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Objective: Successful endotracheal intubation in the ED requires optimum body positioning. In patients with obesity, the ramp position was suggested to achieve better intubating conditions. However, limited data are available on the airway management practices for patients with obesity in Australasian EDs. The aim of this study was to identify current patient positioning practices during endotracheal intubation and its association with first‐pass success (FPS) at intubation and adverse event (AE) rates in obese and non‐obese populations. Methods: Prospectively collected data from the Australia and New Zealand ED Airway Registry (ANZEDAR) between 2012 and 2019 were analysed. Patients were categorised into two groups according to their weight: <100 kg (non‐obese) or ≥100 kg (obese). Four position categories were investigated; supine, pillow or occipital pad, bed tilt and ramp or head‐up with relation to FPS and complication rate using logistic regression modelling. Results: A total of 3708 intubations from 43 EDs were included. Overall, the non‐obese cohort had a greater FPS rate (85.9%) compared to the obese group (77.0%). The bed tilt position had the highest FPS rate (87.2%), whereas the supine position had the lowest (83.0%). AE rates were highest in the ramp position (31.2%) compared to all other positions (23.8%). Regression analysis showed ramp, or bed tilt positions and a consultant‐level intubator were associated with higher FPS. Obesity, in addition to other factors, was independently associated with lower FPS. Conclusion: Obesity was associated with lower FPS, which could be improved through performing a bed tilt or ramp positioning. [ABSTRACT FROM AUTHOR]

Objective: Describe the characteristics and predictors of mortality for patients who spend more than 24 h in the ED waiting for an in‐patient bed and compare baseline clinical and demographic characteristics between tertiary and non‐tertiary hospitals. Methods: This was a state‐wide analysis data linkage analysis of adult (age >16 years) ED presentations across New South Wales from 2019 to 2020. Cases were included if their mode of separation from ED indicated admission to an in‐patient unit including critical care ward and their ED length of stay was greater than or equal to 24 h. Cases were categorised by service‐related groups based on principle diagnosis. Results: A total of 26 854 eligible cases were identified. The most common diagnosis groups were psychiatry, cardiology and respiratory. The odds ratio (OR) for 30‐day all‐cause mortality in admitted patients with an ED length of stay greater than 24 h were highest in those aged >75 years (OR 15.18, 95% confidence interval [CI] 9.99–23.07, P < 0.001), oncology (OR 10.45, 95% CI 7.93–13.77, P < 0.001) and haematology patients (OR 2.95, 95% CI 2.01–4.33, P < 0.001). Conclusion: Interventions and models of care to address ED access block need to focus on mental health patients, older patients particularly those with cardiorespiratory illness and oncology and haematology patients for whom risk of mortality is disproportionately higher. [ABSTRACT FROM AUTHOR]

Objectives: The present study aimed to describe the characteristics, performance, accuracy and significance of point‐of‐care ultrasound (POCUS) use in the ED, by utilising an expanded version of the ACEM‐mandated special skills placement (SSP) logbook, to develop a novel clinical quality registry. Methods: A prospective, observational study was performed across EDs in Australia and New Zealand over a 12‐month period. Trainees undertaking ACEM‐approved ultrasound (US) SSPs recorded all US scan interpretations and follow‐up imaging reports in an online database. Results: In total, 2647 USs were recorded by 26 special skills trainees across 10 EDs in Australia or New Zealand; of these 2356 scans (89%) were clinically indicated. Overall, 2493 scans (94%) were used for diagnostic assessment, of which 1147 (43%) had abnormal findings. Basic echocardiography, extended Focused Assessment with Sonography in Trauma and right upper quadrant scans were the most commonly used modalities. There were 134 US‐guided procedures logged in the registry. Approximately 36% of scans were reported to alter the original provisional diagnosis, whereas in another 37% of cases, POCUS was thought to confirm the original clinical suspicion. The majority of scans (76.5%) entered into the registry were physically reviewed by the SSP supervisor. Conclusions: This multicentred registry provides a detailed description of the current utilisation of POCUS within special skills US placements across EDs in Australia and New Zealand. This data should inform clinical leaders in emergency US to improve both POCUS education and governance around this important tool. [ABSTRACT FROM AUTHOR]

The use of cricoid pressure (CP) to prevent aspiration during rapid sequence induction (RSI) has become controversial, although CP is considered central to the practice of RSI. There is insufficient research to support its efficacy in reducing aspiration, and emerging concerns it reduces the first‐pass success (FPS) of intubation. This systematic review aims to assess the safety and efficacy of CP during RSI in EDs by investigating its effect on FPS and the incidence of complications, including gastric regurgitation and aspiration. A systematic review of four databases was performed for all primary research investigating CP during RSI in EDs. The primary outcome was FPS; secondary outcomes included complications such as gastric regurgitation, aspiration, hypoxia, hypotension and oesophageal intubation. After screening 4208 citations, three studies were included: one randomised controlled trial (n = 54) investigating the incidence of aspiration during the application of CP and two registry studies (n = 3710) comparing the rate of FPS of RSI with and without CP. The results of these individual studies are not sufficient to draw concrete conclusions but do suggest that aspiration occurs regardless of the application of CP, and that FPS is not reduced by the application of CP. There is insufficient evidence to conclude whether applying CP during RSI in EDs affects the rate of FPS or the incidence of complications such as aspiration. Further research in the ED, including introducing CP usage into other existing airway registries, is needed. [ABSTRACT FROM AUTHOR]

Increased levels of IL-6 are documented in asthma, but its contribution to the pathology is unknown. Asthma is characterized by airway wall thickening due to increased extracellular matrix deposition, inflammation, angiogenesis, and airway smooth muscle (ASM) mass. IL-6 binds to a specific membrane-bound receptor, IL-6 receptor-[alpha] (mIL-6R[alpha]), and subsequently to the signaling protein gp130. Alternatively, IL-6 can bind to soluble IL-6 recpetor-[alpha] (sIL-6R[alpha]) to stimulate membrane receptordeficient cells, a process called trans-signaling. We discovered that primary human ASM cells do not express mIL-6R[alpha] and, therefore, investigated the effect of IL-6 trans-signaling on the pro-remodeling phenotype of ASM. ASM required sIL-6R[alpha] to activate signal transducer and activator 3, with no differences observed between cells from asthmatic subjects compared with controls. Further analysis revealed that IL-6 alone or with sIL-6R[alpha] did not induce release of matrix-stimulating factors (including connective tissue growth factor, fibronectin, or integrins) and had no effect on mast cell adhesion to ASM or ASM proliferation. However, in the presence of sIL-6R[alpha], IL-6 increased eotaxin and VEGF release and may thereby contribute to local inflammation and vessel expansion in airway walls of asthmatic subjects. As levels of sIL-6R[alpha] are increased in asthma, this demonstration of IL-6 trans-signaling in ASM has relevance to the development of airway remodeling. soluble interleukin-6 receptor-[alpha]; gp130; signal transducer and activator 3; asthma; airway remodeling

Objective: Patients intubated in the ED are at an increased risk of post‐intubation hypotension. However, evidence regarding the most appropriate induction agent is lacking. The present study aims to describe and compare the haemodynamic effect of propofol, ketamine and thiopentone during rapid sequence induction. Methods: This is an observational study using data prospectively collected from the Australian and New Zealand Emergency Department Airway Registry between June 2012 and March 2019. The distribution of induction agents across medical and trauma patients were obtained with descriptive statistics. The relationship between induction agent, dose and change in pre‐ and post‐intubation systolic blood pressure (SBP) was described using multivariable logistic regression. The SBP pre‐ and post‐intubation was the primary measure of haemodynamic stability. Results: From the 5063 intubation episodes, 2229 met the inclusion criteria. Of those, 785 (35.2%) patients were induced with thiopentone, 773 (34.7%) with propofol and 671 (30.1%) with ketamine. Of the included population, 396 (17.8%) patients experienced a reduction in pre‐intubation SBP exceeding 20%. Both propofol (P = 0.01) and ketamine (P = 0.01) had an independent and dose‐dependent association with hypotension, noting that a higher proportion of patients induced with ketamine had a shock index exceeding 0.9. Conclusion: Propofol was associated with post‐intubation hypotension and it is recommended clinicians consider using the lowest effective dose to reduce this risk. Reflecting its perceived haemodynamic stability, patients who received ketamine were more likely to have a higher shock index; however, there was also an association with post‐intubation hypotension. [ABSTRACT FROM AUTHOR]

Objective: The aims of the present study were to describe current airway management practices after a failed intubation attempt in Australian and New Zealand EDs and to explore factors associated with second attempt success. Methods: Data were collected from a multicentre airway registry (The Australian and New Zealand Emergency Department Airway Registry). All intubation episodes that required a second attempt between March 2010 and November 2015 were analysed. Analysis for association with success at the second attempt was undertaken for patient factors including predicted difficulty of laryngoscopy, as well as for changes in laryngoscope type, adjunct devices, intubator and intubating manoeuvres. Results: Of the 762 patients with a failed first intubation attempt, 603 (79.1%) were intubated successfully at the second attempt. The majority of second attempts were undertaken by emergency consultants (36.8%) and emergency registrars (34.2%). A change in intubator occurred in 56.5% of intubation episodes and was associated with higher second attempt success (unadjusted odds ratio [OR] 1.85; 95% confidence interval [CI] 1.29–2.65). In 69.7% of second attempts at intubation, there was no change in laryngoscope type. Changes in laryngoscope type, adjunct devices and intubation manoeuvres were not significantly associated with success at the second attempt. In adjusted analyses, second attempt success was higher for a change from a non‐consultant intubator to a consultant intubator from any specialty (adjusted OR 2.31; 95% CI 1.35–3.95) and where laryngoscopy was not predicted to be difficult (adjusted OR 2.58; 95% CI 1.58–4.21). Conclusions: The majority of second intubation attempts were undertaken by emergency consultants and registrars. A change from a non‐consultant intubator to a consultant intubator of any specialty for the second attempt and intubation episodes where laryngoscopy was predicted to be non‐difficult were associated with a higher success rate at intubation. Participation in routine collection and monitoring of airway management practices via a Registry may enable the introduction of appropriate improvements in airway procedures and reduce complication rates. [ABSTRACT FROM AUTHOR]

Abstract Background Activated mast cells are present within airway smooth muscle (ASM) bundles in eosinophilic asthma. ASM production of the chemokine CXCL10 plays a role in their recruitment. Thus the effects of glucocorticoids (fluticasone, budesonide), long-acting β2-agonists (salmeterol, formoterol) and thiazolidinediones (ciglitazone, rosiglitazone) on CXCL10 production by ASM cells (ASMC) from people with and without asthma were investigated in vitro. Methods Confluent serum-deprived cells were treated with the agents before and during cytokine stimulation for 0-24 h. CXCL10 protein/mRNA, IκB-α levels and p65 activity were measured using ELISA, RT PCR, immunoblotting and p65 activity assays respectively. Data were analysed using ANOVA followed by Fisher’s post-hoc test. Results Fluticasone and/or salmeterol at 1 and 100 nM inhibited CXCL10 release induced by IL-1β and TNF-α, but not IFNγ or all three cytokines (cytomix). The latter was also not affected by budesonide and formoterol. In asthmatic ASMC low salmeterol, but not formoterol, concentrations increased cytomix-induced CXCL10 release and at 0.01 nM enhanced NF-κB activity. Salmeterol 0.1nM together with fluticasone 0.1 and 10 nM still increased CXCL10 release. The thiazolidinediones ciglitazone and rosiglitazone (at 25 and 100 μM) inhibited cytomix-induced CXCL10 release but these inhibitory effects were not prevented by the PPAR-g antagonist GW9662. Ciglitazone did not affect early NF-κB activity and CXCL10 mRNA production. Conclusions Thus the thiazolidinediones inhibited asthmatic ASMC CXCL10 release under conditions when common asthma therapies were ineffective or enhanced it. They may provide an alternative strategy to reduce mast cell-ASM interactions and restore normal airway physiology in asthma.

Background: An emergency front‐of‐neck access (eFONA), also called can't intubate, can't oxygenate (CICO) rescue, is a rare event. Little is known about the performance of surgical or percutaneous airways in EDs across Australia and New Zealand. Objective: To describe the management of cases resulting in an eFONA, and recorded in The Australian and New Zealand Emergency Department Airway Registry (ANZEDAR). Methods: A retrospective case series and review of ED patients undergoing surgical or percutaneous airways. Data were collected prospectively over 60 months between 2010 and 2015 from 44 participating EDs. Results: An eFONA/CICO rescue airway was performed on 15 adult patients: 14 cricothyroidotomies (0.3% of registry intubations) and one tracheostomy. The indication for intubation was 60% trauma and 40% medical aetiologies. The intubator specialty was emergency medicine in eight (53.3%) episodes. Thirteen (86.7%) cricothyroidotomies and the sole tracheostomy (6.7%) were performed at major referral hospitals with 12 (80%) surgical airways out of hours. In four (26.7%) cases, cricothyroidotomy was performed as the primary intubation method. Pre‐oxygenation techniques were used in 14 (93.3%) episodes; apnoeic oxygenation in four (26.7%). Conclusions: Most cases demonstrated deviations from standard difficult airway practice, which may have increased the likelihood of performance of a surgical airway, and its increased likelihood out of hours. Our findings may inform training strategies to improve care for ED patients requiring this critical intervention. We recommend further discussion of proposed standard terminology for emergency surgical or percutaneous airways, to facilitate clear crisis communication. [ABSTRACT FROM AUTHOR]

Apnoeic oxygenation (ApOx) has been demonstrated to reduce the incidence of desaturation, although evidence of benefit has been conflicting depending on the technique used. The aim of this study was to compare the incidence of desaturation between patients who received ApOx via conventional nasal cannula (NC) and those who did not, using a large, multicentre airway registry.Methods: This study is an analysis of 24 months of prospectively collected data in the Australia and New Zealand Emergency Department Airway Registry (June 2013-June 2015). The registry includes information on all intubated adults from 43 emergency departments. Patients intubated during cardiac arrest (n=393), those who received active ventilation prior to the first intubation attempt (n=486), and where the use of ApOx was not recorded either way (n=312) were excluded. The proportion of patients who desaturated (Sa02 <93) in the group that received ApOx and those that did not were compared. To evaluate the association of ApOx with patient desaturation, a logistic regression model based on factors expected to influence desaturation was performed.Results: Of 2519 patients analysed, 1669 (66.3%) received ApOx via NC while 850 (33.7%) did not. Desaturation in the cohort receiving ApOx was 10.4% compared with standard care (no ApOx) 13.7%. ApOx had a protective effect for desaturation (OR 0.71 95% CI 0.53 to 0.95). Single intubation attempt was associated with reduced risk of desaturation of (OR 0.10, 95% CI 0.06 to 0.17); this was increased on second attempt (OR 0.37, 95% CI 0.21 to 0.68). Desaturation was also associated with the physician recording that they had anticipated a difficult airway (OR 1.83, 95% CI 1.34 to 2.48).Conclusion: This large multicentre registry study provides evidence that ApOx delivered through a conventional NC is associated with a lower incidence of desaturation in patients undergoing rapid sequence intubation.Trial Registration Number: ACTRN12613001052729. [ABSTRACT FROM AUTHOR]

Objectives: To describe the epidemiology, clinical practice and outcomes of paediatric ED intubation in Australia and New Zealand. Method: Prospectively collected airway management audit data from 43 EDs in Australia and New Zealand that was submitted to the Australia and New Zealand Emergency Department Airway Registry between 2010 and 2015. Results: Paediatric cases accounted for 4.94% (270/5463) of cases (median age = 3, interquartile range [IQR] = 2–9). A median of 5 (IQR = 2–9) intubations were reported per department per year. Most intubations were performed for medical indications (72.2%), including seizure (25.2%) and respiratory failure (15.2%). Patients were physiologically compromised prior to intubation with 69.5% comatose, 50.9% outside of the normal age‐adjusted range for respiratory rate, 15.9% hypoxic and 12.6% hypotensive. Complication rate was 33.3% and desaturation was the most common (18.5%). The ED mortality rate was 3.8%. First pass success (FPS) was 80% (95% CI 75.2–84.8). Infants less than 1 year of age had lower FPS, higher rates of difficult laryngoscopy and higher rates of desaturation than other age groups. Conclusion: Paediatric intubation in Australasian EDs is rare from a departmental and individual provider viewpoint. Success rates are similar to contemporary international registries. Complications are common and ongoing collaborative multicentre audit with resultant quality improvement is desirable to facilitate improved success and reduced complications. [ABSTRACT FROM AUTHOR]

Objectives: To determine the impact of the emergency physiotherapy service provided through different models of care on service quality indicators, patient flow, staff and patient satisfaction. Method: A mixed method prospective observation study was conducted between September 2014 and April 2015 in 19 EDs where a physiotherapy service is provided. Results: Patients seen by the primary contact physiotherapist (PCP) were associated with a significant reduction in ED length of stay by 108 min, wait time to treatment by 10 min (n = 4 EDs) and time‐to‐first analgesia by 18 min (n = 19 EDs) compared to those seen through usual care processes. Patients who received care by a doctor first and then physiotherapist (secondary contact model) had a prolonged length of stay compared to other care pathways. High levels of satisfaction with the PCP role were expressed by ED staff (n = 17 EDs) and patients (n = 19 EDs). More than 95% of patients who received care by PCP were satisfied with the management of their condition, understood the advice and discharge information provided and had enough time to ask questions. Conclusion: ED implementation of the PCP model may improve patient flow and efficiency of clinical skill utilisation in a complex, high demand workplace. [ABSTRACT FROM AUTHOR]

Objective: To study ED utilisation by people aged 100 years and over with a focus on patient demographics, reasons for presentation and patient flow factors. Methods: This is a retrospective descriptive analysis of linked ED Data Collection Registry for presentations to New South Wales (NSW) EDs over a 5 year period. Patients were included if they presented to an ED and were aged 100 years and over at the time of presentation. Demographics, triage category, presenting problem, ED length of stay, disposition and ED re‐presentation were determined for this age group. Results: A total of 4033 presentations to 115 NSW EDs during 2010–2014 were analysed. We found that 78% of the patients were females and 76% still living at home. This group were the second most common age group to present to ED, after the 90–99 year age group, with 87% arriving via ambulance. Most presentations were triaged as a category 3 or 4, with the most common presenting problem being because of injury (28.5%) followed by respiratory disease (11.4%) and cardiovascular disease (10.0%). Overall, 64% required hospital admission and the average length of stay for all patients was 5.7 h. Conclusions: Centenarians ED presentations are increasing over time with injuries as the most common reason for presentation. Most patients have prolonged ED length of stay and many require hospital admission. Early streaming of these patients through specialised geriatric assessment units may be more appropriate to reduce the demand on EDs and improve patient care. Models that facilitate rapid access to supported living arrangements and improved advanced care planning may be more realistic for many centenarians and different models of care need to be considered for this age group. [ABSTRACT FROM AUTHOR]

Background: Emergency departments (EDs) are pressured environment where patients with supportive and palliative care needs may not be identified. We aimed to test the predictive ability of the CriSTAL (Criteria for Screening and Triaging to Appropriate aLternative care) checklist to flag patients at risk of death within 3 months who may benefit from timely end‐of‐life discussions. Methods: Prospective cohorts of >65‐year‐old patients admitted for at least one night via EDs in five Australian hospitals and one Irish hospital. Purpose‐trained nurses and medical students screened for frailty using two instruments concurrently and completed the other risk factors on the CriSTAL tool at admission. Postdischarge telephone follow‐up was used to determine survival status. Logistic regression and bootstrapping techniques were used to test the predictive accuracy of CriSTAL for death within 90 days of admission as primary outcome. Predictability of in‐hospital death was the secondary outcome. Results: A total of 1,182 patients, with median age 76 to 80 years (IRE‐AUS), were included. The deceased had significantly higher mean CriSTAL with Australian mean of 8.1 (95% confidence interval [CI] = 7.7–8.6) versus 5.7 (95% CI = 5.1–6.2) and Irish mean of 7.7 (95% CI = 6.9–8.5) versus 5.7 (95% CI = 5.1–6.2). The model with Fried frailty score was optimal for the derivation (Australian) cohort but prediction with the Clinical Frailty Scale (CFS) was also good (areas under the receiver‐operating characteristic [AUROC] = 0.825 and 0.81, respectively). Values for the validation (Irish) cohort were AUROC = 0.70 with Fried and 0.77 using CFS. A minimum of five of 29 variables were sufficient for accurate prediction, and a cut point of 7+ or 6+ depending on the cohort was strongly indicative of risk of death. The most significant independent predictor of short‐term death in both cohorts was frailty, carrying a twofold risk of death. CriSTAL's accuracy for in‐hospital death prediction was also good (AUROC = 0.795 and 0.81 in Australia and Ireland, respectively), with high specificity and negative predictive values. Conclusions: The modified CriSTAL tool (with CFS instead of Fried's frailty instrument) had good discriminant power to improve certainty of short‐term mortality prediction in both health systems. The predictive ability of models is anticipated to help clinicians gain confidence in initiating earlier end‐of‐life discussions. The practicalities of embedding screening for risk of death in routine practice warrant further investigation. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to quantify the proportion of patients undergoing rapid sequence intubation using ketamine in Australian and New Zealand EDs between 2010 and 2015. Methods: The Australian and New Zealand Emergency Department Airway Registry is a multicentre airway registry prospectively capturing data from 43 sites. Data on demographics and physiology, the attending staff and indication for intubation were recorded. The primary outcome was the annual percentage of patients intubated with ketamine. A logistic regression analysis was conducted to evaluate the factors associated with ketamine use. Results: A total of 4658 patients met inclusion criteria. The annual incidence of ketamine use increased from 5% to 28% over the study period (P < 0.0001). In the logistic regression analysis, the presence of an emergency physician as a team leader was the strongest predictor of ketamine use (odds ratio [OR] 1.83, 95% confidence interval [CI] 1.44–2.34). The OR for an increase in one point on the Glasgow Coma Scale was 1.10 (95% CI 1.07–1.12), whereas an increase of 1 mmHg of systolic blood pressure had an OR of 0.98 (95% CI 0.98–0.99). Intubation occurring in a major referral hospital had an OR of 0.68 (95% CI 0.56–0.82), while trauma conferred an OR of 1.38 (95% CI 1.25–1.53). Conclusions: Ketamine use increased between 2010 and 2015. Lower systolic blood pressure, the presence of an emergency medicine team leader, trauma and a higher Glasgow Coma Scale were associated with increased odds of ketamine use. Intubation occurring in a major referral centre was associated with lower odds of ketamine use. [ABSTRACT FROM AUTHOR]

The bioactive sphingolipid sphingosine 1-phosphate (S1P) is found in increased amounts in the airways of asthmatics. S1P can regulate airway smooth muscle functions associated with asthmatic inflammation and remodeling, including cytokine secretion. To date however, whether S1P induces secretion of an important chemokine responsible for neutrophilia in airway inflammation – IL-8 – was unexplored. The aim of this study was to investigate whether S1P induces IL-8 gene expression and secretion to enhance neutrophil chemotaxis in vitro, as well as examine the molecular mechanisms responsible for repression by the corticosteroid dexamethasone. We show that S1P upregulates IL-8 secretion from ASM cells and enhance neutrophil chemotaxis in vitro. The corticosteroid dexamethasone significantly represses IL-8 mRNA expression and protein secretion in a concentration- and time-dependent manner. Additionally, we reveal that S1P-induced IL-8 secretion is p38 MAPK and ERK-dependent and that these key phosphoproteins act on the downstream effector mitogen- and stress-activated kinase 1 (MSK1) to control secretion of the neutrophil chemoattractant cytokine IL-8. The functional relevance of this in vitro data was demonstrated by neutrophil chemotaxis assays where S1P-induced effects can be significantly attenuated by pretreatment with dexamethasone, pharmacological inhibition of p38 MAPK- or ERK-mediated pathways, or by knocking down MSK-1 with siRNA. Taken together, our study reveals the molecular pathways responsible for IL-8 secretion from ASM cells in response to S1P and indicates ways in which the impact on IL-8-driven neutrophilia may be lessened. [ABSTRACT FROM AUTHOR]

Mitogen-activated protein kinase phosphatase 1 (MKP-1) represses MAPK-driven signalling and plays an important anti-inflammatory role in asthma and airway remodelling. Although MKP-1 is corticosteroid-responsive and increased by cAMP-mediated signalling, the upregulation of this critical anti-inflammatory protein by long-acting β2-agonists and clinically-used corticosteroids has been incompletely examined to date. To address this, we investigated MKP-1 gene expression and protein upregulation induced by two long-acting β2-agonists (salmeterol and formoterol), alone or in combination with the corticosteroid fluticasone propionate (abbreviated as fluticasone) in primary human airway smooth muscle (ASM) cells in vitro. β2-agonists increased MKP-1 protein in a rapid but transient manner, while fluticasone induced sustained upregulation. Together, long-acting β2-agonists increased fluticasone-induced MKP-1 and modulated ASM synthetic function (measured by interleukin 6 (IL-6) and interleukin 8 (IL-8) secretion). As IL-6 expression (like MKP-1) is cAMP/adenylate cyclase-mediated, the long-acting β2-agonist formoterol increased IL-6 mRNA expression and secretion. Nevertheless, when added in combination with fluticasone, β2-agonists significantly repressed IL-6 secretion induced by tumour necrosis factor α (TNFα). Conversely, as IL-8 is not cAMP-responsive, β2-agonists significantly inhibited TNFα-induced IL-8 in combination with fluticasone, where fluticasone alone was without repressive effect. In summary, long-acting β2-agonists increase fluticasone-induced MKP-1 in ASM cells and repress synthetic function of this immunomodulatory airway cell type. [ABSTRACT FROM AUTHOR]

CXCL10 (IP10) is involved in mast cell migration to airway smooth muscle (ASM) bundles in asthma. We aimed to investigate the role of cytokineinduced MAPK activation in CXCL10 production by ASM cells from people with and without asthma. Confluent growth-arrested ASM cells were treated with inhibitors of the MAPKs ERK, p38, and JNK and transcription factor NF-κB, or vehicle, and stimulated with IL-1β, TNF-α, or IFN-γ, alone or combined (cytomix). CXCL10 mRNA and protein, JNK, NF-κB p65 phosphorylation, and Iκ-Bα protein degradation were assessed using real-time PCR, ELISA, and immunoblotting, respectively. Cytomix, IL-1β, and TNF-α induced CXCL10 mRNA expression more rapidly in asthmatic than nonasthmatic ASM cells. IL-1β and/or TNF-α combined with IFN-γ synergistically increased asthmatic ASM cell CXCL10 release. Inhibitor effects were similar in asthmatic and nonasthmatic cells, but cytomix-induced release was least affected, with only JNK and NF-κB inhibitors halving it. Notably, JNK phosphorylation was markedly less in asthmatic compared with nonasthmatic cells. However, in both, the JNK inhibitor SP600125 reduced JNK phosphorylation and CXCL10 mRNA levels but did not affect CXCL10 mRNA stability or Iκ-Bα degradation. Together, the JNK and NF-κB inhibitors completely inhibited their CXCL10 release. We concluded that, in asthmatic compared with nonasthmatic ASM cells, JNK activation was reduced and CXCL10 gene expression was more rapid following cytomix stimulation. However, in both, JNK activation did not regulate early events leading to NF-κB activation. Thus JNK and NF-κB provide independent therapeutic targets for limiting CXCL10 production and mast cell migration to the ASM in asthma. [ABSTRACT FROM AUTHOR]

In asthma, airway smooth muscle (ASM) chemokine secretion can induce mast cell recruitment into the airways. The functions of the mast cell chemoattractant CXCL10, and other chemokines, are regulated by binding to heparan sulphates such as syndecan-4. This study is the first demonstration that airway smooth muscle cells (ASMC) from people with and without asthma express and shed syndecan-4 under basal conditions. Syndecan-4 shedding was enhanced by stimulation for 24 h with the Th1 cytokines interleukin-1;β (IL-1β) or tumor necrosis factor-α (TNF-α), but not interferon-γ (IFNγ), nor the Th2 cytokines IL-4 and IL-13. ASMC stimulation with IL-1β, TNF-α, and IFNγ (cytomix) induced the highest level of syndecan-4 shedding. Nonasthmatic and asthmatic ASM cell-associated syndecan-4 protein expression was also increased by TNF-α or cytomix at 4-8 h, with the highest levels detected in cytomix-stimulated asthmatic cells. Cell-associated syndecan-4 levels were decreased by 24 h, whereas shedding remained elevated at 24 h, consistent with newly synthesized syndecan-4 being shed. Inhibition of ASMC matrix metalloproteinase-2 did not prevent syndecan-4 shedding, whereas inhibition of ERK MAPK activation reduced shedding from cytomix-stimulated ASMC. Although ERK inhibition had no effect on syndecan-4 mRNA levels stimulated by cytomix, it did cause an increase in cell-associated syndecan-4 levels, consistent with the shedding being inhibited. In conclusion, ASMC produce and shed syndecan-4 and although this is increased by the Th1 cytokines, the MAPK ERK only regulates shedding. ASMC syndecan-4 production during Th1 inflammatory conditions may regulate chemokine activity and mast cell recruitment to the ASM in asthma. [ABSTRACT FROM AUTHOR]

Introduction: Poor patient assessment results in undetected clinical deterioration. Yet, there is no standardised assessment framework for >29 000 Australian emergency nurses. To reduce clinical variation and increase safety and quality of initial emergency nursing care, the evidence-based emergency nursing framework HIRAID (History, Identify Red flags, Assessment, Interventions, Diagnostics, communication and reassessment) was developed and piloted. This paper presents the rationale and protocol for a multicentre clinical trial of HIRAID., Methods and Analysis: Using an effectiveness-implementation hybrid design, the study incorporates a stepped-wedge cluster randomised controlled trial of HIRAID at 31 emergency departments (EDs) in New South Wales, Victoria and Queensland. The primary outcomes are incidence of inpatient deterioration related to ED care, time to analgesia, patient satisfaction and medical satisfaction with nursing clinical handover (effectiveness). Strategies that optimise HIRAID uptake (implementation) and implementation fidelity will be determined to assess if HIRAID was implemented as intended at all sites., Ethics and Dissemination: Ethics has been approved for NSW sites through Greater Western Human Research Ethics Committee (2020/ETH02164), and for Victoria and Queensland sites through Royal Brisbane & Woman's Hospital Human Research Ethics Committee (2021/QRBW/80026). The final phase of the study will integrate the findings in a toolkit for national rollout. A dissemination, communications (variety of platforms) and upscaling strategy will be designed and actioned with the organisations that influence state and national level health policy and emergency nurse education, including the Australian Commission for Quality and Safety in Health Care. Scaling up of findings could be achieved by embedding HIRAID into national transition to nursing programmes, 'business as usual' ED training schedules and university curricula., Trial Registration Number: ACTRN12621001456842., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Apnoeic oxygenation (ApOx) has been demonstrated to reduce the incidence of desaturation, although evidence of benefit has been conflicting depending on the technique used. The aim of this study was to compare the incidence of desaturation between patients who received ApOx via conventional nasal cannula (NC) and those who did not, using a large, multicentre airway registry., Methods: This study is an analysis of 24 months of prospectively collected data in the Australia and New Zealand Emergency Department Airway Registry (June 2013-June 2015). The registry includes information on all intubated adults from 43 emergency departments. Patients intubated during cardiac arrest (n=393), those who received active ventilation prior to the first intubation attempt (n=486), and where the use of ApOx was not recorded either way (n=312) were excluded. The proportion of patients who desaturated (Sa0 2 <93) in the group that received ApOx and those that did not were compared. To evaluate the association of ApOx with patient desaturation, a logistic regression model based on factors expected to influence desaturation was performed., Results: Of 2519 patients analysed, 1669 (66.3%) received ApOx via NC while 850 (33.7%) did not. Desaturation in the cohort receiving ApOx was 10.4% compared with standard care (no ApOx) 13.7%. ApOx had a protective effect for desaturation (OR 0.71 95% CI 0.53 to 0.95). Single intubation attempt was associated with reduced risk of desaturation of (OR 0.10, 95% CI 0.06 to 0.17); this was increased on second attempt (OR 0.37, 95% CI 0.21 to 0.68). Desaturation was also associated with the physician recording that they had anticipated a difficult airway (OR 1.83, 95% CI 1.34 to 2.48)., Conclusion: This large multicentre registry study provides evidence that ApOx delivered through a conventional NC is associated with a lower incidence of desaturation in patients undergoing rapid sequence intubation., Trial Registration Number: ACTRN12613001052729., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Despite being a preventable cause of death, drowning is a global public health threat. Australia records an average of 288 unintentional drowning deaths per year; an estimated annual economic burden of $1.24 billion AUD ($2017). On average, a further 712 hospitalisations occur due to non-fatal drowning annually. The Australian state of New South Wales (NSW) is the most populous and accounts for 34% of the average fatal drowning burden. This study aims to explore the demographics and outcome of patients who are admitted to hospitals for drowning in NSW and also investigates prediction of patients' outcome based on accessible data., Methods and Analysis: This protocol describes a retrospective, cross-sectional data linkage study across secondary data sources for any person (adult or paediatric) who was transferred by NSW Ambulance services and/or admitted to a NSW hospital for fatal or non-fatal drowning between 1/1/2010 and 31/12/2019. The NSW Admitted Patient Data Collection will provide data on admitted patients' characteristics and provided care in NSW hospitals. In order to map patients' pathways of care, data will be linked with NSW Ambulance Data Collection and the NSW Emergency Department Data Collection. Finally patient's mortality will be assessed via linkage with NSW Mortality data, which is made up of the NSW Register of Births, Deaths and Marriages and a Cause of Death Unit Record File. Regression analyses will be used to identify predicting values of independent variables with study outcomes., Ethics and Dissemination: This study has been approved by the NSW Population & Health Services Research Ethics Committee. Results will be disseminated through peer-reviewed publications, mass media releases and at academic conferences. The study will provide outcome data for drowning patients across NSW and study results will provide data to deliver evidence-informed recommendations for improving patient care, including updating relevant guidelines., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Emergency departments (EDs) are pressured environment where patients with supportive and palliative care needs may not be identified. We aimed to test the predictive ability of the CriSTAL (Criteria for Screening and Triaging to Appropriate aLternative care) checklist to flag patients at risk of death within 3 months who may benefit from timely end-of-life discussions., Methods: Prospective cohorts of >65-year-old patients admitted for at least one night via EDs in five Australian hospitals and one Irish hospital. Purpose-trained nurses and medical students screened for frailty using two instruments concurrently and completed the other risk factors on the CriSTAL tool at admission. Postdischarge telephone follow-up was used to determine survival status. Logistic regression and bootstrapping techniques were used to test the predictive accuracy of CriSTAL for death within 90 days of admission as primary outcome. Predictability of in-hospital death was the secondary outcome., Results: A total of 1,182 patients, with median age 76 to 80 years (IRE-AUS), were included. The deceased had significantly higher mean CriSTAL with Australian mean of 8.1 (95% confidence interval [CI] = 7.7-8.6) versus 5.7 (95% CI = 5.1-6.2) and Irish mean of 7.7 (95% CI = 6.9-8.5) versus 5.7 (95% CI = 5.1-6.2). The model with Fried frailty score was optimal for the derivation (Australian) cohort but prediction with the Clinical Frailty Scale (CFS) was also good (areas under the receiver-operating characteristic [AUROC] = 0.825 and 0.81, respectively). Values for the validation (Irish) cohort were AUROC = 0.70 with Fried and 0.77 using CFS. A minimum of five of 29 variables were sufficient for accurate prediction, and a cut point of 7+ or 6+ depending on the cohort was strongly indicative of risk of death. The most significant independent predictor of short-term death in both cohorts was frailty, carrying a twofold risk of death. CriSTAL's accuracy for in-hospital death prediction was also good (AUROC = 0.795 and 0.81 in Australia and Ireland, respectively), with high specificity and negative predictive values., Conclusions: The modified CriSTAL tool (with CFS instead of Fried's frailty instrument) had good discriminant power to improve certainty of short-term mortality prediction in both health systems. The predictive ability of models is anticipated to help clinicians gain confidence in initiating earlier end-of-life discussions. The practicalities of embedding screening for risk of death in routine practice warrant further investigation., (© 2018 The Authors. Academic Emergency Medicine published by Wiley Periodicals, Inc. on behalf of Society for Academic Emergency Medicine (SAEM).)

We hypothesised that the response to cigarette smoke in airway smooth muscle (ASM) cells from smokers with chronic obstructive pulmonary disease (COPD) would be intrinsically different from smokers without COPD, producing greater pro-inflammatory mediators and factors relating to airway remodelling. ASM cells were obtained from smokers with or without COPD, and then stimulated with cigarette smoke extract (CSE) or transforming growth factor-β1. The production of chemokines and matrix metalloproteinases (MMPs) were measured by ELISA, and the deposition of collagens by extracellular matrix ELISA. The effects of CSE on cell attachment and wound healing were measured by toluidine blue attachment and cell tracker green wound healing assays. CSE increased the release of CXCL8 and CXCL1 from human ASM cells, and cells from smokers with COPD produced more CSE-induced CXCL1. The production of MMP-1, -3 and -10, and the deposition of collagen VIII alpha 1 (COL8A1) were increased by CSE, especially in the COPD group which had higher production of MMP-1 and deposition of COL8A1. CSE decreased ASM cell attachment and wound healing in the COPD group only. ASM cells from smokers with COPD were more sensitive to CSE stimulation, which may explain, in part, why some smokers develop COPD., (©ERS 2014.)

In asthma, airway smooth muscle (ASM) chemokine secretion can induce mast cell recruitment into the airways. The functions of the mast cell chemoattractant CXCL10, and other chemokines, are regulated by binding to heparan sulphates such as syndecan-4. This study is the first demonstration that airway smooth muscle cells (ASMC) from people with and without asthma express and shed syndecan-4 under basal conditions. Syndecan-4 shedding was enhanced by stimulation for 24 h with the Th1 cytokines interleukin-1β (IL-1β) or tumor necrosis factor-α (TNF-α), but not interferon-γ (IFNγ), nor the Th2 cytokines IL-4 and IL-13. ASMC stimulation with IL-1β, TNF-α, and IFNγ (cytomix) induced the highest level of syndecan-4 shedding. Nonasthmatic and asthmatic ASM cell-associated syndecan-4 protein expression was also increased by TNF-α or cytomix at 4-8 h, with the highest levels detected in cytomix-stimulated asthmatic cells. Cell-associated syndecan-4 levels were decreased by 24 h, whereas shedding remained elevated at 24 h, consistent with newly synthesized syndecan-4 being shed. Inhibition of ASMC matrix metalloproteinase-2 did not prevent syndecan-4 shedding, whereas inhibition of ERK MAPK activation reduced shedding from cytomix-stimulated ASMC. Although ERK inhibition had no effect on syndecan-4 mRNA levels stimulated by cytomix, it did cause an increase in cell-associated syndecan-4 levels, consistent with the shedding being inhibited. In conclusion, ASMC produce and shed syndecan-4 and although this is increased by the Th1 cytokines, the MAPK ERK only regulates shedding. ASMC syndecan-4 production during Th1 inflammatory conditions may regulate chemokine activity and mast cell recruitment to the ASM in asthma.