Exploring the effect on primary endpoints in trials testing targeted therapy interventions for rheumatoid arthritis: a meta-epidemiological study on the appropriate use of a core outcome set.

OBJECTIVES: To explore which core domain is best associated with the American College of Rheumatology (ACR) 20% response in trials assessing the effect of targeted interventions in rheumatoid arthritis (RA). METHODS: A meta-epidemiological study was performed on randomised trials investigating biologics and targeted agents compared with placebo or conventional disease-modifying antirheumatic drugs in patients with RA. The main outcome measures were ORs for the ACR 20% response and at least one of the eight core domains according to the existing RA core outcome set (COS) analysed based on standardised mean differences. RESULTS: 115 trials involving 55 422 patients with RA were eligible. The OR for achieving ACR 20% response was 3.19 (95% CI 2.96 to 3.44) for the experimental interventions relative to the comparators. The median number of COS domains reported was 6; 18 trials reported only 1 domain, 17 all 8. Univariable meta-regression analyses indicated that each of the eight core domains was significantly associated with ACR 20% response, yet improvements in physical disability explain a successful ACR 20% response the most. Including only trials reporting on all eight core domains, univariable meta-regression analyses proved improvement in fatigue to explain a successful ACR 20% response the most. CONCLUSIONS: Within this dataset, it is evident that the conclusions concerning our primary objective were significantly influenced by both the amount and characteristics of missing data. Our data suggest that fatigue could be more important for the primary endpoint than previously assumed, but this is based on limited data.

Differentiating Lyme arthritis: a case-based review.

The incidence or prevalence of Lyme arthritis (LA) in Denmark is unknown and assumed very low. No published cases of polymerase chain reaction (PCR)-confirmed LA from Denmark exist. Clinically, LA does not differ from other rheumatic oligoarthritic disorders posing a differential diagnostic challenge. To review the incidence and prevalence of LA to our knowledge and to present a case series of PCR-confirmed LA cases from Denmark. We conducted a systematic literature review via MEDLINE and EMBASE to explore incidence and prevalence rates of LA. Additionally, we present six cases of patients diagnosed with LA in Denmark. Our literature review identified 23 studies reporting prevalence or incidence, yet only ten studies provided estimates ranging from 1.1 to 280/100.000 in the general population. Our case series identified six patients with LA from a localized region in Southern Denmark; all confirmed by Borrelia-specific real-time PCR from synovial fluid. The diagnostic delay was up to 38 months. All patients except one had a history of previous tick bites; none had erythema migrans lesions. All presented with recurrent arthritis in the knee joint, and two had arthritis in the wrist. The literature review showed an incidence of LA ranging from 1.1 to 15.8 per 100.000 in Europe. Our case series suggests a potentially higher prevalence of LA in Denmark than previously believed. Lack of tick exposure history, antibody assessments and test of Borrelia burgdorferi sensu lato DNA in synovial fluid might lead to misdiagnosed cases potentially explaining the assumed low incidence of LA in Denmark.

Comparison between conventional MRI and weight-bearing positional MRI reveals important differences in radiological measurements of the patellofemoral joint.

OBJECTIVE: To compare radiological measurements of the patellofemoral joint (PFJ) morphology and measurement reproducibility across the following scanning modalities: (a) 3 T supine MRI, (b) 0.25 T supine MRI and (c) standing 0.25 T MRI. METHODS: Forty patients referred to MRI of the knee were scanned by high field 3 T MRI in supine position and low field 0.25 T positional (pMRI) in supine and standing positions. Radiological measurements for assessment of femoral trochlear morphology, patellar tracking, patellar height and knee flexion angle were compared across scanning situations by one-way repeated-measures ANOVA. Measurement reliability and agreement were assessed by calculation of ICC, SEM and MDC. RESULTS: Patellar tracking differed across scanning situations, particularly between 3.0 T supine and 0.25 T standing position. Mean differences are the following: patella bisect offset (PBO): 9.6%, p ≤ 0.001; patellar tilt angle (PTA): 3.1°, p ≤ 0.001; tibial tuberosity-trochlear groove distance (TT-TG): 2.7 mm, p ≤ 0.001). Measurements revealed slight knee joint flexion in supine and slight hyperextension in the standing position (MD: 9.3°, P ≤ 0.001), likely related to the observed differences in patellar tracking. Reproducibility was comparable across MRI field strengths. In general, PBO, PTA and TT-TG were the most robust measurements in terms of reproducibility and agreement across scanning situations (ICC range: 0.85-0.94). CONCLUSION: Significant differences in important patellofemoral morphology measurements were observed between supine and standing MRI scanning positions. These were unlikely due to physiological factors such as changes in joint loading but rather induced by slight differences in knee flexion angle. This emphasises the need to standardise knee positioning during scanning, particularly for weight-bearing positional MRI before clinical use.

Reliability and correlation of weight-bearing cone beam CT and Foot Posture Index (FPI) for measurements of foot posture: a test-retest study.

OBJECTIVE: To assess test-retest reliability and correlation of weight-bearing (WB) and non-weight-bearing (NWB) cone beam CT (CBCT) foot measurements and Foot Posture Index (FPI) MATERIALS AND METHODS: Twenty healthy participants (age 43.11±11.36, 15 males, 5 females) were CBCT-scanned in February 2019 on two separate days on one foot in both WB and NWB positions. Three radiology observers measured the navicular bone position. Plantar (ΔNAVplantar) and medial navicular displacements (ΔNAVmedial) were calculated as a measure of foot posture changes under loading. FPI was assessed by two rheumatologists on the same two days. FPI is a clinical measurement of foot posture with 3 rearfoot and 3 midfoot/forefoot scores. Test-retest reproducibility was determined for all measurements. CBCT was correlated to FPI total and subscores. RESULTS: Intra- and interobserver reliabilities for navicular position and FPI were excellent (intraclass correlation coefficient (ICC) .875-.997). In particular, intraobserver (ICC .0.967-1.000) and interobserver reliabilities (ICC .946-.997) were found for CBCT navicular height and medial position. Interobserver reliability of ΔNAVplantar was excellent (ICC .926 (.812; .971); MDC 2.22), whereas the ΔNAVmedial was fair-good (ICC .452 (.385; .783); MDC 2.42 mm). Using all observers' measurements, we could calculate mean ΔNAVplantar (4.25±2.08 mm) and ΔNAVmedial (1.55±0.83 mm). We demonstrated a small day-day difference in ΔNAVplantar (0.64 ±1.13mm; p<.05), but not for ΔNAVmedial (0.04 ±1.13mm; p=n.s.). Correlation of WBCT (WB navicular height - ΔNAVmedial) with total clinical FPI scores and FPI subscores, respectively, showed high correlation (ρ: -.706; ρ: -.721). CONCLUSION: CBCT and FPI are reliable measurements of foot posture, with a high correlation between the two measurements.

Weight-bearing cone-beam CT: the need for standardised acquisition protocols and measurements to fulfill high expectations-a review of the literature.

Weight bearing CT (WBCT) of the lower extremity is gaining momentum in evaluation of the foot/ankle and knee. A growing number of international studies use WBCT, which is promising for improving our understanding of anatomy and biomechanics during natural loading of the lower extremity. However, we believe there is risk of excessive enthusiasm for WBCT leading to premature application of the technique, before sufficiently robust protocols are in place e.g. standardised limb positioning and imaging planes, choice of anatomical landmarks and image slices used for individual measurements. Lack of standardisation could limit benefits from introducing WBCT in research and clinical practice because useful imaging information could become obscured. Measurements of bones and joints on WBCT are influenced by joint positioning and magnitude of loading, factors that need to be considered within a 3-D coordinate system. A proportion of WBCT studies examine inter- and intraobserver reproducibility for different radiological measurements in the knee or foot with reproducibility generally reported to be high. However, investigations of test-retest reproducibility are still lacking. Thus, the current ability to evaluate, e.g. the effects of surgery or structural disease progression, is questionable. This paper presents an overview of the relevant literature on WBCT in the lower extremity with an emphasis on factors that may affect measurement reproducibility in the foot/ankle and knee. We discuss the caveats of performing WBCT without consensus on imaging procedures and measurements.

Magnetic Resonance T2 * Is Increased in Patients With Early-Stage Achilles and Patellar Tendinopathy.

BACKGROUND: T2 * mapping has proven useful in tendon research and may have the ability to detect subtle changes at an early stage of tendinopathy. PURPOSE: To investigate the difference in T2 * between patients with early tendinopathy and healthy controls, and to investigate the relationship between T2 * and clinical outcomes, tendon size, and mechanical properties. STUDY TYPE: Prospective cross-sectional. SUBJECTS: Sixty-five patients with early tendinopathy and 25 healthy controls. FIELD STRENGTH/SEQUENCE: Three Tesla, ultrashort time to echo magnetic resonance imaging. ASSESSMENT: Tendon T2 * was quantified using a monoexponential fitting algorithm. Clinical symptoms were evaluated using the Victorian Institute of Sports Assessment-Achilles/Patella (VISA-A/VISA-P). In vivo mechanical properties were measured using an ultrasound-based method that determined force and deformation simultaneously in tendons of patellar tendinopathy patients. STATISTICAL TESTS: A generalized linear model adjusted for age was applied to investigate the difference between patients and controls. In the two patient groups, linear regressions were applied to investigate the association between T2 * and tendon size, clinical outcomes, and biomechanical properties. RESULTS: There was a significant difference in T2 * between patients and healthy controls (204.8 [95% CI: 44.5-365.0] µsec, P < 0.05). There was a positive correlation between tendon size and T2 * for both Achilles (r = 0.72; P < 0.05) and patellar tendons (r = 0.53; P < 0.05). There was no significant correlation between VISA-A and T2 * (r = -0.2; P = 0.17) or VISA-P and T2 * (r = -0.5; P = 0.0504). Lastly, there was a negative correlation between modulus and T2 * (r = -0.51; P < 0.05). DATA CONCLUSIONS: T2 * mapping can detect subtle structural changes that translate to altered mechanical properties in early-phase tendinopathy. However, T2 * did not correlate with clinical scores in patients with early-phase Achilles and patellar tendinopathy. Thus, T2 * mapping may serve as a tool for early detection of structural changes in tendinopathy but does not necessarily describe the clinical severity of disease. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 2.

Early development of tendinopathy in humans: Sequence of pathological changes in structure and tissue turnover signaling.

Overloading of tendon tissue with resulting chronic pain (tendinopathy) is a common disorder in occupational-, leisure- and sports-activity, but its pathogenesis remains poorly understood. To investigate the very early phase of tendinopathy, Achilles and patellar tendons were investigated in 200 physically active patients and 50 healthy control persons. Patients were divided into three groups: symptoms for 0-1 months (T1), 1-2 months (T2) or 2-3 months (T3). Tendinopathic Achilles tendon cross-sectional area determined by ultrasonography (US) was ~25% larger than in healthy control persons. Both Achilles and patellar anterior-posterior diameter were elevated in tendinopathy, and only later in Achilles was the width increased. Increased tendon size was accompanied by an increase in hypervascularization (US Doppler flow) without any change in mRNA for angiogenic factors. From patellar biopsies taken bilaterally, mRNA for most growth factors and tendon components remained unchanged (except for TGF-beta1 and substance-P) in early tendinopathy. Tendon stiffness remained unaltered over the first three months of tendinopathy and was similar to the asymptomatic contra-lateral tendon. In conclusion, this suggests that tendinopathy pathogenesis represents a disturbed tissue homeostasis with fluid accumulation. The disturbance is likely induced by repeated mechanical overloading rather than a partial rupture of the tendon.

Positional changes in lumbar disc herniation during standing or lumbar extension: a cross-sectional weight-bearing MRI study.

OBJECTIVES: To investigate biomechanical changes in lumbar disc herniations. METHODS: Patients with lumbar disc herniation verified on a 1.5-3-T magnetic resonance imaging (MRI) scanner were imaged in a weight-bearing 0.25-T MRI scanner in (1) standing position, (2) conventional supine position with relative lumbar flexion, and (3) supine position with a forced lumbar extension by adding a lumbar pillow. The L2-S1 lordosis angle, the disc cross-sectional area, the disc cross-sectional diameter, and the spinal canal cross-sectional diameter were measured for each position. Disc degeneration and nerve root compression were graded, and the pain intensity was reported during each scan position. RESULTS: Forty-three herniated discs in 37 patients (36.7 ± 11.9 years) were analyzed in each position. The L2-S1 lumbar angle increased in the standing position (mean difference [MD]: 5.61°, 95% confidence interval [95% CI]: 3.44 to 7.78) and with the lumbar pillow in the supine position (MD: 14.63°, 95% CI: 11.71 to 17.57), both compared with the conventional supine position. The herniated disc cross-sectional area and diameter increased during standing compared with during conventional supine position. No changes were found in the spinal canal cross-sectional diameter between positions. Higher nerve root compression grades for paracentral herniations were found during standing compared with during conventional supine position. This was neither found with a lumbar pillow nor for central herniations in any position compared with conventional supine. CONCLUSION: Disc herniations displayed dynamic behavior with morphological changes in the standing position, leading to higher nerve root compression grades for paracentral herniated discs. KEY POINTS: • Lumbar herniated discs increased in size in the axial plane during standing. • Increased nerve root compression grades for paracentral herniated discs were found during standing. • Weight-bearing MRI may increase the diagnostic sensitivity of nerve root compression in lumbar disc herniations.

Mechanical properties and UTE-T2* in Patellar tendinopathy: The effect of load magnitude in exercise-based treatment.

Loading intervention is currently the preferred management of tendinopathy, but to what extent different loading regimes influence the mechanical response in tendons is scarcely investigated. Therefore, the purposes of the investigation were to examine the effect of exercise interventions with either high or low load magnitude applied to the tendinopathic patellar tendon and the influence on its mechanical, material, and morphological properties. Forty-four men with chronic patellar tendinopathy were randomized to 12 weeks of exercising with either; 55% of 1RM throughout the period (MSR group) or 90% of 1RM (HSR group), and with equal total exercise volume in both groups. Mechanical (stiffness), material (T2* relaxation time), and morphological (cross-sectional area (CSA)) properties were assessed at baseline and after 12 weeks of intervention. MRI with ultra-short echo times (UTE) and T2*-mapping was applied to explore if T2* relaxation time could be used as a noninvasive marker for internal material alteration and early change thereof in response to intervention. There was no effect of HSR or MSR on the mechanical (stiffness), material (T2* relaxation time) or morphological (CSA) properties, but both regimes resulted in significant strength gain. In conclusion, there were no statistically superior effect of exercising with high (90%) compared to moderate (55%) load magnitude on the mechanical, material or morphological properties.

UTE T2* mapping of tendinopathic patellar tendons: an MRI reproducibility study.

BACKGROUND: There is currently a lack of imaging modalities that can be used as a sensitive measure in tendinopathy. Recent findings suggest the applicability of ultra-short echo time (UTE) magnetic resonance imaging (MRI) T2* mapping in tendons, but the reproducibility remains unknown. PURPOSE: To evaluate test-retest reproducibility of UTE MRI T2* mapping of tendinopathic patellar tendons and to evaluate the intra- and inter-observer reproducibility of the measurement. MATERIAL AND METHODS: Fifteen patients with chronic patellar tendinopathy were evaluated with UTE MRI twice in a 3.0-T scanner on the same day. Manual segmentation of the patellar tendon was performed by two blinded investigators and automated T2*map reconstruction was performed in custom-made software. RESULTS: There was a significant and numerically small difference in test-retest T2* values (T2*meandiff = 0.06 ± 0.07 ms ≈ 3.7%; P = 0.006) with an ICC = 0.91 (95% confidence interval [CI] 0.58-0.98; typical error of 3.0%). The intra- and inter-observer reproducibility showed no significant bias (P = 0.493 and P = 0.052), and generally substantial reproducibility was demonstrated for T2* (intra-observer ICC = 0.99; 95% CI 0.98-1.00 and inter-observer ICC = 0.99; 95% CI 0.96-1.00, and typical error 1.3% and 1.3%, respectively). CONCLUSION: These data demonstrate a small bias between repeated measurements for UTE T2*, but with a very low associated mean difference (3.7%) between the two tests. The high ICC values and low typical error % demonstrate reproducibility of repeated T2*-mapping sessions. Further, the method showed substantial intra- and inter-observer reproducibility for T2* values proving feasibility for use of UTE T2* mapping in research and clinical practice.

Weight-bearing MRI of the Lumbar Spine: Spinal Stenosis and Spondylolisthesis.

Symptoms of degenerative lumbar spinal stenosis include back pain, radiculopathy, claudication, and muscular fatigue that tend to be predominant in the standing position or during walking. Lumbar spondylolisthesis is also a well-known cause of spinal stenosis, lateral recess, and neural foraminal narrowing that tends to become more severe in the upright position. This indicates a functional positional component of both spinal stenosis and spondylolisthesis. Lumbar spinal stenosis and spondylolisthesis are typically evaluated by magnetic resonance imaging (MRI) performed in the supine position with a pillow under the patient's lower limbs that slightly flexes the lumbar spine and ameliorates symptoms. Because these two entities tend to be aggravated in the upright position, it seems rational to also consider performing diagnostic imaging in these patients in the upright position. This article reviews the use of weight-bearing MRI for lumbar spinal stenosis and spondylolisthesis.

Weight-bearing MRI of the Lumbar Spine: Technical Aspects.

Magnetic resonance imaging (MRI) has an established role in the assessment of degenerative musculoskeletal conditions. However, conventional supine MRI findings often correlate poorly with clinical findings. Some patients experience accentuated back pain in the weight-bearing position. Therefore, supine MRI may underestimate the severity of degenerative spine findings. To try and improve the clinical validity of spine imaging, axial loading devices have been used with conventional supine MR imaging to simulate loading of the upright spine. More recently, upright weight-bearing MRI systems (0.25-0.6 T) were introduced, allowing images to be obtained in the standing or seated weight-bearing position and even during upright flexion or extension, rotation, or bending. Some scanners even enable capturing of real-time spinal movement. This review addresses the technical aspects and potential challenges of weight-bearing MRI, both in clinical practice and research.

Single- vs. double-dose gadolinium contrast in delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) in knee osteoarthritis: is dose reduction possible on 3-T MRI?

BACKGROUND: Reduction in gadolinium (Gd) contrast agents is wanted due to the uncertainty of the potential side effects. PURPOSE: To investigate whether it is possible to reduce the contrast dose from conventional double dose to single dose when increasing the field strength from 1.5-T to 3-T for separating early cartilage degeneration from healthy cartilage, assessed by delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC). MATERIAL AND METHODS: Nine patients with knee osteoarthritis (OA), Kellgren-Lawrence grade (KLG) 1-4, were recruited from an ongoing weight loss cohort study. dGEMRIC was performed at 3-T using single (0.1 mmoI/kg) and double (0.2 mmoI/kg) doses of intravenous (i.v.) Gd-DTPA2-. Regions of interest (ROls) were drawn around the posterior weight-bearing femoral knee cartilage in lateral and medial compartments. In five medial compartments ROIs could not be drawn due to severe degeneration of cartilage. T1-relaxation times were compared to previously published values from 1.5-T and to non-contrast values from 3-T. RESULTS: Mean dGEMRIC T1-relaxation time in the lateral compartment was 769 ms for single dose vs. 561 ms for double dose ( P < 0.0001); and 685 ms for single dose vs. 454 ms for double dose ( P = 0.004) in the medial compartment. CONCLUSION: We found a dose-response relationship between single and double doses of Gd-DTPA2- using 3-T in knee OA patients, similar to the findings at 1.5-T. Compared to the T1-relaxation time at 3-T without contrast (1240 ms), this further separation between OA and normal cartilage indicates that "single dose" dGEMRIC could be sufficient for cartilage health assessment at 3-T.

Reliability of standing weight-bearing (0.25T) MR imaging findings and positional changes in the lumbar spine.

OBJECTIVE: To test the reliability and absolute agreement of common degenerative findings in standing positional magnetic resonance imaging (pMRI). METHODS AND MATERIALS: Low back pain patients with and without sciatica were consecutively enrolled to undergo a supine and standing pMRI. Three readers independently evaluated the standing pMRI for herniation, spinal stenosis, spondylolisthesis, HIZ lesions and facet joint effusion. The evaluation included a semi-quantitative grading of spinal stenosis, foraminal stenosis and spinal nerve root compression. The standing pMRI images were evaluated with full access to supine MRI. In case lower grades or the degenerative findings were not present in the supine images, this was reported separately as position-dependent changes. A subsample of 20 pMRI examinations was reevaluated after two months. The reproducibility was assessed by inter- and intra-reader reliability (kappa statistic) and absolute agreement between readers. RESULTS: Fifty-six patients were included in this study. There was fair-to-substantial inter-reader reliability (κ 0.47 to 0.82) and high absolute agreement (72.3% to 99.1%) for the pMRI findings. The intra-reader assessment showed similar reliability and agreement (κ 0.36 to 0.85; absolute agreement: 62.5% to 98.8%). Positional changes between the supine and standing position showed a fair-to-moderate inter- and intra-reader reliability (κ 0.25 to 0.52; absolute agreement: 97.0% to 99.1). CONCLUSION: Evaluation of the lumbar spine for degenerative findings by standing pMRI has acceptable reproducibility; however, positional changes from the supine to the standing position as an independent outcome should be interpreted with caution because of lower reliability, which calls for further standardisation.

The role of ultrasound in diagnosing rheumatoid arthritis, what do we know? An updated review.

To clarify if musculoskeletal ultrasound (MSUS) improves early diagnosis of RA when added to the clinical examination of patients with possible arthritis. We performed a systematic literature review of original studies dealing with the value of MSUS in the early diagnosis of RA. Studies were identified using the databases of PubMed, EMBASE and Cochrane library. Only studies in English investigating populations with non-classified arthritis or arthralgia were included. Fifteen original studies investigating the added value of MSUS in diagnosing RA were identified. They differed in sample size, study population, serology status, number of joints investigated and regarding the ultrasound machines and probes used. Thirteen out of 15 studies concluded that use of MSUS had an added value compared to clinical examination and laboratory evaluation alone for diagnosing RA. One study found that MSUS did not add substantial discriminatory value for predicting RA in an early arthritis cohort when added to routine assessment. However, in this study only 16 joints were examined (wrists and MTP 3-5 were not included). One study investigated only seropositive patients and found no significant advantage of MSUS on patient level although a trend was noted. Accordingly, two other studies found MSUS to be useful especially in seronegative patients. The use of MSUS adds value in diagnosing early RA, especially in seronegative arthritis. However, no study to date has documented any effect of DMARD initiation based on MSUS findings (subclinical arthritis) alone. More studies investigating this matter are warranted.

Navicular bone position determined by positional MRI: a reproducibility study.

OBJECTIVE: To examine intraobserver, interobserver and between-day reproducibility of positional MRI for evaluation of navicular bone height (NVH) and medial navicular position (MNP). MATERIALS AND METHODS: Positional MRI (pMRI) of the foot was performed on ten healthy participants (0.25 T G-scanner). Scanning was performed in supine and standing position, respectively. Two radiologists evaluated the images in a blinded manner. Reliability and agreement were assessed by calculation of intraclass correlation coefficient (ICC) and 95 % limits of agreement as a percentage of the mean (LOA%). RESULTS: Intraobserver and interobserver reliability was "substantial" in both supine and standing position (ICC 0.86-0.98) and showed good agreement (LOA% 4.9-14.7 %). Between-day reliability of navicular height and medial navicular position in standing position remained substantial (ICC 0.85-0.92) with adequate agreement (LOA% 8.3-19.8 %). In supine position between-day reliability was "moderate" for NVH (ICC 0.72) and "slight" for MNP (ICC 0.39). Agreement remained adequate between-days for MNP in supine position (LOA% 17.7 %), but it was less than adequate for NVH in supine position (LOA% 24.2 %). CONCLUSION: Navicular height and medial navicular position can be measured by pMRI in a very reproducible manner within and between observers. Increased measurement variation is observed between-days in supine position, which may be due to small positional differences or other unknown biomechanical factors.

Association between tobacco smoking and response to tumour necrosis factor α inhibitor treatment in psoriatic arthritis: results from the DANBIO registry.

OBJECTIVES: To investigate the association between tobacco smoking and disease activity, treatment adherence and treatment responses among patients with psoriatic arthritis (PsA) initiating the first tumour necrosis factor α inhibitor therapy (TNFi) in routine care. METHODS: Observational cohort study based on the Danish nationwide DANBIO registry. Kaplan-Meier plots, logistic and Cox regression analyses by smoking status (current/previous/never smoker) were calculated for treatment adherence, ACR20/50/70-responses and EULAR-good-response. Additional stratified analyses were performed according to gender and TNFi-subtype (adalimumab/etanercept/infliximab). RESULTS: Among 1388 PsA patients included in the study, 1148 (83%) had known smoking status (33% current, 41% never and 26% previous smokers). Median follow-up time was 1.22 years (IQR 0.44-2.96). At baseline, current smokers had lower Body Mass Index (27 kg/m(2) (23-30)/28 kg/m(2) (24-31)) (median (IQR)), shorter disease duration (3 years (1-8)/5 years (2-10)), lower swollen joint count (2 (0-5)/3 (1-6)), higher visual-analogue-scale (VAS) patient global (72 mm (54-87)/68 mm (50-80)), VAS fatigue (72 mm (51-86)/63 mm (40-77)) and Health Assessment Questionnaire (HAQ) score (1.1 (0.7 to 1.5)/1.0 (0.5 to 1.5)) than never smokers (all p<0.05). Current smokers had shorter treatment adherence than never smokers (1.56 years (0.97 to 2.15)/2.43 years (1.88 to 2.97), (median (95% CI)), log rank p=0.02) and poorer 6 months' EULAR-good-response rates (23%/34%), ACR20 (24%/33%) and ACR50 response rates (17%/24%) (all p<0.05), most pronounced in men. In current smokers, the treatment adherence was poorer for infliximab (HR) 1.62, 95% CI 1.06 to 2.48) and etanercept (HR 1.74, 1.14 to 2.66) compared to never smokers, but not for adalimumab (HR 0.80, 0.52 to 1.23). CONCLUSION: In PsA, smokers had worse baseline patient-reported outcomes, shorter treatment adherence and poorer response to TNFi's compared to non-smokers. This was most pronounced in men and in patients treated with infliximab or etanercept.

Validation of a novel ultrasound measurement of achilles tendon length.

PURPOSE: A clinically applicable and accurate method for measuring Achilles tendon length is needed to investigate the influence of elongation of the Achilles tendon after acute rupture. The purpose of this study was to develop and validate an ultrasonographic (US) length measurement of the Achilles tendon-aponeurosis complex. METHODS: Both legs of 19 non-injured subjects were examined by magnetic resonance imaging (MRI) and US. The length from calcaneus to the medial head of m. Gastrocnemius was measured by three independent US examiners. Repeated US measurements were performed and compared to MRI measurements. Intra-rater and inter-rater reliability and the agreement between MRI and US were determined. Data were evaluated using the intraclass correlation coefficient (ICC), the standard error of the measurement (SEM) and the minimal detectable change (MDC). RESULTS: Intra-rater reliability of US assessment showed no significant differences between test days: ICC 0.96, SEM 4 mm and MDC 10 mm. Inter-rater reliability showed a systematic difference between US observers of 2-5 mm (p = 0.001-0.036); ICC 0.97, SEM 3 mm and MDC 9 mm. MRI measurements were on average 4 mm longer than US (p = 0.001). CONCLUSION: The novel ultrasound measurement showed good reliability and accuracy. For comparison between groups of non-injured subjects differences of more than 4 mm can be detected. For repeated assessment of individual subjects differences of more than 10 mm can be detected. The measurement needs to be further assessed in the setting of acute Achilles tendon rupture. CLINICAL RELEVANCE: This new ultrasound measurement might allow for length measurement of ruptured Achilles tendons in the acute and chronic state after rupture. LEVEL OF EVIDENCE: II.

Detection of Interstitial Lung Disease in Rheumatoid Arthritis by Thoracic Ultrasound: A Diagnostic Test Accuracy Study.

OBJECTIVE: To determine the diagnostic accuracy of thoracic ultrasound (TUS) for detecting interstitial lung disease (ILD) in rheumatoid arthritis (RA) with respiratory symptoms. METHODS: Individuals with RA visiting rheumatologic outpatient clinics in the Region of Southern Denmark were systematically screened for dyspnea, cough, recurrent pneumonia, prior severe pneumonia, or a chest x-ray indicating interstitial abnormalities. Eighty participants with a positive screening were consecutively included. Individuals were not eligible if they had a chest high-resolution computed tomography (HRCT) less than 12 months ago or were already diagnosed with ILD. A blinded TUS expert evaluated TUS, and TUS was registered as positive for ILD if at least 10 B-lines or bilateral thickened and fragmented pleura were present. The primary outcomes were TUS's sensitivity, specificity, and positive predictive value and negative predictive value. An ILD-specialized thoracic radiologist assessed HRCT, followed by a multidisciplinary team discussion, which was the reference standard. The accepted window of HRCT was less than 30 days after TUS was performed. RESULTS: A total of 77 participants received HRCT less than 30 days after TUS, and 23 (30%) were diagnosed with ILD. TUS had a sensitivity of 82.6% (95% confidence interval [CI] 61.2%-95.0%) and a specificity of 51.9% (95% CI 37.8%-65.7%), corresponding to a positive predictive value of 42.2% (95% CI 27.7%-57.8%) and a negative predictive value of 87.5% (95% CI 71.0%-96.5%). CONCLUSION: To our knowledge, this prospective study is the first to use respiratory symptoms in RA as inclusion criteria. Systematic screening for respiratory symptoms combined with TUS can reduce the diagnostic delay of ILD in RA.