicator dilution videodensitometry. The algorithm consists of a radial filter combined with an outlier correction. It maximizes the region of interest by excluding cardiac structures that act as interference to the videodensitometric analysis. It is fast, projection independent, and allows the simultaneous detection of multiple contours in real time. The system is compared to manual contour definition on both echographic and magnetic resonance images.

The application of ontologies and problem-solving methods for the development of shareable guidelines

Recently, studies have shown the benefits of using clinical guidelines in the practice of medicine. Computer-based clinical guidelines are increasingly applied in diverse areas such as policy development, utilization management, education, conduct of clinical trials, and workflow facilitation. This paper discusses some of the representations suggested in literature, discusses their weak and strong points, and demonstrates and discusses a new approach that extends earlier developed formalisms by combining primitives, ontologies and the use of problem-solving methods (PSMs). The approach is supported by a framework that facilitates the entire guideline authoring process. The paper demonstrates this framework and presents examples of guidelines, PSMs and systems that were developed by means of this approach. The overall goal of this approach is to improve the acceptance of shareable guidelines and decision support systems in daily care by facilitating the guideline acquisition and execution phases.

Epidural and intrathecal n-butyl-p-aminobenzoate solution in the rat : Comparison with bupivacaine

Background Epidural administration of an aqueous suspension of n‐butyl‐p‐aminobenzoate (BAB) to humans results in long‐lasting sensory blockade without motor block. The dose‐response of BAB administered epidurally and intrathecally as a solution was studied in rats to define the local anesthetic properties in an established animal model. Methods The time course of changes in tail withdrawal latency and motor function were determined in rats after epidural or intrathecal administration of solutions of BAB or bupivacaine. The dose‐response relation was determined and median effective dose values were calculated. Results After epidural and intrathecal administration of BAB solutions, the onset and duration of the antinociceptive action were comparable to bupivacaine. Median effective dose values for tail‐withdrawal latency of 6 s or more were significantly greater for BAB. After both routes of administration, BAB clearly affected motor function. Conclusions When administered epidurally and intrathecally as a solution, BAB is a local anesthetic of relative low potency with onset and duration of action comparable to those of bupivacaine. These findings suggest that the long‐lasting action obtained after applying BAB suspension results from the slow dissolution (continuous release) of the solid BAB deposited in the epidural space.

Identification of ultrasound contrast agent dilution systems for ejection fraction measurements

Left ventricular ejection fraction is an important cardiac-efficiency measure. Standard estimations are based on geometric analysis and modeling; they require time and experienced cardiologists. Alternative methods make use of indicator dilutions, but they are invasive due to the need for catheterization. This study presents a new minimally invasive indicator dilution technique for ejection fraction quantification. It is based on a peripheral injection of an ultrasound contrast agent bolus. Left atrium and left ventricle acoustic intensities are recorded versus time by transthoracic echocardiography. The measured curves are corrected for attenuation distortion and processed by an adaptive Wiener deconvolution algorithm for the estimation of the left ventricle impulse response, which is interpolated by a monocompartment exponential model for the ejection fraction assessment. This technique measures forward ejection fraction, which excludes regurgitant volumes. The feasibility of the method was tested on a group of 20 patients with left ventricular ejection fractions going from 10% to 70%. The results are promising and show a 0.93 correlation coefficient with echographic bi-plane ejection fraction measurements. A more extensive validation as well as an investigation on the method applicability for valve insufficiency and right ventricular ejection fraction quantification will be an object of future study.

Long-lasting Epidural Sensory Blockade by n-Butyl p-Aminobenzoate in the Dog: Neurotoxic or Local Anesthetic Effect?

An aqueous suspension of n-butyl p-aminobenzoate (BAB), a highly lipid-soluble congener of benzocaine, was applied epidurally and around ulnar nerves in dogs. The suspension consisted of 10% BAB and 0.025% polysorbate in 0.9% NaCl. Sensory effects were tested by electrical stimulation. Three epidural injections were given, and the dogs were killed after 21 days. The increase in stimulation threshold was comparable to the effect of lidocaine in a concentration between 0.5% and 1%. Increased sensory threshold lasted for days, whereas no long-lasting motor effects were observed. Pathomorphologic changes were found primarily in the dorsal spinal nerve roots, although slight changes were also found in the ventral spinal roots. White matter degeneration was found only in the lumbar dorsal columns. This result suggested Wallerian degeneration in the dorsal spinal nerves and was at variance with recently published data on epidural BAB. No changes were observed in the ulnar nerves. The authors demonstrated that the pathomorphologic changes were induced by the BAB suspension and not by the suspending additive polysorbate 80. It was postulated that the suspension of BAB, which contains particles of a median size of 15 microns, was mainly confined to the dorsal epidural space where neurolytic changes in axons of the dorsal spinal nerve roots and dorsal columns are induced. This may explain the long-lasting sensory effects seen in intractable cancer pain patients after epidural BAB administration. More research is necessary to define the distribution of BAB in nervous tissue after its epidural administration and to better characterize toxicity, neurolytic effects, and regeneration of nervous tissue after BAB administrations.