Mauro Torchio

A modular approach for representing and executing clinical guidelines

In this paper, we propose an approach for managing clinical guidelines. We outline a modular architecture, allowing us to separate two conceptually distinct aspects: the representation (and acquisition) of clinical guidelines and their execution. We propose an expressive formalism, which allows one to deal with the context-dependent character of clinical guidelines and also takes into account different temporal aspects. We also describe our tool for acquiring clinical guidelines, which provides a user-friendly interface to physicians, and automatically detects many forms of syntactic and semantic inconsistencies in the guidelines being acquired. In the second part of the paper, we describe a flexible engine for executing clinical guidelines (e.g. for clinical decision support applications, for medical education, or for integrating guidelines into the clinical practice), focusing our attention on temporal issues.

Hepatic clearance of D-sorbitol: noninvasive test for evaluating functional liver plasma flow

The hepatic clearance of D-sorbitol, a natural polyol which is metabolized by the liver, was studied in normal and cirrhotic subjects after bolus intravenous injection (2 g) and during constant infusion (54 mg/min) with the aim of providing a noninvasive and simple measure of functional liver plasma flow. The high hepatic extraction of D-sorbitol and the dose-independence of its clearance pointed to a flow-dependent clearance regimen. The renal excretion was taken into account when computing the hepatic clearance. Day-to-day reproducibility of the test was good. No significant difference was found when the hepatic clearance was measured by bolus injection or constant infusion methods. As measured by the bolus injection method, the mean (+/- SD) hepatic clearance in the normal subjects (911 +/- 137 ml/min) was significantly greater (P less than 0.001) than that of the cirrhotics (456 +/- 181 ml/min).The hepatic clearance ofd-sorbitol, a natural polyol which is metabolized by the liver, was studied in normal and cirrhotic subjects after bolus intravenous injection (2 g) and during constant infusion (54 mg/min) with the aim of providing a noninvasive and simple measure of functional liver plasma flow. The high hepatic extraction ofd-sorbitol and the dose-independence of its clearance pointed to a flow-dependent clearance regimen. The renal excretion was taken into account when computing the hepatic clearance. Day-today reproducibility of the test was good. No significant difference was found when the hepatic clearance was measured by bolus injection or constant infusion methods. As measured by the bolus injection method, the mean (±sd) hepatic clearance in the normal subjects (911±137 ml/min) was significantly greater (P<0.001) than that of the cirrhotics (456±181 ml/min).

Adopting model checking techniques for clinical guidelines verification

OBJECTIVES Clinical guidelines (GLs) are assuming a major role in the medical area, in order to grant the quality of the medical assistance and to optimize medical treatments within healthcare organizations. The verification of properties of the GL (e.g., the verification of GL correctness with respect to several criteria) is a demanding task, which may be enhanced through the adoption of advanced Artificial Intelligence techniques. In this paper, we propose a general and flexible approach to address such a task. METHODS AND MATERIALS Our approach to GL verification is based on the integration of a computerized GL management system with a model-checker. We propose a general methodology, and we instantiate it by loosely coupling GLARE, our system for acquiring, representing and executing GLs, with the model-checker SPIN. RESULTS We have carried out an in-depth analysis of the types of properties that can be effectively verified using our approach, and we have completed an overview of the usefulness of the verification task at the different stages of the GL life-cycle. In particular, experimentation on a GL for ischemic stroke has shown that the automatic verification of properties in the model checking approach is able to discover inconsistencies in the GL that cannot be detected in advance by hand. CONCLUSION Our approach thus represents a further step in the direction of general and flexible automated GL verification, which also meets usability requirements.

Combined evaluation of total and functional liver plasma flows and intrahepatic shunting

A diagnostic protocol was studied, designed to evaluate the main parameters of liver circulation in man. A water solution ofd-sorbitol (S) and indocyanine green (ICG) was infused intravenously in six controls and nine cirrhotics. Steady-state renal and hepatic S clearances as well as hepatic ICG clearance were calculated. In controls the values (mean ±sd) of the independent measurements of S and ICG hepatic clearance were 978±107 and 519±142 ml/min, respectively, while in cirrhotic patients they were 554±238 and 231±90 ml/min. Owing to the kinetic properties of S, its hepatic clearance may be regarded as a measure of functional liver plasma flow (FLPF). The total liver plasma flow (TLPF) values (mean±sd), calculated according to Ficks principle, were 1091±157 ml/min (S method) and 1033±153 ml/min (ICG method) in controls, and 1251±554 and 1284±677 ml/min in cirrhotics. In controls, FLPF was found to be very close to TLPF. In cirrhotic patients the difference between TLPF and FLPF (ranging from 169 to 2093 ml/min when measured by S method) was considered as an approximate estimate of intrahepatic shunting. The procedure is safe and simple and may add a new dimension to the investigation of hepatic circulation.

Applying Artificial Intelligence to Clinical Guidelines: The GLARE Approach.

In this paper, we present GLARE, a domain-independent system for acquiring, representing and executing clinical guidelines. GLARE is characterized by the adoption of Artificial Intelligence (AI) techniques at different levels in the definition and implementation of the system. First of all, a high-level and user-friendly knowledge representation language has been designed, providing a set of representation primitives. Second, a user-friendly acquisition tool has been designed and implemented, on the basis of the knowledge representation formalism. The acquisition tool provides various forms of help for the expert physicians, including different levels of syntactic and semantic tests in order to check the “well-formedness” of the guidelines being acquired. Third, a tool for executing guidelines on a specific patient has been made available. The execution module provides a hypothetical reasoning facility, to support physicians in the comparison of alternative diagnostic and/or therapeutic strategies. Moreover, advanced and extended AI techniques for temporal reasoning and temporal consistency checking are used both in the acquisition and in the execution phase. The GLARE approach has been successfully tested on clinical guidelines in different domains, including bladder cancer, reflux esophagitis, and heart failure.

Evidence of an increased nitric oxide production in primary biliary cirrhosis.

OBJECTIVE:Although possible implications of nitric oxide in the pathophysiology of liver cirrhosis have been extensively studied, until now few articles have addressed the assessment of nitric oxide production in primary biliary cirrhosis. This study was directed to evaluate circulating nitrosyl-hemoglobin levels as well as neutrophil elastase and soluble adhesion molecule concentrations in this condition, by assuming these parameters as possible markers of either inflammatory response or neutrophil activation.METHODS:Laboratory investigations were performed in 30 patients with primary biliary cirrhosis, in 13 patients with postviral and/or alcoholic cirrhosis, and in a group of eight subjects with chronic hepatitis.RESULTS:Although no difference was detected with respect to chronic hepatitis subjects, higher levels of nitrosyl-hemoglobin adducts were found in primary biliary cirrhosis patients than in postviral or alcoholic cirrhotics and in normal subjects (3.55 ± 1.75 arbitrary units vs 1.95 ± 0.57 and 0.84 ± 0.34, p = 0.0004 and p < 0.0001, respectively). Similarly, more elevated concentrations of neutrophil elastase (213.7 ± 192.0 μg/L vs 51.1 ± 34.3 and 38.0 ± 11.5, p < 0.0001 and p < 0.0001, respectively) as well as of soluble forms of intercellular adhesion molecule 1 and endothelial-leukocyte adhesion molecule 1 were shown in primary biliary cirrhosis patients than in subjects with cirrhosis of other etiologies and in controls.CONCLUSIONS:Highly enhanced nitric oxide production in primary biliary cirrhosis could be related to the development of strong inflammation and at least partially to neutrophil activation, thus suggesting a putative role of these cellular mediators in the development of liver damage owing to their ability to synthesize and release a wide variety of important factors, including elastase and nitric oxide.

Supporting Knowledge-Based Decision Making in the Medical Context: The GLARE Approach

Knowledge-based clinical decision making is one of the most challenging activities of physicians. Clinical Practice Guidelines are commonly recognized as a useful tool to help physicians in such activities by encoding the indications provided by evidence-based medicine. Computer-based approaches can provide useful facilities to put guidelines into practice and to support physicians in decision-making. Specifically, GLARE (GuideLine Acquisition, Representation and Execution) is a domain-independent prototypical tool providing advanced Artificial Intelligence techniques to support medical decision making, including what-if analysis, temporal reasoning, and decision theory analysis. The paper describes such facilities considering a real-world running example and focusing on the treatment of therapeutic decisions.

A Hybrid Approach to Clinical Guideline and to Basic Medical Knowledge Conformance

Several computer-based approaches to Clinical Guidelines have been developed in the last two decades. However, only recently the community has started to cope with the fact that Clinical Guidelines are just a part of the medical knowledge that physicians have to take into account when treating patients. The procedural knowledge in the guidelines have to be complemented by additional declarative medical knowledge. In this paper, we analyse such an interaction, by studying the conformance problem, defined as evaluating the adherence of a set of performed clinical actions w.r.t. the behaviour recommended by the guideline and by the medical knowledge.

Non-invasive evaluation of portal-systemic shunting in man by d-sorbitol bioavailability

Portal-systemic shunting is an important circulatory abnormality in patients with cirrhosis. This study explores the potential of the natural polyol D-sorbitol as test compound for non-invasive assessment of shunting. Ten normal subjects, 10 patients with cirrhosis and 12 cirrhotics with surgical portacaval shunts were studied after oral and intravenous administration of a 2 g dose of sorbitol. As measured by the H2 breath test, removal from the intestinal lumen was complete in both groups. Bioavailability of sorbitol, calculated as ratio of the areas under the plasma concentration/time curve after p.o. and i.v. administration, was zero in normal subjects, 0.29 +/- 0.15 in cirrhotic patients, and 0.38 +/- 0.11 in patients with portacaval shunts. Calculation of bioavailability on the basis of urinary outputs of sorbitol gave similar results. It is concluded that the bioavailability of sorbitol reflects portal-systemic shunting, although the relatively low figures suggest some degree of sorbitol metabolism by enterocytes.

Clinical guidelines adaptation: managing authoring and versioning issues

One of the biggest issues in guideline dissemination nowadays is the need of adapting guidelines themselves to the application contexts, and to keep them up to date. In this paper, we propose a computer-based approach to facilitate the adaptation task. In particular, we focus on the management of two different levels of authors (users and supervisors), and of the history of the guideline versions.