Efficacy of third-party chimeric antigen receptor modified peripheral blood natural killer cells for adoptive cell therapy of B-cell precursor acute lymphoblastic leukemia.

We developed an innovative and efficient, feeder-free culture method to genetically modify and expand peripheral blood-derived NK cells with high proliferative capacity, while preserving the responsiveness of their native activating receptors. Activated peripheral blood NK cells were efficiently transduced by a retroviral vector, carrying a second-generation CAR targeting CD19. CAR expression was demonstrated across the different NK-cell subsets. CAR.CD19-NK cells display higher antileukemic activity toward CD19+ cell lines and primary blasts obtained from patients with B-cell precursor ALL compared with unmodified NK cells. In vivo animal model data showed that the antileukemia activity of CAR.CD19-NK cell is superimposable to that of CAR-T cells, with a lower xenograft toxicity profile. These data support the feasibility of generating feeder-free expanded, genetically modified peripheral blood NK cells for effective "off-the-shelf" immuno-gene-therapy, while their innate alloreactivity can be safely harnessed to potentiate allogeneic cell therapy.

Learning chronobiology by improving Wikipedia.

Although chronobiology is of growing interest to scientists, physicians, and the general public, access to recent discoveries and historical perspectives is limited. Wikipedia is an online, user-written encyclopedia that could enhance public access to current understanding in chronobiology. However, Wikipedia is lacking important information and is not universally trusted. Here, 46 students in a university course edited Wikipedia to enhance public access to important discoveries in chronobiology. Students worked for an average of 9 h each to evaluate the primary literature and available Wikipedia information, nominated sites for editing, and, after voting, edited the 15 Wikipedia pages they determined to be highest priorities. This assignment (http://www.nslc.wustl.edu/courses/Bio4030/wikipedia_project.html) was easy to implement, required relatively short time commitments from the professor and students, and had measurable impacts on Wikipedia and the students. Students created 3 new Wikipedia sites, edited 12 additional sites, and cited 347 peer-reviewed articles. The targeted sites all became top hits in online search engines. Because their writing was and will be read by a worldwide audience, students found the experience rewarding. Students reported significantly increased comfort with reading, critiquing, and summarizing primary literature and benefited from seeing their work edited by other scientists and editors of Wikipedia. We conclude that, in a short project, students can assist in making chronobiology widely accessible and learn from the editorial process.

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.

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.

Technical note: A rapid enzyme-linked immunosorbent assay blood test for pregnancy in dairy and beef cattle.

The ruminant trophoblast produces pregnancy-associated glycoproteins (PAG) that can be detected in the blood of pregnant animals. The objective was to determine the accuracy of a rapid ELISA PAG-based test for the purpose of pregnancy detection in cattle. Blood was sampled from dairy cattle (539 Holstein cows, 173 Holstein heifers, 73 Guernsey cows, 22 Guernsey heifers, and 12 Jersey heifers) and crossbred beef cattle (145 cows and 46 heifers) that were >or=25 d after insemination (range = 25 to 45 d for dairy and 29 to 56 d for beef). Cattle were examined by ultrasonography for detection of pregnancy within 2 d of blood collection. Whole blood or plasma was incubated in a polystyrene tube coated with a monoclonal PAG antibody for 15 min. The tubes were then washed and subjected to sequential incubations with a biotinylated polyclonal PAG antibody (15 min, followed by wash), a horseradish peroxidase-streptavidin solution (15 min, followed by wash), and a peroxidase substrate. Tubes were visually assessed for color after 15 min (clear solution = PAG negative, not pregnant; blue solution = PAG positive, pregnant). Total assay time was approximately 90 min. The ultrasound examination was used as the standard for pregnancy diagnosis. The sensitivity (99.8 +/- 0.2%), specificity (91.7 +/- 1.4%), and negative predictive value (99.7 +/- 0.3%) for the PAG test used in dairy cattle were similar for different breeds and for cows and heifers. The positive predictive value for the test was greater in dairy heifers than in dairy cows (96.5 +/- 1.4% vs. 90.5 +/- 1.7%, respectively). In beef cattle, the sensitivity (100%), specificity (92.3 +/- 3.0%), positive predictive value (95.0 +/- 2.0%), and negative predictive value (100%) for the PAG test were similar for cows and heifers. The accuracy of the test was not different for dairy and beef cattle. In conclusion, the rapid ELISA pregnancy test based on PAG was highly sensitive and specific for pregnancy detection in dairy and beef cattle.

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.

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.

Reliability of bioimpedance spectroscopy and tonometry after breast conserving cancer treatment.

BACKGROUND: Measuring the female breast, especially after breast cancer treatment, is problematic due to breast size, texture, and patient positioning. However, being able to accurately measure changes in the breast is important, as it may help in the earlier diagnosis and treatment of early breast edema and later lymphedema. METHODS: 14 women who had undergone breast conserving surgery for breast cancer (> 12 months ago) were recruited to assess the between subject reproducibility of tonometry and bioimpedance spectroscopy (BIS). With the participant supine, two repeat measurements of the resistance of the tissues to compression (tonometry) and fluid levels (BIS) of the treated and normal breast were taken for each of the four quadrants of the breast. RESULTS: The between subject reproducibility for both measurement techniques was high, with covariance ranging from 1.29% to 3.25% for tonometry and 0.20-0.86% for BIS. CONCLUSIONS: The reliability of these two measurement techniques provides an opportunity for researchers and clinicians to easily quantify breast tissue and fluid changes which in turn may lead to the earlier diagnosis and targeted treatment of breast edema and lymphedema.

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.

Endermologie (with and without compression bandaging)--a new treatment option for secondary arm lymphedema.

Two treatment protocols are presented using the LPG Endermologie system in combination with compression bandaging as a new treatment option for secondary arm lymphedema. Both protocols were applied 4 days a week for 4 weeks but differed in Trial II in time spent clearing the regions of the trunk adjacent to the swollen limb and the addition of a larger treatment head so that a greater area could be covered more quickly. The first protocol involved 24 women and the second involved 10 women. At the end of the treatment period, both protocols demonstrated overall reductions in limb volume (134mls; 18.3% p = 0.000 and 185mls; 28%, p = 0.002), limb fluid (182mls; 28%, p = 0.000 and 216mls; 33%. p = 0.014), truncal fluid (342mls; p = 0.002 and 290mls; p = 0.066), improvements in fibrotic induration in some lymphatic territories, and significant improvements in subject reporting of heaviness, tightness, tissue hardness and limb size. Trial II demonstrated additional benefits in terms of reduction in whole arm volume at 24 hours, improved fluid and arm volume reductions, and a significant improvement in subject reported arm range of movement. The additional time spent clearing the regions adjacent to the swollen limb in the second protocol appears to produce an increase in limb volume and limb fluid loss compared to the original treatment protocol.

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.

A systematic review of common conservative therapies for arm lymphoedema secondary to breast cancer treatment.

Secondary arm lymphoedema is a chronic and distressing condition which affects a significant number of women who undergo breast cancer treatment. A number of health professional and patient instigated conservative therapies have been developed to help with this condition, but their comparative benefits are not clearly known. This systematic review undertook a broad investigation of commonly instigated conservative therapies for secondary arm lymphoedema including; complex physical therapy, manual lymphatic drainage, pneumatic pumps, oral pharmaceuticals, low level laser therapy, compression bandaging and garments, limb exercises and limb elevation. It was found that the more intensive and health professional based therapies, such as complex physical therapy, manual lymphatic drainage, pneumatic pump and laser therapy generally yielded the greater volume reductions, whilst self instigated therapies such as compression garment wear, exercises and limb elevation yielded smaller reductions. All conservative therapies produced improvements in subjective arm symptoms and quality of life issues, where these were measured. Despite the identified benefits, there is still the need for large scale, high level clinical trials in this area.

The effect of gentle arm exercise and deep breathing on secondary arm lymphedema.

The aim of this study was to explore the benefits of gentle arm exercise combined with deep breathing for secondary arm lymphedema. 38 women participated in 10 minutes of standardized arm exercise and deep breathing and were measured every 10 minutes for 1 hour, then 24 hours and 1 week post regime. A smaller cohort of 24 women continued the 10 minute exercise regime morning and evening for 1 month, with measurements being repeated at the end of this time. Directly after performing the regime, there was a reduction in arm volume of 52 mls (5.8%), with the reduction being sustained at 30 minutes (50 mls, 5.3%). Even though participants were told not to further do the exercise, at 24 hours the volume reduction was 46 mls (4.3%) and at 1 week, 33 mls (3.5%). At the one month follow-up, the reduction was 101 mls (9.0%). All reductions were statistically significant. Reported arm heaviness and tightness also statistically significantly decreased directly after the regime with the reduction in tightness being sustained at 24 hours. The reduction in heaviness was sustained at 24 hours, 1 week, and even one month after the program. Perceived limb size was significantly reduced at 1 week and at the 1 month follow-up. There was also a significant improvement in the anterior thorax tonometry reading at the 1 month follow-up.

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.

Test-re-test reliability of walking speed, step length and step width measurement after traumatic brain injury: a pilot study.

PRIMARY OBJECTIVE: Assess the test-re-test reliability of walking speed, step length and step width measurement in people with traumatic brain injury (TBI). RESEARCH DESIGN: Repeated measures (two test occasions). METHODS: Thirteen people with TBI completed four comfortable and four fast-paced walking trials of the 10 m walk test and two trials of the 6-minute walk test (6MWT). Walking speed, step length and step width were measured during the 10 m walk test and walking distance and average speed were measured during the 6MWT. The tests were repeated 1-week later. MAIN RESULTS: Walking speed and distance showed excellent test-re-test reliability, with an intra-class correlation coefficient (ICC) of 0.95-0.96. Reliability was also high for step length and width measurement (ICC 0.91-0.98). CONCLUSIONS: This test-re-test reliability means that walking speed and distance and step length and width can be used by physiotherapists to monitor improvements in walking after TBI.

The Sun Ancon Chi Machine Aerobic Exerciser: a new patient focused, home based therapy for people with chronic secondary leg lymphedema.

A significant proportion of those who survive lower torso cancer treatments will go on to develop clinically discernible bilateral or unilateral leg lymphedema. Although beneficial treatments exist for this condition, many are expensive and involve visits to outpatient clinics or allied health professionals--making the patient dependent upon others for treatment and maintenance. This clinical trial tested the efficacy of the Sun Ancon Chi Machine Aerobic Exerciser, a home based therapy that delivered both elevation and passive exercise to the legs. This machine was used in the participant's home according to a set regime with measurements being taken immediately before trial commencement, at weekly intervals and then 1 month after treatment cessation. After a three week treatment period there were statistically significant reductions in total leg volume and fluids, whole body extracellular fluid, weight and subjective leg symptoms. Lymphscintigraphy in a sub-group of patients suggested an increase in lymphatic transport in some individuals. Although some of the fluid and symptoms had returned at the 1 month follow up, none of the parameters had returned to pre-treatment levels. This finding indicates that this equipment may have ongoing beneficial effects. This clinical trial demonstrates that the Sun Ancon Chi Machine Aerobic Exerciser is an effective adjunct therapy that can be used in the patient's own home.

Deletion of the Na/K-ATPase alpha1-subunit gene (Atp1a1) does not prevent cavitation of the preimplantation mouse embryo.

Increases in Na/K-ATPase activity occur concurrently with the onset of cavitation and are associated with increases in Na(+)-pump subunit mRNA and protein expression. We have hypothesized that the alpha1-isozyme of the Na/K-ATPase is required to mediate blastocyst formation. We have tested this hypothesis by characterizing preimplantation development in mice with a targeted disruption of the Na/K-ATPase alpha1-subunit (Atp1a1) using embryos acquired from matings between Atp1a1 heterozygous mice. Mouse embryos homozygous for a null mutation in the Na/K-ATPase alpha1-subunit gene are able to undergo compaction and cavitation. These findings demonstrate that trophectoderm transport mechanisms are maintained in the absence of the predominant isozyme of the Na(+)-pump that has previously been localized to the basolateral membranes of mammalian trophectoderm cells. The presence of multiple isoforms of Na/K-ATPase alpha- and beta-subunits at the time of cavitation suggests that there may be a degree of genetic redundancy amongst isoforms of the catalytic alpha-subunit that allows blastocyst formation to progress in the absence of the alpha1-subunit.

Inter-rater reliability and concurrent validity of walking speed measurement after traumatic brain injury.

OBJECTIVE: To assess the inter-rater reliability and concurrent validity of walking speed measurement after traumatic brain injury. DESIGN: Twelve subjects each completed five comfortably paced and five fast-paced walking trials. Walking speed was measured simultaneously by five observers using a stopwatch (clinical procedure) and by infrared timing gates (gold standard). SETTING: Brain injury rehabilitation unit. SUBJECTS: People with traumatic brain injury who could walk independently and were participating in a rehabilitation programme. MAIN OUTCOME MEASURES: Walking speed over a 10-metre distance. RESULTS: The inter-rater reliability of walking speed measured using a stopwatch was very high, with an intraclass correlation coefficient of at least 0.998 for both comfortable and fast-paced tests. Concurrent validity was excellent for comfortable and fast tests, with perfect correlations between the stopwatch and infrared timing gate measurement procedures. CONCLUSIONS: Physiotherapists can use a stopwatch as a reliable and valid measurement tool to quantify walking speed over a short distance at both comfortable and fast paces in people who have sustained traumatic brain injuries.

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.

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.