Prehospital Tranexamic Acid for Severe Trauma.

BACKGROUND: Whether prehospital administration of tranexamic acid increases the likelihood of survival with a favorable functional outcome among patients with major trauma and suspected trauma-induced coagulopathy who are being treated in advanced trauma systems is uncertain. METHODS: We randomly assigned adults with major trauma who were at risk for trauma-induced coagulopathy to receive tranexamic acid (administered intravenously as a bolus dose of 1 g before hospital admission, followed by a 1-g infusion over a period of 8 hours after arrival at the hospital) or matched placebo. The primary outcome was survival with a favorable functional outcome at 6 months after injury, as assessed with the use of the Glasgow Outcome Scale-Extended (GOS-E). Levels on the GOS-E range from 1 (death) to 8 ("upper good recovery" [no injury-related problems]). We defined survival with a favorable functional outcome as a GOS-E level of 5 ("lower moderate disability") or higher. Secondary outcomes included death from any cause within 28 days and within 6 months after injury. RESULTS: A total of 1310 patients were recruited by 15 emergency medical services in Australia, New Zealand, and Germany. Of these patients, 661 were assigned to receive tranexamic acid, and 646 were assigned to receive placebo; the trial-group assignment was unknown for 3 patients. Survival with a favorable functional outcome at 6 months occurred in 307 of 572 patients (53.7%) in the tranexamic acid group and in 299 of 559 (53.5%) in the placebo group (risk ratio, 1.00; 95% confidence interval [CI], 0.90 to 1.12; P = 0.95). At 28 days after injury, 113 of 653 patients (17.3%) in the tranexamic acid group and 139 of 637 (21.8%) in the placebo group had died (risk ratio, 0.79; 95% CI, 0.63 to 0.99). By 6 months, 123 of 648 patients (19.0%) in the tranexamic acid group and 144 of 629 (22.9%) in the placebo group had died (risk ratio, 0.83; 95% CI, 0.67 to 1.03). The number of serious adverse events, including vascular occlusive events, did not differ meaningfully between the groups. CONCLUSIONS: Among adults with major trauma and suspected trauma-induced coagulopathy who were being treated in advanced trauma systems, prehospital administration of tranexamic acid followed by an infusion over 8 hours did not result in a greater number of patients surviving with a favorable functional outcome at 6 months than placebo. (Funded by the Australian National Health and Medical Research Council and others; PATCH-Trauma ClinicalTrials.gov number, NCT02187120.).

A randomized trial of expedited intra-arrest transfer versus more extended on-scene resuscitation for refractory out of hospital cardiac arrest: Rationale and design of the EVIDENCE trial.

BACKGROUND: Refractory Out of Hospital Cardiac Arrest (r-OHCA) is common and the benefit versus harm of intra-arrest transport of patients to hospital is not clear. OBJECTIVE: To assess the rate of survival to hospital discharge in adult patients with r-OHCA, initial rhythm pulseless ventricular tachycardia (VT)/ventricular fibrillation (VF) or Pulseless Electrical Activity (PEA) treated with 1 of 2 locally accepted standards of care:1 expedited transport from scene; or2 ongoing advanced life support (ALS) resuscitation on-scene. HYPOTHESIS: We hypothesize that expedited transport from scene in r-OHCA improves survival with favorable neurological status/outcome. METHODS/DESIGN: Phase III, multi-center, partially blinded, prospective, intention-to-treat, safety and efficacy clinical trial with contemporaneous registry of patient ineligible for the clinical trial. Eligible patients for inclusion are adults with witnessed r-OHCA; estimated age 18 to 70, assumed medical cause with immediate bystander cardiopulmonary resuscitation (CPR); initial rhythm of VF/pulseless VT, or PEA; no return of spontaneous circulation following 3 shocks and/or 15 minutes of professional on-scene resuscitation; with mechanical CPR available. Two hundred patients will be randomized in a 1:1 ratio to either expedited transport from scene or ongoing ALS at the scene of cardiac arrest. SETTING: Two urban regions in NSW Australia. OUTCOMES: Primary: survival to hospital discharge with cerebral performance category (CPC) 1 or 2. Secondary: safety, survival, prognostic factors, use of ECMO supported CPR and functional assessment at hospital discharge and 4 weeks and 6 months, quality of life, healthcare use and cost-effectiveness. CONCLUSIONS: The EVIDENCE trial will determine the potential risks and benefits of an expedited transport from scene of cardiac arrest.

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.

Triage Discordance in an Academic Pediatric Emergency Department and Disparities by Race, Ethnicity, and Language for Care.

BACKGROUND: Minoritized patients are disproportionately represented in low-acuity emergency department (ED) visits in the United States in part caused by lack of timely access to primary and urgent care. However, there is also the possibility that implicit bias during triage could contribute to disproportionate representation of minority groups in low-acuity ED visits. Triage discordance, defined as when ED resources used are different from initial triage score predictions, can be used as a proxy for triage accuracy. Recent data suggest that discordant triage may be common, although little is known about the interaction with race, ethnicity, and language for care. OBJECTIVES: This study aims to determine the prevalence of discordant triage among moderate- and low-acuity pediatric ED encounters and the interaction with patient race, ethnicity, and language for care. METHODS: We performed a retrospective analysis of pediatric ED encounters from 2019 with Emergency Severity Index (ESI) scores of 3, 4, or 5 at an academic referral hospital. The primary outcome was triage discordance, encompassing overtriage (ESI 3 and 4) and undertriage (ESI 4 and 5). Logistic and multinomial regressions were used to assess discordant triage by race, ethnicity, and language group. RESULTS: Triage discordance occurred in 47% (n = 18,040) of encounters. Black and Hispanic patients had higher likelihood of undertriage for ESI 5 (adjusted odds ratio 1.21, 95% confidence interval [CI] 1.01-1.46 and 1.27, 95% CI 1.07-1.52, respectively), and Black patients were more likely to be overtriaged in ESI 3 (1.18, 95% CI 1.09-1.27). Those with a language other than English for care had higher proportions of overtriage for ESI 3 (1.08, 95% CI 1.04-1.12) and undertriage for ESI 5 (1.23, 95% CI 1.11-1.37). CONCLUSIONS: We found high rates of triage discordance in our pediatric ED, with significant associations with race, ethnicity, and language for care. Future research should evaluate the source of triage discordance and develop quality improvement efforts to improve equitable care.

Cardiogenic Shock Challenges and Priorities: A Clinician Survey.

BACKGROUND: Cardiogenic shock (CS) is common and survival outcomes have not substantially improved. Australia's geography presents unique challenges in the management of CS. The challenges and research priorities for clinicians pertaining to CS identification and management have yet to be described. METHOD: We used an exploratory sequential mixed methods design. Semi-structured interviews were conducted with 10 clinicians (medical and nursing) to identify themes for quantitative evaluation. A total of 143 clinicians undertook quantitative evaluation through online survey. The interviews and surveys addressed current understanding of CS, status of cardiogenic systems and future research priorities. RESULTS: There were 143 respondents: 16 (11%) emergency, cardiology 22 (16%), 37 (26%) intensive care, 54 (38%) nursing. In total, 107 (75%) believe CS is under-recognised. Thirteen (13; 9%) of respondents indicated their hospital had existing CS teams, all from metropolitan hospitals, and 40% thought additional access to mechanical circulatory support devices was required. Five (5; 11%) non-tertiary hospital respondents had not experienced a delay in transfer of a patient in CS. All respondents felt additional research, particularly into the management of CS, was required. CONCLUSIONS: Clinicians report that CS is under-recognised and further research into CS management is required. Access to specialised CS services is still an issue and CS protocolised pathways may be of value.

DeepSWI: Using Deep Learning to Enhance Susceptibility Contrast on T2*-Weighted MRI.

BACKGROUND: Although susceptibility-weighted imaging (SWI) is the gold standard for visualizing cerebral microbleeds (CMBs) in the brain, the required phase data are not always available clinically. Having a postprocessing tool for generating SWI contrast from T2*-weighted magnitude images is therefore advantageous. PURPOSE: To create synthetic SWI images from clinical T2*-weighted magnitude images using deep learning and evaluate the resulting images in terms of similarity to conventional SWI images and ability to detect radiation-associated CMBs. STUDY TYPE: Retrospective. POPULATION: A total of 145 adults (87 males/58 females; 43.9 years old) with radiation-associated CMBs were used to train (16,093 patches/121 patients), validate (484 patches/4 patients), and test (2420 patches/20 patients) our networks. FIELD STRENGTH/SEQUENCE: 3D T2*-weighted, gradient-echo acquired at 3 T. ASSESSMENT: Structural similarity index (SSIM), peak signal-to-noise-ratio (PSNR), normalized mean-squared-error (nMSE), CMB counts, and line profiles were compared among magnitude, original SWI, and synthetic SWI images. Three blinded raters (J.E.V.M., M.A.M., B.B. with 8-, 6-, and 4-years of experience, respectively) independently rated and classified test-set images. STATISTICAL TESTS: Kruskall-Wallis and Wilcoxon signed-rank tests were used to compare SSIM, PSNR, nMSE, and CMB counts among magnitude, original SWI, and predicted synthetic SWI images. Intraclass correlation assessed interrater variability. P values <0.005 were considered statistically significant. RESULTS: SSIM values of the predicted vs. original SWI (0.972, 0.995, 0.9864) were statistically significantly higher than that of the magnitude vs. original SWI (0.970, 0.994, 0.9861) for whole brain, vascular structures, and brain tissue regions, respectively; 67% (19/28) CMBs detected on original SWI images were also detected on the predicted SWI, whereas only 10 (36%) were detected on magnitude images. Overall image quality was similar between the synthetic and original SWI images, with less artifacts on the former. CONCLUSIONS: This study demonstrated that deep learning can increase the susceptibility contrast present in neurovasculature and CMBs on T2*-weighted magnitude images, without residual susceptibility-induced artifacts. This may be useful for more accurately estimating CMB burden from magnitude images alone. EVIDENCE LEVEL: 3. TECHNICAL EFFICACY: Stage 2.

Concurrently mapping quantitative trait loci associations from multiple subspecies within hybrid populations.

Many of the world's agriculturally important plant and animal populations consist of hybrids of subspecies. Cattle in tropical and sub-tropical regions for example, originate from two subspecies, Bos taurus indicus (Bos indicus) and Bos taurus taurus (Bos taurus). Methods to derive the underlying genetic architecture for these two subspecies are essential to develop accurate genomic predictions in these hybrid populations. We propose a novel method to achieve this. First, we use haplotypes to assign SNP alleles to ancestral subspecies of origin in a multi-breed and multi-subspecies population. Then we use a BayesR framework to allow SNP alleles originating from the different subspecies differing effects. Applying this method in a composite population of B. indicus and B. taurus hybrids, our results show that there are underlying genomic differences between the two subspecies, and these effects are not identified in multi-breed genomic evaluations that do not account for subspecies of origin effects. The method slightly improved the accuracy of genomic prediction. More significantly, by allocating SNP alleles to ancestral subspecies of origin, we were able to identify four SNP with high posterior probabilities of inclusion that have not been previously associated with cattle fertility and were close to genes associated with fertility in other species. These results show that haplotypes can be used to trace subspecies of origin through the genome of this hybrid population and, in conjunction with our novel Bayesian analysis, subspecies SNP allele allocation can be used to increase the accuracy of QTL association mapping in genetically diverse populations.

Toward Improving Patient Equity in a Pediatric Emergency Department: A Framework for Implementation.

Disparities in health care delivery and health outcomes for patients in the emergency department (ED) by race, ethnicity, and language for care (REaL) are common and well documented. Addressing inequities from structural racism, implicit bias, and language barriers can be challenging, and there is a lack of data on effective interventions. We describe the implementation of a multifaceted equity improvement strategy in a pediatric ED using Kotter's model for change as a framework to identify the key drivers. The main elements included a data dashboard with quality metrics stratified by patient self-reported REaL to visualize disparities, a staff workshop on implicit bias and microaggressions, and several clinical and operational tools that highlight equity. Our next steps include refining and repeating interventions and tracking important patient outcomes, including timely pain treatment, triage assessment, diagnostic evaluations, and interpreter use, with the overall goal of improving patient equity by REaL over time. This article presents a roadmap for a disparity reduction intervention, which can be part of a multifaceted approach to address health equity in EDs.

Intentions and willingness to engage in risky driving behaviour among high school adolescents: evaluating the bstreetsmart road safety programme.

OBJECTIVE: To investigate the impact of a road safety programme on adolescents' willingness to engage in risky behaviour as probationary drivers, adjusted for covariates of interest. METHOD: The bstreetsmart is a road safety programme delivered to around 25 000 adolescent students annually in New South Wales. Using a smartphone-based app, student and teacher participation incentives, students were surveyed before and after programme attendance. Mixed-methods linear regression analysed pre/post-modified Behaviour of Young Novice Driver (BYNDS_M) scores. RESULTS: 2360 and 1260 students completed pre-event and post-event surveys, respectively. Post-event BYNDS_M scores were around three points lower than pre-event scores (-2.99, 95% CI -3.418 to -2.466), indicating reduced intention to engage in risky driving behaviours. Covariates associated with higher stated intentions of risky driving were exposure to risky driving as a passenger (1.21, 95% CI 0.622 to 2.011) and identifying as non-binary gender (2.48, 95% CI 1.879 to 4.085), adjusting for other predictors. CONCLUSIONS: Trauma-informed, reality-based injury prevention programmes can be effective in changing short-term stated intentions to engage in risky driving, among a pre-independent driving student population. The adolescent novice driver age group is historically challenging to engage, and injury prevention action must be multipronged to address the many factors influencing their behaviour.

Prehospital Ultrasound-Guided Pediatric Fascia Iliaca Block.

The fascia iliaca block (FIB) provides effective regional anesthesia for fractures of the femur. There is 1 previous case report of a prehospital FIB in a child using a landmark technique. We report the successful prehospital application of a FIB using ultrasound guidance in a 7-year-old girl.

A multicenter evaluation of the accuracy of prehospital eFAST by a physician-staffed helicopter emergency medical service.

PURPOSE: The purpose of this study is to report the relative accuracy of prehospital extended focused assessment with sonography in trauma (eFAST) examinations performed by HEMS physicians. METHODS: Trauma patients who received prehospital eFAST by HEMS clinicians between January 2013 and December 2017 were reviewed. The clinician's interpretations of these ultrasounds were compared to gold standard references of CT imaging or operating room findings. The outcomes measured include the calculated accuracy of eFAST for detecting intraperitoneal free fluid (IPFF), pneumothorax, hemothorax, and pericardial fluid compared to available gold standard results. RESULTS: Of the 411 patients with adequate data for comparison, the median age was 39.5 years with 73% male and 98% sustaining blunt force trauma. For the detection of IPFF, eFAST had a sensitivity of 25% (95% CI 16-36%) and specificity of 96% (95% CI 93-98%). Sensitivities and specificities were calculated for pneumothorax (38% and 96% respectively), hemothorax (17% and 97% respectively), and pericardial effusion (17% and 100% respectively). These results did not change significantly when reassessed with several sensitivity analyses. CONCLUSION: Prehospital eFAST is reliable for detecting the presence of intraperitoneal free fluid. This finding should inform receiving trauma teams to prepare for early definitive care in these patients. The low sensitivities across all components of the eFAST highlight the importance of cautiously interpreting negative studies while prompting the need for further studies. TRIAL REGISTRATION: ACTRN12618001973202 (Registered on 06/12/2018).

Simultaneous multi-slice spin- and gradient-echo dynamic susceptibility-contrast perfusion-weighted MRI of gliomas.

Although combined spin- and gradient-echo (SAGE) dynamic susceptibility-contrast (DSC) MRI can provide perfusion quantification that is sensitive to both macrovessels and microvessels while correcting for T1 -shortening effects, spatial coverage is often limited in order to maintain a high temporal resolution for DSC quantification. In this work, we combined a SAGE echo-planar imaging (EPI) sequence with simultaneous multi-slice (SMS) excitation and blipped controlled aliasing in parallel imaging (blipped CAIPI) at 3 T to achieve both high temporal resolution and whole brain coverage. Two protocols using this sequence with multi-band (MB) acceleration factors of 2 and 3 were evaluated in 20 patients with treated gliomas to determine the optimal scan parameters for clinical use. ΔR2 *(t) and ΔR2 (t) curves were derived to calculate dynamic signal-to-noise ratio (dSNR), ΔR2 *- and ΔR2 -based relative cerebral blood volume (rCBV), and mean vessel diameter (mVD) for each voxel. The resulting SAGE DSC images acquired using MB acceleration of 3 versus 2 appeared visually similar in terms of image distortion and contrast. The difference in the mean dSNR from normal-appearing white matter (NAWM) and that in the mean dSNR between NAWM and normal-appearing gray matter were not statistically significant between the two protocols. ΔR2 *- and ΔR2 -rCBV maps and mVD maps provided unique contrast and spatial heterogeneity within tumors.

Retrieval transfusion protocol in New South Wales, Australia: A retrospective review of the first 5 years.

BACKGROUND: Ambulance service blood transfusion is an area of rapid development. In New South Wales, Australia, the blood products carried by ambulance medical teams are often the first available to patients with critical bleeding. In addition to the blood products routinely carried by these teams, the Service created and implemented a method of initiating large-volume, mixed-product transfusions using existing blood banks: the Retrieval Transfusion Procedure (RTP). This article describes the trends and characteristics of New South Wales Ambulance RTP activations. MATERIALS AND METHODS: This retrospective database review examines the patient records for all RTP activations. Key areas of investigation include logistics, product requests, population demographics, etiologies, physiology, mission timings, and transfusions. RESULTS: Ambulance medical teams attended 27 531 missions in the reviewed period, 1573 patients received transfusion, and there were 138 RTP activations. Blood products were sourced from 40 banks and transported by police (46.7%), ambulance (27.1%), and helicopter (13.0%) to refueling stops (39.2%), prehospital scenes (24.2%) and hospitals (15.8%). The median time engaged on each mission was 189 minutes for metropolitan and 222 minutes for rural locations. Seventy-eight patients were transfused with RTP blood products; 83.3% were traumas, of which 63.1% were motor vehicle collisions. Up to 18 units of blood products were administered before hospital arrival. There was significant (P < .001) improvement in the mean shock index of transfused patients between the first and final observations recorded. CONCLUSIONS: Ambulance service extended blood product transfusion is logistically achievable and facilitates emergency transfusions throughout the state with minimal additional infrastructure.

Prehospital Blood Transfusion in New South Wales, Australia: A Retrospective Cohort Study.

INTRODUCTION: Catastrophic hemorrhage remains the leading cause of preventable death. Not all New South Wales (NSW) hospitals stock blood products and, as such, blood products carried by NSW Ambulance retrieval teams are often the first available to critically unwell patients. OBJECTIVE: To describe the trends, characteristics and predictors of mortality prior to hospital treatment in patients receiving prehospital blood transfusion by NSW Ambulance retrieval teams attending primary missions from 2009-2018. METHODS: Retrospective review of all patients who received blood products with NSW Ambulance retrieval teams between 13/8/2009 and 31/12/2018. RESULTS: A total of 12,468 primary taskings were reviewed, identifying 1,043 (8.4%) cases of prehospital transfusion. The proportion of missions administering blood transfusions doubled between 2009 and 2018. Road traffic incidents were the predominant etiology. Eighty per cent of patients (n = 842) reached hospital alive following transfusion. Retrieval missions had a median time of 117 minutes (IQR 74-168). An initial blood pressure <100mmHg and reduced GCS were strongly associated with prehospital mortality. The median shock index of patients prior to transfusion was 1.2, which reduced to 1.0 after transfusion. CONCLUSION: The use of prehospital blood transfusion for suspected bleeding in NSW Australia has more than doubled since 2010. Patients who received prehospital transfusion arrived at hospital with improved hemodynamic observations.

Three-dimensional inhomogeneous magnetization transfer with rapid gradient-echo (3D ihMTRAGE) imaging.

PURPOSE: To demonstrate the feasibility of integrating the magnetization transfer (MT) preparations required for inhomogeneous MT (ihMT) within an MPRAGE-style acquisition. Such a sequence allows for reduced power deposition and easy inclusion of other modules. METHODS: An ihMT MPRAGE-style sequence (ihMTRAGE) was initially simulated to investigate acquisition of the 3D ihMT data sequentially, or in an interleaved manner. The ihMTRAGE sequence was implemented on a 3T clinical scanner to acquire ihMT data from the brain and spine. RESULTS: Both simulations and in vivo data provided an ihMT signal that was significantly greater using a sequential ihMTRAGE acquisition, compared with an interleaved implementation. Comparison with a steady-state ihMT acquisition (defined as having one MT RF pulse between successive acquisition modules) demonstrated how ihMTRAGE allows for a reduction in average power deposition, or greater ihMT signal at equal average power deposition. Inclusion of a prospective motion-correction module did not significantly affect the ihMT signal obtained from regions of interest in the brain. The ihMTRAGE acquisition allowed combination with a spatial saturation module to reduce phase wrap artifacts in a cervical spinal cord acquisition. CONCLUSIONS: Use of preparations necessary for ihMT experiments within an MPRAGE-style sequence provides a useful alternative for acquiring 3D ihMT data. Compared with our steady-state implementation, ihMTRAGE provided reduced power deposition, while allowing use of the maximum intensity from off-resonance RF pulses. The 3D ihMTRAGE acquisition allowed combination of other modules with the preparation necessary for ihMT experiments, specifically motion compensation and spatial saturation modules.

A within-coil optical prospective motion-correction system for brain imaging at 7T.

PURPOSE: Motion artifact limits the clinical translation of high-field MR. We present an optical prospective motion correction system for 7 Tesla MRI using a custom-built, within-coil camera to track an optical marker mounted on a subject. METHODS: The camera was constructed to fit between the transmit-receive coils with direct line of sight to a forehead-mounted marker, improving upon prior mouthpiece work at 7 Tesla MRI. We validated the system by acquiring a 3D-IR-FSPGR on a phantom with deliberate motion applied. The same 3D-IR-FSPGR and a 2D gradient echo were then acquired on 7 volunteers, with/without deliberate motion and with/without motion correction. Three neuroradiologists blindly assessed image quality. In 1 subject, an ultrahigh-resolution 2D gradient echo with 4 averages was acquired with motion correction. Four single-average acquisitions were then acquired serially, with the subject allowed to move between acquisitions. A fifth single-average 2D gradient echo was acquired following subject removal and reentry. RESULTS: In both the phantom and human subjects, deliberate and involuntary motion were well corrected. Despite marked levels of motion, high-quality images were produced without spurious artifacts. The quantitative ratings confirmed significant improvements in image quality in the absence and presence of deliberate motion across both acquisitions (P < .001). The system enabled ultrahigh-resolution visualization of the hippocampus during a long scan and robust alignment of serially acquired scans with interspersed movement. CONCLUSION: We demonstrate the use of a within-coil camera to perform optical prospective motion correction and ultrahigh-resolution imaging at 7 Tesla MRI. The setup does not require a mouthpiece, which could improve accessibility of motion correction during 7 Tesla MRI exams.

Use of whole-genome sequence data and novel genomic selection strategies to improve selection for age at puberty in tropically-adapted beef heifers.

BACKGROUND: In tropically-adapted beef heifers, application of genomic prediction for age at puberty has been limited due to low prediction accuracies. Our aim was to investigate novel methods of pre-selecting whole-genome sequence (WGS) variants and alternative analysis methodologies; including genomic best linear unbiased prediction (GBLUP) with multiple genomic relationship matrices (MGRM) and Bayesian (BayesR) analyses, to determine if prediction accuracy for age at puberty can be improved. METHODS: Genotypes and phenotypes were obtained from two research herds. In total, 868 Brahman and 960 Tropical Composite heifers were recorded in the first population and 3695 Brahman, Santa Gertrudis and Droughtmaster heifers were recorded in the second population. Genotypes were imputed to 23 million whole-genome sequence variants. Eight strategies were used to pre-select variants from genome-wide association study (GWAS) results using conditional or joint (COJO) analyses. Pre-selected variants were included in three models, GBLUP with a single genomic relationship matrix (SGRM), GBLUP MGRM and BayesR. Five-way cross-validation was used to test the effect of marker panel density (6 K, 50 K and 800 K), analysis model, and inclusion of pre-selected WGS variants on prediction accuracy. RESULTS: In all tested scenarios, prediction accuracies for age at puberty were highest in BayesR analyses. The addition of pre-selected WGS variants had little effect on the accuracy of prediction when BayesR was used. The inclusion of WGS variants that were pre-selected using a meta-analysis with COJO analyses by chromosome, fitted in a MGRM model, had the highest prediction accuracies in the GBLUP analyses, regardless of marker density. When the low-density (6 K) panel was used, the prediction accuracy of GBLUP was equal (0.42) to that with the high-density panel when only six additional sequence variants (identified using meta-analysis COJO by chromosome) were included. CONCLUSIONS: While BayesR consistently outperforms other methods in terms of prediction accuracies, reasonable improvements in accuracy can be achieved when using GBLUP and low-density panels with the inclusion of a relatively small number of highly relevant WGS variants.

FentAnyl or placebo with KeTamine for emergency department rapid sequence intubation: The FAKT study protocol.

BACKGROUND: Some critically ill patients require rapid sequence intubation in the emergency department, and ketamine is one sedative agent employed, due to its relative haemodynamic stability. Tachycardia and hypertension are frequent side effects, and in less stable patients, shock can be unmasked or exacerbated. The use of fentanyl as a co-induction agent may lead to a smoother haemodynamic profile post-induction, which may lead to reduced mortality in this critically ill cohort. This randomised controlled trial aims to compare the effect of administering fentanyl vs placebo in a standardised induction regimen with ketamine and rocuronium on (a) the percentage of patients in each group with a systolic blood pressure outside the range of 100-150 mm Hg within 10 minutes of induction, (b) the laryngoscopic view, and (c) 30-day mortality. METHODS/DESIGN: Three hundred patients requiring rapid sequence intubation in participating emergency departments will be randomised to receive either fentanyl or placebo (0.9% saline) in addition to ketamine and rocuronium according to a standardised, weight-based induction regimen. The primary outcome measure is the percentage of patients in each group with a systolic blood pressure outside the range of 100-150 mm Hg within 10 minutes of induction. Secondary outcome measures include the laryngoscopic view, percentage of first pass success, 30-day mortality and number of ventilator-free days at 30 days. DISCUSSION: The effect of adding fentanyl to an induction regimen of ketamine and rocuronium will be evaluated, both in terms of post-intubation physiology, the effect on intubating conditions, and 30-day mortality.

Long-term Effectiveness of the Airway Registry at Sydney Helicopter Emergency Medical Service.

OBJECTIVE: Prehospital rapid sequence intubation (RSI) is prone to suboptimal documentation. The Greater Sydney Area Helicopter Emergency Medical Service (GSA-HEMS) uses a dedicated Airway Registry (AR) to aid documentation. The AR was only evaluated shortly after its introduction. This first evaluation is followed up to assess the long-term effectiveness of the AR. The secondary objective was to compare the AR with templates in the literature. METHODS: A retrospective review of electronic records was undertaken to compare completeness of documentation between an immediate postintroduction and a long-term postintroduction cohort. Differences between the two cohorts were tested for significance. RESULTS: There was no significant difference in documentation for Cormack-Lehane laryngoscopy grade at the first intubation attempt (P = .552) and confirmation of end-tidal carbon dioxide (P = .258). A significant improvement in the documentation of laryngoscopy grade for the second attempt (P = 0) was found. The documentation of intubator details remained at 100% (165/165). The variables collected by GSA-HEMS corresponded well to the literature, but some definitions differ (eg, desaturation). CONCLUSION: There was no significant change in completeness of documentation for most key intubation variables eight years after the introduction of the AR. GSA-HEMS performs well in registering variables as proposed in the literature; however, variable definitions need to be synchronized.

Fast dynamic ventilation MRI of hyperpolarized 129 Xe using spiral imaging.

PURPOSE: To develop and optimize a rapid dynamic hyperpolarized 129 Xe ventilation (DXeV) MRI protocol and investigate the feasibility of capturing pulmonary signal-time curves in human lungs. THEORY AND METHODS: Spiral k-space trajectories were designed with the number of interleaves Nint = 1, 2, 4, and 8 corresponding to voxel sizes of 8 mm, 5 mm, 4 mm, and 2.5 mm, respectively, for field of view = 15 cm. DXeV images were acquired from a gas-flow phantom to investigate the ability of Nint = 1, 2, 4, and 8 to capture signal-time curves. A finite element model was constructed to investigate gas-flow dynamics corroborating the experimental signal-time curves. DXeV images were also carried out in six subjects (three healthy and three chronic obstructive pulmonary disease subjects). RESULTS: DXeV images and numerical modelling of signal-time curves permitted the quantification of temporal and spatial resolutions for different numbers of spiral interleaves. The two-interleaved spiral (Nint = 2) was found to be the most time-efficient to obtain DXeV images and signal-time curves of whole lungs with a temporal resolution of 624 ms for 13 slices. Signal-time curves were well matched in three healthy volunteers. The Spearman's correlations of chronic obstructive pulmonary disease subjects were statistically different from three healthy subjects (P < 0.05). CONCLUSION: The Nint = 2 spiral demonstrates the successful acquisition of DXeV images and signal-time curves in healthy subjects and chronic obstructive pulmonary disease patients. Magn Reson Med 79:2597-2606, 2018. © 2017 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.