bluuebunny/crossref_metadata_2025_split huggingface dataset:
Using a Prism Paradigm to Identify Sensorimotor Impairment in Youth Following Concussion
Authors: Little C. Elaine , Dukelow Sean P. , Schneider Kathryn J. , Emery Carolyn A. 
Published: June 2021

Objective:
The study assesses the intrarater reliability and utility of a prism paradigm to identify sensorimotor impairment following sports-related concussion in youth, (recent and history of concussion) compared with youth with no concussion.

Setting:
University of Calgary.

Participants:
Three groups of 40 ice hockey players ranging in age from 11 to 17 years were included: (1) no concussion; (2) recent concussion, mean number of days since last concussion 5 (95% CI, 4-6); and (3) history of concussion, mean number of days since last concussion 631 (95% CI, 505-730).

Design:
Cross-sectional study.

Main Measures:
The vestibulo-ocular reflex is a fundamental reflex of the central nervous system that stabilizes the position of the eyes during head movement and adapts when sensory input is altered (the bend of the light on the retina by prism glasses). The prism adaptation measure was the number of throws taken to adapt to wearing prism glasses while throwing balls at a central target.

Results:
The intraclass correlation coefficient (0.73; 95% CI, 0.55-0.84) and the Bland-Altman 95% levels of agreement (lower limit −18.5; 95% CI, −22.4 to −14.6); and upper limit 16.6; 95% CI, 12.7-20.5) reflected good intrarater reliability. Prism adaptation measures were significantly different across groups (F
2,119 = 51.9, P < .001, r = 0.52, power of 90%), with the mean number of throws for youth (aged 11-17 years) in each group as follows: 10 (95% CI, 8-12) no concussion history; 25 (95% CI, 23-27) recent concussion (1-11 days); and 17 (95% CI, 15-20) history of concussion (90-1560 days).

Conclusion:
Use of a prism paradigm as a clinical measurement tool has the potential to alter concussion management in youth. The prism paradigm is objective, is readily translatable to the clinical arena, has minimal associated costs, and is easily administered, reliable, and portable.
Progressive Neurodegeneration Across Chronic Stages of Severe Traumatic Brain Injury
Authors: Belchev Zorry , Gilboa Asaf , Binns Malcolm , Colella Brenda , Glazer Joanna , Mikulis David J. , Green Robin E. 
Published: June 2021

Objective:
To examine the trajectory of structural gray matter changes across 2 chronic periods of recovery in individuals who have sustained severe traumatic brain injury (TBI), adding to the growing literature indicating that neurodegenerative processes occur in the months to years postinjury.

Participants:
Patients who experienced posttraumatic amnesia of 1 hour or more, and/or scored 12 or less on the Glasgow Coma Scale at the emergency department or the scene of the accident, and/or had positive brain imaging findings were recruited while receiving inpatient care, resulting in 51 patients with severe TBI.

Methods:
Secondary analyses of gray matter changes across approximately 5 months, 1 year, and 2.5 years postinjury were undertaken, using an automated segmentation protocol with improved accuracy in populations with morphological anomalies. We compared patients and matched controls on regions implicated in poorer long-term clinical outcome (accumbens, amygdala, brainstem, hippocampus, thalamus). To model brain-wide patterns of change, we then conducted an exploratory principal component analysis (PCA) on the linear slopes of all regional volumes across the 3 time points. Finally, we assessed nonlinear trends across earlier (5 months-1 year) versus later (1-2.5 years) time-windows with PCA to compare degeneration rates across time. Chronic degeneration was predicted cortically and subcortically brain-wide, and within specific regions of interest.

Results:
(1) From 5 months to 1 year, patients showed significant degeneration in the accumbens, and marginal degeneration in the amygdala, brainstem, thalamus, and the left hippocampus when examined unilaterally, compared with controls. (2) PCA components representing subcortical and temporal regions, and regions from the basal ganglia, significantly differed from controls in the first time-window. (3) Progression occurred at the same rate across both time-windows, suggesting neither escalation nor attenuation of degeneration across time.

Conclusion:
Localized yet progressive decline emphasizes the necessity of developing interventions to offset degeneration and improve long-term functioning.
Perceived Injustice After Mild Traumatic Brain Injury
Authors: Mäki Kaisa , Nybo Taina , Hietanen Marja , Huovinen Antti , Marinkovic Ivan , Isokuortti Harri , Melkas Susanna 
Published: June 2021

Objective:
To examine perceived injustice and its associations with self-reported symptoms and return to work at 3 months after injury in a prospectively recruited sample of patients with mild traumatic brain injury (mTBI).

Design:
Observational study.

Setting:
TBI outpatient unit.

Participants:
Adult patients aged 18 to 68 years with mTBI (n = 100) or orthopedic injury ([OI]; n = 34).

Main Measures:
The Injustice Experience Questionnaire (IEQ) and its associations with the Rivermead Post Concussion Questionnaire (RPQ), Beck Depression Inventory–Second Edition (BDI-II), PTSD Checklist–Civilian Version (PCL-C), and Pain Visual Analog Scale (PVAS). Information on injury-related characteristics, compensation seeking and litigation, and return-to-work status was also collected.

Results:
Median IEQ total score was 3 (range, 0-23) in the mTBI group and 2.5 (range, 0-25) in the OI group. In the mTBI group, IEQ was significantly correlated with RPQ (r
s = 0.638, P < .01), BDI-II (r
s = 0.612, P < .01), PCL-C (r
s = 0.679, P < .01), and PVAS (r
s = 0.232, P < .05). The association between IEQ and PCL-C (r
s =0.797, P < .01) and BDI-II (r
s = 0.395, P < .05) was also found in the OI group. In both groups, patients who were still on sick leave at 3 months after injury tended to report higher perceived injustice (IEQ total score) than patients who had returned to work or studies. However, this difference did not reach statistical significance.

Conclusions:
Perceived injustice is associated with self-reported symptoms in patients with mTBI. Our results suggest that perceived injustice could be a relevant construct to consider in clinical management of patients with mTBI. Also, perceived injustice could be a potential target for psychological interventions promoting recovery after mTBI.
Contributions of PCSS, BESS, Tandem Gait, and Romberg Test for Identifying Balance Deficits in Pediatric Concussions
Authors: Patel Rishi D. , LaBella Cynthia R. 
Published: June 2021

Objective:
Balance deficits are common after concussions in pediatric patients. This study evaluates 3 clinical tools for identifying postconcussion balance deficits in a pediatric population: (1) Post-Concussion Symptom Scale (PCSS); (2) Balance Error Scoring System (BESS); and (3) physical examination measures of balance: tandem gait (TG) and Romberg test.

Setting:
Data were collected in a tertiary care outpatient pediatric sports medicine clinic.

Participants:
English-speaking patients aged 8 to 17 years who presented to a tertiary care hospital-based pediatric sports medicine clinic and diagnosed with concussion between August 2014 and February 2018 were invited to participate. A total of 614 patients were screened and/or approached during the inclusion period and 500 were enrolled. Of those enrolled, 423 patients had complete data collected and analyzed.

Design:
This is a cross-sectional, observational data set from a longitudinal, prospective study.

Main Measures:
Data extracted from patients' electronic medical records included physical examination, PCSS, and BESS scores from their initial visit. Descriptive statistics were calculated for the outcome measures. A logistic regression was performed to evaluate significant contributors to abnormal BESS score (≥25).

Results:
There were 423 patients (56.7% female; 14.7 ± 2.01 years old) included in the study. Overall, we identified 336 patients (79.4%) with balance difficulties. Of the 336 with balance difficulties, 284 (84.5%) reported “balance problems” and/or “dizziness” on PCSS, 153 (45.5%) had abnormal BESS scores (≥25), and 100 (29.8%) had an abnormality on either TG or Romberg test.

Conclusion:
Balance difficulties were identified in close to 80% of children with concussions. Using PCSS and BESS along with physical examination measures, TG and Romberg test, identified more patients with balance deficits than using TG and Romberg test alone.
Piezo2 mechanosensitive ion channel is located to sensory neurons and nonneuronal cells in rat peripheral sensory pathway: implications in pain
Authors: Shin Seung Min , Moehring Francie , Itson-Zoske Brandon , Fan Fan , Stucky Cheryl L. , Hogan Quinn H. , Yu Hongwei 
Published: June 2021

Abstract
Piezo2 mechanotransduction channel is a crucial mediator of sensory neurons for sensing and transducing touch, vibration, and proprioception. We here characterized Piezo2 expression and cell specificity in rat peripheral sensory pathway using a validated Piezo2 antibody. Immunohistochemistry using this antibody revealed Piezo2 expression in pan primary sensory neurons of dorsal root ganglia in naïve rats, which was actively transported along afferent axons to both central presynaptic terminals innervating the spinal dorsal horn (DH) and peripheral afferent terminals in the skin. Piezo2 immunoreactivity (IR) was also detected in the postsynaptic neurons of the DH and in the motor neurons of the ventral horn, but not in spinal glial fibrillary acidic protein–positive and Iba1-positive glia. Notably, Piezo2-IR was clearly identified in peripheral nonneuronal cells, including perineuronal glia, Schwann cells in the sciatic nerve and surrounding cutaneous afferent endings, as well as in skin epidermal Merkel cells and melanocytes. Immunoblots showed increased Piezo2 in dorsal root ganglia ipsilateral to plantar injection of complete Freund's adjuvant, and immunostaining revealed increased Piezo2-IR intensity in the DH ipsilateral to complete Freund's adjuvant injection. This elevation of DH Piezo2-IR was also evident in various neuropathic pain models and monosodium iodoacetate knee osteoarthritis pain model, compared with controls. We conclude that (1) the pan neuronal profile of Piezo2 expression suggests that Piezo2 may function extend beyond simply touch or proprioception mediated by large-sized low-threshold mechanosensitive primary sensory neurons; (2) Piezo2 may have functional roles involving sensory processing in the spinal cord, Schwann cells, and skin melanocytes; and (3) aberrant Piezo2 expression may contribute pain pathogenesis.
Postinjury stimulation triggers a transition to nociplastic pain in mice
Authors: Hankerd Kali , McDonough Kathleen E. , Wang Jigong , Tang Shao-Jun , Chung Jin Mo , La Jun-Ho 
Published: June 2021

Abstract
Acute injury–induced pain can transition to chronic nociplastic pain, which predominantly affects women. To facilitate studies on the underlying mechanisms of nociplastic pain, we developed a mouse model in which postinjury thermal stimulation (intermittent 40°C water immersion for 10 minutes at 2 hours postcapsaicin) prolongs capsaicin (ie, experimental injury)-induced transient mechanical hypersensitivity outside of the injury area. Although capsaicin injection alone induced mechanical and thermal hypersensitivity that resolved in ∼7 days (slower recovery in females), the postinjury stimulation prolonged capsaicin-induced mechanical, but not thermal, hypersensitivity up to 3 weeks in both sexes. When postinjury stimulation was given at a lower intensity (30°C) or at later time points (40°C at 1-3 days postcapsaicin), chronification of mechanical hypersensitivity occurred only in females. Similar chronification could be induced by a different postinjury stimulation modality (vibration of paw) or with a different injury model (plantar incision). Notably, the 40°C postinjury stimulation did not prolong capsaicin-induced inflammation in the hind paw, indicating that the prolonged mechanical hypersensitivity in these mice arises without clear evidence of ongoing injury, reflecting nociplastic pain. Although morphine and gabapentin effectively alleviated this persistent mechanical hypersensitivity in both sexes, sexually dimorphic mechanisms mediated the hypersensitivity. Specifically, ongoing afferent activity at the previously capsaicin-injected area was critical in females, whereas activated spinal microglia were crucial in males. These results demonstrate that postinjury stimulation of the injured area can trigger the transition from transient pain to nociplastic pain more readily in females, and sex-dependent mechanisms maintain the nociplastic pain state.
Evaluation of the effect of analgesic treatment on signs of nociception-related behaviors during physiotherapy in patients with disorders of consciousness: a pilot crossover randomized controlled trial
Authors: Bonin Estelle A.C. , Binda Fossati Mariachiara L. , Filippini Maria M. , Bornheim Stephen , Lejeune Nicolas , O'Brien Anthony T. , Bodart Olivier , Laureys Steven , Thibaut Aurore , Chatelle Camille 
Published: June 2021

Abstract
Neuro-orthopedic disorders are common in patients with disorders of consciousness (DOC) and can lead to potential pain. However, the patients' inability to communicate makes pain detection and management very challenging for clinicians. In this crossover randomized double-blind placebo-controlled study, we investigated the effects of an analgesic treatment on the presence of nociception-related behaviors. At baseline, the Nociception Coma Scale-Revised (NCS-R) was performed in 3 conditions: a non-noxious stimulation, a noxious stimulation, and during a physiotherapy session. Patients with a NCS-R total score during physiotherapy equal or above the score observed after the noxious stimulation could participate to the clinical trial, as well as patients with a score above 5. They received an analgesic treatment and a placebo on 2 consecutive days in a randomized order followed by an assessment with the NCS-R. Of the 18 patients, 15 displayed signs of potential pain during physiotherapy. Patients showed higher NCS-R scores during physiotherapy compared with the other conditions, suggesting that mobilizations were potentially painful. Of these 15 patients, 10 met the criteria to participate in the placebo-controlled trial. We did not find any effect of analgesic treatment on the NCS-R scores. This study highlights that physiotherapy may be potentially painful for patients with DOC, while analgesic treatments did not reduced NCS-R scores. Therefore, careful monitoring with appropriate assessment and treatment before and during mobilization should become a priority in clinical settings. Future studies should focus on the development of assessment tools sensitive to analgesic dosage to manage pain in DOC.
Within-day rhythms of pain and cognitive function in people with and without fibromyalgia: synchronous or syncopated?
Authors: Whibley Daniel , Williams David A. , Clauw Daniel J. , Sliwinski Martin J. , Kratz Anna L. 
Published: June 2021

Abstract
Cognitive dysfunction is a common fibromyalgia (FM) symptom and can impact on the daily lives of those affected. We investigated whether within-day pain intensity ratings were associated with contemporaneous objective and subjective measures of cognitive function and whether within-day increases in pain intensity preceded increases in cognitive dysfunction or vice versa. Inclusion of a non-FM group allowed us to examine whether effects were specific to FM. Fifty people with FM and 50 non-FM controls provided 7 days of data. Cognitive tests (processing speed and working memory) and ecological momentary assessments (pain intensity and self-reported cognitive functioning) were conducted ×5/day. Three-level multilevel models examined contemporaneous and within-day 1-lag pain intensity–cognitive functioning associations. Interaction terms assessed possible moderating effects of FM status. Momentary increase in pain was associated with increased self-reported cognitive dysfunction, more strongly so for those with FM (B = 0.27, 95% confidence interval 0.22–0.32; non-FM B = 0.17, 95% confidence interval 0.10–0.23). For the FM group, higher pain was associated with longer processing speed; for the non-FM group, higher pain was associated with shorter processing speed. Pain increase did not precede change in subjective or objective cognitive function in the FM group, but reduction in working memory preceded increase in pain intensity. This finding warrants further research attention and, if replicated, could hold prognostic and/or therapeutic potential.
Impact of variability in baseline pain on the placebo response in randomized, placebo-controlled, crossover trials in peripheral neuropathic pain
Authors: Gillving Mimmi , Demant Dyveke , Holbech Jakob V. , Vase Lene , Bach Flemming W. , Jensen Troels S. , Finnerup Nanna B. , Sindrup Søren H. 
Published: June 2021

Abstract
Large placebo responses often negatively affect randomized controlled trials within the pain area. Understanding different possible factors that influence the placebo response is therefore important. In this retrospective analysis, we hypothesized that a large variability in baseline pain score would predict a greater placebo response and analyzed the impact of the coefficient of variation, SD, and difference between the highest and lowest numeric rating scale (NRS) score at baseline on the placebo response. A total of 160 observations on placebo response from 3 controlled clinical trials with a crossover design were included in this study. In general, the placebo response was low with a mean reduction in pain intensity of 0.5 points (range −5 to 7) measured on a 0 to 10 point NRS, and only 15% were placebo responders as defined by more than 30% reduction in NRS pain score from baseline to the end of the placebo treatment period. We found no significant impact of baseline pain coefficient of variation, SD, or the difference between lowest and highest baseline pain score on the placebo response. Placebo response in one trial did not predict placebo response in another trial. A large placebo response was not associated with a large treatment response. In conclusion, in this retrospective data analysis, there was no impact of baseline pain variability on the placebo response in controlled clinical trials with a crossover design in patients with peripheral neuropathic pain.
Using wearable technology to detect prescription opioid self-administration
Authors: Salgado García Francisco I. , Indic Premananda , Stapp Joshua , Chintha Keerthi K. , He Zhaomin , Brooks Jeffrey H. , Carreiro Stephanie , Derefinko Karen J. 
Published: June 2021

Abstract
Appropriate monitoring of opioid use in patients with pain conditions is paramount, yet it remains a very challenging task. The current work examined the use of a wearable sensor to detect self-administration of opioids after dental surgery using machine learning. Participants were recruited from an oral and maxillofacial surgery clinic. Participants were 46 adult patients (26 female) receiving opioids after dental surgery. Participants wore Empatica E4 sensors during the period they self-administered opioids. The E4 collected physiological parameters including accelerometer x-, y-, and z-axes, heart rate, and electrodermal activity. Four machine learning models provided validation accuracies greater than 80%, but the bagged-tree model provided the highest combination of validation accuracy (83.7%) and area under the receiver operating characteristic curve (0.92). The trained model had a validation sensitivity of 82%, a specificity of 85%, a positive predictive value of 85%, and a negative predictive value of 83%. A subsequent test of the trained model on withheld data had a sensitivity of 81%, a specificity of 88%, a positive predictive value of 87%, and a negative predictive value of 82%. Results from training and testing model of machine learning indicated that opioid self-administration could be identified with reasonable accuracy, leading to considerable possibilities of the use of wearable technology to advance prevention and treatment.
Microglial ablation does not affect opioid-induced hyperalgesia in rodents
Authors: Liu Xin , Liu Bo-Long , Yang Qing , Zhou Xiangfu , Tang Shao-Jun 
Published: June 2021

Abstract
Opioids are the frontline analgesics in pain management. However, chronic use of opioid analgesics causes paradoxical pain that contributes to the decrease of their efficacy in pain control and the escalation of dose in long-term management of pain. The underling pathogenic mechanism is not well understood. Microglia have been commonly believed to play a critical role in the expression of opioid-induced hyperalgesia in animal models. We performed microglial ablation experiments using either genetic (CD11b-diphtheria toxin receptor transgenic mouse) or pharmacological (colony-stimulating factor-1 receptor inhibitor PLX5622) approaches. Surprisingly, ablating microglia using these specific and effective approaches did not cause detectable impairment in the expression of hyperalgesia induced by morphine. We confirmed this conclusion with a behavioral test of mechanical and thermal hyperalgesia, in male and female mice, and with different species (mouse and rat). These findings raise caution about the widely assumed contribution of microglia to the development of opioid-induced hyperalgesia.
Reliability and clinical utility of the chronic pain classification in the 11th Revision of the International Classification of Diseases from a global perspective: results from India, Cuba, and New Zealand
Authors: Korwisi Beatrice , Garrido Suárez Bárbara Beatriz , Goswami Subrata , Gunapati Nischala Reddy , Hay Ginea , Hernández Arteaga Manuel Angel , Hill Charlotte , Jones David , Joshi Muralidhar , Kleinstäuber Maria , López Mantecón Ana Marta , Nandi Gargi , Papagari Chandra Shekhar Reddy , Rabí Martínez María del Carmen , Sarkar Biplab , Swain Nicola , Templer Paul , Tulp Maartje , White Naomi , Treede Rolf-Detlef , Rief Winfried , Barke Antonia 
Published: June 2021

Abstract
Chronic pain affects 1 in 5 persons and contributes substantially to the global burden of disease. The 11th Revision of the International Classification of Diseases (ICD-11) includes a comprehensive classification of chronic pain. The aim of this ecological implementation field study was to evaluate the classification's interrater reliability and clinical utility in countries with different income levels. The study was conducted in 4 pain clinics in Cuba, India, and New Zealand. Twenty-one clinicians used the ICD-11 to diagnose and code n = 353 patients with chronic pain. Of these, 111 were assessed by 2 clinicians, and Fleiss' kappa was calculated to establish interrater reliability for any diagnosis assigned to ≥15 patients. The clinicians rated the clinical utility of all diagnoses. The interrater reliability could be calculated for 11 diagnoses. It was substantial for 10 diagnoses and moderate for 1 (kappa: 0.596-0.783). The mean clinical utility of the ICD-11 chronic pain diagnoses was rated as 8.45 ± 1.69/10. Clinical utility was rated higher for ICD-11 than for the commonly used classification systems (P < 0.001, η2 = 0.25) and differed between all centers (P < 0.001, η2 = 0.60). The utility of the ICD-11 diagnoses was rated higher than the commonly used diagnoses in Dunedin and Havana, and no difference was found in Kolkata and Hyderabad. The study showed the high interrater reliability of the new chronic pain diagnoses. The perceived clinical utility of the diagnoses indicates their superiority or equality compared with the classification systems currently used in pain clinics. These results suggest the global applicability of the classification in specialized pain treatment settings.