bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improvement in Health‐Related Quality of Life for Children With Juvenile Idiopathic Arthritis After Start of Treatment With Etanercept
Authors: Klotsche Jens , Minden Kirsten , Thon Angelika , Ganser Gerd , Urban Andreas , Horneff Gerd 
Published: August 2013

ObjectiveImprovement in health‐related quality of life (HRQOL) is an important therapy goal in the treatment of patients with juvenile idiopathic arthritis (JIA). We investigated the 12‐month course of HRQOL in patients with JIA after the start of therapy with etanercept and identified its determining factors.MethodsChildren with JIA were enrolled in the BiKer (Biologics in Pediatric Rheumatology) registry at the start of etanercept treatment. Children were prospectively followed in the first year of treatment and completed the Pediatric Quality of Life Inventory (PedsQL) at each occasion. The change in HRQOL was investigated by random‐effect regression models. The time‐varying variables pain and inactive disease were used for predicting the change in HRQOL. Inactive disease was defined by the Wallace et al criteria and pain was assessed on a visual analog scale (range 0–100).ResultsThe children (n = 61) had a mean age of 10.6 years and a mean disease duration of 3.4 years at the start of etanercept. The mean PedsQL total score was 75. The PedsQL total score increased at a rate of 2.8 units per month (P < 0.001) in the first 6 months of treatment, up to a level of 89.7. A low HRQOL score was significantly highly associated with the number of tender joints, functional restrictions, pain, disease activity, and the existence of a comorbid condition at baseline. Inactive disease and reduced pain predicted better HRQOL under etanercept treatment.ConclusionHRQOL was dramatically improved in children who started etanercept treatment. Inactive disease and lower pain were important predictors for improvement of HRQOL over time.
Utility of the Ultrasound Examination of the Hand and Wrist Joints in the Management of Established Rheumatoid Arthritis
Authors: Ceponis Arnoldas , Onishi Maika , Bluestein Harry G. , Kalunian Kenneth , Townsend Jeanne , Kavanaugh Arthur 
Published: August 2013

ObjectiveTo investigate the usefulness of point‐of‐care hand and wrist joint ultrasound (US) examination in patients with established rheumatoid arthritis (RA).MethodsFifty‐one RA patients were evaluated using clinical disease activity measures and gray‐scale and power Doppler (PD) US. Agreement between US and clinical findings and its impact on physicians' confidence and clinical decision were assessed.ResultsAgreement between intraarticular PD signal and joint swelling (JS) was moderate (82%; κ = 0.44). Agreement between PD signal and joint tenderness to palpation (TTP) was fair (75%; κ = 0.24). The greatest agreement between PD signal and clinical findings was seen in the 5th metacarpophalangeal (MCP) joint (96% JS, 88% TTP) and the poorest agreement was seen in the wrist (69% JS, 65% TTP) and 2nd (75% JS, 72% TTP) and 3rd (82% JS, 72% TTP) MCP joints. The presence of PD signal in nonswollen and/or nontender joints accounted for most of the disagreement in the wrists, while the opposite was true for the 2nd/3rd MCP joints. Agreement between sonographic synovial thickening and clinical findings was poor. Total sonographic synovial hypertrophy or PD score correlated significantly with physician‐recorded, but not patient‐recorded, clinical outcomes. US increased both physicians' confidence in their clinical decision (P < 0.0005, irrespective of Clinical Disease Activity Index score) and patients' confidence in physicians' medical decisions (88.4% of the cases). US modified biologic agent and/or disease‐modifying antirheumatic drug (DMARD) use in 7 individual cases, but it did not affect the overall treatment plan (P > 0.15) or DMARD (P < 0.062) or biologic agent (P > 1.0) use in this group of RA patients.ConclusionPD examination of the wrist and 2nd/3rd MCP joints might be feasible and clinically meaningful in evaluation of disease activity in patients with established RA. US examination of the hand/wrist joints in RA increases physicians' confidence in their clinical decision and can help to individualize DMARD and biologic agent use.
Survival and Predictors of Mortality in Systemic Sclerosis‐Associated Pulmonary Arterial Hypertension: Outcomes From the Pulmonary Hypertension Assessment and Recognition of Outcomes in Scleroderma Registry
Authors: Chung Lorinda , Domsic Robyn T. , Lingala Bharathi , Alkassab Firas , Bolster Marcy , Csuka M. E. , Derk Chris , Fischer Aryeh , Frech Tracy , Furst Daniel E. , Gomberg‐Maitland Mardi , Hinchcliff Monique , Hsu Vivien , Hummers Laura K. , Khanna Dinesh , Medsger Thomas A. , Molitor Jerry A. , Preston Ioana R. , Schiopu Elena , Shapiro Lee , Silver Richard , Simms Robert , Varga John , Gordon Jessica K. , Steen Virginia D. 
Published: August 2013

ObjectiveTo assess cumulative survival rates and identify independent predictors of mortality in patients with incident systemic sclerosis (SSc)–associated pulmonary arterial hypertension (PAH) who had undergone routine screening for PAH at SSc centers in the US.MethodsThe Pulmonary Hypertension Assessment and Recognition of Outcomes in Scleroderma registry is a prospective registry of SSc patients at high risk for PAH or with definite pulmonary hypertension diagnosed by right‐sided heart catheterization within 6 months of enrollment. Only patients with World Health Organization group I PAH (mean pulmonary artery pressure ≥25 mm Hg and pulmonary capillary wedge pressure ≤15 mm Hg without significant interstitial lung disease) were included in these analyses.ResultsIn total, 131 SSc patients with incident PAH were followed for a mean ± SD of 2.0 ± 1.4 years. The 1‐, 2‐, and 3‐year cumulative survival rates were 93%, 88%, and 75%, respectively. On multivariate analysis, age >60 years (hazard ratio [HR] 3.0, 95% confidence interval [95% CI] 1.1–8.4), male sex (HR 3.9, 95% CI 1.1–13.9), functional class (FC) IV status (HR 6.5, 95% CI 1.8–22.8), and diffusing capacity for carbon monoxide (DLco) <39% predicted (HR 4.2, 95% CI 1.3–13.8) were significant predictors of mortality.ConclusionThis is the largest study describing survival in patients with incident SSc‐associated PAH followed up at multiple SSc centers in the US who had undergone routine screening for PAH. The survival rates were better than those reported in other recently described SSc‐associated PAH cohorts. Severely reduced DLco and FC IV status at the time of PAH diagnosis portended a poor prognosis in these patients.
Lifetime Risk of Total Knee Replacement and Temporal Trends in Incidence by Health Care Setting, Socioeconomic Status, and Geographic Location
Authors: Bohensky Megan A. , Ackerman Ilana , DeSteiger Richard , Gorelik Alexandra , Brand Caroline A. 
Published: August 2013

ObjectiveTo estimate the lifetime risk of total knee replacement (TKR) and examine temporal trends in TKR incidence in the state of Victoria, Australia.MethodsWe performed a retrospective analysis of a population‐based longitudinal cohort of patients (ages ≥40 years) who received a primary TKR in Victoria from 1999–2008. Hospital separations and life tables were used to estimate lifetime risk. Temporal changes in TKR incidence were examined according to health care setting (public versus private), socioeconomic status (SES), and geographic location (regional versus metropolitan).ResultsThere were 43,570 incidents of primary TKRs identified over the study period. In 2008, the lifetime risk of surgery was 10.4% (95% confidence interval [95% CI] 10.13–10.64%) for men and 11.9% (95% CI 11.63–12.13%) for women. TKRs increased steadily over the study period in private hospitals (overall increase of 90%) with a smaller growth in procedure numbers for public hospitals (overall increase of 40%). From 2002–2003 onward, the low SES tertile showed a lower incidence of TKR compared to the middle and high SES groups, with incidence rates of 1.09 (95% CI 1.04–1.15), 1.22 (95% CI 1.17–1.28), and 1.20 (95% CI 1.16–1.25) per 1,000 population, respectively (based on 2007–2008 figures). Increased numbers of TKRs were also found to be occurring among people residing in regional areas of Victoria (from 1.12 [95% CI 1.04–1.31] to 1.84 [95% CI 1.72–2.02] per 1,000 population).ConclusionIncreases in lifetime risk of TKR were evident. Although improved access to TKR for those living in regional areas was observed, sustained disparities relating to health care setting and SES warrant further investigation.
Measurement Properties of the German Michigan Hand Outcomes Questionnaire in Patients With Trapeziometacarpal Osteoarthritis
Authors: Marks Miriam , Audigé Laurent , Herren Daniel B. , Schindele Stephan , Nelissen Rob G. H. H. , Vliet Vlieland Thea P. M. 
Published: August 2013

ObjectiveTo investigate the reliability, validity, and responsiveness of the Michigan Hand Outcomes Questionnaire (MHQ) in patients with trapeziometacarpal (TMC) joint osteoarthritis (OA).MethodsIn this prospective observational study, patients diagnosed with TMC joint OA who received either conservative or surgical treatment were included. At baseline and at 1 year following the beginning of treatment, we measured key pinch strength and the patients filled out the MHQ, the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire, and the Short Form 12 health survey. Patients also completed these questionnaires 2–11 days after the last study visit. In order to analyze the measurement properties of the MHQ, we calculated test–retest reliability (intraclass correlation coefficient [ICC]), internal consistency (Cronbach's alpha for the 6 subscales), construct validity (Pearson's correlation coefficient [r]), responsiveness (effect sizes), and the minimum important change (MIC).ResultsWe included 177 patients, of whom 109 were scheduled for surgery. The mean ± SD MHQ total score for surgical patients increased from 48 ± 14 at baseline to 75 ± 18 at 1 year (P ≤ 0.001). In contrast, no treatment effect was observed in the conservative group (P = 0.74). The MHQ total score showed excellent test–retest reliability (ICC 0.95) and correlated strongly with the DASH (r = −0.77). Internal consistency of the MHQ subscales ranged between 0.77 and 0.89. A large effect size of 1.7 was found for the surgical patients, with an MIC of 17 points.ConclusionThe MHQ demonstrated good reliability, validity, and responsiveness in patients with TMC joint OA and can be recommended as a suitable assessment instrument in this population.
Performance of the Assessment of Quality of Life Measure in People With Hip and Knee Joint Disease and Implications for Research and Clinical Use
Authors: Ackerman Ilana N. , Busija Lucy , Tacey Mark A. , Bohensky Megan A. , Ademi Zanfina , Brand Caroline A. , Liew Danny 
Published: August 2013

ObjectiveTo comprehensively evaluate the performance of the Assessment of Quality of Life (AQoL) instrument for measuring health‐related quality of life (HRQOL) in people with hip and knee joint disease (arthritis or osteoarthritis).MethodsData from 237 individuals were available for analysis from a national cross‐sectional, population‐based study of hip and knee joint disease in Australia. AQoL‐4D data were evaluated using Rasch analysis. A range of measurement properties was explored, including model and item fit, threshold ordering, differential item functioning, and targeting.ResultsGood overall fit of the AQoL with the Rasch model was demonstrated across a range of tests, supporting internal validity. Only 1 item (relating to hearing) showed evidence of misfit. Most AQoL items showed logical sequencing of response option categories, with threshold disordering evident for only 2 of the 12 items (items 4 and 9). Minor issues with potential clinical and research implications include limited options for reporting pain and some evidence of measurement bias between demographic subgroups (including age and sex). Participants' HRQOL was generally better than that represented by the AQoL items (mean ± SD for person abilities −2.15 ± 1.39, mean ± SD for item difficulties 0.00 ± 0.67), indicating ceiling effects that could impact the instrument's ability to detect HRQOL improvement in population‐based studies.ConclusionThe AQoL is a competent tool for assessing HRQOL in people with hip and knee joint disease, although researchers and clinicians should consider the caveats identified when selecting appropriate HRQOL measures for future outcome assessment involving this patient group.
Platinum‐Catalyzed Divergent Reactivity of α‐Hydroxyallenes: Synthesis of Dihydrofurans and α,β‐Unsaturated Ketones
Authors: Alcaide Benito , Almendros Pedro , Fernández Israel , Campo Teresa Martínez del , Naranjo Teresa 
Published: August 2013

Abstractα‐Allenols were catalytically transformed into dihydrofurans in the presence of platinum dichloride. Notably, using platinum dichloride along with silver triflate as the catalytic system, α,β‐unsaturated ketones were obtained. Therefore, the role of the silver salt may not just consist in the activation of the platinum precatalyst.magnified image
Brief Report: Anti–Tumor Necrosis Factor α Targets Protein Kinase B/c‐Akt–Induced Resistance of Effector Cells to Suppression in Juvenile Idiopathic Arthritis
Authors: Wehrens Ellen J. , Vastert Sebastiaan J. , Mijnheer Gerdien , Meerding Jenny , Klein Mark , Wulffraat Nico M. , Prakken Berent J. , van Wijk Femke 
Published: August 2013

ObjectiveTo determine whether therapeutic strategies that block interleukin‐6 (IL‐6) or tumor necrosis factor α (TNFα) can improve the responsiveness of Teff cells to suppression in patients with juvenile idiopathic arthritis (JIA).MethodsSynovial fluid mononuclear cells (SFMCs) from the inflamed joints of patients with JIA were cultured in the presence of etanercept or anti–IL‐6 in vitro, and protein kinase B (PKB)/c‐Akt activation and responsiveness to suppression were measured. In addition, the in vivo effects of TNFα blockade were investigated using peripheral blood mononuclear cells obtained from patients before and after the start of etanercept therapy.ResultsIn vitro treatment of SFMCs with anti–IL‐6 led to improved Treg cell–mediated suppression of cell proliferation in some but not all patients. Blocking TNFα with etanercept, however, clearly enhanced suppression, especially that of CD8+ T cells. In the presence of etanercept, PKB/c‐Akt activation of Teff cells was reduced, and cells became more susceptible to transforming growth factor β–mediated suppression, indicating that anti‐TNFα directly targets resistant Teff cells.ConclusionThis study is the first to show that anti‐TNFα targets the resistance of Teff cells to suppression, resulting in improved regulation of inflammatory effector cells.
Increased Intracellular Oxygen Radical Production in Neutrophils During Febrile Episodes of Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Cervical Adenitis Syndrome
Authors: Sundqvist Martina , Wekell Per , Osla Veronica , Bylund Johan , Christenson Karin , Sävman Karin , Foell Dirk , Cabral David A. , Fasth Anders , Berg Stefan , Brown Kelly L. , Karlsson Anna 
Published: August 2013

ObjectivePeriodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome is an autoinflammatory disease of unknown etiology that primarily affects preschool‐aged children. PFAPA syndrome is characterized by recurrent attacks of fever and symptoms of inflammation consistent with the disease acronym. Since autoinflammatory diseases are, by definition, mediated by cells of the innate immune system, the aim of this study was to evaluate the functional features of neutrophils, the most abundant innate immune cell in the circulation, in children with PFAPA syndrome.MethodsBlood polymorphonuclear leukocytes (PMNs), obtained from patients with PFAPA syndrome during both febrile and asymptomatic, afebrile phases of the disease, as well as from healthy children (afebrile controls) and children with fever and abdominal pain (febrile controls), were analyzed for 3 key neutrophil characteristics: 1) apoptosis (measured by annexin V/7‐aminoactinomycin D staining), 2) production of reactive oxygen species (ROS) (measured by luminol/isoluminol‐amplified chemiluminescence), and 3) priming status (measured as responsiveness to galectin‐3 and up‐regulation of CD11b).ResultsCompared to PMNs obtained from patients with PFAPA syndrome during an afebrile interval and those from febrile controls, PMNs obtained from patients during a PFAPA syndrome flare produced elevated levels of intracellular NADPH oxidase–derived ROS, had significantly diminished rates of spontaneous apoptosis, and displayed signatures of priming. In contrast, PMNs from afebrile patients with PFAPA syndrome had a significantly elevated rate of spontaneous apoptosis compared to PMNs from afebrile controls.ConclusionThese findings demonstrate that 3 key aspects of neutrophil innate immune function, namely, apoptosis, priming, and generation of an intracellular oxidative burst, are altered, most prominently during febrile attacks, in children with PFAPA syndrome.
Brief Report: A Regulatory Variant in CCR6 Is Associated With Susceptibility to Antitopoisomerase‐Positive Systemic Sclerosis
Authors: Koumakis Eugénie , Bouaziz Matthieu , Dieudé Philippe , Ruiz Barbara , Riemekasten Gabriella , Airo Paolo , Müller‐Nurasyid Martina , Cusi Daniele , Matucci‐Cerinic Marco , Melchers Inga , Salvi Erika , Strauch Konstantin , Peters Annette , Cuomo Giovanna , Hachulla Eric , Diot Elisabeth , Hunzelmann Nicolas , Caramaschi Paola , Riccieri Valeria , Distler Jörg H. W. , Tarner Ingo , Avouac Jérôme , Letenneur Luc , Amouyel Philippe , Lambert Jean‐Charles , Chiocchia Gilles , Boileau Catherine , Allanore Yannick 
Published: August 2013

ObjectiveRecognition of the well‐known pleiotropism of autoimmune genes supports the concept of a shared pathogenesis across autoimmune diseases such as rheumatoid arthritis (RA) and systemic sclerosis (SSc). Studies have reproducibly demonstrated an association between susceptibility to RA and polymorphisms of the CCR6 gene, a surface marker for Th17 cells, and the causal variant was recently identified. The present study was thus undertaken to investigate whether CCR6 polymorphisms could also be associated with susceptibility to SSc.MethodsTwelve tag single‐nucleotide polymorphisms (SNPs) of CCR6, including the known RA‐associated SNP rs3093023, were genotyped in a total of 2,411 SSc patients and 7,084 healthy individuals from 3 European populations (France, Italy, and Germany). Meta‐analyses of the data were performed to assess whether an association exists between CCR6 polymorphisms and susceptibility to SSc or its main subtypes. Direct sequencing of DNA was performed to ascertain whether the functional dinucleotide polymorphism of CCR6 previously identified in RA (CCR6DNP) was also present in SSc.ResultsCombined analyses revealed an association between the rs10946216 SNP and SSc susceptibility (odds ratio [OR] 1.13, 95% confidence interval [95% CI] 1.05–1.21, adjusted P [Padj] = 0.026). The rs3093023 A allele and rs10946216 T allele were in high linkage disequilibrium, and both were found to confer disease susceptibility in the antitopoisomerase‐positive subset of SSc patients (OR 1.27, 95% CI 1.13–1.42, Padj = 1.5 × 10−3 and OR 1.32, 95% CI 1.17–1.48, Padj = 9.0 × 10−5, respectively, relative to healthy controls). Direct sequencing of the DNA of 78 individuals supported the hypothesis that the regulatory dinucleotide CCR6DNP could be the causal variant in SSc.ConclusionThe results of this study establish CCR6 as a new susceptibility factor for antitopoisomerase‐positive SSc, as demonstrated in 3 European Caucasian populations, confirming the notion that SSc and RA could conceivably share autoimmune risk alleles. The results also suggest a potential role of the interleukin‐17 pathway in SSc.
9G4+ Autoantibodies Are an Important Source of Apoptotic Cell Reactivity Associated With High Levels of Disease Activity in Systemic Lupus Erythematosus
Authors: Jenks Scott A. , Palmer Elise M. , Marin Elides Y. , Hartson Louise , Chida Asiya Seema , Richardson Christopher , Sanz Ignacio 
Published: August 2013

ObjectiveTo determine the prevalence of anti–apoptotic cell (anti‐AC) antibodies with the 9G4 idiotype (9G4+) and the relationship between this and other known 9G4+ specificities and disease activity in patients with systemic lupus erythematosus (SLE).MethodsSerum samples from 60 SLE patients and 40 healthy donors were incubated with apoptotic Jurkat cells and assayed by flow cytometry for the binding of 9G4+ antibodies. The samples were also tested for 9G4+ reactivity against naive B cells and total IgG and IgM anti‐AC antibody reactivity.ResultsThe 9G4+ antibodies bound late ACs in sera from a majority of the SLE patients (60%) but in sera from only 2 healthy control subjects. Among samples with global IgM or IgG anti‐AC antibodies, those with 9G4+ anti‐AC antibodies predominated. Patients with high levels of 9G4+ anti‐AC antibodies were more likely to have active disease. This was the case even in patients with IgG anti‐AC antibodies or anti–double‐stranded DNA antibodies. Patients with lupus nephritis were also more likely to have 9G4+ anti‐AC antibodies. While 9G4+ reactivity to ACs often coincided with anti–B cell reactivity, some samples had distinct anti–AC or anti–B cell reactivity.ConclusionThe 9G4+ antibody represents a major species of anti‐AC antibody in SLE serum, and this autoreactivity is associated with disease activity. The anti‐AC reactivity of 9G4+ antibodies can be separated from the germline VH4–34–encoded anti–B cell autoreactivity. Our results indicate that ACs are an important antigenic source in SLE that positively selects B cells with intrinsic autoreactivity against other self antigens. This selection of 9G4+ B cells by ACs may represent an important step in disease progression.
Overlapping Structural and Functional Brain Changes in Patients With Long‐Term Exposure to Fibromyalgia Pain
Authors: Jensen Karin B. , Srinivasan Priti , Spaeth Rosa , Tan Ying , Kosek Eva , Petzke Frank , Carville Serena , Fransson Peter , Marcus Hanke , Williams Steven C. R. , Choy Ernest , Vitton Olivier , Gracely Richard , Ingvar Martin , Kong Jian 
Published: August 2013

ObjectiveThere is vast evidence to support the presence of brain aberrations in patients with fibromyalgia (FM), and it is possible that central plasticity is critical for the transition from acute to chronic pain. The aim of the present study was to investigate the relationship between brain structure and function in patients with FM.MethodsFunctional connectivity of the brain during application of intermittent pressure–pain stimuli and measures of brain structure were compared between 26 patients with FM and 13 age‐ and sex‐matched healthy controls. Magnetic resonance imaging (MRI) was performed to obtain high‐resolution anatomic images and functional MRI scans of the brain, which were used for measurements of pain‐evoked brain activity.ResultsFM patients displayed a distinct overlap between decreased cortical thickness, decreased brain volumes, and decreased functional regional coherence in the rostral anterior cingulate cortex. The morphometric changes were more pronounced with longer exposure to FM pain. In addition, there was evidence of an association between structural and functional changes in the mesolimbic areas of the brain and the severity of comorbid depression symptoms in FM patients.ConclusionThe combined integration of structural and functional measures allowed for a unique characterization of the impact of FM pain on the brain. These data may lead to the identification of early structural and functional brain alterations in response to pain, which could be used to develop markers for predicting the development of FM and other pain disorders.