Lenke 5C (lumbar and or thoracolumbar) curve patterns lead to loss of lumbar lordosis which is associated with low back pain in later adulthood. We undertook our study to investigate if brace treatment may have an effect on low back pain and on improving the cosmetic appearance in late adolescents and adults.To estimate if conservative treatment may have an effect on pain in single lumbar curvatures in late adolescent and adult patients with Adolescent Idiopathic Scoliosis (AIS) using a Gensingen Brace by Weiss (GBW).We investigated AIS patients with Lenke 5C pattern who wore a GBW prospectively. The inclusion criteria of our study were age over 15 years, Cobb angle greater than 20° before treatment and Risser 4 or 5. A verbal pain rating scale was used .A total of 26 patients met the inclusion criteria. The average age was 17.7 years and the average Cobb angle was 41.5°. Nineteen patients (73.1%) experienced mild or moderate chronic low back pain before treatment and seven patients (26.9%) were asymptomatic but seeking treatment for cosmetic reasons. At follow-up, a 23% correction of the curve was achieved. All previously symptomatic patients reported that they no longer experienced low back pain after having worn the brace regularly.High correction bracing seems to have a positive effect on the curve and on chronic low back pain in patients with a scoliosis and a Lenke 5C curve pattern.High correction, pattern specific bracing with a GBW may be applied aiming at reducing structural curves and chronic low back pain in late adolescent and adult patients with AIS and with a single lumbar curvature. Scoliosis is a three-dimensional deformity of the spine and the trunk and may lead to functional impairment and pain  other than low back pain and cosmetic concerns  which is produced based on a computer-aided design aiming at a three-dimensional (3D) correction of the spine and trunk and at a restoration of the sagittal profile  measuring the initial trunk rotation using a Scoliometer™, (2) the severity of the Cobb angle, and (3) asking the patients if they had any pain symptoms related to the scoliosis. A verbal pain rating scale (VRS) with a 5-point scale was used  to measure the degree of back pain they had experienced before wearing a brace.After the brace was fitted to the patients, they had an X-ray examination while in the brace, and the exact fit of the brace as well as the correction of the curve as obtained was measured. These in-brace corrections (Cobb angle without brace – Cobb angle in brace = In-brace correction) were documented and the patients were followed up after 6 months while wearing the brace. All the outcome parameters were reassessed at follow-up.The Cobb angle measurements were performed by one of the authors, who is an experienced medical physician with more than 5 years of experience within the field and the X-rays were taken in the radiological department outside our clinic. They were not blinded for the measurements.The patients were also given six sessions of Schroth Best Practice (SBP) exercises by one of the authors  and thus this non-parametric statistical test was used to analyse the data.Data analysis was performed with Statistical Package for the Social Sciences (SPSS) version16 for Windows  Normality analysis was performed with a Shapiro–Wilk test. Descriptive data were reported as frequencies and percentages or means and standard deviations (s.d.) as appropriate. Pre-treatment and post-treatment measurements were compared using the Wilcoxon signed-rank test as the data were not normally distributed  which are generally recognised, and evidence-based. Consent had been obtained from the patients and in the case of minors from their legal guardians for publication of their pictures, provided that their names were not mentioned. No personal data were passed on that could have led to the identification of the included patients. All patients who can be seen in the pictures had given their consent for the publication of their pictures in writing.This article followed all ethical standards for research without direct contact with human or animal subjects.There were a total of 39 patients with Lenke 5C curve patterns treated at the clinic between January 2018 and June 2019. Thirty-nine patients were assessed for eligibility and only 26 met our inclusion criteria and were all included in our study . The meap < 0.001), and when compared to Cobb angles at 6 months follow-up (p < 0.001).Mean Cobb angle value obtained before the treatment was 41.5° ± 13.4°  and meanNineteen patients (73.1%) experienced chronic low back pain of mild to moderate degree before the treatment and seven patients (26.9%) were asymptomatic, seeking treatment for cosmetic reasons. At 6-months follow-up, all previously symptomatic patients reported that they no longer experienced low back pain. Thus, bracing may be considered to have the potential to be effective with respect to Cobb angle reduction and pain control .The aims of treatment in our patients were (1) a reduction of scoliosis curvature and (2) reduction of pain. From the results we can see that there is a mean decrease in Cobb angle severity about 23% and ATR measurement from 12.8° ± 4.8° to 6.4° ± 4.5° at 6 months follow up, and the pain symptoms were reportedly absent.Bracing is considered beneficial during growth when the rate of progression was reduced or when the angle of curvature was improved, and this improved the cosmetic appearance as well has been in use addressing the sagittal plane only  even in late adolescent or adult patients, even though the value is of varying degree. It is also still inconclusive, yet the treatment is still ongoing given the brace treatment will continue for 2 years of wearing time to achieve more stability in the correction. But aside from that, the cosmetic appearance did improve as can be seen in our before and after clinical pictures .This is also confirmed with the improvement in trunk rotation as measured in ATR and the improvement in pain symptoms. Thus, our study can be viewed as a pilot study showing that pain and deformity may be reduced when applying high correction braces. The primary aim for the patients in our study was to reduce the deformity, pain being a secondary issue.Our study was designed as a prospective short-term follow-up without an untreated control group. The sample size was small. Therefore, this investigation may be viewed as a pilot investigation while there are limited reports on patients out of the growth phase treated with a brace (Weiss & Turnbull High correction specific bracing with GBW seems to be effective in maintaining or reducing the curvature in late adolescent and adult AIS patients with single lumbar or thoracolumbar curvatures. Additionally, the GBW application seems to have an influence on chronic pain in patients with a lumbar or thoracolumbar curvature.However, because of the small sample size and the study design, a conclusion cannot be drawn.Nevertheless, the findings from our study seem promising enough to justify undertaking a prospective controlled or randomised controlled study to gain definite evidence for or against brace treatment in mature individuals with scoliosis and with cosmetic concerns and or chronic low back pain.


Pain symptoms in the upper abdomen and back are prevalent in 80% of patients with metastatic pancreatic ductal adenocarcinoma (mPDAC), where the current standard treatment is a systemic therapy consisting of at least doublet-chemotherapy for fit patients. Palliative low-dose radiotherapy is a well-established local treatment option but there is some evidence for a better and longer pain response after a dose-intensified radiotherapy of the primary pancreatic cancer (pPCa). Stereotactic body radiation therapy (SBRT) can deliver high radiation doses in few fractions, therefore reducing chemotherapy-free intervals. However, prospective data on pain control after SBRT of pPCa is very limited. Therefore, we aim to investigate the impact of SBRT on pain control in patients with mPDAC in a prospective trial.This is a prospective, double-arm, randomized controlled, international multicenter study testing the added benefit of MR-guided adaptive SBRT of the pPca embedded between standard of care-chemotherapy (SoC-CT) cycles for pain control and prevention of pain in patients with mPDAC. 92 patients with histologically proven mPDAC and at least stable disease after initial 8 weeks of SoC-CT will be eligible for the trial and 1:1 randomized in 3 centers in Germany and Switzerland to either experimental arm A, receiving MR-guided SBRT of the pPCa with 5 × 6.6 Gy at 80% isodose with continuation of SoC-CT thereafter, or control arm B, continuing SoC-CT without SBRT. Daily MR-guided plan adaptation intents to achieve good target coverage, while simultaneously minimizing dose to organs at risk. Patients will be followed up for minimum 6 and maximum of 18 months. The primary endpoint of the study is the “mean cumulative pain index” rated every 4 weeks until death or end of study using numeric rating scale.An adequate long-term control of pain symptoms in patients with mPDAC is an unmet clinical need. Despite improvements in systemic treatment, local complications due to pPCa remain a clinical challenge. We hypothesize that patients with mPDAC will benefit from a local treatment of the pPCa by MR-guided SBRT in terms of a durable pain control with a simultaneously favorable safe toxicity profile translating into an improvement of quality-of-life.German Registry for Clinical Trials (DRKS): DRKS00025801. Meanwhile the study is also registered at ClinicalTrials.gov with the Identifier: NCT05114213. Pancreatic cancer is the third leading cause of cancer-related death in the United States and Europe, but comes at 9th place in incidence, reflecting the high burden and lethality of this cancer type , 2. The Adequate pain control is often difficult to achieve due to the infiltrative growth of the primary tumor and the limited treatment options. Chemotherapy itself was shown to have an impact on pain with response rates up to 67% . HoweverConventional short-course radiotherapy, a well-established treatment option for cancer-related pain , has beeThe aforementioned paves the way for stereotactic body radiotherapy (SBRT), where escalated radiation doses are delivered in few ambulatory treatment fractions and can therefore be seamlessly integrated into full-dose systemic therapy regimens. SBRT has proven to be an efficacious and cost-effective  treatmenSo far, prospective data on pain control after SBRT is limited. Additionally, evidence about SBRT for primary pancreatic tumor in metastatic patients is very scarce and mainly of retrospective nature. This indicates the need for a well-designed prospective trial with thorough evaluation of pain symptoms and its outcome after SBRT of the primary tumor. Therefore, we aim to investigate the impact of SBRT to the primary tumor in metastasized pancreatic cancer patients on pain control in a prospective randomized trial. SBRT will be performed using a MR-LINAC platform, a hybrid machine combining a linear accelerator (LINAC) with a MRI scanner allowing for on-table MR imaging with gated treatment and daily plan adaptions based on the current anatomy. This technology enables to deliver ablative doses, while maintaining the risk of toxicity to the least possible level.MASPAC trial  is a prospective, double-arm, parallel group, randomized controlled, international multi-center study. The trial aims to investigate the benefit of MR-guided SBRT of the primary pancreatic tumor on pain control and prevention of pain in patients with histologically proven mPDAC after an initial course of 8 weeks of standard-of-care palliative chemotherapy (SoC-CT). Only patients with at least stable disease in the restaging after 8 weeks of SoC-CT will be included into the study. Those with progressive disease will be considered screening failures and therefore not eligible for the study. Patients included into the trial are 1:1 randomized to either Arm A, receiving MR-guided SBRT of the primary tumor with continuation of SoC-CT thereafter without any relevant delay , or Arm B, continuing SoC-CT without SBRT of the primary tumor (control arm). Chemotherapy is given in both arms, A and B, according to the current standard of care and at the decision of the treating medical oncologist, consisting of at least a doublet-chemotherapy, and excluding monotherapy regimens. Patients will be followed up for a minimum of 6 months and a maximum of 18 months. Figure As outlined above, we aim to primarily test the efficacy of additional SBRT on pain control. Therefore, the primary endpoint of the study is the “mean cumulative pain index” (MCPI); calculated as the area under the curve (AUC) of pain scores, rated every 4 weeks until death or end of follow-up using the NRS with values from 0 (= no pain) to 10 (= worst pain). Pain will be assessed as patient reported outcome and indirectly derived from pain medication used by the patient. The AUC results from joining the point s  over the individual follow-up time, divided by the total follow-up time. It is anticipated that intercurrent events  need to be considered for a reliable interpretation of the primary endpoint.Secondary endpoints include average pain on NRS at 24 weeks, time interval until definitive deterioration (= increase of average pain on NRS of 3 points over baseline sustained over 4 weeks), biliary complications, defined as cholangitis or post-hepatic cholestasis requiring drainage or stenting, nutritional status measuring bioimpedance-derived phase angle (BIA) every 12 weeks and death from any cause. Further secondary endpoints are treatment toxicity according to CTCAE v5.0 and quality of life (QoL) assessment using the Euro-QoL 5 dimensions questionnaire (EQ-5D-5L) and FACT-Hepatobiliary Symptom Index—(FHSI-8).A sample size of 92 patients is aimed to be recruited. The enrollment period is planned for 24 months with a minimum follow-up of 6 months and a maximum follow-up of 18 months. Participating centers are three university hospitals in Germany and Switzerland . The inclusion and exclusion criteria are outlined in Table Patients found eligible for study participation and from whom written informed consent was obtained during screening period, will be included. Patients will be registered through a computer system and a study-ID will be assigned by the institute for biometrics and epidemiology (IBE) in Munich via the same computer system with stratification according to age and ECOG.In arm A, the primary tumor is treated with SBRT in 5 fractions on a MR-LINAC platform in breath-hold technique. The MR-LINAC is a CE-mark approved medical device and already in use in clinical routine. It integrates MR imaging and a LINAC into a hybrid system allowing for on-table radiotherapy plan adaptation according to the daily anatomy. Daily adaptive planning is performed aiming to maintain stringent dose constraints for organs at risk (OAR), such as the duodenum, stomach, bowel, liver, kidneys and the spinal cord, while trying to give the full dose of planned 6.6 Gy prescribed at the 80% isodose level to the target volume. SBRT will be performed in a few days straight after randomization into arm A between two cycles of SoC-CT, but not concurrently to chemotherapy.All patients in study arm A and B will rate their pain in the abdominal region on a NRS and report their concomitant medication at baseline and all 4 weeks thereafter. They will undergo at baseline, 4 and 12 weeks after baseline and every 12 weeks thereafter a more intensive assessment with physical examination, laboratory values, body impedance analysis (BIA) in order to monitor nutritional status, examination and reporting of adverse events as well as of QoL via answering questionnaires and answer the Brief pain inventory. Review of imaging will be performed 12 weeks after randomization and then every 12 weeks thereafter. Additionally, blood collection will be performed at randomization and 4 weeks and 24 weeks after that to evaluate predictors of treatment response using deep immune phenotyping, metabolomics and whole blood transcriptomics. Table Any adverse event (AE) occurring between the visit with the first intervention to the subject and the last visit with the last individual specific examination of the subject will be documented and evaluated in the electronic case report form (eCRF). Every unforeseen or unfavorable medical occurrence in a patient including any abnormal sign , symptom, or disease, temporally associated with the patients’ involvement in the clinical study, whether or not considered related to participation in the clinical study is defined as an adverse event. Seriousness, intensity (Grade 0–5) and causality to the study intervention  will be determined. During the clinical study, quality control and quality assurance will be ensured through central monitoring.Whenever a subject is withdrawn from the study, the circumstances of the withdrawal or discontinuation will be recorded in detail in the CRF  and a complete final examination as scheduled for the termination visit should be conducted.If a subject does not return for a scheduled visit, every effort should be made to contact the subject .In any circumstance, every effort should be made to document subject outcome, if possible. In case of a dropout due to an adverse event, the subjects should be monitored outside the trial as long as medically indicated.The study will be conducted in accordance with the provisions of the Declaration of Helsinki, the International Conference on Harmonization “Good Clinical Practices,” and the respective national regulations.Participating centers have to provide written approval of the institutional medical ethics committee. The study was approved by the ethics committee at the leading center in Munich (Project Number 20-0973), in Zurich (BASEC-Nr. 2021-01427) and in Heidelberg.https://www.bauchspeicheldruese-pankreas-selbsthilfe.de/) and “Deutsche Pankreashilfe” (https://www.pankreashilfe.de/), have been introduced to the trial concept and were given the opportunity to contribute to protocol and outcome measures. The content of this trial will be presented to these patient self-help groups and will be made available online as soon as ethics approval has been granted.Two patient support groups, “Arbeitskreis der Pankreatektomierten”  which is formally defined as the cumulative pain index calculated via the trapezoid rule over the complete time of follow-up (AUC) and divided by the number of the observed 4 weeks periods. A simple example is given below. At present, no data is available to perform an informed sample size calculation for our study. We also do not have access to documented longitudinal pain data in a comparable population. For an approximative sample size guess we used pre- and post- data on pain over a period of 6 months reported by Gourgou et al. .0 + W24) · 0.5 · 24.The calculation of the endpoint over the 24 weeks uses AUC = (W0 + W24) · 0.5 · 24/6 = (W0 + W24) · 2.The MCPI over 24 weeks (24 = 6 · 4) is given by MCPI = AUC/6 = (WGroup I0 = 43.9 at baseline (σ0 = 30.7 Std)W24 = 19.3 after 24 weeks FU (σ24=25.0 Std)WMCPI: (43.9+19.3) · 2 = 126.4 Std: 111.4Group II0 = 46.3 at baseline (σ0=30.5 Std)W24 = 26.4 after 24 weeks FU (σ24 = 23.8 Std)WMCPI: (46.3+26.4) · 2 = 145.4 Std: 108.6 Here, we use the conservative assumption of a perfect correlation between both measurements (W0 and W24) and calculate Var(MCPI) = 4 · [ σ02 + σ242 + 2 · σ0 · σ24]. If the MCPI should be reduced from 132 to 66 assuming a standard deviation (Std) of 110, a total of 46 patients per group are needed in order to assess this difference with a power of 80% on a two-sided 5% significance level.The pain measurement data are as follows:This clinical study will be analyzed according to the intention-to-treat  principle. The per protocol (PP) population is a subset of the ITT population and is defined as the group of subjects who had no major protocol violations, received a predefined minimum dose of the treatment and underwent the examinations required for the assessment of the endpoints at relevant, predefined times. The analysis of the PP group will be performed as a sensitivity analysis.The primary analysis will test a primary endpoint with two components: MCPI and OS. The assessment on the MCPI uses a stratified Mann–Whitney-test. The assessment of the second component OS uses a stratified Cox model. A hierarchical testing will be performed to adjust for the multiple testing implied by the two components of the primary endpoint.Furthermore, a sensitivity analysis will adjust for unequal observation time and use the difference in pain cumulated over 1 year between both treatment groups. Here, we follow the hypothetical estimand strategy for dealing with intercurrent events, wanting to know what outcomes would have been observed if patients had survived 1 year . In thisTo avoid bias introduced by ICEs regarding the treatment effect on pain, the concept of joint modelling  will be We have no access to documented longitudinal pain data. Therefore, we use a sample size recalculation on unblinded data performed 1 year after the 80th patient was included into the study. This allows sample size adjustments due to unknown treatment effects and variance and allows the review of the actual study data. It also requires strict firewalls to prevent leakage of information about adaptive rules or decisions .Recruitment is planned to start in October 2021 and the recruitment period extends over 2 years, the last patient included in trial will be followed for 6 months. Accordingly, completion of recruitment is expected by October 2023 and the last patient visit by April 2024. First results of the main analysis should be available by end of 2024. The principal investigators are responsible for the project management and study conduct in collaboration with medical staff at every site. The contract research organization is responsible for the safety management  and the monitoring. The statistical plan and data analysis is provided by the Institute for Medical Information Processing, Biometry, and Epidemiology before database closure.An adequate and long-term control of pain symptoms in patients with mPDAC is an unmet clinical need. Although recent advances in chemotherapy have resulted in a moderate improvement of life expectancy for those patients in good performance state –11, loca3, V20 Gy < 5 cm3, and V10 Gy < 10 cm3. The mean PTV was quite large with a volume of 188 cc and a median volume of 147 cc—which is larger compared to that treated with SBRT for LAPC [There is scarce literature on SBRT in metastatic pancreatic cancer patients and only some retrospective and few prospective data on its effectiveness for pain control of primary pancreatic cancer. One retrospective single-institutional study investigating the role of SBRT in a cohort of metastatic pancreatic cancer patients that evaluated oncological outcome and toxicity of treatment can be found , but no for LAPC . SBRT offor LAPC . Pain reThis finding of good pain control was confirmed by a recently published systematic review investigating pain relief by SBRT in LAPC , with anOverall, there is some evidence to underpin the rationale of a good and durable pain control of primary pancreatic cancer by SBRT in mPDAC. However, in light of the overall limited prognosis and high burden of patients with mPDAC this intervention has to be tested in a prospective randomized trial, which is exactly the purpose of our study.The treatment should not only be effective in terms of pain control but also accompanied by an acceptable toxicity profile. SBRT of the primary tumor in LAPC with 5 fractions of 6.6 Gy was shown to have a reasonable toxicity profile on a conventional LINAC with 11% late ≥ G2 toxicity , which iIn metastatic patients the risk–benefit ratio has to be more beneficial compared to a curative situation, considering the limited prognosis and therefore asking for a focus on QoL. Image-guided radiotherapy is today based on cone-beam CT imaging (CBCT), which does not allow accurate visualization of the pancreas and the OAR in close proximity , leading to difficulties to precisely deliver radiation on a daily basis.Visualization of OAR is more accurate on Magnetic Resonance Imaging, which provides a better soft tissue contrast compared to CT and/or CBCT. Recently developed MR-LINAC hybrid devices allow for MR image-guided radiation therapy (MRgRT) and achieve an improved sparing of OAR , which aBased on this background, we hypothesize that patients with metastatic pancreatic cancer will benefit from local treatment of the primary tumor by MR-guided SBRT in terms of a long pain control with a simultaneously safe toxicity profile translating into an improvement of quality of life. This will be tested in this prospective, double-arm, parallel group, randomized controlled, international multi-center study aiming to include in total 92 patients. Findings of this trial will provide the basis for the decision whether SBRT should be added to SoC-CHT in patients having a stable disease after initial 8 weeks of systemic treatment.


Beverly E. ThornDepartment of Psychology, The University of Alabama, Tuscaloosa, Alabama, USACONTACT Beverly E. Thorn bthorn@ua.edu© 2019 The Author(s). Published with license by Taylor & Francis Group, LLC.http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.This is an Open Access article distributed under the terms of the Creative Commons Attribution License . Treatment, when available, is usually biomedical, expensive, and fraught with undesirable side effects. Psychosocial treatments show promise as adjuncts or alternatives, but are usually unavailable to those with low SES, and have not been adapted for patients with low education or literacy levels. Many researchers and practitioners have questioned the feasibility of an approach such as cognitive-behavioral therapy (CBT) for people facing the challenges of limited resources, including low educational attainment and low literacy. CBT requires a certain amount of abstract thinking and problem solving, utilizes written workbooks, handouts and worksheets, and assigns homework, thus requiring more patient effort than passive treatments like taking analgesic medication or receiving biomedical interventions. This presentation will detail a multi-year effort to adapt (simplify) and test the efficacy of patient materials and procedures targeted for highly disadvantaged individuals with the compound risks associated with low-income, including severe and complex pain problems, low-literacy, and minority group membership (African-American). The process of patient-centered adaptation, recruitment, retention, and data collection will be highlighted, and outcomes will be reported. Implementation, durability, and sustainability considerations will be discussed.Understand the reasons for appropriate adaptations of patient materials for individuals with chronic illness.Learn the basics of adaptation of patients materials based on literacy considerations.Understand the basics of biopsychosocial treatment process adaptations to facilitate retention and participation in pain management programs.Learn the evidence base for adapted (simplified) group pain management programs.Understand the challenges of implementation, durability, and sustainability of pain self-management programs.Learning Objectives:Brigitte L. KiefferCONTACT Brigitte L. Kieffer brigitte.kieffer@douglas.mcgill.ca© 2019 The Author(s). Published with license by Taylor & Francis Group, LLC.http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.This is an Open Access article distributed under the terms of the Creative Commons Attribution License . Published with license by Taylor & Francis Group, LLC.http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.This is an Open Access article distributed under the terms of the Creative Commons Attribution License .Although it has to be assessed differently in specific tissues for various chronic pain conditions, there are some common underlying mechanistic features, such as central integration (wind-up), centralized facilitation (widespread pain and sensitization), and impaired descending pain inhibition.As these mechanisms respond differently to, e.g. gabapentinoids, SNRIs, or opioids, mechanistic diagnostic screening tools are important for individualized profiling of patients and hence selecting the drugs which may have the most beneficial effects in patients with different manifestations of sensitization. In recent years, we have also used individualized pain profiling of osteoarthritis patients prior to, e.g. knee replacement surgery and found that specific profiles can predict which patients are the most vulnerable to develop chronic post-operative pain.Challenges and perspectives to utilize such tools for diagnosis of musculoskeletal sensitization, for management, and ultimately for preventing chronic pain will be highlighted.


Purpose: the evaluation of body image perception, pain coping strategies, and dream content, together with phantom limb and telescoping phenomena in patients with sarcoma who underwent surgery for limb amputation. Material and Methods: consecutive outpatients were evaluated at T0 (within 3 weeks after surgery) and T1 (4–6 months after surgery) as follows: demographic and clinical data collection; the Groningen Questionnaire Problems after Arm Amputation; the West Haven-Yale Multidimensional Pain Inventory; the Body Image Concern Inventory, a clinical trial to identify telescoping; and a weekly diary of dreams. Dream contents were coded according to the Hall and Van de Castle coding system. Results: Twenty patients completed the study . All subjects experienced phantom limb and 35% of them experienced telescoping soon after surgery, and 25% still after 4–6 months. Both at T0 and T1, that half of the subjects reported dreams about still having their missing limbs. At T1 the patients’ perceptions of being able to deal with problems were lower, and pain and its interference in everyday life were higher yet associated with significant engagement in everyday activities and an overall good mood. The dream content analysis highlighted that males were less worried about health problems soon after amputation, and women showed more initial difficulties that seemed to be resolved after 4–6 months after surgery. Conclusions: The dream content analysis may improve clinicians’ ability to support their patients during their therapeutic course. Over the years, many authors have defined body schema, body image, and body awareness in different ways. Body image is referred to the mental representation of the body and its physical features ,2. It isThe self-concept schema depends on “cognitive generalizations about oneself derived from past experiences”. Such experiences lead and guide the processing of self-related information acquired from social knowledge . Self-scDifferences have been found among categories in determining self-schema. Men’s and women’s awareness levels of body parts are diverse. For men, body awareness has more permanence compared to women’s, meaning that they are more aware of their body parts. Additionally, left-handed people seem to be also more certain in perceiving their body senses, compared to right-handed people, while the latter showed less body divergence, meaning they have fewer clearness levels of images of different body parts . Body awInformation about body image is differently interpreted by each individual, also concerning a potentially worrisome physical appearance . Some peThese phenomena can significantly alter the function of the body and can affect the body image and, ultimately, psychosocial well-being  and the In amputees, phantom limb sensations and telescoping are widely present with most individuals experiencing some type of phantom phenomena at some point, post-amputation ,34,35,36The phenomenon of the phantom limb may be considered as an alteration of the sensory-motor pathway. Its origins are not fully understood. The contributions of the central nervous system (CNS) and/or the peripheral nervous system (PNS) are still under debate. Recent findings suggest that both peripheral and central mechanisms, including neuroplastic changes in cortical neural circuits, can contribute to PLS and in particular to phantom limb pain (PLP) . CurrentThe human brain has the power to undergo plastic changes after an alteration in cortical circuits, which are, for a large part, responsible for the conscious awareness of the body, so-called body image. Can unconscious or less conscious processes, that contribute defining body schema, undergo similar adapting changes , and howDream content analysis may be considered an indicator of the internalization of the above-mentioned modifications.A single definition of dream and dreaming is not possible. Dreaming is, at least in part, a mental experience that can be described during waking consciousness .Dreaming should not be exclusively defined as a non-conscious electrophysiological state. Neurobiological theories of dreams state that the meaning of dreams should be considered clearly “transparent” and not elaborated ,42. HobsDomhoff hypothesized a continuity between dreams and waking life in the sense that “the concerns people express in their dreams are the concerns they have in waking life” ,45. AddiFollowing Domhoff’s hypothesis, the analysis of dream reports may be useful in evaluating the changes of mental body image and self-perception in dreams after patients have experienced different kinds of disease-implicating body disfigurements. Calvin S. Hall and Robert L. Van de Castle ,48 develConsidering that both innate factors and life experiences may affect the body representation in dreams, they assumed that “the frequency with which a dream element appears reveals the concerns and interests of the dreamer”, providing the opportunity “to link dream content with the waking thoughts and behavior of the dreamer” .Many studies evaluated the dream content in healthy volunteers to find common features in people’s dream content ,45,49,50Women have been reported to recall their dreams more often than men. Sexual themes arise more often in men’s dreams, as do aggressions, whereas women’s dreams have more depressive contents ,52.Studies on dream content in amputated or surgically treated patients, analyzing the alterations of the physical aspect and their impact on the quality of life, mostly reported that a majority of amputees continue to dream of themselves with an intact body ,54,55,56The aim of this study is the evaluation of body image perception, pain coping strategies, dream content, and their possible modifications over time, together with phantom limb and telescoping phenomena in patients affected by sarcoma who have undergone surgery for limb amputation, within six months after surgery.Sleep medicine experts evaluated all consecutive outpatients referred to the SC Chirurgia Oncologica Ortopedica- Città della Salute e della Scienza over one year. Inclusion criteria were the diagnosis of bone or soft tissue sarcoma, minimum age 14 years old. Exclusion criteria were impaired cognitive ability (MMSE < 24), psychiatric disease, ray amputations , or previous amputations.Subjects were evaluated at T0 (within 3 weeks after surgery) and T1 (4–6 months after surgery). The evaluation included the following: the Groningen Questionnaire Problems after Arm Amputation (GQPAA), to describe frequency and type of phantom sensation, phantom pain, and stump pain, medical treatment received and their effect, and prosthetic use ; a weeklThe Body Image Concern Inventory (BICI), a brief self-report measure of dysmorphic concern  a clinicDream contents were coded according to the Hall and Van de Castle (1966) coding system. Contents are summarized in the following output categories: Male/Female, Familiarity Friends Family Dead & Imaginary Animal Aggression/Friendliness Befriender Aggressor Physical Aggression Indoor Setting Familiar Setting, Self-Negativity, Bodily Misfortunes, Negative Emotions, Dreamer-Involved Success, Torso/Anatomy, Aggression, Friendliness, Sexuality, Misfortune, Good Fortune, Success, Failure, and Striving.www.dreamresearch.net, accessed on: 14 January 2021).Dreams were recorded using a seven-day dream diary and blindly scored (mixing T0 and T1 dream reports) by a sleep medicine board-certified psychologist; difficult or ambiguous issues were resolved during in-group discussions. The alphanumeric codes were uploaded into a DreamSAT spreadsheet, which provided frequencies for the total series of dream reports and percentage calculations ,59. CodeThe Local Ethical Committee approved the protocol, and all patients (or parents whether under the age) signed the informed consent form.2), and contingencies tables. Results are presented in terms of mean ± SD with significance levels at p ≤ 0.05.Statistical analyses were carried out with IBM SPSS 27.0 for Windows, performing a Wilcoxon Test, the Chi-square test . The mean age was 53.9 ± 24.6, education (years) 7.8 ± 3.4, and 10 patients had a diagnosis of soft tissue sarcoma and 10 of bone sarcoma. Eleven underwent lower limb amputation and 9 upper limb amputation, and pre-surgery pain was present in 13 out of 20 subjects. The mean number of weeks after amputation was at T0 2.6 ± 1.0 and at T1 19.5 ± 4.1.Additional clinical data and Wilcoxon test results performed on BICI and WHYMPI are shown in All our subjects experience PLS at some point in their clinical history, and 1/3 of them experienced telescoping soon after surgery, with 1/4 still after 4–6 months. Both at T0 and T1, that half of the subjects reported dreams about still having their missing limbs.Results showed significant differences at some West Haven-Yale Multidimensional Pain Inventory subscales.Four-six months after surgery, significantly higher scores were obtained on two scales measuring important dimensions of how pain affects patient lives (interference and pain severity) and on patients’ reports of the frequency with which they engage in common everyday activities .Additionally, scales about patients perception of being able to deal with and control their problems (life control) and affective distress, and about the support or concern from spouse or significant other (support), obtained lower scores, along with patients’ perceptions of the degree to which significant others react and respond to them when they know they are in pain, and display negative response to their behaviors and complaints (negative response).p = 0.016), has only been found between pre-surgery pain and early post-amputation telescoping.Crossing pre-surgery pain, amputation types and stump pain with telescoping both at T0 and T1, significance .p < 0.05) higher number of dreams was reported by males  both at T0 and T1.Crossing the number of reported dreams at T0 and T1 in both males and females showed that a statistically significant  and sexuality and more good fortune- and family-related content in their dreams compared to normative data. In addition, at T1 they showed no torso-anatomy references.Females at T0 showed more familiar settings in bodily misfortune and dreamer-involved success, and less friends, friendliness, aggression, and failure, compared to norms. Besides, there were no torso-anatomy references.Females, some months after surgery, showed less aggression, self-negativity, negative emotions, torso-anatomy content, success, and dreamer’s success compared to norms.Males showed, substantially, no significant differences between T0 and T1, whereas women at T0 showed more bodily misfortune, aggression, and familiar settings.The present study analyzes the dream content in amputees, using the Hall and Van de Castle coding system, to understand the possible internalization of body modifications due to amputations and some interesting phenomena such as phantom limb and telescoping that may have significant implications on the quality of life. The results of this study mostly confirm previous literature data on phantom limb phenomenology: all our subjects experience PLS at some point in their clinical history, and 1/3 of them experienced telescoping soon after surgery, with 1/4 still after 4–6 months.The pain inventory showed that, at T1, the patients’ perception of being able to deal with problems is lower and pain and its interference on everyday life is higher, meaning that physical sensation and phantom limb pain are still important issues also after 4–6 months from surgery. Nevertheless, the patients’ reports of the frequency with which they engage in four categories of common everyday activities  is higher at 4–6 months after surgery, as they report an overall good mood. That is probably also because significant others display less negative responses to their pain complaints.Besides, the significant association between pre-surgery pain and telescoping at T0 may mean that pre-surgery pain is predictive of telescoping soon after amputation.In literature, we found suggestions that pre-amputation pain might predispose amputees to PLP . Recent In normal conditions, various factors may influence body image: Body mass index (BMI), family, peers, society, media, culture, self-esteem, gender, age, marital status, education level, smoking status, alcohol consumption, physical activity, weight control behavior, and spirituality ,62. For Pathological conditions can have a significant impact on the body’s internal representation, as well. Indeed, body representation and self-perception rely on cognitive schema and emotional experiences that are strongly linked with what happens in everyday life.For this reason, self-awareness can change during life due to life experiences and pathological conditions that can occur.Although there has been much progress in the surgical treatment of bone and soft tissue sarcomas, amputation is unfortunately still needed in 5–10% of cases  of bone As we previously said, phantom limb sensations are very common in amputees ,33,34,35Phantom limb sensations may include pain, itching, movements, abnormal shape or position, warmth, and cold or electric sensations. Some kind of phantom sensations are present in virtually all patients with limb amputation and may be explained by three theories: the peripheral one theorizes that the impulses carried to the central nervous system, coming from the nerve endings in the stump, are perceived as pertaining to the amputated limb ,64; the If PLS involve the majority of amputees and are still an important issue several months after amputation, as we found in our study, a different and deeper way to analyze the impact of these phenomena on patients life may be useful.If, during waking life, an amputee still feels the presence of the amputated limb, what happens while dreaming? Can the dream be considered a reliable and precocious indicator of what happens in the dreamer’s emotional life?Over the years, some studies have analyzed the dream content using a standardized coding method ,69,70,71In literature, most studies reported that a majority of amputees continue to dream about themselves with an intact body ,46,47,48Bekrater-Bodmann and colleagues in 2015, demonstrated that, although only a minority of dreams in their sample contained bodily impairments, there is a positive relationship between post-amputation pain during wake and the recall of an impaired body representation in dreams . Our preThe dream analysis, in the present study, showed both at T0 and T1 that half of the subjects reported dreams about still having their missing limbs. As we previously said, this evidence underlines the importance of considering the timing of the assessment after amputation. Males both at T0 and T1 reported a statistically significantly higher number of dreams. That is maybe because, as we previously said, men’s body awareness has more permanence compared to women’s .We also found that males, at both T0 and T1, had fewer negative features (such as aggression and negative emotions) and more good fortune and an abundance of family members in their dreams compared to normative data indicating fewer concerns about the surgery, the clinical outcome, and the physical appearance. In addition, at T1 they showed no torso-anatomy references, an indicator of possible disturbance of bodily image  or a real absence of body-image issues.Females at T0 showed more familiar settings, bodily misfortune, and dreamer-involved success, and fewer friends, friendliness, aggression, and failure compared to norms. Besides, there were no torso-anatomy references.Female, some months after surgery, showed fewer aggression, self-negativity, negative emotions, torso-anatomy contents, dreamer’s success, and more good fortune compared to norms. Women’s self-perception appears less frightened, and dominated by negative emotions, maybe suggesting a good self-restructuring which could be tied to the ordeal of overcoming cancer.Yet the complete absence of body-related topics in women’s dreams both at T0 and T1 could reflect clear neglect about the body-shape change.T0 and T1 in males showed, substantially, no significant differences, whereas women at T0 showed more bodily misfortune, aggression, and familiar settings. According to Domhoff’s perspective, the presence of an abundance of family members and settings and increased misfortunes could be related to a dreamer’s maladjustment problems. As we previously said, these concerns seemed to be better managed some months after surgery.It seems possible that males were less worried about the health problem from the beginning, and women showed more initial difficulties that seemed to be resolved after 4–6 months after surgery.As explained by Revonsuo’s (2000) perspective and Ernest Hartmann’s (1996) theory, the function of dreaming is to “contextualize a dominant emotion of the dreamer”, making “connections more broadly than waking in the nets of mind” ,75. All Some limits in our study should be underlined. Difficulties in recruitment in this research field resulted in a small sample of patients and consequent limited statistical analysis power. Additionally, the wider SD we obtained at T1 was because we tried to reevaluate the patients during medical follow-up visits that were differently distributed in a large period of time. It was impossible to reach the patients during an additional visit. This could have missed possible additional changes in the body perception at 4 and 6 months after the amputation.We also did not consider the possible prosthesis reconstruction, which could affect some variables mostly regarding the subjective sensation of a possible return to “integrity”. Some of the subjects in our study refused prosthesis, some were not eligible, and some of them were not in the process yet, so we did not have enough data to collect and analyze.In addition, considering the persistence, in half of the patients, of the amputated limb in their dreams, it would be important to further re-test the patients and plan an extended follow-up.The analysis of dream content, which could reveal the expression of inner self-perception through a novel analysis method, could significantly improve psycho-oncologists’ and clinicians’ ability to support their patients during their therapeutic course. The persistence of an intact self-image, even 4–6 months after surgery, in some of our patients’ dreams may suggest an ongoing plasticity process that has to be better evaluated to implement a timely intervention. Indeed, providing proper psychological support is essential in patients who have to face important challenges in self-perception and possible significant changes in the quality of their lives.


Pain is a major symptom in patients with rheumatoid arthritis (RA). In early RA, pain is usually due to synovitis, but can also persist despite effective anti-inflammatory treatment. The objective of this study was to investigate the pain course over time and predictors of unacceptable pain and unacceptable pain with low inflammation, in patients with early RA.An inception cohort of 232 patients with early RA, recruited in 1995–2005, was followed in a structured programme for 5 years. Pain was assessed using a visual analogue scale . Unacceptable pain was defined as VAS pain > 40 based on the patient acceptable symptom state (PASS) and low inflammation as CRP < 10 mg/l. Baseline predictors of unacceptable pain were evaluated using logistic regression analysis.Pain improved significantly during the first 6 months, but then remained basically unchanged. Thirty-four per cent of the patients had unacceptable pain 5 years after inclusion. Baseline predictors of unacceptable pain after 5 years were lower swollen joint counts [odds ratio (OR) 0.71 per standard deviation  0.51–0.99)] and higher VAS for pain and global assessment of disease activity. Unacceptable pain with low inflammation after 5 years was negatively associated with anti-CCP antibodies [OR 0.50 (95% CI 0.22–0.98)].Over one third of the patients had unacceptable pain 5 years after inclusion. Lower swollen joint count was associated with unacceptable pain at 5 years. The results may be explained by the positive effects of treatment on pain related to inflammation. Non-inflammatory long-lasting pain appears to be a greater problem in anti-CCP-negative patients.The online version contains supplementary material available at 10.1186/s13075-021-02550-7. Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease characterized by inflammation of the joints, resulting in pain, stiffness and destruction of articular bone and cartilage. With more extensive treatment with disease-modifying anti-rheumatic drugs (DMARDs) in recent years, the average disease course, measured using patient-reported outcomes (PROs) , clinicaPainful arthritis is, in part, due to effects of inflammatory cytokines, which activate nociceptors in the synovium . It has Pain is a debilitating symptom and has been associated with reduced health-related quality of life and increased disability , 13, andIn a recent study, pain trajectories in RA patients were investigated in 3 different cohorts. A low pain trajectory was identified, with patients who had low pain during the whole follow-up time, but only in the cohort of early RA patients, suggesting that early interventions are of importance for pain management . By findThe aims of this study were to examine (1) the course of pain and proportion of unacceptable pain during the first 5 years of early RA, (2) predictors of change in pain, and (3) predictors of unacceptable pain, overall and with low inflammatory activity.An inception cohort of patients with early RA consisting of 233 patients from the city of Malmö, Sweden, recruited in 1995–2005 with a symptom duration ≤ 12 months at inclusion was investigated , 23. PatPatients were followed in a structured programme with examination and collection of data at inclusion, 6 months and 1, 2 and 5 years. There was no pre-specified protocol for pharmacotherapy—all patients were managed according to standard care. PROs and disease activity measures were collected at every follow-up visit. A visual analogue scale  was used for assessing pain, as well as the patients’ global assessment of disease activity (PGA). The number of swollen and tender joints (out of 28) was assessed by the same rheumatologist for all patients at all visits. Disability was evaluated using the Swedish validated version of the Stanford Health Assessment Questionnaire (HAQ) . For disAs markers of ongoing inflammation, the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were measured, using standard methods at the Department of Clinical Chemistry at Malmö University Hospital. At inclusion, all patients were tested for rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) seropositivity, using standard ELISA methods at the immunology laboratories of the University Hospitals in Malmö and Lund. IgM RF was analysed using ELISA, which was calibrated against the World Health Organization RF reference preparation. Anti-CCP antibodies were analysed using the Quanta Lite CCP IgG ELISA .Unacceptable pain was defined as VAS pain > 40 mm, based on the patient acceptable symptom state (PASS) , which iIBM SPSS statistics version 26 was used for statistical analyses. The development of pain over time was assessed using descriptive statistics, and the change in pain between every visit was evaluated using the paired t test. To determine the normality distribution of data, the Shapiro-Wilk test was used. Confidence intervals for the proportion of patients with unacceptable pain were computed using the Wald method with normal approximation. If observed cases were < 5 mid-P exact intervals were used. Potential baseline predictors of unacceptable pain, and of unacceptable pain with low inflammation, were assessed using univariate and multivariate logistic regression analysis. Results were presented as odds ratios (OR) with 95% confidence intervals (CI). Continuous variables were analysed per standard deviation and were tested for linearity to the logit of the dependent variable. As a secondary analysis, predictors of unacceptable pain with high inflammation were also assessed. Since the method for measuring CRP during part of the period was not highly sensitive and did not include any values below 9, CRP values were analysed by groups of CRP < 9 mg/l and the two highest quartiles, with the first group as reference. Variables with a p value < 0.10 were eligible for multivariate analyses and were assessed for bivariate correlations, using Spearman’s rank correlation test. In the case of collinearity (bivariate correlation between covariates with r > 0.3), only the covariate with the strongest association with the outcome variable was included in the multivariate logistic regression model. Sensitivity analyses were also performed with adjustment for year of inclusion and place of practice (university vs private).Baseline predictors of pain over time were assessed using mixed model analysis, using all VAS pain values at inclusion and follow-ups at 6 months, 1, 2 and 5 years. Differences in pain at baseline by baseline characteristics were estimated as the intercept, based on the regression line. Mean differences in pain over time and differences in change of pain per month were estimated.A total of 232 patients with early RA (median symptom duration 7 months (interquartile range: 5–10)) were included in the study. All the patients fulfilled 1987 ACR criteria for RA. Due to missing data for some parameters , the 2010 ACR/EULAR criteria could not be fully evaluated, but at least 88% (204/232) of the patients fulfilled these criteria at inclusion. The 5-year follow-up was attended by 179 patients. Patient characteristics at inclusion, 6 months and 1, 2 and 5 years are shown in Table The mean VAS pain was 41.2 at inclusion and decreased significantly to 32.3 at the 6-month visit, but then remained more or less unchanged during the rest of the follow-up period Fig. . The meaThe proportion of patients with unacceptable pain at inclusion was 49.1% and decreased to 30.1% during the first year. After that, the fraction of patients with unacceptable pain was essentially unchanged over time Fig. . At inclBaseline predictors of unacceptable pain at 6 months and 1, 2 and 5 years from inclusion were identified. Baseline treatment with methotrexate was similar in patients with and without unacceptable pain at each of the follow-up visits  still had unacceptable pain. In univariate analysis, baseline predictors of unacceptable pain at 5 years were, again, higher VAS pain and VAS PGA Table . There wTo investigate pain patterns indicative of a non-inflammatory mechanism, baseline predictors of unacceptable pain with low inflammation were also identified. Patient characteristics at baseline in patients with unacceptable pain plus low inflammation at 6 months and 1, 2 and 5 years are shown in Additional file At the 5-year follow-up, 40 patients (22.5%) had unacceptable pain with low inflammation. Anti-CCP negativity was the only significant baseline predictor of this state in both univariate and multivariate analysis , ESR and CRP in descending order, with the strongest predictor being PGA Table . For eacIn this study, we found that approximately one third of patients with RA have unacceptable pain up to 5 years after diagnosis and that nearly two thirds of these patients have pain despite low inflammatory activity. Pain improvement was only significant between inclusion and the 6 month-visit, and average pain was thereafter essentially unchanged over time. Several baseline variables, including PROs , and clinical outcomes like low SJC and low grip force, as well as female sex and low age, predicted unacceptable pain. Out of these associations, those with VAS for pain and PGA were consistently significant over time, and both low SJC and high VAS PGA remained significantly associated with unacceptable pain in the multivariate analyses at 5 years. Unacceptable pain with low inflammatory activity was also predicted by low baseline inflammatory parameters and anti-CCP negativity. In mixed model analysis, high baseline PGA VAS, HAQ and DAS28 were particularly associated with increased pain at baseline, but also with greater improvement in pain over time.Several recent studies have reported that although pain outcome has improved in more recent years since the introduction of more extensive anti-rheumatic treatment and biologic therapy, there is still a group of patients with persistent pain , 4, 7. TWorse baseline PROs have previously been associated with increased pain levels later during the disease course . For exaDiscrepancies between PROs and objective disease activity measures regarding their importance for pain have been reported earlier , 37. FurThe uncoupling between pain and inflammation supports that non-inflammatory mechanisms contribute to pain in RA. This concept is supported by the association between unacceptable pain and low swollen joint count found in the present study. Furthermore, the prevalence of concomitant fibromyalgia in RA has been reported to be up to 25% , as compSome limitations of the present study should also be noted. Data on comorbidities before RA diagnosis were not available, and therefore the effects of other prevalent diagnoses affecting pain, e.g. concomitant fibromyalgia, depression and osteoarthritis, on the results cannot be excluded. Misclassification of individuals with primary fibromyalgia as RA in this study is however unlikely, as even patients with unacceptable pain and low inflammation at follow-up had active disease at inclusion, with median SJCs above 6, and all patients fulfilled the 1987 RA classification criteria at inclusion. The small number of patients was another limitation of the study, as it affects the statistical power, especially for the analyses of unacceptable pain with low inflammation. It would also have been interesting to investigate predictors of unacceptable pain with the strict definition of low inflammation, but the number of patients in this subset was too small. This would be of interest to study in a larger cohort. The data-driven, hypothesis-free approach for selecting covariates for the multivariate models may not be optimal. Other methods, e.g. selection of covariates based on a priori hypothesis, may be useful, in particular in larger samples. Moreover, the majority of patients were included before the practice of treat to target was implemented and before early treatment with biologic DMARDs was standard of care in severe cases, and the results of this study might therefore not be fully applicable to patients diagnosed in the more recent period. However, studies of more recent cohorts demonstrate that pain remains a major problem in patients with RA –6, 8. FiThe strengths of this study include a systematic longitudinal follow-up of patients from a defined period of time and a defined catchment area. Therefore, there should not be a major risk of selection bias, and the results could be generalized to patients with RA seen in clinical practice. Furthermore, all joint assessments were performed by the same rheumatologist for all patients, using a structured protocol. Finally, the definition of unacceptable pain is a common and validated measure, which makes it possible to compare the results of this study to other reports.More than one third of patients with new-onset RA suffer from long-lasting unacceptable pain, and the majority of these patients have pain despite the low inflammatory activity. This indicates large unmet needs in RA pain management and highlights that non-inflammatory mechanisms contribute substantially to the pain spectrum. Worse PROs at inclusion, i.e. HAQ, VAS pain and VAS PGA, were associated with unacceptable pain and with a greater burden of pain over time. Furthermore, non-inflammatory long-lasting pain appears to be a greater problem in anti-CCP-negative patients. Future studies should investigate how to improve pain management for such patients, for example by encouraging more effective coping strategies. Patients with less inflammatory disease at baseline, in the form of low swollen joint count, had an increased risk of unacceptable pain at 5 years. This may be explained by the positive effects of treatment on pain related to inflammation.Additional file 1:. Baseline characteristics in early RA patients with or without unacceptable pain at follow-ups.Additional file 2:. Sensitivity analysis – baseline predictors of unacceptable pain in early RA.Additional file 3:. Baseline characteristics in patients with or without unacceptable pain and low inflammation at follow-ups.Additional file 4:. Sensitivity analysis – baseline predictors of unacceptable pain with low inflammation in early RA.Additional file 5:. Baseline predictors of unacceptable pain and high inflammation – 6 months, 1, 2 and 5 years after diagnosis.Additional file 6:. Baseline characteristics in patients with or without unacceptable pain and high inflammation at follow-ups.


Background: Chronic postsurgical pain (CPSP) and associated long-term opioid use are major public health concerns.Aims: The Toronto General Hospital Transitional Pain Service (TPS) is a multidisciplinary, hospital-integrated program developed to prevent and manage CPSP and support opioid tapering. This clinical practice–based study reports on preliminary outcomes of the TPS psychology program, which provides acceptance and commitment therapy (ACT) to patients at risk for CPSP and persistent opioid use.Methods: Ninety-one patients received ACT, whereas 252 patients did not (no ACT group). Patient outcomes were compared for the two groups at first and last TPS visits. Pain, pain interference, sensitivity to pain traumatization, pain catastrophizing, anxiety, depression, and opioid use were analyzed using two-way  analyses of variance (ANOVAs).Results: Patients referred to ACT were more likely to report a mental health condition preoperatively (P < 0.001), had higher opioid use (P < 0.001) at the first postsurgical visit, and reported higher sensitivity to pain traumatization (P < 0.05) and anxiety (P < 0.05) than the no ACT group at both time points. Both groups showed reductions in pain, pain interference, pain catastrophizing, anxiety, and opioid use by the last TPS visit (P < 0.05). The ACT group demonstrated greater reductions in opioid use and pain interference and showed reductions in depressed mood (P = 0.001) by the end of treatment compared to the no ACT group.Conclusion: Preliminary outcomes suggest that ACT was effective in reducing opioid use while pain interference and mood improved. Furthermore, they are typically offered very little medical or behavioral guidance to support opioid weaning,12 given the general expectation that postsurgical pain will resolve and pain medication use will naturally taper in parallel. However, between 5% and 70% of surgery patients develop chronic postsurgical pain (CPSP), depending in part upon the surgical procedure.13 Moreover, 3% and 0.4% of previously opioid-naïve patients continue to use opioids 3 months7 and 1 year after major surgery, respectively, likely due to persistent postsurgical pain.6Public health concerns related to high-dose, long-term opioid use for the treatment of persistent pain have reached a fever pitch. These concerns are fueled by the lack of evidence for the effectiveness of opioids in adequately treating or alleviating many chronic pain conditions,12 Patients taking a selective serotonin reuptake inhibitor (SSRI) or a benzodiazepine prior to surgery to treat depression or anxiety have been identified as having the highest risk of persisting on opioids following major surgery.14 The combination of postsurgical pain, disability, and continued psychological symptoms can be overwhelming for patients in the early recovery period. Thus, a concerted effort must be made to address depression and anxiety in the months after surgery because they have the potential to amplify pain, pain interference, and opioid use.Recent U.S. national guidelines for managing postsurgical pain have emphasized that opioids should not constitute a stand-alone treatment for postoperative pain and should be combined with nonpharmacological approaches to prevent long-term opioid use.15 The TPS provides physician-guided opioid medication management and tapering, as well as opioid-sparing, nonopioid pharmacotherapy . The TPS also offers behavioral interventions grounded in Acceptance and Commitment Therapy (ACT) that are tailored to the postsurgical population and address pain education, pain coping, pain interference, and mood and anxiety concerns.16The Toronto General Hospital has developed an innovative Transitional Pain Service (TPS) that uses multidisciplinary methods to prevent and manage CPSP.18 and has been rated as having strong research support in the treatment of chronic pain by Division 12 of the American Psychological Association.19 Systematic review has suggested that ACT is particularly effective in terms of reducing distress and improving functioning, particularly physical functioning, in people living with long-term pain.20 Acceptance-based interventions have also been shown to reduce pain intensity21; however, there are indications that acceptance-based interventions that focus on mindfulness mediation training  may be associated with greater reductions in pain intensity than ACT interventions.22 This is consistent with the theoretical framework of ACT for the treatment of chronic pain, which does not emphasize reductions in pain intensity per se, because single-minded pursuit of pain relief is considered ineffective and unworkable once pain has become entrenched.18 Instead, ACT intervention is focused on fostering committed engagement with valued life activities, while promoting mindfulness and acceptance of difficult private experiences, such as pain. This is consistent with the sometimes controversial perspective that multidisciplinary treatments for chronic pain, including medication management, are most effectively targeted at reducing pain-related distress and disability, rather than reducing pain intensity.23 At the TPS, psychology services consist of individual and group sessions of ACT led by a clinical psychologist and supervised trainees who help patients to develop behavioral skills that make pain more manageable and thus support opioid tapering, so that patients can achieve “a balance between the benefits and potential harms of opioids” (p. 2098).23ACT has garnered significant research support as an effective behavioral chronic pain intervention in a relatively short amount of time15 To our knowledge, this is the first hospital-integrated, comprehensive, long-term postsurgical pain management program of its kind. Thus, little data are available on clinical outcomes of postsurgical patients who receive psychological support to help them manage complex and persistent postsurgical pain, opioid use, and psychosocial symptoms.The TPS psychology service provides proactive, timely support in a multidisciplinary setting to outpatients with complex postsurgical pain for up to 6 months after surgery. TPS patients are flagged for presurgical psychosocial or mental health problems, chronic opioid use, and/or pre-existing chronic pain in order to ensure that an intensive intervention is provided to patients who are at the highest risk for developing CPSP and persistent high-dose opioid use.We undertook analyses on preliminary data from the TPS based on patients’ usage of psychological services, specifically examining changes in pain, pain interference, sensitivity to pain traumatization, pain catastrophizing, anxiety and depressive symptoms, and opioid use throughout the duration of their TPS treatment. We hypothesized significant decreases in pain, opioid use, pain interference, pain catastrophizing, sensitivity to pain sensitization, and anxiety and depressive symptoms in patients who received psychology services. Given that TPS psychology services were provided to patients with a high risk of developing CPSP and long-term, high-dose opioid use, we also explored pain, psychosocial outcomes, and opioid use in patients who did not receive any psychology treatment to examine the extent of improvement between the two groups.The study was reviewed and approved by the research ethics boards of Toronto General Hospital  and York University . All patients provided informed written consent to participate.n = 89, 23.30%); (2) referred by the Acute Pain Service (APS) after surgery and followed by the TPS as surgical inpatients, with continued care as outpatients after hospital discharge ; or (3) referred by surgeons or primary care physicians to the TPS outpatient clinic when pain persisted after postsurgical hospital discharge . Two postsurgical patients self-referred to the TPS. Overall, 364 patients attended the TPS clinic for post–hospital discharge visits after major surgery . Patients who attended the TPS and received treatment for chronic pain unrelated to major surgery were excluded from this study (n = 18).Data were collected on 382 patients  attending the TPS clinic between April 2014 and November 2016. Patients were referred to the TPS by one of three care pathways: (1) referred and followed prior to their surgery date due to risk factors for postsurgical pain and followed as TPS outpatients after surgery  or any one or more of the following: (1) pre-existing chronic pain; (2) physician- or nurse-assessed clinical depression, anxiety, and/or problematic opioid use; (3) physician or nurse clinical judgment that the patient was demonstrating marked difficulty coping with postsurgical pain, compared to the average postsurgical patient who has undergone an equivalent procedure; or 4) daily opioid use higher than expected and/or persisting at high doses for longer than expected in the postsurgical recovery period, with possible psychological barriers to opioid tapering. Because this was not a controlled trial, referral criteria were not strictly operationalized but were based on clinical judgment.n = 91) were classified as belonging to the ACT group. Postsurgical patients who did not receive any psychology services were classified as belonging to the no ACT group (n = 252). Twenty-one patients were assessed by psychology services but did not elect to participate in ACT sessions. These 21 patients were excluded from the analyses in order to avoid confounding the study groups.Patients who received one or more ACT intervention sessions after postsurgical hospital discharge  that aim to control pain, including taking pain medication; and engage in activities (represented in the “toward moves” quadrant) that nurtured their connections with loved ones and fulfilled their values  with 10 years of experience using ACT and/or one of two supervised PhD-level clinical psychology graduate students . Treatment was primarily delivered in one-on-one sessions, with a minority of patients attending a pilot series of group sessions. All sessions followed an ACT treatment protocol designed to reduce struggle against difficult inner experiences (such as pain) while, at the same time, fostering long-term patterns of behavior aimed at building a rich and rewarding life.T matrix .24 PatieDemographic and clinical health information  was collected by nurses in the surgical pre-admission clinic as part of routine clinical care by (1) use of a standardized pre-admission interview and (2) review of the patient’s hospital-based electronic medical record. Health information from the pre-admission visit note was later abstracted from the electronic medical record by the research team. Patients were asked to complete questionnaire packages at pre-surgery, post-surgery in-hospital, and post-hospital discharge outpatient TPS visits. For the purposes of analyses, we used the first and last post-hospital discharge outpatient questionnaire data. The questionnaire package included the following inventories.29 is a 16-item scale that assesses current, least, average, and worst pain intensity using a numeric rating scale (NRS) of 0 (no pain) to 10 (pain as bad as you can imagine). It contains seven pain interference subscales that measure how pain interferes with various daily activities including general activity, walking, work, mood, enjoyment of life, relations with others, and sleep. Patients rate each aspect of pain interference using an 11-point NRS . Pain interference is measured as a mean of the seven subscales, with higher scores meaning that pain interferes to a higher degree in the patient’s functioning. The pain interference subscale has good internal consistency (α = 0.80) in clinical samples.30 Internal consistency of the BPI-SF pain interference subscale for the present study was 0.94.The Brief Pain Inventory–Short Form (BPI-SF)31 is a 12-item, self-report scale that measures vulnerability to developing anxiety-related cognitive, emotional, and behavioral reactions to pain that resemble symptoms of a traumatic stress reaction . Each item is rated on a five-point rating scale using the following response options: 0 = not at all true; 1 = slightly true; 2 = somewhat true; 3 = very true; and 4 = entirely true. Total scores (sum of 12 items) range from 0 to 48, with higher scores indicating higher levels of sensitivity to pain traumatization. The SPTS-12 has a one-factor structure, good convergent and divergent validity, and excellent internal consistency (0.84–0.92) in community and clinical samples.32 The SPTS-12 predicts pain intensity and pain interference post–hospital discharge in patients who have undergone major surgery.33 Internal consistency of the SPTS-12 for the present study was 0.92.The Sensitivity to Pain Traumatization Scale–12 (SPTS-12)34 is a 13-item scale that measures catastrophic thinking in relation to pain. Each item is rated on a five-point rating scale using the following response options: 0 = not at all; 1 = to a slight degree; 2 = to a moderate degree; 3 = to a great degree; and 4 = all the time. The PCS yields a total score and three subscale scores assessing rumination , magnification , and helplessness . The PCS has demonstrated good convergent and divergent validity and excellent internal consistency (α = 0.95) in a sample of chronic pain patients.35 Internal consistency of the PCS for the present study was 0.96.The Pain Catastrophizing Scale (PCS)36 is a widely used 14-item scale that assesses symptoms of anxiety  and depression  among medical inpatients, outpatients, and in the general population. For each item, the patient is asked to select from among five possible responses  the one that best describes how they have been feeling over the past week. Suggested clinical cutoffs for the HADS are 8–10 for mild, 11–15 for moderate, and ≥16 for severe depression or anxiety.37 The HADS has demonstrated good internal consistency in clinical samples .37 Internal consistencies of HADS-A and HADS-D for the present study were 0.82 and 0.83, respectively.The Hospital Anxiety and Depression Scale (HADS)39 and the conversion methods used by physicians and nurses at UHN. Values obtained at the first and last outpatient TPS visits for all outcomes were included in the analyses to examine changes over the duration of TPS involvement.The amount of opioids used in a 24-hour period was recorded in the medical charts by TPS physicians at each patient visit (including deviations from prescribed amounts) and abstracted from the medical record. Opioid use was calculated as total morphine equivalent dose (MED) per 24 hours based upon the scientific literatureData were transformed when assumptions of normality were not met, as was the case for MED (log transformed), depressive symptoms (log transformed), and pain catastrophizing (square root transformed).40 Wilk’s Lambda values (^) were used to interpret the percent variance in dependent variables not accounted for by independent variables.Age was analyzed using one-way analysis of variance (ANOVA). Preoperative MED, number of weeks of TPS attendance, number of medical visits, and number of comorbidities were analyzed using a Kruskal-Wallis H test with group  as the independent variable. Sex, preoperative chronic pain, preoperative opioid use, preoperative mental health conditions, and preoperative mental health medications were analyzed using Pearson’s Chi-squared tests of likelihood followed by inspection of standardized residuals within cells to determine the pattern of significance among cells. Separate Chi-squared tests were used to examine differences in TPS discharge opioid status , between ACT and no ACT groups according to preoperative opioid status . Clinical outcomes were analyzed by two-way ANOVA using group  and time  as factors and current pain, opioid use, pain interference, sensitivity to pain traumatization, pain catastrophizing, anxiety symptoms, and depressive symptoms as dependant variables. Significant interaction effects were followed by tests of simple main effects. Partial eta-squared  = 8.08, P = 0.005, showing that the ACT group was significantly younger than the no ACT group. Chi-square test indicated a significant association between group and preoperative mental health condition, χ2(1) = 17.38, P < 0.001: Participants in the ACT group were significantly more likely to have reported a mental health problem at their pre-admission visit  than those in the no ACT group. Fifty percent of patients in the ACT group had been taking medications such as SSRIs and anxiolytics preoperatively for mental health conditions compared to 28.5% in the no ACT group. The Kruskal-Wallis H test showed that there was a significant difference in duration (weeks) of TPS involvement between groups, χ2(1) = 40.69, P < 0.001 , and number of medical visits, χ2(1) = 51.02, P < .001 , with the ACT group having greater weeks of involvement and number of medical visits with the TPS. Sex, number of comorbidities, preoperative chronic pain condition, preoperative mental health medications, preoperative opioid use, and preoperative MED did not differ significantly between the groups. Data on numbers of ACT and no ACT group patients using opioids at TPS discharge according to preoperative opioid use are presented in 2(1) = 4.37, P < 0.05, for preoperatively opioid-naïve patients: A greater proportion of preoperative opioid-naïve patients in the ACT group were completely weaned off opioids (65.4%) compared to the no ACT group  = 23.10, P < 0.001, ANOVA revealed a significant main effect of time, FPS visit . The ACT = 52.74, P < 0.001,  = 6.07, P < 0.05,  = 32.98, P < 0.001,  = 20.34, P < 0.001, ANOVA revealed a significant main effect of time, FCT group . Simple  = 4.63, P < 0.05, ANOVA revealed a significant main effect of group, Fe points . = 13.18, P < 0.001, ANOVA revealed a significant main effect of time, FPS visit . = 5.52, P < 0.05,  = 5.13, P < 0.05, ANOVA revealed a significant main effect of group, FPS visit . = 12.65, P < 0.001,  = 4.07, P < 0.05,  = 10.98, P = 0.001,  = 2.03, P = 0.16, ANOVA revealed a significant main effect of time, FPS visit  but not  = 5.17, P < 0.05,  = 74.67, P < 0.001,  = 22.35, P < 0.001,  = 18.18, P < 0.001, P < 0.001). In contrast, the simple main effect of group was not significant at the last TPS visit, indicating that the ACT group’s MED had reduced to the level of the no ACT group by the last TPS visit  = 63.89, P < 0.001,  = 12.74, P > 0.001, ANOVA revealed significant main effects of group, FPS visit . Simple PS visit .10.1080/This study reports on treatment outcomes for two groups of postsurgical patients treated by a novel, multidisciplinary, transitional pain service in which one group received an ACT-based behavioral pain management intervention and the other did not. The results indicate that both groups improved over the course of the study, showing significant decreases in pain intensity, pain interference, pain catastrophizing, anxiety symptoms, and opioid use by the time of the last TPS visit. Furthermore, the patients who participated in a brief (mean of five sessions) ACT-based pain psychology program in addition to medication management by pain specialist physicians demonstrated significantly greater reductions in opioid use, pain interference, and depressed mood than patients who received physician-guided treatment alone. Differences in time involved with the TPS between ACT and no ACT groups help contextualize the differing needs of complex postsurgical patients. Patients in the ACT group likely had increased needs for follow-up care over time, because their symptoms may have persisted or intensified over a longer period after surgery requiring continued follow-up. Findings of this study should be interpreted with caution due to the inability to attribute symptom improvements among patients in the ACT group mainly to the ACT intervention, because these patients also received significantly more physician-guided care.41 However, by the last TPS visit, daily opioid consumption did not differ significantly between the groups, suggesting that the ACT group was able to taper their opioid use by a greater amount. In addition, pain interference decreased to a greater extent in the ACT group. Moreover, only the ACT group showed significant reductions in depressive symptoms by the last TPS visit. Taken together, the results suggest that a higher-risk group of patients who learned the ACT approach to behavioral pain management were able to wean further off opioid medications, while experiencing improvements in mood and less interference from pain in important daily life activities, in comparison to the lower-risk, no ACT group. The results of the present study provide preliminary support for ACT-based intervention targeting patients after surgery who are at risk of CPSP and long-term, high-dose opioid use.It is important to note that these data were obtained in the course of routine practice in the Transitional Pain Service operating in a hospital setting, rather than in the idealized and rigorously controlled conditions of a randomized controlled trial that limit external validity. Accordingly, the present findings should be generalizable to real-world clinical care settings in many hospitals around the globe in which patients have complex pain histories, a variety of mental health conditions, and often a history of presurgical, chronic opioid use. As an investigation of naturalistic clinical care, there were significant differences between the two groups at baseline. Patients who were referred to the ACT-based pain psychology program had significantly higher daily opioid use at their first TPS visit, as well as more anxiety, higher sensitivity to pain traumatization scores, and a greater prevalence of preoperative mental health conditions. Thus, the ACT group was at higher risk of persistent pain, pain-related disability, depression, and long-term, high-dose opioid use.43 Meanwhile, concerns continue to rise with regard to the risks of long-term, high-dose opioid use44 and dose escalation triggered by postsurgical opioid prescribing practices with little in the way of opioid tapering assistance.12 The present study provides preliminary evidence that there is a potentially powerful role for behavioral interventions in supporting opioid tapering among complex pain patients who have undergone major surgery. In addition to the ACT group’s greater mean reductions in daily opioid consumption at TPS discharge, a greater percentage of opioid-naïve ACT group patients tapered their opioid use to zero in comparison to the no ACT group  and atypical antidepressants as adjunct, opioid-sparing medications for postsurgical neuropathic pain, though perhaps not at adequate doses for mood effects. The behavioral activation component of the ACT matrix intervention, which emphasizes engaging in meaningful activities, is designed to alleviate depression at the same time that functioning improves.Surgical patients who are highly distressed and anxious are more likely to develop persistent postsurgical painThere are several limitations to the present study. First, this research was observational in nature without random assignment to treatment groups; thus, our results may be subject to confounding by treatment indication. However, as described above, the ACT group was more severe with respect to risk factors for postsurgical pain at baseline and thus would be expected to have poorer outcomes—that is, the selection bias observed in the present study would bias our analyses toward the null hypothesis of no difference in outcomes between groups or better outcomes for the no ACT group. The fact that we nonetheless observed decreases in pain, pain interference, pain catastrophizing, anxiety symptoms, and opioid use with outcomes comparable in both the ACT and no ACT group suggests that the strength of effect of the ACT intervention outweighed confounding in the opposite direction. Of particular note, our findings that the ACT group demonstrated greater reductions in depression scores, opioid use, and pain interference than the no ACT group speak to the strength of the ACT intervention.13 and long-term presurgical opioid use, we may have observed greater effect sizes and additional significant effects of psychological treatment on reducing poor postsurgical outcomes.Another limitation of the present study is that our relatively small sample size precluded full multivariate adjustment and reduced our power to detect underlying treatment effects. If we had sufficient power to control for higher rates of perioperative risk factors for CPSP (such as preexistent chronic pain)13 and extended opioid use.6 Due to small numbers of individuals with each surgery, we lacked sufficient power to run subgroup analyses of differential responses to psychological intervention and TPS treatment overall. Furthermore, heterogeneity of surgical intervention contributes to reduced power to detect potentially real treatment effects and accordingly we are planning randomized controlled trials with intent-to-treat analyses within a given high-risk surgical population.The patients in this study underwent a heterogenous set of surgical interventions typical of hospital settings, which may limit the precision of our findings. Different surgical modalities are known to yield different rates of CPSPFinally, all follow-up comparisons were based on group differences at the conclusion of TPS visits, a clinically relevant time point where specialist treatment is discontinued and patients are transitioned back to their primary care physicians. A drawback of this approach is that differences in treatment duration observed between the ACT and no ACT groups represent a confounding variable in this study. Thus, the extent to which the no ACT group would have achieved additional reductions in opioid weaning, pain interference, and depressive symptomology given an equivalent follow-up time is not known. It is also not known whether participation in the ACT treatment protocol increased patient engagement with the service, leading to an increased willingness to attend additional appointments, or whether distressed, yet adherent, patients were more drawn to the option of ACT treatment.To address these limitations, we aim to run additional analyses with an increased sample size, allowing sufficient power for multivariate adjustment for confounding by indication, follow-up duration, and surgery type subgroups.This study reports promising preliminary outcomes from a multidisciplinary transitional pain service that addresses a substantial gap in treatment for patients who have undergone major surgery and are at high risk of developing CPSP and prolonged, high-dose opioid use. The Transitional Pain Service bridges the gap between in-hospital, acute postsurgical pain management and specialized care for chronic pain that is often long delayed and difficult to access. Patients presenting with complex pain problems after surgery receive timely, state-of-the-art, multidisciplinary intervention that provides them with a full repertoire of options for managing their pain in order to reduce reliance on opioid medication. Patients living with pain after surgery understandably want pain relief and need assurance that tapering their opioid medication will not result in more pain, disability, and suffering. The Transitional Pain Service model aims to address these issues in the critical postsurgical period, as part of a new generation of solutions for pain management that address the current public health challenges associated with pain-related high-dose, long-term opioid use.