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1.	Watt, F. E., et al. (författare) Towards prevention of post-traumatic osteoarthritis : report from an international expert working group on considerations for the design and conduct of interventional studies following acute knee injury 2019 Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 27:1, s. 23-33 Tidskriftsartikel (refereegranskat)abstract Objective: There are few guidelines for clinical trials of interventions for prevention of post-traumatic osteoarthritis (PTOA), reflecting challenges in this area. An international multi-disciplinary expert group including patients was convened to generate points to consider for the design and conduct of interventional studies following acute knee injury. Design: An evidence review on acute knee injury interventional studies to prevent PTOA was presented to the group, alongside overviews of challenges in this area, including potential targets, biomarkers and imaging. Working groups considered pre-identified key areas: eligibility criteria and outcomes, biomarkers, injury definition and intervention timing including multi-modality interventions. Consensus agreement within the group on points to consider was generated and is reported here after iterative review by all contributors. Results: The evidence review identified 37 studies. Study duration and outcomes varied widely and 70% examined surgical interventions. Considerations were grouped into three areas: justification of inclusion criteria including the classification of injury and participant age (as people over 35 may have pre-existing OA); careful consideration in the selection and timing of outcomes or biomarkers; definition of the intervention(s)/comparator(s) and the appropriate time-window for intervention (considerations may be particular to intervention type). Areas for further research included demonstrating the utility of patient-reported outcomes, biomarkers and imaging outcomes from ancillary/cohort studies in this area, and development of surrogate clinical trial endpoints that shorten the duration of clinical trials and are acceptable to regulatory agencies. Conclusions: These considerations represent the first international consensus on the conduct of interventional studies following acute knee joint trauma.
2.	Agel, J., et al. (författare) The burden of musculoskeletal conditions at the start of the new millennium 2003 Ingår i: World Health Organization - Technical Report Series. - 0512-3054. ; :919, s. 218-218 Tidskriftsartikel (refereegranskat)
3.	Styrkarsdottir, Unnur, et al. (författare) Whole-genome sequencing identifies rare genotypes in COMP and CHADL associated with high risk of hip osteoarthritis 2017 Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 49:5, s. 801-805 Tidskriftsartikel (refereegranskat)abstract We performed a genome-wide association study of total hip replacements, based on variants identified through whole-genome sequencing, which included 4,657 Icelandic patients and 207,514 population controls. We discovered two rare signals that strongly associate with osteoarthritis total hip replacement: a missense variant, c.1141G>C (p.Asp369His), in the COMP gene (allelic frequency = 0.026%, P = 4.0 × 10-12, odds ratio (OR) = 16.7) and a frameshift mutation, rs532464664 (p.Val330Glyfs∗106), in the CHADL gene that associates through a recessive mode of inheritance (homozygote frequency = 0.15%, P = 4.5 × 10-18, OR = 7.71). On average, c.1141G>C heterozygotes and individuals homozygous for rs532464664 had their hip replacement operation 13.5 years and 4.9 years earlier than others (P = 0.0020 and P = 0.0026), respectively. We show that the full-length CHADL transcript is expressed in cartilage. Furthermore, the premature stop codon introduced by the CHADL frameshift mutation results in nonsense-mediated decay of the mutant transcripts.
4.	Semb, G, et al. (författare) Erratum 2017 Ingår i: Journal of plastic surgery and hand surgery. - 2000-6764. ; 51:2, s. 158-158 Tidskriftsartikel (refereegranskat)
5.	Chockalingam, P. S., et al. (författare) Elevated aggrecanase activity in a rat model of joint injury is attenuated by an aggrecanase specific inhibitor 2011 Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 19:3, s. 315-323 Tidskriftsartikel (refereegranskat)abstract Objective: To evaluate aggrecanase activity after traumatic knee injury in a rat model by measuring the level of aggrecanase-generated Ala-Arg-Gly-aggrecan (ARG-aggrecan) fragments in synovial fluid, and compare with ARG-aggrecan release into joint fluid following human knee injury. To evaluate the effect of small molecule inhibitors on induced aggrecanase activity in the rat model. Method: An enzyme-linked immunosorbent assay (ELISA) was developed to measure ARG-aggrecan levels in animal and human joint fluids. A rat model of meniscal tear (MT)-induced joint instability was used to assess ARG-aggrecan release into joint fluid and the effects of aggrecanase inhibition. Synovial fluids were also obtained from patients with acute joint injury or osteoarthritis and assayed for ARG-aggrecan. Results: Joint fluids from human patients after knee injury showed significantly enhanced levels of ARG-aggrecan compared to uninjured reference subjects. Similarly, synovial fluid ARG-aggrecan levels increased following surgically-induced joint instability in the rat MT model, which was significantly attenuated by orally dosing the animals with AGG-523, an aggrecanase specific inhibitor. Conclusions: Aggrecanase-generated aggrecan fragments were rapidly released into human and rat joint fluids after injury to the knee and remained elevated over a prolonged period. Our findings in human and preclinical models strengthen the connection between aggrecanase activity in joints and knee injury and disease. The ability of a small molecule aggrecanase inhibitor to reduce the release of aggrecanase-generated aggrecan fragments into rat joints suggests that pharmacologic inhibition of aggrecanase activity in humans may be an effective treatment for slowing cartilage degradation following joint injury. (C) 2010 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
6.	Chockalingam, P. S., et al. (författare) Tenascin-C levels in synovial fluid are elevated after injury to the human and canine joint and correlate with markers of inflammation and matrix degradation 2013 Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 21:2, s. 339-345 Tidskriftsartikel (refereegranskat)abstract Objective: We have previously shown the capacity of tenascin-C (TN-C) to induce inflammatory mediators and matrix degradation in vitro in human articular cartilage. The objective of the present study was to follow TN-C release into knee synovial fluid after acute joint injury or in joint disease, and to correlate TN-C levels with markers of cartilage matrix degradation and inflammation. Method: Human knee synovial fluid samples (n = 164) were from a cross-sectional convenience cohort. Diagnostic groups were knee healthy reference, knee anterior cruciate ligament rupture, with or without concomitant meniscus lesions, isolated knee meniscus injury, acute inflammatory arthritis (AIA) and knee osteoarthritis (OA). TN-C was measured in synovial fluid samples using an enzyme-linked immunosorbent assay (ELISA) and results correlated to other cartilage markers. TN-C release was also monitored in joints of dogs that underwent knee instability surgery. Results: Statistically significantly higher levels of TN-C compared to reference subjects were observed in the joint fluid of all human disease groups and in the dogs that underwent knee instability surgery. Statistically significant correlations were observed between the TN-C levels in the synovial fluid of the human patients and the levels of aggrecanase-dependent Ala-Arg-Gly-aggrecan (ARG-aggrecan) fragments and matrix metalloproteinases 1 and 3. Conclusions: We find highly elevated levels of TN-C in human knee joints after injury, AIA or OA that correlated with markers of cartilage degradation and inflammation. TN-C in synovial fluid may serve dual roles as a marker of joint damage and a stimulant of further joint degradation. (C) 2012 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
7.	Kerkhof, H. J. M., et al. (författare) Recommendations for standardization and phenotype definitions in genetic studies of osteoarthritis: the TREAT-OA consortium 2011 Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 19:3, s. 254-264 Tidskriftsartikel (refereegranskat)abstract Objective: To address the need for standardization of osteoarthritis (OA) phenotypes by examining the effect of heterogeneity among symptomatic (SOA) and radiographic osteoarthritis (ROA) phenotypes. Methods: Descriptions of OA phenotypes of the 28 studies involved in the TREAT-OA consortium were collected. We investigated whether different OA definitions result in different association results by creating various hip OA definitions in one large population based cohort (the Rotterdam Study I (RSI)) and testing those for association with gender, age and body mass index using one-way ANOVA. For ROA, we standardized the hip-, knee- and hand ROA definitions and calculated prevalence's of ROA before and after standardization in nine cohort studies. This procedure could only be performed in cohort studies and standardization of SOA definitions was not feasible at this moment. Results: In this consortium, all studies with SOA phenotypes (knee, hip and hand) used a different definition and/or assessment of OA status. For knee-, hip- and hand ROA five, four and seven different definitions were used, respectively. Different hip ROA definitions do lead to different association results. For example, we showed in the RSI that hip OA defined as "at least definite joint space narrowing (JSN) and one definite osteophyte" was not associated with gender (P=0.22), but defined as "at least one definite osteophyte" was significantly associated with gender (P=3 x 10(-9)). Therefore, a standardization process was undertaken for ROA definitions. Before standardization a wide range of ROA prevalence's was observed in the nine cohorts studied. After standardization the range in prevalence of knee- and hip ROA was small. Conclusion: Phenotype definitions influence the prevalence of OA and association with clinical variables. ROA phenotypes within the TREAT-OA consortium were standardized to reduce heterogeneity and improve power in future genetics studies. (C) 2010 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
8.	Leyland, K. M., et al. (författare) Harmonising measures of knee and hip osteoarthritis in population-based cohort studies : an international study 2018 Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 26:7, s. 872-879 Tidskriftsartikel (refereegranskat)abstract Objective: Population-based osteoarthritis (OA) cohorts provide vital data on risk factors and outcomes of OA, however the methods to define OA vary between cohorts. We aimed to provide recommendations for combining knee and hip OA data in extant and future population cohort studies, in order to facilitate informative individual participant level analyses. Method: International OA experts met to make recommendations on: 1) defining OA by X-ray and/or pain; 2) compare The National Health and Nutrition Examination Survey (NHANES)-type OA pain questions; 3) the comparability of the Western Ontario & McMaster Universities Osteoarthritis Index (WOMAC) scale to NHANES-type OA pain questions; 4) the best radiographic scoring method; 5) the usefulness of other OA outcome measures. Key issues were explored using new analyses in two population-based OA cohorts (Multicenter Osteoarthritis Study; MOST and Osteoarthritis Initiative OAI). Results: OA should be defined by both symptoms and radiographs, with symptoms alone as a secondary definition. Kellgren and Lawrence (K/L) grade ≥2 should be used to define radiographic OA (ROA). The variable wording of pain questions can result in varying prevalence between 41.0% and 75.4%, however questions where the time anchor is similar have high sensitivity and specificity (91.2% and 89.9% respectively). A threshold of 3 on a 0–20 scale (95% CI 2.1, 3.9) in the WOMAC pain subscale demonstrated equivalence with the preferred NHANES-type question. Conclusion: This research provides recommendations, based on expert agreement, for harmonising and combining OA data in existing and future population-based cohorts.
9.	Meneses, S. R F, et al. (författare) Clinical algorithms to aid osteoarthritis guideline dissemination 2016 Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 24:9, s. 1487-1499 Forskningsöversikt (refereegranskat)abstract Background: Numerous scientific organisations have developed evidence-based recommendations aiming to optimise the management of osteoarthritis (OA). Uptake, however, has been suboptimal. The purpose of this exercise was to harmonize the recent recommendations and develop a user-friendly treatment algorithm to facilitate translation of evidence into practice. Methods: We updated a previous systematic review on clinical practice guidelines (CPGs) for OA management. The guidelines were assessed using the Appraisal of Guidelines for Research and Evaluation for quality and the standards for developing trustworthy CPGs as established by the National Academy of Medicine (NAM). Four case scenarios and algorithms were developed by consensus of a multidisciplinary panel. Results: Sixteen guidelines were included in the systematic review. Most recommendations were directed toward physicians and allied health professionals, and most had multi-disciplinary input. Analysis for trustworthiness suggests that many guidelines still present a lack of transparency. A treatment algorithm was developed for each case scenario advised by recommendations from guidelines and based on panel consensus. Conclusion: Strategies to facilitate the implementation of guidelines in clinical practice are necessary. The algorithms proposed are examples of how to apply recommendations in the clinical context, helping the clinician to visualise the patient flow and timing of different treatment modalities.
10.	Styrkarsdottir, Unnur, et al. (författare) GWAS of bone size yields twelve loci that also affect height, BMD, osteoarthritis or fractures 2019 Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1 Tidskriftsartikel (refereegranskat)abstract Bone area is one measure of bone size that is easily derived from dual-energy X-ray absorptiometry (DXA) scans. In a GWA study of DXA bone area of the hip and lumbar spine (N ≥ 28,954), we find thirteen independent association signals at twelve loci that replicate in samples of European and East Asian descent (N = 13,608 – 21,277). Eight DXA area loci associate with osteoarthritis, including rs143384 in GDF5 and a missense variant in COL11A1 (rs3753841). The strongest DXA area association is with rs11614913[T] in the microRNA MIR196A2 gene that associates with lumbar spine area (P = 2.3 × 10 −42 , β = −0.090) and confers risk of hip fracture (P = 1.0 × 10 −8 , OR = 1.11). We demonstrate that the risk allele is less efficient in repressing miR-196a-5p target genes. We also show that the DXA area measure contributes to the risk of hip fracture independent of bone density.
11.	Willadsen, E., et al. (författare) Scandcleft randomized trials of primary surgery for unilateral cleft lip and palate: Speech proficiency at 10 years of age 2023 Ingår i: International journal of language and communication disorders. - : WILEY. - 1368-2822 .- 1460-6984. ; 58:3, s. 892-909 Tidskriftsartikel (refereegranskat)abstract Background & AimTo assess consonant proficiency and velopharyngeal function in 10-year-old children born with unilateral cleft lip and palate (UCLP) within the Scandcleft project. Methods & ProceduresThree parallel group, randomized, clinical trials were undertaken as an international multicentre study by nine cleft teams in five countries. Three different surgical protocols for primary palate repair (Arm B-Lip and soft palate closure at 3-4 months, hard palate closure at 36 months, Arm C-Lip closure at 3-4 months, hard and soft palate closure at 12 months, and Arm D-Lip closure at 3-4 months combined with a single-layer closure of the hard palate using a vomer flap, soft palate closure at 12 months) were tested against a common procedure (Arm A-Lip and soft palate closure at 3-4 months followed by hard palate closure at 12 months) in the total cohort of 431 children born with a non-syndromic UCLP. Speech audio and video recordings of 399 children were available and perceptually analysed. Percentage of consonants correct (PCC) from a naming test, an overall rating of velopharyngeal competence (VPC) (VPC-Rate), and a composite measure (VPC-Sum) were reported. Outcomes & ResultsThe mean levels of consonant proficiency (PCC score) in the trial arms were 86-92% and between 58% and 83% of the children had VPC (VPC-Sum). Only 50-73% of the participants had a consonant proficiency level with their peers. Girls performed better throughout. Long delay of the hard palate repair (Arm B) indicated lower PCC and simultaneous hard and soft palate closure higher (Arm C). However, the proportion of participants with primary VPC (not including velopharyngeal surgeries) was highest in Arm B (68%) and lowest in Arm C (47%). Conclusions & ImplicationsThe speech outcome in terms of PCC and VPC was low across the trials. The different protocols had their pros and cons and there is no obvious evidence to recommend any of the protocols as superior. Aspects other than primary surgical method, such as time after velopharyngeal surgery, surgical experience, hearing level, language difficulties and speech therapy, need to be thoroughly reviewed for a better understanding of what has affected speech outcome at 10 years. WHAT THIS PAPER ADDSWhat is already known on the subjectSpeech outcomes at 10 years of age in children treated for UCLP are sparse and contradictory. Previous studies have examined speech outcomes and the relationship with surgical intervention in 5-year-olds. What this study adds to the existing knowledgeSpeech outcomes based on standardized assessment in a large group of 10-year-old children born with UCLP and surgically treated according to different protocols are presented. While speech therapy had been provided, a large proportion of the children across treatment protocols still needed further speech therapy. What are the potential or actual clinical implications of this work?Aspects other than surgery and speech function might add to the understanding of what affects speech outcome. Effective speech therapy should be available for children in addition to primary surgical repair of the cleft and secondary surgeries if needed.
12.	Zhang, W., et al. (författare) OARSI recommendations for the management of hip and knee osteoarthritis. Part III : Changes in evidence following systematic cumulative update of research published through January 2009. 2010 Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 18:4, s. 476-499 Tidskriftsartikel (refereegranskat)abstract Objective: To update evidence for available therapies in the treatment of hip and knee osteoarthritis (OA) and to examine whether research evidence has changed from 31 January 2006 to 31 January 2009. Methods: A systematic literature search was undertaken using MEDLINE, EMBASE, CINAHL, AMED, Science Citation Index and the Cochrane Library. The quality of studies was assessed. Effect sizes (ESs) and numbers needed to treat were calculated for efficacy. Relative risks, hazard ratios (HRs) or odds ratios were estimated for side effects. Publication bias and heterogeneity were examined. Sensitivity analysis was undertaken to compare the evidence pooled in different years and different qualities. Cumulative meta-analysis was used to examine the stability of evidence. Results: Sixty-four systematic reviews, 266 randomised controlled trials (RCTs) and 21 new economic evaluations (EEs) were published between 2006 and 2009. Of 51 treatment modalities, new data on efficacy have been published for more than half (26/39, 67%) of those for which research evidence was available in 2006. Among non-pharmacological therapies, ES for pain relief was unchanged for self-management, education, exercise and acupuncture. However, with new evidence the ES for pain relief for weight reduction reached statistical significance, increasing from 0.13 [95% confidence interval (CI) -0.12, 0.36] in 2006 to 0.20 (95% CI 0.00, 0.39) in 2009. By contrast, the ES for electromagnetic therapy which was large in 2006 (ES=0.77, 95% CI 0.36, 1.17) was no longer significant (ES=0.16, 95% CI -0.08, 0.39). Among pharmacological therapies, the cumulative evidence for the benefits and harms of oral and topical non-steroidal anti-inflammatory drugs, diacerhein and intra-articular (IA) corticosteroid was not greatly changed. The ES for pain relief with acetaminophen diminished numerically, but not significantly, from 0.21 (0.02, 0.41) to 0.14 (0.05, 0.22) and was no longer significant when analysis was restricted to high quality trials (ES=0.10, 95% CI -0.0, 0.23). New evidence for increased risks of hospitalisation due to perforation, peptic ulceration and bleeding with acetaminophen >3. g/day have been published (HR=1.20, 95% CI 1.03, 1.40). ES for pain relief from IA hyaluronic acid, glucosamine sulphate, chondroitin sulphate and avocado soybean unsponifiables also diminished and there was greater heterogeneity of outcomes and more evidence of publication bias. Among surgical treatments further negative RCTs of lavage/debridement were published and the pooled results demonstrated that benefits from this modality of therapy were no greater than those obtained from placebo. Conclusion: Publication of a large amount of new research evidence has resulted in changes in the calculated risk-benefit ratio for some treatments for OA. Regular updating of research evidence can help to guide best clinical practice.
13.	Ahlin, Sofie, 1985, et al. (författare) Fracture risk after three bariatric surgery procedures in Swedish obese subjects : up to 26 years follow-up of a controlled intervention study 2020 Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 287:5, s. 546-557 Tidskriftsartikel (refereegranskat)abstract Background: Previous studies have reported an increased fracture risk after bariatric surgery. Objective: To investigate the association between different bariatric surgery procedures and fracture risk. Methods: Incidence rates and hazard ratios for fracture events were analysed in the Swedish Obese Subjects study; an ongoing, nonrandomized, prospective, controlled intervention study. Hazard ratios were adjusted for risk factors for osteoporosis and year of inclusion. Information on fracture events were captured from the Swedish National Patient Register. The current analysis includes 2007 patients treated with bariatric surgery (13.3% gastric bypass, 18.7% gastric banding, and 68.0% vertical banded gastroplasty) and 2040 control patients with obesity matched on group level based on 18 variables. Median follow-up was between 15.1 and 17.9 years for the different treatment groups. Results: During follow-up, the highest incidence rate for first-time fracture was observed in the gastric bypass group (22.9 per 1000 person-years). The corresponding incidence rates were 10.4, 10.7 and 9.3 per 1000 person-years for the vertical banded gastroplasty, gastric banding and control groups, respectively. The risk of fracture was increased in the gastric bypass group compared with the control group (adjusted hazard ratio [adjHR] 2.58; 95% confidence interval [CI] 2.02–3.31; P < 0.001), the gastric banding group (adjHR 1.99; 95%CI 1.41–2.82; P < 0.001), and the vertical banded gastroplasty group (adjHR 2.15; 95% CI 1.66–2.79; P < 0.001). Conclusions: The risk of fracture is increased after gastric bypass surgery. Our findings highlight the need for long-term follow-up of bone health for patients undergoing this treatment.
14.	Altman, R., et al. (författare) Design and conduct of clinical trials in patients with osteoarthritis : Recommendations from a task force of the Osteoarthritic Research Society 1996 Ingår i: Osteoarthritis and Cartilage. - 1063-4584. ; 4:4, s. 217-243 Tidskriftsartikel (refereegranskat)
15.	Bannuru, R. R., et al. (författare) OARSI guidelines for the non-surgical management of knee, hip, and polyarticular osteoarthritis 2019 Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. Tidskriftsartikel (refereegranskat)abstract Objective: To update and expand upon prior Osteoarthritis Research Society International (OARSI) guidelines by developing patient-focused treatment recommendations for individuals with Knee, Hip, and Polyarticular osteoarthritis (OA) that are derived from expert consensus and based on objective review of high-quality meta-analytic data. Methods: We sought evidence for 60 unique interventions. A systematic search of all relevant databases was conducted from inception through July 2018. After abstract and full-text screening by two independent reviewers, eligible studies were matched to PICO questions. Data were extracted and meta-analyses were conducted using RevMan software. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Evidence Profiles were compiled using the GRADEpro web application. Voting for Core Treatments took place first. Four subsequent voting sessions took place via anonymous online survey, during which Panel members were tasked with voting to produce recommendations for all joint locations and comorbidity classes. We designated non-Core treatments to Level 1A, 1B, 2, 3, 4A, 4B, or 5, based on the percentage of votes in favor, in addition to the strength of the recommendation. Results: Core Treatments for Knee OA included arthritis education and structured land-based exercise programs with or without dietary weight management. Core Treatments for Hip and Polyarticular OA included arthritis education and structured land-based exercise programs. Topical non-steroidal anti-inflammatory drugs (NSAIDs) were strongly recommended for individuals with Knee OA (Level 1A). For individuals with gastrointestinal comorbidities, COX-2 inhibitors were Level 1B and NSAIDs with proton pump inhibitors Level 2. For individuals with cardiovascular comorbidities or frailty, use of any oral NSAID was not recommended. Intra-articular (IA) corticosteroids, IA hyaluronic acid, and aquatic exercise were Level 1B/Level 2 treatments for Knee OA, dependent upon comorbidity status, but were not recommended for individuals with Hip or Polyarticular OA. The use of Acetaminophen/Paracetamol (APAP) was conditionally not recommended (Level 4A and 4B), and the use of oral and transdermal opioids was strongly not recommended (Level 5). A treatment algorithm was constructed in order to guide clinical decision-making for a variety of patient profiles, using recommended treatments as input for each decision node. Conclusion: These guidelines offer comprehensive and patient-centered treatment profiles for individuals with Knee, Hip, and Polyarticular OA. The treatment algorithm will facilitate individualized treatment decisions regarding the management of OA.
16.	Eyles, J.P., et al. (författare) Clinical Outcomes Of Osteoarthritis Management Programs: A Project Of The Oa Trial Bank And Oarsi Joint Effort Initiative Using Individual Participant Data 2023 Ingår i: Osteoarthritis and Cartilage. - : Elsevier. - 1063-4584 .- 1522-9653. ; 31, s. S385-S386 Tidskriftsartikel (refereegranskat)abstract Purpose: People living with osteoarthritis (OA) often do not receive best evidence care. Coordinated OA management programs (OAMPs) have been implemented to address this global evidence-practice gap. An OAMP is defined as a package of care with the following: i) a personalized management plan; ii) with reassessment and progression; iii) using a minimum of 2 core treatments (education, exercise, weight control), and; iv) optional adjunctive therapies. Existing OAMP models differ in treatment mode, intensity, duration, the health professionals delivering care, and the healthcare systems and settings they operate within. Randomized trials (RCTs) and cohort studies assess the outcomes of different OAMPs, however, these models are unlikely to ever be compared in RCTs due to the huge expense and complicated logistics required. Prognosis research provides another method of comparing outcomes of different OAMP models. This study aimed to estimate the pain and self-reported function outcomes (at 12-, 26- and 52-weeks) of people with hip and/or knee OA who participated in international OAMPs. It also aimed to describe the characteristics of OAMP participants.Methods: This study was undertaken by members of the OARSI Joint Effort Initiative (JEI), in collaboration with the OA Trial Bank (Erasmus MC, Netherlands). RCTs and clinical cohorts assessing OAMPs were identified through the JEI membership and literature searches. Eligible studies included data from an ongoing OAMP, in any real-world setting, with participants who were diagnosed with hip or knee OA, and longitudinal measures of patient-reported pain and function. The investigators of eligible studies were invited to complete data delivery agreements with the OA Trial Bank, share individual participant data (IPD), contribute to study design and authorship. Investigators ensured they had local ethics review board approval to contribute IPD to the OA Trial bank. Each dataset was converted to a common format to enable merging into one dataset. The IPD were evaluated to convert pain and function variables to standardized scales as appropriate. Pain scores were converted to a 0-100 point scale (100 worst). Function scores were converted to a 0-100 point scale (100 best). A generalized estimating equations (GEE) model analysis was performed to assess the change in pain and function from baseline across weeks 12, 26, and 52. The model specification was based on an unstructured correlation structure and robust standard errors. Pain and function estimates were adjusted by age, sex and body mass index (BMI). Data analyses were carried out using Stata 15 (StataCorp 2015) and SPSS 17.Results: The investigators of 13 international OAMPs were invited to take part. IPD from 9 OAMPs were delivered: the OA Chronic Care Program, Ramsay Health OA Management Program, Joint Health Program, University of Wisconsin Health Knee and Hip Comprehensive Non-Surgical OA Management Clinic, Improved Management of Patients With Hip and Knee OA in Primary Health Care, Joint Academy, Amsterdam OA cohort, Management of OA In Consultations, and Collaborative model of care between Orthopaedics and allied healthcare professionals in knee OA. The characteristics of the OAMPs are summarised in table 1. The OAMPs were conducted in-person except for the Joint Academy that was implemented as an online OAMP. Individual participant data from 9819 participants were analyzed. The cohort studies were missing large amounts of data, as expected in clinical practice. The characteristics of OAMP participants are summarised in Table 2. The majority of OAMP participants reported the knee as their index joint, their mean age ranged between 62- 67 years, 58-74% were female, 25-48% were working and mean BMI indicated they were overweight at baseline. Pain was most commonly assessed using a Numeric Rating Scale or validated questionnaires e.g. the Knee Injury and OA Outcome Scale (KOOS). Function was mostly assessed using validated questionnaires such as the KOOS. The pain and fuction measured in the original datasets are reported in Table 1. The changes in pain and function of the OAMP participants from baseline across weeks 12, 26, and 52 are summarised in Table 3. There were reductions in pain scores and improvements in function scores seen across all programs at the majority of timepoints.Conclusions: We established the first data bank of IPD from different international OAMPs. Analysis of the IPD demonstrated modest improvements in pain and function across the programs at all timepoints. The most rapid improvements were made by week-12, however, these gains were maintained at week-52. In future work this project will use IPD meta-analysis to identify prognostic factors of people with OA who participate in OAMPs.
17.	Filbay, S. R., et al. (författare) Thirty years of publishing osteoarthritis research in perspective — a special journal issue to mark the 30th anniversary of Osteoarthritis and Cartilage 2023 Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 31:6, s. 721-722 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
18.	Kraus, V. B., et al. (författare) Application of biomarkers in the development of drugs intended for the treatment of osteoarthritis 2011 Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 19:5, s. 515-542 Tidskriftsartikel (refereegranskat)abstract Objective: Osteoarthritis (OA) is a chronic and slowly progressive disease for which biomarkers may be able to provide a more rapid indication of therapeutic responses to therapy than is currently available; this could accelerate and facilitate OA drug discovery and development programs. The goal of this document is to provide a summary and guide to the application of in vitro (biochemical and other soluble) biomarkers in the development of drugs for OA and to outline and stimulate a research agenda that will further this goal. Methods: The Biomarkers Working Group representing experts in the field of OA biomarker research from both academia and industry developed this consensus document between 2007 and 2009 at the behest of the Osteoarthritis Research Society International Federal Drug Administration initiative (OARSI FDA initiative). Results: This document summarizes definitions and classification systems for biomarkers, the current outcome measures used in OA clinical trials, applications and potential utility of biomarkers for development of OA therapeutics, the current state of qualification of OA-related biomarkers, pathways for biomarker qualification, critical needs to advance the use of biomarkers for drug development, recommendations regarding practices and clinical trials, and a research agenda to advance the science of OA-related biomarkers. Conclusions: Although many OA-related biomarkers are currently available they exist in various states of qualification and validation. The biomarkers that are likely to have the earliest beneficial impact on clinical trials fall into two general categories, those that will allow targeting of subjects most likely to either respond and/or progress (prognostic value) within a reasonable and manageable time frame for a clinical study (for instance within 1-2 years for an OA trial), and those that provide early feedback for preclinical decision-making and for trial organizers that a drug is having the desired biochemical effect. As in vitro biomarkers are increasingly investigated in the context of specific drug treatments, advances in the field can be expected that will lead to rapid expansion of the list of available biomarkers with increasing understanding of the molecular processes that they represent. (C) 2011 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
19.	Larsson, S., et al. (författare) Surgical reconstruction of ruptured anterior cruciate ligament prolongs trauma-induced increase of inflammatory cytokines in synovial fluid : An exploratory analysis in the KANON trial 2017 Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 25:9, s. 1443-1451 Tidskriftsartikel (refereegranskat)abstract Objective: Prospectively monitor how treatment of acutely ruptured anterior cruciate ligament (ACL) affects biomarkers of inflammation and proteolytic degradation over 5 years. Design: We studied 119 subjects with acute ACL injury from the randomized controlled knee anterior cruciate ligament, non-surgical versus surgical treatment (KANON)-trial (Clinical trial ISRCTN 84752559) who had synovial fluid, serum and urine samples available from at least two out of six visits over 5 years after acute ACL rupture. All subjects followed a similar rehabilitation protocol where, according to randomization, 60 also had early ACL reconstruction and 59 had the option to undergo a delayed ACL reconstruction if needed. Interleukin (IL)-6, IL-8, IL-10, interferon-gamma (IFNγ), tumor necrosis factor (TNF), amino acids alanine, arginine, glycine, serine (ARGS)-aggrecan, C-terminal crosslinking telopeptide type II collagen (CTX-II) and N-terminal crosslinking telopeptide type I collagen (NTX-I) were quantified by enzyme-linked immunosorbent assays (ELISA). Results: Subjects randomized to early ACL reconstruction had higher cytokine concentrations in index knee synovial fluid at 4 months (IL-6, IL-8, IL-10, TNF), 8 months (IL-6 and TNF) and at 5 years (IFNγ) compared to those randomized to optional delayed reconstruction. Those that underwent delayed ACL reconstruction within 5 years (30 subjects), had higher synovial fluid concentrations of IL-6 at 5 years compared to those treated with rehabilitation alone. No differences between groups were noted for ARGS-aggrecan in synovial fluid and serum or CTX-II and NTX-I in urine over 5 years, neither as randomized nor as treated. Conclusions: Surgical ACL reconstruction constitutes a second trauma to the acutely injured joint resulting in a prolonged elevation of already high synovial fluid levels of inflammatory cytokines.
20.	Lohmander, L. S., et al. (författare) Bariatric surgery, osteoarthritis and arthroplasty of the hip and knee in Swedish Obese Subjects - up to 31 years follow-up of a controlled intervention study. 2023 Ingår i: Osteoarthritis and cartilage. - : Elsevier BV. - 1522-9653 .- 1063-4584. ; 31:5, s. 636-646 Tidskriftsartikel (refereegranskat)abstract To study the long-term effect of obesity and bariatric surgery on incidences of osteoarthritis and arthroplasty of hip and knee.Hazard ratios (HR) and incidence rates (IR) of osteoarthritis and arthroplasty of hip and knee were studied in the prospective, controlled, non-randomized Swedish Obese Subjects (SOS) study (bariatric surgery group, n=2007; matched controls given usual obesity care, n=2040) and the SOS reference cohort (n=1135, general population). Osteoarthritis diagnosis and arthroplasty for osteoarthritis were captured from the National Swedish Patient Register. Median follow-up time was 21.2 (IQR 16.4-24.8), 22.9 (IQR 19.1-25.7), and 20.1 years (IQR 18.7-20.9) for the control group, surgery group and reference cohort, respectively.The surgery group displayed lower incidence of hip osteoarthritis (IR 5.3, 95% CI 4.7-6.1) compared to controls (IR 6.6, 95% CI 5.9-7.5, adjHR 0.83, 95% CI 0.69-1.00) but similar incidence of hip arthroplasty. Similar incidence of knee osteoarthritis was observed in the surgery group and controls, but knee arthroplasty was more common in the surgery group (IR 7.4, 95% CI 6.6-8.2 and 5.6, 95% CI 4.9-6.4, adjHR 1.45, 95% CI 1.22-1.74). The reference cohort displayed lower incidences of osteoarthritis and arthroplasty of hip and knee compared with the surgery group and controls.Bariatric surgery did not normalize the increased risk of knee and hip osteoarthritis in patients with obesity but was associated with an increased incidence of knee arthroplasty compared to the control group. With the limitations inherent to the present data, additional studies are needed to confirm these results.clinicaltrials.gov Identifier: NCT01479452.
21.	Lohmander, L. S., et al. (författare) Stromelysin, tissue inhibitor of metalloproteinases and proteoglycan fragments in human knee joint fluid after injury 1993 Ingår i: Journal of Rheumatology. - 0315-162X. ; 20:8, s. 1362-1368 Tidskriftsartikel (refereegranskat)abstract Objective. To determine in a cross sectional study the concentrations of stromelysin, tissue inhibitor of metalloproteinases (TIMP), and proteoglycan fragments in knee synovial fluid (SF) at different times after injury to cruciate ligament or meniscus. Methods. Joint fluid samples were obtained from patients with knee injury diagnosed by arthroscopy. Concentrations of stromelysin-1 and TIMP-1 were determined by immunoassay with monoclonal and polyclonal antibodies. Cartilage proteoglycan fragments were quantified by immunoassay with polyclonal antibodies or by dye precipitation. Results. Average concentrations of stromelysin increased 40-fold in association with injury, and after about 6 months decreased to a plateau level about 10-fold increased compared to a reference group with healthy knees. TIMP and proteoglycan levels also increased in similar temporal patterns, but less markedly. Increased average SF levels of these markers were maintained for at least 17 years after injury. SF from knees with injury contained a 1.5 to 2.5 molar excess of stromelysin over TIMP, while reference joint fluids contained a 2-fold molar excess of TIMP over stromelysin. Conclusion. The persistent changes in SF markers after joint injury may be associated with the cartilage destruction and frequent development of posttraumatic osteoarthritis in this group of patients.
22.	Lohmander, S., et al. (författare) Structures of N- and O-linked oligosaccharides from chondrosarcoma proteoglycan 1981 Ingår i: Seminars in Arthritis and Rheumatism. - : Elsevier BV. - 0049-0172. ; 11:1 SUPPL. 1, s. 12-13 Tidskriftsartikel (refereegranskat)
23.	Luyten, F. P., et al. (författare) Toward classification criteria for early osteoarthritis of the knee 2018 Ingår i: Seminars in Arthritis and Rheumatism. - : Elsevier BV. - 0049-0172. ; 47:4, s. 457-463 Tidskriftsartikel (refereegranskat)abstract Objective: To propose draft classification criteria for early stage osteoarthritis (OA) of the knee for use in a primary care setting. Methods: A group of basic scientists, physician-scientists, rheumatologists, orthopedic surgeons, and physiotherapists in a workshop setting discussed potential classification criteria for early osteoarthritis of the knee. The workshop was divided into sessions around relevant topics with short state of the art presentations followed by breakout sessions, consensus discussions, and consolidation into a consensus document. Results: Three classes of criteria were agreed: (1) Pain, symptoms/signs, self-reported function, and quality of life using tools such as KOOS: scoring ≤85% in at least 2 out of these 4 categories; (2) Clinical examination: at least 1 present out of joint line tenderness or crepitus; (3) Knee radiographs: Kellgren & Lawrence (KL) grade of 0 or 1. MRI is at present not recommended as an aid to identify or define early OA in routine clinical practice or primary care, in light of the absence of validated consensus criteria and the high population prevalence of structural joint changes detected by this method. Biomarkers may have future utility in early OA classification, but no individual or set of biomarkers is yet robust enough. Conclusion: Based on our consensus proposal, draft classification criteria for early OA of the knee for use in clinical studies should include patient reported outcomes such as pain and function, together with clinical signs and KL grade 0-1 on radiographs.
24.	Mehta, S. P., et al. (författare) Cross-cultural validation of the ICOAP and physical function short forms of the HOOS and KOOS in a multi-country study of patients with hip and knee osteoarthritis 2016 Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 24:12, s. 2077-2081 Tidskriftsartikel (refereegranskat)abstract Objective To evaluate the internal consistency and construct validity of the Physical Function short-forms for the Hip and Knee Injury Osteoarthritis Outcome Scores (HOOS-PS/KOOS-PS) and the Intermittent and Constant Osteoarthritis Pain (ICOAP) in a nine country study of patients consulting for total hip or knee replacement (THR or TKR). Methods Patients completed HOOS-PS or KOOS-PS, ICOAP and Western Ontario and McMaster Universities' Osteoarthritis Index (WOMAC) pain and physical function subscales at their consultation visit. Internal consistency was calculated using Cronbach's alpha. The association of HOOS-PS/KOOS-PS and ICOAP with WOMAC pain and function subscales was calculated with Spearman correlation coefficients with 95% confidence intervals. Results HOOS-PS/KOOS-PS and ICOAP demonstrated high internal consistency across countries (alpha 0.75–0.96 (hip) and 0.76–0.95 (knee)). Both HOOS-PS and KOOS-PS demonstrated high correlations (0.76–0.90 and 0.75–0.91, respectively) with WOMAC function in all countries. ICOAP exhibited moderate to high correlations with WOMAC pain and function subscales (0.53–0.84 (hip) and 0.43–0.84 (knee)). Conclusion The psychometric properties of the HOOS-PS/KOOS-PS, and ICOAP were maintained across all countries.
25.	Moskalewski, S., et al. (författare) Influence of colchicine and vinblastine on the Golgi complex and matrix deposition in chondrocyte aggregates. An ultrastructural study 1975 Ingår i: Experimental Cell Research. - : Elsevier BV. - 0014-4827. ; 95:2, s. 440-454 Tidskriftsartikel (refereegranskat)abstract Fetal guinea-pig epiphyseal chondrocytes were isolated enzymatically, aggregated, and the aggregates maintained in organ culture. As revealed by light and electron microscopy, the cultures produced a typical cartilaginous matrix, but no calcification occurred. Exposure of aggregating cells, or preformed aggregates, to colchicine or vinblastihe at 10-5 M concentration led to disappearance of the microtubules, dissociation of the Golgi complex into single dictyosomes, and clustering of lysosomes. Thus, in treated cells the dictyosomes with accompanying vesicular structures were dispersed throughout the cytoplasm, whereas they were localized in a well-defined juxtanuclear region in control cells. The number and size of the cisternae forming a dictyosome were often reduced. Cells treated with vinblastine displayed macrotubules and an increased number of phagosomes. Both drugs reduced the deposition of intercellular matrix. In cells first exposed to either of the drugs for 2 or 5 days and then transferred to fresh medium for 3 or 6 days, the microtubules reappeared, the Golgi complex regained its normal appearance, and the amount of matrix increased. These findings are discussed in view of present concepts of the role of microtubules in cell secretion.
26.	Nilsson, Bo, et al. (författare) Structures of N-linked and O-linked oligosaccharides on proteoglycan monomer isolated from the Swarm rat chondrosarcoma 1982 Ingår i: Journal of Biological Chemistry. - 0021-9258. ; 257:18, s. 10920-10927 Tidskriftsartikel (refereegranskat)
27.	Odenbring, S., et al. (författare) Cartilage regeneration after proximal tibial osteotomy for medial gonarthrosis : An arthroscopic, roentgenographic, and histologic study 1992 Ingår i: Clinical Orthopaedics and Related Research. - 0009-921X. ; :277, s. 210-216 Tidskriftsartikel (refereegranskat)abstract High tibial osteotomy for medial gonarthrosis was performed in 28 patients (28 knees). At the time of surgery, arthroscopy was also performed and a cartilage-bone biopsy was obtained. Postoperatively, 15 patients were randomized to a cylinder plaster cast, whereas 13 patients had a hinged cast brace for early knee mobilization. At follow-up examination, two years after surgery, 16 patients accepted an arthroscopic examination with a cartilage- bone biopsy. In overcorrected knees, cartilage regeneration was found in eight of 14 patients on the medial tibial condyle and in nine of 14 on the medial femoral condyle. The main repair feature was proliferation of fibrocartilage, which covered bone and areas of fibrillated cartilage and filled vertical clefts in hyaline cartilage. The hyaline cartilage showed an increased cellularity with numerous nests of proliferating chondrocytes. No correlation was found between clinical outcome and the degree of cartilage regeneration as observed by arthroscopy, biopsy, or roentgenography. Knees with a brace postoperatively had better knee flexion two years after surgery. No difference in cartilage regeneration was recorded between knees with a plaster cast or a cast brace postoperatively.
28.	Struglics, A., et al. (författare) Molecular and imaging biomarkers of local inflammation at 2 years after anterior cruciate ligament injury do not associate with patient reported outcomes at 5 years 2020 Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 28:3, s. 356-362 Tidskriftsartikel (refereegranskat)abstract Objective: To estimate the association between molecular or imaging inflammatory biomarkers at 2 years after anterior cruciate ligament (ACL) injury and patient-reported outcomes at 5 years. Methods: For 116 ACL-injured patients, molecular biomarkers of inflammation (synovial fluid and serum cytokines) and Hoffa- and effusion-synovitis as visualized on magnetic resonance imaging (MRI) were assessed 2 years post-injury. Knee injury and Osteoarthritis Outcome Score (KOOS) and SF-36 were assessed at 2 and 5 years. We used multiple imputation to handle biomarker values that were below the level of detection or missing, and linear regression for statistical analyses. Results: None of the synovial fluid cytokines or imaging biomarkers of inflammation at 2 years were associated with any of the patient-reported outcomes at 5 years. With each log10 unit higher of serum tumor necrosis factor concentration the knee-related quality of life of KOOS was increased (i.e., better outcome) by 35 (95% confidence interval 7 to 63) points. No other serum biomarker measured at 2 years was associated with patient-reported outcome at 5 years. Conclusion: Local joint inflammation assessed by biomarkers in synovial fluid and Hoffa- and effusion-synovitis on MRI at 2 years after an ACL injury did not associate with patient-reported outcomes at 5 years. Thus, chronic inflammation in the ACL-injured knee, as reflected by the biomarkers studied here, seems not to be a key determinant for the long-term patient-reported outcomes.
29.	van Middelkoop, M, et al. (författare) The OA Trial Bank: meta-analysis of individual patient data from knee and hip osteoarthritis trials show that patients with severe pain exhibit greater benefit from intra-articular glucocorticoids. 2016 Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 24:7, s. 1143-1152 Tidskriftsartikel (refereegranskat)abstract To evaluate the efficacy of intra-articular (IA) glucocorticoids for knee or hip osteoarthritis (OA) in specific subgroups of patients with severe pain and inflammatory signs using individual patient data (IPD) from existing trials.
30.	Zhang, W., et al. (författare) EULAR evidence-based recommendations for the diagnosis of knee osteoarthritis 2010 Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 69:3, s. 483-489 Forskningsöversikt (refereegranskat)abstract Objective To develop evidence-based recommendations for the diagnosis of knee osteoarthritis (OA). Methods The multidisciplinary guideline development group, representing 12 European countries, generated 10 key propositions regarding diagnosis using a Delphi consensus approach. For each recommendation, research evidence was searched systematically. Whenever possible, the sensitivity, specificity and likelihood ratio were calculated for individual diagnostic indicators and a diagnostic ladder was developed using Bayes' method. Secondary analyses were undertaken to test directly the recommendations using multiple predictive models in two populations from the UK and the Netherlands. Strength of recommendation was assessed by the EULAR visual analogue scale. Results Recommendations covered the definition of knee OA and its risk factors, subsets, typical symptoms and signs, the use of imaging and laboratory tests and differential diagnosis. Three symptoms (persistent knee pain, limited morning stiffness and reduced function) and three signs (crepitus, restricted movement and bony enlargement) appeared to be the most useful. Assuming a 12.5% background prevalence of knee OA in adults aged >= 45 years, the estimated probability of having radiographic knee OA increased with increasing number of positive features, to 99% when all six symptoms and signs were present. The performance of the recommendations in the study populations varied according to the definition of knee OA, background risk and number of tests applied. Conclusion 10 key recommendations for diagnosis of knee OA were developed using both research evidence and expert consensus. Although there is no agreed reference standard, thorough clinical assessment alone can provide a confident rule-in diagnosis.
31.	Abbott, Allan, 1978-, et al. (författare) Understanding the role of diabetes in the osteoarthritis disease and treatment process: a study protocol for the Swedish Osteoarthritis and Diabetes (SOAD) cohort 2019 Ingår i: Bmj Open. - : BMJ. - 2044-6055. ; 9:12 Tidskriftsartikel (refereegranskat)abstract Introduction Osteoarthritis (OA) is the most common form of arthritis and a leading cause of disability worldwide. Metabolic comorbidities such as type II diabetes occur with a higher rate in people with OA than in the general population. Several factors including obesity, hyperglycaemia toxicity and physical inactivity have been suggested as potential links between diabetes and OA, and have been shown to negatively impact patients' health and quality of life. However, little is known on the role of diabetes in determining the outcome of non-surgical and surgical management of OA, and at the same time, how different OA interventions may affect diabetes control. Thus, the overall aim of this project is to explore (1) the impact of diabetes on the outcome of non-surgical and surgical OA treatments and (2) the impact of non-surgical and surgical OA treatments on diabetes control. Methods and analysis The study cohort is based on prospectively ascertained register data on a national level in Sweden. Data from OA patients who received a first-line non-surgical intervention and are registered in the National Quality Register for Better Management of Patients with Osteoarthritis will be merged with data from the Swedish Knee and Hip Arthroplasty Registers and the National Diabetes Register. Additional variables regarding patients' use of prescribed drugs, comorbidities, socioeconomic status and cause of death will be obtained through other national health and population data registers. The linkage will be performed on an individual level using unique personal identity numbers. Ethics and dissemination This study received ethical approval (2019-02570) from the Swedish Ethical Review Authority. Results from this cohort will be submitted to peer-reviewed scientific journals and reported at the leading national and international meetings in the field.
32.	Akerstrom, B., et al. (författare) Structural relationship between α1-microglobulin from man, guinea-pig, rat and rabbit 1988 Ingår i: European Journal of Biochemistry. - 0014-2956. ; 170:1-2, s. 143-148 Tidskriftsartikel (refereegranskat)abstract Rabbit α1-microglobulin was purified from the urine of sodium-chromate-treated animals by the use of gel chromatography on Sephadex G-100 affinity chromatography on concanavalin-A - Sepharose and ion-exchange chromatography on DEAE-Sephadex. Rabbit α1-microglobulin had a molecular mass of 25.6 kDa on SDS/polyacrylamide gel electrophoresis. α1-microglobulin has previously been purified from the urine of humans, guinea-pigs and rats by similar methods, and the molecular masses of the four homologues were compared by SDS/polyacrylamide gel electrophoresis and gel chromatography in a denaturing medium. By these two methods the human homologue was 6 kDa and 3 kDa larger, respectively, than the other three proteins. Endoglycosidase F digestion of α1-microglobulin, followed by SDS/polyacrylamide gel electrophoresis, revealed three protein bands in the human α1-microglobulin sample, and only two bands in guinea-pig, rat and rabbit α1-microglobulin, with a gap between each band of 2.6-2.9 kDa. The amino-terminal amino acid sequences of the four homologues were determined and between 72% and 81% homology was seen. The five amino-terminal amino acids present in the other species were missing in guinea-pig α1-microglobulin. Our results indicate that human α1-microglobulin is substituted with two N-linked oligosaccharides, while only one is attached to each of the other α1-microglobulins, and that the extra glycosylamine-linked oligosaccharide in the human protein is attached to asparagine in position 17. Finally it is shown that all four homologues inhibit antigen stimulation of human lymphocytes, a finding which is consistent with our previous suggestion that the N-linked oligosaccharides carry the immunosuppressive activity of α1-microglobulin.
33.	Allori, AC, et al. (författare) A Standard Set of Outcome Measures for the Comprehensive Appraisal of Cleft Care 2017 Ingår i: The Cleft palate-craniofacial journal : official publication of the American Cleft Palate-Craniofacial Association. - : SAGE Publications. - 1545-1569. ; 54:5, s. 540-554 Tidskriftsartikel (refereegranskat)abstract Care of the patient with cleft lip and/or palate remains complex. Prior attempts at aggregating data to study the effectiveness of specific interventions or overall treatment protocols have been hindered by a lack of data standards. There exists a critical need to better define the outcomes- particularly those that matter most to patients and their families-and to standardize the methods by which these outcomes will be measured. This report summarizes the recommendations of an international, multidisciplinary working group with regard to which outcomes a typical cleft team could track, how those outcomes could be measured and recorded, and what strategies may be employed to sustainably implement a system for prospective data collection. It is only by agreeing on a common, standard set of outcome measures for the comprehensive appraisal of cleft care that intercenter comparisons can become possible. This is important for quality-improvement endeavors, comparative effectiveness research, and value-based health-care reform.
34.	Aspenberg, P., et al. (författare) Fibroblast growth factor increases or inhibits induced bone formation, depending on dose 1991 Ingår i: Acta Orthopaedica Scandinavica. Supplementum. - 0300-8827. ; 62:246, s. 35-35 Tidskriftsartikel (refereegranskat)
35.	Beard, David J., et al. (författare) Placebo comparator group selection and use in surgical trials : The aspire project including expert workshop 2021 Ingår i: Health Technology Assessment. - 1366-5278. ; 25:53 Tidskriftsartikel (refereegranskat)abstract Background: The use of placebo comparisons for randomised trials assessing the efficacy of surgical interventions is increasingly being considered. However, a placebo control is a complex type of comparison group in the surgical setting and, although powerful, presents many challenges. Objectives: To provide a summary of knowledge on placebo controls in surgical trials and to summarise any recommendations for designers, evaluators and funders of placebo-controlled surgical trials. Design: To carry out a state-of-the-art workshop and produce a corresponding report involving key stakeholders throughout. Setting: A workshop to discuss and summarise the existing knowledge and to develop the new guidelines. Results: To assess what a placebo control entails and to assess the understanding of this tool in the context of surgery is considered, along with when placebo controls in surgery are acceptable (and when they are desirable). We have considered ethics arguments and regulatory requirements, how a placebo control should be designed, how to identify and mitigate risk for participants in these trials, and how such trials should be carried out and interpreted. The use of placebo controls is justified in randomised controlled trials of surgical interventions provided that there is a strong scientific and ethics rationale. Surgical placebos might be most appropriate when there is poor evidence for the efficacy of the procedure and a justified concern that results of a trial would be associated with a high risk of bias, particularly because of the placebo effect. Conclusions: The use of placebo controls is justified in randomised controlled trials of surgical interventions provided that there is a strong scientific and ethics rationale. Feasibility work is recommended to optimise the design and implementation of randomised controlled trials. An outline for best practice was produced in the form of the Applying Surgical Placebo in Randomised Evaluations (ASPIRE) guidelines for those considering the use of a placebo control in a surgical randomised controlled trial. Limitations: Although the workshop participants involved international members, the majority of participants were from the UK. Therefore, although every attempt was made to make the recommendations applicable to all health systems, the guidelines may, unconsciously, be particularly applicable to clinical practice in the UK NHS. Future work: Future work should evaluate the use of the ASPIRE guidelines in making decisions about the use of a placebo-controlled surgical trial. In addition, further work is required on the appropriate nomenclature to adopt in this space.
36.	Bergman, B., et al. (författare) Morphologic and autoradiographic observations on the effect of zinc deficiency on endochondral growth sites in the white rat. 1970 Ingår i: Odontologisk revy. - 0029-8441. ; 21:4, s. 379-399 Tidskriftsartikel (refereegranskat)
37.	Bergman, B., et al. (författare) The importance of zinc to cell proliferation in endochondral growth sites in the white rat. 1972 Ingår i: Scandinavian Journal of Dental Research. - 0029-845X. ; 80:6, s. 486-492 Tidskriftsartikel (refereegranskat)
38.	Bowes, M. A., et al. (författare) Marked and rapid change of bone shape in acutely ACL injured knees – an exploratory analysis of the Kanon trial 2019 Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 27:4, s. 638-645 Tidskriftsartikel (refereegranskat)abstract Background: To investigate changes in knee 3D bone shape over the first 5 years after acute anterior cruciate ligament (ACL) injury in participants of the randomized controlled KANON-trial. Methods: Serial MR images over 5 years from 121 young (32 women, mean age 26.1 years) adults with an acute ACL tear in a previously un-injured knee were analyzed using statistical shape models for bone. A matched reference cohort of 176 individuals was selected from the Osteoarthritis Initiative (OAI). Primary endpoint was change in bone area of the medial femoral condyle; exploratory analyses compared results by treatment and examined other knee regions. Comparisons were made using repeated measures mixed model ANOVA with adjustment for age, sex and body mass index (BMI). Results: Mean medial femur bone area increased 3.2% (78.0 [95% CI 70.2 to 86.4] mm2) over 5 years after ACL injury and most prominently in knees treated with ACL reconstruction (ACLR). A higher rate of increase occurred over the first 2 years compared to the latter 3-years (66.2 [59.3 to 73.2] vs 17.6 [12.2 to 23.0] mm2) and was 6.7 times faster than in the reference cohort. The pattern and location of shape change in the extrapolated KANON data was very similar to that observed in another knee-osteoarthritis cohort. Conclusion: 3D shape modelling after acute ACL injury revealed rapid bone shape changes, already evident at 3 months. The bone-change pattern after ACL injury demonstrated flattening and bone growth on the outer margins of the condyles similar to that reported in established knee osteoarthritis.
39.	Buckwalter, J. A., et al. (författare) Operative treatment of osteoarthrosis 1994 Ingår i: Journal of Bone and Joint Surgery. American Volume. - 0021-9355. ; 76:9, s. 1405-1418 Tidskriftsartikel (refereegranskat)
40.	Conaghan, P. G., et al. (författare) MRI and non-cartilaginous structures in knee osteoarthritis 2006 Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 14:Suppl. 1, s. 87-94 Tidskriftsartikel (refereegranskat)abstract Magnetic resonance imaging (MRI) provides a sensitive tool for examining all the structures involved in the osteoarthritis (OA) process. While much of the MRI literature previously focussed on cartilage, there is increasing research on whole-organ evaluation and including features such as synovitis, bone marrow edema, and meniscal and ligamentous pathology. The aim of this session at the Outcome Measures in Rheumatology Clinical Trials (OMERACT)-Osteoarthritis Research Society International (OARSI) Workshop for Consensus in Osteoarthritis Imaging was to describe the current MRI methods for identifying and quantifying non-cartilaginous structures and review their associations with both CIA symptoms and structural progression. Although there is much experience in measuring synovitis (derived from the rheumatoid arthritis literature), only one study has reported an association of MRI-detected synovitis and effusions with OA pain. Bone marrow edema lesions, which may represent areas of trabecular remodelling, have been associated with pain and compartment-specific structural deterioration. MRI studies have confirmed the frequency and importance of meniscal damage in progressive cartilage loss, but not related such damage to symptoms. Osteophytes have been associated with cartilage loss and malalignment to the side of the osteophyte. Ligament damage, including anterior cruciate ligament tears, has been found more commonly than expected in painful CA knees. Improvements in quantitative and semi-quantitative assessments of non-cartilage features will greatly assist understanding of the CA process and its response to therapy. (C) 2006 OsteoArthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
41.	Cronström, Anna, et al. (författare) On the waiting list for joint replacement for knee osteoarthritis : are first-line treatment recommendations implemented? 2020 Ingår i: Osteoarthritis and Cartilage Open. - : Elsevier. - 2665-9131. ; 2:2 Tidskriftsartikel (refereegranskat)abstract Objective: To investigate to what extent individuals participated in guideline-based first-line treatments before being assigned to a wait list for knee replacement for osteoarthritis (OA), and to what extent they were recommended such treatments once on the list. Factors associated with participation in first-line management were also investigated.Design: All patients on the waiting list ≥ three months for knee replacement due to knee OA (n = 229) at a public hospital in Sweden were invited to participate in this cross-sectional survey study. 136 individuals (mean age 70 ± 9 years, 59% women) answered self-reported questionnaires including demographics, physical activity level, knee function and treatments before and during their time on the waiting list.Results: Before being referred to the waiting list, 40% had participated in guideline-based OA management (Better management of patients with OsteoArthritis (BOA)), 53% in physiotherapy, 67% in either BOA or physiotherapy whilst 23% of those overweight (BMI≥25) had received weight-management advice. Women had participated in BOA and physiotherapy twice as often as men (51% vs. 25%, p = 0.002 and 66% vs. 34%, p < 0.001) prior to waiting list referral. During their time on the waiting list, only 10% were recommended BOA, 30% physiotherapy and 15% weight-management. 38% of the patients that had never participated in BOA indicated that they were interested in participating while waiting for their knee replacement.Conclusion: Our results suggest that recommended treatment guidelines for OA may not be adequately implemented in Swedish health-care. Further exploration of implementation barriers and lack of equality of care appears warranted.
42.	Dahlberg, L., et al. (författare) A longitudinal study of cartilage matrix metabolism in patients with cruciate ligament rupture-synovial fluid concentrations of aggrecan fragments, stromelysin-1 and tissue inhibitor of metalloproteinase-1 1994 Ingår i: British Journal of Rheumatology. - : Oxford University Press (OUP). - 0263-7103. ; 33:12, s. 1107-1111 Tidskriftsartikel (refereegranskat)abstract This is the first study which quantifies aggrecan fragments, stromelysin-1 and tissue inhibitor of metalloproteinases-1 (TIMP-1) in SF samples prospectively obtained from the same patient at different time intervals after a cruciate ligament injury of the knee. Aggrecan fragment concentrations were determined by dye precipitation with Alcian Blue. Stromelysin-1 and TIMP-1 were analysed by immunoassay. Ten healthy volunteers formed the reference group. Immediately after knee injury, all marker concentrations were higher as compared to the reference group. The high marker concentrations decreased gradually with time, and in samples obtained between 6 months and 6 years after the injury, median concentrations of some of the markers were not different compared to reference levels. This was in contrast to results from previous cross-sectional studies, where chronic phase median concentrations of all markers were consistently higher than reference levels. In previous cross-sectional studies, however, the samples were obtained at arthroscopy done because of knee complaints at different times after a knee injury. In the present study, the knee injured patients visited the orthopaedic outpatient ward only for SF sampling, and they had no or only minor knee symptoms. We conclude that the temporal changes of marker concentrations in joint fluid after knee injury, suggested from cross-sectional studies, have now been confirmed in a longitudinal, prospective cohort study. We further find that in patients with mild knee symptoms in the chronic phase after cruciate ligament injury, median SF levels of aggrecan fragments, stromelysin-1, and TIMP-1 are lower than in patients with significant knee complaints after the same type of injury. This suggests a possible relationship between joint fluid marker concentrations, joint pathology, and cartilage metabolism.
43.	Dahlberg, L., et al. (författare) Authors' reply 1995 Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967. ; 54:8, s. 685-685 Tidskriftsartikel (refereegranskat)
44.	Dahlberg, L., et al. (författare) Cartilage metabolism in the injured and uninjured knee of the same patient 1994 Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967. ; 53:12, s. 823-827 Tidskriftsartikel (refereegranskat)abstract Objective-To examine if unilateral knee injury affects the synovial fluid concentrations of aggrecan fragments, cartilage oligomeric matrix protein (COMP) fragments, stromelysin-l, and tissue inhibitor of metalloproteinases-l (TIMP-1) in the contralateral uninjured knee. Methods-Synovial fluids from the injured and uninjured knees were obtained at different times in a group of patients after unilateral knee trauma. Serum samples were obtained on the same occasion. Concentrations of aggrecan fragments were determined by precipitation with Alcian Blue; those of COMP fragments, stromelysin-l, and TIMP-1 were measured by immunoassay. Concentrations were compared with those in a reference group of 10 healthy volunteers. Results-Immediately after knee injury, concentrations of aggrecan fragments, COMP fragments, stromelysin-l and TIMP-1 were increased in the synovial fluid of the injured knee. However, concentrations of aggrecan and COMP fragments, and stromelysin-l increased also in the contralateral uninjured knee immediately after injury, but less than in the injured knee. Subsequently, the concentrations ofall markers decreased in the synovial fluid of the injured knee, but remained unchanged in the uninjured knee. The concentration of aggrecan fragments in the injured knee decreased to less than that in the uninjured knee in the chronic phase. Serum concentrations of COMP were much smaller than those in synovial fluid. Conclusions-The increased concentrations of aggrecan and COMP fragments and stromelysin-1 in the joint fluid of the contralateral, uninjured knee following unilateral knee injury, compared with concentrations in healthy reference knees, suggest changes in joint cartilage metabolism in both knees following unilateral knee injury. The mechanisms for these changes are unclear. The low serum concentration of COMP makes it less likely that there is any significant 'exchange' of molecular markers between the knees. A further consequence of these findings is that the contralateral knee cannot be recommended as the only control joint in studies of matrix metabolism in patients with unilateral knee injury.
45.	de Luca, S., et al. (författare) Proteoglycans from chick limb bud chondrocyte cultures. Keratan sulfate and oligosaccharides which contain mannose and sialic acid 1980 Ingår i: Journal of Biological Chemistry. - 0021-9258. ; 255:13, s. 6077-6083 Tidskriftsartikel (refereegranskat)abstract The precursors, [ 35S]sulfate and [2- 3H]mannose, were used to study the biosynthesis of keratan sulfate and other oligosaccharides on proteoglycans isolated from Day 8 cultures of chick limb bud chondrocytes. After alkaline borohydride treatment, three fractions with sialic acid were separated by molecular sieve chromatography. The first contained keratan sulfate which was purified by digestion with chondroitinase to remove chondroitin sulfate, followed by molecular sieve and ion exchange chromatography. The purified keratan sulfate contained about 8% of the 35S activity originally in monomer. The chains had an average length of about 40 monosaccharides and contained only trace amounts of mannose (less than 1 residue/three to four chains). The second fraction contained the majority of the [ 3H]mannose originally in monomer, but no 35S activity. This fraction appears to contain oligosaccharide-peptides of the asparagine-N-glycosylamine type because there were no reduced sugars present and the alkaline borohydride treatment extensively degraded the core protein. The composition of the oligosaccharides, with high proportions of mannose, N-acetylglucosamine, galactose, and sialic acid, was consistent with this suggestion. The third fraction consisted of a series of oligosaccharides with sizes between three to six saccharides. They contained N-acetylgalactosaminitol, indicating that they were attached to the core protein by O-glycoside bonds between N-acetylgalactosamine and hydroxyl groups on serine and threonine. Thus, proteoglycans contain two classes of oligosaccharides, a mannose-rich class characteristic of glycoproteins and an O-glycoside class characteristic of mucins, in addition to the chondroitin sulfate and keratan sulfate chains.
46.	Dieppe, P., et al. (författare) Detecting and measuring disease modification in osteoarthritis. The need for standardized methodology 1995 Ingår i: Journal of Rheumatology. - 0315-162X. ; 22:2, s. 201-203 Tidskriftsartikel (refereegranskat)
47.	Dowsey, M. M., et al. (författare) Variations in pain and function before and after total knee arthroplasty : A comparison between Swedish and Australian cohorts 2017 Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 25:6, s. 885-891 Tidskriftsartikel (refereegranskat)abstract Objective: Preoperative pain and function is viewed as an important predictor of total knee arthroplasty (TKA) outcomes. We examined whether variations in pain and function outcomes existed at 12 months between two centres in Sweden and Australia, and whether this was explained by variations in patient presentation for TKA. Methods: This was a retrospective analysis of prospectively collected data. Patients from one centre in Australia (St. Vincent's Hospital (SVH), N = 516) and in Sweden (Trelleborg (TBG), N = 899) who underwent primary TKA between 2012 and 2013. The Western Ontario and McMaster Universities Arthritis Index (WOMAC) was analysed pre- and 12 months' post TKA from which non-response to surgery was determined using the OMERACT-OARSI criteria. Multiple linear regression analysis was used to examine the relationship between change in pain and function and surgery centre, adjusting for preoperative patient characteristics and surgical technique. Results: Despite worse preoperative outcomes in all subscales of the WOMAC for the SVH cohort, there were no clinically meaningful differences in 12-month WOMAC subscales nor change in WOMAC subscales between SVH and TBG. Almost identical proportions of patients were considered OMERACT-OARSI responders, 85.7% (SVH) and 85.9% (TBG), however for the SVH cohort 25 (4.9%) were moderate and 417 (80.8%) were high responders, compared to the TBG cohort of which 225 (25%) were moderate and 547 (60.9%) were high responders. Conclusion: Despite differences in preoperative presentation between 2 countries, improvements in pain and function and the proportion of individual who responded to TKA surgery at 1 year were similar. Factors related to poor response to TKA surgery require further elucidation.
48.	Ekman, B, et al. (författare) Costing analysis of a digital first-line treatment platform for patients with knee and hip osteoarthritis in Sweden 2020 Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 15:8, s. 0236342-0236342 Tidskriftsartikel (refereegranskat)abstract Osteoarthritis (OA) constitutes a major and increasing burden on patients, health care systems and the broader society. It is estimated that around a quarter of the adult population is affected by OA in the knee and hip and that the prevalence of OA will increase over the coming decades largely due to aging and adverse life-style factors. Prevention and effective care are critical to manage the challenges posed by OA. Digital technologies offer opportunities to deliver cost-effective care for chronic diseases, including for OA. We report the results of a costing analysis of a new digital platform for delivering first-line care including disease information and physiotherapy to patients with OA and compare this with an existing face-to-face model of treatment. Both models are in accordance with National Treatment Guidelines in Sweden. The results show that overall the digital model costs around 25% of the existing face-to-face model of care. Based on existing evidence on the effects of these models, our findings also suggest that the digital platform offers a cost-effective alternative to the existing model of OA care. Depending on the extent to which the digital model substitutes for the existing model of care, significant resources can be saved.
49.	Englund, M, et al. (författare) Patient-relevant outcomes fourteen years after meniscectomy : influence of type of meniscal tear and size of resection 2001 Ingår i: Rheumatology. - : Oxford University Press (OUP). - 1462-0332 .- 1462-0324. ; 40:6, s. 631-639 Tidskriftsartikel (refereegranskat)abstract OBJECTIVES: To study long-term patient-relevant outcomes after meniscectomy, a surgical procedure associated with a high risk of knee osteoarthritis (OA). Principal objectives were to compare traumatic with degenerative meniscal tear and partial with subtotal meniscectomy.METHODS: We studied a well-defined cohort of 205 patients who had undergone isolated unilateral meniscectomy between 1983 and 1985. There was no previous knee surgery and all knees were stable. The type of meniscal tear and surgical resection was ascertained by review of medical records. Patients were followed up after 14 yr (range 12-15 yr) by self-administered questionnaires, one generic [Short Form 36 (SF-36)] and one disease-specific [Knee Injury and Osteoarthritis Outcome Score (KOOS)].RESULTS: In a multivariate analysis, using the Sports and Recreation Function and knee-related Quality of Life subscales of the KOOS questionnaire as dependent variables, patients with a degenerative tear scored significantly worse than individuals with a traumatic tear (P < or = 0.001). When we analysed unmatched subgroups and age- and sex-matched patients with degenerative or traumatic lesions, the same result was found for the knee-specific outcome (P < or = 0.02) and SF-36 except for Social Functioning (P < or = 0.04). There was no difference in outcome for the total cohort according to the type of resection. However, subgroup analyses showed that patients who underwent subtotal meniscectomy for a degenerative tear scored significantly worse on the knee-specific outcome than individuals who had had a partial meniscectomy for the same type of tear (P < or = 0.02).CONCLUSIONS: The long-term outcome of meniscal injury and surgery appears to be determined largely by the type of meniscal tear. Furthermore, our findings support the use of minimal meniscal resection in the treatment of degenerative tears. We suggest that the disease processes associated with the development of OA of the joint cartilage may also be active in the meniscus, and that a tear in a meniscus with degenerative changes might be regarded as the first sign of OA of the joint.
50.	Evangelou, Evangelos, et al. (författare) A meta-analysis of genome-wide association studies identifies novel variants associated with osteoarthritis of the hip 2014 Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 73:12, s. 2130-2136 Tidskriftsartikel (refereegranskat)abstract Objectives Osteoarthritis (OA) is the most common form of arthritis with a clear genetic component. To identify novel loci associated with hip OA we performed a meta-analysis of genome-wide association studies (GWAS) on European subjects. Methods We performed a two-stage meta-analysis on more than 78 000 participants. In stage 1, we synthesised data from eight GWAS whereas data from 10 centres were used for 'in silico' or 'de novo' replication. Besides the main analysis, a stratified by sex analysis was performed to detect possible sex-specific signals. Meta-analysis was performed using inverse-variance fixed effects models. A random effects approach was also used. Results We accumulated 11 277 cases of radiographic and symptomatic hip OA. We prioritised eight single nucleotide polymorphism (SNPs) for follow-up in the discovery stage (4349 OA cases); five from the combined analysis, two male specific and one female specific. One locus, at 20q13, represented by rs6094710 (minor allele frequency (MAF) 4%) near the NCOA3 (nuclear receptor coactivator 3) gene, reached genome-wide significance level with p=7.9x10(-9) and OR=1.28 (95% CI 1.18 to 1.39) in the combined analysis of discovery (p= 5.6x10(-8)) and follow-up studies (p=7.3x10(-4)). We showed that this gene is expressed in articular cartilage and its expression was significantly reduced in OA-affected cartilage. Moreover, two loci remained suggestive associated; rs5009270 at 7q31 (MAF 30%, p=9.9x10(-7), OR=1.10) and rs3757837 at 7p13 (MAF 6%, p=2.2x10(-6), OR=1.27 in male specific analysis). Conclusions Novel genetic loci for hip OA were found in this meta-analysis of GWAS.

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