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Background: Severe cutaneous adverse reactions (SCAR) are a group of delayed presumed T-cell mediated hypersensitivities associated with significant morbidity and mortality. Despite their shared global healthcare burden and impact, the clinical phenotypes, genomic predisposition, drug causality, and treatment outcomes may vary. We describe the establishment and results from the first Australasian registry for SCAR (AUS-SCAR), that via a collaborative network advances strategies for the prevention, diagnosis and treatment of SCAR., Methods: Prospective multi-center registry of SCAR in Australian adult and adolescents, with planned regional expansion. The registry collects externally verified phenotypic data drug causality, therapeutics and long-term patient outcomes. In addition, biorepository specimens and DNA are collected at participating sites., Results: we report on the first 100 patients enrolled in the AUS-SCAR database. DRESS (50%) is the most predominant phenotype followed by SJS/TEN (39%) and AGEP (10%), with median age of 52 years old (IQR 37.5, 66) with 1:1 male-to-female ratio. The median latency for all implicated drugs is highly variable but similar for DRESS (median 15 days IQR 5,25) and SJS/TEN (median 21 days, IQR 7,27), while lowest for AGEP (median 2.5 days, IQR 1,8). Antibiotics (54.5%) are more commonly listed as primary implicated drug compare with non-antibiotics agent (45.5%). Mortality rate at 90 days was highest in SJS/TEN at 23.1%, followed by DRESS (4%) and AGEP (0%)., Conclusion: In the first prospective national phenotypic and biorepository of SCAR in the southern hemisphere we demonstrate notable differences to other reported registries; including DRESS-predominant phenotype, varied antibiotic causality and low overall mortality rate. This study also highlights the lack of standardised preventative pharmacogenomic measures and in vitro / in vivo diagnostic strategies to ascertain drug causality., Trial Registration: ANZCTR ACTRN12619000241134. Registered 19 February 2019., Competing Interests: No relevant conflicts of interest to declare., (© 2024 The Author(s).)

Background: Burn inhalation injury (BII) is a major cause of burn-related mortality and morbidity. Despite published practice guidelines, no consensus exists for the best strategies regarding diagnosis and management of BII. A modified DELPHI study using the RAND/UCLA (University of California, Los Angeles) Appropriateness Method (RAM) systematically analysed the opinions of an expert panel. Expert opinion was combined with available evidence to determine what constitutes appropriate and inappropriate judgement in the diagnosis and management of BII., Methods: A 15-person multidisciplinary panel comprised anaesthetists, intensivists and plastic surgeons involved in the clinical management of major burn patients adopted a modified Delphi approach using the RAM method. They rated the appropriateness of statements describing diagnostic and management options for BII on a Likert scale. A modified final survey comprising 140 statements was completed, subdivided into history and physical examination (20), investigations (39), airway management (5), systemic toxicity (23), invasive mechanical ventilation (29) and pharmacotherapy (24). Median appropriateness ratings and the disagreement index (DI) were calculated to classify statements as appropriate, uncertain, or inappropriate., Results: Of 140 statements, 74 were rated as appropriate, 40 as uncertain and 26 as inappropriate. Initial intubation with ≥ 8.0 mm endotracheal tubes, lung protective ventilatory strategies, initial bronchoscopic lavage, serial bronchoscopic lavage for severe BII, nebulised heparin and salbutamol administration for moderate-severe BII and N-acetylcysteine for moderate BII were rated appropriate. Non-protective ventilatory strategies, high-frequency oscillatory ventilation, high-frequency percussive ventilation, prophylactic systemic antibiotics and corticosteroids were rated inappropriate. Experts disagreed (DI ≥ 1) on six statements, classified uncertain: the use of flexible fiberoptic bronchoscopy to guide fluid requirements (DI = 1.52), intubation with endotracheal tubes of internal diameter < 8.0 mm (DI = 1.19), use of airway pressure release ventilation modality (DI = 1.19) and nebulised 5000IU heparin, N-acetylcysteine and salbutamol for mild BII (DI = 1.52, 1.70, 1.36, respectively)., Conclusions: Burns experts mostly agreed on appropriate and inappropriate diagnostic and management criteria of BII as in published guidance. Uncertainty exists as to the optimal diagnosis and management of differing grades of severity of BII. Future research should investigate the accuracy of bronchoscopic grading of BII, the value of bronchial lavage in differing severity groups and the effectiveness of nebulised therapies in different severities of BII., (© 2023. The Author(s).)

Introduction: Hypertrophic scarring is a common and debilitating consequence of burn scars. While there is limited evidence for current treatment options, laser therapy has been shown to be effective, low risk and minimally invasive. This study assesses the use of carbon dioxide lasers and intense pulsed light devices in the treatment of hypertrophic burn scars., Methods: In this case series, patients were recruited from a hypertrophic burn scar waitlist and completed a Patient and Observer Scar Assessment Scale prior to and six weeks after laser therapy. The Nordlys (intense pulsed light) and CO 2 RE (carbon dioxide) systems from Candela Medical were used, with a range of settings used depending on the assessment of the burn scar. The differences between scores were calculated for the total Patient and Observer Scar Assessment Scale score, pain, itch, colour, stiffness, thickness, irregularity and the overall opinion of the scar. Statistical analysis was completed using a paired, two-tailed student T test., Results: A total of 31 patients were recruited for this trial with a range of scar locations, surface areas and mechanism of burn injury. The calculated difference in mean showed a significant reduction for the overall Patient and Observer Scar Assessment Scale score (1.93, p < 0.0001), pain (1.39, p  =  0.0002), itch (1.84, p  =  0.0002), colour (1.97, p < 0.0001), stiffness (2.47, p < 0.0001), thickness (2.1, p < 0.0001), irregularity (1.89, p < 0.0001) and overall opinion (1.58, p  =  0.0003)., Conclusion: Current management options for hypertrophic scarring have limited evidence. Laser therapy presents a minimally invasive procedure that can be completed under topical anaesthetic and has shown to be effective following a single treatment of combined carbon dioxide laser and intense pulsed light device therapy., Lay Summary: Many people will suffer a burn injury throughout their life and up to almost 3 out of 4 people with burn injuries will suffer from hypertrophic scars (a thickened, red and itchy scar). These scars cause distress both due to their appearance and their reduction of function, particularly over a joint or muscle. Laser therapy, in which different wave lengths of light (pulsed light) or gas (carbon dioxide) target the scar, has been found to be effective and have minimal side effects in the management of hypertrophic scars. While individual lasers have been assessed and found to be effective and low risk, the combined use of multiple lasers on the same scar has not been extensively studied. We studied the effectiveness of both light and gas laser therapies on hypertrophic scars. Patients with hypertrophic scars completed a questionnaire that focused on their perspective of their scar (pain, itch, stiffness, thickness, irregularity, overall opinion) prior to the treatment. The patients then underwent laser therapy (with local anaesthetic gel) with either pulsed light and/or carbon dioxide (gas) laser. The type of laser used was decided by the clinician performing the therapy depending on scar location and thickness. Patients then re-completed the subjective survey six weeks following the laser therapy, and the results compared. We learnt that laser therapy (both light, gas and a combination of both) are effective (and low risk) in reducing the subjective burden of the scar for the patient., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Autologous skin grafting has been commonly used in clinics for decades to close large wounds, yet the cellular and molecular interactions between the wound bed and the graft that mediates the wound repair are not fully understood. The aim of this study was to better understand the molecular changes in the wound triggered by autologous and synthetic grafting. Defining the wound changes at the molecular level during grafting sets the basis to test other engineered skin grafts by design. In this study, a full-thickness skin graft (SKH-1 hairless) mouse model was established. An autologous full-thickness skin graft (FTSG) or an acellular fully synthetic Biodegradable Temporising Matrix (BTM) was grafted. The wound bed/grafts were analysed at histological, RNA, and protein levels during the inflammation (day 1), proliferation (day 5), and remodelling (day 21) phases of wound repair. The results showed that in this mouse model, similar to others, inflammatory marker levels, including Il-6 , Cxcl-1 , and Cxcl-5 / 6 , were raised within a day post-wounding. Autologous grafting reduced the expression of these inflammatory markers. This was different from the wounds grafted with synthetic dermal grafts, in which Cxcl-1 and Cxcl-5/6 remained significantly high up to 21 days post-grafting. Autologous skin grafting reduced wound contraction compared to wounds that were left to spontaneously repair. Synthetic grafts contracted significantly more than FTSG by day 21. The observed wound contraction in synthetic grafts was most likely mediated at least partly by myofibroblasts. It is possible that high TGF-β1 levels in days 1-21 were the driving force behind myofibroblast abundance in synthetic grafts, although no evidence of TGF-β1-mediated Connective Tissue Growth Factor (CTGF) upregulation was observed.

Background: Use of intravascular warming catheters following major burns has been shown to be effective to maintain normothermia, but their use may be associated with complications. The aim of this study was to determine what proportion of patients with an intravascular warming catheter developed a potentially catheter-related venous thromboembolism (VTE) and to identify contributing risk factors. Methods: This was a retrospective cohort study of patients admitted to the Victorian Adult Burns Service January 2013 to July 2018 with major burns (TBSA > 20%) who had an ICY TM intravascular warming catheter. Warming catheter insertion and other details were identified with a manual search of the patients' medical records by a single author while incidence of VTE was determined by the coding department from a central database. Results: Forty patients had an intravascular warming catheter inserted during the study period. The number of patients in the catheter group that sustained a VTE was eight (20%), of which four (10%) could have been catheter-related due to the anatomical location. In the cases of the four potentially catheter-related VTE, other preventable VTE risk factors including suboptimal prophylactic anticoagulation ( n = 2), prolonged catheter duration ( n = 1) and prolonged haemoconcentration ( n = 2) were identified. Conclusions: We found 20% of major burns patients with an intravascular warming device had significant VTE; however, only half of these may have been related to the catheter. A careful assessment for each patient that balances risks and benefits should be undertaken prior to using intravascular warming devices.

Introduction: Severe cutaneous adverse reactions (SCAR) are a group of T cell-mediated hypersensitivities associated with significant morbidity, mortality and hospital costs. Clinical phenotypes include Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS) and acute generalised exanthematous pustulosis (AGEP). In this Australasian, multicentre, prospective registry, we plan to examine the clinical presentation, drug causality, genomic predictors, potential diagnostic approaches, treatments and long-term outcomes of SCAR in Australia and New Zealand., Methods and Analysis: Adult and adolescent patients with SCAR including SJS, TEN, DRESS, AGEP and another T cell-mediated hypersensitivity, generalised bullous fixed drug eruption, will be prospectively recruited. A waiver of consent has been granted for some sites to retrospectively include cases which result in early mortality. DNA will be collected for all prospective cases. Blood, blister fluid and skin biopsy sampling is optional and subject to patient consent and site capacity. To develop culprit drug identification and prevention, genomic testing will be performed to confirm human leukocyte antigen (HLA) type and ex vivo testing will be performed via interferon-γ release enzyme linked immunospot assay using collected peripheral blood mononuclear cells. The long-term outcomes of SCAR will be investigated with a 12-month quality of life survey and examination of prescribing and mortality data., Ethics and Dissemination: This study was reviewed and approved by the Austin Health Human Research Ethics Committee (HREC/50791/Austin-19). Results will be published in peer-reviewed journals and presented at relevant conferences., Trial Registration Number: Australian New Zealand Clinical Trials Registry (ACTRN12619000241134)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

This study examines the costs of severe burn injury in Victoria, Australia. It quantifies the funding generated through an activity-based case-mix system for hospital treatment of acute injury and presentations in the subsequent two years and costs of the longer-term burden of burn injury due to premature burn-related deaths and disability. Severe adult burns cases in Victoria from 2007-2016 were identified using the Victorian State Trauma Registry (VSTR). Cases were linked with the Victorian Admitted Episodes Dataset (VAED), Victoria Emergency Minimum Dataset (VEMD), and the National Coronial Information System (NCIS). Hospital re-imbursements and costs of Disability-Adjusted Life Years (DALYs) were calculated using disability weights derived from the EQ-5D-3L questionnaire responses at 24 months post injury. There were 331 patients hospitalised with a burn ≥20% total body surface area (TBSA) from 2007-2016. Total mean re-imbursement (SD) for the acute treatment episode per patient in Australian dollars (AUD) was $87,570 ($97,913). There was significant variation in the number of cases by year and re-imbursement per patient, with high outliers common. Excluding 2009, when 173 people died in bushfires, there were 7749 DALYs which cost $991,872,000. Severe burns are uncommon and variable. Economic treatment costs of severe burns are high, and among survivors there is high incidence of long-term disability and overall burden of injury.

Background: Multidrug resistant organisms (MDROs) occur more commonly in burns patients than in other hospital patients and are an increasingly frequent cause of burn-related mortality. We examined the incidence, trends and risk factors for MDRO acquisition in a specialist burns service housed in an open general surgical ward, and general intensive care unit., Methods: We performed a retrospective study of adult patients admitted with an acute burn injury to our specialist statewide tertiary burns service between July 2014 and October 2020. We linked patient demographics, injury, treatment, and outcome details from our prospective burns service registry to microbiology and antimicrobial prescribing data. The outcome of interest was first MDRO detection, stratified into the following groups of interest: methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE), two groups of Pseudomonas (carbapenem resistant, and piperacillin-tazobactam or cefepime resistant), carbapenem-resistant Acinetobacter species, Stenotrophomonas maltophilia, carbapenem-resistant Enterobacteriaceae (CRE), and extended-spectrum beta-lactamase producing Enterobacteriaceae (ESBL-PE). We used a Cox proportional hazards model to evaluate the association between antibiotic exposure and MDRO acquisition., Results: There were 2,036 acute admissions, of which 230 (11.3%) had at least one MDRO isolated from clinical specimens, most frequently wound swabs. While acquisition rates of individual MDRO groups varied over the study period, acquisition rate of any MDRO was reasonably stable over time. Carbapenem-resistant Pseudomonas was acquired at the highest rate over the study period (3.5/1000 patient days). The 12.8% (29/226) of MDROs isolated within 48 h were predominantly MRSA and Stenotrophomonas. Median (IQR) time from admission to MDRO detection was 10.9 (5.6-20.5) days, ranging from 9.8 (2.7-24.2) for MRSA to 23.6 (15.7-36.0) for carbapenem-resistant P. aeruginosa. Patients with MDROs were older, had more extensive burns, longer length of stay, and were more likely to have operative burn management. We were unable to detect a relationship between antibiotic exposure and emergence of MDROs., Conclusions: MDROs are a common and consistent presence in our burns unit. The pattern of acquisition suggests various causes, including introduction from the community and nosocomial spread. More regular surveillance of incidence and targeted interventions may decrease their prevalence, and limit the development of invasive infection., (© 2022. The Author(s).)