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Introduction Mycophenolate sodium, an enteric-coated tablet (EC-MPS), is as effective and safe as mycophenolate mofetil (MMF) in preventing transplant rejection. EC-MPS and MMF improve the outcome of severe lupus nephritis (LN) and have fewer side effects than pulsed intravenous cyclophosphamide. Blood concentrations of mycophenolic acid (MPA), the active metabolite of EC-MPS, vary between participants despite fixed dosing. Interpatient variability has been studied in transplantation, but not well documented in LN. The relationship between MPA concentration and its clinical effect on LN has not been described. Methods and analysis This is a prospective, open-label, randomised controlled trial. –32 participants with LN who meet the inclusion and exclusion criteria will be randomised into two groups: one receiving a fixed dose of EC-MPS and the second, a dosing regimen that is titrated with therapeutic drug monitoring. Included participants will have blood sampled over a period of 8–12 h on three different occasions. Pharmacokinetic parameters will be calculated using non-compartmental methods. Ethics and dissemination The Human Research and Ethics Committee of the Royal Brisbane Women9s Hospital have approved this study. The study is registered with Australian and New Zealand Clinical Trials Registry—ACTRN12611000798965 We planned to present the de-identified information at conferences and publish the results in medical journals. Trial Registration ACTRN12611000798965

Objectives The study objective was to validate a new high-sensitivity troponin I (hs-TnI) assay in a clinical protocol for assessing patients who present to the emergency department with chest pain. Background Protocols using sensitive troponin assays can accelerate the rule out of acute myocardial infarction in patients with low-risk (suspected) acute coronary syndrome (ACS). Methods This study evaluated 2 prospective cohorts of patients in the emergency department with ACS in an accelerated diagnostic pathway integrating 0- and 2-h hs-TnI results, Thrombolysis In Myocardial Infarction (TIMI) risk scores, and electrocardiography. Strategies to identify low-risk patients incorporated TIMI risk scores = 0 or ≤1. The primary endpoint was a major adverse cardiac event (MACE) within 30 days. Results In the primary cohort, 1,635 patients were recruited and had 30-day follow-up. A total of 247 patients (15.1%) had a MACE. The finding of no ischemic electrocardiogram and hs-TnI ≤26.2 ng/l with the TIMI = 0 and TIMI ≤1 pathways, respectively, classified 19.6% (n = 320) and 41.5% (n = 678) of these patients as low risk; 0% (n = 0) and 0.8% (n = 2) had a MACE, respectively. In the secondary cohort, 909 patients were recruited. A total of 156 patients (17.2%) had a MACE. The TIMI = 0 and TIMI ≤1 pathways classified 25.3% (n = 230) and 38.6% (n = 351), respectively, of these patients as low risk; 0% (n = 0) and 0.8% (n = 1) had a MACE, respectively. Sensitivity, specificity, and negative predictive value for TIMI = 0 in the primary cohort were 100% (95% confidence interval [CI]: 98.5% to 100%), 23.1% (95% CI: 20.9% to 25.3%), and 100% (95% CI: 98.8% to 100%), respectively. Sensitivity, specificity, and negative predictive value for TIMI ≤1 in the primary cohort were 99.2 (95% CI: 97.1 to 99.8), 48.7 (95% CI: 46.1 to 51.3), and 99.7 (95% CI: 98.9 to 99.9), respectively. Sensitivity, specificity, and negative value for TIMI ≤1 in the secondary cohort were 99.4% (95% CI: 96.5 to 100), 46.5% (95% CI: 42.9 to 50.1), and 99.7% (95% CI: 98.4 to 100), respectively. Conclusions An early-discharge strategy using an hs-TnI assay and TIMI score ≤1 had similar safety as previously reported, with the potential to decrease the observation periods and admissions for approximately 40% of patients with suspected ACS. (Advantageous Predictors of Acute Coronary Syndromes Evaluation [APACE] Study, NCT00470587 ; A 2hr Accelerated Diagnostic Protocol to Assess patients with chest Pain symptoms using contemporary Troponins as the only biomarker [ADAPT]: a prospective observational validation study, ACTRN12611001069943 )

Pathology Queensland consists of a network of 34 laboratories spread throughout Queensland. In 2007, biochemistry testing was standardised state-wide with the introduction of Beckman Coulter analysers. Their accuTnI assay was used for measuring cardiac troponin I. Simultaneously, the Universal Definition of Myocardial Infarction, as defined in 2000, was introduced with a new cardiac troponin I cut-off level according to the 99 th percentile. A number of issues ensued. The diagnosis of myocardial infarction increased dramatically straining emergency and cardiology resources. Unexpectedly, randomly occurring false positive results (flyers) were identified that had a significant impact on clinical intervention. ‘Highly sensitive' cardiac troponin assays were introduced into the market adding to the conundrum. We report more than 300 000 cardiac troponin I tests annually. Our experience with cardiac troponin testing will be presented as well as our research findings into the performance of troponin assays. Unlike our fictional Hitchhiker's Guide we have pursued analytical performance relentlessly. We have characterised assay robustness and between-assay variance, and presented guidance on how to universally define significant changes in serial cardiac troponin results. I will entertain our perspective regarding the value of ‘highly sensitive' cardiac troponin.

Background Bronchiectasis unrelated to cystic fibrosis (CF) is being increasingly recognized in children and adults globally, both in resource-poor and in affluent countries. However, high-quality evidence to inform management is scarce. Oral amoxycillin-clavulanate is often the first antibiotic chosen for non-severe respiratory exacerbations, because of the antibiotic-susceptibility patterns detected in the respiratory pathogens commonly associated with bronchiectasis. Azithromycin has a prolonged half-life, and with its unique anti-bacterial, immunomodulatory, and anti-inflammatory properties, presents an attractive alternative. Our proposed study will test the hypothesis that oral azithromycin is non-inferior (within a 20% margin) to amoxycillin-clavulanate at achieving resolution of non-severe respiratory exacerbations by day 21 of treatment in children with non-CF bronchiectasis. Methods This will be a multicenter, randomized, double-blind, double-dummy, placebo-controlled, parallel group trial involving six Australian and New Zealand centers. In total, 170 eligible children will be stratified by site and bronchiectasis etiology, and randomized (allocation concealed) to receive: 1) azithromycin (5 mg/kg daily) with placebo amoxycillin-clavulanate or 2) amoxycillin-clavulanate (22.5 mg/kg twice daily) with placebo azithromycin for 21 days as treatment for non-severe respiratory exacerbations. Clinical data and a parent-proxy cough-specific quality of life (PC-QOL) score will be obtained at baseline, at the start and resolution of exacerbations, and on day 21. In most children, blood and deep-nasal swabs will also be collected at the same time points. The primary outcome is the proportion of children whose exacerbations have resolved at day 21. The main secondary outcome is the PC-QOL score. Other outcomes are: time to next exacerbation; requirement for hospitalization; duration of exacerbation, and spirometry data. Descriptive viral and bacteriological data from nasal samples and blood inflammatory markers will be reported where available. Discussion Currently, there are no published randomized controlled trials (RCT) to underpin effective, evidence-based management of acute respiratory exacerbations in children with non-CF bronchiectasis. To help address this information gap, we are conducting two RCTs. The first (bronchiectasis exacerbation study; BEST-1) evaluates the efficacy of azithromycin and amoxycillin-clavulanate compared with placebo, and the second RCT (BEST-2), described here, is designed to determine if azithromycin is non-inferior to amoxycillin-clavulanate in achieving symptom resolution by day 21 of treatment in children with acute respiratory exacerbations. Trial registration Australia and New Zealand Clinical Trials Register (ANZCTR) number http://ACTRN12612000010897. http://www.anzctr.org.au/trial_view.aspx?id=347879

index admission. 313 (19.7%) patients had an elevated hscTnI value at 0 or 2 h and 494 (31.1%) patients had an elevated hs-cTnT value. Sensitivity for AMI was equivalent between hs-cTnI and hs-cTnT (96.2% versus 94.8%, p= 0.61). Specificity for AMI was higher using hs-cTnI at zero (93.6% versus 80.5%, p< 0.01) and two hours (92.8% vs. 80.8%, p< 0.01). Conclusions: The hs-cTnI and hs-cTnT assays were equally sensitive forearlydiagnosisofAMIbut thehs-cTnI assay was significantly more specific. http://dx.doi.org/10.1016/j.hlc.2013.05.494

Adenosine deaminase (ADA) activity is increased in effusions caused by certain clinical conditions including tuberculosis and bacterial infections. In this study, the ADA isoenzyme patterns in tuberculous and parainfective effusions were investigated to determine the isoenzyme responsible for this increase in activity. Fifty-one tuberculous effusions and six parainfective effusions were investigated. All effusions had increased ADA activity (median values of 126 and 127 units/L, respectively). In the tuberculous effusions, ADA2 isoenzyme was found to be primarily responsible for total activity, with a median contribution of 88 percent. The ADA1 (both ADA1m and ADA1c isoenzymes) was the major isoenzyme in the parainfective effusions with a median contribution of 70 percent. The ADA2 isoenzyme activity most likely reflects monocyte-macrophage turnover or activity, while ADA1 probably originates from lymphocytes or neutrophils. It is therefore essential to determine the isoenzyme profile when interpreting ADA activity levels in effusions. The measurement of the individual isoenzymes will enhance the diagnostic utility of ADA activity determinations in pleural effusions.

OBJECTIVE To evaluate the diagnostic potential of the ADA(T), ADA isoenzymes (ADA1 and ADA2) and the interferon-gamma (IFN-gamma) test in HIV-seropositive patients with tuberculous peritonitis. METHODS Ascitic ADA(T), ADA1, ADA2 and IFN-gamma were prospectively evaluated in HIV-seronegative patients with tuberculous peritonitis (n = 17), HIV-seropositive patients with tuberculous peritonitis (n = 6) and in patients with cirrhosis (n = 22) and malignancy (n = 5). RESULTS ADA(T) and ADA2 isoenzyme activities of HIV-seronegative (ADA(T) = 109 U/l; ADA2 = 94 U/l) and HIV-seropositive (ADA(T) = 109.5 U/l; ADA2 = 95.5 U/l) patients with tuberculous peritonitis, respectively, were significantly different (P < 0.001) from patients with cirrhosis (ADA(T) = 10.5 U/l; ADA2 = 8 U/l) and malignancy (ADA(T) = 13 U/l; ADA2 = 11 U/l). There was no significant difference in ADA(T) and ADA2 activities between HIV-seropositive and seronegative patients with tuberculous peritonitis. There was no significant correlation between ADA, its isoenzymes and IFN-gamma. CONCLUSIONS The diagnosis of tuberculous peritonitis can be made by a sensitive, relatively non-invasive procedure in both HIV-seronegative and seropositive patients with minimal risk to the patient and the investigator. The diagnostic value of ADA(T) is not enhanced by measuring ADA isoenzymes or IFN-gamma.

The molecular forms of adenosine deaminase (ADA) were studied in pleural effusions with high ADA activity. The molecular forms were separated by polyacrylamide gel electrophoresis (PAGE), and the molecular masses estimated by gel filtration. Effusions investigated were: tuberculosis (TB) (20 cases), lymphoma (3 cases), chronic myelogenous leukemia (1 case) and empyema (6 cases). Two ADA forms were identified, a small form (Smf-ADA) and a large form (Lmf-ADA). Without exception, the tuberculous effusions have shown only Lmf-ADA. All the other effusions contained both forms, the Smf-ADA being predominant. This was also the ADA pattern seen in normal lymphocytes. These findings may indicate different mechanisms of ADA release or origins of ADA in the various effusions. The Lmf-ADA may be secreted by activated T cells in TB, which would confirm the notion that ADA activity reflects cellular immunity. In contrast, in the nontuberculous cases the ADA probably leaked from damaged lymphocytes or neutrophils, hence the reflection of the cellular ADA pattern. The PAGE pattern may also be of value in distinguishing between TB and these other causes of high pleural fluid ADA.

The performance of highly sensitive troponin assays in the early detection of acute myocardial infarction (AMI) in patients presenting to the emergency department (ED) with chest pain is assay-dependent. The aim was to compare the diagnostic accuracy for AMI of highly sensitive troponin I (hsTnl)