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Background Serum insulin-like growth factor 1 (IGF-1) is an important biochemical tool to diagnose and monitor growth hormone (GH)-related disorders. However, ethnicity-specific Indian data, following consensus criteria for the establishment of normative data, are not available. Our objective was to generate chronological age (CA)-, bone age (BA)- and Tanner stage–specific normative data for IGF-1 in healthy Indian children and adolescents. Methods A cross-sectional epidemiological study was conducted in schools and the community, which enrolled apparently healthy children and adolescents with robust exclusion criteria. The outcome measure was serum IGF-1 assessed using an electro-chemiluminescence immunoassay (ECLIA). The 2.5th, 5th, 10th, 25th, 50th (median), 75th, 90th, 95th, and 97.5th centiles for IGF-1 were estimated using generalized additive models. Results We recruited 2226 apparently healthy participants and following exclusion, 1948 (1006 boys, 942 girls) were included in the final analysis. Girls had median IGF-1 peak at CA of 13 years (321.7 ng/mL), BA of 14 years (350.2 ng/mL) and Tanner stage IV (345 ng/mL), while boys had median IGF-1 peak at CA of 15 years (318.9 ng/mL) BA of 15 years (340.6 ng/mL) and Tanner stage III (304.8 ng/mL). Girls had earlier rise, earlier peak, and higher IGF-1 values. The reference interval (2.5th to 97.5th percentile) was broader during peripubertal ages, indicating a higher physiological variability. Conclusion This study provides ethnicity-specific normative data on serum IGF-1 and will improve the diagnostic utility of IGF-1 in the evaluation and management of growth disorders in Indian children and adolescents. [ABSTRACT FROM AUTHOR]

Background: The novel daratumumab immunotherapy is a human IgG1 kappa antibody targeted against CD38, which is almost universally expressed on myeloma plasma cells. Daratumumab has efficacy in clinical trials for the treatment of multiple myeloma; however, it complicates laboratory monitoring of the serological response to treatment, as it is detected by serum electrophoresis and/or immunofixation. Methods: Laboratory reports of electrophoresis patterns serially performed in a single laboratory of six patients with relapsed multiple myeloma receiving daratumumab therapy as part a clinical trial were reviewed retrospectively. Results: Post administration of daratumumab therapy, an additional band was visible by serum electrophoresis, migrating to the mid-gamma region, which was confirmed as IgG kappa by immunofixation. In five out of the six patients, this band was quantified at <2.0 g/L. For one patient, this band co-migrated with the patient's disease paraprotein band, so both bands were quantified together. The appearance of an apparent second paraprotein band while receiving treatment for multiple myeloma can cause anxiety for patients, confusion for healthcare workers and may also underestimate complete remission rates. Conclusions: The clinical laboratory must be aware of the interference of daratumumab in serum electrophoresis. Effective communication between clinicians and the laboratory is essential for the production of clinically valuable, non-misleading reports for these patients. [ABSTRACT FROM AUTHOR]

Objective: Sex hormone-binding globulin (SHBG) is a glycoprotein which binds hormones such as testosterone. Around 97% of circulating testosterone is bound to SHBG or albumin and is therefore biologically unavailable; 2–3% of testosterone is free. Free testosterone is very technically challenging to quantify; in order to circumvent this problem, equations using testosterone and SHBG are used to estimate free testosterone. We decided to determine the effect of using different SHBG immunoassays on calculated free testosterone results. Design: Anonymized surplus serum samples were analysed for SHBG on four different immunoassay platforms (Abbott Architect, Roche, Beckman and Siemens). The SHBG results were used to generate a Vermeulen calculated free testosterone. Results: Beckman Access and Siemens Centaur both gave results close to the overall mean. Roche gave the highest SHBG concentrations with Abbott Architect producing the lowest results. Abbott Architect gave the highest calculated free testosterone results, followed by Beckman. Roche gave the lowest results. Sixty-five per cent of male samples had low calculated free testosterone and 27.5% of the females had high calculated free testosterone using the SHBG from the Abbott assay compared with 69% low male calculated free testosterone and 20% high female calculated free testosterone with the Roche assay. Conclusion: Our results have shown significant differences in SHBG results produced by different analysers and subsequently the calculated free testosterone, which may affect result interpretation if method-specific reference ranges for calculated free testosterone are not used. Care should be taken to ensure reference ranges are appropriate for the analyser used to avoid misdiagnosis of hypo or hyperandrogenism, and ensure patients get the most appropriate treatment. [ABSTRACT FROM AUTHOR]

Background: Biomarker discovery studies often claim 'promising' findings, motivating further studies and marketing as medical tests. Unfortunately, the patient benefits promised are often inadequately explained to guide further evaluation, and few biomarkers have translated to improved patient care. We present a practical guide for setting minimum clinical performance specifications to strengthen clinical performance study design and interpretation. Methods: We developed a step-by-step approach using test evaluation and decision-analytic frameworks and present with illustrative examples. Results: We define clinical performance specifications as a set of criteria that quantify the clinical performance a new test must attain to allow better health outcomes than current practice. We classify the proposed patient benefits of a new test into three broad groups and describe how to set minimum clinical performance at the level where the potential harm of false-positive and false-negative results does not outweigh the benefits. (1) For add-on tests proposed to improve disease outcomes by improving detection, define an acceptable trade-off for false-positive versus true-positive results; (2) for triage tests proposed to reduce unnecessary tests and treatment by ruling out disease, define an acceptable risk of false-negatives as a safety threshold; (3) for replacement tests proposed to provide other benefits, or reduce costs, without compromising accuracy, use existing tests to benchmark minimum accuracy levels. Conclusions: Researchers can follow these guidelines to focus their study objectives and to define statistical hypotheses and sample size requirements. This way, clinical performance studies will allow conclusions about whether test performance is sufficient for intended use. [ABSTRACT FROM AUTHOR]