Aetiologies and factors associated with poor clinical outcomes in rhabdomyolysis: a retrospective cohort study in an Australian trauma centre.

Rhabdomyolysis is a clinical syndrome with significant morbidity and mortality that occurs as a result of traumatic and non-traumatic aetiologies. Acute kidney injury, the need for dialysis, and death, can occur due to rhabdomyolysis. This study explores the aetiologies, clinical outcomes and associated factors for poor outcomes in a cohort of patients with rhabdomyolysis in a tertiary trauma centre in Australia.

Prevalence of hyperglycaemia without previously recognised diabetes mellitus in the emergency department and subsequent management: a retrospective cross-sectional study.

BACKGROUND: Australian hospital data on hyperglycaemia without previously known diabetes are lacking. AIMS: To determine the prevalence of hyperglycaemia without previously recognised diabetes among all patients screened in the emergency department (ED). Secondary aims are to describe the extent of haemoglobin A1c testing for evaluation of new diabetes, adequate glucose monitoring, treatment of significant hyperglycaemia and documented follow-up plans. METHODS: Patients presenting to ED at the Alfred (tertiary hospital in Melbourne) have undergone screening random plasma glucose (RPG) with their first plasma biochemistry since 2015. Of the 16 268 adults screened from July to December 2015, a retrospective, cross-sectional study was undertaken evaluating those with hyperglycaemia (RPG >7.8 mmol/L) but without previously recognised diabetes as determined from coding data. After patient records were reviewed to correct for coding errors, a nested cohort of 200 such patients were further evaluated. Glucose monitoring was deemed adequate if undertaken for ≥48 h. Significant hyperglycaemia (RPG >11 mmol/L) was considered appropriately treated if insulin/hypoglycaemic agents were prescribed. Documented follow-up plans were acceptable if found in the discharge summary. RESULTS: Among all patients screened, 1178 had hyperglycaemia without coded diabetes. After adjusting for coding errors, the prevalence was 5.2%. Within the nested cohort, only 7.5% had a follow-up haemoglobin A1c ordered, 9.5% underwent adequate glucose monitoring, 6.5% had appropriate treatment of significant hyperglycaemia and 2% had documentation of a follow-up plan. CONCLUSIONS: Hyperglycaemia without previously recognised diabetes is commonly seen and justifies ED screening. However, management of newly detected hyperglycaemia in these patients is suboptimal and requires improvement.

The Incidence and Significance of Raised Troponin Levels in Acute Burns.

The place and significance of troponin testing in acute burn injuries has not yet been established. The aims of this study were to determine the incidence and pattern of troponin testing within a large population of acute burn injuries and subsequently to determine the resultant clinical significance of the troponin test results. A retrospective analysis of all patients with acute burn admissions (n = 1,621 patients) to a busy tertiary adult burns center between July 2009 and July 2015. More than a third of our patients had at least one troponin test performed. Men, the elderly, and those with larger burns were more likely to be tested. The majority tested had the laboratory test done within 24 hours of admission. A positive troponin test strongly correlated with increased risk of acute cardiac complication and death, as did burns greater than 15% total body surface area (%TBSA) and age. Acute burns of ≥15% TBSA are associated with elevated troponin levels. Troponins should be tested in those ≥50 years old, with significant burns, and/or premorbid cardiac disease; positive results investigated as they affect cardiac and survival outcomes.

A comparison between high resolution serum protein electrophoresis and screening immunofixation for the detection of monoclonal gammopathies in serum.

BACKGROUND: There are a variety of initial laboratory tests or combinations of tests that can be performed when a monoclonal gammopathy is suspected including serum protein electrophoresis (SPEP), urine protein electrophoresis (UPEP), serum immunofixation (IFE) and serum free light chain assays. Some groups have recently used simplified "screening" IFE methods for the detection of monoclonal gammopathies leveraging the greater sensitivity of IFE over SPEP alone to improve the detection of monoclonal gammopathies. These screening techniques have been predominantly evaluated against lower resolution agarose gel electrophoresis techniques. METHODS: In this study we evaluated the diagnostic performance of the combined κ and λ light chain screening immunofixation (CLIF) in comparison to serum protein electrophoresis on a high-resolution (Sebia Hydragel 15 HR) agarose gel system. Each gel was interpreted by three adjudicators. A total of 156 patient samples were analysed. Adjudicated diagnoses based on the screening techniques were compared against the results of high resolution serum protein electrophoresis and high resolution standard immunofixation performed during routine laboratory operation. Where standard immunofixation was not performed a combination of a review of medical records, serum free light chains, UPEP and bone marrow aspirate and trephine and subsequent standard immunofixation and protein electrophoresis results where available were used to confirm the absence of a monoclonal gammopathy. RESULTS: In this cohort a total of 65 (41%) patients had a paraprotein confirmed by standard immunofixation. HR SPEP had a sensitivity and specificity of 95% and 85%, respectively, while CLIF had a sensitivity and specificity of 88% and 97%, respectively. CONCLUSIONS: Overall we found that high-resolution gel serum protein electrophoresis using a Sebia Hydragel 15 HR system was more sensitive than a screening immunofixation method (CLIF) for the detection of paraproteins in patient serum in this patient cohort. The drawback of the greater sensitivity of HR SPEP was a higher false positive rate requiring an increased utilisation of follow up immunofixation electrophoresis.

Impact of High-Sensitivity Troponin I Testing with Sex-Specific Cutoffs on the Diagnosis of Acute Myocardial Infarction.

BACKGROUND: High-sensitivity cardiac troponin I (hs-cTnI) assays show sex-dependent differences in the 99th percentile of healthy populations, with concentrations in women approximately 50% lower. The adoption of sex-specific cutoffs seems appropriate, although it is not yet clear what effect these will have on acute myocardial infarction (AMI) diagnosis and management. METHODS: We conducted a retrospective pre- and postchangeover analysis of troponin I testing in the 6 months before and after moving from the contemporary Abbott Architect TnI assay (cTnI) to hs-cTnI at 2 tertiary centers in Australia and New Zealand. The cTnI cutoff was 30 ng/L for both sexes, whereas a female-specific cutoff of 16 ng/L was adopted upon changeover to hsTnI. RESULTS: Changeover from the cTnI assay to the hs-cTnI assay increased the number of female patients with increased troponin I concentrations at both sites (from 29.7% to 34.9% and from 22.4% to 30.8%; P < 0.001). There was no statistically significant change in the number of men with increased concentrations in the same time period (P = 0.09). The increased percentage of women with increased troponin I was not associated with an increase in the number of women with AMI diagnoses at either center. Angiographic data available from 1 center showed no change in the percentage of angiograms performed in women. CONCLUSIONS: Although increasing the proportion of women with increased troponin I, adopting sex-specific cutoffs with the hs-cTnI assay did not lead to an increase in AMI diagnoses in females, or in the number of women undergoing angiography.

Towards optimising the provision of laboratory services for bone turnover markers.

Bone turnover markers (BTMs) are either secreted by osteoblasts during bone formation or released by degradation of the collagen matrix of bone during bone resorption, and may be measured in blood or urine to provide an estimate of the rate of bone remodelling. Increased bone remodelling rate is often associated with bone loss which can result in osteoporosis; however, lack of data preclude the inclusion of BTMs in fracture risk algorithms. The changes in BTMs following therapy for osteoporosis may be useful for monitoring. Serum procollagen type I amino-terminal propeptide (s-PINP) and serum carboxy-terminal cross-linking telopeptide of type I collagen (s-ßCTX) have been designated as reference standard markers of bone formation and resorption respectively in osteoporosis; further research is needed for their routine use in osteoporosis. BTMs are useful in diagnosing and monitoring Paget's disease of bone and other bone diseases associated with abnormal bone formation and/or resorption. Standardised patient preparation is required to mitigate the effect of biological variation, and appropriate sample handling and storage are important to minimise sample degradation. Significant inter-method differences exist for BTMs, and harmonisation of methods for the reference BTMs is being pursued. This will help develop universally accepted decision limits and treatment goals. Australian consensus reference intervals have been developed for some methods for s-PINP and s-ßCTX.

Harmonised Australian Reference Intervals for Serum PINP and CTX in Adults.

Bone turnover markers (BTMs) are classified as either formation or resorption markers. Their concentrations in blood or urine of adults are considered to reflect the rate of bone remodelling and may be of use in the management of patients with bone disease. Major inter-method differences exist for BTMs, and harmonisation of methods is currently being pursued at an international level. Based on published data, this article describes age- and sex-specific Australian consensus reference intervals for adults for serum procollagen type I amino-terminal propeptide (s-PINP) and serum ß-isomerised carboxy-terminal cross-linking telopeptide of type I collagen (s-CTX).

Change of HbA1c reporting to the new SI units.

An international consensus statement recommends that dual reporting of haemoglobin A (HbA(1c)) levels--in the current units (percentage) and Système International (SI) units (mmol/mol)--be used as an interim measure for a 2-year transition period before progressing towards the use of SI units only. This recommendation is supported by the Australasian Association of Clinical Biochemists, the Australian Diabetes Educators Association, the Australian Diabetes Society and the Royal College of Pathologists of Australasia. The SI units are a true measure of HbA(1c) and remove potential confusion between HbA(1c) values and blood glucose values.

B-type natriuretic peptide testing and the accuracy of heart failure diagnosis in the emergency department.

BACKGROUND: It is often difficult to diagnose heart failure (HF) accurately in patients presenting with dyspnea to the emergency department (ED). This study assessed whether B-type natriuretic peptide (BNP) testing in these patients improved the accuracy of HF diagnosis. METHODS AND RESULTS: Patients presenting to the Alfred and the Northern Hospital EDs with a chief complaint of dyspnea were enrolled prospectively from August 2005 to April 2007. Patients were randomly allocated to have BNP levels tested or not. The diagnostic gold standard for HF was determined by 1 cardiologist and 1 emergency or respiratory physician who, blinded to the BNP result, independently reviewed all available information. The ED diagnosis of HF in the non-BNP group showed a sensitivity, specificity, and accuracy of 65%, 92%, and 81%, respectively. The BNP group had a similar sensitivity, specificity, and accuracy of 66%, 90%, and 78%, respectively, for the diagnosis of HF in the ED. There was no significant difference between the BNP and non-BNP groups in any of the measures of diagnostic accuracy for HF. CONCLUSIONS: In the clinical setting of EDs, availability of BNP levels did not significantly improve the accuracy of a diagnosis of HF. Clinical Trial Registration- clinicaltrials.gov. Identifier: NCT00163709.

B-type natriuretic peptide testing, clinical outcomes, and health services use in emergency department patients with dyspnea: a randomized trial.

BACKGROUND: B-type natriuretic peptide (BNP) is used to diagnose heart failure, but the effects of using the test on all dyspneic patients is uncertain. OBJECTIVE: To assess whether BNP testing alters clinical outcomes and health services use of acutely dyspneic patients. DESIGN: Randomized, single-blind study. Patients were assigned to a treatment group through randomized numbers in a sealed envelope. Patients were blinded to the intervention, but clinicians and those who assessed trial outcomes were not. SETTING: 2 Australian teaching hospital emergency departments. PATIENTS: 612 consecutive patients who presented with acute severe dyspnea from August 2005 to March 2007. INTERVENTION: BNP testing (n = 306) or no testing (n = 306). MEASUREMENTS: Admission rates, length of stay, and emergency department medications (primary outcomes); mortality and readmission rates (secondary outcomes). RESULTS: There were no between-group differences in hospital admission rates (85.6% [BNP group] vs. 86.6% [control group]; difference, -1.0 percentage point [95% CI, -6.5 to 4.5 percentage points]; P = 0.73), length of admission (median, 4.4 days [interquartile range, 2 to 9 days] vs. 5.0 days [interquartile range, 2 to 9 days]; P = 0.94), or management of patients in the emergency department. Test discrimination was good (area under the receiver-operating characteristic curve, 0.87 [CI, 0.83 to 0.91]). Adverse events were not measured. LIMITATION: Most patients were very short of breath and required hospitalization; the findings might not apply for evaluating patients with milder degrees of breathlessness. CONCLUSION: Measurement of BNP in all emergency department patients with severe shortness of breath had no apparent effects on clinical outcomes or use of health services. The findings do not support routine use of BNP testing in all severely dyspneic patients in the emergency department. PRIMARY FUNDING SOURCE: Janssen-Cilag.

Procalcitonin for the clinical laboratory: a review.

Procalcitonin measurement has been claimed as a helpful marker in bacterial infection and sepsis. It has obtained FDA approval and is now widely marketed in the United States and Europe. This review summarises the current assays available, the evidence for its use and possible future applications of the assay.

Performance evaluation and subsequent clinical experience with the Abbott Automated Architect STAT Troponin-I assay.

BACKGROUND: Cardiac troponins are specific biochemical markers of myocardial injury used in the diagnosis of acute myocardial disease and cardiac risk stratification. To avoid misclassification of patients, troponin assays must demonstrate precision at the low end of the measuring range. We report our evaluation of the Architect STAT Troponin-I assay (Abbott Diagnostics), comparison of low-positive results with 2 other assays, and occurrence of heterophile antibody interference in the assay. METHODS: We assessed analytical performance on the ci8200 according to CLSI protocols, using quality-control and patient samples. Our healthy reference population included 480 blood donors. For correlation studies against the AxSYM first-generation cTnI (Abbott Diagnostics) and Access second-generation AccuTnI (Beckman Coulter) assays, we used 339 samples from hospital patients. RESULTS: The CV of the Architect STAT Troponin-I assay was 10% near the 99th percentile for the reference population (0.03 microg/L). Comparison with the AxSYM first-generation cTnI assay showed good correlation at higher concentrations, but better sensitivity of the Architect cTnI assay at low concentrations, which were clinically relevant as shown by review of patient histories. Correlation was good at the low end of the measuring range with the Access second-generation AccuTnI. Over the last 12 months we have identified 6 patients with heterophile antibodies causing positive interference. CONCLUSIONS: The Architect STAT Troponin-I assay provides highly sensitive measurement of cTnI with a CV of 10% near the upper limit of a reference population; however, heterophile antibodies can interfere with this assay.

Cardiac troponin I concentrations, but not electrocardiographic results, predict an extended hospital stay after coronary artery bypass graft surgery.

BACKGROUND: Cardiac damage in coronary artery graft (CABG) surgery is an important contributor to postoperative cardiac dysfunction and delayed hospital discharge. Currently, no simple method exists for its quantification. METHODS: In a prospective study of 300 patients having routine CABG surgery, we compared cardiac troponin I (cTnI) concentrations at 6 and 24 h after surgery with electrocardiographic (ECG) results as predictors of an extended postoperative stay in the intensive care unit (ICU) and in the hospital. We stratified outcome variables by tertiles of cTnI concentration and studied the significance of differences between outcome variables across tertiles. RESULTS: Multivariate analysis showed that 24-h cTnI is a significant predictor of increased postoperative ICU stay (P = 0.012) and postoperative hospital stay (P = 0.024). For 6-h cTnI, corresponding significance values were P = 0.29 and 0.9. ECG was of no value (P = 0.39 and 0.47). Differences in 24-h cTnI were highly significant, particularly for lowest vs highest tertiles, and allowed stratification of risk into "low" (<10 microg/L), "equivocal" (10-20 microg/L), and "high" (>20 microg/L). CONCLUSIONS: Use of a single 24-h cTnI value to quantify perioperative myocardial damage identifies patients who are at greater risk of extended ICU and hospital stays. This strategy could assist in allocation of patients to different management streams after CABG surgery.