Determining biological variation of serum parathyroid hormone in healthy
adults

Introduction: Measurement of parathyroid hormone (PTH) is essential in the investigation and management of calcium metabolism disorders. To assess the significance of any assay result when clinical decision making biological variation (BV) of the measurand must be taken into consideration. The aim of the present study is determining the BV parameters for serum PTH. Materials and methods: Blood samples were taken at weekly intervals from 20 healthy subjects for ten weeks in this prospective BV study. Serum “intact PTH” concentrations were measured with electrochemiluminescence method. Biological variation parameters were estimated using the approach proposed by Fraser. Results: The values of within-subject biological variation (CVI), between-subject biological variation (CVG), analytical variation (CVA), reference change value (RCV) and individuality index (II) for serum PTH were 21.1%, 24.9%, 3.8%, 59.4% and 0.8%, respectively. Within-subject biological variation and CVG were also determined according to gender separately; 18.5% and 24.0%; 26.2% and 18.6% for male and female, respectively. Calculated desirable precision and bias goals were < 10.6% and < 6.3%, respectively. Conclusion: This study may contribute to BV data on serum PTH as it includes a sufficient number of volunteers from both genders over an acceptable period of time. We do not recommend the usage of population-based reference intervals for serum PTH concentrations. Reference change value may be helpful for the evaluation of serial serum PTH results. Nonetheless, evaluation of data according to gender is necessary when setting analytical performance specifications.

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Annual biological variation and personalized reference intervals of clinical chemistry and hematology analytes

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2021-0479 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Shuo Wang ◽

Min Zhao ◽

Zihan Su ◽

Runqing Mu

Keyword(s):

Clinical Chemistry ◽

Population Based ◽

Reference Intervals ◽

Biological Variation ◽

Annual Data ◽

Healthy Individuals ◽

Reference Change Value ◽

Index Of Individuality ◽

Personalized Diagnosis

Abstract Objectives A large number of people undergo annual health checkup but accurate laboratory criterion for evaluating their health status is limited. The present study determined annual biological variation (BV) and derived parameters of common laboratory analytes in order to accurately evaluate the test results of the annual healthcare population. Methods A total of 43 healthy individuals who had regular healthcare once a year for six consecutive years, were enrolled using physical, electrocardiogram, ultrasonography and laboratory. The annual BV data and derived parameters, such as reference change value (RCV) and index of individuality (II) were calculated and compared with weekly data. We used annual BV and homeostatic set point to calculate personalized reference intervals (RIper) which were compared with population-based reference intervals (RIpop). Results We have established the annual within-subject BV (CVI), RCV, II, RIper of 24 commonly used clinical chemistry and hematology analytes for healthy individuals. Among the 18 comparable measurands, CVI estimates of annual data for 11 measurands were significantly higher than the weekly data. Approximately 50% measurands of II were <0.6, the utility of their RIpop were limited. The distribution range of RIper for most measurands only copied small part of RIpop with reference range index for 8 measurands <0.5. Conclusions Compared with weekly BV, for annual healthcare individuals, annual BV and related parameters can provide more accurate evaluation of laboratory results. RIper based on long-term BV data is very valuable for “personalized” diagnosis on annual health assessments.

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Total Amylase and Pancreatic Isoamylase in Serum and Urine: Considerations from Data on Biological Variation

Annals of Clinical Biochemistry International Journal of Laboratory Medicine ◽

10.1177/000456328902600407 ◽

1989 ◽

Vol 26 (4) ◽

pp. 335-340 ◽

Cited By ~ 6

Author(s):

Steven T Cummings ◽

Callum G Fraser

Keyword(s):

Clinical Decision Making ◽

Amylase Activity ◽

Clinical Decision ◽

Population Based ◽

Reference Intervals ◽

Similar Data ◽

Creatinine Ratio ◽

Additional Information ◽

Pancreatic Isoamylase ◽

Urine Amylase

The analytical, within-subject and between-subject components of variation were estimated for amylase activity and pancreatic isoamylase activity in serum measured using newer analytical methods. Desirable analytical imprecisions based on within-subject variation were CV ≤ 4·4% and CV ≤ 7·0%, respectively. Conventional population-based reference intervals were not useful because of marked individuality; clinical decision-making points should be derived from the desired sensitivity and specificity. Serial results must change more than about 30% and 40% respectively before significance (P ≤ 0·05) can be claimed. Similar data on total amylase and pancreatic isoamylase activities in random and first morning urines showed that the use of conventional reference intervals was appropriate. Very large changes (> 100%) were required before a difference in serial results was significant. Calculation of the urine amylase/creatinine ratio appeared to confer no advantage. Derivation of the ratio of pancreatic isoamylase to total amylase activity in serum or urine was unlikely to provide additional information of value in either diagnosis or monitoring.

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BioVar: an online biological variation analysis tool

Turkish Journal of Biochemistry ◽

10.1515/tjb-2019-0437 ◽

2020 ◽

Vol 45 (5) ◽

pp. 479-489

Author(s):

Selçuk Korkmaz ◽

Gökmen Zarasız ◽

Dinçer Göksülük ◽

Mehmet Senes ◽

Cem Sönmez ◽

...

Keyword(s):

Statistical Analysis ◽

Laboratory Tests ◽

Clinical Decision Making ◽

Clinical Decision ◽

Reference Intervals ◽

Biological Variation ◽

Analysis Tool ◽

Steady State Condition ◽

Practical Applications ◽

Link Type

AbstractObjectivesBiological variation (BV) analysis of laboratory tests gets increased attention due to its practical applications. These applications include correct interpretation of laboratory tests, the decision on the availability of reference intervals, contributions to clinical decision-making. It is critical to derive the BV information accurately and reliably. Another crucial step is to perform the statistical analysis of the BV data. Although there are updated and comprehensive guidelines, there is no reliable and comprehensive tool to perform statistical analysis of BV data.MethodsWe presented BioVar, an online tool for statistical analysis of the BV data based on available and updated guidelines.ResultsThis tool can be used (i) to detect outliers, (ii) to control normality assumption, (iii) to check steady-state condition, (iv) to test homogeneity assumptions, (v) to perform subset analysis for genders, (vi) to perform analysis of variance to estimate components of variation and (vii) to identify analytical performance specifications of laboratory tests. Moreover, plots can be created at each step of outlier detection to inspect outliers and compare gender groups visually. An automatic report can be generated and downloaded.ConclusionThe tool is freely available through turcosa.shinyapps.io/biovar/, and source code is available on the Github: github.com/selcukorkmaz/BioVar.

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

Turkish Journal of Biochemistry ◽

10.1515/tjb-2020-0298 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Ceylan Bal ◽

Serpil Erdogan ◽

Gamze Gök ◽

Cemil Nural ◽

Betül Özbek ◽

...

Keyword(s):

Adult Population ◽

Reference Intervals ◽

Serum Copper ◽

Biological Variation ◽

Serum Samples ◽

Reference Change Value ◽

Index Of Individuality ◽

Copper Zinc ◽

Clinically Significant ◽

Analytical Variation

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

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Frailty Changes Predict Mortality in 4 Longitudinal Studies of Aging

The Journals of Gerontology Series A ◽

10.1093/gerona/glaa266 ◽

2020 ◽

Author(s):

Erwin Stolz ◽

Emiel O Hoogendijk ◽

Hannes Mayerl ◽

Wolfgang Freidl

Keyword(s):

Mortality Risk ◽

Clinical Decision Making ◽

Frailty Index ◽

Credible Interval ◽

Clinical Decision ◽

Population Based ◽

Time To Event Data ◽

Longitudinal Aging Study Amsterdam ◽

Aging Study ◽

Longitudinal Aging Study

Abstract Background Baseline frailty index (FI) values have been shown to predict mortality among older adults, but little is known about the effects of changes in FI on mortality. Methods In a coordinated approach, we analyzed data from 4 population-based cohorts: the Health and Retirement Study (HRS), the Survey of Health, Ageing and Retirement in Europe (SHARE), the English Longitudinal Survey of Ageing (ELSA), and the Longitudinal Aging Study Amsterdam (LASA), comprising a total of 24 961 respondents (65+), 95 897 observations, up to 9 repeated FI assessments, and up to 23 years of mortality follow-up. The effect of time-varying FI on mortality was modeled with joint regression models for longitudinal and time-to-event data. Results Differences (of 0.01) in current FI levels (hazard ratio [HR] = 1.04, 95% credible interval [CI] = 1.03–1.05) and baseline FI levels (HR = 1.03, 95% CI = 1.03–1.05) were consistently associated with mortality across studies. Importantly, individuals with steeper FI growth also had a higher mortality risk: An increase in annual FI growth by 0.01 was associated with an increased mortality risk of HR = 1.56 (95% CI = 1.49–1.63) in HRS, HR = 1.24 (95% CI = 1.13–1.35) in SHARE, HR = 1.40 (95% CI = 1.25–1.52) in ELSA, and HR = 1.71 (95% CI = 1.46–2.01) in LASA. Conclusions FI changes predicted mortality independently of baseline FI differences. Repeated assessment of frailty and individual’s frailty trajectory could provide a means to anticipate further health deterioration and mortality and could thus support clinical decision making.

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Pediatric reference interval verification for endocrine and fertility hormone assays on the Abbott Alinity system

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2021-0337 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Mary Kathryn Bohn ◽

Siobhan Wilson ◽

Alexandra Hall ◽

Khosrow Adeli

Keyword(s):

Clinical Decision Making ◽

De Novo ◽

Reference Interval ◽

Clinical Decision ◽

Reference Intervals ◽

Healthy Children ◽

Confidence Limits ◽

Test Results ◽

Serum Samples ◽

Abbott Architect

Abstract Objectives The Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) has developed an extensive database of reference intervals (RIs) for several biomarkers on various analytical systems. In this study, pediatric RIs were verified for key immunoassays on the Abbott Alinity system based on the analysis of healthy children samples and comparison to comprehensive RIs previously established for Abbott ARCHITECT assays. Methods Analytical performance of Alinity immunoassays was first assessed. Subsequently, 100 serum samples from healthy children recruited with informed consent were analyzed for 16 Alinity immunoassays. The percentage of test results falling within published CALIPER ARCHITECT reference and confidence limits was determined. If ≥ 90% of test results fell within the confidence limits, they were considered verified based on CLSI guidelines. If <90% of test results fell within the confidence limits, additional samples were analyzed and new Alinity RIs were established. Results Of the 16 immunoassays assessed, 13 met the criteria for verification with test results from ≥ 90% of healthy serum samples falling within the published ARCHITECT confidence limits. New CALIPER RIs were established for free thyroxine and prolactin on the Alinity system. Estradiol required special considerations in early life. Conclusions Our data demonstrate excellent concordance between ARCHITECT and Alinity immunoassays, as well as the robustness of previously established CALIPER RIs for most immunoassays, eliminating the need for de novo RI studies for most parameters. Availability of pediatric RIs for immunoassays on the Alinity system will assist clinical laboratories using this new platform and contribute to improved clinical decision-making.

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Music Therapy Pre-internship Education and Training: Support for a Methods-Based Approach

Music Therapy Perspectives ◽

10.1093/mtp/miab026 ◽

2021 ◽

Author(s):

Susan C Gardstrom ◽

James Hiller ◽

Annie Heiderscheit ◽

Nancy L Jackson

Keyword(s):

Music Therapy ◽

Best Practice ◽

Clinical Decision Making ◽

Well Being ◽

Clinical Decision ◽

Education And Training ◽

Population Based ◽

Music Therapists ◽

Training Support ◽

And Training

Abstract As music therapists, music is our primary realm of understanding and action and our distinctive way of joining with a client to help them attain optimal health and well-being. As such, we have adopted and advocate for a music-focused, methods-based (M-B) approach to music therapy pre-internship education and training. In an M-B approach, students’ learning is centered on the 4 music therapy methods of composing, improvising, re-creating, and listening to music and how these music experiences can be designed and implemented to address the health needs of the diverse clientele whom they will eventually encounter as practicing clinicians. Learning is highly experiential, with students authentically participating in each of the methods and reflecting on these self-experiences as a basis for their own clinical decision-making. This is differentiated from a population based (P-B) approach, wherein students’ attention is directed at acquiring knowledge about the non-musical problems of specific “clinical populations” and the “best practice” music interventions that are presumed to address these problems. Herein, we discuss both approaches, identifying the limitations of a P-B perspective and outlining the benefits of an M-B curriculum and its relevance to 21st-century music therapy practice.

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Abstract P036: Parathyroid Hormone is Associated with All-Cause and Cardiovascular Mortality: The Hoorn Study

Circulation ◽

10.1161/circ.127.suppl_12.ap036 ◽

2013 ◽

Vol 127 (suppl_12) ◽

Author(s):

Adriana J van Ballegooijen ◽

Ilse Reinders ◽

Marjolein Visser ◽

Jacqueline M Dekker ◽

Giel Nijpels ◽

...

Keyword(s):

Parathyroid Hormone ◽

Cox Regression ◽

Threshold Model ◽

Older Men ◽

Population Based ◽

Survival Curves ◽

Men And Women ◽

Serum Pth ◽

Older Men And Women ◽

Cvd Mortality

Introduction Higher parathyroid hormone (PTH) concentrations have been associated with increased cardiovascular disease (CVD) mortality, although data in the general population are scarce. Hypothesis We hypothesize that higher serum PTH concentrations are associated with all-cause and CVD mortality in a prospective, population-based cohort of older men and women. Methods We included 633 participants of the Hoorn Study, a population-based cohort with oversampling of subjects with impaired glucose regulation; mean age 70.1±6.6 years, 50.7% female. Serum intact PTH concentrations were measured using a 2-site immunoassay. Outcomes were all-cause and CVD mortality based on clinical files and coded according to the ICD-9. We used Cox-regression to estimate survival curves and hazard ratios (HR 95% CI) for all-cause and CVD mortality adjusted for potential confounders using season-specific PTH quartiles. Results During a median follow-up of 7.8 years, 112 participants died, of which 26 deaths (23%) were due to CVD. Survival curves showed an impaired survival for all-cause (Log-rank p=0.054) and CVD mortality (Log-rank p=0.022) for people in the highest PTH quartile (Figure 1). In a multivariate model adjusted for age, sex, smoking, education level, BMI, glucose status, systolic blood pressure, anti-hypertensive drug use, the highest PTH quartile was associated with higher all-cause mortality; HR 1.98 (1.08, 3.64). Kidney function (estimated glomerular filtration rate and micro-albuminuria) attenuated the PTH risk association, but risk persisted; HR 1.93 (95% CI 1.04, 3.58). The results for CVD mortality showed a similar pattern, although the association was only significant in a threshold model (Quartile 4 vs. Quartile 1-3) HR 2.56 (1.11, 5.94). Conclusion In conclusion, among older men and women, higher PTH concentrations are associated with higher mortality risk. We suggest to evaluate whether individuals with high PTH concentrations benefit from therapeutic approaches targeted to decrease PTH concentrations.

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Biological Variation: The Effect of Different Distributions on Estimated Within-Person Variation and Reference Change Values

Clinical Chemistry ◽

10.1373/clinchem.2015.252296 ◽

2016 ◽

Vol 62 (5) ◽

pp. 725-736 ◽

Cited By ~ 38

Author(s):

Thomas Røraas ◽

Bård Støve ◽

Per Hyltoft Petersen ◽

Sverre Sandberg

Keyword(s):

Computer Simulations ◽

Standard Method ◽

Simulated Data ◽

Biological Variation ◽

Nonparametric Method ◽

Anova Model ◽

Reference Change Value ◽

Performance Specifications ◽

The Impact ◽

True Values

Abstract BACKGROUND Good estimates of within-person biological variation, CVI, are essential for diagnosing and monitoring patients and for setting analytical performance specifications. The aim of the present study was to use computer simulations to evaluate the impact of various measurement distributions on different methods for estimating CVI and reference change value (RCV). METHOD Data were simulated on the basis of 3 models for distributions of the within-person effect. We evaluated 3 different methods for estimating CVI: standard ANOVA, ln-ANOVA, and CV-ANOVA, and 3 different methods for calculating RCV: classic, ln-RCV, and a nonparametric method. We estimated CVI and RCV with the different methods and compared the results with the true values. RESULTS The performance of the methods varied, depending on both the size of the CVI and the type of distributions. The CV-ANOVA model performed well for the estimation of CVI with all simulated data. The ln-RCV method performed best if data were ln-normal distributed or CVI was less than approximately 12%. The nonparametric RCV method performed well for all simulated data but was less precise. CONCLUSIONS The CV-ANOVA model is recommended for both calculation of CVI and the step-by-step approach of checking for outliers and homogeneity in replicates and samples. The standard method for calculation of RCV should not be used when using CVs.

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Reference intervals and biological variation for kallikrein 6: influence of age and renal failure

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2012-0075 ◽

2012 ◽

Vol 50 (5) ◽

Author(s):

Eduardo Martínez-Morillo ◽

Anastasia Diamandis ◽

Eleftherios P. Diamandis

Keyword(s):

Renal Failure ◽

Significant Positive Correlation ◽

Reference Interval ◽

Serum Marker ◽

Reference Intervals ◽

Biological Variation ◽

Serum Samples ◽

Positive Correlation ◽

Reference Change Value ◽

Kallikrein 6

AbstractKallikrein 6 (KLK6) is a serine protease involved in numerous cellular processes, up-regulated in many cancers and associated with some neurodegenerative disorders. The aim of this study was to establish a reference interval and estimate the biological variation of KLK6 in serum samples of adults. Furthermore, levels of this protein in patients with renal failure were also studied.Serum samples from healthy volunteers (n=136) were collected. Between 15 and 18 additional samples from four of these subjects were obtained over a period of 2 months. Samples from individuals (n=1043) who visited the University Health Network for a routine check-up were collected to study the association between KLK6 with age and gender. Samples from patients with renal failure (n=106) were also obtained and KLK6 and creatinine concentrations were analyzed by ELISA and an automated enzymatic method, respectively.The reference interval was established to be 1.04–3.93 ng/mL. The index of individuality was 0.43 and the reference change value was 35%. Only two serum samples would be required to estimate the homeostatic setting point of an individual. There is a weak but highly significant positive correlation between KLK6 and age (p<0.0001). Furthermore, there is a significant positive correlation between serum concentrations of KLK6 and creatinine (p<0.0001), in patients with renal failure.The established reference interval for KLK6 and the estimation of its biological variation will further aid in the clinical use of this protein as a serum marker of malignancy and other diseases.

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