Analgesic consumption in a large sample of people in musculoskeletal rehabilitation: A descriptive study.

BACKGROUND: Consumption of opioids is increasing worldwide in people with chronic non-cancer pain, although their effectiveness is debated. OBJECTIVES: The aim of the current study was to evaluate analgesic consumption and its association with different variables (demographic variables, pain, anxiety/depression, catastrophism, and kinesiophobia), in the field of musculoskeletal rehabilitation, where no data are available. METHODS: This was a retrospective study over a period of 8 years on people hospitalised for rehabilitation after injury. Participants were classified into 3 categories: no analgesics (NA), non-opioid analgesics (NOA), and opioid analgesics (OPA). ANOVA or chi-squared tests were used to compare the 3 groups. RESULTS: A total of 4,350 people (84% men; mean [SD] age, 44 [11] years) were included. In total, 20% were taking OPA, 40% NOA and 40% NA. In the OPA group, tramadol was mainly used, and the morphine equivalent median dose was 8.3 mg/day. In the NOA group, paracetamol and ibuprofen were mostly used. Symptoms increased progressively across the 3 groups (NA/NOA/OPA), with increased levels of pain severity/interference, anxiety/depression and catastrophizing, and a higher prevalence of neuropathic pain in the OPA group versus the others. CONCLUSIONS: These results are consistent with those found in groups of people with chronic pain taking larger doses of opioids and following opioid reduction or cessation programs. Opioid prescription did not increase over the 8 years, which was reassuring. These factors are important to emphasise because they can be modified in the rehabilitation setting with interdisciplinary management. REGISTRATION: Our database was registered on Mendeley Data.

Should we separately measure the pain parameter of the Constant-Murley score in patients with chronic shoulder pain?

BACKGROUND: The Constant-Murley Score (CMS) is a relatively unique shoulder assessment tool because it combines patient-reported outcomes (pain and activity), performance measurement and clinician-reported outcomes (strength and mobility). With these characteristics, the effect of patient-related psychological factors on the CMS remains debated. We aimed to investigate which parameters of the CMS are influenced by psychological factors by assessing the CMS before and after rehabilitation for chronic shoulder pain. METHODS: This retrospective study screened all patients (18-65 years old) who were admitted for interdisciplinary rehabilitation for chronic shoulder pain (≥ 3 months) between May 2012 and December 2017. Patients with unilateral shoulder injuries were eligible. Exclusion criteria were shoulder instability, concomitant neurological injuries, complex regional pain syndrome (including Steinbrocker syndrome), heavy psychiatric issues, and missing data. The Hospital Anxiety and Depression Scale, Pain Catastrophizing scale, and Tampa Scale of Kinesiophobia were administered before and after treatment. Regression models were used to estimate associations between psychological factors and the CMS. RESULTS: We included 433 patients (88% male, mean age 47±11 years) with a median duration of symptoms of 392.2 days (interquartile range: 266.5-583.5). Rotator cuff issue was present in 71% of patients. During interdisciplinary rehabilitation, patients were followed for a mean of 33.6±7.5 days. The mean CMS at entry was 42.8 ±15.5. The mean gain in CMS after treatment was 10.6 ±10.9. Before treatment, psychological factors were significantly associated with only the pain CMS parameter: -0.37 (95% CI: -0.46 to -0.28), p <0.001. After treatment, psychological factors were associated with the evolution of the four CMS parameters: -0.12 (-0.23 to -0.01) to -0.26 (95% CI: -0.36 to -0.16), p<0.05. CONCLUSIONS: This study raises the question of a distinct assessment of pain when assessing shoulder function with CMS in patients with chronic shoulder pain. The separation of the "pain parameter" from the overall CMS score seems illusory with this tool that is used worldwide. However, clinicians should be aware that psychological factors can negatively influence the evolution of all CMS parameters during follow-up, which argues for a biopsychosocial approach to patients with chronic shoulder pain.

Simple clinical tools improve ability-to-work predictions for individuals 3-24 months after upper limb injury.

BACKGROUND: Despite numerous previous studies, predicting the ability to work (ATW) after an upper limb injury (ULI) remains difficult for those still not working 3-24 months after their initial injury. OBJECTIVES: We aimed to identify simple prognostic characteristics that were associated with the long-term ATW for individuals who remained unable to work several months after the accident that caused their ULI. METHODS: A single-center prospective observational study in a rehabilitation center in the French-speaking part of Switzerland. We included participants who were 18-60 years old, still unable to work because of persistent pain/disability 3-24 months after an ULI, and who were referred to our rehabilitation center for a 1-month intensive interdisciplinary treatment. Data were collected on personal characteristics, body function/structure variables, activity limitations/participation restrictions, and environmental factors. Participants' evolution during rehabilitation was assessed using functional tests/questionnaires and the 7-level self-reported Patient's Global Impression of Change (PGIC) assessment at discharge. Participant outcomes after 1 year were categorized as either able (ATW>0%) or unable (ATW=0%) to work. The best prognostic characteristics were selected by logistic regression analysis. RESULTS: Among the 317 participants, 202 (64%) had an ATW>0% at 1 year. A grip strength ≥16 kg (Jamar Hand Dynamometer score - affected side) and "(I) do not take pain medicine" were independent predictors. Overall, 96% (26/27) of participants with these 2 characteristics had an ATW>0% at 1 year. The simultaneous absence of these characteristics predicted an unfavorable prognosis in 50% (59/119) of participants. For those who also had a positive PGIC score then 100% (25/25) of participants with these 3 characteristics had an ATW>0%; for those without, only 42% (19/45) had an ATW>0%. CONCLUSIONS: Grip strength (≥16 kg) and not taking pain medicine are favorable prognostic factors for an ATW after an ULI. Their absence is associated with a poor ATW prognosis for half of people with ULI and should alert caregivers to risk of long-term absenteeism ("red flags"). Including data from a PGIC further improves the ATW prediction. We recommend that these 3 criteria be systematically evaluated.

Effect of a four-week isocaloric ketogenic diet on physical performance at very high-altitude: a pilot study.

BACKGROUND: A ketogenic diet (KD) reduces daily carbohydrates (CHOs) ingestion by replacing most calories with fat. KD is of increasing interest among athletes because it may increase their maximal oxygen uptake (VO2max), the principal performance limitation at high-altitudes (1500-3500 m). We examined the tolerance of a 4-week isocaloric KD (ICKD) under simulated hypoxia and the possibility of evaluating ICKD performance benefits with a maximal graded exercise bike test under hypoxia and collected data on the effect of the diet on performance markers and arterial blood gases. METHODS: In a randomised single-blind cross-over model, 6 recreational mountaineers (age 24-44 years) completed a 4-week ICKD followed or preceded by a 4-week usual mixed Western-style diet (UD). Performance parameters (VO2max, lactate threshold [LT], peak power [Ppeak]) and arterial blood gases (PaO2, PaCO2, pH, HCO3-) were measured at baseline under two conditions (normoxia and hypoxia) as well as after a 4-week UD and 4-week ICKD under the hypoxic condition. RESULTS: We analysed data for all 6 participants (BMI 19.9-24.6 kg m-2). Mean VO2max in the normoxic condition was 44.6 ml kg-1 min-1. Hypoxia led to decreased performance in all participants. With the ICKD diet, median values for PaO2 decreased by - 14.5% and VO2max by + 7.3% and Ppeak by + 4.7%. CONCLUSION: All participants except one could complete the ICKD. VO2max improved with the ICKD under the hypoxia condition. Therefore, an ICKD is an interesting alternative to CHOs dependency for endurance performance at high-altitudes, including high-altitude training and high-altitude races. Nevertheless, decreased PaO2 with ICKD remains a significant limitation in very-high to extreme altitudes (> 3500 m). Trial registration Clinical trial registration Nr. NCT05603689 (Clinicaltrials.gov). Ethics approval CER-VD, trial Nr. 2020-00427, registered 18.08.2020-prospectively registered.

Healthcare Costs, Time to Fitness for Work, and Related Factors in Chronic Complex Regional Pain Syndrome: A Comparative and Longitudinal Study of 5-Year Follow-Up.

Purpose: To assess and compare the healthcare costs, time to fitness for work (TFW) between chronic complex regional pain syndrome (CRPS) and non-CRPS; and identify factors associated with these outcomes in a comparative longitudinal study. Patients and Methods: 148 patients with chronic CRPS of the hand and 273 patients with chronic hand impairments but without CRPS (non-CRPS) were admitted at a Swiss rehabilitation clinic between 2007 and 2016. Healthcare costs and TFW were retrieved from insurance data over 5 years after the accident. Socio-demographic factors, biopsychosocial complexity measured by means of the INTERMED questionnaire, pain intensity and DASH disability scores were collected during rehabilitation. Generalized estimation equations and Cox proportional-hazards models were used to identify factors associated with outcomes. Results: Healthcare costs were increased by 20% for the CRPS versus non-CRPS group (coefficient = 1.20, 95% CI = 1.08-1.35, p<0.001). The median TFW was longer for CRPS than non-CRPS patients (816 vs 672 days, p = 0.02). After adjusting for covariates, TFW did not differ between the two groups (hazard ratio = 0.94, 95% CI = 0.73-1.21, p=0.61). For CRPS patients, higher healthcare costs were associated with severe or moderate initial injury, high INTERMED or DASH disability scores. Longer TFW were associated with severe initial injury, low educational level, no work contract, and high INTERMED or DASH disability scores. Conclusion: Overall, the healthcare costs were higher for CRPS than non-CRPS patients, but the TFW was comparable. We demonstrated also the significant associations of disability and biopsychosocial factors with the healthcare costs and TFW in CRPS patients.

Prosthetic fitting associated with better survival at 5 years after above-knee amputation due to vascular insufficiency.

BACKGROUND: Individuals requiring non-traumatic Gritti-Stokes amputation or mid-thigh amputation usually have multiple comorbidities that place them at high risk of mortality. OBJECTIVE: To determine survival rate 5 years after Gritti-Stokes and mid-thigh amputation in individuals with vascular insufficiency and to identify the predictors of survival. METHODS: We conducted a retrospective observational study including all individuals with vascular insufficiency who underwent amputation from September 2007 to December 2015 in our University Hospital. The indication for amputation was limb necrosis in 86% of cases, infection in 10%, and complications with the stump (discomfort, neuroma or scar dehiscence) in 4%. Medical records were analysed to determine factors and comorbidities. The date of death was retrieved from the national death registry at a minimum of 5 years after amputation. Cox proportional-hazard regression was used to estimate associations between factors and post-amputation survival with hazard ratios (HR) and 95% confidence intervals (CIs). RESULTS: We included 126 people with vascular insufficiency (83 men), mean age was 70 years [20; 97]; eighty-nine participants (71%) died during the study period. Survival rate was 68% at 1 year, 48% at 3 years and 37% at 5 years. Survival was associated with prosthetic fitting (HR 0.306 [95% CI 0.180; 0.521], p<0.001) and length of stay (HR 0.992 [95% CI 0.987; 0.997], p = 0.003). Conversely, limb necrosis was associated with a lower survival rate (HR 3.801 [95% CI 1.615; 8.949], p = 0.002). In a secondary multivariable analysis, Gritti-Stokes amputation was the only factor positively associated with prosthetic fitting (odds ratio 7.407 [95% CI 2.439; 22.489], p<0.001). CONCLUSIONS: The survival rate at 5 years after Gritti-Stokes and mid-thigh amputation in people with vascular insufficiency was 37%. Prosthetic fitting was independently associated with better survival, and Gritti-Stokes amputation was the only factor positively related to prosthetic fitting.

Development and Validation of Short Forms of the Pain Catastrophizing Scale (F-PCS-5) and Tampa Scale for Kinesiophobia (F-TSK-6) in Musculoskeletal Chronic Pain Patients.

Purpose: Chronic pain is a complex phenomenon. Understanding its multiple dimensions requires the use of a combination of several patient-reported outcome measures (PROMs). However, completing multiple PROMs is time-consuming and can be a burden for patients. The objective of our study was to simultaneously reduce the French versions of the Pain Catastrophizing Scale (PCS) and Tampa Scale for Kinesiophobia (TSK) questionnaires to enable their use in an ambulatory and clinical settings. Patients and Methods: We conducted a clinical study between May 2014 and August 2020 in our rehabilitation center. 1428 chronic musculoskeletal pain patients (CMSP) were included. The originality of our approach is that the reduction method included qualitative as well as quantitative analyses. The study was divided into two parts: 1) reduction of the questionnaires (n=1363) based on internal consistency (item-to-total correlation), principal component analysis (item loadings), Rasch analysis (infit/outfit), floor and ceiling effect (quantitative analyses) and expert judgment of items (qualitative analysis), and 2) validation of the reduced questionnaires (n=65), including test-retest reliability (intraclass correlation coefficient [ICC]), homogeneity (Cronbach α), criterion validity (Pearson correlation [r] with the long-version score), determination of the pathological cutoff and Minimal Clinically Important Difference (MCID). The two full-length questionnaires include 30 items in total. Results: The reduction resulted in a 5-item PCS (score 0-20) and 6-item TSK (score 0-24). Psychometric properties of the reduced questionnaires were all acceptable as compared with other version (α=0.89 and 0.71, ICC=0.75 and 0.60, r=0.86 and 0.70, MCID=2 and 2 for PCS and TSK, respectively) while keeping the structure and coherence of the long versions. Conclusion: The two reduced versions of the PCS and TSK can be used in CMSP patient. As their administration only requires a few minutes, they can be implemented in outpatient consultation as well as in clinical settings.

Genome-Wide Epigenomic Analyses in Patients With Nociceptive and Neuropathic Chronic Pain Subtypes Reveals Alterations in Methylation of Genes Involved in the Neuro-Musculoskeletal System.

Nociceptive pain involves the activation of nociceptors without damage to the nervous system, whereas neuropathic pain is related to an alteration in the central or peripheral nervous system. Chronic pain itself and the transition from acute to chronic pain may be epigenetically controlled. In this cross-sectional study, a genome-wide DNA methylation analysis was performed using the blood DNA reduced representation bisulfite sequencing (RRBS) technique. Three prospective cohorts including 20 healthy controls (CTL), 18 patients with chronic nociceptive pain (NOCI), and 19 patients with chronic neuropathic pain (NEURO) were compared at both the single CpG and differentially methylated region (DMR) levels. Genes with DMRs were seen in the NOCI and NEURO groups belonged to the neuro-musculoskeletal system and differed between NOCI and NEURO patients. Our results demonstrate that the epigenetic disturbances accompanying nociceptive pain are very different from those accompanying neuropathic pain. In the former, among others, the epigenetic disturbance observed would affect the function of the opioid analgesic system, whereas in the latter it would affect that of the GABAergic reward system. This study presents biological findings that help to characterize NOCI- and NEURO-affected pathways and opens the possibility of developing epigenetic diagnostic assays. PERSPECTIVE: Our results help to explain the various biological pathways modifications underlying the different clinical manifestations of nociceptive and neuropathic pains. Furthermore, the new targets identified in our study might help to discover more specific treatments for nociceptive or neuropathic pains.

Development and validation of a short version of the French Hand Function Sort questionnaire in vocational rehabilitation.

BACKGROUND: The Hand Function Sort (HFS) is a pictorial self-administered questionnaire with 62 items. It is a valid and reliable scale focused on the physical function of the upper limbs. It is used to predict the return to work. OBJECTIVES: We aimed to develop and validate a short version of the French version of the HFS (HFS-F) to simplify its use in clinical practice. METHODS: We included patients with upper-limb chronic pain hospitalised for vocational rehabilitation from 2012 to 2019. Vocational rehabilitation aims to improve the autonomy of patients to regain their previous working capacity. The 62 items of the HFS-F were analysed in terms of patient and expert assessments, floor/ceiling effect, item-to-total correlation, principal component analysis, and Rasch analysis. A short HFS-F was developed. Thereafter, we assessed its internal consistency, test-retest reliability, criterion validity with the full-length HFS-F, construct validity with different scales (Disabilities of the Arm, Shoulder, and Hand [DASH]; Brief Pain Inventory [BPI]; Hospital Anxiety and Depression [HAD]), standard error of measurement (SEM), and minimal detectable change (MDC). RESULTS: Six experts were consulted, 34 patients were interviewed, and 629 questionnaires were analysed. Among the items, 25 were selected after the final round with the six experts. The internal consistency and test-retest reliability were excellent (Cronbach α=0.95, intraclass correlation coefficient=0.92, 95% confidence interval [95% CI] 0.87 to 0.95). The correlation coefficient between scores of the short and full-length HFS-F was 0.841 (95% CI: 0.752 to 0.897, P<10-4), and those between the short HFS-F score and the DASH, BPI, HAD-Anxiety, and HAD-Depression scores were -0.816 (95% CI: -0.714 to -0.881, P<10-4), -0.529 (95% CI: -0.338 to -0.674, P<10-4), -0.451 (95% CI: -0.244 to 0.614, P=0.0001), and -0.360 (95% CI: -0.140 to -0.542, P=0.0018), respectively. The SEM and MDC values were estimated at 6/100 and 17/100, respectively. CONCLUSIONS: A short version of the HFS-F was developed and validated. We named this questionnaire the 25 HFS-F.

Determination of Perceived Levels of Physical Work Demand Thresholds, and Reliability and Responsiveness of the Modified-Spinal Function Sort Questionnaire in a Multidisciplinary Occupational Rehabilitation Setting.

PURPOSE: To determine the levels of perceived work demand capacity corresponding to the Modified Spinal Function Sort (M-SFS) score and precise reliability validity and responsiveness. METHODS: This prospective validation study included patients with chronic musculoskeletal impairments who underwent multidisciplinary occupational rehabilitation. After determining the percentiles of the work demand thresholds corresponding to the spinal function sort (SFS), the percentiles were transposed to the M-SFS. Reliability was assessed using the intraclass correlation coefficient and limits of agreement. Correlations with other questionnaires and a lifting task were measured to assess validity. Responsiveness was determined using anchor- and distribution-based approaches. RESULTS: 288 patients were included. The following thresholds were obtained for the M-SFS: 0-43 points, minimal; 44-50, very light; 51-58, light; 59-64, light to medium; 65-70, medium; 71-76, heavy; and 77-80, very heavy. Reliability was confirmed. The correlation between the M-SFS and SFS scores was good at 0.89 (95% CI, 0.86-0.91) and moderate according to the PILE-test result of 0.60 (95% CI, 0.50-0.67). We could not calculate a valid anchor-based minimal clinically important difference. The standard error of measurement was 3.9 points, and the smallest detectable change was 10.8 points. CONCLUSIONS: On the basis of the comparison of the M-SFS and SFS scores, the M-SFS score can be interpreted in relation to the levels of work demand. This study confirms the good reliability and validity of the M-SFS questionnaire in assessing perceived physical capacity. Further studies are needed to determine its responsiveness.

The self-assessment INTERMED predicts healthcare and social costs of orthopaedic trauma patients with persistent impairments.

OBJECTIVE: To use the self-assessment INTERMED questionnaire to determine the relationship between biopsychosocial complexity and healthcare and social costs of patients after orthopaedic trauma. DESIGN: Secondary prospective analysis based on the validation study cohort of the self-assessment INTERMED questionnaire. SETTING: Inpatients orthopaedic rehabilitation with vocational aspects. SUBJECTS: In total, 136 patients with chronic pain and impairments were included in this study: mean (SD) age, 42.6 (10.7) years; 116 men, with moderate pain intensity (51/100); suffering from upper (n = 55), lower-limb (n = 51) or spine (n = 30) pain after orthopaedic trauma; with minor or moderate injury severity (severe injury for 25). MAIN MEASURES: Biopsychosocial complexity, assessed with the self-assessment INTERMED questionnaire, and other confounding variables collected prospectively during rehabilitation. Outcome measures (healthcare costs, loss of wage costs and time for fitness-to-work) were collected through insurance files after case settlements. Linear multiple regression models adjusted for age, gender, pain, trauma severity, education and employment contract were performed to measure the influence of biopsychosocial complexity on the three outcome variables. RESULTS: High-cost patients were older (+3.6 years) and more anxious (9.0 vs 7.3 points at HADS-A), came later to rehabilitation (+105 days), and showed higher biopsychosocial complexity (+3.2 points). After adjustment, biopsychosocial complexity was significantly associated with healthcare (ß = 0.02; P = 0.003; expß = 1.02) and social costs (ß = 0.03; P = 0.006, expß = 1.03) and duration before fitness-to-work (ß = 0.04; P < 0.001, expß = 1.04). CONCLUSION: Biopsychosocial complexity assessed with the self-assessment INTERMED questionnaire is associated with higher healthcare and social costs.

Psychiatric Comorbidity and Complex Regional Pain Syndrome Through the Lens of the Biopsychosocial Model: A Comparative Study.

PURPOSE: To compare the prevalence of psychiatric comorbidity between patients with complex regional pain syndrome (CRPS) of the hand and non-CRPS patients and to assess the association between biopsychosocial (BPS) complexity profiles and psychiatric comorbidity in a comparative study. PATIENTS AND METHODS: We included a total of 103 patients with CRPS of the hand and 290 patients with chronic hand impairments but without CRPS. Psychiatric comorbidities were diagnosed by a psychiatrist, and BPS complexity was measured by means of the INTERMED. The odds ratios (OR) of having psychiatric comorbidities according to BPS complexity were calculated with multiple logistic regression (adjusted for age, sex, and pain). RESULTS: Prevalence of psychiatric comorbidity was 29% in CRPS patients, which was not significantly higher than in non-CRPS patients (21%, relative risk=1.38, 95% CI: 0.95 to 2.01 p=0.10). The median total scores of the INTERMED were the same in both groups (23 points). INTERMED total scores (0-60 points) were related to an increased risk of having psychiatric comorbidity in CRPS patients (OR=1.46; 95% CI: 1.23-1.73) and in non-CRPS patients (OR=1.21; 95% CI: 1.13-1.30). The four INTERMED subscales (biological, psychological, social, and health care) were correlated with a higher risk of having psychiatric comorbidity in both groups. The differences in the OR of having psychiatric comorbidity in relation to INTERMED total and subscale scores were not statistically different between the two groups. CONCLUSION: The total scores, as well as all four dimensions of BPS complexity measured by the INTERMED, were associated with psychiatric comorbidity, with comparable magnitudes of association between the CRPS and non-CRPS groups. The INTERMED was useful in screening for psychological vulnerability in the two groups.

Task-Contingent Persistence is Related to Better Performance-Based Measures in Patients with Chronic Musculoskeletal Pain.

Purpose: Pacing, avoidance, and overdoing are considered the three main behavioral strategies, also labeled activity patterns. Their relationship with functioning of patients with chronic pain is debated. The purpose of this study was to measure the influence of activity patterns on lifting tasks commonly used in daily life. Method: We performed a monocentric observational study and included patients performing Functional Capacity Evaluation (FCE). Avoidance, pacing, and persistence were assessed with using the Patterns of Activity Measures-Pain (POAM-P). Maximal safe performance was measured for floor-to-waist, waist-to-overhead, horizontal lift, and carrying with dominant-hand tests according to the FCE guidelines. Descriptive statistics, associations of POAM-P subscales with various sociodemographic variables, and correlations are presented. Standard multiple linear regression models were applied to measure the associations between FCE tests and POAM-P subscales, adjusting for the following potential confounders: age, gender, body mass index (BMI), pain severity, trauma severity, localization of injury, and education. Results: Persistence was significantly positively associated with performance on the 4 FCE tests: floor-to-waist (coefficient = 0.20; p=0.001), waist-to-overhead (coefficient = 0.13; p=0.004), horizontal lift (coefficient = 0.31; p ≤ 0.001), and dominant-handed lifting (coefficient = 0.19; p=0.001). Pacing was found to have a negative influence on the carrying dominant-hand test (coefficient = -0.14; p=0.034), and avoidance was not found to have an influence on the 4 FCE tests. Conclusion: This study shows that task-persistence pattern is positively associated with physical performance in FCE, whereas pacing can have a negative influence on some tests.

Altered BDNF Methylation in Patients with Chronic Musculoskeletal Pain and High Biopsychosocial Complexity.

PURPOSE: The INTERMED instrument, which was developed to measure patient's biopsychosocial (BPS) complexity, represents a powerful diagnostic and therapeutic tool. Epigenetic changes are the interface between signals from the environment and genetic modifications, affecting gene expression, in particular, by DNA methylation of CpG dinucleotides in promotor regions of the corresponding genes. The brain-derived neurotrophic factor (BDNF) gene plays a crucial role in the central sensitization (CS) of pain. In this study, we hypothesized that chronic pain modifies the methylation levels of the BDNF gene in a manner that is interconnected with the BPS status. PATIENTS AND METHODS: Fifty-eight chronic musculoskeletal pain patients (CMSP) were enrolled in the study. DNA was extracted from blood samples, the methylation levels of 13 CpG sites in the BDNF promoter were measured by pyrosequencing, and association studies with various patient parameters and the INTERMED scores were performed. RESULTS: Interestingly, a negative correlation (-0.40) was found between the total INTERMED scores and the average CpG methylation values of the BDNF gene, but no correlation was observed with the severity of pain, degree of anxiety, depression, or kinesiophobia and catastrophism. Moreover, the association was independent of age, sex and level of comorbidities. CONCLUSION: This result shows that CMSP, in association with its biopsychosocial context, epigenetically decreases the degree of methylation of the BDNF promoter and should therefore increase the level of BDNF transcription. It also suggests a role of the INTERMED tool to detect a relationship between the BPS complexity and the epigenetic control of a target gene. The possible upregulation of BDNF expression might be, at least in part, the signal for chronic pain-induced central sensitization (CS). This could partly explain why patients with a higher level of complexity feel more pain than those with lower complexity.

Cross-cultural adaptation and measurement properties of the French version of the Trinity Amputation and Prosthesis Experience Scales-Revised (TAPES-R).

BACKGROUND: The Trinity Amputation and Prosthesis Experience Scales-Revised (TAPES-R) is a self-administered questionnaire to measure multidimensional adjustment to a prosthetic limb. Our aim was to assess the validity and reliability of the French version of the TAPES-R (TAPES-R-F). MATERIALS AND METHODS: The cross-cultural adaptation was performed according to the recommendations. Factor analysis and Rasch analysis were also performed to allow comparison with the original English version. Construct validity was assessed by measuring the correlations between TAPES-R-F subscores and quality of life, pain, body image satisfaction, anxiety and depression. Internal consistency was measured with Cronbach's α. The standard error of measurement, smallest detectable change, Bland and Altman limits of agreement, and intraclass correlation were the measures of agreement and reliability. RESULTS: No major difficulties were encountered throughout the trans-cultural adaptation process. The final version of the TAPES-R-F was well accepted and understood by the patients. According to the factor analysis, the satisfaction scale should be treated as a one-dimensional construct when used by French-speaking people and should not be separated into two separate subscales, functional and aesthetic, as is the case in the original English version. Our study confirmed that there is a strong relationship between biopsychosocial factors and adjustment to amputation. Cronbach's α > 0.8 for all the subscales. Reliability was good to excellent for all the subscales (ICCs between 0.61 and 0.89). The smallest detectable changes were 0.7, 0.8, 1.3, 0.4, and 1.8 (general adjustment, social adjustment, adjustment to limitation, activity restriction, and global satisfaction with the prosthesis). CONCLUSIONS: The TAPES-R-F is a valid and reliable instrument to assess multidimensional adjustment of French-speaking lower limb amputees. This questionnaire can be used for both clinical assessment and research purposes.

Cross-cultural adaptation and validation of the ABIS questionnaire for French speaking amputees.

Background: The Amputee Body Image Scale (ABIS) and its shortened version (ABIS-R) are self-administered questionnaires to measure body image perception of amputee. Our aim was to assess the validity and reliability of the French ABIS (ABIS-F and ABIS-R-F).Methods: Ninety-nine patients were included. The cross-cultural adaptation was performed according to the recommendations. Construct validity was assessed by measuring the correlation between ABIS-F or ABIS-R-F scores and quality of life, pain, anxiety, and depression. Internal consistency was measured with Cronbach's α. The standard error of measurement, smallest detectable change, Bland and Altman limits of agreement, and intraclass correlation were the measures of agreement and reliability.Results: A highest body image disturbance was associated with lowest quality of life, higher pain, and higher anxiety, and depression. Cronbach's α was 0.91/0.89 (ABIS-F/ABIS-R-F). The standard error of measurement was 5.35/2.28 (ABIS-F/ABIS-R-F). The smallest detectable change was 14.82/6.31 (ABIS-F/ABIS-R-F). The mean difference in ABIS-F score was -3.90 with limits of agreement from -18.71 to 10.92. For ABIS-R-F, the mean difference was -2.12 with limits of agreement from -8.43 to 4.19. Intraclass correlation was 0.87/0.82 (ABIS-F/ABIS-R-F).Conclusions: The French versions ABIS-F and ABIS-R-F share similar psychometric properties, both are as reliable, but ABIS-R-F has a better response structure and is more feasible.Implications for rehabilitationThe quality of life of amputees is impacted by their satisfaction with body imageThe Amputee Body Image Scale questionnaire measures this perception and is available for French-speaking amputeesThe Standard Errors of Measurement proposed could be useful for clinical and research purposesBoth ABIS and ABIS-R showed satisfactory construct validity, internal consistency, and reliabilityThe shortened version has a better response structure and is more readily feasible.

Differences in the miRNA signatures of chronic musculoskeletal pain patients from neuropathic or nociceptive origins.

BACKGROUND: The quality of life for millions of people worldwide is affected by chronic pain. In addition to the effect of chronic pain on well-being, chronic pain has also been associated with poor health conditions and increased mortality. Due to its multifactorial origin, the classification of pain types remains challenging. MicroRNAs (miRNA) are small molecules that regulate gene expression. They are released into the bloodstream in a stable manner under normal and pathological conditions and have been described as potential biomarkers. In the present study, we aimed to investigate whether pain may induce an aberrant, specific dysregulation of miRNA expression, depending on the origin of the pain. METHODS AND FINDINGS: To do so, we measured the expression changes of 184 circulating miRNAs (c-miRNAs) in the plasma samples of patients with different origins of chronic musculoskeletal pain. After statistical analyses, we identified seven c-miRNA candidates that were differentially expressed depending on the nociceptive or neuropathic origin of the pain. We then developed a two c-miRNA signature (hsa-miR-320a and hsa-miR-98-5p) that was able to correctly classify the pain type of 70% of the patients from the validation set. CONCLUSIONS: In conclusion, circulating miRNAs are promising biomarkers to identify and characterize the chronic pain type and to further improve its clinical management.

Low- and High-Altitude Cortisol Awakening Responses Differ Between AMS-Prone and AMS-Resistant Mountaineers.

Background: Mechanisms underlying acute mountain sickness (AMS) remain unclear. Corticosteroids are effective for prevention and treatment suggesting a role for deficient endogenous cortisol. The cortisol awakening response (CAR), the increase in cortisol secretion over the first 30-45 minutes after morning awakening, better reflects the hypothalamic-pituitary-adrenal (HPA) axis than single cortisol measurements. We hypothesized that CAR may be altered in AMS-prone persons. Methods: Upon arrival at 4554 m (high altitude [HA]), 81 mountaineers agreed to participate. The following morning, they gave three saliva samples after awakening (S1: 0 minute, S2: 30 minutes, S3: 45 minutes). AMS was scored with the 1993 Lake Louise Score (LLS, cut-off ≥5). Minimally 4 weeks after descent, saliva was recollected by 58 of 81 participants at low altitude (LA); 382 ± 309 m, mean ± standard deviation). Cortisol was quantified by immunoassay. Three cortisol indices were analyzed: first sample on awakening (S1), CAR (area under curve with respect to S1) and total post awaking cortisol (area under the curve from ground [AUC-G]). Results: AMS prevalence was 30%. At HA compared to LA, S1 (450 ± 190 vs. 288 ± 159 ng/dL, p < 0.001) and AUC-G (387 ± 137 vs. 276 ± 114 ng/dL·min, p < 0.001) were greater, but CAR was not (50 ± 100 vs. 60 ± 81 ng/dL·min, p = 0.550). AMS+ compared to AMS- participants had higher S1 both at HA (495 ± 209 vs. 384 ± 176 ng/dL, p = 0.016) and LA (354 ± 160 vs. 253 ± 142 ng/dL, p = 0.015) and lower CAR at LA (24 ± 87 vs. 79 ± 72 ng/dL·min, p = 0.013). AUC-G was similar in both groups at HA and LA. Conclusions: Some indices of salivary cortisol response upon awakening differ between AMS+ and AMS-, both at HA and LA, suggesting a link between HPA-axis homeostasis and AMS.

Influencing walking behavior can increase the physical activity of patients with chronic pain hospitalized for multidisciplinary rehabilitation: an observational study.

BACKGROUND: Physical therapy and exercising are key components of biopsychosocial rehabilitation for chronic pain. Exercise helps reduce pain and improve physical functions. In addition, a high level of physical activity benefits quality of life and emotional well-being. However, the degree to which hospitalization for extensive rehabilitation effectively increases physical activity has not yet been studied. Therefore, we investigated the physical activity level and the walking behavior of inpatients with musculoskeletal pain. The objectives were 1) to compare physical activity level and walking with or without rehabilitation, 2) to evaluate whether pain site influences physical activity level, and 3) to measure the association between physical activity and pain-related interference with physical functioning. METHODS: During a rehabilitation stay, 272 inpatients with lower limb, spine, or upper limb pain wore an accelerometer over 1 week. We assessed the daily duration of the practice of moderate physical activity and walking. Weekend days, during which the participants went home (days off), were used as a reference for habitual activities. We also evaluated 93 patients before the hospitalization to validate the use of days off as a baseline. Pain interference was measured with the brief pain inventory questionnaire. Generalized linear mixed models analyzed the association between physical activity and walking levels, and 1) rehabilitation participation, 2) pain sites, and 3) pain interference. RESULTS: Weekend days during the stay have similar physical activity level as days measured before the stay (73 min / day at the clinic, versus 70 min / day at home). Rehabilitation days had significantly higher physical activity levels and walking durations than days off (+ 28 min [+ 37%] and + 32 min [+ 74%], respectively). Mixed models revealed 1) a negative association between physical activity and pain interference, and 2) no effect of pain sites. Overall, patients increased their physical activity level independently of reported pain interference. CONCLUSIONS: Despite their painful condition, the inpatients were able to engage themselves in a higher level of physical activity via increased participation in walking activities. We conclude that walking incentives can be a valid solution to help patients with chronic pain be more physically active.