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3,300 | 666 | Behçet's disease (BD), a chronic systemic vasculitis, has distinct geographical and ethnic variation. Data regarding the epidemiology of patients with BD in the U.S. are limited; therefore, we sought to describe BD patient characteristics and medication use in the U.S., and compared them with data from patients from endemic regions.
We conducted a cross-sectional study using data from the RISE registry (2014-2018). Patients aged ≥ 18 years with BD were included. Sociodemographic and treatment information was extracted. We compared patients from the RISE registry to data from other published studies of patients with BD from endemic areas.
One thousand three hundred twenty-three subjects with BD from the RISE registry were included. Mean age was 48.7 ± 16.3 years, female to male ratio was 3.8:1, and 66.7% were White. The most frequently used medications included glucocorticoids (67.6%) and colchicine (55.0%). Infliximab and adalimumab were the most used biologics (14.5% and 14.1%, respectively); 3.2% of patients used apremilast. The RISE registry had more women (79.3%), and patients were older compared to previously published BD studies from endemic areas. Methotrexate and TNFi were more commonly reported in RISE (21.8% and 29.4%) compared to studies from Egypt and Turkey. Colchicine, cyclosporine, and cyclophosphamide were more commonly used in cohorts from Egypt, Turkey, and Iran. | Findings from the largest BD dataset in the U.S. suggest that BD patients are predominantly female. Further research is needed to explore the reasons for the higher prevalence of BD among women in the U.S. and its possible impact on disease severity and management. |
3,301 | 7,115 | Psychological factors and physical and emotional distress are frequently identified in fibromyalgia (FM). Previous reports have explored the relationship between some of these variables and functional disability and emotional distress in the disease; however, additional links with other potential psychological factors are unknown. This study aimed to assess the association between psychological variables and functional disability and emotional distress in individuals with FM.
This prospective, cross-sectional cohort study included 251 FM patients aged over 18 years. Demographic and clinical characteristics and outcome measures were recorded for each participant. Multiple linear regression analysis was performed to identify associations between the psychological factors.
The findings suggest significant associations between psychological variables and physical impact and emotional distress (anxiety and depression) (all p-values < 0.0001). Positive and negative affect, mindfulness, and perceived injustice were strongly associated with the physical and emotional impact (all p-values < 0.05) in the sample. | The study provides useful insights into the domains of physical and emotional distress. The findings should be incorporated into personalised treatments aimed at reducing functional disability and improving quality of life in patients with fibromyalgia. |
3,302 | 13,132 | The effects of physical activity (PA) in disease prevention and therapy have well-known effects on lower-limb osteoarthritis (OA), decreasing pain and improving function.
We aimed to describe the level and factors affecting PA practices of people with knee OA.
Prospective epidemiological study.
In all, 548 people with knee OA were interviewed by use of self-administered anonymous questionnaires.
The main outcome was physical activity level evaluated by the International physical activity questionnaire (IPAQ) (short version). Secondary outcomes included sociodemographic and clinical data, comorbidities, and barriers to and facilitators of practicing regular PA evaluated by 24 specific elements.
The mean (SD) age of the study population was 67.6 (7.9) years; 73.9% were women and 30.9% had obesity (mean [SD] body mass index [BMI] 28.2 [5.7] kg/m2). Multi-joint OA affected 92% of the population, and 71.6% had comorbidities. The mean (SD) visual analog scale score for pain intensity was 4.5/10 (2.5), which was 51.4% better than the patient acceptable symptom state (PASS). The mean (SD) Western Ontario and McMaster Universities Osteoarthritis Index function score was 36.6/100 (20.7), which was 57.5% better than the PASS. In total, 67% of patients used analgesics, half of them at least once a week. According to the IPAQ, 42.6% of patients reported high, 38.6% moderate, and 18.8% low PA level; the median IPAQ total activity score was 2628 metabolic equivalent of task (MET)-min/week and time spent sitting was 257.1min/day. Only one third of participants received non-pharmacological treatment corresponding to the latest recommendations. Variables significantly related to inactive or minimally active PA levels were BMI (P=0.0294), sex (P=0.0008), and biomedical barriers, related to self-efficacy (P=0.0118). | The OA study population was less active, more sedentary, and had more comorbidities and more barriers to PA practice than the overall population. |
3,303 | 15,785 | Interstitial lung disease (ILD) is one of the most serious complications of rheumatoid arthritis (RA). In the present study, we aimed to assess the efficacy of abatacept (ABA) in patients with ILD associated to RA.
National multicenter, non-controlled, open-label registry study of RA patients with ILD treated with ABA.
63 patients (36 women) with RA-associated ILD undergoing ABA therapy were studied. The mean ± standard deviation age at the time of the study was 63.2 ± 9.8 years. The median duration of RA and ILD from diagnosis were 6.8 and 1 year, respectively. RA was seropositive in 55 patients (87.3%). In 15 (23.8%) of 63 patients the development of ILD was closely related to the administration of synthetic or biologic disease modifying anti-rheumatic drugs. After a follow-up of 9.4 ± 3.2 months, two-thirds of patients remained stable whereas one-quarter experienced improvement in the Modified Medical Research Council scale. At that time forced vital capacity remained stable in almost two-thirds of patents and improved in one out of five patients assessed. Also, diffusing capacity of the lung for carbon monoxide remained stable in almost two-thirds and showed improvement in a quarter of the patients assessed. At 12 months, 50% of the 22 patients in whom chest HRCT scan was performed due persistence of respiratory symptoms showed stabilization, 8 (36.4%) improvement and 3 worsening of the HRCT scan pattern. Eleven of 63 patients had to discontinue ABA, mainly due to adverse events. | ABA appears to be an effective in RA-associated ILD. |
3,304 | 66,939 | To assess the usefulness of pyridinoline (Pyr) and deoxypyridinoline (Dpyr), intermolecular crosslinks of collagen, as markers in the evaluation of arthritis, by studying their distribution in tissues from knee joints.
Joint tissues (cartilage, bone, synovium) were obtained during operation from 10 patients with osteoarthritis (OA) and 10 patients with rheumatoid arthritis (RA). Synovium was also obtained from 10 non-arthritic (NA) subjects. Hydroxyproline was measured in hydrolysed tissue samples and converted to an equivalent collagen content. The amounts of Pyr and Dpyr crosslinks measured in the hydrolysed samples using a fluorescence technique were expressed as mumol/mol of collagen.
Pyr and Dpyr were distributed in all three tissues, but in different amounts. The ratio of the contents of Pyr and (Pyr:Dpyr) was 50:1 in cartilage, 3:1 in bone, and 25:1 in synovium. OA cartilage had a greater Dpyr content than the RA cartilage, but there was no other significant difference in the contents of Pyr and Dpyr and the ratio Pyr:Dpyr in the joint tissues from patients with OA or RA. In synovium, there was no significant difference between the contents of Pyr and Dpyr and the Pyr:Dpyr ratio among OA, RA, and NA tissues. | Both Pyr and Dpyr were located in cartilage, bone, and synovium. A significant amount of Pyr and Dpyr in these joint tissues, especially in synovium, may contribute to the urinary excretion of those crosslinks that is observed in arthritis. |
3,305 | 25,500 | There is conflicting evidence regarding prognosis in patients with primary SS (pSS). The aim of this study was to estimate the rate, risk factors and causes of mortality in patients with pSS through a systematic review and meta-analysis.
Through a systematic review of multiple databases through October 2014, we identified cohort studies reporting relative risk (compared with standardized population), risk factors and causes of mortality in patients with pSS. We estimated summary risk ratios (RRs) with 95% CIs using random effects model.
We identified 10 studies with 7888 patients (91% females) with pSS, of whom 682 patients died over a median average follow-up of 9 years. The pooled standardized mortality ratio in patients with pSS was 1.38 (95% CI 0.94, 2.01). Leading causes of mortality were cardiovascular diseases, solid-organ and lymphoid malignancies and infections; however, it is unclear whether these observed causes were overrepresented in patients with pSS as compared with the general population. Risk factors associated with increased mortality were advanced age at diagnosis [RR 1.09 (95% CI 1.07, 1.12)], male sex [RR 2.18 (95% CI 1.45, 3.27)], parotid enlargement [RR 1.81 (95% CI 1.02, 3.21)], abnormal parotid scintigraphy [RR 2.96 (95% CI 1.36, 6.45)], extraglandular involvement [RR 1.77 (95% CI 1.06, 2.95)], vasculitis [RR 7.27 (95% CI 2.70, 19.57)], anti-SSB positivity [RR 1.45 (95% CI 1.03, 2.04)], low C3 [RR 2.14 (95% CI 1.38, 3.32)] and C4 [RR 3.08 (95% CI 2.14, 4.42)] and cryoglobulinaemia [RR 2.62 (95% CI 1.77, 3.90)]. | pSS is not associated with an increase in all-cause mortality as compared with the general population. However, a subset of patients with extraglandular involvement, vasculitis, hypocomplementaemia and cryoglobulinaemia may be at increased risk of mortality and require close follow-up. |
3,306 | 57,213 | To investigate the role of the superficial zone in regulating the frictional response of articular cartilage. This zone contains the superficial protein (SZP), a proteoglycan synthesized exclusively by superficial zone chondrocytes and implicated in reducing the friction coefficient of cartilage.
Unconfined compression creep tests with sliding of cartilage against glass in saline were carried out on fresh bovine cylindrical plugs (slashed circle Ø6 mm, n=35) obtained from 16 bovine shoulder joints (ages 1-3 months). In the first two experiments, friction tests were carried out before and after removal of the superficial zone ( approximately 100 microm), in a control and treatment group, using two different applied load magnitudes (4.4 N and 22.2 N). In the third experiment, friction tests were conducted on intact surfaces and the corresponding microtomed deep zone of the same specimen.
In all tests the friction coefficient exhibited a transient response, increasing from a minimum value (mu(min)) to a near-equilibrium final value (micro(eq)). No statistical change (P>0.5) was found in micro(min) before and after removal of the superficial zone in both experiments 1 and 2. However, micro(eq) was observed to decrease significantly (P<0.001) after removal of the surface zone. Results from the third experiment confirm that micro(eq) is even lower at the deep zone. Surface roughness measurements with atomic force microscopy (AFM) revealed an increase in surface roughness after microtoming. Immunohistochemical staining confirmed the presence of SZP in intact specimens and its removal in microtomed specimens. | The topmost ( approximately 100 microm) superficial zone of articular cartilage does not have special properties which enhances its frictional response. |
3,307 | 14,757 | To investigate mortality and its predictors in a retrospectively defined population-based rheumatoid arthritis (RA) inception cohort Method: We included patients ascertained with incident RA from a region in the southern part of Denmark from 1995 to 2002. All patients fulfilled the 1987 American College of Rheumatology criteria for RA. The patients were followed from RA classification until death, emigration, or end of follow-up on 31 December 2013. We used personal record linkage with national public registers to obtain information on education, employment, cohabitation, comorbidity, and vital status.
The cohort comprised 509 patients, of whom 200 (39%) died during 6079 person-years. The most frequent underlying causes of death were cardiovascular disease (34%), neoplasms (26%), and respiratory disease (12%). In rheumatoid factor (RF)-positive males, the standardized mortality ratio (95% confidence interval) from all causes was 1.47 (1.15-1.88), from cardiovascular disease 1.63 (1.09-2.46), from respiratory disease 2.03 (1.06-3.90), and from neoplasms 2.26 (1.02-5.03) in the age group < 70 years, and 2.45 (1.23-4.90) in the age group > 79 years. On applying Cox models after multiple imputations by chained equations, we found that RF modified the effect of age. Employment status, comorbidity, and gender were independent baseline predictors of subsequent mortality. | In this cohort, significant excess mortality was confined to RF-positive males. The effect of age was modified by RF, and employment status and comorbidity were independent predictors of mortality. |
3,308 | 11,206 | This study aimed to investigate the diagnostic values of serum IL-10 and IL-17 in rheumatoid arthritis (RA) and their correlation with serum protein.
A retrospective analysis was performed on 116 RA patients admitted to the Yantaishan Hospital (the RA group) and 116 healthy subjects (the control group). Enzyme-linked immunosorbent assay was used to detect the expression levels of serum interleukin (IL)-10, IL-17 and 14-3-3η protein. Pearson analysis was performed to analyze the correlation between the expression levels of serum IL-10, IL-17 and 14-3-3η protein of patients in the RA group, and ROC curve analysis was conducted to measure the diagnostic values of IL-10, IL-17 and their combination in RA.
Patients in the RA group had significantly lower serum IL-10 level and markedly higher IL-17 and 14-3-3η protein levels than those in the control group (p<0.001). Serum IL-10 level was negatively correlated with 14-3-3η protein level in RA patients (r=-0.582, p<0.001). Serum IL-17 level was positively correlated with 14-3-3η protein level in RA patients (r=0.482, p<0.001). Serum IL-10 level was negatively correlated with IL-17 level in RA patients (r=-0.468, p<0.001). The AUC of IL-10 for diagnosing RA was 0.671, with a 95% confidence interval of 0.602-0.741 and a cut-off value of 87.315. The AUC of IL-17 for diagnosing RA was 0.856, with a 95% confidence interval of 0.807-0.905 and a cut-off value of 87.844. The AUC of IL-10 combined with IL-17 for diagnosing RA was 0.887. | RA patients had remarkably lower serum IL-10 level and significantly higher IL-17 and 14-3-3η protein levels than healthy people. IL-17 has better sensitivity and specificity than IL-10 for diagnosing RA. IL-10 combined with IL-17 is beneficial to improve the diagnostic level of RA, which provides the reference for the diagnosis, treatment and pathogenesis of RA. |
3,309 | 54,259 | Anti-TNFalpha has occasionally been used in the treatment of recalcitrant forms of systemic vasculitis such as Behçet's disease, Wegener's granulomatosis and Churg-Strauss syndrome. We report on the outcome of treatment in rheumatoid arthritis patients with cutaneous vasculitis lesions on anti-TNFalpha.
Two patients with rheumatoid arthritis present for several years had necrotic ulcers of the lower limbs due to cutaneous vasculitis. After the failure of various immunosuppressive drugs (cyclophosphamide, azathioprine, methotrexate), the two patients were treated with anti-TNFalpha: infliximab in the first case and adalimumab in the second. Cutaneous ulcers healed within two to four months of the start of anti-TNFalpha treatment. Despite ongoing anti-TNFalpha treatment, these cutaneous ulcers relapsed four to six months after complete healing. | Initially spectacular healing of cutaneous vasculitis ulcers under anti-TNF alpha treatment followed by relapse after several months of treatment is suggestive of an escape mechanism. |
3,310 | 25,941 | Osteoarthritis (OA) is a chronic joint disease, characterized by a progressive loss of articular cartilage. During OA, proinflammatory cytokines, such as interleukin IL-1, induce the expression of matrix metalloproteinases (MMPs) in chondrocytes, contributing thus to the extracellular matrix (ECM) degradation. Members of Serpine family, including plasminogen activator inhibitors have been reported to participate in ECM regulation. The aim of this study was to assess the expression of serpin peptidase inhibitor clade E member 2 (SERPINE2), under basal conditions and in response to increasing doses of IL-1α, in human cultured chondrocytes. We also examined the effects of SERPINE2 on IL-1α-induced MMP-13 expression. For completeness, the signaling pathway involved in this process was also explored.
SERPINE2 mRNA and protein expression were evaluated by RT-qPCR and western blot analysis in human T/C-28a2 cell line and human primary chondrocytes. These cells were treated with human recombinant SERPINE2, alone or in combination with IL-1α. ERK 1/2, NFκB and AP-1 activation were assessed by western blot analysis.
Human cultured chondrocytes express SERPINE2 in basal condition. This expression increased in response to IL-1α stimulation. In addition, recombinant SERPINE2 induced a clear inhibition of MMP-13 expression in IL-1α-stimulated chondrocytes. This inhibitory effect is likely regulated through a pathway involving ERK 1/2, NF-κB and AP-1. | Taken together, these data demonstrate that SERPINE2 might prevent cartilage catabolism by inhibiting the expression of MMP-13, one of the most relevant collagenases, involved in cartilage breakdown in OA. |
3,311 | 45,508 | To evaluate the intraobserver and interobserver reproducibility of B-mode and power Doppler (PD) sonography in patients with active long-standing rheumatoid arthritis (RA) comparatively with clinical data.
In each of 7 patients being considered for a change in their RA treatment regimen, 7 healthcare professionals examined the 28 joints used in the Disease Activity Score 28-joint count (DAS28). Then 7 sonographers examined each of the 7 patients twice, using previously published B-mode and PD grading systems. The clinical reference standard was presence of synovitis according to at least 4/7 examiners. The sonographic reference standard was at least grade 1 (ALG1) or 2 (ALG2) synovitis according to at least 4/7 sonographers. Interobserver reproducibility of sonography was assessed versus the sonographer having the best intraobserver reproducibility. Agreement was measured by Cohen's kappa statistic.
Intraobserver and interobserver reproducibility of B-mode and PD used separately was fair to good. Agreement between clinicians and sonographers at all sites using B-mode, PD, and both was 0.46, 0.37, and 0.36, respectively, for grade 1 synovitis; and 0.58, 0.19, and 0.19 for grade 2 synovitis. The number of joints with synovitis was smaller by physical examination (36.7%) than by B-mode with ALG1 (58.6%; p < 0.001). The number of joints with synovitis was higher by physical examination than by PD with both ALG1 (17.8%; p < 0.0001) and ALG2 (6.6%; p < 0.0001). | PD findings explain most of the difference between clinical and sonographic joint assessments for synovitis in patients with long-standing RA. |
3,312 | 44,572 | To examine the risk of diabetes mellitus (DM) among subjects with rheumatoid arthritis (RA), psoriatic arthritis or psoriasis (PsA/PsO), compared with non-rheumatic controls.
Study cohorts were assembled using linked healthcare utilisation data from British Columbia. All people with at least two diagnoses of RA or PsA/PsO were included and compared with a cohort of people without any known rheumatic disease. The outcome of interest was a diagnosis of new-onset DM, as defined by initiation of an antidiabetic drug. Incidence rates (IRs) per 1000 person-years and IR ratios were calculated and Cox regression models were constructed to determine the hazard ratio (HR) for diabetes by age, gender, systemic immunosuppressive drug and glucocorticoid use.
The study cohort comprised 48 718 subjects with RA, 40 346 with PsA/PsO and 442 033 without any rheumatic disease. The IR for DM among subjects with RA was 8.6 per 1000 person-years (95% CI 8.5 to 8.7), PsA/PsO 8.2 (95% CI 8.1 to 8.3) and for non-rheumatic controls 5.8 (95% CI 5.8 to 5.8). The adjusted HR for RA compared with non-rheumatic controls was 1.5 (95% CI 1.4 to 1.5) and 1.4 (95% CI 1.3 to 1.5) for PsA/PsO. | RA and PsA/PsO appear to be associated with an increased risk of DM. The ability of potent antirheumatic treatments to reverse this trend warrants study. |
3,313 | 60,927 | To study the prevalence of Sjögren's syndrome (SS), tear and saliva production and sicca symptoms in patients with inflammatory bowel disease (IBD) seen six years after IBD diagnosis.
In a population based cohort of 654 patients with IBD, 521 patients (80%) and a control group consisting of 68 healthy subjects were investigated. SS was diagnosed according to the European Criteria proposed by the American-European Consensus Group (US-EU criteria) and the European criteria. Maximum (supposing positive biopsies) and minimum prevalences (supposing negative biopsies) were estimated.
Dryness of eyes and mouth were similarly distributed between patients with ulcerative colitis (UC) and Crohn's disease (CD) and between patients and controls. The prevalence of SS was 0-4.2% and 0-5.7% (minimum-maximum) according to the US-EU criteria and the European criteria, respectively. The controls fulfilled neither of the criteria. | Sjögren's syndrome, sicca symptoms, tear and saliva production were not increased in patients with IBD compared to controls, indicating a lack of association between SS and IBD. |
3,314 | 21,752 | Hip osteoarthritis (OA) is the most common diagnosis in primary care adult patients presenting with hip pain but pain location and pain distribution in primary care patients with hip OA have been reported inadequately.
To describe pain location and pain distribution in primary care patients with clinical and radiographic confirmed hip OA.
Primary care patients with unilateral clinical and radiographic hip OA living on the island of Funen, Denmark were recruited from primary care to participate in a randomized clinical trial. At baseline, patients recorded pain intensity using an 11-box numeric rating scale and the distribution of hip pain using a manikin displaying three separate views: front, back and lateral. Pain drawings were analysed using a template to determine the most frequent pain locations and distribution of pain.
Pain drawings were completed by 109 patients of which 108 (99%) were valid. The mean age of patients was 65 (SD 9) years and 44% were females. The mean pain intensity was 5.4 (SD 2.0). A total of 77% had marked the greater trochanter area, 53% the groin area, 42% the anterior/lateral thigh area, 38% the buttock area, 17% the knee and 15% the lower leg area. No patients marked pain exclusively in the areas of the knee, posterior thigh or lower leg. | The most common pain locations of patients with hip OA presenting to primary care are the greater trochanter, groin, thigh and buttock areas. No patients recorded pain exclusively in the knee or lower leg. |
3,315 | 66,611 | To measure erythrocyte glutathione reductase (EGR) activity and riboflavin status, and their relations to disease activity, in rheumatoid arthritis patients compared to healthy controls.
Patients with rheumatoid arthritis were classified as active if there were features of articular inflammation which required initiation or change of disease modifying therapy, and as inactive if they had little evidence of articular inflammation. EGR was measured in patients and healthy controls by a functional assay with or without the addition of flavin adenine dinucleotide (FAD). The ratio of stimulated EGR (with FAD added) to basal EGR (no added FAD), which measures riboflavin status, is known as the EGR activation coefficient (EGRAC). An EGRAC > or = 1.3 represents biochemical riboflavin deficiency.
91 patients with rheumatoid arthritis, including 57 with active disease, and 220 healthy controls were studied. Both basal and stimulated EGR were significantly higher in patients with rheumatoid arthritis (P = 0.0001) than in controls. Biochemical riboflavin deficiency was identified in 41% controls and 33% patients with active rheumatoid arthritis but was significantly less frequent (9%) in patients with inactive compared to active disease (P = 0.02) or healthy controls (P = 0.0006). Pain score, articular index, C reactive protein, and erythrocyte sedimentation rate were increased in patients with riboflavin deficiency (all P < 0.02). | Higher basal and stimulated EGR might be expected in patients with rheumatoid arthritis in response to chronic oxidative stress due to synovial inflammation. The association of riboflavin deficiency with increased disease activity suggests that impaired EGR activity could facilitate continuing inflammation in these patients. |
3,316 | 30,025 | To describe fundamental movement skills (FMS), physical fitness and level of physical activity among Australian children with juvenile idiopathic arthritis (JIA) and compare this with healthy peers.
Children aged 6-16 years with JIA were recruited from hospital rheumatology clinics and private rheumatology rooms in Sydney, Australia. All children attended an assessment day, where FMS were assessed by a senior paediatric physiotherapist, physical fitness was assessed using the multistage 20-metre shuttle run test, and physical activity and physical and psychosocial well-being were assessed with questionnaires. These results were compared with age- and gender-matched peers from the NSW Schools Physical Activity and Nutrition Survey and the Health of Young Victorians Study using logistic regression analysis.
Twenty-eight children with JIA participated in this study. There were no differences in the proportion of children who had mastered FMS between children with JIA and their healthy peers (P > 0.05). However, there was a trend for children with JIA to have poorer physical fitness and be less physically active than healthy peers. Parents of children with JIA indicated more physical and psychosocial impairments among their children and themselves compared with parents of healthy children (P < 0.05). | This is the first study in Australia to compare FMS, physical activity and fitness in children with JIA and their peers. While older children with JIA appear to have poorer physical fitness and physical activity levels than their peers, there is no difference in FMS. |
3,317 | 23,943 | To investigate the contributions towards hyperuricaemia of known risk factors, focusing on fractional (renal) clearance of urate (FCU) and variation in the ATP-binding cassette transporter, sub-family G 2 (ABCG2) gene.
The contributions of age, sex, ancestry, Q141K genotype for ABCG2, FCU, sugar-sweetened beverage and alcohol consumption, metabolic syndrome disorders and measures of renal function to the risk of hyperuricaemia were evaluated by comparing hyperuricaemic (serum urate≥0.42 mmol/L, n=448) with normouricaemic (serum urate<0.42 mmol/L, n=344) participants using stepwise logistic regression. Model performance was evaluated using the area under the receiver operator characteristic curve (AUROC).
ABCG2 genotype, FCU, male sex, body mass index, serum triglyceride concentrations, estimated glomerular filtration rate and consumption of alcohol were the best predictors of hyperuricaemia (AUROC 0.90, 81% accuracy). Homozygosity in the 141K variant for ABCG2 conferred an adjusted OR of 10.5 for hyperuricaemia (95% CI 2.4 to 46.2). For each 1% decrease of FCU, the adjusted OR increased by 51% (OR 1.51, 95% CI 1.37 to 1.66). There was no association between ABCG2 genotype and FCU (r=0.02, p=0.83). | The ABCG2 141K variant and the FCU contribute strongly but independently to hyperuricaemia. These findings provide further evidence for a significant contribution of ABCG2 to extra-renal (gut) clearance of urate. |
3,318 | 25,091 | To validate a new method to identify responders (relative effect per patient (REPP) >0.2) using the OMERACT-OARSI criteria as gold standard in a large multicentre sample.
The REPP ([score before - after treatment]/score before treatment) was calculated for 845 patients of a large multicenter European cohort study for THR. The patients with a REPP >0.2 were defined as responders. The responder rate was compared to the gold standard (OMERACT-OARSI criteria) using receiver operator characteristic (ROC) curve analysis for sensitivity, specificity and percentage of appropriately classified patients.
With the criterion REPP>0.2 85.4% of the patients were classified as responders, applying the OARSI-OMERACT criteria 85.7%. The new method had 98.8% sensitivity, 94.2% specificity and 98.1% of the patients were correctly classified compared to the gold standard. | The external validation showed a high sensitivity and also specificity of a new criterion to identify a responder compared to the gold standard method. It is simple and has no uncertainties due to a single classification criterion. |
3,319 | 13,078 | Interleukin (IL)-37 has emerged as a novel anti-inflammatory cytokine that play an immunosuppressive role in regulating inflammatory response. This study aimed to measure IL-37 levels in the plasma and peripheral blood mononuclear cells (PBMCs) of patients with systemic juvenile idiopathic arthritis (sJIA), and to establish the correlation between IL-37 levels and disease activity, laboratory parameters and inflammatory cytokines.
The mRNA levels of IL-37 in PBMCs and plasma IL-37 concentrations in 46 sJIA patients and 30 age- and sex-matched healthy controls were measured by real-time polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. The correlations between plasma IL-37 levels and disease activity, laboratory parameters and inflammatory cytokines in sJIA were analyzed by Spearman correlation test. PBMCs from the sJIA patients were stimulated with recombinant human IL-37 (rhIL-37) protein, expressions of IL-1β, IL-6, TNF-α and IL-17 were detected by RT-PCR and ELISA.
Plasma levels of IL-37 and relative IL-37 mRNA expression were significantly elevated in sJIA patients, especially in active sJIA patients, when compared with the healthy controls (P < 0.001). Furthermore, patients with active disease showed higher IL-37 mRNAs and plasma protein levels than those with inactive disease as well as healthy controls. Plasma IL-37 levels were correlated with disease activity and inflammatory cytokines (IL-6, TNF-α, IL-17 and GM-CSF) in sJIA patients. The productions of inflammatory cytokines such as IL-6, TNF-α, IL-17 in PBMCs from sJIA patients were obviously decreased after recombinant IL-37 stimulation, whereas the production of IL-1β was not changed. | Our results demonstrate that levels of IL-37 were higher in sJIA patients, which were correlated with disease activity and sJIA related inflammatory cytokines. In addition, rhIL-37 down-regulates the expressions of inflammatory cytokines form PBMCs in sJIA patients, suggesting that IL-37 may have the potential role as a natural inhibitor for the pathogenesis and therapy of sJIA. |
3,320 | 12,817 | To assess the efficacy and safety of methotrexate (MTX) in combination with an approved biological agent compared to biological monotherapy, in the management of patients with rheumatoid arthritis (RA).
MEDLINE, EMBASE, CENTRAL and other sources were searched for randomised trials evaluating a biological agent plus MTX versus the same biological agent in monotherapy. Co-primary outcomes were ACR50 and the number of patients who discontinued due to adverse events (AEs). Random-effects models were applied for meta-analyses with risk ratio and 95% confidence intervals and the GRADE approach was used to assess confidence in the estimates.
The analysis comprised 16 trials (4965 patients), including all biological agents approved for RA except anakinra and certolizumab. The overall likelihood of responding to therapy (i.e. ACR50) after 6 months was 32% better when MTX was given concomitantly with biological agents (1.32 [1.20-1.45]; P < 0.001) corresponding to 11 more out of 100 patients (7-16 more); Moderate Quality Evidence. Discontinuing due to AEs from concomitant use of MTX was potentially 20% increased (1.21 [0.97-1.50]; P = 0.09) compared to biological monotherapy corresponding to 1 more out of 100 patients (0-3 more); Moderate Quality Evidence. | Randomised trials provide Moderate Quality Evidence for a favourable benefit-harm balance supporting concomitant use of MTX rather than monotherapy when prescribing a biological agent in patients with RA although in absolute terms only 7-16 more out of 100 patients will achieve an ACR50 response after 6 months of this combination therapy. |
3,321 | 43,945 | ABILHAND is a Rasch-built questionnaire that measures manual ability in rheumatoid arthritis (RA) patients. This study aimed to examine the test-retest reliability and the responsiveness of ABILHAND in RA patients.
Eighty-eight patients underwent 3 evaluations: the first evaluation was at baseline (time 1), the second was 2 weeks later (time 2), and the third was 1 year later (time 3). Disease activity was assessed using the Disease Activity Score in 28 joints using the C-reactive protein level (DAS28-CRP). Patients rated the intensity of their RA-related pain using a 100-mm visual analog scale for pain and completed questionnaires based on their activity limitations (ABILHAND and the Health Assessment Questionnaire) and quality of life.
The responsiveness analyses were conducted by using global, group, and individual approaches. The global approach showed significant differences between the time 1 and time 3 scores of the DAS28-CRP (P = 0.04) and ABILHAND (P = 0.04). Based on the changes in disease activity scores and the European League Against Rheumatism response criteria, the sample was divided into 3 groups: deteriorated, stable, and improved. The mean ± SD changes in manual ability were higher in the deteriorated (-1.23 ± 1.53 logit) and in the improved (1.22 ± 2.06 logits) groups than in the stable group (0.48 ± 1.09 logit). The effect size and standardized response mean confirmed that observation. The minimal clinically important difference was assessed in each group of patients. | The ABILHAND questionnaire exhibited responsiveness in detecting slight changes in RA patients. Therefore, the ABILHAND tool can be used to evaluate the functional status of RA patients in clinical trials and settings. |
3,322 | 24,423 | To evaluate the efficacy of switching the route from intravenous tocilizumab (TCZ) infusion (TCZ-IV) to subcutaneous TCZ injection (TCZ-SC) in a real-world setting through a comparison of the clinical response.
Fifty-eight rheumatoid arthritis (RA) patients, for whom TCZ-SC was initiated following TCZ-IV between June 2013 and August 2014, were consecutively enrolled. Disease activity score (DAS)28-ESR, simplified disease activity index (SDAI), and clinical disease activity index (CDAI) were examined at baseline and after switching from TCZ-IV to TCZ-SC for 3 months. We investigated whether body weight and body mass index (BMI) affected the efficacy of TCZ-SC.
Most of the patients had achieved remission or low disease activity at baseline (77.6% examined by DAS28). Fifty-seven patients (98%) continued the TCZ-SC treatment, and the disease activity was well controlled after 3 months. ΔDAS28 tended to be worsened after switching to TCZ-SC in the high-body-weight groups (≥60 kg) as compared with the groups with body weight <60 kg, although no statistical significance was found. BMI did not affect the efficacy of TCZ-SC. | Caution should be exercised in the high-body-weight subjects, but these data indicate that TCZ-SC maintains the favorable RA disease activity established using TCZ-IV. |
3,323 | 43,337 | To investigate and compare facial asymmetry in subjects with JIA with unilateral, bilateral or no TM joint (TMJ) involvement.
Eighty-one subjects with JIA: 22 with unilateral TMJ involvement (Group 1), 15 with bilateral TMJ involvement (Group 2) and 44 with no TMJ involvement (Group 3). Panoramic X-rays and three-dimensional (3D) photographs (surface scans) were obtained for all subjects. Panoramic X-rays were rated for severity of TMJ involvement. For each individual, a spatially detailed facial asymmetry map was created from the 3D photograph. Mean and variability of asymmetry were calculated for each of the three groups and compared.
Distinct patterns of asymmetry were found in Groups 1 and 2. With mean asymmetry values up to 3.5 mm, Group 1 exhibited a significantly greater amount of asymmetry in a broad band along the lower jaw extending from the region of the condyle to the chin than Group 2. The mean facial asymmetry (1 S.D.) for each JIA group was 2.3 (0.9), 2.0 (0.7), 1.7 (0.5) mm for Groups 1, 2 and 3, respectively. | JIA subjects with TMJ involvement displayed patterns of facial asymmetry consistent with the destruction of the condylar growth centre, leading to mandibular asymmetry with displacement of the bony chin. Facial asymmetry quantification was found to be an effective method for assessing both the amount and the localization and spatial extent of asymmetry in all 3Ds. |
3,324 | 58,800 | To investigate whether prolonged methotrexate (MTX) treatment after induction of remission influences the subsequent duration of remission in patients with juvenile idiopathic arthritis (JIA), and to analyse the usefulness of myeloid related proteins 8 and 14 (MRP8/MRP14) as predictive markers for the stability of remission at the time when MTX is withdrawn.
Twenty five patients with oligoarticular and polyarticular JIA who received MTX to induce remission were followed up. MTX treatment was stopped after a mean of 3.8 months (group 1) or 12.6 months (group 2) after remission was documented. Differences in the number of relapses between these groups were looked for. Additionally, MRP8/MRP14 were analysed by ELISA in 22 patients.
No difference was found in the number of relapses between patients with prolonged or early discontinued MTX treatment. Patients who were in stable remission had significantly lower MRP levels when MTX was discontinued than patients with relapses. With a cut off point for MRP8/MRP14 at 250 ng/ml, sensitivity and specificity were 100% and 70%, respectively. | Longer duration of MTX treatment after induction of remission does not generally improve the status of remission in patients with JIA. Residual synovial inflammation seems to influence the rate of relapses after discontinuation of MTX treatment. MRP8/MRP14 indicate residual activity even in the absence of other laboratory or clinical signs of continuing inflammation. Normal serum concentrations of MRP8/MRP14 in clinical inactive arthritis may help to identify patients in whom MTX can be safely withdrawn after remission is achieved. |
3,325 | 47,111 | To investigate the relationship between interleukin 17 (IL-17) producing T cells (Th17) and CD4+CD25+FOXP3+ regulatory T cells (Tregs) in blood and synovial fluid (SF) of patients with juvenile idiopathic arthritis (JIA).
Sixty-five children with JIA (18 males and 47 females, median age 6.2 yrs; 45 with oligoarticular and 20 with polyarticular course) and 75 age- and sex-matched healthy controls were studied. Flow cytometry was used to analyze the forkhead box P3 (FOXP3)-positive Treg cells in peripheral blood (PB) and synovial fluid mononuclear cells (SFMC). FOXP3 and retinoic-acid related orphan receptor C isoform 2 (RORC2) messenger RNA (mRNA) were assessed by real-time polymerase chain reaction analysis. Cytokines (IL-17 and Th1/Th2 related cytokines) were measured in culture supernatants of 11 paired PBMC and SFMC activated with PMA and ionomycin.
FOXP3+ T cells and FOXP3 mRNA amounts were significantly lower in PB of children with JIA as compared with controls (p = 0.0002 and p = 0.001, respectively) and a higher percentage of Treg cells with concomitant higher level of FOXP3 transcript levels were observed in SF when compared with their PB counterparts (both p < 0.0001). SF CD4+FOXP3+ T cells were characterized by higher amounts of FOXP3 protein per cell when compared with peripheral CD4+FOXP3+ T cells, as revealed by the difference in FOXP3 median fluorescence intensity (median +/- SD, arbitrary units, 54 +/- 22.6 vs 19.5 +/- 4.2; p < 0.001). RORC2 transcript levels were higher in JIA joints when compared with matched PB samples (median fold increase 3.9, p < 0.0001) but negatively correlated with FOXP3 mRNA levels (r = -0.623, p = 0.04). Stimulated SFMC displayed an impaired ability to produce IL-17 when compared with PBMC and, interestingly, an inverse relationship between IL-17 levels and the percentage of CD4+CD25+FOXP3+ SF T cells (r = -0.510, p = 0.047) was seen. | We demonstrated for the first time an increased synovial expression of the transcription factor of Th17, RORC2, in JIA, and its inverse relationship with FOXP3 mRNA. These results extend research on "Th17" and Tregs in JIA. |
3,326 | 31,144 | Nonspecific chronic synovitis of the knee joint was reported by Pollard in 1962 and its pathogenesis is considered to be a physiological reaction to intra-articular disease. In this study, we evaluated the pathological findings of the synovium of early osteoarthritis (OA)-affected knee joints with hydrarthrosis in comparison to typical OA.
Synovial tissues were harvested from early OA knee joints with hydrarthrosis graded 0-2 according to the Kellgren and Lawrence classification and examined by histopathology.
The synovial tissues showed proliferation of fibroblast-like synoviocytes (FLS) as if in rheumatoid arthritis (RA), and were immunohistochemically positive for matrix metalloproteinase 3, tumor necrosis factor α and interleukin 6. | The histology of RA is characterized by marked proliferation of FLS. In this study, the synovial tissues of early OA with hydrarthrosis showed moderate FLS proliferation. They also expressed the cytokines that are detected in the synovial tissues of RA. We suggest long-term follow-up is needed because early OA with hydrarthrosis might progress to overt RA. |
3,327 | 10,862 | Patients suffering from multiple functional somatic syndromes (FSS) such as fibromyalgia, chronic fatigue syndrome, or irritable bowel syndrome, often lack both a clear diagnosis and tangible illness explanations, which is a barrier for treatment engagement. We tested a short-term intervention taking the unifying concept of Bodily Distress Syndrome (BDS) as a point of departure. The intervention consisted of a clinical assessment, group-based patient education, and one follow-up consultation.
174 patients were included and received questionnaires at baseline, after clinical assessment, after patient education, and median 19 weeks after baseline. Data were analyzed using random effects models and simple t-tests. Qualitative data were thematically analyzed.
We found small reductions in symptom levels, considerable reductions in illness worry, and improvement of illness perceptions and illness-related behaviors. Overall, patients evaluated the intervention positively and expressed high expectations for further treatment. Qualitative results mainly supported these findings.
Physicians in primary and secondary care should strive to give patients with multiple FSS a clear understanding that their various FSS diagnoses are related and provide tangible illness explanations. | Targeting illness perceptions through patient education is crucial to obtain patient engagement in self-help management or further treatment. This may lead to improved outcomes. |
3,328 | 64,331 | To develop components of a multidimensional Health Assessment Questionnaire (MDHAQ) through the addition of new items in the "patient-friendly" HAQ format, including advanced activities of daily living (ADL), designed to overcome "floor effects" of the HAQ and modified HAQ (MHAQ) in which patients may report normal scores although they experience meaningful functional limitations, and psychological items, designed to screen efficiently for psychological distress in routine care.
The new MDHAQ items, as well as scales for pain, fatigue, helplessness, and global health status on a 2-page questionnaire, were completed by 688 consecutive patients with various rheumatic diseases, including 162 with rheumatoid arthritis (RA), 114 with fibromyalgia, 63 with osteoarthritis, 34 with systemic lupus erythematosus, 20 with vasculitis, 18 with psoriatic arthritis, 16 with scleroderma, and 261 with various other rheumatic diseases, over 2 years at a weekly academic rheumatology clinic.
The new MDHAQ items have good test-retest reliability and face validity. MHAQ scores were highest in patients with RA, and scores for other scales were highest in patients with fibromyalgia. On the advanced ADL, 58% of patients reported difficulty with errands, 68% with climbing stairs, 79% with walking two miles, 87% with participating in sports and games, and 94% with running or jogging two miles. On the psychological items, 75% of patients reported difficulty with sleep, 63% with stress, 61% with anxiety, and 57% with depression. Normal MHAQ scores were reported by 23% of patients and normal HAQ scores by 16% of patients who completed these questionnaires, while fewer than 5% had normal scores on the MDHAQ. | The MDHAQ items overcome in large part the "floor effects" seen on the HAQ and MHAQ, and are useful to screen for problems with sleep, stress, anxiety, and depression in the "patient-friendly" HAQ format. These data support the value of completion of a simple 2-page patient questionnaire by each patient at each visit to a rheumatologist. |
3,329 | 9,627 | Intra-articular injection of adipose-derived stem cells (ASCs) has shown promise for improving symptoms and cartilage quality in the treatment of osteoarthritis (OA). However, while most preclinical studies have been performed with plastic-adherent ASCs, most clinical trials are being conducted with the stromal vascular fraction (SVF), prepared from adipose tissue without prior culture.
To directly compare clinical outcomes of intra-articular injection with ASCs or SVF in patients with knee OA.
Cohort study; Level of evidence, 3.
The authors retrospectively compared 6-month outcomes in 42 patients (59 knees) receiving intra-articular injection with 12.75 million ASCs and 38 patients (69 knees) receiving a 5-mL preparation of SVF. All patients had Kellgren-Lawrence grade 2, 3, or 4 knee OA and had failed standard medical therapy. The visual analog scale (VAS) pain score and Knee injury and Osteoarthritis Outcome Score (KOOS) at baseline and 1, 3, and 6 months after injection were considered as outcomes. Outcome Measures in Rheumatology-Osteoarthritis Research Society International (OMERACT-OARSI) criteria were also used to assess positive response. A repeated measures analysis of variance was used for comparison between the treatment groups.
No major complications occurred in either group. The SVF group had a higher frequency of knee effusion (SVF 8%, ASC 2%) and minor complications related to the fat harvest site (SVF 34%, ASC 5%). Both groups reported improvements in pain VAS and KOOS domains. Specifically, in the ASC group, symptoms improved earlier (by 3 months; | It was observed that both ASCs and SVF resulted in clinical improvement in patients with knee OA, but that ASCs outperform SVF in the early reduction of symptoms and pain with less comorbidity. |
3,330 | 25,814 | Indicators of work role functioning (being at work, and being productive while at work) are important outcomes for persons with arthritis. As the worker productivity working group at OMERACT (Outcome Measures in Rheumatology), we sought to provide an evidence base for consensus on standardized instruments to measure worker productivity [both absenteeism and at-work productivity (presenteeism) as well as critical contextual factors].
Literature reviews and primary studies were done and reported to the OMERACT 12 (2014) meeting to build the OMERACT Filter 2.0 evidence for worker productivity outcome measurement instruments. Contextual factor domains that could have an effect on scores on worker productivity instruments were identified by nominal group techniques, and strength of influence was further assessed by literature review.
At OMERACT 9 (2008), we identified 6 candidate measures of absenteeism, which received 94% endorsement at the plenary vote. At OMERACT 11 (2012) we received over the required minimum vote of 70% for endorsement of 2 at-work productivity loss measures. During OMERACT 12 (2014), out of 4 measures of at-work productivity loss, 3 (1 global; 2 multiitem) received support as having passed the OMERACT Filter with over 70% of the plenary vote. In addition, 3 contextual factor domains received a 95% vote to explore their validity as core contextual factors: nature of work, work accommodation, and workplace support. | Our current recommendations for at-work productivity loss measures are: WALS (Workplace Activity Limitations Scale), WLQ PDmod (Work Limitations Questionnaire with modified physical demands scale), WAI (Work Ability Index), WPS (Arthritis-specific Work Productivity Survey), and WPAI (Work Productivity and Activity Impairment Questionnaire). Our future research focus will shift to confirming core contextual factors to consider in the measurement of worker productivity. |
3,331 | 66,827 | To use lipopolysaccharide (LPS) to create synovitis in the midcarpal joint of ponies, and to assess the morphologic, histochemical, and immunohistochemical effects of synovitis on articular cartilage of the third carpal bone.
2- to 3-year-old ponies, 6 control (group 1) and 6 treated (group 2).
Synovitis was induced in 1 midcarpal joint of group-2 ponies by intra-articular injections of LPS (0.02 micrograms/kg of body weight), morphine (0.1 mg/kg), and saline solution (group 2a) and a morphine and saline solution alone in the contralateral midcarpal joint (group 2b). Articular cartilage sections and attached synovial membrane from the third carpal bones were examined by immunohistochemical distribution of interleukin 1 beta, tumor necrosis factor (TNF)-alpha, TNF receptors (P55, P75) and 3-B-3(-) epitopes, and by localization of proteoglycans (metachromatic staining). Proteoglycan extracts were assessed by metachromatic staining or western blotting and immunohistochemical staining, using anti-3-B- antibodies.
Enhanced immunoreactivity for the cytokines and receptors was found in inflamed synovial membrane and noncalcified cartilage (group 2a more than 2b). Metachromasia of the noncalcified cartilage was greater in group-1 than in group-2a and group-2b specimens. In group 2a, chondrocyte hypertrophy and enhanced immunoreactivity for 3-B-3(-) epitope in areas of increased cytokine immunoreactivity suggested possible phenotypic change of the chondrocytes in response to synovitis. Immunohistochemical analysis by western blotting of proteoglycan extracts indicated strong 3-B-3(-) epitope immunolocalization in group-2a, weaker staining in group-2b, and barely detectable stain in group-1 specimens, which correlated with in situ immunolocalization. | Intra-articular administration of LPS may be used to induce a synovial environment conductive to increased immunoreactivity of interleukin 1 beta, TNF-alpha, and its receptors in equine synovial membrane and articular cartilage. These cytokines may be involved in the early phenotypic change of chondrocytes that is believed to occur in osteoarthritis and is characterized in this study by enhanced 3-B-3(-) epitope immunoreactivity and chondrocyte hypertrophy. |
3,332 | 49,904 | A chronic inflammation leads to joints deformations, which in consequence results in disability and decrease in quality of life. In the 1960s, the evaluation of the treatment of patients with chronic disease started to include quality of life.
to evaluate quality of life in patients with rheumatoid arthritis (RA) on the basis of chosen questionnaires; to determine the usefulness of chosen questionnaires in assessing quality of life of patients suffering from rheumatoid arthritis; to investigate whether quality of life of patients with rheumatoid arthritis depends on radiological and functional stage of disease, its duration, their age, sex and activity of the disease.
The study involved RA patients treated in the Department ofRheumatology and Rheumatologic Outpatient Clinic SPSK-1 in Szczecin. Patients' quality of life was evaluated with following questionnaires: Medical Outcomes Study 36-Item Short Form (SF-36), the Health Assessment Questionnaire (HAQ) and Arthritis Impact Measurement Scale (AIMS). The quality and understanding of all scales were tested with Cronbach test for reliability. The results were statistically analyzed using Spearman test, the chi2 test or the chi2 test with Yates' correction, Kruskal-Wallis test and analysis of variance and covariance. The study group consisted of 155 RA patients (117 females and 38 males). No significant differences were found between males and females in age and in degree of radiological changes.
The value of alpha-Cronbach's reliability factor accounted 0.99, 0.93, 0.81 in AIMS, HAQ and SF-36 questionnaires respectively. There were significant correlations between questionnaires and their scales, particularly in regard to physical fitness. The correlation between HAQ score and AIMS Physical Functioning scales in total and SF Physical Functioning accounted 0.78 and 0.67 (p < 0.001) respectively. No differences in evaluation of quality of life between men and women were found. No correlation was found between both the duration of RA and the age of patients and the activity of the disease as measured with DAS 28 indicator; correlation coefficient accounted 0.07 (p = 0.39) and 0.11 (p = 0.16) respectively. However, older subjects with longer duration of a disease and more active inflammatory process assessed their quality of life as poorer (correlation coefficient between DAS 28 and HAQ, AIMS Physical Functioning scales in total, SF-36 Physical Functioning accounted = 0.44, 0.43, -0.41 respectively; p = 0.0000. In addition, the radiological and functional stage of disease influenced essentially the assessment of the quality of life in examined group. | 1. The questionnaires used in the study: HAQ, AIMS and SF-36 were highly useful and they mutually correlated significantly in assessing quality of life of patients suffering from rheumatoid arthritis. 2. High mutual correlation of the questionnaires assessing Quality of Life of RA patients, that was found in the study, indicates, that each of them could be interchangeably used in everyday medical practice. 3. Quality of life of rheumatoid arthritis patients depends on: radiological and functional stage of the disease, its duration and activity. |
3,333 | 28,259 | Hyperuricemia and gout are associated with an increased risk of cardiovascular disease (CVD). It is unknown whether treating hyperuricemia with xanthine oxidase inhibitors (XOIs), including allopurinol and febuxostat, modifies cardiovascular risks.
We used US insurance claims data to conduct a cohort study among gout patients, comparing XOI initiators with non-users with hyperuricemia defined as serum uric acid level ≥6.8 mg/dL. We calculated incidence rates of a composite nonfatal cardiovascular outcome that included myocardial infarction, coronary revascularization, stroke, and heart failure. Propensity score (PS)-matched Cox proportional hazards regression compared the risk of composite cardiovascular endpoint in XOI initiators vs those with untreated hyperuricemia, controlling for baseline confounders. In a subgroup of patients with uric acid levels available, PS-matched Cox regression further adjusted for baseline uric acid levels.
There were 24,108 PS-matched pairs with a mean age of 51 years and 88% male. The incidence rate per 1000 person-years for composite CVD was 24.1 (95% confidence interval [CI] 22.6-26.0) in XOI initiators and 21.4 (95% CI, 19.8-23.2) in the untreated hyperuricemia group. The PS-matched hazard ratio for composite CVD was 1.16 (95% CI, 0.99-1.34) in XOI initiators vs those with untreated hyperuricemia. In subgroup analyses, the PS-matched hazard ratio for composite CVD adjusted for serum uric acid levels was 1.10 (95% CI, 0.74-1.64) among XOI initiators. | Among patients with gout, initiation of XOI was not associated with an increased or decreased cardiovascular risk compared with those with untreated hyperuricemia. Subgroup analyses adjusting for baseline uric acid levels also showed no association between XOI and cardiovascular risk. |
3,334 | 64,411 | Synovial inflammation in patients with rheumatoid arthritis (RA) is characterised by the presence of large numbers of highly activated monocytes and macrophages. The importance of these cells in the aethiopathogenesis and prognosis of RA is increasingly recognised. The object of this report is to determine whether monocytes and monocyte derived macrophages of RA patients produce increased cytokine mRNA levels.
Monocyte derived macrophages from RA patients and healthy controls were cultured either in the absence or presence of lipopolysaccharide. The expression levels of the mRNAs encoding GAPDH, interleukin 1beta (IL1beta), IL8, and alpha(2) macroglobulin in these cells were analysed by reverse transcriptase-polymerase chain reaction (RT-PCR).
Activated monocyte derived macrophages from RA patients produce significantly higher IL8 mRNA levels than activated macrophages from healthy controls. By contrast, resting RA and control macrophages produce similar levels of IL8 mRNA. Culturing of activated macrophages in the presence of RA or control sera has no effect on the expression levels of IL8 mRNA. No significant differences between RA and control macrophages were observed in the expression levels of IL1beta and alpha(2) macroglobulin mRNAs. | These data indicate that the increased IL8 mRNA production capacity of RA macrophages upon activation is an intrinsic property of these cells, and is not attributable to factors present in the circulation. Based on these observations, it is postulated that this innate hyper-responsiveness of RA macrophages contributes to the high IL8 levels present in the synovial fluid of rheumatoid joints, and is implicated in the chemotactic gradient leading to the homing of leucocytes to the joints. |
3,335 | 52,066 | The aim of this study was to investigate potential risk factors for Sjögren's syndrome (SS) by means of a multi-centre case-control study, focusing in particular on familial and environmental risk factors. 140 female SS patients and 109 female controls with orthopaedic problems were consecutively enrolled in seven university hospitals in Italy.
Information regarding the patient's lifestyle, her medical, menstrual and pregnancy history, and any family history of autoimmune diseases (AD) was obtained through a detailed structured questionnaire. The odds ratio (OR) and 95% confidence interval (95%CI) were calculated using unconditional logistic regression, adjusting for age and family size. The probability of first-degree relatives developing an autoimmune disease was also investigated.
A positive family history of AD was significantly associated with SS. Subjects with a first-degree relative (FDR) with AD showed a seven-fold increase in the risk for SS compared to controls (OR=7.4, 95%CI 2.8-20.1); the strength of this association increased with the number of relatives affected. Similarly, the FDR of SS patients had a higher risk of AD in comparison to subjects without FDR affected by SS. Women with one or more pregnancies had an increased risk of SS (OR=2.1, 95%CI 1.0-4.3). | This study suggests that a family history of AD is associated with SS. |
3,336 | 11,999 | Anti-cyclic citrullinated peptide 2 antibodies (anti-CCP2) and rheumatoid factor (RF) in rheumatoid arthritis (RA) has been extensively assessed in industrialized countries. We investigated the diagnostic and prognostic impact of anti-CCP2 and RF isotypes in a Sudanese cross-sectional RA cohort.
Consecutive RA patients (n = 281) diagnosed according to the 1987 ACR criteria were included 2008-2010. Anti-CCP2 and RF isotypes (IgA, IgM, and IgG) were measured by enzyme immunoassay in 262 patients, with reference intervals aligned to the same diagnostic specificity as for anti-CCP2 (97.6%) using national controls.
IgA RF was the predominant RA-associated autoantibody (56%), followed by IgM RF and anti-CCP2 (both 52%) and IgG RF (49%). In receiver operator characteristic analysis, IgA RF also showed the largest area under the curve. Patients with IgG RF were younger and had 8 years lower median age of disease onset compared to antibody negative patients (p < 0.0001). IgG RF was the only marker associated with a high number of involved joints (p = 0.028), and together with anti-CCP2 were the strongest markers for finger deformities (p = 0.016 and p = 0.012), respectively. No statistical differences were found for disease duration, ESR and Hb levels, and occurrence of erosions/osteopenia for any of the investigated autoantibodies. | Whereas IgA RF showed the best diagnostic performance, IgG RF associated with low age of RA onset, high number of involved joints, and finger deformities. These findings indicate that RA-associated antibodies other than conventional IgM RF and anti-CCP2 might be informative in non-Caucasian RA populations. |
3,337 | 31,799 | The aim of this study was to investigate antidepressant use in a nationwide cohort of persons with incident rheumatoid arthritis (RA) in 2000-2007 in Finland.
Register data from the Social Insurance Institution of Finland were used to evaluate antidepressant use in ≥ 50-year-old incident RA patients (n = 10,356) and the same-age general population.
Of the RA patients, 10.0% (n = 1034) had used antidepressants during the year preceding RA diagnosis. The cumulative incidence of antidepressant initiations after RA diagnosis was 11.4% [95% confidence interval (CI) 10.0-12.9] for men and 16.2% (95% CI 14.9-17.5) for women at the end of follow-up (mean 4.4 years). Female gender [age-adjusted hazard ratio (HR) 1.39, 95% CI 1.21-1.60] and increasing number of comorbidities (p for linearity < 0.001) predicted antidepressant initiations. In the last follow-up year, antidepressant use was at the same level among men with RA [prevalence rate ratio (PRR) 0.93, 95% CI 0.82-1.06] but lower among women (PRR 0.89, 95% CI 0.83-0.95) when compared to the general population. | Antidepressant initiations in early RA were associated with female gender and comorbidity. Although depression is stated to be a sizeable problem in RA, the prevalence of antidepressant use did not exceed the population level. |
3,338 | 8,114 | Treatment of rheumatoid arthritis with rituximab (RTX) requires repeated cycles, but there is no well-established retreatment regimen in dose and frequency. The objective was to analyse the persistence of RTX treatment and factors that influence in terms of routine clinical practice.
Rituximab in Rheumatoid Arthritis (RITAR Study) is an observational, retrospective study that analyses the persistence of RTX in a cohort from 2003 to 2015. Persistence was calculated by the Kaplan-Meier analysis; curves were compared with the Log-Rank test. Cox regression was used to quantify the risk of discontinuation and multivariate analyses were conducted to determine the factors associated with the persistence of the treatment.
454 cycles of RTX in 114 patients were included. Median survival was 10.0 years and incidence rate of discontinuation was 7.7 per 100 patients/year. Factors associated with persistence were autoantibody positivity and use of RTX in combination with csDMARDs. Sex, age, number of comorbidities, rheumatoid arthritis evolution, number of complications, basal DAS28, basal HAQ, number of lines of treatment, fixed or on demand retreatment and year of RTX starting were not associated. Multivariable models confirmed the relationship between autoantibody positivity, monotherapy and persistence of RTX. | The persistence of RTX in clinical practice is higher in seropositive patients and in those who are treated with RTX associated with a csDMARD. Dose per cycle and retreatment frequency do not have a decisive role in rituximab persistence. |
3,339 | 36,481 | Our aim was to determine the effects of infliximab on bone mineral metabolism in rheumatoid arthritis (RA) patients and analyze the relationship between inflammatory markers of acute phase thought to play a major role in bone remodeling.
36 patients with established RA were investigated. All patients underwent physical examination and blood and urinary analysis at baseline, 2 weeks, 14 weeks, 6 months and 12 months after the initiation of treatment. The serum levels of: tumor necrosis factor alpha (TNF-alpha), tumor necrosis factor alpha receptor 1 (TNFR1), TNFR2, interleukin 6 (IL-6), IL-17, IL-23 and markers of bone remodeling such as osteocalcin (BGP), deoxypyridynoline (Dpd), and N-telopeptide of type I collagen (NTx) were measured by ELISA.
The results showed significant decrease of all the above cytokines levels in RA patients in comparison with those after 2 weeks of treatment. After 6 months, the markers of bone formation and resorption decreased compared to baseline values. We found positive correlation between the levels of NTx and the levels of IL-6, IL-17 and TNFR1, and between the levels of Dpd and IL-6 and Dpd and TNFR2, whereas negative correlation between BGP and IL-23. After 12 months the positive association was found at the BGP level and IL-6 as well as Dpd and the level of IL-6. We also observed a positive relation between Dpd and TNF-alpha and negative between BGP and TNFR1. | We suggest that infliximab treatment may limit the risk of osteoporosis in RA patients. |
3,340 | 42,727 | To develop a simplified and relatively inexpensive version of cartilage proteoglycan-induced arthritis (PGIA), an autoimmunity model of rheumatoid arthritis (RA), and to evaluate the extent to which this new model replicates the disease parameters of PGIA and RA.
Recombinant human G1 domain of human cartilage PG containing "arthritogenic" T cell epitopes was generated in a mammalian expression system and used for immunization of BALB/c mice. The development and progression of arthritis in recombinant human PG G1-immunized mice (designated recombinant human PG G1-induced arthritis [GIA]) was monitored, and disease parameters were compared with those in the parent PGIA model.
GIA strongly resembled PGIA, although the clinical symptoms and immune responses in mice with GIA were more uniform than in those with PGIA. Mice with GIA showed evidence of stronger Th1 and Th17 polarization than those with PGIA, and anti-mouse PG autoantibodies were produced in different isotype ratios in the 2 models. Rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies were detected in both models; however, serum levels of IgG-RF and anti-CCP antibodies were different in GIA and PGIA, and both parameters correlated better with disease severity in GIA than in PGIA. | GIA is a novel model of seropositive RA that exhibits all of the characteristics of PGIA. Although the clinical phenotypes are similar, GIA and PGIA are characterized by different autoantibody profiles, and the 2 models may represent 2 subtypes of seropositive RA, in which more than 1 type of autoantibody can be used to monitor disease severity and response to treatment. |
3,341 | 30,184 | The effect of ultra-long distance running on the ankle cartilage with regard to biochemical changes, thickness and lesions is examined in the progress of a transcontinental ultramarathon over 4486 km.
In an observational field study, repeated follow-up scanning of 22 participants of the TransEurope FootRace (TEFR) with a 1.5 T MRI mounted on a mobile unit was performed. For quantitative biochemical and structural evaluation of cartilage a fast low angle shot (FLASH) T2* weighted gradient-echo (GRE)-, a turbo-inversion-recovery-magnitude (TIRM)- and a fat-saturated proton density (PD)-weighted sequence were utilized. Statistical analysis of cartilage T2* and thickness changes was obtained on the 13 finishers (12 male, mean age 45.4 years, BMI 23.5 kg/m²). None of the nine non-finisher (eight male, mean age 53.8 years, BMI 23.4 kg/m²) stopped the race due to ankle problems.
From a mean of 17.0 ms for tibial plafond and 18.0 ms for talar dome articular cartilage at baseline, nearly all observed regions of interest (ROIs) of the ankle joint cartilage showed a significant T2*-signal increase (25.6% in mean), with standard error ranging from 19% to 33% within the first 2500 km of the ultra-marathon. This initial signal behavior was followed by a signal decrease. This signal recovery (30.6% of initial increase) showed a large effect size. No significant morphological or cartilage thickness changes (at baseline 2.9 mm) were observed. | After initial T2*-increase during the first 2000-2500 km, a subsequent T2*-decrease indicates the ability of the normal cartilage matrix to partially regenerate under ongoing multistage ultramarathon burden in the ankle joints. |
3,342 | 24,014 | Patients with rheumatoid arthritis (RA) suffer from co-morbidities that contribute to a shortened lifespan. Inflammation is important for the development of cardiovascular disease, but little is known on its relationship with other co-morbidities. We investigated the role of inflammation for the development of new comorbidities in early RA.
Since 1995, all patients with early RA in Northern Sweden are included in a prospective study on co-morbidities, with a total of 950 patients being included. At the time for this study, 726 had been ill for ≥5 years. Data on co-morbidities, clinical and laboratory disease activity and pharmacological therapy were collected from patient records and further validated using a questionnaire at RA onset (T0) and after 5 years (T5).
Of the patients, 53.2 % of the patients had one or more co-morbidity at onset, the commonest being: hypertension (27.3 %), obstructive pulmonary disease (13.9 %), diabetes (8.0 %), hypothyroidism (6.3 %) and malignancy (5.0 %). After 5 years, 41.0 % had developed at least one new co-morbidity, the most common being: hypertension (15.1 %), malignancy (7.6 %), stroke/transient ischemic accident (5.1 %), myocardial infarction (4.3 %) and osteoporosis (3.7 %). Age at disease onset, a raised erythrocyte sedimentation rate (ESR) at inclusion, previous treatment with glucocorticoids (GC; p < 0.001 for all), extra-articular RA (Ex-RA; p < 0.01), DAS28 (area under the curve) at 24 months (p < 0.05), previous smoking at inclusion (p = 0.058) and male gender (p < 0.01) were associated with a new co-morbidity overall at T5. Treatment with biologics (p < 0.05) reduced the risk. In multiple logistic regression modelling, ESR (p = 0.036) at inclusion was associated with a new co-morbidity after 5 years, adjusted for age, sex, smoking and GC treatment. In a similar model, Ex-RA (p < 0.05) was associated with a new co-morbidity at T5. In a third model, adjusted for age and sex, a new pulmonary co-morbidity was associated with a smoking history at inclusion (p < 0.01), but not with ESR. | There was substantial co-morbidity among early RA patients already at disease onset, with considerable new co-morbidity being added during the first five years. Measures of disease activity were associated with the occurrence of a new co-morbidity indicating that the inflammation is of importance in this context. |
3,343 | 67,943 | The aim of this controlled endoscopic study was to compare the therapeutic efficacy and the gastric tolerance of two nonsteroidal anti-inflammatory drugs, pirprofen versus naproxen.
A randomized endoscopic double-blind double-dummy study.
The gastrointestinal unit of a teaching hospital.
Forty patients suffering from rheumatoid arthritis were enrolled. After an initial upper gastrointestinal endoscopy to rule out the presence of gastric mucosal lesions, the patients were randomly allocated in a double-blind, double-dummy manner, to receive either pirprofen (400 mg t.i.d.) or naproxen (500 mg b.i.d.) for 4 weeks; endoscopic control followed this treatment period, or was anticipated in the event of painful dyspepsia.
Endoscopy at the beginning of the study and at 4 weeks, or anticipated in the event of painful dyspepsia.
Primary outcome measure of the study was the possibility that pirprofen was less toxic to the gastric mucosa than naproxen, and at least as effective.
Both drugs proved effective in relieving clinical symptoms, without a statistically significant difference. Gastric mucosa lesions were observed in 90% of pirprofen-treated patients and in 60% of those on naproxen (P = 0.03). The most severe lesions (grades 3 and 4) were found in 65% of subjects treated with pirprofen, as opposed to 15% of those treated with naproxen (P = 0.001). | This study shows that pirprofen is at least as active as naproxen in relieving rheumatic symptoms, but its administration results in a significantly severe degree of gastric damage. |
3,344 | 23,722 | Quadriceps muscle weakness and vitamin D deficiency are associated with knee osteoarthritis (KOA). This study aimed to investigate the relationship between quadriceps muscle strength (QMS) and vitamin D in KOA.
Patients with KOA aged 40 years and above were studied. QMS was assessed by the dynanometry method and serum 25-hydroxyvitamin D (25-OHD) by the ELISA method. Serum 25-OHD<20 ng/mL was considered as a deficiency. The intensity of knee pain was determined by the Western Ontario and McMaster Universities Osteoarthritis Index Pain Scale. The Pearson test was used for correlation analysis between QMS and serum 25-OHD as well as knee pain.
A total of 92 patients (female, 80%) with a mean age of 49.6±11.7 years were studied. QMS was correlated positively with serum 25-OHD (r=0.304, r=9.24%, P=0.005) and negatively with knee pain (r=-0.232, r=5.3%, P=0.034). After adjustment for age, sex, and body mass index, the positive correlation increased to a higher level (r=0.496, r=24.9%, P=0.01). For each 1 ng/mL increase in serum 25-OHD, the value of QMS increased by 14.2%±3.5% (P=0.014). There was no significant correlation between serum 25-OHD and knee pain (P=0.13). | These findings demonstrated a significant correlation between QMS with both serum vitamin D and knee pain, indicating a confounding role for quadriceps muscle in the association between serum vitamin D and osteoarthritis knee pain. On the basis of the findings of this study, vitamin D supplementation may affect pain by strengthening quadriceps muscle in KOA. |
3,345 | 12,891 | To assess, using model-based dynamic radiostereometric analysis (RSA), the biomechanical behaviour of a new design posterior-stabilized (PS) fixed-bearing (FB) total knee arthroplasty (TKA) in vivo while patients performing two common motor tasks. The hypothesis was that model-based dynamic RSA is able to detect different behaviour of the implant under weight-bearing and non-weight-bearing conditions.
A cohort of 15 non-consecutive patients was evaluated by dynamic RSA 9 months after TKA implantation. The mean age of patients was 73.4 (65-72) years. The kinematic evaluations were performed using an RSA device (BI-STAND DRX 2) developed in our Institute. The patients were asked to perform two active motor tasks: sit-to-stand in weight-bearing condition; range of motion (ROM) while sitting on the chair. The motion parameters were evaluated using the Grood and Suntay decomposition and the low-point kinematics methods.
The dynamic RSA evaluation showed a significant difference (p < 0.05) between the biomechanical behaviour of the prosthesis during the two motor tasks. When subjected to the patient weight (in the sit-to-stand) the low point of the medial compartment had a shorter motion (5.7 ± 0.2 mm) than the lateral (11.0 ± 0.2 mm). This realizes a medial pivot motion as in the normal knee. In the ROM task, where the patient had no weight on the prosthesis, this difference was not present: the medial compartment had a displacement of 12.7 ± 0.2 mm, while the lateral had 17.3 ± 0.2 mm.
IV. | Model-based RSA proved to be an effective tool for the evaluation of TKA biomechanics. In particular, it was able to determine that the fixed-bearing posterior-stabilized TKA design evaluated in this study showed a medial pivoting movement under weight-bearing conditions that was not present when load was not applied. Under loading conditions what drives the pattern of movement is the prosthetic design itself. By the systematic use of this study protocol future comparisons among different implants could be performed, thus contributing significantly to the improvement of TKA design. |
3,346 | 48,711 | To evaluate various validity aspects of four disease activity scores (ASDAS) for ankylosing spondylitis (AS) in comparison with the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), its individual components and physician and patient global assessment of disease activity.
The analyses were performed in two cohorts of patients with AS: (1) the NOR-DMARD database which includes patients starting on a disease-modifying antirheumatic drug or tumour necrosis factor (TNF) blocker and (2) patients participating in double-blind placebo controlled randomised clinical trials with TNF blockers in four centres. Discrimination between patients with low versus high disease activity according to various definitions and between various levels of change were analysed as the standardised mean difference (difference in the group means divided by the pooled SD of the group means) and t score.
The four ASDAS versions were highly discriminatory in differentiating patients with different levels of disease activity and patients with different levels of change. The ASDAS scores outperformed the BASDAI and its single components in all settings: patient- or physician-based, reflecting status or change, with normal or raised C-reactive protein (CRP), in the presence or absence of peripheral arthritis. There were no major differences between the four ASDAS scores. Based on feasibility, the ASAS membership selected the ASDAS version which included back pain, duration of morning stiffness, patient global assessment, peripheral joint complaints and CRP as the preferred version. | The ASDAS is a validated, highly discriminatory instrument for assessing disease activity in AS, including patient-reported outcomes and CRP levels. |
3,347 | 46,750 | Systemic sclerosis (SSc) (scleroderma) is a complex autoimmune disease that clinically manifests as progressive fibrosis of the skin and internal organs. Anti-centromere antibodies (ACAs), anti-topoisomerase antibodies (ATAs), and anti-RNA polymerase III antibodies (ARAs) are three mutually exclusive SSc-associated autoantibodies that correlate with distinct clinical subsets characterized by extent of cutaneous involvement and pattern of organ involvement. The current report sought to determine whether plasma cytokine profiles differ in SSc patients grouped according to these SSc-associated autoantibody subsets.
Plasma from 444 SSc patients and 216 healthy controls was obtained from the Scleroderma Family Registry and University of Texas Rheumatology Division. Patients were classified according to the presence of ACAs, ATAs, ARAs, or none of the above (antibody-negative). Levels of 13 cytokines were determined using multiplex assays.
Compared with females, healthy control males had higher plasma levels of IL-2 (P = 0.008), IL-5 (P = 0.01) and IL-8 (P = 0.01). In addition, in controls, IL-6 (P = 0.02) and IL-17 (P = 0.01) levels increased with advancing age. After adjusting for age and gender, SSc patients had higher circulating levels of TNFalpha (P < 0.0001), IL-6 (P < 0.0001), and IFNgamma (P = 0.05) and lower IL-17 (P = 0.0005) and IL-23 (P = 0.014). Additional analyses demonstrated that disease duration also influenced these cytokine profiles. IL-6 was elevated in ATA-positive and ARA-positive patients, but not in ACA-positive patients. IL-8 was uniquely increased in the ATA-positive subset while both ATA-positive and ACA-positive subsets had elevated IFNgamma and IL-10. IL-5 was only significantly increased in the ACA-positive subset. Lastly, patients with interstitial lung disease had elevated IL-6 and patients with pulmonary hypertension had elevated IL-6 and IL-13. | Plasma cytokine profiles differ in SSc patients based on the presence of SSc-associated autoantibodies. Plasma cytokine profiles in SSc patients may also be affected by disease duration and the pattern of internal organ involvement. |
3,348 | 3,169 | Australian- and New Zealand-based, uveitis-specialized ophthalmologists have produced recommendations for the management of juvenile idiopathic arthritis (JIA)-type chronic anterior uveitis.
Historically, the visual prognosis of JIA-type chronic anterior uveitis has been poor. New medical advances are likely to improve outcomes, but recently published guidelines are tailored for ophthalmic care in Europe and the United States.
This work involved a consensus survey and a panel meeting.
The Australian and New Zealand JIA-Uveitis Working Group (29 ophthalmologists) participated in the work.
The Delphi technique was used to achieve consensus.
This work yielded consensus statements.
The Working Group achieved consensus around 18 statements related to clinical evaluation, use of topical and regional corticosteroids, use of systemic corticosteroid and non-corticosteroid immunomodulatory drugs, and management of secondary cataract and glaucoma in childhood JIA-type uveitis. | Recommendations of the Australian and New Zealand JIA-Uveitis Working Group provide current and regionally applicable advice for managing chronic anterior uveitis in children with JIA. |
3,349 | 51,448 | Evaluate long-term safety and efficacy of etanercept treatment in patients with ankylosing spondylitis (AS).
Patients with AS who previously participated in a randomised controlled trial (RCT) of etanercept were eligible to enroll in a 168-week open-label extension (OLE). Safety end points included rates of adverse events (AE), serious adverse events (SAE), infections, serious infections and death. Efficacy end points included Assessment in Ankylosing Spondylitis (ASAS20) response, ASAS 5/6 response and partial remission rates.
A total of 257 of 277 patients (92%) enrolled in the OLE. After up to 192 weeks of treatment with etanercept, the most common AEs were injection site reactions, headaches and diarrhoea. The exposure-adjusted rate of SAEs was 0.08 per patient-year. The rate of infections was 1.1 per patient-year, and the rate for serious infections was 0.02 per patient-year. No deaths were reported. Of patients who received etanercept in both the RCT and OLE and were still in the trial, 71% were ASAS20 responders at week 96, and 81% were responders at week 192. ASAS 5/6 response rates were 61% at week 96 and 60% at week 144, and partial remission response rates were 41% at week 96 and 44% at week 192. Placebo patients who switched to etanercept in the OLE showed similar patterns of efficacy maintenance. | Etanercept was well tolerated for up to 192 weeks in patients with AS, with no unexpected AEs or SAEs observed. No deaths were reported. Improvements in the signs and symptoms of AS were maintained for up to 192 weeks. |
3,350 | 66,467 | This study was performed to determine the compliance with the basic treatments for rheumatoid arthritis (RA; medication, physical therapy, and ergonomic measures), to study psychological factors that influence compliance in light of the social learning theory, to learn whether patient education positively influences compliance and health, and to find an approach to patient education that improves compliance.
A MEDLINE search of the English language literature was performed.
Few studies have dealt with compliance in RA patients; levels of adherence are generally low. According to the social learning theory, human function involves a continuous interaction between behavior, personal factors, and external environment. Self-efficacy is a personal factor that refers to the belief in one's capabilities and opportunities for being compliant with treatment advice. Patient education may improve ergonomic performance and compliance with physical exercise programs. | Compliance with medication was infrequently studied. Whether improved compliance leads to better health status could not be determined. Compliance with RA treatments are generally low. Systematic study of the effect of patient education on treatment and health is warranted. Self-efficacy enhancing techniques in patient education may improve compliance. |
3,351 | 4,924 | To explore the role of medial collateral ligament repair in knee osteoarthritis based on TLR4/ MyD88/ NF-κ inflammatory signaling pathway.
The modified Hulth method was used to establish models, which were divided into a repair group, a model group, and a sham operation group. The repair group was treated with medial ligament repair technology. Synovium and cartilage morphological changes were evaluated by hematoxylin-eosin staining to determine the degree of reparation. The cartilage was evaluated by the Mankin's score, and inflammatory factors in cartilage tissues were determined by ELISA. The changes in TLR4, MyD88, and NF-κB levels were analyzed using the real-time quantitative PCR and Western blot assays.
The synovial and cartilage damages in the repair group and the sham operation group were significantly alleviated compared to the model group. The Mankin's score of the model group was significantly lower than the other two groups. The expression of inflammatory factors in the repair group and the sham operation group were significantly lower than in the model group. The expressions of those factors in the repair group and the model group were higher than those in the model group. | Medial ligament repair can improve the cartilage morphology and delay the development and progression of knee osteoarthritis by inhibiting the TLR4/MyD88/NF-κB signaling pathway. |
3,352 | 5,317 | With 432 513 samples from UK Biobank dataset, multivariable linear/logistic regression were used to estimate the relationship between psoriasis/psoriatic arthritis (PsA) and estimated bone mineral density (eBMD)/osteoporosis, controlling for potential confounders. Here, confounders were set in three ways: model0 (including age, height, weight, smoking and drinking), model1 (model0 +regular physical activity) and model2 (model1 +medication treatments). The eBMD was derived from heel ultrasound measurement. And 4904 patients with psoriasis and 847 patients with PsA were included in final analysis. Mendelian randomisation (MR) approach was used to evaluate the causal effect between them.
Lower eBMD were observed in patients with PsA than in controls in both model0 (β-coefficient=-0.014, p=0.0006) and model1 (β-coefficient=-0.013, p=0.002); however, the association disappeared when conditioning on treatment with methotrexate or ciclosporin (model2) (β-coefficient=-0.005, p=0.28), mediation analysis showed that 63% of the intermediary effect on eBMD was mediated by medication treatment (p<2E-16). Patients with psoriasis without arthritis showed no difference of eBMD compared with controls. Similarly, the significance of higher risk of osteopenia in patients with PsA (OR=1.27, p=0.002 in model0) could be eliminated by conditioning on medication treatment (p=0.244 in model2). Psoriasis without arthritis was not related to osteopenia and osteoporosis. The weighted Genetic Risk Score analysis found that genetically determined psoriasis/PsA were not associated with eBMD (p=0.24 and p=0.88). Finally, MR analysis showed that psoriasis/PsA had no causal effect on eBMD, osteoporosis and fracture. | The effect of PsA on osteoporosis was secondary (eg, medication) but not causal. Under this hypothesis, psoriasis without arthritis was not a risk factor for osteoporosis. |
3,353 | 11,375 | Objective evaluation of disease activity is challenging in patients with juvenile dermatomyositis (DM) due to a lack of reliable biomarkers, but it is crucial to avoid both under- and overtreatment of patients. Recently, we identified 2 proteins, galectin-9 and CXCL10, whose levels are highly correlated with the extent of juvenile DM disease activity. This study was undertaken to validate galectin-9 and CXCL10 as biomarkers for disease activity in juvenile DM, and to assess their disease specificity and potency in predicting the occurrence of flares.
Levels of galectin-9 and CXCL10 were measured by multiplex immunoassay in serum samples from 125 unique patients with juvenile DM in 3 international cross-sectional cohorts and a local longitudinal cohort. The disease specificity of both proteins was examined in 50 adult patients with DM or nonspecific myositis (NSM) and 61 patients with other systemic autoimmune diseases.
Both cross-sectionally and longitudinally, galectin-9 and CXCL10 outperformed the currently used laboratory marker, creatine kinase (CK), in distinguishing between juvenile DM patients with active disease and those in remission (area under the receiver operating characteristic curve [AUC] 0.86-0.90 for galectin-9 and CXCL10; AUC 0.66-0.68 for CK). The sensitivity and specificity for active disease in juvenile DM was 0.84 and 0.92, respectively, for galectin-9 and 0.87 and 1.00, respectively, for CXCL10. In 10 patients with juvenile DM who experienced a flare and were prospectively followed up, continuously elevated or rising biomarker levels suggested an imminent flare up to several months before the onset of symptoms, even in the absence of elevated CK levels. Galectin-9 and CXCL10 distinguished between active disease and remission in adult patients with DM or NSM (P = 0.0126 for galectin-9 and P < 0.0001 for CXCL10) and were suited for measurement in minimally invasive dried blood spots (healthy controls versus juvenile DM, P = 0.0040 for galectin-9 and P < 0.0001 for CXCL10). | In this study, galectin-9 and CXCL10 were validated as sensitive and reliable biomarkers for disease activity in juvenile DM. Implementation of these biomarkers into clinical practice as tools to monitor disease activity and guide treatment might facilitate personalized treatment strategies. |
3,354 | 57,597 | To compare subjects who had at least one parent with a total knee replacement for severe primary knee osteoarthritis with age and sex matched controls who had no family history of knee osteoarthritis
Population based case-control study of 188 matched pairs (mean age 45 years, range 26 to 60).
Articular cartilage volume and bone size were determined at the patella and at the medial tibial and lateral tibial compartments by processing images acquired using T1 weighted, fat saturated magnetic resonance imaging. Radiographic osteoarthritis (ROA) was assessed from a standing semiflexed radiograph scored for joint space narrowing and osteophytosis. Knee pain was assessed by questionnaire. Height, weight, body mass index (BMI), lower limb muscle strength, and endurance fitness were measured by standard protocols.
Compared with the controls, index offspring had higher BMI (27.8 v 26.0 kg/m(2), p = 0.02), weaker lower limb muscles (127 v 135 kg, p = 0.006), more knee pain (47% v 22%, p<0.001), and greater medial tibial bone area (17.6 v 17.1 cm(2), p = 0.01). With the exception of BMI, these differences persisted in multivariate analysis. There was a non-significant trend to higher cartilage volume at tibial sites and increased ROA in the offspring in the total and subgroup analyses, but no difference in height and endurance fitness. | BMI, muscle strength, knee pain, and medial tibial bone area, but not cartilage volume, appear to play a role in the genetic regulation and development of knee osteoarthritis. |
3,355 | 16,722 | Rheumatoid arthritis (RA) is a predominant inflammatory autoimmune disorder. The incidence and prevalence of RA is increasing with considerable morbidity and mortality worldwide. The pathophysiology of RA has become clearer due to many significant research outputs during the last two decades. Many inflammatory cytokines involved in RA pathophysiology and the presence of autoantibodies are being used as potential biomarkers via the use of effective diagnostic techniques for the early diagnosis of RA. Currently, several disease-modifying anti-rheumatic drugs are being prescribed targeting RA pathophysiology, which have shown significant contributions in improving the disease outcomes.
Even though innovations in treatment strategies and monitoring are helping the patients to achieve early and sustained clinical and radiographic remission, the high cost of drugs and limited health care budgets are restricting the easy access of RA treatment. Both direct and indirect high cost of treatment are creating economic burden for the patients and affecting their quality of life. | The aim of this review is to describe the updated concept of RA pathophysiology and highlight current diagnostic tools used for the early detection as well as prognosis - targeting several biomarkers of RA. Additionally, we explored the updated treatment options with side effects besides discussing the global economic burden. |
3,356 | 61,429 | Matrix metalloproteinases (MMP) are a large family of proteolytic enzymes involved in the remodeling of extracellular matrix during tissue resorption in idiopathic arthritides. We investigated serum and synovial fluid (SF) concentrations of MMP-3 and its tissue inhibitor (TIMP-1) in juvenile idiopathic arthritides (JIA).
Sera from 45 patients with active, 15 patients with inactive JIA, and 15 healthy controls were evaluated by ELISA for MMP-3 (stromelysin-1), TIMP-1, and soluble p75 tumor necrosis factor receptor (sTNFR). Paired SF concentrations were evaluated in 19 patients with JIA.
MMP-3 serum concentrations were significantly higher in patients with active poly- and oligoarticular JIA versus inactive patients (p = 0.04 and p = 0.02, respectively) and healthy controls (p < 0.001 for both). Serum MMP-3, but not TIMP-1, concentration displayed a variable degree of correlation with clinical and laboratory variables of disease activity and with p75 sTNFR concentrations (r = 0.37, p = 0.005). SF MMP-3 concentrations were 30-300 times higher than those found in paired sera (p < 0.001, Wilcoxon rank test). A clear inversion of MMP-3/TIMP-1 ratio was observed when sera (median 0.31. range 0.02-1.5) were compared with the corresponding SF samples (5.3, range 4.9-5.5; p < 0.001). | MMP-3 (stromelysin-1) is clearly overexpressed in SF of patients with JIA. An inadequate counter-expression of TIMP-1 may represent a crucial event for the development and perpetuation of tissue damage. |
3,357 | 60,839 | To calculate mortality rate associated with rheumatoid arthritis (RA), to estimate the effect of initial functional status and of change in functional status on mortality among persons with RA, and to compare the mortality experience of such persons to that of the US population.
The study used a prospective panel of 1269 persons followed for a mean of 8.4 years (median 7 yrs, interquartile range 3-12, maximum 18). Mortality status was ascertained from contacts with next of kin, study physicians, and search of the National Death Index. The Kaplan-Meier method was used to calculate the proportion dying in each time interval, with and without stratification for initial functional status [Health Assessment Questionnaire (HAQ) score] or average change in functional status. Cox proportional hazards regression was used to establish the effect of functional status, demographic characteristics, and health status on mortality risk.
There were 270 deaths among the 1269 persons with RA. After 18 years of followup the overall death rate was 39%. The death rates in the best through worst initial quartiles of HAQ score were 29, 33, 44, and 54%. The death rate was 51% among persons with declining HAQ score versus 31 and 32% among those with no change or improvement in this measure, respectively. Demographic and health status did not reduce the effect of HAQ or average change in HAQ on mortality risk. Compared to the US population, the persons with RA had a standardized mortality rate of 1.32. | The persons with RA in this study had elevated mortality rates. Poor initial functional status and declining functional status significantly increased mortality risk among these persons with RA. |
3,358 | 7,519 | A 77-year-old woman with knee osteoarthritis (OA) complained of right (ipsilateral) knee pain for more than 5 years with gait asymmetry. The OA and quadriceps muscle weakness were more severe in the left (contralateral) knee, but she had no pain. Bracing of the left knee led to decreased gait asymmetry, as determined with an inertial measurement unit, and reduced pain in the right knee. | This case highlights the contralateral knee effect on ipsilateral chronic knee pain, possibly through gait asymmetry. These findings provide a mechanistic insight into knee OA-related pain in patients with gait asymmetry and suggest a new rehabilitative approach. |
3,359 | 61,978 | To provide data on (a) the probability of detecting antinuclear antibodies (ANA) in a large and consecutive cohort of serum samples referred for ANA testing and (b) the probability of detecting more specific antinuclear reactivities (anti-DNA and anti-extractable nuclear antigens (anti-ENA)) in serum samples with a positive screening test (indirect immunofluorescence on HEp-2 cells).
Serum samples from 10 550 consecutive patients sent to the laboratory for ANA detection were analysed. In ANA positive serum samples (23.5% of referred serum samples), ANA were identified by indirect immunofluorescence on Crithidia, by immunodiffusion, and by line immunoassay. Because anti-SSA antibodies were the most frequently identified ANA, sensitively detected by line immunoassay, additional immunoassays were developed to confirm the specificity of the line immunoassay result.
At least one fine reactivity could be identified in 21.1% of ANA positive serum samples: anti-dsDNA in 3.2%; anti-ENA (anti-SSA 10.5%, anti-SSB 6.7%, anti-RNP 2.7%, anti-Sm 1.8%, anti-Scl70 1.2%, anti-Jo-1 0.2%) in 15.8%, rRNP and anti-Cenp-B in respectively 0.5% and 4.0%. Multiple reactivities were found in 7.9%. For anti-ENA antibodies, line immunoassay was more sensitive than immunodiffusion (15.4% v 7.7%; p<0.0001). The sensitive detection of anti-SSA antibodies by line immunoassay was confirmed by additional assays. | The data from this analysis are useful in estimating the probabilities of detecting specific ANA. Line immunoassay was shown to be a sensitive test for the detection of anti-ENA antibodies. |
3,360 | 12,155 | Polymyalgia rheumatica (PMR) is a common inflammatory disorder that is usually managed with oral glucocorticoids, which although effective can cause significant adverse events. Support group survey data suggests length of glucocorticoid treatment and managing side effects are key priority areas of management for patients. Recognising that not all patients will access patient support organisations, our objective was to identify priorities for PMR management and research among primary care PMR patients.
All adults aged ≥ 50 years registered with 150 English general practices who had a first read code for PMR in their medical records in the preceding 3 years were mailed a self-completion questionnaire (n = 704). Survey items included questions regarding patient priorities for PMR management (from a pre-defined list of 10 items) and suggestions for future research (8 items, plus a free-text option), which were developed in collaboration with PMRGCAuk.
Five hundred fifty patients responded (78%). The mean (SD) age was 74.1 (8.5) years and 361 (66%) were female. Priority research areas were focused on how to better manage pain, stiffness and fatigue (431, 78%), improving the diagnosis of PMR (393, 71%) and steroid management (342, 62%). | This survey of PMR patients suggests that symptom management, early diagnosis and managing medication are key areas for patients for future research. Researchers and funding organisations should be aware of these priorities if we are to generate research findings that are relevant to the widest range of stakeholders. |
3,361 | 53,319 | To evaluate the feasibility of conducting an online case-crossover study of triggers for recurrent disease flares.
We conducted an online case-crossover study of triggers for recurrent flares using gout as a paradigm. We constructed a Web site and recruited individuals with history of gout via the Internet. We confirmed gout diagnosis by reviewing each subject's medical records. We collected via the Internet exposure information during the intercritical period using a scheduled Control-period Questionnaire, and prior to recurrent gout attacks using a Hazard-period Questionnaire.
Over 10 months we recruited 197 subjects with a history of gout from 41 states and the District of Columbia. We obtained medical records from 172 subjects. All participants had experienced at least one recurrent attack and filled out required questionnaires. The median time between the date of an attack and the date of logging on to the Web site was 2 days. The incidence rate of recurrent gout attacks was 1.03 per person-year. Longer disease duration and presence of comorbidities appeared to increase the risk of recurrent flares. | The results of this study demonstrate that a case-crossover study can be successfully conducted through the Internet. This approach has broad applicability to other diseases typified by recurrent attacks. |
3,362 | 38,894 | To investigate the disease modifying effects of cathepsin K (CatK) inhibitor L-006235 compared to alendronate (ALN) in two preclinical models of osteoarthritis (OA).
Skeletally mature rabbits underwent sham or anterior cruciate ligament transection (ACLT)-surgery and were treated with L-006235 (L-235, 10 mg/kg or 50 mg/kg, p.o., daily) or ALN (0.6 mg/kg, s.c., weekly) for 8-weeks. ACLT joint instability was also induced in CatK(-/-) versus wild type (wt) mice and treated for 16-weeks. Changes in cartilage degeneration, subchondral bone volume and osteophyte area were determined by histology and μ-CT. Collagen type I helical peptide (HP-I), a bone resorption marker and collagen type II C-telopeptide (CTX-II), a cartilage degradation marker were measured.
L-235 (50 mg/kg) and ALN treatment resulted in significant chondroprotective effects, reducing CTX-II by 60% and the histological Mankin score for cartilage damage by 46% in the ACLT-rabbits. Both doses of L-235 were more potent than ALN in protecting against focal subchondral bone loss, and reducing HP-I by 70% compared to vehicle. L-235 (50 mg/kg) and ALN significantly reduced osteophyte formation in histomorphometric analysis by 55%. The Mankin score in ACLT-CatK(-/-) mice was ~2.5-fold lower than the ACLT-wt mice and was not different from sham-CatK(-/-). Osteophyte development was not different among the groups. | Inhibition of CatK provides significant benefits in ACLT-model of OA, including: 1) protection of subchondral bone integrity, 2) protection against cartilage degradation and 3) reduced osteophytosis. Preclinical evidence supports the role of CatK as a potential therapeutic target for the treatment of OA. |
3,363 | 50,382 | To gain insight into the personal experience and feelings of an adolescent with a chronic disease.
We report on the application of the self-confrontation method (SCM), illustrated by a case-example of an adolescent with juvenile idiopathic arthritis.
Although taken at face value she was not impeded by the arthritis, through self-assessment with the SCM this adolescent acknowledged and addressed the emotional struggle to keep the arthritis secret and to constantly test the physical limits of her body. After the process of self-reflection, the adolescent showed a better integration of her arthritis experiences into her life story.
In future research, by studying the self-investigations of a group of adolescents with chronic diseases, common risk factors for the development of a stable identity during adolescence might be identified. In clinical care, the SCM promotes self-knowledge, allowing for an intrinsic motivation to deal with the emotional impact of the disease. | With the SCM the adolescent could explore her own functioning and well-being on a manifest, as well as on an emotional and motivational level. |
3,364 | 23,483 | While rheumatoid arthritis is an established risk factor for cardiovascular disease (CVD), our knowledge of how the pattern of risk varies for different cardiovascular phenotypes is incomplete. The association between rheumatoid arthritis and the initial presentation of 12 types of CVDs were examined in a contemporary population of men and women of a wide age range.
CALIBER data, which links primary care, hospital and mortality data in England, was analysed. A cohort of people aged ≥18 years and without history of CVD was assembled and included all patients with prospectively recorded rheumatoid arthritis from January 1997, until March 2010, matched with up to ten people without rheumatoid arthritis by age, sex and general practice. The associations between rheumatoid arthritis and the initial presentation of 12 types of CVDs were estimated using multivariable random effects Poisson regression models.
The analysis included 12,120 individuals with rheumatoid arthritis and 121,191 comparators. Of these, 2,525 patients with and 18,146 without rheumatoid arthritis developed CVDs during a median of 4.2 years of follow-up. Patients with rheumatoid arthritis had higher rates of myocardial infarction (adjusted incidence ratio [IRR] = 1.43, 95%CI 1.21-1.70), unheralded coronary death (IRR = 1.60, 95%CI 1.18-2.18), heart failure (IRR = 1.61, 95%CI 1.43-1.83), cardiac arrest (HR = 2.26, 95%CI 1.69-3.02) and peripheral arterial disease (HR = 1.36, 95%CI 1.14-1.62); and lower rates of stable angina (HR = 0.83, 95%CI 0.73-0.95). There was no evidence of association with cerebrovascular diseases, abdominal aortic aneurysm or unstable angina, or of interactions with sex or age. | The observed associations with some but not all types of CVDs inform both clinical practice and the selection of cardiovascular endpoints for trials and for the development of prognostic models for patients with rheumatoid arthritis. |
3,365 | 45,518 | Previous research has largely focused on the lived experience either of those who have fibromyalgia syndrome (FMS) or their spousal carers. This study aimed to explore the lived experiences of both those with FMS and their spousal carers.
Participants were aged between 38 and 65 years and all came from the south-west of England. Semi-structured interviews were conducted with four women with FMS and their spousal carers, who were interviewed separately. The resultant transcripts were analysed using interpretative phenomenological analysis. An overriding theme running throughout was loss of identity, which fed into a sense of isolation. Participants reported feeling isolated from: healthcare professionals, whom they felt they had to convince that they had something 'real', and from friends and family because the unpredictability of their symptoms meant that they were less able to plan ahead and often had to pull out of arranged outings. They also felt isolated from their identity because they no longer recognized the person that they once were, and struggled to recognize the person that they had become. As a consequence, the people with FMS and their carers were both engaged in a process of reassessing who they were, now that FMS had become such a large part of their lives. This sense of isolation was evidenced for the carers as well as the people with FMS and is documented in three sub-themes described in the paper: 'others' attitudes', 'invisible illness' and 'role'. | This study has provided new information regarding the lifeworlds both of people living with FMS and their spousal carers. We identified a number of practical and attitudinal barriers that had led to the diminution of social networks for both members of the couple and have explored the related clinical and theoretical implications of this. |
3,366 | 13,601 | Informed consent (IC) is an ethical process required in human subject research. Primary objective was to determine factors associated to poor knowledge of IC content (PK) in patients from an early rheumatoid arthritis cohort.
The cohort initiated in 2004, had assistant and research purposes (NCT03389711). At inclusion, each patient selected 1 of 4 options of the IC form; options ranged from broad consent (patient's data could be used for research) to patient denied to have his/her data used. Once enrolled, patients had regular assessments. Up to May 2017, the cohort had 146 patients with (median, range) follow-up of 8.8 years, (4.3-11.9) and 143 agreed to participate in a cross-sectional study; patients had scheduled rheumatic evaluations; additionally, a social worker applied a questionnaire that addressed objective described. PK was established by the borderline performance method. Multiple regression models were applied to investigate factors associated to PK.
At cohort inclusion, patients were primarily middle-aged (38.3±13.1 years) females (88.9%), with high disease activity (DAS28: 5.8 [4.6-6.8)] and poor quality of life (SF-36: 42 [29-59]). All the patients gave broad IC. At study entry, 35-41.3% of them had PK; longer follow-up and lower SF-36 scores at cohort inclusion, were associated to PK. In addition, 79.7% of the patients had DAS28-remission and 67.1% had SF-36 scores within normal range; interestingly, only 49% of the patients considered broad re-consent and these patients had poorer SF-36 emotional subscore than their counterpart (79±23 vs. 87±1, p=0.02). | Poor quality of life impacts the autonomy of RA patients. |
3,367 | 64,364 | To define the onset and duration of effect of the HLA alleles that are associated with disease susceptibility and protection in juvenile rheumatoid arthritis (JRA) and 2 of its subtypes.
We typed 680 patients with JRA and 254 ethnically matched unrelated controls for HLA class I and II genes. The frequency of each allele was calculated for each of the age-at-onset, onset type, and sex categories and plotted against the allele frequency in the control population. Survival analysis (with onset of disease as the terminating event) was used to calculate the age by which 50% (St0.5) and 80% (St0.2) of the children with particular alleles and combinations of alleles develop disease. This allele-specific survival analysis also allowed for the comparison of the overall survival functions for the various JRA subtype and sex categories.
Certain alleles are strongly associated with early susceptibility to pauciarticular JRA, including HLA-A2, DR8, DR5, and DPB1*0201. Fifty percent of the children carrying at least 1 of these alleles had disease onset prior to their third birthday. Among children who carried HLA-A2 and any 2 HLA-DR alleles (DR3, DR5, DR6, or DR8), the median age at the onset of pauciarticular disease was 2.7 years. Combinations of A2 and DPB1*0201 and one DR allele narrowed the window further to a median age at onset of 2.4 years. B27 and DR4 were associated with protection early in life but with increased risk later in childhood, with St0.5 values of 7.3 and 6.6 years, respectively, for pauciarticular JRA and St0.5 values of 10.2 and 10.7 years, respectively, for polyarticular JRA. Sex strongly influenced the age at which many of the alleles have their effect. | These data define at what age and for how long various HLA alleles influence susceptibility and protection (window-of-effect) in patients with JRA. In addition, these data establish more clearly the boundaries of ages-at-onset for 2 of the subtypes of the disease. |
3,368 | 44,440 | To compare healthcare utilization and costs in the year preceding and following initial diagnosis of fibromyalgia (FM).
Using a large US health insurance claims database, we identified all persons with newly diagnosed FM (International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis code 729.1) between January 1, 2003, and December 31, 2005 ("FM patients"). Each patient's first-noted claim with a diagnosis of FM was designated the "index date," and all pharmacy, outpatient, and inpatient claims were compiled over the 12-month periods preceding and following this date ("prediagnosis" and "postdiagnosis," respectively). Patients with incomplete pre- or postdiagnosis data were excluded. Healthcare utilization and costs were compared between the 2 periods.
A total of 1803 patients met all study inclusion criteria; mean (SD) age was 50.4 (9.4) years; 91% were women. Comorbidities were common, including arthritis (21% of study subjects), back pain (20%), and painful neuropathic disorders (16%). The percentage of study subjects receiving various pain-related medications increased from pre- to postdiagnosis, including opioids (51.3% vs 55.9%), antiepileptics (22.6% vs 28.6%), and tricyclic antidepressants (15.5% vs 21.2%) (all P <.01). Mean total healthcare costs also increased by $1725 between these periods (mean [95% confidence interval]: $9324 [$8655, $10,092] vs $11,049 [$10,245, $11,973], respectively; P <.01). | Patients with FM are often seen for other medical problems prior to initial diagnosis. Levels of healthcare utilization and costs are high during both the pre- and postdiagnosis periods. |
3,369 | 59,562 | Object of this work is to evaluate activity and tolerance of Celecoxib in out-patient's department practice.
In this study we enlisted 46 patients, affected by pain of inflammatory or degenerative origin; any of them ever did continued therapy with NSAIDs before. We administered 200 mg daily dose of Celecoxib for at least three months. Each patient has been evaluated by the Visual Analogic Score (VAS) Scale before and after the therapy.
The data We obtained agree with those of multicenter studies like CLASS. Celecoxib had similar efficacy respect with traditional NSAIDs, with good control of pain in both osteoarthrosic and arthritic pain (p < 0.000). Not good results were obtained for control of acute-onset pain. In our population We didn't find side-effects different from those included in the technical-form of the drug. The only patient who complained of epigastric pain did not stop the treatment, because the symptom resolved with assumption of the drug during meals. | By the analysis of the results We consider Celecoxib useful for the control of pain in the treatment of osteoarthrosis and autoimmune diseases like Rheumatoid Arthritis. Anyway, treatment with Celecoxib (as with all Coxib-family drugs) should be reserved for long-lasting treatments in patients at risk for gastrointestinal bleeding. |
3,370 | 1,816 | We present a fully automated method for the quantification of knee alignment from full-leg radiographs.
A state-of-the-art object detector, YOLOv4, was trained to locate regions of interests in full-leg radiographs for the hip joint, knee, and ankle. Residual neural networks were trained to regress landmark coordinates for each region of interest. Based on the detected landmarks the knee alignment, i.e., the hip-knee-ankle (HKA) angle was computed. The accuracy of landmark detection was evaluated by a comparison to manually placed ones for 180 radiographs. The accuracy of HKA angle computations was assessed on the basis of 2,943 radiographs by a comparison to results of two independent image reading studies (Cooke; Duryea) both publicly accessible via the Osteoarthritis Initiative. The agreement was evaluated using Spearman's Rho, weighted kappa, and regarding the correspondence of the class assignment.
The average deviation of landmarks manually placed by experts and automatically detected ones by our proposed "YOLOv4 And Resnet Landmark regression Algorithm" (YARLA) was less than 2.0 ± 1.5 mm for all structures. The average mismatch between HKA angle determinations of Cooke and Duryea was 0.09 ± 0.63°; YARLA resulted in a mismatch of 0.09 ± 0.73° compared to Cooke and of 0.18 ± 0.67° compared to Duryea. Cooke and Duryea agreed almost perfectly with respect to a weighted kappa value of 0.86, and showed an excellent reliability as measured by a Spearman's Rho value of 0.98. Similar values were achieved by YARLA, i.e., a weighted kappa value of 0.83 and 0.87 and a Spearman's Rho value of 0.98 and 0.98 compared to Cooke and Duryea, respectively. Cooke and Duryea agreed in 91% of all class assignments and YARLA did so in 90% against Cooke and 92% against Duryea. | YARLA yields HKA angles similar to those of human experts and provides a basis for an automated assessment of knee alignment in full-leg radiographs. |
3,371 | 13,753 | To characterize the orofacial abnormalities in patients with rheumatoid arthritis (RA) and compare them with those in a reference population.
The study included 30 RA patients and 30 consecutive patients in an odontology clinic in whom RA was ruled out. Patients underwent a clinical dental examination which included: 1) clinical and radiographic abnormalities of the temporomandibular joint; 2) biomechanical craniocervical analysis; 3) state of dentition and treatment needs; 4) periodontal status; 5) oral hygiene status; and 6) facial pain, which was compared among study groups. In addition, the association between the variables studied was determined through correlation tests.
Patients with RA showed a higher prevalence of temporomandibular abnormalities, both clinical (100.0% vs. 60.0%, P<.001) and radiographic, including erosions (50.0% vs. 16.0%, P=.010), compared with individuals in the control group. Likewise, patients with RA had a greater number of missing teeth (6.9±5.7 vs. 3.0±2.0, P=.001), more caries (13.4±5.4 vs. 4.9±6.5, P=.001), periodontitis (1.3±0.9 vs. 0.8±0.8, P=.015), poorer oral hygiene (43.3% vs. 13.3%, P=.005) and greater facial pain (66.7% vs. 20.0%, P <.001). The cephalometric analysis of Rocabado showed differences in the craniocervical angle and hyoid triangle between RA and controls. Significant correlations were obtained between oral and temporomandibular abnormalities. | Patients with RA showed a greater orofacial deterioration, which reflects the importance of multidisciplinary care, including periodic dental examination. |
3,372 | 13,892 | The progressive, debilitating nature of knee and hip osteoarthritis can result in severe, persistent pain and disability, potentially leading to a need for total joint arthroplasty (TJA) in end-stage osteoarthritis. TJA in adults with obesity is associated with increased surgical risk and prolonged recovery, yet classifying obesity only using body mass index (BMI) precludes distinction of obesity phenotypes and their impact on surgical risk and recovery. The sarcopenic obesity phenotype, characterized by high adiposity and low skeletal muscle mass, is associated with higher infection rates, poorer function, and slower recovery after surgery in other clinical populations, but not thoroughly investigated in osteoarthritis. The rising prevalence and impact of this phenotype demands further attention in osteoarthritis treatment models of care, particularly as osteoarthritis-related pain, disability, and current treatment practices may inadvertently be influencing its development.
A scoping review was used to examine the extent of evidence of sarcopenic obesity in adults with hip or knee osteoarthritis. Medline, CINAHL, Web of Science and EMBASE were systematically searched from inception to December 2017 with keywords and subject headings related to obesity, sarcopenia and osteoarthritis.
Eleven studies met inclusion criteria, with indications that muscle weakness, low skeletal muscle mass or sarcopenia are present alongside obesity in this population, potentially impacting therapeutic outcomes, and TJA surgical risk and recovery. | Consideration of sarcopenic obesity should be included in osteoarthritis patient assessments. |
3,373 | 39,130 | The aim of the present study was to investigate if assymetric dimethylarginine (ADMA) is increased in patients with rheumatoid arthritis (RA) compared to healthy controls and to examine associations between ADMA, RA disease activity and in vivo assessments of microvascular and macrovascular endothelial function.
Sixty-seven RA patients (age [mean ± standard deviation]: 56 ± 12 years, disease duration median [25th-75th percentile]: 8 [3-15] years, 48 women) and 29 healthy controls (age [mean ± standard deviation]: 42 ± 12, 21 women) underwent assessments of microvascular endothelial function (Laser Doppler imaging with iontophoresis of acetylcholine and sodium-nitroprusside), and macrovascular endothelial function (flow-mediated dilatation and glyceryl-trinitrate-mediated dilatation) as well as arterial stiffness. ADMA levels were measured in contemporary specimens using an immunoassay ELISA kit.
ADMA levels were significantly higher (p=0.004) in RA patients compared with healthy controls after adjustment for age (difference=0.088, 95% confidence interval 0.029-0.147). ADMA levels did not correlate with demographic or disease characteristics. No correlation was found between ADMA and microvascular and macrovascular endothelial function or with arterial stiffness. | ADMA levels are increased in patients with RA but there was no significant correlation with in vivo assessments of endothelial function. Further studies are needed to unfold the pathophysiological role of nitric oxide/ADMA pathway derangement in endothelial dysfunction and cardiovascular risk in RA. |
3,374 | 21,567 | Sarilumab is a human monoclonal antibody directed against the alpha subunit of the interleukin-6 receptor complex. In the MOBILITY phase III randomized controlled trial (RCT), sarilumab + methotrexate (MTX) treatment resulted in clinical improvements at 24 weeks that were maintained at 52 weeks in adults with rheumatoid arthritis (RA), who have inadequate response to MTX (MTX-IR). These analyses indicate the effects of sarilumab + MTX versus placebo on patient-reported outcomes (PROs) in this RCT.
Patients (n = 1197) were randomized to receive placebo, sarilumab 150 or 200 mg subcutaneously + MTX every 2 weeks for 52 weeks; after 16 weeks, patients without ≥20 % improvement from baseline in swollen or tender joint counts on two consecutive assessments were offered open-label treatment. PROs included patient global assessment of disease activity (PtGA), pain, health assessment questionnaire disability index (HAQ-DI), Short Form-36 Health Survey (SF-36), and functional assessment of chronic illness therapy-fatigue (FACIT-F). Changes from baseline at weeks 24 and 52 were analyzed using a mixed model for repeated measures. Post hoc analyses included percentages of patients reporting improvements equal to or greater than minimal clinically important differences (MCID) and normative values in the FACIT-F and SF-36. Pearson correlation between observed PRO scores and clinical measures of disease activity was tested at week 24.
Both doses of sarilumab + MTX vs placebo + MTX resulted in improvement from baseline by week 24 in PtGA, pain, HAQ-DI, SF-36 and FACIT-F scores (p < 0.0001) that was clinically meaningful, and persisted until week 52. In post hoc analyses, the percentages of patients with improvement equal to or greater than the MCID across all PROs were greater with sarilumab than placebo (p < 0.05), with differences ranging from 11.6 to 26.2 %, as were those reporting equal to or greater than normative scores.
ClinicalTrials.gov. NCT01061736 . February 2, 2010. | In this RCT in patients with MTX-IR RA, sarilumab + MTX resulted in sustained improvement in PROs that were clinically meaningful, greater than placebo + MTX, and complement the previously reported clinical efficacy and safety of sarilumab. |
3,375 | 58,446 | Recent randomized controlled trials (RCTs) in rheumatoid arthritis (RA) have used patient- and physician-reported outcomes, ESR and/or CRP as components of ACR response criteria to assess efficacy.
Mean changes from baseline in patient- and physician-reported outcome measures, ESR and CRP were compared in two RCTs in patients with active RA. Comparisons between active and placebo treatment used mean percentage improvements and standard effect sizes (SESs).
In both protocols, patient-reported assessments of disease activity, pain and physical function reflected little or no improvement with placebo, best discriminating between active and placebo therapy, as did ESR and CRP. | Improvements in signs and symptoms of active RA in placebo RCTs appear to be best reflected by patient-reported measures of physical function, as long as reported changes in global assessments of disease activity and/or pain reflect similar benefit. Patient-reported outcome measures should be considered objective; treatment-associated changes are congruent with measures of inflammation, and appear less susceptible to the placebo response. |
3,376 | 62,652 | The risk for serious gastrointestinal complications due to nonsteroidal anti-inflammatory drugs (NSAIDs) is high in the elderly. Acetaminophen-based regimens are safer and may be as effective as NSAIDs for the treatment of osteoarthritis in many patients.
To determine the effects of an educational program on NSAID use and clinical outcomes in nursing homes.
Randomized controlled study. Ten pairs of Tennessee nursing homes with > or = 8% of residents receiving NSAIDs were randomized to intervention or control.
Nursing home residents (intervention n = 76 and control n = 71) aged 65 years and older taking NSAIDs regularly.
An educational program for physicians and nursing home staff that included the risks and benefits of NSAIDs in the elderly and an algorithm that substituted acetaminophen, topical agents, and nonpharmacologic measures for the treatment of noninflammatory musculoskeletal pain. Intervention and control subjects were assessed at baseline and 3 months later.
Differences in NSAID and acetaminophen use, and pain, function, and disability scores in intervention and control nursing home subjects.
The intervention was effective resulting in markedly decreased NSAID use and increased acetaminophen use. Mean number of days of NSAID use in the 7 day periods before the baseline and 3 month assessments decreased from 7.0 to 1.9 days in intervention home subjects compared with a decrease from 7.0 to 6.2 days in control homes (P = 0.0001). Acetaminophen use in the 7 days immediately before the 3 month assessment increased by 3.1 days in intervention home subjects compared with 0.31 days in control homes (P = 0.0001). A similar proportion of subjects in control (32.5%) and intervention (35.4%) groups had worsening of their arthritis pain score (P = 0.81). | An educational intervention effectively reduced NSAID use in nursing homes without worsening of arthritis pain. |
3,377 | 53,313 | This study sought to understand patients' experiences of activity limitation in rheumatoid arthritis (RA) to inform the development and preliminary validation of a new patient-centred assessment tool.
Interviews, focus groups and diaries provided insight into patients' experiences of change in activity limitation. These data informed item generation for the Measure of Activity Limitation (MAL) questionnaire. Postal surveys, comprising the MAL, Short Form 36 (SF36) and Health Assessment Questionnaire (HAQ), were used to inform item reduction and assess the MAL's validity, reliability and sensitivity.
Qualitative exploration of activity limitation with 30 patients led to the development of a 36-item questionnaire addressing the impact of symptoms on activity, difficulty in global function and difficulty in task performance. Analysis of data from a postal survey of 168 patients led to the development of a 19-item questionnaire which demonstrated moderate correlations with the HAQ and relevant scales of the SF36. A second postal questionnaire, completed on two occasions by 308 patients, assessed test-retest reliability. One hundred and ninety-three people reporting no change in disease showed mean change in MAL score between the two completions of 0.41 [95% confidence interval (CI) -0.38 -1.22)], demonstrating test-retest reliability. Thirty-two patients reporting improvement showed a mean change of -7.84 (95% CI -11.15 to -4.54) and 83 reporting deterioration showed mean change of 4.63 (95% CI 3.09-6.16), suggesting that the MAL is sensitive to self-reported clinical change. | Our results suggest that the MAL is valid, reliable and sensitive to self-reported change. The MAL may provide a useful patient-centred adjunct to existing measures of activity limitation. |
3,378 | 37,054 | We investigated the decision-making preferences of rheumatoid arthritis (RA) patients using two different scales: the Decision Making Preference Scale (DMPS) and the modified Control Preference Scale (CPS). In addition, we evaluated the factors associated with patients' preferences for decision-making.
A cross-sectional study was performed using a self-administered anonymous questionnaire between October and December 2010 on 406 RA outpatients who consecutively visited 3 hospitals in Japan. The following variables were investigated: (1) DMPS, which is a subscale of the Autonomy Preference Index, composed of six items; patients responded on a 5-point Likert scale. (2) The modified CPS, in which patients were asked to choose one actual and one desired role in decision-making from among three options (passive role, collaborative role, and active role). (3) Sociodemographic data and RA-specific characteristics. Multivariate analyses were used to assess the relationship between patients' preferences and selected variables.
The response rate was 58.6 %. There were few patients who wished to make their own decisions when they were hospitalized or illness became worse. However, the majority of patients desired to collaborate with the doctor in making treatment decisions according to the results of modified CPS. The results of modified CPS were significantly associated with the total scores of DMPS. Multivariate analysis demonstrated they younger age and not-housewife were associated with high scores of DMPS. | Patient preferences in decision-making vary at RA outpatient clinic. Physicians need to assess decision-making preferences on an individual basis. |
3,379 | 50,288 | Chondroitin sulphate (CS) is an important structural component of cartilage and is approved and regulated as a symptomatic slow-acting drug for osteoarthritis (OA) (SYSADOA) in Europe and some other countries. Although numerous studies have shown the clinical benefits of CS to decrease pain, improve functional disability, reduce non-steroidal anti-inflammatory drug (NSAID) or acetaminophen consumption, and good tolerability with an additional carry-over effect, there are still some concerns regarding its effectiveness in treating OA.
To examine the data provided by meta-analyses to clarify the effectiveness of CS as a symptomatic treatment for OA.
A MEDLINE database search was conducted for appropriate meta-analyses published between 1997 and 2007. Five meta-analyses that limited their analysis to randomised controlled trials (RCTs) comparing CS with placebo or no-treatment control arms were retrieved.
Four meta-analyses showed significant clinical effects of CS compared with placebo for pain and function measures and one demonstrated greater reduction of analgesic co-medication in patients assigned to the active treatment. In one meta-analysis, the 20 trials included in the study showed a high degree of heterogeneity and the conclusion that CS showed minimal symptomatic benefits was based on the analysis of only three trials. One meta-analysis showed that pain relief after CS treatment steadily increased between 4 and 12 weeks of treatment, whereas the time course of pain relief after treatment with NSAIDs decreased. Two meta-analyses reported consistently higher frequencies of side effects in the placebo group than in patients treated with CS. | Data provided by these meta-analyses indicate that CS has a slight to moderate efficacy in the symptomatic treatment of OA, with an excellent safety profile. |
3,380 | 59,117 | The subchondral plate and its reconstitution has been an under-researched aspect of articular cartilage repair. The extent to which the subchondral plate is restored by natural healing remains controversial. This study aimed to quantify advancement of subchondral bone during repair of an osteochondral defect, and to examine the effect of subchondral bone height on the quality of articular surface repair.
Osteochondral defects, 3mm diameter by 3mm deep, were made by controlled drilling through the articular surface into the subchondral bone in femoral condyles of 33 rabbits. The repair response was examined at 8, 16 and 32 weeks (n=14, 12 and 7, respectively) post surgery. The specimens were subjected to mechanical testing, radiography, histology and histomorphometrology using an image analysis system.
At 8 weeks, the level of reparative subchondral bone was 0.79+/-0.36 mm below the native tidemark. By 16 weeks, reformed subchondral plate was irregular, showing that 76.5% of the plate had extended beyond the native tidemark (0.13+/-0.05 mm) whilst 16.9% of the plate remained below (0.19+/-0.15 mm). The repaired surface non-osseous layer became thinner than the adjacent cartilage (0.23+/-0.08 vs 0.38+/-0.11 mm, P<0.05). This persisted up to 32 weeks. The repaired surface layers showed disappearance of safranin-O staining, increased separation splits at the boundary, and eventual degradation. General histological scores were similar across 8, 16 and 32 weeks although the scores of defect filling and restoration of osteochondral junction were decreased from 8 to 16 weeks. Mechanically, repaired defects had lower contact pressure and greater indentation than the normal controls at all time (P<0.05). Indentations of the cartilage adjacent to the defects were also greater than the normal at 8 and 32 weeks (P<0.05). | The reparative subchondral bone advanced beyond the level of the native subchondral plate by 16 weeks in osteochondral defects of the rabbit femoral condyles. The presence of an advanced and irregular subchondral plate was associated with degradation of repaired articular surface. Abnormal subchondral plate is likely one of the major factors in influencing the long-term outcome of articular cartilage repair. |
3,381 | 20,113 | To identify whether hip arthroscopy is a suitable option for treating hip pain in elderly patients and investigate the clinical outcomes of hip arthroscopic surgery for labrum tear and/or osteoarthritis in patients over 50 years of age.
Between August 2009 and May 2014, a series of 23 patients (6 men and 17 women) with a mean age of 59 years underwent arthroscopy. We retrospectively examined the clinical records, radiographs, and outcome questionnaires from all patients. The mean follow-up period was 28 months.
The mean Japan Orthopedic Association hip score after surgery improved by a statistically significant amount. Eight patients (34.8%) were noted to have a progression of osteoarthritis (OA) diagnosed by radiograph, and one underwent THA after 13 months following arthroscopic surgery. The patients in which OA progression was noted were identified as having radiographical OA preoperatively and acetabular cartilage damage in the arthroscopic findings. | Arthroscopic surgery performed in selected patients over 50 years of age might be beneficial if classified as Tönnis grade 0 preoperatively and/or classified as Outerbridge grade II in the arthroscopic findings. |
3,382 | 11,387 | Inflammation-related symptoms such as pain, swelling and tenderness of the affected joint are frequently assessed using 5-point diary rating scales in gout clinical trials. Combining these into a single gout attack symptom intensity score may be a useful summary measure for these data, which is potentially more responsive to change compared with the individual components. The objective of this study was to develop a patient-reported gout flare intensity score, the Gout Attack Intensity Score (GAIS), for use in clinical studies, that includes components for gout-related pain, swelling and tenderness.
Data from a randomized controlled trial comparing anakinra to standard of care for the treatment of acute gout attacks were used for this study. A 7-day flare diary was completed by patients, including questions relating to intensity of pain, swelling and tenderness (5-point rating scales). Scalability of these items was assessed using Mokken Scale Analysis, and reliability using greatest lower bound reliability coefficients. Known-groups validity was evaluated, as well as the responsiveness to change and the presence of floor and ceiling effects.
Scalability of the single items was supported, and GAIS scores were reliable (greatest lower bound >0.80). GAIS scores demonstrated responsiveness to change with high effect sizes (>0.8), and discriminated better between responders and non-responders compared with its single-item components. No floor and ceiling effects were found. | The GAIS seems to be a reliable and responsive instrument for assessing patient-reported gout attack intensity that may be used in gout clinical studies. |
3,383 | 62,353 | The Rheumatoid Arthritis Quality of Life questionnaire (RAQoL) was developed simultaneously in the UK and the Netherlands to measure quality of life in patients with RA. We adapted and validated the RAQoL for the English-Canadian and French-Canadian languages and culture.
The UK RAQoL was translated into French-Canadian by a bilingual translation panel. Separate lay panels were then used to ensure that this and the English-Canadian instruments were appropriate for use with Canadian patients. Interviews were conducted with 15 French-Canadian and 15 English-Canadian patients with RA to determine the content validity. Reliability and construct validity were established by means of test-retest mail surveys conducted with 92 French-Canadian and 87 English-Canadian RA patients. The survey consisted of the adapted RAQoL, the Health Assessment Questionnaire (HAQ), and a demographic questionnaire.
The RAQoL was successfully adapted for both the French and English-Canadian cultures. Field testing showed both versions to be well received by respondents. Of the French-Canadian patients included in the postal survey, 52 responded at Time 1 and 50 at Time 2. For the English-Canadian sample, 54 responded at both time points. Missing data rates for the RAQoL were low and floor and ceiling effects were minimal. Test-retest reliability was good for both versions: 0.87 for the French-Canadian and 0.95 for the English-Canadian. Alpha coefficients (0.92 for the French-Canadian, 0.93 for the English-Canadian) showed the items to be adequately interrelated and scores on the measure showed moderate to high correlations with the HAQ, confirming construct validity. Both versions of the RAQoL were also able to distinguish patient groups that differed according to perceived health status and perceived severity of RA. In addition, the French-Canadian version was able to distinguish patients who rated today as bad or very bad from those who rated today as good or very good. | The new versions of the RAQoL were well received by both French and English speaking Canadians. The psychometric quality of the adapted questionnaires means they are suitable for inclusion in clinical trials involving patients with RA. |
3,384 | 20,796 | Debate exists regarding the effect of triple fusion on the development of osteoarthritis (OA) of the ankle joint. The midterm outcome after triple arthrodesis and the prevalence of OA following triple arthrodesis are reported in this study. The role of alignment in the development of OA was investigated.
Seventy five patients (87 feet) were evaluated in 2003 and of these, 48 patients (55 feet) were available for second evaluation in 2008. X-rays of the ankles and feet were made prior to surgery, in 2003 and in 2008, and the level of osteoarthritis (OA) was graded with the Kellgren and Lawrence score. Of all postoperative X-rays, the AP and lateral talo first metatarsal angle X-rays were compared. Also, standardized digital photos were made to assess the geometry/alignment. The Foot Function Index (FFI) and the American Orthopaedic Foot and Ankle Society (AOFAS) hindfoot score were completed. In order to investigate the role of the underlying alignment on the aggravation of ankle osteoarthritis, patients were divided into a 'varus' and a 'valgus' group based on the indication for surgery.
The outcome scores (AOFAS and FFI) after triple arthrodesis remained stable in the present 7.5-year follow-up study. An important increase of OA of the ankle was not established, 58% of the patients showed no aggravation, 31% one-grade and 2% two-grade increase of OA. A trend was found (P=.063) towards aggravation of OA of the ankle in patients of the varus group with the highest medial arches (persistent cavovarus deformity).
Level II, retrospective study. | This study reports minor, not statistically significant, changes of the ankle joint following triple arthrodesis after 7.5 years. Clinical outcome remained stable in time. Clinical relevance It seems that triple arthrodesis as such does not lead to major osteoarthritis of the ankle, given that adequate alignment of the hindfoot is achieved. |
3,385 | 41,603 | The aim of this study was to develop a clinical-grade, automated, multiplex system for the differential diagnosis and molecular stratification of rheumatoid arthritis (RA).
We profiled autoantibodies, cytokines, and bone-turnover products in sera from 120 patients with a diagnosis of RA of < 6 months' duration, as well as in sera from 27 patients with ankylosing spondylitis, 28 patients with psoriatic arthritis, and 25 healthy individuals. We used a commercial bead assay to measure cytokine levels and developed an array assay based on novel multiplex technology (Immunological Multi-Parameter Chip Technology) to evaluate autoantibody reactivities and bone-turnover markers. Data were analyzed by Significance Analysis of Microarrays and hierarchical clustering software.
We developed a highly reproducible, automated, multiplex biomarker assay that can reliably distinguish between RA patients and healthy individuals or patients with other inflammatory arthritides. Identification of distinct biomarker signatures enabled molecular stratification of early-stage RA into clinically relevant subtypes. In this initial study, multiplex measurement of a subset of the differentiating biomarkers provided high sensitivity and specificity in the diagnostic discrimination of RA: Use of 3 biomarkers yielded a sensitivity of 84.2% and a specificity of 93.8%, and use of 4 biomarkers a sensitivity of 59.2% and a specificity of 96.3%. | The multiplex biomarker assay described herein has the potential to diagnose RA with greater sensitivity and specificity than do current clinical tests. Its ability to stratify RA patients in an automated and reproducible manner paves the way for the development of assays that can guide RA therapy. |
3,386 | 50,509 | To evaluate the results of glucosamine hydrochloride in the treatment of knee degenerative osteoarthritis (DOA).
From February 2006 to January 2007, 60 patients with knee DOA were treated with glucosamine hydrochloride, including 15 males and 45 females. The ages of patients ranged from 41 to 67 years with an average age of 57.5 years. The disease course ranged from 6 months to 3 years. Oral glucosamine hydrochloride was given twice a day, each 750 mg, for a 6-week course of treatment; another course of treatment was repeated after 4 months. After two courses of treatment, the international standard DOA score of Lequesne index was used to evaluate the rest of knee pain, sports pain, tenderness, joints activity, morning stiffness and walking ability.
All 60 patients finished treatment, various clinical symptoms for DOA disappeared completely in 31 cases and subsided in 27 cases; the cure rate was 51.7% and the total response rate was 96.7%. The scores of rest pain, sport pain, tenderness, joints activity, morning stiffness and the ability to walk for knee after treatment were 0.5+/-0.2, 0.7+/-0.4, 0.8+/-0.3, 0.9+/-0.4, 0.6+/-0.3 and 0.9+/-0.4, showing statistically significant differences (P<0.01) when compared with preoperation (1.6+/-0.5, 2.1+/-0.4, 2.2+/-0.5, 1.8+/-0.6, 1.7+/-0.4 and 2.0+/-0.4). Adverse effect occurred in 3 cases (5%) and the patients recovered without special treatment. | Glucosamine hydrochloride can cure knee DOA with symptom-relieving and joint function-improving action. |
3,387 | 24,118 | Although sagittal tibial alignment in total knee arthroplasty (TKA) is important, no landmarks exist to achieve a reproducible slope. The purpose of this study was to evaluate the clinical usefulness of the distance from the guide rod to the skin surface for the tibial slope in TKA.
Computer simulation studies were performed on 100 consecutive knees scheduled for TKA. The angle between the line connecting the most anterior point of the predicted tibial cut surface and the skin surface 20 cm distal to the predicted cut surface (Line S) and the mechanical axis (MA) of the tibia in the sagittal plane was measured.
The mean (±SD) absolute angle difference between the Line S and the MA was 0.9°±0.7°. The Line S was almost parallel to the MA in the sagittal plane (95% and 99% within two degrees and three degrees of deviation from MA, respectively).
II. | The guide rod orientation is a surrogate for the tibial cut slope because the targeted posterior slope is usually built into the cutting block and ensuring the rod is parallel to the MA in the sagittal plane is recommended. Therefore the distance between the skin surface and the rod can be a useful guide for the tibial slope. |
3,388 | 12,563 | CD14 is a monocyte/macrophage pattern-recognition receptor that modulates innate inflammatory signaling. Soluble CD14 levels in knee OA synovial fluids are associated with symptoms and progression of disease. Here we investigate the role of this receptor in development of OA using a murine joint injury model of disease.
10-week-old Male C57BL/6 (WT) and CD14-deficient (CD14-/-) mice underwent destabilization of the medial meniscus (DMM) surgery to induce OA. Joint histopathology was used to examine cartilage damage, and microCT to evaluate subchondral bone (SCB) remodeling at 6 and 19 weeks after surgery. Synovial and fat pad expression of macrophage markers (F4/80, CD11c, CD68, iNOS, CCR7, CD163 and CD206) was assessed by flow cytometry and droplet digital (dd)PCR. Changes in locomotive activity indicative of joint pain were evaluated longitudinally up to 16 weeks by automated behavioral analysis.
Early cartilage damage scores 6 weeks post-DMM were similar in both strains (Mean score ±SEM WT: 4.667±1.38, CD14-/-: 4.6±0.6), but at 19 weeks were less severe in CD14-/- (6.0±0.46) than in WT mice (13.44±2.5, p = 0.0002). CD14-/- mice were protected from both age-related and post-surgical changes in SCB mineral density and trabecular thickness. In addition, CD14-/- mice were protected from decreases in climbing activity (p = 0.015 vs. WT, 8 weeks) observed after DMM. Changes in synovial/fat pad expression of CCR7, a marker of M1 macrophages, were slightly reduced post-DMM in the absence of CD14, while expression of CD68 (pan-macrophage marker) and CD163 (M2 marker) were unchanged. | CD14 plays an important role in progression of structural and functional features of OA in the DMM model, and may provide a new target for therapeutic development. |
3,389 | 21,335 | Early identification of patients unlikely to achieve good long-term disease control with anti-tumor necrosis factor therapy in axial spondyloarthritis (SpA) and psoriatic arthritis (PsA) is important for physicians following treat-to-target recommendations. Here we assess associations between disease activity or clinical response during the first 12 weeks of treatment and attainment of treatment targets at week 48 in axial SpA and PsA patients receiving certolizumab pegol.
The relationship between disease activity or clinical response during the first 12 weeks of treatment and achievement of week-48 targets (for axial SpA: inactive disease based on Ankylosing Spondylitis Disease Activity Score [ASDAS] using the C-reactive protein [CRP] level, or Bath Ankylosing Spondylitis Disease Activity Index <2 with normal CRP level; and for PsA: minimal disease activity) was assessed post hoc using RAPID-axSpA and RAPID-PsA trial data.
A clear relationship between disease activity from week 2 to 12 and achievement of week-48 treatment targets was observed in both axial SpA and PsA populations. In axial SpA, week-48 ASDAS inactive disease was achieved by 0% of patients (0 of 21) with ASDAS very high disease activity at week 12, compared to 68% of patients (34 of 50) with week-12 ASDAS inactive disease. For PsA, week-48 minimal disease activity was achieved by 0% of patients (0 of 26) with Disease Activity Score in 28 joints (DAS28) using the CRP level >5.1 at week 12, compared to 73% of patients (57 of 78) with DAS28-CRP <2.6. Similar results were observed regardless of the disease activity measure used. Clinical response at week 12 also predicted week-48 outcomes, though to a lesser extent than disease activity. | Using disease activity and the clinical response state during the first 12 weeks of certolizumab pegol treatment, it was possible to identify a subset of axial SpA and PsA patients unlikely to achieve long-term treatment goals. |
3,390 | 3,341 | Adult-onset Still's disease (AOSD) is a severe autoinflammatory disease. Neutrophil activation with enhanced neutrophil extracellular trap (NET) formation is involved in the pathogenesis of AOSD. Functional leukocyte immunoglobulin-like receptor A3 (LIR-A3; gene name LILRA3) has been reported to be associated with many autoimmune diseases. We aimed to investigate the association of LILRA3 with disease susceptibility and neutrophil activation in AOSD.
The LILRA3 deletion polymorphism and its tagging single-nucleotide polymorphism rs103294 were genotyped in 164 patients with AOSD and 305 healthy controls. The impact of LILRA3 on clinical features and messenger RNA expression was evaluated. Plasma levels of LIR-A3 were detected using enzyme-linked immunosorbent assay (ELISA), and the correlation between LIR-A3 plasma levels and disease activity and levels of circulating NET-DNA was investigated. LIR-A3-induced NETs were determined using PicoGreen double-stranded DNA dye and immunofluorescence analysis in human neutrophils and a neutrophil-like differentiated NB4 cell line transfected with LIR-B2 small interfering RNA.
The findings from genotyping demonstrated that functional LILRA3 was a risk factor for AOSD (11% in AOSD patients versus 5.6% in healthy controls; odds ratio 2.089 [95% confidence interval 1.030-4.291], P = 0.034), and associated with leukocytosis (P = 0.039) and increased levels of circulating neutrophils (P = 0.027). Functional LILRA3 messenger RNA expression was higher in the peripheral blood mononuclear cells (P < 0.0001) and neutrophils (P < 0.001) of LILRA3 | Our study provides the first evidence that functional LILRA3 is a novel genetic risk factor for the development of AOSD and that functional LIR-A3 may play a pathogenic role by inducing formation of NETs. |
3,391 | 10,544 | To evaluate effects of daily cane use for 3 months on medial tibiofemoral bone marrow lesion (BML) volumes in people with medial tibiofemoral osteoarthritis (OA).
In this randomized controlled trial (RCT), 79 participants with medial tibiofemoral OA were randomized to either a cane group (using a cane whenever walking) or control group (not using any gait aid) for 3 months. The cane group received a single training session by a physiotherapist, using a biofeedback cane to teach optimal technique and body weight support and motor learning principles to facilitate retention of learning. The primary outcome was change in total medial tibiofemoral BML volume (per unit bone volume) measured from magnetic resonance imaging (MRI) at 3 months. Secondary outcomes were BML volumes (per unit bone volume) of the medial tibia and femur, and patient-reported outcomes of overall knee pain, knee pain on walking, physical function, perceived global symptom changes and health-related quality of life. MRI analyses were performed by a blinded assessor.
Seventy-eight participants (99%) completed the primary outcome. Mean (standard deviation) daily cane use was 2.3 (1.7) hours over 3 months. No evidence of between-group differences was found for change in total medial tibiofemoral BML volume (mean difference: -0.0010 (95% confidence intervals: -0.0022, 0.0003)). Most secondary outcomes showed minimal differences between groups.
Australian New Zealand Clinical Trial Registry (ACTRN12614000909628). | Daily use of a cane during walking for 3 months aiming to reduce knee joint loading did not change medial tibiofemoral BML volumes compared to no use of gait aids. |
3,392 | 32,515 | The purpose of this article is to compare lower limb length and alignment measurements on supine CT, upright full-length radiography, and 3D models based on upright biplanar linear radiography.
This study involved 51 consecutive patients (22 men and 29 women; mean age, 68.8 years; range, 43-92 years) who were scheduled for total knee replacement. Lower limb length and alignment angle were measured on CT, upright full-length radiography, and 3D models based on biplanar linear radiography with standard and composed leg methods by two independent readers. Descriptive statistics of each modality were calculated. Measurements of different modalities were compared by paired Student t tests. Agreement between readers and modalities was assessed by Bland-Altman analyses.
Mean (± SD) limb lengths were 783 ± 56.1 mm (range, 639-927 mm), 785 ± 53.0 mm (range, 655-924 mm), 780 ± 55.4 mm (range, 633-921 mm), and 783 ± 55.9 mm (range, 636-924 mm) for CT, upright full-length radiography, and 3D models based on biplanar linear radiography standard and composed leg measurements, respectively. Mean alignment angles were 2.3° ± 5.5° (range, -12° to 20°) for CT, 2.5° ± 6.7° (range, -17° to 18°) for upright full-length radiography, and 3.4° ± 6.6° (range, -14° to 18°) for 3D models based on biplanar linear radiography. No significant differences among modalities for mean limb length were found when using composed leg measurements in biplanar linear radiography. Very small but significant mean differences in angle measurements were seen for CT (-1.1° ± 2.5) and upright full-length radiography (-0.9° ± 3.1) compared with biplanar linear radiography. Bland-Altman analyses showed no significant differences between readers, with the highest agreement for biplanar linear radiography length measurements. | Measurements on 3D models based on upright biplanar linear radiographs allow lower limb length and alignment angle measurements that are interchangeable with supine CT scans and upright full-length radiographs but with superior interreader agreement. |
3,393 | 68,075 | To investigate whether low-dose cyclosporin A (CSA) is safe and effective in comparison with chloroquine (CQ) in patients with early rheumatoid arthritis (RA).
We performed a randomized, double-blind study comparing CSA with CQ in patients with early RA (duration < 2 years) who had had active disease for at least 3 months. Forty-four RA patients with a mean disease duration of 6 months were randomly allocated to receive CSA (initial dosage 2.5 mg/kg/day, maintenance dosage 3.6 mg/kg/day) or CQ (initial dosage 300 mg/day, maintenance dosage 100 mg/day) for 24 weeks.
Five patients (2 taking CSA and 3 taking CQ) discontinued the study prematurely. Intention-to-treat analysis disclosed a decrease in the swollen joint count by 7 in both groups. The erythrocyte sedimentation rate and C-reactive protein level did not change significantly. CSA and CQ were tolerated equally well, although mild paraesthesia occurred more frequently in the CSA-treated group. The serum creatinine level increased by 13 mumoles/liter (95% confidence interval [95% CI] 4, 22) in the CSA group and by 6 mumoles/liter (95% CI 1, 11) in the CQ group (difference not statistically significant). | Both CSA and CQ are effective in alleviating the symptoms of active early RA. There is only slightly impaired renal function after 24 weeks of drug administration of either drug in patients with early RA. |
3,394 | 16,819 | To assess the acute effect of resistance exercise (RE) on circulating biomarkers of cartilage breakdown and inflammation in women with rheumatoid arthritis (RA).
Thirty-four volunteers (17 with and 17 without RA), participated in a 25 min RE session (knee extension, knee flexion, hip abduction and hip adduction) with one set of 12 repetitions at 50% of one repetition maximum (1RM) and one set of eight repetitions at 75% of 1RM. Blood samples were collected 30 and 5 min before, immediately after and 1, 2 and 24 h after the session. We used analysis of variance for repeated-measures with Bonferroni adjustments to assess differences between groups over time.
In both groups we found significant changes in interleukin (IL)-1 beta (P = 0.045), IL-1 receptor antagonist (IL-1ra) (P < 0.001), IL-10 (P = 0.004), IL-6 (P < 0.001) and cartilage oligomeric matrix protein (COMP) P < 0.001) in response to exercise, but no changes in tumor necrosis factor-alpha and C-reactive protein levels. We found no differences in the responses of the two groups to the session, except for COMP levels, which are more sensitive to exercise and rest effects in RA patients. | Women with and without RA have similar changes in response to a RE session in levels of inflammation biomarkers, but not of cartilage breakdown. IL-10 and IL-1ra increased after the RE session, indicating that RE may have an acute anti-inflammatory effect. Additional studies are necessary to clarify if repeated RE sessions can have long-term anti-inflammatory effects and the possible clinical repercussions of this cartilage breakdown characteristic in response to exercise in RA patients. |
3,395 | 49,964 | To compare the composition of intestinal microbiota of patients with early rheumatoid arthritis (RA) or fibromyalgia (FM), fecal samples were collected from 51 patients with RA and 50 with FM.
RA patients fulfilled the RA criteria of the American College of Rheumatology, and duration of their disease was < or = 6 months. Only nonhospitalized patients from outpatient care were included. Patients having extreme diets or previous disease modifying antirheumatic drug or glucocorticoid medication were excluded, as were those taking antibiotics or having gastroenteritis for at least 2 months prior to sampling. Fecal bacterial composition was analyzed with a method based on flow cytometry, 16S rRNA hybridization, and DNA-staining. A set of 8 oligonucleotide probes was used.
In comparison to patients with FM, the RA patients had significantly less bifidobacteria and bacteria of the Bacteroides-Porphyromonas-Prevotella group, Bacteroides fragilis subgroup, and Eubacterium rectale--Clostridium coccoides group. Results from the 8 probes showed a significant overall difference between the 2 patient groups, indicating widespread microbial differences. | These findings support the hypothesis that intestinal microbes participate in the etiopathogenesis of RA. |
3,396 | 40,685 | To estimate the prevalence of overweight and obese Canadians with arthritis and to describe their use of arthritis self-management strategies, as well as explore the factors associated with not engaging in any self-management strategies.
Respondents to the 2009 Survey on Living with Chronic Diseases in Canada, a nationally representative sample of 4,565 Canadians age ≥20 years reporting health professional-diagnosed arthritis (including more than 100 rheumatic diseases and conditions), were asked about the impact of their arthritis and how it was managed. Among the overweight (body mass index [BMI] 25-29.9 kg/m(2)) and obese (BMI ≥30 kg/m(2)) individuals with arthritis (n = 2,869), the use of arthritis self-management strategies (i.e., exercise, weight control/loss, classes, and community-based programs) were analyzed. Log binomial regression analyses were used to examine factors associated with engaging in none versus any (≥1) of the 4 strategies.
More than one-quarter (27.4%) of Canadians with arthritis were obese and an additional 39.9% were overweight. The overweight and obese individuals with arthritis were mostly female (59.5%), age ≥45 years (89.7%), and reported postsecondary education (69.0%). While most reported engagement in at least 1 self-management strategy (84.9%), less than half (45.6%) engaged in both weight control/loss and exercise. Factors independently associated with not engaging in any self-management strategies included lower education, not taking medications for arthritis, and no clinical recommendations from a health professional. | Fewer than half of the overweight and obese Canadians with arthritis engaged in both weight control/loss and exercise. The provision of targeted clinical recommendations (particularly low in individuals that did not engage in any self-management strategies) may help to facilitate participation. |
3,397 | 37,097 | Collagen-induced arthritis (CIA) has traditionally been performed in MHC class II A(q)-expressing mice, whereas most genetically modified mice are on the C57BL/6 background (expressing the b haplotype of the major histocompatibility complex (MHC) class II region). However, C57BL/6 mice develop arthritis after immunisation with chicken-derived collagen type II (CII), but arthritis susceptibility has been variable, and the immune specificity has not been clarified.
To establish a CIA model on the C57BL/6 background with a more predictable and defined immune response to CII.
Both chicken and rat CII were arthritogenic in C57BL/6 mice provided they were introduced with high doses of Mycobacterium tuberculosis adjuvant. However, contaminating pepsin was strongly immunogenic and was essential for arthritis development. H-2(b)-restricted T cell epitopes on chicken or rat CII could not be identified, but expression of A(q) on the C57BL/6 background induced T cell response to the CII260-270 epitope, and also prolonged the arthritis to be more chronic. | The putative (auto)antigen and its arthritogenic determinants in C57BL/6 mice remains undisclosed, questioning the value of the model for addressing T cell-driven pathological pathways in arthritis. To circumvent this impediment, we recommend MHC class II congenic C57BL/6N.Q mice, expressing A(q), with which T cell determinants have been thoroughly characterised. |
3,398 | 26,359 | Three methods of surgery used in the treatment of knee osteoarthritis (OA) are mobile bearing unicompartmental knee arthroplasty (Oxford UKA), opening wedge high tibial osteotomy (HTO), and dome-type HTO. This article aimed to retrospectively compare these three methods in terms of outcomes for health status, patient satisfaction, and function.
Between 2003 and 2010, 255 knees of 235 patients underwent operations for medial knee OA. Three types of surgery were performed. Group 1 consisted of 109 knees of 94 patients who underwent Oxford UKA. Group 2 was made up of 36 knees of 36 patients who underwent HTO using circular external fixation, and Group 3 comprised 57 knees of 52 patients on whom opening wedge type HTO using locking plate fixation was performed. SF-36 and HSS knee scores were used to compare the functional outcomes among groups.
Statistically significant differences were found between the preoperative and postoperative measures in all 3 of the treatment groups for physical function, physical role, pain, general health, vitality, social function, emotional role, and mental health according to SF-36 and HSS scores. In the 2nd group, the average correction of the mechanical axis deviation (MAD) was 38 mm with 11.7º along the femorotibial axis and 6.2º along the medial proximal tibial angle (MPTA). In the 3rd group, the average correction in the MAD was 28 mm with 9.7º along the femorotibial axis and 5.6º along the MPTA. All 3 of the treatment alternatives were observed to be sufficient. Satisfactory postoperative results were achieved in the UKA group in terms of social function and mental health, and the patients were able to achieve early rehabilitation and return to their previous life activities. | UKA is the ideal option for patients who wish for the earliest possible return to social and recreational activities. |
3,399 | 4,675 | Little is known about potential mechanisms of action linking protective positive psychological variables and functional disability in patients with rheumatic and musculoskeletal disease. The present study was undertaken to examine symptoms of psychopathology, including stress, depression, anxiety, and sleep quality, as serial mediators of the association between gratitude, self-compassion, self-forgiveness, and functional impairment.
We assessed risk and protective factors for functional disability in patients with fibromyalgia (FM), osteoarthritis (OA), rheumatoid arthritis (RA), and ankylosing spondylitis (AS) who were recruited from an Austrian health care facility. Respondents completed online surveys, including the Gratitude Questionnaire 6-item form, the Self-Compassion Scale short form, the Self-Forgiveness and Forgiveness of Others Index, the Perceived Stress Scale 4, the Patient Health Questionnaire 2, the 2-item Generalized Anxiety Disorder Scale, the Sleep Condition Indicator, and the Health Assessment Questionnaire. Bivariate and serial mediation analyses were conducted.
For our sample of 1,218 patients (52% female, n = 632; AS [37%], OA [34%], RA [14%], and FM [24%]), stress, depression, and anxiety, in parallel as first-order mediators, and sleep quality as a second-order mediator, explained the association between positive psychological variables and functional disability. | Positive psychological factors exert a beneficial downstream effect on mental well-being, sleep health, and health-related functional impairment. Therapeutic promotion of gratitude, self-compassion, and self-forgiveness may improve mental and physical health in patients with rheumatic and musculoskeletal disease. |
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