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Abstract PTPN2 (protein tyrosine phosphatase non-receptor type 2, or TC-PTP) and PTPN1 are attractive immuno-oncology targets, with the deletion of Ptpn1 and Ptpn2 improving response to immunotherapy in disease models. Targeted protein degradation has emerged as a promising approach to drug challenging targets including phosphatases. We developed potent PTPN2/N1 dual heterobifunctional degraders (Cmpd-1 and Cmpd-2) which facilitate efficient complex assembly with E3 ubiquitin ligase CRL4CRBN, and mediate potent PTPN2/N1 degradation in cells and mice. To provide mechanistic insights into the cooperative complex formation introduced by degraders, we employed a combination of structural approaches. Our crystal structure reveals how PTPN2 is recognized by the tri-substituted thiophene moiety of the degrader. We further determined a high-resolution structure of DDB1-CRBN/Cmpd-1/PTPN2 using single-particle cryo-electron microscopy (cryo-EM). This structure reveals that the degrader induces proximity between CRBN and PTPN2, albeit the large conformational heterogeneity of this ternary complex. The molecular dynamic (MD)-simulations constructed based on the cryo-EM structure exhibited a large rigid body movement of PTPN2 and illustrated the dynamic interactions between PTPN2 and CRBN. Together, our study demonstrates the development of PTPN2/N1 heterobifunctional degraders with potential applications in cancer immunotherapy. Furthermore, the developed structural workflow could help to understand the dynamic nature of degrader-induced cooperative ternary complexes.

Abstract The market approval of Tazemetostat (TAZVERIK) for the treatment of follicular lymphoma and epithelioid sarcoma has established “enhancer of zeste homolog 2” (EZH2) as therapeutic target in oncology. Despite their structural similarities and common mode of inhibition, Tazemetostat and other EZH2 inhibitors display differentiated pharmacological profiles based on their target residence time. Here we established high throughput screening methods based on time-resolved fluorescence energy transfer, scintillation proximity and high content analysis microscopy to quantify the biochemical and cellular binding of a chemically diverse collection of EZH2 inhibitors. These assays allowed to further characterize the interplay between EZH2 allosteric modulation by methylated histone tails (H3K27me3) and inhibitor binding, and to evaluate the impact of EZH2’s clinically relevant mutant Y641N on drug target residence times. While all compounds in this study exhibited slower off-rates, those with clinical candidate status display significantly slower target residence times in wild type EZH2 and disease-related mutants. These inhibitors interact in a more entropy-driven fashion and show the most persistent effects in cellular washout and antiproliferative efficacy experiments. Our work provides mechanistic insights for the largest cohort of EZH2 inhibitors reported to date, demonstrating that—among several other binding parameters—target residence time is the best predictor of cellular efficacy.

A simplified axisymmetric model of a transfemoral osseointegration implant was used to investigate the influence of the contact condition at the bone–implant interface on the vibrational response. The experimental setup allowed the degree of implant tightness to be controlled using a circumferential compression device affixed to the bone. Diametrically placed sensors allowed torsional modes to be distinguished from flexural modes. The results showed that the structural resonant frequencies did not shift significantly with tightness levels. The first torsional mode of vibration was found to be particularly sensitive to interface loosening. Harmonics in the vibrational response became prominent when the amplitude of the applied torque increased beyond a critical level. The torque level at which the third harmonic begins to rise correlated with implant criticality, suggesting a potential strategy for early detection of implant loosening based on monitoring the amplitude of the third harmonic of the torsional mode.

Injury remains a significant global health concern, with early major haemorrhage (MH) being a leading cause of preventable death. However, the absence of a standardised definition for MH hinders research comparability and optimal clinical decision-making.This scoping review aims to explore and categorise the published definitions of MH in adults following injury.A systematic search of the Medline (OVID) database and additional sources was conducted following established guidelines. Peer-reviewed articles published in English up to March 2023 were included if they related to injury, and critically unwell adult patients, and included reference to bleeding or haemorrhage.Out of 191 identified articles, 50 were included in the final analysis. These studies spanned from 2006 to 2023 and were conducted in various geographic locations. No consistent definition of MH was identified. Definitions of MH fell into six distinct categories: receipt of blood products, physiological parameters, scoring systems, clinical gestalt, observed bleeding (CT or clinical), and composite definitions. The ‘receipt of blood products’ category was the most frequent definition category, with massive transfusion (MT) ‘received’ being the most common definition of MH. Composite definitions and definitions involving the use of physiological parameters were also commonly employed.Our scoping review identified wide heterogeneity in the definition of MH following injury. The absence of a standardised definition for MH poses a significant challenge to both injury research and clinical practice. Addressing this gap is crucial in improving systems of trauma care and outcomes for critically bleeding patients.

Abstract Background Splenic artery embolisation (SAE) has become a vital strategy in the modern landscape of multidisciplinary trauma care, improving splenic salvage rates in patients with high-grade injury. However, due to a lack of prospective data there remains contention amongst stakeholders as to whether SAE should be performed at the time of presentation (prophylactic or pSAE), or whether patients should be observed, and SAE only used only if a patient re-bleeds. This systematic review aimed to assess published practice management guidelines which recommend pSAE, stratified according to their quality. Methods The study was registered and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Medline, PubMed, Cochrane, Embase, and Google Scholar were searched by the study authors. Identified guidelines were graded according to the Appraisal of Guidelines Research and Evaluation II (AGREE-II) instrument. Results Database and internet searches identified 1006 results. After applying exclusion criteria, 28 guidelines were included. The use of pSAE was recommended in 15 guidelines (54%). This included 6 out of 9 guidelines that were high quality (66.7%), 4 out of 9 guidelines that were moderate quality (44.4%), and 3 out of 10 (30%) guidelines that were low quality, p = 0.275. Conclusions This systematic review showed that recommendation of pSAE is more common in guidelines which are of high quality. However, there is vast heterogeneity of recommended practice guidelines, likely based on individual trauma systems rather than the available evidence. This reflects biases with interpretation of data and lack of multidisciplinary system inputs, including from interventional radiologists.

Abstract Background To which extent trauma- induced disturbances in ionized calcium (iCa2+) levels have a linear relationship with adverse outcomes remains controversial. The goal of this study was to determine the association between the distribution and accompanying characteristics of transfusion-independent iCa2+ levels versus outcome in a large cohort of major trauma patients upon arrival at the emergency department. Methods A retrospective observational analysis of the TraumaRegister DGU® (2015–2019) was performed. Adult major trauma patients with direct admission to a European trauma centre were selected as the study cohort. Mortality at 6 h and 24 h, in-hospital mortality, coagulopathy, and need for transfusion were considered as relevant outcome parameters. The distribution of iCa2+ levels upon arrival at the emergency department was calculated in relation to these outcome parameters. Multivariable logistic regression analysis was performed to determine independent associations. Results In the TraumaRegister DGU® 30 183 adult major trauma patients were found eligible for inclusion. iCa2+ disturbances affected 16.4% of patients, with hypocalcemia (

Introduction Transfusion of blood components is vital for the resuscitation of injured patients in hemorrhagic shock. Delays in initiating transfusion have been associated with harm, as has excess transfusion. The aim of this study was to evaluate variables associated with hospital mortality, with a focus on the two modifiable risk factors— time to initiate transfusion and volume of blood components—with hospital mortality.Methods This was a registry-based cohort study, including all consecutive adult patients presenting with hemorrhagic shock (systolic blood pressure (SBP) ≤90 mm Hg and transfusion of blood components) to a level 1 adult trauma center during a 5-year period (January 1, 2017–December 31, 2021). Associations with hospital mortality were assessed using multivariable logistic regression analysis, with final models developed using backward elimination.Results There were 195 patients included and there were 49 (25.1%) in-hospital deaths. The median time to first transfusion was 10 (IQR 6–16) minutes. Age (adjusted OR (aOR) 1.06; 95% CI: 1.03 to 1.08), initial SBP (aOR 0.96; 95% CI: 0.3 to 0.98), intracranial bleeding or diffuse axonal injury (aOR 2.63; 95% CI: 1.11 to 6.23), and the volume of blood components in the first 4 hours (aOR 1.08; 95% CI: 1.03 to 1.13) were associated with mortality. Time to transfusion was not associated with in-hospital mortality (aOR 0.99; 95% CI: 0.95 to 1.03). Among the 90 patients who underwent urgent transfer to the operating room or angiography suite, the median time to transfer was 2.38 hours (IQR 1.5–3.7). In this subgroup, age (aOR 1.11; 95% CI: 1.05 to 1.18) and volume of blood components (aOR 1.20; 95% CI: 1.08 to 1.34) were associated with mortality.Discussion In this setting where times to transfusion are short, further reductions in the time to transfusion are unlikely to improve outcome. In our population, for every unit of blood component transfused, the adjusted odds of death increased by 8%. These findings suggest investigation into strategies to achieve earlier control of hemorrhage.Level of evidence III.

Abstract Background Coronavirus disease 2019 (COVID-19) has exposed the disproportionate effects of pandemics on frontline workers and the ethical imperative to provide effective prophylaxis. We present a model for a pragmatic randomised controlled trial (RCT) that utilises Bayesian methods to rapidly determine the efficacy or futility of a prophylactic agent. Methods We initially planned to undertake a multicentre, phase III, parallel-group, open-label RCT, to determine if hydroxychloroquine (HCQ) taken once a week was effective in preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in healthcare workers (HCW) aged ≥ 18 years in New Zealand (NZ) and Ireland. Participants were to be randomised 2:1 to either HCQ (800 mg stat then 400 mg weekly) or no prophylaxis. The primary endpoint was time to Nucleic Acid Amplification Test-proven SARS-CoV-2 infection. Secondary outcome variables included mortality, hospitalisation, intensive care unit admissions and length of mechanical ventilation. The trial had no fixed sample size or duration of intervention. Bayesian adaptive analyses were planned to occur fortnightly, commencing with a weakly informative prior for the no prophylaxis group hazard rate and a moderately informative prior on the intervention log hazard ratio centred on ‘no effect’. Stopping for expected success would be executed if the intervention had a greater than 0.975 posterior probability of reducing the risk of SARS-CoV-2 infection by more than 10%. Final success would be declared if, after completion of 8 weeks of follow-up (reflecting the long half-life of HCQ), the prophylaxis had at least a 0.95 posterior probability of reducing the risk of SARS-CoV-2 infection by more than 10%. Futility would be declared if HCQ was shown to have less than a 0.10 posterior probability of reducing acquisition of SARS-CoV-2 infection by more than 20%. Discussion This study did not begin recruitment due to the marked reduction in COVID-19 cases in NZ and concerns regarding the efficacy and risks of HCQ treatment in COVID-19. Nonetheless, the model presented can be easily adapted for other potential prophylactic agents and pathogens, and pre-established collaborative models like this should be shared and incorporated into future pandemic preparedness planning. Trial registration The decision not to proceed with the study was made before trial registration occurred.

Abstract Objective In the ‘can’t intubate can’t oxygenate’ scenario, techniques to achieve front of neck access to the airway have been described in the literature but there is a lack of guidance on the optimal method for securing the tracheal tube (TT) placed during this procedure. The aim of this study was to compare three different methods of securing a TT to prevent extubation following a surgical cricothyroidotomy. Methods A randomised controlled trial was undertaken. The population studied were emergency physicians (EPs) attending a cadaveric airway course. The intervention was securing a TT placed via a surgical cricothyroidotomy by suture. The comparison was securing the TT using fabric tape with two different tying techniques. The primary outcome was the force required to extubate the trachea. The trial was registered with ANZCTR.org.au (ACTRN12621000320853). Results 17 emergency physicians completed intubations using all three of the securing methods on 12 cadavers for a total of 51 experiments. The mean extubation force was 6.54 KG (95 % CI 5.54–7.55) in the suture group compared with 2.28 KG (95 % CI 1.91–2.64) in the ‘Wilko tie’ group and 2.12 KG (95 % CI 1.63–2.60) in the ‘Lark’s foot tie’ group; The mean difference between the suture and fabric tie techniques was significant (p

Obturator hernias (OH) are rare, accounting for less than 0.05% of all hernias. The aetiology is usually attributed to chronically raised intra-abdominal pressure or cachexia with poor muscle mass. This case report describes a traumatic obturator hernia, an exceptionally rare aetiology of an already rare surgical condition. There are no previous reports of a traumatic obturator hernia in the current literature.This case reports upon the presentation, operative findings and management of a 48 year old male with abdominal and pelvic trauma following a motor bike collision. Laparotomy findings included a right sided traumatic incarcerated obturator foramen hernia with the comminuted pubic rami fracture trapping and piercing ileum within the hernia. In retrospect, the hernia was visible on CT scan. The hernia was repaired using biological mesh which was covered with adjacent peritoneum.As with much of trauma surgery, the management of this case required reliance on general principles and real time problem solving to address an issue not previously experienced by the operator, and not previously reported on in the current literature.

Abducens nerve palsy via direct or indirect injury is well described following head trauma likely due to its long anatomical course with several vulnerable segments. However, bilateral abducens palsies due to non-iatrogenic intracranial hypotension is unique. This report describes the case of a male with sequential delayed onset abducens nerve palsies following head and neck trauma due to intracranial hypotension secondary to cerebrospinal fluid (CSF) leak from a dural tear at the C6/7 level. Signs of intracranial hypotension were evident on magnetic resonance imaging (MRI). We hypothesise that the traction effect from ongoing CSF leak resulted in sequential palsies. His clinical course was also complicated by pulmonary embolus and a prolonged period of immobility, the anti-gravity effects of which likely mitigated the CSF leak in the early period. Conservative management was undertaken with bed rest, fluids and caffeine with good response and resolving abducens dysfunction after ten weeks. Further management with epidural blood patch or surgical fixation was not necessary and deemed unlikely to succeed given the location of the dural tear and the need for concurrent anticoagulation. It is important to recognise CSF leak and intracranial hypotension as potential, albeit rare, causes for sequential abducens nerve palsy in patients with head and spinal injuries. Management strategies of this condition range from conservative measures to surgical intervention.

Abstract Background The implementation of evidence-based protocols for stroke management in the emergency department (ED) for the appropriate triage, administration of tissue plasminogen activator to eligible patients, management of fever, hyperglycaemia and swallowing, and prompt transfer to a stroke unit were evaluated in an Australian cluster-randomised trial (T3 trial) conducted at 26 emergency departments. There was no reduction in 90-day death or dependency nor improved processes of ED care. We conducted an a priori planned process influential factors that impacted upon protocol uptake. Methods Qualitative face-to-face interviews were conducted with purposively selected ED and stroke clinicians from two high- and two low-performing intervention sites about their views on factors that influenced protocol uptake. All Trial State Co-ordinators (n = 3) who supported the implementation at the 13 intervention sites were also interviewed. Data were analysed thematically using normalisation process theory as a sensitising framework to understand key findings, and compared and contrasted between interviewee groups. Results Twenty-five ED and stroke clinicians, and three Trial State Co-ordinators were interviewed. Three major themes represented key influences on evidence uptake: (i) Readiness to change: reflected strategies to mobilise and engage clinical teams to foster cognitive participation and collective action; (ii) Fidelity to the protocols: reflected that beliefs about the evidence underpinning the protocols impeded the development of a shared understanding about the applicability of the protocols in the ED context (coherence); and (iii) Boundaries of care: reflected that appraisal (reflexive monitoring) by ED and stroke teams about their respective boundaries of clinical practice impeded uptake of the protocols. Conclusions Despite initial high ‘buy-in’ from clinicians, a theoretically informed and comprehensive implementation strategy was unable to overcome system and clinician level barriers. Initiatives to drive change and integrate protocols rested largely with senior nurses who had to overcome contextual factors that fell outside their control, including low medical engagement, beliefs about the supporting evidence and perceptions of professional boundaries. To maximise uptake of evidence and adherence to intervention fidelity in complex clinical settings such as ED cost-effective strategies are needed to overcome these barriers. Trial registration Australian New Zealand Clinical Trials Registry ( ACTRN12614000939695 ).

Abstract Background Multiple screening Duplex ultrasound scans (DUS) are performed in trauma patients at high risk of deep vein thrombosis (DVT) in the intensive care unit (ICU). Intensive care physician performed compression ultrasound (IP-CUS) has shown promise as a diagnostic test for DVT in a non-trauma setting. Whether IP-CUS can be used as a screening test in trauma patients is unknown. Our study aimed to assess the agreement between IP-CUS and vascular sonographer performed DUS for proximal lower extremity deep vein thrombosis (PLEDVT) screening in high-risk trauma patients in ICU. Methods A prospective observational study was conducted at the ICU of Alfred Hospital, a major trauma center in Melbourne, Australia, between Feb and Nov 2015. All adult major trauma patients admitted with high risk for DVT were eligible for inclusion. IP-CUS was performed immediately before or after DUS for PLEDVT screening. The paired studies were repeated twice weekly until the DVT diagnosis, death or ICU discharge. Written informed consent from the patient, or person responsible, or procedural authorisation, was obtained. The individuals performing the scans were blinded to the others’ results. The agreement analysis was performed using Cohen’s Kappa statistics and intraclass correlation coefficient for repeated binary measurements. Results During the study period, 117 patients had 193 pairs of scans, and 45 (39%) patients had more than one pair of scans. The median age (IQR) was 47 (28–68) years with 77% males, mean (SD) injury severity score 27.5 (9.53), and a median (IQR) ICU length of stay 7 (3.2–11.6) days. There were 16 cases (13.6%) of PLEDVT with an incidence rate of 2.6 (1.6–4.2) cases per 100 patient-days in ICU. The overall agreement was 96.7% (95% CI 94.15–99.33). The Cohen’s Kappa between the IP-CUS and DUS was 0.77 (95% CI 0.59–0.95), and the intraclass correlation coefficient for repeated binary measures was 0.75 (95% CI 0.67–0.81). Conclusions There is a substantial agreement between IP-CUS and DUS for PLEDVT screening in trauma patients in ICU with high risk for DVT. Large multicentre studies are needed to confirm this finding.

The aim of this systematic review was to evaluate the surgical, radiological, and functional outcomes of posterior-only versus combined anterior-posterior approaches in patients with traumatic thoracolumbar burst fractures. The ideal approach (anterior-only, posterior-only, or combined anterior-posterior) for the surgical management of thoracolumbar burst fracture remains controversial, with each approach having its advantages and disadvantages. A systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was performed (registration no., CRD42018115120). The authors reviewed comparative studies evaluating posterior-only approach compared with combined anterior-posterior approaches with respect to clinical, surgical, radiographic, and functional outcome measures. Five retrospective cohort studies were included. Postoperative neurological deterioration was not reported in either group. Operative time, estimated blood loss, and postoperative length of stay were increased among patients in the combined anterior-posterior group in one study and equivalent between groups in another study. No significant difference was observed between the two approaches with regards to long-term postoperative Cobb angle (mean difference, −0.2; 95% confidence interval, −5.2 to 4.8; p =0.936). Moreover, no significant difference in functional patient outcomes was observed in the 36item Short-Form Health Survey, Visual Analog Scale, and return-to-work rates between the two groups. The available evidence does not indicate improved clinical, radiologic (including kyphotic deformity), and functional outcomes in the combined anterior-posterior and posterior-only approaches in the management of traumatic thoracolumbar burst fractures. Further studies are required to ascertain if a subset of patients will benefit from a combined anterior-posterior approach.

Osseointegration implant has attracted significant attention as an alternative treatment for transfemoral amputees. It has been shown to improve patients’ sitting and walking comfort and control of the artificial limb, compared to the conventional socket device. However, the patients treated with osseointegration implants require a long rehabilitation period to establish sufficient femur–implant connection, allowing the full body weight on the prosthesis stem. Hence, a robust assessment method on the osseointegration process is essential to shorten the rehabilitation period and identify the degree of osseointegration prior to the connection of an artificial limb. This paper investigates the capability of a vibration-related index (E-index) on detecting the degree of simulated osseointegration process with three lengths of the residual femur (152, 190 and 228 mm). The adhesive epoxy with a setting time of 5 min was applied at the femur–implant interface to represent the stiffness change during the osseointegration process. The cross-spectrum and colormap of the normalised magnitude demonstrated significant changes during the cure time, showing that application of these plots could improve the accuracy of the currently available diagnostic techniques. Furthermore, the E-index exhibited a clear trend with a noticeable average increase of 53% against the cure time for all three residual length conditions. These findings highlight that the E-index can be employed as a quantitative justification to assess the degree of osseointegration process without selecting and tracing the resonant frequency based on the geometry of the residual femur.

Introduction The burden of injury in the Kingdom of Saudi Arabia (KSA) has increased in recent years, but the country has lacked a consistent methodology for collecting injury data. A trauma registry has been established at a large public hospital in Riyadh from which these data are now available.Objectives We aimed to provide an overview of trauma epidemiology by reviewing the first calendar year of data collection for the registry. Risk-adjusted analyses were performed to benchmark outcomes with a large Australian major trauma service in Melbourne. The findings are the first to report the trauma profile from a centre in the KSA and compare outcomes with an international level I trauma centre.Methods This was an observational study using records with injury dates in 2018 from the registries at both hospitals. Demographics, processes and outcomes were extracted, as were baseline characteristics. Risk-adjusted endpoints were inpatient mortality and length of stay. Binary logistic regression was used to measure the association between site and inpatient mortality.Results A total of 2436 and 4069 records were registered on the Riyadh and Melbourne databases, respectively. There were proportionally more men in the Saudi cohort than the Australian cohort (86% to 69%). The Saudi cohort was younger, the median age being 36 years compared with 50 years, with 51% of injuries caused by road traffic incidents. The risk-adjusted length of stay was 4.4 days less at the Melbourne hospital (95% CI 3.95 days to 4.86 days, p

We present the case of a 20-year-old male who was transferred to our Major Trauma Centre following a high-speed motor vehicle rollover. He arrived intubated with a right sided ICC in place. On arrival we elected to replace this ICC due to concerns regarding a superficial position, however 24 h after replacement, a large right sided pneumothorax developed. We suspect that both the pre-hospital ICC, as well as the ICC which we replaced it with, were unusually sited in the intrathoracic but extrapleural position.

Introduction Haemorrhage causes most preventable prehospital trauma deaths and about a third of in-hospital trauma deaths. Tranexamic acid (TXA), administered soon after hospital arrival in certain trauma systems, is an effective therapy in preventing or managing acute traumatic coagulopathy. However, delayed administration of TXA appears to be ineffective or harmful. The effectiveness of prehospital TXA, incidence of thrombotic complications, benefit versus risk in advanced trauma systems and the mechanism of benefit remain uncertain.Methods and analysis The Pre-hospital Anti-fibrinolytics for Traumatic Coagulopathy and Haemorrhage (The PATCH-Trauma study) is comparing TXA, initiated prehospital and continued in hospital over 8 hours, with placebo in patients with severe trauma at risk of acute traumatic coagulopathy. We present the trial protocol and an overview of the statistical analysis plan. There will be 1316 patients recruited by prehospital clinicians in Australia, New Zealand and Germany. The primary outcome will be the eight-level Glasgow Outcome Scale Extended (GOSE) at 6 months after injury, dichotomised to favourable (GOSE 5–8) and unfavourable (GOSE 1–4) outcomes, analysed using an intention-to-treat (ITT) approach. Secondary outcomes will include mortality at hospital discharge and at 6 months, blood product usage, quality of life and the incidence of predefined adverse events.Ethics and dissemination The study was approved by The Alfred Hospital Research and Ethics Committee in Victoria and also approved in New South Wales, Queensland, South Australia, Tasmania and the Northern Territory. In New Zealand, Northern A Health and Disability Ethics Committee provided approval. In Germany, Witten/Herdecke University has provided ethics approval. The PATCH-Trauma study aims to provide definitive evidence of the effectiveness of prehospital TXA, when used in conjunction with current advanced trauma care, in improving outcomes after severe injury.Trial registration number NCT02187120.

Background: Mass casualty incidents (MCIs) are increasing. Trauma centres play a key role in MCIs due to their readiness and expansive multidisciplinary expertise for injury management. Previous studies have shown deficiencies in trauma centre disaster preparedness. The aim of this study was to describe the current disaster preparedness of Major Trauma Centres (MTCs) in Australia, Canada, England and New Zealand. Methods: A cross-sectional survey of all (n = 82) MTCs was undertaken. The anonymous survey collected data about disaster preparedness in nine key areas. Respondents were encouraged to consult appropriately at their centre to provide an accurate representation of their centre's preparedness. Findings: Responses were received from 69 (84%) centres; 61 completed all questions. 91% had a disaster preparedness committee and 80% had an all-hazards emergency plan. 79% had held an MCI drill in the past 2 years. 54% reported a system in place to calculate maximum capacity, but testing of surge capacity was uncommon. 55% reported the presence of stored resources for an MCI and 58% had a database of staff trained in Emergency Management. 74% had a training and education plan available for staff involved in an MCI and a plan for professional debriefing of staff post-MCI, while 62% had a post-disaster employee assistance programme. Most centres had appropriate back-up communication, safety and security plans. Interpretation: The disaster preparedness of MTCs was high for communication, safety and security but there was clear need for improvement in other areas including surge capacity, human resources and post-disaster recovery. Keywords: Trauma centre, Disaster preparedness, Mass casualty incident, Survey, Major trauma

Osseointegrated prostheses are widely used following transfemoral amputation. However, this technique requires sufficient implant stability before and during the rehabilitation period to mitigate the risk of implant breakage and loosening. Hence, reliable assessment methods for the osseointegration process are essential to ensure initial and long–term implant stability. This paper researches the feasibility of a vibration analysis technique for the osseointegration (OI) process by investigating the change in the dynamic response of the residual femur with a novel implant design during a simulated OI process. The paper also proposes a concept of an energy index (the E–index), which is formulated based on the normalized magnitude. To illustrate the potential of the E–index, this paper reports on changes in the vibrational behaviors of a 133 mm long amputated artificial femur model and implant system, with epoxy adhesives applied at the interface to simulate the OI process. The results show a significant variation in the magnitude of the colormap against curing time. The study also shows that the E–index was sensitive to the interface stiffness change, especially during the early curing process. These findings highlight the feasibility of using the vibration analysis technique and the E–index to quantitatively monitor the osseointegration process for future improvement on the efficiency of human health monitoring and patient rehabilitation.

Reliable and quantitative assessments of bone quality and fracture healing prompt well-optimised patient healthcare management and earlier surgical intervention prior to complications of nonunion and malunion. This study presents a clinical investigation on modal frequencies associations with musculoskeletal components of human legs by using a prototype device based on a vibration analysis method. The findings indicated that the first out-of-plane and coupled modes in the frequency range from 60 to 110 Hz are associated with the femur length, suggesting these modes are suitable quantitative measures for bone evaluation. Furthermore, higher-order modes are shown to be associated with the muscle and fat mass of the leg. In addition, mathematical models are formulated via a stepwise regression approach to determine the modal frequencies using the measured leg components as variables. The optimal models of the first modes consist of only femur length as the independent variable and explain approximately 43% of the variation of the modal frequencies. The subsequent findings provide insights for further development on utilising vibration-based methods for practical bone and fracture healing monitoring.

Abstract Background Theoretical frameworks and models based on behaviour change theories are increasingly used in the development of implementation interventions. Development of an implementation intervention is often based on the available evidence base and practical issues, i.e. feasibility and acceptability. The aim of this study was to describe the development of an implementation intervention for the T3 Trial (Triage, Treatment and Transfer of patients with stroke in emergency departments (EDs)) using theory to recommend behaviour change techniques (BCTs) and drawing on the research evidence base and practical issues of feasibility and acceptability. Methods A stepped method for developing complex interventions based on theory, evidence and practical issues was adapted using the following steps: (1) Who needs to do what, differently? (2) Using a theoretical framework, which barriers and enablers need to be addressed? (3) Which intervention components (behaviour change techniques and mode(s) of delivery) could overcome the modifiable barriers and enhance the enablers? A researcher panel was convened to review the list of BCTs recommended for use and to identify the most feasible and acceptable techniques to adopt. Results Seventy-six barriers were reported by hospital staff who attended the workshops (step 1: thirteen TDF domains likely to influence the implementation of the T3 Trial clinical intervention were identified by the researchers; step 2: the researcher panellists then selected one third of the BCTs recommended for use as appropriate for the clinical context of the ED and, using the enabler workshop data, devised enabling strategies for each of the selected BCTs; and step 3: the final implementation intervention consisted of 27 BCTs). Conclusions The TDF was successfully applied in all steps of developing an implementation intervention for the T3 Trial clinical intervention. The use of researcher panel opinion was an essential part of the BCT selection process to incorporate both research evidence and expert judgment. It is recommended that this stepped approach (theory, evidence and practical issues of feasibility and acceptability) is used to develop highly reportable implementation interventions. The classifying of BCTs using recognised implementation intervention components will facilitate generalisability and sharing across different conditions and clinical settings.

Whilst post-traumatic respiratory failure is the most common indication for use of VV-ECMO in trauma patients, its use in traumatic thoracic compartment syndrome is not yet well described. Thoracic compartment syndrome, a rare complication of thoracic trauma, occurs in the setting of chest wall injuries, impaired chest wall compliance, pulmonary contusions and subsequent high ventilatory pressures. This in turn impairs venous return and increases risk of circulatory arrest due to obstructive shock.This case study describes the successful use of VV-ECMO in a young male with thoracic compartment syndrome following severe blunt chest trauma sustained in a high speed motor vehicle crash. Following brief circulatory arrest, thoracic compartment syndrome was relieved during thoracotomy but reoccurred on chest closure. The use of VV-ECMO for oxygenation permitted lower ventilatory pressures, allowing venous return and primary closure of the thoracotomy. The patient subsequently had an excellent functional outcome.This case describes the successful use of VV-ECMO for a novel indication. The indications for ECMO in thoracic trauma patients continue to evolve. Keywords: Shock, Traumatic, Thoracic injuries, Treatment, ECMO, Trauma, Compartment syndromes, Accidents, Traffic

Background: Clinical reasoning utilizing certain symptoms and scores has not proven to be a reliable decision-making tool to determine whether or not to suspect a group A Streptococcus (GAS) infection in the patient presenting with a sore throat. Culture as the so-called ‘gold standard’ is impracticable because it takes 1 to 2 days (and even longer in remote locations) for a result, and thus treatment decisions will be made without the result available. Rapid diagnostic antigen tests have demonstrated sufficient sensitivities and specificities in detecting GAS antigens to identify GAS throat infections. Methods: Throat swab samples were collected from patients attending the Mount Isa Hospital emergency department for a sore throat; these samples were compared to swab samples collected from healthy controls who did not have a sore throat. Both groups were aged 3–15 years. All swab samples were analyzed with a point-of-care test (Alere Test Pack +Plus with OBC Strep A). The etiologic predictive value (EPV) of the throat swab was calculated. Results: The 95% confidence interval for positive EPV was 88–100% and for negative EPV was 97–99%, depending on assumptions made. Conclusion: This study demonstrates that the point-of-care test Alere Test Pack +Plus Strep A has a high positive predictive value and is able to rule in GAS infection as long as the proportion of carriers is low. Also the negative predictive value for ruling out GAS as the etiologic agent is very high irrespective of the carrier rate. Hence, this test is always useful to rule out GAS infection.

This review presents seven national asthma programmes to support the European Asthma Research and Innovation Partnership in developing strategies to reduce asthma mortality and morbidity across Europe. From published data it appears that in order to influence asthma care, national/regional asthma programmes are more effective than conventional treatment guidelines. An asthma programme should start with the universal commitments of stakeholders at all levels and the programme has to be endorsed by political and governmental bodies. When the national problems have been identified, the goals of the programme have to be clearly defined with measures to evaluate progress. An action plan has to be developed, including defined re-allocation of patients and existing resources, if necessary, between primary care and specialised healthcare units or hospital centres. Patients should be involved in guided self-management education and structured follow-up in relation to disease severity. The three evaluated programmes show that, thanks to rigorous efforts, it is possible to improve patients' quality of life and reduce hospitalisation, asthma mortality, sick leave and disability pensions. The direct and indirect costs, both for the individual patient and for society, can be significantly reduced. The results can form the basis for development of further programme activities in Europe.

BackgroundImproved understanding of the quality of survival of patients is crucial in evaluating trauma care, understanding recovery patterns and timeframes, and informing healthcare, social, and disability service provision. We aimed to describe the longer-term health status of seriously injured patients, identify predictors of outcome, and establish recovery trajectories by population characteristics.Methods and findingsA population-based, prospective cohort study using the Victorian State Trauma Registry (VSTR) was undertaken. We followed up 2,757 adult patients, injured between July 2011 and June 2012, through deaths registry linkage and telephone interview at 6-, 12-, 24-, and 36-months postinjury. The 3-level EuroQol 5 dimensions questionnaire (EQ-5D-3L) was collected, and mixed-effects regression modelling was used to identify predictors of outcome, and recovery trajectories, for the EQ-5D-3L items and summary score. Mean (SD) age of participants was 50.8 (21.6) years, and 72% were male. Twelve percent (n = 333) died during their hospital stay, 8.1% (n = 222) of patients died postdischarge, and 155 (7.0%) were known to have survived to 36-months postinjury but were lost to follow-up at all time points. The prevalence of reporting problems at 36-months postinjury was 37% for mobility, 21% for self-care, 47% for usual activities, 50% for pain/discomfort, and 41% for anxiety/depression. Continued improvement to 36-months postinjury was only present for the usual activities item; the adjusted relative risk (ARR) of reporting problems decreased from 6 to 12 (ARR 0.87, 95% CI: 0.83-0.90), 12 to 24 (ARR 0.94, 95% CI: 0.90-0.98), and 24 to 36 months (ARR 0.95, 95% CI: 0.95-0.99). The risk of reporting problems with pain or discomfort increased from 24- to 36-months postinjury (ARR 1.06, 95% CI: 1.01, 1.12). While loss to follow-up was low, there was responder bias with patients injured in intentional events, younger, and less seriously injured patients less likely to participate; therefore, these patient subgroups were underrepresented in the study findings.ConclusionsThe prevalence of ongoing problems at 3-years postinjury is high, confirming that serious injury is frequently a chronic disorder. These findings have implications for trauma system design. Investment in interventions to reduce the longer-term impact of injuries is needed, and greater investment in primary prevention is needed.

Background and Objectives: Major trauma centres manage severely injured patients using multi-disciplinary teams but the evidence-base that targeted Trauma Team Training (TTT) improves patients’ outcomes is unclear. This systematic review aimed to identify the association between the implementation of TTT programs and patient outcomes. Materials and Methods: We searched OVID Medline, PubMed and The Cochrane Library (CENTRAL) from the date of the database commencement until 10 of April 2019 for a combination of Medical Subject Headings (MeSH) terms and keywords relating to TTT and clinical outcomes. Reference lists of appraised studies were also screened for relevant articles. We extracted data on the study setting, type and details about the learners, as well as clinical outcomes of mortality and/or time to critical interventions. A meta-analysis of the association between TTT and mortality was conducted using a random effects model. Results: The search yielded 1136 unique records and abstracts, of which 18 full texts were reviewed. Nine studies met final inclusion, of which seven were included in a meta-analysis of the primary outcome. There were no randomised controlled trials. TTT was not associated with mortality (Pooled overall odds ratio (OR) 0.83; 95% Confidence Interval; 0.64−1.09). TTT was associated with improvements in time to operating theatre and time to first computerized tomography (CT) scanning. Conclusions: Despite few publications related to TTT, its introduction was associated with improvements in time to critical interventions. Whether such improvements can translate to improvements in patient outcomes remains unknown. Further research focusing on the translation of standardised trauma team reception “actions” into TTT is required to assess the association between TTT and patient outcome.

The lack of a quantitative method to adequately assess fractured bone healing that has undergone fixation limits prognostic capabilities on patients’ optimal return to work. This paper addresses the use of vibrational analysis to monitor the state of healing of a plate-screw fixated femur and supplement the current clinical radiographic assessment. This experimental study involves an osteotomised composite femur specimen enclosed by modelling clay to simulate the damping effect of overlying soft tissues. Epoxy adhesives are applied to the fractured region and to simulate the healing process. With the instrumentation described, the cross-spectrum and coherence are obtained and analysed in the frequency domain over a period of time. The results suggest that it is crucial to analyse the cross-spectrum and proposed healing index to quantitatively assess the stages of healing. The results also show that the mass loading effect due to modelling clay did not influence the proposed healing assessment technique. The findings indicate a potential non-intrusive technique to evaluate the healing of fractured femur by utilising the vibrational responses.

Quantitative and reliable monitoring of osseointegration will help further evaluate the integrity of the orthopaedic construct to promote novel prosthesis design and allow early mobilisation. Quantitative assessment of the degree or the lack of osseointegration is important for the clinical management with the introduction of prosthetic implants to amputees. Acousto-ultrasonic wave propagation has been used in structural health monitoring as well as human health monitoring but so far has not extended to osseointegrated implants or prostheses. This paper presents an ultrasonic guided wave approach to assess the osseointegration of a novel implant. This study explores the potential of integrating structural health monitoring concepts into a new osseointegrated implant. The aim is to demonstrate the extension of acousto-ultrasonic techniques, which have been widely reported for the structural health monitoring of engineering structures, to assess the state of osseointegration of a bone and implant. To illustrate this potential, this paper will report on the experimental findings which investigated the unification of an aluminium implant and bone-like geometry surrogate. The core of the test specimen is filled with silicone and wrapped with plasticine to simulate the highly damped cancellous bone and soft tissue, respectively. To simulate the osseointegration process, a 2-h adhesive epoxy is used to bond the surrogate implant and a bone-like structure. A series of piezoelectric elements are bonded onto the surrogate implant to serve as actuators and sensors. The actuating piezoelectric element on an extramedullary strut is excited with a 1 MHz pulse signal. The reception of the ultrasonic wave by the sensing elements located on the adjacent and furthest struts is used to assess the integration of this implant to the parent bone structure. The study shows an Osseointegration Index can be formulated by using engineering and acousto-ultrasonic methods to measure the unification of a bone and implant. This also highlights a potential quantitative evaluation technique regardless of bone-implant geometry and soft tissue damping.

BACKGROUND: In 2010, the Canadian Thoracic Society (CTS) published a Consensus Summary for the diagnosis and management of asthma in children six years of age and older, and adults, including an updated Asthma Management Continuum. The CTS Asthma Clinical Assembly subsequently began a formal clinical practice guideline update process, focusing, in this first iteration, on topics of controversy and/or gaps in the previous guidelines.

BACKGROUND: Noneosinophilic asthma has been regarded as a distinct phenotype characterized by a poor response to inhaled corticosteroids (ICS).

Introduction. Management of haemodynamically stable patients with penetrating abdominal injuries varies from nonoperative to operative management. The aim was to investigate whether peritoneal breach when used as an indication for exploratory laparotomy appropriately identified patients with intra-abdominal visceral injury. Methods. We conducted retrospective cohort study of all patients presenting with PAI at a major trauma centre from January 2007 to December 2011. We measured the incidence of peritoneal breach and correlated this with intra-abdominal visceral injury diagnosed at surgery. Results. 252 patients were identified with PAI. Of the included patients, 71 were managed nonoperatively and 118 operatively. The operative diagnoses included nonperitoneal-breaching injuries, intraperitoneal penetration without organ damage, or intraperitoneal injury with organ damage. The presenting trauma CT scan was reported as normal in 63%, 34%, and 2% of these groups, respectively. The total negative laparotomy/laparoscopy rate for all patients presented with PAI was 21%, almost half of whom had a normal CT scan. Conclusion. We found that peritoneal breach on its own does not necessarily always equate to intra-abdominal visceral injury. Observation with sequential examination for PAI patients with a normal CT scan may be more important than exclusion of peritoneal breach via laparoscopy.

BACKGROUND: There are no published studies that have assessed whether adding long-acting beta 2-agonist bronchodilators and/or inhaled steroids to chronic therapy with tiotropium would provide additional clinical benefit to patients with moderate to severe chronic obstructive pulmonary disease (COPD).

OBJECTIVES: To estimate the magnitude of antituberculous drug resistance and identify prospectively the risk factors for its development in tuberculosis (TB) patients in western Canada over a one-year period.