High-resolution pediatric reference intervals for 15 biochemical analytes described using fractional polynomials

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Jakob Zierk ◽  
Hannsjörg Baum ◽  
Alexander Bertram ◽  
Martin Boeker ◽  
Armin Buchwald ◽  
...  
Keyword(s):  
Information Systems ◽  
Laboratory Test ◽  
Clinical Decision Making ◽  
Age Groups ◽  
Clinical Decision ◽  
Reference Intervals ◽  
Test Results ◽  
Laboratory Test Results ◽  
Glutamyl Transferase ◽  
Laboratory Information Systems

Abstract Objectives Assessment of children’s laboratory test results requires consideration of the extensive changes that occur during physiological development and result in pronounced sex- and age-specific dynamics in many biochemical analytes. Pediatric reference intervals have to account for these dynamics, but ethical and practical challenges limit the availability of appropriate pediatric reference intervals that cover children from birth to adulthood. We have therefore initiated the multi-center data-driven PEDREF project (Next-Generation Pediatric Reference Intervals) to create pediatric reference intervals using data from laboratory information systems. Methods We analyzed laboratory test results from 638,683 patients (217,883–982,548 samples per analyte, a median of 603,745 test results per analyte, and 10,298,067 test results in total) performed during patient care in 13 German centers. Test results from children with repeat measurements were discarded, and we estimated the distribution of physiological test results using a validated statistical approach (kosmic). Results We report continuous pediatric reference intervals and percentile charts for alanine transaminase, aspartate transaminase, lactate dehydrogenase, alkaline phosphatase, γ-glutamyl-transferase, total protein, albumin, creatinine, urea, sodium, potassium, calcium, chloride, anorganic phosphate, and magnesium. Reference intervals are provided as tables and fractional polynomial functions (i.e., mathematical equations) that can be integrated into laboratory information systems. Additionally, Z-scores and percentiles enable the normalization of test results by age and sex to facilitate their interpretation across age groups. Conclusions The provided reference intervals and percentile charts enable precise assessment of laboratory test results in children from birth to adulthood. Our findings highlight the pronounced dynamics in many biochemical analytes in neonates, which require particular consideration in reference intervals to support clinical decision making most effectively.

scholarly journals Data mining of pediatric reference intervals

2021 ◽  
Vol 45 (6) ◽  
pp. 311-317
Author(s):  
Jakob Zierk ◽  
Markus Metzler ◽  
Manfred Rauh
Keyword(s):  
Data Mining ◽  
Information Systems ◽  
Statistical Methods ◽  
Clinical Decision Making ◽  
Reference Intervals ◽  
Healthy Children ◽  
Test Results ◽  
Young Infants ◽  
Age Related ◽  
Laboratory Test Results

Abstract Laboratory tests are essential to assess the health status and to guide patient care in individuals of all ages. The interpretation of quantitative test results requires availability of appropriate reference intervals, and reference intervals in children have to account for the extensive physiological dynamics with age in many biomarkers. Creation of reference intervals using conventional approaches requires the sampling of healthy individuals, which is opposed by ethical and practical considerations in children, due to the need for a large number of blood samples from healthy children of all ages, including neonates and young infants. This limits the availability and quality of pediatric reference intervals, and ultimately negatively impacts pediatric clinical decision-making. Data mining approaches use laboratory test results and clinical information from hospital information systems to create reference intervals. The extensive number of available test results from laboratory information systems and advanced statistical methods enable the creation of pediatric reference intervals with an unprecedented age-related accuracy for children of all ages. Ongoing developments regarding the availability and standardization of electronic medical records and of indirect statistical methods will further improve the benefit of data mining for pediatric reference intervals.

Pediatric reference interval verification for endocrine and fertility hormone assays on the Abbott Alinity system

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Mary Kathryn Bohn ◽  
Siobhan Wilson ◽  
Alexandra Hall ◽  
Khosrow Adeli
Keyword(s):  
Clinical Decision Making ◽  
De Novo ◽  
Reference Interval ◽  
Clinical Decision ◽  
Reference Intervals ◽  
Healthy Children ◽  
Confidence Limits ◽  
Test Results ◽  
Serum Samples ◽  
Abbott Architect

Abstract Objectives The Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) has developed an extensive database of reference intervals (RIs) for several biomarkers on various analytical systems. In this study, pediatric RIs were verified for key immunoassays on the Abbott Alinity system based on the analysis of healthy children samples and comparison to comprehensive RIs previously established for Abbott ARCHITECT assays. Methods Analytical performance of Alinity immunoassays was first assessed. Subsequently, 100 serum samples from healthy children recruited with informed consent were analyzed for 16 Alinity immunoassays. The percentage of test results falling within published CALIPER ARCHITECT reference and confidence limits was determined. If ≥ 90% of test results fell within the confidence limits, they were considered verified based on CLSI guidelines. If <90% of test results fell within the confidence limits, additional samples were analyzed and new Alinity RIs were established. Results Of the 16 immunoassays assessed, 13 met the criteria for verification with test results from ≥ 90% of healthy serum samples falling within the published ARCHITECT confidence limits. New CALIPER RIs were established for free thyroxine and prolactin on the Alinity system. Estradiol required special considerations in early life. Conclusions Our data demonstrate excellent concordance between ARCHITECT and Alinity immunoassays, as well as the robustness of previously established CALIPER RIs for most immunoassays, eliminating the need for de novo RI studies for most parameters. Availability of pediatric RIs for immunoassays on the Alinity system will assist clinical laboratories using this new platform and contribute to improved clinical decision-making.

scholarly journals Verification of reference intervals in routine clinical laboratories: practical challenges and recommendations

2018 ◽  
Vol 0 (0) ◽  
Author(s):  
Yesim Ozarda ◽  
Victoria Higgins ◽  
Khosrow Adeli
Keyword(s):  
Clinical Laboratory ◽  
Local Population ◽  
Age Groups ◽  
External Source ◽  
Reference Intervals ◽  
Laboratory Method ◽  
Test Results ◽  
Multicenter Studies ◽  
Clinical Laboratories ◽  
Laboratory Test Results

Abstract Reference intervals (RIs) are fundamental tools used by healthcare and laboratory professionals to interpret patient laboratory test results, ideally enabling differentiation of healthy and unhealthy individuals. Under optimal conditions, a laboratory should perform its own RI study to establish RIs specific for its method and local population. However, the process of developing RIs is often beyond the capabilities of an individual laboratory due to the complex, expensive and time-consuming process to develop them. Therefore, a laboratory can alternatively verify RIs established by an external source. Common RIs can be established by large, multicenter studies and can subsequently be received by local laboratories using various verification procedures. The standard approach to verify RIs recommended by the Clinical Laboratory Standards Institute (CLSI) EP28-A3c guideline for routine clinical laboratories is to collect and analyze a minimum of 20 samples from healthy subjects from the local population. Alternatively, “data mining” techniques using large amounts of patient test results can be used to verify RIs, considering both the laboratory method and local population. Although procedures for verifying RIs in the literature and guidelines are clear in theory, gaps remain for the implementation of these procedures in routine clinical laboratories. Pediatric and geriatric age-groups also continue to pose additional challenges in respect of acquiring and verifying RIs. In this article, we review the current guidelines/approaches and challenges to RI verification and provide a practical guide for routine implementation in clinical laboratories.

Age- and Sex-Specific Dynamics in 22 Hematologic and Biochemical Analytes from Birth to Adolescence

2015 ◽  
Vol 61 (7) ◽  
pp. 964-973 ◽  
Author(s):  
Jakob Zierk ◽  
Farhad Arzideh ◽  
Tobias Rechenauer ◽  
Rainer Haeckel ◽  
Wolfgang Rascher ◽  
...  
Keyword(s):  
Cell Count ◽  
Clinical Decision Making ◽  
Clinical Care ◽  
Age Groups ◽  
Reference Intervals ◽  
Interindividual Variation ◽  
Red Cell ◽  
Distribution Width ◽  
Laboratory Test Results ◽  
Age And Sex

Abstract BACKGROUND Pediatric laboratory test results must be interpreted in the context of interindividual variation and age- and sex-dependent dynamics. Reference intervals as presently defined for separate age groups can only approximate the age-related dynamics encountered in pediatrics. Continuous reference intervals from birth to adulthood are not available for most laboratory analytes because of the ethical and practical constraints of defining reference intervals using a population of healthy community children. We applied an indirect method to generate continuous reference intervals for 22 hematologic and biochemical analytes by analyzing clinical laboratory data from blood samples taken during clinical care of patients. METHODS We included samples from 32 000 different inpatients and outpatients (167 000 samples per analyte) from a German pediatric tertiary care center. Measurements were performed on a Sysmex-XE 2100 and a Cobas Integra 800 during clinical care over a 6-year period. The distribution of samples considered normal was estimated with an established indirect statistical approach and used for the calculation of reference intervals. RESULTS We provide continuous reference intervals from birth to adulthood for 9 hematology analytes (hemoglobin, hematocrit, red cell indices, red cell count, red cell distribution width, white cell count, and platelet count) and 13 biochemical analytes (sodium, chloride, potassium, calcium, magnesium, phosphate, creatinine, aspartate transaminase, alanine transaminase, γ-glutamyltransferase, alkaline phosphatase, lactate dehydrogenase, and total protein). CONCLUSIONS Continuous reference intervals capture the population changes in laboratory analytes during pediatric development more accurately than age groups. After local validation, the reference intervals provided should allow a more precise consideration of these dynamics in clinical decision making.

Establishment of Reference Intervals for Alkaline Phosphatase in Pakistani Children Using a Data Mining Approach

2019 ◽  
Vol 51 (5) ◽  
pp. 484-490 ◽  
Author(s):  
Sibtain Ahmed ◽  
Jakob Zierk ◽  
Aysha Habib Khan
Keyword(s):  
Data Mining ◽  
Alkaline Phosphatase ◽  
Clinical Decision Making ◽  
Clinical Chemistry ◽  
Age Groups ◽  
Clinical Decision ◽  
German Society ◽  
Reference Intervals ◽  
Photometric Method ◽  
Data Mining Approach

Abstract Objective To establish reference intervals (RIs) for alkaline phosphatase (ALP) levels in Pakistani children using an indirect data mining approach. Methods ALP levels analyzed on a Siemens Advia 1800 analyzer using the International Federation of Clinical Chemistry’s photometric method for both inpatients and outpatients aged 1 to 17 years between January 2013 and December 2017, including patients from intensive care units and specialty units, were retrieved. RIs were calculated using a previously validated indirect algorithm developed by the German Society of Clinical Chemistry and Laboratory Medicine’s Working Group on Guide Limits. Results From a total of 108,845 results, after the exclusion of patients with multiple specimens, RIs were calculated for 24,628 males and 18,083 females with stratification into fine-grained age groups. These RIs demonstrate the complex age- and sex-related ALP dynamics occurring during physiological development. Conclusion The population-specific RIs serve to allow an accurate understanding of the fluctuations in analyte activity with increasing age and to support clinical decision making.

Establishing and using reference intervals

2020 ◽  
Vol 45 (1) ◽  
pp. 1-10
Author(s):  
Yesim Ozarda
Keyword(s):  
Clinical Chemistry ◽  
Laboratory Data ◽  
Age Groups ◽  
Clinical Decision ◽  
Reference Population ◽  
External Source ◽  
Reference Intervals ◽  
Multicenter Studies ◽  
Indirect Methods ◽  
Laboratory Test Results

AbstractReference intervals (RIs) and clinical decision limits (CDLs) are fundamental tools used by healthcare and laboratory professionals to interpret patient laboratory test results. The traditional method for establishing RIs, known as the direct approach, is based on collecting samples from members of a preselected reference population, making the measurements and then determining the intervals. For challenging groups such as pediatric and geriatric age groups, indirect methods are appointed for the derivation of RIs in the EP28-A3c guideline. However, there has been an increasing demand to use the indirect methods of deriving RIs by the use of routine laboratory data stored in the laboratory information system. International Federation of Clinical Chemistry (IFCC), Committee on Reference Intervals and Decision Limits (C-RIDL) is currently working on the study for the comparison of the conventional (direct) and alternative (indirect) approaches for the determination of reference intervals. As a matter of fact that, the process of developing RIs is often beyond the capabilities of an individual laboratory due to the complex, expensive and time-consuming process to develop them. Therefore, a laboratory can alternatively transfer and verify RIs established by an external source (i.e. manufacturers’ package inserts, publications). IFCC, C-RIDL has focused primarily on RIs and has performed multicenter studies to obtain common RIs in recent years. However, as the broader responsibility of the Committee, from its name, includes “decision limits”, the C-RIDL also emphasizes the importance of the correct use of both RIs and CDLs and to encourage laboratories to specify the appropriate information to clinicians as needed.

scholarly journals Post-analytical laboratory work: national recommendations from the Working Group for Post-analytics on behalf of the Croatian Society of Medical Biochemistry and Laboratory Medicine

2019 ◽  
Vol 29 (2) ◽  
pp. 228-261 ◽  
Author(s):  
Jasna Lenicek Krleza ◽  
Lorena Honovic ◽  
Jelena Vlasic Tanaskovic ◽  
Sonja Podolar ◽  
Vladimira Rimac ◽  
...  
Keyword(s):  
Best Practices ◽  
Clinical Decision Making ◽  
Clinical Decision ◽  
Test Results ◽  
Final Phase ◽  
Timely Manner ◽  
Guidelines Implementation ◽  
Laboratory Test Results ◽  
Analytical Phase ◽  
Total Testing Process

The post-analytical phase is the final phase of the total testing process and involves evaluation of laboratory test results; release of test results in a timely manner to appropriate individuals, particularly critical results; and modification, annotation or revocation of results as necessary to support clinical decision-making. Here we present a series of recommendations for post-analytical best practices, tailored to medical biochemistry laboratories in Croatia, which are intended to ensure alignment with national and international norms and guidelines. Implementation of the national recommendations is illustrated through several examples.

Mining the Age-Dependent Reference Intervals of B Vitamins from Routine Laboratory Test Results

2018 ◽  
Vol 50 (1) ◽  
pp. 54-63 ◽  
Author(s):  
Osman Evliyaoglu ◽  
Josef van Helden ◽  
Matthias Imöhl ◽  
Ralf Weiskirchen
Keyword(s):  
Laboratory Test ◽  
Reference Intervals ◽  
B Vitamins ◽  
Routine Laboratory ◽  
Test Results ◽  
Routine Laboratory Test ◽  
Laboratory Test Results ◽  
Age Dependent

scholarly journals A New Biomedical Passage Retrieval Framework for Laboratory Medicine: Leveraging Domain-specific Ontology, Multilevel PRF, and Negation Differential Weighting

2018 ◽  
Vol 2018 ◽  
pp. 1-19
Author(s):  
Keejun Han ◽  
Hyoeun Shim ◽  
Mun Y. Yi
Keyword(s):  
Decision Making ◽  
Laboratory Test ◽  
Query Processing ◽  
Clinical Decision ◽  
Domain Ontology ◽  
Test Results ◽  
Passage Retrieval ◽  
Laboratory Test Results ◽  
Differential Weighting ◽  
Processing Engine

Clinical decision support (CDS) search is performed to retrieve key medical literature that can assist the practice of medical experts by offering appropriate medical information relevant to the medical case in hand. In this paper, we present a novel CDS search framework designed for passage retrieval from biomedical textbooks in order to support clinical decision-making using laboratory test results. The framework utilizes two unique characteristics of the textual reports derived from the test results, which are syntax variation and negation information. The proposed framework consists of three components: domain ontology, index repository, and query processing engine. We first created a domain ontology to resolve syntax variation by applying the ontology to detect medical concepts from the test results with language translation. We then preprocessed and performed indexing of biomedical textbooks recommended by clinicians for passage retrieval. We finally built the query-processing engine tailored for CDS, including translation, concept detection, query expansion, pseudo-relevance feedback at the local and global levels, and ranking with differential weighting of negation information. To evaluate the effectiveness of the proposed framework, we followed the standard information retrieval evaluation procedure. An evaluation dataset was created, including 28,581 textual reports for 30 laboratory test results and 56,228 passages from widely used biomedical textbooks, recommended by clinicians. Overall, our proposed passage retrieval framework, GPRF-NEG, outperforms the baseline by 36.2, 100.5, and 69.7 percent for MRR,R-precision, and Precision at 5, respectively. Our study results indicate that the proposed CDS search framework specifically designed for passage retrieval of biomedical literature represents a practically viable choice for clinicians as it supports their decision-making processes by providing relevant passages extracted from the sources that they prefer to refer to, with improved performances.

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