| 1. |
- Albadri, Zeyad, et al.
(författare)
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Incidence of Dermatitis Herpetiformis in Sweden 2005 to 2018 : A Nationwide Retrospective Cohort Study
- 2023
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Ingår i: Acta Dermato-Venereologica. - : ACTA DERMATO-VENEREOLOGICA. - 0001-5555 .- 1651-2057. ; 103
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Tidskriftsartikel (refereegranskat)abstract
- Dermatitis herpetiformis has been investigated in the past; however, only a limited number of studies have reported its incidence based on validated nationwide population-based registries. To address this gap, the aims of this study are to estimate the incidence of dermatitis herpetiformis in Sweden and to validate the National Patient Register (NPR) for diagnosis of dermatitis herpetiformis. A population-based open cohort study was conducted, including all patients diagnosed with dermatitis herpetiformis (International Classification of Diseases 10th revision; ICD-10 code L13.0) in Sweden from 2005 to 2018 (n = 1,724), identified from the NPR. The diagnosis of dermatitis herpetiformis in the NPR was validated using medical records, histopathological and immunopathological data, yielding a positive predictive value (PPV) of 62.5%. The mean annual incidence of dermatitis herpetiformis was 0.93/100,000 (95% confidence interval 0.79–1.08), female to male ratio 1:1, and mean age at diagnosis 60.9 years. In conclusion, this large nationwide cohort study showed a low validity for diagnosis of dermatitis herpetiformis in the NPR, and the adjusted incidence rate of dermatitis herpetiformis in Sweden was estimated to be 0.93/100,000, which is lower than that in previous Swedish studies.
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| 2. |
- Andersson, Helene, 1983, et al.
(författare)
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The influence of the molecular weight of the water-soluble polymer on phase-separated films for controlled release
- 2016
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Ingår i: International Journal of Pharmaceutics. - : Elsevier BV. - 0378-5173 .- 1873-3476. ; 511:1, s. 223-235
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Tidskriftsartikel (refereegranskat)abstract
- Hydroxypropyl cellulose (HPC) and ethyl cellulose (EC) can be used for extended release coatings, where the water-soluble HPC may act as a pore former. The aim was to investigate the effect of the molecular weight of HPC on the microstructure and mass transport in phase-separated freestanding EC/HPC films with 30% w/w HPC. Four different HPC grades were used, with weight averaged molecular weights (Mw) of 30.0 (SSL), 55.0 (SL), 83.5 (L) and 365 (M) kg/mol. Results showed that the phase-separated structure changed from HPC-discontinuous to bicontinuous with increasing Mw of HPC. The film with the lowest Mw HPC (SSL) had unconnected oval-shaped HPC-rich domains, leaked almost no HPC and had the lowest water permeability. The remaining higher Mw films had connected complex-shaped pores, which resulted in higher permeabilities. The highest Mw film (M) had the smallest pores and very slow HPC leakage, which led to a slow increase in permeability. Films with grade L and SL released most of their HPC, yet the permeability of the L film was three times higher due to greater pore connectivity. It was concluded that the phase-separated microstructure, the level of pore percolation and the leakage rate of HPC will be affected by the choice of HPC Mw grade used in the film and this will in turn have strong impact on the film permeability.
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| 3. |
- Bjureberg, Johan, et al.
(författare)
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Effect of Internet-Delivered Emotion Regulation Individual Therapy for Adolescents With Nonsuicidal Self-Injury Disorder : A Randomized Clinical Trial
- 2023
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Ingår i: JAMA Network Open. - : American Medical Association (AMA). - 2574-3805. ; 6:7
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE: Nonsuicidal self-injury is prevalent in adolescence and associated with adverse clinical outcomes. Effective interventions that are brief, transportable, and scalable are lacking.OBJECTIVE: To test the hypotheses that an internet-delivered emotion regulation individual therapy for adolescents delivered adjunctive to treatment as usual is superior to treatment as usual only in reducing nonsuicidal self-injury and that improvements in emotion regulation mediate these treatment effects.DESIGN, SETTING, AND PARTICIPANTS: This 3-site, single-masked, randomized superiority trial enrolled participants from November 20, 2017, to April 9, 2020. Eligible participants were aged between 13 and 17 years and met diagnostic criteria for nonsuicidal self-injury disorder; they were enrolled as a mixed cohort of consecutive patients and volunteers. Parents participated in parallel to their children. The primary end point was at 1 month after treatment. Participants were followed up at 3 months posttreatment. Data collection ended in January 2021.INTERVENTIONS: Twelve weeks of therapist-guided, internet-delivered emotion regulation individual therapy delivered adjunctive to treatment as usual vs treatment as usual only.MAIN OUTCOMES AND MEASURES: Primary outcome was the youth version of the Deliberate Self-harm Inventory, both self-reported by participants prior to treatment, once every week during treatment, and for 4 weeks posttreatment, and clinician-rated by masked assessors prior to treatment and at 1 and 3 months posttreatment.RESULTS: A total of 166 adolescents (mean [SD] age, 15.0 [1.2] years; 154 [92.8%] female) were randomized to internet-delivered emotion regulation therapy plus treatment as usual (84 participants) or treatment as usual only (82 participants). The experimental intervention was superior to the control condition in reducing clinician-rated nonsuicidal self-injury (82% vs 47% reduction; incidence rate ratio, 0.34; 95% CI, 0.20-0.57) from pretreatment to 1-month posttreatment. These results were maintained at 3-month posttreatment. Improvements in emotion dysregulation mediated improvements in self-injury during treatment.CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, a 12-week, therapist-guided, internet-delivered emotion regulation therapy delivered adjunctive to treatment as usual was efficacious in reducing self-injury, and mediation analysis supported the theorized role of emotion regulation as the mechanism of change in this treatment. This treatment may increase availability of evidence-based psychological treatments for adolescents with nonsuicidal self-injury.TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03353961.
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| 4. |
- Dubois, Hanna, et al.
(författare)
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Exploring differences in patient participation in simulated emergency cases in co-located and distributed rural emergency teams : an observational study with a randomized cross-over design
- 2024
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Ingår i: BMC Emergency Medicine. - : BioMed Central (BMC). - 1471-227X. ; 24:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: In northern rural Sweden, telemedicine is used to improve access to healthcare and to provide patient-centered care. In emergency care during on-call hours, video-conference systems are used to connect the physicians to the rest of the team – creating ‘distributed teams’. Patient participation is a core competency for healthcare professionals. Knowledge about how distributed teamwork affects patient participation is missing. The aim was to investigate if and how teamwork affecting patient participation, as well as clinicians’ perceptions regarding shared decision-making differ between co-located and distributed emergency teams.Methods: In an observational study with a randomized cross-over design, healthcare professionals (n = 51) participated in authentic teams (n = 17) in two scripted simulated emergency scenarios with a standardized patient: one as a co-located team and the other as a distributed team. Team performances were filmed and observed by independent raters using the PIC-ET tool to rate patient participation behavior. The participants individually filled out the Dyadic OPTION questionnaire after the respective scenarios to measure perceptions of shared decision-making. Scores in both instruments were translated to percentage of a maximum score. The observational data between the two settings were compared using linear mixed-effects regression models and the self-reported questionnaire data were compared using one-way ANOVA. Neither the participants nor the observers were blinded to the allocations.Results: A significant difference in observer rated overall patient participation behavior was found, mean 51.1 (± 11.5) % for the co-located teams vs 44.7 (± 8.6) % for the distributed teams (p = 0.02). In the PIC-ET tool category ‘Sharing power’, the scores decreased from 14.4 (± 12.4) % in the co-located teams to 2 (± 4.4) % in the distributed teams (p = 0.001). Co-located teams scored in mean 60.5% (± 14.4) when self-assessing shared decision-making, vs 55.8% (± 15.1) in the distributed teams (p = 0.03).Conclusions: Team behavior enabling patient participation was found decreased in distributed teams, especially regarding sharing power with the patient. This finding was also mirrored in the self-assessments of the healthcare professionals. This study highlights the risk of an increased power asymmetry between patients and distributed emergency teams and can serve as a basis for further research, education, and quality improvement.
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| 5. |
- Gahrton, Caroline, et al.
(författare)
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Mortality among amphetamine users with hepatitis C virus infection : A nationwide study
- 2021
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Ingår i: PLOS ONE. - : PLOS. - 1932-6203. ; 16:6
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: To investigate liver-related and all-cause mortality among amphetamine users with hepatitis C virus (HCV) infection and compare this with opioid users with HCV infection and the uninfected general population.METHODS: In this national register study of mortality in persons notified with HCV infection 1990-2015 and a substance-related diagnosis in Sweden, amphetamine users (n = 6,509) were compared with opioid users (n = 5,739) and a matched comparison group without HCV infection/substance use (n = 152,086).RESULTS: Amphetamine users were observed for 91,000 years and 30.1% deceased. Crude liver-related mortality was 1.8 times higher in amphetamine users than opioid users (crude mortality rate ratio 1.78, 95% CI 1.45-2.19), but there was no significant difference when adjusting for age and other defined risk factors. An alcohol-related diagnosis was associated with liver-related death and was more common among amphetamine users. Crude and adjusted liver-related mortality was 39.4 and 5.8 times higher, respectively, compared with the uninfected group. All-cause mortality was lower than in opioid users (adjusted mortality rate ratio 0.78, 95% CI 0.73-0.84), but high compared with the uninfected group. External causes of death dominated in younger ages whereas liver-related death was more common among older individuals.CONCLUSIONS: This national register study presents a higher crude risk of liver-related death among HCV-infected amphetamine users compared with opioid users or the uninfected general population. The higher risk of liver-related death compared with opioid users may be explained by lower competing death risk and higher alcohol consumption. Treatment of HCV infection and alcohol use disorders are needed to reduce the high liver-related mortality.
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| 6. |
- Häbel, Henrike, 1987, et al.
(författare)
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A three-dimensional anisotropic point process characterization for pharmaceutical coatings
- 2017
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Ingår i: Spatial Statistics. - : Elsevier BV. - 2211-6753. ; 22:2, s. 306-320
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Tidskriftsartikel (refereegranskat)abstract
- © 2017 Elsevier B.V. Spatial characterization and modeling of the structure of a material may provide valuable knowledge on its properties and function. Especially, for a drug formulation coated with a polymer film, understanding the relationship between pore structure and drug release properties is important to optimize the coating film design. Here, we use methods from image analysis and spatial statistics to characterize and model the pore structure in pharmaceutical coatings. More precisely, we use and develop point process theory to characterize the branching structure of a polymer blended film with data from confocal laser scanning microscopy. Point patterns, extracted by identifying branching points of pore channels, are both inhomogeneous and anisotropic. Therefore, we introduce a directional version of the inhomogeneous K-function to study the anisotropy and then suggest two alternative ways to model the anisotropic three-dimensional structure. First, we apply a linear transformation to the data such that it appears isotropic and subsequently fit isotropic inhomogeneous Strauss or Lennard-Jones models to the transformed pattern. Second, we include the anisotropy directly in a Lennard-Jones and a more flexible step-function model with anisotropic pair-potential functions. The methods presented will be useful for anisotropic inhomogeneous point patterns in general and for characterizing porous material in particular.
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| 7. |
- Häbel, Henrike, 1987
(författare)
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Characterization of Micro-Structures in Materials
- 2015
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- On developing the next generation sustainable soft materials, it is often crucial to understand and control their properties and function. Whereas a characterization of three-dimensional data is desirable in corresponding studies, often two-dimensional data are less time consuming to obtain. Consequently, characterizing the three-dimensional micro-structure of a material from two-dimensional data would enable efficient screening of its properties. In this work, the challenge of characterizing two different materials from two-dimensional images obtained by scanning (transmission) electron microscopy is overcome by using tools from image analysis and spatial statistics. The two different materials are a colloidal nanoparticle gel and a polymer blended film. The characterization of the micro-structures in the materials is conducted in two main steps. First, the microscopy images are processed in order to identify the objects of interest. Second, the structures are characterized according to the objects of interest. In particular, the spatial arrangement of nanoparticles is evaluated by summary functions from spatial statistics. One such function based on the size of a cluster of particles has been developed in this project. For the pore space analysis of a polymer blended film, tools from image analysis are applied to measure and compare the shapes of pores in a statistical analysis. The results obtained in this work, may be useful for reconstructions of the micro-structure in materials in three dimensions. Such reconstructions can be used to analyze materials, which may not yet have even been synthesized, in simulation studies without experiments involving valuable resources. In that way, new sustainable high quality products may be developed.
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| 8. |
- Häbel, Henrike, 1987, et al.
(författare)
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Characterization of pore structure of polymer blended films used for controlled drug release
- 2016
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Ingår i: Journal of Controlled Release. - : Elsevier BV. - 0168-3659 .- 1873-4995. ; 222, s. 151-158
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Tidskriftsartikel (refereegranskat)abstract
- The characterization of the pore structure in pharmaceutical coatings is crucial for understanding and controlling mass transport properties and function in controlled drug release. Since the drug release rate can be associated with the film permeability, the effect of the pore structure on the permeability is important to study. In this paper, a new approach for characterizing the pore structure in polymer blended films was developed based on an image processing procedure for given two-dimensional scanning electron microscopy images of film cross-sections. The focus was on different measures for characterizing the complexity of the shape of a pore. The pore characterization developed was applied to ethyl cellulose (EC) and hydroxypropyl cellulose (HPC) blended films, often used as pharmaceutical coatings, where HPC acts as the pore former. It was studied how two different HPC viscosity grades influence the pore structure and, hence, mass transport through the respective films. The film with higher HPC viscosity grade had been observed to be more permeable than the other in a previous study; however, experiments had failed to show a difference between their pore structures. By instead characterizing the pore structures using tools from image analysis, statistically significant differences in pore area fraction and pore shape were identified. More specifically, it was found that the more permeable film with higher HPC viscosity grade seemed to have more extended and complex pore shapes than the film with lower HPC viscosity grade. This result indicates a greater degree of connectivity in the film with higher permeability and statistically confirms hypotheses on permeability from related experimental studies.
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| 9. |
- Häbel, Henrike, 1987, et al.
(författare)
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Colloidal particle aggregation in three dimensions
- 2019
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Ingår i: Journal of Microscopy. - : Wiley. - 0022-2720 .- 1365-2818. ; 275:3, s. 149-158
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Tidskriftsartikel (refereegranskat)abstract
- Colloidal systems are of importance not only for everyday products, but also for the development of new advanced materials. In many applications, it is crucial to understand and control colloidal interaction. In this paper, we study colloidal particle aggregation of silica nanoparticles, where the data are given in a three-dimensional micrograph obtained by high-angle annular dark field scanning transmission electron microscopy tomography. We investigate whether dynamic models for particle aggregation, namely the diffusion limited cluster aggregation and the reaction limited cluster aggregation models, can be used to construct structures present in the scanning transmission electron microscopy data. We compare the experimentally obtained silica aggregate to the simulated postaggregated structures obtained by the dynamic models. In addition, we fit static Gibbs point process models, which are commonly used models for point patterns with interactions, to the silica data. We were able to simulate structures similar to the silica structures by using Gibbs point process models. By fitting Gibbs models to the simulated cluster aggregation patterns, we saw that a smaller probability of aggregation would be needed to construct structures similar to the observed silica particle structure.
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| 10. |
- Häbel, Henrike, 1987
(författare)
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From experiments with images to 3D models
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- For developing the next generation sustainable materials, it is often crucial to understand and control their properties and function. This work presents cross-disciplinary research starting with experimentally fabricated porous soft biomaterials and images of their micro-structure obtained by electron or laser microscopy. It is investigated how much information on the three-dimensional material structure can be extracted from two-dimensional images and how conclusions compare to three-dimensional image analysis. Based on the image data, spatial statistical models are constructed and fitted to two different materials: a colloidal nanoparticle gel and a porous polymer blended film. Colloidal systems are everywhere in our everyday life and of high interest for the development of new advanced materials. Polymer films are popular for pharmaceutical coatings which control the release of a drug to obtain important therapeutic benefits. Besides presenting image analysis routines, three-dimensional finite Gibbs point processes with inhomogeneous and anisotropic pair-potential functions are introduced. Observed point patterns are formed by silica particle positions or pore branching points located at intersections of at least three pore channels. Due to physical chemical forces between particles and polymers, it is assumed that the points interact with each other. The pairwise interaction is described in the pair-potential function of a Gibbs process. In this way, there is a link between static Gibbs point process models and dynamic physical chemical processes like colloidal particle aggregation and polymer phase separation. Furthermore, a new spatial statistical summary function is suggested for the cluster size analysis on different length scales in aggregated structures. This function is a useful tool for comparing two regimes for particle aggregation resulting in different size and shape distributions of particle clusters. More precisely, it is used to study the diffusion limited and the reaction limited cluster aggregation. The methods introduced in this work can be applied to point processes in general and are important contributions to the point process literature. The results are useful for setting up a virtual design framework for the study of properties of various materials, which may not yet have even been synthesized, in simulation studies instead of experiments involving valuable resources.
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| 11. |
- Häbel, Henrike, 1987, et al.
(författare)
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From static micrographs to particle aggregation dynamics in three dimensions
- 2016
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Ingår i: Journal of Microscopy. - : Wiley. - 1365-2818 .- 0022-2720. ; 262:1, s. 102-111
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Tidskriftsartikel (refereegranskat)abstract
- Studies on colloidal aggregation have brought forth theories on stability of colloidal gels and models for aggregation dynamics. Still, a complete link between developed frameworks and obtained laboratory observations has to be found. In this work, aggregates of silica nanoparticles (20 nm) are studied using diffusion limited cluster aggregation (DLCA) and reaction limited cluster aggregation (RLCA) models. These processes are driven by the probability of particles to aggregate upon collision. This probability of aggregation is one in the DLCA and close to zero in the RLCA process. We show how to study the probability of aggregation from static micrographs on the example of a silica nanoparticle gel at 9 wt%. The analysis includes common summary functions from spatial statistics, namely the empty space function and Ripley's K-function, as well as two newly developed summary functions for cluster analysis based on graph theory. One of the new cluster analysis functions is related to the clustering coefficient in communication networks and the other to the size of a cluster. All four topological summary statistics are used to quantitatively compare in plots and in a least-square approach experimental data to cluster aggregation simulations with decreasing probabilities of aggregation. We study scanning transmission electron micrographs and utilize the intensity - mass thickness relation present in such images to create comparable micrographs from three-dimensional simulations. Finally, a characterization of colloidal silica aggregates and simulated structures is obtained, which allows for an evaluation of the cluster aggregation process for different aggregation scenarios. As a result, we find that the RLCA process fits the experimental data better than the DLCA process.
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| 12. |
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| 13. |
- Karimi, Mahssa, et al.
(författare)
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A sleep apnea related risk of vehicle accident is reduced by CPAP - Swedish traffic accident data acquisition (STRADA) registry
- 2014
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Ingår i: 22nd Congress of the European Sleep Research Society, 16–20 September 2014, Tallinn, Estonia. Journal of Sleep Research. - : Wiley. - 0962-1105 .- 1365-2869. ; 23:Suppl 1, s. 67-67
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Obstructive sleep apnea (OSA) is associated with excessive daytime sleepiness (EDS) and two to seven times increased risk of motor vehicle accidents (MVAs) compared with the general population. The MVA rate in patients with suspected OSA, clinical features and the effect of treatment on risk prediction was investigated. Methods: Clinical sleep laboratory patients were cross-analyzed with a matched control group from the general population. The 10-year incidence of MVA among patients (n = 1478, 70.4% males, mean age 54 (13) years) and accidents (n = 21118) in the general population was analyzed. Risk factors associated with MVA risk were determined in patients with OSA. Results: Observed accidents among patients (n = 74) were compared with the expected number (n = 29.91, risk ratio 2.47, P < 0.001) predicted from the control population. Observed MVAs were more prevalent among younger (18–44 years) patiens but estimated OSA related excess accident risk was most prominent in elderly (65–80 years, risk ratio 3.5) drivers. Risk factors within the OSA patient cohort (high traffic exposure≥15 000 km/year, Epworth Sleepiness Score ≥16, habitual sleep time ≤5 h/night and use of hypnotics) were associated with increased accident risk (odds ratio 1.2, 2.1, 2.7 and 2.1, respectively, all P ≤ 0.03. Compliance with CPAP (≥4 h/night), was associated with a reduction of MVA frequency (7.6 to 2.5 accidents/1000 drivers/year). Conclusions: The motor vehicle accident risk in this large cohort of unselected sleep apnea patients suggests a need for accurate tools to identify individuals at risk. Conventional metrics of sleep apnea severity (e.g. apnea-hypopnea-index) failed to identify patients at risk.
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| 14. |
- Krakowski, Isabelle, et al.
(författare)
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Association of metformin use and survival in patients with cutaneous melanoma and diabetes
- 2023
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Ingår i: The British journal of dermatology. - : Oxford University Press (OUP). - 1365-2133 .- 0007-0963. ; 188:1, s. 32-40
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Metformin use has been associated with improved survival in patients with different types of cancer, but research regarding the effect of metformin on cutaneous melanoma (CM) survival is sparse and inconclusive.OBJECTIVES: To investigate the association between metformin use and survival among patients with CM and diabetes.METHODS: All adult patients with a primary invasive CM between 2007 and 2014 were identified in the Swedish Melanoma Registry and followed until death, or end of follow-up on 31 December 2017 in this population-based cohort study. Patients with both CM and type 2 diabetes mellitus were assessed further. Overall survival (OS) and melanoma-specific survival (MSS) were the primary endpoints. Cox proportional hazard models estimating crude and adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were used comparing peridiagnostic use vs. nonuse of metformin. Dose response was evaluated based on defined daily doses.RESULTS: Among a total of 23 507 patients, 1162 patients with CM and type 2 diabetes mellitus were included in the final cohort, with a median follow-up time of 4.1 years (interquartile range 2.4-6.1). Peridiagnostic metformin use was associated with a significantly decreased risk of death by any cause (HR 0.68, 95% CI 0.57-0.81). Cumulative pre- and postdiagnostic metformin use was also associated with improved OS: the HR for prediagnostic use was 0.90 (95% CI 0.86-0.95) for every 6 months of use and the HR for postdiagnostic use ranged from 0.98 (95% CI 0.97-0.98) for 0-6 months to 0.59 (0.49-0.70) for 24-30 months of use. No association was found for metformin use and MSS.CONCLUSIONS: Metformin use was associated with improved OS in patients with CM and diabetes regardless of timing (pre-, post- or peridiagnostic use) and followed a dose-response pattern. However, further research regarding the underlying mechanisms is warranted.
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| 15. |
- Lidbeck, Cecilia, et al.
(författare)
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Motor Development in Children with Cerebral Palsy in Sweden : A Population-Based Longitudinal Register Study
- 2023
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Ingår i: Children. - : MDPI. - 2227-9067. ; 10:12
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Tidskriftsartikel (refereegranskat)abstract
- The aim was to explore longitudinal motor development in children with cerebral palsy (CP) in Sweden with respect to the Gross Motor Function Classification System (GMFCS). In this national CP registry-based study, 2138 children aged 0.5-19 years participated (42% girls). The distribution with respect to GMFCS was I: 49%, II: 16%, III: 10%, IV: 14%, and V: 11%. In total, 5538 assessments (mean 2.7, min-max: 1-9) with the Gross Motor Function Measure-66 were included. Data were analysed using non-linear mixed-effects regression models, and the Stable Limit Model was selected to fit data. Five distinct curves of predicted gross motor development with respect to GMFCS levels were obtained. The achieved motor development was maintained over time. The estimated average GMFM-66 limit and the average age when 90% of the expected limits were reached were at GMFCS I: 88 at age 4.5; GMFCS II: 71 at age 4.2; GMFCS III: 54 at age 3.1; GMFCS IV: 38 at age 2.6, and at GMFCS V: 18 at age 0.9. In conclusion, this is the first national population-based study following motor development in CP. Five distinct curves reported in previous controlled research studies were confirmed. Our study adds knowledge about motor development captured in children's everyday context.
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| 16. |
- Littmann, Karin, et al.
(författare)
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Plasma lipoprotein(a) measured in the routine clinical care is associated to atherosclerotic cardiovascular disease during a 14-year follow-up.
- 2021
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Ingår i: European Journal of Preventive Cardiology. - : Oxford University Press. - 2047-4873 .- 2047-4881. ; 28:18, s. 2038-2047
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: To investigate plasma lipoprotein(a) [Lp(a)] levels measured in routine clinical care and their association with mortality and cardiovascular disease.METHODS AND RESULTS: This retrospective registry-based observational cohort study includes all individuals with plasma Lp(a) results measured at the Karolinska University Laboratory 2003-17. Outcome data were captured in national outcome registries. Levels of Lp(a) expressed in mass or molar units were examined separately. In adjusted Cox regression models, association between deciles of plasma Lp(a) concentrations, mortality, and cardiovascular outcomes were assessed. A total of 23 398 individuals [52% females, mean (standard deviation) age 55.5 (17.2) years, median Lp(a) levels 17 mg/dL or 19.5 nmol/L] were included. Individuals with an Lp(a) level >90th decile (>90 mg/dL or >180 nmol/L) had hazard ratios (95% confidence interval) of 1.25 (1.05-1.50) for major adverse cardiovascular events (P = 0.013), 1.37 (1.14-1.64) for atherosclerotic cardiovascular disease (P = 0.001), and 1.62 (1.28-2.05) for coronary artery disease (P ≤ 0.001), compared to individuals with Lp(a) ≤50th decile. No association between Lp(a) and mortality, peripheral artery disease, or ischaemic stroke was observed.CONCLUSION: High Lp(a) levels are associated with adverse cardiovascular disease outcomes also in individuals with Lp(a) measured in routine clinical care. This supports the 2019 ESC/EAS recommendation to measure Lp(a) at least once during lifetime to assess cardiovascular risk and implies the need for intensive preventive therapy in patients with elevated Lp(a).
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| 17. |
- Mattfeldt, T., et al.
(författare)
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Block bootstrap methods for the estimation of the intensity of a spatial point process with confidence bounds
- 2013
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Ingår i: Journal of Microscopy. - : Wiley. - 0022-2720 .- 1365-2818. ; 251:1, s. 84-98
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Tidskriftsartikel (refereegranskat)abstract
- This paper deals with the estimation of the intensity of a planar point process on the basis of a single point pattern, observed in a rectangular window. If the model assumptions of stationarity and isotropy hold, the method of block bootstrapping can be used to estimate the intensity of the process with confidence bounds. The results of two variants of block bootstrapping are compared with a parametric approximation based on the assumption of a Gaussian distribution of the numbers of points in deterministic subwindows of the original pattern. The studies were performed on patterns obtained by simulation of well-known point process models (Poisson process, two Matern cluster processes, Matern hardcore process, Strauss hardcore process). They were also performed on real histopathological data (point patterns of capillary profiles of 12 cases of prostatic cancer). The methods are presented as worked examples on two cases, where we illustrate their use as a check on stationarity (homogeneity) of a point process with respect to different fields of vision. The paper concludes with various methodological discussions and suggests possible extensions of the block bootstrap approach to other fields of spatial statistics.
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| 18. |
- Nordin, Matias, 1981, et al.
(författare)
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Estimation of mass thickness response of embedded aggregated silica nanospheres from high angle annular dark-field scanning transmission electron micrographs
- 2014
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Ingår i: Journal of Microscopy. - : Wiley. - 0022-2720 .- 1365-2818. ; 253:2, s. 166-170
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Tidskriftsartikel (refereegranskat)abstract
- In this study, we investigate the functional behaviour of the intensity in high-angle annular dark field scanning transmission electron micrograph images. The model material is a silica particle (20 nm) gel at 5 wt%. By assuming that the intensity response is monotonically increasing with increasing mass thickness of silica, an estimate of the functional form is calculated using a maximum likelihood approach. We conclude that a linear functional form of the intensity provides a fair estimate but that a power function is significantly better for estimating the amount of silica in the z-direction. The work adds to the development of quantifying material properties from electron micrographs, especially in the field of tomography methods and three-dimensional quantitative structural characterization from a scanning transmission electron micrograph. It also provides means for direct three-dimensional quantitative structural characterization from a scanning transmission electron micrograph.
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| 19. |
- Ohm, Joel, et al.
(författare)
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Socioeconomic Disparities and Mediators for Recurrent Atherosclerotic Cardiovascular Disease Events After a First Myocardial Infarction
- 2023
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Ingår i: Circulation. - : Lippincott Williams & Wilkins. - 0009-7322 .- 1524-4539. ; 148:3, s. 256-267
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:Low socioeconomic status is associated with worse secondary prevention use and prognosis after myocardial infarction (MI). Actions for health equity improvements warrant identification of risk mediators. Therefore, we assessed mediators of the association between socioeconomic status and first recurrent atherosclerotic cardiovascular disease event (rASCVD) after MI.METHODS:In this cohort study on 1-year survivors of first-ever MI with Swedish universal health coverage ages 18 to 76 years, individual-level data from SWEDEHEART (Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies) and linked national registries was collected from 2006 through 2020. Exposure was socioeconomic status by disposable income quintile (principal proxy), educational level, and marital status. The primary outcome was rASCVD and secondary outcomes were cardiovascular and all-cause mortality. We initially assessed the incremental attenuation of hazard ratios with 95% CIs in sequential multivariable models adding groups of potential mediators (ie, previous risk factors, acute presentation and infarct severity, initial therapies, and secondary prevention). Thereafter, the proportion of excess rASCVD associated with a low income mediated through nonparticipation in cardiac rehabilitation, suboptimal statin management, a cardiometabolic risk profile, persistent smoking, and blood pressure above target after MI were calculated using causal mediation analysis.RESULTS:Among 68 775 participants (73.8% men), 7064 rASCVD occurred during a mean 5.7-year follow-up. Income, adjusted for age, sex, and calendar year, was associated with rASCVD (hazard ratio, 1.63 [95% CI, 1.51-1.76] in the lowest versus highest income quintile). Risk attenuated most by adjustment for previous risk factors and by adding secondary prevention variables for a final model (hazard ratio, 1.38 [95% CI, 1.26-1.51]) in the lowest versus highest income quintile. The proportions of the excess 15-year rASCVD risk in the lowest income quintile mediated through nonparticipation in cardiac rehabilitation, cardiometabolic risk profile, persistent smoking, and poor blood pressure control were 3.3% (95% CI 2.1-4.8), 3.9% (95% CI, 2.9-5.5), 15.2% (95% 9.1-25.7), and 1.0% (95% CI 0.6-1.5), respectively. Risk mediation through optimal statin management was negligible.CONCLUSIONS:Nonparticipation in cardiac rehabilitation, a cardiometabolic risk profile, and persistent smoking mediate income-dependent prognosis after MI. In the absence of randomized trials, this causal inference approach may guide decisions to improve health equity.
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| 20. |
- Sundén-Cullberg, Jonas, et al.
(författare)
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Anakinra or tocilizumab in patients admitted to hospital with severe covid-19 at high risk of deterioration (IMMCoVA): A randomized, controlled, open-label trial
- 2023
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 18:12
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Tidskriftsartikel (refereegranskat)abstract
- Background: Anakinra and tocilizumab are used for severe Covid-19, but only one previous randomized controlled trial (RCT) has studied both. We performed a multi-center RCT comparing anakinra or tocilizumab versus usual care (UC) for adults at high risk of deterioration.Methods: The study was conducted June 2020 to March 2021. Eligibility required ≥ 5 liters/minute of Oxygen to maintain peripheral oxygen saturation at ≥ 93%, CRP > 70 mg/L, ferritin > 500 μg/L and at least two points where one point was awarded for lymphocytes < 1x 109/L; D-dimer ≥ 0.5 mg/L and; lactate dehydrogenase ≥ 8 microkatal/L. Patients were randomly assigned 1:1:1 to receive either a single dose of tocilizumab (8 mg/kg) or anakinra 100 mg IV QID for seven days or UC alone. The primary outcome was time to recovery.Results: Recruitment was ended prematurely when tocilizumab became part of usual care. Out of a planned 195 patients, 77 had been randomized, 27 to UC, 28 to anakinra and 22 to tocilizumab. Median time to recovery was 15, 15 and 11 days. Rate ratio for recovery for UC vs anakinra was 0.91, 0.47 to 1.78, 95% [CI], p = 0.8 and for UC vs tocilizumab 1.13, 0.55 to 2.30; p = 0.7. There were non-significant trends favoring tocilizumab (and to limited degree anakinra) vs UC for some secondary outcomes. Safety profiles did not differ significantly.Conclusion: Premature closure of trial precludes firm conclusions. Anakinra or tocilizumab did not significantly shorten time to clinical recovery compared to usual care. (IMMCoVA, NCT04412291, EudraCT: 2020-00174824).
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| 21. |
- Tan, Edwin C. K., et al.
(författare)
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Validating a model for medication-related dental outcomes in older people
- 2022
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Ingår i: Oral Diseases. - : Wiley. - 1354-523X .- 1601-0825. ; 28:6, s. 1697-1704
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To externally validate a model for medication-related dental outcomes in (a) a general older population with dementia and (b) a matched population without dementia.Subjects and Methods: This validation study used population-based data from seven Swedish national registers (2008–2017). Individuals aged 60+ with dementia were matched to those without dementia on age, gender, and county of residence at the date of diagnosis (index date). The exposure was continuous use of xerogenic medications during the 3-year period before index date. The primary outcome was the number of tooth extraction and restorative procedures within 3 years after index date.Results: A total of 334,220 individuals were included in the final sample. In the dementia cohort, the use of urological drugs (incidence rate ratio [IRR] 1.08, 95% CI 1.03–1.13), respiratory medicines (IRR 1.10, 95% CI 1.04–1.17), and proton-pump inhibitors (IRR 1.09, 95% CI 1.05–1.13) was associated with the primary outcome. In the non-dementia cohort, respiratory medicines (IRR 1.03, CI 1.00–1.05), proton-pump inhibitors (IRR 1.06, CI 1.04–1.08), opioids (IRR 1.05, CI 1.03–1.07), and antidepressants (IRR 1.06, CI 1.04–1.08) were associated with the primary outcome.Conclusions: Although there were differences in prescription patterns, the model performed similarly in both those with and without dementia.
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| 22. |
- Tan, Edwin C. K., et al.
(författare)
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Xerogenic Medications as a Predictor for Dental Health Intervention in People with Dementia
- 2020
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Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 75:4, s. 1263-1271
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Tidskriftsartikel (refereegranskat)abstract
- Background: Older adults with dementia often have poor oral health. Chronic use of xerogenic medications may contribute to adverse dental outcomes.Objective: To investigate the impact of xerogenic medication classes on the predicted risk for dental interventions in people with dementia.Methods: Thiswas a population-based cohort study involving 30,955 individuals registered in the Swedish Dementia Registry (SveDem) from 2008 to 2015. Data were linked with other national registers. The exposure was xerogenic medication classes used in the three years prior to dementia diagnosis (baseline). The primary outcome was the composite of number of tooth extractions and dental restorations over the three-year follow-up period. Secondary outcomes included the number of tooth extractions and number of dental restorations. Poisson regression models were used to estimate the association between the exposure and outcomes. Analyses were adjusted for age, gender, Mini-Mental State Examination, living arrangement, dementia disorder, average number of medications, Charlson’s comorbidity index, number of dental visits, and number of teeth.Results: After adjusting for potential covariates, the use of urological drugs (incidence rate ratio [IRR] 1.16, 95% CI 1.04–1.28), proton pump inhibitors (IRR 1.13, 95% CI 1.04–1.23), and opioids (IRR 1.19, 95% CI 1.06–1.34) were significantly associated with the primary composite outcome.Conclusion: The use of specific classes of xerogenic medications was associated with an increased risk for tooth extractions and restorations in people with dementia. The risks and benefits of xerogenic medications, in the context of oral health, should be carefully assessed in this vulnerable population.
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| 23. |
- Tollemar, Victor, et al.
(författare)
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Immunohistopathology of oral mucosal chronic graft-versus-host disease severity and duration
- 2023
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Ingår i: Oral Diseases. - : John Wiley & Sons. - 1354-523X .- 1601-0825. ; 29:8, s. 3346-3359
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Tidskriftsartikel (refereegranskat)abstract
- Objective Chronic graft-versus-host disease (cGVHD) is the main cause of late non-relapse mortality following hematopoietic cell transplantation. Oral mucosal (om-) cGVHD is common, but diagnosis and assessment rely on clinical interpretation and patient-reported symptoms. We investigated immunohistopathological profiles with respect to om-cGVHD severity disease duration. Material and methods Ninety-four transplant patients and 15 healthy controls (n = 212 biopsies) were investigated by quantitative immunohistochemistry for T cells (CD4, CD8, and CD5), B cells (CD19 and CD20), macrophages (CD68), and Langerhans cells (CD1a). Results We found significant increases in T (CD4, CD8) and monocytic (CD68) cells in om-cGVHD, and a notable absence of B (CD19 and CD20) cells. Histopathological activity correlated with increased CD4, CD8 and CD68. However, CD4 was associated with mild om-cGVHD, whereas CD8 and CD68 were found to be elevated in severe om-cGVHD. CD8 and CD68 levels were raised at disease onset, but during late phase, the predominant CD68 population was accompanied by CD4. Conclusion Oral cGVHD is a heterogenous clinical disorder, but our knowledge of the underlying biology remains limited. We highlight the importance of CD4, CD8 and CD68 immune profiling, together with histological grading for the staging of oral cGVHD, to broaden our understanding of the biology and individual disease course.
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| 24. |
- Wodaje, Tigist, et al.
(författare)
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Higher prevalence of coronary microvascular dysfunction in asymptomatic individuals with high levels of lipoprotein(a) with and without heterozygous familial hypercholesterolaemia
- 2024
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Ingår i: Atherosclerosis. - 0021-9150 .- 1879-1484. ; 389
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Tidskriftsartikel (refereegranskat)abstract
- Background and aims: Microvascular dysfunction underlies many cardiovascular disease conditions; little is known regarding its presence in individuals with high levels of lipoprotein(a) [Lp(a)]. The aim of the present study was to determine the frequency of microvascular dysfunction among such subjects with and without concomitant familial hypercholesterolemia (FH). Methods: Four groups of asymptomatic individuals aged 30–59 years, without manifest cardiovascular disease, were recruited (n = 30 per group): controls with Lp(a) < 30 nmol/L, mutation-confirmed FH with Lp(a) < 30 nmol/L, or >125 nmol/L, and individuals with isolated Lp(a) > 125 nmol/L. Participants underwent evaluation of myocardial microvascular function by measuring coronary flow reserve (CFR) using transthoracic Doppler echocardiography, and of peripheral microvascular endothelial function by peripheral arterial tonometry. Results: The groups were balanced in age, sex, and body mass index. Each of the three dyslipoproteinaemic groups had a greater proportion of individuals with impaired coronary flow reserve, 30%, compared to 6.7% of controls (p = 0.014). The median CFR levels did not differ significantly between the four groups, however. Cholesterol-lowering treatment time was longer in the individuals with normal than in those with impaired CFR in the FH + Lp(a) > 125 group (p = 0.023), but not in the group with FH + Lp(a) < 30 (p = 0.468). There was no difference in peripheral endothelial function between the groups. Conclusions: Coronary microvascular dysfunction is more prevalent in asymptomatic individuals with isolated Lp(a) elevation and in heterozygous FH both with and without high Lp(a) compared to healthy controls. Cholesterol-lowering treatment could potentially prevent the development of microvascular dysfunction.
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| 25. |
- Åkerstedt, Torbjörn, et al.
(författare)
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Acute and cumulative effects of scheduling on aircrew fatigue in ultra-short-haul operations
- 2021
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Ingår i: Journal of Sleep Research. - : Wiley. - 0962-1105 .- 1365-2869. ; 30:5
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Tidskriftsartikel (refereegranskat)abstract
- Aircrew fatigue constitutes a safety hazard in aviation, which authorities attempt to mitigate through flight time limitations. Some gaps in knowledge exist, however. The purpose of the present study was to investigate the associations of schedule characteristics with fatigue and amount of sleep in the acute 24-h window, and as cumulative effects across the 7-day work period. One hundred and six aircrew (14% cabin crew) participated. They rated fatigue on the Karolinska Sleepiness Scale (KSS) three times per flight day for four 7-day work periods, with up to 7 days off between work periods. Mixed model regression was applied to the data. In the multivariable model, more sleep was associated with lower fatigue (p = .000)), corresponding to 0.26 KSS units less per hour of sleep. Very early, early and late duty types, as well as duty time, were associated with higher fatigue. For the 7-day work period, accumulation of very early duties and longer duty time were associated with increased fatigue, and more accumulated sleep was associated with lower fatigue in the adjusted model (0.08 KSS units per hour of sleep) (p = .000). Accumulated duty time was not significant when analysed as a single variable, but became so after adjustment for sleep. The results suggest that sleep, duty time and early starts are important predictors of fatigue in the 24-h window and that the number of very early starts and short sleep have cumulative effects on fatigue across a 7-day work period.
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