| 1. |
- King, L. K., et al.
(författare)
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“You don't put it down to arthritis” : A qualitative study of the first symptoms recalled by individuals with knee osteoarthritis
- 2024
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Ingår i: Osteoarthritis and Cartilage Open. - 2665-9131. ; 6:1
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Tidskriftsartikel (refereegranskat)abstract
- Objective: As part of the first phase of the OARSI Early-stage Symptomatic Knee Osteoarthritis (EsSKOA) initiative, we explored the first symptoms and experiences recalled by individuals with knee osteoarthritis (OA). Design: This qualitative study, informed by qualitative description, was a secondary analysis of focus groups (n = 17 groups) and one-on-one interviews (n = 3) conducted in 91 individuals living with knee OA as part of an international study to better understand the OA pain experience. In each focus group or interview, participants were asked to describe their first symptoms of knee OA. We inductively coded these transcripts and conducted thematic analysis. Results: Mean age of participants was 70 years (range 47–92) and 68 % were female. We developed four overarching themes: Insidious and Episodic Onset, Diverse Early Symptoms, Must be Something Else, and Adjustments. Participants described the gradual and intermittent way in which symptoms of knee OA developed over many years; many could not identify a specific starting point. Participants described diverse initial knee symptoms, including activity-exacerbated joint pain, stiffness and crepitus. Most participants dismissed early symptoms or rationalized their presence, employing various strategies to enable continued participation in recreational and daily activities. Few sought medical attention until physical functioning was demonstrably impacted. Conclusions: The earliest symptoms of knee OA are frequently insidious in onset, episodic and present long before individuals present to health professionals. These results highlight challenges to identifying people with knee OA early and support the development of specific classification criteria for EsSKOA to capture individuals at an early stage.
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| 2. |
- Snoeker, B. A.M., et al.
(författare)
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Is meniscal status in the anterior cruciate ligament injured knee associated with change in bone surface area? An exploratory analysis of the KANON trial
- 2021
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Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 29:6, s. 841-848
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To study bone shape changes as a potential early feature of post-traumatic structural knee OA development, we estimated the association between meniscal status in the anterior cruciate ligament (ACL) injured knee and longitudinal condyle changes in bone surface area. Design: We used data from the KANON trial, including 121 young ACL-injured adults. We obtained baseline and 2-year follow-up knee MRIs. Our outcome was change in the bone surface areas (mean mm2, log-transformed) in 4 locations (femur, tibia, patella, and trochlea femur) in the medial and lateral compartment from baseline to 2 years. Meniscal pathology was defined as both present at baseline and newly developed (i.e., incident or progressed) using ACLOAS. We used multilevel linear regression adjusted for baseline bone area, age, sex, body mass index, treatment arm (i.e., early or optional delayed ACL reconstruction), and location. We analyzed medial and lateral compartment separately. We present results as percentage (%) bone area change difference with 95% confidence intervals (CI). Results: We analyzed 109 subjects (median 27 (18–36) years, 83% men) due to missing MRI information. The bone surface area increased on average by ∼2% over 2 years. The differences between knees with and without baseline meniscal pathology were 1.1% (95%CI 0.0–2.3%) and 1.4% (95%CI 0.6–2.2%) in the medial and lateral compartment, respectively, and 1.2% (95%CI 0.3–2.0%) and 1.3% (95%CI 0.6–2.0%) for medial and lateral newly developed pathology, respectively. Conclusion: Our finding of ∼1% increase bone area in compartment with meniscal pathology suggests a potentially important association between meniscal integrity and early bone surface area changes after ACL injury. Trial registration number ISRCTN 84752559.
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| 3. |
- A, Dell'Isola, et al.
(författare)
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The role of pain and walking difficulties in shaping willingness to undergo joint surgery for osteoarthritis: Data from the Swedish BOA register
- 2021
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Ingår i: Osteoarthritis and Cartilage Open. - : Elsevier BV. - 2665-9131. ; 3:2
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To investigate whether the association between pain intensity and willingness to undergo surgery is explained by walking difficulties, in patients with knee or hip osteoarthritis (OA). Methods: This is an observational study using data from the Better management of patients with Osteoarthritis (BOA) register, which collects data from a publicly financed self-management programme for people with OA in Sweden. We included all patients with knee or hip OA who attended the baseline visit between 2008 and 2016. We conducted separate mediation analyses within a counterfactual framework to estimate the mediation effect of walking difficulties (yes/no) on willingness to undergo surgery (yes/no) for each one-point increase in pain (0–10 on a numeric rating scale), adjusted for relevant confounders. Results: We included 72,131 patients (69% women, mean age 66, mean pain 5.4, 81% had walking difficulties, 27% was willing to undergo surgery). A one-point increase in pain intensity was associated with 1.53 (95% CI: 1.51; 1.55) higher odds of being willing to undergo surgery. Walking difficulties mediated 10%–25% of the effect of one-point increase in pain when pain was <8/10, while at pain ≥8/10 this percentage decreased to 3%. Conclusions: More than 80% of the BOA patients have mild to moderate pain (<8/10) and walking difficulties can mediate up to a quarter of the total effect of pain on the willingness to undergo surgery in these patients. Trials to evaluate the potential to lower surgery demand by reducing walking difficulties in people with these characteristics are needed.
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| 4. |
- Hellberg, I., et al.
(författare)
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3D analysis and grading of calcifications from ex vivo human meniscus
- 2023
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Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 31:4, s. 482-492
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Meniscal calcifications are associated with the pathogenesis of knee osteoarthritis (OA). We propose a micro-computed tomography (μCT) based 3D analysis of meniscal calcifications ex vivo, including a new grading system. Method: Human medial and lateral menisci were obtained from 10 patients having total knee replacement for medial compartment OA and 10 deceased donors without knee OA (healthy references). The samples were fixed; one subsection was imaged with μCT, and the adjacent tissue was processed for histological evaluation. Calcifications were examined from the reconstructed 3D μCT images, and a new grading system was developed. To validate the grading system, meniscal calcification volumes (CVM) were quantitatively analyzed and compared between the calcification grades. Furthermore, we estimated the relationship between histopathological degeneration and the calcification severity. Results: 3D μCT images depict calcifications in every sample, including diminutive calcifications that are not visible in histology. In the new grading system, starting from grade 2, each grade results in a CVM that is 20.3 times higher (95% CI 13.3–30.5) than in the previous grade. However, there was no apparent difference in CVM between grades 1 and 2. The calcification grades appear to increase with the increasing histopathological degeneration, although histopathological degeneration is also observed with small calcification grades. Conclusions: 3D μCT grading of meniscal calcifications is feasible. Interestingly, it seems that there are two patterns of degeneration in the menisci of our sample set: 1) with diminutive calcifications (calcification grades 1–2), and 2) with large to widespread calcifications (calcification grades 3–5).
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| 5. |
- Karjalainen, V. P., et al.
(författare)
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Quantitative three-dimensional collagen orientation analysis of human meniscus posterior horn in health and osteoarthritis using micro-computed tomography
- 2021
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Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 29:5, s. 762-772
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Knee osteoarthritis (OA) is associated with meniscal degeneration that may involve disorganization of the meniscal collagen fiber network. Our aims were to quantitatively analyze the microstructural organization of human meniscus samples in 3D using micro-computed tomography (μCT), and to compare the local microstructural organization between OA and donor samples. Method: We collected posterior horns of both medial and lateral human menisci from 10 end-stage medial compartment knee OA patients undergoing total knee replacement (medial & lateral OA) and 10 deceased donors without knee OA (medial & lateral donor). Posterior horns were dissected and fixed in formalin, dehydrated in ascending ethanol concentrations, treated with hexamethyldisilazane (HMDS), and imaged with μCT. We performed local orientation analysis of collagenous microstructure in 3D by calculating structure tensors from greyscale gradients within selected integration window to determine the polar angle for each voxel. Results: In donor samples, meniscus bundles were aligned circumferentially around the inner border of meniscus. In medial OA menisci, the organized structure of collagen network was lost, and main orientation was shifted away from the circumferential alignment. Quantitatively, medial OA menisci had the lowest mean orientation angle compared to all groups, −24° (95%CI -31 to −18) vs medial donor and −25° (95%CI -34 to −15) vs lateral OA. Conclusions: HMDS-based μCT imaging enabled quantitative analysis of meniscal collagen fiber bundles and their orientations in 3D. In human medial OA menisci, the collagen disorganization was profound with overall lower orientation angles, suggesting collagenous microstructure disorganization as an important part of meniscus degradation.
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| 6. |
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| 7. |
- Snoeker, B. A.M., et al.
(författare)
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Are structural abnormalities on knee MRI associated with osteophyte development? Data from the Osteoarthritis Initiative
- 2021
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Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 29:12, s. 1701-1708
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To assess which structural abnormalities on knee MRI are associated with development of osteophytes in middle-aged subjects without radiographic knee osteoarthritis. Design: We included subjects from the Osteoarthritis Initiative, aged 40–55 years, Kellgren & Lawrence grade 0 in both knees, and knee MRIs from both knees available at baseline, 24, 48 and 72 months. Structural exposures on MRI assessed using MOAKS included cartilage damage, bone marrow lesions, meniscal tear, meniscal extrusion, and Hoffa/effusion synovitis. We assessed whether each structural exposure was associated with the development of osteophytes on MRI in the medial and lateral tibiofemoral, and patellofemoral compartment. We estimated hazard ratios (HR) including 95% confidence intervals (CI) for osteophyte development using a mixed complementary log–log regression model adjusted for age, sex, and body mass index. Results: We included 680 knees from 340 subjects with a mean (SD) age of 50 years (3.0), and 51% men. In the medial tibiofemoral compartment, the absolute risk of osteophyte development in the first 24-month period was 4% in knees without, and 15% in knees with medial meniscal tear. Corresponding adjusted HR was 6.6 (95%CI = 3.4–12.9). In the lateral tibiofemoral compartment, the adjusted HR for developing osteophytes having a lateral meniscal tear was 3.3 (95%CI = 1.3–8.4). In the patellofemoral compartment, patellofemoral cartilage damage was most clearly associated with developing osteophytes (HR = 2.6, 95%CI = 1.8–3.7). Conclusions: Meniscal tear seem to be the strongest structural risk factor for the development of tibiofemoral osteophytes, and patellofemoral cartilage damage for the development of patellofemoral osteophytes, respectively. Local biomechanical factors are important in early osteophyte development.
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| 8. |
- Struglics, A., et al.
(författare)
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Molecular and imaging biomarkers of local inflammation at 2 years after anterior cruciate ligament injury do not associate with patient reported outcomes at 5 years
- 2020
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Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 28:3, s. 356-362
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To estimate the association between molecular or imaging inflammatory biomarkers at 2 years after anterior cruciate ligament (ACL) injury and patient-reported outcomes at 5 years. Methods: For 116 ACL-injured patients, molecular biomarkers of inflammation (synovial fluid and serum cytokines) and Hoffa- and effusion-synovitis as visualized on magnetic resonance imaging (MRI) were assessed 2 years post-injury. Knee injury and Osteoarthritis Outcome Score (KOOS) and SF-36 were assessed at 2 and 5 years. We used multiple imputation to handle biomarker values that were below the level of detection or missing, and linear regression for statistical analyses. Results: None of the synovial fluid cytokines or imaging biomarkers of inflammation at 2 years were associated with any of the patient-reported outcomes at 5 years. With each log10 unit higher of serum tumor necrosis factor concentration the knee-related quality of life of KOOS was increased (i.e., better outcome) by 35 (95% confidence interval 7 to 63) points. No other serum biomarker measured at 2 years was associated with patient-reported outcome at 5 years. Conclusion: Local joint inflammation assessed by biomarkers in synovial fluid and Hoffa- and effusion-synovitis on MRI at 2 years after an ACL injury did not associate with patient-reported outcomes at 5 years. Thus, chronic inflammation in the ACL-injured knee, as reflected by the biomarkers studied here, seems not to be a key determinant for the long-term patient-reported outcomes.
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| 9. |
- Yu, D., et al.
(författare)
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Opioid use prior to total knee replacement : comparative analysis of trends in England and Sweden
- 2022
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Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 30:6, s. 815-822
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To describe and compare trends in the frequency of opioid prescribing/dispensing in English and Swedish patients with osteoarthritis prior to total knee replacement (TKR). Methods: 49,043 patients from an English national database (Clinical Practice Research Datalink) and 5,955 patients from the Swedish Skåne Healthcare register undergoing TKR between 2015 and 2019 were included, alongside 1:1 age-, sex-, and practice (residential area) matched controls. Annual prevalence and prevalence rates ratio (PRR) of opioid prescribing/dispensing (any, by strength) in the 10 years prior to TKR (or matched index date for controls) were estimated using Poisson regression. Results: In England and Sweden, the prevalence of patients with osteoarthritis receiving any opioid prior to TKR increased towards the date of surgery from 24% to 44% in England and from 16% to 33% in Sweden. Prescribing in controls was stable, resulting in an increasing PRR (1.6–2.7) between 10 and 1 years prior to index date in both countries. No relevant cohort or period effect was observed in either country. Prevalence of opioid prescribing was higher in English cases and controls; weaker opioids were more commonly prescribed in England, stronger opioids in Sweden. Conclusions: Temporal prevalence patterns of opioid prescribing between cases and controls are similar in England and Sweden. Opioids are still commonly used in TKR cases in both countries highlighting the lack of valid alternatives for OA pain management.
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| 10. |
- Ebrahimi, Mohammadhossein, et al.
(författare)
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Associations of human femoral condyle cartilage structure and composition with viscoelastic and constituent-specific material properties at different stages of osteoarthritis
- 2022
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Ingår i: Journal of Biomechanics. - : Elsevier BV. - 0021-9290. ; 145
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Tidskriftsartikel (refereegranskat)abstract
- The relationships between structure and function in human knee femoral cartilage are not well-known at different stages of osteoarthritis. Thus, our aim was to characterize the depth-dependent composition and structure (proteoglycan content, collagen network organization and collagen content) of normal and osteoarthritic human femoral condyle cartilage (n = 47) and relate them to their viscoelastic and constituent-specific mechanical properties that are obtained through dynamic sinusoidal testing and fibril-reinforced poroelastic material modeling of stress-relaxation testing, respectively. We characterized the proteoglycan content using digital densitometry, collagen network organization (orientation angle and anisotropy) using polarized light microscopy and collagen content using Fourier transform infrared spectroscopy. In the superficial cartilage (0–10 % of thickness), the collagen network disorganization and proteoglycan loss were associated with the smaller initial fibril network modulus - a parameter representing the pretension of the collagen network. Furthermore, the proteoglycan loss was associated with the greater strain-dependent fibril network modulus - a measure of nonlinear mechanical behavior. The proteoglycan loss was also associated with greater cartilage viscosity at a low loading frequency (0.005 Hz), while the collagen network disorganization was associated with greater cartilage viscosity at a high loading frequency (1 Hz). Our results suggest that proteoglycan loss and collagen network disorganization reduce the pretension of the collagen network while proteoglycan degradation also increases the nonlinear mechanical behavior of the collagen network. Further, the results also highlight that proteoglycan loss and collagen disorganization increase the viscosity of femoral cartilage, but their contribution to increased viscosity occurs in completely different loading frequencies.
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