Lifelong Fitness in Ambulatory Children and Adolescents with Cerebral Palsy I: Key Ingredients for Bone and Muscle Health.

Physical activity of a sufficient amount and intensity is essential to health and the prevention of a sedentary lifestyle in all children as they transition into adolescence and adulthood. While fostering a fit lifestyle in all children can be challenging, it may be even more so for those with cerebral palsy (CP). Evidence suggests that bone and muscle health can improve with targeted exercise programs for children with CP. Yet, it is not clear how musculoskeletal improvements are sustained into adulthood. In this perspective, we introduce key ingredients and guidelines to promote bone and muscle health in ambulatory children with CP (GMFCS I-III), which could lay the foundation for sustained fitness and musculoskeletal health as they transition from childhood to adolescence and adulthood. First, one must consider crucial characteristics of the skeletal and muscular systems as well as key factors to augment bone and muscle integrity. Second, to build a better foundation, we must consider critical time periods and essential ingredients for programming. Finally, to foster the sustainability of a fit lifestyle, we must encourage commitment and self-initiated action while ensuring the attainment of skill acquisition and function. Thus, the overall objective of this perspective paper is to guide exercise programming and community implementation to truly alter lifelong fitness in persons with CP.

Lifelong Fitness in Ambulatory Children and Adolescents with Cerebral Palsy II: Influencing the Trajectory.

Physical activity of at least moderate intensity in all children contributes to higher levels of physical and psychological health. While essential, children with cerebral palsy (CP) often lack the physical capacity, resources, and knowledge to engage in physical activity at a sufficient intensity to optimize health and well-being. Low levels of physical activity place them at risk for declining fitness and health, contributing to a sedentary lifestyle. From this perspective, we describe a framework to foster a lifelong trajectory of fitness in ambulatory children with CP (GMFCS I-III) as they progress into adolescence and adulthood, implemented in conjunction with a training program to augment bone and muscle health. First, we recommend that altering the fitness trajectory of children with CP will require the use of methods to drive behavioral change prior to adolescence. Second, to promote behavior change, we suggest embedding lifestyle intervention into fitness programming while including meaningful activities and peer socialization to foster self-directed habit formation. If the inclusion of lifestyle intervention to drive behavior change is embedded into fitness programs and found to be effective, it may guide the delivery of targeted programming and community implementation. Participation in comprehensive programming could alter the long-term trajectory of musculoskeletal health while fostering strong self-efficacy in persons with CP.

Quantifying intra- and interlimb use during unimanual and bimanual tasks in persons with hemiparesis post-stroke.

BACKGROUND: Individuals with hemiparesis post-stroke often have difficulty with tasks requiring upper extremity (UE) intra- and interlimb use, yet methods to quantify both are limited. OBJECTIVE: To develop a quantitative yet sensitive method to identify distinct features of UE intra- and interlimb use during task performance. METHODS: Twenty adults post-stroke and 20 controls wore five inertial sensors (wrists, upper arms, sternum) during 12 seated UE tasks. Three sensor modalities (acceleration, angular rate of change, orientation) were examined for three metrics (peak to peak amplitude, time, and frequency). To allow for comparison between sensor data, the resultant values were combined into one motion parameter, per sensor pair, using a novel algorithm. This motion parameter was compared in a group-by-task analysis of variance as a similarity score (0-1) between key sensor pairs: sternum to wrist, wrist to wrist, and wrist to upper arm. A use ratio (paretic/non-paretic arm) was calculated in persons post-stroke from wrist sensor data for each modality and compared to scores from the Adult Assisting Hand Assessment (Ad-AHA Stroke) and UE Fugl-Meyer (UEFM). RESULTS: A significant group × task interaction in the similarity score was found for all key sensor pairs. Post-hoc tests between task type revealed significant differences in similarity for sensor pairs in 8/9 comparisons for controls and 3/9 comparisons for persons post stroke. The use ratio was significantly predictive of the Ad-AHA Stroke and UEFM scores for each modality. CONCLUSIONS: Our algorithm and sensor data analyses distinguished task type within and between groups and were predictive of clinical scores. Future work will assess reliability and validity of this novel metric to allow development of an easy-to-use app for clinicians.

Highlighting gaps in spinal cord injury research in activity-based interventions for the upper extremity: A scoping review.

BACKGROUND: Upper extremity activity-based therapy for neurologic disorders employs high-intensity, high repetition functional training to exploit neuroplasticity and improve function. Research focused on high-intensity upper extremity activity-based therapy for persons with spinal cord injury (SCI) is limited. OBJECTIVE: To summarize high-intensity activity-based interventions used in neurological disorders for their current or potential application to SCI. METHODS: The scoping review included articles from MEDLINE, CINAHL, Cochrane CENTRAL, and OTSeeker with the criteria: non-invasive activity-based interventions delivered at least three times/week for two weeks, upper extremity functional outcomes, age 13 years or older, English language, and neurological disorders three months post onset/injury. RESULTS: The search yielded 172 studies. There were seven studies with SCI, all in adults. Activity-based interventions in SCI included task-specific training and gaming, with and without electrical stimulation, and a robotic exoskeleton. The other populations found in the review included studies in stroke, cerebral palsy, and multiple sclerosis. Thirty-four different interventions were reported in other populations. In comparison to the extensive stroke research, work in SCI was not found for high-intensity interventions using virtual reality, brain stimulation, rehabilitation devices, and applications to the home and telerehab settings. CONCLUSION: The results highlight critical gaps within upper extremity high-intensity activity-based research in SCI.

Durability of response to VGX-3100 treatment of HPV16/18 positive cervical HSIL.

VGX-3100 is an investigational DNA-based immunotherapy being developed as an alternative to surgery and ablation for cervical High-Grade Squamous Intraepithelial Lesion (HSIL) with the aim of preserving reproductive health while treating precancerous disease. Response durability up to 1.5 y following dosing is now reported.Histologic regression and HPV16 and/or HPV 18 (HPV16/18) clearance were previously demonstrated in a randomized, placebo-controlled, double-blind trial and reported for 6 months after the last dose of VGX-3100 or placebo. The presence of HPV16/18, Pap smear diagnoses, and immunogenicity longer-term responses were assessed at 18 months after the last dose.91% (32/35) VGX-3100-treated women, whose cervical HSIL regressed and avoided excision at 6 months following study treatment completion, had no detectable HPV16/18 at 18 months following treatment completion. These results were comparable to those for women who received placebo and then later underwent surgery. For VGX-3100 recipients who regressed at 6 months following study treatment completion and avoided excision during the trial, Pap testing showed no HSIL recurrence at 18 months following VGX-3100 treatment. VGX-3100-induced cellular immune responses specific for HPV 16/18 E6/E7 remained higher than for placebo control recipients at 18 months.In women with cervical HSIL who responded to VGX-3100 and were able to avoid surgery, clinical outcomes were comparable to the placebo control group which underwent conventional surgical treatment. These findings extend the understanding of the durability of the treatment effect of VGX-3100 up to 1.5 y and support that VGX-3100 could be used as an alternative to surgery.

Complex Enterally Tube-Fed Community Patients Display Stable Tolerance, Improved Compliance and Better Achieve Energy and Protein Targets with a High-Energy, High-Protein Peptide-Based Enteral Tube Feed: Results from a Multi-Centre Pilot Study.

This pilot study evaluated a high-energy, high-protein, peptide-based, (medium-chain triglycerides) MCT-containing enteral tube feed (Nutrison Peptisorb Plus HEHP®, Nutricia Ltd., Trowbridge, BA14 0XQ, UK.) containing 1.5 kcal/mL and 7.5 g protein/100 mL. Fifteen community-based, enterally tube-fed adults (42 (SD 16.3) years) received the intervention feed daily for 28 days, with gastrointestinal tolerance, compliance and nutrient intake assessed at baseline and after the intervention period. Incidence and intensity of constipation (p = 0.496), nausea (p = 1.000), abdominal pain (p = 0.366) and bloating (p = 0.250) remained statistically unchanged, yet the incidence and intensity of diarrhoea improved significantly after receiving the intervention feed (Z = -2.271, p = 0.023). Compliance with the intervention feed was significantly greater compared to the patient's baseline regimens (99% vs. 87%, p = 0.038). Compared to baseline, use of the intervention feed enabled patients to significantly increase total energy (1676 kcal/day (SD 449) to 1884 kcal/day (SD 537), p = 0.039) and protein intake (73 g/day (SD 17) to 89 g/day (SD 23), p = 0.001), allowing patients to better achieve energy (from 88% to 99%, p = 0.038) and protein (from 101% to 121%, p < 0.001) requirements. This pilot study demonstrates that a high-energy, high-protein, peptide-based, MCT-containing enteral tube feed maintains gastrointestinal tolerance and improves compliance, energy and protein intake in complex, enterally tube-fed, community-based adult patients, though more work is recommended to confirm this.

Comparison of Machine Learning approaches for Classifying Upper Extremity Tasks in Individuals Post-Stroke.

After a stroke, individuals often exhibit upper extremity (UE) motor dysfunction, influencing the performance of everyday tasks. Characterizing UE movements is useful to track recovery and response to intervention. Yet, due to the complexity of the recovery process, UE movements may be extremely variable and person-specific. While this renders automatic recognition of these gestures challenging, machine learning methods could be used to classify UE movements in atypical populations. In the current study, we utilize data from 20 individuals post-stroke and 20 age-matched controls to identify an optimal set of sensor-extracted features for the classification of unimanual and bimanual gestures during task performance. We found that using fewer than 100 features along with a random forest classifier produced the best performance across both groups, with both user-dependent and user-independent models.

Immunotherapy Targeting HPV16/18 Generates Potent Immune Responses in HPV-Associated Head and Neck Cancer.

PURPOSE: Clinical responses with programmed death (PD-1) receptor-directed antibodies occur in about 20% of patients with advanced head and neck squamous cell cancer (HNSCCa). Viral neoantigens, such as the E6/E7 proteins of HPV16/18, are attractive targets for therapeutic immunization and offer an immune activation strategy that may be complementary to PD-1 inhibition. PATIENTS AND METHODS: We report phase Ib/II safety, tolerability, and immunogenicity results of immunotherapy with MEDI0457 (DNA immunotherapy targeting HPV16/18 E6/E7 with IL12 encoding plasmids) delivered by electroporation with CELLECTRA constant current device. Twenty-two patients with locally advanced, p16+ HNSCCa received MEDI0457. RESULTS: MEDI0457 was associated with mild injection site reactions, but no treatment-related grade 3-5 adverse events (AE) were noted. Eighteen of 21 evaluable patients showed elevated antigen-specific T-cell activity by IFNγ ELISpot, and persistent cellular responses surpassing 100 spot-forming units (SFUs)/106 peripheral blood mononuclear cells (PBMCs) were noted out to 1 year. Induction of HPV-specific CD8+ T cells was observed. MEDI0457 shifted the CD8+/FoxP3+ ratio in 4 of 5 post immunotherapy tumor samples and increased the number of perforin+ immune infiltrates in all 5 patients. One patient developed metastatic disease and was treated with anti-PD-1 therapy with a rapid and durable complete response. Flow-cytometric analyses revealed induction of HPV16-specific PD-1+ CD8+ T cells that were not found prior to MEDI0547 (0% vs. 1.8%). CONCLUSIONS: These data demonstrate that MEDI0457 can generate durable HPV16/18 antigen-specific peripheral and tumor immune responses. This approach may be used as a complementary strategy to PD-1/PD-L1 inhibition in HPV-associated HNSCCa to improve therapeutic outcomes.

Development of Sensor-Based Measures of Upper Extremity Interlimb Coordination.

The development of motor impairment after the onset of an injury such as stroke may result in long-term compensatory behaviors. Because compensation often evolves in ambient settings (outside the purview of monitoring clinicians), there is a need for quantitative tools capable of accurately detecting the subtleties of compensation and related reduction in interlimb coordination. Improvement in interlimb coordination may serve as a marker of recovery from stroke, and rehabilitation progress. The current study investigates measures of upper extremity interlimb coordination in persons post-stroke and healthy controls. It introduces a novel algorithm for objective characterization of interlimb coordination during the performance of real-world tasks.

Activity-based Rehabilitation Interventions of the Neurologically Impaired Upper Extremity: Description of a Scoping Review Protocol.

Introduction: A scoping review provides a means to synthesize and present a large body of literature on a broad topic, such as methods for various upper extremity activity-based therapy (ABT) interventions. Objectives: To describe our scoping review protocol to evaluate peer-reviewed articles focused on ABT interventions for individuals with neurologically impaired upper extremities. Methods: At Jefferson College of Health Professions and Sidney Kimmel Medical College at Jefferson, Philadelphia, the authors will follow this protocol to conduct a scoping review by establishing a research question and conducting a search of bibliographic databases to identify relevant studies. Using specific inclusion and exclusion criteria, abstracts will be screened and full-text articles will be reviewed for inclusion in charting, summarizing, and reporting results of appropriate studies. Conclusion: This protocol will guide the scoping review process to develop a framework for establishing a noninvasive ABT intervention informed by evidence for individuals with neurologically impaired upper extremities.

Innovative evaluation of dexterity in pediatrics.

STUDY DESIGN: Review paper. INTRODUCTION: Hand dexterity is multifaceted and essential to the performance of daily tasks. Timed performance and precision demands are the most common features of quantitative dexterity testing. Measurement concepts such as rate of completion, in-hand manipulation and dynamic force control of instabilities are being integrated into assessment tools for the pediatric population. PURPOSE: To review measurement concepts inherent in pediatric dexterity testing and introduce concepts that are infrequently measured or novel as exemplified with two assessment tools. METHODS: Measurement concepts included in common assessment tools are introduced first. We then describe seldom measured and novel concepts embedded in two instruments; the Functional Dexterity Test (FDT) and the Strength-Dexterity (SD) Test. DISCUSSION: The inclusion of novel yet informative tools and measurement concepts in our assessments could aid our understanding of atypical dexterity, and potentially contribute to the design of targeted therapy programs.

Clinical assessment of the infant and child following perinatal brachial plexus injury.

STUDY DESIGN: Literature review. INTRODUCTION: After perinatal brachial plexus injury (PBPI), clinicians play an important role in injury classification as well as the assessment of recovery and secondary conditions. Early assessment guides the initial plan of care and influences follow-up and long-term outcome. PURPOSE: To review methods used to assess, classify and monitor the extent and influence of PBPI with an emphasis on guidelines for clinicians. METHODS: We use The International Classification of Functioning, Disability, and Health (ICF) model to provide a guide to assessment after PBPI for rehabilitation clinicians. DISCUSSION: With information gained from targeted assessments, clinicians can design interventions to increase the opportunities infants and children have for optimal recovery and to attain skills that allow participation in areas of interest.

Interrater reliability of the Wolf Motor Function Test-Functional Ability Scale: why it matters.

BACKGROUND: One important objective for clinical trialists in rehabilitation is determining efficacy of interventions to enhance motor behavior. In part, limitation in the precision of measurement presents a challenge. The few valid, low-cost observational tools available to assess motor behavior cannot escape the variability inherent in test administration and scoring. This is especially true when there are multiple evaluators and raters, as in the case of multisite randomized controlled trials (RCTs). One way to enhance reliability and reduce variability is to implement rigorous quality control (QC) procedures. OBJECTIVE: This article describes a systematic QC process used to refine the administration and scoring procedures for the Wolf Motor Function Test (WMFT)-Functional Ability Scale (FAS). METHODS: The QC process, a systematic focus-group collaboration, was developed and used for a phase III RCT, which enlisted multiple evaluators and an experienced WMFT-FAS rater panel. RESULTS: After 3 staged refinements to the administration and scoring instructions, we achieved a sufficiently high interrater reliability (weighted κ = 0.8). CONCLUSIONS AND IMPLICATIONS: A systematic focus-group process was shown to be an effective method to improve reliability of observational assessment tools for motor behavior in neurorehabilitation. A reduction in noise-related variability in performance assessments will increase power and potentially lower the number needed to treat. Improved precision of measurement can lead to more cost-effective and efficient clinical trials. Finally, we suggest that improved precision in measures of motor behavior may provide more insight into recovery mechanisms than a single measure of movement time alone.

Defining the role of sensation, strength, and prehension for upper limb function in cervical spinal cord injury.

BACKGROUND: Upper limb function plays a significant role in enhancing independence for individuals with tetraplegia. However, there is limited knowledge about the specific input of sensorimotor deficits on upper limb function. Thus the theoretical framework designed to develop the Graded Redefined Assessment of Strength Sensibility and Prehension (GRASSP) was used as a hypothetical model to analyze the impact of impairment on function. OBJECTIVE: To define the association of impairment (sensation, strength, and prehension measured by the GRASSP) to upper limb function as defined by functional measures (Capabilities of Upper Extremity Questionnaire, Spinal Cord Independence Measure). METHODS: A hypothetical model representing relationships by applying structural equation modeling was used to estimate the effect of the impairment domains in GRASSP on upper limb function. Data collected on 72 chronic individuals with tetraplegia was used to test the hypothetical model. RESULTS: Structural equation modeling confirmed strong associations between sensation, strength, and prehension with upper limb function, and determined 72% of the variance in "sensorimotor upper limb function" was explained by the model. Statistics of fit showed the data did fit the hypothesized model. Sensation and strength influence upper limb function directly and indirectly with prehension as the mediator. CONCLUSIONS: The GRASSP is a sensitive diagnostic tool in distinguishing the relative contribution of strength, sensation and prehension to function. Thus, the impact of interventions on specific domains of impairment and related contribution on clinical recovery of the upper limb can be detailed to optimize rehabilitation programs.

Applying principles of motor learning and control to upper extremity rehabilitation.

The purpose of this article is to provide a brief review of the principles of motor control and learning. Different models of motor control from historical to contemporary are presented with emphasis on the Systems model. Concepts of motor learning including skill acquisition, measurement of learning, and methods to promote skill acquisition by examining the many facets of practice scheduling and use of feedback are provided. A fictional client case is introduced and threaded throughout the article to facilitate understanding of these concepts and how they can be applied to clinical practice.