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Aims Hyperuricaemia and gout are strongly related with traditional cardiovascular risk factors and vascular damage. This study aimed to assess whether febuxostat and allopurinol could differently influence carotid-femoral pulse wave velocity (cfPWV) in patients with gout and elevated serum uric acid (SUA) levels. Methods and results A multi-centre, multinational, phase IV, randomized, parallel-group, active-controlled, open-label trial with blind endpoints evaluation. One hundred and ninety-seven adults with gout and SUA levels ≥8 mg/dL were randomized to febuxostat or allopurinol in a 1:1 ratio for 36 weeks. The primary outcome was the comparison of the effects of febuxostat and allopurinol on changes in cfPWV. The mean cfPWV values at randomization and Week 36 were 8.69 and 9.00 m/s, respectively for subjects randomized to febuxostat and 9.02 and 9.05 m/s for subjects randomized to allopurinol. No statistically significant changes in cfPWV by treatment assignment were observed at any time point for any of the assessed parameters. More subjects who received febuxostat had serum urate concentrations ≤6 mg/dL following treatment (78.3% vs. 61.1% at Week 36, P = 0.0137). Treatment-emergent adverse events were reported by 51 (52.0%) patients randomized to febuxostat and 63 (62.5%) patients randomized to allopurinol. The majority of events were mild in both treatment groups and included gout flares and arthralgia. Conclusion In patients with gout and elevated SUA levels the arterial stiffness remained stable both with febuxostat and allopurinol. Febuxostat was more effective and faster than allopurinol in achieving the SUA target. Both treatments were safe and well tolerated.

Objective To investigate the association between neutrophil activation and cardiovascular risk in gout patients. We hypothesize that neutrophil activation mediates inflammation and therefore takes part in atherogenesis in gout patients. Method Patient data were collected from 75 consecutive gout patients participating in the Reade gout cohort Amsterdam. Levels of neutrophil extracellular traps (NETs) and neutrophil activation (calprotectin and peroxidase activity) were analysed by ELISA and fluorimetry in plasma and compared with healthy controls. Markers of neutrophil activation were related to clinical markers of cardiovascular risk, including BMI, smoking, blood pressure, lipid profile and 10 year risk of cardiovascular mortality (EU-SCORE). Results Increased levels of NETs were found in gout patients, although increased levels were not associated with cardiovascular risk. However, markers of neutrophil activation, including peroxidase activity correlated with waist:hip ratio (β = 0.33, P Conclusion We demonstrated elevated levels of neutrophil activation markers, MPO and calprotectin in gout patients as compared with healthy controls. Of note, neutrophil activation markers were associated with several risk factors for cardiovascular disease, including hyperlipidaemia, hypertension and diabetes. Finally, the presence of a neutrophil activation signature was strongly associated with an increased 10 year risk of cardiovascular mortality. Further studies are needed to determine whether gout-specific factors and/or cardiovascular risk factors contribute to the elevated neutrophil activation observed in these patients.

Much to the liking of many geographers, Forbes Magazine’s contributor and professor in meteorology at the University of Georgia, J. Marshall Shepherd, wrote in early March 2020 an op‐ed titled ‘Why Geography is a key part of fighting the COVID‐19 Coronavirus outbreak’. In Wired, David Wolman (2020) wrote how the pandemic is redefining our relationship with space in a contribution titled ‘Amid a Pandemic, Geography Returns with a Vengeance’. Notwithstanding the many challenges that the Covid‐19 pandemic poses, both in our private lives and in our professional activities, it offers a great opportunity for analysis through a geographic lens. Geographical knowledge and geospatial data, perhaps best exemplified by the widely used Johns Hopkins University COVID‐19 tracking website, have already proven to be vital for understanding the pandemic’s reach. The uneven distribution of the virus across and within countries raises inherently geographic questions regarding the political, economic, financial, socio‐cultural and demographic dimensions of the pandemic. The aim of this special issue of Tijdschrift voor Economische en Sociale Geografie (TESG) is to present the initial investigations of geographers and socio‐spatial scientists into the emerging spaces of the effects of the COVID‐19 pandemic. Following a call, we have received well over 40 papers, thereby exceeding our expectations. After internal and external review of the papers we here present the papers that were selected for publication. We are thankful to the reviewers who provided fast, yet detailed, feedback on the papers. In addition, we would like to thank Grace Ong, Senior Journals Publishing Editor at Wiley, and Noel Valdivia, Production Editor, for their support in the publication of this special issue. The papers in this special issue present an interesting geographical mix (with case studies from Asia, Europe and the North America) as well as a variety of methodological approaches towards understanding the spatial manifestations and variegated geographic impact of the pandemic. Furthermore, they well represent the different thematic fields in geography. The editors of TESG welcome more papers on the consequences of the COVID‐19 pandemic, which we will have reviewed as we do with any other paper. We will not be able to fast‐track new submissions but we will publish new papers online in ‘Early View’ soon after they have been accepted for publication. Future papers on COVID‐19 will also be added to a Virtual Special Issue, which will consist of all papers published in this issue together with new papers on the geography of the pandemic. As much as possible we aim for the open access publication of these papers. The papers in this special issue are grouped by theme and in the remainder of this editorial we will briefly introduce these different themes.

Experimentalist forms of governance have burgeoned across policy areas and institutional contexts in recent years. Recognizing that experimentalist forms of governance can evolve along a plethora of distinct pathways, this paper inquires how the evolutionary nature of experimentalism can be explored in greater depth. Linking the framework of experimentalist governance to that of Evolutionary Governance Theory (EGT), the paper identifies three driving mechanisms of contingency in experimentalism: governance being (1) self-referential, (2) rooted in observation, and (3) steered by dependencies. The paper then refers to recent efforts in the realm of energy transition governance in the Netherlands to illustrate how these contingency mechanisms can help to interrogate the variegated evolutionary pathways that experimentalist governance may have in practice. Building on this Dutch empirical context, the paper puts forward evolutionary path- and context-mapping as a fruitful tool for identifying and disentangling the myriad of pathways along which experimentalism may manifest itself.

Objective: To examine the performance of ultrasound (US) for the diagnosis of gout using the presence of monosodium urate monohydrate (MSU) crystals as the gold standard. Methods: We analyzed data from the Study for Updated Gout Classification Criteria (SUGAR), a large, multicenter observational cross-sectional study of consecutive subjects with at least 1 swollen joint who conceivably may have gout. All subjects underwent arthrocentesis; cases were subjects with confirmed MSU crystals. Rheumatologists or radiologists who were blinded with regard to the results of the MSU crystal analysis performed US on 1 or more clinically affected joints. US findings of interest were double contour sign, tophus, and snowstorm appearance. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. Multivariable logistic regression models were used to examine factors associated with positive US results among subjects with gout. Results: US was performed in 824 subjects (416 cases and 408 controls). The sensitivity, specificity, PPV, and NPV for the presence of any 1 of the features were 76.9%, 84.3%, 83.3%, and 78.2%, respectively. Sensitivity was higher among subjects with a disease duration of ≥2 years and among subjects with subcutaneous nodules on examination (suspected tophus). Associations with a positive US finding included suspected clinical tophus (odds ratio [OR] 4.77 [95% confidence interval (95% CI) 2.23–10.21]), any abnormality on plain radiography (OR 4.68 [95% CI 2.68–8.17]), and serum urate level (OR 1.31 [95% CI 1.06–1.62]). Conclusion: US features of MSU crystal deposition had high specificity and high PPV but more limited sensitivity for early gout. The specificity remained high in subjects with early disease and without clinical signs of tophi. (Less)

The objective of this study was to evaluate whether self-reported knee instability is associated with activity limitations in patients with knee osteoarthritis (OA), in addition to knee pain and muscle strength. A cohort of 248 patients diagnosed with knee OA was examined. Self-reported knee instability was defined as the perception of any episode of buckling, shifting, or giving way of the knee in the past 3 months. Knee pain was assessed using a numeric rating scale, and knee extensor and flexor strength were measured using an isokinetic dynamometer. Activity limitations were measured by using the Western Ontario and McMasters Universities Osteoarthritis Index physical function questionnaire, the timed Get Up and Go, and the timed stair climbing and three questionnaires evaluating walking, climbing stairs, and rising from a chair. Other potential determinants of activity limitations were also collected, including joint proprioception, joint laxity, age, sex, body mass index (BMI), disease duration, and radiographic disease severity. Regression analyses evaluated the effect of adding self-reported knee instability to knee pain and muscle strength, when examining associations with the activity limitations measures. Self-reported knee instability was common (65 %) in this cohort of patients with knee OA. Analyses revealed that self-reported knee instability is significantly associated with activity limitations, even after controlling for knee pain and muscle strength. Joint proprioception, joint laxity, age, sex, BMI, duration of complaints, and radiographic severity did not confound the associations. In conclusion, self-reported knee instability is associated with activity limitations in patients with knee OA, in addition to knee pain and muscle strength. Clinically, self-reported knee instability should be assessed in addition to knee pain and muscle strength.

Background Recently, an American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) collaboration developed new classification criteria for rheumatoid arthritis (RA). Objective To evaluate the diagnostic and discriminative ability of these new criteria compared with the 1987 ACR criteria and the Visser decision rule. Methods 455 patients with early arthritis were studied. The diagnostic performance of the criteria was evaluated using methotrexate treatment within 1 year, expert opinion RA and erosive disease as ‘gold standards’. Erosive disease was defined as a 0–3 year change in radiographic score of ≥5. Results The discriminative ability of the three criteria sets (2010 ACR/EULAR, 1987 ACR criteria and Visser algorithm) was similar with areas under the curve of 0.71–0.78 (‘gold standard’ methotrexate), 0.74–0.80 (gold standard expert opinion RA) and 0.63–0.67 (gold standard erosive disease after 3 years). The sensitivity of the 2010 ACR/EULAR criteria was highest with 0.85 (gold standard methotrexate). 86% of patients with RA and 51% of ‘non-RA’ patients according to the new criteria used methotrexate. Conclusion The 2010 ACR/EULAR criteria were slightly more sensitive, but otherwise performed similarly to the older criteria. A high percentage of ‘non-RA’ patients used methotrexate, the gold standard for RA. The ability of the new criteria to identify patients with erosive disease was low, possibly owing to the effect of intensive treatment.

INTRODUCTION: We aimed to explore the associations between knee osteoarthritis (OA)-related tissue abnormalities assessed by conventional radiography (CR) and by high-resolution 3.0 Tesla magnetic resonance imaging (MRI), as well as biomechanical factors and findings from physical examination in patients with knee OA.METHODS: This was an explorative cross-sectional study of 105 patients with knee OA. Index knees were imaged using CR and MRI. Multiple features from CR and MRI (cartilage, osteophytes, bone marrow lesions, effusion and synovitis) were related to biomechanical factors (quadriceps and hamstrings muscle strength, proprioceptive accuracy and varus-valgus laxity) and physical examination findings (bony tenderness, crepitus, bony enlargement and palpable warmth), using multivariable regression analyses.RESULTS: Quadriceps weakness was associated with cartilage integrity, effusion, synovitis (all detected by MRI) and CR-detected joint space narrowing. Knee joint laxity was associated with MRI-detected cartilage integrity, CR-detected joint space narrowing and osteophyte formation. Multiple tissue abnormalities including cartilage integrity, osteophytes and effusion, but only those detected by MRI, were found to be associated with physical examination findings such as crepitus.CONCLUSION: We observed clinically relevant findings, including a significant association between quadriceps weakness and both effusion and synovitis, detected by MRI. Inflammation was detected in over one-third of the participants, emphasizing the inflammatory component of OA and a possible important role for anti-inflammatory therapies in knee OA. In general, OA-related tissue abnormalities of the knee, even those detected by MRI, were found to be discordant with biomechanical and physical examination features.