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1.
  • Ahlm, Kristin, et al. (author)
  • Suicidal drowning deaths in northern Sweden 1992-2009 : the role of mental disorder and intoxication
  • 2015
  • In: Journal of Forensic and Legal Medicine. - : Elsevier. - 1752-928X .- 1878-7487. ; 34, s. 168-172
  • Journal article (peer-reviewed)abstract
    • Suicides by drowning have received limited attention by researchers. A recent finding that almost onethird of all drowning deaths in Sweden were classified as suicide instigated this study. We identified 129 cases of suicide by drowning in Northern Sweden and analyzed the circumstances and the psychiatric history prior to the suicide. Information was obtained from autopsy, police and medical records, as well as from the National Inpatient Register. One-third of the suicide victims had previously attempted suicide and half of the victims had been hospitalized due to mental health problems. One-third of these had left the hospital less than one week before the suicide. Alcohol and psychoactive drugs were present in 16% and 62% of the cases, respectively. A history of mental disorder and previous suicide attempt (s), especially by drowning, is an ominous combination necessitating efficient clinical identification, treatment and follow-up if a complete suicide is to be prevented.
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4.
  • Almgren, Magnus, 1972, et al. (author)
  • A Comparison of Alternative Audit Sources for Web Server Attack Detection
  • 2007
  • In: The 12th Nordic Workshop on Secure IT-systems.
  • Conference paper (peer-reviewed)abstract
    • Most intrusion detection systems available today are usinga single audit source for detecting all attacks, eventhough attacks have distinct manifestations in differentparts of the system. In this paper we carry out a theoretical investigation of the role of the audit source for the detection capability of the intrusion detection system (IDS). Concentrating on web server attacks, we examine the attack manifestations available to intrusiondetection systems at different abstraction layers, includinga network-based IDS, an application-based IDS, andfinally a host-based IDS.Our findings include that attacks indeed have differentmanifestations depending on the audit source used. Someaudit sources may lack any manifestation for certain attacks, and, in other cases contain only events that are indirectly connected to the attack in question. This, in turn, affects the reliability of the attack detection if the intrusion detection system uses only a single audit source for collecting security-relevant events. Hence, we conclude that using a multisource detection model increases the probability of detecting a range of attacks directed toward the web server. We also note that this model should account for the detection quality of each attack / audit stream to be able to rank alerts.Keywords: intrusion detection, attack manifestations
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5.
  • Almgren, Magnus, 1972, et al. (author)
  • A Multi-Sensor Model to Improve Automated Attack Detection
  • 2008
  • In: 11th International Symposium, RAID 2008, Cambridge, MA, USA, September 15-17, 2008. Lecture Notes in Computer Science. - 9783540874027 ; 5230/2008, s. 291-310
  • Conference paper (peer-reviewed)abstract
    • Most intrusion detection systems available today are using a single audit source for detection, even though attacks have distinct manifestations in different parts of the system. In this paper we investigate how to use the alerts from several audit sources to improve the accuracy of the intrusion detection system (IDS). Concentrating on web server attacks, we design a theoretical model to automatically reason about alerts from different sensors, thereby also giving security operators a better understanding of possible attacks against their systems. Our model takes sensor status and capability into account, and therefore enables reasoning about the absence of expected alerts. We require an explicit model for each sensor in the system, which allows us to reason about the quality of information from each particular sensor and to resolve apparent contradictions in a set of alerts.Our model, which is built using Bayesian networks, needs some initial parameter values that can be provided by the IDS operator. We apply this model in two different scenarios for web server security. The scenarios show the importance of having a model that dynamically can adapt to local transitional traffic conditions, such as encrypted requests, when using conflicting evidence from sensors to reason about attacks.
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6.
  • Aulchenko, Yurii S, et al. (author)
  • Loci influencing lipid levels and coronary heart disease risk in 16 European population cohorts
  • 2009
  • In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 41:1, s. 47-55
  • Journal article (peer-reviewed)abstract
    • Recent genome-wide association (GWA) studies of lipids have been conducted in samples ascertained for other phenotypes, particularly diabetes. Here we report the first GWA analysis of loci affecting total cholesterol (TC), low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and triglycerides sampled randomly from 16 population-based cohorts and genotyped using mainly the Illumina HumanHap300-Duo platform. Our study included a total of 17,797-22,562 persons, aged 18-104 years and from geographic regions spanning from the Nordic countries to Southern Europe. We established 22 loci associated with serum lipid levels at a genome-wide significance level (P < 5 x 10(-8)), including 16 loci that were identified by previous GWA studies. The six newly identified loci in our cohort samples are ABCG5 (TC, P = 1.5 x 10(-11); LDL, P = 2.6 x 10(-10)), TMEM57 (TC, P = 5.4 x 10(-10)), CTCF-PRMT8 region (HDL, P = 8.3 x 10(-16)), DNAH11 (LDL, P = 6.1 x 10(-9)), FADS3-FADS2 (TC, P = 1.5 x 10(-10); LDL, P = 4.4 x 10(-13)) and MADD-FOLH1 region (HDL, P = 6 x 10(-11)). For three loci, effect sizes differed significantly by sex. Genetic risk scores based on lipid loci explain up to 4.8% of variation in lipids and were also associated with increased intima media thickness (P = 0.001) and coronary heart disease incidence (P = 0.04). The genetic risk score improves the screening of high-risk groups of dyslipidemia over classical risk factors.
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7.
  • Bergström, Göran, 1964, et al. (author)
  • Prevalence of Subclinical Coronary Artery Atherosclerosis in the General Population
  • 2021
  • In: Circulation. - Philadelphia : American Heart Association. - 0009-7322 .- 1524-4539. ; 144:12, s. 916-929
  • Journal article (peer-reviewed)abstract
    • Background: Early detection of coronary atherosclerosis using coronary computed tomography angiography (CCTA), in addition to coronary artery calcification (CAC) scoring, may help inform prevention strategies. We used CCTA to determine the prevalence, severity, and characteristics of coronary atherosclerosis and its association with CAC scores in a general population.Methods: We recruited 30 154 randomly invited individuals age 50 to 64 years to SCAPIS (the Swedish Cardiopulmonary Bioimage Study). The study includes individuals without known coronary heart disease (ie, no previous myocardial infarctions or cardiac procedures) and with high-quality results from CCTA and CAC imaging performed using dedicated dual-source CT scanners. Noncontrast images were scored for CAC. CCTA images were visually read and scored for coronary atherosclerosis per segment (defined as no atherosclerosis, 1% to 49% stenosis, or ≥50% stenosis). External validity of prevalence estimates was evaluated using inverse probability for participation weighting and Swedish register data.Results: In total, 25 182 individuals without known coronary heart disease were included (50.6% women). Any CCTA-detected atherosclerosis was found in 42.1%; any significant stenosis (≥50%) in 5.2%; left main, proximal left anterior descending artery, or 3-vessel disease in 1.9%; and any noncalcified plaques in 8.3% of this population. Onset of atherosclerosis was delayed on average by 10 years in women. Atherosclerosis was more prevalent in older individuals and predominantly found in the proximal left anterior descending artery. Prevalence of CCTA-detected atherosclerosis increased with increasing CAC scores. Among those with a CAC score >400, all had atherosclerosis and 45.7% had significant stenosis. In those with 0 CAC, 5.5% had atherosclerosis and 0.4% had significant stenosis. In participants with 0 CAC and intermediate 10-year risk of atherosclerotic cardiovascular disease according to the pooled cohort equation, 9.2% had CCTA-verified atherosclerosis. Prevalence estimates had excellent external validity and changed marginally when adjusted to the age-matched Swedish background population.Conclusions: Using CCTA in a large, random sample of the general population without established disease, we showed that silent coronary atherosclerosis is common in this population. High CAC scores convey a significant probability of substantial stenosis, and 0 CAC does not exclude atherosclerosis, particularly in those at higher baseline risk.
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8.
  • Bergström, Göran, et al. (author)
  • Prevalence of Subclinical Coronary Artery Atherosclerosis in the General Population
  • 2021
  • In: Circulation. - : Wolters Kluwer. - 0009-7322 .- 1524-4539. ; 144:12, s. 916-929
  • Journal article (peer-reviewed)abstract
    • Background: Early detection of coronary atherosclerosis using coronary computed tomography angiography (CCTA), in addition to coronary artery calcification (CAC) scoring, may help inform prevention strategies. We used CCTA to determine the prevalence, severity, and characteristics of coronary atherosclerosis and its association with CAC scores in a general population.Methods: We recruited 30 154 randomly invited individuals age 50 to 64 years to SCAPIS (the Swedish Cardiopulmonary Bioimage Study). The study includes individuals without known coronary heart disease (ie, no previous myocardial infarctions or cardiac procedures) and with high-quality results from CCTA and CAC imaging performed using dedicated dual-source CT scanners. Noncontrast images were scored for CAC. CCTA images were visually read and scored for coronary atherosclerosis per segment (defined as no atherosclerosis, 1% to 49% stenosis, or ≥50% stenosis). External validity of prevalence estimates was evaluated using inverse probability for participation weighting and Swedish register data.Results: In total, 25 182 individuals without known coronary heart disease were included (50.6% women). Any CCTA-detected atherosclerosis was found in 42.1%; any significant stenosis (≥50%) in 5.2%; left main, proximal left anterior descending artery, or 3-vessel disease in 1.9%; and any noncalcified plaques in 8.3% of this population. Onset of atherosclerosis was delayed on average by 10 years in women. Atherosclerosis was more prevalent in older individuals and predominantly found in the proximal left anterior descending artery. Prevalence of CCTA-detected atherosclerosis increased with increasing CAC scores. Among those with a CAC score >400, all had atherosclerosis and 45.7% had significant stenosis. In those with 0 CAC, 5.5% had atherosclerosis and 0.4% had significant stenosis. In participants with 0 CAC and intermediate 10-year risk of atherosclerotic cardiovascular disease according to the pooled cohort equation, 9.2% had CCTA-verified atherosclerosis. Prevalence estimates had excellent external validity and changed marginally when adjusted to the age-matched Swedish background population.Conclusions: Using CCTA in a large, random sample of the general population without established disease, we showed that silent coronary atherosclerosis is common in this population. High CAC scores convey a significant probability of substantial stenosis, and 0 CAC does not exclude atherosclerosis, particularly in those at higher baseline risk.
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9.
  • Bower, Hannah, et al. (author)
  • Are JAKis more effective among elderly patients with RA, smokers and those with higher cardiovascular risk? A comparative effectiveness study of b/tsDMARDs in Sweden.
  • 2023
  • In: RMD open. - : BMJ Publishing Group Ltd. - 2056-5933. ; 9:4
  • Journal article (peer-reviewed)abstract
    • To investigate whether the relative effectiveness of janus kinase inhibitors (JAKis) versus tumour necrosis factor inhibitors (TNFi) or other biological disease-modifying antirheumatic drugs in rheumatoid arthritis differ by the presence or absence of risk factors for cardiovascular (CV) disease, age, sex and smoking.Through Swedish registers, we identified 13493 individuals with 3166 JAKi, 5575 non-TNFi and 11 286 TNFi treatment initiations 2016-2022. All lines of therapy were included, with the majority in second line or higher. Treatment response was defined as the proportion reaching European Alliance of Associations for Rheumatology (EULAR) good response and Clinical Disease Activity Index (CDAI) remission, respectively, within 6 months. Crude percentage point differences in these proportions (JAKis, and non-TNFis, vs TNFis) overall and by risk factors were observed, and adjusted for confounders using linear regression models. Predicted probabilities of response and remission were estimated from adjusted Poisson models, and presented across CV risk and age.Overall, adjusted percentage point differences indicated higher response (+5.0%, 95% CI 2.2% to 7.9%) and remission (+5.8%, 95% CI 3.2% to 8.5%) with JAKis versus TNFis. The adjusted percentage point differences for response in those above 65, at elevated CV risk, and smokers were +5.9% (95% CI 2.7% to 9.0%), +8.3% (95% CI 5.3% to 11.4%) and +6.0% (95% CI 3.3% to 8.7%), respectively. The corresponding estimates for remission were +8.0% (95% CI 5.3% to 10.8%), +5.6% (95% CI 3.0% to 8.2%) and +7.6% (95% CI 5.5% to 9.7%).As used in clinical practice, response and remission at 6 months with JAKis are higher than with TNFi. Among patients with risk factors of concern, effectiveness is similar or numerically further increased. For individualised benefit-to-risk ratios to guide treatment choice, safety and effectiveness in specific patient segments should be considered.
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10.
  • Bower, H., et al. (author)
  • Effects of the COVID-19 pandemic on patients with inflammatory joint diseases in Sweden: from infection severity to impact on care provision
  • 2021
  • In: Rmd Open. - : BMJ. - 2056-5933. ; 7:3
  • Journal article (peer-reviewed)abstract
    • Objectives To compare risks for COVID-19-related outcomes in inflammatory joint diseases (IJDs) and across disease-modifying antirheumatic drugs (DMARDs) during the first two waves of the pandemic and to assess effects of the pandemic on rheumatology care provision. Methods Through nationwide multiregister linkages and cohort study design, we defined IJD and DMARD use annually in 2015-2020. We assessed absolute and relative risks of hospitalisation or death listing COVID-19. We also assessed the incidence of IJD and among individuals with IJD, rheumatologist visits, DMARD use and incidence of selected comorbidities. Results Based on 115 317 patients with IJD in 2020, crude risks of hospitalisation and death listing COVID-19 (0.94% and 0.33% across both waves, respectively) were similar during both waves (adjusted HR versus the general population 1.33, 95% CI 1.23 to 1.43, for hospitalisation listing COVID-19; 1.23, 95% CI 1.08 to 1.40 for death listing COVID-19). Overall, biological disease-modifying antirheumatic drugs (bDMARDs)/targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs) did not increase risks of COVID-19 related hospitalisation (with the exception of a potential signal for JAK inhibitors) or death. During the pandemic, decreases were observed for IJD incidence (-7%), visits to rheumatology units (-16%), DMARD dispensations (+6.5% for bDMARD/tsDMARDs and -8.5% for conventional synthetic DMARDs compared with previous years) and for new comorbid conditions, but several of these changes were part of underlying secular trends. Conclusions Patients with IJD are at increased risk of serious COVID-19 outcomes, which may partially be explained by medical conditions other than IJD per se. The SARS-CoV-2 pandemic has exerted measurable effects on aspects of rheumatology care provision demonstrated, the future impact of which will need to be assessed.
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11.
  • Bower, Hannah, et al. (author)
  • Impact of the COVID-19 pandemic on morbidity and mortality in patients with inflammatory joint diseases and in the general population : a nationwide Swedish cohort study
  • 2021
  • In: Annals of the Rheumatic Diseases. - : BMJ Publishing Group Ltd. - 0003-4967 .- 1468-2060. ; 80:8, s. 1086-1093
  • Journal article (peer-reviewed)abstract
    • Objectives: To estimate absolute and relative risks for all-cause mortality and for severe COVID-19 in inflammatory joint diseases (IJDs) and with antirheumatic therapies.Methods: Through Swedish nationwide multiregister linkages, we selected all adult patients with rheumatoid arthritis (RA, n=53 455 in March 2020), other IJDs (here: spondyloarthropathies, psoriatic arthritis and juvenile idiopathic arthritis, n=57 112), their antirheumatic drug use, and individually matched population referents. We compared annual all-cause mortality March-September 2015 through 2020 within and across cohorts, and assessed absolute and relative risks for hospitalisation, admission to intensive care and death due to COVID-19 March-September 2020, using Cox regression.Results: During March-September 2020, the absolute all-cause mortality in RA and in other IJDs was higher than 2015-2019, but relative risks versus the general population (around 2 and 1.5) remained similar during 2020 compared with 2015-2019. Among patients with IJD, the risks of hospitalisation (0.5% vs 0.3% in their population referents), admission to intensive care (0.04% vs 0.03%) and death (0.10% vs 0.07%) due to COVID-19 were low. Antirheumatic drugs were not associated with increased risk of serious COVID-19 outcomes, although for certain drugs, precision was limited.Conclusions: Risks of severe COVID-19-related outcomes were increased among patients with IJDs, but risk increases were also seen for non-COVID-19 morbidity. Overall absolute and excess risks are low and the level of risk increases are largely proportionate to those in the general population, and explained by comorbidities. With possible exceptions, antirheumatic drugs do not have a major impact on these risks.
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12.
  • Di Giuseppe, D., et al. (author)
  • Comparison of treatment retention of originator vs biosimilar products in clinical rheumatology practice in Sweden
  • 2021
  • In: Rheumatology. - : Oxford University Press (OUP). - 1462-0324 .- 1462-0332. ; 61:9, s. 3596-3605
  • Journal article (peer-reviewed)abstract
    • Objectives To compare treatment retention between biosimilars and their originator products among first starters (etanercept, infliximab, adalimumab and rituximab), as well as after non-medical switch. Methods Patients with rheumatic diseases starting, for the first time, an originator or biosimilar etanercept, infliximab, adalimumab or rituximab were identified in the national Swedish Rheumatology Quality Register. Moreover, patients switching from an originator to its biosimilar were identified and individually matched to patients continuing on the originator. One-year treatment retention was calculated and hazard ratios (HR) for discontinuation with 95% CIs were estimated, adjusting for comorbidities and socio-economic factors. Results In total, 21 443 first treatment courses were identified. The proportion of patients still on the drug at 1 year and the HR for discontinuation revealed no differences across adalimumab (Humira, Imraldi, Amgevita and Hyrimoz) nor across rituximab products (Mabthera, Ritemvia/Truxima and Rixathon). The proportions on the drug at 1 year were similar for Benepali (77%) and Enbrel (75%) and the adjusted HR for Benepali compared with Enbrel was 0.91 (95% CI 0.83, 0.99). For infliximab, the proportion still on the drug at 1 year was 67% for Remicade and 66% for Remsima/Inflectra and the HR compared with Remicade was 1.16 (95% CI 1.02, 1.33). Among 2925 patients switching from an originator drug to one of its biosimilars, we noted no statistically significant or clinically relevant differences in drug survival compared with those who remained on originator therapy. Conclusion This large observational study supports the equivalence of biologic DMARD biosimilar products and originators when used in routine rheumatology care.
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13.
  • Di Giuseppe, D., et al. (author)
  • Uptake of rheumatology biosimilars in the absence of forced switching
  • 2018
  • In: Expert Opinion on Biological Therapy. - : Informa UK Limited. - 1471-2598 .- 1744-7682. ; 18:5, s. 499-504
  • Journal article (peer-reviewed)abstract
    • Background: To describe the uptake and system-level effects of the introduction of biosimilars in a setting without forced switching.Research design and methods: We used data from the Swedish Rheumatology Quality register from start of marketing of infliximab (Remsima (R) and Inflectra (R)) and etanercept (Benepali (R)) biosimilars until 31 December 2016. We compared users of each originator-product and its biosimilar(s) by line of treatment: bDMARD-naive patients, non-medical switchers (vs. matched patients remaining on originator), and patients switching from a previous bDMARD of another type.Results: From the start of marketing 1343 patients started an infliximab biosimilar (22 months) and 2691 started etanercept (9months). Overall, the introduction of these biosimilars resulted in an increase of the total number of ongoing infliximab and etanercept treatments (originator + biosimilar) . At the end of the study period, biosimilars accounted for 31% of all infliximab treatments and 31% of all etanercept-treated patients. For each line of therapy, we noted only small differences in patient characteristics between those starting the originator product vs. its biosimilar(s).Conclusions: Introduction of biosimilars have effects beyond replacement of the originator product, in terms of an increased rate of bDMARD initiation. Selection to non-medical switching displayed no particular disease- or patient-characteristics.
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14.
  • Enoksson, Emmi (author)
  • Studies on image control for better reproduction in offset
  • 2006
  • Licentiate thesis (other academic/artistic)abstract
    • This research work has focused on studies of image control for better reproduction in offset and has been applied practically. This research work has resulted in a survey of color management knowledge, a communication list concerning ICC profiles, an educational kit, a proposal for a new terminology and a patent concerning image adaptation. The work is divided into following three areas: 1) image classification A better understanding of image processing can avoid misunderstandings in the print and leading to more satisfied customers. To achieve optimal print quality for different images, it is important to adapt the prepress settings to the image category. Images can be divided into different categories depending on their image content, key information and tone distribution. Trials have been carried out in which the IT.8 test chart has been adapted to different image categories. The results of the image adaptation suggest that an adjustment only to low-key images (dark images) is sufficient, as even normal-key images then show a better similarity to the original image. The low-key image showed more details in dark areas. 2) color separation Two studies has been carried out. The purpose has been to investigate the knowledge level in color separation, the use of ICC-profiles and the understanding of color management in various printing houses in Sweden. This was done to identify and suggest new applications and suggested actions. These studies indicate that there is a serious problem in the graphic arts industry. The problem is that there is both an insufficient knowledge of color management and a lack of communication. There is a lack of competence and a lack of literature and instructions which can help printers to better understand the technology, and communication suffers through a lack of a common language. 3) suggested actions and the development of tools Terminology simplification is crucial for the users. A new term for separation “Compensation by Black”, CB, has been suggested. A single term should make it easier for the users to understand and use the different settings which impact the image reproduction. A new tool/kit for the evaluation of ICC-profiles has been created. The goal of this educational kit is to facilitate and exemplify the practical understanding of profiles and their use for the users.
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15.
  • Enoksson, Emmi, 1960- (author)
  • Toward better image reproduction in offset
  • 2010
  • Doctoral thesis (other academic/artistic)abstract
    • This thesis has focused on color reproduction processes in the graphics field and is based on theoretical research and practical studies. The purpose of this thesis was to investigate how new tools and tools adapted to a specific production set-up can be used to raise awareness regarding the quality and workflow of images and image processing for sheet-fed offset within the graphic industry. The work is divided in to the following three study areas with several sub-studies: 1) The first research goal of the thesis is to identify knowledge levels regarding color separation of images and demand specifications within printing houses. 2) The second research goal is to investigate whether novel tools and new terminology can help to increase the knowledge level regarding color management 3) The third goal is to investigate whether process specific adaptation of key color control tools can improve quality levels Three surveys about color reproduction (focusing on level of knowledge concerning color separation, the use of ICC-profiles and demand specifications for controlled color reproduction) at printing companies in Sweden were made between 2000 and 2004. The surveys indicated a serious problem in the graphic arts industry, involving both an insufficient understanding of color management and a lack of communication. An important part of the work was to assist in make color management understandable for users and thereby optimize printing. For this purpose, digital test forms have been developed. The developed tools, together with descriptive material, will facilitate the understanding of color management issues. Definitions within the field of color separations have been examined, and changes have been suggested. A new term for separation “Compensation by Black”, CB, has been suggested, instead of e.g. GCR and UCR. Is it possible to adapt the different parts of the process chain in order to achieve an improved production? Yes! This work has developed the method for adaptation of the scanne rtest chart, the printing test chart for image categorization and the control strip forsheet-fed offset using gray balance. This thesis suggests that it is possible to produce a custom-made IT8 target test chart for scanners and achieve a result at least similar to or even better than the standard test charts on the market. This work has also shown that itis possible to adapt the test chart for printing to image category. The result showed that low-key image separated by the image-adapted test chart showed more detail in the dark areas than a low-key image separated by the standard test chart, in the prints on a coated paper. The result from the adaptation of a control strip for sheet-fed offset showed that gray balance can be used as a control parameter for quality control in sheet-fed offset.
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16.
  • Enroth, Maria, 1960- (author)
  • Developing tools for sustainability management in the graphic arts industry
  • 2006
  • Doctoral thesis (other academic/artistic)abstract
    • The main aim of this thesis is to develop and test industry-specific, applied work procedures and tools for environmental and emerging sustainability work in the graphic arts industry. This includes methods to quantify, follow-up, evaluate, manage, improve and communicate the environmental performance of activities in the graphic arts supply chain and printed products.In order to achieve the aims of the thesis, a selection of work areas were chosen as the basis for developing the industry-specific work procedures and tools. The selected work areas are the following: environmental management (being a part of sustainability management), environmental and sustainability strategies, environmental indicators and design for environment (DfE).The research presented in this thesis was based on survey research methods, case studies and multi-company studies. Within the framework of these methods, quantitative and qualitative techniques for data gathering were used. The companies included in the studies were selected according to their willingness, interest and motivation to participate and develop their environmental or sustainability work.The most significant results of the research presented in this thesis regarding the selected work areas are the following:• An evaluation of early certified environmental management systems (EMSs) in Sweden identified four areas as priorities in making the EMSs more efficient. Two of them, viz. improvement in the follow-up of environmental work, and the linking of EMSs to product design, were developed for the graphic arts industry. The remaining two areas were clarifying the identification process and assessment of environmental aspects, and streamlining and co-ordinating different management systems.• An established and successfully tested working method for formulating and realising corporate sustainability strategies in the graphic arts industry.• Industry-specific environmental indicator models for the graphic arts industry with defined methods for standardised inventorying and calculations. These models have been tested, used and approved of by the industry itself.• Collected and compiled data for the developed environmental indicator models. Data have been collected from quite a large number of companies (10-20 companies for each of the printing techniques covered, i.e. coldset offset, heatset offset and gravure) over a period of several years.• The use of the industry-specific environmental indicator models was developed and illustrated.• A described and recommended work procedure for DfE in graphic arts companies including industry-specific tools for applying DfE to printed products, in the form of a manual and a checklist. The checklist was designed so that it can serve as a simple tool for the environmental assessment of printed products. The tools were tested by graphic arts companies.
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17.
  • Forsström, Stefan, 1984-, et al. (author)
  • Surveying and identifying the communication platforms of the internet of things
  • 2018
  • In: 2018 Global Internet of Things Summit, GIoTS 2018. - : IEEE. - 9781538664513
  • Conference paper (peer-reviewed)abstract
    • Research and industry invest time and resources in producing Internet of Things-based services, and the concept of Internet of Things platforms is climbing in the hype cycle for emerging technologies. Consequently, there is a vast number of enabling technologies, making it difficult to find the most suitable platform. The aim and goal of this article is to list and identify the currently available communication platforms for the Internet of Things. In this workwe surveyed the area and found over 128 different platforms for communication of data between things and services, out of which 42 fulfilled our listed basic requirements for being an IoT communication platform.
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18.
  • Fransson, Martin, 1978-, et al. (author)
  • A preliminary study of modeling and simulation in individualized drug dosage – azathioprine on inflammatory bowel disease
  • 2007
  • In: SIMS 2006: Proceedings of the 47th Conference on Simulation and Modelling, Helsinki, Finland. - Helsinki : Kopio Niini Oy. - 9525183300 ; , s. 216-220
  • Conference paper (peer-reviewed)abstract
    • Individualized drug dosage based on population pharmacokinetic/dynamic models is an important future technology used to reduce or eliminate side effects of certain drugs, e.g. cancer drugs. In this paper we report preliminary results from work-in-progress: a simplified linear model of the metabolism of a cancer treatment drug was estimated from experimental data. The model was then validated against the same data as a test of the adequacy of the model structure. From this investigation it became apparent that the model structure could not be used due to its inability to recreate the dynamic properties of the system.
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19.
  • Fridén, Michael (author)
  • Role of Fatty Acid Composition in Non-Alcoholic Fatty Liver Disease: a Dietary Perspective : Results from Interventional and Observational Studies
  • 2024
  • Doctoral thesis (other academic/artistic)abstract
    • The overall aim of this doctoral thesis was to investigate the role of circulating, liver and dietary fatty acids in non-alcoholic fatty liver disease (NAFLD). For circulating and liver fatty acids, special emphasis was given to fatty acids reflecting diet.In paper I, circulating cholesteryl ester (CE) linoleic acid (18:2n-6), which is considered a good biomarker of dietary intake of 18:2n-6, was cross-sectionally inversely associated with liver fat in n=308 50-year old men and women. Several fatty acids reflecting both exogenous intake and endogenous metabolism were associated with liver fat, basal fat oxidation and resting energy expenditure (REE). No association between fatty acids and liver fat, except for docosahexaenoic acid (22:6n-3) and liver fat, were attenuated after adjusting for REE. In paper II, phospholipid (PL) 22:6n-3 in liver tissue, a potential biomarker of dietary intake of 22:6n-3, was cross-sectionally inversely associated with liver fibrosis in n=60 men and women with biopsy-verified NAFLD. This finding was not replicated in plasma. Several other fatty acids reflecting both exogenous intake and endogenous metabolism were associated with fibrosis. Pooled saturated fatty acids (SFA) were generally positively associated whereas monounsaturated (MUFA) and polyunsaturated fatty acids (PUFA) were inversely associated with fibrosis. In paper III, no clear (i.e. imprecise) associations were observed for any of the nutrient or food substitutions with incidence NAFLD cirrhosis or hepatocellular carcinoma (HCC), over a median follow-up of 24 years in n>77 000 middle-aged to elderly men and women. In paper IV, a 12-month randomized controlled trial (RCT) was conducted to investigate the effects of a low-carbohydrate high PUFA (LCPUFA) diet and a healthy Nordic diet (HND) on liver fat in men and women with type 2 diabetes (T2D) or prediabetes. The comparator diet (usual care (UC)) aligned with the Nordic Nutrition Recommendations. Liver fat decreased more in the LCPUFA diet and the HND versus UC. No difference in liver fat was observed between LCPUFA and HND. The LCPUFA diet and the HND improved several other cardiometabolic markers compared to UC, with more favorable improvements in the HND group.In conclusion, findings from this thesis suggest that higher intakes of dietary unsaturated fatty acids (in particular PUFA) and lower intakes of SFA may be of importance for the prevention and treatment of NAFLD (at least for liver fat and fibrosis). Findings from this thesis also suggest that fatty acids reflecting both diet and endogenous metabolism may play a role in NAFLD. 
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20.
  • Frisell, T., et al. (author)
  • Safety of biological and targeted synthetic disease-modifying antirheumatic drugs for rheumatoid arthritis as used in clinical practice: results from the ARTIS programme
  • 2023
  • In: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 82:5
  • Journal article (peer-reviewed)abstract
    • ObjectiveLongitudinal clinical registry-infrastructures such as Anti-Rheumatic Therapies in Sweden (ARTIS) allow simultaneous comparison of the safety of individual immunomodulatory drugs used in clinical practice, with consistent definitions of treatment cohorts, follow-up and outcomes. Our objective was to assess and compare incidence rates of key safety outcomes for individual targeted synthetic or biological disease-modifying antirheumatic drugs (b/ts DMARDs) in rheumatoid arthritis (RA), updating previous reports and including newer treatments including Janus Kinase inhibitors (JAKi). MethodsNationwide register-based cohort study including all patients with RA in Sweden registered as starting any b/tsDMARD 1 January 2010 through 31 December 2020, followed until 30 June 2021 (N=20 117). The incidence rates of selected outcomes, identified through national healthcare registers, were compared between individual b/tsDMARDs, adjusted for confounding by demographics, RA disease characteristics and comorbidity. ResultsThere were marked differences in treatment discontinuations due to adverse events (rates per 1000 person-years ranged from 18 on rituximab to 57 on tofacitinib), but few significant differences were observed for the serious adverse events under study. Neither cardiovascular events nor general serious infections were more frequent on baricitinib or tofacitinib versus bDMARDs, but JAKi were associated with higher rates of hospital-treated herpes zoster (HR vs etanercept, 3.82 (95% CI 2.05 to 7.09) and 4.00 (1.59 to 10.06)). Low number of events limited some comparisons, in particular for sarilumab and tofacitinib. ConclusionData from ARTIS supports that the b/tsDMARDs currently used to treat RA have acceptable and largely similar safety profiles, but differences exist in particular concerning tolerability and specific infection risks.
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21.
  • Glendor, Ulf, et al. (author)
  • Direct and indirect costs of dental trauma in Sweden : a 2-year prospective study of children and adolescents
  • 2001
  • In: Community Dentistry and Oral Epidemiology. - : Wiley. - 0301-5661. ; 29:2, s. 150-160
  • Journal article (peer-reviewed)abstract
    • OBJECTIVES: To study total costs, including direct costs (health care service, loss of personal property, medicine and transport) and indirect costs (loss of production or leisure) of dental trauma to children and adolescents with special reference to predictors. METHODS: The study was based on a random sample of 192 children and adolescents with a dental trauma reported to an insurance company and prospectively followed up by telephone interviews over a period of 2 years. RESULTS: On average, health care service costs represented 2,955 SEK (SD=3,818) and total costs 4,569 SEK (SD=3,053) for dental trauma to permanent teeth, and 837 SEK (SD=898) and 1,746 SEK (SD=1,183) for trauma to primary teeth. The most extensive type of indirect cost was loss of production or leisure, which averaged 1,286 SEK (SD=1,830) for injuries to permanent teeth and 699 SEK (SD=1,239) for injuries to primary teeth. Multiple regression analysis of demographic and dental injury variables showed that complicated trauma was of special importance to costs for permanent and primary teeth injuries. The average relative increase in total costs to patients and companions for complicated injury to permanent teeth was 140% (95% confidence interval [CI], 66-248%) for patients and 132% (95% CI, 54-249%) for companions. Lack of access to a dental clinic near the place of residence could increase the average total costs of injuries to permanent teeth by 91% for companions (95% CI, 20-204%) and for primary teeth by 134% (95% CI, 38-296%). CONCLUSIONS: Dental traumas result in both direct and indirect costs, with a predominance of direct costs. The direct costs primarily depend on degree of severity, while indirect costs are mostly due to compromised access to health care service. Traumas to permanent teeth are especially costly and, due to additional maintenance, the care may continue for several years. This study has drawn attention to the significant implications of dental trauma to patient and companion, a new area where further studies are warranted.
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22.
  • Gustafsson, Anna, et al. (author)
  • Kartering av limniska naturvärden - Lovön, Kärsön och Fågelön m.fl. öar 2011
  • 2012
  • Reports (other academic/artistic)abstract
    • Föreliggande rapport redovisar en naturinventering av sjöstränderna i det planerade naturreservatet Lovön-Kärsön i Mälaren. Inventeringen utfördes i syfte att beskriva och bedöma strändernas limniska naturvärden och omfattade biotopkartering samt riktade undersökningar av vattenväxter, bottendjur och stormusslor. Karteringen utfördes i juli-oktober 2011 av Naturvatten AB på uppdrag av Länsstyrelsen i Stockholms län. Resultatet redovisas i text och kartor i denna rapport, samt i en biotopkarteringsdatabas (Access) framtagen av länsstyrelsen. Inventeringen omfattade sammantaget 188 biotoper som täcker in en strandsträcka av cirka 45 kilometer. Ingen av biotoperna bedömdes till den högsta klassen naturvärde av nationell betydelse. Tjugo biotoper motsvarande 13 procent av stränderna, bedömdes till naturvärde av regional betydelse. Av dessa biotoper fördelade sig åtta till Lovön och tolv till Kärsön. Bedömning till regionalt värde motiverades av förekomst av rödlistade arter, regionalt sett ovanliga arter och/eller Natura 2000- naturtyper av hög kvalitet. Hela 65 biotoper, motsvarande 40 procent av stränderna, bedömdes till naturvärde av kommunal betydelse. Bedömningarna grundar sig bland annat på artrikedom, strukturell mångformighet samt ekologisk funktion i form av framförallt lekområden för fisk eller bottnar med särskilt goda förutsättningar för kräftor. Det inventerade området var som helhet att betrakta som mycket artrikt både vad gäller vattenväxter och bottendjur. Artrikedomen varierade dock kraftigt mellan biotoperna. Tre rödlistade arter noterades vid fältarbetet, nämligen vattenväxterna bandnate och uddnate samt stormusslan äkta målarmussla. Samtliga redovisas som nära hotade (NT) i 2010 års rödlista. Vidare förekommer i området ett antal arter som kan anses vara ovanliga i regionen och som stärker dess naturvärden. En statusklassning enligt Naturvårdsverkets bedömningsgrunder visade på måttlig ekologisk status för vattenväxter, och god eller hög status för bottenfauna. Diskrepansen i klassningen av de båda organismgrupperna förklaras förmodligen till största delen av brister i bedömningsgrunderna. Generellt tenderar bedömningsgrunderna för bottenfauna i strandzonen att ge en överskattat god bild av det verkliga tillståndet, medan bedömningssystemet för vattenväxter inte förmår skilja naturligt näringsrika vatten från de som är övergödda.
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23.
  • Gustafsson, Anna, et al. (author)
  • Vattenväxter i Sillen - vegetationsinventering 2019
  • 2019
  • Reports (other academic/artistic)abstract
    • Denna rapport presenterar resultat från inventering av vattenvegetationi sjön Sillen i Stockholms län 2019. Inventeringensyftade till uppföljande övervakning av sjöns växtsamhälle samttill uppdaterad statusklassificering av ekologisk status avseendemakrofyter och utfördes av Naturvatten AB på uppdrag avLänsstyrelsen i Stockholms län.Vid inventeringen noterades 33 arter av vattenvegetation, övervattensväxterundantaget. Smal vattenpest var vanligast förekommande i Sillen. Arten sominte noterades i sjön överhuvudtaget vid föregående inventering, år 2010, ärinvasiv och främmande för den svenska floran och har numera stor spridning iregionen. Släktingen vattenpest noterades båda åren sparsamt i Sillen.Vid inventeringen 2019 gjordes fynd av fem rödlistade arter, nämligenkransalgen barklöst sträfse och bandnate i hotkategorin sårbar (VU) samtpilblad, ävjebrodd och uddnate som är rödlistade i kategorin nära hotad (NT).Av dessa är fyndet av den rödlistade kransalgen att betrakta som det allra mestintressanta och något av en sensation med tanke att arten sedan tidigare endastär känd från ett fåtal lokaler i landet (Norrbottens kustområde, Östergötland,Skåne).Djupast förekommande arter var smal vattenpest och spärrkrokmossa sompåträffades på 3,1 meter. I jämförelse med tidigare inventering förefallervegetationens djuputbredning ha ökat med cirka en halvmeter. Bedömningenmåste ses som osäker. En klassificering baserad på makrofyter indikerar måttligekologisk status. Det innebär en att bedömningen är oförändrad i jämförelsemed föregående klassning, baserad på inventering år 2010*.*
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24.
  • Gustafsson, Ulf, 1976-, et al. (author)
  • Apical circumferential motion of the right and the left ventricles in healthy subjects described with speckle tracking
  • 2008
  • In: Journal of the American Society of Echocardiography. - : Elsevier BV. - 0894-7317 .- 1097-6795. ; 21:12, s. 1326-1330
  • Journal article (peer-reviewed)abstract
    • Background The aim of this study was to determine whether right ventricular (RV) apical rotation could be of importance in RV function and compare this with left ventricular (LV) apical rotation. Methods Short-axis images at the apical level of both ventricles were simultaneously recorded in 14 healthy subjects (mean age, 62 ± 11 years). Results There was a significant difference in mean rotation between the two ventricles in the time interval between 50% of ejection and aortic valve closure (P < .05). At aortic valve closure, LV rotation was 10.9 ± 4.8° counterclockwise, and RV rotation was 1.1 ± 5.8° clockwise. The anterior and inferior parts of the right ventricle rotated in opposite directions toward the septum. The septal segments of both ventricles rotated inferiorly, thus likely reducing interventricular stress. Conclusion This study showed clear differences in apical rotation between the two ventricles. Whereas the left ventricle displayed uniform rotation, the right ventricle showed heterogeneous rotation, resulting overall in almost no rotation but in a “tightening belt” motion.
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25.
  • Gustafsson, Ulf, 1976-, et al. (author)
  • Assessment of regional rotation patterns improves the understanding of the systolic and diastolic left ventricular function : an echocardiographic speckle-tracking study in healthy individuals
  • 2009
  • In: European Journal of Echocardiography. - : Oxford University Press (OUP). - 1525-2167 .- 1532-2114. ; :10, s. 56-61
  • Journal article (peer-reviewed)abstract
    • AIM To elucidate the complexity of left ventricular motion throughout the cardiac cycle, we studied regional rotation in detail. METHODS AND RESULTS: Regional rotation in six subdivisions of the circumference at three levels was studied by using speckle-tracking echocardiography in 40 healthy subjects. At the basal level the inferoseptal segments rotated significantly more clockwise during systole than the opposing anterolateral segments. At the papillary level the inferoseptal segments differed significantly from the anterolateral segments, where the inferoseptal segments rotated clockwise and the anterolateral segments rotated counter-clockwise. The apical level showed significant difference in regional rotation only at aortic valve opening. In early systole, untwist before the main systolic twist was seen at the basal and apical levels; however, the duration of the basal untwist was much longer than that of the apical. The diastolic phases of rotation at the basal and apical levels matched the different filling phases. CONCLUSION: Large regional differences in rotation are present at the basal and papillary levels in healthy subjects. The diastolic untwist matches the phases of both the E-wave and A-wave and seems to be related with intraventricular pressure differences, indicating that untwist plays an important role in the filling of the ventricle.
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26.
  • Gustafsson, Ulf, 1976-, et al. (author)
  • The effect of acute myocardial ischemia on the rotation axis of the left ventricle
  • Other publication (other academic/artistic)abstract
    • Introduction: We have developed a method to assess the axis around which the left ventricle (LV) rotates. The aim was to assess the effect of acute regional ischemia on the otation axis. Method: Mid‐LAD occlusion was induced in six anesthetised pigs and echocardiographic images were recorded at baseline and after LAD occlusion. The rotation axis was calculated at three different levels of the LV throughout the cardiac cycle. Results: The direction of the rotation axis was significantly changed (p<0.01) after LAD occlusion, being directed towards the ischemic area. AV‐plane displacement was significantly reduced (p<0.05) during ischemia. No significant difference in twist or otation amplitudes was found. Conclusion: This new method of assessing rotational function seems as sensitive as AV‐plane displacement and superior to traditional rotation and twist parameters in detecting dysfunction in acute ischemic myocardium. The rotation axis method has the advantage of potentially identifying areas with dysfunction.
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27.
  • Gustafsson, Ulf, 1976-, et al. (author)
  • The rotation axis of the left ventricle : a new concept derived from ultrasound data in healthy individuals
  • Other publication (other academic/artistic)abstract
    • Introduction: The axis around which the left ventricle (LV) rotates has never previously been described. The aim was to develop a method to calculate the spatial motion of the rotation axis throughout the cardiac cycle. Method: By constructing a model of the LV, based on dimensions and rotation values at the basal, mid ventricular and apical levels, a rotation axis could be calculated at each level in 39 healthy subjects. The transition plane, defined as the level without rotation, where basal and apical rotation meet was also calculated. Results: The rotation axis was not congruent to the longitudinal axis of the LV at any time point. A significant and specific mean direction for each of the rotation axes for the majority of the tested time points displayed a physiological pattern. Conclusion: This new method introduces a new concept in cardiac function and provides further insight into the complexity of LV mechanics.
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28.
  • Gustafsson, Ulf, 1976- (author)
  • Ventricular rotation and the rotation axis : a new concept in cardiac function
  • 2010
  • Doctoral thesis (other academic/artistic)abstract
    • Background: The twisting motion of the left ventricle (LV), with clockwise rotation at the base and counter clockwise rotation at the apex during systole, is a vital part of LV function. Even though LV rotation has been studied for decades, the rotation pattern has not been described in detail. By the introduction of speckle tracking echocardiography measuring rotation has become easy of access. However, the axis around which the LV rotates has never before been assessed. The aims of this thesis were to describe the rotation pattern of the LV in detail (study I), to assess RV apical rotation (study II), develop a method to assess the rotation axis (study III) and finally to study the effect of regional ischemia to the rotation pattern of the LV (study IV). Methods: Healthy humans were examined in study I-III and the final study populations were 40 (60±14 years), 14 (62±11 years) and 39 (57±16 years) subjects, respectively. In study IV six young pigs (32-40kg) were studied. Standard echocardiographic examinations were performed. In study IV the images were recorded before and 4 minutes after occlusion of left anterior descending coronary artery (LAD). Rotation was measured in short axis images by using a speckle tracking software. By development of custom software, the rotation axis of the LV was calculated at different levels in every image frame throughout the cardiac cycle. Results: Study I showed significant difference in rotation between basal and apical rotations, as well as significant differences between segments at basal and mid ventricular levels. The rotation pattern of the LV was associated with different phases of the cardiac cycle. Study II found significant difference in rotation between the LV and the RV. RV rotation was heterogeneous and bi-directional, creating a ´tightening belt action´ to reduce it circumference. Study III indicated that the new method could assess the rotation axis of the LV. The motion of the rotation axes in healthy humans displayed a physiological and consistent pattern. Study IV found a significant difference in the rotation pattern, between baseline and after LAD occlusion, by measuring the rotation axes, but not by conventional measurements of rotation. AV-plane displacement and wall motion score (WMS) were also significantly changed after inducing regional ischemia. Conclusion: There are normally large regional differences in LV rotation, which can be associated anatomy, activation pattern and cardiac phases, indicating its importance to LV function. In difference to the LV, the RV did not show any functional rotation. However, its heterogeneous circumferential motion could still be of importance to RV function and may in part be the result of ventricular interaction. The rotation axis of the LV can now be assessed by development of a new method, which gives a unique view of the rotation pattern. The quality measurements and results in healthy humans indicate that it has a potential clinical implication in identifying pathological rotation. This was supported by the experimental study showing that the rotation axis was more sensitive than traditional measurements of rotation and as sensitive as AV-plane displacement and WMS in detecting regional myocardial dysfunction.
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29.
  • Hildebrand Karlén, Malin, 1984, et al. (author)
  • Prevalence and heritability of alcohol use disorders in 18-year old Swedish twins
  • 2023
  • In: Nordic Studies on Alcohol and Drugs. - 1455-0725. ; 40:4
  • Journal article (peer-reviewed)abstract
    • Background: Heritability of alcohol use disorders (AUDs) varies widely, with reported estimates of 30-78% in twin studies. This variation might be due to methodological differences (e.g., using different thresholds for AUDs, age differences between samples). Aim: To investigate the heritability of AUDs in a nation-wide sample of male and female twins in late adolescence (18 years). Participants: The study is based on data from 8,330 18-year-old Swedish monozygotic (MZ) and dizygotic (DZ) twins from the Child and Adolescent Twin Study (Sweden). Method: Univariate sex-limitation twin analyses were performed using (a) total AUDIT score, (b) different AUDIT cut-offs (AUDIT-10: potentially harmful alcohol use and most likely alcohol dependent ; AUDIT-C: potential hazardous alcohol consumption/active alcohol use disorders), and (c) a risk-group classification for alcohol dependence based on AUDIT total score. Results: Prevalence of potential hazardous alcohol consumption/active alcohol use was 57.1%, and for potentially harmful alcohol use prevalence was 26.5%. Prevalence was higher among females (59.0% and 31.1% respectively) than males (54.4% and 20.0% respectively). Overall, the results of the univariate model fitting indicated that there were qualitative sex differences in the genetic and environmental influences on AUDs, with generally moderate heritability estimates ranging between 0.37 and 0.50. Discussion: At odds with previous research, a harmful/hazardous drinking pattern was more common in this age group among females than a low-risk drinking pattern (where males were overrepresented). Heritability estimates were moderate throughout all measures and cut-offs, with equally high contributions from shared and non-shared environment. Sex-limitation models revealed qualitative sex differences for AUDs, suggesting that different genetic and/or environmental factors influence variation in AUDs in males and females.
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30.
  • Hindorf, Ulf, et al. (author)
  • Adverse events leading to modification of therapy in a large cohort of patients with inflammatory bowel disease
  • 2006
  • In: Alimentary Pharmacology and Therapeutics. - : Wiley. - 0269-2813 .- 1365-2036. ; 24:2, s. 331-342
  • Journal article (peer-reviewed)abstract
    • Background: Adverse events leading to discontinuation or dose reduction of thiopurine therapy occur in 9-28% of patients with inflammatory bowel disease. Aims: To evaluate the influence of thiopurine methyltransferase status and thiopurine metabolites in a large patient population for the risk of developing adverse event. Methods: Three hundred and sixty-four patients with inflammatory bowel disease and present or previous thiopurine therapy were identified from a local database. Results: The adverse event observed in 124 patients (34%) were more common in adults than children (40% vs. 15%, P < 0.001) and in low to intermediate (≤9.0 U/mL red blood cell) than normal thiopurine methyltransferase activity (P = 0.02). Myelotoxicity developed later than other types of adverse event. An increased frequency of adverse event was observed in patients with tioguanine (thioguanine) nucleotide above 400 or methylated thioinosine monophosphate above 11 450 pmol/ 8 × 108 red blood cell. A shift to mercaptopurine was successful in 48% of azathioprine-intolerant patients and in all cases of azathioprine-induced myalgia or arthralgia. Conclusions: A pre-treatment determination of thiopurine methyltransferase status might be appropriate as patients with low to intermediate thiopurine methyltransferase activity are more prone to develop an adverse event, determination of metabolite levels can be useful in the case of an adverse event. Mercaptopurine therapy should be considered in azathioprine-intolerant patients. © 2006 The Authors.
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31.
  • Hindorf, Ulf, et al. (author)
  • Genotyping should be considered the primary choice for pre-treatment evaluation of thiopurine methyltransferase function
  • 2012
  • In: Journal of Crohn's and Colitis. - : Elsevier. - 1873-9946. ; 6:6, s. 655-659
  • Journal article (peer-reviewed)abstract
    • Background and aimsA pre-treatment determination of the thiopurine S-methyltransferase (TPMT) genotype or phenotype can identify patients at risk of developing severe adverse reactions from thiopurine treatment. The risk of misclassifying a patient might be dependent on the method used. The aim of this study was to investigate the concordance between TPMT genotyping and phenotyping.MethodsThe data consist of 7195 unselected and consecutive TPMT genotype and phenotype determinations sent to the division of Clinical Pharmacology, Linköping, Sweden. TPMT activity was measured in red blood cells (RBC) and the genotype determined by pyrosequencing for the three most common TPMT variants (TPMT *2, *3A, *3C).ResultsTPMT genotyping identified 89% as TPMT wild type (*1/*1), 10% as TPMT heterozygous and 0.5% as TMPT defective. The overall concordance between genotyping and phenotyping was 95%, while it was 96% among IBD patients (n = 4024). Genotyping would have misclassified 8% of the TPMT defectives as heterozygous as compared to 11% if only TPMT activity had been measured. 11% of the heterozygous patients had a normal TPMT activity (> 8.9 U/ml RBC) and 3% of the TPMT wild-type patients had an intermediate TPMT activity (2.5–8.9 U/ml RBC).ConclusionsThere is a risk for TPMT misclassification when only genotyping or phenotyping is used, but it is not reasonable to check both in all patients. Since TPMT genotyping is the more reliable test, especially in TPMT heterozygotes, we suggest that genotyping should be considered the primary choice for the pre-treatment evaluation of TPMT function before initiation of thiopurine therapy.
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32.
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33.
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34.
  • Hindorf, Ulf, et al. (author)
  • Pharmacogenetics during standardised initiation of thiopurine therapy in inflammatory bowel disease.
  • 2006
  • In: Gut. - : BMJ. - 1468-3288 .- 0017-5749. ; 55:10, s. 1423-1431
  • Journal article (peer-reviewed)abstract
    • Background: Firm recommendations about the way thiopurine drugs are introduced and the use of thiopurine methyltransferase (TPMT) and metabolite measurements during treatment in inflammatory bowel disease (IBD) are lacking. Aim: To evaluate pharmacokinetics and tolerance after initiation of thiopurine treatment with a fixed dosing schedule in patients with IBD. Patients: 60 consecutive patients with Crohn's disease (n = 33) or ulcerative colitis (n = 27) were included in a 20 week open, prospective study. Methods: Thiopurine treatment was introduced using a predefined dose escalation schedule, reaching a daily target dose at week 3 of 2.5 mg azathioprine or 1.25 mg 6-mercaptopurine per kg body weight. TPMT and ITPA genotypes, TPMT activity, TPMT gene expression, and thiopurine metabolites were determined. Clinical outcome and occurrence of adverse events were monitored. Results: 27 patients completed the study per protocol, while 33 were withdrawn (early protocol violation (n = 5), TPMT deficiency (n = 1), thiopurine related adverse events (n = 27)); 67% of patients with adverse events tolerated long term treatment on a lower dose (median 1.32 mg azathioprine/kg body weight). TPMT activity did not change during the 20 week course of the study but a significant decrease in TPMT gene expression was found (TPMT/huCYC ratio; p = 0.02). Patients with meTIMP concentrations > 11 450 pmol/8 x 10(8) red blood cells during steady state at week 5 had an increased risk of developing myelotoxicity (odds ratio = 45.0; p = 0.015). Conclusions: After initiation of thiopurine treatment using a fixed dosing schedule, no general induction of TPMT enzyme activity occurred, though TPMT gene expression decreased. The development of different types of toxicity was unpredictable, but we found that measurement of meTIMP early in the steady state phase helped to identify patients at risk of developing myelotoxicity.
  •  
35.
  • Hindorf, Ulf, et al. (author)
  • Pharmacogenetics during standardised initiation of thiopurine treatment in inflammatory bowel disease
  • 2006
  • In: Gut. - : BMJ. - 0017-5749 .- 1468-3288. ; 55:10, s. 1423-1431
  • Journal article (peer-reviewed)abstract
    • Background: Firm recommendations about the way thiopurine drugs are introduced and the use of thiopurine methyltransferase (TPMT) and metabolite measurements during treatment in inflammatory bowel disease (IBD) are lacking. Aim: To evaluate pharmacokinetics and tolerance after initiation of thiopurine treatment with a fixed dosing schedule in patients with IBD. Patients: 60 consecutive patients with Crohn's disease (n = 33) or ulcerative colitis (n = 27) were included in a 20 week open, prospective study. Methods: Thiopurine treatment was introduced using a predefined dose escalation schedule, reaching a daily target dose at week 3 of 2.5 mg azathioprine or 1.25 mg 6-mercaptopurine per kg body weight. TPMT and ITPA genotypes, TPMT activity, TPMT gene expression, and thiopurine metabolites were determined. Clinical outcome and occurrence of adverse events were monitored. Results: 27 patients completed the study per protocol, while 33 were withdrawn (early protocol violation (n = 5), TPMT deficiency (n = 1), thiopurine related adverse events (n = 27)), 67% of patients with adverse events tolerated long term treatment on a lower dose (median 1.32 mg azathioprine/kg body weight). TPMT activity did not change during the 20 week course of the study but a significant decrease in TPMT gene expression was found (TPMT/huCYC ratio, p = 0.02). Patients with meTIMP concentrations > 11 450 pmol/8 × 108 red blood cells during steady state at week 5 had an increased risk of developing myelotoxicity (odds ratio = 45.0, p = 0.015). Conclusions: After initiation of thiopurine treatment using a fixed dosing schedule, no general induction of TPMT enzyme activity occurred, though TPMT gene expression decreased. The development of different types of toxicity was unpredictable, but we found that measurement of meTIMP early in the steady state phase helped to identify patients at risk of developing myelotoxicity.
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36.
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37.
  • Holstad, Ylva, et al. (author)
  • Breastfeeding in primiparous women with congenital heart disease : a register study
  • 2024
  • In: International Breastfeeding Journal. - : BMJ Publishing Group Ltd. - 1746-4358. ; 19:1
  • Journal article (peer-reviewed)abstract
    • BackgroundThe number of pregnant women with congenital heart disease (CHD) is rising, and the disease poses increased risks of cardiovascular and obstetric complications during pregnancy, potentially impacting breastfeeding success. This study aimed to investigate breastfeeding in primiparous women with CHD compared to primiparous women without CHD, and to examine potential hindering factors for breastfeeding in women with CHD.MethodsThe data were gathered between 2014 and 2019 and obtained by merging the Swedish Congenital Heart Disease Register (SWEDCON) with the Swedish Pregnancy Register. Primiparous women ≥ 18 years of age with CHD (n = 578) were matched by age and municipality to 3049 women without CHD, giving birth after 22 gestational weeks. Multivariable logistic regression analysis was used to identify factors associated with non-breastfeeding in women with CHD.ResultsFewer women with CHD breastfed than women without CHD two days (94% vs. 97%, p = 0.001) and four weeks after birth (84% vs. 89%, p = 0.006). When all women were analysed, having CHD was associated with non-breastfeeding at both two days and four weeks after birth. For women with CHD, body mass index (BMI) ≥ 30 (OR 3.1; 95% CI 1.4, 7.3), preterm birth (OR 6.4; 95% CI 2.1, 19.0), self-reported history of psychiatric illness (OR 2.4; 95% CI 1.2, 5.1), small for gestational age (OR 4.2; 95% CI 1.4, 12.2), and New York Heart Association Stages of Heart Failure class II − III (OR 6.0; 95% CI 1.4, 26.7) were associated with non-breastfeeding two days after birth. Four weeks after birth, factors associated with non-breastfeeding were BMI ≥ 30 (OR 4.3; 95% CI 2.1, 9.0), self-reported history of psychiatric illness (OR 2.2; 95% CI 1.2, 4.2), and preterm birth (OR 8.9; 95% CI 2.8, 27.9).ConclusionsThe study shows that most women with CHD breastfeed, however, at a slightly lower proportion compared to women without CHD. In addition, factors related to the heart disease were not associated with non-breastfeeding four weeks after birth. Since preterm birth, BMI ≥ 30, and psychiatric illness are associated with non-breastfeeding, healthcare professionals should provide greater support to women with CHD having these conditions.
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38.
  • Holstad, Ylva, et al. (author)
  • Self-rated health in primiparous women with congenital heart disease before, during and after pregnancy : a register study
  • 2023
  • In: Scandinavian Cardiovascular Journal. - : Taylor & Francis. - 1401-7431 .- 1651-2006. ; 58:1
  • Journal article (peer-reviewed)abstract
    • Background: Poor maternal self-rated health in healthy women is associated with adverse neonatal outcomes, but knowledge about self-rated health in pregnant women with congenital heart disease (CHD) is sparse. This study, therefore, investigated self-rated health before, during, and after pregnancy in women with CHD and factors associated with poor self-rated health.Methods: The Swedish national registers for CHD and pregnancy were merged and searched for primiparous women with data on self-rated health; 600 primiparous women with CHD and 3062 women in matched controls. Analysis was performed using descriptive statistics, chi-square test and logistic regression.Results: Women with CHD equally often rated their health as poor as the controls before (15.5% vs. 15.8%, p = .88), during (29.8% vs. 26.8% p = .13), and after pregnancy (18.8% vs. 17.6% p = .46). None of the factors related to heart disease were associated with poor self-rated health. Instead, factors associated with poor self-rated health during pregnancy in women with CHD were ≤12 years of education (OR 1.7, 95%CI 1.2–2.4) and self-reported history of psychiatric illness (OR 12.6, 95%CI 1.4–3.4). After pregnancy, solely self-reported history of psychiatric illness (OR 5.2, 95%CI 1.1–3.0) was associated with poor self-rated health.Conclusion: Women with CHD reported poor self-rated health comparable to controls before, during, and after pregnancy, and factors related to heart disease were not associated with poor self-rated health. Knowledge about self-rated health may guide professionals in reproductive counselling for women with CHD. Further research is required on how pregnancy affects self-rated health for the group in a long-term perspective.
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39.
  • Kuna, P., et al. (author)
  • Once-daily dosing with budesonide/formoterol compared with twice-daily budesonide/formoterol and once-daily budesonide in adults with mild to moderate asthma
  • 2006
  • In: Respiratory Medicine. - : Elsevier BV. - 1532-3064 .- 0954-6111. ; 100:12, s. 2151-2159
  • Journal article (peer-reviewed)abstract
    • Adherence to maintenance therapy is often poor in patients with asthma. Simplifying dosing regimens has the potential to improve both adherence and asthma-retated morbidity. In this 12-week, randomized, double-blind, double-dummy, parattel-group study, 617 patients with mild to moderate persistent asthma (mean forced expiratory volume in 1 s [FEV,] 78.5% predicted) who were not optimally controlled on inhaled corticosteroids (200-500pg/day) were randomized to once-daily budesonide/formoterot (80/4.5 tg, 2 inhalations in the evening), twice-daity budesonide/formoterol (80/4.5 pg, 1 inhalation), or a corresponding dose of budesonide once-daily (200pg, 1 inhalation in the evening). AR patients received budesonide (100pg twice daily) during a 2-week run-in. Changes in mean morning peak expiratory flow (PEF) were similar for od budesonide/formoterol (23.4 l/min) and twice-daily budesonide/formoterot (24.1 l/min), and both were greater than with budesonide (5.5 Unnin; both P < 0.001). Evening PEF, symptom-free days, reliever-free days, and asthma control days were improved with budesonide/ formoterol therapy vs. budesonide (P < 0.05 vs. budesonide for all variables). All treatments were well tolerated. Budesonide/formoterot administered once daily in the evening is a convenient treatment regimen that is as effective in improving asthma control as twice-daily dosing in patients with mild to moderate persistent asthma. (c) 2006 Elsevier Ltd. All rights reserved.
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40.
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41.
  • Lindqvist, Anders, et al. (author)
  • Long-term effects of Ca(2+) on structure and contractility of vascular smooth muscle
  • 1999
  • In: American Journal of Physiology: Cell Physiology. - 1522-1563. ; 277:1, s. 64-73
  • Journal article (peer-reviewed)abstract
    • Culture of dispersed smooth muscle cells is known to cause rapid modulation from the contractile to the synthetic cellular phenotype. However, organ culture of smooth muscle tissue, with maintained extracellular matrix and cell-cell contacts, may facilitate maintenance of the contractile phenotype. To test the influence of culture conditions, structural, functional, and biochemical properties of rat tail arterial rings were investigated after culture. Rings were cultured for 4 days in the absence and presence of 10% FCS and then mounted for physiological experiments. Intracellular Ca(2+) concentration ([Ca(2+)](i)) after stimulation with norepinephrine was similar in rings cultured with and without FCS, whereas force development after FCS was decreased by >50%. The difference persisted after permeabilization with beta-escin. These effects were associated with the presence of vasoconstrictors in FCS and were dissociated from its growth-stimulatory action. FCS treatment increased lactate production but did not affect ATP, ADP, or AMP contents. The contents of actin and myosin were decreased by culture but similar for all culture conditions. There was no effect of FCS on calponin contents or myosin SM1/SM2 isoform composition, nor was there any appearance of nonmuscle myosin. FCS-stimulated rings showed evidence of cell degeneration not found after culture without FCS or with FCS + verapamil (1 microM) to lower [Ca(2+)](i). The decreased force-generating ability after culture with FCS is thus associated with increased [Ca(2+)](i) during culture and not primarily caused by growth-associated modulation of cells from the contractile to the synthetic phenotype.
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42.
  • Lindqvist Appell, Malin, et al. (author)
  • A skewed thiopurine metabolism is a common clinical phenomenon that can be successfully managed with a combination of low-dose azathioprine and allopurinol
  • 2013
  • In: Journal of Crohn's & Colitis. - : Elsevier. - 1873-9946 .- 1876-4479. ; 7:6, s. 510-513
  • Journal article (peer-reviewed)abstract
    • Background and aims: A skewed thiopurine metabolism is a phenomenon associated with both poor treatment response and toxicity. Our aim was to evaluate the frequency of this phenomenon and the relationship to thiopurine methyltransferase (TPMT) function. less thanbrgreater than less thanbrgreater thanMethods: All thiopurine metabolite measurements in adult patients (n=4033) between January 2006 and April 2012 were assessed to evaluate the occurrence of a skewed metabolism and the relationship to TPMT genotype and activity. less thanbrgreater than less thanbrgreater thanResults: A skewed metabolism was observed in 14% of all patients. It only developed in patients with a normal TPMT genotype, but was observed at all TPMT activity levels within the normal range (9.1-24.2 U/ml RBC). Two cases that illustrate typical clinical scenarios of a skewed metabolism and the effect of combination treatment with low-dose azathioprine and allopurinol are presented. less thanbrgreater than less thanbrgreater thanConclusions: A skewed metabolism is a common clinical phenomenon in patients with a normal TPMT function, which can develop at all TPMT activity levels within the normal range. We suggest that metabolite measurements should be considered in patients not responding to treatment and in those with hepatotoxicity or myelotoxicity in order to detect a skewed metabolism, since this phenomenon can be successfully managed by a combination of low-dose azathioprine and allopurinol.
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43.
  • Lindqvist Appell, Malin, 1976-, et al. (author)
  • No induction of thiopurine methyltransferase during thiopurine treatment in inflammatory bowel disease
  • 2006
  • In: Nucleosides, Nucleotides & Nucleic Acids. - : Informa UK Limited. - 1525-7770 .- 1532-2335. ; 25:9-11, s. 1033-1037
  • Journal article (peer-reviewed)abstract
    • The aim of this study was to follow, during standardized initiation of thiopurine treatment, thiopurine methyltransferase (TPMT) gene expression and enzyme activity and thiopurine metabolite concentrations, and to study the role of TPMT and ITPA 94C > A polymorphisms for the development of adverse drug reactions. Sixty patients with ulcerative colitis or Crohn's disease were included in this open and prospective multi-center study. Thiopurine naive patients were prescribed azathioprine (AZA), patients previously intolerant to AZA received 6-mercaptopurine (6-MP). The patients followed a predetermined dose escalation schedule, reaching target dose at Week 3; 2.5 and 1.25 mg/kg body weight for AZA and 6-MP, respectively. The patients were followed every week during Weeks 1-8 from baseline and then every 4 weeks until 20 weeks. TPMT activity and thiopurine metabolites were determined in erythrocytes, TPMT and ITPA genotypes, and TPMT gene expression were determined in whole blood. One homozygous TPMT-deficient patient was excluded. Five non compliant patients were withdrawn during the first weeks. Twenty-seven patients completed the study per protocol; 27 patients were withdrawn because of adverse events. Sixty-seven percent of the withdrawn patients tolerated thiopurines at a lower dose at Week 20. There was no difference in baseline TPMT enzyme activity between individuals completing the study and those withdrawn for adverse events (p = 0.45). A significant decrease in TPMT gene expression (TPMT/huCYC ratio, p = 0.02) was found, however TPMT enzyme activity did not change. TPMT heterozygous individuals had a lower probability of remaining in the study on the predetermined dose (p = 0.039). The ITPA 94C > A polymorphism was not predictive of adverse events (p = 0.35).
  •  
44.
  •  
45.
  • Lindqvist Appell, Malin, 1976-, et al. (author)
  • Thiopurines in inflammatory bowel disease - The role of pharmacogenetics and therapeutic drug monitoring
  • 2006
  • In: Current Pharmacogenomics. - : Bentham Science Publishers Ltd.. - 1570-1603. ; 4:4, s. 285-300
  • Journal article (peer-reviewed)abstract
    • Pharmacogenetics represents the study of variability in drug response due to genetic variations. Inflammatory bowel disease (IBD, i.e. primarily Crohn's disease and ulcerative colitis) is characterized by a chronic or relapsing inflammation of the digestive tract. The thiopurines 6-mercaptopurine (6-MP) and azathioprine (AZA), an imidazol derivative and pro-drug of 6-MP, are widely used in IBD, particularly in Crohn's disease. The metabolism of thiopurines is complex and individually variable. Thiopurine methyltransferase (TPMT) is a key enzyme in this metabolism and exhibits a genetic variability due to a number of variant alleles coding for a defective enzyme. The formation of biologically active thioguanine nucleotides (TGN) and methylated metabolites may vary considerably due to the TPMT activity. Patients with decreased TPMT activity are at increased risk of developing severe side effects if treated with conventional thiopurine doses, due to the accumulation of toxic metabolites. Determination of the TPMT phenotype or genotype is often used to identify individuals with increased risk for adverse events. Twenty-one variant TPMT alleles have been described, of which three are more common than the others. An association between inosine triphosphate pyrophosphatase polymorphisms and adverse events during thiopurine treatment has also been proposed. In this review, the clinical value of TPMT status determination and pharmacological monitoring of thiopurine metabolites are discussed as well as the increased interest in the use of 6-thioguanine, a thiopurine with a less complex metabolism, as an alternative for patients who do not tolerate AZA or 6-MP. It can be concluded that TPMT determination before start of thiopurine therapy is of value to identify individuals with increased risk for adverse reactions due to genetic enzyme deficiency. However, large prospective studies are still needed to evaluate the true benefit of monitoring thiopurine metabolites during thiopurine treatment. © 2006 Bentham Science Publishers Ltd.
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46.
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47.
  • Lindqvist, Ebba K., et al. (author)
  • Personal and family history of immune-related conditions increase the risk of plasma cell disorders : a population-based study
  • 2011
  • In: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 118:24, s. 6284-6291
  • Journal article (peer-reviewed)abstract
    • The associations between immune-related conditions and multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS) have previously been investigated with inconsistent results. In a large population-based study, we identified 19 112 patients with MM, 5403 patients with MGUS, 96 617 matched control subjects, and 262 931 first-degree relatives. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) for the association of MM and MGUS with immune-related conditions by use of logistic regression. A personal history of all infections combined was associated with a significantly increased risk of MM (OR = 1.2; 95% CI, 1.1-1.3), and a personal history of all conditions in the categories infections (OR = 1.6; 95% CI, 1.5-1.7), inflammatory conditions (OR = 1.4; 95% CI, 1.2-1.5), and autoimmune diseases (OR = 2.1; 95% CI, 1.9-2.4) was associated with a significantly increased risk of MGUS. Several specific immune-related conditions elevated the risk of MM and/or MGUS. A family history of autoimmune disease was associated with a significantly increased risk of MGUS (OR = 1.1; 95% CI, 1.00-1.2), but not MM. Our findings suggest that immune-related conditions and/or their treatment are of importance in the etiology of MGUS and possibly MM. The association of both personal and family history of autoimmune disease with MGUS indicates the potential for shared susceptibility for these conditions. (Blood. 2011; 118(24): 6284-6291)
  •  
48.
  • Lindqvist, Per, et al. (author)
  • Are suicides by jumping off bridges preventable? An analysis of 50 cases from Sweden.
  • 2004
  • In: Accident; analysis and prevention. - 0001-4575. ; 36:4, s. 691-4
  • Journal article (peer-reviewed)abstract
    • This is a community-based sequential case series of 50 individuals who committed suicide by jumping from bridges in two regions of Sweden. Of the 50 subjects, 32 were men and 18 women, with a median age of 35 years. At least 40 had psychiatric problems. The frequency of suicide was highest during the summer months and during the weekends. A total of 27 bridges were used, with a total length of just under 9 km. Three bridges accounted for almost half of all suicides. Limiting the availability of one method of committing suicide is reported to reduce the overall suicide rate; why suicide and injury suicide preventive measures might be considered. Since this study demonstrates that few bridges attract suicide candidates, this injury mechanism needs to be acknowledged by the road system owners and included in the safety work.
  •  
49.
  • Lindqvist, Per, et al. (author)
  • Asynchronous normal regional left ventricular function assessed by speckle tracking echocardiography : appearances can be deceptive
  • 2009
  • In: International Journal of Cardiology. - : Elsevier. - 0167-5273 .- 1874-1754. ; 134:2, s. 195-200
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Speckle tracking echocardiography (STE) is an angle independent method with high temporal resolution, which offers quantification of regional left ventricular (LV) wall motion. We studied radial and longitudinal LV wall motion by STE in healthy subjects with normal wall motion analysis (WMA) by eye-balling. MATERIALS AND METHODS: Eighteen healthy subjects were studied. We acquired parasternal short and apical long axis projections to determine the basal, mid and apical radial and longitudinal functions. At each level we measured; (I) radial and longitudinal peak displacement and displacement at aortic valve closure (AVC) and (II) the time interval from the Q-wave to the AVC and peak displacement. RESULTS: WMA indicated normal wall motion in all subjects. The mean peak radial displacement varied in different segments (range 3.9-9.8 mm) with highest values in the mid-level (6.9+/-1.5 mm), compared to basal level (5.9+/-1.0 mm, p<0.01) and apical level (5.4+/-1.0 mm, p<0.001). The time from Q-wave to AVC was 393 ms and in 89% of the analysed segments peak radial displacement occurred after AVC, thus mean peak radial displacement occurred 60 ms after AVC. The peak longitudinal amplitude was more synchronous with respect to AVC and with the highest amplitudes found in the two basal segments. CONCLUSIONS: In normal LV function, significant differences in peak displacement exist between segments at various LV levels using STE. In addition, in early diastole, significant discrepancy occurs between radial and longitudinal time of peak displacement, suggesting a shape change. Finally, while radial displacement was highest at mid-cavity level longitudinal displacement was highest at basal level.
  •  
50.
  • Lindqvist, Pelle G, et al. (author)
  • [Vasa praevia test can save lives in Swedish maternity wards]
  • 2011
  • In: Läkartidningen. - 0023-7205 .- 1652-7518. ; 108:4, s. 150-151
  • Journal article (peer-reviewed)abstract
    • Vasa praevia bleeding is a rare (1:4000) obstetric complication. It is associated with a high risk of fetal death (30% to 70%), but is harmless for the mother. After an investigation of the fatal outcome of a case of vasa praevia that was judged to have been avoidable, the Swedish National Board of Health and Welfare determined there is methodology available for the diagnosis of fetal (i.e., vasa praevia) bleeding. They concluded that such “methodology should be introduced in all Swedish maternity wards” and subsequently contacted the Swedish Association of Obstetrics and Gynecology (SFOG) seeking national guidelines in this matter.
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