| 1. |
- Bengtsson, Karin, 1980
(author)
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Cardiovascular outcomes and extra-articular manifestations in patients with spondyloarthritis
- 2020
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Doctoral thesis (other academic/artistic)abstract
- Background: Spondyloarthritis (SpA) is a cluster of rheumatic diseases with similar clinical features, including association with extra-articular manifestations such as anterior uveitis (AU), inflammatory bowel disease (IBD) and psoriasis. Ankylosing spondylitis (AS), psoriatic arthritis (PsA) and undifferentiated SpA (uSpA) are the major subtypes of SpA. Chronic inflammatory diseases are potential risk factors for cardiovascular disease (CVD). The risk of CVD events in the different SpA subtypes has not been analysed in the same setting in large populations. Further, SpA has been linked to specific cardiovascular manifestations such as aortic regurgitation and cardiac conduction disturbances (CCDs). Objectives: The aims with this thesis were to: A) calculate the incidence of acute coronary syndrome (ACS), stroke, venous thromboembolism (VTE), cardiac rhythm disturbances, aortic regurgitation, AU, IBD and psoriasis in patients with AS, PsA and uSpA in comparison to each other and to controls from general population (GP), B) describe electrocardiographic (ECG) development in AS and to identify associations between baseline characteristics and CCDs at five-year follow-up. Methods: A) Cohorts of patients and controls from GP were identified and followed prospectively through a nationwide and comprehensive linkage of the Swedish health care and population registers. Incidence rates (IRs), events per 1000 person-years at risk, were calculated and standardized to the age and sex distribution in GP. For comparison of the cohorts, Cox regression, with age/sex-adjusted hazard ratios (HRs), and Poisson regression, with incidence rate ratios (IRRs), analyses were performed. B) A longitudinal cohort study of 172 patients with AS examined with ECG in 2009 and after five year in 2014. Logistic regression analyses were performed to identify if baseline characteristics were associated with a CCD at five-year follow-up. Results: A significantly increased risk of all studied cardiovascular outcomes was demonstrated in SpA in comparison to GP. For ACS, stroke and VTE, the age/sex-adjusted HR point estimates in the SpA subtypes ranged between 1.4 to 1.8, 1.2 to 1.3 and 1.5 to 1.5, respectively. The increased relative risk of ACS was especially pronounced in women with PsA (age-adjusted HR 2.0). Regarding cardiac rhythm disturbances, the highest absolute risk (IRs) was noted for atrial fibrillation (5.5 to 7.4 events per 1000 person-years), whereas the highest relative risk vs GP was found for AV block II-III in men with uSpA (age-adjusted HR 4.2) and AS (age-adjusted HR 2.5). In patients with AS, uSpA and PsA vs matched controls, relative risks (IRRs) were significantly increased for AU (20.2, 13.6 and 2.5), IBD (6.2, 5.7 and 2.3) and psoriasis (2.5, 3.8 and not applicable). In the ECG study, 13% had a CCD at follow-up. In age/sex-adjusted analyses; CCD at baseline, male sex, history of AU, higher AS disease activity score based on CRP, greater waist circumference, medication with anti-platelets and beta-blockers were associated with a CCD at five-year follow-up. Higher age/longer AS symptom duration was also associated with a CCD. Conclusions: Patients with SpA have an increased risk of different manifestations of CVD including ACS and stroke in comparison to general population. These results underscore the need to implement strategies to improve CVD risk factors management in clinical practice for patients with SpA irrespective of subtype. Further, AS characteristics as well as markers of CVD were associated with the presence of CCD. Last, a strong association for AU and IBD was noted in AS, closely followed by uSpA, whereas the association for these manifestations was considerably weaker in PsA.
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| 2. |
- Bengtsson, Karin, 1980, et al.
(author)
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Incidence of extra-articular manifestations in ankylosing spondylitis, psoriatic arthritis and undifferentiated spondyloarthritis : Results from a national register-based cohort study
- 2021
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In: Rheumatology (United Kingdom). - : Oxford University Press (OUP). - 1462-0324 .- 1462-0332. ; 60:6, s. 2725-2734
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Journal article (peer-reviewed)abstract
- Objectives: To estimate the incidence and strength of association of extra-articular manifestations [EAMs, here: anterior uveitis (AU), IBD and psoriasis] in patients with AS, undifferentiated SpA (uSpA) and PsA, compared with controls. Methods: Three mutually exclusive cohorts of patients aged 18-69 years with AS (n = 8517), uSpA (n = 10 245) and PsA (n = 22 667) were identified in the Swedish National Patient Register 2001-2015. Age-, sex- and geography-matched controls were identified from the Swedish Population Register. Follow-up began 1 January 2006, or six months after the first SpA diagnosis, whichever occurred later, and ended at the first date of the EAM under study, death, emigration, 70 years of age, and 31 December 2016. Incidence rates (IRs) and incidence rate ratios were calculated for each EAM, and stratified by sex and age. Results: Incidence rate ratios for incident AU, IBD and psoriasis were significantly increased in AS (20.2, 6.2, 2.5), uSpA (13.6, 5.7, 3.8) and PsA (2.5, 2.3, n.a) vs controls. Men with AS and uSpA had significantly higher IRs per 1000 person-years at risk for incident AU than women with AS (IR 15.8 vs 11.2) and uSpA (IR 10.1 vs 6.0), whereas no such sex difference was demonstrated in PsA or for the other EAMs. Conclusions: AU, followed by IBD and psoriasis, is the EAM most strongly associated with AS and uSpA. Among the SpA subtypes, AS and uSpA display a largely similar pattern of EAMs, whereas PsA has a considerably weaker association with AU and IBD.
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| 3. |
- Bengtsson, Karin, 1980, et al.
(author)
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Occurrence and relative risks for non-vertebral fractures in patients with ankylosing spondylitis compared with the general population: a register-based study from Sweden
- 2023
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In: Rmd Open. - : BMJ. - 2056-5933. ; 9:1
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Journal article (peer-reviewed)abstract
- ObjectivesTo estimate the incidence of non-vertebral fractures in ankylosing spondylitis (AS) compared with the general population.MethodsNationwide register-based cohort study including patients with AS (n=11 611, 65% men, mean age 48 years), and matched general population controls (n=58 050). Five prespecified fracture outcomes: (1) non-vertebral; (2) fracture of the proximal humerus, distal forearm or hip; (3) proximal humerus; (4) distal forearm and (5) hip) were identified through register linkages with follow-up 2007-2016. We used Poisson regression to calculate incidence rates (IRs), number of fractures per 1000 person-years at risk and IR ratios (IRRs), overall and by sex and age. IRRs were adjusted for history of any prior fracture.ResultsIRs (men/women) for non-vertebral fracture in AS were 11.9 (95% CI 11.0 to 12.9)/14.5 (95% CI 13.1 to 16.1) and in controls 10.0 (95% CI 9.7 to 10.4)/11.8 (95% CI 11.1 to 12.4), IRR (men/women) 1.2 (95% CI 1.1 to 1.3)/1.2 (95% CI 1.1 to 1.4). IRs (men/women) for fractures of the humerus, forearm or hip in AS were 4.0 (95% CI 3.5 to 4.6)/6.3 (95% CI 5.4 to 7.3) and in controls 2.7 (95% CI 2.5 to 2.9)/5.5 (95% CI 5.1 to 6.0), IRR (men/women) 1.5 (95% CI 1.3 to 1.7)/1.1 (95% CI 0.9 to 1.3). IRRs were statistically significantly elevated in men with AS versus controls for forearm fracture (1.4 (95% CI 1.1 to 1.7)) and hip fracture (1.8 (95% CI 1.4 to 2.3)), whereas not in women with AS where the IRRs were 1.1 (95% CI 0.9 to 1.4) and 1.0 (95% CI 0.6 to 1.4). For humerus fracture, IRRs were 1.4 (95% CI 0.99 to 1.9) in men with AS versus controls and 1.1 (95% CI 0.8 to 1.6) in women.ConclusionsBoth men and women with AS have a slightly higher risk of non-vertebral fractures than the general population. A statistically significantly higher risk of fractures of the proximal humerus, distal forearm or hip was found in men with AS in comparison to general population, where the relative risk was especially pronounced for hip fracture.
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| 4. |
- Drivelegka, Panagiota, et al.
(author)
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Incident gout and risk of first-time acute coronary syndrome: a prospective, population-based, cohort study in Sweden
- 2023
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In: Arthritis Care and Research. - : Wiley. - 2151-464X .- 2151-4658. ; 75:6, s. 1292-1299
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Journal article (peer-reviewed)abstract
- Objective: To investigate the risk of first-time acute coronary syndrome (ACS) in a large cohort of primary and secondary care patients with incident gout, compared to the general population. Methods: Using register data for the period 2007 ̶ 2017, we conducted a prospective, population-based cohort with 20,146 patients with incident gout (mean age, 65.6 years; 67.4% males) and 83,517 matched population controls, without prior history of coronary heart disease. We calculated incidence rates (IR) and hazard ratios (HR) adjusted for baseline comorbidities and dispensed prescriptions. In a sensitivity analysis, we included gout cases and controls with no previously diagnosed comorbidity (6,075 cases and 44,091 controls). Results: The IR of first-time ACS was significantly increased in the gout cohort, compared to controls (9.1 vs 6.3/1,000 person-years). Unadjusted cox regression showed that gout patients had higher risk of first-time ACS compared to controls (HR, 1.44; 95%CI, 1.33-1.56), with higher HR in women (HR, 1.64; 95%CI, 1.41 ̶ 1.90) than in men (HR, 1.36; 95%CI, 1.24 ̶ 1.50). In multivariable analysis the risk diminished but remained significant (HR, 1.15; 95%CI, 1.06-1.25). The risk was similar in the sensitivity analysis (HR, 1.20; 95%CI, 1.01-1.44), and still higher in women (HR, 1.34; 95%CI, 0.86-2.08), than in men (HR, 1.18; 95%CI, 0.97-1.44). Conclusion: Patients with incident gout have a 44% increased risk of first-time ACS, higher in women than in men. This risk is largely explained by the underlying comorbidities, but there is still a modestly increased risk that may be due to gout-related factors.
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| 5. |
- Lindström, Ulf, et al.
(author)
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Anterior uveitis in patients with spondyloarthritis treated with secukinumab or tumour necrosis factor inhibitors in routine care: does the choice of biological therapy matter?
- 2021
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In: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 80:11, s. 1445-1452
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Journal article (peer-reviewed)abstract
- Background The effect of interleukin 17-inhibitors on anterior uveitis (AU) in spondyloarthritis (SpA) is poorly understood. This study aimed to compare the risk of AU during treatment with secukinumab versus tumour necrosis factor inhibitors (TNFi). Methods Patients with SpA starting secukinumab or a TNFi 2015 through 2018 were identified in the Swedish Rheumatology Quality Register. Occurrence of AU was identified based on diagnosis codes in outpatient ophthalmology care in the National Patient Register. The main outcomes were crude rates of AU-diagnoses per 100 patient-years, and adjusted HRs for AU, during treatment, in patients without AU during the year before treatment start (in order to reduce confounding by indication). HRs were adjusted for age, sex, history of AU and patient global assessment of disease activity. Results Based on 4851 treatment starts (456 secukinumab; 4395 any TNFi), the rate of AU-diagnoses per 100 patient-years was 6.8 (95% CI 5.2 to 8.7) for secukinumab. Among the TNFi, the rate varied from 2.9 (95% CI 2.1 to 3.7) for infliximab and 4.0 (95% CI 3.3 to 4.9) for adalimumab to 7.5 (95% CI 6.7 to 8.4) for etanercept. The adjusted HRs for first AU (adalimumab as reference) were: secukinumab 2.32 (95% CI 1.16 to 4.63), infliximab 0.99 (95% CI 0.49 to 1.96), etanercept 1.82 (95% CI 1.13 to 2.93), golimumab 1.59 (95% CI 0.90 to 2.80) and certolizumab 1.12 (95% CI 0.44 to 2.83). Sensitivity analyses confirmed the pattern of higher AU rates with secukinumab and etanercept versus monoclonal TNFi. Conclusion As used in clinical practice in SpA, secukinumab appears to be associated with a higher risk of AU, compared with the monoclonal TNFi and a similar risk compared with etanercept.
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| 6. |
- Mehta, Bharat, 1993, et al.
(author)
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Thermal Stability In Al-Mn-Cr-Zr Based Aluminium Alloys Tailored For Powder Bed Fusion - Laser Beam
- 2022
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In: World PM 2022 Congress Proceedings.
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Conference paper (peer-reviewed)abstract
- Al-Mn-Cr-Zr family of alloys tailored for powder bed fusion - laser beam process have been developed by the authors. The alloys were designed by leveraging negligible solidification range close to solidification, leading to an "inherently crack free" alloy system. These alloys have been designed to benefit from higher amount of solutes in solid solution, which leads to stronger precipitation hardening via direct ageing to achieve high strengths. Since the alloying elements were selected having low bulk diffusivities, slower precipitation kinetics is expected which suggests retention of high strength even after secondary ageing post peak hardening. Upon secondary ageing the alloys at 523K for 2544 hours and 623K 1054 hours negligible hardness loss at 523K and 17 HV loss at 623K was observed. This was benchmarked against Scalmalloy® which was seen to have negligible hardness loss at 523K and 28 HV loss at 623 K respectively.
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| 7. |
- Riabov, Dmitri, 1990, et al.
(author)
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Design and characterization of a cobalt-free stainless maraging steel for laser-based powder bed fusion
- 2022
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In: Materials and Design. - : Elsevier BV. - 1873-4197 .- 0264-1275. ; 223
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Journal article (peer-reviewed)abstract
- This study presents a new Co-free stainless maraging variant for laser-based powder bed fusion developed using a computational alloy design approach. The goal was to develop an easily printable material with similar performance to 18Ni-300. After screening numerous compositions, Fe-13.2Cr-9.1Ni-1.1Al-0.6Mo-0.5Nb-0.23Ti-0.5Mn-0.5Si (wt.%) was selected. This composition showed excellent printability with low porosity levels. The precipitation strengthening response was evaluated by aging at 500 °C for 15 min, 3 h and 18 h, measuring hardness, tensile strength, and by characterization using atom probe tomography. After 15 min of aging, 90% of the maximum hardness was reached, thanks to formation of (Ni, Al, Nb, Ti, Mn, Si) clusters with a density of 1.5 × 1024 m-3. Between 15 min and 3 h, distinct precipitates formed with a radius of ∼1.4 nm. The precipitates underwent a splitting phenomenon after 18 h, forming several unique Ni-rich precipitates including Ni16Si7(Ti, Nb)6 and Ni3(Al, Ti, Nb, Si). The splitting can be a reason for the slow coarsening rate, as the average precipitate radius after 18 h was only 2 nm. Simulations of the precipitation sequence using PRISMA indicated very rapid and dense precipitation of L12-Ni3X precipitates with a slow coarsening rate, in agreement with experimental observations.
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| 8. |
- Strålin, Kristoffer, et al.
(author)
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Design of a national patient-centred clinical pathway for sepsis in Sweden
- 2023
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In: Infectious Diseases. - : Taylor & Francis. - 2374-4235 .- 2374-4243. ; 55:10, s. 716-724
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Journal article (peer-reviewed)abstract
- BACKGROUND: The World Health Organization has adopted a resolution on sepsis and urged member states to develop national processes to improve sepsis care. In Sweden, sepsis was selected as one of the ten first diagnoses to be addressed, when the Swedish government in 2019 allocated funds for patient-centred clinical pathways in healthcare. A national multidisciplinary working group, including a patient representative, was appointed to develop the patient-centred clinical pathway for sepsis.METHODS: The working group mapped challenges and needs surrounding sepsis care and included a survey sent to all emergency departments (ED) in Sweden, and then designed a patient-centred clinical pathway for sepsis.RESULTS: The working group decided to focus on the following four areas: (1) sepsis alert for early detection and management optimisation for the most severely ill sepsis patients in the ED; (2) accurate sepsis diagnosis coding; (3) structured information to patients at discharge after sepsis care and (4) structured telephone follow-up after sepsis care. A health-economic analysis indicated that the implementation of the clinical pathway for sepsis will most likely not drive costs. An important aspect of the clinical pathway is implementing continuous monitoring of performance and process indicators. A national working group is currently building up such a system for monitoring, focusing on extraction of this information from the electronic health records systems.CONCLUSION: A national patient-centred clinical pathway for sepsis has been developed and is currently being implemented in Swedish healthcare. We believe that the clinical pathway and the accompanying monitoring will provide a more efficient and equal sepsis care and improved possibilities to monitor and further develop sepsis care in Sweden.
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| 9. |
- Södergren, Anna, 1977-, et al.
(author)
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Characteristics and outcome of a first acute myocardial infarction in patients with ankylosing spondylitis
- 2021
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In: Clinical Rheumatology. - : Springer Science and Business Media LLC. - 0770-3198 .- 1434-9949. ; 40, s. 1321-1329
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Journal article (peer-reviewed)abstract
- Objectives To study clinical characteristics, mortality, and secondary prevention, after a first incident acute myocardial infarction (AMI) in patients with ankylosing spondylitis (AS) compared with the general population. Methods In total, 292 subjects with AS and a first AMI between Jan 2006 and Dec 2014 were identified using the Swedish national patient register. Each subject was matched with up to 5 general population comparators per AS-patient (n = 1276). Follow-up started at the date of admission for AMI and extended until death or 365 days of follow-up. Cox regression was used to assess mortality in two time intervals: days 0-30 and days 31-365. For a subgroup with available data, clinical presentation at admission, course, treatment for AMI, and secondary prevention were compared. Results During the 365-day follow-up, 56/292 (19%) AS patients and 184/1276 (14%) comparators died. There were no difference in mortality due to cardiovascular-related causes, although the overall mortality day 31-365 was increased among patients with AS compared with comparators (HR [95% CI] = 2.0 [1.3;3.0]). At admission, AS patients had a higher prevalence of cardiovascular comorbidities compared with comparators. At discharge, patients with AS were less often prescribed lipid-lowering drugs and non-aspirin antiplatelet therapy. Conclusions Patients with AS tend to have a higher comorbidity burden at admission for first AMI. The mortality after a first AMI due to cardiovascular-related causes does not seem to be elevated, despite an increased overall mortality during days 31-365 among patients with AS compared with the general population.
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