BACKGROUND:Hyperkalaemia is managed in the emergency department (ED) following measurement of potassium results by blood gas analysers (BGA) or laboratory analysers (LAB). AIMS:To determine the prevalence of clinically significant differences between BGA and LAB potassium results and the impact on ED hyperkalaemia management. METHODS:Retrospective analysis of time-matched ED BGA and LAB potassium samples from 2019 to 2020 (taken within 15 min, one or both results ≥6.0 mmol/L). Mean differences and 95% limits of agreement (LoA) were determined for pairs with one or both results ≥6.0 mmol/L and a separate 500 consecutive sample pairs. RESULTS:Four hundred eighty-eight matched BGA and LAB samples met the inclusion criteria. Of these, 201 (41.2%) differed by ≤0.5 mmol/L, 169 (34.6%) included a haemolysed LAB sample, and 12 (2.5%) had an unreportable BGA sample. One hundred six (21.7%) pairs differed by >0.5 mmol/L, and 60/106 (57%) had normal LAB potassium results, but BGA indicated moderate/severe hyperkalaemia (two of these pairs received hyperkalaemia treatment). Of patients with a haemolysed LAB sample, or where pairs differed by >0.5 mmol, 48 were treated with insulin and five (10.4%) experienced hypoglycaemia. Mean differences and LoA for pairs with LAB results <6.0 mmol/L but BGA ≥6.0 mmol/L demonstrated unacceptable agreement, with 18 (25.7%) BGA results exceeding 8.0 mmol/L. CONCLUSIONS:Potentially significant discordance may occur between BGA and LAB potassium results. Clinicians need to be aware of factors impacting both analytical methods' accuracy (such as poor venepuncture or sample handling, (K) EDTA interference) and undetectable haemolysis with BGA measurements. We recommend BGA hyperkalaemia be confirmed with LAB results using a non-haemolysed sample where time permits.

Background: Electrophoretic quantification of paraproteins varies between laboratories, particularly for paraproteins that co-migrate with normal beta-region proteins. To reduce inter-laboratory variability, new guidelines for standardised reporting recommend quantitating beta-migrating paraproteins with the entire beta-region.1 For laboratories currently quantitating beta-1 and beta-2 migrating paraproteins separately, paraprotein estimations are likely to increase on total beta-quantification, but the magnitude of this has not been assessed. Aim: To compare measurement of beta-migrating paraproteins using total beta-quantification to that of beta-1 or beta-2 quantification. Methods: Beta-migrating paraproteins were re-quantitated retrospectively in 6 months of capillary zone electrophoresis data. Results: Of 2054 paraproteins examined, 175 (8.5%) migrated in the beta-region. When re-quantitated with the total beta-region, the median increase in beta-1 and beta-2 migrating paraprotein concentration was 2.0 g/L (IQR 1.6,2.5) and 4.2 g/L (IQR 3.4,4.9) respectively. For small paraproteins, this represented two- to three-fold increases in paraprotein concentration. Discussion: Adoption of total beta-quantification may significantly increase estimated paraprotein concentrations. This is most conspicuous for bands migrating in the beta-2 region but also significant for beta-1 migrating proteins. For both, impact is greatest with small paraproteins. Such increases may be interpreted as progression of disease and trigger further investigations. References 1. Tate JR, Smith JD, Wijeratne N, et al. Proposed addendum to 2012 Recommendations for Standardised Reporting of Protein Electrophoresis in Australia and New Zealand. Clin Biochem Rev 2019; 40: 23–30.

Diagnostic investigations (pathology laboratory and medical imaging) aim to: increase certainty of the presence or absence of disease by supporting the process of differential diagnosis; support clinical management; and monitor a patient's trajectory (e. g., disease progression or response to treatment). Digital health can be defined as the collection, storage, retrieval, transmission, and utilization of data, information, and knowledge to support healthcare. Digital health has become an essential component of the diagnostic process, helping to facilitate the accuracy and timeliness of information transfer and enhance the effectiveness of decision-making processes. Digital health is also important to diagnostic stewardship, which involves coordinated guidance and interventions to ensure the appropriate utilization of diagnostic tests for therapeutic decision-making. Diagnostic stewardship and informatics are thus important in efforts to establish shared decision-making. This is because they contribute to the establishment of shared information platforms (enabling patients to read, comment on, and share in decisions about their care) based on timely and meaningful communication. This paper will outline key diagnostic informatics and stewardship initiatives across three interrelated fields: (1) diagnostic error and the establishment of outcomes-based diagnostic research; (2) the safety and effectiveness of test result management and follow-up; and (3) digitally enhanced decision support systems.

BACKGROUND:General medical wards admit a varied cohort of patients from the emergency department, some of whom deteriorate during their hospital stay. Currently, we use vital signs based warning scores to predict patients at risk of imminent deterioration, but there is now a growing body of literature that commonly available laboratory results may also help to identify those at risk.AIM:To assess whether a laboratory-based admission score can predict in hospital mortality, intensive care unit (ICU) admission, medical emergency team (MET) activation or cardiac arrest in a cohort of Australian general medical patients admitted through the emergency department (ED).METHODS:We performed a retrospective observational study of all general medical admissions to hospital through the ED in 2015. Admission pathology was used to calculate a risk score. In-patient outcomes of death, ICU transfer, MET call activation or cardiac arrest were collected from hospital records.RESULTS:We studied 2942 admissions derived from 2521 patients, with a median age of 81 years. There were 143 in-patient deaths, 82 ICU admissions, 277 MET calls and 14 cardiac arrest calls. The laboratory-based admission score had an area under the receiver operating characteristic curve (AUC-ROC) of 0.76 (95% confidence interval (CI): 0.72-0.80) for inpatient death, an AUC-ROC of 0.79 (95% CI: 0.66-0.93) for inpatient cardiac arrest, an AUC-ROC of 0.64 (95% CI: 0.58-0.70) for ICU transfer and an AUC-ROC of 0.59 (95% CI: 0.55-0.62) for MET call activation. When patients aged over 75 were analysed separately, the AUC-ROC for prediction of in-patient death was 0.74 (95% CI: 0.70-0.78) and increased to 0.86 (95% CI: 0.73-0.98) for the prediction of in-patient cardiac arrest.CONCLUSION:A simple laboratory-derived score obtained at patient admission is a fair to good predictor of subsequent in-patient death or cardiac arrest in general medical patients and in the older patient cohort. Prospective interventional studies are required to ascertain the clinical utility of this admission score.

A comparison of the clinical performance of the Elecsys Anti-SARS-CoV-2, Liaison SARS-CoV-2 S1/S2 IgG, Access SARS-CoV-2 IgG and Vitros Immunodiagnostic Products Anti-SARS-CoV-2 IgG immunoassays for the diagnosis of COVID-19 infection was performed. Patient sera were collected at least 6 weeks following onset of COVID-19 infection symptoms. Negative control specimens were stored specimens from those without COVID-19, collected in April-May 2019. Sensitivity and specificity with 95% confidence intervals (CI) were calculated. Linear regression was used to examine the relationship between the magnitude of serological response and clinical characteristics. There were 80 patients from whom 86 sera specimens were collected; six patients had duplicate specimens. There were 95 negative control specimens from 95 patients. The clinical sensitivity of the Elecsys assay was 98.84% (95% CI 93.69-99.97), specificity was 100% (95% CI 96.19-100.00); the Liaison assay clinical sensitivity was 96.51% (95% CI 90.14-99.27), specificity was 97.89% (95% CI 92.60-99.74); the Access assay clinical sensitivity was 84.88% (95% CI 75.54-91.70), specificity was 98.95% (95% CI 94.27-99.97); and the Vitros assay clinical sensitivity was 97.67% (95% CI 91.85-99.72), specificity was 100% (95% CI 96.15-100.00). A requirement for hospitalisation for COVID-19 infection was associated with a larger Vitros, Liaison and Access IgG response whilst fever was associated with a larger Elecsys response. All assays evaluated with the exception of the Access assay demonstrated similar performance. The Elecsys assay demonstrated the highest sensitivity and specificity.

BACKGROUND:Adrenal vein sampling (AVS) is crucial for accurate lateralization of aldosterone excess but it is technically challenging due to the difficulty of adrenal vein cannulation. The use of adrenocorticotropic hormone (ACTH) to improve cannulation success is controversial and can lead to discordant lateralization outcomes.OBJECTIVE:To evaluate the utility of ACTH in two centres with different levels of AVS expertise and formulate a strategy for interpreting discordant results.DESIGN:A retrospective cross-sectional analysis of AVS results and postoperative patient outcomes.SETTING:Two large tertiary hospitals with harmonized AVS protocols where adrenal venous samples are collected both before and after ACTH stimulation.MEASUREMENTS:Cannulation success (measured by selectivity index, SI), lateralization (measured by lateralization index, LI) and postoperative biochemical cure.RESULTS:Number of AVS procedures judged to have successful bilateral adrenal vein cannulation increased from 53% pre- to 73% post-ACTH. The increase in cannulation success was significantly higher in centre where AVS was performed by multiple radiologists with a lower basal success rate. In both centres, the proportion of cases deemed to display lateralization significantly decreased with the use of ACTH (70% pre- to 52% post-ACTH). Based on postoperative outcomes of patients with discordant results who underwent unilateral adrenalectomy, the combination of LI >3 pre-ACTH and LI >2 post-ACTH was predictive of a biochemical cure.CONCLUSION:Adrenocorticotropic hormone can increase the rate of cannulation success during AVS at the expense of reduced lateralization. The criteria for lateralization should be carefully determined based on local data when ACTH is used.

Malignant pleural mesothelioma (MPM) remains a deadly disease with limited therapeutic options beyond platinum/pemetrexed chemotherapy. Immune checkpoint inhibitors have demonstrated modest benefit in the second to later-line settings. An MPM patient from our institute developed myocarditis and myositis after 2 cycles of second-line nivolumab. Despite immunosuppression with corticosteroids and mycophenolate mofetil, there was ongoing rise in troponin levels which remained elevated for months. The patient developed an impressive but brief response following cessation of nivolumab. Myocarditis and myositis are rare complications of immune checkpoint inhibitors. Clinicians should be aware of these possible complications as myocarditis can result in mortality.

Objective: We aimed to determine the prevalence of preexisting dysglycaemia in inpatients admitted with acute coronary syndrome (ACS), their characteristics and, association with acute and 12-month clinical outcomes. Research Design and Methods: In this prospective observational cohort study, admission HbA1c testing was undertaken on consecutive inpatients aged ≥54 years admitted with ACS. Patients were categorised into those with diabetes (prior diagnosis or HbA1c ≥ 6.5%, ≥48mmol/mol), prediabetes (HbA1c 5.7-6.4%, 39-46mmol/mol) and no diabetes (HbA1c <5.6%, <38mmol/mol). Results: Between July 2013 and July 2015, 847 consecutive inpatients aged ≥54 years were admitted with ACS. 313 (37%) inpatients had diabetes, 312(37%) had prediabetes and 222(25%) had no diabetes. After adjusting for age, sex, smoking status and previous myocardial infarction, diabetes, as opposed to no diabetes, was associated with higher odds of Acute Pulmonary Oedema (APO) (OR 2.60, P<0.01), longer length of stay (LOS) (IRR 1.18, P=0.02) and, higher odds of 12-month ACS recurrence (OR 1.86, P<0.05). Prediabetes was not a statistically significant marker of adverse clinical outcomes. However, analysed as a continuous variable, every 1% (11 mmol/mol) increase in HbA1c was associated with increased odds of APO (OR 1.28, P=0.002) and, longer LOS (IRR 1.05, P=0.03). Conclusions: In our study, three-quarters of all inpatients aged ≥54 years admitted with ACS had preexisting dysglycaemia. Inpatients with diabetes had increased odds of APO, longer LOS and higher 12-month ACS recurrence. Higher HbA1c, was associated with increased odds of APO and longer LOS. Randomised studies with cardioprotective anti-hyperglycaemic agents are necessary in determining if improving dysglycaemia in ACS patients improves clinical outcomes. Disclosure D. Mahendran: None. G. Hamilton: None. J. Weiss: None. J. Lew: None. K. Khoo: None. E.I. Ekinci: None.

Aims: Using routine HbA1c measurement to determine the prevalence of diabetes mellitus (known and previously unrecognized) and their hospital outcomes among hematology and oncology inpatients. Methods: This was a prospective, observational study. Routine automated HbA1c testing was performed in all hematology and oncology inpatients aged >= 54 years at a tertiary hospital, July 2013-January 2015. The outcome measures were: (i) prevalence of known and previously unrecognized diabetes, and (ii) hospital outcomes: length-of-stay (LOS), intensivecare-unit (ICU) admission, 30-day/18-month readmission, and 18-month mortality. Results: Over the 18-month study period, 1076 inpatients aged >= 54 years were admitted to hematology (n = 298) and oncology (n = 778) units: 21% had known diabetes and 7% had previously unrecognized diabetes. Patients with known diabetes had a longer LOS (IRR: 1.18, 95% CI: 1.02-1.37, p = 0.03), compared to those without diabetes, adjusting for age, hemoglobin level, estimated-glomerular-filtration-rate, admission specialty unit, Charlson's comorbidity index score, and glucocorticoid exposure. No significant differences were observed in ICU admission, 30-day/18-month readmission, and 18-month mortality among patients with known, previously unrecognized and no diabetes (p >= 0.05). Conclusions: Approximately one in five hematology or oncology inpatients aged >= 54 years had known diabetes, and one in fourteen had previously unrecognized diabetes. Those with known diabetes had a longer hospital stay. Routine HbA1c measurement is can be useful for identifying previously unrecognized diabetes, particularly among patients with high glucocorticoid exposure. Further study is required to determine cost-effectiveness in screening for unrecognized diabetes and optimal management of these patients. (C) 2019 Elsevier B.V. All rights reserved.

AimsDiabetes is a major risk factor for stroke. We aimed to investigate the prevalence of diabetes and pre-diabetes within a stroke cohort and examine the association of glycaemia status with mortality and morbidity.MethodsInpatients aged ≥54 who presented with a diagnosis of stroke had a routine HbA1c measurement as part of the Austin Health Diabetes Discovery Initiative. Additional data were attained from hospital databases and Australian Stroke Clinical Registry. Outcomes included diabetes and pre-diabetes prevalence, length of stay, 6-month and in-hospital mortality, 28-day readmission rates, and 3-month modified Rankin scale score.ResultsBetween July 2013 and December 2015, 610 patients were studied. Of these, 31% had diabetes while 40% had pre-diabetes. Using multivariable regression analyses, the presence of diabetes was associated with higher odds of 6-month mortality (OR = 1.90, p = 0.022) and higher expected length of stay (IRR = 1.29, p = 0.004). Similarly, a higher HbA1c was associated with higher odds of 6-month mortality (OR = 1.27, p = 0.005) and higher expected length of stay (IRR = 1.08, p = 0.010).Conclusions71% of this cohort had diabetes or pre-diabetes. Presence of diabetes and higher HbA1c were associated with higher 6-month mortality and length of stay. Further research is necessary to determine if improved glycaemic control may improve stroke outcomes.

Acute severe ulcerative colitis (ASUC) is a medical emergency that requires prompt assessment and judicious management. IV corticosteroids are first-line therapy, but a significant proportion who do not improve after 3–7 days require salvage treatment or surgery. Management decisions are conventionally based on the Oxford criteria1 though recent data suggest that an Ulcerative Colitis Endoscopic Index of Severity (UCEIS) >6 and faecal calprotectin (FC) >1000 μg/g at Day 3 are markers of steroid failure. We report the results of a study which examined the association of steroid response with clinical activity, biomarkers and endoscopic findings at admission. A prospective cohort of inpatients with ASUC treated with IV steroids were recruited from 4 Australian hospitals and underwent clinical and endoscopic assessment. Bloods were assessed prior to IV steroids and FC prior to endoscopy. Steroid failure was defined if patients met the Oxford Day 3 or 7 criteria. Steroid responders did not meet these criteria. Statistical comparisons were made using Mann–Whitney U and Fisher's test. Area under the receiver operating curve analysis (AUROC) was performed to assess predictors of treatment. Forty-one patients were enrolled (18 female; median age 33.9 years (Q1–3 = 24.5–42.7)). Ten patients were steroid responsive; 31 were steroid refractory and received infliximab salvage therapy. Prior diagnosis of colitis, disease/flare duration or therapy history were not associated with outcome. The Lichtiger score, endoscopic activity, CRP, albumin and FC were significantly different between steroid failures and responders (Table 1). FC was predictive of steroid failure (AUROC = 0.89) with an optimal cut-off of 1395 μg/g (sensitivity of 89%, specificity of 63%, PPV of 67% and NPV 67%). CRP/Albumin ratio (CAR) was predictive of steroid failure (AUROC 0.89) with an optimal cut-off of 1.34 (sensitivity of 85%, specificity of 87%, PPV of 93% and NPV of 67%). The combination of FC >1395 μg/g and CAR >1.34 was strongly predictive of steroid failure (sensitivity 79% specificity 100% PPV 100% and NPV 62.5%). Steroid failures vs. steroid responders (data expressed as median (Q1–3) or n (%). Steroid failures vs. steroid responders (data expressed as median (Q1–3) or n (%). Early faecal and blood biomarkers are useful in stratifying patients at risk of steroid failure. All patients with an FC >1395 μg/g and CAR >1.34 were steroid refractory. Implementation of such risk factors may allow early identification of patients for whom steroid therapy is likely to be futile and expedite the initiation of salvage therapy. 1. Travis SP, Farrant JM, Ricketts C, et al. Predicting outcome in severe ulcerative colitis. Gut, 1996.

OBJECTIVE Limited studies have examined the association between diabetes and HbA1c with postoperative outcomes. We investigated the association of diabetes, defined categorically, and the association of HbA1c as a continuous measure, with postoperative outcomes. RESEARCH DESIGN AND METHODS In this prospective, observational study, we measured the HbA1c of surgical inpatients age ≥54 years at a tertiary hospital between May 2013 and January 2016. Patients were diagnosed with diabetes if they had preexisting diabetes or an HbA1c ≥6.5% (48 mmol/mol) or with prediabetes if they had an HbA1c between 5.7 and 6.4% (39 and 48 mmol/mol). Patients with an HbA1c <5.7% (39 mmol/mol) were categorized as having normoglycemia. Baseline demographic and clinical data were obtained from hospital records, and patients were followed for 6 months. Random-effects logistic and negative binomial regression models were used for analysis, treating surgical units as random effects. We undertook classification and regression tree (CART) analysis to design a 6-month mortality risk model. RESULTS Of 7,565 inpatients, 30% had diabetes, and 37% had prediabetes. After adjusting for age, Charlson comorbidity index (excluding diabetes and age), estimated glomerular filtration rate, and length of surgery, diabetes was associated with increased 6-month mortality (adjusted odds ratio [aOR] 1.29 [95% CI 1.05–1.58]; P = 0.014), major complications (1.32 [1.14–1.52]; P < 0.001), intensive care unit (ICU) admission (1.50 [1.28–1.75]; P < 0.001), mechanical ventilation (1.67 [1.32–2.10]; P < 0.001), and hospital length of stay (LOS) (adjusted incidence rate ratio [aIRR] 1.08 [95% CI 1.04–1.12]; P < 0.001). Each percentage increase in HbA1c was associated with increased major complications (aOR 1.07 [1.01–1.14]; P = 0.030), ICU admission (aOR 1.14 [1.07–1.21]; P < 0.001), and hospital LOS (aIRR 1.05 [1.03–1.06]; P < 0.001). CART analysis confirmed a higher risk of 6-month mortality with diabetes in conjunction with other risk factors. CONCLUSIONS Almost one-third of surgical inpatients age ≥54 years had diabetes. Diabetes and higher HbA1c were independently associated with a higher risk of adverse outcomes after surgery.

Individual laboratories are required to compose an alert list for identifying critical and significant risk results. The high-risk result working party of the Royal College of Pathologists of Australasia (RCPA) and the Australasian Association of Clinical Biochemists (AACB) has developed a risk-based approach for a harmonized alert list for laboratories throughout Australia and New Zealand. The six-step process for alert threshold identification and assessment involves reviewing the literature, rating the available evidence, performing a risk analysis, assessing method transferability, considering workload implications and seeking endorsement from stakeholders. To demonstrate this approach, a worked example for deciding the upper alert threshold for potassium is described. The findings of the worked example are for infants aged 0-6 months, a recommended upper potassium alert threshold of >7.0 mmol/L in serum and >6.5 mmol/L in plasma, and for individuals older than 6 months, a threshold of >6.2 mmol/L in both serum and plasma. Limitations in defining alert thresholds include the lack of well-designed studies that measure the relationship between high-risk results and patient outcomes or the benefits of treatment to prevent harm, and the existence of a wide range of clinical practice guidelines with conflicting decision points at which treatment is required. The risk-based approach described presents a transparent, evidence- and consensus-based methodology that can be used by any laboratory when designing an alert list for local use. The RCPA-AACB harmonized alert list serves as a starter set for further local adaptation or adoption after consultation with clinical users.

Background: 2017 ATA guidelines recommend using trimester- and method-specific TSH reference intervals defined in local populations. We used the transference technique on the Roche TSH intervals to other common methods.

Background: Thiamine has a crucial role in energy production, and consequently thiamine deficiency (TD) has been associated with cardiac failure, neurological disorders, oxidative stress (lactic acidosis and sepsis) and refeeding syndrome (RFS). This review aims to explore analytical methodologies of thiamine compound quantification and highlight similarities, variances and limitations of current techniques and how they may be relevant to patients. Content: An electronic search of Medline, PubMed and Embase databases for original articles published in peerreviewed journals was conducted. MethodsNow was used to search for published analytical methods of thiamine compounds. Keywords for all databases included "thiamine and its phosphate esters", "thiamine methodology" and terms related to critical illness. Enquiries were also made to six external quality assurance (EQA) programme organisations for the inclusion of thiamine measurement. Summary: A total of 777 published articles were identified; 122 were included in this review. The most common published method is HPLC with florescence detection. Two of the six EQA organisations include a thiamine measurement programme, both measuring only whole-blood thiamine pyrophosphate (TPP). No standard measurement procedure for thiamine compound quantification was identified. Outlook: Overall, there is an absence of standardisation in measurement methodologies for thiamine in clinical care. Consequently, multiple variations in method practises are prohibiting the comparison of study results as they are not traceable to any higher order reference. Traceability of certified reference materials and reference measurement procedures is needed to provide an anchor to create the link between studies and help bring consensus on the clinical importance of thiamine.