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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

Background: The transition from hospital to home is a high-risk period. Timely follow-up care is essential to reducing avoidable harms such as adverse drug events, yet may be unattainable for patients who lack attachment to a primary care provider. Transitional care clinics (TCCs) have been proposed as a measure to improve health outcomes for patients discharged from hospital without an established provider. In this systematic review, we compared outcomes for unattached patients seen in TCCs after hospital discharge relative to care as usual., Methods: We searched the following bibliographic databases for articles published on or before August 12, 2022: MEDLINE, Cumulative Index to Nursing and Allied Health Literature, Cochrane Database of Systematic Reviews, PsycINFO, and Web of Science. Five studies were identified that examined the effects of a dedicated postdischarge clinic on emergency department (ED) visits, readmissions, and/or mortality within 90 days of discharge for patients with no attachment to a primary care provider., Results: Studies were heterogeneous in design and quality; all were from urban centers within the United States. Four of the five studies reported a reduction in either the number of ED visits or readmissions in patients seen in a TCC following hospitalization., Conclusions: TCCs may be effective in reducing hospital contacts in the period following hospital discharge in patients with no established primary care provider. Further studies are required to evaluate the health benefits attributable to the implementation of TCCs across a broad range of practice contexts, as well as the cost implications of this model., (© 2024 The Authors. Journal of Hospital Medicine published by Wiley Periodicals LLC on behalf of Society of Hospital Medicine.)

Context/objective: The risk for cardiovascular disease is amplified following spinal cord injury, but whether risk differs between the sexes remains unknown. Here, we evaluated sex differences in the prevalence of heart disease among individuals with spinal cord injury, and compared sex differences with able-bodied individuals., Design: The design was a cross-sectional study. Multivariable logistic regression analysis was conducted, using inverse probability weighting to account for the sampling method and to adjust for confounders., Setting: Canada., Participants: Individuals who participated in the national Canadian Community Health Survey., Interventions: Not applicable., Outcome Measures: Self-reported heart disease., Results: Among 354 individuals with spinal cord injury, the weighted prevalence of self-reported heart disease was 22.9% in males and 8.7% in females, with an inverse-probability weighted odds ratio of 3.44 (95% CI 1.70-6.95) for males versus females. Among 60,605 able-bodied individuals, the prevalence of self-reported heart disease was 5.8% in males and 4.0% in females, with an inverse probability weighted odds ratio of 1.62 (95% CI 1.50-1.75) for males versus females. The effect of male sex on increasing heart disease prevalence was about two times higher among individuals with spinal cord injury than able-bodied individuals (relative difference in inverse probability weighted odds ratios = 2.12, 95% CI 1.08-4.51)., Conclusion: Males with spinal cord injury exhibit a significantly higher prevalence of heart disease, compared with females with spinal cord injury. Moreover, relative to able-bodied individuals, spinal cord injury amplifies sex-related differences in heart disease. Overall, this work will inform targeted cardiovascular prevention strategies, and may also inform a better understanding of cardiovascular disease progression in both able-bodied and individuals with spinal cord injury.

We evaluated the relationship between cost-related non-adherence (CRNA) and depressive symptoms. Pooling data from the 2015, 2016, 2018, and 2019 annual Canadian Community Health Survey, we analyzed the relationship between CRNA and moderate to severe depressive symptoms, assessed by the Patient Health Questionnaire (PHQ-9). Among the sample, 4.9% experienced CRNA and 6.8% experienced moderate to severe depressive symptoms. Respondents who reported CRNA had 1.51 (95% confidence interval [CI], 1.51-1.52) greater odds of experiencing moderate to severe depressive symptoms. Stratified analysis by sex and race showed the association between CRNA and depressive symptoms was greatest among racialized males (aOR: 1.83, 95% CI: 1.81- 1.85). Stratified analysis by sex and Indigeneity showed this association was greatest for Indigenous males (aOR: 2.16, 95% CI: 2.10-2.22). Forgoing prescribed medications due to cost is associated with more severe depressive symptoms among Canadians, particularly racialized and Indigenous males., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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.

Abstract: There are numerous, well-established racial disparities in the management of pain. The degree to which these are evident at the stage of conducting clinical trials is unknown. To address this knowledge gap, we examined race-based reporting, participation of Black individuals, and the factors associated with reporting and participation in pain clinical trials in the United States. Data were extracted from Clinicaltrials.gov and published articles. One thousand two hundred trials met our inclusion criteria; 482 (40.2%) reported participant race. More recent, publicly funded, and larger trials were more likely to report race. Of 82,468 participants included in pain clinical trials that reported race, 15,101 were Black individuals (18.3%). Participation of Black individuals was significantly associated with pain type (ß = +27% in cardiovascular disease pain compared with acute pain, P < 0.05), study population (ß = +33% and +7% in pain in minoritized populations and women, respectively, compared with general population, P < 0.05), pain intervention (ß = +7.5% for trials of opioid interventions compared with nonopioid interventions, P < 0.05), and a diverse team of investigators (ß = +8.0% for studies incorporating a visible non-White investigator compared with those that did not, P < 0.05). Our results indicate that representation of Black participants in pain clinical trials generally aligns with national demographics in the United States. Increased representation corresponds with health conditions more prevalent among Black individuals (eg, cardiovascular disease) and with a diverse study team composition. Despite these encouraging results, less than half of pain trials reported race, which introduces potential publication bias and limits external validity., (Copyright © 2023 International Association for the Study of Pain.)

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.)

Background: Asthma hospitalizations declined rapidly in many parts of the world, including Canada, in the 1990s and early 2000s., Objective: To examine whether the declining trend of asthma hospitalizations persisted in recent years in Canada., Methods: Using the Canadian comprehensive nationwide hospitalization data (2002-2017), we identified hospital admissions with the main International Classification of Diseases codes for asthma. We analyzed sex-specific age-standardized trends in annual hospitalization rates among pediatric (&lt; 19 years) and adult (19+ years) patients. We used change-point analysis to evaluate any substantial changes in the trends in the sex-age groups., Results: There were 254,672 asthma-related hospital admissions (59% pediatric, 50% female) during the study period. Among children, age-adjusted annual rates per 100,000 decreased by 55% in females (152-69) and by 60% in males (270-108) from 2002 to 2017. Among adults, the rates decreased by 59% in both sexes (females: 61-25; males: 27-11). Change-point analysis indicated a substantial plateauing of the annual rate in both pediatric (from -15.3 [females] and -25.8 [males] before 2010 to -0.6 [females] and -0.8 [males] after 2010) and adult (from -5.4 [females] and -2.6 [males] before 2008 to -0.6 [females] and -0.2 [males] after 2008) groups., Conclusion: After a substantial decline in hospital admissions for acute asthma, there has been minimal further decline since 2010 for children and 2008 for adults. In addition to adhering to the contemporary standards of asthma care, novel, disruptive strategies are likely needed to further reduce the burden of asthma., (Copyright © 2022 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

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).)

Objective: To determine whether sociodemographic and clinical factors were associated with nonelective readmission within 30 days of hospitalization for traumatic brain injury (TBI). Secondary objectives were to examine the effects of TBI severity on readmission and characterize primary reasons for readmission., Setting: Hospitalized patients in the United States, using the 2014 Nationwide Readmission Database., Participants: All patients hospitalized with a primary diagnosis of TBI between January 1, 2014, and November 30, 2014. We excluded patients (1) with a missing or invalid length of stay or admission date, (2) who were nonresidents, and 3) who died during their index hospitalization., Design: Observational study; cohort study., Main Measures: Survey weighting was used to compute national estimates of TBI hospitalization and nonelective 30-day readmission. Associations between sociodemographic and clinical factors with readmission were assessed using unconditional logistic regression with and without adjustment for suspected confounders., Results: There were 135 542 individuals who were hospitalized for TBI; 8.9% of patients were readmitted within 30 days of discharge. Age (strongest association for 65-74 years vs 18-24 years: adjusted odds ratio [AOR], 2.57; 95% CI: 2.02-3.27), documentation of a fall (AOR, 1.24; 95% CI: 1.13-1.35), and intentional self-injury (AOR, 3.13; 95% CI: 1.88-5.21) at the index admission were positively associated with readmission. Conversely, history of a motor vehicle (AOR, 0.69; 95% CI: 0.62-0.78) or cycling (AOR, 0.56; 95% CI: 0.40-0.77) accident was negatively associated with readmission. Females were also less likely to be readmitted following hospitalization for a TBI (AOR, 0.87; 95% CI: 0.82-0.92)., Conclusions: Many sociodemographic and clinical factors were found to be associated with acute readmission following hospitalizations for TBI. Future studies are needed to determine the extent to which readmissions following TBI hospitalizations are preventable., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

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.)

Background: In an attempt to aggregate observations from clinical trials, several meta-analyses have been published examining the effectiveness of systemic, non-opioid, pharmacological interventions to reduce the incidence of chronic postsurgical pain., Objective: To inform the design and reporting of future studies, the purpose of our study was to examine the quality of these meta-analyses., Evidence Review: We conducted an electronic literature search in Embase, MEDLINE, and the Cochrane Database of Systematic Reviews. Published meta-analyses, from the years 2010 to 2020, examining the effect of perioperative, systemic, non-opioid pharmacological treatments on the incidence of chronic postsurgical pain in adult patients were identified. Data extraction focused on methodological details. Meta-analysis quality was assessed using the A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2) critical appraisal tool., Findings: Our search yielded 17 published studies conducting 58 meta-analyses for gabapentinoids (gabapentin and pregabalin), ketamine, lidocaine, non-steroidal anti-inflammatory drugs, and mexiletine. According to AMSTAR 2, 88.2% of studies (or 15/17) were low or critically low in quality. The most common critical element missing was an analysis of publication bias. Trends indicated an improvement in quality over time and association with journal impact factor., Conclusions: With few individual trials adequately powered to detect treatment effects, meta-analyses play a crucial role in informing the perioperative management of chronic postsurgical pain. In light of this inherent value and despite a number of attempts, high-quality meta-analyses are still needed., Prospero Registration Number: CRD42021230941., Competing Interests: Competing interests: None declared., (© American Society of Regional Anesthesia & Pain Medicine 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

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).)

Purpose: In drug safety and effectiveness studies based on secondary data, the choice of an appropriate exposure measure for a given outcome can be challenging. Different measures of exposure can yield different estimates of treatment effect and safety. There is a knowledge gap with respect to developing and refining measures of drug exposure, to ensure that the exposure measure addresses the study question and is suitable for statistical analysis., Methods: We present a transparent, step-by-step approach to the development of drug exposure measures involving secondary data. This approach would be of interest to students and investigators with initial training in pharmacoepidemiology. We illustrate the approach using a study about Parkinson's disease., Results: We described the exposure specifications according to the study question. Next, we refined the exposure measure by linking it to knowledge about four major concepts in drug safety and effectiveness studies: drug use patterns, duration, timing, and dose. We then used this knowledge to guide the ultimate choice of exposure measure: time-varying, cumulative 6-month exposure to tamsulosin (a drug used to treat prostate hyperplasia)., Conclusions: The proposed approach links exposure specifications to four major concepts in drug safety and effectiveness studies. Formulating subject-matter knowledge about these major concepts provides an avenue to develop the rationale and specifications for the exposure measure., (© 2021 John Wiley & Sons Ltd.)

The cholinergic system is a complex neurotransmitter system with functional involvement at multiple levels of the nervous system including the cerebral cortex, spinal cord, autonomic nervous system, and neuromuscular junction. Anticholinergic medications are among the most prescribed medications, making up one-third to one-half of all medications prescribed for seniors. Recent evidence has linked long-term use of anticholinergic medications and dementia. Emerging evidence implicates the cholinergic system in the regulation of cerebral vasculature as well as neuroinflammation, suggesting that anticholinergic medications may contribute to absolute risk and progression of neurodegenerative diseases. In this review, we explore the involvement of the cholinergic system in various neurodegenerative diseases and the possible detrimental effects of anticholinergic medications on the onset and progression of these disorders. We identified references by searching the PubMed and Cochrane database between January 1990 and September 2019 for English-language animal and human studies including randomized clinical trials (RCTs), meta-analyses, systematic reviews, and observational studies. In addition, we conducted a manual search of reference lists from retrieved studies. Long-term anticholinergic medication exposure may have detrimental consequences beyond well-documented short-term cognitive effects, through a variety of mechanisms either directly impacting cholinergic neurotransmission or through receptors expressed on the vasculature or immune cells, providing a pathophysiological framework for complex interactions across the entire neuroaxis., (© 2020 International Society for Neurochemistry.)

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.

Introduction: The use of observational data to assess drug effectiveness and safety can provide relevant information, much of which may not be feasible to obtain through randomized clinical trials. Because observational studies provide critical drug safety and effectiveness information that influences drug policy and prescribing practices, transparent, consistent, and accurate reporting of these studies is critical., Areas Covered: We provide recommendations to extend existing reporting guidelines, covering the main components of primary research studies (methods, results, discussion)., Expert Opinion: Our recommendations include extending drug safety and effectiveness guidelines to include explicit checklist items on: study registration, causal diagrams, rationale for measures of effect, comprehensive assessment of bias, comprehensive data cleaning steps, drug equivalents, subject-level drug data visualization, sex and gender-based analyses and results, patient-oriented outcomes, and patient involvement in research.

Objective: To explore the hypothesis that earlier administration of acute gabapentinoids is beneficial to motor recovery after spinal cord injury in humans., Methods: This is an observational study using a cohort from the European Multi-Centre Study about Spinal Cord Injury. Patient charts were reviewed to extract information regarding the administration and timing of gabapentinoid anticonvulsants. The primary outcome measure was motor scores, as measured by the International Standards for Neurological Classification of Spinal Cord Injury, collected longitudinally in the first year after injury. Sensory scores (light touch and pinprick) and functional measures (Spinal Cord Independence Measure) were secondary outcomes. Linear mixed effects regression models included a drug-by-time interaction to determine whether exposure to gabapentinoids altered recovery of muscle strength in the first year after injury., Results: A total of 201 participants were included in the study and had a median age of 46 and baseline motor score of 50. Participants were mostly men (85%) with sensory and motor complete injuries (50%). Seventy individuals (35%) were administered gabapentinoids within the first 30 days after injury, and presented with similar demographics. In the longitudinal model, the administration of gabapentinoids within 30 days after injury was associated with improved motor recovery when compared to those who did not receive gabapentinoids during this time (3.69 additional motor points from 4 to 48 weeks after injury; p = 0.03). This effect size increased as administration occurred earlier after injury (i.e., a benefit of 4.68 points when administered within 5 days)., Conclusions: This retrospective, observational study provided evidence of the beneficial effect of gabapentinoid anticonvulsants on motor recovery after spinal cord injury. More critically, it highlighted a potential time dependence, suggesting that earlier intervention is associated with better outcomes., Classification of Evidence: This study provides Class IV evidence that gabapentinoids improve motor recovery for individuals with acute spinal cord injury., (© 2020 American Academy of Neurology.)

Background: In the context of the ongoing North American overdose crisis, a clear understanding of opioid prescription and usage trends is important. Although individuals with mood and/or anxiety disorders are a sub-population at increased risk of developing substance use disorders, they have been identified as more likely to receive opioid prescriptions. The primary objective of this study was to investigate differences in prescribed opioid-based pain reliever use between Canadians with and without diagnosed mood and/or anxiety disorders., Methods: We utilized data from the 2015-2016 Canadian Community Health Survey (CCHS), a population-based, cross-sectional survey. We examined self-reported diagnoses of mood and/or anxiety disorders and self-reported prescribed opioid-based pain reliever use. Logistic regression modeling was used to estimate the unadjusted and adjusted odds of prescribed opioid-based pain reliever use associated with mood and/or anxiety disorders., Results: Our study sample had 2,810 individuals. The prevalence of mood and/or anxiety disorders and prescribed opioid use was 11.7% and 14.6%, respectively. Individuals diagnosed with mood and/or anxiety disorders were more likely to use prescribed opioid-based pain relievers compared with individuals without these diagnoses (OR = 2.36, 95% CI = 1.64, 3.41), even after adjustment for age, sex, total household income, cultural/racial background, and chronic pain (AOR= 1.78, 95% CI= 1.23, 2.58)., Conclusions: Our findings suggest that mood and/or anxiety disorders were positively associated with prescribed opioid-based pain reliever use. Future research should investigate potential unmet healthcare needs among individuals with these conditions, as mood and/or anxiety disorders may be modifiable risk factors., (Copyright © 2020. Published by Elsevier B.V.)

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.)

Objective: To determine the population-level odds of individuals with spinal cord injury (SCI) experiencing fatigue and sleep apnea, to elucidate relationships with level and severity of injury, and to examine associations with abnormal cerebrovascular responsiveness., Methods: We used population-level data, meta-analyses, and primary physiologic assessments to provide a large-scale integrated assessment of sleep-related complications after SCI. Population-level and meta-analyses included more than 60,000 able-bodied individuals and more than 1,800 individuals with SCI. Physiologic assessments were completed on a homogenous sample of individuals with cervical SCI and matched controls. We examined the prevalence of (1) self-reported chronic fatigue, (2) clinically identified sleep apnea, and 3) cerebrovascular responsiveness to changing CO 2 ., Results: Logistic regression revealed a 7-fold elevated odds of chronic fatigue after SCI (odds ratio [OR] 7.9, 95% confidence interval [CI] 3.5-16.2), and that fatigue and trouble sleeping are correlated with the level and severity of injury. We further show that those with SCI experience elevated risk of clinically defined sleep-disordered breathing in more than 600 individuals with SCI (pooled OR 3.1, 95% CI 1.3-7.5). We confirmed that individuals with SCI experience a high rate of clinically defined sleep apnea using primary polysomnography assessments. We then provide evidence using syndromic analysis that sleep-disordered breathing is a factor strongly associated with impaired cerebrovascular responsiveness to CO 2 in patients with SCI., Conclusions: Individuals with SCI have an increased prevalence of sleep-disordered breathing, which may partially underpin their increased risk of stroke. There is thus a need to integrate sleep-related breathing examinations into routine care for individuals with SCI., (© 2019 American Academy of Neurology.)

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.

Background: Recent observational studies have shown an association between gabapentinoid anticonvulsants and greater motor recovery after spinal cord injury. There is preclinical evidence to suggest that other anticonvulsants, such as sodium channel blockers, may also confer beneficial effects., Purpose: The aim of the current study was to determine if non-gabapentinoid anticonvulsants were associated with neurological recovery after acute, traumatic spinal cord injury., Methods: This was an observational cohort study using data from the Sygen clinical trial. The primary outcome was total motor score recovery in the first year after injury. Anticonvulsant use was extracted from concomitant medication records; individuals were classified based on early administration (within 30 days of injury), or late/no administration. Motor recovery was compared using linear mixed effects regression models with a drug-by-time interaction, and adjustment for confounders. A secondary analysis incorporated a propensity score matched cohort., Results: Of the cohort (n = 570), 6% received anticonvulsants (carbamazepine, phenytoin, clonazepam, phenobarbital, and valproic acid) early after injury. After adjustments for initial injury level and severity, early exposure to non-gabapentinoid anticonvulsants was not associated with motor neurological outcomes (p = 0.38 for all anticonvulsants, p = 0.83 for sodium channel blockers, p = 0.82 in propensity-matched cohort)., Conclusion: Non-gabapentinoid anticonvulsant exposure was not associated with greater or lesser neurological recovery. This suggests that these medications, as administered for the acute management of spinal cord injury, do not impact long-term neurological outcomes.

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: Translational neuroscience is largely concerned with establishing causal links between biological processes and functional outcomes. Exciting new methods have emerged and top-tier biomedical journals are placing increasingly high demand for experiments that link outcomes. One pitfall to making these connections is the "ecological fallacy"-establishing a relationship between outcomes based on aggregate (averaged) results (a distinct issue from correlation vs causation)., Methods: To showcase the ecological fallacy, we first used simulated data to define and demonstrate the problem. Next, we performed a systematic review to determine the prevalence of the fallacy in top-tier biomedical journals (Science, Nature Medicine, Neuron, Nature, Nature Neuroscience, Cell). Based on our own research interests and specializations, we specifically focused on recent publications in the area of spinal cord injury and regenerative medicine., Results: Of the articles reviewed which examined a relationship between central nervous system regeneration and a behavioural outcome, 100% (21/21) were subject to possible ecological fallacy., Conclusions: Ecological fallacy is highly prevalent in neuroscience research and could partially account for translation failures in this field. Reporting guidelines for in vivo experiments should include subject-level correlation analyses for the primary outcomes., (© 2018 Stichting European Society for Clinical Investigation Journal Foundation.)

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: Amyotrophic lateral sclerosis (ALS) is a fatal degenerative neurological disease with significant effects on quality of life. International studies continue to provide consistent incidence values, though complete case ascertainment remains a challenge. The Canadian population has been understudied, and there are currently no quantitative data on the incidence of ALS in British Columbia (BC). The objectives of this study were to determine the five-year incidence rates of ALS in BC and to characterize the demographic patterns of the disease., Methods: The capture-recapture method was employed to estimate ALS incidence over a five-year period (2010-2015). Two sources were used to identify ALS cases: one database from an ALS medical centre and another from a not-for-profit ALS organization., Results: During this time period, there were 690 incident cases within the two sources. The capture-recapture method estimated 57 unobserved cases, corresponding to a crude five-year incidence rate of 3.29 cases per 100,000 (CI 95%=3.05-3.53). The mean age of diagnosis was 64.6 (CI 95%=59.7-69.4), with 63.5 (CI 95%=56.9-70.1) for men and 65.7 (CI 95%=58.6-72.7) for women. There was a slight male preponderance in incidence, with a 1.05:1 ratio to females. Peak numbers in incidence occurred between the ages of 70 and 79., Conclusions: The incidence of ALS in BC was found to be consistent with international findings though nominally higher than that in other Canadian provinces to date.