Clusters of biochemical markers are associated with radiographic subtypes of osteoarthritis (OA) in subject with familial OA at multiple sites. The GARP study

SummaryObjectiveTo assess the relationship of biochemical markers and radiographic signs of osteoarthritis (ROA) in the subjects with symptomatic osteoarthritis (OA) at multiple sites of the Genetics osteoARthritis and Progression (GARP) study.MethodsWe have measured eight biochemical markers, representing tissue turnover of cartilage, bone, synovium, and inflammation. ROA was assessed in the knees, hips, hands, vertebral facet joints and spinal disc degeneration (DD) by using the Kellgren score. A proportionate score was subsequently made for each joint location based on the number of joints with ROA. Principal component and linear mixed model analyses were applied to analyze the data.ResultsThree different clusters of markers were identified that may reflect different pathophysiological processes of OA. The first component appeared to be reflected by structural markers of cartilage and bone turnover and associated especially in subjects with hip ROA. The second component was reflected by a marker of inflammation and was associated with knee ROA, high Western Ontario and McMaster Universities (WOMAC) scores and body mass index (BMI). The third component included markers of cartilage turnover and was associated with ROA at hands, spine as well as age. High familial aggregation was observed for serum cartilage oligomeric matrix protein (S-COMP) (70%) and serum N-propeptide of collagen type IIA (S-PIIANP) (62%).ConclusionUsing a large well-characterized study and eight biochemical markers, we were able to observe three components that may reflect different molecular mechanisms (bone, cartilage, synovium turnover and inflammation). Our data suggested that these components contribute differently to ROA at different joint sites

Association between Several Clinical and Radiological Determinants with Long-Term Clinical Progression and Good Prognosis of Lower Limb Osteoarthritis

OBJECTIVE: To investigate the factors associated with clinical progression and good prognosis in patients with lower limb osteoarthritis (OA). METHODS: Cohort study of 145 patients with OA in either knee, hip or both. Progression was defined as 1) new joint prosthesis or 2) increase in WOMAC pain or function score during 6-years follow-up above pre-defined thresholds. Patients without progression with decrease in WOMAC pain or function score lower than pre-defined thresholds were categorized as good prognosis. Relative risks (RRs) for progression and good prognosis with 95% confidence interval (95% CI) were calculated by comparing the highest tertile or category to the lowest tertile, for baseline determinants (age, sex, BMI, WOMAC pain and function scores, pain on physical examination, total range of motion (tROM), osteophytes and joint space narrowing (JSN) scores), and for worsening in WOMAC pain and function score in 1-year. Adjustments were performed for age, sex, and BMI. RESULTS: Follow-up was completed by 117 patients (81%, median age 60 years, 84% female); 62 (53%) and 31 patients (26%) showed progression and good prognosis, respectively. These following determinants were associated with progression: pain on physical examination (RR 1.2 (1.0 to 1.5)); tROM (1.4 (1.1 to 1.6); worsening in WOMAC pain (1.9 (1.2 to 2.3)); worsening in WOMAC function (2.4 (1.7 to 2.6)); osteophytes 1.5 (1.0 to 1.8); and JSN scores (2.3 (1.5 to 2.7)). Worsening in WOMAC pain (0.1 (0.1 to 0.8)) and function score (0.1 (0.1 to 0.7)), were negatively associated with good prognosis. CONCLUSION: Worsening of self-reported pain and function in one year, limited tROM and higher osteophytes and JSN scores were associated with clinical progression. Worsening in WOMAC pain and function score in 1- year were associated with lower risk to have good prognosis. These findings help to inform patients with regard to their OA prognosis

EULAR recommendations for the use of imaging in the clinical management of peripheral joint osteoarthritis

The increased information provided by modern imaging has led to its more extensive use. Our aim was to develop evidence-based recommendations for the use of imaging in the clinical management of the most common arthropathy, osteoarthritis (OA). A task force (including rheumatologists, radiologists, methodologists, primary care doctors and patients) from nine countries defined 10 questions on the role of imaging in OA to support a systematic literature review (SLR). Joints of interest were the knee, hip, hand and foot; imaging modalities included conventional radiography (CR), MRI, ultrasonography, CT and nuclear medicine. PubMed and EMBASE were searched. The evidence was presented to the task force who subsequently developed the recommendations. The strength of agreement for each recommendation was assessed. 17 011 references were identified from which 390 studies were included in the SLR. Seven recommendations were produced, covering the lack of need for diagnostic imaging in patients with typical symptoms; the role of imaging in differential diagnosis; the lack of benefit in monitoring when no therapeutic modification is related, though consideration is required when unexpected clinical deterioration occurs; CR as the first-choice imaging modality; consideration of how to correctly acquire images and the role of imaging in guiding local injections. Recommendations for future research were also developed based on gaps in evidence, such as the use of imaging in identifying therapeutic targets, and demonstrating the added value of imaging. These evidence-based recommendations and related research agenda provide the basis for sensible use of imaging in routine clinical assessment of people with OA

Reference curves for the Australian/Canadian Hand Osteoarthritis Index in the middle-aged Dutch population

Objective. The aim was to establish reference curves of the Australian/Canadian Hand Osteoarthritis Index (AUSCAN), a widely used questionnaire assessing hand complaints. Methods. Analyses were performed in a population-based sample, The Netherlands Epidemiology of Obesity study (n = 6671, aged 45–65 years). Factors associated with AUSCAN scores were analysed with ordered logistic regression, because AUSCAN data were zero inflated, dividing AUSCAN into three categories (0 vs 1–5 vs >5). Age- and sex-specific reference curves for the AUSCAN (range 0–60; higher is worse) were developed using quantile regression in conjunction with fractional polynomials. Observed scores in relevant subgroups were compared with the reference curves. Results. The median age was 56 [interquartile range (IQR): 50–61] years; 56% were women and 12% had hand OA according to ACR criteria. AUSCAN scores were low (median 1; IQR: 0–4). Reference curves where higher for women, and increased moderately with age: 95% percentiles for AUSCAN in men and women were, respectively, 5.0 and 12.3 points for a 45-year-old, and 15.2 and 33.6 points for a 65-year-old individual. Additional associated factors included hand OA, inflammatory rheumatic diseases, FM, socio-economic status and BMI. Median AUSCAN pain subscale scores of women with hand OA lay between the 75th and 90th centiles of the general population. Conclusion. AUSCAN scores in the middle-aged Dutch population were low overall, and higher in women than in men. AUSCAN reference curves could serve as a benchmark in research and clinical practice settings. However, the AUSCAN does not measure hand complaints specific for hand OA

Comparing quality of life and postoperative pain after limited access and conventional aortic valve replacement: design and rationale of the LImited access aortic valve replacement (LIAR) trial

Background: Surgical aortic valve replacement (SAVR) via limited access approaches ('mini-AVR') have proven to be safe alternative for the surgical treatment of aortic valve disease. However, it remains unclear whether these less invasive approaches are associated with improved quality of life and/or reduced postoperative pain when compared to conventional SAVR via full median sternotomy (FMS).Study design: The LImited access Aortic valve Replacement (LIAR) trial is a single-center, single blind randomized controlled clinical trial comparing 2 arms of 80 patients undergoing limited access SAVR via J-shaped upper hemi-sternotomy (UHS) or conventional SAVR through FMS. In all randomized patients, the diseased native aortic valve is planned to be replaced with a rapid deployment stented bioprosthesis. Patients unwilling or unable to participate in the randomized trial will be treated conventionally via SAVR via FMS and with implantation of a sutured valve prosthesis. These patients will participate in a prospective registry.Study methods: Primary outcome is improvement in cardiac-specific quality of life, measured by two domains of the Kansas City Cardiomyopathy Questionnaire up to one year after surgery. Secondary outcomes include, but are not limited to: generic quality of life measured with the Short Form-36, postoperative pain, perioperative (technical success rate, operating time) and postoperative outcomes (30-day and one-year mortality), complication rate and hospital length of stay.Conclusion: The LIAR trial is designed to determine whether a limited access approach for SAVR ("mini-AVR") is associated with improved quality of life and/or reduced postoperative pain compared with conventional SAVR through FMS

EULAR recommendations for the use of imaging in the clinical management of peripheral joint osteoarthritis

The increased information provided by modern imaging has led to its more extensive use. Our aim was to develop evidence-based recommendations for the use of imaging in the clinical management of the most common arthropathy, osteoarthritis (OA). A task force (including rheumatologists, radiologists, methodologists, primary care doctors and patients) from nine countries defined 10 questions on the role of imaging in OA to support a systematic literature review (SLR). Joints of interest were the knee, hip, hand and foot; imaging modalities included conventional radiography (CR), MRI, ultrasonography, CT and nuclear medicine. PubMed and EMBASE were searched. The evidence was presented to the task force who subsequently developed the recommendations. The strength of agreement for each recommendation was assessed. 17â 011 references were identified from which 390 studies were included in the SLR. Seven recommendations were produced, covering the lack of need for diagnostic imaging in patients with typical symptoms; the role of imaging in differential diagnosis; the lack of benefit in monitoring when no therapeutic modification is related, though consideration is required when unexpected clinical deterioration occurs; CR as the first-choice imaging modality; consideration of how to correctly acquire images and the role of imaging in guiding local injections. Recommendations for future research were also developed based on gaps in evidence, such as the use of imaging in identifying therapeutic targets, and demonstrating the added value of imaging. These evidence-based recommendations and related research agenda provide the basis for sensible use of imaging in routine clinical assessment of people with OA

The Peculiar Nebula Simeis 57: I. Ionized Gas and Dust Extinction

We present high resolution radio continuum maps of the Galactic nebula Simeis 57 (= HS 191 = G 80.3+4.7) made with the WSRT and the DRAObservatory at frequencies of 609, 1412 and 1420 MHz. At optical and at radio wavelengths, the nebula has a peculiar ``S'' shape, crossed by long, thin and straight filaments. The radio maps, combined with other maps from existing databases, show essentially all radio emission from the peculiar and complex nebula to be thermal and optically thin. Although neither the distance nor the source of excitation of Simeis 57 are known, the nebula can only have a moderate electron density of typically n(e) = 100 cm-3. Its mass is also low, not exceeding some tens of solar masses. Peak emission measures are 5000 pc cm-6.Obscuring dust is closely associated with the nebula, but seems to occur mostly in front of it. Extinctions vary from A(V) = 1.0 mag to A(V) = 2.8 mag with a mean of about 2 mag. The extinction and the far-infrared emission at 100 microns are well-correlated.Comment: Accepted for Publication in Astronomy & Astrophysic

Radiographic scoring methods in hand osteoarthritis - a systematic literature search and descriptive review

OBJECTIVE\nThis systematic literature review aimed to evaluate the use of conventional radiography (CR) in hand osteoarthritis (OA) and to assess the metric properties of the different radiographic scoring methods.\nDESIGN\nMedical literature databases up to November 2013 were systematically reviewed for studies reporting on radiographic scoring of structural damage in hand OA. The use and metric properties of the scoring methods, including discrimination (reliability, sensitivity to change), feasibility and validity, were evaluated.\nRESULTS\nOf the 48 included studies, 10 provided data on reliability, 11 on sensitivity to change, four on feasibility and 36 on validity of radiographic scoring methods. Thirteen different scoring methods have been used in studies evaluating radiographic hand OA. The number of examined joints differed extensively and the obtained scores were analyzed in various ways. The reliability of the assessed radiographic scoring methods was good for all evaluated scoring methods, for both cross-sectional and longitudinal radiographic scoring. The responsiveness to change was similar for all evaluated scoring methods. There were no major differences in feasibility between the evaluated scoring methods, although the evidence was limited. There was limited knowledge about the validity of radiographic OA findings compared with clinical nodules and deformities, whereas there was better evidence for an association between radiographic findings and symptoms and hand function.\nCONCLUSIONS\nSeveral radiographic scoring methods are used in hand OA literature. To enhance comparability across studies in hand OA, consensus has to be reached on a preferred scoring method, the examined joints and the used presentation of data.Pathophysiology and treatment of rheumatic disease

Prima facie reasons to question enclosed intellectual property regimes and favor open-source regimes for germplasm

In principle, intellectual property protections (IPPs) promote and protect important but costly investment in research and development. However, the empirical reality of IPPs has often gone without critical evaluation, and the potential of alternative approaches to lend equal or greater support for useful innovation is rarely considered. In this paper, we review the mounting evidence that the global intellectual property regime (IPR) for germplasm has been neither necessary nor sufficient to generate socially beneficial improvements in crop plants and maintain agrobiodiversity. Instead, based on our analysis, the dominant global IPR appears to have contributed to consolidation in the seed industry while failing to genuinely engage with the potential of alternatives to support social goods such as food security, adaptability, and resilience. The dominant IPR also constrains collaborative and cumulative plant breeding processes that are built upon the work of countless farmers past and present. Given the likely limits of current IPR, we propose that social goods in agriculture may be better supported by alternative approaches, warranting a rapid move away from the dominant single-dimensional focus on encouraging innovation through ensuring monopoly profits to IPP holders

A genome-wide association study suggests that a locus within the ataxin 2 binding protein 1 gene is associated with hand osteoarthritis: the Treat-OA consortium

To identify the susceptibility gene in hand osteoarthritis (OA) the authors used a two-stage approach genome-wide association study using two discovery samples (the TwinsUK cohort and the Rotterdam discovery subset; a total of 1804 subjects) and four replication samples (the Chingford Study, the Chuvasha Skeletal Aging Study, the Rotterdam replication subset and the Genetics, Arthrosis, and Progression (GARP) Study; a total of 3266 people). Five single-nucleotide polymorphisms (SNPs) had a likelihood of association with hand OA in the discovery stage and one of them (rs716508), was successfully confirmed in the replication stage (meta-analysis p = 1.81×10−5). The C allele conferred a reduced risk of 33% to 41% using a case–control definition. The SNP is located in intron 1 of the A2BP1 gene. This study also found that the same allele of the SNP significantly reduced bone density at both the hip and spine (p<0.01), suggesting the potential mechanism of the gene in hand OA might be via effects on subchondral bone. The authors' findings provide a potential new insight into genetic mechanisms in the development of hand OA