A Comparison of Neuropathic Pain Experiences Among Paralympic Versus Recreational Athletes with Spinal Cord Injury.

BACKGROUND: Individuals with spinal cord injury (SCI) report high levels of neuropathic pain. Current treatment options are primarily pharmaceutical, despite their limited effectiveness. Exercise may reduce neuropathic pain among persons with SCI; however, the optimal dose of exercise required to elicit analgesic effects remains unknown. The purpose of this study was to compare neuropathic pain intensity, pain catastrophizing, use of coping strategies, and positive affect and well-being among Paralympic versus recreational athletes with SCI who experience chronic neuropathic pain. Forty-seven athletes with SCI (25 Paralympic, 27 recreational) completed the International SCI Pain Basic Data Set, Douleur Neuropathique-4, coping strategies questionnaire, pain catastrophizing scale, and SCI-quality of life assessment. RESULTS: Paralympic athletes reported significantly greater neuropathic pain (p = 0.032) and positive affect and well-being (p = 0.047) than recreational athletes. No other comparisons were significant (ps > 0.09). Significant, medium-sized positive correlations were observed between neuropathic pain and total minutes of moderate-intensity exercise (r = 0.335, p = 0.023) and average minutes per day of moderate-intensity exercise (r = 0.375, p = 0.010) over the past week. CONCLUSIONS: The results suggest that frequent moderate- to high-intensity exercise may exacerbate neuropathic pain sensations for persons with SCI. Research should investigate psychosocial and physiological mechanisms by which exercise may influence neuropathic pain to explain how Paralympic athletes with SCI are able to continue exercising while maintaining positive affect despite neuropathic pain.

Theoretical components of smoking cessation interventions for persons with physical disabilities: A scoping review.

Rationale Persons with physical disabilities report higher cigarette smoking rates and a lower likelihood of accessing health services (e.g., smoking cessation services). Explicit and systematic application of behaviour change theory may be a promising approach to addressing these inequities and developing impactful smoking cessation interventions for persons with physical disabilities. OBJECTIVE: This scoping review aimed to explore how behaviour change theory and intervention components have been used to design smoking cessation interventions for persons with physical disabilities. METHODS: Electronic databases (Medline, Embase, PsycINFO, CINAHL, Web of Science) were systematically searched. Smoking cessation interventions for persons with physical disabilities were identified. Behaviour change theory and intervention components, including behaviour change techniques, intervention functions, mode of delivery, intervention source, and setting, were extracted from the included articles. RESULTS: Among the eleven included articles, there were nine unique smoking cessation interventions for persons with physical disabilities. Three interventions mentioned theory, but none of these articles explicitly applied or tested the theory. Intervention components were consistently combined to deliver pharmacotherapy and behavioural counselling-based interventions. CONCLUSION: The results of this review highlight the scarcity of theory-based smoking cessation interventions for persons with physical disabilities. While the interventions were not theory-based, they were evidence-based and aligned with recommendations for smoking cessation treatment (i.e., behavioural counselling plus pharmacotherapy). Future research should take a theory-based approach to intervention development to enhance the likelihood that smoking cessation interventions for persons with physical disabilities are effective, replicable, and equitable.

Modulation of myeloid and T cells in vivo by Bruton's tyrosine kinase inhibitor ibrutinib in patients with metastatic pancreatic ductal adenocarcinoma.

BACKGROUND: In preclinical studies of pancreatic ductal adenocarcinoma (PDAC), ibrutinib improved the antitumor efficacy of the standard of care chemotherapy. This led to a phase 1b clinical trial to determine the safety, tolerability, and immunologic effects of ibrutinib treatment in patients with advanced PDAC. METHODS: Previously untreated patients with PDAC were enrolled in a phase 1b clinical trial (ClinicalTrials.gov) to determine the safety, toxicity, and maximal tolerated dose of ibrutinib when administered with the standard regimen of gemcitabine and nab-paclitaxel. To study the immune response to ibrutinib alone, the trial included an immune response arm where patients were administered with ibrutinib daily for a week followed by ibrutinib combined with gemcitabine and nab-paclitaxel. Endoscopic ultrasonography-guided primary PDAC tumor biopsies and blood were collected before and after ibrutinib monotherapy. Changes in abundance and functional state of immune cells in the blood was evaluated by mass cytometry by time of flight and statistical scaffold analysis, while that in the local tumor microenvironment (TME) were assessed by multiplex immunohistochemistry. Changes in B-cell receptor and T-cell receptor repertoire were assessed by sequencing and analysis of clonality. RESULTS: In the blood, ibrutinib monotherapy significantly increased the frequencies of activated inducible T cell costimulator+(ICOS+) CD4+ T cells and monocytes. Within the TME, ibrutinib monotherapy led to a trend in decreased B-cell abundance but increased interleukin-10+ B-cell frequency. Monotherapy also led to a trend in increased mature CD208+dendritic cell density, increased late effector (programmed cell death protein 1 (PD-1-) eomesodermin (EOMES+)) CD8+ T-cell frequency, with a concomitantly decreased dysfunctional (PD-1+ EOMES+) CD8+ T-cell frequency. When ibrutinib was combined with chemotherapy, most of these immune changes were not observed. Patients with partial clinical responses had more diverse T and B cell receptor repertoires prior to therapy initiation. CONCLUSION: Ibrutinib monotherapy skewed the immune landscape both in the circulation and TME towards activated T cells, monocytes and DCs. These effects were not observed when combining ibrutinib with standard of care chemotherapy. Future studies may focus on other therapeutic combinations that augment the immunomodulatory effects of ibrutinib in solid tumors. TRIAL REGISTRATION NUMBER: NCT02562898.

Acute submaximal exercise does not impact aspects of cognition and BDNF in people with spinal cord injury: A pilot study.

Objective: To investigate the effect of acute submaximal exercise, based on the spinal cord injury (SCI) Exercise Guidelines, on cognition and brain-derived neurotrophic factor (BDNF) in people with SCI. Design: Eight adults (7 males) with traumatic SCI volunteered in this pre-registered pilot study. In randomized order, participants completed submaximal intensity arm cycling (60% of measured peak-power output at 55-60 rpm) for 30 min or time-matched quiet rest (control condition) on separate days. Blood-borne BDNF was measured in serum and plasma at pre-intervention, 0 min and 90 min post-intervention. Cognition was assessed using the Stroop Test and Task-Switching Test on an electronic tablet pre- and 10 min post-intervention. Results: Submaximal exercise had no effect on plasma [F(2,12) = 1.09; P = 0.365; η² = 0.069] or serum BDNF [F(2,12) = 0.507; P = 0.614; η² = 0.024] at either 0 min or 90 min post-intervention. Similarly, there was no impact of exercise on either Stroop [F(1,7) = 2.05; P = 0.195; η² = 0.065] or Task-Switching performance [F(1,7) = 0.016; P = 0.903; η² < 0.001] compared to the control condition. Interestingly, there was a positive correlation between years since injury and resting levels of both plasma (r = 0.831; P = 0.011) and serum BDNF (r = 0.799; P = 0.023). However, there was not relationship between years since injury and the BDNF response to exercise. Conclusions: Acute guideline-based exercise did not increase BDNF or improve aspects of cognition in persons with SCI. This work establishes a foundation for continued investigations of exercise as a therapeutic approach to promoting brain health among persons with SCI.

Impact of an Acute Bout of Submaximal Aerobic Exercise on Circulating Leukocytes in Individuals with Spinal Cord Injury.

Individuals with spinal cord injury (SCI) may experience cardiovascular, musculoskeletal and organ function dysregulation. Sequelae include reduced catecholamine secretion and attenuated immune responses which may impact exercise-induced leukocytosis. The purpose of this study was to characterize major leukocyte subtypes following 30 minutes of acute, submaximal aerobic exercise, in line with updated international SCI exercise guidelines for adults. It was hypothesized that exercise would increase major leukocyte subtypes when compared to fasted baseline. Eight participants with SCI (incomplete n = 6; complete n = 2) completed a 30-minute bout of aerobic exercise on an arm cycle ergometer at 60% of their peak power output followed by 90 minutes of recovery, or a 2-hour seated control condition, in a randomized crossover design, separated by 7-14 days. Blood samples were taken at baseline, post exercise, and 90 minutes after exercise (with time matched control). Leukocyte subtypes were analyzed via flow cytometry and plasma catecholamines by ELISA. Several leukocytes increased from pre- to post-exercise (time X condition interaction; all P < 0.05; mean ± SD), including CD3+ Lymphocytes (19 ± 16%), CD4+ T helper (16 ± 13%), CD8+ T cytotoxic (24 ± 23%), CD3+/CD56+ natural killer T (31 ± 34%), and CD3-/CD56+ natural killer (63 ± 82%). CD16+/CD14dim monocytes decreased by 27 ± 38% following exercise to 90 minutes post-exercise. No changes were observed for catecholamines for either condition. Thirty minutes of acute submaximal aerobic exercise sufficiently increased most lymphocyte subsets with effector functions, while leading to decreased proinflammatory monocytes during the recovery phase. This exercise duration and intensity appear to be an appropriate option for modulating circulating immune cells in individuals with SCI.

The effects of a high-fat/high-carbohydrate meal on leukocyte populations in adults with chronic spinal cord injury.

STUDY DESIGN: Secondary analysis of aggregated case series data. OBJECTIVES: To examine the effects of a high-fat/high-carbohydrate meal on leukocyte populations in adults with a chronic SCI. SETTING: University-based laboratories in British Columbia, Canada. METHODS: Ten individuals (M = 9) with a traumatic SCI (>1-year post-injury; M = 15.5 years; n = 2 sensory complete, n = 7 motor complete) participated in this study. Participants arrived fasted (≥12 h) prior to both the control (quiet sitting, no food/drink) and experimental meal conditions (high-fat/high-carb meal: 880 kcal, 52 g fat, 73 g carbohydrates, 29 g protein). Blood samples were taken in the fasted state and at 120-min post-meal/baseline in both conditions. Immune cell counts were assessed using multi-color flow cytometry. RESULTS: A significant time × condition interaction effect was seen in CD3+, CD4+, and CD8+ T cells as well as CD56+ and CD3+/CD56+ natural killer (NK) cells (p < 0.05). CD14+/CD16+ monocytes and CD19+ B cells approached a significant time × condition interaction (p < 0.07). A main effect of time was observed in CD19+ B cells (p < 0.05). Cell counts for T-lymphocytes and NK cells followed the general trend of an increase in the control condition from baseline to 120-min with no change observed following the experimental meal condition. CONCLUSIONS: Following the HFHC meal, immune cells did not show the same general increase observed following the control condition. Future research is needed to determine if there are any potential consequences of these immune cell responses in immunosuppressed populations and if other factors (e.g., diurnal variation) might influence immune cell response.

Using ecological momentary assessment to evaluate neuropathic pain experienced by adults with SCI: recommendations and participant perceptions.

PURPOSE: Neuropathic pain is a debilitating consequence of spinal cord injury. Ecological momentary assessment can be a valuable research tool for understanding temporal fluctuations in neuropathic pain and designing effective management strategies. The objectives of this study were to (a) describe strategies necessary to adapt ecological momentary assessment to measure neuropathic pain in adults with spinal cord injury, and (b) explore participant perceptions of using ecological momentary assessment to measure pain sensations. METHODS: End-users with spinal cord injury provided input to guide development of an ecological momentary assessment protocol. Six adults with spinal cord injury (ages 27-50 years, M = 39.33 ± 8.24) engaged in the six-day protocol and completed six daily neuropathic pain assessments. Upon finishing participants completed a semi-structured interview regarding their protocol experiences. A qualitative content analysis was used to analyze the interview data. RESULTS: Participants reported that this specific ecological momentary assessment protocol was unobtrusive to their daily routines, and effectively captured their neuropathic pain sensations. However, participants experienced increased neuropathic pain due to the repeated nature of assessments. CONCLUSION: Ecological momentary assessment can capture the dynamic nature of neuropathic pain experienced by persons with spinal cord injury. However, caution should be taken when designing intensive pain-related protocols to minimize pain exacerbation.IMPLICATIONS FOR REHABILITATIONNeuropathic pain affects up to 75% of people with spinal cord injury and is one of the most frequently occurring, debilitating forms of pain.Appropriate and feasible pain data collection methods are necessary to acquire a better understanding of how neuropathic pain manifests in people with spinal cord injury.Implementing ecological momentary assessment in a rehabilitation setting may help facilitate the monitoring of neuropathic pain for both rehabilitation professionals and persons with SCI.Using ecological momentary assessment may lead to a better understanding of individual temporal patterns of neuropathic pain that could inform the design of tailored neuropathic pain management techniques.

The Impact of Sub-maximal Exercise on Neuropathic Pain, Inflammation, and Affect Among Adults With Spinal Cord Injury: A Pilot Study.

Introduction: Persons with spinal cord injury (SCI) often report high levels of neuropathic pain (NP) and poor well-being, which may result from increased inflammation. This study examined the impact of sub-maximal aerobic exercise on NP, inflammation and psychological affect among adults with SCI. Methods: Eight active adults with tetraplegia (n-4, AIS A-C) and paraplegia (n = 4, AIS A-C) performed 30-min of arm-crank aerobic exercise and reported their ratings of perceived exertion (RPE) each minute. Measures of NP, affect, and inflammatory cytokines (IL-6, IL-10, IL-1ra, TNF-α) were taken pre-(T0), immediately post-(T1), and 90-min post-exercise (T2). Results: NP decreased between T0 and T1 for tetraplegics (-60%, d = 0.47; CI = -0.32, 2.02) and paraplegics (-16%, d = 0.15; CI = -0.30, 0.90). Correlations between change in cytokines and change in NP were medium-to large for tetraplegics (rs ranged from -0.820 to 0.965) and paraplegics (rs ranged from -0.598 to 0.833). However, the pattern of correlations between change in cytokines and affect was inconsistent between groups. Lower baseline levels of IL-1ra predicted greater decreases in NP immediately post-exercise (r = 0.83, p = 0.01). Conclusion: Sub-maximal exercise can positively impact NP for some persons with SCI. Further experimental research should identify the optimal exercise intensity to reduce NP for persons with SCI, in addition to understanding biomarkers which may predict changes in NP. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT03955523.

A Scoping Review of Peer Mentorship Studies for People with Disabilities: Exploring Interaction Modality and Frequency of Interaction.

Given our understanding of the importance of peer mentorship for people with disabilities, research needs to begin exploring characteristics of the mentor-mentee relationship that could contribute to the observed positive outcomes. To date, no review has examined characteristics of peer mentorship (i.e. interaction modality, interaction frequency) that could impact the quality and effectiveness of this service. The primary purpose was to synthesize the peer-reviewed peer mentorship literature for people with disabilities and report on the interaction modality and frequency employed in each study. A secondary purpose was to document the results of studies that have tested relationships between the outcomes of peer mentorship and interaction modality or frequency. A scoping review was performed that involved a systematic search of MEDLINE, EMBASE, PsychINFO, CINAHL, Web of Science, and SPORTDiscus. Thirteen studies met the inclusion criteria. Articles reported five different interaction modalities; the telephone (n = 12) was the most common. Frequency of interactions was reported in nine studies with mentees reporting between 3 and 77 interactions with their mentor. Only one study attempted to analyze the mediating or moderating effects of modality and frequency on the reported outcomes. In conclusion, peer mentorship is occurring through various interaction modalities and at varying frequencies. Future research should focus on examining the impact that modality and frequency of interaction have on outcomes of peer mentorship.

Physical activity interventions, chronic pain, and subjective well-being among persons with spinal cord injury: a systematic scoping review.

STUDY DESIGN: Scoping review of experimental and quasi-experimental studies. OBJECTIVE: To systematically synthesize research testing the effects of leisure time physical activity (LTPA) interventions on chronic pain and subjective well-being (SWB) among adults with spinal cord injury (SCI). METHODS: Literature searches were conducted using multiple databases (Web of Science, Embase, CINAHL, Medline, PsychINFO and SPORTDiscus) to identify studies involving persons with SCI that measured and reported the effects of LTPA interventions on both chronic pain and at least one measure of SWB (e.g., affect, life satisfaction, satisfaction with various life domains). Relevant data were extracted from the studies and synthesized. RESULTS: A total of 3494 articles were screened. Fifteen published articles, consisting of 12 different studies met the review inclusion criteria. Four different patterns of findings were observed regarding the effect of LTPA on chronic pain and SWB outcomes: (1) increased chronic pain, decreased SWB (1 article); (2) decreased chronic pain, improved SWB (12 articles); (3) increased chronic pain, improved SWB (1 article); and (4) unchanged levels of pain, improved SWB (1 article). CONCLUSIONS: Results of most articles included in this scoping review suggest that LTPA interventions can reduce chronic pain and improve SWB for persons with SCI. Further research is needed to identify the mechanisms by which LTPA affects pain and SWB, in order to formulate LTPA prescriptions that maximize improvements in these outcomes.

Correction: A pragmatic randomized controlled trial testing the effects of the international scientific SCI exercise guidelines on SCI chronic pain: protocol for the EPIC-SCI trial.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

A pragmatic randomized controlled trial testing the effects of the international scientific SCI exercise guidelines on SCI chronic pain: protocol for the EPIC-SCI trial.

STUDY DESIGN: Protocol for a pragmatic randomized controlled trial (the Exercise guideline Promotion and Implementation in Chronic SCI [EPIC-SCI] Trial). PRIMARY OBJECTIVES: To test if home-/community-based exercise, prescribed according to the international SCI exercise guidelines, significantly reduces chronic bodily pain in adults with SCI. SECONDARY OBJECTIVES: To investigate: (1) the effects of exercise on musculoskeletal and neuropathic chronic pain; (2) if reduced inflammation and increased descending inhibitory control are viable pathways by which exercise reduces pain; (3) the effects of chronic pain reductions on subjective well-being; and (4) efficiency of a home-/community-based exercise intervention. SETTING: Exercise in home-/community-based settings; assessments in university-based laboratories in British Columbia, Canada. METHOD: Eighty-four adults with chronic SCI, reporting chronic musculoskeletal or neuropathic pain, and not meeting the current SCI exercise guidelines, will be recruited and randomized to a 6-month Exercise or Wait-List Control condition. Exercise will occur in home/community settings and will be supported through behavioral counseling. All measures will be taken at baseline, 3-months and 6-months. Analyses will consist of linear mixed effect models, multiple regression analyses and a cost-utility analysis. The economic evaluation will examine the incremental costs and health benefits generated by the intervention compared with usual care. ETHICS AND DISSEMINATION: The University of British Columbia Clinical Research Ethics Board approved the protocol (#H19-01650). Using an integrated knowledge translation approach, stakeholders will be engaged throughout the trial and will co-create and disseminate evidence-based recommendations and messages regarding the use of exercise to manage SCI chronic pain.

Physical activity among individuals with spinal cord injury who ambulate: a systematic scoping review.

STUDY DESIGN: Systematic scoping review. OBJECTIVES: The purpose of this project was to conduct a scoping review to understand the amounts, types, correlates, and outcomes of physical activity (PA) participation for ambulators with SCI. METHODS: A systematic search was employed among five large databases and two theses/dissertation databases, yielding 3257 articles. Following a two-phase screening process by independent coders, 17 articles were included in the review. Data were charted and summarized, and correlates were coded using the COM-B model. RESULTS: 11 studies were cross-sectional, 5 studies involved an exercise intervention, and 1 study used mixed methods. Overall, ambulators with SCI participated in low levels of PA. The type of PA investigated across all studies was leisure-time PA (e.g., sports, exercise). Psychological and physical capability (e.g., perceived behavioral control, fatigue), social and environmental opportunity (e.g., perceptions of disability, cost), and automatic and reflective motivation (e.g., boredom, intentions) were correlates of PA measured within studies. Exercise intervention studies measured physical (e.g., strength, fitness) and one psychological outcome (i.e., depression). No studies examined the quality of PA experiences. CONCLUSIONS: Only leisure-time PA has been investigated among ambulators with SCI, and low levels of leisure-time PA have been reported. Correlates of leisure-time PA can be mapped onto all COM-B model constructs and are potential targets for PA-enhancing interventions. Further investigation is warranted into the physical and psychosocial outcomes across all types of LTPA in addition to understanding the quality of LTPA experiences.

Co-development of a physiotherapist-delivered physical activity intervention for adults with spinal cord injury.

STUDY DESIGNS: Cross-sectional survey, semi-structured interview, and randomized-controlled trial. OBJECTIVES: Optimal spinal cord injury (SCI)-specific PA intervention strategies appropriate for the physiotherapist setting are unknown. The purpose of this paper is to describe the rigorous co-development process of a theory-based, physiotherapist-led PA intervention for people with SCI and assess its feasibility for implementation in the rehabilitation setting. SETTING: Community. METHODS: Co-development of the intervention included (1) a review of the literature; (2) key informant interviews with people with SCI (n = 26); (3) a national online survey of physiotherapists' barriers, needs, and preferences (n = 239); (4) a review of the evidence and recommendations for the intervention from a stakeholder expert panel (n = 13); and (5) a randomized controlled trial of intervention training and its effects on implementation determinants amongst physiotherapists (n = 20). RESULTS: Almost 300 people with SCI and physiotherapists were engaged in the intervention development process. Optimal intervention delivery should be tailored and include (1) education on safety, PA guidelines, and behaviour change techniques, (2) referral to other peers, local programmes, and health professionals, and (3) adapted exercise prescriptions. Following intervention implementation training, physiotherapists demonstrated stronger tested and perceived knowledge, skills, resources, and confidence for promoting PA to people with SCI, ps < 0.05. CONCLUSIONS: This development process serves as an example methodology for using theory to co-create a leisure-time physical activity behaviour change intervention tailored for people with SCI.

A Phase II Study Alternating Erlotinib With Second-line mFOLFOX6 or FOLFIRI for Metastatic Colorectal Cancer.

BACKGROUND: Based on our pre-clinical data, we hypothesized that sequencing chemotherapy with erlotinib would increase the tumor response rate in patients with metastatic colorectal cancer. PATIENTS AND METHODS: A phase II trial (planned n=58) using second-line therapy for metastatic colorectal cancer with either oxaliplatin-based (mFOLFOX6) or irinotecan-based (FOLFIRI) combination chemotherapy and 100 mg erlotinib daily on days 3-8 after each infusion (days 1 and 2) every 14 days. The primary endpoint was the response rate compared to the historical response rate. RESULTS: The FOLFIRI/erlotinib arm met the pre-specified response rate criteria of at least 10% to expand accrual to the intended sample size. The trial was halted after an interim safety analysis (n=11) due to excess grade 3 neutropenia, dose reductions and treatment delays. Grade 3 or 4 neutropenia was observed in 64% of patients. The response rate was 18%. CONCLUSION: In second-line treatment for metastatic colorectal cancer, mFOLFOX6 or FOLFIRI with erlotinib in a sequence-dependent fashion is not feasible despite potential promising activity.

An examination of diurnal variations in neuropathic pain and affect, on exercise and non-exercise days, in adults with spinal cord injury.

STUDY DESIGN: Case series. OBJECTIVES: The temporal relationships between exercise, neuropathic pain and affect are not well understood. The purpose of this study was to utilize ecological momentary assessment to measure intra-individual diurnal variations in neuropathic pain and affect on exercise and non-exercise days. This study aimed to provide a deeper understanding of how neuropathic pain and affect change from pre- to post-exercise, and over time. SETTING: Community. METHODS: Six physically active men with SCI participated in a 6-day protocol (M age = 39.33 ± 8.24; 83.3% tetraplegics; years post injury = 6-17 years). Using their Smartphones, participants completed the Feeling Scale, Felt Arousal Scale, and Neuropathic Pain Scale in response to six daily prompts, and before and after exercise. Paired samples t-tests were conducted on changes in neuropathic pain and affect from pre to post-exercise. Bivariate Pearson's correlational analyses were computed between time of day, neuropathic pain and affect. RESULTS: Participants experienced a significant decrease in neuropathic pain (t(5) = 3.93; p = 0.01) following completion of at least one bout of exercise. A large, but non-significant increase (Hgav = 0.76) in Feeling Scale scores occurred following one bout of exercise. Time of day, neuropathic pain and affect were significantly correlated for two participants. CONCLUSIONS: Overall, results suggest exercise can reduce neuropathic pain, and may also increase feelings of pleasure. Given the inconsistent pattern of results across participants, further research is needed to look at both individual characteristics, and characteristics of exercise that may moderate changes in neuropathic pain and affect for adults with SCI.