Probing motor dynamics at the muscle level-Acoustic myography in Parkinson's disease.

Acoustic myography (AMG) noninvasively probes muscle activity. We explored whether AMG captures abnormal motor activity in patients with Parkinson's disease (PD) and how this activity is modulated by antiparkinsonian medication. Twenty patients with PD underwent AMG of the biceps, triceps, extensor carpi radialis longus, and adductor policis muscles of the more affected arm during active and passive movements, using a mobile AMG device (CURO, Denmark). AMG and assessment of motor symptoms were performed in a pragmatic off-medication state, as well as one and 3 h after oral intake of 200 mg levodopa. Three AMG parameters were calculated using the CURO analysis system. Motor efficiency was expressed by the E-score, muscle fiber recruitment by the temporal T-score, spatial summation by the S-score, and S/T ratio. Twenty age- and sex-matched healthy subjects served as controls. Group mean values were statistically compared using unpaired two-tailed adjusted t-test and ANOVA with Tukey´s correction for multiple comparison (p ≤ 0.05). For the biceps and extensor carpi radialis longus muscles, the active movement S:T ratio was lower in PD relative to healthy controls. The E-score was also lower during active and passive flexion/extension movements in the off-medication state. No significant between-group differences in the AMG scores were noted for the triceps muscle during active or passive movements. The active S:T ratio and the E-score during active elbow flexion and extension may offer a useful means to quickly assess abnormal motor activity and the effect of drug treatment in PD.

Pain and pain mechanisms in patients with inflammatory arthritis: A Danish nationwide cross-sectional DANBIO registry survey.

BACKGROUND: Central pain mechanisms may be prominent in subsets of patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and other spondyloarthritis (SpA). The painDETECT questionnaire (PDQ) identifies neuropathic pain features, which may act as a proxy for centrally mediated pain. The objectives were to quantify and characterize pain phenotypes (non-neuropathic vs. neuropathic features) among Danish arthritis patients using the PDQ, and to assess the association with on-going inflammation. METHODS: The PDQ was included onto the DANBIO touch screens at 22 departments of Rheumatology in Denmark for six months. Clinical data and patient reported outcomes were obtained from DANBIO. A PDQ-score >18 indicated neuropathic pain features, 13-18 unclear pain mechanism and <13 non-neuropathic pain. RESULTS: Pain data (visual analogue scale, VAS) was available for 15,978 patients. 7,054 patients completed the PDQ (RA: 3,826, PsA: 1,180, SpA: 1,093). 52% of all patients and 63% of PDQ-completers had VAS pain score ≥ 30 mm. The distribution of the PDQ classification-groups (<13/ 13-18/ >18) were; RA: 56%/24%/20%. PsA: 45%/ 27%/ 28%. SpA: 55% / 24%/ 21%. More patients with PsA had PDQ score >18 compared to RA and SpA (p<0.001). For PDQ > 18 significantly higher scores were found for all patient reported outcomes and disease activity scores. No clinical difference in CRP or swollen joint count was found. Logistic regression showed increased odds for having VAS pain ≥39 mm (the median) for a PDQ-score >18 compared to <13 (OR = 10.4; 95%CI 8.6-12.5). CONCLUSIONS: More than 50% of the Danish arthritis patients reported clinically significant pain. More than 20% of the PDQ-completers had indication of neuropathic pain features, which was related to a high pain-level. PDQ-score was associated with DAS28-CRP and VAS pain but not with indicators of peripheral inflammation (CRP and SJC). Thus, pain classification by PDQ may assist in mechanism-based pain treatment.

Non-nociceptive pain in rheumatoid arthritis is frequent and affects disease activity estimation: cross-sectional data from the FRAME study.

BACKGROUND: The painDETECT questionnaire (PDQ) is a mechanism-based pain classification tool assigning patients to one of three categories depending on the quality of the experienced pain. Patients with non-nociceptive pain score high on the PDQ. The objective was to assess the proportions of the three PDQ classification groups in patients with rheumatoid arthritis (RA) and to explore differences in clinical characteristics. METHOD: RA patients initiating or escalating their RA therapy were included prospectively and underwent a thorough examination programme. Low (PDQ score < 13), medium (PDQ score 13-18), and high (PDQ score > 18) scores indicate nociceptive, unclear/possible neuropathic, or neuropathic pain mechanisms, respectively. RESULTS: The 102 included patients were classified into the following PDQ classification groups: low = 65%, medium = 23%, and high = 12%. Patients in the medium and high PDQ groups scored worse on indicators of anxiety, depression, disability, mental health-related quality of life, pain, and fatigue. They also had more tender points and an RA disease activity score based on 28 joints (DAS28) where a higher fraction of the composite score pertained to non-inflammatory factors compared to patients in the low PDQ classification group. There were no differences in objective inflammatory indices across groups. Multiple regression analysis demonstrated that the tender joint count (TJC) and the 36-item Short Form Health Survey (SF36) mental component summary (MCS) score were independently associated with the PDQ score. CONCLUSIONS: In patients initiating or intensifying medical treatment for their RA, non-nociceptive pain (PDQ score ≥ 13) is common. In these patients, the pain mechanisms result in increased disease activity scores on a non-inflammatory basis.

The validity of self-rating depression scales in patients with chronic widespread pain: a Rasch analysis of the Major Depression Inventory.

BACKGROUND: Assessment of depression in chronic pain patients by self-rating questionnaires developed and validated for use in normal and/or psychiatric populations is common. The aim of this study was to evaluate the psychometric properties of the Major Depression Inventory (MDI) in a sample of females with chronic widespread pain (CWP). METHOD: A total of 263 females diagnosed with CWP and referred for rehabilitation completed the MDI as part of the baseline evaluation. Rasch analysis was applied to this dataset. Rasch measurement models allow detailed analyses of an instrument's rating scale and further aspects of validity, including fit of individual scale items to a unidimensional model indicating assessment of a single construct (depression), as a prerequisite for measurement. RESULTS: The Rasch analysis revealed substantial problems with the rating scale properties of the MDI and lack of unidimensionality. In contrast to somatic items, MDI items related to depressed mood and negative view of oneself were distributed at the higher end of the item difficulty measurement scale, indicating low endorsement of these items. DISCUSSION: From the perspective of the Rasch measurement model, the MDI demonstrated insufficient psychometric properties when used to identify and quantify severity of depression in a clinical sample of females with CWP. The observed item endorsement pattern indicated that, in this study population, the relatively high depression severity scores primarily pertained to a common core of pain-related somatic symptoms. Careful consideration when interpreting questionnaire-derived scores of depression implemented in research and routine clinical care of patients with chronic pain is warranted.

Correlations between fatigue and disease duration, disease activity, and pain in patients with rheumatoid arthritis: a systematic review.

OBJECTIVES: Rheumatoid arthritis (RA) patients suffer from disabling fatigue but the causes of this condition are unknown. Our aim was to assess which of the variables disease activity, disease duration, and pain is associated with fatigue. METHOD: We conducted a systematic literature search in MEDLINE and EMBASE, followed by selection of studies according to set criteria, data extraction, and statistical analyses of the relationships in RA between fatigue and the following covariates: disease duration, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), the 28-joint Disease Activity Score (DAS28), swollen to tender joint count ratio (STR), and pain. Linear regression analyses of fatigue regressed on each of the six covariates, and a multiple regression analysis where fatigue was regressed on the six covariates through a forward selection procedure was carried out with construction of correlation measures between fatigue and the covariates. RESULTS: A total of 121 studies were included in the analyses, including > 100 000 RA patients. A high level of fatigue was seen even in well-treated patients, demonstrating fatigue as a major problem in RA. Fatigue was found to be positively correlated with pain, CRP, DAS28, and ESR but not with the STR or disease duration, with pain as the overall domineering factor. CONCLUSIONS: Fatigue has a substantial influence on the lives of RA patients, independent of disease duration. Pain is the domineering factor in the experience and degree of fatigue. Disease activity is positively correlated to fatigue but does not contribute substantially when pain is considered. Optimal pain relief is therefore an important part of the treatment to improve fatigue in RA.

Agreement between touch-screen and paper-based patient-reported outcomes for patients with fibromyalgia: a randomized cross-over reproducibility study.

OBJECTIVES: To compare data based on computerized and paper versions of health status questionnaires (HSQs) for sampling patient-reported outcomes (PROs) in patients with fibromyalgia (FM). In addition, to examine associations between patient characteristics (age, education, computer experience) and differences between versions. Finally, to evaluate the acceptability of computer-based questionnaires among patients with FM. METHOD: The study population comprised female patients diagnosed with FM. All patients completed six HSQs: the Fibromyalgia Impact Questionnaire (FIQ), the Major Depression Inventory (MDI), the 36-item Short Form Health Survey (SF-36), the painDETECT questionnaire (PDQ), the Coping Strategies Questionnaire (CSQ), and the Generalized Anxiety Disorder Self-Assessment Questionnaire (GAD-10), both on paper and using a touch screen. One HSQ was tested at a time in a repeated randomized cross-over design. The two versions were completed with a 5-min interval and between each HSQ the participants had a 5-min break. Means, mean differences with 95% confidence intervals (CIs), medians, median differences, and intraclass correlation coefficients (ICCs) were calculated for all HSQs, including relevant subscales. Associations between patient characteristics and differences between versions were explored using Spearman's correlation coefficients. RESULTS: Twenty women, mean age 48.4 years, participated in the study. Except for one item, ICCs between touch-screen and paper versions of the HSQs examined indicated acceptable agreement (ICC = 0.71-0.99). Overall, mean and median differences revealed no differences between versions. No significant associations were observed for patient characteristics. None of the participants preferred paper questionnaires over computerized versions. CONCLUSIONS: The computerized HSQs using a touch screen gave comparable results to answers given on paper and were generally preferred by the participants.

Validity and reliability of 3D US for the detection of erosions in patients with rheumatoid arthritis using MRI as the gold standard.

PURPOSE: To test the reliability and validity of a 3D US erosion score in RA using MRI as the gold standard. MATERIALS AND METHODS: RA patients were examined with 3D US and 3 T MRI over the 2nd and 3rd metacarpophalangeal joints. 3D blocks were evaluated by two investigators. The erosions were estimated according to a semi-quantitative score (SQS) (0 - 3) and a quantitative score (QS) (mm²). MRI was evaluated according to the RAMRIS score. For the estimation of reliability, intra-class correlation coefficients (ICC) were used. Validity was tested using Spearman's rho (rs). The sensitivity and specificity were also calculated. RESULTS: 28 patients with RA were included. The ICC for the inter-observer reliability in the QS was 0.41 and 0.13 for the metacarpal bone and phalangeal bone, respectively, and 0.86 and 0.16, respectively, in the SQS.  The ICC for the intra-observer reliability in the QS was 0.75 and 0.48 for the metacarpal bone and phalangeal bone, respectively, and 0.83 and 0.60, respectively, in the SQS.  The correlation with MRI for the metacarpal bone was significant, with values of 0.73 (p = 0.0001) (SQ) and 0.74 (p = 0.0001) (SQS). For the phalangeal bone, bad correlation was found: 0.28 (p = 0.145) (SQ) and 0.26 (p = 0.57) (SQS). The sensitivity and specificity for the metacarpal bone were 86 % and 85 % respectively. For the phalangeal bone they were 60 % and 97 %, respectively. CONCLUSION: Good inter- and intra-observer reliability and correlation with MRI were seen in the assessment of erosions with 3D US in the metacarpal bone, while the results were low and insignificant for the phalangeal bone, indicating that 3D US still has room for improvement.

Correlations between radiographic assessments and MRI features of knee osteoarthritis--a cross-sectional study.

OBJECTIVES: To assess correlations between Kellgren & Lawrence (KL) gradings, minimum joint space width (mJSW) measurements and the Boston Leeds Osteoarthritis Knee Score (BLOKS) within a cohort of obese patients with knee osteoarthritis (KOA). METHODS: 192 Participants were recruited from an outpatient clinic (ClinicalTrials.gov: NCT00655941). Inclusion criteria were age ≥50 years, body mass index (BMI) ≥30 kg/m(2) plus symptomatic and verified KOA. 1.5 T magnetic resonance imaging (MRI) scans were assessed using BLOKS and bi-plane radiography by mJSW and KL. Statistics used were Spearman rank correlation coefficients. RESULTS: The average patient was 63 years of age, female and had a BMI of 37. KL gradings correlated to cartilage damage, bone marrow lesions and meniscus pathology (r = 0.15-0.76) and similar results were found for the relationship between BLOKS and mJSW. BLOKS assessed knee joint pathology co-segregated with compartment and grade specific KL (P < 0.0001). BLOKS variables were statistically significant correlated, particularly in the medial tibiofemoral compartment (r = 0.42-0.80). Adjusting for age, gender and BMI did not alter these associations. CONCLUSION: Extensive pathological damage is present even in mild radiographic KOA and BLOKS gradings and KL scores increase together. Analyses of compartment specific KL scores revealed differences in their relationship to the assessed MRI variables. Our study displays the segregation of MRI gradings with respect to location and level of radiographic scores, reveals a high inter-dependency of MRI-assessed structures, and describes some redundancy of specific BLOKS variables.

Weight loss is effective for symptomatic relief in obese subjects with knee osteoarthritis independently of joint damage severity assessed by high-field MRI and radiography.

OBJECTIVE: With an increasing prevalence of older and obese citizens, the problems of knee osteoarthritis (KOA) will escalate. Weight loss is recommended for obese KOA patients and in a majority of cases this leads to symptomatic relief. We hypothesized that pre-treatment structural status of the knee joint, assessed by radiographs, 1.5 T magnetic resonance imaging (MRI) and knee-joint alignment, may influence the symptomatic changes following a significant weight reduction. DESIGN: Patients were recruited from a Department of Rheumatology. Eligibility criteria were age above 50 years, body mass index ≥ 30 kg/m(2), primary KOA diagnosed according to the American College of Rheumatology (ACR) criteria and having verified structural damage. Patients underwent a 16 weeks dietary programme with formula products and counselling. MRI and radiographs of the most symptomatic knee were obtained at baseline and assessed for structural damage using the Boston-Leeds Osteoarthritis of the Knee Score, minimum joint space width and Kellgren-Lawrence score. Imaging variables, muscle strength and degree of alignment, were examined as predictors of changes in Knee Osteoarthritis Outcome Score (KOOS) and Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) - Osteoarthritis Research Society International (OARSI) Responder Criterion. RESULTS: Structural damage at baseline assessed by imaging, muscle strength or knee-joint alignment showed no statistically significant association to changes in KOOS pain and function in daily living (r ≤ 0.13; P>0.05) or the OMERACT-OARSI Responder Criterion (OR 0.48-1.68; P-values ≥ 0.13). CONCLUSIONS: Presence of joint damage did not preclude symptomatic relief following a clinically relevant weight loss in older obese patients with KOA. Neither muscle strength nor knee-joint alignment was associated with the degree of symptomatic relief.

Descending pain modulation and its interaction with peripheral sensitization following sustained isometric muscle contraction in fibromyalgia.

OBJECTIVE: Sustained isometric muscle contraction (fatiguing contraction) recruits segmental and/or extrasegmental descending inhibition in healthy subjects but not in fibromyalgia (FM). We hypothesized that fatiguing contraction may shift descending pain modulation from inhibition towards facilitation and that the effect of descending pain modulation be dependent on peripheral muscle pain sensitivity. METHODS: Pressure pain thresholds (PPT) were measured from 13 points bilaterally in the upper trapezius muscle and from the mid-point bilaterally in the tibialis anterior before-, immediately after-, and 20 min after fatiguing contraction of shoulder abduction in 22 FM patients and 22 matched healthy controls. Rate of fatigue, pain intensity, and the duration of fatiguing contraction were recorded. RESULTS: The duration of fatiguing contraction was significantly shorter in FM (132.4 ± 25.2 s) than healthy control groups (286.2 ± 24.1 s) (P < 0.05), pain intensity was significantly higher in FM (8.25 ± 0.8 cm) than in healthy controls (5.1 ± 0.65 cm) (P < 0.01), whereas both groups reported similar fatigue intensity (P > 0.05). Following the contraction, PPTs were increased significantly and heterogeneously in the upper trapezius over time, but not, in the tibialis anterior muscle in healthy controls. However, PPT were significantly decreased over time in the tibialis anterior (P < 0.05), but not, in the upper trapezius in FM. CONCLUSIONS: Descending pain modulation shifts from descending inhibition towards descending facilitation following muscle nociception in FM. Peripheral mechanical hyperalgesia and descending facilitation counterbalance the effect of descending inhibition in FM.

Differences between questionnaire- and interview-based measures of activities of daily living (ADL) ability and their association with observed ADL ability in women with rheumatoid arthritis, knee osteoarthritis, and fibromyalgia.

OBJECTIVES: Although self-report based on questionnaire is the common method to obtain information about activities of daily living (ADL) ability in rheumatic diseases, little is known about the relationship between measures of ADL ability based on questionnaire, interview, and observation. The present study examined whether measures of self-reported ADL ability based on questionnaire and interview yielded different results, determined whether the magnitude of the difference varied among women with rheumatoid arthritis (RA), knee osteoarthritis (OA), and fibromyalgia (FM), and investigated the relationships between self-reported and observed ADL ability. METHOD: The 47 ADL tasks of the ADL taxonomy were used to evaluate self-reported ADL ability based on questionnaire (ADL-Q) and interview (ADL-I), and the Assessment of Motor and Process Skills (AMPS) was used to obtain measures of observed ADL ability. RESULTS: Participants across diagnostic groups reported significantly more ADL ability based on the ADL-Q than on the ADL-I. Moderate correlations were found between the ADL-Q and ADL-I ability measures. Although low to moderate correlations were seen between measures based on the AMPS ADL motor scale and the ADL-Q and ADL-I, respectively, correlations between measures based on AMPS ADL process scale and ADL-Q and ADL-I were generally low. Overall, there was no difference in how the measures based on the two modes of self-report related to the observed ADL ability measures. CONCLUSION: Measures of self-reported ADL ability based on either questionnaire or interview have limited relationship to each other or to observed performance of ADL tasks.

Ultrasound Doppler score correlates with OMERACT RAMRIS bone marrow oedema and synovitis score in the wrist joint of patients with rheumatoid arthritis.

PURPOSE: MRI is considered the standard of reference for advanced imaging in rheumatoid arthritis (RA). However, in daily clinical practice ultrasound (US) imaging with Doppler information is more versatile and often used for fast and dynamic assessment of joint inflammation. The aim was to compare low-field MRI scores with the US Doppler measurements in the wrist joint of patients with RA. MATERIAL AND METHODS: Fifty consecutive patients with RA (46 women & 4 men) completed both low-field dedicated extremity MRI (E-scan®, Esaote) and a high-end US (Sequioa®, Siemens) imaging of the wrist before initiating either biological treatment (n = 26) or intraarticular injection of Depomedrole® (n = 24). Mean age was 56 years (range 21 - 83 years); mean disease duration 87.2 months (range 4 - 349 months), mean DAS 28 4,8 (range 2 - 7). MRI was scored according to the OMERACT RAMRIS recommendations and US Doppler colour-fractions were determined. RESULTS: Using Spearman's rho, we found a relatively good to moderate correlation between the US colour-fraction and the total OMERACT bone marrow oedema and synovitis scores on MRI (r = 0.6; p < 0.001 and r = 0.4; p < 0.006 respectively). There was a trend but no significant correlation with the total OMERACT erosion score (r = 0.3; p = 0.06). CONCLUSION: Within limits, the OMERACT RAMRIS scores of inflammation in RA patients (bone marrow oedema and synovial enhancement) are comparable to the US colour-fraction measurements using a high-end US scanner. Both imaging modalities detect inflammation although showing different aspects of the inflammatory process in the wrist joint. The higher correlation between US colour-fractions and MRI bone marrow oedema indicates a potential importance of US Doppler in monitoring inflammatory disease changes in RA.

The number needed to treat for second-generation biologics when treating established rheumatoid arthritis: a systematic quantitative review of randomized controlled trials.

OBJECTIVE: To evaluate the number needed to treat (NNT) and the number needed to harm (NNH) of the second-generation biologics abatacept, certolizumab, golimumab, rituximab, and tocilizumab in patients with established rheumatoid arthritis (RA) taking concomitant methotrexate (MTX). METHODS: A systematic literature search of MEDLINE, EMBASE, Web of Science, and the Cochrane Register of Controlled Trials was conducted up to 1 November 2009. We selected any published randomized, double-blind, MTX-controlled study including RA patients with a mean disease duration of at least 5 years before entering a pivotal trial on second-generation biological therapy. Studies eligible for inclusion involved patients, who had previously shown inadequate response to conventional disease-modifying anti-rheumatic drug (DMARD) therapy. Pre-specified binary outcomes were extracted with a preference for 1-year data (6-month data were used if no data were available for 1 year). Two reviewers independently extracted the data necessary to estimate the absolute measures in a non-responder intention-to-treat (ITT) analysis. RESULTS: Five randomized controlled trials, one for each of the drugs, were selected and data extracted according to published data at endpoint for American College of Rheumatology 50% (ACR50)-responding patients, and withdrawals due to adverse events. NNT ranged from four to six treated patients to achieve one ACR50 response, while withdrawals due to adverse events were few and non-significant compared to the placebo group, except for rituximab administered as 1000 mg. CONCLUSION: Comparable efficacy was shown by the five biological agents studied, with few adverse events. However, for rituximab, tocilizumab, and golimumab, only 6-month data were available, hampering the external validity with regard to long-term efficacy and tolerability. A low dose (500 mg) of rituximab may be as effective as the recommended dose of 1000 mg.

Expression of full-length and splice forms of FoxP3 in rheumatoid arthritis.

OBJECTIVE: The aim of our study was to compare the presence of full-length and alternative splice forms of FoxP3 mRNA in CD4 cells from rheumatoid arthritis (RA) patients and healthy controls. METHODS: A quantitative real-time polymerase chain reaction (QRT-PCR) method was used to measure the amount of FoxP3 mRNA full-length and splice forms. CD4-positive T cells were isolated from peripheral blood from 50 RA patients by immunomagnetic separation, and the FoxP3 mRNA expression was compared with the results from 10 healthy controls. RESULTS: We observed an increased expression of full-length FoxP3 mRNA in RA patients when compared to healthy controls, as well as an increase in CD25 mRNA expression, but no corresponding increase in CTLA-4 mRNA expression. The presence of an alternative splice form of FoxP3 lacking exon 2 was confirmed in both RA patients and healthy controls, but with no significant difference in expression between the two groups. There was a positive correlation between the amount of FoxP3 mRNA and the clinical inflammation parameters C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), and a negative correlation between FoxP3 mRNA and the dose of methotrexate (MTX) given to the patients. CONCLUSION: RA patients express more full-length FoxP3 than healthy controls in peripheral blood CD4-positive cells, suggesting an increased number of regulatory T cells (Tregs). However, no concomitant increase in CTLA-4 expression was seen. We therefore propose that the Tregs are left unable to suppress the ongoing inflammation due to a deficiency in CTLA-4 needed for cell contact-dependent suppression.

Isokinetic and isometric muscle strength in a healthy population with special reference to age and gender.

AIM: Muscle strength is an excellent indicator of general health when based on reliable measurements. Muscle strength data for a healthy population are rare or non-existent. The aim of the present study was to measure a set of normal values for isometric and isokinetic muscle strength for all the major joint movements of the body and, from these data, to create a basis for comparison of the muscle strength of an individual with the expected value in a normal population. METHODS: A randomly selected group, aged 20-80 years, from the Copenhagen City Heart Study were studied. The group was subgrouped according to age and gender. Isometric and isokinetic muscle strength was measured in each subject across the main joints in the body. A statistical model was developed that encompassed the three main muscle groups: upper limbs, trunk and lower limbs. RESULTS: Muscle strength in healthy men decreases in a linear fashion from the age of 25 years down to between 54% and 89% at the age of 75 years, and seems not highly dependent on any other parameter than age. For women, the muscle strength is dependent on weight and is only related to age from around 40 years of age. The decrease in muscle strength from the age around 40 to 75 years is 48-92%. For most muscle groups, men are 1.5-2 times stronger than women, with the oldest men having strength similar to that observed among the youngest women. CONCLUSION: We developed a model to compare the isometric and isokinetic muscle strength of all the major joint movements of an individual with values for a healthy man or woman at any age in the range of 20-80 years. In all age groups, women have lower muscle strength than men. Men's muscle strength declines with age, while women's muscle strength declines from the age of 41 years.

Ultrasound colour Doppler measurements in a single joint as measure of disease activity in patients with rheumatoid arthritis--assessment of concurrent validity.

OBJECTIVE: Colour Doppler ultrasound (CDU) displays blood flow in the tissues and is able to detect hyperaemia. Because hyperaemia is part of the inflammatory response, the amount of CDU activity in the inflamed synovium may be used to quantify the inflammatory activity in RA. It has never been investigated if the amount of CDU activity in a single joint can be used to quantify disease activity in RA. METHODS: A total of 109 patients with RA and affection of the wrist joint underwent a standardized CDU examination assessing three positions in their most affected wrist at start up in biological treatment. On the same day the following measures of disease activity were collected: assessment of the number of tender and swollen joints, CRP, ESR and 28-joint disease activity score (DAS28). The amount of CDU activity was quantified by measuring the percentage of colour in the synovium--the colour fraction (CF). Correlation between CF and other measures of disease activity was calculated. RESULTS: There was a significant correlation between CF and DAS28 (r = 0.29; P < 0.001), swollen joint count (r = 0.35; P < 0.001), CRP (r = 0.5; P < 0.001) and ESR (r = 0.5; P < 0.001). No other significant correlations were found. CONCLUSION: A standardized ultrasound examination of a single affected wrist joint in patients with RA may be used as a measure of disease activity. More studies are needed to identify the number of joints needed to examine by CDU to obtain the best validity of Doppler measurements.

Quantification of colour Doppler activity in the wrist in patients with rheumatoid arthritis--the reliability of different methods for image selection and evaluation.

PURPOSE: The amount of colour Doppler activity in the inflamed synovium is used to quantify inflammatory activity. The measurements may vary due to image selection, quantification method, and point in cardiac cycle. This study investigated the test-retest reliability of ultrasound colour Doppler measurements in the wrist of patients with rheumatoid arthritis (RA) using different selection and quantification methods. MATERIALS AND METHODS: 14 patients with RA had their wrist scanned twice by the same investigator with an interval of 30 minutes. The images for analysis were selected either by the anatomical position only or by the anatomical position with maximum colour Doppler activity. Subsequently, the amount of colour Doppler was measured in an area defined by either the synovial tissue or by specific anatomical structures surrounding the synovial tissue. RESULTS: The best test-retest reliability was obtained when the images were selected guided by colour Doppler and the subsequent quantification was done in an area defined by anatomical structures. With this method, the intra-class coefficient ICC (2.1) was 0.95 and the within-subject SD (SW) was 0.017, indicating good reliability. In contrast, poor test-retest reliability was found if the images were selected by anatomical position only and the quantification was done in an area defined by the synovial tissue (ICC [2.1] = 0.48 and SW = 0.049). CONCLUSION: The study showed that colour Doppler measurements are reliable if the images for analysis are selected by anatomical position in combination with colour Doppler activity and the subsequent analysis is performed in an area defined by anatomical structures.

Movement detection impaired in patients with knee osteoarthritis compared to healthy controls: a cross-sectional case-control study.

The purpose of this study was to clarify whether osteoarthritis (OA) patients have a localized or a generalized reduction in proprioception. Twenty one women with knee OA (mean age [SD]: 57.1 [12.0] years) and 29 healthy women (mean age [SD]: 55.3 [10.1] years) had their joint position sense (JPS) and threshold to detection of a passive movement (TDPM) measured in both knees and elbows. JPS was measured as the participant's ability to actively reproduce the position of the elbow and knee joints. TDPM was measured as the participant's ability to recognize a passive motion of the elbow and knee joints. The absolute error (AE) for JPS (i.e., absolute difference in degrees between target and estimated position) and for TDPM (i.e., the difference in degrees at movement start and response when recognizing the movement) was calculated. For TDPM a higher AE (mean [SE]) was found in the involved knees in patients than in the matched knees of healthy participants (AE: 2.41 degrees [0.20 degrees] versus 1.47 degrees [0.14], p=0.001). The same held true for the non-involved knees between OA and healthy subjects (AE: 2.20 degrees [0.20 degrees] versus 1.57 degrees [0.14 degrees], p=0.016). Furthermore TDPM was higher in OA patients' right elbows compared to healthy participants' right elbows (AE: 2.15 degrees [0.20 degrees] versus 1.45 degrees [0.15 degrees], p=0.011). No significant difference between healthy women and OA patients regarding the left elbow for TDPM, or JPS was observed. The present age-controlled, cross-sectional study suggests that there is an increase in threshold to detection of a passive motion in knees and elbows for patients with knee OA. This indicates that OA may be associated with a generalized defect in proprioception with possible implications for the pathogenesis of the joint degeneration.

EULAR evidence-based recommendations for the management of fibromyalgia syndrome.

OBJECTIVE: To develop evidence-based recommendations for the management of fibromyalgia syndrome. METHODS: A multidisciplinary task force was formed representing 11 European countries. The design of the study, including search strategy, participants, interventions, outcome measures, data collection and analytical method, was defined at the outset. A systematic review was undertaken with the keywords "fibromyalgia", "treatment or management" and "trial". Studies were excluded if they did not utilise the American College of Rheumatology classification criteria, were not clinical trials, or included patients with chronic fatigue syndrome or myalgic encephalomyelitis. Primary outcome measures were change in pain assessed by visual analogue scale and fibromyalgia impact questionnaire. The quality of the studies was categorised based on randomisation, blinding and allocation concealment. Only the highest quality studies were used to base recommendations on. When there was insufficient evidence from the literature, a Delphi process was used to provide basis for recommendation. RESULTS: 146 studies were eligible for the review. 39 pharmacological intervention studies and 59 non-pharmacological were included in the final recommendation summary tables once those of a lower quality or with insufficient data were separated. The categories of treatment identified were antidepressants, analgesics, and "other pharmacological" and exercise, cognitive behavioural therapy, education, dietary interventions and "other non-pharmacological". In many studies sample size was small and the quality of the study was insufficient for strong recommendations to be made. CONCLUSIONS: Nine recommendations for the management of fibromyalgia syndrome were developed using a systematic review and expert consensus.

The number needed to treat for adalimumab, etanercept, and infliximab based on ACR50 response in three randomized controlled trials on established rheumatoid arthritis: a systematic literature review.

OBJECTIVE: To compare the efficacy of adalimumab, etanercept, and infliximab in patients with established rheumatoid arthritis (RA) taking concomitant methotrexate (MTX) by calculating the number needed to treat (NNT) using three different methods. METHODS: A systematic literature search of the Cochrane Library, MEDLINE, and EMBASE was conducted from inception to 30 June 2006. Two pairs of investigators, a Danish and a Swedish pair, independently conducted a structured literature review. The reviewers selected any published randomized, double-blind, MTX controlled study of adalimumab, etanercept, and infliximab, presenting the American College of Rheumatology 50% response (ACR50) after 12 months in RA patients with a mean disease duration of at least 5 years. The two review groups independently extracted the estimates necessary to calculate the NNT. RESULTS: The reviewers consistently selected the same three randomized, controlled trials (RCTs), one for each of the drugs, and extracted equal data for the number of patients completing the 12-month intervention, and the corresponding number of ACR50 responding patients after therapy. Some baseline differences were noted: patients in the etanercept trial had a shorter disease duration and did not receive MTX prior to inclusion; patients in the adalimumab study had lower Health Assessment Questionnaire (HAQ) scores. The calculated NNTs varied slightly depending on the method used. The fully adjusted NNTs (95% confidence intervals) for adalimumab, etanercept, infliximab standard dosage and infliximab double dosage were 4 (3-6), 4 (3-6), 8 (4-66), and 4 (3-11) patients, respectively. CONCLUSION: This study indicates equal efficacy of the three anti-tumour necrosis factor (TNF) therapies.