Measures of physical functioning after hip fracture: construct validity and responsiveness of performance-based and self-reported measures.

OBJECTIVES: this study aimed to investigate the construct validity and responsiveness of performance-based and self-reported measures of strength, mobility and balance after hip fracture. DESIGN: secondary analysis of clinical trial data. SUBJECTS: a total of 148 older people undergoing hip fracture rehabilitation. METHODS: correlation coefficients assessed construct validity. Internal responsiveness was assessed by calculating effect sizes (ES) I and II. Area under the receiver operating characteristic curve (AUC) assessed external responsiveness with change in EuroQol as the reference. RESULTS: correlations between performance-based and self-reported measures were small to medium (strength r = 0.17, mobility r = 0.45 and balance r = 0.37). The most responsive performance-based measures included walking speed (ESI 1.7, ESII 1.2), Physical Performance and Mobility Examination (ESI 1.3, ESII 1.0) and chair-rise test (ESI 1.1, ESII 0.8). Self-reported mobility (ESI 0.8, ESII 0.6) and strength (ESI 0.8, ESII 0.6) were more responsive than self-reported balance (ESI 0.3, ESII 0.2). External responsiveness (AUC) was greatest for walking speed (0.72) and lowest for the measures of body sway (0.53). CONCLUSION: self-reported and performance-based indices appear to assess different constructs and may provide complementary information about physical functioning in people after hip fracture. Measures of strength and mobility showed greater ability to detect change than measures of balance.

Human mesenchymal stem cells engraft and demonstrate site-specific differentiation after in utero transplantation in sheep.

Mesenchymal stem cells are multipotent cells that can be isolated from adult bone marrow and can be induced in vitro and in vivo to differentiate into a variety of mesenchymal tissues, including bone, cartilage, tendon, fat, bone marrow stroma, and muscle. Despite their potential clinical utility for cellular and gene therapy, the fate of mesenchymal stem cells after systemic administration is mostly unknown. To address this, we transplanted a well-characterized human mesenchymal stem cell population into fetal sheep early in gestation, before and after the expected development of immunologic competence. In this xenogeneic system, human mesenchymal stem cells engrafted and persisted in multiple tissues for as long as 13 months after transplantation. Transplanted human cells underwent site-specific differentiation into chondrocytes, adipocytes, myocytes and cardiomyocytes, bone marrow stromal cells and thymic stroma. Unexpectedly, there was long-term engraftment even when cells were transplanted after the expected development of immunocompetence. Thus, mesenchymal stem cells maintain their multipotential capacity after transplantation, and seem to have unique immunologic characteristics that allow persistence in a xenogeneic environment. Our data support the possibility of the transplantability of mesenchymal stem cells and their potential utility in tissue engineering, and cellular and gene therapy applications.

Fitness training for cardiorespiratory conditioning after traumatic brain injury.

BACKGROUND: Cardiorespiratory deconditioning is a common sequelae after traumatic brain injury (TBI). Clinically, fitness training is implemented to address this impairment, however this intervention has not been subject to rigorous review. OBJECTIVES: The primary objective was to evaluate whether fitness training improves cardiorespiratory fitness in people who have sustained a TBI. SEARCH STRATEGY: We searched ten electronic databases (Cochrane Injuries Group Trials Register; Cochrane Central Register of Controlled Trials (CENTRAL); EMBASE; PubMed (MEDLINE); CINAHL; AMED; SPORTDiscus; PsycINFO; PEDro and PsycBITE) and two clinical trials registers (TrialsCentral and Current Controlled Trials). The last search was August 2007. In addition we screened reference lists from included studies and contacted trialists to identify further studies. SELECTION CRITERIA: Randomised controlled studies with TBI participants were eligible if they compared an exercise programme incorporating cardiorespiratory fitness training to usual care, a non-exercise intervention or no intervention. DATA COLLECTION AND ANALYSIS: Two authors independently screened the search output, extracted data and assessed quality. All trialists were contacted for additional information. Mean difference and 95% confidence intervals (CI) were calculated for continuous data and risk difference or odds ratio and 95% CI were calculated for dichotomous data. Data were pooled when there were sufficient studies with clinical and statistical homogeneity. MAIN RESULTS: Six studies, incorporating 303 participants, were included. The participants were primarily males, in their mid thirties who had sustained a severe TBI. The studies were clinically diverse with regard to the interventions, time post-injury and the outcome measures used; therefore, the primary outcome could not be pooled. Three of the six studies indirectly assessed change in cardiorespiratory fitness after fitness training using the peak power output obtained during cycle ergometry (either at volitional fatigue or at a predetermined endpoint, that is, a percentage of predicted heart rate maximum). Cardiorespiratory fitness was improved after fitness training in one study (mean difference 59 watts, 95% CI 24 to 94), whilst there was no significant improvement in the other two studies. Four of the six studies had no drop-outs from their intervention group and no adverse events were reported in any study. AUTHORS' CONCLUSIONS: There is insufficient evidence to draw any definitive conclusions about the effects of fitness training on cardiorespiratory fitness. Whilst it appears to be a safe and accepted intervention for people with TBI, more adequately powered and well-designed studies are required to determine the effects across a range of outcome measures.

Treadmill training and body weight support for walking after stroke.

BACKGROUND: Treadmill training, with or without some body weight supported using a harness, is a method of treating walking after stroke. A systematic review is required to assess the cost, effectiveness, and acceptability of this treatment. OBJECTIVES: To assess the effectiveness of treadmill training and body weight support, individually or in combination, in the treatment of walking after stroke. The primary outcomes investigated were walking speed, endurance and dependency. SEARCH STRATEGY: We searched the Cochrane Stroke Group Trials Register (last searched 2 March 2005), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 4, 2004), MEDLINE (1966 to January 2005), EMBASE (1980 to February 2005), CINAHL (1982 to February 2005) and PEDro (last searched 2 March 2005). In addition, we handsearched relevant conference proceedings, screened reference lists and contacted trialists to identify further published and unpublished trials. SELECTION CRITERIA: Randomised or quasi-randomised controlled and cross-over trials of treadmill training and body weight support, individually or in combination, for the treatment of walking after stroke were eligible. DATA COLLECTION AND ANALYSIS: Two authors independently selected trials, extracted data, and assessed quality. We contacted trialists for additional information. We used a fixed-effect model for analysis, but if heterogeneity existed a random-effects model was used. We analysed the results as weighted mean differences (WMD) for continuous variables and relative risk (RR) for dichotomous variables. MAIN RESULTS: Fifteen trials (622 participants) were included. There were no statistically significant differences between treadmill training, with or without body weight support, and other interventions for walking speed or dependence. Among participants who could walk independently at the start of treatment, treadmill training with body weight support tended to produce higher walking speeds (WMD 0.09 m/s, 95% confidence interval (CI) -0.02 to 0.20 for speed; fixed-effect), but this result was not statistically significant. An individual trial tended to support the use of treadmill training with body weight support for dependent walkers as compared to treadmill training alone. One of three individual trials indicated that independent walkers may benefit from treadmill training combined with other task-orientated exercise. However, data are very limited. Adverse events occurred more frequently in participants receiving treadmill training but these were not judged to be clinically serious events. AUTHORS' CONCLUSIONS: Overall no statistically significant effect of treadmill training with or without body weight support was detected. Although individual studies suggested that treadmill training with body weight support may be more effective than treadmill training alone and that treadmill training plus task-oriented exercise may be more effective than sham exercises, further trials are required to confirm these findings.

3-Acyl-4-hydroxyquinolin-2(1H)-ones. Systemically active anticonvulsants acting by antagonism at the glycine site of the N-methyl-D-aspartate receptor complex.

Most full antagonists at the glycine site of the NMDA receptor contain a carboxylic acid, which we believe to be detrimental to penetration of the blood-brain barrier. By consideration of a pharmacophore, novel antagonists at this site have been designed in which the anionic functionality is a vinylogous acid, in the form of a 4-hydroxyquinolin-2(1H)-one. In this series, a 3-substituent is necessary for binding, and correct manipulation of this group leads to compounds such as the 3-(3-hydroxyphenyl)propargyl ester 24 (L-701,273), with an IC50 for displacement of [3H]-L-689,560 binding of 0.17 microM and Kb against NMDA in the cortical slice of 1.39 microM. Compounds were tested for their ability to prevent audiogenic seizure in DBA/2 mice; the most potent compound in this series is the cyclopropyl ketone 42 (L-701,252), with an ED50 of 4.1 mg/kg ip. A model is proposed for binding to the glycine site, in which an important interaction is of a putative receptor cation with the pi-system of the 3-substituent.

2-Carboxytetrahydroquinolines. Conformational and stereochemical requirements for antagonism of the glycine site on the NMDA receptor.

2-Carboxy-1,2,3,4-tetrahydroquinoline derivatives, derived from kynurenic acid, have been synthesized and evaluated for in vitro antagonist activity at the glycine site on the NMDA receptor. 2,3-Dihydrokynurenic acids show reduced potency relative to the parent lead compounds (Table I) possibly as a result of conformational effects. Removal of the 4-oxo group results in further reduced potency, but introduction of a cis-carboxymethyl group to the 4-position restores antagonist activity (Tables III and IV). Replacement of the keto group of 5,7-dichloro-2,3-dihydrokynurenic acid with other alternative H-bonding groups, for example cis- and trans-benzyloxycarbonyl and cis- and trans-carboxamido (Table V), gives comparable activity, but there is negligible stereoselectivity. A significant increase in potency and stereoselectivity is seen within the 4-acetate series (Table VI). The trans-4-acetic acid is significantly more potent than the corresponding lead kynurenic acid and has 100-fold greater affinity than the cis isomer. The results are consistent with a requirement in binding for a pseudoequatorially placed 2-carboxylate and clearly demonstrate the importance for binding of a correctly positioned hydrogen-bond-accepting group at the 4-position. The high-affinity binding of an anionic group in the 4-substituent binding pocket suggests that the glycine site and the neurotransmitter recognition (NMDA) site may have some features in common.

4-Amido-2-carboxytetrahydroquinolines. Structure-activity relationships for antagonism at the glycine site of the NMDA receptor.

trans-2-Carboxy-5,7-dichloro-4-amidotetrahydroquinolines, evolved from the lead 5,7-dichlorokynurenic acid, have been synthesized and tested for in vitro antagonist activity at the glycine site on the N-methyl-D-aspartate (NMDA) receptor. Optimization of the 4-substituent has provided antagonists having nanomolar affinity, including the urea trans-2-carboxy-5,7-dichloro-4[[(phenylamino)carbonyl]amino]-1,2,3, 4-tetrahydroquinoline (35; IC50 = 7.4 nM vs [3H]glycine binding; Kb = 130 nM for block of NMDA responses in the rat cortical slice), which is one of the most potent NMDA antagonists yet found. The absolute stereochemical requirements for binding were found to be 2S,4R, showing that, in common with other glycine-site NMDA receptor ligands, the unnatural configuration at the alpha-amino acid center is required. The preferred conformation of the trans-2,4-disubstituted tetrahydroquinoline system, as shown by X-ray crystallography and 1H NMR studies, places the 2-carboxyl pseudoequatorial and the 4-substituent pseudoaxial. Modifications of the 4-amide show that bulky substituents are tolerated and reveal the critical importance for activity of correct positioning of the carbonyl group. The high affinity of trans-2-carboxy-5,7-dichloro-4-[1-(3-phenyl-2-oxoimidazolidinyl)]- 1,2,3,4-tetrahydroquinoline (55; IC50 = 6 nM) suggests that the Z,Z conformer of the phenyl urea moiety in 35 is recognized by the receptor. Molecular modeling studies show that the 4-carbonyl groups of the kynurenic acids, the tetrahydroquinolines, and related antagonists based on N-(chlorophenyl)glycine, can interact with a single putative H-bond donor on the receptor. The results allow the establishment of a three-dimensional pharmacophore of the glycine receptor antagonist site, incorporating a newly defined bulk tolerance/hydrophobic region.

Treadmill training and body weight support for walking after stroke.

BACKGROUND: Treadmill training, with some body weight supported using a harness, is a method of treating walking after stroke. Systematic review is required to assess the cost, effectiveness and acceptance of this treatment. OBJECTIVES: To assess the effectiveness of treadmill training and/or body weight support in the treatment of walking after stroke. The primary outcomes investigated were walking speed and walking dependency. SEARCH STRATEGY: We searched the Cochrane Stroke Group Trials Register (last searched 21 March 2003), the Cochrane Central Register of Controlled Trials (Cochrane Library, Issue 1 2003), MEDLINE (1966-March 2003), EMBASE (1980-March 2003), CINAHL (1982-February 2003) and PEDro (last searched 21 March 2003). In addition, we handsearched relevant conference proceedings, screened reference lists and contacted trialists to identify further published and unpublished trials. SELECTION CRITERIA: Randomised, or quasi-randomised, controlled and cross-over trials of treadmill training and/or body weight support for the treatment of walking after stroke were eligible. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected trials and extracted data. Trialists were contacted for additional information. A fixed effects model was used for analysis, but if heterogeneity existed (Chi squared statistic) a random effects model was used. Results were analysed as weighted mean differences (WMD) for continuous variables and relative risk (RR) for dichotomous variables. The main outcome variables were walking speed and dependency. MAIN RESULTS: Eleven trials (458 participants) were included. There were no statistically significant differences between treadmill training, with or without body weight support, and other interventions for walking speed or dependence. There was a small trend toward the effectiveness of treadmill training with body weight support for participants who could walk independently (WMD: 0.24 m/sec, 95% CI: -0.19 to 0.66 for speed; random effects). The one trial which compared treadmill training with and without body weight support showed benefit at the end of follow-up (mean difference: 0.22 m/sec, 95% CI: 0.05 to 0.39). Adverse events occurred slightly more frequently in participants receiving treadmill training, although statistically there were no differences. REVIEWER'S CONCLUSIONS: Overall, no statistically significant effect of treadmill training and body weight support was detected. However, among people who could walk independently, treadmill training with body weight support appeared to be more effective than other interventions at improving walking speed, but this conclusion was not robust.

The effect of casting combined with stretching on passive ankle dorsiflexion in adults with traumatic head injuries.

BACKGROUND AND PURPOSE: Ankle plantar-flexion contractures are a common problem following traumatic head injury. Although serial casting is used to correct and prevent ankle plantar-flexion contractures, treatment efficacy has not been evaluated using an experimental design. The aim of this research was to establish the effect of a regimen of casting combined with stretching on passive ankle dorsiflexion motion. SUBJECTS: Nine people who had sustained traumatic closed head injuries and had limited dorsiflexion motion participated in the study. METHODS: A crossover design was used in the study. Subjects were assigned to both experimental and control groups. Torque-controlled measurements of passive ankle dorsiflexion motion were obtained for all subjects before and after 1 week of casting combined with stretching, as well as before and after a 1-week control period. The order of the experimental and control conditions was randomized. RESULTS: Passive ankle dorsiflexion increased by a mean of 13.5 degrees (SD = 9.3) during the experimental condition, as compared with a mean decrease of 1.9 degrees (SD = 10.2) during the control condition. The difference between the experimental and control conditions was statistically significant. CONCLUSION AND DISCUSSION: These findings suggest that casting combined with stretching is an effective method of correcting ankle plantar-flexion contractures in patients with traumatic head injuries.

PEDro. A database of randomized trials and systematic reviews in physiotherapy.

This paper describes PEDro, the Physiotherapy Evidence Database. PEDro is a web-based database of randomized controlled trials and systematic reviews in physiotherapy. It can be accessed free of charge at http://ptwww.cchs.usyd.edu.au/pedro. The database contains bibliographic details and abstracts of most English-language randomized trials and systematic reviews in physiotherapy, and of many trials and reviews in other languages. Trials on the database are rated on the basis of their methodological quality so that users of the database can quickly identify trials of high quality. Trials and systematic reviews are extensively indexed to facilitate searching. PEDro provides an important information resource to support evidence-based clinical practice.

Normative data for passive ankle plantarflexion--dorsiflexion flexibility.

OBJECTIVE: To describe the normal distribution parameters for measures of passive ankle plantarflexion-dorsiflexion flexibility obtained from a large sample of able-bodied young adult subjects. DESIGN: Seven variables were assessed and descriptive analyses were conducted. BACKGROUND: While assessment of plantarflexion-dorsiflexion flexibility is an important component of a clinical examination of plantarflexion contracture, there is limited normative data available that can be used as a reference for clinical decision-making. METHODS: Data were collected from 300 able-bodied male and female subjects aged between 15 and 34 years. Both ankles were measured. Load-displacement curves were collected using a manually controlled instrumented footplate. Six variables were extracted from these curves: passive torque at zero and 10 deg, passive stiffness at zero and 10 deg, and two coefficients from an equation fitted to the curve (i.e., k and b). The seventh variable, passive dorsiflexion range of motion, was quantified using a clinical procedure. RESULTS: Flexibility variables did not differ between the left and right ankles, nor between the dominant and non-dominant legs. All variables were normally distributed. These distributions can, therefore, be adequately described using their mean and standard deviation values. CONCLUSIONS: This study has substantially increased the available database on plantarflexion-dorsiflexion flexibility and forms the basis of norm-referenced clinical tests.

Time course of stress relaxation and recovery in human ankles.

OBJECTIVE: To characterise the time course of stress relaxation and recovery from stress relaxation in human ankles. DESIGN: Two experiments were conducted. The first used a randomised within-subjects design, and the second used a randomised between-subjects regression design. BACKGROUND: Several studies have described the time course of stress relaxation in human joints, but most have looked only at the effects of short durations of stretch. The time course of recovery from stretch in human ankles has not been documented. METHODS: In the first experiment, one ankle of each of eight subjects was stretched to a fixed dorsiflexion angle for 20 min. The ankle was then released for 2 min (during which time subjects either remained relaxed or performed isometric contractions), then stretched again. In a second experiment, on 24 subjects, the ankle was stretched for 20 min, then released between 0 and 20 min, then stretched again. In both experiments, subjects remain relaxed and ankle torque was measured continuously. RESULTS: When a constant-angle stretch was applied to the ankle, torque declined bi-exponentially towards an asymptote that was 58% of the initial torque. Nearly 5 min of stretch were required to obtain half of the maximal possible stress relaxation. Torque had recovered by 43% within 2 min of the release of stretch, but the degree of recovery did not appear to depend on whether subjects remained relaxed or performed isometric contractions. The time course of recovery was similar to the time course of stress relaxation. CONCLUSIONS: Long duration stretches are required to produce a large proportion of the maximal possible stress relaxation. Recovery is initially rapid when the stretch is released. RELEVANCE: These data provide a description of the time course of the effects of stretch, and of the subsequent relief of stretch, on mechanical properties of human ankles.

Inter-rater reliability and concurrent validity of step length and step width measurement after traumatic brain injury.

PURPOSE: To determine the inter-rater reliability and concurrent validity of step length and step width measurement after traumatic brain injury. METHOD: Twelve people with traumatic brain injury completed six comfortable and six fast paced walking trials over a 10 m distance. Step length and step width were measured by five observers using two procedures. First, using pens taped on the subjects' heels which marked the floor at each heel strike and a tape measure. Second, by videotaping the subjects' feet as they walked on a mat marked with 5 cm grids and using a computer program to digitize foot position and calculate step length and width. RESULTS: The inter-rater reliability of step length and width measurements was very high, with intraclass correlation coefficients between 0.94 and 1.00, for both procedures. Concurrent validity was excellent, with correlations between the procedures ranging from 0.93 to 1.00. However, attaching pens to the heels did cause a slight reduction in right step length and walking speed when walking at a fast or comfortable pace, respectively. CONCLUSIONS: Assessing step length and width using pens taped to the subjects' heels and a tape measure is a reliable and valid clinical measure after traumatic brain injury.

Nanoparticle inhalation impairs coronary microvascular reactivity via a local reactive oxygen species-dependent mechanism.

We have shown that nanoparticle inhalation impairs endothelium-dependent vasodilation in coronary arterioles. It is unknown whether local reactive oxygen species (ROS) contribute to this effect. Rats were exposed to TiO(2) nanoparticles via inhalation to produce a pulmonary deposition of 10 microg. Coronary arterioles were isolated from the left anterior descending artery distribution, and responses to acetylcholine, arachidonic acid, and U46619 were assessed. Contributions of nitric oxide synthase and prostaglandin were assessed via competitive inhibition with N(G)-Monomethyl-L-Arginine (L-NMMA) and indomethacin. Microvascular wall ROS were quantified via dihydroethidium (DHE) fluorescence. Coronary arterioles from rats exposed to nano-TiO(2) exhibited an attenuated vasodilator response to ACh, and this coincided with a 45% increase in DHE fluorescence. Coincubation with 2,2,6,6-tetramethylpiperidine-N-oxyl and catalase ameliorated impairments in ACh-induced vasodilation from nanoparticle exposed rats. Incubation with either L-NMMA or indomethacin significantly attenuated ACh-induced vasodilation in sham-control rats, but had no effect in rats exposed to nano-TiO(2). Arachidonic acid induced vasoconstriction in coronary arterioles from rats exposed to nano-TiO(2), but dilated arterioles from sham-control rats. These results suggest that nanoparticle exposure significantly impairs endothelium-dependent vasoreactivity in coronary arterioles, and this may be due in large part to increases in microvascular ROS. Furthermore, altered prostanoid formation may also contribute to this dysfunction. Such disturbances in coronary microvascular function may contribute to the cardiac events associated with exposure to particles in this size range.

Effects of rehabilitation after ankle fracture: a Cochrane systematic review.

BACKGROUND: Ankle fracture is one of the most common lower limb fractures. People experience limitations in activities after ankle fracture. OBJECTIVES: The aim of this review was to evaluate the effects of rehabilitation interventions after ankle fracture in adults. METHODS: Electronic databases, reference lists of included studies and relevant systematic reviews, and clinical trials registers were searched for randomised and quasi-randomised controlled trials with adults undergoing any interventions for rehabilitation after ankle fracture. The primary outcomes were activity limitation and adverse events. Two reviewers independently screened search results, assessed methodological quality, and extracted data. RESULTS: Thirty-one studies were included. Clinical and statistical heterogeneity, or the low number of studies in the comparison, prevented meta-analyses in most instances. After surgical fixation, commencing exercise in a removable brace or splint significantly improved activity limitation but also led to a higher rate of adverse events (relative risk 2.61, 95% CI 1.72 to 3.97). Most other rehabilitation interventions did not show an effect in improving activity limitation. CONCLUSIONS: There is limited evidence supporting the use of a removable type of immobilisation and exercise during the immobilisation period for improving activity limitation. Because of the potential increased risk, the patient's ability to comply with this treatment regimen is essential. More clinical trials that are well-designed and adequately-powered are required to strengthen current evidence.

Effects of 6 months of regular passive movements on ankle joint mobility in people with spinal cord injury: a randomized controlled trial.

STUDY DESIGN: Assessor-blinded within-subject randomized controlled trial. OBJECTIVE: To determine the effects of 6 months of regular passive movements on ankle joint mobility in people with spinal cord injury. SETTING: Community, Australia. METHODS: A total of 20 people with tetraplegia living in the community had one ankle randomized to a control group and the other to an experimental group. Carers administered passive movements to participants' experimental ankles for 10 min, 10 times a week for 6 months. The control ankles were left untreated. The primary outcome was passive ankle dorsiflexion range of motion. RESULTS: Adherence was high (mean adherence rate of 96%). Ankle dorsiflexion range of motion decreased by a mean (s.d.) of 2 degrees (4) in control ankles and increased by 2 degrees (4) in experimental ankles. The mean (95% confidence interval, CI) effect on ankle dorsiflexion range of motion was 4 degrees (95% CI, 2-6 degrees ). CONCLUSION: Regular passive movements have small effects on ankle joint mobility. It is unclear if these effects are clinically worthwhile.

Validity of the modified 20-metre shuttle test: assessment of cardiorespiratory fitness in people who have sustained a traumatic brain injury.

PRIMARY OBJECTIVE: To validate the modified 20-metre shuttle test in adults who have sustained a traumatic brain injury (TBI). DESIGN: Single-sample validity study. SETTING: Brain injury rehabilitation unit. PARTICIPANTS: Twenty-four adults with severe TBI, discharged from hospital for at least 6-months. PROTOCOL: Participants attended the facility for a familiarization session, followed by a symptom-limited treadmill test and a modified shuttle test on two separate days. The treadmill test was based on an individualised protocol which used a physiotherapist-selected speed and increments in gradient every minute until volitional fatigue. The modified shuttle test was externally-paced and commenced with a speed of 2.4 km h(-1) which increased every minute until volitional fatigue. MAIN MEASURES: Four primary measures were taken from both tests: peak oxygen uptake, peak heart rate, maximal velocity and rating of perceived exertion. RESULTS: All participants completed the study. There were no adverse events. A high correlation was observed between the modified shuttle test and the treadmill test for peak oxygen uptake, peak heart rate and maximal velocity (r = 0.96, r = 0.80, r = 0.82, respectively; p < 0.001), but not for rating of perceived exertion (r = 0.013, p = 0.952). CONCLUSION: The modified shuttle test is a valid measure of cardiorespiratory fitness in people who have sustained a TBI.