| 1. |
- Murari, A., et al.
(författare)
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A control oriented strategy of disruption prediction to avoid the configuration collapse of tokamak reactors
- 2024
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Ingår i: Nature Communications. - 2041-1723 .- 2041-1723. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- The objective of thermonuclear fusion consists of producing electricity from the coalescence of light nuclei in high temperature plasmas. The most promising route to fusion envisages the confinement of such plasmas with magnetic fields, whose most studied configuration is the tokamak. Disruptions are catastrophic collapses affecting all tokamak devices and one of the main potential showstoppers on the route to a commercial reactor. In this work we report how, deploying innovative analysis methods on thousands of JET experiments covering the isotopic compositions from hydrogen to full tritium and including the major D-T campaign, the nature of the various forms of collapse is investigated in all phases of the discharges. An original approach to proximity detection has been developed, which allows determining both the probability of and the time interval remaining before an incoming disruption, with adaptive, from scratch, real time compatible techniques. The results indicate that physics based prediction and control tools can be developed, to deploy realistic strategies of disruption avoidance and prevention, meeting the requirements of the next generation of devices.
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| 5. |
- Blokland, G. A. M., et al.
(författare)
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Sex-Dependent Shared and Nonshared Genetic Architecture Across Mood and Psychotic Disorders
- 2022
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Ingår i: Biological Psychiatry. - : Elsevier BV. - 0006-3223 .- 1873-2402. ; 91:1, s. 102-117
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Tidskriftsartikel (refereegranskat)abstract
- Background: Sex differences in incidence and/or presentation of schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BIP) are pervasive. Previous evidence for shared genetic risk and sex differences in brain abnormalities across disorders suggest possible shared sex-dependent genetic risk. Methods: We conducted the largest to date genome-wide genotype-by-sex (G×S) interaction of risk for these disorders using 85,735 cases (33,403 SCZ, 19,924 BIP, and 32,408 MDD) and 109,946 controls from the PGC (Psychiatric Genomics Consortium) and iPSYCH. Results: Across disorders, genome-wide significant single nucleotide polymorphism–by-sex interaction was detected for a locus encompassing NKAIN2 (rs117780815, p = 3.2 × 10−8), which interacts with sodium/potassium-transporting ATPase (adenosine triphosphatase) enzymes, implicating neuronal excitability. Three additional loci showed evidence (p < 1 × 10−6) for cross-disorder G×S interaction (rs7302529, p = 1.6 × 10−7; rs73033497, p = 8.8 × 10−7; rs7914279, p = 6.4 × 10−7), implicating various functions. Gene-based analyses identified G×S interaction across disorders (p = 8.97 × 10−7) with transcriptional inhibitor SLTM. Most significant in SCZ was a MOCOS gene locus (rs11665282, p = 1.5 × 10−7), implicating vascular endothelial cells. Secondary analysis of the PGC-SCZ dataset detected an interaction (rs13265509, p = 1.1 × 10−7) in a locus containing IDO2, a kynurenine pathway enzyme with immunoregulatory functions implicated in SCZ, BIP, and MDD. Pathway enrichment analysis detected significant G×S interaction of genes regulating vascular endothelial growth factor receptor signaling in MDD (false discovery rate-corrected p < .05). Conclusions: In the largest genome-wide G×S analysis of mood and psychotic disorders to date, there was substantial genetic overlap between the sexes. However, significant sex-dependent effects were enriched for genes related to neuronal development and immune and vascular functions across and within SCZ, BIP, and MDD at the variant, gene, and pathway levels. © 2021 Society of Biological Psychiatry
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| 11. |
- Escartin, C., et al.
(författare)
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Reactive astrocyte nomenclature, definitions, and future directions
- 2021
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Ingår i: Nature Neuroscience. - : Springer Science and Business Media LLC. - 1097-6256 .- 1546-1726. ; 24, s. 312-325
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Tidskriftsartikel (refereegranskat)abstract
- Reactive astrocytes are astrocytes undergoing morphological, molecular, and functional remodeling in response to injury, disease, or infection of the CNS. Although this remodeling was first described over a century ago, uncertainties and controversies remain regarding the contribution of reactive astrocytes to CNS diseases, repair, and aging. It is also unclear whether fixed categories of reactive astrocytes exist and, if so, how to identify them. We point out the shortcomings of binary divisions of reactive astrocytes into good-vs-bad, neurotoxic-vs-neuroprotective or A1-vs-A2. We advocate, instead, that research on reactive astrocytes include assessment of multiple molecular and functional parameters-preferably in vivo-plus multivariate statistics and determination of impact on pathological hallmarks in relevant models. These guidelines may spur the discovery of astrocyte-based biomarkers as well as astrocyte-targeting therapies that abrogate detrimental actions of reactive astrocytes, potentiate their neuro- and glioprotective actions, and restore or augment their homeostatic, modulatory, and defensive functions. Good-bad binary classifications fail to describe reactive astrocytes in CNS disorders. Here, 81 researchers reach consensus on widespread misconceptions and provide definitions and recommendations for future research on reactive astrocytes.
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| 12. |
- Gaulton, Kyle J, et al.
(författare)
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Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci.
- 2015
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 47:12, s. 1415-1415
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Tidskriftsartikel (refereegranskat)abstract
- We performed fine mapping of 39 established type 2 diabetes (T2D) loci in 27,206 cases and 57,574 controls of European ancestry. We identified 49 distinct association signals at these loci, including five mapping in or near KCNQ1. 'Credible sets' of the variants most likely to drive each distinct signal mapped predominantly to noncoding sequence, implying that association with T2D is mediated through gene regulation. Credible set variants were enriched for overlap with FOXA2 chromatin immunoprecipitation binding sites in human islet and liver cells, including at MTNR1B, where fine mapping implicated rs10830963 as driving T2D association. We confirmed that the T2D risk allele for this SNP increases FOXA2-bound enhancer activity in islet- and liver-derived cells. We observed allele-specific differences in NEUROD1 binding in islet-derived cells, consistent with evidence that the T2D risk allele increases islet MTNR1B expression. Our study demonstrates how integration of genetic and genomic information can define molecular mechanisms through which variants underlying association signals exert their effects on disease.
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| 13. |
- Acosta-Herrera, M, et al.
(författare)
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Genome-wide meta-analysis reveals shared new loci in systemic seropositive rheumatic diseases
- 2019
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Ingår i: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 78:3, s. 311-319
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Tidskriftsartikel (refereegranskat)abstract
- Immune-mediated inflammatory diseases (IMIDs) are heterogeneous and complex conditions with overlapping clinical symptoms and elevated familial aggregation, which suggests the existence of a shared genetic component. In order to identify this genetic background in a systematic fashion, we performed the first cross-disease genome-wide meta-analysis in systemic seropositive rheumatic diseases, namely, systemic sclerosis, systemic lupus erythematosus, rheumatoid arthritis and idiopathic inflammatory myopathies.MethodsWe meta-analysed ~6.5 million single nucleotide polymorphisms in 11 678 cases and 19 704 non-affected controls of European descent populations. The functional roles of the associated variants were interrogated using publicly available databases.ResultsOur analysis revealed five shared genome-wide significant independent loci that had not been previously associated with these diseases: NAB1, KPNA4-ARL14, DGQK, LIMK1 and PRR12. All of these loci are related with immune processes such as interferon and epidermal growth factor signalling, response to methotrexate, cytoskeleton dynamics and coagulation cascade. Remarkably, several of the associated loci are known key players in autoimmunity, which supports the validity of our results. All the associated variants showed significant functional enrichment in DNase hypersensitivity sites, chromatin states and histone marks in relevant immune cells, including shared expression quantitative trait loci. Additionally, our results were significantly enriched in drugs that are being tested for the treatment of the diseases under study.ConclusionsWe have identified shared new risk loci with functional value across diseases and pinpoint new potential candidate loci that could be further investigated. Our results highlight the potential of drug repositioning among related systemic seropositive rheumatic IMIDs.
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- Pironi, L., et al.
(författare)
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Clinical classification of adult patients with chronic intestinal failure due to benign disease: An international multicenter cross-sectional survey
- 2018
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Ingår i: Clinical Nutrition. - : Elsevier BV. - 0261-5614. ; 37:2, s. 728-738
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Tidskriftsartikel (refereegranskat)abstract
- Background & aims: The aim of the study was to evaluate the applicability of the ESPEN 16-category clinical classification of chronic intestinal failure, based on patients' intravenous supplementation (IVS) requirements for energy and fluids, and to evaluate factors associated with those requirements. Methods: ESPEN members were invited to participate through ESPEN Council representatives. Participating centers enrolled adult patients requiring home parenteral nutrition for chronic intestinal failure on March 1st 2015. The following patient data were recorded though a structured database: sex, age, body weight and height, intestinal failure mechanism, underlying disease, IVS volume and energy need. Results: Sixty-five centers from 22 countries enrolled 2919 patients with benign disease. One half of the patients were distributed in 3 categories of the ESPEN clinical classification. 9% of patients required only fluid and electrolyte supplementation. IVS requirement varied considerably according to the pathophysiological mechanism of intestinal failure. Notably, IVS volume requirement represented loss of intestinal function better than IVS energy requirement. A simplified 8 category classification of chronic intestinal failure was devised, based on two types of IVS (either fluid and electrolyte alone or parenteral nutrition admixture containing energy) and four categories of volume. Conclusions: Patients' IVS requirements varied widely, supporting the need for a tool to homogenize patient categorization. This study has devised a novel, simplified eight category IVS classification for chronic intestinal failure that will prove useful in both the clinical and research setting when applied together with the underlying pathophysiological mechanism of the patient's intestinal failure. (C) 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.
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| 24. |
- Scahill, R. I., et al.
(författare)
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Biological and clinical characteristics of gene carriers far from predicted onset in the Huntington?s disease Young Adult Study (HD-YAS): a cross-sectional analysis
- 2020
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Ingår i: Lancet Neurology. - : Elsevier BV. - 1474-4422. ; 19:6, s. 502-512
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Tidskriftsartikel (refereegranskat)abstract
- Background Disease-modifying treatments are in development for Huntington's disease; crucial to their success is to identify a timepoint in a patient's life when there is a measurable biomarker of early neurodegeneration while clinical function is still intact. We aimed to identify this timepoint in a novel cohort of young adult premanifest Huntington's disease gene carriers (preHD) far from predicted clinical symptom onset. Methods We did the Huntington's disease Young Adult Study (HD-YAS) in the UK. We recruited young adults with preHD and controls matched for age, education, and sex to ensure each group had at least 60 participants with imaging data, accounting for scan fails. Controls either had a family history of Huntington's disease but a negative genetic test, or no known family history of Huntington's disease. All participants underwent detailed neuropsychiatric and cognitive assessments, including tests from the Cambridge Neuropsychological Test Automated Battery and a battery assessing emotion, motivation, impulsivity and social cognition (EMOTICOM). Imaging (done for all participants without contraindications) included volumetric MRI, diffusion imaging, and multiparametric mapping. Biofluid markers of neuronal health were examined using blood and CSF collection. We did a cross-sectional analysis using general least-squares linear models to assess group differences and associations with age and CAG length, relating to predicted years to clinical onset. Results were corrected for multiple comparisons using the false discovery rate (FDR), with FDR <0.05 deemed a significant result. Findings Data were obtained between Aug 2, 2017, and April 25, 2019. We recruited 64 young adults with preHD and 67 controls. Mean ages of participants were 29.0 years (SD 5.6) and 29.1 years (5.7) in the preHD and control groups, respectively. We noted no significant evidence of cognitive or psychiatric impairment in preHD participants 23.6 years (SD 5.8) from predicted onset (FDR 0.22-0.87 for cognitive measures, 0.31-0.91 for neuropsychiatric measures). The preHD cohort had slightly smaller putamen volumes (FDR=0.03), but this did not appear to be closely related to predicted years to onset (FDR=0.54). There were no group differences in other brain imaging measures (FDR >0.16). CSF neurofilament light protein (NfL), plasma NfL, and CSF YKL-40 were elevated in this far-from-onset preHD cohort compared with controls (FDR<0.0001, =0.01, and =0.03, respectively). CSF NfL elevations were more likely in individuals closer to expected clinical onset (FDR <0.0001). Interpretation We report normal brain function yet a rise in sensitive measures of neurodegeneration in a preHD cohort approximately 24 years from predicted clinical onset. CSF NfL appears to be a more sensitive measure than plasma NfL to monitor disease progression. This preHD cohort is one of the earliest yet studied, and our findings could be used to inform decisions about when to initiate a potential future intervention to delay or prevent further neurodegeneration while function is intact.
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| 25. |
- Tahmasian, Masoud, et al.
(författare)
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ENIGMA-Sleep : Challenges, opportunities, and the road map
- 2021
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Ingår i: Journal of Sleep Research. - : Wiley. - 0962-1105 .- 1365-2869. ; 30:6
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Forskningsöversikt (refereegranskat)abstract
- Neuroimaging and genetics studies have advanced our understanding of the neurobiology of sleep and its disorders. However, individual studies usually have limitations to identifying consistent and reproducible effects, including modest sample sizes, heterogeneous clinical characteristics and varied methodologies. These issues call for a large-scale multi-centre effort in sleep research, in order to increase the number of samples, and harmonize the methods of data collection, preprocessing and analysis using pre-registered well-established protocols. The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) consortium provides a powerful collaborative framework for combining datasets across individual sites. Recently, we have launched the ENIGMA-Sleep working group with the collaboration of several institutes from 15 countries to perform large-scale worldwide neuroimaging and genetics studies for better understanding the neurobiology of impaired sleep quality in population-based healthy individuals, the neural consequences of sleep deprivation, pathophysiology of sleep disorders, as well as neural correlates of sleep disturbances across various neuropsychiatric disorders. In this introductory review, we describe the details of our currently available datasets and our ongoing projects in the ENIGMA-Sleep group, and discuss both the potential challenges and opportunities of a collaborative initiative in sleep medicine.
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| 27. |
- Aoude, M., et al.
(författare)
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TREATMENT PATTERNS OF IDIOPATHIC INFLAMMATORY MYOPATHIES : RESULTS FROM AN INTERNATIONAL COHORT OF OVER 1,400 PATIENTS
- 2022
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Ingår i: Annals of the Rheumatic Diseases. - : HighWire Press. - 0003-4967 .- 1468-2060. ; 81:Suppl. 1, s. 105-106
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Idiopathic inflammatory myopathies (IIM) are a group of heterogeneous autoimmune disorders with limited standardization of treatment protocols.ObjectivesTo evaluate frequency and patterns of various treatments used for IIM based on disease subtype, world region, and organ involvement.MethodsCross-sectional data from the international CoVAD self-report e-survey1 was extracted on Sep 14th, 2021. Patient details included demographics, IIM subtypes (dermatomyositis (DM), polymyositis (PM), inclusion body myositis (IBM), antisynthetase syndrome (ASSD), necrotizing myositis (NM) and overlap myositis (OM)), clinical symptoms, disease duration and activity, and current treatments. Treatments were categorized in corticosteroids (CS), antimalarials, immunosuppressants (IS), intravenous immunoglobulins (IVIG), biologics, and others. Typical clinical symptoms (dyspnea, dysphagia) were used as surrogate for organ involvement. Factors associated with IS were analyzed using multivariable logistic regression, adjusting for IIM subtype, demographics, world region, disease activity, and prevalent clinical symptoms (>10%).ResultsIn 1418 patients with IIM, median age was 61 years [IQR 49-70], 62.5% were females, median disease duration was 6 years [IQR 3-11], most common subset was DM (32.4%).The most used treatments were IS (49.4%, including Methotrexate 19.6%, Mycophenolate Mofetil 18.2%, Azathioprine 8.8%, Cyclosporine 2.7%, Tacrolimus 2%, Leflunomide 1.6%, Sulfasalazine 1%, and Cyclophosphamide 0.6%), followed by CS (40.8%), antimalarials (13.8%) and IVIG (9.4%). Biologics were used in 4.3% of patients.Treatment patterns differed significantly by IIM subtypes with a higher frequency of IS (77.7%) and CS (63.4%) use in ASSD; antimalarials (28.6%) and biologics (9.8%) use in OM and IVIG use in NM (24.6%) (Table 1). Also, treatment patterns were different in regions of the world (Figure 1), with a higher frequency of CS use in Europe (60.5%) and IS use in South America (77.2%). Antimalarials were most used in Asia (19.4%), while IVIG use was most common in Oceania (16.9%). Dyspnea was associated with higher use of IS (69.9%) and CS (65.8%) (p<0.001), whereas dysphagia was negatively associated with IS (39.7%) and CS (32.7%) likely due to a higher proportion in IBM patients reporting dysphagia.Table 1.Current Treatments for IIM, Stratified by Disease SubtypesDermatomyositisPolymyositisInclusion Body MyositisAnti-synthetase syndromeNecrotizing myositisOverlap syndromeAll IIMp-valueNumber of patients459182348148572241418Immunosuppressants*269 (58.6)107 (58.8)39 (11.2)115 (77.7)40 (70.2)130 (58.0)700 (49.4)<0.001Corticosteroids208 (48.0)81 (46.8)32 (9.7)90 (63.4)32 (59.3)103 (50.0)546 (40.8)<0.001Antimalarials99 (21.6)7 (3.8)0 (0.0)25 (16.9)1 (1.8)64 (28.6)196 (13.8)<0.001Intravenous Immunoglobulins54 (11.8)16 (8.8)19 (5.5)10 (6.8)14 (24.6)20 (8.9)133 (9.4)<0.001Biologics**17 (3.7)7 (3.8)0 (0.0)13 (8.8)2 (3.5)22 (9.8)61 (4.3)<0.001Others***6 (1.3)0 (0.0)0 (0.0)1 (0.7)0 (0.0)5 (2,2)12 (0.8)0.098*Methotrexate (278), Mycophenolate Mofetil (258), Azathioprine (125), Cyclosporine (38), Tacrolimus (28), Leflunomide (23), Sulfasalazine (14), Cyclophosphamide (9). **Rituximab (44), Abatacept (5), TNF inhibitors (4), Tocilizumab (3), Belimumab (3), Secukinumab (1). ***JAK(10) and PDE4 inhibitors (2)Multivariable logistic regression analysis showed an association of IS with the IIM subtype (least used in IBM (OR 0.07 [95%CI 0.04-0.13] compared to DM), world region (most used in South America (OR 2.35 [1.12-4.91] compared to North America), active and worsening disease activity (OR 3.49 [1.76-6.91] compared to remission), and some clinical features (dyspnea, fatigue, and muscle weakness).ConclusionIIM treatment patterns differ significantly by disease subtypes, world regions and organ involvement, highlighting the need for unified international consensus-driven guidelines.References[1]Parikshit S. et al. Rheumatol Int. 2022 Jan;42(1):23–9.Disclosure of InterestsNone declared
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| 31. |
- Grignaschi, S., et al.
(författare)
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HIGH FATIGUE SCORES IN PATIENTS WITH IDIOPATHIC INFLAMMATORY MYOPATHIES : A MULTIGROUP COMPARATIVE STUDY FROM THE COVAD E-SURVEY
- 2022
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Ingår i: Annals of the Rheumatic Diseases. - : HighWire Press. - 0003-4967 .- 1468-2060. ; 81:Suppl. 1, s. 748-748
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Idiopathic inflammatory myopathies (IIM) are a rare, multisystem, heterogeneous diseases, and contribute to high psychological burden. The patients’ perception of physical health, deteriorating independence and social and environmental relationships may not always be a direct function of disease activity. To face with these aspects, several worldwide specialized organization have recommended the use of patient reported outcome measures (PROMs) both in clinical trials and observational studies to highlight patient’s perception of the disease (1). Unfortunately, data on fatigue scores in IIM is limited.ObjectivesWe compared fatigue VAS scores in patients with IIM, autoimmune diseases (AIDs) and healthy controls (HCs) and triangulated them with PROMIS physical function in a large international cohort made up of answers from the e-survey regarding the COVID-19 Vaccination in Autoimmune Diseases (COVAD) study.MethodsData of 16327 respondents was extracted from the COVAD database on August 31th 2021. VAS fatigue scores were compared between AID, HC and IIM using univariate followed by multivariate analysis after adjusting for baseline differences. We further performed a propensity score matched analysis on 1827 subjects after adjusting for age, gender and ethnicity. The Kruskal-Wallis test was used for continuous variables and chi-square test for categorical variables, and Bonferroni’s correction was applied for the post hoc analyses considering IIMs as a reference group.ResultsWe analyzed answers from 6988 patients, with a mean age of 43.8 years (SD 16.2). The overall percentage of female was 72% and the population ethnicity was mainly composed of White (55.1%), followed by Asian (24.6%), and Hispanic (13.8%). The overall fatigue VAS was 3.6 mm (SD 2.7). IIMs VAS was 4.8 mm (SD 2.6), AIDs 4.5 mm (SD 2.6), and HC 2.8 mm (SD 2.6) (P <0,001). VAS fatigue scores of IIMs were comparable with AIDs (P 0.084), albeit significantly higher than the HCs (P <0,001). Notably, fatigue VAS was lower in IIMs than AIDs in two distinct subsets: inactive disease as defined by the patient’s perception and the “excellent” general health condition group, where IIMs had worse scores (P <0,05). Interestingly, fatigue VAS was comparable in active disease defined by physician assessment, patient perception, based on general functional status, or when defined by steroid dose being prescribed. Notably, after propensity matched analysis of patients adjusting for gender, age and ethnicity (1.827 answers, i.e. 609 subjects per group, P =1) the differences disappeared and IIMs and AIDs had comparable fatigue levels across all levels of disease activity, although the fatigue discrepancies with HCs were substantially confirmed.After application of a multivariate linear regression analysis we found that lower fatigue VAS scores were related to HC (P <0,001), male gender (P <0,001), Asian and Hispanic ethnicities (P <0,001 and 0,003).ConclusionOur study confirms that there is a higher prevalence of fatigue in all the AIDs patients, with comparable VAS scores between IIMs and other AIDs. We can also read our data commenting that females and/or Caucasians patients suffer a higher impact of this manifestation of chronic autoimmune diseases upon their lives. This is why these subjects, to our judgement, should be carefully evaluated during outpatients visits and to whom we should spend some extra time to discuss health related issues and how to improve them.References[1]Regardt, M. et al. OMERACT 2018 Modified Patient-reported Outcome Domain Core Set in the Life Impact Area for Adult Idiopathic Inflammatory Myopathies. J. Rheumatol.46, 1351–1354 (2019).Figure 1.distribution of Fatigue VAS scores in the three population evaluated. IIM idiopathic inflammatory myositis; AID autoimmune diseases; HC healthy controls; * P < 0,05.Disclosure of InterestsNone declared
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| 32. |
- Gupta, L., et al.
(författare)
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COVID-19 SEVERITY AND VACCINE BREAKTHROUGH INFECTIONS IN IDIOPATHIC INFLAMMATORY MYOPATHIES, OTHER SYSTEMIC AUTOIMMUNE AND INFLAMMATORY DISEASES, AND HEALTHY INDIVIDUALS : RESULTS FROM THE COVID-19 VACCINATION IN AUTOIMMUNE DISEASES (COVAD) STUDY.
- 2022
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Ingår i: Annals of the Rheumatic Diseases. - : HighWire Press. - 0003-4967 .- 1468-2060. ; 81:Suppl. 1, s. 334-336
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Significant gaps are present in the evidence of the spectrum and severity of COVID-19 infection in idiopathic inflammatory myopathies (IIM). IIM patients typically require immunosuppressive therapy, may have multiple disease sequelae, and frequent comorbidities, and thus may be more susceptible to severe COVID-19 infection and complications (1). The possibility of attenuated immunogenicity and reduced efficacy of COVID-19 vaccines due to concomitant immunosuppressive medication is a major concern in these patients, and there is little data available on COVID-19 vaccine breakthrough infections (BI) in IIM (2).ObjectivesThis study aimed to compare disease spectrum and severity and COVID-19 BI in patients with IIM, other systemic autoimmune and inflammatory diseases (SAIDs) and healthy controls (HCs).MethodsWe developed an extensive self-reporting electronic-survey (COVAD survey) featuring 36 questions to collect respondent demographics, SAID details, COVID-19 infection history, COVID-19 vaccination details, 7-day post vaccination adverse events and patient reported outcome measures using the PROMIS tool. After pilot testing, validation, translation into 18 languages on the online platform surveymonkey.com, and vetting by international experts, the COVAD survey was circulated in early 2021 by a multicenter study group of >110 collaborators in 94 countries. BI was defined as COVID-19 infection occurring more than 2 weeks after receiving 1st or 2nd dose of a COVID-19 vaccine. We analyzed data from the baseline survey for descriptive and intergroup comparative statistics based on data distribution and variable type.Results10900 respondents [mean age 42 (30-55) years, 74% females and 45% Caucasians] were analyzed. 1,227 (11.2%) had IIM, 4,640 (42.6%) had other SAIDs, and 5,033 (46.2%) were HC. All respondents included in the final analysis had received a single dose of the vaccine and 69% had received 2 primary doses. Pfizer (39.8%) was the most common vaccine received, followed by Oxford/AstraZeneca (13.4%), and Covishield (10.9%). IIM patients were older, had a higher Caucasian representation and higher Pfizer uptake than other SAIDs, and HC. A higher proportion of IIM patients received immunosuppressants than other SAIDs.IIMs were at a lower risk of symptomatic pre-vaccination COVID-19 infection compared to SAIDs [multivariate OR 0.6 (0.4-0.8)] and HCs [multivariate OR 0.39 (0.28-0.54)], yet at a higher risk of hospitalization due to COVID-19 compared to SAIDs [univariate OR 2.3 (1.2-3.5)] and HCs [multivariate OR 2.5 (1.1-5.8)]. BIs were very uncommon in IIM patients, with only 17 (1.4%) reporting BI. IIM patients were at a higher risk of contracting COVID-19 prior to vaccination than ≤2 weeks of vaccination [univariate OR 8 (4.1-15)] or BI [univariate OR 4.6 (2.7-8.0)]. BIs were equally severe compared to when they occurred prior to vaccination in IIMs, and were comparable between IIM, SAIDs, and HC (Figure 1), though BI disease duration was shorter in IIMs than SAIDs (7 vs 11 days, p 0.027). 13/17 IIM patients with BI were on immunosuppressants.ConclusionIIM patients experienced COVID-19 infection less frequently prior to vaccination but were at a higher risk of hospitalization and requirement for oxygen therapy compared with patients with HC. Breakthrough COVID-19 infections were rare (1.4%) in vaccinated IIM patients, and were similar to HC and SAIDs, except for shorter disease duration in IIM.References[1]Brito-Zerón P, Sisó-Almirall A, Flores-Chavez A, Retamozo S, Ramos-Casals M. SARS-CoV-2 infection in patients with systemic autoimmune diseases. Clin Exp Rheumatol. 2021 Jun;39(3):676–87.[2]Wack S, Patton T, Ferris LK. COVID-19 vaccine safety and efficacy in patients with immune-mediated inflammatory disease: Review of available evidence. J Am Acad Dermatol. 2021 Nov;85(5):1274–84.AcknowledgementsThe authors thank all members of the COVAD study group for their invaluable role in the collection of data. The authors thank all respondents for filling the questionnaire. The authors thank The Myositis Association, Myositis India, Myositis UK, the Myositis Global Network, Cure JM, Cure IBM, Sjögren’s India Foundation, EULAR PARE, and various other patient support groups and organizations for their invaluable contribution in the dissemination of this survey among patients which made the data collection possible. The authors also thank all members of the COVAD study group.Disclosure of InterestsLatika Gupta: None declared, Leonardo Santos Hoff: None declared, Naveen R: None declared, Parikshit Sen: None declared, Samuel Katsuyuki Shinjo: None declared, Jessica Day Grant/research support from: JD has received research funding from CSL Limited, James B. Lilleker: None declared, Vishwesh Agarwal: None declared, Sinan Kardes: None declared, Minchul Kim: None declared, Ashima Makol: None declared, Marcin Milchert: None declared, Tamer A Gheita: None declared, Babur Salim: None declared, Tsvetelina Velikova: None declared, Abraham Edgar Gracia-Ramos: None declared, Ioannis Parodis Speakers bureau: IP has received research funding and/or honoraria from Amgen, AstraZeneca, Aurinia Pharmaceuticals, Elli Lilly and Company, Gilead Sciences, GlaxoSmithKline, Janssen Pharmaceuticals, Novartis and F. Hoffmann-La Roche AG., Consultant of: IP has received research funding and/or honoraria from Amgen, AstraZeneca, Aurinia Pharmaceuticals, Elli Lilly and Company, Gilead Sciences, GlaxoSmithKline, Janssen Pharmaceuticals, Novartis and F. Hoffmann-La Roche AG., Grant/research support from: IP has received research funding and/or honoraria from Amgen, AstraZeneca, Aurinia Pharmaceuticals, Elli Lilly and Company, Gilead Sciences, GlaxoSmithKline, Janssen Pharmaceuticals, Novartis and F. Hoffmann-La Roche AG., Albert Selva-O’Callaghan: None declared, Elena Nikiphorou Speakers bureau: EN has received speaker honoraria/participated in advisory boards for Celltrion, Pfizer, Sanofi, Gilead, Galapagos, AbbVie, Lilly, Consultant of: EN has received speaker honoraria/participated in advisory boards for Celltrion, Pfizer, Sanofi, Gilead, Galapagos, AbbVie, Lilly, Grant/research support from: EN holds research grants from Pfizer and Lilly., Tulika Chatterjee: None declared, Ai Lyn Tan Speakers bureau: ALT has received honoraria for advisory boards and speaking for Abbvie, Gilead, Janssen, Lilly, Novartis, Pfizer, UCB., Consultant of: ALT has received honoraria for advisory boards and speaking for Abbvie, Gilead, Janssen, Lilly, Novartis, Pfizer, UCB., Arvind Nune: None declared, Lorenzo Cavagna: None declared, Miguel A Saavedra: None declared, Nelly Ziade Speakers bureau: NZ has received speaker fees, advisory board fees and research grants from Pfizer, Roche, Abbvie, Eli Lilly, NewBridge, Sanofi-Aventis, Boehringer Ingelheim, Janssen, Pierre Fabre; none is related to this manuscript, Consultant of: NZ has received speaker fees, advisory board fees and research grants from Pfizer, Roche, Abbvie, Eli Lilly, NewBridge, Sanofi-Aventis, Boehringer Ingelheim, Janssen, Pierre Fabre; none is related to this manuscript, Grant/research support from: NZ has received speaker fees, advisory board fees and research grants from Pfizer, Roche, Abbvie, Eli Lilly, NewBridge, Sanofi-Aventis, Boehringer Ingelheim, Janssen, Pierre Fabre; none is related to this manuscript, Johannes Knitza: None declared, Masataka Kuwana: None declared, Oliver Distler Speakers bureau: OD has/had consultancy relationship with and/or has received research funding from or has served as a speaker for the following companies in the area of potential treatments for systemic sclerosis and its complications in the last three years: Abbvie, Acceleron, Alcimed, Amgen, AnaMar, Arxx, Baecon, Blade, Bayer, Boehringer Ingelheim, ChemomAb, Corbus, CSL Behring, Galapagos, Glenmark, GSK, Horizon (Curzion), Inventiva, iQvia, Kymera, Lupin, Medac, Medscape, Mitsubishi Tanabe, Novartis, Roche, Roivant, Sanofi, Serodapharm, Topadur and UCB. Patent issued “mir-29 for the treatment of systemic sclerosis” (US8247389, EP2331143)., Consultant of: OD has/had consultancy relationship with and/or has received research funding from or has served as a speaker for the following companies in the area of potential treatments for systemic sclerosis and its complications in the last three years: Abbvie, Acceleron, Alcimed, Amgen, AnaMar, Arxx, Baecon, Blade, Bayer, Boehringer Ingelheim, ChemomAb, Corbus, CSL Behring, Galapagos, Glenmark, GSK, Horizon (Curzion), Inventiva, iQvia, Kymera, Lupin, Medac, Medscape, Mitsubishi Tanabe, Novartis, Roche, Roivant, Sanofi, Serodapharm, Topadur and UCB. Patent issued “mir-29 for the treatment of systemic sclerosis” (US8247389, EP2331143)., Grant/research support from: OD has/had consultancy relationship with and/or has received research funding from or has served as a speaker for the following companies in the area of potential treatments for systemic sclerosis and its complications in the last three years: Abbvie, Acceleron, Alcimed, Amgen, AnaMar, Arxx, Baecon, Blade, Bayer, Boehringer Ingelheim, ChemomAb, Corbus, CSL Behring, Galapagos, Glenmark, GSK, Horizon (Curzion), Inventiva, iQvia, Kymera, Lupin, Medac, Medscape, Mitsubishi Tanabe, Novartis, Roche, Roivant, Sanofi, Serodapharm, Topadur and UCB. Patent issued “mir-29 for the treatment of systemic sclerosis” (US8247389, EP2331143)., Hector Chinoy Speakers bureau: HC has been a speaker for UCB, Biogen., Consultant of: HC has received consulting fees from Novartis, Eli Lilly, Orphazyme, Astra Zeneca, Grant/research support from: HC has received grant support from Eli Lilly and UCB, Vikas Agarwal: None declared, Rohit Aggarwal Consultant of: RA has/had a consultancy relationship with and/or has received research funding from the following companies-Bristol Myers-Squibb, Pfizer, Genentech, Octapharma, CSL Behring, Mallinckrodt, AstraZeneca, Corbus, Kezar, and Abbvie, Janssen, Alexion, Argenx, Q32
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| 35. |
- Rothwell, S, et al.
(författare)
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Focused HLA analysis in Caucasians with myositis identifies significant associations with autoantibody subgroups
- 2019
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Ingår i: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 78:7, s. 996-1002
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Tidskriftsartikel (refereegranskat)abstract
- Idiopathic inflammatory myopathies (IIM) are a spectrum of rare autoimmune diseases characterised clinically by muscle weakness and heterogeneous systemic organ involvement. The strongest genetic risk is within the major histocompatibility complex (MHC). Since autoantibody presence defines specific clinical subgroups of IIM, we aimed to correlate serotype and genotype, to identify novel risk variants in the MHC region that co-occur with IIM autoantibodies.MethodsWe collected available autoantibody data in our cohort of 2582 Caucasian patients with IIM. High resolution human leucocyte antigen (HLA) alleles and corresponding amino acid sequences were imputed using SNP2HLA from existing genotyping data and tested for association with 12 autoantibody subgroups.ResultsWe report associations with eight autoantibodies reaching our study-wide significance level of p<2.9×10–5. Associations with the 8.1 ancestral haplotype were found with anti-Jo-1 (HLA-B*08:01, p=2.28×10–53 and HLA-DRB1*03:01, p=3.25×10–9), anti-PM/Scl (HLA-DQB1*02:01, p=1.47×10–26) and anti-cN1A autoantibodies (HLA-DRB1*03:01, p=1.40×10–11). Associations independent of this haplotype were found with anti-Mi-2 (HLA-DRB1*07:01, p=4.92×10–13) and anti-HMGCR autoantibodies (HLA-DRB1*11, p=5.09×10–6). Amino acid positions may be more strongly associated than classical HLA associations; for example with anti-Jo-1 autoantibodies and position 74 of HLA-DRB1 (p=3.47×10–64) and position 9 of HLA-B (p=7.03×10–11). We report novel genetic associations with HLA-DQB1 anti-TIF1 autoantibodies and identify haplotypes that may differ between adult-onset and juvenile-onset patients with these autoantibodies.ConclusionsThese findings provide new insights regarding the functional consequences of genetic polymorphisms within the MHC. As autoantibodies in IIM correlate with specific clinical features of disease, understanding genetic risk underlying development of autoantibody profiles has implications for future research.
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| 39. |
- Cornwall, L. A., et al.
(författare)
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Authentication and authorization mechanisms for multi-domain grid environments
- 2004
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Ingår i: Journal of Grid Computing. - : Springer Science and Business Media LLC. - 1570-7873 .- 1572-9184. ; 2:4, s. 301-311
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Tidskriftsartikel (refereegranskat)abstract
- This article discusses the authentication and the authorization aspects of security in grid environments spanning multiple administrative domains. Achievements in these areas are presented using the EU DataGrid project as an example implementation. It also gives an outlook on future directions of development.
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| 40. |
- de Vries, Petrus J, et al.
(författare)
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Natural clusters of tuberous sclerosis complex (TSC)-associated neuropsychiatric disorders (TAND) : new findings from the TOSCA TAND research project
- 2020
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Ingår i: Journal of Neurodevelopmental Disorders. - : Springer Science and Business Media LLC. - 1866-1955 .- 1866-1947. ; 12:1, s. 24-24
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Tuberous sclerosis complex (TSC)-associated neuropsychiatric disorders (TAND) have unique, individual patterns that pose significant challenges for diagnosis, psycho-education, and intervention planning. A recent study suggested that it may be feasible to use TAND Checklist data and data-driven methods to generate natural TAND clusters. However, the study had a small sample size and data from only two countries. Here, we investigated the replicability of identifying natural TAND clusters from a larger and more diverse sample from the TOSCA study.METHODS: As part of the TOSCA international TSC registry study, this embedded research project collected TAND Checklist data from individuals with TSC. Correlation coefficients were calculated for TAND variables to generate a correlation matrix. Hierarchical cluster and factor analysis methods were used for data reduction and identification of natural TAND clusters.RESULTS: A total of 85 individuals with TSC (female:male, 40:45) from 7 countries were enrolled. Cluster analysis grouped the TAND variables into 6 clusters: a scholastic cluster (reading, writing, spelling, mathematics, visuo-spatial difficulties, disorientation), a hyperactive/impulsive cluster (hyperactivity, impulsivity, self-injurious behavior), a mood/anxiety cluster (anxiety, depressed mood, sleep difficulties, shyness), a neuropsychological cluster (attention/concentration difficulties, memory, attention, dual/multi-tasking, executive skills deficits), a dysregulated behavior cluster (mood swings, aggressive outbursts, temper tantrums), and an autism spectrum disorder (ASD)-like cluster (delayed language, poor eye contact, repetitive behaviors, unusual use of language, inflexibility, difficulties associated with eating). The natural clusters mapped reasonably well onto the six-factor solution generated. Comparison between cluster and factor solutions from this study and the earlier feasibility study showed significant similarity, particularly in cluster solutions.CONCLUSIONS: Results from this TOSCA research project in an independent international data set showed that the combination of cluster analysis and factor analysis may be able to identify clinically meaningful natural TAND clusters. Findings were remarkably similar to those identified in the earlier feasibility study, supporting the potential robustness of these natural TAND clusters. Further steps should include examination of larger samples, investigation of internal consistency, and evaluation of the robustness of the proposed natural clusters.
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| 41. |
- El-Saadi, O, et al.
(författare)
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Paternal and maternal age as risk factors for psychosis: findings from Denmark, Sweden and Australia
- 2004
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Ingår i: Schizophrenia Research. - 0920-9964. ; 67:2-3, s. 227-236
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Tidskriftsartikel (refereegranskat)abstract
- Background: While the association between increased maternal age and congenital disorders has long been recognized, the offspring of older fathers are also at increased risk of congenital disorders related to DNA errors during spermatogenesis. Recent studies have drawn attention to an association between increased paternal age and increased risk of schizophrenia. The aim of the current study was to examine both paternal and maternal age as risk factors for the broader category of psychosis. Method: We used data from three sources examining psychosis: a population-based cohort study (Denmark), and two case-control studies (Sweden and Australia). Results: When controlling for the effect of maternal age, increased paternal age was significantly associated with increased risk of psychosis in the Danish and Swedish studies. The Australian study found no association between adjusted paternal age and risk of psychosis. When controlling for the effect of paternal age, younger maternal a-e was associated with an increased risk of psychoses in the Danish study alone. Conclusions: The offspring of older fathers are at increased risk of developing psychosis. The role of paternally derived mutations and/or psychosocial factors associated with older paternal age warrants further research. (C) 2003 Elsevier B.V. All rights reserved.
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| 42. |
- Greaves, Deborah, et al.
(författare)
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Environmental Impact Assessment : Gathering experiences from wave energy test centres in Europe
- 2016
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Ingår i: International Journal of Marine Energy. - : Elsevier BV. - 2214-1669. ; 14, s. 68-79
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Tidskriftsartikel (refereegranskat)abstract
- The wave energy industry is an emerging sector and a new user of maritime space that has potential to contribute significantly to the EU renewable energy goals. International and national regulatory frameworks necessitate Environmental Impact Assessments (EIA) that provide important data to inform development consent decisions. Here we have evaluated experience related to the assessment programmes at EU wave energy test centres combined with knowledge gained from EIA produced for other similar renewable energy developments. From this we have identified key receptors of concern, as well as the type and magnitude of impacts which may be expected. The key environmental receptors of concern for wave energy EIA include the physical environment (e.g. morphology, waves and current) and flora and fauna(1) as represented by marine mammals, seabirds, benthos, fish and shellfish. From a review of the EIAs performed at wave energy test centres, we identified several lessons regarding the wave energy EIA process. There is clear evidence that the receptors of primary interest are dependent on factors such as the local environmental characteristics, the presence/absence of protected species and the regulatory authority under which the EIA is performed. Furthermore, it is recommended that concerns relating to cumulative impacts, from an expanding level of wave energy development taking place in a background of growing utilisation of the marine environment, which are largely unknown at this early stage of the industry may be comprehensively addressed at the national level as part of a Strategic Environmental Assessment (EIA) and/or in Maritime Spatial Planning (MSP) and that it should be regularly reassessed.
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| 48. |
- Sen, P, et al.
(författare)
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COVID-19 VACCINATION-RELATED ADVERSE EVENTS AMONG AUTOIMMUNE DISEASE PATIENTS: RESULTS FROM THE COVID-19 VACCINATION IN AUTOIMMUNE DISEASES (COVAD) STUDY
- 2022
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Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 81, s. 966-967
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- COVID-19 vaccines have been proven to be safe and effective in the healthy population at large. However, significant gaps remain in the evidence of their safety in patients with systemic autoimmune and inflammatory disorders (SAIDs). Patients and rheumatologists have expressed concerns regarding vaccination triggered allergic reactions, thrombogenic events, and other adverse events (ADEs) contributing to vaccine hesitancy (1)ObjectivesThis study aimed to assess and compare short term COVID-19 vaccination associated ADEs in patients with SAIDs and healthy controls (HC) seven days post-vaccination, as well as between patients with SAIDs receiving different vaccines.MethodsWe developed an comprehensive, patient self-reporting electronic-survey to collect respondent demographics, SAID details, COVID-19 infection history, COVID-19 vaccination details, 7-day post vaccination adverse events and patient reported outcome measures using the PROMIS tool. After pilot testing, validation, translation into 18 languages on the online platform surveymonkey.com, and vetting by international experts, the survey was circulated in early 2021 by a multicenter study group of >110 collaborators in 94 countries. ADEs were categorized as injection site pain, minor ADEs, major ADEs, and hospitalizations. We analyzed data from the baseline survey for descriptive and intergroup comparative statistics based on data distribution and variable type (data as median, IQR).Results10900 respondents [42 (30-55) years, 74% females and 45% Caucasians] were analyzed. 5,867 patients (54%) with SAIDs were compared with 5033 HCs. All respondents included in the final analysis had received a single dose of the vaccine and 69% had received 2 primary doses. Pfizer (39.8%) was the most common vaccine received, followed by Oxford/AstraZeneca (13.4%), and Covishield (10.9%). Baseline demographics differed by an older SAID population (mean age 42 vs. 33 years) and a greater female predominance (M:F= 1:4.7 vs. 1:1.8) compared to HCs.79% had minor and only 3% had major vaccine ADEs requiring urgent medical attention overall. In adjusted analysis, among minor ADEs, abdominal pain [multivariate OR 1.6 (1.14-2.3)], dizziness [multivariate OR 1.3 (1.2-1.5)], and headache [multivariate OR 1.67 (1.3-2.2)], were more frequent in SAIDs than HCs. Overall major ADEs [multivariate OR 1.9 (1.6-2.2)], and throat closure [multivariate OR 5.7 (2.9-11.3)] were more frequent in SAIDs though absolute risk was small (0-4%) and rates of hospitalization were similarly small in both groups, with a small absolute risk (0-4%). Specific minor ADEs frequencies were different among different vaccine types, however, major ADEs and hospitalizations overall were rare (0-4%) and comparable across vaccine types in patients with SAIDs (Figure 1).Figure 1.A. Post Vaccination ADEs in SAIDs compared to HCs. B. Proportions of post COVID-19 vaccination ADEs in SAIDs by vaccine type.ConclusionVaccination against COVID-19 is relatively safe and tolerable in patients with SAIDs. Certain minor vaccine ADEs are more frequent in SAIDs than HCs in this study, though are not severe and do not require urgent medical attention. SAIDs were at a higher risk of major ADEs than HCs, though absolute risk was small, and did not lead to increased hospitalizations. There are small differences in minor ADEs between vaccine types in patients with SAIDs.References[1]Boekel L, Kummer LY, van Dam KPJ, Hooijberg F, van Kempen Z, Vogelzang EH, et al. Adverse events after first COVID-19 vaccination in patients with autoimmune diseases. Lancet Rheumatol. 2021 Aug;3(8):e542–5.AcknowledgementsThe authors thank all members of the COVAD study group for their invaluable role in the collection of data. The authors thank all respondents for filling the questionnaire. The authors thank The Myositis Association, Myositis India, Myositis UK, the Myositis Global Network, Cure JM, Cure IBM, Sjögren’s India Foundation, EULAR PARE, and various other patient support groups and organizations for their invaluable contribution in the dissemination of this survey among patients which made the data collection possible. The authors also thank all members of the COVAD study group.Disclosure of InterestsParikshit Sen: None declared, Naveen R: None declared, Arvind Nune: None declared, James B. Lilleker: None declared, Vishwesh Agarwal: None declared, Sinan Kardes: None declared, Minchul Kim: None declared, Jessica Day Grant/research support from: JD has received research funding from CSL Limited., Marcin Milchert: None declared, Tamer A Gheita: None declared, Babur Salim: None declared, Tsvetelina Velikova: None declared, Abraham Edgar Gracia-Ramos: None declared, Ioannis Parodis Speakers bureau: IP has received research funding and/or honoraria from Amgen, AstraZeneca, Aurinia Pharmaceuticals, Elli Lilly and Company, Gilead Sciences, GlaxoSmithKline, Janssen Pharmaceuticals, Novartis and F. Hoffmann-La Roche AG., Consultant of: IP has received research funding and/or honoraria from Amgen, AstraZeneca, Aurinia Pharmaceuticals, Elli Lilly and Company, Gilead Sciences, GlaxoSmithKline, Janssen Pharmaceuticals, Novartis and F. Hoffmann-La Roche AG., Grant/research support from: IP has received research funding and/or honoraria from Amgen, AstraZeneca, Aurinia Pharmaceuticals, Elli Lilly and Company, Gilead Sciences, GlaxoSmithKline, Janssen Pharmaceuticals, Novartis and F. Hoffmann-La Roche AG., Albert Selva-O’Callaghan: None declared, Elena Nikiphorou Speakers bureau: EN has received speaker honoraria/participated in advisory boards for Celltrion, Pfizer, Sanofi, Gilead, Galapagos, AbbVie, Lilly, Consultant of: EN has received speaker honoraria/participated in advisory boards for Celltrion, Pfizer, Sanofi, Gilead, Galapagos, AbbVie, Lilly, Grant/research support from: EN has received speaker honoraria/participated in advisory boards for Celltrion, Pfizer, Sanofi, Gilead, Galapagos, AbbVie, Lilly, and holds research grants from Pfizer and Lilly., Tulika Chatterjee: None declared, Ai Lyn Tan Speakers bureau: ALT has received honoraria for advisory boards and speaking for Abbvie, Gilead, Janssen, Lilly, Novartis, Pfizer, UCB., Consultant of: ALT has received honoraria for advisory boards and speaking for Abbvie, Gilead, Janssen, Lilly, Novartis, Pfizer, UCB., Grant/research support from: ALT has received honoraria for advisory boards and speaking for Abbvie, Gilead, Janssen, Lilly, Novartis, Pfizer, UCB., Lorenzo Cavagna: None declared, Miguel A Saavedra: None declared, Samuel Katsuyuki Shinjo: None declared, Nelly Ziade Speakers bureau: NZ has received speaker fees, advisory board fees and research grants from Pfizer, Roche, Abbvie, Eli Lilly, NewBridge, Sanofi-Aventis, Boehringer Ingelheim, Janssen, Pierre Fabre; none is related to this manuscript., Consultant of: NZ has received speaker fees, advisory board fees and research grants from Pfizer, Roche, Abbvie, Eli Lilly, NewBridge, Sanofi-Aventis, Boehringer Ingelheim, Janssen, Pierre Fabre; none is related to this manuscript., Grant/research support from: NZ has received speaker fees, advisory board fees and research grants from Pfizer, Roche, Abbvie, Eli Lilly, NewBridge, Sanofi-Aventis, Boehringer Ingelheim, Janssen, Pierre Fabre; none is related to this manuscript., Johannes Knitza: None declared, Masataka Kuwana: None declared, Oliver Distler Speakers bureau: OD has/had consultancy relationship with and/or has received research funding from or has served as a speaker for the following companies in the area of potential treatments for systemic sclerosis and its complications in the last three years: Abbvie, Acceleron, Alcimed, Amgen, AnaMar, Arxx, Baecon, Blade, Bayer, Boehringer Ingelheim, ChemomAb, Corbus, CSL Behring, Galapagos, Glenmark, GSK, Horizon (Curzion), Inventiva, iQvia, Kymera, Lupin, Medac, Medscape, Mitsubishi Tanabe, Novartis, Roche, Roivant, Sanofi, Serodapharm, Topadur and UCB. Patent issued “mir-29 for the treatment of systemic sclerosis” (US8247389, EP2331143)., Consultant of: OD has/had consultancy relationship with and/or has received research funding from or has served as a speaker for the following companies in the area of potential treatments for systemic sclerosis and its complications in the last three years: Abbvie, Acceleron, Alcimed, Amgen, AnaMar, Arxx, Baecon, Blade, Bayer, Boehringer Ingelheim, ChemomAb, Corbus, CSL Behring, Galapagos, Glenmark, GSK, Horizon (Curzion), Inventiva, iQvia, Kymera, Lupin, Medac, Medscape, Mitsubishi Tanabe, Novartis, Roche, Roivant, Sanofi, Serodapharm, Topadur and UCB. Patent issued “mir-29 for the treatment of systemic sclerosis” (US8247389, EP2331143)., Grant/research support from: OD has/had consultancy relationship with and/or has received research funding from or has served as a speaker for the following companies in the area of potential treatments for systemic sclerosis and its complications in the last three years: Abbvie, Acceleron, Alcimed, Amgen, AnaMar, Arxx, Baecon, Blade, Bayer, Boehringer Ingelheim, ChemomAb, Corbus, CSL Behring, Galapagos, Glenmark, GSK, Horizon (Curzion), Inventiva, iQvia, Kymera, Lupin, Medac, Medscape, Mitsubishi Tanabe, Novartis, Roche, Roivant, Sanofi, Serodapharm, Topadur and UCB. Patent issued “mir-29 for the treatment of systemic sclerosis” (US8247389, EP2331143)., Hector Chinoy Speakers bureau: HC has served as a speaker for UCB, Biogen., Consultant of: HC has received consulting fees from Novartis, Eli Lilly, Orphazyme, Astra Zeneca, Grant/research support from: HC has received grant support from Eli Lilly and UCB, Vikas Agarwal: None declared, Rohit Aggarwal Consultant of: RA has/had a consultancy relationship with and/or has received research funding from for the following companies-Bristol Myers-Squibb, Pfizer, Genentech, Octapharma, CSL Behring, Mallinckrodt, AstraZeneca, Corbus, Kezar, Kyverna, Janssen, Roivant, Boehringer Ingelheim, Argenx, Q32, Alexion, EMD S
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| 49. |
- Yoshida, A, et al.
(författare)
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IMPAIRED PROMIS PHYSICAL FUNCTION IN IDIOPATHIC INFLAMMATORY MYOPATHY PATIENTS: RESULTS FROM THE MULTICENTER COVAD PATIENT REPORTED E-SURVEY
- 2022
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Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 81, s. 720-722
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Evaluation of physical function is fundamental in the management of idiopathic inflammatory myopathies (IIMs). Patient-Reported Outcome Measurement Information System (PROMIS) is a National Institute of Health initiative established in 2004 to develop patient-reported outcome measures (PROMs) with improved validity and efficacy. PROMIS Physical Function (PF) short forms have been validated for use in IIMs [1].ObjectivesTo investigate the physical function status of IIM patients compared to those with non-IIM autoimmune diseases (AIDs) and healthy controls (HCs) utilizing PROMIS PF data obtained in the coronavirus disease-2019 (COVID-19) Vaccination in Autoimmune Diseases (COVAD) study, a large-scale, international self-reported e-survey assessing the safety of COVID-19 vaccines in AID patients [2].MethodsThe survey data regarding demographics, IIM and AID diagnosis, disease activity, and PROMIS PF short form-10a scores were extracted from the COVAD study database. The disease activity (active vs inactive) of each patient was assessed in 3 different ways: (1) physician’s assessment (active if there was an increased immunosuppression), (2) patient’s assessment (active vs inactive as per patient), and (3) current steroid use. These 3 definitions of disease activity were applied independently to each patient. PROMIS PF-10a scores were compared between each disease category (IIMs vs non-IIM AIDs vs HCs), stratified by disease activity based on the 3 definitions stated above, employing negative binominal regression model. Multivariable regression analysis adjusted for age, gender, and ethnicity was performed clustering countries, and the predicted PROMIS PF-10a score was calculated based on the regression result. Factors affecting PROMIS PF-10a scores other than disease activity were identified by another multivariable regression analysis in the patients with inactive disease (IIMs or non-IIM AIDs).Results1057 IIM patients, 3635 non-IIM AID patients, and 3981 HCs responded to the COVAD survey until August 2021. The median age of the respondents was 43 [IQR 30-56] years old, and 74.8% were female. Among IIM patients, dermatomyositis was the most prevalent diagnosis (34.8%), followed by inclusion body myositis (IBM) (23.6%), polymyositis (PM) (16.2%), anti-synthetase syndrome (11.8%), overlap myositis (7.9%), and immune-mediated necrotizing myopathy (IMNM) (4.6%). The predicted mean of PROMIS PF-10a scores was significantly lower in IIMs compared to non-IIM AIDs or HCs (36.3 [95% (CI) 35.5-37.1] vs 41.3 [95% CI 40.2-42.5] vs 46.2 [95% CI 45.8-46.6], P < 0.001), irrespective of disease activity or the definitions of disease activity used (physician’s assessment, patient’s assessment, or steroid use) (Figure 1). The largest difference between active IIMs and non-IIM AIDs was observed when the disease activity was defined by patient’s assessment (35.0 [95% CI 34.1-35.9] vs 40.1 [95% CI 38.7-41.5]). Considering the subgroups of IIMs, the scores were significantly lower in IBM in comparison with non-IBM IIMs (P < 0.001). The independent factors associated with low PROMIS PF-10a scores in the patients with inactive disease were older age, female gender, and the disease category being IBM, PM, or IMNM.ConclusionPhysical function is significantly impaired in IIMs compared to non-IIM AIDs or HCs, even in patients with inactive disease. The elderly, women, and IBM groups are the worst affected, suggesting that developing targeted strategies to minimize functional disability in certain groups may improve patient reported physical function and disease outcomes.References[1]Saygin D, Oddis CV, Dzanko S, et al. Utility of patient-reported outcomes measurement information system (PROMIS) physical function form in inflammatory myopathy. Semin Arthritis Rheum. 2021; 51: 539-46.[2]Sen P, Gupta L, Lilleker JB, et al. COVID-19 vaccination in autoimmune disease (COVAD) survey protocol. Rheumatol Int. 2022; 42: 23-9.AcknowledgementsThe authors thank all respondents for filling the questionnaire. The authors thank The Myositis Association, Myositis India, Myositis UK, the Myositis Global Network, Cure JM, Cure IBM, Sjögren’s India Foundation, EULAR PARE, and various other patient support groups and organizations for their invaluable contribution in the dissemination of this survey among patients which made the data collection possible. The authors also thank all members of the COVAD study group.Disclosure of InterestsNone declared
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