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Background Context: There are no previous epidemiologic studies examining associations between physical activity and imaging-detected lumbar zygapophyseal joint osteoarthritis (ZJO) in a community-based sample.Purpose: To determine whether physical activity is associated with prevalent lumbar ZJO on computed tomography (CT).Study Design/setting: A community-based cross-sectional study.Patient Sample: Four hundred twenty-four older adults from the Framingham Heart Study.Outcome Measures: Participants received standardized CT assessments of lumbar ZJO at the L2-S1 levels. Severe lumbar ZJO was defined according to the presence and/or degree of joint space narrowing, osteophytosis, articular process hypertrophy, articular erosions, subchondral cysts, and intra-articular vacuum phenomenon. This definition of lumbar ZJO was based entirely on CT imaging findings and did not include any clinical criteria such as low back pain.Methods: Physical activity was measured using the Physical Activity Index, which estimate hours per day typically spent in these activity categories: sleeping, sitting, slight activity, moderate activity, and heavy activity. Participants reported on usual frequency of walking, running, swimming, and weightlifting. We used multivariable logistic regression to examine associations between self-reported activity and severe lumbar ZJO, while adjusting for key covariates including age, sex, height, and weight.Results: In multivariable analyses, ordinal categories of heavy physical activity duration per day were significantly associated with severe lumbar ZJO (p for trend=.04), with the greatest risk observed for the category 3 or more hours per day, odds ratio 2.13 (95% confidence interval [CI] 0.97-4.67). When heavy activity was modeled as a continuous independent variable, each hour was independently associated with 1.19 times the odds of severe lumbar ZJO (95% CI 1.03-1.38, p=.02). Less vigorous types of physical activity and the type of exercise were not associated with severe lumbar ZJO. Older age, lesser height, and greater weight were independently and significantly associated with severe lumbar ZJO. In multivariable models predicting lumbar ZJO, neither model discrimination nor reclassification improved with the addition of physical activity variables, compared with a multivariable model including age, sex, height, and weight.Conclusions: Our findings demonstrate a statistically significant cross-sectional association between heavy physical activity and CT-detected severe lumbar ZJO. However, the additional discriminatory capability of heavy physical activity above and beyond that contributed by other factors was negligible. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a leading cause of disability worldwide. Clinical practice guidelines (CPGs) have been developed to facilitate improved OA management. Scientific communities worldwide have proposed CPGs for OA treatment. Despite the number of highly prominent guidelines available and their remarkable consistency, their uptake has been suboptimal. Possibly because of the multitude of barriers related to the implementation of CPGs. For example, different guidelines show contradictions, some lack evidence, and they lack a hierarchy or tools to facilitate their translation and application. Also, the guidelines do not acknowledge the effect of comorbidities on choosing the treatments. Finally, poor integration of multidisciplinary services within and across healthcare settings is a major barrier to the effective implementation of management guidelines. Here we describe the main problems related to the OA guidelines and some solutions so as to offer some guidance on the elaboration of future CPGs and their implementation in primary care. [ABSTRACT FROM AUTHOR]

Striking differences exist in outcomes for cancer between developed countries with comparable healthcare systems. We compare the healthcare systems of 3 countries (Denmark, Norway, Sweden), 3 UK jurisdictions (England, Wales and Northern Ireland), 3 Canadian provinces (British Columbia, Manitoba, Ontario) and 2 Australian states (New South Wales, Victoria) using a framework which assesses the possible contribution of primary care systems to a range of health outcomes, drawing on key characteristics influencing population health. For many of the characteristics we investigated there are no significant differences between those countries with poorer cancer outcomes (England and Denmark) and the rest. In particular, regulation, financing, the existence of patient lists, the GP gatekeeping role, direct access to secondary care, the degree of comprehensiveness of primary care services, the level of cost sharing and the type of primary care providers within healthcare systems were not specifically and consistently associated with differences between countries. Factors that could have an influence on patient and professional behaviour, and consequently contribute to delays in cancer diagnosis and poorer cancer outcomes in some countries, include centralisation of services, free movement of patients between primary care providers, access to secondary care, and the existence of patient list systems. It was not possible to establish a causal correlation between healthcare system characteristics and cancer outcomes. Further studies should explore in greater depth the associations between single health system factors and cancer outcomes, recognising that in complex systems where context is all-important, it will be difficult to establish causal relationships. Better understanding of the interaction between healthcare system variables and patient and professional behaviour may generate new hypotheses for further research. [ABSTRACT FROM AUTHOR]

We compared the assessment of active synovitis in knee osteoarthritis (OA) by utilising superb microvascular imaging (SMI) and conventional power Doppler (cPD) techniques, and then correlated each technique with paients' symptoms, radiographic features and magnetic resonance imaging (MRI)-detected synovitis. A subgroup of participants with symptomatic knee OA underwent dynamic ultrasound assessment for semi-quantitative scores for SMI and cPD in the suprapatellar, medial and lateral parapatellar knee recesses. Knee pain and other symptoms were evaluated with the knee injury and osteoarthritis outcome score (KOOS). OA severity was assessed using the Kellgren and Lawrence grade (KLG) on radiograph and effusion-synovitis and Hoffa's synovitis score of MRI osteoarthritis knee score on non-contrast-enhanced MRI sequences. The χ2 test and κ statistics were conducted to compare detectability of SMI and cPD for low-grade inflammation, and the Spearman's correlation and Fisher's r to z transformation were conducted to compare correlations of both techniques with symptoms and imaging severity. A total of 89 participants were included in the analyses. SMI increased the detection rate by 25.5% for grade 0 cPD, by 35.4% for grade 1 cPD and by 9% for grade 2 cPD. SMI showed significant correlations with KOOS symptoms, KLG, MRI effusion-synovitis and Hoffa's synovitis scores (r = -0.24 [-0.45, -0.01]; r = 0.31 [0.10, 0.50]; r = 0.49 [0.33, 0.63]; and r = 0.54 [0.37, 0.68]). The cPD was significantly correlated with KOOS pain, other symptoms, MRI effusion-synovitis and Hoffa's synovitis (r = -0.23 [-0.44, -0.01]; r = -0.29 [-0.49, -0.06]; r = 0.46 [0.28, 61], r = 0.46 [0.25, 0.63]). However, no significant differences were detected in their extent of correlations. SMI can detect low-grade inflammation implicated in OA disease better than cPD and reveal a significant correlation with symptoms, radiographic features and MRI synovitis. The added clinical value of SMI over cPD is still not clear. [ABSTRACT FROM AUTHOR]

• This is the first osteoarthritis clinical trial to utilise activity tracker-recorded outcomes. • Activity trackers are a feasible measurement tool in a clinical trial context. • Behavioural and physical activity change was observed via step count and load rate. • Activity tracker-recorded outcomes did not show significant responsiveness or validity. In osteoarthritis (OA) clinical trials, reliable and responsive outcome measures to document physical and functional improvements are limited. This study aimed to assess whether the use of an activity tracker in an OA clinical trial is a responsive measurement tool. Secondary objectives assessed feasibility and validity. We recruited 65 participants in a prospective cohort study nested in a placebo-controlled clinical trial of platelet-rich plasma injection in knee OA. Participants wore an activity tracker (Fitbit Flex 2), and a smartphone was preloaded with a mobile application (OApp) designed to monitor load rates as a surrogate of knee loading. Participants used the systems for 7 days at baseline and for 7 days before the 2-month follow-up assessment. Effect size (ES) and standardised response mean (SRM) were calculated for change in step count and knee loading rate and regularly used knee OA outcome measures. Correlation coefficients (r) were calculated to examine the strength of the association between outcome measures.. Step count showed a trivial ES and SRM and mean knee loading rate measurements a moderate ES and SRM. We found a weak but significant correlation between change in mean steps per day and global improvement overall (r = 0.28) and Western Ontario and McMaster Universities Osteoarthritis Index function (r = -0.28). Compliance was high with the activity trackers. Despite good feasibility, this study did not show significant responsiveness or validity of the activity trackers as compared with currently recommended outcome measures in OA clinical trials. The main challenge is the lack of a gold standard outcome measure to validate against, and because of the complex interplay between pain and measured function, a lack of correlation does not necessarily represent a failed validation in this context. ACTRN12617000853347. This trial is a substudy of the "Platelet-rich plasma as a symptom-and disease-modifying treatment for knee osteoarthritis – the RESTORE trial". [ABSTRACT FROM AUTHOR]

Natural IgM antibodies (nIgM) are polyreactive autoantibodies that have diverse roles in regulating autoimmunity, systemic inflammation and removal of oxidized low-density lipoproteins (oxLDL). We hypothesized that aberrant states of nIgM may exist in persons with osteoarthritis (OA) and rheumatoid arthritis (RA). Herein, we characterized and compared the levels of nIgM specific for phosphorylcholine (anti-PC), double-stranded DNA (anti-dsDNA), and galactosyl (anti-Gal) in persons with OA, RA and healthy controls (HC). Levels of anti-PC nIgM in OA patients were significantly lower than both HC and RA patients in an age-adjusted analysis ( P < 0.05). In contrast, anti-Gal nIgM levels were significantly higher in RA patients than OA patients ( P < 0.05) and markedly increased in comparison to HC. Anti-PC nIgM significantly correlated with anti-dsDNA and anti-Gal nIgM levels in HC and RA (P < 0.05) but not in OA patients. Elevated CRP levels were associated with RA conditions and old ages in general. There was no significant correlation between anti-PC nIgM and CRP or oxLDL levels. Our study highlights for the first time the evidence of aberrant state of nIgM in human OA compared to healthy individuals that implicates a deficiency in immune responses to oxLDL which may contribute to the metabolic syndromes in the development of OA. [ABSTRACT FROM AUTHOR]

To assess the long-term neurological safety of tanezumab, a monoclonal antibody against nerve growth factor. Patients with osteoarthritis of the hip or knee received stable doses of oral nonsteroidal anti-inflammatory drugs (NSAIDs) before study entry and during a ≤ 37-day screening period. Patients were randomized 1:1:1 to double-dummy tanezumab (2.5 mg or 5 mg, subcutaneous every 8 weeks) or oral NSAIDs (twice-daily) for 56 weeks, with a 24-week follow-up. Neurological safety evaluation focused on peripheral and sympathetic adverse events (AEs), neurologic examinations, and consultations with blinded, external diagnostic reviews. During the treatment period, 6.2%, 9.0%, and 4.6% of patients experienced AEs of abnormal peripheral sensation (APS) in the tanezumab 2.5 mg, 5 mg, and NSAID groups, respectively. Hypoesthesia, paresthesia, and carpal tunnel syndrome were the most common AEs of APS. Clinically significant worsening on examination occurred in <1% in any treatment group at the last study assessment. Diagnoses following external neurological consultation included mononeuropathy (1.3%, 2.1%, and 1.0%), radiculopathy (0.9%, 0.4%, and 0.5%), and polyneuropathy (0.3%, 0.5%, and 0%) in tanezumab 2.5 mg, 5 mg, and NSAID groups, respectively. AEs potentially associated with sympathetic neuropathy were reported for 1.8%, 2.3%, and 2.9% of patients in the tanezumab 2.5 mg, 5 mg, and NSAID groups, respectively. No patient was diagnosed with sympathetic neuropathy. Tanezumab had an increased incidence of AEs of APS versus NSAID; these were typically mild/moderate in severity, resolved during the study, and rarely resulted in discontinuation. Tanezumab was not associated with peripheral neuropathy and did not adversely affect the sympathetic nervous system. ClinicalTrials.gov Identifier NCT02528188 (https://clinicaltrials.gov/ct2/show/NCT02528188). • Tanezumab was associated with adverse events of abnormal peripheral sensation. • Adverse events were infrequent and typically mild to moderate in severity. • Most adverse events resolved during the study and rarely caused discontinuation. • Tanezumab was not associated with peripheral polyneuropathy. • There was no evidence of an effect on sympathetic nervous system function. [ABSTRACT FROM AUTHOR]

The Intensive Diet and Exercise for Arthritis (IDEA) trial was an 18-month randomized controlled trial that enrolled 454 overweight and obese older adults with symptomatic and radiographic knee osteoarthritis (OA). Participants were randomized to either exercise (E), intensive diet-induced weight loss (D), or intensive diet-induced weight loss plus exercise (D + E) interventions. We previously reported that the clinical benefits of D + E were significantly greater than with either intervention alone (e.g., greater pain reduction, and better function, mobility, and health-related quality of life). We now test the hypothesis that D + E has greater overall benefit on gait mechanics compared to either intervention alone. Knee joint loading was analyzed using inverse dynamics and musculoskeletal modeling. Analysis of covariance determined the interventions' effects on gait. The D + E group walked significantly faster at 18-month follow-up (1.35 m s−1) than E (1.29 m s−1, p = 0.0004) and D (1.31 m s−1, p = 0.0007). Tibiofemoral compressive impulse was significantly lower (p = 0.0007) in D (1069 N s) and D + E (1054 N s) compared to E (1130 N s). D had significantly lower peak hip external rotation moment (p = 0.01), hip abduction moment (p = 0.0003), and peak hip power production (p = 0.016) compared with E. Peak ankle plantar flexion moment was significantly less (p < 0.0001) in the two diet groups compared with E. There also was a significant dose-response to weight loss; participants that lost >10% of baseline body weight had significantly (p = 0.0001) lower resultant knee forces and lower muscle (quadriceps, hamstring, and gastrocnemius) forces than participants that had less weight loss. Compared to E, D produces significant load reductions at the hip, knee, and ankle; combining D with E attenuates these reductions, but most remain significantly better than with E alone. [ABSTRACT FROM AUTHOR]