Implementation of active injury management (AIM) in youth with acute concussion: A randomized controlled trial.

BACKGROUND: Nearly 2 million youth seek acute medical care following concussion in the U.S. each year. Current standard of care recommends rest for the first 48 h after a concussion. However, research suggests that prolonged rest may lengthen recovery time especially for patients with certain risk profiles. Research indicates that physical activity and behavioral management interventions (sleep, stress management) may enhance recovery. To date, there is limited empirical evidence to inform acute (<72 h) concussion recommendations for physical activity and behavioral management in adolescents. OBJECTIVE: To determine the effectiveness of physical activity and behavioral management for acute concussion in adolescents and young adults, and to evaluate the role of patient characteristics on treatment response. METHODS: This multicenter prospective randomized controlled trial will determine which combination of physical activity and behavioral management is most effective for patients 11-24 years old who present to the emergency department or concussion clinic within 72 h of injury. Participants are randomized into: 1) rest, 2) physical activity, 3) mobile health application (mHealth) behavioral management, or 4) physical activity and mHealth app conditions. Assessments at enrollment, 3-5 days, 14 days, 1 month, and 2 months include: concussion symptoms, balance, vestibular-ocular and cognitive assessments, quality of life, and recovery time. Somatic symptoms and other risk factors are evaluated at enrollment. Compliance with treatment and symptoms are assessed daily using actigraph and daily self-report. The primary study outcome is symptoms at 14 days. CONCLUSION: Prescribed physical activity and behavioral management may improve outcomes in youth following acute concussion.

Association between triglyceride and high-density lipoprotein cholesterol change following fibrate therapy.

BACKGROUND: Debate surrounding the role of fibrates has followed mixed outcomes from several randomised controlled trials. Subgroup analysis of even the negative trials reveals significant reduction in cardiovascular risk amongst patients with low HDL-C and high TG. We previously described factors associated with HDL-C change following fibrates. As fibrates influence both HDL-C and TG levels via their action on PPAR-α, we now wished to study TG change following fibrate therapy and any associations with baseline and change in HDL-C and TC levels. METHODS: Data was collected from case notes of patients started on fibrates (n=248) between 2002 and 2008 in the lipid clinics at Heart of England NHS Foundation Trust. Regression analyses were carried out to determine factors associated with changes in TG. RESULTS: Multiple regression analysis revealed that TG change was associated with pre-treatment TG (p<0.001) and TC levels (p=0.029). The association between TG change and pre-treatment TG remained significant when all factors including gender, concurrent statin treatment, diabetes and baseline HDL-C were entered into the regression model. Our previous study demonstrated significant post-fibrate HDL-C change in the group with baseline HDL-C values <1.0mmol/l. In our present study significant TG reduction was observed regardless of the baseline patient characteristics including HDL-C levels. CONCLUSIONS: The actions of fibrates are considered to be mediated via PPAR-α, but our data suggest that the effects on TG and HDL-C are different. Thus, the mechanisms mediating the changes of these lipids following fibrate treatment may vary.

Brain activation during neurocognitive testing using functional near-infrared spectroscopy in patients following concussion compared to healthy controls.

There is no accepted clinical imaging modality for concussion, and current imaging modalities including fMRI, DTI, and PET are expensive and inaccessible to most clinics/patients. Functional near-infrared spectroscopy (fNIRS) is a non-invasive, portable, and low-cost imaging modality that can measure brain activity. The purpose of this study was to compare brain activity as measured by fNIRS in concussed and age-matched controls during the performance of cognitive tasks from a computerized neurocognitive test battery. Participants included nine currently symptomatic patients aged 18-45 years with a recent (15-45 days) sport-related concussion and five age-matched healthy controls. The participants completed a computerized neurocognitive test battery while wearing the fNIRS unit. Our results demonstrated reduced brain activation in the concussed subject group during word memory, (spatial) design memory, digit-symbol substitution (symbol match), and working memory (X's and O's) tasks. Behavioral performance (percent-correct and reaction time respectively) was lower for concussed participants on the word memory, design memory, and symbol match tasks than controls. The results of this preliminary study suggest that fNIRS could be a useful, portable assessment tool to assess reduced brain activation and augment current approaches to assessment and management of patients following concussion.

Non-newtonian and flow pulsatility effects in simulation models of a stented intracranial aneurysm.

Three models of different stent designs implanted in a cerebral aneurysm, originating from the Virtual Intracranial Stenting Challenge '07, are meshed and the flow characteristics simulated using commercial computational fluid dynamics (CFD) software in order to investigate the effects of non-Newtonian viscosity and pulsatile flow. Conventional mass inflow and wall shear stress (WSS) output are used as a means of comparing the CFD simulations. In addition, a WSS distribution is presented, which clearly discriminates in favour of the stent design identified by other groups. It is concluded that non-Newtonian and pulsatile effects are important to include in order to avoid underestimating wss, to understand dynamic flow effects, and to discriminate more effectively between stent designs.

Multi-scale interaction of particulate flow and the artery wall.

We discuss, from the perspective of basic science, the physical and biological processes which underlie atherosclerotic (plaque) initiation at the vascular endothelium, identifying the widely separated spatial and temporal scales which participate. We draw on current, related models of vessel wall evolution, paying particular attention to the role of particulate flow (blood is not a continuum fluid), and proceed to propose, then validate all the key components in a multiply-coupled, multi-scale modeling strategy (in qualitative terms only, note). Eventually, this strategy should lead to a quantitative, patient-specific understanding of the coupling between particulate flow and the endothelial state.

Modelling the interaction of haemodynamics and the artery wall: current status and future prospects.

Clinical research has historically focused on the two main strategies of in vivo and in vitro experimentation. The concept of applying scientific theory to direct clinical applications is relatively recent. In this paper we focus on the interaction of wall shear stress with the endothelium and discuss how 'state of the art' computer modelling techniques can provide valuable data to aid understanding. Such data may be used to inform experiment and further, may help identify the key features of this complex system. Current emphasis is on coupling haemodynamics with models of biological phenomena to test hypotheses or predict the likely outcome of a disease or an intervention. New technologies to enable the integration of models of different types, levels of complexity and scales, are being developed. As will be discussed, the ultimate goal is the translation of this technology to the clinical arena.

[The undetected brain lesion in sports. Minor traumatic brain injury and its sequelae]. / Die unerkannte Hirnverletzung im Sport. Das leichte Schädel-Hirn-Trauma und seine Folgen.

The minor traumatic brain injury (mTBI) in sports is often looked at as a bagatelle. The treating physician underestimates the severity of the injury suspecting that a mTBI is a nonstructural lesion with an overall excellent prognosis in the majority of the cases. This paper shows that the minor traumatic brain injury may be a structural brain lesion with potentially life-threatening dangers. The therapy should follow exactly defined guidelines, e.g., stepwise protocol of the Concussion in Sports (CIS-) Group. Return to sports activities should happen only when all physical but also cognitive symptoms have subsided. All mTBIs that have been sustained prior to the actual injury have to be recorded properly because repeated mTBIs may cause chronic degenerative brain damage. Neuropsychological testing will aid in the correct diagnosis of a mTBI and is a useful parameter in the course of the injury. In the future biochemical markers may serve as indicators of the severity of the brain injury and may also aid in predicting the outcome after TBI. Today biochemical markers do not serve as a substitute for neuroimaging.

No cumulative effects for one or two previous concussions.

BACKGROUND: Sports medicine clinicians and the general public are interested in the possible cumulative effects of concussion. OBJECTIVE: To examine whether athletes with a history of one or two previous concussions differed in their preseason neuropsychological test performances or symptom reporting. METHOD: Participants were 867 male high school and university amateur athletes who completed preseason testing with ImPACT version 2.0. They were sorted into three groups on the basis of number of previous concussions. There were 664 athletes with no previous concussions, 149 with one previous concussion, and 54 with two previous concussions. Multivariate analysis of variance was conducted using the verbal memory, visual memory, reaction time, processing speed, and postconcussion symptom composite scores as dependent variables and group membership as the independent variable. RESULTS: There was no significant multivariate effect, nor were there any significant main effects for individual scores. There was no measurable effect of one or two previous concussions on athletes' preseason neuropsychological test performance or symptom reporting. CONCLUSION: If there is a cumulative effect of one or two previous concussions, it is very small and undetectable using this methodology.

2-D mathematical models of Tumor-induced angiogenesis.

Angiogenesis, the formation of blood vessels from a pre-existing vasculature, is a process in which capillary sprouts are formed in response to externally supplied chemical stimuli. Tumor-induced angiogenesis plays a significant role in tumor's growth, metastasis, in which endothelia-cell is the most active member engaging in various stages, including the secretion and diffusion of various tumor-induced angiogenesis factors (TAF); the nascent endothelial cell migrates towards a particular direction and position under the interaction of a series of internal and external factors; eventually the new formed capillaries reach and penetrate the tumor. At present there is no technique of medical image to accurately investigate the micro-vessel net of tumor, it makes some hard in clinical treatment of tumor. In this paper we present a 2-D mathematical model, which takes into account essential endothelial cell-extra cellular matrix interactions, and the response to chemical stimuli (TAF) mentioned above, to describes the formation of the capillary sprout network in response to physiological conditions around tumor especially investigate the process inside tumor in terms of the complex features of tumor. This theoretical capillary networks generated by computer simulations provide a premise for the further research.

Effects of stents under asymmetric inflow conditions.

Patient-to-patient variations in artery geometry may determine their susceptibility to stenosis formation. These geometrical variations can be linked to variations in flow characteristics such as wall shear stress through stents, which increases the risk of restenosis. This paper considers computer models of stents in non-symmetric flows and their effects on flow characteristics at the wall. This is a fresh approach from the point of view of identifying a stent design whose performance is insensitive to asymmetric flow. Measures of dissipated energy and power are introduced in order to discriminate between competing designs of stents.

The assessment of sport-related concussion: the evidence behind neuropsychological testing and management.

Because of the lack of valid evidence to support the current recommendations for the management of mild traumatic brain injury (concussion), many physicians, athletic trainers, coaches, and athletes have called into question the way concussions are treated in athletics. This review article discusses the current evidence for the management of concussion in high school, college, and professional sports. A complete review of the epidemiologic and neuropsychological studies to date is presented and critically reviewed, as are other assessment and management tools in concussion. The appropriate use of neuropsychological testing, grading scales, and return-to-play recommendations are discussed in depth based on the current evidence. Additionally, areas requiring further research are identified and future trends are briefly discussed.

Does loss of consciousness predict neuropsychological decrements after concussion?

OBJECTIVE: To investigate the importance of loss of consciousness (LOC) in predicting neuropsychological test performance in a large sample of patients with head injury. DESIGN: Retrospective comparison of neuropsychological test results for patients who suffered traumatic LOC, no LOC, or uncertain LOC. SETTING: Allegheny General Hospital, Pittsburgh, Pennsylvania. PATIENTS: The total number of patients included in this study was 383. MAIN OUTCOME MEASURES: Neuropsychological test measures, including the visual reproduction, digit span, and logical memory subtests of the Wechsler memory scale (revised), the Trail Making test, Wisconsin Card Sorting test, Hopkins Verbal Learning test, Controlled Oral Word Association, and the Galveston Orientation and Amnesia test (GOAT). RESULTS: No significant differences were found between the LOC, no LOC, or uncertain LOC groups for any of the neuropsychological measures used. Patients who had experienced traumatic LOC did not perform more poorly on neuropsychological testing than those with no LOC or uncertain LOC. All three groups demonstrated mildly decreased performance on formal tests of speed of information processing, attentional process, and memory. CONCLUSION: The results of this study cast doubt on the importance of LOC as a predictor of neuropsychological test performance during the acute phase of recovery from mild traumatic brain injury. Neuropsychological testing procedures have been shown to be sensitive in measuring cognitive sequelae of mild traumatic brain injury (concussion) in athletes. The failure of this study to find any relationship between LOC and neuropsychological functioning in a large sample of patients with mild head trauma calls into question the assignment of primary importance to LOC in grading severity of concussion. This study also does not provide support for the use of guidelines that rely heavily on LOC in making return-to-play decisions. Continued research is necessary to determine the relative importance of markers of concussion in athletes.

Reconstruction of blood flow patterns in human arteries.

Local haemodynamic factors in large arteries are associated with the pathophysiology of cardiovascular diseases such as atherosclerosis and strokes. In search of these factors and their correlation with atheroma formation, quantitative haemodynamic data in realistic arterial geometry become crucial. At present no in vivo non-invasive technique is available that can provide accurate measurement of three-dimensional blood velocities and shear stresses in curved and branching sites of vessels where atherosclerotic plaques are found frequently. This paper presents a computer modelling technique which combines state-of-the-art computational fluid dynamics (CFD) with new noninvasive magnetic resonance imaging techniques to provide the complete haemodynamic data in 'real' arterial geometries. Using magnetic resonance angiographic and velocity images acquired from the aortic bifurcation of a healthy human subject, CFD simulations have been carried out and the predicted flow patterns demonstrate the non-planar-type flow characteristics found in experimental studies.

Flow in carotid bifurcations: effect of the superior thyroid artery.

The superior thyroid artery was ignored in previous fluid dynamics studies of carotid bifurcations. However, it is not clear to what extent the flow patterns within the carotid might be influenced by the presence of this outflow tract in reality. In this study, quantitative effects of the superior thyroid artery upon the flow patterns and wall shear stress in the carotid bifurcation were investigated in detail by a numerical simulation method. Comparisons of the maximum reversed flow velocities, flow patterns and wall shear stress were made between models with and without the superior thyroid artery. Results demonstrate that this small artery has only a marginal effect on the overall flow characteristics within the carotid sinus. However, it does have significant effects on flow patterns in the common-external side branch. An alternative approach is proposed to compensate for the absence of this small artery in numerical calculations.

Relationship between concussion and neuropsychological performance in college football players.

CONTEXT: Despite the high prevalence and potentially serious outcomes associated with concussion in athletes, there is little systematic research examining risk factors and short- and long-term outcomes. OBJECTIVES: To assess the relationship between concussion history and learning disability (LD) and the association of these variables with neuropsychological performance and to evaluate postconcussion recovery in a sample of college football players. DESIGN, SETTING, AND PARTICIPANTS: A total of 393 athletes from 4 university football programs across the United States received preseason baseline evaluations between May 1997 and February 1999. Subjects who had subsequent football-related acute concussions (n = 16) underwent neuropsychological comparison with matched control athletes from within the sample (n = 10). MAIN OUTCOME MEASURES: Clinical interview, 8 neuropsychological measures, and concussion symptom scale ratings at baseline and after concussion. RESULTS: Of the 393 players, 129 (34%) had experienced 1 previous concussion and 79 (20%) had experienced 2 or more concussions. Multivariate analysis of variance yielded significant main effects for both LD (P<.001) and concussion history (P=.009), resulting in lowered baseline neuropsychological performance. A significant interaction was found between LD and history of multiple concussions and LD on 2 neuropsychological measures (Trail-Making Test, Form B [P=.007] and Symbol Digit Modalities Test [P=.009]), indicating poorer performance for the group with LD and multiple concussions compared with other groups. A discriminant function analysis using neuropsychological testing of athletes 24 hours after acute in-season concussion compared with controls resulted in an overall 89.5% correct classification rate. CONCLUSIONS: Our study suggests that neuropsychological assessment is a useful indicator of cognitive functioning in athletes and that both history of multiple concussions and LD are associated with reduced cognitive performance. These variables may be detrimentally synergistic and should receive further study.

The numerical analysis of fluid-solid interactions for blood flow in arterial structures. Part 1: A review of models for arterial wall behaviour.

The structural response of a large artery is characteristically complex and includes the highly non-linear, history-dependent response of a nonhomogeneous anisotropic structure undergoing finite deformations. The mechanics of the arterial wall has been studied for nearly two centuries. The goals of such research range from the desire to have a basic knowledge and understanding of the mechanics and physiology of this complex structure to the need for data and methods for the design of arterial prostheses. In this paper, the models for arterial wall behaviour are critically reviewed. Firstly, the structure and general characteristics of the arterial wall are discussed. This is followed by a comprehensive review of the constitutive laws. Finally, structural analyses of the arterial wall by mathematical and numerical methods are discussed. Predictions using the authors' preferred models give focus to important issues, and in Part 2 the review and predictions are extended to the fluid solid coupled situation.

The numerical analysis of fluid-solid interactions for blood flow in arterial structures. Part 2: Development of coupled fluid-solid algorithms.

In this paper, the authors extend their study of wall mechanics given in Part 1 to the overall problem of fluid-solid interactions in arterial flows. Fluid-solid coupling has become a specific topic in computational methods and applied mechanics. In this review, firstly, the effects of elasticity of blood vessels on wave propagation and local flow patterns in large arteries are discussed. Then, numerical techniques are reviewed together with the alternative coupled methods available in fluid--wall models. Finally, a novel numerical alogorithm combining two commercial codes for coupled solid/fluid problems is presented. As a consequence of the present studies, wall effects are now able to be included in predictions of haemodynamics in a clinical context.

Magnetic resonance image processing and structured grid generation of a human abdominal bifurcation.

Magnetic resonance angiography (MRA) offers a non-invasive approach to the acquisition of anatomically accurate human arterial structure. Combining the latest computational fluid dynamics (CFD) techniques with clinical data from MRA, the detailed haemodynamics information in the human circulation system can be obtained. In this paper, a novel computer method is presented, which generates automatically a computational grid for a human abdominal bifurcation from a set of conventional MRA images. The method covers the complete sequence from MR image segmentation, 3-D model construction, grid generation, to grid quality evaluation. Results demonstrate that the computer program developed is capable of generating a good quality grid for human arterial bifurcations from MRA images with minimum user input. The resultant grid can be used directly for further computer simulation of the flow.