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In concrete structures, material performance is typically determined at the level of the concrete mix (the microscale) and the overall shape and dimensions of a building element (the macroscale). However, recent developments in the field of 3D Concrete Printing (3DCP) are demonstrating that the design of concrete now also can take place at a previously impossible intermediate scale involving the shaping and placement of the material at the level of the printing nozzle (the mesoscale). By focusing directly on the design of print paths, advanced surface effects and internal porous material distributions can be achieved that significantly affect the aesthetic experience and structural performance of 3DCP structures. This ability to design the distribution of concrete according to local architectural, structural, and functional design criteria is an especially interesting application of 3DCP that could be exploited to customise material performance while at the same time optimising material use and reducing the self-weight of building elements. This paper specifically examines how four different three-dimensional print patterns produce distinct material structures at the mesoscale (mesostructures) and presents an experimental procedure for evaluating their load-bearing capacity.

Functionally graded materials (FGMs) describe composite materials with a gradual change in properties along one or several axes. A major advantage with this approach is the avoidance of discontinuities between different layers of material. 3D Printing offers the possibility to control the material composition and spatial placement along the printing process to create structures with graded properties. However, there are very few examples of the application of this approach to 3D concrete printing (3DCP). This paper presents a review of the current approaches of and methods to grade the material properties of a 3DCP structure, as well as a review of similar methods used in other 3D printing processes. Finally, the potential applicability of these principles into concrete are presented and discussed.

Aims: Personalised medicine in chronic complex diseases such as rheumatoid arthritis (RA) is within reach but requires international multi-stakeholder collaboration. We exemplify how national implementations of the General Data Protection Regulation (GDPR) have introduced administrative delays and created disincentives for data sharing and collaborative research., Methods: Our Danish/Swedish/Norwegian research collaboration (the 3-year NordForsk-funded "NORA" project) aims to develop a personalised medicine approach for the management of RA, built on the exploitation of unique existing data sources: longitudinal data from clinical rheumatology registries, research cohorts, nationwide health care registries, and biobank material from >20 sample collections. Data and results are shared and accessed remotely by collaborators at secure servers. New biomarker assays and patient-centric implementations of the results are to be explored, validated, and disseminated to patients and health care via the development of digital tools., Results: Following the advice of legal experts at the involved academic or public institutions and private companies, GDPR compliance resulted in >20 legal documents to govern the collaboration (consortium-, joint controller-, research collaboration-, data sharing-, and a series of unique two-way data processing-, and material transfer agreements). Lack of agreed-upon templates, policies, procedures, and a shortage of legal resources have caused considerable delays. Thus, our research consortium has spent more time ensuring GDPR compliance than on actual research activities., Conclusions: The current interpretation and implementation of the legal premises (rather than the GDPR per se) for research collaborations caused unnecessary barriers and delays. Our experiences call for Nordic trust-based code-of-conduct-like framework agreements, and for harmonisation of procedures and templates, lest the Nordic advantage in research be lost., Competing Interests: Declaration of conflicting interestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Bente Glintborg: research grants (paid to institution) from Pfizer, Sandoz, AbbVie, BMS. Chairs the steering committee of the Danish Rheumatology Quality Registry (DANBIO, DRQ), which receives public funding from the hospital owners and funding from pharmaceutical companies.Hilde Berner Hammer: honoraria and/or research grants from AbbVie, Lilly, UCB, Pizer and Novartis.Saedis Saevarsdottir: part-time employee of deCODE genetics.Johan Rönnelid: advisory board member for Thermo Fisher Scientific and Werfen/Inova.Isabel Gehring: employee of Thermo Fisher Scientific.Merete Lund Hetland: all the following has been paid to institutions (i.e. no personal income): study grants or contracts with AbbVie, Biogen, BMS, Celltrion, Eli Lilly; Janssen Biologics B.V., MSD, Pfizer, Roche, Samsung Biopies, Sandoz, Novartis, UCB. Lectures or presentations: Pfizer, Medac, Sandoz. AdBoard: AbbVie. MLH co-chairs EuroSpA, which generates real-world evidence of treatment of psoriatic arthritis and axial spondylorthritis based on secondary data and is partly funded by Novartis and UCB.Tue Kragstrup: speaking fees from Pfizer, Bristol-Myers Squibb, Eli Lilly, Novartis, UCB, and AbbVie. Consultancy fees from Bristol-Myers Squibb, UCB, Gilead, and Eli Lilly. Research grants from Gilead. Co-founder and clinical developer in Aptol Pharma.Ellen-Margrethe Hauge: fees for speaking and/or consulting from Novartis, AbbVie, Sanofi, Sobi; research funding to Aarhus University Hospital from Novo Nordic Foundation, Danish Rheumatism Association, Danish Regions Medicine Grants, Roche, Novartis, AbbVie; travel expenses from Pfizer, Sobi, AbbVie. Has been principal investigator of studies by SynACT Pharma and involved as site principal investigator in trials by AbbVie, Novartis, Novo, Sanofi. None of the aforementioned undertakings relate to this manuscript.Johan Askling: Karolinska Institutet has entered into agreements with the following companies, with Johan Askling as principal investigator: Abbvie, BMS, Eli Lilly, Galapagos, Janssen, Pfizer, Roche, Samsung Bioepis and Sanofi.The remaining authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Patients with idiopathic inflammatory myopathies (IIM) have an increased risk of cancer, but their cancer-related disease burden remains unclear., Objectives: To explore how cancer might impact the mortality of patients with IIM and examine the associated prognostic factors for cancer and death., Methods: We identified patients with IIM diagnosed between 1998 and 2020 and ascertained their cancer and death records via linkage to the Swedish healthcare and population registers. Transition hazards from IIM diagnosis to cancer and death were estimated in multistate models using flexible parametric methods. We then predicted the probability of having cancer or death, and the duration of staying alive at a given time from IIM and cancer diagnoses from a crude model. We also explored prognostic factors for progression to cancer and death in a multivariable model., Results: Of 1826 IIM patients, 310 (17%) were diagnosed with cancer before and 306 (17%) after IIM diagnosis. In patients diagnosed with cancer after IIM, the 5-year probability of death from cancer and from other causes was 31% and 18%, respectively, compared to 7% and 15% in patients without cancer after IIM. We reported several factors associated with risk of progression to cancer and death. Specifically, patients with first cancer after IIM who were older at IIM diagnosis, had cancer history, dermatomyositis and a cancer diagnosis within 1 year following IIM faced a greater cancer-specific mortality., Conclusion: We observed a substantial increase in mortality from cancer, compared to before, rather than other causes after a cancer diagnosis following IIM, suggesting an unmet medical need for effective cancer management in IIM patients. This finding, along with the identified prognostic factors, provides useful insight into future research directions for improving cancer management in IIM patients., (© 2024 The Author(s). Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.)

Objective: The aim of this study was to investigate whether a shared genetic susceptibility exists between individuals with rheumatoid arthritis (RA) and individuals with myocardial infarction (MI)-including major MI risk factors-and to quantify the degree of any such overlap., Methods: Genome-wide association study (GWAS) data for individuals with RA were constructed from a sample of 26,637 Swedish patients with RA and controls without RA. For patients with MI, GWAS data were obtained from a previously published meta-analysis. Genome-wide genetic correlation was estimated via linkage disequilibrium score regression. LAVA was employed to estimate local genetic correlations in ~2,500 nonoverlapping loci, including the major histocompatibility complex. The controls without RA were used for reference panel data. We also assessed stratified estimates of both genome-wide and local genetic correlation based on subsamples of individuals with seropositive RA and those with seronegative RA. Furthermore, genome-wide genetic correlation was estimated between RA and selected cardiovascular risk factors to elucidate pleiotropic relationships., Results: Following quality control, our GWAS of patients with RA consisted of 25,826 individuas. Genome-wide genetic correlation between patients with RA and MI was estimated to 0.13 (95% confidence interval -0.03 to 0.29). Six regions exhibited significant local genetic correlation, though none harbored any known risk single-nucleotide polymorphisms for either of the two traits. Estimates were similar in both individuals with seropositive RA and those with seronegative RA. No statistically significant genetic correlations were observed between RA risk factors and any of the MI risk factors., Conclusion: Our findings indicate that genetic overlap between patients with RA and MI is minor. Furthermore, genetic overlap between RA and MI risk factors seem unlikely to provide a major contribution to the increased risk of MI observed in patients with RA., (© 2024 The Author(s). Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Objectives: To investigate the influence of genetic factors on persistence with treatment of early RA with MTX monotherapy., Methods: We conducted a genome-wide association study (GWAS) in a sample of 3902 Swedish early-RA patients initiating MTX in DMARD monotherapy as their first-ever DMARD. The outcome, short- and long-term MTX treatment persistence, was defined as remaining on MTX at 1 and at 3 years, respectively, with no additional DMARDs added. As genetic predictors, we investigated individual SNPs, and then calculated a polygenic risk score (PRS) based on SNPs associated with RA risk. The SNP-based heritability of persistence was estimated overall and by RA serostatus., Results: No individual SNP reached genome-wide significance (P < 5 × 10-8), either for persistence at 1 year or at 3 years. The RA PRS was not significantly associated with MTX treatment persistence at 1 year [relative risk (RR) = 0.98 (0.96-1.01)] or at 3 years [RR = 0.96 (0.93-1.00)]. The heritability of MTX treatment persistence was estimated to be 0.45 (0.15-0.75) at 1 year and 0.14 (0-0.40) at 3 years. The results in seropositive RA were comparable with those in the analysis of RA overall, while heritability estimates and PRS RRs were attenuated towards the null in seronegative RA., Conclusion: Despite being the largest GWAS on an MTX treatment outcome to date, no genome-wide significant associations were detected. The modest heritability observed, coupled with the broad spread of suggestively associated loci, indicate that genetic influence is of polygenic nature. Nevertheless, MTX monotherapy persistence was lower in patients with a greater genetic disposition, per the PRS, towards RA., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Objectives: To investigate how individual rheumatoid arthritis (RA) autoantibodies associate with individual signs and symptoms at the time of RA diagnosis., Methods: IgA, IgG, IgM rheumatoid factor (RF), antibodies against cyclic citrullinated peptide version 2 (anti-CCP2) and 16 individual antibodies against citrullinated protein (ACPA) reactivities were analysed centrally in baseline sera from 1600 patients with RA classified according to the 1987 American College of Rheumatology (ACR) criteria. These results were related to C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), number of swollen and tender joints (SJC and TJC), 28-joint disease activity scores (DAS28 and DAS28CRP), global disease activity evaluated by the patients and Health Assessment Questionnaire, all obtained at baseline., Results: Individually, all autoantibodies except immunoglobulin G (IgG) RF associated with low SJC and TJC and with high ESR. In IgM RF-negative patients, ACPA associated strictly with low number of swollen and tender joints. This association persisted in multiple regression and stratified analyses where IgM and IgA RF instead associated with inflammation expressed as ESR. Among subjects without any ACPA peptide reactivity, there was no association between RF isotypes and ESR. The effect of RF on ESR increased with the number of ACPA reactivities, especially for IgM RF. In patients fulfilling the 1987 ACR criteria without taking RF into account, associations between IgM RF and high ESR, as well as between ACPA and low joint counts, remained., Conclusion: Whereas ACPA associate with low counts of affected joints in early RA, RF associates with elevated measures of systemic inflammation in an ACPA-dependent manner. This latter finding corroborates in vitro models of ACPA and RF in immune complex-induced inflammation. These phenotypic associations are independent of classification criteria., Competing Interests: Competing interests: EP and LM-A are employees at Thermo Fisher Scientific. JA has had or have research agreements with AbbVie, BMS, Eli Lilly, Galapagos, MSD, Pfizer, Roche, Samsung Bioepis and Sanofi, mainly for the national safety monitoring of rheumatology immunomodulators in Sweden (ARTIS). JR has been a member of the Scientific Advisory Board for Thermo Fisher Scientific and for Inova/Werfen and has received consulting fees, speaking fees and/ or honoraria by Thermo Fisher Scientific. RH has received consulting fees from Regor, Lipum AB and Cyxone AB and is the founder of Vacara AB. LK has been a co-ordinator of several IMI-funded projects which included collaborations with Janssen, Pfizer, Sanofi, UCB, GSK and Eli-Lilly. This work has been presented as a poster in a preliminary form at EULAR (June 2019) and to the European Workshop for Rheumatology Research (March 2023)., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: This study aims to examine whether comorbidities affect the likelihood of reaching primary remission on methotrexate monotherapy as the first disease-modifying antirheumatic drug (DMARD) in early rheumatoid arthritis (RA)., Methods: We used nationwide Swedish clinical and quality registers to collect RA disease activity measures and comorbidity data for patients diagnosed with RA 2007-2020 (n=11 001). The primary outcome was failure to reach 28-joint Disease Activity Score (DAS28) remission at 3 months. Secondary outcomes included Boolean, Simplified Disease Activity Index/Clinical Disease Activity Index remission, European Alliance of Associations for Rheumatology response and no swollen joint count at 3 and 6 months. For each comorbidity, and for combinations thereof, we calculated adjusted relative risks (RRs) of failure to reach remission, using modified Poisson regression., Results: In total, 53% (n=4019/7643) failed to reach DAS28 remission after 3 months of methotrexate monotherapy, ranging from 66% (n=25/38) among patients with chronic kidney disease to 48% (n=154/319) in patients with previous cancer. The risk of not reaching DAS28 remission at 3 months (RR adjusted for sex and age) was increased among patients with endocrine (RR 1.08, 95% CI 1.01 to 1.15), gastrointestinal (RR 1.16, 95% CI 1.03 to 1.30), infectious (RR 1.21, 95% CI 1.06 to 1.38), psychiatric (RR 1.24, 95% CI 1.15 to 1.35) and respiratory comorbidities (RR 1.16, 95% CI 1.01 to 1.32). Having three or more comorbidity categories was associated with a 27% higher risk of DAS28 remission failure at 3 months. A similar pattern was observed for the secondary outcomes., Conclusions: Comorbidities decrease the chance of reaching remission on methotrexate as DMARD monotherapy in patients with early RA and are important to consider when assessing treatment outcomes., Competing Interests: Competing interests: JA has received grants from Abbvie, AstraZeneca, BMS, Eli Lily, MSD, Pfizer, Roche, Samsung Bioepis, Sanofi and UCB; these entities have entered into agreements with Karolinska Institutet with JA as principal investigator mainly in the context of safety monitoring of biologics via ARTIS/Swedish Biologics Register. SS is a part-time employee of deCODE genetics, unrelated to this work. The other authors have declared no conflicts of interest., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Background: The two main phenotypes of multiple sclerosis (MS), primary progressive (PPMS) and relapsing Onset (ROMS), show clinical and demographic differences suggesting possible differential risk mechanisms. Understanding the heritable features of these phenotypes could provide aetiological insight., Objectives: To evaluate the magnitude of familial components in PPMS and ROMS and to estimate the heritability of disease phenotypes., Methods: We used data from 25,186 MS patients of Nordic ancestry from the Swedish MS Registry between 1987 and 2019 with known disease phenotype (1593 PPMS and 16,718 ROMS) and 251,881 matched population-based controls and 3,364,646 relatives of cases and controls. Heritability was calculated using threshold-liability models. For familial odds ratios (ORs), logistic regression with robust sandwich estimator was utilized., Results: The OR of MS diagnosis in those with a first-degree family member with ROMS was 7.00 and 8.06 in those with PPMS. The corresponding ORs for having a second-degree family member with ROMS was 2.16 and 2.18 in PPMS. The additive genetic effect in ROMS was 0.54 and 0.22 in PPMS., Conclusion: Risk of MS increases by several folds in those with a relative with MS. The likelihood of developing either disease phenotype appears independent of genetic predisposition.

Objective: Precision medicine in rheumatoid arthritis (RA) requires a good understanding of treatment outcomes and often collaborative efforts that call for data harmonisation. We aimed to describe how harmonisation across study cohorts can be achieved and investigate how the observed proportions reaching remission vary across remission criteria, study types, disease-modifying antirheumatic drugs (DMARDs) and countries, and how they relate to other treatment outcomes., Methods: We used data from eight existing large-scale, clinical RA registers and a pragmatic trial from Sweden, Denmark and Norway. In these, we defined three types of treatment cohorts; methotrexate monotherapy (as first DMARD), tumour necrosis factor inhibitors (TNFi) (as first biological DMARD) and rituximab. We developed a harmonised study protocol defining time points during 36 months of follow-up, collected clinical visit data on treatment response, retention, persistence and six alternative definitions of remission, and investigated how these outcomes differed within and between cohorts, by treatment., Results: Cohort sizes ranged from ~50 to 22 000 patients with RA. The proportions reaching each outcome varied across outcome metric, but with small to modest variations within and between cohorts, countries and treatment. Retention and persistence rates were high (>50% at 1 year), yet <33% of patients starting methotrexate or TNFi, and only 10% starting rituximab, remained on drug without other DMARDs added and achieved American Congress of Rheumatology/European Alliance of Associations for Rheumatology or Simplified Disease Activity Index remission at 1 year., Conclusion: Harmonisation of data from different RA data sources can be achieved without compromising internal validity or generalisability. The low proportions reaching remission, point to an unmet need for treatment optimisation in RA., Competing Interests: Competing interests: SS is a part-time employee at deCODE genetics. E-MH has received institutional grants or contracts from Novo Nordic Foundation, Danish Rheumatism Association, Danish Regions Medicine Grants, Rocke, Novartis or Abbvie, payment or honoraria for lecture, presentations, speakers bureaus, manuscript writing or educational events from Sobi, support from attending meetings and/or travel from Pfizer, Sobi and Abbvie. participated on data safety monitoring board or advisory board for Novartis, Abbvie and Sanofi and is principal investigator in trials by SynACT Pharma, site principal investigator in trials by AbbVie, Novartis, Novo and Sanofi. HBH has received honoraria for lectures from AbbVie, Novartis, Lilly and UCB, and participated on advisory board for AbbVie, UCB and Novarties. Karolinska Institutet has entered into agreements with the following companies, with JA as PI: Abbvie, BMS, Eli Lilly, Galapagos, Janssen, Pfizer, Roche, Samsung Bioepis and Sanofi. BG has received research grant from Pfizer, AbbVie, BMS and Sandoz. The remaining authors have nothing to declare., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To examine if idiopathic inflammatory myopathies (IIMs) share familial susceptibility with cancer, we estimated the familial co-aggregation of these diseases., Methods: This Swedish population-based family study with data from national registers included 8,460 first-degree relatives of patients with IIM and 41,127 relatives of matched individuals without IIM. We modeled the adjusted odds ratios (ORs) of familial co-aggregation of IIM and cancer using conditional logistic regressions and adjusted for sex and birth year of index individuals and their first-degree relatives. We examined the associations for cancer overall and stratified by several factors of interest. We also performed exploratory analyses for specific cancer types., Results: We observed no statistically significant familial associations between IIM and cancer overall. However, there was a familial association in male relative pairs of patients with dermatomyositis (adjusted OR for familial association 1.39 [95% confidence interval (95% CI) 1.15-1.68]). The association remained statistically significant after controlling for multiple testing. Moreover, this finding was consistent between kinships. Familial co-aggregation of IIM and cancer diagnosed before 50 years of age was only observed in offspring. In exploratory analyses, only the familial associations for myeloid malignancies (adjusted OR 2.27 [95% CI 1.43-3.60]) and liver cancer (adjusted OR 2.01 [95% CI 1.21-3.33]) in male relative pairs remained significant after controlling for multiple testing., Conclusion: We found little evidence of shared familial susceptibility as a major pathologic mechanism contributing to the co-occurrence of IIM and cancer overall. There could be subsets of patients and cancer types for which familial factors including genetics and shared environments are of more importance, but these findings need replication., (© 2023 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Objectives: To assess the association between venous thromboembolic (VTE) events and autoantibodies, following patients from RA diagnosis, measuring occurrence, levels and collective load of different autoantibodies against post-translational protein modifications, in particular recognizing citrullination (e.g. citrullinated fibrinogen) and RF by isotype., Methods: A cohort of 2814 patients with newly diagnosed RA were followed for incident VTE through register linkages. Sera from RA diagnosis were centrally analysed for antibodies to second generation cyclic citrullinated peptides (anti-CCP2), 20 anti-citrullinated protein antibody (ACPA) fine-specificities, antibodies to additional protein modifications (carbamylation and acetylation) and RF by isotype. Association between baseline serology status and future VTE was analysed using Cox regression adjusted for age, sex and calendar period of RA diagnosis, overall and stratified by anti-CCP2 and RF positivity., Results: During a median 16 years of follow-up, 213 first-ever VTE events were registered (5.0/1000 person-years). IgG anti-CCP2 (present in 65% of cohort) associated with VTE (hazard ratio [HR] = 1.33, 95% CI: 1.00, 1.78), in a dose-response manner. The risk of VTE increased with number of ACPA fine-specificities. IgM RF, but no other RF isotypes, associated with VTE (HR = 1.38, 95% CI: 1.04, 1.82). The associations were independent from smoking and HLA-DRB1 shared epitope alleles. None of the carbamylated or acetylated antibody reactivities associated with VTE., Conclusion: Anti-CCP2, load of ACPA fine-specificities and IgM RF at RA diagnosis are associated with an increased risk of future VTE in RA. Antibodies to citrullinated fibrinogen did not differ substantially from other ACPA fine-specificities. Autoreactivity to other post-translational modifications was not associated with VTE risk., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Background: Methotrexate (MTX) is the first line treatment for rheumatoid arthritis (RA), but failure of satisfying treatment response occurs in a significant proportion of patients. Here we present a longitudinal multi-omics study aimed at detecting molecular and cellular processes in peripheral blood associated with a successful methotrexate treatment of rheumatoid arthritis., Methods: Eighty newly diagnosed patients with RA underwent clinical assessment and donated blood before initiation of MTX, and 3 months into treatment. Flow cytometry was used to describe cell types and presence of activation markers in peripheral blood, the expression of 51 proteins was measured in serum or plasma, and RNA sequencing was performed in peripheral blood mononuclear cells (PBMC). Response to treatment after 3 months was determined using the EULAR response criteria. We assessed the changes in biological phenotypes during treatment, and whether these changes differed between responders and non-responders with regression analysis. By using measurements from baseline, we also tried to find biomarkers of future MTX response or, alternatively, to predict MTX response., Results: Among the MTX responders, (Good or Moderate according to EULAR treatment response classification, n = 60, 75%), we observed changes in 29 partly overlapping cell types proportions, levels of 13 proteins and expression of 38 genes during treatment. These changes were in most cases suppressions that were stronger among responders compared to non-responders. Within responders to treatment, we observed a suppression of FOXP3 gene expression, reduction of immunoglobulin gene expression and suppression of genes involved in cell proliferation. The proportion of many HLA-DR expressing T-cell populations were suppressed in all patients irrespective of clinical response, and the proportion of many IL21R+ T-cells were reduced exclusively in non-responders. Using only the baseline measurements we could not detect any biomarkers or prediction models that could predict response to MTX., Conclusion: We conclude that a deep molecular and cellular phenotyping of peripheral blood cells in RA patients treated with methotrexate can reveal previously not recognized differences between responders and non-responders during 3 months of treatment with MTX. This may contribute to the understanding of MTX mode of action and explain non-responsiveness to MTX therapy., Competing Interests: SJ, MMa, and DZ were employed by Pfizer. LF was employed by Novo Nordisk A/S during data generation for this study and currently is employed by Nucleus Genomics. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Brynedal, Yoosuf, Ulfarsdottir, Ziemek, Maciejewski, Folkersen, Westerlind, Müller, Sahlström, Jelinsky, Hensvold, Padyukov, Pomiano, Catrina, Klareskog and Berg.)

Objectives: To conduct the first-ever nationwide, population-based cohort study investigating survival patterns of all patients with incident SSc in Sweden compared with matched individuals from the Swedish general population., Methods: We used the National Patient Register to identify patients with incident SSc diagnosed between 2004 and 2015 and the Total Population Register to identify comparators (1:5), matched on sex, birth year and residential area. We followed them until death, emigration or the end of 2016. Follow-up of the general population comparators started the same date as their matched patients were included. We estimated all-cause survival using the Kaplan-Meier method, crude mortality rates and hazard ratios (HRs) using flexible parametric models., Results: We identified 1139 incident patients with SSc and 5613 matched comparators. The median follow-up was 5.0 years in patients with SSc and 6.0 years for their comparators. During follow-up, 268 deaths occurred in patients with SSc and 554 in their comparators. The 5-year survival was 79.8% and the 10-year survival was 67.7% among patients with SSc vs 92.9% and 84.8%, respectively, for the comparators (P < 0.0001). The mortality rate in patients with SSc was 42.1 per 1000 person-years and 15.8 per 1000 person-years in their comparators, corresponding to an HR of 3.7 (95% CI 2.9, 4.7) at the end of the first year of follow-up and 2.0 (95% CI 1.4, 2.8) at the end of the follow-up period., Conclusion: Despite advances in understanding the disease and in diagnostic methods over the past decades, survival is still severely impacted in Swedish patients diagnosed with SSc between 2004 and 2015., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Background: Familial associations can be indicators of shared genetic susceptibility between two diseases. Previous data on familial autoimmunity in patients with idiopathic inflammatory myopathies (IIM) are scarce and inconsistent., Objectives: To investigate which autoimmune diseases (ADs) may share genetic susceptibility with IIM, we examined the familial associations between IIM and different ADs., Methods: In this Swedish population-based family study, we assembled 7615 first-degree relatives (FDRs) of 1620 patients with IIM and 37,309 relatives of 7797 matched individuals without IIM. Via register linkages, we ascertained rheumatoid arthritis, other rheumatic inflammatory diseases (RIDs), multiple sclerosis, inflammatory bowel diseases (IBD), type 1 diabetes mellitus, autoimmune thyroid diseases (AITD), coeliac disease (CeD) and myasthenia gravis among the FDRs. We estimated the familial association between IIM and each AD using conditional logistic regression and performed subgroup analyses by kinship., Results: Patients with IIM had significantly higher odds of having ≥1 FDR affected by other RIDs (adjusted odds ratio [aOR] = 1.40, 95% confidence interval [CI] 1.11-1.78) and greater odds of having ≥2 FDRs affected by CeD (aOR = 3.57, 95% CI 1.28-9.92) compared to the individuals without IIM. In the analyses of any FDR pairs, we observed familial associations for other RIDs (aOR = 1.34, 95% CI 1.14-1.56), IBD (aOR = 1.20, 95% CI 1.02-1.41), AITD (aOR = 1.10, 95% CI 1.02-1.19) and CeD (aOR = 1.37, 95% CI 1.08-1.74) while associations for other ADs were not statistically significant., Conclusion: The observed familial associations may suggest that IIM shares genetic susceptibility with various ADs, information that may be useful for clinical counselling and guiding future genetic studies of IIM., (© 2022 The Authors. Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.)

Objective: To examine how comorbidities in patients with early rheumatoid arthritis (RA) associate with use of different disease-modifying antirheumatic drugs (DMARDs)., Methods: We used Swedish nationwide clinical and quality registers to collect comorbidity data for patients diagnosed with RA during 2006-2019 (n=13 505). We compared the use of DMARDs at diagnosis and after 1 year, in relation to comorbidity categories 5 years prior to RA diagnosis and overall comorbidity burden. For each comorbidity category, we also calculated adjusted ORs of being on treatment with other (or no) DMARDs compared with methotrexate (MTX) monotherapy 1 year after RA diagnosis., Results: At RA diagnosis, 68% (n=9178) of all patients were treated with MTX monotherapy, with the lowest proportion in patients with chronic kidney (CKD, 48%, n=50) and respiratory diseases (57%, n=413). At 1 year, most patients still received MTX monotherapy (<11% decrease, across all comorbidity categories). At 1 year, 13% received biological/targeted synthetic DMARDs, with the lowest proportion among patients with malignant diseases (OR=0.69, 95% CI=0.51 to 0.95). Being without DMARD at 1 year was more common among patients with CKD (OR=3.25, 95% CI=2.20 to 4.81), respiratory diseases (OR=1.83, 95% CI=1.32 to 2.53) or a history of hospitalisation due to infection (OR=1.47, 95% CI=1.23 to 1.75), and among patients with higher comorbidity burden and older age., Conclusion: In a nationwide setting with universal healthcare, most comorbid conditions do not limit the initiation or continuation of MTX or other DMARDs in early RA, although patients with certain comorbid conditions, higher comorbidity burden and higher age were somewhat less intensively treated., Competing Interests: Competing interests: JA has received grants from Abbvie, AstraZeneca, BMS, Eli Lily, MSD, Pfizer, Roche, Samsung Bioepis, Sanofi and UCB; these entities have entered into agreements with Karolinska Institutet with JA as principal investigator, mainly in the context of safety monitoring of biologics via ARTIS/Swedish Biologics Register. SS is a part-time employee of deCODE genetics, unrelated to this work. The other authors have declared no conflicts of interest., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To explore physical activity patterns, including conditioning exercise and sport-specific training, and management routines utilized by handlers of Swedish sporting and working dogs participating in agility, obedience, rally obedience and working trial disciplines., Procedures: Dog handlers provided information on competition-level dogs through an internet-based cross-sectional and descriptive survey on physical activity, sport-specific training and management. Results are reported overall and stratified by participation in specific disciplines., Results: We received 1615 replies to the questionnaire. After data cleaning, 1582 dogs (98%) remained for the analysis. Of these, 430 participated in agility, 790 in obedience, 596 in rally obedience, and 847 dogs had competed in a working trial, i.e., messenger, protection, search or tracking. Number of disciplines performed by each dog varied between one and five. Most common was participation in one ( n = 767, 48%) or two ( n = 541, 34%) disciplines. Out of the dogs competing in one discipline, 38% ( n = 294) were considered to be specialized as they actively trained only that discipline for ≥10 months per year. The vast majority of the dogs ( n = 1129, 71%) received more than 1 h of daily physical activity, e.g., walks, and only n = 51 (3%) were never exercised off-leash. Preferred self-selected gait was trot ( n = 907, 57%) and gallop ( n = 499, 32%). A fifth ( n = 319, 20%) never played with other dogs. The majority ( n = 1328, 84%) received more than 1 h of vigorous physical conditioning exercise per week. Almost three quarters ( n = 1119, 71%) participated in physical conditioning exercise. Two thirds ( n = 953, 60%) participated in at least 3 h of sport-specific training per week and only a very small portion ( n = 35, 2%) trained their specific discipline less than once per week. Median total work load, i.e., all daily physical activity, vigorous physical conditioning exercise and sport-specific training, was 16.5 h per week., Conclusion and Clinical Relevance: We observe physical activity at moderate to high durations and moderate to vigorous intensities among Swedish sporting and working trial dogs. Most dogs received physical conditioning exercise, but not all dogs were warmed up before training and competition. Our study provides veterinary professionals and dog trainers with valuable insights on the physical exposures and management routines of sporting and working trial dogs., Competing Interests: Author AE was employed by Djurkliniken Gefle IVC Evidensia. Authors AH and CK were self-employed at EmpowerPhysio and Veterinär Catarina Kjellerstedt, respectively. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Essner, Hesbach, Igelström, Kjellerstedt, Svensson and Westerlind.)