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Biomedical subjects

Peter E Hickman

Publications and source records attributed to Peter E Hickman.

14 recordsLinked to original sources

Over-reporting significant figures--a significant problem?

BACKGROUND: Excessive use of significant figures in numerical data gives a spurious impression of laboratory imprecision to clinicians. We describe reporting practices in 24 Asia-Pacific laboratories, assess whether these reporting formats and those used in the literature can be justified based on actual laboratory performance and outline how to choose the appropriate number of significant places. METHODS: Thirty-two laboratories in Asia-Pacific were surveyed as to their reporting practices for serum creatinine, ferritin, sodium and TSH. Imprecision data from the General Serum Chemistry program from the RCPA-AACB Quality Assurance Program (QAP) were used to assess whether the reporting unit magnitude implicitly suggested in Tietz, the RCPA Manual and the General Serum Chemistry program itself was justified. RESULTS: There was a 75% response rate to the survey, with laboratories generally reporting data using unjustifiable deciles. Unit sizes from the RCPA manual, Tietz and the RCPA-AACB QAP were not justified by the majority of laboratories in the RCPA-AACB QAP. CONCLUSIONS: The reporting unit size used by many laboratories is not justified by present laboratory performance using a 95% probability level. A consensus on appropriate reporting unit size is needed to encourage laboratories to change their present reporting formats.

Australia↗

Correction and reporting of potassium results in haemolysed samples.

BACKGROUND: Potassium is usually the most important analyte affected by in vitro haemolysis and the result obtained may falsely indicate or disguise a life-threatening abnormality and so give rise to inappropriate treatment. The purpose of the study was to provide a solution to the problem of reporting potassium on haemolysed samples, taking into account both clinical needs and analytical concerns (inter-individual and inter-sample variability). METHODS: Using a new procedure that mimics the collection process in an actual clinical setting, haemolysed samples were prepared from 41 volunteers with a range of inter-individual factors - haemoglobin 80-173 g/L, red blood cells 2.42-6.77 x 10(12)/L, leucocytes 3.0-306 x 10(9) /L and platelets 31-710 x 10(9)/L - in order to develop a more accurate correction equation using a haemolytic index (HI) corresponding to g Hb/L in plasma. RESULTS: The mean (range) potassium increase was 0.0036 mmol/L (0.0029-0.0053 mmol/L) per unit HI. The following equation was developed to estimate potassium increase per HI, in order to compensate approximately for potassium leakage in haemolysed samples: Corrected K+ = Measured K+ -(HI x 0.004). CONCLUSION: The balanced solution is this: instead of reporting the post-haemolysis corrected potassium result a qualitative comment is given, indicating the likely range of the potassium concentration. If the potassium result is in a critically low or high range, it is communicated promptly to the requesting clinician.

Blood Specimen Collection↗

Area-under-the-curve monitoring of prednisolone for dose optimization in a stable renal transplant population.

BACKGROUND: Renal transplant recipients were noted to appear cushingoid while on low doses of steroid as part of a triple therapy immunosuppression of cyclosporin A (CsA), prednisolone, and azathioprine. METHODS: The study group comprised adult renal transplant recipients with stable graft function who had received their renal allograft a minimum of 1 year previously (43 studies undertaken in 22 men and 20 women) with median daily prednisone dose of 7 mg (range 3-10). The control group was healthy nontransplant subjects [median dose 10 mg (10-30)]. Prednisolone bioavailability was measured using a limited 6-hour area under the curve (AUC), with prednisolone measured using specific HPLC assay. RESULTS: The median prednisolone AUC/mg dose for all transplant recipients was significantly greater than the control group by approximately 50% (316 nmol x h/L/mg prednisolone versus 218). AUC was significantly higher in female recipients (median 415 versus 297 for men) and in recipients receiving cyclosporin (348 versus 285). The highest AUC was in women on estrogen supplements who were receiving cyclosporin (median 595). A significantly higher proportion of patients on triple therapy had steroid side effects compared with those on steroid and azathioprine (17/27 versus 4/15), more women than men had side effects (14/16 versus 7/22), and the AUC/mg prednisone was greater in those with side effects than without (median 377 versus 288 nmol x h/L/mg). DISCUSSION: The results are consistent with the hypothesis that CsA increases the bioavailability of prednisolone, most likely through inhibition of P-glycoprotein. The increased exposure to steroid increased the side-effect profile of steroids in the majority of patients. Because the major contributor to AUC is the maximum postdose concentration, it may be possible to use single-point monitoring (2 hours postdose) for routine clinical studies.

Adolescent↗

Objective determination of appropriate reporting intervals.

BACKGROUND: The reporting interval is the incremental value chosen in reporting analyte concentration. Reporting intervals for different analytes are often inappropriately narrow, when analytical imprecision and biological variability are considered. METHODS: We have used statistical techniques to determine intervals for individual analytes at which there is 50% or 95% confidence that two results are analytically different, and compared these with the reporting intervals in use for a range of general chemistry analytes and analytes usually measured by immunoassay. RESULTS: No analytes met the criteria for 95% confidence that the results are analytically different. Even at the 50% confidence level, 24 of 46 analytes failed at all concentrations examined. For some analytes, particularly hormones at high concentration, the reporting interval increment should be increased by a factor of at least ten. CONCLUSIONS: The majority of analytes are inappropriately reported when analytical precision alone is considered. The concept of the 'uncertainty of measurement' has not been adequately addressed. A consensus should be reached and implemented on appropriate reporting intervals for all analytes.

Chemistry, Clinical↗

Quality assessment of interpretative commenting in clinical chemistry.

BACKGROUND: Clinical interpretation of laboratory results is an integral part of clinical chemistry. However, the performance goals for assessing interpretative commenting in this discipline have not been as well established as for the quality of analytical requirements. METHODS: We present a review of the 10 case reports circulated in the 2002 Patient Report Comments Program by the Royal College of Pathologists of Australasia (RCPA) and the Australasian Association of Clinical Biochemists Chemical Pathology Group of RCPA-Quality Assurance Programs Pty Ltd. Participants were expected to add an interpretative comment to a set of results accompanied by brief clinical details. Comments received were broken down into components that were translated into key phrases. An expert panel evaluated the appropriateness of the key phrases and proposed a suggested composite comment. A case summary/rationale was also returned to participants. RESULTS: There was considerable diversity in the range of interpretative comments received for each case report. Although the majority of comments received were felt to be acceptable by the expert panel, some comments were felt to be inappropriate, misleading, or in a few instances, dangerous. CONCLUSION: The golden rule in medicine is "do no harm". Although there is no objective evidence that interpretive comments help to improve patient outcomes, if comments are added to reports it is important that they reflect accepted practice and current guidelines. It is of concern that a large proportion of comments returned were considered to be inappropriate and/or misleading. The Patient Report Comments Program has highlighted the need to consider limiting commenting to persons with clear expertise.

Clinical Chemistry Tests↗

Practical considerations for the measurement of free light chains in serum.

BACKGROUND: A new immunoassay for free light chain measurements has been reported to be useful for the diagnosis and monitoring of monoclonal light chain diseases and nonsecretory myeloma. We describe experience with and some potential pitfalls of the assay. METHODS: The assay was assessed for precision, sample type and stability, recovery, and harmonization of results between two analyzers on which the reagents are used. Free-light-chain concentrations were measured in healthy individuals (to determine biological variation), patients with monoclonal gammopathy of undetermined significance, myeloma patients after autologous stem cell transplants, and patients with renal disease. RESULTS: Analytical imprecision (CV) was 6-11% for kappa and lambda free-light-chain measurement and 16% for the calculated kappa/lambda ratio. Biological variation was generally insignificant compared with analytical variation. Despite the same reagent source, values were not completely harmonized between assay systems and may produce discordant free-light-chain ratios. In some patients with clinically stable myeloma, or post transplantation, or with monoclonal gammopathy of undetermined significance, free-light-chain concentration and ratio were within the population reference interval despite the presence of monoclonal intact immunoglobulin in serum. In other patients with monoclonal gammopathy of undetermined significance, values were abnormal although there was no clinical evidence of progression to multiple myeloma. CONCLUSIONS: The use of free-light-chain measurements alone cannot differentiate some groups of patients with monoclonal gammopathy from healthy individuals. As with the introduction of any new test, it is essential that more scientific data about use of this assay in different subject groups are available so that results can be interpreted with clinical certainty.

Humans↗

A discussion of cases in the 2001 RCPA-AQAP Chemical Pathology Case Report Comments Program.

AIM: We present a descriptive analysis of the 10 case reports distributed in the Royal College of Pathologists of Australasia (RCPA) and the Australasian Association of Clinical Biochemists (AACB) Chemical Pathology Patient Report Comments Program to assess the quality of interpretative commenting in clinical biochemistry in 2001. METHOD: Participants were asked to comment on a given set of biochemistry results attached with brief clinical details. All responses received were translated into key phrases and graphically presented on a histogram. An expert panel was asked to evaluate the appropriateness of the key phrases and to propose a suggested composite comment. RESULTS: While the majority of comments received were felt to be acceptable by the expert panel, some comments were felt to be inappropriate or misleading. As comments on laboratory reports may affect clinical management of patients, it is important that these comments reflect accepted practice and current guidelines. CONCLUSION: The Patient Report Comments Program may play an important role in continuing education and possibly in quality assurance of interpretative commenting.

Adult↗

Screening for hemochromatosis.

BACKGROUND: Hereditary hemochromatosis is the most common autosomal recessive disorder in populations of northern European descent. ISSUES: Many experts consider hemochromatosis to be an almost ideal disease for population screening because it essentially fulfills almost all the criteria for screening proposed by the WHO. However, others disagree and suggest that more data are required particularly with regard to the natural history and penetrance of the disease. There is also disagreement about the best diagnostic/screening test for the disease and the performance of these tests in the context of screening. Other concerns are the variability and lack of standardization in screening test measurements, the selection of screening threshold values and the identification of false positive cases. The advent of a genetic test for the condition has brought other worries with regard to informed consent and the ethical, legal and social implications of screening particularly in relation to medical and general discrimination. Other important issues include compliance, cost effectiveness and the evidence that screening has lessened the burden of disease in the community. CONCLUSIONS: At the present time, we believe that further data regarding both the exact disease burden and the outcomes of screening studies particularly in the general community are required before widespread population screening is introduced.

Adult↗