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To evaluate whether disease activity-guided tapering of biologics compared to continuation as usual care enables a substantial dose reduction while disease activity remains equivalent. In this pragmatic, randomized, open-label, equivalence trial, adults with rheumatoid arthritis, psoriatic arthritis, or axial spondyloarthritis in low disease activity on stable-dose biologics for ≥ 12 months were randomized 2:1 into either the tapering group, i.e. disease activity-guided prolongation of the biologic dosing interval until flare or withdrawal, or the control group, i.e. maintaince of baseline biologics with a possible small interval increase at the patients request. The co-primary outcome in the intention-to-treat population was met if superiority in ≥ 50% biologic reduction at 18 months was demonstrated and disease activity was equivalent (equivalence margins ± 0.5). Ninety-five patients were randomized to tapering and 47 to control, of whom 37% (35/95) versus 2% (1/47) achieved ≥ 50% biologic reduction at 18 months. The risk difference was statistically significant [35%, 95% confidence interval (CI) 24%–45%], while disease activity remained equivalent [mean difference 0.05, 95% CI −0.12–0.29]. A statistically significant flare risk was observed [tapering 41% (39/95) vs control 21% (10/47), risk difference 20%, 95% CI 4%–35%]; but, only 1% (1/95) and 6% (3/47) had persistent flare and needed to switch to another biological drug. Disease activity-guided tapering of biologics in patients with inflammatory arthritis enabled one-third to achieve ≥ 50% biologic reduction, while disease activity between groups remained equivalent. Flares were more frequent in the tapering group but were managed with rescue therapy. [ABSTRACT FROM AUTHOR]

Objectives: In Denmark, patients with inflammatory arthritis (IA) have completed patient-reported outcome measures (PROMs) via touchscreens in the outpatient clinic since 2006. However, current technology makes it possible for patients to use their own smartphone via an application (app) developed for the Danish Rheumatology Database (DANBIO). This study aims to evaluate the agreement of PROMs between the DANBIO app and outpatient touchscreen in patients with IA.Method: Patients with IA (rheumatoid arthritis, psoriatic arthritis, and axial spondyloarthritis) were enrolled in a randomized, crossover, agreement study. Participants answered PROMs through the two device types in a randomized order. Differences in PROM scores with 95% confidence intervals (CIs) were evaluated for similarity according to prespecified equivalence margins.Results: The touchscreen invitation was accepted by 138 patients. Sixty patients (20 with each diagnosis) were included. The difference in Health Assessment Questionnaire Disability Index between the two device types was -0.007 (95% CI -0.043 to 0.030); thus, equivalence was demonstrated. In addition, all other PROMs obtained with the two device types were equivalent, except for the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), which was within the limits of minimally clinically important difference (MCID). In total, 78.3% preferred the DANBIO app.Conclusion: In patients with IA, equivalence was demonstrated between two device types for all PROMs except BASDAI; however, BASDAI was within the limits of the MCID. Implementation of the DANBIO app is expected to optimize outpatient visits, thereby improving healthcare for the individual patient and society. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to examine anatomical variables of the lower cervical spine facet joints with regard to age, gender, and exposure to trauma. Methods: The lower four cervical spine segments (C4-C7 included) were obtained from 40 subjects during autopsy: 12 females and 28 males (median age 35 years, range 20-49). Through an available 636 unique facets (318 joints), 1830 randomly obtained observation lines were defined. Each of these lines resembled a 3-mm-thick parasaggital slice through a facet from which 10-µm-thick histological sections were produced and evaluated microscopically. Inter- and intraobserver agreement was tested on four randomly selected facets from each subject. Results: Significant age-, gender-, and trauma-related changes in the bone, cartilage, and soft tissues were observed, including subchondral sclerosis, fibrillation and splitting of cartilage, and cartilage length differences. Females were less affected by changes in the cartilage than males. Two synovial folds were present in all but one joint. Moderate interobserver and good intraobserver agreement were achieved. Conclusions: This study provides knowledge of the anatomy of the cervical spine facet joints. The findings support existing knowledge that males are more commonly affected by degenerative changes than females and that these changes are common from a young age. Histomorphometry confirms the presence of synovial folds in all of the facet joints. Following spinal trauma, pathological lesions may be produced in the facet joints and/or accentuate already existing pathology. The information provided in this study may have relevance for patients with neck pain. [ABSTRACT FROM AUTHOR]

The cervical spine facet joints have a central role in chronic pain syndromes following whiplash injuries. In order to improve our understanding of these pain syndromes, a detailed knowledge of the cervical spine anatomy and morphology is needed. Hence, a detailed examination of the cervical spine articular structures is needed and for this purpose we present a specialized histological method that may be employed in post-mortem studies. [ABSTRACT FROM AUTHOR]

To evaluate tumour necrosis factor inhibitor (TNFi) drug-levels and presence of anti-drug antibodies (ADAb) in patients with inflammatory arthritis who taper TNFi compared to TNFi continuation. Patients with rheumatoid arthritis, psoriatic arthritis, or axial spondyloarthritis on stable TNFi dose and in low disease activity ≥ 12 months were randomised (2:1) to disease activity-guided tapering or control. Blood samples at baseline, 12- and 18-months were evaluated for TNFi drug-levels and ADAb. In total, 129 patients were randomised to tapering (n = 88) or control (n = 41). Between baseline and month 18, a significant shift in TNFi drug-levels were observed in the tapering group resulting in fewer patients with high drug-levels (change: - 14% [95% CI - 27 to - 1%]) and more with low drug-levels (change: 18% [95% CI 5-31%]). Disease activity was equivalent between groups at 18 months, mean difference: RA - 0.06 (95% CI - 0.44 to 0.33), PsA 0.03 (95% CI - 0.36 to 0.42), and axSpA 0.16 (- 0.17 to 0.49), equivalence margins ± 0.5 disease activity points. ADAb were detected in eight patients, all from the tapering group. TNFi drug-level category or ADAb were not predictive for achieving successful tapering at 18 months. TNFi drug-levels decreased during tapering which indicate adherence to the tapering algorithm. Despite the difference in TNFi drug-levels at 18 months, disease activity remained equivalent, and only few tapering patients had detectable ADAb. These data do not support using TNFi drug-level and/or ADAb to guide the tapering decision but future research with larger trials is needed.Trial registration: EudraCT: 2017-001970-41, December 21, 2017., (© 2024. The Author(s).)

This review presents a simplified model to understand better how disease-modifying anti-inflammatory drugs (DMAIDs) work in immune-mediated inflammatory diseases (IMIDs) with a focus on rheumatology, dermatology, and gastroenterology. In this model, IMIDs are listed on a spectrum from autoinflammatory to autoimmune characterised by the involvement of either mostly the innate or the adaptive immune system. DMAIDs specifically target these immune components and have shown efficacy in distinct IMIDs. DMAID classes include TNF blockers, IL-1 blockers, IL-6 receptor blockers, IL-17 blockers, IL-23 blockers, and janus kinase inhibitors., (Published under Open Access CC-BY-NC-BD 4.0. https://creativecommons.org/licenses/by-nc-nd/4.0/.)

Background: Osteoporosis is significantly associated with fractures and burdens the health of especially older people. Osteoporotic fractures cause pain, disability, and increased mortality. Early diagnosis of osteoporosis allows earlier initiation of treatment, thereby reducing the risk of osteoporotic fractures. Chiropractors encounter potential osteoporotic patients daily, and perform radiological evaluation of these and other patients, including evaluation of X-rays done for other purposes than osteoporosis. Therefore, chiropractors may identify vertebral fractures, vertebral deformity or osteopenia not otherwise suspected or recorded., Methods: This study examines procedures available to the chiropractor to describe conventional X-rays with the focus of osteoporosis related findings. We review the indications for radiological examination in chiropractic practice, and in the realm of osteoporosis we describe radiological methods available for examination of conventional radiographs, and the necessity of inter-disciplinary communication., Results: National guidelines are available regarding referral for X-rays in chiropractic practice. Standardized protocols ensure image acquisition of the highest quality in the chiropractors' radiological department. Conventional X-ray examination is not indicated on clinical suspicion of osteoporosis alone, as bone mineral density testing is the diagnostic test. Radiological assessment of all available X-rays of patients above the age of 50 years should include evaluation of the bone quality, and hip and vertebral fracture assessment. The Singh index, Genant Semi-Quantitative tool (GSQ), and Algorithm-Based Qualitative method (ABQ) should be used consistently during interpretation. Referral for additional imaging and evaluation should be prompt and systematic when needed., Conclusions: This article presents an overview of evidence-based radiological procedures for the purpose of promoting early diagnosis of osteoporosis. We present recommendations to the clinicians where we propose an opportunistic evaluation of X-rays, done for any reason, which include systematic evaluation of bone quality, presence of hip and vertebral fractures, and vertebral deformation of all patients above the age of 50 years. Detailed referral to healthcare professionals for further diagnostic evaluation is performed when needed. Consistent, high-quality radiological procedures in chiropractic practices could feasibly contribute to the timely diagnosis of osteoporosis, ultimately minimizing the impact of osteoporosis-related complications on patients' health., (© 2024. The Author(s).)

Aims: To evaluate predictors for successful biologic tapering among patients with inflammatory arthritis using baseline characteristics from the BIODOPT trial., Methods: Adult patients with rheumatoid arthritis, psoriatic arthritis or axial spondyloarthritis on stable biologic dose and in low disease activity ≥12 months were enrolled. Participants were randomized (2:1) to disease activity-guided biologic tapering or continuation of baseline biologic. Patients achieving successful tapering reduced their biologic dose by ≥50%, had no protocol deviations and were in low disease activity at 18 months. Modified Poisson regression with robust variance estimator was applied., Results: In total, 142 patients were randomized to tapering (n = 95) or control (n = 47). Successful tapering was achieved by 32 and 2%, respectively. Tapering group was the only statistically significant independent predictor for successful tapering, risk ratio (RR): 14.0 (95% confidence interval [CI]: 1.9 to 101.3, P = .009). However, higher Short Form Health Survey 36 mental component summary (SF-36 MCS) was observed to be a predictor of potential importance, RR: 1.06 (95% CI: 0.99 to 1.13, P = .097). When limiting the analyses to the tapering group only, none of the baseline variables were statistically significant independent predictors but SF-36 MCS was still considered to be of potential importance, RR: 1.05 (95% CI: 0.99 to 1.12, P = .098)., Conclusion: Successful tapering is a reachable target for 1 in 3 patients with inflammatory arthritis who are interested in reducing their biological therapy. No statistically significant predictors (besides allocation to tapering) were identified. Future research on mental health and tapering is encouraged., (© 2023 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Background: The optimal first-line treatment in early rheumatoid arthritis (RA) is debated. We compared clinical and radiographic outcomes of active conventional therapy with each of three biological treatments with different modes of action., Methods: Investigator-initiated, randomised, blinded-assessor study. Patients with treatment-naïve early RA with moderate-severe disease activity were randomised 1:1:1:1 to methotrexate combined with (1) active conventional therapy: oral prednisolone (tapered quickly, discontinued at week 36) or sulfasalazine, hydroxychloroquine and intra-articular glucocorticoid injections in swollen joints; (2) certolizumab pegol; (3) abatacept or (4) tocilizumab. Coprimary endpoints were week 48 Clinical Disease Activity Index (CDAI) remission (CDAI ≤2.8) and change in radiographic van der Heijde-modified Sharp Score, estimated using logistic regression and analysis of covariance, adjusted for sex, anticitrullinated protein antibody status and country. Bonferroni's and Dunnet's procedures adjusted for multiple testing (significance level: 0.025)., Results: Eight hundred and twelve patients were randomised. Adjusted CDAI remission rates at week 48 were: 59.3% (abatacept), 52.3% (certolizumab), 51.9% (tocilizumab) and 39.2% (active conventional therapy). Compared with active conventional therapy, CDAI remission rates were significantly higher for abatacept (adjusted difference +20.1%, p<0.001) and certolizumab (+13.1%, p=0.021), but not for tocilizumab (+12.7%, p=0.030). Key secondary clinical outcomes were consistently better in biological groups. Radiographic progression was low, without group differences.The proportions of patients with serious adverse events were abatacept, 8.3%; certolizumab, 12.4%; tocilizumab, 9.2%; and active conventional therapy, 10.7%., Conclusions: Compared with active conventional therapy, clinical remission rates were superior for abatacept and certolizumab pegol, but not for tocilizumab. Radiographic progression was low and similar between treatments., Trial Registration Number: NCT01491815., Competing Interests: Competing interests: MØ received the study drug from BMS and UCB; research grants from Abbvie, BMS, Merck, Novartis and UCB; speaker fees from Abbvie, BMS, Celgene, Eli-Lilly, Galapagos, Gilead, Janssen, MEDAC, Merck, Novartis, Pfizer, Sandoz, and UCB; and consultancy fees from Abbvie, BMS, Celgene, Eli-Lilly, Galapagos, Gilead, Janssen, MEDAC, Merck, Novartis, Pfizer, Sandoz and UCB. RFvV received the study drug from BMS and UCB; research grants from BMS, GSK, UCB and AstraZeneca; consulting fees from AbbVie, AstraZeneca, Biogen, BMS, Galapagos, Janssen, Miltenyi, Pfizer and UCB; expert fees from AbbVie, Galapagos, GSK, Janssen, Pfizer, R-Pharma and UCB; and advisory board fees from AbbVie, AstraZeneca, Biogen, BMS, Galapagos, Janssen, Miltenyi, Pfizer and UCB. MLH received research grants from AbbVie, Biogen, BMS, Celtrion, Eli Lily, Janssen Biologics B.V., Lundbeck Foundation, MSD, Pfizer, Roche, Samsung Biopies, Sandoz and Novartis; and institution pay from Pfizer, Medac, AbbVie and Sandoz; chaired the steering committee of the Danish Rheumatology Quality Registry (DANBIO), which receives public funding from the hospital owners and funding from pharmaceutical companies; cochairs EuroSpA, which generates real-world evidence of treatment of psoriatic arthritis and axial spondylorthritis based on secondary data and is partly funded by Novartis. DCN received consulting fees from AbbVie, BMS, Lilly, MSD, Novartis, Pfizer, Roche and UCB' meeting support from Pfizer; advisory board participation fee from Novartis; and other service fee by BMS. MTN received research grants from AbbVie, BMS, Pfizer, Galapagos, Amgen and Eli Lily. BG received consulting fee from Novartis and honorary lecture payment from Novartis and Nordic-Pharma. IG received royalty fee for book authorship and support for attending meetings by EULAR. DG received advisory board fee from Eli Lily and AbbVie and speakers fee from Eli Lily. A-BA received speakers fee from AbbVie, Eli Lily, Novartis and Pfizer. CG received the study drug from BMS and UCB. MKL received advisory board fee from AbbVie. AS received advisory board fee from GSK (institution pay). LU received speakers fee from Janssen and support for meeting/travel from AbbVie and Eli Lily. DJS received honorarium fee from UCB (not a part of this, unrelated medication). GB received consultancy fee from UCB. ICO received research grants from EU Horizon 2020 and EU Horizon Europe, advisory board participation from IMPRESS-Norway, ALPHA2PREVENT, FLECAPRO and EVOLVD, and meeting/travel support from European Clinical Research Infrastructure Network. The remaining authors declared no disclosures., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Whiplash injuries are common in Denmark affecting around 16,000 new patients annually. Approximately 50% of the casualties develop chronic symptoms and 10% become disabled. Many of these patients will have contact to the healthcare system, and there is a need for structured and knowledge-based examination, diagnosis and recording of findings in all clinical settings. This review discusses which variables should be recorded in clinical practice, in order to establish the best possible foundation for a structured individualized treatment protocol of the whiplash patient.

Objective: To evaluate flare risk when tapering or withdrawing biologic or targeted synthetic DMARDs (bDMARDs or tsDMARDs) compared with continuation in patients with inflammatory arthritis in sustained remission or with low disease activity., Methods: Articles were identified in the Cochrane Library, PubMed, Embase and Web of Science. Eligible trials were randomized controlled trials comparing tapering and/or withdrawal of bDMARDs and/or tsDMARDs with the standard dose in inflammatory arthritis. Random effects meta-analysis was performed with risk ratio (RR) or Peto's odds ratio (POR) for sparse events and 95% CI., Results: The meta-analysis comprised 22 trials: 11 assessed tapering and 7 addressed withdrawal (4 assessed both). Only trials with an RA or axial SpA (axSpA) population were identified. An increased flare risk was demonstrated when b-/tsDMARD tapering was compared with continuation [RR 1.45 (95% CI 1.19, 1.77), I2 = 42.5%] and potentially increased for persistent flare [POR 1.56 (95% CI 0.97, 2.52), I2 = 0%]. Comparing TNF inhibitor (TNFi) withdrawal with continuation, a highly increased flare risk [RR 2.28 (95% CI 1.78, 2.93), I2 = 78%] and increased odds of persistent flare [POR 3.41 (95% CI 1.91, 6.09), I2 = 49%] were observed. No clear difference in flare risk between RA or axSpA was observed., Conclusion: A high risk for flare and persistent flare was demonstrated for TNFi withdrawal, whereas an increased risk for flare but not for persistent flare was observed for b-/tsDMARD tapering. Thus tapering seems to be the more favourable approach., Registration: PROSPERO (CRD42019136905)., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

As a result of the pandemic, many patients with an inflammatory rheumatic disease (IRD) have isolated themselves. The lack of disease management together with fear of infection could lead to changes in physical- and mental health. The aim of this study was to evaluate the social- and health behaviour in patients with an IRD compared with the behaviour of healthy individuals during the COVID-19 pandemic. The study was a questionnaire survey answered by patients with an IRD and healthy individuals (HI). The questionnaire contained seven sections with questions regarding COVID-19 and quality of life including SF-36, EQ-5D-5L, and visual analogue scale (VAS) pain, fatigue and global health. Of 1663 invited participants, 661 patients with IRD and 266 HI were included in the analyses. Patients with an IRD felt more isolated during the COVID-19 pandemic compared with HI (IRD: 9.5% (61/644), HI: 3.1% (8/259), p-value = 0.001). More HI (5.4%) had been infected with COVID-19 than patients with an IRD (1.7%). Among patients with an IRD those with worse self-reported disease activity outcomes (VAS pain, fatigue and global health, all p-value < 0.001), worse social functioning and emotional well-being were more isolated than individuals with low disease activity. Patients with an IRD feel more isolated during the COVID-19 pandemic compared to HI. Isolation seems to be most pronounced in patients with worse disease related patient-reported outcomes and lower quality of life., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Whiplash injury is common following road traffic crashes affecting millions worldwide, with up to 50% of the injured developing chronic symptoms and 15% having a reduced working capability due to ongoing disability. Many of these patients receive treatment in primary care settings based upon clinical and diagnostic imaging findings. Despite the identification of different types of injuries in the whiplash patients, clinically significant relationships between injuries and chronic symptoms remains to be fully established. This study investigated the feasibility of magnetic resonance imaging (MRI) techniques including quantitative diffusion weighted imaging and measurements of cerebrospinal fluid (CSF) flow as novel non-invasive biomarkers in a population of healthy volunteers and chronic whiplash patients recruited from a chiropractic clinic for the purpose of improving our understanding of whiplash injury., Methods: Twenty chronic whiplash patients and 18 healthy age- and gender matched control subjects were included [mean age ± SD (sex ratio; females/males), case group: 37.8 years ± 9.1 (1.22), control group: 35.1 years ± 9.2 (1.25)]. Data was collected from May 2019 to July 2020. Data from questionnaires pertaining to the car crash, acute and current symptoms were retrieved and findings from clinical examination and MRI including morphologic, diffusion weighted and phase-contrast images were recorded. The apparent diffusion coefficient and fractional anisotropy were calculated, and measurement and analysis of CSF flow was conducted. Statistical analyses included Fisher's exact test, Mann Whitney U test and analysis of variance between groups., Results: The studied population was described in detail using readily available clinical tools. No statistically significant differences were found between the groups on MRI., Conclusions: This study did not show that MRI-based measures of morphology, spinal cord and nerve root diffusion or cerebrospinal fluid flow are sensitive biomarkers to distinguish between chronic whiplash patients and healthy controls. The detailed description of the chronic whiplash patients using readily available clinical tools may be of great relevance to the clinician. In the context of feasibility, clinical practice-based advanced imaging studies with a technical setup similar to the presented can be expected to have a high likelihood of successful completion., (© 2022. The Author(s).)

Objectives: Patient-reported outcome measures (PROMs) are evaluated in randomized controlled trials (RCTs) in patients with systemic lupus erythematosus (SLE), but not widely used in clinical practice. However, interest in incorporating PROMs into the management of SLE is increasing as PROMs provide a unique insight into the patient's perception of lupus disease activity. The objective was to assess agreement in PROMs answered using a web app versus an outpatient touchscreen among patients with SLE., Methods: In a crossover RCT, SLE patients answered the following PROMs in a random order using the web app and the outpatient touchscreen: Systemic Lupus Erythematosus Activity Questionnaire (SLAQ) Global Health, SLAQ Symptom, SLAQ Total, SLAQ Worsening, Pain Visual Analog Scale (VAS), Fatigue VAS, Patient Global Health VAS, Health Assessment Questionnaire Disability Index (HAQ-DI), Patient Acceptable Symptom State (PASS), and an Anchoring Question. Equivalence between the two device types was demonstrated if the 95% confidence interval (95% CI) of the difference in PROM scores was within the prespecified equivalence margin. Agreement between the two device types was assessed using mixed linear models., Results: Thirty-four patients with SLE were included. Equivalence was demonstrated between the two device types for SLAQ Global Health with a difference of -0.21 (95% CI: -0.65 to 0.23). Moreover, equivalence was also found for HAQ-DI, Pain VAS, and Fatigue VAS whereas only comparability within the limits of the Minimal Clinically Important Difference (MCID) was demonstrated for VAS Patient Global Health. Statistical comparability was demonstrated for SLAQ Total, SLAQ Worsening, PASS, and Anchoring Question (no predefined MCID/equivalence margins available). However, a statistically significant difference between device types was observed for the SLAQ Symptom of -0.56 (95% CI: -1.10 to -0.01). The difference was, however, very small when considering the scale range of 0-24; thus, it was not judged to be of clinical relevance. Preference for the web app was very high (91.2%)., Conclusion: For the first time ever, equivalence and comparability between two electronic device types for various PROMs were demonstrated among patients with SLE. Implementation of the device is expected to improve the management of SLE.

Objectives: To estimate the incidence of COVID-19 hospitalization in patients with inflammatory rheumatic disease (IRD); in patients with RA treated with specific DMARDs; and the incidence of severe COVID-19 infection among hospitalized patients with RA., Methods: A nationwide cohort study from Denmark between 1 March and 12 August 2020. The adjusted incidence of COVID-19 hospitalization was estimated for patients with RA; spondyloarthritis including psoriatic arthritis; connective tissue disease; vasculitides; and non-IRD individuals. Further, the incidence of COVID-19 hospitalization was estimated for patients with RA treated and non-treated with TNF-inhibitors, HCQ or glucocorticoids, respectively. Lastly, the incidence of severe COVID-19 infection (intensive care, acute respiratory distress syndrome or death) among hospital-admitted patients was estimated for RA and non-IRD sp - individudals., Results: Patients with IRD (n = 58 052) had an increased partially adjusted incidence of hospitalization with COVID-19 compared with the 4.5 million people in the general population [hazard ratio (HR) 1.46, 95% CI: 1.15, 1.86] with strongest associations for patients with RA (n = 29 440, HR 1.72, 95% CI: 1.29, 2.30) and vasculitides (n = 4072, HR 1.82, 95% CI: 0.91, 3.64). There was no increased incidence of COVID-19 hospitalization associated with TNF-inhibitor, HCQ nor glucocorticoid use. COVID-19 admitted patients with RA had a HR of 1.43 (95% CI: 0.80, 2.53) for a severe outcome., Conclusion: Patients with IRD were more likely to be admitted with COVID-19 than the general population, and COVID-19 admitted patients with RA could be at higher risk of a severe outcome. Treatment with specific DMARDs did not affect the risk of hospitalization., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Introduction: The The BIOlogical Dose OPTimisation (BIODOPT) trial is a pragmatic, multicentre, randomised controlled, open-label, parallel-group, equivalence study designed to evaluate tapering of biological disease-modifying antirheumatic drugs (bDMARDs) in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA) in sustained clinical remission or low disease activity (LDA). Traditionally, these patients maintain standard dosage of bDMARD lifelong; however, recent studies indicate that a significant proportion of patients in sustained remission or LDA can taper their bDMARD and maintain stable disease activity. Thus, this trial aims to evaluate whether a disease activity-guided tapering strategy for bDMARDs will enable a significant dosage reduction while maintaining disease activity compared with usual care. From the individual patient's standpoint as well as from a societal perspective, it would be advantageous if bDMARDs could be reduced or even discontinued while maintaining disease activity., Methods and Analysis: A total of 180 patients with RA, PsA or axSpA treated with bDMARDs and in clinical remission/LDA during the past 12 months will be enrolled from four centres in Denmark. Patients will be randomised in a ratio of 2:1 to either disease activity-guided tapering of bDMARDs (intervention group) or continuation of bDMARDs as usual care (control group).The primary objective is the difference between the two groups in the proportion of patients who have reduced their inclusion dosage of bDMARDs to 50% or less while maintaining stable disease activity at 18 months follow-up., Ethics and Dissemination: The study is approved by the ethics committee of Northern Jutland, Denmark (N-20170073) and by the Danish Medicine Agency. Patient research partner KHH contributed to refinement of the protocol and approved the final manuscript. Results will be disseminated through publication in international peer-reviewed journals., Trial Registration Number: 2017-001970-41; Pre-results., Competing Interests: Competing interests: LU has received speaker honoraria from Abbvie, Eli Lilly and Novartis (not related to the submitted work). SK has received speaker honoraria from Novartis and Eli Lilly (not related to the submitted work). AS has received speaker honoraria from MSD and Eli Lilly (not related to the submitted work). LD has received speaker honoraria from UCB, MSD, Eli Lilly and Janssen Pharmaceutica (not related to the submitted work)., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Diffusion tensor imaging (DTI) has been applied in the lumbar and sacral nerves in vivo, but information about the reproducibility of this method is needed before DTI can be used reliably in clinical practice across centers., Purpose: In this multicenter study the reproducibility of DTI of the lumbosacral nerves in healthy volunteers was investigated., Study Type: Prospective control series., Subjects: Twenty healthy subjects., Field Strength/sequence: 3T MRI. 3D turbo spin echo, and 3.0 mm isotropic DTI scan., Assessment: The DTI scan was performed three times (twice in the same session, intrascan reproducibility, and once after an hour, interscan reproducibility). At site 2, 1 week later, the protocol was repeated (interweek reproducibility). Fiber tractography (FT) of the lumbar and sacral nerves (L3-S2) was performed to obtain values for fractional anisotropy, mean, axial, and radial diffusivity., Statistical Tests: Reproducibility was determined using the intraclass correlation coefficient (ICC), and power calculations were performed., Results: FT was successful and reproducible in all datasets. ICCs for all diffusion parameters were high for intrascan (ranging from 0.70-0.85), intermediate for interscan (ranging from 0.61-0.73), and interweek reliability (ranging from 0.58-0.62). There were small but significant differences between the interweek diffusivity values (P < 0.0005). Depending on the effect size, nerve location, and parameter of interest, power calculations showed that sample sizes between 10 and 232 subjects are needed for cross-sectional studies., Data Conclusion: We found that DTI and FT of the lumbosacral nerves have intermediate to high reproducibility within and between scans. Based on these results, 10-58 subjects are needed to find a 10% change in parameters in cross-sectional studies of the lumbar and sacral nerves. The small significant differences of the interweek comparison suggest that results from longitudinal studies need to be interpreted carefully, since small differences may also be caused by factors other than disease progression or therapeutic effects., Level of Evidence: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;48:951-963., (© 2018 The Authors Journal of Magnetic Resonance Imaging published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.)

Study Design: Cross-sectional autopsy study., Objective: Quantify histological changes in the lower cervical spine facet joints with regard to age and sex using systematic random sampling of entire joints., Summary of Background Data: Neck pain is a common debilitating musculoskeletal condition and one of the highest ranked causes of years lived with disability. The cause of neck pain is multifactorial and osteoarthritis is one potential cause. The cervical spine facet joints have been implicated in the etiology of chronic neck pain. Hence, a detailed description of their anatomy and age- and sex-related changes is needed., Methods: The lower four cervical spine segments (C4-C7 included) were obtained from 72 subjects during autopsy; 29 women (median age 53 years [22-77]) and 43 men (median age 38 years [20-78]). A total of 1132 articular facets were embedded in toto in hard plastic and sliced into 3-mm thick sections from where 10 μm thick histological sections were produced. Morphological variables were evaluated microscopically and histomorphometric variables were retrieved using random sampling methods. Data were analyzed with a linear regression model., Results: Significant associations were found between increasing age and in particular splitting, fissures, osteophytes, thickness of the calcified cartilage, and subchondral bone plate. The thickness of the calcified cartilage and subchondral bone plate increased with increasing age, whereas the hyaline cartilage thickness decreased. Males had more extensive degenerative changes in the cartilage., Conclusion: Using semiquantitative histological methods, degenerative findings were observed at all spinal levels involving the articular cartilage and the osseous structures of the cervical spine facet joints similar to those observed in larger weight-bearing joints. In particular, the thickening of the calcified cartilage and the subchondral bone identified the osteocartilaginous junction as an important area in osteoarthritis. These findings may be relevant for the pathogenesis of osteoarthritis., Level of Evidence: 3.

Mesenteric vasculitis is the most common abdominal manifestation of vasculitis and can present as acute abdominal pain. Mesenteric vasculitis is most frequent in systemic lupus erythematosus and polyarteritis nodosa in adulthood and immunoglobulin A-vasculitis in childhood. Involvement of other organs is also seen. The diagnosis can be challenging, but detailed clinical assessment in combination with diagnostic tests often identifies the underlying cause. Medical treatment is used, when the abdominal manifestation is considered reversible, while surgery is used in unstable patients or patients with non-reversible conditions.

Background: Bicyclists are vulnerable road users and are at risk of serious spinal injury if involved in traffic crashes. In Denmark approximately 25 bicyclists are killed each year and some 20.000 bicycle related casualties are registered in the National Patient Registry each year. In addition to these figures, a large number of casualties remain unregistered despite injury. Many of the casualties will consult chiropractors in primary practice with or without preceding evaluation in the established emergency care facilities. Therefore, chiropractors are expected to be able to proficiently evaluate these patients clinically and radiologically in order to ensure the best possible patient care., Case Presentation: This report involves a middle-aged female who consulted several physicians following a collision with a motor vehicle while riding a bike. Despite clinical symptoms and consequent examinations she suffered from inadequate diagnostic evaluation until a radiological examination was performed 18 days following the injurious crash identifying unstable cervical spine fractures., Conclusions: The presented case is an example of the serious spinal injuries bicyclists may suffer when involved in high-energy traffic crashes despite wearing a bicycle helmet. The case report highlights the need for relevant clinical (including radiological) decision strategies when dealing with trauma patients in chiropractic practice. This involves the direct access to radiological procedures with no unnecessary delay when indicated as in most trauma cases. Furthermore, clearly defined and easy accessible referral schemes from primary care settings to emergency departments must be available to the chiropractic physician. Chiropractors are clinically competent to examine and diagnose, including radiologically evaluate, patients who have been injured in traffic crashes. Hence, chiropractors may contribute to the diagnosis, management and rehabilitation of spinal injured patients following many types of crashes and accident, including bicycle crashes.

Purpose: While standard magnetic resonance imaging (MRI) sequences are increasingly employed in post-mortem (PM) examinations, more advanced techniques such as diffusion tensor imaging (DTI) remain unexplored in forensic sciences. Therefore, we studied the temporal stability and reproducibility of DTI and fiber tractography (FT) in non-fixed PM subjects. In addition, we investigated the lumbosacral nerves with PMDTI and compared their tissue characteristics to in vivo findings., Methods: MRI data were acquired on a 1.5T MRI scanner in seven PM subjects, consisting of six non-trauma deaths and one chronic trauma death, and in six living subjects. Inter-scan (within one session) and inter-session (between days) reproducibility of diffusion parameters, fractional anisotropy (FA), and mean diffusivity (MD), were evaluated for the lumbosacral nerves using Bland-Altman and Jones plots. Diffusion parameters in nerves L3-S2 were compared to living subjects using the non-parametric Mann-Whitney U test., Results: Reproducibility of diffusion values of inter-scan 95% limits of agreement ranged from -0.058 to 0.062 for FA, and (-0.037 to 0.052)×10(-3)mm(2)/s for MD. For the inter-session this was -0.0423 to 0.0423, and (-0.0442 to 0.0442)×10(-3)mm(2)/s for FA, and MD, respectively. Although PM subjects showed approximately four-fold lower diffusivity values compared to living subjects, FT results were comparable. The chronic trauma case showed disorganization and asymmetry of the nerves., Conclusion: We demonstrated that DTI was reproducible in characterizing nervous tissue properties and FT in reconstructing the architecture of lumbosacral nerves in PM subjects. We showed differences in diffusion values between PM and in vivo and showed the ability of PMDTI and FT to reconstruct nerve lesions in a chronic trauma case. We expect that PMDTI and FT may become valuable in identification and documentation of PM nerve trauma or pathologies in forensic sciences., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Spinal injury following inertial loading of the head and neck (whiplash) is a common sequel of low speed traffic crashes. A variety of non-musculoskeletal injuries have been described in association with injury to the spine following whiplash trauma, including traumatic brain injury, vestibular derangement, and cranial nerve injury, among others. Vascular injuries in the head and neck have, however, only rarely been described. We present the case of a middle-aged male who sustained an ultimately fatal injury that resulted from injury to the internal carotid artery (ICA) and intracerebral vascular structures following a hard braking maneuver, with no direct head- or neck contact with the vehicular interior. Based on this unusual mechanism of injury we reviewed hospital data from the United States nationwide inpatient database (NIS) to assess the frequency of similar injuries reportedly resulting from traffic crashes. The post-mortem examination revealed a left internal carotid artery dissection associated with subarachnoid hemorrhage (SAH). Based on the close temporal association, the absent prior history, and the plausibility of the injury mechanism, the injury was attributed to the braking maneuver. An analysis of NIS data demonstrated that the prevalence of subarachnoid hemorrhage is significantly higher when there is a traumatic etiology, and higher yet when the trauma is a traffic crash (odds ratio 3.3 and 4.3, respectively). The presented case, together with the hospital inpatient data analysis, indicate that although SAH in combination with ICA dissection is relatively rare, it is substantially more probable following a traffic crash. In a clinical or forensic setting the inference that magnitude of a trauma was low should not serve as a basis for either excluding a cervical artery dissection from a differential diagnosis, or for excluding the trauma as a cause of a diagnosed dissection. This case report illustrates a rare fatal outcome of inertial load to the head and neck induced by a sudden braking event in a commonly experienced non-collision traffic incident. The likely mechanism of injury resulted from interaction between the occupant and the 3-point seat belt. These findings indicate that ICA dissections are substantially more likely to be associated with SAH following head and neck trauma, regardless of the magnitude of the traumatic event or whether an impact was involved.

A fatal accident is reported in which a small single-engine light airplane crashed. The airplane carried two persons in the front seats, both of whom possessed valid pilot certificates. Both victims were subject to autopsy, including post-mortem computed tomography scanning (PMCT) prior to the autopsy. The autopsies showed massive destruction to the bodies of the two victims but did not identify any signs of acute or chronic medical conditions that could explain loss of control of the airplane. PMCT, histological examination, and forensic chemical analysis also failed to identify an explanation for the crash. A detailed review of an airplane identical to the crashed airplane was performed in collaboration with the Danish Accident Investigation Board and the Danish National Police, National Centre of Forensic Services. The injuries were described using the abbreviated injury scale, the injury severity score, 3-dimensional reconstructions of the PMCT, and an injury pattern analysis. We describe how, on basis of these data, we reached a conclusion about which of the two victims was the most likely to have been in control of the airplane at the time of accident. Furthermore, we argue that all victims of fatal airplane crashes should be subject to forensic autopsy, including PMCT and forensic chemical analysis. The continuous accumulation of knowledge about injury patterns from "simple" accidents is the foundation for the correct analysis of "difficult" accidents.

Animal anatomy has traditionally relied on detailed dissections to produce anatomical illustrations, but modern imaging modalities, such as MRI and CT, now represent an enormous resource that allows for fast non-invasive visualizations of animal anatomy in living animals. These modalities also allow for creation of three-dimensional representations that can be of considerable value in the dissemination of anatomical studies. In this methodological review, we present our experiences using MRI, CT and μCT to create advanced representation of animal anatomy, including bones, inner organs and blood vessels in a variety of animals, including fish, amphibians, reptiles, mammals, and spiders. The images have a similar quality to most traditional anatomical drawings and are presented together with interactive movies of the anatomical structures, where the object can be viewed from different angles. Given that clinical scanners found in the majority of larger hospitals are fully suitable for these purposes, we encourage biologists to take advantage of these imaging techniques in creation of three-dimensional graphical representations of internal structures.

Neck injuries resulting from motor vehicle collisions (MVC), often referred to as whiplash trauma and injury, often demonstrate little or no evidence of significant tissue damage. In rare instances, however, serious injury to the anterior neck organ injuries can result from such trauma. The present study describes esophageal injury associated with rear-impact collisions, based on a unique case report, review of the scientific literature and a query in the National Automotive Sampling System (NASS) database of the US National Highway Traffic Safety Administration. The Medline search and present case study totaled five cases of rear-impact collision-related serious esophageal injury (laceration or rupture). In the four published cases all patients survived, whereas in the presented case study, the patient died due to mediastinitis and sepsis. The NASS query revealed an additional three cases out of a total of 55,926 investigated crashes. All three cases were associated with fatalities. Although no anatomical or bioengineering studies have presented data on the behavior of the esophagus during rear-impact whiplash loading, sudden tensile and/or compressive forces is the likely explanation of injury, often in combination with a local fracture of a vertebral body. In these 8 cases significant esophageal injury carried a substantial (50%) risk of mortality. Clinicians should be aware of the potential for significant complications in the whiplash trauma-exposed patient who complains of chest pain, mid-thoracic pain, discomfort in the neck and throat, respiratory distress, or hoarseness. For those forensic specialists involved in whiplash cases these study results highlight the need to consider esophageal injuries as a rare but potential consequence of whiplash trauma., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Injuries to the upper cervical spine (UCS) are common in traumatic deaths and postmortem computed tomography (PMCT) may contribute to the forensic investigation. This study presents PMCT in comparison with autopsy in the examination of UCS injury. Thirteen consecutive cases with UCS fracture and ⁄ or cranio-cervical dislocation were examined with PMCT and autopsy, and the findings were correlated. Neither of the techniques identified all UCS injuries. Fractures of atlas and axis were best visualized with PMCT whereas cranio-cervical dislocation was better identified during autopsy. Serious injuries were present after both high- and low-energy trauma. Medico-legal autopsy in combination with PMCT produced a thorough evaluation of UCS injuries. By combining these procedures detailed investigations, including accident reconstruction and injury pattern analysis, can be performed. This study supports the routine application of PMCT, as a supplement to the medico-legal autopsy of deaths with UCS injuries.

Introduction: In some road traffic crashes with fatal outcome, the police investigations lead to charges against and prosecution of a person. The police can request a medico-legal autopsy as well as a toxicological examination, but the extent to which this is done, and the role here of in the legal setting is unknown., Material and Methods: Information concerning traffic crashes with fatal outcome in the period 2000-2004 in Aarhus Police District was retrieved and compared. The information included comprised crash specific and legal information, as well as medical data concerning autopsy, examination for alcohol, drugs and/or medicine., Results: In all, 81 traffic crashes had a fatal outcome for 92 persons, of whom 17 (18%) were autopsied, 55 (60%) were tested for alcohol, and five (5%) were examined for drugs/medicine. Twenty-six were charged with negligent homicide, of which 18 were convicted. Autopsy was performed in four of these cases, 19 were tested for alcohol and one was tested for drugs/medicine., Conclusion: This study shows that the police requests few medico-legal autopsies following road traffic fatalities, and that testing for alcohol as well as drugs/medicine is not conducted routinely. As a consequence, important information may not come to the knowledge of the police in cases of negligent homicide. We recommend that postmortem examination be conducted routinely in traffic-related homicide cases to secure the best possible conditions for a legal evaluation.

Ankylosing spondylitis (AS) is a chronic rheumatic disease that causes spinal rigidity with an increased risk of spinal fractures. We present a case report where a middle-aged man, in apparent good health, died following a fall from his bike. Postmortem computed tomography (CT) showed several fractures in the cervical and thoracic spine, with displacement into the spinal canal as well as spinal changes consistent with AS. The cause of death was determined to be upper spinal cord injury caused by cervical spinal fractures that were facilitated by spinal rigidity from AS. Further investigation into the medical records revealed that the decedent had previously been treated for AS. This case report illustrates the importance of obtaining a detailed medical history when investigating deaths, including nonfatal conditions, such as AS. Furthermore, it shows the value of CT in the evaluation of the mechanism and manner of death.

Background: In biomedical sciences, ex vivo angiography is a practical mean to elucidate vascular structures three-dimensionally with simultaneous estimation of intravascular volume. The objectives of this study were to develop a magnetic resonance (MR) method for ex vivo angiography and to compare the findings with computed tomography (CT). To demonstrate the usefulness of this method, examples are provided from four different tissues and species: the human placenta, a rice field eel, a porcine heart and a turtle., Results: The optimal solution for ex vivo MR angiography (MRA) was a compound containing gelatine (0.05 g/mL), the CT contrast agent barium sulphate (0.43 mol/L) and the MR contrast agent gadoteric acid (2.5 mmol/L). It was possible to perform angiography on all specimens. We found that ex vivo MRA could only be performed on fresh tissue because formalin fixation makes the blood vessels permeable to the MR contrast agent., Conclusions: Ex vivo MRA provides high-resolution images of fresh tissue and delineates fine structures that we were unable to visualise by CT. We found that MRA provided detailed information similar to or better than conventional CTA in its ability to visualize vessel configuration while avoiding interfering signals from adjacent bones. Interestingly, we found that vascular tissue becomes leaky when formalin-fixed, leading to increased permeability and extravascular leakage of MR contrast agent.

Injuries to the lower cervical spine facet joints may be identified in people killed in road traffic crashes. However, many of these injuries are not identified on diagnostic imaging procedures despite histological evidence of injury. This case report illustrates possible non-lethal pathological conditions in the facet joints following fatal road traffic trauma. The cervical spine segments C4 to C7 were removed en bloc and examined with magnetic resonance imaging, computed tomography and conventional radiology. The specimen was fixated in alcohol, embedded in methylmethacrylate, and divided into 3 mm thick parasaggital slices from where 10 microm thick sections were produced and evaluated with light microscopy. Injuries identified on microscopy included haemarthrosis, capsular avulsion, synovial fold contusions and subchondral fractures. None of the injuries were detected on diagnostic imaging or at routine autopsy. Discrete injuries to the cervical spine facet joints were identified using supplemental histological procedures in this case report. Post-mortem diagnostic imaging did not reveal these injuries and future studies should investigate the nature, prevalence and clinical relevance of such lesions.

Non-lethal injuries to the cervical spine facet joints have previously been described in decedents from motor vehicle crashes and in clinical settings these joints have been identified as potential culprits in chronic neck pain syndromes. The aim of this study was to conduct a detailed examination of the lower cervical spine facet joints in a forensic cohort of motor vehicle crash victims and controls using comparable data from medicolegal autopsy, stereomicroscopy and histological evaluations. Injuries to the cervical spine facet joints were common in the trauma cases and included facet fractures, haemarthrosis, and disruption and bleeding in the synovial folds. The injuries could not be reliably verified on stereomicroscopic evaluation, and routine autopsy procedures did not reveal any of the injuries to the facet joints. Despite the presence of these pathoanatomical lesions in road traffic crash fatalities their prevalence and potential clinical implications in survivors from motor vehicle crashes is unknown.

Computerized Tomography (CT) is used by some forensic pathology departments as a supplement to the forensic autopsy. Departments with a limited number of autopsies may find it relatively expensive to acquire and operate a CT-scanner. Furthermore, it requires a great deal of training and experience to interpret the radiological data. We are currently evaluating CT in order to decide whether the benefits match the efforts. In selected death-investigations the Department of Radiology at Aarhus University Hospital performs CT of the body on behalf of the Institute of Forensic Medicine at Aarhus University and a skilled radiologist interprets the data. We present our radiological findings in the 20 cases where we have used CT and compare them to the autopsy findings. The cases include fatalities from beatings, stabbings, gunshots, fires and traffic accidents. CT is an excellent tool for documenting and illustrating certain lesions, such as gunshot wounds and bone fractures, where we can obtain information that possibly would have been missed at the autopsy. We believe, however, that further research is required before we can recommend CT as a part of a standard forensic autopsy. The cooperation between forensic and radiological departments is a good approach for smaller forensic departments that insures a skilled interpretation without having to divert a lot of resources to equipment and training.

Whiplash injuries have increased in numbers during recent decades. The highest incidence rates of whiplash injury are found in low speed motor vehicle crashes during which many vehicles do not sustain significant property damage despite the fact that occupants may suffer personal injury. This article investigates the relationship between car crash velocity changes and residual vehicular damage in low speed crashes and personal injury thresholds. It can be concluded that a personal injury threshold in relation to velocity change and property damage in low speed motor vehicle crashes cannot be established based on scientific evidence.

A naked man died under peculiar circumstances and the postmortem examination revealed unexpected lesions in the cervical spine. Investigations of the cervical spine (computed tomography, magnetic resonance imaging, and histological examination) showed that a piece of bone was torn of the anterior part of vertebra C6 and that there was fresh bleeding in the surrounding tissue. The cause of death remained unclear but was most likely cardiac arrhythmia initiated by beta-2 agonist inhalation due to an acute asthmatic attack. Data from biomechanical investigation using finite element analysis supported the conclusion that the cervical spine injury was secondary to impact during falling as a consequence of the cardiac arrhythmia.

Study Design: A systematic critical literature review., Objectives: To determine whether occult pathoanatomical lesions in the cervical spine of road traffic fatalities exist and if they can be identified using optimal autopsy techniques., Summary of Background Data: Previous investigations have examined pathoanatomical conditions of the cervical spine of road traffic fatalities. However, different methods of investigation have been used, and results of studies are conflicting. Hence, potential pathoanatomical conditions in fatalities and survivors remain a controversial issue., Methods: Articles were retrieved searching the MEDLINE, Mantis, and Cochrane libraries. Studies examining the cervical spine of road traffic fatalities at autopsy were included and evaluated according to a set of quality criteria. For in-depth review, only studies using surface cryoplaning microtomy autopsy technique and a control group were included., Results: Twenty-seven articles of which three fulfilled the quality criteria were reviewed. In these studies, subtle pathoanatomical lesions were found in the cervical intervertebral discs, cartilaginous endplates, and the articular surfaces and capsules of the zygapophysial joints. The lesions were found exclusively in the traumatized patients and in none of the patients in the control group., Conclusions: Occult pathoanatomical lesions in the cervical intervertebral disc and zygapophysial joints after fatal road traffic trauma may exist. Present imaging methods, especially conventional radiography, do not visualize these subtle lesions; hence, underreporting of pathoanatomical lesions during standard autopsy is probably common. These findings may have clinical relevance in the management of road traffic trauma survivors with potentially similar pathoanatomy.

A characteristic feature of chordomas is the content of a great amount of mucinous material. A sacrococcygeal chordoma surgically removed from a 76-year-old man was histochemically investigated in order to obtain some information about the composition of the mucopolysaccharides. From the results of the staining reactions, we concluded that they are of the acid category and probably a mixture of weakly sulphated and carboxylated glycoproteins.