Effectiveness of Group Wheelchair Maintenance Training for People with Spinal Cord Injury: A Randomized Controlled Trial.

OBJECTIVE: To assess the effectiveness of group wheelchair maintenance training and investigate participant characteristics associated with responsiveness to training. DESIGN: Randomized controlled trial with an immediate group and a waitlist control group (WLCG) who received the intervention after a 6-month delay. SETTING: Four Spinal Cord Injury Model Systems Centers. PARTICIPANTS: Manual (MWC; n=80) and power wheelchair (PWC; n=67) users with spinal cord injury (N=147). INTERVENTIONS: Two 90-minute structured wheelchair maintenance training program classes with 12-20 people per class and separate classes for MWC and PWC users. Each class included in-person hands-on demonstrations and practice of wheelchair maintenance. MAIN OUTCOME MEASURES: Separate analysis was completed for MWC and PWC users using the Wheelchair Maintenance Training Questionnaire (WMT-Q) capacity (ability to complete), performance (frequency of completion) and knowledge at baseline, 1 month, 6 months, 6 months pretraining (WLCG only), and 1 year (immediate only). RESULTS: After the intervention, participants in both the immediate and WLCG improved in maintenance capacity (MWC and PWC, P<.001) and performance (MWC and PWC, P<.001) with training. Only PWC users improved knowledge of wheelchair maintenance (P<.001). For both WLCGs (MWC and PWC), there was no difference between the 6-month pretraining time point and baseline. MWC users who responded to training had lower WMT-Q scores for all domains, whereas this was only the case for knowledge for PWC users. CONCLUSIONS: Group wheelchair skills training is effective at improving capacity to complete maintenance and performance of maintenance activities for MWC and PWC users, even in a cohort of experienced wheelchair users. For MWC users, improvements were tied to lower WMT-Q scores at baseline, whereas PWC users improved in capacity and performance independent of baseline score. Delivering this training in a structured group format has a lower cost, which might improve adoption into clinical practice.

Efficacy of a Remote Train-the-Trainer Model for Wheelchair Skills Training Administered by Clinicians: A Cohort Study With Pre- vs Posttraining Comparisons.

OBJECTIVE: To test the hypotheses that remote training improves trainer confidence and when these trainers train others the capacity and confidence of the trainees improves. DESIGN: Cohort study with pre- vs posttraining comparisons. SETTING: Four spinal cord injury model systems centers. PARTICIPANTS: Convenience sample of 7 clinician trainers and 19 able-bodied trainees (N=26). INTERVENTIONS: Part 1 focused on trainer skill acquisition with self-study of the Wheelchair Skills Program Manual and instructional videos focused on motor learning, spotting, and 10 intermediate and advanced wheelchair skills. Trainers practiced in pairs, receiving asynchronous feedback on video recordings from a remote instructor. Part 2 included additional video modules targeted at "how to" assess and train others in 4 wheelchair skills: gets over obstacle, ascends low curb, ascends high curb with caregiver assistance, and performs stationary wheelie. Upon completion, the trainers each provided 1:1 in-person training for 2-3 trainees. MAIN OUTCOME MEASURES: Trainer confidence was assessed using the Self-Efficacy on Assessing, Training, and Spotting Test for Manual Wheelchairs. Trainee capacity ("Can you do it?") and confidence ("How confident are you?") were evaluated using the Wheelchair Skills Test Questionnaire (WST-Q). RESULTS: Trainer confidence increased for assessment (P=.003) and training (P=.002) but not spotting (P=.056). Trainee 4-item median (interquartile range) WST-Q scores significantly increased with training for capacity (13% [6-31] to 88% [75-88], P<.001) and confidence (13% [0-31] to 88% [81-100], P<.001). CONCLUSIONS: Remote training improves trainers' confidence with respect to wheelchair skills testing and training and the wheelchair skills capacity and confidence of their trainees.

Lifestyle physical activity in manual wheelchair users - an overlooked public health opportunity.

Public health guidelines and health promotion efforts have traditionally focused on weekly accumulation of moderate to vigorous physical activity (MVPA) via structured exercise. There has been a recent paradigm shift towards the organic incorporation of MVPA in daily leisure and non-leisure time, termed "Lifestyle Physical Activity" (LPA). However, this paradigm shift and the underlying research has neglected manual wheelchair users (MWCUs) with spinal cord injury (SCI), who could benefit from LPA. This article argues for expanding the LPA paradigm shift into research and health promotion efforts involving MWCUs with SCI. We suggest a working definition of LPA for MWCUs and candidate metrics for quantifying LPA. This is followed by brief overviews of LPA correlates, outcomes/consequences, and interventions and the need for theory based approaches to study these domains. We lastly suggest an approach for mitigating potential negative outcomes of increased LPA in MWCUs and suggest a research agenda.

Physical Activity Barriers in Danish Manual Wheelchair Users: A Cross-sectional Study.

OBJECTIVE: To identify physical activity barrier prevalence and severity among manual wheelchair users (MWCUs) and test whether barrier impact is associated with self-reported physical activity level (PAL). DESIGN: Cross-sectional survey. The Barriers to Physical Activity Questionnaire for People with Mobility Impairments (BPAQ-MI) was translated from English to Danish and administered online. The BPAQ-MI includes barriers within 4 domains and 8 subdomains and queries if an item hindered physical activity participation in the last 3 months (yes/no). If "yes," participants graded barrier severity from very small (1) to very big (5). Barrier impact scores were summed within and across domains. SETTING: General community. PARTICIPANTS: Danish MWCUs (N=181; 52.5% female, mean age, 48±14y.). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: PAL was rated from not active (1) to extremely active (10). Individual barrier prevalence (frequency, %) and severity (median [interquartile range]) was computed. Unadjusted (Spearman rank correlations, domains, subdomains) and adjusted (multivariate linear regression, subdomains) associations between PAL and barrier impact were computed. RESULTS: The 5 most prevalent barriers were reported by ≥49.6% of participants (2 intrapersonal and 3 community). The 5 most severe barriers all had a median of 5 (1 organizational and 4 community). Unadjusted analysis showed that PAL was inversely associated with total intrapersonal (r=-0.487, P<.01) and overall (r=-0.241, P<.01) impact and the intrapersonal "health" (r=-0.477, P<.01) and "beliefs/attitudes"(r=-0.307, P<.01) subdomains. Adjustment for shared variance revealed only the "health" subdomain impact score was independently associated with PAL (P<.001). CONCLUSIONS: Intrapersonal barriers were highly prevalent. Health-related barriers were inversely related to PAL. When organizational and community barriers were present, they were rated as particularly severe. These results provide novel information that can guide the design of future interventions aiming to increase MWCUs PALs.

Development and deployment of an at-home strength and conditioning program to support a phase I trial in persons with chronic spinal cord injury.

STUDY DESIGN: Nonrandomized clinical trial (NCT02354625). OBJECTIVES: As a part of a Phase I clinical trial to assess the safety of autologous human Schwann cells (ahSC) in persons with chronic spinal cord injury (SCI), participants engaged in a multimodal conditioning program pre- and post-ahSC transplantation. The program included a home-based strength and endurance training program to prevent lack of fitness and posttransplantation detraining from confounding potential ahSC therapeutic effects. This paper describes development, deployment, outcomes, and challenges of the home-based training program. SETTING: University-based laboratory. METHODS: Development phase: two men with paraplegia completed an 8-week laboratory-based 'test' of the home-based program. Deployment phase: the first four (two males, two females) participant cohort of the ahSC trial completed the program at home for 12 weeks pre and 20 weeks post ahSC transplant. RESULTS: Development phase: both participants improved their peak aerobic capacity (VO2peak) (≥17%), peak power output (POpeak) (≥8%), and time to exhaustion (TTE) (≥7%). Deployment phase: pretransplant training minimally increased fitness in the two male participants (≥6% POpeak and ≥9% TTE). The two women had no POpeak changes and slight TTE changes (+2.6 and -1.2%, respectively.) All four participants detrained during the posttransplant recovery period. After posttransplant retraining, all four participants increased TTE (4-24%), three increased VO2peak (≥11%), and two increased POpeak (≥7%). CONCLUSIONS: Home-based strength and condition programs can be effective and successfully included in therapeutic SCI trials. However, development of these programs requires substantial content knowledge and experience.

Case-Control Study of Ultrasound Evaluation of Acute Median Nerve Response to Upper Extremity Circuit Training in Spinal Cord Injury.

OBJECTIVE: Individuals with spinal cord injury (SCI) often present signs and symptoms of median nerve (MN) pathology. Preclinical signs identification of MN pathology might facilitate early intervention to prevent or delay carpal tunnel syndrome in SCI. We assessed if ultrasound parameters changed in response to upper extremity (UE) circuit training exercise in individuals with paraplegia and able-bodied individuals. DESIGN: Case-control study. PARTICIPANTS: Adults (N=32) with paraplegia (n=16) and age- and sex-matched able-bodied controls (n=16). INTERVENTION: Circuit training exercise. MAIN OUTCOME MEASURES: MN ultrasound evaluation at the pisiform and radius before and after UE exercise. Ultrasound parameters included cross-sectional area (CSA), and gray scale (GS). Data presented as mean ± SD. RESULTS: Pre-exercise CSAs were larger in SCI at the radius (12.0±2.9 vs 9.0±2.1; P=.003), but not the pisiform (9.8±3.1 vs 9.1±1.7; P=.431). There were no statistical differences in MN response to exercise between groups (all P≥.293). Across participants, CSA changes were inversely associated with their pre-exercise values at the pisiform (r=-0.648; P<.001) and the radius (r=-0.366; P=.043). Participants with pre-exercise CSA values ≥10.00 mm2 at the pisiform responded to exercise with decreases in CSA (mean change ± SD, -2.0±1.5; P=.002) and GS (-2.8±6.2; P=.029). Participants with pre-exercise CSA ≤9.99 mm2 at the pisiform responded to exercise with no change in CSA (mean change ± SD, 0.7±2.5; P=.002) and increased GS (3.2±7.2; P=.029). CONCLUSIONS: CSA exercise response was more strongly related to pre-exercise MN values than presence or absence of SCI.

Replication and novel analysis of age and sex effects on the neurologic and functional value of each spinal segment in the US healthcare setting.

STUDY DESIGN: Replication of previously developed prognostic model. OBJECTIVES: In motor complete injuries at admission to rehabilitation, perform; (1) replication analyses of the relationships between ISNCSCI motor level and motor scores and SCIM and (2) novel analyses to determine if age and/or sex moderate relationship between neurological impairment and function. SETTING: Admission to initial inpatient rehabilitation in the United States. METHODS: Post-Hoc analyses of data collected as part of a separate study. Replication analyses: (1) Pearson's correlation assessed relationship strength between neurologic impairment and function. (2) Multiple linear regression assessed if center or age influenced functional outcome. Novel analyses: (1) Moderated multiple regression assessed if age and/or sex moderated the lesion level-function relationship. RESULTS: Of the 406 datasets, 161 were motor complete injuries, and included in the analyses. Median time post injury at admission to rehabilitation was 19 days. Our replication analyses confirmed the neurologic and functional value of each spinal segment reported by the EM-SCI group (all p ≤ 0.018). We failed to confirm their reported age effect (p = 0.05) and non-effect of center (p = 0.037). Our novel analyses indicated that age coded as above/below 50 moderated the relationship between neurologic impairment and function (p = 0.038) in cervical injuries only, but that age coded as above/below 35 (all p ≥ 0.510) and sex (all p ≥ 0.465) did not. CONCLUSIONS: The neurological and functional value of each segment is consistent across very different healthcare settings in early and late sub-acute stages and minimally impacted by age and sex. Differences related to centers and age may confound efficacy trials. SPONSORSHIP: The Miami Project to Cure Paralysis; The Craig H. Neilsen Foundation (83492).

Interrater and intrarater reliability of ventilatory thresholds determined in individuals with spinal cord injury.

STUDY DESIGN: Cross-sectional. OBJECTIVES: Individualized training regimes are often based on ventilatory thresholds (VTs). The objectives were to study: (1) whether VTs during arm ergometry could be determined in individuals with spinal cord injury (SCI), (2) the intrarater and interrater reliability of VT determination. SETTING: University research laboratory. METHODS: Thirty graded arm crank ergometry exercise tests with 1-min increments of recreationally active individuals (tetraplegia (N = 11), paraplegia (N = 19)) were assessed. Two sports physicians assessed all tests blinded, randomly, in two sessions, for VT1 and VT2, resulting in 240 possible VTs. Power output (PO), heart rate (HR), and oxygen uptake (VO2) at each VT were compared between sessions or raters using paired samples t-tests, Wilcoxon signed-rank tests, intraclass correlation coefficients (ICC, relative agreement), and Bland-Altman plots (random error, absolute agreement). RESULTS: Of the 240 VTs, 217 (90%) could be determined. Of the 23 undetermined VTs, 2 (9%) were VT1 and 21 (91%) were VT2; 7 (30%) among individuals with paraplegia, and 16 (70%) among individuals with tetraplegia. For the successfully determined VTs, there were no systematic differences between sessions or raters. Intrarater and interrater ICCs for PO, HR, and VO2 at each VT were high to very high (0.82-1.00). Random error was small to large within raters, and large between raters. CONCLUSIONS: For VTs that could be determined, relative agreement was high to very high, absolute agreement varied. For some individuals, often with tetraplegia, VT determination was not possible, thus other methods should be considered to prescribe exercise intensity.

Relationship of Fitness and Wheelchair Mobility With Encounters, Avoidances, and Perception of Environmental Barriers Among Manual Wheelchair Users With Spinal Cord Injury.

OBJECTIVE: To assess (1) if fitness and mobility are related to behavior and perception of physical barriers and (2) if behavior and physical barrier perception are related. DESIGN: Cross-sectional case series. SETTING: Academic Medical Laboratory. PARTICIPANTS: Manual wheelchair users (N=50) with chronic spinal cord injury (62% paraplegia). INTERVENTION: None. MAIN OUTCOME MEASURES: Participants completed the following assessments: (1) fitness: graded exercise test (aerobic) and Wingate (anaerobic); (2) mobility: 6-minute push test and 30-second sprint test; (3) physical barrier behavior: Encounters of Environmental Features in the Environmental Aspects of Mobility Questionnaire (EAMQ); (4) physical barrier perception: Craig Hospital Inventory of Environmental Factor (CHIEF) Environmental Barriers domain. RESULTS: Individuals with paraplegia had higher fitness, mobility, and environmental barrier encounter rates and lower avoidance per encounter rates vs tetraplegia (all P≤.05). For individuals with tetraplegia only, as mobility and fitness increased, frequencies of (1) encounters increased; (2) avoidances per encounter decreased, in multiple EAMQ domains (all P≤.05). Perception of barriers did not differ between lesion levels (P=.79). Mobility and fitness were not related to environmental barriers perception in both groups (all P>.17). CONCLUSIONS: Fitness and mobility are associated with barrier behaviors (ie, encounters and avoidances) among individuals with tetraplegia, but not paraplegia. Despite a greater barrier avoidance rate, persons with tetraplegia do not perceive more physical barriers than persons with paraplegia. Surprisingly, fitness and mobility were not related to perception of barriers in either group. More research is required on if barrier perception, behavior, or both influence participation, to enable rehabilitation programs to tailor interventions to enhance participation.

Exercise Is Medicine Initiative: Physical Activity as a Vital Sign and Prescription in Adult Rehabilitation Practice.

To support rehabilitation health care professionals' efforts to increase physical activity levels among their outpatient rehabilitation and postdischarge patients, we review the Exercise is Medicine (EIM) initiative. The EIM initiative was launched in 2007 jointly by the American College of Sports Medicine and American Medical Association. Three principles underlie the EIM initiative. First, physical activity should be monitored as a vital sign; second, physical activity is an effective medical modality and should be prescribed; and third, success of their vision requires top down and bottom up efforts by 3 key stakeholder groups: health care providers, exercise professionals, and the community. The target weekly physical activity level is 150 minutes of moderate-to-vigorous physical activity, as established by the Centers for Disease Control and Prevention and World Health Organization. Persons falling below the weekly target physical activity level should be prescribed physical activity and/or referred to an exercise professional for implementation support. Selection of an exercise professional for referral is based on the patient's risk stratification and need to participate in clinically supervised physical activity.

Comparison of 1- Versus 3-Minute Stage Duration During Arm Ergometry in Individuals With Spinal Cord Injury.

OBJECTIVE: To investigate the effect of stage duration on peak physiological response to arm ergometry incremental exercise testing in individuals with spinal cord injury or disease (SCI/D) in support of developing a more individualized approach to testing. DESIGN: Parallel reliability study. SETTING: University research laboratory. PARTICIPANTS: Individuals with SCI/D (N=38) performed 2 peak oxygen consumption assessments comprised of 1-minute or 3-minute stages on 1 day. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Heart rate and oxygen consumption were recorded continuously from baseline through recovery. Every 1 minute or 3 minutes, resistance increased at an individualized level, and participants continued until volitional fatigue. The highest 30-second average was selected as peak oxygen consumption (Vo2peak) and peak heart rate. The highest workload achieved for ≥30 seconds was recorded as peak power output (PO). RESULTS: Intraclass correlation coefficients (ICCs) were >.95 for the following variables: absolute Vo2peak (mean ± SD, 1min: 1.2±0.7, 3min: 1.2±.62L/min; 95% CI, .91-.98), relative Vo2peak (mean ± SD, 1min: 16.6±9.4, 3min: 15.8±8.0mL/kg/min; 95% CI, .90-.98), absolute peak PO (mean ± SD, 1min: 61±41, 3min: 66±41W; 95% CI, .92-.98), and relative peak PO (mean ± SD, 1min: .80±56, 3min: .90±.55W/kg; 95% CI, .91-.98). There was no significant difference in peak heart rate between 3 minutes (132±27 beats per minute [bpm]) and 1 minute (130±28 bpm); however, the ICC lower limit was <.75 (0.67-0.90). Total test time was significantly longer in the 3-minute (8:17±2:52min:s) than in the 1-minute (6:29±2:21min:s) protocol. CONCLUSIONS: For measuring peak physiological values in an incremental arm ergometry test, stage duration is of little consequence because similar values were obtained for the main outcome measures in both protocols.

Effectiveness of Group Wheelchair Skills Training for People With Spinal Cord Injury: A Randomized Controlled Trial.

OBJECTIVE: To assess the effectiveness of group wheelchair skills training to elicit improvements in wheelchair skills. DESIGN: Randomized double-blinded controlled trial. SETTING: Four Spinal Cord Injury Model Systems Centers. PARTICIPANTS: Manual wheelchair users with spinal cord injury (N=114). INTERVENTION: Six 90-minute group Wheelchair Skills Training Program (WSTP) classes or two 1-hour active control sessions with 6 to 10 people per group. MAIN OUTCOME MEASURES: Baseline (t1) and 1-month follow-up (t2) Wheelchair Skills Test Questionnaire (WST-Q) (Version 4.2) for capacity and performance and Goal Attainment Scale (GAS) score. RESULTS: Follow-up was completed by 79 participants (WSTP: n=36, active control: n=43). No differences were found between missing and complete cases. Many users were highly skilled at baseline with a WST-Q capacity interquartile range of 77% to 97%. There were no differences between groups at baseline in WST-Q measures or demographics. Compared with the active control group, the WSTP group improved in WST-Q capacity advanced score (P=.02) but not in WST-Q capacity or WST-Q performance total scores (P=.068 and P=.873, respectively). The average GAS score (0% at t1) for the WSTP group at t2 was 65.6%±34.8%. Higher GAS scores and WST-Q capacity scores were found for those who attended more classes and had lower baseline skills. CONCLUSIONS: Group training can improve advanced wheelchair skills capacity and facilitate achievement of individually set goals. Lower skill levels at baseline and increased attendance were correlated with greater improvement.

Wheelchair Skills Capacity and Performance of Manual Wheelchair Users With Spinal Cord Injury.

OBJECTIVES: To describe the wheelchair skills capacity and performance of experienced manual wheelchair users with spinal cord injury (SCI) and to assess measurement properties of the Wheelchair Skills Test (WST) and Wheelchair Skills Test Questionnaire (WST-Q). DESIGN: Cross-sectional descriptive study involving within-subject comparisons. SETTING: Four Spinal Cord Injury Model Systems centers. PARTICIPANTS: Manual wheelchair users with SCI (N=117). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: WST and WST-Q version 4.2 as well as measures for Confidence, Basic Mobility, Independence, Ability to Participate, Satisfaction, and Pain Interference. RESULTS: The median (interquartile range) values for WST capacity, WST-Q capacity, and WST-Q performance were 81.0% (69.0%-90.0%), 88.0% (77.0%-97.0%), and 76.0% (66.3%-84.0%). The total WST capacity scores correlated significantly with the total WST-Q capacity scores (r=.76; P<.01) and WST-Q performance scores (r=.55; P<.01). The total WST-Q capacity and WST-Q performance scores were correlated significantly (r=.63; P<.001). Success rates were <75% for 10 of the 32 (31%) individual skills on the WST and 6 of the 32 (19%) individual skills on the WST-Q. Regression models for the total WST and WST-Q measures identified statistically significant predictors including age, sex, body mass index, and/or level of injury. The WST and WST-Q measures correlated significantly with the Confidence, Basic Mobility, Independence, or Pain Interference measures. CONCLUSIONS: Many people with SCI are unable to or do not perform some of the wheelchair skills that would allow them to participate more fully. More wheelchair skills training may enhance participation and quality of life of adults with SCI. The WST and WST-Q exhibit good content, construct, and concurrent validity.

Effects of prandial challenge on triglyceridemia, glycemia, and pro-inflammatory activity in persons with chronic paraplegia.

CONTEXT/OBJECTIVE: Exaggerated postprandial lipemia has been reported after spinal cord injury (SCI). We examined metabolite and accompanying pro-inflammatory biomarker responses to repeat feeding of typical high-fat meals in individuals with chronic paraplegia. DESIGN: Descriptive trial. METHODS: Metabolites (triglycerides, glucose, and insulin) and inflammatory biomarkers (interleukin-6 and high-sensitivity C-reactive protein (hsCRP)) were measured under fasting conditions in 11 recreationally active individuals with chronic (>1 year) paraplegia. Subjects received high-fat meals at time point 0 and again at minute 240. Antecubital venous blood was obtained at time points -30 (fasting), 0 (first meal), 30, 60, 90, 120, 240 (second meal), 360, and 480 minutes. Correlations were examined among the study variables. Exploratory subgroup analysis was performed for subjects with levels of postprandial glucose greater than >200 mg/dl. RESULTS: Triglycerides showed a significant rise 4 hours after eating. Basal inflammatory markers were elevated, and did not undergo additional change during the testing. Additionally, subjects with excessive postprandial glucose responses showed higher hsCRP levels than those having typical glucose responses both for fasting (11.8 ± 6.5 vs. 2.9 ± 2.7 mg/l, P = 0.064) and postprandial (11.1 ± 4.9 vs. 3.7 ± 3.8 mg/l, P = 0.018) values. CONCLUSIONS: Despite elevations in metabolic response markers, inflammatory markers did not change significantly after consumption of population-representative (i.e. hypercaloric) mixed-nutrient meals. Levels of fasting CRP in the high-risk range are consistent with other reports in persons with SCI and continue to pose concern for their cardiovascular disease risk. The possible association between postprandial metabolic responses and inflammatory states warrants further investigation to identify individual component risks for this secondary health hazard.

Ultrasound in Microsurgery: Current Applications and New Frontiers.

Ultrasound has revolutionized reconstructive microsurgery, offering real-time imaging and enhanced precision allowing for preoperative flap planning, recipient vessel identification and selection, postoperative flap monitoring, and lymphatic surgery. This narrative review of the literature provides an updated evidence-based overlook on the current applications and emerging frontiers of ultrasound in microsurgery, focusing on free tissue transfer and lymphatic surgery. Color duplex ultrasound (CDU) plays a pivotal role in preoperative flap planning and design, providing real-time imaging that enables detailed perforator mapping, perforator suitability assessment, blood flow velocity measurement, and, ultimately, flap design optimization. Ultrasound also aids in recipient vessel selection by providing assessment of caliber, patency, location, and flow velocity of recipient vessels. Postoperatively, ultrasound enables real-time monitoring of flap perfusion, providing early detection of potential flap compromise and improved flap survival rates. In lymphatic surgery, ultra-high frequency ultrasound (UHFUS) offers precise mapping and evaluation of lymphatic vessels, improving efficacy and efficiency by targeting larger dilated vessels. Integrating ultrasound into reconstructive microsurgery represents a significant advancement in the utilization of imaging in the field. With growing accessibility of devices, improved training, and technological advancements, using ultrasound as a key imaging tool offers substantial potential for the evolution of reconstructive microsurgery.

Blood-stage malaria vaccine candidate RH5.1/Matrix-M in healthy Tanzanian adults and children; an open-label, non-randomised, first-in-human, single-centre, phase 1b trial.

BACKGROUND: A blood-stage Plasmodium falciparum malaria vaccine would provide a second line of defence to complement partially effective or waning immunity conferred by the approved pre-erythrocytic vaccines. RH5.1 is a soluble protein vaccine candidate for blood-stage P falciparum, formulated with Matrix-M adjuvant to assess safety and immunogenicity in a malaria-endemic adult and paediatric population for the first time. METHODS: We did a non-randomised, phase 1b, single-centre, dose-escalation, age de-escalation, first-in-human trial of RH5.1/Matrix-M in Bagamoyo, Tanzania. We recruited healthy adults (aged 18-45 years) and children (aged 5-17 months) to receive the RH5.1/Matrix-M vaccine candidate in the following three-dose regimens: 10 µg RH5.1 at 0, 1, and 2 months (Adults 10M), and the higher dose of 50 µg RH5.1 at 0 and 1 month and 10 µg RH5.1 at 6 months (delayed-fractional third dose regimen; Adults DFx). Children received either 10 µg RH5.1 at 0, 1, and 2 months (Children 10M) or 10 µg RH5.1 at 0, 1, and 6 months (delayed third dose regimen; Children 10D), and were recruited in parallel, followed by children who received the dose-escalation regimen (Children DFx) and children with higher malaria pre-exposure who also received the dose-escalation regimen (High Children DFx). All RH5.1 doses were formulated with 50 µg Matrix-M adjuvant. Primary outcomes for vaccine safety were solicited and unsolicited adverse events after each vaccination, along with any serious adverse events during the study period. The secondary outcome measures for immunogenicity were the concentration and avidity of anti-RH5.1 serum IgG antibodies and their percentage growth inhibition activity (GIA) in vitro, as well as cellular immunogenicity to RH5.1. All participants receiving at least one dose of vaccine were included in the primary analyses. This trial is registered at ClinicalTrials.gov, NCT04318002, and is now complete. FINDINGS: Between Jan 25, 2021, and April 15, 2021, we recruited 12 adults (six [50%] in the Adults 10M group and six [50%] in the Adults DFx group) and 48 children (12 each in the Children 10M, Children 10D, Children DFx, and High Children DFx groups). 57 (95%) of 60 participants completed the vaccination series and 55 (92%) completed 22 months of follow-up following the third vaccination. Vaccinations were well-tolerated across both age groups. There were five serious adverse events involving four child participants during the trial, none of which were deemed related to vaccination. RH5-specific T cell and serum IgG antibody responses were induced by vaccination and purified total IgG showed in vitro GIA against P falciparum. We found similar functional quality (ie, GIA per µg RH5-specific IgG) across all age groups and dosing regimens at 14 days after the final vaccination; the concentration of RH5.1-specific polyclonal IgG required to give 50% GIA was 14·3 µg/mL (95% CI 13·4-15·2). 11 children were vaccinated with the delayed third dose regimen and showed the highest median anti-RH5 serum IgG concentration 14 days following the third vaccination (723 µg/mL [IQR 511-1000]), resulting in all 11 who received the full series showing greater than 60% GIA following dilution of total IgG to 2·5 mg/mL (median 88% [IQR 81-94]). INTERPRETATION: The RH5.1/Matrix-M vaccine candidate shows an acceptable safety and reactogenicity profile in both adults and 5-17-month-old children residing in a malaria-endemic area, with all children in the delayed third dose regimen reaching a level of GIA previously associated with protective outcome against blood-stage P falciparum challenge in non-human primates. These data support onward efficacy assessment of this vaccine candidate against clinical malaria in young African children. FUNDING: The European and Developing Countries Clinical Trials Partnership; the UK Medical Research Council; the UK Department for International Development; the National Institute for Health and Care Research Oxford Biomedical Research Centre; the Division of Intramural Research, National Institute of Allergy and Infectious Diseases; the US Agency for International Development; and the Wellcome Trust.

Relationship between rolling resistance, preferred speed, and manual wheelchair propulsion mechanics in non-disabled adults.

PURPOSE: To characterize the relationship among rolling resistance (RR), preferred speed, and propulsion mechanics. METHODS: N = 11 non-disabled individuals (mean (SD)); Age 24 years (2), BMI 23.8 kg/m2 (4.3) completed a submaximal graded wheelchair exercise test (GXTsubmax, fixed speed, terminated at Rating of Perceived Effort (RPE)=8 (0-10 scale)) and a single-blind, within-subject repeated measures wheelchair propulsion experiment (RME). RR at RPE = 10 (estimated maximum workload, Maxestimated) was estimated from the GXTsubmax RPE-RR relationship. RME consisted of N = 19 1-minute trials (self-selected speed) each followed by 2-minutes rest. The trials included N = 16 unique RR between 25-100% of Maxestimated. Averages of all pushes in N = 16 unique 1-minute trials were computed for average RR (N), speed (m/s), peak force (Fpeak (N)), force rate of rise (Fror (N/s)), push frequency (PF (pushes/min)), and push length (PL (deg)). RESULTS: Repeated measures correlation assessed relationships among outcome variables (α = 0.05). RR was associated with decreased speed (r=-0.81, p < 0.001), increased Fpeak (r = 0.92), Fror (r = 0.26), and PL (r = 0.32) (all p > 0.001), and unrelated to PF (r = 0.02, p = 0.848). Increased speed was associated with increased Fror (r = 0.23, p = 0.003) and PF (r = 0.27, p < 0.001) and decreased Fpeak (r=-0.66, p < 0.001) and PL (r=-0.25, p < 0.001). CONCLUSION: Increasing RR increases Fpeak despite reducing self-selected speed. RR and speed were strongly and moderately related to Fpeak, respectively, but weakly related to other propulsion mechanics. These results suggest that reducing user-system RR may confer dual benefits of improved mobility and decreased upper extremity loading. Further testing among wheelchair users is required. Clinical trial registration number: NCT04987177.

To our knowledge, this is the first study to directly characterize the dose-response relationship between rolling resistance and manual wheelchair propulsion biomechanics. By characterizing the relationship between rolling resistance and propulsion mechanics, more objective and accurate clinical interventions can be assessed/implemented.Our results suggest that reducing the user-wheelchair system rolling resistance should decrease peak forces, which is favorable, as increased peak forces have been linked to upper extremity pain and pathology.Our findings of weak relationships between rolling resistance and push length, push frequency, and force rate of rise, suggest that reductions in rolling resistance may not be the optimal method for "improving" these variables. Propulsion training has been shown to achieve long-term favorable changes in these variables, so an area for future work can be to evaluate if reducing rolling resistance or propulsion training is more effective at "improving" these variables.The strong relationship we observed between rolling resistance and self-selected speed, suggests that user-wheelchair system rolling resistance reductions might encourage increased mobility in the home and community, theoretically improving participation and thus quality of life.

A novel approach to directly measuring wheel and caster rolling resistance accurately predicts user-wheelchair system-level rolling resistance.

Introduction: Clinical practice guidelines for preservation of upper extremity recommend minimizing wheelchair propulsion forces. Our ability to make quantitative recommendations about the effects of wheelchair configuration changes is limited by system-level tests to measure rolling resistance (RR). We developed a method that directly measures caster and propulsion wheel RR at a component-level. The study purpose is to assess accuracy and consistency of component-level estimates of system-level RR. Methods: The RR of N = 144 simulated unique wheelchair-user systems were estimated using our novel component-level method and compared to system-level RR measured by treadmill drag tests, representing combinations of caster types/diameters, rear wheel types/diameters, loads, and front-rear load distributions. Accuracy was assessed by Bland-Altman limits of agreement (LOA) and consistency by intraclass correlation (ICC). Results: Overall ICC was 0.94, 95% CI [0.91-0.95]. Component-level estimates were systematically lower than system-level (-1.1 N), with LOA +/-1.3 N. RR force differences between methods were constant over the range of test conditions. Conclusion: Component-level estimates of wheelchair-user system RR are accurate and consistent when compared to a system-level test method, evidenced by small absolute LOA and high ICC. Combined with a prior study on precision, this study helps to establish validity for this RR test method.

Pain interference, pain type, and quality of life among adults with spina bifida.

INTRODUCTION: Individuals with spina bifida (SB) experience nociceptive and neuropathic pain, and women with SB report more pain. However, the relationship between pain type and gender on pain interference and quality of life (QoL) among individuals with SB is less understood. OBJECTIVE: To assess relationships among pain interference, pain quality, participation-related QoL, and gender among adults with SB. DESIGN: Fifty-one adults with SB completed a self-report survey assessing SB characteristics, pain severity, pain type, pain interference, and QoL. SETTING: Hospital outpatient adult SB clinic. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Measures of nociceptive pain quality, neuropathic pain quality, participation-related QoL, as well as pain interference with general activities, mood, and sleep were selected a priori as study measures. RESULTS: Fifty-eight percent (N = 30) reported pain and more women than men reported pain (69% vs. 38%, p = .003). Higher general pain interference was associated with lower QoL (r = 0.444, p = .042), but not mood or sleep pain interference (both p's ≥ .451). There was no statistically significant difference in pain interference between genders (p = .138). Nociceptive pain was more common. Levels of nociceptive pain were positively associated with general pain interference, sleep pain interference, and mood pain inference. Neither pain type was associated with QoL (both p's > .082). CONCLUSIONS: The results from this study reveal key differences/similarities among four interrelated factors: pain, pain interference, QoL, and gender. Pertinent information gathered on pain type and QoL, like increased prevalence of nociceptive pain, can be utilized to formulate proactive and effective treatment plans for individuals with SB that may benefit their sleep pain interference and mood pain interference.