scholarly journals Sources of variation and establishment of Russian reference intervals for major hormones and tumor markers

PLoS ONE ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. e0234284
Author(s):  
Anna Ruzhanskaya ◽  
Kiyoshi Ichihara ◽  
Svetlana Evgina ◽  
Irina Skibo ◽  
Nina Vybornova ◽  
...  
Keyword(s):  
Tumor Markers ◽  
Sex Hormones ◽  
Parametric Method ◽  
Smoking Habit ◽  
Bimodal Distribution ◽  
Reference Intervals ◽  
Careful Consideration ◽  
Russian Population ◽  
Serum Samples ◽  
Sources Of Variation

Objectives A multicenter study was organized to explore sources of variation (SVs) of reference values (RVs) for 22 major immunochemistry analytes and to determine reference intervals (RIs) for the Russian population. Methods According to IFCC Committee on Reference Intervals and Decision Limits (C-RIDL) protocol, 758 healthy volunteers were recruited in St. Petersburg, Moscow, and Yekaterinburg. Serum samples were tested for five tumor markers, 17 hormones and related tests by Beckman Coulter’s UniCel DxI 800 immunochemistry analyzer. SVs were explored using multiple regression analysis and ANOVA. Standard deviation ratio (SDR) of 0.4 was used as primary guide for partitioning RIs by gender and age. Results SDR for between-city difference was <0.4 for all analytes. Secondary exclusion of individuals was done under the following conditions: for female sex-hormones, those with contraceptives (8%); for CA19-9, those supposed to have negative Lewis blood-group (10.5% males and 11.3% females); for insulin, those with BMI≥28 kg/m2 (31%); for the thyroid panel, those with anti-thyroid antibodies (10.3% males; 24.5% females), for CEA those with smoking habit (30% males and 16% females). Gender-specific RIs were required for all analytes except CA19-9, CA15-3, thyroid-related tests, parathyroid hormone, and insulin. Age-specific RIs were required for alpha-fetoprotein, CEA, all sex-hormones for females, FSH and progesterone for both sexes. RIs were generally derived by parametric method after Gaussian transformation using modified Box-Cox formula. Exceptions were growth hormone, estradiol for females in postmenopause, and progesterone for females in premenopause, for which nonparametric method was required due to bimodal distribution and/or insufficient detection limit. Conclusion RIs for major hormones and tumor markers specific for the Russian population were derived based on the up-to-date internationally harmonized protocol by careful consideration of analyte-specific SVs.

scholarly journals Sources of variation and establishment of Russian reference intervals for major hormones and tumor markers

2020 ◽  
Author(s):  
Anna Ruzhanskaya ◽  
Kiyoshi Ichihara ◽  
Svetlana Evgina ◽  
Irina Skibo ◽  
Nina Vybornova ◽  
...  
Keyword(s):  
Tumor Markers ◽  
Sex Hormones ◽  
Parametric Method ◽  
Bimodal Distribution ◽  
Reference Intervals ◽  
Careful Consideration ◽  
Russian Population ◽  
Serum Samples ◽  
Female Sex Hormones ◽  
Sources Of Variation

AbstractObjectivesA multicenter study was organized to explore sources of variation (SVs) of reference values (RVs) for 24 major immunochemistry analytes and to determine reference intervals (RIs) for the Russian population.MethodsAccording to IFCC Committee on Reference Intervals and Decision Limits (C-RIDL) protocol, 793 healthy volunteers were recruited in St. Petersburg, Moscow, and Yekaterinburg. Serum samples were tested for five tumor markers, 19 hormones and related tests by Beckman Coulter’s UniCel DxI 800 immunochemistry analyzer. SVs were explored using multiple regression analysis and ANOVA. Standard deviation ratio (SDR) of 0.4 was used as primary guide for partitioning RIs by gender and age.ResultsSDR for between-city difference was <0.4 for all analytes. Secondary exclusion of individuals was done under the following conditions: for female sex-hormones, those with contraceptives (8%); for CA19-9, those supposed to have negative Lewis blood-group (10.5%); for insulin, those with BMI≥28 kg/m2 (29.9%); for the thyroid panel, those with anti-thyroid antibodies (10.3% in males; 24.5% in females). Gender-specific RIs were required for all analytes except CA19-9, CA15-3, thyroid-related tests, parathyroid hormone, and insulin. Age-specific RIs were required for α-fetoprotein and all sex-hormones except testosterone. RIs were generally derived by parametric method after Gaussian transformation using modified Box-Cox formula. Exceptions were growth hormone, estradiol, and progesterone, for which nonparametric method was required due to bimodal distribution and/or insufficient detection limit.ConclusionRIs for major hormones and tumor markers specific for the Russian population were derived based on the up-to-date internationally harmonized protocol by careful consideration of analyte-specific SVs.

Establishment of reference intervals for immunoassay analytes of adult population in Saudi Arabia

2020 ◽  
Vol 58 (8) ◽  
pp. 1302-1313 ◽  
Author(s):  
Anwar Borai ◽  
Kiyoshi Ichihara ◽  
Abdulaziz Masaud ◽  
Waleed Tamimi ◽  
Suhad Bahijri ◽  
...  
Keyword(s):  
Vitamin D ◽  
Saudi Arabia ◽  
Adult Population ◽  
Reference Intervals ◽  
Careful Consideration ◽  
Upper Limits ◽  
Sources Of Variation ◽  
Vitamin D Supplements ◽  
Saudi Arabians ◽  
Abbott Architect

AbstractBackgroundThis is a second part of report on the IFCC global multicenter study conducted in Saudi Arabia to derive reference intervals (RIs) for 20 immunoassay analytes including five tumor makers, five reproductive, seven other hormones and three vitamins.MethodsA total of 826 apparently healthy individuals aged ≥18 years were recruited in three clinical laboratories located in western, central and eastern Saudi Arabia using the protocol specified for the global study. All serum specimens were measured using Abbott, Architect analyzers. Multiple regression analysis (MRA) was performed to explore sources of variation of each analyte: age, body mass index (BMI), physical exercise and smoking. The magnitude of variation of reference values (RVs) attributable to sex, age and region was calculated by ANOVA as a standard deviation ratio (SDR). RIs were derived by the parametric (P) method.ResultsMRA revealed that region, smoking and exercise were not relevant sources of variation for any analyte. Based on SDR and actual between-sex differences in upper limits (ULs), we chose to partition RIs by sex for all analytes except for α-fetoprotein and parathyroid hormone (PTH). Age-specific RIs were required in females for ferritin, estradiol, progesterone, testosterone, follitropin, luteotropin and prolactin (PRL). With prominent BMI-related increase, RIs for insulin and C-peptide were derived after excluding individuals with BMI > 32 kg/m2. Individuals taking vitamin D supplements were excluded in deriving RIs for vitamin D and PTH.ConclusionsRIs of major immunoassay analytes specific for Saudi Arabians were established in careful consideration of various biological sources of variation.

scholarly journals Reference intervals for 33 biochemical analytes in healthy Indian population: C-RIDL IFCC initiative

2018 ◽  
Vol 56 (12) ◽  
pp. 2093-2103 ◽  
Author(s):  
Swarup A.V. Shah ◽  
Kiyoshi Ichihara ◽  
Alpa J. Dherai ◽  
Tester F. Ashavaid
Keyword(s):  
Parametric Method ◽  
Reference Intervals ◽  
Specific Reference ◽  
Appreciable Effect ◽  
Test Results ◽  
Gender And Age ◽  
Sources Of Variation ◽  
Overnight Fasting ◽  
Nested Analysis ◽  
Non Parametric

Abstract Background In 2011, the IFCC Committee on Reference Intervals and Decision Limits (C-RIDL) initiated a worldwide multicenter study on references values facilitating the implementation of country-specific reference intervals (RIs). There has been no well-designed RI study in India. This study aims to derive RIs for 33 major biochemical analytes in carefully selected healthy Indians as defined in C-RIDL protocol. Methods A total of 512 healthy Indians were recruited. Sera collected from overnight fasting blood samples were measured collectively for the analytes. Multiple regression analysis (MRA) and nested analysis of variance (ANOVA) were used to identify the potential sources of variation (SV) of test results. RI were derived by both parametric and non-parametric methods for comparison. The need for secondary exclusion by latent abnormal values exclusion (LAVE) method was examined. Results MRA results indicated that both age and BMI were apparent SV for many analytes in both sexes. ANOVA revealed that partition of RIs by gender and age was required for 17 analytes (TC, HDL-C, TG, hsCRP, ALB, AST, ALT, ALP, GGT, TBil, Urea, CRE, UA, Fe, TTR, CK and IgM) and 5 (Glu, ALB, TC, ALP and Urea), respectively. RIs by parametric method were generally narrower than by non-parametric method, reflecting distorted peripheral distributions of test results. The LAVE method had no appreciable effect on RIs possibly due to inconsistency among abnormal values of related analytes. Conclusions This study has for the first time provided comprehensive RIs information in healthy Indians. The final RIs adopted were those derived by parametric method without LAVE procedure.

A multicenter nationwide reference intervals study for common biochemical analytes in Turkey using Abbott analyzers

2014 ◽  
Vol 52 (12) ◽  
Author(s):  
Yesim Ozarda ◽  
Kiyoshi Ichihara ◽  
Diler Aslan ◽  
Hulya Aybek ◽  
Zeki Ari ◽  
...  
Keyword(s):  
Reference Values ◽  
Parametric Method ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Turkish Population ◽  
Reference Intervals ◽  
Test Results ◽  
Age Related ◽  
Sources Of Variation ◽  
Exclusion Method

AbstractA nationwide multicenter study was organized to establish reference intervals (RIs) in the Turkish population for 25 commonly tested biochemical analytes and to explore sources of variation in reference values, including regionality.Blood samples were collected nationwide in 28 laboratories from the seven regions (≥400 samples/region, 3066 in all). The sera were collectively analyzed in Uludag University in Bursa using Abbott reagents and analyzer. Reference materials were used for standardization of test results. After secondary exclusion using the latent abnormal values exclusion method, RIs were derived by a parametric method employing the modified Box-Cox formula and compared with the RIs by the non-parametric method. Three-level nested ANOVA was used to evaluate variations among sexes, ages and regions. Associations between test results and age, body mass index (BMI) and region were determined by multiple regression analysis (MRA).By ANOVA, differences of reference values among seven regions were significant in none of the 25 analytes. Significant sex-related and age-related differences were observed for 10 and seven analytes, respectively. MRA revealed BMI-related changes in results for uric acid, glucose, triglycerides, high-density lipoprotein (HDL)-cholesterol, alanine aminotransferase, and γ-glutamyltransferase. Their RIs were thus derived by applying stricter criteria excluding individuals with BMI >28 kg/mWith the lack of regional differences and the well-standardized status of test results, the RIs derived from this nationwide study can be used for the entire Turkish population.

scholarly journals Establishment of reference intervals of biochemical analytes for South African adults: a study conducted as part of the IFCC global multicentre study on reference values

2021 ◽  
pp. 8-23
Author(s):  
FC Smit ◽  
K Ichihara ◽  
J George ◽  
E Blanco-Blanco ◽  
M Hoffmann ◽  
...  
Keyword(s):  
South African ◽  
Reference Values ◽  
Clinical Chemistry ◽  
Parametric Method ◽  
Density Lipoprotein ◽  
Reference Intervals ◽  
Mixed Ancestry ◽  
Serum Samples ◽  
Age Related ◽  
Non Parametric

Objective: This study was conducted as a part of the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) global study for establishing reference intervals (RIs) of common laboratory tests for the South African population considering gender, ethnicity, age and body mass index (BMI). Methods: The researchers recruited 1 143 apparently healthy volunteers aged 18–65: 551 African (Afr) and 592 non-African (NAfr) (comprising 383 Caucasian and 209 Mixed Ancestry). Serum samples were measured for 40 chemistry and immunochemistry analytes. The standard deviation ratio (SDR) guided the need for partitioning reference values according to gender, ethnicity and age using a threshold of ≥ 0.4. The latent abnormal values exclusion (LAVE) method was applied to reduce influences of latent diseases before deriving RIs using both parametric and non-parametric methods. Results: Based on SDRsex, males showed higher albumin, uric acid, creatinine, AST, CK and ferritin. Based on SDRRC, Afr compared to NAfr showed (i) higher total protein, amylase, CRP, immunoglobulin G and A and (ii) lower total bilirubin, total cholesterol, low-density lipoprotein cholesterol (LDL-C), ALT and cholinesterase. Both age-related changes in glucose and LDL-C, and BMI-related changes in ALT, ALP and LDH were more prominent in NAfr. RIs were determined according to gender, age and ethnicity. The LAVE method was effective in lowering the upper RI limits (UL) of nutritional markers such as γGT and CRP. Compared to the non-parametric method, the parametric method gave narrower confidence intervals of ULs for analytes with skewed distributions. Conclusion: Establishing RIs by considering ethnicity was essential in many analytes in South Africa. Age and BMI-related changes differed greatly between Afr and NAfr.

scholarly journals Determination of reference intervals for knee motor functions specific to patients undergoing knee arthroplasty

PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0249564
Author(s):  
Hideyuki Ito ◽  
Kiyoshi Ichihara ◽  
Kotaro Tamari ◽  
Tetsuya Amano ◽  
Shigeharu Tanaka ◽  
...  
Keyword(s):  
Motor Function ◽  
Knee Arthroplasty ◽  
Parametric Method ◽  
Reference Intervals ◽  
Variable Degree ◽  
Test Results ◽  
Timed Up And Go ◽  
Motor Functions ◽  
Age Related ◽  
Sources Of Variation

Background In patients with knee osteoarthritis (KOA) undergoing knee arthroplasty (KA), lower-limb motor function tests are commonly measured during peri-surgical rehabilitation. To clarify their sources of variation and determine reference intervals (RIs), a multicenter study was performed in Japan. Methods We enrolled 545 KOA patients (127 men; 418 women; mean age 74.2 years) who underwent KA and followed a normal recovery course. The surgical modes included total KA (TKA), minimally invasive TKA (MIS-TKA), and unicompartmental KA (UKA). Motor functions measured twice before and two weeks after surgery included timed up-and-go (TUG), maximum walking speed (MWS), extensor and flexor muscle strength (MS), and knee range of motion (ROM). Multiple regression analysis was performed to evaluate their sources of variation including sex, age, BMI, and surgical mode. Magnitude of between-subgroup differences was expressed as SD ratio (SDR) based on 3-level nested ANOVA. SDR≥0.4 was set as the threshold for requiring RIs specific for each subgroup. Results Before surgery, age-related changes exceeding the threshold were observed for TUG and MWS. Between-sex difference was noted for extensor and flexor MS, but extension and flexion ROMs were not influenced by sex or age. After surgery, in addition to similar influences of sex and age on test results, surgical modes of UKA and MIS-TKA generally had a favorable influence on MWS, extensor MS, and flexion ROM. All motor function test results showed a variable degree of skewness in distribution, and thus RIs were basically derived by the parametric method after Gaussian transformation of test results. Conclusions This is the first study to determine RIs for knee motor functions specific to KOA patients after careful consideration of their sources of variation and distribution shapes. These RIs facilitate objective implementation of peri-surgical rehabilitation and allow detection of patients who deviate from the normal course of recovery.

scholarly journals Biological variation and reference change value data for serum copper, zinc and selenium in Turkish adult population

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Ceylan Bal ◽  
Serpil Erdogan ◽  
Gamze Gök ◽  
Cemil Nural ◽  
Betül Özbek ◽  
...  
Keyword(s):  
Adult Population ◽  
Reference Intervals ◽  
Serum Copper ◽  
Biological Variation ◽  
Serum Samples ◽  
Reference Change Value ◽  
Index Of Individuality ◽  
Copper Zinc ◽  
Clinically Significant ◽  
Analytical Variation

Abstract Objectives Calculation of biological variation (BV) components is very important in evaluating whether a test result is clinically significant. The aim of this study is to analyze BV components for copper, zinc and selenium in a cohort of healthy Turkish participants. Methods A total of 10 serum samples were collected from each of the 15 healthy individuals (nine female, six male), once a week, during 10 weeks. Copper, zinc and selenium levels were analyzed by atomic absorption spectrometer. BV parameters were calculated with the approach suggested by Fraser. Results Analytical variation (CVA), within-subject BV (CVI), between-subject BV (CVG) values were 8.4, 7.1 and 4.3 for copper; 4.2, 9.1 and 13.7 for zinc; 7.6, 2.5 and 6.9 for selenium, respectively. Reference change values (RCV) were 30.46, 27.56 and 22.16% for copper, zinc and selenium, respectively. The index of individuality (II) values were 1.65, 0.66 and 0.36 for copper, zinc and selenium, respectively. Conclusions According to the results of this study, traditional reference intervals can be used for copper but we do not recommend using it for zinc and selenium. We think that it would be more accurate to use RCV value for zinc and selenium in terms of following significant changes in recurrent results of a patient.

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 Establishment of Reference Intervals of Clinical Chemistry Analytes for the Adult Population in Egypt

2020 ◽  
Author(s):  
Heba Baz ◽  
Kiyoshi Ichihara ◽  
May Selim ◽  
Ahmed Awad ◽  
Sarah Aglan ◽  
...  
Keyword(s):  
Regional Differences ◽  
Clinical Chemistry ◽  
Adult Population ◽  
Middle Eastern ◽  
Low Density Lipoprotein ◽  
Parametric Method ◽  
Density Lipoprotein ◽  
Reference Intervals ◽  
Lipoprotein Cholesterol ◽  
Multiple Regions

AbstractBackgroundThis is the first Egyptian nationwide study for derivation of reference intervals (RIs) for 34 major chemistry analytes. It was conducted as a part of the global initiative by the IFCC Committee on Reference Intervals and Decision Limits (C-RIDL) for establishing country-specific RIs based on a harmonized protocol.Methods691 apparently healthy volunteers aged ≥18 years were recruited from multiple regions in Egypt. Serum specimens were analyzed in two centers. The harmonization and standardization of test results were achieved by measuring value-assigned serum panel provided by C-RIDL. The RIs were calculated by parametric method. Sources of variation of reference values (RVs) were evaluated by multiple regression analysis. The need for partitioning by sex, age, and region was judged primarily by standard deviation ratio (SDR).ResultsGender-specific RIs were required for six analytes including total bilirubin (TBil), aspartate and alanine aminotransferase (AST, ALT). Seven analytes required age-partitioning including glucose and low-density lipoprotein cholesterol (LDL-C)., Regional differences were observed between northern and southern Egypt for direct bilirubin, glucose, and high-density-lipoprotein cholesterol (HDL-C) with all their RVs lower in southern Egypt. Compared with other collaborating countries, the features of Egyptian RVs were lower HDL-C and TBil and higher TG and C-reactive protein. In addition, BMI showed weak association with most of nutritional markers. These features were shared with two other Middle Eastern countries: Saudi Arabia and Turkey.ConclusionThe standardized RIs established by this study can be used as common Egyptian RI, except for a few analytes that showed regional differences. Despite high prevalence of obesity among Egyptians, their RVs of nutritional markers are less sensitive to increased BMI, compared to other collaborating countries.

Pediatric reference intervals for 1,25-dihydroxyvitamin D using the DiaSorin LIAISON XL assay in the healthy CALIPER cohort

2018 ◽  
Vol 56 (6) ◽  
pp. 964-972 ◽  
Author(s):  
Victoria Higgins ◽  
Dorothy Truong ◽  
Nicole M.A. White-Al Habeeb ◽  
Angela W.S. Fung ◽  
Barry Hoffman ◽  
...  
Keyword(s):  
Children And Adolescents ◽  
Critical Role ◽  
Reference Interval ◽  
Reference Intervals ◽  
Biologically Active ◽  
Specific Reference ◽  
Healthy Children ◽  
Serum Samples ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D

Abstract Background: 1,25-dihydroxyvitamin D (1,25(OH)2D), the biologically active vitamin D metabolite, plays a critical role in calcium and phosphate homeostasis. 1,25(OH)2D is measured to assess calcium and phosphate metabolism, particularly during periods of profound growth and development. Despite its importance, no reliable pediatric reference interval exists, with those available developed using adult populations or out-dated methodologies. Using the fully automated chemiluminescence immunoassay by DiaSorin, we established 1,25(OH)2D pediatric reference intervals using healthy children and adolescents from the CALIPER cohort. Methods: Serum samples from healthy subjects (0 to <19 years) were analyzed for 1,25(OH)2D using the DiaSorin LIAISON XL assay and age-specific reference intervals were established. The Mann-Whitney U-test was used to determine seasonal differences. Pooled neonatal and infantile samples were quantified using liquid chromatography tandem mass spectrometry (LC-MS/MS) to determine if elevated concentrations during the first year of life may be attributed to cross-reacting moieties. Results: Three reference interval age partitions were required with highest levels in subjects 0 to <1 year (77–471 pmol/L), which declined and narrowed after 1 year (113–363 pmol/L) and plateaued at 3 years (108–246 pmol/L). 1,25(OH)2D concentration was not significantly affected by seasonal variation or sex. Elevated 1,25(OH)2D concentrations in neonatal and infantile samples may be the result of an interfering substance. The absence of 3-epi-1,25-dihydroxyvitamin D in the pooled samples makes it unlikely to be the interfering moiety. Conclusions: Pediatric reference intervals for 1,25(OH)2D were established to improve test result interpretation in children and adolescents. 1,25(OH)2D is elevated in a proportion of neonates and infants, which may be the result of a cross-reacting moiety.

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