A validation of register-derived diagnoses of interstitial lung disease in patients with inflammatory arthritis: data from the NOR-DMARD study

OBJECTIVE There is a lack of knowledge concerning the validity of the interstitial lung disease (ILD) diagnoses used in epidemiological studies on rheumatic diseases. This paper seeks to verify register-derived ILD diagnoses using chest computed tomography (CT) and medical records as a gold standard. METHOD The Norwegian Anti-Rheumatic Drug Register (NOR-DMARD) is a multicentre prospective observational study of patients with inflammatory arthritis who start treatment with disease-modifying anti-rheumatic drugs. NOR-DMARD is linked to the Norwegian Patient Registry (NPR) and Cause of Death Registry. We searched registers for ILD coded by ICD-10 J84 or J99 among patients with rheumatoid arthritis, psoriatic arthritis, or spondyloarthritis. We extracted chest CT reports and medical records from participating hospitals. Two expert thoracic radiologists scored examinations to confirm the ILD diagnosis. We also searched medical records to find justifications for the diagnosis following multidisciplinary evaluations. We calculated the positive predictive values (PPVs) for ILD across subsets. RESULTS We identified 71 cases with an ILD diagnosis. CT examinations were available in 65/71 patients (91.5%), of whom ILD was confirmed on CT in 29/65 (44.6%). In a further 10 patients, medical records confirmed the diagnosis, giving a total of 39/71 verified cases. The PPV of a register-derived ILD diagnosis was thus 54.9%. In a subset of patients who had received an ILD code at two or more time-points and had a CT scan taken within a relevant period, the PPV was 72.2%. CONCLUSION The validity of register-based diagnoses of ILD must be carefully considered in epidemiological studies

Differences and similarities between the EULAR/ASAS-EULAR and national recommendations for treatment of patients with psoriatic arthritis and axial spondyloarthritis across Europe

This is the first report comparing EULAR and national treatment recommendations for PsA patients across Europe, and the first this decade to compare ASAS-EULAR and national treatment recommendations in axSpA patients. An electronic survey was completed from October 2021–April 2022 by rheumatologists in 15 European countries. One and four countries followed all EULAR and ASAS-EULAR recommendations, respectively. Five countries had no national treatment recommendations for PsA and/or axSpA, but followed other regulations. In several countries, national treatment recommendations predated the most recent EULAR/ASAS-EULAR recommendations. Entry criteria for starting biologic/targeted synthetic disease-modifying anti-rheumatic drugs varied considerably. In several countries, for PsA patients with significant skin involvement, interleukin-17 inhibitors were not given preference. The positioning of Janus Kinase inhibitors differed and Phosphodiesterase-4 inhibitors were not in use/reimbursed in most countries. This study may motivate European countries to update their national treatment recommendations, to align them better with the latest international recommendations

Impact of discordance between patient's and evaluator's global assessment on treatment outcomes in 14 868 patients with spondyloarthritis

Funding: This work was supported by Novartis. Novartis had no influence on the data collection, statistical analyses, manuscript preparation or decision to submit.Peer reviewedPostprintPostprintPostprintPostprin

A real-time system for biomechanical analysis of human movement and muscle function

Mechanical analysis of movement plays an important role in clinical management of neurological and orthopedic conditions. There has been increasing interest in performing movement analysis in real-time, to provide immediate feedback to both therapist and patient. However, such work to date has been limited to single-joint kinematics and kinetics. Here we present a software system, named human body model (HBM), to compute joint kinematics and kinetics for a full body model with 44 degrees of freedom, in real-time, and to estimate length changes and forces in 300 muscle elements. HBM was used to analyze lower extremity function during gait in 12 able-bodied subjects. Processing speed exceeded 120 samples per second on standard PC hardware. Joint angles and moments were consistent within the group, and consistent with other studies in the literature. Estimated muscle force patterns were consistent among subjects and agreed qualitatively with electromyography, to the extent that can be expected from a biomechanical model. The real-time analysis was integrated into the D-Flow system for development of custom real-time feedback applications and into the gait real-time analysis interactive lab system for gait analysis and gait retraining. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11517-013-1076-z) contains supplementary material, which is available to authorized users

Comparative effectiveness of subcutaneous tocilizumab versus intravenous tocilizumab in a pan-European collaboration of registries

Objective To compare the real-word effectiveness of subcutaneous tocilizumab (TCZ-SC) and intravenous tocilizumab (TCZ-IV) in rheumatoid arthritis (RA). Methods Patients with RA with TCZ from eight European registries were included. Drug retention was compared using unadjusted Kaplan-Meier and Cox models adjusted for baseline patient, disease and treatment characteristics, using a strata term for year of treatment initiation and country of registry. The proportions of patients achieving Clinical Disease Activity Index (CDAI) remission and low disease activity (LDA) at 1 year were compared using samples matched on the same covariates and corrected for attrition using LUNDEX. Results 3448 patients were retrieved, 2414 with TCZ-IV and 1034 with TCZ-SC. Crude median retention was 3.52 years (95% CI 3.22 to 3.85) for TCZ-IV and 2.12 years for TCZ-SC (95% CI 1.88 to 2.38). In a country-stratified and year of treatment initiation-stratified, covariate-adjusted analysis, hazards of discontinuation were similar between TCZ-SC and TCZ-IV treated patients (HR 0.93, 95% CI 0.80 to 1.09). The average adjusted CDAI change at 1 year was similar in both groups (-6.08). After matching, with 560 patients in each group, CDAI remission corrected for attrition at 1 year was also similar between TCZ-SC and TCZ-IV (10.4% in TCZ-IV vs 12.8% in TCZ-SC (difference: 2.4%, bootstrap 95% CI -2.1% to 7.6%)), but CDAI LDA was lower in TCZ-IV patients: 41.0% in TCZ-IV versus 49.1% in TCZ-SC (difference: 8.0 %; bootstrap 95% CI 2.4% to 12.4%). Conclusion With similar retention and effectiveness, TCZ-SC is an adequate alternative to TCZ-IV for RA. When possible, considering the costs of the TCZ-IV route, TCZ-SC should be the preferred mode of administration.Peer reviewe

Synthesis, Biological Investigation, and Structural Revision of Sielboldianin A

The two <i>ar</i>-bisabol sesquiterpenoids (+)-sielboldianin A (<b>1</b>) and (+)-sielboldianin B (<b>2</b>) were isolated from the stem bark of the plant <i>Fraxinus sielboldiana</i> and belong to a medicinally interesting class of natural products used in traditional Chinese medicine. Herein the total synthesis of the proposed structure of (+)-sielboldianin A (<b>1</b>) is reported using an organocatalyzed enantioselective bromolactonization protocol. X-ray analysis of a key intermediate together with specific rotation values and NOESY data of the synthesized product enabled the revision of the absolute configuration of the natural product (+)-sielboldianin A to (7<i>R</i>,10<i>R</i>). Studies on the antioxidant effects using two cell-based assays were conducted. These studies revealed that the enantiomer of <b>1</b> exhibited antioxidant effects with IC₅₀ values of 18 ± 3 μM in a cellular lipid peroxidation antioxidant activity assay. Moreover, (−)-<b>1</b> showed strong protective effects against reactive oxygen species in a cell-based antioxidant activity assay (IC₅₀ = 31 ± 5 μM). In addition, the two <i>ar</i>-sesquiterpenoids (−)-boivinianin B and (−)-gossoronol showed no effect in either assay. No cytotoxic activity in the K562 cancer cell line was observed for the three sesquiterpenoids tested (IC₅₀ > 50 μM)