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.

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.

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.

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.

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.

Urinary markers of altered collagen metabolism in fibromyalgia patients.

OBJECTIVE: To assess the metabolism of collagen in fibromyalgia (FM) patients, and to compare the occurrence of collagen metabolism markers to the severity of FM symptoms. METHODS: Morning urine was collected from 27 FM women fulfilling the American College of Rheumatology (ACR) criteria for FM, and from seven controls. FM patients completed the Fibromyalgia Impact Questionnaire (FIQ). Bone mineral density (BMD), isokinetic muscle strength in knee and elbow, and hand-grip strength were measured. Urinary concentrations of collagen type I cross-linked C-telopeptide (CTX-I) and collagen type II cross-linked C-telopeptide (CTX-II) were determined by enzyme-linked immunosorbent assay (ELISA). Pyridinoline (Pyd) and deoxypyridinoline (Dpd) were determined by liquid chromatography, and hydroxyproline (Hyp) by spectrophotometry. All concentration data were normalized to creatinine. RESULTS: Mean values in the FM group and the control group, respectively, were: urinary CTX-I 246.8 and 337.5 microg/mmol (p = 0.060); CTX-II 110.4 and 185.1 ng/mmol (p = 0.035); Pyd 56.1 and 52.3 nmol/mmol (NS); Dpd 15.1 and 14.0 nmol/mmol (NS); Pyd : Dpd ratio 4.05 and 3.96 (NS); Hyp 26.1 and 21.1 micromol/mmol (NS). Significant inverse correlations were seen between CTX-I and the intensity of fatigue, and between CTX-II and anxiety. An inverse correlation between CTX-I and muscle strength was apparent, but relied on extreme values from one patient, and no significant correlation was found between CTX-I or CTX-II and tender points or BMD in the FM group. CONCLUSIONS: Low urinary concentrations of CTX-II and CTX-I and normal levels of Pyd and Dpd were found in FM, but their relationship to the intensity of FM symptoms was unclear.

A randomized, controlled study of a single intra-articular injection of etanercept or glucocorticosteroids in patients with rheumatoid arthritis.

OBJECTIVE: Glucocorticosteroids are used successfully for both systemic and intra-articular treatment of arthritis. Inhibitors of tumour necrosis factor alpha (TNF-alpha) are effective when administered systemically and this study was performed to compare the effect of intra-articular injection of these two substances. DESIGN: A randomized, parallel-group, double-blind study with an independent observer. Thirty-eight patients with flare of arthritis in a single joint (wrist, elbow, or knee) were given intra-articular 25 mg etanercept or 40 mg methylprednisolone guided by ultrasound. The primary end-point was the 4-week change in pain in the target joint. The study complied with Good Clinical Practice (GCP) and the Consolidated Standards for Reporting of Trials (CONSORT) statement. RESULTS: At 4 weeks no difference in pain outcome between treatment groups was demonstrated by analysis of covariance (ANCOVA). Pain on the Visual Analogue Scale (VAS) for etanercept was baseline mean 40.9 (SD 19.6) mm, follow-up 32.7 (29.1) mm (p = 0.29), methylprednisolone baseline mean 47.1 (29.6) mm, follow-up 25.3 (24.7) mm (p<0.001). The investigator's evaluation was for etanercept baseline 30.6 (21.2) mm, follow-up 17.1 (15.5) mm (p = 0.054) and for methylprednisolone baseline 35.4 (26.4) mm, follow-up 11.9 (14.6) mm (p = 0.012). Joint swelling was for etanercept baseline 1.78 (0.73), follow-up 1.25 (0.77) (p = 0.015) and for methylprednisolone baseline 1.74 (0.73), follow-up 0.71 (0.77) (p<0.001). One serious adverse event was seen in a patient treated with methylprednisolone injection. CONCLUSION: Although no difference between groups was demonstrated, the within-group effect of methylprednisolone was more marked than that of etanercept. Injections with 25 mg etanercept were well tolerated. However, the cost of etanercept will presumably limit its use to patients with adverse reactions to steroid.

Collagen structure in skin from fibromyalgia patients.

The distribution and amount of collagen in skin from a non-tender-point area from fibromyalgia patients was assessed by quantitative analysis of amino acids and by electron and light microscopy. Skin biopsies were obtained from the front of the thigh of 27 females who fulfilled the American College of Rheumatology criteria of fibromyalgia and from eight control subjects who were matched for gender, age and physical activity. Amino acids were determined by high-performance liquid chromatography. Electron and light microscopic investigations were carried out to examine tissue structure. Among the collagen-related amino acids, the mean number of hydroxyproline residues per 1,000 residues was 52.5 and 63.4 in fibromyalgia patients and control subjects, respectively (p = 0.050); proline residues were 81.7 and 110.0 (p = 0.006); and hydroxylysine residues were 14.7 and 10.1 (p = 0.002). The total amount of skin protein in proportion to dry tissue weight was 83.4% and 72.6% in fibromyalgia and controls, respectively (p = 0.037). The overall microscopic picture was normal. The lamellar structure of the perineurium and a deficiency in collagen packing in the endoneurium was observed more frequently and to a larger extent in fibromyalgia patients than in controls. In conclusion, there are some differences between the amino acid composition of skin proteins in fibromyalgia patients compared with controls. The amount of collagen may be lower in skin from fibromyalgia patients, and collagen packing in the endoneurium may be less dense.

Antipolymer antibodies in Danish fibromyalgia patients.

OBJECTIVE: To use a new immunologic assay to investigate antipolymer antibody (APA) levels in women with fibromyalgia (FM). METHODS: The study population consisted of 35 patients with FM and 129 controls. The controls were selected based on a prior history of breast surgery and the presence or absence of a prior hospital diagnosis of soft tissue rheumatism. Study subjects underwent blood sampling, including tests for antinuclear antibodies (ANA) and APA, a clinical examination, and an interview focusing on rheumatic complaints and self-reported disability. The severity of rheumatic symptoms/signs was scored from 1 (= none) to 5 (= severe) based on the clinical examination and the interview. RESULTS: FM patients in this study represented a broad spectrum of disease severity, with the majority having mild symptoms. FM patients had a higher symptom severity and myalgic scores than controls (p < 0.001 for both variables). Adjusting for symptom severity, a weak positive association between APA levels and FM was observed (p = 0.08). The APA level was inversely associated with age, i.e., decreasing APA levels were seen with increasing age (p = 0.008). CONCLUSION: FM patients tended to have slightly higher APA levels than controls when adjusted for symptom severity. APA levels declined with age, a finding that has not been reported previously. The APA test and its clinical relevance should be evaluated in future studies.

Plasma TNF binding capacity profiles during treatment with etanercept in rheumatoid arthritis.

BACKGROUND: Etanercept (Enbrel) induces a rapid and sustained decline in disease activity in the majority of patients with refractory rheumatoid arthritis (RA). In these patients neutralization of TNFalpha and lymphotoxin (LT), previously termed TNFbeta is mediated by etanercept itself, as well as by naturally occurring soluble TNF receptors. However, the clinical response to treatment with etanercept may vary. Previously, pharmacokinetic studies have focused on the molar concentrations of etanercept, but very little is known about the kinetics of bioactive etanercept in patients treated with etanercept. The purpose of this study was to evaluate kinetics, including inter- and intraindividual variations of the total TNF binding capacity, in RA patients who were on a standard treatment schedule with etanercept. METHODS: Plasma samples were collected daily from 16 RA patients who were in the steady-state phase during treatment with etanercept 25 mg subcutaneous once (n = 2) or twice (n = 14) weekly. The inflammatory activity, including Health Assessment Questionnaire (HAQ) score, numbers of painful and swollen joints, and ESR, was assessed at inclusion; CRP was measured on a daily basis. The samples were incubated with human recombinant LT to a concentration of 1000 pg/mL and the levels of detectable LT were measured by ELISA specific for free LT. The LT binding capacity (LTBC) was expressed in arbitrary units (AU) as the percentage value of bound LT to added LT. RESULTS: The median LTBC values measured during the treatment schedule from Day 1 (before the injection) to Day 4 (before the next injection) were 47 AU. The LTBC values in each individual patient generally remained fairly stable through the treatment schedule, and there were no significant differences in LTBC levels in samples obtained on a daily basis during the treatment schedule. However, a pronounced variation between the patients was noticed with LTBC values ranging from 10-82 AU (coefficient of variation=38%). No significant association was found between LTBC levels and clinical measures of disease activity, including HAQ and numbers of swollen or painful joints. However, among patients with high LTBC levels (> or =65 AU), elevated levels of ESR and CRP were less frequent (0%) compared with patients who had lower LTBC levels, in which the frequencies of elevated ESR and CRP were 53% and 37%, respectively. Soluble TNF receptor 1 (sTNFR1) remained stable between the injections and correlated with the number of swollen joints, but did not correlate with LTBC values. CONCLUSION: LTBC levels appeared stable in each individual RA patient who was on the standard treatment schedule with weekly injections of etanercept, but the inter-individual variations were considerable.

Collagen and muscle pathology in fibromyalgia patients.

OBJECTIVE: To measure collagen concentration and search for muscle pathology in muscle non-tender-point areas from fibromyalgia (FM) patients. METHODS: Muscle biopsies were obtained from m. vastus lateralis of 27 carefully selected, female fibromyalgia patients, and from eight age-matched female control subjects. Amino acids were determined by HPLC and electron microscopy was performed. RESULTS: The FM patients had lower hydroxyproline and lower total concentration of the major amino acids of collagen than the controls. No significant difference was seen in the concentration of the major amino acids of myosin or of total protein. Electron microscopy showed no significant differences between FM patients and controls although atrophied muscle fibrils occurred in FM patients only, but frequencies were not significantly different. CONCLUSION: Fibromyalgia patients had a significantly lower amount of intramuscular collagen. This may lower the threshold for muscle micro-injury and thereby result in non-specific signs of muscle pathology.

Bone mineral density in fibromyalgia patients--correlation to disease activity.

OBJECTIVE: To compare bone mass (BMD) in women with fibromyalgia (FM) with healthy females, and to evaluate whether self-reported pain and lack of functional capacity correlate to reduced BMD in FM patients. METHODS: Thirty-one FM patients (20 pre- and 11 postmenopausal) and fourty-one healthy women (30 pre- and 10 postmenopausal) were enrolled in the study. BMD of the lumbar spine and the femoral neck was measured by a DEXA (Norland) scanner. Self reported pain was measured on a Visual Analog Scale (VAS). The Activity of Daily Living (ADL) component of the Fibromyalgia Impact Questionnaire (FIQ-ADL) was used as measure for physical capacity. RESULTS: BMD-lumbar spine and BMD-femoral neck did not differ significantly between FM patients and controls, though premenopausal FM patients tended to have lower BMD-femoral neck (p = 0.09). Self reported pain and FIQ-ADL among FM patients correlated with BMD-femoral neck (r(s) = -0.52, p = 0.003); (r(s) = -0.31, p = 0.09). CONCLUSION: Premenopausal FM patients tended to have lower BMD of hip than controls. Self reported pain correlated negatively to BMD. Thus, the severity of FM might have a negative impact on bone mass.

Postural sway in normal subjects aged 20-70 years.

So far, no population-based reference material of postural sway has been presented in the literature. This study evaluated postural control by measuring posturographic parameters, with the aim of establishing useful standards with regard to gender, age, body weight, cigarette smoking, alcohol consumption and articular hypermobility. This was performed in an age-stratified random sample of 195 subjects from the Copenhagen City Heart Study, of whom, 133 agreed to participate. Measurement of postural sway was performed the Balance Master Pro(R). Outcome parameters were average angular velocity, target sway area, per cent maximum stability and per cent ankle strategy. Using SAS Proc Mixed, backward stepwise elimination was performed and 95% prediction intervals were obtained. Sway increased with increasing difficulty of the test (P<0.001) and with increasing age (P<0.001). No differences were found between the sexes. Ankle-strategy did not change with age, but decreased with increasing body weight, and increased in subjects reporting a consumption of modest amounts of alcohol (P<0.001), or with the finding of increased hypermobility (P = 0.006). The present material may be used as a reference in further studies of postural control.

Silicate antibodies in Danish women with silicone breast implants.

OBJECTIVES: To use a new immunological assay to evaluate silicate antibody levels in women with and without silicone breast implants (SBIs). METHODS: Women (n=186) were identified through Danish population-based registers and categorized into six groups defined by prior breast surgery (breast implantation/breast reduction/no breast surgery) and by the presence or absence of prior hospital diagnoses of soft-tissue rheumatism (muscular rheumatism, ICD-8 codes 717.90 and 717.99). The women underwent blood tests, a silicate antibody assay and a clinical examination. Severity of rheumatic symptoms/signs was scored from 1 (none) to 5 (severe). RESULTS: The level of silicate antibodies was not significantly different between the three groups with prior soft-tissue rheumatism (P > 0.5), with the lowest value among women with SBIs. Among women who had no prior diagnosis of soft-tissue rheumatism, silicate antibody levels were highest in women with SBIs (P < 0.01). No significant correlations were observed between silicate antibody levels and symptom severity scores. CONCLUSIONS: Silicate antibodies were not consistently associated with SBIs and were not correlated with rheumatic symptoms. The clinical relevance of these antibodies remains questionable.

Effects of treatment with etanercept (Enbrel, TNRF:Fc) on rheumatoid arthritis evaluated by Doppler ultrasonography.

OBJECTIVE: to estimate and visualise the efficacy of treatment with etanercept (Enbrel) in patients with rheumatoid arthritis (RA) using colour Doppler and spectral Doppler ultrasonography to determine the possible changes in synovial perfusion during a one year observation period. METHODS: Eleven patients from the European multicentre trial of the efficacy and safety of etanercept were included in this study when transferred into the open label, long term safety, and efficacy study. Before a scheduled dosage increase to 50 mg/week they were examined clinically, serologically, and by ultrasonography using the colour Doppler pixels and the spectral Doppler resistance index (RI) as indicators of inflammation. The patients were re-examined at two weeks and at one year follow up RESULTS: The clinical activity decreased significantly from baseline to week 2, but no significant changes were seen from baseline to one year. The number of coloured pixels in each region of interest decreased from baseline to week 2 with a median reduction of 60% (p=0.005). This effect on the perfusion in the synovium could not be found after one year of treatment. During the initial treatment we detected an increase in synovial RI by spectral Doppler. The median increase in peripheral resistance from baseline to week 2 as estimated by the mean RI was 22.6% (p=0.005). The increase in peripheral resistance was maintained to some extent after one year (mean RI increased by 18.8% p=0.074). CONCLUSION: Ultrasonography seems to be a promising tool for the detection of treatment response using spectral Doppler and pixel estimation.

Self-reported symptoms among Danish women following cosmetic breast implant surgery.

The aim of this study was to examine self-reported symptomatology and to identify distinctive characteristics among women with silicone breast implants (SBI). Using the Danish hospital and population registers we identified three groups of women with a hospital diagnosis of muscular rheumatism (a nonspecific soft-tissue diagnostic code) who had previously undergone SBI surgery (n = 28), breast reduction surgery (n = 29) or no breast surgery (n = 27); and three groups of women without a diagnosis of muscular rheumatism who had undergone SBI surgery (n = 21), breast reduction surgery (n = 27) or no breast surgery (n = 56). All study subjects completed a self-administered questionnaire focusing on sociodemographic factors, lifestyle habits, somatic symptoms and psychological symptoms. Women with SBI and women with breast reduction with no previous diagnosis of muscular rheumatism had similar patterns of reporting for most symptoms and characteristics. They reported significantly more somatic symptoms and psychological distress, including somatisation, obsessive-compulsiveness and depression, than women with no breast surgery. No significant differences in self-reported symptomatology and characteristics were observed among the three groups of women with a previous diagnosis of muscular rheumatism. Overall, women with prior muscular rheumatism reported more symptoms than those without. We concluded that self-reported somatic symptoms among women with SBI were similar to those of controls. Women with cosmetic breast surgery appear to have distinctive psychological characteristics. Our study emphasises the importance of taking the psychological profile and previous history of rheumatic diseases into account when examining women with SBI.

[Biochemical changes in fibromyalgia. Can serum hyaluronic acid be used diagnostically?]. / Biokemiske forandringer ved fibromyalgi. Kan serum-hyaluronsyre bruges diagnostisk?

AIM: To assess the levels of hyaluronic acid (HA) in Danish patients with fibromyalgia (FM). METHODS: Serum levels of HA were determined in 53 patients with established FM and 55 control samples with a radiometric assay (Pharmacia). Values were correlated to clinical parameters of disease severity (duration of disease, tender point scales, visual analogue scales). RESULTS: There were no differences in the HA levels of patients and controls. In all the patients, except one, values were within the reference intervals. Nor was there an association between HA levels and clinical findings. CONCLUSIONS: Patients with FM do not generally have increased serum levels of HA, and other serum measurements have not been helpful in the diagnosis of FM. Some biochemical changes have been described in FM, however, and these have mainly been observed in the spinal fluid.