Publications

@article{kiadaliri_uncovering_2025,
	title = {Uncovering sociodemographic disparities in temporal trends of osteoarthritis incidence and age-at-diagnosis, 2006-2019},
	volume = {53},
	issn = {1651-1905},
	doi = {10.1177/14034948241265427},
	abstract = {AIM: To describe sociodemographic disparities in temporal trends of incidence and age distributions of first registered osteoarthritis (OA) diagnosis in southern Sweden.
METHODS: We identified all Skåne residents aged 35+ who had lived in the region at any point during the period 2006-2019 with no previous OA diagnosis (ICD-10 codes M15-M19) for 8 years prior to inclusion in the study (n = 849,061). We calculated person-years from inclusion until OA diagnosis, death, emigration, or 31 December 2019, whichever occurred first. Combining sex (female, male), education (low, medium, high) and nativity (Swedish, immigrant), we created a variable with 12 strata. Average annual percent changes in age-standardized incidence rates were estimated using joinpoint regression. Changes in the median age-at-diagnosis (year of diagnosis minus birth year), weighted to the mid-2005 Swedish population, were explored.
RESULTS: Cumulative age-standardized incidence rates ranged from 116 (95\% CI: 111, 121) per 10,000 person-years for immigrant males with low education to 205 (95\% CI: 200, 210) for immigrant females with medium education. The estimated average annual percent changes (ranging from 3.4\% to 6.1\%) were generally similar, with slightly greater variations among immigrants than Swedes. The weighted median age-at-diagnosis was higher for Swedes and low educated people. Immigrant females with low education were the only stratum with a reduction (3 years) in the weighted median age-at-diagnosis over time. Sociodemographic patterns in knee OA incidence were different from patterns for hip OA.
CONCLUSIONS: There were few sociodemographic disparities in temporal trends of OA incidence and age-at-diagnosis, suggesting persistent sociodemographic disparities in OA burden in southern Sweden.},
	language = {eng},
	number = {7},
	journal = {Scandinavian Journal of Public Health},
	author = {Kiadaliri, Ali and Englund, Martin},
	month = nov,
	year = {2025},
	keywords = {Adult, Age Distribution, Age at diagnosis, Age of Onset, Aged, Aged, 80 and over, Emigrants and Immigrants, Female, Health Status Disparities, Humans, Incidence, Male, Middle Aged, Osteoarthritis, Sociodemographic Factors, Socioeconomic Factors, Sweden, intersectional inequality, osteoarthritis, temporal trend},
	pages = {747--755},
}

AIM: To describe sociodemographic disparities in temporal trends of incidence and age distributions of first registered osteoarthritis (OA) diagnosis in southern Sweden. METHODS: We identified all Skåne residents aged 35+ who had lived in the region at any point during the period 2006-2019 with no previous OA diagnosis (ICD-10 codes M15-M19) for 8 years prior to inclusion in the study (n = 849,061). We calculated person-years from inclusion until OA diagnosis, death, emigration, or 31 December 2019, whichever occurred first. Combining sex (female, male), education (low, medium, high) and nativity (Swedish, immigrant), we created a variable with 12 strata. Average annual percent changes in age-standardized incidence rates were estimated using joinpoint regression. Changes in the median age-at-diagnosis (year of diagnosis minus birth year), weighted to the mid-2005 Swedish population, were explored. RESULTS: Cumulative age-standardized incidence rates ranged from 116 (95% CI: 111, 121) per 10,000 person-years for immigrant males with low education to 205 (95% CI: 200, 210) for immigrant females with medium education. The estimated average annual percent changes (ranging from 3.4% to 6.1%) were generally similar, with slightly greater variations among immigrants than Swedes. The weighted median age-at-diagnosis was higher for Swedes and low educated people. Immigrant females with low education were the only stratum with a reduction (3 years) in the weighted median age-at-diagnosis over time. Sociodemographic patterns in knee OA incidence were different from patterns for hip OA. CONCLUSIONS: There were few sociodemographic disparities in temporal trends of OA incidence and age-at-diagnosis, suggesting persistent sociodemographic disparities in OA burden in southern Sweden.

@article{fuggle_novel_2025,
	title = {Novel approaches to the stratified management of knee osteoarthritis},
	volume = {21},
	issn = {1759-4804},
	doi = {10.1038/s41584-025-01305-x},
	abstract = {Knee osteoarthritis is a highly prevalent whole-joint disease that is associated with substantial morbidity. If step changes are to be made in the management of knee osteoarthritis, novel patient stratification approaches are needed to identify the most effective treatment for individual patients. Numerous methods for stratifying patients with knee osteoarthritis can be employed; clinical presentation, including co-morbidity and pain phenotype, can influence treatment decisions, and there is a rich history of imaging biomarker use, both from conventional radiographs and, since its development, via MRI, in identifying patients at risk of disease progression, and the latter facilitates the detection of synovitis. The development of novel biochemical biomarkers and the rapid growth of '-omics' technologies provide fresh opportunities to deploy these advances in the stratification of patients with knee osteoarthritis. The health economic landscape in this area is developing, and scoping work has highlighted the need for further studies.},
	language = {eng},
	number = {11},
	journal = {Nature Reviews. Rheumatology},
	author = {Fuggle, Nicholas R. and Chapurlat, Roland and Laslop, Andrea and Al-Daghri, Nasser and Alokail, Majed and Thiyagarajan, Jotheeswaran Amuthavalli and Balkowiec-Iskra, Ewa and Berenbaum, Francis and Bemden, Angie Botto-van and Borg, John-Joseph and Bruyère, Olivier and Burlet, Nansa and Cavalier, Etienne and Rosa, Mario M. and Conaghan, Philip G. and Cooper, Cyrus and Dennison, Elaine M. and Englund, Martin and Im, Gun-Il and Haugen, Ida K. and Hiligsmann, Mickaël and Kurth, Andreas and Lane, Nancy and Lories, Rik and Marlovits, Stefan and Matijevic, Radmila and Mobasheri, Ali and Ormarsdóttir, Sif and Yerro, Maria C. Prieto and Radermecker, Régis P. and Rannou, François and Sepodes, Bruno and Silverman, Stuart and Torre, Carla and Veronese, Nicola and Rizzoli, René and Reginster, Jean-Yves and Harvey, Nicholas C.},
	month = nov,
	year = {2025},
	keywords = {Biomarkers, Disease Progression, Humans, Magnetic Resonance Imaging, Osteoarthritis, Knee},
	pages = {684--695},
}

Knee osteoarthritis is a highly prevalent whole-joint disease that is associated with substantial morbidity. If step changes are to be made in the management of knee osteoarthritis, novel patient stratification approaches are needed to identify the most effective treatment for individual patients. Numerous methods for stratifying patients with knee osteoarthritis can be employed; clinical presentation, including co-morbidity and pain phenotype, can influence treatment decisions, and there is a rich history of imaging biomarker use, both from conventional radiographs and, since its development, via MRI, in identifying patients at risk of disease progression, and the latter facilitates the detection of synovitis. The development of novel biochemical biomarkers and the rapid growth of '-omics' technologies provide fresh opportunities to deploy these advances in the stratification of patients with knee osteoarthritis. The health economic landscape in this area is developing, and scoping work has highlighted the need for further studies.

@article{hada_medial_2025,
	title = {Medial plica is associated with progression of medial meniscus extrusion in middle-aged persons with {Kellgren}-{Lawrence} grade 0: data from the osteoarthritis initiative},
	volume = {20},
	issn = {1749-799X},
	shorttitle = {Medial plica is associated with progression of medial meniscus extrusion in middle-aged persons with {Kellgren}-{Lawrence} grade 0},
	doi = {10.1186/s13018-025-06472-x},
	abstract = {BACKGROUND: Medial plica is a structure with limited understanding of its pathology, but it may be related to the development of medial knee osteoarthritis (OA). We examined the association between medial plica and medial meniscus extrusion (MME), progression of MME, and the risk of early-stage knee OA development in middle-aged persons.
METHODS: A total of 340 subjects with tibiofemoral Kellgren-Lawrence (K/L) grade 0 from the Osteoarthritis Initiative were included. We evaluated magnetic resonance imaging (MRI) data (right knee) at baseline and six years later. At baseline, the severity of medial plica (grade 0-3), extent of MME (grade 0-3) as well as measured MME in mm was determined. After six years, changes in MME (ΔMME), cartilage loss, and the formation of osteophytes were evaluated.
RESULTS: Medial plica (grade ≥ 1) was observed in 280 subjects (82.4\%) at baseline, of whom 13 subjects had grade 3 plica. The MME was 1.7 ± 0.8 mm at baseline and 2.1 ± 0.9 mm after 6 years. Progression of MME was observed in 83 subjects (24.5\%) after 6 years. The cartilage loss after 6 years in subjects with medial plica grade ≥ 1 at baseline was greater than that in subjects without medial plica (Δcartilage score 2.9 ± 2.8 vs. 2.2 ± 3.0, p = 0.01), although the difference was borderline when analyzed across all plica grades (p = 0.05). The ΔMME was greater for higher grades of medial plica at baseline (p = 0.01). Subjects with medial plica grade ≥ 1 had a higher risk of progression of MME grade (odds ratio [OR] 2.1, 95\% CI 1.0-4.5, p = 0.04), but this was not significant for grade ≥ 2 in sensitivity analysis (OR 1.2, p = 0.50). Progression of K/L grade was observed only for medial plica grade ≥ 2 (OR 2.1, 95\% CI 1.1-4.2, p = 0.03), but not for grade ≥ 1.
CONCLUSION: In middle-aged persons with K/L grade 0, the presence of medial plica-particularly higher-grade lesions-was associated with progression of MME and cartilage loss, and grade ≥ 2 lesions were additionally associated with radiographic progression of knee OA.},
	language = {eng},
	number = {1},
	journal = {Journal of Orthopaedic Surgery and Research},
	author = {Hada, Shinnosuke and Kaneko, Haruka and Aoki, Takako and Nojiri, Shuko and Englund, Martin and Ishijima, Muneaki},
	month = nov,
	year = {2025},
	keywords = {Aged, Disease Progression, Female, Humans, Knee osteoarthritis, Magnetic Resonance Imaging, Magnetic resonance imaging, Male, Medial plica, Menisci, Tibial, Meniscus, Meniscus extrusion, Middle Aged, Osteoarthritis, Knee, Osteophytes, Severity of Illness Index, Tibial Meniscus Injuries},
	pages = {1030},
}

BACKGROUND: Medial plica is a structure with limited understanding of its pathology, but it may be related to the development of medial knee osteoarthritis (OA). We examined the association between medial plica and medial meniscus extrusion (MME), progression of MME, and the risk of early-stage knee OA development in middle-aged persons. METHODS: A total of 340 subjects with tibiofemoral Kellgren-Lawrence (K/L) grade 0 from the Osteoarthritis Initiative were included. We evaluated magnetic resonance imaging (MRI) data (right knee) at baseline and six years later. At baseline, the severity of medial plica (grade 0-3), extent of MME (grade 0-3) as well as measured MME in mm was determined. After six years, changes in MME (ΔMME), cartilage loss, and the formation of osteophytes were evaluated. RESULTS: Medial plica (grade ≥ 1) was observed in 280 subjects (82.4%) at baseline, of whom 13 subjects had grade 3 plica. The MME was 1.7 ± 0.8 mm at baseline and 2.1 ± 0.9 mm after 6 years. Progression of MME was observed in 83 subjects (24.5%) after 6 years. The cartilage loss after 6 years in subjects with medial plica grade ≥ 1 at baseline was greater than that in subjects without medial plica (Δcartilage score 2.9 ± 2.8 vs. 2.2 ± 3.0, p = 0.01), although the difference was borderline when analyzed across all plica grades (p = 0.05). The ΔMME was greater for higher grades of medial plica at baseline (p = 0.01). Subjects with medial plica grade ≥ 1 had a higher risk of progression of MME grade (odds ratio [OR] 2.1, 95% CI 1.0-4.5, p = 0.04), but this was not significant for grade ≥ 2 in sensitivity analysis (OR 1.2, p = 0.50). Progression of K/L grade was observed only for medial plica grade ≥ 2 (OR 2.1, 95% CI 1.1-4.2, p = 0.03), but not for grade ≥ 1. CONCLUSION: In middle-aged persons with K/L grade 0, the presence of medial plica-particularly higher-grade lesions-was associated with progression of MME and cartilage loss, and grade ≥ 2 lesions were additionally associated with radiographic progression of knee OA.

@article{vinblad_association_2025,
	title = {Association of type 2 diabetes with reoperation, adverse events and mortality after hip and knee replacement: a {Swedish} register-based study including 109 938 hip and 80 897 knee replacements},
	volume = {15},
	issn = {2044-6055},
	shorttitle = {Association of type 2 diabetes with reoperation, adverse events and mortality after hip and knee replacement},
	doi = {10.1136/bmjopen-2024-096717},
	abstract = {OBJECTIVE: Type 2 diabetes mellitus (T2DM) and osteoarthritis (OA) are globally prevalent chronic diseases that affect millions of individuals in ageing populations. Hip and knee replacements are well established and effective treatments in patients suffering from end-stage OA. Understanding how T2DM influences the outcomes of these surgeries is important for optimising patient care and improving surgical results. This study aimed to explore the association of T2DM with reoperation (regardless of the reason), adverse events (AEs) and mortality after primary hip and knee replacement surgery.
DESIGN: Observational study based on prospectively collected registry data analysed retrospectively.
SETTING AND PARTICIPANTS: Data from several Swedish national quality registers and health data registers were used to create a study database. 109 938 and 80 897 primary hip and knee replacements due to OA, performed between 2008 and 2019 (hip) and 2009 and 2018 (knee), were included in the study.
OUTCOME MEASURES: The risk of complications, such as reoperation, AEs and mortality, was investigated by estimating HRs using Cox regression, and OR using logistic regression, unadjusted and adjusted for confounding factors, such as patient characteristics, socioeconomic status and comorbidities, and mediators, such as surgical factors.
RESULTS: Adjusted multivariable Cox-regression analysis showed no T2DM-associated risk of reoperation after hip or knee replacement, adjusted HR 1.10 (95\% CI 0.99 to 1.23) and 1.09 (95\% CI 0.96 to 1.24), respectively, while T2DM was associated with increased risk of death after hip and knee replacement, adjusted HR 1.40 (95\% CI 1.34 to 1.47) and 1.38 (95\% CI 1.31 to 1.45). Adjusted logistic regression analysis showed T2DM-associated increase of reoperation within 90 days (OR 1.23 (95\% CI 1.05 to 1.43)) and increased mortality within 90 days (OR 1.42 (95\% CI 1.01 to 1.95)) following hip replacement; however, this was not the case after knee replacement, OR 1.08 (95\% CI 0.85 to 1.36) for reoperation and OR 1.29 (95\% CI 0.84 to 1.94) for mortality. Several factors closely linked with T2DM, such as body-mass index and comorbidities, were identified as important when assessing risk of reoperation and mortality. Regarding AEs within 30 and 90 days, very slight but not statistically significant T2DM-associated increases were seen after either hip replacement, OR 1.01 (95\% CI 0.91 to 1.11) and 1.07 (95\% CI 0.98 to 1.16) or after knee replacement, OR 1.05 (95\% CI 0.93 to 1.17) and 1.08 (95\% CI 0.98 to 1.19).
CONCLUSION: The observed risk of reoperation suggests that T2DM alone was not a strong justification to advise against hip or knee replacement in individuals with T2DM deemed eligible for joint replacement. The T2DM-associated increased mortality after hip and knee replacement is challenging to interpret, as T2DM itself without undergoing hip or knee replacement surgery is associated with increased mortality.},
	language = {eng},
	number = {9},
	journal = {BMJ open},
	author = {Vinblad, Johanna and Bülow, Erik and Nyberg, Fredrik and Eeg-Olofsson, Katarina and W-Dahl, Annette and Limbäck, Gunilla and Englund, Martin and Abbott, Allan and Dell'Isola, Andrea and Rolfson, Ola},
	month = sep,
	year = {2025},
	keywords = {Adverse events, Aged, Aged, 80 and over, Arthroplasty, Replacement, Hip, Arthroplasty, Replacement, Knee, Diabetes Mellitus, Type 2, Female, Hip, Humans, Knee, Male, Middle Aged, Mortality, Osteoarthritis, Hip, Osteoarthritis, Knee, Postoperative Complications, REGISTRIES, Registries, Reoperation, Retrospective Studies, Risk Factors, Sweden},
	pages = {e096717},
}

OBJECTIVE: Type 2 diabetes mellitus (T2DM) and osteoarthritis (OA) are globally prevalent chronic diseases that affect millions of individuals in ageing populations. Hip and knee replacements are well established and effective treatments in patients suffering from end-stage OA. Understanding how T2DM influences the outcomes of these surgeries is important for optimising patient care and improving surgical results. This study aimed to explore the association of T2DM with reoperation (regardless of the reason), adverse events (AEs) and mortality after primary hip and knee replacement surgery. DESIGN: Observational study based on prospectively collected registry data analysed retrospectively. SETTING AND PARTICIPANTS: Data from several Swedish national quality registers and health data registers were used to create a study database. 109 938 and 80 897 primary hip and knee replacements due to OA, performed between 2008 and 2019 (hip) and 2009 and 2018 (knee), were included in the study. OUTCOME MEASURES: The risk of complications, such as reoperation, AEs and mortality, was investigated by estimating HRs using Cox regression, and OR using logistic regression, unadjusted and adjusted for confounding factors, such as patient characteristics, socioeconomic status and comorbidities, and mediators, such as surgical factors. RESULTS: Adjusted multivariable Cox-regression analysis showed no T2DM-associated risk of reoperation after hip or knee replacement, adjusted HR 1.10 (95% CI 0.99 to 1.23) and 1.09 (95% CI 0.96 to 1.24), respectively, while T2DM was associated with increased risk of death after hip and knee replacement, adjusted HR 1.40 (95% CI 1.34 to 1.47) and 1.38 (95% CI 1.31 to 1.45). Adjusted logistic regression analysis showed T2DM-associated increase of reoperation within 90 days (OR 1.23 (95% CI 1.05 to 1.43)) and increased mortality within 90 days (OR 1.42 (95% CI 1.01 to 1.95)) following hip replacement; however, this was not the case after knee replacement, OR 1.08 (95% CI 0.85 to 1.36) for reoperation and OR 1.29 (95% CI 0.84 to 1.94) for mortality. Several factors closely linked with T2DM, such as body-mass index and comorbidities, were identified as important when assessing risk of reoperation and mortality. Regarding AEs within 30 and 90 days, very slight but not statistically significant T2DM-associated increases were seen after either hip replacement, OR 1.01 (95% CI 0.91 to 1.11) and 1.07 (95% CI 0.98 to 1.16) or after knee replacement, OR 1.05 (95% CI 0.93 to 1.17) and 1.08 (95% CI 0.98 to 1.19). CONCLUSION: The observed risk of reoperation suggests that T2DM alone was not a strong justification to advise against hip or knee replacement in individuals with T2DM deemed eligible for joint replacement. The T2DM-associated increased mortality after hip and knee replacement is challenging to interpret, as T2DM itself without undergoing hip or knee replacement surgery is associated with increased mortality.

@article{recenti_association_2025,
	title = {Association between metabolic conditions, physical activity and self-efficacy before and after a first-line exercise and education intervention for osteoarthritis: a longitudinal register study using the {SOAD} cohort},
	volume = {11},
	issn = {2056-5933},
	shorttitle = {Association between metabolic conditions, physical activity and self-efficacy before and after a first-line exercise and education intervention for osteoarthritis},
	doi = {10.1136/rmdopen-2025-005804},
	abstract = {OBJECTIVES: To investigate the association of diabetes, hypertension and overweight/obesity with physical activity (PA), self-efficacy for pain and self-efficacy for other symptoms before and after a 6- week exercise and education intervention for knee and hip osteoarthritis (OA), and to assess outcome disparities based on metabolic health.
METHODS: Register-based cohort study using the Swedish Osteoarthritis and Diabetes cohort. We used Body Mass Index, medical records and medication dispensation to define overweight/obesity, hypertension and diabetes at baseline (exposures). PA was self-reported (weekly minutes), and self-efficacy was measured using the 'Arthritis Self-Efficacy Scale' (ASES) (score 10-100) (outcomes). We used linear mixed-effect models to estimate associations between exposures and outcomes, adjusted for confounders.
RESULTS: We included 80 893 individuals with knee or hip OA. Those with metabolic conditions consistently showed lower PA and self-efficacy, with baseline disparities persisting after the intervention, particularly when all three conditions coexisted (PA difference: baseline 107 min [95\% CI: 97; 118], 3-month 97 [86; 108], 12-month 109 [95; 123]; ASES-pain difference: baseline 5.6 [3.9; 7.3], 3-month 5.9 [4.1; 7.7], 12-month 8.2 [6.1; 10.4]; ASES-other symptoms difference: baseline 6.1 [4.6; 7.7], 3-month 6.4 [4.8; 8.0], 12-month 8.2 [6.3; 10.1]).
CONCLUSIONS: Metabolic conditions were associated with lower PA and self-efficacy, with differences increasing with the number of co-existing conditions. The baseline disparities associated with metabolic conditions persisted after the intervention, with both groups showing improvement at 3 months but reverting to baseline by 12 months. This suggests that current guideline-based interventions for OA may not reduce long-term disparities related to metabolic conditions.},
	language = {eng},
	number = {3},
	journal = {RMD open},
	author = {Recenti, Filippo and Battista, Simone and Lohmander, Stefan and Vinblad, Johanna and Kiadaliri, Ali and Abbott, Allan and Rolfson, Ola and Englund, Martin and Testa, Marco and Dell'Isola, Andrea},
	month = sep,
	year = {2025},
	keywords = {Aged, Exercise, Exercise Therapy, Female, Humans, Hypertension, Longitudinal Studies, Male, Middle Aged, Osteoarthritis, Osteoarthritis, Hip, Osteoarthritis, Knee, Patient Education as Topic, Registries, Rehabilitation, Self Efficacy, Sweden},
	pages = {e005804},
}

OBJECTIVES: To investigate the association of diabetes, hypertension and overweight/obesity with physical activity (PA), self-efficacy for pain and self-efficacy for other symptoms before and after a 6- week exercise and education intervention for knee and hip osteoarthritis (OA), and to assess outcome disparities based on metabolic health. METHODS: Register-based cohort study using the Swedish Osteoarthritis and Diabetes cohort. We used Body Mass Index, medical records and medication dispensation to define overweight/obesity, hypertension and diabetes at baseline (exposures). PA was self-reported (weekly minutes), and self-efficacy was measured using the 'Arthritis Self-Efficacy Scale' (ASES) (score 10-100) (outcomes). We used linear mixed-effect models to estimate associations between exposures and outcomes, adjusted for confounders. RESULTS: We included 80 893 individuals with knee or hip OA. Those with metabolic conditions consistently showed lower PA and self-efficacy, with baseline disparities persisting after the intervention, particularly when all three conditions coexisted (PA difference: baseline 107 min [95% CI: 97; 118], 3-month 97 [86; 108], 12-month 109 [95; 123]; ASES-pain difference: baseline 5.6 [3.9; 7.3], 3-month 5.9 [4.1; 7.7], 12-month 8.2 [6.1; 10.4]; ASES-other symptoms difference: baseline 6.1 [4.6; 7.7], 3-month 6.4 [4.8; 8.0], 12-month 8.2 [6.3; 10.1]). CONCLUSIONS: Metabolic conditions were associated with lower PA and self-efficacy, with differences increasing with the number of co-existing conditions. The baseline disparities associated with metabolic conditions persisted after the intervention, with both groups showing improvement at 3 months but reverting to baseline by 12 months. This suggests that current guideline-based interventions for OA may not reduce long-term disparities related to metabolic conditions.

@article{lonsjo_altered_2025,
	title = {Altered co-expression patterns of synovial fluid proteins related to the immune system and extracellular matrix organization in late stage {OA}, compared to non-{OA} controls},
	volume = {16},
	issn = {1664-3224},
	doi = {10.3389/fimmu.2025.1523103},
	abstract = {OBJECTIVE: Synovial fluid contains proteins that may have been released from surrounding tissues, our aim was to gain new insights into the proteomic profiles of human synovial fluid in knees with and without osteoarthritis (OA).
METHODS: We used synovial fluid from 11 patients with end-stage medial compartment knee OA, aspirated during total knee replacement, and from 13 deceased donors who had no prior history of knee OA (healthy controls). These samples were analyzed using high-multiplex immunoassays Olink®. The differential expression of proteins between the groups was analyzed using a linear mixed effects model. The linear associations between pairs of protein expressions were estimated with a linear regression model.
RESULTS: We found that almost half of the detected proteins were differentially expressed between the OA and non-OA controls. The proteins that were most elevated in the OA group compared to controls were tartrate-resistant acid phosphatase type 5 (fold change 10.6, 95\% CI [6.6-17.0]), plasminogen activator inhibitor 1 (5.0 [3.1, 8.0]), coagulation factor XI (4.3 [2.6-6.8]) and urokinase-type plasminogen activator (4.3 [2.3-6.8]). The proteins with lower levels in OA compared to controls were fatty acid-binding protein, adipocyte (0.03 [0.02-0.05]), myocilin (0.05 [0.03-0.08]) and carbonic anhydrase 3 (0.14 [0.09-0.23]). The protein-protein co-expression analysis suggests an overall lower number of protein pairs that show co-expression in OA.
CONCLUSION: There is a substantial change in protein abundance in synovial fluid in end-stage knee OA, suggesting that global joint homeostasis is severely deranged. Our findings suggest altered co-expression between the immune response and extracellular matrix organization in end-stage knee OA, in comparison to non-OA controls.},
	language = {eng},
	journal = {Frontiers in Immunology},
	author = {Lönsjö, Jenny and Rydén, Martin and Turkiewicz, Aleksandra and Hughes, Velocity and Tjörnstand, Jon and Önnerfjord, Patrik and Englund, Martin and Ali, Neserin},
	year = {2025},
	keywords = {Aged, Biomarkers, Case-Control Studies, Extracellular Matrix, Female, Humans, Male, Middle Aged, Olink, Osteoarthritis, Knee, Proteomics, Synovial Fluid, osteoarthritis, protein-protein coexpression, proteomics, synovial fluid},
	pages = {1523103},
}

OBJECTIVE: Synovial fluid contains proteins that may have been released from surrounding tissues, our aim was to gain new insights into the proteomic profiles of human synovial fluid in knees with and without osteoarthritis (OA). METHODS: We used synovial fluid from 11 patients with end-stage medial compartment knee OA, aspirated during total knee replacement, and from 13 deceased donors who had no prior history of knee OA (healthy controls). These samples were analyzed using high-multiplex immunoassays Olink®. The differential expression of proteins between the groups was analyzed using a linear mixed effects model. The linear associations between pairs of protein expressions were estimated with a linear regression model. RESULTS: We found that almost half of the detected proteins were differentially expressed between the OA and non-OA controls. The proteins that were most elevated in the OA group compared to controls were tartrate-resistant acid phosphatase type 5 (fold change 10.6, 95% CI [6.6-17.0]), plasminogen activator inhibitor 1 (5.0 [3.1, 8.0]), coagulation factor XI (4.3 [2.6-6.8]) and urokinase-type plasminogen activator (4.3 [2.3-6.8]). The proteins with lower levels in OA compared to controls were fatty acid-binding protein, adipocyte (0.03 [0.02-0.05]), myocilin (0.05 [0.03-0.08]) and carbonic anhydrase 3 (0.14 [0.09-0.23]). The protein-protein co-expression analysis suggests an overall lower number of protein pairs that show co-expression in OA. CONCLUSION: There is a substantial change in protein abundance in synovial fluid in end-stage knee OA, suggesting that global joint homeostasis is severely deranged. Our findings suggest altered co-expression between the immune response and extracellular matrix organization in end-stage knee OA, in comparison to non-OA controls.

@article{king_multi-centre_2025,
	title = {Multi-centre modified {Delphi} exercise to identify candidate items for classifying early-stage symptomatic knee osteoarthritis},
	volume = {33},
	issn = {1522-9653},
	doi = {10.1016/j.joca.2024.10.016},
	abstract = {OBJECTIVE: To generate a list of candidate items potentially useful for discriminating individuals with Early-stage Symptomatic Knee Osteoarthritis (EsSKOA) from those with other conditions and from established osteoarthritis (OA), and to reduce this list based on expert consensus.
DESIGN: We conducted a three-round online international modified Delphi exercise with OA clinicians and researchers ("OA experts"). In Round 1, participants reviewed 84 candidate items and nominated additional item(s) potentially useful for EsSKOA classification; those nominated by ≥3 participants were added. In Round 2, participants rated perceived usefulness of 108 items (1 [not at all useful] to 9 [extremely useful]). In Round 3, participants could revise their ratings after reviewing Round 2 group median and quartiles. Following Round 3, we retained items with a median usefulness score {\textgreater}5 and ≥33.3\% of participants categorised the item as useful (7 to 9), overall and in subgroup analysis by clinician field.
RESULTS: There were 128 participants in Round 1 and 113 (88\%) completed all rounds. We retained 77 items that spanned multiple domains (demographics, symptoms, physical exam, performance-based measures, imaging, laboratory investigations, and gross inspection/arthroscopy). Highly rated items included (median usefulness score): prior knee joint injury (8), diagnosis of OA in a different joint (7), and activity-related knee pain (7). The interquartile range was most often 3.
CONCLUSION: We identified 77 items that OA experts consider potentially useful for EsSKOA classification. The results highlight experts' uncertainty around item usefulness. Next, candidate items will be further assessed and reduced using data-driven and multicriteria decision analysis methods.},
	language = {eng},
	number = {1},
	journal = {Osteoarthritis and Cartilage},
	author = {King, L. K. and Liew, J. W. and Mahmoudian, A. and Wang, Q. and Jansen, N. E. J. and Stanaitis, I. and Hung, V. and Berenbaum, F. and Das, S. and Ding, C. and Emery, C. A. and Filbay, S. R. and Hochberg, M. C. and Ishijima, M. and Kloppenburg, M. and Lane, N. E. and Losina, E. and Mobasheri, A. and Turkiewicz, A. and Runhaar, J. and Haugen, I. K. and Appleton, C. T. and Lohmander, L. S. and Englund, M. and Neogi, T. and Hawker, G. A. and {OARSI Early-stage Symptomatic Knee Osteoarthritis Initiative}},
	month = jan,
	year = {2025},
	keywords = {Aged, Classification criteria, Consensus, Delphi, Delphi Technique, Early-stage, Female, Humans, Knee osteoarthritis, Male, Middle Aged, Osteoarthritis, Knee, Severity of Illness Index, Symptoms},
	pages = {155--165},
}

OBJECTIVE: To generate a list of candidate items potentially useful for discriminating individuals with Early-stage Symptomatic Knee Osteoarthritis (EsSKOA) from those with other conditions and from established osteoarthritis (OA), and to reduce this list based on expert consensus. DESIGN: We conducted a three-round online international modified Delphi exercise with OA clinicians and researchers ("OA experts"). In Round 1, participants reviewed 84 candidate items and nominated additional item(s) potentially useful for EsSKOA classification; those nominated by ≥3 participants were added. In Round 2, participants rated perceived usefulness of 108 items (1 [not at all useful] to 9 [extremely useful]). In Round 3, participants could revise their ratings after reviewing Round 2 group median and quartiles. Following Round 3, we retained items with a median usefulness score \textgreater5 and ≥33.3% of participants categorised the item as useful (7 to 9), overall and in subgroup analysis by clinician field. RESULTS: There were 128 participants in Round 1 and 113 (88%) completed all rounds. We retained 77 items that spanned multiple domains (demographics, symptoms, physical exam, performance-based measures, imaging, laboratory investigations, and gross inspection/arthroscopy). Highly rated items included (median usefulness score): prior knee joint injury (8), diagnosis of OA in a different joint (7), and activity-related knee pain (7). The interquartile range was most often 3. CONCLUSION: We identified 77 items that OA experts consider potentially useful for EsSKOA classification. The results highlight experts' uncertainty around item usefulness. Next, candidate items will be further assessed and reduced using data-driven and multicriteria decision analysis methods.

@article{nilsson_varus_2025,
	title = {Varus alignment of the hip and knee 2 years after anterior cruciate ligament injury is associated with medial tibiofemoral osteoarthritis 3 years later},
	volume = {12},
	issn = {2197-1153},
	doi = {10.1002/jeo2.70143},
	abstract = {PURPOSE: To investigate if hip and knee alignment assessed 2 years after anterior cruciate ligament (ACL) injury is associated with compartment-specific radiographic knee osteoarthritis (OA) 3 years later.
METHODS: An exploratory analysis was conducted in the knee ACL, nonsurgical versus surgical treatment (KANON) trial (ISRCTN84752559); 115 subjects with acute ACL injury were assessed at the 2-year follow-up; full-limb images of the injured leg were acquired, and the neck-shaft angle (NSA) and hip-knee-ankle angle (HKA) were measured. At the 5-year follow-up, weight-bearing tibiofemoral and patellofemoral radiographs were obtained. Radiographs were graded according to the OA Research Society International Atlas and Radiographic OA was defined as approximating Kellgren \& Lawrence grade 2 or worse. Analysis of covariance adjusting for sex, age, body mass index, randomization and partial meniscectomy recorded at the 2-year follow-up was performed.
RESULTS: In patients who had developed medial tibiofemoral OA at the 5-year follow-up, the NSA and the HKA at the 2-year follow-up were smaller (NSA, mean difference = -4.6° [95\% confidence interval \{CI\} -7.9° to -1.1°]; HKA, mean difference = -2.3° [95\% CI -4.2° to -0.4°]). No association was observed between the NSA or HKA at the 2-year follow-up and lateral tibiofemoral OA, nor patellofemoral OA at the 5-year follow-up.
CONCLUSION: A smaller NSA and HKA angle of the ACL injured leg (i.e., more varus hip and varus knee alignment) 2 years after the injury was associated with medial tibiofemoral radiographic OA 3 years later.
LEVEL OF EVIDENCE: Level II exploratory post hoc analysis of an RCT.},
	language = {eng},
	number = {1},
	journal = {Journal of Experimental Orthopaedics},
	author = {Nilsson, Henrik and Englund, Martin and Frobell, Richard and Lohmander, L. Stefan and Struglics, André and Swärd, Per},
	month = jan,
	year = {2025},
	keywords = {alignment, anterior cruciate ligament, hip knee ankle angle, neck‐shaft angle, osteoarthritis},
	pages = {e70143},
}

PURPOSE: To investigate if hip and knee alignment assessed 2 years after anterior cruciate ligament (ACL) injury is associated with compartment-specific radiographic knee osteoarthritis (OA) 3 years later. METHODS: An exploratory analysis was conducted in the knee ACL, nonsurgical versus surgical treatment (KANON) trial (ISRCTN84752559); 115 subjects with acute ACL injury were assessed at the 2-year follow-up; full-limb images of the injured leg were acquired, and the neck-shaft angle (NSA) and hip-knee-ankle angle (HKA) were measured. At the 5-year follow-up, weight-bearing tibiofemoral and patellofemoral radiographs were obtained. Radiographs were graded according to the OA Research Society International Atlas and Radiographic OA was defined as approximating Kellgren & Lawrence grade 2 or worse. Analysis of covariance adjusting for sex, age, body mass index, randomization and partial meniscectomy recorded at the 2-year follow-up was performed. RESULTS: In patients who had developed medial tibiofemoral OA at the 5-year follow-up, the NSA and the HKA at the 2-year follow-up were smaller (NSA, mean difference = -4.6° [95% confidence interval \CI\ -7.9° to -1.1°]; HKA, mean difference = -2.3° [95% CI -4.2° to -0.4°]). No association was observed between the NSA or HKA at the 2-year follow-up and lateral tibiofemoral OA, nor patellofemoral OA at the 5-year follow-up. CONCLUSION: A smaller NSA and HKA angle of the ACL injured leg (i.e., more varus hip and varus knee alignment) 2 years after the injury was associated with medial tibiofemoral radiographic OA 3 years later. LEVEL OF EVIDENCE: Level II exploratory post hoc analysis of an RCT.

@article{turkiewicz_physical_2025,
	title = {Physical health in young males and risk of chronic musculoskeletal, cardiovascular, and respiratory diseases by middle age: {A} population-based cohort study},
	volume = {22},
	issn = {1549-1676},
	shorttitle = {Physical health in young males and risk of chronic musculoskeletal, cardiovascular, and respiratory diseases by middle age},
	doi = {10.1371/journal.pmed.1004517},
	abstract = {BACKGROUND: Cardiovascular, respiratory, and musculoskeletal disease are among the leading causes of disability in middle-aged and older people. Health and lifestyle factors in youth have known associations with cardiovascular or respiratory disease in adulthood, but largely unknown associations with musculoskeletal disease.
METHODS AND FINDINGS: We included approximately 40,000 18-year-old Swedish males, who completed their conscription examination in 1969 to 1970, followed up until age of 60 years. Exposures of interest were physical health: body mass and height, blood pressure, pulse at rest, muscle strength, cardiorespiratory fitness, and hematocrit; self-reported lifestyle: smoking, alcohol, and drug use; self-reported health: overall, headache and gastrointestinal. We followed the participants through the Swedish National Patient Register for incidence of common musculoskeletal (osteoarthritis, back pain, shoulder lesions, joint pain, myalgia), cardiovascular (ischemic heart disease, atrial fibrillation), and respiratory diseases (asthma, chronic obstructive pulmonary disease, bronchitis). We analyzed the associations using general estimating equations Poisson regression with all exposures included in one model and adjusted for parental education and occupation. We found that higher body mass was associated with higher risk of musculoskeletal (risk ratio [RR] per 1 standard deviation [SD] 1.12 [95\% confidence interval, CI 1.09, 1.16]), cardiovascular (RR 1.22 [95\% CI 1.17, 1.27] per 1 SD) and respiratory diseases (RR 1.14 [95\% CI 1.05, 1.23] per 1 SD). Notably, higher muscle strength and cardiorespiratory fitness were associated with higher risk of musculoskeletal disease (RRs 1.08 [95\% CI 1.05, 1.11] and 1.06 [95\% CI 1.01, 1.12] per 1 SD difference in exposure), while higher cardiorespiratory fitness was protective against both cardiovascular and respiratory diseases (RRs 0.91 [95\% CI 0.85, 0.98] and 0.85 [95\% CI 0.73, 0.97] per 1 SD exposure, respectively). We confirmed the adverse effects of smoking, with risk ratios when comparing 11+ cigarettes per day to non-smoking of 1.14 (95\% CI 1.06, 1.22) for musculoskeletal, 1.58 (95\% CI 1.44, 1.74) for cardiovascular, and 1.93 (95\% CI 1.60, 2.32) for respiratory diseases. Self-reported headache (category "often" compared to "never") was associated with musculoskeletal diseases (RR 1.38 [95\% CI 1.21, 1.58]) and cardiovascular diseases (RR 1.29 [95\% CI 1.07, 1.56]), but had an inconclusive association with respiratory diseases (RR 1.13 [95\% CI 0.79, 1.60]). No large consistent associations were found for other exposures. The most notable associations with specific musculoskeletal conditions were for cardiorespiratory fitness and osteoarthritis (RR 1.23 [95\% CI 1.15, 1.32] per 1 SD) and for muscle strength and back pain (RR 1.18 [95\% CI 1.12, 1.24] per 1 SD) or shoulder diseases (RR 1.27 [95\% CI 1.19, 1.36] per 1 SD). The main limitations include lack of adjustment for genetic factors and environmental exposures from childhood, and that the register data were available for males only.
CONCLUSIONS: While high body mass was a risk factor for all 3 studied groups of diseases, high cardiorespiratory fitness and high muscle strength in youth were associated with increased risk of musculoskeletal disease in middle age. We speculate that these associations are mediated by chronic overload or acute trauma.},
	language = {eng},
	number = {1},
	journal = {PLoS medicine},
	author = {Turkiewicz, Aleksandra and Magnusson, Karin and Timpka, Simon and Kiadaliri, Ali and Dell'Isola, Andrea and Englund, Martin},
	month = jan,
	year = {2025},
	keywords = {Adolescent, Adult, Body Mass Index, Cardiorespiratory Fitness, Cardiovascular Diseases, Chronic Disease, Cohort Studies, Health Status, Humans, Incidence, Life Style, Male, Middle Aged, Musculoskeletal Diseases, Respiratory Tract Diseases, Risk Factors, Sweden, Young Adult},
	pages = {e1004517},
}

BACKGROUND: Cardiovascular, respiratory, and musculoskeletal disease are among the leading causes of disability in middle-aged and older people. Health and lifestyle factors in youth have known associations with cardiovascular or respiratory disease in adulthood, but largely unknown associations with musculoskeletal disease. METHODS AND FINDINGS: We included approximately 40,000 18-year-old Swedish males, who completed their conscription examination in 1969 to 1970, followed up until age of 60 years. Exposures of interest were physical health: body mass and height, blood pressure, pulse at rest, muscle strength, cardiorespiratory fitness, and hematocrit; self-reported lifestyle: smoking, alcohol, and drug use; self-reported health: overall, headache and gastrointestinal. We followed the participants through the Swedish National Patient Register for incidence of common musculoskeletal (osteoarthritis, back pain, shoulder lesions, joint pain, myalgia), cardiovascular (ischemic heart disease, atrial fibrillation), and respiratory diseases (asthma, chronic obstructive pulmonary disease, bronchitis). We analyzed the associations using general estimating equations Poisson regression with all exposures included in one model and adjusted for parental education and occupation. We found that higher body mass was associated with higher risk of musculoskeletal (risk ratio [RR] per 1 standard deviation [SD] 1.12 [95% confidence interval, CI 1.09, 1.16]), cardiovascular (RR 1.22 [95% CI 1.17, 1.27] per 1 SD) and respiratory diseases (RR 1.14 [95% CI 1.05, 1.23] per 1 SD). Notably, higher muscle strength and cardiorespiratory fitness were associated with higher risk of musculoskeletal disease (RRs 1.08 [95% CI 1.05, 1.11] and 1.06 [95% CI 1.01, 1.12] per 1 SD difference in exposure), while higher cardiorespiratory fitness was protective against both cardiovascular and respiratory diseases (RRs 0.91 [95% CI 0.85, 0.98] and 0.85 [95% CI 0.73, 0.97] per 1 SD exposure, respectively). We confirmed the adverse effects of smoking, with risk ratios when comparing 11+ cigarettes per day to non-smoking of 1.14 (95% CI 1.06, 1.22) for musculoskeletal, 1.58 (95% CI 1.44, 1.74) for cardiovascular, and 1.93 (95% CI 1.60, 2.32) for respiratory diseases. Self-reported headache (category "often" compared to "never") was associated with musculoskeletal diseases (RR 1.38 [95% CI 1.21, 1.58]) and cardiovascular diseases (RR 1.29 [95% CI 1.07, 1.56]), but had an inconclusive association with respiratory diseases (RR 1.13 [95% CI 0.79, 1.60]). No large consistent associations were found for other exposures. The most notable associations with specific musculoskeletal conditions were for cardiorespiratory fitness and osteoarthritis (RR 1.23 [95% CI 1.15, 1.32] per 1 SD) and for muscle strength and back pain (RR 1.18 [95% CI 1.12, 1.24] per 1 SD) or shoulder diseases (RR 1.27 [95% CI 1.19, 1.36] per 1 SD). The main limitations include lack of adjustment for genetic factors and environmental exposures from childhood, and that the register data were available for males only. CONCLUSIONS: While high body mass was a risk factor for all 3 studied groups of diseases, high cardiorespiratory fitness and high muscle strength in youth were associated with increased risk of musculoskeletal disease in middle age. We speculate that these associations are mediated by chronic overload or acute trauma.

@article{berg_arthroscopic_2025,
	title = {Arthroscopic partial meniscectomy versus exercise therapy for degenerative meniscal tears: 10-year follow-up of the {OMEX} randomised controlled trial},
	volume = {59},
	issn = {1473-0480},
	shorttitle = {Arthroscopic partial meniscectomy versus exercise therapy for degenerative meniscal tears},
	doi = {10.1136/bjsports-2024-108644},
	abstract = {OBJECTIVE: To evaluate radiographic knee osteoarthritis (OA) progression, development of knee OA, patient-reported outcomes and knee muscle strength at 10-year follow-up after arthroscopic partial meniscectomy (APM) or exercise therapy for degenerative meniscal tears.
METHODS: Randomised controlled trial including 140 participants, with a degenerative meniscal tear and no or minimal radiographic OA changes. Participants were randomised to either APM or 12 weeks of exercise therapy (1:1 ratio). The primary outcome was knee OA progression assessed by the Osteoarthritis Research Society International (OARSI) atlas sum score (sum of medial and lateral compartment joint space narrowing and osteophyte score). Secondary outcomes included incidence of radiographic and symptomatic knee OA, patient-reported pain and knee function and isokinetic knee muscle strength.
RESULTS: The adjusted mean difference in change in the OARSI sum score was 0.39 (95\% CI -0.19 to 0.97), with more progression in the APM group. The incidence of radiographic knee OA was 23\% in the APM group and 20\% in the exercise group (adjusted risk difference 3\% (95\% CI -13\% to 19\%)). No clinically relevant differences were found in patient-reported outcomes or isokinetic knee muscle strength.
CONCLUSION: No differences in radiographic knee OA progression and comparable rates of knee OA development were observed 10 years following APM and exercise therapy for degenerative meniscal tears. Both treatments were associated with improved patient-reported pain and knee function.
TRIAL REGISTRATION NUMBER: NCT01002794.},
	language = {eng},
	number = {2},
	journal = {British Journal of Sports Medicine},
	author = {Berg, Bjørnar and Roos, Ewa M. and Englund, Martin and Kise, Nina Jullum and Engebretsen, Lars and Eftang, Cathrine Nørstad and Risberg, May Arna},
	month = jan,
	year = {2025},
	keywords = {Adult, Aged, Arthroscopy, Disease Progression, Exercise Therapy, Female, Follow-Up Studies, Humans, Knee Joint, Male, Meniscectomy, Middle Aged, Muscle Strength, Osteoarthritis, Knee, Patient Reported Outcome Measures, Radiography, Tibial Meniscus Injuries, arthroscopy, exercise},
	pages = {91--98},
}

OBJECTIVE: To evaluate radiographic knee osteoarthritis (OA) progression, development of knee OA, patient-reported outcomes and knee muscle strength at 10-year follow-up after arthroscopic partial meniscectomy (APM) or exercise therapy for degenerative meniscal tears. METHODS: Randomised controlled trial including 140 participants, with a degenerative meniscal tear and no or minimal radiographic OA changes. Participants were randomised to either APM or 12 weeks of exercise therapy (1:1 ratio). The primary outcome was knee OA progression assessed by the Osteoarthritis Research Society International (OARSI) atlas sum score (sum of medial and lateral compartment joint space narrowing and osteophyte score). Secondary outcomes included incidence of radiographic and symptomatic knee OA, patient-reported pain and knee function and isokinetic knee muscle strength. RESULTS: The adjusted mean difference in change in the OARSI sum score was 0.39 (95% CI -0.19 to 0.97), with more progression in the APM group. The incidence of radiographic knee OA was 23% in the APM group and 20% in the exercise group (adjusted risk difference 3% (95% CI -13% to 19%)). No clinically relevant differences were found in patient-reported outcomes or isokinetic knee muscle strength. CONCLUSION: No differences in radiographic knee OA progression and comparable rates of knee OA development were observed 10 years following APM and exercise therapy for degenerative meniscal tears. Both treatments were associated with improved patient-reported pain and knee function. TRIAL REGISTRATION NUMBER: NCT01002794.

@article{sillanpaa_effect_2025,
	title = {Effect of arthroscopic partial meniscectomy on structural degeneration of the knee - {A} 5-year {MRI}-based follow-up of the placebo-surgery controlled {FIDELITY} ({Finnish} {Degenerative} {Meniscus} {Lesion} {Study}) trial},
	volume = {33},
	issn = {1522-9653},
	doi = {10.1016/j.joca.2024.09.003},
	abstract = {OBJECTIVE: To assess the 5-year effects of arthroscopic partial meniscectomy (APM) vs. placebo surgery on the development of the structural changes of the knee by magnetic resonance imaging (MRI).
DESIGN: This multicentre, randomized, participant- and outcome-assessor-blinded, placebo-surgery-controlled trial was carried out in Finland. We randomized 146 adults, mean age 52 years (range 35 to 65) to undergo either APM or placebo surgery. The subjects had symptoms of degenerative medial meniscus tear, a tear verified in MRI and arthroscopy, and no advanced osteoarthritis at baseline. We compared the baseline and 5-year follow-up MRIs using MRI Osteoarthritis Knee Score scoring to derive subregional data on cartilage damage, osteophytes and bone marrow lesions (BMLs). Progression of structural cartilage changes analyzed per subregion was the main outcome, that of osteophytes and BMLs secondary outcomes. We analyzed the progression with multilevel logistic regression model on subregion-level data, adjusted for randomization stratification factors, and using robust standard errors.
RESULTS: Sixty-three (90\%) subjects in the APM and 73 (96\%) in the placebo-surgery group had MRI at both time points. The adjusted odds ratio (APM vs. placebo-surgery) was 1.31 (95\% confidence interval 0.81, 1.94) for progression of cartilage damage, 2.86 (1.16, 6.21) for osteophytes, and 1.43 (0.84, 2.43) for BMLs.
CONCLUSIONS: We found a slightly greater risk for progression of osteophytes in the APM group compared to the placebo-surgery group at 5 years after surgery.
TRIAL REGISTRATION: ClinicalTrials.gov (NCT01052233 and NCT00549172).},
	language = {eng},
	number = {2},
	journal = {Osteoarthritis and Cartilage},
	author = {Sillanpää, Niko and Iivanainen, Marika and Turkiewicz, Aleksandra and Sihvonen, Raine and Paavola, Mika and Taimela, Simo and Järvinen, Teppo L. N. and Englund, Martin},
	month = feb,
	year = {2025},
	keywords = {Adult, Aged, Arthroscopy, Cartilage, Articular, Disease Progression, Female, Finland, Follow-Up Studies, Humans, Knee, Knee Joint, Knee arthroscopy, Magnetic Resonance Imaging, Magnetic resonance imaging, Male, Meniscectomy, Menisci, Tibial, Meniscus, Middle Aged, Osteoarthritis, Osteoarthritis, Knee, Osteophyte, Placebo surgery, Tibial Meniscus Injuries, Treatment Outcome},
	pages = {276--282},
}

OBJECTIVE: To assess the 5-year effects of arthroscopic partial meniscectomy (APM) vs. placebo surgery on the development of the structural changes of the knee by magnetic resonance imaging (MRI). DESIGN: This multicentre, randomized, participant- and outcome-assessor-blinded, placebo-surgery-controlled trial was carried out in Finland. We randomized 146 adults, mean age 52 years (range 35 to 65) to undergo either APM or placebo surgery. The subjects had symptoms of degenerative medial meniscus tear, a tear verified in MRI and arthroscopy, and no advanced osteoarthritis at baseline. We compared the baseline and 5-year follow-up MRIs using MRI Osteoarthritis Knee Score scoring to derive subregional data on cartilage damage, osteophytes and bone marrow lesions (BMLs). Progression of structural cartilage changes analyzed per subregion was the main outcome, that of osteophytes and BMLs secondary outcomes. We analyzed the progression with multilevel logistic regression model on subregion-level data, adjusted for randomization stratification factors, and using robust standard errors. RESULTS: Sixty-three (90%) subjects in the APM and 73 (96%) in the placebo-surgery group had MRI at both time points. The adjusted odds ratio (APM vs. placebo-surgery) was 1.31 (95% confidence interval 0.81, 1.94) for progression of cartilage damage, 2.86 (1.16, 6.21) for osteophytes, and 1.43 (0.84, 2.43) for BMLs. CONCLUSIONS: We found a slightly greater risk for progression of osteophytes in the APM group compared to the placebo-surgery group at 5 years after surgery. TRIAL REGISTRATION: ClinicalTrials.gov (NCT01052233 and NCT00549172).

@article{cronstrom_symptoms_2025,
	title = {Symptoms indicative of early knee osteoarthritis after {ACL} reconstruction: descriptive analysis of the {SHIELD} cohort},
	volume = {7},
	issn = {2665-9131},
	shorttitle = {Symptoms indicative of early knee osteoarthritis after {ACL} reconstruction},
	doi = {10.1016/j.ocarto.2025.100576},
	abstract = {OBJECTIVE: To describe the SHIELD cohort in terms of symptoms indicative of early knee osteoarthritis (OA) and to investigate associations between patient characteristics (demographics, activity/injury-related) and these symptoms at 1 (cross-sectional) and 3 years (longitudinal) post anterior cruciate ligament reconstruction (ACLR).
METHOD: 106 participants (50 ​\% women, mean [SD] age 25 [5] years) were included. Symptoms indicative of early knee OA were evaluated by the Knee injury and Osteoarthritis Outcome Score (KOOS) subscale pain, KOOS subscale pain ≤72 (KOOSpain ≤72), and ≤85 on two out of four KOOS subscales (pain, symptoms, activity of daily living, quality of life) (modified Luyten).
RESULTS: Mean (SD) KOOS pain scores were 83.2 (15.7) and 87.3 (12.7) at 1 and 3 years, respectively. At 1 year and 3 years post ACLR, 18/101 (18 ​\%) and 14/86 (16 ​\%) participants met the KOOSpain ≤72 criterion, whereas 83/101 (82 ​\%) and 67/86 (78 ​\%) met the modified Luyten criterion. 7/15 (47 ​\%) (KOOSpain ≤72) and 59/70 (84 ​\%) (modified Luyten) classified as having knee OA symptoms 1 year post ACLR were still classified as having OA symptoms after 3 years. Lower activity level at 1 year was the sole variable consistently associated with all three outcomes 3 years post ACLR.
CONCLUSION: The proportion of participants fulfilling existing classification criteria for symptoms indicative of early OA after ACLR is highly dependent on the criteria applied and different criteria seem to capture varying aspects of early OA symptoms. Future studies will reveal if these symptoms will persist long-term or just reflect more transient issues.},
	language = {eng},
	number = {1},
	journal = {Osteoarthritis and Cartilage Open},
	author = {Cronström, Anna and Risberg, May Arna and Englund, Martin and Strauss, Dorthe B. and Neuman, Paul and Tiderius, Carl Johan and Ageberg, Eva},
	month = mar,
	year = {2025},
	keywords = {Classification criteria, Knee injury, Patient characteristics},
	pages = {100576},
}

OBJECTIVE: To describe the SHIELD cohort in terms of symptoms indicative of early knee osteoarthritis (OA) and to investigate associations between patient characteristics (demographics, activity/injury-related) and these symptoms at 1 (cross-sectional) and 3 years (longitudinal) post anterior cruciate ligament reconstruction (ACLR). METHOD: 106 participants (50 ​% women, mean [SD] age 25 [5] years) were included. Symptoms indicative of early knee OA were evaluated by the Knee injury and Osteoarthritis Outcome Score (KOOS) subscale pain, KOOS subscale pain ≤72 (KOOSpain ≤72), and ≤85 on two out of four KOOS subscales (pain, symptoms, activity of daily living, quality of life) (modified Luyten). RESULTS: Mean (SD) KOOS pain scores were 83.2 (15.7) and 87.3 (12.7) at 1 and 3 years, respectively. At 1 year and 3 years post ACLR, 18/101 (18 ​%) and 14/86 (16 ​%) participants met the KOOSpain ≤72 criterion, whereas 83/101 (82 ​%) and 67/86 (78 ​%) met the modified Luyten criterion. 7/15 (47 ​%) (KOOSpain ≤72) and 59/70 (84 ​%) (modified Luyten) classified as having knee OA symptoms 1 year post ACLR were still classified as having OA symptoms after 3 years. Lower activity level at 1 year was the sole variable consistently associated with all three outcomes 3 years post ACLR. CONCLUSION: The proportion of participants fulfilling existing classification criteria for symptoms indicative of early OA after ACLR is highly dependent on the criteria applied and different criteria seem to capture varying aspects of early OA symptoms. Future studies will reveal if these symptoms will persist long-term or just reflect more transient issues.

@article{englund_regression_2025,
	title = {Regression to the mean for physical function and quality of life in clinical trials for symptomatic knee osteoarthritis},
	volume = {33},
	issn = {1522-9653},
	doi = {10.1016/j.joca.2024.11.006},
	abstract = {OBJECTIVE: To estimate the size of regression to the mean (RTM) for common patient-reported outcomes in trials for knee osteoarthritis (OA).
DESIGN: Longitudinal cohort study; we included participants of the Osteoarthritis Initiative who fulfilled typical inclusion criteria for enrolment in a trial. These included: age 40-79 years, symptomatic knee OA, Kellgren-Lawrence grade 2-3, use of pain medication more than half the days of a month in past 12 months, numerical rating scale pain of 4 to 9. We studied observed changes in WOMAC physical function and KOOS quality of life (QOL).
RESULTS: We identified 547 subjects who fulfilled inclusion criteria on at least one annual follow-up between year 1 and year 8. The mean level of physical function and QOL at each follow-up time point was similar, about 18 and about 51, respectively. However, at the time of theoretical inclusion in a trial, the mean levels in the same subjects were 23 and 43, respectively (both worse scores). The mean improvement in physical function between inclusion and 1 and 2 years later, respectively, was 2.5 (95\% confidence interval 1.7 to 3.2) and 3.1 (2.3 to 3.8). The corresponding improvement in QOL was 2.7 (1.7 to 3.7) and 4.2 (3.1 to 5.3).
CONCLUSION: RTM in trials for knee OA is likely to explain improvement in physical function and QOL, not only in knee pain. RTM often misleads investigators to overinterpret effectiveness as RTM neither represents improvement from the intervention nor placebo effect from the intervention and its context.},
	language = {eng},
	number = {3},
	journal = {Osteoarthritis and Cartilage},
	author = {Englund, Martin and Turkiewicz, Aleksandra},
	month = mar,
	year = {2025},
	keywords = {Adult, Aged, Clinical Trial, Female, Function, Humans, Longitudinal Studies, Male, Middle Aged, Osteoarthritis, Osteoarthritis, Knee, Pain Measurement, Patient Reported Outcome Measures, Quality of Life, Quality of life, Treatment Efficacy},
	pages = {391--395},
}

OBJECTIVE: To estimate the size of regression to the mean (RTM) for common patient-reported outcomes in trials for knee osteoarthritis (OA). DESIGN: Longitudinal cohort study; we included participants of the Osteoarthritis Initiative who fulfilled typical inclusion criteria for enrolment in a trial. These included: age 40-79 years, symptomatic knee OA, Kellgren-Lawrence grade 2-3, use of pain medication more than half the days of a month in past 12 months, numerical rating scale pain of 4 to 9. We studied observed changes in WOMAC physical function and KOOS quality of life (QOL). RESULTS: We identified 547 subjects who fulfilled inclusion criteria on at least one annual follow-up between year 1 and year 8. The mean level of physical function and QOL at each follow-up time point was similar, about 18 and about 51, respectively. However, at the time of theoretical inclusion in a trial, the mean levels in the same subjects were 23 and 43, respectively (both worse scores). The mean improvement in physical function between inclusion and 1 and 2 years later, respectively, was 2.5 (95% confidence interval 1.7 to 3.2) and 3.1 (2.3 to 3.8). The corresponding improvement in QOL was 2.7 (1.7 to 3.7) and 4.2 (3.1 to 5.3). CONCLUSION: RTM in trials for knee OA is likely to explain improvement in physical function and QOL, not only in knee pain. RTM often misleads investigators to overinterpret effectiveness as RTM neither represents improvement from the intervention nor placebo effect from the intervention and its context.

@article{lawford_change_2025,
	title = {Change in willingness for surgery and risk of joint replacement after an education and exercise program for hip/knee osteoarthritis: {A} longitudinal cohort study of 55,059 people},
	volume = {22},
	issn = {1549-1676},
	shorttitle = {Change in willingness for surgery and risk of joint replacement after an education and exercise program for hip/knee osteoarthritis},
	doi = {10.1371/journal.pmed.1004577},
	abstract = {BACKGROUND: Numerous studies report that education and exercise interventions can shift people's willingness to undergo joint replacement surgery for osteoarthritis. We aimed to investigate whether becoming unwilling to undergo surgery following an education and exercise intervention for hip and knee osteoarthritis is associated with lower probability of receiving actual surgery.
METHODS AND FINDINGS: This was a register-based cohort study including people from the Swedish Osteoarthritis Register who underwent a 3-month education and exercise intervention for knee or hip osteoarthritis. Participants self-reported their willingness to have joint replacement surgery ('yes' or 'no') and were grouped based on their response pre- and post-intervention (always willing for surgery; became unwilling for surgery; never willing for surgery; became willing for surgery). Data on joint replacement surgery was obtained through the Swedish Arthroplasty Register. The probability and hazard of surgery occurring, as well as the mean time without surgery was calculated up to 5-years (primary outcome) and 9-years (secondary outcome) post-intervention. We adjusted for age, sex, body mass index (BMI), education, joint pain, quality of life, walking difficulties, number of prior visits with an orthopedic surgeon, prior joint surgeries in the knee or hip (other than joint replacement), and comorbidities. 55,059 people were included, 69\% were female (N = 37,739), with a mean age 66years (standard deviation [SD] = 9.3), and a BMI of 27.5 (SD = 4.9). In total, 70\% (N = 38,386) were never willing for surgery, 14\% (N = 7,736) were always willing for surgery, 10\% (N = 5,649) became unwilling for surgery, and 6\% (N = 3,288) became willing for surgery. Compared to those who were always willing for surgery, participants who became unwilling had a 20\% (95\% confidence interval [CI]: 18, 22\%) lower probability of having surgery by 5-years post-intervention. This corresponded to delaying surgery by 1.1 (95\% CI: 1.0, 1.1) years. Compared to those who were always willing for surgery, the hazard of surgery occurring at 1-year post-intervention was lower in those who became unwilling (hazard ratio (HR) 0.5 [95\% CI: 0.4, 0.5]), though was then higher at 5-years (HR 1.4 [95\% CI: 1.2, 1.7]). Estimates remained stable from 5 to 9 years. Limitations of our study include the inability to account for all potential confounders, and to infer the contribution of the intervention to change in willingness for surgery due to the absence of a control group. Data were collected in Sweden, generalisability to other countries may be limited.
CONCLUSIONS: Becoming unwilling for joint replacement surgery following an education and exercise program for hip and knee osteoarthritis could reduce the number of joint replacement surgeries by 20\% at 5 years post-intervention, with the possibility of maintaining most of this reduction up to 9 years post-intervention. Interventions that can shift willingness to undergo surgery may thus result in relevant delays and reductions in future joint replacements.},
	language = {eng},
	number = {5},
	journal = {PLoS medicine},
	author = {Lawford, Belinda J. and Kiadaliri, Ali and Englund, Martin and Bennell, Kim L. and Hinman, Rana S. and Hall, Michelle and Dell'Isola, Andrea},
	month = may,
	year = {2025},
	keywords = {Aged, Arthroplasty, Replacement, Hip, Arthroplasty, Replacement, Knee, Cohort Studies, Exercise, Exercise Therapy, Female, Humans, Longitudinal Studies, Male, Middle Aged, Osteoarthritis, Hip, Osteoarthritis, Knee, Patient Education as Topic, Registries, Sweden},
	pages = {e1004577},
}

BACKGROUND: Numerous studies report that education and exercise interventions can shift people's willingness to undergo joint replacement surgery for osteoarthritis. We aimed to investigate whether becoming unwilling to undergo surgery following an education and exercise intervention for hip and knee osteoarthritis is associated with lower probability of receiving actual surgery. METHODS AND FINDINGS: This was a register-based cohort study including people from the Swedish Osteoarthritis Register who underwent a 3-month education and exercise intervention for knee or hip osteoarthritis. Participants self-reported their willingness to have joint replacement surgery ('yes' or 'no') and were grouped based on their response pre- and post-intervention (always willing for surgery; became unwilling for surgery; never willing for surgery; became willing for surgery). Data on joint replacement surgery was obtained through the Swedish Arthroplasty Register. The probability and hazard of surgery occurring, as well as the mean time without surgery was calculated up to 5-years (primary outcome) and 9-years (secondary outcome) post-intervention. We adjusted for age, sex, body mass index (BMI), education, joint pain, quality of life, walking difficulties, number of prior visits with an orthopedic surgeon, prior joint surgeries in the knee or hip (other than joint replacement), and comorbidities. 55,059 people were included, 69% were female (N = 37,739), with a mean age 66years (standard deviation [SD] = 9.3), and a BMI of 27.5 (SD = 4.9). In total, 70% (N = 38,386) were never willing for surgery, 14% (N = 7,736) were always willing for surgery, 10% (N = 5,649) became unwilling for surgery, and 6% (N = 3,288) became willing for surgery. Compared to those who were always willing for surgery, participants who became unwilling had a 20% (95% confidence interval [CI]: 18, 22%) lower probability of having surgery by 5-years post-intervention. This corresponded to delaying surgery by 1.1 (95% CI: 1.0, 1.1) years. Compared to those who were always willing for surgery, the hazard of surgery occurring at 1-year post-intervention was lower in those who became unwilling (hazard ratio (HR) 0.5 [95% CI: 0.4, 0.5]), though was then higher at 5-years (HR 1.4 [95% CI: 1.2, 1.7]). Estimates remained stable from 5 to 9 years. Limitations of our study include the inability to account for all potential confounders, and to infer the contribution of the intervention to change in willingness for surgery due to the absence of a control group. Data were collected in Sweden, generalisability to other countries may be limited. CONCLUSIONS: Becoming unwilling for joint replacement surgery following an education and exercise program for hip and knee osteoarthritis could reduce the number of joint replacement surgeries by 20% at 5 years post-intervention, with the possibility of maintaining most of this reduction up to 9 years post-intervention. Interventions that can shift willingness to undergo surgery may thus result in relevant delays and reductions in future joint replacements.

@article{filbay_association_2025,
	title = {Association {Between} {ACL} {Continuity} on {Magnetic} {Resonance} {Imaging} at 5 {Years} {After} an {Acute} {ACL} {Rupture} and 11-{Year} {Outcomes}: {A} {Secondary} {Analysis} {From} the {KANON} {Trial}},
	volume = {53},
	issn = {1552-3365},
	shorttitle = {Association {Between} {ACL} {Continuity} on {Magnetic} {Resonance} {Imaging} at 5 {Years} {After} an {Acute} {ACL} {Rupture} and 11-{Year} {Outcomes}},
	doi = {10.1177/03635465251339061},
	abstract = {BACKGROUND: Emerging evidence suggests that anterior cruciate ligament (ACL) ruptures can restore ACL fiber continuity. The relationship between ACL continuity on magnetic resonance imaging (MRI) (sign of ACL healing) and outcomes {\textgreater}5 years after an acute ACL rupture has not been investigated.
PURPOSE: This study aimed to (1) describe clinical outcomes and radiographic osteoarthritis (ROA) at 11 years based on ACL continuity status at 5 years and (2) investigate the relationship between 5-year ACL continuity status and 11-year Knee Injury and Osteoarthritis Outcome Score (KOOS4) scores.
STUDY DESIGN: Secondary analysis of KANON randomized controlled trial; Level of evidence, 3.
METHODS: Overall, 105 of 121 (87\%) active adults with acute ACL ruptures randomized to undergo initial exercise therapy and optional delayed ACL reconstruction (ACLR) or early ACLR and postoperative exercise therapy completed 11-year follow-up. MRI scans at 5 years were evaluated using the Anterior Cruciate Ligament OsteoArthritis Score (0-3), with grades 0 to 2 considered to represent "ACL continuity." Patient-reported outcomes (KOOS4, 36-Item Short Form Health Survey, Tegner Activity Scale, self-reported new knee injuries), knee laxity, and radiographic findings (tibiofemoral and/or patellofemoral ROA) were assessed at 11 years. The relationship between 5-year ACL continuity and 11-year KOOS4 scores (0-100) was examined using linear regression, adjusted for age, sex, smoking, and baseline KOOS4 scores.
RESULTS: Of patients managed nonsurgically, 58\% (n = 14) had ACL continuity and 42\% (n = 10) had ACL discontinuity at 5 years. Analyses suggest that ACL continuity was associated with worse 11-year KOOS4 scores compared with delayed ACLR (adjusted mean difference, -20.2 [95\% CI, -31.9 to -8.6]) and early ACLR (adjusted mean difference, -15.5 [95\% CI, -26.4 to -4.7]) as well as similar or worse KOOS4 scores compared with ACL discontinuity (adjusted mean difference, -11.4 [95\% CI, -26.5 to 3.6]). The proportion of patients with tibiofemoral ROA ranged from 14\% (ACL continuity) to 23\% (delayed ACLR), and the proportion of patients with patellofemoral ROA ranged from 11\% (ACL discontinuity) to 41\% (early ACLR).
CONCLUSION: ACL continuity on 5-year MRI may be associated with worse patient-reported outcomes at 11 years after an ACL injury compared with early or delayed ACLR.
REGISTRATION: 84752559 (ISRCTN).},
	language = {eng},
	number = {8},
	journal = {The American Journal of Sports Medicine},
	author = {Filbay, Stephanie R. and Roemer, Frank and Roos, Ewa M. and Turkiewicz, Aleksandra and Frobell, Richard and Lohmander, L. Stefan and Englund, Martin},
	month = jul,
	year = {2025},
	keywords = {Adult, Anterior Cruciate Ligament, Anterior Cruciate Ligament Injuries, Anterior Cruciate Ligament Reconstruction, Exercise Therapy, Female, Follow-Up Studies, Humans, Magnetic Resonance Imaging, Male, Osteoarthritis, Knee, Patient Reported Outcome Measures, Rupture, Treatment Outcome, Young Adult, anterior cruciate ligament reconstruction, magnetic resonance imaging, osteoarthritis, rehabilitation},
	pages = {1893--1900},
}

BACKGROUND: Emerging evidence suggests that anterior cruciate ligament (ACL) ruptures can restore ACL fiber continuity. The relationship between ACL continuity on magnetic resonance imaging (MRI) (sign of ACL healing) and outcomes \textgreater5 years after an acute ACL rupture has not been investigated. PURPOSE: This study aimed to (1) describe clinical outcomes and radiographic osteoarthritis (ROA) at 11 years based on ACL continuity status at 5 years and (2) investigate the relationship between 5-year ACL continuity status and 11-year Knee Injury and Osteoarthritis Outcome Score (KOOS4) scores. STUDY DESIGN: Secondary analysis of KANON randomized controlled trial; Level of evidence, 3. METHODS: Overall, 105 of 121 (87%) active adults with acute ACL ruptures randomized to undergo initial exercise therapy and optional delayed ACL reconstruction (ACLR) or early ACLR and postoperative exercise therapy completed 11-year follow-up. MRI scans at 5 years were evaluated using the Anterior Cruciate Ligament OsteoArthritis Score (0-3), with grades 0 to 2 considered to represent "ACL continuity." Patient-reported outcomes (KOOS4, 36-Item Short Form Health Survey, Tegner Activity Scale, self-reported new knee injuries), knee laxity, and radiographic findings (tibiofemoral and/or patellofemoral ROA) were assessed at 11 years. The relationship between 5-year ACL continuity and 11-year KOOS4 scores (0-100) was examined using linear regression, adjusted for age, sex, smoking, and baseline KOOS4 scores. RESULTS: Of patients managed nonsurgically, 58% (n = 14) had ACL continuity and 42% (n = 10) had ACL discontinuity at 5 years. Analyses suggest that ACL continuity was associated with worse 11-year KOOS4 scores compared with delayed ACLR (adjusted mean difference, -20.2 [95% CI, -31.9 to -8.6]) and early ACLR (adjusted mean difference, -15.5 [95% CI, -26.4 to -4.7]) as well as similar or worse KOOS4 scores compared with ACL discontinuity (adjusted mean difference, -11.4 [95% CI, -26.5 to 3.6]). The proportion of patients with tibiofemoral ROA ranged from 14% (ACL continuity) to 23% (delayed ACLR), and the proportion of patients with patellofemoral ROA ranged from 11% (ACL discontinuity) to 41% (early ACLR). CONCLUSION: ACL continuity on 5-year MRI may be associated with worse patient-reported outcomes at 11 years after an ACL injury compared with early or delayed ACLR. REGISTRATION: 84752559 (ISRCTN).

@article{boric-persson_increased_2025,
	title = {Increased reoperation rates after meniscus repair compared to arthroscopic partial meniscectomy: {Data} from a comprehensive clinical cohort with up to 10 years follow-up},
	issn = {1433-7347},
	shorttitle = {Increased reoperation rates after meniscus repair compared to arthroscopic partial meniscectomy},
	doi = {10.1002/ksa.12791},
	abstract = {PURPOSE: To investigate the rates of knee reoperation and medical complications after meniscal repair versus partial meniscectomy (APM) up to 10 years after surgery.
METHODS: All patients ≥ 15 years old operated for a meniscal tear with meniscus repair or partial meniscectomy at Scania University Hospital were included, between year 2010 and 2014. Information was retrieved from patient records until the year 2020. Rates of any reoperation, reoperation in same meniscus and medical complications were estimated. Differences were also estimated in the three outcomes in a subgroup aged 15-40 years using flexible parametric survival models adjusted for age, sex, knee laterality, tear type, medial/lateral, anterior cruciate ligament (ACL) status, osteoarthritis, body mass, height and smoking.
RESULTS: Records identified 2098 patients (395 undergoing meniscal repair and 1703 partial meniscectomy) with 540 reoperations in 430 patients. The incidence rate of reoperation was 32/1000 person-years (95\% confidence interval [CI] 29-35) and of reoperation in the same meniscus 19/1000 person-years (95\% CI 17-21). There were 2.1\% postoperative complications. In the age group 15-40 years, with only bucket-handle, longitudinal and horizontal tears, 341 patients had meniscal repair and 361 partial meniscectomy. The incidence rate of any reoperation was 105 (95\% CI 90-122) per 1000 person-years in the meniscal repair group and 24 (95\% CI 18-31) in the partial meniscectomy group. The adjusted hazard ratio of any reoperation comparing meniscal repair with partial meniscectomy was 4.3 (95\% CI 3.1-6.0) and of reoperations in the same meniscus 17 (95\% CI 9-31). 3.3\% patients had postoperative complications (15 after meniscal repair and 14 after partial meniscectomy).
CONCLUSIONS: The risk of any knee reoperation after meniscal repair had a four-fold increase compared with partial meniscectomy, and for same meniscus reoperations about 17-fold. The rate of medical postoperative complications was low.
LEVEL OF EVIDENCE: Level III.},
	language = {eng},
	journal = {Knee surgery, sports traumatology, arthroscopy: official journal of the ESSKA},
	author = {Boric-Persson, Fredrik and Turkiewicz, Aleksandra and Englund, Martin and Neuman, Paul},
	month = jul,
	year = {2025},
	keywords = {arthroscopy, knee surgery, meniscectomy, meniscus repair, reoperation},
}

PURPOSE: To investigate the rates of knee reoperation and medical complications after meniscal repair versus partial meniscectomy (APM) up to 10 years after surgery. METHODS: All patients ≥ 15 years old operated for a meniscal tear with meniscus repair or partial meniscectomy at Scania University Hospital were included, between year 2010 and 2014. Information was retrieved from patient records until the year 2020. Rates of any reoperation, reoperation in same meniscus and medical complications were estimated. Differences were also estimated in the three outcomes in a subgroup aged 15-40 years using flexible parametric survival models adjusted for age, sex, knee laterality, tear type, medial/lateral, anterior cruciate ligament (ACL) status, osteoarthritis, body mass, height and smoking. RESULTS: Records identified 2098 patients (395 undergoing meniscal repair and 1703 partial meniscectomy) with 540 reoperations in 430 patients. The incidence rate of reoperation was 32/1000 person-years (95% confidence interval [CI] 29-35) and of reoperation in the same meniscus 19/1000 person-years (95% CI 17-21). There were 2.1% postoperative complications. In the age group 15-40 years, with only bucket-handle, longitudinal and horizontal tears, 341 patients had meniscal repair and 361 partial meniscectomy. The incidence rate of any reoperation was 105 (95% CI 90-122) per 1000 person-years in the meniscal repair group and 24 (95% CI 18-31) in the partial meniscectomy group. The adjusted hazard ratio of any reoperation comparing meniscal repair with partial meniscectomy was 4.3 (95% CI 3.1-6.0) and of reoperations in the same meniscus 17 (95% CI 9-31). 3.3% patients had postoperative complications (15 after meniscal repair and 14 after partial meniscectomy). CONCLUSIONS: The risk of any knee reoperation after meniscal repair had a four-fold increase compared with partial meniscectomy, and for same meniscus reoperations about 17-fold. The rate of medical postoperative complications was low. LEVEL OF EVIDENCE: Level III.

@article{sall_addressing_2025,
	title = {Addressing fatty tissue in quantitative susceptibility mapping of human knee cartilage},
	issn = {1352-8661},
	doi = {10.1007/s10334-025-01280-0},
	abstract = {OBJECTIVE: To evaluate the effects of excluding fatty tissue in QSM of human knee cartilage.
MATERIALS AND METHODS: Gradient echo images from 18 knee-healthy volunteers were acquired, from which chemical shift corrected field perturbation maps were calculated. Based on these, QSM maps were reconstructed using morphology enabled dipole inversion and one of three masking alternatives: (1) excluding no tissue, (2) excluding bone marrow, and (3) excluding all fatty tissues. The slope of a linear regression [ppm/\%] between susceptibility values and the relative distance from the bone surfaces was used as a measurement of contrast between cartilage layers. The average differences in slopes between methods are reported with 95\% confidence intervals.
RESULTS: The expected susceptibility differences between cartilage layers from literature were observed for all tested reconstruction techniques. However, smaller slopes (average difference (confidence interval)) were detected when either all fatty tissue (- 0.090 (- 0.121, - 0.059) ppm/\%) or bone marrow (- 0.088 (- 0.121, - 0.055) ppm/\%) was excluded from reconstruction.
DISCUSSION: All tested methods result in adequate image quality in QSM of knee cartilage. However, exclusion of fatty tissue decreased the susceptibility contrast between cartilage layers. Assuming that phase contributions from chemical shift are addressed, inclusion of fatty tissue may be preferable.},
	language = {eng},
	journal = {Magma (New York, N.Y.)},
	author = {Säll, Cornelia and Lind, Emelie and Einarsson, Emma and Turkiewicz, Aleksandra and Englund, Martin and Peterson, Pernilla},
	month = jul,
	year = {2025},
	keywords = {Cartilage, Fatty tissue, Osteoarthritis, QSM},
}

OBJECTIVE: To evaluate the effects of excluding fatty tissue in QSM of human knee cartilage. MATERIALS AND METHODS: Gradient echo images from 18 knee-healthy volunteers were acquired, from which chemical shift corrected field perturbation maps were calculated. Based on these, QSM maps were reconstructed using morphology enabled dipole inversion and one of three masking alternatives: (1) excluding no tissue, (2) excluding bone marrow, and (3) excluding all fatty tissues. The slope of a linear regression [ppm/%] between susceptibility values and the relative distance from the bone surfaces was used as a measurement of contrast between cartilage layers. The average differences in slopes between methods are reported with 95% confidence intervals. RESULTS: The expected susceptibility differences between cartilage layers from literature were observed for all tested reconstruction techniques. However, smaller slopes (average difference (confidence interval)) were detected when either all fatty tissue (- 0.090 (- 0.121, - 0.059) ppm/%) or bone marrow (- 0.088 (- 0.121, - 0.055) ppm/%) was excluded from reconstruction. DISCUSSION: All tested methods result in adequate image quality in QSM of knee cartilage. However, exclusion of fatty tissue decreased the susceptibility contrast between cartilage layers. Assuming that phase contributions from chemical shift are addressed, inclusion of fatty tissue may be preferable.

@article{tajik_association_2025,
	title = {Association between injury-related factors and cartilage {T2} relaxation time in the subacute phase in patients after anterior cruciate ligament injury},
	volume = {33},
	issn = {1522-9653},
	doi = {10.1016/j.joca.2025.05.002},
	abstract = {OBJECTIVE: To investigate associations between meniscal tear, bone marrow lesions (BMLs), and post-injury knee loading, with cartilage T2 relaxation times on knee magnetic resonance imaging (MRI) in the subacute phase following acute anterior cruciate ligament (ACL) injury.
DESIGN: We studied both knees of 128 patients with ACL injury. The presence of meniscal tears and BMLs was determined on subacute MRI (mean 29 days [SD 13] post injury), and post-injury knee loading was measured using an accelerometer. Manual cartilage segmentation and T2 relaxation time mapping of tibiofemoral cartilage were performed on both knees. We used multiple linear regression models adjusted for age, sex, body mass index, and time from injury to MRI to evaluate the association between exposures and cartilage T2 relaxation times in the ACL-injured knee between individuals. We also performed paired t-tests for comparisons with the individual's non-ACL injured contralateral knee free of the exposure of interest.
RESULTS: There was an association between ipsilateral meniscal tear and prolonged T2 relaxation time in the superficial cartilage of posterior tibia in both compartments (beta-coefficient medial: 2.88, [95\% CI 1.16-4.61], beta-coefficient lateral: 1.88, [0.17-3.58]). Findings were confirmed in the paired analyses with contralateral knees (mean T2 difference 1.43, [0.33-2.53] and 2.10 [0.48-3.71] respectively). We found no essential associations for the other cartilage subregions or for BMLs and knee loading.
CONCLUSION: In the subacute phase after ACL injury, ipsilateral meniscal tear is associated with prolonged cartilage T2 relaxation time in the posterior tibia. This finding highlights the importance of meniscus function in the ACL-injured knee.},
	language = {eng},
	number = {8},
	journal = {Osteoarthritis and Cartilage},
	author = {Tajik, Bashir Edwardsson and Kvist, Joanna and Gauffin, Håkan and Cristiani, Riccardo and Frobell, Richard and Nieminen, Miika and Casula, Victor and Englund, Martin},
	month = aug,
	year = {2025},
	keywords = {Adolescent, Adult, Anterior Cruciate Ligament Injuries, Anterior cruciate ligament, Bone Marrow, Cartilage, Cartilage, Articular, Female, Humans, Knee, Magnetic Resonance Imaging, Magnetic resonance imaging, Male, Menisci, Middle Aged, Tibial, Tibial Meniscus Injuries, Weight-Bearing, Young Adult},
	pages = {1033--1040},
}

OBJECTIVE: To investigate associations between meniscal tear, bone marrow lesions (BMLs), and post-injury knee loading, with cartilage T2 relaxation times on knee magnetic resonance imaging (MRI) in the subacute phase following acute anterior cruciate ligament (ACL) injury. DESIGN: We studied both knees of 128 patients with ACL injury. The presence of meniscal tears and BMLs was determined on subacute MRI (mean 29 days [SD 13] post injury), and post-injury knee loading was measured using an accelerometer. Manual cartilage segmentation and T2 relaxation time mapping of tibiofemoral cartilage were performed on both knees. We used multiple linear regression models adjusted for age, sex, body mass index, and time from injury to MRI to evaluate the association between exposures and cartilage T2 relaxation times in the ACL-injured knee between individuals. We also performed paired t-tests for comparisons with the individual's non-ACL injured contralateral knee free of the exposure of interest. RESULTS: There was an association between ipsilateral meniscal tear and prolonged T2 relaxation time in the superficial cartilage of posterior tibia in both compartments (beta-coefficient medial: 2.88, [95% CI 1.16-4.61], beta-coefficient lateral: 1.88, [0.17-3.58]). Findings were confirmed in the paired analyses with contralateral knees (mean T2 difference 1.43, [0.33-2.53] and 2.10 [0.48-3.71] respectively). We found no essential associations for the other cartilage subregions or for BMLs and knee loading. CONCLUSION: In the subacute phase after ACL injury, ipsilateral meniscal tear is associated with prolonged cartilage T2 relaxation time in the posterior tibia. This finding highlights the importance of meniscus function in the ACL-injured knee.

@article{xie_postoperative_2025,
	title = {Postoperative {Weight} {Loss} {After} {Antiobesity} {Medications} and {Revision} {Risk} {After} {Joint} {Replacement}},
	volume = {8},
	issn = {2574-3805},
	doi = {10.1001/jamanetworkopen.2024.61200},
	abstract = {IMPORTANCE: The 2023 American College of Rheumatology and American Association of Hip and Knee Surgeons Clinical Practice Guideline concluded that obesity alone should not delay joint replacement. Therefore, a substantially increased utilization of joint replacement among patients with obesity could be expected. However, patients with obesity are at increased risk of revision, posing unique challenges as the surgery is complex and costly, and it remains unknown whether postoperative weight loss could decrease the risk of revision.
OBJECTIVE: To examine the association of the proportion of postoperative weight loss following antiobesity medication use with the risk of revision among patients with obesity undergoing hip or knee replacement.
DESIGN, SETTING, AND PARTICIPANTS: Using a target trial emulation, a causal inference framework, this retrospective cohort study investigated patients with obesity who underwent hip or knee replacement. Data were from the IQVIA Medical Research Database (2000-2023). Statistical analysis was performed from October 2023 to June 2024.
MAIN OUTCOMES AND MEASURES: Emulated analyses of a hypothetical target trial were assessed for the association of small-to-moderate (2\%-10\%) or large (≥10\%) weight loss after initiating antiobesity medications (orlistat, sibutramine, glucagon-like peptide-1 receptor agonists, and rimonabant) within 1 year with the risk of 5-year and 10-year revision after initiation of antiobesity medications.
RESULTS: Among 3691 qualified participants (mean [SD] age, 64.7 [9.3] years; 2322 [62.9\%] women), the 5-year risks of revision were 5.6\%, 4.4\%, and 3.7\% for weight gain or stable, small-to-moderate weight loss, and large weight loss groups, respectively. Compared with the weight gain or stable group, the hazard ratios (HRs) were 0.75 (95\% CI, 0.55-1.04) for the small-to-moderate weight loss group and 0.57 (95\% CI, 0.36-0.91) for the large weight loss group. Similar results were observed when the analyses were performed separately for hip or knee replacement. The HRs for revision were 0.55 (95\% CI, 0.32-0.93) for small-to-moderate weight loss and 0.49 (95\% CI, 0.25-0.97) for large weight loss groups compared with the weight gain or stable group in patients undergoing knee replacement; the corresponding HRs for revision were 0.82 (95\% CI, 0.54-1.25) and 0.53 (95\% CI, 0.30-0.93) in patients undergoing hip replacement. Consistent findings were obtained regarding the association of weight loss with the 10-year risks after initiating antiobesity medications.
CONCLUSIONS AND RELEVANCE: In this cohort study using a target trial emulation, a higher proportion of weight loss after initiating antiobesity medications within 1 year was associated with a lower risk of 5-year and 10-year revision among patients with obesity undergoing joint replacement. These results suggest that antiobesity medication use, with relatively safe and sustainable weight loss, may be an effective strategy for improving implant survivorship of hip and knee replacements in the obese population.},
	language = {eng},
	number = {2},
	journal = {JAMA network open},
	author = {Xie, Dongxing and Englund, Martin and Lane, Nancy E. and Zhang, Yuqing and Li, Xiaoxiao and Wei, Jie and Zeng, Chao and Lei, Guanghua},
	month = feb,
	year = {2025},
	keywords = {Aged, Anti-Obesity Agents, Arthroplasty, Replacement, Hip, Arthroplasty, Replacement, Knee, Female, Humans, Male, Middle Aged, Obesity, Postoperative Period, Reoperation, Retrospective Studies, Weight Loss},
	pages = {e2461200},
}

IMPORTANCE: The 2023 American College of Rheumatology and American Association of Hip and Knee Surgeons Clinical Practice Guideline concluded that obesity alone should not delay joint replacement. Therefore, a substantially increased utilization of joint replacement among patients with obesity could be expected. However, patients with obesity are at increased risk of revision, posing unique challenges as the surgery is complex and costly, and it remains unknown whether postoperative weight loss could decrease the risk of revision. OBJECTIVE: To examine the association of the proportion of postoperative weight loss following antiobesity medication use with the risk of revision among patients with obesity undergoing hip or knee replacement. DESIGN, SETTING, AND PARTICIPANTS: Using a target trial emulation, a causal inference framework, this retrospective cohort study investigated patients with obesity who underwent hip or knee replacement. Data were from the IQVIA Medical Research Database (2000-2023). Statistical analysis was performed from October 2023 to June 2024. MAIN OUTCOMES AND MEASURES: Emulated analyses of a hypothetical target trial were assessed for the association of small-to-moderate (2%-10%) or large (≥10%) weight loss after initiating antiobesity medications (orlistat, sibutramine, glucagon-like peptide-1 receptor agonists, and rimonabant) within 1 year with the risk of 5-year and 10-year revision after initiation of antiobesity medications. RESULTS: Among 3691 qualified participants (mean [SD] age, 64.7 [9.3] years; 2322 [62.9%] women), the 5-year risks of revision were 5.6%, 4.4%, and 3.7% for weight gain or stable, small-to-moderate weight loss, and large weight loss groups, respectively. Compared with the weight gain or stable group, the hazard ratios (HRs) were 0.75 (95% CI, 0.55-1.04) for the small-to-moderate weight loss group and 0.57 (95% CI, 0.36-0.91) for the large weight loss group. Similar results were observed when the analyses were performed separately for hip or knee replacement. The HRs for revision were 0.55 (95% CI, 0.32-0.93) for small-to-moderate weight loss and 0.49 (95% CI, 0.25-0.97) for large weight loss groups compared with the weight gain or stable group in patients undergoing knee replacement; the corresponding HRs for revision were 0.82 (95% CI, 0.54-1.25) and 0.53 (95% CI, 0.30-0.93) in patients undergoing hip replacement. Consistent findings were obtained regarding the association of weight loss with the 10-year risks after initiating antiobesity medications. CONCLUSIONS AND RELEVANCE: In this cohort study using a target trial emulation, a higher proportion of weight loss after initiating antiobesity medications within 1 year was associated with a lower risk of 5-year and 10-year revision among patients with obesity undergoing joint replacement. These results suggest that antiobesity medication use, with relatively safe and sustainable weight loss, may be an effective strategy for improving implant survivorship of hip and knee replacements in the obese population.

@article{battista_impact_2025,
	title = {Impact of an intervention for osteoarthritis based on exercise and education on metabolic health: a register-based study using the {SOAD} cohort},
	volume = {11},
	issn = {2056-5933},
	shorttitle = {Impact of an intervention for osteoarthritis based on exercise and education on metabolic health},
	doi = {10.1136/rmdopen-2024-005133},
	abstract = {OBJECTIVE: This study evaluated the effects of a 6-week osteoarthritis (OA) exercise and education intervention on metabolic health markers, including blood pressure (BP), glycated haemoglobin (HbA1c), high-density lipoprotein (HDL), cholesterol levels and weight in individuals with both OA and diabetes.
METHODS: Data originated from the Swedish Osteoarthritis and Diabetes cohort, which is composed of the Swedish Osteoarthritis Register (SOAR) and National Diabetes Register. We included individuals diagnosed with OA and diabetes who underwent the intervention between January 2008 and December 2019, matched with controls with diabetes who did not based on birth year, sex, OA site (hip/knee) and OA diagnosis year. Outcomes included BP, HbA1c, HDL, total cholesterol levels and weight measured up to 3 years before and after SOAR enrolment. Statistical analyses used two-way fixed-effect models.
RESULTS: The study included 4571 individuals with OA and diabetes (mean age: 69.5, SD: 7.8; women: 52.7\%; knee OA: 71.2\%) and 7925 controls. The intervention group showed a systolic BP decrease of approximately 1.0 mm Hg at 6 and 12 months compared with the control group. HDL levels increased by about 0.02 mmol/L at 12, 18 and 24 months. Weight decreased by approximately 0.5 kg at 6, 18 and 30 months. HbA1c levels increased by approximately 0.5 mmol/mol at 6 months. No essential differences were found in the total cholesterol levels.
CONCLUSION: An OA exercise and education intervention designed following OA clinical practice guidelines led to small and unlikely clinically relevant improvements in metabolic health markers in individuals with OA and diabetes.},
	language = {eng},
	number = {1},
	journal = {RMD open},
	author = {Battista, Simone and Recenti, Filippo and Kiadaliri, Ali and Lohmander, Stefan and Jönsson, Thérése and Abbott, Allan and Vinblad, Johanna and Rolfson, Ola and Englund, Martin and Dell'Isola, Andrea},
	month = feb,
	year = {2025},
	keywords = {Aged, Biomarkers, Blood Pressure, Cohort Studies, Exercise, Exercise Therapy, Female, Glycated Hemoglobin, Health services research, Humans, Male, Middle Aged, Osteoarthritis, Patient Education as Topic, Physical Therapy Modalities, Registries, Sweden},
	pages = {e005133},
}

OBJECTIVE: This study evaluated the effects of a 6-week osteoarthritis (OA) exercise and education intervention on metabolic health markers, including blood pressure (BP), glycated haemoglobin (HbA1c), high-density lipoprotein (HDL), cholesterol levels and weight in individuals with both OA and diabetes. METHODS: Data originated from the Swedish Osteoarthritis and Diabetes cohort, which is composed of the Swedish Osteoarthritis Register (SOAR) and National Diabetes Register. We included individuals diagnosed with OA and diabetes who underwent the intervention between January 2008 and December 2019, matched with controls with diabetes who did not based on birth year, sex, OA site (hip/knee) and OA diagnosis year. Outcomes included BP, HbA1c, HDL, total cholesterol levels and weight measured up to 3 years before and after SOAR enrolment. Statistical analyses used two-way fixed-effect models. RESULTS: The study included 4571 individuals with OA and diabetes (mean age: 69.5, SD: 7.8; women: 52.7%; knee OA: 71.2%) and 7925 controls. The intervention group showed a systolic BP decrease of approximately 1.0 mm Hg at 6 and 12 months compared with the control group. HDL levels increased by about 0.02 mmol/L at 12, 18 and 24 months. Weight decreased by approximately 0.5 kg at 6, 18 and 30 months. HbA1c levels increased by approximately 0.5 mmol/mol at 6 months. No essential differences were found in the total cholesterol levels. CONCLUSION: An OA exercise and education intervention designed following OA clinical practice guidelines led to small and unlikely clinically relevant improvements in metabolic health markers in individuals with OA and diabetes.

@article{king_elucidating_2025,
	title = {Elucidating the initial symptoms and experiences of knee osteoarthritis: {An} international patient survey},
	volume = {33},
	issn = {1522-9653},
	shorttitle = {Elucidating the initial symptoms and experiences of knee osteoarthritis},
	doi = {10.1016/j.joca.2025.05.008},
	abstract = {OBJECTIVES: Within the first phase of developing classification criteria for Early-stage Symptomatic Knee Osteoarthritis, among individuals with knee osteoarthritis (OA) we explored: 1) symptoms within the first year of noticing their knee(s); 2) features that indicated OA was the cause; and 3) timing and reasons that initially prompted seeking healthcare.
DESIGN: We conducted a cross-sectional online survey of individuals with knee OA recruited from Australia, Canada, the Netherlands, and the USA. Only individuals who indicated they recalled their first symptoms were eligible. Using free-text, participants described changes in how their knee looked, felt, moved, their overall state within the first year of noticing their knee(s), features perceived to indicate knee OA was the cause, and reasons for initially seeking healthcare. We assessed the timing of seeking care by an ordinal scale. Data were analyzed using descriptive statistics and summative content analysis.
RESULTS: We included 92 participants (median age 67 years [interquartile range (IQR) 59,75], 69\% women, median body mass index (BMI) 26 kg/m2 [IQR 24,30]). Within the first year from onset, frequently reported symptoms were knee pain (70\%), swelling (58\%), crepitus (42\%), stiffness (29\%), and instability (24\%). While few could provide specific clinical features, approximately half (53\%) perceived medical imaging as important to indicate OA. Only 35\% sought healthcare within the first year of experiencing symptoms.
CONCLUSIONS: Individuals with knee OA recalled varied knee symptoms within the first year and few sought healthcare. We were unable to ascertain, from the perspective of patients, specific clinical features that indicated they had OA and not another condition.},
	language = {eng},
	number = {9},
	journal = {Osteoarthritis and Cartilage},
	author = {King, Lauren K. and Mahmoudian, Armaghan and Liew, Jean W. and Wang, Qiuke and Stanaitis, Ian and Schiphof, Dieuwke and Callahan, Leigh F. and Hunter, David J. and Appleton, C. Thomas and Turkiewicz, Aleksandra and Englund, Martin and Lohmander, L. Stefan and Haugen, Ida K. and Hawker, Gillian A. and Neogi, Tuhina and Runhaar, Jos and {OARSI Early-stage Symptomatic Knee Osteoarthritis Initiative}},
	month = sep,
	year = {2025},
	keywords = {Knee osteoarthritis, Patient-orientated research, Survey, Symptoms},
	pages = {1147--1152},
}

OBJECTIVES: Within the first phase of developing classification criteria for Early-stage Symptomatic Knee Osteoarthritis, among individuals with knee osteoarthritis (OA) we explored: 1) symptoms within the first year of noticing their knee(s); 2) features that indicated OA was the cause; and 3) timing and reasons that initially prompted seeking healthcare. DESIGN: We conducted a cross-sectional online survey of individuals with knee OA recruited from Australia, Canada, the Netherlands, and the USA. Only individuals who indicated they recalled their first symptoms were eligible. Using free-text, participants described changes in how their knee looked, felt, moved, their overall state within the first year of noticing their knee(s), features perceived to indicate knee OA was the cause, and reasons for initially seeking healthcare. We assessed the timing of seeking care by an ordinal scale. Data were analyzed using descriptive statistics and summative content analysis. RESULTS: We included 92 participants (median age 67 years [interquartile range (IQR) 59,75], 69% women, median body mass index (BMI) 26 kg/m2 [IQR 24,30]). Within the first year from onset, frequently reported symptoms were knee pain (70%), swelling (58%), crepitus (42%), stiffness (29%), and instability (24%). While few could provide specific clinical features, approximately half (53%) perceived medical imaging as important to indicate OA. Only 35% sought healthcare within the first year of experiencing symptoms. CONCLUSIONS: Individuals with knee OA recalled varied knee symptoms within the first year and few sought healthcare. We were unable to ascertain, from the perspective of patients, specific clinical features that indicated they had OA and not another condition.

@article{hawker_oarsi_2025,
	title = {{OARSI} initiative to develop classification criteria for early-stage symptomatic knee {OA} ({EsSKOA}): {What} conditions should be considered in the differential diagnosis of {EsSKOA}?},
	volume = {33},
	issn = {1522-9653},
	shorttitle = {{OARSI} initiative to develop classification criteria for early-stage symptomatic knee {OA} ({EsSKOA})},
	doi = {10.1016/j.joca.2025.05.005},
	abstract = {OBJECTIVE: Classification criteria for early-stage symptomatic knee osteoarthritis (EsSKOA) should discriminate individuals with EsSKOA from those with other causes of knee symptoms. We sought to identify conditions in the differential diagnosis of EsSKOA in adults with knee symptoms.
DESIGN: We conducted an online survey of clinicians. Those consulting monthly on at least five people with undiagnosed knee symptoms were eligible. From qualitative work and clinical experience, we developed three case scenarios representing possible EsSKOA: 1. 40-year-old with 1 month of knee stiffness and swelling; 2. 50-year-old with 8 months of knee discomfort while walking; and 3. 60-year-old with intense knee discomfort getting out of a car 1 week ago. For each scenario, participants indicated conditions on a pre-defined list that they would consider in the differential diagnosis, and the top three diagnoses based on clinical experience. The proportions that considered each condition and among the top three diagnoses for each scenario were summarized overall and by clinical discipline.
RESULTS: 127 clinicians responded (43\% female, 48\% in practice ≤15 years, 50\% university-affiliated practice, 7 clinical disciplines). Knee OA and meniscal injuries were among the top three conditions in the differential diagnosis for all three scenarios, followed by immune-mediated and crystal-induced inflammatory arthritis (scenario 1), patellofemoral pain syndrome (scenario 2), and collateral ligament injuries (scenario 3).
CONCLUSION: The differential diagnosis for EsSKOA in adults presenting with undiagnosed knee symptoms includes symptomatic established radiographic knee OA, patellofemoral pain syndrome, meniscal and collateral ligament injuries, and immune-mediated and crystal-induced inflammatory arthritis.},
	language = {eng},
	number = {9},
	journal = {Osteoarthritis and Cartilage},
	author = {Hawker, Gillian A. and King, Lauren K. and Liew, Jean W. and Wang, Qiuke and Mahmoudian, Armaghan and Jansen, Nuria E. J. and Stanaitis, Ian and Berenbaum, Francis and Das, Siddharth and Ding, Changhai and Emery, Carolyn A. and Filbay, Stephanie R. and Hochberg, Marc C. and Ishijima, Muneaki and Kloppenburg, Margreet and Lane, Nancy E. and Losina, Elena and Mobasheri, Ali and Runhaar, Jos and Appleton, C. Thomas and Turkiewicz, Aleksandra and Englund, Martin and Lohmander, L. Stefan and Haugen, Ida K. and Neogi, Tuhina and {OARSI Early-stage Symptomatic Knee Osteoarthritis Initiative}},
	month = sep,
	year = {2025},
	keywords = {Classification criteria, Diagnosis, Early-stage, Knee osteoarthritis},
	pages = {1141--1146},
}

OBJECTIVE: Classification criteria for early-stage symptomatic knee osteoarthritis (EsSKOA) should discriminate individuals with EsSKOA from those with other causes of knee symptoms. We sought to identify conditions in the differential diagnosis of EsSKOA in adults with knee symptoms. DESIGN: We conducted an online survey of clinicians. Those consulting monthly on at least five people with undiagnosed knee symptoms were eligible. From qualitative work and clinical experience, we developed three case scenarios representing possible EsSKOA: 1. 40-year-old with 1 month of knee stiffness and swelling; 2. 50-year-old with 8 months of knee discomfort while walking; and 3. 60-year-old with intense knee discomfort getting out of a car 1 week ago. For each scenario, participants indicated conditions on a pre-defined list that they would consider in the differential diagnosis, and the top three diagnoses based on clinical experience. The proportions that considered each condition and among the top three diagnoses for each scenario were summarized overall and by clinical discipline. RESULTS: 127 clinicians responded (43% female, 48% in practice ≤15 years, 50% university-affiliated practice, 7 clinical disciplines). Knee OA and meniscal injuries were among the top three conditions in the differential diagnosis for all three scenarios, followed by immune-mediated and crystal-induced inflammatory arthritis (scenario 1), patellofemoral pain syndrome (scenario 2), and collateral ligament injuries (scenario 3). CONCLUSION: The differential diagnosis for EsSKOA in adults presenting with undiagnosed knee symptoms includes symptomatic established radiographic knee OA, patellofemoral pain syndrome, meniscal and collateral ligament injuries, and immune-mediated and crystal-induced inflammatory arthritis.

@article{sjogren_molecular_2025,
	title = {Molecular treatments to reduce catabolic effects in human meniscus explant models},
	volume = {7},
	issn = {2665-9131},
	doi = {10.1016/j.ocarto.2025.100618},
	abstract = {OBJECTIVES: 1. To validate catabolic meniscus explant models induced by cytokines: interleukin-6 ​+ ​interleukin-6 receptor ​+ ​tumor necrosis factor alpha (IL6/TNF) and oncostatin M ​+ ​tumor necrosis factor alpha (OSM/TNF). 2. To evaluate three potential anti-catabolic treatments: i) dexamethasone (DEX), ii) a Link-N peptide (Link-N) and iii) a peptide from chondroadherin (CKF).
DESIGN: Healthy lateral menisci from deceased donors (n ​= ​6; age ​= ​25-70 years, 4 males, 2 females), were sliced and randomized for experimental groups (combinations of the catabolic models and anti-catabolic treatments) and a control group. Culture media were analyzed, every third day until day 18, by mass spectrometry-based proteomics. Linear mixed effect models were used to estimate differences in protein abundances between groups.
RESULTS: A total of 662 proteins were identified in all menisci. Cytokine-treated meniscus explant models showed increased release of osteoarthritis-related proteins such as matrix metalloproteinases (MMPs). For example, MMP1: IL6/TNF vs. ctrl; log2 fold-change 2.2 95 ​\% confidence interval [1.8, 2.5] and OSM/TNF vs. ctrl; log2 fold-change 2.8 [2.4, 3.1]. There was no treatment effect in explant meniscus with the addition of either Link-N or CKF. Treatment effects were, however, evident with the addition of DEX. For example, MMP1: IL6/TNF ​+ ​DEX vs. ctrl; log2 fold-change -1.8 [-2.2, -1.4] and OSM/TNF ​+ ​DEX vs. ctrl; log2 fold-change -0.3 [-0.7, 0.04].
CONCLUSION: We confirmed that both catabolic models induce changes in osteoarthritis-related proteins. DEX treatment is effective in mitigating the catabolic response in meniscus explant models and may be further explored for its effects in the treatment of meniscus degeneration.},
	language = {eng},
	number = {3},
	journal = {Osteoarthritis and Cartilage Open},
	author = {Sjögren, Amanda and Lindblom, Karin and Turkiewicz, Aleksandra and Englund, Martin and Önnerfjord, Patrik},
	month = sep,
	year = {2025},
	keywords = {Explant model, Human tissue, Meniscus, Osteoarthritis, Proteomics},
	pages = {100618},
}

OBJECTIVES: 1. To validate catabolic meniscus explant models induced by cytokines: interleukin-6 ​+ ​interleukin-6 receptor ​+ ​tumor necrosis factor alpha (IL6/TNF) and oncostatin M ​+ ​tumor necrosis factor alpha (OSM/TNF). 2. To evaluate three potential anti-catabolic treatments: i) dexamethasone (DEX), ii) a Link-N peptide (Link-N) and iii) a peptide from chondroadherin (CKF). DESIGN: Healthy lateral menisci from deceased donors (n ​= ​6; age ​= ​25-70 years, 4 males, 2 females), were sliced and randomized for experimental groups (combinations of the catabolic models and anti-catabolic treatments) and a control group. Culture media were analyzed, every third day until day 18, by mass spectrometry-based proteomics. Linear mixed effect models were used to estimate differences in protein abundances between groups. RESULTS: A total of 662 proteins were identified in all menisci. Cytokine-treated meniscus explant models showed increased release of osteoarthritis-related proteins such as matrix metalloproteinases (MMPs). For example, MMP1: IL6/TNF vs. ctrl; log2 fold-change 2.2 95 ​% confidence interval [1.8, 2.5] and OSM/TNF vs. ctrl; log2 fold-change 2.8 [2.4, 3.1]. There was no treatment effect in explant meniscus with the addition of either Link-N or CKF. Treatment effects were, however, evident with the addition of DEX. For example, MMP1: IL6/TNF ​+ ​DEX vs. ctrl; log2 fold-change -1.8 [-2.2, -1.4] and OSM/TNF ​+ ​DEX vs. ctrl; log2 fold-change -0.3 [-0.7, 0.04]. CONCLUSION: We confirmed that both catabolic models induce changes in osteoarthritis-related proteins. DEX treatment is effective in mitigating the catabolic response in meniscus explant models and may be further explored for its effects in the treatment of meniscus degeneration.

@article{kiadaliri_inflammatory_2024,
	title = {Inflammatory rheumatic diseases and the risk of drug use disorders: a register-based cohort study in {Sweden}},
	volume = {43},
	issn = {1434-9949},
	shorttitle = {Inflammatory rheumatic diseases and the risk of drug use disorders},
	doi = {10.1007/s10067-023-06755-w},
	abstract = {To investigate the association between chronic inflammatory rheumatic diseases (CIRD) and drug use disorder (DUD). Individuals aged ≥ 30 years in 2009 that met the following conditions were included: residing in the Skåne region, Sweden, with at least one healthcare contact in person and no history of DUD (ICD-10 codes F11-F16, F18-F19) during 1998-2009 (N = 649,891). CIRD was defined as the presence of rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriatic arthritis (PsA), or systemic lupus erythematosus. Treating CIRD as a time-varying exposure, we followed people from January 1, 2010 until a diagnosis of DUD, death, relocation outside the region, or December 31, 2019, whichever occurred first. We used flexible parametric survival models adjusted for attained age, sociodemographic characteristics, and coexisting conditions for data analysis. There were 64 (95\% CI 62-66) and 104 (88-123) incident DUD per 100,000 person-years among those without and with CIRD, respectively. CIRD was associated with an increased risk of DUD in age-adjusted analysis (hazard ratio [HR] 1.77, 95\% CI 1.49-2.09). Almost identical HR (1.71, 95\% CI 1.45-2.03) was estimated after adjustment for sociodemographic characteristics, and it slightly attenuated when coexisting conditions were additionally accounted for (1.47, 95\% CI 1.24-1.74). Fully adjusted HRs were 1.49 (1.21-1.85) for RA, 2.00 (1.38-2.90) for AS, and 1.58 (1.16-2.16) for PsA. More stringent definitions of CIRD didn't alter our findings. CIRD was associated with an increased risk of DUD independent of sociodemographic factors and coexisting conditions. Key Points • A register-based cohort study including 649,891 individuals aged≥30 residing in the Skåne region, Sweden, was conducted. • Chronic inflammatory rheumatic diseases were associated with higher risks of drug use disorder independent of sociodemographic factors and coexisting conditions.},
	language = {eng},
	number = {1},
	journal = {Clinical Rheumatology},
	author = {Kiadaliri, Ali and Dell'Isola, Andrea and Englund, Martin},
	month = jan,
	year = {2024},
	keywords = {Arthritis, Psoriatic, Arthritis, Rheumatoid, Chronic Disease, Cohort Studies, Cohort study, Drug use disorder, Humans, Inflammatory rheumatic diseases, Register, Rheumatic Diseases, Rheumatic Fever, Risk Factors, Spondylitis, Ankylosing, Substance-Related Disorders, Sweden},
	pages = {81--85},
}

To investigate the association between chronic inflammatory rheumatic diseases (CIRD) and drug use disorder (DUD). Individuals aged ≥ 30 years in 2009 that met the following conditions were included: residing in the Skåne region, Sweden, with at least one healthcare contact in person and no history of DUD (ICD-10 codes F11-F16, F18-F19) during 1998-2009 (N = 649,891). CIRD was defined as the presence of rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriatic arthritis (PsA), or systemic lupus erythematosus. Treating CIRD as a time-varying exposure, we followed people from January 1, 2010 until a diagnosis of DUD, death, relocation outside the region, or December 31, 2019, whichever occurred first. We used flexible parametric survival models adjusted for attained age, sociodemographic characteristics, and coexisting conditions for data analysis. There were 64 (95% CI 62-66) and 104 (88-123) incident DUD per 100,000 person-years among those without and with CIRD, respectively. CIRD was associated with an increased risk of DUD in age-adjusted analysis (hazard ratio [HR] 1.77, 95% CI 1.49-2.09). Almost identical HR (1.71, 95% CI 1.45-2.03) was estimated after adjustment for sociodemographic characteristics, and it slightly attenuated when coexisting conditions were additionally accounted for (1.47, 95% CI 1.24-1.74). Fully adjusted HRs were 1.49 (1.21-1.85) for RA, 2.00 (1.38-2.90) for AS, and 1.58 (1.16-2.16) for PsA. More stringent definitions of CIRD didn't alter our findings. CIRD was associated with an increased risk of DUD independent of sociodemographic factors and coexisting conditions. Key Points • A register-based cohort study including 649,891 individuals aged≥30 residing in the Skåne region, Sweden, was conducted. • Chronic inflammatory rheumatic diseases were associated with higher risks of drug use disorder independent of sociodemographic factors and coexisting conditions.

@article{king_you_2024,
	title = {"{You} don't put it down to arthritis": {A} qualitative study of the first symptoms recalled by individuals with knee osteoarthritis},
	volume = {6},
	issn = {2665-9131},
	shorttitle = {"{You} don't put it down to arthritis"},
	doi = {10.1016/j.ocarto.2023.100428},
	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.},
	language = {eng},
	number = {1},
	journal = {Osteoarthritis and Cartilage Open},
	author = {King, L. K. and Mahmoudian, A. and Waugh, E. J. and Stanaitis, I. and Gomes, M. and Hung, V. and MacKay, C. and Liew, J. W. and Wang, Q. and Turkiewicz, A. and Haugen, I. K. and Appleton, C. T. and Lohmander, S. and Englund, M. and Runhaar, J. and Neogi, T. and Hawker, G. A. and {OARSI Early-stage Symptomatic Knee Osteoarthritis Initiative}},
	month = mar,
	year = {2024},
	keywords = {Knee osteoarthritis, Patient-orientated research, Qualitative research, Symptoms},
	pages = {100428},
}

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.

@article{stamatis_myocardial_2024,
	title = {Myocardial infarction in a population-based cohort of patients with biopsy-confirmed giant cell arteritis in southern {Sweden}},
	volume = {10},
	issn = {2056-5933},
	doi = {10.1136/rmdopen-2023-003960},
	abstract = {OBJECTIVES: To determine the incidence rate (IR) of myocardial infarction (MI), relative risk of MI, and impact of incident MI on mortality in individuals with biopsy-confirmed giant cell arteritis (GCA).
METHODS: MIs in individuals diagnosed with GCA 1998-2016 in Skåne, Sweden were identified by searching the SWEDEHEART register, a record of all patients receiving care for MI in a coronary care unit (CCU). The regional diagnosis database, with subsequent case review, identified GCA patients receiving care for MI outside of a CCU. A cohort of 10 reference subjects for each GCA case, matched for age, sex and area of residence, was used to calculate the incidence rate ratio (IRR) of MI in GCA to that in the general population.
RESULTS: The GCA cohort comprised 1134 individuals. During 7958 person-years of follow-up, 102 were diagnosed with incident MI, yielding an IR of 12.8 per 1000 person-years (95\% CI 10.3 to 15.3). The IR was highest in the 30 days following GCA diagnosis and declined thereafter. The IRR of MI in GCA to that of the background population was 1.29 (95\% CI 1.05 to 1.59). Mortality was higher in GCA patients who experienced incident MI than in those without MI (HR 2.8; 95\% CI 2.2 to 3.6).
CONCLUSIONS: The highest incidence of MI occurs within the 30 days following diagnosis of GCA. Individuals with GCA have a moderately increased risk of MI compared with a reference population. Incident MI has a major impact on mortality in GCA.},
	language = {eng},
	number = {2},
	journal = {RMD open},
	author = {Stamatis, Pavlos and Mohammad, Moman Aladdin and Gisslander, Karl and Merkel, Peter A. and Englund, Martin and Turesson, Carl and Erlinge, David and Mohammad, Aladdin J.},
	month = apr,
	year = {2024},
	keywords = {Biopsy, Cardiovascular Diseases, Giant Cell Arteritis, Humans, Incidence, Mortality, Myocardial Infarction, Sweden, Vasculitis},
	pages = {e003960},
}

OBJECTIVES: To determine the incidence rate (IR) of myocardial infarction (MI), relative risk of MI, and impact of incident MI on mortality in individuals with biopsy-confirmed giant cell arteritis (GCA). METHODS: MIs in individuals diagnosed with GCA 1998-2016 in Skåne, Sweden were identified by searching the SWEDEHEART register, a record of all patients receiving care for MI in a coronary care unit (CCU). The regional diagnosis database, with subsequent case review, identified GCA patients receiving care for MI outside of a CCU. A cohort of 10 reference subjects for each GCA case, matched for age, sex and area of residence, was used to calculate the incidence rate ratio (IRR) of MI in GCA to that in the general population. RESULTS: The GCA cohort comprised 1134 individuals. During 7958 person-years of follow-up, 102 were diagnosed with incident MI, yielding an IR of 12.8 per 1000 person-years (95% CI 10.3 to 15.3). The IR was highest in the 30 days following GCA diagnosis and declined thereafter. The IRR of MI in GCA to that of the background population was 1.29 (95% CI 1.05 to 1.59). Mortality was higher in GCA patients who experienced incident MI than in those without MI (HR 2.8; 95% CI 2.2 to 3.6). CONCLUSIONS: The highest incidence of MI occurs within the 30 days following diagnosis of GCA. Individuals with GCA have a moderately increased risk of MI compared with a reference population. Incident MI has a major impact on mortality in GCA.

@article{dellisola_twenty-year_2024,
	title = {Twenty-year trajectories of morbidity in individuals with and without osteoarthritis},
	volume = {10},
	issn = {2056-5933},
	abstract = {OBJECTIVES: To identify multimorbidity trajectories over 20 years among incident osteoarthritis (OA) individuals and OA-free matched references.
METHODS: Cohort study using prospectively collected healthcare data from the Skåne region, Sweden ({\textasciitilde}1.4 million residents). We extracted diagnoses for OA and 67 common chronic conditions. We included individuals aged 40+ years on 31 December 2007, with incident OA between 2008 and 2009. We selected references without OA, matched on birth year, sex, and year of death or moving outside the region. We employed group-based trajectory modelling to capture morbidity count trajectories from 1998 to 2019. Individuals without any comorbidity were included as a reference group but were not included in the model.
RESULTS: We identified 9846 OA cases (mean age: 65.9 (SD 11.7), female: 58\%) and 9846 matched references. Among both cases and references, 1296 individuals did not develop chronic conditions (no-chronic-condition class). We identified four classes. At the study outset, all classes exhibited a low average number of chronic conditions (≤1). Class 1 had the slowest progression towards multimorbidity, which increased progressively in each class. Class 1 had the lowest count of chronic conditions at the end of the follow-up (mean: 2.9 (SD 1.7)), while class 4 had the highest (9.6 (2.6)). The presence of OA was associated with a 1.29 (1.12, 1.48) adjusted relative risk of belonging to class 1 up to 2.45 (2.12, 2.83) for class 4.
CONCLUSIONS: Our findings suggest that individuals with OA face an almost threefold higher risk of developing severe multimorbidity.},
	language = {eng},
	number = {2},
	journal = {RMD open},
	author = {Dell'Isola, Andrea and Recenti, Filippo and Englund, Martin and Kiadaliri, Ali},
	month = jul,
	year = {2024},
	keywords = {Adult, Aged, Chronic Disease, Comorbidity, Female, Humans, Hypertension, Incidence, Male, Middle Aged, Morbidity, Multimorbidity, Osteoarthritis, Prospective Studies, Sweden},
	pages = {e004164},
}

OBJECTIVES: To identify multimorbidity trajectories over 20 years among incident osteoarthritis (OA) individuals and OA-free matched references. METHODS: Cohort study using prospectively collected healthcare data from the Skåne region, Sweden (~1.4 million residents). We extracted diagnoses for OA and 67 common chronic conditions. We included individuals aged 40+ years on 31 December 2007, with incident OA between 2008 and 2009. We selected references without OA, matched on birth year, sex, and year of death or moving outside the region. We employed group-based trajectory modelling to capture morbidity count trajectories from 1998 to 2019. Individuals without any comorbidity were included as a reference group but were not included in the model. RESULTS: We identified 9846 OA cases (mean age: 65.9 (SD 11.7), female: 58%) and 9846 matched references. Among both cases and references, 1296 individuals did not develop chronic conditions (no-chronic-condition class). We identified four classes. At the study outset, all classes exhibited a low average number of chronic conditions (≤1). Class 1 had the slowest progression towards multimorbidity, which increased progressively in each class. Class 1 had the lowest count of chronic conditions at the end of the follow-up (mean: 2.9 (SD 1.7)), while class 4 had the highest (9.6 (2.6)). The presence of OA was associated with a 1.29 (1.12, 1.48) adjusted relative risk of belonging to class 1 up to 2.45 (2.12, 2.83) for class 4. CONCLUSIONS: Our findings suggest that individuals with OA face an almost threefold higher risk of developing severe multimorbidity.

@article{bayramoglu_deep_2024,
	title = {Deep {Learning} for {Predicting} {Progression} of {Patellofemoral} {Osteoarthritis} {Based} on {Lateral} {Knee} {Radiographs}, {Demographic} {Data}, and {Symptomatic} {Assessments}},
	volume = {63},
	issn = {2511-705X},
	doi = {10.1055/a-2305-2115},
	abstract = {OBJECTIVE: In this study, we propose a novel framework that utilizes deep learning and attention mechanisms to predict the radiographic progression of patellofemoral osteoarthritis (PFOA) over a period of 7 years.
MATERIAL AND METHODS: This study included subjects (1,832 subjects, 3,276 knees) from the baseline of the Multicenter Osteoarthritis Study (MOST). Patellofemoral joint regions of interest were identified using an automated landmark detection tool (BoneFinder) on lateral knee X-rays. An end-to-end deep learning method was developed for predicting PFOA progression based on imaging data in a five-fold cross-validation setting. To evaluate the performance of the models, a set of baselines based on known risk factors were developed and analyzed using gradient boosting machine (GBM). Risk factors included age, sex, body mass index, and Western Ontario and McMaster Universities Arthritis Index score, and the radiographic osteoarthritis stage of the tibiofemoral joint (Kellgren and Lawrence [KL] score). Finally, to increase predictive power, we trained an ensemble model using both imaging and clinical data.
RESULTS: Among the individual models, the performance of our deep convolutional neural network attention model achieved the best performance with an area under the receiver operating characteristic curve (AUC) of 0.856 and average precision (AP) of 0.431, slightly outperforming the deep learning approach without attention (AUC = 0.832, AP = 0.4) and the best performing reference GBM model (AUC = 0.767, AP = 0.334). The inclusion of imaging data and clinical variables in an ensemble model allowed statistically more powerful prediction of PFOA progression (AUC = 0.865, AP = 0.447), although the clinical significance of this minor performance gain remains unknown. The spatial attention module improved the predictive performance of the backbone model, and the visual interpretation of attention maps focused on the joint space and the regions where osteophytes typically occur.
CONCLUSION: This study demonstrated the potential of machine learning models to predict the progression of PFOA using imaging and clinical variables. These models could be used to identify patients who are at high risk of progression and prioritize them for new treatments. However, even though the accuracy of the models were excellent in this study using the MOST dataset, they should be still validated using external patient cohorts in the future.},
	language = {eng},
	number = {1-02},
	journal = {Methods of Information in Medicine},
	author = {Bayramoglu, Neslihan and Englund, Martin and Haugen, Ida K. and Ishijima, Muneaki and Saarakkala, Simo},
	month = may,
	year = {2024},
	keywords = {Aged, Deep Learning, Demography, Disease Progression, Female, Humans, Male, Middle Aged, Osteoarthritis, Knee, Patellofemoral Joint, Radiography},
	pages = {1--10},
}

OBJECTIVE: In this study, we propose a novel framework that utilizes deep learning and attention mechanisms to predict the radiographic progression of patellofemoral osteoarthritis (PFOA) over a period of 7 years. MATERIAL AND METHODS: This study included subjects (1,832 subjects, 3,276 knees) from the baseline of the Multicenter Osteoarthritis Study (MOST). Patellofemoral joint regions of interest were identified using an automated landmark detection tool (BoneFinder) on lateral knee X-rays. An end-to-end deep learning method was developed for predicting PFOA progression based on imaging data in a five-fold cross-validation setting. To evaluate the performance of the models, a set of baselines based on known risk factors were developed and analyzed using gradient boosting machine (GBM). Risk factors included age, sex, body mass index, and Western Ontario and McMaster Universities Arthritis Index score, and the radiographic osteoarthritis stage of the tibiofemoral joint (Kellgren and Lawrence [KL] score). Finally, to increase predictive power, we trained an ensemble model using both imaging and clinical data. RESULTS: Among the individual models, the performance of our deep convolutional neural network attention model achieved the best performance with an area under the receiver operating characteristic curve (AUC) of 0.856 and average precision (AP) of 0.431, slightly outperforming the deep learning approach without attention (AUC = 0.832, AP = 0.4) and the best performing reference GBM model (AUC = 0.767, AP = 0.334). The inclusion of imaging data and clinical variables in an ensemble model allowed statistically more powerful prediction of PFOA progression (AUC = 0.865, AP = 0.447), although the clinical significance of this minor performance gain remains unknown. The spatial attention module improved the predictive performance of the backbone model, and the visual interpretation of attention maps focused on the joint space and the regions where osteophytes typically occur. CONCLUSION: This study demonstrated the potential of machine learning models to predict the progression of PFOA using imaging and clinical variables. These models could be used to identify patients who are at high risk of progression and prioritize them for new treatments. However, even though the accuracy of the models were excellent in this study using the MOST dataset, they should be still validated using external patient cohorts in the future.

@article{haugen_2023_2024,
	title = {2023 {EULAR} classification criteria for hand osteoarthritis},
	volume = {0},
	issn = {1468-2060},
	doi = {10.1136/ard-2023-225073},
	abstract = {OBJECTIVES: The objective of this study is to develop classification criteria for overall hand osteoarthritis (OA), interphalangeal OA and thumb base OA based on self-reported data and radiographic features.
METHODS: The classification criteria sets were developed in three phases. In phase 1, we identified criteria that discriminated hand OA from controls. In phase 2, we used a consensus-based decision analysis approach to derive a clinician-based evaluation of the relative importance of the criteria. In phase 3, we refined the scoring system, determined the cut-offs for disease classification and compared the sensitivity and specificity of the European Alliance of Associations for Rheumatology (EULAR) criteria with the 1990 American College of Rheumatology (ACR) criteria.
RESULTS: In persons with hand symptoms and no other disease (including psoriasis) or acute injury that can explain the hand symptoms (mandatory criteria), hand OA can be classified based on age, duration of morning stiffness, number of joints with osteophytes and joint space narrowing, and concordance between symptoms and radiographic findings. Using a sum of scores based on each diagnostic element, overall hand OA can be classified if a person achieves 9 or more points on a 0-15 scale. The cut-off for interphalangeal OA and thumb base OA is 8 points. While the EULAR criteria demonstrated better sensitivity than the ACR criteria in the phase 1 data set, the performance of the two criteria sets was similar in two external cohorts.
CONCLUSIONS: International experts developed the EULAR criteria to classify overall hand OA, interphalangeal OA and thumb base OA in clinical studies using a rigorous methodology.},
	language = {eng},
	journal = {Annals of the Rheumatic Diseases},
	author = {Haugen, Ida K. and Felson, David T. and Abhishek, Abhishek and Berenbaum, Francis and Bierma-Zeinstra, Sita and Dziedzic, Krysia S. and Edwards, John James and Englund, Martin and Hermann-Eriksen, Merete and Herrero-Beaumont, Gabriel and Hill, Catherine and Ishimori, Mariko L. and Jonsson, Helgi and Karjalainen, Teemu and Leung, Ying Ying and Maheu, Emmanuel and Mallen, Christian D. and Marshall, Michelle and Moe, Rikke H. and Ramonda, Roberta and Ritschl, Valentin and Ritt, Marco Jpf and Stamm, Tanja A. and Szekanecz, Zoltan and van der Giesen, Florus and van de Stadt, Lotte A. and van der Meulen, Coen and Wittoek, Ruth and Greibrokk, Elsie and Laheij, Hellen and Kloppenburg, Margreet},
	month = may,
	year = {2024},
	keywords = {Epidemiology, Osteoarthritis, Patient Reported Outcome Measures},
	pages = {1--8},
}

OBJECTIVES: The objective of this study is to develop classification criteria for overall hand osteoarthritis (OA), interphalangeal OA and thumb base OA based on self-reported data and radiographic features. METHODS: The classification criteria sets were developed in three phases. In phase 1, we identified criteria that discriminated hand OA from controls. In phase 2, we used a consensus-based decision analysis approach to derive a clinician-based evaluation of the relative importance of the criteria. In phase 3, we refined the scoring system, determined the cut-offs for disease classification and compared the sensitivity and specificity of the European Alliance of Associations for Rheumatology (EULAR) criteria with the 1990 American College of Rheumatology (ACR) criteria. RESULTS: In persons with hand symptoms and no other disease (including psoriasis) or acute injury that can explain the hand symptoms (mandatory criteria), hand OA can be classified based on age, duration of morning stiffness, number of joints with osteophytes and joint space narrowing, and concordance between symptoms and radiographic findings. Using a sum of scores based on each diagnostic element, overall hand OA can be classified if a person achieves 9 or more points on a 0-15 scale. The cut-off for interphalangeal OA and thumb base OA is 8 points. While the EULAR criteria demonstrated better sensitivity than the ACR criteria in the phase 1 data set, the performance of the two criteria sets was similar in two external cohorts. CONCLUSIONS: International experts developed the EULAR criteria to classify overall hand OA, interphalangeal OA and thumb base OA in clinical studies using a rigorous methodology.

@article{kiadaliri_rheumatic_2024,
	title = {Rheumatic and {Musculoskeletal} {Diseases} and {Risk} of {Dementia}: {A} {Nested} {Case}-{Control} {Study}},
	volume = {6},
	issn = {2578-5745},
	shorttitle = {Rheumatic and {Musculoskeletal} {Diseases} and {Risk} of {Dementia}},
	doi = {10.1002/acr2.11705},
	abstract = {OBJECTIVE: To investigate the associations between rheumatic and musculoskeletal diseases (RMDs) and incident dementia using population register-based data.
METHODS: This nested case-control study was conducted based on a cohort of residents in the Skåne region, Sweden, aged 50 years and older in 2009 without doctor-diagnosed dementia during 1998 to 2009 (n = 402,825). Individuals with a new main diagnosis of dementia during 2010 to 2019 were identified as incident patients with dementia (n = 22,131). Controls without diagnosed dementia were randomly matched 1:1 by sex, age, and Elixhauser comorbidity index using incidence density sampling. Separate conditional logistic regression analyses adjusted for confounders were fitted for the following RMDs, diagnosed at least 2 years before dementia diagnosis as exposure: gout, osteoarthritis, rheumatoid arthritis, spondyloarthropathies (SpA), and systemic connective tissue disorders. Subgroup analyses by dementia subtype, sex, age, comorbidity, and RMDs/dementia identification were conducted.
RESULTS: Although gout (adjusted rate ratio 0.88; 95\% confidence interval 0.79-0.97), osteoarthritis (0.92; 0.88-0.96), and systemic connective tissue disorders (0.91; 0.83-0.99) were associated with decreased risk of dementia, the associations for rheumatoid arthritis (1.05; 0.92-1.19) and SpA (1.17; 0.94-1.45) were inconclusive. The associations between RMDs and incident dementia were similar across sex, age, and comorbidity subgroups with a few exceptions (eg, an adjusted rate ratio of 0.99 [95\% confidence interval 0.71-1.39] in males vs 1.31 [0.99-1.74] in female patients for SpA).
CONCLUSION: Persons with diagnosed RMDs seem to have comparable or slightly lower risks of developing dementia compared with those without known RMD.},
	language = {eng},
	number = {8},
	journal = {ACR open rheumatology},
	author = {Kiadaliri, Ali and Dell'Isola, Andrea and Turkiewicz, Aleksandra and Englund, Martin},
	month = aug,
	year = {2024},
	pages = {504--510},
}

OBJECTIVE: To investigate the associations between rheumatic and musculoskeletal diseases (RMDs) and incident dementia using population register-based data. METHODS: This nested case-control study was conducted based on a cohort of residents in the Skåne region, Sweden, aged 50 years and older in 2009 without doctor-diagnosed dementia during 1998 to 2009 (n = 402,825). Individuals with a new main diagnosis of dementia during 2010 to 2019 were identified as incident patients with dementia (n = 22,131). Controls without diagnosed dementia were randomly matched 1:1 by sex, age, and Elixhauser comorbidity index using incidence density sampling. Separate conditional logistic regression analyses adjusted for confounders were fitted for the following RMDs, diagnosed at least 2 years before dementia diagnosis as exposure: gout, osteoarthritis, rheumatoid arthritis, spondyloarthropathies (SpA), and systemic connective tissue disorders. Subgroup analyses by dementia subtype, sex, age, comorbidity, and RMDs/dementia identification were conducted. RESULTS: Although gout (adjusted rate ratio 0.88; 95% confidence interval 0.79-0.97), osteoarthritis (0.92; 0.88-0.96), and systemic connective tissue disorders (0.91; 0.83-0.99) were associated with decreased risk of dementia, the associations for rheumatoid arthritis (1.05; 0.92-1.19) and SpA (1.17; 0.94-1.45) were inconclusive. The associations between RMDs and incident dementia were similar across sex, age, and comorbidity subgroups with a few exceptions (eg, an adjusted rate ratio of 0.99 [95% confidence interval 0.71-1.39] in males vs 1.31 [0.99-1.74] in female patients for SpA). CONCLUSION: Persons with diagnosed RMDs seem to have comparable or slightly lower risks of developing dementia compared with those without known RMD.

@article{dellisola_coexistence_2024,
	title = {The coexistence of diabetes, hypertension and obesity is associated with worse pain outcomes following exercise for osteoarthritis: {A} cohort study on 80,893 patients},
	volume = {32},
	issn = {1522-9653},
	shorttitle = {The coexistence of diabetes, hypertension and obesity is associated with worse pain outcomes following exercise for osteoarthritis},
	doi = {10.1016/j.joca.2024.05.005},
	abstract = {OBJECTIVES: To investigate how the co-occurrence of diabetes, hypertension and overweight/obesity is associated with pain following an exercise intervention for knee and hip osteoarthritis (OA).
METHODS: Register-based cohort study. We included people from the Swedish Osteoarthritis Register who underwent education and exercise for knee or hip OA. Diabetes and hypertension were defined using medical records and dispensation of medication. Body Mass Index (BMI) was used to identify people with overweight (≥25 to {\textless}30), and obesity (≥30). We used linear mixed-effect models with patients nested into clinics to estimate the associations between the exposures and pain (Numeric Rating Scale 0-10), adjusting for age, sex, education, and physical activity.
RESULTS: We analysed 80,893 patients with knee or hip OA. The accumulation of metabolic conditions was associated with worse pain at baseline and follow-ups. When obesity, hypertension and diabetes coexisted, patients treated for knee OA reported more pain at baseline (adjusted mean pain difference 0.9 [95 \%CI: 0.8; 1.0]), 3 months (1.0 [0.9; 1.1]) and 12 months (1.3 [1.1; 1.4]) compared to those without any of the conditions. Similar results were observed for patients treated for hip OA when obesity, hypertension and diabetes coexisted (baseline (0.7 [0.5; 0.8], 3 (0.8[0.6; 1.0]) and 12 months (1.1[0.8; 1.3]).
CONCLUSIONS: When diabetes, hypertension and obesity coexist with OA, patients not only experience heightened baseline pain compared to metabolically healthy individuals, but the disparity increases after an education and exercise intervention suggesting that a one-size-fits-all approach may be inadequate in addressing the complex interplay between metabolic health and OA.},
	language = {eng},
	number = {10},
	journal = {Osteoarthritis and Cartilage},
	author = {Dell'Isola, Andrea and Vinblad, Johanna and Turkiewicz, Aleksandra and Kiadaliri, Ali and Abbott, Allan and Rolfson, Ola and Lohmander, Stefan L. and Jönsson, Therese and Englund, Martin},
	month = oct,
	year = {2024},
	keywords = {Aged, Arthralgia, Body Mass Index, Cohort Studies, Comorbidity, Diabetes, Diabetes Mellitus, Exercise, Exercise Therapy, Female, Humans, Hypertension, Male, Middle Aged, Obesity, Osteoarthritis, Osteoarthritis, Hip, Osteoarthritis, Knee, Overweight, Pain Measurement, Registries, Sweden},
	pages = {1308--1318},
}

OBJECTIVES: To investigate how the co-occurrence of diabetes, hypertension and overweight/obesity is associated with pain following an exercise intervention for knee and hip osteoarthritis (OA). METHODS: Register-based cohort study. We included people from the Swedish Osteoarthritis Register who underwent education and exercise for knee or hip OA. Diabetes and hypertension were defined using medical records and dispensation of medication. Body Mass Index (BMI) was used to identify people with overweight (≥25 to \textless30), and obesity (≥30). We used linear mixed-effect models with patients nested into clinics to estimate the associations between the exposures and pain (Numeric Rating Scale 0-10), adjusting for age, sex, education, and physical activity. RESULTS: We analysed 80,893 patients with knee or hip OA. The accumulation of metabolic conditions was associated with worse pain at baseline and follow-ups. When obesity, hypertension and diabetes coexisted, patients treated for knee OA reported more pain at baseline (adjusted mean pain difference 0.9 [95 %CI: 0.8; 1.0]), 3 months (1.0 [0.9; 1.1]) and 12 months (1.3 [1.1; 1.4]) compared to those without any of the conditions. Similar results were observed for patients treated for hip OA when obesity, hypertension and diabetes coexisted (baseline (0.7 [0.5; 0.8], 3 (0.8[0.6; 1.0]) and 12 months (1.1[0.8; 1.3]). CONCLUSIONS: When diabetes, hypertension and obesity coexist with OA, patients not only experience heightened baseline pain compared to metabolically healthy individuals, but the disparity increases after an education and exercise intervention suggesting that a one-size-fits-all approach may be inadequate in addressing the complex interplay between metabolic health and OA.

@article{magnusson_shared_2024,
	title = {Shared genetic factors between osteoarthritis and cardiovascular disease may underlie common etiology},
	volume = {15},
	issn = {2041-1723},
	doi = {10.1038/s41467-024-53812-2},
	abstract = {Osteoarthritis is one of the most common musculoskeletal diseases and increases the risk of severe cardiovascular disease, like heart attack and stroke. In some individuals, osteoarthritis and cardiovascular disease will co-occur. This co-occurrence might be due to shared risk factors, for example high age, lifestyle factors and/or a shared genetic liability for the two diseases. Here, we show that the correlation between osteoarthritis and cardiovascular disease can be explained by shared genetic factors, independent of high age and body weight, and also likely independent of lifestyle factors, like smoking and physical activity level. Findings suggest that genetic factors that are shared for osteoarthritis and cardiovascular disease may contribute to both diseases. Thus, the prevailing idea that osteoarthritis is predominantly a risk factor for cardiovascular disease is challenged. Our findings imply that the current diagnostic boundaries between these diseases may need to be re-evaluated.},
	language = {eng},
	number = {1},
	journal = {Nature Communications},
	author = {Magnusson, Karin and Turkiewicz, Aleksandra and Dell'Isola, Andrea and Englund, Martin},
	month = nov,
	year = {2024},
	keywords = {Adult, Aged, Cardiovascular Diseases, Female, Genetic Predisposition to Disease, Humans, Life Style, Male, Middle Aged, Osteoarthritis, Polymorphism, Single Nucleotide, Risk Factors, Smoking},
	pages = {9569},
}

Osteoarthritis is one of the most common musculoskeletal diseases and increases the risk of severe cardiovascular disease, like heart attack and stroke. In some individuals, osteoarthritis and cardiovascular disease will co-occur. This co-occurrence might be due to shared risk factors, for example high age, lifestyle factors and/or a shared genetic liability for the two diseases. Here, we show that the correlation between osteoarthritis and cardiovascular disease can be explained by shared genetic factors, independent of high age and body weight, and also likely independent of lifestyle factors, like smoking and physical activity level. Findings suggest that genetic factors that are shared for osteoarthritis and cardiovascular disease may contribute to both diseases. Thus, the prevailing idea that osteoarthritis is predominantly a risk factor for cardiovascular disease is challenged. Our findings imply that the current diagnostic boundaries between these diseases may need to be re-evaluated.

@article{neogi_frequent_2024,
	title = {Frequent use of prescription {NSAIDs} among people with knee or hip osteoarthritis despite contraindications to or precautions with {NSAIDs}},
	volume = {32},
	issn = {1522-9653},
	doi = {10.1016/j.joca.2024.07.010},
	abstract = {OBJECTIVE: To describe the use of non-steroidal anti-inflammatory drugs (NSAID), opioids, and physiotherapy (PT) among persons with newly diagnosed knee or hip osteoarthritis (OA) with and without NSAID contraindications or precautions.
DESIGN: We used population-based register data to identify adults aged ≥35 as of January 1, 2014, residing in Skåne region (Sweden) between 2004 and 2013, without a previous knee or hip OA diagnosis. Among this cohort, we identified people with incident knee or hip OA diagnosis between 2014 and 2018 and the presence of contraindications to or precautions for oral NSAIDs at the time of OA diagnosis. We estimated the risk of 1) regular oral NSAID use, 2) regular opioid use, and 3) PT during the first year after diagnosis among those with vs. without contraindications or precautions using confounder-adjusted logistic regression with standardization.
RESULTS: We identified 35,173 persons with newly diagnosed OA, of whom 3257 and 8351 had ≥1 contraindication to oral NSAIDs and ≥1 precaution, respectively. Overall, 27\% of individuals used oral NSAIDs (with or without opioids or PT), 10\% used opioids, and 57\% attended PT. Among patients with contraindications, 21\% used oral NSAIDs compared to 31\% without (absolute adjusted difference -0.06 (95\% CIs: -0.08, -0.05)), 53\% vs 59\% used PT (adjusted difference -0.03 (-0.05, -0.01)), while 14\% vs. 8\% had prescribed dispensed opioids (adjusted difference 0.02 (0.01, 0.03)). Similar results were observed for those with precautions.
CONCLUSIONS: We highlight the need for safer treatment options. People with OA and contraindications/precautions to NSAIDs have a higher risk of opioid use, slightly lower risk of PT use, and continue to be prescribed NSAIDs.},
	language = {eng},
	number = {12},
	journal = {Osteoarthritis and Cartilage},
	author = {Neogi, Tuhina and Dell'Isola, Andrea and Englund, Martin and Turkiewicz, Aleksandra},
	month = dec,
	year = {2024},
	keywords = {Adult, Aged, Aged, 80 and over, Analgesics, Opioid, Anti-Inflammatory Agents, Non-Steroidal, Contraindications, Contraindications, Drug, Female, Humans, Male, Middle Aged, NSAIDs, Osteoarthritis, Osteoarthritis, Hip, Osteoarthritis, Knee, Physical Therapy Modalities, Registries},
	pages = {1628--1635},
}

OBJECTIVE: To describe the use of non-steroidal anti-inflammatory drugs (NSAID), opioids, and physiotherapy (PT) among persons with newly diagnosed knee or hip osteoarthritis (OA) with and without NSAID contraindications or precautions. DESIGN: We used population-based register data to identify adults aged ≥35 as of January 1, 2014, residing in Skåne region (Sweden) between 2004 and 2013, without a previous knee or hip OA diagnosis. Among this cohort, we identified people with incident knee or hip OA diagnosis between 2014 and 2018 and the presence of contraindications to or precautions for oral NSAIDs at the time of OA diagnosis. We estimated the risk of 1) regular oral NSAID use, 2) regular opioid use, and 3) PT during the first year after diagnosis among those with vs. without contraindications or precautions using confounder-adjusted logistic regression with standardization. RESULTS: We identified 35,173 persons with newly diagnosed OA, of whom 3257 and 8351 had ≥1 contraindication to oral NSAIDs and ≥1 precaution, respectively. Overall, 27% of individuals used oral NSAIDs (with or without opioids or PT), 10% used opioids, and 57% attended PT. Among patients with contraindications, 21% used oral NSAIDs compared to 31% without (absolute adjusted difference -0.06 (95% CIs: -0.08, -0.05)), 53% vs 59% used PT (adjusted difference -0.03 (-0.05, -0.01)), while 14% vs. 8% had prescribed dispensed opioids (adjusted difference 0.02 (0.01, 0.03)). Similar results were observed for those with precautions. CONCLUSIONS: We highlight the need for safer treatment options. People with OA and contraindications/precautions to NSAIDs have a higher risk of opioid use, slightly lower risk of PT use, and continue to be prescribed NSAIDs.

@article{shakya_prevalence_2024,
	title = {Prevalence and classification of meniscal calcifications in the human knee},
	volume = {32},
	issn = {1522-9653},
	doi = {10.1016/j.joca.2024.07.013},
	abstract = {OBJECTIVE: To investigate the occurrence of meniscal calcifications in individuals with and without knee osteoarthritis (OA). Additionally, we aim to identify the specific types of calcifications: basic calcium phosphate (BCP) and calcium pyrophosphate dihydrate (CPP).
METHOD: We analyzed 82 meniscal posterior horn samples (medial and lateral) collected from 41 human subjects. Among them, 20 individuals underwent total knee replacement due to medial compartment OA, while 21 deceased donors had no known knee OA. The assessment of meniscal calcifications and Pauli's histopathological scoring was conducted using histological sections. Furthermore, adjacent sections underwent measurement using Raman spectroscopy to characterize BCP and CPP calcifications based on their distinct spectral fingerprints.
RESULTS: All OA individuals exhibited calcifications in at least one meniscus, compared to 9.5\% (95\%CI 1\%, 30\%) of donors. Among 35 OA menisci with calcifications, 28(80\%) had BCP, 5(14\%) had CPP and 2(6\%) had both types. In 4 donor menisci, 3(75\%) had CPP while 1(25\%) had both types. We estimated the association between Pauli score and presence of BCP in OA individuals, yielding an odds ratio of 2.1 (95\%CI 0.8, 5.3) per 1 Pauli score. The association between Pauli score and presence of CPP (in whole study sample) seemed weaker, with odds ratio of 1.3 (95\%CI 1.1, 1.7).
CONCLUSION: The presence of BCP was predominant in menisci of OA individuals, whereas CPP exhibited similar prevalence in individuals with and without OA. The formation of BCP crystals in menisci may represent an important and specific characteristic of OA disease process that warrants further attention.},
	language = {eng},
	number = {11},
	journal = {Osteoarthritis and Cartilage},
	author = {Shakya, Bijay Ratna and Karjalainen, Ville-Pauli and Hellberg, Iida and Finnilä, Mikko A. J. and Elkhouly, Khaled and Sjögren, Amanda and Turkiewicz, Aleksandra and Önnerfjord, Patrik and Hughes, Velocity and Tjörnstrand, Jon and Englund, Martin and Saarakkala, Simo},
	month = nov,
	year = {2024},
	keywords = {Aged, Aged, 80 and over, Arthroplasty, Replacement, Knee, Basic calcium phosphate, Calcification, Calcinosis, Calcium Phosphates, Calcium Pyrophosphate, Calcium pyrophosphate, Chondrocalcinosis, Female, Humans, Male, Menisci, Tibial, Meniscus, Middle Aged, Osteoarthritis, Osteoarthritis, Knee, Prevalence, Raman spectroscopy, Spectrum Analysis, Raman},
	pages = {1443--1451},
}

OBJECTIVE: To investigate the occurrence of meniscal calcifications in individuals with and without knee osteoarthritis (OA). Additionally, we aim to identify the specific types of calcifications: basic calcium phosphate (BCP) and calcium pyrophosphate dihydrate (CPP). METHOD: We analyzed 82 meniscal posterior horn samples (medial and lateral) collected from 41 human subjects. Among them, 20 individuals underwent total knee replacement due to medial compartment OA, while 21 deceased donors had no known knee OA. The assessment of meniscal calcifications and Pauli's histopathological scoring was conducted using histological sections. Furthermore, adjacent sections underwent measurement using Raman spectroscopy to characterize BCP and CPP calcifications based on their distinct spectral fingerprints. RESULTS: All OA individuals exhibited calcifications in at least one meniscus, compared to 9.5% (95%CI 1%, 30%) of donors. Among 35 OA menisci with calcifications, 28(80%) had BCP, 5(14%) had CPP and 2(6%) had both types. In 4 donor menisci, 3(75%) had CPP while 1(25%) had both types. We estimated the association between Pauli score and presence of BCP in OA individuals, yielding an odds ratio of 2.1 (95%CI 0.8, 5.3) per 1 Pauli score. The association between Pauli score and presence of CPP (in whole study sample) seemed weaker, with odds ratio of 1.3 (95%CI 1.1, 1.7). CONCLUSION: The presence of BCP was predominant in menisci of OA individuals, whereas CPP exhibited similar prevalence in individuals with and without OA. The formation of BCP crystals in menisci may represent an important and specific characteristic of OA disease process that warrants further attention.

@article{englund_osteoarthritis_2023,
	title = {Osteoarthritis, part of life or a curable disease? {A} bird's-eye view},
	volume = {293},
	issn = {1365-2796},
	shorttitle = {Osteoarthritis, part of life or a curable disease?},
	url = {https://onlinelibrary.wiley.com/doi/full/10.1111/joim.13634},
	doi = {10.1111/joim.13634},
	abstract = {Osteoarthritis (OA) is a chronic joint disease caused by disruption of joint homeostasis by a variety of systemic and biomechanical factors. The disease is characterized by degradation of cartilage and other joint tissues, and low-grade inflammation which may result in pain, reduced function, and disability. The disease appears to have ancient origins, with findings of OA recognized in fossilized bones from birdlike dinosaurs living some 130 million years ago. Today, the burden of OA in the world's population is steadily increasing due to aging and often rising rates of obesity. Structural findings, indicative of the disease, are also frequent in asymptomatic persons, which make the distinction between disease and normal aging sometimes challenging. OA is frequently associated with comorbidity in the form of obesity, cardiovascular disease, and depressive symptoms. The current management and treatments largely rely on contextual factors, and the actual effects of the intended therapeutic element of today's interventions are minor. The different mechanistic pathways (endotypes) and clinical characteristics (phenotypes) of OA make the development of disease-modifying treatments challenging. Current development of drug candidates, aimed to restore joint homeostasis, is mainly targeting either inhibition of catabolic factors or stimulation of anabolic factors. However, there is yet no breakthrough in stage III clinical trials. Earlier diagnosis, better knowledge of endotypes-for example, by new insights into soluble biomarkers, and compositional imaging-and more careful selection of patients into clinical trials are possible tools to aid development of future therapies.},
	language = {eng},
	number = {6},
	journal = {Journal of Internal Medicine},
	author = {Englund, Martin},
	month = apr,
	year = {2023},
	keywords = {epidemiology, etiology, osteoarthritis, pain, therapeutics},
	pages = {681--693},
}

Osteoarthritis (OA) is a chronic joint disease caused by disruption of joint homeostasis by a variety of systemic and biomechanical factors. The disease is characterized by degradation of cartilage and other joint tissues, and low-grade inflammation which may result in pain, reduced function, and disability. The disease appears to have ancient origins, with findings of OA recognized in fossilized bones from birdlike dinosaurs living some 130 million years ago. Today, the burden of OA in the world's population is steadily increasing due to aging and often rising rates of obesity. Structural findings, indicative of the disease, are also frequent in asymptomatic persons, which make the distinction between disease and normal aging sometimes challenging. OA is frequently associated with comorbidity in the form of obesity, cardiovascular disease, and depressive symptoms. The current management and treatments largely rely on contextual factors, and the actual effects of the intended therapeutic element of today's interventions are minor. The different mechanistic pathways (endotypes) and clinical characteristics (phenotypes) of OA make the development of disease-modifying treatments challenging. Current development of drug candidates, aimed to restore joint homeostasis, is mainly targeting either inhibition of catabolic factors or stimulation of anabolic factors. However, there is yet no breakthrough in stage III clinical trials. Earlier diagnosis, better knowledge of endotypes-for example, by new insights into soluble biomarkers, and compositional imaging-and more careful selection of patients into clinical trials are possible tools to aid development of future therapies.

@article{liew_scoping_2023,
	title = {A scoping review of how early-stage knee osteoarthritis has been defined},
	volume = {293},
	issn = {1063-4584},
	url = {https://www.sciencedirect.com/science/article/pii/S1063458423007975},
	doi = {10.1016/j.joca.2023.04.015},
	abstract = {Background
Early-stage knee osteoarthritis (KOA) classification criteria will enable consistent identification and trial recruitment of individuals with knee osteoarthritis (OA) at an earlier stage of the disease when interventions may be more effective. Toward this goal, we identified how early-stage KOA has been defined in the literature.
Methods
We performed a scoping literature review in PubMed, EMBASE, Cochrane, and Web of Science, including human studies where early-stage KOA was included as a study population or outcome. Extracted data included demographics, symptoms/history, examination, laboratory, imaging, performance-based measures, gross inspection/histopathologic domains, and the components of composite early-stage KOA definitions.
Results
Of 6142 articles identified, 211 were included in data synthesis. An early-stage KOA definition was used for study inclusion in 194 studies, to define study outcomes in 11 studies, and in the context of new criteria development or validation in six studies. The element most often used to define early-stage KOA was Kellgren–Lawrence (KL) grade (151 studies, 72\%), followed by symptoms (118 studies, 56\%), and demographic characteristics (73 studies, 35\%); 14 studies (6\%) used previously developed early-stage KOA composite criteria. Among studies defining early-stage KOA radiographically, 52 studies defined early-stage KOA by KL grade alone; of these 52, 44 (85\%) studies included individuals with KL grade 2 or higher in their definitions.
Conclusion
Early-stage KOA is variably defined in the published literature. Most studies included KL grades of 2 or higher within their definitions, which reflects established or later-stage OA. These findings underscore the need to develop and validate classification criteria for early-stage KOA.},
	language = {en},
	number = {6},
	urldate = {2023-06-07},
	journal = {Osteoarthritis and Cartilage},
	author = {Liew, Jean W. and King, Lauren K. and Mahmoudian, Armaghan and Wang, Qiuke and Atkinson, Hayden F. and Flynn, David B. and Appleton, C. Thomas and Englund, Martin and Haugen, Ida K. and Lohmander, L. Stefan and Runhaar, Jos and Neogi, Tuhina and Hawker, Gillian},
	month = may,
	year = {2023},
	note = {Number: 6},
	keywords = {Classification criteria, Early-stage osteoarthritis, Knee osteoarthritis, Osteoarthritis, Scoping review, Symptomatic knee osteoarthritis},
	pages = {681--693},
}

Background Early-stage knee osteoarthritis (KOA) classification criteria will enable consistent identification and trial recruitment of individuals with knee osteoarthritis (OA) at an earlier stage of the disease when interventions may be more effective. Toward this goal, we identified how early-stage KOA has been defined in the literature. Methods We performed a scoping literature review in PubMed, EMBASE, Cochrane, and Web of Science, including human studies where early-stage KOA was included as a study population or outcome. Extracted data included demographics, symptoms/history, examination, laboratory, imaging, performance-based measures, gross inspection/histopathologic domains, and the components of composite early-stage KOA definitions. Results Of 6142 articles identified, 211 were included in data synthesis. An early-stage KOA definition was used for study inclusion in 194 studies, to define study outcomes in 11 studies, and in the context of new criteria development or validation in six studies. The element most often used to define early-stage KOA was Kellgren–Lawrence (KL) grade (151 studies, 72%), followed by symptoms (118 studies, 56%), and demographic characteristics (73 studies, 35%); 14 studies (6%) used previously developed early-stage KOA composite criteria. Among studies defining early-stage KOA radiographically, 52 studies defined early-stage KOA by KL grade alone; of these 52, 44 (85%) studies included individuals with KL grade 2 or higher in their definitions. Conclusion Early-stage KOA is variably defined in the published literature. Most studies included KL grades of 2 or higher within their definitions, which reflects established or later-stage OA. These findings underscore the need to develop and validate classification criteria for early-stage KOA.

@article{englund_emperors_2023,
	title = {The {Emperor}’s {New} {Clothes}?},
	volume = {31},
	issn = {1063-4584},
	url = {https://www.sciencedirect.com/science/article/pii/S1063458423005952},
	doi = {10.1016/j.joca.2023.02.001},
	language = {en},
	number = {5},
	urldate = {2023-02-13},
	journal = {Osteoarthritis and Cartilage},
	author = {Englund, Martin and Turkiewicz, Aleksandra},
	month = feb,
	year = {2023},
	pages = {549--551},
}

@article{rathmann_stable_2023,
	chapter = {Epidemiology},
	title = {Stable incidence but increase in prevalence of {ANCA}-associated vasculitis in southern {Sweden}: a 23-year study},
	volume = {9},
	copyright = {© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/.},
	issn = {2056-5933},
	shorttitle = {Stable incidence but increase in prevalence of {ANCA}-associated vasculitis in southern {Sweden}},
	url = {https://rmdopen.bmj.com/content/9/1/e002949},
	doi = {10.1136/rmdopen-2022-002949},
	abstract = {Objective To update the epidemiology of anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) in a defined geographical area of southern Sweden.
Methods The study area comprised 14 municipalities with a combined adult population (≥18 years) of 623 872 in 2019. All cases diagnosed with AAV in 1997–2019 in the study area were included in the estimate of incidence. Diagnosis of AAV was verified by case record review, and cases were classified using the European Medicines Agency algorithm. Point prevalence was estimated on 01 January 2020.
Results Three hundred and seventy-four patients (median age 67.5 years, 47\% female) were diagnosed with new-onset AAV during the study period. One hundred and ninety-two were classified as granulomatosis with polyangiitis (GPA), 159 as microscopic polyangiitis (MPA) and 23 as EGPA. The average annual incidence/million adults was 30.1 (95\% CI 27.0 to 33.1) for AAV: 15.4 (95\% CI 13.3 to 17.6) for GPA, 12.8 (95\% CI 10.8 to 14.8) for MPA and 1.8 (95\% CI 1.1 to 2.6) for eosinophilic GPA (EGPA). Incidence was stable during the study period, 30.3/million 1997–2003, 30.4/million 2004–2011 and 29.5/million 2012–2019. The incidence increased with age and was highest in age group 70–84 years (96/million adults). On 1 January 2020, the prevalence was 428/million adults and was higher in males than in females (480 vs 378/million).
Conclusions The incidence of AAV in southern Sweden was found stable over the course of 23 years; while the prevalence has increased, which might indicate better management and treatment of AAV resulting in improved survival.},
	language = {en},
	number = {1},
	urldate = {2023-04-06},
	journal = {RMD Open},
	publisher = {BMJ Specialist Journals},
	author = {Rathmann, Jens and Segelmark, Mårten and Englund, Martin and Mohammad, Aladdin J.},
	month = mar,
	year = {2023},
	note = {Number: 1},
	keywords = {Epidemiology, Granulomatosis with polyangiitis, Systemic vasculitis},
	pages = {e002949},
}

Objective To update the epidemiology of anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) in a defined geographical area of southern Sweden. Methods The study area comprised 14 municipalities with a combined adult population (≥18 years) of 623 872 in 2019. All cases diagnosed with AAV in 1997–2019 in the study area were included in the estimate of incidence. Diagnosis of AAV was verified by case record review, and cases were classified using the European Medicines Agency algorithm. Point prevalence was estimated on 01 January 2020. Results Three hundred and seventy-four patients (median age 67.5 years, 47% female) were diagnosed with new-onset AAV during the study period. One hundred and ninety-two were classified as granulomatosis with polyangiitis (GPA), 159 as microscopic polyangiitis (MPA) and 23 as EGPA. The average annual incidence/million adults was 30.1 (95% CI 27.0 to 33.1) for AAV: 15.4 (95% CI 13.3 to 17.6) for GPA, 12.8 (95% CI 10.8 to 14.8) for MPA and 1.8 (95% CI 1.1 to 2.6) for eosinophilic GPA (EGPA). Incidence was stable during the study period, 30.3/million 1997–2003, 30.4/million 2004–2011 and 29.5/million 2012–2019. The incidence increased with age and was highest in age group 70–84 years (96/million adults). On 1 January 2020, the prevalence was 428/million adults and was higher in males than in females (480 vs 378/million). Conclusions The incidence of AAV in southern Sweden was found stable over the course of 23 years; while the prevalence has increased, which might indicate better management and treatment of AAV resulting in improved survival.

@article{gong_association_2023,
	chapter = {Article},
	title = {The association between quadriceps strength and synovitis in knee osteoarthritis: an exploratory study from the {Osteoarthritis} {Initiative}},
	volume = {50},
	copyright = {© 2023 The Journal of Rheumatology},
	issn = {0315-162X, 1499-2752},
	shorttitle = {The association between quadriceps strength and synovitis in knee osteoarthritis},
	url = {https://www.jrheum.org/content/early/2023/01/25/jrheum.220538},
	doi = {10.3899/jrheum.220538},
	abstract = {Objective The aim of this study was to explore the association between quadriceps strength and synovitis in knee osteoarthritis (KOA).
Methods This study was derived from the Osteoarthritis Initiative (OAI), which recruited adults from the OAI cohort with or at risk of KOA. Knees with complete records of isometric quadriceps strength and effusion-synovitis and Hoffa-synovitis assessments were included. Quadriceps strength was measured isometrically at baseline. Effusion-synovitis and Hoffa-synovitis were measured using the Magnetic Resonance Imaging Osteoarthritis Knee Score at baseline and at 1-year and 2-year follow-ups. Generalized estimating equations were used to analyze the associations of baseline quadriceps strength with changes in effusion-synovitis and Hoffa-synovitis in multivariable analyses. Additionally, analyses were stratified by synovitis-driven inflammatory phenotypes.
Results A total of 1513 knees were included in this study. In total, 61\% of the subjects were female; subjects had an average age of 61.9 (SD 8.8) years and a mean BMI of 29.4 (SD 4.7). Regarding the whole population, baseline quadriceps strength was negatively associated with baseline effusion-synovitis and follow-up changes in effusion-synovitis (odds ratio [OR] 0.77-0.86), but no significant association was observed in terms of Hoffa-synovitis. Stratified by synovitis-driven inflammatory phenotype, baseline quadriceps strength was significantly associated with follow-up changes in effusion-synovitis—but not in Hoffa-synovitis—in the population with existing effusion-synovitis (OR 0.75-0.79).
Conclusion Higher baseline quadriceps strength was negatively associated with changes in effusion-synovitis—but not in Hoffa-synovitis—especially in the population with existing effusion-synovitis. Our findings suggested a potential protective role of the quadriceps in effusion-synovitis.},
	language = {en},
	number = {4},
	urldate = {2023-02-02},
	journal = {The Journal of Rheumatology},
	publisher = {The Journal of Rheumatology},
	author = {Gong, Ze and Li, Shengfa and Cao, Peihua and Ruan, Guangfeng and Zhang, Yan and Zeng, Qing and He, Zijun and Li, Shilin and Chen, Rong and Zheng, Peng and Fan, Tao and Lu, Pengcheng and Zhao, Yijin and Englund, Martin and Madry, Henning and Huang, Guozhi and Li, Le and Li, Jia and Ding, Changhai},
	month = apr,
	year = {2023},
	note = {Number: 4},
	pages = {548--555},
}

Objective The aim of this study was to explore the association between quadriceps strength and synovitis in knee osteoarthritis (KOA). Methods This study was derived from the Osteoarthritis Initiative (OAI), which recruited adults from the OAI cohort with or at risk of KOA. Knees with complete records of isometric quadriceps strength and effusion-synovitis and Hoffa-synovitis assessments were included. Quadriceps strength was measured isometrically at baseline. Effusion-synovitis and Hoffa-synovitis were measured using the Magnetic Resonance Imaging Osteoarthritis Knee Score at baseline and at 1-year and 2-year follow-ups. Generalized estimating equations were used to analyze the associations of baseline quadriceps strength with changes in effusion-synovitis and Hoffa-synovitis in multivariable analyses. Additionally, analyses were stratified by synovitis-driven inflammatory phenotypes. Results A total of 1513 knees were included in this study. In total, 61% of the subjects were female; subjects had an average age of 61.9 (SD 8.8) years and a mean BMI of 29.4 (SD 4.7). Regarding the whole population, baseline quadriceps strength was negatively associated with baseline effusion-synovitis and follow-up changes in effusion-synovitis (odds ratio [OR] 0.77-0.86), but no significant association was observed in terms of Hoffa-synovitis. Stratified by synovitis-driven inflammatory phenotype, baseline quadriceps strength was significantly associated with follow-up changes in effusion-synovitis—but not in Hoffa-synovitis—in the population with existing effusion-synovitis (OR 0.75-0.79). Conclusion Higher baseline quadriceps strength was negatively associated with changes in effusion-synovitis—but not in Hoffa-synovitis—especially in the population with existing effusion-synovitis. Our findings suggested a potential protective role of the quadriceps in effusion-synovitis.

@article{magnusson_prevalence_2023,
	title = {Prevalence of long {COVID} complaints in persons with and without {COVID}-19},
	volume = {13},
	copyright = {2023 The Author(s)},
	issn = {2045-2322},
	url = {https://www.nature.com/articles/s41598-023-32636-y},
	doi = {10.1038/s41598-023-32636-y},
	abstract = {We studied the prevalence and patterns of typical long COVID complaints in {\textasciitilde} 2.3 million individuals aged 18–70 years with and without confirmed COVID-19 in a Nation-wide population-based prospective cohort study in Norway. Our main outcome measures were the period prevalence of single-occurring or different combinations of complaints based on medical records: (1) Pulmonary (dyspnea and/or cough), (2) Neurological (concentration problems, memory loss), and/or (3) General complaints (fatigue). In persons testing positive (n = 75 979), 64 (95\% confidence interval: 54 to 73) and 122 (111 to 113) more persons per 10 000 persons had pulmonary complaints 5–6 months after the test compared to 10 000 persons testing negative (n = 1 167 582) or untested (n = 1 084 578), respectively. The corresponding difference in prevalence of general complaints (fatigue) was 181 (168 to 195) and 224 (211 to 238) per 10 000, and of neurological complaints 5 (2 to 8) and 9 (6–13) per 10 000. Overlap between complaints was rare. Long COVID complaints were only slightly more prevalent in persons with than without confirmed COVID-19. Still, long COVID may pose a substantial burden to healthcare systems in the future given the lasting high incidence of symptomatic COVID-19 in both vaccinated and unvaccinated individuals.},
	language = {en},
	number = {1},
	urldate = {2023-04-18},
	journal = {Scientific Reports},
	publisher = {Nature Publishing Group},
	author = {Magnusson, Karin and Turkiewicz, Aleksandra and Flottorp, Signe Agnes and Englund, Martin},
	month = apr,
	year = {2023},
	note = {Number: 1},
	keywords = {Epidemiology, Fatigue, Immunology, Infectious diseases, Public health, Signs and symptoms, Viral infection},
	pages = {6074},
}

We studied the prevalence and patterns of typical long COVID complaints in ~ 2.3 million individuals aged 18–70 years with and without confirmed COVID-19 in a Nation-wide population-based prospective cohort study in Norway. Our main outcome measures were the period prevalence of single-occurring or different combinations of complaints based on medical records: (1) Pulmonary (dyspnea and/or cough), (2) Neurological (concentration problems, memory loss), and/or (3) General complaints (fatigue). In persons testing positive (n = 75 979), 64 (95% confidence interval: 54 to 73) and 122 (111 to 113) more persons per 10 000 persons had pulmonary complaints 5–6 months after the test compared to 10 000 persons testing negative (n = 1 167 582) or untested (n = 1 084 578), respectively. The corresponding difference in prevalence of general complaints (fatigue) was 181 (168 to 195) and 224 (211 to 238) per 10 000, and of neurological complaints 5 (2 to 8) and 9 (6–13) per 10 000. Overlap between complaints was rare. Long COVID complaints were only slightly more prevalent in persons with than without confirmed COVID-19. Still, long COVID may pose a substantial burden to healthcare systems in the future given the lasting high incidence of symptomatic COVID-19 in both vaccinated and unvaccinated individuals.

@article{englund_pain_2023,
	title = {Pain in clinical trials for knee osteoarthritis: estimation of regression to the mean},
	volume = {5},
	issn = {2665-9913},
	shorttitle = {Pain in clinical trials for knee osteoarthritis},
	url = {https://www.thelancet.com/journals/lanrhe/article/PIIS2665-9913(23)00090-5/fulltext},
	doi = {10.1016/S2665-9913(23)00090-5},
	language = {English},
	number = {6},
	urldate = {2023-05-12},
	journal = {The Lancet Rheumatology},
	publisher = {Elsevier},
	author = {Englund, Martin and Turkiewicz, Aleksandra},
	month = apr,
	year = {2023},
	note = {Number: 6},
	pages = {E309--E311},
}

@article{dellisola_identifying_2023,
	title = {Identifying non-steroidal anti-inflammatory drug ({NSAID}) users among people with osteoarthritis through administrative and clinician-reported data - {A} validation study of 116,162 patients},
	volume = {15},
	issn = {1179-1349},
	doi = {10.2147/CLEP.S401726},
	abstract = {PURPOSE: (i) To report the prevalence of participants to a first-line intervention for OA in Sweden using over-the-counter (OTC) and/or prescribed NSAIDs; (ii) To estimate the accuracy of dispensed prescriptions of NSAIDs recorded in a Swedish health-care register to capture the use of NSAID considering clinician-report as reference standard.
METHODS: Register-based study. We used data from OA individuals who participated in the Swedish first-line intervention recorded in the Swedish Osteoarthritis Register (SOAR). SOAR includes clinician-reported use of NSAIDs in the three months preceding the intervention. We used the Prescribed Drug Register to retrieve data on NSAID prescriptions dispensed in the same period. We estimated the prevalence of OTC users (individuals with clinicians-reported use of NSAID but no prescription dispensed), prescription users (individuals with clinicians-reported use of NSAID and a prescription dispensed) and non-users (neither of the previous). We calculated sensitivity, specificity, positive predictive value, and negative predictive value of dispensed prescriptions of NSAIDs vs clinician-report.
RESULTS: We included 116,162 individuals (mean age [Standard Deviation]: 66 [9.6] years, 79\% women, 77\% knee OA). Overall, 24.7\% (95\% Confidence Intervals [CI] 24.5\%; 25.0\%) used OTC NSAIDs only, 18.2\% (18.0\%; 18.5\%) used prescribed NSAIDs, 6.6\% (6-4\%; 6.7\%) reported not using NSAIDs while having an NSAID prescription dispensed. Of the 49,913 individuals with clinician-reported use of NSAIDs, 21,190 had a prescription dispensed (sensitivity: 42.5\% [95\% CI 42.0\%, 42.9\%]; positive predictive value: 73.5\% [73.0\%, 74.0\%]). Of the 66,249 individuals reporting not using NSAIDs, 58,617 did not have a prescription dispensed (specificity: 88.5\% [88.2\%, 88.7\%]; negative predictive value: 67.1\% [66.8\%, 67.4\%]).
CONCLUSION: Overall, 24.7\% of participants in a first-line intervention for OA used OTC NSAIDs only while 18.2\% used prescribed NSAIDs. Dispensed prescriptions of NSAIDs have high specificity but low sensitivity and can correctly identify about 70\% of both the non-users and users in this population.},
	language = {eng},
	journal = {Clinical Epidemiology},
	author = {Dell'Isola, Andrea and Kiadaliri, Ali and Hellberg, Clara and Turkiewicz, Aleksandra and Englund, Martin},
	month = jun,
	year = {2023},
	keywords = {NSAID, osteoarthritis, register, validation},
	pages = {743--752},
}

PURPOSE: (i) To report the prevalence of participants to a first-line intervention for OA in Sweden using over-the-counter (OTC) and/or prescribed NSAIDs; (ii) To estimate the accuracy of dispensed prescriptions of NSAIDs recorded in a Swedish health-care register to capture the use of NSAID considering clinician-report as reference standard. METHODS: Register-based study. We used data from OA individuals who participated in the Swedish first-line intervention recorded in the Swedish Osteoarthritis Register (SOAR). SOAR includes clinician-reported use of NSAIDs in the three months preceding the intervention. We used the Prescribed Drug Register to retrieve data on NSAID prescriptions dispensed in the same period. We estimated the prevalence of OTC users (individuals with clinicians-reported use of NSAID but no prescription dispensed), prescription users (individuals with clinicians-reported use of NSAID and a prescription dispensed) and non-users (neither of the previous). We calculated sensitivity, specificity, positive predictive value, and negative predictive value of dispensed prescriptions of NSAIDs vs clinician-report. RESULTS: We included 116,162 individuals (mean age [Standard Deviation]: 66 [9.6] years, 79% women, 77% knee OA). Overall, 24.7% (95% Confidence Intervals [CI] 24.5%; 25.0%) used OTC NSAIDs only, 18.2% (18.0%; 18.5%) used prescribed NSAIDs, 6.6% (6-4%; 6.7%) reported not using NSAIDs while having an NSAID prescription dispensed. Of the 49,913 individuals with clinician-reported use of NSAIDs, 21,190 had a prescription dispensed (sensitivity: 42.5% [95% CI 42.0%, 42.9%]; positive predictive value: 73.5% [73.0%, 74.0%]). Of the 66,249 individuals reporting not using NSAIDs, 58,617 did not have a prescription dispensed (specificity: 88.5% [88.2%, 88.7%]; negative predictive value: 67.1% [66.8%, 67.4%]). CONCLUSION: Overall, 24.7% of participants in a first-line intervention for OA used OTC NSAIDs only while 18.2% used prescribed NSAIDs. Dispensed prescriptions of NSAIDs have high specificity but low sensitivity and can correctly identify about 70% of both the non-users and users in this population.

@article{iwarsson_proactive_2023,
	title = {‘{Proactive} aging’ is a new research approach for a new era},
	volume = {3},
	copyright = {2023 The Author(s), under exclusive licence to Springer Nature America, Inc.},
	issn = {2662-8465},
	url = {https://www.nature.com/articles/s43587-023-00438-6},
	doi = {10.1038/s43587-023-00438-6},
	language = {en},
	number = {7},
	urldate = {2024-08-28},
	journal = {Nature Aging},
	publisher = {Nature Publishing Group},
	author = {Iwarsson, Susanne and Jönson, Håkan and Deierborg, Tomas and Ehinger, Johannes K. and Hansson, Oskar and Isaksson, Hanna and Englund, Martin},
	month = jul,
	year = {2023},
	keywords = {Medical research, Molecular biology, Neuroscience, Social sciences},
	pages = {755--756},
}

@article{nagel_reduced_2023,
	title = {Reduced risk of serious pneumococcal infections up to 10 years after a dose of pneumococcal conjugate vaccine in established arthritis},
	volume = {41},
	issn = {1873-2518},
	doi = {10.1016/j.vaccine.2022.11.075},
	abstract = {BACKGROUND: To examine rates of serious pneumococcal infections up to 10 years after vaccination with 7-valent conjugated pneumococcal vaccine (PCV7) in patients with arthritis compared to non-vaccinated arthritis patients.
METHODS: In total, 595 adult arthritis patients (rheumatoid arthritis; RA = 342, 80 \% women and spondylarthropathy; SpA = 253, 45 \% women) received one dose of PCV7. Mean age/disease duration were 62/16 and 51/14 years, respectively. For each patient, 4 matched reference subjects were identified. At vaccination, 420 patients received bDMARDs (anti-TNF = 330, tocilizumab = 15, abatacept = 18, anakinra = 1, rituximab = 56). Methotrexate was given as monotherapy (n = 86) or in combination with bDMARD (n = 220). 89 SpA patients received NSAIDs without DMARD. The Skåne Healthcare Register was searched for ICD-10 diagnostic codes for pneumococcal infections (pneumonia, lower respiratory tract infection, septicemia, meningitis, septic arthritis) between January 2000 and December 2018. Frequency of infections after vs before vaccination were calculated (relative risks). Relative risk ratio (RRR) and relative risk reduction (1-RRR) were calculated comparing patients vs non-vaccinated references. Kaplan-Meier and Cox regression were used to investigate time to first event and predictors of infections.
RESULTS: Among vaccinated RA and SpA patients, there was a significant relative risk reduction of pneumonia and all serious infections; 53\% and 46\%, respectively. There was no significant difference in time to first pneumonia or all serious infections after vaccination between patients and references. Higher age, RA diagnosis and concomitant prednisolone were associated with infections.
CONCLUSION: One dose of pneumococcal conjugate vaccine may decrease risk of serious pneumococcal infection up to 10 years in patients with arthritis receiving immunomodulating treatment.},
	language = {eng},
	number = {2},
	journal = {Vaccine},
	author = {Nagel, J. and Jönsson, G. and Nilsson, J.-Å and Manuswin, C. and Englund, M. and Saxne, T. and Kapetanovic, M. C.},
	month = jan,
	year = {2023},
	keywords = {Adult, Antirheumatic Agents, Arthritis, Rheumatoid, Conjugated pneumococcal vaccine, Female, Humans, Inflammatory arthritis, Male, Pneumococcal Infections, Pneumococcal Vaccines, Pneumococcal infection, Tumor Necrosis Factor Inhibitors, Vaccine efficacy, Vaccines, Conjugate},
	pages = {504--510},
}

BACKGROUND: To examine rates of serious pneumococcal infections up to 10 years after vaccination with 7-valent conjugated pneumococcal vaccine (PCV7) in patients with arthritis compared to non-vaccinated arthritis patients. METHODS: In total, 595 adult arthritis patients (rheumatoid arthritis; RA = 342, 80 % women and spondylarthropathy; SpA = 253, 45 % women) received one dose of PCV7. Mean age/disease duration were 62/16 and 51/14 years, respectively. For each patient, 4 matched reference subjects were identified. At vaccination, 420 patients received bDMARDs (anti-TNF = 330, tocilizumab = 15, abatacept = 18, anakinra = 1, rituximab = 56). Methotrexate was given as monotherapy (n = 86) or in combination with bDMARD (n = 220). 89 SpA patients received NSAIDs without DMARD. The Skåne Healthcare Register was searched for ICD-10 diagnostic codes for pneumococcal infections (pneumonia, lower respiratory tract infection, septicemia, meningitis, septic arthritis) between January 2000 and December 2018. Frequency of infections after vs before vaccination were calculated (relative risks). Relative risk ratio (RRR) and relative risk reduction (1-RRR) were calculated comparing patients vs non-vaccinated references. Kaplan-Meier and Cox regression were used to investigate time to first event and predictors of infections. RESULTS: Among vaccinated RA and SpA patients, there was a significant relative risk reduction of pneumonia and all serious infections; 53% and 46%, respectively. There was no significant difference in time to first pneumonia or all serious infections after vaccination between patients and references. Higher age, RA diagnosis and concomitant prednisolone were associated with infections. CONCLUSION: One dose of pneumococcal conjugate vaccine may decrease risk of serious pneumococcal infection up to 10 years in patients with arthritis receiving immunomodulating treatment.

@article{hellberg_3d_2023,
	title = {{3D} analysis and grading of calcifications from ex vivo human meniscus},
	volume = {31},
	issn = {1522-9653},
	doi = {10.1016/j.joca.2022.10.016},
	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).},
	language = {eng},
	number = {4},
	journal = {Osteoarthritis and Cartilage},
	author = {Hellberg, I. and Karjalainen, V.-P. and Finnilä, M. a. J. and Jonsson, E. and Turkiewicz, A. and Önnerfjord, P. and Hughes, V. and Tjörnstrand, J. and Englund, M. and Saarakkala, S.},
	month = apr,
	year = {2023},
	keywords = {Calcification grading, Calcinosis, Humans, Magnetic Resonance Imaging, Meniscal calcification, Menisci, Tibial, Meniscus, Micro-computed tomography, Osteoarthritis, Knee, Volumetric analysis, X-Ray Microtomography},
	pages = {482--492},
}

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).

@article{kamps_occurrence_2023,
	title = {Occurrence of comorbidity following osteoarthritis diagnosis: a cohort study in the {Netherlands}},
	volume = {31},
	issn = {1522-9653},
	shorttitle = {Occurrence of comorbidity following osteoarthritis diagnosis},
	doi = {10.1016/j.joca.2022.12.003},
	abstract = {OBJECTIVE: To determine the risk of comorbidity following diagnosis of knee or hip osteoarthritis (OA).
DESIGN: A cohort study was conducted using the Integrated Primary Care Information database, containing electronic health records of 2.5 million patients from the Netherlands. Adults at risk for OA were included. Diagnosis of knee or hip OA (=exposure) and 58 long-term comorbidities (=outcome) were defined by diagnostic codes following the International Classification of Primary Care coding system. Time between the start of follow-up and incident diagnosis of OA was defined as unexposed, and between diagnosis of OA and the end of follow-up as exposed. Age and sex adjusted hazard ratios (HRs) comparing comorbidity rates in exposed and unexposed patient time were estimated with 99.9\% confidence intervals (CI).
RESULTS: The study population consisted of 1,890,712 patients. For 30 of the 58 studied comorbidities, exposure to knee OA showed a HR larger than 1. Largest positive associations (HR with (99.9\% CIs)) were found for obesity 2.55 (2.29-2.84) and fibromyalgia 2.06 (1.53-2.77). For two conditions a HR {\textless} 1 was found, other comorbidities showed no association with exposure to knee OA. For 26 comorbidities, exposure to hip OA showed a HR larger than 1. The largest were found for polymyalgia rheumatica 1.81 (1.41-2.32) and fibromyalgia 1.70 (1.10-2.63). All other comorbidities showed no associations with hip OA.
CONCLUSION: This study showed that many comorbidities were diagnosed more often in patients with knee or hip OA. This suggests that the management of OA should consider the risk of other long-term-conditions.},
	language = {eng},
	number = {4},
	journal = {Osteoarthritis and Cartilage},
	author = {Kamps, A. and Runhaar, J. and de Ridder, M. a. J. and de Wilde, M. and van der Lei, J. and Zhang, W. and Prieto-Alhambra, D. and Englund, M. and de Schepper, E. I. T. and Bierma-Zeinstra, S. M. A.},
	month = apr,
	year = {2023},
	keywords = {Adult, Cohort Studies, Comorbidity, Electronic health record (EHR), Fibromyalgia, Humans, Netherlands, Osteoarthritis, Osteoarthritis, Hip, Osteoarthritis, Knee, Primary care},
	pages = {519--528},
}

OBJECTIVE: To determine the risk of comorbidity following diagnosis of knee or hip osteoarthritis (OA). DESIGN: A cohort study was conducted using the Integrated Primary Care Information database, containing electronic health records of 2.5 million patients from the Netherlands. Adults at risk for OA were included. Diagnosis of knee or hip OA (=exposure) and 58 long-term comorbidities (=outcome) were defined by diagnostic codes following the International Classification of Primary Care coding system. Time between the start of follow-up and incident diagnosis of OA was defined as unexposed, and between diagnosis of OA and the end of follow-up as exposed. Age and sex adjusted hazard ratios (HRs) comparing comorbidity rates in exposed and unexposed patient time were estimated with 99.9% confidence intervals (CI). RESULTS: The study population consisted of 1,890,712 patients. For 30 of the 58 studied comorbidities, exposure to knee OA showed a HR larger than 1. Largest positive associations (HR with (99.9% CIs)) were found for obesity 2.55 (2.29-2.84) and fibromyalgia 2.06 (1.53-2.77). For two conditions a HR \textless 1 was found, other comorbidities showed no association with exposure to knee OA. For 26 comorbidities, exposure to hip OA showed a HR larger than 1. The largest were found for polymyalgia rheumatica 1.81 (1.41-2.32) and fibromyalgia 1.70 (1.10-2.63). All other comorbidities showed no associations with hip OA. CONCLUSION: This study showed that many comorbidities were diagnosed more often in patients with knee or hip OA. This suggests that the management of OA should consider the risk of other long-term-conditions.

@article{thorlund_opioid_2023,
	title = {Opioid dispensing in relation to arthroscopic knee surgery in {Denmark} from 2006 to 2018},
	volume = {70},
	issn = {2245-1919},
	abstract = {INTRODUCTION: In the US, opioids are commonly prescribed after arthroscopic knee surgery. We aimed to investigate opioid dispensing in relation to arthroscopic knee surgeries from 2006 to 2018 in Denmark.
METHODS: In Danish registries, we identified patients (≥ 15 years old) having arthroscopic knee surgery (anterior cruciate ligament (ACL) reconstruction; meniscal surgery; cartilage resection; synovectomy and diagnostic arthroscopy) between 1 January 2006 and 31 December 2018 and opioid dispensing (oral morphine equivalents (OMEQ)) within seven days after discharge from surgery.
RESULTS: Among 218,940 patients, 15,263 (7\%) had an opioid dispensed within seven days after being discharged following surgery. The opioid dispensing incidence (per 1,000 persons/year) increased during the study period for all procedures. This trend was more pronounced for ACL reconstruction, which recorded an increase from 86 (95\% confidence interval (CI): 75-99) in 2006 to 278 (95\% CI: 255-301) in 2018, corresponding to 9\% and 28\% of ACL patients, respectively. In the same period, the average amount of opioids dispensed within the first seven days after discharge decreased (change: 70.0 OMEQ (95\% CI: 12.4-127.5)). Tramadol and oxycodone were the most commonly dispensed opioids.
CONCLUSION: About 7\% of patients had an opioid dispensed within the first seven days after discharge following arthroscopic knee surgery. The incidence of opioids dispensed increased for all investigated procedures from 2006 to 2018. In the same period, the average amount of opioids dispensed within the first seven days after discharge decreased.
FUNDING: None.
TRIAL REGISTRATION: Not relevant.},
	language = {eng},
	number = {9},
	journal = {Danish Medical Journal},
	author = {Thorlund, Jonas Bloch and Lundberg, Matilde and Petersen, Jindong Ding and Englund, Martin and Viberg, Bjarke and Waldorff, Frans Boch and Søndergaard, Jens},
	month = aug,
	year = {2023},
	pages = {A01230032},
}

INTRODUCTION: In the US, opioids are commonly prescribed after arthroscopic knee surgery. We aimed to investigate opioid dispensing in relation to arthroscopic knee surgeries from 2006 to 2018 in Denmark. METHODS: In Danish registries, we identified patients (≥ 15 years old) having arthroscopic knee surgery (anterior cruciate ligament (ACL) reconstruction; meniscal surgery; cartilage resection; synovectomy and diagnostic arthroscopy) between 1 January 2006 and 31 December 2018 and opioid dispensing (oral morphine equivalents (OMEQ)) within seven days after discharge from surgery. RESULTS: Among 218,940 patients, 15,263 (7%) had an opioid dispensed within seven days after being discharged following surgery. The opioid dispensing incidence (per 1,000 persons/year) increased during the study period for all procedures. This trend was more pronounced for ACL reconstruction, which recorded an increase from 86 (95% confidence interval (CI): 75-99) in 2006 to 278 (95% CI: 255-301) in 2018, corresponding to 9% and 28% of ACL patients, respectively. In the same period, the average amount of opioids dispensed within the first seven days after discharge decreased (change: 70.0 OMEQ (95% CI: 12.4-127.5)). Tramadol and oxycodone were the most commonly dispensed opioids. CONCLUSION: About 7% of patients had an opioid dispensed within the first seven days after discharge following arthroscopic knee surgery. The incidence of opioids dispensed increased for all investigated procedures from 2006 to 2018. In the same period, the average amount of opioids dispensed within the first seven days after discharge decreased. FUNDING: None. TRIAL REGISTRATION: Not relevant.

@article{wijn_arthroscopic_2023,
	title = {Arthroscopic partial meniscectomy for the degenerative meniscus tear: a comparison of patients included in {RCTs} and prospective cohort studies},
	volume = {94},
	issn = {1745-3682},
	shorttitle = {Arthroscopic partial meniscectomy for the degenerative meniscus tear},
	doi = {10.2340/17453674.2023.24576},
	abstract = {BACKGROUND AND PURPOSE: Concerns exist regarding the generalizability of results from randomized controlled trials (RCTs) evaluating arthroscopic partial meniscectomy (APM) to treat degenerative meniscus tears. It has been suggested that study populations are not representative of subjects selected for surgery in daily clinical practice. Therefore, we aimed to compare patients included in trials and prospective cohort studies that received APM for a degenerative meniscus tear.
PATIENTS AND METHODS: Individual participant data from 4 RCTs and 2 cohort studies undergoing APM were collected. 1,970 patients were analyzed: 605 patients included in RCTs and 1,365 included in the cohorts. We compared patient and disease characteristics, knee pain, overall knee function, and health-related quality of life at baseline between the RCT and cohort groups using standardized differences, ratios comparing the variance of continuous covariates, and graphical methods such as quantile-quantile plots, side-by-side boxplots, and non-parametric density plots.
RESULTS: Differences between RCT and the cohort were observed primarily in age (younger patients in the cohort; standardized difference: 0.32) and disease severity, with the RCT group having more severe symptoms (standardized difference: 0.38). While knee pain, overall knee function, and quality of life generally showed minimal differences between the 2 groups, it is noteworthy that the largest observed difference was in knee pain, where the cohort group scored 7 points worse (95\% confidence interval 5-9, standardized difference: 0.29).
CONCLUSION: Patients in RCTs were largely representative of those in cohort studies regarding baseline scores, though variations in age and disease severity were observed. Younger patients with less severe osteoarthritis were more common in the cohort; however, trial participants still appear to be broadly representative of the target population.},
	language = {eng},
	journal = {Acta Orthopaedica},
	author = {Wijn, Stan R. W. and Hannink, Gerjon and Thorlund, Jonas B. and Sihvonen, Raine and Englund, Martin and Rovers, Maroeska M. and {meniscus IPDMA collaboration group}},
	month = nov,
	year = {2023},
	keywords = {Arthroscopy, Cohort Studies, Humans, Knee Joint, Meniscectomy, Menisci, Tibial, Meniscus, Osteoarthritis, Knee, Pain, Randomized Controlled Trials as Topic},
	pages = {570--576},
}

BACKGROUND AND PURPOSE: Concerns exist regarding the generalizability of results from randomized controlled trials (RCTs) evaluating arthroscopic partial meniscectomy (APM) to treat degenerative meniscus tears. It has been suggested that study populations are not representative of subjects selected for surgery in daily clinical practice. Therefore, we aimed to compare patients included in trials and prospective cohort studies that received APM for a degenerative meniscus tear. PATIENTS AND METHODS: Individual participant data from 4 RCTs and 2 cohort studies undergoing APM were collected. 1,970 patients were analyzed: 605 patients included in RCTs and 1,365 included in the cohorts. We compared patient and disease characteristics, knee pain, overall knee function, and health-related quality of life at baseline between the RCT and cohort groups using standardized differences, ratios comparing the variance of continuous covariates, and graphical methods such as quantile-quantile plots, side-by-side boxplots, and non-parametric density plots. RESULTS: Differences between RCT and the cohort were observed primarily in age (younger patients in the cohort; standardized difference: 0.32) and disease severity, with the RCT group having more severe symptoms (standardized difference: 0.38). While knee pain, overall knee function, and quality of life generally showed minimal differences between the 2 groups, it is noteworthy that the largest observed difference was in knee pain, where the cohort group scored 7 points worse (95% confidence interval 5-9, standardized difference: 0.29). CONCLUSION: Patients in RCTs were largely representative of those in cohort studies regarding baseline scores, though variations in age and disease severity were observed. Younger patients with less severe osteoarthritis were more common in the cohort; however, trial participants still appear to be broadly representative of the target population.

@article{clausen_two-year_2023,
	chapter = {Original research},
	title = {Two-year {MRI}-defined structural damage and patient-reported outcomes following surgery or exercise for meniscal tears in young adults},
	volume = {57},
	copyright = {© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.},
	issn = {0306-3674, 1473-0480},
	url = {https://bjsm.bmj.com/content/57/24/1566},
	doi = {10.1136/bjsports-2023-107352},
	abstract = {Objective To investigate potential differences in structural knee joint damage assessed by MRI and patient-reported outcomes (PROMs) at 2-year follow-up between young adults randomised to early surgery or exercise and education with optional delayed surgery for a meniscal tear.
Methods A secondary analysis of a multicentre randomised controlled trial including 121 patients (18–40 years) with an MRI-verified meniscal tear. For this study, only patients with 2-year follow-up were included. The main outcomes were the difference in worsening of structural knee damage, assessed by MRI using the Anterior Cruciate Ligament OsteoArthrits Score, and the difference in change in the mean score of four Knee Injury and Osteoarthritis Outcome Score (KOOS4) subscales covering pain, symptoms, function in sport and recreation, and quality of life, from baseline to 2 years.
Results In total, 82/121 (68\%) patients completed the 2-year follow-up (39 from the surgical group and 43 from the exercise group). MRI-defined cartilage damage had developed or progressed in seven (9.1\%) patients and osteophytes developed in two (2.6\%) patients. The worsening of structural damage from baseline to 2-year follow-up was similar between groups. The mean (95\% CI) adjusted differences in change in KOOS4 between intervention groups from baseline to 2 years was −1.4 (−9.1, 6.2) points. The mean improvement in KOOS4 was 16.4 (10.4, 22.4) in the surgical group and 21.5 (15.0, 28.0) in the exercise group. No between group differences in improvement were found in the KOOS subscales.
Conclusions The 2-year worsening of MRI-defined structural damage was limited and similar in young adult patients with a meniscal tear treated with surgery or exercise with optional delayed surgery. Both groups had similar clinically relevant improvements in KOOS4, suggesting the choice of treatment strategy does not impact 2-year structural knee damage or PROMs.
Trial registration number NCT02995551.},
	language = {en},
	number = {24},
	urldate = {2023-12-18},
	journal = {British Journal of Sports Medicine},
	publisher = {BMJ Publishing Group Ltd and British Association of Sport and Exercise Medicine},
	author = {Clausen, Stine Haugaard and Skou, Søren T. and Boesen, Mikael Ploug and Radev, Dimitar Ivanon and Kurt, Engin Yeter and Damsted, Camma and Hölmich, Per and Lind, Martin and Tørring, Sofus and Isaksen, Christin and Varnum, Claus and Englund, Martin and Thorlund, Jonas Bloch},
	month = dec,
	year = {2023},
	keywords = {Arthroscopy, Exercise Therapy, Meniscus, Osteoarthritis},
	pages = {1566--1572},
}

Objective To investigate potential differences in structural knee joint damage assessed by MRI and patient-reported outcomes (PROMs) at 2-year follow-up between young adults randomised to early surgery or exercise and education with optional delayed surgery for a meniscal tear. Methods A secondary analysis of a multicentre randomised controlled trial including 121 patients (18–40 years) with an MRI-verified meniscal tear. For this study, only patients with 2-year follow-up were included. The main outcomes were the difference in worsening of structural knee damage, assessed by MRI using the Anterior Cruciate Ligament OsteoArthrits Score, and the difference in change in the mean score of four Knee Injury and Osteoarthritis Outcome Score (KOOS4) subscales covering pain, symptoms, function in sport and recreation, and quality of life, from baseline to 2 years. Results In total, 82/121 (68%) patients completed the 2-year follow-up (39 from the surgical group and 43 from the exercise group). MRI-defined cartilage damage had developed or progressed in seven (9.1%) patients and osteophytes developed in two (2.6%) patients. The worsening of structural damage from baseline to 2-year follow-up was similar between groups. The mean (95% CI) adjusted differences in change in KOOS4 between intervention groups from baseline to 2 years was −1.4 (−9.1, 6.2) points. The mean improvement in KOOS4 was 16.4 (10.4, 22.4) in the surgical group and 21.5 (15.0, 28.0) in the exercise group. No between group differences in improvement were found in the KOOS subscales. Conclusions The 2-year worsening of MRI-defined structural damage was limited and similar in young adult patients with a meniscal tear treated with surgery or exercise with optional delayed surgery. Both groups had similar clinically relevant improvements in KOOS4, suggesting the choice of treatment strategy does not impact 2-year structural knee damage or PROMs. Trial registration number NCT02995551.

@article{dellisola_use_2023,
	chapter = {Osteoarthritis},
	title = {Use of non-surgical treatments on the journey to knee replacement in patients with knee osteoarthritis: a 10-year population-based case–control study},
	volume = {9},
	copyright = {© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.. http://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.},
	issn = {2056-5933},
	shorttitle = {Use of non-surgical treatments on the journey to knee replacement in patients with knee osteoarthritis},
	url = {https://rmdopen.bmj.com/content/9/3/e003422},
	doi = {10.1136/rmdopen-2023-003422},
	abstract = {Aim To investigate temporal trends in primary care visits, physiotherapy visits, dispensed non-steroidal anti-inflammatory drugs (NSAIDs) and opioids in knee osteoarthritis (OA) patients who have and have not undergone knee replacement.
Methods We analysed 5665 OA patients from the Skåne Healthcare Register, Sweden, who underwent knee replacement between 2015 and 2019. Controls were OA patients without knee replacement, matched 1:1 by sex, age, time and healthcare level of initial OA diagnosis, and assigned a pseudo-index date corresponding to their case’s knee replacement date. Annual prevalence and prevalence ratio of primary care and physiotherapy visits, dispensed NSAIDs and opioids (all for any cause) in the 10 years before knee replacement were estimated using Poisson regression.
Results The annual prevalence of all-cause primary care visits, physiotherapy visits and opioid use was similar between cases and controls until 3 years before the index date when it started to increase among the cases. The year before the index date, the prevalence ratio (cases vs controls) for physiotherapy use was 1.8 (95\% CI 1.7, 1.8), while for opioid use 1.6 (1.5, 1.7). NSAID use was consistently higher among cases, even 10 years before the index date when the prevalence ratio versus controls was 1.3 (1.2, 1.3), increasing to 1.8 (1.7, 1.9) in the year preceding the index date.
Conclusions Management of OA patients who have and have not undergone knee replacement appears largely similar except for higher use of NSAIDs in knee replacement cases. Symptomatic treatments start to increase a few years before the surgery in knee replacement cases.},
	language = {en},
	number = {3},
	urldate = {2023-10-02},
	journal = {RMD Open},
	publisher = {BMJ Specialist Journals},
	author = {Dell'Isola, Andrea and Hellberg, Clara and Turkiewicz, Aleksandra and Appleyard, Tom and Yu, Dahai and Thomas, Geraint and Peat, George and Englund, Martin},
	month = sep,
	year = {2023},
	keywords = {Epidemiology, Osteoarthritis, Knee, Rehabilitation},
	pages = {e003422},
}

Aim To investigate temporal trends in primary care visits, physiotherapy visits, dispensed non-steroidal anti-inflammatory drugs (NSAIDs) and opioids in knee osteoarthritis (OA) patients who have and have not undergone knee replacement. Methods We analysed 5665 OA patients from the Skåne Healthcare Register, Sweden, who underwent knee replacement between 2015 and 2019. Controls were OA patients without knee replacement, matched 1:1 by sex, age, time and healthcare level of initial OA diagnosis, and assigned a pseudo-index date corresponding to their case’s knee replacement date. Annual prevalence and prevalence ratio of primary care and physiotherapy visits, dispensed NSAIDs and opioids (all for any cause) in the 10 years before knee replacement were estimated using Poisson regression. Results The annual prevalence of all-cause primary care visits, physiotherapy visits and opioid use was similar between cases and controls until 3 years before the index date when it started to increase among the cases. The year before the index date, the prevalence ratio (cases vs controls) for physiotherapy use was 1.8 (95% CI 1.7, 1.8), while for opioid use 1.6 (1.5, 1.7). NSAID use was consistently higher among cases, even 10 years before the index date when the prevalence ratio versus controls was 1.3 (1.2, 1.3), increasing to 1.8 (1.7, 1.9) in the year preceding the index date. Conclusions Management of OA patients who have and have not undergone knee replacement appears largely similar except for higher use of NSAIDs in knee replacement cases. Symptomatic treatments start to increase a few years before the surgery in knee replacement cases.

@article{pineda-moncusi_classification_2023,
	title = {Classification of patients with osteoarthritis through clusters of comorbidities using 633 330 individuals from {Spain}},
	volume = {62},
	issn = {1462-0332},
	doi = {10.1093/rheumatology/kead038},
	abstract = {OBJECTIVES: To explore clustering of comorbidities among patients with a new diagnosis of OA and estimate the 10-year mortality risk for each identified cluster.
METHODS: This is a population-based cohort study of individuals with first incident diagnosis of OA of the hip, knee, ankle/foot, wrist/hand or 'unspecified' site between 2006 and 2020, using SIDIAP (a primary care database representative of Catalonia, Spain). At the time of OA diagnosis, conditions associated with OA in the literature that were found in ≥1\% of the individuals (n = 35) were fitted into two cluster algorithms, k-means and latent class analysis. Models were assessed using a range of internal and external evaluation procedures. Mortality risk of the obtained clusters was assessed by survival analysis using Cox proportional hazards.
RESULTS: We identified 633 330 patients with a diagnosis of OA. Our proposed best solution used latent class analysis to identify four clusters: 'low-morbidity' (relatively low number of comorbidities), 'back/neck pain plus mental health', 'metabolic syndrome' and 'multimorbidity' (higher prevalence of all studied comorbidities). Compared with the 'low-morbidity' cluster, the 'multimorbidity' cluster had the highest risk of 10-year mortality (adjusted hazard ratio [HR]: 2.19 [95\% CI: 2.15, 2.23]), followed by the 'metabolic syndrome' cluster (adjusted HR: 1.24 [95\% CI: 1.22, 1.27]) and the 'back/neck pain plus mental health' cluster (adjusted HR: 1.12 [95\% CI: 1.09, 1.15]).
CONCLUSION: Patients with a new diagnosis of OA can be clustered into groups based on their comorbidity profile, with significant differences in 10-year mortality risk. Further research is required to understand the interplay between OA and particular comorbidity groups, and the clinical significance of such results.},
	language = {eng},
	number = {11},
	journal = {Rheumatology (Oxford, England)},
	author = {Pineda-Moncusí, Marta and Dernie, Francesco and Dell'Isola, Andrea and Kamps, Anne and Runhaar, Jos and Swain, Subhashisa and Zhang, Weiya and Englund, Martin and Pitsillidou, Irene and Strauss, Victoria Y. and Robinson, Danielle E. and Prieto-Alhambra, Daniel and Khalid, Sara},
	month = nov,
	year = {2023},
	keywords = {Cohort Studies, Comorbidity, Humans, Neck Pain, OA, Osteoarthritis, Hip, Osteoarthritis, Knee, Spain, clustering, comorbidities, epidemiology},
	pages = {3592--3600},
}

OBJECTIVES: To explore clustering of comorbidities among patients with a new diagnosis of OA and estimate the 10-year mortality risk for each identified cluster. METHODS: This is a population-based cohort study of individuals with first incident diagnosis of OA of the hip, knee, ankle/foot, wrist/hand or 'unspecified' site between 2006 and 2020, using SIDIAP (a primary care database representative of Catalonia, Spain). At the time of OA diagnosis, conditions associated with OA in the literature that were found in ≥1% of the individuals (n = 35) were fitted into two cluster algorithms, k-means and latent class analysis. Models were assessed using a range of internal and external evaluation procedures. Mortality risk of the obtained clusters was assessed by survival analysis using Cox proportional hazards. RESULTS: We identified 633 330 patients with a diagnosis of OA. Our proposed best solution used latent class analysis to identify four clusters: 'low-morbidity' (relatively low number of comorbidities), 'back/neck pain plus mental health', 'metabolic syndrome' and 'multimorbidity' (higher prevalence of all studied comorbidities). Compared with the 'low-morbidity' cluster, the 'multimorbidity' cluster had the highest risk of 10-year mortality (adjusted hazard ratio [HR]: 2.19 [95% CI: 2.15, 2.23]), followed by the 'metabolic syndrome' cluster (adjusted HR: 1.24 [95% CI: 1.22, 1.27]) and the 'back/neck pain plus mental health' cluster (adjusted HR: 1.12 [95% CI: 1.09, 1.15]). CONCLUSION: Patients with a new diagnosis of OA can be clustered into groups based on their comorbidity profile, with significant differences in 10-year mortality risk. Further research is required to understand the interplay between OA and particular comorbidity groups, and the clinical significance of such results.

@article{diarbakerli_learning_2022,
	title = {Learning from the past to plan for the future: {A} scoping review of musculoskeletal clinical research in {Sweden} 2010–2020},
	volume = {127},
	copyright = {Copyright (c) 2022 Elias Diarbakerli, Olof Thoreson, Martin Björklund, Leif E. Dahlberg, Martin Englund, Paul Gerdhem, Joanna Kvist, Maziar  Mohaddes, Anneli Peolsson, Ola Rolfson, Birgitta  Öberg, Allan Abbott},
	issn = {2000-1967},
	shorttitle = {Learning from the past to plan for the future},
	url = {https://ujms.net/index.php/ujms/article/view/8709},
	doi = {10.48101/ujms.v127.8709},
	abstract = {Background: The aims of this study are to 1) determine the scope of musculoskeletal (MSK)-related clinical research in Sweden; 2) collate the amount of first-tier funding received; 3) discuss strategies and infrastructure supporting future MSK clinical trials in Sweden.
Methods: A systematic scoping review protocol was applied in PubMed, Scopus, and SweCRIS databases. The articles were examined, and data were extracted in multiple stages by three blinded authors.
Results: The search strategy resulted in 3,025 publications from 479 Swedish-affiliated authors. Primary health care was the basis for 14\% of the publications, 84\% from secondary health care, and 2\% from occupational health care with a similar proportional distribution of first-tier research grant financing. Approximately one in six publications were randomized controlled trials (RCTs), while the majority were of observational cohort design. The majority of publications in primary and occupational health care were related to pain disorders (51 and 67\%, respectively), especially diagnosis, prognosis, and healthcare organizational-related interventions (34\%) and rehabilitation (15\%) with similar proportional distribution of first-tier research grant financing. In secondary health care, rheumatic inflammatory disorder-related publications were most prevalent (30\%), most frequently concerning diagnosis, prognosis, and healthcare organizational-related interventions (20\%), attracting approximately half of all first-tier funding. Publications related to degenerative joint disorders (25\%), fractures (16\%), and joint, tendon, and muscle injuries (13\%) frequently concerned surgical and other orthopedic-related interventions (16, 6, and 8\%, respectively). Pain disorder-related publications (10\%) as well as bone health and osteoporosis-related publications (4\%) most frequently concerned diagnosis, prognosis, and healthcare organizational-related interventions (5 and 3\%, respectively).
Conclusions: Swedish-affiliated MSK disorder research 2010–2020 was predominantly observational cohort rather than RCT based. There was skewed first-tier funding allocation considering prevalence/incidence and burden of disease. Use of infrastructure supporting register-based RCTs, placebo-controlled RCTs, and hybrid effectiveness-implementation studies on prevention and clinical intervention is important strategies for the future in all healthcare sectors.},
	language = {en},
	urldate = {2022-11-22},
	journal = {Upsala Journal of Medical Sciences},
	author = {Diarbakerli, Elias and Thoreson, Olof and Björklund, Martin and Dahlberg, Leif E. and Englund, Martin and Gerdhem, Paul and Kvist, Joanna and Mohaddes, Maziar and Peolsson, Anneli and Rolfson, Ola and Öberg, Birgitta and Abbott, Allan},
	month = sep,
	year = {2022},
	keywords = {Musculoskeletal disorders, Sweden, clinical research, occupational health care, primary health care, research design, research funding, secondary health care},
}

Background: The aims of this study are to 1) determine the scope of musculoskeletal (MSK)-related clinical research in Sweden; 2) collate the amount of first-tier funding received; 3) discuss strategies and infrastructure supporting future MSK clinical trials in Sweden. Methods: A systematic scoping review protocol was applied in PubMed, Scopus, and SweCRIS databases. The articles were examined, and data were extracted in multiple stages by three blinded authors. Results: The search strategy resulted in 3,025 publications from 479 Swedish-affiliated authors. Primary health care was the basis for 14% of the publications, 84% from secondary health care, and 2% from occupational health care with a similar proportional distribution of first-tier research grant financing. Approximately one in six publications were randomized controlled trials (RCTs), while the majority were of observational cohort design. The majority of publications in primary and occupational health care were related to pain disorders (51 and 67%, respectively), especially diagnosis, prognosis, and healthcare organizational-related interventions (34%) and rehabilitation (15%) with similar proportional distribution of first-tier research grant financing. In secondary health care, rheumatic inflammatory disorder-related publications were most prevalent (30%), most frequently concerning diagnosis, prognosis, and healthcare organizational-related interventions (20%), attracting approximately half of all first-tier funding. Publications related to degenerative joint disorders (25%), fractures (16%), and joint, tendon, and muscle injuries (13%) frequently concerned surgical and other orthopedic-related interventions (16, 6, and 8%, respectively). Pain disorder-related publications (10%) as well as bone health and osteoporosis-related publications (4%) most frequently concerned diagnosis, prognosis, and healthcare organizational-related interventions (5 and 3%, respectively). Conclusions: Swedish-affiliated MSK disorder research 2010–2020 was predominantly observational cohort rather than RCT based. There was skewed first-tier funding allocation considering prevalence/incidence and burden of disease. Use of infrastructure supporting register-based RCTs, placebo-controlled RCTs, and hybrid effectiveness-implementation studies on prevention and clinical intervention is important strategies for the future in all healthcare sectors.

@article{yu_opioid_2022,
	title = {Opioid use prior to total knee replacement: comparative analysis of trends in {England} and {Sweden}},
	volume = {30},
	issn = {1063-4584, 1522-9653},
	shorttitle = {Opioid use prior to total knee replacement},
	url = {https://www.oarsijournal.com/article/S1063-4584(22)00687-2/fulltext},
	doi = {10.1016/j.joca.2022.02.621},
	language = {English},
	number = {6},
	urldate = {2023-09-12},
	journal = {Osteoarthritis and Cartilage},
	publisher = {Elsevier},
	author = {Yu, D. and Hellberg, C. and Appleyard, T. and Dell'Isola, A. and Thomas, G. E. R. and Turkiewicz, A. and Englund, M. and Peat, G.},
	month = jun,
	year = {2022},
	keywords = {Electronic health care record, Opioid, Total knee replacement},
	pages = {815--822},
}

@article{kiadaliri_gout_2022,
	chapter = {Gout},
	title = {Gout and hospital admission for ambulatory care–sensitive conditions: {Risks} and trajectories},
	volume = {49},
	copyright = {Copyright © 2022 by the Journal of Rheumatology},
	issn = {0315-162X, 1499-2752},
	shorttitle = {Gout and {Hospital} {Admission} for {Ambulatory} {Care}–{Sensitive} {Conditions}},
	url = {https://www.jrheum.org/content/49/7/731},
	doi = {10.3899/jrheum.220038},
	abstract = {Objective. To investigate the risks and trajectories of hospital admission for ambulatory care–sensitive conditions (ACSCs) in gout.
Methods. Among individuals aged 35 years to 85 years residing in Skåne, Sweden, in 2005, those with no doctor-diagnosed gout during 1998 to 2005 (n = 576,659) were followed from January 1, 2006, until a hospital admission for an ACSC, death, relocation outside Skåne, or December 31, 2016. Treating a new gout diagnosis (International Classification of Diseases, 10th revision, code M10) as a time-varying exposure, we used Cox proportional and additive hazard models to estimate the effects of gout on hospital admissions for ACSCs. We investigated the trajectory of hospital admissions for ACSCs from 3 years before to 3 years after gout diagnosis using generalized estimating equations and group-based trajectory modeling in an age-and sex-matched cohort study.
Results. Gout was associated with a 41\% increased rate of hospital admission for ACSCs (hazard ratio 1.41, 95\% CI 1.35-1.47), corresponding to 121 (95\% CI 104-138) more hospital admissions for ACSCs per 10,000 person-years compared with those without gout. Our trajectory analysis showed that higher rates of hospital admission for ACSCs among persons with gout were observed from 3 years before to 3 years after diagnosis, with the highest prevalence rate ratio (2.22, 95\% CI 1.92-2.53) at the 3-month period after diagnosis. We identified 3 classes with distinct trajectories of hospital admissions for ACSCs among patients with gout: almost none (88.5\%), low-rising (9.7\%), and moderate-sharply rising (1.8\%). The Charlson Comorbidity Index was the most important predictor of trajectory class membership.
Conclusion. Increased risk of hospital admissions for ACSCs in gout highlights the need for better management of the disease through outpatient care, especially among foreign-born, older patients with comorbidities.},
	language = {en},
	number = {7},
	urldate = {2023-08-29},
	journal = {The Journal of Rheumatology},
	publisher = {The Journal of Rheumatology},
	author = {Kiadaliri, Ali and Neogi, Tuhina and Englund, Martin},
	month = jul,
	year = {2022},
	keywords = {ambulatory care, gout, heterogeneity, hospitalization, longitudinal study, population registers},
	pages = {731--739},
}

Objective. To investigate the risks and trajectories of hospital admission for ambulatory care–sensitive conditions (ACSCs) in gout. Methods. Among individuals aged 35 years to 85 years residing in Skåne, Sweden, in 2005, those with no doctor-diagnosed gout during 1998 to 2005 (n = 576,659) were followed from January 1, 2006, until a hospital admission for an ACSC, death, relocation outside Skåne, or December 31, 2016. Treating a new gout diagnosis (International Classification of Diseases, 10th revision, code M10) as a time-varying exposure, we used Cox proportional and additive hazard models to estimate the effects of gout on hospital admissions for ACSCs. We investigated the trajectory of hospital admissions for ACSCs from 3 years before to 3 years after gout diagnosis using generalized estimating equations and group-based trajectory modeling in an age-and sex-matched cohort study. Results. Gout was associated with a 41% increased rate of hospital admission for ACSCs (hazard ratio 1.41, 95% CI 1.35-1.47), corresponding to 121 (95% CI 104-138) more hospital admissions for ACSCs per 10,000 person-years compared with those without gout. Our trajectory analysis showed that higher rates of hospital admission for ACSCs among persons with gout were observed from 3 years before to 3 years after diagnosis, with the highest prevalence rate ratio (2.22, 95% CI 1.92-2.53) at the 3-month period after diagnosis. We identified 3 classes with distinct trajectories of hospital admissions for ACSCs among patients with gout: almost none (88.5%), low-rising (9.7%), and moderate-sharply rising (1.8%). The Charlson Comorbidity Index was the most important predictor of trajectory class membership. Conclusion. Increased risk of hospital admissions for ACSCs in gout highlights the need for better management of the disease through outpatient care, especially among foreign-born, older patients with comorbidities.

@article{magnusson_genetic_2022,
	title = {The genetic contribution to hand osteoarthritis},
	volume = {30},
	issn = {1522-9653},
	doi = {10.1016/j.joca.2022.06.011},
	abstract = {OBJECTIVE: To estimate the genetic contribution to doctor-diagnosed hand osteoarthritis (OA).
METHODS: Using data from the Swedish Twin Registry and National Patient Register, we conducted a 20-year population-based longitudinal cohort study including 59,970 twins aged 35 years or older. We studied inpatient and outpatient doctor-diagnosed hand OA using ICD-10 codes from 1997 until 2016, including both the distal/proximal interphalangeal (DIP/PIP) joints and/or the first carpometacarpal (CMC-1) joints. We calculated intra-pair correlation, estimated the heritability (i.e., the percentage variation in hand OA that can be explained by genetic factors) as well as a genetic risk.
RESULTS: Among 59,970 included persons, 936 had a hand OA diagnosis registered during the study period. The heritabilities of hand OA (any joint), CMC-1 OA and DIP/PIP OA were ∼87\%, 86\% and 48\%, respectively, yet the two latter should be interpreted with care due to low numbers. Hand OA in any joint in both twins in a pair occurred more frequently in identical twins (54/554 = 9.7\%, intra-pair correlation = 0.54, 95\% CI = 0.44-0.63) than in fraternal twins (18/1,246 = 1.4\%, intra-pair correlation = 0.10, 95\% CI = -0.01-0.22). Identical twins who were diagnosed with hand OA in any joint had a far higher risk than fraternal twins with hand OA to also have their co-twin diagnosed with hand OA in any joint (Hazard Ratio = 6.98, 95\% CI = 3.08-15.45).
CONCLUSION: The genetic contribution to hand OA is high and likely varying between 48\% and 87\%. Potential differential heritability by hand OA phenotypes should be further explored.},
	language = {eng},
	number = {10},
	journal = {Osteoarthritis and Cartilage},
	author = {Magnusson, K. and Turkiewicz, A. and Haugen, I. K. and Englund, M.},
	month = oct,
	year = {2022},
	keywords = {Carpometacarpal Joints, Epidemiology, Genetics, Hand, Hand OA, Humans, Longitudinal Studies, Osteoarthritis, Twins, Dizygotic, Twins, Monozygotic},
	pages = {1385--1389},
}

OBJECTIVE: To estimate the genetic contribution to doctor-diagnosed hand osteoarthritis (OA). METHODS: Using data from the Swedish Twin Registry and National Patient Register, we conducted a 20-year population-based longitudinal cohort study including 59,970 twins aged 35 years or older. We studied inpatient and outpatient doctor-diagnosed hand OA using ICD-10 codes from 1997 until 2016, including both the distal/proximal interphalangeal (DIP/PIP) joints and/or the first carpometacarpal (CMC-1) joints. We calculated intra-pair correlation, estimated the heritability (i.e., the percentage variation in hand OA that can be explained by genetic factors) as well as a genetic risk. RESULTS: Among 59,970 included persons, 936 had a hand OA diagnosis registered during the study period. The heritabilities of hand OA (any joint), CMC-1 OA and DIP/PIP OA were ∼87%, 86% and 48%, respectively, yet the two latter should be interpreted with care due to low numbers. Hand OA in any joint in both twins in a pair occurred more frequently in identical twins (54/554 = 9.7%, intra-pair correlation = 0.54, 95% CI = 0.44-0.63) than in fraternal twins (18/1,246 = 1.4%, intra-pair correlation = 0.10, 95% CI = -0.01-0.22). Identical twins who were diagnosed with hand OA in any joint had a far higher risk than fraternal twins with hand OA to also have their co-twin diagnosed with hand OA in any joint (Hazard Ratio = 6.98, 95% CI = 3.08-15.45). CONCLUSION: The genetic contribution to hand OA is high and likely varying between 48% and 87%. Potential differential heritability by hand OA phenotypes should be further explored.

@article{brown_clinical_2022,
	title = {Clinical versus {MRI} grading of the medial collateral ligament in acute knee injury},
	volume = {Epub},
	issn = {1543-8635},
	url = {https://doi.org/10.1080/15438627.2022.2079981},
	doi = {10.1080/15438627.2022.2079981},
	abstract = {Sensitivity, specificity, and agreement between clinical and magnetic resonance imaging (MRI) gradings of the medial collateral ligament (MCL) after acute knee injury were evaluated in 362 patients. Ninety-seven per cent were injured during sports/recreation. Sensitivity and specificity of MRI for grade II or III MCL injury was 68\% (95\% CI 58-77\%) and 90\% (95\% CI 86-93\%), respectively. Weighted Kappa analysis showed moderate agreement between clinical and MRI grading (0.56 [95\% CI 0.48-0.65]). Findings were similar for patients with and without concomitant cruciate ligament rupture (0.57 [95\% CI 0.48-0.66] and 0.55 [95\% CI 0.35-0.75], respectively) and for specialists in orthopaedics and knee sub-specialists (0.55 [95\% CI 0.39-0.70] and 0.57 [95\% CI 0.47-0.67], respectively). Agreement between clinical and MRI grading of MCL injuries by orthopaedic specialists in a general hospital is at least moderate regardless of the presence of cruciate ligament injury.},
	language = {eng},
	journal = {Research in Sports Medicine},
	author = {Brown, Jamie S. and Olsson, Ola and Isacsson, Anders and Englund, Martin},
	month = may,
	year = {2022},
	keywords = {Medial collateral ligament injury, clinical examination, magnetic resonance imaging},
	pages = {1--5},
}

Sensitivity, specificity, and agreement between clinical and magnetic resonance imaging (MRI) gradings of the medial collateral ligament (MCL) after acute knee injury were evaluated in 362 patients. Ninety-seven per cent were injured during sports/recreation. Sensitivity and specificity of MRI for grade II or III MCL injury was 68% (95% CI 58-77%) and 90% (95% CI 86-93%), respectively. Weighted Kappa analysis showed moderate agreement between clinical and MRI grading (0.56 [95% CI 0.48-0.65]). Findings were similar for patients with and without concomitant cruciate ligament rupture (0.57 [95% CI 0.48-0.66] and 0.55 [95% CI 0.35-0.75], respectively) and for specialists in orthopaedics and knee sub-specialists (0.55 [95% CI 0.39-0.70] and 0.57 [95% CI 0.47-0.67], respectively). Agreement between clinical and MRI grading of MCL injuries by orthopaedic specialists in a general hospital is at least moderate regardless of the presence of cruciate ligament injury.

@article{johansson_chronic_2022,
	title = {Chronic opioid use before and after exercise therapy and patient education among patients with knee or hip osteoarthritis},
	volume = {30},
	issn = {1522-9653},
	doi = {10.1016/j.joca.2022.08.001},
	abstract = {OBJECTIVE: To investigate changes in opioid use after supervised exercise therapy and patient education among knee or hip osteoarthritis patients with chronic opioid use.
METHOD: In this cohort study, we linked data from the Good Life with osteoArthritis in Denmark register (GLA:D®; standardised treatment program for osteoarthritis; January 2013 to November 2018) with national health registries. Among 35,549 patients, 1,262 were classified as chronic opioid users based on amount and temporal distribution of dispensed opioids the year before the intervention. We investigated changes in opioid use, measured as mg oral morphine equivalents (OMEQs), from the year before the intervention to the year after using generalized estimating equations.
RESULTS: We found a 10\% decrease in mg OMEQs from the year before to the year after the intervention (incidence rate ratio [IRR]: 0.90, 95\% confidence interval [CI]: 0.86, 0.94). Additional analyses suggested this decrease to be mainly attributable to regulatory actions targeting opioid prescribing during the study period (IRR among patients participating in the intervention before: 0.98 [95\% CI: 0.89, 1.07] vs after: 0.83 [0.74, 0.93] regulatory actions). In a random general population sample of matched chronic opioid users, a similar opioid use pattern was observed over time, further supporting the impact of regulatory actions on the opioid use in the study population.
CONCLUSION: Among patients with knee or hip osteoarthritis and chronic opioid use, a standardised treatment program did not change opioid use when regulatory changes in opioid prescribing were taken into account.},
	language = {eng},
	number = {11},
	journal = {Osteoarthritis and Cartilage},
	author = {Johansson, M. S. and Pottegård, A. and Søndergaard, J. and Englund, M. and Grønne, D. T. and Skou, S. T. and Roos, E. M. and Thorlund, J. B.},
	month = nov,
	year = {2022},
	keywords = {Analgesics, Opioid, Chronic opioid use, Cohort Studies, Deprescribing, Exercise Therapy, Exercise therapy, Humans, Morphine Derivatives, Osteoarthritis, Osteoarthritis, Hip, Osteoarthritis, Knee, Patient Education as Topic, Patient education, Practice Patterns, Physicians'},
	pages = {1536--1544},
}

OBJECTIVE: To investigate changes in opioid use after supervised exercise therapy and patient education among knee or hip osteoarthritis patients with chronic opioid use. METHOD: In this cohort study, we linked data from the Good Life with osteoArthritis in Denmark register (GLA:D®; standardised treatment program for osteoarthritis; January 2013 to November 2018) with national health registries. Among 35,549 patients, 1,262 were classified as chronic opioid users based on amount and temporal distribution of dispensed opioids the year before the intervention. We investigated changes in opioid use, measured as mg oral morphine equivalents (OMEQs), from the year before the intervention to the year after using generalized estimating equations. RESULTS: We found a 10% decrease in mg OMEQs from the year before to the year after the intervention (incidence rate ratio [IRR]: 0.90, 95% confidence interval [CI]: 0.86, 0.94). Additional analyses suggested this decrease to be mainly attributable to regulatory actions targeting opioid prescribing during the study period (IRR among patients participating in the intervention before: 0.98 [95% CI: 0.89, 1.07] vs after: 0.83 [0.74, 0.93] regulatory actions). In a random general population sample of matched chronic opioid users, a similar opioid use pattern was observed over time, further supporting the impact of regulatory actions on the opioid use in the study population. CONCLUSION: Among patients with knee or hip osteoarthritis and chronic opioid use, a standardised treatment program did not change opioid use when regulatory changes in opioid prescribing were taken into account.

@article{filbay_evidence_2022,
	chapter = {Original research},
	title = {Evidence of {ACL} healing on {MRI} following {ACL} rupture treated with rehabilitation alone may be associated with better patient-reported outcomes: a secondary analysis from the {KANON} trial},
	volume = {57},
	copyright = {© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.. http://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.},
	issn = {0306-3674, 1473-0480},
	shorttitle = {Evidence of {ACL} healing on {MRI} following {ACL} rupture treated with rehabilitation alone may be associated with better patient-reported outcomes},
	url = {https://bjsm.bmj.com/content/early/2022/11/03/bjsports-2022-105473},
	doi = {10.1136/bjsports-2022-105473},
	abstract = {Objectives Evaluate the natural course of anterior cruciate ligament (ACL) healing on MRI within 5 years of acute ACL rupture and compare 2-year and 5-year outcomes based on healing status and treatment group.
Methods Secondary analysis of 120 Knee Anterior Cruciate Ligament Nonsurgical vs Surgical Treatment (KANON) trial participants randomised to rehabilitation and optional delayed ACL reconstruction (ACLR) or early ACLR and rehabilitation. ACL continuity on MRI (Anterior Cruciate Ligament OsteoArthritis Score 0–2) was considered evidence of ACL healing. Outcomes included Knee Injury and Osteoarthritis Outcome Score (KOOS), KOOS patient acceptable symptomatic state (PASS) and treatment failure criteria. Linear mixed models were used to estimate adjusted mean differences (95\% CIs) in patient-reported sport and recreational function (KOOS-Sport/Rec) and quality of life (KOOS-QOL) at 2 and 5 years, between participants with MRI evidence of ACL healing and those who had (1) no evidence of ACL healing, (2) delayed ACLR or (3) early ACLR.
Results MRI evidence of ACL healing at 2-year follow-up was observed in 16 of 54 (30\%, 95\% CI 19 to 43\%) participants randomised to optional delayed ACLR. Excluding participants who had delayed ACLR, 16 of 30 (53\%, 36–70\%) participants managed with rehabilitation-alone displayed MRI evidence of ACL healing. Two-year outcomes were better in the healed ACL group (n=16) compared with the non-healed (n=14) (mean difference (95\% CI) KOOS-Sport/Rec: 25.1 (8.6–41.5); KOOS-QOL: 27.5 (13.2–41.8)), delayed ACLR (n=24) (KOOS-Sport/Rec: 24.9 (10.2–39.6); KOOS-QOL: 18.1 (5.4–30.8)) and early ACLR (n=62) (KOOS-Sport/Rec: 17.4 (4.1–30.7); KOOS-QOL: 11.4 (0.0–22.9)) groups. Five-year KOOS-QOL was better in the healed versus non-healed group (25.3 (9.4–41.2)). Of participants with MRI evidence of ACL healing, 63–94\% met the PASS criteria for each KOOS subscale, compared with 29–61\% in the non-healed or reconstructed groups.
Conclusions MRI appearance of ACL healing after ACL rupture occurred in one in three adults randomised to initial rehabilitation and one in two who did not cross-over to delayed ACLR and was associated with favourable outcomes. The potential for spontaneous healing of the ACL to facilitate better clinical outcomes may be greater than previously considered.
Trial registration number ISRCTN84752559.},
	language = {en},
	number = {2},
	urldate = {2022-11-07},
	journal = {British Journal of Sports Medicine},
	publisher = {BMJ Publishing Group Ltd and British Association of Sport and Exercise Medicine},
	author = {Filbay, Stephanie Rose and Roemer, Frank W. and Lohmander, L. Stefan and Turkiewicz, Aleksandra and Roos, Ewa M. and Frobell, Richard and Englund, Martin},
	month = nov,
	year = {2022},
	note = {Number: 2},
	keywords = {Magnetic Resonance Imaging, anterior cruciate ligament, osteoarthritis, quality of life, rehabilitation},
	pages = {91--98},
}

Objectives Evaluate the natural course of anterior cruciate ligament (ACL) healing on MRI within 5 years of acute ACL rupture and compare 2-year and 5-year outcomes based on healing status and treatment group. Methods Secondary analysis of 120 Knee Anterior Cruciate Ligament Nonsurgical vs Surgical Treatment (KANON) trial participants randomised to rehabilitation and optional delayed ACL reconstruction (ACLR) or early ACLR and rehabilitation. ACL continuity on MRI (Anterior Cruciate Ligament OsteoArthritis Score 0–2) was considered evidence of ACL healing. Outcomes included Knee Injury and Osteoarthritis Outcome Score (KOOS), KOOS patient acceptable symptomatic state (PASS) and treatment failure criteria. Linear mixed models were used to estimate adjusted mean differences (95% CIs) in patient-reported sport and recreational function (KOOS-Sport/Rec) and quality of life (KOOS-QOL) at 2 and 5 years, between participants with MRI evidence of ACL healing and those who had (1) no evidence of ACL healing, (2) delayed ACLR or (3) early ACLR. Results MRI evidence of ACL healing at 2-year follow-up was observed in 16 of 54 (30%, 95% CI 19 to 43%) participants randomised to optional delayed ACLR. Excluding participants who had delayed ACLR, 16 of 30 (53%, 36–70%) participants managed with rehabilitation-alone displayed MRI evidence of ACL healing. Two-year outcomes were better in the healed ACL group (n=16) compared with the non-healed (n=14) (mean difference (95% CI) KOOS-Sport/Rec: 25.1 (8.6–41.5); KOOS-QOL: 27.5 (13.2–41.8)), delayed ACLR (n=24) (KOOS-Sport/Rec: 24.9 (10.2–39.6); KOOS-QOL: 18.1 (5.4–30.8)) and early ACLR (n=62) (KOOS-Sport/Rec: 17.4 (4.1–30.7); KOOS-QOL: 11.4 (0.0–22.9)) groups. Five-year KOOS-QOL was better in the healed versus non-healed group (25.3 (9.4–41.2)). Of participants with MRI evidence of ACL healing, 63–94% met the PASS criteria for each KOOS subscale, compared with 29–61% in the non-healed or reconstructed groups. Conclusions MRI appearance of ACL healing after ACL rupture occurred in one in three adults randomised to initial rehabilitation and one in two who did not cross-over to delayed ACLR and was associated with favourable outcomes. The potential for spontaneous healing of the ACL to facilitate better clinical outcomes may be greater than previously considered. Trial registration number ISRCTN84752559.

@article{magnusson_post-covid_2022,
	title = {Post-covid medical complaints following infection with {SARS}-{CoV}-2 {Omicron} vs {Delta} variants},
	volume = {13},
	copyright = {2022 The Author(s)},
	issn = {2041-1723},
	url = {https://www.nature.com/articles/s41467-022-35240-2},
	doi = {10.1038/s41467-022-35240-2},
	abstract = {The SARS-CoV-2 Omicron (B.1.1.529) variant has been associated with less severe acute disease, however, concerns remain as to whether long-term complaints persist to a similar extent as for earlier variants. Studying 1 323 145 persons aged 18-70 years living in Norway with and without SARS-CoV-2 infection in a prospective cohort study, we found that individuals infected with Omicron had a similar risk of post-covid complaints (fatigue, cough, heart palpitations, shortness of breath and anxiety/depression) as individuals infected with Delta (B.1.617.2), from 14 to up to 126 days after testing positive, both in the acute (14 to 29 days), sub-acute (30 to 89 days) and chronic post-covid (≥90 days) phases. However, at ≥90 days after testing positive, individuals infected with Omicron had a lower risk of having any complaint (43 (95\%CI = 14 to 72) fewer per 10,000), as well as a lower risk of musculoskeletal pain (23 (95\%CI = 2-43) fewer per 10,000) than individuals infected with Delta. Our findings suggest that the acute and sub-acute burden of post-covid complaints on health services is similar for Omicron and Delta. The chronic burden may be lower for Omicron vs Delta when considering musculoskeletal pain, but not when considering other typical post-covid complaints.},
	language = {en},
	number = {1},
	urldate = {2022-12-01},
	journal = {Nature Communications},
	publisher = {Nature Publishing Group},
	author = {Magnusson, Karin and Kristoffersen, Doris Tove and Dell’Isola, Andrea and Kiadaliri, Ali and Turkiewicz, Aleksandra and Runhaar, Jos and Bierma-Zeinstra, Sita and Englund, Martin and Magnus, Per Minor and Kinge, Jonas Minet},
	month = nov,
	year = {2022},
	note = {Number: 1},
	keywords = {Rehabilitation, SARS-CoV-2, Viral infection},
	pages = {7363},
}

The SARS-CoV-2 Omicron (B.1.1.529) variant has been associated with less severe acute disease, however, concerns remain as to whether long-term complaints persist to a similar extent as for earlier variants. Studying 1 323 145 persons aged 18-70 years living in Norway with and without SARS-CoV-2 infection in a prospective cohort study, we found that individuals infected with Omicron had a similar risk of post-covid complaints (fatigue, cough, heart palpitations, shortness of breath and anxiety/depression) as individuals infected with Delta (B.1.617.2), from 14 to up to 126 days after testing positive, both in the acute (14 to 29 days), sub-acute (30 to 89 days) and chronic post-covid (≥90 days) phases. However, at ≥90 days after testing positive, individuals infected with Omicron had a lower risk of having any complaint (43 (95%CI = 14 to 72) fewer per 10,000), as well as a lower risk of musculoskeletal pain (23 (95%CI = 2-43) fewer per 10,000) than individuals infected with Delta. Our findings suggest that the acute and sub-acute burden of post-covid complaints on health services is similar for Omicron and Delta. The chronic burden may be lower for Omicron vs Delta when considering musculoskeletal pain, but not when considering other typical post-covid complaints.

@article{kiadaliri_impact_2022,
	title = {Impact of the first wave of the {COVID}-19 pandemic on healthcare use in osteoarthritis: {A} population register-based study in {Sweden}},
	volume = {4},
	issn = {2665-9131},
	shorttitle = {Impact of the first wave of the {COVID}-19 pandemic on healthcare use in osteoarthritis},
	url = {https://www.sciencedirect.com/science/article/pii/S2665913122000206},
	doi = {10.1016/j.ocarto.2022.100252},
	abstract = {Objective
To investigate whether the first wave of the COVID-19 pandemic impacted healthcare consultations (HCC) and hospitalization among people with and without osteoarthritis (OA).
Methods
Using register data, we included individuals aged ≥35 years residing in Skåne region, Sweden, during 2009–2019 with (n ​= ​123,523) and without (n ​= ​552,412) a diagnosis of OA during January 1, 2009–December 31, 2019. We collected bi-weekly individual data on HCC/hospitalization between January and May for years 2017–2020. Treating the year 2020 as intervention and 2017–2019 as control as well as dividing data to pre– (January–February) and post–pandemic (March–May), we applied event study design to measure the dynamic effects of the COVID-19 pandemic on HCC/hospitalization. We used fixed-effect Poisson regressions for estimation and subgroup analyses by sex, age, and comorbidity were conducted among OA patients.
Results
The impact of the pandemic on healthcare use was evident from mid-March 2020 (34–45\%/12–25\% reductions in in-person HCC/hospitalization) among people with OA relative to 2017–2019. Smaller reductions were seen in those without OA with 25–34\%/8–16\% reductions in in-person HCC/hospitalization. On contrary, there were increases in remote HCC following the pandemic (5–25\% and 11–31\% in people with and without OA, respectively). Among persons with OA, there were variations in the pandemic's effects by sex, age and comorbidity.
Conclusion
Despite no lockdown in Sweden there were substantial reductions in in-person healthcare use during the first wave of COVID-19 pandemic with greater reductions among people with than without OA.},
	language = {en},
	number = {2},
	urldate = {2022-04-21},
	journal = {Osteoarthritis and Cartilage Open},
	author = {Kiadaliri, Ali and Magnusson, Karin and Turkiewicz, Aleksandra and Dell’Isola, Andrea and Runhaar, Jos and Bierma-Zeinstra, Sita and Englund, Martin},
	month = jun,
	year = {2022},
	note = {Number: 2},
	keywords = {Covid-19, Event-study design, Healthcare use, Osteoarthritis, Sweden},
	pages = {100252},
}

Objective To investigate whether the first wave of the COVID-19 pandemic impacted healthcare consultations (HCC) and hospitalization among people with and without osteoarthritis (OA). Methods Using register data, we included individuals aged ≥35 years residing in Skåne region, Sweden, during 2009–2019 with (n ​= ​123,523) and without (n ​= ​552,412) a diagnosis of OA during January 1, 2009–December 31, 2019. We collected bi-weekly individual data on HCC/hospitalization between January and May for years 2017–2020. Treating the year 2020 as intervention and 2017–2019 as control as well as dividing data to pre– (January–February) and post–pandemic (March–May), we applied event study design to measure the dynamic effects of the COVID-19 pandemic on HCC/hospitalization. We used fixed-effect Poisson regressions for estimation and subgroup analyses by sex, age, and comorbidity were conducted among OA patients. Results The impact of the pandemic on healthcare use was evident from mid-March 2020 (34–45%/12–25% reductions in in-person HCC/hospitalization) among people with OA relative to 2017–2019. Smaller reductions were seen in those without OA with 25–34%/8–16% reductions in in-person HCC/hospitalization. On contrary, there were increases in remote HCC following the pandemic (5–25% and 11–31% in people with and without OA, respectively). Among persons with OA, there were variations in the pandemic's effects by sex, age and comorbidity. Conclusion Despite no lockdown in Sweden there were substantial reductions in in-person healthcare use during the first wave of COVID-19 pandemic with greater reductions among people with than without OA.

@article{dellisola_does_2022,
	title = {Does osteoarthritis modify the association between {NSAID} use and risk of comorbidities and adverse events?},
	volume = {4},
	issn = {2665-9131},
	url = {https://www.sciencedirect.com/science/article/pii/S2665913122000218},
	doi = {10.1016/j.ocarto.2022.100253},
	abstract = {Objectives
To investigate the role of osteoarthritis (OA) in the incidence of musculoskeletal, metabolic, cardiovascular, digestive, neuro-psychological, kidney and other comorbidities/adverse events after (i) incident non-steroidal anti-inflammatory drug (NSAID) initiation and (ii) NSAID discontinuation.
Methods
We used register data for the population of Skåne, Sweden. For (i), we analysed the association between starting NSAIDs and the risk of incident outcome events in the 6 years following NSAID dispensation among people with prevalent OA vs no OA. For (ii) we studied the effect of discontinuing NSAIDs among people with and without OA up to 120 days. We used flexible parametric models to estimate adjusted differences in cumulative incidence with NSAIDs as time-varying exposure in the presence of non-proportional hazards.
Results
For (i) we included between 243,832 and 409,749 persons. In the whole cohort, over the 6 years of follow-up, NSAID initiation was associated with a 3\% (metabolic) to 16\% (musculoskeletal) higher cumulative incidence of outcomes compared to non-users. The difference between those initiating NSAIDs vs non-users was similar in those with and without OA for most outcomes, but in those with OA the increase was lower for neuro-psychological (95\%CI: 3.7\%–4.6\% vs 7.1\%–7.9\%) and musculoskeletal comorbidities (12\%–14.5\% vs 16.2\%–17.2\%). In (ii), we found no interaction between OA and NSAID discontinuation. NSAID discontinuation was associated with decreased risks for most of the outcomes, from −1.3\% for musculoskeletal to −0.4\% for cardiovascular comorbidities.
Conclusions
OA appears to have little influence on the increased risk of comorbidities observed after NSAID initiation or decrease after discontinuation.},
	language = {en},
	number = {2},
	urldate = {2023-02-02},
	journal = {Osteoarthritis and Cartilage Open},
	author = {Dell’Isola, Andrea and Turkiewicz, Aleksandra and Zhang, Weiya and Kiadaliri, Ali and Bierma-Zeinstra, Sita and Runhaar, Jos and Prieto-Alhambra, Daniel and Englund, Martin},
	month = jun,
	year = {2022},
	note = {Number: 2},
	keywords = {Comorbidity, Hip, Knee, NSAID, Osteoarthritis},
	pages = {100253},
}

Objectives To investigate the role of osteoarthritis (OA) in the incidence of musculoskeletal, metabolic, cardiovascular, digestive, neuro-psychological, kidney and other comorbidities/adverse events after (i) incident non-steroidal anti-inflammatory drug (NSAID) initiation and (ii) NSAID discontinuation. Methods We used register data for the population of Skåne, Sweden. For (i), we analysed the association between starting NSAIDs and the risk of incident outcome events in the 6 years following NSAID dispensation among people with prevalent OA vs no OA. For (ii) we studied the effect of discontinuing NSAIDs among people with and without OA up to 120 days. We used flexible parametric models to estimate adjusted differences in cumulative incidence with NSAIDs as time-varying exposure in the presence of non-proportional hazards. Results For (i) we included between 243,832 and 409,749 persons. In the whole cohort, over the 6 years of follow-up, NSAID initiation was associated with a 3% (metabolic) to 16% (musculoskeletal) higher cumulative incidence of outcomes compared to non-users. The difference between those initiating NSAIDs vs non-users was similar in those with and without OA for most outcomes, but in those with OA the increase was lower for neuro-psychological (95%CI: 3.7%–4.6% vs 7.1%–7.9%) and musculoskeletal comorbidities (12%–14.5% vs 16.2%–17.2%). In (ii), we found no interaction between OA and NSAID discontinuation. NSAID discontinuation was associated with decreased risks for most of the outcomes, from −1.3% for musculoskeletal to −0.4% for cardiovascular comorbidities. Conclusions OA appears to have little influence on the increased risk of comorbidities observed after NSAID initiation or decrease after discontinuation.

@article{dellisola_association_2022,
	title = {The association between preexisting conditions and osteoarthritis development in peripheral joints: {A} population based nested case-control study},
	volume = {4},
	issn = {2665-9131},
	shorttitle = {The association between preexisting conditions and osteoarthritis development in peripheral joints},
	url = {https://www.sciencedirect.com/science/article/pii/S2665913122000334},
	doi = {10.1016/j.ocarto.2022.100265},
	abstract = {Aim
To study the risk of receiving a new (incident) osteoarthritis (OA) diagnosis in different joint sites based on conditions diagnosed in the 20 years prior the OA diagnosis.
Methods
We used register data for the entire population of the Skåne region (Sweden) to perform a nested case-control study. The outcome was newly diagnosed (incident) OA in peripheral joints, i.e. knee (ICD-10 code M17), hip (M16) and other joints (M15, M18, M19), diagnosed in 2018 or 2019 in persons aged 45+ years with 20 years of register coverage. For each OA case, we sampled 1 control matched on age (1-year strata), sex and residential area in the year of index date using incidence density sampling. The exposures of interest comprised 50 comorbidities. We used adjusted conditional logistic regression for analysis.
Results
Between January 1st, 2018 and December 31st, 2019, we identified 7 201, 2 895, and 7863 persons, respectively, with newly diagnosed knee, hip and other OA. Hypertension, back pain, gout, allergy, depression, anxiety and migraine were all associated with increased risk of knee OA diagnosis, while only gastroesophageal reflux disease and back pain were associated with newly diagnosed hip OA. Interestingly, many of the analysed conditions were associated with increased risk of OA diagnosis in other peripheral joints, including diagnosed generalised OA.
Conclusions
The risk of being diagnosed with OA increases with the presence of multimorbidity earlier in life, but the associations seem to differ between weight-bearing and non-weight-bearing joints.},
	language = {en},
	number = {2},
	urldate = {2023-02-02},
	journal = {Osteoarthritis and Cartilage Open},
	author = {Dell’Isola, Andrea and Turkiewicz, Aleksandra and Zhang, Weiya and Bierma-Zeinstra, Sita and Runhaar, Jos and Prieto-Alhambra, Daniel and Swain, Subhashisa and Kiadaliri, Ali and Englund, Martin},
	month = jun,
	year = {2022},
	note = {Number: 2},
	keywords = {Hip, Incidence, Knee, Multimorbidity, Osteoarthritis},
	pages = {100265},
}

Aim To study the risk of receiving a new (incident) osteoarthritis (OA) diagnosis in different joint sites based on conditions diagnosed in the 20 years prior the OA diagnosis. Methods We used register data for the entire population of the Skåne region (Sweden) to perform a nested case-control study. The outcome was newly diagnosed (incident) OA in peripheral joints, i.e. knee (ICD-10 code M17), hip (M16) and other joints (M15, M18, M19), diagnosed in 2018 or 2019 in persons aged 45+ years with 20 years of register coverage. For each OA case, we sampled 1 control matched on age (1-year strata), sex and residential area in the year of index date using incidence density sampling. The exposures of interest comprised 50 comorbidities. We used adjusted conditional logistic regression for analysis. Results Between January 1st, 2018 and December 31st, 2019, we identified 7 201, 2 895, and 7863 persons, respectively, with newly diagnosed knee, hip and other OA. Hypertension, back pain, gout, allergy, depression, anxiety and migraine were all associated with increased risk of knee OA diagnosis, while only gastroesophageal reflux disease and back pain were associated with newly diagnosed hip OA. Interestingly, many of the analysed conditions were associated with increased risk of OA diagnosis in other peripheral joints, including diagnosed generalised OA. Conclusions The risk of being diagnosed with OA increases with the presence of multimorbidity earlier in life, but the associations seem to differ between weight-bearing and non-weight-bearing joints.

@article{xie_trends_2022,
	title = {Trends of dispensed opioids in {Catalonia}, {Spain}, 2007–19: a population-based cohort study of over 5 million individuals},
	volume = {13},
	issn = {1663-9812},
	shorttitle = {Trends of dispensed opioids in catalonia, spain, 2007–19},
	url = {https://www.frontiersin.org/articles/10.3389/fphar.2022.912361},
	abstract = {Objective: To characterize the trend of opioid use (number of users, dispensations and oral morphine milligram equivalents) in Catalonia (Spain).Design, setting, and participants: This population-based cohort study included all individuals aged 18 years or older, registered in the Information System for Research in Primary Care (SIDIAP), which covers {\textgreater}75\% of the population in Catalonia, Spain, from 1 January 2007, to 31 December 2019.Main exposure and outcomes: The exposures were all commercialized opioids and their combinations (ATC-codes): codeine, tramadol, oxycodone, tapentadol, fentanyl, morphine, and other opioids (dihydrocodeine, hydromorphone, dextropropoxyphene, buprenorphine, pethidine, pentazocine). The main outcomes were the annual figures per 1,000 individuals of 1) opioid users, 2) dispensations, and 3) oral morphine milligram equivalents (MME). Results were stratified separately by opioid types, age (5-year age groups), sex (male or female), living area (rural or urban), and socioeconomic status (from least, U1, to most deprived, U5). The overall trends were quantified using the percentage change (PC) between 2007 and 2019.Results: Among 4,656,197 and 4,798,114 residents from 2007 to 2019, the number of opioid users, dispensations and morphine milligram equivalents per 1,000 individuals increased 12\% (percentage change: 95\% confidence interval (CI) 11.9–12.3\%), 105\% (95\% confidence interval 83\%–126\%) and 339\% (95\% CI 289\%–390\%) respectively. Tramadol represented the majority of opioid use in 2019 (61, 59, and 54\% of opioid users, dispensations, and total MME, respectively). Individuals aged 80 years or over reported the sharpest increase regarding opioid users (PC: 162\%), dispensations (PC: 424\%), and MME (PC: 830\%). Strong opioids were increasingly prescribed for non-cancer pains over the years.Conclusion: Despite the modest increase of opioid users, opioid dispensations and MME increased substantially, particularly in the older population. In addition, strong opioids were incrementally indicated for non-cancer pains over the years. These findings suggest a transition of opioid prescriptions from intermittent to chronic and weak to strong and call for more rigorous opioid stewardship.},
	urldate = {2022-08-26},
	journal = {Frontiers in Pharmacology},
	author = {Xie, Junqing and Strauss, Victoria Y. and Collins, Gary S. and Khalid, Sara and Delmestri, Antonella and Turkiewicz, Aleksandra and Englund, Martin and Tadrous, Mina and Reyes, Carlen and Prieto-Alhambra, Daniel},
	month = jun,
	year = {2022},
}

Objective: To characterize the trend of opioid use (number of users, dispensations and oral morphine milligram equivalents) in Catalonia (Spain).Design, setting, and participants: This population-based cohort study included all individuals aged 18 years or older, registered in the Information System for Research in Primary Care (SIDIAP), which covers \textgreater75% of the population in Catalonia, Spain, from 1 January 2007, to 31 December 2019.Main exposure and outcomes: The exposures were all commercialized opioids and their combinations (ATC-codes): codeine, tramadol, oxycodone, tapentadol, fentanyl, morphine, and other opioids (dihydrocodeine, hydromorphone, dextropropoxyphene, buprenorphine, pethidine, pentazocine). The main outcomes were the annual figures per 1,000 individuals of 1) opioid users, 2) dispensations, and 3) oral morphine milligram equivalents (MME). Results were stratified separately by opioid types, age (5-year age groups), sex (male or female), living area (rural or urban), and socioeconomic status (from least, U1, to most deprived, U5). The overall trends were quantified using the percentage change (PC) between 2007 and 2019.Results: Among 4,656,197 and 4,798,114 residents from 2007 to 2019, the number of opioid users, dispensations and morphine milligram equivalents per 1,000 individuals increased 12% (percentage change: 95% confidence interval (CI) 11.9–12.3%), 105% (95% confidence interval 83%–126%) and 339% (95% CI 289%–390%) respectively. Tramadol represented the majority of opioid use in 2019 (61, 59, and 54% of opioid users, dispensations, and total MME, respectively). Individuals aged 80 years or over reported the sharpest increase regarding opioid users (PC: 162%), dispensations (PC: 424%), and MME (PC: 830%). Strong opioids were increasingly prescribed for non-cancer pains over the years.Conclusion: Despite the modest increase of opioid users, opioid dispensations and MME increased substantially, particularly in the older population. In addition, strong opioids were incrementally indicated for non-cancer pains over the years. These findings suggest a transition of opioid prescriptions from intermittent to chronic and weak to strong and call for more rigorous opioid stewardship.

@article{finnila_mineral_2022,
	title = {Mineral crystal thickness in calcified cartilage and subchondral bone in healthy and osteoarthritic human knees},
	volume = {37},
	issn = {1523-4681},
	url = {https://onlinelibrary.wiley.com/doi/abs/10.1002/jbmr.4642},
	doi = {10.1002/jbmr.4642},
	abstract = {Osteoarthritis (OA) is the most common joint disease, where articular cartilage degradation is often accompanied with sclerosis of the subchondral bone. However, the association between OA and tissue mineralization at the nanostructural level is currently not understood. In particular, it is technically challenging to study calcified cartilage, where relevant but poorly understood pathological processes such as tidemark multiplication and advancement occur. Here, we used state-of-the-art microfocus small-angle X-ray scattering with a 5-μm spatial resolution to determine the size and organization of the mineral crystals at the nanostructural level in human subchondral bone and calcified cartilage. Specimens with a wide spectrum of OA severities were acquired from both medial and lateral compartments of medial compartment knee OA patients (n = 15) and cadaver knees (n = 10). Opposing the common notion, we found that calcified cartilage has thicker and more mutually aligned mineral crystals than adjoining bone. In addition, we, for the first time, identified a well-defined layer of calcified cartilage associated with pathological tidemark multiplication, containing 0.32 nm thicker crystals compared to the rest of calcified cartilage. Finally, we found 0.2 nm thicker mineral crystals in both tissues of the lateral compartment in OA compared with healthy knees, indicating a loading-related disease process because the lateral compartment is typically less loaded in medial compartment knee OA. In summary, we report novel changes in mineral crystal thickness during OA. Our data suggest that unloading in the knee might be involved with the growth of mineral crystals, which is especially evident in the calcified cartilage. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).},
	language = {en},
	number = {9},
	urldate = {2022-09-19},
	journal = {Journal of Bone and Mineral Research},
	author = {Finnilä, Mikko A.J. and Das Gupta, Shuvashis and Turunen, Mikael J. and Hellberg, Iida and Turkiewicz, Aleksandra and Lutz-Bueno, Viviane and Jonsson, Elin and Holler, Mirko and Ali, Neserin and Hughes, Velocity and Isaksson, Hanna and Tjörnstrand, Jon and Önnerfjord, Patrik and Guizar-Sicairos, Manuel and Saarakkala, Simo and Englund, Martin},
	month = sep,
	year = {2022},
	note = {Number: 9
\_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/jbmr.4642},
	keywords = {ANALYSIS/QUANTITATION OF BONE, BONE MODELING AND REMODELING, COLLAGEN, MATRIX MINERALIZATION, OSTEOARTHRITIS},
	pages = {1700--1710},
}

Osteoarthritis (OA) is the most common joint disease, where articular cartilage degradation is often accompanied with sclerosis of the subchondral bone. However, the association between OA and tissue mineralization at the nanostructural level is currently not understood. In particular, it is technically challenging to study calcified cartilage, where relevant but poorly understood pathological processes such as tidemark multiplication and advancement occur. Here, we used state-of-the-art microfocus small-angle X-ray scattering with a 5-μm spatial resolution to determine the size and organization of the mineral crystals at the nanostructural level in human subchondral bone and calcified cartilage. Specimens with a wide spectrum of OA severities were acquired from both medial and lateral compartments of medial compartment knee OA patients (n = 15) and cadaver knees (n = 10). Opposing the common notion, we found that calcified cartilage has thicker and more mutually aligned mineral crystals than adjoining bone. In addition, we, for the first time, identified a well-defined layer of calcified cartilage associated with pathological tidemark multiplication, containing 0.32 nm thicker crystals compared to the rest of calcified cartilage. Finally, we found 0.2 nm thicker mineral crystals in both tissues of the lateral compartment in OA compared with healthy knees, indicating a loading-related disease process because the lateral compartment is typically less loaded in medial compartment knee OA. In summary, we report novel changes in mineral crystal thickness during OA. Our data suggest that unloading in the knee might be involved with the growth of mineral crystals, which is especially evident in the calcified cartilage. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

@article{tayfur_variation_2022,
	title = {Variation in patient-reported outcomes in young and old patients up to 4 to 6 years after arthroscopic partial meniscectomy},
	volume = {32},
	issn = {1050-642X},
	url = {https://journals.lww.com/cjsportsmed/Abstract/2022/09000/Variation_in_Patient_Reported_Outcomes_in_Young.13.aspx},
	doi = {10.1097/JSM.0000000000001011},
	abstract = {Objective: 
        To assess the variation in changes in patient-reported outcomes 4 to 6 years after arthroscopic partial meniscectomy (APM).
        Design: 
        Prospective cohort study.
        Setting: 
        Orthopedic departments at public hospitals.
        Patients: 
        Patients (n = 447) from the Knee Arthroscopy Cohort Southern Denmark undergoing APM.
        Interventions: 
        All patients underwent APM.
        Main Outcome Measures: 
        Change in KOOS4 scores from baseline before surgery to ∼5 years (range 4-6 years) after surgery. KOOS4 is the average aggregated score of 4 of 5 of the Knee injury and Osteoarthritis Outcome Score (KOOS) excluding the activities of daily living subscale (minimal clinical important improvement ∼10 points). A mixed linear model adjusted for sex and body mass index was used to assess change from baseline to ∼5-year follow-up. Change in KOOS4 was divided into 5 categories based on change from baseline to ∼5-year follow-up: {\textless}0 points, 0 to 9 points, 10 to 19 points, 20 to 29 points, and ≥30 points.
        Results: 
        On average, patient-reported outcomes continued to improve from baseline to ∼5-year follow-up (mean KOOS4 change: 26, 95\% CI, 24-28). Proportions in the different response groups were {\textless}0 points (12\%), 0 to 9 points (13\%), 10 to 19 points (16\%), 20 to 29 points (19\%), and ≥30 points (40\%), with no difference between younger (≤40 years, n = 75) and older ({\textgreater}40 years, n = 337) patients (P = 0.898).
        Conclusions: 
        Patient-reported outcomes on average improved up to ∼5 years after APM; however, large variability was observed. The similar variability in younger and older patients questions the assumption that younger patients with traumatic injuries experience larger benefits from APM.},
	language = {en-US},
	number = {5},
	urldate = {2022-10-10},
	journal = {Clinical Journal of Sport Medicine},
	author = {Tayfur, Beyza and Pihl, Kenneth and Varnum, Claus and Lohmander, Stefan and Englund, Martin and Thorlund, Jonas Bloch},
	month = sep,
	year = {2022},
	note = {Number: 5},
	pages = {523--530},
}

Objective:  To assess the variation in changes in patient-reported outcomes 4 to 6 years after arthroscopic partial meniscectomy (APM). Design:  Prospective cohort study. Setting:  Orthopedic departments at public hospitals. Patients:  Patients (n = 447) from the Knee Arthroscopy Cohort Southern Denmark undergoing APM. Interventions:  All patients underwent APM. Main Outcome Measures:  Change in KOOS4 scores from baseline before surgery to ∼5 years (range 4-6 years) after surgery. KOOS4 is the average aggregated score of 4 of 5 of the Knee injury and Osteoarthritis Outcome Score (KOOS) excluding the activities of daily living subscale (minimal clinical important improvement ∼10 points). A mixed linear model adjusted for sex and body mass index was used to assess change from baseline to ∼5-year follow-up. Change in KOOS4 was divided into 5 categories based on change from baseline to ∼5-year follow-up: \textless0 points, 0 to 9 points, 10 to 19 points, 20 to 29 points, and ≥30 points. Results:  On average, patient-reported outcomes continued to improve from baseline to ∼5-year follow-up (mean KOOS4 change: 26, 95% CI, 24-28). Proportions in the different response groups were \textless0 points (12%), 0 to 9 points (13%), 10 to 19 points (16%), 20 to 29 points (19%), and ≥30 points (40%), with no difference between younger (≤40 years, n = 75) and older (\textgreater40 years, n = 337) patients (P = 0.898). Conclusions:  Patient-reported outcomes on average improved up to ∼5 years after APM; however, large variability was observed. The similar variability in younger and older patients questions the assumption that younger patients with traumatic injuries experience larger benefits from APM.

@article{lindeus_socioeconomic_2022,
	title = {Socioeconomic inequalities in all-cause and cause-specific mortality among patients with osteoarthritis in the {Skåne} region, {Sweden}},
	volume = {74},
	copyright = {This article is protected by copyright. All rights reserved.},
	issn = {2151-4658},
	url = {https://onlinelibrary.wiley.com/doi/abs/10.1002/acr.24613},
	doi = {https://doi.org/10.1002/acr.24613},
	abstract = {Objective To assess the association between education and all-cause and cause-specific mortality among patients with osteoarthritis (OA) in comparison to an OA-free reference cohort. Methods Using data from the Skåne healthcare register, we identified all residents aged ≥45 years in the region of Skåne, with doctor-diagnosed OA of peripheral joints between 1998 and 2013 (n=123,993). We created an age and sex-matched reference cohort without OA diagnosis (n=121,318). Subjects were followed until death, relocation outside Skåne, or the end of 2014. The relative index of inequality (RII) and the slope index of inequality (SII) were estimated by the Cox model and Aalen´s additive hazard model, respectively. Results We found an inverse association between education and mortality. The magnitude of relative inequalities in all-cause mortality were comparable in the OA (RII 1.53, 95\% CI:1.46, 1.61) and reference cohorts (RII:1.54, 95\% CI:1.47, 1.62). The absolute inequalities were smaller in the OA (SII 937 all-cause deaths per 100,000 person-years, 95\% CI:811, 1063) compared with the reference cohort (SII 1265, 95\% CI:1109, 1421). Cardiovascular mortality contributed more to the absolute inequalities in the OA than in the reference cohort (60.1\% vs. 48.1\%) while the opposite was observed for cancer mortality (8.5\% vs. 22.3\%). Conclusion We found higher all-cause and cause-specific mortality in OA patients with lower education. The observed inequalities in the OA cohort reflect the inequalities in the population at large. The greater burden of cardiovascular diseases in OA patients suggests that proper management of cardiovascular risk factors in OA patients is important.},
	language = {en},
	number = {10},
	urldate = {2021-04-08},
	journal = {Arthritis Care \& Research},
	author = {Lindéus, Maria and Turkiewicz, Aleksandra and Englund, Martin and Kiadaliri, Ali},
	month = oct,
	year = {2022},
	note = {Number: 10
\_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/acr.24613},
	keywords = {Education, Inequalities, Mortality, Osteoarthritis},
	pages = {1704--1712},
}

Objective To assess the association between education and all-cause and cause-specific mortality among patients with osteoarthritis (OA) in comparison to an OA-free reference cohort. Methods Using data from the Skåne healthcare register, we identified all residents aged ≥45 years in the region of Skåne, with doctor-diagnosed OA of peripheral joints between 1998 and 2013 (n=123,993). We created an age and sex-matched reference cohort without OA diagnosis (n=121,318). Subjects were followed until death, relocation outside Skåne, or the end of 2014. The relative index of inequality (RII) and the slope index of inequality (SII) were estimated by the Cox model and Aalen´s additive hazard model, respectively. Results We found an inverse association between education and mortality. The magnitude of relative inequalities in all-cause mortality were comparable in the OA (RII 1.53, 95% CI:1.46, 1.61) and reference cohorts (RII:1.54, 95% CI:1.47, 1.62). The absolute inequalities were smaller in the OA (SII 937 all-cause deaths per 100,000 person-years, 95% CI:811, 1063) compared with the reference cohort (SII 1265, 95% CI:1109, 1421). Cardiovascular mortality contributed more to the absolute inequalities in the OA than in the reference cohort (60.1% vs. 48.1%) while the opposite was observed for cancer mortality (8.5% vs. 22.3%). Conclusion We found higher all-cause and cause-specific mortality in OA patients with lower education. The observed inequalities in the OA cohort reflect the inequalities in the population at large. The greater burden of cardiovascular diseases in OA patients suggests that proper management of cardiovascular risk factors in OA patients is important.

@article{einarsson_phase-contrast_2022,
	title = {Phase-contrast enhanced synchrotron micro-tomography of human meniscus tissue},
	volume = {30},
	issn = {1063-4584},
	url = {https://www.sciencedirect.com/science/article/pii/S1063458422007671},
	doi = {10.1016/j.joca.2022.06.003},
	abstract = {Objective
To investigate the feasibility of synchrotron radiation-based phase contrast enhanced micro-computed tomography (SR-PhC-μCT) for imaging of human meniscus. Quantitative parameters related to fiber orientation and crimping were evaluated as potential markers of tissue degeneration.
Design
Human meniscus specimens from 10 deceased donors were prepared using different preparation schemes: fresh frozen and thawed before imaging or fixed and paraffin-embedded. The samples were imaged using SR-PhC-μCT with an isotropic voxel size of 1.625 μm. Image quality was evaluated by visual inspection and spatial resolution. Fiber voxels were defined using a grey level threshold and a structure tensor analysis was applied to estimate collagen fiber orientation. The area at half maximum (FAHM) was calculated from angle histograms to quantify orientation distribution. Crimping period was calculated from the power spectrum of image profiles of crimped fibers. Parameters were compared to degenerative stage as evaluated by Pauli histopathological scoring.
Results
Image quality was similar between frozen and embedded samples and spatial resolutions ranged from 5.1 to 5.8 μm. Fiber structure, including crimping, was clearly visible in the images. Fibers appeared to be less organized closer to the tip of the meniscus. Fiber density might decrease slightly with degeneration. FAHM and crimping period did not show any clear association with histopathological scoring.
Conclusion
SR-PhC-μCT is a feasible technique for high-resolution 3D imaging of fresh frozen meniscus tissue. Further work is needed to establish quantitative parameters that relate to tissue degeneration, but this imaging technique is promising for future studies of meniscus structure and biomechanical response.},
	language = {en},
	number = {9},
	urldate = {2022-08-26},
	journal = {Osteoarthritis and Cartilage},
	author = {Einarsson, E. and Pierantoni, M. and Novak, V. and Svensson, J. and Isaksson, H. and Englund, M.},
	month = sep,
	year = {2022},
	note = {Number: 9},
	keywords = {Collagen fiber, Crimp, Synchrotron radiation},
	pages = {1222--1233},
}

Objective To investigate the feasibility of synchrotron radiation-based phase contrast enhanced micro-computed tomography (SR-PhC-μCT) for imaging of human meniscus. Quantitative parameters related to fiber orientation and crimping were evaluated as potential markers of tissue degeneration. Design Human meniscus specimens from 10 deceased donors were prepared using different preparation schemes: fresh frozen and thawed before imaging or fixed and paraffin-embedded. The samples were imaged using SR-PhC-μCT with an isotropic voxel size of 1.625 μm. Image quality was evaluated by visual inspection and spatial resolution. Fiber voxels were defined using a grey level threshold and a structure tensor analysis was applied to estimate collagen fiber orientation. The area at half maximum (FAHM) was calculated from angle histograms to quantify orientation distribution. Crimping period was calculated from the power spectrum of image profiles of crimped fibers. Parameters were compared to degenerative stage as evaluated by Pauli histopathological scoring. Results Image quality was similar between frozen and embedded samples and spatial resolutions ranged from 5.1 to 5.8 μm. Fiber structure, including crimping, was clearly visible in the images. Fibers appeared to be less organized closer to the tip of the meniscus. Fiber density might decrease slightly with degeneration. FAHM and crimping period did not show any clear association with histopathological scoring. Conclusion SR-PhC-μCT is a feasible technique for high-resolution 3D imaging of fresh frozen meniscus tissue. Further work is needed to establish quantitative parameters that relate to tissue degeneration, but this imaging technique is promising for future studies of meniscus structure and biomechanical response.

@article{dellisola_risk_2022,
	title = {Risk of comorbidities following physician-diagnosed knee or hip osteoarthritis: a register-based cohort study},
	volume = {74},
	issn = {2151-4658},
	shorttitle = {Risk of comorbidities following physician-diagnosed knee or hip osteoarthritis},
	url = {https://onlinelibrary.wiley.com/doi/abs/10.1002/acr.24717},
	doi = {10.1002/acr.24717},
	abstract = {Objective To estimate the risk of developing comorbidities in patients after physician-diagnosed knee or hip osteoarthritis (OA). Design Cohort study using Swedish longitudinal healthcare register data; we studied residents in the Skåne region aged ≥35 years at January 1, 2010 free from diagnosed hip or knee OA (n= 548,681). We then identified subjects with at least one new diagnosis of knee or hip OA (incident OA) between 2010 and 2017 (n=50,942 considered exposed). Subjects without diagnosed OA were considered unexposed. From January 2010 both unexposed and exposed subjects were observed for the occurrence of 18 different pre-defined comorbidities until either relocation outside of the region, death, occurrence of the comorbidity, or December 2017, whichever came first. We calculated unadjusted and adjusted hazard ratios (HR, aHR) of comorbidities using Cox models with knee and hip OA as time-varying exposures. Results Subjects with incident knee or hip OA had 7\% to 60\% higher adjusted hazards (aHR between 1.07 to 1.60), of depression, cardiovascular diseases, back pain, and osteoporosis than individuals without an OA diagnosis. An increased risk of diabetes was found only for knee OA (aHR 1.19, 95\% CI 1.13-1.26). For the rest of the diagnoses, we found either no increased risk or estimates with wide confidence intervals, excluding clear interpretations of the direction or size of effects. Conclusions Incident physician-diagnosed knee and hip OA is associated with increased risk of depression, cardiovascular diseases, back pain, osteoporosis, and diabetes. However, the latter only for knee OA.},
	language = {en},
	number = {10},
	urldate = {2021-09-06},
	journal = {Arthritis Care \& Research},
	author = {Dell’Isola, Andrea and Pihl, Kenneth and Turkiewicz, Aleksandra and Hughes, Velocity and Zhang, Weiya and Bierma-Zeinstra, Sita and Prieto-Alhambra, Daniel and Englund, Martin},
	month = oct,
	year = {2022},
	note = {Number: 10
\_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/acr.24717},
	keywords = {Comorbidity, Epidemiology, Osteoarthritis, hip, knee},
	pages = {1689--1695},
}

Objective To estimate the risk of developing comorbidities in patients after physician-diagnosed knee or hip osteoarthritis (OA). Design Cohort study using Swedish longitudinal healthcare register data; we studied residents in the Skåne region aged ≥35 years at January 1, 2010 free from diagnosed hip or knee OA (n= 548,681). We then identified subjects with at least one new diagnosis of knee or hip OA (incident OA) between 2010 and 2017 (n=50,942 considered exposed). Subjects without diagnosed OA were considered unexposed. From January 2010 both unexposed and exposed subjects were observed for the occurrence of 18 different pre-defined comorbidities until either relocation outside of the region, death, occurrence of the comorbidity, or December 2017, whichever came first. We calculated unadjusted and adjusted hazard ratios (HR, aHR) of comorbidities using Cox models with knee and hip OA as time-varying exposures. Results Subjects with incident knee or hip OA had 7% to 60% higher adjusted hazards (aHR between 1.07 to 1.60), of depression, cardiovascular diseases, back pain, and osteoporosis than individuals without an OA diagnosis. An increased risk of diabetes was found only for knee OA (aHR 1.19, 95% CI 1.13-1.26). For the rest of the diagnoses, we found either no increased risk or estimates with wide confidence intervals, excluding clear interpretations of the direction or size of effects. Conclusions Incident physician-diagnosed knee and hip OA is associated with increased risk of depression, cardiovascular diseases, back pain, osteoporosis, and diabetes. However, the latter only for knee OA.