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Sökning: WFRF:(Lohmander Stefan)

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  • Evangelou, Evangelos, et al. (författare)
  • Meta-analysis of genome-wide association studies confirms a susceptibility locus for knee osteoarthritis on chromosome 7q22
  • 2011
  • Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 70:2, s. 349-355
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives Osteoarthritis (OA) is the most prevalent form of arthritis and accounts for substantial morbidity and disability, particularly in older people. It is characterised by changes in joint structure, including degeneration of the articular cartilage, and its aetiology is multifactorial with a strong postulated genetic component. Methods A meta-analysis was performed of four genome-wide association (GWA) studies of 2371 cases of knee OA and 35 909 controls in Caucasian populations. Replication of the top hits was attempted with data from 10 additional replication datasets. Results With a cumulative sample size of 6709 cases and 44 439 controls, one genome-wide significant locus was identified on chromosome 7q22 for knee OA (rs4730250, p = 9.2 x 10(-9)), thereby confirming its role as a susceptibility locus for OA. Conclusion The associated signal is located within a large (500 kb) linkage disequilibrium block that contains six genes: PRKAR2B (protein kinase, cAMP-dependent, regulatory, type II, beta), HPB1 (HMG-box transcription factor 1), COG5 (component of oligomeric golgi complex 5), GPR22 (G protein-coupled receptor 22), DUS4L (dihydrouridine synthase 4-like) and BCAP29 (B cell receptor-associated protein 29). Gene expression analyses of the (six) genes in primary cells derived from different joint tissues confirmed expression of all the genes in the joint environment.
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  • 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.
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  • Abrahamsson, Sven Olof, et al. (författare)
  • Dehydration inhibits matrix synthesis and cell proliferation : An in vitro study of rabbit flexor tendons
  • 1991
  • Ingår i: Acta Orthopaedica. - : Medical Journals Sweden AB. - 1745-3674 .- 0001-6470. ; 62:2, s. 159-162
  • Tidskriftsartikel (refereegranskat)abstract
    • Segments of the deep flexor tendon of the rabbit were exposed to air; the effects of dehydration on in vitro synthesis of proteoglycan, collagen, non-collagenous protein, and cell proliferation were compared with tendon segments that were kept moist with physiologic saline. After 20 min of expo-sure to air, the tendons lost half and after 40 min all of their ability to synthesize matrix components and to proliferate, whereas irrigated tendons remained viable during the entire experiment.
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  • Abrahamsson, Sven Olof, et al. (författare)
  • Variations in cellular proliferation and matrix synthesis in intrasynovial and extrasynovial tendons : An in vitro study in dogs
  • 1994
  • Ingår i: The Journal of Hand Surgery. - : Elsevier BV. - 0363-5023. ; 19:2, s. 259-265
  • Tidskriftsartikel (refereegranskat)abstract
    • Intrasynovial and extrasynovial flexor tendon grafts recently have been shown to have dissimilar patterns of cellular survival and host integration within the digital sheath. In an effort to determine if fundamental differences exist between these two types of tendons, we investigated the biochemical composition and cellular activity of intrasynovial and extrasynovial tendon segments of 12 adult mongrel dogs in short-term explant culture in MCDB 105 and in DMEM media. Proteoglycan, collagen and noncollagen protein synthesis and content and DNA synthesis were determined following culture in both media. Intrasynovial tendon segments cultured in MCDB 105 medium synthesized significantly less collagen, noncollagen protein, and DNA and had similar amounts of proteoglycans compared to extrasynovial tendons. Comparison of intrasynovial and extrasynovial tendon segment responses in DMEM medium showed that intrasynovial tendons synthesized more proteoglycan, protein, and DNA than they did in MCDB 105. Extrasynovial tendons had similar rates of matrix component and DNA synthesis in both media. Findings that the synthesis of matrix components and DNA between intrasynovial flexor and extrasynovial peroneal tendon segments differ significantly indicate that intrasynovial flexor tendons may be specially adapted to the nutritional milieu provided by an intrasynovial environment. These data are supported by the selective successful stimulation of fibrocartilaginous segments within intrasynovial flexor tendons in media favored for the culture of cartilaginous tissue.
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  • Ageberg, Eva, et al. (författare)
  • Effect of leisure time physical activity on severe knee or hip osteoarthritis leading to total joint replacement: a population-based prospective cohort study
  • 2012
  • Ingår i: BMC Musculoskeletal Disorders. - : Springer Science and Business Media LLC. - 1471-2474. ; 13:73
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Studies on leisure time physical activity as risk factor or protective factor for knee or hip osteoarthritis (OA) show divergent results. Longitudinal prospective studies are needed to clarify the association of physical activity with future OA. The aim was to explore in a prospective population-based cohort study the influence of leisure time physical activity on severe knee or hip OA, defined as knee or hip replacement due to OA. Methods: Leisure time physical activity was reported by 28320 participants (mean age 58 years (SD 7.6), 60% women) at baseline. An overall leisure time physical activity score, taking both duration and intensity of physical activities into account, was created. The most commonly reported activities were also used for analysis. The incidence of knee or hip replacement due to OA over 11 years was monitored by linkage with the Swedish hospital discharge register. Cox's proportional hazards model (crude and adjusted for potential confounding factors) was used to assess the incidence of total joint replacement, or osteotomy (knee), in separate analyses of leisure time physical activity. Results: There was no significant overall association between leisure time physical activity and risk for knee or hip replacement due to OA over the 11-year observation time. For women only, the adjusted RR (95% CI) for hip replacement was 0.66 (0.48, 0.89) (fourth vs. first quartile), indicating a lower risk of hip replacement in those with the highest compared with the lowest physical activity. The most commonly reported activities were walking, bicycling, using stairs, and gardening. Walking was associated with a lower risk of hip replacement (adjusted RR 0.76 (95% CI 0.61, 0.94), specifically for women (adjusted RR 0.75 (95% CI 0.57, 0.98)). Conclusions: In this population-based study of middle-aged men and women, leisure time physical activity showed no consistent overall relationship with incidence of severe knee or hip OA, defined as joint replacement due to OA, over 11 years. For women, higher leisure time physical activity may have a protective role for the incidence of hip replacement. Walking may have a protective role for hip replacement, specifically for women.
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  • Ahmad Kiadaliri, Aliasghar, et al. (författare)
  • Association of knee pain and different definitions of knee osteoarthritis with health-related quality of life : A population-based cohort study in southern Sweden
  • 2016
  • Ingår i: Health and Quality of Life Outcomes. - : Springer Science and Business Media LLC. - 1477-7525. ; 14:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: While the impact of knee pain and knee osteoarthritis (OA) on health-related quality of life (HRQoL) has been investigated in the literature, there is a lack of knowledge on the impact of different definitions of OA on HRQoL. The main aim of this study was to measure and compare the impact of knee OA and its different definitions on HRQoL in the general population. Methods: A random sample of 1300 participants from Malmö, Sweden with pain in one or both knees in the past 12 months with duration ≥4 weeks and 650 participants without were invited to clinical and radiographic knee examination. A total of 1527 individuals with a mean (SD) age 69.4 (7.2) participated and responded to both generic (EQ-5D-3L) and disease-specific (the Knee injury and Osteoarthritis Outcome Score) questionnaires. Knee pain was defined as pain during the last month during most of the days. Knee OA was defined radiographically (equivalent to Kellgren and Lawrence grade ≥2) and clinically according to the American College of Rheumatology (ACR) criteria. Results: Of participants with either knee pain or knee OA or both, 7 % reported no problem for the EQ-5D-3L attributes. The corresponding proportion among references (neither knee pain nor OA) was 42 %. The participants with knee pain and OA had all HRQoL measures lower compared to those with knee pain but no OA. The ACR clinical definition of knee OA was associated with lower HRQoL than the definition based on radiographic knee OA (adjusted difference -0.08 in UK EQ-5D-3L index score). Conclusions: Applying different definitions of knee OA result in different levels of HRQoL and this is mainly explained by the knee pain experience. These differences may lead to discrepant conclusions from cost-utility analyses.
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  • Altman, RD, et al. (författare)
  • Measurement of structural progression in osteoarthritis of the hip: the Barcelona consensus group
  • 2004
  • Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 12:7, s. 515-524
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To outline the best available method of measurement for detecting progression of osteoarthritis (OA) of the hip especially in therapeutic trials. Method A Medline search of articles related to progression of hip CA was performed. A group of experts met over a 1.5-day session to review available literature and new research. Specific questions were addressed in order to reach a consensus on measuring progression of CA of the hip. Results: Of the available surrogate measures, a single yearly standing or reclined antero-posterior plain radiograph of the pelvis with feet internally rotated 15-20degrees, can be evaluated with the use of an atlas for joint space width (JSW, interbone distance). There should be a minimum JSW upon baseline screening that may be 1 or 2 mm. Digitization of films offers a slight reduction in variability of measurements. Progression of OA can be calculated by measurement of the JSW on paired and blinded films. A reduction of greater than or equal to0.5 mm is greater than the 'minimum perceptible difference' as well as the variation of most imaging techniques, and represents a clinically relevant and significant reduction in the JSW. Narrowing of the superomedial or superolateral JSW may tend to progress more rapidly than other changes. In clinical trials, patients who discontinue the study treatment need to be followed after discontinuation, and an imputation strategy which provides unbiased estimates of both the treatment effect and its variance is an appropriate technique for intent-to-treat analysis. Conclusion: For the development of new agents intended to prevent, retard, stabilize or reverse the progress of CA of the hip, the radiographic methodology presently available is adequate to detect changes in hip JSW of OA.
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  • Andersson, Elin, et al. (författare)
  • Quantification of chondroitin sulfate, hyaluronic acid and N-glycans in synovial fluid – A technical performance study
  • 2023
  • Ingår i: Osteoarthritis and Cartilage Open. - 2665-9131. ; 5:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To validate a quantitative high performance liquid chromatography (HPLC) assay for chondroitin sulfate (CS) and hyaluronic acid (HA) in synovial fluid, and to analyze glycan-patterns in patient samples. Design: Synovial fluid from osteoarthritis (OA, n = 25) and knee-injury (n = 13) patients, a synovial fluid pool (SF-control) and purified aggrecan, were chondroitinase digested and together with CS- and HA-standards fluorophore labelled prior to quantitative HPLC analysis. N-glycan profiles of synovial fluid and aggrecan were assessed by mass spectrometry. Results: Unsaturated uronic acid and sulfated-N-acetylgalactosamine (ΔUA-GalNAc4S and ΔUA-GalNAc6S) contributed to 95% of the total CS-signal in the SF-control sample. For HA and the CS variants in SF-control the intra- and inter-experiment coefficient of variation was between 3–12% and 11–19%, respectively; tenfold dilution gave recoveries between 74 and 122%, and biofluid stability test (room temperature storage and freeze-thaw cycles) showed recoveries between 81 and 140%. Synovial fluid concentrations of the CS variants ΔUA-GalNAc6S and ΔUA2S-GalNAc6S were three times higher in the recent injury group compared to the OA group, while HA was four times lower. Sixty-one different N-glycans were detected in the synovial fluid samples, but there were no differences in levels of N-glycan classes between patient groups. The CS-profile (levels of ΔUA-GalNAc4S and ΔUA-GalNAc6S) in synovial fluid resembled that of purified aggrecan from corresponding samples; the contribution to the N-glycan profile in synovial fluid from aggrecan was low. Conclusions: The HPLC-assay is suitable for analyzing CS variants and HA in synovial fluid samples, and the GAG-pattern differs between OA and recently knee injured subjects.
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  • Andersson, Elin, et al. (författare)
  • Quantification of chondroitin sulfates and hyaluronan in synovial fluid using high performance liquid chromatography
  • 2022
  • Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 30:Suppl 1, s. 106-106
  • Konferensbidrag (refereegranskat)abstract
    • Purpose: Extracellular proteins such as aggrecan may be primed with specific glycan-patterns which result in their degradation, and hence may play a role in the pathogenesis of osteoarthritis (OA). To be able to use glycans as molecular biomarkers, the method of analysis of these molecules needs to be validated. The primary aim of this study was to validate quantitative high performance liquid chromatography (HPLC) of chondroitin sulfate (CS) and hyaluronan (HA) in synovial fluid samples. The secondary aim was to examine the glycan-pattern in different subject groups, and the correlation between age and the concentration of specific glycans.Methods: OA (n=25, age=36-86 years, 40% women) and recent knee injury patients (0-5 days from injury; n=13, age=36-64 years, 46% women) were selected from a cross-sectional convenience cohort. Individual synovial fluid samples, a synovial fluid pool (SF-control; n=7) and a CS quality control sample (CS-QC; Sigma #C2905) were digested with chondroitinase ABC overnight. Samples and glycan standards (CS [n=8] and HA [n=1] standards from Iduron) were labelled with 2-aminoacridone (AMAC) and analyzed using a quantitative HPLC assay. Aggrecan from synovial fluid samples (n=6) was purified using density centrifugation (D1 mini-prep). Sulfated glycosaminoglycans (sGAG) were quantified using Alcian blue precipitation. Since the CS, HA and sGAG data were not normally distributed, non-parametric analyses for group comparisons were done. P-values less than 0.05 were considered statistically significant.Results: Synovial fluid samples were digested with varying concentrations of chondroitinase ABC and analyzed with the HPLC assay; 5 mU chondroitinase ABC per μg sGAG gave the highest CS- and HA-signals and were chosen for the rest of the study (data not shown).The CS profiles in synovial fluid and on aggrecan purified from corresponding synovial fluids were assessed from six knee injury patients. Of the six CS-markers that were detected, uronic acid (UA)-N-acetylgalactosamine (GalNAc) was only present in aggrecan samples, while UA2S-GalNAc and UA2S-GalNAc6S were found only in the synovial fluids. Similar proportions of UA-GalNAc4S and UA-GalNAc6S were found in synovial fluids and aggrecan samples (Figure 1), and these CS-glycans accounted for 95% of all glycans in the SF-control sample (Table 1).The technical performance of CS- and HA-markers using HPLC-assay were evaluated (Table 1). Of the nine markers, five were present in the majority of the synovial fluid samples (N=20-38) and included in the investigation of the technical performance. The mean intra coefficient of variation (CV) for the synovial fluid samples was between 1.2 and 12.9%. For the SF-control sample, the mean intra CV was 3.3-12.1% and the inter CV was 11.0-18.5%. For the CS-QC sample, the mean intra CV was 2.5-9.5% and the mean inter CV was 3.3-31.7%. For the glycan standards, the mean intra CV was 0.2-7.0%. With dilution of the SF-control sample up to 1:10, the dilution recovery rate for the five CS- and HA-markers was mainly between 75 and 125%.The synovial fluid concentration of biomarkers UA-GalNAc6S and UA2s-GalNAc6s and sGAG were approximately 2 to 3 times higher for the recent injury group compared to the age-matched OA group, while the HA levels were 3.7 times lower for the recent injury group (data not shown). No difference in biomarker concentrations were found between the sexes in any of the patient groups (data not shown). For correlation assessments, the two patient groups were merged (total N=38, assessment N = between 20 and 38). Synovial fluid concentrations of HA and UA-GalNAc4S,6S correlated positively with age (rS=0.420 and 0.532, respectively) while UA-GalNAc6S and sGAG correlated negatively with age (rS=-0.333 and -0.528, respectively). HA correlated negatively with UA-GalNAc6S (rS=-0.462) and sGAG (rS=-0.472) and positively with UA-GalNAc4S,6S (rS=0.868).Conclusions: The technical performance of the HPLC-assay indicates that the method is suitable for analyzing CS and HA markers in synovial fluid samples. Our results suggest that: the vast majority of CS in synovial fluid derives from aggrecan, the glycan pattern differs between OA and knee injured subjects and that the concentrations of some of the CS-markers seem to be associated with HA and age.
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17.
  • Aspenberg, P., et al. (författare)
  • Drug test chamber : a titanium implant for administration of biochemical agents to a standardized bone callus in situ
  • 1988
  • Ingår i: Journal of Biomedical Engineering. - : Elsevier BV. - 0141-5425. ; 10:1, s. 70-73
  • Tidskriftsartikel (refereegranskat)abstract
    • A titanium implant in which a conduit is gradually filled with ingrowing bone (the Bone Harvest Chamber) has been modified to allow continuous local treatment of the conduit tissue with biochemical agents. Implants were inserted bilaterally in rabbit tibiae. The tissue content of the bone ingrowth conduits was studied with histology, 99mTc-MDP scintimetry and measurements of total calcium content. Bone was formed in the conduit by endochondral formation starting at both ends and continuing until fusion in the middle. After 2 weeks the bone had not yet met in the middle where fibrous tissue was seen. In eight animals 3H-proline was applied via one of the chambers, with the contralateral chamber as a saline-treated control. The collagen of the harvested tissue from the 3H-proline treated side had a 3H-hydroxyproline content 1000 times greater than had the control side. The 'drug test chamber' makes possible the study of local effects of drugs on healing of mature bone in vivo.
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  • Aspenberg, P., et al. (författare)
  • Failure of bone induction by bone matrix in adult monkeys
  • 1988
  • Ingår i: Journal of Bone and Joint Surgery: British Volume. - 0301-620X. ; 70:4, s. 625-627
  • Tidskriftsartikel (refereegranskat)abstract
    • Extraskeletal bone formation can be induced in rodents by implantation of demineralised bone matrix and such implantation has been used to treat bone defects in man, but it is uncertain if induction or merely conduction occurs. We studied bone induction in primates by excising segments of the fibulae of adult squirrel monkeys, defatting and demineralising them before reimplanting them into the quadriceps of the same animal. As a control experiment, rat matrix was prepared in exactly the same way and implanted in rats. After six weeks the implants were harvested and either ashed and analysed for calcium content or prepared for histology. In the rats, the calcium content indicated that about 20% of the original matrix had been replaced by new bone. In the monkeys the calcium content was about the same as that in normal body fluid and no bone was seen in histological sections. This result casts doubt on the use of demineralised human bone matrix as a bone inductor, although it may function by other mechanisms.
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19.
  • Aspenberg, Per, et al. (författare)
  • Fibroblast growth factor stimulates bone formation bone induction studied in rats
  • 1989
  • Ingår i: Acta Orthopaedica. - : Medical Journals Sweden AB. - 1745-3674 .- 0001-6470. ; 60:4, s. 473-476
  • Tidskriftsartikel (refereegranskat)abstract
    • Implantation of demineralized bone matrix in rodents elicits a series of cellular events leading to the formation of new bone inside and adjacent to the implant. This process is believed to be initiated by an inductive protein present in bone matrix. It has been suggested that local growth factors may further regulate the process once it has been initiated. This investigation was designed to study the effect of adding a growth factor to the inductive implant. Pairs of demineralized rat femoral diaphyses were implanted intramuscularly in rats. the marrow canal of one implant in each pair was filled with a carboxymethyl cellulose gel containing 75 ng of recombinant human basic fibroblast growth factor (FGF). the other implant in each pair served as a control. It was either filled with the gel without FGF or left untreated. Bone formation was induced by all the implants after 3 weeks. the amount of mineralized tissue in the FGF-treated implants was 25 percent greater than in untreated controls. the carboxymethyl cellulose gel alone did not affect the bone yield.
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20.
  • Aspenberg, P., et al. (författare)
  • Monkey bone matrix induces bone formation in the athymic rat, but not in adult monkeys
  • 1991
  • Ingår i: Journal of Orthopaedic Research. - : Wiley. - 0736-0266 .- 1554-527X. ; 9:1, s. 20-25
  • Tidskriftsartikel (refereegranskat)abstract
    • Demineralized bone matrix from young and adult monkeys was implanted intramuscularly for 6 weeks in athymic rats and adult monkeys. Cartilage and bone induction was evaluated by histology and calcium content. In the athymic rat, most implants induced cartilage or bone. In the monkeys, cartilage was formed only on rare occasions and there was no sign of bone formation. We conclude that (a) adult monkey bone matrix contains bone inductive properties; (b) these properties are not sufficient to induce bone formation in adult monkey muscle sites.
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21.
  • Aspenberg, Per, et al. (författare)
  • Rabbit bone matrix induces bone formation in the athymic rat
  • 1988
  • Ingår i: Acta Orthopaedica. - : Medical Journals Sweden AB. - 1745-3674 .- 0001-6470. ; 59:3, s. 276-278
  • Tidskriftsartikel (refereegranskat)abstract
    • Rabbit and rat bone matrix were implanted in athymic rat muscle, and the bone yield was measured as total calcium content after 4, 6, and 8 weeks. Matrix from both species induced equal amounts of new bone in the athymic rat. In rabbit and normal rat, the xenogenic matrix induced little or no bone formation. Thus, in the case of rabbit and rat, bone induction is species specific due to immunogenic mechanisms. the athymic rat can be used to measure inductive properties of bone matrix from different species.
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22.
  • Aune, Arne Kristian, et al. (författare)
  • Behandling av kneleddsartrose
  • 1998
  • Ingår i: Tidsskrift for Den Norske Lægeforening. - 0029-2001. ; 118:24, s. 3785-3790
  • Tidskriftsartikel (refereegranskat)abstract
    • Osteoarthritis of the knee is not a well defined illness, but is a result of different causes that may lead to joint failure due to chondral damage, synovial inflammation, subchondral bone formation, and the formation of osteophytes along the joint lines. The pathogenesis is unclear. We still lack treatment to cure the early prosess of chondral degeneration. The treatment of choice in early and moderate osteoarthritis of the knee is limited to counselling, physiotherapy, analgesics, and surgical correction of malalignment. Documentation is still lacking on chondral debridement and transplantation of the degenerated cartilage by cultured chondocytes, periosteum or perichondrium. An effective and well documented treatment of end-stage osteoarthritis of the knee in the older population is replacement of the joint by a knee prosthesis.
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24.
  • Battista, Simone, et al. (författare)
  • Sex and age differences in the patient-reported outcome measures and adherence to an osteoarthritis digital self-management intervention
  • 2024
  • Ingår i: Osteoarthritis and Cartilage Open. - 2665-9131. ; 6:1
  • Tidskriftsartikel (refereegranskat)abstract
    • ObjectiveTo explore sex and age differences in Patient-Reported Outcomes Measures (PROMs) and adherence to digital osteoarthritis (OA) self-management intervention.MethodsA register-based study with data from an OA digital self-management intervention. PROMs and adherence were collected at baseline and/or 3 ​month follow-up: ‘pain intensity’ in hip/knee (best/worst: 0–10), ‘activity impairments' (best/worst: 0–10), ‘overall health’ perception (worst/best: 0–10), ‘physical function’ (30-s chair stand test), ‘health-related quality of life’ (EQ-5D-5L index score; worst/best: 0.243–0.976), the subscales and total scores of the Knee Injury/Hip Disability and Osteoarthritis Outcome Score (KOOS/HOOS-12; worst/best: 0–100), ‘fear of movement’ (yes/no), ‘walking difficulties' (yes/no), ‘programme adherence’ (0–100 ​% and ≥80 ​% [yes/no]), ‘patient acceptable symptom state’ (PASS; yes/no), and ‘treatment failure’ (those who answered no to PASS question and thought the treatment failed [yes/no]). We used linear/logistic regression to calculate mean/risk differences in the PROMs and adherence levels among sex and age groups at 3-month follow-up. We employed entropy balancing to explore the contributions of baseline characteristics and different covariates to the sex/age differences.ResultsWe included 14,610 participants (mean (SD) age: 64.1 (9.1), 75.5 ​% females). Females generally reported better outcomes than males. Participants aged ≥70 had greater activity impairments, lower KOOS/HOOS-pain/function scores, more walking difficulties, less fear of movement and higher adherence than those <70. However, these differences were small and not likely clinically relevant.ConclusionNo clinically relevant differences in PROMs and adherence were found among sex/age groups in this digital OA programme, suggesting that sex/age seemed not to impact the outcomes of this intervention.
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25.
  • Beard, David J., et al. (författare)
  • Considerations and methods for placebo controls in surgical trials (ASPIRE guidelines)
  • 2020
  • Ingår i: The Lancet. - 0140-6736. ; 395:10226, s. 828-838
  • Forskningsöversikt (refereegranskat)abstract
    • Placebo comparisons are increasingly being considered for randomised trials assessing the efficacy of surgical interventions. The aim of this Review is to provide a summary of knowledge on placebo controls in surgical trials. A placebo control is a complex type of comparison group in the surgical setting and, although powerful, presents many challenges. This Review outlines what a placebo control entails and present understanding of this tool in the context of surgery. We consider when placebo controls in surgery are acceptable (and when they are desirable) in terms of ethical 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 done and interpreted. Use of placebo controls is justified in randomised controlled trials of surgical interventions provided there is a strong scientific and ethical 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 high risk of bias, particularly because of the placebo effect. Feasibility work is recommended to optimise the design and implementation of randomised controlled trials. This Review forms an outline for best practice and provides guidance, in the form of the Applying Surgical Placebo in Randomised Evaluations (known as ASPIRE) checklist, for those considering the use of a placebo control in a surgical randomised controlled trial.
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26.
  • 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.
  •  
27.
  • Bergenudd, H, et al. (författare)
  • The articular cartilage after osteotomy for medial gonarthrosis. Biopsies after 2 years in 19 cases
  • 1992
  • Ingår i: Acta Orthopaedica Scandinavica. - 0001-6470. ; 63:4, s. 413-416
  • Tidskriftsartikel (refereegranskat)abstract
    • In 19 consecutive patients with medial gonarthrosis, an arthroscopic examination with a biopsy of the load-bearing cartilage in the medial femoral condyle was undertaken at the same time as a proximal tibial osteotomy. A follow-up arthroscopic biopsy was performed on an average of 2 years after the osteotomy. In 9 knees there was an improvement in the cartilage quality, 8 knees were unchanged, whereas 2 knees had deteriorated. Radiographically, 6 knees had improved, 11 were unchanged and 2 had deteriorated. We found no correlation between cartilage improvement and the clinical and radiographic outcome. Our results confirm that an osteotomy has a beneficial effect on the load-bearing cartilage in the medial femoral condyle.
  •  
28.
  • Beynnon, Bruce D, et al. (författare)
  • Are validated questionnaires valid?
  • 2006
  • Ingår i: Journal of Bone and Joint Surgery. American Volume. - 0021-9355. ; 88:2, s. 448-448
  • Tidskriftsartikel (refereegranskat)
  •  
29.
  •  
30.
  •  
31.
  • Bond, M., et al. (författare)
  • Responsiveness of the OARSI-OMERACT osteoarthritis pain and function measures
  • 2012
  • Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 20:6, s. 541-547
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To assess the responsiveness of the Intermittent and Constant Osteoarthritis Pain (ICOAP) measure, Hip Disability and Osteoarthritis Outcome Score Physical Function Short Form (HOOS-PS), and the Knee Disability and Osteoarthritis Outcome Score Physical Function Short Form (KOOS-PS) in a pharmacological trial. Methods: Data were obtained from a randomized double-blind trial comparing naproxcinod with naproxen and ibuprofen in individuals with hip or knee osteoarthritis (OA) (NCT00662896). Participants completed the ICOAP, HOOS-PS/KOOS-PS, and Western Ontario and McMaster Universities OA Index (WOMAC) Likert version 3.0 before and 13 weeks after treatment. In hip and knee OA participants separately, the mean pre-post treatment change in scores, effect size (ES) and standardized response mean (SRM) were determined for each measure by treatment arm, and for all arms combined. Results: Of 349 trial participants, 156 with knee OA and 48 with hip OA completed all measures at both time-points and were included (mean age 61 years; two-thirds female). Although there was both within treatment and between treatment variability in response, among knee OA participants, ICOAP intermittent, constant, and total scores and KOOS-PS scores showed, on average, moderate effects, with ESs ranging from 0.46 to 0.54 and SRMs from 0.49 to 0.56. Similar changes were seen for the WOMAC pain and function subscales (0.58 and 0.58, respectively). In those with hip OA, no significant improvement in symptoms was seen for any measure. Conclusion: Responsiveness to pharmaceutical intervention was demonstrated for ICOAP and KOOS-PS among participants with knee OA. Absence of treatment response precluded assessment of responsiveness in hip OA. (C) 2012 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
  •  
32.
  • Bunzli, Samantha, et al. (författare)
  • Placebo Surgery Controlled Trials : Do They Achieve What They Set Out To Do? A Systematic Review
  • 2021
  • Ingår i: Annals of Surgery. - 1528-1140. ; 273:6, s. 1102-1107
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: To explore whether placebo surgery controlled trials achieve what they set out to do by investigating discrepancy between projected and actual design aspects of trials identified through systematic review methods. SUMMARY BACKGROUND: Interest in placebo surgery controlled trials is growing in response to concerns regarding unnecessary surgery and the societal cost of low-value healthcare. As questions about the justifiability of using placebo controls in surgery have been addressed, attention is now being paid to more practical concerns. METHODS: Six databases were searched from inception - May 2020 (MEDLINE, Embase, Emcare, APA PsycInfo, CINAHL, Cochrane Library). Placebo surgery controlled trials with a published protocol were included. Three authors extracted "projected" design aspects from protocols and "actual" design aspects from main findings papers. Absolute and relative difference between projected and actual design aspects were presented for each trial. Trials were grouped according to whether they met their target sample size ("completed") and were concluded in a timely fashion. Pairs of authors assessed risk of bias. RESULTS: Of 24 trials with data available to analyse; 3 were completed and concluded within target timeframe; 10 were completed and concluded outside the target timeline; 4 were completed without clear target timeframes; 2 were incomplete and concluded within the target framework; 5 were incomplete and concluded outside the target timeline. Trials which reached the recruitment target underestimated trial duration by 88% and number of recruitment sites by 87%. CONCLUSIONS: Trialists need to factor additional time and sites into future placebo surgery controlled trials. A robust reporting framework of projected and actual trial design is imperative for trialists to learn from their predecessors. REVIEW REGISTRATION: PROSPERO (CRD42019133296).
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33.
  • Burmester, Gerd, et al. (författare)
  • The appropriate use of non-steroidal anti-inflammatory drugs in rheumatic disease: opinions of a multidisciplinary European expert panel
  • 2011
  • Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 70:5, s. 818-822
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction Given the safety issues of nonsteroidal anti-inflammatory drugs (NSAID) and the robustness of guidelines, making treatment choices in daily clinical practice is increasingly difficult. This study aimed systematically to analyse the opinions of a multidisciplinary European expert panel on the appropriateness of different NSAID, with or without the use of a proton pump inhibitor (PPI), in individual patients with chronic rheumatic disease. Methods Using the Research and Development/University of California at Los Angeles appropriateness method, the appropriateness of five (non-)selective NSAID with or without a PPI was assessed for 144 hypothetical patient profiles, ie, unique combinations of cardiovascular and gastrointestinal risk factors. Appropriateness statements were calculated for all indications. Results All options without PPI were considered appropriate in patients with no gastrointestinal/cardiovascular risk factors. Cyclooxygenase-2 selective inhibitors (C2SI) alone and non-selective NSAID plus PPI were preferred for patients with elevated gastrointestinal risk and low cardiovascular risk. Naproxen plus PPI was favoured in patients with high cardiovascular risk. For the combination of high gastrointestinal/high cardiovascular risk the use of any NSAID was discouraged; if needed, naproxen plus PPI or a C2SI plus PPI could be considered. Discussion The panel results may support treatment considerations at the level of individual patients, according to their gastrointestinal/cardiovascular risk profile.
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34.
  •  
35.
  • Chard, Jiri, et al. (författare)
  • Osteoarthritis
  • 2002
  • Ingår i: Clinical evidence. - 1462-3846. ; 14:5, s. 571-572
  • Tidskriftsartikel (refereegranskat)
  •  
36.
  • 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.
  •  
37.
  • 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.
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38.
  • Christensen, Robin, et al. (författare)
  • Effect of Weight Maintenance on Symptoms of Knee Osteoarthritis in Obese Patients: A Twelve-Month Randomized Controlled Trial 1
  • 2015
  • Ingår i: Arthritis Care and Research. - : Wiley. - 2151-4658 .- 2151-464X. ; 67:5, s. 640-650
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective. To compare results of obese patients with knee osteoarthritis (OA) who, after an intensive weight loss regimen, received 1 year of either dietary support (D), a knee-exercise program (E), or "no attention" (C; control group). Methods. We conducted a randomized, 2-phase, parallel-group trial. A total of 192 obese participants with knee OA were enrolled; the mean age was 62.5 years and 81% were women with a mean entry weight of 103.2 kg. In phase 1, all participants were randomly assigned to 1 of 3 groups and began a dietary regimen of 400-810 and 1,250 kcal/day for 16 weeks (2 8-week phases) to achieve a major weight loss. Phase 2 consisted of 52 weeks' maintenance in either group D, E, or C. Outcomes were changes from randomization in pain on a 100-mm visual analog scale, weight, and response according to the Outcome Measures in Rheumatology-Osteoarthritis Research Society International criteria. Results. Mean weight loss for phase 1 was 12.8 kg. After 1 year on maintenance therapy, the D group sustained a lower weight (11.0 kg, 95% confidence interval [95% CI] 9.0, 12.8 kg) than those in the E (6.2, 95% CI 4.4, 8.1 kg) and C (8.2, 95% CI 6.4, 10.1 kg) groups (P = 0.002 by analysis of covariance [ANCOVA]). Adherence was low in the E group. All groups had statistically significant pain reduction (D: 6.1; E: 5.6; and C: 5.5 mm) with no difference between groups (P = 0.98 by ANCOVA). In each group 32 (50%), 26 (41%), and 33 (52%) participants responded to treatment in the D, E, and C groups, respectively, with no statistically significant difference in the number of responders (P = 0.41). Conclusion. A significant weight reduction with a 1-year maintenance program improves knee OA symptoms irrespective of maintenance program.
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39.
  • Christensen, Robin, et al. (författare)
  • Weight loss for overweight patients with knee or hip osteoarthritis
  • 2017
  • Ingår i: Cochrane Database of Systematic Reviews. - 1361-6137. ; 2017:11
  • Tidskriftsartikel (refereegranskat)abstract
    • This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To determine the benefits and harms associated with weight loss in overweight individuals with knee or hip osteoarthritis in terms of pain, physical function, quality of life, and safety. Further we will have an explicit focus on quality of the weight loss intervention (including magnitude and intensity) (Herbert 2005), to see whether there is a dose-response relationship at the trial (i.e. group) level.
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40.
  • Clohisy, John C., et al. (författare)
  • Clinical trials in orthopaedics and the future direction of clinical investigations for femoroacetabular impingement
  • 2013
  • Ingår i: ; , s. 47-52
  • Konferensbidrag (refereegranskat)abstract
    • Femoroacetabular impingement (FAI) represents a heterogeneous group of disorders that affect a diverse patient population. The natural history of the disease, the role of nonsurgical management, the indications for surgery, optimal surgical techniques, and the predictors of treatment outcomes need to be further defined. To date, clinical research reports have included primarily surgical case series. Future clinical investigations are needed to establish improved clinical evidence to guide patient care. Most urgent is the need to better understand the potential role of standardized nonsurgical treatment options for FAI and to define the predictors of surgical and nonsurgical outcomes. Future randomized controlled trials and large observational cohort studies targeted at these clinical research deficiencies will strengthen the evidence and improve informed decision making regarding the management of symptomatic FAI.
  •  
41.
  • 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.
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42.
  • Cronström, Anna, et al. (författare)
  • Interpretation threshold values for patient-reported outcomes in patients participating in a digitally delivered first-line treatment program for hip or knee osteoarthritis
  • 2023
  • Ingår i: Osteoarthritis and Cartilage Open. - : Elsevier. - 2665-9131. ; 5:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Establish proportions of patients reporting important improvement, acceptable symptoms and treatment failure and define interpretation threshold values for pain, patient-reported function and quality-of-life after participating in digital first-line treatment including education and exercise for hip and knee osteoarthritis (OA).Methods: Observational study. Responses to the pain Numeric Rating Scale (NRS, 0-10 best to worst), Knee injury and Osteoarthritis Outcome Score 12 (KOOS-12) and Hip disability and Osteoarthritis Outcome Score 12 (HOOS-12, both 0-100 worst to best) were obtained for 4383 (2987) and 20341 (1264) participants with knee (hip) OA at 3 and 12 months post intervention.. Threshold values for Minimal Important Change (MIC), Patient Acceptable Symptom State (PASS) and Treatment Failure (TF) were estimated using anchor-based predictive modeling.Results: 70–85% reported an important improvement in pain, function and quality of life after 3 and 12 months follow-up. 42% (3 months) and 51% (12 months) considered their current state as satisfactory, whereas 2-4% considered treatment failed. MIC values were -1 (NRS) and 0-4 (KOOS/HOOS-12) across follow-ups and joint affected. PASS threshold value for NRS was 3, and 53–73 for the KOOS/HOOS-12 subscales Corresponding values for TF were 5 (NRS) and 34–55 (KOOS/HOOS-12). Patients with more severe pain at baseline had higher MIC scores and accepted poorer outcomes at follow-ups.Conclusion: Threshold estimates aid in the interpretation of outcomes after first-line OA interventions assessed with NRS Pain and KOOS/HOOS-12. Baseline pain severity is important to consider when interpreting threshold values after first-line interventions in these patients.
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43.
  • Culvenor, Adam G., et al. (författare)
  • Loss of patellofemoral cartilage thickness over 5 years following ACL injury depends on the initial treatment strategy : Results from the KANON trial
  • 2019
  • Ingår i: British journal of sports medicine. - : BMJ. - 0306-3674 .- 1473-0480. ; 53:18, s. 1168-1173
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: To evaluate changes in patellofemoral cartilage thickness over 5 years after anterior cruciate ligament (ACL) injury and to determine the impact of treatment strategy. Methods: 121 adults (ages 18-35 years, 26% women) had an ACL injury and participated in the KANON randomised controlled trial. Of those, 117 had available MRIs at baseline (<4 weeks post-ACL rupture) and at least one follow-up measurement (2, 5 years). Patellofemoral cartilage thickness was analysed by manual segmentation (blinded to acquisition order). Patellar, trochlear and total patellofemoral cartilage thickness changes were compared between as-randomised (rehabilitation+early ACL reconstruction (ACLR) (n=59) vs rehabilitation+optional delayed ACLR (n=58)) and as-treated groups (rehabilitation+early ACLR (n=59) vs rehabilitation +delayed ACLR (n=29) vs rehabilitation alone (n=29)). Results: Patellofemoral cartilage thickness decreased-58 μm (95% CI-104 to-11 μm) over 5 years post-ACL rupture, with the greatest loss observed in trochlea during the first 2 years. Participants randomised to rehabilitation+early ACLR had significantly greater loss of patellar cartilage thickness compared with participants randomised to rehabilitation+optional delayed ACLR over the first 2 years (-25 μm (-52, 1 μm) vs +14 μm (-6 to 34 μm), p=0.02) as well as over 5 years (-36 μm (-78 to 5 μm) vs +18 μm (-7, 42 μm), p=0.02). There were no statistically significant differences in patellofemoral cartilage thickness changes between as-treated groups. Conclusion: Patellofemoral (particularly trochlear) cartilage thickness loss was observed in young adults following acute ACL rupture. Early ACLR was associated with greater patellofemoral (particularly patellar) cartilage thickness loss over 5 years compared with optional delayed ACLR, indicating that early surgical intervention may be associated with greater short-term structural patellofemoral cartilage deterioration compared with optional delayed surgery. Trial registration number: ISRCTN84752559; Post-results.
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44.
  • Dahlberg, Leif E., et al. (författare)
  • Improving osteoarthritis care by digital means - Effects of a digital self-management program after 24- or 48-weeks of treatment
  • 2020
  • Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 15:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Osteoarthritis (OA) is highly prevalent in older adults and a growing cause of disability. Easily accessible first-line treatment of OA is increasingly important. Digital self-management programs have in recent years become available. Evidence of short-term effects of such programs are abundant, yet reports on long-term benefits and adherence to treatment are scarce. The current study’s objective was to investigate the long-term pain and function outcomes of people with hip or knee OA participating in a digital self-management programme. Methods and findings In this longitudinal cohort study, individuals with hip and knee OA, from the register of a digital self-management program and with 0-24-week (n = 499) or 0-48-week adherence (n = 138), were included. The treatment effect in terms of monthly pain (NRS, 0–10 worst to best) and physical function (30-second chair stand test (30CST), number of repetitions) change were investigated using a mixed model, controlling for the effect of age, body mass index (BMI), gender and index joint. For the 24-week sub-sample, pain NRS decreased monthly by -0.43 units (95% CI -0.51, -0.35, mean knee pain from 5.6 to 3.1, and hip pain from 5.9 to 3.8) and 30CST repetitions increased monthly by 0.76 repetitions (95% CI 0.64, 0.89 mean for knee from 10.0 to 14.3, and for hip from 10.9 to 14.8). For the 48-week sub-sample, pain decreased monthly by -0.39 units (95% CI -0.43, -0.36, mean knee pain from 5.7 to 3.2, and hip pain from 5.8 to 3.8), and repetitions increased by 0.72 repetitions (95% CI 0.65, 0.79, mean repetitions for knee from 10.3 to 14.4, and for hip from 11.1 to 14.9). There were no clinically relevant effects on the improvement of pain or function by any covariate (age, sex, index joint). The lack of a control group and randomization limit our ability to explain the mechanisms of the observed results. Conclusions Continuously participating in a digital OA treatment program for 6 or 12 months was associated with a clinically important decrease in joint pain and increased physical function, in hip and knee OA. Future research should follow OA-related outcomes in participants that end their treatment to explore when and why that decision was made.
  •  
45.
  • Dahlberg, Leif, et al. (författare)
  • Proteoglycan fragments in joint fluid : Influence of arthrosis and inflammation
  • 1992
  • Ingår i: Acta Orthopaedica. - : Medical Journals Sweden AB. - 1745-3674 .- 0001-6470. ; 63:4, s. 417-423
  • Tidskriftsartikel (refereegranskat)abstract
    • We determined the concentration of proteoglycan fragments in knee joint fluid collected from knee-ligament injured patients more than 6 months after the trauma and from patients with acute pyrophosphate arthritis and arthrosis or with arthrosis only. Injured patients with normal or only mildly altered cartilage at arthroscopy and with normal radiographs, had twice the average concentration of healthy volunteers. Other injured patients with advanced, radiographic signs of arthrosis, had synovial fluid proteoglycan fragment concentrations within the range of healthy volunteers. Patients with pyrophosphate arthritis had the highest concentrations, substantially increased compared with both arthrosis patients, with or without knee injury and healthy volunteers. Likewise, there was an inverse relation between the degree of arthrosis and the concentration of proteoglycan fragments in the joint fluid in patients with pyrophosphate arthritis and arthrosis or with arthrosis only. We conclude that synovial fluid levels of proteoglycan fragments are influenced by the mass of cartilage matrix remaining in the joint, the inflammatory activity in the joint, and the metabolic activity of the cartilage cells.
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46.
  •  
47.
  • Davis, A. M., et al. (författare)
  • Comparative, validity and responsiveness of the HOOS-PS and KOOS-PS to the WOMAC physical function subscale in total joint replacement for Osteoarthritis
  • 2009
  • Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 17:7, s. 843-847
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To evaluate the internal consistency of the Hip disability and Osteoarthritis Outcome Score-Physical Function Short-form (HOOS-PS) and the Knee injury and Ostecarthritis Outcome Score-Physical Function Short-form (KOOS-PS) in total hip replacement (THR) and total knee (TKR) replacement. Construct validity and responsiveness were compared to the Western Ontario McMaster Universities' Osteoarthritis Index (WOMAC) Likert 3.0 physical function (PF) subscale and the PF excluding the items in the short measures (PF-exclusions). Methods: Participants completed the full HOOS or KOOS, measures of fatigue, anxiety. depression and the Chronic Pain Grade (CPG) pre-surgery and the HOOS or KOOS 6 months post-surgery. Internal consistency for the HOOS-PS and KOOS-PS was calculated using Cronbach's alpha. For construct validity, it was hypothesized that correlations between the HOOS-PS or KOOS-PS and PF and PF-exclusions with fatigue, CPG, anxiety and depression and HOOS/KOOS pain scales would differ by magnitudes of <0.1. Standardized response means (SRMs) were calculated for the HOOS-PS, KOOS-PS, PF and PF-exclusions and hypothesized to be >1. Results: The THR group (n = 201) had a mean age of 62.3 years; 53.2% were female. The TKR group (n = 248) had a mean age of 64.5 years; 63.7% were female. Cronbach's alpha was 0.79 and 0.89 for the HOOS-PS and KOOS-PS, respectively, confirming that the measures represented a homogeneous construct. The correlation of the HOOS-PS to the PF and PF-exclusions was 0.90 and 0.86, respectively; r = 0.90 (PF) and r = 0.85 (PF-exclusions) for the KOOS-PS. The results supported the construct validity hypotheses. For THR, the SRM was 1.5, 1.7 and 1.7 for the HOOS-PS, PF and PF-exclusions; for TKR, the SRM was 1.4, 1.5 and 1.7, respectively. Conclusions: The short HOOS-PS and KOOS-PS represent homogenous short measures of PF with similar construct validity and responsiveness to the 17-item PF. The HOOS-PS and KOOS-PS are parsimonious, valid and responsive for evaluating PF in THR and TKR. (C) 2009 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
  •  
48.
  • Davis, A. M., et al. (författare)
  • Evaluating the responsiveness of the ICOAP following hip or knee replacement
  • 2010
  • Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 18:8, s. 1043-1045
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: The Intermittent and Constant Osteoarthritis (OA) Pain (ICOAP) questionnaire evaluates the constructs of 'intermittent' and 'constant' pain. Theses are conceptually different from 'pain on activity' and pain 'intensity' as measured by the WOMAC and Chronic Pain Grade (CPG), measures commonly used in OA. The purpose of this study was to evaluate the responsiveness of the ICOAP, and different pain constructs in primary total hip (THR) and total knee (TKR) replacement. Methods: Patients completed the ICOAP, WOMAC and HOOS/KOOS pain and the CPG pre- and 6 months post surgery. Scores were standardized to 0 to 100, where higher scores indicate worse pain. Descriptive statistics were calculated for all data. The standardized response mean (SRM) was calculated for each measure as were correlations of change scores. Results: The THR group (n = 34) ranged in age from 37-85 years with 74% male. The TKR group (n = 44) ranged in age from 45-86 years with 75% female. Both groups had significant improvement (p < .0001) on all pain measures but the TKR group had smaller improvements. For THR, the SMR was 1.50, 2.31 and 2.29 for constant, intermittent and total scores and for TKR, was 0.84, 1.02 and 1.02 respectively. The SMR ranged from 2.05 to 2.99 for the other measures for THR and from 1.13 to 1.44 for TKR patients. Correlations of the change scores were ranged from 0.26 to 0.81. Conclusion: Multi-faceted constructs of pain are effectively relieved through joint replacement and all measures including the ICOAP demonstrated responsiveness. (C) 2010 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
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49.
  •  
50.
  • Davis, A M, et al. (författare)
  • The development of a short measure of physical function for hip OA HOOS-Physical Function Shortform (HOOS-PS): an OARSI/OMERACT initiative
  • 2008
  • Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 16:5, s. 551-559
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To derive a cross-culturally valid, short measure of physical function using function subscales (daily living and sports and recreation) of the Hip disability and Osteoarthritis Outcome Score (HOOS). Methods: Rasch analysis was conducted on data from individuals from multiple countries who had hip osteoarthritis (OA). Fit of the data to the Rasch model was evaluated by model chi(2) and item fit statistics (chi(2), size of residual, and F-test). Differential item functioning was evaluated by gender, age and country. Unidimensionality was evaluated by factor analysis of residuals. Individual data sets were analyzed and data pooled and re-analyzed for fit to the model. Regression modeling was conducted to derive a nomogram converting raw summed scores to Rasch derived interval scores. Results: Seven data sets were included (n = 2991), ages 19-96 years, male/female ratio was 1:1.23. The final model included five HOOS items. From the easiest to most difficult, the items (logit) were as follows: sitting (1.832), descending stairs (0.729), getting in/out of bath or shower (0.255), twisting/pivoting on loaded leg (-0.221) and running (-2.595). The separation index was 0.80. Conclusion: The daily activity and sports and recreational items of the HOOS were reduced to five items achieving a feasible, short measure of physical function with interval level properties. This tool has potential for use as the function component of an OA severity scoring system. Further testing of this measure is warranted.
  •  
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