Table 1. Comparison of laboratory investigations using the
conventional approach and the LAS (Clin Chem 45:8 1168-1175
(1999)
Conventional
LAS
32.7
t = 5.4, P <0.01
7.5
t = 3.4, P <0.02
17.8
$232
t = 3.3, P <0.05
3.2
66%
12
$194
1.7
12
1.7
8
No established guidelines: hepatitis and autoimmune testing
Mean number of tests ordered
6.7
Total number of sample collections
38
3.3
30
Results returned negative
Mean number of tests ordered
Total number of sample collections
2
9
Results
Mean number of tests ordered
t-Test for two related samples
Mean number of samples collected
t-Test for two related samples
Observations
Mean costs, $
t-Test for two related samples
Turnaround time (mean no. of days)
Diagnostic accuracy
Number of referrals
Established guidelines: thyroid testing
Mean number of tests ordered
Total number of sample collections
4.8
14
5.8
1
100%
0
Enter Data
Generate Rule
Search Rule List
NEW RULE
Enter new Comment
RULE EXISTS
Search comment List
Update rule list
Retrieve Comment
Update comment list
Modify if required
Search Rule List
Variables Used
TFT application
• Qualitative
– Gender
– Clinical details
– Drug therapy
• Quantitative
–
–
–
–
–
Age
Total T4
TSH
Free T4
Free T3
Adult decision ranges
TSH (mu/L)
• Decision Range
–
–
–
–
–
–
–
–
>=60
>=20; <60
>=10; <20
>5; <10
>4; <=5
>=0.4; <4
>=0.25; <0.4
<0.25
• Description
–
–
–
–
–
–
–
–
Markedly high
Very High
High
Mildly raised
Near URL
Normal
Near LRL
Below detection limit
Clinical and Drug details
TFT
• CLINICAL DETAILS
– A. Suspected
hyperthyroidism
– B. Suspected
hypothyroidism
– C.Post Radioiodine therapy
– D. Post thyroid surgery
– E. On thyroxine treatment
– F. On T3 treatment
– G. On Carbimazole
– H. On PTU
– Z. Non-specific
• DRUG THERAPY
–
–
–
–
–
–
–
–
A. Lithium
B. Oestrogens
C. Amiodarone
D. Beta-blockers
E. Glucocorticoids
F. Phenytoin
G. Carbamazepine
H. Androgens
– Z. No relevant drugs
Variables Used
Protein electrophoresis
• Quantitative
– patients age
– serum total protein, albumin, -globulin, paraprotein
concentrations
• Semi-quantitative
– Visual assessment of albumin, 1,,2,, 1,,,,2,, and  concentrations
• Qualitative
– patients gender
– Visual inspection of zones and interzones (11 variables), e.g. 1
zone, - interzone findings
Primer knowledge bases
TFT application
Name
N1
N6
N15
N16
Etc…
TOTAL
Cases
44
44
143
143
1142
Case Types
Euthyroid
Euthyroid (post RAI)
Suppressed TSH
(thyrotoxicosis)
High TSH
(Hypothyroid)
Primer knowledge bases
protein electrophoresis
Name
S1
S2
S3
S4
Etc…
TOTAL
Cases
6
18
32
34
206
Case Types
Normal patterns
Chronic inflammation
patterns
Beat-gamma fusion
Altered alb/globulin fractions
Performance evaluation - TFT
Percentage AAI* per batch
Percentage of automatically assigned interpretations (AAI) per TFT batch
100
90
80
70
60
Consecutive TFT batches
TFT application statistics
•
•
•
•
•
•
Number of variables specified: 8
Number of options/decision levels: 70
Number of theoretical data combinations: 20,412,000
Number of cases entered via primer knowledge bases: 1142
Number of rules: >2900
Percentage of automatically assigned interpretations [using the primer
knowledge bases]
– At the outset: 66%
– After the first 500 patient cases: 70%
– Maximum achieved: 95%
• Number of interpretations rejected: <1%
electrophoresis application
statistics
•
•
•
•
•
•
Number of variables specified: 23 (22 used in rule generation)
Number of options/decision levels: 183
Number of theoretical data combinations: 8,800,000,000,000,000,000
Number of cases entered via primer knowledge bases: 206
Number of rules: 350
Percentage of automatically assigned interpretations [using the primer
knowledge bases]
– At the outset: 78%
– After the first 500 patient cases: 72%
– Maximum achieved: 70-80%
• Number of interpretations rejected: 0
Clinical evaluation
TFT application
(27 TFT requests on 15 randomly-selected new referrals to a thyroid clinic
were studied; 2 evaluators participated)
Do you agree with the
thyrometabolic classification in the
report?
 Complete agreement
 Partial agreement
 Complete disagreement
Evaluator 1
(physician)
Evaluator 2
(biochemist)
96%
4%
0%
85%
11%
4%
Was the interpretation clear in style 81%
and presentation?
96%
Were any references in the
interpretation to the following
items appropriate?
 Specific thyroid diagnoses [5]
 Interfering conditions/drugs [4]
 Further tests on the sample [1]
 Followup recommendations [16]
 Treatment recommendations [2]
Actual no. of
‘No’ answers
Actual no. of
‘No’ answers
0
4
0
0
0
1
0
1
1
0
Clinical evaluation
Electrophoresis application
(115 questionnaires circulated, 64 returned, 56% response)
Question
Answer - YES
Answer - NO
1. Did you require an
interpretation?
79%
21%
95%
5%
2. Was the interpretation helpful?
3. Did the interpretation confirm an
existing or suspected diagnosis? 24%
4. Did the interpretation lead to a
new diagnosis not previously
suspected?
0%
5. Did you perform further
investigations on the basis of the 14%
interpretation?
76%
100%
86%
Clinical evaluation
Electrophoresis application
(115 questionnaires circulated, 64 returned, 56% response)
Question
Answer - YES
Answer - NO
1. Did you require an
interpretation?
79%
21%
95%
5%
2. Was the interpretation helpful?
3. Did the interpretation confirm an
existing or suspected diagnosis? 24%
4. Did the interpretation lead to a
new diagnosis not previously
suspected?
0%
5. Did you perform further
investigations on the basis of the 14%
interpretation?
76%
100%
86%
Performance evaluation
Electrophoresis application
% AAI per batch of 100
cases
80
60
Without primer
With primer
40
20
0
100
200
300
400
500
Total Number of reports entered
Performance evaluation
Electrophoresis application
(to demonstrate knowledge acquisition)
% AAI per batch of 100
cases
80
60
All reports
labelled reports
40
20
0
100
200
300
400
500
Total Number of reports entered
Cooperativity
DATA
KBS
Interpretation
Diagnostic outcome
Cooperativity
KBS-1
KBS-2
KBS-3
KBS-4
Diagnostic outcome (1)
KBS-i
Comment
Diagnostic outcome (2)
Comment
Diagnostic outcome (3)
Comment
Diagnostic outcome (4)
Comment
Integrating
Comment
Cooperativity
Organ-related profiles
• Renal profile
– Na, K, Urea, Creatinine
• Bone profile
– Ca, Alb, Corr Ca, Phosphate, AlkPhos
• Liver profile
– Bili, Alb, T Protein, AST, Alk Phos, GGT
• Cardiac profile
• Lipid profile
Cooperativity
Decision Levels
160 mmol/L
Plasma
Sodium
Concentration
150 mmol/L
140 mmol/L
130 mmol/L
120 mmol/L
110 mmol/L
Rule Elements
Rules and rule elements
Diagnostic outcomes
Comments
R
Tr
L
Tl
B
Tb
C
Tc
Integrating rule and its elements
i
Age
Sex
Clin
Ti
Cooperativity
Primer knowledge bases
Universe KBS (Primers are subsets)
PRIMER
PRIMER
PRIMER
PRIMER
Renal
KBS
Bone
KBS
Liver
KBS
Cardiac/
Lipid
KBS
Selected Diagnostic Outcomes
• Renal profile
–
–
–
–
–
–
–
prerenal impairment
Renal impairment
hyponatraemia
hypokalaemia
hypernatraemia
hyperkalaemia
etc
• Bone profile
– osteomalacia pattern
– renal osteomalacia
– primary
hyperparathyroidism
– etc
Profile interpretations
• Renal
–
–
–
–
Na 133 [Low]
K 5.8 [Raised]
Urea 30.5 [raised]
Creatinine 400 [Raised]
• Interpretation
– Renal impairment with
hyperkalaemia and mild
hyponatraemia
• Diagnostic outcome
– renal impairment
• Bone
–
–
–
–
Ca 1.94 Corr Ca 2.04 [Low]
Alb 35 [Normal]
Phosphate 1.88 [High]
Alk Phos 450 [High]
• Interpretation
– Hypocalcaemia, raised
phosphate and Alk Phos:
osteomalacia pattern
• Diagnostic outcome
– osteomalacia pattern
Cooperative KBS output
• Renal KBS comment
– Renal impairment with hyperkalaemia and mild hyponatraemia.
[DO= renal impairment]
• Bone KBS comment
– hypocalcaemia, raised phosphate and Alk Phos. DO =
osteomalacia pattern.
• Integrating KBS comment
– These results are consistent with renal failure and associated renal
osteodystrophy
Decision Support Systems
Support for Health Care Professionals
Alarm/Alert Systems
Alert
A significant but mild trend in a variable, or the
achievement of a specified level by the variable.
Univariate Alerts: based on a single variable
Multivariate Alerts: based on multiple variables
Alarm
A marked trend in single variable, or the achievement
of a critical specified level by the variable, and/or the
presence of several (multiple) alerts or multivariate
alerts.
Univariate Alarms: based on a single variable
Multivariate Alarms: based on multiples
variables
Alarm/Alert Systems
Methods
 Alarms/alerts based on Critical Values
 Alerts/alarms based on Critical Trends
 Mathematical/Statistical methods
 Biodynamic Models
 KBS/Temporal reasoning systems
 Know ledge-based (intelligent) alerts/alarms
 Cooperative systems
Alarm/Alert Systems
Based on
Significant
Values
Based on
Significant
Trends
Univariate Alerts
If Sodium_Concentration <125 mmol/l
Then
Set Alert [Sodium_Concentration] ON;
End;
If Potassium_Trend >0.1 mmol/l/hr
Then
Set Alert [K_Trend] ON
End;
Alarm/Alert Systems
Based on
Significant
Values
Multivariate Alerts
If
Sodium< 125
and Water_Balance > 1000ml
and Urea NOT RAISED
Then Set Alert [Dilution_Hyponatraemia] ON
End;
Based on
Significant
Trends
If
Potassium_Trend > 0.1 mmol/l/hr
and K_Infusion > 5 mmol/hr
and Potassium_Concentration> 4.5 mmol/l
Then
Set Alert [Hyperkalaemia_ trend] ON
End;
Know ledgebased alerts
If
and
and
and
and
and
Then
End;
Sodium< 125 mmol/l
Urine Osmolality > 350 mosm/kg
cvp NORMAL
Urea NOT RAISED
Euthyroid/EuAdrenal
CARBAMAZEPINE Therapy
Set Alerts [SIADH]; [CBZ effect] ON
Alarm/Alert Systems
Calibration
Alarms, when triggered, should lead to an immediate change in
patient care.
Alarms which do not lead to a change in patient care (false alarms)
should be suppressed on subsequent occasions, or converted to an
alert status.
Suppression could also be achieved by knowledge-based revision of
the Trigger Thresholds.
Repeated alarms may be ignored.
Alarms need to be responsive to the clinical context
Alarms should draw attention to new or strange findings.
Alarm/Alert Systems
Based on Significant
Values
Based on Significant
Trends
Univariate Alarms
If Sodium_Concentration <120 mmol/l Then
Set Alarm [Hyponatraemia] ON;
End;
If Potassium_Trend >0.5 mmol/l/hr Then
Set Alarm [K_Trend] ON
End;
Alarm/Alert Systems
Based on Significant
Values
Based on Significant
Trends
Multivariate Alarms
If
Sodium<120
and
Water_Balance > 1000ml
and
Urea NOT RAISED
Then
Set Alarm [Dilution_Hyponatraemia] ON
End;
If
and
and
Then
Potassium_Trend >0.5 mmol/l/hr
K_Infusion > 5 mmol/hr
Potassium_Concentration>5.0 mmol/l
Set Alarm [Hyperkalaemia_ trend] ON
End;
Knowledge-based
alarms
If
and
and
and
Then
End;
Sodium<115
Alert [SIADH] ON
Alert [Sodium_Trend] POSITIVE
Alert [Hyponatraemia] ON
Suppress Alarm [Hyponatraemia]
Alarm/Alert Systems
Variables specified in the Alarms/Alerts System.
Test*
Type**
Categories***
Renal Sub-system:
Sodium (mmol/l)
Potassium (mmol/l)
Urea (mmol/l)
Creatinine (mol/l)
Bicarbonate (mmol/l)
Chloride (mmol/l)
Glucose (mmol/l)
QN
QN
QN
QN
QN
QN
QN
20
20
20
20
20
5
8
Acid-Base Sub-system:
Arterial blood pH
Arterial blood pCO2
Arterial blood pO2
QN
QN
QN
5
5
9
Haemodynamic Sub-system:
Central venous pressure (mmHg)
Cardiac failure index
Oedema index
Temperature index
Pulse rate
Blood pressure index
Weight change
Urine Output
Sodium balance (mmol/day)
Sodium output (mmol/day)
Potassium balance (mmol/day)
Potassium output (mmol/day)
Nitrogen balance (g/day)
Nitrogen output (g/day)
Water balance (litres/day)
QN
QL
QL
QL
QN
QL
QN
QN
QN
QN
QN
QN
QN
QN
QN
4
2
2
3
5
3
5
6
6
5
4
4
6
5
6
Footnote: *All laboratory tests are plasma concentrations or activities unless stated otherwise. **Each test is classified as
quantitative (QN) or qualitative (QL). ***The number of decision levels specified is given for quantitative variables and the
number of options specified for qualitative variables.
Alarm/Alert Systems
Variables specified in the Alarms/Alerts System.
Test*
Type**
Categories***
Critical Care Chemistry Sub-system:
Bilirubin (mol/l)
Blood prothrombin time
Albumin (g/l)
Total protein (g/l)
Aspartate aminotransferase (u/l)
Amylase (u/l)
Calcium (mmol/l)
Phosphate (mmol/l)
Creatine kinase (u/l)
Alkaline phosphatase (u/l)
Alanine aminotransferase (u/l)
Gamma-glutamyl transferase (u/l)
Urate (mmol/l)
Triglyceride (mmol/l)
Blood haemoglobin concentration
Blood white cell count
Magnesium (mmol/l)
QN
QN
QN
QN
QN
QN
QN
QN
QN
QN
QN
QN
QN
QN
QN
QN
QN
15
5
14
13
15
5
20
19
15
17
15
15
4
18
8
7
6
Variables considered at the Integrating System level:
Renal Diagnostic Outcome
Acid-Base Diagnostic Outcome
Haemodynamic Diagnostic Outcome
Critical Care Chemistry Diagnostic Outcome
QL
QL
QL
QL
Coded
Coded
Coded
Coded
Variables available to all participating systems:
Age
Sex
Clinical information
QN
QL
QL
Adult, Child
M, F
Coded entries A-Z
entries
entries
entries
entries
000-099
000-099
000-099
000-099
Footnote: *All laboratory tests are plasma concentrations or activities unless stated otherwise. **Each test is classified as
quantitative (QN) or qualitative (QL). ***The number of decision levels specified is given for quantitative variables and the
number of options specified for qualitative variables.
Alarm/Alert Systems
Example of output of the alarms/alerts System.

60 year old male with pyrexia (39 Celsius)
PlasmaSodium
Potassium
Urea
Creatinine
152
3.9
4.5
98
Diagnostic Outcomes
Renal DSS:
Acid-Base DSS:
Haemodynamic DSS:
Univariate Alert: Moderate hypernatraemia.
No Results.
Univariate Alert: Pyrexia
Critical Care Chemistry DSS:
Integrating Interpretation
Integrating KBS:
mmol/l[135-145]
mmol/l[3.5-5.0]
mmol/l[3.0-7.0]
mol/l [60-100]
No Results.
Multivariate Alert: Dehydration in a pyrexial
patient.
Decision Support Systems
Support for Health Care Professionals
• Microbiology Applications
– Computerised infectious disease monitor (Evans, 1986).
Computer-generated alarms were produced for (1) all patients with
hospital-acquired infections; (2) patients on antibiotics to which
they were not susceptible; (3) who could be receiving less
expensive antibiotics; (4) who were receiving prophylactic
antibiotcis for too long. Use of the system saved time for hospital
infection control staff, and improved antibiotic use.
– MRSA monitor (Safran, Scherrer 1994). Infection control nurses
were provided daily with computer-generated lab alerts giving
details of MRSA+ together with re-admission alerts giving details
of new admissions previously known to be colonised with MRSA.
System saved time for ICNs and helped as a preventive warning.
Decision Support Systems
Support for Health Care Professionals
• Histopathology/Cytopathology applications
– PAPNET Cervical Screening Neural Network
– Telepathology
Decision Support Systems
Support for Health Care Professionals
• Haematology applications
– Diamond and Nguyen/Coulter Electronics.
Various DSS applications for use with Coulter
systems, flow cytometry, classification of
haematological malignancies etc.
EQA Applications
• EQA Toolkit