Zierk, Jakob ORCID: 0000-0002-9054-9544, Arzideh, Farhad, Kapsner, Lorenz A. ORCID: 0000-0003-1866-860X, Prokosch, Hans-Ulrich, Metzler, Markus and Rauh, Manfred (2020). Reference Interval Estimation from Mixed Distributions using Truncation Points and the Kolmogorov-Smirnov Distance (kosmic). Sci Rep, 10 (1). LONDON: NATURE PUBLISHING GROUP. ISSN 2045-2322

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Abstract

Appropriate reference intervals are essential when using laboratory test results to guide medical decisions. Conventional approaches for the establishment of reference intervals rely on large samples from healthy and homogenous reference populations. However, this approach is associated with substantial financial and logistic challenges, subject to ethical restrictions in children, and limited in older individuals due to the high prevalence of chronic morbidities and medication. We implemented an indirect method for reference interval estimation, which uses mixed physiological and abnormal test results from clinical information systems, to overcome these restrictions. The algorithm minimizes the difference between an estimated parametrical distribution and a truncated part of the observed distribution, specifically, the Kolmogorov-Smirnov-distance between a hypothetical Gaussian distribution and the observed distribution of test results after Box-Cox-transformation. Simulations of common laboratory tests with increasing proportions of abnormal test results show reliable reference interval estimations even in challenging simulation scenarios, when <20% test results are abnormal. Additionally, reference intervals generated using samples from a university hospital's laboratory information system, with a gradually increasing proportion of abnormal test results remained stable, even if samples from units with a substantial prevalence of pathologies were included. A high-performance open-source C++ implementation is available at https://gitlab.miracum.org/kosmic.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Zierk, JakobUNSPECIFIEDorcid.org/0000-0002-9054-9544UNSPECIFIED
Arzideh, FarhadUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kapsner, Lorenz A.UNSPECIFIEDorcid.org/0000-0003-1866-860XUNSPECIFIED
Prokosch, Hans-UlrichUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Metzler, MarkusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rauh, ManfredUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-345558
DOI: 10.1038/s41598-020-58749-2
Journal or Publication Title: Sci Rep
Volume: 10
Number: 1
Date: 2020
Publisher: NATURE PUBLISHING GROUP
Place of Publication: LONDON
ISSN: 2045-2322
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
PEDIATRIC REFERENCE INTERVALS; DETERMINING REFERENCE LIMITS; LABORATORY DATA-BASESMultiple languages
Multidisciplinary SciencesMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/34555

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