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  • 1.
    Acosta Ruiz, Vanessa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Ladjevardi, Sam
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Brekkan, Einar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Häggman, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Lönnemark, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Wernroth, Lisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Magnusson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Periprocedural outcome after laparoscopic partial nephrectomy versus radiofrequency ablation for T1 renal tumors:: A modified R.E.N.A.L nephrometry score adjusted comparison.2018In: Acta Radiologica, ISSN 0284-1851, E-ISSN 1600-0455, Vol. 60, no 2, p. 260-268Article in journal (Refereed)
    Abstract [en]

    Background: Comparable oncological outcomes have been seen after surgical nephrectomy and thermal ablation of renal tumors recently. However, periprocedural outcome needs to be assessed for aiding treatment decision.

    Purpose: To compare efficacy rates and periprocedural outcome (technical success, session time, hospitalization time, and complications) after renal tumor treatment with laparoscopic partial nephrectomy (LPN) or radiofrequency ablation (RFA).

    Material and Methods: The initial experience with 49 (treated with LPN) and 84 (treated with RFA) consecutive patients for a single renal tumor (diameter ≤ 5 cm, limited to the kidney) during 2007-2014 was evaluated. Patient and tumor characteristics, efficacy rates, and periprocedural outcome were collected retrospectively. The stratified Mantel Haenzel and Van Elteren tests, adjusted for tumor complexity (with the modified R.E.N.A.L nephrometry score [m-RNS]), were used to assess differences in treatment outcomes.

    Results: Primary efficacy rate was 98% for LPN and 85.7% for RFA; secondary efficacy rate was 93.9% for LPN and 95.2% for RFA; and technical success rate was 87.8% for LPN and 100% for RFA. Median session (m-RNS adjusted P < 0.001; LPN 215 min, RFA 137 min) and median hospitalization time were longer after LPN (m-RNS adjusted P < 0.001; LPN 5 days, RFA 2 days). Side effects were uncommon (LPN 2%, RFA 4.8%). Complications were more frequent after LPN (m-RNS adjusted P < 0.001; LPN 42.9%, RFA 10.7%).

    Conclusion: Both methods achieved equivalent secondary efficacy rates. RFA included several treatment sessions, but session and hospitalization times were shorter, and complications were less frequent than for LPN. The differences remained after adjustment for renal tumor complexity.

  • 2.
    Acosta Ruiz, Vanessa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Lönnemark, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Brekkan, Einar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Dahlman, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Wernroth, Lisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Magnusson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Predictive factors for complete renal tumor ablation using RFA2016In: Acta Radiologica, ISSN 0284-1851, E-ISSN 1600-0455, Vol. 57, no 7, p. 886-893Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Radiofrequency ablation (RFA) can be used to treat renal masses in patients where surgery is preferably avoided. As tumor size and location can affect ablation results, procedural planning needs to identify these factors to limit treatment to a single session and increase ablation success.

    PURPOSE: To identify factors that may affect the primary efficacy of complete renal tumor ablation with radiofrequency after a single session.

    MATERIAL AND METHODS: Percutaneous RFA (using an impedance based system) was performed using computed tomography (CT) guidance. Fifty-two renal tumors (in 44 patients) were retrospectively studied (median follow-up, 7 months). Data collection included patient demographics, tumor data (modified Renal Nephrometry Score, histopathological diagnosis), RFA treatment data (electrode placement), and follow-up results (tumor relapse). Data were analyzed through generalized estimating equations.

    RESULTS: Primary efficacy rate was 83%. Predictors for complete ablation were optimal electrode placement (P = 0.002, OR = 16.67) and increasing distance to the collecting system (P = 0.02, OR = 1.18). Tumor size was not a predictor for complete ablation (median size, 24 mm; P = 0.069, OR = 0.47), but all tumors ≤2 cm were completely ablated. All papillary tumors and oncocytomas were completely ablated in a single session; the most common incompletely ablated tumor type was clear cell carcinoma (6 of 9).

    CONCLUSION: Optimal electrode placement and a long distance from the collecting system are associated with an increased primary efficacy of renal tumor RFA. These variables need to be considered to increase primary ablation success. Further studies are needed to evaluate the effect of RFA on histopathologically different renal tumors.

  • 3.
    Byström, Per
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Berglund, Åke
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Nygren, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Wernroth, Lisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Johansson, Birgitta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Evaluation of predictive markers for patients with advanced colorectal cancer2012In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 51, no 7, p. 849-859Article in journal (Refereed)
    Abstract [en]

    Background.

    To evaluate the predictive and prognostic value of serum and plasma tumor markers, in comparison with clinical and biomedical parameters for response rate (RR), progression-free survival (PFS) and overall survival (OS) among patients with metastatic colorectal cancer (mCRC) treated with combination chemotherapy.

    Material and methods.

    One-hundred and six patients with mCRC from three centers, part of a multicenter study, received irinotecan with the Nordic bolus 5-fluorouracil (5-FU) and folinic acid schedule (FLIRI) or the de Gramont schedule (Lv5FU2-IRI). Blood samples for CEA, CA19-9, TPA, TIMP-1, SAA, transthyretin and CRP were taken at baseline and after two, four and eight weeks of treatment. Tumor marker levels at baseline and longitudinally were compared with responses evaluated (CT/MRI) after two and four months of treatment. The correlations to RR, PFS and OS were evaluated with regression analyses.

    Results.

    A significant correlation to OS was seen for baseline levels of all markers. In multivariate analyses with clinical parameters, TPA, CRP, SAA and TIMP-1 provided independent information. The baseline values of CEA, TPA and TIMP-1 were also significantly correlated to PFS and TPA to RR. Changes during treatment, i.e. the slope gave with the exception of CA19-9 for OS less information about outcomes. The best correlation to response was seen for CEA, CA19-9 and TPA with AUC values of 0.78, 0.83 and 0.79, respectively, using a combined model based upon an interaction between the slope and the baseline value.

    Conclusions.

    Baseline tumor markers together with clinical parameters provide prognostic information about survival in patients with mCRC. The ability of the individual tumor markers to predict treatment response and PFS is limited. Changes in marker levels during the first two months of treatment are less informative of outcome.

  • 4.
    Cunningham, Janet L.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Wernroth, Lisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research Center.
    von Knorring, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Berglund, Lars
    Ekselius, Lisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Agreement between physicians' and patients' ratings on the Montgomery-Asberg Depression Rating Scale2011In: Journal of Affective Disorders, ISSN 0165-0327, E-ISSN 1573-2517, Vol. 135, no 1-3, p. 148-153Article in journal (Refereed)
    Abstract [en]

    Background: Self-rating scales developed for monitoring depression severity are potentially informative and cost effective tools. There is an increasing tendency to use the Montgomery-Asberg Depression Rating Scale (MADRS) and the self-rating version (MADRS-S) interchangeably.

    Methods: 400 patients with major depressive disorder were included. Concordance between patient and physician ratings was measured by means of repeated MADRS and MADRS-S ratings during a six-month drug trial and one-year follow-up.

    Results: Overall scores from patients and physicians show the same trends and both are sensitive to improvements. Our results, however, show only moderate to good agreement between patient and physician ratings. Intraclass coefficients ranged from 0.47 to 0.75 with highest agreement at week 8.

    Limitations: Generalizability is restricted to outpatients in general practice with moderate to severe depression. MADRS-S and MADRS scale definitions are similar but not identical concerning language and are scaled differently, 0-6 vs. 0-3, respectively, which may have influenced the results. The exclusion criteria restricted the range of values for the item Suicidal thoughts/Zest for life, which may have reduced the correlations.

    Conclusions: MADRS-S is a suitable tool for following patients' symptoms on a regular basis over time and may also be used to compensate for bias in physicians' ratings in drug trials.

  • 5.
    Cunningham, Janet L.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Wernroth, Lisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    von Knorring, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Berglund, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Ekselius, Lisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Predicting disagreement between physicians and patients on depression response and remission2013In: International Clinical Psychopharmacology, ISSN 0268-1315, E-ISSN 1473-5857, Vol. 28, no 3, p. 134-140Article in journal (Refereed)
    Abstract [en]

    Demographic, personality, and disease-related factors all contribute when patients disagree with physicians on the severity of subjective symptoms. This study aims to create a model, on the basis of patient factors at treatment initiation, for longitudinal prediction of disagreement on treatment response and remission in depressed patients. Four hundred patients with major depressive disorder were studied during a clinical drug trial. Repeated assessments with the Montgomery-Asberg Depression Rating Scale (MADRS) and the self-rating version (MADRS-S) were used to indicate response or remission. Factors at baseline and week 2 were tested for inclusion in a model for the prediction of discordance on remission and response between patients and physicians at week 8. The models were then tested, in the same population, at weeks 12, 16, and 24. Model AUCs ranged from 0.71 to 0.74 for week 8. The models that were validated at weeks 12, 16, and 24 indicated stability in the predictive value of the models. The risk for longitudinal disagreement in the evaluation of depression treatment response and remission in clinical practice and drug trials can be predicted using factors at study initiation and at week 2.

  • 6.
    Helenius, Malin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Dahlman, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Lönnemark, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Brekkan, Einar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Wernroth, Lisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Magnusson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Comparison of post contrast CT urography phases in bladder cancer detection2016In: European Radiology, ISSN 0938-7994, E-ISSN 1432-1084, Vol. 26, no 2, p. 585-591Article in journal (Refereed)
    Abstract [en]

    Objectives The aim of this study was to investigate which post-contrast phase(s) in a four-phase CT urography protocol is (are) most suitable for bladder cancer detection. Methods The medical records of 106 patients with visible haematuria who underwent a CT urography examination, including unenhanced, enhancement-triggered corticomedullary (CMP), nephrographic (NP) and excretory (EP) phases, were reviewed. The post-contrast phases (n = 318 different phases) were randomized into an evaluation order and blindly reviewed by two uroradiologists. Results Twenty-one patients were diagnosed with bladder cancer. Sensitivity for bladder cancer detection was 0.95 in CMP, 0.83 in NP and 0.81 in EP. Negative predictive value (NPV) was 0.99 in CMP, 0.96 in NP and 0.95 in EP. The sensitivity was higher in CMP than in both NP (p-value 0.016) and EP (p-value 0.0003). NPV was higher in CMP than in NP (p-value 0.024) and EP (p-value 0.002). Conclusion In the CT urography protocol with enhancement-triggered scan, sensitivity and NPV were highest in the corticomedullary phase, and this phase should be used for bladder assessment.

  • 7.
    Helgesson, Magnus
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Johansson, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Wernroth, Mona-Lisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Vingård, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Exposure to different lengths of sick leave and subsequent work absence among young adults2016In: BMC Public Health, ISSN 1471-2458, E-ISSN 1471-2458, Vol. 16, article id 51Article in journal (Refereed)
    Abstract [en]

    Background: Sweden has a public and easily accessible sickness insurance. Research shows, however, downsides to taking sick leave. Both short and longer periods of sick leave have been seen to increase the risk for subsequent work absence. The aim of this study was to investigate whether there was an association between sick leave claimed in 1993 and work absence in the subsequent 15 years, i.e. up to 2008. A further aim was to explore differences in this relation with regard to gender, origin and educational level at baseline. Methods: Our cohort consisted of all immigrants aged 21-25 years in Sweden in 1993 and a control group of native Swedes in the same age group. Results: Subsequent work absence increased from 313 days among persons with no days of claimed sick leave in 1993 to 567 days among persons with 1-7 days of claimed sick leave in 1993. Thereafter there was a lower, but steady increase in days of future work absence, to 611 days among persons with 8-14 days of sick leave claimed in 1993. There was an interaction between sick leave and gender, education and origin respectively regarding later work absence. Conclusion: Periods of sick leave claimed were associated with subsequent work absence. Immigrants, women and persons with low education had the most risk of future work absence after a period of sick leave.

  • 8.
    Helgesson, Magnus
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Wernroth, Lisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Vingård, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Length of accumulated sick leave and later work absenceArticle in journal (Other academic)
  • 9.
    Henriksson, Catrin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Larsson, Margareta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Herlitz, Johan
    Karlsson, Jan-Erik
    Wernroth, Lisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Influence of health-related quality of life on time from symptom onset to hospital arrival and the risk of readmission in patients with myocardial infarction2014In: Open heart, E-ISSN 2053-3624, Vol. 1, no 1, p. e000051-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Despite increased awareness of the importance of early treatment in acute myocardial infarction (AMI), the delay from symptom onset to hospital arrival is still too long and rehospitalisations are frequent. Little is known about how health-related quality of life (HRQL) affects delay time and the frequency of readmissions.

    METHOD:

    We used quality registers to investigate whether patients' HRQL has any impact on delay time with a new AMI, and on the rate of readmissions during the first year. Patients with AMI <75 years, with HRQL assessed with EQ-5D at 1-year follow-up, and who thereafter had a new AMI registered, were evaluated for the correlation between HRQL and delay time (n=454). The association between HRQL and readmissions was evaluated among those who had an additional AMI and a new 1-year follow-up registration (n=216).

    RESULTS:

    Patients who reported poor total health status (EQ-VAS ≤50), compared to those who reported EQ-VAS 81-100, had tripled risk to delay ≥2 h from symptom onset to hospital arrival (adjusted OR 3.01, 95% CI 1.43 to 6.34). Patients scoring EQ-VAS ≤50 had also a higher risk of readmissions in the univariate analysis (OR 3.08, 95% CI 1.71 to 5.53). However, the correlation did not remain significant after adjustment (OR 1.99, 95% CI 0.90 to 4.38). EQ-index was not independently associated with delay time or readmissions.

    CONCLUSIONS:

    Aspects of total health status post-AMI were independently associated with delay time to hospital arrival in case of a new AMI. However, the influence of total health status on the risk of readmissions was less clear.

  • 10.
    Henriksson, Catrin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Larsson, Margareta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Judy, Arnetz
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Herlitz, Johan
    Karlsson, Jan-Erik
    Svensson, Leif
    Thuresson, Marie
    Zedig, Crister
    Wernroth, Lisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Knowledge about Acute Myocardial Infarction (AMI) and attitudes to medical care seeking: a comparison between patients and the general public2012In: Open Journal of Nursing, ISSN 2162-5336, E-ISSN 2162-5344, Vol. 2, no 4, p. 372-378Article in journal (Refereed)
    Abstract [en]

    Background:

    Patients with acute myocardial infarction often have long decision times before seeking medical care. The decision time is influenced by knowledge of AMI-symptoms, psychological factors and the response of people near the patient to the symptoms.

    Aim:

    To investigate and compare the knowledge of AMI, intended actions in response to AMI-symptoms and attitudes toward seeking medical care of patients and the general public.

    Method:

    This was a multicentre study with descriptive and comparative design, using questionnaires as an instrument. The population consisted of AMI-patients and representatives of the general public.

    Results:

    There was good knowledge about typical AMI-symptoms among the participants. The majority thought an AMI always starts suddenly. Patients did not know more about the time-dependency of treatment outcome than the general public. A greater proportion of the general public would contact an additional person before consulting medical professionals.

    Conclusions:

    Patients had no better knowledge about AMI than the general public, but would more commonly act appropriately in case of AMI-symptoms.

  • 11.
    Henriksson, Catrin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Wernroth, Lisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Christersson, Christina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science.
    An Observational Study of the Occurence of Anxiety, Depression and self-reported Quality of Life 2 Years after Myocardial Infarction2018In: Journal of Cardiology and Cardiovascular Medicine, ISSN ISSN: 2575-0143, no 3, p. 052-063Article in journal (Refereed)
    Abstract [en]

    Background: Patients with myocardial infarction (MI) often experience anxiety, depression and poor quality of life (QoL) compared with a normative population. Mood disturbances and QoL have been extensively investigated, but only a few studies have examined the long-term effects of MI on these complex phenomena.

    Aims: To examine the levels and associated predictors of anxiety, depression, and QoL in patients 2 years after MI.

    Methods: This was a single center, observational study of patients with MI (n=377, 22% women, median age 66 years). Two years after MI (2012-2014), the patients were asked to answer the Hospital Anxiety and Depression Scale (HADS) and EuroQol 5-dimension (EQ-5D-3L) questionnaires.

    Results: Most patients experienced neither anxiety (87%, 95% confidence interval [CI]: 83-90%) nor depression (94%, 95% CI: 92-97%) 2 years post-MI. Elderly patients experienced more depression than younger patients (p=0.003) and women had higher anxiety levels than men (p=0.009).

    Most patients had “no problems” with any of the EQ-5D-3L dimensions (72-98%), but 48% (95% CI: 43%-53%) self-reported at least “some problems” with pain/discomfort. In a multiple logistic regression model (EQ-5D-3L) higher age (p<0.001) and female sex (p<0.001) were associated with more pain/discomfort. Female sex (p=0.047) and prior MI (p=0.038) were associated with anxiety/depression. History of heart failure was associated with worse mobility (p=0.005) and problems with usual activities (p=0.006). The median total health status of the patients (EQ-VAS) was 78 (95% CI: 75-80)

  • 12.
    Henrohn, Dan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Björkstrand, Kristoffer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Lundberg, Jon O
    Granstam, Sven-Olof
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Baron, Tomasz
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Ingimarsdóttir, Inga J
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Hedenström, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Malinovschi, Andrei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Wernroth, Lisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Jansson, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Hedeland, Mikael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Analytical Science.
    Wikström, Gerhard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Effects of Oral Supplementation With Nitrate-Rich Beetroot Juice in Patients With Pulmonary Arterial Hypertension-Results From BEET-PAH, an Exploratory Randomized, Double-Blind, Placebo-Controlled, Crossover Study.2018In: Journal of Cardiac Failure, ISSN 1071-9164, E-ISSN 1532-8414, Vol. 24, no 10, p. 640-653Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The nitrate-nitrite-nitric oxide (NO) pathway may represent a potential therapeutic target in patients with pulmonary arterial hypertension (PAH). We explored the effects of dietary nitrate supplementation, with the use of nitrate-rich beetroot juice (BRJ), in patients with PAH.

    METHODS AND RESULTS: We prospectively studied 15 patients with PAH in an exploratory randomized, double-blind, placebo-controlled, crossover trial. The patients received nitrate-rich beetroot juice (∼16 mmol nitrate per day) and placebo in 2 treatment periods of 7 days each. The assessments included; exhaled NO and NO flow-independent parameters (alveolar NO and bronchial NO flux), plasma and salivary nitrate and nitrite, biomarkers and metabolites of the NO-system, N-terminal pro-B-type natriuretic peptide, echocardiography, ergospirometry, diffusing capacity of the lung for carbon monoxide, and the 6-minute walk test. Compared with placebo ingestion of BRJ resulted in increases in; fractional exhaled NO at all flow-rates, alveolar NO concentrations and bronchial NO flux, and plasma and salivary levels of nitrate and nitrite. Plasma ornithine levels decreased and indices of relative arginine availability increased after BRJ compared to placebo. A decrease in breathing frequency was observed during ergospirometry after BRJ. A tendency for an improvement in right ventricular function was observed after ingestion of BRJ. In addition a tendency for an increase in the peak power output to peak oxygen consumption ratio (W peak/VO2 peak) was observed, which became significant in patients reaching an increase of plasma nitrite >30% (responders).

    CONCLUSIONS: BRJ administered for 1 week increases pulmonary NO production and the relative arginine bioavailability in patients with PAH, compared with placebo. An increase in the W peak/VO2 peak ratio was observed after BRJ ingestion in plasma nitrite responders. These findings indicate that supplementation with inorganic nitrate increase NO synthase-independent NO production from the nitrate-nitrite-NO pathway.

  • 13.
    Henrohn, Dan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Sandqvist, Anna
    Umea Univ, Umea Univ Hosp, Dept Pharmacol & Clin Neurosci, Umea, Sweden..
    Egerod, Hanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Hedeland, Mikael
    Natl Vet Inst SVA, Dept Chem Environm & Feed Hyg, Uppsala, Sweden.;Uppsala Univ, Div Analyt Pharmaceut Chem, Dept Med Chem, SE-75185 Uppsala, Sweden..
    Wernroth, Lisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Bondesson, Ulf
    Natl Vet Inst SVA, Dept Chem Environm & Feed Hyg, Uppsala, Sweden.;Uppsala Univ, Div Analyt Pharmaceut Chem, Dept Med Chem, SE-75185 Uppsala, Sweden..
    Wikström, Gerhard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Changes in plasma levels of asymmetric dimethylarginine, symmetric dimethylarginine, and arginine after a single dose of vardenafil in patients with pulmonary hypertension2015In: Vascular pharmacology, ISSN 1537-1891, E-ISSN 1879-3649, Vol. 73, p. 71-77Article in journal (Refereed)
    Abstract [en]

    Objective: We investigated whether vardenafil, a phosphodiesterase-5 inhibitor, alters plasma levels of asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), and arginine. Patients and methods: ADMA, SDMA, and arginine were measured (0-540 min) in 12 patients with pulmonary hypertension after a single oral dose of vardenafil. Invasive hemodynamic data were collected at baseline and after 60 min. Results: A reduction in ADMA was observed at 30 and 45 min with a median change of -11.1% (P = 0.021) and -12.5% (P = 0.002). SDMA decreased with a median -5.3% change (P = 0.032) at 45 min. An increase in arginine, median 40.3% (P = 0.002), 45.0% (P = 0.010), and 77.1% (P = 0.008) was observed at 120,300, and 540 min respectively. An increase in the arginine/ADMA ratio, median 11.7% (P = 0.012), 32.5% (P = 0.003), 26.5% (P = 0.021),33% (P = 0.007), 48.5% (P = 0.007), and 63.1% (P = 0.008) was observed at 15, 45, 60, 120, 300, and 540 min respectively. There was a positive correlation between vardenafil exposure and the percent change in the arginine/ADMA ratio from baseline to 540 min (r = 0.80; P = 0.01). A correlation between baseline mean right atrial pressure (mRAP) and baseline ADMA (r = 0.65; P = 0.023), and baseline SDMA (r = 0.61; P = 0.035) was observed. A correlation between the baseline arginine/ADMA ratio and baseline cardiac output (CO) (r = 0.59; P = 0.045) and baseline cardiac index (CI) (r = 0.61; P = 0.036) was observed. Baseline arginine/ADMA ratio correlated with baseline mRAP (r = -0.79; P = 0.002). A correlation between change (0-60 min) in CI and change in arginine (r = 0.77; P = 0.003) as well as change in the arginine/ADMA ratio (r = 0.61; P = 0.037) was observed. Conclusions: Vardenafil induced changes in ADMA, SDMA, arginine, and the arginine/ADMA ratio in patients with PH. An increase in arginine and the arginine/ADMA ratio was associated with improvement in Cl.

  • 14.
    Johansson, Jakob
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Blomberg, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Svennblad, Bodil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Wernroth, Lisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Melhus, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis.
    Byberg, Liisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Karlsten, Rolf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Gedeborg, Rolf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Prehospital Trauma Life Support (PHTLS) training of ambulance caregivers and impact on survival of trauma victims2012In: Resuscitation, ISSN 0300-9572, E-ISSN 1873-1570, Vol. 83, no 10, p. 1259-1264Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    The Prehospital Trauma Life Support (PHTLS) course has been widely implemented and approximately half a million prehospital caregivers in over 50 countries have taken this course. Still, the effect on injury outcome remains to be established. The objective of this study was to investigate the association between PHTLS training of ambulance crew members and the mortality in trauma patients.

    METHODS:

    A population-based observational study of 2830 injured patients, who either died or were hospitalized for more than 24h, was performed during gradual implementation of PHTLS in Uppsala County in Sweden between 1998 and 2004. Prehospital patient records were linked to hospital-discharge records, cause-of-death records, and information on PHTLS training and the educational level of ambulance crews. The main outcome measure was death, on scene or in hospital.

    RESULTS:

    Adjusting for multiple potential confounders, PHTLS training appeared to be associated with a reduction in mortality, but the precision of this estimate was poor (odds ratio, 0.71; 95% confidence interval, 0.42-1.19). The mortality risk was 4.7% (36/763) without PHTLS training and 4.5% (94/2067) with PHTLS training. The predicted absolute risk reduction is estimated to correspond to 0.5 lives saved annually per 100,000 population with PHTLS fully implemented.

    CONCLUSIONS:

    PHTLS training of ambulance crew members may be associated with reduced mortality in trauma patients, but the precision in this estimate was low due to the overall low mortality. While there may be a relative risk reduction, the predicted absolute risk reduction in this population was low.

  • 15.
    Lindqvist, U.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Wernroth, M. L.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Husmark, T.
    Falun Cent Hosp, Dept Rheumatol, Falu, Sweden..
    Larsson, P.
    Karolinska Univ Hosp, Dept Rheumatol, Stockholm, Sweden..
    Geijer, M.
    Lund Univ, Dept Clin Sci, Lund, Sweden.;Univ Hosp, Dept Radiol, Orebro, Sweden..
    Teleman, A.
    Spenshult Hosp, Spenshult AB, Oskarstrom, Sweden..
    Theander, E.
    Lund Univ, Skane Univ Hosp Malmo, Dept Rheumatol, Lund, Sweden..
    Alenius, G. -M
    DAPSA, DAS28 and MDA predict long-term treatment regime in psoriatic arthritis. The Swedish Early Psoriatic Arthritis Cohort2017In: Clinical and Experimental Rheumatology, ISSN 0392-856X, E-ISSN 1593-098X, Vol. 35, no 6, p. 936-942Article in journal (Refereed)
    Abstract [en]

    Objective To describe treatment patterns in the Swedish early psoriatic arthritis cohort (SwePsA) of the mono-/oligo-arthritic (M/O) and polyarthritis (P) and identify early predictive factors for treatment with disease-modifying anti-rheumatic (DMARD), non-steroidal anti-inflammatory drugs (NSAID), and tumour necrosis factor inhibition (TNFi) after 5 years. Methods Data for 198 M/O and P PsA were obtained within the programme for SwePsA. Multinomial and binary logistic regression analyses were used to assess the association between early predictive factors and treatment after 5 years adjusted for age at inclusion. The analysis of DMARD/NSAID was adjusted for medication at inclusion. Results After inclusion visit, DMARD was prescribed in 30% of M/O and 56% of P PsA; mainly methotrexate. TNFi was not prescribed at inclusion, but 23 patients were treated at 5-year follow-up. The adjusted OR (95% CI) for treatment with both DMARD and NSAID after 5 years was 3.65 (1.34 - 9.89) (p=0.010) for Disease Activity Score 28 (DAS28) >3.2 and 2.90 (1.20-6.99) (p=0.038) for Disease Activity Index in Psoriatic Arthritis (DAPSA) >14 at inclusion. TNFi treatment was, after adjusting for age, associated with high erythrocyte sedimentation rate (p=0.0043), high C-reactive protein (p=0.013), DAPSA (p<0.001), not reaching minimal disease activity (p=0.001) high health assessment questionnaire (p=0.001), patient's overall assessment on the visual analogue scale (VAS) (p=0.009), high pain VAS (p=0.007), and high number of tender and swollen joints (p=0.031) at inclusion. Conclusion Disease activity in early M/O and P PsA is to be considered in deciding the level of health care assessment and future pharmacological treatment. DAS28 >3.2 and DAPSA>14 early in the disease predict subsequent treatment with DMARD. For prediction of biological treatment, not reaching MDA at onset of disease, would be the composite index of choice.

  • 16.
    Melkersson, Kristina
    et al.
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden..
    Wernroth, Mona-Lisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Early-onset inguinal hernia as risk factor for schizophrenia or related psychosis: a nationwide register-based cohort study2017In: Neuro - endocrinology letters, ISSN 0172-780X, Vol. 38, no 5, p. 333-342, article id PMID NEL380517A01Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: In an earlier interview study, we found that more men with familial schizophrenia had undergone inguinal hernia operation, than men with sporadic schizophrenia. However, there are no other studies published specifically on inguinal hernia and schizophrenia. Therefore, the aim of this study was to carry out a Swedish register-based cohort study on the association between inguinal hernia and schizophrenia or related psychosis. METHODS: Data from the Total Population-and Medical Birth-Registers were used to create a cohort of all individuals born in Sweden 1987-1999 (n=1 406 168). The cohort individuals were linked with the In-and Out-patient Registers and followed from birth to 2015 to identify onset of schizophrenia, schizoaffective disorder and inguinal hernia. Cox proportional hazards regression models were used to assess the association between inguinal hernia before age 13 and risk of developing schizophrenia or schizoaffective disorder during a follow-up from age 13. RESULTS: Inguinal hernia before age 13 was identified in 21 095 individuals, and during the follow-up in total 1314 individuals developed schizophrenia or schizoaffective disorder. The risk of schizophrenia or schizoaffective disorder was higher among individuals with inguinal hernia before age 13, than among individuals without such a diagnosis, especially among the men [adjusted hazard ratio (95% confidence interval); all: 1.44 (1.01-2.06), p=0.0452, men: 1.46 (1.01-2.12), p=0.0460, women: 0.56 (0.14-2.27), p=0.4173]. CONCLUSIONS: This study shows that early-onset inguinal hernia is associated with increased risk of developing schizophrenia or schizoaffective disorder, especially in men. Such an association may point to a common biological basis for the development of inguinal hernia and schizophrenia or related psychosis.

  • 17.
    Oskarsson, A.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Varenhorst, Christoph
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Hagström, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Wernroth, Mona-Lisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Becker, R. C.
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Himmelmann, A.
    Storey, R. F.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    ApoA1 is independently associated with recurrent ischemic events and death in acute coronary syndrome patients2014In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 35, p. 482-482Article in journal (Refereed)
  • 18.
    Palm, Maria
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Axelsson, Ove
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Wernroth, Lisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation.
    Involvement of inflammation in normal pregnancy2013In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 92, no 5, p. 601-605Article in journal (Refereed)
    Abstract [en]

    Objective.

    To study the role of inflammatory biomarkers of cytokine and cyclooxygenase origin throughout normal pregnancy and postpartum.

    Design.

    Longitudinal prospective study.

    Setting.

    One outpatient antenatal clinic in Uppsala, Sweden.

    Population.

    Thirty-seven healthy women with normal pregnancies and normal neonatal outcome were included. 

    Methods.

    Blood and urine samples were collected from each woman at least 6 times during pregnancy and postpartum. Plasma levels of IL-6 and TNF-α were measured by using ELISA kits and urine levels of PGF2α metabolite were measured by using RIA.

    Main outcome measures.

    Median plasma and urine levels, the 25:th to the 75:th percentile and the average change per gestational week of IL-6, TNF-α and PGF2α metabolite .

    Results.

    IL-6 levels increased significantly throughout pregnancy and postpartum levels remained high. No change in TNF-α could be seen with advancing gestational age or postpartum period. The PGF2α metabolite levels increased significantly throughout pregnancy and decreased in postpartum period.

    Conclusion.

    These results suggest that mild but significant inflammatory activity is involved in development of normal pregnancy and might have important physiological effects.

  • 19.
    Palm, Maria
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Wernroth, Lisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research Center.
    Åkerud, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Axelsson, Ove
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    A longitudinal study of plasma levels of soluble fms-like tyrosine kinase 1 (sFlt1), placental growth factor (PlGF), sFlt1: PlGF ratio and vascular endothelial growth factor (VEGF-A) in normal pregnancy2011In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 90, no 11, p. 1244-1251Article in journal (Refereed)
    Abstract [en]

    Objective: To describe plasma levels of angiogenic (PlGF, VEGF-A) and anti-angiogenic (sFlt1) factors as well as the sFlt1:PlGF ratio throughout normal pregnancy and postpartum.

    Design: Longitudinal prospective study.

    Setting: One outpatient antenatal clinic in Uppsala, Sweden.

    Population: Thirty-seven healthy women with normal pregnancies and normal neonatal outcome were included.

    Methods: Blood samples were collected from each woman at least six times. Plasma levels of sFlt1, PlGF and VEGF-A were measured using commercially available ELISA kits. Main outcome measures. Median plasma levels, the 25th to the 75th percentile and the average change per gestational week of sFlt1, PlGF and the sFlt1:PlGF ratio.

    Results: sFlt1 levels were relatively constant until weeks 29-30, when they increased, reaching a peak at week 40. An increase of 643pg/ml per week was observed from weeks 30 to 40. Postpartum levels were low. PlGF increased by 16pg/ml per week from early pregnancy until weeks 29-30 and thereafter decreased by 14pg/ml per week until week 40. The sFlt1:PlGF ratio decreased from weeks 9-12, was constantly low from weeks 19-20 to 37-38 and then increased to weeks 39-40. VEGF-A was detectable in only 8% of the samples during pregnancy and in 64% postpartum.

    Conclusion: This longitudinal study demonstrates how sFlt1, PlGF and the sFlt1:PlGF ratio fluctuate throughout normal pregnancy and postpartum and may serve as a reference against which these factors can be studied in complicated pregnancies. VEGF-A levels were more often detectable postpartum.

  • 20.
    Sandqvist, Anna
    et al.
    Umea Univ, Div Clin Pharmacol, Dept Pharmacol & Clin Neurosci, Umea, Sweden..
    Henrohn, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Egeröd, Hanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Hedeland, Mikael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Analytical Pharmaceutical Chemistry. Natl Vet Inst SVA, Dept Chem, Uppsala, Sweden..
    Wernroth, Lisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Bondesson, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Analytical Pharmaceutical Chemistry. Natl Vet Inst SVA, Dept Chem, Uppsala, Sweden..
    Schneede, Jorn
    Umea Univ, Div Clin Pharmacol, Dept Pharmacol & Clin Neurosci, Umea, Sweden..
    Wikström, Gerhard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Acute vasodilator response to vardenafil and clinical outcome in patients with pulmonary hypertension2015In: European Journal of Clinical Pharmacology, ISSN 0031-6970, E-ISSN 1432-1041, Vol. 71, no 10, p. 1165-1173Article in journal (Refereed)
    Abstract [en]

    Purpose Acute vasodilator testing is recommended in patients with pulmonary arterial hypertension to identify individuals who may benefit from long-term treatment with oral calcium channel blockers. The aim of this study was to investigate the use of vardenafil in acute vasoreactivity testing compared to adenosine. Methods A total of 20 patients eligible for right heart catheterisation were enrolled. Acute vasoreactivity testing was carried out with intravenous (iv) adenosine (n = 18) followed by oral vardenafil (n = 20). Haemodynamic responses were recorded at baseline and after 60 min (vardenafil). Responders were defined according to consensus guideline criteria. Results Both vardenafil and adenosine significantly decreased mean pulmonary arterial pressure (mPAP, p < 0.001 and p = 0.026, respectively) and pulmonary vascular resistance (p < 0.001 and p > 0.001, respectively), and significantly increased cardiac output (p = 0.001 and p = 0.005, respectively). Vardenafil reduced mPAP more than adenosine (p = 0.044), while adenosine resulted in higher responses of cardiac index (p = 0.009) and pulmonary arterial oxygen saturation (p = 0.042). Acute adverse reactions were common with adenosine, while no side effects were observed after a single oral dose vardenafil. Vardenafil identified five responders (out of 20), while adenosine identified three responders (out of 18). During a 7-year follow-up, vardenafil responders had significantly lower NT-proBNP levels compared to non-responders. Conclusions Vardenafil may be safely used for acute vasoreactivity testing in patients with PH. A single oral dose of vardenafil is better tolerated than iv adenosine and may identify additional responders who could benefit from long-term vasodilator treatment.

  • 21.
    Velders, Matthijs A.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Becker, Richard C.
    van Boven, Adrianus J.
    Himmelmann, Anders
    Husted, Steen
    Katus, Hugo A.
    Lindholm, Daniel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Morais, Joao
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Storey, Robert F.
    Wernroth, Lisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    James, Stefan K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Biomarkers for risk stratification of patients with ST-elevation myocardial infarction treated with primary percutaneous coronary intervention: Insights from the Platelet Inhibition and Patient Outcomes trial2015In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 169, no 6, p. 879-889.e7Article in journal (Refereed)
    Abstract [en]

    Background The incremental prognostic value of admission measurements of biomarkers beyond clinical characteristics and extent of coronary artery disease (CAD) in patients treated with primary percutaneous coronary intervention (PPCI) for ST-elevation myocardial infarction (STEMI) is unclear. Methods Centrally analyzed plasma for biomarker measurements was available in 5,385 of the STEMI patients treated with PPCI in the PLATO trial. Extent of CAD was graded by operators in association with PPCI. We evaluated the prognostic value of high-sensitivity cardiac troponin T, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and growth differentiation factor 15 (GDF-15) beyond clinical characteristics and extent of CAD using Cox proportional hazards analyses, C-index, and net reclassification improvement (NRI). Outcomes were cardiovascular death (CVD) and spontaneous myocardial infarction (MI). Results Angiographic data on extent of CAD improved the prediction of CVD compared to clinical risk factors alone, increasing the C-index from 0.760 to 0.778, total NRI of 0.31. Biomarker information provided additional prognostic value for CVD beyond clinical risk factors and extent of CAD, C-indices ranging from 0.792 to 0.795 for all biomarkers, but with a higher NRI for NT-proBNP. Extent of CAD and high-sensitivity cardiac troponin T were not associated with spontaneous MI. The prediction of spontaneous MI beyond clinical characteristics and extent of CAD (C-index 0.647) was improved by both NT-proBNP (C-index 0.663, NRI 0.22) and GDF-15 (C-index 0.652, NRI 0.05). Conclusions Biomarker measurement on admission is feasible and provides incremental risk stratification in patients with STEMI treated with PPCI, with NT-proBNP and GDF-15 being most valuable due to the association with both CVD and spontaneous MI.

  • 22.
    Wallentin, Lars
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Giannitsis, Evangelos
    Katus, Hugo
    Becker, Richard C.
    Cannon, Christopher P.
    Horrow, Jay
    Husted, Steen
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science.
    Steg, Gabriel P.
    Storey, Robert F.
    Wernroth, Lisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Harrington, Robert
    Outcomes with ticagrelor versus clopidogrel in relation to high sensitivity troponin-T in non-ST-elevation acute coronary syndrome patients managed with early invasive or non-invasive treatment: a substudy from the prospective randomized PLATelet inhibit2013In: Pharmacotherapy, ISSN 0277-0008, E-ISSN 1875-9114, Vol. 33, no 10, p. E189-E189Article in journal (Other academic)
  • 23.
    Wallentin, Lars
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Lindholm, Daniel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Wernroth, Lisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Becker, Richard C.
    Cannon, Christopher P.
    Cornel, Jan H.
    Himmelmann, Anders
    Giannitsis, Evangelos
    Harrington, Robert A.
    Held, Claes
    Husted, Steen
    Katus, Hugo A.
    Mahaffey, Kenneth W.
    Steg, Ph. Gabriel
    Storey, Robert F.
    James, Stefan K.
    Biomarkers in Relation to the Effects of Ticagrelor in Comparison With Clopidogrel in Non-ST-Elevation Acute Coronary Syndrome Patients Managed With or Without In-Hospital Revascularization A Substudy From the Prospective Randomized Platelet Inhibition and Patient Outcomes (PLATO) Trial2014In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 129, no 3, p. 293-303Article in journal (Refereed)
    Abstract [en]

    Background Risk stratification and the use of specific biomarkers have been proposed for tailoring treatment in patients with non-ST-elevation acute coronary syndrome (NSTE-ACS). We investigated the prognostic importance of high-sensitivity troponin T (hs-TnT), N-terminal pro-brain natriuretic peptide (NT-proBNP), and growth differentiation factor-15 (GDF-15) in relation to randomized treatment (ticagrelor versus clopidogrel) and management strategy (with or without revascularization) in the NSTE-ACS subgroup of the Platelet Inhibition and Patient Outcomes (PLATO) trial. Methods and Results Of 18 624 patients in the PLATO trial, 9946 had an entry diagnosis of NSTE-ACS and baseline blood samples available. During index hospitalization, 5357 were revascularized, and 4589 were managed without revascularization. Hs-TnT, NT-proBNP, and GDF-15 were determined and assessed according to predefined cutoff levels. Median follow-up was 9.1 months. Increasing levels of hs-TnT were associated with increasing risk of cardiovascular death, myocardial infarction, and stroke in medically managed patients (P<0.001), but not in those managed invasively. NT-proBNP and GDF-15 levels were associated with the same events independent of management strategy. Ticagrelor versus clopidogrel reduced the rate of cardiovascular death, myocardial infarction, and stroke in patients with NSTE-ACS and hs-TnT 14.0 ng/L in both invasively and noninvasively managed patients; in patients with hs-TnT <14.0 ng/L, there was no difference between ticagrelor and clopidogrel in the noninvasive group Conclusions Hs-TnT, NT-proBNP, and GDF-15 are predictors of cardiovascular death, myocardial infarction, and stroke in patients with NSTE-ACS managed noninvasively, and NT-proBNP and GDF-15 also in those managed invasively. Elevated hs-TnT predicts substantial benefit of ticagrelor over clopidogrel both in invasively and noninvasively managed patients, but no apparent benefit was seen at normal hs-TnT. Clinical Trial Registration URL:http://www.clinicaltrials.gov. Unique identifier: NCT00391872.

  • 24.
    Wernroth, Mona-Lisa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Svennblad, Bodil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Fall, Katja
    Orebro Univ, Sch Med Sci, Clin Epidemiol & Biostat, Orebro, Sweden..
    Fang, Fang
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden..
    Almqvist, Catarina
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.;Karolinska Univ Hosp, Astrid Lindgren Childrens Hosp, Lung & Allergy Unit, Stockholm, Sweden..
    Fall, Tove
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Dog Exposure During the First Year of Life and Type 1 Diabetes in Childhood2017In: JAMA pediatrics, ISSN 2168-6203, E-ISSN 2168-6211, Vol. 171, no 7, p. 663-669Article in journal (Refereed)
    Abstract [en]

    IMPORTANCE The association between early exposure to animals and type 1 diabetes in childhood is not clear. OBJECTIVE To determine whether exposure to dogs during the first year of life is associated with the development of type 1 diabetes in childhood. DESIGN, SETTING, AND PARTICIPANTS A nationwide cohort study utilizing high-quality Swedish national demographic and health registers was conducted. A total of 840 593 children born in Sweden from January 1, 2001, to December 31, 2010, were evaluated. Type 1 diabetes was identified using diagnosis codes from hospitals and dispensed prescriptions of insulin. Cox proportional hazards regression models were used to assess the association between exposure to dogs and risk of type 1 diabetes in childhood. The possible association was further investigated by performing dose-response and breed group-specific analyses. The cohort was followed up until September 30, 2012. Data analysis was conducted from October 15, 2015, to February 8, 2017. EXPOSURES Having a parent who was registered as a dog owner during the child's first year of life. MAIN OUTCOMES AND MEASURES Childhood-onset type 1 diabetes. RESULTS Of the 840 593 children reviewed, 408 272 (48.6%) were girls; mean (SD) age at diagnosis of type 1 diabetes was 5.1 (2.6) years. Dog exposure was identified in 102 035 children (12.1%). Follow-up started at age 1 year, and the children were followed up for as long as 10.7 years (median, 5.5 years). During follow-up, 1999 children developed type 1 diabetes. No association was found between exposure to dogs (adjusted hazard ratio [HR], 1.00; 95% CI, 0.86-1.16) and type 1 diabetes in childhood. The size of the dog (adjusted HR per 10-cm increase in height, 0.96; 95% CI, 0.86-1.06) or number of dogs in the household (1 dog: adjusted HR, 1.07; 95% CI, 0.91-1.26; 2 dogs: 0.79; 95% CI, 0.54-1.15; >= 3 dogs: 0.50; 95% CI, 0.23-1.12; compared with nonexposed children) also was not associated with type 1 diabetes risk. An analysis of children whose parent had type 1 diabetes (210 events) yielded an adjusted HR of 0.71 (95% CI, 0.43-1.17) for dog exposure. CONCLUSIONS AND RELEVANCE In a nationwide study, no evidence supporting an association of register-derived measures of dog exposure with childhood type 1 diabetes was identified.

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