AUTOMATED MEDICAL DIAGNOSIS WITH FUZZY

STOCHASTIC MODELS:
MONITORING CHRONIC DISEASES
Laurent Jeanpierre and Franois Charpillet
LORIA, MAIA INRIA Team, Campus Scientifique, 54506 Vandoeuvre-ls-Nancy,
France.
Email: laurent.jeanpierre@loria.fr

ABSTRACT
As the world population ages, the patients per physician ratio keeps on increasing. This is
even more important in the domain of chronic pathologies where people are usually monitored
for years and need regular consultations.
To address this problem, we propose an automated system to monitor a patient population,
detecting anomalies in instantaneous data and in their temporal evolution, so that it could alert
physicians. By handling the population of healthy patients autonomously and by drawing the
physicians attention to the patients-at-risk, the system allows physicians to spend
comparatively more time with patients who need their services. In such a system, the interaction
between the patients, the diagnosis module, and the physicians is very important. We have based
this system on a combination of stochastic models, fuzzy filters, and strong medical semantics.
We particularly focused on a particular tele-medicine application: the Diatelic Project. Its
objective is to monitor chronic kidney-insufficient patients and to detect hydration troubles.
During two years, physicians from the ALTIR have conducted a prospective randomized study
of the system. This experiment clearly shows that the proposed system is really beneficial to the
patients health.

Keywords: Stochastic processes, diagnosis, fuzzy filters, medical monitoring.

1. INTRODUCTION
The DIATELIC project
The automated monitoring of chronic renal diseases is an interesting application of
artificial intelligence techniques to the medical field. Actually, as modern treatments
enhance the medical care for kidney troubles, dialysed patients expected lifetime
increases dramatically. Combined with the global aging of the population, this
worsens an already important shortage of nephrologists. Therefore, typically patients
are having to wait their turn before they can be healed.
In order to enhance this situation, in France, the LORIA (research laboratory in
computer science) and the ALTIR (Lorraines association for the treatment of renal
insufficiency) have funded the Diatelic project. With this system, patients are able to
send their medical data through the Internet on a daily basis. Then, a dedicated
computer can analyse these data in real time and compare their evolution with the
Acta Biotheoretica 52: 291311, 2004.
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2004
Kluwer Academic Publishers. Printed in the Netherlands.

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patients profile. Finally, when an abnormal situation is detected, the system sends an
alert to the nephrologists of the ALTIR.
At this moment, physicians are able to consult all the archived data, the diagnosed
evolution of the patient, and messages from the patient. From this point, they can
make their own diagnosis, convoke the patient for further analyses, or adapt the model
to this particular patient to conform to particularities and evolutions.

Tele-medicine, a transversal approach

Currently, there are four main approaches studied in the context of computer-aided
medicine: remote consultations (Chen et al., 2001) which enables a physician to make
a diagnosis on a patient without being physically present, itinerant medical profiles
(Shortliffe, 1998; Kosh and Slota, 1999) which enables specialists to access data they
need from anywhere, the automated diagnosis or monitoring of patients (Huang, 1999;
Chen et al., 2002a), and knowledge discovery in databases (Keravnou et al., 2000;
Chen et al., 2002b). We could also consider remote surgery, but its domain is different
from the others since the computer has no real influence on the patient.
Our approach of tele-medicine is slightly different since it combines some aspects
of all these branches: some simplified form of remote consultation, a patient profile,
and an automated diagnosis module. The article by Bellazzi and Magni (2001) shows a
system that is very close to ours, but it seems to be some very preliminary work.
Network aspects of the Diatelic project have been studied by Bellot et al. (2001).
In the current article, we will focus on the diagnosis module which could be classified
in the third branch: intelligent analysis of medical data. However, the fact that our
patients stay at home implies variations to other approaches. In particular, data are
available only once a day; moreover, they are far less reliable, since the patient
measures all his signals himself. Additionally, no stepwise diagnosis (Groselj and
Kukar, 1999) is possible because the patient is not at the hospital: since one of the
objectives is the cost reduction so that the system could be widely used, convoking the
patient for further analyses should be avoided as much as possible.
The originality of our system resides in the way it is built. Usually, models are
based on the data they are to monitor. We have based our system on the medical
situations the physicians want to detect, whatever the actual data might be. Moreover,
since we only assist the nephrologists in their work, a black-box approach is not a
solution. In order to provide them with a meaningful tool, they must be able to
integrate the system in their daily practice. This dictates several limitations upon
available models. The complete description of this work is available in Jeanpierre
(2002).
Since the year 2000, nephrologists from the ALTIR have used this system every
day with some of their patients. First, they conducted a prospective randomised study
with 30 patients for two years. Since the results are really encouraging, this will be
extended to a greater population containing up to 150 patients.
Firstly, we will describe the diagnosis objectives, focusing more precisely on the
medical implications of our choices. Next, we will explain the nature of the available
signals, and their relationship with the situations we are to diagnose. This leads
naturally to the patient model we implemented, along with its presentation to the
medical team. The following section will focus on the diagnosing algorithm which

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allows for computing the medical state of the patient from the daily data he sends.
Finally, we will show the prospective experiments conditions, its results, and some
feedback we obtained from the physicians and their patients. We will conclude with
considerations for developing the system in order to provide patients and nephrologists
with an even better tool.

2. DIAGNOSIS CONSIDERATIONS
The medical situation
The Diatelic project aims at monitoring chronic renal insufficient patients treated
through continuous ambulatory peritoneal dialysis (CAPD). This treatment allows the
patients to operate their dialysis at home; this way, they can keep a normal life despite
their illness. To achieve their treatment, they only have to fill their peritoneum with a
dialysis solution three to four times a day through a catheter, surgically-added at the
lowest end of the peritoneum.
With this treatment, the patient can replace some of the kidneys functions. In
particular, the renal insufficient patient quickly loses the purification functions, along
with hydration regulation capabilities. Since the peritoneum is very well irrigated by
small blood vessels, osmosis and diffusion are able to occur between the blood stream
and the peritoneum content. This natural phenomenon tries and equilibrates
concentrations on each side of a semi-permeable membrane like the peritoneum.
Hence, toxins progressively leave the patients blood to fill his peritoneum.
Simultaneously, water will be drained at a rate depending on the dialysis solutions
concentration.
CAPD generally is a good replacement for haemodialysis, because it allows
patients to keep their autonomy and does not require them to spend three days a week
in a dialysis centre. Additionally, it requires fewer medical staff to achieve a similar
result. This point is, from a purely medical point of view, the advantage and the
drawback of this method. Actually, as the population ages, the number of patients per
physician rapidly increases. This is even more critical if we consider specialists who
are nephrologists. Moreover, as medicine enhances the quality of treatments, patients
live longer. Thus, CAPD is a real improvement over haemodialysis, since more
patients can be healed with the same number of nephrologists and nurses.
In France, approximately 10% of chronic renal insufficient patients use peritoneal
dialysis techniques, i.e. at least up to 2000 patients. Moreover, this number increases
by 7% each year.
However, since patients operate their dialysis on their own, their situation is
riskier. The classical approach states that each patient has to come and see his
physician once a month. Between two visits, each patient regulates his treatment
thanks to simple rules given by the nephrologists: if your weight exceeds 70 kg, use a
HYPER night bag. Obviously, if the patient feels bad, he can phone to have his
treatment adapted. In addition, nurses come and see some of the patients from time to
time. Obviously, the patients are more at risk than those treated by haemodialysis,
since their treatment does not take place at the hospital.
In particular, patients troubles are principally related to hydration problems: if the
dialysis is too weak, the amount of water in the patients body keeps on increasing and

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he quickly enters hyperhydration. This pathology is insidious, because the patient

shows few external signs of illness; he seems healthy to anyone except to physicians
and nurses. Internally, hyperhydration has catastrophic consequences: the blood
pressure (BP) quickly increases and begins damaging all the vital organs, and
especially the kidneys. In this case, renal insufficiency quickly worsens to a state
where no residual function exists. The kidneys just stop working. Ultimately,
hyperhydration leads to the formation of edemas, which are usually deadly if not
healed in time.
Alternatively, when the dialysis is too strong, the patient simply dehydrates
himself. Ultimately, this may lead to coma and death, because the organism has not
enough water left to enable the simplest vital operations. This is not so dramatic, since
a dehydrated person feels and looks bad: the patient knows he needs some healing.
Other troubles exist. In particular, the risk of infections is rather important since
the catheter directly links the peritoneums content with the exterior. Normally, the
catheters sterility is ensured by the cautious use of adapted tools. However,
manipulation errors often induce bacterial or viral infections, directly into the
peritoneum. This may lead to serious complications like peritonitis. However, even if
this kind of accident is frequent, complications are usually avoided thanks to an
adapted medical treatment.

The systems objectives

The Diatelic system aims at improving this problematic situation by providing a
daily analysis of each patients data. The objective of the module is to alert the
medical team when a patient shows an abnormal behaviour. Since the major risk for
CAPD patients is related to hydration troubles, we have focused on the evaluation of
this variable. Thus, the main objective of the system will be to ensure that each patient
keeps his hydration normal. The trouble is that normal is a subjective interpretation.
Even more important, this value is not measurable directly. We will have to deduce it
from the evolution of the available medical signals.
To regulate the patients treatment, nephrologists compute an ideal value for the
patients weight. This value represents a standard condition, the patient showing a
good equilibrium of bones, muscles, fats and water. Obviously, this is very dependent
on the patient morphology. If he loses weight or if he grows fat, his ideal value must
be adapted to cope with this evolution. If the ideal weight of the patient is perfectly
known, evaluating his hydration is easy: if his weight is over his ideal weight, the
patient tends to a hyperhydrated state. This is also true with a lower weight and a
dehydrated condition.
Finally, the problem can be summarized by these two questions: Is the ideal weight
correctly set? What is the patients weight with respect to its ideal value? To answer
these questions, we only have a set of medical signals the patient sends every day.
Each signal is related to both questions.

The available medical signals

Each day, a CAPD patient completes a form with medical data. Within Diatelic,
the paper sheet is replaced by a computer form, but the requested data are exactly the

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same. The only difference is that the entered values are transmitted directly to the
physicians office instead of waiting for the next consultation.
These data include the patients weight, his temperature, some blood pressure
measures, and dialysis configuration. In this section, we will detail each signal, along
with its relationship with our goal and the way it is acquired.
Weight
The patients weight is measured by simple domestic weighing-scales every day.
This value depends on several parameters, since every part of the organism adds to the
total weight. Major contributions are linked to bones, muscles, fats and water. The
influence of the first three is obvious; however, we are really interested in the
influence of the last one: water. Simple physics tells us that one litre of water weighs
one kilogram. This implies that hydration has a direct impact on the weight.
However, except for bones, the contribution of the patient morphology may vary
through time, since patients are monitored for very long periods. To isolate the water
contribution to the global weight, nephrologists use the ideal weight as a reference
value. Compared to this value, any weight evolution is directly related to variations of
the patients hydration.
When the patients morphology evolves, so do his ideal weight and our reference.
Hence, this signal is not sufficient to determine if the observed variations are related to
hydration troubles or morphology modifications.
Blood Pressure
Blood Pressure (BP) is measured by the patient himself or by nurses if the patient
is not able to achieve a proper measure. Since the patient population is relatively old,
this measure is somewhat biased because of the progressive deafening that generally
occurs with ageing. However, we are more interested in BP variations than in its raw
values. Therefore, a fixed bias is not a real trouble in this case; we simply observe
higher values when they are measured by the patients.
BP is directly related to hydration, since the blood volume depends on the amount
of water it contains. Hyperhydration implies some blood volume increase, which
implies a BP augmentation. The opposite is true also for dehydration and BP decrease.
For this reason, monitoring the BP variations gives very reliable clues about hydration
variations. This explains also why raw values have little importance.
Moreover, BP evolves as the patients position changes. In particular, when the
patient stands up, BP normally increases slightly to cope with gravity, in order to
irrigate the upper part of the body. However, when the patient dehydrates himself, this
phenomenon disappears. At this time, the upper bodys BP decreases quickly and may
lead to losses of consciousness. This is why each patient measures his BP when he is
lying down and a second time just after standing up. The difference of these values is
known as orthostatic blood pressure. Orthostatic hypotension is a very strong
dehydration indication. It is quite reliable, since it does not depend on variations of the
raw BP values. There is no need for a reference value to evaluate it. However,
hyperhydration has no influence on this.
The trouble with BP is that it does not depend on the hydration level only. The BP
regulation is ensured by the heart and by muscles positioned around blood vessels.

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Any modification of these systems may modify the way BP evolves. In particular,
patients suffering from heart diseases or insufficiencies show different schemas of BP
evolutions with respect to their hydration. The good point is that these parameters
rarely evolve. However, in our clinical experiment, we have observed at least one
patient who needed a profile modification because of a heart disease recovery.
Temperature
Temperature is measured by a simple medical thermometer. This signal is
relatively worthless for diagnosing hydration troubles, since we know no relationship
linking its value to the amount of water the patients body contains. At most, we could
use it as a witness of some infection. Even then, its utility would need to be proven.
Ultrafiltration
Peritoneal dialysis is achieved by filling the patients peritoneum with some
dialysis solution, keeping it in stasis for several hours, and then flushing it before
starting a new cycle. Before its injection, the dialysis solution is weighed. After being
flushed, it is weighed again, so that we can compute the weight difference, named
Ultrafiltration.
This difference represents the throughput of the dialysis. During the stasis, the
process equilibrates progressively the concentrations of the peritoneums dialysis
solution and the blood contained in the vessels which irrigate its membrane. Even if
the process is complex and several materials are exchanged during this period, the
global weight difference is relatively predictable for a given patient. In fact, the
principal contribution to this value is the drained water. Toxins extracted from the
blood typically are negligible, compared with the amount of water containing them.
Therefore, this value can be seen as an indicator of the amount of water contained
in the blood stream. Actually, the more water the blood will contain, the less
concentrated the blood will be, and the more water the dialysis will drain.
However, the clinical study seems to indicate that this value is not reliable. In fact,
it would be an interesting indicator of the quality of the peritoneum membrane, which
is progressively damaged as time passes. According to nephrologists from the ALTIR,
the relationship between hydration and ultrafiltration is really thin, and should not be
taken into account.
Automated measures
The question of acquiring these data automatically has been discussed, since
several existing technologies allow for such an acquisition. However, physicians
prefer avoiding this solution, because of the psychological effect on the patients: They
think that since measuring their physiological signals involves the patients in their
treatment, they will better obey their physicians directives.

3. THE COMPUTER MODEL

Several ways of modelling such a problem within a computer exist. In particular,
we tried two approaches: a rule-based expert system (Buchanan and Duda, 1982) and a
Hidden Markov Model (HMM). These two modules are based on the nephrologists

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knowledge of the hydration influence on the different medical signals available. Their
objectives are to identify patients troubles before they become life-threatening, and to
figure out if the observed deviations are related to hydration evolution or to some
modification of the patient morphology. The principles of these two models are
different, but they are based on the same observations.
Therefore, we will describe firstly the observations of the diagnosing modules;
then, we will briefly describe the rule-based system along with its drawbacks before
showing the HMM which has been used for several years in Diatelic.

Fuzzy observations
The observation function is based on a computers design limitation: computers are
discrete, i.e. any symbol a computer manipulates can have a finite number of values.
There is no possibility of creating really continuous values. The trouble is that almost
all we observe has a continuous value. For example, weight, BP, and so on.
There exist two main approaches to this problem. The first one uses a set of
discrete values to represent a continuous one. In most cases, it is a valid approach,
since it needs only an adapted set of symbols. For example, we could discretise the
weight by using a symbol for each integer value: 60, 61, 62 kilograms. Within this
model, 60.3 kg is not a valid weight; it will be rounded to 60 kg. The error amplitude
is inversely proportional to the number of the available symbols: if more precision is
needed, using a symbol for each 100 gram slice will be sufficient. The trouble is that
the model should express the relationship between these symbols and the underlying
state the system is to diagnose. This implies that the nephrologist who is responsible
for introducing a new patient in the system is to state this relationship for all the
possible sensors values. This quickly becomes impossible as the symbols set grows
bigger.
The second approach consists of using parametric curves to model the influence.
This kind of model is very useful where the influence we are to model has a known
structure. For example, in speech recognition, the classically used pattern is a mixture
of Gaussian probability distributions. However, this typically leads to huge parameter
lists, and their precise influence is difficult to describe. Hence, this approach is hardly
compatible with a full-scale interaction with physicians.
To resolve this problem, we chose a hybrid approach through the fuzzy filtering of
the medical signals as suggested in Steinmann (2001). To be precise, we decided to
model each sensor as a fuzzy value that can have few symbolic values. Since we
consider long-term monitoring of chronic diseases, there exists a central condition that
represents a healthy situation. Therefore, in order to closely map the model with the
physicians way of describing their diagnosis rules, we chose a set of three values for
each sensor: low, normal, and high.
For example, since nephrologists usually give rules such as if your weight is high
(> ideal weight + 1.5 kg), use a HYPER dialysis bag, our weight sensor will be based
on the ideal weight value. If it is lower (respectively higher) by at least 1.5 kilograms,
the patients weight will be considered as low (resp. high).
The trouble is that this implies an annoying threshold effect: if we consider an
ideal weight of 60 kg, 61.4 kg is normal, but 61.5 kg is high. In turn, this implies
strong variations in the diagnosis because of brutal variations of the available data. To

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prevent this threshold effect, we used fuzzy filtering: the system will map a given
sensor value to a confidence distribution over the symbols instead of returning a single
symbol. In the previous example, 61.4 kg will be 8% normal and 92% high. This
smoothes the diagnosis rules and almost removes the threshold effect. In particular, it
enables the system to compensate for the influence of several sensors. For example, if
the weight is 60% high, but other sensors have normal values, it will be less important
than a situation where BP would be high also, even by a mere 30%.
We tried and compared the two approaches, i.e. with fuzzy filters and without
them; the results show a real enhancement with fuzzy filtering. Diagnoses are
smoother and they vary less when we add some noise to the systems input values. The
last question of importance is the way fuzzy filtering can be achieved. We worked
from simple considerations to define the right parametric curves for each symbol.
First, this function must reach its boundaries. For example, a weight that is
10 kilograms over its ideal value is clearly high. There is no chance it could be
considered low or even normal. The next point is that the confidence is not linear. For
a given increment, the influence will depend on the base value of the sensor. The idea
is that the reference value is not perfectly known, so it is useful to have the smallest
possible variations around this value. With these constraints, the usual functions, i.e.
exponential and linear functions, cannot be applied to our system.
Thus we decided to define the relevant function from its constraints by using a
mere interpolation function on a given interval. The low symbol (resp. high) is
defined by four constraints: it is 100% at its lower (resp. higher) boundary, 0% at its
upper (resp. lower) boundary, and it has a zero derivative in these points. The simplest
formula that allows such constraints is a polynomial with four degrees of liberty:
Low (x) = 3x2 + 2x3 x [ 1;0]
(1)
High (x) = 3x2 2x3

x [ 0;1]

Normal (x) = 1 (Low (x) +High (x)) x [ 1;1].

(2)
(3)

For the sake of simplicity, these formulas have been computed with a reference
value of 0 and interval amplitude of 1; however, we can transpose them to any other
values thanks to equation (4). Outside of their definition interval, each symbol has a
fixed probability equal to its value at the corresponding terminal. Normal is simply
defined as the complement of the two other symbols.

x=

sensor reference
.
amplitude

Figure 1. Graphic representation of our fuzzy symbols.

(4)

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299

For example, if 60 kg is a normal weight, 60.1 kg will be 97% normal with

standard amplitude of 1.5 kg. 60.2 kg will be 90% normal, and 60.3 kg will be 78%
normal only.
The fuzzy filters actually enables the model to express the relationship between the
medical state of the patient and the sensors values with relatively few parameters.
Moreover, the physicians can easily interpret each parameter, because their values are
directly expressed in a human-readable form. The clinical experiment we conducted
clearly shows that nephrologists from the ALTIR are able to work with this model
with a very short adaptation period. After a few days they are able to tune a model for
any patient and they can interpret a patients profile with little effort.

A rule-based expert
Since the MYCIN system showed good results (Buchanan and Shortliffe, 1984),
the first module we built was based on a rule-based expert system. Actually, this kind
of computer module is able to select and apply rules from a set of predefined ones to a
set of facts. In our problem, we used CLIPS, a generic rule-based system initially
developed by the NASA since 1984.
More precisely, we used Fuzzy CLIPS, which is a newer version that permits the
use of fuzzy logics. Therefore, it is clearly well adapted to our perception model. The
system will work from the insertion of a daily fact that includes all the medical signals
of a given patient. At this moment, rules are gradually applied to process these raw
data, and produce high-level knowledge: the desired diagnosis.
After some tuning, the system was able to produce very good diagnoses for a given
patient. However, it required that we set the proper values for thresholds, rule
priorities, and influences. Therefore, we could not apply this system to a whole
population of patients. In fact, there were so many parameters to set for each patient
that several days of trials were necessary before obtaining the proper parameter
combination. Additionally, no one was able to understand the exact implication of a
single parameter value anymore. Therefore, the system became a black box that
sometimes produced relevant diagnoses. Obviously, it was not compatible with a daily
interaction with the physicians anymore.

The stochastic model

As stated in Horn (2001), it is necessary to evolve from a knowledge-based to a
data-based system to achieve a good medical diagnosis. In fact, this amounts to
admitting that our knowledge is neither complete nor perfect. By focusing on the raw
data, we try and deduce relations on observed facts rather than to explain how these
observations are produced by the organism.
Regarding the definition of the module, this approach is totally different. In RuleBased systems, we have to formally express diagnosis rules. With a Data-Based
system, we state the influence the diagnosis has on the sensors; this declarative
knowledge is far easier to gather and formalize.
In the vast family of numerical models, we decided stochastic models should be
the best bet to cope with both the uncertainty of our knowledge and the noise that may
influence the system. More precisely, we chose Markov models, because of their
ability to model temporal evolutions of dynamic systems. Moreover, these models

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have been studied for years, and we know very efficient algorithms to handle their use
within a computer.
The Mathematical Formalism
A Markov model is a finite state automaton with probabilistic evolution which can
be specialised into several models: Hidden Markov Models (HMM), Markov Decision
Processes (MDP), and Partially Observable Markov Decision Processes (POMDP).
We chose the last one, which is the more potent but also the more complex. However,
we use only a small part of its possibilities; in particular, we may study the planning
operations in future extensions only.
A POMDP is a structure (S, I, O, A, B, R):

S:

I :
O:

A:
B:

R:

a finite set of discrete sets,

a finite set of discrete influences,
a finite set of observable symbols,
a transition function A: S I ( S),
an observation function B: S (O),
a reward function.

(5)

In this structure, the set of states has a central role: it represents the hidden state of
the modelled system, the state which dictates the system behaviour. The Markov
hypothesis states that the knowledge of this state gives the knowledge of all the future
system evolutions and observations, with no additional information requirement.
The transition function is a probabilistic description of the system evolution: for a
given action used in a given state, it predicts the distribution of states the system will
reach on the next step. The classical way to implement such a function consists of
using a S S probabilistic matrix for each possible action.
The reward function is a way of indicating the goal we would like the model to
reach. Several forms of rewards exist, depending on the relative importance of states,
actions and observations. As we focus on passive diagnosing (nephrologists are
responsible for the patients treatment), the system does not need to choose a
therapeutic action. The computers role is limited to monitoring patients and alerting
physicians. Therefore, we will not detail the reward subtleties.
The observation function is another probabilistic function which describes how the
model state is hidden by the observation process: The systems state is not directly
observable, but there exists a set of observable symbols which are influenced by the
systems state. The trouble is that this influence is not perfectly known and its
measurement may be spoilt by noise; this is why this function is probabilistic.
Anyway, these symbols are the only available data.
Considering the observation model we described earlier, continuous medical
signals are transformed into confidence distributions among sets of three fuzzy values
notated -, = and +. Therefore, we decided to use the approach described in
(Koenig and Simmons, 1996): considering a sensor c, its observed value c(O) is
projected onto its fuzzy symbols, and the resulting confidence vector is aggregated
into a probability vector. Each component of this vector is the probability of observing
the continuous sensors from a specific state:

AUTOMATED MEDICAL DIAGNOSIS WITH FUZZY STOCHASTIC MODELS

P( c (O) | s) =

P( c (O) = v) P( c = v | s).

301
(6)

v { , = , +}

This is possible only if each sensor is considered as statistically independent from

the others, depending only on the models state. Next, we can aggregate the
probabilities for observing each sensor c in a single observation probability for each
state to obtain our observation function:

P(O | s) =

P(c(O) | s).

(7)

Finally, the description of the influence of the models state on a given sensor will
require only three probabilities per possible state. Once again, we can use a matrix per
sensor to store these probabilities.
Application to medical diagnosis
There are two principal applications for POMDP: localization and planning. The
former consists in searching an optimal sequence of actions to reach a given goal.
Since the goal is expressed through the reward function, this is equivalent to finding
the action sequence which maximizes the expected reward. Localization consists of
trying and figuring out the hidden state of the system, using the available knowledge
(the model) and the observed data.
Since we focused on the diagnosis problem, we obviously chose the localization
problematics; the planning functions will be studied in future work. From the
dictionary, diagnosing is determining a disease from symptoms. On the other hand,
localization is defined as to position in space. Hence, these two notions are very
similar. To achieve medical diagnosis with localization algorithms, we simply defined
an ad hoc space: our POMDP state space is based on a map of pathologies. Therefore,
positioning the patient on this map is equivalent to determining the pathologies it
suffers from.
Considering our particular problem, the long-term monitoring of patients, we have
a special state that plays a central role in the system: the healthy condition. Normally,
any patient should be in this state, where all is right and there is no particular risk.
From this point, we can derive variations, based on the possible appearance of some
pathology. We decided to focus on hydration troubles, since they represent the
principal risk for CAPD patients. As we stated in the observation-related section, the
setting for the ideal weight has a crucial role in the regulation of the dialysis strength.
Since one of the main hydration indicators is the weight and this sensor is evaluated
with respect to its ideal value, the evaluation of the pertinence of this setting has been
elected as an interesting point to diagnose also.
Finally, our model states will spread across two axes: hydration and ideal weight.
Considering our problem, we chose to model these variations in the same fashion as
sensors: hydration may be normal (=), low (-) or high (+). Therefore, the healthy
state will be notated (=, =): normal hydration with a correctly set ideal weight.
From the analysis of the available medical signals, we can isolate four useful
independent sensors: Weight, Blood Pressure, Orthostatic Blood Pressure (OBP) and
Ultrafiltration (UF). Each one is related to hydration troubles in a known way.
Obviously, Ideal Weight is only related to the weight sensor. Other sensors may be

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influenced by the couple Weight/Ideal Weight, but we assumed our sensors are
independent of one another. Therefore, this relationship will be modelled through the
model state: hydration and Ideal Weight influence the perception of the weight, BP,
OBP and UF. Table 1 shows the direct relationship between the fuzzy perceptions and
each possible disorder, considered as the only influence.
Table 1. Disorders influence on sensors.

Sensor
Disorder
+/=
-/=
=/+
=/-

Weight

BP

OBP

UF

High
Low
Low
High

High
Low
Normal
Normal

Normal +
Low
Normal
Normal

High
Low
Normal
Normal

Table 2 shows the resulting influence of the combination of both disorders;

obviously, we can see that some combinations are difficult to diagnose. These are
referred as High&Low since one disorder usually comes with a high sensor reading,
whereas the other one implies a low sensor reading. The actual value can be almost
anything since it depends on the relative strength of both disorders. One of them can
dominate the other one, or both influences can bring an artificially normal reading. For
this reason, we decided not to include these two states into our state space. Finally, our
model will use five states: healthy, hyperhydration, dehydration, Ideal Weight
High and Ideal Weight Low.
Table 2. Combined influences of two disorders.

Sensor
Disorder
+/+
+/-/+
-/-

Weight

BP

OBP

UF

High&Low
High
Low
High&Low

Normal +
Normal +
Normal Normal -

Normal +
Normal +
Normal Normal -

Normal +
Normal +
Normal Normal -

In the current version of the Diatelic system, no action has been implemented.
Actually, the actions represent the known influences a given patient will receive
during the considered time lapse. Concerning CAPD patients, these influences contain
but are not limited to dialysis strength and drugs consumption. In general, to modify
the dialysis strength, a patient can use various concentrations of dialysis liquid.
Usually, they use three kinds of standard bags: ISO, MEDIUM and HYPER. ISO bags
have a concentration which is comparable with the human blood; thus, they should
drain almost no water at all. On the other side, HYPER bags are much more
concentrated. Such a bag is used to drain much water. MEDIUM bags have an
intermediate concentration and effects.
A given patient uses 3 bags a day, each bag staying in stasis for 4 hours in the
peritoneum. Some patients use an additional bag during the night. Hence, we can have

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303

at most (3^3)x4 = 108 different dialyses. Moreover, each patient reacts to a particular
treatment differently from the other patients. Finally, there are several noise sources
that perturb the standard evolution of the patient: stress, ambient temperature, and
meals are common sources which are totally uncontrolled since the patient is at home.
All these facts made it impossible to learn a complete set of actions for each patient.
Finally, we chose to implement a generic action which includes no influence, but
ensures the temporal coherence of the diagnosis: for example, a patients hydration
will rarely evolve from a leakage to an excess in a single night. The action we
modelled will make such an evolution very improbable.
Currently, a patient profile will contain only 60 probabilities, along with a few
computed tendencies like the average BP measured during a few days. These
probabilities are the parameters of the observation function: we have four sensors with
three fuzzy values influenced by five states. Since the fuzzy values are used through
confidence distributions, one third of these probabilities can be deduced. Finally, a
patient profile will contain 40 independent parameters.

Healthy

Dehydration

Hyperhydration

I.W. Low

I.W. High

Weight

BP

OBP

UF
Figure 2. Diatelics observation function.

Since our sensors are independent, it is possible to plot the probability of the
observation of each sensor within each state of the model. The resulting graphs,
represented in Figure 2, show intuitively the influence of each state on the various
sensors. Physicians can dynamically interact with this representation by dragging the
curves with their mouse. At this time, the program automatically computes the new
model, and displays the updated diagnosis. This way, nephrologists can adapt the
profile to their patient.
Considering our model definition, the semantics of each parameter is obvious. In
the same fashion, anyone could interpret the diagnosis without difficulty: The
localization algorithm (Forney, 1997) computes a probability distribution over the
states for each time data have been received. Since we fixed the medical semantics of
each state, imposing a strong relationship with the possible occurrence of troubles, we

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can interpret these distributions directly as the probability of the corresponding

troubles. We tried several ways of displaying these voluminous data (five daily
probabilities), but we finally elected the simplest one: for each patient, a graphics
displays a set of five plots, one per state. Each plot has a specific colour which
identifies it from the others. The nearer from the top of the display a plot is, the more
probable the associated state is.

Figure 3. Sample diagnosis from Diatelic.

Figure 3 shows a sample diagnosis computed during a dehydration incident. At the

beginning of this period, the patient was healthy. After a few days, some gradual
dehydration (plotted in black) appears. When the black plot becomes dominant, an
alert is sent to the physician who adapts the patients treatment. In the few following
days, the healthy state becomes dominant again, we certainly avoided an accident.
Shortly after the dehydration peak, we can observe a small increase of the Ideal
Weight High plot. This is due to the patients BP which returned to its normal value.
At this time, the weight is over its ideal value, and other sensors are almost normal.
This situation is characteristic of bad ideal weight setting. However, as these
conditions are transient, and since the other sensors are slightly over their normal
value (in their tolerance interval), this state never becomes a real hazard. It remains a
mere possibility.

4. THE DIAGNOSING ALGORITHM

As we showed in the previous section, computing the patients diagnosis is
equivalent to determining the probability of each model state at each time step. This
can be efficiently computed thanks to the application of Bayes rule for conditional
probabilities (equation (8)) and dynamic programming principles (Puterman, 1994).
The resulting algorithm, Forward-Backward, has been published in Forney (1997):
P(A.B) = P(A | B) . P(B) = P(B | A) . P(A).

(8)

At the time t, the patients diagnosis is the vector which contains the probability
of each state st, knowing the observation sequence O and the model :

AUTOMATED MEDICAL DIAGNOSIS WITH FUZZY STOCHASTIC MODELS

t ( q) = P( st = q | , O) .

305
(9)

The application of Bayes rule allows for isolating the observations from the
model:

t ( q) =

P( s t = q , O | )
.
P(O | )

(10)

The observation sequence can be split at time t:

t ( q) =

P( s t = q, O | ) P(Ot +1...T | s t = q, )
.
P(O | )

(11)

The introduction of the parameters and will simplify the equation:

t ( q) = P(O1...t , st = q | )

(12)

t ( q) = P(Ot +1...T | , St = s)

(13)

t ( q) =

t ( q) t ( q)
.
t ( q' ) t ( q' )

(14)

q 'S

The computation of is known as the forward procedure, while computing

relies on the backward procedure. The first step of the forward computation relies on
the application of Bayes rule once again:

t ( q) = P(Ot | , O1...t 1, st = q) P(O1...t 1, st = q | ).

(15)

The first term is the simple application of the observation function B to the state q,
since the Markov hypothesis allows us to drop all the previous observations. The last
term can be detailed, depending of the state at the time t 1:

t ( q) = B(Ot , q) P(O1... t 1 , s t = q, s t 1 = q' | ) .

(16)

q 'S

A new application of Bayes rule will enable the summed term to be split:

t ( q) = B(Ot , q) P( s t = q | , s t 1 = q' )P(O1.... t 1 , s t 1 = q' | ).

(17)

q 'S

The first term in the sum is the mere application of our transition function to the
states q and q, and to the action at - 1. The last term is simply the expansion of at the
time t 1, in the state q:

t ( q) = B(Ot , q) A( q, at 1 , q' ) t 1 ( q' ).

(18)

q 'S

This expression is simple enough to be computed with a complexity linear in time

and in the cardinality of S S . We will have to work similarly with equation (13):

t ( q) = P(Ot +1...T | , St = s) .

(13)

In order to allow for the appearance of a recursive form, we will expand this
expression, depending on the state at time t + 1:

t ( q) = P( s t +1 = q' | , s t = q) P(Ot +1...T | , S t +1 = q' ).

(19)

Once again, the first term is the application of the transition function to the states q
and q, and to the action at.

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t ( q) = A( q' , at , q) P(Ot +1...T | , S t +1 = q' ).

(20)

q 'S

From this point, we can split the observation sequence again, so that the time t + 1
is separated from the others:

t ( q) = A( q' , at , q) P(Ot +1 | , S t +1 = q' ) P(Ot +2...T | , s t +1 = q' ).

(21)

q 'S

The last term is merely the expansion of , applied at the time t + 1 and the state
q. The central term is simply the application of the observation function B to the
symbol observed at time t + 1 and to the state q:

t ( q) = A( q' , at , q) B(Ot +1 , q' ) t +1 ( q' ).

(22)

q 'S

Since this functions complexity is also linear in time and in S S , so is the

complexity of our diagnosis computation, . Finally, since our state space is relatively
small, this complexity is acceptable and allows for a real-time analysis of data.
Obviously, computing the diagnosis of a given patient for several months has little
interest and becomes costly concerning the necessary computing time. Hence, we
limited the computation to the latest 60 days: at any time, physicians can have a look
at the computed diagnoses for the last two months.

5. THE PROSPECTIVE EXPERIMENT

Conditions
The Diatelic analysis module has been studied in a monocentric prospective
randomised experiment which lasted two years. This study included 30 voluntary
patients who were suffering from terminal chronic renal insufficiency. The objectives
and the conditions of the experiment have been explained to all patients, who accepted
them. All these patients have been treated through standard CAPD for one month at
home after being equipped and trained by nephrologists from the ALTIR.
After this month of formation, patients were randomly distributed across two
populations: the Diatelic and the Reference groups. The first group has been
monitored with the module this article describes while the other one was monitored
the classical way. The first patient entered the experiment on 6th June 1999. The latest
entered on 8th August 2000. The global study ended in August 2002, two years later.
The objectives of the study were to find out the impact Diatelic has on the patients
life quality, their morbidity, and the global treatment cost.
Table 3. Group characteristics.

Group
Sex (Men / Women)
Average age (standard deviation)
Diabetic patients
Comorbidy (Charlson Index)
Distance from the ALTIR in km

Diatelic
8/7
69.8 (14.8)
5
5.7
52

Reference
9/6
70.7 (12.4)
4
4.8
52.5

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307

Gladly, the two groups are statistically comparable. Significance is evaluated

through a standard ANOVA (analysis of variance) statistical test. Table 3 shows their
compared characteristics. The Charlson Index is an evaluation of the illness severity
based on the age and pathologies, ranked with respect to their mortality. These
characteristics show no significant difference between the two groups. More than these
numerical values, medical causes for the renal insufficiency and residual kidney
functions are also statistically comparable across the two groups.

Results
At the end of the experiment, results have been gathered and new data will not be
included. However, since the intuitive evaluation of the system by the patients and
their nephrologists was very positive, the experiment continued from then. All the
results are not known yet. In particular, the study of the life qualitys forms is not
complete. However, the results we expose here are really positive. After six months,
the first medical enhancements were already discernible by the medical team
(Chanliau et al., 2000).
To begin, we will consider the compared mortality: the study included 30 patients;
on 8th August 2002, 12 patients were still in the groups. Table 4 shows the reasons for
the departure of the 18 other CAPD patients, but none of these causes are statistically
significant. In particular, the number of deceased patients seems prohibitive. However,
none of these deaths is related to dialysis troubles, and this should not be counted
against our system. Moreover, the average Charlson index is very high in both groups
and patients are quite old; since these two factors amount to a low survival rate
(Charlson et al., 1987), this high death percentage is not really surprising.
Table 4. Reasons for patients departure from the experiment.

Reason for departure

Deceased
Transferred to haemodialysis
Geographic movement
Kidney transplant

Number of patients
Diatelic
Reference
8
4
3
1
0
1
0
1

The first significant factor the study reveals deals with the number of visits each
patient pays to his nephrologist. The normal frequency of a patients visits is once a
month, i.e. 12 in a year. However, the delay between two visits is decided by the
physician, depending on the health level of the patient. Table 6 shows the comparison
of the visits frequency with respect to the fact of whether the patient died or not, which
is a crude but objective indicator of the patients health level. As expected, unhealthy
patients come and visit their physician more often. On the other hand, Table 5 shows
the compared value of the two groups, indicating both the average value and standard
deviation of consultations and hospitalizations. The number of normal visits is almost
the same for both groups, but spontaneous visits show a very significant
(PANOVA < 0.0066) drop in the Diatelic group with respect to the Reference group.

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Table 5. Yearly medical interventions for CAPD patients. An ANOVA test shows that the
decrease of spontaneous visits are significant (P < 0.0066).

Yearly medical actions per Year

Programmed visits
Spontaneous visits
Total number of visits
Days at the hospital

Diatelic
10.62.3
2.82.1
13.43.4
1114.5

Reference
11.02.3
5.32.7
16.32.4
20.536.1

Table 6. Comparison of the frequency of patients visits with respect to their death. A Wilcoxon
test shows that deceased patients have more predicted visits (P < 0.019).

Visits per Year

Programmed Visits
Spontaneous Visits

Deceased Patient
12.53.72
3.53.8

Surviving Patient
10.91.9
2.163.36

Therefore, we could say that the use of Diatelic contributes to a global

enhancement of the patients health level which amounts to a global diminution of the
need for consultations. Similarly, the length of treatments at the hospital per year,
regardless of the hospitalization reason, shows a diminution of 46% in the Diatelic
group; however the very large standard deviation in both groups implies this loss is not
significant. There are too many in-group variations.
The numerical evaluation of the health level of patients is difficult to achieve, since
it is not directly measurable. However, we compared the evolution of three interesting
values: the weight, the average blood pressure, and the amount of drugs a patient uses
to regulate their blood pressure. Table 7 summarizes all these values, along with their
standard deviations. The first point of interest is that the weight increase of the patients
seems better controlled in the Diatelic group; however, the in-group deviations are so
large that this variation is not significant. Blood pressure shows a significant
(p < 0.03%) drop in the Diatelic group with respect to the Reference group. This is
even more important if we consider the raw values of the blood pressure presented in
Table 8. With these data, we can note that patients were globally in a hypertension
situation in both groups at the beginning of the experiment. After two years, the
Diatelic group returned to normal blood pressure values. Correlated with the weight
evolution and the almost significant (P < 0.0614%) drug consumption decrease, it
seems probable that these evolutions are due to a better hydration regulation.
Finally, the last objective of the Diatelic Project was to reduce the treatment costs
of CAPD patients, so that it could be applied to large populations. The trouble is that
these costs are difficult to evaluate. Actually, they include costs for treatments
(equipment, drugs and dialysis bags), hospitalizations, and transports. Since the
average distance from patients home to the ALTIR is statistically comparable in both
groups, our first costs estimates are strongly correlated to visits evolution and bring no
new information.
However, the ARH (Regional hospitalization agency) and the URCAM (Regional
union of medical insurance funds) are very interested in this system; they funded an
experiment extension for three more years and 150 patients. Therefore, Lorraine will
become a pilot site for evaluating the Diatelic system on a regional scale. The

AUTOMATED MEDICAL DIAGNOSIS WITH FUZZY STOCHASTIC MODELS

309

objective will be to cross-check the prospective studys conclusions and to evaluate

the impact of the equipment on a whole region on the medical costs of dialysis. In fact,
renal insufficiency is a public sanitary problem since 6,000 new patients are to be
treated in France every year. This amounts to 2% of the global cost of the French
sanitary system.
Table 7. Global evolution of medical signals over a two year period.

Variations of
Weight
Blood Pressure
Drugs

Diatelic
+0.413kg (4.3kg)
-1.177mm Hg (1.133mm Hg)
-0.2 (0.561)

Reference
+2.631kg (3.9kg)
-0.023mm Hg (1.582mm Hg)
+0.333 (0.9)

Table 8. Blood Pressure evolution over a two year period.

Blood Pressures (mm Hg)

Initial Systolic
Initial Diastolic
Final Systolic
Final Diastolic

Diatelic
13.731.6
7.871.2
11.531.6
7.11.1

Reference
13.332
81.1
13.91.5
7.90.8

6. CONCLUSION AND PERSPECTIVES

This article describes diagnosing software architecture which enables a simple
interaction with human specialists while maintaining a low computing complexity. We
ensured this intuitive interaction process by enforcing very strong medical semantics
in every part of the model. This way, without requiring special abilities in computer
science, it allows physicians to understand the actual influence of each model
parameter with respect to the diagnosis.
The low computing complexity is the consequence of the use of a classical
Partially Observable Markov Decision Process. This model combines a strong
mathematical background which makes coping with uncertainty and noise with proven
results possible, and very efficient algorithms like the Forward-Backward procedure
which makes computing of the patient diagnosis in real time possible.
We tested this system through a prospective randomized study in which 30 patients
were monitored for two years. The analysis of several parameters from the Diatelic
group, and their comparison with the Reference group suggests that our system was
beneficent to the patients health. From an economical point of view, this better health
condition implies fewer consultations and a large drop in the related costs. From a
medical point of view, patients seem to control their hydration-level better while
consuming fewer drugs. Several other parameters, like the hospitalization duration,
show an interesting influence, but the gathered data show too much in-group
variations to permit statistically significant conclusions.
This experiment has been elected to a duration extension by French sanitary
associations which offered financing for a three-year study on a regional scale: 150
patients will be monitored from several medical centres in Lorraine. To ensure the best
quality of services, a new enterprise has been funded: Diatelic S.A. which will ensure

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the installation and the maintenance of the computer systems at the patients home as
well as on the server side. It will also ensure software maintenance as well as
extensions and upgrades. Additionally, several dialysis centres in France, are starting
and using the system for their own patients monitoring.
There are several perspectives for enhancing the data analysis. We think the most
promising would regard continuous aspects. In particular, two particular points seem
important: smoothing the diagnosis and isolating proper actions to model. The
diagnosis may be smoothed by working from stereotyped situations to progressive
ones: currently, a given patient may be totally hyperhydrated, without any problem or
completely dehydrated. States probabilities should not be interpreted as intermediate
situations. For example, a patient who is diagnosed as 50% healthy and 50%
dehydrated is not really half-dehydrated. In fact, he may be totally dehydrated or
healthy, but the system is unable to decide. Using a state space that gradually evolves
from a healthy to a dehydrated condition would be more accurate. Moreover, the
patient dynamics could be better modelled with such a continuous state space since the
system would know how much a patient is dehydrated. Obviously, strong dehydration
is longer to heal than a light one.
The second major improvement would be to integrate dialysis options as actions in
the model. It seems obvious that it will be impossible to define more than one hundred
actions for each patient. To cope with this situation, we think we could use continuous
parametric actions. The idea is that the modelled phenomenon is physical; with few
parameters, we may be able to express the water amount a given bag will drain with
respect to the stasis duration. From this point, computing the right transition matrix
should be easy.
As a long-term improvement, we could imagine a system that would check the
appropriateness of the patients treatment, and propose modifications when useful.
This behaviour would be based on the planning functions of the POMDP. The trouble
is that these functions are very complex and computing intensive. The addition of
continuous elements would even worsen this situation. This is why we consider this
possibility for long term evolutions only.

ACKNOWLEDGMENTS
We would like to particularly thank Doctor Pierre-Yves Durand and
Professor Jacques Chanliau for their invaluable collaboration. From the ALTIR, they
tried and commented on several versions of the Diatelic system. Their feedback
contributed to most enhancements we have incorporated. Without their help, the
project certainly would not have achieved such results.

REFERENCES
Bellazzi, R. and P. Magni (2001). Improving dialysis services through Information Technology:
from telemedicine to data mining. Medinfo.
Bellot, D., J.P. Thomesse, A. Boyer, E. Campo, M. Chan, F. Charpillet, J. Fayn, C. Leschi,
N. Noury, V. Rialle, L. Romary, P. Rubel, N. Selmaoui, F. Steenkeste and G. Virone (2001).
Integrated Information Technologies for patients remote follow-up and homecare.
Healthcom.
Buchanan, B.G. and D.O. Duda (1982). Principles of Rule-Based Systems. Technical report
TR-82-926. Department of Computer Science, Stanford University.

AUTOMATED MEDICAL DIAGNOSIS WITH FUZZY STOCHASTIC MODELS

311

Buchanan, B.G. and E.H. Shortliffe (1984) Rule-Based Expert Systems, The MYCIN
Experiments of the Stanford Heuristic Programming Project. Addison-Wesley, Reading,
MA.
Chanliau, J., P.Y. Durand, M. Kessler, L. Romary, J.P. Thomesse, F. Charpillet, R. Hervy
(2000). DIATELIC: a new intelligent telemedicine system to avoid hydration disorders in
CAPD patients. Peritoneal Dialysis International 20 (Suppl 1): S77.
Charlson, M.E., P. Pompei, K.L. Ales and C.R. MacKenzie (1987). A new method of
classifying prognostic comorbidity in longitudinal studies: Development and validation.
Journal of Chronic Disease 40: 373-383
Chen, Z., D. Feng and X. Yu (2001). A Telemedicine System over Internet. In: Eades, Peter
and Jesse Jin (Eds). Selected papers from Pan-Sydney Workshop on Visual Information
Processing, Conferences in Research and Practice in Information Technology. Australian
Computer Society, Sydney.
Chen, H-T., W-C. Ma and D-M Liou (2002a). Design and Implementation of a Real-Time
Clinical Alerting System for Intensive Care Unit. American Medical Informatics
Association Annual Symposium.
Chen, D.R., W.J. Kuo, R.F. Chang, W.K. Moon and J.H. Lee (2002b). Computer-aided
diagnosis of breast tumors with different US systems. Academic Radiology 9: 793-799.
Forney, G.D. (1997). The forward-backward algorithm. Allerton conference on communication,
control and computing: 432-446.
Groselj, C. and M. Kukar (1999). Machine learning in stepwise diagnostic process. Joint
European Conference on Artificial Intelligence in Medicine and Medical Decision Making,
Aalborg, Denmark. pp. 315-325.
Horn W. (2001). AI in medecine on its way from knowledge-intensive to data-intensive
systems. Artificial Intelligence in Medicine: 23: 5-12.
Huang, C. (1999). Intelligent alarms: allocating attention among concurrent processes. PhD
Thesis, Stanford University.
Jeanpierre, L. (2002). Apprentissage et Adaptation pour la Modlisation Stochastique de
Systmes Dynamiques Rels. PhD thesis, Universit Henri Poincar Nancy-1, France.
Keravnou, E., N. Lavrac and B. Zupan (2000). Intelligent Data Analysis in Medicine.
Encyclopedia of Computer Science and Technology 42: 113-157.
Koenig, S. and R.G. Simmons (1996). Unsupervised learning of probabilistic models for robot
navigation. International Conference on Robotics and Automation, Minneapolis.
Kosh, A. and R. Slota (1999). PARMED-Information system for long distance collaboration in
medicine. Software for Communication Technologies, Linz.
Puterman, M. (1994). Markov Decision Processes: discrete stochastic dynamic programming.
John Wiley & Sons, New York.
Shortliffe, E.H. (1998). The evolution of health-care records in the era of the Internet. In: Cesnik
et al. (Eds). Medinfo 98. IOS Press, Amsterdam.
Steinmann, F. (2001). On the usefulness of fuzzy sets in medical AI. Artificial Intelligence in
Medicine 21: 131-137.