scholarly journals Establishing laboratory-specific reference intervals for TSH and fT4 by use of the indirect Hoffman method

PLoS ONE ◽  
2022 ◽  
Vol 17 (1) ◽  
pp. e0261715
Author(s):  
Sylwia Płaczkowska ◽  
Małgorzata Terpińska ◽  
Agnieszka Piwowar
Keyword(s):  
Low Cost ◽  
Adult Population ◽  
Age Groups ◽  
Large Data ◽  
Reference Intervals ◽  
Medical Laboratory ◽  
Specific Reference ◽  
Medical Decisions ◽  
Indirect Methods ◽  
Laboratory Information Systems

Background The results of examinations of laboratory parameters are the basis of appropriate medical decisions. The availability of reliable and accurate reference intervals (RIs) for each laboratory parameter is an integral part of its appropriate interpretation. Each medical laboratory should confirm their RIs. Up-to-date reference intervals for thyroid function hormones are still a matter of ongoing controversy. The aim of the study was the application of the indirect Hoffman method to determine RIs for TSH and fT4 based on the large data pools stored in laboratory information systems and the comparison of these RIs to generally used RIs. Material and methods The TSH and fT4 routine examination results of hospitalized and outpatient populations were collected over five years (2015–2019), and reference limits were established by the improved Hoffmann method after the exclusion of outliers. Comparative verification of established RIs was conducted with the RIs values provided by test manufacturers and literature data. Results Various RIs were observed in different age groups in the examined populations. For TSH, RIs varied between different age groups, with a narrower range of RIs in the studied adult population and a shift of both reference boundaries toward higher values in comparison to manufacturers’ data among children. RIs estimated for fT4 were very similar to the manufacturer and literature data. Conclusion Thyroid hormone levels change during a person’s lifetime and vary between sexes, but this difference does not always influence the clinical interpretation of laboratory results in the context of RIs. The use of indirect methods is justified due to the ease and low cost of their application.

scholarly journals Establishing Laboratory-Specific Reference Intervals for TSH and fT4 by use of the Indirect Hoffman Method

2021 ◽  
Author(s):  
Sylwia Płaczkowska ◽  
Małgorzata Terpińska ◽  
Agnieszka Piwowar
Keyword(s):  
Low Cost ◽  
Adult Population ◽  
Age Groups ◽  
Large Data ◽  
Reference Intervals ◽  
Medical Laboratory ◽  
Specific Reference ◽  
Medical Decisions ◽  
Indirect Methods ◽  
Laboratory Information Systems

Abstract Background: The results of examinations of laboratory parameters are the basis of appropriate medical decisions. The availability of reliable and accurate reference intervals (RIs) for each laboratory parameter is an integral part of its appropriate interpretation. Each medical laboratory should confirm their RIs. Up to date reference intervals for thyroid function hormones are still a matter of ongoing controversy. The aim of the study was application of the indirect Hoffman method to determine RIs for TSH and fT4 based on the large data pools stored in laboratory information systems, and the comparison of these RIs to generally used RIs.Material and methods: The TSH and fT4 routine examination results of a hospitalized and outpatients population over five years (2015-2019) were collected, and reference limits were established by the improved Hoffmann method after the exclusion of outliers. Comparative verification of established RIs was conducted with the RIs values provided by test manufacturers and literature data.Results: The various RIs in different age groups in examined populations were observed. For TSH RIs varied between different age groups, with a narrower range of RIs in the studied adult population, while for children, a shift of both reference boundaries toward higher values in comparison to manufacturers' data was observed. RIs estimated for fT4 were very similar to the manufacturer and literature data.Conclusion: Thyroid hormone levels change during a person's lifetime and vary between sexes, but this difference does not always influence the clinical interpretation of laboratory results in the context of RIs. The use of indirect methods is justified due to the ease and low cost of their application.

Age-Specific Reference Intervals for PT, aPTT, Fibrinogen and Thrombin Time for Parturient Women

2019 ◽  
Vol 119 (06) ◽  
pp. 894-898
Author(s):  
Gao-Ming Zhang ◽  
Wei Zhang ◽  
Guo-Ming Zhang
Keyword(s):  
Age Groups ◽  
Reference Intervals ◽  
Activated Partial Thromboplastin Time ◽  
Blood Levels ◽  
Specific Reference ◽  
Thrombin Time ◽  
Healthy Individuals ◽  
Medical Decisions ◽  
Large Dataset ◽  
Upper Limit

Background Parturient women are healthy individuals who require special consideration. Parturient women are considered to be in a hyper-coagulable state. For example, the fibrinogen (FIB) levels are often higher than the upper limit of normal reference intervals (RIs) in parturient women than in non-parturient healthy individuals (2–4 g/L). Objective The aim of this study is to establish the RIs of pro-thrombin time (PT), activated partial thromboplastin time (aPTT), FIB levels and thrombin time (TT) for parturient women. Materials and Methods Blood levels of PT, aPTT, FIB and TT were assayed on an ACL TOP 700 automatic coagulation analyser using plasma samples from 10,472 parturient women. Outlier results were excluded by using Tukey's test. The RIs were calculated by the Clinical and Laboratory Standards Institute C28-A3 guideline. Results The RIs of PT, aPTT, FIB and TT were 8.7 to 12.1 seconds (8.7–12.2 seconds for 16–20 years old, 8.7–12.1 second for 21–25 years old, 8.6–12.0 second for 26–30 years old, 8.7–12.0 second for 31–35 years old, 8.7–12.6 second for 36–40 years old and 8.8–12.2 second for 41 years old), 22.9 to 42.3 seconds, 1.98 to 5.82 g/L and 9.9 to 16.7 seconds, respectively. PT levels were found to be positively associated with aging. Conclusion The above-established age-specific RIs, defined by using a large dataset, may assist clinicians in making accurate medical decisions. This was the first study in which the RIs of PT, aPTT, FIB and TT were established for parturient women in different age groups.

scholarly journals Age- and sex-specific reference intervals for the serum cystatin C/creatinine ratio in healthy children (0–18 years old)

2019 ◽  
Vol 47 (7) ◽  
pp. 3151-3159 ◽  
Author(s):  
Changjin Liu ◽  
Jing Wen ◽  
Jialin Xiang ◽  
Xuhong Ouyang ◽  
Yan Yang ◽  
...  
Keyword(s):  
Cystatin C ◽  
Pediatric Population ◽  
Age Groups ◽  
Serum Markers ◽  
Reference Intervals ◽  
Specific Reference ◽  
Healthy Children ◽  
Serum Samples ◽  
Serum Cystatin C ◽  
Age And Sex

Objective This study aimed to investigate serum levels of the cystatin C (CysC)/creatinine (Cr) ratio and renal serum markers (CysC, Cr, urea, and uric acid [UA]) for different ages and by sex. We also aimed to establish pediatric reference intervals for the serum CysC/Cr ratio. Methods Serum samples were collected from 4765 healthy children (0–18 years old). Serum markers of renal function were measured, and the CysC/Cr ratio of each participant was calculated and statistically analyzed. Results The renal marker CysC did not substantially change after 1 year old. Cr, urea, and UA levels generally increased with age. However, the serum CysC/Cr ratio steadily decreased with age. The CysC/Cr ratio showed significant differences in age among all age groups and varied with sex, except for in the 1 to 6-year-old groups. The overall serum CysC/Cr ratio in girls was higher than that in boys. Conclusion Reference intervals of the serum CysC/Cr ratio in the pediatric population were established. These intervals need to be partitioned by age and sex.

Processing-independent proANP measurement for low concentrations in plasma: reference intervals and effect of body mass index and plasma glucose

2017 ◽  
Vol 56 (1) ◽  
Author(s):  
Peter D. Mark ◽  
Ingrid Hunter ◽  
Dijana Terzic ◽  
Jens P. Goetze
Keyword(s):  
Body Mass Index ◽  
Body Mass ◽  
Plasma Glucose ◽  
Age Groups ◽  
Radioactive Tracer ◽  
Reference Intervals ◽  
Specific Reference ◽  
Regression Analyses ◽  
Obesity And Diabetes ◽  
Gender Specific

AbstractBackground:Decreased concentrations of pro-atrial-derived natriuretic peptides (proABP) in plasma have been associated with obesity and suggested as a predictor of type 2 diabetes. However, assays for measuring proANP are generally aimed to quantitate higher concentrations of proANP associated with cardiac disease. Therefore, we aimed to measure plasma proANP concentrations in a non-obese Scandinavian reference material and evaluate potential associations of plasma proANP with body mass index (BMI) and plasma glucose, respectively.Methods:We report an optimized processing-independent assay (PIA) for proANP in the lower concentration range. The assay was optimized by raising the amount of radioactive tracer and modifying the mixing ratio of resuspended plasma and buffer. Blood samples from a Scandinavian plasma cohort of 693 healthy subjects were then analyzed and age and gender-specific reference intervals were determined.Results:Simple linear regression analyses of proANP and both BMI and plasma glucose in fasting subjects displayed insignificant associations. Multiple regression analyses supported these findings. However, a higher median plasma concentration of proANP was noted among women <50 years compared to men, whereas no gender-specific differences were seen in other age groups.Conclusions:Our results show that in a healthy non-obese population, BMI and plasma glucose in fasting subjects do not affect plasma proANP concentrations. Our method should be considered for future studies on low proANP concentration studies, e.g. in obesity and diabetes.

Immunoglobulin G (IgG) and IgG subclass reference intervals in children, using Optilite® reagents

2018 ◽  
Vol 56 (8) ◽  
pp. 1319-1327 ◽  
Author(s):  
Olivier Grunewald ◽  
Benjamin Lopez ◽  
Séverine Brabant ◽  
Stéphanie Rogeau ◽  
Antoine Deschildre ◽  
...  
Keyword(s):  
Immunoglobulin G ◽  
Age Groups ◽  
Reference Intervals ◽  
Igg Subclasses ◽  
Specific Reference ◽  
Igg Subclass ◽  
Serum Samples ◽  
Gender Specific Differences ◽  
Specific Igg ◽  
Changes Over Time

Abstract Background: Immunoglobulin G (IgG) and IgG subclass assays are indicated in patients with suspected primary immunodeficiency (PID). Commercially available assays for IgG subclass determination are calibrated against various preparations, and so specific reference values are required for each of them. Using Optilite® reagents from The Binding Site Group Ltd., we sought to determine the pediatric IgG and IgG subclass reference intervals with respect to the ERM-DA470k certified reference material. Methods: Levels of IgG and IgG subclasses were analyzed in serum samples collected from a large cohort of PID-free children and adolescents. Reference intervals were calculated for previously published age groups (6–12 months, 12–18 months, 18 months–2 years, 2–3 years, 3–4 years, 4–6 years, 6–9 years, 9–12 years and 12–18 years), according to the Clinical and Laboratory Standards Institute’s C28-A3c protocol. Results: A total of 456 serum samples were analyzed. The correlation between the total IgG and the sum of the IgG subclasses was good (r2=0.96). No statistically significant gender-specific differences were observed. Our results for the changes over time in IgG and IgG subclass levels are consistent with previous reports. The differences between our lower/upper reference limits and those in the literature are probably due to variations in calibration. Conclusions: Our present results provide a reliable basis for the diagnosis of PIDs in childhood and for the accreditation of laboratories using Optilite® immunoturbidimetric reagents for IgG subclass measurement. Laboratory scientists and clinicians should be aware of the need for manufacturer-specific IgG subclass reference intervals.

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.

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.

Mining of hospital laboratory information systems: a model study defining age- and gender-specific reference intervals and trajectories for plasma creatinine in a pediatric population

2015 ◽  
Vol 53 (10) ◽  
Author(s):  
Karen Søeby ◽  
Peter Bjødstrup Jensen ◽  
Thomas Werge ◽  
Steen Sørensen
Keyword(s):  
Pediatric Population ◽  
Laboratory Data ◽  
Age Groups ◽  
Reference Intervals ◽  
Repeated Measurements ◽  
Plasma Creatinine ◽  
Specific Reference ◽  
Healthy Population ◽  
Hospital Laboratory ◽  
Gender And Age

AbstractThe knowledge of physiological fluctuation and variation of even commonly used biochemical quantities in extreme age groups and during development is sparse. This challenges the clinical interpretation and utility of laboratory tests in these age groups. To explore the utility of hospital laboratory data as a source of information, we analyzed enzymatic plasma creatinine as a model analyte in two large pediatric hospital samples.Plasma creatinine measurements from 9700 children aged 0–18 years were obtained from hospital laboratory databases and partitioned into high-resolution gender- and age-groups. Normal probability plots were used to deduce parameters of the normal distributions from healthy creatinine values in the mixed hospital datasets. Furthermore, temporal trajectories were generated from repeated measurements to examine developmental patterns in periods of changing creatinine levels.Creatinine shows great age dependence from birth throughout childhood. We computed and replicated 95% reference intervals in narrow gender and age bins and showed them to be comparable to those determined in healthy population studies. We identified pronounced transitions in creatinine levels at different time points after birth and around the early teens, which challenges the establishment and usefulness of reference intervals in those age groups.The study documents that hospital laboratory data may inform on the developmental aspects of creatinine, on periods with pronounced heterogeneity and valid reference intervals. Furthermore, part of the heterogeneity in creatinine distribution is likely due to differences in biological and chronological age of children and should be considered when using age-specific reference intervals.

scholarly journals Recommended changes of the current version of the German Rili-BAEK

2019 ◽  
Vol 43 (5) ◽  
pp. 225-233 ◽  
Author(s):  
Christian Beier
Keyword(s):  
Quality Assurance ◽  
Statistical Significance ◽  
Reference Intervals ◽  
Control Measures ◽  
Medical Laboratory ◽  
Patient Specific ◽  
Internal Quality ◽  
Specific Reference ◽  
Special Focus ◽  
Age Related

Abstract A number of improvement proposals and corrections of the German Rili-BAEK (Guideline of the German Medical Association on Quality Assurance in Medical Laboratory Examinations) are discussed with special focus on the internal and external quality assurance (IQA/EQA) as well as reference intervals for quantitative results. Particular attention is paid to reconsider the retrospective analysis of control measurements. Such an analysis can be very useful to monitor establishing errors of measurement even before they become critical. The present method “Quadratischer Mittelwert der Messabweichung (QMMA)” has proved to be ineffective. Furthermore, the current idea of a common limit for single control measures and the retrospective statistics must be revised. As a more sophisticated concept, the novel Adaptive Retrospective Monitoring (ARM) has been developed. ARM is recommended as the new minimum requirement for the entire internal quality assurance. Further proposals to enhance clarity are given concerning the release decisions of medical devices and the EQA. Individualized medicine begins with a patient-specific interpretation of analytic results. This requires standardized subgroup-specific reference intervals with smooth age-related adaptations. Only large laboratories are able to ensure the desired specificity and a sufficient statistical significance of self-developed in-laboratory reference intervals. Hence, the need of a central database for harmonized reference intervals is discussed and recommended. Suitable and consistent reference intervals are also an essential prerequisite for unitless laboratory values like the zlog value.

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