The Adrenal Vein Sampling Outcomes Study (AVOS): success rates following adrenalectomy for unilateral primary aldosteronism.

The objective was to determine the clinical and biochemical success rates and assess the nature of follow-up after adrenalectomy in patients with unilateral primary aldosteronism (PA), subtyped by adrenal vein sampling (AVS) in West Australia (WA) using the Primary Aldosteronism Surgical Outcome (PASO) criteria. Clinical and biochemical outcomes were retrospectively evaluated in patients with unilateral PA who underwent adrenalectomy according to AVS between September 2017 and September 2020. Pre- and post-surgical data were collected using a standardised questionnaire, review of clinic letters and examination of private and public pathology results and radiological reports. Follow-up data were available for 47 patients post-adrenalectomy; biochemical outcome data were available for 37 patients, clinical outcome data for 40 patients, with 30 patients having both outcomes available. Final assessment was performed between 0 to 3 months in 23/37 (62.2%) patients with biochemical outcomes, 15/40 (37.5%) with clinical outcomes, and 17/30 (56.7%) with both clinical and biochemical outcomes. Complete biochemical success was achieved in 83.8% (31/37) of patients, with 26.7% (8/30) obtaining both complete clinical and biochemical success. Complete clinical success was achieved in 35.0% (14/40) of patients, with 47.5% (19/40) obtaining partial clinical success. Overall, 93.6% (44/47) of patients derived benefit from adrenalectomy. The outcomes of adrenalectomy for unilateral PA in Western Australian using standardised PASO criteria demonstrate highly comparable clinical and biochemical success rates to international data. However, further standardisation of post-operative follow-up care needs to be implemented to ensure the recommended repeat follow-up assessment criteria are collected.

Practical Considerations for the Clinical Application of Bone Turnover Markers in Osteoporosis.

Bone turnover markers (BTMs) are released during the bone remodelling cycle and are measurable in blood or urine, reflecting bone remodelling rate. They have been useful in elucidating the pharmacodynamics and effectiveness of osteoporosis medication in clinical trials and are increasingly used in routine clinical management of osteoporosis, especially for monitoring therapy, in addition to their use in other metabolic bone disease such as Paget's disease of bone and osteomalacia. Serum ß isomerised C-terminal telopeptide of type I collagen and pro-collagen I N-terminal propeptide have been designated as reference BTMs for use in osteoporosis. In addition, bone-specific isoenzyme of alkaline phosphatase (B-ALP) secreted by osteoblasts and tartrate-resistant acid phosphatase 5b (TRACP-5b) secreted by osteoclasts are also found to be specific markers of bone formation and resorption, respectively. The concentrations of the latter enzymes in blood measured by immunoassay provide reliable measures of bone turnover even in the presence of renal failure. B-ALP is recommended for use in the assessment of renal bone disease of chronic kidney disease, and TRACP-5b shows promise as a marker of bone resorption in that condition. BTMs in blood do not suffer from biological variation to the same extent as the older BTMs that were measured in urine. Appropriate patient preparation and sample handling are important in obtaining accurate measures of BTMs for clinical use. Reference change values and treatment targets have been determined for the reference BTMs for their use in monitoring osteoporosis treatment. Further ongoing studies will enhance their clinical applications.

Current use of bone turnover markers in the management of osteoporosis.

The adult bone is continuously being remodelled to repair microdamage, preserve bone strength and mechanical competence as well as maintain calcium homeostasis. Bone turnover markers are products of osteoblasts (bone formation markers) and osteoclasts (bone resorption markers) providing a dynamic assessment of remodelling (turnover). Resorption-specific bone turnover markers are typically degradation products of bone collagen molecules (N- [NTX] and C-telopeptide cross-linked type 1 collagen [CTX]), which are released into the circulation and excreted in urine; or enzymatic activities reflecting osteoclastic resorption, tartrate-resistant acid phosphatase [TRACP]. Formation-specific bone turnover markers embrace different osteoblastic activities: type 1 collagen synthesis (Procollagen type I N- propeptide [PINP]), osteoblast enzymes (bone-specific alkaline phosphatase [BALP]), or bone matrix proteins [osteocalcin]. Among individuals not receiving osteoporosis treatment, resorption and formation markers are tightly linked and highly correlated (r = 0.6-0.8). Significant biological variability was reported in the past, but these issues have been greatly improved with automated assays and attention to pre-analytical and analytical factors that are known to influence bone turnover marker levels. Bone turnover markers are not useful in the diagnosis of osteoporosis, the individual prediction of bone loss, fracture, or rare complications, or in the selection of pharmacological treatment. Despite remaining issues with reference intervals and assays harmonization, bone turnover markers have proven to be useful in elucidating the pharmacodynamics and effectiveness of osteoporosis medications in clinical trials. As an alternative to BMD testing, BTMs may be useful to monitor osteoporosis therapies.

The Role of PINP in Diagnosis and Management of Metabolic Bone Disease.

Serum procollagen type I N-propeptide (PINP) is designated the reference marker of bone formation in osteoporosis; the reference marker for resorption is C-terminal telopeptide of type I collagen (CTX). PINP has very low circadian and biological variation, is not affected by food intake, and is very stable in serum after venepuncture. The two automated commercial assays for PINP provide similar results in subjects with normal renal function, allowing reference intervals to be used interchangeably. Bone turnover markers (BTM) are currently not recommended for fracture risk assessment and therefore not included in fracture risk calculators. In the management of osteoporosis, the main utility of BTM including PINP is for monitoring therapy, both antiresorptive as well as anabolic agents; monitoring is thought to help improve adherence. PINP as well as CTX may also be used in assessing offset of drug action following a pause in bisphosphonate therapy, to help decide when to re-instate therapy, or following cessation of denosumab therapy to assess efficacy of follow-on bisphosphonate therapy. PINP may also be used in the diagnosis of Paget's disease of bone as well as in monitoring response to therapy and for recurrence. Although BTM other than bone alkaline phosphatase are currently not recommended for use in metabolic bone disease of chronic kidney disease, PINP measured by assays specific to the intact molecule has potential in this condition. Further studies are needed to examine this area, as well as in malignant bone disease.

Recommendations on the measurement and the clinical use of vitamin D metabolites and vitamin D binding protein - A position paper from the IFCC Committee on bone metabolism.

Vitamin D, an important hormone with a central role in calcium and phosphate homeostasis, is required for bone and muscle development as well as preservation of musculoskeletal function. The most abundant vitamin D metabolite is 25-hydroxyvitamin D [25(OH)D], which is currently considered the best marker to evaluate overall vitamin D status. 25(OH)D is therefore the most commonly measured metabolite in clinical practice. However, several other metabolites, although not broadly measured, are useful in certain clinical situations. Vitamin D and all its metabolites are circulating in blood bound to vitamin D binding protein, (VDBP). This highly polymorphic protein is not only the major transport protein which, along with albumin, binds over 99% of the circulating vitamin D metabolites, but also participates in the transport of the 25(OH)D into the cell via a megalin/cubilin complex. The accurate measurement of 25(OH)D has proved a difficult task. Although a reference method and standardization program are available for 25(OH)D, the other vitamin D metabolites still lack this. Interpretation of results, creation of clinical supplementation, and generation of therapeutic guidelines require not only accurate measurements of vitamin D metabolites, but also the accurate measurements of several other "molecules" related with bone metabolism. IFCC understood this priority and a committee has been established with the task to support and continue the standardization processes of vitamin D metabolites along with other bone-related biomarkers. In this review, we present the position of this IFCC Committee on Bone Metabolism on the latest developments concerning the measurement and standardization of vitamin D metabolites and its binding protein, as well as clinical indications for their measurement and interpretation of the results.

Analytical considerations and plans to standardize or harmonize assays for the reference bone turnover markers PINP and ß-CTX in blood.

Procollagen type I N-propeptide (PINP) and the C-terminal telopeptide of type I collagen (ß-CTX) in blood have been designated as reference bone turnover markers in osteoporosis by the International Osteoporosis Foundation (IOF) and International Federation of Clinical Chemistry and Laboratory Medicine (IFCC). The IFCC Committee on Bone Metabolism (C-BM) has examined current commercial assays and performed a multicentre study to examine the agreement between assays for PINP and ß-CTX in serum and plasma. The results of these studies will inform our work towards the harmonization of PINP assays and the standardization of ß-CTX assays in blood, with the development of common calibrators and reference measurement procedures in collaboration with the reagent manufacturing industry. Successful achievement of these goals will help develop universally acceptable practice guidelines for the management of osteoporosis with the inclusion of common reference intervals and treatment targets for PINP and ß-CTX.

Short- and long-term biological variation of cardiac troponin I in healthy individuals, and patients with end-stage renal failure requiring haemodialysis or cardiomyopathy.

Objectives High-sensitivity (hs) cardiac troponin (cTn) assays can quantitate small fluctuations in cTn concentration. Determining biological variation allows calculation of reference change values (RCV), to define significant changes. We assessed the short- and long-term biological variation of cardiac troponin I (cTnI) in healthy individuals and patients with renal failure requiring haemodialysis or cardiomyopathy. Methods Plasma samples were collected hourly for 4 h and weekly for seven further weeks from 20 healthy individuals, 9 renal failure patients and 20 cardiomyopathy patients. Pre- and post-haemodialysis samples were collected weekly for 7 weeks. Samples were analysed using a hs-cTnI assay (Abbott Alinity ci-series). Within-subject biological variation (CVI), analytical variation (CVA) and between-subject biological variation (CVG) was used to calculate RCVs and index of individuality (II). Results For healthy individuals, CVI, CVA, CVG, RCV and II values were 8.8, 14.0, 43.1, 45.8% and 0.38 respectively for short-term, and 41.4, 14.0, 25.8, 121.0% and 1.69 for long-term. For renal failure patients, these were 2.6, 5.8, 50.5, 17.6% and 0.30 respectively for short-term, and 19.1, 5.8, 11.2, 55.2% and 1.78 for long-term. For cardiomyopathy patients, these were 4.2, 10.0, 65.9, 30.0% and 0.16 respectively for short-term, and 17.5, 10.0, 63.1, 55.8% and 0.32 for long-term. Mean cTnI concentration was lower post-haemodialysis (15.2 vs. 17.8 ng/L, p < 0.0001), with a 16.9% mean relative change. Conclusions The biological variation of cTnI is similar between end-stage renal failure and cardiomyopathy patients, but proportionately greater in well-selected healthy individuals with very low baseline cTnI concentrations.

High-Sensitivity Cardiac Troponin I Improves Cardiovascular Risk Prediction in Older Men: HIMS (The Health in Men Study).

Background The Framingham Risk Score estimates the 10-year risk of cardiovascular events. However, it performs poorly in older adults. We evaluated the incremental benefit of adding high-sensitivity cardiac troponin I (hs-cTnI) to the Framingham Risk Score. Methods and Results The HIMS (Health in Men Study) is a cohort study of community-dwelling men aged 70 to 89 years in Western Australia. Participants were identified from the electoral roll, with a subset undergoing plasma analysis. Hs- cTnI (Abbott Architect i2000 SR ) was measured in 1151 men without prior cardiovascular disease. The Western Australia Data Linkage System was used to identify incident cardiovascular events. After 10 years of follow-up, 252 men (22%) had a cardiovascular event ( CVE +) and 899 did not (CVE-). The Framingham Risk Score placed 148 (59%) CVE + and 415 (46%) CVE- in the high-risk category. In CVE - men, adding hs- cTnI affected the risk categories of 244 (27.2%) men, with 64.8% appropriately reclassified to a lower and 35.2% to a higher category, which decreased the number of high-risk men in the CVE- to 39%. In CVE + men, adding hs- cTnI affected the risk categories of 61 (24.2%), with 50.8% appropriately reclassified to a higher and 49.2% to a lower category and 82.5% remaining above the 15% risk treatment threshold. The net reclassification index was 0.305 ( P<0.001). Adding hs- cTnI increased the C-statistic modestly from 0.588 (95% CI , 0.552-0.624) to 0.624 (95% CI , 0.589-0.659) and improved model fit (likelihood ratio test, P<0.001). Conclusions Adding hs- cTnI to the Framingham Risk Score provided incremental prognostic benefit in older men, especially aiding reclassification of individuals into a lower risk category.

Improved technical success and radiation safety of adrenal vein sampling using rapid, semi-quantitative point-of-care cortisol measurement.

Objective Primary aldosteronism is a curable cause of hypertension which can be treated surgically or medically depending on the findings of adrenal vein sampling studies. Adrenal vein sampling studies are technically demanding with a high failure rate in many centres. The use of intraprocedural cortisol measurement could improve the success rates of adrenal vein sampling but may be impracticable due to cost and effects on procedural duration. Design Retrospective review of the results of adrenal vein sampling procedures since commencement of point-of-care cortisol measurement using a novel single-use semi-quantitative measuring device for cortisol, the adrenal vein sampling Accuracy Kit. MEASUREMENTS: Success rate and complications of adrenal vein sampling procedures before and after use of the adrenal vein sampling Accuracy Kit. Routine use of the adrenal vein sampling Accuracy Kit device for intraprocedural measurement of cortisol commenced in 2016. Results Technical success rate of adrenal vein sampling increased from 63% of 99 procedures to 90% of 48 procedures ( P = 0.0007) after implementation of the adrenal vein sampling Accuracy Kit. Failure of right adrenal vein cannulation was the main reason for an unsuccessful study. Radiation dose decreased from 34.2 Gy.cm2 (interquartile range, 15.8-85.9) to 15.7 Gy.cm2 (6.9-47.3) ( P = 0.009). No complications were noted, and implementation costs were minimal. Conclusions Point-of-care cortisol measurement during adrenal vein sampling improved cannulation success rates and reduced radiation exposure. The use of the adrenal vein sampling Accuracy Kit is now standard practice at our centre.

Faecal Calprotectin.

Calprotectin is a calcium- and zinc-binding protein of the S-100 protein family which is mainly found within neutrophils and throughout the human body. The presence of calprotectin in faeces is a consequence of neutrophil migration into the gastrointestinal tissue due to an inflammatory process. Faecal calprotectin concentrations demonstrate good correlation with intestinal inflammation and faecal calprotectin is used as a biomarker in gastrointestinal disorders. Faecal calprotectin is a very sensitive marker for inflammation in the gastrointestinal tract, and useful for the differentiation of inflammatory bowel disease (IBD) from irritable bowel syndrome (IBS). Faecal calprotectin is used for the diagnosis, monitoring disease activity, treatment guidance and prediction of disease relapse and post-operative recurrence in IBD. There may also potentially be a role for faecal calprotectin in the management of infectious gastroenteritis, acute appendicitis, peptic ulcer disease, cystic fibrosis, coeliac disease, transplant rejection and graft versus host disease. Further studies are needed to confirm its utility in these conditions. Analysis of faecal calprotectin consists of an extraction step followed by quantification by immunoassay. Over the past few decades, several assays and extraction devices including point-of-care methods have been introduced by manufacturers. The manufacturer-quoted cut-off values for different faecal calprotectin assays are generally similar. However, the sensitivities and specificities at a given cut-off, and therefore the optimum cut-off values, are different between assays. A reference standard for calprotectin is lacking. Therefore, assay standardisation is required for more accurate and traceable test results for faecal calprotectin.

Measurement and Clinical Utility of ßCTX in Serum and Plasma.

Biochemical markers of bone turnover (BTM) are released during bone remodeling and can be measured in blood or urine as noninvasive surrogate markers for the bone remodeling rate. The C-terminal cross-linked telopeptide of type I collagen (ßCTX) is released during bone resorption and is specific to bone tissue. Assays have been developed to measure ßCTX in blood and in urine; most current use of ßCTX measurement for research and in clinical practice is performed on a blood sample. Method-specific differences for serum and plasma ßCTX have led to initiatives to standardize or harmonize ßCTX commercial assays. ßCTX demonstrates significant biological variation due to circadian rhythm and effect of food which can be minimized by standardized sample collection in the fasting state in the morning. While ßCTX predicts fracture risk independent of bone mineral density, lack of data has precluded its inclusion in fracture risk calculators. The changes seen in ßCTX with antiresorptive therapies have been well characterized and this has led to its widespread use for monitoring therapy in osteoporosis. However, more fracture-based data on appropriate treatment goals for monitoring need to be developed. Evidence is lacking for the use of ßCTX in managing "drug holidays" of bisphosphonate treatment in osteoporosis or risk stratifying those at increased risk of developing osteonecrosis of the jaw. ßCTX is useful as an adjunct to imaging techniques for the diagnosis of Paget's disease of bone and for monitoring therapy and detecting recurrence. ßCTX also shows promise in the management of metastatic bone disease.

Clinical Utility and Measurement of Procalcitonin.

Procalcitonin (PCT), regarded as a biomarker specific for bacterial infections, is used in a variety of clinical settings including primary care, emergency department and intensive care. PCT measurement aids in the diagnosis of sepsis and to guide and monitor antibiotic therapy. This article gives a brief overview of PCT and its use in guiding antibiotic therapy in various clinical settings, as well as its limitations. PCT performance in comparison with other biomarkers of infection in particular CRP is also reviewed. Owing to its greater availability, CRP has been widely used as a biomarker of infection and sepsis. PCT is often reported to be more superior to CRP, being more specific for sepsis and bacterial infection. PCT starts to rise earlier and returns to normal concentration more rapidly than CRP, allowing for an earlier diagnosis and better monitoring of disease progression.

The use of biochemical markers of bone turnover in the clinical management of primary and secondary osteoporosis.

The purpose of the present study was to examine of the current role of bone turnover markers (BTMs) in the management of osteoporosis. Perusal of the literature examines the available evidence for the utility of BTMs for decision to treat and for the monitoring of treatment for osteoporosis. There is no evidence for the use of BTMs for fracture risk calculation, decision to treat or for treatment selection. A very abnormal BTM value may be a clue to the presence of bone pathology other than uncomplicated osteoporosis. Whilst changes to BTMs following various osteoporosis treatments are well defined, their utility in monitoring individual patients has been less well established. Some fracture outcome-based data exist for the use of u-NTX target of <21 nmol BCE/mmol for antiresorptive therapy; the equivalent s-CTX level is ~250 ng/L. Suboptimal BTM response to treatment may indicate non-compliance or the presence of secondary causes of osteoporosis which may need addressing. Studies are needed to establish treatment targets based on fracture outcomes for commonly used BTMs for each established osteoporosis therapy.

25-Hydroxyvitamin D C3-epimer is universally present in neonatal Western Australian samples but is unlikely to contribute to diagnostic misclassification.

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.

Is vitamin D testing at a tertiary referral hospital consistent with guideline recommendations?

To determine if 25 hydroxyvitamin D (25OHD) testing at our tertiary referral hospital is consistent with guideline recommendations concerning the clinical indications for testing, the timing of repeat testing and utilisation of the test result, we conducted a retrospective audit of electronic laboratory and patient case records. We included adult inpatients and outpatients who had serum 25OHD measured during a randomly selected one-week audit period and who had patient case records available for detailed review. The audit sample comprised 184 serum 25OHD measurements (134 initial and 50 repeat tests). There were 81 (60%) initial and 15 (30%) repeat tests [96 (52%) overall] that were consistent with guideline recommendations concerning clinical indication, timing of repeat testing and utilisation of result. Almost half the 25 hydroxyvitamin D tests audited were potentially unnecessary and/or not utilised clinically. Improved adherence to guideline recommendations for 25 hydroxyvitamin D testing, utilisation of test results and enforcement of new indications for testing due to be introduced by Medicare Australia could result in significant cost savings without adversely affecting patient outcomes.

Comparison of results from commercial assays for plasma CTX: The need for harmonization.

INTRODUCTION: Plasma C-terminal telopeptide of type I collagen (CTX) is the nominated reference bone resorption marker. We set out to test the agreement of patients' results between the available plasma CTX assays. METHODS: Samples were collected from patients attending tertiary hospitals and clinics for investigation and management of metabolic bone disease. Plasma (EDTA) samples were collected from fasted patients between 7.00 am and 11.00 am, divided into three portions and stored at -20°C until analysis. Plasma CTX was measured by enzyme-linked immunosorbent assay (ELISA) (Immunodiagnostic Systems plc), E170 (Roche Diagnostics) and IDS-iSYS (Immunodiagnostic Systems plc) methods. Agreement of patient sample results was assessed by Passing and Bablok regression. Commutability of the calibrators in each kit was assessed by assaying each calibrator in the alternate methods and comparing the observed results with those expected based on the relevant patients' samples method comparison; ±8.1% was set as the criterion for commutablity. RESULTS: 161 specimens were analysed. Regression parameters (slope, intercept) were 0.788, 0.2 ng/L for Roche vs ELISA, 1.266 and -109 ng/L for iSYS vs ELISA and 1.605 and -109 ng/L for iSYS vs Roche. Only the ELISA calibrator assayed in the Roche assay gave a result within 8.1% of the expected value. CONCLUSIONS: There is significant disagreement between the results generated for patient samples by the 3 CTX assays and limited commutability of the currently supplied calibrator materials between assays. Harmonization of the results from the different assays would greatly enhance the value of CTX as the reference bone resorption marker.

Reference intervals for bone turnover markers and their association with incident hip fractures in older men: the Health in Men study.

CONTEXT: Reference intervals for bone turnover markers (BTMs) and relationships between BTM and fracture risk in older men are not well characterized. OBJECTIVE: The purpose of this article was to determine the reference intervals for serum total osteocalcin (tOC), undercarboxylated osteocalcin (ucOC), N-terminal propeptide of type I collagen (PINP), and collagen type I C-terminal cross-linked telopeptide (CTX-I) in healthy older men and to explore factors associated with BTMs, including hip fracture risk. PARTICIPANTS AND SETTING: We studied a population-based cohort of 4248 men aged 70 to 89 years, 4008 of whom had serum samples available for analysis. INTERVENTIONS: Morning blood samples were collected at the study visit. Comorbid conditions were assessed by questionnaire. The reference sample comprised fasting men (n = 298, median age 75.3 years [interquartile range 73.9-78.1 years) reporting excellent or very good health, without a history of diabetes, cardiovascular disease, cancer, depression, or dementia. MAIN OUTCOME MEASURES: Serum tOC, PINP, and CTX-I were estimated by automated electrochemiluminescence immunoassays, ucOC was estimated using hydroxyapatite binding, and incident hip fractures were captured from hospital admission data. RESULTS: Reference intervals for tOC, ucOC, PINP, and CTX-I were 10.2 to 41.0, 5.2 to 21.9, 18 to 129 µg/L, and 117 to 740 ng/L, respectively. tOC, ucOC and CTX-I were associated with hip fracture incidence, but after adjustment for other risk factors only tOC remained significantly associated. CONCLUSIONS: Reference intervals for BTMs in older men have been defined. tOC may be more informative for hip fracture risk in older men than CTX-I and PINP. Further studies are needed to clarify the utility of BTM reference intervals in the management of aging men at risk of osteoporosis.

Anatomy and history of an external quality assessment program for interpretative comments in clinical biochemistry.

The provision of clinical interpretation of results, either verbally or in the printed report, may be considered an integral part of clinical biochemistry diagnostic service. Proficiency testing or external quality assessment (EQA) of such activity may be useful in education, training, continuing professional development and ensuring the quality of such service. Details of the Patient Report Comments Program (RPCProgram) developed by the Royal College of Pathologists of Australasia (RCPA) Chemical Pathology Quality Assurance Programs Pty Ltd (QAP) is described in this review. The program is aimed at pathologists, clinical scientists and trainees. Registered participants are provided a report with case details and a set of clinical biochemistry results at monthly intervals and submit an interpretative comment for the report. Comments received are broken up into components that are translated into common key phrases. An expert panel evaluates the key phrases, classifies them according to appropriateness and drafts a suggested comment, a case summary and a rationale, which are included in a summary report returned to participants. There is considerable diversity in the quality of interpretative comments received from participants of the PRCProgram. The primary purpose of EQA of interpretative commenting is educational self-assessment, and they are recognized as a continuing professional development activity. Whilst there is some evidence for the utility of interpretative comments in improving patient outcomes, evidence for the utility of EQA in improving quality of comments is awaited.