International Labor Standards, Soft Regulation, and National Government Roles

[Excerpt] In this article, we briefly describe the different approaches to the regulation of international labor standards, and then argue for a new role for national governments based on soft rather than hard regulation approaches. We argue that this new role shows potential for significantly enhancing progress in international labor standards, since it enables governments to articulate a position without having to deal with the enforcement issues that hard regulation mandates. We justify this new role for governments based on the increasing use of soft regulation in the international arena. Of course, this approach is not without its own problems, but given that existing approaches have all provided imperfect solutions to the problem of improving labor standards globally, re-visiting the role of national governments is in our view, highly important

Long term evaluation of disease progression through the quantitative magnetic resonance imaging of symptomatic knee osteoarthritis patients: correlation with clinical symptoms and radiographic changes

The objective of this study was to further explore the cartilage volume changes in knee osteoarthritis (OA) over time using quantitative magnetic resonance imaging (qMRI). These were correlated with demographic, clinical, and radiological data to better identify the disease risk features. We selected 107 patients from a large trial (n = 1,232) evaluating the effect of a bisphosphonate on OA knees. The MRI acquisitions of the knee were done at baseline, 12, and 24 months. Cartilage volume from the global, medial, and lateral compartments was quantified. The changes were contrasted with clinical data and other MRI anatomical features. Knee OA cartilage volume losses were statistically significant compared to baseline values: -3.7 ± 3.0% for global cartilage and -5.5 ± 4.3% for the medial compartment at 12 months, and -5.7 ± 4.4% and -8.3 ± 6.5%, respectively, at 24 months. Three different populations were identified according to cartilage volume loss: fast (n = 11; -13.2%), intermediate (n = 48; -7.2%), and slow (n = 48; -2.3%) progressors. The predictors of fast progressors were the presence of severe meniscal extrusion (p = 0.001), severe medial tear (p = 0.005), medial and/or lateral bone edema (p = 0.03), high body mass index (p < 0.05, fast versus slow), weight (p < 0.05, fast versus slow) and age (p < 0.05 fast versus slow). The loss of cartilage volume was also slightly associated with less knee pain. No association was found with other Western Ontario McMaster Osteoarthritis Index (WOMAC) scores, joint space width, or urine biomarker levels. Meniscal damage and bone edema are closely associated with more cartilage volume loss. These data confirm the significant advantage of qMRI for reliably measuring knee structural changes at as early as 12 months, and for identifying risk factors associated with OA progression

Value of biomarkers in osteoarthritis: Current status and perspectives

Osteoarthritis affects the whole joint structure with progressive changes in cartilage, menisci, ligaments and subchondral bone, and synovial inflammation. Biomarkers are being developed to quantify joint remodelling and disease progression. This article was prepared following a working meeting of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis convened to discuss the value of biochemical markers of matrix metabolism in drug development in osteoarthritis. The best candidates are generally molecules or molecular fragments present in cartilage, bone or synovium and may be specific to one type of joint tissue or common to them all. Many currently investigated biomarkers are associated with collagen metabolism in cartilage or bone, or aggrecan metabolism in cartilage. Other biomarkers are related to non-collagenous proteins, inflammation and/or fibrosis. Biomarkers in osteoarthritis can be categorised using the burden of disease, investigative, prognostic, efficacy of intervention, diagnostic and safety classification. There are a number of promising candidates, notably urinary C-terminal telopeptide of collagen type II and serum cartilage oligomeric protein, although none is sufficiently discriminating to differentiate between individual patients and controls (diagnostic) or between patients with different disease severities (burden of disease), predict prognosis in individuals with or without osteoarthritis (prognostic) or perform so consistently that it could function as a surrogate outcome in clinical trials (efficacy of intervention). Future avenues for research include exploration of underlying mechanisms of disease and development of new biomarkers; technological development; the ‘omics’ (genomics, metabolomics, proteomics and lipidomics); design of aggregate scores combining a panel of biomarkers and/or imaging markers into single diagnostic algorithms; and investigation into the relationship between biomarkers and prognosis. This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 3.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial

Multicentre, prospective, open study to evaluate the safety and efficacy of hylan G-F 20 in knee osteoarthritis subjects presenting with pain following arthroscopic meniscectomy

The aim of the study was to evaluate the safety and efficacy of viscosupplementation with hylan G-F 20 in patients with mild to moderate osteoarthritis (OA) presenting with persistent knee pain 4–12 weeks after arthroscopic meniscectomy. A prospective, multi-centre, open study was carried out in patients with pain due to OA of the knee, not resolved by simple analgesics, 4–12 weeks after undergoing arthroscopic meniscectomy. To be eligible, patients had to score ≥50 mm and ≤90 mm on both walking pain and patient global assessment visual analogue scales (VAS; 0–100 mm) at baseline and be radiologically diagnosed pre-operatively with OA grade I or II on the Kellgren-Lawrence scale, with <50% joint space narrowing. Patients received three intra-articular, 2 ml injections of hylan G-F 20 in the target knee with an interval of 1 week between injections, and were followed for 52 weeks. The primary efficacy endpoint was the change from baseline in the walking pain VAS score at 26 weeks. Secondary outcome measures were the walking pain VAS scores at all other time points, the WOMAC Index at all time points, and patient and physician global assessment at all time points. The safety of the treatment was assessed using adverse event (AE) reports. A total of 62 patients (mean age 55.4 years, 52% male) were enrolled. The mean walking pain VAS score decreased by 36.8 mm from baseline at 26 weeks (P < 0.0001), and also showed statistically significant decreases (P < 0.0001) at all other time points. The change in WOMAC total and subscale scores from baseline were statistically significant (P < 0.0001) at all time points, as were the decreases in the physician and patient global assessment VAS scores. There were 18 target knee AEs (mostly pain and/or swelling and/or effusion) in 12 patients (19%) considered to be at least possibly related to treatment. The majority of these (78%) were mild or moderate in intensity. One patient (1.6%) experienced a serious adverse event (synovitis) in the target knee that was considered possibly related to study treatment. Hylan G-F 20 provides effective pain relief and improves stiffness and physical function in patients with mild to moderate OA presenting with persistent osteoarthritic pain 4–12 weeks after arthroscopic meniscectomy. Symptomatic efficacy was maximised at 12 weeks and maintained at 26 and 52 weeks. The type (pain and/or swelling and/or effusion) and the intensity (mostly mild/moderate) of AEs reported in this study are similar to those reported in other trials in different patient populations, but the incidence was higher (19%). The risk/benefit of hylan G-F 20 in this particular population of patients is favourable

Post-traumatic glenohumeral cartilage lesions: a systematic review

<p>Abstract</p> <p>Background</p> <p>Any cartilage damage to the glenohumeral joint should be avoided, as these damages may result in osteoarthritis of the shoulder. To understand the pathomechanism leading to shoulder cartilage damage, we conducted a systematic review on the subject of articular cartilage lesions caused by traumas where non impression fracture of the subchondral bone is present.</p> <p>Methods</p> <p>PubMed (MEDLINE), ScienceDirect (EMBASE, BIOBASE, BIOSIS Previews) and the COCHRANE database of systematic reviews were systematically scanned using a defined search strategy to identify relevant articles in this field of research. First selection was done based on abstracts according to specific criteria, where the methodological quality in selected full text articles was assessed by two reviewers. Agreement between raters was investigated using percentage agreement and Cohen's Kappa statistic. The traumatic events were divided into two categories: 1) acute trauma which refers to any single impact situation which directly damages the articular cartilage, and 2) chronic trauma which means cartilage lesions due to overuse or disuse of the shoulder joint.</p> <p>Results</p> <p>The agreement on data quality between the two reviewers was 93% with a Kappa value of 0.79 indicating an agreement considered to be 'substantial'. It was found that acute trauma on the shoulder causes humeral articular cartilage to disrupt from the underlying bone. The pathomechanism is said to be due to compression or shearing, which can be caused by a sudden subluxation or dislocation. However, such impact lesions are rarely reported. In the case of chronic trauma glenohumeral cartilage degeneration is a result of overuse and is associated to other shoulder joint pathologies. In these latter cases it is the rotator cuff which is injured first. This can result in instability and consequent impingement which may progress to glenohumeral cartilage damage.</p> <p>Conclusion</p> <p>The great majority of glenohumeral cartilage lesions without any bony lesions are the results of overuse. Glenohumeral cartilage lesions with an intact subchondral bone and caused by an acute trauma are either rare or overlooked. And at increased risk for such cartilage lesions are active sportsmen with high shoulder demand or athletes prone to shoulder injury.</p

The effectiveness of pulsed electrical stimulation (E-PES) in the management of osteoarthritis of the knee: a protocol for a randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>Osteoarthritis (OA) of the knee is one of the main causes of musculoskeletal disability in the western world. Current available management options provide symptomatic relief (exercise and self-management, medication and surgery) but do not, in general, address the disease process itself. Moreover, adverse effects and complications with some of these interventions (medication and surgery) and the presence of co-morbidities commonly restrict their use. There is clearly a need to investigate treatments that are more widely applicable for symptom management and which may also directly address the disease process itself.</p> <p>In two randomised controlled trials of four and 12 weeks duration, pulsed electrical stimulation was shown to be effective in managing the symptoms of OA of the knee. Laboratory and animal studies demonstrate the capacity of externally applied electric and electromagnetic fields to positively affect chondrocyte proliferation and extracellular matrix protein production. This latter evidence provides strong theoretical support for the use of electrical stimulation to maintain and repair cartilage in the clinical setting and highlights its potential as a disease-modifying modality.</p> <p>Methods/Design</p> <p>A double-blind, randomised, placebo-controlled, repeated measures trial to examine the effectiveness of pulsed electrical stimulation in providing symptomatic relief for people with OA of the knee over 26 weeks.</p> <p>Seventy people will be recruited and information regarding age, gender, body mass index and medication use will be recorded. The population will be stratified for age, gender and baseline pain levels.</p> <p>Outcome measures will include pain (100 mm VAS and WOMAC 3.1), function (WOMAC 3.1), stiffness (WOMAC 3.1), patient global assessment (100 mm VAS) and quality of life (SF-36). These outcomes will be measured at baseline, four, 16 and 26 weeks. Activity levels will be measured at baseline and 16 weeks using accelerometers and the Human Activity Profile questionnaire. A patient global perceived effect scale (11-point Likert) will be completed at 16 and 26 weeks.</p> <p>Discussion</p> <p>This paper describes the protocol for a randomised, double-blind, placebo-controlled trial that will contribute to the evidence regarding the use of sub-sensory pulsed electrical stimulation in the management of OA of the knee.</p> <p>Trial registration</p> <p>Australian Clinical Trials Registry ACTRN12607000492459.</p

A systematic review of the relationship between subchondral bone features, pain and structural pathology in peripheral joint osteoarthritis

Introduction: Bone is an integral part of the osteoarthritis (OA) process. We conducted a systematic literature review in order to understand the relationship between non-conventional radiographic imaging of subchondral bone, pain, structural pathology and joint replacement in peripheral joint OA. Methods: A search of the Medline, EMBASE and Cochrane library databases was performed for original articles reporting association between non-conventional radiographic imaging-assessed subchondral bone pathologies and joint replacement, pain or structural progression in knee, hip, hand, ankle and foot OA. Each association was qualitatively characterised by a synthesis of the data from each analysis based upon study design, adequacy of covariate adjustment and quality scoring. Results: In total 2456 abstracts were screened and 139 papers were included (70 cross-sectional, 71 longitudinal analyses; 116 knee, 15 hip, six hand, two ankle and involved 113 MRI, eight DXA, four CT, eight scintigraphic and eight 2D shape analyses). BMLs, osteophytes and bone shape were independently associated with structural progression or joint replacement. BMLs and bone shape were independently associated with longitudinal change in pain and incident frequent knee pain respectively. Conclusion: Subchondral bone features have independent associations with structural progression, pain and joint replacement in peripheral OA in the hip and hand but especially in the knee. For peripheral OA sites other than the knee, there are fewer associations and independent associations of bone pathologies with these important OA outcomes which may reflect fewer studies; for example the foot and ankle were poorly studied. Subchondral OA bone appears to be a relevant therapeutic target. Systematic review: PROSPERO registration number: CRD 4201300500

Radiographic assessment of the femorotibial joint of the CCLT rabbit experimental model of osteoarthritis

<p>Abstract</p> <p>Background</p> <p>The purposes of the study were to determine the relevance and validity of in vivo non-invasive radiographic assessment of the CCLT (Cranial Cruciate Ligament Transection) rabbit model of osteoarthritis (OA) and to estimate the pertinence, reliability and reproducibility of a radiographic OA (ROA) grading scale and associated radiographic atlas.</p> <p>Methods</p> <p>In vivo non-invasive extended non weight-bearing radiography of the rabbit femorotibial joint was standardized. Two hundred and fifty radiographs from control and CCLT rabbits up to five months after surgery were reviewed by three readers. They subsequently constructed an original semi-quantitative grading scale as well as an illustrative atlas of individual ROA feature for the medial compartment. To measure agreements, five readers independently scored the same radiographic sample using this atlas and three of them performed a second reading. To evaluate the pertinence of the ROA grading scale, ROA results were compared with gross examination in forty operated and ten control rabbits.</p> <p>Results</p> <p>Radiographic osteophytes of medial femoral condyles and medial tibial condyles were scored on a four point scale and dichotomously for osteophytes of medial fabella. Medial joint space width was scored as normal, reduced or absent. Each ROA features was well correlated with gross examination (p < 0.001). ICCs of each ROA features demonstrated excellent agreement between readers and within reading. Global ROA score gave the highest ICCs value for between (ICC 0.93; CI 0.90-0.96) and within (ICC ranged from 0.94 to 0.96) observer agreements. Among all individual ROA features, medial joint space width scoring gave the highest overall reliability and reproducibility and was correlated with both meniscal and cartilage macroscopic lesions (r_s= 0.68 and r_s= 0.58, p < 0.001 respectively). Radiographic osteophytes of the medial femoral condyle gave the lowest agreements while being well correlated with the macroscopic osteophytes (r_s= 0.64, p < 0.001).</p> <p>Conclusion</p> <p>Non-invasive in vivo radiography of the rabbit femorotibial joint is feasible, relevant and allows a reproducible grading of experimentally induced OA lesion. The radiographic grading scale and atlas presented could be used as a template for in vivo non invasive grading of ROA in preclinical studies and could allow future comparisons between studies.</p

Quantitative bone marrow lesion size in osteoarthritic knees correlates with cartilage damage and predicts longitudinal cartilage loss

<p>Abstract</p> <p>Background</p> <p>Bone marrow lesions (BMLs), common osteoarthritis-related magnetic resonance imaging findings, are associated with osteoarthritis progression and pain. However, there are no articles describing the use of 3-dimensional quantitative assessments to explore the longitudinal relationship between BMLs and hyaline cartilage loss. The purpose of this study was to assess the cross-sectional and longitudinal descriptive characteristics of BMLs with a simple measurement of approximate BML volume, and describe the cross-sectional and longitudinal relationships between BML size and the extent of hyaline cartilage damage.</p> <p>Methods</p> <p>107 participants with baseline and 24-month follow-up magnetic resonance images from a clinical trial were included with symptomatic knee osteoarthritis. An 'index' compartment was identified for each knee defined as the tibiofemoral compartment with greater disease severity. Subsequently, each knee was evaluated in four regions: index femur, index tibia, non-index femur, and non-index tibia. Approximate BML volume, the product of three linear measurements, was calculated for each BML within a region. Cartilage parameters in the index tibia and femur were measured based on manual segmentation.</p> <p>Results</p> <p>BML volume changes by region were: index femur (median [95% confidence interval of the median]) 0.1 cm³(-0.5 to 0.9 cm³), index tibia 0.5 cm³(-0.3 to 1.7 cm³), non-index femur 0.4 cm³(-0.2 to 1.6 cm³), and non-index tibia 0.2 cm³(-0.1 to 1.2 cm³). Among 44 knees with full thickness cartilage loss, baseline tibia BML volume correlated with baseline tibia full thickness cartilage lesion area (<it>r </it>= 0.63, <it>p</it>< 0.002) and baseline femur BML volume with longitudinal change in femoral full thickness cartilage lesion area (<it>r </it>= 0.48 <it>p</it>< 0.002).</p> <p>Conclusions</p> <p>Many regions had no or small longitudinal changes in approximate BML volume but some knees experienced large changes. Baseline BML size was associated to longitudinal changes in area of full thickness cartilage loss.</p