An ALK2 inhibitor, BLU-782, prevents heterotopic ossification in a mouse model of fibrodysplasia ossificans progressiva.

Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disease driven by gain-of-function variants in activin receptor-like kinase 2 (ALK2), the most common variant being ALK2R206H. In FOP, ALK2 variants display increased and dysregulated signaling through the bone morphogenetic protein (BMP) pathway resulting in progressive and permanent replacement of skeletal muscle and connective tissues with heterotopic bone, ultimately leading to severe debilitation and premature death. Here, we describe the discovery of BLU-782 (IPN60130), a small-molecule ALK2R206H inhibitor developed for the treatment of FOP. A small-molecule library was screened in a biochemical ALK2 binding assay to identify potent ALK2 binding compounds. Iterative rounds of structure-guided drug design were used to optimize compounds for ALK2R206H binding, ALK2 selectivity, and other desirable pharmacokinetic properties. BLU-782 preferentially bound to ALK2R206H with high affinity, inhibiting signaling from ALK2R206H and other rare FOP variants in cells in vitro without affecting signaling of closely related homologs ALK1, ALK3, and ALK6. In vivo efficacy of BLU-782 was demonstrated using a conditional knock-in ALK2R206H mouse model, where prophylactic oral dosing reduced edema and prevented cartilage and heterotopic ossification (HO) in both muscle and bone injury models. BLU-782 treatment preserved the normal muscle-healing response in ALK2R206H mice. Delayed dosing revealed a short 2-day window after injury when BLU-782 treatment prevented HO in ALK2R206H mice, but dosing delays of 4 days or longer abrogated HO prevention. Together, these data suggest that BLU-782 may be a candidate for prevention of HO in FOP.

Bed tilt and ramp positions are associated with increased first-pass success of adult endotracheal intubation in the emergency department: A registry study.

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.

Comparison of supine and upright face-to-face cadaver intubation.

INTRODUCTION: Optimal patient positioning during intubation improves laryngeal view and first pass success, as well as reducing incidence of hypoxia. In certain pre-hospital situations, it may be impractical or impossible for the operator to stand behind the patient. OBJECTIVE: We compared intubation in the supine and upright face-to-face positions, with regards to time to intubate and the view of the vocal cords obtained. METHODS: This was a pilot comparison study. One investigator intubated 25 cadavers with the use of a bougie in the supine and upright face-to-face positions. Each attempt was recorded on a video laryngoscope. Recordings of each attempt were reviewed by five blinded emergency physicians, who allocated both a percentage of glottic opening (POGO) score and Cormack-Lehane (CL) grade. Time to insertion of the endotracheal tube (ETT) through the vocal cords was measured from the video. RESULTS: The median intubation time was 1 s longer for upright cadavers than for supine cadavers, with greater variation in intubation times for upright cadavers compared with supine cadavers (IQR 9.0 vs 3.5 excluding the outlier case). The mean POGO score (averaged across raters) was 4.7% lower for upright intubation attempts (excluding the outlier case) with a moderate-to-good degree of inter-rater reliability, however this difference was not statistically significant. The median CL grade (averaged across raters) was 0.2 higher for upright intubation attempts (excluding the outlier case) with a poor-to-moderate degree of inter-rater reliability, and this difference was also not statistically significant. CONCLUSIONS: This pilot study suggests that upright, face-to-face intubation may be clinically similar to supine intubation in terms of time to intubation and difficulty. Further studies utilising a larger number of operators and cadaver types are indicated.

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.

Apnoeic oxygenation was associated with decreased desaturation rates during rapid sequence intubation in multiple Australian and New Zealand emergency departments.

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.

A sequential case series of 23 intubations in a rural emergency department in New Zealand.

OBJECTIVE: To describe the practice and procedure of emergency intubation in Whanganui Emergency Department, New Zealand and determine whether intubation can be carried out effectively in the rural setting. METHOD: A prospective observational study using the Australia and New Zealand Airway Registry proforma to collect data on the indication, lead intubator, first-pass success rate and peri-procedural complications. Data were also collected on whether a formal airway assessment was carried out and whether a checklist was used. RESULTS: Twenty-three patients were intubated in the emergency department over a 12-month period. Sixty-two percent (14/23 cases) were medical encounters and the remaining 38% of indications due to a trauma. Head injury was the most common indication (23%). Ninety-two percent of primary intubators were emergency department-based Fellowship of the Australasian College for Emergency Medicine or resident medical officers, while anaesthetic-trained operators accounted for just 8%. Our first-pass intubation success rate was 87% and 16% of cases had procedural complications. Sixty-five percent (15/23) carried out a formal airway assessment and a checklist was only used in 23% of cases. CONCLUSION: This sequential case series is the first study looking at airway management in rural New Zealand emergency department airway practice. Overall intubation success rates were comparable to larger tertiary centres across Australasia. We have demonstrated that with adequate resources and adherence to interventions, a rural emergency department can provide effective airway management.

Emergency airway management in Australian and New Zealand emergency departments: A multicentre descriptive study of 3710 emergency intubations.

OBJECTIVE: The aim of this study was to describe the practice of endotracheal intubation across a range of Australasian EDs. METHODS: We established a multicentre airway registry (The Australian and New Zealand Emergency Department Airway Registry [ANZEDAR]) prospectively capturing intubations from 43 Australian and New Zealand EDs over 24 months using the ANZEDAR form. Information recorded included patient demographics, intubation indications, predicted difficulty, rapid sequence induction and endotracheal intubation preparation technique, induction drugs, airway adjuncts and complications. Factors associated with first attempt success were explored. RESULTS: Of the 3710 intubations captured, 3533 were in adults (95.2%), 2835 (76.4%) for medical and 810 (21.8%) for trauma indications. Overall, 3127 (84.3%) patients were successfully intubated at the first attempt; the majority by ED doctors (2654 [72.1%]). A total of 10 surgical airways were performed, all of which were successful cricothyroidotomies. Propofol, thiopentone or ketamine were used with similar frequency for induction, and suxamethonium was the most often used muscle relaxant. Adverse events were reported in 964 (26%), the majority involving desaturation or hypotension. CONCLUSION: Australasian ED doctors, predominantly specialist emergency physicians or trainees, perform the majority of ED intubations using rapid sequence induction as their preferred technique mainly for medical indications. First attempt success rate was not different between different types of EDs, and is comparable published international data. Complications are not infrequent, and are comparable to other published series. Monitoring and reporting of ED intubation practice will enable continued improvements in the safety of this high-risk procedure.

The Royal North Shore Hospital Emergency Department airway registry: Closing the audit loop.

OBJECTIVE: We aim to investigate whether a bundle of changes made to the practice of endotracheal intubation in our ED was associated with an improvement in first pass success rate and a reduction in the incidence of complications. METHODS: We used a prospective observational study. RESULTS: The data on 360 patients who were intubated during an 18-month period following the introduction of these changes were compared with our previously published observational data. Success on first attempt at intubation improved 83.4% to 93.9% (P < 0.0001). The proportion of patients with one or more complication fell from 29.0% to 19.4% (P < 0.042). Oesophageal intubation fell from 4.0% to 0.3% (P < 0.001), and there was a non-significant reduction in the rate of desaturation, from 15.6% to 10.9% (P < 0.07). CONCLUSION: We have shown that, through the introduction of a bundle of changes that spans the domains of staff training, equipment and practice standardisation, we have made significant improvements in the safety of patients undergoing endotracheal intubation in our ED.

Comparison of the C-MAC video laryngoscope with direct Macintosh laryngoscopy in the emergency department.

OBJECTIVE: To investigate the first pass success rate, airway grade and complications in two tertiary EDs with the C-MAC video laryngoscope (VL), when compared with standard direct laryngoscopy (DL). METHODS: This was a retrospective analysis of prospectively collected data entered into an airway registry database in the EDs of Royal North Shore and St George Hospitals (SGH) over a 30 month period. Doctors had the choice of using either DL using a Macintosh or Miller blade or a C-MAC VL for the intubation. RESULTS: Six hundred and nineteen consecutive patients were recruited. There was no statistical difference between VL and DL in grade of view obtained, P = 0.526. Chance of intubation success increased by more than threefold by using a C-MAC VL in the setting of a grade III/IV (total of 109) on DL (OR = 3.06; 95% CI: 1.52-6.17; P = 0.002). CONCLUSION: This is the first observational study of airway management comparing the C-MAC VL with DL blades in an Australian ED population. Our findings revealed that although the C-MAC VL overall did not provide an enhanced view of the larynx over the Macintosh DL, it was superior to DL when the grade was at least grade III. Currently we are unable to reliably predict the grade by any algorithm prior to intubation. Findings from this study suggest that the C-MAC VL should be considered as the first line laryngoscope in all ED intubations not just the ones predicted to be difficult.

Identifying incidents of suboptimal care during paediatric emergencies-an observational study utilising in situ and simulation centre scenarios.

AIM: Life threatening paediatric emergencies are relatively uncommon events. When they do occur staff caring for these children must have the ability to recognise the deterioration, evaluate and simultaneously treat these patients. The aim of this study was to identify suboptimal care during standardised simulated scenarios and to identify the potential causation factors. METHODS: Participants were emergency department and operating theatre staff in Sydney, Australia. Incidents of suboptimal care were identified during scenarios and were analysed by thematic qualitative assessment methods. Potential causation factors were elicited both during and immediately after the scenarios and during facilitated debriefings. Causation factors were attributed to any of seven pre-defined categories. RESULTS: Seventy-three simulations occurred over 9 month period in 2011. 270 doctors, 235 nurses and 11 students participated. 194 incidents of suboptimal care were observed and attributed to 325 causation factors. There were 76 knowledge deficits, 39 clinical skill deficits, 36 leadership problems, 84 communication failures, 20 poor resource utilisations, 23 preparation and planning failures and 47 incidents of a loss of situational awareness. Clinically important themes were: paediatric life support, drug choice and doses, advanced airway and ventilation, intravenous fluids and recognition of the deteriorating patient. Recurring incidents included the failure to recognise a cardiac arrest, inadequate fluid resuscitation and incorrect medication dose administration. CONCLUSIONS: During standardised paediatric simulations multiple incidents of suboptimal care have been identified and multiple causation factors attributed to these. Educators should use this information to adapt current training programs to encompass these factors.

Contextual information influences diagnosis accuracy and decision making in simulated emergency medicine emergencies.

BACKGROUND: It is well documented that adaptations in cognitive processes with increasing skill levels support decision making in multiple domains. We examined skill-based differences in cognitive processes in emergency medicine physicians, and whether performance was significantly influenced by the removal of contextual information related to a patient's medical history. METHOD: Skilled (n=9) and less skilled (n=9) emergency medicine physicians responded to high-fidelity simulated scenarios under high- and low-context information conditions. RESULTS: Skilled physicians demonstrated higher diagnostic accuracy irrespective of condition, and were less affected by the removal of context-specific information compared with less skilled physicians. The skilled physicians generated more options, and selected better quality options during diagnostic reasoning compared with less skilled counterparts. These cognitive processes were active irrespective of the level of context-specific information presented, although high-context information enhanced understanding of the patients' symptoms resulting in higher diagnostic accuracy. CONCLUSIONS: Our findings have implications for scenario design and the manipulation of contextual information during simulation training.

Prospective observational study of the practice of endotracheal intubation in the emergency department of a tertiary hospital in Sydney, Australia.

OBJECTIVE: To describe the practice of endotracheal intubation in the ED of a tertiary hospital in Australia, with particular emphasis on the indication, staff seniority, technique, number of attempts required and the rate of complications. METHODS: A prospective observational study. RESULTS: Two hundred and ninety-five intubations occurred in 18 months. Trauma was the indication for intubation in 30.5% (95% CI 25.3-36.0) and medical conditions in 69.5% (95% CI 64.0-74.5). Emergency physicians were team leaders in 69.5% (95% CI 64.0-74.5), whereas ED registrars or senior Resident Medical Officers made the first attempt at intubation in 88.1% (95% CI 83.9-91.3). Difficult laryngoscopy occurred in 24.0% (95% CI 19.5-29.3) of first attempts, whereas first pass success occurred in 83.4% (95% CI 78.7-87.2). A difficult intubation occurred in 3.4% (95% CI 1.9-6.1) and all patients were intubated orally in five or less attempts. A bougie was used in 30.9% (95% CI 25.8-36.5) of first attempts, whereas a stylet in 37.5% (95% CI 32.1-43.3). Complications occurred in 29.0% (95% CI 23.5-34.1) of the patients, with desaturation the commonest in 15.7% (95% CI 11.9-20.5). Cardiac arrest occurred in 2.2% (95% CI 0.9-4.4) after intubation. No surgical airways were undertaken. CONCLUSION: Although the majority of results are comparable with overseas data, the rates of difficult laryngoscopy and desaturation are higher than previously reported. We feel that this data has highlighted the need for practice improvement within our department and we would encourage all those who undertake emergent airway management to audit their own practice of this high-risk procedure.

Calcium mediates glomerular filtration through calcineurin and mTORC2/Akt signaling.

Alterations to the structure of the glomerular filtration barrier lead to effacement of podocyte foot processes, leakage of albumin, and the development of proteinuria. To better understand the signaling pathways involved in the response of the glomerular filtration barrier to injury, we studied freshly isolated rat glomeruli, which allows for the monitoring and pharmacologic manipulation of early signaling events. Administration of protamine sulfate rapidly damaged the isolated glomeruli, resulting in foot process effacement and albumin leakage. Inhibition of calcium channels and chelation of extracellular calcium reduced protamine sulfate-induced damage, suggesting that calcium signaling plays a critical role in the initial stages of glomerular injury. Calcineurin inhibitors (FK506 and cyclosporine A) and the cathepsin L inhibitor E64 all inhibited protamine sulfate-mediated barrier changes, which suggests that calcium signaling acts, in part, through calcineurin- and cathepsin L-dependent cleavage of synaptopodin, a regulator of actin dynamics. The mTOR inhibitor rapamycin also protected glomeruli, demonstrating that calcium signaling has additional calcineurin-independent components. Furthermore, activation of Akt through mTOR had a direct role on glomerular barrier integrity, and activation of calcium channels mediated this process, likely independent of phosphoinositide 3-kinase. Taken together, these results demonstrate the importance of calcium and related signaling pathways in the structure and function of the glomerular filtration barrier.

Oleuropein: a novel immunomodulator conferring prolonged survival in experimental sepsis by Pseudomonas aeruginosa.

Oleuropein, a novel immunomodulator derived from olive tree, was assessed in vitro and in experimental sepsis by Pseudomonas aeruginosa. After addition in monocyte and neutrophil cultures, malondialdehyde, TNF-alpha, IL-6, and bacterial counts were estimated in supernatants. Acute pyelonephritis was induced in 70 rabbits after inoculation of pathogen in the renal pelvis. Intravenous therapy was administered in four groups postchallenge by one multidrug-resistant isolate (A, controls; B, oleuropein; C, amikacin; D, both agents) and in three groups postchallenge by one susceptible isolate (E, controls; F, oleuropein; G, amikacin). Survival was recorded; bacterial growth in blood and organs was counted; endotoxins (LPS), malondialdehyde, total antioxidant status, and TNF-alpha in serum were estimated. TNF-alpha and IL-6 of cell supernatants were not increased compared with controls when triggered by LPS and P. aeruginosa. Counts of multidrug-resistant P. aeruginosa were decreased in monocyte supernatants. Median survival of groups A, B, C, D, E, F, and G were 3.00, 6.00, 2.00, 10.00, 1.00, 5.00, and 1.00 days, respectively. Bacteria in blood were lower at 48 h in groups B and D compared with A and in groups F and G compared with E. Total antioxidant status decreased steadily over time in groups A, C, D, and G, but not in groups B and F. TNF-alpha of groups B, C, and D was lower than A at 48 h. Tissue bacteria decreased in group F compared with E. Oleuropein prolonged survival in experimental sepsis probably by promoting phagocytosis or inhibiting biosynthesis of proinflammatory cytokines.

FGF-23 and sFRP-4 in chronic kidney disease and post-renal transplantation.

BACKGROUND: The phosphatonins fibroblast growth factor-23 (FGF-23) and FRP-4 are inhibitors of tubular phosphate reabsorption that may play a role in the hyperphosphatemia associated with chronic kidney disease (CKD) or in the hypophosphatemia associated with renal transplants. METHODS: Plasma FGF-23, FRP-4, phosphorus and parathyroid hormone were measured in patients at all stages of CKD. Phosphate regulation of FGF-23 and secreted frizzled related protein-4 (sFRP-4) was examined in end-stage renal disease patients in the presence and absence of therapeutic phosphate binder usage. In renal transplant patients, plasma FGF-23, sFRP-4 and phosphorus concentrations were determined before and 4-5 days after transplantation. RESULTS: Plasma FGF-23 correlated with creatinine clearance (r2 = -0.584, p < 0.0001) and plasma phosphorus (r2 = 0.347, p < 0.001) in CKD patients and with plasma phosphorus (r2 = 0.448, p < 0.001) in end-stage renal disease patients. Phosphate binder withdrawal increased FGF-23 levels. In kidney transplant patients, dramatic decreases in FGF-23 (-88.8 +/- 5.4%) and phosphorus (-64 +/- 10.2%) were observed by 4-5 days post-transplantation. In patients with post-transplant hypophosphatemia, FGF-23 levels correlated inversely with plasma phosphorus (r2 = 0.661, p < 0.05). sFRP-4 levels did not change with creatinine clearance or hyperphosphatemia in CKD or end-stage renal disease patients, and no relation was noted between post-transplant sFRP-4 levels and hypophosphatemia. CONCLUSIONS: In CKD, FGF-23 levels rose with decreasing creatinine clearance rates and increasing plasma phosphorus levels, and rapidly decreased post-transplantation suggesting FGF-23 is cleared by the kidney. Residual FGF-23 may contribute to the hypophosphatemia in post-transplant patients.

Secreted frizzled-related protein 4 is a potent tumor-derived phosphaturic agent.

Tumors associated with osteomalacia elaborate the novel factor(s), phosphatonin(s), which causes phosphaturia and hypophosphatemia by cAMP-independent pathways. We show that secreted frizzled-related protein-4 (sFRP-4), a protein highly expressed in such tumors, is a circulating phosphaturic factor that antagonizes renal Wnt-signaling. In cultured opossum renal epithelial cells, sFRP-4 specifically inhibited sodium-dependent phosphate transport. Infusions of sFRP-4 in normal rats over 2 hours specifically increased renal fractional excretion of inorganic phosphate (FEPi) from 14% +/- 2% to 34% +/- 5% (mean +/- SEM, P < 0.01). Urinary cAMP and calcium excretion were unchanged. In thyro-parathyroidectomized rats, sFRP-4 increased FEPi from 0.7% +/- 0.2% to 3.8% +/- 1.2% (P < 0.05), demonstrating that sFRP-4 inhibits renal inorganic phosphate reabsorption by PTH-independent mechanisms. Administration of sFRP-4 to intact rats over 8 hours increased FEPi, decreased serum phosphate (1.95 +/- 0.1 to 1.53 +/- 0.09 mmol/l, P < 0.05) but did not alter serum 1alpha, 25-dihydroxyvitamin D, renal 25-hydroxyvitamin D 1alpha-hydroxylase cytochrome P450, and sodium-phosphate cotransporter mRNA concentrations. Infusion of sFRP-4 antagonizes Wnt action as demonstrated by reduced renal beta-catenin and increased phosphorylated beta-catenin concentrations. The sFRP-4 is detectable in normal human serum and in the serum of a patient with tumor-induced osteomalacia. Thus, sFRP-4 displays phosphatonin-like properties, because it is a circulating protein that promotes phosphaturia and hypophosphatemia and blunts compensatory increases in 1alpha, 25-dihydroxyvitamin D.

Focused assessment with sonography for trauma patients by clinicians: Initial experience and results.

OBJECTIVES: To describe the establishment of a service to provide bedside focused assessment sonography in trauma and to evaluate the service to date. SETTING: Emergency department of an urban trauma centre. METHODS: A prospective study of trauma patients who received a focused assessment sonography in trauma examination performed by a clinician managing the trauma in the emergency department. Accuracy was determined by comparing the scan interpretation with abdomino-pelvic computerized tomography, laparotomy or postmortem examination. RESULTS: The study period ran from 1 January 2000 to 11 September 2001 inclusive (20 months). One hundred and forty patients were included, with a final diagnosis established by computerized tomography (n = 124) and/or laparotomy (n = 18). There were 26 true-positives, 101 true-negatives, two false-positives and 11 false-negatives. Ten of the false-negative studies were performed by clinicians who had not reached accreditation. The sensitivity of focused assessment sonography in trauma was 70%, specificity 98% and diagnostic accuracy 91%. CONCLUSIONS: We have described the implementation of a clinician-based focused assessment sonography in trauma service within the emergency department with the support of radiology/ultrasound and trauma service. Processes for credentialling, quality assurance and training need to be in place. Significant issues exist with the length of time it takes clinicians to reach accreditation, in order that a critical mass of clinicians exists to provide a consistent service. The credentialling process should mandate a minimum number of supervised examinations.

Factors influencing prehospital and emergency department analgesia administration to patients with femoral neck fractures.

OBJECTIVES: To assess the analgesia practices of ambulance personnel and emergency department staff treating patients with fractured neck of femur. METHODS: This is a retrospective analysis of 176 patients with an admission diagnosis of fractured neck of femur, who presented to a major western Sydney teaching hospital, between January and November 1999. RESULTS: One hundred and twenty-eight patients met the inclusion criteria. The median age was 82, there were more female than male subjects. Ambulance officers made a clinical diagnosis of fractured neck of femur in 68% of cases. In 49% of cases no analgesia was given. Patients were given a higher triage category and pain relief faster if they had been given analgesia by ambulance officers, P = 0.0018 and P = 0.002, respectively. The median time to analgesia was 2 h 48 min. CONCLUSIONS: Only a modest proportion of patients with fractured neck of femur received prehospital analgesia and delays to analgesia in the emergency department are considerable. Strategies to address the delivery of appropriate analgesia to this group of patients should be developed.

Tumors associated with oncogenic osteomalacia express genes important in bone and mineral metabolism.

Oncogenic osteomalacia (OOM) is associated with primitive mesenchymal tumors that secrete phosphaturic factors resulting in low serum concentrations of phosphate and calcitriol, phosphaturia, and defective bone mineralization. To identify overexpressed genes in these tumors, we compared gene expression profiles of tumors resected from patients with OOM and histologically similar control tumors using serial analysis of gene expression (SAGE). Three hundred and sixty-four genes were expressed at least twofold greater in OOM tumors compared with control tumors. A subset of 67 highly expressed genes underwent validation with an extended set of OOM and control tumors using array analysis or reverse-transcription polymerase chain reaction (RT-PCR). Ten of these validated genes were consistently overexpressed in all OOM tumors relative to control tumors. Strikingly, genes with roles in bone matrix formation, mineral ion transport, and bone mineralization were highly expressed in the OOM tumors.