Evaluation of clinical outcomes and employment status in veterans with dual diagnosis of traumatic brain injury and spinal cord injury.

PURPOSE: To examine clinical outcomes and employment status in Veterans with and without a dual diagnosis of traumatic brain injury (TBI) and spinal cord injury (SCI). METHODS: This cross-sectional study examined a national sample of Veterans enrolled in the VA Million Veteran Program who completed the Comprehensive TBI Evaluation (CTBIE) as part of the Veterans Health Administration's TBI Screening and Evaluation Program. Veterans (N = 12,985) were classified into the following TBI/SCI groups using CTBIE data: those with a dual diagnosis of TBI and SCI (TBI+/SCI+); those with a history of TBI but no SCI (TBI+/SCI-); and those with no history of TBI or SCI (TBI-/SCI-; i.e., the control group). CTBIE-derived outcomes included neurobehavioral symptoms, comorbid psychiatric symptoms, pain and pain interference, and employment status. RESULTS: Chi-square analyses showed significant associations between TBI/SCI group and all clinical outcomes evaluated (all p's < .001; V = 0.07-0.11). In general, the TBI+/SCI+ and TBI +/SCI- groups endorsed comparable levels of neurobehavioral symptoms, psychiatric symptoms, and pain, but significantly greater rates of symptoms and pain relative to the TBI-/SCI- group. Effect sizes for all pairwise comparisons were small (φ = 0.01-0.11). Finally, there was no significant association between TBI/SCI group and employment status (p = .170; V = 0.02), with all three groups showing relatively comparable rates of unemployment. CONCLUSIONS: Regardless of SCI status, Veterans with TBI history endorsed poorer clinical outcomes than Veterans without TBI and SCI. However, rates of unemployment were similarly high across all three groups. Findings suggest that any Veteran completing the CTBIE may be at risk for poor clinical and employment outcomes.

Difficulty Obtaining Daily Necessities and Difficulty Obtaining SCI Services During the COVID-19 Pandemic Among People With Spinal Cord Injury.

OBJECTIVE: To describe the self-reported difficulties during the COVID-19 pandemic on the lives of persons with traumatic spinal cord injury (SCI), and to identify the factors measured prior the pandemic that predict the number of difficulties obtaining daily necessities and difficulties obtaining SCI services during the pandemic. DESIGN: Cohort study. SETTING: A state SCI outcomes follow-up database in the southeastern United States. PARTICIPANTS: 297 participants (N=297) met the following eligibility criteria: (1) ≥18 years of age, (2) traumatic SCI, (3) minimum of 1-year post-injury, and (4) having completed a longitudinal study questionnaire immediately prior to the pandemic (between 12/1/2019 and 03/11/2020). INTERVENTIONS: N/A. MAIN OUTCOME MEASURE(S): The outcome measures were the self-reported number of difficulties obtaining daily necessities (difficulties to get food, medication, and routine medical/dental care) and difficulties obtaining SCI services during the pandemic (difficulties to get treatment for SCI-related problems, to maintain regular SCI equipment, and to get SCI supplies). RESULTS: Among 297 eligible participants, 247 (83%) have completed the follow-up during the pandemic between December 2020 and December 2021. There were 22% participants having at least 1 difficulty obtaining daily necessities and 19% participants having at least 1 difficulty obtaining SCI services. Younger, ambulatory participants, cervical 1-4 injury level, lower household income, more health conditions, and no routine health care access prior to the pandemic were associated with greater number of difficulties obtaining daily necessities. Women, non-ambulatory participants, marital relation, having need for physical assistance, more health conditions, and no routine health care access prior to the pandemic related to greater number of difficulties obtaining SCI services. CONCLUSIONS: People with SCI have experienced living difficulties during the COVID-19 pandemic. Of particular importance, no routine health care access and more health conditions are related to more difficulties obtaining both daily necessities and SCI services after controlling the socio-demographics and injury characteristics.

Relationships of Self-reported Opioid Use and Misuse and Pain Severity With Probable Major Depression Among Participants With Spinal Cord Injury.

OBJECTIVES: To examine the relations of pain intensity, opioid use, and opioid misuse with depressive symptom severity and probable major depression (PMD) among participants with spinal cord injuries (SCI), controlling for demographic, injury, and socioeconomic characteristics. STUDY DESIGN: Cohort study. SETTING: Medical University in the Southeastern United States (US). PARTICIPANTS: Participants (N=918) were identified from 1 of 2 sources including a specialty hospital and a state-based surveillance system in the Southeastern US. Participants were a minimum of 18 years old at enrollment and had SCI with non-complete recovery. Participants were on average 57.5 years old at the time of the study and an average of 24.4 years post SCI onset. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Participants completed a self-report assessment that included frequency of prescription opioid use and misuse, based on the National Survey on Drug Use and Health (NSDUH), and the PHQ - 9 to measure depressive symptom severity and PMD. RESULTS: Opioid use, opioid misuse, and pain intensity were related to elevated depressive symptom severity and higher odds of PMD. Non-Hispanic Blacks had fewer depressive symptoms and lower odds of PMD, as did those with higher incomes. Veterans had lower risk of PMD, whereas ambulatory participants had a higher risk of PMD. Age at SCI onset had a mixed pattern of significance, whereas years of education and years since injury were not significant. CONCLUSIONS: The relation between pain intensity with depressive symptom severity and PMD was profound, consistent with the biopsychosocial model of pain. The greater risk of PMD and higher depressive symptom severity among those using opioids and misusing opioids raises further concern about long-term prescription opioid use. Alternative treatments are needed.

Australian arm of the International Spinal Cord Injury (Aus-InSCI) community survey: 1. population-based design, methodology and cohort profile.

STUDY DESIGN: Cross-sectional survey. OBJECTIVES: To describe design and methods of Australian arm of International Spinal Cord Injury (Aus-InSCI) community survey, reporting on participation rates, potential non-response bias and cohort characteristics. SETTING: Survey of community-dwelling people with SCI at least 12 months post-injury, recruited between March 2018 and January 2019, from state-wide SCI services, a government insurance agency and not-for-profit consumer organisations across four Australian states. METHODS: The Aus-InSCI survey combined data for people with SCI from nine custodians, using secure data-linkage processes, to create a population-based, anonymised dataset. The Aus-InSCI questionnaire comprised 193 questions. Eligibility, response status and participation rates were calculated. Descriptive statistics depict participant characteristics. Logistic regression models were developed for probability of participation, and inverse probability weights generated to assess potential non-response bias. RESULTS: 1579 adults with SCI were recruited, a cooperation rate of 29.4%. Participants were predominantly male (73%), with 50% married. Mean age was 57 years (range 19-94) and average time post-injury 17 years (range 1-73). Paraplegia (61%) and incomplete lesions (68%) were most common. Males were more likely than females to have traumatic injuries (p < 0.0001) and complete lesions (p = 0.0002), and younger age-groups were more likely to have traumatic injuries and tetraplegia (p < 0.0001). Potential non-response bias evaluated using selected outcomes was found to be negligible in the Aus-InSCI cohort. CONCLUSIONS: The Aus-InSCI survey made efforts to maximise coverage, avoid recruitment bias and address non-response bias. The distributed, linked and coded (re-identifiable at each custodian level) 'virtual quasi-registry' data model supports systematic cross-sectional and longitudinal research.

Life Satisfaction in Individuals With Long-Term Traumatic Spinal Cord Injury: An Investigation of Associated Biopsychosocial Factors.

OBJECTIVE: To investigate relationships between self-reported biological, psychological, and social factors and global, vocational, and home life satisfaction in individuals with traumatic spinal cord injury (SCI) an average of more than 30 years postinjury. DESIGN: Cross-sectional analyses of self-report assessment data. SETTING: Specialty and university hospitals in the southeastern and midwestern United States. PARTICIPANTS: Individuals with a history of traumatic SCI (n=546) who responded to the most recent data collection period of the SCI Longitudinal Aging Study (2018-2019) and who were at least 2 years postinjury and at least 18 years or older at initial study enrollment. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Global life satisfaction, home life satisfaction, and vocational life satisfaction as measured by the Life Situation Questionnaire-Revised. RESULTS: Taken together, the biopsychosocial variables explained 55.1% of the variance in global life satisfaction. Less severe depressive symptoms, greater emotional social support, and greater instrumental social support were significantly associated with greater global life satisfaction. Together, the independent variables explained 50.7% of the variance in home life satisfaction. Being in a relationship, having less severe depressive symptoms, having greater emotional social support, and having greater instrumental social support were significantly associated with home life satisfaction. Together, the independent variables explained 44.8% of the variance in vocational satisfaction. Being White, non-Hispanic, having more years of education, being in a relationship, having less severe depressive symptoms, and having greater emotional social support were significantly associated with greater vocational satisfaction. CONCLUSION: These results support the need to assess psychological symptoms and available social support as potential modifiable factors related to several domains of life satisfaction in this aging population. Improving psychological symptoms and strengthening available social support may relate to improved life satisfaction.

Mediating Effects of Pain Interference on the Relationships Between Pain Intensity and Probable Major Depression Among Participants With Spinal Cord Injury.

OBJECTIVE: To evaluate whether pain interference mediates the relationship between pain intensity and probable major depression (PMD) among persons with spinal cord injury (SCI), accounting for differences in the frequency of prescription medication use and resilience. DESIGN: Cross-sectional analysis using self-report assessment. SETTING: Medical university in the Southeastern United States. PARTICIPANTS: There were a total of 4670 participants (N=4670), all of whom had traumatic SCI of at least 1-year duration, identified from the Southeastern Regional SCI Model System and 2 state-based surveillance systems. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The Patient Health Questionnaire-9 was used to define PMD. Covariates included demographic and injury characteristics, pain severity, pain interference, and resilience. Separate sets of multistage logistic regression analyses were conducted for 3 levels of prescription pain medication use (daily, occasional/weekly, none). RESULTS: Pain intensity was related to a greater risk of PMD (odds ratio [OR]daily pain medication user, 1.28; 95% confidence interval [CI], 1.21-1.35; ORoccasional/weekly pain medication user, 1.26; 95% CI, 1.16-1.36; ORnonpain medication user, 1.44; 95% CI, 1.33-1.56), but this relationship disappeared after consideration of pain interference (ORdaily pain medication user, 0.97; 95% CI, 0.90-1.04; ORoccasional/weekly pain medication user, 0.94; 95% CI, 0.84-1.05; ORnonpain medication user, 1.07; 95% CI, 0.95-1.20), which indicates pain interference was a mediator between pain intensity and PMD and there was no direct relationship between pain intensity and PMD. Resilience was protective of PMD in each model but was not a mediator. CONCLUSIONS: Although pain intensity was associated with PMD, the relationship was mediated by pain interference. Resilience was an important protective factor. Therefore, clinicians should assess pain interference when screening for PMD and direct treatment at reducing pain interference. Building resilience may further reduce the risk of PMD.

Neuropsychological Performance and Functional Capacity Following Mild Traumatic Brain Injury in Veterans.

OBJECTIVE: To examine the relationship between neuropsychological functioning and performance-based functional capacity in veterans with a history of mild traumatic brain injury (mTBI), as well as the moderating effects of age and psychiatric symptoms on this relationship. SETTING: Three Veterans Affairs medical centers. PARTICIPANTS: One hundred nineteen Iraq/Afghanistan veterans with a history of mTBI and self-reported cognitive difficulties. DESIGN: Cross-sectional, secondary data analysis of baseline measures in a randomized controlled trial. MAIN MEASURES: The main outcome measure, functional capacity, was assessed using the objective and performance-based University of California San Diego Performance-based Skills Assessment-Brief. A global deficit score (GDS) was created as a composite score for performance on a battery of neuropsychological measures assessing domains of attention, processing speed, executive functioning, and verbal memory performance. Posttraumatic stress disorder (PTSD) symptom severity was assessed using the PTSD Checklist-Military Version, and depressive symptom severity was assessed using the Beck Depression Inventory, Second Edition. RESULTS: Bivariate analyses indicated that worse neuropsychological performance (ie, higher GDS) and greater PTSD symptom severity were associated with worse communication abilities and worse overall functional capacity. Multiple linear regressions demonstrated that GDS and PTSD symptom severity explained 9% of the variance in communication and 10% of the variance in overall functional capacity; however, GDS emerged as the only significant predictor in both regressions. Age, PTSD, and depressive symptom severity did not moderate the relationship between GDS and overall functional capacity. Performance in the verbal learning and memory domain emerged as the strongest neuropsychological predictor of communication and overall functional capacity. CONCLUSIONS: Worse neuropsychological functioning was moderately associated with worse performance-based functional capacity, even when accounting for PTSD symptom severity. Verbal learning and memory was the primary neuropsychological domain driving the relationship with functional capacity; improvement in verbal learning and memory may translate into improved functional capacity.

Utilising International Statistical Classification of Diseases and Related Health Conditions (ICD)-10 Australian Modification Classifications of "Health Conditions" to Achieve Population Health Surveillance in an Australian Spinal Cord Injury Cohort.

STUDY DESIGN: Retrospective, non-randomised, registry controlled. OBJECTIVE: To develop a conceptual ICD-10 taxonomic framework for population health surveillance across all-phases of spinal cord injury and disorders (SCI/D). SETTING: Public Hospital Admitted Patient Care (APC) collection, South Australian Dept. Health, South Australia, Australia. METHODS: A core ICD-10-Australian Modification (AM) coded dataset was retrieved from the APC hospital patient admission collection (2012-2017). Search filters and key words referenced to the National Library of Medicine thesaurus identified and quantified incident SCI/D cases. Incident SCI/D case data held in the Australian Spinal Cord Injury Registry (ASCIR) of South Australia (2012-2017) tested fidelity. Data linkage to the South Australian Death Registry controlled for cohort attrition. Both unadjusted and case-mix adjusted core data set yields were evaluated. Outcomes were assessed in terms of APC frequency difference (Δ%) versus ASCIR. RESULTS: 3,504 APC cases were extracted, of which 504 (mean, SD age 55 ± 20 yrs; 348 [69%] male, 202 [39%] traumatic; 135 [32%]) cervical; 51 [10.1%] thoracic and (16 [3.2%]) lumbar met criteria. Comparator data were 385 ASCIR new index cases mean, SD age 56 ± 19 yrs, 229 [75%] male, 162 [42%] traumatic. Case-mix adjusted analysis yielded 336 (APC Δ33%) all-cause incident cases (vs. ASCIR -13 Δ%) and 131 incident cases of traumatic aetiologies (vs. ASCIR -19 Δ%). CONCLUSIONS: The ICD-10 core "Health Condition" data-set assembled extends our understanding of SCI/D epidemiology and with further development may create a cost-efficient and sustainable framework that will improve health system performance and equity within and between countries. SPONSORSHIP: The Lifetime Support Authority of South Australia sponsored the study.

Australian arm of the International Spinal Cord Injury (Aus-InSCI) Community Survey: 2. Understanding the lived experience in people with spinal cord injury.

STUDY DESIGN: Cross-sectional survey. OBJECTIVES: To identify common problems across key domains of functioning, health and wellbeing, as well as evaluate self-reported quality of life (QoL) by people with SCI, examining differences by age, gender, injury characteristics and level of mobility. SETTING: Data from four state-wide SCI clinical services, one government insurance agency and three not-for-profit consumer organisations. METHODS: Participants were 18 years or over with SCI and at least 12 months post-injury, recruited between Mar'18 and Jan'19. The Aus-InSCI questionnaire comprised 193 questions, including socio-demographics, SCI characteristics, body functions and structures, activities and participation, environmental and personal factors, and appraisal of health and well-being. General linear model was used to examine differences in functioning and QoL. RESULTS: Participants (mean age 57 years, range 19-94 years) with tetraplegia and/or complete injuries had more health problems, activity/participation problems and environmental barriers. However, self-rated overall QoL did not differ for injury level or completeness. Participants with more recent injuries exhibited lower independence levels, more mental health problems and poorer satisfaction with self and their living conditions. Major activity/participation problems related to intimate relationships and accessing public transportation. Less than half of the working age population were engaged in paid work. The top two environmental barriers frequently related to accessing public places or homes and unfavourable climatic conditions. CONCLUSIONS: This large, comprehensive community survey draws a detailed picture of the lived experience of people with SCI in Australia, identifying priority needs, gaps in services and barriers to achieving a full and satisfying life.

Relationships between the Bone Expression of Alzheimer's Disease-Related Genes, Bone Remodelling Genes and Cortical Bone Structure in Neck of Femur Fracture.

Neck of femur (NOF) fracture is a prevalent fracture type amongst the ageing and osteoporotic populations, commonly requiring total hip replacement (THR) surgery. Increased fracture risk has also been associated with Alzheimer's disease (AD) in the aged. Here, we sought to identify possible relationships between the pathologies of osteoporosis and dementia by analysing bone expression of neurotropic or dementia-related genes in patients undergoing THR surgery for NOF fracture. Femoral bone samples from 66 NOF patients were examined for expression of the neurotropic genes amyloid precursor protein (APP), APP-like protein-2 (APLP2), Beta-Secretase Cleaving Enzyme-1 (BACE1) and nerve growth factor (NGF). Relationships were examined between the expression of these and of bone regulatory genes, systemic factors and bone structural parameters ascertained from plain radiographs. We found strong relative levels of expression and positive correlations between APP, APLP2, BACE1 and NGF levels in NOF bone. Significant correlations were found between APP, APLP2, BACE1 mRNA levels and bone remodelling genes TRAP, RANKL, and the RANKL:OPG mRNA ratio, indicative of potential functional relationships at the time of fracture. Analysis of the whole cohort, as well as non-dementia (n = 53) and dementia (n = 13) subgroups, revealed structural relationships between APP and APLP2 mRNA expression and lateral femoral cortical thickness. These findings suggest that osteoporosis and AD may share common molecular pathways of disease progression, perhaps explaining the common risk factors associated with these diseases. The observation of a potential pathologic role for AD-related genes in bone may also provide alternative treatment strategies for osteoporosis and fracture prevention.

Biodegradable and biocompatible graphene-based scaffolds for functional neural tissue engineering: A strategy approach using dental pulp stem cells and biomaterials.

Neural tissue engineering aims to restore the function of nervous system tissues using biocompatible cell-seeded scaffolds. Graphene-based scaffolds combined with stem cells deserve special attention to enhance tissue regeneration in a controlled manner. However, it is believed that minor changes in scaffold biomaterial composition, internal porous structure, and physicochemical properties can impact cellular growth and adhesion. The current work aims to investigate in vitro biological effects of three-dimensional (3D) graphene oxide (GO)/sodium alginate (GOSA) and reduced GOSA (RGOSA) scaffolds on dental pulp stem cells (DPSCs) in terms of cell viability and cytotoxicity. Herein, the effects of the 3D scaffolds, coating conditions, and serum supplementation on DPSCs functions are explored extensively. Biodegradation analysis revealed that the addition of GO enhanced the degradation rate of composite scaffolds. Compared to the 2D surface, the cell viability of 3D scaffolds was higher (p < 0.0001), highlighting the optimal initial cell adhesion to the scaffold surface and cell migration through pores. Moreover, the cytotoxicity study indicated that the incorporation of graphene supported higher DPSCs viability. It is also shown that when the mean pore size of the scaffold increases, DPSCs activity decreases. In terms of coating conditions, poly- l-lysine was the most robust coating reagent that improved cell-scaffold adherence and DPSCs metabolism activity. The cytotoxicity of GO-based scaffolds showed that DPSCs can be seeded in serum-free media without cytotoxic effects. This is critical for human translation as cellular transplants are typically serum-free. These findings suggest that proposed 3D GO-based scaffolds have favorable effects on the biological responses of DPSCs.

Twenty-Five-Year Cross-sequential Analysis of Self-reported Problems: Findings From 5 Cohorts From the Spinal Cord Injury Longitudinal Aging Study.

OBJECTIVE: To evaluate how self-reported problems change over time among people with spinal cord injury (SCI). DESIGN: Cross-sequential analysis. SETTING: Medical university in the Southeastern United States. PARTICIPANTS: Participants included 1997 individuals with traumatic SCI of at least 1-year duration who were identified from participation in the SCI Longitudinal Aging Study from 1993-2018. INTERVENTIONS: None. MAIN OUTCOME MEASURES: The outcomes analyzed were 6 problem factors defined as health, social isolation, emotional distress, environmental barriers, money, and lack of opportunities. A series of cross-sequential models, using PROC MIXED procedure, were developed to evaluate the initial and change of the 6 problem factors over the 6 times of measurements in 25 years. RESULTS: Years post injury was negatively associated with initial status of problems of social isolation, emotional distress, environmental barriers, and lack of opportunities because participants with more years post injury at baseline reported lower scores on each factor. Longitudinally, with increased years post injury, higher scores were observed on the health problem factor. However, problems of social isolation, emotional distress, environmental barriers, money, and lack of opportunities decreased over time with increasing years post injury. CONCLUSIONS: Participants had more health problems with increasing years after SCI, but fewer problems of social isolation, emotional distress, environmental barriers, money, and lack of opportunities.

Predictors of Intervention Adherence in Compensatory Cognitive Training for Veterans With a History of Mild Traumatic Brain Injury.

OBJECTIVE: The purpose of this study was to determine modifiable predictors of intervention adherence in a study of group-based Compensatory Cognitive Training (CCT) for Iraq/Afghanistan War veterans with a history of mild traumatic brain injury (mTBI). METHODS: One hundred twenty-three veterans enrolled in a randomized controlled trial of a 10-week CCT intervention (54 assigned to CCT) and were evaluated at baseline, 5 weeks, 10 weeks, and 15 weeks. CCT adherence was determined by the number of CCT sessions attended, with more sessions indicative of greater adherence. Baseline demographic and clinical characteristics, and subjective and objective neuropsychological performance, were examined in relation to CCT session attendance. RESULTS: Older age and worse attention performance at baseline were associated with higher CCT attendance rates. CONCLUSIONS: This study generates preliminary evidence for potential modifiable neuropsychological factors that may improve engagement in CCT interventions.

Aspects of Executive Dysfunction and Racial/Ethnic Minority Status Are Associated With Unemployment Duration in Veterans With a History of Mild-to-Moderate Traumatic Brain Injury.

OBJECTIVE: To examine demographic, psychiatric symptom, and neuropsychological performance factors associated with duration of unemployment in Iraq/Afghanistan Veterans with a history of mild-to-moderate traumatic brain injury (TBI). DESIGN: Cross-sectional, secondary data analysis of baseline measures in a supported employment study. SETTING: VA medical center. PARTICIPANTS: Participants (N=50) were veterans with a history of mild-to-moderate TBI who were unemployed, stating a goal of returning to work, and had documented impairment in at least 1 neuropsychological domain. Participants were referred from VA vocational and assessment-based clinics. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Duration of unemployment, neuropsychological, and psychiatric symptom assessments. RESULTS: Bivariate correlations revealed that longer duration of unemployment was associated with greater posttraumatic stress disorder (P<.10) and depressive (P<.05) symptom severity, worse executive functioning (P<.05), and racial/ethnic minority status (P<.05). A multiple linear regression analysis including these independent variables explained 26.5% of the variance in duration of unemployment. Worse executive functioning, specifically reasoning and set-shifting, and minority status were each associated with longer duration of unemployment in the context of multiple independent variables. CONCLUSIONS: Our results underscore the importance of objective assessment of cognitive functioning in job-seeking Veterans with TBI histories. It may be useful to target aspects of executive functioning in vocational rehabilitation interventions and to provide additional assistance to Veterans from racial/ethnic minority groups.

Trends in nonroutine physician visits and hospitalizations: findings among five cohorts from the Spinal Cord Injury Longitudinal Aging Study.

STUDY DESIGN: Longitudinal cohort study OBJECTIVE: To evaluate lifetime variation in healthcare utilization among individuals with a chronic spinal cord injury (SCI). SETTING: Medical university in the Southeastern United States (US). METHODS: Participants were identified from two Midwestern University hospitals and a specialty hospital in the Southeastern US and were enrolled in 1973-1974, 1984-1985, 1993-1994, and 2003-2004. Generalized linear mixed models were used to explore changes in nonroutine physician visits, hospitalizations, and days hospitalized within the 24 months prior to the study. RESULTS: Significant temporal linear spline change was found for nonroutine physician visits. The proportion of participants reporting ≥10 nonroutine physician visits in the 24 months prior to assessment kept relatively constant over the 30 years post injury (p value of trend: p = 0.605) and sharply increased afterwards (pknot = 30 years since injury = 0.016). The trajectory for hospitalization and days hospitalized followed a quadratic pattern (pyears post injury2 < 0.001) for all participants. The proportion of individuals who had at least one hospitalization and were hospitalized for more than 1 week significantly declined from the onset of SCI to 25-30 years post injury, then significantly increased thereafter. CONCLUSIONS: The natural course of changes in three indices of healthcare utilization was curve-linearly, rather than linearly related to years post injury. People with SCI tended to have significant changes in healthcare utilization after about 30 years injury.

Work and SCI: a pilot randomized controlled study of an online resource for job-seekers with spinal cord dysfunction.

STUDY DESIGN: A prospective, parallel randomized controlled trial (RCT). OBJECTIVES: To test the preliminary effects of an online resource targeted to job-seekers with spinal cord injury or disorder (SCI/D), and to determine the feasibility of proceeding to a full-scale RCT. SETTING: A community cohort in Australia. METHODS: Forty-eight adults (M = 42 years, SD = 10.95, 27 males) were randomized to receive 4-weeks access to the Work and SCI resource (n = 25) or to a wait-list control group (n = 23). The Work and SCI intervention involved six stand-alone learning modules which provided job-searching and career-planning information through text, videos, and interactive activities. Self-report measures were administered at baseline and after 4 weeks: Job Procurement Self-Efficacy Scale (JSES), Life Orientation Test-Revised (LOT-R), and Patient Health Questionnaire-9 (PHQ-9). RESULTS: Online usage data identified high uptake of the Work and SCI resource, although study attrition was problematic. Intention-to-treat analyses failed to reach statistical significance, whereas complete data revealed a significant interaction effect for optimism (LOT-R). CONCLUSION: Further research to develop and enhance Work and SCI is indicated. Remediable strategies to optimize recruitment and statistical power in a future definitive RCT are discussed. SPONSORSHIP: This project was funded by the auDA Foundation (project 16019).

PAd2-DalPhos Enables the Nickel-Catalyzed C-N Cross-Coupling of Primary Heteroarylamines and (Hetero)aryl Chlorides.

Base-metal catalysts capable of enabling the assembly of heteroatom-dense molecules by cross-coupling of primary heteroarylamines and (hetero)aryl chlorides, while sought-after given the ubiquity of unsymmetrical di(hetero)arylamino fragments in pharmacophores, are unknown. Herein, we disclose the new "double cage" bisphosphine PAd2-DalPhos (L2). The derived air-stable NiII pre-catalyst C2 functions well at low loadings in challenging test C-N cross-couplings with established substrates, and facilitates the first Ni-catalyzed C-N cross-couplings of primary five- or six-membered ring heteroarylamines and activated (hetero)aryl chlorides, with synthetically useful scope that is competitive with Pd catalysis.

Changes in psychotropic prescription medication use and their relationship with mortality among people with traumatic spinal cord injury.

STUDY DESIGN: Prospective cohort study. OBJECTIVE: To identify the relationship of frequency of prescription medication use to treat pain, spasticity, sleep, and depression/stress, and change in prescription medication use with risk of all-cause mortality. SETTING: This study was initiated at a specialty hospital in the Southeastern USA, with follow-up and data analysis at an academic medical center in the Southeastern United States. METHODS: Prospective data were collected in 1997-1998 (Time 1) and 2007-2009 (Time 2), with mortality determined as of 31 December 2014. The initial participant cohort was comprised of 1386 participants with traumatic SCI who were adults and a minimum of 1-year post-injury at enrollment in 1997-1998. Of these, 863 participated at follow-up and 861 were included in the current mortality analysis. RESULTS: The frequency of taking prescription medication increased over the 10-year timeframe, particularly for sleep and pain. Each type of prescription medication at Time 1 was associated with later mortality, and an increase in medication use over time was associated with a greater risk of mortality for three of the four conditions (all except spasticity). A decrease in the frequency of pain medication use over time was associated with a decreased risk of all-cause mortality. CONCLUSIONS: More frequent use of prescription medication to treat pain, sleep, and depression/stress is related to all-cause mortality, and increases in the use of medications to treat these conditions is associated with elevated risk of all-cause mortality.

Ni and Cu-catalyzed one pot synthesis of unsymmetrical 1,3-di(hetero)aryl-1H-indazoles from hydrazine, o-chloro (hetero)benzophenones, and (hetero)aryl bromides.

The nickel-catalyzed cyclization of in situ generated ortho-chlorobenzophenone hydrazone derivatives, to afford 3-(hetero)aryl-1H-indazoles, is documented for the first time. The product 1H-indazoles can be transformed subsequently in a one-pot procedure into 1,3-di(hetero)aryl-1H-indazoles via copper-catalyzed N-arylation with (hetero)aryl bromides.

Musculoskeletal Health in the Context of Spinal Cord Injury.

PURPOSE OF REVIEW: This review assembles recent understanding of the profound loss of muscle and bone in spinal cord injury (SCI). It is important to try to understand these changes, and the context in which they occur, because of their impact on the wellbeing of SC-injured individuals, and the urgent need for viable preventative therapies. RECENT FINDINGS: Recent research provides new understanding of the effects of age and systemic factors on the response of bone to loading, of relevance to attempts to provide load therapy for bone in SCI. The rapidly growing dataset describing the biochemical crosstalk between bone and muscle, and the cell and molecular biology of myokines signalling to bone and osteokines regulating muscle metabolism and mass, is reviewed. The ways in which this crosstalk may be altered in SCI is summarised. Therapeutic approaches to the catabolic changes in muscle and bone in SCI require a holistic understanding of their unique mechanical and biochemical context.