Insulin reference intervals in Brazilian adolescents by direct and indirect approaches: validation of a data mining method from laboratory data

Abstract Objective To determine reference intervals (RI) for fasting blood insulin (FBI) in Brazilian adolescents, 12 to 17 years old, by direct and indirect approaches, and to validate indirectly determined RI. Methods Two databases were used for RI determination. Database 1 (DB1), used to obtain RI through a posteriori direct method, consisted of prospectively selected healthy individuals. Database 2 (DB2) was retrospectively mined from an outpatient laboratory information system (LIS) used for the indirect method (Bhattacharya method). Results From DB1, 29345 individuals were enrolled (57.65 % female) and seven age ranges and sex partitions were statistically determined according to mean FBI values: females: 12 and 13 years-old, 14 years-old, 15 years-old, 16 and 17 years-old; and males: 12, 13 and 14 years-old, 15 years-old, 16 and 17 years-old. From DB2, 5465 adolescents (67.5 % female) were selected and grouped according to DB1 partitions. The mean FBI level was significantly higher in DB2, on all groups. The RI upper limit (URL) determined by Bhattacharya method was slightly lower than the 90 % CI URL directly obtained on DB1, except for group female 12 and 13 years old. High agreement rates for diagnosing elevated FBI in all groups on DB1 validated indirect RI presented. Conclusion The present study demonstrates that Bhattacharya indirect method to determine FBI RI in adolescents can overcome some of the difficulties and challenges of the direct approach.

Detección de macroenzimas después de la precipitación con polietilenglicol: búsqueda de la población de referencia en el caso particular de las aminotransferasas / Detection of macroenzymes for aminotransferases after polyethylene glycol precipitation: search for the reference population / Detecção de macroenzimas após a precipitação com polietilenoglicol: busca da população de referência no caso particular das aminotransferases

Resumen Las macroenzimas son complejos de elevado peso molecular que podrían incrementar la actividad enzimática sérica en ausencia de signos y síntomas. Se pueden detectar al ser precipitadas con polietilenglicol. El objetivo del trabajo fue determinar la actividad de las aminotransferasas por el método IFCC, calcular y comparar la media del porcentaje de actividad precipitable (x̄), su intervalo de confianza del 95% (IC95%) y el desvío estándar (DE). Se trabajó con individuos con (n=42) y sin hipertransaminasemia (n=22). Los resultados para uno y otro fueron: porcentaje de actividad precipitable con polietilenglicol (%PPA) (x̄, DE, IC95%) = (28%; 1,82; 27,45%-28,55% y 44%; 24,52; 32,84%-55,16%) y (15%; 13,03; 11,01%-18,99% y 25%; 9,1; 20,96%-29,04%) para ALT y AST, respectivamente (p=0,003 y p=0,001; p<0,05). En conclusión, la estimación de la media poblacional podría ser más precisa en individuos con hipertransaminasemia.

Abstract Macroenzymes are high-molecular-mass complexes that might increase the serum enzymatic activity in the absence of symptoms. An easy-touse method to detect them is the polyethylene glycol precipitation. The aim of this study was to determine aminotransferases activity using the IFCC method, and to calculate the mean percentage of precipitable activity (x̄), its 95% confidence interval (CI95%), and the standard deviation (SD). The study included individuals with (n=42) and without hypertransaminasemia (n=22). The results were: percentaje of precipitable activity (%PPA) (x̄, SD, CI95%) = (28%; 1.82; 27.45%-28.55% and 44%; 24.52; 32.84%-55.16%) and (15%; 13.03; 11.01%-18.99% and 25%; 9.1; 20.96%-29.04%) for ALT and AST, respectively (p=0.003 and p=0.001; p<0.05). In conclusion, the estimation of the population mean could be more precise in individuals with hypertransaminasemia.

Resumo As macroenzimas são complexos de alto peso molecular que poderiam aumentar a atividade enzimática sérica na ausência de sinais e sintomas. Podem ser detectadas ao precipitar com polietilenoglicol. O objetivo do trabalho foi determinar a atividade das aminotransferases pelo método IFCC, calcular e comparar a média da porcentagem de atividade precipitável (x̄), seu intervalo de confiança de 95% (IC95%) e o desvio padrão (DP). O trabalho foi realizado com indivíduos com (n=42) e sem hipertransaminasemia (n=22). Os resultados para os dois foram: porcentagem de atividade precipitável com polietilenoglicol (%PPA) (x̄, DP, IC95%)=(28%; 1,82; 27,45%- 28,55% e 44%; 24,52; 32,84%- 55,16%) e (15%; 13,03; 11,01%-18,99% e 25%; 9,1; 20,96%-29,04%) para ALT e AST, respectivamente (p=0,003 e p=0,001; p<0,05). Concluindo, a estimativa da média populacional poderia ser mais precisa em indivíduos com hipertransaminasemia.

Análisis de los niveles de ácidos orgánicos en orina de la primera infancia y recién nacidos: un estudio de cromatografía gaseosa acoplada a espectrometría de masas con evaluación de rangos de referencia / Analysis of urinary organic acid levels in early childhood and newborns: a gas chromatography-mass spectrometry study with evaluation of reference ranges / Análise dos níveis de ácidos orgânicos na urina da primeira infância e dos recém-nascidos: um estudo por cromatografia gasosa acoplada a espectrometria de massa com avaliação de intervalos de referência

Resumen El análisis de los ácidos orgánicos urinarios juega un papel crucial en el diagnóstico y seguimiento de pacientes con trastornos metabólicos congénitos. La falta de datos completos, las variaciones en los hábitos alimentarios entre países y el aumento del consumo de alimentos procesados subrayan la necesidad de realizar investigaciones actualizadas. Con el fin de establecer los intervalos de confianza y medianas de ácidos orgánicos urinarios se evaluaron mediante cromatografía gaseosa acoplada a espectrometría de masas, 125 muestras de orina de pacientes sanos, con edades comprendidas entre 2 días y 13 años. Los resultados fueron analizados teniendo en cuenta el grupo etario, y evidenciaron que las concentraciones de la mayoría de los ácidos orgánicos urinarios varían de acuerdo a la edad, lo que enfatiza la importancia de los valores de referencia emparejados con la edad para interpretar los datos de los pacientes. Existen pocos informes en esta área; sin embargo, la comparación de estos resultados con los valores de referencia informados por otros trabajos muestra una concordancia razonable y las pocas disparidades podrían atribuirse a factores genéticos o influencias dietéticas. Se presentan resultados e interpretaciones de niños previamente diagnosticados con trastornos metabólicos y otras afecciones, lo que confirma la confiabilidad de nuestros datos y métodos analíticos. Este estudio proporciona datos de referencia esenciales para los profesionales clínicos, destaca la importancia de los valores de referencia específicos de la edad para diagnosticar y tratar con precisión a pacientes con trastornos metabólicos y sirve como recurso fundamental para futuras investigaciones en este campo.

Abstract Analysis of urinary organic acids plays a crucial role in the diagnosis and monitoring of patients with congenital metabolic disorders. The lack of complete data, variations in dietary habits between countries, and increasing consumption of processed foods highlight the need for up-to-date research. In order to establish the confidence intervals and medians of urinary organic acids, 125 urine samples from healthy patients, aged between 2 days and 13 years, were evaluated by gas chromatography coupled to mass spectrometry. The results were analysed taking into account the age group, showing that the concentrations of most urinary organic acids vary according to age, which emphasises the importance of paired age reference values to interpret patient data. There are few reports in this area; however, comparing our results with those reference values reported by other papers demonstrates reasonable agreement, and minor disparities could be attributed to genetic factors or dietary influences. Results and interpretations from children previously diagnosed with metabolic disorders and other conditions are presented, confirming the reliability of our data and analytical methods. This study provides essential reference data for clinicians, highlighting the importance of age-specific reference values to accurately diagnose and treat patients with metabolic disorders and serves as a critical resource for future research in this field.

Resumo A análise dos ácidos orgânicos urinários desempenha um papel crucial no diagnóstico e monitoramento de pacientes com distúrbios metabólicos congênitos. A falta de dados completos, as variações nos hábitos alimentares entre países e o aumento do consumo de alimentos processados destacam a necessidade de realizar pesquisas atualizadas. Para estabelecer os intervalos de confiança e medianas de ácidos orgânicos urinários, 125 amostras de urina de pacientes saudáveis, com idades entre 2 dias e 13 anos, foram avaliadas por cromatografia gasosa acoplada à espectrometria de massa. Os resultados foram analisados levando em consideração o grupo etário, evidenciando que as concentrações da maioria dos ácidos orgânicos urinários variam de acordo com a idade, o que destaca a importância dos valores de referência pareados com a idade para interpretar os dados dos pacientes. Há poucos relatos nesta área; no entanto, a comparação destes resultados com os valores de referência informados por outros trabalhos demonstra uma concordância razoável, e as poucas disparidades poderiam ser atribuídas a fatores genéticos ou influências dietéticas. São apresentados resultados e interpretações de crianças previamente diagnosticadas com distúrbios metabólicos e outras condições, o que confirma a confiabilidade de nossos dados e métodos analíticos. Este estudo fornece dados de referência essenciais para profissionais clínicos, enfatizando a importância dos valores de referência específicos da idade para diagnosticar e tratar com precisão pacientes com distúrbios metabólicos, e serve como recurso fundamental para futuras pesquisas nesse campo.

Establishment of age-specific reference intervals for AMH in Indian women and enhancing its use as a diagnostic marker in PCOS

Background: Anti Mullerian hormone (AMH) level is a reliable marker of ovarian reserve. It is known to be influenced by factors like age, ethnicity, and ovarian pathology. Establishment of age-specific reference intervals for AMH, characteristic of different nationalities, is therefore of utmost importance. Serum AMH is known to be elevated in women with polycystic ovarian syndrome (PCOS). It is desirable to determine a population-specific cut-off of AMH, for it to be used as a diagnostic marker for PCOS.Methods: Serum AMH, luteinizing hormone (LH), follicle-stimulating hormone (FSH), Estradiol, Progesterone and Testosterone assays were analyzed in 1978 Indian women, in the age range of 12–50 years. Age-specific reference intervals for AMH were derived for the study population. The cohort of study subjects were then divided into two groups, based on AMH values and clinical history: Control group, and patients with PCOS. The cut-off value of AMH in the study population, corresponding to the diagnosis of PCOS, was also established. Results: Upper 95th percentile limits of reference intervals for the 18-25 26–30, 31–35, and 36–40, 41-45 and >45 age groups were 9.69, 7.60, 6.50, 6.1, 4.80 and 4.5 ng/ml respectively. In the PCOS group the 5th percentile value was 7.80 ng/ml and the upper 95th percentile was 21.81 ng/ml. The median percentile in PCOS group was 10.40 ng/ml. ROC analysis was done to obtain optimal cutoff values for each age group with better discriminative power than the reference limits. The best cut-off point of AMH value for PCOS in our study population was 7.51ng/ml. The sensitivity and specificity were 99.4% and 95.5%, respectively. The calculated area under the Receiver operating characteristic (ROC) curve was 0.988 (95% CI: 0.984-0.991, P <0.001). AMH, LH, and LH/FSH ratio was significantly higher in the PCOS group than in the control group (p < 0.001 for all comparisons). LH/FSH ratio was more than 2 in the PCOS group compared to controls. Serum Testosterone was significantly higher in PCOS.Conclusions: The study aids to establish a biological reference interval for AMH, specific for different age groups in Indian women. 7.51ng/ml has been derived as a diagnostic cut-off of AMH for PCOS in our study population. The establishment of age-specific reference intervals, and syndrome-specific cut-offs in the Indian population will help overcome the influence of variables and broaden the use of AMH in women’s health.

Establishment of age-specific reference intervals for AMH in Indian women and enhancing its use as a diagnostic marker in PCOS

Background: Anti Mullerian hormone (AMH) level is a reliable marker of ovarian reserve. It is known to be influenced by factors like age, ethnicity, and ovarian pathology. Establishment of age-specific reference intervals for AMH, characteristic of different nationalities, is therefore of utmost importance. Serum AMH is known to be elevated in women with polycystic ovarian syndrome (PCOS). It is desirable to determine a population-specific cut-off of AMH, for it to be used as a diagnostic marker for PCOS.Methods: Serum AMH, luteinizing hormone (LH), follicle-stimulating hormone (FSH), Estradiol, Progesterone and Testosterone assays were analyzed in 1978 Indian women, in the age range of 12–50 years. Age-specific reference intervals for AMH were derived for the study population. The cohort of study subjects were then divided into two groups, based on AMH values and clinical history: Control group, and patients with PCOS. The cut-off value of AMH in the study population, corresponding to the diagnosis of PCOS, was also established. Results: Upper 95th percentile limits of reference intervals for the 18-25 26–30, 31–35, and 36–40, 41-45 and >45 age groups were 9.69, 7.60, 6.50, 6.1, 4.80 and 4.5 ng/ml respectively. In the PCOS group the 5th percentile value was 7.80 ng/ml and the upper 95th percentile was 21.81 ng/ml. The median percentile in PCOS group was 10.40 ng/ml. ROC analysis was done to obtain optimal cutoff values for each age group with better discriminative power than the reference limits. The best cut-off point of AMH value for PCOS in our study population was 7.51ng/ml. The sensitivity and specificity were 99.4% and 95.5%, respectively. The calculated area under the Receiver operating characteristic (ROC) curve was 0.988 (95% CI: 0.984-0.991, P <0.001). AMH, LH, and LH/FSH ratio was significantly higher in the PCOS group than in the control group (p < 0.001 for all comparisons). LH/FSH ratio was more than 2 in the PCOS group compared to controls. Serum Testosterone was significantly higher in PCOS.Conclusions: The study aids to establish a biological reference interval for AMH, specific for different age groups in Indian women. 7.51ng/ml has been derived as a diagnostic cut-off of AMH for PCOS in our study population. The establishment of age-specific reference intervals, and syndrome-specific cut-offs in the Indian population will help overcome the influence of variables and broaden the use of AMH in women’s health.

Establishment of reference intervals of squamous cell carcinoma antigen for healthy population in Nanning region / 基础医学与临床

Objective To establish a reference intervals(RIs)of serum squamous cell carcinoma antigen(SCC-Ag)in healthy population in Nanning region and provide clinical evidence to support diagnosis and prognosis of squamous cell carcinoma.Methods A total of 10 197 reference individuals who joined a routine physical examina-tion in the Health Management Center of Guangxi International Zhuang Medical Hospital from March 2019 to De-cember 2021 were collected.The level of serum SCC-Ag was detected by chemiluminescence microparticle immuno-assay.The Mann-Whitney U test was applied to compare the differences in serum SCC level between genders or ad-jacent age groups.The unilateral 95th percentile determined the upper limit of the RIs by the nonparametric method.Another 1 035 healthy subjects with the same conditions as the reference population were selected for refer-ence validation.Results The serum SCC-Ag level showed a skewed distribution(Z＝0.08,P＜0.05).The ser-um SCC-Ag level of males was considerably higher than that of females.There was significant difference in serum SCC-Ag level between males aged 18－30 and 31－40,51－60 and 61－90(P＜0.05).There was significant difference in serum SCC-Ag level between females aged 18－30 and 31－40,31－40 and 41－50,51－60 and 61－ 90(P＜0.05).The reference intervals of serum SCC-Ag was as follows:0－1.64 ng/mL for males and females aged 18－30 years;0－1.57 ng/mL and 0－1.70 ng/mL for males aged 31－60 years and 61－90 years,respec-tively;0－1.50 ng/mL,0－1.52 ng/mL and 0－1.42 ng/mL for females aged 31－40 years,41－60 years and 61－90 years,respectively.Conclusions The RIs of serum SCC-Ag in healthy population in the Nanning region are successfully established according to different genders and ages.

Necessity and methodological progress on the establishment of continuous reference intervals for pediatric age-dependent indicators / 中华检验医学杂志

Accurate and applicable reference intervals can provide important information for disease diagnosis, efficacy evaluation, and health monitoring. Age-dependent trends exist for many clinical laboratory indicators, and the interpretation of such indicators should consider the effect of age carefully. However, age-specific reference intervals have certain limitations in clinical application. Continuous reference intervals can not only help accurate interpretation of laboratory test results, but also provide a baseline value for dynamic monitoring of their changing trends. Based on the researches on pediatric reference intervals from our team, this paper introduces different algorithms for establishing continuous reference intervals, and their applicable conditions and implementation steps. The aim of this paper is to provide methodological guidance for the establishment of continuous reference intervals, so as to improve the quality of laboratory reports and the accuracy of clinical diagnosis in China.

Intraocular pressure distribution and reference interval of high-altitude eye health screening population from Xining, Qinghai / 中华实验眼科杂志

Objective:To investigate the distribution of intraocular pressure (IOP) in high-altitude population aged 18 years and over in Xining, Qinghai and establish the reference interval (RI) of IOP.Methods:A cross-sectional study was conducted in Xining, Qinghai Province at 2.271 km above sea level from September 2019 to May 2020.Ophthalmic examinations and IOP measurement were conducted among subjects from Physical Examination Center of Qinghai Provincial People's Hospital.The subjects who had been living in Xining without leaving for three months were enrolled.Ophthalmic examinations included vision examination, IOP measurement, slit-lamp microscopy, fundus photography, anterior and posterior segment optical coherence tomography.IOP was measured using Goldmann applanation tonometry under local anesthesia.Subjects with factors that could cause significant changes in IOP and affect the accuracy of IOP measurement, and those who were unable to receive IOP measurement were excluded.Subjects were grouped according to sex, age and ethnicity, and the distribution and RI of IOP were compared among all groups.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Beijing Tongren Hospital, Capital Medical University (No.TRECKY2017-024). Written informed consent was obtained from each subject.Results:A total of 6 120 subjects (6 120 eyes) aged 18-90 years old were enrolled, including 2 850 males and 3 270 females with average age of (45.54±13.85) years.The average IOP of high-altitude population in Xining, Qinghai Province was (14.32±1.93) mmHg (1 mmHg=0.133 kPa), with the RI of 10.54-18.10 mmHg.The average IOP was (14.42±1.98) mmHg in male with the RI of 10.54-18.30 mmHg, (14.23±1.88) mmHg in female with the RI of 10.55-17.91 mmHg.The IOP of male was higher than that of female ( t=3.71, P<0.001). The IOP of Han, Tibetan, Hui and other nationalities were (14.38±1.91), (13.93±2.06), (14.21±1.87), (13.94±1.95) mmHg, respectively, with a statistically significant overall difference ( F=6.73, P<0.001). The IOP of Han nationality was significantly higher than that of Tibetan, Hui and other nationalities, and the differences were statistically significant (all at P<0.05). Conclusions:RI of IOP in high-altitude population from Xining, Qinghai is lower compared with normal altitude area.

Results of Determination of Mean Values and Reference Intervals for Some Vitamins / Монголын Анагаах Ухаан

Background@#Vitamins are nutrients essential for human health. They act as coenzymes that help trigger important chemical reactions necessary for energy production. Reference values for vitamins help physicians evaluate the health status of patients and make clinical decisions. The aim of this study was to determine the mean values and reference intervals for some water-soluble vitamins of Mongolian adults.@*Materials and Methods@#Three hundred and forty healthy adults (170 males and 170 females) of 17 to 69 years of age were selected for the study based on CLSI C28-P3 criteria Defining, establishing & Verifying reference interval in the clinical laboratory; Proposed Guidelines. The study was approved by the Resolution No.76 of 2018 of the Medical Ethics Review Committee of the Ministry of Health. Informed consents were taken from the selected individuals. Morning blood samples of the participants were collected under aseptic conditions. Levels of vitamins B₆, B₉, B₁₂ and vitamin C were measured using a high performance liquid chromatography method. The lower- and upper reference limits were defined as the 2.5th and 97.5th percentiles, respectively. The data were analyzed using SPSS and Excel programs.@*Results@#The mean blood level of vitamin C was 11.88 mg/L (95% CI 10.47-13.29) for men and 9.62 mg/L (95% CI 8.11-11.13) for women. The calculated reference interval for males was 1.40-19.40 mg/L and 1.17-18.04 mg/L for females. The mean concentration of vitamin B₁₂ in the blood of males was 938.45 ng/L (95% CI 747.22-1129.68) and that of females was 864.03 ng/L (95% CI 603.81-1124.25). The reference interval for vitamin B₁₂ was 233.03-1597.00 ng/L in men and 132.45-1623.86 ng/L in women. The mean level of vitamin B₉ was 8.47 ng/mL (95% CI 5.64-11.30) for men and 6.91 ng/mL (95% CI 4.89-8.93) for women. The calculated reference interval for this vitamin in males was 1.04-24.74 ng/mL and that in females was 1.04-21.46 ng/mL. As for vitamin B₆, the mean concentration for men was 44.42 ng/mL (95% CI 37.01-51.83) and for women was 34.67 ng/mL (95% CI 29.97-39.39) with the reference intervals of 5.90-79.02 ng/mL for men and 5.27-61.72 ng/mL for women. @*Conclusion@#The reference values for vitamins B₆, B₉, B₁₂ and vitamin C of Mongolian adults do not differ significantly from those observed in other populations. The calculated reference intervals can be used in the practice of health laboratories.

Establishment and validation of reference interval of D-dimer in plasma of healthy pregnant women in Xi ′an / 中华检验医学杂志

Objective:To provide normal reference thresholds for clinical dynamic monitoring of the risk of microthrombus during pregnancy, we aimed to establish reference intervals of D-dimer in healthy pregnant women during different periods of gestation in Xi′an.Method:From December 2020 to March 2022, a total of 1502 healthy pregnant women and healthy non-pregnant women (healthy non-pregnant control group) who received routine prenatal examination in Northwest Women and Children′s Hospital were recruited in the study by questionnaire, including 1236 healthy pregnant women and 266 healthy non-pregnant control group. Plasma D-dimer concentration was detected by STA-R Evolution automatic blood coagulation analyzer and the concentration levels of D-dimer in different pregnancies and age groups were calculated using Graph Prism 9.0 software. In addition, 20 samples were collected in each pregnancy to verify the established reference interval.Results:There was no significant difference in plasma D-dimer levels between<30 years old and ≥30 years old at different gestational weeks. Plasma D-dimer level in healthy pregnant women group was significantly higher than that in healthy non-pregnant women group of the same age (P<0.05). With the increase of gestational week, plasma D-dimer level in pregnant women increased significantly, and plasma D-dimer level at different gestational weeks ≤13 weeks, 13+ 1-20 weeks, 20+ 1-27 weeks, 27+ 1-35 weeks, ≥35 +1 week were 0.33 (0.26, 0.47) μg/ml, 0.41 (0.30, 0.51) μg/ml, 0.71 (0.48, 0.94) μg/ml, 0.91 (0.70, 1.27) μg/ml, 1.30 (0.96, 1.72) μg/mlrespectively. Unilateral reference interval acuities were≤0.89 μg/ml, ≤1.53 μg/ml, ≤2.44 μg/ml, ≤2.74 μg/ml, ≤3.82 μg/ml respectively. The reference range established in this study was verified by 20 independent samples from each of the 5 gestational age groups, and the results were acceptable. Conclusion:This study preliminarily established the reference interval of plasma D-dimer in healthy pregnant women at different gestational weeks in Xi ′an area, which is helpful for the auxiliary diagnosis of thrombotic diseases during pregnancy.

Establishment of Thromboelastography reference interval for healthy adults in Hainan / 中国输血杂志

【Objective】 To establish the reference interval of Thromboelastography(TEG)of healthy adult in Hainan, compare with the interval provided by the manufacturers, and analyze the influencing factors. 【Methods】 A total of 308 healthy adult volunteers were included according to the inclusion and exclusion criteria. The TEG was analyzed based on adequate quality control, and the reference interval of each parameter was calculated with 95% CI. 【Results】 The reference interval of these volunteers were R 4.27~9.20 min, K 1.60~3.83 min, Angle 44.22°~67.78°, MA 47.82~64.17 mm, CI -5.63~1.12 and G 4.58~9.03. 14.94% (46/308) of these volunteers had at least one index exceeded the reference interval provided by manufacturers. A total of 74 healthy volunteers were diagnosed with coagulation disorder, with the specificity at 79.22%. Significant differences of R, K, Angle, MA, CI, G were observed between males and females (P<0.05). Hypercoagulability was not associated with the age. 【Conclusion】 This study established a reference interval of TEG of healthy adults in Hainan, which provided reference for related clinical and basic science study.

Physiological and hematological parameters of sheep reared in the tropics and subtropics / [Parâmetros fisiológicos e hematológicos de ovinos criados nos trópicos e nos subtrópicos]

This study aimed to determine the physiological and hematological parameters of sheep in Brazil. Therefore, 5,081 observations were used from previous experiments with animals from different Brazilian regions with the time of day, gender, breed, age, physiological characteristics, hematological and climatic variables. The animals were classified according to their stress level, and only data of non-stressed animals were used to calculate the reference values. Respiratory rate was the parameter that most differed from the normal range, with values ​​above the limits usually reported for the species, being higher in commercial wool sheep. For hematological variables, differences were observed between the present results and the previously reported values in the literature. A higher number of red blood cells (RBC), lower hemoglobin and mean corpuscular hemoglobin concentration (MCHC) were observed in young animals. A higher number of RBC and MCHC were noted in sheep crossed with local breeds. Considering that physiological and hematological parameters are indicators of the animal's pathological or physiological state, for a correct interpretation of the results, the use of reference values based on animals with similar racial characteristics and subjected to similar environmental conditions is recommended.(AU)

O objetivo deste estudo foi determinar parâmetros fisiológicos e hematológicos de ovinos no Brasil. Portanto, foram utilizadas 5.081 observações de experimentos anteriores com animais de diversas regiões do Brasil, com diferentes horário, sexo, raça, idade, características fisiológicas, variáveis ​​hematológicas e climáticas. Os animais foram classificados de acordo com o nível de estresse, e apenas os dados dos animais não estressados ​​foram utilizados para o cálculo dos valores de referência. A frequência respiratória foi o parâmetro que mais diferiu em relação à normalidade, com valores acima dos limites usualmente relatados para a espécie, sendo maior em ovinos de lã comercial. Para as variáveis ​​hematológicas, também foram verificadas diferenças entre os resultados observados e os valores previamente relatados na literatura. Maior número de hemácias, menor hemoglobina e concentração de hemoglobina corpuscular média (CHbCM) foram observados em animais jovens e maior número de hemácias e CHbCM em ovinos cruzados com raças locais. Considerando que os parâmetros fisiológicos e hematológicos são indicadores do estado patológico ou fisiológico do animal, para uma correta interpretação dos resultados recomenda-se a utilização de valores de referência baseados em animais com características raciais semelhantes e submetidos a condições ambientais também semelhantes.(AU)

Establishment of reference intervals for thyroid stimulating hormone measurement by big data and indirect method in adults / 中华检验医学杂志

Objective:To establish the sex-, age-and season-specific (month) reference intervals (RI) for thyroid stimulating hormone (TSH) measurement by big data and indirect method in adults.Methods:TSH data of anonymous patients were collected from Beijing Chaoyang Hospital Affiliated to Capital Medical University in 2016, the data were selected and outliers were removed. Indirect methods (Hoffmann method and Bhattacharya method) were used to calculate TSH reference intervals of whole population, different genders, ages and seasons (months). TSH RI from two indirect methods of total population, selected population, physical examination population was compared with RI from reagent instruction according to reference change value ( RCV) based on biological variability. Results:A total of 61 599 records were obtained from 90 699 records including 18 776 males and 42 823 females. The TSH RI were obtained by Hoffmann method: the whole population, 0.59-5.59 μIU/ml (1 μIU/ml=1 mIU/L), male, 0.53-5.16 μIU/ml, female, 0.59-6.11 μIU/ml. The upper limits of TSH RI were higher with age and in winter (January): 18-30 years old, 0.62-5.57 μIU/ml, 71-80 years old, 0.49-6.45 μIU/ml; January, 0.59-6.40 μIU/ml, August, 0.60-5.56 μIU/ml; The RI of TSH by Bhattacharya method: the whole population, 0.58-5.80 μIU/ml, male, 0.55-5.02 μIU/ml, female, 0.62-6.21 μIU/ml. The upper limits of TSH RI were also higher with age and in winter (January): 18-30 years old, 0.65-5.67 μIU/ml, 71-80 years old, 0.46-5.99 μIU/ml, January: 0.61-6.52 μIU/ml, August: 0.61-5.69 μIU/ml. Compared to RI from reagent instruction, the differences of TSH RI from two indirect methods of total population, selected population, physical examination population were acceptable.Conclusions:TSH RI was established by indirect method. With the increase of age and winter, the upper limit of TSH reference interval tends to increase.

Characteristics and reference interval of bile acid profile of healthy pregnant women in second and third trimesters of pregnancy in Zhejiang Province / 中华检验医学杂志

Objective:To investigate the changes and to establish a reference interval of bile acid profile of healthy pregnant women in the second and third trimesters of pregnancy in our hospital.Methods:A total of 298 healthy singleton pregnant women who underwent prenatal examination in the Department of Obstetrics of Zhejiang Provincial People′s Hospital from July 2019 to August 2020 were enrolled in this study. The overnight fasting serum samples were collected from all subjects during their second and third trimesters of pregnancy. The concentrations of 15 bile acids(cholic acid, chenodeoxycholic acid, deoxycholic acid, ursodeoxycholic acid, lithocholic acid and their glycine-and taurine-conjugated types)were analyzed by liquid chromatography tandem mass spectrometry (LC-MS/MS). The characteristics of changes were analyzed and the reference intervals were determined for the second and third trimesters. The concentrations of 15 bile acids and total bile acids were skewed-distributed, and 99 percentiles (P 99) were used to represent the unilateral upper limit of the reference interval. Results:There was significant difference in the serum levels of glycine cholic acid (GCA), taurocholic acid (TCA), glycine ursodeoxycholic acid (GUDCA) and lithocholic acid (LCA) between the second and third trimesters healthy pregnant females ( P<0.05). For other 11 bile acids, there was no significant difference. The levels of total bile acids, primary or secondary bile acids, free or conjugated bile acids (glycine-bound and taurine-bound bile acids) were stable with gestation. Conclusion:Primary, secondary or free, and conjugated bile acids in healthy pregnant women remained stable at T 2 and T 3, with significant differences in only a few subtypes of bile acids. While the correlation between glycine-bound and taurine-bound bile acids showed a weakening trend at T 3 ( P<0.05). It is necessary to establish reference intervals of bile acids for healthy pregnant women in this area. This study provided data support for future research on related diseases during pregnancy.

Relationship between Reference Interval Establishment and Clinical Evaluation in Quantitative / 中国医疗器械杂志

Reference interval study and clinical evaluation are crucial supportive researches to demonstrate the intended use of quantitative

Analysis of Cut Off Value or Reference Interval of / 中国医疗器械杂志

The cut off value or reference interval is significant in clinical testing and diagnosis. If there is no scientific and reasonable cut off value or reference interval for

Changes of serum immunoglobulin level in healthy pregnant women and establishment of its reference interval / 中南大学学报(医学版)

OBJECTIVES@#Pregnant women in a special physiological period, the body's blood indicators will change to a certain extent. This study aims to explore the changes of serum immunoglobulin levels in healthy pregnant women and establish its reference interval (RI).@*METHODS@#A total of 369 healthy pregnant women, who underwent pregnancy examination in the Department of Obstetrics, Second Xiangya Hospital of Central South University from August 2019 to October 2019, were enrolled for this study. They were divided into an early pregnancy group, a middle pregnancy group, and a late pregnancy group according to the pregnancy period, and 123 healthy non-pregnant women were selected as the controls. The levels of immunoglobulin G (IgG), immunoglobulin M (IgM), and immunoglobulin A (IgA) were determined by immune transmission turbidities. The level of immunoglobulin E (IgE) was determined by electrochemiluminescence. The differences in immunoglobulin levels between pregnant women and non-pregnant women and among different gestational periods were analyzed, and the RI of serum immunoglobulin level during pregnancy was established.@*RESULTS@#Compared to the non-pregnant women, the levels of serum IgG, IgM, IgA, and IgE in pregnant women were significantly decreased (all @*CONCLUSIONS@#The levels of immunoglobulin in pregnant women are decreased significantly. The establishment of RIs of IgG, IgM, IgA and IgE in healthy pregnant women could provide scientific basis for clinical decision-making.

Establishment of reference interval for thyroid-stimulating hormone using electrochemiluminescence assay in a healthy adult population from Fortaleza, Brazil

ABSTRACT Objective This study aimed to determine the thyroid-stimulating hormone (TSH) reference interval (RI) and to assess the influence of the use of thyroid ultrasonography (TUS) on reference individual selection from a healthy adult population in Fortaleza, Brazil. Subjects and methods This cross-sectional study recruited patients (N = 272; age = 18-50 years) with normal thyroid function (NTF) and placed them in three groups according to their test results: NTF (n = 272; all participants), TUS (n = 170; participants who underwent thyroid US), RI (n = 124; reference individuals with normal TSH levels). TSH, FT4, TT3, TgAb, and TPOAb concentrations were determined by electrochemiluminescence assay. TUS was performed using a 7-12 MHz multifrequency linear transducer by two radiologists. The 2.5th and 97.5th percentiles of the distribution curve corresponded to lower and upper TSH RI levels, respectively. Results The mean TSH level was 1.74 ± 0.96 mIU/L, and TSH range was 0.56-4.45 mIU/L. There was no difference in the TSH concentrations between men and women nor between the groups. TUS did not appear to be an essential tool for the reference group selection. Conclusion The upper limit of TSH was comparable to the reference interval provided by the assay manufacturer (4.45 vs. 4.20 mIU/L) but the lower limit was not (0.56 vs. 0.27 mIU/L). This finding may have a clinical impact since these values may lead to the misdiagnosis of euthyroid patients with subclinical hyperthyroidism.

Determination of salivary cortisol reference interval in a selected Malaysian population

@#Introduction: Salivary cortisol is used as an indicator of stress level and a recommended screening test for Cushing syndrome. The normal reference interval for salivary cortisol is dependent on the analytical methodology and the population studied and hence, establishment of a local population-based reference interval is recommended. Materials and methods: A total of 129 healthy blood donors and staffs of Penang General Hospital were recruited from June 2018-May 2019. Paired (morning and late-night) saliva samples were collected from individuals aged between 18 and 60 years old with no history of chronic medical illness. Salivary cortisol was assayed using electrochemiluminescence immunoassay technique. Non-parametric statistics were used for calculation of reference interval and 90% confidence intervals (90% CIs). Results: The reference interval for morning and latenight salivary cortisol was 2.09 – 22.63 nmol/L and <12.00 nmol/L, respectively. Conclusion: The locally-derived adult reference intervals for morning and late-night salivary cortisol concentration was determined and varied with previous studies emphasising the need in establishing individual laboratory reference interval.

Establishing reference intervals of thyroid hormone based on a laboratory information system / 中华内科杂志

Objective@#To establish reference intervals (RIs) of thyroid hormone based on data from healthy subjects in laboratory information system (LIS) by indirect methods.@*Methods@#Data were selected from the physical examination center in LIS of the First Hospital of Jilin University from May 2014 to December 2018. The normal distribution of the original data was checked by the Kolmogorov-Smirnov test. Skewed data were transformed into normal distribution using BOX-COX techniques, and outliers were identified by the Turkey method. The continuous percentile curve was established by coefficient of skewness-median-coefficient of variation(LMS) methods. Cut-off value of age was determined by decision trees, and the differences between groups were verified by Z-tests. P2.5 and P97.5 in the RIs were analyzed by non-parametric methods.@*Results@#A total of 45 742 subjects were included in the study. There were no differences in the RI for thyroid stimulating hormone (TSH) among age groups or between men and women (Z<Z*), and the RI was 0.60-4.41mIU/L (20-79 years old). However, the levels of free triiodothyronine(FT3) decreased with age in males and females under 35-year-old. The RIs for FT3 were 4.47-6.44pmol/L (20-44 years old), 4.19-6.21pmol/L (45-64 years old) and 3.90-5.85pmol/L (65-79 years old) in males, and 4.04-6.13pmol/L (20-34 years old) and 3.87-5.76pmol/L (35-79 years old) in females, respectively. The levels of free thyroxine(FT4) in men were higher than those in women from 20 to 49 years old, and no gender and age differences could be viewed in subjects after 50 years old (Z<Z*). The RIs for FT4 were 13.69-21.76pmol/L (male, 20-49 years old), 12.99-20.83pmol/L (female, 20-49 years old) and 12.98-21.21pmol/L (50~79 years old).@*Conclusion@#Establishment of RIs of thyroid hormone based on the data from LIS is simple and reliable, which is suitable for clinical laboratory application.