bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adalimumab Improves Sleep and Sleep Quality in Patients with Active Ankylosing Spondylitis
Authors: RUDWALEIT MARTIN , GOOCH KATHERINE , MICHEL BEAT , HEROLD MANFRED , THÖRNER ÅKE , WONG ROBERT , KRON MARTINA , CHEN NAIJUN , KUPPER HARTMUT 
Published: October 2010

Objective.Fatigue and sleep problems are significant in patients with ankylosing spondylitis (AS). This subanalysis of the RHAPSODY study (Review of Safety and Effectiveness with Adalimumab in Patients with Active Ankylosing Spondylitis) was conducted to evaluate the effect of adalimumab on sleep in patients with active AS.Methods.All patients (n = 1250) had active AS and received adalimumab 40 mg every other week during the 12-week open-label treatment period. Sleep was assessed by the Medical Outcomes Study Sleep Scale (MOS-SS) at screening and Weeks 6, 12, and 20 (optional continuation period). Effect sizes were calculated to determine clinical significance. Paired Student t tests compared the change in the MOS-SS domains from Week 12 to baseline. Correlation coefficients were calculated to determine the relationship between change in sleep domains and other Week 12 clinical and patient-reported outcomes (Bath AS Disease Activity Index, C-reactive protein, nocturnal pain, total back pain, Bath AS Functional Index, patient’s global assessment of disease activity, morning stiffness, Short Form-36 Health Survey, and Work Productivity and Activity Impairment questionnaire components).Results.At Week 12, adalimumab significantly improved sleep in each of the MOS-SS domains (p < 0.001). Effect sizes for 3 of the 6 domains (disturbance, −0.69; adequacy, 0.55; somnolence, −0.52) and both sleep problems indices (Index I, −0.68; Index II, −0.77) were moderate, suggesting clinical significance. Change in the MOS-SS Sleep Problem Index II was moderately correlated with change in most clinical and patient-reported outcomes. Sleep improvements were similar in patients with and without radiographically advanced AS.Conclusion.Adalimumab improves overall sleep and sleep quality in patients with active AS.
Relative Clinical Influence of Clinical, Laboratory, and Radiological Investigations in Early Arthritis on the Diagnosis of Rheumatoid Arthritis. Data from the French Early Arthritis Cohort ESPOIR
Authors: GOSSEC LAURE , COMBESCURE CHRISTOPHE , RINCHEVAL NATHALIE , SARAUX ALAIN , COMBE BERNARD , DOUGADOS MAXIME 
Published: October 2010

Objective.To evaluate the relative level of influence of usual investigations in early arthritis on the diagnosis of rheumatoid arthritis (RA).Methods.Patients: those included in the ESPOIR early arthritis cohort, a national cohort of patients with grade ≥ 2 synovitis for > 6 weeks and < 6 months. The diagnostic properties of variables assessed at baseline were measured against the diagnosis of RA defined by American College of Rheumatology criteria (at any timepoint between inclusion and 12-month followup) and expert opinion. Various models, including (1) clinical data; (2) clinical + radiographic data (plain radiographs); (3) addition of rheumatoid factor (RF) and/or anti-cyclic citrullinated peptide (anti-CCP); and (4) addition of HLA-DR typing, were assessed by comparing areas under the curves for ROC curves.Results.Of 731 patients studied, 372 (50.9%) satisfied criteria for RA at 1 year. In univariate analysis, sensitivity was highest for distal articular presentation (94.6%), presence of IgM RF (69.4%), pain on metatarso-phalangeal squeeze test (66.1%), and presence of anti-CCP (65.6%); whereas specificity was highest for nodules (100%), HLA typing: shared-epitope double dose (95.9%), radiographic erosions (86.5%), and anti-CCP antibodies (86.4%). The most efficient model included swollen joint count, morning stiffness, erosions, RF, and anti-CCP. Adding rheumatoid nodules, C-reactive protein, or HLA-DR information was not contributive.Conclusion.In addition to the clinical variables and radiographs, RF and/or anti-CCP are the single variables of interest that are contributive for the diagnosis of RA.
Cytokines and Regulatory T Cells in Rheumatoid Arthritis and Their Relationship with Response to Corticosteroids
Authors: de PAZ BANESA , ALPERI-LÓPEZ MERCEDES , BALLINA-GARCÍA FRANCISCO J. , PRADO CATUXA , GUTIÉRREZ CARMEN , SUÁREZ ANA 
Published: October 2010

Objective.To analyze circulating cytokines and regulatory T cells (Treg) in patients with rheumatoid arthritis (RA) of different durations, and their association with functional interleukin 10 (IL-10) and tumor necrosis factor-α (TNF-α) genotypes in patients treated with corticosteroids.Methods.Serum levels of IL-6, IL-10, IL-17, IL-18, TNF-α, and transforming growth factor-ß (TGF-ß) were quantified in 196 patients and 61 healthy controls. Percentage of CD4+CD25high cells was determined by flow cytometry and Foxp3 expression by real-time reverse-transcription polymerase chain reaction. Data were related to clinical measurements and presence of the genotype −1082GG IL-10/−308GG TNF-α, previously associated with good response to corticosteroids.Results.Levels of TNF-α, IL-6, and IL-18 were significantly higher in patients compared to controls, while TGF-ß and IL-10 were lower. Serum samples of patients at disease onset (n = 32) had increased IL-6 and decreased TGF-ß, but there were no differences in other cytokines. These patients also presented a higher percentage of CD4+CD25high cells than those with established disease, although no significant differences were detected in Foxp3. Patients under corticosteroid treatment who were carriers of the good responder genotype had higher levels of TGF-ß, Foxp3, and Treg compared to patients with other genotypes, while relatively lower levels of TNF-α and IL-17 were observed.Conclusion.Patients at onset of RA present fewer alterations in cytokine levels and Treg than those with longer disease duration, supporting the role of disease progression in subsequent changes. The antiinflammatory balance observed in high IL-10/low TNF-α patients treated with prednisone supports the use of these genetic polymorphisms as predictors of response to corticosteroid therapy.
An Audit of Behcet’s Syndrome Research: A 10-year Survey
Authors: ESEN FEHIM , SCHIMMEL ELIZABETH K. , YAZICI HASAN , YAZICI YUSUF 
Published: October 2010

Objective.Data suggest that the use of disease control groups and proper use of power calculations were neglected in published reports. We surveyed these and other methodological shortcomings in reports published within the last decade about one specific topic, Behcet’s syndrome. We reason that recognizing such methodological shortcomings will lead to better quality clinical and basic science articles.Methods.Articles published in the 15 highest impact factor journals on rheumatology, ophthalmology, dermatology, and general medicine between January 1999 and January 2009 were searched for original reports on Behcet’s syndrome. Study designs (study types and time element), control groups, demographic data, use of power calculations, and reporting of negative results were specifically tabulated.Results.Most studies on Behcet’s syndrome were cross-sectional (83%). Prospective longitudinal studies were few (7%). In a considerable proportion of papers (21%), some basic demographic data were missing. Power calculations were rare (3%) even in randomized controlled trials and were not considered at all in clinical hypothesis-testing. Disease control groups were present in slightly over half of clinical and laboratory original research, while just 13% of genetic association studies included disease controls. Only 12% of all reports concerned mainly negative outcomes.Conclusion.A considerable number of the published research articles have methodological weaknesses. The generalizability of what we observed in Behcet’s syndrome to other research topics needs to be formally studied.
Increased Prevalence of Metabolic Syndrome Associated with Rheumatoid Arthritis in Patients without Clinical Cardiovascular Disease
Authors: CROWSON CYNTHIA S. , MYASOEDOVA ELENA , DAVIS JOHN M. , MATTESON ERIC L. , ROGER VERONIQUE L. , THERNEAU TERRY M. , FITZ-GIBBON PATRICK , RODEHEFFER RICHARD J. , GABRIEL SHERINE E. 
Published: October 2010

Objective.To examine whether patients with rheumatoid arthritis (RA) with no overt cardiovascular disease (CVD) have a higher prevalence of metabolic syndrome (MetS) than subjects without RA or CVD. We also examined whether RA disease characteristics are associated with the presence of MetS in RA patients without CVD.Methods.Subjects from a population-based cohort of patients who fulfilled 1987 American College of Rheumatology criteria for RA between January 1, 1980, and December 31, 2007, were compared to non-RA subjects from the same population. All subjects with any history of CVD were excluded. Waist circumference, body mass index (BMI), and blood pressure were measured during the study visit. Data on CVD, lipids, and glucose measures were ascertained from medical records. MetS was defined using NCEP/ATP III criteria. Differences between the 2 cohorts were examined using logistic regression models adjusted for age and sex.Results.The study included 232 RA subjects without CVD and 1241 non-RA subjects without CVD. RA patients were significantly more likely to have increased waist circumference and elevated blood pressure than non-RA subjects, even though BMI was similar in both groups. Significantly more RA patients were classified as having MetS. In RA patients, MetS was associated with Health Assessment Questionnaire Disability Index, large-joint swelling, and uric acid levels, but not with C-reactive protein or RA therapies.Conclusion.Among subjects with no history of CVD, patients with RA are more likely to have MetS than non-RA subjects. MetS in patients with RA was associated with some measures of disease activity.
Rheumatoid Arthritis Disease-modifying Antirheumatic Drug Intervention and Utilization Study: Safety and Etanercept Utilization Analyses from the RADIUS 1 and RADIUS 2 Registries
Authors: GIBOFSKY ALLAN , PALMER WILLIAM R. , KEYSTONE EDWARD C. , SCHIFF MICHAEL H. , FENG JINGYUAN , McCROSKERY PETER , BAUMGARTNER SCOTT W. , MARKENSON JOSEPH A. 
Published: October 2010

Objective.To report the rates of serious adverse events (SAE), serious infectious events (SIE), and events of medical interest (EMI) in patients receiving etanercept; to identify the risk factors for SAE, SIE, and EMI; and to report time to switching from etanercept therapy, reasons for switching, and time to restarting treatment with etanercept in patients with rheumatoid arthritis (RA) in US clinical practice.Methods.Adults ≥ 18 years of age who fulfilled the 1987 American Rheumatism Association criteria for RA were eligible for enrollment in 2 prospective, 5-year, multicenter, observational registries. RADIUS 1 (Rheumatoid Arthritis DMARD Intervention and Utilization Study) enrolled patients with RA who required a change in treatment [either an addition or a switch of a biologic or nonbiologic disease-modifying antirheumatic drug (DMARD)]. In RADIUS 2, patients with RA were required to start etanercept therapy at entry. Patients were seen at a frequency determined by their rheumatologist. RADIUS 1 and RADIUS 2 were registered under the US National Institutes of Health ClinicalTrials.gov identifiers NCT00116714 and NCT00116727, respectively.Results.In these patients, SAE, SIE, and EMI occurred at rates comparable to those seen in clinical trials. No unexpected safety signals were observed. Rates for SAE, SIE, and EMI in etanercept-treated patients were comparable to rates observed in patients receiving methotrexate monotherapy and did not increase with greater exposure to etanercept therapy.Conclusion.The RADIUS registries provide a better understanding of the safety of etanercept in patients with RA in the US practice setting.
Is It Necessary to Combine Detection of Anticitrullinated Protein Antibodies in the Diagnosis of Rheumatoid Arthritis?
Authors: ZHAO JINXIA , LIU XIANGYUAN , WANG ZHIMIN , LIU RUI , LI ZHANGUO 
Published: October 2010

Objective.Antibodies against citrulline-containing epitopes, such as antiperinuclear factor (APF), antikeratin antibodies (AKA), antifilaggrin antibodies, and anticyclic citrullinated peptide (anti-CCP) antibodies, are specific in rheumatoid arthritis (RA). Detection of APF, AKA, and anti-CCP has been widely used in clinical practice. However, studies on combined detection of these anti citrullinated protein antibodies (ACPA) in the significance of diagnosing RA have been limited. We aimed to detect APF, AKA, and anti-CCP antibodies and to evaluate the significance of combined detection of these ACPA in RA.Methods.A total of 551 patients with arthritic disorders, 304 with RA and 247 with other rheumatic diseases, were selected at the Department of Rheumatology and Immunology during the past 2 years. AKA and APF were tested by indirect immunofluorescence assay. Anti-CCP was detected using the second-generation ELISA kit.Results.The sensitivities of anti-CCP, AKA, and APF tests for RA were 76.2%, 43.4%, and 34.5%, respectively, while the specificities were 96.0%, 98.4%, and 99.6%. The combination of anti-CCP, AKA, and APF positivity had the highest specificity (100%), but it yielded a low sensitivity (28.3%). When 2 of the 3 ACPA were positive, the sensitivity and specificity were 48.4% and 99.2%, respectively. When either anti-CCP or AKA or APF was positive, sensitivity increased to 77.3%, but specificity decreased to 94.7%.Conclusion.Anti-CCP was the most valuable marker in the diagnosis of RA, among the 3 ACPA. Combined detection of anti-CCP, AKA, and APF did not increase the diagnostic capability for RA.
Whole-blood Gene Expression Profiling in Ankylosing Spondylitis Shows Upregulation of Toll-like Receptor 4 and 5
Authors: ASSASSI SHERVIN , REVEILLE JOHN D. , ARNETT FRANK C. , WEISMAN MICHAEL H. , WARD MICHAEL M. , AGARWAL SANDEEP K. , GOURH PRAVITT , BHULA JITEN , SHARIF ROOZBEH , SAMPAT KEERAN , MAYES MAUREEN D. , TAN FILEMON K. 
Published: October 2010

Objective.To identify differentially expressed genes in peripheral blood cells (PBC) of patients with ankylosing spondylitis (AS) relative to healthy controls and controls with systemic inflammation.Methods.We investigated PBC samples of 16 patients with AS and 14 matched controls, in addition to systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) samples utilizing Illumina Human Ref-8 BeadChips. Candidate genes were confirmed using quantitative PCR. Subsequently, these genes were also validated in a separate sample of 27 patients with AS [before and after anti-tumor necrosis factor (anti-TNF) treatment] and 27 matched controls.Results.We identified 83 differentially expressed transcripts between AS patients and controls. This gene list was filtered through the lists of differentially expressed transcripts in SLE and SSc, which resulted in identification of 52 uniquely dysregulated transcripts in AS. Many of the differentially expressed genes belonged to Toll-like receptor (TLR) and related pathways.TLR4andTLR5were the only dysregulated TLR subtypes among AS patients. We confirmed the overexpression ofTLR4andTLR5in AS patients in comparison to controls (p = 0.012 and p = 0.006, respectively) and SLE (p = 0.002, p = 0.008) using quantitative PCR in the same sample. Similarly,TLR4(p = 0.007) andTLR5(p = 0.012) were significantly upregulated among the AS patients before anti-TNF treatment in the confirmatory sample.TLR4(p = 0.002) andTLR5(p = 0.025) decreased significantly after anti-TNF treatment.Conclusion.PBC gene expression profiling in AS shows an upregulation ofTLR4andTLR5.This supports the importance of TLR subtypes in the pathogenesis of AS that are responsible for the immune response to Gram-negative bacteria.
Informing Response Criteria for Psoriatic Arthritis (PsA). II: Further Considerations and a Proposal — The PsA Joint Activity Index
Authors: GLADMAN DAFNA D. , TOM BRIAN D.M. , MEASE PHILIP J. , FAREWELL VERNON T. 
Published: October 2010

Objective.To develop a recommended measure of response for use in psoriatic arthritis (PsA) clinical trials and observational cohort studies reflecting joint involvement.Methods.Previously, we used data from phase III randomized placebo-controlled trials of anti-tumor necrosis factor (TNF) agents to determine models, based primarily on statistical considerations but with some clinical input when necessary, that best distinguish drug-treated from placebo-treated patients. For the same data, we examine response criteria currently used for PsA and logistic regression models based on the individual components of these response criteria. Comparison with our previously developed models, based primarily on statistical consideration, is made.Results.A simplified score, the PsA Joint Activity Index (PsAJAI), based on components of the ACR30, performed better than the ACR20 and PsARC, and comparable to our previously developed models. The PsAJAI is a weighted sum of 30% improvement in core measures with weights of 2 given to the joint count measure, the C-reactive protein laboratory measure, and the physician global assessment of disease activity measure. Weights of 1 should be given to the remaining 30% improvement measures including pain, patient global assessment of disease activity, and the Health Assessment Questionnaire.Conclusion.We recommend the PsAJAI be used as an outcome measure for assessing joint disease response in PsA clinical trials.
Prevalence of Vitamin D Insufficiency/Deficiency in Rheumatoid Arthritis and Associations with Disease Severity and Activity
Authors: KERR GAIL S. , SABAHI IRAJ , RICHARDS JOHN S. , CAPLAN LIRON , CANNON GRANT W. , REIMOLD ANDREAS , THIELE GEOFFREY M. , JOHNSON DANNETTE , MIKULS TED R. 
Published: October 2010

Objective.25-hydroxy-vitamin D (25-OH-D) insufficiency/deficiency is increasingly prevalent and has been associated with many chronic diseases, including rheumatoid arthritis (RA). Our purpose was to define the prevalence and associations of 25-OH-D insufficiency/deficiency in a cohort of US veterans with RA.Methods.Vitamin D status (25-OH-D) was assessed in patients with RA using radioimmunoassay on banked plasma collected at enrollment. Insufficiency was defined as concentrations < 30 ng/ml and deficiency as < 20 ng/ml. Associations of 25-OH-D insufficiency/deficiency with patient characteristics obtained at enrollment were examined using multivariate logistic regression, adjusting for age, sex, season of enrollment, and race.Results.Patients (850 men, 76% Caucasian) had a mean (SD) age of 64 (SD 11.3) years. The prevalences of 25-OH-D insufficiency and deficiency were 84% and 43%, respectively. After multivariate adjustment, both insufficiency and deficiency were more common with anti-cyclic citrullinated peptide antibody positivity and non-Caucasian race, and in the absence of vitamin D supplementation. 25-OH-D deficiency, but not insufficiency, was independently associated with higher tender joint counts and highly sensitive C-reactive protein levels.Conclusion.In a predominantly elderly, male RA population, 25-OH-D insufficiency was highly prevalent. With the increasing adverse health outcomes associated with hypovitaminosis D, screening and supplementation, particularly among minority, seropositive patients with RA, should be performed routinely.
Treatment with Tiludronic Acid Helps Reduce the Development of Experimental Osteoarthritis Lesions in Dogs with Anterior Cruciate Ligament Transection Followed by Reconstructive Surgery: A 1-Year Study with Quantitative Magnetic Resonance Imaging
Authors: PELLETIER JEAN-PIERRE , TRONCY ÉRIC , BERTAIM THIERRY , THIBAUD DOMINIQUE , GOULET ANNE-CHRISTINE , ABRAM FRANÇOIS , CARON JUDITH , BOILEAU CHRISTELLE , d’ANJOU MARC-ANDRÉ , MOREAU MAXIM , LUSSIER BERTRAND , MARTEL-PELLETIER JOHANNE 
Published: October 2010

Objective.To investigate over a 1-year period in dogs that underwent extracapsular stabilization surgery (ECS) following anterior cruciate ligament (ACL) transection: whether reconstructive surgery could prevent osteoarthritis (OA) progression and whether treatment with the bisphosphonate tiludronic acid (TA) could improve the chronic evolution of OA structural changes.Methods.ACL transection was performed on dogs on Day 0 and ECS on Day 28. Dogs were randomly divided into 2 groups: 15 received placebo and 16 were treated with TA (2 mg/kg subcutaneous injection) on Days 14, 28, 56, and 84. Magnetic resonance images were acquired on Days −10, 26, 91, 210, and 357, and cartilage volume was quantified. At sacrifice (Day 364), cartilage from femoral condyles and tibial plateaus was macroscopically and histologically evaluated. Expression levels of MMP-1, -3, -13, ADAMTS-4, -5, BMP-2, FGF-2, IGF-1, TGF-ß1, collagen type II, and aggrecan were determined using real-time RT-PCR.Results.The loss of cartilage volume observed after ACL transection stabilized following ECS. Thereafter, a gradual gain occurred, with the cartilage volume loss on the tibial plateaus reduced at Day 91 (p < 0.02) and Day 210 (p < 0.001) in the TA-treated dogs. At sacrifice, TA-treated dogs presented a reduction in the severity of macroscopic (p = 0.03 for plateaus) and histologic (p = 0.07 for plateaus) cartilage lesions, had a better preserved collagen network, and showed decreased MMP-13 (p = 0.04), MMP-1 and MMP-3 levels.Conclusion.Our findings indicate that in dogs with ACL transection, ECS greatly prevents development of cartilage volume loss. Treatment with TA provided an additional benefit of reducing the development of OA lesions.
Tocilizumab for Rheumatoid Arthritis: A Cochrane Systematic Review
Authors: SINGH JASVINDER A. , BEG SABA , LOPEZ-OLIVO MARIA ANGELES 
Published: October 2010

Objective.To compare the benefit and safety of tocilizumab to placebo in patients with rheumatoid arthritis (RA).Methods.We searched multiple databases for published randomized or controlled clinical trials comparing benefit and safety of tocilizumab to placebo, disease-modifying antirheumatic drugs (DMARD), or other biologics. For dichotomous outcomes, we calculated the relative risk, and for continuous outcomes, the mean difference.Results.Eight randomized controlled trials were included in this systematic review, with 3334 participants, 2233 treated with tocilizumab and 1101 controls. The US and Canadian approved dose of tocilizumab, 8 mg/kg every 4 weeks, was given to 1561 participants. In patients taking concomitant methotrexate, compared to placebo, patients treated with approved dose of tocilizumab were substantially and statistically significantly more likely than placebo to achieve the American College of Rheumatology 50 (absolute percentage, 38.8% vs 9.6%, respectively; RR 3.2, 95% CI 2.7, 3.7); Disease Activity Score remission (30.5% vs 2.7%; RR 8.7, 95% CI 6.3, 11.8); and a clinically meaningful decrease in Health Assessment Questionnaire (HAQ)/Modified HAQ scores (60.5% vs 34%; RR 1.8, 95% CI 1.6, 1.9). There were no substantive statistically significant differences in serious adverse effects (0.8% vs 0.7%; RR 1.2, 95% CI 0.8, 1.6) or withdrawals due to adverse events (4.9% vs 3.7%; RR 1.4, 95% CI 0.9, 2.1); however, tocilizumab-treated patients were significantly more likely to have any adverse event (74% vs 65%; RR 1.05, 95% CI 1.03, 1.07); elevation in the ratio of low-density lipoprotein to high-density lipoprotein cholesterol (HDL; 20% vs 12%; RR 1.7, 95% CI 1.2, 2.2); and increase in the ratio of total to HDL cholesterol (12% vs 7%; RR 1.7, 95% CI 1.2, 2.6); and they were less likely to withdraw from treatment for any reason (8.1% vs 14.9%; RR 0.6, 95% CI 0.5, 0.8).Conclusion.At the approved dose of 8 mg/kg every 4 weeks, tocilizumab in combination with methotrexate/DMARD is beneficial in decreasing RA disease activity and improving function. Tocilizumab treatment was associated with a significant increase in cholesterol levels and occurrence of any adverse event, but not serious adverse events. Larger safety studies are needed to address these safety concerns.