John Hunter Hospital

Background Drug–drug interaction (DDI) alerts target the co-prescription of two potentially interacting medications and are a frequent feature of electronic medical records (EMRs). There have been few controlled studies evaluating the effectiveness of DDI alerts. This study aimed to determine the impact of DDI alerts on rates of DDIs and on associated patient harms. Methods Quasi-experimental controlled pre–post study in five Australian hospitals. Three hospitals acted as control hospitals (EMR with no DDI alerts) and two as intervention (EMR with DDI alerts). Only DDI alerts at the highest severity level (defined as ‘major contraindicated’) were switched on at intervention hospitals. These alerts were not tailored to clinical context (ie, patient, drug). A total of 2078 patients were randomly selected from all patients (adult and paediatric) admitted to hospitals 6 months before and 6 months after EMR implementation. A retrospective chart review was performed by study pharmacists. The primary outcome was the proportion of admissions with a clinically relevant DDI. Secondary outcomes included the proportions of admissions with a potential DDI and with DDI-related harm. Results Potential DDIs were identified in the majority of admissions (n=1574, 74.7%) and clinically relevant DDIs identified in half (n=1026, 48.7%). DDI alerts were associated with a reduction in the proportion of admissions with potential DDIs (adjusted OR (AOR)=0.38 (0.19, 0.78)) but no change in clinically relevant DDIs (AOR=1.12 (0.68, 1.84)) or in DDI-related harm (AOR=2.42 (0.47,12.31)). 199 DDIs (76 at control and 123 at intervention hospitals) for 35 patient admissions were associated with patient harm, and 2 patients experienced severe DDI-related harm pre-EMR implementation. Discussion Implementation of DDI alerts, without tailoring alerts to clinical context, is unlikely to reduce patient harms from DDIs. Organisations should reconsider implementation of DDI alerts in EMRs where significant tailoring of alerts is not possible. Future research should focus on identifying safe, efficient and cost-effective ways of refining DDI alerts, so expected clinical benefits are achieved, and negative consequences of excessive alerting are minimised.

Background Overseas birth is associated with a survival advantage in colorectal cancer in Australia. We wished to analyse this survival based on global region of birth, controlling for cancer-specific and other causes of death. Methods A database of resected colorectal cancers from 2010 to 2016 (n = 1596) was grouped according to patient global region of birth. Chi-squared testing was used to compare factors including patient demographics and AJCC stage. Kaplan–Meier and competing-risk analysis were used to compare 5-year survival outcomes between patients born in different regions, and regression analysis was used to control for age. Results 751 (47.1%) patients were born overseas. 385 (24.1%) originated from Europe, 124 (7.8%) from East and SE Asia, 92 (5.8%) from the Middle East, and the remainder from other global regions. Immigrants from East or SE Asia were more likely to present with node-positive disease (p = 0.048) than those born in Australia. Immigrants from East and SE Asia and the Middle East had significantly better all-cause 5-year survival than patients born in Australia (73.4% and 80.4% vs. 60.4%, p < 0.0001). Immigrants from the Middle East retained their cancer-specific survival advantage after competing risk analysis (HR 0.76, p = 0.027). Immigrants from Europe displayed no significant difference in all-cause or disease-specific survival compared to individuals born in Australia. Conclusion Patients born in the Middle East appear to have a colorectal cancer-specific survival advantage compared to those born in Australia, unrelated to stage at presentation. This has significant implications for prognosis and future research directions.

Background Pilon fractures are historically associated with suboptimal outcomes. No long‐term Australian data is available on patient‐reported outcomes. We hypothesised that pilon fracture long‐term outcomes are inferior to Australian population norms. Methods A 14‐year retrospective study was conducted in a Level‐1 trauma centre on AO/OTA type‐B/C fractures. Type‐A fractures, skeletally immature, interpreter requirement and primary amputation were excluded. Demographics, injury characteristics, management and complications were collected. The primary outcome was SF‐36 with adjusted Australian norms. Results From 127 eligible patients, 73 were included in the study (age: 46 ± 17 years; 50 [69%] males) with 8.7 ± 3.9 years follow‐up. Management included ORIF 46 (61%), external fixation (EF) with staged ORIF 17 (23%), definitive EF 4 (5%) and 8 (11%) non‐operative. Further surgical intervention was required in 25 (34%) patients, with the majority for hardware removal (14 [19%]). Compared with Australian SF‐36 norms, the mean Physical Component Score was lower (44.7 ± 8.9 vs. 50.3, p ≤ 0.001) whereas the Mental Component Score (51.2 ± 12.5 vs. 51.2, p = 0.24) was not. Median return to work was 4.5 months (IQR 5), with 47 (87%) of the 54 employed pre‐injury working at 12 months. Two (3.7%) patients did not return to work and 24 (44%) returned at a reduced capacity. Conclusion This study provides a contemporary reference for pilon fractures managed in Australia. Outcomes were favourable when compared internationally. These patients are likely to resume employment, often at reduced capacity, while experiencing moderate long‐term impacts to their physical well‐being due to persistent pain.

Kava plant root ( piper methysticum ) is an ingredient used in ceremonial drinks throughout Pacific and South Sea Island communities. Kava is made up of kavalactones; psychoactive compounds that act as central nervous system depressants. The rare occurrence of kavalactone toxicity manifests most commonly with hepatotoxicity, and cases of myoglobinuria have been reported. Our case describes an association of significant kava tea ingestion with acute tubulo‐interstitial nephritis. An 18‐year‐old male, without any medical comorbidities, presented with oliguric acute kidney injury after ingesting 15 cups of kava tea. His creatinine at admission was 223umolL and peaked at 96 h post ingestion at 970umol/L despite intravenous fluid administration. His urine ACR was 196 mg/mmol, with microscopic haematuria; a creatinine kinase was 780 U/L, C3 was mildly reduced (0.77 g/L) with normal C4, and the remainder of a glomerulonephritis screen was negative. He did not have any evidence of hepatotoxicity but was bradycardic with a prolonged QT interval. A urine drug screen was negative for other substances. A kidney biopsy demonstrated severe acute tubulointerstitial nephritis without acute tubular necrosis or evidence of myoglobulin‐related injury. He was commenced on oral corticosteroids and had complete recovery of his kidney function after 2 weeks, without requiring kidney replacement therapy. Toxicology analysis of the kava powder identified four different kavalactones without additional substances.

Traumatic injuries are a leading cause of global morbidity and mortality, with 40 million people permanently injured and nearly 6 million deaths every year. Approximately 90% of trauma-related deaths occur in low- and middle-income countries, and 50% of trauma-related deaths are believed to be preventable. Although effective trauma systems encompassing prehospital, hospital, and rehabilitative care are critical for improving outcomes, global documentation remains limited. This study provides a comparative analysis of trauma care systems across 8 countries—the United States, Canada, Brazil, Belgium, the Netherlands, Australia, Japan, and South Africa—spanning 5 continents. Each country's analysis includes demographic context, system organization (including prehospital, hospital, and posthospital care), clinical and systemic outcomes, and future directions. Trauma systems across countries vary significantly in the structure and regulation of trauma care, injury patterns, national data collection, and accessibility, reflecting diverse demographics and healthcare infrastructures. National trauma registries are well established in countries like the Netherlands, Japan, and Canada but are in early development stages in Brazil, South Africa, and Belgium. In some countries, such as the Netherlands and Canada, trauma from traffic collisions and falls dominates, whereas others, such as Brazil and South Africa, have higher rates of violence-related injuries like homicides. Accessibility in remote areas remains a challenge in countries with large landmasses such as Canada and Australia, where rural populations often face limited or delayed trauma care. Other countries, such as the United States and South Africa, face different challenges linked to disparities in quality of and access to care between public and private systems. Although centralization of trauma care, standardization of national trauma care systems, and investment in workforce and infrastructure are universal goals for improving outcomes, solutions tailored to each country are required to optimize trauma systems globally.

This study aimed to compare computational fluid dynamics (CFD) results to those acquired in vivo with 4D Flow magnetic resonance imaging (MRI) and in vitro with a 3D printed model using pressure catheter manometry. The goal was to investigate the haemodynamics of the cerebral venous system (CVS) and assess the accuracy of the methodologies, to highlight any discrepancies between the techniques. One participant living with multiple sclerosis (MS) and one healthy control were recruited for this study. MRI was performed to generate 3D geometries of the anatomy and to compute blood flow rates at the boundaries, with 4D Flow MRI velocity streamlines for the control participant. CFD models were created for the two participants and simulated using the patient-specific boundary conditions. A 3D printed geometry of the MS participant was created and a flow loop experiment was conducted to measure the cerebral venous pressures. The venous pressures were found to be comparable to that observed in the CFD simulation. 4D Flow MRI velocity streamlines of the CVS were found to correspond well to the CFD findings, except for a few regions, which were likely impacted by the low resolution of the MRI. The use of all three methods enabled the successful validation of the velocity, flow features and pressure, and ensured that the haemodynamics of the CVS as resolved using CFD, were accurate. This highlights the potential for increased efficacy of the clinical outcomes of future studies that utilise such methods. Graphical abstract

Background Current guidelines recommend routine fasting before cardiac catheterization under conscious sedation. However, data supporting this practice have been limited. Aims We aimed to compare the safety and patient well‐being of a non‐fasting strategy to standard fasting in patients who undergo heart catheterization procedures. Methods We conducted a meta‐analysis of randomized studies comparing fasting versus non‐fasting before cardiac catheterization. We systematically reviewed PubMed, Embase, and Cochrane databases until October 2024. We incorporated unpublished subgroup data from the previously published SCOFF Trial, exclusively on patients who underwent catheterization procedures. Results We included 7 RCTs comprising 3289 patients who underwent cardiac catheterization procedures. The pooled analysis demonstrated the non‐inferiority of the non‐fasting strategy, with no significant differences in the incidences of nausea/vomiting (RR 0.90; 95% CI 0.50−1.61; p = 0.72), hypoglycemia (RR 0.78; 95% CI 0.45−1.35, p = 0.38), acute kidney injury (RR 1.45; 95% CI 0.77−2.75, p = 0.251), and length of hospital stay (SMD 0.005, 95% CI −0.109 to 0.099, p = 0.92) compared to the fasting strategy. The non‐fasting strategy was significantly associated with reduced rates of intraprocedural hypotension and showed a statistically significant improvement in overall patient satisfaction (SMD −0.749; 95% CI −1.26; −0.234, p = 0.004) when compared to the fasting strategy. Conclusion A non‐fasting strategy before cardiac catheterization procedures is as safe as the standard fasting protocol and demonstrates a significant improvement of overall patient satisfaction. These findings support the consideration of non‐fasting protocols as a patient‐centered approach that maintains safety while enhancing the patient experience.

Aboriginal people have a high risk of type 2 diabetes (T2DM). Routine opportunistic testing using glycated hemoglobin (HbA1c) for diabetes in the emergency department (ED) offers an opportunity to detect undiagnosed diabetes and evaluate glycaemia for pre-existing diabetes. To evaluate the prevalence of pre-existing diabetes and assess random blood glucose (RBG) and HbA1c as screening tools for undiagnosed diabetes in Aboriginal people attending the ED. Demographic and RBG data were extracted for all Aboriginal adults presenting to a Sydney hospital ED over 6 months. Practitioners requested blood tests as per routine care, and in the final 3 months, HbA1c was automatically added to routine venous sampling. The primary outcome was change in diabetes diagnosis with the addition of HbA1c. Overall, 1640 adult Aboriginal patients presented to the ED over 6 months (4.1% of all presentations), including 734 unique individuals tested during routine care. The prevalence of pre-existing T2DM was 12.0% (n = 88). Among those without known diabetes, 1.4% (n = 9) had glucose readings ≥11.1 mmol/L and 14.3% (n = 90) had glucose readings 7.0–11.0 mmol/L. For those without known diabetes with HbA1c measurement, there were 2.7% (n = 8) with HbA1c ≥6.5% and 4% (n = 12) with HbA1c 6.0%–6.4%. There was no overlap between those who had an HbA1c ≥6.5% and RBG ≥11.1 mmol/L. There was a high prevalence of pre-existing diabetes among Aboriginal adults attending the ED. New diabetes diagnosis in the ED based on RBG or HbA1c was not common. Confirmatory testing for diabetes should be recommended to the general practitioners of patients in whom elevated HbA1c or RBG are identified.

The methodological approaches used to evaluate the inhibitory effects (potency determination) of tocolytic agents on human uterine contractions in ex vivo systems vary, and none of the methodologies has been subjected to scrutiny in terms of objectivity, variability, and reliability. Therefore, this study aimed to assess and compare the reliability of using area under the curve (AUC) versus amplitude alone-based assessment of contraction traces to generate concentration-response curves, which were then used to calculate the tocolytic concentrations that inhibited 25% (IC 25 ) and 50% (IC 50 ) of baseline contractility. The accuracy of the determined inhibitory concentrations (IC) was then scrutinized while taking into consideration the contraction parameters (amplitude, frequency, duration) affected by the different tocolytics. To do this, pregnant human myometrial strips (term, not-in-labor) were treated with cumulative concentrations of the contraction-blocking agents, nifedipine (NIF), indomethacin (IND), 2-aminoethoxydiphenyl borate (2-APB), glycyl-h-1152 (GH), aminophylline (AMP), or rolipram (ROL)). Concentration-response curves were generated using either AUC or amplitude alone as the index of contraction inhibition, from which tocolytic IC 25 and IC 50 concentrations were calculated and compared (i.e. IC 25(AUC) vs. IC 25(Amplitude) ). The effects of each tocolytic on contraction frequency were also quantified. To assess accuracy, each tocolytic was applied to contracting strips as a single treatment at their respective IC 25(AUC/Amplitude) and IC 50(AUC/Amplitude) , and then the inhibitory effect re-quantified against both contraction AUC and amplitude alone. Significant differences between IC 50(AUC) and IC 50(Amplitude) were detected for AMP (318.5 vs. 450 µM), ROL (4.3 vs. 55 µM), and IND (59.5 vs. 75 µM), whereas AUC versus amplitude-based IC 50 concentrations were comparable for NIF (10 vs. 10 nM), GH (18.2 vs. 15 µM), and 2-APB (53 vs. 57 µM). Similarly, the determined IC 25(AUC) and IC 25(Amplitude) were again significantly different for AMP (175 vs. 277 µM), ROL (515 nM vs. 15 µM), and IND (28 vs. 42 µM), but also for 2-APB (27 vs. 40 µM). The confirmation studies revealed that a single dose of the tocolytics at their determined IC 25(AUC) and IC 50(AUC) concentrations consistently reduced contraction AUC by approximately 25% and 50%, respectively, whereas single doses of the IC 25(Amplitude) and IC 50(Amplitude) concentrations revealed inconsistent results. Of the six tocolytics, four reduced contraction amplitude by > 25% when applied as a single dose at IC 25(Amplitude) , while three reduced contraction amplitude by > 50% when applied at IC 50(Amplitude) . Our experimental data indicate that when determining tocolytic potency, assessment of ex vivo contraction traces via AUC is more accurate and consistent than assessment via amplitude alone. Our study finds that whilst tocolytics that increase contraction frequency (while decreasing amplitude) can be assessed by either AUC or amplitude-based determination, tocolytics that either significantly reduce or largely do not affect contraction frequency should only be analyzed via AUC.

Early detection of feeding difficulties in childhood is critical for timely support, which may prevent simple feeding problems from becoming pervasive or resistant to intervention. Our study aimed to describe the range of the knowledge, attitudes and practices of established paediatricians, GPs, CHNs and early childcare educators working with young children with feeding difficulties and their caregivers. Focus groups and semi-structured interviews were conducted with Australian paediatricians, General Practitioners (GPs), Child Health Nurses (CHNs), and early childhood educators working with children aged two years and below. Findings from our study suggest that healthcare practitioners are relying on anthropometric measurements of growth to identify feeding difficulties, and the most common age at which feeding difficulties are seen in practice is after two years of age. Food insecurity, cultural factors, and access to specialised services are still a challenge, creating a barrier to early identification and intervention.

The term ‘nephrotoxin’ is often imprecisely applied to medications that are not inherently toxic to the kidneys, including renin‐angiotensin‐aldosterone system inhibitors, sodium‐glucose co‐transporter 2 inhibitors, diuretics and metformin. These drugs are frequently included in ‘sick day rules’ and may be prematurely discontinued during acute illness or acute kidney injury (AKI). However, these medications offer substantial benefits, such as preserving cardiac and kidney function and reducing mortality. Discontinuing them without appropriate clinical judgement can lead to unintended harm. Clinicians should adopt a patient‐specific, evidence‐based approach when managing medications in AKI and chronic kidney disease, informed by pharmacology and individualised risk assessment. Patients may overinterpret advice to ‘stop nephrotoxic medications’ as a permanent measure, leading to hesitation in restarting necessary treatments. This misconception can create barriers to optimal care and complicate decision‐making, as patients may prioritise avoiding perceived harm over addressing their full medical needs. This manuscript emphasises the need for nuanced and informed decision‐making in the management of medications in kidney‐related conditions.

We report the case of a 38‐year‐old Caucasian man with well‐controlled HIV on antiretroviral therapy who developed nephrotic syndrome. The patient presented with a maculopapular rash, lymphadenopathy, oral lesions, nasal congestion and bilateral pitting oedema. Laboratory tests revealed hypoalbuminemia, nephrotic range proteinuria and abnormal liver function. Further investigations confirmed secondary syphilis with positive Treponema pallidum serology. Kidney biopsy showed membranous nephropathy. Treatment with Benzathine benzylpenicillin resulted in a rapid resolution of nephrotic syndrome, improved liver function and normalisation of serum albumin levels. This case highlights the rare but recognised link between syphilis and nephrotic syndrome, emphasising the importance of prompt diagnosis and antibiotic treatment to prevent the need for more aggressive treatments. Syphilis can cause a variety of systemic manifestations, and co‐infection with HIV is common due to their shared transmission route. Healthcare providers must remain vigilant in considering syphilis as a potential cause of nephrotic syndrome in HIV‐positive patients, particularly when other clinical and laboratory features suggest its presence.

Objective To describe patients' perspectives and experiences of medications for gout to inform patient-centred practice. Methods Systematic review (MEDLINE, Embase, PsychInfo, CINAHL) and thematic analysis of studies using qualitative methodology to May 2023. Results Five dominant themes were identified in 45 studies involving 1203 patients:- denying illness, negotiating uncertainty, juggling competing priorities, avoiding suffering and lifestyle restrictions, and developing strategies and empowerment. Conclusion Patients with gout wanted to avoid suffering and lifestyle restrictions but were concerned with stigmatisation and had uncertainty about medications. Comprehensive information about the disease and reframing the role of the different medications is needed to overcome the barriers to adherence to available and effective treatment. Our results highlight the fundamental importance of maintaining a patient-centred focus and include some avenues of how clinicians may redefine their approach to gout management.