Australasia Paediatric Endocrine Group

Sustainable strategies are urgently required to rehabilitate sulfidic waste rocks (W R ) and prevent acid and metalliferous drainage (AMD) into natural environments. This study aims to establish the proof of concept for transforming aluminosilicate-rich acidic mine wastes into a stable, consolidated, and cementitious structure (namely environmental geopolymer ) using alkali activation of W R and Class F fly ash (FA) at ambient temperature. The synthesised mineral gel effectively cemented W R -FA mixtures (up to 60 % W R ) into indurated structures. A mechanical strength of approximately 22 MPa was developed in 4 weeks, strengthening further to 29 MPa over 24 weeks. Mineralogical, geochemical, and micro-spectroscopic analysis revealed that acidic minerals in the W R materials were encapsulated and passivated by the cement-like amorphous sodium aluminosilicate hydrate (N-A-S-H) gel phase, which significantly immobilised toxic metal(loid)s. Further investigation into atomic coordination environment of the synthetic gel using Near-edge X-ray absorption fine structure (NEXAFS) at Si and Al K-edge suggested that tetrahedrally coordinated Si and Al form the 3D-extended network structure within the amorphous gel phase. This chemically activated cementation of polymineral wastes may offer a unique approach to valorise sulfidic W R and FA into a pseudo-sedimentary rock horizon for sustainable rehabilitation of sulfidic W R facilities through a combined mechanism of physical integration, as well as mineralogical and geochemical stabilisation. • Alkali activation transforms waste rock and fly ash into an indurated geopolymer. • The hardened geopolymer achieves ∼ 22 MPa strength after 4 weeks of ambient curing. • N-A-S-H gel encapsulated and passivated pyrite, preventing AMD generation. • Tetrahedral Si and Al polycondensation forms the 3D geopolymer network structure. • Polymineral gels immobilise the toxic metal(oid)s in the geopolymer samples.

Virtual clinical care is a rapidly developing component of modern health systems. As Andrew Staib and Stephen Gourley say in an editorial, the ability to provide specialist decision making, advice and monitoring where it might otherwise not be available is a major advantage of virtual emergency care. Remote and pre-hospital retrieval environments are areas where the virtual presence of specialist emergency physicians have shown particular benefits. They wisely caution that these new models need robust evaluation when assessing efficacy and cost-effectiveness. Linked to the editorial is a fascinating paper from a large team in Victoria. They conducted a return-on-investment analysis of a virtual ED (VED) program developed in response to local changing healthcare needs, using an economic model based on initial patient outcome data to assess the healthcare costs, potential costs saved and return-on investment from the VED. Every day in EDs, clinicians face situations where they need to decide whether to detain a patient for assessment and treatment. For patients who meet the relevant criteria, provisions of mental health legislation can be used. For other patients, clinicians often rely on so-called ‘duty of care’. In an excellent review, the authors explore this complex area of law, including the relevant legislation, common law principles and grey areas. Highly recommended reading. We publish a survey that sought to identify barriers to recognising and reporting potential child abuse by medical officers and nursing staff in the EDs of three Western Sydney hospitals. The authors conclude that a combination of hospital, departmental and individual staff issues such as time limitations, lack of resources, education and support are barriers to reporting suspected child abuse. In the first large-scale study since the 1980s to explore external causes of unintentional childhood injury presenting to Australian paediatric EDs, six major paediatric hospitals in four Australian states provided data for 2011–2017 on age, gender, attendance time/date, presenting problem, injury diagnosis, triage category and mode of separation. Three hospitals supplied data on external cause and intent of injury. A total of 486 762 ED presentations for unintentional injury in children aged 0–14 were analysed. The results supplement existing knowledge of hospitalised paediatric injury to better understand the causes of childhood injury by age and gender, which require health service utilisation. Opioid-related harm has risen in recent decades, but there is limited research to describe the clinical burden of opioid poisoning to Australian EDs. We publish an observational series of prospectively collected data investigating presentations of opioid poisoning to an ED in Newcastle, NSW (1990–2021). Type of opioid, naloxone administration, intubation, intensive care unit admission, length of stay and death were extracted from the unit's database. Opioid presentations increased in number and severity over three decades as the type of opioid changed. Oxycodone is currently the main opioid of concern. Methadone poisoning was the most severe. Between June 2016 and June 2020, 1548 major trauma patients were admitted to Christchurch Hospital or died in the ED. An analysis of these case concludes that after controlling for age and injury severity, having a lower temperature on arrival in ED was a significant modifiable risk factor for death. Additionally, intubation prior to hospital, increased base deficit, lower initial haemoglobin and lower GCS were risk factors associated with death. The authors suggest that all pre-hospital services should have key performance indicators for temperature measurement and management. A team from Western Australia report the demographic profile of adult patients presenting with constipation and constipation-related issues to an Australian Tertiary Hospital ED, the first study to investigate the management of constipation in adult patients in an Australian ED setting. They conclude that it is important that ED clinicians recognise that functional constipation is a chronic condition and many patients have persistent symptoms. There are opportunities for quality-of-care improvements including diagnostics, treatment, and referral post-discharge to allied health, nursing and medical specialist services. The subject covered in this issue is volunteering, a component of personal and professional life for many clinicians, and one that is rarely discussed openly.

Fasciolosis is an endemic zoonotic parasitic disease with significant impacts on human health and both animal health and production. Early post-infection impacts on the host remain unclear. The objective of this study was to determine the changes, if any, to levels of endotoxin in cattle plasma in response to early-stage infection with Fasciola hepatica. Thirty-six (36) commercial bred cattle were experimentally infected with approximately 400 viable metacercariae. Plasma lipopolysaccharide (endotoxin) levels were examined on 24 occasions from 0 h before infection to 336 h after infection using the Limulus Amoebocyte Lysate chromogenic end point assay and compared with that of six (6) uninfected control animals. Peak lipopolysaccharide levels in infected animals were reached at 52 h after infection and returned to pre-infection levels at time 144 h after infection. Infected animals had significantly elevated lipopolysaccharide levels between 24 and 120 h after infection when compared to uninfected animals. The mean change in endotoxin units (EU)/mL over time after infection was statistically significant in infected animals. Elevations of lipopolysaccharide occurred in all infected animals suggesting a possible repeatable and titratable endotoxemia conducive to therapeutic agent model development.

BackgroundThe sheep blowfly, Lucila cuprina, is a myiasis‐causing parasite responsible for significant production losses and welfare issues for the Australian sheep industry. Control relies largely on the use of insecticides. The pyrimidine compound, dicyclanil, is the predominant control chemical, although other insecticides also are used, including imidacloprid, ivermectin, cyromazine and spinosad. We investigated in vitro resistance patterns and mechanisms in field‐collected blowfly strains.ResultsThe Walgett 2019 strain showed significant levels of resistance to both dicyclanil and imidacloprid, with resistance factors at the IC50 of 26‐ and 17‐fold, respectively, in in vitro bioassays. Co‐treatment with the cytochrome P450 inhibitor, aminobenzotriazole, resulted in significant levels of synergism for dicyclanil and imidacloprid (synergism ratios of 7.2‐ and 6.1‐fold, respectively), implicating cytochrome P450 in resistance to both insecticides. Cyp12d1 transcription levels were increased up to 40‐fold throughout the larval life stages in the resistant strain compared to a reference susceptible strain, whereas transcription levels of some other cyp genes (6g1, 4d1, 28d1) did not differ between the strains. Similar resistance levels also were observed in flies collected from the same property in two subsequent years.ConclusionThis study indicates that in vitro resistance to both dicyclanil and imidacloprid in this field‐collected blowfly strain is likely mediated by cytochrome P450, with Cyp12d1 implicated as the enzyme responsible; however, it remains possible that another P450 also may be involved. A common resistance mechanism for the two drugs has important implications for drug rotation strategies designed to prolong the useful life of flystrike control chemicals. © 2022 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

518 Background: Body Mass Index (BMI) impacts breast cancer risk and prognosis. Conflicting results have been published regarding BMI as a predictive factor for endocrine therapy benefit. CDK4/6 inhibitors (CDK4/6i) in combination with endocrine treatment (ET) are standard-of-care treatments for metastatic hormone receptor-positive breast cancer. In contrast to cytotoxic chemotherapy, CDK4/6i are given at a fixed dose irrespective of BMI or weight. The PALLAS trial compared the combination of the CDK4/6i palbociclib and adjuvant ET to ET alone in the early breast cancer setting. This analysis investigates the impact of BMI on the efficacy and the side effect profile of palbociclib (P) in the PALLAS trial. Methods: In this pre-planned analysis, patients (pts) enrolled in PALLAS were categorized according to BMI as underweight (BMI <18.5 kg/m2), normal weight (BMI 18.5-24.9 kg/m2), overweight (BMI 25-29.9 kg/m2) and obese (³30 kg/m2), respectively. Adverse event differences were assessed with Chi-squared tests. Time to early discontinuation of P was analyzed with Fine and Gray competing risk models. Cox models were used to investigate the association between BMI category and time to invasive disease-free survival (iDFS). Results: Of a total of 5698 pts included in this analysis, 68 (1.2%) were underweight, 2082 (36.5%) normal weight, 1818 (31.9%) overweight and 1730 (30.4%) obese at baseline. Significantly different rates of all grade neutropenia were observed in normal weight, overweight and obese pts with regard to total (88.5%, 85.7% and 74.7%), as well as grade 3 (64.1%, 62.0% and 43.9%) and grade 4 neutropenia (7.0%, 3.6% and 2.0%), respectively. The lower frequency and severity of neutropenia observed in overweight and obese pts was associated with a significant lower treatment discontinuation rate over time when compared to normal weight patients (overweight vs normal weight: HR 0.73 CI 0.63-0.84, p<0.0001, and obese vs normal weight: HR 0.65 CI 0.56-0.75, p<0.0001). In pts treated with P, neutropenia was the primary toxicity leading to treatment discontinuation in 21.1% of normal weight pts, 14.0% of overweight pts and 5.9% obese pts, respectively. Despite these observations, there was no statistically significant improvement in iDFS with the addition of P to ET in any weight category (normal weight HR 0.84 CI 0.63-1.12, overweight HR 1.10 CI 0.82-1.49 and obese HR 0.95 CI 0.69-1.30). Conclusions: This pre-planned analysis of outcomes by BMI in the PALLAS trial demonstrates significantly less frequent and less severe neutropenia in overweight and obese pts compared to those with normal weight, leading to significant lower treatment discontinuation rates. However, no difference in iDFS outcomes by BMI was observed. Additional long-term follow-up will further evaluate whether BMI ultimately impacts outcome. Clinical trial information: NCT02513394.

Precision (personalised) medicine for non-small cell lung cancer (NSCLC) adopts a molecularly guided approach. Standard-of-care testing in Australia is via sequential single-gene testing which is inefficient and leads to tissue exhaustion. The purpose of this study was to understand preferences around genetic and genomic testing in locally advanced or metastatic NSCLC. A discrete choice experiment (DCE) was conducted in patients with NSCLC (n = 45) and physicians (n = 44). Attributes for the DCE were developed based on qualitative interviews, literature reviews and expert opinion. DCE data were modelled using a mixed multinomial logit model (MMNL). The results showed that the most important attribute for patients and clinicians was the likelihood of an actionable test, followed by the cost. Patients significantly preferred tests with a possibility for reporting on germline findings over those without (β = 0.4626) and those that required no further procedures over tests that required re-biopsy (β = 0.5523). Physician preferences were similar (β = 0.2758 and β = 0.857, respectively). Overall, there was a strong preference for genomic tests that have attribute profiles reflective of comprehensive genomic profiling (CGP) and whole exome sequencing (WES)/whole genome sequencing (WGS), irrespective of high costs. Participants preferred tests that provided actionable outcomes, were affordable, timely, and negated the need for additional biopsy.

Objective To externally validate the “2021 AAGL Endometriosis Classification” staging system. Design Retrospective, diagnostic accuracy study Setting Multicentre Population or Sample Two hundred and seventy-two endometriosis patients (January 2016 - October 2021) Methods Three independent observers analysed coded surgical data to assign an AAGL surgical stage (1 to 4) as the index test, and surgical complexity level (A to D) as the reference standard. Main Outcome Measures The diagnostic accuracy of each AAGL stage to predict corresponding AAGL surgical complexity level was determined. Receiver operating characteristic curves used to determine the accuracy of cut off points used in the AAGL staging system to discriminate between surgical complexity levels. Results 272 cases were analysed. Diagnostic accuracy (sensitivity, specificity, PPV and NPV) for three observers were: stage 1 to predict level A 97.9-98.7%, 60.2-64.2%, 75.0-76.9%, and 96.3-97.5%; stage 2 to predict level B 26.1-30.4%, 93.2-95.6%, 26.3-35.3%, and 92.9-93.6%; stage 3 to predict level C 7.5-10.0%, 93.8-94.8%, 33.3-42.1%, and 70.9-71.5%; stage 4 to predict level D 90.-95.0%, 90.1-91.7% &, 41.9-47.5%, and 99.1-99.6%. For three observers AUROC for A vs B/C/D (cut-point 9) 0.75-0.88, A/B vs C/D (cut-point 16) 0.81 and A/B/C vs D (cut-point 22) 0.95-0.96. Conclusions This external validation study demonstrates that the AAGL Endometriosis Classification performs poorly overall for the prediction of surgical complexity. The results from this external validation study suggest that the system in its current form is not generalizable to all endometriosis patients and should be reviewed before its universal implementation. Funding Nil Keywords Endometriosis, staging, laparoscopy

We recently published a comprehensive qualitative literature review of time-based targets and their impact on emergency care. In this issue we publish another comprehensive literature review, this time from the quantitative perspective. Quality of care generally improved after targets were introduced and when compliance with targets was high. This depended on how targets were implemented at individual sites or within jurisdictions, with important implications for policy makers, health managers and clinicians. We will be publishing a final paper in this series of three, together with an editorial and a letter to the editor, in the next issue. A retrospective analysis of demand and occupancy data provided by ACEM accredited EDs in voluntary surveys at the start of June and September 2017–2020 looks at the impact of the COVID-19 pandemic. Hospitals answering all surveys were grouped and compared by jurisdiction and role delineation. ED occupancy increased by more than demand between 2017 and 2019, with some decrease in 2020: in June 2020 presentations were 12.7% lower than 2019 and in September 2020 back to the normal range outside Victorian and major paediatric hospitals. Future research needs to consider locality, role delineation and work practice change in comparing ED pandemic responses. How accurate and safe is the Canadian Syncope Risk Score (CSRS) for patients presenting with syncope. A single centre prospective observational study in Brisbane, of adults presenting to ED with syncope, reported that the CSRS did not miss any clinically relevant outcomes in low risk patients, making it potentially useful in aiding their disposition. Larger validation studies in Australia are encouraged to test the diagnostic accuracy of the CSRS. Health care workers in Pacific Island Countries face unique workload and infection control hazards because of limited resources, cultural practices and local disease burden. In the context of COVID-19, concern around health care worker safety escalated in the region. The Health Worker Safety Guide for COVID-19 is a relevant and usable protocol developed using local knowledge and now available in several Pacific languages. The authors recommended a creative approach to facilitate meaningful communication with these clinicians, including low resolution technology and use of social media platforms. We publish a multi-centre observational study of patients presenting with out-of-hospital cardiac arrest to one of five tertiary care hospital EDs in Hanoi from 2017 to 2019. Out of 239 cases 70.7% were witnessed and 8.4% received bystander CPR. Emergency medical services transported 20.5% of cases to hospital with the remainder transported by private vehicle. No patients received external defibrillation before arriving to hospital. Return of spontaneous circulation in hospital was 33.1%, 3.8% patients survived to hospital discharge and only one patient was discharged with a favourable neurological outcome. Urgent investments in pre-hospital capacity, training and capabilities, will improve outcomes for out-of-hospital cardiac arrest in Hanoi. Does ear acupuncture, using a modified Battlefield technique as an adjunct to standard analgesia care (SAC), significantly reduce pain scores compared with sham acupuncture or SAC alone? A research team from Australia and Hong Kong report inconclusive results. In a medical emergency, the usual requirement to obtain consent before giving treatment does not apply. This is known as the ‘emergency principle’. Although the fundamentals of the principle are uncontroversial, there are some uncertainties and inconsistencies in this law in relation to certain parameters. The authors suggest the law should be clarified. This issue the focus is on the challenge of managing people who are frequent attenders (also known as frequent presenters and frequent flyers) to our EDs.

Internationally, Indigenous and minoritised ethnic groups experience longer wait times, differential pain management and less evaluation and treatment for acute conditions within emergency medicine care. Examining Emergency Department Inequities (EEDI) investigates whether inequities between Māori and non-Māori exist within EDs in Aotearoa New Zealand (NZ). A team from Auckland present the descriptive findings for their study. Using secondary data from ED admissions into 18/20 District Health Boards in NZ between 2006 and 2012, there were a total of 5 972 102 ED events (1 168 944 Māori, 4 803 158 non-Māori). The researchers found an increasing proportion of ED events per year, with a higher proportion of Māori from younger age groups and areas of high deprivation compared to non-Māori events. Māori also had a higher proportion of self-referral and were to be seen within a longer timeframe compared to non-Māori. There are different patterns of ED usage when comparing Māori and non-Māori events. The next level of analysis of the EEDI dataset will be to examine whether there are any associations between ethnicity and ED outcomes for Māori and non-Māori patients. Kim Yates, also from Auckland, offers her perspective in an accompanying editorial. ECPR is a promising adjunct to routine advanced cardiac life support. Growing worldwide interest in ECPR-use has seen more tertiary centres offering ECPR programmes. A team from Auckland City Hospital report on the extracorporeal membranous oxygenation service provided there. Despite the potential benefits of ECPR, it is currently only offered on an ad hoc basis. It remains unknown whether the hospital will manage sufficient numbers of patients to warrant an ECPR programme. An accompanying editorial concludes that ‘establishing an ECPR programme is resource intensive and requires robust procedures and integration among various stakeholders, including hospital administration, local ambulance services, emergency physicians, critical care specialists, cardiology/cardiac surgery and nursing and multidisciplinary care providers’. Intubation of children in the emergency setting is a high-risk, low incidence event. Standardisation of clinical practice has been hampered by a lack of high-quality evidence to support one technique over another. In a voluntary questionnaire undertaken by medical staff at registrar level or above in EDs and ICU associated with the Paediatric Research in Emergency Departments International Collaborative and Australian and New Zealand Intensive Care Society Paediatric Study Group, respondents reported on their individual intubation practices, with a focus on pre-oxygenation and apnoeic oxygenation techniques, and the use of video laryngoscopy. The conclusion is that within Australia and NZ, there is considerable variation in paediatric emergency airway clinical practice, in particular with respect to pre-oxygenation, apnoeic oxygenation and use of video laryngoscopy. Definitive clinical trials are required to best inform clinical practice in this. Despite ultrasound-guided peripheral intravenous catheter insertion being a well-established method for patients with difficult intravenous access, currently there are limited hospital-based training programmes. A team from the Gold Coast University Hospital describe the training programme they established in their hospital and health service over 5 years ago and how it can be replicated in other centres. NOF fractures are common and serious injuries in the elderly persons. When a NOF fracture is suspected but is not clearly visible on radiographs, guidelines recommend magnetic resonance imaging (MRI), or computed tomography (CT) if MRI is not available/contraindicated. A team of radiologists from Austin Health in Melbourne reviewed the use of CT and subsequent MRI for suspected NOF fractures in patients with negative or equivocal radiographs. They conclude that access to CT for evaluation of suspected occult NOF fractures is much quicker compared to MRI. When CT results are negative with ongoing clinical suspicion of an occult fracture, MRI should be performed in a time-efficient manner. We publish several papers about this deadly virus, including one from Hong Kong that examines the impact it had on ED attendances there in 6 months and one that reports an innovative way to hold routine departmental mortality and morbidity meetings. This section of the journal has a new team of editors. After several years of consistently excellent, reliable and professional work, Colin Banks and Jeremy Furyk are hanging up their FOJ pens. Thank you both. I'm delighted to welcome the new team of Sierra Beck, Bridget Honan, James Mallows and Joseph Ting. Decision fatigue in the ED is the focus in this issue, something we can all relate to.