Safety of celecoxib and nonselective nonsteroidal anti-inflammatory drugs in juvenile idiopathic arthritis: results of the phase 4 registry

BACKGROUND: This study aimed to assess long-term safety and developmental data on juvenile idiopathic arthritis (JIA) patients treated in routine clinical practice with celecoxib or nonselective nonsteroidal anti-inflammatory drugs (nsNSAIDs). METHODS: Children aged ≥2 to <18 years with rheumatoid-factor–positive or –negative polyarthritis, persistent or extended oligoarthritis, or systemic arthritis were enrolled into this prospective, observational, multicenter standard-of-care registry. Eligible patients were newly or recently prescribed (≤6 months) an nsNSAID or celecoxib. Enrolled patients were followed to the end of the study, whether they remained on the original NSAID, switched, or discontinued therapy altogether. All adverse events (AEs) regardless of severity were captured in the database. RESULTS: A total of 274 patients (nsNSAID, n = 219; celecoxib, n = 55) were observed for 410 patient-years of observation. Naproxen, meloxicam, and nabumetone were the most frequently used nsNSAIDs. At baseline, the celecoxib group was older, had a numerically longer median time since diagnosis, and a numerically higher proportion of patients with a history of gastrointestinal-related NSAID intolerance. AEs reported were those frequently observed with NSAID treatment and were similar across groups (nsNSAIDs: 52.0%; celecoxib: 52.9%). Twelve unique patients experienced a total of 18 serious AEs; the most frequent were infections, and none was attributed to NSAID use. CONCLUSIONS: The safety profile of celecoxib and nsNSAIDs appears similar overall. The results from this registry, ongoing pharmacovigilance, and the phase 3 trial that led to the approval of celecoxib for children with JIA provide evidence that the benefit-risk for celecoxib treatment in JIA remains positive. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT00688545

High Levels of DEK Autoantibodies in Sera of Patients With Polyarticular Juvenile Idiopathic Arthritis and With Early Disease Flares Following Cessation of Antiâ Tumor Necrosis Factor Therapy

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142962/1/art40404_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142962/2/art40404-sup-0001-Supinfo.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142962/3/art40404.pd

Plasticity in dendroclimatic response across the distribution range of Aleppo pine (Pinus halepensis)

We investigated the variability of the climate-growth relationship of Aleppo pine across its distribution range in the Mediterranean Basin. We constructed a network of tree-ring index chronologies from 63 sites across the region. Correlation function analysis identified the relationships of tree-ring index to climate factors for each site. We also estimated the dominant climatic gradients of the region using principal component analysis of monthly, seasonal, and annual mean temperature and total precipitation from 1,068 climatic gridpoints. Variation in ring width index was primarily related to precipitation and secondarily to temperature. However, we found that the dendroclimatic relationship depended on the position of the site along the climatic gradient. In the southern part of the distribution range, where temperature was generally higher and precipitation lower than the regional average, reduced growth was also associated with warm and dry conditions. In the northern part, where the average temperature was lower and the precipitation more abundant than the regional average, reduced growth was associated with cool conditions. Thus, our study highlights the substantial plasticity of Aleppo pine in response to different climatic conditions. These results do not resolve the source of response variability as being due to either genetic variation in provenance, to phenotypic plasticity, or a combination of factors. However, as current growth responses to inter-annual climate variability vary spatially across existing climate gradients, future climate-growth relationships will also likely be determined by differential adaptation and/or acclimation responses to spatial climatic variation. The contribution of local adaptation and/or phenotypic plasticity across populations to the persistence of species under global warming could be decisive for prediction of climate change impacts across populations. In this sense, a more complex forest dynamics modeling approach that includes the contribution of genetic variation and phenotypic plasticity can improve the reliability of the ecological inferences derived from the climate-growth relationships.This work was partially supported by Spanish Ministry of Education and Science co-funded by FEDER program (CGL2012-31668), the European Union and the National Ministry of Education and Religion of Greece (EPEAEK- Environment – Archimedes), the Slovenian Research Agency (program P4-0015), and the USDA Forest Service. The cooperation among international partners was supported by the COST Action FP1106, STREeSS

On the stability of long-range sound propagation through a structured ocean

Several acoustic experiments show a surprising degree of stability in wave fronts propagating over multi-megameter ranges through the ocean's sound channel despite the presence of random-like, sound speed fluctuations. Previous works have pointed out the existence of chaos in simplified ray models incorporating structure inspired by the true ocean environment. A ``predictability horizon'' has been introduced beyond which stable wave fronts cease to exist and point-wise, detailed comparisons between even the most sophisticated models and experiment may be limited for fundamental reasons. We find, by applying one of the simplified models, that for finite ranges, the fluctuations of the ray stabilities are very broad and consistent with lognormal densities. A fraction of the rays retain a much more stable character than the typical ray. This may be one of several possible mechanisms leading to greater than anticipated sound field stability. The lognormal ray stability density may underlie the recent, experimentally determined, lognormal density of wave field intensities [J. Acoust. Soc. Am. 105 (1999) 3202--18].Comment: submitted to "J. Acoust. Soc. Am." 16 Feb 2000. 12 pages, 8 figs (eps) to be presented at Annual APS March Meeting 2000, session K25, 9 AM Wednesda

A44: High Levels of DEK Autoantibodies May Predict Early Flare Following Cessation of Anti‐TNF Therapy

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106772/1/art38460.pd