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Background Cigarette smoking is associated with an increased risk of developing ARDS. However, whether changes in smoking patterns or processes of care impact this relationship is unclear. Research Question Are changes in smoking and resuscitation patterns associated with changes in the relationship between smoking and ARDS? Study Design and Methods We conducted a prospective cohort study of critically injured adults with blunt trauma from 2005 to 2015. Plasma cotinine, a tobacco biomarker, was measured to categorize patients by smoking status. We used regression to assess the relationship between smoking, resuscitation practices, and ARDS over time. Results In the overall cohort, active (OR, 1.9; 95% CI, 1.0-3.5; P = .046) and passive (OR, 2.6; 95% CI, 1.4-4.8; P = .002) smoking were associated with an increased risk of developing ARDS in multivariate analyses. In contrast to the dose-response relationship in patients enrolled from 2005 to 2008, passive cigarette smoke exposure was associated with the highest risk of developing ARDS in patients enrolled from 2009 to 2015, suggesting a threshold effect. Packed RBC (pRBC) and fresh frozen plasma (FFP) transfusions were associated with an increased risk of developing ARDS, particularly in active smokers (pRBC: OR, 5.6; P Interpretation Despite changes in resuscitation and smoking patterns, cigarette smoking remains associated with an increased risk of developing ARDS. However, this relationship changed over time, with passive smokers at particularly increased risk of developing ARDS in later years, which may be related to changes in smoking patterns or transfusion practices over time. These findings highlight the need for additional mechanistic and epidemiologic studies of the effects of low levels of cigarette smoke exposure on lung health.

BackgroundAcute respiratory distress syndrome (ARDS) following trauma is historically associated with crystalloid and blood product exposure. Advances in resuscitation have occurred over the last decade, but their impact on ARDS is unknown. We sought to investigate predictors of postinjury ARDS in the era of hemostatic resuscitation.MethodsData were prospectively collected from arrival to 28 days for 914 highest-level trauma activations who required intubation and survived more than 6 hours from 2005 to 2016 at a Level I trauma center. Patients with ratio of partial pressure of oxygen to fraction of inspired oxygen of 300 mmHg or less during the first 8 days were identified. Two blinded expert clinicians adjudicated all chest radiographs for bilateral infiltrates in the first 8 days. Those with left-sided heart failure detected were excluded. Multivariate logistic regression was used to define predictors of ARDS.ResultsOf the 914 intubated patients, 63% had a ratio of partial pressure of oxygen to fraction of inspired oxygen of 300 or less, and 22% developed ARDS; among the ARDS cases, 57% were diagnosed early (in the first 24 hours), and 43% later. Patients with ARDS diagnosed later were more severely injured (ISS 32 vs. 20, p = 0.001), with higher rates of blunt injury (84% vs. 72%, p = 0.008), chest injury (58% vs. 36%, p < 0.001), and traumatic brain injury (72% vs. 48%, p < 0.001) compared with the no ARDS group. In multivariate analysis, head/chest Abbreviated Injury Score scores, crystalloid from 0 to 6 hours, and platelet transfusion from 0 to 6 hours and 7 to 24 hours were independent predictors of ARDS developing after 24 hours.ConclusionsBlood and plasma transfusion were not independently associated with ARDS. However, platelet transfusion was a significant independent risk factor. The role of platelets warrants further investigation but may be mechanistically explained by lung injury models of pulmonary platelet sequestration with peripheral thrombocytopenia.Level of evidencePrognostic study, level IV.

OBJECTIVE: To determine if clinical evaluations of post-stroke arm function correspond to everyday motor performance indexed by arm accelerometers. DESIGN: Cross-sectional study analyzing baseline data from a larger trial (NCT02665052). SETTING: Outpatient research center. PARTICIPANTS: Twenty community-dwelling adults with chronic arm motor deficits (stroke≥6mo). INTERVENTION: 72-hours of home wrist-worn accelerometry during normal routine. MAIN OUTCOME MEASURES: Clinical evaluations included the Fugl-Meyer (FM), Action Research Arm Test (ARAT), Wolf Motor Function Test (WMFT), and two self-assessments: the Motor Activity Log (MAL) and hand motor subscale of the Stroke Impact Scale (SIS). Accelerometer-derived variables included quantifications of movement intensity (magnitude) and duration of arm use. RESULTS: Participants had moderate arm impairment (FM 36.1 ± 9.4). The accelerometer-derived mean magnitude ratio correlated significantly with the FM (ρ = 0.60, p < 0.01), WMFT functional score (ρ = 0.59, p < 0.01), and ARAT (ρ = 0.50, p < 0.05). The hours of use ratio correlated with the MAL amount of use (ρ = 0.58, p < 0.01) and quality of movement (ρ = 0.61, p < 0.01). Total paretic hours did not correlate with the FM, WMFT or ARAT, and intensity variables did not correlate with the MAL or SIS. CONCLUSIONS: Participants with higher baseline function had greater intensity of paretic arm movement at home; similarly, those who perceived they had less disability used their paretic arm more relative to their non-paretic arm. However, some participants with higher clinical scores did not exhibit greater arm use in everyday life, possibly due to neglect and learned non-use. Therefore, individualized home accelerometry profiles could provide valuable insight to better tailor post-stroke rehabilitation.

Background Physical rehabilitation services are an important component of treatment for persons with multiple sclerosis (PwMS) to improve and maintain physical mobility. However, PwMS often have significant barriers to outpatient physical therapy (PT) services including mobility deficits and lack of transportation. The integration of exercise gaming (exergaming) and telehealth into clinical PT practices may overcome these barriers. The overarching purpose of this pilot study was to evaluate the acceptability and effects of an individualized telePT intervention using exergaming. Methods Ten individuals with multiple sclerosis (MS) completed a 12-week exergaming (Jintronix®) telerehabilitation intervention. In order to measure the acceptability of the telerehabilitation intervention, adherence was measured through the tablet-based rehabilitation software and each participant completed a satisfaction questionnaire. Clinical outcome measures were assessed at baseline and post-intervention. To evaluate the efficacy of this intervention, the following measures of physical function and fatigue were included; the Short Physical Performance Battery (SPPB), 25-Foot Walk (25FW), Modified Fatigue Impact Scale (MFIS), Multiple Sclerosis Walking Scale-12 (MSWS), and the 2-Minute Walk Test (2MWT). Clinical outcomes were analyzed using the Sign test and Wilcoxon signed rank test. All other data were evaluated using descriptive statistics. Results After the intervention, participants demonstrated significant improvements in ambulation speed during the 25FW (p = 0.04) and ambulation distance during the 2MWT (p = 0.002). Statistically significant increases of SPPB total score (p = .04) and sub-scores were also found. Participants did not demonstrate significant changes in the MFIS (p = 0.31) or MSWS-12 (p = 0.06) after the intervention. Participants had a 58.3% adherence rate during the intervention and performed their exercise program an average of 2.5 times per week. All participants reported that they were either ‘satisfied or ‘very satisfied’ with their telerehabilitation experience, would use telerehabilitation again, and would recommend telerehabilitation to others. Conclusion This individualized telerehabilitation intervention which integrates exergaming and clinical video teleconferencing is acceptable to patients and may offer a viable alternative to traditional PT for PwMS. Trial registration NCT03655431, retrospectively registered on August 31st, 2018.

Patient portals (PPs) foster engagement and self-management of chronic disease and are emerging as extensions of the care continuum. Utilisation from a health service delivery perspective is growing; however, it is a relatively new model of care in the field of rehabilitation. This pilot, within a larger randomised controlled stroke rehabilitation trial, explored the feasibility and acceptance of secure messaging using an established nationwide PP system for e-visits. Fifteen participants with stroke-related arm disability were randomised to 6 weeks of home arm telerehabilitation. All were over the age of 60 and 73% lived with a spouse or significant other. Mean intervention time was 6.8 weeks, and participants sent 2.3 ± 1.4 messages per week to complete 15.1 h of reported therapy (prescribed therapy = 18 h). Portal use improved therapist efficiency and resulted in a 1:6 therapist to patient exercise time ratio compared with the conventional 1:1 ratio for in-person therapy. Low initial electronic health literacy, self-efficacy or cognitive scores did not prohibit utilisation, and satisfaction with secure messaging for patient–therapist communication was 3.5 ± 1.2 out of 5. Overall, PP-supported e-visits were a feasible and acceptable telerehabilitation care delivery method for this chronic stroke population. ClinicalTrials.gov Identifier NCT02665052. Registered 27 January 2016. https://clinicaltrials.gov/ct2/show/NCT02665052

Background: Stroke-related ankle dysfunction due to hemiparesis has a profound negative impact on gait biomechanics and walking. Task-oriented treadmill training improves gait velocity but does not lead to restitution of ankle function. Advances in robotic technology have led to the development of an adaptive ankle robot that can be integrated into treadmill walking and provide precisely timed graded assistance consistent with motor learning approaches. The aim of this study was to compare the effectiveness of a 6-week treadmill-integrated adaptive ankle robot (TMR) training to 6-weeks of treadmill training (TM) alone on improved paretic ankle motor control and gait performance. Methods: This was a single-blind (evaluator-blinded) randomized controlled trial. 45 participants received either TMR or TM training 3 times per week for 6 weeks. Primary outcomes were improved peak paretic ankle dorsiflexion (DF) angle at swing, improved DF angle at foot strike (weight acceptance), and increased gait velocity during self-selected over-ground walking. The primary analysis was based on intention-to-treat using a longitudinal regression model. An additional sub-set analysis of subjects with biomechanically defined foot drop was performed. Results: There were no significant post-training ankle dorsiflexion or gait velocity differences between groups. Six-week post-training mean peak paretic DF swing angle was (4.84 ± 6.83; 4.2 ± 6.83 p=0.63) and DF angle at foot strike was (-0.70 ± 6.55; -0.46 ± 5.70 p=0.84) respectively for TMR and TM. Gait velocity gains were similar and TMR had a mean increase of 0.54 m/s ± 0.24 and TM increased 0.56 m/s ±0.32. p=0.48 post-training.Conclusion: Integrating adaptive ankle robotics into task-specific locomotor training was not significantly better than treadmill training alone. Both interventions improved gait velocity. Promising results in ankle motor control were seen in a subset of subjects with biomechanically defined foot drop that warrants further investigation. Clinical Trial Registration: Clinical trials.gov id: NCT02483676. Registered June 29, 2015, https://clinicaltrials.gov/ct2/show/NCT02483676

Goal-directed hemostatic resuscitation based on thrombelastography (TEG) has a survival benefit compared with conventional coagulation assays such as international normalized ratio, activated partial thromboplastin time, fibrinogen level, and platelet count. While TEG-based transfusion thresholds for patients at risk for massive transfusion (MT) have been defined using rapid TEG, cutoffs have not been defined for TEG using other activators such as kaolin. The purpose of this study was to develop thresholds for blood product transfusion using citrated kaolin TEG (CK-TEG) in patients at risk for MT.CK-TEG was assessed in trauma activation patients at two Level 1 trauma centers admitted between 2010 and 2017. Receiver operating characteristic (ROC) curve analyses were performed to test the predictive performance of CK-TEG measurements in patients requiring MT, defined as10 units of red blood cells or death within the first 6 hours. The Youden Index defined optimal thresholds for CK-TEG-based resuscitation.Of the 825 trauma activations, 671 (81.3%) were men, 419 (50.8%) suffered a blunt injury, and 62 (7.5%) received a MT. Patients who had a MT were more severely injured, had signs of more pronounced shock, and more abnormal coagulation assays. CK-TEG R-time was longer (4.9 vs. 4.4 min, p = 0.0084), angle was lower (66.2 vs. 70.3 degrees, p0.0001), maximum amplitude was lower in MT (57 vs. 65.5 mm, p0.0001), and LY30 was greater (1.8% vs. 1.2%, p = 0.0012) in patients with MT compared with non-MT. To predict MT, R-time yielded an area under the ROC curve (AUROC) = 0.6002 and a cut point of4.45 min. Angle had an AUROC = 0.6931 and a cut point of67 degrees. CMA had an AUROC = 0.7425, and a cut point of60 mm. LY30 had an AUROC = 0.623 with a cut point of4.55%.We have identified CK-TEG thresholds that can guide MT in trauma. We propose plasma transfusion for R-time4.45 min, fibrinogen products for an angle67 degrees, platelet transfusion for MA60 mm, and antifibrinolytics for LY304.55%.Therapeutic study, level V.

Background Posttraumatic acute respiratory distress syndrome (ARDS) is associated with prolonged mechanical ventilation and longer hospitalizations. The relationship between posttraumatic ARDS severity and financial burden has not been previously studied. We hypothesized that increasing ARDS severity is associated with incrementally higher health care costs. Methods Adults arriving as the highest level of trauma activation were enrolled in an ongoing prospective cohort study. Patients who survived 6 hours or longer are included in the analysis. Blinded review of chest radiographs was performed by two independent physicians for any intubated patient with PaO2:FIO2 ratio of 300 mmHg or lower during the first 8 days of admission. The severity of ARDS was classified by the Berlin criteria. Hospital charge data were used to perform standard costing analysis. Results Acute respiratory distress syndrome occurred in 13% (203 of 1,586). The distribution of disease severity was 33% mild, 42% moderate, and 25% severe. Patients with ARDS were older (41 years vs. 35 years, p Conclusion The development of posttraumatic ARDS is associated with higher health care costs. Among trauma patients who develop ARDS, total hospital charges per day increase with worsening severity of disease. Prevention, early recognition, and treatment of ARDS after trauma are potentially important objectives for efforts to control health care costs in this population. Level of evidence Economic and value-based evaluations, level IV.

Background The risk of the acute respiratory distress syndrome (ARDS) is increased in passive and active smokers after blunt trauma. However, the mechanisms responsible, including the role of platelet aggregation, for this association are unknown. Methods We analyzed 215 patients with severe blunt trauma from a prospective observational cohort at a Level I trauma center between 2010 and 2015. Subjects underwent impedance-based platelet aggregometry in response to platelet agonists arachidonic acid, adenosine diphosphate, collagen, and thrombin receptor activating peptide-6. Acute respiratory distress syndrome within the first 8 days of admission was adjudicated using Berlin criteria. Plasma cotinine was measured to assess cigarette smoke exposure. Regression analyses were used to assess the relationship between (1) platelet aggregation and ARDS and (2) cigarette smoke exposure and platelet aggregation. Results At both 0 hour and 24 hours, impaired platelet aggregation was associated with increased odds of developing ARDS. Cigarette smoke exposure was associated with increased platelet aggregation upon arrival to the emergency department. However, at 24 hours, cigarette smoke exposure was associated with increased impairment in platelet aggregation, reflecting a statistically significant decline in platelet aggregation over the initial 24 hours after trauma. The relationship between this decline in platelet aggregation and ARDS differed by cigarette smoke exposure status, suggesting that impaired platelet activation differentially affects the risk of ARDS in those with cigarette smoke exposure (arachidonic acid, p for interaction: 0.005, collagen p for interaction: 0.02, adenosine diphosphate, p for interaction: 0.05). Conclusion Impaired platelet aggregation at 0 hour and 24 hours is associated with an increased risk of developing ARDS after severe blunt trauma. Cigarette smoke-exposed patients are more likely to develop impaired platelet aggregation over the first 24 hours of admission, which may contribute to their increased risk of ARDS. Level of evidence Prognostic/Epidemiological, level III.

Objective To quantitatively determine levels of upper extremity movement impairment by using a cluster analysis of the Fugl-Meyer Assessment of the Upper Extremity (FMA-UE) with and without reflex items. Design Secondary analysis. Setting University and research centers. Participants Individuals (N=247) with chronic stroke (>6mo poststroke). Interventions Not applicable. Main Outcome Measures Cutoff scores defined by FMA-UE total scores of clusters identified by 2 hierarchical cluster analyses performed on the full sample of FMA-UE individual item scores (with and without reflexes). Patterns of motor function defined by aggregate item scores of clusters. Results FMA-UE scores ranged from 2 to 63 (mean, 26.9±15.7) with reflex items and from 0 to 57 (mean, 22.1±15.3) without reflex items. Three clusters were identified. The distributions of the FMA-UE scores revealed considerable overlap between the clusters; therefore, 4 distinct stroke impairment levels were derived. Conclusions For chronic stroke, the cluster analysis of the FMA-UE supports either a 3- or a 4-impairment level classification scheme.

Objective: To demonstrate the feasibility of algorithmic prediction using a model of baseline arm movement, genetic factors, demographic characteristics, and multimodal assessment of the structure and function of motor pathways. To identify prognostic factors and the biological substrate for reductions in arm impairment in response to repetitive task practice. Design: This prospective single-group interventional study seeks to predict response to a repetitive task practice program using an intent-to-treat paradigm. Response is measured as a change of ≥5 points on the Upper Extremity Fugl-Meyer from baseline to final evaluation (at the end of training). Setting: General community. Participants: Anticipated enrollment of community-dwelling adults with chronic stroke (N=96; onset≥6mo) and moderate to severe residual hemiparesis of the upper limb as defined by a score of 10-45 points on the Upper Extremity Fugl-Meyer. Intervention: The intervention is a form of repetitive task practice using a combination of robot-assisted therapy coupled with functional arm use in real-world tasks administered over 12 weeks. Main Outcome Measures: Upper Extremity Fugl-Meyer Assessment (primary outcome), Wolf Motor Function Test, Action Research Arm Test, Stroke Impact Scale, questionnaires on pain and expectancy, magnetic resonance imaging, transcranial magnetic stimulation, arm kinematics, accelerometry, and a saliva sample for genetic testing. Results: Methods for this trial are outlined, and an illustration of interindividual variability is provided by example of 2 participants who present similarly at baseline but achieve markedly different outcomes. Conclusion: This article presents the design, methodology, and rationale of an ongoing study to develop a predictive model of response to a standardized therapy for stroke survivors with chronic hemiparesis. Applying concepts from precision medicine to neurorehabilitation is practicable and needed to establish realistic rehabilitation goals and to effectively allocate resources. Keywords: Magnetic resonance imaging, Prognosis, Rehabilitation, Stroke, Transcranial magnetic stimulation

Background. Robot-assisted therapy provides high-intensity arm rehabilitation that can significantly reduce stroke-related upper extremity (UE) deficits. Motor improvement has been shown at the joints trained, but generalization to real-world function has not been profound. Objective. To investigate the efficacy of robot-assisted therapy combined with therapist-assisted task training versus robot-assisted therapy alone on motor outcomes and use in participants with moderate to severe chronic stroke-related arm disability. Methods. This was a single-blind randomized controlled trial of two 12-week robot-assisted interventions; 45 participants were stratified by Fugl-Meyer (FMA) impairment (mean 21 ± 1.36) to 60 minutes of robot therapy (RT; n = 22) or 45 minutes of RT combined with 15 minutes therapist-assisted transition-to-task training (TTT; n = 23). The primary outcome was the mean FMA change at week 12 using a linear mixed-model analysis. A subanalysis included the Wolf Motor Function Test (WMFT) and Stroke Impact Scale (SIS), with significance P

BACKGROUND Historically, hemorrhage has been attributed as the leading cause (40%) of early death. However, a rigorous, real-time classification of the cause of death (COD) has not been performed. This study sought to prospectively adjudicate and classify COD to determine the epidemiology of trauma mortality. METHODS Eighteen trauma centers prospectively enrolled all adult trauma patients at the time of death during December 2015 to August 2017. Immediately following death, attending providers adjudicated the primary and contributing secondary COD using standardized definitions. Data were confirmed by autopsies, if performed. RESULTS One thousand five hundred thirty-six patients were enrolled with a median age of 55 years (interquartile range, 32-75 years), 74.5% were male. Penetrating mechanism (n = 412) patients were younger (32 vs. 64, p < 0.0001) and more likely to be male (86.7% vs. 69.9%, p < 0.0001). Falls were the most common mechanism of injury (26.6%), with gunshot wounds second (24.3%). The most common overall primary COD was traumatic brain injury (TBI) (45%), followed by exsanguination (23%). Traumatic brain injury was nonsurvivable in 82.2% of cases. Blunt patients were more likely to have TBI (47.8% vs. 37.4%, p < 0.0001) and penetrating patients exsanguination (51.7% vs. 12.5%, p < 0.0001) as the primary COD. Exsanguination was the predominant prehospital (44.7%) and early COD (39.1%) with TBI as the most common later. Penetrating mechanism patients died earlier with 80.1% on day 0 (vs. 38.5%, p < 0.0001). Most deaths were deemed disease-related (69.3%), rather than by limitation of further aggressive care (30.7%). Hemorrhage was a contributing cause to 38.8% of deaths that occurred due to withdrawal of care. CONCLUSION Exsanguination remains the predominant early primary COD with TBI accounting for most deaths at later time points. Timing and primary COD vary significantly by mechanism. Contemporaneous adjudication of COD is essential to elucidate the true understanding of patient outcome, center performance, and future research. LEVEL OF EVIDENCE Epidemiologic, level II.

The purpose of this study was to survey teacher opinions of 14 potential obstacles to teaching in general education classes attended by students with autism spectrum disorder (ASD). The anonymous participant responses were received from 16 elementary school teachers, 60 middle school teachers, and 131 high school teachers. Participants completed a questionnaire in which they rated 14 items. Rating data were uploaded to STATA data analysis software. The Kruskal-Wallis (K-W) statistic was used to analyze and interpret the data. Results identified items that significantly discriminated among teachers of the three grade levels and show a difference in the perceptions of teachers at different grade levels for some obstacles. Teachers at the elementary school level generally perceived greater obstacles than teachers at the middle school level, who perceived greater obstacles than those at the high school level. The results can be considered by educators and service providers when identifying professional development topics and resources to assist educators and service providers in the provision of instruction to maximize the potential for academic and social success for students with ASD in general education settings.

Endotheliopathy of trauma is characterized by breakdown of the endothelial glycocalyx. Elevated biomarkers of endotheliopathy, such as serum syndecan-1 (Synd-1) ≥ 40 ng/mL, have been associated with increased need for transfusions, complications, and mortality. We hypothesized that severely injured trauma patients who exhibit elevated Synd-1 levels shortly after admission have an increased likelihood of developing sepsis.We analyzed a subset of patients from the Pragmatic, Randomized Optimal Platelet and Plasma Ratios (PROPPR) trial who survived at least 72 hours after hospital admission, and we determined elevated Synd-1 levels (≥ 40 ng/mL) 4 hours after hospital arrival. Sepsis was defined a priori as meeting systemic inflammatory response criteria and having a known or suspected infection. Univariate analysis was performed to identify variables associated with elevated Synd-1 levels and sepsis. Significant variables at a value of p0.2 in the univariate analysis were chosen by purposeful selection and analyzed in a mixed effects multivariate logistic regression model to account for the 12 different study sites.We included 512 patients. Of these, 402 (79%) had elevated Synd-1 levels, and 180 (35%) developed sepsis. Median Synd-1 levels at 4 hours after admission were 70 ng/dL (interquartile range [IQR] 36 to 157 ng/dL) in patients who did not develop sepsis, and 165 ng/dL [IQR 67 to 336 ng/dL] in those who did (p0.001). Adjusting for treatment arm and site, multivariable analyses revealed that elevated Synd-1 status, Injury Severity Score (ISS), and total blood transfused were significantly associated with an increased likelihood of developing sepsis.Elevated Synd-1 levels 4 hours after admission in severely injured adult trauma patients who survived the initial 72 hours after hospital admission are associated with subsequent sepsis.

Background Methotrexate is used in the treatment of Rheumatoid Arthritis, Juvenile Idiopathic Arthritis and other conditions such as Acute Lymphoblastic Leukaemia and psoriasis. It can be administered orally or by injection. With oral administration, methotrexate’s bitter taste may not be masked, particularly when tablets are crushed to facilitate dosing in paediatrics or patients who have difficulty swallowing tablets.1 This can lead to long term treatment adherence issues and inaccurate dosing, putting patients at risk of adverse reactions or inadequate efficacy. A palatable oral liquid presentation of methotrexate would facilitate more accurate dosing and potentially improve treatment adherence; however, methotrexate is difficult to formulate as an oral liquid due to taste, solubility and stability challenges. Despite these difficulties, a palatable, stable oral methotrexate solution has been developed. Objectives To develop a palatable, stable, oral methotrexate solution, which complies with EU requirements for development of paediatric products,2 to aid accurate dosing and treatment adherence. Methods During each of two single-dose (10 mg and 2.5 mg) bioequivalence studies of the test 2 mg/ml methotrexate oral solution with licenced tablets, 24 healthy male subjects were asked to comment on the oral solution’s taste, indicating whether it was: Bitter, Sour, Salty, Sweet, or No Obvious Taste and they could also leave a remark. In parallel to clinical studies, long term ICH stability studies at ambient conditions (25°C/60%RH) and in-use shelf life studies were conducted. Results All subjects in the 10 mg dose study reported the oral solution as sweet tasting. One subject also reported an aftertaste and strange smell. In the 2.5 mg dose study, all subjects except one reported the solution as sweet tasting. The remaining subject reported a ‘soothing’ taste. One subject reported it was also sour and another reported an aftertaste. Two subjects additionally commented that they liked the taste. Both studies demonstrated bioequivalence and a similar safety profile between the oral solution and tablets. The stability studies illustrated that the oral methotrexate solution utilised in these clinical studies was stable at ambient conditions for up to 20 months, including a 3 months in-use period. The oral solution has recently been granted a European Union marketing authorisation and is the first methotrexate oral solution to be authorised for treatment of polyarthritic Juvenile Idiopathic Arthritis in Europe. Conclusions A 2 mg/ml oral methotrexate solution, developed to improve treatment adherence and dose accuracy, is reported to have a palatable, sweet taste and can be stored long term at ambient conditions with a 3 months in-use period. References [1] 1. Vrignaud S, et al. Int J Pharm 2015;487(1−2):270−3. [2] EMA/CHMP/QWP/805880/2012Rev. 2 Acknowledgements The clinical studies were conducted at PAREXEL. The development work was conducted at Quay Pharmaceuticals. Disclosure of Interest J.-A. Penton Employee of: Therakind Ltd, J. Winslade Shareholder of: Therakind Ltd, Employee of: Therakind Ltd, D. Roberts Employee of: Therakind Ltd, S. Conroy Shareholder of: Therakind Ltd, Employee of: Therakind Ltd

BackgroundComplicationsafter injury, such as acute respiratory distress syndrome (ARDS), are common aftertraumatic brain injury (TBI) and associated with poor clinical outcomes. The mechanisms driving non-neurologic organ dysfunction after TBI are not well understood. Tissue inhibitor of matrix metalloproteinase-3 (TIMP-3) is a regulator of matrix metalloproteinase activity, inflammation, and vascular permeability, and hence has plausibility as a biomarker for the systemic response to TBI.MethodsIn a retrospective study of 182 patients with severe isolated TBI, we measured TIMP-3 in plasma obtained on emergency department arrival. We used non-parametric tests and logistic regression analyses to test the association of TIMP-3 with the incidence of ARDS within 8 days of admission and in-hospital mortality.ResultsTIMP-3 was significantly higher among subjects who developed ARDS compared with those who did not (median 2810 pg/mLvs.2260 pg/mL, p=0.008), and significantly higher among subjects who died than among those who survived to discharge (median 2960 pg/mLvs.2080 pg/mL, p

BACKGROUND: Unconscious patients who present after being "found down" represent a unique triage challenge. These patients are selected for either trauma or medical evaluation based on limited information and have been shown in a single-center study to have significant occult injuries and/or missed medical diagnoses. We sought to further characterize this population in a multicenter study and to identify predictors of mistriage. METHODS: The Western Trauma Association Multicenter Trials Committee conducted a retrospective study of patients categorized as found down by emergency department triage diagnosis at seven major trauma centers. Demographic, clinical, and outcome data were collected. Mistriage was defined as patients being admitted to a non-triage-activated service. Logistic regression was used to assess predictors of specified outcomes. RESULTS: Of 661 patients, 33% were triaged to trauma evaluations, and 67% were triaged to medical evaluations; 56% of all patients had traumatic injuries. Trauma-triaged patients had significantly higher rates of combined injury and a medical diagnosis and underwent more computed tomographic imaging; they had lower rates of intoxication and homelessness. Among the 432 admitted patients, 17% of them were initially mistriaged. Even among properly triaged patients, 23% required cross-consultation from the non-triage-activated service after admission. Age was an independent predictor of mistriage, with a doubling of the rate for groups older than 70 years. Combined medical diagnosis and injury was also predictive of mistriage. Mistriaged patients had a trend toward increased late-identified injuries, but mistriage was not associated with increased length of stay or mortality. CONCLUSION: Patients who are found down experience significant rates of mistriage and triage discordance requiring cross-consultation. Although the majority of found down patients are triaged to nontrauma evaluation, more than half have traumatic injuries. Characteristics associated with increased rates of mistriage, including advanced age, may be used to improve resource use and minimize missed injury in this vulnerable patient population. LEVEL OF EVIDENCE: Epidemiologic study, level III. Language: en

Background. It has been observed that trauma patients often display an elevated procoagulant activity. This activity has been hypothesized to be caused in part by tissue factor (TF) located on the endothelium, blood cells and microparticles. We also observed in our previous studies that trauma patients with thermal, blunt and penetrating injuries have active FIXa and FXIa in their plasma, often persistent for several days to weeks. What is not known is the effect of injury type and severity on TF release after trauma. In the current study we evaluated how the severity of an injury with or without accompanying shock affects the frequency and concentration of TF, FIXa and FXIa in plasma from trauma patients. Methods. Eighty trauma patients presenting to a major urban level 1 trauma center (47 with blunt trauma and 33 with penetrating trauma) were enrolled. 62 patients were male and 18 female. The age of patients varied between 18 and 90 years (average 42.6±19.2 years) and the Injury Severity Score (ISS) varied between 1 and 75 (average 19.3±17.2). Blood was collected immediately upon emergency department arrival prior to any resuscitation or blood product transfusion. For analysis our cohort was divided into 4 groups (20 patients/group) based on their ISS and presence of shock (base deficit BD): Group 1: Non-severe injury, no shock (ISS≤15; BD>-6) Group 2: Non-severe injury, with shock (ISS≤15; BD≤-6) Group 3: Severe injury, no shock (ISS>15; BD>-6) Group 4: Severe injury, with shock (ISS>15; BD≤-6) Citrate plasma was prepared, frozen and stored at -80°C. No additional freeze/thaw cycles were involved prior to FXIa, FIXa and TF activity assays. The assays were based on a response of thrombin generation to corresponding monoclonal inhibitory antibodies (αFXIa-2, αFIXa-91 and αTF-5, respectively; all at 0.1 mg/mL). Results. The frequency of TF in less injured patients was relatively low (table) and increased by at least 3-fold in patients with severe injury (groups 3 and 4). The concentration of TF varied in a wide range in all 4 groups, but was the lowest in group 1 patient samples and the highest in groups 3 and 4. FXIa was observed in 91% of plasma samples and was high in all 4 groups of patients. Similar to TF, the concentration of FXIa varied in a wide range in the entire study population. Unlike TF however, FXIa was present in patients with shock at a higher concentration and did not correlate with the severity of injury. Only 9 of 20 group 1 plasma samples had detectable FIXa, whereas in groups 2-4 only 1 or 2 plasma samples had no FIXa activity. The median concentration of this protein varied in a relatively narrow range between all 4 groups, although the lowest was observed in group 1. For the entire cohort, there was a good correlation between FIXa and FXIa concentrations (R2 =0.33), but no correlation between TF and FIXa or FIXa. These data suggest that FXIa in trauma patient blood is generated primarily through the contact pathway, although the input of the TF pathway to FXI activation cannot be excluded. Table 1.Patient GroupTFFXIaFIXaFrequencyConcentration (pM)FrequencyConcentration (pM)FrequencyConcentration (pM)RangeMedianRangeMedianRangeMedian14/20 (20%)0.1 - >6.40.2818/20 (90%)0.9 - >647.39/20 (45%)73 - >100017523/20 (15%)0.5 - >6.41.0019/20 (95%)3.2- >6423.418/20 (90%)38 - >1000270312/20 (60%)0.3 - >6.43.5017/20 (85%)0.7 - >6411.118/20 (90%)75 - >1000252414/20 (70%)0.2 - >6.42.4819/20 (95%)1.8 - >6426.519/20 (95%)26 - >1000205Overall33/80 (41%)0.1 - >6.41.0173/80 (91%)0.7 - >10017.064/80 (80%)26 - >1000250 Conclusions. 1) Frequency and concentration of TF is higher in patients with a higher trauma severity, but it is independent of shock; 2) The vast majority of plasma samples from trauma patients contain active FIXa and FXIa; 3) Concentration of FXIa is higher in patients with shock and does not appear to be affected by the trauma severity. Taken together, these data suggest separate mechanisms for contact pathway activation after injury driven by shock and TF pathway activation driven by tissue injury. Disclosures No relevant conflicts of interest to declare.

Introduction Physical rehabilitation is one of the few non-pharmaceutical therapies for maintaining or improving walking ability for patients with multiple sclerosis. However, travel distance to rehabilitation clinics, neurological disability and insurance coverage often limit access to specialised rehabilitation services. To address these issues, we utilised a web-based system to support a home-based self-directed exercise programme. Methods Patients ( n = 24) were randomised to either routine home rehabilitation or to the multiple sclerosis home automated tele-management system for a six-month period. The study group had a mean age of 50.4 years, 56% of patients were male, and 67% had progressive multiple sclerosis with an overall mean Patient Determined Disease Steps score of 4.4 (cane or crutch required for walking). Key outcomes included the timed 25-foot-walk, six-minute-walk and the Berg Balance Scale. Results There was no statistically significant difference in the change of the primary walking outcome measure, timed 25-foot-walk, at six months between the home automated tele-management intervention and control groups ( p = 0.44). Similarly, change scores for the six-minute-walk were not significantly different between the home automated tele-management or control groups at six months. Discussion Maintaining overall gait abilities in this group of predominantly progressive multiple sclerosis patients is notable. Exercise adherence was positively associated with higher multiple sclerosis disability and self-reported walking ability. Study engagement and participation in routine home-based exercise for the entire study period was challenging. Further research using clinical video telerehabilitation techniques that optimise patient involvement warrants further study.

BACKGROUND Acute traumatic coagulopathy affects 20% to 30% of trauma patients, but the extensive collinearity of the coagulation cascade complicates attempts to clarify global clotting factor dysfunction. This study aimed to characterize phenotypes of clotting factor dysfunction and their contributions to mortality after major trauma. METHODS This prospective cohort study examines all adult trauma patients of the highest activation level presenting to San Francisco General Hospital between February 2005 and February 2015. Factors II, V, VII, VIII, IX, and X and protein C activity on admission and mortality status at 28 days were assessed. Predictors of 28-day mortality in univariate analysis were included in multiple logistic regression controlling for traumatic brain injury (TBI), acidosis, age, and mechanism of injury. Principal component analysis was utilized to identify phenotypic coagulation. RESULTS Complete coagulation factor data were available for 876 (61%) of 1,429 patients. In multiple logistic regression, factors V (odds ratio [OR], 0.86; 95% confidence interval [CI], 0.76-0.97), VIII (OR, 0.97; 95% CI, 0.95-0.99), and X (OR, 0.79; 95% CI, 0.68-0.92) and protein C (OR, 1.17; 95% CI, 1.05-1.30) significantly predicted 28-day mortality after controlling for age, base deficit, mechanism of injury, and TBI. Principal component analysis identified two significant principal components (Phenotypes 1 and 2) that accounted for 66.3% of the total variance. Phenotype 1 (factors II, VII, IX, and X and protein C abnormalities) explained 49.3% and was associated with increased injury, coagulopathy, TBI, and mortality. Phenotype 2 (factors V and VIII abnormalities) explained 17.0% and was associated with increased coagulopathy, blunt injury, and mortality. Only Phenotype 2 remained significantly associated with 28-day mortality in multiple logistic regression. CONCLUSIONS Principal component analysis identified two distinct phenotypes within the entirety of global clotting factor abnormalities, and these findings substantiate the crucial association of factors V and VIII on mortality following trauma. This may be the first step toward identifying unique phenotypes after injury and personalizing hemostatic resuscitation. LEVEL OF EVIDENCE Prognostic study, level III.

Background Recent studies have demonstrated the vital influence of commensal microbial communities on human health. The central role of the gut in the response to injury is well described; however, no prior studies have used culture-independent profiling techniques to characterize the gut microbiome after severe trauma. We hypothesized that in critically injured patients, the gut microbiome would undergo significant compositional changes in the first 72 hours after injury. Methods Trauma stool samples were prospectively collected via digital rectal examination at the time of presentation (0 hour). Patients admitted to the intensive care unit (n=12) had additional stool samples collected at 24 hours and/or 72 hours. Uninjured patients served as controls (n=10). DNA was extracted from stool samples and 16S rRNA-targeted PCR amplification was performed; amplicons were sequenced and binned into operational taxonomic units (OTUs; 97% sequence similarity). Diversity was analyzed using principle coordinates analyses, and negative binomial regression was used to determine significantly enriched OTUs. Results Critically injured patients had a median Injury Severity Score of 27 and suffered polytrauma. At baseline (0 hour), there were no detectable differences in gut microbial community diversity between injured and uninjured patients. Injured patients developed changes in gut microbiome composition within 72 hours, characterized by significant alterations in phylogenetic composition and taxon relative abundance. Members of the bacterial orders Bacteroidales, Fusobacteriales and Verrucomicrobiales were depleted during 72 hours, whereas Clostridiales and Enterococcus members enriched significantly. Discussion In this initial study of the gut microbiome after trauma, we demonstrate that significant changes in phylogenetic composition and relative abundance occur in the first 72 hours after injury. This rapid change in intestinal microbiota represents a critical phenomenon that may influence outcomes after severe trauma. A better understanding of the nature of these postinjury changes may lead to the ability to intervene in otherwise pathological clinical trajectories. Level of evidence III Study type Prognostic/epidemiological

BACKGROUND Acute respiratory distress syndrome (ARDS) is common after traumatic brain injury (TBI) and is associated with worse neurologic outcomes and longer hospitalization. However, the incidence and associated causes of ARDS in isolated TBI have not been well studied. METHODS We performed a subgroup analysis of 210 consecutive patients with isolated severe TBI enrolled in a prospective observational cohort at a Level 1 trauma center between 2005 and 2014. Subjects required endotracheal intubation and had isolated severe TBI defined by a head Abbreviated Injury Scale (AIS) score of 3 or greater and AIS score lower than 3 in all other categories. ARDS within the first 8 days of admission was rigorously adjudicated using Berlin criteria. Regression analyses were used to test the association between predictors of interest and ARDS. RESULTS The incidence of ARDS in the first 8 days after severe isolated TBI was 30%. Patients who developed ARDS were administered more crystalloids (4.3 L vs. 3.5 L, p = 0.005) and blood products in the first 12 hours of admission. Patients with ARDS had significantly worse clinical outcomes measured at 28 days, including longer median intensive care unit and hospital stays (4 days vs. 13 days, p < 0.001, and 7.5 days vs. 14.5 days, p < 0.001, respectively). In unadjusted logistic regression analyses, the odds of developing ARDS were significantly associated with head AIS score (odds ratio [OR], 1.8; p = 0.018), male sex (OR, 2.9; p = 0.012), and early transfusion of platelets (OR, 2.8; p = 0.003). These associations were similar in a multivariate logistic regression model. CONCLUSION In the era of balanced hemostatic resuscitation practices, severity of head injury, male sex, early crystalloids, and early transfusion of platelets are associated with a higher risk of ARDS after severe isolated TBI. Early transfusion of platelets after severe TBI may be a modifiable risk factor for ARDS, and these findings invite further investigation into causal mechanisms driving this observed association. LEVEL OF EVIDENCE Prognostic/epidemiologic study, level III.

BACKGROUND: Robots designed for rehabilitation of the upper extremity after stroke facilitate high rates of repetition during practice of movements and record precise kinematic data, providing a method to investigate motor recovery profiles over time.OBJECTIVE: To determine how motor recovery profiles during robotic interventions provide insight into improving clinical gains.METHODS: A convenience sample (n = 22), from a larger randomized control trial, was taken of chronic stroke participants completing 12 sessions of arm therapy. One group received 60 minutes of robotic therapy (Robot only) and the other group received 45 minutes on the robot plus 15 minutes of translation-to-task practice (Robot + TTT). Movement time was assessed using the robot without powered assistance. Analyses (ANOVA, random coefficient modeling [RCM] with 2-term exponential function) were completed to investigate changes across the intervention, between sessions, and within a session.RESULTS: Significant improvement (P < .05) in movement time across the intervention (pre vs post) was similar between the groups but there were group differences for changes between and within sessions (P < .05). The 2-term exponential function revealed a fast and slow component of learning that described performance across consecutive blocks. The RCM identified individuals who were above or below the marginal model.CONCLUSIONS: The expanded analyses indicated that changes across time can occur in different ways but achieve similar goals and may be influenced by individual factors such as initial movement time. These findings will guide decisions regarding treatment planning based on rates of motor relearning during upper extremity stroke robotic interventions.

BACKGROUND: Acute lung injury following trauma remains a significant source of morbidity and mortality. Although multiple trauma studies have used hypoxemia without radiographic adjudication as a surrogate for identifying adult respiratory distress syndrome (ARDS) cases, the differences between patients with hypoxemia alone and those with radiographically confirmed ARDS are not well described in the literature. We hypothesized that nonhypoxemic, hypoxemic, and ARDS patients represent distinct groups with unique characteristics and predictors. METHODS: Laboratory, demographic, clinical, and outcomes data were prospectively collected from 621 intubated, critically injured patients at an urban Level 1 trauma center from 2005 to 2013. Hypoxemia was defined as PaO2/FIO2 ratio of 300 or lower. ARDS was adjudicated using Berlin criteria, with blinded two-physician consensus review of chest radiographs. Group comparisons were performed by hypoxemia and ARDS status. Logistic regression analyses were performed to separately assess predictors of hypoxemia and ARDS. RESULTS: Of the 621 intubated patients, 64% developed hypoxemia; 46% of these hypoxemic patients developed ARDS by chest radiograph. Across the three groups (no hypoxemia, hypoxemia, ARDS), there were no significant differences in age, sex, or comorbidities. However, there was an increase in severity of shock, injury, and chest injury by group, with corresponding trends in transfusion requirements and volume of early fluid administration. Outcomes followed a similar stepwise pattern, with pneumonia, multiorgan failure, length of intensive care unit stay, number of ventilator days, and overall mortality highest in ARDS patients. In multiple logistic regression, early plasma transfusion, delayed crystalloid administration, body mass index, and head and chest injury were independent predictors of hypoxemia, while head and chest injury, early crystalloid infusion, and delayed platelet transfusion were independent predictors of ARDS. CONCLUSION: Hypoxemia and ARDS exist on a spectrum of respiratory dysfunction following trauma, with increasing injury severity profiles and resuscitation requirements. However, they also represent distinct clinical states with unique predictors, which require directed research approaches and targeted therapeutic strategies. LEVEL OF EVIDENCE: Prognostic and epidemiologic study, level III. Language: en

MIT’s motto is “Mens et Manus” (Mind and Hand), and we have adopted it as the guiding rule (principle) for our line of research: using robotics and information technology to reconnect the brain to the hand. Nurture allows a patient to reduce impairment, increase function, and improve the quality of life beyond natural recovery. This chapter describes our efforts toward this goal since the initial development of the MIT-Manus in 1989. Numerous clinical trials involving thousands of patients (subjects) working with (receiving therapy using) the commercial version of the MIT-Manus have been conducted since then, and we have created a complete robotic gym for the upper extremity. Recently, the American Heart Association and the Veterans Affairs/Department of Defense endorsed the use of robot-assisted therapy in stroke rehabilitation for upper extremity, and we have been focusing on how to tailor therapy to a particular patient’s need and in determining who is a responder (and no-responder) to this kind of intervention.

Conroy SS, Whitall J, Dipietro L, Jones-Lush LM, Zhan M, Finley MA, Wittenberg GF, Krebs HI, Bever CT. Effect of gravity on robot-assisted motor training after chronic stroke: a randomized trial. Objectives To determine the efficacy of 2 distinct 6-week robot-assisted reaching programs compared with an intensive conventional arm exercise program (ICAE) for chronic, stroke-related upper-extremity (UE) impairment. To examine whether the addition of robot-assisted training out of the horizontal plane leads to improved outcomes. Design Randomized controlled trial, single-blinded, with 12-week follow-up. Setting Research setting in a large medical center. Participants Adults (N=62) with chronic, stroke-related arm weakness stratified by impairment severity using baseline UE motor assessments. Interventions Sixty minutes, 3 times a week for 6 weeks of robot-assisted planar reaching (gravity compensated), combined planar with vertical robot-assisted reaching, or intensive conventional arm exercise program. Main Outcome Measure UE Fugl-Meyer Assessment (FMA) mean change from baseline to final training. Results All groups showed modest gains in the FMA from baseline to final with no significant between group differences. Most change occurred in the planar robot group (mean change ± SD, 2.94±0.77; 95% confidence interval [CI], 1.40–4.47). Participants with greater motor impairment (n=41) demonstrated a larger difference in response (mean change ± SD, 2.29±0.72; 95% CI, 0.85–3.72) for planar robot-assisted exercise compared with the intensive conventional arm exercise program (mean change ± SD, 0.43±0.72; 95% CI, –1.00 to 1.86). Conclusions Chronic UE deficits because of stroke are responsive to intensive motor task training. However, training outside the horizontal plane in a gravity present environment using a combination of vertical with planar robots was not superior to training with the planar robot alone.

Background Effective rehabilitative therapies are needed for patients with long-term deficits after stroke. Methods In this multicenter, randomized, controlled trial involving 127 patients with moderate-to-severe upper-limb impairment 6 months or more after a stroke, we randomly assigned 49 patients to receive intensive robot-assisted therapy, 50 to receive intensive comparison therapy, and 28 to receive usual care. Therapy consisted of 36 1-hour sessions over a period of 12 weeks. The primary outcome was a change in motor function, as measured on the Fugl-Meyer Assessment of Sensorimotor Recovery after Stroke, at 12 weeks. Secondary outcomes were scores on the Wolf Motor Function Test and the Stroke Impact Scale. Secondary analyses assessed the treatment effect at 36 weeks. Results At 12 weeks, the mean Fugl-Meyer score for patients receiving robot-assisted therapy was better than that for patients receiving usual care (difference, 2.17 points; 95% confidence interval [CI], −0.23 to 4.58) and worse than ...

Fragile X syndrome and other trinucleotide diseases are characterized by an elongation of a repeating DNA triplet. The ensemble-averaged lambda exonuclease digestion rate of different substrates, including one with an elongated FMR1 gene containing 120 CGG repeats, was measured using absorption and fluorescence spectroscopy. By use of magnetic tweezers sequence-dependent digestion rates and pausing was measured for individual lambda exonucleases. Within the triplet repeats a lower average and narrower distribution of rates and a higher frequency of pausing was observed.

To examine successful Canadian nursing and health promotion intervention programmes for childhood obesity prevention during gestation and infancy, an integrative review was performed of the literature from 1980 to September 2005. The following databases were used: PubMed; Cochrane Database of Systematic Reviews; Cochrane Controlled Trials Register; Database of Abstracts of Reviews of Effects; ACP Journal Club; MEDLINE; EMBASE; CINAHL; Web of Science; Scopus; Sociological Abstracts; Sport Discus; PsycInfo; ERIC and HealthStar. MeSH headings included: infancy (0-24 months), gestation, gestational diabetes, nutrition, prenatal care, pregnancy, health education, pregnancy outcome, dietary services with limits of Canadian, term birth. Of 2028 articles found, six Canadian childhood obesity prevention programmes implemented during gestation and/or infancy were found; three addressed gestational diabetes with five targeting low-income Canadian urban and/or Aboriginal populations. No intervention programmes specifically aimed to prevent childhood obesity during gestation or infancy. This paucity suggests that such a programme would be innovative and much needed in an effort to stem the alarming increase in obesity in children and adults. Any attempts either to develop new approaches or to replicate interventions used with obese adults or even older children need careful evaluation and pilot testing prior to sustained use within the perinatal period.

Introduction Measurement of faecal calprotectin (FC) may identify those harbouring inflammatory bowel disease (IBD). Use of the test is supported by NICE guidance (DG11) but evidence of its performance, in “real-life”, in patients presenting to primary care, is limited. Aim To assess the yield of IBD from FC testing in primary care. Method FC testing (Immunodiagnostics Phical Calprotectin ELISA) was made available to clinicians in October 2013. The results of all FC assays from 1.10.13 to 28.2.14 were reviewed retrospectively with results of GI investigations. Results Of FC measurements undertaken in 526 patients, 26 could not be identified on the local patient administration system, 57 were initiated in secondary care, 23 had known IBD and outcomes were not available for 22 patients with a raised FC (median 90 μg/g); range 54–995). These were excluded. 398 patients had FC requested in primary care (158 male; median age 42; range 6–91). FC was “positive” (>50 μg/g) in 132/398 (33.2%; median age 44 (range 6–91); median FC 128.5 μg/g (51–1770). 122/132 with positive FC underwent further investigation; 94 (77%) had lower GI endoscopy: IBD (7), colorectal cancer (2), adenoma (8), nil significant (77). 87/94 had lower GI endoscopy for a false positive FC (no IBD). 49/266 FC-negative patients also underwent lower GI endoscopy (median age 47; range 19–76) finding IBD (2), diverticulitis (1), adenomas (2), nil significant (43). 3/266 FC negative patients had IBD. IBD was diagnosed in 11/398 (2.3%; 4 ulcerative colitis (UC), 3 Crohn’s disease (CD), 2 collagenous colitis, 2 lymphocytic colitis (Table 1)). 8/11 were FC positive (range 67–1170); 3 were FC negative. At a 50 μg/g threshold, sensitivity for detecting IBD was 72.7%, specificity 68%, positive predictive value (PPV) 6.1%, negative predictive value 98.9%. Conclusion FC testing in primary care has lower sensitivity and specificity than in secondary care and poor PPV for detecting IBD. False positive FC is associated with more lower GI investigation than previously estimated. This experience differs from data used to inform NICE DG11. Strategies to target use to those with higher pre-test probability of IBD are needed. Disclosure of interest S. Conroy: None Declared, M. Hale: None Declared, S. Cross: None Declared, K. Swallow: None Declared, R. Sidhu: None Declared, R. Sargur: None Declared, A. Lobo Consultant for: Takeda UK and Vifor Pharma.

BACKGROUND: Trauma is the leading cause of death in individuals under the age of 44. Acute traumatic coagulopathy (ATC) occurs when severe injury is combined with shock and results in a hypocoagulable state resulting in increased bleeding, increased resuscitation requirements and worsened outcomes including a 4-fold increase in mortality. Our group has implicated protein C activation as a likely mechanism for ATC. We have evaluated whether activated protein C (APC) induces coagulopathy through cleavage of factor (f)V/Va by systematically evaluating 4 groups of increasing level of traumatic coagulopathy. METHODS: From a large cohort of plasma samples collected from trauma patients at time of admission to a major level 1 trauma sample, 80 plasma samples distributed equally between the following trauma severity groupings were selected: Group 1: ISS ≤ 15 and BD > -6 (less injured, no shock); Group 2: ISS ≤ 15 and BD ≤ -6 (less injured, with shock); Group 3:ISS > 15 and BD > -6 (more injured, no shock); Group 4:ISS > 15 and BD ≤ -6 (more injured, with shock). Each plasma sample was evaluated for plasma composition (functional activity of fII, fV, fVII, fVIII, fIX, fX, antithrombin, tissue factor pathway inhibitor, protein C), plasmin-antiplasmin complex (PAP), α-thrombin-antithrombin complex (TAT), and mathematically modeled thrombin generation. Quantitative Western blot analyses were performed using an anti-fV antibody directed at the fV heavy chain (residues 307-506). Intact fV levels were quantified via densitometry to determine whether levels were the within range characterizing healthy individuals and the presence of APC derived and other degradation products assessed via mobility comparison to purified standards. Demographic, resuscitation, and outcomes data were collected in parallel. RESULTS: All data were quantitated and evaluated for having concentrations above and/or below the normal range for each analyte. For PAP, Groups 3 (18/20) and 4 (17/20) had a greater percentage of individuals over Groups 1 (5/20) and 2 (6/20) that were above the normal range. Groups 3 (12/20) and 4 (12/20) also had a higher percentage of detectable α-TAT over Groups 1 (5/20) and 2 (2/20). For fV antigen, Group 4 had 16/20 individuals that were below the lower limit of normal. Groups 1, 2 and 3 were all similar with 5/20 below the limit of normal but had 3-5/20 above the upper limit of normal. Products associated with activated protein C were found (fV 30kD fragment) but also other cleavage products not associated with APC were observed. There was more fV fragmentation in Group 4, with the 30kD fragment being detected in 10 individuals. No detectable fV 30kD fragments were detected in either Groups 1 or 2. In terms of the overall plasma composition there is a large variation in functional activity, especially fVIII. Group 4 showed a pattern of all factors reduced except for TFPI versus Groups 1,2, 3. These pro and anticoagulant differences between individuals results in heterogenous modeled thrombin generation profiles with the majority all being procoagulant versus a normal control. Group 4 had a higher percentage of individuals that had a prolonged clot time and a pattern towards diminished thrombin generation. CONCLUSIONS: These data suggest that the combination of injury and shock were associated with altered PAP, TAT and functional activity changes of the plasma composition resulting in hemorrhagic thrombin generation profiles. In addition the most severely injured and shocked patients had less fVa activity, less intact fV and increased degradation of fV/fVa suggesting the presence of increased APC activity in mediating ATC. Disclosures No relevant conflicts of interest to declare.

Purpose Emergency Medical Services (EMS) personnel perform pre-hospital triage of pediatric emergencies. Standing orders and on-line medical direction provide triage guidelines to determine the level of care required by the patient during ambulance transport. Children with special healthcare needs (CSHCN) have been identified as a unique sub-group of pediatric emergencies. The purpose of this study is to characterize the level of care required by CSHCN during ambulance transport and identify a correlation between this level of care and subsequent hospital admission. Hypothesis We assessed the hypothesis that CSHCN with emergencies requiring Advanced Life Support (ALS) transport are more likely to be admitted to the receiving hospital compared to children requiring Basic Life Support (BLS) transport. Methods CSHCN were defined as children, 21 years of age or younger, with a congenital or acquired condition or chronic physical or mental illness, affecting physical or mental growth and development. During a 22-month period, 1,697 EMS responses for CSHCN were identified and evaluated for the nature of the emergency, level of care required during transport, and admission status. Results 71% of CSHCN required ALS transport. Medical emergencies were twice as likely to result in hospital admission compared to traumatic emergencies (1.25≤OR≤3.04, p≤0.01). For all emergencies, children requiring ALS transport were 4.5 times more likely to be admitted to the hospital compared to those requiring BLS transport (2.74≤OR≤7.73, p≤0.01). When excluding emergencies directly related to the child9s special need, children requiring ALS transport were 7.63 times more likely to be admitted to the hospital compared to those requiring BLS transport (3.48≤OR≤17.14, p≤0.01). Conclusions This study shows a significant correlation between level of transport and hospital admission in the studied population, suggesting that current pre-hospital triage protocols correctly identify CSHCN who require a more advanced or specialized level of care.