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1.
  • Shraim, M. A., et al. (författare)
  • Features and methods to discriminate between mechanism-based categories of pain experienced in the musculoskeletal system: a Delphi expert consensus study
  • 2022
  • Ingår i: Pain. - : Ovid Technologies (Wolters Kluwer Health). - 0304-3959 .- 1872-6623. ; 163:9, s. 1812-1828
  • Tidskriftsartikel (refereegranskat)abstract
    • Classification of musculoskeletal pain based on underlying pain mechanisms (nociceptive, neuropathic, and nociplastic pain) is challenging. In the absence of a gold standard, verification of features that could aid in discrimination between these mechanisms in clinical practice and research depends on expert consensus. This Delphi expert consensus study aimed to: (1) identify features and assessment findings that are unique to a pain mechanism category or shared between no more than 2 categories and (2) develop a ranked list of candidate features that could potentially discriminate between pain mechanisms. A group of international experts were recruited based on their expertise in the field of pain. The Delphi process involved 2 rounds: round 1 assessed expert opinion on features that are unique to a pain mechanism category or shared between 2 (based on a 40% agreement threshold); and round 2 reviewed features that failed to reach consensus, evaluated additional features, and considered wording changes. Forty-nine international experts representing a wide range of disciplines participated. Consensus was reached for 196 of 292 features presented to the panel (clinical examination-134 features, quantitative sensory testing-34, imaging and diagnostic testing-14, and pain-type questionnaires-14). From the 196 features, consensus was reached for 76 features as unique to nociceptive (17), neuropathic (37), or nociplastic (22) pain mechanisms and 120 features as shared between pairs of pain mechanism categories (78 for neuropathic and nociplastic pain). This consensus study generated a list of potential candidate features that are likely to aid in discrimination between types of musculoskeletal pain.
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  • Carville, S F, et al. (författare)
  • EULAR evidence-based recommendations for the management of fibromyalgia syndrome
  • 2008
  • Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 67:4, s. 536-541
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To develop evidence-based recommendations for the management of fibromyalgia syndrome. Methods: A multidisciplinary task force was formed representing 11 European countries. The design of the study, including search strategy, participants, interventions, outcome measures, data collection and analytical method, was defined at the outset. A systematic review was undertaken with the keywords "fibromyalgia", "treatment or management" and "trial". Studies were excluded if they did not utilise the American College of Rheumatology classification criteria, were not clinical trials, or included patients with chronic fatigue syndrome or myalgic encephalomyelitis. Primary outcome measures were change in pain assessed by visual analogue scale and fibromyalgia impact questionnaire. The quality of the studies was categorised based on randomisation, blinding and allocation concealment. Only the highest quality studies were used to base recommendations on. When there was insufficient evidence from the literature, a Delphi process was used to provide basis for recommendation. Results: 146 studies were eligible for the review. 39 pharmacological intervention studies and 59 non-pharmacological were included in the final recommendation summary tables once those of a lower quality or with insufficient data were separated. The categories of treatment identified were antidepressants, analgesics, and "other pharmacological" and exercise, cognitive behavioural therapy, education, dietary interventions and "other non-pharmacological". In many studies sample size was small and the quality of the study was insufficient for strong recommendations to be made. Conclusions: Nine recommendations for the management of fibromyalgia syndrome were developed using a systematic review and expert consensus.
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  • Fernandez-de-las-Penas, C., et al. (författare)
  • Phenotyping Post-COVID Pain as a Nociceptive, Neuropathic, or Nociplastic Pain Condition
  • 2022
  • Ingår i: Biomedicines. - : MDPI AG. - 2227-9059. ; 10:10
  • Tidskriftsartikel (refereegranskat)abstract
    • Pain after an acute Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19) condition (post-COVID pain) is becoming a new healthcare emergency. Precision medicine refers to an evidence-based method of grouping patients based on their diagnostic/symptom presentation and then tailoring specific treatments accordingly. Evidence suggests that post-COVID pain can be categorized as nociceptive (i.e., pain attributable to the activation of the peripheral receptive terminals of primary afferent neurons in response to noxious chemical, mechanical, or thermal stimuli), neuropathic (i.e., pain associated with a lesion or disease of the somatosensory nervous system and limited to a "neuroanatomically plausible" distribution of the system), nociplastic (i.e., pain arising from altered nociception despite no clear evidence of actual or threatened tissue damage causing the activation of peripheral nociceptors or evidence for disease or lesion of the somatosensory system causing the pain), or mixed type (when two pain phenotypes co-exist). Each of these pain phenotypes may require a different treatment approach to maximize treatment effectiveness. Accordingly, the ability to classify post-COVID pain patients into one of these phenotypes would likely be critical for producing successful treatment outcomes. The 2021 International Association for the Study of Pain (IASP) clinical criteria and grading system provide a framework for classifying pain within a precision pain medicine approach. Here we present data supporting the possibility of grouping patients with post-COVID pain into pain phenotypes, using the 2021 IASP classification criteria, with a specific focus on nociplastic pain, which is probably the primary mechanism involved in post-COVID pain. Nociplastic pain, which is usually associated with comorbid symptomology (e.g., poor sleep quality, fatigue, cognitive-emotional disturbances, etc.) and is considered to be more difficult to treat than other pain types, may require a more nuanced multimodal treatment approach to achieve better treatment outcomes.
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  • Graven-Nielsen, T., et al. (författare)
  • Central hyperexcitability in fibromyalgia
  • 1999
  • Ingår i: Journal of Musculoskeletal Pain. - 1058-2452 .- 1540-7012. ; 7, s. 261-267
  • Tidskriftsartikel (refereegranskat)
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  • Fernandez-de-las-Penas, C., et al. (författare)
  • Carpal Tunnel Syndrome: Neuropathic Pain Associated or Not with a Nociplastic Condition
  • 2023
  • Ingår i: Biomedicines. - 2227-9059. ; 11:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Carpal tunnel syndrome (CTS) has been traditionally classified as primarily a neuropathic condition with or without pain. Precision medicine refers to an evidence-based method of grouping patients based on their susceptibility to biology, prognosis of a particular disease, or in their response to a specific treatment, and tailoring specific treatments accordingly. In 2021, the International Association for the Study of Pain (IASP) proposed a grading system for classifying patients into nociceptive, neuropathic, or nociplastic phenotypes. This position paper presents data supporting the possibility of subgrouping individuals with specific CTS related-pain into nociceptive, neuropathic, nociplastic or mixed-type phenotypes. Carpal tunnel syndrome is a neuropathic condition but can also be comorbid with a nociplastic pain condition. The presence of extra-median symptoms and the development of facilitated pain processing seem to be signs suggesting that specific CTS cases can be classified as the nociplastic pain phenotype. The clinical responses of therapeutic approaches for the management of CTS are inconclusive. Accordingly, the ability to identify the predominant pain phenotype in patients with CTS could likely be problematic for producing efficient treatment outcomes. In fact, the presence of a nociplastic or mixed-type pain phenotype would explain the lack of clinical effect of treatment interventions targeting the carpal tunnel area selectively. We propose a clinical decision tree by using the 2021 IASP classification criteria for identifying the predominant pain phenotype in people with CTS-related pain, albeit CTS being a priori a neuropathic pain condition. The identification of a nociplastic-associated condition requires a more nuanced multimodal treatment approach to achieve better treatment outcomes.
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  • Fernandez-de-las-Penas, C., et al. (författare)
  • Myofascial Pain Syndrome: A Nociceptive Condition Comorbid with Neuropathic or Nociplastic Pain
  • 2023
  • Ingår i: Life. - : MDPI AG. - 2075-1729. ; 13:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Myofascial pain syndrome is featured by the presence of myofascial trigger points (TrPs). Whether TrPs are primary or secondary phenomena or if they relate to central or peripheral nervous system disorders is controversial. Referred pain, a cardinal sign of TrPs, is a central phenomenon driven by peripheral input. In 2021, the International Association for the Study of Pain (IASP) proposed a clinical criteria and grading system for classifying patients with pain on nociceptive, neuropathic, or nociplastic phenotypes. Myofascial TrP pain has been traditionally categorized as a nociceptive phenotype; however, increasing evidence supports that this condition could be present in patients with predominantly nociplastic pain, particularly when it is associated with an underlying medical condition. The clinical response of some therapeutic approaches for managing TrPs remains unclear. Accordingly, the ability to classify myofascial TrP pain into one of these phenotypes would likely be critical for producing more successful clinical treatment outcomes by a precision medicine approach. This consensus paper presents evidence supporting the possibility of subgrouping individuals with myofascial TrP pain into nociceptive, nociplastic, or mixed-type phenotype. It is concluded that myofascial pain caused by TrPs is primarily a nociceptive pain condition, is unlikely to be classified as neuropathic or nociplastic, but can be present in patients with predominantly neuropathic or nociplastic pain. In the latter cases, management of the predominant central pain problem should be a major treatment goal, but the peripheral drive from TrPs should not be ignored, since TrP treatment has been shown to reduce sensitization-associated symptomatology in nociplastic pain conditions, e.g., fibromyalgia.
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  • Fernandez-de-las-Penas, C., et al. (författare)
  • Sensitization-Associated Post-COVID-19 Symptoms at 6 Months Are Not Associated with Serological Biomarkers at Hospital Admission in COVID-19 Survivors: A Secondary Analysis of a Cohort Study
  • 2022
  • Ingår i: Journal of Clinical Medicine. - : MDPI AG. - 2077-0383. ; 11:12
  • Tidskriftsartikel (refereegranskat)abstract
    • Individuals who survived coronavirus disease, 2019 (COVID-19), often have symptoms of sensitization, but the extent to which these symptoms relate to serological biomarkers remains unclear. Therefore, this secondary analysis evaluated the association between serological biomarkers at hospital admission with sensitization-associated post-COVID-19 symptoms in a sample of previously hospitalized COVID-19 survivors. Sixty-seven individuals hospitalized due to SARS-CoV-2 infection in one urban hospital of Madrid (Spain) during the first wave of the pandemic were assessed a mean of 6.0 (SD 0.8) months after hospital discharge. The Central Sensitization Inventory (CSI) was used as rough tool to estimate the presence of sensitization-associated post-COVID-19 symptoms (>= 40/100 points). Levels of 16 serological biomarkers collected at hospital admission were obtained from medical records. Twenty-four (35.8%) patients reported sensitization-associated post-COVID-19 symptoms (CSI >= 40 points). Subjects reporting sensitization-associated symptoms had lower ferritin and hemoglobin levels than those not reporting sensitization-associated post-COVID-19 symptoms; however, these differences were small. We observed significant but small negative associations of the CSI score with ferritin (r: -0.251, p = 0.04) and hemoglobin (r: -0.292, p = 0.017) levels. No other significant difference was found. In conclusion, this secondary analysis did not find significant associations between the investigated serological biomarkers at hospital admission and sensitization-associated post-COVID-19 symptoms at 6 months after hospitalization in COVID-19 survivors.
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  • Fernandez-de-las-Penas, C., et al. (författare)
  • Sensitization symptoms are associated with psychological and cognitive variables in COVID-19 survivors exhibiting post-COVID pain
  • 2023
  • Ingår i: Pain Practice. - : Wiley. - 1530-7085 .- 1533-2500. ; 23:1, s. 23-31
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective To investigate the association between demographic, clinical, psychological, cognitive, and health-related variables and the Central Sensitization Inventory (CSI) in previously hospitalized COVID-19 survivors exhibiting "de novo" post-COVID pain. Methods Seventy-seven (n = 77) COVID-19 survivors with "de novo" post-COVID pain completed demographic (age, height, and weight), clinical (duration and intensity of the pain), psychological (depressive/anxiety levels and sleep quality), cognitive (catastrophizing and kinesiophobia levels), and health-related quality of life variables as well as the CSI. A multivariable correlation analysis was conducted to determine the association between variables, and a stepwise multiple linear regression model was performed to identify CSI predictors. Results Patients were assessed a mean of 6.0 (SD 0.8) months after hospital discharge. Twenty-six (33.7%) individuals showed indications of sensitization-associated symptoms (CSI score >= 40 points). The CSI score was positively associated with pain intensity (r: 0.371), anxiety (r: 0.784), depressive (r: 0.709), catastrophizing (r: 0.620), and kinesiophobia (r: 0.359) levels (all, p < 0.001). The stepwise regression analysis revealed that 60.2% of CSI was explained by anxiety levels and pain intensity. Conclusion This study found that psychological and cognitive variables were associated with the CSI score in previously hospitalized COVID-19 survivors with "de novo" post-COVID pain. Anxiety levels and the intensity of pain symptoms were independently associated with CSI score suggesting a significant overlap with psychological construct. The "de novo" post-COVID pain association with CSI may indicate changes in the pain processing important for managing the pain.
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  • Graven-Nilsen, T, et al. (författare)
  • Ketamine reduces muscle pain, temporal summation, and referred pain in fibromyalgia patients
  • 2000
  • Ingår i: Pain. - 0304-3959 .- 1872-6623. ; 85:3, s. 483-491
  • Tidskriftsartikel (refereegranskat)abstract
    • Central mechanisms related to referred muscle pain and temporal summation of muscular nociceptive activity are facilitated in fibromyalgia syndrome (FMS) patients. The present study assessed the effects of an NMDA-antagonist (ketamine) on these central mechanisms. FMS patients received either i.v. placebo or ketamine (0.3 mg/kg, Ketalar(«)) given over 30 min on two separate occasions. Habitual pain intensity was assessed on a visual analogue scale (VAS). Initially, 29 FMS patients received ketamine or isotonic saline to determine which patients were ketamine responders (>50% decrease in pain intensity at rest by active drug on two consecutive VAS assessments). Fifteen out of 17 ketamine-responders were included in the second part of the study. Before and after ketamine or placebo, experimental local and referred pain was induced by intramuscular (i.m.) infusion of hypertonic saline (0.7 ml, 5%) into the tibialis anterior (TA) muscle. The saline-induced pain intensity was assessed on an electronic VAS, and the distribution of pain drawn by the subject. In addition, the pain threshold (PT) to i.m. electrical stimulation was determined for single stimulus and five repeated (2 Hz, temporal summation) stimuli. The pressure PT of the TA muscle was determined, and the pressure PT and pressure pain tolerance threshold were determined at three bilaterally located tenderpoints (knee, epicondyle, and mid upper trapezius). VAS scores of pain at rest were progressively reduced during ketamine infusion compared with placebo infusion. Pain intensity (area under the VAS curve) to the post-drug infusion of hypertonic saline was reduced by ketamine (-18.4▒0.3% of pre-drug VAS area) compared with placebo (29.9▒18.8%, P<0.02). Local and referred pain areas were reduced by ketamine (-12.0▒14.6% of pre-drug pain areas) compared with placebo (126.3▒83.2%, P<0.03). Ketamine had no significant effect on the PT to single i.m. electrical stimulation. However, the span between the PT to single and repeated i.m. stimuli was significantly decreased by the ketamine (-42.3▒15.0% of pre-drug PT) compared with placebo (50.5▒49.2%, P<0.03) indicating a predominant effect on temporal summation. Mean pressure pain tolerance from the three paired tenderpoints was increased by ketamine (16.6▒6.2% of pre-drug thresholds) compared with placebo (-2.3▒4.9%, P<0.009). The pressure PT at the TA muscle was increased after ketamine (42.4▒9.2% of pre-drug PT) compared with placebo (7.0▒6.6%, P<0.011). The present study showed that mechanisms involved in referred pain, temporal summation, muscular hyperalgesia, and muscle pain at rest were attenuated by the NMDA-antagonist in FMS patients. It suggested a link between central hyperexcitability and the mechanisms for facilitated referred pain and temporal summation in a sub-group of the fibromyalgia syndrome patients. Whether this is specific for FMS patients or a general phenomena in painful musculoskeletal disorders is not known. Copyright (C) 2000 International Association for the Study of Pain. Published by Elsevier Science B.V.
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19.
  • Holm, P. M., et al. (författare)
  • Strength training in addition to neuromuscular exercise and education in individuals with knee osteoarthritis—the effects on pain and sensitization
  • 2021
  • Ingår i: European Journal of Pain (United Kingdom). - : Wiley. - 1090-3801 .- 1532-2149. ; 25:9, s. 1898-1911
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: There is a lack of evidence of the relative effects of different exercise modes on pain sensitization and pain intensity in individuals with knee osteoarthritis (KOA). Methods: Ninety individuals with radiographic and symptomatic KOA, ineligible for knee replacement surgery, were randomized to 12weeks of twice-weekly strength training in addition to neuromuscular exercise and education (ST+NEMEX-EDU) or neuromuscular exercise and education alone (NEMEX-EDU). Outcomes were bilateral, lower-leg, cuff pressure pain- and tolerance thresholds (PPT, PTT), temporal summation (TS), conditioned pain modulation (CPM), self-reported knee pain intensity and number of painful body sites. Results: After 12weeks of exercise, we found significant differences in increases in PPT (−5.01kPa (−8.29 to −1.73, p=.0028)) and PTT (−8.02kPa (−12.22 to −3.82, p=.0002)) in the KOA leg in favour of ST+NEMEX-EDU. We found no difference in effects between groups on TS, CPM or number of painful body sites. In contrast, there were significantly greater pain-relieving effects on VAS mean knee pain during the last week (−8.4mm (−16.2 to −0.5, p=.0364) and during function (−16.0mm (−24.8 to −7.3, p=.0004)) in favour of NEMEX-EDU after 12weeks of exercise. Conclusion: Additional strength training reduced pain sensitization compared to neuromuscular exercise and education alone, but also attenuated the reduction in pain intensity compared to neuromuscular exercise and education alone. The study provides the first dose- and type-specific insight into the effects of a sustained exercise period on pain sensitization in KOA. Future studies are needed to elucidate the role of different exercise modes. Significance: This study is an important step towards better understanding the effects of exercise in pain management of chronic musculoskeletal conditions. We found that strength training in addition to neuromuscular exercise and education compared with neuromuscular exercise and education only had a differential impact on pain sensitization and pain intensity, but also that regardless of the exercise mode, the positive effects on pain sensitization and pain intensity were comparable to the effects of other therapeutic interventions for individuals with knee osteoarthritis. © 2021 European Pain Federation - EFIC®
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  • Jackson, A., et al. (författare)
  • Patients with symptomatic permanent atrial fibrillation show quantitative signs of pain sensitisation
  • 2021
  • Ingår i: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 42:Suppl. 1, s. 416-416
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Background/Introduction: Most patients with atrial fibrillation (AF) report symptoms, while around one-third are asymptomatic. We hypothesized that sensory processing, in particular pain, differs in patients with symptomatic and asymptomatic AF.Purpose: To assess differences in pain sensitisation in patients with symptomatic and asymptomatic AF.Methods: Thirty individuals with permanent AF (15 symptomatic, 15 asymptomatic) completed the AF6 and SF-36 questionnaires and underwent quantitative pain sensitisation testing using pressure algometry at the sternum (referred pain area) and the tibialis anterior muscle (generalized pain area). The primary objective was to assess differences in pressure pain thresholds (PPT), temporal summation of pain (TSP), and conditioned pain modulation (CPM) in the two groups. The secondary objective was to determine association of demographic and clinical parameters to quantitative measures of pain sensitisation.Results: The symptomatic group had lower PPTs at both tibialis (p=0.004) and sternum (p=0.01), as well as impaired CPM (p=0.025) and facilitated TSP (p=0.008) at the tibialis but not sternum, compared to the asymptomatic group. The AF6 sum score was negatively correlated to PPT on both tibialis (r=−0.50, p=0.005) and sternum (r=−0.42, p=0.02) and positively correlated to TSP of both tibialis (r=0.57, p=0.001) and sternum (r=0.45, p=0.01), but not to CPM. The physical component summary score was positively correlated to the PPT on both tibialis (r=0.52, p=0.003) and sternum (r=0.40, p=0.03) and negatively to TSP on the tibialis (r=−0.53, p=0.003) but not sternum.Conclusions: Patients with symptomatic AF exhibit lower pain tolerance than patients with asymptomatic AF, as well as impaired pain inhibitory control and facilitated summation of pain, indicating that pain sensitisation may be of importance in symptomatic AF.
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  • Liew, B. X. W., et al. (författare)
  • Distress and Sensitization as Main Mediators of Severity in Women with Fibromyalgia: A Structural Equation Model
  • 2022
  • Ingår i: Biomedicines. - : MDPI AG. - 2227-9059. ; 10:5
  • Tidskriftsartikel (refereegranskat)abstract
    • We aimed to explore a path model identified using a structural equation model (SEM) which best explains the multivariate contributions of sensitization, sensitivity, and emotional variables to clinical severity in women with FMS. Pain features, the Central Sensitization Inventory (CSI), painDETECT, S-LANSS, the Hospital Anxiety and Depression Scale (HADS), the Pittsburgh Sleep Quality Index (PSQI), the Pain Catastrophizing Scale (PCS), the Pain Vigilance and Awareness Questionnaire (PVAQ), the 11-item Tampa Scale for Kinesiophobia (TSK-11), and pressure pain thresholds (PPTs) were collected from 113 women with FMS. Four latent variables were created: severity (clinical pain features), sensitivity (PPTs), sensitization (S-LANSS, CSI, painDETECT), and distress (HADS-A, HADS-D, PCS, PVAQ, TSK-11). Data fit for the measurement model were considered excellent (RMSEA = 0.043, CFI = 0.966, SRMR = 0.067, and NNFI = 0.960). Distress had a significant relationship with the mediators of sleep (beta = 0.452, p = 0.031) and sensitization (beta = 0.618, p = 0.001). The only mediator with a significant effect (beta = 1.113, p < 0.001) on severity was sensitization. A significant indirect effect of sensitization (beta = 0.687, p = 0.001) that explained the relationship between distress and severity was also identified. The proposed model suggests that distress and sensitization, together with poor sleep, have a complex mediating effect on severity in women with FMS. The identified path model can be leveraged in clinical trials investigating treatment approaches for FMS.
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  • Schepman, P., et al. (författare)
  • Factors influencing quality of life in patients with osteoarthritis: analyses from the BISCUITS study
  • 2022
  • Ingår i: Scandinavian Journal of Pain. - : Walter de Gruyter GmbH. - 1877-8860 .- 1877-8879. ; 23:1, s. 139-148
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: Osteoarthritis can have a profound effect on patients' quality of life. The Burden of Disease and Management of Osteoarthritis and Chronic Low Back Pain: Health Care Utilization and Sick Leave in Sweden, Norway, Finland and Denmark (BISCUITS) study aimed to describe the impact of osteoarthritis on quality of life and determine the association with factors such as pain severity and pharmacological treatment. Methods: An observational study was performed with a cross-sectional design including patients with a confirmed osteoarthritis diagnosis enrolled in the National Quality Register for Better management of patients with Osteoarthritis (BOA) between 2016 and 2017 in Sweden. Patient-reported information from BOA was linked to administrative data from three national health registers. The impact of osteoarthritis on quality of life was estimated using the EQ-5D-5L and the first developed experienced-based time-trade-off value set for Sweden to calculate the EQ-5D-5L index scores. EQ-5D-3L index scores were also estimated based on a UK hypothetical value set via a crosswalk method. Ordinary least squares regression models were used to analyse the association between quality of life and potential influencing factors. Results: For the 34,254 patients evaluated, mean EQ-5D-5L index score was 0.792 (SD 0.126). Stratifications showed that the index score varied across different levels of pain severity. Increased pain severity and use of pain-relieving medications remained significantly associated with a lower quality of life index score when controlled for potential confounders. The mean EQ-5D-3L index score was 0.605 (SD 0.192). Conclusions: This large population-based study from Sweden highlights the substantial impact of osteoarthritis on quality of life amongst different patient groups and that currently available treatment options for osteoarthritis pain do not appropriately address the needs for many osteoarthritis patients.
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