| 21. |
- Ekman, Carl Johan, et al.
(author)
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Outcome of transcranial magnetic intermittent theta-burst stimulation in the treatment of depression - A Swedish register-based study
- 2023
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In: Journal of Affective Disorders. - : Elsevier. - 0165-0327 .- 1573-2517. ; 329, s. 50-54
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Journal article (peer-reviewed)abstract
- BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is an established treatment of depression. The more recently introduced intermittent Theta-burst stimulation (iTBS) has shown significant superiority over sham-stimulation and equal effect sizes to a 10 Hz protocol in one clinical trial. The aim of the current study was to investigate the effectiveness and tolerability of iTBS in a naturalistic, clinical setting. Further, we explored demographical and clinical predictors of response.METHODS: Data was collected from seventeen rTMS-sites in Sweden between January 2018 and May 2021, through the Swedish National Quality register for repetitive Transcranial Magnetic Stimulation (Q-rTMS). We included 542 iTBS-treated patients with unipolar or bipolar depression. Outcome was assessed with Clinical Global Impression Severity and Improvement scores in an intention to treat analysis.RESULTS: The response rate was 42.1 % and 16.1 % reached remission. The response rate was significantly larger in the oldest age group compared to the youngest (odds ratio 3.46, 95 % confidence interval 1.65-7.22). Less severe level of depression (Montgomery-Åsberg depression rating scale self-assessment < 36) at baseline predicted response and remission. Only <1 % were much or very much worse after treatment. Drop-out rate was 10.9 %. No serious adverse events were reported.LIMITATIONS: Retrospective analysis of register data. No comparison group.CONCLUSIONS: In a clinical setting, iTBS was shown to be safe and tolerable and the response rate was similar to that reported from clinical trials. Older age-group and less severe illness predicted response.
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| 22. |
- Fernandes-Cerqueira, Catia, et al.
(author)
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Targeting of anti-citrullinated protein/peptide antibodies in rheumatoid arthritis using peptides mimicking endogenously citrullinated fibrinogen antigens
- 2015
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In: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6362 .- 1478-6354. ; 17
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Journal article (peer-reviewed)abstract
- Introduction: We have previously identified endogenously citrullinated peptides derived from fibrinogen in rheumatoid arthritis (RA) synovial tissues. In this study, we have investigated the auto-antigenicity of four of those citrullinated peptides, and explored their feasibility to target anti-citrullinated protein/peptide antibodies (ACPA). Methods: The autoantigenic potential of the fibrinogen peptides was investigated by screening 927 serum samples from the Epidemiological Investigation of RA (EIRA) cohort on a peptide microarray based on the ImmunoCAP ISAC (R) system. In order to assay for ACPA blocking, two independent pools of purified ACPA were incubated with the respective targeting peptide prior to binding to cyclic citrullinated peptide (CCP) 2 using the CCPlus (R) ELISA kit. Results: Two peptides derived from the fibrinogen a chain, Arg573Cit (563-583) and Arg591Cit (580-600), referred to as Cit573 and Cit591, and two peptides from the fibrinogen beta chain, Arg72Cit (62-81) and Arg74Cit (62-81) (Cit72 and Cit74), displayed 65 %, 15 %, 35 %, and 53 % of immune reactivity among CCP2-positive RA sera, respectively. In CCP2-negative RA sera, a positive reactivity was detected in 5 % (Cit573), 6 % (Cit591), 8 % (Cit72), and 4 % (Cit74). In the competition assay, Cit573 and Cit591 peptides reduced ACPA binding to CCP2 by a maximum of 84 % and 63 % respectively. An additive effect was observed when these peptides were combined. In contrast, Cit74 and Cit72 were less effective. Cyclization of the peptide structure containing Cit573 significantly increased the blocking efficiency. Conclusions: Here we demonstrate extensive autoantibody reactivity against in vivo citrullinated fibrinogen epitopes, and further show the potential use of these peptides for antagonizing ACPA.
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| 23. |
- Galindo-Feria, Angeles S., et al.
(author)
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Proinflammatory Histidyl-Transfer RNA Synthetase-Specific CD4+T Cells in the Blood and Lungs of Patients With Idiopathic Inflammatory Myopathies
- 2020
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In: Arthritis & Rheumatology. - : WILEY. - 2326-5191 .- 2326-5205. ; 72:1, s. 179-191
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Journal article (peer-reviewed)abstract
- Objective Autoantibodies targeting histidyl-transfer RNA synthetase (HisRS; anti-Jo-1) are common in the idiopathic inflammatory myopathies (IIMs) and antisynthetase syndrome. This study was undertaken to investigate immunity against HisRS in the blood and lungs of patients with IIM/antisynthetase syndrome. Methods Bronchoalveolar lavage (BAL) fluid, BAL fluid cells, and peripheral blood mononuclear cells (PBMCs) from patients with IIM/antisynthetase syndrome (n = 24) were stimulated with full-length HisRS protein or a HisRS-derived peptide (HisRS(11-23)). BAL fluid and PBMCs from patients with sarcoidosis (n = 7) and healthy subjects (n = 12) were included as controls. The CD4+ T cell response was determined according to levels of CD40L up-regulation and cytokine expression using flow cytometry. Anti-Jo-1 autoantibody responses in the serum and BAL fluid were assessed by enzyme-linked immunosorbent assay. Lung biopsy samples from patients with IIM/antisynthetase syndrome (n = 14) were investigated by immunohistochemistry. Results In BAL fluid, CD4+ T cells from 3 of 4 patients with IIM/antisynthetase syndrome responded to stimulation with HisRS protein, as measured by the median fold change in CD40L expresssion in stimulated cells compared to unstimulated cells (median fold change 3.6, interquartile range [IQR] 2.7-14.7), and 2 of 3 patients with IIM/antisynthetase syndrome had the highest responses to HisRS(11-23) (median fold change 88, IQR 27-149)(.) In PBMCs, CD4+ T cells from 14 of 18 patients with IIM/antisynthetase syndrome responded to HisRS protein (median fold change 7.38, IQR 2.69-31.86; P < 0.001), whereas a HisRS(11-23) response was present in 11 of 14 patients with IIM/antisynthetase syndrome (median fold change 3.4, IQR 1.87-10.9; P < 0.001). In the control group, there was a HisRS(11-23) response in 3 of 7 patients with sarcoidosis (median fold change 2.09, IQR 1.45-3.29) and in 5 of 12 healthy controls (median fold change 2, IQR 1.89-2.42). CD4+ T cells from patients with IIM/antisynthetase syndrome displayed a pronounced Th1 phenotype in the BAL fluid when compared to the PBMCs (P < 0.001), producing high amounts of interferon-gamma and interleukin-2 following stimulation. Anti-Jo-1 autoantibodies were detected in BAL fluid and germinal center (GC)-like structures were seen in the lung biopsy samples from patients with IIM/antisynthetase syndrome. Conclusion The results of this study demonstrate a pronounced presence of HisRS-reactive CD4+ T cells in PBMCs and BAL fluid cells from patients with IIM/antisynthetase syndrome as compared to patients with sarcoidosis and healthy controls. These findings, combined with the presence of anti-Jo-1 autoantibodies in BAL fluid and GC-like structures in the lungs, suggest that immune activation against HisRS might take place within the lungs of patients with IIM/antisynthetase syndrome.
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| 24. |
- Gillving, Cecilia, 1999-, et al.
(author)
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Seizure Duration and Electroconvulsive Therapy in Major Depressive Disorder
- 2024
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In: JAMA Network Open. - : AMER MEDICAL ASSOC. - 2574-3805. ; 7:7
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Journal article (peer-reviewed)abstract
- IMPORTANCE Electroconvulsive therapy (ECT), wherein a generalized epileptic seizure is induced, is a treatment for major depressive disorder (MDD). Currently, it is unclear whether there is an association between seizure length and treatment outcome. OBJECTIVE To explore the association between seizure duration, potential confounding variables, and ECT treatment outcome. DESIGN, SETTING, AND PARTICIPANTS This population-based cohort study obtained data from the Swedish National Quality Register for ECT. Patients treated for unipolar MDD with unilateral electrode placement between January 1, 2012, and December 31, 2019, were included. The electroencephalographic (EEG) seizure duration from the first ECT treatment session for each patient was used for analysis. Data analyses were performed between March 2021 and May 2024. MAIN OUTCOMES AND MEASURESThe primary outcome was remission, defined as a cutoff score of less than 10 points on the self-assessment version of the Montgomery-& Aring;sberg Depression Rating Scale within 1 week after ECT. Multivariate logistic regression analysis was performed to calculate odds ratios (ORs) between different seizure duration groups. Furthermore, the associations between concomitant use of pharmacological treatments, seizure duration, and remission rate were explored. RESULTS Among the 6998 patients included, 4229 (60.4%) were female and the mean (SD) age was 55.2 (18.6) years. Overall, 2749 patients (39.3%) achieved remission after ECT. Patients with EEG seizure duration of 60 to 69 seconds had the highest remission rates compared with patients with seizure duration of less than 20 seconds (OR, 2.17; 95% CI, 1.63-2.88; P < .001). Anticonvulsant medications were associated with shorter seizure duration (eg, lamotrigine: beta coefficient [SE], -6.02 [1.08]; P < .001) and lower remission rates (eg, lamotrigine: adjusted OR, 0.67; 95% CI, 0.53-0.84; P < .001). CONCLUSIONS AND RELEVANCE This study found an association between seizure length and remission from MDD. Use of anticonvulsant medication during ECT was associated with shorter seizure duration and lower remission rates after ECT.
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| 25. |
- Granlund, David, 1979-, et al.
(author)
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Det offentliga som konkurrent på kommersiella marknader - En samhällsekonomisk analys med exemplet konferensmarknaden
- 2017
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Reports (other academic/artistic)abstract
- I den här rapporten analyseras samhällsekonomiska effekter av att det offentliga konkurrerar med privata företag på kommersiella marknader. Den innehåller även en pilotstudie av marknaden för en – och tvådagarskonferenser tillämpad på Umeåregionen.Svensk konkurrenslagstiftning inkluderar regler om konkurrensbegränsande offentlig säljverksamhet. Reglerna gäller för den offentliga sektorn i sin helhet, dvs stat, primärkommuner (kommun) eller landstingskommuner (landsting) och juridiska personer vars verksamhet den offentliga sektorn har ett dominerande inflytande över. Inflytandet kan ta sig formen av ägande, finansieringsvillkor, styrelse, lag och avtal. Frågan om det offentliga som konkurrent är även samhällsekonomiskt relevant då snedvridning av konkurrens i form av exempelvis underprissättning till följd av stöd, kan innebära en samhällsekonomisk förlust.Sammantaget visar den samhällsekonomiska analysen att det inte går att dra några generella slutsatser om att konkurrens från den offentliga sektorn på marknader med en etablerad kommersiell verksamhet alltid är problematisk. Även i situationer där konkurrensen sker på olika villkor kan fördelarna med den offentliga aktörens medverkan överväga nackdelarna. Baserat på pilotstudien och olika scenarios avseende konferensmarknaden i Umeå, är det möjligt att dra slutsatsen att fördelarna med offentliga aktörer kan dominera nackdelarna under förutsättning att den offentliga aktörens produktionskostnad maximalt är en procent högre än en privat aktörs produktionskostnad för motsvarande konferens. Analysen visar att subventioner till offentliga aktörer överskridande 1,3 miljoner kronor inte kan motiveras utifrån ett samhällsekonomiskt perspektiv i något scenario. I scenariot där den offentliga aktören ägnar sig åt underprissättning överväger nackdelarna även om verksamheten klarar sig utan subvention.
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| 26. |
- Güney, Pelin, et al.
(author)
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Electroconvulsive Therapy in Depression : Improvement in Quality of Life Depending on Age and Sex
- 2020
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In: Journal of ECT. - : Lippincott Williams & Wilkins. - 1095-0680 .- 1533-4112. ; 36:4, s. 242-246
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Journal article (peer-reviewed)abstract
- OBJECTIVES: It is uncertain if there are variations in the improvement of quality in life between sexes and age groups after electroconvulsive therapy (ECT). The aim of this study was to investigate how health-related quality of life changed after treatment and to examine differences in the results between sex and age groups.METHODS: This register-based study used data from the Swedish national quality register for ECT. The study population was patients diagnosed with depression who had received ECT. Health-related quality of life was quantified using the 3-level version the EuroQol 5-dimensional questionnaire (EQ-5D 3 L). Analysis of variance was used to compare change in EQ-5D score from pretreatment to posttreatment between sex and age groups.RESULTS: There was a statistically significant improvement in EQ-5D index score and EQ visual analog scale (VAS) score in all patient groups after ECT. The mean improvement in EQ-5D index score and EQ-VAS score ranged from 0.31 to 0.46 and 28.29 to 39.79, respectively. Elderly patients had greater improvement in EQ-5D index score and EQ-VAS score than younger patients. There was no significant difference in improvement between the sexes. The mean improvement in EQ-5D index score was 0.40 for male patients and 0.41 for female patients.CONCLUSIONS: Electroconvulsive therapy had a considerable effect on health-related quality of life in patients with depression of both sexes and all age groups. The improvement was greatest in elderly patients, who more often had psychotic features. More studies are needed to investigate the long-term effects of ECT and to further explain the varying treatment results between elderly and younger patients.
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| 27. |
- Göterfelt, Linda, et al.
(author)
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The Incidence of Dental Fracturing in Electroconvulsive Therapy in Sweden
- 2020
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In: Journal of ECT. - : Lippincott Williams & Wilkins. - 1095-0680 .- 1533-4112. ; 36:3, s. 168-171
-
Journal article (peer-reviewed)abstract
- OBJECTIVES: One adverse effect of electroconvulsive therapy (ECT) is dental fracture; thus, a bite guard and muscle relaxants are used to prevent it. Earlier research reported varying rates of dental fracture, but there is no large-scale study on the incidence of dental fracture during ECT. This study aimed to examine the incidence of dental fracture during ECT and to investigate whether the incidence differs between different sexes, age groups, diagnosis groups, electrode placements, or number of treatment sessions.METHODS: This register-based study used data from the Swedish national quality register for ECT. All hospitals offering ECT report to this register, and the coverage ratio is about 90%. All registered patients who started an ECT series between January 2012 and January 2019 were included in this study, with the data representing 16,681 individuals, 38,862 series, and 254,906 sessions.RESULTS: Forty-six dental fractures were identified, giving an incidence of dental fracture of 0.2% per series, 0.02% per session, and 0.3% per individual. We did not find any significant associations between dental fracture rates and male or female populations, age, or different diagnosis groups, nor was there any significant difference between dental fracture rates and electrode placement. The mean number of treatments was significantly higher in the dental fracture group than in patients without dental fracture.CONCLUSIONS: There is a minimal risk of dental fracture during ECT. Our findings, together with those of other studies, provide further motivation for the use of a bite guard and muscle relaxant.
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| 28. |
- Hansson, Monika, et al.
(author)
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Validation of a multiplex chip-based assay for the detection of autoantibodies against citrullinated peptides
- 2012
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In: ARTHRITIS RESEARCH & THERAPY. - : Springer Science and Business Media LLC. - 1478-6354 .- 1478-6362. ; 14:5, s. R201-
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Journal article (peer-reviewed)abstract
- Introduction: Autoantibodies directed against citrullinated proteins/peptides (ACPAs) are highly specific and predictive for the development of rheumatoid arthritis (RA). Different subgroups of RA patients, which have different prognoses and may require different treatments, are characterized by different autoantibody profiles. The objective of this study was to develop a microarray for the detection of multiple RA-associated autoantibodies, initially focusing on responses against citrullinated epitopes on candidate autoantigens in RA. Methods: The microarray is based on Phadia's ImmunoCAP ISAC system, with which reactivity to more than 100 antigens can be analyzed simultaneously, by using minute serum volumes (<10 mu l). Twelve citrullinated peptides, and the corresponding native arginine-containing control peptides, were immobilized in an arrayed fashion onto a chemically modified glass slide, allowing a three-dimensional layer with high binding capacity. The assay was optimized concerning serum dilution and glass surface, whereas each individual antigen was optimized concerning coupling chemistry, antigen concentration, and selection of spotting buffer. The performance of each peptide in the ImmunoCAP ISAC system was compared with the performance in enzyme-linked immunosorbent assays (ELISAs). Serum from 927 RA patients and 461 healthy controls from a matched case-control study were applied onto reaction sites on glass slides, followed by fluorescent-labeled anti-human immunoglobulin G (IgG) antibody. Fluorescence intensities were detected with a laser scanner, and the results analyzed by using image-analysis software. Results: Strong correlations between the ImmunoCAP ISAC system and ELISA results were found for individual citrullinated peptides (Spearman rho typically between 0.75 and 0.90). Reactivity of RA sera with the peptides was seen mainly in the anticyclic citrullinated peptide 2 (CCP2)-positive subset, but some additional reactivity with single citrullinated peptides was seen in the anti-CCP2-negative subset. Adjusting for reactivity against arginine-containing control peptides did not uniformly change the diagnostic performance for antibodies against the individual citrullinated peptides. Conclusions: The multiplexed array, for detection of autoantibodies against multiple citrullinated epitopes on candidate RA autoantigens, will be of benefit in studies of RA pathogenesis, diagnosis, and potentially as a guide to individualized treatment.
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| 29. |
- Holmberg, Johan, 1994-
(author)
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Essays on earnings formation, labor market dynamics, and taxation
- 2021
-
Doctoral thesis (other academic/artistic)abstract
- Chapter [I] analyses the dynamic properties of life-cycle earnings of men and women in Sweden by fitting a model to the covariance structure of earnings. We find that the financial crisis of 2008 did not have any major impact on the variability of earnings and that the upward trend in permanent earnings inequality observed in Sweden during the 1990s does not continue in the 2000s. Using the model to simulate the accumulation of income pension entitlements, we find that college-educated workers have smaller variations in pension entitlements than workers with less education.Chapter [II] presents a life-cycle earnings dynamics model that includes endogenous employment and job change. The model is estimated on Swedish register data using indirect inference. By simulating data from this model, we study the macroeconomic consequences of transitory shocks to unemployment risk, how unemployment at different ages affects the accumulation of pension entitlements, and analyze how different factors contribute to earnings inequality. We find that transitory aggregate shocks to unemployment risk have long-lasting negative effects on employment and earnings, that becoming unemployed at age 40 has a large negative effect on pension accumulations, and that unobserved individual heterogeneity contributes substantially to the observed life-cycle earnings inequality for both men and women in Sweden.Chapter [III] presents a model of earnings dynamics that includes transitions in and out of employment and business cycle fluctuations. The model is estimated using indirect inference and a mix of Swedish register, survey and macro data. We find that the transitions from unemployment to employment are more sensitive to business cycle fluctuations than the probability of remaining employed. By simulating data from the model, we find that the business cycle has a relatively small impact on earnings inequality in Sweden and that young workers are more sensitive to business cycle fluctuations than older workers.Chapter [IV] deals with optimal nonlinear taxation of income and profits in a general equilibrium model with frictional unemployment. We find that the government can achieve redistribution of income through taxation without distorting production efficiency. This outcome is possible if the government uses two nonlinear tax instruments, taxing profits and labor income separately. The results also show that including involuntary unemployment creates an incentive to tax entrepreneurial income at lower marginal rates and labor income at higher marginal rates than otherwise.
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| 30. |
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