| 1. |
- Watt, F. E., et al.
(författare)
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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
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Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 27:1, s. 23-33
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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.
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| 2. |
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| 3. |
- Styrkarsdottir, Unnur, et al.
(författare)
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Whole-genome sequencing identifies rare genotypes in COMP and CHADL associated with high risk of hip osteoarthritis
- 2017
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 49:5, s. 801-805
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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.
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| 4. |
- Semb, G, et al.
(författare)
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Erratum
- 2017
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Ingår i: Journal of plastic surgery and hand surgery. - 2000-6764. ; 51:2, s. 158-158
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Tidskriftsartikel (refereegranskat)
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| 5. |
- Chockalingam, P. S., et al.
(författare)
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Elevated aggrecanase activity in a rat model of joint injury is attenuated by an aggrecanase specific inhibitor
- 2011
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Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 19:3, s. 315-323
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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.
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| 6. |
- Chockalingam, P. S., et al.
(författare)
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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
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Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 21:2, s. 339-345
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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.
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| 7. |
- Kerkhof, H. J. M., et al.
(författare)
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Recommendations for standardization and phenotype definitions in genetic studies of osteoarthritis: the TREAT-OA consortium
- 2011
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Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 19:3, s. 254-264
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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.
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| 8. |
- Leyland, K. M., et al.
(författare)
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Harmonising measures of knee and hip osteoarthritis in population-based cohort studies : an international study
- 2018
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Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 26:7, s. 872-879
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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.
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| 9. |
- Meneses, S. R F, et al.
(författare)
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Clinical algorithms to aid osteoarthritis guideline dissemination
- 2016
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Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 24:9, s. 1487-1499
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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.
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| 10. |
- Styrkarsdottir, Unnur, et al.
(författare)
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GWAS of bone size yields twelve loci that also affect height, BMD, osteoarthritis or fractures
- 2019
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1
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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.
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| 11. |
- Willadsen, E., et al.
(författare)
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Scandcleft randomized trials of primary surgery for unilateral cleft lip and palate: Speech proficiency at 10 years of age
- 2023
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Ingår i: International journal of language and communication disorders. - : WILEY. - 1368-2822 .- 1460-6984. ; 58:3, s. 892-909
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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.
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| 12. |
- Zhang, W., et al.
(författare)
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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
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Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 18:4, s. 476-499
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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.
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| 13. |
- Ahlin, Sofie, 1985, et al.
(författare)
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Fracture risk after three bariatric surgery procedures in Swedish obese subjects : up to 26 years follow-up of a controlled intervention study
- 2020
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 287:5, s. 546-557
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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.
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| 14. |
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| 15. |
- Bannuru, R. R., et al.
(författare)
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OARSI guidelines for the non-surgical management of knee, hip, and polyarticular osteoarthritis
- 2019
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Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584.
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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.
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| 16. |
- Eyles, J.P., et al.
(författare)
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Clinical Outcomes Of Osteoarthritis Management Programs: A Project Of The Oa Trial Bank And Oarsi Joint Effort Initiative Using Individual Participant Data
- 2023
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Ingår i: Osteoarthritis and Cartilage. - : Elsevier. - 1063-4584 .- 1522-9653. ; 31, s. S385-S386
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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.
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| 17. |
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| 18. |
- Kraus, V. B., et al.
(författare)
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Application of biomarkers in the development of drugs intended for the treatment of osteoarthritis
- 2011
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Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 19:5, s. 515-542
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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.
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| 19. |
- Larsson, S., et al.
(författare)
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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
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Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 25:9, s. 1443-1451
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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.
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| 20. |
- Lohmander, L. S., et al.
(författare)
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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
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Ingår i: Osteoarthritis and cartilage. - : Elsevier BV. - 1522-9653 .- 1063-4584. ; 31:5, s. 636-646
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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.
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| 21. |
- Lohmander, L. S., et al.
(författare)
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Stromelysin, tissue inhibitor of metalloproteinases and proteoglycan fragments in human knee joint fluid after injury
- 1993
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Ingår i: Journal of Rheumatology. - 0315-162X. ; 20:8, s. 1362-1368
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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.
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| 22. |
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| 23. |
- Luyten, F. P., et al.
(författare)
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Toward classification criteria for early osteoarthritis of the knee
- 2018
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Ingår i: Seminars in Arthritis and Rheumatism. - : Elsevier BV. - 0049-0172. ; 47:4, s. 457-463
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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.
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| 24. |
- Mehta, S. P., et al.
(författare)
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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
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Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 24:12, s. 2077-2081
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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.
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| 25. |
- Moskalewski, S., et al.
(författare)
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Influence of colchicine and vinblastine on the Golgi complex and matrix deposition in chondrocyte aggregates. An ultrastructural study
- 1975
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Ingår i: Experimental Cell Research. - : Elsevier BV. - 0014-4827. ; 95:2, s. 440-454
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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.
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