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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: 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.

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.)

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.)

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.

Background: This study was performed to establish age-related serum reference intervals for procollagen type I N-propeptide (P1NP) and type I collagen C-telopeptide (CTx) in the Australian population., Methods: Fasting sera from 1143 males (mean age 60 years; range 20-97 years) and 1246 females (mean age 53 years; range 20-93 years) who participated in the Geelong Osteoporosis Study were analysed for CTx and P1NP using the automated Roche Modular Analytics E170 analyser., Results: Optimal age-related reference intervals were based on the central 90% of the distribution. The male CTx reference interval was divided into three age groups. For men aged 25 to 40 years, the interval was 170-600 ng/L; 40 to 60 years, the interval was 130-600 ng/L; and for men aged greater 60 years the interval was 100-600 ng/L. For P1NP the male reference interval was 15-80 μg/L for men aged between 25 to 70 years. In men greater than 70 years of age values were higher possibly due to increased bone turnover. High values are frequently seen for both CTx and P1NP in males aged younger than 25 years. This is probably due to bone growth that is not completely finalised. The female CTx reference interval was divided into four age groups. For women aged less than 30 years, the interval was 150-800 ng/L; 30-39 years, the interval was 100-700 ng/L; 40-49 years, the interval was 100-600 ng/L; and for women aged 50 years or more the interval was 100-700 ng/L. The female P1NP reference interval was divided into four age groups. For women aged less than 30 years, the interval was 25-90 μg/L; 30-39 years, the interval was 15-80 μg/L; 40-49 years, the interval was 15-60 μg/L; and for women aged 50-69 years the interval was 15-75 μg/L. In women greater than 70 years of age values were higher possibly due to increased bone turnover., Conclusion: Values obtained from this large study provide sound age-related reference intervals for serum P1NP and CTx values in the Australian population., (Copyright © 2013 Elsevier Inc. All rights reserved.)

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.

Background: Whereas several epidemiological studies suggest that low dietary intake of vitamins C and E is linked to increased hip fracture in smokers and antioxidants (dietary and endogenous) are reduced in elderly osteoporotic women, none has demonstrated an effect of supplemental antioxidants on bone turnover., Methods: In an observational study of 533 randomly selected women, we investigated the associations among the use of antioxidant supplements, vitamins C and E, serum levels of biochemical markers of bone turnover (C-telopeptide [CTx] and bone-specific alkaline phosphatase [BSAP]), and whole body bone mineral density (BMD)., Results: Twenty-two women were identified as current users of supplemental vitamin C or E. Duration of antioxidant supplement use was negatively associated with age-adjusted and weight-adjusted serum CTx, such that mean CTx levels (natural log transformed) were 0.022 units lower for each year of exposure. No significant differences were detected for adjusted serum BSAP or whole body BMD., Conclusions: Our results suggest that antioxidant vitamin E or C supplements may suppress bone resorption in nonsmoking postmenopausal women. Coupling of bone formation and resorption may explain the absence of an effect on bone formation markers, given evidence of enhanced effects of antioxidants on osteoblast differentiation; this warrants further investigation. This work adds to the growing body of evidence that antioxidants may play a role in preventing osteoporosis.

Background: Laboratory services for the support of heart and lung transplantation in Australia have adapted to the special needs of the clinicians looking after the heart and lung transplantation patients., Methods: Pre-transplantation standardized tests encompassing a wide variety of different parameters are carried out both to establish the suitability of patients for a transplant and to maximize the chance of success following this procedure. Potential solid organ recipients routinely have blood samples sent to a number of centers Australia-wide so that human leukocyte antigen (HLA) presensitization can be checked for at the time a donor becomes available in any state in Australia. Although prospective HLA matching is not performed for thoracic organ transplant recipients, pre-existing antibodies to donor HLA antigens are a contra-indication to transplantation. Following transplantation, the predominant roles of the laboratory are in the monitoring of immunosuppressive drug levels, in the detection of allograft rejection, and in the detection of bacterial infection or viral reactivation. While a number of markers have been proposed in the detection of rejection, we currently rely on interpretation of the histological analysis of biopsies. The treatment with immune suppressive agents, in particular cyclosporin A, has made organ transplantation from non-HLA identical donors possible. As cyclosporin A and other immune suppressive drugs have significant side effects, their concentrations need to be carefully followed to guarantee sufficient immune suppression while avoiding renal failure and other complications including excessive immunosuppression and infectious disease risk. Recently, the role of viral reactivation with the human cytomegalovirus (HCMV) has attained more prominence. HCMV is a potential pathogen in up to 90% of thoracic organ transplant recipients and in the pre-gancyclovir era, it was a major cause of morbidity and mortality in at-risk lung transplant recipients. New PCR-based assays that measure the viral load levels of HCMV allow earlier intervention and more appropriate treatment strategies to prevent the HCMV disease syndromes and optimize the HCMV prophylaxis strategy., Conclusions: Diagnostic pathology testing to support heart and lung transplantation is a combination of routine testing and specialized testing. Depending on the time-critical nature of the tests, this testing has to be done on site or in more centralized testing facilities. Further developments in the laboratory support of heart and lung transplantation will hopefully continue to improve both the short- and long-term outcomes of thoracic organ transplant recipients.