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Objective: To identify the clinical features of elderly-onset rheumatoid arthritis (EORA) and their impact on disease outcome. Methods: A total of 3169 rheumatoid arthritis (RA) patients were recruited as part of the Korean Observational Study Network for Arthritis, the nationwide cohort of South Korea. Patients were stratified according to age at disease onset: <40 years (younger age-onset RA, n = 1167), between the ages of 40 and 59 (middle-aged-onset RA, n = 1516), and ≥60 years (EORA, n = 486). To evaluate the significance of differences in clinical features among these 3 groups, we performed analysis of variance (anova) and the χ2 test. We used multivariable logistic regression analysis to examine the association of onset age with functional disability measured with Health Assessment Questionnaire-Disability Index (HAQDI). Results: EORA patients were associated with high HAQDI (≥1) in bivariable analysis [odds ratio (OR) 1.36, confidence interval (CI) 1.04-1.77]. However, in multivariable analysis, not elderly onset but patients'' age, female gender, high disease activity, disease duration over 10 years, and comorbidity with cardiovascular disease were associated with high HAQDI. Only in a predefined subgroup with disease duration <10 years, elderly onset was an independent influencing factor for the functional disability of RA patients (OR 3.04, CI 1.85-5.67: disease duration of <5 years, OR 3.07, CI 1.64-5.74: disease duration of 5 to 10 years). Conclusions: Disease onset in older age was associated independently with functional disability of RA patients who have relatively short disease duration. [Copyright &y& Elsevier]

Objectives: The object of this study was to introduce the KORean Observational study Network for Arthritis (KORONA) registry with an emphasis on the design of the Korean rheumatoid arthritis (RA) national database, as well as to provide an overview of the RA patients who are currently registered in KORONA. Methods: The KORONA was established in July 2009 by the Clinical Research Center for Rheumatoid Arthritis (CRCRA) in South Korea. KORONA is based on a prospective protocol and standard, defined data collection instruments. Demographic and clinical features, laboratory and radiologic data, health-related outcomes, treatment side effects, resource utilization, and health behaviors of the RA cohort patients are recorded in a database. Results: A total of 23 institutions, which are about 38% of the rheumatologic departments at tertiary academic hospitals across South Korea, are part of KORONA. The quality control of data collection and management has been performed through annual monitoring and auditing, staff training, and providing standard operation protocol by the executive committee of CRCRA. As of 31 December 2010, 4721 patients with established RA were included in KORONA, because an annual survey had started to be performed in July 2010. Conclusions: KORONA is the first nationwide Korean RA-specific cohort and it will provide valuable “real-world” information for Korean RA patients. [Copyright &y& Elsevier]

Background and Aims: This study was designed to identify susceptibility to insulin resistance and the association of serum resistin and adiponectin with insulin resistance in patients with Behçet''s disease (BD). Also, we identify risk determinants for insulin resistance in BD patients. Methods: The study population consisted of 82 BD patients (n = 26 males) and 89 healthy controls (n = 40 males). Clinical data were collected at the time of enrollment, and serum resistin and adiponectin levels were measured using enzyme-linked immunosorbent assays. The homeostasis model assessment of insulin resistance (HOMA-IR) was calculated by measuring fasting plasma glucose and insulin levels. Results: BD patients and healthy controls differed significantly in insulin resistance (HOMA-IR) (1.3 ± 1.1 vs. 0.7 ± 0.5, p <0.001) and serum resistin level (7901.7 ± 1314.9 vs. 7444.2 ± 1841.6, p = 0.001) but not in serum adiponectin level (p = 0.223). No differences in HOMA-IR, serum adiponectin, and serum resisitin were found between patients with active and inactive BD. It is determined that plasma glucose, plasma insulin, and serum resistin may be determinant for the HOMA-IR. The number of metabolic syndrome components is closely correlated with HOMA-IR in BD patients (r = 0.245, p = 0.029). Conclusion: This study demonstrates that there is an increased susceptibility to insulin resistance in patients with BD as compared to healthy controls. Serum resistin level may be an independent determinant for insulin resistance in BD patients. [Copyright &y& Elsevier]

Abstract: Background: Combined tramadol/acetaminophen is used to treat pain related to osteoarthritis. However, adverse events (AEs) leading to discontinuation can occur. Dose titration may decrease the risk for AEs. Objective: The aim of this study was to assess the effect of tramadol/acetaminophen titration on the development of AEs leading to treatment discontinuation in patients with knee osteoarthritis. Methods: This 2-week, multicenter, randomized, double-blind, double-dummy, add-on study was conducted at 12 tertiary referral university hospitals in the Republic of Korea. Patients aged 35 to 75 years with knee osteoarthritis receiving a stable dose of NSAIDs and with a daily mean pain-intensity score of ≥4 on a numeric rating scale (NRS) (0 = no pain to 10 = worst pain) during the 48 hours prior to enrollment were eligible. Patients were randomly assigned to receive 1 tablet of tramadol/acetaminophen 37.5/325 mg QD and 1 placebo BID for 3 days, followed by 1 active tablet BID and 1 placebo QD for 4 days, followed by 1 active tablet TID for 7 days (titration group) or 1 tablet of combined tramadol 37.5 mg/acetaminophen 325 mg TID for 14 days (nontitration group). The primary outcome measure was the rate of treatment discontinuation due to AEs. Secondary outcome measures were time to discontinuation due to AEs, prevalences and characteristics of AEs, decrease from baseline in pain intensity as measured on the NRS, and change in the Korean version of the Western Ontario and McMaster Universities (K-WOMAC) index score (scale: 0 = best to 100 = worst). Results: A total of 250 patients were enrolled (92.0% female; mean [SD] age, 60.2 [7.8] years; mean [SD] weight, 60.0 [9.2] kg [range, 37.5-90.7 kg]; all Korean). The discontinuation rate was significantly lower in the titration group than in the nontitration group (10.5% vs 26.2%; P < 0.001). The Kaplan-Meier survival curve showed that the rates of discontinuation due to AEs were similar in the 2 groups up to day 2, but thereafter the discontinuation rate was significantly lower in the titration group. The most common AEs were nausea (12.1% and 24.6% in the titration and nontitration groups, respectively; P = 0.008), vomiting (4.0% and 17.2%; P < 0.001), and dizziness (9.7% and 22.1%; P = 0.005). No serious AEs were reported in either group. Tramadol/acetaminophen use was associated with a similar decrease from baseline in pain in both the titration and nontitration groups (mean [SD] Δ: NRS, -1.60 [1.62] vs -1.68 [1.58]; total K-WOMAC, -12.86 [13.73] vs -12.52 [16.58]). Conclusions: In this population of Korean patients with knee osteoarthritis pain managed with a stable dose of NSAIDs, titration of tramadol/acetaminophen over 12 days was associated with improved tolerability and a significantly lower discontinuation rate compared with nontitration. Both regimens significantly reduced from baseline associated with osteoarthritis. [Copyright &y& Elsevier]

Abstract: Objective: To dissect the mechanism of the protection of staurosporin-induced apoptosis on rat chondrocytes by a purified extract from Clematis mandshurica. Design: Primary cultured rat articular chondrocytes as well as RCJ3.1C.18 cells were incubated with 1μM staurosporin and 300μg/ml purified extract from Clematis mandshurica. Western blot assay, silencing 14-3-3 gene and immunoprecipitation were conducted. Results: Clematis mandshurica prevented staurosporin-induced downregulation of several antiapoptotic bcl-2 family proteins Bcl-xL and Bcl-2, and staurosporin-induced upregulation of an apoptotic bcl-2 family protein Bax. Clematis mandshurica also prevented staurosporin-induced downregulation of a premitochondrial antiapoptotic protein 14-3-3. It is noticeable that siRNA to 14-3-3 abolished the prevention of caspase-3 activation by Clematis mandshurica. Furthermore viability assay corroborated that silencing of 14-3-3 gene abolished this apoptosis protection efficacy by Clematis mandshurica. Immunoprecipitation assay elucidated that Clematis mandshurica prevented the staurosporin-induced reduction of the interactions between 14-3-3 with phospho-ser112-Bad and Bcl-xL to phospho-ser155-Bad. Conclusions: Clematis mandshurica prevents staurosporin-induced apoptosis of rat chondrocytes via 14-3-3. [Copyright &y& Elsevier]