Hoffmann Method Research Articles

Reference intervals of adjacent disc height in fresh osteoporotic vertebral compression fractures and the association with postoperative adjacent segment complications: a quantitative study in Chinese postmenopausal women

BackgroundPreoperative adjacent disc height (DH) was found as an independent risk factor for adjacent segment degeneration (ASD) after percutaneous kyphoplasty (PKP), indicating the preoperative status of the adjacent intervertebral discs may be closely related to adjacent segment complications. To establish the reference intervals (RIs) for adjacent DH of fresh osteoporotic vertebral compression fracture (OVCF) in Chinese postmenopausal women, and investigate the association with adjacent segment complications after PKP.MethodsConsecutive inpatients diagnosed with fresh OVCF between November 2015 and August 2023 were reviewed. The enrolled patients were divided into subgroups based on injured vertebral level; then, the cranial and caudal DH were measured. The characteristics of DH among subgroups were identified, and specific RIs were established using the indirect Hoffmann method. The associations between DH and adjacent segment complications were assessed using multivariate analysis.ResultsThe DH of the cranial disc was significantly lower than the corresponding caudal disc in all vertebral levels, which showed an increasing trend from T11 to L4. The RIs of DH were as follows: T11 (cranial), 2.14–5.14 mm; T11 (caudal), 2.64–5.89 mm; T12 (cranial), 2.69–5.77 mm; T12 (caudal), 3.18–6.57 mm; L1 (cranial), 3.05–6.59 mm; L1 (caudal), 3.40–8.29 mm; L2 (cranial), 3.68–8.36 mm; L2 (caudal), 4.57–9.78 mm; L3 (cranial), 4.53–8.92 mm; L3 (caudal), 5.26–10.07 mm; L4 (cranial), 4.70–11.42 mm; and L4 (caudal), 5.52–12.12 mm. Increased risks of adjacent segment complications after PKP were observed in patients with decreased adjacent DH.ConclusionThe estimated vertebral level and disc level-specific RIs for adjacent DH of fresh OVCF were established in the Chinese postmenopausal women population. A decrease in adjacent DH posed high risks of adjacent segment complications after PKP for treating OVCF.

Establishing Neuron-Specific Enolase Reference Intervals: A Comparative Analysis of Partitioned Approach- and Gender-Based Continuous Age- and Season-Related Models.

Background/Objectives: Static reference intervals (RIs) fail to capture the dynamic changes in bioanalytes. This study aimed to develop gender-based continuous age- and season-related RIs for neuron-specific enolase (NSE) using real-world data and to compare them with partitioned RIs. Methods: The NSE results from 4097 individuals were included after rigorous screening. Partitioned RIs were determined using the Hoffmann method. Generalized additive models for location, scale and shape (GAMLSS) were selected to develop continuous RIs. Results: The partitioned RIs are as follows: <16.4 µg/L for males aged ≥19 years; <14.47 µg/L for females aged 19-49 years; and <17.25 µg/L for females aged ≥50 years. For continuous RIs, NSE levels in males remain stable with age, while in females, NSE levels evidently increase around the age of 50. Although less impactful than age, seasonal changes still affect NSE levels. Dynamic changes and continuous RIs for NSE are visualized in this study. Conclusions: We developed gender-based continuous age- and season-integrated RIs for NSE in North China, highlighting the variation in NSE levels in females with age and season. Compared to static RIs, continuous RIs are more responsive to NSE, potentially enhancing the precision and individualization of health assessments.

Determination of Reference Intervals of Some Biochemistry Tests by the Bhattacharya and Hoffmann Methods.

Clinical laboratory tests are being evaluated with reference intervals (RI). Therefore, it is important that each laboratory determines and classifies its own reliable RI for each test to ensure an accurate and effective interpretation. The proposed method for determining RI is the "direct" approach, but it is a difficult, troublesome, time-consuming, and expensive method. An alternative approach is the "indirect" approach. In this study, we aimed to compare the RI values determined by the indirect method from the Calcium (Ca), Magnesium (Mg), Phosphate (P), 25-Hydroxy Vitamin D (25(OH)D), and Parathyroid hormone (PTH) test results with the RI provided by the manufacturer. A total of 1,520,314 Ca, Mg, P, 25(OH)D, and PTH test results, which were studied in our laboratory between January and November 2022, were included in the study. Data cleaning was done for individuals between the ages of 18 - 89, and only one record was allowed. The Tukey method was used to determine and exclude extreme values. Ca and Mg tests were divided into age groups (18 - 59 and 60 - 89 years), P, 25(OH)D, and PTH tests were divided into female - male groups. RI was calculated by using the Bhattacharya and Hoffmann methods. CLIA 19 acceptable limits were used to evaluate the compliance with the manufacturer's RI. The RI results obtained by applying the Bhattacharya and Hoffmann methods were found to be significantly consistent and compatible with each other. According to the manufacturer's RI, Ca and Mg were compatible with RI in both methods, P was considered compatible with PTH and 25(OH)D upper reference limit in the Bhattacharya method, P was considered compatible with 25(OH)D lower reference limit and PTH upper reference limit in the Hoffmann method, while 25(OH)D lower reference limit was found to be different in the Bhattacharya method, and 25(OH)D upper reference limit and PTH lower reference limit were found to be different in the P male group in the Hoffmann method. We believe that it is of great importance for each laboratory to determine the RI specific for the population they serve and to choose the analytical method they use according to age and gender while periodically updating them to interpret the test results correctly.

An observational association study between maternal homocysteine and pregnancy complications or perinatal outcomes with established trimester-specific reference intervals in pregnant women.

Elevated homocysteine (Hcy) level during pregnancy is positively associated with various gestational-specific diseases. However, there is no uniform standard for the reference interval (RI) of Hcy in pregnancy. From January 2017 to January 2019, 14,530 singleton pregnant women registered at our institute were included for the establishment of trimester-specific RIs of Hcy with both the nonparametric approach and the indirect Hoffmann method, followed by pregnancy outcome association analysis conducted with logistic regression. The serum Hcy level in the nonpregnant group was significantly higher than that of pregnant women. A relatively decreased Hcy concentration was observed in the second trimester when compared with that of the first or third trimester. The direct RIs of Hcy in the first or third, and second trimesters were 4.6 to 8.0 mmol/L (merged) and 4.0 to 6.4 mmol/L, respectively, which showed no significant difference compared with the RI derived from the indirect Hoffmann method. In the subsequent risk analysis, the first trimester Hcy was found to be negatively associated with GDM development; whereas the third trimester Hcy conferred increased risk of postpartum hemorrhage after delivery. Having established trimester-specific RIs, our study sheds light on the complicated roles of Hcy in pregnancy-related complications.

Consideration for Setting Reference Range for Adrenocorticotropic Hormone Test according to Blood Collection Time

Purpose: The reference range described in Adrenocorticotropic Hormone reagent used in our laboratory is 10-60 pg/mL at 8 a.m. to 10 a.m., and 6-30 pg/mL at 8 p.m. to 10 p.m. However, in the case of outpatients, blood is mainly collected between 10 a.m. and 6 p.m., accounting for 57.8% of the total. Therefore, This study is intended to help make a more accurate diagnosis by reevaluating the reference range provided by the manufacturer of the Adrenocorticotropic Hormone reagent and setting split-timed reference range. Materials and Methods: The patients collected blood before 10 a.m. were group A (68 people), and the patients collected blood after 10 a.m. were set to group B (80 people). A T-test was performed between groups to test their significance. And it was confirmed whether it was necessary to set the gender classification as a subgroup. The method of setting the reference range was calculated by the Bayesian’s method and the Hoffmann’s method. Results: The reference range of Group A was 8.6 to 60.6 pg/mL by the Bayesian’s method, and the Hoffmann’s method was 3.6 to 61.3 pg/mL. The reference range of Group B was 6.9 to 50.5 pg/mL when applying the Bayesian’s method, and the Hoffmann method’s was 2.3 to 48.9 pg/mL. Conclusion: This study was concluded that it was necessary to set the split-timed reference range. Through this study, the later the blood collection time, the lower the level of Adrenocorticotropic Hormone, indicating that blood collection time is important for patients with clinical significance. If a large number of subjects are selected and supplemented in the future, it is believed that systematic and accurate reference range can be set.

Elevated levels of renal function tests conferred increased risks of developing various pregnancy complications and adverse perinatal outcomes: insights from a population-based cohort study.

Physiological changes during pregnancy can affect the results of renal function tests (RFTs). In this population-based cohort study, we aimed to establish trimester-specific reference intervals (RIs) of RFTs in singleton and twin pregnancies and systematically investigate the relationship between RFTs and adverse pregnancy outcomes. The laboratory results of the first- and third-trimester RFTs, including blood urea nitrogen (BUN), serum uric acid (UA), creatinine (Crea) and cystatin C (Cys C), and the relevant medical records, were retrieved from 29,328 singleton and 840 twin pregnant women who underwent antenatal examinations from November 20, 2017 to January 31, 2021. The trimester-specific RIs of RFTs were estimated with both of the direct observational and the indirect Hoffmann methods. The associations between RTFs and pregnancy complications as well as perinatal outcomes were assessed by logistic regression analysis. Maternal RFTs showed no significant difference between the direct RIs established with healthy pregnant women and the calculated RIs derived from the Hoffmann method. In addition, elevated levels of RFTs were associated with increased risks of developing various pregnancy complications and adverse perinatal outcomes. Notably, elevated third-trimester RFTs posed strong risks of preterm birth (PTB) and fetal growth restriction (FGR). We established the trimester-specific RIs of RFTs in both singleton and twin pregnancies. Our risk analysis findings underscored the importance of RFTs in identifying women at high risks of developing adverse complications or outcomes during pregnancy.

Chinese pediatric and adolescent reference intervals of vitamin E based on real-world physical examination data

ObjectivesTo establish the reference interval (RI) of vitamin E for Chinese children and adolescents. Materials and methodsSerum tocopherol samples were examined using high performance liquid chromatography in third-party clinical laboratory institutions. Using real-world data from multi-center clinical laboratory institutions in China, the distribution parameters of vitamin E levels were described and the RI was calculated using three algorithms. ResultsA total of 756,766 cases were included in the analysis, including 435,561 males and 321,205 females. The median of vitamin E in infants younger than 4 years of age initially increased but subsequently decreased; while its levels in children between 4 and 11 years of age remained relatively stable despite progressing in age (approximately 7.4–7.8 mg/L). After the start of puberty, the difference, relative to sex, gradually became apparent, and the median vitamin E levels in females was higher than in males. The differences of vitamin E levels between different regions and samples in different seasons had no clinical significance. The RI of vitamin E for children aged 0–18 years in China was 4.5–11.1 mg/L based on expectation–maximization algorithm. The RI established by the Hoffmann method was 4.6–12.8 mg/L. ConclusionThe age- and sex-specific RIs of vitamin E were established by an indirect approach. The RIs established by EM algorithms could be used as an alternative to establish RIs based on real-world data.

Reference Intervals of Thyroid Hormones During Pregnancy Established by Three Statistical Methods.

Monitoring the thyroid hormones during pregnancy is of great importance for fetal growth and development. Throughout the whole pregnancy, there is constant fluctuation in the thyroid hormone reference intervals (RIs). The purpose of this study is to determine method- and trimester-specific RIs for thyroid-stimulating hormone, free thyroxine, and free triiodothyronine in pregnant women in China. In this study, 2,167 women with normal pregnancies (first trimester, n = 299; second trimester, n = 1,032; third trimester, n = 836) and 4,231 healthy nonpregnant women subjects were recruited. Serum thyroid-stimulating hormone (TSH), free thyroxine (fT4), and free triiodothyronine (fT3) concentrations were measured using electrochemiluminescence immunoassays in Abbott Alinity i analyzer. Following the exclusion of outliers, the RIs were determined using three statistical techniques: the non-parametric method, the Hoffmann method, and the Q-Q plot method. Pregnant women's levels of these three thyroid hormones differ markedly from those of healthy non-pregnant women. In addition, the concentrations of these three hormones change considerably over the course of the three phases of pregnancy. The Q-Q plot method offered more comparable RIs with the non-parametric method in healthy non-pregnant women than the Hoffmann method. Three statistical techniques were used to construct the trimester-specific RIs of thyroid hormones in pregnant women, and there was little difference between them all. The RIs by the non-parametric and Q-Q plot methods indicated closer RIs, and the RIs by the Hoffmann approach were higher and wider than those by the other two methods. For thyroid hormones, trimester-specific RIs are required. The RIs determined by non-parametric and Q⁃Q plot indirect calculation could be used as the alternative method.

RIbench: A Proposed Benchmark for the Standardized Evaluation of Indirect Methods for Reference Interval Estimation.

Indirect methods leverage real-world data for the estimation of reference intervals. These constitute an active field of research, and several methods have been developed recently. So far, no standardized tool for evaluation and comparison of indirect methods exists. We provide RIbench, a benchmarking suite for quantitative evaluation of any existing or novel indirect method. The benchmark contains simulated test sets for 10 biomarkers mimicking routine measurements of a mixed distribution of non-pathological (reference) values and pathological values. The non-pathological distributions represent 4 common distribution types: normal, skewed, heavily skewed, and skewed-and-shifted. To identify strengths and weaknesses of indirect methods, test sets have varying sample sizes and pathological distributions differ in location, extent of overlap, and fraction. For performance evaluation, we use an overall benchmark score and sub-scores derived from absolute z-score deviations between estimated and true reference limits. We illustrate the application of RIbench by evaluating and comparing the Hoffmann method and 4 modern indirect methods -TML (Truncated-Maximum-Likelihood), kosmic, TMC (Truncated-Minimum-Chi-Square), and refineR- against one another and against a nonparametric direct method (n = 120). For the modern indirect methods, pathological fraction and sample size had a strong influence on the results: With a pathological fraction up to 20% and a minimum sample size of 5000, most methods achieved results comparable or superior to the direct method. We present RIbench, an open-source R-package, for the systematic evaluation of existing and novel indirect methods. RIbench can serve as a tool for enhancement of indirect methods, improving the estimation of reference intervals.

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

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. 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. 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. 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.

Verifying Clinically Derived Reference Intervals for Daily Excretion Rates of Fractionated Metanephrines Using Modern Indirect Reference Interval Models.

Biochemical testing of urinary metanephrines is useful in the diagnosis and monitoring of pheochromocytoma and paragangliomas. We investigated the feasibility of mixture decomposition (ie, indirect) methods in verifying clinically derived reference intervals for urinary deconjugated metanephrine metabolites. Urinary 24-hour metanephrine and normetanephrine excretion results were extracted from our data warehouse and intervals were estimated by the modern variant of the Hoffmann method, maximum likelihood estimation (MLE), and gamma mixture model using R software. Hoffmann, MLE, and gamma mixture models provided metanephrine and normetanephrine intervals that closely matched those derived from clinical studies. However, three-component MLE and gamma models were required for normetanephrine in adult women because the Hoffmann method was not suitable. Some data transformations caused blending of the mixed distributions and subsequent widening of the reference interval estimation, emphasizing the importance of careful data transformation for Hoffmann and MLE analyses. Gamma mixture models gave overall good agreement without the need for data transformation. Indirect methods have utility in verifying reference intervals in 24-hour urine specimens collected by patients. We emphasize the benefits of applying multiple decomposition methods to corroborate findings and careful application of data transformation when using Gaussian-based models.

Establishing reference ranges of serum lipid level during pregnancy and evaluating its association with perinatal outcomes: A cohort study

To establish trimester-specific reference intervals (TSRIs) for blood lipid profiles in Chinese women and explore their associations with pregnancy outcomes. Participants were singleton pregnant women aged 18-45 years without pre-existing chronic diseases who delivered from January 2018 to December 2018 from an on-going cohort in Beijing, China. Baseline information and pregnancy outcomes were from the medical records. Blood lipid levels were measured at 7-13 weeks, 24-28 weeks, and 32-34w weeks of gestation. We estimated TSRIs for lipid profiles using an indirect Hoffmann method and evaluated their associations with pregnancy outcomes, including gestational diabetes, pregnancy-induced hypertension, macrosomia, low birth weight, large or small for gestational age, and preterm delivery. The established TSRIs were 3.21-5.38 mmol/L, 4.64-7.56 mmol/L, and 4.86-8.20 mmol/L for total cholesterol; 0.37-1.81 mmol/L, 1.14-3.49 mmol/L, and 1.61-4.63 mmol/L for triglycerides; 1.12-2.19 mmol/L, 1.33-2.49 mmol/L, and 1.24-2.31 mmol/L for high density lipoprotein cholesterol; 1.33-2.98 mmol/L,1.97-4.36 mmol/L, and 2.02-4.92 mmol/L for low density lipoprotein cholesterol from T1 to T3, respectively. Both higher and lower levels of lipid profiles than TSRIs were associated with adverse pregnancy outcomes. We suggested TSRIs for blood lipid levels in a Chinese population. Inappropriate lipid levels were associated with adverse pregnancy outcomes.

Establishment of trimester-specific reference intervals of serum lipids and the associations with pregnancy complications and adverse perinatal outcomes: a population-based prospective study

Background Disturbances in maternal lipid metabolism may increase the risk of developing pregnancy complications and adverse perinatal outcomes. However, there is no consensus as to what constitutes normal serum lipid ranges during pregnancy. Our study was aimed to establish trimester-specific serum lipid reference intervals (RIs) and investigate the associations between maternal dyslipidaemia and adverse outcomes in a population-based study. Methods The first- and third-trimester lipid profiles were derived from 16,489 singlet pregnant women for regular antenatal check-ups between 2017 and 2019. The serum samples were assayed for total cholesterol (TC), triglycerides (TG), high-density lipoprotein-cholesterol (HDL-C), and low-density lipoprotein-cholesterol (LDL-C) in the institutional clinical laboratory. The trimester-specific lipid RIs were estimated with both of the direct observational and the indirect Hoffmann methods. The associations between maternal lipid profiling and pregnancy complications and perinatal outcomes were assessed statistically. Results Serum levels of TC, TG, LDL-C and HDL-C were all increased significantly in the third trimester of pregnancy. There was no significant difference between the observed RIs established with healthy pregnant women and the calculated RIs derived from the Hoffmann method. A trend towards increased risks of gestational complications and adverse perinatal outcomes was observed in the subjects with elevated levels of TC, TG, and LDL-C or decreased level of HDL-C. Conclusions In pregnancy, increased serum levels of TC, TG and LDL-C, and a decreased level of HDL-C posed higher risks of developing pregnancy complications and adverse perinatal outcomes. Key messages It is necessary to establish trimester-specific reference intervals for serum lipids including TC, TG, LDL-C and HDL-C that were found significantly increased as the gestational age went up. More importantly, around the upper reference limits of TC, TG and LDL-C (or the lower reference limit of HDL-C), the higher the serum lipid levels were (or the lower the HDL-C level was), the higher risks of developing pregnancy complications and adverse perinatal outcomes were observed.

Egg quality and endoparasite prevalence in free range chicken farming in Apodi and Mossoró, Rio Grande do Norte, Brazil

The objective of this work was to assess the production quality of free-range eggs in the municipalities of Apodi and Mossoró, in the state of Rio Grande do Norte, Brazil. The microbiological and physical quality of the eggs and the endoparasite prevalence in the chickens were used as parameters. The egg microbiological evaluation consisted of the detection and quantification of total and thermotolerant coliforms, mesophilic bacteria, Staphylococcus aureus, and Salmonella sp. The eggs were classified according to their weight, yolk color, yolk pH, albumen pH, Haugh unit, yolk index, and shell thickness. The parasitological analyses consisted of collection of fresh excreta and application of the spontaneous sedimentation technique by the Hoffmann method and the Faust flotation method to identify the parasites. All egg samples were negative for total and thermotolerant coliforms, mesophilic bacteria, and Salmonella sp. Regarding the physical quality, the eggs presented good yolk pigmentation and good internal and external quality. Regarding the parasitic load of the chickens, the presence of Eimeria sp. and Heterakis sp. was significantly higher in months with average precipitation greater than 100 mm; and in months with average relative air humidity above 80%, there was prevalence of Ascaris sp. parasites.

Retinol and α-tocopherol in pregnancy: Establishment of reference intervals and associations with CBC.

Profound physiological changes during pregnancy may affect the requirement of retinol and tocopherol, which are essential micronutrients for the maintenance of maternal health and foetal development. However, the current reference intervals (RIs) of retinol and tocopherol are based on non‐pregnant population. In the present study, a liquid chromatography–tandem mass spectrometry quantitation method for serum retinol and α‐tocopherol was established and validated. In addition, we established trimester‐specific RIs of retinol and α‐tocopherol using the data from paired screening test for 31,301 outpatients who participated in the prenatal vitamins A/E evaluation program at our hospital using the Hoffmann method, which is a simple indirect RI estimation method that does not require the recruitment of healthy subjects. Further, to explore the associations between the levels of retinol and α‐tocopherol and the parameters of complete blood count (CBC), the results of retinol, α‐tocopherol, and CBC of 1,977 pregnant outpatients in the third trimester were analysed. The testing interval between the levels of vitamins and CBC was no more than 7 days. Although no significant changes were noticed in the levels of retinol, the α‐tocopherol levels continuously increased with normal physiological changes throughout pregnancy. Lower retinol levels were associated with the higher incidence of anaemia, whereas higher levels of retinol and lower levels of α‐tocopherol were associated with higher platelet count.

Widespread Incorrect Implementation of the Hoffmann Method, the Correct Approach, and Modern Alternatives.

The Hoffmann method is a procedure for reference interval estimation using routine clinical results. Many authors incorrectly prepare Hoffmann plots on a linear rather than normal probability scale. We explore the consequences. This was investigated algebraically, by random number simulations (45 simulations, n = 100,000 each) and using clinical data sets. Strategies compared were: Hoffmann's method as originally and incorrectly implemented, Bhattacharya's method, and maximum likelihood (ML). All R source code and data sets are provided. As the proportion of healthy individuals approaches 1, the incorrect approach generates reference interval estimates of approximately μH ± 1.19 σH delineating the central 77% of the healthy subpopulation, not the central 95%. Inappropriately narrow reference interval estimates were seen on random simulations and clinical data sets. ML methods performed best. The erroneous variant Hoffmann method should not be used. ML methods outperform others and are not restricted by Gaussian assumptions.

Limitations of the Hoffmann method for establishing reference intervals using clinical laboratory data

ObjectiveTo examine the effect of different limits of acceptability on the Hoffmann method for selecting “healthy” populations from laboratory test data. MethodsThyroid stimulating hormone (TSH) and free thyroxine (FT4) were measured in Shunyi Maternal and Children's Hospital of Beijing Children's Hospital. The sample size of participants of TSH and FT4 for reference intervals (RIs) establishment was 10,864 and 10,799, respectively. RIs were calculated by Hoffmann method with different acceptable deviations (α value). The validation data was collected prospectively and the out-of-range (OOR) values were calculated to examine the applicability of RIs with different acceptable deviations. The sample size for RIs validation was 880 and 867, respectively. The RIs were considered as valid when OOR was <10%. Resultsα value was set at different levels for establishing the RIs of TSH and FT4. It was shown that the larger α value, the wider the RI. The RIs calculated by the Hoffmann method, under the default α value of 0.05, were much narrower than the previous findings. The OOR of both TSH and FT4 were far more from 10% when the α value was 0.05. In this simulation, the OOR of TSH and FT4 was not <10% until the α value was set as 0.55 and 0.80, respectively. The established RIs were valid for both training dataset and validation dataset. ConclusionsIt can be somewhat subjective to define the acceptable deviation when selecting “normal” reference individuals. The default value of acceptable deviation may not be applicable in some cases. It is necessary to determine the acceptable deviation based on the certain condition, instead of using the default value directly.

Reference intervals of trimester-specific thyroid stimulating hormone and free thyroxine in Chinese women established by experimental and statistical methods.

As a result of physiological and metabolic changes during pregnancy, thyroid hormones can be affected significantly throughout entire three trimesters. According to the guidelines published by American Thyroid Association in 2017, it is strongly recommended to establish population-based trimester-specific and assay method-specific reference intervals (RIs) using local population. A total of 1209 pregnant women without personal or family history of thyroid disease were recruited from July 2015 to April 2017 at Beijing Obstetrics and Gynecology Hospital. Those initially selected patients were further tested for TSH, FT4 and thyroid peroxidase antibody (aTPO), performed on the chemiluminescent platform Siemens ADVIA Centaur® XP. Only patients tested negative for aTPO were included in reference interval establishment. RIs for both TSH and FT4 were determined as 2.5th percentile to 97.5th percentile on the data distribution. The TSH and FT4 trimester-specific RIs were as follows: 0.59-3.54 mIU/L, 11.8-18.4 pmol/L (n=188, 1st trimester); 0.80-4.46 mIU/L, 11.6-17.4 pmol/L (n=133, 2nd trimester); 0.72-4.19 mIU/L, 9.7-15.1 pmol/L (n=157, 3rd trimester). The RIs of TSH and FT4 determined by Hoffmann method for first trimester outpatient pregnant women were 0.33-3.96 mIU/L (n=9924) and 11.7-17.5 pmol/L (n=10039), respectively. Trimester-specific thyroid function tests RIs are distinct from those provided by assay manufacturers. The RIs determined by direct sampling and Hoffmann indirect calculation showed no statistical difference.

The Reference Intervals Used in Pediatric Medical Analysis Laboratories to Interpret the Results Analysis for Total Serum Calcium

Medical analysis laboratory must establish its own reference intervals depending on the facilities they are working with, the working substances and protocols. These reference intervals must be obtained depending on age groups in order to accurately interpret the results of the analyzes performed. The study is a retrospective one using 3217 data from the electronic archive of the S.C. Vladutiu&amp;Garabedian S.R.L. Clinic in Medias. Total serum calcium was determined by the colorimetric method on the Konelab analyzer. Processing of the collected data was done using the Hoffmann method, considering 5% up to 95% of the values in the database, the values being randomly selected. For comparison, data from the literature was used. In children under 1 year old, it was not possible to calculate the reference intervals since data was insufficient. In the other age groups, reference intervals obtained in the current study were similar to the studied literature. Reference intervals established for calcium can provide important guidance for the reasonable supplementation of this essential element in children.

Establishing reference intervals of the routine laboratory tests for hepatorenal function in Shanghai by biochemistry

Objective To establish reference intervals of nine laboratory projects for hepatorenal function and verify its reliability by indirect method. Methods ALL test results were extracted from physical examinations that were stored in the laboratory information system of Zhongshan Hospital during 2012 to 2014. Using Skewness-Kurtosis test to detect the normality of data, if not the original data were transformed through BOX-COX transformation to obtain an approximatenormal distribution. Outliers were identified and omitted by Turkey method. The indirect reference intervals were taken by applying Hoffmann method. The reference change value (RCV) was selected to inspect the statistical significance between the calculated and published reference intervals. Results Among those nine laboratory projects, thedifferences betweenthereference intervalsfor ALT, AST, AKP, GGT, TP, BUNwerelessthan their RCV( 26.65%, 9.92%) , and there was a significant difference between the calculated reference intervals and the current reference interval in the laboratory for the lower limit of the UA of male(>26.65%). Conclusion This research further proved the reliability of indirect reference intervals and this technique deserved to be promoted and applied by other clinical laboratories.(Chin J Lab Med, 2016, 39: 906-910) Key words: Liver function tests; Kidney function tests; Reference values