Abstract Background On standard dosing of infliximab (IFX), one third of patients will develop secondary loss of response (LOR) by the first year and up to 50% of initial responders will develop LOR by 5 years.1 Sustained high trough levels and dose escalation are proven to increase the durability of infliximab.2 The role of proactive therapeutic drug monitoring (TDM) to guide this remains controversial. In 2019, our unit opted for proactive TDM (at week 6, week 14 and 6 monthly thereafter) as standard therapy to guide dose escalation in maintenance. We report the outcomes of our patient cohort over 2 years from initiation of IFX. Methods A retrospective chart review was performed between 01/01/2019 to 31/12/2021. All patients with IBD who received IFX were included. Patients with acute severe colitis were excluded as treatment protocol was different. Data on demographics, disease characteristics, immunomodifier, IFX dosing, frequency, drug and antibody levels were collected and analysed. Primary outcome was switching to different biologic as a marker of treatment failure. Standard IFX dosing is 5mg/kg IVI at 0, 2, 6 weeks for induction and 8 weekly in maintenance. The dose was escalated if week 6<15µg/mL, week 14/maintenance <5µg/mL, or <10µg/mL in stricturing/fistulising disease. Results 98 patients (58% male) were identified, 82% had Crohn’s disease (CD) and 18% Ulcerative Colitis (UC). Median age at diagnosis was 11 years old, and 12.5 years old at starting IFX. 81% received an immune modifier of which 64% had methotrexate and 39% azathioprine. 13% received escalated induction and 77% received escalated maintenance. The median week 6 level of standard vs escalated maintenance group was 22.8µg/mL vs 12.4µg/mL (p=0.01). 3% did not respond to induction and were discontinued. 2% developed IFX antibodies. At 1 year, 5% of CD and 22% of UC patients switched to a different biologic and at 2 years this was 13% and 44% respectively. Median time to switch was 53 weeks. Switching to alternate biologic was associated with escalated induction OR 5.2 (p<0.01) UC phenotype OR 5.6 (p<0.01) and concomitant steroid use OR 5.2 (p<0.04). Conclusion Our week 6 IFX level guided clinician decision to escalate dosing in maintenance. The outcomes for our cohort show good treatment durability particularly in CD, 95% at 1 year and 87% at 2 years, which is better than what has been reported.2 Patients with severe phenotype remain poor responders and difficult to treat as evident by receiving escalated induction, i.e escalation without TDM, and steroid use being predictors. This study adds to the growing body of evidence of the role of proactive TDM in increasing durability of IFX. References 1.Ding, N. S., Hart, A., & De Cruz, P. (2016). Systematic review: predicting and optimising response to anti-TNF therapy in Crohn's disease - algorithm for practical management. Alimentary pharmacology & therapeutics, 43(1), 30–51. https://doi.org/10.1111/apt.13445 2.Vahabnezhad, E., Rabizadeh, S., & Dubinsky, M. C. (2014). A 10-year, single tertiary care center experience on the durability of infliximab in pediatric inflammatory bowel disease. Inflammatory bowel diseases, 20(4), 606–613. https://doi.org/10.1097/MIB.0000000000000003

Abstract Background Mental health issues such as anxiety and depression in patients with inflammatory bowel disease (IBD) are well-documented in the literature1,2. Aim: We reviewed the cohort within our new IBD psychology service, to establish the prevalence of anxiety and depression in the Australian paediatric setting. Methods 213 outpatients aged 5-18 attending the outpatient IBD service at the Children’s Hospital at Westmead, Australia were recruited from April to October 2024. They completed a validated self-report tool, PROMIS Paediatric Profile v2.0 – Profile 25, which measures anxiety, depression, mobility, fatigue, peer relationships, pain interference, and pain intensity. Clinical disease data, including PUCAI/PCDAI scores and biochemical markers (faecal calprotectin, ESR, and CRP) were collected for the same visits. Demographic data included age, sex, disease type (Crohn’s Disease or Ulcerative Colitis), and age at diagnosis. Results Moderate to severe levels of anxiety, depression, and fatigue were reported by 28.7%, 20.2%, and 26.7% of participants, respectively. There was a significant difference in psychological distress (combined anxiety and depression) across different groups when stratified on age of diagnosis (i.e. ages 0-5, 6-12, and 13-18; F(2, 208)=5.37, p=.005). Psychological distress positively correlated with clinical disease severity (PCDAI: r=.244, p=.007; PUCAI: r=.317, p=.004), and pain interference (r=.600, p<.001) and intensity (r=.461, p<.001); negatively correlated with mobility (r=-.514, p<.001) and peer relationships (r=-.437, p<.001). A hierarchical regression was conducted to assess predictors of psychological distress among participants. Fatigue emerged as the strongest predictor in the final model, significantly explaining additional variance in distress levels (F(1, 164)=79.34, p<.001). Additionally, mobility and sex also emerged as significant predictors of psychological distress (ps=.049 and .017, respectively), while age, biochemical markers, and disease severity were non-significant. This model explained 57.3% of the variance in psychological distress. Conclusion Paediatric patients with IBD experience significant burden from anxiety, depression, and fatigue. The strong association between fatigue and psychological distress mirrors findings in the adult IBD population3, suggesting that fatigue and psychological factors significantly influence each other, independent of the disease state. These results underscore the importance of targeted screening and management of psychological symptoms to improve IBD care and improve quality of life in paediatric patients. References 1.Butwicka A, Olén O, Larsson H, et al. Association of childhood-onset inflammatory bowel disease with risk of psychiatric disorders and suicide attempt. JAMA Pediatr. 2019 Oct;173(10):969-978. doi: 10.1001/jamapediatrics.2019.2662. 2.Cooney R, Tang D, Barrett K, Russell RK. Children and young adults with inflammatory bowel disease have an increased incidence and risk of developing mental health conditions: a UK population-based cohort study. Inflamm Bowel Dis. 2024 Aug;30(8):1264-1273. doi: 10.1093/ibd/izad169. 3.Uhlir V, Stallmach A, Grunert PC. Fatigue in patients with inflammatory bowel disease-strongly influenced by depression and not identifiable through laboratory testing: a cross-sectional survey study. BMC Gastroenterol. 2023 Aug 22;23(1):288. doi: 10.1186/s12876-023-02906-0. PMID: 37608313; PMCID: PMC10463723.

Introduction: Central venous catheter (CVC) complications are frequent in children with intestinal failure (IF) on home parenteral nutrition (HPN). The aims of the study were to evaluate complications and main causes for catheter loss in these patients. Methods: Single-centre retrospective review of CVC-related complications in children discharged on HPN from 2000 to 2020. Data collected included patient demographics, type of CVC, line complications and patients outcomes. From 2015 patients on HPN were routinely started on taurolidine-citrate catheter lock solution as central line-associated bloodstream infection (CLABSI) prophylaxis. Results: Thirty-six children were included. Main IF causes were short bowel syndrome (n=18), dysmotility (n=11) and enteropathies (n=5). Most patients were started on parenteral nutrition at <1 year of age (55.6%). A total of 172 CVCs were used (median 4 lines/patient, IQR 2-6): 116 (67.4%) tunnelled CVCs, 37 (21.5%) peripherally inserted central catheters (PICCs), 17 (9.9%) non-tunnelled CVCs and 2 (1.2%) port-a-caths. There were 189 catheter-related complications (4.14 events/1000 line days); 168 of them involved tunnelled CVCs and are described in Table 1. Most CLABSI were caused by gram-negative (46.7%) and gram-positive bacteria (26.7%). CLABSI rate was 2.65/1000 line days before use of taurolidine-citrate catheter locks, and 0.35/1000 line days after its routine use (20,709 and 22,762 line days, respectively). Salvage of tunnelled CVCs after complication occurred in 92 (56%) occasions. Main reasons for line removal were infection (35%) and malposition (32.5%). Median life of tunnelled CVCs was 255 days (IQR 84.5-524.2). Thirty (83.3%) children are alive and 17 (56.7%) achieved enteral autonomy, one after isolated intestinal transplant. Thirteen (43.3%) patients continue on HPN with median time on HPN of 68.5 months (IQR 50.5-92.5). Conclusion: The use of taurolidine-citrate locks in HPN paediatric patients has reduced the number of CLABSIs. Prevention of CVC-related complications is essential for long-term survival of these patients.TABLE 1.: Tunnelled CVCs complications in children with IF on HPN.

BACKGROUND:Aspirin may reduce the risk of vascular graft thrombosis after cardiovascular surgery. We previously reported the 30-day results of a trial evaluating aspirin use before coronary artery surgery. Here we report the 1-year outcomes evaluating late thrombotic events and disability-free survival. METHODS:Using a factorial design, we randomly assigned patients undergoing coronary artery surgery to receive aspirin or placebo and tranexamic acid or placebo. The results of the aspirin comparison are reported here. The primary 1-year outcome was death or severe disability, the latter defined as living with a modified Katz activities of daily living score < 8. Secondary outcomes included a composite of myocardial infarction, stroke and death from any cause through to 1 year after surgery. RESULTS:Patients were randomly assigned to aspirin (1059 patients) or placebo (1068 patients). The rate of death or severe disability was 4.1% in the aspirin group and 3.5% in the placebo group (relative risk, 1.17; 95% confidence interval, 0.76-1.81; P = .48). There was no significant difference in the rates of myocardial infarction (P = .11), stroke (P = .086), or death (P = .24), or a composite of these cardiovascular end points (P = .68). With the exception of those with a low European System for Cardiac Operative Risk Evaluation score (P = .03), there were no interaction effects on these outcomes with tranexamic acid (all tests of interaction P > .10). CONCLUSIONS:In patients undergoing coronary artery surgery, preoperative aspirin did not reduce death or severe disability, or thrombotic events through to 1 year after surgery.

Background. In a post hoc analysis of the ENIGMA-II trial, we sought to determine whether intraoperative dexamethasone was associated with adverse safety outcomes.Methods. Inverse probability weighting with estimated propensity scores was used to determine the association of dexamethasone administration with postoperative infection, quality of recovery, and adverse safety outcomes for 5499 of the 7112 non-cardiac surgery subjects enrolled in ENIGMA-II.Results. Dexamethasone was administered to 2178 (40%) of the 5499 subjects included in this analysis and was not associated with wound infection [189 (8.7%) vs 275 (8.3%); propensity score-adjusted relative risk (RR) 1.10; 95% confidence interval (CI) 0.89-1.34; P = 0.38], severe postoperative nausea and vomiting on day 1 [242 (7.3%) vs 189 (8.7%); propensity scoreadjusted RR 1.06; 95% CI 0.86-1.30; P = 0.59], quality of recovery score [ median 14, interquartile range (IQR) 12-15, vs median 14, IQR 12-16, P = 0.10), length of stay in the postanaesthesia care unit [ propensity score-adjusted median (IQR) 2.0 (1.3, 2.9) vs 1.9 (1.3, 3.1), P = 0.60], or the primary outcome of the main trial. Dexamethasone administration was associated with a decrease in fever on days 1-3 [ 182 (8.4%) vs 488 (14.7%); RR 0.61; 95% CI 0.5-0.74; P<0.001] and shorter lengths of stay in hospital [ propensity score-adjusted median ( IQR) 5.0 ( 2.9, 8.2) vs 5.3 ( 3.1, 9.1), P<0.001]. Neither diabetes mellitus nor surgical wound contamination status altered these outcomes.Conclusion. Dexamethasone administration to high-risk non-cardiac surgical patients did not increase the risk of postoperative wound infection or other adverse events up to day 30, and appears to be safe in patients either with or without diabetes mellitus.Clinical trial registration. NCT00430989.

It is important to detect and treat hypovolaemia; however, detection is particularly challenging in the conscious, spontaneously breathing patient. Eight healthy male volunteers were monitored using four minimally invasive monitors: Vigileo FloTrac; LiDCOrapid; USCOM 1A; and CardioQ oesophageal Doppler. Monitor output and clinical signs were recorded during incremental venesection of 2.5% estimated blood volume aliquots to a total of 20% blood volume removed. A statistically significant difference from baseline stroke volume was detected after 2.5% blood loss using the LiDCO (p=0.007), 7.5% blood loss using the USCOM (p=0.019), and 12.5% blood loss using the CardioQ (p=0.046) and the FloTrac (p=0.028). Receiver operator characteristic curves for predicting >10% blood loss had areas under the curve of 0.68-0.82. The minimally invasive cardiac output devices tested can detect blood loss by a reduction in stroke volume in awake volunteers, and may have a role in guiding fluid replacement in conscious patients with suspected hypovolaemia.

It is important to detect and treat hypovolaemia; however, detection is particularly challenging in the conscious, spontaneously breathing patient. Eight healthy male volunteers were monitored using four minimally invasive monitors: Vigileo FloTrac(™) ; LiDCOrapid(™) ; USCOM 1A; and CardioQ(™) oesophageal Doppler. Monitor output and clinical signs were recorded during incremental venesection of 2.5% estimated blood volume aliquots to a total of 20% blood volume removed. A statistically significant difference from baseline stroke volume was detected after 2.5% blood loss using the LiDCO (p = 0.007), 7.5% blood loss using the USCOM (p = 0.019), and 12.5% blood loss using the CardioQ (p = 0.046) and the FloTrac (p = 0.028). Receiver operator characteristic curves for predicting > 10% blood loss had areas under the curve of 0.68-0.82. The minimally invasive cardiac output devices tested can detect blood loss by a reduction in stroke volume in awake volunteers, and may have a role in guiding fluid replacement in conscious patients with suspected hypovolaemia.

1Learn about the various types of paediatric liver transplant2Identify the early and late complications of paediatric liver transplantation3Describe the role of interventional radiological techniques in identification and treatment of vascular and nonvascular short- and long-term complications after transplantation. Liver transplantation is the definitive treatment for paediatric end-stage liver disease. Postoperative complications may result in graft failure and poor patient survival. Improved IR techniques are now available that help in recognition of vascular and nonvascular complications of liver transplantation and their timely treatment resulting in improved graft and patient survival. Types of paediatric liver transplants and the surgical techniques are briefly illustrated. Various IR techniques (such as catheter drainage, angioplasty (+/- stenting), parenchymal biopsy) used in the diagnosis and treatment of the following complications after liver transplantation are described with the help of illustrative examlpes: 1Vascular: a) Hepatic artery thrombosis, b) Hepatic artery stenosis, c) Portal vein thrombosis, d) Portal venous stenosis, d) Hepatic venous outflow tract obstruction (HVOTO), e) Hepatic artery pseudoneurysm2Nonvascular: AParenchymal: Acute/chronic rejectionBBiliary: a) Bile leak/biloma formation b) Intrahepatic and anastomotic biliary stricturesCPostoperative fluid collections and abscess 1Transplantation is the definitive treatment for paediatric end stage liver disease.2Vascular and nonvascular complications can occur early or late and may lead to graft failure after liver transplantation.3Interventional radiology techniques aid identification of, and timely and minimally invasive treatment of both early and late complications after transplantation, thus improving graft and patient survival.

We retrospectively audited the incidence of blood transfusion and related this to preoperative haemoglobin levels in 181 patients undergoing lower limb arthroplasty over a six-month period. This included 102 primary total knee replacements, 52 primary total hip replacements, 11 revision total knee replacements and 16 revision total hip replacements. The overall incidence of transfusion was 16.0%. The incidence in primary arthroplasty was 11% (9.8% for total knee replacements and 13.5% for total hip replacements), and in revision surgery was 44.4% (27.3% for total knee replacements and 56.3% for total hip replacements). Combining data for primary total knee replacements and primary total hip replacements, a preoperative haemoglobin threshold of 120 g/l divided patients into high and low risk groups for transfusion. Below or equal to this threshold the incidence of transfusion was 47.7%; above this threshold the incidence was 7.2%. We suggest that patients having primary lower limb arthroplasty with a preoperative haemoglobin of 120 g/l or less should undergo investigation of their anaemia and optimisation of erythropoeisis.

Anaesthesia in Australia is amongst the safest in the world. This record of safety is under threat from increasing pressures to operate at times of poor human performance, particularly late at night. Our institution has a policy mandating the prioritisation of surgery based on clinical need while minimising the risks associated with after-hours surgery. The policy states that "only Category 1 (urgent, needing immediate surgery) and Category 2 cases which cannot wait until the morning should be done between 2230 and 0800". From 5 March 2007 we performed an eight-week prospective audit of all cases where surgery occurred in this time period. The anaesthetic senior registrar on duty recorded the clinical priority of the case. There were 95 cases commenced between 2230 and 0800 hours during the audit period, of which 28 (30%) were in clear breach of this policy, in some cases delaying urgent surgery. The potential implications of such breaches are significant in the context of worse outcomes for patients undergoing surgery in the after-hours period. When non-urgent cases occupy resources, the capacity of the system to deal with the truly urgent case is significantly impaired. Adequate 'in-hours' resourcing, capacity and appropriate scheduling may be key to maintaining the excellent safety record of anaesthesia. A large study prospectively examining morbidity, error and outcomes of after-hours operating would serve to further elucidate the risk benefit ratio of after-hours operating.

O'Loughlin, E; Stormon, M; Shun, A; Verran, D; Crawford, M; Resurruccion, L; Jermyn, V; Wong, C; Lord, D Author Information