| 1. |
- Wuttke, Matthias, et al.
(författare)
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A catalog of genetic loci associated with kidney function from analyses of a million individuals
- 2019
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Ingår i: Nature Genetics. - : NATURE PUBLISHING GROUP. - 1061-4036 .- 1546-1718. ; 51:6, s. 957-972
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Tidskriftsartikel (refereegranskat)abstract
- Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through transancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these,147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.
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| 2. |
- Ahrne, Göran, et al.
(författare)
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Akademiskt skrivande
- 2011. - 1
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Ingår i: Handbok i kvalitativa metoder. - 9789147094462
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 3. |
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| 4. |
- Landmesser, Ulf, et al.
(författare)
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Cost-effectiveness of proprotein convertase subtilisin/kexin type 9 inhibition with evolocumab in patients with a history of myocardial infarction in Sweden
- 2022
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Ingår i: European Heart Journal - Quality of Care and Clinical Outcomes. - : Oxford University Press (OUP). - 2058-5225 .- 2058-1742. ; 8:1, s. 31-38
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Tidskriftsartikel (refereegranskat)abstract
- Aims: To assess the cost-effectiveness of proprotein convertase subtilisin/kexin type 9 inhibition with evolocumab added to standard-of-care lipid-lowering treatment [maximum tolerated dose (MTD) of statin and ezetimibe] in Swedish patients with a history of myocardial infarction (MI).Methods and results: Cost-effectiveness was evaluated using a Markov model based on Swedish observational data on cardiovascular event rates and efficacy from the FOURIER trial. Three risk profiles were considered: recent MI in the previous year; history of MI with a risk factor; and history of MI with a second event within 2 years. For each population, three minimum baseline low-density lipoprotein cholesterol (LDL-C) levels were considered: 2.5 mmol/L (≈100 mg/dL), based on the current reimbursement recommendation in Sweden; 1.8 mmol/L (≈70 mg/dL), based on 2016 ESC/EAS guidelines; and 1.4 mmol/L (≈55 mg/dL), or 1.0 mmol/L (≈40 mg/dL) for MI with a second event, based on 2019 ESC/EAS guidelines. Proprotein convertase subtilisin/kexin type 9 inhibition with evolocumab was associated with increased quality-adjusted life-years and costs vs. standard-of-care therapy. Incremental cost-effectiveness ratios (ICERs) were below SEK700 000 (∼€66 500), the generally accepted willingness-to-pay threshold in Sweden, for minimum LDL-C levels of 2.3 (recent MI), 1.7 (MI with a risk factor), and 1.7 mmol/L (MI with a second event). Sensitivity analyses demonstrated that base-case results were robust to changes in model parameters.Conclusion: Proprotein convertase subtilisin/kexin type 9 inhibition with evolocumab added to MTD of statin and ezetimibe may be considered cost-effective at its list price for minimum LDL-C levels of 1.7–2.3 mmol/L, depending on risk profile, with ICERs below the accepted willingness-to-pay threshold in Sweden.
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| 5. |
- Manfredini, Daniele, et al.
(författare)
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Standardised Tool for the Assessment of Bruxism
- 2024
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Ingår i: Journal of Oral Rehabilitation. - : John Wiley & Sons. - 1365-2842 .- 0305-182X. ; 51:1, s. 29-58
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Forskningsöversikt (refereegranskat)abstract
- Objective: This paper aims to present and describe the Standardised Tool for the Assessment of Bruxism (STAB), an instrument that was developed to provide a multidimensional evaluation of bruxism status, comorbid conditions, aetiology and consequences.Methods: The rationale for creating the tool and the road map that led to the selection of items included in the STAB has been discussed in previous publications.Results: The tool consists of two axes, specifically dedicated to the evaluation of bruxism status and consequences (Axis A) and of bruxism risk and etiological factors and comorbid conditions (Axis B). The tool includes 14 domains, accounting for a total of 66 items. Axis A includes the self-reported information on bruxism status and possible consequences (subject-based report) together with the clinical (examiner report) and instrumental (technology report) assessment. The Subject-Based Assessment (SBA) includes domains on Sleep Bruxism (A1), Awake Bruxism (A2) and Patient's Complaints (A3), with information based on patients' self-report. The Clinically Based Assessment (CBA) includes domains on Joints and Muscles (A4), Intra- and Extra-Oral Tissues (A5) and Teeth and Restorations (A6), based on information collected by an examiner. The Instrumentally Based Assessment (IBA) includes domains on Sleep Bruxism (A7), Awake Bruxism (A8) and the use of Additional Instruments (A9), based on the information gathered with the use of technological devices. Axis B includes the self-reported information (subject-based report) on factors and conditions that may have an etiological or comorbid association with bruxism. It includes domains on Psychosocial Assessment (B1), Concurrent Sleep-related Conditions Assessment (B2), Concurrent Non-Sleep Conditions Assessment (B3), Prescribed Medications and Use of Substances Assessment (B4) and Additional Factors Assessment (B5). As a rule, whenever possible, existing instruments, either in full or partial form (i.e. specific subscales), are included. A user's guide for scoring the different items is also provided to ease administration.Conclusions: The instrument is now ready for on-field testing and further refinement. It can be anticipated that it will help in collecting data on bruxism in such a comprehensive way to have an impact on several clinical and research fields.
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| 6. |
- Saxena, Richa, et al.
(författare)
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Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels
- 2007
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 316:5829, s. 1331-1336
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Tidskriftsartikel (refereegranskat)abstract
- New strategies for prevention and treatment of type 2 diabetes (T2D) require improved insight into disease etiology. We analyzed 386,731 common single-nucleotide polymorphisms (SNPs) in 1464 patients with T2D and 1467 matched controls, each characterized for measures of glucose metabolism, lipids, obesity, and blood pressure. With collaborators (FUSION and WTCCC/UKT2D), we identified and confirmed three loci associated with T2D - in a noncoding region near CDKN2A and CDKN2B, in an intron of IGF2BP2, and an intron of CDKAL1 - and replicated associations near HHEX and in SLC30A8 found by a recent whole-genome association study. We identified and confirmed association of a SNP in an intron of glucokinase regulatory protein (GCKR) with serum triglycerides. The discovery of associated variants in unsuspected genes and outside coding regions illustrates the ability of genome-wide association studies to provide potentially important clues to the pathogenesis of common diseases.
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| 7. |
- Svensson, Akiko Kishi, et al.
(författare)
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Incident diabetes mellitus may explain the association between sleep duration and incident coronary heart disease
- 2018
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 61:2, s. 331-341
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Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis: Sleep duration is a risk factor for incident diabetes mellitus and CHD. The primary aim of the present study was to investigate, in sex-specific analyses, the role of incident diabetes as the possible biological mechanism for the reported association between short/long sleep duration and incident CHD. Considering that diabetes is a major risk factor for CHD, we hypothesised that any association with sleep duration would not hold for cases of incident CHD occurring before incident diabetes (‘non-diabetes CHD’) but would hold true for cases of incident CHD following incident diabetes (‘diabetes-CHD’). Methods: A total of 6966 men and 9378 women aged 45–73 years from the Malmö Diet Cancer Study, a population-based, prospective cohort, who had answered questions on habitual sleep duration and did not have a history of prevalent diabetes or CHD were included in the analyses. Incident cases of diabetes and CHD were identified using national registers. Sex-specific Cox proportional hazards regression models were stratified by BMI and adjusted for known covariates of diabetes and CHD. Results: Mean follow-up times for incident diabetes (n = 1137/1016 [men/women]), incident CHD (n = 1170/578), non-diabetes CHD (n = 1016/501) and diabetes-CHD (n = 154/77) were 14.2–15.2 years for men, and 15.8–16.5 years for women. In men, short sleep duration (< 6 h) was associated with incident diabetes (HR 1.35, 95% CI 1.01, 1.80), CHD (HR 1.41, 95% CI 1.06, 1.89) and diabetes-CHD (HR 2.34, 95% CI 1.20, 4.55). Short sleep duration was not associated with incident non-diabetes CHD (HR 1.35, 95% CI 0.98, 1.87). Long sleep duration (≥ 9 h) was associated with incident diabetes (HR 1.37, 95% CI 1.03, 1.83), CHD (HR 1.33, 95% CI 1.01, 1.75) and diabetes-CHD (HR 2.10, 95% CI 1.11, 4.00). Long sleep duration was not associated with incident non-diabetes CHD (HR 1.33, 95% CI 0.98, 1.80). In women, short sleep duration was associated with incident diabetes (HR 1.53, 95% CI 1.16, 2.01), CHD (HR 1.46, 95% CI 1.03, 2.07) and diabetes-CHD (HR 2.88, 95% CI 1.37, 6.08). Short sleep duration was not associated with incident non-diabetes CHD (HR 1.29, 95% CI 0.86, 1.93). Conclusions/interpretation: The associations between sleep duration and incident CHD directly reflect the associations between sleep duration and incident diabetes. Incident diabetes may thus be the explanatory mechanism for the association between short and long sleep duration and incident CHD.
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| 8. |
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| 9. |
- Svensson, Peter, et al.
(författare)
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Multidisciplinär kurs i akutmedicin ger ST-läkare större säkerhet
- 2002
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Ingår i: Läkartidningen. - 0023-7205. ; 99:45, s. 4490-4490
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Tidskriftsartikel (refereegranskat)abstract
- Lack of courses in emergency medicine for doctors under training is currently a problem in Sweden. Only 10 percent will have these courses early under their internship. The University hospital in Malmoe has therefore decided to create a course for doctors under training and to offer it early in their education. The curriculum is based on a problem-based learning concept using a modified case methodology that has been used since the 1920's at Harvard Business school in Boston. The course integrates doctors from different specialties with experienced nurses from the emergency ward. The five day course comprises; three theoretical days where cases from the emergency room are discussed with the case methodology, followed by two days of practical training. Our results from 100 participants over a period of two years is very encouraging, over 85 percent of the participants were very satisfied with the course. The multidisciplinary discussion about different cases was much appreciated. Our experience of this problem-based learning concept is very good, since it promotes deep rather than surface learning and promotes an in-depth collaboration between disciplines.
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| 10. |
- Svensson, Peter, et al.
(författare)
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Om samhällsvetenskapens natur
- 2022. - 3
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Ingår i: Handbok i kvalitativa metoder. - 9789147140077 ; , s. 17-23
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 11. |
- Svensson, Peter, et al.
(författare)
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Teorins roll i kvalitativ forskning
- 2011. - 1
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Ingår i: Handbok i kvalitativa metoder. - 9789147094462
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 12. |
- Svensson, Thomas, et al.
(författare)
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Plasma concentration of Caspase-8 is associated with short sleep duration and the risk of incident diabetes mellitus
- 2018
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 103:4, s. 1592-1600
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Tidskriftsartikel (refereegranskat)abstract
- Context: The biological mechanism for the association between sleep duration and incident diabetes mellitus (DM) is unclear. Sleep duration and Caspase-8, a marker of apoptotic activity, have both been implicated in beta cell function.Objective: To investigate the associations between sleep duration and plasma Caspase-8, and incident DM, respectively.Design: Prospective cohort study.Setting: The Malmö Diet and Cancer (MDC) Study is a population-based, prospective study run in the city of Malmö, Sweden.Participants: 4023 individuals from the MDC Study aged 45-68 years at baseline without a history of prevalent DM, and with information on habitual sleep duration.Main outcomes: Incident DM.Results: Mean follow-up time was 17.8 years. Sleep duration was the only behavioural variable significantly associated with plasma Caspase-8. Plasma Caspase-8 was significantly associated with incident DM per standard deviation of its transformed continuous form (hazard ratio [HR]= 1.24, 95% confidence interval [CI] 1.13-1.36), and when dichotomized into high (quartile 4) (HR=1.44, 95%CI: 1.19-1.74) compared to low (quartiles 1-3) concentrations. Caspase-8 interacted with sleep duration; compared to 7-8 hours of sleep and low plasma Caspase-8, individuals with high plasma Caspase-8 and sleep duration <6 hours (HR=3.54, 95%CI: 2.12-5.90), 6-7 hours (HR=1.81, 95%CI: 1.24-2.65), and 8-9 hours (HR=1.54, 95%CI: 1.09-2.18) were at significantly increased risks of incident DM.Conclusions: Sleep duration is associated with plasma Caspase-8. Caspase-8 independently predicts DM years before disease onset and modifies the effect of sleep duration on incident DM. Future studies should investigate if change of sleep duration modifies plasma concentrations of Caspase-8.
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| 13. |
- Zamora, Juan Carlos, et al.
(författare)
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Considerations and consequences of allowing DNA sequence data as types of fungal taxa
- 2018
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Ingår i: IMA Fungus. - : INT MYCOLOGICAL ASSOC. - 2210-6340 .- 2210-6359. ; 9:1, s. 167-185
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Tidskriftsartikel (refereegranskat)abstract
- Nomenclatural type definitions are one of the most important concepts in biological nomenclature. Being physical objects that can be re-studied by other researchers, types permanently link taxonomy (an artificial agreement to classify biological diversity) with nomenclature (an artificial agreement to name biological diversity). Two proposals to amend the International Code of Nomenclature for algae, fungi, and plants (ICN), allowing DNA sequences alone (of any region and extent) to serve as types of taxon names for voucherless fungi (mainly putative taxa from environmental DNA sequences), have been submitted to be voted on at the 11th International Mycological Congress (Puerto Rico, July 2018). We consider various genetic processes affecting the distribution of alleles among taxa and find that alleles may not consistently and uniquely represent the species within which they are contained. Should the proposals be accepted, the meaning of nomenclatural types would change in a fundamental way from physical objects as sources of data to the data themselves. Such changes are conducive to irreproducible science, the potential typification on artefactual data, and massive creation of names with low information content, ultimately causing nomenclatural instability and unnecessary work for future researchers that would stall future explorations of fungal diversity. We conclude that the acceptance of DNA sequences alone as types of names of taxa, under the terms used in the current proposals, is unnecessary and would not solve the problem of naming putative taxa known only from DNA sequences in a scientifically defensible way. As an alternative, we highlight the use of formulas for naming putative taxa (candidate taxa) that do not require any modification of the ICN.
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| 14. |
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| 15. |
- Baldvinsdóttir, Bryndís, et al.
(författare)
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Adverse events during endovascular treatment of ruptured aneurysms : A prospective nationwide study on subarachnoid hemorrhage in Sweden
- 2023
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Ingår i: BRAIN AND SPINE. - : Elsevier. - 2772-5294. ; 3
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: A range of adverse events (AEs) may occur in patients with subarachnoid hemorrhage (SAH). Endovascular treatment is commonly used to prevent aneurysm re-rupture.Research question: The aim of this study was to identify AEs related to endovascular treatment, analyze risk factors for AEs and how AEs affect patient outcome.Material and methods: Patients with aneurysmal SAH admitted to all neurosurgical centers in Sweden during a 3.5-year period (2014-2018) were prospectively registered. AEs related to endovascular aneurysm treatment were thromboembolic events, aneurysm re-rupture, vessel dissection and puncture site hematoma. Potential risk factors for the AEs were analyzed using multivariate logistic regression. Functional outcome was assessed at one year using the extended Glasgow outcome scale.Results: In total, 1037 patients were treated for ruptured aneurysms. Of which, 715 patients were treated with endovascular occlusion. There were 115 AEs reported in 113 patients (16%). Thromboembolic events were noted in 78 patients (11%). Aneurysm re-rupture occurred in 28 (4%), vessel dissection in 4 (0.6%) and puncture site hematoma in 5 (0.7%). Blister type aneurysm, aneurysm smaller than 5 mm and endovascular techniques other than coiling were risk factors for treatment-related AEs. At follow-up, 230 (32%) of the patients had unfavorable outcome. Patients suffering intraprocedural aneurysm re-rupture were more likely to have unfavorable outcome (OR 6.9, 95% CI 2.3-20.9).Discussion and conclusion: Adverse events related to endovascular occlusion of a ruptured aneurysm were seen in 16% of patients. Aneurysm re-rupture during endovascular treatment was associated with increased risk of unfavorable functional outcome.
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| 16. |
- Calling, Susanna, et al.
(författare)
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Lung function, respiratory symptoms and incident venous thromboembolism during a 44-year follow-up
- 2023
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Ingår i: Thrombosis Update. - Oxford : Elsevier. - 2666-5727. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Background: Chronic obstructive pulmonary disease (COPD) and infections are risk factors for venous thromboembolism (VTE), but the reasons behind the associations are not fully known. Few studies have investigated whether lung function and respiratory symptoms in individuals without COPD are associated with VTE. Objectives: To study the incidence of VTE in individuals without COPD and other major VTE risk factors, in relation to baseline lung function and respiratory symptoms, through a 44-year follow-up prospective cohort study. Methods: As part of a health screening program, a total of 20,253 men and 7361 women underwent a baseline examination from 1974 to 1992, including a spirometry test and a self-administered questionnaire about respiratory symptoms, e.g., chronic bronchitis, cough, phlegm, and dyspnoea. Lung function was assessed through quartiles of forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC). Through linkage with national registers, all individuals were followed for incidence of VTE. Results: Respiratory symptoms (cough and dyspnoea) at baseline were associated with an increased risk of incident VTE in women after adjustments for age, height, BMI, smoking status, varicose veins, and FEV1/FVC. The adjusted hazard ratio in relation to chronic bronchitis was 1.57 (95% confidence interval 1.17–2.11). Poor lung function was not associated with an increased risk of VTE after adjustments for potential confounders. Conclusion: Women with respiratory symptoms of cough and dyspnoea without COPD have an increased risk of VTE, independent of lung function and major VTE risk factors. Further studies are needed to confirm the association and to study the clinical applicability of the results. © 2023 The Authors
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| 17. |
- Fresia, Maria, et al.
(författare)
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Use case characterization, KPIs and preferred suitable frequency ranges for future 5G systems between 6 GHz and 100 GHz
- 2015
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- In this deliverable use cases and KPIs of interest for mmMAGIC are characterized. Eight usecases suitable for 5G systems operating in the range 6-100GHz are identified in terms ofrequirements. In particular, the following use cases are analyzed: Media on demand; Cloudservices; Dense urban society with distributed crowds; Smart offices; Immersive 5G earlyexperience in targeting hot spots; 50+Mbps everywhere; Moving hot spots; Tactileinternet/video augmented robotic control and remote-robot manipulation surgery. For each ofthe use cases, the more critical KPIs are identified and the gap from the current technologyis also described.An analysis of frequency ranges for future 5G systems between 6 GHz and 100 GHz is reported. A frequency assessment study is conducted in order to compare the frequency ranges for the suitability of delivering key KPIs.
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| 18. |
- Gustavsson, Anders, et al.
(författare)
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Cost of disorders of the brain in Europe 2010.
- 2011
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Ingår i: European Neuropsychopharmacology. - Amsterdam : Elsevier BV. - 0924-977X .- 1873-7862. ; 21:10, s. 718-79
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The spectrum of disorders of the brain is large, covering hundreds of disorders that are listed in either the mental or neurological disorder chapters of the established international diagnostic classification systems. These disorders have a high prevalence as well as short- and long-term impairments and disabilities. Therefore they are an emotional, financial and social burden to the patients, their families and their social network. In a 2005 landmark study, we estimated for the first time the annual cost of 12 major groups of disorders of the brain in Europe and gave a conservative estimate of €386 billion for the year 2004. This estimate was limited in scope and conservative due to the lack of sufficiently comprehensive epidemiological and/or economic data on several important diagnostic groups. We are now in a position to substantially improve and revise the 2004 estimates. In the present report we cover 19 major groups of disorders, 7 more than previously, of an increased range of age groups and more cost items. We therefore present much improved cost estimates. Our revised estimates also now include the new EU member states, and hence a population of 514 million people.AIMS: To estimate the number of persons with defined disorders of the brain in Europe in 2010, the total cost per person related to each disease in terms of direct and indirect costs, and an estimate of the total cost per disorder and country.METHODS: The best available estimates of the prevalence and cost per person for 19 groups of disorders of the brain (covering well over 100 specific disorders) were identified via a systematic review of the published literature. Together with the twelve disorders included in 2004, the following range of mental and neurologic groups of disorders is covered: addictive disorders, affective disorders, anxiety disorders, brain tumor, childhood and adolescent disorders (developmental disorders), dementia, eating disorders, epilepsy, mental retardation, migraine, multiple sclerosis, neuromuscular disorders, Parkinson's disease, personality disorders, psychotic disorders, sleep disorders, somatoform disorders, stroke, and traumatic brain injury. Epidemiologic panels were charged to complete the literature review for each disorder in order to estimate the 12-month prevalence, and health economic panels were charged to estimate best cost-estimates. A cost model was developed to combine the epidemiologic and economic data and estimate the total cost of each disorder in each of 30 European countries (EU27+Iceland, Norway and Switzerland). The cost model was populated with national statistics from Eurostat to adjust all costs to 2010 values, converting all local currencies to Euro, imputing costs for countries where no data were available, and aggregating country estimates to purchasing power parity adjusted estimates for the total cost of disorders of the brain in Europe 2010.RESULTS: The total cost of disorders of the brain was estimated at €798 billion in 2010. Direct costs constitute the majority of costs (37% direct healthcare costs and 23% direct non-medical costs) whereas the remaining 40% were indirect costs associated with patients' production losses. On average, the estimated cost per person with a disorder of the brain in Europe ranged between €285 for headache and €30,000 for neuromuscular disorders. The European per capita cost of disorders of the brain was €1550 on average but varied by country. The cost (in billion €PPP 2010) of the disorders of the brain included in this study was as follows: addiction: €65.7; anxiety disorders: €74.4; brain tumor: €5.2; child/adolescent disorders: €21.3; dementia: €105.2; eating disorders: €0.8; epilepsy: €13.8; headache: €43.5; mental retardation: €43.3; mood disorders: €113.4; multiple sclerosis: €14.6; neuromuscular disorders: €7.7; Parkinson's disease: €13.9; personality disorders: €27.3; psychotic disorders: €93.9; sleep disorders: €35.4; somatoform disorder: €21.2; stroke: €64.1; traumatic brain injury: €33.0. It should be noted that the revised estimate of those disorders included in the previous 2004 report constituted €477 billion, by and large confirming our previous study results after considering the inflation and population increase since 2004. Further, our results were consistent with administrative data on the health care expenditure in Europe, and comparable to previous studies on the cost of specific disorders in Europe. Our estimates were lower than comparable estimates from the US.DISCUSSION: This study was based on the best currently available data in Europe and our model enabled extrapolation to countries where no data could be found. Still, the scarcity of data is an important source of uncertainty in our estimates and may imply over- or underestimations in some disorders and countries. Even though this review included many disorders, diagnoses, age groups and cost items that were omitted in 2004, there are still remaining disorders that could not be included due to limitations in the available data. We therefore consider our estimate of the total cost of the disorders of the brain in Europe to be conservative. In terms of the health economic burden outlined in this report, disorders of the brain likely constitute the number one economic challenge for European health care, now and in the future. Data presented in this report should be considered by all stakeholder groups, including policy makers, industry and patient advocacy groups, to reconsider the current science, research and public health agenda and define a coordinated plan of action of various levels to address the associated challenges.RECOMMENDATIONS: Political action is required in light of the present high cost of disorders of the brain. Funding of brain research must be increased; care for patients with brain disorders as well as teaching at medical schools and other health related educations must be quantitatively and qualitatively improved, including psychological treatments. The current move of the pharmaceutical industry away from brain related indications must be halted and reversed. Continued research into the cost of the many disorders not included in the present study is warranted. It is essential that not only the EU but also the national governments forcefully support these initiatives.
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| 19. |
- Gustavsson, Carl Gunnar, et al.
(författare)
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Thrombotic occlusion of all left coronary branches in a young woman with severe ulcerative colitis
- 2011
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Ingår i: ISRN Cardiology. - : Hindawi Limited. - 2090-5580 .- 2090-5599.
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Tidskriftsartikel (refereegranskat)abstract
- Background. The thrombosis risk is increased in active ulcerative colitis. The limited number of reported complications have predominantly been cerebrovascular but other vessel territories may also be affected. Patient. During a severe attack of ulcerative colitis a 37-year-old woman suffered occlusion of all left coronary artery branches. Serial angiographies showed progressive recanalisation of the coronary arteries during anticoagulation, but no atherosclerotic stenosis. The cause of infarction was thus considered to be an extensive coronary thrombosis. However, a large battery of blood tests failed to identify any procoagulant abnormality. Conclusion. Evidence is now accumulating that the increased thrombosis risk also may involve the coronary arteries, even in young patients. To the best of our knowledge this is the third reported case ofmyocardial infarction despite angiographically normal coronary arteries in a patient with active ulcerative colitis. The extent of affected myocardiumwas in this case exceptionally large.
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| 20. |
- Hagmarker, Linn, et al.
(författare)
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Characterisation of a planar dosimetry method estimating the absorbed dose to the bone marrow during 177Lu-DOTATATE treatment
- 2016
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Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer. - 1619-7070 .- 1619-7089.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Aim: An image based method for bone marrow dosimetry, earlier presented by our research group, has shown a significant correlation between the absorbed dose to the bone marrow and haematological toxicity in 177Lu-DOTATATE treatment. The aim of this study was to further evaluate and optimise the method. Materials and Methods: 46 patients with advanced neuroendocrine tumours were treated with 177Lu -DOTATATE on 2-6 occasions. The patients were evaluated using the 4 planar gamma camera images collected at 2, 24, 48 and 168 hours after injection. The whole body was divided into a high- and a low uptake compartment, using a threshold based segmentation tool in the image platform PhONSAi, developed in-house. The segmentation tool starts by including the highest uptake focus and then gradually includes foci with lower and lower uptakes until a threshold is reached where the number of foci escalates. The threshold determines the proportion of the foci that is included in the two compartments. Visual inspection was used to determine the threshold valuewhere all high uptake tissues (i.e. kidney, spleen, liver and tumours) were included in the high uptake compartment. For thresholds around this value the activity in the two compartments was determined by the conjugate view method and the bonemarrow dose was calculated as a sum of the self and cross dose in the low uptake compartment and the cross dose from the high uptake compartment. Results: The visual analysis implies a threshold value of 10%of the maximum number of foci. A correlation was found between the absorbed bone marrow dose and haematological toxicity with p-values ranging from 0.001 to 0.02 for thresholds between 2 % and 25 %, the strongest correlation was found at 15 %. The mean absorbed bone marrow dose were 0.20-0.22 Gy per 7.4 GBq for threshold values between 10-25 %, and increased to 0.28 Gy for the lower values. No significant difference was observed in coefficient of variation (8.2-8.7 %) for the individual mean absorbed doses when varying the threshold value. Conclusion: The individual variation in absorbed dose is maintained at a low level when varying the threshold value for the determination of the compartment sizes. This implies that the method is stable for estimation of bone marrow doses and its correlation to haematological toxicity.
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| 21. |
- Hagmarker, Linn, et al.
(författare)
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Evaluation of planar versus hybrid SPECT image methodology for bone marrow dosimetry during 177Lu-DOTATATE treatments reveals the obstacles with bone marrow metastases and cross-irradiation for the SPECT activity concentration quantification
- 2018
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Ingår i: 31st Annual Congress of the European Association of Nuclear Medicine (EANM’18). 13-17 October, Dusseldorf, Germany.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Introduction. The aim of this study is to compare the recently developed planar image-based method for bone marrow dosimetry with a hybrid method using SPECT/CT imaging at 24 h.p.i. of 177Lu-DOTATATE. Predictive ability of the methods is compared by investigating correlations of determined absorbed bone marrow dose, with haematological toxicity during the course of four treatment cycles. The aim is also to investigate the activity distribution in the vertebral column, and how the hybrid methodology can be optimized. Methods and Materials. 45 patients with advanced neuroendocrine tumours treated with 177Lu-DOTATATE at Sahlgrenska University Hospital in 2011-2016 (ILUMINET-study, EUDRACT nr 2011-etc) were included in this study. Absorbed bone marrow doses were calculated as the sum of the cross-doses from high-uptake organs and the remainder of the body, and the self-dose. Cross-doses were determined by time-activity curves created using planar images and a two-compartment method in the image platform PhONSAi. The self-dose was calculated using the time-activity concentration curve for the remainder of the body adjusted with the activity concentration determined in spheres placed in the vertebral bodies in SPECT-images. To improve recovery and reduce cross-irradiation of false counts in the SPECT-image, we utilized the Monte Carlo based reconstruction code SARec. Three activity concentrations were calculated to represent the activity concentration in the bone marrow; one mean (mean SPECT) and one median (median SPECT) activity concentration based on all visible vertebras and one where vertebras enclosing metastases were manually excluded (w/o Mets SPECT). Results. The planar method, the hybrid methods mean SPECT, median SPECT, and w/o Mets SPECT, yielded absorbed bone marrow doses after treatment cycle one at 0.19 (0.12-0.32), 0.35 (0.12-1.25), 0.29 (0.11-0.92) and 0.29 (0.15-0.81) Gy/7.4 GBq, respectively. A significant dose-response relationship was established after treatment cycle one between decreased platelet counts and absorbed bone marrow dose using the planar method (p=0.025, r=-0.16). With hybrid methods, a significant correlation was firstly found after treatment cycle two between absorbed dose and decreased platelet counts using median SPECT (p=0.018, r=-0.35). Conclusion. Early significant dose-response relationships were established. Despite using SARec-reconstructed SPECT-imaging for specific measurement of activity concentration in bone marrow cavities, the hybrid methods were not able to perform better than the planar method. The hybrid methods yielded higher absorbed bone marrow doses compared to the planar method as both bone metastases and cross-irradiation will influence the activity quantification. Further studies on minimizing influence of bone metastases and cross-irradiation are on-going.
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| 22. |
- Hemmingsson, Jens, 1986, et al.
(författare)
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Autoradiography and biopsy measurements of a resected hepatocellular carcinoma treated with 90 yttrium radioembolization demonstrate large absorbed dose heterogeneities
- 2018
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Ingår i: Advances in Radiation Oncology. - : Elsevier BV. - 2452-1094. ; 3:3, s. 439-446
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Tidskriftsartikel (refereegranskat)abstract
- © 2018 The Authors Purpose: Radioembolization is an alternative palliative treatment for hepatocellular carcinoma. Here, we examine the uptake differences between tumor tissue phenotypes and present a cross-section of the absorbed dose throughout a liver tissue specimen. Methods and materials: A patient with hepatocellular carcinoma was treated with90Y radioembolization followed by liver tissue resection. Gamma camera images and autoradiographs were collected and biopsy tissue samples were analyzed using a gamma well counter and light microscopy. Results: An analysis of 25 punched biopsy tissue samples identified 4 tissue regions: Normal tissue, viable tumor tissue with and without infarcted areas, and tumor areas with postnecrotic scar tissue. Autoradiography and biopsy tissue sample measurements showed large dose differences between viable and postnecrotic tumor tissue (159 Gy vs 23 Gy). Conclusions: Radioembolization of 90 yttrium with resin microspheres produces heterogeneous-absorbed dose distributions in the treatment of unifocal hepatic malignancies that could not be accurately determined with current gamma camera imaging techniques.
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| 23. |
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| 24. |
- Hugosson, Anna, et al.
(författare)
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A community outbreak of Legionnaires' disease from an industrial cooling tower: assessment of clinical features and diagnostic procedures.
- 2007
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Ingår i: Scandinavian journal of infectious diseases. - : Informa UK Limited. - 0036-5548 .- 1651-1980. ; 39:3, s. 217-24
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Tidskriftsartikel (refereegranskat)abstract
- An outbreak of Legionnaires' disease (LD) occurred in Lidköping, Sweden, in August 2004. A cooling tower was identified as the probable source of infection. During the outbreak period an unexpected 3-6-fold increase in pneumonia patients was noted at the local hospital. During 7 weeks LD was diagnosed in 15 patients by urinary antigen and/or sputum culture. Additionally, 15 LD patients were diagnosed later by serology. Patients with LD were generally younger, more healthy, and more often smokers compared to other pneumonia patients. On admittance they had more severe symptoms with high fever and raised CRP levels, and more often hyponatraemia, gastrointestinal and CNS symptoms. A causative agent besides Legionella was found in 2 patients only. A significant titre rise for Mycoplasma and/or Chlamydophila pneumoniae was found in 13 of 29 tested patients with confirmed LD. We conclude that the clinical diagnosis of LD is difficult and that available diagnostic methods detect only a minority of patients in the acute phase. Therefore in severe pneumonia, empirically targeted therapy should be instituted on clinical grounds irrespective of the results of diagnostic tests. The observation of increased antibody levels for M. and C. pneumoniae suggests an unspecific immune reaction and merits further study.
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| 25. |
- Högberg, Jonas, 1976, et al.
(författare)
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Bremsstrahlung imaging of 90Y microspheres shows poor resemblance with distributions of 99mTc-MAA in liver
- 2010
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Ingår i: Journal of the European Society of Therapeutic Radiology and Oncology. - 0167-8140. ; 94:1, s. 25-26
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- PURPOSE To study the resemblance between the distributions of pre- therapeutic 99mTc-MAA and therapeutic 90Y-microspheres, used for ra- dioembolization of liver tumours, making use of gamma- and bremsstrahlung imaging. Furthermore, to establish the accuracy of this method by compar- isons of spatial resolution and radioactivity, performed on line source in water phantom and on resected tumour and normal liver from patients previously treated with 90Y-microspheres. MATERIALS 3 patients diagnosed with liver tumours and planned for surgery; 1 with hepatocellular carcinoma and 2 with cholangiocarcinoma, were treated with SIRTEX R © 90Y-microspheres after standard diagnostic SPECT/CT imag- ing with 99mTc-MAA. The images acquired with gamma camera were com- pared regarding distributions of radioactivity; gamma radiation from the 99mTc-MAA distributions and bremsstrahlung from the distributions of 90Y- microspheres (the latter with a wide bremsstrahlung energy window). Resec- tions of tumour- and some normal liver tissues were performed on all three patients; the resected tissues were sliced, smaller samples were punched out and the radioactivity was measured with a NaI-detector. Furthermore, autoradiography was performed on some slices. A line source with the in- ner diameter 1 mm was positioned in a cylindrical water phantom with the diameter 20 cm; first the line source was filled with 99mTc, then emptied and filled with 90Y. SPECT/CT imaging was performed on both line source se- tups. The spatial resolutions for both radionuclides were then compared. The results from the imaging comparisons performed on the patients were then evaluated with the complementary radiological methods described above. RESULTS The comparison of images from 99mTc-MAA and 90Y showed a considerable deviance in activity distribution for two of the patients. One ex- ample is shown in the figure, the upper image showing 99mTc-MAA and the lower showing 90Y-microspheres. The moderate difference in spatial resolu- tions for 99mTc and 90Y, (15 vs 18 mm FWHM) confirmed the accuracy of these findings. The other radiological methods did also confirm the macro- scopic activity distribution as shown with bremsstrahlung imaging. CONCLUSIONS Bremsstrahlung imaging is a satisfying and reliable method in showing the actual macroscopic distribution of therapeutic 90Y-microspheres used for radioembolization of liver tumours. The results further demonstrate the need for a better diagnostic method than the one currently used, with 99mTc-MAA, thereby providing a better pre-dosimetry; hopefully with a better selection of patients, regarding tumour regression and a lower risk of liver failure.
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