From Population to Subject-Specific Reference Intervals
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ABSTRACT:
SUBMITTER: Krzhizhanovskaya V
PROVIDER: S-EPMC7303731 | biostudies-literature | 2020 May
REPOSITORIES: biostudies-literature
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Project description:BackgroundLeptin is a peptide hormone secreted by adipose tissue and is an important determinant of obesity and its complications. The purpose of this study was to establish sex- and body mass index (BMI)-specific reference intervals for serum leptin in a Chinese population and investigate the factors influencing leptin concentrations.MethodsFasting serum leptin levels were assayed in 469 men and 773 women from randomly sampled Chinese residents. Blood glucose, insulin, hemoglobin A1c (HbA1c), liver enzymes, blood lipid profiles, creatinine, and uric acid (UA) levels were measured. Pearson's correlation coefficient and multiple linear regression analyses were used to estimate the relationship between serum leptin level and other variables. The reference intervals were determined by the 2.5th and 97.5th percentiles.ResultsThe mean ± standard deviation serum leptin level was much higher in women (20.92 ± 12.96 ng/mL) than in men (6.45 ± 5.53 ng/mL). The reference interval of serum leptin was 0.33-19.85 ng/mL in men and 3.60-54.86 ng/mL in women. The specific reference intervals of serum leptin in men with BMI of 20 to < 25 and 25 to < 27.5 kg/m2 were 0.42-12.32 and 2.17-20.22 ng/ml, respectively. The specific reference intervals of serum leptin in women with BMI of 20 to < 25 and 25 to < 27.5 kg/m2 were 4.11-38.09 and 8.27-48.66 ng/ml, respectively. BMI was significantly correlated with Ln (leptin) both in men (r = 0.698, P < 0.001) and women (r = 0.626, P < 0.001). In multivariate linear regression analysis, serum leptin was correlated with BMI, homeostasis model assessment of insulin resistance (HOMA-IR), UA in women, and plus triglyceride (TG) in men. The variance in serum leptin levels could be partially explained by these variables in both women (adjusted R2 = 0.447) and men (adjusted R2 = 0.552). In participants with leptin levels higher than the reference intervals, significantly higher levels of HOMA-IR, low-density lipoprotein cholesterol (LDL-C), UA, a higher proportion of central obesity (waist circumference [WC] > 90 cm), and metabolic syndrome were found in men, and significantly higher levels of HOMA-IR, UA and a higher proportion of central obesity (WC > 85 cm) were found in women.ConclusionThis is the first study to establish sex- and BMI-specific reference intervals of leptin for both sexes in a large Chinese population. Serum concentration of leptin was predicted by BMI, HOMA-IR, UA in women, and TG in men.
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Project description:Reference intervals for laboratory test results have to be appropriate for the population in which they are used to be clinically useful. While sex and age are established partitioning criteria, patients' origin also influences laboratory test results, but is not commonly considered when creating or applying reference intervals. In the German population, stratification for ethnicity is rarely performed, and no ethnicity-specific hematology reference intervals have been reported yet. In this retrospective study, we investigated whether specific reference intervals are warranted for the numerically largest group of non-German descent, individuals originating from Turkey. To this end, we analyzed 1,314,754 test results from 167,294 patients from six German centers. Using a name-based algorithm, 1.9% of patients were identified as originating from Turkey, in line with census data and the algorithm's sensitivity. Reference intervals and their confidence intervals were calculated using an indirect data mining approach, and Turkish and non-Turkish reference limits overlapped completely or partially in nearly all analytes, regardless of age and sex, and only 5/144 (3.5%) subgroups' reference limits showed no overlap. We therefore conclude that the current practice of using common reference intervals is appropriate and allows correct clinical decision-making in patients originating from Turkey.
| S-EPMC8548501 | biostudies-literature
Project description:BackgroundThe results of clinical laboratory tests are an essential component of medical decision-making. To guide interpretation, test results are returned with reference intervals defined by the range in which the central 95% of values occur in healthy individuals. Clinical laboratories often set their own reference intervals to accommodate variation in local population and instrumentation. For some tests, reference intervals change as a function of sex, age, and self-identified race and ethnicity.MethodsIn this work, we develop a novel approach, which leverages electronic health record data, to identify healthy individuals and tests for differences in laboratory test values between populations.ResultsWe found that the distributions of >50% of laboratory tests with currently fixed reference intervals differ among self-identified racial and ethnic groups (SIREs) in healthy individuals.ConclusionsOur results confirm the known SIRE-specific differences in creatinine and suggest that more research needs to be done to determine the clinical implications of using one-size-fits-all reference intervals for other tests with SIRE-specific distributions.
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Project description:BackgroundThere are racial, ethnic and geographical differences in complete blood count (CBC) reference intervals (RIs) and therefore it is necessary to establish RIs that are population specific. Several studies have been carried out in Africa to derive CBC RIs but many were not conducted with the rigor recommended for RI studies hence limiting the adoption and generalizability of the results.MethodBy use of a Beckman Coulter ACT 5 DIFF CP analyser, we measured CBC parameters in samples collected from 528 healthy black African volunteers in a largely urban population. The latent abnormal values exclusion (LAVE) method was used for secondary exclusion of individuals who may have had sub-clinical diseases. The RIs were derived by both parametric and non-parametric methods with and without LAVE for comparative purposes.ResultsHaemoglobin (Hb) levels were lower while platelet counts were higher in females across the 4 age stratifications. The lower limits for Hb and red blood cell parameters significantly increased after applying the LAVE method which eliminated individuals with latent anemia and inflammation. We adopted RIs by parametric method because 90% confidence intervals of the RI limits were invariably narrower than those by the non-parametric method. The male and female RIs for Hb after applying the LAVE method were 14.5-18.7 g/dL and 12.0-16.5 g/dL respectively while the platelet count RIs were 133-356 and 152-443 x10(3) per μL respectively.ConclusionConsistent with other studies from Sub-Saharan Africa, Hb and neutrophil counts were lower than Caucasian values. Our finding of higher Hb and lower eosinophil counts compared to other studies conducted in rural Kenya most likely reflects the strict recruitment criteria and healthier reference population after secondary exclusion of individuals with possible sub-clinical diseases.
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Project description:BackgroundWe established age-group-specific reference intervals for serum anti-Müllerian hormone (AMH) levels in a Korean population and investigated the effectiveness of AMH assay for polycystic ovary syndrome (PCOS) diagnosis.MethodsWe analyzed serum levels of AMH, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) from 1540 Korean women. Subjects were divided into three groups: healthy, benign gynecologic diseases, and PCOS. Age-group-specific reference intervals and AMH diagnostic performance were estimated.ResultsThe PCOS group had a median AMH level of 7.0 µg/L, which was higher than for the healthy (1.8 µg/L) and the benign gynecologic diseases (2.7 µg/L) groups. The upper 97.5% reference limits for age groups 12-20 years, 21-34 years, and 35-46 years were 13.2 µg/L, 15.8 µg/L, and 6.6 µg/L, respectively. The area under the curve (AUC) values to estimate AMH ability to discriminate PCOS from healthy women for each age group were 0.741, 0.785, and 0.789, respectively. AUCs for LH/FSH were 0.719, 0.672, and 0.590.ConclusionsThe better diagnostic ability of AMH over LH/FSH in women of late childbearing ages indicates that age and other clinical characteristics should be considered when interpreting these test results.
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Project description:BackgroundPrediction of End-Systole time is of utmost importance for cardiac MRI to correctly associate acquired k-space lines during reconstruction of cine acquisitions. This prediction is usually based on the patient's heart rate using Weissler's formula, which was calibrated by linear regression within a population and cannot account for individual variability.ObjectiveWe propose an automatic method to build a personalized model that better predicts end-systole.MethodsA phase contrast sequence was modified to acquire only central k-space line with 6.6ms temporal resolution, in a slice passing through the aorta during 128 heartbeats in 35 subjects. Segmentation of aorta and detection of end of systolic ejection was automatic. Duration of electromechanical systole duration as function of heart rate was determined for each subject separately.ResultsIn comparison with the global models, the adapted cardiac model predicted significantly better both echocardiographic end-systolic reference (bias = 0ms vs 17ms, p<0.001) and MRI measurements (bias = 6.8ms vs 17ms). Favorable impact was shown on the cine reconstruction of the 5 subjects with the higher cardiac variability (p = 0.02).ConclusionsPersonalization of cardiac model to the subject is feasible in MRI and reduces the error of prediction of systole.
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Project description:BackgroundThis 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.
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