Prospective validation of a checklist to predict short-term death in older patients after emergency department admission in Australia and Ireland

Abstract 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

Paediatric intubation in Australasian emergency departments : A report from the ANZEDAR

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

Current airway management practices after a failed intubation attempt in Australian and New Zealand emergency departments

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

Regulation of pulmonary inflammation by mesenchymal cells

Pulmonary inflammation and tissue remodelling are common elements of chronic respiratory diseases such as asthma, chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), and pulmonary hypertension (PH). In disease, pulmonary mesenchymal cells not only contribute to tissue remodelling, but also have an important role in pulmonary inflammation. This review will describe the immunomodulatory functions of pulmonary mesenchymal cells, such as airway smooth muscle (ASM) cells and lung fibroblasts, in chronic respiratory disease. An important theme of the review is that pulmonary mesenchymal cells not only respond to inflammatory mediators, but also produce their own mediators, whether pro-inflammatory or pro-resolving, which influence the quantity and quality of the lung immune response. The notion that defective pro-inflammatory or pro-resolving signalling in these cells potentially contributes to disease progression is also discussed. Finally, the concept of specifically targeting pulmonary mesenchymal cell immunomodulatory function to improve therapeutic control of chronic respiratory disease is considered. (C) 2014 Elsevier Ltd. All rights reserved

Thiazolidinediones inhibit airway smooth muscle release of the chemokine CXCL10: in vitro comparison with current asthma therapies

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.</p

S1P induces IL-8 secretion via a MSK1 dependent pathway and MSK1 knock-down by siRNA attenuates S1P-induced neutrophil chemotaxis.

<p>ASM cells were transiently transfected using nucleofection with scrambled control or MSK1 siRNA, growth-arrested, then treated for 24 h with vehicle or S1P (1 μM). (A) To confirm that MSK1 siRNA reduces protein levels of MSK1, cells were lysed and immunoblotted for MSK1, using α-tubulin as the loading control. To measure the effect of MSK1 knock-down on IL-8 inducibility and neutrophil chemotaxis, supernatants were removed and (B) IL-8 protein measured by ELISA and (C) neutrophil chemotaxis assessed using microchemotaxis chambers. Results are expressed as: (A) representative Western blots; (B) % S1P-induced IL-8 secretion in cells transfected with scrambled control; or (C) % S1P-induced neutrophil chemotaxis in the corresponding conditioned media (data are mean+SEM values from n = 6 primary ASM cell lines). Statistical analysis was performed using the Student's unpaired <i>t</i> test where * indicates that knocking down MSK-1 significantly attenuates S1P-induced effects (<i>P</i><0.05).</p

IL-8 induced by S1P causes human neutrophil chemotaxis <i>in vitro</i> and this can be repressed by corticosteroids or by blocking the p38 MAPK- or ERK-mediated pathways.

<p>Chemotaxis of human neutrophils toward conditioned media from growth-arrested ASM cells pretreated with vehicle, dexamethasone (100 nM), SB203580 (1 μM) or PD98059 (10 μM), followed by treatment with vehicle or S1P (1 μM) for 24 h, was measured using microchemotaxis chambers. Results are expressed as cells per high-power (x200) field. Statistical analysis was performed using the Student's unpaired <i>t</i> test where § denotes a significant effect of S1P on neutrophil chemotaxis, while * denotes significant repression (<i>P</i><0.05). Data are mean+SEM values using conditioned media from n = 3 primary ASM cell lines.</p

The bioactive sphingolipid S1P induces secretion of IL-8 from ASM cells, but this can be repressed by the corticosteroid dexamethasone in a concentration-dependent manner.

<p>(A) Growth-arrested ASM cells were treated with vehicle or S1P (1 μM) for 24 h and IL-8 secretion measured by ELISA. Statistical analysis was performed using the Student's unpaired <i>t</i> test, where § denotes a significant effect of S1P (<i>P</i><0.05). (B) To demonstrate corticosteroid-mediated repression of S1P-induced IL-8 secretion we then pretreated growth-arrested ASM cells for 1 h with vehicle or dexamethasone (0.0001-1M), before stimulation for 24 h with S1P (1 μM). IL-8 protein was measured by ELISA and results expressed as % S1P-induced IL-8 secretion at 24 h. Statistical analysis was performed using one-way ANOVA then Fisher's post-hoc multiple comparison test, where * denotes significant repression by dexamethasone (<i>P</i><0.05). Data are mean+SEM values from n = 12 primary ASM cell lines.</p