Duration Of Morning Stiffness Research Articles

Morning Stiffness in Elderly Patients with Rheumatoid Arthritis: What is Known About the Effect of Biological and Targeted Agents?

Rheumatoid arthritis (RA) is a chronic inflammatory disease that affects all age groups, but the prevalence appears to increase with age. Elderly-onset RA (after the age of 60years) has distinct clinical patterns. Treatment of RA in older individuals is confounded by the presence of medical comorbidities, concurrent medications, drug interactions, and the altered pharmacokinetics and pharmacodynamics related to aging and organ dysfunction. Patients with RA commonly experience morning stiffness, which is associated with reduced quality of life and work disability. However, despite its importance, morning stiffness is seldom assessed in clinical practice and usually only its duration is measured in the research setting. Whether the intensity, timing, location and impact of this symptom should be assessed in future clinical trials requires further evaluation. The biologic and newer targeted synthetic disease-modifying anti-rheumatic drugs have been shown to be effective in reducing the duration of morning stiffness in patients with RA. Glucocorticoids are a double-edged sword in RA. Although they can effectively reduce inflammation and retard radiological damage (disease modifying), the long-term use of glucocorticoids is associated with numerous adverse effects. Thus, glucocorticoids should be used for short-term treatment of RA only. Night-time administration of glucocorticoids has been shown to alleviate morning stiffness and should be considered in patients with serious morning joint stiffness symptoms.

Treatment of Rheumatoid Arthritis by Bee-venom Acupuncture

To study the clinical efficacy and safety of bee-venom acupuncture therapy for rheumatoid arthritis (RA). A total of 120 cases of RA patients were randomized into bee-sting acupuncture group (treatment) and western medicine group (control) in accordance with the random number table. The patients of the control group were treated by oral administration of Methotrexate (10 mg, once a week) and Celecoxlb (0.2 g, once a day), and those of the treatment group treated by 5 to 15 bee stings of Ashi-points or acupoints according to different conditions and corporeity, and with the bee-sting retained for about 5 min every time, once every other day. The treatment lasted for 8 weeks. The therapeutic effect was assessed by examining symptoms and signs of the affected joints as morning stiffness duration, swollen/tender joint counts (indexes), handgrip strength, 15 m-walking time, visual analogue scale (VAS), Disease Activity Score including a 28-joint count (DAS 28), rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), anti-cyclic citrullinated peptide antibody (ACCPA); and for assessing the safety of bee-venom acupuncture, the patients' responses of fever, enlargement of lymph nodes, regional red and swollen, itching, blood and urine tests for routine were examined. Findings of DAS 28 responses displayed that of the two 60 cases in the control and bee-venom acupuncture groups, 15 and 18 experienced marked improvement, 33 and 32 were effective, 12 and 10 ineffective, with the effective rates being 80% and 83. 33%, respectively. No significant difference was found between the two groups in the effective rate (P>0.05). After the treatment, both groups have witnessed a marked decrease in the levels of morning stiffness duration, arthralgia index, swollen joint count index, joint tenderness index, 15 m walking time, VAS, RF, ESR, CRP and ACCPA, and an obvious increase of handgrip strength relevant to their own levels of pre-treatment in each group (P<0.05). There were no significant differences between the two groups in the abovementioned indexes (P>0.05). The routine blood test, routine urine test, routine stool test, electrocardiogram result, the function of liver and kidney and other security index were within the normal range, without any significant adverse effects found after bee-stinging treatment. Bee-venom acupuncture therapy for RA patients is safe and effective, worthy of popularization and application in clinical practice.

Using Rheumatoid Arthritis Disease Activity Index-5 questionnaire in the assessment of disease activity in patients with rheumatoid arthritis: correlation with quality of life, pain, and functional status

ObjectiveThe aim of our study was to assess the disease activity in patients with rheumatoid arthritis (RA) using Rheumatoid Arthritis Disease Activity Index-5 (RADAI-5) questionnaire and to find its correlation with Disease Activity Score-28 (DAS28), quality of life, pain, and functional status.Patients and methodsA total of 40 patients with RA were included. Quality of life was evaluated by Quality of Life–Rheumatoid Arthritis scale. The severity of pain was measured by 100-mm visual analog scale-pain. Health Assessment Questionnaire Disability Index was used to evaluate functional status. Disease activity was measured by using the DAS28 and RADAI-5.ResultsMean RADAI-5 score was 4.2±1.7 (moderate disease activity). A total of seven (17.5%) patients were in remission, four (10%) patients had mild disease activity, 19 (47.5%) patients had moderate disease activity, and 10 (25%) patients had high disease activity. RADAI-5 was significantly correlated with DAS28, quality of life scale, pain scale, and functional status (r=0.9, P<0.001; r=0.9, P<0.001; r=0.4, P=0.02; and r=0.6, P<0.001, respectively). Moreover, RADAI-5 was found to be significantly correlated with morning stiffness duration, Ritchie articular index, tender 28-joint count, swollen 28-joint count, erythrocyte sedimentation rate, anticyclic citrullinated peptide, and rheumatoid factor positivity (r=0.3, P=0.03; r=0.8, P<0.001; r=0.9, P<0.001; r=0.7, P<0.001; r=0.6, P<0.001; r=0.6, P<0.001; and r=0.4, P=0.008, respectively).ConclusionRADAI-5 is a simple and low-cost self-report questionnaire that reflects patients’ perception of signs and symptoms. The correlations of RADAI-5 with DAS28, quality of life, pain, and functional status reflect its value in the assessment of disease activity in patients with RA.

Association of interleukin-6 and its -174G/C promoter polymorphism with clinical and laboratory characteristics of non hepatitis C virus rheumatoid arthritis patients

BackgroundInterleukin-6 is a cytokine protein, which causes inflammation, maintains immune homeostasis and shows a role in rheumatoid arthritis pathogenesis. IL-6-174G/C promoter polymorphism may have a role in susceptibility to RA. Aim of the workTo evaluate the clinical significance of serum levels of IL-6 and its -174G/C promoter polymorphism in RA patients in comparison with the controls. Patients and methodsThis study enrolled 25 non hepatitis C virus RA patients versus 25 age and gender matched controls. Demographic, clinical and laboratory data were prospectively evaluated. Serum IL-6 level and promoter (-174G/C) genotype were determined. ResultsSerum IL-6 levels was significantly higher in RA patients compared to control subjects (p = .001), especially those with CC promoter polymorphism. There was a significant correlation between IL and 6 level and duration of morning stiffness, disease activity, hemoglobin concentration and ESR level. 15/25 patients had (-174G/G) gene promoter polymorphism, 8/25 were GC and 2/25 were CC. All controls were GG. There was significant association between gene polymorphism and age at disease onset (p = .0172), which was older in those with GG genotype (38.5 ± 10.25 years) than those with CC (33.5 ± 0.71 years) and younger in GC genotypes (27.9 ± 7.9 years). None of the other clinical, laboratory or radiological parameters would predict the IL-6 promoter polymorphism. ConclusionSerum IL-6 levels and -174G/C promoter polymorphism were higher in RA patients than in healthy controls. The positive correlation of IL-6 level with the DAS28 and duration of morning stiffness may confirm its’ increased involvement in the pathogenesis of RA and may point to the need for considering of anti-IL-6 agents in their management plan. The negative correlation of IL-6 level with the hemoglobin level may confirm IL-6 play a significant role in anemia of RA.

The impact of anti-cyclic citrullinated peptide antibody status on the management of patients with early rheumatoid arthritis: observational study results from Lithuania.

Background.To provide data on the use of anti-cyclic citrullinated peptide antibody (anti-CCP) and other routinely used clinical parameters and to assess the impact of anti-CCP status on therapeutic decisions, an observational study was conducted in patients with rheumatoid arthritis (RA).Methods.Sixty-seven adult patients with a recent diagnosis of RA were recruited from four rheumatology centres in Lithuania and were prospectively observed for 12 months. Data collection was based on the review of medical records and routine examination of patients. Patients completed the Health Assessment Questionnaire – Disability Index and Patient Global Assessment of disease activity using a visual analogue scale. Physicians were asked about the importance of the anti-CCP results and other factors important for therapeutic decisions.Results.Of the 67 patients enrolled, 54 (80.6%) completed the study. At the beginning of the study, physicians considered anti-CCP results to be important for decision-making in 87.0% of patients. The perceived importance of anti-CCP results did not change significantly throughout the study. After one year of treatment, factors that were considered more important than the anti-CCP results included the presence of erosions, significantly increased C-reactive protein, duration of morning stiffness, multi-articular expanding, and rheumatoid factor status. For nearly half of the patients (n = 26; 48.1%), physicians would not change the treatment strategy if the patient had the opposite anti-CCP results at baseline.Conclusions.The study revealed that decision-making in the management of RA was based on multifactorial data. The role of anti-CCP as a single test in treatment decisions needs further investigation.

Meta-analysis on efficacy and safety of combination therapy of Aconitum and Western medicine in treatment of rheumatoid arthritis

To analyze the efficacy and safety of the combination therapy of Aconitum and Western medicine in the treatment of rheumatoid arthritis (RA) by Meta-analysis, and provide evidence for its clinic application for RA. The random clinical trials (RCTs) regarding the combination therapy for treating RA were retrieved in the database of China National Knowledge Infrastructure database, China Science and Technology Journal database, WanFang, Chinese Biomedical Medical Database, PubMed, and Cochrane Library up to July 2017. According to the given inclusion criteria, 8 RCTs involving 659 participants were included, and the included RCTs could be further divided into three subgroups according to the herb type, which were Aconiti Radix (Chuanwu) subgroup (6RCTs), Aconiti Kusnezoffii Radix (Caowu) subgroup (1RCT), and Chuanwu-Caowu subgroup (1RCT). The Meta-analysis results indicated that as compared with Western medicine, the combined use of Aconitum and Western medicine, no matter Chuanwu, Caowu or Chuanwu-Caowu subgroups, could improve the total effective rate of RA (6RCTs, RR=1.19, 95%CI [1.10, 1.28], P<0.000 01), (1 RCT, RR=1.43, 95%CI [1.18, 1.73], P=0.000 2), (1 RCT, RR=1.27, 95%CI [1.02, 1.58], P=0.03) respectively. The combined use of Aconitum and Western medicine was also effective on the number of joint swelling, duration of morning stiffness, patients' handgrip, and the erythrocyte sedimentation rate, C-reactive protein and rheumatoid factor. However, its action was not significant on joint tenderness. And also, in the included RCTs, there were 34 cases of adverse drug reactions/events (ADR/ADE) in the Chuanwu subgroup, while 86 cases in the Western medicine control group. The ADR/ADE incidence was even more lower in Chuanwu-Caowu subgroup, but no difference between Caowu subgroup and Western medicine group. Based on the included RCTs, the combined use of Aconitum and Western medicine could achieve more satisfying efficacy and lower ADRs incidence for RA as compared with Western medicine alone. However, due to the limitation in the not-high quality of included RCTs and the lack of large-scale multi-center research, the results still need to be further validated in the clinic application.

Poor quality of life in indian ankylosing spondylitis patients

Background: Ankylosing Spondylitis (AS) is a chronic inflammatory disease that leads to significant disability. We sought to study the impact of the disease activity and functional impairment on QoL in Indian patients with AS. Methods: World Health Organization- Quality of Life-BREF (WHOQoL-BREF) questionnaire was used to measure quality of life (QoL) in 99 adults with AS (modified Rome criteria), 72 healthy individuals, and 20 rheumatoid arthritis patients. Apart from demographic variable such as age, gender, clinical manifestations, and treatment received, disease activity parameters such as duration of early morning stiffness, BASDAI, swollen and tender joint count, Erythrocyte Sedimentation Rate (ESR) and C Reactive Protein (CRP) were also recorded. Presence of damage was assessed using spinal radiographs. All values are in median (IQR). Results: Out of the 99 patients, 5 were females and 5 had juvenile onset AS. Median age was 32 (26-42) years and median disease duration was 6 (1.25-10) years. Forty-three had peripheral arthritis and 18 had enthesitis. Syndesmophytes were present on spinal radiographs in 54 cases. BASDAI correlated negatively with the physical, psychological and environmental domains (P Conclusion: Indian AS patients have poorer quality of life than patients with rheumatoid arthritis and healthy individuals, possibly due to poor control of disease activity.

Can hybrid hyaluronic acid represent a valid approach to treat rizoarthrosis? A retrospective comparative study

BackgroundOsteoarthritis (OA) of the trapeziometacarpal joint (TMJ) is a disabling condition with a significant impact on quality of life. The optimal management of hand OA requires a combination of non-pharmacological and pharmacological treatments that include intra-articular (i.a.) therapy. EULAR experts recommend corticosteroid injections in TMJ OA and underline the usefulness of hyaluronic acid (HA). The aim of this study was the assessment of the efficacy and tolerability of i.a. injections of a hybrid formulation of HA (Sinovial H-L®) in comparison to triamcinolone in patients with TMJ OA.MethodsThis 6-months observational comparative study, retrospective analyzed the medical records of 100 patients with monolateral or bilateral TMJ OA, treated with two injections of Sinovial H-L® (Sinovial H-L Group) or of triamcinolone acetonide (Triamcinolone Group). Clinical assessments were recorded at the time of the first and second injection and after one, 3 and 6 months.The primary outcomes were the change in global pain on a Visual Analogue Scale (VAS) and in hand function evaluated by the Functional Index for Hand OA (FIHOA) from baseline to month 6. Secondary outcomes were the improvement of the duration of morning stiffness, Health Assessment Questionnaire (HAQ) and the Medical Outcomes Study 36-Item Short Form (SF-36). The comparison between the two groups of treatment were performed with the Wilcoxon rank-sum test for continuous variables and with chi-square or Fisher exact test for categorical variables. Statistical significance was set at p < 0.05.ResultsBoth therapies provided effective pain relief and joint function improvement, but the benefits achieved were statistically significantly superior in the Sinovial H-L Group than the Triamcinolone Group after one month (p < 0.01) from the beginning of the therapy and during the 6-months follow-up (p < 0.001). Furthermore, Sinovial H-L® was associated with a significant decrease in the duration of morning stiffness and with a significant improvement in the HAQ score and physical component summary (PCS)-SF-36.ConclusionsOur results suggested that the hybrid formulation of HA may be more effective than triamcinolone in pain relief and joint function improvement with a rapid and persistent effect, resulting a valid alternative to steroid in the management of TMJ OA.Trial registrationClinicalTrials.gov, date of registration: June 14, 2017, NCT03200886. The present trial was retrospectively registered.

Effectiveness, safety and drug survival of tumor necrosis factor-α inhibitors in the treatment of spondyloarthritis: A real-life study in Tunisia

Aim of the workThe aim of the present study was to evaluate effectiveness of anti-tumor necrosis factor-α (anti-TNFα) in the treatment of spondyloarthritis (SpA) and to assess their safety and drug survival. Patients and methodsForty-two SpA patients (33 men, 9 women) were retrospectively studied. The disease was progressive in all patients. Response was assessed after 6 months using Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Functional Index (BASFI) scores and other clinical parameters. A major clinical response was defined as 50% improvement of the initial BASDAI. Patients were grouped into those with ankylosing spondylitis (AS) (24 patients) or psoriatic arthritis (PsA) and enteropathic arthritis (EA) (18 patients) and the response to anti-TNF was compared. ResultsThe mean age of the patients was 41.3 ± 9.7 years and disease duration 14.6 ± 8.2 years. After 6 months, 74% of patients were BASDAI 50 responders. The mean BASDAI and BASFI scores varied from 56 ± 20 and 61.8 ± 26 to 19 ± 19 and 24 ± 25 respectively (p < .001). The two SpA groups had the same effectiveness profile. The comparison between them showed a greater reduction of morning stiffness duration and erythrocyte sedimentation rate in patients with PsA or EA (p = .04). At least, one adverse event developed by 48% of patients and it was severe in 12%. Bronchopulmonary infections were the most frequent (8 patients). Drug survival rate was estimated at 86% after 1 year of treatment. ConclusionAnti-TNFα therapy has a good response rate in SpA patients and an acceptable safety profile which explains the high drug survival rates.

Aquaporin-1 expression as an indicator in evaluating the efficacy of meloxicam in the treatment of ankylosing spondylitis: A comparative study

ObjectiveThe key objective of the study was to investigate the correlation between the expression of aquaporin-1 (AQP1) and the efficacy of meloxicam and expressions of pro-inflammatory cytokines in ankylosing spondylitis (AS). Methods40 AS patients whom had received meloxicam were recruited and subsequently placed into the experiment, while 40 healthy individuals were recruited as control group. Clinical indicators were detected before treatment (0 week), and at 2, 4, 6, 8, 10 and 12 week intervals after treatment, which included various assessments including Ankylosing Spondylitis 20% (ASAS20) response, Bath ankylosing spondylitis disease activity index (BASDAI), visual analog scale (VAS) for back pain, duration of morning stiffness, Bath ankylosing spondylitis functional index (BASFI), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) levels. Healthy volunteers were examined for ESR and CRP levels. The mRNA and protein expressions of AQP1 and pro-inflammatory cytokines, tumor necrosis factor-α (TNF-α) and interleukin-2 (IL-2), in peripheral blood mononuclear cells (PBMCs) were detected 6 and 12 weeks after treatment using reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blotting. Correlation of expressions of AQP1, efficacy of meloxicam and expression of pro-inflammatory cytokines were determined via Pearson correlation analysis. ResultsFollowing 12 weeks of meloxicam treatment, the ASAS20 response reached 93.7±3.61%. 6 weeks after treatment, BASDAI, VAS for back pain, duration of morning stiffness, BASFI, ESR, and CRP levels all exhibited considerably reduced levels compared to the initial levels observed prior to the commencement of treatment. Compared with before treatment, the expressions of TNF-α, IL-2 and AQP1 mRNA and protein all displayed decreases in the experiment group after both 6 and 12-week periods of treatment. Pre and post treatment levels of TNF-α, IL-2 and AQP1 mRNA and protein expressions were higher than those in the control group. The expressions of AQP1 mRNA and protein in the experiment group were positively correlated with clinical indicators and expressions of pro-inflammatory cytokines. ConclusionOur findings indicated that AQP1 was both highly expressed and positively correlated with the efficacy of meloxicam and expressions of pro-inflammatory cytokines in AS patients, thereby highlighting the promise of meloxicam as a potential indicator in predicting the efficacy in the treatment of AS.

Correlation of the expression of miR-146a in peripheral blood mononuclear cells of patients with ankylosing spondylitis and inflammatory factors.

We investigated the expression of miR-146a in peripheral blood mononuclear cell (PBMC) of patients with ankylosing spondylitis (AS) and its correlation with inflammatory factors to explore the clinical significance. In total 45 patients with AS were selected at the Weifang People's Hospital from June, 2014 to January, 2016. At the same time, 30 healthy volunteers were also selected to serve as control group. Expression level of miR-146a in PBMC cells of patients in each group was detected by quantitative real-time-polymerase chain reaction (qRT-PCR). Levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and IL-6 in serum and the supernatant of culture medium of PBMC derived from each group were detected by enzyme-linked immunosorbent assay (ELISA). Correlations between expression level of miR-146a and serum inflammatory factors, and clinical indicators were analyzed. Clinical indicators included bath ankylosing spondylitis disease activity index (BASDAI), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and duration of morning stiffness. Expression level of miR-146a in PBMC of AS patients was significantly higher than that of healthy control (P<0.01); levels of TNF-α, IL-1β and IL-6 in serum and the supernatant of culture medium of PBMC derived from AS patients were significant compared to those of control group (P<0.01); expression of miR-146a in PBMC of patients with AS was positively correlated with the levels of TNF-α, IL-1β and IL-6 in serum (r=0.632, P<0.01; r=0.574, P<0.01; r=0.483, P<0.01). In addition, expression level of miR-146a in PBMC of patients with AS was positively correlated with BASDAI, ESR, CRP and duration of morning stiffness (r=0.551, P<0.01; r=0.738, P<0.01; r=0.685, P<0.01; r=0.497, P<0.01). Expression level of miR-146a in PBMC of AS patients was significantly increased and the expression level was positively correlated with the levels of TNF-α, IL-1β and IL-6 in serum (P<0.05). In addition, expression level of miR-146a in PBMC of AS patients was also positively correlated with BASDAI, ESR, CRP and duration of morning stiffness. Those results suggest that miR-146a may be involved in the pathogenesis of AS, and the expression level of miR-146a in PBMC cells may be helpful for diagnosis of AS and judgment of disease activity.

Nursing sensitive outcomes in patients with rheumatoid arthritis: A systematic literature review

BackgroundAlthough rheumatology nursing has been shown to be effective in managing patients with rheumatoid arthritis, patient outcomes sensitive to nursing interventions (nursing sensitive outcomes) have not been systematically studied. ObjectivesThe objective of this study was to identify and delineate relevant patient outcomes measured in studies that reported nursing interventions in patients with rheumatoid arthritis. DesignA systematic search was conducted from 1990 to 2016. Inclusion criteria were (i) patients with rheumatoid arthritis, (ii) adult population age ≥16years, (iii) nurse as part of the care team or intervention delivery, (iv) primary research only, (v) English language, and (vi) quantitative studies with nursing sensitive outcomes. Data sourcesMedline, CINAHL, Ovid nursing, Cochrane library and PsycINFO databases were searched for relevant studies. Review methodsUsing the predetermined inclusion/exclusion criteria, nine reviewers working in pairs assessed the eligibility of the identified studies based on titles and abstracts. Papers meeting the inclusion criteria were retrieved and full texts were further assessed. Critical Appraisal Skills Programme tools were used to assess the quality of the included studies. Data on nursing sensitive outcomes were extracted independently by two reviewers. The Outcome Measures in Rheumatology comprehensive conceptual framework for health was used to contextualise and present findings. ResultsOf the 820 articles retrieved, 7 randomised controlled trials and 3 observational studies met the inclusion criteria. Seventeen nursing sensitive outcomes were identified (disease activity, clinical effects, pain, early morning stiffness duration, fatigue, patient safety issues, function, knowledge, patient satisfaction, confidence in care received, mental health status, self-efficacy, patient attitude/perception of ability to control arthritis, quality of life, health utility, health care resources, death). These fitted into 10 health intervention domains in keeping with the pre-specified conceptual framework for health: disease status, effectiveness, safety, function, knowledge, satisfaction, psychological status, quality of life, cost, death. A total of 59 measurement instruments were identified comprising patient reported outcome measures (n=31), and biologic measures and reports (n=28). ConclusionsThis review is notable in that it is the first to have identified, and reported, a set of multidimensional outcome measures that are sensitive to nursing interventions in rheumatology specifically. Further research is required to determine a core set of outcomes to be used in all rheumatology nursing intervention studies.

Les arthralgies à risque de progression vers une polyarthrite rhumatoïde

Some patients consulting for arthralgia are at high risk of progression to clinical arthritis and/or rheumatoid arthritis. Individual risk assessment relies on physical examination: presence of a first-degree relative with RA, symptoms located in metacarpophalangeal joints, duration of morning stiffness≥60minutes, history of swollen joints as reported by the patient, difficulty with making a fist, positive squeeze test of metacarpophalangeal joints. It also relies on identification of biomarkers: C reactive protein level, presence of ACPA and/or rheumatoid factor. It finally relies on joint imaging: ultrasound and/or MRI features of joint inflammation. At the end of individual risk assessment, the rheumatologist may address potentially modifiable risk factors of progression to rheumatoid arthritis such as smoking status and body mass index. In those individuals at highest risk of progression to rheumatoid arthritis, he may consider initiating an immunomodulatory agent to prevent arthritis development even if the level of evidence is still low in this situation.

Switching From Immediate-Release to Delayed-Release Prednisone in Moderate to Severe Rheumatoid Arthritis: A Practice-Based Clinical Study.

IntroductionRheumatoid arthritis (RA) produces debilitating morning stiffness. Exogenous glucocorticoids can help with these symptoms when timed appropriately. Bedtime dosing of delayed-release prednisone (DR-prednisone) matches the rise of inflammatory cytokines before awakening and can improve stiffness and other RA symptoms. A prospective open-label study was conducted in patients currently on stable doses of immediate-release prednisone (IR-prednisone) who were switched to DR-prednisone to analyze the incremental benefit of better timed and lower dose glucocorticoid therapy.MethodsTwelve US sites enrolled patients with moderate-severe RA into a 12-week prospective study. Patients were switched from IR- to DR-prednisone while maintaining other existing background therapies. Change from baseline in morning stiffness severity, morning stiffness duration, swollen and tender joint counts (S-TJC), 28 joint disease activity score (DAS28), and patient/physician global assessment (PGA/PhGA), among others, were measured. Post-hoc analyses were performed on those completing 10 weeks of treatment and those with >60 min of morning stiffness at baseline.ResultsFifty-six patients had at least one follow-up visit and were similar in demographics to previous controlled trials with DR-prednisone with regard to baseline age and DAS28-CRP but had lower morning stiffness and RA duration. DR-prednisone produced a trend toward lower morning stiffness severity and duration with a reduction in daily prednisone dose of almost 1 mg. Patients treated with DR-prednisone for ≥10 weeks demonstrated significant reductions in morning stiffness duration, SJC, TJC, DAS28-CRP, and PhGA (all p ≤ 0.04). Patients treated for ≥10 weeks with >60 min of baseline morning stiffness produced similar results in these measures as well as a 21% reduction in morning stiffness severity (p = 0.02).ConclusionPatients switched to DR-prednisone from IR-prednisone in this practice-based study maintained or improved their outcomes across a variety of domains, and results were comparable to previous controlled trials in which patients completed at least 10 weeks of treatment.FundingHorizon Pharma USA, Inc.Trial RegistrationClinicalTrials.gov identifier, NCT02287610.

Power Color Doppler and Spectral Doppler Ultrasonography to Evaluate Response to Intra-articular Steroid Injection in Knee Joints in Juvenile Idiopathic Arthritis.

To evaluate the role of ultrasonographic indices (Color Fraction and Resistive Index) in assessing the effect of intra-articular steroid (IAS) injection on synovial inflammation in knee joints of Juvenile Idiopathic Arthritis (JIA) patients and to determine the correlation between these ultrasonographic indices and clinical and laboratory parameters in JIA patients after IAS. Twenty seven patients of JIA and equal number of age and sex matched healthy controls were enrolled. Thirty six knee joints were injected with IAS. Duration of morning stiffness, swelling score, tenderness score, range of motion, visual analogue scale for pain, Physician global assessment of disease activity, Patient/Parent assessment of general well being, Juvenile Arthritis Disease Activity Score, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), synovial thickness, synovial effusion, Color fraction (CF) and Resistive index (RI) were measured at base line and at one and two months of follow-up. At baseline, a significant difference was found in ESR, CRP, CF and RI values between cases and controls. A significant decrease in various clinical, core set variables and ultrasonographic parameters was observed at each follow-up. Synovial thickness, synovial effusion and CF decreased by 51.78%, 64.67% and 49.35% respectively and range of motion and RI increased by 166% and 31.94% respectively at second follow-up. Both CF and RI showed a significant correlation with active joint count. Both CF and RI had a high inter and intra-class correlation. Power Color Doppler and Spectral Doppler ultrasonographic indices (CF and RI) may have a role in assessment of the response to IAS injection of inflamed knee joints.

A systemic review and meta-analysis of the clinical efficacy and safety of total glucosides of peony combined with methotrexate in rheumatoid arthritis

To assess the efficacy and safety of the combination of total glucoside of peony (TGP) and methotrexate (MTX) for the treatment of rheumatoid arthritis (RA). Randomized controlled trial (RCT) data on the traditional Chinese active component TGP combined with MTX vs. MTX alone for the treatment of RA was collected by searching the Pubmed, Embase, Cochrane Library, CNKI, VIP Journals database, and Wanfang database up to February 2017. Study selection, data extraction, data synthesis, and data analyses were performed according to the Cochrane standards. A total of eight RCTs involving 522 participants were included in this meta-analysis. Compared with MTX alone, the use of TGP combined with MTX exhibited better therapeutic effects for the treatment of RA (P = 0.004). In addition, TGP combined with MTX caused a more significant decrease in erythrocyte sedimentation rate (ESR) (P < 0.0001) and swollen joint count (SJC) (P < 0.00001). However, no significant differences were found in C-reactive protein (CRP) (P = 0.19), duration of morning stiffness (DMS) (P = 0.32), or tender joint count (TJC) (P = 0.23) between the two groups. In addition, adverse events were more frequently reported in the MTX monotherapy group than in the TGP and MTX combination group (P = 0.0007). Our study demonstrates that TGP combined with MTX is more effective than MTX alone for the treatment of RA. Nevertheless, the adverse effects of the combination of TGP and MTX need to be further assessed. Due to the poor methodological quality of included trials, well-designed, multi-center, and large-scale RCTs are necessary to draw a more definitive conclusion.

The effect of tocilizumab on clinical signs and laboratory findings in rheumatoid arthritis patients resistant to methotrexate

Rheumatoid arthritis (RA) is a chronic systemic autoimmune inflammatory disease that mainly affects joint damage followed by increased morbidity and mortality rates. The progressive increase of inflammation factors, especially IL-6, is seen during the course of this condition. The aim of this study was to evaluate the effect of tocilizumab (TCZ) in patients with severe to moderate resistant RA with an inadequate response to treatment with disease-modifying antirheumatic drugs (DMARDs). We also reviewed the safety of the drug and related complications. Twelve selected RA patients received 8 mg/kg of TCZ every 4 weeks for over 24 weeks; we evaluated inflammatory factor like ESR, lipid profile, comprehensive physical exam, and RA activity like Disease Activity Score (DAS) 28, Short Form (36) Health Survey (SF-36), and ACR50 to calculate the swollen and tender joint counts. DMARDs were simultaneously administered. First-level response and secondary response were defined as reaching the American College of Rheumatology 20% response criteria (ACR20) within 24 weeks of treatment and Disease Activity Score (DAS) 28, Short Form (36) Health Survey (SF-36), and ACR50, respectively. All patients achieved ACR20 after 24 weeks and 83% reached ACR50 (p < 0.001). DAS28 decreased from 6.93 ± 2.11 at baseline to 1.29 ± 0.95 at the end of 28 weeks (p < 0.001). SF-36 increased from 28 ± 1.43 to 61.42 ± 15.66 at the end of the study (p < 0.001). SF-36 physical component summary scores also increased from 42 ± 4.98 at baseline to 88.17 ± 2.96 at the end of the study (p < 0.001). We observed that TCZ caused a rapid and sustained improvement in all disease activity indicators such as CRP, ESR, swelling and tender joint count, and morning stiffness duration in RA patients’ refractory to methotrexate.

Alfredson versus Silbernagel exercise therapy in chronic midportion Achilles tendinopathy: study protocol for a randomized controlled trial

BackgroundMidportion Achilles tendinopathy (AT) is a common overuse injury, usually requiring several months of rehabilitation. Exercise therapy of the ankle plantar flexors (i.e. tendon loading) is considered crucial during conservative rehabilitation. Alfredson’s isolated eccentric and Silbernagel’s combined concentric-eccentric exercise programs have both shown beneficial results, but it is unknown whether any of these programs is superior for use in clinical practice. Therefore, the primary objective of this study is to compare the effectiveness of both programs on clinical symptoms. Secondary objectives are to compare the effectiveness of both programs on quality of life and functional outcome measures, to investigate the prognostic value of baseline characteristics, to investigate differences in cost-effectiveness.Methods/DesignEighty-six recreational athletes (21–60 years of age) with unilateral chronic midportion AT (i.e. ≥ 3 months) will be included in this multicenter assessor blinded randomized controlled trial. They will be randomly allocated to either a group performing the Alfredson isolated eccentric training program (n = 43), or a group performing the Silbernagel combined concentric-eccentric program (n = 43). In the Alfredson group, participants will perform eccentric heel-drops on their injured side, twice daily for 12 weeks, whereas in the Silbernagel group, participants perform various concentric-eccentric heel-raise exercises, once daily for 12 weeks. Primary outcome measure will be the Victorian Institute of Sport Assessment – Achilles (VISA-A) questionnaire. Secondary outcomes will be a visual analogue scale (VAS) for pain during daily activities and sports, duration of morning stiffness, global perceived effect, the 12-item Short Form Health Survey and the Euroqol instrument, and functional performance measured with the heel-raise test and the countermovement jump. Additionally, alongside the RCT, a cost-effectiveness analysis will be performed. Assessments will be performed at baseline and after 12, 26, and 52 weeks.DiscussionThis study is the first to directly compare the Alfredson and the Silbernagel exercise program in a randomized trial. The results can further enlarge the evidence base for choosing the most appropriate exercise program for patients with midportion AT.Trial registrationDutch Trial register: NTR5638. Date of registration: 7 January 2016.

Patient-reported Outcomes as Predictors of Change in Disease Activity and Disability in Early Rheumatoid Arthritis: Results from the Yorkshire Early Arthritis Register.

To assess patient-reported variables as predictors of change in disease activity and disability in early rheumatoid arthritis (RA). Cases were recruited to the Yorkshire Early Arthritis Register (YEAR) between 1997 and 2009 (n = 1415). Predictors of the 28-joint Disease Activity Score (DAS28) and the Health Assessment Questionnaire-Disability Index (HAQ-DI) at baseline and change over 12 months were identified using multilevel models. Baseline predictors were sex, age, symptom duration, autoantibody status, pain and fatigue visual analog scales (VAS), duration of early morning stiffness (EMS), DAS28, and HAQ-DI. Rates of change were slower in women than men: DAS28 fell by 0.19 and 0.17 units/month, and HAQ-DI by 0.028 and 0.023 units/month in men and women, respectively. Baseline pain and EMS had small effects on rates of change, whereas fatigue VAS was only associated with DAS28 and HAQ-DI at baseline. In patients recruited up to 2002, DAS28 reduced more quickly in those with greater pain at baseline (by 0.01 units/mo of DAS28 per cm pain VAS, p = 0.024); in patients recruited after 2002, the effect for pain was stronger (by 0.01 units/mo, p = 0.087). DAS28 reduction was greater with longer EMS. In both cohorts, fall in HAQ-DI (p = 0.006) was greater in patients with longer EMS duration, but pain and fatigue were not significant predictors of change in HAQ-DI. Patient-reported fatigue, pain, and stiffness at baseline are of limited value for the prediction of RA change in disease activity (DAS28) and activity limitation (HAQ-DI).

Development and testing of candidate items for inclusion in a new rheumatoid arthritis stiffness patient-reported outcome measure

To qualitatively develop and test a set of candidate items for a new RA stiffness patient-reported outcome measure (PROM) that capture the patient perspective. This is an essential first step in PROM development, prior to quantitative development, assessment and validation. Focus groups further examined the previously developed stiffness conceptual model and explored the patient perspective regarding stiffness assessment. Data were analysed using thematic analysis. An iterative process of item development was then performed by the expert study team of researchers, patients and clinicians, based on the two qualitative datasets and informed by measurement theory and guidelines. Finally, these candidate items were tested using formal cognitive interview methodology and subsequently refined. Sixteen RA patients from the UK participated in focus groups. Data confirmed the conceptual model of the RA patient experience of stiffness and provided insight into stiffness assessment, including suggestions regarding patient-relevant stiffness assessment categories such as impact, location and timing. These data informed the development of 77 candidate stiffness PROM items, including multiple formats for some. Eleven RA patients participated in cognitive interviews. Minor changes were made to items to enhance understanding and 32 items were removed, resulting in 45 candidate PROM items. Rigorous qualitative methodology and considerable patient involvement has underpinned items for a new RA stiffness PROM with strong content validity. Crucially, patient involvement broadened assessment beyond early morning stiffness duration, which may address existing PROM limitations. Items are now suitable for quantitative item reduction, structural development of the final PROM and validation.