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  • Khatri, B., et al. (författare)
  • Genome-wide association study identifies Sjogren's risk loci with functional implications in immune and glandular cells
  • 2022
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Sjogren's disease is a complex autoimmune disease with twelve established susceptibility loci. This genome-wide association study (GWAS) identifies ten novel genome-wide significant (GWS) regions in Sjogren's cases of European ancestry: CD247, NAB1, PTTG1-MIR146A, PRDM1-ATG5, TNFAIP3, XKR6, MAPT-CRHR1, RPTOR-CHMP6-BAIAP6, TYK2, SYNGR1. Polygenic risk scores yield predictability (AUROC = 0.71) and relative risk of 12.08. Interrogation of bioinformatics databases refine the associations, define local regulatory networks of GWS SNPs from the 95% credible set, and expand the implicated gene list to >40. Many GWS SNPs are eQTLs for genes within topologically associated domains in immune cells and/or eQTLs in the main target tissue, salivary glands. The genetic architecture underlying Sjogren's syndrome is not fully understood. Here, the authors perform a genome-wide association study to identify 10 new genetic risk regions, implicating genes involved in immune and salivary gland function.
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  • Salomonsson, S., et al. (författare)
  • A Population-based Investigation of the Autoantibody Profile in Mothers of Children with Atrioventricular Block
  • 2011
  • Ingår i: Scandinavian Journal of Immunology. - Oxford : Blackwell Publishing. - 0300-9475 .- 1365-3083. ; 74:5, s. 511-517
  • Tidskriftsartikel (refereegranskat)abstract
    • The objective of the study was to investigate the antigen specificity and occurrence of individual autoantibodies in mothers of children diagnosed with atrioventricular (AV) block in a nation-wide setting. Patients with AV block detected before 15 years of age were identified using national quality registries as well as a network of pediatric and adult cardiologists and rheumatologists at the six university hospitals in Sweden. Patients with gross heart malformations, surgically or infectiously induced blocks were excluded. Blood samples were obtained from the mothers and maternal autoantibody profile, including the occurrence of antibodies against Ro52, Ro60, La, SmB, SmD, RNP-70k, RNP-A, RNP-C, CENP-C, Scl-70, Jo-1, ribosomal RNP and histones was investigated in 193 mothers of children with AV block by immunoblotting and ELISA. Autoantibody reactivity was detected in 48% (93/193) of the mothers of children with AV block. In autoantibody-positive mothers, the vast majority, 95% (88/93), had antibodies against Ro52, while 63% (59/93) had autoantibodies to Ro60 and 58% (54/93) had autoantibodies to La. In addition, 13% (12/93) of the autoantibody-positive mothers had antibodies to other investigated antigens besides Ro52, Ro60 and La, and of these anti-histone antibodies were most commonly represented, detected in 8% (7/93) of the mothers. In conclusion, this Swedish population-based study confirms that maternal autoantibodies may associate with heart block in the child. Further, our data demonstrate a dominant role of Ro52 antibodies in association with AV block.
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  • Amkreutz, J. A. M. P., et al. (författare)
  • Association Between Bone Mineral Density and Autoantibodies in Patients With Rheumatoid Arthritis
  • 2021
  • Ingår i: Arthritis and Rheumatology. - : Wiley. - 2326-5191 .- 2326-5205. ; 73:6, s. 921-930
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Autoantibodies, such as anti–citrullinated protein antibodies (ACPAs), have been described as inducing bone loss in rheumatoid arthritis (RA), which can also be reflected by bone mineral density (BMD). We therefore examined the association between osteoporosis and autoantibodies in two independent RA cohorts. Methods: Dual x-ray absorptiometry (DXA) of the lumbar spine and left hip was performed in 408 Dutch patients with early RA during 5 years of follow-up and in 198 Swedish patients with early RA during 10 years of follow-up. The longitudinal effect of ACPAs and other autoantibodies on several BMD measures was assessed using generalized estimating equations. Results: In the Dutch cohort, significantly lower BMD at baseline was observed in ACPA-positive patients compared to ACPA-negative patients, with an estimated marginal mean BMD in the left hip of 0.92 g/cm2 (95% confidence interval [95% CI] 0.91–0.93) versus 0.95 g/cm2 (95% CI 0.93–0.97) (P = 0.01). In line with this, significantly lower Z scores at baseline were noted in the ACPA-positive group compared to the ACPA-negative group (estimated marginal mean Z score in the left hip of 0.18 [95% CI 0.08–0.29] versus 0.48 [95% CI 0.33–0.63]) (P < 0.01). However, despite clear differences at baseline, ACPA positivity was not associated with greater decrease in absolute BMD or Z scores over time. Furthermore, there was no association between BMD and higher levels of ACPAs or other autoantibodies (rheumatoid factor and anti–carbamylated protein antibodies). In the Swedish cohort, ACPA-positive patients tended to have a higher prevalence of osteopenia at baseline (P = 0.04), but again, ACPA positivity was not associated with an increased prevalence of osteopenia or osteoporosis over time. Conclusion: The presence of ACPAs is associated with significantly lower BMD at baseline, but not with greater BMD loss over time in treated RA patients. These results suggest that ACPAs alone do not appear to contribute to bone loss after disease onset when disease activity is well-managed. © 2020 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.
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  • Geale, Kirk, et al. (författare)
  • Persistence of biologic treatment in psoriatic arthritis : a population-based study in Sweden
  • 2020
  • Ingår i: Annals of the Rheumatic Diseases. - : BMJ Publishing Group Ltd. - 0003-4967 .- 1468-2060. ; 79, s. 37-38
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Psoriatic arthritis (PsA) is a chronic, heterogeneous, immune-mediated seronegative arthritis characterized by joint inflammation in people with skin psoriasis (PsO). In recent years several effective biologic treatments such as tumour necrosis factor inhibitors (TNFi), interleukin (IL) 12 and 23 inhibitors (IL-12/23i), and IL 17 inhibitors (IL-17i) have been introduced for PsA. Discontinuation (non-persistence) of therapy is usually a consequence of lack of effect and intolerability.Objectives:Compare time to discontinuation of TNFi (adalimumab, ADA), IL-17i (secukinumab, SEC), and IL-12/23i (ustekinumab, UST) treatment exposures and the association with previous biologic treatment experience.Methods:Population-based national health data from the Swedish Patient Registry, Prescribed Drug Registry and Cause of Death Registry were linked at the patient level and used to identify treatment exposures in PsA patients initiating ADA, SEC, or UST between January 2008 and September 2018. Discontinuation was defined as a treatment switch to any other PsA-indicated biologic, or failure to re-dispense treatment within a grace period following end of drug supplied. The grace period, defined as the number of days between end of drug supply and re-dispensation during which a patient is considered to be on active treatment, was set dynamically to the number of days of drug supplied in the primary analysis. As a sensitivity analysis, a fixed 90-day grace period was used. Supply was calculated as total milligrams dispensed divided by maintenance dose posology, where the following assumptions were made due to the limitations of the administrative data used: UST patients’ weight corresponded to the amount of drug dispensed (both 45mg and 90mg dispensations last 84 days), SEC patients with prior TNFi experience consumed 300mg/28 days and all others consumed 150mg/28 days, and ADA patients consumed 40mg/14 days. Adjusted hazard ratios (HR) for time to discontinuation were calculated using a Cox proportional hazards model. Covariates for age, marital status, and previous biologic treatment experience were assessed at the initiation of treatment exposure, while comorbidity including skin PsO was assessed during the two years prior. Exposures without discontinuation events were censored at death or end of follow-up. The study was approved by the Stockholm Regional Ethical Review Board.Results:3,620 discontinuation events were observed in the main analysis across 4,649 treatment exposures (ADA: 3,255; SEC: 887; UST: 507) (Figure 1, unadjusted). 3,162 events were observed in the sensitivity analysis. Average age at treatment initiation was 50, 54% were female, 47% were biologic treatment naïve, and 39% had skin PsO. In the multivariate main analysis, UST exhibited lower discontinuation rates vs ADA (HR=0.56, 95% CI: 0.49-0.64) while there was no significant difference between SEC and ADA (HR=1.01, 95% CI: 0.88-1.15). In the multivariate sensitivity analysis, both UST (HR=0.81, 95% CI: 0.70-0.94) and SEC (HR=0.82, 95% CI: 0.70-0.95) were associated with significantly lower discontinuation rates ratio relative to ADA. Overall, patients with more biologic treatment experience were statistically significantly (p<0.05) associated with higher risk of treatment discontinuation.Figure 1.Unadjusted Kaplan-Meier curves of time to treatment discontinuation (main analysis, dynamic grace period)Conclusion:UST exhibits a favourable treatment persistency profile relative to ADA, regardless of the grace period definition. The relative risk of discontinuing SEC vs ADA is sensitive to the grace period. Treatment discontinuation was higher in treatment exposures with more biologic experience.Disclosure of Interests:Kirk Geale Consultant of: Quantify Research, Speakers bureau: Indirectly as a consultant, Ingrid Lindberg Consultant of: Quantify Research, Emma Paulsson Consultant of: Quantify Research, Christina Wennerström Employee of: Janssen-Cilag Sweden AB, Anna Tjärnlund Employee of: Janssen-Cilag Sweden AB, Virginia Taliadouros Shareholder of: JnJ, Employee of: Janssen Pharmaceuticals NV, Wim Noel Employee of: Janssen Pharmaceuticals NV, Dana Enkusson Employee of: Janssen-Cilag AB, Elke Theander Employee of: Janssen-Cilag Sweden AB, Sara Bruce Wirta Employee of: Janssen-Cilag Sweden AB
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  • Sena, AG, et al. (författare)
  • FIRST LINE TREATMENT WITH CONVENTIONAL SYNTHETIC DISEASE MODIFYING ANTIRHEUMATIC DRUGS IN RHEUMATOID ARTHRITIS: A MULTINATIONAL POPULATION-BASED COHORT FROM 14 REAL WORLD HEALTHCARE DATABASES AND 9 COUNTRIES - REALITY VERSUS GUIDELINES
  • 2020
  • Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 79, s. 327-327
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • Treatment guidelines recommend early initiation of csDMARDs following diagnosis of rheumatoid arthritis (RA), with methotrexate (MTX) as first-line therapy. Scarce evidence exists on adherence to this guidanceObjectives:To characterize first-line csDMARD treatment during the first year following an RA diagnosis.Methods:14 real world databases (3 Primary care, 6 primary/secondary care records, 5 claims) from 9 countries were included, all mapped to the OMOP common data model.Patients were included on the earliest event of: 1st diagnosis of RA or 1st DMARD prescription with an RA diagnosis within 30 days. Patients were >18 years-old, required 1+ year pre-index data, and at least 1-year follow-up. Study period covered 2000-2018. Previous users of DMARDs or non-RA inflammatory arthritis history were excluded. Only MTX, Hydroxychloroquine (HCQ), Sulfasalazine (SSZ) and Leflunomide (LEF) were available in all databases.Results:We identified 323,547 eligible participants. Large variation was observed internationally (Figure 1). MTX as first-line monotherapy ranged from 33.3% to 74.5%, and in combination with HCQ from 2.1% to 6.7%. Three additional csDMARDs were used as first-line: HCQ in 10.1% to 30.2%, SSZ in 0.9% to 28.7%, and LEF in 1.8% to 15.2%.Figure 1.First line csDMARD treatment during 1yr from first observed RA diagnosisConclusion:We report wide heterogeneity of first-line csDMARDs regimens internationally. Despite recommendations for MTX to be first line therapy, data suggest that a large proportion of patients receive alternative csDMARD.Disclosure of Interests: :Anthony G Sena Shareholder of: J&J shares, Grant/research support from: Full-time employment salary from Janssen, Consultant of: Full-time employment salary from Janssen, Employee of: Janssen employee, Paid instructor for: Janssen employee, Speakers bureau: Janssen employee, Denis Granados: None declared, Nigel Hughes Shareholder of: J&J shares, Grant/research support from: Full-time employment salary from Janssen, Consultant of: Janssen employee, Employee of: Janssen employee, Paid instructor for: Janssen employee, Speakers bureau: Janssen employee, WALID FAKHOURI Shareholder of: E Lilly Shares, Employee of: Eli Lilly and Company, Antje Hottgenroth Shareholder of: Eli Lilly shares, Employee of: Lilly Deutschland GmbH, Raivo Kolde: None declared, Sulev Reisberg: None declared, Carmen Olga Torre: None declared, Talita Duarte-Salles: None declared, Yesika Díaz: None declared, Jose Felipe Golib-Dzib Grant/research support from: Full-time employment salary from Janssen, Employee of: Yes, Janssen employee, Paid instructor for: Janssen Employee, Speakers bureau: Janssen Employee, Emily S. Brouwer Shareholder of: J&J shares, Takeda shares, Grant/research support from: Full-time employment salary from Janssen, Consultant of: Janssen employee, Employee of: Janssen employee, Paid instructor for: Janssen Employee, Speakers bureau: Janssen Employee, Edward Burn: None declared, Jennifer Lane: None declared, David Vizcaya Employee of: Bayer, Sara Bruce Wirta Employee of: Janssen-Cilag Sweden AB, Marcel de Wilde: None declared, Katia Verhamme: None declared, Peter Rijnbeek: None declared, Elke Theander Employee of: Janssen-Cilag Sweden AB, Katerina Chatzidionysiou Consultant of: AbbVie, Pfizer, Lilly., Daniel Prieto-Alhambra Grant/research support from: Professor Prieto-Alhambra has received research Grants from AMGEN, UCB Biopharma and Les Laboratoires Servier, Consultant of: DPA’s department has received fees for consultancy services from UCB Biopharma, Speakers bureau: DPA’s department has received fees for speaker and advisory board membership services from Amgen, Patrick Ryan: None declared
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  • Theander, E, et al. (författare)
  • Activities of daily living decrease similarly in hospital-treated patients with a hip fracture or a vertebral fracture: a one-year prospective study in 151 patients
  • 2004
  • Ingår i: Scandinavian Journal of Public Health. - : SAGE Publications. - 1651-1905 .- 1403-4948. ; 32:5, s. 356-360
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims: A hip fracture is commonly regarded as the most devastating fragility fracture, as regards both morbidity and mortality, while a vertebral fracture is usually regarded as having lower general morbidity. The purpose of this study was to investigate whether hospitalized patients with a hip or a vertebral fracture experience similar functional deterioration following the fracture as regards activity of daily living (ADL) and experienced quality of life (QOL). Methods: Eighty-seven women and 22 men, mean age 81 (range 66-96), with a hip fracture and 34 women and 8 men, mean age 81 (range 68-92), with a vertebral fracture were followed up for 12 months. ADL before fracture and at 4 and 12 months after the fracture were evaluated as well as QOL at 4 and 12 months after the fracture, by questionnaires. Results: A hip and a vertebral fracture in community dwellers within the same age range confers a similar decrease in ADL during the four months following the fracture. No restoration was seen in ADL or total QOL during the year following the fracture. Patients with a vertebral fracture had a lower QOL than patients with a hip fracture 4 and 12 months after the fracture. Conclusion: The need for external community assistance for patients with a vertebral fracture that forces them to have hospital treatment may be similar to the need following a hip fracture.
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  • Vasaitis, Lilian, et al. (författare)
  • Comparison of patients with and without pre-existing lymphoma at diagnosis of primary Sjögren's syndrome
  • 2019
  • Ingår i: Scandinavian Journal of Rheumatology. - : Informa UK Limited. - 0300-9742 .- 1502-7732. ; 48:3, s. 207-212
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: In the 2016 American College of Rheumatology/European League Against Rheumatism classification criteria for primary Sjögren's syndrome (pSS), pre-existing lymphoma is not an exclusion criterion for pSS diagnosis, as in earlier criteria. We aimed to explore whether there are differences between pSS patients with and without pre-existing lymphoma at pSS diagnosis.METHOD: Patients with ICD-7-10 codes for Sjögren's syndrome (SS) and a diagnosis of malignant lymphoma before or after SS diagnosis were identified by linking the Swedish Patient Register 1964-2007 with the Cancer Register 1990-2007 (n = 224). Clinical data were collected from medical records. Lymphoma diagnoses were evaluated by tissue review. Characteristics of pSS patients with and without pre-existing lymphoma were compared.RESULTS: We identified 107 patients with pSS as the reason for an SS diagnosis code and a verified lymphoma. Of these, 18 (17%) had a pre-existing lymphoma at pSS diagnosis, defined as lymphoma diagnosed before or within 6 months of pSS diagnosis. Male gender (39% vs 10%, p = 0.006), enlarged lymph nodes during the pSS disease (61% vs 27%, p = 0.01), mucosa-associated lymphoid tissue (MALT) lymphoma (50% vs 22%, p = 0.02), and salivary gland lymphoma (61% vs 26%, p = 0.006) were more common in patients with a pre-existing lymphoma at pSS diagnosis. Other pSS characteristics were similar.CONCLUSION: In a substantial proportion of patients, particularly in men, pSS remains undiagnosed until after lymphoma diagnosis. The study highlights the importance of pSS investigation in patients with lymphoma, especially MALT lymphoma, in the salivary glands.
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  • Vasaitis, Lilian, et al. (författare)
  • Population-based study of patients with primary Sjögren’s syndrome and lymphoma : lymphoma subtypes, clinical characteristics, and gender differences
  • 2020
  • Ingår i: Scandinavian Journal of Rheumatology. - : Informa UK Limited. - 0300-9742 .- 1502-7732. ; 49:3, s. 225-232
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To examine lymphoma subtypes, clinical characteristics, and gender differences in patients with primary Sjögren’s syndrome (pSS) and lymphoma in a population-based setting. Method: Patients with Sjögren’s syndrome and lymphoma diagnoses were identified by linkage of the Swedish Patient Register 1964–2007 with the Cancer Register 1990–2007. Clinical data were collected from medical records and lymphoma tissues were re-examined. The lymphoma subtype distribution was compared with the Swedish Lymphoma Register. Results: We identified 105 pSS patients with lymphoma. Diffuse large B-cell lymphoma (DLBCL) (32%) and marginal zone lymphoma [MZL including mucosa-associated lymphoid tissue (MALT) lymphoma] (31%) were the most common lymphoma subtypes. The proportion of DLBCL was not increased compared to the general population reference (32%, p = 1), in contrast to MZL (general population 5%, p < 0.0001). Compared to DLBCL, MALT lymphoma was diagnosed at a younger age (55 vs 67 years, p = 0.0001), and earlier after patient-reported sicca onset (7 vs 18 years, p = 0.0001) and pSS diagnosis (2 vs 9 years, p = 0.0005). Sixteen of the pSS-lymphoma cases were men (15%), twice the proportion in general pSS populations. Compared to women, men had a shorter median time from pSS diagnosis to lymphoma diagnosis (1 vs 8 years, p = 0.0003) and more often had lymphoma in the salivary glands (56% vs 29%, p = 0.04). Conclusion: DLBCL and MZL are common in pSS patients, but only MZL/MALT lymphoma occurs at an increased relative frequency in pSS compared to the general population. The study supports increased awareness of signs of lymphoma in men in the first years after pSS diagnosis.
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  • Ayres Pereira, Marina, et al. (författare)
  • Placental Sequestration of Plasmodium falciparum Malaria Parasites Is Mediated by the Interaction Between VAR2CSA and Chondroitin Sulfate A on Syndecan-1
  • 2016
  • Ingår i: PLoS Pathogens. - : Public Library of Science (PLoS). - 1553-7366 .- 1553-7374. ; 12:8
  • Tidskriftsartikel (refereegranskat)abstract
    • During placental malaria, Plasmodium falciparum infected erythrocytes sequester in the placenta, causing health problems for both the mother and fetus. The specific adherence is mediated by the VAR2CSA protein, which binds to placental chondroitin sulfate (CS) on chondroitin sulfate proteoglycans (CSPGs) in the placental syncytium. However, the identity of the CSPG core protein and the cellular impact of the interaction have remain elusive. In this study we identified the specific CSPG core protein to which the CS is attached, and characterized its exact placental location. VAR2CSA pull-down experiments using placental extracts from whole placenta or syncytiotrophoblast microvillous cell membranes showed three distinct CSPGs available for VAR2CSA adherence. Further examination of these three CSPGs by immunofluorescence and proximity ligation assays showed that syndecan-1 is the main receptor for VAR2CSA mediated placental adherence. We further show that the commonly used placental choriocarcinoma cell line, BeWo, express a different set of proteoglycans than those present on placental syncytiotrophoblast and may not be the most biologically relevant model to study placental malaria. Syncytial fusion of the BeWo cells, triggered by forskolin treatment, caused an increased expression of placental CS-modified syndecan-1. In line with this, we show that rVAR2 binding to placental CS impairs syndecan-1-related Src signaling in forskolin treated BeWo cells, but not in untreated cells.
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  • Brito-Zerón, Pilar, et al. (författare)
  • Influence of geolocation and ethnicity on the phenotypic expression of primary Sjögren's syndrome at diagnosis in 8310 patients : a cross-sectional study from the Big Data Sjögren Project Consortium
  • 2017
  • Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 76:6, s. 1042-1050
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: To analyse the influence of geolocation and ethnicity on the clinical presentation of primary Sjögren's syndrome (SjS) at diagnosis.METHODS: The Big Data Sjögren Project Consortium is an international, multicentre registry designed in 2014. By January 2016, 20 centres from five continents were participating. Multivariable logistic regression analyses were performed.RESULTS: We included 7748 women (93%) and 562 men (7%), with a mean age at diagnosis of primary SjS of 53 years. Ethnicity data were available for 7884 patients (95%): 6174 patients (78%) were white, 1066 patients (14%) were Asian, 393 patients (5%) were Hispanic, 104 patients (1%) were black/African-American and 147 patients (2%) were of other ethnicities. SjS was diagnosed a mean of 7 years earlier in black/African-American compared with white patients; the female-to-male ratio was highest in Asian patients (27:1) and lowest in black/African-American patients (7:1); the prevalence of sicca symptoms was lowest in Asian patients; a higher frequency of positive salivary biopsy was found in Hispanic and white patients. A north-south gradient was found with respect to a lower frequency of ocular involvement in northern countries for dry eyes and abnormal ocular tests in Europe (OR 0.46 and 0.44, respectively) and Asia (OR 0.18 and 0.49, respectively) compared with southern countries. Higher frequencies of antinuclear antibodies (ANAs) were reported in northern countries in America (OR=1.48) and Asia (OR=3.80) while, in Europe, northern countries had lowest frequencies of ANAs (OR=0.67) and Ro/La (OR=0.69).CONCLUSIONS: This study provides the first evidence of a strong influence of geolocation and ethnicity on the phenotype of primary SjS at diagnosis.
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  • Gardulf, A., et al. (författare)
  • The Nurse Professional Competence (NPC) Scale: Self-reported competence among nursing students on the point of graduation
  • 2016
  • Ingår i: Nurse Education Today. - : Elsevier BV. - 0260-6917 .- 1532-2793. ; 36, s. 165-171
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: International organisations, e.g. WHO, stress the importance of competent registered nurses (RN) for the safety and quality of healthcare systems. Low competence among RNs has been shown to increase the morbidity and mortality of inpatients. Objectives: To investigate self-reported competence among nursing students on the point of graduation (NSPGs), using the Nurse Professional Competence (NPC) Scale, and to relate the findings to background factors. Methods and participants; The NPC Scale consists of 88 items within eight competence areas (CAs) and two overarching themes. Questions about socio-economic background and perceived overall quality of the degree programme were added. In total, 1086 NSPGs (mean age, 28.1[20-56] years, 87.3% women) from 11 universities/university colleges participated. Results: NSPGs reported significantly higher scores for Theme I "Patient-Related Nursing" than for Theme II "Organisation and Development of Nursing Care". Younger NSPGs (20-27 years) reported significantly higher scores for the CAs "Medical and Technical Care" and "Documentation and Information Technology". Female NSPGs scored significantly higher for "Value-Based Nursing". Those who had taken the nursing care programme at upper secondary school before the Bachelor of Science in Nursing (BSN) programme scored significantly higher on "Nursing Care", "Medical and Technical Care", "Teaching/Learning and Support", "Legislation in Nursing and Safety Planning" and on Theme I. Working extra paid hours in healthcare alongside the BSN programme contributed to significantly higher self-reported scores for four CAs and both themes. Clinical courses within the BSN programme contributed to perceived competence to a significantly higher degree than theoretical courses (932% vs 875% of NSPGs). Summary and conclusion: Mean scores reported by NSPGs were highest for the four CAs connected with patient-related nursing and lowest for CAs relating to organisation and development of nursing care. We conclude that the NPC Scale can be used to identify and measure aspects of self-reported competence among NSPGs. (C) 2015 Elsevier Ltd. All rights reserved.
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  • Geale, Kirk, et al. (författare)
  • Persistence of biologic treatments in psoriatic arthritis : a population-based study in Sweden
  • 2020
  • Ingår i: Rheumatology. - : Oxford University Press. - 2514-1775. ; 4:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: TNF inhibitors (TNFis) and IL inhibitors are effective treatments for PsA. Treatment non-persistence (drug survival, discontinuation) is a measure of effectiveness, tolerability and patient satisfaction or preferences in real-world clinical practice. Persistence on these treatments is not well understood in European PsA populations. The aim of this study was to compare time to non-persistence for either ustekinumab (IL-12/23 inhibitor) or secukinumab (IL-17 inhibitor) to a reference group of adalimumab (TNFi) treatment exposures in PsA patients and identify risk factors for non-persistence.Methods: A total of 4649 exposures of adalimumab, ustekinumab, and secukinumab in 3918 PsA patients were identified in Swedish longitudinal population-based registry data. Kaplan-Meier curves were constructed to measure treatment-specific real-world risk of non-persistence and adjusted Cox proportional hazards models were estimated to identify risk factors associated with non-persistence.Results: Ustekinumab was associated with a lower risk of non-persistence relative to adalimumab in biologic-naive [hazard ratio (HR) 0.48 (95% CI 0.33, 0.69)] and biologic-experienced patients [HR 0.65 (95% CI 0.56, 0.76)], while secukinumab was associated with a lower risk in biologic-naive patients [HR 0.65 (95% CI 0.49, 0.86)] but a higher risk of non-persistence in biologic-experienced patients [HR 1.20 (95% CI 1.03, 1.40)]. Biologic non-persistence was also associated with female sex, axial involvement, recent disease onset, biologic treatment experience and no psoriasis.Conclusion: Ustekinumab exhibits a favourable treatment persistency profile relative to adalimumab overall and across lines of treatment. The performance of secukinumab is dependent on biologic experience. Persistence and risk factors for non-persistence should be accounted for when determining an optimal treatment plan for patients.
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  • Gillissen, S, et al. (författare)
  • Synthesis and characterization of poly(pyridine vinylene) via the sulfinyl precursor route
  • 2001
  • Ingår i: Macromolecules. - : American Chemical Society (ACS). - 0024-9297 .- 1520-5835. ; 34:21, s. 7294-7299
  • Tidskriftsartikel (refereegranskat)abstract
    • The synthesis and characterization of poly(pyridine vinylene) (PPyV) via the nonionic sulfinyl precursor route is presented. Starting from an unsymmetrical monomer, precursor polymers were prepared in various solvents, which led to polymers with variable molecular weights. The thermal conversion to the conjugated structure, as well as its stability, was studied with different techniques such as FT-IR, UV-vis, TGA, and direct insertion probe mass spectroscopy (DIP-MS). From these results we were able to derive the most suitable conditions to perform the conversion. The fully conjugated PPyV was further characterized with photoluminescence (PL) and cyclic voltammetry (CV) measurements. The PL efficiency was found to be as high as 14%. The CV measurements showed that the polymer can be reduced (n-doped).
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  • Keil, M, et al. (författare)
  • Process development and characterization of antisticking layers on nickel-based stamps designed for nanoimprint lithography
  • 2004
  • Ingår i: Journal of Vacuum Science and Technology B. - : American Vacuum Society. - 1520-8567. ; 22:6, s. 3283-3287
  • Tidskriftsartikel (refereegranskat)abstract
    • Thin films of different derivatives of fluorinated alkyl phosphoric acids have been deposited from aqueous solutions onto surfaces of oxidized polycrystalline nickel stamps. which are commonly used in several industrial applications of nanoimprint lithography (NIL). The films have been established in order to increase the antiadhesion tendencies at the stamp polymer interface. Thicknesses, chemical compositions, and purities of the films as well as binding mechanisms to the stamp surfaces have been determined by photoelectron spectroscopy (XPS). The results demonstrate the adsorption of highly pure films having thicknesses in the monomolecular region, whose chemical compositions are characterized by large ratios of fluorinated to nonfluorinated carbon species. The high ionic nature of Ni-oxide benefits strong ionic linkages between the phosphate groups of the fluorinated antisticking film and the stamp surface, allowing a large-scale production of imprints with patterned stamps having feature sizes down to 100 nm. (C) 2004 American Vacuum Society.
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41.
  • Nilsson, Jan, et al. (författare)
  • Disaster nursing: Self-reported competence of nursing students and registered nurses, with focus on their readiness to manage violence, serious events and disasters
  • 2016
  • Ingår i: Nurse Education in Practice. - : Elsevier BV. - 1471-5953 .- 1873-5223. ; 17, s. 102-108
  • Tidskriftsartikel (refereegranskat)abstract
    • The World Health Organization and the International Council of Nurses recognises the importance of nurses' involvement in disaster preparedness and response. The aim of this study was to describe and compare self reported disaster nursing competence (DNC) among nursing students (NSs) and among registered nurses (RNs) with professional experience. Further to investigate possible associations between self-reported DNC and background factors. A cross-sectional study was conducted of 569 NSs and 227 RNs. All respondents completed the 88-item Nurse Professional Competence Scale, including three items assessing DNC. Significant differences were found among the NSs depending on which University/University College they had attended. RNs reported significantly higher overall DNC and better ability to handle situations involving violence, and to apply principles of disaster medicine during serious events. RNs working in emergency care reported significantly better DNC ability, compared with RNs working in other areas of healthcare. Multiple linear regression analysis showed that working night shift and working in emergency care were positively associated with high self-reported overall DNC. The results indicate that workplace experience of serious events increase the readiness of registered nurses to handle violence, to act in accordance with safety regulations, and to apply principles of disaster medicine during serious events. (C) 2015 Elsevier Ltd. All rights reserved.
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45.
  • Nordmark, Gunnel, et al. (författare)
  • Association of EBF1, FAM167A(C8orf13)-BLK and TNFSF4 gene variants with primary Sjögren's syndrome
  • 2011
  • Ingår i: Genes and Immunity. - : Springer Science and Business Media LLC. - 1466-4879 .- 1476-5470. ; 12:2, s. 100-109
  • Tidskriftsartikel (refereegranskat)abstract
    • We performed a candidate gene association study in 540 patients with primary Sjögren's Syndrome (SS) from Sweden (n=344) and Norway (n=196) and 532 controls (n=319 Swedish, n=213 Norwegian). A total of 1139 single-nucleotide polymorphisms (SNPs) in 84 genes were analyzed. In the meta-analysis of the Swedish and Norwegian cohorts, we found high signals for association between primary SS and SNPs in three gene loci, not previously associated with primary SS. These are the early B-cell factor 1 (EBF1) gene, P=9.9 × 10−5, OR 1.68, the family with sequence similarity 167 member A–B-lymphoid tyrosine kinase (FAM167A–BLK) locus, P=4.7 × 10−4, OR 1.37 and the tumor necrosis factor superfamily (TNFSF4=Ox40L) gene, P=7.4 × 10−4, OR 1.34. We also confirmed the association between primary SS and the IRF5/TNPO3 locus and the STAT4 gene. We found no association between the SNPs in these five genes and the presence of anti-SSA/anti-SSB antibodies. EBF1, BLK and TNFSF4 are all involved in B-cell differentiation and activation, and we conclude that polymorphisms in several susceptibility genes in the immune system contribute to the pathogenesis of primary SS.
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46.
  • OLSSON, PETER, et al. (författare)
  • Multiplex cytokine analyses in patients with rheumatoid arthritis require use of agents blocking heterophilic antibody activity
  • 2017
  • Ingår i: Scandinavian Journal of Rheumatology. - : Informa UK Limited. - 0300-9742 .- 1502-7732. ; 46:1, s. 1-10
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: Heterophilic antibodies, such as rheumatoid factor (RF), are known to interfere with enzyme-linked immunosorbent assays (ELISAs). Treatment of rheumatoid arthritis (RA) with tumour necrosis factor (TNF)- blockers is well established. The aims of this study were to develop a protocol for blocking the interaction of present heterophilic antibodies and to validate this procedure by evaluating the effect on correlations of cytokine levels to clinical response in RA patients treated with adalimumab.Method: Fourteen patients with active RA were evaluated at baseline and 3 months after starting adalimumab treatment. Cytokines were analysed with a commercial 12-plex bead ELISA. To block interference by RF, a commercial blocker (HeteroBlock) was used. To determine the optimal concentration of HeteroBlock, patient sera were analysed with different concentrations of HeteroBlock. Subsequently, baseline and follow-up sera from the 14 patients were analysed and correlated with clinical outcome.Results: Measured cytokine levels were reduced in the majority of samples when adding the blocker. The optimal concentration of HeteroBlock was 1600 g/mL of serum. Sera with high RF levels were more prone to produce false positive values, although some RF-negative sera also demonstrated evidence of interference. HeteroBlock did not interfere with the analysis. In RA patients treated with adalimumab, changes in interleukin (IL)-6 levels between baseline and follow-up correlated with changes in erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) in sera with added HeteroBlock.Conclusions: When analysing sera from patients with RA with multiplex bead ELISA, the assay should be evaluated for interference by heterophilic antibodies, and if present corrected with, for example, HeteroBlock.
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47.
  • Pehrson, Caroline, et al. (författare)
  • Adhesion of Plasmodium falciparum infected erythrocytes in ex vivo perfused placental tissue : A novel model of placental malaria
  • 2016
  • Ingår i: Malaria Journal. - : Springer Science and Business Media LLC. - 1475-2875. ; 15:1, s. 1-12
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Placental malaria occurs when Plasmodium falciparum infected erythrocytes sequester in the placenta. Placental parasite isolates bind to chondroitin sulphate A (CSA) by expression of VAR2CSA on the surface of infected erythrocytes, but may sequester by other VAR2CSA mediated mechanisms, such as binding to immunoglobulins. Furthermore, other parasite antigens have been associated with placental malaria. These findings have important implications for placental malaria vaccine design. The objective of this study was to adapt and describe a biologically relevant model of parasite adhesion in intact placental tissue. Results: The ex vivo placental perfusion model was modified to study adhesion of infected erythrocytes binding to CSA, endothelial protein C receptor (EPCR) or a transgenic parasite where P. falciparum erythrocyte membrane protein 1 expression had been shut down. Infected erythrocytes expressing VAR2CSA accumulated in perfused placental tissue whereas the EPCR binding and the transgenic parasite did not. Soluble CSA and antibodies specific against VAR2CSA inhibited binding of infected erythrocytes. Conclusion: The ex vivo model provides a novel way of studying receptor-ligand interactions and antibody mediated inhibition of binding in placental malaria.
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48.
  • Rusakiewicz, Sylvie, et al. (författare)
  • NCR3/NKp30 contributes to pathogenesis in primary Sjogren's syndrome.
  • 2013
  • Ingår i: Science translational medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6242 .- 1946-6234. ; 5:195
  • Tidskriftsartikel (refereegranskat)abstract
    • Primary Sjögren's syndrome (pSS) is a chronic autoimmune disease characterized by a lymphocytic exocrinopathy. However, patients often have evidence of systemic autoimmunity, and they are at markedly increased risk for the development of non- Hodgkin's lymphoma. Similar to other autoimmune disorders, a strong interferon (IFN) signature is present among subsets of pSS patients, although the precise etiology remains uncertain. NCR3/NKp30 is a natural killer (NK)-specific activating receptor regulating the cross talk between NK and dendritic cells and type II IFN secretion. We performed a case-control study of genetic polymorphisms of the NCR3/NKp30 gene and found that rs11575837 (G>A) residing in the promoter was associated with reduced gene transcription and function as well as protection to pSS. We also demonstrated that circulating levels of NCR3/NKp30 were significantly increased among pSS patients compared with controls and correlated with higher NCR3/NKp30 but not CD16-dependent IFN-γ secretion by NK cells. Excess accumulation of NK cells in minor salivary glands correlated with the severity of the exocrinopathy. B7H6, the ligand of NKp30, was expressed by salivary epithelial cells. These findings suggest that NK cells may promote an NKp30-dependent inflammatory state in salivary glands and that blockade of the B7H6/NKp30 axis could be clinically relevant in pSS.
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49.
  • Ruseckas, A., et al. (författare)
  • Luminescence from inter-chain aggregates in polythiophene films
  • 2001
  • Ingår i: Synthetic Metals. - 0379-6779 .- 1879-3290. ; 119:1-3, s. 603-604
  • Tidskriftsartikel (refereegranskat)abstract
    • We report time-resolved photoluminescence of two polythiophene derivatives with different chain packing. Emission of inter-chain aggregates is distinguished from that of intra-chain singlet excitons. The aggregate luminescence is shifted towards lower energies relative to that of intra-chain exciton by 0.17 eV, and the Huang-Rhys factor of the coupling to the intra-chain C double bondC vibration is S = 1.5. The excitonic coupling in aggregates is of intermediate strength.
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