Prehospital Blood Transfusion: A Cross-Sectional Study of Prehospital and Retrieval Medicine Services across Australia & Aotearoa-New Zealand.

BACKGROUND: The frequency and type of prehospital blood product delivery across Australia and Aotearoa-New Zealand is unknown. This study aims to describe transfusion practice across different services in the two nations, as well as identifying potential barriers to the carriage of blood products. METHODOLOGY: Prehospital and retrieval medicine services operating teams of doctors, specialist paramedics, and/or flight nurses out of specialty bases across Australia and Aotearoa-New Zealand were sent a standardized questionnaire regarding their base characteristics and their current blood transfusion practice. Bases that only performed inter-hospital transfers or search & rescue operations were excluded. Bases were queried on personnel, equipment, transport times, type and volume of blood products carried, frequency of use, and barriers to implementation for those without prehospital blood transfusion programs. RESULTS: 64 bases were identified and contacted, of which 5 were excluded and 45 of the remaining 59 (76.3%) responded. 62% (28/45) of respondents routinely carry prehospital blood products. 78.6% (22/28) carried packed red blood cells (PRBC) only, 14.3% (4/28) carried both PRBC and plasma, and 1 service (3.6%) carried whole blood. The mean number of units of blood product carried was 3.3 (SD 0.82). 2 bases (7.1%) carried fibrinogen concentrate. All services carried tranexamic acid and calcium. 734 patients received a blood transfusion in 2021, with trauma being the most common indication (552, 75.2%). Base characteristics varied significantly in staffing, vehicle platform and transfer times. The median transfer time from scene to hospital was 65 min (IQR of 40-92). Services without access to prehospital blood products identified multiple barriers to implementation, including training and supply chain. CONCLUSION: Approximately two-thirds of prehospital services operating advanced teams across Australia and Aotearoa-New Zealand carried blood products and there was wide variation both in the type and number of blood products carried by each base. Multiple barriers to the carriage of blood by all bases were reported, which have implications for service equity. Transfer times are generally long in Australia and Aotearoa-New Zealand, which may impact the generalizability of overseas research performed in prehospital systems with significantly shorter transfer times to services operating in Australia and Aotearoa-New Zealand.

Alfentanil versus fentanyl for emergency department rapid sequence induction with ketamine: A-FAKT, a pilot randomized trial.

BACKGROUND: Fentanyl is often administered during rapid sequence induction of anesthesia (RSI) in the emergency department (ED) to ameliorate the hypertensive response that may occur. Due to its more rapid onset, the use of alfentanil may be more consistent with both the onset time of the sedative and the commencement of laryngoscopy. As such, we compared the effect of alfentanil and fentanyl on post-induction hemodynamic changes when administered as part of a standardized induction regimen including ketamine and rocuronium in ED RSI. METHODS: This was a double-blind pilot randomized controlled trial of adult patients requiring RSI in the ED of three urban Australian hospitals. Patients were randomized to receive either alfentanil or fentanyl in addition to ketamine and rocuronium for RSI. Non-invasive blood pressure and heart rate were measured immediately before and at two, four, and six minutes after induction. The primary outcome was the occurrence of at least one post-induction systolic blood pressure outside the pre-specified range of 100-160mmHg (with adjustment for patients with baseline hypertension). Secondary outcomes included hypertension, hypotension, hypoxia, first-pass intubation success, 30-day mortality, and the pattern of hemodynamic changes. RESULTS: A total of 61 patients were included in the final analysis (31 in the alfentanil group and 30 in the fentanyl group). The primary outcome was met in 58% of the alfentanil group and 50% of the fentanyl group (difference 8%, 95% confidence interval: -17% to 33%). The 30-day mortality rate, first-pass success rate, and incidences of hypertension, hypotension, and hypoxia were similar between the groups. There were no significant differences in systolic blood pressure or heart rate between the groups at any of the measured time-points. CONCLUSION: Alfentanil and fentanyl produced comparable post-induction hemodynamic changes when used as adjuncts to ketamine in ED RSI. Future studies could consider comparing different dosages of these opioids.

Factors Associated With Desaturation in Prehospital Rapid Sequence Intubation in a Helicopter Emergency Medical Service.

OBJECTIVE: Desaturation during prehospital rapid sequence intubation (RSI) is common and is associated with patient morbidity. Past studies have identified oxygen saturations at induction, the grade of laryngoscopy, and multiple attempts to intubate as being associated with desaturation. This study aimed to investigate whether there are other factors, identifiable before RSI, associated with desaturation. METHODS: This was a study of a physician-paramedic critical care team operating as Aeromedical Operations, NSW Ambulance. Prehospital RSIs (using paralysis) were studied retrospectively via patient case notes, monitor data, and an airway database. The review occurred between April 1, 2016, and December 31, 2018. Desaturation was defined as monitor recordings of saturations ≤ 92%. Logistic regression was performed for factors likely to be associated with desaturation. RESULTS: Desaturation occurred in 67 of 350 (19.1%) RSIs. Factors significantly associated with desaturation included male sex, a chest injury, increased weight, and lower saturations pre-RSI. CONCLUSION: Increased weight, chest injuries, and lower oxygen saturations are associated with desaturation at RSI. The variable male sex may be a surrogate for other as-yet unidentified factors.

Brain Injury Associated Shock: An Under-Recognized and Challenging Prehospital Phenomenon.

OBJECTIVE: Hemodynamic collapse in multi-trauma patients with severe traumatic brain injury (TBI) poses both a diagnostic and therapeutic challenge for prehospital clinicians. Brain injury associated shock (BIAS), likely resulting from catecholamine storm, can cause both ventricular dysfunction and vasoplegia but may present clinically in a manner similar to hemorrhagic shock. Despite different treatment strategies, few studies exist describing this phenomenon in the early post-injury phase. This retrospective observational study aimed to describe the frequency of shock in isolated TBI in prehospital trauma patients and to compare their clinical characteristics to those patients with hemorrhagic shock and TBI without shock. METHODS: All prehospital trauma patients intubated by prehospital medical teams from New South Wales Ambulance Aeromedical Operations (NSWA-AO) with an initial Glasgow Coma Scale (GCS) of 12 or less were investigated. Shock was defined as a pre-intubation systolic blood pressure under 90mmHg and the administration of blood products or vasopressors. Injuries were classified from in-hospital computed tomography (CT) reports. From this, three study groups were derived: BIAS, hemorrhagic shock, and isolated TBI without shock. Descriptive statistics were then produced for clinical and treatment variables. RESULTS: Of 1,292 intubated patients, 423 had an initial GCS of 12 or less, 24 patients (5.7% of the original cohort) had shock with an isolated TBI, and 39 patients had hemorrhagic shock. The hemodynamic parameters were similar amongst these groups, including values of tachycardia, hypotension, and elevated shock index. Prehospital clinical interventions including blood transfusion and total fluids administered were also similar, suggesting they were indistinguishable to prehospital clinicians. CONCLUSIONS: Hemodynamic compromise in the setting of isolated severe TBI is a rare clinical entity. Current prehospital physiological data available to clinicians do not allow for easy delineation between these patients from those with hemorrhagic shock.

Serratus Anterior Plane Blocks for Early Rib Fracture Pain Management: The SABRE Randomized Clinical Trial.

Importance: Rib fractures secondary to blunt thoracic trauma typically result in severe pain that is notoriously difficult to manage. The serratus anterior plane block (SAPB) is a regional anesthesia technique that provides analgesia to most of the hemithorax; however, SAPB has limited evidence for analgesic benefits in rib fractures. Objective: To determine whether the addition of an SAPB to protocolized care bundles increases the likelihood of early favorable analgesic outcomes and reduces opioid requirements in patients with rib fractures. Design, Setting, and Participants: This multicenter, open-label, pragmatic randomized clinical trial was conducted at 8 emergency departments across metropolitan and regional New South Wales, Australia, between April 12, 2021, and January 22, 2022. Patients aged 16 years or older with clinically suspected or radiologically proven rib fractures were included in the study. Participants were excluded if they were intubated, transferred for urgent surgical intervention, or had a major concomitant nonthoracic injury. Data were analyzed from September 2022 to July 2023. Interventions: Patients were randomly assigned (1:1) to receive an SAPB in addition to usual rib fracture management or standard care alone. Main Outcomes and Measures: The primary outcome was a composite pain score measured 4 hours after enrollment. Patients met the primary outcome if they had a pain score reduction of 2 or more points and an absolute pain score of less than 4 out of 10 points. Results: A total of 588 patients were screened, of whom 210 patients (median [IQR] age, 71 [55-84] years; 131 [62%] male) were enrolled, with 105 patients randomized to receive an SAPB plus standard care and 105 patients randomized to standard care alone. In the complete-case intention-to-treat primary outcome analysis, the composite pain score outcome was reached in 38 of 92 patients (41%) in the SAPB group and 18 of 92 patients (19.6%) in the control group (relative risk [RR], 0.73; 95% CI, 0.60-0.89; P = .001). There was a clinically significant reduction in overall opioid consumption in the SAPB group compared with the control group (eg, median [IQR] total opioid requirement at 24 hours: 45 [19-118] vs 91 [34-155] milligram morphine equivalents). Rates of pneumonia (6 patients [10%] vs 7 patients [11%]), length of stay (eg, median [IQR] hospital stay, 4.2 [2.2-7.7] vs 5 [3-7.3] days), and 30-day mortality (1 patient [1%] vs 3 patients [4%]) were similar between the SAPB and control groups. Conclusions and Relevance: This randomized clinical trial found that the addition of an SAPB to standard rib fracture care significantly increased the proportion of patients who experienced a meaningful reduction in their pain score while also reducing in-hospital opioid requirements. Trial Registration: http://anzctr.org.au Identifier: ACTRN12621000040864.

Mitochondrial Raf1 Regulates Glutamine Catabolism.

Raf kinases play vital roles in normal mitogenic signaling and cancer, however, the identities of functionally important Raf-proximal proteins throughout the cell are not fully known. Raf1 proximity proteomics/BioID in Raf1-dependent cancer cells unexpectedly identified Raf1-adjacent proteins known to reside in the mitochondrial matrix. Inner-mitochondrial localization of Raf1 was confirmed by mitochondrial purification and super-resolution microscopy. Inside mitochondria, Raf1 associated with glutaminase (GLS) in diverse human cancers and enabled glutaminolysis, an important source of biosynthetic precursors in cancer. These impacts required Raf1 kinase activity and were independent of canonical MAP kinase pathway signaling. Kinase-dead mitochondrial matrix-localized Raf1 impaired glutaminolysis and tumorigenesis in vivo. These data indicate that Raf1 localizes inside mitochondria where it interacts with GLS to engage glutamine catabolism and support tumorigenesis.

Optical, Structural, and Synchrotron X-ray Absorption Studies for GaN Thin Films Grown on Si by Molecular Beam Epitaxy.

GaN on Si plays an important role in the integration and promotion of GaN-based wide-gap materials with Si-based integrated circuits (IC) technology. A series of GaN film materials were grown on Si (111) substrate using a unique plasma assistant molecular beam epitaxy (PA-MBE) technology and investigated using multiple characterization techniques of Nomarski microscopy (NM), high-resolution X-ray diffraction (HR-XRD), variable angular spectroscopic ellipsometry (VASE), Raman scattering, photoluminescence (PL), and synchrotron radiation (SR) near-edge X-ray absorption fine structure (NEXAFS) spectroscopy. NM confirmed crack-free wurtzite (w-) GaN thin films in a large range of 180-1500 nm. XRD identified the w- single crystalline structure for these GaN films with the orientation along the c-axis in the normal growth direction. An optimized 700 °C growth temperature, plus other corresponding parameters, was obtained for the PA-MBE growth of GaN on Si, exhibiting strong PL emission, narrow/strong Raman phonon modes, XRD w-GaN peaks, and high crystalline perfection. VASE studies identified this set of MBE-grown GaN/Si as having very low Urbach energy of about 18 meV. UV (325 nm)-excited Raman spectra of GaN/Si samples exhibited the GaN E2(low) and E2(high) phonon modes clearly without Raman features from the Si substrate, overcoming the difficulties from visible (532 nm) Raman measurements with strong Si Raman features overwhelming the GaN signals. The combined UV excitation Raman-PL spectra revealed multiple LO phonons spread over the GaN fundamental band edge emission PL band due to the outgoing resonance effect. Calculation of the UV Raman spectra determined the carrier concentrations with excellent values. Angular-dependent NEXAFS on Ga K-edge revealed the significant anisotropy of the conduction band of w-GaN and identified the NEXAFS resonances corresponding to different final states in the hexagonal GaN films on Si. Comparative GaN material properties are investigated in depth.

Behavioural 'nudging' interventions to reduce low-value care for low back pain in the emergency department (NUDG-ED): protocol for a 2×2 factorial, before-after, cluster randomised trial.

INTRODUCTION: Opioids and imaging are considered low-value care for most people with low back pain. Yet around one in three people presenting to the emergency department (ED) will receive imaging, and two in three will receive an opioid. NUDG-ED aims to determine the effectiveness of two different behavioural 'nudge' interventions on low-value care for ED patients with low back pain. METHODS AND ANALYSIS: NUDG-ED is a 2×2 factorial, open-label, before-after, cluster randomised controlled trial. The trial includes 8 ED sites in Sydney, Australia. Participants will be ED clinicians who manage back pain, and patients who are 18 years or over presenting to ED with musculoskeletal back pain. EDs will be randomly assigned to receive (i) patient nudges, (ii) clinician nudges, (iii) both interventions or (iv) no nudge control. The primary outcome will be the proportion of encounters in ED for musculoskeletal back pain where a person received a non-indicated lumbar imaging test, an opioid at discharge or both. We will require 2416 encounters over a 9-month study period (3-month before period and 6-month after period) to detect an absolute difference of 10% in use of low-value care due to either nudge, with 80% power, alpha set at 0.05 and assuming an intra-class correlation coefficient of 0.10, and an intraperiod correlation of 0.09. Patient-reported outcome measures will be collected in a subsample of patients (n≥456) 1 week after their initial ED visit. To estimate effects, we will use a multilevel regression model, with a random effect for cluster and patient, a fixed effect indicating the group assignment of each cluster and a fixed effect of time. ETHICS AND DISSEMINATION: This study has ethical approval from Southwestern Sydney Local Health District Human Research Ethics Committee (2023/ETH00472). We will disseminate the results of this trial via media, presenting at conferences and scientific publications. TRIAL REGISTRATION NUMBER: ACTRN12623001000695.

Interleukin (IL)-1/IL-6-Inhibitor-Associated Drug Reaction With Eosinophilia and Systemic Symptoms (DReSS) in Systemic Inflammatory Illnesses.

BACKGROUND: After introducing IL-1/IL-6 inhibitors, some patients with Still and Still-like disease developed unusual, often fatal, pulmonary disease. This complication was associated with scoring as DReSS (drug reaction with eosinophilia and systemic symptoms) implicating these inhibitors, although DReSS can be difficult to recognize in the setting of systemic inflammatory disease. OBJECTIVE: To facilitate recognition of IL-1/IL-6 inhibitor-DReSS in systemic inflammatory illnesses (Still/Still-like) by looking at timing and reaction-associated features. We evaluated outcomes of stopping or not stopping IL-1/IL-6 inhibitors after DReSS reaction began. METHODS: In an international study collaborating primarily with pediatric specialists, we characterized features of 89 drug-reaction cases versus 773 drug-exposed controls and compared outcomes of 52 cases stopping IL-1/IL-6 inhibitors with 37 cases not stopping these drugs. RESULTS: Before the reaction began, drug-reaction cases and controls were clinically comparable, except for younger disease-onset age for reaction cases with preexisting cardiothoracic comorbidities. After the reaction began, increased rates of pulmonary complications and macrophage activation syndrome differentiated drug-reaction cases from drug-tolerant controls (P = 4.7 × 10-35 and P = 1.1 × 10-24, respectively). The initial DReSS feature was typically reported 2 to 8 weeks after initiating IL-1/IL-6 inhibition. In drug-reaction cases stopping versus not stopping IL-1/IL-6-inhibitor treatment, reaction-related features were indistinguishable, including pulmonary complication rates (75% [39 of 52] vs 76% [28 of 37]). Those stopping subsequently required fewer medications for treatment of systemic inflammation, had decreased rates of macrophage activation syndrome, and improved survival (P = .005, multivariate regression). Resolution of pulmonary complications occurred in 67% (26 of 39) of drug-reaction cases who stopped and in none who continued inhibitors. CONCLUSIONS: In systemic inflammatory illnesses, recognition of IL-1/IL-6-inhibitor-associated reactions followed by avoidance of IL-1/IL-6 inhibitors significantly improved outcomes.