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Noninvasive serum biomarkers (nonalcoholic fatty liver disease fibrosis score [NFS], fibrosis 4 score [FIB-4], or enhanced liver fibrosis [ELF] test) are recommended as first-line tools to determine the risk of advanced fibrosis in nonalcoholic fatty liver disease. We aimed to assess the utility of a pragmatic approach to screening for clinically significant fibrosis in primary care and diabetes clinics. We recruited 252 patients from an endocrine clinic or primary care facility. Anthropometric measurements, ELF test, ultrasound, and liver stiffness measurements (LSMs) were performed. Clinically significant fibrosis was defined as LSM ≥8.2 kPa or ELF ≥9.8. A subgroup of patients underwent liver biopsy (n = 48) or had imaging diagnostic of cirrhosis (n = 14). Patients were 57.3 ± 12.3 years old with a high prevalence of metabolic syndrome (84.5%), type 2 diabetes (82.5%), and body mass index (BMI) ≥40 kg/m2 (21.8%). LSM met quality criteria in 230 (91.3%) patients. NFS and FIB-4 combined had a high negative predictive value (90.0%) for excluding LSM ≥8.2 kPa. However, 84.1% of patients had indeterminate or high NFS or FIB-4 scores requiring further assessment. LSM ≥8.2 kPa and ELF ≥9.8 were present in 31.3% and 28.6% of patients, respectively. Following adjustment for age, BMI, sex, and presence of advanced fibrosis, older age was independently associated with ELF ≥9.8 (adjusted odds ratio, 1.14; 95% confidence interval, 1.06-1.24), whereas increasing BMI was independently associated with LSM ≥8.2 kPa (adjusted odds ratio, 1.15; 95% confidence interval, 1.01-1.30). Concordant LSM

Background Non-alcoholic fatty liver disease (NAFLD) is a common cause of incidental liver test abnormalities. General practitioners have a key role in identifying people with NAFLD at risk of significant liver disease. Recent specialist guidelines emphasize the use of fibrosis algorithms or serum biomarkers rather than routine liver tests, to assess advanced fibrosis. This study evaluated primary care clinicians’ current approach to diagnosis, management and referral of NAFLD. Methods A cross-sectional survey of primary care clinicians was undertaken through a structured questionnaire about NAFLD. A convenience sample of general practice clinics and general practice conferences in Metropolitan Brisbane and regional south east Queensland was selected. Results 108 primary care clinicians completed the survey (participation rate 100%). Fifty-one percent of respondents considered the prevalence of NAFLD in the general population to be ≤10%. Twenty-four percent of respondents felt that liver enzymes were sufficiently sensitive to detect underlying NAFLD. Most respondents were unsure whether the FIB-4 score (62.7% unsure) or ELF score (63.7% unsure) could help to identify advanced fibrosis or cirrhosis. Although 47% of respondents said they would refer a patient to a Gastroenterologist/Hepatologist if they suspect the patient has NAFLD, 44.1% do not make any referrals. Of concern, 70.6% of clinicians said they were unlikely to refer a patient to Hepatology unless liver function tests are abnormal. Conclusions Our findings demonstrate that many primary care clinicians underestimate the prevalence of NAFLD and under-recognise the clinical spectrum of NAFLD and how this is assessed.

The ACTH1–24 stimulation test is commonly used to assess the hypothalamic-pituitary-adrenal (HPA) axis. Given variations in CBG concentration and binding affinity, serum total cortisol may misclassify some patients. Salivary cortisol correlates well with serum free cortisol but is easier to measure and widely available in commercial laboratories. The aim of this study was to investigate the utility of measuring salivary cortisol during the ACTH1–24 stimulation test. Case–control study in a clinical research facility. Eighty-seven patients with suspected cortisol deficiency, twenty-four healthy controls, and ten healthy women on the oral contraceptive (OC) underwent an intravenous 250 µg ACTH1–24 stimulation test. Concordance of ACTH1–24 stimulated serum and salivary cortisol was evaluated. There was a significant difference in serum cortisol between the healthy volunteers and the women on the OC (P

Different biochemical markers exist in both blood and urine for assessing renal function. Most of these biomarkers have advantages and limitations associated with their use, which is important to consider when ordering and utilising them in the clinical setting. The ideal marker should be able to detect acute kidney injury (AKI) at the onset and be used for the diagnosis and ongoing monitoring and management of kidney disease. The search for such a marker is ongoing, as all potential candidates thus far are associated with certain limitations. This article will attempt to compare and contrast established and emerging kidney disease markers.

Aim. To examine the association between lifetime alcohol consumption and significant liver disease in type 2 diabetic patients with NAFLD. Methods. A cross-sectional study assessing 151 patients with NAFLD at risk of clinically significant liver disease. NAFLD fibrosis severity was classified by transient elastography; liver stiffness measurements ≥8.2 kPa defined significant fibrosis. Lifetime drinking history classified patients into nondrinkers, light drinkers (always ≤20 g/day), and moderate drinkers (any period with intake >20 g/day). Result. Compared with lifetime nondrinkers, light and moderate drinkers were more likely to be male (p=0.008) and to be Caucasian (p=0.007) and to have a history of cigarette smoking (p=0.000), obstructive sleep apnea (p=0.003), and self-reported depression (p=0.003). Moderate drinkers required ≥3 hypoglycemic agents to maintain diabetic control (p=0.041) and fibrate medication to lower blood triglyceride levels (p=0.044). Compared to lifetime nondrinkers, light drinkers had 1.79 (95% CI: 0.67–4.82; p=0.247) and moderate drinkers had 0.91 (95% CI: 0.27–3.10; p=0.881) times the odds of having liver stiffness measurements ≥8.2 kPa (adjusted for age, gender, and body mass index). Conclusions. In diabetic patients with NAFLD, light or moderate lifetime alcohol consumption was not significantly associated with liver fibrosis. The impact of lifetime alcohol intake on fibrosis progression and diabetic comorbidities, in particular obstructive sleep apnea and hypertriglyceridemia, requires further investigation.

Background & Aims There is limited knowledge regarding the longitudinal utility of biomarkers of fibrosis, such as the nonalcoholic fatty liver disease (NAFLD) fibrosis score (NFS) or the fibrosis-4 score (FIB-4) score. We examined longitudinal changes in the NFS and the FIB-4 score in patients with NAFLD, with and without clinically significant fibrosis (CSF). Methods We performed a retrospective study of 230 patients with NAFLD, collecting clinical and laboratory records to calculate NFS and FIB-4 scores at 6 monthly intervals for 5 years before hepatology assessment of fibrosis. Linear mixed models with random intercept and slope and adjusted for age at baseline were used to assess the progression of NFS and log-transformed FIB-4 scores over time in subjects with and without CSF, determined by liver stiffness measurements of 8.2 kPa or greater. Results Patients had a median of 11 (minimum, 10; maximum, 11) retrospective observations over a median time period of 5 years (minimum, 4.5 y; maximum, 5 y). Of patients with low baseline NFS and FIB-4 scores, 31.11% and 37.76%, respectively, had CSF at the time of hepatology assessment. There was a correlation between NFS and log10 FIB-4 over time (repeated measure r = 0.55; 95% CI, 0.52–0.59). The rate of increase in NFS and log10 FIB-4 was significantly higher in patients with than without CSF (both P Conclusions Noninvasively measured fibrosis scores increase progressively in patients with NAFLD and CSF. Further studies are needed to determine whether repeated measurements can identify patients at risk for CSF.

Aims To examine the relationship between steatosis quantified by controlled attenuation parameter (CAP) values and glycaemic/metabolic control. Methods 230 patients, recruited from an Endocrine clinic or primary care underwent routine Hepatology assessment, with liver stiffness measurements and simultaneous CAP. Multivariable logistic regression was performed to identify potential predictors of Metabolic Syndrome (MetS), HbA1c ≥ 7%, use of insulin, hypertriglyceridaemia and CAP ≥ 300 dB/m. Results Patients were 56.7 ± 12.3 years of age with a high prevalence of MetS (83.5%), T2DM (81.3%), and BMI ≥ 40 kg/m2 (18%). Median CAP score was 344 dB/m, ranging from 128 to 400 dB/m. BMI (aOR 1.140 95% CI 1.068–1.216), requirement for insulin (aOR 2.599 95% CI 1.212–5.575), and serum ALT (aOR 1.018 95% CI 1.004–1.033) were independently associated with CAP ≥ 300 dB/m. Patients with CAP interquartile range Conclusions Our data demonstrate that an elevated CAP reflects suboptimal metabolic control. In diabetic patients with NAFLD, CAP may be a useful point-of-care test to identify patients at risk of poorly controlled metabolic comorbidities or advanced diabetes.

Supplemental Digital Content is available in the text, An observational study describing the number and type of chronic conditions and medications taken by diabetic patients with NAFLD and identifying characteristics that may impact liver disease severity or clinical management. Adults with type 2 diabetes have a high prevalence of nonalcoholic fatty liver disease (NAFLD) and increased risk of developing advanced liver disease. Appropriate management should consider the characteristics of the diabetic NAFLD population, as comorbid conditions and medications may increase the complexity of treatment strategies. Diabetic patients with NAFLD at risk of clinically significant liver disease (as assessed by the FIB-4 or NAFLD fibrosis scores) were recruited consecutively from the Endocrine clinic or primary care. Medical conditions, medication history, anthropometric measurements, and laboratory tests were obtained during assessment. NAFLD severity was classified by transient elastography and liver ultrasound into “no advanced disease” (LSM < 8.2 kPa) or “clinically significant liver disease” (LSM ≥ 8.2 kPa). The most common coexistent chronic conditions were metabolic syndrome (94%), self-reported “depression” (44%), ischaemic heart disease (32%), and obstructive sleep apnoea (32%). Polypharmacy or hyperpolypharmacy was present in 59% and 31% of patients respectively. Elevated LSM (≥ 8.2 kPa) suggesting significant liver disease was present in 37% of this at-risk cohort. Increasing obesity and abdominal girth were both independently associated with likelihood of having significant liver disease. There is a high burden of multimorbidity and polypharmacy in diabetic NAFLD patients, highlighting the importance of multidisciplinary management to address their complex health care needs and ensure optimal medical treatment.

Background:Current commercial tubes have difficulties in producing “true” serum from all blood samples even within the recommended clotting times. Hence, Becton Dickinson (BD) and now Greiner have produced tubes containing thrombin as the procoagulant to reduce the clotting time and increase the possibility of producing serum from anticoagulated blood samples.Methods:The Greiner BCA Fast Clot (GBBCAFC) tube was evaluated in a hospital environment using 40 participants, (30 healthy and 10 undergoing renal dialysis) for 32 analytes against the Greiner lithium heparin tube and the BD Rapid Serum Tubes (BD RST) tube measured on Beckman DxC 800 and DxI 800 analyzers. Clotting strength was also examined using thromboelastography (TEG).Results:The analytes results showed there was a very close agreement between the BD RST tube and GBBCAFC tube in comparison with lithium heparin plasma. The result comparison data showed equivalent performance with lower levels of hemolysis. The prolonged storage study also showed very similar agreement between the BD RST and the GBBCAFC tubes. Likewise, the TEG data showed there was very little difference in clotting ability between the tubes, and neither was capable of producing true serum from blood spiked with 2 U heparin/mL of blood.Conclusions:The study showed the GBBCAFC tube with the combination of the two procoagulants blood clotting activator and thrombin produced comparable performance with the lithium heparin plasma and the BD RST serum samples.

Introduction: Gentamicin due to its low level of resistance and rapid bactericidal activity is commonly used to treat gram-negative bacteria. However, due to its toxic effects it needs to be monitored. To date, no interference has been reported with gentamicin assays. Materials and methods: A patient with leg cellulitis and sepsis received a single dose of gentamicin and a sample was sent for gentamicin analysis. The sample showed high blank absorbance readings on Beckman DxC800 and DC800 analysers with various dilutions. A second sample was received and analysed on a Roche Cobas system to obtain a result. A third sample was received 107 hours later with the same results and this sample was then analysed neat and post ethanol precipitation on all the turbidimetric assays available on the DxC800 analyser. Results: The high blank absorbance was observed upon addition of the reactive reagents due to protein precipitation. Although not obvious from the patient protein results, it was shown the presence of high IgM paraprotein, 18.9 g/L (reference range 0.4-2.3 g/L) was the cause of precipitation, giving high blank readings. Of all the other turbidimetric assays, only vancomicin and valproate showed similar high blank absorbance readings. To be able to provide more rapid results it was shown ethanol could be used as a precipitant of proteins in both calibrators and patient samples with acceptable recovery. Conclusion: IgM paraprotein was identified as the cause of interference with the gentamicin, vancomicin and valproate assays. Protein interference in these assays can be overcome by precipitation with ethanol.

ObjectivesGlucose is one of the most frequently measured analytes in laboratories. Most recent studies on glucose stabilities confirm that the sodium fluoride/potassium oxalate (NaF/KOx) tube is far from the gold standard. Citrate tubes have been suggested as the preferred tube type by many institutions. Greiner has introduced a glucose-specific tube (Glucomedics) containing NaF/KOx, citrate, and EDTA to minimise glycolysis. The aim was to determine which tube would be the most suitable for accurate glucose estimation in a routine laboratory setting.Design and methodsThe study process involved three experiments: (a) participant comparison using lithium heparin plasma as the comparative sample; (b) stability study (0, 1, 2 and 4 h); and (c) minimal fill volume for the citrate and the Glucomedics tubes.ResultsThe patient comparison study of lithium heparin plasma showed that EDTA, NaF/KOx, and both citrate and Glucomedics if corrected for dilutional factors produced acceptable results. The stability study up to 4 h showed that the Glucomedics tube was most effective in preventing clinically significant change in glucose concentration at a room temperature. Both citrate and Glucomedics need to be filled within 0.5 mL of the recommended fill volume for acceptable results.ConclusionThe Glucomedics tube is the most suitable for minimising glycolysis. Further improvements to it (use of correct dilutional factor and the addition of gel separator) would make this tube the benchmark for the most accurate estimation, best diagnosis and patient care decisions.

To the Editor,A 58-year-old female presented post overdose of an unknown amount of digoxin 62.5 µg tablets. A level taken 6 h post ingestion was 10 µg/L (therapeutic range 0.8–2.0 µg/L). The patient was bradycardiac 36/min, and was administered five vials of DigiFab (DigiFab, Pherba, Sydney, NSW, Australia). Our digoxin method, Beckman Coulter on the DxC800 general chemistry ana-lyser (Beckman Coulter, Brea, CA, USA) is not suitable for digoxin estimation in the presence of DigiFab due to posi-tive interference.Digoxin continues to be prescribed for the treatment of cardiac disorders, most frequently atrial fibrillation [1]. Digoxin toxicity usually occurs in the context of renal impairment, but as in our case, can be due to deliberate overdose [2]. Additionally related compounds digitoxin, oleander, Chinese herbal medicines (Chan Su, Lu-Shen-wan), spironolactone, etc can contribute or independently produce digoxin toxicity [3]. It is estimated in the USA that 0.4% of all hospital admissions, 1.1% of outpatients and 10%–18% of nursing care residents suffer digoxin toxicity and this is on the decrease [2]. Digibind digoxin-specific antibodies or antidigoxin Fab fragments DigiFab (of ovine origin) are available for life threatening symptoms of severe toxicity. Recommendation for use of both antidotes is identical. Once these antidotes are administered it can be difficult to obtain accurate free digoxin concentrations on a large number of general chemistry or immunoassay analysers. McMillan et al. evaluated 13 methods designed to quantify free digoxin and reported 4/13 showed marked positive interference, 5/13 showed moderate and four methods showed minimal interference [4]. Removing the effect of digoxin Fab fragments can aid decisions regard-ing additional dosing, as well as determining the correct time to recommence digoxin therapy. Manufacturers method inserts indicate that routine methods are not suit -able for digoxin estimation when Digibind is used. Ultra-filtration of the sample to remove the Digibind or DigiFab is a method for eliminating interference. However, ultra-filtration methods are not standardised and may require matrix-specific calibrators and lengthen turn-around-times [4].Here we describe a protein precipitation method that will provide accurate free digoxin concentrations in the presence of the antidotes. Polyethylene glycol (PEG) is non-denaturing water soluble polymer that precipitates proteins [5]. This permits proteins and bound compounds to be removed, providing a supernatant of unbound com-pounds. To determine if this method is suitable for meas-uring free digoxin post DigiFab administration, samples were treated with PEG to remove the DigiFab and its bound digoxin, specifically to DigiFab. PEG concentration was 24 g/100 mL (Fluka#812160, polyethylene glycol 6000, Sigma Aldrich). Samples were mixed with equal volumes of the PEG solution (0.5 mL:0.5 mL), vortex mixed, than centrifuged (5 min, 3000

Background Availability of whole blood creatinine estimation for patients scheduled to undergo radiological contrast investigations can provide information to aid patient care by reducing adverse effects and improving departmental efficiencies. Methods We performed imprecision studies, different patient sample type comparison in 40 participants, and a limited interference study with dopamine and dobutamine on the i-Stat and StatStrip point-of-care enzymatic analysers with the Beckman DxC800 Jaffe assay. Results Imprecision results showed that the i-Stat performed better. Patient comparison data indicated that the i-Stat provided better correlation than the StatStrip for all the different sample types with correlation coefficients (r2) being 0.995-0.996 and 0.918-0.995, respectively. The i-Stat results had a small positive bias of 6-9% for the three different sample types, which required different reference intervals. The StatStrip method showed greater scatter and overall small negative bias of 26% for the whole blood samples and a 10% positive bias with the plasma samples. Dopamine caused significant positive interference with the i-Stat only while dobutamine caused a small negative bias with the StatStrip method only. Conclusions The findings indicated there are differences offered by the two systems. The StatStrip requires a very small finger prick capillary sample, calculates estimation of the glomerular filtration rate and has an adjustment option to improve correlation with the local method. The i-Stat offers better analytical imprecision and patient comparison with the laboratory method with the three sample types but showed significant interference from dopamine. A final consideration was the availability of middleware to capture patient results with the i-Stat. Based on all the study data, the i-Stat was recommended.

1 Pathology Queensland , Chemical PathologyPrincess Alexandra Hospital, Brisbane , Australia 2 School of Medicine , Southside Clinical School, The University of Queensland, Brisbane , Australia 3 Pathology Queensland , HaematologyPrincess Alexandra Hospital, Brisbane , Australia Keywords: HbA

We determined the prevalence of iron overload due to homozygous haemochromatosis in an asymptomatic Australian (predominantly Caucasian) population by surveying 1968 employees of two large corporations. Subjects were screened by measurement of transferrin saturation and serum ferritin concentration and, in all subjects with elevation of both indices, percutaneous liver biopsy was performed to establish whether significant iron overload was present. The prevalence of iron overload due to haemochromatosis in this population was 0.36%. The prevalence rate was not significantly different between males and females, suggesting that this autosomal recessive disease is expressed equally in females given an adequate dietary iron supply. The positive predictive value of a transferrin saturation consistently greater than 45% together with an elevated serum ferritin concentration was 64%. It is concluded that the prevalence of significant iron overload due to homozygous haemochromatosis warranting treatment is approximately 1:300 and that transferrin saturation should be included in existing adult health screening programmes.

We report the use of hair roots and buccal cells as specimens of choice for DNA analysis of genetic diseases in a service laboratory. Our protocols using these specimen types show superiority to those using blood specimens in the areas of collection, transport, storage and overall cost. Our experience using these specimen types for 319 cystic fibrosis ΔF508 mutation tests and 62 Leber's hereditary optic neuroretinopathy mutation tests leads us to recommend that hair roots and buccal cells should be evaluated as specimens of first choice when developing PCR DNA analysis.