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Physical activity is essential for ensuring optimal physical function and fitness in children with juvenile idiopathic arthritis (JIA). Although exercise intervention trials informed current clinical practice, few studies addressed why children with JIA do or do not participate in exercise interventions. We aimed to describe perceived barriers and facilitators to the uptake and adherence to a 6-month home-based exercise intervention for children diagnosed with JIA and their parents. A convenience sample of children (n = 17) and their parents (n = 17) were recruited from a group of 23 child-parent dyads participating in an exercise intervention study; the Linking Exercise, Activity and Pathophysiology Exercise Intervention (LEAP-EI) study. Child-parent dyads completed in-depth semi-structured one-to-one interviews with a trained interview moderator prior to starting the exercise program and 11 dyads completed follow-up interviews at the end of the 6-month program. We also conducted 'exit' interviews with one child-parent dyad, one child and one parent following three participants' withdrawal from the exercise intervention. Interviews were transcribed and transcripts were analyzed using a five-step framework analysis to categorize data into themes. Thematic analysis of pre-exercise program interview transcripts revealed three reasons child-parent dyads initiated the exercise program: 1) potential health benefits, 2) selflessness and 3) parental support. Analysis of post-exercise intervention transcripts identified four main themes within a priori themes of barriers and facilitators to program adherence (median of 46.9%; 5.4, 66.7 IQR): 1) parental support, 2) enjoyment, 3) time pressures (subthemes: time requirement of exercise, scheduling, forgetting) and 4) physical ailments.

Major barriers to and facilitators to exercise for children with JIA fell into three categories: personal, social and programmatic factors. These barriers were not unlike those that emerged in previous exercise intervention trials with healthy children and youth. There is a need to develop effective strategies to engage children in physical activity and to overcome barriers that prevent them from doing so. Future initiatives may potentially engage children in developing solutions to enhance their participation in and commitment to physical activity.

To examine the use of nonpharmacologic treatment by patients with osteoarthritis (OA) and rheumatoid arthritis (RA). Patients were recruited from physicians' offices in Ontario, Canada. All participants completed questionnaires that asked about their health status, use of medications and nonpharmacologic treatments, and use of health care resources. A total of 326 patients with OA and 253 patients with RA completed the survey on the use of nonpharmacologic treatment. Only 73% of patients with OA had been told to use nonpharmacologic modalities, but 98.8% had tried at least 1 type of treatment. About 97% of those with RA had been told to use and had tried at least 1 type of treatment. Most patients continued to use a treatment once they had tried it.

The use of nonpharmacologic modalities is common among patients with arthritis. It is important that clinicians address with their patients the appropriate use of and barriers to continuing these treatments.

We evaluated whether patient-reported outcome trajectories (i.e., changes over time) differed by intraoperative compartmental cartilage lesion pattern over 4-6 years following arthroscopic meniscal surgery. In this ancillary study of the Knee Arthroscopy Cohort Southern Denmark cohort, we intraoperatively categorized cartilage lesions as isolated patellofemoral, isolated tibiofemoral, or combined patellofemoral/tibiofemoral. Participants completed the Knee injury and Osteoarthritis Outcome Score (KOOS) pre-operatively, at 3 and 12 months, and at 4-6 years post-operatively and reported overall satisfaction at final follow-up. Our main outcome was KOOS Of 630 participants with complete cartilage scores, 280 (44%) were women, mean (standard deviation) age was 49 (13) years, and BMI was 27.3 (4.4) kg/m

Though KOOS

Osteoarthritis (OA) is the most common cause of musculoskeletal pain and disability. The knee is the most common site of OA. Numerous studies have shown an inconsistency between patients' reports of pain and their radiographic findings. This inconsistency may be partially explained by the fact that a portion of the pain originates from the myofascial trigger points (MTrPs) located in the surrounding muscles. To assess the role of myofascial pain in OA patients. Critical review. PubMed, Google Scholar, Scopus, and PEDro databases were searched from inception until December 2016 for the following keywords: "myofascial pain", "osteoarthritis", "trigger points", "knee" or any combination of these words. The reference lists of all articles retrieved were searched as well. The current review included two observational studies evaluating the prevalence of MTrPs in OA patients and six interventional studies describing the treatment of myofascial pain in OA patients. Data from two of the interventional studies also included an observational section.

The reviewed observational studies offered initial evidence as to the assumption that myofascial pain and the presence of MTrPs may play a role in pain and disability of knee OA. Because of the cross-sectional design of these studies, the causal relationships could not be established. Additional studies are needed to confirm this assumption as well as to clarify if MTrPs are a portion of OA etiology or that OA is the basis for MTrPs formation. Each interventional study elaborated on various myofascial treatment techniques. However, treatment focusing on MTrPs seems to be effective in reducing pain and improving function in OA patients. Due to the heterogeneity in treatment methods and outcome measures, it is difficult to attain a definite conclusion and therefore, additional high-quality randomized controlled trials are warranted.

Bone strength depends on multiple factors such as bone density, architecture and composition turnover. However, the role these factors play in osteoporotic fractures is not well understood. The aim of this study was to analyze trabecular bone architecture, and its crystal and organic composition in humans, by comparing samples taken from patients who had a hip fracture (HF) and individuals with hip osteoarthritis (HOA). The study included 31 HF patients and 42 cases of HOA who underwent joint replacement surgery between 1/1/2013 and 31/12/2013. Trabecular bone samples were collected from the femoral heads and analyzed using a dual-energy X-ray absorptiometry, micro-CT, and solid-state high-resolution magic-angle-spinning nuclear magnetic resonance (MAS-NMR) spectroscopy. No differences in proton or phosphorus concentration were found between the two groups using

Patients with HO who did not sustain previous hip fractures had a higher femoral head BMD, BV/TV, and Tb.N than HF patients. In HO patients, BMD was positively correlated with the BV/TV and Tb.N and negatively correlated with the femoral head organic content and trabecular separation. Interestingly, these correlations were not found in HF patients with relatively lower bone densities. Therefore, osteoporotic patients with similar low bone densities could have significant microstructural differences. No differences were found between the two groups at a HA crystal level.

The aim of the study was to study pre- and postoperative symptoms, radiological findings and operative complications in rheumatoid arthritis (RA) patients, operated in the atlantoaxial joint. A retrospective study of 31 RA patients (24 women, seven men) operated for anterior atlantoaxial subluxation (aAAS) at the Neurosurgical Department, Aarhus University Hospital, in the period of 1993-2003. Information was obtained retrospectively from the patients charge. Mean age at RA debut was 38 years (16-69 yrs), and neck symptoms were seen after a mean time of 15 years (0-39 yrs) of illness. Radiological examination at this time showed irreversible atlantoaxial changes, and operation was performed within 0-9 years (mean 1.6 yrs). The patients were characterized by high disease activity: C-reactive protein, anaemia, positive IgM-rheumatoid factor (84%), and progressive radiological changes in the peripheral joints. All patients were treated with DMARDs (disease modifying anti rheumatic drugs). Neck pain (100%) and neurological symptoms/manifestations (87%) were seen preoperatively. After operation symptoms were relieved in 68% of the patients, while 22% were unchanged, and 10% had worsened. Postoperative complications included cardiac death, dislocation of the cervical spine, fracture of arcus atlantis, hemiparesis, dysphagia, bed sores and infection of the surgical scar (29%).

Neck symptoms were seen after 15 years of illness, and within the following 1.6 years patients were operated for aAAS. After the operation most of the patients (68%) had relief from symptoms, while 29% had postoperative complications, including cardiac death, dislocation of the cervical spine, fracture of arcus atlantis, hemiparesis, dysphagia, bed sores and infection in the surgical scar.

Osteoarthritis (OA) and cardiovascular disease (CVD) share age and obesity as risk factors, but may also be linked by pathogenic mechanisms involving metabolic abnormalities and systemic inflammation. This study compared the prevalence of OA and metabolic syndrome (MetS) in subjects with OA versus the general population without OA to determine whether having OA predicts increased cardiovascular risk. National Health and Nutrition Examination Survey III data were used as a representative sample of the general US population. Subjects included adults aged > or = 18 years with records of history, physical, radiographic, and laboratory data adequate to assess for diagnoses of MetS and OA. Logistic regression was used to examine the association between MetS and population-weighted variables. The general population sample included 7714 subjects (weighted value representing 174.9 million population), of whom 975 subjects had OA (weighted value 17.5 million) and 6739 did not (weighted value 157.4 million). Metabolic syndrome was prevalent in 59% of the OA population and 23% of the population without OA. Each of the 5 cardiovascular risk factors that comprise MetS was more prevalent in the OA population versus the population without OA: hypertension (75% vs 38%), abdominal obesity (63% vs 38%), hyperglycemia (30% vs 13%), elevated triglycerides (47% vs 32%), and low high-density lipoprotein cholesterol (44% vs 38%). Metabolic syndrome was more prevalent in subjects with OA regardless of sex or race. The association between OA and MetS was greater in younger subjects and diminished with increasing age. Having OA at age 43.8 years (mean age of the general population) was associated with a 5.26-fold (SE = 1.58, P < 0.001) increased risk of MetS. This association remained strong when obesity was controlled for in additional regression models.

Osteoarthritis is associated with an increased prevalence of MetS, particularly in younger individuals. Global cardiovascular risk should be assessed in individuals aged < or = 65 years with OA, and should be considered when prescribing analgesics for OA patients.

To determine the clinical effects of juvenile pubic symphysiodesis (JPS) treatment in hip dysplasia-prone puppies with comparison to similar untreated control puppies. Controlled clinical case study. Thirty-nine dysplastic puppies, of which six were part of the control group, with a positive Ortolani or hip distraction index (DI)≥0.40. The following eight clinical tests were evaluated preoperatively, and at one and two years postoperatively: Ortolani, hip reduction angle (HRA), gait evaluation, osteoarthritis, hip pain, and three Norberg angles (angle-extended mode [N-OFA], angle-compression mode [N-COM], and angle-distracted mode [N-DIS]). Juvenile pubic fusion (JPS) was performed by unipolar electro-cautery at 12 to 24 weeks of age; the control puppies received a sham operation. For the JPS puppies, the mean osteoarthritis level did not significantly increase (11%). There was a 74% reversal of preoperative positive Ortolani signs. Hip reduction angle, DI and N-DIS also improved significantly. Only N-DIS fully detected Norberg angle laxity. Within the control group, osteoarthritis increased significantly (55%) with no improvement in Ortolani incidence, N-OFA or N-COM angles. A decrease in HRA and DI was associated with increased osteoarthritis levels. Signs of hip pain increased by 33%, which was not significant. Dogs with initial severe hip laxity (DI≥0.70) experienced progressive osteoarthritis.

In JPS dogs with preoperative mild to moderate hip laxity (DI = 0.40-0.69), insignificant osteoarthritis occurred at two years. Juvenile pubic symphysiodesis surgery also improved other clinical criteria (Ortolani, HRA, hip pain, N-DIS). Osteoarthritis was generally not prevented by JPS in dogs with initial severely lax hips (DI≥0.70). Juvenile pubic symphysiodesis surgery at 12 to 24 weeks of age was an effective and safe pre-emptive bilateral treatment for mild to moderate hip dysplasia.

To examine changes in the extent of specific patterns of interstitial lung disease (ILD) as they transition from one pattern to another in response to immunosuppressive therapy in systemic sclerosis-related ILD (SSc-ILD). We evaluated changes in the quantitative extent of specific lung patterns of ILD using volumetric high-resolution computed tomography (HRCT) scans obtained at baseline and after 2 years of therapy in patients treated with either cyclophosphamide (CYC) for 1 year or mycophenolate mofetil (MMF) for 2 years in Scleroderma Lung Study II. ILD patterns included lung fibrosis, ground glass, honeycombing, and normal lung. Net change was calculated as the difference in the probability of change from one ILD pattern to another. Wilcoxon's signed rank test was used to compare the changes. Forty-seven and 50 patients had baseline and follow-up scans in the CYC and MMF groups, respectively. Mean net improvements reflecting favorable changes from one ILD pattern to another in the whole lung in the CYC and MMF groups, respectively, were as follows: from lung fibrosis to a normal lung pattern, 21% and 19%; from a ground-glass pattern to a normal lung pattern, 30% and 28%; and from lung fibrosis to a ground-glass pattern, 5% and 0.5%. The mean overall improvement in transitioning from a ground-glass pattern or lung fibrosis to a normal lung pattern was significant for both treatments (all P < 0.001).

Significantly favorable transitions from both ground-glass and lung fibrosis ILD patterns to a normal lung pattern were observed in patients undergoing immunosuppressive treatment for SSc-ILD, suggesting the usefulness of examining these transitions for insights into the underlying pathobiology of treatment response.

To provide a survey of disease activity in patients treated with standard care in Italian clinical practice. This was an observational prospective cohort study in patients with early, aggressive rheumatoid arthritis (RA; duration ≤2 years but ≥6 weeks; DAS28 >3.2) naïve to anti-tumour necrosis factor (TNF) therapy who were treated with disease-modifying anti-rheumatic drugs (DMARDs) and/or biologics according to standard practice at 15 Italian ARPA (Artrite Reumatoide Precoce Aggressiva) centres. Patients were evaluated at baseline and after 6, 12 and 24 months. The primary endpoint was the proportion of patients achieving remission, as defined by disease activity score in 28 joints (DAS28) <2.6, after 1 year. Among the 152 patients enrolled, 92 were evaluable after 1 year and 77 after 2 years for DAS28. At baseline, patients had a mean DAS28 of 6.1±1.0. At 12 months, 62.6% of patients were treated with DMARDs (in monotherapy or in combination), and 37.4% with anti-TNFs (in monotherapy or in association with DMARDs). At 24 months, 35.1% were receiving anti-TNF therapy. The rate of DAS28 remission rates at 12 months and 24 months were 28.3% (95% confidence interval [CI] 19.1-37.5) and 41.6% (95% confidence interval [CI] 30.6-52.6), respectively.

The remission rate was lower at 12 months compared with previous large randomised clinical trials for early, aggressive RA, but significantly improved at 24 months. These results suggest that patients in real-world clinical settings in Italy may experience a delay in receiving the best possible care.

The aim of this study was to compare serum and synovial fluid levels of matrix metalloproteinase-13 (MMP-13) and tumor necrosis factor-alpha (TNF-α) in 2 stages of osteoarthritis, and investigate their correlation with Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores. Forty-two patients (mean age: 64±8.8 years) with grade 3 and grade 4 knee osteoarthritis according to Kellgren-Lawrence criteria were enrolled in the study and underwent total knee arthroplasty. TNF-α and MMP-13 levels were measured preoperatively from venous blood samples and intraoperatively from knee synovial fluid via enzyme-linked immunosorbent assay. Preoperative and 1-month postoperative knee functions were assessed by WOMAC. Grade 4 synovial fluid MMP-13 (4.76±5.82 pg/ml) was elevated compared to grade 3 (3.95±4.45), whereas grade 3 serum MMP-13 (1.128±0.308 pg/ml) was found elevated compared to grade 4 (1.038±0.204) (p=0.438, p=0.430, respectively). Grade 4 serum TNF-α (0.253±0.277) was elevated compared to grade 3 (0.206±0.219), whereas grade 3 synovial fluid TNF-α (0.129±0.052) was elevated compared to grade 4 (0.118±0.014). Positive correlation was observed between synovial fluid MMP-13 levels and postoperative WOMAC scores. Mean serum TNF-α (0.226±0.246 pg/ml) was elevated compared to synovial levels (0.124±1.59), and synovial MMP-13 (4.31±1.24) was elevated compared to serum levels (1.089±1.519).

Despite the systemic increase in TNF-α levels concordant with osteoarthritis grade, MMP-13 levels are elevated via local manner, with a significant correlation with WOMAC scores.

Unicompartmental osteoarthrosis increasingly affects younger patients who have high expectations concerning their postoperative level of activity. However, there is no available data on the activity level after fixed-bearing lateral unicompartmentalkneearthroplasty (UKA). The aim of this study was to report sports activity after fixed-bearing lateral UKA with a minimum two-year follow up. Nineteen patients were surveyed to determine their sporting activities at a mean follow up of 4.6 years (range 2.0-9.7 years) after fixed-bearing lateral UKA. We also assessed the Knee Injury and Osteoarthritis Outcome Score Joint Replacement (KOOS JR) Score and the University of California, Los Angeles activity scale (UCLA scale) at baseline and latest follow up. Before the onset of the first symptoms, 15 of 19 patients were active in at least one sport compared with 13 of 19 patients after surgery. Eighty-six per cent of the patients returned to activity. Within 6 months, 68% returned to their activities after surgery. The mean postoperative UCLA score was 6.4 (±1.3). Half of the patients reached a high activity level (UCLA ≥ 7). Most common activities after surgery were long walks, biking and hiking. High-impact activities showed a significant decrease.

Eighty-six per cent of the patients were able to return to regular recreational and sporting activities. In general, a shift from high-impact to low-impact activities was observed. There was no difference in the number of disciplines performed. Overall, the session length and frequency remained unchanged. However, male patients and younger patients participated in sports less frequently compared with preoperative levels.

This study examined adherence, discontinuation, and switching of rheumatoid arthritis (RA) biologics over a 1-year period after initiation of the biologic treatment in Medicaid patients with RA. The study sample consisted of Medicaid patients with RA in California, Florida and New York who had newly initiated etanercept (n=1359), anakinra (n=267), or infliximab (n=1012) between January 1, 2000 and December 31, 2002. Adherence (proportion of days covered (PDC)≥0.80), discontinuation (90-day continuous gap), and switching (initiation of second biologic within 90days of discontinuation date of index biologic) were measured during the 12-month postindex biologic initiation. Sensitivity analyses were conducted by varying the thresholds to define these measures. Logistic regressions examined the factors associated with RA biologic adherence and discontinuation. Anakinra users had the lowest mean PDC (0.36) and percent adherent patients (11%) followed by etanercept users (mean PDC: 0.57; % adherent: 32%) and infliximab users (mean PDC: 0.64; % adherent: 43%). All three groups had high discontinuation rates (41% etanercept, 76% anakinra, and 41% infliximab). Few patients who discontinued the index biologic switched to another biologic. Logistic regressions found that patients in Florida had lower odds of being adherent and higher odds of discontinuing their index biologic than patients in California. Anakinra users had lower odds and infliximab users had higher odds of being adherent than etanercept users. Anakinra users had higher odds of discontinuation than etanercept users.

This study highlights the poor adherence to and premature discontinuation without concurrent switching of RA biologics that should raise concern for clinicians as well as payers.

To determine the effects of the disease modifying antirheumatic drug (DMARD) leflunomide on the expression of the matrix metalloproteinase MMP-1 (collagenase) and the activity of MMP-9 that are believed to play a major role in cartilage destruction associated with inflammation in patients with rheumatoid arthritis (RA). Serum concentrations of cartilage oligomeric matrix protein (COMP) should offer promise for monitoring tissue degradation in the RA joints during a 6-month therapy with leflunomide. Thirty-six patients with RA meeting the ACR-criteria were recruited for the study in a multicentre trial. A dose of 20 mg leflunomide/day (after a 3-day 100 mg/day loading dose), an isoxazole derivate and inhibitor of the "de novo" pyrimidine synthesis, was administered for a study period of 6 months. MMP-1, the activity of MMP-9 and COMP values were measured in serum by enzyme immuno assay. The very sensitive acute phase protein serum amyloid A (SAA) was also determined by EIA. The measurements were performed before and after 3 and 6 months of leflunomide therapy. High levels of active MMP-9, COMP and SAA were detected in the sera of the patients with RA prior to the start of the leflunomide therapy compared to normal control sera. A significant reduction of the MMP-9 activity levels was seen after 3 months immunomodulation with leflunomide and was maintained after 6 months (p < 0.01). The degradation marker COMP and the inflammation marker SAA decreased significantly after 6 months (p < 0.04, respectively p < 0.01). There was also an insignificant tendency of MMP-1 reduction in serum after 6 months.

This study demonstrated that a DMARD therapy with leflunomide can cause positive effects on cartilage degradation and inflammation achieving reductions in the acute phase protein SAA, the enzymatic attack of MMPs and the loss of the cartilage matrix component COMP.

While systemic lupus erythematosus and lupus nephritis (LN) disproportionately affect females, previous studies suggest that males may experience poorer outcomes. We undertook this study to investigate sex differences in health care utilization, end-stage renal disease (ESRD), and mortality among patients with LN receiving Medicaid, public insurance for low-income individuals. Within the Medicaid Analytic eXtract (MAX) from 29 states (from 2000 to 2010), we used billing claims to identify individuals ages 5-65 years with incident LN (positive predictive value 80%). MAX data were linked to the US Renal Data System to determine ESRD and to Social Security Death Index files to determine death. We estimated adjusted incidence rate ratios (IRRs) by sex for health care utilization using Poisson regression, and we used multivariable proportional hazards models to compare risks of ESRD and death by sex. Of 2,750 patients with incident LN, 283 (10%) were male. The mean ± SD follow-up period for both sexes was 3.1 ± 2.3 years. The mean ± SD age was 29.6 ± 13.9 years among females and 24.7 ± 14.1 years among males (P < 0.01). Males had fewer outpatient visits (IRR 0.88 [95% confidence interval (95% CI) 0.80-0.97]) and fewer emergency department visits (IRR 0.75 [95% CI 0.63-0.90]). The 5-year cumulative incidence of ESRD was 22.3% in males and 21.2% in females. The 5-year cumulative incidence of death was 9.4% in males and 9.8% in females. Comparing males to females, there were no sex differences in ESRD (subdistribution hazard ratio [HR] 1.05 [95% CI 0.76-1.45]) or death (HR 0.81 [95% CI 0.47-1.35]).

In this cohort of patients with incident LN, ESRD and mortality were extremely high overall but were not increased among males compared to females. In this vulnerable population, biologic and health care utilization differences by sex may not significantly affect outcomes.

To compare the responsiveness of 2 disease-specific questionnaires, the Modified Health Assessment Questionnaire (MHAQ) and the Arthritis Impact Measurement Scale (AIMS2) with corresponding dimensions (physical function, mental health, pain, and fatigue) in a generic health status measure [the MOS Short Form-36)] in patients with rheumatoid arthritis (RA). Within the framework of an observational study, a prospective cohort of 595 patients with RA from a community based patient register responded to a questionnaire at baseline and after 2 years' followup. Changes in patient global disease activity assessed on a categorical verbal rating scale (range 1-5) were used as external indicator of improvement or deterioration. Responsiveness was evaluated with standardized response means (SRM), calculated as mean change score divided by the standard deviation of the mean change score. Changes in patient global disease activity were classified as much better (n = 33), slightly better (n = 108), no change (n = 291), slightly worse (n = 108), and much worse (n = 20). There were no significant differences in responsiveness between SF-36 and the disease-specific measures within the same dimensions of health. The SRM of the tools within the dimension of pain (AIMS2 and SF-36) were moderate (0.5-0.8) to large (> 0.8) consistently in both directions (improvement and deterioration). The physical function subscales detected the same pattern, but the magnitude of the gradients was smaller. The fatigue and mental health subscales did not show any clear and consistent pattern of change.

In patients with RA, there was no difference in responsiveness of subscales from SF-36 and disease-specific instruments when using changes in patient assessed global disease activity as an external indicator of change in health status. The dimension of pain was most sensitive to changes in patient assessed global disease activity followed by physical function, fatigue, and mental health.

Previous research has demonstrated that testosterone therapy causes a profound suppression of autoimmune disease in lacrimal glands of female mouse models of Sjögren's syndrome. The aim of the present study was to determine whether other anabolic androgens, nonandrogenic steroids, or immunosuppressive agents might duplicate this hormonal effect. For comparative purposes, we also evaluated the influence of these various pharmacologic compounds on the tear volume, the magnitude of lymphocyte infiltration in the submandibular gland, and the extent of mucosal and peripheral lymphadenopathy. Female MRL/MpJ-lpr/lpr mice were administered vehicle, steroids, or immunosuppressive compounds for 21 days after the onset of disease. Lacrimal glands and tears, as well as submandibular glands, spleens, and superior cervical and mesenteric lymph nodes were collected immediately before or after treatment and then processed for analysis. Our results showed that: (1) the immunosuppressive impact of testosterone on lymphocyte infiltration in lacrimal tissue was reproduced by the administration of 19-nortestosterone or cyclophosphamide, but not by therapy with 17 beta-estradiol, danazol, the experimental steroid Org 4094, cyclosporine A or dexamethasone; (2) treatment with testosterone, 19-nortestosterone, cyclophosphamide, or dexamethasone significantly reduced the extent of inflammation in salivary glands; (3) exposure to cyclophosphamide markedly diminished the size of lymphatic and splenic tissues, whereas glucocorticoid treatment only decreased the weight of superior cervical lymph nodes; and (4) administration of 17 beta-estradiol, Org 4094, or dexamethasone led to a significant decrease in tear volume.

Overall, these results demonstrate that androgen or cyclophosphamide therapy may successfully ameliorate autoimmune expression in lacrimal and salivary glands of a female mouse model of Sjögren's syndrome.

Recent guidelines recommend measurement of articular loss over several years, determined by conventional X-rays, as the principal outcome measure in clinical trials of potential structure-modifying drugs in osteoarthritis (OA). The aim of this study was to assess the impact of the joint space width measurement method on sample size calculation in knee OA studies. Standard knee X-rays were taken in 212 patients with knee OA at baseline and after 3 years of follow-up. Mean joint space width (JSW) was measured with an in-house computer-assisted method. Minimum JSW, measured with a graduated magnifying lens, was taken as external standard. After calculation of the intra- and inter-observer reproducibility of the JSW, sensitivity to change was assessed using the standardized response mean (SRM). The number of patients needed to identify a mean significant difference of 0.5 mm in joint space narrowing between the placebo and the treated group, after 3 years of follow-up, was then calculated. JSW measured with the computer-assisted technique showed better intra- and inter-observer reproducibility than when using the magnifying lens. JSW values measured with our computer-assisted method were significantly correlated with JSW values obtained using the magnifying lens (r=0.87, p<0.001). The SRM were 0.44 and 0.40 for the computer-assisted method and magnifying lens, respectively. The number of patients needed was 131 per group using the computer-assisted method, and 104 using the magnifying lens.

Our method of measurement of JSW may be of potential use in longitudinal studies evaluating the effect of structure-modifying drugs in OA, due to its high level of precision and efficiency. However, although sensitivity to change is markedly better with the digitized method compared with the graduated magnifying lens, we recommend the measurement of mean and minimum JSW in structure-modifying OA trials.

To describe the health-related quality of life (HRQOL) of persons with and without arthritis in the 50 US states and the District of Columbia, and to determine correlates of poor HRQOL in persons with arthritis. Data from the Behavioral Risk Factor Surveillance System were used. Descriptive analyses were age standardized and multivariate analyses used logistic regression. Of persons ages ≥18 years with arthritis, 27% reported fair/poor health, compared to 12% without arthritis. The mean numbers of physically unhealthy, mentally unhealthy, and activity-limited days for persons with arthritis exceeded those for persons without arthritis. In regression analyses, black non-Hispanics reported better HRQOL than white non-Hispanics, especially in the ≥14 versus 0 days comparisons. Yet no difference existed in self-reported health status between these two groups. Having a low family income and being unable to work were both strongly associated with poor HRQOL. Being physically active was associated with better HRQOL. Binge drinking was associated with poor HRQOL for some measures, but was associated with better self-reported health. Cost being a barrier to care and having diabetes mellitus were strongly associated with worse HRQOL.

Adults from the US with arthritis had worse HRQOL than those without. Physical health and mental health were both affected by arthritis; therefore, efforts to alleviate the arthritis burden should address both domains. Given the current and projected high prevalence of arthritis, we face a significant burden of poor HRQOL. Increasing physical activity, reducing comorbidities, and increasing access to health care could improve the HRQOL of persons with arthritis.

The aim of this study was to assess the relationship between the two types of posttranslational modifications of proteins in RA: glycosylation on the example of carbohydrate-deficient transferrin and citrullination by means of autoantibodies to cyclic citrullinated peptides. The study was carried out in 50 RA patients. CDT was measured using N Latex CDT immunonephelometric test, the results were presented in absolute and relative units. Anti-CCP were measured using the chemiluminescent method and rheumatoid factor by immunoturbidimetric method. 80% of RA patients were positive for anti-CCP, 70% for RF and 62% for both, anti-CCP and RF. The level of %CDT was significantly elevated, but absolute CDT level was not changed. The mean absolute CDT concentration was higher in anti-CCP positive patients than that in anti-CCP negative. CDT (absolute and relative concentration) did not correlate with anti-CCP and RF. However, serum RF significantly correlated with anti-CCP. %CDT did not correlate with anti-CCP, but absolute level correlated with anti-CCP only in anti-CCP negative and RF negative patients. CDT did not correlate with RF, but solely with anti-CCP in anti-CCP negative patients. Anti-CCP correlated with DAS 28 only in anti-CCP negative RA, but CDT (absolute and relative units) correlated with DAS 28 in all patients and in anti-CCP positive RA.

These results suggest that the changes in CDT and anti-CCP concentrations are not associated with oneself and indicate on the independence of these posttranslational modifications in rheumatoid arthritis. Only the alterations in transferrin glycosylation reflected the activity of RA.

Population-based osteoarthritis (OA) cohorts provide vital data on risk factors and outcomes of OA, however the methods to define OA vary between cohorts. We aimed to provide recommendations for combining knee and hip OA data in extant and future population cohort studies, in order to facilitate informative individual participant level analyses. International OA experts met to make recommendations on: 1) defining OA by X-ray and/or pain; 2) compare The National Health and Nutrition Examination Survey (NHANES)-type OA pain questions; 3) the comparability of the Western Ontario & McMaster Universities Osteoarthritis Index (WOMAC) scale to NHANES-type OA pain questions; 4) the best radiographic scoring method; 5) the usefulness of other OA outcome measures. Key issues were explored using new analyses in two population-based OA cohorts (Multicenter Osteoarthritis Study; MOST and Osteoarthritis Initiative OAI). OA should be defined by both symptoms and radiographs, with symptoms alone as a secondary definition. Kellgren and Lawrence (K/L) grade ≥2 should be used to define radiographic OA (ROA). The variable wording of pain questions can result in varying prevalence between 41.0% and 75.4%, however questions where the time anchor is similar have high sensitivity and specificity (91.2% and 89.9% respectively). A threshold of 3 on a 0-20 scale (95% CI 2.1, 3.9) in the WOMAC pain subscale demonstrated equivalence with the preferred NHANES-type question.

This research provides recommendations, based on expert agreement, for harmonising and combining OA data in existing and future population-based cohorts.

To confirm altered perfusion within tibial bone marrow lesions (BMLs) and improve our understanding on the relationship between BMLs and pain in knee osteoarthritis (OA). Participants with moderate to severe knee OA were recruited and pain was assessed using the pain subscale of the Western Ontario and McMaster Universities Arthritis Index (WOMAC). Subchondral tibial BMLs were identified and graded on magnetic resonance imaging (MRI) proton density-weighted (PDW) fat suppressed images. A pharmacokinetic model was used to analyze perfusion parameters on dynamic contrast enhanced (DCE) MRI which represent transfer rates in and out of the BMLs. The relation between perfusion and pain was evaluated using multivariable linear regression after adjustment for BML grade, age, gender and body mass index (BMI). There were 37 participants (mean age 64.9 years, range 46-86) with radiographic Kellgren and Lawrence grades of 3 and 4 in the study knee; 75.6% had BMLs that were classified grades 1 and 2. The mean WOMAC pain score was 10.3 (0-20 scale). There was a significant correlation between BML K(el) (rate of contrast elimination) and BML grade (P = 0.001 univariate, P = 0.002 multivariate analyses), although we did not demonstrate any significant multivariate association between BML perfusion and pain. We also found an inverse relationship between pain at sleep and BML grade (P < 0.05).

The absence of any significant association between bone perfusion and pain implies that the relationship of tibial BMLs to pain in OA is still incompletely understood. BMLs are just one component of the whole knee joint and are formed from various causes, all of which interact and collectively contribute to the genesis of pain in OA.

To review the specific mechanism of action of biologic response modifiers and help clinicians place these new drugs in the context of established therapies for rheumatoid arthritis (RA). Review of scientific literature, including all the clinical trials for these drugs. Referral to a rheumatologist should be strongly considered as soon as the diagnosis of RA is made. Early referral to a specialist has been associated with improved health status for patients with RA due to early and aggressive therapy with these new agents.

Biologic response modifiers target key inflammatory events involved in joint destruction. They have the potential to revolutionize the management of RA.

To determine the feasibility, reliability and validity of the childhood health assessment questionnaire--modified for Arab children (CHAQ--MAC). One hundred and eighteen modified questionnaires were completed by 75 juvenile rheumatoid arthritis (JRA) patients and their parents attending the Pediatric Rheumatology Clinic at the King Faisal Specialist Hospital and Research Centre, Riyadh, Kingdom of Saudi Arabia over an 18 month period (January 1996 to May 1997). The modified questionnaire was self-administered by 82% of the parents. The median time to complete the questionnaire was 10 minutes. The main difficulty in comprehension was discomfort dimension (visual analogue scale [VAS] and morning stiffness). Test retest reliability was good (r=0.79). Validity of the CHAQ-MAC was confirmed by the strong correlation between disability index and VAS score (r=0.58). Functional activities that caused the most difficulties were cross sitting, assuming the prayer position, and using the Arabic style toilet.

The modified CHAQ is a suitable assessment tool for Arab children suffering from JRA.

We aimed to investigate whether abatacept used in patients for RA was associated with an increased risk of reporting overall cancer and specific cancers, including breast, lung, lymphoma, melanoma and non-melanoma skin cancer when compared with other biologic DMARDs (bDMARDs). We performed an observational study within VigiBase, the World Health Organization's global database of individual case safety reports, from 2007 to 2017 to compare the cases of cancer reported in RA patients exposed to abatacept with those reported in RA patients exposed to other bDMARDs. We conducted disproportionality analyses allowing the estimation of reporting odds ratios (RORs) with 95% CIs of the exposure odds among spontaneous reporting of cancers to the exposure odds among other reported adverse effects. We identified 15 846 adverse effects reported in RA patients who received abatacept and 290 568 adverse effects reported in RA patients treated with other bDMARDs. Compared with other bDMARDs, the use of abatacept was not associated with an increased risk of reporting cancer overall [ROR 0.98 (95% CI 0.91, 1.05)]. Analyses by specific cancer sites showed a significantly increased ROR for melanoma [1.58 (95% CI 1.17, 2.08)], but not for other specific cancer sites. ClinicalTrials.gov (http://clinicaltrials.gov), NCT03980639.

Compared with other bDMARDs, exposure to abatacept in RA patients was only significantly associated with an increased risk of reporting melanoma. This increased risk is consistent with the properties of abatacept (CTLA-4 agonist) since it has an opposite action than ipilimumab, an antibody that blocks CTLA-4 and is approved for the treatment of malignant melanoma.

Osteoarthritis (OA) is the leading cause of musculoskeletal pain and functional disability worldwide. However, the etiology of this condition is still largely unknown. We report the clinical course of an elderly man with knee OA.

Plain radiographs and MRI examinations performed during follow-up suggested that the pathophysiology of the patient's knee OA and joint pain may have been primarily due to bone alterations.

To evaluate the performance of biochemical and traditional markers in predicting radiographic progression in rheumatoid arthritis (RA). One hundred thirty-two patients with early RA were treated with nonbiologic therapies for 2 years and studied longitudinally. Genomic DNA was analyzed for presence of the shared epitope. Levels of matrix metalloproteinases (matrix metalloproteinase 1 [MMP-1], MMP-13, and MMP-3), tissue inhibitor of metalloproteinases 1 (TIMP-1), and cartilage oligomeric matrix protein (COMP) were assessed in serially obtained serum samples. The presence of pyridinoline (Pyr), deoxypyridinoline, glycosylated Pyr (Glc-Gal-Pyr), and C-telopeptide of type II collagen (CTX-II) was assessed in urine samples. Radiographs obtained at entry and at 2 years were evaluated using the modified Larsen score. Baseline and 2-year radiographs were available from 118 patients. Larsen scores worsened during the 2 years in 50 patients, while 68 patients had no radiographic progression. Levels of a variety of biochemical markers, i.e., MMP-3, CTX-II, COMP, TIMP-1, Pyr, and Glc-Gal-Pyr, correlated significantly with radiographic progression at entry and longitudinally as assessed by area under the curve (AUC). By multivariate analysis, a model including MMP-3 and CTX-II was identified as providing the best prediction of radiographic progression at entry (predictive accuracy by receiver operating characteristic [ROC] AUC = 0.76 [95% confidence interval 0.66-0.85]), while a combination of MMP-3, CTX-II, and swollen joint count formed the best longitudinal AUC model (predictive accuracy by ROC AUC = 0.81 [95% confidence interval 0.73-0.89]). Patient-reported measures (Health Assessment Questionnaire, pain scores) were of limited use. In a subset of 50 patients who were treated with methotrexate (MTX) during the followup period, median serum MMP-3 levels decreased after the initiation of MTX therapy (P = 0.0003).

These results indicate that biochemical markers are useful predictors of radiographic progression in RA and that serum MMP-3 levels decrease significantly with MTX therapy. Multivariate models that include MMP-3 and CTX-II perform better than existing traditional markers in predicting radiographic outcome in RA.

Internalised stigma is theorized to be the internalisation and legitimisation of stereotypes of the diagnosis held in society and has not been quantified within patients with Rheumatoid Arthritis. This study aimed to: validate a modified version of a measure of internalised stigma, (the Internalised Stigma of Mental Illness scale, ISMI) for use in a group of patients diagnosed with rheumatoid arthritis; establish the consistency of the construct being measured, and to explore the levels of internalised stigma within this group. A cross-sectional survey was conducted in London, UK with participants receiving out-patient treatment for Rheumatoid Arthritis. Participants completed the ISMI-Rheumatoid Arthritis (ISMI-RA) and a measure of self-esteem. One hundred respondents were interviewed by phone. The ISMI-RA was found to be reliable using a measure of internal consistency (α = 0.85) showed concurrent validity with the Index of Self Esteem (r = 0.58, p < 0.01) and discriminant validity with no association with gender (t = 1.43, p = 0.61). A quarter of respondents reported internalised stigma to a 'severe' level. Acceptability and feasibility were established. A confirmatory factor analysis provided some support for the model of internalised stigma.

The application of the ISMI-RA among the Rheumatoid Arthritis population looks promising. Internalised stigma was found to be present within this group. More research is needed to generalize these results and to explore the effects of internalised stigma on treatment adherence and quality of life.

Gout is the most common cause of inflammatory arthritis in men aged >40 years and is frequently encountered in clinical practice. The goal of this article was to review the published literature on the epidemiology, treatment, and estimated burden of illness of acute gout. Articles on gout published in English between 1980 and June 2002 were identified through a MEDLINE search. Relevant clinical studies and review articles were found using the text- and keyword-search term gout alone and in combination with epidemiology, prevalence, incidence, complications, outcome, quality of life, economics, cost, prevention or drug therapy. The reference lists of identified articles, especially review articles, were checked for any additional studies that might have been missed in the original MEDLINE search. The epidemiology of gout in various geographic regions has been well documented. Data suggest that environmental, racial, and hereditary factors may influence the development of gout, and that the prevalence of gout appears to be on the rise worldwide. Evidence from well-designed clinical studies evaluating drug therapies for gout is limited. Therapies for acute gout include corticotropin, corticosteroids, colchicine or, more often, nonsteroidal anti-inflammatory drugs (NSAIDs), which have shown comparable efficacy. A recent study suggests that etoricoxib, a new cyclooxygenase-2-selective inhibitor, may be as effective as and better tolerated than traditional NSAIDs in the treatment of gout. Urate-lowering therapy, prophylactic colchicine, and low-dose NSAIDs are used for the long-term prophylaxis of gout. However, all acute and prophylactic therapies are associated with adverse events. Using an economic model for gout, the annual direct burden of illness for new cases of acute gout can be estimated at 27,378,494 US dollars in the United States.

Gout is an increasingly prevalent condition worldwide and creates a heavy economic burden. Available treatments are generally effective; however, they are not devoid of adverse events. Well-designed, long-term, controlled clinical trials evaluating the comparative efficacy and tolerability of treatments for gout are needed.

To investigate the clinical characteristics of rheumatoid arthritis (RA) patients with malignant tumor. Retrospective summary was made of 1 562 in patients of RA from January 2011 to June 2017. In the study, 74 RA patients with malignant tumor were reviewed and analyzed, and the general conditions, tumor types, RA and tumor onset sequence, and the medication situation were analyzed. The incidence of malignant tumor in the patients with rheumatoid arthritis in our center was 4.16%. The 74 patients were complicated with malignant tumor, of whom 53 were female, and 21 male. The age of RA at presentation was (52.6±17.8) years. The average disease duration of malignant tumor was (63.4 ± 12.7) years. The onset time of rheumatoid arthritis was earlier than that of malignant tumors in 51 cases (51/74), with an average of (17.2±14.2) years between 2 and 60 years. The incidence of malignant tumor was earlier than that of rheumatoid arthritis in 16 cases (16/74), with an average of (6.2±5.9) years between 1 and 21 years, of which 10 cases were sex hormone related tumors. Seven cases (7/74) were diagnosed with RA at the same time, and the time interval between the two diseases was within 1 year. All the patients were over 60 years old with digestive tract tumors. All the 7 patients showed polyarthritis, significantly increased erythrocyte sedimentation rate and C-reactive protein, including 4 rheumatoid factor positive cases and 2 anti-CCP antibody positive cases. The effect of non-steroidal anti-inflammatory drugs and traditional drugs to improve the condition of the disease was poor in the 7 patients, and the condition was relieved after using low-dose glucocorticoids. Gastrointestinal tumors, breast and reproductive system tumors were the most common, followed by respiratory, urological and blood system tumors.

The risk in patients of rheumatoid arthritis complicated with malignant tumor is higher than that of the general population. A variety of factors play an important role in cancer risk of RA, including disease activity, some estrogen metabolites, the use of drugs and so on. Therefore, all RA patients should be screened for malignant tumor during diagnosis, and malignant tumor surveillance is mandatory for all rheumatoid arthritis patients after diagnosis.

Autologous chondrocyte implantation (ACI) has a failure rate of approximately 20%, but it is yet to be fully understood why. Biomarkers are needed that can pre-operatively predict in which patients it is likely to fail, so that alternative or individualised therapies can be offered. We previously used label-free quantitation (LF) with a dynamic range compression proteomic approach to assess the synovial fluid (SF) of ACI responders and non-responders. However, we were able to identify only a few differentially abundant proteins at baseline. In the present study, we built upon these previous findings by assessing higher-abundance proteins within this SF, providing a more global proteomic analysis on the basis of which more of the biology underlying ACI success or failure can be understood. Isobaric tagging for relative and absolute quantitation (iTRAQ) proteomic analysis was used to assess SF from ACI responders (mean Lysholm improvement of 33; n = 14) and non-responders (mean Lysholm decrease of 14; n = 13) at the two stages of surgery (cartilage harvest and chondrocyte implantation). Differentially abundant proteins in iTRAQ and combined iTRAQ and LF datasets were investigated using pathway and network analyses. iTRAQ proteomic analysis confirmed our previous finding that there is a marked proteomic shift in response to cartilage harvest (70 and 54 proteins demonstrating ≥ 2.0-fold change and p < 0.05 between stages I and II in responders and non-responders, respectively). Further, it highlighted 28 proteins that were differentially abundant between responders and non-responders to ACI, which were not found in the LF study, 16 of which were altered at baseline. The differential expression of two proteins (complement C1s subcomponent and matrix metalloproteinase 3) was confirmed biochemically. Combination of the iTRAQ and LF proteomic datasets generated in-depth SF proteome information that was used to generate interactome networks representing ACI success or failure. Functional pathways that are dysregulated in ACI non-responders were identified, including acute-phase response signalling.

Several candidate biomarkers for baseline prediction of ACI outcome were identified. A holistic overview of the SF proteome in responders and non-responders to ACI  has been profiled, providing a better understanding of the biological pathways underlying clinical outcome, particularly the differential response to cartilage harvest in non-responders.

Chronic inflammation, as seen in gout, may contribute to an increased risk of developing cardiovascular (CV) events (CVE). The aim of the study was to explore the effect of adding gout as a chronic inflammatory disease to the Dutch SCORE, a tool predicting 10-year CV mortality and morbidity. This was a cross-sectional substudy including new patients with gout according the 2015 EULAR/ACR classification criteria who had participated in a trial on diagnostic accuracy of DECT with mono or oligoarthritis. Patients underwent a structured CV consultation, including assessment of CVE-history and of CV risk factors with the Dutch risk prediction SCORE. Chi-square test for trends was used to test for significance reclassification of the CV risk before and after adding gout to the Dutch SCORE. Seventy-six gout patients were included. SCORE was applied in 60 patients; 16 patients had experienced a prior CVE. The 10-year risk scores without gout as risk factor were high in 29 patients (48.3%), moderate in 6 (10%) and low in 25 (41.7%); with gout, the risk of 23/60 patients (38.3%) was reclassified from low to moderate in 6 patients (10%), from low to high in 11 (18.3%) and from moderate to high in 6 (10%), p<0.001 for trend.

Adding gout to the risk prediction tools led to significant and clinically relevant reclassification of CV risk in new gout patients. Studies with large follow-up are warranted to validate these findings.

Polymyalgia rheumatica (PMR) is characterised by inflammatory pain of shoulders and the pelvic girdle that affects older people. Conditions that can mimic PMR include rheumatoid arthritis (RA), spondyloarthritis (SpA) and calcium pyrophosphate disease (CPPD). In this study, we aimed to define the prevalence of CPPD among patients with polymyalgic syndrome with suspected PMR according to recent ACR/EULAR criteria. This was an observational study in which we included patients with polymyalgic syndrome (inflammatory pain of shoulders, elevated C-reactive protein (CRP) level, and age >50 years). All patients were tested for RA antibodies and underwent ultrasonography (US) of shoulders [gleno-humeral effusion, biceps tenosynovitis, sub-acromiodeltoid (SAD) bursitis, synovitis and CPPD of the acromio-clavicular (AC) joint and humeral bone erosion]. We included 94 patients with polymyalgic syndrome (mean age 69.4±11.3 years, 67% female); 27 had a diagnosis of RA and 14 SpA. The remaining 52 were considered to have PMR according to ACR/EULAR criteria for PMR; 25 had a diagnosis of CPPD. As compared with PMR patients without CPPD, those with CPPD more frequently had humeral bone erosion (p=0.003), synovitis and CPPD of the AC joint (p<0.0001 for both) and less frequently SAD bursitis (p=0.0098). For PMR diagnosis, the most sensitive US features were SAD bursitis (96.3%) and biceps tenosynovitis (85.2%), despite low specificity. For CPPD diagnosis, CPPD of the AC joint had the best ratio of sensitivity to specificity (sensitivity: 85.2%; specificity: 97.1%).

Detection of CPPD is relatively frequent with suspected PMR. Adding US assessment of the AC joint to usual US screening might help the clinician better distinguish PMR from other conditions, notably CPPD.

It has been suggested that elevated mean red cell volume (MCV) may be a predictor of haematological toxicity in rheumatoid arthritis (RA) patients receiving methotrexate (MTX). We wished to identify whether there was an association between MCV, red cell folate and haematological toxicity in patients on MTX monotherapy for the long-term management of RA. Evidence of haematological toxicity was sought by note review of patients recruited in a cross-sectional study of MTX monotherapy in RA. Retrospective data included MCVs from before MTX initiation and after 3 and 6 months of treatment. Data were collected prospectively every 6 months for up to 2 years after enrolment. Any record of cytopenia or the development of haematological malignancy was recorded from commencement of MTX until the present day. Red cell folate concentrations were tested on enrolment to the study. A total of 165 patients was included, 74.5% female, median disease duration 7 years (range 3 months-57 years). The median duration of MTX treatment was 74.9 months (range 10-241 months) giving 1030.2 patient-years of MTX exposure. Twenty-four patients (14.5%) had a MCV > 98 fL on study entry. Evidence of haematological abnormality was found in six patients (3.6%); chronic lymphocytic leukaemia (1), persistent lymphocytosis (1), persistent monocytosis (1) and neutropenia (3). There was no association between red cell folate or MCV and haematological toxicity.

Neutropenia and pancytopenia are rare side-effects of MTX therapy in this cohort. Elevated MCV or low mean red cell folate does not appear to be associated with haematological malignancy or toxicity in this cohort of patients on long-term MTX therapy.

Rheumatoid arthritis (RA) is chronic, painful, disabling condition resulting in significant impairments in physical, emotional, and social health. We used different methods and perspectives to evaluate the responsiveness of PROMIS® short forms (SFs) and identify minimal and meaningful score changes. Adults with RA enrolled in a multi-site prospective observational cohort completed PROMIS Physical Function, Pain Interference, Fatigue, Participation in Social Roles/Activities SFs, PROMIS-29, and pain, patient global, and rated change in specific symptoms and RA (a little vs. lot better or worse) at the second visit. Physicians recorded joint counts, MD Global Assessment, and change in RA at visit 2. We compared mean score differences for minimal and meaningful improvement/worsening using patient and MD change ratings and distribution-based methods, and visually inspected empirical cumulative distribution function curves by change categories. The 348 adults were mostly (81%) female with longstanding RA. Using patient ratings, generally 1-3 point differences were observed for minimal change and 3-7 points for meaningful change. Larger differences were observed with patient vs. physician ratings and for symptom-specific vs. RA change. Mean differences were similar among SF versions. Prespecified hypotheses about change in PROMIS Physical Function, Pain Interference, Fatigue and Participation and legacy scales were supported.

PROMIS SFs and the PROMIS-29 Profile are responsive to change and generally distinguish between minimal and meaningful improvement and worsening in key RA domains. These data add to a growing body of evidence demonstrating robust psychometric properties of PROMIS and supporting use in RA care, research, and decision-making.

The ANP32A gene encodes a tumor suppressor molecule that plays a regulatory role in apoptosis and interferes with canonical Wnt signaling in vitro. We undertook this study to test whether genetic variation at ANP32A was associated with osteoarthritis (OA) in women. Single-nucleotide polymorphisms (SNPs) in the ANP32A gene were genotyped in 438 control women, 425 women with total knee replacements (TKRs), and 537 women with total hip replacements (THRs) from the Nottingham case-control study as well as in 820 women from the population-based Chingford Study cohort for whom hip and knee radiographs were available. The most highly associated SNP was further tested in women from the Rotterdam Study (131 with THRs, 633 with knee OA, and 1,567 controls) and the TwinsUK Study cohort (67 with THRs, 43 with TKRs, and 358 controls), for a total of 2,170 patients with OA and 2,849 controls. The ANP32A transcript was abundantly expressed in normal and OA articular cartilage. Three SNPs in the ANP32A gene were significantly associated in Nottingham patients with hip OA, but not knee OA. One of these (rs7164503) was associated with hip and knee OA in the Chingford Study cohort and with THR in the TwinsUK Study cohort, but the association was not statistically significant in the Rotterdam Study. When we combined hip data from all 4 cohorts, we found that the minor allele of rs7164503 was associated with a significantly lower risk of hip OA (Mantel-Haenszel odds ratio 0.67 [95% confidence interval 0.53-0.84], P < 3.8 x 10(-4)) and that a similar trend was observed for knee OA (Mantel-Haenszel odds ratio 0.87 [95% confidence interval 0.73-1.01], P < 0.055).

Our results provide evidence suggesting that ANP32A is involved in the pathogenesis of OA of the hip.

To study injection site reactions (ISRs) associated with etanercept therapy. Retrospective chart review, along with prospective analysis of selected patients experiencing ISRs associated with etanercept therapy. Academic rheumatology/immunology unit and dermatology clinic. Patients with rheumatoid arthritis, juvenile rheumatoid arthritis, inflammatory seronegative arthritis, psoriatic arthritis, psoriasis, or inflammatory bowel disease. Skin biopsy specimens were taken from selected patients experiencing ISRs. Incidence of IRSs and histological and immunophenotypic analysis of ISRs in 3 patients undergoing prospective study. Twenty-one (20%) of 103 of all patients receiving etanercept reported ISRs, all within the first 2 months of inception of therapy. The reactions occurred 1 to 2 days after the last injection and resolved within a few days. Moreover, eventual waning of reactions was observed, with none proving to be dose limiting. Histological examination of all biopsy specimens showed an inflammatory infiltrate composed of predominantly lymphoid cells and some eosinophils, in a perivascular cuffing pattern, without evidence of leukocytoclastic vasculitis. The infiltrating lymphoid cells were predominantly activated mature (HLA-DR(+)/CD3(+)/CD4(-)/CD8(+)) cytotoxic T lymphocytes, with a small number of CD4(+) cells. A biopsy specimen from a recall ISR showed strong HLA-DR expression by epidermal keratinocytes.

Injection site reactions associated with etanercept therapy are common, and may be an example of a T-lymphocyte-mediated delayed-type hypersensitivity reaction, with waning over time due to eventual induction of tolerance.

The proenzyme of matrix metalloproteinase 7 (proMMP-7), which can degrade various extracellular matrix (ECM) and non-ECM molecules after being activated, is overexpressed in osteoarthritic (OA) articular cartilage, but the process of its activation in the cartilage remains unknown. The present study was undertaken to investigate the expression of tetraspanin CD151 in OA cartilage and its involvement in proMMP-7 activation. The expression of CD151 in articular cartilage was examined by reverse transcription-polymerase chain reaction (RT-PCR), real-time PCR, immunohistochemistry, in situ hybridization, and immunoblotting. Chondrocytes were used to study the interaction between CD151 and proMMP-7, and activation of proMMP-7. RT-PCR revealed expression of CD151 messenger RNA in all OA cartilage samples, but in only 30% of normal control cartilage samples. Immunohistochemistry and in situ hybridization findings indicated that CD151 was coexpressed with proMMP-7 in chondrocytes, mainly in the superficial and transitional zones of OA cartilage. CD151 immunoreactivity directly correlated with the Mankin score (r = 0.757, P < 0.0001 [n = 30]) and the degree of chondrocyte cloning (r = 0.83, P < 0.0001 [n = 30]) in the cartilage samples. Complexes CD151 and proMMP-7 and their colocalization on the cell membranes were demonstrated by immunoprecipitation and double fluorescence immunostaining of the OA chondrocytes. In situ zymography indicated that chondrocytes exhibit pericellular proteolytic activity, which was abolished by treatment with MMP inhibitors, anti-MMP-7 antibody, or anti-CD151 antibody.

These data demonstrate that CD151 is overexpressed in OA cartilage and suggest that CD151 plays a role in the pericellular activation of proMMP-7, leading to cartilage destruction and/or chondrocyte cloning.

Age is an important factor in the development of osteoarthritis. Microarray studies provide insight into cartilage aging but do not reveal the full transcriptomic phenotype of chondrocytes such as small noncoding RNAs, pseudogenes, and microRNAs. RNA-Seq is a powerful technique for the interrogation of large numbers of transcripts including nonprotein coding RNAs. The aim of the study was to characterise molecular mechanisms associated with age-related changes in gene signatures. RNA for gene expression analysis using RNA-Seq and real-time PCR analysis was isolated from macroscopically normal cartilage of the metacarpophalangeal joints of eight horses; four young donors (4 years old) and four old donors (>15 years old). RNA sequence libraries were prepared following ribosomal RNA depletion and sequencing was undertaken using the Illumina HiSeq 2000 platform. Differentially expressed genes were defined using Benjamini-Hochberg false discovery rate correction with a generalised linear model likelihood ratio test (P < 0.05, expression ratios ± 1.4 log₂ fold-change). Ingenuity pathway analysis enabled networks, functional analyses and canonical pathways from differentially expressed genes to be determined. In total, the expression of 396 transcribed elements including mRNAs, small noncoding RNAs, pseudogenes, and a single microRNA was significantly different in old compared with young cartilage (± 1.4 log2 fold-change, P < 0.05). Of these, 93 were at higher levels in the older cartilage and 303 were at lower levels in the older cartilage. There was an over-representation of genes with reduced expression relating to extracellular matrix, degradative proteases, matrix synthetic enzymes, cytokines and growth factors in cartilage derived from older donors compared with young donors. In addition, there was a reduction in Wnt signalling in ageing cartilage.

There was an age-related dysregulation of matrix, anabolic and catabolic cartilage factors. This study has increased our knowledge of transcriptional networks in cartilage ageing by providing a global view of the transcriptome.

To investigate demographic, symptom-related, and cognitive determinants of cane use for knee osteoarthritis (OA) and prioritize the factors that could facilitate cane use in people with no previous cane use. A survey of people ages ≥45 years with a clinical diagnosis of knee OA was conducted. The survey consisted of the following two sections: 1) demographic and cognitive determinants of cane use assessed via subscales of the Cane Cognitive Mediator Scale, and 2) 19 statements, underpinned by the Behaviour Change Wheel theoretical framework, relating to factors that could facilitate regular cane use. Logistic regression was used to examine determinants of cane use, while a priority pairwise ranking activity (1000minds software) determined the rank order of the 19 statements that could facilitate cane use. A total of 529 people completed Part 1 (80% females; 35% cane users) and 231 people completed Part 2. Age (odds ratio [OR] 1.06, 95% confidence interval [95% CI] 1.03- 1.09), body mass index (BMI) (OR 1.03, 95% CI 1.01-1.06), knee pain ≥3 years (OR 2.62, 95% CI 1.63-4.21) and numeric rating scale pain level while walking (OR 1.19, 95% CI 1.09-1.30) were significant independent determinants of cane use. In people who had never used a cane, statements relating to cane-use technique, fitting, knowledge of benefits, and motivation were ranked highest overall.

Independent determinants of cane use include older age, higher BMI, greater pain duration, and greater severity of knee pain. Strategies targeting an individual's capability and motivation to use a cane may increase cane use among people with knee OA.

Minimal invasion surgery (MIS) is a recent technique recommended for Total knee arthroplasty (TKA) but demands an effort of the surgeons and the learning curve may be long. Twenty six MIS-TKA were matched to 36 standard TKA with respect to age, sex, body mass index or preoperative score. All patients suffered from knee osteoarthritis, which had not improved with medical treatment and which presented a less than 10 degrees deformity in the coronal and sagittal radiographic projections. At six months after the surgery a specific questionnaire was completed as well as the KSS (Knee Society rating scale), the generic short-form health questionnaire (SF-12) and a visual analogue scale (VAS). The MIS technique required more time of surgery (p < 0.001), hospital stay was noticeably shorter (p < 0.05) and drainage volume collected after surgery was significantly higher in the standard technique. We observe a higher frequency in small sizes implants for MIS surgery but no statistically significant differences were found between both groups regarding the radiological alignment of the implant. At six months no differences were found between the groups in range of motion, KSS scores, the physical or mental subscale SF-12, patient's pain perception, satisfaction or subjective improvement.

Minimal invasion surgery in total knee arthroplasty showed no improvement over a standard approach.

Nonpharmacologic interventions are themselves complex and are often combined with drugs and other interventions in the treatment of rheumatic diseases. Therefore, overall strategies for treatment are complex interventions. These should be evaluated regarding their processes and outcomes. The CARE network, an international organization of health professionals (physicians and nonphysicians) and patients conducted a survey in 2008 to identify core outcomes in the ICF perspective, completed with a second survey (2009-2010) with patients in routine practice. These surveys have provided new information about domains to investigate as a basis for evaluating complex interventions. Outcome Measures in Rheumatology Clinical Trials (OMERACT) participants in this Special Interest Group agreed that current outcomes used in pharmacological research are not sufficient if the nonpharmacologic independent or combined contributions are to be assessed; other domains need to be addressed. This is an area of interest for further development.

Recommendations are proposed to develop research in the area of outcome for evaluation of complex interventions in rheumatic diseases.

Guidelines for the management of rheumatoid arthritis (RA) recommend using influenza and pneumococcal vaccinations to mitigate infection risk. The level of adherence to these guidelines is not well known in the UK. The aims of this study were to describe the uptake of influenza and pneumococcal vaccinations in patients with RA in the UK, to compare the characteristics of those vaccinated to those not vaccinated and to compare vaccination rates across regions of the UK. A retrospective cohort study of adults diagnosed with incident RA and treated with non-biologic immunosuppressive therapy, using data from a large primary care database. For the influenza vaccination, patients were considered unvaccinated on 1st September each year and upon vaccination their status changed to vaccinated. For pneumococcal vaccination, patients were considered vaccinated after their first vaccination until the end of follow-up. Patients were stratified by age 65 at the start of follow-up, given differences in vaccination guidelines for the general population. Overall (N=15,724), 80% patients received at least one influenza vaccination, and 50% patients received a pneumococcal vaccination, during follow-up (mean 5.3 years). Of those aged below 65 years (N=9,969), 73% patients had received at least one influenza vaccination, and 43% patients received at least one pneumococcal vaccination. Of those aged over 65 years (N=5,755), 91% patients received at least one influenza vaccination, and 61% patients had received at least one pneumococcal vaccination. Those vaccinated were older, had more comorbidity and visited the GP more often. Regional differences in vaccination rates were seen with the highest rates in Northern Ireland, and the lowest rates in London.

One in five patients received no influenza vaccinations and one in two patients received no pneumonia vaccine over five years of follow-up. There remains significant scope to improve uptake of vaccinations in patients with RA.

Little is known of the effectiveness of nonpharmacological interventions for fibromyalgia syndrome (FMS). The authors therefore carried out a systematic review from 1980 to May 2000 of randomized controlled trials (RCTs) of nonpharmacological interventions for FMS. A search of computerized databases was supplemented by hand searching of bibliographies of key publications. The methodological quality of studies included in the review was evaluated independently by two researchers according to a set of formal criteria. Discrepancies in scoring were resolved through discussion. The review yielded 25 RCTs, and the main categories of interventions tested in the studies were exercise therapy, educational intervention, relaxation therapy, cognitive-behavioral therapy, acupuncture, and forms of hydrotherapy. Methodological quality of studies was fairly low (mean score = 49.5/100). Most studies had small samples (median for individual treatment groups after randomization = 20), and the mean power of the studies to detect a medium effect ( > or = 0.5) was 0.36. Sixteen studies had blinded outcome assessment, but patients were blinded in only 6 studies. The median longest follow-up was 16 weeks. Statistically significant between-group differences on at least one outcome variable were reported in 17 of the 24 studies.

The varying combinations of interventions studied in the RCTs and the wide range of outcome measures used make it hard to form conclusions across studies. Strong evidence did not emerge in respect to any single intervention, though preliminary support of moderate strength existed for aerobic exercise. There is a need for larger, more methodologically rigorous RCTs in this area.

Fibromyalgia is a chronic disorder characterized by widespread pain and tenderness. Prior trials have demonstrated the efficacy of pregabalin for the relief of fibromyalgia symptoms, and it is approved for the treatment of fibromyalgia in the United States. However, prior to this study, there has not been a large-scale efficacy trial in patients with fibromyalgia in Japan. This randomized, double-blind, multicenter, placebo-controlled trial was conducted at 44 centers in Japan to assess the efficacy and safety of pregabalin for the symptomatic relief of pain in fibromyalgia patients. Patients aged ≥18 years who had met the criteria for fibromyalgia were randomized to receive either pregabalin, starting at 150 mg/day and increasing to a maintenance dose of 300 or 450 mg/day, or placebo, for 15 weeks. The primary efficacy endpoint was mean pain score at final assessment. Secondary endpoints included Patient Global Impression of Change (PGIC) together with measures of sleep, physical functioning and quality of life. A total of 498 patients (89% female) were randomized to receive either pregabalin (n = 250) or placebo (n = 248). Pregabalin significantly reduced mean pain score at final assessment (difference in mean change from baseline, compared with placebo -0.44; P = 0.0046) and at every week during the study (P <0.025). Key secondary endpoints were also significantly improved with pregabalin treatment compared with placebo, including PGIC (percentage reporting symptoms "very much improved" or "much improved", 38.6% vs 26.7% with placebo; P = 0.0078); pain visual analog scale (difference in mean change from baseline, compared with placebo -6.19; P = 0.0013); Fibromyalgia Impact Questionnaire total score (-3.33; P = 0.0144); and quality of sleep score (-0.73; P <0.0001). Treatment was generally well tolerated, with somnolence and dizziness the most frequently reported adverse events. ClinicalTrials.gov: NCT00830167.

This trial demonstrated that pregabalin, at doses of up to 450 mg/day, was effective for the symptomatic relief of pain in Japanese patients with fibromyalgia. Pregabalin also improved measures of sleep and functioning and was well tolerated. These data indicate that pregabalin is an effective treatment option for the relief of pain and sleep problems in Japanese patients with fibromyalgia.

To test the effect of patient-reported outcome (PRO)-based tele-health followup for tight control of disease activity in patients with rheumatoid arthritis (RA), and the differences between tele-health followup performed by rheumatologists or rheumatology nurses. A total of 294 patients were randomized (1:1:1) to either PRO-based tele-health followup carried out by a nurse (PRO-TN) or a rheumatologist (PRO-TR), or conventional outpatient followup by physicians. The primary outcome was a change in the Disease Activity Score in 28 joints (DAS28) after week 52. Secondary outcomes were physical function, quality of life, and self-efficacy. The noninferiority margin was a DAS28 score change of 0.6. Mean differences were estimated following per protocol, intent-to-treat (ITT), and multivariate imputation analysis. Overall, patients had low disease activity at baseline and end followup. Demographics and baseline characteristics were similar between groups. Noninferiority was established for the DAS28. In the ITT analysis, mean differences in the DAS28 score between PRO-TR versus control were -0.10 (90% confidence interval [90% CI] -0.30, 0.13) and -0.19 (90% CI -0.41, 0.02) between PRO-TN versus control. When including 1 yearly visit to the outpatient clinic, patients in PRO-TN had mean ± SD 1.72 ± 1.03 visits/year, PRO-TR had 1.75 ± 1.03 visits/year, and controls had 4.15 ± 1.0 visits/year. This included extra visits due to inflammatory flare.

Among RA patients with low disease activity or remission, a PRO-based tele-health followup for tight control of disease activity in RA can achieve similar disease control as conventional outpatient followup. The degree of disease control did not differ between patients seen by rheumatologists or rheumatology nurses.

Major salivary gland ultrasonography (SGUS) is a widely used imaging technique to evaluate salivary gland involvement in primary Sjögren syndrome (pSS). The aim of this study was to evaluate the relationship between SGUS, salivary flow rate (SFR) as an objective measure of the gland function, and oral health-related quality of life (OHRQOL) as a patient-reported outcome measure (PROM) in a pSS cohort. Sixty-six patients with pSS were examined by SGUS according to Hocevar and Milic scoring systems. Patients with inhomogeneity/hypoechoic areas with scores ≥ 2 in parotid and submandibular glands were classified separately as "severe glandular involvement." Further, oral health, SFR, and Oral Health Impact Profile-14 (OHIP-14) for OHRQOL were assessed. Both total Hocevar and Milic scores were higher in 21 pSS patients with low unstimulated whole salivary flow rate (U-WSFR) than 45 pSS patients without low U-WSFR (

High Milic and Hocevar SGUS scores are associated with reduced SFR and poor OHRQOL as a PROM. The inhomogeneity component of the SGUS score is associated with low U-WSFR and is an indicator of severely affected gland function.

To assess the performance of fat-suppressed fluid-sensitive MRI sequences compared to T1-weighted (T1w) / T2w sequences for the detection of Modic 1 end-plate changes on lumbar spine MRI. Sagittal T1w, T2w, and fat-suppressed fluid-sensitive MRI images of 100 consecutive patients (consequently 500 vertebral segments; 52 female, mean age 74 ± 7.4 years; 48 male, mean age 71 ± 6.3 years) were retrospectively evaluated. We recorded the presence (yes/no) and extension (i. e., Likert-scale of height, volume, and end-plate extension) of Modic I changes in T1w/T2w sequences and compared the results to fat-suppressed fluid-sensitive sequences (McNemar/Wilcoxon-signed-rank test). Fat-suppressed fluid-sensitive sequences revealed significantly more Modic I changes compared to T1w/T2w sequences (156 vs. 93 segments, respectively; p < 0.001). The extension of Modic I changes in fat-suppressed fluid-sensitive sequences was significantly larger compared to T1w/T2w sequences (height: 2.53 ± 0.82 vs. 2.27 ± 0.79, volume: 2.35 ± 0.76 vs. 2.1 ± 0.65, end-plate: 2.46 ± 0.76 vs. 2.19 ± 0.81), (p < 0.05). Modic I changes that were only visible in fat-suppressed fluid-sensitive sequences but not in T1w/T2w sequences were significantly smaller compared to Modic I changes that were also visible in T1w/T2w sequences (p < 0.05). · When the Modic classification was defined in 1988, T2w sequences were heavily T2-weighted and thus virtually fat-suppressed.. · Nowadays, the bright fat signal in T2w images masks edema-like changes.. · The conventional definition of Modic I changes is not fully applicable anymore.. · Fat-suppressed fluid-sensitive MRI sequences revealed more/greater extent of Modic I changes.. · Finkenstaedt T, Del Grande F, Bolog N et al. Modic Type 1 Changes: Detection Performance of Fat-Suppressed Fluid-Sensitive MRI Sequences. Fortschr Röntgenstr 2018; 190: 152 - 160. ZIEL:  Ziel der Studie ist es, die Detektionsrate von Modic-Typ-1-Endplattenveränderungen mittels fettgesättigten, flüssigkeitssensitiven MRT-Sequenzen gegenüber Standard T1- und T2-gewichteten Sequenzen an der Lendenwirbelsäule zu vergleichen. Sagittale T1, T2 und fettgesättigte, flüssigkeitssensitive MRT-Sequenzen von 100 Patienten (gesamt 500 Wirbelsegmente; 52 weiblich, Durchschnittsalter 74 ± 7,4 Jahre; 48 männlich, Durchschnittsalter 71 ± 6,3 Jahre) wurden retrospektiv untersucht. Das Vorhandensein (ja/nein) und die Ausdehnung (Likert-skalierte Höhen-, Volumen- und anteroposteriore Endplattenausdehnung) von Modic-1-Veränderungen auf T1/T2 gegenüber fettgesättigten, flüssigkeitssensitiven MRT-Sequenzen wurden analysiert (McNemar/Wilcoxon-signed-rank test). Mittels fettgesättigter, flüssigkeitssensitiver MRT-Sequenzen konnten signifikant mehr Modic-1-Veränderungen detektiert werden als mittels T1-/T2-Sequenzen (156 vs. 93 Segmente; p < 0,001). Die Ausdehnung von Modic-1-Veränderungen auf fettgesättigten, flüssigkeitssensitiven MRT-Sequenzen war signifikant größer gegenüber T1-/T2-Sequenzen (Höhe: 2,53 ± 0,82 vs. 2,27 ± 0,79, Volumen: 2,35 ± 0,76 vs. 2,1 ± 0,65, Endplattenausdehnung: 2,46 ± 0,76 vs. 2,19 ± 0,81), (p < 0,05). Modic-1-Veränderungen, die nur auf fettgesättigten, flüssigkeitssensitiven Sequenzen, aber nicht auf T1-/T2-Sequenzen detektiert werden konnten, waren signifikant kleiner im Vergleich zu Modic-1-Veränderungen, die auch auf T1-/T2-Sequenzen sichtbar waren (p < 0,05). Fettgesättigte, flüssigkeitssensitive Sequenzen haben nicht nur signifikant häufiger Modic-1-Veränderungen, sondern auch eine größere Ausdehnung ebendieser gegenüber Standard T1-/T2-Sequenzen nachweisen können. · Als die Modic-Klassifikation 1988 definiert wurde, waren T2-Sequenzen technisch bedingt nahezu fettgesättigt. · Fettsignal aktueller T2-Sequenzen ist deutlich heller, wodurch zusätzliches Knochenmarksödem maskiert werden kann. · Die ursprüngliche Definition von Modic-1-Veränderungen ist daher heutzutage nicht mehr zutreffend. · Fettgesättigte, flüssigkeitssensitive Sequenzen haben häufiger/größere Ausdehnung von Modic-1-Veränderungen gegenüber T1-/T2-Sequenzen nachweisen können.

In conclusion, fat-suppressed fluid-sensitive MRI sequences revealed significantly more Modic I end-plate changes and demonstrated a greater extent compared to standard T1w/T2w imaging.

Arthritis in the trapeziometacarpal joint of the thumb can cause swelling and loss of motion. Treatment options include arthrodesis, replacement arthroplasty and interposition arthroplasty. Our objective in this clinical study was to determine outcomes after trapezial arthroplasty with a silicone rubber implant and the relationship between self-reported and measured outcomes. At the Hand and Upper Limb Centre, St. Joseph's Hospital, London, Ont., a tertiary care centre, we reviewed a series of 26 patients with advanced osteoarthritis who underwent silicone rubber trapezial arthroplasty. The follow-up averaged 6.5 years. We assessed the outcomes subjectively, and by clinical, functional and radiographic examination. Although 88% of patients reported some improvement in pain and satisfaction, when quantified the improvement was less impressive: only 5.7 (on a visual analogue scale of 1-10, poor-excellent) for pain and 5.6 for satisfaction. Superior subjective results were reported by patients older than 60 years. Osteoarthritic changes had caused pronounced functional impairment in the hands of patients who underwent surgery and those who did not, so that any long-term benefit of surgery was not measurable. Patients had difficulty manipulating both small and large objects on the Jebsen's hand function test. Peri-implant and carpal radiographic lytic changes were observed in 90% of patients. Six patients (20%) required revision surgery (3 early, 3 late), including 1 with a pathologic scaphoid fracture.

Although clinical, functional and radiographic results were poor, they did not predict either satisfaction or pain improvement reported by patients, illustrating the need for a comprehensive standardized outcome evaluation to make informed decisions on the value of surgical intervention for osteoarthritis of the trapeziometacarpal joint.

To study joint damage severity in rheumatoid arthritis (RA) patients classified using ultrasound power Doppler (PD) and gray-scale (GS) joint inflammation outcomes and the 28-joint Disease Activity Score (DAS28). Ultrasound erosion scores were compared between (a) patients in group 1 (PD positive and GS ≥ median score), group 2 (PD negative and GS ≥ median score) and group 3 (PD positive and GS < median score) vs group 4 (PD negative and GS < median score) and (b) patients with high, moderate and low DAS28 scores vs those in DAS28 remission. Comparative analyses were performed using the 2-sample Student's t test. There were 1080 joints and 1800 joint recesses from 36 joints scanned in 30 RA adult patients (mean DAS28, 3.58; mean disease duration, 70.3 months) in this cross-sectional study. The mean and 95% CI ultrasound erosion scores were significantly higher (P = .026) for groups 1 (9.75, 6.69-12.81) vs 4 (3.4, 1.11-5.69) with a difference (95% CI) of 6.35 (0.78-11.83), but not significantly different (P values all > .05) for (a) groups 2 and 3 vs 4 and (b) patients with high, moderate and low DAS28 scores vs those in DAS28 remission.

Severity of ultrasound-detected bone erosions was significantly greater when both positive PD and a greater degree of GS joint inflammation were present in RA. This association was not observed when either component was absent. Single time point ultrasound joint inflammation assessment - and not DAS28 - is reflective of joint damage severity in RA patients.

To examine the effect of high dose corticosteroid pulse treatment (three times 200 mg dexamethasone intravenously in eight days) on calcium and bone metabolism in 17 consecutive patients with active rheumatoid arthritis (RA). Bone formation was quantified by measurement of serum alkaline phosphatase, osteocalcin, and carboxyterminal propeptide of type I procollagen (pro-I-CPP) concentrations. Bone resorption was measured by urinary excretion of calcium, hydroxyproline, (free and total) deoxypyridinoline (Dpyr), (free and total) pyridinoline (Pyr), and serum concentrations of the carboxyterminal cross linked telopeptide of type I collagen (I-CTP). Disease activity of RA was measured by erythrocyte sedimentation rate, C reactive protein, and Ritchie and Thompson joint scores. Disease activity was initially high, and decreased during corticosteroid pulse treatment and the following five weeks. Osteocalcin, alkaline phosphatase, and pro-I-CPP concentrations were initially within normal limits, while I-CTP, Dpyr, and Pyr were increased. Osteocalcin and pro-I-CPP concentrations decreased (p < 0.01) during corticosteroid pulse treatment, but rapidly returned to baseline after the treatment. No changes were observed in alkaline phosphatase and urinary excretion of calcium and hydroxyproline. Bone resorption measured by serum I-CTP and urinary excretion of Pyr and Dpyr was unchanged or decreased (p < 0.05-0.01), depending on the time of measurement and the parameter measured.

In these patients with active RA, bone resorption was increased, while bone formation was within normal limits. During high dose corticosteroid pulse treatment, bone formation was only transiently decreased, while markers of bone resorption were unchanged or decreased. Because corticosteroid pulse treatment has only a short term negative effect on bone formation, and because it probably reduces bone resorption, at least partly as a result of the decreased disease activity, the effect of corticosteroid pulse treatment on bone may be assumed to be relatively mild.

To investigate the effect of infliximab treatment on anti-cyclic citrullinated peptide antibodies (anti-CCP) and rheumatoid factor (RF) in patients with rheumatoid arthritis. 43 patients with rheumatoid arthritis not responding to disease modifying anti-rheumatic drugs (DMARD) received intravenous infliximab at a dose of 3 mg/kg at baseline and after two and six weeks, and subsequently bimonthly, in combination with methotrexate. Serum samples were collected at baseline and at week 24. A commercial enzyme linked immunosorbent assay was used to test for anti-CCP antibodies; RF were detected using a quantitative nephelometric assay. At baseline, 38 of the 43 patients (88%) were positive for anti-CCP antibodies, and 41 (95%) were positive for RF. The serum titre of anti-CCP and RF decreased significantly after six months of treatment (p = 0.0001 and p<0.0001, respectively). When the patients were grouped on the basis of their clinical response to infliximab, a significant decrease in serum anti-CCP antibodies and RF was observed only in patients who had clinical improvement (ACR 20 and ACR 50).

Anti-TNFalpha treatment in rheumatoid arthritis results in a decrease in the serum titres of RF and anti-CCP antibodies in patients showing clinical improvement, suggesting that these measurements may be a useful adjunct in assessing treatment efficacy.

C-reactive protein (CRP) is associated with increased risk for myocardial infarction, atherosclerosis, and peripheral artery diseases, while increased serum uric acid level is suggested to be independently associated with an increased risk of cardiovascular mortality. Accordingly, to investigate whether hyperuricemia is associated with serum CRP, we compared serum CRP levels between healthy subjects and patients with gout. In addition, we also examined whether benzbromarone has effects on serum CRP levels in patients with gout and the expression of CRP messenger RNA of CRP in the hepatoma cell line HuH7. In the first experiment, 40 healthy males and 43 male patients with gout were enrolled, then blood samples were drawn from each after an overnight fast. In the second experiment, 42 male patients with gout were given uric acid-lowering therapy with benzbromarone. Blood samples were drawn after an overnight fast before and 1 year after beginning benzbromarone treatment. In the third experiment, the effects of benzbromarone on IL1beta-induced CRP expression were determined in HuH7 cells. Log serum CRP levels were not significantly different between the patients with gout and healthy subjects, while log serum CRP levels were decreased by 11% after benzbromarone treatment, as compared to the values before treatment (p < 0.01). In addition, log serum adiponectin levels were elevated by 2% after treatment (p < 0.01). Furthermore, our in vitro findings demonstrated that benzbromarone down-regulated IL1beta-stimulated CRP gene expression.

These results suggest that hyperuricemia may not contribute to an increase in serum CRP level, while benzbromarone may have a favorable effect on CRP.

Although the geometry of the trochlear groove is considered important in the pathogenesis of patellofemoral joint pathology it is unclear how the shape of the trochlear groove relates to patella morphology. This cross-sectional study investigated the relationship between the shape of the trochlear groove and patella cartilage and bone morphology in healthy adults. Two hundred and ninety-seven healthy adults aged between 50 and 79 years with no clinical history of knee pain or pathology were examined using magnetic resonance imaging (MRI). From the magnetic resonance (MR) images, the bony angles formed at the distal and proximal trochlear groove were measured, together with patella cartilage and bone volumes and patella cartilage defects. After adjustment for potential confounders, there was an 8.70mm(3) (95% confidence interval (CI) 2.15, 15.26) increase in patella cartilage volume (P=0.009), with no increased prevalence of cartilage defects (odds ratio=0.99 (95% CI 0.96, 1.02), P=0.35), for every 1 degrees increase (i.e., as the angle became more flatter) at the distal trochlear groove. Moreover, there was a 53.86mm(3) (95% CI -90.26, -17.46) reduction in patella bone volume for every 1 degrees that the angle at the distal trochlear groove became more flattened (P=0.004). No significant association between the proximal trochlear groove angle and the patella cartilage or bone properties was observed.

A more flattened bony angle at the distal trochlear groove was associated with increased patella cartilage volume and reduced patella bone volume, but no increased prevalence of patella cartilage defects in adults with no history of knee pain or clinical disease. These cross-sectional findings suggest that a flattened distal trochlear groove may protect against degenerative patellofemoral conditions, such as osteoarthritis, but this will need to be confirmed in a longitudinal study.

Foot involvement is a major feature in rheumatoid arthritis (RA), leading to structural deformities. Methods to allow a 3-dimensional (3-D) evaluation of foot structure in RA to be applicable in daily clinical practice have not been evaluated. This study assessed the use of a foot digitizer, a noninvasive 3-D scanner collecting objective quantitative data of the feet, to evaluate the presence of foot structure abnormalities in an RA outpatient cohort. Foot digitizer data of RA patients were compared with healthy controls. Subanalyses were performed to find relationships with erosive disease and the presence of swollen and/or tender joints. Linear mixed models were applied with correction, including sex, age, body weight and height, foot length, Disease Activity Score in 28 joints, and disease duration. Forty-one percent of the patients showed >1 abnormal parameter, measured with the 3-D foot scanner. Most differences found were located in the forefoot, the most frequently affected area of the RA foot. Strikingly, even in the absence of joint erosions, marked alterations were found. Comparable differences were also observed between the patients with and without swollen and/or tender joints. Additionally, alterations were not strongly related to foot pain and disability, suggesting the capacity of the foot digitizer to detect early changes in foot structure.

The results highlight the impact of RA on foot structure, even in the absence of clinical signs of swelling or radiographic erosions. The foot digitizer offers a valuable tool to screen for such foot deformities before the presence of erosions.

Falls, associated injuries and fear-of-falling are common in adults with RA. Fear-of-falling can be a major consequence of, and as debilitating as falling, resulting in a cycle of activity restriction, reduced quality of life, institutionalisation and potentially increase risk of falls. The objective of this study was to examine the relationship between fear-of-falling and risk factors associated with fear-of-falling in adults with rheumatoid arthritis (RA) over a 1 year period. Five hundred fifty-nine patients with RA were recruited from four outpatient clinics in this prospective cohort study. Baseline assessments included socio-demographic, medical and lifestyle related risk factors. Fall incidence was prospectively obtained monthly using postal cards over a 1 year period. Fear-of-falling was assessed at baseline and 1 year using the Short Falls Efficacy Scale-International (Short FES-I). Logistic regression was used to determine the association between high fear-of-falling (Short FES-I > 11) at baseline (outcome) and a range of putative predictor variables including previous falls, and also baseline factors associated with a high fear-of-falling at follow-up. Five hundred thirty-five (ninety-six percent) participants (mean age 62.1 yrs.; 18-88 yrs) completed 1 year follow-up and of these, 254 (47%) completed the Short FES-I questionnaire at 1 year. In a multivariate model, a history of multiple falls (OR = 6.08) higher HAQ score (OR = 4.87) and increased time to complete the Chair Stand Test (OR = 1.11) were found to be independent predictors of high fear-of-falling and had an overall classification rate of 87.7%. There were no significant differences found in fear-of-falling at 1 year follow-up in those who reported falls during the study, participant's baseline fear appeared to predict future fear, regardless of further falls.

Fear-of-falling is significantly associated with previous falls and predictive of future falls and fear. RA patients would benefit from fall prevention measures whether or not they have previously fallen.

To our knowledge, only 1 study with limited sample size tried to evaluate the synergistic effects of ultrasound and low-level laser therapy (LLLT) in patients with knee osteoarthritis. Further research is needed to confirm this synergy with larger numbers and better design. Therefore, we will conduct this present randomized double-blind study to evaluate the synergistic effects of simultaneously applying ultrasound plus LLLT on pain and muscle function in patients with knee osteoarthritis. The study protocol is a randomized, controlled, double-blind design. The study will be conducted at our academic hospital from February 2021 to January 2022. The study protocol was approved through Institutional Review Board in the Hunan Provincial People's Hospital. Patients will be assigned at random to the ultrasound + LLLT group, LLLT group, or the ultrasound group. After baseline examination, all patients will be given a full explanation of the treatment protocol and will be required to sign a written informed consent for study participation and for publication of the results. All the data collectors, surgeons, statistical analysts, as well as result assessors are not aware of grouping assignment. The primary outcome is weekly change in pain intensity relative to baseline through 6 weeks of therapy. This protocol will provide a reliable theoretical basis for the following research. This study protocol was registered in Research Registry (researchregistry6470).

It is assumed that there will be a remarkable difference in postoperative outcomes between the intervention and control groups.

Rheumatoid arthritis (RA) causes substantial morbidity and mortality, and current treatments are suboptimal. Recent studies have demonstrated the short-term efficacy of minocycline in the treatment of patients with early RA. This study was undertaken to compare patients treated with conventional therapy in the early phase of their RA and those treated with minocycline, after 4 years of followup. Forty-six patients with seropositive RA of <1 year's duration had been enrolled in a double-blind study of minocycline (100 mg twice daily) versus placebo. After the blinded portion of the study (3-6 months, depending upon response), all patients were treated with conventional therapy. This report compares those patients randomized to receive placebo for 3 months and then conventional therapy for the duration of 4 years versus those originally randomized to receive minocycline. Twenty of the 23 original minocycline-treated patients and 18 of the 23 original placebo-treated patients were available for followup (mean 4 years). At followup, RA was in remission (American College of Rheumatology criteria) without disease-modifying antirheumatic drug (DMARD) or steroid therapy in 8 of the patients originally treated with minocycline compared with 1 patient in the placebo group (P = 0.02). Ten patients in the minocycline group versus 16 in the original placebo group currently require DMARD therapy (P = 0.02).

Among patients with seropositive RA, remissions are more frequent and the need for DMARD therapy is less in those treated early in the disease course with minocycline compared with those treated with conventional therapy delayed by an average of only 3 months. Minocycline appears to be an effective therapy for early RA; further investigation into its mechanism of action is needed.

Recent studies have suggested that the gut microbiota is altered in children with juvenile idiopathic arthritis (JIA). However, age, sex, and body mass index (BMI) were not matched in the previous studies, and the results are inconsistent. We conducted an age-, sex-, and BMI-matched cross-sectional study to characterize the gut microbiota in children with JIA, and evaluate its potential in clinical prediction. A total of 40 patients with JIA and 42 healthy controls, ranging from 1 to 16 years, were enrolled in this study. Fecal samples were collected for 16S rDNA sequencing. The data were analyzed using QIIME software and R packages. Specifically, the random forest model was used to identify biomarkers, and the receiver operating characteristic curve and the decision curve analysis were used to evaluate model performance. A total of 39 fecal samples from patients with JIA, and 42 fecal samples from healthy controls were sequenced successfully. The Chao 1 and Shannon-Wiener index in the JIA group were significantly lower than those in the control group, and the Bray-Curtis dissimilarity also differed significantly between the two groups. The relative abundance of 4 genera, Anaerostipes, Dialister, Lachnospira, and Roseburia, decreased significantly in the JIA group compared to those in the control group. The 4 genera included microbes that produce short-chain fatty acids (SCFAs) and were negatively correlated with some rheumatic indices. Moreover, 12 genera were identified as potential biomarkers by using the nested cross-validation function of the random forest. A random forest model constructed using these genera was able to differentiate the patients with JIA from the healthy controls, and the area under the receiver operating characteristic curve was 0.7975. The decision curve analysis indicated that the model had usefulness in clinical practice. The study is registered online at the Chinese Clinical Trial Registry on 11 May 2018 (registration number: ChiCTR1800016110).

The gut microbiota in patients with JIA is altered and characterized by a decreased abundance of 4 SCFA-producing genera. The decreases in the 4 genera correlated with more serious clinical indices. Twelve genera could be used as biomarkers and predictors in clinical practice.

Low-intensity pulsed ultrasound (LIPUS) has been known to promote bone healing by nonthermal effects. In recent studies, LIPUS has been shown to reduce inflammation in injured soft tissues. Xerostomia is one of the most common symptoms in Sjögren syndrome (SS). It is caused by a decrease in the quantity or quality of saliva. The successful treatment of xerostomia is still difficult to achieve and often unsatisfactory. The aim of this study is to clarify the therapeutic effects of LIPUS on xerostomia in SS. Human salivary gland acinar (NS-SV-AC) and ductal (NS-SV-DC) cells were cultured with or without tumor necrosis factor-α (TNF-α; 10 ng/ml) before LIPUS or sham exposure. The pulsed ultrasound signal was transmitted at a frequency of 1.5 MHz or 3 MHz with a spatial average intensity of 30 mW/cm(2) and a pulse rate of 20 %. Cell number, net fluid secretion rate, and expression of aquaporin 5 (AQP5) and TNF-α were subsequently analyzed. Inhibitory effects of LIPUS on the nuclear factor κB (NF-κB) pathway were determined by Western blot analysis. The effectiveness of LIPUS in recovering salivary secretion was also examined in a MRL/MpJ/lpr/lpr (MRL/lpr) mouse model of SS with autoimmune sialadenitis. TNF-α stimulation of NS-SV-AC and NS-SV-DC cells resulted in a significant decrease in cell number and net fluid secretion rate (p < 0.01), whereas LIPUS treatment abolished them (p < 0.05). The expression changes of AQP5 and TNF-α were also inhibited in LIPUS treatment by blocking the NF-κB pathway. Furthermore, we found that mRNA expression of A20, a negative feedback regulator, was significantly increased by LIPUS treatment after TNF-α or interleukin 1β stimulation (NS-SV-AC, p < 0.01; NS-SV-DC, p < 0.05). In vivo LIPUS exposure to MRL/lpr mice exhibited a significant increase in both salivary flow and AQP5 expression by reducing inflammation in salivary glands (p < 0.01).

These results suggest that LIPUS upregulates expression of AQP5 and inhibits TNF-α production. Thus, LIPUS may restore secretion by inflamed salivary glands. It may synergistically activate negative feedback of NF-κB signaling in response to inflammatory stimulation. Collectively, LIPUS might be a new strategic therapy for xerostomia in autoimmune sialadenitis with SS.

Rivaroxaban is the first licensed oral direct inhibitor of factor Xa. Recent studies from the RECORD trials suggest rivaroxaban has superior efficacy compared to enoxaparin in preventing venous thromboembolism (VTE) with no significant increase in the major bleeding risk. Concerns remain regarding the incidence of minor bleeding, consequent delayed wound healing and subsequent risk of infection. The aim of this observational study was to assess the incidence of post-operative complications in patients receiving either rivaroxaban or enoxaparin thromboprophylaxis following elective hip and knee arthroplasty. A total of 258 patients undergoing elective total hip or knee arthroplasty within one NHS Trust were included. A total of 202 subjects (mean age, 70.7 years ± 10.0, 43 % men) received a daily dose of 10 mg of oral rivaroxaban and 56 (mean age, 70.9 years ± 9.8, 39 % men) had a daily subcutaneous injection of 40 mg of enoxaparin as thromboprophylaxis. Endpoints included VTE (deep vein thrombosis and pulmonary embolism), haemorrhagic wound complications, hospital re-admission, requirement for blood transfusion, minor and major bleeding and death. There were no significant differences in the incidence of VTE, requirement for blood transfusion and readmission rate between rivaroxaban and enoxaparin-treated patients. The incidence of minor bleeding (2.0 vs. 0 %) and haemorrhagic wound complications (5.0 vs. 1.8 %) were non-significantly higher in the rivaroxaban-treated group. There were no cases of pulmonary embolism, major bleeding or death in either group.

Our experience with rivaroxaban in elective hip and knee arthroplasty showed no significant difference in the incidence of VTE or major bleeding. There was, however, a tendency to greater risk of minor bleeding and wound complications that were largely haemorrhagic in nature, which may have reached significance in a larger study.

Although CT scans are widely believed to provide the most accurate measurements of femoral anteversion, any estimate of the anteversion of the femur depends on the accuracy of the calculated axis of the femoral neck. We devised a method to measure the anteversion of the femur precisely using a 3D femoral computer model reconstructed from digitized femoral contours. Using this method, we compared the accuracy of three popular methods of anteversion measurement based on CT scans. The three popular CT methods were as follows: (a) the classic method of Weiner et al., based on a single CT image; (b) the method of Reikerås et al., in which the neck axis is defined by two superimposed images of the femoral head and neck; and (c) the method of Murphy et al., utilizing centroids of the head and the medullary canal. The accuracy of the single slice method was also examined using slices taken at four different neck slice levels within the proximal femur. CT scans of 30 femora were obtained using a helical CT scanner and reconstructed using custom software. Based on the 3D model, the true anteversion of the femora averaged 19.8 +/- 9.3 degrees (SD). Using the method of Weiner et al., the anteversion of the femora was underestimated by an average of 6.4 degrees (predicted value 13.4 +/- 10.4 degrees). Conversely, Murphy et al.'s method overestimated anteversion by an average of 6.3 degrees with an average value of 26.0 +/- 9.1 degrees. The difference between the true anteversion and the values predicted by both of these methods was statistically significant (p < 0.001). The average anteversion measured according to the method of Reikerås et al. was 17.8 +/- 8.9 degrees, 2.0 degrees less than the true anteversion of the sample (p < 0.005). Anteversion angles predicted from a slice just below the inferior edge of the head averaged 18.3 +/- 9.5 degrees, only 1.5-3.1 degrees less than the true anteversion of the femur (p = 0.14).

The single slice CT method has sufficient accuracy for use, provided the slice is taken just below the femoral head. In cases with a femoral head deformity or a valgus neck or where difficulty is encountered in positioning the patient, 3D reconstruction appears essential for accurate measurement of anteversion.

Joint replacement surgery is one of the most often performed routine procedures for the treatment of knee osteoarthritis in Germany. Currently, there is no consensus on indication criteria for total knee arthroplasty (TKA). The topic indication for TKA was processed using six guiding questions concerning: 1) Common practice in determining the indication for TKA; 2) Inclusion criteria in clinical trials; 3) Treatment goals/goal criteria; 4) Predictors for goal attainment; 5) Economic aspects of determining a TKA indication; 6) Guidelines of the "Working Group of Scientific Medical Societies" (AWMF) in other areas. The evidence mapping was conducted by systematically searching Medline via Ovid, the Cochrane Library, through hand searching national guidelines and selected journals as well as the AWMF guideline portal. 1) In Germany there is currently no consented guideline regarding indications for TKA surgery. 2) Indication criteria for clinical trials are: diagnosed osteoarthritis of the knee, limitations of age and BMI. The most common criteria for exclusion include rheumatoid/inflammatory arthritis, secondary diagnoses and allergies. 3) As yet, no international initiatives have been identified which, by involving all relevant stakeholders, have reached consensus regarding the indication criteria for TKA. 4) A variety of predictors were identified with effects on individual treatment goals acting in different directions. 5) Very few studies were identified concerning economic aspects of determining TKA indication. 6) Comparable AWMF guidelines are currently not available.

The findings of this study suggest that specific systematic reviews are needed to explore the following questions: What are the treatment goals of a TKA intervention? For whom are these relevant? And how are they measured? Continuous analyses are recommended in the field of predictors for a positive TKA outcome.

Osteoarthritis (OA) is a whole joint pathology involving cartilage, synovial membrane, meniscus, subchondral bone, and infrapatellar fat pad (IFP). Synovitis has been widely documented in OA suggesting its important role in pathogenesis. The aim of this study was to investigate the role of different joint tissues in promoting synovitis. Conditioned media (CM) from cartilage, synovial membrane, meniscus, and IFP were generated from tissues of five patients undergoing total knee replacement and used to stimulate a human fibroblast-like synoviocytes cell line (K4IM). Cytokines, chemokines, and metalloproteases release was analyzed in all CM by Bio-Plex Assay and sulfated glycosaminoglycan (GAG) content by dimethylmethylene blue assay. Gene expression of several markers was evaluated by real-time PCR in K4IM cells stimulated with the CM obtained from joint tissues. CM from all tissues produced high levels of IL-6, IL-8, and CCL2. CCL21, MMP-3, and -13 levels were detected in all CM except IFP. MMP-10 was present only in CM of cartilage and synovial tissues. IL-1β, IL-15, TNF-α, CCL5, and CCL19 were undetectable. However, only K4IM cells stimulated by the CM from OA synovium showed an increase of IL-6, CXCL-8, CCL21, MMP10, and IL-1β expression.

Our study showed that K4IM might be a suitable in vitro model for evaluating different cellular pathways in OA studies. Importantly, we demonstrated that in OA, all joint tissues might be involved in the progression of synovitis with a predominant role of synovial membrane itself compared to the other joint tissues.

Patients with myeloproliferative neoplasms (MPNs) experience a high persistence, prevalence, and severity of fatigue. There is currently only limited information regarding factors that contribute to fatigue in patients with MPNs. A 70-item, Internet-based survey regarding fatigue was developed by MPN investigators and patients/advocates and hosted by the Mayo Clinic Survey Research Center. Fatigue was found to be prevalent and severe among international survey respondents (1788 respondents). Higher body mass index (P<.001), current use of alcohol (P<.001), and current tobacco use (P = .0025) were found to be significantly associated with greater fatigue. Moderate/severe fatigue was present more frequently in those individuals who did not exercise compared with those who reported exercising at least once per week (P<.001). Medical comorbidities found to be significantly associated with greater fatigue included restless leg syndrome (P = .006), diabetes mellitus (P = .045), fibromyalgia (P < 0.001), chronic fatigue syndrome (P = .006), and chronic kidney disease (P = .02). Current use of antidepressants (P<.001), antihistamines (P = .0276), antianxiety medications (P = .0357), and prescription pain medications (P<.001) were found to be associated with worsened fatigue. Nearly 25% of respondents scored > 2 on the Patient Health Questionnaire, indicating a high probability of depression. Higher Brief Fatigue Inventory score, Myeloproliferative Neoplasm Total Symptom Score, and individual symptom items were all associated with a higher likelihood of depressive symptoms (P<.0001).

The management of fatigue should be multifactorial, with a comprehensive assessment and treatment plan to address all modifiable fatigue etiologies. Patients with MPNs likely have a higher prevalence of mood disturbances compared with the general population, suggesting the need to assess and intervene in this domain.

To examine genetic variations in the region surrounding loci of the major histocompatibility complex, and to investigate the probable location of a new candidate region on the short arm of chromosome 6 predisposing to primary Sjögren's syndrome (SS). We conducted an association study and positional candidate gene approach by microsatellite analysis. Five polymorphic microsatellite markers, D6S273, D6S439, D6S1645, D6S291, and DS61019, spanning the region 6p21.3, and establishing particular landmarks to discriminate between the human leukocyte antigen class II and tumor necrosis factor-a loci, were genotyped by polymerase chain reaction technique. A total of 64 patients with primary SS and 120 matched controls were examined. There was no genetic stratification among cases and controls. Genotype distribution analysis disclosed a significantly higher number of homozygotes for D6S439 locus in patients than in controls [odds ratio (OR): 3, 95% confidence interval (CI): 1.46-6.14, p = 0.004]. Confirmation of this homozygosity was established by the gene correlation intra-locus test (Fis value = +0.233, p = 0.0007). Allele D6S439*274 was associated to disease (OR: 3, 95% CI: 1.35-6.65, p = 0.006, pc = 0.04). Among patients, no significant linkage disequilibrium (LD) value was found between the studied microsatellites and TAP, HLA-DRB1, or HLA-DQB1 loci. In controls, there was LD between D6S1645 and D6S291 loci.

Our results indicate that D6S439 microsatellite defines a new susceptibility region for primary SS, independent of LD with TAP and HLA DQ/DR. These findings might imply that a gene surrounding this location is causally related to the disease.

The interface between pro-inflammatory cytokines and rheumatoid synovial fibroblast (sFLS) has central effects on rheumatoid arthritis (RA). The present study aimed to explore the role of IL-34 expression as one of major cytokine implicated in RA. We examined the expression of IL-34 after RA sFLS stimulated by IL-1β and TGF-β1 separately by reverse transcription polymerase chain reaction (RT-PCR). Transwell and wound closure techniques were used to detect whether IL-34 is involved in promoting cell migration. Cellular viability was determined via CCK-8 and cultural morphology assays between IL-34 downregulated group and non-transfected counterpart. We also tested the expression of VEGF gene with RT-PCR analysis and activation of the major signalling pathways by western blot in IL-34 down-regulated group, IL-1β or TGF-β1 treated groups. Propidium iodide (PI) staining and fluoresceine isothiocyanate (FITC) Annexin V and propidium iodide apoptosis assay were used to analyse cell cycle arrest and apoptosis separately in IL-34 down-regulated cells. We found that IL-1β significantly enhanced IL-34 expression, while contrarily, TGF-β1 restrained IL-34 gene expression. Transwell and wound closure techniques showed that IL-34 was involved considerably in promoting cell migration. However, IL-34 knock-down restricted sFLS migration possibly through the diminishing of MMP2 and MMP9 expression. Interestingly, IL-34 down-regulated cells exhibited significantly low cellular viability compared with the non-transfected counterpart via CCK-8 and cultural morphology assays. We found that IL-34 down-regulated cells have low VEGF gene expression compared with treated cells. PI staining showed a G0/G1 cell cycle arrest in IL-34 down-regulated cells. FITC Annexin V and propidium iodide apoptosis assay verified that IL-34 down-regulated cells induced massive apoptosis through apoptotic signalling caspase3, while IL-1β treated cells presented termination of cellular apoptosis signalled by BCL-2. Furthermore, we observed IL-34 induced activation of ERK1/2 and AKT pathways while IL-34 down-regulation significantly decreased the activation of these pathways.

Our data add novel insights into the pathogenesis of RA and we suggest that IL-34 plays a dominant role in controlling migration and proliferation of sFLS. Consequently, therapeutic strategies targeting IL-34 could be a potent therapy for RA.

Biologic agents may induce immune responses that could impact drug action. The aims of this study were to assess antidrug antibodies (ADAs) in patients with rheumatoid arthritis (RA) from Argentina treated with etanercept, adalimumab, or infliximab at a single visit and correlate it with efficacy outcomes. In this subset analysis of a noninterventional, multinational, cross-sectional study (NCT01981473), adult patients with RA treated continuously for 6 to 24 months with etanercept, adalimumab, or infliximab were evaluated for ADAs and trough drug concentrations of 2 days or less prior to the next scheduled dose. Efficacy measurements included Disease Activity Score based on a 28-joint count-erythrocyte sedimentation rate, low disease activity, and Health Assessment Questionnaire-Disability Index. Targeted medical history of injection site/infusion reactions, serum sickness, and thromboembolic events were reported. Baseline demographics, disease characteristics, and duration of treatment of the 119 patients (etanercept: n = 54, adalimumab: n = 52, infliximab: n = 13) were similar across all groups. No etanercept-treated patient tested positive for ADAs compared with 19 (36.5%) of 52 patients and 4 (30.8%) of 13 patients treated with adalimumab and infliximab, respectively. In adalimumab- and infliximab-treated patients, ADA presence correlated negatively with trough drug levels. A greater proportion of ADA-negative patients achieved Health Assessment Questionnaire-Disability Index of 0.5 or less and had better composite efficacy measures compared with ADA-positive patients. The rate of targeted medical events reported was low.

In this subset analysis, RA patients from Argentina treated with adalimumab or infliximab, but not etanercept, tested positive for ADAs. Antidrug antibody-negative patients showed a tendency toward better clinical outcomes compared with ADA-positive patients.

The purpose of this study was to estimate the excess burden of RA in Ontario, the largest province in Canada. The records of all adult Ontarians who participated in the Canadian Community Health Survey (CCHS) cycle 1.1 (2000/2001) and provided consent to data linkage were linked to the Ontario Health Insurance Program (OHIP) physician claims database and the Discharge Abstract Database (DAD) In-Patient (i.e. hospitalisation) and Day-Procedure databases. RA individuals (n=233) were identified using CCHS 1.1 and the physician claims database. A control group matched by age, gender and rural/urban status was created with three controls for one case (n=699). Socio-demographic variables, medical characteristics, health-related quality of life (HRQoL) and one-year physician services, hospitalizations and day procedures costs were determined for the RA and non-RA groups. Regression techniques were used to identify predictors of medical characteristics, utility and cost data. The mean age of the population was 59 years and 76% were female. Compared to the matched control group, individuals with RA were statistically more likely to be obese, less educated, physically inactive and have a lower income. RA individuals also reported a statistically higher number of comorbidities and a lower HRQoL. Although no statistical differences were observed between the RA and non-RA groups for the costs associated with hospitalisations, the physician ($1,015 vs. $624, respectively) and day procedure ($102 vs. $51, respectively) costs were statistically higher among RA individuals.

These results indicate that the human and economic burden of RA in Ontario is considerable.

Osteoarthritis (OA) is the most common joint pathology and the main cause of disability in elderly persons. Arthroplasty still remains the most effective treatment of OA. Routine post-operative patient assessment does not include an objective functional examination leading to conclusions regarding the need of further rehabilitation. This role is played by gait analysis performed in patients after arthroplasty. The aim of the study was to conduct a quantitative and qualitative analysis of selected gait parameters in patients after unilateral cementless hip arthroplasty. The study involved a group of 16 patients who were examined before and after hip arthroplasty. Gait analysis was conducted before surgery and at least 6 months after the procedure. The Smart DX BTS system for spatial gait analysis was used. The duration of the stance phase on the affected side was 63.8 [% gait cycle] and was significantly shorter (p<0.05) than the phase on the unaffected side, with a duration of 69.4 [% gait cycle]. After surgery, the duration of swing phase on the unaffected side increased (p<0.05) from 30.6 to 35.1 [% gait cycle]. A statistically significant change was also found in the double support phase (the arthrotic limb as the front limb), which was markedly shortened. The average length of a single and double step, cadence, average gait velocity, and the velocity of leg swing in the swing phase increased. The range of hip mobility increased in all planes, especially in the sagittal plane.

The space and time gait parameters with regard to the operated leg after hip arthroplasty indicate an improvement as compared with the baseline results; however, they do not reach the values found in healthy persons.

To evaluate the validity of using the conventional anteroposterior (AP) radiograph of the knee in order to identify joint space narrowing (JSN) at an early stage of osteoarthritis (OA). Grading of JSN using a 0-5 score and quantitative measurement of joint space width (JSW) of the medial and lateral compartments of the tibiofemoral joint in AP and fluoroscopically assisted posteroanterior Lyon schuss (LS) radiographs of 202 patients with knee OA. Knees without definite JSN (score <2) were twice as common in AP than in LS radiographs (36.1% vs 18.8%). The number of knees showing definite medial JSN was identical in both views but four knees showing a medial OA in AP view were classified differently in the LS radiographs (three bicompartmental OA and one lateral OA). The frequency of lateral JSN was approximately twice as great in the LS view as in the AP view. JSN score was significantly higher (p<0.001) and JSW was significantly smaller (p<0.01) in the LS view than in the AP view. In knees with definite JSN, JSW of the compartment with no narrowing was significantly (p<0.04) larger than in knees that did not exhibit definite JSN. Medial JSW and lateral JSW were inversely correlated (p<0.001).

The standing AP radiograph performed poorly in identifying both the location of JSN in patients with early tibiofemoral OA (especially, lateral OA) and the severity of JSN. The LS radiographs are preferable to standing AP views for the selection of patients for therapeutic trials of structure-modifying OA drugs.

ABT-494 is a potent and selective Janus kinase (JAK) 1 inhibitor being developed for the treatment of several autoimmune disorders, with potential for an improved safety profile compared with non-selective JAK inhibitors. This work characterized the pharmacokinetics, safety, and tolerability of ABT-494 following single and multiple dosing of the immediate-release formulation. ABT-494 single (1-48 mg or placebo; n = 56) and multiple (3-24 mg or placebo twice daily for 14 days; n = 44) doses in healthy subjects, as well as multiple doses (3-24 mg or placebo twice daily for 27 days; n = 14) in subjects with rheumatoid arthritis (RA) on a background of methotrexate were evaluated. Pharmacokinetic samples were collected and safety and tolerability were assessed. ABT-494 followed bi-exponential disposition, with a terminal elimination half-life of 6-16 h and a functional half-life, calculated from maximum observed plasma concentration (C ClinicalTrials.gov ( https://clinicaltrials.gov/ ) identifier: NCT01741493.

The favorable pharmacokinetics, safety, and tolerability results from these studies supported further evaluations of ABT-494 in phase IIb dose-ranging trials in RA and Crohn's disease.

Extensive blood loss after total knee arthroplasty (TKA) may be a potential problem since it leads to anaemia, increased need for transfusion and prolonged hospitalization. Aim of this study was to investigate the effects of postoperative knee flexion after TKA on blood loss and the need for transfusion. One hundred consecutive patients undergoing primary TKA from 2012 to 2013 were randomizely divided into two groups. In one group, the knee was extended for the first 6 h after surgery, whereas in the other was flexed at 90° for the same time. Two doses of endovenous tranexamic acid were administered in all subjects. Patients were homogeneous for all the possible confounding factors. Calculated blood loss was 846 ± 197 (ml) in the flexion group and 1,242 ± 228 (ml) in the extension group (p < 0.05). Drop of haemoglobin levels at 24 h in the study group and the control group was 1.9 ± 0.8 (g/dl) and 3.0 ± 0.5 (g/dl), respectively (p < 0.01). Drop of haematocrit at 24 h was 4.5 ± 0.2 (%) in the flexion group and 6.7 ± 0.3 (%) in the extension group (p < 0.05). Blood transfusion was necessary in 5 patients in the control group and was not necessary in any patient of the study group. Average knee flexion at day 7 was 105° ± 4° in the flexion group and 98° ± 7° in the extension group.

Knee flexion at 90° after TKA, associated with the intraoperative use of tranexamic, acid is an effective method to reduce blood loss and the need for blood transfusion. The routine use of the present protocol is effective in reducing social costs and length of hospitalization of TKA procedures.

To investigate the relation of coping strategies to coping effectiveness, helplessness, and mental as well as physical well-being as indicators of quality of life. Cross-sectional international study. Coping strategies were assessed by a validated 18-item questionnaire, while coping effectiveness and helplessness were measured by numerical rating scales. The predictability of both and quality of life (SF-36) was evaluated by multiple linear regression including demographic and disease-related factors. Four hundred thirty-four rheumatoid arthritis (RA) patients (77% female; mean age 55.96 ± 13.34 years) were included. Distancing was the coping strategy used most frequently in RA patients (mean ± SD 1.89 ± 0.78 on a scale ranging from 0 to 3). Female RA patients used coping strategies significantly more often than males, whereas age and duration of disease did not seem to influence the use of coping strategies. Cognitive reframing and active problem-solving contributed to coping effectiveness while emotional expression was related to helplessness. Coping effectiveness was positively related to general health perception, suggesting certain coping strategies to be effective in influencing the quality of life of RA patients.

Coping strategies used in RA are dependent on gender, but not on age. The use of problem-focused coping strategies may allow for an improved coping effectiveness in patients with RA, while also influencing mental and physical well-being as indicators of quality of life. Coping should therefore be considered as an important factor in determining the overall health state of patients with RA.

Intraarticular injections of sodium hyaluronate (Na-HA) appear effective in reducing subjective symptoms of osteoarthritis (OA) and may also have protective effects on the cartilage matrix. The present study analyzed the suppressive effects of Na-HA on the release and degradation of aggrecan and on levels of nitric oxide (NO) in the joint fluid of patients with knee OA. Sixteen OA patients with knee joint effusion were treated by 5 weekly intraarticular injections of Na-HA. Prior to each Na-HA injection, joint fluid was collected to determine the levels of chondroitin 4-sulfate (C4S) and chondroitin 6-sulfate (C6S), intact aggrecan and NO. One week after the final injection, the joint fluid levels of C4S, C6S, and NO were significantly decreased. In contrast, the joint fluid level of intact aggrecan was stable during the series of Na-HA injections. A trend was seen for a positive correlation (P < 0.1) between the clinical score and C4S or C6S joint fluid levels, and for a negative correlation between the joint fluid levels of intact aggrecan and C4S or C6S. No significant correlations were observed between joint fluid levels of NO, the clinical score, and levels of C4S, C6S, and intact aggrecan.

The results of this study suggest that intraarticularly injected Na-HA is able to improve the clinical symptoms of OA partially based on its ability to reduce the release and degradation of aggrecan and/or to enhance the synthesis of aggrecan in the joint tissues of the patients with knee OA. While Na-HA also reduces the NO level in the joint fluid of patients with knee OA, this effect may be independent from the other effects of Na-HA.

To compare the benefits of a tight-control/treat-to-target strategy (TC/T2T) in axial spondyloarthritis (axSpA) with those of usual care (UC). Pragmatic, prospective, cluster-randomised, controlled, open, 1-year trial (NCT03043846). 18 centres were randomised (1:1). Patients met Axial Spondylo Arthritis International Society (ASAS) criteria for axSpA, had an Ankylosing Spondylitis Disease Activity Score (ASDAS) ≥2.1, received non-optimal treatment by non-steroidal anti-inflammatory drugs and were biologic-naive. (1) Percentage of patients with a ≥30% improvement on the ASAS-Health Index (ASAS-HI). Other efficacy outcomes and adverse events were recorded. A health economic evaluation was performed. Two-level mixed models were used to estimate efficacy outcomes. Cost-effectiveness was assessed by the incremental cost per quality-adjusted life-year (QALY) gained for TC/T2T versus UC. 160 patients were included (80/group). Mean (SD) age was 37.9 (11.0) years and disease duration was 3.7 (6.2) years; 51.2% were men. ASDAS at inclusion was 3.0 (0.7), and ASAS-HI was 8.6 (3.7). ASAS-HI improved by ≥30% in 47.3% of the TC/T2T arm and in 36.1% of those receiving UC (non-significant). All secondary efficacy outcomes were more frequent in the TC/T2T arm, although not all statistically significant. Safety was similar in both arms. From a societal perspective, TC/T2T resulted in an additional 0.04 QALY, and saved €472 compared with UC. NCT03043846.

TC/T2T was not significantly superior to UC for the primary outcome, while many secondary efficacy outcomes favoured it, had a similar safety profile and was favourable from a societal health economic perspective.

To test the effect of infusions of CAMPATH-1H on levels of proinflammatory secretory phospholipase A2 (sPLA2) and tumor necrosis factor alpha (TNF-alpha) in patients with rheumatoid arthritis (RA). Two patients with RA were infused with CAMPATH-1H; extracellular nonpancreatic sPLA2 activity was tested using radiolabelled E. coli membrane phospholipid, and circulating TNF-alpha levels were tested by ultrasensitive immunoassay. Circulating TNF-alpha began to rise within the first 2 h after infusion, reaching > 1000-fold values compared to preinfusion levels. Circulating sPLA2 activity began to rise a few hours after the start of infusion and reached extremely high values in 12 h, concomitant with fever and hypotension. The activity of sPLA2 decreased to pretreatment values in 3-18 days after infusion.

The mechanism leading to the increase of TNF-alpha and hyperphospholipasemia A2 has not been elucidated. It is possible that CAMPATH-1H activates cells that synthesize and release TNF-alpha and sPLA2, and/or that it induces interleukin 2 release, which in turn activates TNF-alpha, with subsequent release of sPLA2.

To determine the immunophenotypic profiles of circulating lymphocytes in patients with different disease types of Juvenile Idiopathic Arthritis (JIA). Peripheral blood lymphocyte subsets from 19 patients with oligoarticular JIA (o-JIA), 10 patients with polyarticular JIA (p-JIA), 12 patients with systemic JIA (s-JlA) andfrom 41 age-matched healthy controls were characterized by two color immunofluorescence flow cytometry analysis. Patients with o-JIA and p-JIA had increased numbers of HLA-DR+ Tcells and Tcells co-expressing CD57 and CD16/56, indicating T cell activation and terminal differentiation of CD8+ T cells respectively. By contrast, in patients with s-JIA there was no increase in the activation or differentiation markers on T cells, but a profound decrease in circulating NK cells. All patients had hypergammaglobulinemia consistent with B cell hyperactivity, but increased numbers of CD5+ B cells were found only in o-JIA and p-JIA.

Distinct immunophenotypic lymphocyte profiles in patients with o-JIA and p-JIA compared to patients with s-JIA as demonstrated in this study, are consistent with afundamental heterogeneity of the disease.

To assess whether Sjogren's Syndrome (SS) is associated with outcomes after total knee or hip arthroplasty (TKA/THA). We used the 1998-2014 U.S. National Inpatient Sample data. We performed multivariable-adjusted logistic regression analyses to assess the association of SS with healthcare utilization (hospital charges, length of hospital stay, discharge to non-home setting), and in-hospital complications (implant infection, revision, transfusion, mortality), controlling for important covariates and confounders. In sensitivity analyses, we additionally adjusted the main models for hospital location/teaching status, bed size, and region. We examined 4,116,485 primary THAs and 8,127,282 primary TKAs performed from 1998 to 2014; 12,772 (0.2%) primary TKAs and 6222 (0.2%) primary THAs were done in people with SS. In multivariable-adjusted models, SS was associated with a statistically significant higher odds ratio (OR; 95% confidence interval (CI)) of discharge to a rehabilitation/inpatient facility post-THA, 1.13 (1.00, 1.28), but not post-TKA, 0.93 (0.86, 1.02). We noted no differences in the length of hospital stay or hospital charges. SS was associated with significantly higher adjusted odds of in-hospital transfusion post-THA, 1.37 (1.22, 1.55) and post-TKA, 1.21 (1.10, 1.34). No significant differences by SS diagnosis were seen in hospital stay, hospital charges implant infection, implant revision or mortality rates.

People with SS had higher transfusion rate post-TKA/THA, and higher rate of discharge to non-home setting post-THA. The lack of association of SS with post-arthroplasty complications should reassure patients, surgeons and policy-makers about the utility of TKA/THA in people with SS undergoing these procedures.

Tumor necrosis factor-α (TNFα) has received significant attention as a mediator of lumbar radiculopathy, with interest in TNF antagonism to treat radiculopathy. Prior studies have demonstrated that TNF antagonists can attenuate heightened nociception resulting from lumbar radiculopathy in the preclinical model. Less is known about the potential impact of TNF antagonism on gait compensations, despite being of clinical relevance. In this study, we expand on previous descriptions of gait compensations resulting from lumbar radiculopathy in the rat and describe the ability of local TNF antagonism to prevent the development of gait compensations, altered weight bearing, and heightened nociception. Eighteen male Sprague-Dawley rats were investigated for mechanical sensitivity, weight-bearing, and gait pre- and post-operatively. For surgery, tail nucleus pulposus (NP) tissue was collected and the right L5 dorsal root ganglion (DRG) was exposed (Day 0). In sham animals, NP tissue was discarded (n = 6); for experimental animals, autologous NP was placed on the DRG with or without 20 μg of soluble TNF receptor type II (sTNFRII, n = 6 per group). Spatiotemporal gait characteristics (open arena) and mechanical sensitivity (von Frey filaments) were assessed on post-operative Day 5; gait dynamics (force plate arena) and weight-bearing (incapacitance meter) were assessed on post-operative Day 6. High-speed gait characterization revealed animals with NP alone had a 5% decrease in stance time on their affected limbs on Day 5 (P ≤0.032). Ground reaction force analysis on Day 6 aligned with temporal changes observed on Day 5, with vertical impulse reduced in the affected limb of animals with NP alone (area under the vertical force-time curve, P <0.02). Concordant with gait, animals with NP alone also had some evidence of affected limb mechanical allodynia on Day 5 (P = 0.08) and reduced weight-bearing on the affected limb on Day 6 (P <0.05). Delivery of sTNFRII at the time of NP placement ameliorated signs of mechanical hypersensitivity, imbalanced weight distribution, and gait compensations (P <0.1).

Our data indicate gait characterization has value for describing early limb dysfunctions in pre-clinical models of lumbar radiculopathy. Furthermore, TNF antagonism prevented the development of gait compensations subsequent to lumbar radiculopathy in our model.

The aim of this study was to investigate the effects of andrographolide on matrix metalloproteinases (MMP) 1, 3, and 13 and inducible nitric oxide synthase (iNOS) in human articular chondrocytes from osteoarthritic cartilage. Passaged chondrocytes were pretreated with or without andrographolide for 2 h, followed by coincubation with interleukin-1 beta (IL-1β) 1 ng/ml for 24 h. Expression levels of MMP-1, 3, and 13, tissue inhibitor of metalloproteinase-1 (TIMP-1), and iNOS were evaluated using real-time-quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, and Western blotting. Nitric oxide (NO) was analyzed using the Griess reaction assay. Involvement of nuclear factor kappa B (NF-κB) was assessed by Western blotting, transient transfection, and luciferase reporter assay. Andrographolide tested in these in vitro studies was found be an effective antiarthritic agent, as evidenced by potent inhibition of MMP-1, 3, and 13 and iNOS expression, as well as upregulation of TIMP-1 in IL-1β-stimulated human articular chondrocytes (p < 0.05). The mechanism of andrographolide's inhibitory effects was mediated by attenuating the activation of NF-κB in human chondrocytes in the presence of IL-1β.

Andrographolide was a potent inhibitor of the production of inflammatory and catabolic mediators by chondrocytes, suggesting that this natural compound may merit consideration as a therapeutic agent for treating and preventing osteoarthritis.

Early and accurate risk prediction of walking limitations after total knee arthroplasty (TKA) is important for clinical and economic reasons. However, to our knowledge, no studies have systematically integrated multiple predictors into a single, clinically practical model. Our study aimed to develop a prediction model to estimate the risk of post-TKA walking limitations. We performed a prospective cohort study of 1096 patients who underwent elective, primary TKA between July 2013 and September 2014. Candidate predictors included patient demographics, surgical factors, and pre- and early (1-mo) post-TKA functional measures. The outcome of interest was self-reported walking limitations at 6 months of post-TKA. We used multivariable proportional odds regression with bootstrap internal validation to develop the model. In all, 12% of patients reported walking limitations (maximum walk time ≤ 15 min) at 6 months postsurgery. The main predictors of increasing levels of walking limitations were preoperative walking limitations (overall p < 0.001), higher levels of body mass index [interquartile range (IQR)-OR 1.3, 95% CI 1.2-1.5], lower values of 1-month post-TKA gait speed (IQR-OR 1.9, 95% CI 1.3-2.6), the presence of contralateral knee pain (OR 1.9, 95% CI 1.2-3.0), and the use of a quadstick preoperatively (OR 3.5, 95% CI 1.7-7.3). The prediction model had an optimism-corrected concordance index of 0.71.

A small but sizable proportion of patients with TKA had persistent mobility limitations. Our prediction model may help to risk-stratify patients, and external validation is required before the model can be used in clinical practice.

To describe an enthesitis-related arthritis (ERA) inception cohort and determine which entheses and joints are most commonly affected. We reviewed a retrospective inception cohort study of children with ERA who were diagnosed and treated at The Children's Hospital of Philadelphia between November 2007 and December 2009. During the study period, there were 32 newly diagnosed ERA patients. Fifty-nine percent were male, and the median age at the date of initial evaluation was 12.5 years (interquartile range [IQR] 10.2-14.3 years). The median number of tender entheses at presentation was 2 (IQR 0-5), and 21 subjects (66%) had at least 1 tender enthesis. The most prevalent tender entheses were the patellar ligament insertion at the inferior pole of the patella, the plantar fascial insertion at the calcaneus, the Achilles tendon insertion at the calcaneus, and the plantar fascial insertion at the metatarsal heads. Enthesitis was most often symmetric. The median number of active joints was 2 (IQR 0-4). The most commonly affected joints were the sacroiliacs, knees, and ankles. Sacroiliitis, which was defined clinically, was most often symmetric, while peripheral arthritis was most frequently asymmetric. The odds of having active enthesitis at 6 months increased significantly with each additional tender enthesis at the initial evaluation.

Among pediatric patients with ERA, lower extremity enthesitis is prevalent at the time of diagnosis and is likely to persist 6 months later. Future studies should address standardization of the enthesitis examination, the pattern of enthesitis over time, enthesitis response to therapy, and the impact of enthesitis on quality of life.

Minocycline-induced cutaneous pigmentation is an adverse effect that may be more common than is generally realized. It is usually reported in patients undergoing chronic minocycline therapy for acne vulgaris. The case of a 69-year-old woman taking minocycline for rheumatoid arthritis is presented, and its differential diagnosis discussed in order to characterize the clinical features of minocycline-induced cutaneous pigmentation.

Patients undergoing minocycline therapy for rheumatoid arthritis may develop bluish-grey pigmentation over the legs and forearms. Cutaneous pigmentation is a well recognized adverse effect of minocycline therapy that is usually reported in young patients on chronic therapy for acne vulgaris. However, the antiinflammatory properties of minocycline have also made it useful in the management of various inflammatory conditions such as rheumatoid arthritis.1 We report the case of a 69-year-old woman who developed progressive cutaneous pigmentation, affecting mainly the legs, approximately 3 months after beginning minocycline therapy for rheumatoid arthritis.

Hyperuricaemia and gout are well-recognized complications of diuretic use. The aim of this study was to examine the clinical and genetic features of diuretic-associated gout. Participants (n = 1365) fulfilling the 1977 ARA gout classification criteria, recruited from primary and secondary care, attended a study visit that included a detailed clinical assessment. Use of diuretic therapy was recorded during the study visit, and was confirmed by electronic dispensing data [n = 426 (31.2%) on diuretics]. Gout-associated single nucleotide polymorphisms were genotyped. Clinical and genetic features of diuretic-associated gout were analysed using a case-control study design (diuretics vs no diuretics). In the diuretic group there were more women, higher rates of comorbid conditions, higher BMI and lower estimated glomerular filtration rate compared with those not taking diuretics. Gout disease duration, frequency of gout flares and presence of tophi were similar in the two groups. Patients on diuretics had higher age of gout presentation and higher recorded serum urate. The ABCG2 rs2231142 risk allele was present less frequently in the diuretic group (36.1%) compared with those not on diuretics (47.6%, P = 1.2 × 10(-4)). The differences in ABCG2 were observed in both men and women with gout.

Diuretic-associated gout represents a medically complex condition. Although age of gout onset is later and serum urate concentrations are higher in those on diuretics, other clinical features of gout are similar. The observed differences in the ABCG2 risk allele frequency suggest that some genetic factors play a less dominant role in diuretic-associated gout compared with primary gout.

Guselkumab, a human monoclonal antibody specific to interleukin-23p19, demonstrated efficacy and safety versus placebo through week 24 of the phase III DISCOVER-2 trial in biologic-naive patients with psoriatic arthritis (PsA). Here we report 1-year DISCOVER-2 findings. Adults with active PsA (≥5 swollen and ≥5 tender joints; C-reactive protein level ≥0.6 mg/dl) despite standard nonbiologic treatment were randomized to receive subcutaneous injections of guselkumab 100 mg every 4 weeks, guselkumab 100 mg at week 0, week 4 and every 8 weeks thereafter, or placebo with crossover to guselkumab 100 mg every 4 weeks at week 24. We primarily evaluated clinical efficacy through week 52 by imputing missing data (nonresponse for categorical end points; no change/using multiple imputation for continuous end points). Observed radiographic scores and adverse events (AEs) were summarized. Of 739 randomized, treated patients, 93% completed week 52. The proportions of patients in whom a ≥20% improvement from baseline in American College of Rheumatology criteria (ACR20) was achieved were maintained after week 24, reaching 71% (173 of 245) and 75% (185 of 248) for patients randomized to receive treatment every 4 weeks or every 8 weeks, respectively, by week 52. The proportions of patients in whom ACR50/ACR70 and skin responses, minimal or very low disease activity, and dactylitis or enthesitis resolution were achieved at week 24 were also maintained through week 52. Further, low levels of radiographic progression, along with improvements in physical function and health-related quality of life, were sustained through week 52 with continued guselkumab treatment. Few patients experienced serious infections through week 52, with no evidence of a dosing regimen response or increase from weeks 0-24 (4 of 493 [0.8%]) to weeks 24-52 (3 of 493 [0.6%]) among guselkumab-randomized patients. No patient developed an opportunistic infection or died.

In biologic-naive PsA patients, guselkumab provided sustained improvements across diverse manifestations and maintained a favorable risk-benefit profile through week 52.

Subclinical joint inflammation in patients with arthralgia is predictive for progression to rheumatoid arthritis (RA). However, the time course of progression for bone marrow edema (osteitis), synovitis, and/or tenosynovitis is unsettled. This longitudinal study assessed the course of magnetic resonance imaging (MRI)-detected subclinical joint inflammation during progression to RA. Patients that progressed from clinically suspect arthralgia (CSA) to RA underwent 1.5-T MRI of the metacarpophalangeal (MCP), wrist, and metatarsophalangeal (MTP) joints at presentation with arthralgia and at first identification of synovitis assessed through physical examination (n = 31). MRIs were evaluated for osteitis, synovitis, tenosynovitis, and erosions by two readers, blinded for clinical data and order in time. To estimate changes in MRI scores between the asymptomatic state and CSA onset, scores of MRI features at CSA baseline were compared with scores from age-matched symptom-free persons. At presentation with CSA, synovitis and tenosynovitis scores were higher than scores from age-matched symptom-free persons (p = 0.004 and p = 0.001, respectively). Anti-citrullinated protein antibody (ACPA)-positive arthralgia patients also had increased osteitis scores (p = 0.04). Median duration between presentation with arthralgia and RA development was 17 weeks. During progression to RA, synovitis and osteitis increased significantly (p = 0.001 and p = 0.036, respectively) in contrast to tenosynovitis and erosion scores. This pattern was similar in both ACPA subsets, although statistical significance was reached for synovitis and osteitis in ACPA-negative but not ACPA-positive RA.

Increased tenosynovitis and synovitis scores at CSA onset and the increase in synovitis and osteitis during progression to RA suggest an 'outside-in' temporal relationship of arthritis development, in particular for ACPA-negative RA. For ACPA-positive RA, further studies are needed.

To determine if mixed connective tissue disease (MCTD) can be considered an independent clinical entity, to compare 3 different classification criteria for MCTD (Kasukawa, Alarcón-Segovia, and Sharp), and to define predictors (clinical features and autoantibodies) of potential evolution toward other connective tissue diseases (CTDs). One hundred sixty-one MCTD patients were evaluated retrospectively at the diagnosis and in 2008. They were classified, at the diagnosis, according to the 3 classification criteria of MCTD (Sharp, Alarcón-Segovia, and Kasukawa) and reclassified in 2008 according to their evolution. Statistical analyses were performed to find out predictors (clinical features and autoantibodies) of evolution into other CTDs. After a mean of 7.9 years of disease, 57.9% of patients still satisfied MCTD classification criteria of Kasukawa; 17.3% evolved into systemic sclerosis, 9.1% into systemic lupus erythematosus, 2.5% into rheumatoid arthritis, 11.5% was reclassified as affected by undifferentiated connective tissue disease, and 1.7% as suffering from overlap syndrome. Kasukawa's criteria were more sensitive (75%) in comparison to those of Alarcón-Segovia (73%) and Sharp (42%). The presence of anti-DNA antibodies (P = 0.012) was associated with evolution into systemic lupus erythematosus; hypomotility or dilation of esophagus (P < 0.001); and sclerodactyly (P = 0.034) with evolution into systemic sclerosis.

MCTD is a distinct clinical entity but it is evident that a subgroup of patients may evolve into another CTD during disease progression. Initial clinical features and autoantibodies can be useful to predict disease evolution.

To determine the distribution of clinically palpable hand interphalangeal (IP) nodes at each finger and thumb joint in a population with nodes, the influence of left or right hand dominance and sex on the development of nodes, and the association between nodes and underlying radiographic features of osteoarthritis (OA). We performed a cross-sectional analysis of participants in the Genetics of Osteoarthritis and Lifestyle (GOAL) study who had ≥1 Heberden's nodes or Bouchard's nodes on clinical examination. Frequencies (%) of nodes were described for each IP joint in the hand. Associations between nodes and underlying radiographic OA were shown with odds ratios (ORs) and 95% confidence intervals. A logistic regression model was used to adjust for the following confounding factors: age, sex, body mass index, left or right hand dominance, hand trauma, occupation with heavy manual activity, and participation in sports. Of the 3,170 GOAL participants, 1,939 had ≥1 nodes (mean age 68 years, 54% women). The distal IP joints of the index finger were the most frequently affected, followed by the thumb IP joint. Nodes were more common in dominant hands and women. There was a significant association between nodes and underlying radiographic OA (OR range 2.26-21.23). This association was stronger for joint space narrowing than for osteophytes. A dose-response relationship was found between clinical severity of Heberden's nodes and underlying radiographic change.

Our study supports the positive association between nodes and radiographic OA, especially narrowing, and the influence of sex and left or right hand dominance on development of nodes. In this age group, presence of nodes may be taken as an indication of underlying small joint OA.

Numerous methods for isolation of human chondrocytes are reported in the literature, most based on isolation from animal cartilage. Normal human articular cartilage (NHAC) poses particular problems for isolating chondrocytes when compared to animal or other types of human cartilage: a hardy matrix, combined with few and friable chondrocytes makes isolation difficult. Our objective was to develop an efficient method of isolating chondrocytes from NHAC without jeopardising the viability of these cells. In this study we demonstrate that lowering the enzymatic digestion temperature to 27 degrees C increases cell yield and chondrocyte viability. We then optimised this low temperature isolation of chondrocytes from NHAC by comparing the relative efficacies of trypsin and protease and hyaluronidase in combination with different types of collagenase (I, II and XI) at releasing chondrocytes from their surrounding cartilaginous matrix. Enzymes were tested at different concentrations and for differing times. Outcome measures included determining the amount of cartilage digested, the number of viable chondrocytes isolated per gram of cartilage and cell adherence rates.

From these set of experiments, the method that maximised cell yield without jeopardising cell viability proved to be a two stage process: pre-digestion step using trypsin for 15 min; followed by overnight digestion with a combination of two types of collagenase (types I and II) and at a lower temperature of 27 degrees C. This has resulted in an efficient and robust method of releasing chondrocytes from cartilage, without jeopardising the viability of these cells.

Patellofemoral osteoarthritis is a common presentation in the outpatients' physical therapy clinics. The muscle imbalance between the vastus medialis oblique and vastus lateralis muscles is one of the main factors that lead to the development of this condition. To compare the effect of a squatting versus squatting with hip adduction in management of patellofemoral osteoarthritis. Patients in group A received a traditional physical therapy program in addition to squatting exercise and those in group B received a traditional physical therapy program in addition to squatting with hip adduction exercise for four weeks. The primary outcome measures were pain on the numerical rating scale (NRS) and performance of functional activities by Kujala scale, while the secondary outcomes were vastus medialis oblique (VMO) and vastus lateralis (VL) amplitudes as well as the VMO:VL ratio by surface electromyography were considered before and after intervention. Thirty patients (group A n= 15; group B n= 15) were randomized and analyzed. Comparing both groups post-program revealed that there was no significant difference between both groups regarding the vastus medialis oblique activity, VMO:VL ratio, pain intensity and performance of functional activities.

Both a traditional physical therapy program in addition to squatting exercise and a traditional physical therapy program in addition to squatting exercise with hip adduction are effective in reduction of pain intensity increases performance of functional activities, and vastus medialis oblique amplitude. However, there is no superiority of one program over the other.

Inappropriately high levels of expression of HLA-DR molecules or their expression on inappropriate cells, e.g. synovial tissue and T cells, may result in an aberrant tissue-destructive immune response and thus cause susceptibility to rheumatoid arthritis (RA). Patients and controls were typed for HLA-DR antigens by oligonucleotide typing of PCR-amplified DNA. Trans-regulatory nuclear proteins that bind to the Y box in DRB promotors were examined by the gel-mobility shift assay. We found that the trans-regulatory nuclear protein (NF-Y), which binds to the Y box in DRB promoters and which plays a dominant role on the level of the expression and inducibility of DR genes, was absent in 50% of RA patients but not in healthy individuals (0%). Furthermore, we observed that all patients (100%) either lacked the NF-Y protein and/or carried the disease susceptibility DRB1 gene, which gives the highest relative risk value (RR = 46.6; p < 1.6 x 10(-6)) reported so far for susceptibility to RA.

The absence of the trans-regulatory nuclear protein that binds to the Y box with an inverted CCAAT motif in DRB promotors and the presence of the DRB1 gene with the amino acid motif QKRAA and QRRAA cause susceptibility to RA.

To perform a population-based study in rheumatoid arthritis (RA) patients, in order to evaluate the efficacy and safety of pharmacologic treatments. 1087 patients with RA were enrolled; inclusion criteria were: newly diagnosed RA, already diagnosed RA with high disease activity (HDA) (DAS28≥4.2) starting biologic DMARDs (bDMARDs), already diagnosed RA with HDA continuing with conventional DMARDs (cDMARDs). The following data were collected: demographics, clinical and laboratory features, imaging and prescribed drugs. All parameters except immunology and imaging (performed yearly) were repeated at each follow-up evaluations (after 3, 6 and 12 months, and thereafter every 12 months). In order to evaluate clinical response, the EULAR response criteria were used as the gold standard. 414 (38.1%) newly diagnosed patients with RA, 477 (43.9%) RA patients who started bDMARDs and 196 (18.0%) RA patients who continued with cDMARDs were enrolled from April 2012 to March 2015 at 12 Rheumatology Centres in the Emilia Romagna Region. Statistical analyses showed a relative risk ratio (RRR) for moderate response of 1.65 in RA patients who started bDMARDs (p=0.16) and 2.49 for newly diagnosed RA (p=0.01). Sex, age and Health Assessment Questionnaire were not statistically significant. A RRR of 2.00 has been confirmed for RA patients who started bDMARDs (p<0.0005) for a good response as well as 2.20 for newly diagnosed RA (p<0.0005). An increase in adverse events among bDMARDs was found, but when looking at infections or neoplasia, no differences were highlighted between RA which started bDMARDs and RA who continued with cDMARDs.

Our results are in line with already published papers from British and Swedish Registries: a greater likelihood to have a good response is demonstrated for not longstanding RA starting cDMARDs or RA with HDA when a bDMARD is started. Also a good safety profile is demonstrated.

Morning stiffness (MS) is a common problem for patients with rheumatoid arthritis (RA). However the clinical evaluation of the symptom has proved to be difficult. The aim of the study was to determine the responsiveness of two methods for measuring MS. Data from an uncontrolled (n = 63) and a controlled study (n = 80) of inpatient multidisciplinary team care for RA were analyzed. MS was measured by its duration to maximum improvement and by its severity on a visual analog scale (VAS). The responsiveness of both assessment methods was computed by calculating effect sizes and t-statistics, and by receiver operating characteristic (ROC) curves with clinical improvement according to the definition of the American College of Rheumatology as an external criterion. With respect to the ability to detect a clinical improvement between admission and discharge in the uncontrolled study, and a difference in improvement between the treatment and the control group in the controlled study, the effect sizes and t-values of the VAS for severity of MS were consistently higher than those of the duration of MS. In contrast to the duration, the responsiveness of the VAS for MS compared favorably with the responsiveness of other endpoint measures. The ROC surface area of the VAS was higher than that of the duration.

For the evaluation of MS in RA clinical trials, the assessment of MS by a severity score is more responsive than one based on duration and compares favorably with the performance of other endpoint measures.

To compare systolic cardiac function in patients with juvenile dermatomyositis (JDM) with matched controls and examine associations between systolic and diastolic cardiac function and disease variables. Fifty-nine patients, examined at follow-up, median 16.8 years (2-38 years) after disease onset, were compared with 59 age-matched and sex-matched controls. Echocardiography was performed and analysed blinded to patient information. We used mitral annulus displacement to assess the relative long-axis shortening of the left ventricle (long-axis strain) and early diastolic tissue velocity (e'), as markers for systolic and diastolic function, respectively. Disease activity and organ damage were assessed at follow-up by clinical examination and retrospectively by chart review. Long-axis strain was reduced in patients compared with controls (16.6% (2.5) vs 17.7% (2.0), mean (SD), p=0.001), whereas no difference was seen between patients with active and inactive disease. Disease duration correlated with systolic and diastolic function (rsp=-0.50 and rsp=-0.73, both p<0.001) and so did Myositis Damage Index (MDI) 1 year (rsp=-0.36 and rsp=-0.46) and MDI at follow-up (rsp=-0.33 and rsp=-0.60), all p<0.01. High early disease activity score (DAS) in skin (DAS skin 1 year), but not in muscle, predicted systolic (standardised β=-0.28, p=0.011, R(2)=48%) and diastolic dysfunction (β=-0.36, p<0.001, R(2)=72%) at follow-up.

Long-axis strain was reduced in JDM patients compared with controls, suggesting systolic dysfunction. Impaired systolic and diastolic function was predicted by DAS skin 1 year. This indicates a common pathway to two different cardiac manifestations in JDM, perhaps with similar pathogenesis as skin affection.

The choice between unicondylar knee arthroplasty (UKA) and total knee arthroplasty (TKA) is likely to have long-term implications for patient-reported health outcomes. However, high-quality studies that compare the outcomes of TKA and UKA and their effects are still lacking in the literature. Thus, the aim of the present study was to compare the UKA and TKA techniques with regard to functional outcomes and perioperative complications in patients who had isolated medial osteoarthritis. This was a retrospective, single-center, matched-controlled study performed with approval of our hospital (Kunshan hospital of Traditional Chinese Medicine affiliated to Nanjing University of Traditional Chinese Medicine), with the ethics number KZY2020-37. To reduce the effect of selection bias and potential confounding in this observational study, a 1:1 matching algorithm was applied. The groups were split by sex, age to within 6 years, and body mass index within 5 kg/m. Thus, we retrospectively reviewed the records of 240 consecutively enrolled patients who underwent UKA and 240 patients who underwent TKA from January 2013 to June 2015 from the database of our institution. Written informed consent was obtained from all subjects participating in the trial. Clinical outcomes included range of motion, Short Form 12 score, new Knee Society Score, Western Ontario and McMaster Universities Arthritis Index, and the complications. The outcome measures were evaluated by a physiotherapist and were assessed preoperatively and postoperatively at 6 months and 2 years. The mean follow-up time was 3 years. Our study was registered in Research Registry (researchregistry5828).

We hypothesized that there was no significant difference between the 2 groups in terms of postoperative outcomes.

To compare objectively the shape of the intercondylar notch in human osteoarthritic and non-osteoarthritic femora. A sample of 96 human femora from a large skeletal population were selected for study. These femora included subjects with evidence of late stage osteoarthritis (that is, with eburnation present) and subjects with no such evidence. The distal end of the femur, viewed axially, was recorded with a video camera, and digitised computer images were produced. The outline of the intercondylar notch was extracted and represented mathematically as two functions. A functional principal components analysis was used to identify important modes of shape variation. These variations in shape were compared between eburnated and non-eburnated femora. A statistically significant difference in the shape of the intercondylar notch was found between the two groups. The difference related mostly to the shape of the edge of the medial condyle: in the non-osteoarthritic group this tended to exhibit a concavity; in the osteoarthritic group it tended to be straight.

This observed difference may be a predisposing factor to the development of osteoarthritis. The morphology of the intercondylar notch is related to the functioning of and possible damage to the cruciate ligaments, and damage to the cruciate ligaments is a known risk factor for osteoarthritis. Alternatively, this difference may be due to bony remodelling secondary to the onset of osteoarthritis, perhaps in response to altered biomechanics.

To describe and identify factors, in clinical practice, that might be useful increasing the index of suspicion for diffuse idiopathic skeletal hyperostosis (DISH), at a relatively young age. A group of 18 patients with DISH (12.8) who were diagnosed before the age of 50 years (group A) was compare with a group of 20 patients of similar age with osteoarthritis (group B), and 24 patients with DISH diagnosed after the age of 60 years (group C). Data collection included demographic characteristics, body region of main complaint evidence for enthesopathies or tendonitis, length of follow-up, body mass index (BMI), serum lipid profile, family history of diabetes mellitus (DM), and hypertension (HTS). The presence of concomitant diseases and use of medications was recorded at presentation and during the follow-up period. Patients in group A compared with group B, had statistically significant more pain in the lumbar and thoracic spine (P=0.001 and 0.016, respectively), tendonitis/enthesopathies (P=0.004), obesity (BMI> or =30, P=0.014), and first degree relative with HTS and DM (P=0.015 and 0.05, respectively). By the end of the follow-up, significantly more patients in group A were affected by DM compared with group B (P=0.007).

Individuals in the fifth decade of life are likely to be affected by DISH if they are obese, have a first degree relative with either HTS or DM, complain of lumbar or thoracic spinal pain, and are affected by enthesopathies or tendonitis. The likelihood of relatively young patients with > or =3 clinical parameters to be affected with DISH, was six times higher than age and sex matched controls (P=0.004).

The management of patients who are receiving warfarin therapy and have musculoskeletal problems that require treatment with a nonsteroidal antiinflammatory drug (NSAID) is problematic because NSAID use may increase the risk for bleeding. Cyclooxygenase-2 selective NSAIDs such as celecoxib may be less likely to promote gastrointestinal bleeding; however, there are concerns that they could potentiate the anticoagulation effect of warfarin. To determine whether celecoxib potentiates the anticoagulant effect of warfarin, as measured by the international normalized ratio (INR). We performed a randomized, controlled, crossover trial to assess the effect on INR of celecoxib versus codeine (control treatment) in 15 patients who were receiving warfarin therapy and required analgesic treatment for osteoarthritis. During Phase 1 of the study, patients were randomly allocated to receive celecoxib 200 mg/day or codeine phosphate 7-15 mg 3-4 times daily for 5 weeks. During Phase 2 of the study, patients stopped the first study medication and started the other study medication; there was no drug-free interval between phases. Weekly INR testing was performed during the 10 week study period. Adopting the intent-to-treat principle, we used generalized estimating equations to analyze the data. There was no significant difference in the mean INR values during each 5 week treatment period when patients received either celecoxib or codeine. There was, therefore, insufficient evidence to reject the hypothesis that these 2 treatments had an equal effect on the INR (mean difference [95% CI] 0.10 [-0.04 to 0.24]; p = 0.16) based on mean imputation. This finding was confirmed after we repeated the analysis with multiple imputations (mean difference [95% CI] 0.093 [-0.16 to 0.35]; p = 0.47).

Our results suggest that treatment with celecoxib does not potentiate the INR when taken with warfarin. Larger randomized trials are warranted to address the effects of coadministered warfarin and celecoxib on clinical outcomes.

The aim of the present 5-year follow-up was to clarify the nature of occlusal support status and radiographic changes in condyles of the elderly, and the association between these two variables. The present study is part of a comprehensive medical survey of a random sample born in 1904, 1909, and 1914. A total of 364 subjects living in Helsinki participated in the dental part of the examination during 1990 to 1991, and after 5 years a total of 103 were reexamined. Comprehensive data on occlusal support status were available for 94 subjects, and radiographic data were available for 88 subjects. Occlusal support status was assessed on the basis of the Eichner index, radiographic changes were assessed from panoramic radiographs, and symptoms of temporomandibular disorders were assessed using Helkimo's anamnestic index. The most frequent radiographic finding in the mandibular joint was flattening of the articular surface of the condyle associated with osteoarthrosis, found at baseline in 17% and during follow-up in 13% of the subjects. During the 5-year follow-up, Eichner index for natural dentition remained unaltered in 94% of the subjects and in 85% of the subjects when removable dentures were included. There were no radiographic changes in 92% of the cases. No differences based on age or gender were found. A logistic regression model revealed associations between the selected baseline factors. The odds ratio for baseline Helkimo's anamnestic index was 4.1, 5.7 for Eichner index with the support of removable dentures, and 356 for radiographic findings.

Radiographic changes in condyles of elderly people were small during the 5-year follow-up, but baseline radiographic findings, Helkimo's anamnestic index, and Eichner index with removable dentures were risk factors for radiographic findings at the end of the follow-up.