Search

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. [ABSTRACT FROM AUTHOR]

For many years, the diagnosis of diabetes has been made through the laboratory-based measurement of fasting or random blood glucose levels, or using the oral glucose tolerance test. A glycated haemoglobin (HbA(1c)) level ≥ 6.5% (48 mmol/mol) is now also acceptable for diagnosing diabetes. Caution is needed in interpreting HbA(1c) test results in the presence of conditions affecting red blood cells or their survival time, such as haemoglobinopathies or anaemia. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are commonly ordered tests in general medical practice. However, their distribution and significance in older adults is understudied. As such, we aimed to evaluate sex-stratified distribution of both ALT and AST in older adults (≥ 70 years) and assess for associations with mortality., Methods: Post-hoc analysis of the ASPirin in Reducing Events in the Elderly (ASPREE) randomised, placebo-controlled trial of daily low-dose aspirin for initially relatively healthy older persons. Univariate analysis and multiple logistic regression were used to explore baseline characteristics. Cox regression and restricted cubic splines were used to examine links between transaminase levels and mortality., Results: Of the 11853 participants with ALT and AST levels, 1054 (8.9%) deaths were recorded over median 6.4 (IQR 5.4-7.6) years. For ALT, the lowest quintiles for males and females were 6-15 U/L and 5-13 U/L respectively; for AST, the lowest quintiles were 8-18 U/L and 7-17 U/L. On both univariate and models adjusted for covariates including age, BMI, frailty, diabetes, and kidney disease, males and females in the lowest quintile of ALT had an increased hazard of mortality (aHR 1.51 [95% CI 1.14-1.99] and aHR 1.39 [95% CI 1.03-1.88] respectively). For the lowest quintile of AST, only males were at increased risk (aHR 1.33 [95% CI 1.04-1.70]). Associations remained significant when removing outliers., Conclusion: Low ALT levels independently confer an increased hazard of mortality for older males and females; low AST only impacted older male survival. Further evaluation of mechanisms would be worthwhile, and re-evaluating the lower limit of normal for ALT in older adults should be considered., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Gerontological Society of America.)

Introduction: Critically ill patients are at risk of suboptimal beta-lactam antibiotic (beta-lactam) exposure due to the impact of altered physiology on pharmacokinetics. Suboptimal concentrations can lead to treatment failure or toxicity. Therapeutic drug monitoring (TDM) involves adjusting doses based on measured plasma concentrations and individualising dosing to improve the likelihood of improving exposure. Despite its potential benefits, its adoption has been slow, and data on implementation, dose adaptation and safety are sparse. The aim of this trial is to assess the feasibility and fidelity of implementing beta-lactam TDM-guided dosing in the intensive care unit setting., Methods and Analysis: A beta-lactam antibiotic Dose AdaPtation feasibility randomised controlled Trial using Therapeutic Drug Monitoring (ADAPT-TDM) is a single-centre, unblinded, feasibility randomised controlled trial aiming to enroll up to 60 critically ill adult participants (≥18 years). TDM and dose adjustment will be performed daily in the intervention group; the standard of care group will undergo plasma sampling, but no dose adjustment. The main outcomes include: (1) feasibility of recruitment, defined as the number of participants who are recruited from a pool of eligible participants, and (2) fidelity of TDM, defined as the degree to which TDM as a test is delivered as intended, from accurate sample collection, sample processing to result availability. Secondary outcomes include target attainment, uptake of TDM-guided dosing and incidence of neurotoxicity, hepatotoxicity and nephrotoxicity., Ethics and Dissemination: This study has been approved by the Alfred Hospital human research ethics committee, Office of Ethics and Research Governance (reference: Project No. 565/22; date of approval: 22/11/2022). Prospective consent will be obtained and the study will be conducted in accordance with the Declaration of Helsinki. The finalised manuscript, including aggregate data, will be submitted for publication in a peer reviewed journal. ADAPT-TDM will determine whether beta-lactam TDM-guided dose adaptation is reproducible and feasible and provide important information required to implement this intervention in a phase III trial., Trial Registration Number: Australian New Zealand Clinical Trials Registry, ACTRN12623000032651., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: A cardiovascular safety trial of testosterone in men with cardiovascular risk factors or disease found no difference in rates of major adverse cardiovascular events (MACE) or death but noted more atrial fibrillation (AF) events in testosterone-treated men. We investigated the relationship between endogenous testosterone concentrations with risk of developing AF in healthy older men., Methods: Post-hoc analysis of 4570 male participants in the ASPirin in Reducing Events in the Elderly (ASPREE) study. Men were aged ≥ 70 years, had no history of cardiovascular disease (including AF), thyroid disease, prostate cancer, dementia, or life-threatening illnesses. Risk of AF was modelled using Cox proportional hazards regression., Findings: Median (IQR) age was 73.7 (71.6-77.1) years and median (IQR) follow-up 4.4 (3.3-5.5) years, during which 286 men developed AF (15.3 per 1000 participant-years). Baseline testosterone was higher in men who developed incident AF compared men who did not [17.0 (12.4-21.2) vs 15.7 (12.2-20.0) nmol/L]. There was a non-linear association of baseline testosterone with incident AF. The risk for AF was higher in men with testosterone in quintiles (Q) 4&5 (Q4:Q3, HR = 1.91; 95%CI = 1.29-2.83 and Q5:Q3HR = 1.98; 95%CI = 1.33-2.94). Results were similar after excluding men who experienced MACE or heart failure during follow-up., Interpretation: Circulating testosterone concentrations within the high-normal range are independently associated with an increased risk of incident AF amongst healthy older men. This suggests that AF may be an adverse consequence of high-normal total testosterone concentrations., Funding: National Institute on Aging and National Cancer Institute at the National Institutes of Health; Australian Government (NHMRC, CSIRO); Monash University; and AlfredHealth., Competing Interests: Professor Yeap reported receiving research support funding from University of Western Australian, and an honoraria for presentations and participation in advisory committee, both of which are outside of the submitted work. Professor Schneider reported receiving a grant from Abbott Diagnostics for consumables and is an unpaid board member of Public Pathology Australia. Dr Woods reported receiving National Institute of Health (NIH) and National Health and Medical Research Council (NHMRC) funding, which is paid to Monash University., (© 2024 The Author(s).)

Background: The burden of metabolic dysfunction-associated steatotic liver disease (MASLD) is growing rapidly, including among older adults. The number of older adults is also rising with concomitantly increasing rates of age-related physical and cognitive dysfunction. However, data on whether MASLD affects physical and cognitive function in older adults is limited. As such, we aimed to identify whether prevalent MASLD influences the risk of incident physical disability or dementia in initially healthy older adults., Methods: A post-hoc analysis of participants from the ASPREE-XT cohort study, which recruited community-dwelling older adults without a history of cardiovascular disease, dementia, or independence-limiting functional impairment. The Fatty Liver Index (to identify MASLD) was calculated in those with complete data. Cox proportional-hazards models were used to investigate the outcomes of dementia and persistent physical disability in participants with MASLD vs those without., Results: Of the 9 097 individuals included (mean age 75.1 ± 4.2 years; 45.0% men), 341 (3.7%) developed persistent physical disability and 370 (4.1%) developed dementia over a median follow-up of 6.4 years (IQR 5.3-7.5 years). When adjusting for known contributors including age, gender, education, comorbidity, and functional measures, MASLD was associated with an increased risk of persistent physical disability (HR 1.41 [95% CI: 1.07-1.87]) and reduced risk of incident dementia (HR 0.63 [95% CI: 0.48-0.83])., Conclusions: Prevalent MASLD is associated with reduced rates of incident dementia but increased risk of persistent physical disability in initially relatively healthy older adults. Understanding the mechanisms underlying these divergent results to allow appropriate risk stratification and counseling is important., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Gerontological Society of America.)

Background: Aging increases fracture risk through bone loss and microarchitecture deterioration due to an age-related imbalance in bone resorption and formation during bone remodelling. We examined the associations between levels of phosphate, calcium, and alkaline phosphatase, and fracture risk in initially-healthy older individuals., Methods: A post-hoc analysis of the Aspirin in Reducing Events in the Elderly (ASPREE) trial recruited 16,703 Australian participants aged ≥70 years and 2,411 US participants aged ≥65 years. Analyses were conducted on ASPREE-Fracture substudy participants from Australia with serum calcium, phosphate, and alkaline phosphatase measurement. Fracture data were collected post-randomization. Cox regression was used to calculate hazard ratios (HR) and 95% confidence intervals (CIs). Phosphate, calcium, and alkaline phosphatase were analysed in deciles (D1-D10), with deciles 4-7 (31-70%) as the reference category. Restricted cubic spline curves were used to identify nonlinear associations., Results: Of the 9915 participants, 907 (9·2%) persons had incident fractures recorded over 3·9 (SD 1·4) years. In the fully adjusted model, males in the top decile (D10) of phosphate had 78% higher risk of incident fracture (HR 1·78, 95% CI 1·25-2·54). No such association was observed for females (HR 1·09, 95% CI 0·83-1·44). The population attributable fraction in men within the D10 phosphate category is 6·9%., Conclusion: This result confirms that, high-normal serum phosphate levels are associated with increased fracture risk in older men., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Objective: To measure the prevalence of alcohol and/or other drug (AOD) detections in suspected major trauma patients with non-transport injuries who presented to an adult major trauma centre., Methods: This registry-based cohort study examined the prevalence of AOD detections in patients aged ≥18 years who: (i) sustained non-transport injuries; and (ii) met predefined trauma call-out criteria and were therefore managed by an interdisciplinary trauma team between 1 July 2021 and 31 December 2022. Prevalence was measured using routine in-hospital blood alcohol and urine drug screens., Results: A total of 1469 cases met the inclusion criteria. Of cases with a valid blood test (n = 1248, 85.0%), alcohol was detected in 313 (25.1%) patients. Of the 733 (49.9%) cases with urine drug screen results, cannabinoids were most commonly detected (n = 103, 14.1%), followed by benzodiazepines (n = 98, 13.4%), amphetamine-type substances (n = 80, 10.9%), opioids (n = 28, 3.8%) and cocaine (n = 17, 2.3%). Alcohol and/or at least one other drug was detected in 37.4% (n = 472) of cases with either a blood alcohol or urine drug test completed (n = 1263, 86.0%). Multiple substances were detected in 16.6% (n = 119) of cases with both blood alcohol and urine drug screens (n = 718, 48.9%). Detections were prevalent in cases of interpersonal violence (n = 123/179, 68.7%) and intentional self-harm (n = 50/106, 47.2%), and in those occurring on Friday and Saturday nights (n = 118/191, 61.8%)., Conclusion: AOD detections were common in trauma patients with non-transport injury causes. Population-level surveillance is needed to inform prevention strategies that address AOD use as a significant risk factor for serious injury., (© 2023 The Authors. Emergency Medicine Australasia published by John Wiley & Sons Australia, Ltd on behalf of Australasian College for Emergency Medicine.)

Objective: To formulate clinical consensus recommendations on the presentation, assessment, and management of primary hyperparathyroidism (PHPT) in adults., Methods: Representatives from relevant Australian and New Zealand Societies used a systematic approach for adaptation of guidelines (ADAPTE) to derive an evidence-informed position statement addressing nine key questions., Results: PHPT is a biochemical diagnosis. Serum calcium should be measured in patients with suggestive symptoms, reduced bone mineral density or minimal trauma fractures, and in those with renal stones. Other indications are detailed in the manuscript. In patients with hypercalcaemia, intact parathyroid hormone, 25-hydroxy vitamin D, phosphate, and renal function should be measured. In established PHPT, assessment of bone mineral density, vertebral fractures, urinary tract calculi/nephrocalcinosis and quantification of urinary calcium excretion is warranted. Parathyroidectomy is the only definitive treatment and is warranted for all symptomatic patients and should be considered for asymptomatic patients without contraindications to surgery and with >10 years life expectancy. In patients who do not undergo surgery, we recommend annual evaluation for disease progression. Where the diagnosis is not clear or the risk-benefit ratio is not obvious, multidisciplinary discussion and formulation of a consensus management plan is appropriate. Genetic testing for familial hyperparathyroidism is recommended in selected patients., Conclusions: These clinical consensus recommendations were developed to provide clinicians with contemporary guidance on the assessment and management of PHPT in adults. It is anticipated that improved health outcomes for individuals and the population will be achieved at a decreased cost to the community., (© 2021 John Wiley & Sons Ltd.)

Background & Aims: The burden of metabolic dysfunction-associated steatotic liver disease (MASLD) is growing rapidly, as is the number of older adults globally. However, relatively few studies have been performed evaluating the prevalence and risk factors for MASLD in older adults. As such, we aimed to identify the prevalence of MASLD in older adults, as well as sociodemographic, clinical, functional and biochemical associations., Methods: The study population included older adults without a history of cardiovascular disease, dementia or independence-limiting functional impairment who had participated in the ASPirin in Reducing Events in the Elderly (ASPREE) randomised trial. MASLD was defined using the Fatty Liver Index (FLI). Associations were identified using Poisson regression with robust variance for FLI ≥ 60 vs FLI < 30., Results: 9097 Australian participants aged ≥70 years had complete biochemical and anthropometric data to identify MASLD. The study population had a mean age of 75.1 ± 4.3 years and was 45.0% male. Almost one-third (33.0%) had prevalent MASLD, and the prevalence decreased with increasing age (adjusted RR [aRR] 0.96, 95% CI: 0.96-0.97). MASLD was also negatively associated with social advantage (aRR 0.94, 95% CI: 0.90-0.99) and exercise tolerance and was positively associated with diabetes mellitus (aRR: 1.22, 95% CI: 1.16-1.29), hypertension (aRR: 1.31, 95% CI: 1.22-1.41), male sex (aRR: 1.66, 95% CI: 1.57-1.74), pre-frailty (aRR: 1.99, 95% CI: 1.82-2.12) and frailty (aRR: 2.36, 95% CI: 2.16-2.56). MASLD and nonalcoholic fatty liver disease (NAFLD) results were 100% concordant., Conclusion: This study in a large cohort of relatively healthy community-dwelling older adults shows that MASLD is common, decreases with age and is associated with poorer metabolic health, social disadvantage and frailty., (© 2023 The Authors. Liver International published by John Wiley & Sons Ltd.)

Background: Daily low-dose aspirin increases major bleeding; however, few studies have investigated its effect on iron deficiency and anemia., Objective: To investigate the effect of low-dose aspirin on incident anemia, hemoglobin, and serum ferritin concentrations., Design: Post hoc analysis of the ASPREE (ASPirin in Reducing Events in the Elderly) randomized controlled trial. (ClinicalTrials.gov: NCT01038583)., Setting: Primary/community care in Australia and the United States., Participants: Community-dwelling persons aged 70 years or older (≥65 years for Black persons and Hispanic persons)., Intervention: 100 mg of aspirin daily or placebo., Measurements: Hemoglobin concentration was measured annually in all participants. Ferritin was measured at baseline and 3 years after random assignment in a large subset., Results: 19 114 persons were randomly assigned. Anemia incidence in the aspirin and placebo groups was 51.2 events and 42.9 events per 1000 person-years, respectively (hazard ratio, 1.20 [95% CI, 1.12 to 1.29]). Hemoglobin concentrations declined by 3.6 g/L per 5 years in the placebo group and the aspirin group experienced a steeper decline by 0.6 g/L per 5 years (CI, 0.3 to 1.0 g/L). In 7139 participants with ferritin measures at baseline and year 3, the aspirin group had greater prevalence than placebo of ferritin levels less than 45 µg/L at year 3 (465 [13%] vs. 350 [9.8%]) and greater overall decline in ferritin by 11.5% (CI, 9.3% to 13.7%) compared with placebo. A sensitivity analysis quantifying the effect of aspirin in the absence of major bleeding produced similar results., Limitations: Hemoglobin was measured annually. No data were available on causes of anemia., Conclusion: Low-dose aspirin increased incident anemia and decline in ferritin in otherwise healthy older adults, independent of major bleeding. Periodic monitoring of hemoglobin should be considered in older persons on aspirin., Primary Funding Source: National Institutes of Health and Australian National Health and Medical Research Council., Competing Interests: Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M23-0675.

Immunoassays are routinely used to provide rapid urine drug screening results in the clinical setting. These screening tests are prone to false-positive results and ideally require confirmation by mass spectrometry. In this study, we have examined a large number of urine specimens where drugs other than amphetamines may have caused a false-positive amphetamine immunoassay screening result. Urine drug screens (12,250) in a clinical laboratory that used the CEDIA amphetamine/ecstasy method were reviewed for false-positive results over a 6-year period (2015-2020). An additional 3,486 referred samples, for which confirmatory--mass spectrometry was requested, were also reviewed. About 86 in-house samples and 175 referral samples that were CEDIA false-positive screens were further analyzed by an LC-QTOF general unknown screen. Potential cross-reacting drugs were identified, and their molecular similarities to the CEDIA targets were determined. Commercial standards were also analyzed for cross-reactivity in the amphetamine/ecstasy CEDIA screen. Positive amphetamine results in 3.9% of in-house samples and 9.9% of referred tests for confirmatory analysis were false positive for amphetamines. Of these false-positive specimens, on average, 6.8 drugs were detected by the LC-QTOF screen. Several drugs were identified as possible cross-reacting drugs to the CEDIA amphetamine/ecstasy assay. Maximum common substructure scores for 70 potential cross-reacting compounds were calculated. This was not helpful in identifying cross-reacting drugs. False-positive amphetamine screens make up to 3.9-9.9% of positive amphetamine screens in the clinical laboratory. Knowledge of cross-reacting drugs may be helpful when mass spectrometry testing is unavailable., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Low serum alkaline phosphatase (ALP) was found in 9% of patients attending an osteoporosis clinic, 0.6% of hospital patients, and 2/22 with an atypical femoral fracture. Hypophosphatasia was diagnosed in 3% of osteoporosis clinic patients with low ALP. Low ALP is a screening tool for hypophosphatasia, a condition potentially aggravated by antiresorptive therapy., Introduction: Hypophosphatasia (HPP) is an inherited disorder associated with impaired primary mineralisation of osteoid (osteomalacia). HPP may be misdiagnosed as osteoporosis, a reduction in the volume of normally mineralized bone. Both illnesses may result in fragility fractures, although stress and atypical fractures are more common in HPP. Antiresorptive therapy, first-line treatment for osteoporosis, is relatively contraindicated in HPP. Misdiagnosis and mistreatment can be avoided by recognising a low serum alkaline phosphatase (ALP). Our aim was to determine the prevalence of a low ALP (< 30 IU/L) in patients attending an osteoporosis clinic, in a hospital-wide setting, and in a group of patients with atypical femoral fractures (AFF)., Methods: This was a retrospective study of patients attending an osteoporosis clinic at a tertiary hospital during 8 years (2012-2020). Patients were categorised into those with a transiently low ALP, those with low ALP on ≥ 2 occasions but not the majority of measurements, and those with a persistently low ALP. ALP levels were also assessed in hospital-wide records and a group of patients with AFF., Results: Of 1839 patients attending an osteoporosis clinic, 168 (9%) had ≥ 1 low ALP, 50 (2.7%) had low ALP for ≥ 2 months, and seven (0.4%) had persistently low ALP levels. HPP was diagnosed in five patients, four of whom had persistently low ALP levels. The prevalence of HPP was 0.3% in the osteoporosis clinic and 3% in patients with ≥ 1 low ALP. Low ALP occurred in 0.6% of all hospital patients and 2/22 with AFF., Conclusion: Persistently low ALP in osteoporosis clinic attendees is easy to identify and signals the possibility of hypophosphatasia, a condition that may be mistaken for osteoporosis and incorrectly treated with antiresorptive therapy., (© 2022. Crown.)

Objective: To develop evidence-based recommendations to guide the surgical management and postoperative follow-up of adults with primary hyperparathyroidism., Methods: Representatives from relevant Australian and New Zealand Societies used a systematic approach for adaptation of guidelines (ADAPTE) to derive an evidence-informed position statement addressing eight key questions., Results: Diagnostic imaging does not determine suitability for surgery but can guide the planning of surgery in suitable candidates. First-line imaging includes ultrasound and either parathyroid 4DCT or scintigraphy, depending on local availability and expertise. Minimally invasive parathyroidectomy is appropriate in most patients with concordant imaging. Bilateral neck exploration should be considered in those with discordant/negative imaging findings, multi-gland disease and genetic/familial risk factors. Parathyroid surgery, especially re-operative surgery, has better outcomes in the hands of higher volume surgeons. Neuromonitoring is generally not required for initial surgery but should be considered for re-operative surgery. Following parathyroidectomy, calcium and parathyroid hormone levels should be re-checked in the first 24 h and repeated early if there are risk factors for hypocalcaemia. Eucalcaemia at 6 months is consistent with surgical cure; parathyroid hormone levels do not need to be re-checked in the absence of other clinical indications. Longer-term surveillance of skeletal health is recommended., Conclusions: This position statement provides up-to-date guidance on evidence-based best practice surgical and postoperative management of adults with primary hyperparathyroidism., (© 2021 John Wiley & Sons Ltd.)

Objective: Validation of a non-targeted method for urine drug screening (UDS) by liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF), and comparison to an established GC-MS method in a hospital setting., Methods: 217 UDS specimens sent to a quaternary hospital pathology department, were analysed by a CEDIA® immunoassay screen (six drug panels; amphetamines, barbiturates, benzodiazepines, cocaine metabolites, cannabinoids and opiates) on an Abbott Architect instrument. Specimens were subsequently analysed by an established non-targeted qualitative GC-MS method and results compared with a general unknown screening method by LC-QTOF that was under evaluation as a replacement method., Results: 42 selected drugs were evaluated; limits of identification ranged from 2 to 100 µg/L and most drugs (n = 39) were stabile for 24 h after preparation. Matrix effects greater than 25% were observed in seven of the selected drugs. 87% of the specimens tested positive to 1 or more drug panels in a CEDIA® screen. A total of 537 positive drug findings were identified by GC-MS compared to 1,267 positive findings by LC-QTOF. On average, each GC-MS screen identified 2.5 ± 1.8 drugs and the LC-QTOF screen identified 5.8 ± 3.2 drugs. No drugs were identified in 11.3% of the GC-MS screens, whereas drugs were detected in 99% of these by the LC-QTOF. In almost all instances, the LC-QTOF screen could provide mass spectrometric confirmatory results of positive immunoassay screens and was able to identify a wider range of additional drugs and drug metabolites., Conclusions: The described general unknown screening (non-targeted, qualitative) LC-QTOF method can detect a larger range of drugs encountered in a hospital setting. The method has been shown to be suitable for comprehensive toxicology screening in a clinical toxicology laboratory., (Copyright © 2021 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Background: Albumin-adjusted calcium remains widely used in clinical practice with guidelines for chronic kidney disease (CKD) mineral bone disorder recommending the use of serum calcium for monitoring. This is despite ionized calcium being the biologically active fraction. This study aimed to investigate the ability of total calcium and albumin-adjusted calcium to correctly assign calcium status in stage 5/5D CKD across non-dialysis, haemodialysis and peritoneal dialysis patients., Methods: Over a 6-months, 352 paired serum and ionized calcium samples were collected from stage 5 (n = 58) and 5D (n = 294, 196 haemodialysis, 98 peritoneal dialysis) CKD patients in a tertiary-hospital setting. Albumin-adjusted calcium was calculated using the modified-Payne formula. Ionized calcium was the reference standard. The agreement between the two methods in assigning calcium status was assessed using Cohen's weighted kappa (κ) statistic., Results: Albumin-adjusted calcium was a poor predictor of calcium status compared to ionized calcium in stage 5/5D CKD (observed agreement 0.42, weighted κ 0.20, 95% CI 0.15-0.26). Dialysis dependence was associated with worse agreement (observed agreement 0.38, weighted κ 0.14, 95% CI 0.09-0.19). Total calcium was more reliable, however, remained inaccurate. Calcium status was not more accurately classified in those with higher albumin levels ≥30 g/L (observed agreement 0.47, weighted κ 0.23, 95% CI 0.10-0.36)., Conclusion: Total calcium provides better approximation of calcium status than albumin-adjusted calcium in stage 5/5D CKD. Albumin-adjusted calcium tends to 'overcorrect' serum calcium upward. Clinicians should use ionized calcium where accurate measure of calcium is indicated, with total calcium used as the next best option where resources are limited., (© 2021 Asian Pacific Society of Nephrology.)

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., (© 2021 Royal Australasian College of Physicians.)

Competing Interests: Competing Interests: None declared.

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., (© 2019 Royal Australasian College of Physicians.)

Background: In critically ill patients, who require multiple blood gas assessments, agreement between arterial and venous blood gas values for pH and partial pressure of carbon dioxide, is not clear. Good agreement would mean that venous values could be used to assess ventilation and metabolic status of patients in intensive care unit., Methods: All adult patients admitted to Alfred intensive care unit, Melbourne, from February 2013 to January 2014, who were likely to have arterial and central venous lines for three days, were enrolled. Patients on extra-corporeal life support and pregnant women were excluded. After enrolment, near simultaneous arterial and central venous sampling and analysis were performed at least once per nursing shift till the lines were removed or the patient died. Bland-Altman analysis for repeated measures was performed to assess the agreement between arterio-venous pH and partial pressure of carbon dioxide., Results: A total of 394 paired blood gas analyses were performed from 59 participants. The median (IQR) number of samples per patient was 6 (5-9) with the median (IQR) sampling interval 9.4 (5.2-18.5) h. The mean bias for pH was  + 0.036 with 95% limits of agreement ranging from - 0.005 to + 0.078. For partial pressure of carbon dioxide, the values were -2.58 and -10.43 to + 5.27 mmHg, respectively., Conclusions: The arterio-venous agreement for pH in intensive care unit patients appears to be acceptable. However, the agreement for partial pressure of carbon dioxide was poor., (© The Intensive Care Society 2019.)

Objective: The cause of perioperative myocardial infarction (PMI) is postulated to involve hemodynamic stress or coronary plaque destabilization. We aimed to evaluate perioperative factors in patients with peripheral artery disease (PAD) undergoing major vascular surgery to determine the likely mechanisms and predictors of PMI., Methods: This was a prospective cohort study of 133 patients undergoing major vascular surgery including open abdominal aortic aneurysm (AAA) repair (n = 40) and major suprainguinal or infrainguinal arterial bypasses (non-AAA; n = 93). Preoperative assessment with history, physical examination, and peripheral artery tonometry was performed in addition to plasma sampling of biomarkers associated with inflammation and coronary plaque instability. The primary outcome was occurrence of a 30-day cardiovascular event (CVE; composite of PMI [troponin I elevation >99th percentile reference of ≥0.1 μg/L], stroke, or death)., Results: Of 133 patients, 36 patients (27%) developed a 30-day CVE after vascular surgery, and all were PMI. Patients with 30-day CVE were older (75 ± 8 years vs 69 ± 10 years, mean ± standard deviation; P = .001), had higher prevalence of hypertension (94% vs 79%; P = .01) and preoperative beta-blocker therapy (50% vs 29%; P = .02), and had longer duration of surgery (5.1 ± 1.8 hours vs 4.0 ± 1.1 hours; P < .0001). Significant elevations in cystatin C, N-terminal pro-B-type natriuretic peptide (NT-proBNP), troponin I, high-sensitivity troponin T, matrix metalloproteinase 3, and osteoprotegerin occurred in those who developed 30-day CVE (all P < .05). Multivariate binary logistic regression identified AAA surgery and log-transformed NT-proBNP to be independent preoperative predictors of 30-day CVE (area under the receiver operating characteristic curve = 0.81)., Conclusions: In patients with peripheral artery disease undergoing major vascular surgery, the likely mechanism of PMI appears to be the hemodynamic stress related to the type and duration of surgery. NT-proBNP was a useful independent predictor of CVE and thus may serve as an important biomarker of cardiovascular fitness for surgery., (Copyright © 2019 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Ayahausca is an ethnobotanical drink of South America and the compound dimethyltryptamine (DMT) is primarily responsible for the hallucinogenic effects. DMT has a short half-life and its detection in urinary drug screens is challenging. We investigate a simple alternate approach to detect ayahuasca consumption by relying on other constituents of the drink, the β-carboline harmala alkaloids., Methods: Three commercially sourced harmala alkaloids were characterized and added to a non-targeted high-resolution mass spectrometry urine drug screening method. All analyses were performed on a Waters Xevo G2-XS LC-QTof, in positive electrospray ionization mode. The mass detector was operated in MSE mode and data processed with UNIFI™ software. A urine specimen from a patient suspected to have consumed ayahuasca was analyzed by a non-targeted drug screen., Results: The harmala alkaloids: harmine, harmaline and tetrohydroharmaline (THH) were characterized and their detection data added to the toxicology screening library. Harmaline and THH were detected in the patient's urine specimen., Conclusion: The inclusion of the harmala alkaloids into the drug screen method library may enable the detection of ayahuasca use in patients that undergo non-targeted drug screen., (© The Author(s) 2018. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Clinical laboratories measure total calcium and adjust for albumin concentrations to predict calcium status. We compared total and adjusted calcium (Adj-Ca) with ionized calcium (Ca 2+ ) for correct assignment of calcium status. The effect of restriction of Adj-Ca reporting in patients with hypoalbuminemia was determined on the basis of frequency of misclassifications., Methods: Extraction of laboratory results was performed for 24 months. Adj-Ca was calculated from a modified Payne formula. A further prospective data set for 6 months was collected after stopping reporting of Adj-Ca for patients with an albumin <3.0 g/dL. The agreement between Ca 2+ and Adj-Ca or total Ca was assessed with Cohen's kappa statistic., Results: In 5553 hospitalized patients, 13604 paired Ca 2+ results were analyzed retrospectively. Prospective collection in 1113 paired samples was from 450 patients. Adj-Ca was a poor predictor of calcium status compared to the Ca 2+ reference standard in both data sets (agreement 56.9% in the first, 65.6% in the second data set). Renal failure and low albumin concentrations were associated with worse agreement between Adj-Ca and Ca 2+ . Restriction of reporting of Adj-Ca to albumin concentrations >3.0g/dL improved correct classification of calcium status from 65.6% to 77.6% ( P < 0.0001). Total Ca performed better than Adj-Ca for low albumin (<3.0g/dL) and performed similarly in samples with albumin >3.0g/dL., Conclusions: Adj-Ca is unreliable for the classification of calcium status in hospital patients when compared to Ca 2+ . Adj-Ca overestimates calcium for patients with renal impairment and albumin concentrations <3.0g/dL. Restriction of reporting Adj-Ca for albumin below 3.0 g/dL reduces the number of misclassified patients., (© 2018 American Association for Clinical Chemistry.)

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.

Cocaine use in Australia is increasing, with approximately 2.5% of the surveyed population having used cocaine. In the USA, levamisole, a widely used anti-helminthic veterinary drug has been increasingly detected as a cutting agent in cocaine seizures. Levamisole is known to cause agranulocytosis in humans. We ascertained the prevalence of levamisole-adulterated cocaine, detectable in the urine from patients that had undergone a pathology request for a urine drug screen. We assayed routinely requested urines that were positive for cocaine on immunoassay with liquid chromatography high resolution quadrupole time of flight mass spectrometry (LC-QToF). We investigated available urine samples from a period of 2 years that had a positive result for cocaine. In addition, we examined samples that were below the cut-off for cocaine on immunoassay. Specimens were analysed for the presence of levamisole and other 'unknown' drugs. In the period under investigation the laboratory examined 3665 urine samples for cocaine: 1.4% (n = 51) of the samples were positive for cocaine by immunoassay and half of these (n = 26, 51%) were further examined by LC-QToF. In addition, we examined 10 samples that were negative by immunoassay (as defined by AS/NZS 4308:2008). Levamisole was detected in the urine of cocaine users in approximately 75% of cases. Other illicit drugs were also frequently found in this cohort. The most common illicit drugs detected were methamphetamine, ecstasy and cannabis. Australian cocaine is widely adulterated with levamisole. Cocaine users are at risk of levamisole related health problems in addition to the problems related to cocaine., (Copyright © 2018 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.)

Objective: To determine variables that could facilitate safe discharge from the ED following a single high-sensitivity troponin I (HsTnI) result to exclude acute myocardial infarction (AMI)., Methods: A retrospective cohort study was performed at a tertiary hospital of all patients that had serial HsTnI performed within 12 h of arrival to the ED over a 3 year period. The primary exposure variable of interest was a very low troponin initial result (HsTnI <5 ng/L). Medical record review and risk stratification score calculations were undertaken for all patients with the exposure variable of interest and an abnormal second troponin measurement (HsTnI ≥16 ng/L in women and HsTnI ≥26 ng/L in men)., Results: There were 11 970 patients who presented between 1 July 2013 and 30 June 2016 that had serial HsTnI measurements performed. Of these, 4172 (34.9%) patients had an initial HsTnI measurement <5 ng/L. Of the patients with an initial HsTnI <5 ng/L that met inclusion criteria, 56 (1.3%) had a second troponin result above the 99th percentile and 32 (0.8%) cases of non-ST elevation myocardial infarction were diagnosed as well as 15 (0.4%) cases of ST elevation myocardial infarction. There were 44 (93.6%) of all AMI cases that met criteria for high-risk presentations under the National Heart Foundation of Australia guidelines. The negative predictive value of an initial HsTnI <5 ng/L to exclude AMI was 98.9% (95% confidence interval 98.5-99.1)., Conclusions: This supports the utilisation of a rapid rule out strategy to exclude AMI for patients that have an initial HsTnI measurement <5 ng/L in conjunction with a robust risk assessment., (© 2017 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine.)

Objectives: To identify the contents of pills found on an intoxicated patient by ultrahigh-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC-QTof).5 To highlight the potential ability that this technique can add to the clinical laboratory., Methods: Illicit PEZ-like pills purchased from an online vendor, containing unknown substances, were investigated by UHPLC-QTof. Accurate mass and experimental data were obtained. Tentative identifications were subsequently confirmed with commercial standards., Results: Accurate mass data, high-energy mass spectra, elucidation software, and a review of the scientific literature enabled the tentative identification of clonazolam and flubromazolam in the PEZ-like pills. On the basis of these tentative identifications, commercial standards were purchased to confirm the initial findings. On subsequent reinterrogation of the data, flubromazolam was identified in the urine specimen of the patient., Conclusions: Utilizing high-resolution mass data, 2 novel benzodiazepines were tentatively identified by reinterrogation of a routine analysis for drugs of abuse. Use of UHPLC-QTof in a clinical toxicology laboratory provides additional capabilities to explain and potentially improve treatment of patients presenting to the emergency department with symptoms possibly due to toxic substance ingestion., (© 2018 American Association for Clinical Chemistry.)

Introduction: Invasive fungal infections are an increasing cause of mortality and morbidity in high risk patient populations such as those on immunosuppressive therapy. Triazole antifungals are recommended for the prevention and treatment of such infections. The aim of this study was to develop and validate a simple, sensitive and robust LCMS/MS method for the simultaneous analysis in human plasma of three frequently used antifungal drugs: voriconazole, posaconazole, and itraconazole., Methods: Precipitation reagent, containing deuterated internal standards, is added to 50μL of plasma. The vials are vortexed before centrifugation. The organic supernatant is transferred to a polypropylene vial and 1μL is injected into the Waters Acquity® Ultra Performance Liquid Chromatography system coupled with a Waters Acquity® TQ Detector system. Chromatographic separation is achieved on a BEH C 18 column using gradient elution with mobile phases consisting of 2mM ammonium acetate with 0.1% formic acid in water and methanol. Run time is <5min between injections., Results: The evaluation of the LCMS/MS triazole method showed good precision (intra-assay CVs<6.7%, inter-assay CVs<8.3%). The lower limit of quantitation for all antifungal triazoles tested was 0.10mg/L. Passing Bablok comparisons of voriconazole (n=50) and posaconazole (n=50) showed good correlation with the current HPLC method (Voriconazole LCMS=0.94(HPLC)+0.03, r 2 =0.99; Posaconazole LCMS=1.18(HPLC)-0.04, r 2 =0.95). Passing Bablok comparisons of itraconazole and hydroxy-itraconazole (n=18) showed good agreement with an external referral laboratory's antifungal LCMS/MS method (Itraconazole LCMS=1.00(referral lab)+0.01, r 2 =0.99; Hydroxy-Itraconazole LCMS=1.05(referral lab)+0.04, r 2 =0.99). External quality assurance samples for posaconazole and voriconazole (n=12, UK NEQAS Antifungal Pilot Panel) were assayed 'blind' and results were in good agreement with consensus mean values (both r 2 =0.99)., Conclusion: The rapid pre-analytical sample preparation procedure, short chromatographic time, limit of quantitation and linear range make this LCMS/MS method suitable for determination of plasma voriconazole, posaconazole, itraconazole and hydroxy-itraconazole levels in a high throughput laboratory., (Copyright © 2018 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

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.

Background: Valproic acid (VPA) is a widely prescribed medicine, and acute toxicity is possible. As such, it should be included in any nontargeted urine drug screening method. In many published liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS/MS) methods, VPA is usually measured using a pseudo-multiple reaction monitoring (MRM) transition. We investigate a simple ultra-high-performance liquid chromatography-quadrupole time-of-flight (QTof) approach to detect the presence of VPA with more confidence., Methods: Three commercially sourced VPA metabolites were characterized and added to a nontargeted high-resolution MS urine drug screening method. All analyses were performed on a Waters Xevo G2-XS LC-QTof in negative electrospray ionization mode. The mass detector was operated in MS mode, and data were processed with UNIFI software. Sixty-eight patient urine samples, which were previously identified by a well-established gas chromatography-MS method as containing VPA, were analyzed on the Waters Xevo G2-XS LC-QTof, to validate this approach., Results: VPA metabolite standards were characterized, and their detection data were added to the broad drug screening library. VPA metabolites were readily detectable in the urine of patients taking VPA., Conclusions: The inclusion of characterized VPA metabolites provides a simple and reliable method enabling the detection of VPA in nontargeted urine drug screening.

Atherosclerosis is a major cause of mortality and morbidity, which is mainly driven by complications such as myocardial infarction and stroke. These complications are caused by thrombotic arterial occlusion localized at the site of high-risk atherosclerotic plaques, of which early detection and therapeutic stabilization are urgently needed. Here we show that near-infrared autofluorescence is associated with the presence of intraplaque hemorrhage and heme degradation products, particularly bilirubin by using our recently created mouse model, which uniquely reflects plaque instability as seen in humans, and human carotid endarterectomy samples. Fluorescence emission computed tomography detecting near-infrared autofluorescence allows in vivo monitoring of intraplaque hemorrhage, establishing a preclinical technology to assess and monitor plaque instability and thereby test potential plaque-stabilizing drugs. We suggest that near-infrared autofluorescence imaging is a novel technology that allows identification of atherosclerotic plaques with intraplaque hemorrhage and ultimately holds promise for detection of high-risk plaques in patients.Atherosclerosis diagnosis relies primarily on imaging and early detection of high-risk atherosclerotic plaques is important for risk stratification of patients and stabilization therapies. Here Htun et al. demonstrate that vulnerable atherosclerotic plaques generate near-infrared autofluorescence that can be detected via emission computed tomography.

Background: There has been limited examination of the performance of glomerular filtration rate estimation (eGFR) equations in lung transplant populations. This study aimed to compare the performance of serum creatinine and cystatin C based eGFR equations with Tc-99m diethylenetriaminepentaacetic acid (DTPA) GFR measurements in individuals with end-stage lung disease, either prior to, or following, lung transplantation., Methods: In this prospective observational study, participants underwent GFR measurements with Tc-99m Pentetate. Measured results were compared with GFR estimates derived from estimation equations [4-variable Modification of Diet in Renal Disease, Cockcroft-Gault, Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine, cystatin C and creatinine-cystatin C combined equations]., Results: Ninety-seven individuals were studied (77 post- and 20 wait-listed for transplantation). Median (range) radionucleotide GFR was 56.7ml/min/1.73m 2 (22.8-109.2ml/min/1.73m 2 ). In the study cohort as a whole, the CKD-EPI creatinine-cystatin C combined equation showed the highest performance, but was only slightly superior to the CKD-EPI creatinine equation. However, in individuals with cystic fibrosis, low arm muscle mass and/or low body mass index, all of the creatinine-based equations showed unacceptable performance. In these subgroups, improved GFR estimation was seen with the CKD-EPI cystatin C equation, and predictions were better still using the CKD-EPI creatinine-cystatin C combined equation., Conclusions: This study shows adequate predictive ability of CKD-EPI creatinine in the cohort as a whole, but unacceptable performance in patients with cystic fibrosis, low arm muscle mass and/or low body mass index. Our findings demonstrate that cystatin C may be a preferable filtration marker in these subgroups., (Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Background: Macrophage migration inhibitory factor (MIF) is a key regulator of inflammatory responses, including in the heart. Plasma MIF is elevated early in the course of acute myocardial infarction. In this study, we hypothesized that plasma MIF may also be increased in acute myocardial ischemia., Methods and Results: Patients undergoing cardiac stress test (stress nuclear myocardial perfusion scan or stress echocardiography) were recruited. Twenty-two patients had a stress test indicative of myocardial ischemia and were compared with 62 patients who had a negative stress test. Plasma MIF was measured by ELISA before and after the stress test. MIF was also measured in patients with peripheral arterial occlusive disease before and after exercise causing claudication. Gene and protein expression of MIF was measured in mouse cardiac and skeletal muscle tissue by real-time polymerase chain reaction and western blot, respectively. Plasma MIF was elevated at 5 and 15 minutes after stress (relative to before stress) in patients with a positive test, compared with those with a negative test. In contrast, high-sensitivity troponin T and C-reactive protein were not altered after stress in either group. MIF was not altered after exercise in PAOD patients, despite the occurrence of claudication, suggesting that plasma MIF is not a marker for skeletal muscle ischemia. This may be explained by a lower gene and protein expression of MIF in skeletal muscle than the heart., Conclusions: Our results suggest that plasma MIF is an early marker for acute myocardial ischemia., (© 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Monoclonal gammopathies are characterised by the production of a monoclonal immunoglobulin or free light chains by an abnormal plasma cell or B-cell clone and may indicate malignancy or a precursor (MGUS). There is currently no consensus on the initial test or combination of tests to be performed in suspected monoclonal gammopathies but serum protein electrophoresis and urine protein electrophoresis are commonly requested as initial investigations. If abnormal, immunofixation electrophoresis is then performed to confirm the presence of paraprotein and to determine its heavy and light chain type. Recently, some groups have developed simplified "screening" IFE methods for use in parallel to SPEP for the detection monoclonal gammopathies. We argue here that screening IFE may be of benefit in clinical laboratories using SPEP with poor resolution in the β-region, assisting in the detection of mainly IgA paraprotein, but may be of less benefit in laboratories utilising higher resolution gels. Further it may increase the detection of trace bands of questionable clinical significance, representing transient phenomena in infectious and auto-immune conditions or very low risk MGUS. The increased detection of these bands using screening IFE would require further patient follow up, possibly causing unnecessary patient anxiety and additional follow up healthcare costs.

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., (© 2016 American Association for Clinical Chemistry.)

Unlabelled: Background In some studies HIV infection confers approximately two-fold higher risk of cardiac events compared with the general population. C-reactive protein (CRP) is a well-characterised biomarker of cardiac events in the general population and is also elevated in patients with HIV infection. The aim of this study was to determine the predictive value of CRP for cardiac events in HIV-infected individuals., Methods: We retrospectively analysed CRP levels in stored plasma samples from HIV-infected patients who did or did not experience a coronary event in a case-controlled manner. All CRP measurements were performed using a high-sensitivity assay (hs-CRP)., Results: Of the study participants with samples available, we found slightly elevated hs-CRP levels in the cardiac cases (median 3.5, IQR 1.6-14.4, n=23) compared with controls (median 2.6, IQR1.2-8.3, n=49) which were shown to not be statistically significant P=0.20. Analysis of CRP as a binary variable (≥5mgL(-1)) was also not statistically significant (OR: 1.32, 95% CI 0.48-3.63)., Conclusions: CRP levels may indicate elevated risk of future cardiac events, however this must be interpreted with caution due to the generalised elevation of CRP during HIV infection. CRP has no predictive value for atherosclerosis, and further research is required to improve early prediction of cardiovascular disease in HIV infection.

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 β-isomerised carboxy-terminal cross-linking telopeptide of type I collagen (s-CTX).

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-βCTX) 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-βCTX.