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Reporting a measurement procedure and its analytical performance following method evaluation in a peer-reviewed journal is an important means for clinical laboratory practitioners to share their findings. It also represents an important source of evidence base to help others make informed decisions about their practice. At present, there are significant variations in the information reported in laboratory medicine journal publications describing the analytical performance of measurement procedures. These variations also challenge authors, readers, reviewers, and editors in deciding the quality of a submitted manuscript. The International Federation of Clinical Chemistry and Laboratory Medicine Working Group on Method Evaluation Protocols (IFCC WG-MEP) developed a checklist and recommends its adoption to enable a consistent approach to reporting method evaluation and analytical performance characteristics of measurement procedures in laboratory medicine journals. It is envisioned that the LEAP checklist will improve the standardisation of journal publications describing method evaluation and analytical performance characteristics, improving the quality of the evidence base that is relied upon by practitioners. [ABSTRACT FROM AUTHOR]

In this computer simulation study, we examine four different statistical approaches of linearity assessment, including two variants of deviation from linearity (individual (IDL) and averaged (AD)), along with detection capabilities of residuals of linear regression (individual and averaged). From the results of the simulation, the following broad suggestions are provided to laboratory practitioners when performing linearity assessment. A high imprecision can challenge linearity investigations by producing a high false positive rate or low power of detection. Therefore, the imprecision of the measurement procedure should be considered when interpreting linearity assessment results. In the presence of high imprecision, the results of linearity assessment should be interpreted with caution. Different linearity assessment approaches examined in this study performed well under different analytical scenarios. For optimal outcomes, a considered and tailored study design should be implemented. With the exception of specific scenarios, both ADL and IDL methods were suboptimal for the assessment of linearity compared. When imprecision is low (3 %), averaged residual of linear regression with triplicate measurements and a non-linearity acceptance limit of 5 % produces <5 % false positive rates and a high power for detection of non-linearity of >70 % across different types and degrees of non-linearity. Detection of departures from linearity are difficult to identify in practice and enhanced methods of detection need development. [ABSTRACT FROM AUTHOR]

Interference from isomeric steroids is a potential cause of disparity between mass spectrometry-based 17-hydroxyprogesterone (17OHP) results. We aimed to assess the proficiency of mass spectrometry laboratories to report 17OHP in the presence of known isomeric steroids. A series of five samples were prepared using a previously demonstrated commutable approach. These samples included a control (spiked to 15.0 nmol/L 17OHP) and four challenge samples further enriched with equimolar concentrations of 17OHP isomers (11α-hydroxyprogesterone, 11β-hydroxyprogesterone, 16α-hydroxyprogesterone or 21-hydroxyprogesterone). These samples were distributed to 38 participating laboratories that reported serum 17OHP results using mass spectrometry in two external quality assurance programs. The result for each challenge sample was compared to the control sample submitted by each participant. Twenty-six laboratories (68 % of distribution) across three continents returned results. Twenty-five laboratories used liquid chromatography-tandem mass spectrometry (LC-MS/MS), and one used gas chromatography-tandem mass spectrometry to measure 17OHP. The all-method median of the control sample was 14.3 nmol/L, ranging from 12.4 to 17.6 nmol/L. One laboratory had results that approached the lower limit of tolerance (minus 17.7 % of the control sample), suggesting the isomeric steroid caused an irregular result. Most participating laboratories demonstrated their ability to reliably measure 17OHP in the presence of the four clinically relevant isomeric steroids. The performance of the 12 (32 %) laboratories that did not engage in this activity remains unclear. We recommend that all laboratories offering LC-MS/MS analysis of 17OHP in serum, plasma, or dried bloodspots determine that the isomeric steroids are appropriately separated. [ABSTRACT FROM AUTHOR]

Reporting a measurement procedure and its analytical performance following method evaluation in a peer-reviewed journal is an important means for clinical laboratory practitioners to share their findings. It also represents an important source of evidence base to help others make informed decisions about their practice. At present, there are significant variations in the information reported in laboratory medicine journal publications describing the analytical performance of measurement procedures. These variations also challenge authors, readers, reviewers, and editors in deciding the quality of a submitted manuscript. The International Federation of Clinical Chemistry and Laboratory Medicine Working Group on Method Evaluation Protocols (IFCC WG-MEP) developed a checklist and recommends its adoption to enable a consistent approach to reporting method evaluation and analytical performance characteristics of measurement procedures in laboratory medicine journals. It is envisioned that the Laboratory Evaluation and Analytical Performance Characteristics (LEAP) checklist will improve the standardisation of journal publications describing method evaluation and analytical performance characteristics, improving the quality of the evidence base that is relied upon by practitioners. [ABSTRACT FROM AUTHOR]

Reporting a measurement procedure and its analytical performance following method evaluation in a peer-reviewed journal is an important means for clinical laboratory practitioners to share their findings. It also represents an important source of evidence base to help others make informed decisions about their practice. At present, there are significant variations in the information reported in laboratory medicine journal publications describing the analytical performance of measurement procedures. These variations also challenge authors, readers, reviewers, and editors in deciding the quality of a submitted manuscript. The International Federation of Clinical Chemistry and Laboratory Medicine Working Group on Method Evaluation Protocols (IFCC WG-MEP) developed a checklist and recommends its adoption to enable a consistent approach to reporting method evaluation and analytical performance characteristics of measurement procedures in laboratory medicine journals. It is envisioned that the Laboratory Evaluation and Analytical Performance Characteristics (LEAP) checklist will improve the standardisation of journal publications describing method evaluation and analytical performance characteristics, improving the quality of the evidence base that is relied upon by practitioners. [ABSTRACT FROM AUTHOR]

Method evaluation is one of the critical components of the quality system that ensures the ongoing quality of a clinical laboratory. As part of implementing new methods or reviewing best practices, the peer-reviewed published literature is often searched for guidance. From the outset, Clinical Chemistry and Laboratory Medicine (CCLM) has a rich history of publishing methods relevant to clinical laboratory medicine. An insight into submissions, from editors' and reviewers' experiences, shows that authors still struggle with method evaluation, particularly the appropriate requirements for validation in clinical laboratory medicine. Here, we consider through a series of discussion points an overview of the status, challenges, and needs of method evaluation from the perspective of clinical laboratory medicine. We identify six key high-level aspects of clinical laboratory method evaluation that potentially lead to inconsistency. 1. Standardisation of terminology, 2. Selection of analytical performance specifications, 3. Experimental design of method evaluation, 4. Sample requirements of method evaluation, 5. Statistical assessment and interpretation of method evaluation data, and 6. Reporting of method evaluation data. Each of these areas requires considerable work to harmonise the practice of method evaluation in laboratory medicine, including more empirical studies to be incorporated into guidance documents that are relevant to clinical laboratories and are freely and widely available. To further close the loop, educational activities and fostering professional collaborations are essential to promote and improve the practice of method evaluation procedures. [ABSTRACT FROM AUTHOR]

Context The skeletal effects of vitamin D remain controversial and it is uncertain whether variation in serum 25-hydroxyvitamin D (25OHD) levels over time influences bone mineral density (BMD). Objective We evaluated longitudinal stability of serum 25OHD and associations with changes in BMD in participants aged 46-70 years at baseline. Methods We studied 3698 Busselton Healthy Ageing Study participants (2040 female) with serum 25OHD and dual-energy x-ray absorptiometry (DXA) BMD assessments at baseline and at ∼6 years follow-up. Restricted cubic splines were used to evaluate associations between changes in 25OHD and BMD. Results Mean season-corrected serum 25OHD was 81.3 ± 22.7 and 78.8 ± 23.1 nmol/L at baseline and 6 years, respectively, and showed moderate correlation (intraclass correlation coefficient: 0.724). Significant predictors of change in 25OHD concentration (Δ25OHD) included baseline 25OHD, change in body mass index and vitamin D supplementation at follow-up. Greater decline in serum 25OHD over time was associated with significantly greater reduction in BMD at total hip and femoral neck, but the magnitude of the differences was small (estimated differences 0.004 g/cm2 and 0.005-0.007 g/cm2, respectively, for lowest quartile of Δ25OHD compared with higher quartiles, adjusted for sex, baseline BMD, 25OHD, and demographics). No significant associations between Δ25OHD and lumbar spine BMD were observed. Increase in 25OHD levels was not associated with change in BMD. Conclusions In this predominantly vitamin D–replete middle-aged cohort, serum 25OHD showed moderate longitudinal stability. Declining serum 25OHD over time was associated with greater reduction in BMD at the total hip and femoral neck. [ABSTRACT FROM AUTHOR]

In a survey reported in 2018, up to 50% of laboratories using LC-MS/MS methods for serum 17OHP measurement did not know if their methods could separate isobaric isomers of 17OHP [[8]]. Keywords: 17-hydroxyprogesterone; congenital adrenal hyperplasia (CAH); endogenous interference EN 17-hydroxyprogesterone congenital adrenal hyperplasia (CAH) endogenous interference e64 e66 3 01/30/23 20230301 NES 230301 To the Editor, Serum 17 hydroxyprogesterone (OHP) is a key steroid for screening, diagnosis, and monitoring of congenital adrenal hyperplasia (CAH), a condition with 95% of cases due to 21 hydroxylase deficiency. If these two isomers coelute with 17OHP, they can potentially increase serum 17OHP up to 9 times the actual 17OHP concentration, resulting in falsely high 17OHP results that may affect patient management. [Extracted from the article]

Background: The presence of C3-epimer (C-3-epi-25-hydroxyvitamin D) in infant serum may complicate 25-hydroxyvitamin D (25(OH)D) measurement when using liquid chromatography tandem mass spectrometry assays that do not separately measure the epimer. We measured the concentration of C3-epi-25(OH)D in neonatal samples in Western Australian using umbilical cord blood samples and a liquid chromatography tandem mass spectrometry assay that separately quantifies 25(OH)D and C3-epi-25(OH)D.Methods: A total of 120 anonymized cord blood samples were analysed using a liquid chromatography tandem mass spectrometry assay that utilizes two CSH fluoro-phenyl columns in series. Chromatography was performed on a Waters Acquity Ultra Performance Liquid system, and quantification was using a Waters Quattro Premier XE mass spectrometer.Results: C3-epi-25(OH)D3 was detected in all umbilical cord blood samples (median 5.2 nmol/L, IQR 3.7-6.6 nmol/L) and contributed 6.6% (SD 2.6, 95% CI [6.1, 7.1]) of the total 25(OH)D concentration. Mean 25(OH)D3 measured in cord blood was 79.1 nmol/L (SD 22.7 nmol/L). A positive relationship (R(2 )= 0.35, P < 0.0005) between 25(OH)D3 levels and C3-epi-25(OH)D3 was noted in this cohort. No samples contained 25(OH)D2 or C3-epi-25(OH)D2.Conclusion: C3-epi-25(OH)D3 is present in all neonatal samples but contributes <10% of the total 25(OH)D concentration which is unlikely to be clinically significant. Liquid chromatography tandem mass spectrometry assays that do not separately quantify C3-epi-25(OH)D3 from other vitamin D metabolites may potentially overestimate neonatal 25(OH)D levels, but diagnostic misclassification in neonates is unlikely. [ABSTRACT FROM AUTHOR]

As an outcome of the 2010 Asian Pacific Conference for Chromatography and Mass Spectrometry in Hong Kong, a collaborative working group was formed to promote the harmonisation of mass spectrometry methods. The Mass Spectrometry Harmonisation Working Group resides under the combined auspices of the Asia-Pacific Federation for Clinical Biochemistry and Laboratory Medicine (APFCB) and the Australasian Association of Clinical Biochemists (AACB). A decision was made to initially focus attention on serum steroids due to the common interest of members in this area; with the first steroid to assess being testosterone. In principle, full standardisation with traceability should be achievable for all steroids as they are small compounds with defined molecular weight and structure. In order to achieve this we need certified reference materials, reference methods, reference laboratories, reference intervals and external quality assurance programs; each being an important pillar in the process. When all the pillars are present, such as for serum testosterone, it is feasible to fully standardise the liquid chromatography - tandem mass spectrometry (LC-MS/MS) methods. In a collaborative process with interested stakeholders, we commenced on a pathway to provide ongoing assessment and seek opportunities for improvement in the LC-MS/MS methods for serum steroids. Here we discuss the outcomes to date and major challenges related to the accurate measurement of serum steroids with a focus on serum testosterone. [ABSTRACT FROM AUTHOR]

Reporting a measurement procedure and its analytical performance following method evaluation in a peer-reviewed journal is an important means for clinical laboratory practitioners to share their findings. It also represents an important source of evidence base to help others make informed decisions about their practice. At present, there are significant variations in the information reported in laboratory medicine journal publications describing the analytical performance of measurement procedures. These variations also challenge authors, readers, reviewers, and editors in deciding the quality of a submitted manuscript.The International Federation of Clinical Chemistry and Laboratory Medicine Working Group on Method Evaluation Protocols (IFCC WG-MEP) developed a checklist and recommends its adoption to enable a consistent approach to reporting method evaluation and analytical performance characteristics of measurement procedures in laboratory medicine journals. It is envisioned that the LEAP checklist will improve the standardisation of journal publications describing method evaluation and analytical performance characteristics, improving the quality of the evidence base that is relied upon by practitioners.

As men age, serum testosterone (T) concentrations decrease, as do fitness, strength, and lean mass. Whether testosterone treatment confers additive benefit to reverse these changes when combined with exercise training in middle-to-older aged men remains unclear. We assessed the effects of T treatment and exercise, alone and in combination, on aerobic capacity (V̇o 2 peak), body composition, and muscular strength in men 50-70 yr, waist circumference ≥95 cm and low-normal serum T (6-14 nmol·L -1 ). Participants ( n = 80) were randomized to AndroForte5 (testosterone 5.0% wt/vol, 100 mg/2 mL) cream (T), or matching placebo (P), applied transdermally daily, and supervised center-based exercise (Ex) or no additional exercise (NEx), for 12-wk. Exercise increased V̇o 2peak and strength versus nonexercise (V̇o 2peak : T + Ex: +2.5 mL·kg -1 ·min -1 , P + Ex: +3.2 mL·kg -1 ·min -1 , P < 0.001; leg press: T + Ex: +31 kg, P + Ex: +24 kg, P = 0.006). T treatment did not affect V̇o 2peak or strength. Exercise decreased total (T + Ex: -1.7, P + Ex: -2.3 kg, P < 0.001) and visceral fat (T + Ex: -0.1 kg, P + Ex: -0.3 kg, P = 0.003), and increased total (T + Ex: +1.4 kg, P + Ex: +0.7 kg, P = 0.008) and arm lean mass (T + Ex: +0.5 kg, P + Ex: +0.3 kg, P = 0.024). T treatment did not affect total or visceral fat, but increased total (T + Ex: +1.4 kg, T + NEx: +0.7 kg, P = 0.015), leg (T + Ex: +0.3 kg, T + NEx: +0.2 kg, P = 0.024), and arm lean mass (T + Ex: +0.5 kg, T + NEx: +0.2 kg, P = 0.046). T + Ex increased arm lean mass (T + Ex: +0.5 kg vs. P + NEx: -0.0 kg, P = 0.001) and leg strength (T + Ex: +31 kg vs. P + NEx: +12 kg, P = 0.032) compared with P + NEx, with no other additive effects. Exercise training was more effective than T treatment in increasing aerobic capacity and decreasing total and visceral fat mass. T treatment at therapeutic doses increased lean mass but conferred limited additional benefit when combined with exercise. Exercise should be evaluated as an antiaging intervention in preference to testosterone treatment in men. NEW & NOTEWORTHY We illustrate that exercise training generates superior outcomes to testosterone treatment for improving aerobic fitness, muscular strength, and total and visceral fat mass in men 50-70 yr with low-normal serum testosterone concentrations. Adding testosterone treatment to exercise did not provide any additive benefit for these variables. Testosterone treatment alone and exercise alone had similar impacts on lean mass. Therefore, men unable to exercise may obtain benefit from testosterone treatment alone to improve lean mass.