Veli Kairisto
22.11.1995
University of Turku / Medical
Faculty / Dept. of Clinical
Chemistry
Annales Universitatis Turkuensis D203, 128 pages, 1995
Distributor of the Thesis: Turku University Library, FIN-20500 Turku, Finland
(fax: +358-21-3335050)
Abstract
List
of original communications
Supervisors,
reviewers and the opponent
Abstract
Availability of reference values is the basic requirement for the clinical
use of laboratory tests. Reference values produced from patients correspond
closely to the needs of clinical test interpretation provided that the
patients are reliably grouped into different diagnostic categories. Hospital
database information has previously been used mainly for epidemiologic
and administrative purposes and it has not been customary to use the data
in patient care. This study was undertaken to study the possibilities of
using routinely available computerized patient data for the production
of reference values.
In the different parts of the study reference values were produced from
patient data for the diagnosis of pheochromocytoma, for the diagnosis of
myocardial damage, for the characterization of usual red blood cell values
in hospitalized patients, and for the detection of random analytical or
preanalytical errors in a multichannel hematology analyzer. By the used
methods it was possible to obtain representative and large reference sample
groups, which facilitated, for example, the observation of previously unreported
significant dependencies of urinary normetanephrine excretion, and serum
LD-1 and CK-MB activities on age.
Red blood cell values can be affected by several different diseases and
treatments. A set of exclusion criteria based on hospital discharge diagnoses
was developed. In the construction of quality control limits for the detection
of random errors in a multichannel hematology analyzer it was not necessary
to remove the illness-related values, on the contrary, those were considered
necessary for the correct estimation of the quality control limits. Physiological
interdependence of the red blood cell values was utilized for the detection
of aberrant results. Using reference data obtained from the patients a
bivariate reference region was constructed for the detection of most unusual
combinations of results and possible random errors.
In the detection of myocardial damage, quite as in several other clinical
uses of laboratory tests, it is important to observe not only single test
results but also the changes between consecutively collected samples. Using
the cardiac enzyme data as a model a new indirect method was developed
for the estimation of reference change limits from routine patient data.
Previously indirect methods have not been used for the estimation of reference
changes. The proposed algorithm was included in the software developed
during the study.
The availability of several sets of reference values
produced from patient databases would make it increasingly important to
understand and use properly such concepts as decision limit, clinical sensitivity
and clinical specificity, predictive values, and ROC-curves. In the second
part of the study a computer program with graphical user interface was
constructed. Illustrative display of reference distributions forms the
core of the software. Numerical data is not shown unless requested. Relevant
numbers can be "picked up" from the graph by simple mouse operations.
The program includes several previously published methods for the treatment
of reference values. The optimization of bin widths for illustrative graphical
presentation of reference distributions and ROC-curves and the indirect
method for the estimation of health-related change limits are previously
unpublished features developed during this study.
As a summary of this study it can be concluded that hospital databases
can be used for the production of clinically useful reference values. However,
the possibilities for reference value production are in some cases still
severely limited due to insufficiencies in the computerized source data.
Knowledge about this should encourage physicians to improve the contents
of the databases further. Improved accuracy in the classification of hospitalized
reference patients would benefit the clinical use of laboratory tests and
the diagnostic process.
The thesis was based on the following papers:
Associate Professor Veikko Näntö
M.D., Department of Clinical Chemistry, University of Turku
and
Associate Professor Esa Uusipaikka
Ph.D., Department of Statistics, University of Turku
Associate Professor Aimo Ruokonen
M.D., Department of Clinical Chemist,y, University of Oulu
and
Consultant Per Winkel
M.D., Department of Clinical Biochemistry, University of Copenhagen
Professor Ralph Gräsbeck
M.D., Department of Medical Biochemistry, University of Kuwait
and Department of Clinical Chemistry, University of Helsinki