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  • 51.
    Graipe, Anna
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Söderström, Lars
    Mooe, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Increased Use of Ticagrelor After Myocardial Infarction Is Not Associated With Intracranial Hemorrhage: Results From a Nationwide Swedish Registry2018Ingår i: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 49, nr 12, s. 2877-2882Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background and Purpose: Guidelines recommend dual antiplatelet treatment with ticagrelor instead of clopidogrel after acute myocardial infarction. Ticagrelor increases major and minor noncoronary artery bypass graft bleeding compared with clopidogrel, but whether the risk of intracranial hemorrhage (ICH) increases is unknown. We aimed to examine any association between ticagrelor and ICH and to identify predictors of ICH among unselected patients after acute myocardial infarction.

    Methods: Patients with acute myocardial infarction were identified using the Register of Information and Knowledge About Swedish Heart Intensive Care Admissions, and the data were combined with the Swedish National Patient Registry to identify ICH occurrence. To avoid obvious selection bias related to the choice of dual antiplatelet treatment, we divided the study cohorts into 2 time periods of similar length using the first prescription of ticagrelor as a cutoff point (December 20, 2011). The risk of ICH during the first period (100% clopidogrel treatment) versus the second period (52.1% ticagrelor and 47.8% clopidogrel treatment) was assessed using Kaplan-Meier analysis. Cox proportional-hazards regression analyses, with assessment of interactions between all significant variables, were used to identify predictors of ICH.

    Results: The analysis included 47 674 patients with acute myocardial infarction. The cumulative incidence of ICH during the first period was 0.59% (91 cases [95% CI, 0.49-0.69]) versus 0.52% (97 cases [95% CI, 0.43-0.61]) during the second period (P=0.83). In multivariable Cox analysis, study period (second versus first period) was not predictive of ICH. Interaction analyses showed that age and prior cardiovascular morbidities were of importance in predicting the risk of ICH.

    Conclusions: The increased use of ticagrelor was not associated with ICH, whereas age and prior cardiovascular morbidities were related to the risk of ICH and interacted significantly.

  • 52.
    Gunnarsson, Niklas
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Hoglund, M.
    Stenke, L.
    Sandin, F.
    Bjorkholm, M.
    Dreimane, A.
    Lambe, M.
    Markevarn, B.
    Olsson-Stromberg, U.
    Wadenvik, H.
    Richter, J.
    Sjalander, A.
    No increased prevalence of malignancies among first-degree relatives of 800 patients with chronic myeloid leukemia: a population-based study in Sweden2017Ingår i: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 31, nr 8, s. 1825-1827Artikel i tidskrift (Refereegranskat)
  • 53.
    Gustafsson, Nils
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Ahlqvist, Jan B.
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Näslund, Ulf
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Wester, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin. Department of Clinical Sciences, Karolinska Institutet Danderyds Hospital, Stockholm, Sweden..
    Buhlin, Kare
    Gustafsson, Anders
    Levring Jäghagen, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Calcified carotid artery atheromas in panoramic radiographs are associated with a first myocardial infarction: a case-control study2018Ingår i: Oral surgery, oral medicine, oral pathology and oral radiology, ISSN 2212-4403, E-ISSN 2212-4411, Vol. 125, nr 2, s. 199-205Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective. The aim of this case-control study was to investigate whether patients with a first myocardial infarction (MI) had a higher prevalence of calcified carotid artery atheromas (CCAAs) on panoramic radiographs (PRs) than age-, gender-, and residential area-matched controls without MI. Study Design. Six hundred ninety-six cases with a first MI and 696 controls were included in this substudy of the Swedish multicentre PAROKRANK study. All participants underwent panoramic radiography, and the PRs were evaluated for CCAAs. Results. The prevalence of CCAAs detected by PR was 33.8% (235 of 696) in cases and 27.6% (192 of 696) in controls (odds ratio [OR] 1.24; 95% confidence interval [CI] 1.04-1.44; P = .012). Among males, 32.7% of cases (184 of 562) and 26.5% of controls (149 of 562) displayed CCAAs on PRs (OR 1.24; 95% CI 1.03-1.48; P = .022). Among both genders, bilateral CCAAs were significantly more common among cases than among controls (P = .002). Conclusions. Cases with recent MIs had a significantly higher prevalence of CCAAs on PRs compared with controls without MIs. This difference between groups was more pronounced for bilateral CCAAs. These findings supported the hypothesis that CCAA detection could serve as a risk indicator for future MIs.

  • 54.
    Gylfe, Åsa
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk bakteriologi.
    Ribers, Åsa
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Forsman, Oscar
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Bucht, Göran
    Alenius, Gerd-Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Wållberg-Jonsson, Solveig
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Ahlm, Clas
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Evander, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Mosquitoborne Sindbis Virus Infection and Long-Term Illness2018Ingår i: Emerging Infectious Diseases, ISSN 1080-6040, E-ISSN 1080-6059, Vol. 24, nr 6, s. 1141-1142Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    An unexpected human outbreak of the mosquitoborne Sindbis virus occurred in a previously nonendemic area of Sweden. At follow-up, 6-8 months after infection, 39% of patients had chronic arthralgia that affected their daily activities. Vectorborne infections may disseminate rapidly into new areas and cause acute and chronic disease.

  • 55. Hallén, Magnus
    et al.
    Sevonius, Dan
    Holmberg, Henrik
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Sandblom, Gabriel
    Low complication rate and an increasing incidence of surgical repair of primary indirect sliding inguinal hernia2016Ingår i: Langenbeck's archives of surgery (Print), ISSN 1435-2443, E-ISSN 1435-2451, Vol. 401, nr 2, s. 215-222Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose The purpose of the present study was to explore the risk for complications and reoperations following open repairs for sliding groin hernias.

    Method All primary indirect inguinal hernia repairs registered in the Swedish Hernia Register 1998–2011 were identified. Repeated and bilateral procedures were excluded. The epidemiology, the incidence of per- and postoperative complications, and the reoperation rate due to recurrences were analyzed.

    Results 100 240 non-repeated unilateral repairs were registered with sliding hernias in 13 132 (13.1 %) (male 14 %, female 5 %) procedures. The methods of repair for sliding and non-sliding hernias were Lichtenstein and other open anterior mesh repairs (N = 10865, 82.7 % and N = 60790, 69.8 %), endoscopic techniques (N = 136, 1.0 % and N= 4352, 5.0 %), and other techniques (N= 2131, 16.2 % and N= 21966, 25.2 %). In multivariate analyses with adjustment for gender, acute/planned surgery, reducibility, method of repair and age, sliding hernias were associated with a low but slightly increased risk for perioperative complications (hazard ratio 1.30, 95 % confidence interval 1.04–1.62, p = 0.023) and postoperative hematoma (hazard ratio 1.13, confidence interval 1.02–1.26, p =0.019). There was no increased risk of reoperation due to recurrences.

    Conclusion Compared to older reports, the incidence of repairs due to primary indirect sliding inguinal hernias has increased over time and it is not just a male disease. The overall results are good with low and comparable complication rates, and no increased risk of reoperations due to recurrences.

  • 56. Haworth, Simon
    et al.
    Shungin, Dmitry
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi. Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA.
    van der Tas, Justin T
    Vucic, Strahinja
    Medina-Gomez, Carolina
    Yakimov, Victor
    Feenstra, Bjarke
    Shaffer, John R
    Lee, Myoung Keun
    Standl, Marie
    Thiering, Elisabeth
    Wang, Carol
    Bønnelykke, Klaus
    Waage, Johannes
    Jessen, Leon Eyrich
    Nørrisgaard, Pia Elisabeth
    Joro, Raimo
    Seppälä, Ilkka
    Raitakari, Olli
    Dudding, Tom
    Grgic, Olja
    Ongkosuwito, Edwin
    Vierola, Anu
    Eloranta, Aino-Maija
    West, Nicola X
    Thomas, Steven J
    McNeil, Daniel W
    Levy, Steven M
    Slayton, Rebecca
    Nohr, Ellen A
    Lehtimäki, Terho
    Lakka, Timo
    Bisgaard, Hans
    Pennell, Craig
    Kühnisch, Jan
    Marazita, Mary L
    Melbye, Mads
    Geller, Frank
    Rivadeneira, Fernando
    Wolvius, Eppo B
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin. Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Malmö 202 13, Sweden; Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA.
    Johansson, Ingegerd
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Timpson, Nicholas J
    Consortium-based genome-wide meta-analysis for childhood dental caries traits2018Ingår i: Human Molecular Genetics, ISSN 0964-6906, E-ISSN 1460-2083, Vol. 27, nr 17, s. 3113-3127Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Prior studies suggest dental caries traits in children and adolescents are partially heritable, but there has been no large-scale consortium genome-wide association study (GWAS) to date. We therefore performed GWAS for caries in participants aged 2.5-18.0 years from nine contributing centres. Phenotype definitions were created for the presence or absence of treated or untreated caries, stratified by primary and permanent dentition. All studies tested for association between caries and genotype dosage and the results were combined using fixed-effects meta-analysis. Analysis included up to 19 003 individuals (7530 affected) for primary teeth and 13 353 individuals (5875 affected) for permanent teeth. Evidence for association with caries status was observed at rs1594318-C for primary teeth [intronic within ALLC, odds ratio (OR) 0.85, effect allele frequency (EAF) 0.60, P 4.13e-8] and rs7738851-A (intronic within NEDD9, OR 1.28, EAF 0.85, P 1.63e-8) for permanent teeth. Consortium-wide estimated heritability of caries was low [h2 of 1% (95% CI: 0%: 7%) and 6% (95% CI 0%: 13%) for primary and permanent dentitions, respectively] compared with corresponding within-study estimates [h2 of 28% (95% CI: 9%: 48%) and 17% (95% CI: 2%: 31%)] or previously published estimates. This study was designed to identify common genetic variants with modest effects which are consistent across different populations. We found few single variants associated with caries status under these assumptions. Phenotypic heterogeneity between cohorts and limited statistical power will have contributed; these findings could also reflect complexity not captured by our study design, such as genetic effects which are conditional on environmental exposure.

  • 57.
    Hellman, Urban
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Engström-Laurent, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Larsson, Anders
    Lindqvist, Ulla
    Hyaluronan concentration and molecular mass in psoriatic arthritis: biomarkers of disease severity, resistance to treatment, and outcome2019Ingår i: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: Low molecular mass hyaluronan causes inflammatory processes and can act as a pro-inflammatory cytokine in skin and other sites of activity in psoriatic arthritis (PsA). This study investigated whether the molecular mass distribution of hyaluronan (HA) in skin and the quantity of circulating HA are related to the clinical inflammatory picture in PsA with active disease and to the effect of treatment with anti-tumour necrosis factor-α (anti-TNF-α) adalimumab.

    Methods: Twenty patients with TNF-α-naïve active polyarticular PsA were included in this prospective clinical trial of treatment with 40 mg s.c. adalimumab according to standard procedure. Clinical activity, patients’ assessments, and skin biopsies were captured at inclusion and at the 12 week follow-up. Ten healthy individuals were recruited for comparison of HA analyses. Histochemistry of skin inflammation, serum HA, and molecular mass of HA were determined.

    Results: Overall improvements in clinical parameters were observed. Eight of 18 patients reached minimum disease activity after 12 weeks and disease activity was significantly reduced (p < 0.0001). Patients with elevated serum HA values were significantly older, had later onset of arthritis and more deformed joints, still had swollen joints after treatment, and had more circulating inflammatory biomarkers. More severe disease pathology showed a wide spectrum of high-molecular-mass HA accompanied by low mass HA. The treatment appears partly to normalize the HA mass distribution.

    Conclusion: HA concentration and mass seem to be two possible factors in the inflammatory pathology of PsA acting as biomarkers for disease severity, resistance to treatment, and worse outcome.

  • 58.
    Hemberg, Anders
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap.
    Holmberg, H.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Norberg, Margareta
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Nordin, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap.
    Tobacco use is not associated with groin hernia repair, a population-based study2017Ingår i: Hernia, ISSN 1265-4906, E-ISSN 1248-9204, Vol. 21, nr 4, s. 517-523Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose The pathogenesis of groin hernia is not fully understood and some suggested risk factors are debatable. This population-based study evaluates the association between groin hernia repair and tobacco use. Method An observational study based on register linkage between the Swedish Hernia Register and the Vasterbotten Intervention Program (VIP). All primary groin hernia repairs performed from 2001 to 2013 in the county of Vasterbotten, Sweden, were included. Results VIP provided data on the use of tobacco in 102,857 individuals. Neither smoking nor the use of snus, increased the risk for requiring a groin hernia repair. On the contrary, heavy smoking decreased the risk for men, HR 0.75 (95% CI 0.58-0.96), as did having a BMI over 30 kg/m 2 HR (men) 0.33 (95% CI 0.27-0.40). Conclusion Tobacco use is not a risk factor for requiring a groin hernia repair, whereas having a low BMI significantly increases the risk.

  • 59.
    Henein, Michael Y
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Grönlund, Christer
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Tossavainen, Erik
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Söderberg, Stefan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Gonzalez, Manuel
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Lindqvist, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Klinisk fysiologi.
    Right and left heart dysfunction predict mortality in pulmonary hypertension2017Ingår i: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 37, nr 1, s. 45-51Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In pulmonary hypertension (PH), the right heart dysfunction is a strong predictor of adverse clinical outcome, while the role of the left heart is not fully determined. The aim of this study was to identify predictors of mortality in precapillary PH including measures of both right and left heart function. We studied 34 patients (mean age 64 ± 13, range 31-82 years, 24 females) with precapillary PH, all of whom underwent detailed Doppler echocardiographic examination of the right and left heart function using conventional and speckle-tracking echocardiography. Patients were followed up for up to 8 years (mean 4·2 ± 1·9 years). At follow-up, 16 patients survived. Left ventricular (LV) filling time (P = 0·007), pulmonary artery acceleration time (P = 0·009), right atrial pressure (RAP) (P<0·001) and tricuspid regurgitation (TR) severity (P = 0·007) were worse in the deceased group. RV global longitudinal strain (GLS) (P = 0·001), RAP (P≤0·001), LV filling time (P<0·001) and TR severity (P<0·001) were the most accurate predictors, having the largest AUC (>0·65) and carried the highest risk for mortality (P<0·001 for all). The strongest predictors of mortality in precapillary PH indirectly reflect both left and right heart dysfunction including atrial structure and function disturbances. While an interaction pattern is observed, it needs to be confirmed in a larger cohort.

  • 60.
    Henein, Michael Y.
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Suhr, Ole B.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Arvidsson, Sandra
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Klinisk fysiologi.
    Pilebro, Björn
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Westermark, Per
    Hörnsten, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Klinisk fysiologi.
    Lindqvist, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Reduced left atrial myocardial deformation irrespective of cavity size: a potential cause for atrial arrhythmia in hereditary transthyretin amyloidosis2018Ingår i: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 25, nr 1, s. 46-53Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Cardiac amyloidosis (CA) is a myocardial disease and commonly under-diagnosed condition. In CA patients, atrial fibrillation might occur in the absence of left atrial (LA) enlargement.

    OBJECTIVES: The aim of this study is to assess LA size and function, and its relationship with atrial arrhythmia in patients with hereditary transthyretin amyloidosis (ATTR).

    METHODS: Forty-six patients with confirmed ATTR amyloidosis on abdominal biopsy were studied. Assessment with 2D echocardiography and 2D strain showed 31 patients had increased LV wall thickness (LVWT) (septal thickness >12 mm), and 15 had normal LVWT. In addition to conventional measurements, LV and LA global longitudinal strain (GLS%) and strain rate (SR) were obtained. Western blot analysis was done to assess fibril type. ATTR patients with increased LVWT were compared with 23 patients with hypertrophic cardiomyopathy (HCM) and 31 healthy controls. ATTR amyloidosis patients also underwent 24 hour Holter monitoring to determine the presence of atrial arrhythmia.

    RESULTS: Atrial deformation during atrial systole was reduced in ATTR amyloidosis patients with increased LVWT independent of LA size and in contrast to HCM. Twenty of the ATTR amyloidosis patients (54%) had ECG evidence of significant atrial arrhythmic events. LA strain rate, during atrial systole, was the only independent predictor of atrial arrhythmia (β = 3.28, p = .012).

    CONCLUSION: In ATTR cardiomyopathy with increased LVWT, LA myocardial function is abnormal, irrespective of atrial cavity size. Reduced LA myocardial SR during atrial systole, irrespective of cavity volume, E/e' and LV deformation, is also a strong predictor for atrial arrhythmic events.

  • 61. Henschke, Nicholas
    et al.
    Mirny, Anna
    Haafkens, Joke A.
    Ramroth, Heribert
    Padmawati, Siwi
    Bangha, Martin
    Berkman, Lisa
    Trisnantoro, Laksono
    Blomstedt, Yulia
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Becher, Heiko
    Sankoh, Osman
    Byass, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Kinsman, John
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Strengthening capacity to research the social determinants of health in low-and middle-income countries: lessons from the INTREC programme2017Ingår i: BMC Public Health, ISSN 1471-2458, E-ISSN 1471-2458, Vol. 17, artikel-id 514Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The INDEPTH Training & Research Centres of Excellence (INTREC) collaboration developed a training programme to strengthen social determinants of health (SDH) research in low-and middle-income countries (LMICs). It was piloted among health-and demographic researchers from 9 countries in Africa and Asia. The programme followed a blended learning approach and was split into three consecutive teaching blocks over a 12month period: 1) an online course of 7 video lectures and assignments on the theory of SDH research; 2) a 2-week qualitative and quantitative methods workshop; and 3) a 1-week data analysis workshop. This report aims to summarise the student evaluations of the pilot and to suggest key lessons for future approaches to strengthen SDH research capacity in LMICs. Methods: Semi-structured interviews and questionnaires with 24 students from 9 countries in Africa and Asia were used to evaluate each teaching block. Information was collected about the students' motivation and interest in studying SDH, any challenges they faced during the consecutive teaching blocks, and suggestions they had for future courses on SDH. Results: Of the 24 students who began the programme, 13 (54%) completed all training activities. The students recognised the need for such a course and its potential to improve their skills as health researchers. The main challenges with the online course were time management, prior knowledge and skills required to participate in the course, and the need to get feedback from teaching staff throughout the learning process. All students found the face-to-face workshops to be of high quality and value for their work, because they offered an opportunity to clarify SDH concepts taught during the online course and to gain practical research skills. After the final teaching block, students felt they had improved their data analysis skills and were better able to develop research proposals, scientific manuscripts, and policy briefs. Conclusions: The INTREC programme has trained a promising cadre of health researchers who live and work in LMICs, which is an essential component of efforts to identify and reduce national and local level health inequities. Time management and technological issues were the greatest challenges, which can inform future attempts to strengthen research capacity on SDH.

  • 62.
    Holmlund, Petter
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Johansson, Elias
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Qvarlander, Sara
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Wåhlin, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Ambarki, Khalid
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Koskinen, Lars-Owe D.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Jugular vein collapse in upright and its relation to intracranial pressure regulation2017Ingår i: Journal of Cerebral Blood Flow and Metabolism, ISSN 0271-678X, E-ISSN 1559-7016, Vol. 37, s. 297-297Artikel i tidskrift (Refereegranskat)
  • 63.
    Huber, Daniel
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Henriksson, Robin
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Jakobsson, Stina
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Mooe, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Nurse-led telephone-based follow-up of secondary prevention after acute coronary syndrome: One-year results from the randomized controlled NAILED-ACS trial2017Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, nr 9, artikel-id e0183963Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background. Secondary prevention after acute coronary syndrome (ACS) could reduce morbidity and mortality, but guideline targets are seldom reached. We hypothesized that nurse-led telephone- based intervention would increase adherence.

    Methods. The NAILED ACS trial is a prospective, controlled, randomized trial. Patients admitted for ACS at Ostersund hospital, Sweden, were randomized to usual follow-up by a general practitioner or a nurse-led intervention. The intervention comprised telephone follow-up after 1 month and then yearly with lifestyle counselling and titration of medications until reaching target values for LDL-C (< 2.5 mmol/L) and blood pressure (BP; < 140/90 mmHg) or set targets were deemed unachievable. This is a 12-month exploratory analysis of the intervention.

    Results. A total of 768 patients (396 intervention, 372 control) completed the 12-month follow-up. After titration at the 1-month follow-up, mean LDL-C was 0.38 mmol/L (95% CI 0.28 to 0.48, p< 0.05), mean systolic BP 7 mmHg (95% CI 4.5 to 9.2, p< 0.05), and mean diastolic BP 4 mmHg (95% CI 2.4 to 4.1, p< 0.05) lower in the intervention group. Target values for LDL-C and systolic BP were met by 94.1% and 91.9% of intervention patients and 68.4% and 65.6% of controls (p< 0.05). At 12 months, mean LDL was 0.3 mmol/L (95% CI 0.1 to 0.4, p < 0.05), systolic BP 1.5 mmHg (95% CI -1.0 to 4.1, p = 0.24), and mean diastolic BP 2.1 mmHg (95% CI 0.6 to 3.6, p < 0.05) lower in the intervention group. Target values for LDL-C and systolic BP were met in 77.7% and 68.9% of intervention patients and 63.2% and 63.7% of controls (p< 0.05 and p = 0.125).

    Conclusion. Nurse-led telephone-based secondary prevention was significantly more efficient at improving LDL-C and diastolic BP levels than usual care. The effect of the intervention declined between 1 and 12 months. Further evaluation of the persistence to the intervention is needed.

  • 64.
    Hägglund, Lena
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för omvårdnad.
    Boman, Kurt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin. Department of Medicine-Geriatric, Skellefteå County Hospital, Skellefteå, Sweden.
    Brännström, Margareta
    Umeå universitet, Medicinska fakulteten, Institutionen för omvårdnad.
    A mixed methods study of Tai Chi exercise for patients with chronic heart failure aged 70 years and older2018Ingår i: Nursing Open, E-ISSN 2054-1058, Vol. 5, nr 2, s. 176-185Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aims and objectives

    This study aimed to evaluate Tai Chi group training among patients with chronic heart failure (CHF) aged 70 years and older.

    Background

    Physical activity is recommended for CHF treatment. Tai Chi is found to be beneficial to different patient groups, although few studies focus on older patients with CHF.

    Design

    A mixed methods study. Participants were randomly assigned to Tai Chi training twice a week for 16 weeks (= 25) or control (= 20). Quantitative data were collected at baseline, at the end of the training period and 6 months after training, assessing self-rated fatigue and quality of life, natriuretic peptides and physical performance. Individual qualitative interviews were conducted with participants (= 10) in the Tai Chi training group.

    Results

    No statistical differences between the Tai Chi training group and the control group in quality of life or natriuretic peptides was found. After 16 weeks, the training group tended to rate more reduced activity and the control group rated more mental fatigue. Participants in the training group rated increased general fatigue at follow-up compared with baseline. Qualitative interviews showed that Tai Chi training was experienced as a new, feasible and meaningful activity. The importance of the leader and the group was emphasized. Improvements in balance were mentioned and there was no physical discomfort.

    Conclusion

    Tai Chi was experienced as a feasible and meaningful form of physical exercise for patients with CHF aged over 70 years despite lack of achieved health improvement. Further investigations, using feasibility and meaningfulness as outcome variables seems to be useful.

  • 65.
    Hällgren, Oskar
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Svenmarker, Staffan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Appelblad, Micael
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Implementing a Statistical Model for Protamine Titration: Effects on Coagulation in Cardiac Surgical Patients2017Ingår i: Journal of Cardiothoracic and Vascular Anesthesia, ISSN 1053-0770, E-ISSN 1532-8422, Vol. 31, nr 2, s. 516-521Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVES: To implement a statistical model for protamine titration. DESIGN: Prospective randomized trial. SETTING: University hospital. PARTICIPANTS: Sixty (n = 30+30) patients scheduled for elective coronary artery bypass surgery were randomly assigned to 2 groups. INTERVENTIONS: Protamine dose calculated according to an algorithm established from a statistical model or to a fixed protamine-heparin dose ratio (1:1). MEASUREMENTS AND MAIN RESULTS: Both groups demonstrated comparable patient demographics and intraoperative data. Coagulation effects were evaluated using rotational thromboelastometry. Using the statistical model reduced (p<0.01) the protamine dose from 426±43 mg to 251±66 mg, followed by significantly (p<0.01) shorter intrinsic clotting time (208±29 seconds versus 244±52 seconds) and stronger clot firmness (p = 0.01), and effects on indices of extrinsic or fibrinogen coagulation pathways were insignificant. Test of residual heparin was negative in all patients after protamine administration, aligned with insignificant (p = 0.27) intergroup heparinase-verified clotting time differences. CONCLUSIONS: The statistical model for protamine titration is clinically feasible and protects the patient from exposure to excessive doses of protamine, with advantageous effects on coagulation as measured using rotational thromboelastometry. Significance regarding clinical outcome is yet to be defined.

  • 66. Hållmarker, Ulf
    et al.
    Lindbäck, Johan
    Michaëlsson, Karl
    Ärnlöv, Johan
    Åsberg, Signild
    Wester, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin. Department Clinical Science, Karolinska Institute, Danderyds Hospital, Stockholm, Sweden.
    Hellberg, Dan
    Lagerqvist, Bo
    James, Stefan
    Survival and incidence of cardiovascular diseases in participants in a long-distance ski race (Vasaloppet, Sweden) compared with the background population2018Ingår i: European Heart Journal - Quality of Care and Clinical Outcomes, ISSN 2058-5225, E-ISSN 2058-1742, Vol. 4, nr 2, s. 91-97Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We studied the relationship between taking part in a long-distance ski race and incidence of cardiovascular diseases (CVDs) to address the hypothesis that lifestyle lowers the incidence. A cohort of 399 630 subjects in Sweden, half were skiers in the world's largest ski race, and half were non-skiers. Non-skiers were frequency matched for sex, age, and year of race. Individuals with severe diseases were excluded. The endpoints were death, myocardial infarction, or stroke. The subjects were followed up for a maximum of 21.8 years and median of 9.8 years. We identified 9399 death, myocardial infarction, or stroke events among non-skiers and 4784 among the Vasaloppet skiers. The adjusted hazard ratios (HRs) comparing skiers and non-skiers were 0.52 [95% confidence interval (CI) 0.49-0.54] for all-cause mortality, 0.56 (95% CI 0.52-0.60) for myocardial infarction and 0.63 (95% CI 0.58-0.67) for stroke and for all three outcomes 0.56 (95% CI 0.54-0.58). The results were consistent across subgroups: age, sex, family status, education, and race year. For skiers, a doubling of race time was associated with a higher age-adjusted risk of 19%, and male skiers had a doubled risk than female skiers, with a HR 2.06 (95% CI 1.89-2.41). The outcome analyses revealed no differences in risk of atrial fibrillation between skiers and non-skiers. This large cohort study provides additional support for the hypothesis that individuals with high level of physical activity representing a healthy lifestyle, as evident by their participation in a long-distance ski race, have a lower risk of CVD or death.

  • 67.
    Högberg, Cecilia
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Karling, Pontus
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Rutegård, Jörgen
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap.
    Lilja, Mikael
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Diagnosing colorectal cancer and inflammatory bowel disease in primary care: The usefulness of tests for faecal haemoglobin, faecal calprotectin, anaemia and iron deficiency: A prospective study2017Ingår i: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 52, nr 1, s. 69-75Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: Abdominal complaints are common reasons to consult primary care but they are seldom caused by colorectal cancer (CRC), high-risk adenomas (HRAs), or inflammatory bowel disease (IBD). Reliable diagnostic aids would be helpful in deciding which patients to refer for bowel imaging. Our aim was to assess the value of a faecal immunochemical test (FIT) and a faecal calprotectin (FC) test in detecting CRC, HRAs and IBD in primary care, and the value of combining these tests with anaemia and iron-deficiency tests.

    MATERIALS AND METHODS: This prospective study included 373 consecutive patients that received a FIT or a FC test ordered by a primary care physician. We collected samples for FITs, FC tests, full blood counts and iron-deficiency tests. Physicians were instructed to refer patients with a positive FIT or FC test (cut-off ≥100μg/g) for bowel imaging. The patients' presenting symptoms were recorded. Patients were followed for 2 years.

    RESULTS: The best test for detecting CRC and IBD was the combination of the FIT and haemoglobin concentration. This test had a sensitivity, specificity, positive predictive value and negative predictive value of 100%, 61.7%, 11.7% and 100%, respectively. The FIT detected a significantly larger proportion of CRC, HRAs and IBD than the FC test (0.92 versus 0.46, 95% confidence interval 0.22-0.67).

    CONCLUSION: A negative FIT combined with a normal haemoglobin concentration could rule out CRC and IBD with a high degree of safety. This could be useful in prioritising referrals for bowel imaging from primary care.

  • 68.
    Högberg, Cecilia
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Söderström, Lars
    Lilja, Mikael
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Faecal immunochemical tests for the diagnosis of symptomatic colorectal cancer in primary care: the benefit of more than one sample2017Ingår i: Scandinavian Journal of Primary Health Care, ISSN 0281-3432, E-ISSN 1502-7724, Vol. 35, nr 4, s. 369-372Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: Faecal immunochemical tests (FITs) are used to screen for colorectal cancer (CRC) and as diagnostic aids in symptomatic patients. However, the number of samples per FIT varies. It is unclear if there is any advantage to analyse multiple-sample FITs in symptomatic patients.

    Design and setting: This is a post hoc analysis of a retrospective study that included all cases of CRC and adenomas with high-grade dysplasia (HGD) between 2005 and 2009 in the county of Jamtland, Sweden.

    Subjects: All patients with CRC and adenomas with HGD that initially presented with symptoms to primary care and delivered FITs.

    Main outcome measure: The likelihood of a positive FIT in cases of CRC and adenomas with HGD; when analysing one, two or three samples.

    Results: Of 195 patients, 160 delivered three-sample FITs. Using the 139 cases in which at least one sample was positive, the likelihood of detecting a positive sample upon analysis of only one of the three samples was 0.91 (95% CI: 0.85-0.95), indicating that 13 positive cases may have been missed.

    Conclusion: Use of a one-sample FIT instead of a three-sample FIT as a diagnostic aid may result in the missing of one tenth of symptomatic CRCs and adenomas with HGD.

  • 69.
    Höglund, Niklas
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Sahlin, Carin
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Kesek, Milos
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Jensen, Steen M.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Franklin, Karl A.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Cardioversion of atrial fibrillation does not affect obstructive sleep apnea2017Ingår i: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 122, nr 2, s. 114-118Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Sleep apnea is common in patients with atrial fibrillation, but the effect of the cardioversion of atrial fibrillation to sinus rhythm on central and obstructive apneas is mainly unknown. The primary aim of the study was to analyze the association between cardioversion of atrial fibrillation and sleep apneas, to investigate whether obstructive or central sleep apneas are reduced following cardioversion. A secondary objective was to study the effect on sleep quality. Methods: Twenty-three patients with atrial fibrillation were investigated using overnight polysomnography, including esophagus pressure monitoring and ECG, before and after the cardioversion of persistent atrial fibrillation. Results: Obstructive sleep apnea occurred in 17/23 patients (74%), and central sleep apnea in 6/23 patients (26%). Five patients had both obstructive and central sleep apnea. Sinus rhythm at follow-up was achieved in 16 patients. The obstructive apnea-hypopnea index, central apnea-hypopnea index, and the number of patients with obstructive or central sleep apnea did not differ before and after restoration of sinus rhythm. Sleep time, sleep efficiency, time in different sleep stages, and subjective daytime sleepiness were normal and unaffected by cardioversion. Conclusions: Both obstructive and central sleep apneas are highly prevalent in patients with persistent atrial fibrillation. Obstructive sleep apneas are unaffected by the cardioversion of atrial fibrillation to sinus rhythm. The sleep pattern is normal and unaffected by cardioversion in patients with atrial fibrillation. Clinical Trial Registration: Trial number NCT00429884.

  • 70.
    Jashari, Fisnik
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Ibrahimi, Pranvera
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Bajraktari, Gani
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Grönlund, Christer
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Wester, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin. Department of Clinical Sciences, Danderyds Hospital, Karolinska Institute, Stockholm, Sweden.
    Henein, Michael Y
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Carotid plaque echogenicity predicts cerebrovascular symptoms: a systematic review and meta-analysis2016Ingår i: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 23, nr 7, s. 1241-1247Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background and purpose: Many reports have shown an association between hypoechoic (echolucent) carotid atherosclerotic plaques and unstable features. In this meta-analysis our aim was to determine the role of carotid plaque echogenicity in predicting future cerebrovascular (CV) symptoms.

    Methods: Electronic databases (PubMed, MEDLINE, EMBASE and Cochrane Center Register) up to September 2015 were systematically searched. Studies with ultrasound-based characterization of carotid artery plaque echogenicity and its association with focal neurological symptoms of vascular origin were eligible for analysis. In the meta-analysis, heterogeneity was measured usingI2 statistics and publication bias was evaluated using the Begg–Mazumdar test. In addition several comparisons between subgroups were performed.

    Results: Of 1387 identified reports, eight studies with asymptomatic patients and three studies with symptomatic patients were meta-analyzed. Pooled analysis showed an association between echolucent carotid plaques and future CV events in asymptomatic patients [relative risk 2.72 (95% confidence interval 1.86–3.96)] and recurrent symptoms in symptomatic patients [relative risk 2.97 (95% confidence interval 1.85–4.78)]. The association was preserved for all stenosis degrees in asymptomatic patients, whilst patients with echolucent plaques and severe stenosis were at higher risk of future events. Also, computer-assisted methods for assessment of carotid plaque echogenicity and studies analyzing ultrasound data collected after the year 2000 showed better prediction.

    Conclusions: In asymptomatic and symptomatic patients, analysis of carotid plaque echogenicity could identify those at high risk of CV events.

  • 71.
    Jashari, Fisnik
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Ibrahimi, Pranvera
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Johansson, Elias
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Grönlund, Christer
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Wester, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin. Department of Clinical Sciences, Danderyds Hospital, Karolinska Institute, Stockholm, Sweden.
    Henein, Michael Y.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Carotid IM-GSM is better than IMT for identifying patients with multiple arterial disease2018Ingår i: Scandinavian Cardiovascular Journal, ISSN 1401-7431, E-ISSN 1651-2006, Vol. 52, nr 2, s. 93-99Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective. Atherosclerosis is a systemic inflammatory disease that can affect more than one arterial bed simultaneously. The aim of this study was to determine the relationship between ultrasound markers of atherosclerosis and multiple arterial disease. Design. We have included 87 currently asymptomatic carotid disease patients (mean age 69 +/- 6 year, 34% females) in this study. Intima media thickness (IMT) and intima media-grey scale median (IM-GSM) were measured in the common carotid artery (CCA), and correlated with previous and/or current atherosclerotic vascular disease in the coronary, carotid and lower extremities. Patients were divided into three groups: (1) asymptomatic, (2) previous symptoms in one arterial territory and (3) previous symptoms in multiple arterial territories. Results. Patients with previous disease in the coronary arteries had higher IMT (p=.034) and lower IM-GSM (p<.001), and those with prior stroke had lower IM-GSM (p=.007). Neither IMT nor IM-GSM was different between patients with and without previous lower extremity vascular disease. IM-GSM was significantly different between groups, it decreased significantly with increasing number of arterial territories affected (37.7 +/- 15.4 vs. 29.3 +/- 16.4 vs. 20.7 +/- 12.9) p<.001, for asymptomatic, symptoms in one and in multiple arterial systems, respectively. Conventional IMT was not significantly different between groups p=.49. Conclusion. Carotid IMT was higher and IM-GSM lower in patients with symptomatic nearby arterial territories but not in those with peripheral disease. In contrast to conventional IMT, IM-GSM can differentiate between numbers of arterial territories affected by atherosclerosis, suggesting that it is a better surrogate for monitoring multiple arterial territory disease.

  • 72.
    Johagen, Daniel
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Svenmarker, Pontus
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysik.
    Jonsson, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin. Department of Biomedical Engineering and Informatics, Umeå University, Umeå, Sweden.
    Svenmarker, Staffan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    A microscopic view of gaseous microbubbles passing a filter screen2017Ingår i: International Journal of Artificial Organs, ISSN 0391-3988, E-ISSN 1724-6040, Vol. 40, nr 9, s. 498-502Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose: The aim of this study was to investigate the filtration efficacy of a 38-µm 1-layer screen filter based on Doppler registrations and video recordings of gaseous microbubbles (GME) observed in a microscope.

    Methods: The relative filtration efficacy (RFE) was calculated from 20 (n = 20) sequential bursts of air introduced into the Plasmodex® primed test circuit.

    Results: The main findings indicate that the RFE decreased (p = 0.00), with increasing flow rates (100-300 mL/min) through the filter screen. This reaction was most accentuated for GME below the size of 100 µm, where counts of GME paradoxically increased after filtration, indicating GME fragmentation. For GME sized between 100-250 µm, the RFE was constantly >60%, independently of the flow rate level. The video recording documenting the GME interactions with the screen filter confirmed the experimental findings.

    Conslusions: The 38-µm 1-layer screen filter investigated in this experimental setup was unable to trap gaseous microbubbles effectively, especially for GME below 100 µm in size and in conjunction with high flow rates.

  • 73.
    Johansson, Cecilia
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Dahlqvist, Erik
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Andersson, Jonas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Jansson, Jan-Håkan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Johansson, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Incidence, type of atrial fibrillation and risk factors for stroke: a population-based cohort study2017Ingår i: Clinical Epidemiology, ISSN 1179-1349, E-ISSN 1179-1349, Vol. 9, s. 53-62Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose: The aims of this study were to estimate the incidence of atrial fibrillation and atrial flutter (AF), to assess the presence of provoking factors and risk factors for stroke and systemic embolism, and to determine the type of AF in patients with first-diagnosed AF. Patients and methods: This cohort study was performed in northern Sweden between January 1, 2011 and December 31, 2012. Diagnosis registries were searched for the International Classification of Diseases-10 code for AF (I48) to identify cases of incident AF. All AF diagnoses were electrocardiogram-verified. Data pertaining to provoking factors, type of AF and presence of risk factors for stroke and systemic embolism according to the CHA(2)DS(2)-VASc score were obtained from medical records. Results: The incidence of AF in the entire population was 4.0 per 1,000 person-years. The incidence was 27.5 per 1,000 person-years in patients aged >= 80 years. A total of 21% of all patients had a provoking factor in association with the first-diagnosed episode of AF. The CHA(2)DS(2)-VASc score was 2 or higher in 81% of the patients. Permanent AF was the most common type of AF (29%). Conclusion: There was a considerable increase in the incidence of AF with age, and a provoking factor was found in one-fifth. The most common type of AF was permanent AF. Four in five patients had a CHA(2)DS(2)-VASc score of 2 or more.

  • 74.
    Johansson, Kristina
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Jansson, Jan-Håkan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Johansson, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Bylesjö, Ingemar
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Nilsson, Torbjörn K
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Eliasson, Mats
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Söderberg, Stefan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Lind, Marcus
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Factor XII as a Risk Marker for Hemorrhagic Stroke: A Prospective Cohort Study2017Ingår i: Cerebrovascular diseases extra, ISSN 1664-5456, Vol. 7, nr 1, s. 84-94Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Coagulation factor XII (FXII) is involved in pathological thrombus formation and is a suggested target of anticoagulants. It is unclear whether FXII levels are correlated with cardiovascular risk factors and whether they are associated with myocardial infarction or ischemic or hemorrhagic stroke. The aim of this study was to investigate the correlation between FXII and cardiovascular risk factors in the general population. We also aimed to study the associations between FXII levels and future myocardial infarction and ischemic and hemorrhagic stroke.

    METHODS: This prospective cohort study measured FXII levels in 1,852 randomly selected participants in a health survey performed in northern Sweden in 1994. Participants were followed until myocardial infarction, stroke, death, or until December 31, 2011.

    RESULTS: During the median follow-up of 17.9 years, 165 individuals were diagnosed with myocardial infarction, 108 with ischemic stroke, and 30 with hemorrhagic stroke. There were weak correlations between FXII and body mass index, cholesterol, and hypertension. There was no association between FXII and myocardial infarction or ischemic stroke, neither in univariable Cox regression analysis nor after adjustment for age, sex, smoking, body mass index, cholesterol, hypertension, and diabetes. In univariable Cox regression analysis, the hazard ratio for the association between FXII levels and hemorrhagic stroke was 1.42 per SD (95% confidence interval: 0.99-2.05). In the multivariable model, higher levels of FXII were associated with increased risk of hemorrhagic stroke (hazard ratio 1.51 per SD; 95% confidence interval: 1.03-2.21).

    CONCLUSION: We found an independent association between FXII levels and the risk of hemorrhagic stroke, but not between FXII levels and ischemic stroke or myocardial infarction.

  • 75.
    Johansson, Kristina
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Jansson, Jan-Håkan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Johansson, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Wiklund, Per-Gunnar
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Nilsson, Torbjörn K.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Lind, Marcus
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    D-Dimer is associated with first-ever intracerebral hemorrhage: a nested case-control study2018Ingår i: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 49, nr 9, s. 2034-2039Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background and Purpose - Hypertension is the most important risk factor for intracerebral hemorrhage (ICH), but further characterization is needed for groups at high risk of ICH. One way to predict the risk of developing a disease is with plasma biomarkers. This study aimed to investigate the association between the biomarker, D-dimer, and ICH risk.

    Methods - This population-based, nested case-control study was conducted using data from 2 population-based surveys; the Vasterbotten Intervention Programme and MONICA Northern Sweden (Monitoring Trends and Determinants in Cardiovascular Disease). All participants underwent a health examination and blood sampling at baseline before the event. Cases (n=141) were diagnosed with a first-ever ICH between 1985 and March 2007. One or 2 controls (n=255) were matched to each case.

    Results - The median age was 60 years; 39% of participants were women; and the median time from blood sampling to ICH was 5.2 years. When D-dimer was evaluated as a continuous variable, it was significantly associated with ICH. After multivariable adjustment (for hypertension, body mass index, cholesterol levels, diabetes mellitus, and smoking), the odds ratio was 1.36 per SD of D-dimcr (95% CI, 1.05-1.77). When participants were stratified in 3 groups according to time from blood sampling at health examination to ICH, we found that the association between D-dimer levels and ICH was most pronounced in individuals with the shortest time from blood sampling to ICH event (<3.5 years; odds ratio, 1.78; 95% CI, 1.05-3.05).

    Conclusions - High plasma concentrations of D-dimer were associated with increased risk of a future ICH, after adjusting for cardiovascular risk factors. This association was predominantly driven by the cases with the shortest time from blood sampling to ICH event.

  • 76.
    Jonsson, Anna
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Norberg, Helena
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Bergdahl, Ellinor
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Lindmark, Krister
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Obstacles to mineralocorticoid receptor antagonists in a community-based heart failure population2018Ingår i: Cardiovascular therapeutics, ISSN 1755-5914, Vol. 36, nr 5, artikel-id e12459Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    AIM: Previous studies and national assessments indicate an undertreatment of mineralocorticoid receptor antagonists (MRA) in heart failure with reduced ejection fraction (HFrEF). This study aimed to investigate why MRA is not used to full extent.

    METHODS: A complete community-based heart failure population was studied. Several variables were collected, and medical records were scrutinized to identify reasons for not prescribing MRA.

    RESULTS: Of 2029 patients, 812 had EF ≤40%. Five hundred and fifty-three patients (68%) tried MRA at some point but 184 of these (33%) discontinued therapy. There were 259 patients that never tried MRA with 177 with a listed explanation or contraindication. Eighty-two patients, 10% of the total HFrEF population, had no clear contraindications. They were older and had less HF hospitalizations compared to patients on MRA (P < 0.05) and 32% did not have any follow-up at the cardiology clinic. Contraindications to MRA were renal dysfunction (93 patients), hypotension (28 patients), and hyperkalemia (25 patients). Only six patients had hyperkalemia without renal dysfunction. Of the patients with renal dysfunction, 66 (72%) had eGFR >30 mL/min.

    CONCLUSIONS: The reasons why MRA are underutilized were mainly because of contraindications. However, the data suggest that physicians are overly cautious about moderately reduced kidney function. There seems to be a 10%-18% avoidable undertreatment with MRA, especially for elderly patients that are admitted to the hospital for other reasons than heart failure. This suggests that patients with heart failure would benefit from routine follow-up at a cardiology clinic.

  • 77.
    Jonsson, Per
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Lindmark, Lorentz
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Axelsson, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Karlsson, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Lundberg, Lennart
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Stegmayr, Bernd
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Formation of Blood Foam in the Air Trap During Hemodialysis Due to Insufficient Automatic Priming of Dialyzers2018Ingår i: Artificial Organs, ISSN 0160-564X, E-ISSN 1525-1594, Vol. 42, nr 5, s. 533-539Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We were encouraged to investigate the reasons for large amounts of foam observed in bloodlines during hemodialysis (HD). Foam was visible in the venous air trap within the Artis Gambro dialysis device. Estimates of the extent of foam were graded (0no foam, 10extensive foam) by two persons that were blind to the type of dialyzer used. Thirty-seven patients were involved in the dialysis procedures. Consecutive dialyses were graded using dialyzers from Fresenius Medical Care (CorDiax dialyzers that were used for high flux HDFX80 and FX100, and for hemodiafiltrationFX1000). The extracorporeal circuit was primed automatically by dialysate using Gambro Artis software 8.15 006 (Gambro, Dasco, Medolla Italy, Baxter, Chicago, IL, USA). The priming volume recommended by the manufacturer was 1100 mL, whereas our center uses 1500 mL. Extensive amounts of blood foam were visual in the air traps. Although the manufacturer recommended extension of priming volume up to 3000 mL, this did not eliminate the foam. Microbubble measurement during HD revealed the air to derive from the dialyzers. When changing to PF210H dialyzers (Baxter) and using a priming volume of 1500 mL, the foam was significantly less (P<0.01). The extent of foam correlated with the size of the FX-dialyzer surface (P=0.002). The auto-priming program was updated to version 8.21 by the manufacturer and the extent of foam in the air trap using FX dialyzers was now reduced and there was no longer a difference between FX and PF dialyzers, although less foam was still visible in the venous air trap during several dialyses. In conclusion, this study urgently calls attention to blood foam development in the venous air trap when using Artis devices and priming software 8.15 in combination with Fresenius dialyzers. Updated auto-priming software (version 8.21) of Artis should be requested to reduce the extent of foam for the Fresenius dialyzers. Other interactions may also be present. We recommend further studies to clarify these problems. Meanwhile caution is warranted for the combined use of dialysis devices and dialyzers with incompatible automatic priming.

  • 78. Justice, Anne E.
    et al.
    Karaderi, Tugce
    Highland, Heather M.
    Young, Kristin L.
    Graff, Mariaelisa
    Lu, Yingchang
    Turcot, Valerie
    Auer, Paul L.
    Fine, Rebecca S.
    Guo, Xiuqing
    Schurmann, Claudia
    Lempradl, Adelheid
    Marouli, Eirini
    Mahajan, Anubha
    Winkler, Thomas W.
    Locke, Adam E.
    Medina-Gomez, Carolina
    Esko, Tonu
    Vedantam, Sailaja
    Giri, Ayush
    Lo, Ken Sin
    Alfred, Tamuno
    Mudgal, Poorva
    Ng, Maggie C. Y.
    Heard-Costa, Nancy L.
    Feitosa, Mary F.
    Manning, Alisa K.
    Willems, Sara M.
    Sivapalaratnam, Suthesh
    Abecasis, Goncalo
    Alam, Dewan S.
    Allison, Matthew
    Amouyel, Philippe
    Arzumanyanm, Zorayr
    Balkau, Beverley
    Bastarache, Lisa
    Bergmann, Sven
    Bielak, Lawrence F.
    Blueher, Matthias
    Boehnke, Michael
    Boeing, Heiner
    Boerwinkle, Eric
    Boeger, Carsten A.
    Bork-Jensen, Jette
    Bottinger, Erwin P.
    Bowden, Donald W.
    Brandslund, Ivan
    Broer, Linda
    Burt, Amber A.
    Butterworth, Adam S.
    Caulfield, Markj
    Cesana, Giancarlo
    Chambers, John C.
    Chasman, Daniel, I
    Chen, Yii-Der Ida
    Chowdhury, Rajiv
    Christensen, Cramer
    Chu, Audreyy
    Collins, Francis S.
    Cook, James P.
    Cox, Amanda J.
    Crosslin, David S.
    Danesh, John
    de Bakker, Paul I. W.
    de Denus, Simon
    de Mutsert, Renee
    Dedoussis, George
    Demerath, Ellen W.
    Dennis, Joe G.
    Denny, Josh C.
    Di Angelantonio, Emanuele
    Doerr, Marcus
    Drenos, Fotios
    Dube, Marie-Pierre
    Dunning, Alison M.
    Easton, Douglas F.
    Elliott, Paul
    Evangelou, Evangelos
    Farmaki, Aliki-Eleni
    Feng, Shuang
    Ferrannini, Ele
    Ferrieres, Jean
    Florez, Jose C.
    Fornage, Myriam
    Fox, Caroline S.
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin. Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Malmo, Sweden; Department of Nutrition, Harvard School of Public Health, Boston, MA, USA.
    Friedrich, Nele
    Gan, Wei
    Gandin, Ilaria
    Gasparini, Paolo
    Giedraitis, Vilmantas
    Girotto, Giorgia
    Gorski, Mathias
    Grallert, Harald
    Grarup, Niels
    Groves, Megan L.
    Gustafsson, Stefan
    Haessler, Jeff
    Hansen, Torben
    Hattersley, Andrew T.
    Hayward, Caroline
    Heid, Iris M.
    Holmen, Oddgeir L.
    Hovingh, G. Kees
    Howson, Joanna M. M.
    Hu, Yao
    Hung, Yi-Jen
    Hveem, Kristian
    Ikram, M. Arfan
    Ingelsson, Erik
    Jackson, Anne U.
    Jarvik, Gail P.
    Jia, Yucheng
    Jorgensen, Torben
    Jousilahti, Pekka
    Justesen, Johanne M.
    Kahali, Bratati
    Karaleftheri, Maria
    Kardia, Sharon L. R.
    Karpe, Fredrik
    Kee, Frank
    Kitajima, Hidetoshi
    Komulainen, Pirjo
    Kooner, Jaspal S.
    Kovacs, Peter
    Kraemer, Bernhard K.
    Kuulasmaa, Kari
    Kuusisto, Johanna
    Laakso, Markku
    Lakka, Timo A.
    Lamparter, David
    La Nge, Leslie A.
    Langenberg, Claudia
    Larson, Eric B.
    Lee, Nanette R.
    Lee, Wen-Jane
    Lehtimaeki, Terho
    Lewis, Cora E.
    Li, Huaixing
    Li, Jin
    RuifangLi-Gao,
    Lin, Li-An
    Lin, Xu
    Lind, Lars
    Lindstroem, Jaana
    Linneberg, Allan
    Liu, Ching-Ti
    Liu, Dajiang J.
    Luan, Jian'an
    Lyytikainen, Leo-Pekka
    MacGregor, Stuart
    Magi, Reedik
    Mannisto, Satu
    Marenne, Gaelle
    Marten, Jonathan
    Mascal, Nicholas G. D.
    McCarthy, Mark, I
    Meidtner, Karina
    Mihailov, Evelin
    Moilanen, Leena
    Moitry, Marie
    Mook-Kanamori, Dennis O.
    Morgan, Anna
    Morris, Andrew P.
    Mueller-Nurasyid, Martina
    Munroe, Patricia B.
    Narisu, Narisu
    Nelson, Christopher P.
    Neville, Matt
    Ntalla, Ioanna
    Owen, Katharine R.
    Pedersen, Oluf
    Peloso, Gina M.
    Pennell, Craig E.
    Perola, Markus
    James, A.
    Perry, John R. B.
    Pers, Tune H.
    Ewing, Ailith
    Polasek, Ozren
    Rasheed, Asif
    Raulerson, Chelsea K.
    Rauramaa, Rainer
    Reilly, Dermot F.
    Reiner, Alex P.
    Ridker, Paul M.
    Rivas, Manuel A.
    Robertson, Neil R.
    Robino, Antonietta
    Rudan, Igor
    Ruth, Katherine S.
    Saleheen, Danish
    Salomaa, Veikko
    Samani, Nilesh J.
    Schreiner, Pamela J.
    Schulze, Matthias B.
    Scott, Robert A.
    Segura-Lepe, Marcelo
    Sim, Xueling
    Slater, Andrew J.
    Small, Kerrin S.
    Smith, Blair H.
    Smith, Jennifer A.
    Southam, Lorraine
    Spector, Timothy D.
    Speliotes, Elizabeth K.
    Stefansson, Kari
    Steinthorsdottir, Valgerdur
    Stirrups, Kathleen E.
    Strauch, Konstantin
    Stringham, Heather M.
    Stumvoll, Michael
    Sun, Liang
    Surendran, Praveen
    Swart, Karin M. A.
    Tardif, Jean-Claude
    Taylor, Kent D.
    Teumer, Alexander
    Thompson, Deborah J.
    Thorleifsson, Gudmar
    Thorsteinsdottir, Unnur
    Thuesen, Betina H.
    Toenjes, Anke
    Torres, Mina
    Tsafantakis, Emmanouil
    Tuomilehto, Jaakko
    Uitterlinden, Andre G.
    Uusitupa, Matti
    van Duijn, Cornelia M.
    Vanhala, Mauno
    Varma, Rohit
    Vermeulen, Sita H.
    Vestergaard, Henrik
    Vitart, Veronique
    Vogt, Thomas F.
    Vuckovic, Dragana
    Wagenknecht, Lynne E.
    Walker, Mark
    Wallentin, Lars
    Wang, Feijie
    Wang, Carol A.
    Wang, Shuai
    Wareham, N. Icholas J.
    Warren, Helen R.
    Waterworth, Dawn M.
    Wessel, Jennifer
    White, Harvey D.
    Willer, Cristen J.
    Wilson, James G.
    Wood, Andrew R.
    Wu, Ying
    Yaghootkar, Hanieh
    Yao, Jie
    Verges-Armstrong, Laura M.
    Young, Robin
    Zeggini, Eleftheria
    Zhan, Xiaowei
    Zhang, Weihua
    Zhao, Jing Hua
    Zhao, Wei
    Zheng, He
    Zhou, Wei
    Zillikens, M. Carola
    Rivadeneira, Fernando
    Borecki, Ingrid B.
    Pospisilik, J. Andrew
    Deloukas, Panos
    Frayling, Timothy M.
    Lettre, Guillaume
    Mohlke, Karen L.
    Rotter, Jerome, I
    Kutalik, Zoltan
    Hirschhorn, Joel N.
    Cupples, L. Adrienne
    Loos, Ruth J. F.
    North, Kari E.
    Lindgren, Cecilia M.
    O'Connell, Jeffrey R.
    Raitakari, Olli T.
    Lange, Leslie A.
    Uitterlinden, Andr G.
    Grove, Megan L.
    Masca, Nicholas G. D.
    Luan, Jianan
    Wareham, Nicholas J.
    Esko, Tnu
    De Bakker, Paul Iw
    Caulfield, Mark J.
    Mller-Nurasyid, Martina
    Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution2019Ingår i: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 51, nr 3, s. 452-469Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Body-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (validation). We identified 15 common (minor allele frequency, MAF >= 5%) and nine low-frequency or rare (MAF < 5%) coding novel variants. Pathway/gene set enrichment analyses identified lipid particle, adiponectin, abnormal white adipose tissue physiology and bone development and morphology as important contributors to fat distribution, while cross-trait associations highlight cardiometabolic traits. In functional follow-up analyses, specifically in Drosophila RNAi-knockdowns, we observed a significant increase in the total body triglyceride levels for two genes (DNAH10 and PLXND1). We implicate novel genes in fat distribution, stressing the importance of interrogating low-frequency and protein-coding variants.

  • 79. Karlsson, Anna
    et al.
    Cirenajwis, Helena
    Ericson-Lindquist, Kajsa
    Brunnström, Hans
    Reuterswärd, Christel
    Jönsson, Mats
    Ortiz-Villalon, Cristian
    Hussein, Aziz
    Bergman, Bengt
    Vikström, Anders
    Monsef, Nastaran
    Branden, Eva
    Koyi, Hirsh
    de Petris, Luigi
    Micke, Patrick
    Patthey, Annika
    Behndig, Annelie F.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Johansson, Mikael
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Planck, Maria
    Staaf, Johan
    A combined gene expression tool for parallel histological prediction and gene fusion detection in non-small cell lung cancer2019Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, artikel-id 5207Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Accurate histological classification and identification of fusion genes represent two cornerstones of clinical diagnostics in non-small cell lung cancer (NSCLC). Here, we present a NanoString gene expression platform and a novel platform-independent, single sample predictor (SSP) of NSCLC histology for combined, simultaneous, histological classification and fusion gene detection in minimal formalin fixed paraffin embedded (FFPE) tissue. The SSP was developed in 68 NSCLC tumors of adenocarcinoma (AC), squamous cell carcinoma (SqCC) and large-cell neuroendocrine carcinoma (LCNEC) histology, based on NanoString expression of 11 (CHGA, SYP, CD56, SFTPG, NAPSA, TTF-1, TP73L, KRT6A, KRT5, KRT40, KRT16) relevant genes for IHC-based NSCLC histology classification. The SSP was combined with a gene fusion detection module (analyzing ALK, RET, ROS1, MET, NRG1, and NTRK1) into a multicomponent NanoString assay. The histological SSP was validated in six cohorts varying in size (n = 11-199), tissue origin (early or advanced disease), histological composition (including undifferentiated cancer), and gene expression platform. Fusion gene detection revealed five EML4-ALK fusions, four KIF5B-RET fusions, two CD74-NRG1 fusion and three MET exon 14 skipping events among 131 tested cases. The histological SSP was successfully trained and tested in the development cohort (mean AUC = 0.96 in iterated test sets). The SSP proved successful in predicting histology of NSCLC tumors of well-defined subgroups and difficult undifferentiated morphology irrespective of gene expression data platform. Discrepancies between gene expression prediction and histologic diagnosis included cases with mixed histologies, true large cell carcinomas, or poorly differentiated adenocarcinomas with mucin expression. In summary, we present a proof-of-concept multicomponent assay for parallel histological classification and multiplexed fusion gene detection in archival tissue, including a novel platform-independent histological SSP classifier. The assay and SSP could serve as a promising complement in the routine evaluation of diagnostic lung cancer biopsies.

  • 80. Khangure, Simon R.
    et al.
    Benhabib, Hadas
    Machnowska, Matylda
    Fox, Allan J.
    Grönlund, Christer
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Herod, Wendy
    Maggisano, Robert
    Sjöberg, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap.
    Wester, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin. Department of Clinical Sciences, Karolinska Institutet Danderyds Hospital, Stockholm, Sweden.
    Hojjat, Seyed-Parsa
    Hopyan, Julia
    Aviv, Richard I.
    Johansson, Elias
    Carotid near-occlusion frequently has high peak systolic velocity on Doppler ultrasound2018Ingår i: Neuroradiology, ISSN 0028-3940, E-ISSN 1432-1920, Vol. 60, nr 1, s. 17-25Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose: Carotid near-occlusion is a tight atherosclerotic stenosis of the internal carotid artery (ICA) resulting in decrease in diameter of the vessel lumen distal to the stenosis. Near-occlusions can be classified as with or without full collapse, and may have high peak systolic velocity (PSV) across the stenosis, mimicking conventional > 50% carotid artery stenosis. We aimed to determine how frequently near-occlusions have high PSV in the stenosis and determine how accurately carotid Doppler ultrasound can distinguish high-velocity near-occlusion from conventional stenosis.

    Methods: Included patients had near-occlusion or conventional stenosis with carotid ultrasound and CT angiogram (CTA) performed within 30 days of each other. CTA examinations were analyzed by two blinded expert readers. Velocities in the internal and common carotid arteries were recorded. Mean velocity, pulsatility index, and ratios were calculated, giving 12 Doppler parameters for analysis.

    Results: Of 136 patients, 82 had conventional stenosis and 54 had near-occlusion on CTA. Of near-occlusions, 40 (74%) had high PSV (≥ 125 cm/s) across the stenosis. Ten Doppler parameters significantly differed between conventional stenosis and high-velocity near-occlusion groups. However, no parameter was highly sensitive and specific to separate the groups.

    Conclusion: Near-occlusions frequently have high PSV across the stenosis, particularly those without full collapse. Carotid Doppler ultrasound does not seem able to distinguish conventional stenosis from high-velocity near-occlusion. These findings question the use of ultrasound alone for preoperative imaging evaluation.

  • 81.
    Khatami, Alireza
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa. Center for Research and Training in Skin Diseases and Leprosy, Tehran University of Medical Sciences, Tehran, Iran.
    Emmelin, Maria
    Talaee, Rezvan
    Mohammadi, Akram Miramin
    Aghazadeh, Nessa
    Firooz, Alireza
    Stenberg, Berndt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Dermatologi och venereologi. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Lived experiences of patients suffering from acute Old World cutaneous leishmaniasis: A qualitative content analysis study from Iran2018Ingår i: Iranian Journal of Arthropod-Borne Diseases, ISSN 1735-7179, E-ISSN 2008-2517, Vol. 12, nr 2, s. 180-195Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The aim of this study was to explore the experiences of patients who suffer from acute cutaneous leishmaniasis in Iran, focusing on quality of life.

    Methods: The study was conducted at two different sites in Iran in 2010–2011. Individual in-depth interviews were conducted with six men and six women parasitologically confirmed acute cutaneous leishmaniasis. Interviews were recorded, transcribed verbatim, and translated into English. Qualitative content analysis was used for data analysis.

    Results: The participants, aged 23 to 63yr, had mild to severe disease. Based on the analysis four main themes were developed. "Fearing an agonizing disease" reflects patients' experiences of disease development resulting in sadness and depression, "struggling to cope" and "taking on the blame" both illustrate how patients experience living with the disease, which included both felt and enacted stigma as major social concerns. "Longing for being seen and heard" refers to patients' experiences with healthcare as well as their expectations and demands from communities and healthcare to be involved in closing the knowledge and awareness gap.

    Conclusion: Mental and social dimensions of cutaneous leishmaniasis were complex and adversely affected patients' lives by causing psychological burden and limiting their social interactions. Health authorities have to plan programs to increase the disease awareness to prevent the existing stigma to improve patients' social condition and medical care.

  • 82.
    Kindstedt, Elin
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Johansson, Linda
    Palmqvist, Py
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Koskinen Holm, Cecilia
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Kokkonen, Heidi
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Johansson, Ingegerd
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Rantapää-Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Lundberg, Pernilla
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Association between marginal jawbone loss and the onset of rheumatoid arhtritis and relationship to plasma levels of RANKL2018Ingår i: Arthritis & Rheumatology, ISSN 2326-5191, E-ISSN 2326-5205, Vol. 70, nr 4, s. 508-515Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: To investigate whether periodontitis, characterized by marginal jawbone loss, precedes the onset of symptoms of rheumatoid arthritis (RA), and to analyze plasma levels of RANKL (a cytokine that is crucial for bone resorption) and anti–citrullinated peptide antibodies (ACPAs) in presymptomatic individuals compared with matched referent controls.

    Methods: Marginal jawbone loss was measured on dental radiographs of the premolar/molar regions in the jaws in 176 subjects, 93 of whom subsequently developed RA. Among these participating subjects, 46 had documented radiographs predating symptom onset, and 45 cases could be matched to controls, according to sex, age, and smoking status. Plasma RANKL concentrations were analyzed using enzyme‐linked immunosorbent assay. A receiver operating characteristic curve was used to define the cutoff value for RANKL positivity.

    Results: Bone loss was significantly greater in presymptomatic subjects classified as never smokers compared with that in controls, and increasing levels of bone loss were associated with a higher risk of the subsequent development of RA (hazard ratio 1.03, 95% confidence interval 1.01–1.05). No association between jawbone loss and RA was observed in smokers. A significantly greater extent of marginal jawbone loss was detected in RANKL‐positive presymptomatic subjects, and even more pronounced jawbone loss was observed in those who were positive for both RANKL and ACPA.

    Conclusion: Marginal jawbone loss preceded the clinical onset of RA symptoms, but this was observed only in nonsmokers. Moreover, marginal jawbone loss was significantly greater in RANKL‐positive presymptomatic subjects compared with RANKL‐negative presymptomatic subjects and was highest in presymptomatic subjects positive for both ACPA and RANKL.

  • 83. Koivula, R. W.
    et al.
    Grontved, A.
    Johansson, Ingegerd
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Wennberg, Patrik
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Ostergaard, L.
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Renstrom, Frida
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning. Department of Clinical Sciences, Lund University, Malmö, Sweden.
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Bicycling to work and primordial prevention of cardiovascular and type 2 diabetes risk: a cohort study from Northern Sweden2016Ingår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 59, s. S150-S150, artikel-id 298Artikel i tidskrift (Refereegranskat)
  • 84. Kuo, Chih-Hsi S.
    et al.
    Pavlidis, Stelios
    Zhu, Jie
    Loza, Matthew
    Baribaud, Fred
    Rowe, Anthony
    Pandis, Ioannis
    Gibeon, David
    Hoda, Uruj
    Sousa, Ana
    Wilson, Susan J.
    Howarth, Peter
    Shaw, Dominick
    Fowler, Stephen
    Dahlen, Barbro
    Chanez, Pascal
    Krug, Norbert
    Sandström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Fleming, Louise
    Corfield, Julie
    Auffray, Charles
    Djukanovic, Ratko
    Sterk, Peter J.
    Guo, Yike
    Adcock, Ian M.
    Chung, Kian Fan
    Contribution of airway eosinophils in airway wall remodeling in asthma: Role of MMP-10 and MET2019Ingår i: Allergy. European Journal of Allergy and Clinical Immunology, ISSN 0105-4538, E-ISSN 1398-9995, Vol. 74, nr 6, s. 1102-1112Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background Eosinophils play an important role in the pathophysiology of asthma being implicated in airway epithelial damage and airway wall remodeling. We determined the genes associated with airway remodeling and eosinophilic inflammation in patients with asthma. Methods We analyzed the transcriptomic data from bronchial biopsies of 81 patients with moderate-to-severe asthma of the U-BIOPRED cohort. Expression profiling was performed using Affymetrix arrays on total RNA. Transcription binding site analysis used the PRIMA algorithm. Localization of proteins was by immunohistochemistry. Results Using stringent false discovery rate analysis, MMP-10 and MET were significantly overexpressed in biopsies with high mucosal eosinophils (HE) compared to low mucosal eosinophil (LE) numbers. Immunohistochemical analysis confirmed increased expression of MMP-10 and MET in bronchial epithelial cells and in subepithelial inflammatory and resident cells in asthmatic biopsies. Using less-stringent conditions (raw P-value < 0.05, log2 fold change > 0.5), we defined a 73-gene set characteristic of the HE compared to the LE group. Thirty-three of 73 genes drove the pathway annotation that included extracellular matrix (ECM) organization, mast cell activation, CC-chemokine receptor binding, circulating immunoglobulin complex, serine protease inhibitors, and microtubule bundle formation pathways. Genes including MET and MMP10 involved in ECM organization correlated positively with submucosal thickness. Transcription factor binding site analysis identified two transcription factors, ETS-1 and SOX family proteins, that showed positive correlation with MMP10 and MET expression. Conclusion Pathways of airway remodeling and cellular inflammation are associated with submucosal eosinophilia. MET and MMP-10 likely play an important role in these processes.

  • 85. Lebedeva, A
    et al.
    Sundström, Anna
    Umeå universitet, Samhällsvetenskapliga fakulteten, Enheten för demografi och åldrandeforskning (CEDAR). Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Lindgren, Lenita
    Umeå universitet, Medicinska fakulteten, Institutionen för omvårdnad. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Stomby, A
    Stomby, Andreas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin. Jönköping County Hospital, Region Jönköping County, Jönköping, Sweden.
    Aarsland, D
    Westman, E
    Winblad, B
    Olsson, Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Longitudinal relationships among depressive symptoms, cortisol, and brain atrophy in the neocortex and the hippocampus2018Ingår i: Acta Psychiatrica Scandinavica, ISSN 0001-690X, E-ISSN 1600-0447, Vol. 167, nr 6, s. 491-502Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: Depression is associated with accelerated aging and age-related diseases. However, mechanisms underlying this relationship remain unclear. The aim of this study was to longitudinally assess the link between depressive symptoms, brain atrophy, and cortisol levels.

    METHOD: Participants from the Betula prospective cohort study (mean age = 59 years, SD = 13.4 years) underwent clinical, neuropsychological and brain 3T MRI assessments at baseline and a 4-year follow-up. Cortisol levels were measured at baseline in four saliva samples. Cortical and hippocampal atrophy rates were estimated and compared between participants with and without depressive symptoms (n = 81) and correlated with cortisol levels (n = 49).

    RESULTS: Atrophy in the left superior frontal gyrus and right lingual gyrus developed in parallel with depressive symptoms, and in the left temporal pole, superior temporal cortex, and supramarginal cortex after the onset of depressive symptom. Depression-related atrophy was significantly associated with elevated cortisol levels. Elevated cortisol levels were also associated with widespread prefrontal, parietal, lateral, and medial temporal atrophy.

    CONCLUSION: Depressive symptoms and elevated cortisol levels are associated with atrophy of the prefrontal and limbic areas of the brain.

  • 86. Lepzien, Rico
    et al.
    Rankin, Gregory
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Pourazar, Jamshid
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Muala, Ala
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Eklund, Anders
    Grunewald, Johan
    Blomberg, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Smed-Sorensen, Anna
    Mapping mononuclear phagocytes in blood, lungs, and lymph nodes of sarcoidosis patients2019Ingår i: Journal of Leukocyte Biology, ISSN 0741-5400, E-ISSN 1938-3673, Vol. 105, nr 4, s. 797-807Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Sarcoidosis is a T-cell driven inflammatory disease characterized by granuloma formation. Mononuclear phagocytes (MNPs)-macrophages, monocytes, and dendritic cells (DCs)-are likely critical in sarcoidosis as they initiate and maintain T cell activation and contribute to granuloma formation by cytokine production. Granulomas manifest primarily in lungs and lung-draining lymph nodes (LLNs) but these compartments are less studied compared to blood and bronchoalveolar lavage (BAL). Sarcoidosis can present with an acute onset (usually Lofgren's syndrome (LS)) or a gradual onset (non-LS). LS patients typically recover within 2 years while 60% of non-LS patients maintain granulomas for up to 5 years. Here, four LS and seven non-LS patients underwent bronchoscopy with endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). From each patient, blood, BAL, endobronchial biopsies (EBBs), and LLN samples obtained by EBUS-TBNA were collected and MNPs characterized using multicolor flow cytometry. Six MNP subsets were identified at varying frequencies in the anatomical compartments investigated. Importantly, monocytes and DCs were most mature with migratory potential in BAL and EBBs but not in the LLNs suggesting heterogeneity in MNPs in the compartments typically affected in sarcoidosis. Additionally, in LS patients, frequencies of DC subsets were lower or lacking in LLNs and EBBs, respectively, compared to non-LS patients that may be related to the disease outcome. Our work provides a foundation for future investigations of MNPs in sarcoidosis to identify immune profiles of patients at risk of developing severe disease with the aim to provide early treatment to slow down disease progression.

  • 87. Lindholm, Daniel
    et al.
    James, Stefan
    Andersson, Jonas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Braun, Oscar O.
    Heller, Susanne
    Henriksson, Peter
    Lauermann, Jorg
    Ohagen, Patrik
    Varenhorst, Christoph
    Caffeine and incidence of dyspnea in patients treated with ticagrelor2018Ingår i: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 200, s. 141-143Artikel i tidskrift (Refereegranskat)
  • 88. Linné, Anneli
    et al.
    Forsberg, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin. Department of Surgery, Sunderby Hospital, Luleå, Sweden.
    Lindström, David
    Ideskog, Ester
    Hultgren, Rebecka
    Age at detection of abdominal aortic aneurysms in siblings of patients with abdominal aortic aneurysms2016Ingår i: Journal of Vascular Surgery, ISSN 0741-5214, E-ISSN 1097-6809, Vol. 63, nr 4, s. 883-887Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: Few countries offer organized screening of siblings of patients with abdominal aortic aneurysms (AAAs), although a hereditary trait is well known to exist. Male relatives, but not female, are invited within the population-based screening programs for elderly men in Sweden. Evidence regarding the optimal age to screen siblings is scarce. The aim of this study was to describe the age at detection in siblings found with AAAs. Methods: All patients treated for AAAs in two Swedish counties were screened for siblings. Consenting siblings aged 80 and younger were examined (N = 529) with ultrasound and were interviewed per protocol. Results: In the cohort of 529 siblings to AAA patients, 53 siblings were diagnosed with AAAs (sisters 16/276 [5.8%] and brothers 37/253 [14.6%]). The prevalence of AAAs in the siblings 65 years of age or younger was 16/207 (7.7%). One-third of the siblings found with AAAs were young (16/53 [30%]). Among the young siblings with AAAs, 8/16 (50%) had an aneurysm larger than 50 mm or were already surgically treated. The prevalence of AAAs in siblings older than 65 years of age was 37/322 (12%). Conclusions: The AAA prevalence in this sibling cohort is strikingly high compared to the prevalence in the population (in Sweden, 1.4%-2.2% in 65-year-old men). The young ages among diagnosed siblings reinforce that male siblings of AAA patients should be screened before age 65 (before the population-based program) and that structured programs for female siblings are called for.

  • 89. Lundström, Erik
    et al.
    Isaksson, Eva
    Wester, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin. Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.
    Laska, Ann-Charlotte
    Näsman, Per
    Enhancing Recruitment Using Teleconference and Commitment Contract (ERUTECC): study protocol for a randomised, stepped-wedge cluster trial within the EFFECTS trial2018Ingår i: Trials, ISSN 1745-6215, E-ISSN 1745-6215, Vol. 19, artikel-id 14Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Many randomised controlled trials (RCTs) fail to meet their recruitment goals in time. Trialists are advised to include study recruitment strategies within their trials. EFFECTS is a Swedish, academic-led RCT of fluoxetine for stroke recovery. The trial's primary objective is to investigate whether 20 mg fluoxetine daily compared with placebo for 6 months after an acute stroke improves the patient's functional outcome. The first patient was included on 20 October 2014 and, as of 31 August 2017, EFFECTS has included 810 of planned 1500 individuals. EFFECTS currently has 32 active centres. The primary objective of the ERUTECC (Enhancing Recruitment Using Teleconference and Commitment Contract) study is to investigate whether a structured teleconference re-visit with the study personnel at the centres, accompanied by a commitment contract, can enhance recruitment by 20% at 60 days post intervention, compared with 60 days pre-intervention, in an ongoing RCT.

    Methods: ERUTECC is a randomised, stepped-wedge cluster trial embedded in EFFECTS. The plan is to start ERUTECC with a running-in period of September 2017. The first intervention is due in October 2017, and the study will continue for 12 months. We are planning to intervene at all active centres in EFFECTS, except the five top recruiting centres (n=27). The rationale for not intervening at the top recruiting centres is that we believe they have reached their full potential and the intervention would be too weak for them. The hypothesis of this study is that a structured teleconference re-visit with the study personnel at the centres, accompanied by a commitment contract, can enhance recruitment by 20% 60 days post intervention, compared to 60 days pre-intervention, in an ongoing RCT.

    Discussion: EFFECTS is a large, pragmatic RCT of stroke in Sweden. Results from the embedded ERUTECC study could probably be generalised to high-income Western countries, and is relevant to trial management and could improve trial management in the future. It might also be useful in clinical settings outside the field of stroke.

  • 90.
    Lundström, Karl-Johan
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap.
    Holmberg, Henrik
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Montgomery, A.
    Nordin, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap.
    Patient-reported rates of chronic pain and recurrence after groin hernia repair2018Ingår i: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 105, nr 1, s. 106-112Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The effectiveness of different procedures in routine surgical practice for hernia repair with respect to chronic postoperative pain and reoperation rates is not clear.

    Methods: This was prospective cohort study based on a unique combination of patient-reported outcomes and national registry data. Virtually all patients with a groin hernia repair in Sweden between September 2012 and April 2015 were sent a questionnaire 1 year after surgery. Persistent pain, defined as at least "pain present, cannot be ignored, and interferes with concentration on everyday activities' in the past week was the primary outcome. Reoperation for recurrence recorded in the register was the secondary outcome.

    Results: In total, 22 917 patients (response rate 75.5 per cent) who had an elective unilateral groin hernia repair were analysed. Persistent pain present 1 year after hernia repair was reported by 15.2 per cent of patients. The risk was least for endoscopic total extraperitoneal (TEP) repair (adjusted odds ratio (OR) 0.84, 95 per cent c.i. 0.74 to 0.96), compared with open anterior mesh repair. TEP repair had an increased risk of reoperation for recurrence (adjusted OR 2.14, 1.52 to 2.98), as did open preperitoneal mesh repair (adjusted OR 2.34, 1.42 to 3.71) at 2.5-year follow-up. No other methods of repair differed significantly from open anterior mesh repair.

    Conclusion: The risk of significant pain 1year after groin hernia repair in routine surgical practice was 15.2 per cent. This figure was lower in patients who had surgery by an endoscopic technique, but at the price of a significantly higher risk of reoperation for recurrence.

  • 91.
    Magaard, Gustaf
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering. Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Wester, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin. Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.
    Levi, Richard
    Lindvall, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap.
    Gustafsson, Emma
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering.
    Nazemroaya Sedeh, Arzhang
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering.
    Lönnqvist, Malin
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering.
    Berggren, Stina
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering.
    Nyman, Kristin
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap.
    Hu, Xiao-Lei
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering. Neurocentrum, NUS.
    Identifying unmet rehabilitation needs in patients after stroke with a graphic rehab-compassTM2018Ingår i: Journal of Stroke & Cerebrovascular Diseases, ISSN 1052-3057, E-ISSN 1532-8511, Vol. 27, nr 11, s. 3224-3235Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Unmet rehabilitation needs are common among stroke survivors. We aimed to evaluate whether a comprehensive graphic "Rehab-Compass," a novel combination of structured patient-reported outcome measures, was feasible and useful in facilitating a capture of patients' rehabilitation needs in clinical practice.

    METHODS: A new graphic overview of broad unmet rehabilitation needs covers deficits in functioning, daily activity, participation, and quality of life. It was constructed by using 5 patient-oriented, well-validated, and reliable existing instruments with converted data into a 0 (worst outcome) to 100 (best outcome) scale but unchanged in terms of variable properties. Satisfaction of the Rehab-CompassTM was studied by a qualitative interview of 9 patients with stroke and 3 clinicians. Practical feasibility and capacity of the instrument were evaluated in a cross-sectionalstudy with 48 patients at 5-month follow-ups after subarachnoid hemorrhage.

    RESULTS: The Rehab-CompassTM identified and graphically visualized a panoramic view of the multidimensional needs over time which was completed before clinical consultation. The Rehab-CompassTM appeared to be feasible and time-efficientin clinical use. The interviews of both patients and clinicians showed high satisfaction when using the Rehab-CompassTM graph. In the studied stroke patients, the Rehab-CompassTM identified memory and processing information, fatigue, mood, and pain after subarachnoid hemorrhage as the most common problems.

    CONCLUSIONS: The graphic Rehab-CompassTM seems to be a feasible, useful, and time-saving tool for identification of unmet rehabilitation needs among stroke survivors in clinical practice. Further research is needed to make the Rehab-CompassTM more concise and evaluate the instrument among different stroke subgroups.

  • 92. Mahajan, Anubha
    et al.
    Wessel, Jennifer
    Willems, Sara M.
    Zhao, Wei
    Robertson, Neil R.
    Chu, Audrey Y.
    Gan, Wei
    Kitajima, Hidetoshi
    Taliun, Daniel
    Rayner, N. William
    Guo, Xiuqing
    Lu, Yingchang
    Li, Man
    Jensen, Richard A.
    Hu, Yao
    Huo, Shaofeng
    Lohman, Kurt K.
    Zhang, Weihua
    Cook, James P.
    Prins, Bram Peter
    Flannick, Jason
    Grarup, Niels
    Trubetskoy, Vassily Vladimirovich
    Kravic, Jasmina
    Kim, Young Jin
    Rybin, Denis V.
    Yaghootkar, Hanieh
    Mueller-Nurasyid, Martina
    Meidtner, Karina
    Li-Gao, Ruifang
    Varga, Tibor V.
    Marten, Jonathan
    Li, Jin
    Smith, Albert Vernon
    An, Ping
    Ligthart, Symen
    Gustafsson, Stefan
    Malerba, Giovanni
    Demirkan, Ayse
    Tajes, Juan Fernandez
    Steinthorsdottir, Valgerdur
    Wuttke, Matthias
    Lecoeur, Cecile
    Preuss, Michael
    Bielak, Lawrence F.
    Graff, Marielisa
    Highland, Heather M.
    Justice, Anne E.
    Liu, Dajiang J.
    Marouli, Eirini
    Peloso, Gina Marie
    Warren, Helen R.
    Afaq, Saima
    Afzal, Shoaib
    Ahlqvist, Emma
    Almgren, Peter
    Amin, Najaf
    Bang, Lia B.
    Bertoni, Alain G.
    Bombieri, Cristina
    Bork-Jensen, Jette
    Brandslund, Ivan
    Brody, Jennifer A.
    Burtt, Noel P.
    Canouil, Mickael
    Chen, Yii-Der Ida
    Cho, Yoon Shin
    Christensen, Cramer
    Eastwood, Sophie V.
    Eckardt, Kai-Uwe
    Fischer, Krista
    Gambaro, Giovanni
    Giedraitis, Vilmantas
    Grove, Megan L.
    de Haan, Hugoline G.
    Hackinger, Sophie
    Hai, Yang
    Han, Sohee
    Tybjaerg-Hansen, Anne
    Hivert, Marie-France
    Isomaa, Bo
    Jager, Susanne
    Jorgensen, Marit E.
    Jorgensen, Torben
    Karajamaki, Annemari
    Kim, Bong-Jo
    Kim, Sung Soo
    Koistinen, Heikki A.
    Kovacs, Peter
    Kriebel, Jennifer
    Kronenberg, Florian
    Lall, Kristi
    Lange, Leslie A.
    Lee, Jung-Jin
    Lehne, Benjamin
    Li, Huaixing
    Lin, Keng-Hung
    Linneberg, Allan
    Liu, Ching-Ti
    Liu, Jun
    Loh, Marie
    Magi, Reedik
    Mamakou, Vasiliki
    McKean-Cowdin, Roberta
    Nadkarni, Girish
    Neville, Matt
    Nielsen, Sune F.
    Ntalla, Ioanna
    Peyser, Patricia A.
    Rathmann, Wolfgang
    Rice, Kenneth
    Rich, Stephen S.
    Rode, Line
    Rolandsson, Olov
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Schonherr, Sebastian
    Selvin, Elizabeth
    Small, Kerrin S.
    Stancakova, Alena
    Surendran, Praveen
    Taylor, Kent D.
    Teslovich, Tanya M.
    Thorand, Barbara
    Thorleifsson, Gudmar
    Tin, Adrienne
    Tonjes, Anke
    Varbo, Anette
    Witte, Daniel R.
    Wood, Andrew R.
    Yajnik, Pranav
    Yao, Jie
    Yengo, Loic
    Young, Robin
    Amouyel, Philippe
    Boeing, Heiner
    Boerwinkle, Eric
    Bottinger, Erwin P.
    Chowdhury, Rajiv
    Collins, Francis S.
    Dedoussis, George
    Dehghan, Abbas
    Deloukas, Panos
    Ferrario, Marco M.
    Ferrieres, Jean
    Florez, Jose C.
    Frossard, Philippe
    Gudnason, Vilmundur
    Harris, Tamara B.
    Heckbert, Susan R.
    Howson, Joanna M. M.
    Ingelsson, Martin
    Kathiresan, Sekar
    Kee, Frank
    Kuusisto, Johanna
    Langenberg, Claudia
    Launer, Lenore J.
    Lindgren, Cecilia M.
    Mannisto, Satu
    Meitinger, Thomas
    Melander, Olle
    Mohlke, Karen L.
    Moitry, Marie
    Morris, Andrew D.
    Murray, Alison D.
    de Mutsert, Renee
    Orho-Melander, Marju
    Owen, Katharine R.
    Perola, Markus
    Peters, Annette
    Province, Michael A.
    Rasheed, Asif
    Ridker, Paul M.
    Rivadineira, Fernando
    Rosendaal, Frits R.
    Rosengren, Anders H.
    Salomaa, Veikko
    Sheu, Wayne H. -H.
    Sladek, Rob
    Smith, Blair H.
    Strauch, Konstantin
    Uitterlinden, Andre G.
    Varma, Rohit
    Willer, Cristen J.
    Bluher, Matthias
    Butterworth, Adam S.
    Chambers, John Campbell
    Chasman, Daniel I.
    Danesh, John
    van Duijn, Cornelia
    Dupuis, Josee
    Franco, Oscar H.
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Froguel, Philippe
    Grallert, Harald
    Groop, Leif
    Han, Bok-Ghee
    Hansen, Torben
    Hattersley, Andrew T.
    Hayward, Caroline
    Ingelsson, Erik
    Kardia, Sharon L. R.
    Karpe, Fredrik
    Kooner, Jaspal Singh
    Kottgen, Anna
    Kuulasmaa, Kari
    Laakso, Markku
    Lin, Xu
    Lind, Lars
    Liu, Yongmei
    Loos, Ruth J. F.
    Marchini, Jonathan
    Metspalu, Andres
    Mook-Kanamori, Dennis
    Nordestgaard, Borge G.
    Palmer, Colin N. A.
    Pankow, James S.
    Pedersen, Oluf
    Psaty, Bruce M.
    Rauramaa, Rainer
    Sattar, Naveed
    Schulze, Matthias B.
    Soranzo, Nicole
    Spector, Timothy D.
    Stefansson, Kari
    Stumvoll, Michael
    Thorsteinsdottir, Unnur
    Tuomi, Tiinamaija
    Tuomilehto, Jaakko
    Wareham, Nicholas J.
    Wilson, James G.
    Zeggini, Eleftheria
    Scott, Robert A.
    Barroso, Ines
    Frayling, Timothy M.
    Goodarzi, Mark O.
    Meigs, James B.
    Boehnke, Michael
    Saleheen, Danish
    Morris, Andrew P.
    Rotter, Jerome I.
    McCarthy, Mark I.
    Refining the accuracy of validated target identification through coding variant fine-mapping in type 2 diabetes2018Ingår i: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 50, nr 4, s. 559-571Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We aggregated coding variant data for 81,412 type 2 diabetes cases and 370,832 controls of diverse ancestry, identifying 40 coding variant association signals (P < 2.2 × 10−7); of these, 16 map outside known risk-associated loci. We make two important observations. First, only five of these signals are driven by low-frequency variants: even for these, effect sizes are modest (odds ratio ≤1.29). Second, when we used large-scale genome-wide association data to fine-map the associated variants in their regional context, accounting for the global enrichment of complex trait associations in coding sequence, compelling evidence for coding variant causality was obtained for only 16 signals. At 13 others, the associated coding variants clearly represent ‘false leads’ with potential to generate erroneous mechanistic inference. Coding variant associations offer a direct route to biological insight for complex diseases and identification of validated therapeutic targets; however, appropriate mechanistic inference requires careful specification of their causal contribution to disease predisposition.

  • 93. Majeed, Ammar
    et al.
    Wallvik, Niklas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Eriksson, Joakim
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Höijer, Jonas
    Bottai, Matteo
    Holmström, Margareta
    Schulman, Sam
    Optimal timing of vitamin K antagonist resumption after upper gastrointestinal bleeding2017Ingår i: Thrombosis and Haemostasis, ISSN 0340-6245, Vol. 117, nr 3, s. 491-499Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The optimal timing of vitamin K antagonists (VKAs) resumption after an upper gastrointestinal (GI) bleeding, in patients with continued indication for oral anticoagulation, is uncertain. We included consecutive cases of VKA-associated upper GI bleeding from three hospitals retrospectively. Data on the bleeding location, timing of VKA resumption, recurrent GI bleeding and thromboembolic events were collected. A model was constructed to evaluate the 'total risk', based on the sum of the cumulative rates of recurrent GI bleeding and thromboembolic events, depending on the timing of VKA resumption. A total of 121 (58%) of 207 patients with VKA-associated upper GI bleeding were restarted on anticoagulation after a median (interquartile range) of one (0.2-3.4) week after the index bleeding. Restarting VKAs was associated with a reduced risk of thromboembolism (HR 0.19; 95 % CI, 0.07-0.55) and death (HR 0.61; 95% CI, 0.39-0.94), but with an increased risk of recurrent GI bleeding (HR 2.5; 95% CI, 1.4-4.5). The composite risk obtained from the combined statistical model of recurrent GI bleeding, and thromboembolism decreased if VKAs were resumed after three weeks and reached a nadir at six weeks after the index GI bleeding. On this background we will discuss how the disutility of the outcomes may influence the decision regarding timing of resumption. In conclusion, the optimal timing of VKA resumption after VKA-associated upper GI bleeding appears to be between 3-6 weeks after the index bleeding event but has to take into account the degree of thromboembolic risk, patient values and preferences.

  • 94. Manousou, S.
    et al.
    Stål, M.
    Larsson, Christel
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för kostvetenskap. Department of Food and Nutrition, and Sport Science, University of Gothenburg, Göteborg, Sweden.
    Mellberg, Caroline
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Lindahl, Bernt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Eggertsen, R.
    Hulthén, L.
    Olsson, Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Ryberg, Mats
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Sandberg, Susanne
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Nyström, H. F.
    A Paleolithic-type diet results in iodine deficiency: a 2-year randomized trial in postmenopausal obese women.2018Ingår i: European Journal of Clinical Nutrition, ISSN 0954-3007, E-ISSN 1476-5640, Vol. 72, nr 1, s. 124-129Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND/OBJECTIVES: Different diets are used for weight loss. A Paleolithic-type diet (PD) has beneficial metabolic effects, but two of the largest iodine sources, table salt and dairy products, are excluded. The objectives of this study were to compare 24-h urinary iodine concentration (24-UIC) in subjects on PD with 24-UIC in subjects on a diet according to the Nordic Nutrition Recommendations (NNR) and to study if PD results in a higher risk of developing iodine deficiency (ID), than NNR diet.

    SUBJECTS/METHODS: A 2-year prospective randomized trial in a tertiary referral center where healthy postmenopausal overweight or obese women were randomized to either PD (n=35) or NNR diet (n=35). Dietary iodine intake, 24-UIC, 24-h urinary iodine excretion (24-UIE), free thyroxin (FT4), free triiodothyronine (FT3) and thyrotropin (TSH) were measured at baseline, 6 and 24 months. Completeness of urine sampling was monitored by para-aminobenzoic acid and salt intake by urinary sodium.

    RESULTS: At baseline, median 24-UIC (71.0 μg/l) and 24-UIE (134.0 μg/d) were similar in the PD and NNR groups. After 6 months, 24-UIC had decreased to 36.0 μg/l (P=0.001) and 24-UIE to 77.0 μg/d (P=0.001) in the PD group; in the NNR group, levels were unaltered. FT4, TSH and FT3 were similar in both groups, except for FT3 at 6 months being lower in PD than in NNR group.

    CONCLUSIONS: A PD results in a higher risk of developing ID, than a diet according to the NNR. Therefore, we suggest iodine supplementation should be considered when on a PD.

  • 95. Markgren, Rickard
    et al.
    Brännström, Margareta
    Umeå universitet, Medicinska fakulteten, Institutionen för omvårdnad.
    Lundgren, Claes
    Boman, Kurt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Impacts of person-centred integrated chronic heart failure and palliative home care on pharmacological heart failure treatment: a substudy of a randomised trial2019Ingår i: BMJ Supportive & Palliative Care, ISSN 2045-435X, E-ISSN 2045-4368, Vol. 9, nr 1, artikel-id e10Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: Patients with chronic heart failure (CHF) may be insufficiently treated pharmacologically. Recently, we presented a person-centred integrated Palliative advanced homecaRE and heart FailurE caRe (PREFER) strategy and compared it with usual care (control). Patients managed according to PREFER had improved health-related quality of life and markedly reduced hospitalisations compared with the control group. We hypothesised that these improvements may have been partly due to better drug treatments within the PREFER strategy. Thus, our aim in this study was to explore the management of drug treatments in the PREFER group compared with the control group.

    METHODS: Doses and numbers of drugs and the number of patients receiving the target doses based on current guidelines were measured and compared between the groups at the start and finish of the study.

    RESULTS: The percentages of ACE inhibitors (ACEIs) or mineralocorticoid receptor antagonists (MRAs) increased, while loop diuretics decreased in the PREFER arm during the study, although the differences were not significant. Beta-receptor blockers (BBs) decreased somewhat in both groups. The number of patients treated with MRAs differed the most between groups, and increased from 10 (28%) to 15 (48%) in the PREFER arm compared with 13 (35%) vs 13 (39%) in the control group. The change in patients receiving full target doses (+8 vs. +1) of the ACEIs/angiotensin receptor blockers, BBs and MRAs were significantly higher (p=0009) in the PREFER arm than in the control arm.

    CONCLUSIONS: Person-centred integrated care of patients with severe CHF was associated with increased evidence-based drug treatments, especially MRAs.

    CLINICAL TRIAL NUMBER: NCT01304381.

  • 96. Massad, Eduardo
    et al.
    Bezerra Coutinhol, Francisco Antonio
    Wilder-Smith, Annelies
    Umeå universitet, Medicinska fakulteten, Institutionen för epidemiologi och global hälsa. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Modelling an optimum vaccination strategy against ZIKA virus for outbreak use2019Ingår i: Epidemiology and Infection, ISSN 0950-2688, E-ISSN 1469-4409, Vol. 147, artikel-id UNSP e196Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We present a model to optimise a vaccination campaign aiming to prevent or to curb a Zika virus outbreak. We show that the optimum vaccination strategy to reduce the number of cases by a mass vaccination campaign should start when the Aedes mosquitoes' density reaches the threshold of 1.5 mosquitoes per humans, the moment the reproduction number crosses one. The maximum time it is advisable to wait for the introduction of a vaccination campaign is when the first ZIKV case is identified, although this would not be as effective to minimise the number of infections as when the mosquitoes' density crosses the critical threshold. This suboptimum strategy, however, would still curb the outbreak. In both cases, the catch up strategy should aim to vaccinate at least 25% of the target population during a concentrated effort of 1 month immediately after identifying the threshold. This is the time taken to accumulate the herd immunity threshold of 56.5%. These calculations were done based on theoretical assumptions that vaccine implementation would be feasible within a very short time frame.

  • 97. Meidtner, Karina
    et al.
    Podmore, Clara
    Kroger, Janine
    van der Schouw, Yvonne T.
    Bendinelli, Benedetta
    Agnoli, Claudia
    Arriola, Larraitz
    Barricarte, Aurelio
    Boeing, Heiner
    Cross, Amanda J.
    Dow, Courtney
    Ekblom, Kim
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Fagherazzi, Guy
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin. Department of Clinical Sciences, Lund University, Malmö, Sweden.
    Gunter, Marc J.
    Huerta, Jose Maria
    Jakszyn, Paula
    Jenab, Mazda
    Katzke, Verena A.
    Key, Timothy J.
    Khaw, Kay Tee
    Kuhn, Tilman
    Kyro, Cecilie
    Mancini, Francesca Romana
    Melander, Olle
    Nilsson, Peter M.
    Overvad, Kim
    Palli, Domenico
    Panico, Salvatore
    Quiros, J. Ramon
    Rodriguez-Barranco, Miguel
    Sacerdote, Carlotta
    Sluijs, Ivonne
    Stepien, Magdalena
    Tjonneland, Anne
    Tumino, Rosario
    Forouhi, Nita G.
    Sharp, Stephen J.
    Langenberg, Claudia
    Schulze, Matthias B.
    Riboli, Elio
    Wareham, Nicholas J.
    Interaction of Dietary and Genetic Factors Influencing Body Iron Status and Risk of Type 2 Diabetes Within the EPIC-InterAct Study2018Ingår i: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 41, nr 2, s. 277-285Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: Meat intake has been consistently shown to be positively associated with incident type 2 diabetes. Part of that association may be mediated by body iron status, which is influenced by genetic factors. We aimed to test for interactions of genetic and dietary factors influencing body iron status in relation to the risk of incident type 2 diabetes.

    RESEARCH DESIGN AND METHODS: The case-cohort comprised 9,347 case subjects and 12,301 subcohort participants from eight European countries. Single nucleotide polymorphisms (SNPs) were selected from genome-wide association studies on iron status biomarkers and candidate gene studies. A ferritin-related gene score was constructed. Multiplicative and additive interactions of heme iron and SNPs as well as the gene score were evaluated using Cox proportional hazards regression.

    RESULTS: Higher heme iron intake (per 1 SD) was associated with higher ferritin levels (β = 0.113 [95% CI 0.082; 0.144]), but not with transferrin (−0.019 [−0.043; 0.006]) or transferrin saturation (0.016 [−0.006; 0.037]). Five SNPs located in four genes (rs1799945 [HFE H63D], rs1800562 [HFE C282Y], rs236918 [PCK7], rs744653 [SLC40A1], and rs855791 [TMPRSS6V736A]) were associated with ferritin. We did not detect an interaction of heme iron and the gene score on the risk of diabetes in the overall study population (Padd = 0.16, Pmult = 0.21) but did detect a trend toward a negative interaction in men (Padd = 0.04, Pmult = 0.03).

    CONCLUSIONS: We found no convincing evidence that the interplay of dietary and genetic factors related to body iron status associates with type 2 diabetes risk above the level expected from the sum or product of the two individual exposures.

  • 98. Mitchell, Ulrike H
    et al.
    Hilton, Sterling C
    Hunsaker, Erik
    Ulfberg, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Decreased Symptoms without Augmented Skin Blood Flow in Subjects with RLS/WED after Vibration Treatment2016Ingår i: Journal of Clinical Sleep Medicine (JCSM), ISSN 1550-9389, E-ISSN 1550-9397, Vol. 12, nr 7, s. 947-952Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Study Objectives: Vascular disturbances leading to tissue hypoxia have been named as a possible cause for RLS/WED. Vibration to the whole body (WBV) in subjects with RLS/WED results in increased skin blood flow (SBF). The aims of this investigation were to (1) determine if a two-week treatment with WBV will decrease symptoms associated with RLS/WED and, (2) if so, determine if the mechanism for improvement in symptoms is related to an increase in SBF, as measured in flux. Methods: Eleven subjects with RLS/WED underwent 2 weeks of 14-minute intermittent WBV and a 2-week sham treatment in randomized order. Pre and post intervention RLS symptom severity were compared. Baseline SBF was compared between subjects with RLS/WED and an age-and sex-matched control group. A crossover design (aim 1) and a matched case-control design and repeated measures design (aim 2) were used. The data analyses consisted of 2-sample and paired t-tests; where applicable we used a standard crossover design adjustment. Results: WBV did significantly decrease symptoms associated with RLS/WED compared to baseline data and compared to sham treatment. The baseline flux was significantly lower in RLS/WED subjects than matched controls, but this deficit was negated with WBV. There was no increase in resting SBF over the 2 weeks of treatment. Conclusions: Subjects with RLS/WED have decreased SBF but are able to increase flux to the same level as normal subjects with WBV. A 2-week intervention with WBV decreases symptoms associated with RLS/WED, but this does not seem to be related to an increase in resting SBF.

  • 99.
    Nicoll, Rachel
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Environmental contaminants and congenital heart defects: a re-evaluation of the evidence2018Ingår i: International Journal of Environmental Research and Public Health, ISSN 1661-7827, E-ISSN 1660-4601, Vol. 15, nr 10, artikel-id 2096Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Congenital heart defects (CHDs) are a common birth defect of largely unknown etiology, with high fetal and neonatal mortality. A review of CHDs and environmental contaminant exposure found that meta-analyses showed only modest associations for smoking, vehicle exhaust components, disinfectant by-products and proximity to incinerators, with stronger results from the newer, larger and better quality studies masked by the typical absence of effect in older studies. Recent studies of exposure to agricultural pesticides, solvents, metals and landfill sites also showed associations. Certain contaminants have been associated with certain CHDs, with septal defects being the most common. Frequent methodological problems include failure to account for potential confounders or maternal/paternal preconception exposure, differences in diagnosing, defining and classifying CHDs, grouping of defects to increase power, grouping of contaminants with dissimilar mechanisms, exclusion of pregnancies that result in death or later life diagnosis, and the assumption that maternal residence at birth is the same as at conception. Furthermore, most studies use measurement estimates of one exposure, ignoring the many additional contaminant exposures in daily life. All these problems can distort and underestimate the true associations. Impaired methylation is a common mechanism, suggesting that supplementary folate may be protective for any birth defect.

  • 100.
    Nicoll, Rachel
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Henein, Michael Y.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Caloric Restriction and Its Effect on Blood Pressure, Heart Rate Variability and Arterial Stiffness and Dilatation: A Review of the Evidence2018Ingår i: International Journal of Molecular Sciences, ISSN 1422-0067, E-ISSN 1422-0067, Vol. 19, nr 3, artikel-id 751Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Essential hypertension, fast heart rate, low heart rate variability, sympathetic nervous system dominance over parasympathetic, arterial stiffness, endothelial dysfunction and poor flow-mediated arterial dilatation are all associated with cardiovascular mortality and morbidity. This review of randomised controlled trials and other studies demonstrates that caloric restriction (CR) is capable of significantly improving all these parameters, normalising blood pressure (BP) and allowing patients to discontinue antihypertensive medication, while never becoming hypotensive. CR appears to be effective regardless of age, gender, ethnicity, weight, body mass index (BMI) or a diagnosis of metabolic syndrome or type 2 diabetes, but the greatest benefit is usually observed in the sickest subjects and BP may continue to improve during the refeeding period. Exercise enhances the effects of CR only in hypertensive subjects. There is as yet no consensus on the mechanism of effect of CR and it may be multifactorial. Several studies have suggested that improvement in BP is related to improvement in insulin sensitivity, as well as increased nitric oxide production through improved endothelial function. In addition, CR is known to induce SIRT1, a nutrient sensor, which is linked to a number of beneficial effects in the body.

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