Cognitive behavioural therapy for insomnia in patients with rheumatoid arthritis: protocol for the randomised, single-blinded, parallel-group Sleep-RA trial.

BACKGROUND: More than half of patients with rheumatoid arthritis complain of insomnia, which is predominantly treated with hypnotic drugs. However, cognitive behavioural therapy for insomnia is recommended as the first-line treatment in international guidelines on sleep. Patients with rheumatoid arthritis suffer from debilitating symptoms, such as fatigue and pain, which can also be linked to sleep disturbance. It remains to be determined whether cognitive behavioural therapy for insomnia can be effective in patients with rheumatoid arthritis. The aim of the Sleep-RA trial is to investigate the efficacy of cognitive behavioural therapy for insomnia on sleep and disease-related symptoms in patients with rheumatoid arthritis. The primary objective is to compare the effect of cognitive behavioural therapy for insomnia relative to usual care on changes in sleep efficiency from baseline to week 7 in patients with rheumatoid arthritis. The key secondary objectives are to compare the effect of cognitive behavioural therapy for insomnia relative to usual care on changes in sleep onset latency, wake after sleep onset, total sleep time, insomnia, sleep quality, fatigue, impact of rheumatoid arthritis and depressive symptoms from baseline to week 26 in patients with rheumatoid arthritis. METHODS: The Sleep-RA trial is a randomised controlled trial with a two-group parallel design. Sixty patients with rheumatoid arthritis, insomnia and low-to-moderate disease activity will be allocated 1:1 to treatment with cognitive behavioural therapy for insomnia or usual care. Patients in the intervention group will receive nurse-led, group-based cognitive behavioural therapy for insomnia once a week for 6 weeks. Outcome assessments will be carried out at baseline, after treatment (week 7) and at follow-up (week 26). DISCUSSION: Data on treatment of insomnia in patients with rheumatoid arthritis are sparse. The Sleep-RA trial is the first randomised controlled trial to investigate the efficacy of cognitive behavioural therapy for insomnia in patients with rheumatoid arthritis. Because symptoms of rheumatoid arthritis and insomnia have many similarities, we also find it relevant to investigate the secondary effects of cognitive behavioural therapy for insomnia on fatigue, impact of rheumatoid arthritis, depressive symptoms, pain, functional status, health-related quality of life and disease activity. If we find cognitive behavioural therapy for insomnia to be effective in patients with rheumatoid arthritis this will add weight to the argument that evidence-based non-pharmacological treatment for insomnia in rheumatological outpatient clinics is eligible in accordance with the existing international guidelines on sleep. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03766100. Registered on 30 November 2018.

Inter-examiner reproducibility of tests and criteria for generalized joint hypermobility and benign joint hypermobility syndrome.

OBJECTIVE: To test the reproducibility of tests and criteria for generalized joint hypermobility (GJH) and benign joint hypermobility syndrome (BJHS). METHODS: A standardized protocol for clinical reproducibility studies was followed using a three-phase study (with a training, an overall agreement and a test phase). An overall agreement of at least 0.80 was required to proceed to the test phase. Phases 1, 2 and 3 used 14 patients (with varying degrees of hypermobility), 20 patients (50% cases) and 40 patients (50% cases), respectively. The inclusion criterion for cases was hypermobility (patients with Ehlers-Danlos Syndrome or BJHS) and for controls, non-hypermobility (patients with shoulder and/or back pain); patients were selected from patients' files (phases 1 and 2) or included consecutively from our outpatient clinic (phase 3). RESULTS: The overall agreement in phase 2 was 0.95 for GJH and 0.90 for BJHS. Reproducibility for diagnosing GJH and BJHS in phase 3 showed kappa values of 0.74 and 0.84, respectively. Kappa in the Beighton tests for diagnosing GJH (currently or historically) was generally above 0.80, except for the fifth fingers and elbows (> or = 0.60). In the Brighton tests for diagnosing BJHS, kappa was above 0.73, except for the skin signs (0.63). Lowest kappa was found in the Rotès-Quérol tests, where it was > or = 0.57, except for the right shoulder (0.31). CONCLUSION: We found a good-to-excellent reproducibility of tests and criteria for GJH and BJHS. Future research on the validity of the tests and criteria for joint hypermobility is urgently needed.

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.

Effect of static stretching of quadriceps and hamstring muscles on knee joint position sense.

OBJECTIVES: To evaluate if a stretch regimen consisting of three 30 second stretches would alter joint position sense (JPS). METHODS: A blinded, randomised, cross over design with a washout time of 24 hours was used with 20 healthy volunteers. JPS was estimated from the ability to reproduce the same position in one knee (target versus estimated angle) expressed as the difference between target and estimated angle (constant error, CE). Measurements were repeated three times in a sitting and a prone position on the dominant leg measured before and immediately after the static stretch. The static stretch consisted of a 30 second stretch followed by a 30 second pause, repeated three times. RESULTS: At baseline, the mean (SD) CE was -2.71 (3.57) degrees in the sitting position. No difference (p = 0.99) in CE between stretching and control was observed (0.00; 95% confidence interval -0.98 to 0.99). At baseline, the CE was -3.28 (4.81) degrees in the prone position. No difference (p = 0.89) in CE between stretching and control was observed (0.12; 95% confidence interval -1.52 to 1.76). CONCLUSION: A static stretch regimen had no effect on JPS in healthy volunteers.

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.

Comparison of Kistler 9861A force platform and Chattecx Balance System for measurement of postural sway: correlation and test-retest reliability.

Measurement of postural sway has several potential applications in sports medicine. Traditionally, however, rather complicated equipment has been applied. The purpose of the study was to compare two devices based on two different methods of measuring postural sway: (i) a sophisticated Kistler 9861A force platform (KIS)--which all but requires a laboratory setting--and (ii) Chattecx Balance System (CBS)--which is particularly suited for measurement of sway in the dynamic environment of sports. Measurement of sway was performed in 29 subjects twice at baseline and twice at follow-up 2-4 weeks later. One measurement consisted of four 25-second sequences (eyes open, parallel feet; eyes closed, parallel feet; eyes open, tandem Romberg; eyes closed, tandem Romberg). Factor analysis revealed influence of sight and stance on sway, marked interaction between these two factors and a decrease in sway on retest on the same day. Coefficients of variation were--KIS: 0.13-0.23; CBS: 0.11-0.25. Body height was a covariate for all parameters. Kistler 9861A force platform and CBS were correlated (baseline: r(s) = 0.47; follow-up: r(s) = 0.9). These findings suggest that, when the effects of acclimatization and covariance of body height were taken into account, CBS was as reliable and reproducible as KIS in our laboratory.

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.

Rheumatic manifestations in danish women with silicone breast implants.

The aim of this study was to investigate whether women with silicone breast implants (SBI) present with a unique rheumatic symptomatology. We assessed the profile of rheumatic disease in six groups of women identified through Danish hospital and population registers, three groups of women with a prior hospital diagnosis of muscular rheumatism (a non-specific 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 sugery (n = 56). All women in the study population (n = 188) underwent a thorough clinical examination, blood tests and a personal interview. In all study groups soft-tissue rheumatism and degenerative diseases were the most frequent diagnoses. Women with a prior diagnosis of muscular rheumatism but no prior breast surgery had a significantly higher prevalence of soft-tissue rheumatism than those with breast implant or reduction surgery. No significant differences in the frequencies of rheumatic diseases were observed among the three groups of women without previous muscular rheumatism. No specific pattern of inflammatory rheumatic disorders or soft-tissue complaints was identified among the women with SBI, and blood tests for autoimmunity revealed no unique pattern. Overall, women with earlier rheumatism had significantly increased frequencies of rheumatic conditions than did those without. We found no evidence of a rheumatic symptomatology unique to women with silicone breast implants. Our study emphasises the need for consideration of prior rheumatic disease when evaluating rheumatic manifestations in women with SBI.

[A controlled trial of training in knee arthritis]. / En kontrolleret undersøgelse af traening af knaeartrose.

INTRODUCTION: The aim was to investigate the effectiveness and safety of a physical training programme in patients with severe osteoarthritis of the knees. MATERIAL AND METHODS: Twenty-five patients participated in this randomised clinical trial with a blind observer. Intervention consisted in training twice a week for three months and focused on general fitness, balance, co-ordination, and muscle strength. Follow-up was performed at 3 and 12 months. The recorded parameters were muscle strength, algofunctional index, pain, walking speed, and clinical findings. RESULTS: At three months follow-up, muscle strength had improved in the intervention group. By one year, pain at night had decreased, but the number of palpable knee joint effusions had increased. CONCLUSION: A general physical training programme appears to be beneficial to patients with osteoarthritis of the knees, but further investigation of the safety of such a programme is called for.

Quantitative ultrasonography in rheumatoid arthritis: evaluation of inflammation by Doppler technique.

OBJECTIVE: To evaluate ultrasonographic methods, including the Doppler technique, as measures of synovial inflammation in finger joints of patients with rheumatoid arthritis. METHODS: Ultrasonography was performed with a high frequency transducer (13 MHz). Evaluation of the sonographic data was conducted by two independent observers and included measurement of synovial area and thickness (grey tone ultrasound), vascularisation (power/colour Doppler), and indices of the intra- and extrasynovial arterial flow (spectral Doppler). The flow pattern was estimated by the indices of pulsatility (PI) and resistance (RI). RESULTS: The sonographic measurements of joint space were reproducible with intraobserver, intraclass correlation coefficients (ICC) 0.82-0.97 (p<0.0001) and interobserver ICC 0.81 (p<0.0001). The mean (SD) fraction of the synovium vascularised in the patients was 0.15 (0.15). The synovial blood flow was characterised by a diastolic flow-that is, the flow persisting during the diastole. The mean (SD) PI was 1.92 (1.18) and RI 0.70 (0.13). The estimated vascular fraction correlated with the erythrocyte sedimentation rate (ESR) (r(s)=0.53, p=0.03). The relative Pi (rPi), an estimate of an abnormally low resistance to vascularisation, correlated with both ESR (r(s)=-0.557, p<0.05) and Health Assessment Questionnaire score (r(s)=-0.584, p<0.05). After an injection of contrast Levovist the vascular fraction increased, while no difference in PI and RI was observed. CONCLUSION: Ultrasonography is a reliable tool for estimating the size of the joint space and the synovial activity measured by the degree of vascularisation and pattern of flow. Ultrasonography may be useful in monitoring the synovial inflammation in rheumatoid arthritis.

MRI of the plantar structures of the foot after falanga torture.

Falanga is an ancient form of punishment or torture but is still commonly reported by our refugees. The late result of caning the heel and ball of the foot is a chronic painful condition with few clinical signs. The aim of the present study was to assess, by MRI, possible morphologic characteristics of the heel and ball of the foot, related to falanga and pain in correlation to clinical findings. Magnetic resonance imaging of the foot was obtained in 12 victims exposed to falanga torture and 9 healthy volunteers. Sagittal T1-weighted spin-echo images (TR 616-840 ms, TE 20 ms), T2-weighted spin-echo images (TR 1900 ms, TE 90 ms), and short tau inversion recovery (STIR) images (TR 1200 ms, TE 15 ms, TI 100 ms) were performed. The central portion of the plantar aponeurosis was generally significantly thicker in victims exposed to falanga torture as compared with that of controls (P < 0.05). In all except one of the victims, MRI demonstrated two layers of the thickened plantar aponeurosis: a deeper portion with normal homogeneous low signal intensity (SI) appearance, and a superficial layer with characteristic areas of mixed SI on both T1- and T2-weighted images. There were no signs of chronic muscular compartment syndromes, and the thickness of the plantar pad did not differ between the two groups. Magnetic resonance imaging may demonstrate morphologic characteristics of the plantar aponeurosis which may confirm falanga torture. Further imaging with more specific sequences is warranted to demonstrate the supposed injuries in the compartmental fat tissue chambers and the vascularity of the ball pad of the foot.

The effects of a physical training program on patients with osteoarthritis of the knees.

OBJECTIVE: To investigate physical function in patients with severe osteoarthritis (OA) of the knees during and after a general physical training program. DESIGN: Randomized control trial, blinded observer, follow-up at 3 months and 1 year. SETTING: Outpatient clinic. PATIENTS: Consecutive sample of 25 patients (3 men, 22 women) with OA of the knees according to the criteria of the American College of Rheumatology (ACR). Two patients (8%) failed to complete the study. There were no withdrawals for adverse effects. INTERVENTION: Twelve patients received training in groups of 6, twice a week for 3 months. Training focused on general fitness, balance, coordination, stretching, and lower extremity muscle strength, and included a daily home exercise program. MAIN OUTCOME MEASURES: Muscle strength across the knee (extension and flexion), Algofunctional Index (AFI), pain (0 to 10 point scale), walking speed, clinical findings. RESULTS: Patients participated in 96 of 96 assessments (100%) and in 218 of 280 training sessions (77.9%). From baseline to 3 months, isokinetic quadriceps strength (30 degrees/sec) improved 20% (confidence interval [CI] 2alpha = .05, 8% to 50%) in the least affected leg; isometric strength improved 21%. By 1 year, AFI had decreased 3.8 points (CI2alpha = .05, 1.0 to 7.0), pain had decreased 2.0 points (CI2alpha = 05, 0.0 to 4.0), and walking speed had increased 13% (CI2alpha = .05, 4% to 23%). There was an increase in the frequency of palpable joint effusions (p < .01) on the most affected side. Frequency of crepitus decreased on the least affected side (p < .01). CONCLUSIONS: General physical training appears to be beneficial to patients with OA of the knee. As shown by the high compliance and low dropout frequency, such a program is feasible even in patients with severe OA of the knee.

: a prospective, randomised, double-blind, controlled multicentre study.

The efficacy and safety of etodolac and piroxicam were compared in patients with osteoarthritis of the hip (n = 111) or knee (n = 160). Special emphasis was placed on clinical gastrointestinal adverse effects. 271 patients participated in this 8-week prospective, multicentre, randomised, double-blind trial. Efficacy was measured by patient's and investigator's assessment of key parameters after 4 and 8 weeks of treatment compared with baseline. Tolerability was evaluated by patients' complaints at each visit (adverse events) and laboratory tests performed before and at the end of treatment. After 4 and 8 weeks of treatment and at the end of treatment, patients' and investigators' assessments were significantly improved from baseline in both groups. There were no statistically significant differences between the groups in any efficacy assessment at any observation. In the etodolac group 30% reported adverse events, compared with 46% in the piroxicam group (p < 0.01). In the study, 20% in the etodolac group and 29% in the piroxicam group reported gastrointestinal adverse events (not significant). Clinically significant falls in haemoglobin occurred in 22% of patients with no significant difference between the 2 groups. In conclusion, the study indicated that etodolac 600mg per day was as effective as piroxicam 20mg per day in the treatment of osteoarthritis. Etodolac produced adverse events in a significantly smaller number of patients than piroxicam. No significant differences were found between etodolac and piroxicam with respect to incidence of clinical gastrointestinal adverse events.