Use of an upright power wheelchair in spinal cord injury: a case series.

Objective: To explore independence, usability, and self-reported quality of life (QOL) in eligible persons with spinal cord injury (SCI) who used a standing powered wheelchair over a 12-week period. Setting: VA SCI research facility. Participants: Four participants with chronic SCI who use a wheelchair as the primary means of mobility. Intervention: A standing power wheelchair was used three times a week (3.5 h/session) for 12 weeks in a supervised setting. Main Outcome Measures: safety, usability and feasibility, blood pressure in seated and standing positions, bowel, bladder, and pain item banks from the SCI-QOL Physical-Medical-Health domain, and overall user satisfaction with the device. Results: Participants consistently maintained normal blood pressure responses between seated and standing positions throughout the training sessions and learned to perform all the mobility tasks safely and independently. Participants reported improvements on the SCI-QOL and were generally satisfied with the upright standing power wheelchair. Conclusions: In this small case series of chronic, non-ambulatory individuals with SCI, the standing powered wheelchair was shown to be safe and efficacious.

Characterization for the Similarity Assessment between Proposed Biosimilar SB12 and Eculizumab Reference Product Using a State-of-the-Art Analytical Method.

BACKGROUND: SB12 is being developed as a proposed biosimilar to eculizumab reference product (RP), a humanized monoclonal antibody (IgG2/4 kappa immunoglobulin) that binds to the human C5 complement protein. Binding to this protein inhibits complement-mediated intravascular hemolysis by blocking its cleavage into C5a and C5b. Eculizumab RP is indicated for the treatment of patients with paroxysmal nocturnal hemoglobinuria (PNH) to reduce hemolysis, atypical hemolytic uremic syndrome (aHUS) to inhibit complement-mediated thrombotic microangiopathy, generalized myasthenia gravis who are anti-acetylcholine receptor antibody-positive, and neuromyelitis optica spectrum disorder in adult patients who are anti-aquaporin-4 antibody-positive. OBJECTIVE: The objective of this study was to demonstrate structural, physicochemical, and biological similarity between eculizumab RP and SB12 using various state-of-the-art analytical methods. METHODS: Comprehensive analytical characterization was conducted with side-by-side comparison of SB12 with European Union (EU) and United States (US) eculizumab RPs using various analytical methods (more than 40 state-of-the-art assays). Comparisons included purity, product-related impurity, charge heterogeneity, primary structure, post-translational modification, higher-order structure, quantity, Fab-related biological activities (potency and binding activity), and Fc-related biological activities. RESULTS: Based on the analytical similarity assessment, the structural, physicochemical, and biological characterization results demonstrated that SB12 is highly similar to the EU and US eculizumab RP. In the structural aspects, it was confirmed that there is no difference between post-translational modification profiles and higher-order structures of SB12 compared with the eculizumab RP. Product-related impurities in the form of aggregates and charge variants were also confirmed to be similar. Mechanism of action (MoA)-related biological activities showed that SB12 is highly similar to the EU and US eculizumab RP with respect to overall critical and non-critical quality attributes analyzed. Moreover, similarity of comparative binding tendency of SB12 and eculizumab RP to Fc gamma receptors and C1q was confirmed through additional characterization methods. Based on these results, SB12 is expected to have highly similar safety and efficacy compared with eculizumab RP. CONCLUSION: In summary, the overall analytical characterization and similarity assessment results show that SB12 is highly similar to the EU and US eculizumab RP in terms of structural, physicochemical, biophysical, and biological attributes.

Predicting physical activity intensity using raw accelerometer signals in manual wheelchair users with spinal cord injury.

STUDY DESIGN: Cross-sectional validation study. OBJECTIVES: The performance of previously published physical activity (PA) intensity cutoff thresholds based on proprietary ActiGraph counts for manual wheelchair users (MWUs) with spinal cord injury (SCI) was initially evaluated using an out-of-sample dataset of 60 individuals with SCI. Two types of PA intensity classification models based on raw accelerometer signals were developed and evaluated. SETTING: Research institutions in Pittsburgh PA, Birmingham AL, and Bronx NY. METHODS: Data were collected from 60 MWUs with SCI who followed a structured activity protocol while wearing an ActiGraph activity monitor on their dominant wrist and portable metabolic cart which measured criterion PA intensity. Data was used to assess published models as well as develop and assess custom models using recall, specificity, precision, as well as normalized Mathew's correlation coefficient (nMCC). RESULTS: All the models performed well for predicting sedentary vs non-sedentary activity, yielding an nMCC of 0.87-0.90. However, all models demonstrated inadequate performance for predicting moderate to vigorous PA (MVPA) with an nMCC of 0.76-0.82. CONCLUSIONS: The mean absolute deviation (MAD) cutoff threshold yielded the best performance for predicting sedentary vs non-sedentary PA and may be used for tracking daily sedentary activity. None of the models displayed strong performance for MVPA vs non-MVPA. Future studies should investigate combining physiological measures with accelerometry to yield better prediction accuracies for MVPA.

The Effect of Exoskeletal-Assisted Walking on Spinal Cord Injury Bowel Function: Results from a Randomized Trial and Comparison to Other Physical Interventions.

Bowel function after spinal cord injury (SCI) is compromised because of a lack of voluntary control and reduction in bowel motility, often leading to incontinence and constipation not easily managed. Physical activity and upright posture may play a role in dealing with these issues. We performed a three-center, randomized, controlled, crossover clinical trial of exoskeletal-assisted walking (EAW) compared to usual activity (UA) in people with chronic SCI. As a secondary outcome measure, the effect of this intervention on bowel function was assessed using a 10-question bowel function survey, the Bristol Stool Form Scale (BSS) and the Spinal Cord Injury Quality of Life (SCI-QOL) Bowel Management Difficulties instrument. Fifty participants completed the study, with bowel data available for 49. The amount of time needed for the bowel program on average was reduced in 24% of the participants after EAW. A trend toward normalization of stool form was noted. There were no significant effects on patient-reported outcomes for bowel function for the SCI-QOL components, although the time since injury may have played a role. Subset analysis suggested that EAW produces a greater positive effect in men than women and may be more effective in motor-complete individuals with respect to stool consistency. EAW, along with other physical interventions previously investigated, may be able to play a previously underappreciated role in assisting with SCI-related bowel dysfunction.

Exoskeletal-assisted walking may improve seated balance in persons with chronic spinal cord injury: a pilot study.

STUDY DESIGN: Pre-post intervention. OBJECTIVE: To explore the potential effect of exoskeletal-assisted walking (EAW) on seated balance for persons with chronic motor complete spinal cord injury (SCI). SETTING: A SCI research center. METHODS: Eight participants who were over 18 years of age with chronic SCI and used a wheelchair for mobility were enrolled. Seven able-bodied participants were used for normal seated balance comparative values. Participants with chronic SCI received supervised EAW training using a powered exoskeleton (ReWalkTM) for a median 30 sessions (range from 7 to 90 sessions). Before and after EAW training, seated balance testing outcomes were collected using computerized dynamic posturography, providing measurements of endpoint excursion (EPE), maximal excursion (MXE), and directional control (DCL). Modified functional reach test (MFRT) and the sub-scales of physical functioning and role limitations due to physical health from the Short Form (36) Health Survey (SF-36) were used to identify changes in functional activities. RESULTS: After EAW training, seated balance significantly improved in total-direction EPE and MXE (P < 0.01 and P < 0.017 respectively). The results of MFRT and sub-scales of physical functioning and role limitations due to physical health improved after EAW training but were not statistically significant. CONCLUSIONS: EAW training may have the potential to improve seated balance for persons with chronic motor complete SCI. Due to the limitations of the study, such as small sample size and lack of a control group, further studies are needed to clarify the effect of improving seated balance through EAW training.

Estimation of Physical Activity Intensity in Spinal Cord Injury Using a Wrist-Worn ActiGraph Monitor.

OBJECTIVES: To derive accelerometer count thresholds for classifying time spent in sedentary, light intensity, and moderate-to-vigorous physical activity (MVPA) in manual wheelchair users (MWUs) with spinal cord injury (SCI). DESIGN: Participants completed 18 activities of daily living and exercises for 10 minutes each with a 3-minute break between activities while wearing a COSMED K4b2 portable metabolic cart and an ActiGraph activity monitor on the dominant wrist. A linear regression was computed between the wrist acceleration vector magnitude and SCI metabolic equivalent of task (MET) for 80% of the participants to obtain thresholds for classifying different activity intensities, and the obtained thresholds were tested for accuracy on the remaining 20% of participants. This cross-validation process was iterated for 1000 times to evaluate the stability of the thresholds on data corresponding to different proportions of sedentary, light intensity, and MVPA. MET values of 1.5 or lower were classified as sedentary behavior, MET values between 1.5 and 3 were classified as light intensity, and MET values of 3 or higher were classified as MVPA. The final thresholds were then validated on an out-of-sample independent dataset. PARTICIPANTS: MWUs (N=17) with SCI in the out-of-sample validation data set. INTERVENTIONS: Not applicable. SETTING: Research lab, community MAIN OUTCOME MEASURES: Accelerometer thresholds to classify sedentary, light intensity, and MVPA were obtained and their accuracy tested using cross-validation and an out-of-sample dataset. RESULTS: The threshold between sedentary and light intensity was 2057 counts-per-minute, and the threshold between light intensity and MVPA was 11,551 counts per minute. Based on the out-of-sample validation, the obtained thresholds had an overall accuracy of 85.6%, with a sensitivity and specificity of 95.3% and 97.4% for sedentary behavior, 87.8% and 84.5% for light intensity, 68.5% and 96.3% for MVPA, respectively. CONCLUSION: Accelerometer-based thresholds can be used to accurately identify sedentary behavior. However, thresholds may not provide accurate estimations of MVPA throughout the day when participants engage in more resistance-based activities.

Mobility Skills With Exoskeletal-Assisted Walking in Persons With SCI: Results From a Three Center Randomized Clinical Trial.

Background: Clinical exoskeletal-assisted walking (EAW) programs for individuals with spinal cord injury (SCI) have been established, but many unknown variables remain. These include addressing staffing needs, determining the number of sessions needed to achieve a successful walking velocity milestone for ambulation, distinguishing potential achievement goals according to level of injury, and deciding the number of sessions participants need to perform in order to meet the Food and Drug Administration (FDA) criteria for personal use prescription in the home and community. The primary aim of this study was to determine the number of sessions necessary to achieve adequate EAW skills and velocity milestones, and the percentage of participants able to achieve these skills by 12 sessions and to determine the skill progression over the course of 36 sessions. Methods: A randomized clinical trial (RCT) was conducted across three sites, in persons with chronic (≥6 months) non-ambulatory SCI. Eligible participants were randomized (within site) to either the EAW arm first (Group 1), three times per week for 36 sessions, striving to be completed in 12 weeks or the usual activity arm (UA) first (Group 2), followed by a crossover to the other arm for both groups. The 10-meter walk test seconds (s) (10MWT), 6-min walk test meters (m) (6MWT), and the Timed-Up-and-Go (s) (TUG) were performed at 12, 24, and 36 sessions. To test walking performance in the exoskeletal devices, nominal velocities and distance milestones were chosen prior to study initiation, and were used for the 10MWT (≤ 40s), 6MWT (≥80m), and TUG (≤ 90s). All walking tests were performed with the exoskeletons. Results: A total of 50 participants completed 36 sessions of EAW training. At 12 sessions, 31 (62%), 35 (70%), and 36 (72%) participants achieved the 10MWT, 6MWT, and TUG milestones, respectively. By 36 sessions, 40 (80%), 41 (82%), and 42 (84%) achieved the 10MWT, 6MWT, and TUG criteria, respectively. Conclusions: It is feasible to train chronic non-ambulatory individuals with SCI in performance of EAW sufficiently to achieve reasonable mobility skill outcome milestones.

Identifying characteristic back shapes from anatomical scans of wheelchair users to improve seating design.

Spinal deformities are common in people who require the use of a wheelchair for mobility as a result of spinal cord injuries and other disabilities. Sitting positions vary between individuals with disabilities who use wheelchairs and individuals without disabilities. In individuals with spinal cord injury, spinal deformities can result in the development of back contours that deviate from the shape of standard rigid back support shells. The purpose of this study was to distinguish and classify various back contours of wheelchair users by utilizing digital anatomic scanning technology in order to inform the future development of back supports that would enhance postural support for those with spinal deformities. The three dimensional (3D) locations of bony landmarks were digitized when participants were in position, using a mechanical wand linked to the FastScan(tm) system commonly used to measure surface contours. Raw FastScan(tm) data were transformed according to bony landmarks. A total of 129 individuals participated in this study. A wide range of back contours were identified and categorized. Although participant characteristics (e.g., gender, diagnosis) were similar amongst the contour groups; no one characteristic explained the contours. Participants who were seated in a forward lean position had a higher amount of pelvic obliquity compared to those seated in an upright position; however, participants' back contour was not correlated with pelvic obliquity. In conclusion, an array of different back shapes were classified in our cohort through 3D laser scanning technology. The methods and technology applied in this study could be replicated in future studies to categorize ranges of back shapes in larger populations of people with spinal cord injuries. Preliminary evidence indicates that customized postural support may be warranted to optimize positioning and posture when a standard rigid shell does not align with contours of a person's back. To optimize positioning, a range of contoured rigid backrests as well as height and angle adjustability are likely needed.

Design, testing and evaluation of angle-adjustable backrest hardware.

PURPOSE: The purpose of this study was to design and evaluate a final design prototype of angle-adjustable backrest hardware. METHODS: A traditional iterative design development protocol was undertaken and completed. Before evaluation by a focus group, testing of the prototype was performed in strict accordance with ISO standards. Focus group participants were between 18 and 80 years of age, used a manual wheelchair as their primary means of mobility, and transferred independently. Individuals with pressure sores or who required of the use of specialized or custom seating for trunk support were excluded from the study. A questionnaire was administered to elicit participants' opinions on the adjustability, function and appearance of the angle-adjustable backrest device. RESULTS: The prototype successfully met the ISO testing standards. Wheelchair users (n = 8) who evaluated the device in a focus group had an overall positive response. Things they most liked about the prototype were comfort, support (function/activities) and adjustability, while things they most disliked about the prototype were problems with string and reaching back position to adjust. CONCLUSIONS: The prototype had a positive impression from participants, however, improvements on the operation method and usability were suggested. Implications for Rehabilitation The adjustable backrest is in need of development to provide function, comfort and support for manual wheelchair users. Manual wheelchair users will benefit by using the angle adjustment as they maintain their active lifestyles. Balance control while performing pressure relief in a wheelchair would be increased.

Comfort and stability of wheelchair backrests according to the TAWC (tool for assessing wheelchair discomfort).

PURPOSE: The goal of this study was thus to determine if people with different types of wheelchair backrests on their personal wheelchairs reported different levels of comfort as measured by the Tool for Assessing Wheelchair disComfort (TAWC). METHODS: Participants were between 18 and 80 years of age and were manual wheelchair users. The TAWC was used to assess the participants' wheelchair seating discomfort levels with the wheelchair and seating systems. RESULTS: We surveyed 131 wheelchair users to assess the comfort of their backrests on their personal wheelchairs and found a trend suggesting that rigid backrests are were less comfortable as compared with sling backrests. This finding was statistically significant in a subgroup of participants with tetraplegia. CONCLUSIONS: Although many clinicians expect rigid backrests to be more comfortable because they may provide more support, the higher discomfort ratings among rigid backrest users with tetraplegia may be due to sub-optimal shape, fit, adjustment or user preferences. Implications for Rehabilitation Development of a measure for long-term seating discomfort is needed. Design and development of better rigid backrests that are functional but provide adequate comfort are in need.

Health-related quality of life of community-dwelling stroke survivors: a comparison of fallers and non-fallers.

[Purpose] The purpose of this study was to compare the health-related quality of life (HRQOL) of stroke survivors between fallers and non-fallers. [Subjects] The subjects were community-dwelling stroke patients (n = 4,560) in South Korea. All stroke patients were diagnosed by a doctor. [Methods] This study used raw data from the 2014 Korean Community Health Survey. The survey was conducted from August 16, 2014, to October 31, 2014. Trained surveyors visited households selected from the sample and conducted face-to-face interviews. The content of the survey included demographic data and HRQOL. [Results] Fallers were 1,425 (31.25%), non-fallers 3,125 (68.53%), and 10 (0.22%) answered unknown. Gender, living status, occupation, and smoking experience differed significantly between the fallers and non-fallers. The domains of HRQOL, excluding VAS, also differed significantly between the fallers and non-fallers. [Conclusion] These results provide important base data for rehabilitation services for fallers among stroke survivors.

Health-related quality of life and health condition of community-dwelling populations with cancer, stroke, and cardiovascular disease.

[Purpose] The purpose of this study was to investigate health conditions and HRQoL (health-related quality of life) of community-dwelling populations with cancer, stroke, and CVD (cardiovascular disease) based on standardized data. [Subjects] The study subjects numbered 422 in total: 179 patients had cancer, 128 were stroke patients, and 115 were CVD patients. [Methods] This study used data collected during health interviews carried out as part of the sixth Korean National Health and Nutrition Examination Survey. Face-to-face health interviews were conducted by trained surveyors who visited households during 2013. The contents of the interviews included data on demographic factors, physical condition, psychological condition, and HRQoL. [Results] Stress perceptions related to health condition differed significantly across the populations of cancer, stroke, and CVD patients. The HRQoL items of mobility, self-care, usual activities, and anxiety/depression also differed significantly across these populations. [Conclusion] Healthcare teams will now be in a position to plan programs for improvement in these areas according to the features of each disease.

Comparison of quality of life according to community walking in stroke patients.

[Purpose] The aim of this study was to examine the quality of life of stroke patients according to their degree of community walking. [Subjects] This study utilized raw data from the sixth Korea National Health and Nutrition Examination Survey conducted in 2013 by the Korea Centers for Disease Control and Prevention. The subjects were noninstitutionalized stroke patients (n = 71) diagnosed by a doctor. [Methods] Trained surveyors visited households selected for the sample and conducted face-to-face interviews in conjunction with a structured questionnaire. The content of the interview included demographic data and the EuroQoL; EQ-5D-3L. Inferential statistical analysis took into account the clustering and stratification of the sample survey data as usually done in a complex survey design. A χ(2) test was performed to identify the quality of life distribution according to walking days during a typical week. Finally, logistic regression analysis was performed to identify the correlation between quality of life and walking days. [Results] Mobility, usual activities, and anxiety/depression differed significantly according to number of walking days during a normal week. No significant difference was found in the relationship between quality of life and days of walking during a normal week. [Conclusion] This study indicates that community walking every day is better than walking 1-3 days a week or no walking in terms of the effect on quality of life. However, the extent to which community walking is good for improving quality of life is unclear. Further studies need to determine the optimal duration (days) of community walking.

Interleukin-1α promotes extracellular shedding of syndecan-2 via induction of matrix metalloproteinase-7 expression.

The cell surface heparan sulfate proteoglycan, syndecan-2, is known to play an important role in the tumorigenic activity of colon cancer cells. In addition, the extracellular domain of syndecan-2 is cleaved by matrix metalloproteinase-7 (MMP-7) in various colon cancer cells, but factors involved in regulating this process remain unknown. Here, we demonstrate a role for interleukin-1α (IL-1α) in syndecan-2 shedding in colon cancer cells. Treatment of low metastatic (HT-29) and highly metastatic (HCT-116) colon cancer cells with various soluble growth factors and cytokines revealed that IL-1α specifically increased extracellular shedding of syndecan-2 in a concentration- and time-dependent manner. IL-1α did not affect the expression of syndecan-2, but did significantly reduce its cell surface levels. Notably, IL-1α increased the mRNA expression and subsequent secreted levels of MMP-7 protein and enhanced the phosphorylation of p38 and ERK mitogen-activated protein kinases. Furthermore, increased syndecan-2 shedding was dependent on the mitogen-activated protein kinase-mediated MMP-7 expression. Taken together, these data suggest that IL-1α regulates extracellular domain shedding of syndecan-2 through regulation of the MAP kinase-mediated MMP-7 expression in colon cancer cells.

Evaluation of aluminum ultralight rigid wheelchairs versus other ultralight wheelchairs using ANSI/RESNA standards.

Previous studies found that select titanium ultralight rigid wheelchairs (TURWs) had fewer equivalent cycles and less value than select aluminum ultralight folding wheelchairs (AUFWs). The causes of premature failure of TURWs were not clear because the TURWs had different frame material and design than the AUFWs. We tested 12 aluminum ultralight rigid wheelchairs (AURWs) with similar frame designs and dimensions as the TURWs using the American National Standards Institute/Rehabilitation Engineering and Assistive Technology Society of North America and International Organization for Standardization wheelchair standards and hypothesized that the AURWs would be more durable than the TURWs. Across wheelchair models, no significant differences were found in the test results between the AURWs and TURWs, except in their overall length. Tire pressure, tube-wall thickness, and tube manufacturing were proposed to be the factors affecting wheelchair durability through comparison of the failure modes, frames, and components. The frame material did not directly affect the performance of AURWs and TURWs, but proper wheelchair manufacture and design based on mechanical properties are important.

Voltage-dependent ion channel currents in putative neuroendocrine cells dissociated from the ventral prostate of rat.

Prostate neuroendocrine (NE) cells play important roles in the growth and differentiation of the prostate. Following enzymatic digestion of rat ventral prostate, the whole-cell patch-clamp technique was applied to dark, round cells that exhibited chromogranin-A immunoreactivity, a representative marker of NE cells. Under zero current-clamp conditions, putative NE cells showed hyperpolarized resting membrane potentials of some -70 mV, and spontaneous action potentials were induced by an increase in external [K+] or by the injection of current. Using a CsCl pipette solution, step-like depolarization activated high-voltage-activated Ca2+ current (HVA I(Ca)) and tetrodotoxin-resistant voltage-activated Na+ current. The HVA I(Ca) was blocked by nifedipine and omega-conotoxin GVIA, L-type and N-type Ca2+ channel blockers, respectively. Using a KCl pipette solution, the transient outward K+ current (I(to)), Ca2+ -activated K+ currents (I(K,Ca)), the non-inactivating outward current and an inwardly rectifying K+ current (I(Kir)) were identified. I(K,Ca) was suppressed by charybdotoxin (50 nM), iberiotoxin (10 nM) or clotrimazol (1 microM), but not by apamine (100 nM). I(to) was inhibited by 4-aminopyridine (5 mM). I(Kir) was identified as a Ba2+ -sensitive inwardly rectifying current in the presence of a high-K+ bath solution. The voltage- and Ca2+ -activated ion channels could play significant roles in the regulation of neurohormonal secretion in the prostate.