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  • Liss, Per, et al. (författare)
  • Renal effects of CO2 and iodinated contrast media in patients undergoing renovascular intervention : a prospective, randomized study
  • 2005
  • Ingår i: Journal of Vascular and Interventional Radiology. - 1051-0443 .- 1535-7732. ; 16:1, s. 57-65
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: CO2 gas has been proposed for use instead of iodinated contrast media in angiographic examinations in patients at risk of developing renal failure from contrast media. The influence of intraarterial injection of CO2 with small added amounts of ioxaglate (200 mgI/mL) or ioxaglate alone on renal function in patients with suspected renal artery stenosis was studied in a prospective, randomized study. MATERIALS AND METHODS: One hundred twenty-three patients underwent renovascular intervention (n = 83) and/or renal angiography (n = 40) for suspected renal artery stenosis. Patients with a serum creatinine concentration less than 200 micromol/L (n = 82) were randomized prospectively to receive CO2 with small added amounts of ioxaglate (n = 37) or only ioxaglate (n = 45). Patients with serum creatinine levels greater than 200 micromol/L (n = 41) were not randomized and initially received CO2. Serum creatinine concentrations were measured within 1 day before and 1 day, 2 days, and 2-3 weeks after the procedure. RESULTS: The amount of injected CO2 did not relate to an increase in serum creatinine level. In the randomized groups, and also when the whole patient sample was considered, the amount of injected iodine was significantly correlated (P = .011) with an increase in serum creatinine level and a decrease in estimated creatinine clearance after 2 days. Among the randomized patients, one in the CO2 group and three in the ioxaglate group had a more than 25% increase in serum creatinine level within the first 2 days after the intervention. CONCLUSION: The risk of impairment of renal function is lower after injection of CO2 with small amounts of added ioxaglate compared with injection of a larger amount of ioxaglate alone. The larger the amount of administered iodinated contrast medium, the greater the risk of development of renal failure.
  • Dalin, Frida, et al. (författare)
  • Clinical and immunological characteristics of Autoimmune Addison's disease : a nationwide Swedish multicenter study
  • 2017
  • Ingår i: Journal of Clinical Endocrinology and Metabolism. - Oxford University Press. - 0021-972X .- 1945-7197. ; 102:2, s. 379-389
  • Tidskriftsartikel (refereegranskat)abstract
    • CONTEXT: Studies on clinical and immunological features of Autoimmune Addison's disease (AAD) are needed to understand the disease burden and increased mortality.OBJECTIVE: To provide upgraded data on autoimmune comorbidities, replacement therapy, autoantibody profiles and cardiovascular risk factors.DESIGN, SETTING AND PARTICIPANTS: Cross sectional, population-based study. 660 AAD patients were included utilizing the Swedish Addison Registry (SAR) 2008-2014. When analyzing cardiovascular risk factors, 3,594 individuals from the population-based survey in Northern Sweden, MONICA (MONItoring of Trends and Determinants of CArdiovascular Disease), served as controls.MAIN OUTCOME MEASURE: Prevalence of autoimmune comorbidities and cardiovascular risk factors. Autoantibodies against 13 autoantigens were determined.RESULTS: Sixty percent of the SAR cohort consisted of females. Mean age at diagnosis was significantly higher for females than for males (36.8 vs. 31.1 years). The proportion of 21-hydroxylase autoantibody positive patients was 83% and 62% of patients had one or more associated autoimmune diseases, more frequently coexisting in females (p<0.0001). AAD patients had lower BMI (p<0.0001) and prevalence of hypertension (p=0.027) compared with controls. Conventional hydrocortisone tablets were used by 89% of patients; with the mean dose 28.1±8.5 mg/day. The mean hydrocortisone equivalent dose normalized to body surface was 14.8±4.4 mg/m(2)/day. Higher hydrocortisone equivalent dose was associated with higher incidence of hypertension (p=0.046).CONCLUSIONS: Careful monitoring of AAD patients is warranted to detect associated autoimmune diseases. Contemporary Swedish AAD patients do not have increased prevalence of overweight, hypertension, T2DM or hyperlipidemia. However, high glucocorticoid replacement doses may be a risk factor for hypertension.
  • Johansson, Karl-Axel, et al. (författare)
  • The quality assurance process for the ARTSCAN head and neck study - A practical interactive approach for QA in 3DCRT and IMRT
  • 2008
  • Ingår i: Radiotherapy and Oncology. - Elsevier. - 1879-0887. ; 87:2, s. 290-299
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim: This paper describes the quality assurance (QA) work performed in the Swedish multicenter ARTSCAN (Accelerated RadioTherapy of Squamous cell CArcinomas in the head and Neck) trial to guarantee high quality in a multicenter study which involved modern radiotherapy such as 3DCRT or IMRT. Materials and methods: The study was closed in June 2006 with 750 randomised patients. Radiation therapy-related data for every patient were sent by each participating centre to the QA office where all trial data were reviewed, analysed and stored. In case of any deviation from the protocol, an interactive process was started between the QA office and the local responsible clinician and/or physicist to increase the compliance to the protocol for future randomised patients. Meetings and workshops were held on a regular basis for discussions on various trial-related issues and for the QA office to report on updated results. Results and discussion: This review covers the 734 patients out of a total of 750 who had entered the study. Deviations early in the study were corrected so that the overall compliance to the protocol was very high. There were only negligible variations in doses and dose distributions to target volumes for each specific site and stage. The quality of the treatments was high. Furthermore, an extensive database of treatment parameters was accumulated for future dose-volume vs. endpoint evaluations. Conclusions: This comprehensive QA programme increased the probability to draw firm conclusions from our study and may serve as a concept for QA work in future radiotherapy trials where comparatively small effects are searched for in a heterogeneous tumour population.
  • Barban, Nicola, et al. (författare)
  • Genome-wide analysis identifies 12 loci influencing human reproductive behavior
  • 2016
  • Ingår i: Nature Genetics. - 1061-4036 .- 1546-1718. ; 48:12, s. 1462-1472
  • Tidskriftsartikel (refereegranskat)abstract
    • The genetic architecture of human reproductive behavior age at first birth (AFB) and number of children ever born (NEB) has a strong relationship with fitness, human development, infertility and risk of neuropsychiatric disorders. However, very few genetic loci have been identified, and the underlying mechanisms of AFB and NEB are poorly understood. We report a large genome-wide association study of both sexes including 251,151 individuals for AFB and 343,072 individuals for NEB. We identified 12 independent loci that are significantly associated with AFB and/or NEB in a SNP-based genome-wide association study and 4 additional loci associated in a gene-based effort. These loci harbor genes that are likely to have a role, either directly or by affecting non-local gene expression, in human reproduction and infertility, thereby increasing understanding of these complex traits.
  • Brodin, N. Patrik, et al. (författare)
  • Radiobiological risk estimates of adverse events and secondary cancer for proton and photon radiation therapy of pediatric medulloblastoma
  • 2011
  • Ingår i: Acta Oncologica. - Taylor & Francis. - 1651-226X. ; 50:6, s. 806-816
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction. The aim of this model study was to estimate and compare the risk of radiation-induced adverse late effects in pediatric patients with medulloblastoma (MB) treated with either three-dimensional conformal radiotherapy (3D CRT), inversely-optimized arc therapy (RapidArc (R) (RA)) or spot-scanned intensity-modulated proton therapy (IMPT). The aim was also to find dose-volume toxicity parameters relevant to children undergoing RT to be used in the inverse planning of RA and IMPT, and to use in the risk estimations. Material and methods. Treatment plans were created for all three techniques on 10 pediatric patients that have been treated with craniospinal irradiation (CSI) at our institution in 2007-2009. Plans were generated for two prescription CSI doses, 23.4 Gy and 36 Gy. Risk estimates were based on childhood cancer survivor data when available and secondary cancer (SC) risks were estimated as a function of age at exposure and attained age according to the organ-equivalent dose (OED) concept. Results. Estimates of SC risk was higher for the RA plans and differentiable from the estimates for 3D CRT at attained ages above 40 years. The risk of developing heart failure, hearing loss, hypothyroidism and xerostomia was highest for the 3D CRT plans. The risks of all adverse effects were estimated as lowest for the IMPT plans, even when including secondary neutron (SN) irradiation with high values of the neutron radiation weighting factors (WRneutron). Conclusions. When comparing RA and 3D CRT treatment for pediatric MB it is a matter of comparing higher SC risk against higher risks of non-cancer adverse events. Considering time until onset of the different complications is necessary to fully assess patient benefit in such a comparison. The IMPT plans, including SN dose contribution, compared favorably to the photon techniques in terms of all radiobiological risk estimates.
  • Deloukas, Panos, et al. (författare)
  • Large-scale association analysis identifies new risk loci for coronary artery disease
  • 2013
  • Ingår i: Nature Genetics. - Nature Publishing Group. - 1546-1718. ; 45:1, s. 25-33
  • Tidskriftsartikel (refereegranskat)abstract
    • Coronary artery disease (CAD) is the commonest cause of death. Here, we report an association analysis in 63,746 CAD cases and 130,681 controls identifying 15 loci reaching genome-wide significance, taking the number of susceptibility loci for CAD to 46, and a further 104 independent variants (r(2) < 0.2) strongly associated with CAD at a 5% false discovery rate (FDR). Together, these variants explain approximately 10.6% of CAD heritability. Of the 46 genome-wide significant lead SNPs, 12 show a significant association with a lipid trait, and 5 show a significant association with blood pressure, but none is significantly associated with diabetes. Network analysis with 233 candidate genes (loci at 10% FDR) generated 5 interaction networks comprising 85% of these putative genes involved in CAD. The four most significant pathways mapping to these networks are linked to lipid metabolism and inflammation, underscoring the causal role of these activities in the genetic etiology of CAD. Our study provides insights into the genetic basis of CAD and identifies key biological pathways.
  • Eriksson, Olof, et al. (författare)
  • The Positron Emission Tomography ligand [11C]5-Hydroxy-Tryptophan can be used as a surrogate marker for the human endocrine pancreas
  • 2014
  • Ingår i: Diabetes. - 0012-1797 .- 1939-327X. ; 63:10, s. 3428-3437
  • Tidskriftsartikel (refereegranskat)abstract
    • In humans a well-developed serotonin system is localized to the pancreatic islets while being absent in exocrine pancreas. Assessment of pancreatic serotonin biosynthesis could therefore be used to estimate the human endocrine pancreas. Proof of concept was tested in a prospective clinical trial by comparisons of type 1 diabetic (T1D) patients, with extensive reduction of beta cells, with healthy volunteers (HV).C-peptide negative (i.e. insulin-deficient) T1D subjects (n=10) and HV (n=9) underwent dynamic Positron Emission Tomography with the radiolabeled serotonin precursor [(11)C]5-Hydroxy-Tryptophan ([(11)C]5-HTP).A significant accumulation of [(11)C]5-HTP was obtained in the pancreas of the HV, with large inter-individual variation. A substantial and highly significant reduction (66%) in the pancreatic uptake of [(11)C]5-HTP in T1D subjects was observed, and this was most evident in the corpus and caudal regions of the pancreas where beta-cells normally are the major constituent of the islets.[(11)C]5-HTP retention in the pancreas was reduced in T1D compared to non-diabetic subjects. Accumulation of [(11)C]5-HTP in the pancreas of both HV and subjects with T1D were in agreement with previously reported morphological observations on the beta cell volume implying that [(11)C]5-HTP retention is a useful non-invasive surrogate marker for the human endocrine pancreas.
  • Fridh, Magnus, et al. (författare)
  • Hänsynsuppföljning - grunder
  • 2012
  • Rapport (övrigt vetenskapligt)abstract
    • Gruppens f&ouml;rslag I rapporten presenteras de st&auml;llningstaganden och f&ouml;rslag som gruppen hittills kommit fram till, samt bakgrund och motiv f&ouml;r dessa. I rapporten presenteras ocks&aring; n&aring;gra viktiga fr&aring;gor d&auml;r gruppen &auml;nnu inte har n&aring;got f&auml;rdigt f&ouml;rslag. Avsikten &auml;r att rapporten ska underl&auml;tta kommunikationen med &ouml;vriga arbetsgrupper inom Dialog om milj&ouml;h&auml;nsyn och vara en grund f&ouml;r uppf&ouml;ljningsgruppens fortsatta arbete. Syftet med f&ouml;rslagen &auml;r att f&ouml;rb&auml;ttra den uppf&ouml;ljning av milj&ouml;h&auml;nsyn vid avverkning och under f&ouml;ryngringsarbetet som Skogsstyrelsen ansvarar f&ouml;r och f&ouml;r de uppf&ouml;ljningar som skogsbruket g&ouml;r. Gruppen f&ouml;r uppf&ouml;ljning f&ouml;resl&aring;r Skogsstyrelsens ledning att: Uttrycket h&auml;nsynsuppf&ouml;ljning anv&auml;nds ist&auml;llet f&ouml;r Polytax vid myndighetens uppf&ouml;ljning av milj&ouml;h&auml;nsyn vid skogliga &aring;tg&auml;rder. Syftet med uppf&ouml;ljningen &auml;ndras fr&aring;n att utv&auml;rdera tagen milj&ouml;h&auml;nsyn vid f&ouml;ryngringsavverkning genom att relatera den till lagen i taxering till att ge statistik som &auml;r anv&auml;ndbar vid utv&auml;rderingar av de skogspolitiska (milj&ouml;)m&aring;len och milj&ouml;m&aring;len. Uppf&ouml;ljningen ska ocks&aring; vara anv&auml;ndbar i efterf&ouml;ljande l&auml;rande hos mark&auml;garen f&ouml;r att &aring;stadkomma f&ouml;rb&auml;ttrat h&auml;nsynstagande. Begreppet LIT, Lagen I Taxering, utg&aring;r. Uppf&ouml;ljningen ska vara b&auml;ttre faktabaserad &auml;n Polytax. Data som samlas in i f&auml;lt ska i s&aring; stor utstr&auml;ckning som m&ouml;jligt vara m&auml;tbara kvantiteter och i &ouml;vrigt vara bed&ouml;mda kvaliteter med tydliga bed&ouml;mningsgrunder. Utv&auml;rdering g&ouml;rs i huvudsak separat efter uppf&ouml;ljningen, &aring;tskiljd fr&aring;n uppf&ouml;ljningen. Eventuella v&auml;rderande inslag i uppf&ouml;ljningen ska vara l&auml;ttf&ouml;rst&aring;eliga och transparenta och helst g&ouml;ras efter att f&auml;ltdata &auml;r insamlat. F&ouml;reskrifter och allm&auml;nna r&aring;d till 30 &sect; SvL och andra relevanta regelverk anv&auml;nds f&ouml;r att f&aring; konkreta variabler att f&ouml;lja upp men det &auml;r viktigt att uppf&ouml;ljningen h&aring;lls is&auml;r fr&aring;n den r&auml;ttsliga tillsynen. Uppf&ouml;ljningens resultat ska &auml;ven vara anv&auml;ndbara i l&auml;randeprocessen, f&ouml;r att &aring;stadkomma f&ouml;rb&auml;ttrat h&auml;nsynstagande och vid behov ge incitament f&ouml;r att anpassa/ f&ouml;r&auml;ndra regler och rekommendationer. Som en del i att st&auml;rka l&auml;randet b&ouml;r Skogsstyrelsen arbeta fram ett konkret f&ouml;rslag p&aring; hur r&aring;dgivning i &ouml;kad grad kan bygga p&aring; underlag fr&aring;n h&auml;nsynsuppf&ouml;ljningen. Skogsstyrelsen inr&auml;ttar ett externt anv&auml;ndarr&aring;d f&ouml;r uppf&ouml;ljningar inom omr&aring;det skogliga milj&ouml;m&aring;l. St&auml;rka kvalitetss&auml;kringen i uppf&ouml;ljningen genom att kvalitetss&auml;kringen sker efter en fastst&auml;lld metod, integreras med verksamhetsstyrningen i stort och tillf&ouml;rs&auml;kras n&ouml;dv&auml;ndiga resurser. I kvalitetss&auml;kring ing&aring;r att regelbundet genomf&ouml;ra kontrolltaxeringar samt oberoende utv&auml;rderingar gentemot uppf&ouml;ljningens syfte. Statistiken ska ha "tillr&auml;cklig kvalitet" (officiella statistikens begrepp) och uppgift om tillf&ouml;rlitligheten ska f&ouml;lja med resultaten. Personcertifiering av nyckelbiotopskompetens b&ouml;r senare &ouml;verv&auml;gas. Gruppen f&ouml;resl&aring;r skogsbruket att: Ta fram j&auml;mf&ouml;rbara uppf&ouml;ljningssystem som direkt kan nyttjas som underlag tillsammans med Skogsstyrelsens system. Regelbundet f&ouml;lja upp planering av avverkningar och utf&ouml;rda avverkningar. &Ouml;ppet redovisa resultat av uppf&ouml;ljningarna.
  • Hergens, Maria-Pia, et al. (författare)
  • Use of Scandinavian Moist Smokeless Tobacco (Snus) and the Risk of Atrial Fibrillation
  • 2014
  • Ingår i: Epidemiology. - 1044-3983. ; 25:6, s. 872-876
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Snus is a smokeless tobacco product, widely used among Swedish men and increasingly so elsewhere. There is debate as to whether snus is an acceptable "harm-reduction" tobacco product. Since snus use delivers a dose of nicotine equivalent to cigarettes, and has been implicated in cardiac arrhythmia because of associations with sudden cardiovascular death, a relation with atrial fibrillation is plausible and important to investigate.METHODS:: To assess the relation between use of snus and risk of atrial fibrillation, we carried out a pooled analysis of 7 prospective Swedish cohort studies. In total, 274,882 men, recruited between 1978 and 2004, were followed via the National Patient Register for atrial fibrillation. Primary analyses were restricted to 127,907 never-smokers. Relative risks were estimated using Cox proportional hazard regression.RESULTS:: The prevalence of snus use was 25% among never-smokers. During follow-up, 3,069 cases of atrial fibrillation were identified. The pooled relative risk of atrial fibrillation was 1.07 (95% confidence interval = 0.97-1.19) in current snus users, compared with nonusers.CONCLUSION:: Findings from this large national pooling project indicate that snus use is unlikely to confer any important increase in risk of atrial fibrillation.
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