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Catherine R Jutzeler,1–3 Freda M Warner,1,2 Jacquelyn J Cragg,1,3 Jenny Haefeli,4 J Scott Richards,5 Sven R Andresen,6 Nanna B Finnerup,7,8 Catherine Mercier,9 John LK Kramer1,2 1Faculty of Medicine, ICORD, University of British Columbia, Vancouver, BC, Canada; 2Faculty of Education, School of Kinesiology, University of BC, Vancouver, BC, Canada; 3Faculty of Medicine, Spinal Cord Injury Center, University Hospital Balgrist, University of Zurich, Zurich, Switzerland; 4Weill Institute for Neurosciences, Department of Neurological Surgery, Brain and Spinal Injury Center, University of California, San Francisco, CA, USA; 5Department of Physical Medicine and Rehabilitation, University of Alabama at Birmingham, Birmingham, AL, USA; 6Spinal Cord Injury Centre of Western Denmark, Department of Neurology, Regional Hospital of Viborg, Viborg, Denmark; 7Danish Pain Research Centre, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark; 8Department of Neurology, Aarhus University Hospital, Aarhus, Denmark; 9Center for Interdisciplinary Research in Rehabilitation and Social Integration, Québec, QC, Canada Background: Understanding factors associated with high placebo responses in clinical trials increases the likelihood of detecting a meaningful treatment effect. The aim of the present study was to identify subject-level factors that contribute to placebo variability in patients with neuropathic pain due to spinal cord injury (SCI).Methods: Multiple regression analysis of patient data from randomized, double-blind, placebo-controlled trials (duration >4 weeks) involving individuals with SCI was performed. Patient demographics, as well as injury and pain characteristics were examined for their association with changes in pain rating from baseline to the end of the trial (i.e., placebo response). The overall effect of individual predictors was quantified with meta-analysis statistics.Results: A total of 276 patients with SCI from six studies were included in the analysis. Based on the meta-analysis of subject-level predictors, larger placebo responses were associated with male subjects (β=0.635; standard error [SE]=0.262; p=0.016) and higher baseline pain (β=−0.146; SE=0.073; p=0.044). There were no significant effects for injury characteristics (i.e., severity, level, and time since injury) or pain characteristics (i.e., location and evoked). No significant publication bias was detected.Conclusion: The current meta-analysis of individual patient data demonstrated the importance of sex and baseline pain intensity on changes in pain ratings in the placebo arm of SCI central neuropathic pain randomized controlled clinical trials. Overall, our findings indicate that placebo responses occur independent of injury characteristics. Keywords: placebo response, clinical trial, spinal cord injury, neuropathic pain

Introduction: Traumatic spinal cord injury (tSCI) is a debilitating neurological condition resulting in lifelong disability for many individuals. The primary objectives of our study were to describe national trends in incident emergency department (ED) visits for tSCI among children (less than 21 years) in the United States, and to determine the proportion of visits that resulted in immediate hospitalization each year, including stratified by age and sex. Secondary objectives were to examine associations between select characteristics and hospitalization following tSCI, as well as to assess sports-related tSCIs over time, including by individual sport and geographic region., Methods: We used the Healthcare Cost and Utilization Project Nationwide Emergency Department Sample to identify ED visits among children between January 2016 and December 2020 for incident tSCI. Diagnosis codes were used to identify tSCI and sports-related injury etiologies. Census Bureau data were used to approximate annual rates of pediatric ED visits for tSCI per 100,000 children. Unconditional logistic regression modeling assessed whether select factors were associated with hospital admission., Results: We found that the annual ED visit rate for tSCI remained relatively stable between 2016 and 2020, with approximately 2,200 new all-cause pediatric ED visits for tSCI annually. Roughly 70% of ED visits for tSCI resulted in hospitalization; most ED visits for tSCI were by older children (15-20 years) and males, who were also more often admitted to the hospital. Notable secondary findings included: (a) compared with older children (15-20 years), younger children (10-14 years) were less likely to be hospitalized immediately following an ED visit for tSCI; (b) patient sex and race were not associated with hospital admission; and (c) American tackle football was the leading cause of sports-related ED visits for tSCI among children. Our findings also suggest that the proportion of sports-related tSCI ED visits may have increased in recent years., Discussion: Future research should further examine trends in the underlying etiologies of pediatric tSCI, while assessing the effectiveness of new and existing interventions aimed at tSCI prevention., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Crispo, Liu, Noonan, Thorogood, Kwon, Dvorak, Thibault, Willis and Cragg.)

Open data sharing of clinical research aims to improve transparency and support novel scientific discoveries. There are also risks, including participant identification and the potential for stigmatization. The perspectives of persons participating in research are needed to inform open data-sharing policies. The aim of the current study was to determine perspectives on data sharing in persons with spinal cord injury (SCI), including risks and benefits, and types of data people are most willing to share. A secondary aim was to examine predictors of willingness to share data. Persons with SCIs in the United States and Canada completed a survey developed and disseminated through various channels, including our community partner, the North American Spinal Cord Injury Consortium. The study collected data from 232 participants, with 52.2% from Canada and 42.2% from the United States, and the majority completed the survey in English. Most participants had previously participated in research and had been living with an SCI for ≥5 years. Overall, most participants reported that the potential benefits of data sharing outweighed the negatives, with persons with SCI seen as the most trustworthy partners for data sharing. The highest levels of concern were that information could be stolen and companies might use the information for marketing purposes. Persons with SCI were generally supportive of data sharing for research purposes. Clinical trials should consider including a statement on open data sharing in informed consents to better acknowledge the contribution of research participants in future studies., Competing Interests: No competing financial interests exist., (© Freda M. Warner et al., 2023; Published by Mary Ann Liebert, Inc.)

Objectives: Despite unregulated amphetamine use increasing, there are limited data on related emergency department (ED) visits in Canada. Our primary objective was to examine trends in amphetamine-related ED visits over time in Ontario, including by age and sex. Secondary objectives were to examine whether patient characteristics were associated with ED revisit within 6 months., Methods: Using administrative claims and census data, we calculated annual patient- and encounter-based rates of amphetamine-related ED visits from 2003 to 2020 among individuals 18+ years of age. We also performed a retrospective cohort study of individuals with amphetamine-related ED visits between 2019 and 2020 to determine whether select factors were associated with ED revisit within 6 months. Multivariable logistic regression modelling was used to measure associations., Results: The population-based rate of amphetamine-related ED visits increased nearly 15-fold between 2003 (1.9/100,000 Ontarians) and 2020 (27.9/100,000 Ontarians). Seventy-five percent of individuals returned to the ED for any reason within 6 months. Psychosis and use of other substances were both independently associated with ED revisit for any reason within 6 months (psychosis: AOR = 1.54, 95% CI = 1.30-1.83; other substances: AOR = 1.84, 95% CI = 1.57-2.15), whereas having a primary care physician was negatively associated with ED revisit (AOR = 0.77, 95% CI = 0.60-0.98)., Conclusions: Increasing rates of amphetamine-related ED visits in Ontario are cause for concern. Diagnoses of psychosis and the use of other substances may serve to identify individuals who are most likely to benefit from both primary and substance-specific care., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Multiple types and classes of medications are administered in the acute management of traumatic spinal cord injury. Prior clinical studies and evidence from animal models suggest that several of these medications could modify (i.e., enhance or impede) neurological recovery. We aimed to systematically determine the types of medications commonly administered, alone or in combination, in the transition from acute to subacute spinal cord injury. For that purpose, type, class, dosage, timing, and reason for administration were extracted from two large spinal cord injury datasets. Descriptive statistics were used to describe the medications administered within the first 60 days after spinal cord injury. Across 2040 individuals with spinal cord injury, 775 unique medications were administered within the two months after injury. On average, patients enrolled in a clinical trial were administered 9.9 ± 4.9 (range 0-34), 14.3 ± 6.3 (range 1-40), 18.6 ± 8.2 (range 0-58), and 21.5 ± 9.7 (range 0-59) medications within the first 7, 14, 30, and 60 days post-injury, respectively. Those enrolled in an observational study were administered on average 1.7 ± 1.7 (range 0-11), 3.7 ± 3.7 (range 0-24), 8.5 ± 6.3 (range 0-42), and 13.5 ± 8.3 (range 0-52) medications within the first 7, 14, 30, and 60 days post-injury, respectively. Polypharmacy was commonplace (up to 43 medications per day per patient). Approximately 10% of medications were administered acutely as prophylaxis (e.g., against the development of pain or infections). To our knowledge, this was the first time acute pharmacological practices have been comprehensively examined after spinal cord injury. Our study revealed a high degree of polypharmacy in the acute stages of spinal cord injury, raising the potential to impact neurological recovery. All results can be interactively explored on the R X SCI web site ( https://jutzelec.shinyapps.io/RxSCI/ ) and GitHub repository ( https://github.com/jutzca/Acute-Pharmacological-Treatment-in-SCI/ )., (© 2023. The Author(s).)

Background: Traumatic spinal cord injury (tSCI) is a debilitating neurological condition often associated with lifelong disability. Despite this, there are limited data on pediatric tSCI epidemiology in the United States., Objectives: Our primary objective was to estimate tSCI hospitalization rates among children, including by age, sex, and race. Secondary objectives were to characterize tSCI hospitalizations and examine associations between sociodemographic characteristics and tSCI etiology., Methods: We used the 2016 Kids' Inpatient Database to examine tSCI hospitalizations among children (<21 years). Descriptive statistics were used to report individual and care setting characteristics for initial tSCI hospitalizations. We used Census Bureau data to estimate tSCI hospitalization rates (number of pediatric tSCI hospitalizations / number of US children) and logistic regression modeling to assess associations between documented sociodemographic characteristics and injury etiology., Results: There were 1.48 tSCI admissions per 100,000 children; highest rates of hospitalization involved older (15-20 years), male, and Black children. Hospitalization involving male (adjusted odds ratio [AOR] 0.43; 95% CI, 0.33-0.58) or Black (AOR 0.37; 95% CI, 0.25-0.55) children were less likely to involve a motor traffic accident. Hospitalizations of Black children were significantly more likely to have a diagnosis of tSCI resulting from a firearm incident (AOR 18.97; 95% CI, 11.50-31.28) or assault (AOR 11.76; 95% CI, 6.75-20.50) compared with hospitalizations of White children., Conclusion: Older, male, and Black children are disproportionately burdened by tSCI. Implementation of broad health policies over time may be most effective in reducing pediatric tSCI hospitalizations and preventable injuries., Competing Interests: Conflicts of Interest The authors report no conflicts of interest., (© 2022 American Spinal Injury Association.)

Objectives: Although amphetamine use is a growing health problem in the USA, there are limited data on amphetamine-related hospitalisations. The primary objective of our study was to examine trends in amphetamine-related hospitalisations in the USA between 2003 and 2014, including by age and sex. Our secondary objectives were to examine whether demographic, clinical and care setting characteristics were associated with select outcomes of amphetamine-related hospitalisations, including in-hospital mortality, prolonged length of stay and leaving against medical advice., Design, Setting and Participants: Using the 2003-2014 National Inpatient Sample, we estimated the rate of amphetamine-related hospitalisations for each year in the USA among individuals 18+ years of age, stratified by age and sex. Subgroup analyses examined hospitalisations due to amphetamine causes. Unconditional logistic regression modelling was used to estimate the adjusted odds of admission outcomes for sociodemographic, clinical and hospital indicators., Primary and Secondary Outcomes: Our primary outcome was amphetamine-related hospitalisations between 2003 and 2014; secondary outcomes included in-hospital mortality, prolonged length of stay and leaving against medical advice., Results: Amphetamine-related hospitalisation rates increased from 27 to 69 per 100 000 population between 2003 and 2014. Annual rates were consistently greater among younger (18-44 years) individuals and men. Regional differences were observed, with admission to Western hospitals being associated with increased mortality (adjusted OR, AOR 5.07, 95% CI 1.22 to 21.04) and shorter (0-2 days) lengths of stay (AOR 0.70, 95% CI 0.58 to 0.83) compared with Northeast admissions. Males (AOR 1.26, 95% CI 1.15 to 1.38; compared with females) and self-pay (AOR 2.30, 95% CI 1.90 to 2.79; compared with private insurance) were associated with leaving against medical advice., Conclusions: Increasing rates of amphetamine-related hospitalisation risk being overshadowed by other public health crises. Regional amphetamine interventions may offer the greatest population health benefits. Future studies should examine long-term outcomes among patients hospitalised for amphetamine-related causes., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The epidemiological international landscape of traumatic spinal cord injury (SCI) has evolved over the last decades along with given inherent differences in acute care and rehabilitation across countries and jurisdictions. However, to what extent these differences may influence neurological and functional recovery as well as the integrity of international trials is unclear. The latter also relates to historical clinical data that are exploited to inform clinical trial design and as potential comparative data., Methods: Epidemiological and clinical data of individuals with traumatic and ischemic SCI enrolled in the European Multi-Center Study about Spinal Cord Injury (EMSCI) were analyzed. Mixed-effect models were employed to account for the longitudinal nature of the data, efficiently handle missing data, and adjust for covariates. The primary outcomes comprised demographics/injury characteristics and standard scores to quantify neurological (i.e., motor and sensory scores examined according to the International Standards for the Neurological Classification of Spinal Cord Injury) and functional recovery (walking function). We externally validated our findings leveraging data from a completed North American landmark clinical trial., Results: A total of 4601 patients with acute SCI were included. Over the course of 20 years, the ratio of male to female patients remained stable at 3:1, while the distribution of age at injury significantly shifted from unimodal (2001/02) to bimodal distribution (2019). The proportional distribution of injury severities and levels remained stable with the largest percentages of motor complete injuries. Both, the rate and pattern of neurological and functional recovery, remained unchanged throughout the surveillance period despite the increasing age at injury. The findings related to recovery profiles were confirmed by an external validation cohort (n=791). Lastly, we built an open-access and online surveillance platform ("Neurosurveillance") to interactively exploit the study results and beyond., Conclusions: Despite some epidemiological changes and considerable advances in clinical management and rehabilitation, the neurological and functional recovery following SCI has remained stable over the last two decades. Our study, including a newly created open-access and online surveillance tool, constitutes an unparalleled resource to inform clinical practice and implementation of forthcoming clinical trials targeting neural repair and plasticity in acute spinal cord injury., (© 2022. The Author(s).)

Study Design: Retrospective cross-sectional epidemiological study., Objectives: Previous studies have quantified longitudinal psychological morbidity in individuals with spinal cord injury (SCI) relative to uninjured individuals. However, there is limited information regarding how lifestyle and socioeconomic factors are associated with mental health conditions in individuals with SCI. This study aims to quantify and compare mental health and suicidal thoughts in people with and without SCI, and examine the associations between mental health, suicidal thoughts, sex, age, lifestyle, and socioeconomic factors., Setting: Canada., Methods: The 2010 Canadian Community Health Survey (n > 40,000) was used, which includes several measures assessing mental health and suicidal thoughts. Bivariate and multivariate logistic regressions were performed and odds ratios with corresponding 95% confidence intervals were estimated. Sensitivity analyses were performed to evaluate the effect of covariates on reported effect sizes., Results: People with SCI had higher odds of having mood (3.6) and anxiety disorders (2.5), suicidal thoughts (2.3), self-perceived stress (1.9), and depression (4.4); in addition to lower odds of having good self-perceived mental health (0.24) and satisfaction with life (0.25). These differences persisted after adjusting for age, sex, lifestyle, and socioeconomic factors. Lower household income, fruit and vegetable consumption, and physical activity levels, and increased smoking use were associated with poorer mental health in individuals with SCI., Conclusions: Mental health is poorer in those with SCI when compared with the general population. Those with SCI exhibit a unique profile of lifestyle and socioeconomic factors that are associated with poorer mental health and increased suicidal thoughts., (© 2022. The Author(s), under exclusive licence to International Spinal Cord Society.)

Physical activity is a powerful modifiable risk factor for disease and mortality. Physical activity levels in people with spinal cord injury (SCI) have not been quantified relative to uninjured individuals in a large population-based sample. We aimed to quantify and compare physical activity in people with and without SCI, and to examine the associations between physical activity, lifestyle, and socioeconomic factors. The 2010 Canadian Community Health Survey (n > 57,000) was used, which includes three measures that assess physical activity levels (i.e., leisure time activity frequency, leisure time activity intensity, and transportation time activity intensity). Bivariable and multivariable logistic regressions were performed and odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were estimated. The odds of physical activity in people with SCI were 0.43 (95% CI 0.3-0.61), 0.53 (95% CI 0.36-0.75), and 0.42 (95% CI 0.28-0.61), across the three measures of physical activity, respectively. These differences persisted after adjustment for lifestyle, comorbidities, and socioeconomic factors. Physical activity is reduced in the SCI population compared with the general population. This knowledge is important to direct future research and guide the allocation of health care resources., (© 2022. The Author(s).)

Accurate safety information in published clinical trials guides the assessment of risk-benefit, as well as the design of future clinical trials. Comprehensive reporting of adverse events, toxicity, and discontinuations from acute spinal cord injury clinical trials is an essential step in this process. Here, we sought to assess the degree of "satisfactoriness" of reporting in past clinical trials in spinal cord injury. A review of citations from MEDLINE and EMBASE identified eligible clinical trials in acute (within 30 days) spinal cord injury. English language studies, published between 1980 and 2020, with sensory, motor, or autonomic neurological assessments as the primary outcome measure were eligible for inclusion. Criteria were then established to qualify the safety reporting as satisfactory (i.e., distinguished severe/life-threatening events), partially satisfactory, or unsatisfactory (i.e., only mentioned in general statements, or reported but without distinguishing severe events). A total of 40 trials were included. Satisfactory reporting for clinical adverse events was observed in 30% of trials; partially satisfactory was achieved by 10% of the trials, and the remaining 60% were unsatisfactory. The majority of trials were determined to be unsatisfactory for the reporting of laboratory-defined toxicity (82.5%); only 17.5% were satisfactory. Discontinuations were satisfactorily reported for the majority of trials (80%), with the remaining partially satisfactory (5%) or unsatisfactory (15%). Reporting of safety in clinical trials for acute spinal cord injury is suboptimal. Due to the complexities of acute spinal cord injury (e.g., polytrauma, multiple systems affected), tailored and specific standards for tracking adverse events and safety reporting should be established.

Study Design: Multicentre, cross-sectional study., Objectives: To identify which markers of obesity, injury characteristics and autonomic function variables are related to cardiovascular disease (CVD) risk after spinal cord injury (SCI), and establish cut-points for detection and risk management., Setting: Eight SCI rehabilitation centres in the Netherlands., Methods: Individuals (n = 257) with a traumatic, chronic (≥10 years) SCI, with age at injury between 18 and 35 years, completed a self-report questionnaire and a one-day visit to a rehabilitation centre for testing. Three anthropometric measures were tested: body mass index (BMI); waist circumference (WC); and waist-to-height ratio (WHtR). Injury characteristics included: American Spinal Injury Association impairment scale (AIS); duration of injury (DOI); and neurological level of injury (LOI). Cardiovascular autonomic function was assessed from peak heart rate during maximal exercise (HR peak ). Systolic arterial pressure (SAP) and aerobic capacity (VO 2peak ) were also determined. CVD risk was calculated using the Framingham risk score (FRS)., Results: All anthropometric variables were associated with FRS, with WC showing the strongest correlation (r = 0.41, p < 0.001) and greatest area under the curve (0.73) for 10-year CVD risk (%). WC, DOI, SAP, HR peak , LOI, and VO 2peak (variable importance: 0.81, 1.0, 0.98, 0.98, 0.66, 0.68, respectively) were important predictive variables for 10-year CVD risk in individuals with SCI., Conclusions: We confirm that WC is a simple, practical measure of CVD risk, and along with DOI and markers of cardiovascular autonomic function, plays a role in the increased CVD risk following SCI.

Spinal cord injury results in devastating neurological deficits accompanied by lifelong disability and significant economic burden. While the development of novel compounds or cell-based interventions for spinal cord injury is unquestionably worthwhile, a complementary approach examines current standards of care and the degree to which these can be optimized to benefit long-term neurological function. Numerous classes of drugs, already in use in the acute phase of spinal cord injury, are intriguing because they (1) readily cross the blood-spinal cord barrier to modulate activity in the central nervous system and (2) are administered during a window of time in which neuroprotection, and even some repair, are feasible. Here, we review a rare case of convergent lines of evidence from both preclinical and human studies to support the early administration of a class of drug (ie, gabapentinoids) to both foster motor recovery and reduce the severity of neuropathic pain.

Objectives: To describe an approach using concomitant medication log records for the construction of treatment episodes. Concomitant medication log records are routinely collected in clinical studies. Unlike prescription and dispensing records, concomitant medication logs collect utilisation data. Logs can provide information about drug safety and drug repurposing., Design: A prospective multicentre, multicohort observational study., Setting: Twenty-one clinical sites in the USA, Europe, Israel and Australia., Participants: 415 subjects from the de novo cohort of the Parkinson's Progression Markers Initiative., Methods: We construct treatment episodes of concomitant medication use. The proposed approach treats temporal gaps as a stoppage of medication and temporal overlaps as simultaneous use or changes in dose. Log records with no temporal gaps were combined into a single treatment episode., Results: 5723 concomitant medication log records were used to construct 3655 treatment episodes for 65 medications. There were 405 temporal gaps representing a stoppage of medication; 985 temporal overlaps representing simultaneous regimens of the same medication and 2696 temporal overlaps representing a change in dose regimen. The median episode duration was 37 months (IQ interval: 11-73 months)., Conclusions: The proposed approach for constructing treatment episodes offers a method of estimating duration and dose of treatment from concomitant medication log records. The accompanying recommendations guide log data collection to improve their quality for drug safety and drug repurposing., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The objective of our study was to determine whether treatment with baclofen is neurologically safe with respect to exposure during recovery from spinal cord injury. We performed a secondary longitudinal analysis of a cohort of adult patients with traumatic acute spinal cord injury. Cumulative baclofen dose was computed over the first 4 weeks following injury from concomitant medication information from a completed clinical trial. The main outcome measure was neurologic status, which was assessed over 52 weeks with "marked recovery" defined as the conversion to higher sensory and motor function. To complete the drug safety profile, drug toxicity was assessed with assays from standard blood work. Multivariable Cox regression was used to compute hazard ratios (HRs) and 95% confidence intervals (CIs). Of the cohort (n = 651), 18% (n = 115) received baclofen within 4 weeks post injury. Baclofen use was associated with higher rates of marked neurologic recovery, even after adjustment for injury severity (HR = 2.1, 95% CI 1.5-3.0 for high dose vs none). Baclofen exposure was not associated with liver or renal side effects. The use of other medications indicated for spasticity was not associated with neurological outcomes. Overall, this longitudinal analysis provides level 3 evidence on the neurologic safety of baclofen and potential beneficial effects on recovery in the early days after acute traumatic spinal cord injury. The usefulness of concomitant medication files from completed clinical trials is highlighted. We also highlight the importance of incorporating logical patient questions and neurological outcomes into research addressing drug safety.

Small-scale studies indicate that spinal cord injury (SCI) may lead to significant gastrointestinal and bladder dysfunction. However, how the prevalence of chronic disease related to these dysfunctions compares with non-SCI individuals and whether there are robust relationships to level and severity of injury are still unclear. Here, our goal was to provide high-level evidence on the association between bladder and gastrointestinal dysfunction and SCI using population-level data from the Canadian Community Health Survey (CCHS) and the SCI Community Survey. Data from more than 60,000 individuals in the 2010 CCHS and 1500 individuals with SCI from the SCI Community Survey were analyzed. We used bi-variable and multi-variable logistic regression to examine relationships between explanatory and outcome variables. We found that SCI was associated with increased odds of urinary incontinence (adjusted odds ratio [aOR] = 5.0, 95% confidence interval [CI]: 3.4-7.1), bowel disorders (aOR = 2.3, CI: 1.5-3.4), as well as gastric ulcers (aOR: 3.3, CI: 2.1-4.8), even after adjusting for key confounding variables. Additionally, we found that complete SCI was associated with increased odds of urinary tract infections (aOR = 2.0, CI: 1.6-2.5) and bowel incontinence (aOR = 2.1, CI: 1.7-2.6). Individuals with SCI are at increased odds for having bladder and gastrointestinal dysfunction, certain aspects of which are dependent on the level and severity of injury. Targeted intervention and prevention strategies to manage bladder and bowel problems after SCI should be a priority for both caregivers and policy makers.

Recent temporal trends in the population prevalence of chronic pain in Canada on a national and provincial level are unknown. Five cycles of the Canadian Community Health Survey (2000/2001, 2007/2008, 2009/2010, 2011/2012, and 2013/2014) were used to derive population-based estimates of the self-reported prevalence of chronic pain. Sensitivity analyses examined chronic pain prevalence among those reporting no other chronic health conditions. The prevalence of chronic pain among the general Canadian population increased by almost 4.0% (to 21.0%) in 2011/2012, after being in the range of 15.7 to 17.2% from 2000 to 2009/2010. The sudden increase in prevalence was observed 1) across all provinces in Canada, 2) in all age categories, and 3) among Canadians with no other chronic health conditions. Increasing chronic pain prevalence in Canada, most significantly occurring between 2010 and 2012, and including among healthy and young individuals, emphasizes the need for targeted research and resources to help alleviate chronic pain. PERSPECTIVE: This study uncovers a significant increase in chronic pain prevalence in Canada between 2009/2010 and 2011/2012, driven by younger Canadians that are free of the most common chronic health conditions. This discovery emphasizes the importance of further directed research and resources to help mitigate the trend of increasing chronic pain., (Copyright © 2018 the American Pain Society. Published by Elsevier Inc. All rights reserved.)

The translation of therapeutic interventions to humans with spinal cord injury with the goal of promoting growth and repair in the central nervous system could, inadvertently, drive mechanisms associated with the development of neuropathic pain. A framework is needed to evaluate the probability that a therapeutic intervention for acute spinal cord injury modifies the progression of neuropathic pain. We analyzed a large, longitudinal dataset from the European Multi-Center Study about Spinal Cord Injury (EMSCI) and compared these observations with a previously published Swedish/Danish cohort. A meta-analysis was performed to produce aggregate estimates for the transition period between 1-6 months and the transition period between 1-12 months after injury. A secondary analysis used logistic regression to explore associations between the progression of neuropathic pain and demographics, pain characteristics, and injury characteristics. For overall neuropathic pain, 72% presenting with pain symptoms at one month reported persisting symptoms at six months, and 23% who did not have neuropathic pain at one month later had it develop. From 1-12 months, there was a similar likelihood of pain persisting (69%) and slightly higher rate of pain developing (36%). Characteristics that were significantly associated with the progression of pain included age and sensory and motor preservation. We provide historical benchmarks for estimating the progression of neuropathic pain during the first year after acute SCI. This information will be useful for comparison and evaluating safety during early phase acute spinal cord injury trials.

Background: Autonomic dysreflexia is a severe and potentially life-threatening condition in patients with spinal cord injury, as it can lead to myocardial ischemia, brain hemorrhage, or even death. Urodynamic investigation is the gold standard to assess neurogenic lower urinary tract dysfunction due to spinal cord injury and reveal crucial pathological findings, such as neurogenic detrusor overactivity. However, neurogenic detrusor overactivity and urodynamic investigation are known to be leading triggers of autonomic dysreflexia. Therefore, we aimed to determine predictors of autonomic dysreflexia in individuals with spinal cord injury during urodynamic investigation., Methods: This prospective cohort study included 300 patients with spinal cord injuries and complete datasets of continuous non-invasive cardiovascular monitoring, recorded during same session repeat urodynamic investigation. We used logistic regression to reveal predictors of autonomic dysreflexia during urodynamic investigation., Results: We found that level of injury and presence of neurogenic detrusor overactivity were the only two independent significant predictors for autonomic dysreflexia during urodynamic investigation. A lesion at spinal segment T6 or above (odds ratio (OR) 5.5, 95% CI 3.2-9.4) compared to one at T7 or below, and presence of neurogenic detrusor overactivity (OR 2.7, 95% confidence interval (CI) 1.4-4.9) were associated with a significant increased odds of autonomic dysreflexia during urodynamic investigation. Both odds persisted after adjustment for age, sex, and completeness and stage of injury (adjusted OR (AOR) 6.6, 95% CI 3.8-11.7, and AOR 2.2, 95% CI 1.1-4.5, respectively). Further stratification by lesion level showed level-dependent significantly increased adjusted odds of autonomic dysreflexia, i.e., from C1-C4 (AOR 16.2, 95% CI 5.9-57.9) to T4-T6 (AOR 2.6, 95% CI 1.3-5.2), compared to lesions at T7 or below., Conclusions: In patients with neurogenic lower urinary tract dysfunction due to spinal cord injury, autonomic dysreflexia is independently predicted by lesion level and presence of neurogenic detrusor overactivity. Considering the health risks associated with autonomic dysreflexia, such as seizures, stroke, retinal bleeding, or even death, we recommend both continuous cardiovascular monitoring during urodynamic investigation in all spinal cord-injured patients with emphasis on those with cervical lesions, and appropriate neurogenic detrusor overactivity treatment to reduce the probability of potentially life-threatening complications., Trial Registration: ClinicalTrials.gov, NCT01293110 .

Background: The prevalence of pain among people with a variety of individual neurological conditions has been estimated. However, information is limited about chronic pain among people with neurological conditions overall, and about the conditions for which chronic pain is most prevalent. To fill these information gaps, a common method of pain assessment is required., Data and Methods: The data are from the Survey on Living with Neurological Conditions in Canada, a cross-sectional national survey. Based on self-reports, chronic pain was assessed for 16 neurological conditions. Multivariable logistic regression was used to produce odds ratios and 95% confidence intervals (CIs)., Results: Close to 1.5 million individuals aged 15 or older who lived in private households reported having been diagnosed with a neurological condition. The overall prevalence of chronic pain for the 16 neurological conditions combined was 36% (95% CI: 31% to 42%). The odds of chronic pain were significantly elevated among individuals with spinal cord trauma., Discussion: Chronic pain is highly prevalent among people with neurological conditions, particularly those with spinal cord trauma. These results suggest a need to target health services and direct research to improved pain management, and thereby reduce the burden of neurological disease.

Background: There is a need to identify reliable biomarkers of spinal cord injury recovery for clinical practice and clinical trials., Objective: Our objective was to correlate serum albumin levels with spinal cord injury neurological outcomes., Methods: We performed a secondary analysis of patients with traumatic spinal cord injury (n = 591) participating in the Sygen clinical trial. Serum albumin concentrations were obtained as part of routine blood chemistry analysis, at trial entry (24-72 hours), 1, 2, and 4 weeks after injury. The primary outcomes were "marked recovery" and lower extremity motor scores, derived from the International Standards for the Neurological Classification of Spinal Cord Injury. Data were analyzed with multivariable logistic and linear regression to adjust for potential confounders., Results: Serum albumin was significantly associated with spinal cord injury neurological outcomes. Higher serum albumin concentrations at 1, 2, and 4 weeks were associated with higher 52-week lower extremity motor score. Similarly, the odds of achieving "marked neurological recovery" was greater for individuals with higher serum albumin concentrations. The association between serum albumin concentrations and neurological outcomes was independent of initial injury severity, treatment with GM-1, and polytrauma., Conclusions: In spinal cord injury, serum albumin is an independent marker of long-term neurological outcomes. Serum albumin could serve as a feasible biomarker for prognosis at the time of injury and stratification in clinical trials.

Recovery from acute spinal cord injury (SCI) is characterized by extensive heterogeneity, resulting in uncertain prognosis. Reliable prediction of recovery in the acute phase benefits patients and their families directly, as well as improves the likelihood of detecting efficacy in clinical trials. This issue of heterogeneity is not unique to SCI. In fields such as traumatic brain injury, Parkinson's disease, and amyotrophic lateral sclerosis, one approach to understand variability in recovery has been to make clinical trial data widely available to the greater research community. We contend that the SCI community should adopt a similar approach in providing open access clinical trial data.

The anticonvulsant pregabalin promotes neural regeneration in a mouse model of spinal cord injury (SCI). We have also previously observed that anticonvulsants improve motor outcomes following human SCI. The present study examined the optimal timing and type of anticonvulsants administered in a large, prospective, multi-center, cohort study in acute SCI. Mixed-effects regression techniques were used to model total motor scores at 1, 3, 6, and 12 months post injury. We found that early (not late) administration of anticonvulsants significantly improved motor recovery (6.25 points over 1 year). The beneficial effect of anticonvulsants remained significant after adjustment for differences in 1-month motor scores and injury characteristics. A review of a subset of patients revealed that gabapentinoids were the most frequently administrated anticonvulsant. Together with preclinical findings, intervention with anticonvulsants represents a potential pharmacological strategy to improve motor function after SCI., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Background Approximately 60% of patients suffering from acute spinal cord injury (SCI) develop pain within days to weeks after injury, which ultimately persists into chronic stages. To date, the consequences of pain after SCI have been largely examined in terms of interfering with quality of life. Objective The objective of this study was to examine the effects of pain and pain management on neurological recovery after SCI. Methods We analyzed clinical data in a prospective multicenter observational cohort study in patients with SCI. Using mixed effects regression techniques, total motor and sensory scores were modelled at 1, 3, 6, and 12 months postinjury. Results A total of 225 individuals were included in the study (mean age: 45.8 ± 18 years, 80% male). At 1 month postinjury, 28% of individuals with SCI reported at- or below-level neuropathic pain. While pain classification showed no effect on neurological outcomes, individuals administered anticonvulsant medications at 1 month postinjury showed significant reductions in pain intensity (2 points over 1 year; P < .05) and greater recovery in total motor scores (7.3 points over 1 year; P < .05). This drug effect on motor recovery remained significant after adjustment for injury level and injury severity, pain classification, and pain intensity. Conclusion While initial pain classification and intensity did not reveal an effect on motor recovery following acute SCI, anticonvulsants conferred a significant beneficial effect on motor outcomes. Early intervention with anticonvulsants may have effects beyond pain management and warrant further studies to evaluate the therapeutic effectiveness in human SCI., (© The Author(s) 2016.)

Migraine headaches are a common neurological condition, negatively impacting health and quality of life. The association between migraines and spinal cord injury (SCI) is intriguing to consider from the perspective that migraine headaches may be acquired in response to damage in the spinal cord [corrected].The primary objective of this study was to further examine the association between SCI and migraine headache, controlling for potential confounding variables. A secondary objective was to determine the impact of migraine headaches on self-perceived health. Data from a sample of 61,047 participants were obtained from the cross-sectional Canadian Community Health Survey. Multivariable logistic regression was used to explore the association between SCI and migraine headache using probability weights and adjusting for confounders. The multivariable age- and sex-adjusted model revealed a strong association between SCI and migraine headache, with an adjusted odds ratio for migraine of 4.82 (95% confidence interval [3.02, 7.67]) among those with SCI compared to those without SCI. Further, individuals who experienced both SCI and migraine tended to report poorer perceived general health compared with the other groups (i.e., SCI and no migraine). In conclusion, this study established a strong association between SCI and migraine headache. Further research is needed to explore the possible mechanisms underlying this relationship. Improvements in clinical practice to minimize this issue could result in significant improvements in quality of life.

Study Design: Observational cross-sectional study., Objectives: Body mass index (BMI), measured as a ratio of weight (Wt) to the square of height (Wt/Ht(2)), waist circumference (WC) and waist-to-height ratio (WHtR) are common surrogate measures of adiposity. It is not known whether alternate scaling powers for height might improve the relationships between these measures and indices of obesity or cardiovascular disease (CVD) risk in individuals with spinal cord injury (SCI). We aimed to estimate the values of 'x' that render Wt/Ht(x) and WC/Ht(x) maximally correlated with dual energy x-ray absorptiometry (DEXA) total and abdominal body fat and Framingham Cardiovascular Risk Scores., Setting: Canadian public research institution., Methods: We studied 27 subjects with traumatic SCI. Height, Wt and body fat measurements were determined from DEXA whole-body scans. WC measurements were also obtained, and individual Framingham Risk Scores were calculated. For values of 'x' ranging from 0.0 to 4.0, in increments of 0.1, correlations between Wt/Ht(x) and WC/Ht(x) with total and abdominal body fat (kg and percentages) and Framingham Risk Scores were computed., Results: We found that BMI was a poor predictor of CVD risk, regardless of the scaling factor. Moreover, BMI was strongly correlated with measures of obesity, and modification of the scaling factor from the standard (Wt/Ht(2)) is not recommended. WC was strongly correlated with both CVD risk and obesity, and standard measures (WC and WHtR) are of equal predictive power., Conclusion: On the basis of our findings from this sample, alterations in scaling powers may not be necessary in individuals with SCI; however, these findings should be validated in a larger cohort.

Study Design: Despite significant progress in bladder management, urinary tract infections (UTIs) are still common among individuals with spinal cord injury (SCI), and could negatively impact their health and quality of life. However, there are no data available on bladder management and frequency of UTIs among elite athletes with SCI., Methods: Athletes were assessed during the London 2012 Paralympic Games and 2013 Paracycling World Championships. Athletes completed the standard form of the International Standards to Document remaining Autonomic Functions after SCI, along with the standardized Autonomic Function Questionnaire., Results: A total of 61 (age=35.5±7.7 years (mean±s.d.); time since injury=16.0±7.6 years) elite athletes from 15 countries with traumatic SCI and who used clean intermittent catheterization were included in this study. The majority (75%) were from developed nations. Athletes catheterized on average 6±2 times per day. We found that individuals who reused catheters experienced more frequent UTIs (P<0.001). We also demonstrated that 83% of individuals from developed nations never reused a single-use catheter, whereas only 27% of individuals from developing nations used a new catheter each time (P<0.001). We also noted a twofold increase in the frequency of UTIs in individuals from developing nations (P=0.027)., Conclusions: This study demonstrates that catheter reuse is intimately linked to UTI frequency and provides novel insight on bladder function and management in elite athletes with SCI. Reasons for catheter reuse may be due to a lack of health education and/or a lack of bladder-management resources. (Support: Craig Neilsen Foundation, ICORD, IPC).

Clinical scenario: A 37-year-old man suffered a complete spinal cord injury (C8, American Spinal Injury Association Impairment Scale [ASIA] score A) 10 years ago in a car accident. Should primary prevention of cardiovascular disease be a priority in this patient? In order to answer this question, we performed a systematic review of the literature to inform an evidence-based clinical review. The objective was to provide a comprehensive and up-to-date review of the clinical management of cardiovascular disease (CVD) and risk factors for individuals with spinal cord injury (SCI). Comprehensive literature searches were performed. The quality of each study was assessed using the Physiotherapy Evidence Database Scale for randomized controlled trials, and the Downs and Black Scale for all other studies. Levels of evidence were assigned using a modified version of Sackett's scale. Our findings indicate that CVD is a critical issue in individuals with chronic SCI. Almost all risk factors for CVD are amplified in individuals with SCI, including physical inactivity, dyslipidemia, blood pressure irregularities, abnormal glycemic control, and chronic inflammation. However, there is a paucity of high-quality literature with respect to treatment outcomes in SCI-specific study populations (a total of 22 intervention studies in all of these categories combined) that allow for the development of evidence-informed clinical practice recommendations. These limitations notwithstanding, we present a series of contemporary practice suggestions with regard to CVD event risk modification in SCI patients. For optimal outcomes, health care providers should be cognizant of these heightened CVD risk factors and the resultant increased CVD morbidity and mortality in SCI patients. Despite the absence of high-quality evidence-based treatment strategies, clinicians should re-examine their own CVD risk factor treatment strategies to better reflect contemporary practice in similar high-CVD-event-risk patients and populations.

To improve science learning, science educators' teaching tools need to address two major criteria: teaching practice should mirror our current understanding of the learning process; and science teaching should reflect scientific practice. We designed a small-group learning (SGL) model for a fourth year university neurobiology course using these criteria and studied student achievement and attitude in five course sections encompassing the transition from individual work-based to SGL course design. All students completed daily quizzes/assignments involving analysis of scientific data and the development of scientific models. Students in individual work-based (Individualistic) sections usually worked independently on these assignments, whereas SGL students completed assignments in permanent groups of six. SGL students had significantly higher final exam grades than Individualistic students. The transition to the SGL model was marked by a notable increase in 10th percentile exam grade (Individualistic: 47.5%; Initial SGL: 60%; Refined SGL: 65%), suggesting SGL enhanced achievement among the least prepared students. We also studied student achievement on paired quizzes: quizzes were first completed individually and submitted, and then completed as a group and submitted. The group quiz grade was higher than the individual quiz grade of the highest achiever in each group over the term. All students--even term high achievers--could benefit from the SGL environment. Additionally, entrance and exit surveys demonstrated student attitudes toward SGL were more positive at the end of the Refined SGL course. We assert that SGL is uniquely-positioned to promote effective learning in the science classroom.