Publications

@article{turkiewicz_antihistamine_2025,
	title = {Antihistamine use and osteoarthritis or joint pain},
	volume = {33},
	issn = {1063-4584},
	url = {https://www.sciencedirect.com/science/article/pii/S1063458424013967},
	doi = {10.1016/j.joca.2024.09.004},
	abstract = {Objectives
Antihistamines have been reported to be linked with less pain in osteoarthritis. We aimed to estimate associations between antihistamine use and three outcomes: prevalent osteoarthritis, current joint pain, and developing osteoarthritis.
Methods
We included 25 003 participants of EpiHealth – a cohort of persons aged 45 to 75 from Malmö/Uppsala in Sweden. Participants self-reported the presence of allergy, joint pain and osteoarthritis at a study visit between years 2010 and 2016. Further, we obtained data about diagnoses of allergy and osteoarthritis from health-care registers (primary, specialist and inpatient care). Exposure was prescribed dispensed antihistamines (H1-antagonists) during ∼6 years preceding the EpiHealth visit retrieved from the Prescribed Drugs Register. The outcomes were osteoarthritis (any location), pain in knees/hips/hands-wrists at the examination (cross-sectional) and future incident diagnosis of osteoarthritis (longitudinal, in a cohort free of osteoarthritis at EpiHealth). We report risk ratios (95\% confidence intervals [CI]) from logistic regression and hazard ratios (HR) from Cox regression, from models adjusted for age, sex, body mass index, allergy and use of healthcare. We used prescribed dispensed penicillin as negative control.
Results
The associations between use of antihistamines and osteoarthritis/joint pain at EpiHealth were 1.13 (95\%CI 1.06, 1.20) and 1.02 (0.99, 1.05), respectively. The HR of future incident osteoarthritis diagnosis with use of antihistamines was 1.15 (1.03, 1.28). The association (HR) between penicillin use and future incident osteoarthritis diagnosis was 1.16 (1.07, 1.25).
Conclusions
In a large population-based observational cohort, use of antihistamines was neither associated with less joint pain/osteoarthritis nor lower risk of future osteoarthritis.},
	number = {1},
	urldate = {2025-08-27},
	journal = {Osteoarthritis and Cartilage},
	author = {Turkiewicz, Aleksandra and Hellberg, Clara and Dell’Isola, Andrea and Englund, Martin},
	month = jan,
	year = {2025},
	keywords = {Antihistamine, Epidemiology, Joint pain, Osteoarthritis},
	pages = {176--179},
}

Objectives Antihistamines have been reported to be linked with less pain in osteoarthritis. We aimed to estimate associations between antihistamine use and three outcomes: prevalent osteoarthritis, current joint pain, and developing osteoarthritis. Methods We included 25 003 participants of EpiHealth – a cohort of persons aged 45 to 75 from Malmö/Uppsala in Sweden. Participants self-reported the presence of allergy, joint pain and osteoarthritis at a study visit between years 2010 and 2016. Further, we obtained data about diagnoses of allergy and osteoarthritis from health-care registers (primary, specialist and inpatient care). Exposure was prescribed dispensed antihistamines (H1-antagonists) during ∼6 years preceding the EpiHealth visit retrieved from the Prescribed Drugs Register. The outcomes were osteoarthritis (any location), pain in knees/hips/hands-wrists at the examination (cross-sectional) and future incident diagnosis of osteoarthritis (longitudinal, in a cohort free of osteoarthritis at EpiHealth). We report risk ratios (95% confidence intervals [CI]) from logistic regression and hazard ratios (HR) from Cox regression, from models adjusted for age, sex, body mass index, allergy and use of healthcare. We used prescribed dispensed penicillin as negative control. Results The associations between use of antihistamines and osteoarthritis/joint pain at EpiHealth were 1.13 (95%CI 1.06, 1.20) and 1.02 (0.99, 1.05), respectively. The HR of future incident osteoarthritis diagnosis with use of antihistamines was 1.15 (1.03, 1.28). The association (HR) between penicillin use and future incident osteoarthritis diagnosis was 1.16 (1.07, 1.25). Conclusions In a large population-based observational cohort, use of antihistamines was neither associated with less joint pain/osteoarthritis nor lower risk of future osteoarthritis.

@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},
	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 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 (MOAKS) scoring to derive subregional data on cartilage damage, osteophytes and bone marrow lesions (BMLs). Progression of structural cartilage changes analysed per subregion was the main outcome, that of osteophytes and BMLs secondary outcomes. We analysed 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},
	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},
	pmid = {39277028},
	keywords = {Knee, Knee arthroscopy, Magnetic resonance imaging, Meniscus, Osteoarthritis, Placebo surgery},
	pages = {S1063--4584(24)01398--0},
}

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 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 (MOAKS) scoring to derive subregional data on cartilage damage, osteophytes and bone marrow lesions (BMLs). Progression of structural cartilage changes analysed per subregion was the main outcome, that of osteophytes and BMLs secondary outcomes. We analysed 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{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},
	pmid = {39116991},
	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{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},
	pmid = {37639149},
	pmcid = {PMC10774176},
	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{johansson_use_2024,
	title = {Use of prescribed analgesics before and after exercise therapy and patient education in patients with knee or hip osteoarthritis},
	volume = {44},
	issn = {1437-160X},
	url = {https://doi.org/10.1007/s00296-023-05432-0},
	doi = {10.1007/s00296-023-05432-0},
	abstract = {The aim of this study was to investigate utilisation patterns of prescribed analgesics before, during, and after an exercise therapy and patient education program among patients with knee or hip osteoarthritis. This cohort study is based on data from the nationwide Good Life with osteoarthritis in Denmark (GLA:D®) patient-register linked with national health registries including data on prescribed analgesics. GLA:D® consists of 8–12 weeks of exercise and patient education. We included 35,549 knee/hip osteoarthritis patients starting the intervention between January 2013 and November 2018. Utilisation patterns the year before, 3 months during, and the year after the intervention were investigated using total dispensed defined daily doses (DDDs) per month per 1000 population as outcome. During the year before the intervention, use of prescribed paracetamol, non-steroidal anti-inflammatory drugs (NSAIDs), and opioids increased with 85\%, 79\% and 22\%, respectively. During the intervention, use of paracetamol decreased with 16\% with a stable use the following year. Use of NSAIDs and opioids decreased with 38\% and 8\%, respectively, throughout the intervention and the year after. Sensitivity analyses indicated that the prescription of most analgesics changed over time. For paracetamol, NSAIDs, and opioids, 10\% of analgesic users accounted for 45\%, 50\%, and 70\%, respectively, of the total DDDs dispensed during the study period. In general, analgesic use increased the year before the intervention followed by a decrease during the intervention and the year after. A small proportion of analgesic users accounted for half or more of all paracetamol, NSAIDs, and opioids dispensed during the study period.},
	language = {en},
	number = {2},
	urldate = {2023-11-08},
	journal = {Rheumatology International},
	author = {Johansson, Melker S. and Pottegård, Anton and Søndergaard, Jens and Englund, Martin and Grønne, Dorte T. and Skou, Søren T. and Roos, Ewa M. and Thorlund, Jonas B.},
	month = feb,
	year = {2024},
	keywords = {Exercise therapy, Non-steroidal anti-inflammatory drugs, Opioids, Osteoarthritis, Paracetamol, Patient education},
	pages = {319--328},
}

The aim of this study was to investigate utilisation patterns of prescribed analgesics before, during, and after an exercise therapy and patient education program among patients with knee or hip osteoarthritis. This cohort study is based on data from the nationwide Good Life with osteoarthritis in Denmark (GLA:D®) patient-register linked with national health registries including data on prescribed analgesics. GLA:D® consists of 8–12 weeks of exercise and patient education. We included 35,549 knee/hip osteoarthritis patients starting the intervention between January 2013 and November 2018. Utilisation patterns the year before, 3 months during, and the year after the intervention were investigated using total dispensed defined daily doses (DDDs) per month per 1000 population as outcome. During the year before the intervention, use of prescribed paracetamol, non-steroidal anti-inflammatory drugs (NSAIDs), and opioids increased with 85%, 79% and 22%, respectively. During the intervention, use of paracetamol decreased with 16% with a stable use the following year. Use of NSAIDs and opioids decreased with 38% and 8%, respectively, throughout the intervention and the year after. Sensitivity analyses indicated that the prescription of most analgesics changed over time. For paracetamol, NSAIDs, and opioids, 10% of analgesic users accounted for 45%, 50%, and 70%, respectively, of the total DDDs dispensed during the study period. In general, analgesic use increased the year before the intervention followed by a decrease during the intervention and the year after. A small proportion of analgesic users accounted for half or more of all paracetamol, NSAIDs, and opioids dispensed during the study period.

@article{magnusson_genetic_2024,
	title = {Genetic influence to osteoarthritis versus other rheumatic diseases},
	volume = {76},
	copyright = {This article is protected by copyright. All rights reserved.},
	issn = {2326-5205},
	url = {https://onlinelibrary.wiley.com/doi/abs/10.1002/art.42696},
	doi = {10.1002/art.42696},
	abstract = {Aim To compare the genetic contribution to osteoarthritis (OA) vs other rheumatic/musculoskeletal diseases (RMDs) in the same population, and 2) to explore the role for any shared genetics between OA and other RMDs. Methods In 59 970 Swedish twins aged 35 years or older, we estimated the heritability (the variance explained by genetic factors) to OA in peripheral joints, back and neck pain, shoulder pain (adhesive capsulitis, impingement syndrome, etc), rheumatoid arthritis (RA), spondyloarthritis and psoriatic arthritis (SpA/PSA), myalgia and osteoporosis diagnosed in specialist and inpatient care. We also studied how much of covariance between OA and each of the RMDs could be explained by genetics, by studying phenotypic correlations in bivariate classical twin models. Results Any-site OA and hip OA (50\% and 64\%) were among the most heritable RMDs (as compared to 23\% for fibromyalgia (lowest) and 63\% for spondylarthritis (highest)). The highest phenotypic correlations were between OA (any joint site) and shoulder pain in the same individual (r=0.33, 95\% CI=0.31-0.35), of which 70\% (52-88) could be explained by shared genetics. The phenotypic correlation between OA and back/neck pain was r=0.25, with 25\%-75\% explained by genetics. Phenotypic correlations between OA and each of the other RMDs were lower (r 0.1 to r 0.2) with inconclusive sources of variation. Conclusion OA has relatively large heritability as compared to other RMDs. The co-existence of OA and shoulder pain, as well as back pain, was common and could often be explained by genetic factors. Findings imply similar etiologies of OA and several pain conditions.},
	language = {en},
	number = {2},
	urldate = {2023-10-02},
	journal = {Arthritis \& Rheumatology},
	author = {Magnusson, Karin and Turkiewicz, Aleksandra and Rydén, Martin and Englund, Martin},
	month = feb,
	year = {2024},
	note = {\_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/art.42696},
	pages = {206--215},
}

Aim To compare the genetic contribution to osteoarthritis (OA) vs other rheumatic/musculoskeletal diseases (RMDs) in the same population, and 2) to explore the role for any shared genetics between OA and other RMDs. Methods In 59 970 Swedish twins aged 35 years or older, we estimated the heritability (the variance explained by genetic factors) to OA in peripheral joints, back and neck pain, shoulder pain (adhesive capsulitis, impingement syndrome, etc), rheumatoid arthritis (RA), spondyloarthritis and psoriatic arthritis (SpA/PSA), myalgia and osteoporosis diagnosed in specialist and inpatient care. We also studied how much of covariance between OA and each of the RMDs could be explained by genetics, by studying phenotypic correlations in bivariate classical twin models. Results Any-site OA and hip OA (50% and 64%) were among the most heritable RMDs (as compared to 23% for fibromyalgia (lowest) and 63% for spondylarthritis (highest)). The highest phenotypic correlations were between OA (any joint site) and shoulder pain in the same individual (r=0.33, 95% CI=0.31-0.35), of which 70% (52-88) could be explained by shared genetics. The phenotypic correlation between OA and back/neck pain was r=0.25, with 25%-75% explained by genetics. Phenotypic correlations between OA and each of the other RMDs were lower (r 0.1 to r 0.2) with inconclusive sources of variation. Conclusion OA has relatively large heritability as compared to other RMDs. The co-existence of OA and shoulder pain, as well as back pain, was common and could often be explained by genetic factors. Findings imply similar etiologies of OA and several pain 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},
	pmid = {38229918},
	pmcid = {PMC10790080},
	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{liew_diagnostic_2024,
	title = {Diagnostic accuracy of candidate magnetic resonance imaging knee osteoarthritis definitions versus radiograph in an acute anterior cruciate ligament injury cohort},
	volume = {76},
	copyright = {© 2023 American College of Rheumatology},
	issn = {2151-4658},
	url = {https://onlinelibrary.wiley.com/doi/abs/10.1002/acr.25248},
	doi = {10.1002/acr.25248},
	abstract = {Objective We tested the diagnostic accuracy of previously proposed magnetic resonance imaging (MRI) osteoarthritis (OA) definitions in a cohort after acute anterior cruciate ligament (ACL) injury. Methods We studied participants with posteroanterior and lateral knee radiographs and MRI 5 years after ACL injury, scored using the Anterior Cruciate Ligament Osteoarthritis Score. Radiographic OA (ROA) was defined using Osteoarthritis Research Society International scoring of osteophytes and joint space narrowing considering medial/lateral tibiofemoral and patellofemoral compartments. We tested three candidate MRI OA definitions that performed well in an older adult cohort. “Multicenter Osteoarthritis Study (MOST) simple” required cartilage score ≥2 (range 0–6) and osteophyte score ≥2 (0–7); “MOST optional” included cartilage score ≥2, osteophyte score ≥2, and either bone marrow lesions (BMLs) ≥1 (0–3) or synovitis ≥2 (0–3). The third, a Delphi panel definition, included nonzero scores for cartilage, osteophyte, BMLs, meniscus, and other structures. We calculated sensitivity and specificity with 95\% confidence intervals (95\% CIs) for each MRI definition versus ROA. Results We included 113 participants (mean age 26 years, 26\% female). At 5 years, 29 participants (26\%) had ROA. “MOST simple” had a sensitivity of 52\% (95\% CI 33\%–71\%), and specificity of 76\% (95\% CI 66\%–85\%). Sensitivity and specificities for “MOST optional” were 28\% (95\% CI 29\%–67\%) and 83\% (95\% CI 74\%–91\%), respectively. The Delphi panel definition had a sensitivity of 48\% (95\% CI 29\%–67\%) and specificity of 77\% (95\% CI 67\%–86\%). Conclusion Simple MRI-based OA definitions requiring at least cartilage damage and an osteophyte have low sensitivity and high specificity in young persons after knee injury.},
	language = {en},
	number = {3},
	urldate = {2024-03-06},
	journal = {Arthritis Care \& Research},
	author = {Liew, Jean W. and Turkiewicz, Aleksandra and Roemer, Frank W. and Frobell, Richard B. and Felson, David and Englund, Martin},
	month = mar,
	year = {2024},
	note = {\_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/acr.25248},
	pages = {409--414},
}

Objective We tested the diagnostic accuracy of previously proposed magnetic resonance imaging (MRI) osteoarthritis (OA) definitions in a cohort after acute anterior cruciate ligament (ACL) injury. Methods We studied participants with posteroanterior and lateral knee radiographs and MRI 5 years after ACL injury, scored using the Anterior Cruciate Ligament Osteoarthritis Score. Radiographic OA (ROA) was defined using Osteoarthritis Research Society International scoring of osteophytes and joint space narrowing considering medial/lateral tibiofemoral and patellofemoral compartments. We tested three candidate MRI OA definitions that performed well in an older adult cohort. “Multicenter Osteoarthritis Study (MOST) simple” required cartilage score ≥2 (range 0–6) and osteophyte score ≥2 (0–7); “MOST optional” included cartilage score ≥2, osteophyte score ≥2, and either bone marrow lesions (BMLs) ≥1 (0–3) or synovitis ≥2 (0–3). The third, a Delphi panel definition, included nonzero scores for cartilage, osteophyte, BMLs, meniscus, and other structures. We calculated sensitivity and specificity with 95% confidence intervals (95% CIs) for each MRI definition versus ROA. Results We included 113 participants (mean age 26 years, 26% female). At 5 years, 29 participants (26%) had ROA. “MOST simple” had a sensitivity of 52% (95% CI 33%–71%), and specificity of 76% (95% CI 66%–85%). Sensitivity and specificities for “MOST optional” were 28% (95% CI 29%–67%) and 83% (95% CI 74%–91%), respectively. The Delphi panel definition had a sensitivity of 48% (95% CI 29%–67%) and specificity of 77% (95% CI 67%–86%). Conclusion Simple MRI-based OA definitions requiring at least cartilage damage and an osteophyte have low sensitivity and high specificity in young persons after knee injury.

@article{battista_income-related_2024,
	title = {Income-related inequality changes in osteoarthritis first-line interventions: a cohort study},
	volume = {105},
	issn = {0003-9993},
	shorttitle = {Income-{Related} {Inequality} {Changes} in {Osteoarthritis} {First}-{Line} {Interventions}},
	url = {https://www.sciencedirect.com/science/article/pii/S000399932300607X},
	doi = {10.1016/j.apmr.2023.10.012},
	abstract = {Objective
To examine income-related inequality changes in the outcomes of an osteoarthritis (OA) first-line intervention.
Design
Retrospective cohort study.
Setting
Swedish health care system.
Participants
We included 115,403 people (age: 66.2±9.7 years; females 67.8\%; N=115,403) with knee (67.8\%) or hip OA (32.4\%) recorded in the “Swedish Osteoarthritis Registry” (SOAR).
Interventions
Exercise and education.
Main Outcome Measures
Erreygers’ concentration index (E) measured income-related inequalities in “Pain intensity,” “Self-efficacy,” “Use of NSAIDs,” and “Desire for surgery” at baseline, 3-month, and 12-month follow-ups and their differences over time. E-values range from -1 to +1 if the health variables are more concentrated among people with lower or higher income. Zero represents perfect equality. We used entropy balancing to address demographic and outcome imbalances and bootstrap replications to estimate confidence intervals for E differences over time.
Results
Comparing baseline to 3 months, “pain” concentrated more among individuals with lower income initially (E=-0.027), intensifying at 3 months (difference with baseline: E=-0.011 [95\% CI: -0.014; -0.008]). Similarly, the “Desire for surgery” concentrated more among individuals with lower income initially (E=-0.009), intensifying at 3 months (difference with baseline: E=-0.012 [-0.018; -0.005]). Conversely, “Self-efficacy” concentrated more among individuals with higher income initially (E=0.058), intensifying at 3 months (difference with baseline: E=0.008 [0.004; 0.012]). Lastly, the “Use of NSAIDs” concentrated more among individuals with higher income initially (E=0.068) but narrowed at 3 months (difference with baseline: E=-0.029 [-0.038; -0.021]). Comparing baseline with 12 months, “pain” concentrated more among individuals with lower income initially (E=-0.024), intensifying at 12 months (difference with baseline: E=-0.017 [-0.022; -0.012]). Similarly, the “Desire for surgery” concentrated more among individuals with lower income initially (E=-0.016), intensifying at 12 months (difference with baseline: E=-0.012 [-0.022; -0.002]). Conversely, “Self-efficacy” concentrated more among individuals with higher income initially (E=0.059), intensifying at 12 months (difference with baseline: E=0.016 [0.011; 0.021]). The variable 'Use of NSAIDs' was not recorded in the SOAR at 12-month follow-up.
Conclusion
Our results highlight the increase of income-related inequalities in the SOAR over time.},
	number = {3},
	urldate = {2024-03-06},
	journal = {Archives of Physical Medicine and Rehabilitation},
	author = {Battista, Simone and Kiadaliri, Ali and Jönsson, Thérése and Gustafsson, Kristin and Englund, Martin and Testa, Marco and Dell'Isola, Andrea},
	month = mar,
	year = {2024},
	keywords = {Epidemiology, Health Policy, National Health Programs, Personal Health Services, Physical Therapy Specialty, Rehabilitation},
	pages = {452--460},
}

Objective To examine income-related inequality changes in the outcomes of an osteoarthritis (OA) first-line intervention. Design Retrospective cohort study. Setting Swedish health care system. Participants We included 115,403 people (age: 66.2±9.7 years; females 67.8%; N=115,403) with knee (67.8%) or hip OA (32.4%) recorded in the “Swedish Osteoarthritis Registry” (SOAR). Interventions Exercise and education. Main Outcome Measures Erreygers’ concentration index (E) measured income-related inequalities in “Pain intensity,” “Self-efficacy,” “Use of NSAIDs,” and “Desire for surgery” at baseline, 3-month, and 12-month follow-ups and their differences over time. E-values range from -1 to +1 if the health variables are more concentrated among people with lower or higher income. Zero represents perfect equality. We used entropy balancing to address demographic and outcome imbalances and bootstrap replications to estimate confidence intervals for E differences over time. Results Comparing baseline to 3 months, “pain” concentrated more among individuals with lower income initially (E=-0.027), intensifying at 3 months (difference with baseline: E=-0.011 [95% CI: -0.014; -0.008]). Similarly, the “Desire for surgery” concentrated more among individuals with lower income initially (E=-0.009), intensifying at 3 months (difference with baseline: E=-0.012 [-0.018; -0.005]). Conversely, “Self-efficacy” concentrated more among individuals with higher income initially (E=0.058), intensifying at 3 months (difference with baseline: E=0.008 [0.004; 0.012]). Lastly, the “Use of NSAIDs” concentrated more among individuals with higher income initially (E=0.068) but narrowed at 3 months (difference with baseline: E=-0.029 [-0.038; -0.021]). Comparing baseline with 12 months, “pain” concentrated more among individuals with lower income initially (E=-0.024), intensifying at 12 months (difference with baseline: E=-0.017 [-0.022; -0.012]). Similarly, the “Desire for surgery” concentrated more among individuals with lower income initially (E=-0.016), intensifying at 12 months (difference with baseline: E=-0.012 [-0.022; -0.002]). Conversely, “Self-efficacy” concentrated more among individuals with higher income initially (E=0.059), intensifying at 12 months (difference with baseline: E=0.016 [0.011; 0.021]). The variable 'Use of NSAIDs' was not recorded in the SOAR at 12-month follow-up. Conclusion Our results highlight the increase of income-related inequalities in the SOAR over time.

@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},
	pmid = {38599652},
	pmcid = {PMC11015192},
	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{lindeus_does_2023,
	title = {Does lower educational attainment increase the risk of osteoarthritis surgery? a {Swedish} twin study},
	volume = {24},
	issn = {1471-2474},
	shorttitle = {Does lower educational attainment increase the risk of osteoarthritis surgery?},
	url = {https://doi.org/10.1186/s12891-023-06163-w},
	doi = {10.1186/s12891-023-06163-w},
	abstract = {Previous studies have reported an inverse association between educational attainment and different osteoarthritis (OA) outcomes. However, none of the previous studies have accounted for potential confounding by early-life environment and genetics. Thus, we aimed to examine the association between educational attainment and knee and hip OA surgery using twin data.},
	number = {1},
	urldate = {2023-02-02},
	journal = {BMC Musculoskeletal Disorders},
	author = {Lindéus, Maria and Turkiewicz, Aleksandra and Magnusson, Karin and Englund, Martin and Kiadaliri, Ali},
	month = jan,
	year = {2023},
	note = {Number: 1},
	keywords = {Education, Inequalities, Osteoarthritis surgery, Twin study},
	pages = {72},
}

Previous studies have reported an inverse association between educational attainment and different osteoarthritis (OA) outcomes. However, none of the previous studies have accounted for potential confounding by early-life environment and genetics. Thus, we aimed to examine the association between educational attainment and knee and hip OA surgery using twin data.

@article{isacsson_incidence_2023,
	title = {Incidence and concomitant chondral injuries in a consecutive cohort of primary traumatic patellar dislocations examined with sub-acute {MRI}},
	volume = {47},
	issn = {1432-5195},
	url = {https://doi.org/10.1007/s00264-023-05707-y},
	doi = {10.1007/s00264-023-05707-y},
	abstract = {To present age- and sex-specific cumulative annual incidences of primary traumatic lateral patellar dislocation (LPD) and to detail patient characteristics and concomitant chondral injuries including osteochondral fractures, as visualized on magnetic resonance imaging (MRI), in a large consecutive cohort of knee-injured individuals.},
	language = {en},
	number = {4},
	urldate = {2023-03-06},
	journal = {International Orthopaedics},
	author = {Isacsson, Anders and Olsson, Ola and Englund, Martin and Frobell, Richard B.},
	month = feb,
	year = {2023},
	note = {Number: 4},
	keywords = {Epidemiology, Osteochondral injury, Patellar dislocation, Sports},
	pages = {973--981},
}

To present age- and sex-specific cumulative annual incidences of primary traumatic lateral patellar dislocation (LPD) and to detail patient characteristics and concomitant chondral injuries including osteochondral fractures, as visualized on magnetic resonance imaging (MRI), in a large consecutive cohort of knee-injured individuals.

@article{kiadaliri_incipient_2023,
	title = {Incipient dementia and avoidable hospital admission in persons with osteoarthritis},
	volume = {5},
	issn = {2665-9131},
	url = {https://www.sciencedirect.com/science/article/pii/S2665913123000080},
	doi = {10.1016/j.ocarto.2023.100341},
	abstract = {Objective
To investigate the associations between incipient dementia (ID) and hospitalization for ambulatory care sensitive conditions (ACSCs) among people with osteoarthritis (OA) of the peripheral joints.
Methods
Among individuals aged 51–99 years residing in Skåne, Sweden, in 2009, we identified those with a doctor-diagnosed OA and no dementia during 1998–2009 (n ​= ​57,733). Treating ID as a time-varying exposure, we followed people from January 1, 2010 or their 60th birthday (whichever occurred last) until hospitalization for ACSCs, death, 100th birthday, relocation outside Skåne, or December 31, 2019 (whichever occurred first). Using age as time scale, we applied flexible parametric survival models, adjusted for confounders, to assess the associations between ID and hospitalization for ACSCs.
Results
There were 58 and 33 hospitalizations for ACSCs per 1000 person-years among OA people with and without ID, respectively. The association between ID and hospitalization for any ACSCs was age-dependent with higher risk in ages{\textless}86 years and lower risks in older ages. Between ages 60 and 100 years, persons with ID had, on average, 5.8 (95\% CI 0.9, 10.7), 1.6 (−2.6, 5.9) and 3.1 (2.3, 4.0) fewer hospital-free years for any, chronic and acute ACSCs, respectively, compared with persons without ID.
Conclusions
Among persons with OA, while ID was associated with increased risks of hospitalization for ACSCs in younger ages, it was associated with decreased risk in oldest ages. These results suggest the need for improvement in quality of ambulatory care including the continuity of care for people with OA having dementia.},
	language = {en},
	number = {1},
	urldate = {2023-03-06},
	journal = {Osteoarthritis and Cartilage Open},
	author = {Kiadaliri, Ali and Lohmander, L Stefan and Dahlberg, Leif E. and Englund, Martin},
	month = mar,
	year = {2023},
	note = {Number: 1},
	keywords = {Ambulatory-care sensitive conditions, Avoidable hospitalization, Incipient dementia, Osteoarthritis, Register-based study, Sweden},
	pages = {100341},
}

Objective To investigate the associations between incipient dementia (ID) and hospitalization for ambulatory care sensitive conditions (ACSCs) among people with osteoarthritis (OA) of the peripheral joints. Methods Among individuals aged 51–99 years residing in Skåne, Sweden, in 2009, we identified those with a doctor-diagnosed OA and no dementia during 1998–2009 (n ​= ​57,733). Treating ID as a time-varying exposure, we followed people from January 1, 2010 or their 60th birthday (whichever occurred last) until hospitalization for ACSCs, death, 100th birthday, relocation outside Skåne, or December 31, 2019 (whichever occurred first). Using age as time scale, we applied flexible parametric survival models, adjusted for confounders, to assess the associations between ID and hospitalization for ACSCs. Results There were 58 and 33 hospitalizations for ACSCs per 1000 person-years among OA people with and without ID, respectively. The association between ID and hospitalization for any ACSCs was age-dependent with higher risk in ages\textless86 years and lower risks in older ages. Between ages 60 and 100 years, persons with ID had, on average, 5.8 (95% CI 0.9, 10.7), 1.6 (−2.6, 5.9) and 3.1 (2.3, 4.0) fewer hospital-free years for any, chronic and acute ACSCs, respectively, compared with persons without ID. Conclusions Among persons with OA, while ID was associated with increased risks of hospitalization for ACSCs in younger ages, it was associated with decreased risk in oldest ages. These results suggest the need for improvement in quality of ambulatory care including the continuity of care for people with OA having dementia.

@article{gong_association_2023,
	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},
	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},
	pmid = {36521912},
	note = {Number: 4
Publisher: The Journal of Rheumatology
Section: Article},
	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},
	author = {Magnusson, Karin and Turkiewicz, Aleksandra and Flottorp, Signe Agnes and Englund, Martin},
	month = apr,
	year = {2023},
	note = {Number: 1
Publisher: Nature Publishing Group},
	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},
	author = {Englund, Martin and Turkiewicz, Aleksandra},
	month = apr,
	year = {2023},
	note = {Number: 6
Publisher: Elsevier},
	pages = {E309--E311},
}

@article{dellisola_road_2023,
	title = {Road to total knee replacement: {Utilization} of knee surgeries up to ten years before total knee replacement in {England} and {Sweden}},
	volume = {75},
	copyright = {© 2022 The Authors. Arthritis Care \& Research published by Wiley Periodicals LLC on behalf of American College of Rheumatology.},
	issn = {2151-4658},
	shorttitle = {Road to {Total} {Knee} {Replacement}},
	url = {https://onlinelibrary.wiley.com/doi/abs/10.1002/acr.25033},
	doi = {10.1002/acr.25033},
	abstract = {Objective To compare the prevalence and timing of knee surgery (including meniscal, ligamentous, synovial, and osteotomy) in the 10 years prior to primary total knee replacement (TKR) between England and Sweden. Methods This was a population-based, case–control study within England and southern Sweden using electronic health care databases. Patients underwent primary TKR between 2015 and 2019. Risk-set sampling showed that general population controls matched 1:1 by age, sex, and practice/municipality. The annual prevalence and prevalence ratio of having at least 1 recorded surgery in each of the 10 years preceding TKR was estimated using Poisson regressions. Results We included 6,308 and 47,010 TKR cases in Sweden and England, respectively. Meniscal surgeries were the most frequent procedure prior to TKR in both countries; prevalence was higher in England across all time points. The prevalence of meniscal surgery increased in both countries in the years approaching TKR, reaching 33.2 (95\% confidence interval [95\% CI] 31.6–34.9) per 1,000 persons in England, and 9.83 (95\% CI 7.66–12.61) in Sweden. In England, we observed a decrease from 2014 to 2018 in the utilization of this procedure in the 4 years preceding a TKR. The prevalence of all analyzed surgeries was consistently lower in controls. Conclusion There are comparable trends in the use of knee surgery in the years preceding TKR across England and Sweden. Of note, meniscal surgeries remain common, even within the year prior to TKR, highlighting that these patients may experience low-value care. Careful consideration of knee surgery in those with late-stage disease is required.},
	language = {en},
	number = {5},
	urldate = {2023-06-07},
	journal = {Arthritis Care \& Research},
	author = {Dell'Isola, Andrea and Appleyard, Tom and Yu, Dahai and Hellberg, Clara and Thomas, Geraint and Turkiewicz, Aleksandra and Peat, George and Englund, Martin},
	month = may,
	year = {2023},
	note = {Number: 5
\_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/acr.25033},
	pages = {1104--1112},
}

Objective To compare the prevalence and timing of knee surgery (including meniscal, ligamentous, synovial, and osteotomy) in the 10 years prior to primary total knee replacement (TKR) between England and Sweden. Methods This was a population-based, case–control study within England and southern Sweden using electronic health care databases. Patients underwent primary TKR between 2015 and 2019. Risk-set sampling showed that general population controls matched 1:1 by age, sex, and practice/municipality. The annual prevalence and prevalence ratio of having at least 1 recorded surgery in each of the 10 years preceding TKR was estimated using Poisson regressions. Results We included 6,308 and 47,010 TKR cases in Sweden and England, respectively. Meniscal surgeries were the most frequent procedure prior to TKR in both countries; prevalence was higher in England across all time points. The prevalence of meniscal surgery increased in both countries in the years approaching TKR, reaching 33.2 (95% confidence interval [95% CI] 31.6–34.9) per 1,000 persons in England, and 9.83 (95% CI 7.66–12.61) in Sweden. In England, we observed a decrease from 2014 to 2018 in the utilization of this procedure in the 4 years preceding a TKR. The prevalence of all analyzed surgeries was consistently lower in controls. Conclusion There are comparable trends in the use of knee surgery in the years preceding TKR across England and Sweden. Of note, meniscal surgeries remain common, even within the year prior to TKR, highlighting that these patients may experience low-value care. Careful consideration of knee surgery in those with late-stage disease is required.

@article{brown_clinical_2023,
	title = {Clinical, patient-reported, radiographic and magnetic resonance imaging findings 11 years after acute posterior cruciate ligament injury treated non-surgically},
	volume = {24},
	issn = {1471-2474},
	url = {https://doi.org/10.1186/s12891-023-06480-0},
	doi = {10.1186/s12891-023-06480-0},
	abstract = {Long-term consequences of posterior cruciate ligament (PCL) injury such as persistent posterior tibial translation and risk of osteoarthritis development are unclear. Additionally, little data is available describing the natural history of structural morphology of the ruptured PCL. The purpose of the study was to determine the long-term outcome after non-operatively treated PCL injury.},
	number = {1},
	urldate = {2023-06-07},
	journal = {BMC Musculoskeletal Disorders},
	author = {Brown, Jamie S. and Mogianos, Krister and Roemer, Frank W. and Isacsson, Anders and Kumm, Jaanika and Frobell, Richard and Olsson, Ola and Englund, Martin},
	month = may,
	year = {2023},
	note = {Number: 1},
	keywords = {Long-term outcome, Non-surgical treatment, Posterior cruciate ligament},
	pages = {365},
}

Long-term consequences of posterior cruciate ligament (PCL) injury such as persistent posterior tibial translation and risk of osteoarthritis development are unclear. Additionally, little data is available describing the natural history of structural morphology of the ruptured PCL. The purpose of the study was to determine the long-term outcome after non-operatively treated PCL injury.

@article{emin_imaging-based_2023,
	title = {Imaging-based assessment of fatty acid composition in human bone marrow adipose tissue at 7 {T}: {Method} comparison and in vivo feasibility},
	volume = {90},
	copyright = {© 2023 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.},
	issn = {1522-2594},
	shorttitle = {Imaging-based assessment of fatty acid composition in human bone marrow adipose tissue at 7 {T}},
	url = {https://onlinelibrary.wiley.com/doi/abs/10.1002/mrm.29623},
	doi = {10.1002/mrm.29623},
	abstract = {Purpose To demonstrate the feasibility and accuracy of chemical shift–encoded imaging of the fatty acid composition (FAC) of human bone marrow adipose tissue at 7 T, and to determine suitable image-acquisition parameters using simulations. Methods The noise performance of FAC estimation was investigated using simulations with a range of inter-echo time, and accuracy was assessed using a phantom experiment. Furthermore, one knee of 8 knee-healthy subjects (ages 35–54 years) was imaged, and the fractions of saturated fatty acids (SFA) and polyunsaturated fatty acids (PUFA) were mapped. Values were compared between reconstruction methods, and between anatomical regions. Results Based on simulations, ΔTE = 0.6 ms was chosen. The phantom experiment demonstrated high accuracy of especially SFA using a constrained reconstruction model (slope = 1.1, average bias = −0.2\%). The lowest accuracy was seen for PUFA using a free model (slope = 2.0, average bias = 9.0\%). For in vivo images, the constrained model resulted in lower intersubject variation compared with the free model (e.g., in the femoral shaft, the SFA percent-point range was within 1.0\% [vs. 3.0\%]). Furthermore, significant regional FAC differences were detected. For example, using the constrained approach, the femoral SFA in the medial condyle was lower compared with the shaft (median [range]: 27.9\% [27.1\%, 28.4\%] vs. 32.5\% [31.8\%, 32.8\%]). Conclusion Bone marrow adipose tissue FAC quantification using chemical-shift encoding is feasible at 7 T. Both the noise performance and accuracy of the technique are superior using a constrained signal model.},
	language = {en},
	number = {1},
	urldate = {2023-03-28},
	journal = {Magnetic Resonance in Medicine},
	author = {Emin, Sevgi and Oei, Edwin H. G. and Englund, Martin and Peterson, Pernilla},
	month = feb,
	year = {2023},
	note = {Number: 1
\_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/mrm.29623},
	keywords = {7 T, MRI, bone marrow adipose tissue, chemical shift–encoded imaging, fatty acid composition},
	pages = {240--249},
}

Purpose To demonstrate the feasibility and accuracy of chemical shift–encoded imaging of the fatty acid composition (FAC) of human bone marrow adipose tissue at 7 T, and to determine suitable image-acquisition parameters using simulations. Methods The noise performance of FAC estimation was investigated using simulations with a range of inter-echo time, and accuracy was assessed using a phantom experiment. Furthermore, one knee of 8 knee-healthy subjects (ages 35–54 years) was imaged, and the fractions of saturated fatty acids (SFA) and polyunsaturated fatty acids (PUFA) were mapped. Values were compared between reconstruction methods, and between anatomical regions. Results Based on simulations, ΔTE = 0.6 ms was chosen. The phantom experiment demonstrated high accuracy of especially SFA using a constrained reconstruction model (slope = 1.1, average bias = −0.2%). The lowest accuracy was seen for PUFA using a free model (slope = 2.0, average bias = 9.0%). For in vivo images, the constrained model resulted in lower intersubject variation compared with the free model (e.g., in the femoral shaft, the SFA percent-point range was within 1.0% [vs. 3.0%]). Furthermore, significant regional FAC differences were detected. For example, using the constrained approach, the femoral SFA in the medial condyle was lower compared with the shaft (median [range]: 27.9% [27.1%, 28.4%] vs. 32.5% [31.8%, 32.8%]). Conclusion Bone marrow adipose tissue FAC quantification using chemical-shift encoding is feasible at 7 T. Both the noise performance and accuracy of the technique are superior using a constrained signal model.

@article{boric-persson_sick_2023,
	title = {Sick leave after arthroscopic meniscus repair vs. arthroscopic partial meniscectomy},
	volume = {5},
	issn = {2665-9131},
	url = {https://www.sciencedirect.com/science/article/pii/S2665913123000079},
	doi = {10.1016/j.ocarto.2023.100340},
	abstract = {Objective
To evaluate sick leave after meniscal repair vs arthroscopic partial meniscectomy (APM) and, for comparison, vs the general population.
Method
Using Swedish register data we included all employed persons aged 19–49 years in the general population of Skåne region and identified those having had meniscus repair or APM in the period of 2005–2012. We retrieved data on sick leave during 1 year before until 2 years after surgery. We used logistic regression to estimate the risk differences of being on sick leave and negative binomial model to analyze differences in the number of days on sick leave.
Results
We included 192 persons with meniscus repair, 2481 with APM, and 376 ​345 references without meniscus surgery. Of these, 55\% of meniscus repair group, 43\% of APM group had any sick leave in the 2-year period following the surgery, while 17\% of the references were on sick leave in the corresponding period. The mean (SD) number of days of sick leave after meniscus repair was 55 (77) days and for APM 37 (86) days. Meniscus repair was associated with higher probability of sick leave compared to APM with an adjusted risk difference of 0.13 (95\% CI 0.07–0.19).
Conclusion
Persons undergoing meniscus repair have more frequent and 37\% longer periods of sick leave in the short term than persons undergoing APM. However, sick leave in the long-term warrant further attention as successful repair may be associated with less knee osteoarthritis development than APM.},
	language = {en},
	number = {1},
	urldate = {2023-03-06},
	journal = {Osteoarthritis and Cartilage Open},
	author = {Boric-Persson, Fredrik and Turkiewicz, Aleksandra and Neuman, Paul and Englund, Martin},
	month = mar,
	year = {2023},
	note = {Number: 1},
	keywords = {Arthroscopy, Meniscus, Meniscus repair, Partial meniscectomy, Sick leave},
	pages = {100340},
}

Objective To evaluate sick leave after meniscal repair vs arthroscopic partial meniscectomy (APM) and, for comparison, vs the general population. Method Using Swedish register data we included all employed persons aged 19–49 years in the general population of Skåne region and identified those having had meniscus repair or APM in the period of 2005–2012. We retrieved data on sick leave during 1 year before until 2 years after surgery. We used logistic regression to estimate the risk differences of being on sick leave and negative binomial model to analyze differences in the number of days on sick leave. Results We included 192 persons with meniscus repair, 2481 with APM, and 376 ​345 references without meniscus surgery. Of these, 55% of meniscus repair group, 43% of APM group had any sick leave in the 2-year period following the surgery, while 17% of the references were on sick leave in the corresponding period. The mean (SD) number of days of sick leave after meniscus repair was 55 (77) days and for APM 37 (86) days. Meniscus repair was associated with higher probability of sick leave compared to APM with an adjusted risk difference of 0.13 (95% CI 0.07–0.19). Conclusion Persons undergoing meniscus repair have more frequent and 37% longer periods of sick leave in the short term than persons undergoing APM. However, sick leave in the long-term warrant further attention as successful repair may be associated with less knee osteoarthritis development than APM.

@article{rathmann_stable_2023,
	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},
	author = {Rathmann, Jens and Segelmark, Mårten and Englund, Martin and Mohammad, Aladdin J.},
	month = mar,
	year = {2023},
	pmid = {36894194},
	note = {Number: 1
Publisher: BMJ Specialist Journals
Section: Epidemiology},
	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{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},
	pmid = {37004213},
	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{ryden_human_2023,
	title = {A human meniscus explant model for studying early events in osteoarthritis development by proteomics},
	volume = {41},
	copyright = {© 2023 The Authors. Journal of Orthopaedic Research ® published by Wiley Periodicals LLC on behalf of Orthopaedic Research Society.},
	issn = {1554-527X},
	url = {https://onlinelibrary.wiley.com/doi/abs/10.1002/jor.25633},
	doi = {10.1002/jor.25633},
	abstract = {Degenerative meniscus lesions have been associated with both osteoarthritis etiology and its progression. We, therefore, sought to establish a human meniscus ex vivo model to study the meniscal response to cytokine treatment using a proteomics approach. Lateral menisci were obtained from five knee-healthy donors. The meniscal body was cut into vertical slices and further divided into an inner (avascular) and outer region. Explants were either left untreated (controls) or stimulated with cytokines. Medium changes were conducted every 3 days up to Day 21 and liquid chromatography–mass spectrometry was performed at all the time points for the identification and quantification of proteins. Mixed-effect linear regression models were used for statistical analysis to estimate the effect of treatments versus control on protein abundance. Treatment by IL1ß increased release of cytokines such as interleukins, chemokines, and matrix metalloproteinases but a limited catabolic effect in healthy human menisci explants. Further, we observed an increased release of matrix proteins (collagens, integrins, prolargin, tenascin) in response to oncostatin M (OSM) + tumor necrosis factor (TNF) and TNF+interleukin-6 (IL6) + sIL6R treatments, and analysis of semitryptic peptides provided additional evidence of increased catabolic effects in response to these treatments. The induced activation of catabolic processes may play a role in osteoarthritis development.},
	language = {en},
	number = {12},
	urldate = {2023-06-07},
	journal = {Journal of Orthopaedic Research},
	author = {Rydén, Martin and Lindblom, Karin and Yifter-Lindgren, Aida and Turkiewicz, Aleksandra and Aspberg, Anders and Tillgren, Viveka and Englund, Martin and Önnerfjord, Patrik},
	month = may,
	year = {2023},
	note = {\_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/jor.25633},
	keywords = {cytokines, explants, meniscus, osteoarthritis, proteomics},
	pages = {2765--2778},
}

Degenerative meniscus lesions have been associated with both osteoarthritis etiology and its progression. We, therefore, sought to establish a human meniscus ex vivo model to study the meniscal response to cytokine treatment using a proteomics approach. Lateral menisci were obtained from five knee-healthy donors. The meniscal body was cut into vertical slices and further divided into an inner (avascular) and outer region. Explants were either left untreated (controls) or stimulated with cytokines. Medium changes were conducted every 3 days up to Day 21 and liquid chromatography–mass spectrometry was performed at all the time points for the identification and quantification of proteins. Mixed-effect linear regression models were used for statistical analysis to estimate the effect of treatments versus control on protein abundance. Treatment by IL1ß increased release of cytokines such as interleukins, chemokines, and matrix metalloproteinases but a limited catabolic effect in healthy human menisci explants. Further, we observed an increased release of matrix proteins (collagens, integrins, prolargin, tenascin) in response to oncostatin M (OSM) + tumor necrosis factor (TNF) and TNF+interleukin-6 (IL6) + sIL6R treatments, and analysis of semitryptic peptides provided additional evidence of increased catabolic effects in response to these treatments. The induced activation of catabolic processes may play a role in osteoarthritis development.

@article{velek_changes_2023,
	title = {Changes to consultations and diagnosis of osteoarthritis in primary care during the {COVID}-19 pandemic},
	volume = {31},
	issn = {1063-4584},
	url = {https://www.sciencedirect.com/science/article/pii/S1063458423006994},
	doi = {10.1016/j.joca.2023.02.075},
	abstract = {Objective
General practitioners (GP) are often the first medical professionals to treat musculoskeletal complaints. Yet the impact of COVID-19 on primary care utilisation for musculoskeletal complaints is largely unknown. This study quantifies the impact of the pandemic on primary care utilisation for musculoskeletal complaints and specifically osteoarthritis (OA) in the Netherlands.
Design
We extracted data on GP consultations in 2015–2020 from 118,756 patients over 45 years of age and estimated reductions in consultations in 2020 as compared to 5-year average. Outcomes were GP consultations for: any musculoskeletal complaints, knee and hip OA, knee and hip complaints, and newly diagnosed knee and hip OA/complaints.
Results
The relative reductions in consultations ranged from 46.7\% (95\% confidence intervals (CI): 43.9–49.3\%) (all musculoskeletal consultations) to 61.6\% (95\% CI: 44.7–73.3\%) (hip complaints) at the peak of the first wave, and from 9.3\% (95\% CI: 5.7–12.7\%) (all musculoskeletal consultations) to 26.6\% (95\% CI: 11.5–39.1\%) (knee OA) at the peak of the second wave. The reductions for new diagnoses were 87.0\% (95\% CI: 71.5–94.1\%) for knee OA/complaints, and 70.5\% (95\% CI: 37.7–86.0\%) for hip OA/complaints at the peak of the first wave, and not statistically significant at the peak of the second wave.
Conclusion
We observed 47\% reduction in GP consultations for musculoskeletal disorders during the first wave and 9\% during the second wave. For hip and knee OA/complaints, the reductions were over 50\% during the first, and 10\% during the second wave. This disruption may lead to accumulation of patients with severe OA symptoms and more requests for arthroplasty surgery.},
	language = {en},
	number = {6},
	urldate = {2023-06-07},
	journal = {Osteoarthritis and Cartilage},
	author = {Velek, P. and de Schepper, E. and Schiphof, D. and Evert van Spil, W. and Englund, M. and Magnusson, K. and Kiadaliri, A. and Dell'Isola, A. and Licher, S. and Bierma-Zeinstra, S. and Runhaar, J.},
	month = jun,
	year = {2023},
	note = {Number: 6},
	keywords = {COVID-19, Healthcare utilisation, Musculoskeletal disorders, Osteoarthritis, Primary care},
	pages = {829--838},
}

Objective General practitioners (GP) are often the first medical professionals to treat musculoskeletal complaints. Yet the impact of COVID-19 on primary care utilisation for musculoskeletal complaints is largely unknown. This study quantifies the impact of the pandemic on primary care utilisation for musculoskeletal complaints and specifically osteoarthritis (OA) in the Netherlands. Design We extracted data on GP consultations in 2015–2020 from 118,756 patients over 45 years of age and estimated reductions in consultations in 2020 as compared to 5-year average. Outcomes were GP consultations for: any musculoskeletal complaints, knee and hip OA, knee and hip complaints, and newly diagnosed knee and hip OA/complaints. Results The relative reductions in consultations ranged from 46.7% (95% confidence intervals (CI): 43.9–49.3%) (all musculoskeletal consultations) to 61.6% (95% CI: 44.7–73.3%) (hip complaints) at the peak of the first wave, and from 9.3% (95% CI: 5.7–12.7%) (all musculoskeletal consultations) to 26.6% (95% CI: 11.5–39.1%) (knee OA) at the peak of the second wave. The reductions for new diagnoses were 87.0% (95% CI: 71.5–94.1%) for knee OA/complaints, and 70.5% (95% CI: 37.7–86.0%) for hip OA/complaints at the peak of the first wave, and not statistically significant at the peak of the second wave. Conclusion We observed 47% reduction in GP consultations for musculoskeletal disorders during the first wave and 9% during the second wave. For hip and knee OA/complaints, the reductions were over 50% during the first, and 10% during the second wave. This disruption may lead to accumulation of patients with severe OA symptoms and more requests for arthroplasty surgery.

@article{battista_factors_2023,
	title = {Factors associated with adherence to a supervised exercise intervention for osteoarthritis: {Data} from the swedish osteoarthritis registry},
	volume = {75},
	issn = {2151-464X, 2151-4658},
	shorttitle = {Factors {Associated} {With} {Adherence} to a {Supervised} {Exercise} {Intervention} for {Osteoarthritis}},
	url = {https://onlinelibrary.wiley.com/doi/10.1002/acr.25135},
	doi = {10.1002/acr.25135},
	abstract = {Objective. To explore how lifestyle and demographic, socioeconomic, and disease-related factors are associated with supervised exercise adherence in an osteoarthritis (OA) management program and the ability of these factors to explain exercise adherence.
Methods. A cohort register-based study on participants from the Swedish Osteoarthritis Registry who attended the exercise part of a nationwide Swedish OA management program. We ran a multinomial logistic regression to determine the association of exercise adherence with the abovementioned factors. We calculated their ability to explain exercise adherence with the McFadden R2.
Results. Our sample comprises 19,750 participants (73\% female, mean ± SD age 67 ± 8.9 years). Among them, 5,862 (30\%) reached a low level of adherence, 3,947 (20\%) a medium level, and 9,941 (50\%) a high level. After a listwise deletion, the analysis was run on 16,685 participants (85\%), with low levels of adherence as the reference category. Some factors were positively associated with high levels of adherence, such as older age (relative risk ratio [RRR] 1.01 [95\% confidence interval (95\% CI) 1.01–1.02] per year), and the arthritis-specific self-efficacy (RRR 1.04 [95\% CI 1.02–1.07] per 10-point increase). Others were negatively associated with high levels of adherence, such as female sex (RRR 0.82 [95\% CI 0.75–0.89]), having a medium (RRR 0.89 [95\% CI 0.81–0.98] or a high level of education (RRR 0.84 [95\% CI 0.76–0.94]). Nevertheless, the investigating factors could explain 1\% of the variability in exercise adherence (R2 = 0.012).
Conclusion. Despite the associations reported above, the poorly explained variability suggests that strategies based on lifestyle and demographic, socioeconomic, and disease-related factors are unlikely to improve exercise adherence significantly.},
	language = {en},
	number = {10},
	urldate = {2023-06-07},
	journal = {Arthritis Care \& Research},
	author = {Battista, Simone and Kiadaliri, Ali and Jönsson, Thérése and Gustafsson, Kristin and Englund, Martin and Testa, Marco and Dell'Isola, Andrea},
	month = may,
	year = {2023},
	pages = {2117--2126},
}

Objective. To explore how lifestyle and demographic, socioeconomic, and disease-related factors are associated with supervised exercise adherence in an osteoarthritis (OA) management program and the ability of these factors to explain exercise adherence. Methods. A cohort register-based study on participants from the Swedish Osteoarthritis Registry who attended the exercise part of a nationwide Swedish OA management program. We ran a multinomial logistic regression to determine the association of exercise adherence with the abovementioned factors. We calculated their ability to explain exercise adherence with the McFadden R2. Results. Our sample comprises 19,750 participants (73% female, mean ± SD age 67 ± 8.9 years). Among them, 5,862 (30%) reached a low level of adherence, 3,947 (20%) a medium level, and 9,941 (50%) a high level. After a listwise deletion, the analysis was run on 16,685 participants (85%), with low levels of adherence as the reference category. Some factors were positively associated with high levels of adherence, such as older age (relative risk ratio [RRR] 1.01 [95% confidence interval (95% CI) 1.01–1.02] per year), and the arthritis-specific self-efficacy (RRR 1.04 [95% CI 1.02–1.07] per 10-point increase). Others were negatively associated with high levels of adherence, such as female sex (RRR 0.82 [95% CI 0.75–0.89]), having a medium (RRR 0.89 [95% CI 0.81–0.98] or a high level of education (RRR 0.84 [95% CI 0.76–0.94]). Nevertheless, the investigating factors could explain 1% of the variability in exercise adherence (R2 = 0.012). Conclusion. Despite the associations reported above, the poorly explained variability suggests that strategies based on lifestyle and demographic, socioeconomic, and disease-related factors are unlikely to improve exercise adherence significantly.

@article{ryden_identification_2023,
	title = {Identification and quantification of degradome components in human synovial fluid reveals an increased proteolytic activity in knee osteoarthritis patients vs controls},
	volume = {23},
	issn = {1615-9861},
	url = {https://onlinelibrary.wiley.com/doi/abs/10.1002/pmic.202300040},
	doi = {10.1002/pmic.202300040},
	abstract = {Synovial fluid (SF) may contain cleavage products of proteolytic activities. Our aim was to characterize the degradome through analysis of proteolytic activity and differential abundance of these components in a peptidomic analysis of SF in knee osteoarthritis (OA) patients versus controls (n = 23). SF samples from end-stage knee osteoarthritis patients undergoing total knee replacement surgery and controls, that is, deceased donors without known knee disease were previously run using liquid chromatography mass spectrometry (LC-MS). This data was used to perform new database searches generating results for non-tryptic and semi-tryptic peptides for studies of degradomics in OA. We used linear mixed models to estimate differences in peptide-level expression between the two groups. Known proteolytic events (from the MEROPS peptidase database) were mapped to the dataset, allowing the identification of potential proteases and which substrates they cleave. We also developed a peptide-centric R tool, proteasy, which facilitates analyses that involve retrieval and mapping of proteolytic events. We identified 429 differentially abundant peptides. We found that the increased abundance of cleaved APOA1 peptides is likely a consequence of enzymatic degradation by metalloproteinases and chymase. We identified metalloproteinase, chymase, and cathepsins as the main proteolytic actors. The analysis indicated increased activity of these proteases irrespective of their abundance.},
	language = {en},
	number = {15},
	urldate = {2023-05-29},
	journal = {Proteomics},
	author = {Rydén, Martin and Turkiewicz, Aleksandra and Önnerfjord, Patrik and Tjörnstrand, Jon and Englund, Martin and Ali, Neserin},
	month = may,
	year = {2023},
	note = {Number: 15
\_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/pmic.202300040},
	keywords = {degradomics, osteoarthritis, peptidomics, proteomics, synovial fluid},
	pages = {2300040},
}

Synovial fluid (SF) may contain cleavage products of proteolytic activities. Our aim was to characterize the degradome through analysis of proteolytic activity and differential abundance of these components in a peptidomic analysis of SF in knee osteoarthritis (OA) patients versus controls (n = 23). SF samples from end-stage knee osteoarthritis patients undergoing total knee replacement surgery and controls, that is, deceased donors without known knee disease were previously run using liquid chromatography mass spectrometry (LC-MS). This data was used to perform new database searches generating results for non-tryptic and semi-tryptic peptides for studies of degradomics in OA. We used linear mixed models to estimate differences in peptide-level expression between the two groups. Known proteolytic events (from the MEROPS peptidase database) were mapped to the dataset, allowing the identification of potential proteases and which substrates they cleave. We also developed a peptide-centric R tool, proteasy, which facilitates analyses that involve retrieval and mapping of proteolytic events. We identified 429 differentially abundant peptides. We found that the increased abundance of cleaved APOA1 peptides is likely a consequence of enzymatic degradation by metalloproteinases and chymase. We identified metalloproteinase, chymase, and cathepsins as the main proteolytic actors. The analysis indicated increased activity of these proteases irrespective of their abundance.

@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},
	pmid = {37347073},
	pmcid = {PMC10281277},
	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},
	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},
	note = {Publisher: Nature Publishing Group},
	keywords = {Medical research, Molecular biology, Neuroscience, Social sciences},
	pages = {755--756},
}

@article{kamps_comorbidity_2023,
	title = {Comorbidity in incident osteoarthritis cases and matched controls using electronic health record data},
	volume = {25},
	issn = {1478-6362},
	url = {https://doi.org/10.1186/s13075-023-03086-8},
	doi = {10.1186/s13075-023-03086-8},
	abstract = {Comorbidities are common in patients with osteoarthritis (OA). This study aimed to determine the association of a wide range of previously diagnosed comorbidities in adults with newly diagnosed OA compared with matched controls without OA.},
	number = {1},
	urldate = {2023-08-09},
	journal = {Arthritis Research \& Therapy},
	author = {Kamps, Anne and Runhaar, Jos and de Ridder, Maria A. J. and de Wilde, Marcel and van der Lei, Johan and Zhang, Weiya and Prieto-Alhambra, Daniel and Englund, Martin and de Schepper, Evelien I. T. and Bierma-Zeinstra, Sita M. A.},
	month = jul,
	year = {2023},
	note = {Number: 1},
	keywords = {Comorbidity, Epidemiology, Osteoarthritis, Primary Care},
	pages = {114},
}

Comorbidities are common in patients with osteoarthritis (OA). This study aimed to determine the association of a wide range of previously diagnosed comorbidities in adults with newly diagnosed OA compared with matched controls without OA.

@article{dellisola_use_2023,
	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},
	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},
	pmid = {37739449},
	note = {Publisher: BMJ Specialist Journals
Section: Osteoarthritis},
	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},
	pmid = {36688706},
	pmcid = {PMC10629784},
	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{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},
	pmid = {37622647},
	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{jahangir_sensitivity_2023,
	title = {Sensitivity of simulated knee joint mechanics to selected human and bovine fibril-reinforced poroelastic material properties},
	volume = {160},
	issn = {0021-9290},
	url = {https://www.sciencedirect.com/science/article/pii/S0021929023003718},
	doi = {10.1016/j.jbiomech.2023.111800},
	abstract = {Fibril-reinforced poroviscoelastic material models are considered state-of-the-art in modeling articular cartilage biomechanics. Yet, cartilage material parameters are often based on bovine tissue properties in computational knee joint models, although bovine properties are distinctly different from those of humans. Thus, we aimed to investigate how cartilage mechanical responses are affected in the knee joint model during walking when fibril-reinforced poroviscoelastic properties of cartilage are based on human data instead of bovine. We constructed a finite element knee joint model in which tibial and femoral cartilages were modeled as fibril-reinforced poroviscoelastic material using either human or bovine data. Joint loading was based on subject-specific gait data. The resulting mechanical responses of knee cartilage were compared between the knee joint models with human or bovine fibril-reinforced poroviscoelastic cartilage properties. Furthermore, we conducted a sensitivity analysis to determine which fibril-reinforced poroviscoelastic material parameters have the greatest impact on cartilage mechanical responses in the knee joint during walking. In general, bovine cartilage properties yielded greater maximum principal stresses and fluid pressures (both up to 30\%) when compared to the human cartilage properties during the loading response in both femoral and tibial cartilage sites. Cartilage mechanical responses were very sensitive to the collagen fibril-related material parameter variations during walking while they were unresponsive to proteoglycan matrix or fluid flow-related material parameter variations. Taken together, human cartilage material properties should be accounted for when the goal is to compare absolute mechanical responses of knee joint cartilage as bovine material parameters lead to substantially different cartilage mechanical responses.},
	urldate = {2023-11-08},
	journal = {Journal of Biomechanics},
	author = {Jahangir, Sana and Esrafilian, Amir and Ebrahimi, Mohammadhossein and Stenroth, Lauri and Alkjær, Tine and Henriksen, Marius and Englund, Martin and Mononen, Mika E. and Korhonen, Rami K. and Tanska, Petri},
	month = nov,
	year = {2023},
	keywords = {Articular cartilage, Fibril-reinforced poroelastic, Finite element modeling, Knee joint, Material properties},
	pages = {111800},
}

Fibril-reinforced poroviscoelastic material models are considered state-of-the-art in modeling articular cartilage biomechanics. Yet, cartilage material parameters are often based on bovine tissue properties in computational knee joint models, although bovine properties are distinctly different from those of humans. Thus, we aimed to investigate how cartilage mechanical responses are affected in the knee joint model during walking when fibril-reinforced poroviscoelastic properties of cartilage are based on human data instead of bovine. We constructed a finite element knee joint model in which tibial and femoral cartilages were modeled as fibril-reinforced poroviscoelastic material using either human or bovine data. Joint loading was based on subject-specific gait data. The resulting mechanical responses of knee cartilage were compared between the knee joint models with human or bovine fibril-reinforced poroviscoelastic cartilage properties. Furthermore, we conducted a sensitivity analysis to determine which fibril-reinforced poroviscoelastic material parameters have the greatest impact on cartilage mechanical responses in the knee joint during walking. In general, bovine cartilage properties yielded greater maximum principal stresses and fluid pressures (both up to 30%) when compared to the human cartilage properties during the loading response in both femoral and tibial cartilage sites. Cartilage mechanical responses were very sensitive to the collagen fibril-related material parameter variations during walking while they were unresponsive to proteoglycan matrix or fluid flow-related material parameter variations. Taken together, human cartilage material properties should be accounted for when the goal is to compare absolute mechanical responses of knee joint cartilage as bovine material parameters lead to substantially different cartilage mechanical responses.

@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},
	pmid = {38037388},
	pmcid = {PMC10690978},
	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,
	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},
	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},
	pmid = {37879858},
	note = {Publisher: BMJ Publishing Group Ltd and British Association of Sport and Exercise Medicine
Section: Original research},
	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{paz-gonzalez_proteomic_2023,
	title = {Proteomic profiling of human menisci from mild joint degeneration and end-stage osteoarthritis versus healthy controls},
	volume = {5},
	issn = {2665-9131},
	url = {https://www.sciencedirect.com/science/article/pii/S2665913123000845},
	doi = {10.1016/j.ocarto.2023.100417},
	abstract = {Objective
To gain new insight into the molecular changes of the meniscus by comparing the proteome profiles of healthy controls with mild degeneration and end-stage osteoarthritis (OA).
Method
We obtained tissue plugs from lateral and medial menisci of 37 individuals (central part of the posterior horn) classified as healthy (n ​= ​12), mild signs of joint damage (n ​= ​13) and end-stage OA (n ​= ​12). The protein profile was analysed by nano-liquid chromatography-mass spectrometry using data-independent acquisition and quantified by Spectronaut. Linear-mixed effects modelling was applied to extract the between-group comparisons.
Results
A similar protein profile was observed for the mild group as compared to healthy controls while the most different group was end-stage OA mainly for the medial compartment. When a pattern of gradual change in protein levels from healthy to end-stage OA was required, a 42-proteins panel was identified, suggesting a potential role in OA development. The levels of QSOX1 were lower and G6PD higher in the mild group following the proposed protein abundance pattern. Qualitative protein changes suggest lower levels of CYTL1 as a potential biomarker of early joint degradation.
Conclusion
For future targeted proteomic approaches, we propose a candidate panel of 42 proteins based on gradually altered meniscal posterior horn protein abundance patterns associated with joint degradation.},
	number = {4},
	urldate = {2024-03-06},
	journal = {Osteoarthritis and Cartilage Open},
	author = {Paz-González, Rocío and Turkiewicz, Aleksandra and Ali, Neserin and Ruiz-Romero, Cristina and Blanco, Francisco J. and Englund, Martin and Önnerfjord, Patrik},
	month = dec,
	year = {2023},
	keywords = {Degeneration, Meniscus, Osteoarthritis, Proteomics},
	pages = {100417},
}

Objective To gain new insight into the molecular changes of the meniscus by comparing the proteome profiles of healthy controls with mild degeneration and end-stage osteoarthritis (OA). Method We obtained tissue plugs from lateral and medial menisci of 37 individuals (central part of the posterior horn) classified as healthy (n ​= ​12), mild signs of joint damage (n ​= ​13) and end-stage OA (n ​= ​12). The protein profile was analysed by nano-liquid chromatography-mass spectrometry using data-independent acquisition and quantified by Spectronaut. Linear-mixed effects modelling was applied to extract the between-group comparisons. Results A similar protein profile was observed for the mild group as compared to healthy controls while the most different group was end-stage OA mainly for the medial compartment. When a pattern of gradual change in protein levels from healthy to end-stage OA was required, a 42-proteins panel was identified, suggesting a potential role in OA development. The levels of QSOX1 were lower and G6PD higher in the mild group following the proposed protein abundance pattern. Qualitative protein changes suggest lower levels of CYTL1 as a potential biomarker of early joint degradation. Conclusion For future targeted proteomic approaches, we propose a candidate panel of 42 proteins based on gradually altered meniscal posterior horn protein abundance patterns associated with joint degradation.

@article{battista_giving_2022,
	title = {Giving an account of patients' experience: {A} qualitative study on the care process of hip and knee osteoarthritis},
	volume = {25},
	issn = {1369-7625},
	shorttitle = {Giving an account of patients' experience},
	url = {https://doi.org/10.1111/hex.13468},
	doi = {10.1111/hex.13468},
	abstract = {INTRODUCTION: Despite the publication of clinical practice guidelines, the quality of the care process as experienced by patients with osteoarthritis (OA) appears suboptimal. Hence, this study investigates how patients with OA experience their disease and care process, highlighting potential elements that can enhance or spoil it, to optimise their quality of care.
METHODS: A qualitative study based on semi-structured interviews. Patients with hip and knee OA in Italy were interviewed. The interview guide was created by a pool of health professionals and patients. The interviews were analysed through a theme-based analysis following a philosophy of descriptive phenomenological research.
RESULTS: Our analysis revealed seven main themes: (1) Experiencing a sense of uncertainty, as interviewees perceived treatment choices not to be based on medical evidence; (2) Establishing challenging relationships with the self and the other, as they did not feel understood and felt ashamed or hopeless about their condition; (3) Being stuck in one's own or the health professionals' beliefs about the disease management, as a common thought was the perception of movement as something dangerous together with a frequent prescription of passive therapies; (4) Dealing with one's own attitudes towards the disease; Understanding (5) the barriers to and (6) the facilitators of the adherence to therapeutic exercise, which revolve around the therapy cost, the time needed and the patients' willingness to change their life habits and (7) Developing an uneasy relationship with food since the diet was considered as something that "you force yourself to follow" and overeating as a way "to eat your feelings".
CONCLUSION: The lack of clear explanations and a negative attitude towards first-line nonsurgical treatments (mainly physical exercise), which are considered as a way to fill the time while waiting for surgery, underlines the importance of providing patients with adequate information about OA treatments and to better explain the role of first-line intervention in the care of OA. This will enhance patient-centred and shared decision-making treatments.
PATIENT CONTRIBUTION: Patients with hip and knee OA participated in creating the interview and contributed with their experience of their care process.},
	language = {eng},
	number = {3},
	journal = {Health Expectations: An International Journal of Public Participation in Health Care and Health Policy},
	author = {Battista, Simone and Manoni, Mattia and Dell'Isola, Andrea and Englund, Martin and Palese, Alvisa and Testa, Marco},
	month = mar,
	year = {2022},
	pmid = {35266257},
	note = {Number: 3},
	keywords = {clinical governance, osteoarthritis, phenomenology, physical therapists, physical therapy specialty, policy making, practice guidelines as topic},
	pages = {1140--1156},
}

INTRODUCTION: Despite the publication of clinical practice guidelines, the quality of the care process as experienced by patients with osteoarthritis (OA) appears suboptimal. Hence, this study investigates how patients with OA experience their disease and care process, highlighting potential elements that can enhance or spoil it, to optimise their quality of care. METHODS: A qualitative study based on semi-structured interviews. Patients with hip and knee OA in Italy were interviewed. The interview guide was created by a pool of health professionals and patients. The interviews were analysed through a theme-based analysis following a philosophy of descriptive phenomenological research. RESULTS: Our analysis revealed seven main themes: (1) Experiencing a sense of uncertainty, as interviewees perceived treatment choices not to be based on medical evidence; (2) Establishing challenging relationships with the self and the other, as they did not feel understood and felt ashamed or hopeless about their condition; (3) Being stuck in one's own or the health professionals' beliefs about the disease management, as a common thought was the perception of movement as something dangerous together with a frequent prescription of passive therapies; (4) Dealing with one's own attitudes towards the disease; Understanding (5) the barriers to and (6) the facilitators of the adherence to therapeutic exercise, which revolve around the therapy cost, the time needed and the patients' willingness to change their life habits and (7) Developing an uneasy relationship with food since the diet was considered as something that "you force yourself to follow" and overeating as a way "to eat your feelings". CONCLUSION: The lack of clear explanations and a negative attitude towards first-line nonsurgical treatments (mainly physical exercise), which are considered as a way to fill the time while waiting for surgery, underlines the importance of providing patients with adequate information about OA treatments and to better explain the role of first-line intervention in the care of OA. This will enhance patient-centred and shared decision-making treatments. PATIENT CONTRIBUTION: Patients with hip and knee OA participated in creating the interview and contributed with their experience of their care process.

@article{swain_comorbidities_2022,
	title = {Comorbidities in osteoarthritis ({ComOA}): a combined cross-sectional, case–control and cohort study using large electronic health records in four {European} countries},
	volume = {12},
	copyright = {© Author(s) (or their employer(s)) 2022. 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 = {2044-6055, 2044-6055},
	shorttitle = {Comorbidities in osteoarthritis ({ComOA})},
	url = {https://bmjopen.bmj.com/content/12/4/e052816},
	doi = {10.1136/bmjopen-2021-052816},
	abstract = {Introduction Osteoarthritis (OA) is one of the leading chronic conditions in the older population. People with OA are more likely to have one or more other chronic conditions than those without. However, the temporal associations, clusters of the comorbidities, role of analgesics and the causality and variation between populations are yet to be investigated. This paper describes the protocol of a multinational study in four European countries (UK, Netherlands, Sweden and Spain) exploring comorbidities in people with OA.
Methods and analysis This multinational study will investigate (1) the temporal associations of 61 identified comorbidities with OA, (2) the clusters and trajectories of comorbidities in people with OA, (3) the role of analgesics on incidence of comorbidities in people with OA, (4) the potential biomarkers and causality between OA and the comorbidities, and (5) variations between countries.A combined case–control and cohort study will be conducted to find the temporal association of OA with the comorbidities using the national or regional health databases. Latent class analysis will be performed to identify the clusters at baseline and joint latent class analysis will be used to examine trajectories during the follow-up. A cohort study will be undertaken to evaluate the role of non-steroidal anti-inflammatory drugs (NSAIDs), opioids and paracetamol on the incidence of comorbidities. Mendelian randomisation will be performed to investigate the potential biomarkers for causality between OA and the comorbidities using the UK Biobank and the Rotterdam Study databases. Finally, a meta-analyses will be used to examine the variations and pool the results from different countries.
Ethics and dissemination Research ethics was obtained according to each database requirement. Results will be disseminated through the FOREUM website, scientific meetings, publications and in partnership with patient organisations.},
	language = {en},
	number = {4},
	urldate = {2022-04-21},
	journal = {BMJ Open},
	author = {Swain, Subhashisa and Kamps, Anne and Runhaar, Jos and Dell'Isola, Andrea and Turkiewicz, Aleksandra and Robinson, Danielle and Strauss, V. and Mallen, Christian and Kuo, Chang-Fu and Coupland, Carol and Doherty, Michael and Sarmanova, Aliya and Prieto-Alhambra, Daniel and Englund, Martin and Bierma-Zeinstra, Sita M. A. and Zhang, Weiya},
	month = apr,
	year = {2022},
	pmid = {35387809},
	note = {Number: 4
Publisher: British Medical Journal Publishing Group
Section: Rheumatology},
	keywords = {EPIDEMIOLOGY, Musculoskeletal disorders, RHEUMATOLOGY},
	pages = {e052816},
}

Introduction Osteoarthritis (OA) is one of the leading chronic conditions in the older population. People with OA are more likely to have one or more other chronic conditions than those without. However, the temporal associations, clusters of the comorbidities, role of analgesics and the causality and variation between populations are yet to be investigated. This paper describes the protocol of a multinational study in four European countries (UK, Netherlands, Sweden and Spain) exploring comorbidities in people with OA. Methods and analysis This multinational study will investigate (1) the temporal associations of 61 identified comorbidities with OA, (2) the clusters and trajectories of comorbidities in people with OA, (3) the role of analgesics on incidence of comorbidities in people with OA, (4) the potential biomarkers and causality between OA and the comorbidities, and (5) variations between countries.A combined case–control and cohort study will be conducted to find the temporal association of OA with the comorbidities using the national or regional health databases. Latent class analysis will be performed to identify the clusters at baseline and joint latent class analysis will be used to examine trajectories during the follow-up. A cohort study will be undertaken to evaluate the role of non-steroidal anti-inflammatory drugs (NSAIDs), opioids and paracetamol on the incidence of comorbidities. Mendelian randomisation will be performed to investigate the potential biomarkers for causality between OA and the comorbidities using the UK Biobank and the Rotterdam Study databases. Finally, a meta-analyses will be used to examine the variations and pool the results from different countries. Ethics and dissemination Research ethics was obtained according to each database requirement. Results will be disseminated through the FOREUM website, scientific meetings, publications and in partnership with patient organisations.

@article{casula_quantitative_2022,
	title = {Quantitative evaluation of the tibiofemoral joint cartilage by {T2} mapping in patients with acute anterior cruciate ligament injury vs contralateral knees: {Results} from the subacute phase using data from the {NACOX} study cohort},
	volume = {30},
	issn = {1522-9653},
	shorttitle = {Quantitative evaluation of the tibiofemoral joint cartilage by {T2} mapping in patients with acute anterior cruciate ligament injury vs contralateral knees},
	url = {https://doi.org/10.1016/j.joca.2022.02.623},
	doi = {10.1016/j.joca.2022.02.623},
	abstract = {OBJECTIVE: Immediate cartilage structural alterations in the acute phase after an anterior cruciate ligament (ACL) rupture may be a precursor to posttraumatic osteoarthritis (PTOA) development. Our aim was to describe changes in cartilage matrix in the subacute phase of the acutely ACL-injured knee compared to the contralateral uninjured knee.
DESIGN: Participants (n=118) aged 15-40 years with an acute ACL injury were consecutively included in subacute phase after acute ACL-injury and underwent MRI (mean 29 days post trauma) of both knees. Mean T2 relaxation times, T2 spatial coefficient of variation and cartilage thickness were determined for different regions of the tibiofemoral cartilage. Differences between the acutely ACL-injured and uninjured knee were evaluated using Wilcoxon signed-rank test.
RESULTS: T2 relaxation time in injured knees was increased in multiple cartilage regions from both medial and lateral compartment compared to contralateral knees, mostly in medial trochlea and posterior tibia (P-value{\textless}0.001). In the same sites of injured knees, we observed significantly thinner cartilage. Moreover, injured knees presented shorter T2 relaxation time in superficial cartilage on lateral central femur and trochlea (P-value{\textless}0.001), and decreased T2 spatial coefficient of variation in lateral trochlea and load bearing regions of medial-central femoral condyle and central tibia in both compartments.
CONCLUSION: Small but statistically significant differences were observed in the subacute phase between ACL-injured and uninjured knee in cartilage T2 relaxation time and cartilage thickness. Future longitudinal observations of the same cohort will allow for better understanding of early development of PTOA.
TRIAL REGISTRATION NUMBER: NCT02931084.},
	language = {eng},
	number = {7},
	journal = {Osteoarthritis and Cartilage},
	author = {Casula, Victor and Tajik, Bashir Edwardsson and Kvist, Joanna and Frobell, Richard and Haapea, Marianne and Nieminen, Miika T. and Gauffin, Håkan and Englund, Martin},
	month = apr,
	year = {2022},
	pmid = {35421548},
	keywords = {ACL, PTOA, T2-mapping},
	pages = {987--997},
}

OBJECTIVE: Immediate cartilage structural alterations in the acute phase after an anterior cruciate ligament (ACL) rupture may be a precursor to posttraumatic osteoarthritis (PTOA) development. Our aim was to describe changes in cartilage matrix in the subacute phase of the acutely ACL-injured knee compared to the contralateral uninjured knee. DESIGN: Participants (n=118) aged 15-40 years with an acute ACL injury were consecutively included in subacute phase after acute ACL-injury and underwent MRI (mean 29 days post trauma) of both knees. Mean T2 relaxation times, T2 spatial coefficient of variation and cartilage thickness were determined for different regions of the tibiofemoral cartilage. Differences between the acutely ACL-injured and uninjured knee were evaluated using Wilcoxon signed-rank test. RESULTS: T2 relaxation time in injured knees was increased in multiple cartilage regions from both medial and lateral compartment compared to contralateral knees, mostly in medial trochlea and posterior tibia (P-value\textless0.001). In the same sites of injured knees, we observed significantly thinner cartilage. Moreover, injured knees presented shorter T2 relaxation time in superficial cartilage on lateral central femur and trochlea (P-value\textless0.001), and decreased T2 spatial coefficient of variation in lateral trochlea and load bearing regions of medial-central femoral condyle and central tibia in both compartments. CONCLUSION: Small but statistically significant differences were observed in the subacute phase between ACL-injured and uninjured knee in cartilage T2 relaxation time and cartilage thickness. Future longitudinal observations of the same cohort will allow for better understanding of early development of PTOA. TRIAL REGISTRATION NUMBER: NCT02931084.

@article{stamatis_epidemiology_2022,
	title = {Epidemiology of biopsy-confirmed giant cell arteritis in southern {Sweden}—an update on incidence and first prevalence estimate},
	volume = {61},
	issn = {1462-0324},
	url = {https://doi.org/10.1093/rheumatology/keab269},
	doi = {10.1093/rheumatology/keab269},
	abstract = {To characterize the epidemiology of temporal artery biopsy-positive (TAB+) GCA, including trends in incidence, seasonal variation and prevalence in Skåne, the southernmost region of Sweden.All histopathology reports of TABs from 1997 through 2019 were reviewed to identify patients diagnosed with TAB+ GCA. Incidence rates based on the 23-year period and the point-prevalence at 31 December 2014 were determined. An alternative prevalence calculation included only TAB+ GCA patients living in the study area and receiving immunosuppressant therapy on the point-prevalence date.One thousand three hundred and sixty patients were diagnosed with TAB+ GCA (71\% female). The average annual incidence 1997–2019 was 13.3 (95\% CI: 12.6, 14.0) per 100 000 inhabitants aged ≥50 years and was higher in females (17.8; 95\% CI: 16.7, 18.9) than in males (8.2; 95\% CI: 7.4, 9.0). The age- and sex-standardized incidence declined from 17.3 in 1997 to 8.7 in 2019, with incidence ratio (IR) of 0.98 per year (95\% CI: 0.98, 0.99). A seasonal variation was observed with higher incidence during spring than winter [IR = 1.19 (95\% CI: 1.03, 1.39)]. The overall point-prevalence of TAB+ GCA was 127.1/100 000 (95\% CI: 117, 137.3) and was 75.5 (95\% CI: 67.7, 83.3) when including only patients receiving immunosuppressants.Over the past 2 decades, the incidence of biopsy-confirmed GCA has decreased by ∼2\% per year. Still, a high prevalence of GCA on current treatment was observed. More cases are diagnosed during spring and summer than in the winter.},
	number = {1},
	urldate = {2022-04-21},
	journal = {Rheumatology},
	author = {Stamatis, Pavlos and Turkiewicz, Aleksandra and Englund, Martin and Turesson, Carl and Mohammad, Aladdin J},
	month = jan,
	year = {2022},
	note = {Number: 1},
	pages = {146--153},
}

To characterize the epidemiology of temporal artery biopsy-positive (TAB+) GCA, including trends in incidence, seasonal variation and prevalence in Skåne, the southernmost region of Sweden.All histopathology reports of TABs from 1997 through 2019 were reviewed to identify patients diagnosed with TAB+ GCA. Incidence rates based on the 23-year period and the point-prevalence at 31 December 2014 were determined. An alternative prevalence calculation included only TAB+ GCA patients living in the study area and receiving immunosuppressant therapy on the point-prevalence date.One thousand three hundred and sixty patients were diagnosed with TAB+ GCA (71% female). The average annual incidence 1997–2019 was 13.3 (95% CI: 12.6, 14.0) per 100 000 inhabitants aged ≥50 years and was higher in females (17.8; 95% CI: 16.7, 18.9) than in males (8.2; 95% CI: 7.4, 9.0). The age- and sex-standardized incidence declined from 17.3 in 1997 to 8.7 in 2019, with incidence ratio (IR) of 0.98 per year (95% CI: 0.98, 0.99). A seasonal variation was observed with higher incidence during spring than winter [IR = 1.19 (95% CI: 1.03, 1.39)]. The overall point-prevalence of TAB+ GCA was 127.1/100 000 (95% CI: 117, 137.3) and was 75.5 (95% CI: 67.7, 83.3) when including only patients receiving immunosuppressants.Over the past 2 decades, the incidence of biopsy-confirmed GCA has decreased by ∼2% per year. Still, a high prevalence of GCA on current treatment was observed. More cases are diagnosed during spring and summer than in the winter.

@article{haugen_development_2022,
	title = {Development of radiographic classification criteria for hand osteoarthritis: a methodological report ({Phase} 2)},
	volume = {8},
	issn = {2056-5933},
	shorttitle = {Development of radiographic classification criteria for hand osteoarthritis},
	url = {https://doi.org/10.1136/rmdopen-2021-002024},
	doi = {10.1136/rmdopen-2021-002024},
	abstract = {OBJECTIVES: In Phase 1 of developing new hand osteoarthritis (OA) classification criteria, features associated with hand OA were identified in a population with hand complaints. Radiographic findings could better discriminate patients with hand OA and controls than clinical examination findings. The objective of Phase 2 was to achieve consensus on the features and their weights to be included in three radiographic criteria sets of overall hand OA, interphalangeal OA and thumb base OA.
METHODS: Multidisciplinary, international expert panels were convened. Patient vignettes were used to identify important features consistent with hand OA. A consensus-based decision analysis approach implemented using 1000minds software was applied to identify the most important features and their relative importance influencing the likelihood of symptoms being due to hand OA. Analyses were repeated for interphalangeal and thumb base OA. The reliability and validity of the proposed criteria sets were tested.
RESULTS: The experts agreed that the criteria sets should be applied in a population with pain, aching or stiffness in hand joint(s) not explained by another disease or acute injury. In this setting, five additional criteria were considered important: age, morning stiffness, radiographic osteophytes, radiographic joint space narrowing and concordance between symptoms and radiographic findings. The reliability and validity were very good.
CONCLUSION: Radiographic features were considered critical when determining whether a patient had symptoms due to hand OA. The consensus-based decision analysis approach in Phase 2 complemented the data-driven results from Phase 1, which will form the basis of the final classification criteria sets.},
	language = {eng},
	number = {1},
	journal = {RMD Open},
	author = {Haugen, Ida K. and Felson, David and Abhishek, Abhishek and Berenbaum, Francis and Edwards, John James and Herrero Beaumont, Gabriel and Hermann-Eriksen, Merete and Hill, Catherine L. and Ishimori, Mariko and Jonsson, Helgi and Karjalainen, Teemu and Leung, Ying Ying and Maheu, Emmanuel and Mallen, Christian D. and Moe, Rikke Helene and Ramonda, Roberta and Ritschl, Valentin and Stamm, Tanja A. and Szekanecz, Zoltan and van der Giesen, Florus J. and Ritt, Marco J. P. F. and Wittoek, Ruth and Kjeken, Ingvild and Osteras, Nina and van de Stadt, Lotte A. and Englund, Martin and Dziedzic, Krysia S. and Marshall, M. and Bierma-Zeinstra, Sita and Hansen, Paul and Greibrokk, Elsie and Smeets, Wilma and Kloppenburg, Margreet},
	month = feb,
	year = {2022},
	pmid = {35121640},
	pmcid = {PMC8819785},
	note = {Number: 1},
	keywords = {Hand, Humans, Osteoarthritis, Radiography, Reproducibility of Results, epidemiology, health care, osteoarthritis, outcome assessment},
	pages = {e002024},
}

OBJECTIVES: In Phase 1 of developing new hand osteoarthritis (OA) classification criteria, features associated with hand OA were identified in a population with hand complaints. Radiographic findings could better discriminate patients with hand OA and controls than clinical examination findings. The objective of Phase 2 was to achieve consensus on the features and their weights to be included in three radiographic criteria sets of overall hand OA, interphalangeal OA and thumb base OA. METHODS: Multidisciplinary, international expert panels were convened. Patient vignettes were used to identify important features consistent with hand OA. A consensus-based decision analysis approach implemented using 1000minds software was applied to identify the most important features and their relative importance influencing the likelihood of symptoms being due to hand OA. Analyses were repeated for interphalangeal and thumb base OA. The reliability and validity of the proposed criteria sets were tested. RESULTS: The experts agreed that the criteria sets should be applied in a population with pain, aching or stiffness in hand joint(s) not explained by another disease or acute injury. In this setting, five additional criteria were considered important: age, morning stiffness, radiographic osteophytes, radiographic joint space narrowing and concordance between symptoms and radiographic findings. The reliability and validity were very good. CONCLUSION: Radiographic features were considered critical when determining whether a patient had symptoms due to hand OA. The consensus-based decision analysis approach in Phase 2 complemented the data-driven results from Phase 1, which will form the basis of the final classification criteria sets.

@article{ali_proteomics_2022,
	title = {Proteomics profiling of human synovial fluid suggests increased protein interplay in early-osteoarthritis ({OA}) that is lost in late-stage {OA}},
	volume = {21},
	issn = {1535-9484},
	url = {https://doi.org/10.1016/j.mcpro.2022.100200},
	doi = {10.1016/j.mcpro.2022.100200},
	abstract = {The underlying molecular mechanisms in osteoarthritis (OA) development are largely unknown. This study explores the proteome and the pairwise interplay of proteins in synovial fluid from patients with late-stage knee OA (arthroplasty), early knee OA (arthroscopy due to degenerative meniscal tear), and from deceased controls without knee OA. Synovial fluid samples were analyzed using state-of-the-art mass spectrometry with data-independent acquisition. The differential expression of the proteins detected was clustered and evaluated with data mining strategies and a multilevel model. Group-specific slopes of associations were estimated between expressions of each pair of identified proteins to assess the co-expression (i.e., interplay) between the proteins in each group. More proteins were increased in early-OA versus controls than late-stage OA versus controls. For most of these proteins, the fold changes between late-stage OA versus controls and early-stage OA versus controls were remarkably similar suggesting potential involvement in the OA process. Further, for the first time, this study illustrated distinct patterns in protein co-expression suggesting that the interplay between the protein machinery is increased in early-OA and lost in late-stage OA. Further efforts should focus on earlier stages of the disease than previously considered.},
	language = {eng},
	number = {3},
	journal = {Molecular \& cellular proteomics: MCP},
	author = {Ali, Neserin and Turkiewicz, Aleksandra and Hughes, Velocity and Folkesson, Elin and Tjörnstand, Jon and Neuman, Paul and Önnerfjord, Patrik and Englund, Martin},
	month = mar,
	year = {2022},
	pmid = {35074580},
	pmcid = {PMC8941261},
	note = {Number: 3},
	keywords = {DIA, Humans, Mass Spectrometry, Osteoarthritis, Knee, Proteome, Proteomics, Synovial Fluid, early- and late-stage OA, osteoarthritis, proteomics, synovial fluid},
	pages = {100200},
}

The underlying molecular mechanisms in osteoarthritis (OA) development are largely unknown. This study explores the proteome and the pairwise interplay of proteins in synovial fluid from patients with late-stage knee OA (arthroplasty), early knee OA (arthroscopy due to degenerative meniscal tear), and from deceased controls without knee OA. Synovial fluid samples were analyzed using state-of-the-art mass spectrometry with data-independent acquisition. The differential expression of the proteins detected was clustered and evaluated with data mining strategies and a multilevel model. Group-specific slopes of associations were estimated between expressions of each pair of identified proteins to assess the co-expression (i.e., interplay) between the proteins in each group. More proteins were increased in early-OA versus controls than late-stage OA versus controls. For most of these proteins, the fold changes between late-stage OA versus controls and early-stage OA versus controls were remarkably similar suggesting potential involvement in the OA process. Further, for the first time, this study illustrated distinct patterns in protein co-expression suggesting that the interplay between the protein machinery is increased in early-OA and lost in late-stage OA. Further efforts should focus on earlier stages of the disease than previously considered.

@article{swain_clustering_2022,
	title = {Clustering of comorbidities and associated outcomes in people with osteoarthritis - {A} {UK} {Clinical} {Practice} {Research} {Datalink} study},
	volume = {30},
	issn = {1063-4584},
	url = {https://www.sciencedirect.com/science/article/pii/S1063458422000139},
	doi = {10.1016/j.joca.2021.12.013},
	abstract = {Objective
To examine the clusters of chronic conditions present in people with osteoarthritis and the associated risk factors and health outcomes.
Methods
Clinical Practice Research Datalink (CPRD) GOLD was used to identify people diagnosed with incident osteoarthritis (n = 221,807) between 1997 and 2017 and age (±2 years), gender, and practice matched controls (no osteoarthritis, n = 221,807) from UK primary care. Clustering of people was examined for 49 conditions using latent class analysis. The associations between cluster membership and covariates were quantified by odds ratios (OR) using multinomial logistic regression. General practice (GP) consultations, hospitalisations, and all-cause mortality rates were compared across the clusters identified at the time of first diagnosis of osteoarthritis (index date).
Results
In both groups, conditions largely grouped around five clusters: relatively healthy; cardiovascular (CV), musculoskeletal-mental health (MSK-MH), CV-musculoskeletal (CV-MSK) and metabolic (MB). In the osteoarthritis group, compared to the relatively healthy cluster, strong associations were seen for 1) age with all clusters; 2) women with the MB cluster (OR 5.55: 5.14–5.99); 3) obesity with the CV-MSK (OR 2.11: 2.03–2.20) and CV clusters (OR 2.03: 1.97–2.09). The CV-MSK cluster in the osteoarthritis group had the highest number of GP consultations and hospitalisations, and the mortality risk was 2.45 (2.33–2.58) times higher compared to the relatively healthy cluster.
Conclusions
Of the five identified clusters, CV-MSK, CV, and MSK-MH are more common in OA and CV-MSK cluster had higher health utilisation. Further research is warranted to better understand the mechanistic pathways and clinical implications.},
	number = {5},
	urldate = {2023-09-12},
	journal = {Osteoarthritis and Cartilage},
	author = {Swain, S. and Coupland, C. and Strauss, V. and Mallen, C. and Kuo, C. F. and Sarmanova, A. and Bierma-Zeinstra, S. M. A. and Englund, M. and Prieto-Alhambra, D. and Doherty, M. and Zhang, W.},
	month = may,
	year = {2022},
	keywords = {Clusters, Comorbidity, Health utilisation, Osteoarthritis, Primary care, UK},
	pages = {702--713},
}

Objective To examine the clusters of chronic conditions present in people with osteoarthritis and the associated risk factors and health outcomes. Methods Clinical Practice Research Datalink (CPRD) GOLD was used to identify people diagnosed with incident osteoarthritis (n = 221,807) between 1997 and 2017 and age (±2 years), gender, and practice matched controls (no osteoarthritis, n = 221,807) from UK primary care. Clustering of people was examined for 49 conditions using latent class analysis. The associations between cluster membership and covariates were quantified by odds ratios (OR) using multinomial logistic regression. General practice (GP) consultations, hospitalisations, and all-cause mortality rates were compared across the clusters identified at the time of first diagnosis of osteoarthritis (index date). Results In both groups, conditions largely grouped around five clusters: relatively healthy; cardiovascular (CV), musculoskeletal-mental health (MSK-MH), CV-musculoskeletal (CV-MSK) and metabolic (MB). In the osteoarthritis group, compared to the relatively healthy cluster, strong associations were seen for 1) age with all clusters; 2) women with the MB cluster (OR 5.55: 5.14–5.99); 3) obesity with the CV-MSK (OR 2.11: 2.03–2.20) and CV clusters (OR 2.03: 1.97–2.09). The CV-MSK cluster in the osteoarthritis group had the highest number of GP consultations and hospitalisations, and the mortality risk was 2.45 (2.33–2.58) times higher compared to the relatively healthy cluster. Conclusions Of the five identified clusters, CV-MSK, CV, and MSK-MH are more common in OA and CV-MSK cluster had higher health utilisation. Further research is warranted to better understand the mechanistic pathways and clinical implications.

@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},
	pmid = {35621350},
	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{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{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},
	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},
	pmid = {35307536},
	note = {Publisher: Elsevier},
	keywords = {Electronic health care record, Opioid, Total knee replacement},
	pages = {815--822},
}

@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{kiadaliri_gout_2022,
	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},
	author = {Kiadaliri, Ali and Neogi, Tuhina and Englund, Martin},
	month = jul,
	year = {2022},
	pmid = {35428711},
	note = {Publisher: The Journal of Rheumatology
Section: Gout},
	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{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{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{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},
	pmid = {35843480},
	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{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},
	pmid = {35988705},
	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{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{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.

@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{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},
	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
Publisher: Nature Publishing Group},
	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{ebrahimi_associations_2022,
	title = {Associations of human femoral condyle cartilage structure and composition with viscoelastic and constituent-specific material properties at different stages of osteoarthritis},
	volume = {145},
	issn = {0021-9290},
	url = {https://www.sciencedirect.com/science/article/pii/S0021929022004316},
	doi = {10.1016/j.jbiomech.2022.111390},
	abstract = {The relationships between structure and function in human knee femoral cartilage are not well-known at different stages of osteoarthritis. Thus, our aim was to characterize the depth-dependent composition and structure (proteoglycan content, collagen network organization and collagen content) of normal and osteoarthritic human femoral condyle cartilage (n = 47) and relate them to their viscoelastic and constituent-specific mechanical properties that are obtained through dynamic sinusoidal testing and fibril-reinforced poroelastic material modeling of stress-relaxation testing, respectively. We characterized the proteoglycan content using digital densitometry, collagen network organization (orientation angle and anisotropy) using polarized light microscopy and collagen content using Fourier transform infrared spectroscopy. In the superficial cartilage (0–10 \% of thickness), the collagen network disorganization and proteoglycan loss were associated with the smaller initial fibril network modulus - a parameter representing the pretension of the collagen network. Furthermore, the proteoglycan loss was associated with the greater strain-dependent fibril network modulus - a measure of nonlinear mechanical behavior. The proteoglycan loss was also associated with greater cartilage viscosity at a low loading frequency (0.005 Hz), while the collagen network disorganization was associated with greater cartilage viscosity at a high loading frequency (1 Hz). Our results suggest that proteoglycan loss and collagen network disorganization reduce the pretension of the collagen network while proteoglycan degradation also increases the nonlinear mechanical behavior of the collagen network. Further, the results also highlight that proteoglycan loss and collagen disorganization increase the viscosity of femoral cartilage, but their contribution to increased viscosity occurs in completely different loading frequencies.},
	language = {en},
	urldate = {2022-12-01},
	journal = {Journal of Biomechanics},
	author = {Ebrahimi, Mohammadhossein and Turkiewicz, Aleksandra and Finnilä, Mikko A. J. and Saarakkala, Simo and Englund, Martin and Korhonen, Rami K. and Tanska, Petri},
	month = dec,
	year = {2022},
	keywords = {Biomechanics, Collagen fibril network, Fibril-reinforced poroelastic, Finite element modeling, Proteoglycan},
	pages = {111390},
}

The relationships between structure and function in human knee femoral cartilage are not well-known at different stages of osteoarthritis. Thus, our aim was to characterize the depth-dependent composition and structure (proteoglycan content, collagen network organization and collagen content) of normal and osteoarthritic human femoral condyle cartilage (n = 47) and relate them to their viscoelastic and constituent-specific mechanical properties that are obtained through dynamic sinusoidal testing and fibril-reinforced poroelastic material modeling of stress-relaxation testing, respectively. We characterized the proteoglycan content using digital densitometry, collagen network organization (orientation angle and anisotropy) using polarized light microscopy and collagen content using Fourier transform infrared spectroscopy. In the superficial cartilage (0–10 % of thickness), the collagen network disorganization and proteoglycan loss were associated with the smaller initial fibril network modulus - a parameter representing the pretension of the collagen network. Furthermore, the proteoglycan loss was associated with the greater strain-dependent fibril network modulus - a measure of nonlinear mechanical behavior. The proteoglycan loss was also associated with greater cartilage viscosity at a low loading frequency (0.005 Hz), while the collagen network disorganization was associated with greater cartilage viscosity at a high loading frequency (1 Hz). Our results suggest that proteoglycan loss and collagen network disorganization reduce the pretension of the collagen network while proteoglycan degradation also increases the nonlinear mechanical behavior of the collagen network. Further, the results also highlight that proteoglycan loss and collagen disorganization increase the viscosity of femoral cartilage, but their contribution to increased viscosity occurs in completely different loading frequencies.

@article{rathmann_infection_2022,
	title = {Infection is associated with increased risk of {MPO}- but not {PR3}-{ANCA}-associated vasculitis},
	volume = {61},
	issn = {1462-0324},
	url = {https://doi.org/10.1093/rheumatology/keac163},
	doi = {10.1093/rheumatology/keac163},
	abstract = {To determine whether development of ANCA-associated vasculitis (AAV) shows a relationship with a prior infection and if prior infection affects disease characteristics and outcome.All incident cases of AAV diagnosed in a defined region of Sweden from 2000 through 2016 were identified. For each case, 10 individuals from the general population, matched for age, sex and area of residence, were selected. Infections occurring in AAV patients and controls prior to the date of AAV diagnosis (index date for respective controls) were identified using an administrative database. Conditional logistic regression models were used to calculate odds ratios (OR) of developing AAV. Occurrence, clinical characteristics and outcome of AAV were analysed with respect to prior infection.Two-hundred and seventy patients with AAV (48\% female) and 2687 controls were included. Prior to diagnosis/index date, 146 (54\%) AAV patients had been diagnosed with infection vs 1282 (48\%) controls, with OR for AAV 1.57 (95\% CI 1.18, 2.19) in those with infections of the upper respiratory tract and 1.68 (1.02, 2.77) in those with pneumonia. Difference from controls was significant in patients with MPO-ANCA 1.99 (95\% CI 1.25, 3.1) but not in those with PR3-ANCA 1.0 (0.61, 1.52). Patients with prior infection showed higher disease activity at AAV diagnosis. No differences in disease characteristics, comorbidities or outcome in those with and without prior infections were observed.Respiratory tract infections are positively associated with development of MPO- but not PR3-ANCA vasculitis. Prior infection is associated with higher disease activity at AAV diagnosis.},
	number = {12},
	urldate = {2023-09-12},
	journal = {Rheumatology},
	author = {Rathmann, Jens and Stamatis, Pavlos and Jönsson, Göran and Englund, Martin and Segelmark, Mårten and Jayne, David and Mohammad, Aladdin J},
	month = dec,
	year = {2022},
	pages = {4817--4826},
}

To determine whether development of ANCA-associated vasculitis (AAV) shows a relationship with a prior infection and if prior infection affects disease characteristics and outcome.All incident cases of AAV diagnosed in a defined region of Sweden from 2000 through 2016 were identified. For each case, 10 individuals from the general population, matched for age, sex and area of residence, were selected. Infections occurring in AAV patients and controls prior to the date of AAV diagnosis (index date for respective controls) were identified using an administrative database. Conditional logistic regression models were used to calculate odds ratios (OR) of developing AAV. Occurrence, clinical characteristics and outcome of AAV were analysed with respect to prior infection.Two-hundred and seventy patients with AAV (48% female) and 2687 controls were included. Prior to diagnosis/index date, 146 (54%) AAV patients had been diagnosed with infection vs 1282 (48%) controls, with OR for AAV 1.57 (95% CI 1.18, 2.19) in those with infections of the upper respiratory tract and 1.68 (1.02, 2.77) in those with pneumonia. Difference from controls was significant in patients with MPO-ANCA 1.99 (95% CI 1.25, 3.1) but not in those with PR3-ANCA 1.0 (0.61, 1.52). Patients with prior infection showed higher disease activity at AAV diagnosis. No differences in disease characteristics, comorbidities or outcome in those with and without prior infections were observed.Respiratory tract infections are positively associated with development of MPO- but not PR3-ANCA vasculitis. Prior infection is associated with higher disease activity at AAV diagnosis.

@article{tiulpin_predicting_2022,
	title = {Predicting total knee arthroplasty from ultrasonography using machine learning},
	volume = {4},
	issn = {2665-9131},
	url = {https://www.sciencedirect.com/science/article/pii/S2665913122000875},
	doi = {10.1016/j.ocarto.2022.100319},
	abstract = {Objective
To investigate the value of ultrasonographic data in predicting total knee replacement (TKR).
Design
Data from the Musculoskeletal Pain in Ullensaker study (MUST) was linked to the Norwegian Arthroplasty Register to form a 5–7 year prospective cohort study of 630 persons (69\% women, mean (SD) age 64 (8.7) years). We examined the predictive power of ultrasound (US) features, i.e. osteophytes, meniscal extrusion, synovitis in the suprapatellar recess, femoral cartilage thickness, and quality for future knee osteoarthritis (OA) surgery. We investigated 4 main settings for multivariate predictive modeling: 1) clinical predictors (age, sex, body mass index, knee injury, familial OA and workload), 2) radiographic data (assessed by the Kellgren Lawrence grade, KL) with clinical predictors, 3) US features and clinical predictors. Finally, we also considered an ensemble of models 2) and 3) and used it as our fifth model. All models were compared using the Average Precision (AP) and the Area Under Receiver Operating Characteristic Curve (AUC) metrics.
Results
Clinical predictors yielded AP of 0.11 (95\% confidence interval [CI] 0.05–0.23) and AUC of 0.69 (0.58–0.79). Clinical predictors with KL grade yielded AP of 0.20 (0.12–0.33) and AUC of 0.81 (0.67–0.90). The clinical variables with ultrasound yielded AP of 0.17 (0.08–0.30) and AUC of 0.79 (0.69–0.86).
Conclusion
Ultrasonographic examination of the knee may provide added value to basic clinical and demographic descriptors when predicting TKR. While it does not achieve the same predictive performance as radiography, it can provide additional value to the radiographic examination.},
	language = {en},
	number = {4},
	urldate = {2023-02-02},
	journal = {Osteoarthritis and Cartilage Open},
	author = {Tiulpin, Aleksei and Saarakkala, Simo and Mathiessen, Alexander and Hammer, Hilde Berner and Furnes, Ove and Nordsletten, Lars and Englund, Martin and Magnusson, Karin},
	month = dec,
	year = {2022},
	note = {Number: 4},
	keywords = {Machine learning, Multivariate predictive modeling, Total knee replacement, Ultrasonography},
	pages = {100319},
}

Objective To investigate the value of ultrasonographic data in predicting total knee replacement (TKR). Design Data from the Musculoskeletal Pain in Ullensaker study (MUST) was linked to the Norwegian Arthroplasty Register to form a 5–7 year prospective cohort study of 630 persons (69% women, mean (SD) age 64 (8.7) years). We examined the predictive power of ultrasound (US) features, i.e. osteophytes, meniscal extrusion, synovitis in the suprapatellar recess, femoral cartilage thickness, and quality for future knee osteoarthritis (OA) surgery. We investigated 4 main settings for multivariate predictive modeling: 1) clinical predictors (age, sex, body mass index, knee injury, familial OA and workload), 2) radiographic data (assessed by the Kellgren Lawrence grade, KL) with clinical predictors, 3) US features and clinical predictors. Finally, we also considered an ensemble of models 2) and 3) and used it as our fifth model. All models were compared using the Average Precision (AP) and the Area Under Receiver Operating Characteristic Curve (AUC) metrics. Results Clinical predictors yielded AP of 0.11 (95% confidence interval [CI] 0.05–0.23) and AUC of 0.69 (0.58–0.79). Clinical predictors with KL grade yielded AP of 0.20 (0.12–0.33) and AUC of 0.81 (0.67–0.90). The clinical variables with ultrasound yielded AP of 0.17 (0.08–0.30) and AUC of 0.79 (0.69–0.86). Conclusion Ultrasonographic examination of the knee may provide added value to basic clinical and demographic descriptors when predicting TKR. While it does not achieve the same predictive performance as radiography, it can provide additional value to the radiographic examination.

@article{kamps_occurrence_2022,
	title = {Occurrence of comorbidity following osteoarthritis diagnosis: a cohort study in the {Netherlands}},
	issn = {1063-4584},
	shorttitle = {Occurrence of comorbidity following osteoarthritis diagnosis},
	url = {https://www.sciencedirect.com/science/article/pii/S1063458422009578},
	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 = {en},
	urldate = {2023-02-02},
	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 = dec,
	year = {2022},
	keywords = {Comorbidity, Electronic health record (EHR), Osteoarthritis, Primary care},
}

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{filbay_evidence_2022,
	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},
	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},
	pmid = {36328403},
	note = {Number: 2
Publisher: BMJ Publishing Group Ltd and British Association of Sport and Exercise Medicine
Section: Original research},
	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{hellberg_3d_2022,
	title = {{3D} analysis and grading of calcifications from ex {VIVO} human meniscus},
	volume = {31},
	issn = {1063-4584},
	url = {https://www.sciencedirect.com/science/article/pii/S1063458422008962},
	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 = {en},
	number = {4},
	urldate = {2022-11-22},
	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 = nov,
	year = {2022},
	keywords = {Calcification grading, Meniscal calcification, Micro-computed tomography, Volumetric analysis},
	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{kiadaliri_variability_2021,
	title = {Variability in end-of-life healthcare use in patients with osteoarthritis: a population-based matched cohort study},
	volume = {29},
	issn = {1063-4584},
	shorttitle = {Variability in end-of-life healthcare use in patients with osteoarthritis},
	url = {https://www.sciencedirect.com/science/article/pii/S1063458421008360},
	doi = {10.1016/j.joca.2021.07.001},
	abstract = {Purpose
To investigate the patterns of healthcare use (HCU) at the last year of life in persons with osteoarthritis (OA).
Methods
Using linked registers, we identified persons aged≥ 65 years who died during 2003–2014 and were resided in the Skåne region during 5-year prior to death. Among these, we randomly matched decedents with a principal OA diagnosis prior to the last year of life (OA cohort, n = 17,993) with up to 4 comparators without OA by sex, age at death, and year of death (n = 59,945). We measured monthly HCU for each decedent during last year of life and applied two-part regression models to estimate HCU attributable to OA. Group-based trajectory modelling (GBTM) was used to detect distinct trajectories of HCU within the OA cohort.
Results
During last 12-month of life, each person with OA had, on average, 2.5 (95\% CI 2.2, 2.7) excess healthcare consultations and 1.8 (95\% CI 1.3, 2.2) more inpatient days than those without OA. While both cohorts observed increasing trends in HCU towards death, excess healthcare consultations attributable to OA declined and inpatient days increased as death approached. For both healthcare consultations and inpatient days, GBTM identified four distinct trajectory classes. While underlying cause of death and age were the most important predictors of class membership, the overall predictive accuracy was poor.
Conclusion
OA was associated with excess HCU especially hospital-based care during the last year of life. However, there seem to be distinct trajectory classes within the OA patient population.},
	number = {10},
	urldate = {2023-09-12},
	journal = {Osteoarthritis and Cartilage},
	author = {Kiadaliri, A. and Englund, M.},
	month = oct,
	year = {2021},
	keywords = {End of life, Healthcare consultation, Osteoarthritis, Sweden, Trajectory},
	pages = {1418--1425},
}

Purpose To investigate the patterns of healthcare use (HCU) at the last year of life in persons with osteoarthritis (OA). Methods Using linked registers, we identified persons aged≥ 65 years who died during 2003–2014 and were resided in the Skåne region during 5-year prior to death. Among these, we randomly matched decedents with a principal OA diagnosis prior to the last year of life (OA cohort, n = 17,993) with up to 4 comparators without OA by sex, age at death, and year of death (n = 59,945). We measured monthly HCU for each decedent during last year of life and applied two-part regression models to estimate HCU attributable to OA. Group-based trajectory modelling (GBTM) was used to detect distinct trajectories of HCU within the OA cohort. Results During last 12-month of life, each person with OA had, on average, 2.5 (95% CI 2.2, 2.7) excess healthcare consultations and 1.8 (95% CI 1.3, 2.2) more inpatient days than those without OA. While both cohorts observed increasing trends in HCU towards death, excess healthcare consultations attributable to OA declined and inpatient days increased as death approached. For both healthcare consultations and inpatient days, GBTM identified four distinct trajectory classes. While underlying cause of death and age were the most important predictors of class membership, the overall predictive accuracy was poor. Conclusion OA was associated with excess HCU especially hospital-based care during the last year of life. However, there seem to be distinct trajectory classes within the OA patient population.

@article{xie_association_2021,
	title = {Association of tramadol vs codeine prescription dispensation with mortality and other adverse clinical outcomes},
	volume = {326},
	issn = {0098-7484},
	url = {https://doi.org/10.1001/jama.2021.15255},
	doi = {10.1001/jama.2021.15255},
	abstract = {Although tramadol is increasingly used to manage chronic noncancer pain, few safety studies have compared it with other opioids.To assess the associations of tramadol, compared with codeine, with mortality and other adverse clinical outcomes as used in outpatient settings.Retrospective, population-based, propensity score–matched cohort study using a primary care database with routinely collected medical records and pharmacy dispensations covering more than 80\% of the population of Catalonia, Spain (≈6 million people). Patients 18 years or older with 1 or more year of available data and dispensation of tramadol or codeine (2007-2017) were included and followed up to December 31, 2017.New prescription dispensation of tramadol or codeine (no dispensation in the previous year).Outcomes studied were all-cause mortality, cardiovascular events, fractures, constipation, delirium, falls, opioid abuse/dependence, and sleep disorders within 1 year after the first dispensation. Absolute rate differences (ARDs) and hazard ratios (HRs) with 95\% confidence intervals were calculated using cause-specific Cox models.Of the 1 093 064 patients with a tramadol or codeine dispensation during the study period (326 921 for tramadol, 762 492 for codeine, 3651 for both drugs concomitantly), a total of 368 960 patients (184 480 propensity score–matched pairs) were included after study exclusions and propensity score matching (mean age, 53.1 [SD, 16.1] years; 57.3\% women). Compared with codeine, tramadol dispensation was significantly associated with a higher risk of all-cause mortality (incidence, 13.00 vs 5.61 per 1000 person-years; HR, 2.31 [95\% CI, 2.08-2.56]; ARD, 7.37 [95\% CI, 6.09-8.78] per 1000 person-years), cardiovascular events (incidence, 10.03 vs 8.67 per 1000 person-years; HR, 1.15 [95\% CI, 1.05-1.27]; ARD, 1.36 [95\% CI, 0.45-2.36] per 1000 person-years), and fractures (incidence, 12.26 vs 8.13 per 1000 person-years; HR, 1.50 [95\% CI, 1.37-1.65]; ARD, 4.10 [95\% CI, 3.02-5.29] per 1000 person-years). No significant difference was observed for the risk of falls, delirium, constipation, opioid abuse/dependence, or sleep disorders.In this population-based cohort study, a new prescription dispensation of tramadol, compared with codeine, was significantly associated with a higher risk of subsequent all-cause mortality, cardiovascular events, and fractures, but there was no significant difference in the risk of constipation, delirium, falls, opioid abuse/dependence, or sleep disorders. The findings should be interpreted cautiously, given the potential for residual confounding.},
	number = {15},
	urldate = {2021-10-27},
	journal = {JAMA},
	author = {Xie, Junqing and Strauss, Victoria Y. and Martinez-Laguna, Daniel and Carbonell-Abella, Cristina and Diez-Perez, Adolfo and Nogues, Xavier 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 = oct,
	year = {2021},
	note = {Number: 15},
	pages = {1504--1515},
}

Although tramadol is increasingly used to manage chronic noncancer pain, few safety studies have compared it with other opioids.To assess the associations of tramadol, compared with codeine, with mortality and other adverse clinical outcomes as used in outpatient settings.Retrospective, population-based, propensity score–matched cohort study using a primary care database with routinely collected medical records and pharmacy dispensations covering more than 80% of the population of Catalonia, Spain (≈6 million people). Patients 18 years or older with 1 or more year of available data and dispensation of tramadol or codeine (2007-2017) were included and followed up to December 31, 2017.New prescription dispensation of tramadol or codeine (no dispensation in the previous year).Outcomes studied were all-cause mortality, cardiovascular events, fractures, constipation, delirium, falls, opioid abuse/dependence, and sleep disorders within 1 year after the first dispensation. Absolute rate differences (ARDs) and hazard ratios (HRs) with 95% confidence intervals were calculated using cause-specific Cox models.Of the 1 093 064 patients with a tramadol or codeine dispensation during the study period (326 921 for tramadol, 762 492 for codeine, 3651 for both drugs concomitantly), a total of 368 960 patients (184 480 propensity score–matched pairs) were included after study exclusions and propensity score matching (mean age, 53.1 [SD, 16.1] years; 57.3% women). Compared with codeine, tramadol dispensation was significantly associated with a higher risk of all-cause mortality (incidence, 13.00 vs 5.61 per 1000 person-years; HR, 2.31 [95% CI, 2.08-2.56]; ARD, 7.37 [95% CI, 6.09-8.78] per 1000 person-years), cardiovascular events (incidence, 10.03 vs 8.67 per 1000 person-years; HR, 1.15 [95% CI, 1.05-1.27]; ARD, 1.36 [95% CI, 0.45-2.36] per 1000 person-years), and fractures (incidence, 12.26 vs 8.13 per 1000 person-years; HR, 1.50 [95% CI, 1.37-1.65]; ARD, 4.10 [95% CI, 3.02-5.29] per 1000 person-years). No significant difference was observed for the risk of falls, delirium, constipation, opioid abuse/dependence, or sleep disorders.In this population-based cohort study, a new prescription dispensation of tramadol, compared with codeine, was significantly associated with a higher risk of subsequent all-cause mortality, cardiovascular events, and fractures, but there was no significant difference in the risk of constipation, delirium, falls, opioid abuse/dependence, or sleep disorders. The findings should be interpreted cautiously, given the potential for residual confounding.

@article{mollestam_association_2021,
	title = {Association of clinically relevant carpal tunnel syndrome with type of work and level of education: a general-population study},
	volume = {11},
	copyright = {2021 The Author(s)},
	issn = {2045-2322},
	shorttitle = {Association of clinically relevant carpal tunnel syndrome with type of work and level of education},
	url = {https://www.nature.com/articles/s41598-021-99242-8},
	doi = {10.1038/s41598-021-99242-8},
	abstract = {Carpal tunnel syndrome (CTS) is a common cause of work disability. The association with occupational load and education level has not been established in general-population studies. The purpose of this study was to investigate the association of clinically relevant CTS with work and education. From the Healthcare Register of Skane region (population 1.2 million) in southern Sweden we identified all individuals, aged 17–57 years, with first-time physician-made CTS diagnosis during 2004–2008. For each case we randomly sampled 4 referents, without a CTS diagnosis, from the general population matched by sex, age, and residence. We retrieved data about work and education from the national database. The study comprised 5456 individuals (73\% women) with CTS and 21,667 referents. We found a significant association between physician-diagnosed CTS and type of work and level of education in both women and men. Compared with white-collar workers, the odds ratio (OR) for CTS among blue-collar workers was 1.67 (95\% CI 1.54–1.81) and compared with light work, OR in light-moderate work was 1.37 (1.26–1.50), moderate work 1.70 (1.51–1.91), and heavy manual labor 1.96 (1.75–2.20). Compared with low-level education, OR for CTS in intermediate level was 0.82 (0.76–0.89) and high-level 0.48 (0.44–0.53). In women and men there is significant association with a dose–response pattern between clinically relevant CTS and increasing manual work load and lower education level. These findings could be important in design and implementation of preventive measures.},
	language = {en},
	number = {1},
	urldate = {2021-10-12},
	journal = {Scientific Reports},
	author = {Möllestam, Kamelia and Englund, Martin and Atroshi, Isam},
	month = oct,
	year = {2021},
	note = {Bandiera\_abtest: a
Cc\_license\_type: cc\_by
Cg\_type: Nature Research Journals
Number: 1
Primary\_atype: Research
Publisher: Nature Publishing Group
Subject\_term: Diseases;Medical research;Risk factors
Subject\_term\_id: diseases;medical-research;risk-factors},
	pages = {19850},
}

Carpal tunnel syndrome (CTS) is a common cause of work disability. The association with occupational load and education level has not been established in general-population studies. The purpose of this study was to investigate the association of clinically relevant CTS with work and education. From the Healthcare Register of Skane region (population 1.2 million) in southern Sweden we identified all individuals, aged 17–57 years, with first-time physician-made CTS diagnosis during 2004–2008. For each case we randomly sampled 4 referents, without a CTS diagnosis, from the general population matched by sex, age, and residence. We retrieved data about work and education from the national database. The study comprised 5456 individuals (73% women) with CTS and 21,667 referents. We found a significant association between physician-diagnosed CTS and type of work and level of education in both women and men. Compared with white-collar workers, the odds ratio (OR) for CTS among blue-collar workers was 1.67 (95% CI 1.54–1.81) and compared with light work, OR in light-moderate work was 1.37 (1.26–1.50), moderate work 1.70 (1.51–1.91), and heavy manual labor 1.96 (1.75–2.20). Compared with low-level education, OR for CTS in intermediate level was 0.82 (0.76–0.89) and high-level 0.48 (0.44–0.53). In women and men there is significant association with a dose–response pattern between clinically relevant CTS and increasing manual work load and lower education level. These findings could be important in design and implementation of preventive measures.

@article{magnusson_relationship_2021,
	title = {Relationship between magnetic resonance imaging features and knee pain over six years in knees without radiographic osteoarthritis at baseline},
	volume = {73},
	issn = {2151-464X, 2151-4658},
	url = {https://onlinelibrary.wiley.com/doi/10.1002/acr.24394},
	doi = {10.1002/acr.24394},
	abstract = {Objective. To explore whether magnetic resonance imaging (MRI) features suggestive of knee osteoarthritis (OA) are associated with presence of knee pain in possible early-­stage OA development.
Methods. We included 294 participants from the Osteoarthritis Initiative (mean ± SD age 50 ± 3 years; 50\% women) with baseline Kellgren/Lawrence grade of 0 in both knees, all of whom had received knee MRIs at 4 different time points over 6 years (baseline, 24, 48, and 72 months). Using a linear mixed model (knees matched within individuals), we studied whether MRI features (meniscal body extrusion [in mm], cartilage area loss [score 0–3­ 9], cartilage full thickness loss [range 0–­16], osteophytes [range 0–­29], meniscal integrity [range 0–­10], bone marrow lesions [BMLs] including bone marrow cysts [range 0–­20], Hoffa-­or effusion-s­ ynovitis [absent/present], and popliteal cysts [absent/present]) were associated with knee-s­ pecific pain as reported on the Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire using a 0–­100 scale (worst to best).
Results. The differences in KOOS knee pain score for a knee with a 1 unit higher score on MRI were the following: meniscal extrusion –­1.52 (95\% confidence interval [95\% CI] –2­ .35, –­0.69); cartilage area loss –0­ .23 (95\% CI –0­ .48, 0.02); cartilage full thickness loss –­1.04 (95\% CI –­1.58, –­0.50); osteophytes –­0.32 (95\% CI –­0.61, –­0.03); meniscal integrity –0­ .28 (95\% CI –­0.58, 0.02); BMLs including potential cysts –­0.19 (95\% CI –­0.55, 0.16); synovitis 0.23 (95\% CI –­1.14, 1.60); and popliteal cysts 0.86 (95\% CI –0­ .56, 2.29).
Conclusion. Meniscal extrusion, full thickness cartilage loss, and osteophytes are associated with having more knee pain. Although these features may be relevant targets for future trials, the clinical relevance of our findings is unclear because no feature was associated with a clinically important difference in knee pain.},
	language = {en},
	number = {11},
	urldate = {2021-11-08},
	journal = {Arthritis Care \& Research},
	author = {Magnusson, Karin and Turkiewicz, Aleksandra and Kumm, Jaanika and Zhang, Fan and Englund, Martin},
	month = nov,
	year = {2021},
	note = {Number: 11},
	pages = {1659--1666},
}

Objective. To explore whether magnetic resonance imaging (MRI) features suggestive of knee osteoarthritis (OA) are associated with presence of knee pain in possible early-­stage OA development. Methods. We included 294 participants from the Osteoarthritis Initiative (mean ± SD age 50 ± 3 years; 50% women) with baseline Kellgren/Lawrence grade of 0 in both knees, all of whom had received knee MRIs at 4 different time points over 6 years (baseline, 24, 48, and 72 months). Using a linear mixed model (knees matched within individuals), we studied whether MRI features (meniscal body extrusion [in mm], cartilage area loss [score 0–3­ 9], cartilage full thickness loss [range 0–­16], osteophytes [range 0–­29], meniscal integrity [range 0–­10], bone marrow lesions [BMLs] including bone marrow cysts [range 0–­20], Hoffa-­or effusion-s­ ynovitis [absent/present], and popliteal cysts [absent/present]) were associated with knee-s­ pecific pain as reported on the Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire using a 0–­100 scale (worst to best). Results. The differences in KOOS knee pain score for a knee with a 1 unit higher score on MRI were the following: meniscal extrusion –­1.52 (95% confidence interval [95% CI] –2­ .35, –­0.69); cartilage area loss –0­ .23 (95% CI –0­ .48, 0.02); cartilage full thickness loss –­1.04 (95% CI –­1.58, –­0.50); osteophytes –­0.32 (95% CI –­0.61, –­0.03); meniscal integrity –0­ .28 (95% CI –­0.58, 0.02); BMLs including potential cysts –­0.19 (95% CI –­0.55, 0.16); synovitis 0.23 (95% CI –­1.14, 1.60); and popliteal cysts 0.86 (95% CI –0­ .56, 2.29). Conclusion. Meniscal extrusion, full thickness cartilage loss, and osteophytes are associated with having more knee pain. Although these features may be relevant targets for future trials, the clinical relevance of our findings is unclear because no feature was associated with a clinically important difference in knee pain.

@article{ryden_proteomill_2021,
	title = {{ProteoMill}: efficient network-based functional analysis portal for proteomics data},
	volume = {37},
	issn = {1367-4803},
	shorttitle = {{ProteoMill}},
	url = {https://doi.org/10.1093/bioinformatics/btab373},
	doi = {10.1093/bioinformatics/btab373},
	abstract = {Functional analysis has become a common approach to incorporate biological knowledge into the analysis of omics data, and to explore molecular events that govern a disease state. It is though only one step in a wider analytical pipeline that typically requires use of multiple individual analysis software. There is currently a need for a well-integrated omics analysis tool that performs all the steps. The ProteoMill portal is developed as an R Shiny application and integrates all necessary steps from data-upload, converting identifiers, to quality control, differential expression and network-based functional analysis into a single fast, interactive easy to use workflow. Further, it maintains annotation data sources up to date, overcoming a common problem with use of outdated information and seamlessly integrates multiple R-packages for an improved user-experience. The functionality provided in this software can benefit researchers by facilitating the exploratory analysis of proteomics data.ProteoMill is available at https://proteomill.com.},
	number = {20},
	urldate = {2023-09-12},
	journal = {Bioinformatics},
	author = {Rydén, Martin and Englund, Martin and Ali, Neserin},
	month = oct,
	year = {2021},
	pages = {3491--3493},
}

Functional analysis has become a common approach to incorporate biological knowledge into the analysis of omics data, and to explore molecular events that govern a disease state. It is though only one step in a wider analytical pipeline that typically requires use of multiple individual analysis software. There is currently a need for a well-integrated omics analysis tool that performs all the steps. The ProteoMill portal is developed as an R Shiny application and integrates all necessary steps from data-upload, converting identifiers, to quality control, differential expression and network-based functional analysis into a single fast, interactive easy to use workflow. Further, it maintains annotation data sources up to date, overcoming a common problem with use of outdated information and seamlessly integrates multiple R-packages for an improved user-experience. The functionality provided in this software can benefit researchers by facilitating the exploratory analysis of proteomics data.ProteoMill is available at https://proteomill.com.