Determine Reference Intervals Research Articles

Determination of reference intervals for atomic force microscopy parameters characterizing erythrocyte size

Introduction. Atomic force microscopy (AFM) is the cutting-edge method for imaging of cells and subcellular structures, and it has wide application prospects in the laboratory diagnostics. For AFM effective using in practical medicine, it is necessary to determine the reference intervals (RI) for biological objects, particularly for erythrocytes (red blood cells). Aim.To determine the RI for AFM parameters characterizing erythrocyte size in healthy subjects. Materials and Methods. 32 blood donors aged 18–60 (22 males, 10 females) were enrolled into the study. All the participants have undergone light microscopy of a whole blood smear, clinical blood test, determination of the serum ferritin level, and AFM imaging of erythrocytes. Statistical analysis was done with SPSS, and parametrical criteria were used. RI were calculated according to the GOST (Russian State Standard) R 53022.3-2008. Results and Discussion. In all the participants, both all the parameters of clinical blood test and the ferritin serum level, were within their RI. According to light microscopy, in all the participants, erythrocytes were normocytes with unchanged form. So, investigated subjects showed their applicability to be used as the reference group for the determination of RI for AFM parameters characterizing erythrocyte size. We calculated RI and their confidential intervals for the following size parameters: minimal and maximal normocyte height, minimal and maximal normocyte diameter. Conclusion. Our results contribute to the development of AFM clinical methodology. Our results confirm the advisability of further investigations dedicated to the RI determination for AFM parameters characterizing erythrocyte size in increased samples of healthy subjects of different age groups.

Critical appraisal of two Box-Cox formulae for their utility in determining reference intervals by realistic simulation and extensive real-world data analyses

BackgroundThe reference interval (RI) is defined as the central 95 % range of reference values (RVs) from healthy individuals. The ideal method for determining RIs is to transform RV distribution into Gaussian and estimate its 95 % range parametrically. One-parameter Box-Cox formula (1pBC) is widely used for correcting skewness (Sk) or kurtosis (Kt) in data distribution. However, 1pBC is not popular for computing RIs due to its unreliability in Gaussian transformation. While its two-parameter version (2pBC) is not used due to a challenge in fitting power (λ) and shift (α) parameters simultaneously. In this study, technical issues in fitting both formulae are assessed, and an alternative algorithm for successful use of 2pBC is proposed. MethodsFor fitting 1pBC, optimal λ was determined by stepwise linear search. For 2pBC, optimal [λ, α] combination was pursued in two ways: by grid search of λ and α (2pBCgrid) or by using the grid search but keeping α-range close to the reference distribution (2pBCopt). Their accuracy and precision in determining RIs were compared by generating power-normal distributions simulating RVs of 23 major chemistry analytes. Additionally, their practical utilities were compared by analyzing 776 real-world datasets comprising test results of 25 analytes that were obtained from the global multicenter RV study of IFCC. For comparison, the performance of nonparametric method was evaluated in both settings. ResultsFor analytes with not-much-skewed distributions, unbiased estimation of RIs was accomplished by all methods. Nevertheless, when reference distributions are located far from zero, λ estimated by1pBC and 2pBCgrid fluctuated widely, which was attributable to virtually flat goodness-of-fit profile for [λ, α]. For highly skewed distributions, 1pBC caused bias in estimating RI and λ due to remotely peaked goodness-of-fit profile. Real-world data analyses revealed that 2pBCopt and 1pBC achieved Gaussian transformation (|Sk|<0.1 and |Kt|<0.3) in 82.4 % and 66.9 % among 776 datasets, respectively. Fitting bias signified by Kt<−0.4 was more common to 1pBC. The practical utility of 2pBCopt was unbiased prediction of analyte-specific distribution-shape (λ). Whereas nonparametric method gave highly variable RIs for both simulated and real-world datasets. Conclusions2pBCopt is suitable for calculating RIs and grasping distribution-shape from the estimated λ.

Reference intervals for trace mineral and heavy metal concentrations in horse livers in the Netherlands.

We determined reference intervals (RIs) for concentrations of trace minerals and toxic elements based on liver samples from 122 apparently healthy horses at 2 slaughter facilities in the Netherlands. Samples were collected during the spring and fall of 2021, and the sex and age of the horses were registered upon sampling. Concentrations of arsenic, cadmium, chromium, cobalt, copper, iron, lead, manganese, molybdenum, nickel, selenium, vanadium, and zinc were measured in liver samples using inductively coupled plasma-mass spectrometry (ICP-MS) after nitric acid digestion. RIs were calculated using Reference Value Advisor software. The concentrations of most elements were not significantly different between sexes or in different seasons. Cadmium concentrations were higher than the European maximum residue limit of 2 mg/kg DW in 89% of livers. Positive significant correlations were observed between some elements (iron, molybdenum, lead, vanadium), and significant negative correlations between others (manganese, iron).

Cardiological Reference Intervals in Adult American Staffordshire Terrier Dogs.

The aim of this study was to determine reference intervals (RI) for echocardiography, electrocardiography (ECG), vertebral heart score (VHS) measurement, and arterial systolic blood pressure (SBP) in American Staffordshire Terrier dogs. The study population included 29 clinically healthy AST dogs of different ages, genders, and body weights. SBP measurement, ECG, thoracic radiography, and echocardiography were performed on each dog. Compared to RIs available for the general population of dogs, the duration of the P wave and QRS complex was longer and VHS was higher. Moreover, the left ventricular dimension in diastole and systole, left atrial dimension, and end point to septal separation values were higher, while the interventricular septum in diastole and systole and aortic root diameter were lower compared to general similar average body weight. The AST breed has a different heart shape, which in this breed is more rounded compared to other dog breeds, especially the deep chest. The specific body structure and the shape of the heart had an impact on the results of the cardiological examination.

Determination of prolactin reference intervals in different age groups

BACKGROUND: Clinical diagnostic laboratories (CDL) have at their disposal various automated systems for the measurement of biochemical parameters and markers such as prolactin. Each of the test systems manufactures offers its own alternate design of the method, which makes standardization difficult. In endocrinological practice, the problem of result discrepancies often arises. In hormonal assays, the clinical picture of patients sometimes does not correspond to the reference values provided by the manufacturers, which determines the need to develop the method-specific reference values for a specific population. The difficulty in interpreting basal prolactin levels is not only due to a transient increase in the hormone levels caused by stress or excessive physical exertion, but also due to a significant variability of indicators in the same patient, even if all recommendations for blood sampling are followed.AIM: The aim of the study to determine the reference values in serum samples of women, men and children of different age groups for the VITROS Immunodiagnostic Systems and compare the results with the “expected prolactin levels” recommended by the method manufacturerMATERIALS AND METHODS: The monocentric study included 879 serum samples of apparently healthy subjects who were admitted to the Endocrinology Research Center. Measurements were performed using the VITROS ECi 3600 automatic chemiluminescence analyzer (Ortho-Clinical Diagnostics, Great Britain).RESULTS: For adult men and women reference values were 66–436 and 94–500 mIU/l respectively. When comparing the results of prolactin determination in women and men of the studied cohort with the “expected values” of the VITROS ECi 3600 manufacturer a systematic shift towards an increase in lower and upper limits of the reference values was found in both ­cohorts.CONCLUSION: The obtained reference values of prolactin can be use in the determination of prolactin in the Russian population for VITROS ECi 3600 Immunodiagnostic Systems.

Establishment of reference intervals for complete blood count in times of COVID-19 and vaccination.

COVID-19 and vaccination may affect some parameters of the complete blood count (CBC). The aim of this study was to determine reference intervals (RI) of CBC in healthy population with different COVID-19 and vaccination backgrounds and compare them with those established previously. A cross-sectional study was conducted in donors who attended the Traumatology Hospital "Dr. Victorio de la Fuente Narváez" (HTVFN) from June to September 2021. Reference intervals were established using the non-parametric method on Sysmex XN-1000. For differences between groups with different COVID-19 and vaccination backgrounds, non-parametric tests were used. The RI were established in 156 men and 128 women. Haemoglobin (Hb), haematocrit (Hct), red blood cells (RBC), platelets (Plt), mean platelets volume (MPV), monocytes and relative neutrophils were higher in men than women (P < 0.001). The percentiles of Hb, Hct, RBC, MPV and relative monocytes showed higher values; Plt, white blood cells (WBC), lymphocytes, monocytes, neutrophils, eosinophils and absolute basophils, the 2.5th was higher and the 97.5th was lower; for lymphocytes and relative neutrophils, both percentiles had a trend toward lower values, compared to previous RI. Differences between groups with different COVID-19 and vaccination backgrounds, in lymphocytes (P = 0.038), neutrophils (P = 0.017) and eosinophils (P = 0.018) in men; Hct (P = 0.014), RDW (P = 0.023) in women and MPV (P = 0.001) in both, were not considered pathological. The RI for the CBC were established in a Mestizo-Mexican population with different COVID-19 and vaccination backgrounds, so should be updated and validated in different hospitals close to the HTVFN that use the same analyser.

Determination of reference intervals of hemogram with advanced clinical parameters by indirect method on Sysmex XN-1000

Abstract Objectives The reference interval is the primary tool used to interpret laboratory test results. Each laboratory should determine reference intervals (RIs) that reflect their population. In this study, it was aimed to determine the RIs of hemogram routine and advanced clinical test parameters for our hospital and region by indirect method and to compare these calculated RIs with the limits recommended by the current manufacturer and the literature. Methods The hemogram results of patients aged 18–65 years who applied to Kastamonu Training and Research Hospital between July 2020 and June 2022, were included in the study. Hemogram analyzes were performed on Sysmex XN-1000 (Kobe, Japan) hematology auto analyzers. The RIs were determined by indirect method from the obtained data using the non-parametric percentage estimation method. Harris-Boyd method was used to decide on subgroup separation based on gender. Results All parameters had non-parametric distribution. RBC, HGB, HCT, MCH, MCHC, PLT, RDW-CV, RDW-SD, PCT, monocytes count, eosinophils count, monocytes % and macroR parameters which required gender-spesific RIs were determined separately for genders. Conclusions When the results are evaluated, it shows that the manufacturer’s recommendations together with the studies in the literature do not fully reflect the RIs of our population. Therefore, it is very important for each laboratory to determine its own RIs due to the differences in population, diet, technical equipment used and reference group. In addition, we think that our study will make a significant contribution to the literature, since there is insufficient data in the literature on RIs for advanced clinical parameters.

Determination of Reference Intervals of Biochemistry Parameters in healthy individuals in Gaziantep Province

A correction to this article has been published on 15 March 2024. Correction to; https://doi.org/10.58600/eurjther2088 Objective: Reference values have gained universal acceptance as the most powerful material that helps the decision-making-implementation process of the clinical laboratory. These values ​​may be affected by the geographical location, dietary habits, and other lifestyle changes of individuals applying to the clinical laboratory. Our study aims to determine the reference ranges for the biochemistry test panel, thyroid function tests, and insulin hormone levels, which are frequently needed by clinicians for the province of Gaziantep, with samples obtained from healthy individuals. Materials and Methods: In the study phase, the selection of reference individuals was carried out using the direct method a priori. For the study group, healthy individuals (224 men, 243 women) aged 18-45 were selected. Reference intervals (95% limit) were calculated according to the non-parametric method. Results: When the reference intervals obtained in our study were compared with the reference intervals of the manufacturer, there were differences (&gt; 10% lower or higher) in the upper and lower limits in urea (female and male), creatinine (male), HDL (female), AST (female and male), ALT (female), GGT (female), ALP (common), Lipase (common), CK (male), iron (male), TSH (female and male) markers. Male and female reference intervals for HDL, AST, ALT, and TSH differed significantly. Manufacturer reference ranges for these parameters were common to both sexes. Conclusion: As a result, differences were determined between most of the reference intervals obtained in our study and the reference intervals we routinely use. We think the difference in the reference intervals is due to the differences in dietary habits and environmental factors.

Evaluation and establishment of reference intervals using the i-STAT1 blood chemistry analyzer in turkeys

In veterinary medicine, point-of-care testing techniques have become popular, since they provide immediate results and only small amounts of blood are needed. The handheld i-STAT1 blood analyzer is used by poultry researchers and veterinarians; however, no studies have evaluated the accuracy of this analyzer determined reference intervals in turkey blood. The objectives of this study were to 1) investigate the effect of storage time on turkey blood analytes, 2) compare the results obtained by the i-STAT1 analyzer to those obtained by the GEM Premier 3000, a conventional laboratory analyzer, and 3) establish reference intervals for blood gases and chemistry analytes in growing turkeys using the i-Stat. For the first and second objectives, we used the CG8+ i-STAT1 cartridges to test blood from 30 healthy turkeys in triplicate and once with the conventional analyzer. To establish the reference intervals, we tested a total 330 blood samples from healthy turkeys from 6 independent flocks during a 3-yr period. Blood samples were then divided into brooder (<1 wk) and growing (1-12 wk of age). Friedman's test demonstrated significant time-dependent changes in blood gas analytes, but not for electrolytes. Bland-Altman analysis revealed that there was agreement between the i-STAT1 and the GEM Premier 300 for most of the analytes. However, Passing-Bablok regression analysis identified constant and proportional biases in the measurement of multiple analytes. Tukey's test revealed significant differences in the whole blood analytes between the means of brooding and growing birds. The data presented in the present study provide a basis for measuring and interpreting blood analytes in the brooding and growing stages of the turkey lifecycle, offering a new approach to health monitoring in growing turkeys.

Determination of high-sensitivity C-reactive protein reference intervals for apparently healthy children in Addis Ababa, Ethiopia

Objective: Since then, the reference intervals of serum hsCRP in apparently healthy Ethiopian children are unknown. Therefore, this study aimed to determine the reference intervals of serum hsCRP for apparently healthy children. Methods: In this cross-sectional study, a total of 492 apparently healthy children aged 5–17 years were recruited from residents of Addis Ababa. Well-trained professionals took anthropometric measurements. The biochemical analysis was performed with the automatic biochemical analyzer Cobas Integra 400 Plus from Roche. The 2.5th and 97.5th percentile limits were calculated using a non-parametric method as per the Clinical Laboratory Standard Institute (CLSI) guide. A box plot was used to show the distribution of hsCRP by age and gender. Furthermore, bivariate and multivariable logistic regression analyses were carried out to evaluate factors associated with elevated hsCRP levels. Percentiles were displayed by age subgroup and sex. p-values &lt;0.05 were considered statistically significant. Results: The study included 245 boys and 247 girls. For the age group of 5–11 years, the combined 2.5th and 97.5th percentiles, which can be used as a reference interval for children in Addis Ababa, were 0.15–6.78 mg/L, while for the older age group (12–17 years), the determined percentile was 0.14–4.40 mg/L. Likewise, the current study shows that never or occasionally eating vegetables and/or fruits (AOR = 2.28, 95% CI, 0.84–4.97), and being obese (AOR = 3.63, 95% CI, 1.14–11.53) were independent risk factors for elevated serum hsCRP concentrations. Conclusion: This study is the first to determine the reference intervals of hsCRP concentrations among apparently healthy Ethiopian children. Notable differences were observed in the established percentiles of hsCRP in comparison with published literature.

Neonatal reference intervals for thyroid stimulating hormone and free thyroxine assayed on a Siemens Atellica® IM analyzer: a cross sectional study

BackgroundDeriving population specific reference intervals (RIs) or at the very least verifying any RI before adoption is good laboratory practice. Siemens has provided RIs for thyroid stimulating hormone (TSH) and free thyroxine (FT4) determined on their Atellica® IM analyzer for all age groups except the neonatal age group which provides a challenge for laboratories that intend to use it to screen for congenital hypothyroidism (CH) and other thyroid disorders in neonates. We set out to determine RIs for TSH and FT4 using data obtained from neonates undergoing routine screening for CH at the Aga Khan University Hospital, Nairobi, Kenya.MethodologyTSH and FT4 data for neonates aged 30 days and below were extracted from the hospital management information system for the period March 2020 to June 2021. A single episode of testing for the same neonate was included provided both TSH and FT4 were done on the same sample. RI determination was performed using a non-parametric approach.ResultsA total of 1243 testing episodes from 1218 neonates had both TSH and FT4 results. A single set of test results from each neonate was used to derive RIs. Both TSH and FT4 declined with increase in age with a more marked decline seen in the first 7 days of life. There was a positive correlation between logFT4 and logTSH (rs (1216) = 0.189, p = < 0.001). We derived TSH RIs for the age groups 2–4 days (0.403–7.942 µIU/mL) and 5–7 days (0.418–6.319 µIU/mL), and sex specific RIs for males (0.609–7.557 µIU/mL) and females (0.420–6.189 µIU/mL) aged 8–30 days. For FT4, separate RIs were derived for the age groups 2–4 days (1.19–2.59 ng/dL), 5–7 days (1.21–2.29 ng/dL) and 8–30 days (1.02–2.01 ng/dL).ConclusionOur neonatal RIs for TSH and FT4 are different from those published or recommended by Siemens. The RIs will serve as a guide for the interpretation of thyroid function tests in neonates from sub-Saharan Africa where routine screening for congenital hypothyroidism using serum samples is done on the Siemens Atellica® IM analyzer.

Reference intervals for serum immunoglobulin A levels in Brazilian children aged 1 to 10 years: a population-based study

ObjectiveTo determine reference intervals (RI) for serum immunoglobulin A (IgA) levels in healthy children aged 1 to 1 0 years residing in the central region of Brazil. MethodsThis cross-sectional study was conducted on 1,743 healthy children randomly selected from kindergartens and public schools in Cuiabá, MT, Brazil. The IgA RIs were defined using the statistical methods postulated by the guidelines of the United States Clinical and Laboratory Standards Institute, the nonparametric bootstrap method, and Horn's robust method after the correction of discrepancies by Tukey's, Dixon's, and Horn's methods, respectively. The results were defined based on the values contained between the 2.5th and 97.5th percentiles and their respective 95% confidence intervals. ResultsPartition by sex was not necessary to determine the IgA RI of the studied children. Homogeneous subgroups were identified among children aged 1–<2, 2–<5, and 5–<11 years, whose IgA-specific RIs were determined. ConclusionThe serum IgA RIs were established for three groups of Brazilian children aged 1–11 years, which differed from those currently applied in Brazilian pediatric practice and from those defined by international studies. This definition will help Brazilian pediatricians formulate an accurate diagnosis and facilitate decision-making.

Improved diagnostics of purine and pyrimidine metabolism disorders using LC-MS/MS and its clinical application.

To develop a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to quantify 41 different purine and pyrimidine (PuPy) metabolites in human urine to allow detection of most known disorders in this metabolic pathway and to determine reference intervals. Urine samples were diluted with an aqueous buffer to minimize ion suppression. For detection and quantification, liquid chromatography was combined with electrospray ionization, tandem mass spectrometry and multiple reaction monitoring. Transitions and instrument settings were established to quantify 41 analytes and nine stable-isotope-labeled internal standards (IS). The established method is precise (intra-day CV: 1.4-6.3%; inter-day CV: 1.3-15.2%), accurate (95.2% external quality control results within ±2 SD and 99.0% within ±3 SD; analyte recoveries: 61-121%), sensitive and has a broad dynamic range to quantify normal and pathological metabolite concentrations within one run. All analytes except aminoimidazole ribonucleoside (AIr) are stable before, during and after sample preparation. Moreover, analytes are not affected by five cycles of freeze-thawing (variation:-5.6 to 7.4%), are stable in thymol (variation:-8.4 to 12.9%) and the lithogenic metabolites also in HCl conserved urine. Age-dependent reference intervals from 3,368 urine samples were determined and used to diagnose 11 new patients within 7 years (total performed tests: 4,206). The presented method and reference intervals enable the quantification of 41 metabolites and the potential diagnosis of up to 25 disorders of PuPy metabolism.

Serum biochemical reference interval determination inwild Siberian weasel (Mustela sibirica).

Determining reference intervals (RI) isavaluable asset for assessing the health ofwildlife species. This isthe first study toestablish serum biochemical RIs inSiberian weasels. Forty-two healthy free-ranging Siberian weasels were captured live and brought toSeoul Wildlife Center between June 2021 and August 2022. Blood samples from 42healthy Siberian weasels ofboth sexes were used tocalculate RIs. Anautomated analyser was used toperform serum biochemistry profiles. The American Society for Veterinary Clinical Pathology recommendations were used tocalculate anonparametric RI with 90% confidence intervals. The RIs ofalbumin, total protein, globulin, calcium, glucose, blood urea nitrogen, phosphorus, amylase, cholesterol, alanine aminotransferase, total bilirubin, alkaline phosphatase, creatinine, and creatine kinase were determined. The RIs established inthis study will serve asagood starting point for analysing serum biochemical data inSiberian weasels.

Comparison of agarose gel and capillary zone electrophoresis methods with preliminary reference interval generation using capillary zone electrophoresis in bald eagles (Haliaeetus leucocephalus).

Electrophoresis can be used to aid in the diagnosis of different diseases in avian species. Capillary zone electrophoresis (CZE) is an automated method that is proposed to be superior to the dye methods used in agarose gel electrophoresis (AGE). However, reference intervals (RIs) for CZE in avian species and comparison studies between electrophoretic methods are lacking. The goals of the current study were to compare AGE and CZE methods and determine reference intervals for CZE using plasma from bald eagles (Haliaeetus leucocephalus). Heparinized plasma samples from 44 bald eagles (mean age 18.7 years) under managed care were examined by AGE and CZE. Method comparison analyses were completed, as well as the generation of preliminary RIs using the CZE method and ASVCP guidelines. Passing-Bablok regression and Bland-Altman plots demonstrate that these methods are not equivalent. All fractions were significantly correlated between the methods except for alpha 1 globulin. Inter-assay and intra-assay CVs for CZE were lower or comparable to AGE and ranged from 2.4% to 15.4%, and 0.8% to 8.3%, respectively. CZE resolved more fractions than AGE with two fractions observed in the beta and gamma region vs one for AGE in each region. CZE provided improved resolution and reproducibility for the quantitation of protein fractions in the bald eagle. Although most fraction results correlated with AGE, these methods were judged as not equivalent, necessitating method-specific Rls. Reference intervals generated from a limited number of mostly aged individuals under managed care should be considered preliminary; additional studies will aid in the production of more robust intervals.

Indirectly determined reference intervals for automated white blood cell differentials of pediatric patients in Berlin and Brandenburg.

Establishing direct reference intervals for pediatric patients is a costly, challenging, and time-consuming enterprise. Indirectly established reference intervals can help to ameliorate this situation. It was our objective to establish population-specific reference intervals for automated white blood cell differentials via data mining and non-parametric percentile method. Blood counts and automated white blood cell differentials of patients aged 0days to 18years, performed from the 1st of January 2018 until the 30th of June 2022, wereidentified in our laboratory information system. Reference intervals were established in accordance with IFCC and CLSI recommendations as well as the propositions by Haeckel etal. Initially, 47,173 blood counts on our SYSMEX XN-9000 were identified. 11,707 data sets were excluded, leaving 35,466 sample sets for analysis. Of these, 17,616 contained automated white blood cell differentials. Due to insufficient patient numbers, no reference intervals for automated white blood cell differentials could be established for children aged <7months. In comparison to the corresponding reference intervals published by Herklotz etal., reference intervals determined by us showed relevant differences throughout all age groups. The combination of non-parametric percentile method and the propositions by Haeckel etal. utilizing conscientious data mining appears to be potent alternative to direct reference interval determination.

Substantiating reference values of active anterior rhinomanometry in children aged 4-14

Objective diagnostics of nasal breathing disorders in children is a vital issue given frequent inconsistency between patients' subjective feelings and actual nasal patency. Active anterior rhinomanometry (AAR) is an objective procedure and the golden standard for nasal breathing evaluation. But still, there are no actual data in literature on relevant criteria used to evaluate nasal breathing in children. To determine reference values for indicators evaluated by active anterior rhinomanometry in Caucasian children aged 4-14 based on statistical data. Overall, we examined 659 healthy children of both sexes who were divided into 7 groups as per their height. All children included into our research underwent AAR according to the conventional procedure. AAR indicators (Summary Flow left, Summary Flow right, Summary Flow, Summary Resistance left, Summary Resistance right and Summary Resistance Flow) are given as median (Me) and values of 2.5, 25, 75, and 97.5 percentiles. We determined direct moderate, significant and strong correlations between summary speed of the flow and resistance in both nasal passages and separate speeds of the flow and right and left resistance in inhalation and exhalation (r=0.46-0.98, p<0.001). We also established weak correlations between AAR indicators and age (r= -0.08-0.11), and between ARR indicators and height (r= -0.07-0.15). Reference values for AAR indicators were successfully determined. AAR indicators are likely to be determined bearing a child's height in mind. Determined reference intervals can be applied in clinical practice.

Determination of Complete Blood Count Reference Intervals by an Indirect Method for Newborns, Adults, and Geriatric Ages.

The availability of a reliable reference interval is crucial for clinical decision-making. Correctly defined reference intervals for different age groups are currently unavailable for many parameters. Our study aimed to determine the complete blood count reference intervals in our region from newborn to geriatric ages with an indirect method. The study was carried out at Marmara University Pendik E&R Hospital Biochemistry Laboratory between January 2018 and May 2019 using the laboratory information system data. The complete blood count (CBC) measurements were performed by Unicel DxH 800 Coulter Cellular Analysis System (Beckman Coulter, FL, USA). A total of 14,014,912 test results belonging to infants, children, adolescents, adults, and geriatric ages were collected. We analyzed 22 CBC parameters, and an indirect method was used for reference interval determination. Data were analyzed according to the Clinical and Laboratory Standards Institute (CLSI) C28-A3 guideline for defining, establishing, and verifying reference intervals in the clinical laboratory. We have established reference intervals from newborn to geriatric ages for 22 hematology parameters [hemoglobin (Hb), hematocrit (Hct), red blood cell (RBC), mean red cell volume (MCV), mean red cell hemoglobin (MCH), mean red cell hemoglobin concentration (MCHC), red cell distribution width (RDW), white blood cell (WBC) count, WBC differentials, including percentages and absolute counts, platelet count, platelet distribution width (PDW), mean platelet volume (MPV) and plateletcrit (PCT)]. Our study showed that reference intervals established with data obtained from clinical laboratory databases are comparable to those created using direct methods.

Electromyography of the External Anal Sphincter during Micturition and Electrophysiological Bulbocavernosus Reflex in Healthy Spayed Female Canines.

This study aimed to find methods and interferences and illustrate the pattern of external anal sphincter (EAS) electromyography (EMG) during micturition and to determine reference intervals of electrophysiological bulbocavernosus reflex (EBCR) by using robust statistical methods in healthy spayed female canines. Ten healthy spayed female canines (no breed restriction) with a body weight of 11.3-18 kg were enrolled. EAS EMG during micturition and the EBCR test were performed under light general anesthesia. Altogether 25 out of 34 EAS EMG showed a similar pattern, including low-amplitude high-frequency bursting pattern before voiding, medium- or high-amplitude low-frequency bursting pattern at the beginning of voiding, oscillate medium- and/or high-amplitude low-frequency bursting with a low-amplitude high-frequency bursting pattern during voiding, and high-amplitude high-frequency bursting pattern at the end of voiding. An average of 100 consecutive stimulations of EBCR for one cycle were performed in each dog and another cycle was repeated to ensure reproducibility. The lower and upper limits of the reference interval of EBCR onset latency values and EBCR mean amplitude values were calculated using both standard and robust methods with untransformed and transformed Box-Cox data. The EBCR onset latency was between 13.85 and 27.44 milliseconds, whereas the EBCR mean baseline to peak amplitude was not transformed with Box-Cox transformation. All EBCR compound muscle action potentials started with a negative sharp wave, which tapers from the baseline in the upward direction, showing an upturned bell-shaped curve. In conclusion, this study was possibly the first to examine the method and provide the electrographic pattern of EAS EMG during micturition and reference intervals of EBCR onset latency in spayed female dogs, which may serve as baseline information to help veterinarians differentiate healthy from diseased dogs. Further studies should compare normal dogs and dogs with lower urinary tract abnormalities at different lesion locations.

Verification of sex- and age-specific reference intervals for 13 serum steroids determined by mass spectrometry: evaluation of an indirect statistical approach.

Conventionally, reference intervals are established by direct methods, which require a well-characterized, obviously healthy study population. This elaborate approach is time consuming, costly and has rarely been applied to steroid hormones measured by mass spectrometry. In this feasibility study, we investigate whether indirect methods based on routine laboratory results can be used to verify reference intervals from external sources. A total of 11,259 serum samples were used to quantify 13 steroid hormones by mass spectrometry. For indirect estimation of reference intervals, we applied a "modified Hoffmann approach", and verified the results with a more sophisticated statistical method (refineR). We compared our results with those of four recent studies using direct approaches. We evaluated a total of 81 sex- and age-specific reference intervals, for which at least 120 measurements were available. The overall agreement between indirectly and directly determined reference intervals was surprisingly good as nearly every fourth reference limit could be confirmed by narrow tolerance limits. Furthermore, lower reference limits could be provided for some low concentrated hormones by the indirect method. In cases of substantial deviations, our results matched the underlying data better than reference intervals from external studies. Our study shows for the first time that indirect methods are a valuable tool to verify existing reference intervals for steroid hormones. A simple "modified Hoffmann approach" based on the general assumption of a normal or lognormal distribution model is sufficient for screening purposes, while the refineR algorithm may be used for a more detailed analysis.