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Although improvements are achieved by general exercise, training to improve sensorimotor control may be needed for people with osteoarthritis (OA). The aim was to apply the principles of neuromuscular training, which have been successfully used in younger and middle-aged patients with knee injuries, to older patients with severe hip or knee OA. We hypothesized that the training program was feasible, determined as: 1) at most acceptable self-reported pain following training; 2) decreased or unchanged pain during the training period; 3) few joint specific adverse events related to training, and 4) achieved progression of training level during the training period. Seventy-six patients, between 60 and 77 years, with severe hip (n = 38, 55% women) or knee OA (n = 38, 61% women) underwent an individualized, goal-based neuromuscular training program (NEMEX-TJR) in groups for a median of 11 weeks (quartiles 7 to 15) prior to total joint replacement (TJR). Pain was self-reported immediately after each training session on a 0 to 10 cm, no pain to pain as bad as it could be, scale, where 0-2 indicates safe, > 2 to 5 acceptable and > 5 high risk pain. Joint specific adverse events were: not attending or ceasing training because of increased pain/problems in the index joint related to training, and self-reported pain > 5 after training. The level of difficulty of training was registered. Patients with severe OA of the hip or knee reported safe pain (median 2 cm) after training. Self-reported pain was lower at training sessions 10 and 20 (p = 0.04) and unchanged at training sessions 5 and 15 (p = 0.170, p = 0.161) compared with training session 1. There were no joint specific adverse events in terms of not attending or ceasing training. Few patients (n = 17, 22%) reported adverse events in terms of self-reported pain > 5 after one or more training sessions. Progression of training level was achieved over time (p < 0.001).

The NEMEX-TJR training program is feasible in patients with severe hip or knee OA, in terms of safe self-reported pain following training, decreased or unchanged pain during the training period, few joint specific adverse events, and achieved progression of training level during the training period.

To compare torque-angle characteristics of the knee extensors of women with and without osteoarthritis (OA) of the knee, and to determine the reliability of these measures. The isometric torque of the knee extensors of both legs was tested on 3 occasions in 17 women with OA of the knee and 17 healthy women. Tests were performed on an isokinetic dynamometer at 3 knee angles (30 degrees, 60 degrees, 90 degrees). The peak torque values were subjected to 4 way analysis of variance (group vs leg vs angle vs time), and intraclass correlation coefficients were calculated. The reliability coefficients for repeated measures of isometric torque varied from 0.83 to 0.94 in the OA group and from 0.90 to 0.95 in the comparison group. The ANOVA and post hoc analyses revealed that the OA group had significantly (p < 0.05) lower knee extensor torque than the comparison group, and that the more symptomatic OA knee had lower torque than the contralateral limb. The torque was different across the 3 angles, but the torque-angle relationship was the same for both groups.

Isometric torque of the knee extensors can be measured reliably in women with OA of the knee. The torque is lower in women with OA than in women with no knee problems, and the changes are similar across different knee angles.

Rheumatological manifestations (RM) are very common in human immunodeficiency virus (HIV)-infected patients. The aim of this study was to determine the clinical spectrum of musculoskeletal involvement and relationship with the Centers for Disease Control and Prevention (CDC) stage and CD4+ cells and other factors. A cross-sectional study was conducted involving 75 patients of over 18 years of either sex with confirmed HIV status attending a tertiary care hospital in north India in one calendar year. Baseline demographic details, relevant history including duration of combination antiretroviral therapy (cART), RM, joints involved, CD4 cell count, and biochemical parameters were evaluated. Of 75 patients, 54 were male and 21 were female (mean age 33.15 ± 5.00 years, range 21-48 years). Most common RM was arthralgia (26.67%), followed by myalgia (18.67%), and arthritis (13.33%). Keratoderma blennorrhagicum (1.33%), tendo-achilles tendinitis (2.67%), and plantar fasciitis (2.67%) were other manifestations. Spondyloarthritis (SpA) was seen in 8% patients (undifferentiated SpA 4%, reactive arthritis 2.67%, psoriatic arthritis 1.67%). HIV-associated arthritis was seen in 2.67% while septic arthritis, rheumatoid arthritis, vasculitis, and diffuse infiltrative lymphocytic syndrome were seen in one patient (1.33%) each. The mean duration of disease in patients with RM was significantly less than patients without RM (p < 0.01). The erythrocyte sedimentation rate in patients with RM was significantly higher than in patients without RM (p < 0.05). Mean CD4 + cells were also significantly lower in patients with RM as compared to patients without RM (p < 0.05). Significantly fewer patients on cART had RM in comparison to patients not on cART (p < 0.001). Of 35 patients with RM,  25 were in CDC stage IV.

RM are common in HIV-infected patients. HIV arthralgia, myalgia, and undifferentiated SpA are the common manifestations. RM were associated with low CD4 counts. Most of the cases with RM were in CDC stage IV.

The incidence of many chronic diseases is increasing rapidly in South Korea. Rheumatoid arthritis is a chronic disease for which treatment by both doctors and long-term self-care by patients is deemed very important for successful disease management. This study is designed to examine and identify the factors influencing self-care competence in Korean women with rheumatoid arthritis. A cross-sectional descriptive design was employed. Participants included 132 women aged 20 years or older who were visiting rheumatoid arthritis outpatient clinics at hospitals in Seoul and Gyeonggi-do, South Korea. Measures included a demographics form, Self-as-Carer Inventory, Korean Activities of Daily Living scale, Visual Analogue Scale, Mishel Uncertainty in Illness Scale-Community Form, and Self-esteem Scale. The analyses illustrated the significance of the prediction model (F = 21.744, p < .001). The value of the adjusted R was set at .401, corresponding to 40.1% explanatory power. Uncertainty (β = -.43) and self-esteem (β = .26) were identified as having the most influence on self-care competence in Korean women with rheumatoid arthritis.

This cross-sectional study yielded preliminary evidence that nursing interventions that reduce uncertainty and improve self-esteem in Korean women with rheumatoid arthritis are necessary to promote the self-care competence of this vulnerable population. Healthcare professionals should recognize uncertainty and self-esteem as factors that influence self-care competence in Korean women with rheumatoid arthritis.

To evaluate the effect of atorvastatin (liprimar) on the laboratory values of inflammation and blood lipid composition in rheumatoid arthritis (RA) patients with no history of cardiovascular diseases (CVD). Subjects and methods. Fifty women with grade II RA activity according to DAS28 and radiologic (erosive) Stages I-III were examined; the patients were not former or current smokers; all were seropositive; their mean age was 50.2±9.9 years. All the patients with RA were divided into 2 groups: Group 1 took no atorvastatin and continued to receive standard previously prescribed therapy; Group 2 used atorvastatin in a dose of 20 mg. Lipidogram readings and the levels of Apo-A and Apo-B, neopterin, tumor necrosis factor-α, C-reactive protein, sP-selectin, sE-selectin, interleukin (IL)-6, IL-10, IL-12, and matrix metalloproteinases 3 and 9 were assessed. The patients with RA show obvious blood lipid composition impairments. Incorporation of atorvastatin (liprimar) into combination therapy for RA not only causes a considerable reduction in total cholesterol, low-density lipoprotein cholesterol, triglycerides, and apo-B levels, but also positively affects the inflammatory activity of the disease, by lowering the level of proinflammatory cytokines and increasing that of the anti-inflammatory cytokine IL-10. Цель исследования. Оценка влияния аторвастатина (липримар) на лабораторные показатели воспаления и липидного состава крови у пациентов с ревматоидным артритом (РА) без сердечно-сосудистых заболеваний (ССЗ) в анамнезе. Материалы методы. Обследовали 50 женщин с РА II степени активности заболевания по индексу DAS28 со II-III рентгенологической стадией (эрозивной), пациентки не курили ни в прошлом, ни в настоящем, все серопозитивны, средний возраст 50,2±9,9 года. Всех пациенток с РА разделили на 2 группы: 1-я не получала аторвастатин и продолжала принимать стандартную, ранее назначенную терапию, 2-й группе назначен аторвастатин в дозе 20 мг. Оценивали показатели липидограммы, уровни Апо-А и Апо-В, неоптерина, α-фактора некроза опухоли, С-реактивного белка, sP-селектина, sЕ-селектина, интерлейкинов (ИЛ) 6, 10, 12, матриксных металлопротеиназ-3 и 9. Результаты. Пациентки с РА характеризуются выраженными нарушениями липидного состава крови. Включение в комплексную терапию больных РА аторвастатина (липримар) не только способствует значительному снижению уровней общего холестерина, холестерина липопротеидов низкой плотности, триглицеридов, апо-В, но и положительно влияет на воспалительную активность заболевания, снижая уровень провоспалительных цитокинов, увеличивая уровень противовоспалительного цитокина ИЛ-10 Заключение. Указанные изменения могут лежать в основе профилактики осложнений ССЗ у больных РА.

The above changes may underlie the prevention of CVD complications in patients with RA.

To investigate the association between gout and myocardial infarction (MI) in a representative cohort in Taiwan. Data were collected from the Taiwan National Health Insurance database. Adults >20 years of age without history of MI were included. Patients were considered to have gout if they received a diagnosis of gout requiring medical treatment. Multivariate Cox proportional hazards models were used to evaluate the risk of MI in gout patients. Of the 704 503 patients included, 26 556 (3.8%) had gout. In total, 3718 (with gout, n = 463; without gout, n = 3255) patients had an MI, 299 (with gout, n = 35; without gout, n = 264) of whom died. The incidence of MI was 2.20 and 0.60 per 1000 patient-years in individuals with and without gout, respectively (log-rank test, P < 0.001). After adjustment for age, sex and history of diabetes mellitus, hypertension, coronary heart disease (CHD), stroke and end-stage renal disease, gout was associated with MIs [hazard ratio (HR), 1.23] and non-fatal MIs (HR, 1.26). In individuals without cardiovascular risk factors, gout was associated with MIs (HR 1.84; 95% CI 1.51, 2.24) and non-fatal MIs (HR 1.80; 95% CI 1.49, 3.95), after adjustment for age and sex. Moreover, in our study population, the HRs for MI decreased as age increased.

Gout is an independent risk factor for MI, and the increased risk of MI is present even in young people and those without cardiovascular risk factors.

To compare the progression of biochemical biomarkers of osteoarthritis (OA), knee pain, and function between nonobese patients (NON), obese patients without depression (OBESE), and obese patients with comorbid depression (O + D). Utilizing the FNIH OA Biomarkers Consortium dataset, we categorized knee OA patients into NON, OBESE, and O + D groups based on body mass index and Center for Epidemiological Studies-Depression (CES-D) scores. Subjective symptoms (Knee injury and Osteoarthritis Outcome Score Quality of Life subscale (KOOS QOL), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain and Physical Function scores, and the Short Form-12 (SF-12) Physical Component Score [PCS]) and objective measures of cartilage degradation and bone remodeling (urinary CTXII and CTXIα) were compared among groups at baseline and 2-year follow-up. Of the 600 patients, 282 (47%) were NON, 285 (47.5%) OBESE, and 33 (5.5%) O + D. The O + D group had significantly worse pain and function both at baseline and 2-year follow-up (

The combination of inferior knee pain, physical function, and significantly greater increases in biomarkers of cartilage degradation and bony remodelling suggest a more rapid progression for obese OA patients with comorbid depression. The link between systemic disease, inflammatory burden, and progressive cartilage degradation is in line with increasing concerns about a degenerative synovial environment in early osteoarthritic knees that progress to treatment failure with biologic restoration procedures.

Interleukin (IL)-6 -/- mice develop spontaneous mature onset obesity, while the influence of the pharmacological blockade of IL-6 on body weight in humans has not been previously reported. The aim of the present study was to observe weight change in patients treated with tocilizumab (TCZ). Twenty-one consecutive patients who started new treatment with TCZ were enrolled in the study. Sixteen consecutive patients who started treatment with infliximab (IFX) formed the control group. Height and weight of all patients were registered and Body Mass Index (BMI) calculated before the first treatment and at week 16. The Mann-Whitney or paired Wilcoxon test were used for comparisons between or within groups, respectively. The study demonstrated that treatment with TCZ was accompanied with significant weight gain and BMI increase (p=0.04), while IFX treatment did not result in any significant weight change during the 16-week period.

Weight gain can be seen in some patients during the pharmacological blockade of IL-6. The phenomenon and metabolic pathways involved should be further investigated.

To study the clinical profile of various subtypes of juvenile rheumatoid arthritis (JRA) in adulthood and analyse the outcome of the disease in terms of functional status, educational achievement, growth abnormalities, radiological progression and activity of the disease. From a group of 150 JRA cases, 26 adult patients were included in the study. All of them were under follow up since the onset of disease in childhood. Clinical data at the onset were obtained from old medical documents. Detailed clinical and laboratory assessment of all cases were done. There were 10 oligoarticular, 13 polyarticular and three systemic onset cases. Mean age of onset of disease was 11.7 +/- 3.39 years (range 2-15). Mean duration of follow up was 11.4 +/- 4.46 years range (6-22). Twenty-one patients had active disease. Ninety percent of oligoarthritis group were in class 1 status whereas none of the systemic onset JRA cases were in class I. Micrognathia, short stiff neck and short stature were noticed among polyarticular and systemic onset JRA. Seventy percent of oligoarthritis group developed inflammatory low back ache. Bony ankylosis of tarsal and carpal bones were seen in eight cases.

In our study there is a male predominance in JRA. Pauciarticular (oligoarthritis) JRA occurring in older boys had the best functional outcome. Growth abnormalities and radiological changes were more common in polyarticular and systemic onset JRA.

MTX is a prodrug producing anti-arthritic effects through a folylpolyglutamate synthase-mediated activation to MTX polyglutamates (MTXPGs). Our objective was to characterize the pharmacokinetics of intracellular MTXPGs and the factors associated with their accumulation in adult RA patients treated with MTX weekly. MTX pharmacokinetics were evaluated in 47 MTX-naïve patients enrolled in an MTX dose-escalation study for an average of 20 weeks and 223 patients enrolled in a cross-sectional study under long-term MTX therapy. Short-chain (MTXPG1-2), long-chain (MTXPG3) and very long-chain (MTXPG4-5) concentrations were measured in circulating red blood cells using liquid chromatography. Statistical analyses consisted of non-linear mixed models, multivariate regression analyses and Wilcoxon signed-rank test. The accumulation of MTXPG1-5 was sigmoidal and steady-state concentrations were achieved after 7 weeks of therapy. However, additional exposure and MTX dosage escalation produced a selective redistribution towards longer chain MTXPGs at the expense of shorter chain MTXPGs. Age, glomerular filtration rate and route of MTX administration were the most important predictors of MTXPG accumulation. In 10 patients, a switch from oral to parenteral MTX was associated with a 37% increase in long-chain MTXPGs, a 132% increase in very long-chain MTXPGs and a concomitant 31% reduction in disease activity (P<0.02).

The selective emergence of long-chain MTXPGs is function of dose, time of exposure and hence dosage intensity. Switching from oral to parenteral MTX produces a selective accumulation of longer chain MTXPGs that are known to be more potent inhibitors of de novo purine biosynthesis than shorter chain MTXPGs.

Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) affect individuals older than 50 years of age and corticosteroids are the mainstay of treatment. The aim of our study was to explore the role of leflunomide as a corticosteroid-sparing agent in GCA and PMR patients. Patients with difficult-to-treat GCA and PMR were retrospectively identified in the period from 2010 to 2013. The doses of corticosteroids and CRP values were noted before, after three months, and at the end of the treatment with leflunomide (for patients continuing treatment, censoring date was January 1, 2013). Twenty-three patients were identified (12 with PMR and 11 with GCA). A reduction of 6 mg/dL (CI 95% -10.9-34.2, P = 0.05) in CRP and 3.7 mg (CI 95% 0.5-7.0, P = 0.03) in prednisolone dose was observed in the PMR group. In GCA patients, the reduction was 12.4 mg/dL (CI 95% 0.7-25.5, P = 0.06) in CRP and 6.6 mg (CI 95% 2.8-10.3, P < 0.01) in prednisolone dose.

Leflunomide seems to be effective as a corticosteroid-sparing agent in patients with difficult-to-treat GCA and PMR. Randomized controlled trials are warranted in order to confirm the usefulness of leflunomide in the therapy of GCA/PMR.

To determine (1) if Medial Thrust or Trunk Lean reduces the knee adduction moment (EKAM) the most during gait in patients with medial knee osteoarthritis, (2) if the best overall strategy is the most effective for each patient and (3) if these strategies affect ankle and hip kinetics. Thirty patients with symptomatic medial knee osteoarthritis underwent 3-dimensional gait analysis. Participants received verbal instructions on two gait strategies (Trunk Lean and Medial Thrust) in randomized order after comfortable walking was recorded. The peaks and impulse of the EKAM and strategy-specific kinematic and kinetic variables were calculated for all conditions. Early stance EKAM peak was significantly reduced during Medial Thrust (-29%). During Trunk Lean, early and late stance EKAM peak and EKAM impulse reduced significantly (38%, 21% and -25%, respectively). In 79% of the subjects, the Trunk Lean condition was significantly more effective in reducing EKAM peak than Medial Thrust. Peak ankle dorsi and plantar flexion, knee flexion and hip extension and adduction moments were not significantly increased.

Medial Thrust and Trunk Lean reduced the EKAM during gait in patients with knee osteoarthritis. Individual selection of the most effective gait modification strategy seems vital to optimally reduce dynamic knee loading during gait. No detrimental effects on external ankle and hip moments or knee flexion moments were found for these conditions.

This study aimed to evaluate the validity of proximal fibular anatomic landmarks for measuring the coronal tibial mechanical axis in patients with knee osteoarthritis and to investigate individual factors associated with their reliability. A total of 106 knees in 96 patients were retrospectively reviewed. The angles between the tibial mechanical axis and fibular shaft axis (TFA), medial cortex of the proximal fibular shaft (MTA), and lateral cortex of the proximal fibular shaft (LTA) were measured from full-leg standing digital anteroposterior radiographs. An angle within three degrees was considered reliable. The association between the above three angles and individual factors, such as age, sex, body mass index (BMI), and varus-valgus knee malalignment, was determined to investigate individual factors associated with their reliability. The median TFA, MTA, and LTA were 1.52°, 1.56°, and 2.62°, respectively. The reliability rates of TFA, MTA, and LTA were 73.6% (95% CI: 65.19-81.98%), 82.1% (74.77-89.38%), and 58.5% (49.11-67.87%), respectively. The reliability of TFA and MTA was not associated with individual variables. The reliability of LTA was associated with BMI. Among patients with BMI greater than 25.3 kg/m

The fibular shaft axis and medial cortex of the proximal fibular shaft are reliable landmarks of the mechanical axis of the tibia. However, the reliability of the lateral cortex of the proximal fibular shaft is less satisfactory, especially in patients with BMI less than 25.3 kg/m

The development of osteoarthritis (OA) in the hand results in increased joint stiffness, which in turn affects the grip strength. The goal of the present study is to theoretically analyze the muscle forces in a thumb in response to the increased joint stiffness. The thumb was modeled as a linkage system consisting of a trapezium, a metacarpal bone, a proximal and a distal phalanx. Nine muscles were included in the model: flexor pollicis longus (FPL), extensor pollicis longus (EPL), extensor pollicis brevis (EPB), abductor pollicis longus (APL), flexor pollicis brevis (FPB), abductor pollicis brevis (APB), the transverse head of the adductor pollicis (ADPt), the oblique head of the adductor pollicis (ADPo), and opponens pollicis (OPP). Numerical tests were performed using an inverse dynamic approach. The joints were prescribed to an angular motion at one degree-of-freedom (DOF) each time with all other DOFs of the joints being mechanically constrained, while the muscle forces in response to the joint motions were predicted. The normal joint stiffness was assumed to be 0.05, 0.10, and 0.15 N m/rad for interphalangeal (IP), metacarpophalangeal (MCP), and carpometacarpal (CMC) joint, respectively. The joint stiffness was assumed to increase by 50% and 100%, simulating the biomechanical consequences of OA. Our simulations indicated that the increase in joint stiffness induced substantial increases in muscle forces, especially in the EPL and FPL muscles in response to IP, MCP, or CMC extension/flexion motions.

Because the strength of the muscles in the fingers is limited, the muscles will not be able to overcome joint resistance if joint stiffness is increased to its limit due to OA. This may contribute to the reduced range of motion typically seen in OA.

To assess inter-observer reliability in US detection of tendon inflammatory and structural changes at wrists and ankles in RA patients. Fourteen consecutive RA patients underwent bilateral US assessment of the extensor carpi ulnaris (ECUT) and tibialis posterior tendons (TPTs) by two blinded rheumatologists, with different level of experience in musculoskeletal (MS) US. Grey scale and power Doppler (PD) US assessment was focused on detection of tenosynovitis, tenosynovial and intra-tendon PD signal and structural lesions (i.e. tendinosis, tendon erosion, partial or total rupture). The frequency of US findings detected by Investigator 1 was 28.6% for inflammatory changes and 51.8% for structural damage changes while Investigator 2 detected 34 and 53.6% for the corresponding abnormalities. A high overall agreement (82.7%) was found for inflammatory pathology and 89.7% for structural lesions in all tendons. Mean kappa (κ) values for all tendons and pathology was moderate (κ = 0.42), with fair level of agreement for the wrist region (0.27-0.34) and moderate to good values for the ankle region (κ = 0.47-0.62). Subclinical abnormalities were detected in 37.5% of the tendons by Investigator 1 and 28.6% of the tendons by Investigator 2.

MSUS showed high overall agreement and fair to moderate inter-observer κ-values between investigators with different levels of experience in detection of tendon pathology at the wrist and ankle in RA patients. Further standardization of scanning method and pathology definitions may improve MSUS reproducibility.

To independently confirm previous probe drug findings that patients with rheumatoid arthritis (RA) have defective oxidation of cysteine derivatives. Measurement of cysteine dioxygenase substrate (cysteine) and product (sulfate) under controlled conditions, with elemental assessment by proton induced x-ray emission (PIXE). Plasma inorganic sulfate was significantly depressed in patients with rheumatoid arthritis (RA) compared to both controls and non-RA disease, 85 +/- 36 nm/ml vs 267 +/- 146 and 604 +/- 412 (mean +/- SD. RA patients vs non-RA disease p < 0.001). Fasting cysteine levels were significantly raised compared to controls (59 +/- 20 nm/ml vs 17 +/- 81 nm/ml p < 0.001). Synovial fluid (SF) sulfate was also significantly reduced in patients with RA compared to non-RA controls (202 +/- 117 nm vs 1041 +/- 700 p < 0.001). PIXE data confirmed the low sulfate levels in serum and SF while showing no reduction in the levels of other elements analyzed.

These cysteine/sulfate findings confirm the validity of the previous probe drug abnormalities and the importance of defective cysteine dioxygenase activity in RA.

This study aimed to evaluate the anthropometry of resected distal femurs in valgus knees at the level of standard cuts during total knee arthroplasty (TKA), and to compare these measurements to neutrally aligned knees. Anteroposterior and mediolateral measurements of the distal femur were performed on three-dimensional computed tomography reconstructions of 57 valgus knees (34 intra-articular valgus and 23 juxta-articular valgus) and 40 neutrally aligned knees. The measured dimensions and calculated aspect ratios (ARs) were subsequently compared. Juxta-articular valgus knees had similar ARs when compared with neutrally aligned knees (1.14 ± 0.06 vs. 1.12 ± 0.05, P = 0.103). However, intra-articular valgus knees had smaller ARs (1.09 ± 0.07) when compared with juxta-articular valgus (P = 0.002) or neutrally aligned knees (P = 0.023).

Different origins of valgus deformity in the femur can significantly affect the AR values on the resected surface of the distal femur. Pre-operative evaluation of a valgus deformity may assist in estimating the morphology of the resected distal femur during TKA.

To explore and understand how patients with knee osteoarthritis (OA) experience moxibustion. This qualitative research was conducted as part of a larger clinical trial of the effectiveness of moxibustion for the treatment of knee OA by qualitative content analysis. Sixteen patients with mild knee OA who participated in a 12-week moxibustion treatment as part of the trial were interviewed using open-ended questions. The participants recognised knee OA as a normal ageing process that caused physical and emotional discomfort in daily life. Regardless of any adverse effects of moxibustion, most of the participants were interested in continuous moxibustion treatment as a long-term management strategy and for general health.

This study suggests that moxibustion can be helpful in managing symptoms related to knee OA. Patients' attitudes towards moxibustion can affect the treatment result and those who prefer it want to continue the treatment for a long time because they understand that knee OA is a chronic condition which needs continuous care. However, practitioners need to pay more attention to those who are very enthusiastic because they tend to endure treatment-related adverse events in their desire for better effects.

Patient compliance is considered necessary for the success of drug treatment in chronic diseases. We document compliance with drug treatment and the factors affecting it in a cohort of patients with rheumatoid arthritis (RA). A prospective cohort study of 556 patients with RA followed for 3 years in 4 counties: Oslo, Norway; Groningen, The Netherlands; and Nancy and Reims, France. Compliance to treatment was assessed annually by interview in terms of adherence to the dose and timing of the prescribed drug regimen. Of the 556 subjects, 429 (77.2%) were taking medication for RA throughout the observation period. Consistent behavior was recorded in 59.5% of cases: 35.7% were consistently compliant, and 23.8% consistently noncompliant. Factors significantly associated with good compliance were older age (p = 0.00), female sex (p = 0.03), decreased disability (p = 0.04), very satisfactory contacts with health care professionals (p = 0.03), and more personal knowledge about the disease and its treatment (p = 0.03).

This longitudinal study identified compliance behavior as consistent over time in 60% of patients, determined by quality of contact with professionals and the amount of patient information available.

To relate serum leptin levels to prevalent and incident radiographic knee osteoarthritis (OA) and to determine if patterns of change in longitudinal serum leptin measures differ by knee OA status over a 10-year period. Participants in the Michigan Study of Women's Health Across the Nation underwent bilateral knee radiographs at baseline and followup visits 2, 4, and 11 for ascertainment of knee OA status (Kellgren/Lawrence score ≥2). Serum leptin measures were available from baseline and followup visits 1 and 3-7. The baseline prevalence of knee OA (mean age 46 years) was 18%; the 2-year incidence of knee OA at followup visits 2 and 4 was 18% and 14%, respectively. Serum leptin levels were associated with prevalent and incident knee OA. A 5 ng/ml increase in serum leptin level was associated with 38% higher odds of prevalent knee OA (odds ratio [OR] 1.38, 95% confidence interval [95% CI] 1.26-1.52) and 31% greater odds of incident knee OA (OR 1.31, 95% CI 1.21-1.41) after adjustment for covariates, including body mass index residuals. Leptin levels increased with time; on average, serum leptin levels increased by 0.38 ng/ml per year (P = 0.0004). Women with incident knee OA during the 10-year followup period had consistently higher serum leptin levels as compared to women with no knee OA during followup.

Our findings support a metabolic role of obesity in knee OA. A better understanding of the mechanisms by which increased fat mass is associated with joint damage is needed. Management of cardiometabolic dysfunction, including elevated serum leptin levels, may be beneficial in forestalling the onset or progression of knee OA.

To investigate the efficacy and tolerability of sulfasalazine (SSZ) in the treatment of early rheumatoid arthritis (RA). Eighty patients (symptomatic disease < 12 months) were randomly assigned to treatment with SSZ or placebo for 48 weeks. Clinical, laboratory, and scintigraphic data were used to determine the effects of treatment. SSZ was superior to placebo in reducing the laboratory features of inflammation, the clinical parameters of disease activity, as well as the scintigraphic activity in the joints. Furthermore, fewer erosive changes developed in the joints of patients receiving active treatment, but the difference between treatment groups did not reach statistical significance.

SSZ is effective in the treatment of RA, and its onset of action is rapid. The results support the view that SSZ retards the development of joint erosions. However, like other conventional disease-modifying antirheumatic drugs, its remission-inducing ability is insufficient.

To demonstrate the pharmacokinetic equivalence of CT-P13 and its innovator infliximab (IFX) in Japanese patients with rheumatoid arthritis (RA), and to compare the efficacy and safety of these drugs, administered for 54 weeks. In a randomized, double-blind, parallel-group, multicenter study, 3 mg/kg of CT-P13 or IFX, in combination with methotrexate (MTX) (6-16 mg/week), was administered for 54 weeks to Japanese active RA patients with an inadequate response to MTX, to demonstrate the pharmacokinetic equivalence, based on the area under the curve (AUC(τ)) (weeks 6-14) and C(max) (week 6) of these drugs, and to compare their efficacy and safety. The CT-P13-to-IFX ratios (90% confidence intervals) of the geometric mean AUC(τ) and C(max) values in patients negative for antibodies to infliximab at week 14 were 111.62% (100.24-124.29%) and 104.09% (92.12-117.61%), respectively, demonstrating the pharmacokinetic equivalence of these drugs. In the full analysis set, CT-P13 and IFX showed comparable therapeutic effectiveness, as measured by the American College of Rheumatology, Disease Activity Score in 28 joints, the European League Against Rheumatism, and other efficacy criteria, at weeks 14 and 30. The incidence of adverse events was similar for these drugs.

CT-P13 and IFX, administered at a dose of 3 mg/kg in combination with MTX to active RA patients, were pharmacokinetically equivalent and comparable in efficacy and safety.

Rheumatoid arthritis is an inflammatory disease with high incidence of cardiovascular disease due to accelerated atherosclerosis. Osteoprotegerin (OPG) has been associated with increased risk of atherosclerotic disease in the general population. Several polymorphisms in the OPG gene with functional effects on cardiovascular disease in non-rheumatic individuals have been described. Therefore, we aimed to analyze the effect of three of these functional OPG polymorphisms on the risk of cardiovascular disease in a large and well-characterized cohort of Spanish patients with rheumatoid arthritis. Three OPG gene variants (rs3134063, rs2073618 and rs3134069) were genotyped by TaqMan assays in 2027 Spanish patients with rheumatoid arthritis. Anti-cyclic citrullinated peptide (anti-CCP) antibody testing was positive in 997 of 1714 tested. Also, 18.3% of the whole series had experienced cardiovascular events, including 5.4% with cerebrovascular accidents. The relationship between OPG variants and cardiovascular events was assessed using Cox regression. No association between OPG gene variants and cardiovascular disease was observed in the whole group of rheumatoid arthritis patients or in anti-CCP positive patients. Nevertheless, a protective effect of CGA haplotype on the risk of cardiovascular disease in general, and specifically in the risk of cerebrovascular complications after adjusting for sex, age at disease diagnosis and traditional cardiovascular risk factors was disclosed in anti-CCP negative patients (HR = 0.54; 95%CI: 0.31-0.95; p = 0.032 and HR = 0.17; 95%CI: 0.04-0.78; p = 0.022, respectively).

Our results indicate a protective effect of the OPG CGA haplotype on cardiovascular risk, mainly due to a protective effect against cerebrovascular events in anti-CCP negative rheumatoid arthritis patients.

High tibial osteotomy and unicompartmental knee arthroplasty are surgical treatment options for unicompartmental knee arthritis; these procedures are indicated for patients who do not have severe arthritis in the lateral compartment. Valgus stress radiographs sometimes are used to make this evaluation, but this test has not been critically evaluated. We sought to determine (1) whether valgus stress radiographs help to evaluate the integrity of the cartilage in the lateral compartment in patients undergoing TKA for noninflammatory arthritis, and (2) whether valgus stress radiographs can identify patients whose varus deformity is correctable. We reviewed preoperative hip-to-ankle standing radiographs, AP standing radiographs, and valgus stress radiographs of 84 patients (91 knees) who underwent TKA for varus knee arthritis between July 2010 and January 2012. Valgus stress radiographs were obtained with the patient supine with the knee 20° flexed and a firm manual valgus force was applied through the knee. On valgus stress radiographs, the lateral compartment joint space width and the corrected mechanical alignment were measured. Intraoperative cartilage assessment (Outerbridge grade) was compared with lateral compartment joint space width. Knees with mechanical leg alignment of 3° varus to 3° valgus on valgus stress radiographs were considered correctable deformities. The lateral compartment joint space width on valgus stress radiographs did not correlate with the intraoperative Outerbridge grading of the lateral compartment cartilage (rs = -0.154; p = 0.146). The majority of knees (93%; 55 of 59) with 10° or less mechanical varus on hip-to-ankle standing radiographs were correctable within the range of 3° varus to 3° valgus.

Valgus stress radiographs provided no added benefit to the radiographic assessment of the lateral compartment cartilage and regarding the correctability of the varus deformity.

To evaluate superoxide anion (O2-), nitrite/nitrate (NO2-/NO3-), and nitrotyrosine (NT) production and the contribution of myeloperoxidase (MPO) to the production of NT-containing proteins in the synovial fluid (SF) of patients with juvenile idiopathic arthritis (JIA). The affected tissues in inflammatory arthritis produce large amounts of nitric oxide (NO) or peroxynitrite (ONOO-) but there are no reports of NO or ONOO- participation in JIA. We also attempted to correlate our findings with variables of disease activity and articular damage. We analyzed 40 patients with JIA, mean age 12.7 years, mean disease duration 7.8 years. O2- production was measured by cytochrome C reduction after incubation of 106 synovial fluid (SF) cells with or without phorbol myristate acetate (PMA), formyl-methionyl-leucyl-phenylalanine (FMLP) or opsonized zymosan. SF and serum NO2-/NO3- levels were measured by Griess reaction; NT was detected by Western blot. Myeloperoxidase (MPO) activity was estimated spectrophotometrically. Clinical and laboratory variables [erythrocyte sedimentation rate, C reactive protein (CRP), and radiological score] and interleukin 6 (IL-6) levels were evaluated. NO2-/NO3- production was greatly enhanced in the joints of JIA patients (54.6 +/- 3.2 micro M) when compared with serum (13.9 +/- 0.6 micro M; p < 0.001). NO2-/NO3- levels in SF were positively correlated with the number of infiltrating lymphomononuclear cells. NT-modified proteins detected in the SF showed a high correlation with radiological score, disease duration, CRP, and IL-6.

Our results confirm the increased oxidative stress in children with JIA, suggesting a high in situ production of NO. The positive correlation between the expression of NT-modified proteins and variables of disease activity and damage is additional evidence that nitrogen and oxygen species may be involved in the joint destruction seen in patients with JIA.

To obtain preliminary information about the effectiveness of intra-articular injections of an autologous preparation rich in growth factors (PRGF) for knee OA treatment to be explored further in future studies. We have characterized PRGF treatment by platelet count and concentration of relevant growth factors (TGF-Beta1, PDGF-AB, VEGF-A; HGF and IGF-I) involved in healing mechanisms. We have performed an observational retrospective cohort study using hyaluronan injections as a control. Each group included 30 patients with OA of the knee, matched according to age, sex, body mass index and radiographic severity. Both treatments were based on three weekly injections. Clinical outcome was examined using the WOMAC questionnaires prior to treatment and at 5 weeks after treatment. The observed success rates by week 5 for the pain subscale reached 33.4% for the PRGF group and 10% for the hyaluronan group. The difference was attributed exclusively to the treatment modality, p = 0.004. The percent reductions in the physical function subscale and overall WOMAC at 5 weeks were also associated solely with treatment modality in favour of PRGF, p = 0.043 and p = 0.010 respectively.

Although these preliminary results need to be evaluated in a randomized clinical trial, they provide useful infomration about the safety of PRGF and open new perspectives on autologous treatments for joint diseases.

There is a paucity of large trials investigating the effect of management strategies for paediatric non-infectious uveitis on complications requiring surgery. The purpose of our study is to investigate whether earlier initiation of systemic immunosuppression in paediatric non-infectious uveitis is associated with fewer ophthalmic surgeries. A retrospective review was conducted on 48 children with non-infectious uveitis assessed in 1998-2013. Patients were divided into uveitis diagnosed before December 2008 (group 1) and after January 2009 (group 2). Duration from uveitis onset to methotrexate initiation (U-MTX) and biological addition (U-Biologic) were reviewed. Follow-up visits with topical corticosteroids >3 times daily and active uveitis (≥1+ cells) during 3.5 years were documented. The main outcome measure was the need for ≥1 ophthalmic surgery at 3.5 years. In group 1, 69.5% of patients required ≥1 ophthalmic surgery at 3.5 years versus 26.9% in group 2 (p=0.005). U-MTX was 28.9±11.8 weeks and 14.2±10.0 weeks for groups 1 and 2 (p=0.028). U-Biologic was 134.6±46.0 weeks and 82.3±43.3 weeks for groups 1 and 2 (p=0.0016). Corticosteroid use >3 times daily was 85.9±52.7 weeks and 14.6±11.1 weeks for groups 1 and 2. Multivariate regression showed methotrexate initiation within 6 months of uveitis onset lowered the likelihood of needing ophthalmic surgery at 3.5 years (OR=6.2, 95% CI 1.2 to 33.4; p=0.033). Univariate regression demonstrated biological addition within 18 months of uveitis onset reduced the likelihood of requiring ophthalmic surgery (OR 12.57, 95% CI 1.28 to 123.48; p=0.030).

Earlier control of uveitis by addition of immunosuppressive therapy reduced the need for ophthalmic surgery.

To test for an association of periodontitis and tooth loss with rheumatoid arthritis (RA). The third National Health and Nutrition Examination Survey (NHANES III) is a nationally representative cross-sectional survey of noninstitutionalized civilians. We included participants aged > or = 60 years who had undergone both musculoskeletal and dental examinations. RA was defined based on American College of Rheumatology criteria. Dental examinations quantified decayed and filled surfaces, missing teeth, and periodontitis. Periodontitis was defined as at least 1 site exhibiting both attachment loss and a probing depth of > or = 4 mm. We classified dental health status as (1) no periodontitis, (2) periodontitis, or (3) edentulous (i.e., complete tooth loss). We performed multivariate multinomial logistic regression models with dental health status as the dependent and RA as the independent variables. The sample consisted of 4461 participants, of whom 103 were classified as having RA. Participants with RA had more missing teeth (20 vs 16 teeth; p < 0.001), but less decay (2% vs 4%; p < 0.001) than participants without RA. After adjusting for age, sex, race/ethnicity, and smoking, subjects with RA were more likely to be edentulous [odds ratio (OR) 2.27, 95% confidence interval (CI) 1.56 3.31] and have periodontitis (OR 1.82, 95% CI 1.04 3.20) compared with non-RA subjects. In participants with seropositive RA there was a stronger association with dental health status, in particular with edentulism (OR 4.5, 95% CI 1.2 17).

RA may be associated with tooth loss and periodontitis.

To compare the effect of autologous serum eye drops with different diluents in patients with dry eyes and persistent epithelial defects. Patients of Sjögren's syndrome (Group I), non-Sjögren's syndrome (group II) with dry eye, and persistent epithelial defects (Group III) were included. The eyes of each group were randomly treated with one of the following autologous serum eye drops: 100% serum (AS(100)), 50% serum with normal saline (AS(50NS)); 50% serum with sodium hyaluronate (AS(50HA)); or 50% serum with ceftazidime (AS(50CEF)). The differences in dry eye symptoms, Schirmer test I, tear break-up time (TBUT), corneal staining, and speed in epithelial healing were studied. In Group I, AS(100) showed fewer symptoms than AS(50NS), AS(50HA) and AS(50CEF) (all p < 0.01). AS(100) showed significantly better effect than AS(50NS), AS(50HA) and AS(50CEF) in decreasing corneal staining at the time point of 12-week post-treatment (p = 0.041, p < 0.001 and p < 0.001, respectively). In Group II, AS(100) was more effective than AS(50CEF) in decreasing symptoms and decreasing corneal staining (all p < 0.05). There was no significant difference in symptom and corneal staining between AS(100) and AS(50NS). In Group III, AS(100) was the most effective in achieving quick epithelial closure.

In the eyes with Sjögren syndrome and persistent epithelial defects, AS(100) was the most effective in decreasing symptoms, corneal epitheliopathy and promoting fast closure of wound. In the eyes with non-Sjögren syndrome, AS(100) and AS(50NS) have similar effects in decreasing symptoms and corneal epitheliopathy.

Patients suffering from juvenile idiopathic arthritis (JIA) frequently have affected ankle joints, which can lead to foot deformities such as pes planovalgus (JIA-PPV). Usually, JIA-PPV is diagnosed by examining the foot in non-weightbearing or in weightbearing, static condition. However, functional limitations typically appear during dynamic use in daily activities such as walking. The aim of this study was to quantify the pathophysiology of JIA-PPV in both static and dynamic condition, i.e. in upright standing and during the stance phase of walking using three-dimensional (3d) gait analysis. Eleven JIA patients (age = 12y) with at least one affected ankle joint and fixed pes planovalgus (≥5°) were compared to healthy controls (CG) (n = 14, age = 11y). Kinematic and kinetic data were obtained in barefoot standing and walking condition (1.1-1.3 m/s) with an 8-camera 3d motion analysis system including two force-plates and one pressure distribution plate. All participants were prepared using reflecting markers according to the Oxford Foot and Plug-in-Gait Model. Results were compared using the Mann-Whitney-U-test and Wilcoxon signed-rank test (p < 0.05). In comparison to CG, JIA-PPV had an excessive hindfoot/tibia eversion (p < 0.001) and a forefoot/hindfoot supination (p < 0.001) in both static and walking condition. JIA-PPV showed a greater hindfoot/tibia eversion during walking (midstance) compared to standing (p = 0.021) in contrast to CG. The arch index, measured by plantar pressure distribution, indicates a reduced arch height in JIA-PPV (p = 0.007). Patients had a lower maximum dorsiflexion of hindfoot/tibia (p = 0.001) and a lower plantarflexion of forefoot/hindfoot (p = 0.028), both when standing and walking. The kinetic results showed lower maximum ankle dorsiflexion moments (p < 0.037) as well as generated ankle power (p = 0.086) in JIA-PPV.

The pathophysiology of JIA-PPV during walking indicated that excessive hindfoot eversion produces accessory symptoms such as a reduced arch height, increased forefoot supination and reduced propulsion effect of the ankle. Muscular and coordinative insufficiency caused by arthritis can lead to the observed increased hindfoot eversion from static to dynamic condition. Conventional static or passive foot examination techniques probably underestimate deformity in JIA pes planovalgus. 3d gait analysis might be helpful in early diagnosis of this condition, especially in JIA patients with affected ankle joints.

Extra-articular manifestations of rheumatoid arthritis (RA), potentially due to systemic inflammation, include cardiovascular disease and sarcopenic obesity. Adiponectin, an adipose-derived cytokine, has been implicated in inflammatory processes in RA, but little is known regarding its association with inflammation in a pre-clinical period. Therefore, we investigated whether adiponectin was associated with inflammatory markers in individuals at risk for RA, and whether RA-related autoimmunity modifies these associations. We analyzed samples from 144 first-degree relatives (FDRs) of RA probands, of whom 23 were positive for anti-cyclic citrullinated peptide antibody and/or ≥ 2 rheumatoid factor isotypes (IgM, IgG or IgA). We called this phenotype the 'high risk autoantibody profile (HRP)' as it has been shown in prior work to be >96% specific for future RA. We measured adiponectin, cytokines, and high-sensitivity C-reactive protein (hsCRP). Using linear mixed effects models, we evaluated interaction between HRP positivity and adiponectin on inflammatory markers, adjusting for age, sex, ethnicity, body mass index, pack-years smoking, and use of cholesterol-lowering medications. In everyone, adiponectin concentration was inversely associated with hsCRP and IL-1β in adjusted models, where a 1% higher adiponectin was associated with a 26% lower hsCRP (p = 0.04) and a 26% lower IL-1β (p = 0.04). Significant interactions between HRP and adiponectin for associations with GM-CSF, IL-6, and IL-9 were detected in fully adjusted models (p = 0.0006, p = 0.006, p = 0.01, respectively). In HRP positive FDRs but not HRP negative FDRs, a 1% higher adiponectin was associated with 97% higher GM-CSF, 73% higher IL-6, and 54% higher IL-9 concentrations.

Adiponectin associates with inflammatory markers, and these associations differ in individuals with a high-risk autoantibody profile compared with those without. The interaction between adiponectin and autoimmunity warrants further investigation into the potential systemic effects of RA-related autoantibodies and adiponectin on inflammation in the absence of clinically apparent RA.

To examine the relationship between structural changes of trabecular bone and cartilage, in patients with varying degrees of osteoarthritis (OA) over 2 years, using magnetic resonance imaging. High-resolution, axial images were acquired for assessing trabecular bone structure, using a 3-D fast gradient-echo sequence. High-resolution, fat-suppressed, sagittal images were acquired for assessing cartilage structure, using a 3-D spoiled gradient-echo sequence. In a subset of the patients, sagittal images were acquired for measuring T(2) relaxation time, using a 2-D dual-echo spin echo sequence. A large variation in bone and cartilage parameters is evident among individual subjects in each group, however, group-specific means demonstrate decreasing trends (in bone and cartilage parameters) in osteoarthritic subjects (especially in mild OA subjects). The mean T(2) increased significantly (P<0.05) between the baseline and follow-up exams for all cartilage compartments except the lateral tibia. A positive relationship was established between cartilage changes and localized bone changes closest to the joint line, while a negative relationship was established between cartilage changes and global bone changes farthest from the joint line.

This study quantifies the changes in bone and cartilage structural parameters over time, and demonstrates a longitudinal relationship between the morphological changes in bone and cartilage structure in patients with varying degrees of OA. Although a large variation of bone and cartilage changes is apparent among subjects, significant trends are evident in a relatively small sample size, with a short follow-up duration.

The mouse is an optimal model organism in which gene-environment interactions can be used to study the pathogenesis of osteoarthritis (OA). The gold standard for arthritis research in mice is based on histopathology and immunohistochemistry, which are labor-intensive, prone to sampling bias and technical variability, and limited in throughput. The aim of this study was to develop a new technique that assesses mouse cartilage by integrating quantitative volumetric imaging techniques. A novel mouse model of OA was generated by cruciate ligament transection (CLT) and evaluated by histopathology and immunohistochemistry. Knee joint specimens were then imaged using a new technique that combines high-resolution micro-computed tomography (micro-CT) and phase-contrast optics followed by quantitative analyses. A comparative analysis was also performed in a previously established mouse model of OA generated by destabilization of the medial meniscus (DMM). Phase-contrast micro-CT achieved cellular resolution of chondrocytes and quantitative assessment of parameters such as articular cartilage volume and surface area. In mouse models of OA generated by either CLT or DMM, we showed that phase-contrast micro-CT distinguished control and OA cartilage by providing quantitative measures with high reproducibility and minimal variability. Features of OA at the cellular or tissue level could also be observed in images generated by phase-contrast micro-CT.

We established an imaging technology that comprehensively assessed and quantified the 2-dimensional and 3-dimensional changes of articular cartilage. Application of this technology will facilitate the rapid and high-throughput assessment of genetic and therapeutic models of OA in mice.

To study mortality from infections and accuracy of pre-mortem diagnoses in patients with rheumatoid arthritis (RA) autopsied during a 40-year period. We investigated infectious causes of death, findings at autopsy, and clinicians' estimation of cause of death in 369 consecutively autopsied RA and 371 autopsied non-RA patients with same sex, age at death, and year of autopsy. We also compiled clinical features of RA patients from medical records available and examined the association between these and infectious causes of death. Deaths from any infection were more frequent in RA (36%) than in non-RA (26%) patients. In both groups, respiratory and urinary tract infections were the most common infectious causes of death. More RA patients died from urinary tract infections than non-RA patients. In approximately half of the patients in both groups, infection as a cause of death was unrecognized before death, with no major change occurring over the 40-year study period.

Infections, especially respiratory and urinary tract infections, are frequent causes of death in RA patients. The high proportion of undiscovered infections as a cause of death highlights the diagnostic difficulty. With a decreasing number of autopsies being performed at present, greater numbers of infections may be under-reported.

To describe the hospital burden of microcrystal arthropathies in France. Data were extracted from the 2009-2011 French hospital national databases. We selected all hospital stays for microcrystal arthropathies (gout, chondrocalcinosis, other) encoded as primary or secondary diagnoses in patients older than 18. A descriptive analysis focused on number of patients and hospital stays, age, gender, comorbidities related to metabolic syndrome, and hospital costs based on 2012 public-sector costs. 132,275 hospitalizations involving 109,734 patients were related to microcrystal arthropathies encoded as primary or secondary diagnosis (61% related to gout, 34% to chondrocalcinosis, and 5% to other microcrystal arthropathies). 23,362 hospitalizations involving 25,105 patients were due to microcrystal diseases, encoded as primary diagnosis, (48% related to gout, 43% to chondrocalcinosis, and 9% to other microcrystal arthropathies). In this population, patients with chondrocalcinosis were older (mean 75.6±13.5 versus 71±16 years for other microcrystal arthropathies and 69.7±14.7 for gout). Men represented 70% of the patients with gout, 39% of those with chondrocalcinosis and 52% of the patients with other microcrystal arthropathies. Hypertension, diabetes, dyslipidemia, cardiac ischemia, and renal failure were more frequent in patients with gout than other patients. The hospital costs for microcrystal arthropathies encoded as primary diagnosis were 82.3 million Euros, 45% related to gout, 45% to chondrocalcinosis and 11% to other microcrystals.

In terms of hospital costs, gout and chondrocalcinosis represented the main part of the economic burden of crystal arthropathies and a high level of diseases belonging to the metabolic syndrome. Specific education programs favouring accurate microcrystal diagnosis and adherence to treatment could diminish this hospital economic burden.

Sulfasalazine and tetracyclines are effective against rheumatoid arthritis (RA). Levofloxacin, the bacteriologically active isomer of ofloxacin, is used in the treatment of infections caused by periodontopathic bacteria and facultative anaerobic bacteria. The aim of this study is to evaluate the clinical efficacy, safety, and tolerability of levofloxacin in patients with rheumatoid arthritis. In a 6-month, double-blind trial, we randomly assigned 76 patients with persistently active rheumatoid arthritis despite at least 6 months of methotrexate therapy at a stable dose of 15 to 25 mg per week to receive either levofloxacin (500 mg) or placebo orally once daily while continuing to receive methotrexate. The change from baseline to six months in the swollen-joint count and tender-joint count was the primary measure of efficacy. Secondary endpoints included pain, quality of life, duration of morning stiffness, erythrocyte sedimentation rate, C-reactive protein level, and physician's and patient's global assessments. The data were also analyzed to determine the number of patients meeting American College of Rheumatology criteria for 20, 50, and 70% improvement. The levofloxacin plus methotrexate was associated with the greatest reduction in the number of swollen or tender joints (P < 0.001). The levofloxacin plus methotrexate group also had significant improvement in many of the secondary outcome measures (P < 0.001). Levofloxacin was well tolerated. There were no dose-limiting toxic effects.

In patients with active rheumatoid arthritis who received methotrexate, treatment with levofloxacin significantly improved the signs and symptoms of rheumatoid arthritis.

Gout is a painful and disabling joint disease that constitutes the most common inflammatory arthritis in the US. To clarify the economic impact of gout, we systematically reviewed the literature on the direct and indirect costs associated with this disease. We conducted a literature search of MEDLINE, EMBASE, International Pharmaceutical Abstracts, NHS Economic Evaluation, and CINAHL databases to identify studies of gout and economics. We systematically reviewed published studies that met our inclusion criteria and extracted and summarized all relevant economic parameters. Reported costs were inflation-adjusted to 2013 US dollars (USD). A total of 15 studies met all eligibility criteria. Three controlled studies reported all-cause total direct costs based on specific populations (i.e., $4733, $16,925, and $18,362 per capita among employed, elderly, and treatment-refractory gout populations, respectively, and $2562, $10,590, and $7188 among corresponding non-gout patients). Two additional studies, although uncontrolled, allowed for estimation of total all-cause direct costs in unselected gout populations ($11,080 and $13,170). Gout-related costs ranged from $172 to $6179, depending on population characteristics. Six studies reported positive associations of direct costs with SUA level, gout attack frequency, or presence of tophi. Four studies reported on indirect costs, which were estimated to be as high as $4341 USD.

The available data suggest that gout patients incur substantially greater direct and indirect costs as compared with gout-free individuals among elderly and treatment-refractory gouty patients, whereas the costs are considerably less among younger, employed gouty patients. Further, direct costs increased with worsening disease characteristics.

To determine whether glutathione S-transferase GSTM1, GSTM3, GSTT1, and GSTP1 genotypes influence susceptibility or outcome in rheumatoid arthritis (RA). 277 RA patients were compared with 577 controls to examine any associations between GST genotypes and susceptibility to RA. The effect of genotypes on outcome (Larsen and functional scores) and time integrated acute phase responses (erythrocyte sedimentation rate and C reactive protein) was assessed in 122 patients with disease duration of 5-10 years. GST and HLA-DRB1 genotypes were determined using polymerase chain reaction based assays. Data were analysed using multiple regression analysis with correction for age, sex, disease duration, and the DRB1 associated shared epitope (SE) and rheumatoid factor (RF) positivity where appropriate. The GSTM1*A/*B genotype was less common in RA cases (3 of 276) than in controls (22 of 591) (exact p = 0.047), though significance was lost when adjustment was made for multiple comparisons. The Larsen score was higher (p = 0.039) in the GSTM1 null patients (89.9) than those with other GSTM1 genotypes (74.7), and this was independent of the SE. Again, correction for multiple testing resulted in loss of significance. The difference in Larsen scores between patients homozygous or negative for the SE (87.9 v 74.3) was similar to that between GSTM1 null and non-null patients. No associations between GSTM3 or GSTT1 genotypes and disease markers were identified although the association between GSTP1*B/*B and Larsen score approached significance (p = 0.096).

It is proposed that certain GSTs may influence susceptibility and radiological progression in RA and that this is independent of the effect of the HLA-DRB1 associated SE. The mechanism for this effect is presumed to be because of differences in the ability of various GST enzymes to utilise the cytotoxic products of oxidant stress. Although significance was lost after correction for multiple testing, the data indicate that further studies may be of value in RA to determine the influence of the GST and other genes involved in cellular protection against oxidative stress.

Assessment of home exercise adherence and the degree to which adherence influences changes in patient outcomes is limited by the use of self-reported measures. To determine the relationship between adherence to a home strengthening program, covertly measured by accelerometers in ankle cuff weights, and changes in self-reported pain, physical function, and knee extensor strength among people with chronic knee pain. This is a secondary analysis of data from a clinical measurement study in 54 adults, aged 45 years or older, with chronic knee pain who completed a 12-week, home-based quadriceps-strengthening program. A triaxial accelerometer was concealed in the ankle cuff weight used for exercises to assess exercise adherence. Associations between exercise adherence and changes in pain and function (measured using the Western Ontario and McMaster Universities Osteoarthritis Index) and peak isometric knee extensor strength were examined using mixed-effects and linear regression models and fractional polynomials. Exercise adherence declined from a median of 90% (interquartile range, 70%-100%) in weeks 0 to 2 to 65% (interquartile range, 25%-90%) in weeks 10 to 12. Significant improvements were observed in knee pain (mean change, -3.2 units; 95% confidence interval [CI]: -2.4, -3.9 units), function (mean change, -10.1 units; 95% CI: -7.8, -12.4 units), and knee extensor strength (mean change, 0.34 Nm/kg; 95% CI: 0.26, 0.42 Nm/kg) across the group over the same period. Exercise adherence was not associated with changes in pain, function, and knee extensor strength over 2-week periods or over the entire 12 weeks.

Covertly measured adherence to a home strengthening program was not associated with changes in patient outcomes. These findings challenge the notion that greater exercise adherence leads to greater improvement in patient outcomes during a short-term intervention.

A project aimed at developing new classification criteria for systemic lupus erythematosus (SLE) is based on weighted criteria that include both laboratory and clinical items. Combinations of certain symptoms may occur commonly in SLE, which provides an argument against independently counting these items. The current study was undertaken to evaluate the interrelationship between candidate criteria items in the International Early SLE cohort and in the Euro-Lupus cohort. The International Early SLE cohort included 389 patients, who were diagnosed within 3 years prior to the study. Data on the ACR's 1997 update of the SLE revised criteria, the Systemic Lupus International Collaborating Clinics 2012 criteria, and on 30 additional items were collected. To evaluate the interrelationship of the criteria, a tetrachoric correlation was used to assess the degree of association between different manifestations in the same organ system. The correlations identified in the International Early SLE cohort were validated in the Euro-Lupus cohort. A few relevant correlations were observed among specific clinical cutaneous manifestations (in particular, malar rash correlated with photosensitivity, alopecia, and oral ulcers) and serologic manifestations (anti-Sm and anti-double-stranded DNA and anti-RNA polymerase, anti-Ro and anti-La, and antiphospholipid antibodies), and these results were validated in the Euro-Lupus cohort. The associations within the mucocutaneous domain, hematologic and the specific autoantibodies suggest that within a single domain only the highest ranking item should be counted to avoid overrepresentation.

Some of the candidate SLE criteria cluster within domains. Given these interrelationships, multiple criteria within a domain should not be independently counted. These results are important to consider for the structure of new SLE classification criteria.

To summarize the short- and medium-term effectivenesses of stemless hip arthroplasty for treating hip joint disease in young and middle-aged patients. Between June 2005 and December 2010, 25 cases (27 hips) of hip joint disease were treated with stemless hip arthroplasty. There were 17 males (19 hips) and 8 females (8 hips) with an average age of 45.6 years (range, 30-57 years), including 13 left hips, 10 right hips, and 2 bilateral hips. The causes included avascular necrosis of the femoral head (ANFH) secondary to femoral neck fracture in 5 cases (5 hips), ANFH in 15 cases (16 hips), osteoarthritis of the hip joint caused by ankylosing spondylitis in 2 cases (3 hips), osteoarthritis of the hip joint caused by dysplasia of acetabular in 2 cases (2 hips), and rheumatoid arthritis in 1 case (1 hip). The disease duration was 1-17 years (mean, 6.1 years). Before operation, the Harris score was 47.6 ± 14.2. The incision healed by first intention in all patients, and no complications occurred, such as infection, periprosthetic fracture, and deep vein thrombosis of lower extremity. Twenty-five patients (27 hips) were followed up 36-96 months (mean, 51 months). One case (1 hip) had sciatic nerve injury after operation, which was relieved by symptomatic treatment. One case (1 hip) had prosthesis loosening, which was relieved after revision. The survival rate of prosthesis was 96.3% (26/27). At last follow-up, the Harris score was 92.1 ± 3.6, which was significantly better than preoperative score (t = 18.241, P = 0.000). The excellent and good rate was 88.9% (excellent in 19 hips, good in 5 hips, fair in 2 hips, and poor in 1 hip). The X-ray films showed good location of prosthesis, and no evidence of dislocation, bone resorption, osteolysis, and heterotopic ossification.

Because of reserving femoral neck, biomechanics conduction and distribute of the proximal femur achieve natural biomechanics state of the human body. The short- and medium-term effectivenesses of stemless hip arthroplasty for treating hip joint disease in young and middle-aged patients are satisfactory, but the long-term effectiveness need further observation.

To evaluate the thin-section computed tomographic (CT) findings of follicular bronchiolitis and compare them with the histologic findings. Thin-section CT scans obtained in 12 patients (age range, 24-77 years; mean age, 47 years) with follicular bronchiolitis proved at open lung biopsy were reviewed by two observers. Underlying conditions included rheumatoid arthritis (n = 8), mixed collagen vascular disorders (n = 2), autoimmune disorder (n = 1), and acquired immunodeficiency syndrome (n = 1). All patients had thin-section CT scans (1.0-1.5-mm collimation, 11 patients; 3.0-mm collimation, one patient; high-spatial-frequency reconstruction algorithm) obtained at 10-mm intervals through the chest. The main CT findings included bilateral centrilobular (n = 12) and peribronchial (n = 5) nodules. All 12 patients had nodules smaller than 3 mm in diameter; six patients also had nodules 3-12 mm in diameter. Areas of ground-glass opacity were present in nine (75%) patients. Histologically, all patients had lymphoid hyperplasia along the bronchioles; eight had peribronchiolar lymphocytic infiltration.

The cardinal CT feature of follicular bronchiolitis consists of small centrilobular nodules variably associated with peribronchial nodules and areas of ground-glass opacity.

The purpose of this study was to develop a method for quantitative analysis of the sonographic features of parotid glands as a noninvasive tool for the diagnosis of Sjögren's syndrome. Sonographic texture analyses were performed on the parotid glands of 44 patients with Sjögren's syndrome, 83 healthy volunteers, and 17 patients with chronic parotitis, using a fast Fourier transform program. Texture analysis of sonographic studies of the parotid gland using a Fourier transform showed that the sum of the normalized radial power spectrum in the low-spatial-frequency region (S value) of the parotid gland was significantly higher (p < .0001) in the patients with definite Sjögren's syndrome [6.70 +/- 2.13 (x10(5))] than in the 72 age-matched normal volunteers [3.25 +/- 1.08 (x10(5))]. However, patients with probable Sjögren's syndrome showed S values [3.92 +/- 1.88 (x10(5))] similar to those of the controls. On the other hand, SDs of the echo levels in the parotid gland showed significantly greater (p < .0001) values in patients with definite (4.63 1.07) and probable (4.53 1.47) Sjögren's syndrome than in the normal controls (3.30 0.76). Discriminant analysis showed that a combination of these two distinctive values increased diagnostic accuracy to 96.9%. Furthermore, S values and SDs correlated well with the qualitative grading of sonographic features and with the gradings of sialography.

The system we describe for texture analysis of sonographic images is useful in the diagnosis of Sjögren's syndrome.

The safety and effectiveness of live virus vaccines, such as the varicella-zoster vaccine, are unknown in patients with inflammatory diseases receiving immunomodulatory therapy such as tumor necrosis factor inhibitors (TNFis). To evaluate the safety and immunogenicity of the live attenuated zoster vaccine (ZVL) in patients receiving TNFis. Randomized, blinded, placebo-controlled trial. (ClinicalTrials.gov: NCT02538341). Academic and community-based rheumatology, gastroenterology, and dermatology practices. Adults aged 50 years or older receiving TNFis for any indication. Random assignment to ZVL versus placebo. Glycoprotein enzyme-linked immunosorbent assay (gpELISA) and enzyme-linked immunosorbent spot (ELISpot) from serum and peripheral blood mononuclear cells measured at baseline and 6 weeks after vaccination. Suspected varicella infection or herpes zoster was clinically assessed using digital photographs and polymerase chain reaction on vesicular fluid. Between March 2015 and December 2018, 617 participants were randomly assigned in a 1:1 ratio to receive ZVL ( Potentially limited generalizability to patients receiving other types of immunomodulators. The National Institute of Arthritis and Musculoskeletal and Skin Diseases and the American College of Rheumatology.

This trial informs safety concerns related to use of live virus vaccines in patients receiving biologics.

The postoperative treatment after a standard surgical intervention such as knee arthroplasty, proximal tibial osteotomy or supracondylar osteotomy, can have an important impact on the overall treatment outcome. In most cases, outcomes are positively effected by patients receiving physiotherapy and occupational therapy. Basic movements and range of motion need to be learnt. Self-responsible behaviour, which is similar to exercise programs in sports, needs to be supported. However, in most cases the transfer of training techniques into successful and desired postoperative care is not simple. A training technique needs to be developed which is self-explanatory, effective, encouraging for and accessible to the patient. The purpose of this study was to describe and evaluate an easy and effective technique to support regular physiotherapy in early postoperative rehabilitation using a sphygmomanometer device. Measurements were undertaken relating to handling, training results and motivation. This was a descriptive study. Forty one patients were instructed to undertake extension exercises of the knee in the early postoperative phase. A sphygmomanometer cuff was rolled out and placed just below the popliteal fossa, and inflated to 20 mmHg. In this position the patients were prompted to push the knee down with the maximum available power. The quadriceps muscle of the leg is activated when patients extend the knee using two thirds of their maximum power, and then followed by one third of their maximum power. This exercise sequence was carried out three times for 5 seconds. The results were documented by using a patient questionnaire. Thirteen patients indicated that they felt highly motivated while undertaking the training program. One patient reported poor motivation due to inconvenient handling (preparing the cuff by closing the valve screw or calculating the target value) and six patients reported that the method of handwritten recording of training sessions needed to be improved. There were no technical problems. The training results were rated as being predominantly good. Due to the variation in individual ability in extending the knee, comparison of the overall values obtained could not be done.

The use of a sphygmomanometer device is cheap and feasible technique in postoperative independent knee extension training.

The risk for disease or a bad prognosis can be calculated by means of prediction or classification models that take into account multiple variables. Different methods exist to construct such models. Some of those methods, including the likelihood ratio (LR) product method neglect dependency between variables. We aimed to evaluate the effect of neglecting dependency between variables in prediction or classification models. Population I consisted of 1003 consecutive patients with a new diagnostic problem for which RA was included in the differential diagnosis and final diagnoses (RA or non-RA) were established after 1 year. The baseline variables included in the model are rheumatoid factor, anti-citrullinated protein/peptide antibodies and the HLA-shared epitope. Population II consisted of 847 patients with definite ankylosing spondylitis (AS). Six variables (psoriasis, inflammatory bowel disease, uveitis, HLA-B27 status and latest available CRP) were evaluated. Here, specificities of the features were derived from literature and different scenarios of association between variables in controls and diseased are estimated. When two features are similarly associated in cases and controls, risks for disease will be overestimated by neglecting dependency between variables. In the presented datasets, this resulted in a up to 12% overestimation of the risk.

We showed how the height of over- or underestimation of risks can be evaluated when dependencies between two variables are neglected. This is important to evaluate the predictive value of combinations of features in cases where no data are available on associations in controls.

To estimate the prevalence of osteoarthritis (OA) of different joints in rural areas of Iran. From five villages of Tuyserkan County, 1565 individuals were randomly selected and were interviewed to complete the Community Oriented Programme for Control of the Rheumatic Diseases (COPCORD) Core Questionnaire. Among these cases 1192 cases with rheumatic complaints were examined by a rheumatologist and laboratory and radiology tests were performed if necessary for the diagnosis. Definition of OA in various joints, were based on American College of Rheumatology (ACR) criteria. About 20% of the study population had OA in at least one of their joints. Prevalence of OA in the knee joint was 19.34%, in hand joins was 2.66% and in the neck was 2.21%. The most common findings on physical examination of patients with knee OA, hand OA and neck OA were bony crepitus (88.9%), Heberden's nodes (73.2%) and pain on movement (59.9%), respectively.

This study revealed that OA in rural areas of Iran was more frequent in comparison with urban areas of Iran. Moreover, the prevalence of OA in rural areas of Iran was higher in comparison with prevalence of OA in rural areas of other Asian countries. Similar to previous studies OA was more frequently detected in the knee joint.

To assess whether the American College of Rheumatology (ACR) classification criteria for hand osteoarthritis (OA) may be used successfully to detect hand OA in population-based studies and to estimate the prevalence of hand OA in an elderly italian population. This study was part of a cross-sectional population-based survey on heart failure in the elderly (ICARe Dicomano study). All community-dwelling citizens aged >65 were considered eligible and screened by expert geriatricians for the presence of major chronic conditions, including hip, knee and hand OA, using custom-made algorithms based on standard criteria. Those subjects who screened positively were subsequently assessed by a rheumatologist. Six hundred and ninety-seven subjects (80% of the eligible population) underwent a general examination by a geriatrician. One hundred and thirty-nine of these met the ACR criteria for hand OA at screening: 22 subjects with isolated first carpometacarpal (CMC) joint OA and 117 with generalized nodal OA. 74.2% of the diagnoses were confirmed in the 101 participants re-examined in a second phase by a rheumatologist (19 subjects presented with isolated thumb-base OA and 56 with nodal OA). The estimated prevalence in the cohort was 14.9%.

The ACR clinical criteria for hand OA may be used in population studies, especially when the burden of this disease is evaluated.

In younger individuals, low absolute risk of cardiovascular disease (CVD) may conceal an increased risk age and relative risk of CVD. Calculation of risk age is proposed as an adjuvant to absolute CVD risk estimation in European guidelines. We aimed to compare the discriminative ability of available risk age models in prediction of CVD in rheumatoid arthritis (RA). Secondly, we also evaluated the performance of risk age models in subgroups based on RA disease characteristics. RA patients aged 30-70 years were included from an international consortium named A Trans-Atlantic Cardiovascular Consortium for Rheumatoid Arthritis (ATACC-RA). Prior CVD and diabetes mellitus were exclusion criteria. The discriminatory ability of specific risk age models was evaluated using c-statistics and their standard errors after calculating time until fatal or non-fatal CVD or last follow-up. A total of 1974 patients were included in the main analyses, and 144 events were observed during follow-up, the median follow-up being 5.0 years. The risk age models gave highly correlated results, demonstrating R

The cardiovascular risk age and vascular age models have comparable performance in predicting CVD in RA patients. The influence of RA disease characteristics on the predictive ability of these prediction models remains inconclusive.

Serum levels of procollagen type IIA N-terminal propeptide (sPIIANP) and type-II collagen helical peptide (sHELIXII) biomarkers were evaluated for variation diurnally and with physical activity and food in participants with osteoarthritis (OA) of the knee. Forty participants with OA of at least one knee were admitted overnight to the General Clinical Research Center for serial serum sampling. Samples were obtained on the evening (6-8 pm) of Day 1 (T3, n=40); prior to rising (8 am) from bed (T0, n=40); 1 h after rising (9 am) without food consumption (T1a, n=20); 1-2 h after rising (9-10 am) with food consumption (T1, n=40); and additionally at noon, 4 h after rising (T2, n=20). sPIIANP and sHELIXII were measured by enzyme-linked immunosorbent assay. Results were analyzed using non-parametric Freidman's test with Dunn's post-hoc multiple comparison test. Normalized mean concentrations for sPIIANP and sHELIXII increased significantly from T0 to T1 (P<0.05).

This is the first study to demonstrate diurnal variation of these collagen-II biomarkers in individuals with knee OA. These results suggest that serum sampling for these markers should be standardized for purposes of clinical trials.

This study aimed to determine whether a range of single-time-point ultrasound (US) measures of synovial disease and serologic characteristics were able to predict progression of US-defined erosive disease in patients with established rheumatoid arthritis (RA). Forty patients were studied prospectively. At baseline, subjective US measures of bone damage and synovial disease, including grayscale and power Doppler (PD) scores pre- and post-Sonovue contrast, were obtained from one proximal inter-phalangeal or metacarpo-phalangeal joint per patient. After a minimum of 2 years, the same joints were scanned to obtain a new US erosion score. Follow-up US erosion scores were obtained in 25 joints. Progressive US determined that bone damage occurred in 12/25 joints, including four of eight treated with anti-tumor necrosis factor therapy. Baseline erosion scores were significantly higher in joints that did not show progressive bone damage in the entire cohort (p = 0.05, n = 25) and a subgroup treated with disease-modifying anti-rheumatic drugs (p = 0.015, n = 17). There were no other significant differences in baseline US or serologic scores between joints that developed progressive damage and those that did not.

The majority of single-time-point US measures of synovial disease were not able to identify metacarpo-phalangeal or inter-phalangeal joint destined to develop progressive US-determined bone damage in patients with established RA. This may reflect the use of single-time-point measures, insensitivity of the US erosion score, and the long duration of RA disease in this study.

The central nervous system can regulate peripheral inflammation, but the efferent neuronal routes and the mediators remain poorly defined. One candidate is the cholinergic pathway, which releases acetylcholine (ACh). This neurotransmitter can bind to the alpha7 cholinergic receptor (alpha7R) expressed by nonneuronal cells and reduce inflammation. To test this possibility, we evaluated the expression of alpha7R and its potential role as a target in rheumatoid arthritis (RA). The expression of alpha7R in human synovium and fibroblast-like synoviocytes (FLS) was determined using immunohistochemical, Western blot, and quantitative polymerase chain reaction (PCR) analyses. The effects of ACh in vitro were determined in interleukin-1 (IL-1)-stimulated FLS using immunoassays for protein, quantitative PCR for messenger RNA (mRNA), luciferase reporter constructs for IL-6 and NF-kappaB promoter activity, and electrophoretic mobility shift assays. Expression of alpha7R was knocked down with small interfering RNA (siRNA) or was inhibited with the selective alpha7R antagonist methyllycaconitine (MLA). Protein and mRNA for alpha7R were demonstrated in RA and osteoarthritis synovium and cultured synoviocytes. Expression in synovium was mainly in the intimal lining. ACh significantly reduced the production of IL-6, CXCL8, CCL2, CCL3, CCL5, and granulocyte colony-stimulating factor by IL-1-stimulated FLS. This effect was blocked by the alpha7R antagonist MLA or by using alpha7R siRNA to knock down receptor expression. The selective alpha7R agonist PNU-282,987 decreased the production of IL-6 by IL-1-stimulated FLS. ACh did not reduce IL-6 transcription, but it decreased IL-6 mRNA half-life and reduced IL-6 mRNA steady-state levels.

The alpha7 receptor is expressed in the synovium and by synoviocytes. Receptor ligation inhibits cytokine expression in FLS through a posttranscriptional mechanism. Therefore, alpha7R is a potential therapeutic target for inflammatory diseases.

Clinical and radiologic evaluation and analyses of the surgeries using Buechel and Pappas (B-P) knee implants. The study was conducted on 60 patients who underwent 94 total knee replacement arthroplasty with B-P knee implants from May 2009 to December 2010. The results were compared to the results of 41 patients who underwent 60 knee joint surgeries using NexGen-LPS implants from January 2008 to August 2009. The American Knee Society score of the B-P knee group increased from an average of 66.9 (clinical score) and 65.5 (functional score) to 93.4 and 90.3, respectively; while those for the NexGen-LPS group increased from an average of 68.8 (clinical score) and 62.4 (functional score) to 86.3 and 76, respectively. The average ranges of motion of the B-P knee group and the NexGen-LPS group were 119.1° and 114.8°, respectively, before surgery and improved to 121.0° and 123.0° at final follow-up after the surgery. The visual analogue scale scores for the B-P knee group and the NexGen-LPS group improved from 4.7 and 4.6 to 1.4 and 1.8, respectively. The flexion contracture also improved from 5.1° and 6.3° to 0.64° and 1.72°. The tibio-femoral angle for the B-P knee group and the NexGen-LPS group also improved greatly after the surgery, from varus 0.34° and 0.73° each to valgus 6.7° and 6.9°, respectively.

The evaluation of more than 2 years of total knee replacement arthroplasty using B-P knee implants showed good results. B-P knee implants showed a relatively higher degree of satisfaction in clinical knee score and less intraoperative bone mass removal than NexGen-LPS implants.

Arthroscopy has been used to evaluate articular cartilage (AC) pathology in osteoarthritis (OA) for outcome measurement and validation of non-invasive imaging. However, many fundamental aspects of arthroscopic assessment remain un-validated. This study evaluated arthroscopic estimates of extent of chondropathy. Serial arthroscopic assessments were performed in a group of 15 sheep before and after bilateral stifle medial meniscectomy (MMx). Post-mortem assessments were performed in un-MMx sheep and 4 and 16 weeks post-MMx. Arthroscopic assessments of the extent of each grade of chondropathy were compared with a non-arthroscopic hybrid assessment that incorporated biomechanical, thickness and macroscopic assessments. Arthroscopy evaluated only 36% of AC and missed significant pathological changes, softening and chondro-osteophyte, occurring in peripheral regions. The patterns of change in arthroscopic assessments were similar to those of the non-arthroscopic assessment but there was a very strong tendency to over-estimate the extent of softened AC after MMx. In spite of these limitations arthroscopic assessments were responsive to change. Estimates of the extent of normal and softened AC were most responsive to change over time followed by estimates of superficial and deep fibrillation. Arthroscopy was as an excellent discriminator between normal and OA. Assessments of chondro-osteophyte and exposed bone were not responsive to change.

Arthroscopic estimates of extent of chondropathy are prone to substantial error. While experience and training may reduce these errors other approaches may more effectively improve performance.

Anticitrullinated peptide antibodies (ACPA) and acute phase reactants may be increased before arthritis becomes clinically detectable, suggesting that the processes underlying rheumatoid arthritis (RA) start preclinically. Whether local inflammation occurs in the preclinical phase is unknown. Therefore, we studied the small joints of ACPA positive arthralgia patients for local subclinical inflammation. Imaging was performed using 1.5 T extremity MRI. Painful hand or foot joints of 21 ACPA positive arthralgia patients without clinical arthritis were imaged. For comparison, hand and foot joints of 22 ACPA positive RA patients and 19 symptom free controls were studied. Within ACPA positive arthralgia patients, painful and symptom free joint regions were imaged. Scoring was performed according to the Outcome Measures in Rheumatology Clinical Trials (OMERACT) Rheumatoid Arthritis Magnetic Resonance Imaging Scoring (RAMRIS) method. Analyses were performed on joint region level and focused on inflammation (synovitis plus bone marrow oedema). The mean combined inflammation scores of the metacarpophalangeal/proximal interphalangeal joints of controls, painful joints of ACPA positive arthralgia patients and ACPA positive RA patients were 0.1, 0.7 and 3.7, respectively (p<0.001). Likewise, the mean combined inflammation scores of the wrist were 0.9, 2.3 and 10.3, respectively (p<0.001) and that of the metatarsophalangeal joints 0.5, 0.9 and 3.8, respectively (p=0.10). At the MCP joints, the combined inflammation score was significantly correlated with C reactive protein and erythrocyte sedimentation rate levels (rs=0.83 and rs=0.78, respectively)

The present data suggest that local subclinical inflammation occurs in ACPA positive arthralgia patients.

To evaluate the efficacy of epigallocatechin-3-gallate (EGCG), a potent antiinflammatory molecule, in regulating interleukin-1beta (IL-1beta)-induced production of the chemokines RANTES (CCL5), monocyte chemoattractant protein 1 (MCP-1/CCL2), epithelial neutrophil-activating peptide 78 (ENA-78/CXCL5), growth-regulated oncogene alpha (GROalpha/CXCL1), and matrix metalloproteinase 2 (MMP-2) activity in rheumatoid arthritis (RA) synovial fibroblasts. Fibroblasts obtained from RA synovium were grown, and conditioned medium was obtained. Cell viability was determined by MTT assay. RANTES, MCP-1, ENA-78, and GROalpha produced in culture supernatants were measured by enzyme-linked immunosorbent assay. MMP-2 activity was analyzed by gelatin zymography. Western blotting was used to study the phosphorylation of protein kinase C (PKC) isoforms and nuclear translocation of NF-kappaB. EGCG was nontoxic to RA synovial fibroblasts. Treatment with EGCG at 10 microM or 20 microM significantly inhibited IL-1beta-induced ENA-78, RANTES, and GROalpha, but not MCP-1 production in a concentration-dependent manner. EGCG at 50 microM caused a complete block of IL-1beta-induced production of RANTES, ENA-78, and GROalpha, and reduced production of MCP-1 by 48% (P < 0.05). Zymography showed that EGCG blocked constitutive, IL-1beta-induced, and chemokine-mediated MMP-2 activity. Evaluation of signaling events revealed that EGCG preferentially blocked the phosphorylation of PKCdelta and inhibited the activation and nuclear translocation of NF-kappaB in IL-1beta-treated RA synovial fibroblasts.

These results suggest that EGCG may be of potential therapeutic value in inhibiting joint destruction in RA.

To develop a method for assessing the presence and severity of radiographic features of osteoarthritis (OA) of the hip and hand, and thoracic and lumbar disc degeneration. An atlas illustrating scoring of individual radiographic features and summary grades for individual joints was developed. Three readers evaluated 31 pelvic films, 27 hand films, and 25 lateral lumbar and thoracic spine films selected from a community based sample of healthy elderly women. Interrater agreement between the 3 readers, and test-retest agreement for one of the readers, were estimated by the intraclass correlation coefficient (ICC) and kappa statistic. Interrater agreement (ICC, unless otherwise noted) for individual radiographic features of the hip ranged from 0.66 for osteophytes to 0.80 for narrowing. For the 9 interphalangeal (IP) joints of the hand, agreement ranged from 0.42 (kappa) for sclerosis to 0.93 for narrowing, and for the lumbar spine from 0.55 (kappa) for sclerosis to 0.95 for narrowing. Interrater agreement for summary grades of radiographic findings was as follows: hip, 0.81; 5 distal interphalangeal joints (DIP), 0.89; 4 proximal interphalangeal joints (PIP), 0.82; and lumbar spine, 0.93. Intrarater agreement for summary grades was as follows: hips, 0.79; 5 DIP, 0.86; 4 PIP, 0.81; and lumbar spine, 0.90.

We have developed reliable indices of the presence and severity of radiographic features of hip and hand OA and spinal disc degeneration for use in epidemiologic studies. The assessment includes grading of individual radiographic features, which allows for the independent variation in these features often found in OA and a summary grade of disease that is derived from the presence and severity of individual features.

Whether minimally invasive total knee arthroplasty (MIS-TKA) could offer better and faster recovery without the deviation of post-operative prosthesis position and limb alignment is still controversial. This prospective and randomized study was conducted to compare the clinical and radiological outcomes between patients who underwent the mini-subvastus approach of MIS-TKA and those who underwent the medial parapatellar approach of traditional TKA. Fifty patients, including 50 knees, who required TKA due to osteoarthritis were randomized to the mini-subvastus group (group I) or the medial parapatellar group (group II). All patients accepted the same method of anaesthesia, equal support therapy and identical rehabilitation exercise after surgery. The evaluation system included operation time, tourniquet time, blood loss, skin incision length in flexion, straight leg raising time, the time of lower limb muscle strength up to grade 4, the time of walking with aid or without aid, the time of walking up and down the stairs, the active flexion angle, range of movement (ROM), the Knee Society Scores (KSS), visual analogue score for pain (VAS), hospital stays and radiographic outcomes. The mini-subvastus approach offered smaller skin incision length in flexion, but at the cost of operation time (P < 0.001). No significant difference was found in tourniquet time and blood loss. The patients in group I could achieve straight leg raising, the lower limb muscle strength up to grade 4, walking with or without aid, and walking up and down the stairs earlier (P < 0.001). The active flexion angle, ROM, VAS and KSS in group I were superior to those in group II until six months post-operatively (P < 0.001), but the differences was not apparent at 12 months post-operatively. More importantly, there was no significant difference between the two groups on radiological outcomes (P > 0.05).

The mini-subvastus approach could offer faster recovery, less pain and shorter hospital stays without compromising the principles of proper prosthesis position and limb alignment compared with the medial parapatellar approach.

Activation of the inflammasome has been implicated in the pathology of various autoinflammatory and autoimmune diseases. While the NLRP3 inflammasome has been linked to arthritis progression, little is known about its synovial regulation or contribution to joint histopathology. Regulators of inflammation activation, such as interleukin (IL)-10, may have the potential to limit the inflammasome-driven arthritic disease course and associated structural damage. Hence, we used IL-10-deficient (IL-10KO) mice to assess NLRP3 inflammasome-driven arthritic pathology. Antigen-induced arthritis (AIA) was established in IL-10KO mice and wild-type controls. Using histological and radiographic approaches together with quantitative real-time PCR of synovial mRNA studies, we explored the regulation of inflammasome components. These were combined with selective blocking agents and ex vivo investigative studies in osteoclast differentiation assays. In AIA, IL-10KO mice display severe disease with increased histological and radiographic joint scores. Here, focal bone erosions were associated with increased tartrate-resistant acid phosphatase (TRAP)-positive cells and a localized expression of IL-1β. When compared to controls, IL-10KO synovium showed increased expression of Il1b, Il33 and NLRP3 inflammasome components. Synovial Nlrp3 and Casp1 expression further correlated with Acp5 (encoding TRAP), while neutralization of IL-10 receptor signaling in control mice caused increased expression of Nlrp3 and Casp1. In ex vivo osteoclast differentiation assays, addition of exogenous IL-10 or selective blockade of the NLRP3 inflammasome inhibited osteoclastogenesis.

These data provide a link between IL-10, synovial regulation of the NLRP3 inflammasome and the degree of bone erosions observed in inflammatory arthritis.

Polymyalgia rheumatica (PMR) is a common condition in the elderly. A previous study demonstrated that it is associated with an increase in bone resorption. This effect was ameliorated by steroids, implying that inflammation is the cause of increased bone resorption and that this can be reduced by steroids. This is in keeping with accumulating evidence that systemic inflammation is associated with bone resorption and bone loss. We studied bone formation and resorption markers in 53 patients with PMR prior to any therapeutic intervention. Bone resorption was measured by estimating urinary free pyridinoline (fPYD) and deoxypyridinoline (fDPD). Bone formation was estimated by measuring serum concentrations of procollagen type 1 N-terminal propeptide (P1NP). Disease activity was assessed using inflammatory markers (erythrocyte sedimentation rate and C-reactive protein). Patients had a baseline dual-energy X-ray absorptiometer scan to assess bone mineral density. Bone resorption markers were significantly increased and bone formation markers significantly decreased in PMR patients prior to treatment, compared with a control population matched for gender and age.

This implies that bone turnover is uncoupled in PMR. This may lead to a decrease in skeletal mass in the long term due to the disease process alone. However, no significant loss of bone mineral density was detected. It is possible that, due to the acute onset of PMR, increased bone resorption is not present long enough to result in a detectable decrease in bone mineral density. The effects of steroid treatment on bone metabolism and the subsequent long-term outcome need to be investigated.

Currently there is no consensus agreement on the degree of enhancement in normal temporomandibular joints (TMJ) in children, which makes it difficult for clinicians to distinguish between the presence/absence of mild synovitis. Quantitative measurements of synovial and condylar enhancement may be useful additions to current qualitative methods on early MRI diagnosis and follow up of TMJ involvement in JIA. The purpose of the study is to establish thresholds/tendencies for quantitative measures that enable distinction between mild TMJ involvement and normal TMJ appearance based on the degree of synovial and bone marrow enhancement in JIA patients. TMJ MRI examinations in 67 children with JIA and in 24 non-rheumatologic children who underwent MRI for neurologic/orbit indications were retrospectively assessed. As a priori determined TMJs of JIA patients were categorized into three groups by experienced staff radiologists based on the degree of synovial and condylar enhancement: no active disease (rheumatologic control), mild and moderate/severe findings. The signal intensity (SI) of the synovial tissue around each condyle and of the bone marrow was measured to calculate the enhancement ratio (ER) and relative SI change. The ER was calculated using signal to noise ratios, while relative SI change was calculated using signal intensities alone. Quantitative measurements of synovial and condylar enhancement of TMJs with mild or moderate/severe findings were compared with the rheumatologic and non-rheumatologic controls. Mean ER values were significantly different between the TMJs without active disease and those with mild and moderate/severe synovial enhancement, with highest values in the moderate/severe group (P < 0.0001). Similar findings were seen for condylar enhancement with P < 0.005. Relative SI change was unable to differentiate TMJs with mild synovitis from the two controls (P > 0.10). 27/60 (45%) TMJs without active disease had osteochondral changes. 8/40 (20%) TMJs in the mild group did not demonstrate any synovial thickening.

Quantitative signal to noise ratios of TMJ synovial and condylar enhancement generate thresholds/tendencies, which offer additional information to differentiate mild synovitis from normal TMJs in JIA patients. Osteochondral changes and synovial thickening may not be reliable indicators of active TMJ involvement and should be differentiated from synovial enhancement.

To explore the factors that influence risk tolerance among women from different racial/ethnic groups. In-depth individual interviews of non-Hispanic African American, non-Hispanic white, and Hispanic women ages 20-45 years were conducted by a trained interviewer using a semi-structured interview guide to elicit the factors that influence risk tolerance among minority women. The interviews were audiotaped and professionally transcribed, with a final sample size of 36 determined by thematic saturation. The members of the research team used open coding to review and develop a list of codes, which was modified as new codes emerged. A final list of 35 codes was applied to the transcripts and combined into broader themes. The study included 30.6% non-Hispanic African American, 33.3% non-Hispanic white, and 36.1% Hispanic women, with a mean ± SD age of 34.8 ± 6.8 years. Several major themes explaining risk aversion among minority women emerged: discrepancies in quality of health care, perceived prejudice, lack of knowledge and education, medication beliefs, risk perception, and constrained resources. The latter was discussed most frequently.

While our findings identify several concerns that may be addressed through implementation of more effective communication strategies by medical providers, they also highlight that disparities are strongly influenced by the complex ways financial and social constraints impact health care decisions of minority women.

To study the stability of rheumatoid factor (RF) increases and to compare the incidence of rheumatoid arthritis (RA) in people with transient or persistent increase of one or more RF isotypes. From an original cohort of nearly 14 000 participants in a population study, 135 previously RF positive persons were recruited in 1996 and evaluated according to the 1987 ACR criteria. The observation time ranged from 9-22 years (mean 16. 5). Blood samples were obtained from all participants at entry and again in 1996. About 40% of the participants who had only one raised RF isotype in the original sample had become RF negative in 1996 compared with only 15% of those with increase of two or three RF isotypes (p=0.002). The seven participants who developed RA during the study period all had persistently raised RF. Six of the 54 participants with more than one RF isotype raised in 1996 developed RA, corresponding to an annual incidence of 0.67%, which was 7.5 times higher than observed in the other participants (p=0. 045).

Symptom free persons with persistently raised RF have greatly increased risk of developing RA. This suggests that dysregulation of RF production is a predisposing factor in RA.

When performing total hip arthroplasty (THA) on a dysplastic hip, proper positioning of the acetabular component may not allow for more than 70% coverage. Structural support in the form of an autograft or a high porosity metal augment may be necessary. The purpose of the study was to investigate the value of preoperative templating and deformity classification in predicting cup coverage and the need for structural support. 65 cases of THA for DDH were retrospectively analysed. 2 observers independently classified each dysplastic hip according to Hartofilakidis and determined the extent of cup coverage via templating software on preoperative digital AP pelvic radiographs. Weighted kappa interobserver agreement was 0.68 for cup coverage and 0.76 for Hartofilakidis type. Structural support was necessary in 10 hips. No structural support was necessary in Hartofilakidis type 1, dysplasia cases. However, 27-30% of cases with type 2 or type 3 dysplasia required structural support. All cases with templated cup coverage of 65% or less required structural support. Templated coverage within 65-75% and over 75% resulted in 20% and 10% of patients receiving structural augmentation, respectively.

Preoperative planning for THA in the setting of hip dysplasia is crucial and can provide valuable insight to the need for column augmentation. However, the 3-D severity of the deformity may be underestimated in the 2-D radiographs.

The use of passaged chondrocytes is the current standard for autologous chondrocyte implantation (ACI). De-differentiation due to amplification and donor site morbidity are known drawbacks highlighting the need for alternative cell sources. Via clinically validated flow cytometry analysis, we compared the expression of human stem cell and cartilage markers (collagen type 2 (Col2), aggrecan (ACAN), CD44) of chondrocytes (CHDR), passaged chondrocytes for ACI (CellGenix™), bone marrow derived mesenchymal stem cells (BMSC), and synovial derived stem cells (SDSC). Primary, human BMSC and SDSC revealed similar adipogenic, osteogenic, and chondrogenic differentiation potential and stem cell marker expression. However, the expression of the chondrogenic markers Col2 and ACAN was statistically significant higher in SDSC. CHDR and SDSC expressed ACAN and CD44 equally, but Col2 was expressed more strongly on the SDSC surface. The marker expression of SDSC from osteoarthritic joints (Kellgren-Lawrence score ≥3) versus normal knees (Kellgren-Lawrence score ≤2) did not differ. Similarly, there was no difference between temporarily frozen and fresh SDSC. Col2 and ACAN surface expression declined with further passaging, whereas CD44 remained unchanged. We observed the same effect after reducing the serum content. When comparing CHDR for ACI with SDSC of the same passage (P2/3), both Col2 and ACAN, correlating with clinical outcome, were expressed higher in SDSC.

In summary, SDSC demonstrated high differentiation potential and a stable chondrogenic phenotype. They might therefore be better suitable for ACI than BMSC or passaged CHDR.

High mobility group box 1 protein (HMGB1) is a nuclear DNA binding protein acting as a pro-inflammatory mediator following extracellular release. HMGB1 has been increasingly recognized as a pathogenic mediator in several inflammatory diseases. Elevated serum levels of HMGB1 have been detected in autoimmune diseases including Systemic lupus erythematosus (SLE). However, the local expression of HMGB1 in active lupus nephritis (LN) is not known. Here we aimed to study both tissue expression and serum levels of HMGB1 in LN patients with active disease and after induction therapy. Thirty-five patients with active LN were included. Renal biopsies were performed at baseline and after standard induction therapy; corticosteroids combined with immunosuppressive drugs. The biopsies were evaluated according to the World Health Organization (WHO) classification and renal disease activity was estimated using the British Isles lupus assessment group (BILAG) index. Serum levels of HMGB1 were analysed by western blot. HMGB1 expression in renal tissue was assessed by immunohistochemistry at baseline and follow-up biopsies in 25 patients. Baseline biopsies showed WHO class III, IV or V and all patients had high renal disease activity (BILAG A/B). Follow-up biopsies showed WHO I to II (n = 14), III (n = 6), IV (n = 3) or V (n = 12), and 15/35 patients were regarded as renal responders (BILAG C/D).At baseline HMGB1 was significantly elevated in serum compared to healthy controls (P < 0.0001). In all patients, serum levels decreased only slightly; however, in patients with baseline WHO class IV a significant decrease was observed (P = 0.03). Immunostaining revealed a pronounced extranuclear HMGB1 expression predominantly outlining the glomerular endothelium and in the mesangium. There was no clear difference in HMGB1 expression comparing baseline and follow-up biopsies or any apparent association to histopathological classification or clinical outcome.

Renal tissue expression and serum levels of HMGB1 were increased in LN. The lack of decrease of HMGB1 in serum and tissue after immunosuppressive therapy in the current study may reflect persistent inflammatory activity. This study clearly indicates a role for HMGB1 in LN.

The aim of our descriptive study was to assess a sample of patients with knee osteoarthritis. A sample of 295 patients was assessed regarding demographical features, comorbidities, some laboratory investigations and therapeutically interventions. The predominance of females (81.4%), urban area (51.8%), age group over 50 (90.2%), primary bilateral disease (90.1%), associated with hip osteoarthritis. coxarthrosis (13.9%), essential arterial hypertension (10.9%), osteoporosis (9.5%) or obesity (8.1%) were the most frequent features of a patient admitted for knee osteoarthritis. Among therapeutically methods, patients received ultrasounds in 61.1% of cases, and kinetotherapy in 16.6%.

Our study presented news aspects regarding knee osteoarthritis, in a geographical area of north-east of Romania.

Problems of compliance with in vivo data collection and treatment protocols have been identified. This study investigated compliance with salivary cortisol sampling in a 7-day protocol. Impact of non-compliance on cortisol data was evaluated. Female fibromyalgia patients were matched with healthy female volunteers and randomized to Aware or Unaware conditions regarding objective monitoring of their sampling compliance. The protocol entailed collecting five saliva samples at prescribed times on each of 7 consecutive days. Participants self-reported time of each sample, and electronic monitor caps provided an objective date and time stamp of each sample. Objective compliance among participants unaware of monitoring was 71%, though their self-reported compliance was 93%. Aware participants' objective compliance was 90% which was consistent with self-reported compliance of 93%. Within-subject comparison of early morning rise and day slope of cortisol for compliant and non-compliant samples found significant differences with non-compliant samples resulting in flatter slopes. Patients were somewhat more compliant than healthy volunteers. Slight decrements in compliance were found for the afternoon sample (1600 h) and for the last 3 days of sampling. Compliance did not differ on weekdays versus weekends.

Self-report of compliance in a salivary cortisol sampling protocol substantially overestimates actual compliance in the absence of objective monitoring. Non-compliance with the sampling protocol results in cortisol data that significantly differs from compliant data. Awareness of electronic monitoring of sampling results in satisfactory compliance.

Follicular structures resembling germinal centres (GCs) that are characterized by follicular dendritic cell (FDC) networks have long been recognized in chronically inflamed tissues in autoimmune diseases, including the synovium of rheumatoid arthritis (RA). However, it is debated whether these ectopic structures promote autoimmunity and chronic inflammation driving the production of pathogenic autoantibodies. Anti-citrullinated protein/peptide antibodies (ACPA) are highly specific markers of RA, predict a poor prognosis, and have been suggested to be pathogenic. Therefore, the main study objectives were to determine whether ectopic lymphoid structures in RA synovium: (i) express activation-induced cytidine deaminase (AID), the enzyme required for somatic hypermutation and class-switch recombination (CSR) of Ig genes; (ii) support ongoing CSR and ACPA production; and (iii) remain functional in a RA/severe combined immunodeficiency (SCID) chimera model devoid of new immune cell influx into the synovium. Using immunohistochemistry (IHC) and quantitative Taqman real-time PCR (QT-PCR) in synovial tissue from 55 patients with RA, we demonstrated that FDC+ structures invariably expressed AID with a distribution resembling secondary lymphoid organs. Further, AID+/CD21+ follicular structures were surrounded by ACPA+/CD138+ plasma cells, as demonstrated by immune reactivity to citrullinated fibrinogen. Moreover, we identified a novel subset of synovial AID+/CD20+ B cells outside GCs resembling interfollicular large B cells. In order to gain direct functional evidence that AID+ structures support CSR and in situ manufacturing of class-switched ACPA, 34 SCID mice were transplanted with RA synovium and humanely killed at 4 wk for harvesting of transplants and sera. Persistent expression of AID and Igamma-Cmu circular transcripts (identifying ongoing IgM-IgG class-switching) was observed in synovial grafts expressing FDCs/CD21L. Furthermore, synovial mRNA levels of AID were closely associated with circulating human IgG ACPA in mouse sera. Finally, the survival and proliferation of functional B cell niches was associated with persistent overexpression of genes regulating ectopic lymphoneogenesis.

Our demonstration that FDC+ follicular units invariably express AID and are surrounded by ACPA-producing plasma cells provides strong evidence that ectopic lymphoid structures in the RA synovium are functional and support autoantibody production. This concept is further confirmed by evidence of sustained AID expression, B cell proliferation, ongoing CSR, and production of human IgG ACPA from GC+ synovial tissue transplanted into SCID mice, independently of new B cell influx from the systemic circulation. These data identify AID as a potential therapeutic target in RA and suggest that survival of functional synovial B cell niches may profoundly influence chronic inflammation, autoimmunity, and response to B cell-depleting therapies.

Despite improvements in treatment for rheumatoid arthritis (RA), psoriatic arthritis (PsA) and spondyloarthritis (axSpA), several key unmet needs remain, such as fatigue. The objective of this study was to describe the severity of fatigue, disease characteristics and socioeconomic factors in people with RA, PsA and axSpA. The study was designed as a cross-sectional survey collecting patient characteristics such as disease characteristics, socioeconomic factors and fatigue in people with RA, PsA and axSpA in Denmark. Respondents were consecutively recruited for the study over a six-month period in 2018 via routine visits to outpatient rheumatology clinics. Study nurses collected information on diagnosis, current disease-related treatment and disease activity from medical journals. People were invited to complete a questionnaire related to socioeconomic factors and containing the FACIT-Fatigue subscale. Descriptive statistics were analyzed using SAS. We invited 633 people to participate, and 488 (77%) completed the questionnaire. Women constituted 62% of respondents, and the mean age was 53.5 years. Respondents had on average been diagnosed between 11 and 15 years ago. Overall, 79% had no changes to their disease-related treatment during the past year, and the average disease activity as indicated by DAS28 for RA and PsA was 2.48 and 2.36, respectively, and BASDAI for axSpA was 28.40. Fatigue was present in all three diagnoses (mean: 34.31). The mean fatigue score varied from respondents answering that they suffered from no or little fatigue (mean: 45.48) to extreme fatigue (mean: 10.11). Analyses demonstrated that the respondents were not considerably different from nonrespondents, and the study population is considered representative compared with Danish RA and axSpA patients in the Danish National Rheumatology Registry, the DANBIO database.

We found that the majority of the study population were fatigued (61%). They had low disease activity and few disease-related treatment changes.

Osteoarthritic pain is a chronic disabling condition lacking effective treatment. Continuous use of opioid drugs during osteoarthritic pain induces tolerance and may result in dose escalation and abuse. Sigma-1 (σ1) receptors, a chaperone expressed in key areas for pain control, modulates μ-opioid receptor activity and represents a promising target to tackle these problems. The present study investigates the efficacy of the σ1 receptor antagonist E-52862 to inhibit pain sensitization, morphine tolerance, and associated electrophysiological and molecular changes in a murine model of osteoarthritic pain. Mice received an intra-knee injection of monoiodoacetate followed by 14-day treatment with E-52862, morphine, or vehicle, and mechanical sensitivity was assessed before and after the daily doses. Monoiodoacetate-injected mice developed persistent mechanical hypersensitivity, which was dose-dependently inhibited by E-52862. Mechanical thresholds assessed before the daily E-52862 dose showed gradual recovery, reaching complete restoration by the end of the treatment. When repeated treatment started 15 days after knee injury, E-52862 produced enhanced short-term analgesia, but recovery to baseline threshold was slower. Both a σ1 receptor agonist and a μ receptor antagonist blocked the analgesic effects of E-52862. An acute, sub-effective dose of E-52862 restored morphine analgesia in opioid-tolerant mice. Moreover, E-52862 abolished spinal sensitization in osteoarthritic mice and inhibited pain-related molecular changes.

These findings show dual effects of σ1 receptor antagonism alleviating both short- and long-lasting antinociception during chronic osteoarthritis pain. They identify E-52862 as a promising pharmacological agent to treat chronic pain and avoid opioid tolerance.

Rheumatoid arthritis (RA) is known to cause secondary osteoporosis and fragility fractures. This study aimed to identify biomarkers predictive of bone mineral density (BMD) change at three anatomical sites in patients with RA. We conducted a prospective longitudinal study in patients with RA. In 2012, we recruited 379 patients from an RA cohort, 329 of whom underwent evaluation of blood and urine biomarkers together with measurement of BMD in the lumbar spine, proximal femur, and distal forearm. The BMD in these three regions was reassessed in 2014. We performed multivariate linear regression analysis to identify those factors associated with BMD change. The averages of age, body mass index, and disease activity score in 28 joints (DAS28) at baseline were 63.2 (minimum to maximum, 32-85), 21.3 (12.3-30.0), and 3.2 (0.1-5.9), respectively. Univariate analysis showed that the annual BMD change was significantly associated with the use of steroid, bisphosphonate (BP) or vitamin D (VitD), and serum homocysteine in the lumber spine; DAS28, the use of BP or VitD, CRP, and anti-cyclic citrullinated peptide antibody (ACPA) in the proximal femur; and the dosage of MTX, the use of BP or VitD, and serum tartrate-resistant acid phosphatase 5b (TRACP-5b) in the distal forearm, respectively.

Predictive biomarkers for BMD change in RA patients differ at each anatomical site. Practitioners should treat each anatomical site with different markers and prescribe osteoporosis drugs to prevent fractures for RA patients.

PURPOSE OF THE STUDY AND MATERIAL: A search for sicca syndrome was performed in 54 HTLV 1 positive patients. Cases of sicca syndrome due to associated pathologies, or iatrogenic, were eliminated from this study. Lacrimal hyposecretion was found in 79% of the cases. Defective lacrimal quality was found in 86% of patients and a variable intensity coloration with the Fluorescine and/or with Rose Bengale was positive in 83% of cases. Histological study of the conjunctival print showed ocular dryness in 65% of the patients. Biopsy of the labial minor salivary glands showed a Gougerot-Sjögren syndrome in 71% of the cases.

In our study, a sicca syndrome with varied gravity was found in 78% of cases.

To investigate the performance of the Michigan Hand Outcomes Questionnaire (MHQ) in hand osteoarthritis (OA) by evaluating truth, discrimination and feasibility. Symptomatic hand OA patients from the Hand Osteoarthritis in Secondary Care (HOSTAS) cohort completed questionnaires (demographics, MHQ, Australian/Canadian Hand Osteoarthritis Index [AUSCAN], Functional Index for Hand Osteoarthritis [FIHOA] and visual analogue scale [VAS] pain) at baseline (n = 383), 1- and 2-year follow-up (n = 312, n = 293). Anchor questions at follow-up assessed whether pain/function levels were (un)acceptable and had changed compared to baseline. Correlations between MHQ and other pain/function questionnaires were calculated. Validity of unique MHQ domains (work performance, aesthetics, satisfaction), discrimination across disease stages, and responsiveness were assessed by categorizing patients by external anchors (employment, joint deformities, erosions, and anchor questions). Between-group differences were assessed with linear regression, probability plots and comparison of medians. MHQ pain and function subscales correlated moderately-to-good with other instruments (r

MHQ has several unique aspects and advantages justifying its use in hand OA, including the unique assessment of work performance, aesthetics, and satisfaction. However, MHQ, AUSCAN and FIHOA appear to measure different aspects of pain and function.

To evaluate the efficacy of treatment with acupuncture for knee osteoarthritis. We searched PUBMED, EMBASE, and the Cochrane Central Register of Controlled Trials databases from July to October 2011 for randomized controlled trials that compared needle acupuncture with sham acupuncture, standard care, or waiting list control groups in patients with knee osteoarthritis. Of the 490 potentially relevant articles, 14 RCTs involving 3,835 patients were included in the meta-analysis. Two authors independently extracted outcome data on short-term and long-term pain and functional measures. Standardized mean differences and 95% confidence intervals were calculated using the mean differences in improvements from baseline and the associated standard deviations in patients assigned to acupuncture and those assigned to control groups according to measurement time points. Compared with sham acupuncture control treatment, acupuncture was significantly better at relieving pain (p=0.002) and restoring function (p=0.01) in the short-term period, and relieving pain (p=0.06) and restoring function (p=0.06) in the long-term. Compared with the standard care and waiting list control treatments, acupuncture was significantly better at relieving pain and restoring function.

Acupuncture provided significantly better relief from knee osteoarthritis pain and a larger improvement in function than sham acupuncture, standard care treatment, or waiting for further treatment.

The incapacity of articular cartilage (AC) for self-repair after damage ultimately leads to the development of osteoarthritis. Stem cell-based therapy has been proposed for the treatment of osteoarthritis (OA) and induced pluripotent stem cells (iPSCs) are becoming a promising stem cell source. Three steps were developed to differentiate human iPSCs into chondrocytes which were transplanted into rat OA models induced by monosodium iodoacetate (MIA). After 6 days embryonic body (EB) formation and 2 weeks differentiation, the gene and protein expression of Col2A1, GAG and Sox9 has significantly increased compare to undifferentiated hiPSCs. After 15 weeks transplantation, no immune responses were observed, micro-CT showed gradual engraftment and the improvement of subchondrol plate integrity, and histological examinations demonstrated articular cartilage matrix production.

hiPSC could be an efficient and clinically translatable approach for cartilage tissue regeneration in OA cartilages.

Assessment of the use of a computerized information-tool in the context of a shared decision-making process with chronic pain patients. In the scope of a prospective and randomized study on shared decision-making with Fibromyalgia patients, a total of 75 patients had access to computer-based information about their illness. Fibromyalgia is a condition of chronic wide-spread pain, belonging to rheumatism, which mainly affects mature female patients. The majority of the patients in our study are female (93%) with an average age of 50 years. The computer-based information-tool provided the patients with detailed information about pathogenesis, typical symptoms, treatment options and prognosis. Six evaluative questions were posed to the participants concerning the assessment of the information presented, the handling of the programme, the need for an introduction to the programme, the quality of the layout and the assessment of the length of time spent in front of the computer and the assessment of the usefulness of such a tool in general practitioners' offices. Furthermore, psychological self-assessment questionnaires were filled out by the participants. The patients highly appreciate the possibility of using computer-based information-tools and endorse the implementation of such tools in general practitioners' offices. For further practical use it is crucial to provide an introduction to the handling of a computer to unskilled patients.

Computerized information leads to a better understanding of the illness and the treatment options on the part of the patient.

To outline the epidemiology and clinical pathway of acute rheumatic fever (ARF) cases in the Waikato District Health Board (DHB) region of New Zealand. An audit was carried out of the clinical notes of all recognised ARF cases from 1998 to 2004 (inclusive) residing within the Waikato DHB region at diagnosis. Cases were identified by using the hospital admissions coding system and the EpiSurv notification system. The case definition used was the New Zealand criteria for ARF diagnosis, which includes echocardiographic evidence of carditis as a major criteria. A total of 77 ARF cases were found, 8 of which were recurrences. An annual rate of 3.0 per 100,000 initial cases or 3.3 per 100,000 population (initial and recurrent cases) was documented. Over 80% of the total initial ARF cases in the Waikato DHB were in the 5-14 year age group. The overall annual incidence in this age group was 12.9 per 100,000 (age specific incidence for Maori aged 5-14 years 39.6 per 100,000 and for NZ European aged 5-14 years 2 per 100,000). The majority of cases found were Māori (83%), and residing in low socioeconomic status (80% living at the time of diagnosis within the most deprived three deciles according to NZDep01).

The presence of 77 cases in the Waikato DHB region from 1998-2004 compares unfavourably with other regions, and implies a significant burden from this disease. ARF is a preventable chronic disease with potential life-long sequelae. If the rate of ARF in Māori was reduced to that of non-Maori non-Pacific, then the burden of this disease to New Zealand communities and to the health sector would be virtually eliminated and inequalities improved.

To assess the impact of direct-to-consumer (DTC) predictive genomic risk information on perceived risk and worry in the context of routine clinical care. Patients attending a preventive medicine clinic between June 1 and December 18, 2009, were randomly assigned to receive either genomic risk information from a DTC product plus usual care (n=74) or usual care alone (n=76). At intervals of 1 week and 1 year after their clinic visit, participants completed surveys containing validated measures of risk perception and levels of worry associated with the 12 conditions assessed by the DTC product. Of 345 patients approached, 150 (43%) agreed to participate, 64 (19%) refused, and 131 (38%) did not respond. Compared with those receiving usual care, participants who received genomic risk information initially rated their risk as higher for 4 conditions (abdominal aneurysm [P=.001], Graves disease [P=.04], obesity [P=.01], and osteoarthritis [P=.04]) and lower for one (prostate cancer [P=.02]). Although differences were not significant, they also reported higher levels of worry for 7 conditions and lower levels for 5 others. At 1 year, there were no significant differences between groups.

Predictive genomic risk information modestly influences risk perception and worry. The extent and direction of this influence may depend on the condition being tested and its baseline prominence in preventive health care and may attenuate with time.

To investigate the contribution of symptoms of depression to future episodes of low back pain (LBP). A search was conducted of AMED, CINAHL, Embase, Health and Society (H&S), LILACS, MEDLINE, PsycINFO, Scopus, and Web of Science databases. We included cohort studies investigating the effect of symptoms of depression on the development of new episodes of LBP, either lifetime incidence or a recurrent episode, in a population free of LBP at baseline. We accepted the original study's definition for a new episode of LBP, and for classifying patients as LBP-free at study entry. Two independent investigators extracted data and assessed methodological quality. Meta-analyses with random effects were used to pool risk estimates. We included 19 studies, with 11 incorporated in the meta-analyses. Overall pooled results showed that symptoms of depression increased the risk of developing LBP (odds ratio [OR] 1.59, 95% confidence interval [95% CI] 1.26-2.01). The risk was similar in studies that used the diagnostic interview method (OR 1.66, 95% CI 1.14-2.42) and in studies using self-report screening questionnaires (OR 1.68, 95% CI 1.05-2.70). No statistically significant relationship was observed when we pooled studies that employed nonspecific screening questionnaires (OR 1.17, 95% CI 0.48-2.87). Three studies provided results in incremental categories of symptoms of depression and the pooled OR for the most severe level of depression (OR 2.51, 95% CI 1.58-3.99) was higher than for the lowest level (OR 1.51, 95% CI 0.89-2.56).

Individuals with symptoms of depression have an increased risk of developing an episode of LBP in the future, with the risk being higher in patients with more severe levels of depression.

To estimate the variation among rheumatologists in clinical outcomes and frequency of office visits for patients with rheumatoid arthritis (RA), after accounting for patient demographic and clinical characteristics and treatments prescribed. Multiple regression analysis using random effects for rheumatologists and adjustments for patient characteristics and treatments received, based on data derived from a panel study of persons with RA. During the years 1984-1993, rheumatologists accounted for a moderate amount of the total variation in clinical outcomes and nearly one-third of the total variation in frequency of office visits. For example, in 1993 rheumatologist associated variation in 4 clinical outcomes ranged from 16 to 25%, while the variation in office visit frequency attributable to rheumatologists stood at 46% of the total variation. However, rheumatologist associated variation in clinical outcomes was not statistically significant in any year, while variation in office visits was highly significant in all years (p < or = 0.0001). Although there was an increase in the percentage of variation attributable to rheumatologists for all outcomes examined across the years of this study, the time trend reached statistical significance only for frequency of office visits (2.4% per year; p = 0.0135) and functional status (1.6% per year; p = 0.0034).

The magnitude and strength of rheumatologist associated variation in frequency of office visits, without comparable strength in the variation in clinical outcomes, may suggest inefficiencies in the use of resources for the care of persons with RA. Further work is needed to directly examine the relationship between health outcomes and resource utilization.

To induce disease remission, early arthritis patients should adhere to their disease-modifying antirheumatic drugs (DMARD) in the first months after diagnosis. It remains unknown why some patients are non-adherent. We aimed to identify patients at risk for non-adherence in the first 3 months of treatment. Adult DMARD-naive early arthritis patients starting synthetic DMARDs filled out items on potential adherence predictors at baseline. Adherence was measured continuously. Non-adherence was defined as not opening the electronically monitored pill bottle when it should have been. Items were reduced and clustered using principal component analysis. The most discriminating items were identified with latent trait models. We used a multivariable logistic regression model to find non-adherence predictors. 301 patients agreed to participate. Adherence was high and declined over time. Principal component analysis led to 7 dimensions, while subsequent latent trait models analyses led to 15 dimensions. Two dimensions were associated with adherence, one dimension was associated with non-adherence. Rheumatologists have cues to identify non-adherence, and may intervene on non-adherence through implementing shared decision making techniques.

Information seeking behavior and positive expectations about the course of the disease are associated with adherence. Patients who become passive because of pain are at risk for non-adherence.

Immunosuppressive and anti-cytokine treatment may have a protective effect for patients with COVID-19. Understanding the immune cell states shared between COVID-19 and other inflammatory diseases with established therapies may help nominate immunomodulatory therapies. To identify cellular phenotypes that may be shared across tissues affected by disparate inflammatory diseases, we developed a meta-analysis and integration pipeline that models and removes the effects of technology, tissue of origin, and donor that confound cell-type identification. Using this approach, we integrated > 300,000 single-cell transcriptomic profiles from COVID-19-affected lungs and tissues from healthy subjects and patients with five inflammatory diseases: rheumatoid arthritis (RA), Crohn's disease (CD), ulcerative colitis (UC), systemic lupus erythematosus (SLE), and interstitial lung disease. We tested the association of shared immune states with severe/inflamed status compared to healthy control using mixed-effects modeling. To define environmental factors within these tissues that shape shared macrophage phenotypes, we stimulated human blood-derived macrophages with defined combinations of inflammatory factors, emphasizing in particular antiviral interferons IFN-beta (IFN-β) and IFN-gamma (IFN-γ), and pro-inflammatory cytokines such as TNF. We built an immune cell reference consisting of > 300,000 single-cell profiles from 125 healthy or disease-affected donors from COVID-19 and five inflammatory diseases. We observed a CXCL10+ CCL2+ inflammatory macrophage state that is shared and strikingly abundant in severe COVID-19 bronchoalveolar lavage samples, inflamed RA synovium, inflamed CD ileum, and UC colon. These cells exhibited a distinct arrangement of pro-inflammatory and interferon response genes, including elevated levels of CXCL10, CXCL9, CCL2, CCL3, GBP1, STAT1, and IL1B. Further, we found this macrophage phenotype is induced upon co-stimulation by IFN-γ and TNF-α.

Our integrative analysis identified immune cell states shared across inflamed tissues affected by inflammatory diseases and COVID-19. Our study supports a key role for IFN-γ together with TNF-α in driving an abundant inflammatory macrophage phenotype in severe COVID-19-affected lungs, as well as inflamed RA synovium, CD ileum, and UC colon, which may be targeted by existing immunomodulatory therapies.

To evaluate the sensitivity and specificity of criteria designed for spondyloarthritis in a university hospital treated population of children with late onset pauciarticular juvenile chronic arthritis and a control population. Four sets of criteria especially designed for juvenile patients: Garmisch-Partenkirchen juvenile spondylitis criteria (= Garmisch), SEA (=seronegative enthesopathy and arthritis) syndrome, Enthesitis Related Arthritis (ERA), Atypical spondyloarthritis for children and two sets of criteria for patients without age specification (European spondyloarthropathy Study Group - ESSG and Amor) were evaluated in a cross-sectional way in a group of 43 consecutive patients with late onset pauciarticular juvenile chronic arthritis (LOPA) seen over a six-month period in the outpatient clinic. These criteria were analysed in 69 patients with other forms of juvenile chronic arthritis as well. The sensitivity and specificity were calculated for each set, as well as positive predictive value and likelihood ratio. The characteristics described in the different sets of criteria were separately evaluated in the LOPA patients and the other patients. For sensitivity, the Garmisch criteria scored the highest value (97.7%). However, sensitivity was significantly lower in two of the juvenile sets (SEA syndrome and Atypical spondyloarthritis), respectively 44.2% and 51.2%, as opposed to the other criteria (>85%; p<0.01 by Mc Nemar test). Specificity and positive predictive value (PPV) was the highest for the SEA syndrome criteria (98.5%, vs. 95.0%) followed by the ERA (95.6 % vs. 92.1 %) and the Garmisch criteria (94.2% vs. 91.3%). The positive likelihood ratio (LR+) was >10 in SEA (30.5), ERA (18.7) and Garmisch (16.8). The negative likelihood ratio (LR-) was <0.1 only in the Garmisch criteria (0.02).

Sensitivity, specificity, PPV, LR+ and LR- for the Garmisch-Partenkirchen criteria suggest that they classify almost the same population as defined by LOPA. The SEA syndrome criteria, which were not designed to be classification criteria, being very specific, cannot be used in this patient population to classify a sufficient number of patients. The sensitivity and specificity for the ESSG criteria being similar in these children as in adults suggest they have similar characteristics. The Garmisch-Partenkirchen criteria and/or LOPA definition are major candidates for future research in identifying spondyloarthritis in juvenile patients.

Alarmins S100A8 and S100A9 are major products of activated macrophages regulating cartilage damage and synovial activation during murine and human osteoarthritis (OA). In the current study, we investigated whether S100A8 and S100A9 are involved in osteophyte formation during experimental OA and whether S100A8/A9 predicts osteophyte progression in early human OA. OA was elicited in S100A9-/- mice in two experimental models that differ in degree of synovial activation. Osteophyte size, S100A8, S100A9 and VDIPEN neoepitope was measured histologically. Chondrogenesis was induced in murine mesenchymal stem cells in the presence of S100A8. Levels of S100A8/A9 were determined in plasma of early symptomatic OA participants of the Cohort Hip and Cohort Knee (CHECK) cohort study and osteophytes measured after 2 and 5 years. Osteophyte size was drastically reduced in S100A9-/- mice in ligaments and at medial femur and tibia on days 21 and 42 of collagenase-induced OA, in which synovial activation is high. In contrast, osteophyte size was not reduced in S100A9-/- mice during destabilised medial meniscus OA, in which synovial activation is scant. S100A8 increased expression and activation of matrix metalloproteinases during micromass chondrogenesis, thereby possibly increasing cartilage matrix remodelling allowing for larger osteophytes. Interestingly, early symptomatic OA participants of the CHECK study with osteophyte progression after 2 and 5 years had elevated S100A8/A9 plasma levels at baseline, while C-reactive protein, erythrocyte sedimentation rate and cartilage oligomeric matrix protein were not elevated at baseline.

S100A8/A9 aggravate osteophyte formation in experimental OA with high synovial activation and may be used to predict osteophyte progression in early symptomatic human OA.

Evidence suggests that foot problems are common in juvenile idiopathic arthritis (JIA), with prevalence estimates over 90%. The aim of this survey was to describe foot-related impairment and disability associated with JIA and foot-care provision in patients managed under modern treatment paradigms, including disease-modifying anti-rheumatic drugs (DMARDs) and biologic therapies. The Juvenile Arthritis Foot Disability Index (JAFI), Child Health Assessment Questionnaire (CHAQ), and pain visual analogue scale (VAS) were recorded in 30 consecutive established JIA patients attending routine outpatient clinics. Foot deformity score, active/limited joint counts, walking speed, double-support time (s) (DS) and step length symmetry index % (SI) were also measured. Foot-care provision in the preceding 12 months was determined from medical records. Sixty-three per cent of children reported some foot impairment, with a median (range) JAFI subscale score of 1 (0-3); 53% reported foot-related activity limitation, with a JAFI subscale score of 1 (0-4); and 60% reported participation restriction, with a JAFI subscale score of 1 (0-3). Other reported variables were CHAQ 0.38 (0-2), VAS pain 22 (0-79), foot deformity 6 (0-20), active joints 0 (0-7), limited joints 0 (0-31), walking speed 1.09 m/s (0.84-1.38 m/s), DS 0.22 s (0.08-0.26 s) and SI +/-4.0% (+/-0.2-+/-31.0%). A total of 23/30 medical records were reviewed and 15/23 children had received DMARDS, 8/23 biologic agents and 20/23 multiple intra-articular corticosteroid injections. Ten children received specialist podiatry care comprising footwear advice, orthotic therapy and silicone digital splints together with intrinsic muscle strengthening exercises.

Despite frequent use of DMARD/biologic therapy and specialist podiatry-led foot care, foot-related impairment and disability persists in some children with JIA.

The treatment target for patients with rheumatoid arthritis (RA) is remission. Imaging techniques and remission criteria may identify patients at risk of flare and associated consequences. This study aimed to determine the clinical, functional and imaging associations of disease flare in patients with RA in remission and any effect on long-term outcomes. RA patients in clinical remission as determined by their treating rheumatologist were assessed using clinical, remission criteria, imaging, functional and quality of life measures over 12 months. Flare was defined as any increase in disease activity requiring a change in therapy. 26% of patients (24/93) in remission experienced a flare within 1 year. Fulfilment of remission criteria was not associated with a reduced likelihood of flare. Increased baseline ultrasound power Doppler (PD) activity (unadjusted OR (95% CI) 4.08 (1.26 to 13.19), p=0.014) and functional disability (Health Assessment Questionnaire Disability Index (HAQ-DI) per 0.1 unit1.27 (1.07 to 1.52), p=0.006) were independently associated with risk of flare. Patients who had a flare had significantly worse long-term clinical (Disease Activity Score 28; mean (95% CI) 2.90 (2.55 to 3.24) vs 2.26 (2.06 to 2.46), p=0.002) and functional outcomes (HAQ-DI; 0.412 (0.344 to 0.481) vs 0.322 (0.282 to 0.362), p=0.029) at 12 months compared with patients in sustained remission.

The presence of PD activity was the most accurate determinant of flare in RA patients in remission. Flare was associated with worse clinical and functional outcomes. These results suggest ultrasound could form an important part of remission assessment in RA.

To determine the cost-effectiveness of treatment sequences of biologic disease-modifying anti-rheumatic drugs or Janus kinase/STAT pathway inhibitors (collectively referred to as bDMARDs) vs conventional DMARDs (cDMARDs) from the US societal perspective for treatment of patients with moderately to severely active rheumatoid arthritis (RA) with inadequate responses to cDMARDs. An individual patient simulation model was developed that assesses the impact of treatments on disease based on clinical trial data and real-world evidence. Treatment strategies included sequences starting with etanercept, adalimumab, certolizumab, or abatacept. Each of these treatment strategies was compared with cDMARDs. Incremental cost, incremental quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) were calculated for each treatment sequence relative to cDMARDs. The cost-effectiveness of each strategy was determined using a US willingness-to-pay (WTP) threshold of $150,000/QALY. For the base-case scenario, bDMARD treatment sequences were associated with greater treatment benefit (i.e. more QALYs), lower lost productivity costs, and greater treatment-related costs than cDMARDs. The expected ICERs for bDMARD sequences ranged from ∼$126,000 to $140,000 per QALY gained, which is below the US-specific WTP. Alternative scenarios examining the effects of homogeneous patients, dose increases, increased costs of hospitalization for severely physically impaired patients, and a lower baseline Health Assessment Questionnaire (HAQ) Disability Index score resulted in similar ICERs.

bDMARD treatment sequences are cost-effective from a US societal perspective.

To evaluate radiographically the humeroulnar (HU) and humeroradial (HR) joint spaces in patients with long-term rheumatoid arthritis (RA). An inception cohort of 74 patients with RA were followed for 15 yr. At the end-point, 148 elbows were radiographed by a standard method. The HU and HR joint spaces were examined from the anteroposterior radiographs by measuring the shortest tangential distance in the middle of the joints. Destruction of the elbow joints, assessed with the Larsen method on a scale of 0-5, was studied in relation to the joint-space measurements. Mean (s.d.) HU joint space (n=148) in RA patients was 2.5 (1.1) mm, range 0-4 mm [2.9 (0.8) mm in men and 2.4 (1.1) mm in women]. Mean (s.d.) HR joint space (n=140) was 2.3 (0.9) mm, range 0-4 mm [2.5 (0.8) mm in men and 2.3 (1.0) mm in women]. HU and HR spaces of the affected joints (Larsen grades 2-5) [1.9 (s.d. 1.1) and 1.8 (0.9) mm respectively] were notably narrower than those of the unaffected (Larsen grades 0-1) joints [3.1 (0.7) and 2.9 (0.6) mm]. All the joints graded as Larsen 4 or 5 (n=13) had a value of 0 mm for both joint spaces. Both the HU and the HR joint-space narrowing was associated with increasing destruction (Larsen grading) of the joint. [r= -0.69 (95% CI -0.77 to -0.60) and r= -0.70 (-0.78 to -0.60)]. The monotonic narrowing was significantly increasing from unaffected (Larsen 0, 1), slightly (2), moderately (3) to severely (4, 5) affected joints (P<0.001). A step in this process occurred between Larsen grades 3 and 4, when the mean joint space diminished from 1.4 and 1.5 respectively to 0 mm.

Joint-space narrowing is a frequent consequence of rheumatoid affection of the elbow joint. HR joint space decreases together with HU joint space; however, the HR joint space is already slightly narrower at the start. The narrowing is a rather late phenomenon, occurring only after erosive destruction. This should be borne in mind when using the Larsen method to evaluate changes in the elbow joint.

Cartilage degradation in osteoarthritis (OA) generates the type II collagen fragments, Helix-II and CTX-II that can be used as clinical biological markers. Helix-II and C-telopeptide of type II collagen (CTX-II) levels are associated independently with progression of OA suggesting that they may be generated through different collagenolytic pathways. In this study we analyzed the release of Helix-II and CTX-II from human cartilage collagen by the proteinases reported to play a role in cartilage degradation. In vitro, human articular cartilage extract was incubated with activated human recombinant cathepsins (Cats) and matrix-metalloproteases (MMPs). Next, we analyzed the spontaneous release of Helix-II and CTX-II from cartilage sections of patients with knee OA who were immediately deep frozen after joint replacement to preserve endogenous enzyme activity until assay. Cartilage sections were then incubated for up to 84 h in the presence or absence of E-64 and GM6001, inhibitors of cysteine proteases and MMPs, respectively. In vitro, Cats K, L and S generated large amount of Helix-II, but not CTX-II. Cat B generated CTX-II fragment, but destroyed Helix-II immunoreactivity. Cat D was unable to digest intact cartilage. MMPs-1, -3, -7, -9, and -13 efficiently released CTX-II, but only small amount of Helix-II. Neither CTX-II nor Helix-II alone was able to reflect accurately the collagenolytic activity of Cats and MMPs as reflected by the release of hydroxyproline. In OA cartilage explants, E-64 blunted the release of Helix-II whereas the release of CTX-II could be completely abrogated by GM6001 and only partly by E-64.

These in vitro and ex vivo experiments of human cartilage suggest that Helix-II and CTX-II could be released in part by different enzymatic pathways. Helix-II and CTX-II alone reflect only partially overall cartilage collagen degradation. These findings may explain why these two biological markers could provide complementary information on disease progression in OA.

Regular physical activity is safe and beneficial for people with rheumatoid arthritis (RA) but the majority of people with RA are less active than the general population and have a higher risk of co-morbidities. Exploring strategies used by physically active people with RA could inform effective methods to support those who are less active. To explore the perspectives, experiences and strategies employed by people with RA who successfully engage with regular physical activity. Individual semi-structured interviews and thematic analysis. A purposive sample of physically active people with RA. Twelve females and three males participated (mean age 56, range 29 to 80; mean disease duration 13 years, range 10 months to 46 years). Analysis revealed eight constructs clustered into three themes. Theme 1: 'the individual' incorporated constructs of symptoms, feelings and role; theme 2: 'management' incorporated medical and self-management; theme 3: 'physical activity' incorporated constructs of type of physical activity, including barriers or facilitators. Participants reported a long history of physical activity prior to diagnosis and good support networks. All participants recognised that physical activity was key to their RA management, acknowledged the benefits from engaging in physical activity and were able to overcome barriers. Participants had strong beliefs that physical function would decline without regular physical activity.

People with RA who successfully maintain physical activity are motivated by a desire to manage symptoms, resist functional decline and maintain health and independence. These findings should be explored with a wider range of people with RA.

Cell types present in synovial joint tissues and during synovitis are known to produce epidermal growth factor receptor (EGFR)/ErbB-1/HER-1 and the potent EGFR-ligand transforming growth factor-alpha (TGF-alpha) in vitro. Concomitant expression of TGF-alpha, EGFR, and ErbB2 gives a strong proliferative drive in vitro and in vivo. However, the presence of TGF-alpha and members of the EGFR/EGFR-ligand family has not been thoroughly investigated in joint tissue in vivo. We aimed to determine whether TGF-alpha, EGFR, and ErbB2 are present in human synovial joints, especially during rheumatoid arthritis (RA). TGF-alpha protein was immunodetected in knee synovial fluid (SF) collected from 23 RA patients, eight patients with other arthritic conditions, two osteoarthritis (OA) patients, and six post-traumatic patients (control). TGF-alpha mRNA and TGF-alpha, ErbB2, EGFR, and CD68 immunoreactivity were detected in knee synovial biopsies (6 RA/2 OA/6 control) using in situ hybridization and immunohistochemistry. TGF-alpha mRNA was determined in SF cells by reverse transcription polymerase chain reaction (RT-PCR) and/or the Northern blot technique. TGF-alpha protein was found in the synovial membrane (SM) and in the majority of SF samples. TGF-alpha levels were significantly higher (p < 0.001) in SF of RA patients than controls, TGF-alpha protein and mRNA were increased and more widespread in SM of RA patients. In addition, white blood cells collected from RA SF expressed TGF-alpha mRNA. Immunoreactivity for ErbB2 was found in SM and was more widespread in RA patients than in controls.

The presence of TGF-alpha in normal SF and SM may indicate a physiological maintenance function. The increased expression of TGF-alpha and ErbB2 in RA SF and SM may give rise to an abnormal growth pattern, contributing to inflammatory synovial hyperplasia.

Integral to an orthopaedic surgeon-patient informed consent discussion is the assessment of patient comprehension of their medical care. However, little is known about how to optimize patient comprehension of an informed consent discussion. The purpose of our study was to evaluate three time-controlled informed consent discussion methods to determine which optimized patient comprehension immediately after the discussion. Sixty-seven consecutive patients with knee osteoarthritis who were considered medically appropriate for a knee corticosteroid injection were enrolled in our trial. Participants were randomized and were allocated into one of three groups in a parallel fashion and 1:1:1 ratio. Our three groups varied by sensory input and included verbal (hearing), verbal and video (hearing and sight), and verbal and model (hearing, sight, and touch). Each participant listened to a 10-minute scripted lecture given by a researcher; this lecture was based on content from the American Academy of Orthopaedic Surgeons patient education web site OrthoInfo. Patient comprehension was assessed after the lecture using a validated questionnaire called the Nkem test. Our primary outcome evaluated patient comprehension utilizing a pairwise comparison of mean comprehension scores between the groups. The primary outcome was analyzed using a one-way analysis of variance with the least significant difference calculated post hoc and a 95% confidence interval (95% CI). The health-care staff, study participants, and outcome assessor were each blinded to group assignments. The mean comprehension scores were 84% (95% CI, 79% to 88%) for the verbal and model group, 74% (95% CI, 63% to 80%) for the verbal and video group, and 71% (95% CI, 61% to 80%) for the verbal group. The omnibus analysis of variance was significant and showed a difference among the groups (p = 0.019). The pairwise comparison of the groups using the least significant difference calculated post hoc showed that the verbal and model group outperformed the verbal group (p = 0.01) and the verbal and video group (p = 0.023).

Multisensory patient education incorporating OrthoInfo and an anatomic model optimized patient comprehension immediately after a time-controlled informed consent discussion. This finding could play an important role in improving surgeon-patient communication in the field of orthopaedic surgery.

This study compared human primary osteoblasts derived from hip osteoarthritis (OA) cases against controls (CTLs) to investigate candidate OA disease genes, twist homologue 1 (TWIST1), wingless MMTV integration site family member 5B (WNT5B), transforming growth factor-β (TGFβ1) and SMAD family member 3 (SMAD3), during osteoblast differentiation, relative to calcium apposition and elemental mineral composition. Primary osteoblast cultures were generated from intertrochanteric trabecular bone samples from five female primary hip OA cases and five age-matched female CTLs. During a 42-day differentiation time-course, alizarin red stains, energy-dispersive X-ray spectroscopy and real-time RT-polymerase chain reaction (PCR) were used to quantify calcium, elemental composition and gene expression, respectively. Data were analysed using linear mixed effects models and Pearson correlation matrices. Significant differences, correlations and associations were found in OA and CTL osteoblasts between gene and mineral measures. The calcium: phosphorous (Ca:P) ratio was significantly more varied in OA compared to CTL. Calcium apposition, mineral composition as well as TWIST1 and TGFβ1 mRNA expression changed significantly over time. TWIST1 mRNA expression was elevated and correlated with SMAD3 mRNA levels in the OA cohort during the time-course. Associations were observed between tissue non-specific alkaline phosphatase (TNAP), osteocalcin (OCN), TWIST1, TGFβ1, SMAD3 mRNA levels and mineral measures in OA against CTL. Temporal differences between SMAD3 mRNA expression and mineral composition were also found in OA.

Dysregulated expression of TWIST1, TGFβ1 and SMAD3 mRNA observed in OA bone is reflected in the functionality of the osteoblast when these cells are cultured ex vivo. The results presented here are consistent with at least part of the aetiology of primary hip OA deriving from altered intrinsic properties of the osteoblast.

The complement system is crucial for the development of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). In particular, C5a plays a central role. In this study, plasma and urinary levels of C5a as well as renal C5a receptors (CD88 and C5L2) expression were investigated in patients with AAV. Twenty-four patients with AAV in the active phase, 19 patients with AAV in the remission phase, and 20 patients with lupus nephritis (LN) were included. Plasma and urinary levels of C5a were measured with enzyme-linked immunosorbent assay (ELISA). The staining of CD88 and C5L2 in renal specimens was detected with immunohistochemistry. The level of plasma C5a was significantly higher in patients with AAV in the active phase than that in patients in remission, that in patients with LN, and that in normal controls. The urinary C5a level was significantly higher in patients with AAV in the active phase than that in patients in remission and that in normal controls, but not significantly different between patients with active AAV and patients with LN. The mean optical density of CD88 staining in the tubulointerstitium was significantly lower in AAV patients than that in normal controls (0.0052 ± 0.0011 versus 0.029 ± 0.0042; P = 0.005). The mean optical density of C5L2 in glomeruli was significantly higher in AAV patients than that in normal controls (0.013 ± 0.0027 versus 0.0032 ± 0.0006; P < 0.001). The mean optical density of CD88 staining closely correlated with the initial eGFR (r = 0.835; P < 0.001) in AAV patients. Double-labeling immunofluorescence assay suggested that CD88 did not express on neutrophils, monocytes, or macrophages, but C5L2 expressed on neutrophils (or monocytes) and macrophages.

The elevated plasma and urinary C5a levels indicated complement activation in human AAV. The level of renal CD88 expression could reflect the disease severity of ANCA-associated glomerulonephritis. CD88 expression was downregulated, and C5L2 was upregulated in ANCA-associated glomerulonephritis.

Total hip replacement (THR) involves the replacement of a damaged hip joint with an artificial hip prosthesis. Resurfacing arthroplasty (RS) involves replacement of the joint surface of the femoral head with a metal surface covering. To undertake clinical effectiveness and cost-effectiveness analysis of different types of THR and RS for the treatment of pain and disability in people with end-stage arthritis of the hip, in particular to compare the clinical effectiveness and cost-effectiveness of (1) different types of primary THR and RS for people in whom both procedures are suitable and (2) different types of primary THR for people who are not suitable for hip RS. Electronic databases including MEDLINE, EMBASE, The Cochrane Library, Current Controlled Trials and UK Clinical Research Network (UKCRN) Portfolio Database were searched in December 2012, with searches limited to publications from 2008 and sample sizes of ≥ 100 participants. Reference lists and websites of manufacturers and professional organisations were also screened. Systematic reviews of the literature were undertaken to appraise the clinical effectiveness and cost-effectiveness of different types of THR and RS for people with end-stage arthritis of the hip. Included randomised controlled trials (RCTs) and systematic reviews were data extracted and risk of bias and methodological quality were independently assessed by two reviewers using the Cochrane Collaboration risk of bias tool and the Assessment of Multiple Systematic Reviews (AMSTAR) tool. A Markov multistate model was developed for the economic evaluation of the technologies. Sensitivity analyses stratified by sex and controlled for age were carried out to assess the robustness of the results. A total of 2469 records were screened of which 37 were included, representing 16 RCTs and eight systematic reviews. The mean post-THR Harris Hip Score measured at different follow-up times (from 6 months to 10 years) did not differ between THR groups, including between cross-linked polyethylene and traditional polyethylene cup liners (pooled mean difference 2.29, 95% confidence interval -0.88 to 5.45). Five systematic reviews reported evidence on different types of THR (cemented vs. cementless cup fixation and implant articulation materials) but these reviews were inconclusive. Eleven cost-effectiveness studies were included; four provided relevant cost and utility data for the model. Thirty registry studies were included, with no studies reporting better implant survival for RS than for all types of THR. For all analyses, mean costs for RS were higher than those for THR and mean quality-adjusted life-years (QALYs) were lower. The incremental cost-effectiveness ratio for RS was dominated by THR, that is, THR was cheaper and more effective than RS (for a lifetime horizon in the base-case analysis, the incremental cost of RS was £11,284 and the incremental QALYs were -0.0879). For all age and sex groups RS remained clearly dominated by THR. Cost-effectiveness acceptability curves showed that, for all patients, THR was almost 100% cost-effective at any willingness-to-pay level. There were age and sex differences in the populations with different types of THR and variations in revision rates (from 1.6% to 3.5% at 9 years). For the base-case analysis, for all age and sex groups and a lifetime horizon, mean costs for category E (cemented components with a polyethylene-on-ceramic articulation) were slightly lower and mean QALYs for category E were slightly higher than those for all other THR categories in both deterministic and probabilistic analyses. Hence, category E dominated the other four categories. Sensitivity analysis using an age- and sex-adjusted log-normal model demonstrated that, over a lifetime horizon and at a willingness-to-pay threshold of £20,000 per QALY, categories A and E were equally likely (50%) to be cost-effective. A large proportion of the included studies were inconclusive because of poor reporting, missing data, inconsistent results and/or great uncertainty in the treatment effect estimates. This warrants cautious interpretation of the findings. The evidence on complications was scarce, which may be because of the absence or rarity of these events or because of under-reporting. The poor reporting meant that it was not possible to explore contextual factors that might have influenced study results and also reduced the applicability of the findings to routine clinical practice in the UK. The scope of the review was limited to evidence published in English in 2008 or later, which could be interpreted as a weakness; however, systematic reviews would provide summary evidence for studies published before 2008. This study is registered as PROSPERO CRD42013003924. The National Institute for Health Research Health Technology Assessment programme.

Compared with THR, revision rates for RS were higher, mean costs for RS were higher and mean QALYs gained were lower; RS was dominated by THR. Similar results were obtained in the deterministic and probabilistic analyses and for all age and sex groups THR was almost 100% cost-effective at any willingness-to-pay level. Revision rates for all types of THR were low. Category A THR (cemented components with a polyethylene-on-metal articulation) was more cost-effective for older age groups. However, across all age-sex groups combined, the mean cost for category E THR (cemented components with a polyethylene-on-ceramic articulation) was slightly lower and the mean QALYs gained were slightly higher. Category E therefore dominated the other four categories. Certain types of THR appeared to confer some benefit, including larger femoral head sizes, use of a cemented cup, use of a cross-linked polyethylene cup liner and a ceramic-on-ceramic as opposed to a metal-on-polyethylene articulation. Further RCTs with long-term follow-up are needed.

The purpose of this study was to evaluate the joint gap kinematics in posterior-stabilized total knee arthroplasty (PS TKA). Between January 2010 and April 2011, 44 consecutive patients (55 knees) who underwent primary PS TKA using the navigation system were assessed. There were 37 women and 7 men with a mean age at operation of 63 years (range; 58-73 years). After fixation of all components with cement and insertion of polyethylene trial insert, medial and lateral joint gap measurements were carried out without distraction force and separately using a navigation system on each flexion angles. The joint gaps were measured before and after deflation of tourniquet, first with patella everted and then reduced. Deflation of tourniquet did not effect on gap. In patellofemoral joint reduction situation, the medial gap relatively maintained throughout the range of knee motion, but the lateral gap is gradually decreasing with knee flexion from 30° to 120° flexion. However, in patellar eversion situation, the medial gap showed a significant increase and also statistically significantly increased compared with patellar reduced position over 90° knee flexion status, but the lateral gaps are decreased compared with patellofemoral reduction situation throughout the range of knee motion except full flexion status. In more physiologic status that is patella reduced and tourniquet deflated status, the average medial joint gap change was 2.30 ± 1.64 mm and the average lateral joint gap change was 2.90 ± 1.53 mm throughout the range of motion.

Medial and lateral joint gaps showed different patterns with patellar eversion and patellofemoral joint reduction. However, such changes occurred within 3 mm in average throughout whole range of knee motion even with multi-radius femoral component.

The etiology of knee osteoarthritis (OA), the most common form of arthritis, is complex and may differ by race or ethnicity. In recent years, genetic studies have identified many genetic variants associated with OA, but nearly all the studies were conducted in European whites and Asian Americans. Few studies have focused on the genetics of knee OA in African Americans. We performed a genome-wide association study of radiographic knee OA in 1217 African Americans from 2 North American cohort studies: 590 subjects from the Johnston County Osteoarthritis Project and 627 subjects from the Osteoarthritis Initiative. Analyses were conducted in each cohort separately and combined in an inverse variance fixed effects metaanalysis, which were then included in pathway analyses. We additionally tested 12 single-nucleotide polymorphisms robustly associated with OA in European white populations for association in African Americans. We identified a genome-wide significant variant in

These results highlight differences in the genetic architecture of knee OA between African American and European whites. This finding underscores the need to include more diverse populations in OA genetics studies.

Pain and disability are the main clinical manifestations of osteoarthritis, for which only symptomatic therapies are available. Hence, there is a need for therapies that can simultaneously alter disease progression and provide pain relief. KBP is a dual amylin- and calcitonin-receptor agonist with antiresorptive and chondroprotective properties. In this study we investigated the effect of KBP in a rat model of osteoarthritis. Medial meniscectomy (MNX) was performed in 39 rats, while 10 underwent sham surgery. Rats were treated with KBP and/or naproxen. Nociception was assessed by mechanical and cold allodynia, weight bearing asymmetry, and burrowing behavior. Blood samples were collected for biomarker measurements, and knees for histology. Cartilage histopathology was evaluated according to the advanced Osteoarthritis Research International (OARSI) score and KBPs in vitro antiresorptive effects were assessed using human osteoclasts cultured on bone. The MNX animals displayed an increased nociceptive behavior. Treatment with KBP attenuated the MNX-induced osteoarthritis-associated joint pain. The cartilage histopathology was significantly lower in rats treated with KBP than in MNX animals. Bone and cartilage degradation, assessed by CTX-I and CTX-II plasma levels, were decreased in all KBP-treated groups and KBP potently inhibited bone resorption in vitro.

Our study demonstrates the effectiveness of KBP in ameliorating osteoarthritis-associated joint pain and in protecting the articular cartilage, suggesting KBP as a potential drug candidate for osteoarthritis.

The literature supporting the role of a specific drug in the onset of drug-induced antineutrophil cytoplasmic antibody-associated vasculitis (AAV) mainly relies on case reports or short series and implicates old treatments. The advent of new treatments may have modified the epidemiology of these adverse drug reactions. This study was undertaken to update the list of drugs associated with AAV by using a pharmacovigilance-based data mining approach. We collected data on adverse drug reactions reported using the Medical Dictionary for Regulatory Activities preferred term "anti-neutrophil cytoplasmic antibody positive vasculitis" up to November 2020 from the World Health Organization pharmacovigilance database (VigiBase). For each retrieved drug, a case-noncase analysis was performed, and disproportionate reporting was calculated by using the information component (IC). A positive IC A total of 483 deduplicated individual case safety reports of drug-induced AAV involving 15 drugs with an IC

Our findings strengthen the evidence of an association of AAV with previously suspected drugs, but also identify 3 new drugs that may cause drug-induced AAV. Particular attention should be given to these drugs by prescribers and in experimental studies.