Molars to Medicine: A Focused Review on the Pre-Clinical Investigation and Treatment of Secondary Degeneration following Spinal Cord Injury Using Dental Stem Cells.

Spinal cord injury (SCI) can result in the permanent loss of mobility, sensation, and autonomic function. Secondary degeneration after SCI both initiates and propagates a hostile microenvironment that is resistant to natural repair mechanisms. Consequently, exogenous stem cells have been investigated as a potential therapy for repairing and recovering damaged cells after SCI and other CNS disorders. This focused review highlights the contributions of mesenchymal (MSCs) and dental stem cells (DSCs) in attenuating various secondary injury sequelae through paracrine and cell-to-cell communication mechanisms following SCI and other types of neurotrauma. These mechanistic events include vascular dysfunction, oxidative stress, excitotoxicity, apoptosis and cell loss, neuroinflammation, and structural deficits. The review of studies that directly compare MSC and DSC capabilities also reveals the superior capabilities of DSC in reducing the effects of secondary injury and promoting a favorable microenvironment conducive to repair and regeneration. This review concludes with a discussion of the current limitations and proposes improvements in the future assessment of stem cell therapy through the reporting of the effects of DSC viability and DSC efficacy in attenuating secondary damage after SCI.

The Translation of Nanomedicines in the Contexts of Spinal Cord Injury and Repair.

PURPOSE OF THIS REVIEW: Manipulating or re-engineering the damaged human spinal cord to achieve neuro-recovery is one of the foremost challenges of modern science. Addressing the restricted permission of neural cells and topographically organised neural tissue for self-renewal and spontaneous regeneration, respectively, is not straightforward, as exemplified by rare instances of translational success. This review assembles an understanding of advances in nanomedicine for spinal cord injury (SCI) and related clinical indications of relevance to attempts to design, engineer, and target nanotechnologies to multiple molecular networks. RECENT FINDINGS: Recent research provides a new understanding of the health benefits and regulatory landscape of nanomedicines based on a background of advances in mRNA-based nanocarrier vaccines and quantum dot-based optical imaging. In relation to spinal cord pathology, the extant literature details promising advances in nanoneuropharmacology and regenerative medicine that inform the present understanding of the nanoparticle (NP) biocompatibility-neurotoxicity relationship. In this review, the conceptual bases of nanotechnology and nanomaterial chemistry covering organic and inorganic particles of sizes generally less than 100 nm in diameter will be addressed. Regarding the centrally active nanotechnologies selected for this review, attention is paid to NP physico-chemistry, functionalisation, delivery, biocompatibility, biodistribution, toxicology, and key molecular targets and biological effects intrinsic to and beyond the spinal cord parenchyma. SUMMARY: The advance of nanotechnologies for the treatment of refractory spinal cord pathologies requires an in-depth understanding of neurobiological and topographical principles and a consideration of additional complexities involving the research's translational and regulatory landscapes.

A 5-year longitudinal structural equation model of social isolation and probable major depression among participants with spinal cord injury.

OBJECTIVE: To develop longitudinal structural models of social isolation and probable major depression (PMD) over a 5-year interval among participants with spinal cord injury (SCI). DESIGN: Longitudinal structural equation modeling of self-report assessments collected during two follow-ups (2013 as Time 1, 2018 as Time 2) of a 45-year multicohort longitudinal study. Participants (n = 557) were identified from a specialty hospital in the Southeastern United States and two Midwestern hospitals and were initially enrolled in 1973-1974, 1984-1985, 1993-1994, or 2003-2004. PMD symptomology was measured by the Patient Health Questionnaire-9 (PHQ-9) and was defined by PHQ-9 scores ≥ 10. Social isolation was represented by two latent dimensions: social disconnectedness, objective component measured by activities, and perceived isolation, based on subjective appraisals. Structural equation modeling assessed the relationship among social disconnectedness and perceived isolation measured at Time 1 and PMD measured at Times 1 and 2. RESULTS: Both social disconnectedness and perceived isolation, measured at Time 1, were significantly related with PMD measured at Time 1 (rSD_Time 1 and PMD_Time 1 = .49, p < .001; rPI_Time 1 and PMD_Time 1 = .66, p < .001) and Time 2 (rSD_Time 1 and PMD_Time 2 = .37, p < .001; rPI_Time 1 and PMD_Time 2 = .54, p < .001), indicating participants with greater perceived isolation and social disconnectedness were more likely to have greater likelihood of PMD, both cross-sectionally and longitudinally. Perceived isolation was more strongly related to PMD compared with social disconnectedness. CONCLUSION: Social isolation was associated with both current and future depression symptoms. People with more years post-SCI were less likely to have PMD. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

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.

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.

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.

Neuropsychological Correlates of PTSD and Depressive Symptom Improvement in Compensatory Cognitive Training for Veterans With a History of Mild Traumatic Brain Injury.

INTRODUCTION: Mild traumatic brain injury (mTBI), depression, and PTSD are highly prevalent in post-9/11 veterans. With the comorbidity of depression and PTSD in post-9/11 veterans with mTBI histories and their role in exacerbating cognitive and emotional dysfunction, interventions addressing cognitive and psychiatric functioning are critical. Compensatory Cognitive Training (CCT) is associated with improvements in prospective memory, attention, and executive functioning and has also yielded small-to-medium treatment effects on PTSD and depressive symptom severity. We sought to examine neuropsychological correlates of PTSD and depressive symptom improvement in veterans with a history of mTBI who received CCT. MATERIALS AND METHODS: Thirty-seven post-9/11 veterans with mTBI histories and cognitive complaints received 10 weekly 120-minute CCT group sessions. Participants completed a baseline neuropsychological assessment, including tests of premorbid functioning, attention/working memory, processing speed, verbal learning/memory, and executive functioning, and completed psychiatric symptom measures (PTSD and depression) at baseline, post-treatment, and a 5-week follow-up. Paired samples t-tests were used to examine statistically significant changes in PTSD (total and symptom cluster scores) and depressive symptom scores over time. Pearson's correlations were calculated between neuropsychological scores and PTSD and depressive symptom change scores at post-treatment and follow-up. Neuropsychological measures identified as significantly correlated with psychiatric symptom change scores were entered as independent variables in multivariable regression analyses to examine their association with symptom change at post-treatment and follow-up. RESULTS: Over 50% of CCT participants had clinically meaningful improvement in depressive symptoms (≥17.5% score reduction), and over 20% had clinically meaningful improvement in PTSD symptoms (≥10-point improvement) at post-treatment and follow-up. Examination of PTSD symptom cluster scores revealed a statistically significant improvement in avoidance/numbing at follow-up. Bivariate correlations indicated that worse baseline performance on Category Fluency was moderately associated with PTSD symptom improvement at post-treatment. Worse performance on both Category Fluency and Category Switching Accuracy was associated with improvement in depressive symptoms at post-treatment and follow-up. Worse performance on Trail-Making Number-Letter Switching was also associated with improvement in depressive symptoms at follow-up. Subsequent regression analyses revealed that worse processing speed and worse aspects of executive functioning at baseline were associated with depressive symptom improvement at post-treatment and follow-up. CONCLUSIONS: Worse baseline performances on tests of processing speed and aspects of executive functioning were significantly associated with improvements in PTSD and depressive symptoms during the trial. Our results suggest that cognitive training may bolster skills that are helpful for PTSD and depressive symptom reduction and that those with worse baseline functioning may benefit more from treatment because they have more room to improve.

Suicidal ideation among individuals aging with spinal cord injury.

OBJECTIVE: To identify the prevalence of suicidal ideation (SI) and its correlates among an aging cohort of people with spinal cord injury (SCI) with an average of more than three decades of having lived with SCI. RESEARCH METHOD: The study was a cross-sectional analysis of self-report assessment data. These data were collected from 2018 to 2019 during the most recent data collection period of the 45-year SCI Longitudinal Aging Study. Participants (n = 553) were identified from specialty and university hospitals in the southeastern and midwestern United States. The participants averaged 31 years since SCI onset, with an average age of 58 years. Participants were predominantly non-Hispanic, White (79%), male (70.1%), and had a cervical level SCI (51%). Approximately 23% of participants were ambulatory. SI was assessed using a nonzero response to the ninth item on the Patient Health Questionnaire-9. RESULTS: Over 14% of the sample endorsed experiencing recent SI. Bivariate analyses indicated that those with SI had greater pain severity, pain interference, depressive symptom severity, and frequency of anxiety. Having a cervical injury level, lower self-reported general health, instrumental social support, emotional social support, and fewer days spent outside the home were also associated with SI. Logistic regression analysis indicated that when all biopsychosocial variables were considered simultaneously, having a cervical-level injury and greater depressive symptom severity remained significantly associated with SI. CONCLUSION: The results of this study highlight the importance of continued assessment of depressive symptoms and SI as individuals age with SCI. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Pain interference and depressive symptom severity across 10 years in individuals with long-term spinal cord injury.

OBJECTIVE: To examine change in pain interference and depression over a 10-year time period in individuals with long-term traumatic spinal cord injury (SCI) and to identify the extent to which changes in pain interference over time predicts change in depressive symptoms. DESIGN: Longitudinal analyses of self-report assessment data. SETTING: Specialty and university hospitals in the Southeastern and Midwestern United States. PARTICIPANTS: Adults with a history of traumatic SCI (n = 504) who responded to the three most recent data collection periods of the SCI Longitudinal Aging Study (2008 [Time 1], 2013 [Time 2], and 2018 [Time 3]). The participants averaged 59 years of age and 32 years since injury onset at Time 3. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Patient Health Questionnaire (PHQ-9) assessed depressive symptom severity. The 7-item Pain Interference scale from the Brief Pain Inventory assessed pain interference. RESULTS: Over the three study timepoints, the sample averaged moderate levels of pain interference and mild depressive symptom severity. Unconditional linear growth models, reflecting changes in central tendency, indicated that pain interference significantly decreased and depressive symptom severity significantly increased over time. Multiple independent variables random coefficient modeling based on correlations suggested that change in pain interference was positively associated with change in depressive symptom severity over the 10-year study follow-up. CONCLUSION: Average depressive symptom severity worsened over time. Change in pain interference was positively associated with change in depressive symptom severity. These results point to the complexity of aging related changes in depressive symptoms and pain interference. They further support the need for continued assessment of mood and pain experiences, particularly among individuals reaching aging milestones with SCI.

Neuroanatomical Tract Tracers: Not Just for Neural Tracing Anymore.

Neuroanatomical tract tracers (NaTTs) have been used for neural circuit tracing for decades and now find recent applications in disease diagnosis and drug and gene delivery. In this Review, first the different subclasses of NaTTs including nonviral and viral types and their unique properties are discussed. The focus then is shifted to recent developments in improving the design and performance of NaTTs for neural circuit mapping, their role in disease diagnostics, and the emerging applications in drug and gene delivery targeted to the nervous system. In contrast to most molecular and biologic drugs that do not pass through the blood-brain barrier, NaTTs, including certain types of plant lectins, bacterial toxins, and some viruses, are readily taken up by nerve endings in mammalian muscle and efficiently transported within the central nervous system to the brain. Incorporating NaTTs into nanomedicines to bypass biological barriers and to deliver drugs to specific neurons thus presents an exciting direction and offers many possibilities for drug delivery. We hope that this Review will catalyze further discussions and collaborations among neuroscientists, biomedical researchers, and nanotechnologists that lead to innovative therapeutic options for treating neurological diseases.

Prehospital Cardiovascular Autoregulatory Disturbances Correlate With the Functional Neuroanatomy of Acute Spinal Cord Injury.

STUDY DESIGN: Retrospective study. OBJECTIVE: The importance of attenuating the cardiovascular autoregulatory disturbances accompanying acute spinal cord injury (SCI) has long been recognized. This report assembles SCI emergency service data and correlates cardiovascular parameters to preserved functional neuroanatomy. SUMMARY OF BACKGROUND DATA: The nascent nature of evidence-based reporting of prehospital cardiovascular autoregulatory disturbances in SCI indicates the need to assemble more information. MATERIALS AND METHODS: SCI data for <24 hours were extracted from ambulance and hospital records. The mean arterial pressure (MAP) was calculated. The International Standard for Neurological Classification of SCI (ISNCSCI) evaluates the primary outcome of motor incomplete injury (grades C/D) at acute presentation. Logistic regression was adjusted for multiple confounders that were expected to influence the odds of grade C/D. RESULTS: A cohort of 99 acute SCI cases was retained; mean (SD) age 40.7±20.5 years, 88 male, 84 tetraplegic, 65 grades A/B (motor complete injury), triage time 2±1.6 hours. The lowest recorded prehospital MAP [mean (SD): 77.9±19, range: 45-145 mm Hg] approached the nadir for adequate organ perfusion. Thirty-four (52%) grade A/B and 10 (30%) C/D cases had MAP readings <85 mm Hg. In data adjusted for age, injury level, and triage time a 5 mm Hg increase in the lowest MAP value was associated with a 34% increase in the odds of having motor incomplete injury at acute presentation (adjusted odds ratio=1.34; 95% CI: 1.11-1.61; P =0.002). CONCLUSION: An important observation with implications for timely and selective cardiovascular resuscitation during SCI prehospital care involves significant negative associations between the depth of systemic hypotension and preserved functional neuroanatomy. Regardless of the mechanism, our confounder-adjusted logistic regression model extends in-hospital evidence and provides a conceptual bedside-bench framework for future investigations.

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.

Memory, fluid reasoning, and functional capacity in adults experiencing homelessness.

BACKGROUND AND OBJECTIVE: In individuals experiencing homelessness, determinants of functional capacity (i.e. the ability to perform activities of daily living) are poorly understood. Identifying potentially modifiable correlates of functional capacity, such as cognitive abilities, may inform treatment targets to address independence and housing stability. This study aimed to identify the strongest neuropsychological predictors of variance in functional performance in 100 adults living in a homeless shelter. METHODS: Participants completed a brief cognitive screening test, from which four composite scores were derived, as well as tests of processing speed, fluid reasoning, premorbid intellectual function, and performance-based functional capacity. We conducted a hierarchical linear regression to predict variance in functional capacity. RESULTS: Beyond the impact of education and premorbid intellectual function, better memory and fluid reasoning predicted better functional performance. CONCLUSIONS: Although our cross-sectional design does not permit causal inference, it is possible that interventions targeting memory and fluid reasoning may improve functional ability in individuals experiencing homelessness.

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.

Identification of RP-6685, an Orally Bioavailable Compound that Inhibits the DNA Polymerase Activity of Polθ.

DNA polymerase theta (Polθ) is an attractive synthetic lethal target for drug discovery, predicted to be efficacious against breast and ovarian cancers harboring BRCA-mutant alleles. Here, we describe our hit-to-lead efforts in search of a selective inhibitor of human Polθ (encoded by POLQ). A high-throughput screening campaign of 350,000 compounds identified an 11 micromolar hit, giving rise to the N2-substituted fused pyrazolo series, which was validated by biophysical methods. Structure-based drug design efforts along with optimization of cellular potency and ADME ultimately led to the identification of RP-6685: a potent, selective, and orally bioavailable Polθ inhibitor that showed in vivo efficacy in an HCT116 BRCA2-/- mouse tumor xenograft model.

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.

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.

Factors influencing thigh muscle volume change with cycling exercises in acute spinal cord injury - a secondary analysis of a randomized controlled trial.

Objective: To conduct a per-protocol analysis on thigh muscle volume outcomes from the Spinal Cord Injury and Physical Activity (SCIPA) Switch-On Trial.Design: Secondary analysis from an assessor-blind randomized, controlled trial.Setting: Four acute/sub-acute hospitals in Australia and New Zealand.Participants: 24 adults (1 female) within four weeks of motor complete or incomplete spinal cord injury (SCI)Intervention: Functional electrical stimulation-assisted cycling (FESC) or passive cycling (PC) 4x/week for 12 weeks.Outcome Measures: Whole thigh and muscle group volumes calculated from manually segmented MR images.Results: 19/24 participants completed ≥ twelve weeks of the intervention. Five participants experienced hypertrophy (4 FESC; 1 PC) and eight attenuation of atrophy (<20% volume loss) (3 FESC; 5 PC) in thigh muscle volume. Six participants were non-responders, exhibiting atrophy >20% (3 FESC; 3 PC). Mean (SD) change for FESC was -2.3% (25.3%) and PC was -14.0% (12.3%). After controlling for baseline muscle volumes, a strong significant correlation was found between mean weekly exercise frequency and quadriceps and hamstring volumes (r=6.25, P=0.006), regardless of mode. Average watts was highly correlated to quadriceps volumes only (r=5.92, P=0.01), while total number of sessions was strongly correlated with hamstring volumes only (r=5.91, P=0.01).Conclusion: This per-protocol analysis of FESC and PC early after SCI reports a partial response in 42% and a beneficial response in 25% of patients who completed 12 weeks intervention, regardless of mode. Strong correlations show a dose-response according to exercise frequency. Characteristics of non-responders are discussed to inform clinical decision-making.

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.