The where, who and how of adrenal vein sampling in Australia and New Zealand.

INTRODUCTION: Primary aldosteronism (PA) causes 10-15% of cases of hypertension, and it is increasingly recognised as being under-diagnosed. An interventional radiology procedure, adrenal vein sampling (AVS), is a necessary and important diagnostic procedure for complete workup of PA. There is an anticipated increase in demand for AVS as detection of PA improves. This study aims to describe the current landscape of AVS in Australia and New Zealand (NZ). METHODS: Two surveys exploring AVS methodology and performance were conducted of (i) Endocrinology Unit Heads and (ii) interventional radiologists who perform AVS, at public hospitals with Endocrinology Units across Australia and NZ. RESULTS: Responses were received from 48/53 Endocrinology Unit Heads (91%) and 35 radiologists from 26 sites (87% of AVS sites). AVS was provided at 28/48 Endocrinology sites (58%) across Australia and NZ. In Australia, sites were concentrated in Victoria, New South Wales and Queensland with none in the Northern Territory; in NZ, sites were more evenly distributed across the North and South Islands. AVS was performed by 1-2 dedicated radiologists at 24 sites, 2-3 radiologists at two sites and a rotating roster of radiologists at two sites. Responses to both surveys revealed significant variation in AVS methodology and interpretation of AVS results. CONCLUSION: There is significant heterogeneity in the availability of AVS, the procedural details and the interpretation of results across Australia and NZ, which potentially impacts the quality of patient care and ability to scale up AVS capacity to meet increasing demand.

The potential use of folate and its derivatives in treating psychiatric disorders: A systematic review.

OBJECTIVES: To examine the strengths and limitations of existing data to provide guidance for the use of folate supplements as treatment, with or without other psychotropic medications, in various psychiatric disorders. To identify area for further research in terms of the biosynthesis of mechanism of folate and genetic variants in metabolic pathway in human. METHODS: A systematic review of published literature following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, to assess whether folate supplements are beneficial in certain psychiatric disorders (depression, bipolar disorder, schizophrenia, autism spectrum disorder, and attention deficit hyperactivity disorder). Methodology of this review is registered with Prospero (Registration number CRD 42021266605). DATA SOURCES: Eligible studies were identified using a systematic search of four electronic databases: Embase, Pubmed, PsycINFO, and Cochrane. The search strategy covered the time period from 1974 to August 16th, 2021. Therefore, this review examines randomized control trials or open-label trials completed during this period. RESULTS: We identified 23 studies of folate supplements in various psychiatric disorders for critical review. Of these, 9 studies investigated the efficacy of folate supplements in major depressive disorders, 5 studies in schizophrenia, 6 studies in autism spectrum disorder, 2 studies in bipolar affective disorder and 1 study in attention deficit hyperactive disorder. The most consistent finding association of oral levomefolic acid or 5-methylfolate with improvement in clinical outcomes in mental health conditions as mentioned above, especially in major depressive disorder (including postpartum and post-menopausal depression), schizophrenia, autism spectrum disorder, attention deficit hyperactivity disorder and bipolar affective disorder. Folate supplements were well tolerated. LIMITATION: Our results are not representative of all types of studies such as case reports or case series studies, nor are they representative of the studies conducted in languages that are not in English or not translated in English. CONCLUSION: Increasing evidence from clinical trials consistently demonstrate folate supplements, especially levomefolic acid or 5-methylfolate, may improve clinical outcomes for certain psychiatric diseases, especially as an adjunct pharmacotherapy with minimal side effects.

Comparison of the efficacy of tea tree (Melaleuca alternifolia) oil with other current pharmacological management in human demodicosis: A Systematic Review.

Various treatments are found to be moderately effective in managing Demodex-related diseases except tea tree oil (TTO) and terpinen-4-ol (T4O), which showed superior miticidal and anti-inflammatory effects in numerous clinical studies. Their possible effects include lowering mite counts, relieving Demodex-related symptoms, and modulating the immune system. This review summarizes the current clinical topical and oral treatments in human demodicosis, their possible mechanisms of action, side-effects and resistance in treating this condition. TTO (especially T4O) is found to be the most effective followed by metronidazole, ivermectin and permethrin in managing the disease. This is because TTO has anti-parasitic, anti-bacterial, anti-fungal, anti-inflammatory and wound-healing effects. Furthermore, nanoTTO can even release its contents into fungus and Pseudomonas biofilms. Combinations of different treatments are occasionally needed for refractory cases, especially for individuals with underlying genetic predisposal or are immuno-compromised. Although the current treatments show efficacy in controlling the Demodex mite population and the related symptoms, further research needs to be focused on the efficacy and drug delivery technology in order to develop alternative treatments with better side-effects profiles, less toxicity, lower risk of resistance and are more cost-effective.

Remnant cholesterol and coronary atherosclerotic plaque burden assessed by computed tomography coronary angiography.

BACKGROUND AND AIMS: There remains a substantial residual risk of ischaemic heart disease (IHD) despite optimal low-density lipoprotein cholesterol (LDLC) reduction. Part of this risk may be attributable to remnant cholesterol, which is carried in triglyceride-rich lipoproteins. We evaluated the relationship between remnant cholesterol and coronary atherosclerotic plaque burden assessed non-invasively by computed tomography coronary angiography (CTCA) in patients with suspected coronary artery disease (CAD). METHODS AND RESULTS: This was a multicentre study of 587 patients who had a CTCA and fasting lipid profile within 3 months. Calculated remnant cholesterol was total cholesterol minus LDLC minus high-density lipoprotein cholesterol (HDLC). Significant coronary atherosclerotic burden was defined as CT-Leaman score >5 (CT-LeSc), an established predictor of cardiac events. Mean age was 61 ±â€¯12 years and mean pretest probability of CAD was 23.2 ±â€¯19.8%. LDLC levels were <1.8 mmol/L in 134 patients (23%), of whom 82% were statin-treated. Patients with CT-LeSc >5 had higher mean remnant cholesterol than those with CT-LeSc ≤5 (0.76 ±â€¯0.36 mmol/L vs. 0.58 ±â€¯0.33 mmol/L, p = 0.01). On univariable analysis, remnant cholesterol (p = 0.01), LDLC (p = 0.002) and HDLC (p < 0.001) levels predicted CT-LeSc >5, whilst triglycerides (p = 0.79) had no association with CT-LeSc >5. On multivariable analysis in the subset of patients with optimal LDLC levels, remnant cholesterol levels remained predictive of CT-LeSc >5 (OR 3.87, 95% confidence interval 1.34-7.55, p = 0.004), adjusted for HDLC and traditional risk factors. CONCLUSIONS: Remnant cholesterol levels are associated with significant coronary atherosclerotic burden as assessed by CTCA, even in patients with optimal LDLC levels. Future studies examining whether lowering of remnant cholesterol can reduce residual IHD risk are warranted.

Use of deferasirox (Exjade) for iron overload in peritoneal dialysis patients.

A 54 year old male with b-Thalassemia major developed ESRD and was managed with continuous ambulatory peritoneal dialysis. Although not able to be transfused due to high titre red cell antibodies he did require management of iron overload. Deferasirox (Exjade) was administered orally. There was concern that excretion of iron via the peritoneal dialysate may raise the risk of iron-dependent infections (Yersinia and Rhizopus).Whilst receiving Exjade 1000mg /day, a total collection of 12.7L of peritoneal dialysate was collected over a 24 hour period by the patient. The dialysate total iron levels were measured by ICP-MS at 0.46mmol/L which equates to 0.33mg of Fe in total. Over a 6 month period his serum ferritin fell from 3869µg/l to 1545µg/l. There were no episodes of peritonitis. Since only 7-8% of the deferasirox and iron complex is excreted through the urine, the amount of Fe seen in the patient's dialysate might be expected to be up to 1.5-1.6mg. Yet, the results of the Fe levels in the patient's PD fluid was a meagre 0.33mg, about five times lower than expected.Whilst only moderately effective at a dosage of 1000mg/day, deferasirox may be a safe agent for iron removal in iron overloaded peritoneal dialysis patients, as relatively low dialysate iron levels reduces the risk of Yersinia and Rhizopus infection.

Can the tea tree oil (Australian native plant: Melaleuca alternifolia Cheel) be an alternative treatment for human demodicosis on skin?

Australian tea tree oil (TTO) and its extract terpinen-4-ol (T4O) are found to be effective in moderating demodex-related diseases. Their possible effects are lowering the mite counts, relieving the demodex-related symptoms and modulating the immune system especially the inflammatory response. This review summarizes the topical treatments of TTO and T4O in human demodicosis, their possible mechanism of actions, side-effects and potential resistance in treating this condition. Although current treatments other than TTO and T4O are relatively effective in controlling the demodex mite population and the related symptoms, more research on the efficacy and drug delivery technology is needed in order to assess its potential as an alternative treatment with minimal side-effect profile, low toxicity and low risk of demodex resistance.

Vitamin D in newborns. A randomised controlled trial comparing daily and single oral bolus vitamin D in infants.

AIM: There are no published data to demonstrate the efficacy of bolus dose vitamin D in newborn infants. The study sought to evaluate this alternative approach of supplementation. METHODS: This single centre, open randomised controlled trial was conducted from August 2013 to May 2014. It compared the efficacy and safety of daily (400 IU) versus a bolus dose (50 000 IU) of cholecalciferol in newborn infants of vitamin D deficient mothers. The primary outcome measure was the rate of 25 hydroxyvitamin D (25OHD) repletion-defined as 25OHD greater than 50 nmol/L. The secondary objective was determining safety using adjusted total serum calcium. RESULTS: Of 70 eligible infants, 36 received a daily dose and 34 received a single high-dose cholecalciferol. Mean 25OHD in the bolus group (154 nmol/L, 95% confidence interval (CI) 131-177) was higher than the daily group (48 nmol/L, 95% CI 42-54) at 1-2 weeks of age. This was reversed at 3-4 months, (65 nmol/L, 95% CI 59-71) compared with the daily group (81 nmol/L, 95% CI 77-85). More infants in the single bolus group achieved vitamin D repletion (100 vs. 31%) at 1-2 weeks. By 3-4 months, both groups achieved similar vitamin D repletion rates (91 vs. 89%). Mean adjusted total serum calcium in the bolus group were normal at 1-2 weeks (2.73 mmol/L) and 3-4 months (2.55 mmol/L). CONCLUSION: Single bolus dosing of 50 000 IU cholecalciferol achieves higher 25OHD repletion rates at 1-2 weeks of age compared with daily dosing, but repletion rates were similar by 3-4 months. There was no hypercalcaemia documented with single bolus dosing in this study.

Harmonisation of Osmolal Gap - Can We Use a Common Formula?

Osmolal gap is the difference between the measured osmolality and a calculated osmolality based on the major commonly measured osmotically active particles. The perceived gap indicates the presence of unmeasured osmotically active particles. The major use of osmolal gap today is to screen for the possible presence of exogenous toxic substances in patients in an emergency department or intensive care unit. There is a long history of osmolal gap calculations and it needs to be appreciated that the uncertainty of the osmolal gap will be determined by the sum of errors in the calculated osmolality, error in measured osmolality and variability in unmeasured analytes. Since 1958 there has been a constant trickle of papers proposing both simple and sophisticated formulae to calculate the 'ultimate' osmolal gap. A gap as close to zero as possible and with a low coefficient of variation across multiple clinical conditions and analytical platforms are also determinants of 'fitness for purpose' of any osmolal gap calculations. The Smithline-Gardner formula for calculated osmolality [2(Na) + Glu + Urea] is fit for purpose in both normal people and general hospital patients. It also performs well across different analytical platforms. This simple formula can be used for rapid mental calculation at the bedside and automated laboratory information system reporting whenever a measured osmolality is requested. In this era of harmonisation, we propose that this formula be adopted by all clinicians and laboratories.

Calculated Chemistry Parameters - do they need to be harmonised?

In clinical chemistry, harmonisation of the testing process is a global initiative with the purpose of improving patient safety, allowing better integration of research data and enabling the use of national electronic heath records. In Australia, as in other countries, the initial focus has been on the harmonisation of the more commonly measured analytes. There are also a number of calculated parameters, derived from these measured analytes, which could also be considered for harmonisation. Calculated parameters that are reported by laboratories and used for clinical decision-making should undergo the same robust process of harmonisation as is the case for the measured analytes. Aspects that should be considered for harmonisation are: terminology, the formulae used and where possible the use of common reference intervals. To investigate pathways towards the harmonisation of calculated parameters, three commonly reported parameters are considered. Calculated osmolality, the anion gap and albumin-adjusted calcium are all derived from common analytes which have individually been considered for harmonisation. They present different methodological, measurement uncertainty and terminological hurdles to harmonisation and are likely to require different pathways and solutions.

Thalassemia bone disease: a 19-year longitudinal analysis.

Thalassemia is an inherited disorder of alpha or beta globin chain synthesis leading to ineffective erythropoiesis requiring chronic transfusion therapy in its most severe form. This leads to iron overload, marrow expansion, and hormonal complications, which are implicated in bone deformity and loss of bone mineral density (BMD). In this 19-year retrospective longitudinal study, the relationships between BMD (determined by dual-energy X-ray absorptiometry) and risk factors for osteoporosis in 277 subjects with transfusion-dependent thalassemia were examined. The mean age at first review was 23.2 ± 11.9 years and 43.7% were male. Hypogonadism was present in 28.9%. Fractures were confirmed in 11.6% of subjects and were more frequent in males (16.5%) compared with females (7.7%). Lumbar spine (LS), femoral neck (FN), and total body (TB) Z-scores were derived. Patients with transfusion-dependent thalassemia had a significant longitudinal decline in BMD at the FN and TB. In the linear mixed-model analysis of BMD and risk factors for bone loss, FN Z-score was more significantly associated with risk factors compared with the LS and TB. The rate of decline at the FN was 0.02 Z-score per year and was 3.85-fold greater in males. The decline in FN Z-score over the last 5 years (years 15 to 19) was 2.5-fold that of the previous 7 years (years 8 to 14) and coincided with a change in iron chelator therapy from desferrioxamine to deferasirox. Hemoglobin (Hb) levels positively correlated with higher TB and LS Z-scores. In conclusion, the FN is the preferred site for follow-up of BMD. Male patients with ß-thalassemia experienced a greater loss of BMD and had a higher prevalence of fractures compared with females. Transfusing patients (particularly males) to a higher Hb target may reduce the decline in BMD. Whether deferasirox is implicated in bone loss warrants further study.

Effect of exercise on albuminuria in people with diabetes.

AIM: Spot urine measurement of albumin is now the most commonly accepted approach to screening for proteinuria. Exertion prior to the collection may potentially influence the result of spot urine albumin estimation. We aim to evaluate the effect of exercise on albuminuria in subjects at various stages of diabetic nephropathy in comparison with healthy control volunteers. METHODS: Thirty-five people with diabetes (19 with normoalbuminuria (NA), nine with microalbuminuria (MA) and seven with overt proteinuria (OP)) and nine control subjects were assessed. A 1 km treadmill walk was performed. Four spot urine specimens were collected: first morning void, immediately prior to exercise, and 1 h and 2 h after exercise. A random effects linear regression mixed model was used to assess the effect of exercise on albumin/creatinine ratio (uACR). Results are presented separately for male and female subjects with diabetes due to a significant exercise/gender interaction (P < 0.05). RESULTS: No significant effect of exercise on uACR was seen in control subjects. In NA males with diabetes no effect of exercise was seen, while in females uACR 1 h after exercise was significantly higher than the early morning sample (3.55 mg/mmol (96% confidence interval 0.27-6.83). Both female and male diabetes subjects with MA have increase in uACR 1 h after exercise (87.8, -24.3-199.4 and 6.7, 2.1-11.3). For both males and females with OP, uACR was significantly increased 1 h post exercise (67.5, 22-113 and 21.6, 8.4-34.8, respectively). In all groups uACR at 2 h after exercise was not significantly different to the early morning sample. CONCLUSIONS: Exercise increased uACR estimation in normoalbuminuric subjects with diabetes with a larger effect in females. Whether exercise unmasks early diabetic nephropathy in NA subjects requires further study.