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  • Rystedt, Jenny M. L., et al. (författare)
  • Post cholecystectomy bile duct injury : early, intermediate or late repair with hepaticojejunostomy - an E-AHPBA multi-center study
  • 2019
  • Ingår i: HPB. - : Elsevier. - 1365-182X .- 1477-2574. ; 21:12, s. 1641-1647
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Treatment of bile duct injuries (BDI) during cholecystectomy depends on the severity of injury and the timing of diagnosis. Standard of care for severe BDIs is hepaticojejunostomy. The aim of this retrospective multi-center study was to assess the optimal timing for repair of BDI with hepaticojejunostomy.Methods: Members of the European-African HepatoPancreatoBiliary Association were invited to report all consecutive patients with hepaticojejunostomy after BDI from January 2000 to June 2016. Patients were stratified according to the timing of biliary reconstruction with hepaticojejunostomy: early (day 0-7), intermediate (1-6 weeks) and late (6 weeks-6 months). Primary endpoint was re-intervention >90 days after the hepaticojejunostomy and secondary endpoints were severe 90-day complications and liver-related mortality.Results: In total 913 patients from 48 centers were included in the analysis. In 401 patients (44%) the bile duct injury was diagnosed intraoperatively, and 126 patients (14%) suffered from concomitant vascular injury. In multivariable analysis the timing of hepaticojejunostomy had no impact on postoperative complications, the need for re-intervention after 90 days nor liver-related mortality. The rate of re-intervention more than 90 days after the hepaticojejunostomy was significantly increased in male patients but decreased in older patients. Severe co-morbidity increased the risk for liver-related mortality (HR 3.439; CI 1.37-8.65; p = 0.009).Conclusion: After BDI occurring during cholecystectomy, the timing of biliary reconstruction with hepaticojejunostomy did not have any impact on severe postoperative complications, the need for re-intervention or liver-related mortality. Individualised treatment after iatrogenic bile duct injury is still advisable.
  • Fu, M., et al. (författare)
  • Adherence to optimal heart rate control in heart failure with reduced ejection fraction : insight from a survey of heart rate in heart failure in Sweden (HR-HF study)
  • 2017
  • Ingår i: Clinical Research in Cardiology. - : SPRINGER HEIDELBERG. - 1861-0684 .- 1861-0692. ; 106:12, s. 960-973
  • Tidskriftsartikel (refereegranskat)abstract
    • Despite that heart rate (HR) control is one of the guideline-recommended treatment goals for heart failure (HF) patients, implementation has been painstakingly slow. Therefore, it would be important to identify patients who have not yet achieved their target heart rates and assess possible underlying reasons as to why the target rates are not met. The survey of HR in patients with HF in Sweden (HR-HF survey) is an investigator-initiated, prospective, multicenter, observational longitudinal study designed to investigate the state of the art in the control of HR in HF and to explore potential underlying mechanisms for suboptimal HR control with focus on awareness of and adherence to guidelines for HR control among physicians who focus on the contributing role of beta-blockers (BBs). In 734 HF patients the mean HR was 68 +/- 12 beats per minute (bpm) (37.2% of the patients had a HR > 70 bpm). Patients with HF with reduced ejection fraction (HFrEF) (n = 425) had the highest HR (70 +/- 13 bpm, with 42% > 70 bpm), followed by HF with preserved ejection fraction and HF with mid-range ejection fraction. Atrial fibrillation, irrespective of HF type, had higher HR than sinus rhythm. A similar pattern was observed with BB treatment. Moreover, non-achievement of the recommended target HR (< 70 bpm) in HFrEF and sinus rhythm was unrelated to age, sex, cardiovascular risk factors, cardiovascular diseases, and comorbidities, but was related to EF and the clinical decision of the physician. Approximately 50% of the physicians considered a HR of > 70 bpm optimal and an equal number considered a HR of > 70 bpm too high, but without recommending further action. Furthermore, suboptimal HR control cannot be attributed to the use of BBs because there was neither a difference in use of BBs nor an interaction with BBs for HR > 70 bpm compared with HR < 70 bpm. Suboptimal control of HR was noted in HFrEF with sinus rhythm, which appeared to be attributable to physician decision making rather than to the use of BBs. Therefore, our results underline the need for greater attention to HR control in patients with HFrEF and sinus rhythm and thus a potential for improved HF care.
  • Månsson, K. N. T., et al. (författare)
  • Neuroplasticity in response to cognitive behavior therapy for social anxiety disorder
  • 2016
  • Ingår i: Translational Psychiatry. - : NATURE PUBLISHING GROUP. - 2158-3188 .- 2158-3188. ; 6
  • Tidskriftsartikel (refereegranskat)abstract
    • Patients with anxiety disorders exhibit excessive neural reactivity in the amygdala, which can be normalized by effective treatment like cognitive behavior therapy (CBT). Mechanisms underlying the brain’s adaptation to anxiolytic treatments are likely related both to structural plasticity and functional response alterations, but multimodal neuroimaging studies addressing structure–function interactions are currently missing. Here, we examined treatment-related changes in brain structure (gray matter (GM) volume) and function (blood–oxygen level dependent, BOLD response to self-referential criticism) in 26 participants with social anxiety disorder randomly assigned either to CBT or an attention bias modification control treatment. Also, 26 matched healthy controls were included. Significant time × treatment interactions were found in the amygdala with decreases both in GM volume (family-wise error (FWE) corrected PFWE=0.02) and BOLD responsivity (PFWE=0.01) after successful CBT. Before treatment, amygdala GM volume correlated positively with anticipatory speech anxiety (PFWE=0.04), and CBT-induced reduction of amygdala GM volume (pre–post) correlated positively with reduced anticipatory anxiety after treatment (PFWE0.05). In addition, we observed greater amygdala neural responsivity to self-referential criticism in socially anxious participants, as compared with controls (PFWE=0.029), before but not after CBT. Further analysis indicated that diminished amygdala GM volume mediated the relationship between decreased neural responsivity and reduced social anxiety after treatment (P=0.007). Thus, our results suggest that improvement-related structural plasticity impacts neural responsiveness within the amygdala, which could be essential for achieving anxiety reduction with CBT.
  • Hugosson, Jonas, 1955, et al. (författare)
  • A 16-yr Follow-up of the European Randomized study of Screening for Prostate Cancer
  • 2019
  • Ingår i: European Urology. - : Elsevier. - 0302-2838. ; 76:1, s. 43-51
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The European Randomized study of Screening for Prostate Cancer (ERSPC) has previously demonstrated that prostate-specific antigen (PSA) screening decreases prostate cancer (PCa) mortality. Objective: To determine whether PSA screening decreases PCa mortality for up to 16 yr and to assess results following adjustment for nonparticipation and the number of screening rounds attended. Design, setting, and participants: This multicentre population-based randomised screening trial was conducted in eight European countries. Report includes 182 160 men, followed up until 2014 (maximum of 16 yr), with a predefined core age group of 162 389 men (55-69 yr), selected from population registry. Outcome measurements and statistical analysis: The outcome was PCa mortality, also assessed with adjustment for nonparticipation and the number of screening rounds attended. Results and limitations: The rate ratio of PCa mortality was 0.80 (95% confidence interval [CI] 0.72-0.89, p < 0.001) at 16 yr. The difference in absolute PCa mortality increased from 0.14% at 13 yr to 0.18% at 16 yr. The number of men needed to be invited for screening to prevent one PCa death was 570 at 16 yr compared with 742 at 13 yr. The number needed to diagnose was reduced to 18 from 26 at 13 yr. Men with PCa detected during the first round had a higher prevalence of PSA >20 ng/ml (9.9% compared with 4.1% in the second round, p < 0.001) and higher PCa mortality (hazard ratio = 1.86, p < 0.001) than those detected subsequently. Conclusions: Findings corroborate earlier results that PSA screening significantly reduces PCa mortality, showing larger absolute benefit with longer follow-up and a reduction in excess incidence. Repeated screening may be important to reduce PCa mortality on a population level. Patient summary: In this report, we looked at the outcomes from prostate cancer in a large European population. We found that repeated screening reduces the risk of dying from prostate cancer. (C) 2019 Published by Elsevier B.V. on behalf of European Association of Urology.
  • Månsson, K. N. T., et al. (författare)
  • Predicting long-term outcome of Internet-delivered cognitive behavior therapy for social anxiety disorder using fMRI and support vector machine learning
  • 2015
  • Ingår i: Translational Psychiatry. - 2158-3188 .- 2158-3188. ; 5
  • Tidskriftsartikel (refereegranskat)abstract
    • Cognitive behavior therapy (CBT) is an effective treatment for social anxiety disorder (SAD), but many patients do not respond sufficiently and a substantial proportion relapse after treatment has ended. Predicting an individual’s long-term clinical response therefore remains an important challenge. This study aimed at assessing neural predictors of long-term treatment outcome in participants with SAD 1 year after completion of Internet-delivered CBT (iCBT). Twenty-six participants diagnosed with SAD underwent iCBT including attention bias modification for a total of 13 weeks. Support vector machines (SVMs), a supervised pattern recognition method allowing predictions at the individual level, were trained to separate long-term treatment responders from nonresponders based on blood oxygen level-dependent (BOLD) responses to self-referential criticism. The Clinical Global Impression-Improvement scale was the main instrument to determine treatment response at the 1-year follow-up. Results showed that the proportion of long-term responders was 52%(12/23). From multivariate BOLD responses in the dorsal anterior cingulate cortex (dACC) together with the amygdala, we were able to predict long-term response rate of iCBT with an accuracy of 92% (confidence interval 95% 73.2–97.6). This activation pattern was, however, not predictive of improvement in the continuous Liebowitz Social Anxiety Scale—Self-report version. Follow-up psychophysiological interaction analyses revealed that lower dACC–amygdala coupling was associated with better long-term treatment response. Thus, BOLD response patterns in the fear-expressing dACC–amygdala regions were highly predictive of long-term treatment outcome of iCBT, and the initial coupling between these regions differentiated long-term responders from nonresponders. The SVM-neuroimaging approach could be of particular clinical value as it allows for accurate prediction of treatment outcome at the level of the individual.
  • Dahl, M., et al. (författare)
  • Lentiviral Gene Therapy Using Cellular Promoters Cures Type 1 Gaucher Disease in Mice
  • 2015
  • Ingår i: Molecular Therapy. - : Nature Publishing Group. - 1525-0016 .- 1525-0024. ; 23:5, s. 835-844
  • Tidskriftsartikel (refereegranskat)abstract
    • Gaucher disease is caused by an inherited deficiency of the enzyme glucosylceramidase. Due to the lack of a fully functional enzyme, there is progressive build-up of the lipid component glucosylceramide. Insufficient glucosylceramidase activity results in hepatosplenomegaly, cytopenias, and bone disease in patients. Gene therapy represents a future therapeutic option for patients unresponsive to enzyme replacement therapy and lacking a suitable bone marrow donor. By proof-of-principle experiments, we have previously demonstrated a reversal of symptoms in a murine disease model of type 1 Gaucher disease, using gammaretroviral vectors harboring strong viral promoters to drive glucosidase beta-acid (GBA) gene expression. To investigate whether safer vectors can correct the enzyme deficiency, we utilized self-inactivating lentiviral vectors (SIN LVs) with the GBA gene under the control of human phosphoglycerate kinase (PGK) and CD68 promoter, respectively. Here, we report prevention of, as well as reversal of, manifest disease symptoms after lentiviral gene transfer. Glucosylceramidase activity above levels required for clearance of glucosylceramide from tissues resulted in reversal of splenomegaly, reduced Gaucher cell infiltration and a restoration of hematological parameters. These findings support the use of SIN-LVs with cellular promoters in future clinical gene therapy protocols for type 1 Gaucher disease.
  • Shev, S, et al. (författare)
  • HCV genotypes in Swedish blood donors as correlated to epidemiology, liver disease and hepatitis C virus antibody profile
  • 1995
  • Ingår i: Infection. - : Urban & Vogel. - 1439-0973 .- 0300-8126. ; 23:5, s. 253-257
  • Tidskriftsartikel (refereegranskat)abstract
    • Sixty-two anti-HCV and HCV-RNA positive Swedish blood donors (44 men, 18 women; median age 34 years) were studied. HCV genotypes were correlated to parenteral risk factors, liver morphology, serum alanine aminotransferase (ALAT) levels and HCV antibody profile. Forty percent of the donors were infected with HCV genotype 1a, 10% with 1b, 21% with 2b, and 29% with 3a. Intravenous drug use (IVDU) was more common in donors with genotype 3a than in those with genotype 1a (p = 0.024), and prior blood transfusion more common in genotype 2b than in 3a (p = 0.012). Chronic active hepatitis with and without cirrhosis was found in 38% of donors infected with genotype 2b as compared to 8% of donors infected with 1a (p = 0.034). Forty percent of donors with genotype 1a had normal ALAT at the time of liver biopsy versus 11% with genotype 3a (p = 0.046). Antibodies to C33c and C22-3 were present in nearly all donors whereas reactivity to C100-3 and 5-1-1 was detected more often in donors with genotypes 1a and 1b as compared to donors with genotypes 2b and 3a. In conclusion, genotype 3a was correlated to IVDU or tattooing as parenteral risk factors for the acquisition of HCV infection, and genotype 2b to prior blood transfusion. Donors with genotypes 1a seemed to have less severe liver disease than those infected with genotypes 2b and 3a.
  • Svalkvist, Angelica, et al. (författare)
  • Evaluation of an improved method of simulating lung nodules in chest tomosynthesis.
  • 2012
  • Ingår i: Acta radiologica. - : Informa Healthcare / Wiley-Blackwell / Royal Society of Medicine Press. - 1600-0455 .- 0284-1851. ; 53:8, s. 874-884
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundSimulated pathology is a valuable complement to clinical images in studies aiming at evaluating an imaging technique. In order for a study using simulated pathology to be valid, it is important that the simulated pathology in a realistic way reflect the characteristics of real pathology.PurposeTo perform a thorough evaluation of a nodule simulation method for chest tomosynthesis, comparing the detection rate and appearance of the artificial nodules with those of real nodules in an observer performance experiment.Material and MethodsA cohort consisting of 64 patients, 38 patients with a total of 129 identified pulmonary nodules and 26 patients without identified pulmonary nodules, was used in the study. Simulated nodules, matching the real clinically found pulmonary nodules by size, attenuation, and location, were created and randomly inserted into the tomosynthesis section images of the patients. Three thoracic radiologists and one radiology resident reviewed the images in an observer performance study divided into two parts. The first part included nodule detection and the second part included rating of the visual appearance of the nodules. The results were evaluated using a modified receiver-operating characteristic (ROC) analysis.ResultsThe sensitivities for real and simulated nodules were comparable, as the area under the modified ROC curve (AUC) was close to 0.5 for all observers (range, 0.43-0.55). Even though the ratings of visual appearance for real and simulated nodules overlapped considerably, the statistical analysis revealed that the observers to were able to separate simulated nodules from real nodules (AUC values range 0.70-0.74).ConclusionThe simulation method can be used to create artificial lung nodules that have similar detectability as real nodules in chest tomosynthesis, although experienced thoracic radiologists may be able to distinguish them from real nodules.
  • Tingberg, A, et al. (författare)
  • Influence of the characteristic curve on the clinical image quality of lumbar spine and chest radiographs.
  • 2004
  • Ingår i: The British journal of radiology. - : British Inst Radiology. - 0007-1285 .- 1748-880X. ; 77:915, s. 204-15
  • Tidskriftsartikel (refereegranskat)abstract
    • The "European Guidelines on Quality Criteria for Diagnostic Radiographic Images" do not address the choice of the film characteristic (H&D) curve, which is an important parameter for the description of a radiographic screen-film system. The image contrast of clinical lumbar spine and chest radiographs was altered by digital image processing techniques, simulating images with different H&D curves, both steeper and flatter than the original. The manipulated images were printed on film for evaluation. Seven experienced radiologists evaluated the clinical image quality by analysing the fulfilment of the European Image Criteria (ICS) and by visual grading analysis (VGA) of in total 224 lumbar spine and 360 chest images. A parallel study of the effect of the H&D curve has also been made using a theoretical model. The contrast (DeltaOD) of relevant anatomical details was calculated, using a Monte Carlo simulation-model of the complete imaging system including a 3D voxel phantom of a patient. Correlations between the calculated contrast and the radiologists' assessment by VGA were sought. The results of the radiologists' assessment show that the quality in selected regions of lumbar spine and chest images can be significantly improved by the use of films with a steeper H&D curve compared with the standard latitude film. Significant (p<0.05) correlations were found between the VGA results and the calculations of the contrast of transverse processes and trabecular details in the lumbar spine vertebrae, and with the contrast of blood vessels in the retrocardiac area of the chest.
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