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Improving the clinical utility of antinuclear antibody reporting by incorporating likelihood ratios in interpretative comments
PATHOLOGY UPDATE 2009 ABSTRACT PUBLICATION
uncommon, especially in high stage disease. Metastatic disease is present in 25% of cases at presentation. Metastasis is generally via the haematogenous route with the most common sites for metastases being the lung. Other sites include pleura, other bones including skull, marrow, CNS and lymph nodes. To the best of our knowledge, there has been only one previous report of renal metastasis of Ewing’s sarcoma. That case was not substantiated by CD99 immunohistochemistry, molecular or cytogenetic evidence. Late metastases are unusual with most recurrences occurring in the first 2 years. We present a rare case of Ewing’s sarcoma which recurred after at least 9 years as metastatic disease in the kidney. The characteristic t(11;22) translocation was demonstrated and a positive immunohistochemical reaction with CD99 was observed.
RCPA Quality Assurance Programs Pty Ltd Presentations EVALUATION OF ACETAMINOPHEN RECOVERY IN HUMAN SERUM Said N Al-Azri, Nimalie J Perera, Jennifer C Burns, Peter M Stewart Department of Clinical Biochemistry, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia Background: Acetaminophen toxicity can lead to hepatic and renal damage. Early and accurate measurement of acetaminophen is critical for the management of patients. The Royal College of Pathologists Quality Assurance Program (RCPA-QAP) end of cycle report for acetaminophen shows a significant negative bias (18%) when compared to the median of all values and methods. This may have serious implications for patient samples if the true values are underestimated by the same extent. The aim of this study is to evaluate whether this bias is real. Methods: A series of samples was prepared using an acetaminophen spiked human serum pool diluted with non-spiked matching serum across the stated measurement range and measured on the Roche Modular PPE by enzymatic assay. Recoveries were calculated and the values at the decision points for hepatic and renal toxicity were evaluated (2001300 mmol/L). Results: Ten levels of acetaminophen were examined. The bias across the concentration range was B2% and was 0% at the critical decision points. Conclusion: The negative bias evident from EQAP measurements is absent when tested in human serum pools. This indicates that acetaminophen is accurately measured in the Modular PPE and is fit for purpose for monitoring of acetaminophen toxicity. References: Roche Diagnostics. Acetaminophen Package Insert, 200612. RCPA Chemical Pathology QAP. End of Cycle Report for Paracetamol. May 2008. Burtis CA, Ashwood ER, Bruns DE, editors. Tietz Fundamentals of Clinical Chemistry. 6th ed. St Louis: Saunders, 2008; 56970.
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IMPROVING THE CLINICAL UTILITY OF ANTINUCLEAR ANTIBODY REPORTING BY INCORPORATING LIKELIHOOD RATIOS IN INTERPRETATIVE COMMENTS Mahmood Al Kindi, John Bahnisch, John Cassidy, Dianne Gilham, Pravin Hissaria Institute of Medical and Veterinary Science/SA Pathology, Adelaide, South Australia Background: The interpretation of antinuclear antibody (ANA) test results is complex with current reporting adding little useful clinical information. Aims: To improve the quality of ANA interpretative comments through the use of likelihood ratios (LRs) at different ANA titres for diagnosing systemic rheumatic diseases. Currently, no other laboratory in Australia implements this tool. Methods: A total of 369 consecutive blood samples referred for ANA testing over a 1-week period were simultaneously assessed for extractable nuclear antigens (ENA) and dsDNA. The ANA antibodies were screened using Hep 2000 (Immunoconcepts). ENA antibodies were screened using an in-house counterimmunoelectrophoresis (CIE) method and characterised by FIDIS (Biomedical Diagnostic). Anti-dsDNA antibodies were measured by the FARR assay (Amerlex commercial kits). All commercial assays were performed according to the manufacturers’ instructions. Results: Sixty-three patients (17%) were positive for ANA testing, 51(81%) female and 12 (19%) male. ANA testing was positive in 18.3% (37/202) of the age group ]50 years and in 15.5% (26/167) of the age group B50 years. ENA testing was positive in 5.9% (12/ 202) of the age group ]50 years and in 5.3% (9/167) of the age group B50 years. The different patterns seen were, 35 (55.5%) homogenous, 19 (30.2%) speckled, five (7.9%) SSA, three (4.7%) nucleolar and six (9.5%) other patterns (centromere and PCNA). ENA was positive in five patients (14%) with homogenous pattern, four (21%) with speckled and all the nucleolar, centromere and PCNA patterns. Hep 2000 screening detected 83.3% (5/6) of the SSA positive ENA. Positive dsDNA antibodies were reported in four (6.3%) ANA positive patients (63), and two (0.65%) in the ANA negative patients. The positive/negative likelihood ratios (LRs) of ANA at dilutions of 1/160, 1/640, 1/2560 were 6.4/0.15, 20/0.56 and 95/0.73, respectively. Conclusions: 1. A more effective method of interpreting ANA results is through LR which increases significantly with ANA positivity. The LR contrasts the proportion of individuals with and without systemic rheumatic diseases at a given level of ANA. It provides an independent measure of the post-test probability with the pre-test probability. 2. No significant difference in ANA and ENA positivity between both age groups (B50 and]50 years). 3. The correlation between ANA and ENA was more significant in nucleolar, centromere, PCNA and SSA patterns than in speckled and homogenous patterns.
INITIATIVES TO IMPROVE COMPLETION OF TRANSFUSION REQUEST FORMS IN ORDER TO HELP ENSURE APPROPRIATE USE OF TRANSFUSION L Al-Zadjali, S A Francis, S Meldrum, A Thomson Transfusion Laboratory, Royal North Shore Hospital, PaLMS, Sydney, New South Wales, Australia
uncommon, especially in high stage disease. Metastatic disease is present in 25% of cases at presentation. Metastasis is generally via the haematogenous route with the most common sites for metastases being the lung. Other sites include pleura, other bones including skull, marrow, CNS and lymph nodes. To the best of our knowledge, there has been only one previous report of renal metastasis of Ewing’s sarcoma. That case was not substantiated by CD99 immunohistochemistry, molecular or cytogenetic evidence. Late metastases are unusual with most recurrences occurring in the first 2 years. We present a rare case of Ewing’s sarcoma which recurred after at least 9 years as metastatic disease in the kidney. The characteristic t(11;22) translocation was demonstrated and a positive immunohistochemical reaction with CD99 was observed.
RCPA Quality Assurance Programs Pty Ltd Presentations EVALUATION OF ACETAMINOPHEN RECOVERY IN HUMAN SERUM Said N Al-Azri, Nimalie J Perera, Jennifer C Burns, Peter M Stewart Department of Clinical Biochemistry, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia Background: Acetaminophen toxicity can lead to hepatic and renal damage. Early and accurate measurement of acetaminophen is critical for the management of patients. The Royal College of Pathologists Quality Assurance Program (RCPA-QAP) end of cycle report for acetaminophen shows a significant negative bias (18%) when compared to the median of all values and methods. This may have serious implications for patient samples if the true values are underestimated by the same extent. The aim of this study is to evaluate whether this bias is real. Methods: A series of samples was prepared using an acetaminophen spiked human serum pool diluted with non-spiked matching serum across the stated measurement range and measured on the Roche Modular PPE by enzymatic assay. Recoveries were calculated and the values at the decision points for hepatic and renal toxicity were evaluated (2001300 mmol/L). Results: Ten levels of acetaminophen were examined. The bias across the concentration range was B2% and was 0% at the critical decision points. Conclusion: The negative bias evident from EQAP measurements is absent when tested in human serum pools. This indicates that acetaminophen is accurately measured in the Modular PPE and is fit for purpose for monitoring of acetaminophen toxicity. References: Roche Diagnostics. Acetaminophen Package Insert, 200612. RCPA Chemical Pathology QAP. End of Cycle Report for Paracetamol. May 2008. Burtis CA, Ashwood ER, Bruns DE, editors. Tietz Fundamentals of Clinical Chemistry. 6th ed. St Louis: Saunders, 2008; 56970.
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IMPROVING THE CLINICAL UTILITY OF ANTINUCLEAR ANTIBODY REPORTING BY INCORPORATING LIKELIHOOD RATIOS IN INTERPRETATIVE COMMENTS Mahmood Al Kindi, John Bahnisch, John Cassidy, Dianne Gilham, Pravin Hissaria Institute of Medical and Veterinary Science/SA Pathology, Adelaide, South Australia Background: The interpretation of antinuclear antibody (ANA) test results is complex with current reporting adding little useful clinical information. Aims: To improve the quality of ANA interpretative comments through the use of likelihood ratios (LRs) at different ANA titres for diagnosing systemic rheumatic diseases. Currently, no other laboratory in Australia implements this tool. Methods: A total of 369 consecutive blood samples referred for ANA testing over a 1-week period were simultaneously assessed for extractable nuclear antigens (ENA) and dsDNA. The ANA antibodies were screened using Hep 2000 (Immunoconcepts). ENA antibodies were screened using an in-house counterimmunoelectrophoresis (CIE) method and characterised by FIDIS (Biomedical Diagnostic). Anti-dsDNA antibodies were measured by the FARR assay (Amerlex commercial kits). All commercial assays were performed according to the manufacturers’ instructions. Results: Sixty-three patients (17%) were positive for ANA testing, 51(81%) female and 12 (19%) male. ANA testing was positive in 18.3% (37/202) of the age group ]50 years and in 15.5% (26/167) of the age group B50 years. ENA testing was positive in 5.9% (12/ 202) of the age group ]50 years and in 5.3% (9/167) of the age group B50 years. The different patterns seen were, 35 (55.5%) homogenous, 19 (30.2%) speckled, five (7.9%) SSA, three (4.7%) nucleolar and six (9.5%) other patterns (centromere and PCNA). ENA was positive in five patients (14%) with homogenous pattern, four (21%) with speckled and all the nucleolar, centromere and PCNA patterns. Hep 2000 screening detected 83.3% (5/6) of the SSA positive ENA. Positive dsDNA antibodies were reported in four (6.3%) ANA positive patients (63), and two (0.65%) in the ANA negative patients. The positive/negative likelihood ratios (LRs) of ANA at dilutions of 1/160, 1/640, 1/2560 were 6.4/0.15, 20/0.56 and 95/0.73, respectively. Conclusions: 1. A more effective method of interpreting ANA results is through LR which increases significantly with ANA positivity. The LR contrasts the proportion of individuals with and without systemic rheumatic diseases at a given level of ANA. It provides an independent measure of the post-test probability with the pre-test probability. 2. No significant difference in ANA and ENA positivity between both age groups (B50 and]50 years). 3. The correlation between ANA and ENA was more significant in nucleolar, centromere, PCNA and SSA patterns than in speckled and homogenous patterns.
INITIATIVES TO IMPROVE COMPLETION OF TRANSFUSION REQUEST FORMS IN ORDER TO HELP ENSURE APPROPRIATE USE OF TRANSFUSION L Al-Zadjali, S A Francis, S Meldrum, A Thomson Transfusion Laboratory, Royal North Shore Hospital, PaLMS, Sydney, New South Wales, Australia