Dual utilization of Medicare and VA outpatient care among Veterans with spinal cord injuries and disorders.

OBJECTIVE: Veterans with spinal cord injuries and disorders (SCI/D) utilizing Veterans Affairs healthcare facilities are also Medicare eligible. Use of multiple health care systems potentially duplicates or fragments care in this population; yet little is known about those using multiple systems. This study describes dual use of services paid for by VA and Medicare among Veterans with SCI/D. DESIGN: Retrospective, cross-sectional, observational study. PARTICIPANTS: Veterans with SCI/D (n = 13,902) who received healthcare services within the VA SCI System of Care and were eligible for or enrolled in Medicare in 2011. INTERVENTIONS: N/A. OUTCOME MEASURES: Patient characteristics, average number of visits and patient level frequencies of reasons for visits were determined for individuals within healthcare utilization (VA only, Medicare only, or dual VA/Medicare) groups. Multinomial logistic regression analyses were used to investigate associations of patient variables on dual use. RESULTS: 65.3% of Veterans with SCI/D were VA only users for outpatient encounters, 4.4% had encounters paid for by Medicare only, and 30.3% were dual users. Veterans were less likely to be VA only users if they were older than 69 and if they had been injured for greater than ten years. African American Veterans with SCI (compared to white) were more likely to be VA only users. CONCLUSION: A substantial number (∼30%) of Veterans with SCI/D are dual users. These numbers highlight the importance of improved strategies to coordinate care and increase health information sharing across systems.

Sensor acquired reachable workspace in the elderly population: A cross-sectional observational study.

The elderly population experiences a decline in upper extremity range of motion (ROM), impairing activities of daily living. The primary mode of quantification is by goniometer measurement. In this cross-sectional observation study, we investigate a sensor-acquired reachable workspace for assessing shoulder ROM decline in an elderly population in comparison to traditional measurements. Sixty-one healthy subjects aged ≥ 65 years were included and compared to a cohort of 39 younger subjects, aged 20 to 64. A sensor acquired reachable workspace using a Kinect motion capture camera measured the maximum reaching ability of both arms while in a seated position, measured in m2 and normalized to arm length to calculate a novel score defined as a relative surface area. This score approximates range of motion in the upper extremity. This measurement was compared to goniometer measurements, including active ROM in shoulder flexion and abduction. Total RSA shows moderate to strong correlation between goniometer in flexion and abduction in the dominant arm (R = 0.790 and R = 0.650, P < .001, respectively) and moderate correlations for the nondominant arm (R = 0.622 and R = 0.615, P < .001). Compared to the younger cohort, the elderly population demonstrated significantly reduced total RSA in the dominant arm (meanelderly = 0.774, SD = 0.09; meanyounger = 0.830, SD = 0.07, P < .001), with significant reductions in the upper lateral quadrant in both arms (dominant: meanelderly = 0.225, SD = 0.04; meanyounger = 0.241, SD = 0.01; P < .001; nondominant: meanelderly = 0.213, SD = 0.03; meanyounger = 0.228, SD = 0.01; P = .004). The test-retest reliability was strong for both dominant and nondominant total RSA (ICC > 0.762). The reachable workspace demonstrates promise as a simple and quick tool for clinicians to assess detailed and quantitative active shoulder ROM decline in the elderly population.

Quantitative Muscle Analysis in FSHD Using Whole-Body Fat-Referenced MRI: Composite Scores for Longitudinal and Cross-sectional Analysis.

BACKGROUND AND OBJECTIVES: Facioscapulohumeral muscular dystrophy (FSHD) is a rare, debilitating disease characterized by progressive muscle weakness. MRI is a sensitive assessment of disease severity and progression. We developed a quantitative whole-body (WB) musculoskeletal MRI (WB-MSK-MRI) protocol analyzing muscles in their entirety. This study aimed to assess WB-MSK-MRI as a potential imaging biomarker providing reliable measurements of muscle health that capture disease heterogeneity and clinically meaningful composite assessments correlating with severity and more responsive to change in clinical trials. METHODS: Participants aged 18-65 years, with genetically confirmed FSHD1, clinical severity 2 to 4 (Ricci scale, range 0-5), and ≥1 short tau inversion recovery-positive lower extremity muscle eligible for needle biopsy, enrolled at 6 sites and were imaged twice 4-12 weeks apart. Volumetric analysis of muscle fat infiltration (MFI), muscle fat fraction (MFF), and lean muscle volume (LMV) in 18 (36 total) muscles from bilateral shoulder, proximal arm, trunk, and legs was performed after automated atlas-based segmentation, followed by manual verification. A WB composite score, including muscles at highest risk for progression, and functional cross-sectional composites for correlation with relevant functional outcomes including timed up and go (TUG), FSHD-TUG, and reachable workspace (RWS), were developed. RESULTS: Seventeen participants enrolled in this study; 16 follow-up MRIs were performed at 52 days (range 36-85 days). Functional cross-sectional composites (MFF and MFI) showed moderate to strong correlations: TUG (ρ = 0.71, ρ = 0.83), FSHD-TUG (ρ = 0.73, ρ = 0.73), and RWS (left arm: ρ = -0.71, ρ = -0.53; right arm: ρ = -0.61, ρ = -0.65). WB composite variability: LMVtot, coefficient of variation (CV) 1.9% and 3.4%; MFFtot, within-subject SD (Sw) 0.5% and 1.5%; and MFItot (Sw), 0.3% and 0.4% for normal and intermediate muscles, respectively. CV and Sw were higher in intermediate (MFI ≥0.10; MFF <0.50) than in normal (MFI <0.10, MFF <0.50) muscles. DISCUSSION: We developed a WB-MSK-MRI protocol and composite measures that capture disease heterogeneity and assess muscle involvement as it correlates with FSHD-relevant clinical endpoints. Functional composites robustly correlate with functional assessments. Stability of the WB composite shows that it could be an assessment of change in therapeutic clinical trials. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that quantitative WB-MSK-MRI findings associate with FSHD1 severity measured using established functional assessments.

Reachable workspace analysis is a potential measurement for impairment of the upper extremity in neuralgic amyotrophy.

INTRODUCTION/AIMS: Neuralgic amyotrophy (NA) is a multifocal neuropathy involving the nerves of the upper extremity, limiting functional capability and reducing range of motion. The reachable workspace (RWS) is a computerized three-dimensinal analysis system that evaluates the relative surface area (RSA) of an individual's arm reachability and has shown utility in several neuromuscular disorders. The aims of this study were to examine the ability of the RWS to quantitatively detect limitations in upper extremity active range of motion in patients with NA, and correlate these with other upper extremity functional outcome measures. METHODS: Forty-seven patients with NA and 25 healthy age- and sex-matched controls were measured with the RWS. Study participants' RSAs were correlated with scores on the Shoulder Rating Questionnaire (SRQ), the Disabilities of Arm Shoulder and Hand (DASH) questionnaire, and upper extremity strength measurements using hand-held dynamometry. RESULTS: Patients with NA showed significantly lower values in the affected arm for all quadrants (except for the ipsilateral lower quadrant) and total RSA compared with controls (P < 0.001). We found moderate correlations between the reachable workspace, the DASH questionnaire result (r = -0.415), and serratus anterior muscle strength (r = 0.414). DISCUSSION: RWS is able to detect limitations in active range of motion of the affected arm in patients with NA, and is moderately correlated with upper extremity functional measures. RWS can demonstrate impairment of the affected upper extremity in NA and it has potential as a clinical outcome measure.

Effect of the Affordable Care Act on healthcare utilization for Veterans with spinal cord injuries and disorders.

Context/Objective: Provisions of the Affordable Care Act (ACA) potentially increase insurance options for Veterans with disabilities. We examined Veterans with spinal cord injuries and disorders (SCI/D) to assess whether the ACA was associated with changes in healthcare utilization from Department of Veterans Affairs (VA) healthcare facilities.Design: Using national VA data, we investigated impacts on VA healthcare utilization pre- (2012/13) and post-ACA (2014/15) implementation with negative binomial regression models.Setting: VA healthcare facilities.Participants: 8,591 VA users with SCI/D. Veterans with acute myelitis, Guillain-Barré syndrome, multiple sclerosis, or amyotrophic lateral sclerosis were excluded as were patients who died during the study period.Interventions: We assessed VA healthcare utilization before and after ACA implementation.Outcome Measures: Total numbers of VA visits for SCI/D care, diagnostic care, primary care, specialty care, and mental health care, and VA admissions.Results: The number of VA admissions was 7% higher in the post than pre-ACA implementation period (P < 0.01). The number of VA visits post-implementation increased for SCI/D care (8%; P < 0.01) and specialty care (12%; P < 0.001). Conversely, the number of mental health visits was 17% lower in the post-ACA period (P < 0.001). Veterans with SCI/D who live <5 miles from their nearest VA facility received VA care more frequently than those ≥40 miles from VA (P < 0.001).Conclusion: Counter to expectations, results suggest that Veterans with SCI/D sought more frequent VA care after ACA implementation, indicating Veterans with SCI/D continue to utilize the lifelong, comprehensive care provided at VA.

Characterization of Telehealth Use in Veterans With Spinal Cord Injuries and Disorders.

BACKGROUND: Individuals with spinal cord injuries and disorders (SCI/D) require frequent interdisciplinary health care to address impairments in mobility, autonomic function, and secondary complications. Telehealth has the capacity to substantially transform health care delivery and improve care by increasing access and communication. However, relatively little is known about telehealth use in this specific population. Here we attempt to fill part of this gap. OBJECTIVE: To investigate the frequency and characteristics associated with telehealth use in Veterans with SCI/D. DESIGN: Cross-sectional, descriptive project. SETTING: Veterans Health Administration (VHA) facilities. PARTICIPANTS: A total of 15 028 Veterans living with SCI/D who received services from the VHA SCI/D System of Care. INTERVENTION: Not applicable. OUTCOME MEASURES: Frequency and characteristics associated with VHA telehealth utilization. RESULTS: Of the 15 028 Veterans with SCI/D included in the evaluation, 17% used some form of telehealth in VHA Fiscal Year (FY)2017. Veterans older than 65 years of age had lower odds (odds ratio [OR] = 0.88, P < .05, confidence interval [CI] 0.80-0.98) of using telehealth. Being Caucasian (OR = 1.29, P < .01, CI 1.09-1.52), living in rural areas (OR = 1.16, P < .01, CI 1.05-1.28), living greater distances away from the VHA (P < .01 for all distances), and being in priority group 8, meaning that Veterans have higher copayment requirements (OR = 1.46, P < .001, CI 1.19-1.81), were all significantly associated with greater odds of telehealth use. The most frequent types of telehealth used were real-time clinical video and store-and-forward between a provider and patient within the same hub network. CONCLUSION: There are opportunities to increase telehealth adoption in the SCI/D arena. The findings from this project highlight which Veterans are currently using telehealth services, as well as gaps regarding telehealth adoption in this population.

Motion sensor-acquired reachable workspace correlates with patient-reported upper extremity activities of daily living (ADL) function in facioscapulohumeral dystrophy.

BACKGROUND: This study examines the correlation, and clinical meaningfulness, between reachable workspace outcome and reported activities of daily living (ADL) function of individuals with facioscapulohumeral dystrophy (FSHD). METHODS: Twenty-one FSHD subjects with various disease severity (clinical severity scores 1-4) underwent reachable workspace evaluation and completed the Quality of Life in Neurological Disorders (NeuroQoL) upper extremity questionnaire. Spearman and receiver operator curve analyses were performed. RESULTS: Moderate correlation was found between NeuroQoL scores and total (ρ = 0.7609; P < .01), and upper-quadrants relative surface areas (RSAs) (ρ = 0.6969; P < .01). Five specific items (ie, shirt on, shirt off, use spoon, pull on pants, pick-up clothes) demonstrated even higher correlations with total (ρ = 0.8397; P < .01) and above shoulder (ρ = 0.8082; P < .01) RSAs. A total RSA cuffoff value of 0.70 would achieve 100% sensitivity and 94% specificity (area under the curve = 0.975). CONCLUSIONS: Reachable workspace values identify when individuals have difficulties performing ADLs at home. This information improves patient monitoring, and clinical decision making by enabling more timely recommendations for medications, assistive devices, or considerations for clinical trial enrollments.

Longitudinal study of upper extremity reachable workspace in fascioscapulohumeral muscular dystrophy.

Facioscapulohumeral Dystrophy (FSHD) results in slowly progressive strength impairment, especially the upper extremities. Recent discoveries regarding pathophysiology have led to exciting novel therapeutic strategies. To further facilitate drug development, improved FSHD outcome measures that are functionally-relevant and sensitive to longitudinal change will be critical. Recently, a motion sensor (Kinect)-based upper extremity outcome called 'reachable workspace' that provides a quantitative reconstruction of an individual's reachability was developed. In this study, changes in reachable workspace were tracked upwards for five-years in 18 FSHD subjects. Results show -1.63 %/year decline in total reachable workspace (p = 0.144); with most notable decline in the above-the-shoulder level quadrants (upper-lateral Q3: -9.5 %/year, p < 0.001 and upper-medial Q1: -6.8 %/ year, p = 0.063) with no significant changes in the lower quadrants (Q2, Q4). Reachable workspace declined more significantly if the subjects were challenged with 500 g wrist weights: total reachable workspace: -1.82 %/year, p = 0.039; Q1: -7.20 %/year, p = 0.041; Q3: -8.09 %/year, p = 0.001. Importantly, reachable workspace outcome was also able to distinguish subgroups in FSHD: mildly- and severely-affected with essentially unchanging reachability over years, and moderately-affected who demonstrate the most detectable changes longitudinally. The study demonstrates utility for measuring declines in upper quadrant reachability, and provides enrichment/stratification of FSHD populations most likely to show treatment effects in clinical trials.

Evaluating the Use of Medicare Part D in the Veteran Population With Spinal Cord Injury/Disorder.

OBJECTIVE: To examine the different sources of medications, the most common drug classes filled, and the characteristics associated with Medicare Part D pharmacy use in veterans with spinal cord injury/disorder (SCI/D). DESIGN: Retrospective, cross-sectional, observational study. SETTING: Outpatient clinics and pharmacies. PARTICIPANTS: Veterans (N=13,442) with SCI/D using Medicare or Veteran Affairs pharmacy benefits. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Characteristics and top 10 most common drug classes were examined in veterans who (1) used VA pharmacies only; (2) used both VA and Medicare Part D pharmacies; or (3) used Part D pharmacies only. Chi-square tests and multinomial logistic regression analyses were used to determine associations between various patient variables and source of medications. Patient level frequencies were used to determine the most common drug classes. RESULTS: A total of 13,442 veterans with SCI/D were analyzed in this study: 11,788 (87.7%) used VA pharmacies only, 1281 (9.5%) used both VA and Part D pharmacies, and 373 (2.8%) used Part D pharmacies only. Veterans older than 50 years were more likely to use Part D pharmacies, whereas those with traumatic injury, or secondary conditions, were less associated with the use of Part D pharmacies. Opioids were the most frequently filled drug class across all groups. Other frequently used drug classes included skeletal muscle relaxants, gastric medications, antidepressants (other category), anticonvulsants, and antilipemics. CONCLUSIONS: Approximately 12% of veterans with SCI/D are receiving medication outside the VA system. Polypharmacy in this population of veterans is relatively high, emphasizing the importance of health information exchange between systems for improved care for this medically complex population.

Neuropathic pain and SCI: Identification and treatment strategies in the 21st century.

Pain is a common complication in patients following spinal cord injury (SCI), with studies citing up to 80% of patients reporting some form of pain. Neuropathic pain (NP) makes up a substantial percentage of all pain symptoms in patients with SCI and is often complex. Given the high prevalence of NP in patients with SCI, proper identification and treatment is imperative. Indeed, identification of pain subtypes is a vital step toward determining appropriate treatment. A variety of pharmacological and non-pharmacological treatments can be undertaken including antiepileptics, tricyclic antidepressants, opioids, transcranial direct current stimulation, and invasive surgical procedures. Despite all the available treatment options and advances in the field of SCI medicine, providing adequate treatment of NP after SCI continues to be challenging. It is therefore extremely important for clinicians to have a strong foundation in the identification of SCI NP, as well as an understanding of appropriate treatment options. Here, we highlight the definitions and classification tools available for NP identification, and discuss current treatment options. We hope that this will not only provide a better understanding of NP for physicians in various subspecialties, but that it will also help guide future research on this subject.

Demystifying Poststroke Pain: From Etiology to Treatment.

Pain after stroke is commonly reported but often incompletely managed, which prevents optimal recovery. This situation occurs in part because of the esoteric nature of poststroke pain and its limited presence in current discussions of stroke management. The major specific afflictions that affect patients with stroke who experience pain include central poststroke pain, complex regional pain syndrome, and pain associated with spasticity and shoulder subluxation. Each disorder carries its own intricacies that require specific approaches to treatment and understanding. This review aims to present and clarify the major pain syndromes that affect patients who have experienced a stroke in order to aid in their diagnosis and treatment.

Characterization of ectopic colonies that form in widespread areas of the nervous system with neural stem cell transplants into the site of a severe spinal cord injury.

We reported previously the formation of ectopic colonies in widespread areas of the nervous system after transplantation of fetal neural stem cells (NSCs) into spinal cord transection sites. Here, we characterize the incidence, distribution, and cellular composition of the colonies. NSCs harvested from E14 spinal cords from rats that express GFP were treated with a growth factor cocktail and grafted into the site of a complete spinal cord transection. Two months after transplant, spinal cord and brain tissue were analyzed histologically. Ectopic colonies were found at long distances from the transplant in the central canal of the spinal cord, the surface of the brainstem and spinal cord, and in the fourth ventricle. Colonies were present in 50% of the rats, and most rats had multiple colonies. Axons extended from the colonies into the host CNS. Colonies were strongly positive for nestin, a marker for neural precursors, and contained NeuN-positive cells with processes resembling dendrites, GFAP-positive astrocytes, APC/CC1-positive oligodendrocytes, and Ki-67-positive cells, indicating ongoing proliferation. Stereological analyses revealed an estimated 21,818 cells in a colony in the fourth ventricle, of which 1005 (5%) were Ki-67 positive. Immunostaining for synaptic markers (synaptophysin and VGluT-1) revealed large numbers of synaptophysin-positive puncta within the colonies but fewer VGluT-1 puncta. Continuing expansion of NSC-derived cell masses in confined spaces in the spinal cord and brain could produce symptoms attributable to compression of nearby tissue. It remains to be determined whether other cell types with self-renewing potential can also form colonies.

Central Neuropathic Pain in Spinal Cord Injury.

Spinal cord injury (SCI) is a devastating medical condition affecting 1.2 million people in the United States. Central neuropathic pain is one of the most common medical complications of SCI. Current treatment options include opioids, antiepileptic agents such as gabapentin, antispastic agents such as baclofen or tizanidine, and tricyclic acid. Other options include complementary, nonpharmacological treatment such as exercise or acupuncture, interventional treatments, and psychological approaches. Although these treatment options exist, central neuropathic pain in patients with SCI is still extremely difficult to treat because of its complexity. To develop and provide more effective treatment options to these patients, proper assessment of and classification tools for central neuropathic pain, as well as a better understanding of the pathophysiology, are needed. A combination of approaches, from standard general pain assessments to medically specific questions unique to SCI pathophysiology, is essential for this population. A multidisciplinary approach to patient care, in addition with a better understanding of pathophysiology and diagnosis, will lead to improved management and treatment of patients with SCI displaying central neuropathic pain. Here we summarize the most recent classification tools, pathophysiology, and current treatment options for patients with SCI with central neuropathic pain.

IFN-γ-induced apoptosis of human embryonic stem cell derived oligodendrocyte progenitor cells is restricted by CXCR2 signaling.

Engraftment of human embryonic stem cell (hESC)-derived OPCs in animal models of demyelination results in remyelination and clinical recovery, supporting the feasibility of cell replacement therapies in promoting repair of damaged neural tissue. A critical gap in our understanding of the mechanisms associated with repair revolves around the effects of the local microenvironment on transplanted cell survival. We have determined that treatment of human ESC-derived OPCs with the pleiotropic cytokine IFN-γ promotes apoptosis that is associated with mitochondrial cytochrome c released into the cytosol with subsequent caspase 3 activation. IFN-γ-induced apoptosis is mediated, in part, by secretion of the CXC chemokine ligand 10 (CXCL10) from IFN-γ-treated cells. Signaling through the chemokine receptor CXCR2 by the ligand CXCL1 functions in a tonic manner by muting apoptosis and this is associated with reduced levels of cytosolic cytochrome c and impaired cleavage of caspase 3. These findings support a role for both IFN-γ and CXCL10 in contributing to neuropathology by promoting OPC apoptosis. In addition, these data suggest that hOPCs used for therapeutic treatment for human neurologic disease/damage are susceptible to death through exposure to local inflammatory cytokines present within the inflammatory milieu.

Derivation of oligodendrocyte progenitor cells from human embryonic stem cells.

The directed differentiation of human pluripotent stem cells into specific, determined, and high-purity cell types can provide a means to study the cellular and molecular mechanisms of development and to generate cells for potential therapeutic applications. The ability to derive homogeneous cell populations obviates the need for transgene expression or cell sorting methods and can improve selection efficiency, lineage differentiation, cell viability, and clinical utility. Compared to undifferentiated pluripotent stem cells, high-purity cell phenotypes for clinical therapeutic strategies are expected to enhance engraftment, potentiate clinical efficacy, and decrease the risk of adverse effects such as dedifferentiation or teratoma formation. Clinical interest in the derivation of oligodendrocyte progenitor cells from pluripotent stem cells is based on research that demonstrates the effectiveness of progenitor cell transplants to improve outcomes after spinal cord injury. Here, we describe a protocol to generate oligodendroglial lineage-specific cells in high purity from human embryonic stem cells.

Endogenous remyelination is induced by transplant rejection in a viral model of multiple sclerosis.

Human embryonic stem cell-derived oligodendrocyte progenitors (OPCs) were transplanted into mice persistently infected with the neurotropic JHM strain of mouse hepatitis virus with established demyelination. Engrafted cells did not survive past 2 weeks following transplantation despite treatment with high dose cyclosporine A. While T cell infiltration into the CNS was dampened, elevated numbers of macrophage/microglia and endogenous OPCs were evident surrounding the implantation site and this was associated with increased remyelination. These data suggest that remyelination was initiated by the local response to xenograft transplantation. These findings illustrate the complexities of OPC transplantation into areas of robust immune-mediated pathology.

Derivation of high-purity oligodendroglial progenitors.

Oligodendrocytes are a type of glial cells that play a critical role in supporting the central nervous system (CNS), in particular insulating axons within the CNS by wrapping them with a myelin sheath, thereby enabling saltatory conduction. They are lost, and myelin damaged - demyelination - in a wide variety of neurological disorders. Replacing depleted cell types within demyelinated areas, however, has been shown experimentally to achieve remyelination and so help restore function. One method to produce oligodendrocytes for cellular replacement therapies is through the use of progenitor or stem cells. The ability to differentiate progenitor or stem cells into high-purity fates not only permits the generation of specific cells for transplantation therapies, but also provides powerful tools for studying cellular mechanisms of development. This chapter outlines methods of generating high-purity OPCs from multipotent neonatal progenitor or human embryonic stem cells.