Interdisciplinary pain rehabilitation for patients with Ehlers-Danlos syndrome and hypermobility spectrum disorders.

OBJECTIVE: Chronic pain is a common manifestation of Ehlers-Danlos syndrome and hypermobility spectrum disorders; thus it is often suggested that patients undergo generic interdisciplinary pain rehabilitation, despite there being little evidence to support this decision. The aim of this study is to examine the effectiveness of standard rehabilitation programmes for chronic pain on patients with Ehlers-Danlos syndrome and hypermobility spectrum disorders, compared with patients with other chronic pain disorders. SUBJECTS: Data, collected between 2008 and 2016, were extracted from a Swedish national registry. The patient data comprised of 406 cases with Ehlers-Danlos syndrome or hypermobility spectrum disorders, 784 cases with a whiplash-related diagnosis, 3713 cases with diagnoses relating to spinal pain, and 2880 cases of fibromyalgia. METHODS: The differences between groups on key outcome measures from pre- to 1-year follow-up after interdisciplinary pain rehabilitation were analysed using linear mixed effects models. Sensitivity analysis in the form of pattern-mixture modelling was conducted to discern the impact of missing data. RESULTS: No significant differences were found in improvements from pre- to 1-year follow-up for patients with Ehlers-Danlos syndrome or hypermobility spectrum disorder compared with other diagnostic groups regarding measures of health-related quality of life, mental health, or fatigue. At follow-up, differences in pain interference (d = -0.34 (95% confidence interval [95% CI] -0.5 to -0.18)), average pain (d = 0.22 (95% CI 0.11-0.62)) and physical functioning (d = 2.19 (95% CI 1.61-2.77)) were detected for the group with spinal-related diagnoses in relation to those with EDS/HSD, largely due to pre-treatment group differences. Sensitivity analysis found little evidence for missing data influencing the results. CONCLUSION: This study suggests that patients with Ehlers-Danlos syndrome/hypermobility spectrum disorders may benefit from inclusion in an interdisciplinary pain rehabilitation programme.

Acceptance and Fear-Avoidance Mediate Outcomes of Interdisciplinary Pain Rehabilitation Programs at 12-Month Follow-Up: A Clinical Registry-Based Longitudinal Cohort Study from the Swedish Quality Registry for Pain Rehabilitation (SQRP).

Background: Factors that influence outcomes of interdisciplinary pain rehabilitation programs (IPRP) are poorly known. It is unclear how outcomes are influenced by pain intensity, psychological distress, and coping strategies. Aim: This clinical registry-based longitudinal cohort study has three aims: 1) to determine the relative importance of pain intensity, psychological distress, acceptance, and fear-avoidance for changes in three outcomes of IPRP at 12-month follow-up; 2) to investigate whether the effects of pain intensity and psychological distress on the three outcomes are mediated via acceptance and fear-avoidance; and 3) to determine whether sex is a moderator. Methods: This study uses Patient-Reported Outcome Measures (PROMs) from specialist units reporting data (2008-2016) to the Swedish Quality Registry for Pain Rehabilitation (SQRP). Adult chronic pain patients (N = 1991) answered the PROMs (background, pain, psychological distress, coping, participation, and health-related quality of life (HRQoL)). Partial Least Squares Structural Equation Modelling (PLS-SEM) was used to explore the aims. Results: Changes in acceptance (ß:0.424-0.553; all P<0.001) were the strongest predictor of the three outcomes (changes in life control, interference, and HRQoL) at 12-month follow-up. The next strongest predictor was baseline acceptance (ß: 0.177-0.233; all P<0.001) and changes in fear-avoidance (ß: -0.152- -0.186; all P<0.001). Baseline pain intensity and psychological distress showed weak positive associations. Their effects on the three outcomes were mediated via acceptance aspects. Sex was not a moderator. Discussion and Conclusion: Acceptance aspects (baseline and changes) were important predictors of IPRP outcomes. Changes in fear-avoidance were also important although to a lesser degree. Some of the effects of pain intensity and psychological distress on outcomes were mediated via acceptance at baseline. Future PLS-SEM analysis of real-world IPRP should include more potential mediators (eg, catastrophizing and more facets of psychological flexibility and fear-avoidance) and the components of IPRP.

Catastrophizing and acceptance are mediators between insomnia and pain intensity-an SQRP study of more than 6,400 patients with non-malignant chronic pain conditions.

Background: Sleep problems (insomnia) and chronic pain are associated. Chronic pain and insomnia/insufficient sleep quality share similar symptoms and features. Although they have a bidirectional relationship, more research is needed to understand how they interact via mediators and how moderators influence this relationship. Aims: In this large clinical registry-based cohort study (N = 6,497), we investigate important mediators between insomnia and pain intensity in a cross-sectional sample of chronic pain patients using advanced path analysis. In addition, we investigate whether some background variables were moderators of the identified important paths or not and the correlation patterns between insomnia and pain intensity in relation to the mediators. Methods: This study includes a cohort of adult patients with chronic non-cancer pain from the Swedish Quality Registry for Pain Rehabilitation (SQRP) with data on patient-reported outcome measures (PROMs) (2008-2016). The PROMs cover the background, pain aspects, psychological distress, pain-related cognitions, activity/participation, and health-related quality of life variables of the patients. Partial least squares structural equation modeling was used to explore the direct and indirect (via mediators) relationships between insomnia and pain intensity at baseline. Results: In this cohort study, insomnia was prevalent at 62.3%, and both direct and indirect mediating paths were present for the insomnia-pain intensity relationship. All of the mediating effects combined were weaker than the direct effect between insomnia and pain intensity. The mediating effects via catastrophizing and acceptance showed the strongest and equal mediating paths, and mediating effects via fear avoidance were the second strongest. Insomnia showed stronger direct significant correlations with psychological distress, catastrophizing, and acceptance compared with those of pain intensity. Sex, age, education level, spatial extent of pain, or body mass index did not moderate the mediating paths. Discussion and conclusion: This study confirms the existence of significant direct and mediating paths between reported insomnia and pain intensity. Future studies should focus on illuminating how sleep interventions influence pain intensity and other important key factors that contribute to the distress of chronic pain patients.

Effects of interdisciplinary pain rehabilitation programs on neuropathic and non-neuropathic chronic pain conditions - a registry-based cohort study from Swedish Quality Registry for Pain Rehabilitation (SQRP).

BACKGROUND AND AIM: Neuropathic pain arises as a direct consequence of a lesion or disease affecting the somatosensory system. Pharmacological treatments for neuropathic pain often fail despite following guidelines. Interdisciplinary Pain Rehabilitation Programs (IPRP) are an effective intervention for chronic pain conditions. Little research has investigated whether IPRP can benefit patients with chronic neuropathic pain compared to other chronic pain conditions. This study assesses the real-world effects of IPRP on patients with chronic neuropathic pain compared to non-neuropathic patients using Patient-Reported Outcome Measures (PROMs) available in the Swedish Quality Registry for Pain Rehabilitation (SQRP). METHODS: A neuropathic group of patients (n = 1,654) were identified in two steps. This group was compared to a non-neuropathic group (n = 14,355) composed of common diagnoses (low back pain, fibromyalgia, whiplash associated disorders, and Ehlers-Danlos Syndrome) in relation to background variables, three overall outcome variables, and mandatory outcome variables (pain intensity, psychological distress symptoms, activity/participation aspects and health-related quality of life variables). Of these patients 43-44% participated in IPRP. RESULTS: At assessment, the neuropathic group reported significantly (with small effect sizes (ES)) more physician visits the previous year, older age, shorter pain durations, and less spatial extent of the pain (moderate ES). Moreover, for the 22 mandatory outcome variables, we found only clinically insignificant differences according to ESs between the groups. For patients participating in IPRP, the neuropathic group displayed equal or in some cases slightly superior results compared to the non-neuropathic group. DISCUSSION AND CONCLUSION: After assessing the real-world effects of IPRP, this large study found that neuropathic pain patients can benefit from the IPRP intervention. Both registry studies and RCTs are needed to better understand which patients with neuropathic pain are most suitable for IPRP and to what extent special considerations need to be made for these patients within the framework of IPRP.

Pain intensity and psychological distress show different associations with interference and lack of life control: A clinical registry-based cohort study of >40,000 chronic pain patients from SQRP.

Background: Both chronic pain and depressive and/or anxiety symptoms are associated with negative impacts on daily living, including interference and lack of life control. However, little is known about how pain and psychological distress affect these impacts. Aim: The first aim was to assess how pain intensity, psychological distress, and social support interact with interference and lack of life control. A second aim was to investigate whether the strength of these relationships is moderated by the presence or absence of depression and/or anxiety. Subjects and methods: Patient-Reported Outcome Measures (PROMs), which are available in the Swedish Quality Registry for Pain Rehabilitation (SQRP), were retrieved for patients with chronic pain (N = 40,184). A theoretical model with the constructs/latent variables pain intensity, psychological distress, interference, lack of life control, and social support was proposed and analyzed using Partial Least Squares Structural Equation Modelling (PLS-SEM). Indicators for these constructs were identified from the PROMs of the SQRP. Two models of the total cohort, which differed with respect to the causal relationship between pain intensity and psychological distress, were investigated. The moderating effects of anxiety and/or depression were also analyzed. Results: Relatively low correlation and explanatory power (R 2 = 0.16) were found for the pain intensity-psychological distress relationship. Pain intensity had a stronger effect on interference than on lack of life control. The reverse was found for psychological distress - i.e., psychological distress seemed to have a higher negative influence on function than on interference. The underlying assumption of the causal relationship between pain intensity and psychological distress determined how strong pain intensity and psychological distress influenced interference and lack of life control. Social support showed very similar absolute significant correlations with interference and lack of life control. Interference and lack of life control showed relatively weak associations. The psychological distress level was a moderating factor for several of the paths investigated. Discussion and conclusion: A clinical treatment consequence of the low correlation between pain intensity and psychological distress may be that clinically treating one may not reduce the effect of the other. The relative importance of pain intensity and psychological distress on interference and lack of life control depends on the underlying assumption concerning the pain intensity-psychological distress relationship. Interference and lack of life control showed relatively weak associations, underscoring the need to clinically assess them separately. Social support influenced both impact constructs investigated. The cohort display heterogeneity and thus presence of definite signs of anxiety and/or depression or not was a moderating factor for several of the associations (paths) investigated. The results are important both for the assessments and the design of treatments for patients with chronic pain.

Swedish Chronic Pain Biobank: protocol for a multicentre registry and biomarker project.

INTRODUCTION: About 20% of the adult population have chronic pain, often associated with psychological distress, sick leave and poor health. There are large variations in the clinical picture. A biopsychosocial approach is used in investigation and treatment. The concept of personalised medicine, that is, optimising medication types and dosages for individual patients based on biomarkers and other patient-related factors, has received increasing attention in different diseases but used less in chronic pain. This cooperative project from all Swedish University Hospitals will investigate whether there are changes in inflammation and metabolism patterns in saliva and blood in chronic pain patients and whether the changes correlate with clinical characteristics and rehabilitation outcomes. METHODS AND ANALYSIS: Patients at multidisciplinary pain centres at University Hospitals in Sweden who have chosen to participate in the Swedish Quality Registry for Pain Rehabilitation and healthy sex-matched and age-matched individuals will be included in the study. Saliva and blood samples will be collected in addition to questionnaire data obtained from the register. From the samples, proteins, lipids, metabolites and micro-RNA will be analysed in relation to, for example, diagnosis, pain characteristics, psychological distress, body weight, pharmacological treatment and clinical rehabilitation results using advanced multivariate data analysis and bioinformatics. ETHICS AND DISSEMINATION: The study is approved by the Swedish Ethical Review Authority (Dnr 2021-04929) and will be conducted in accordance with the declaration of Helsinki.The results will be published in open access scientific journals and in popular scientific relevant journals such as those from patient organisations. Data will be also presented in scientific meetings, meeting with healthcare organisations and disseminated in different lecturers at the clinics and universities.

Utilization of healthcare and prescription medicines after non-pharmacological interventions for depression - A 3-year register follow-up of an RCT in primary care.

Depression is a common, recurrent disorder. There is a need for readily available treatments with few negative side effects, that demands little resources and that are effective both in the short- and long term. Our aim was to investigate the long-term effectiveness of two different interventions; physical exercise and internet-based cognitive behavioural therapy (internet-CBT), compared to usual care in patients with mild to moderate depression in a Swedish primary care setting. We performed a register-based 3-year follow-up study of participants in the randomized controlled trial REGASSA (n = 940) using healthcare utilization and dispensed medicines as outcomes. We found no difference between the three groups regarding proportion of participants consulting healthcare due to mental illness or pain during follow-up. Regarding number of consultations, there was no difference between the groups, except for consultations related to pain. For this outcome both treatment arms had significantly fewer consultations compared to usual care, during year 2-3, the risk ratio (RR) for physical exercise and internet-CBT was 0.64 (95% CI = 0.43-0.95) and 0.61 (95% CI = 0.41-0.90), respectively. A significantly lower proportion of patients in both treatment arms were dispensed hypnotics and sedatives year 2-3 compared to the usual care arm, RR for both physical exercise and internet-CBT was 0.72 (95% CI = 0.53-0.98). No other differences between the groups were found. In conclusion, considering long-term effects, both physical exercise and internet-CBT, being resource-efficient treatments, could be considered as appropriate additions for patients with mild to moderate depression in primary care settings. Trial registration: The original RCT was registered with the German Clinical Trial Register (DRKS study ID: DRKS00008745).

Prevalence of Long-Term Opioid Therapy in a Chronic Non-Cancer Pain Population Attending a University-Based Tertiary Pain Clinic in Sweden: A Cross-Sectional Study.

BACKGROUND: Opioid therapy is a common treatment for chronic pain, despite accumulating evidence regarding harm and a lack of data to support the efficacy of long-term treatment. The prevalence of opioid therapy in Swedish patients with chronic non-cancer pain is unknown. The aim of this study was to assess a short-term period prevalence of prescribed opioid-use and long-term opioid therapy in a population with complex chronic non-cancer pain. METHODS: The study population comprised 1,613 patients with chronic non-cancer pain referred to a university-based tertiary pain clinic in Sweden during 2015-17. Data from a 360-day period prior to consultation were extracted from the Swedish Quality Registry for Pain Rehabilitation (SQRP) and Swedish Prescribed Drug Register (SPDR). Milligram morphine equivalents per day (MME/day) for dispensed opioids were analysed for a 90-day period preceding consultation, and long-term opioid therapy was determined for the entire 360-day period. RESULTS: The 90-day prevalence was 38% (95% confidence interval (95% CI) 36.0-40.8%) and 360-day prevalence was 22.3% (n=360, 95% CI 20.4-24.4%). CONCLUSION: Prescribing rates of opioids in a Swedish population with complex non-cancer chronic pain were high; 2 in 5 patients were dispensed an opioid within a 90-day period prior to consultation.

Outcomes of Interdisciplinary Pain Rehabilitation Across Subgroups of the Multidimensional Pain Inventory - A Study From the Swedish Quality Registry for Pain Rehabilitation.

INTRODUCTION: The Multidimensional Pain Inventory (MPI) is frequently used in the assessment of chronic pain. Three subgroups have been derived from MPI: adaptive coper (AC), dysfunctional (DYS), and interpersonally distressed (ID). The primary aim of this study was to examine whether outcome of Interdisciplinary Multimodal Pain Rehabilitation Programs (IMMRPs) differed across the MPI subgroups. METHODS: Patients with chronic pain (N = 34,513), included in the Swedish Quality Registry for Pain Rehabilitation, were classified into MPI subgroups and a subset that participated in IMMRPs (N = 13,419) was used to examine overall treatment outcomes using a previously established Multivariate Improvement Score (MIS) and 2 retrospective patient-evaluated benefits from treatment. RESULTS: The subgroups differed on sociodemographic characteristics, pain duration, and spatial spreading of pain. DYS and ID had the best overall outcomes to MIS. AC had the best outcomes according to the 2 retrospective items. Transition into other subgroups following IMMRP was common and most prominent in DYS and least prominent in AC. CONCLUSION: The validity of the MPI subgroups was partially confirmed. DYS and ID had the most severe clinical presentations at baseline and showed most improvement following IMMRP, but overall severity in DYS and ID at post-treatment was still higher than in the AC group. Future studies should examine how processes captured by MPI interact with neurobiological, medical, sociodemographic, and adaptation/coping factors and how these interactions impact severity of chronic pain and treatment outcome.

Spreading of Pain in Patients with Chronic Pain is Related to Pain Duration and Clinical Presentation and Weakly Associated with Outcomes of Interdisciplinary Pain Rehabilitation: A Cohort Study from the Swedish Quality Registry for Pain Rehabilitation (SQRP).

INTRODUCTION: The extent to which pain is distributed across the body (spreading of pain) differs largely among patients with chronic pain conditions and widespread pain has been linked to poor quality of life and work disability. A longer duration of pain is expected to be associated with more widespread pain, but studies are surprisingly scarce. Whether spreading of pain is associated with clinical presentation and treatment outcome in patients seen in interdisciplinary multimodal pain rehabilitation programs (IMMRPs) is unclear. The association between spreading of pain and (1) pain duration (2) clinical presentation (eg, pain intensity, pain-related cognitions, psychological distress, activity/participation aspects and quality of life) and (3) treatment outcome were examined. METHODS: Data from patients included in the Swedish Quality Registry for Pain Rehabilitation were used (n=39,916). A subset of patients that participated in IMMRPs (n=14,666) was used to examine whether spreading of pain at baseline predicted treatment outcome. Spreading of pain was registered using 36 predefined anatomical areas which were summarized and divided into four categories: 1-6 regions with pain (20.6% of patients), 7-12 regions (26.8%), 13-18 regions (22.0%) and 19-36 regions (30.6%). RESULTS: More widespread pain was associated with a longer pain duration and a more severe clinical picture at baseline with the strongest associations emerging in relation to health and pain aspects (pain intensity, pain interference and pain duration). Widespread pain was associated with a poorer overall treatment outcome following IMMRPs at both posttreatment and at a 12-month follow-up, but effect sizes were small. DISCUSSION: Spreading of pain is an indicator of the duration and severity of chronic pain and to a limited extent to outcomes of IMMRP. Longer pain duration in those with more widespread pain supports the concept of early intervention as clinically important and implies a need to develop and improve rehabilitation for patients with chronic widespread pain.

Influences of Sex, Education, and Country of Birth on Clinical Presentations and Overall Outcomes of Interdisciplinary Pain Rehabilitation in Chronic Pain Patients: A Cohort Study from the Swedish Quality Registry for Pain Rehabilitation (SQRP).

This study investigates the effects of sex, education, and country of birth on clinical presentations and outcomes of interdisciplinary multimodal pain rehabilitation programs (IMMRPs). A multivariate improvement score (MIS) and two retrospective estimations of changes in pain and ability to handle life situations were used as the three overall outcomes of IMMRPs. The study population consisted of chronic pain patients within specialist care in the Swedish Quality Registry for Pain Rehabilitation (SQRP) between 2008 and 2016 at baseline (n = 39,916), and for the subset participating in IMMRPs (n = 14,666). A cluster analysis based on sex, education, and country of origin revealed significant differences in the following aspects: best baseline clinical situation was for European women with university educations and the worst baseline clinical situation was for all patients born outside Europe of both sexes and different educations (i.e., moderate-large effect sizes). In addition, European women with university educations also had the most favorable overall outcomes in response to IMMRPs (small effect sizes). These results raise important questions concerning fairness and equality and need to be considered when optimizing assessments and content and delivery of IMMRPs for patients with chronic pain.

Moderate and Stable Pain Reductions as a Result of Interdisciplinary Pain Rehabilitation-A Cohort Study from the Swedish Quality Registry for Pain Rehabilitation (SQRP).

Few studies have investigated the real-life outcomes of interdisciplinary multimodal pain rehabilitation programs (IMMRP) for chronic pain. This study has four aims: investigate effect sizes (ES); analyse correlation patterns of outcome changes; define a multivariate outcome measure; and investigate whether the clinical self-reported presentation pre-IMMRP predicts the multivariate outcome. To this end, this study analysed chronic pain patients in specialist care included in the Swedish Quality Registry for Pain Rehabilitation for 22 outcomes (pain, psychological distress, participation, and health) on three occasions: pre-IMMRP, post-IMMRP, and 12-month follow-up. Moderate stable ES were demonstrated for pain intensity, interference in daily life, vitality, and health; most other outcomes showed small ES. Using a Multivariate Improvement Score (MIS), we identified three clusters. Cluster 1 had marked positive MIS and was associated with the overall worst situation pre-IMMRP. However, the pre-IMMRP situation could only predict 8% of the variation in MIS. Specialist care IMPRPs showed moderate ES for pain, interference, vitality, and health. Outcomes were best for patients with the worst clinical presentation pre-IMMRP. It was not possible to predict who would clinically benefit most from IMMRP.

Acute and long-term psychiatric side effects of mefloquine: a follow-up on Danish adverse event reports.

BACKGROUND: The aim of the study was to explore the profile of acute and long-term psychiatric side effects associated with mefloquine. METHODS: Subjects (n = 73) reported to a Danish national register during five consecutive years for mefloquine associated side effects were included. Acute psychiatric side effects were retrospectively assessed using the SCL-90-R and questions based on Present State Examination (PSE). Subjects reporting suspected psychotic states were contacted for a personal PSE interview. Electronic records of psychiatric hospitalizations and diagnoses were cross-checked. Long-term effects were evaluated with SF-36. SCL-90-R and SF-36 data were compared to age- and gender matched controls. RESULTS: In the SCL-90-R, clinically significant scores for anxiety, phobic anxiety and depression were found in 55%, 51%, and 44% of the mefloquine group. Substantial acute phase psychotic symptoms were found in 15% and were time-limited. Illusions/hallucinations were more frequently observed among women. Cases of hypomania/mania in the acute phase were 5.5%. Significant long-term mental health effects were demonstrated for the SF-36 subscales mental health (MH), role emotional (RE), and vitality (VT) in the mefloquine group compared to matched controls. CONCLUSION: The most frequent acute psychiatric problems were anxiety, depression, and psychotic symptoms. Data indicated that subjects experiencing acute mefloquine adverse side effects may develop long-term mental health problems with a decreased sense of global quality of life with lack of energy, nervousness, and depression.