The benefit of adding a physiotherapy or occupational therapy intervention programme to a standardized group-based interdisciplinary rehabilitation programme for patients with chronic widespread pain: a randomized active-controlled non-blinded trial.

OBJECTIVE: To evaluate the benefit of adding occupational therapy or physiotherapy interventions to a standard rehabilitation programme targeted for chronic widespread pain. DESIGN: Randomized active-controlled non-blinded trial. SUBJECTS: Women with chronic widespread pain recruited in a tertiary outpatient clinic. METHODS: Participants were randomized to a two-week, group-based standard rehabilitation programme followed by 16 weeks of group-based occupational therapy (Group BOT, n = 43) or 16 weeks of group-based physiotherapy (Group BPT, n = 42). Group A only received the two-week rehabilitation programme acting as comparator (n = 96). OUTCOMES: Primary outcomes were the Assessment of Motor and Process Skills and Short Form-36 (SF36) Mental Component Summary score. RESULTS: Mean changes in motor and process ability measures were clinically and statistically insignificant and without differences across the three groups assessed 88 weeks from baseline. Motor ability measures: -0.006 (95% confidence interval (CI): -0.244 to 0.233) in Group BOT; -0.045 (95% CI: -0.291 to 0.202) in Group BPT; and -0.017 (95% CI: -0.248 to 0.213) in Group A, P = 0.903. Process ability measures: 0.087 (95% CI: -0.056 to 0.231) in Group BOT; 0.075 (95% CI: -0.075 to 0.226) in Group BPT; and 0.072 (95% CI: -0.067 to 0.211) in Group A, P = 0.924. Mean changes in patient-reported outcomes were likewise small; clinically and statistically insignificant; and independent of group allocation, except for the SF36 mental component summary score in the BPT group: 8.58 (95% CI: 1.75 to 15.41). CONCLUSION: Participants were on average stable in observation-based measures of functional ability and patient-reported outcomes, except in overall mental well-being, favouring the enhanced intervention. Efficacy of additional interventions on functional ability remains uncertain.

Psychometric properties of the painDETECT questionnaire in rheumatoid arthritis, psoriatic arthritis and spondyloarthritis: Rasch analysis and test-retest reliability.

BACKGROUND: Pain is inherent in rheumatoid arthritis (RA), psoriatic arthritis (PsA) and spondyloarthritis (SpA) and traditionally considered to be of nociceptive origin. Emerging data suggest a potential role of augmented central pain mechanisms in subsets of patients, thus, valid instruments that can identify underlying pain mechanisms are needed. The painDETECT questionnaire (PDQ) was originally designed to differentiate between pain phenotypes. The objectives were to evaluate the psychometric properties of the PDQ in patients with inflammatory arthritis by applying Rasch analysis and to explore the reliability of pain classification by test-retest. METHODS: For the Rasch analysis 900 questionnaires from patients with RA, PsA and SpA (300 per diagnosis) were extracted from 'the DANBIO painDETECT study'. The analysis was directed at the seven items assessing somatosensory symptoms and included: 1) the performance of the six-category Likert scale; 2) whether a unidimensional construct was defined; 3) the reliability and precision of estimates. Another group of 30 patients diagnosed with RA, PsA or SpA participated in a test-retest study. Intraclass Correlation Coefficients (ICC) and classification consistency were calculated. RESULTS: The Rasch analysis revealed: (1) Acceptable psychometric rating scale properties; the frequency distribution peaked in category 0 except for item 5, threshold calibration >10 observations per category, no disorder in the category measures for all items, scale category outfit Mnsq <2.0, small distances (<1.4 logits) between thresholds for category 1, 2 and 3 for all items. (2) The principal component analysis supported unidimensionality; the standardized residuals showed that 53.7% of total variance was explained by the measure and the magnitude of first contrast had an eigenvalue of 1.5, no misfitting items, clinical insignificant different item hierarchies across diagnoses (DIF < 0.5 logits). (3) A targeted item-person map, person and item separation indices of 1.88(reliability = 0.78), and 13.04 (reliability = 0.99). The test-retest revealed: ICC: RA 0.86(0.56-0.96), PsA 0.96(0.74-0.99), SpA 0.93(0.76-98), overall 0.94(0.84-0.98). Classification consistency was: RA 70%, PsA 80%, SpA 90%, overall 80%. CONCLUSION: The results support that the PDQ can be used as a classification instrument and assist identification of underlying pain-mechanisms in patients suffering from inflammatory arthritis.

Reliability of Pain Measurements Using Computerized Cuff Algometry: A DoloCuff Reliability and Agreement Study.

INTRODUCTION: Computerized pneumatic cuff pressure algometry (CPA) using the DoloCuff is a new method for pain assessment. Intra- and inter-rater reliabilities have not yet been established. Our aim was to examine the inter- and intrarater reliabilities of DoloCuff measures in healthy subjects. METHODS: Twenty healthy subjects (ages 20 to 29 years) were assessed three times at 24-hour intervals by two trained raters. Inter-rater reliability was established based on the first and second assessments, whereas intrarater reliability was based on the second and third assessments. Subjects were randomized 1:1 to first assessment at either rater 1 or rater 2. The variables of interest were pressure pain threshold (PT), pressure pain tolerance (PTol), and temporal summation index (TSI). Reliability was estimated by a two-way mixed intraclass correlation coefficient (ICC) absolute agreement analysis. Reliability was considered excellent if ICC > 0.75, fair to good if 0.4 < ICC < 0.75, and poor if ICC < 0.4. Bias and random errors between raters and assessments were evaluated using 95% confidence interval (CI) and Bland-Altman plots. RESULTS: Inter-rater reliability for PT, PTol, and TSI was 0.88 (95% CI: 0.69 to 0.95), 0.86 (95% CI: 0.65 to 0.95), and 0.81 (95% CI: 0.42 to 0.94), respectively. The intrarater reliability for PT, PTol, and TSI was 0.81 (95% CI: 0.53 to 0.92), 0.89 (95% CI: 0.74 to 0.96), and 0.75 (95% CI: 0.28 to 0.91), respectively. CONCLUSION: Inter-rater reliability was excellent for PT, PTol, and TSI. Similarly, the intrarater reliability for PT and PTol was excellent, while borderline excellent/good for TSI. Therefore, the DoloCuff can be used to obtain reliable measures of pressure pain parameters in healthy subjects.

Ultrasound Doppler but not temporal summation of pain predicts DAS28 response in rheumatoid arthritis: a prospective cohort study.

OBJECTIVE: Previous studies have suggested a link between inflammation and central sensitization of pain in patients with RA. We conducted a prospective cohort study to determine whether US Doppler (USD), temporal summation (TS) of pain-assessed at baseline-and the potential interaction between them could predict the treatment response in RA. METHODS: Patients were recruited from Departments of Rheumatology in the Copenhagen area and from private clinics. RA patients, who were scheduled to initiate therapy with either a conventional synthetic DMARD (csDMARD; including DMARD-naïve patients) or a biologic DMARD (bDMARD) agent (including bDMARD switch), were included and examined before the start of treatment and after 4 months. During the 4 months, patients received routine care from their treating rheumatologist. RESULTS: Multiple regression analysis was conducted, with change in DAS28 as the dependent variable. In unadjusted models, baseline USD score was significantly associated with DAS28 (ß = 0.06; 95% CI: 0.02, 0.09; P < 0.001), whereas TS and their interaction were not. After adjusting for age, sex, disease duration, baseline DAS28 and whether patients initiated a csDMARD or a bDMARD, the USD score was still significantly associated with change in DAS28 (ß = 0.032; 95% CI: 0.001, 0.064; P = 0.046), whereas TS remained insignificant. CONCLUSION: USD assessed at baseline is valuable as a prognostic factor for change in disease activity in 'real-life' RA patients. We did not find evidence to suggest that TS or the interaction between USD and TS was prognostically important for this group of patients.

Aquatic exercise for the treatment of knee and hip osteoarthritis.

BACKGROUND: Osteoarthritis is a chronic disease characterized by joint pain, tenderness, and limitation of movement. At present, no cure is available. Thus only treatment of the person's symptoms and treatment to prevent further development of the disease are possible. Clinical trials indicate that aquatic exercise may have advantages for people with osteoarthritis. This is an update of a published Cochrane review. OBJECTIVES: To evaluate the effects of aquatic exercise for people with knee or hip osteoarthritis, or both, compared to no intervention. SEARCH METHODS: We searched the following databases up to 28 April 2015: the Cochrane Central Register of Controlled Trials (CENTRAL; the Cochrane Library Issue 1, 2014), MEDLINE (from 1949), EMBASE (from 1980), CINAHL (from 1982), PEDro (Physiotherapy Evidence Database), and Web of Science (from 1945). There was no language restriction. SELECTION CRITERIA: Randomized controlled clinical trials of aquatic exercise compared to a control group (e.g. usual care, education, social attention, telephone call, waiting list for surgery) of participants with knee or hip osteoarthritis. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion, extracted data and assessed risk of bias of the included trials. We analysed the pooled results using standardized mean difference (SMD) values. MAIN RESULTS: Nine new trials met the inclusion criteria and we excluded two earlier included trials. Thus the number of participants increased from 800 to 1190 and the number of included trials increased from six to 13. Most participants were female (75%), with an average age of 68 years and a body mass index (BMI) of 29.4. Osteoarthritis duration was 6.7 years, with a great variation of the included participants. The mean aquatic exercise duration was 12 weeks. We found 12 trials at low to unclear risk of bias for all domains except blinding of participants and personnel. They showed that aquatic exercise caused a small short term improvement compared to control in pain (SMD -0.31, 95% CI -0.47 to -0.15; 12 trials, 1076 participants) and disability (SMD -0.32, 95% CI -0.47 to -0.17; 12 trials, 1059 participants). Ten trials showed a small effect on quality of life (QoL) (SMD -0.25, 95% CI -0.49 to -0.01; 10 trials, 971 participants). These effects on pain and disability correspond to a five point lower (95% CI three to eight points lower) score on mean pain and mean disability compared to the control group (scale 0 to 100), and a seven point higher (95% CI 0 to 13 points higher) score on mean QoL compared with control group (scale 0 to 100). No included trials performed a radiographic evaluation. No serious adverse events were reported in the included trials with relation to aquatic exercise. AUTHORS' CONCLUSIONS: There is moderate quality evidence that aquatic exercise may have small, short-term, and clinically relevant effects on patient-reported pain, disability, and QoL in people with knee and hip OA. The conclusions of this review update does not change those of the previous published version of this Cochrane review.

Ultrasound colour Doppler is associated with synovial pathology in biopsies from hand joints in rheumatoid arthritis patients: a cross-sectional study.

OBJECTIVES: Little is known regarding the association between ultrasound-determined pathological synovial blood flow and synovial pathology in rheumatoid arthritis (RA). We therefore examined the association between colour Doppler ultrasound imaging and synovitis assessed by histopathology and specific cell markers by immunohistochemistry in patients with RA. METHODS: 81 synovial sites from wrist and finger joints from 29 RA patients were evaluated by ultrasound colour Doppler and subsequently biopsied by needle arthroscopy. The association between ultrasound colour fraction and an overall synovitis score and immunohistochemical staining for CD3, CD68, Ki67 and von Willebrand factor was investigated, including repeated samples from the same patients. The overall synovitis score (total 0-9) assessed synovial lining hyperplasia (0-3), stromal activation (0-3) and inflammatory infiltration (0-3). Data were clustered within patients, thus a linear mixed model was applied for the statistical tests. Parsimony in the statistical models was achieved omitting covariates from the model in the case of what was judged no statistical significance (p>0.1). RESULTS: Doppler colour fraction showed an association with the overall synovitis score (approximated Spearman, approximately r=0.43, p=0.003). The density of all immunohistochemical stainings showed a significant association with Doppler colour fraction: von Willebrand factor (approximately r=0.44, p=0.01), CD68 (approximately r=0.53, p=0.02), Ki67 (approximately r=0.57, p=0.05) and CD3 (approximately r=0.57, p=0.0003). CONCLUSIONS: Colour Doppler activity is associated with the extent of inflammation present in the synovial biopsies from RA patients. However, synovial pathology was also seen in biopsies taken from Doppler negative sites.

Muscle fatigue in fibromyalgia is in the brain, not in the muscles: a case-control study of perceived versus objective muscle fatigue.

OBJECTIVE: To investigate relationships between perceived and objectively measured muscle fatigue during exhausting muscle contractions in women with fibromyalgia (FM) compared with healthy controls (HC). METHODS: Women with FM and HC completed an isometric muscle exhaustion task at 90° shoulder abduction. Surface electromyographic (EMG) activity in the deltoid muscle was recorded together with self-reported level of muscle fatigue. RESULTS: 25 participants with FM and 23 HC were included. Average time to exhaustion was 254 s shorter in participants with FM than in HC. Participants with FM did not exhibit the same level of objective signs of muscle fatigue, seen as fewer changes in the EMG activity, as the HC during the exhaustion task. The task did not provoke pain in the HC, while participants with FM reported a doubling of pain. CONCLUSIONS: Women with FM had shorter exhaustion times and showed fewer objective signs of muscle fatigue during an exhausting isometric shoulder abduction compared with younger HC. This indicates that perceived muscle fatigue may be of central origin and supports the notion of central nervous dysfunction as basic pathological changes in FM.

Changes in lower extremity muscle mass and muscle strength after weight loss in obese patients with knee osteoarthritis: a prospective cohort study.

OBJECTIVE: To investigate the effects of low-energy diet-induced weight loss on lower-extremity muscle mass and knee muscle strength in obese patients with knee osteoarthritis (OA), and the associations of these effects. METHODS: We studied 159 obese patients with knee OA and available data from body composition analysis that had been performed using dual x-ray absorptiometry scanning and isometric muscle strength testing of the knee in extension and in flexion. The data had been obtained as part of a randomized controlled trial, with measurements performed before and after a supervised low-energy diet-induced weight loss intervention lasting 16 weeks. RESULTS: The patients lost an average of 12.9 kg (95% confidence interval [95% CI] 10.2, 15.7) (13% of baseline weight). The weight loss consisted of 10.9 kg fat mass (95% CI 8.9, 12.9), of which 3.8 kg (95% CI 2.7, 4.9) was leg fat mass. Total lean body mass was reduced by 1.9 kg (95% CI 0.05, 3.8), of which 0.785 kg (95% CI 0.09, 1.476) was leg lean mass. Absolute muscle strength decreased by ∼3-4% after the weight loss, whereas body mass-normalized muscle strength increased by 11-12%. At baseline, leg lean mass was significantly related to muscle strength, but changes in these measurements at followup were not related. CONCLUSION: Weight loss induced by a low-energy diet led to independent losses of leg muscle tissue and strength. The weight loss was accompanied by increased normalized muscle strength along with improved self-reported disability and pain--all of which are beneficial to patients with knee OA. The present results suggest that significant weight loss in patients with knee OA should be followed by an exercise regimen to restore or increase muscle mass.

Effect of nonsteroidal antiinflammatory drugs on the C-reactive protein level in rheumatoid arthritis: a meta-analysis of randomized controlled trials.

OBJECTIVE: To evaluate the effects of oral nonsteroidal antiinflammatory drugs (NSAIDs) on C-reactive protein (CRP) levels in rheumatoid arthritis (RA) patients, with a prespecified focus on the different NSAIDs. METHODS: We performed a systematic search in Medline via PubMed, the Cochrane Central Register of Controlled Trials, EMBase via OVID, the Institute for Scientific Information Web of Science, and other sources. Eligible trials were parallel-group, randomized, placebo-controlled trials of oral NSAID therapy in RA patients for which there were extractable CRP data. Standardized mean differences (SMDs) with 95% confidence intervals (95% CIs) were calculated from the differences in means of CRP levels between groups (active treatment minus placebo) divided by the pooled SDs. For the meta-analysis, a random-effects model was used to estimate the overall change in CRP level, and stratified analysis was used to examine differences among NSAIDs. RESULTS: We included 19 trials of 10 different NSAIDs. Overall, NSAIDs showed no effect on the CRP level (SMD 0.01 [95% CI -0.03, 0.06], P = 0.62). However, the prespecified stratified analysis indicated varying effects on the CRP level according to the different NSAIDs; lumiracoxib caused a statistically significant and consistent (I(2) = 0%) increase in the CRP level (SMD 0.13 [95% CI 0.01, 0.25], P = 0.037), whereas naproxen caused a statistically significant and consistent (I(2) = 0%) decrease in the CRP level (SMD -0.11 [95% CI -0.20, -0.02], P = 0.022). CONCLUSION: Overall, NSAIDs have no effect on the CRP level. However, the nonselective NSAID naproxen was associated with a significant decrease in the CRP level, whereas the cyclooxygenase 2-selective NSAID lumiracoxib was associated with a significant increase in the CRP level. This finding is interesting considering the suspected influence of NSAIDs on cardiovascular complications.

Assessment of pressure-pain thresholds and central sensitization of pain in lateral epicondylalgia.

OBJECTIVE.: To assess pain sensitivity and spreading hyperalgesia in lateral epicondylalgia (LE). SUBJECTS.: Twenty-two women with LE, and 38 controls were included. OUTCOME MEASURES.: Computerized cuff pressure algometry was used for assessment of pressure-pain threshold and tolerance. The stimulus was applied using a single (stimulation-area: 241 cm(2) ) or double-chambered (stimulation-area: 482 cm(2) ) tourniquet on the arm and leg. Spatial summation was expressed as the ratio between pressure-pain thresholds to single and double cuff-chamber stimulation. During 10-minute constant pressure stimulation at intensity relative to the individual pain threshold, the pain intensity was continuously recorded using an electronic visual analogue scale (VAS), and from this the degree of temporal summation was estimated. For LE, a Doppler ultrasound examination of the elbow was made to identify inflammation. RESULTS.: In LE compared with controls the pressure-pain threshold and tolerance were on average reduced by respectively 31% (nonsignificant) and 18% (nonsignificant) on the lower arm and by 32% (P < 0.05) and 22% (P < 0.05) on the lower leg (spreading sensitization). Within the LE group, pressure-pain thresholds were on average reduced by 20% (P < 0.05) and pain tolerance by 10% (nonsignificant) on the painful compared with the asymptomatic side. Spatial summation (P < 0.01) and temporal summation (P < 0.05) was facilitated in LE compared with controls. In LE patients without signs of peripheral inflammation assessed by Doppler ultrasound, temporal summation was significantly stronger than in patients with ongoing inflammation (P < 0.01). CONCLUSION.: Patients with LE may be subgrouped based on pain hypersensitivity and Doppler ultrasound into clinically meaningful subgroups with varying duration of symptoms and different degrees of central sensitization. These groups may require different pain management strategies.

The effect of isometric exercise of the hand on the synovial blood flow in patients with rheumatoid arthritis measured by color Doppler ultrasound.

In 90% of patients with rheumatoid arthritis (RA), the joints of the hand are affected. Studies of grip strength training have not indicated a negative effect on disease activity after training. Introduction of ultrasound Doppler (USD) to measure increased blood flow induced by inflammation has made it possible to investigate the direct effect on blood supply in the synovium after training. In this case-control study, 24 patients with RA with USD activity in the wrist joint participated. The USD activity was measured by the color fraction (CF) (CF = colored pixels/total number of pixels in ROI). Twenty-four patients were assigned to an 8-week grip strength training program. At baseline and after 8 weeks of training, an USD examination of the wrist joint was performed. In the training group, we measured grip strength and pain in the wrist joint. Six patients withdrew from the training because of pain or change in medication. Eighteen patients served as control group. There was a modest, not significant, decrease in the CF in response to training (1.86%; P = 0.08). Grip strength increased 8.8% after training (P = 0.055). Pain in motion deceased after training (P = 0.04). No difference in the CF was seen between the training and control groups, neither at baseline nor at follow-up (P = 0.82 and P = 0.48). Patients withdrawing from training had a significantly higher CF than the other patients (P > 0.001). The results in this study might indicate that the flow in the synovium assessed by USD is not affected by grip strength training.

Changes in bone marrow lesions in response to weight-loss in obese knee osteoarthritis patients: a prospective cohort study.

BACKGROUND: Patients are susceptible for knee osteoarthritis (KOA) with increasing age and obesity and KOA is expected to become a major disabling disease in the future. An important feature of KOA on magnetic resonance imaging (MRI) is changes in the subchondral bone, bone marrow lesions (BMLs), which are related to the future degeneration of the knee joint as well as prevalent clinical symptoms. The aim of this study was to investigate the changes in BMLs after a 16-week weight-loss period in obese subjects with KOA and relate changes in BMLs to the effects of weight-loss on clinical symptoms. METHODS: This prospective cohort study included patients with a body mass index ≥ 30 kg/m2, an age ≥ 50 years and primary KOA. Patients underwent a 16 weeks supervised diet program which included formula products and dietetic counselling (ClinicalTrials.gov: NCT00655941). BMLs in tibia and femur were assessed on MRI before and after the weight-loss using the Boston-Leeds Osteoarthritis Knee Score. Response to weight-loss in BML scores was dichotomised to patients experiencing a decrease in BML scores (responders) and patients who did not (non-responders). The association of BMLs to weight-loss was assessed by logistic regressions and correlation analyses. RESULTS: 39 patients (23%) were classified as responders in the sum of all BML size scores whereas 130 patients (77%) deteriorated or remained stable and were categorized as non-responders. Logistic regression analyses revealed no association between weight-loss < or ≥ 10% and response in BMLs in the most affected compartment (OR 1.86 [CI 0.66 to 5.26, p=0.24]). There was no association between weight-loss and response in maximum BML score (OR 1.13 [CI 0.39 to 3.28, p=0.81]). The relationship between changes in BMLs and clinical symptoms revealed that an equal proportion of patients classified as BML responders and non-responders experienced an OMERACT-OARSI response (69 vs. 71%, p=0.86). CONCLUSIONS: Weight-loss did not improve the sum of tibiofemoral BML size scores or the maximum tibiofemoral BML score, suggesting that BMLs do not respond to a rapidly decreased body weight. The missing relationship between clinical symptoms and BMLs calls for further investigation.

Correlation between computer-aided dynamic gadolinium-enhanced MRI assessment of inflammation and semi-quantitative synovitis and bone marrow oedema scores of the wrist in patients with rheumatoid arthritis--a cohort study.

OBJECTIVE: To test the correlation between assessment of inflammation using dynamic contrast-enhanced MRI (DCE-MRI) analysed by a novel computer-aided approach and semi-quantitative scores of synovitis and bone marrow oedema (BME) using the OMERACT-RA MRI Scoring (RAMRIS) system, in the wrist of patients with RA. METHODS: Fifty-four RA patients had conventional and DCE-MRI of a symptomatic wrist using a low-field 0.2T extremity scanner. RAMRIS synovitis and BME of the wrist joint were done. DCE-MRI data were analysed in three ways: (i) in all images (fully automated approach), (ii) within a large extended region of interest (ROI) placed around the wrist joint (semi-automated approach) and (iii) within a small ROI placed in the area with most visual enhancement (semi-automated approach). Time spent on each procedure was noted. Spearman's rank correlation test was applied to assess the correlation between RAMRIS and the computer-generated dynamic parameters. RESULTS: RAMRIS synovitis (range 2-9), BME (range 0-39) and the dynamic parameters reflecting the number of enhancing voxels were significantly correlated, especially when an extended ROI around the wrist was used (ρ = 0.74; P < 0.01 for synovitis and ρ = 0.82; P < 0.01 for BME). The observer spent on average 20 min (range 12-25 min) to perform RAMRIS, including acquisition of the results in the database, and 8 min (range 7-10 min) to perform all above-mentioned computer-aided analyses. CONCLUSION: Computer-aided analysis of DCE-MRI data correlated with RAMRIS synovitis and BME and was twice as fast to perform. This technique may be useful for quick semi-automated assessment of joint inflammation, but needs further validation.

Feasibility of a standardized ultrasound examination in patients with rheumatoid arthritis: a quality improvement among rheumatologists cohort.

BACKGROUND: Quality improvement is important to facilitate valid patient outcomes. Standardized examination procedures may improve the validity of US.The aim of this study was to investigate the learning progress for rheumatologists during training of US examination of the hand in patients with rheumatoid arthritis (RA). METHODS: Rheumatologists with varying degrees of experience in US were instructed by skilled tutors. The program consisted of two days with hands-on training followed by personal US examinations performed in their individual clinics. Examinations were sent to the tutors for quality control. The US examinations were evaluated according to a scoring sheet containing 144 items. An acceptable examination was defined as > 80% correct scores. RESULTS: Thirteen rheumatologists participated in the study. They included a total of 104 patients with RA. Only few of the initial examinations were scored below 80%, and as experience increased, the scores improved (p = 0.0004). A few participants displayed decreasing scores.The mean time spent performing the standardized examination procedure decreased from 34 min to less than 10 minutes (p = 0.0001). CONCLUSION: With systematic hands-on training, a rheumatologist can achieve a high level of proficiency in the conduction of US examinations of the joints of the hand in patients with RA. With experience, examination time decreases, while the level of correctness is maintained. The results indicate that US may be applied as a valid measurement tool suitable for clinical practice and in both single- and multi-centre trials.

Probing cellular health at the muscle level-Multi-frequency bioimpedance in Parkinson's disease.

Bioimpedance (mfBIA) non-invasively assesses cellular muscle health. Our aim was to explore whether mfBIA captures abnormal cellular muscle health in patients with Parkinson's Disease (PD) and how such changes are modulated with the use of Parkinson's medication. In patients with PD (n = 20) mfBIA measurements were made of biceps brachii, triceps, and extensor carpi radialis longus muscles of the more affected arm whilst at rest, using a mobile mfBIA device (IMPEDIMED, Australia). mfBIA 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. Age and sex-matched healthy subjects (HC; n = 20) served as controls. PD and HC mfBIA parameters were compared by applying an unpaired two-tailed adjusted t-test and ANOVA with Tukey's correction for multiple comparisons (p ≤ 0.05). The PD group consisted of 13 men (71 ± 17 years) and 7 women (65 ± 7 years). Independent of medication, internal (Ri ) and external resistance (Re ) were found to be significantly higher, and membrane capacitance (Mc) significantly lower, in m.biceps brachii in PD subjects compared to HC. Center frequency (fc) was significantly higher in m.biceps brachii of PD subjects in the "medication-off" state. There was no difference between PD and HC in mfBIA parameters in the measured extensor muscles. The upper limb flexor muscle shows a difference in mfBIA parameters in PD compared to HC. mfBIA may be useful in the diagnosis and assessment of PD patients and is objective, non-invasive, reliable, and easy to use.

Ultrasound Doppler measurements predict success of treatment with anti-TNF-α drug in patients with rheumatoid arthritis: a prospective cohort study.

OBJECTIVE: To investigate the predictive ability of core outcomes applied in RA trials, including ultrasound (US) Doppler (USD) measurements differentiating patients who remain on anti-TNF-α therapy following 1 year. METHODS: Patients with RA in anti-TNF-α therapy were followed 1 year after therapy initiation. All patients had wrist involvement. At baseline, 2 weeks, 26 weeks and 1 year a USD examination, clinical examination including tender and swollen joint count, visual analogue scale (VAS) global and HAQ, biochemical measures and 28-joint DAS (DAS28) were collected for all patients. The amount of USD signal in the synovium was quantified by measuring the percentage of colour pixels-the colour fraction (CF). Predictive validity for patients who remain on anti-TNF-α therapy after 1 year was assessed for both USD measurements and other disease measures. Baseline values of disease measures of patients who remained on treatment after 1 year was compared with those who stopped therapy. RESULTS: The study cohort consisted of 109 patients. In this study, the baseline CF was the only measure predicting which patients would stay on the initial anti-TNF-α therapy for 1 year, evaluated using the square-root of CF (P = 0.024). The other disease markers could not significantly differentiate between the two groups of patients, with P-values of 0.86 and 0.98 for tender and swollen joint count, respectively, 0.86 for CRP, 0.24 for VAS, 0.10 for HAQ and 0.38 for DAS28. CONCLUSION: There is now evidence to support that baseline USD, in contrast to clinical measures, can predict which patients will remain on anti-TNF-α 1 year after initiating therapy.

Mortality in a cohort of Danish patients with fibromyalgia: increased frequency of suicide.

OBJECTIVE: A previous study demonstrated an association between self-reported widespread body pain and increased mortality. The aim of this study was to analyze whether fibromyalgia (FM) and FM-like symptoms are related to increased mortality. METHODS: From hospital records, we identified 1,361 patients referred during the period 1984-1999 because of the suspicion of FM. The cases were reviewed by reviewers who were blinded to the outcome. The cohort was followed up for a total of 5,295 person-years at risk and was linked to the Danish Mortality Register. Using the number of years at risk and sex-, age-, and calendar-specific mortality rates from the general population, cause-specific standardized mortality ratios [SMRs] were calculated. RESULTS: We observed no overall increased mortality among patients with FM. Among the 1,269 female patients, the SMRs (95% confidence intervals [95% CIs]) for an increased risk of death from suicide, liver cirrhosis/biliary tract disease, and cerebrovascular disease were 10.5 (95% CI 4.5-20.7), 6.4 (95% CI 2.3-13.9), and 3.1 (95% CI 1.1-6.8), respectively. The suicide risk was increased at the time of diagnosis and remained increased after 5 years. Patients meeting the American College of Rheumatology criteria for FM and patients with possible FM had the same cause-specific mortality pattern. No increased cause-specific mortality was observed in the 84 male patients. CONCLUSION: The causes of a markedly increased rate of suicide among female patients with FM are at present unknown but may be related to increased rates of lifetime depression, anxiety, and psychiatric disorders. Risk factors for suicide should be sought at the time of the diagnosis of FM and at followup. The results also suggest that risk factors for liver disease and cerebrovascular disease should be evaluated in patients with FM.

Test-retest of computerized health status questionnaires frequently used in the monitoring of knee osteoarthritis: a randomized crossover trial.

BACKGROUND: To compare data based on touch screen to data based on traditional paper versions of questionnaires frequently used to examine patient reported outcomes in knee osteoarthritis patients and to examine the impact of patient characteristics on this comparison METHODS: Participants were recruited from an ongoing trial (http://ClinicalTrials.Gov Identifier: NCT00655941). 20 female participants, mean age 67 (SD 7), completed KOOS, VAS pain, function and patient global, SF-36, Physical Activity Scale, painDETECT, and the ADL Taxonomy. Patients were randomly assigned to one of two subgroups, completing either the paper or touch screen version first. Mean, mean differences (95% CI), median, median differences and Intraclass Correlation Coefficients (ICCs) were calculated for all questionnaires. RESULTS: ICCs between data based on computerized and paper versions ranged from 0.86 to 0.99. Analysis revealed a statistically significant difference between versions of the ADL Taxonomy, but not for the remaining questionnaires. Age, computer experience or education-level had no significant impact on the results. The computerized questionnaires were reported to be easier to use. CONCLUSION: The computerized questionnaires gave comparable results to answers given on paper. Patient characteristics did not influence results and implementation was feasible.

Liraglutide after diet-induced weight loss for pain and weight control in knee osteoarthritis: a randomized controlled trial.

BACKGROUND: Weight loss is critical for preventing and managing obesity-related diseases. There is a notable lack of valid and reliable means to manage patients with overweight/obesity and knee osteoarthritis (KOA). OBJECTIVE: To determine the efficacy and safety of liraglutide in a 30 mg/d dosing in patients with overweight/obesity and KOA. METHODS: The trial was designed as a randomized controlled trial including patients between the age of 18 and 74 y with KOA and a BMI ≥27 (measured in kg/m2).Patients underwent a pre-random assignment diet intervention (week -8 to 0). At week 0, patients having lost >5% of their body weight were randomly assigned to liraglutide 3 mg/d or placebo for 52 wk. The coprimary outcomes were changes in body weight and the Knee injury and Osteoarthritis Outcome Score (KOOS) pain subscale from week 0 to 52. RESULTS: In total, 168 patients enrolled and 156 were randomly assigned to receive liraglutide or placebo. Patients experienced a significant reduction in body weight and KOOS pain during the pre-random assignment dietary intervention period (week -8 to 0). From week 0 to 52 there was a significant difference in body weight between the liraglutide and placebo group (mean changes: -2.8 and +1.2 kg, respectively; group difference, 3.9 kg; 95% CI: -6.9, -1.0; P = 0.008). There was, however, no group difference in KOOS pain (mean changes: 0.4 and -0.6 points, respectively; group difference, 0.9 points; 95% CI: -3.9, 5.7; P = 0.71). Treatment-emergent adverse events related to the gastrointestinal system were experienced by 50.2% and 39.2% of patients in the liraglutide and placebo groups, respectively. CONCLUSIONS: In patients with KOA and overweight/obesity liraglutide added after an 8-wk pre-random assignment diet induced a significant weight loss at >52 wk but did not reduce knee pain compared to placebo. This trial was registered at clinicaltrials.gov as NCT02905864.

1H NMR spectroscopy-based interventional metabolic phenotyping: a cohort study of rheumatoid arthritis patients.

1H NMR spectroscopy-based metabolic phenotyping was used to identify biomarkers in the plasma of patients with rheumatoid arthritis (RA). Forty-seven patients with RA (23 with active disease at baseline and 24 in remission) and 51 healthy subjects were evaluated during a one-year follow-up with assessments of disease activity (DAS-28) and 1H NMR spectroscopy of plasma samples. Discriminant analysis provided evidence that the metabolic profiles predicted disease severity. Cholesterol, lactate, acetylated glycoprotein, and lipid signatures were found to be candidate biomarkers for disease severity. The results also supported the link between RA and coronary artery disease. Repeated assessment using mixed linear models showed that the predictors obtained from metabolic profiles of plasma at baseline from patients with active RA were significantly different from those of patients in remission (P=0.0007). However, after 31 days of optimized therapy, the two patient groups were not significantly different (P=0.91). The metabolic profiles of both groups of RA patients were different from the healthy subjects. 1H NMR-based metabolic phenotyping of plasma samples in patients with RA is well suited for discovery of biomarkers and may be a potential approach for disease monitoring and personalized medication for RA therapy.