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  • 1. Adlard, B.
    et al.
    Donaldson, S. G.
    Odland, J. O.
    Weihe, P.
    Berner, J.
    Carlsen, A.
    Bonefeld-Jorgensen, E. C.
    Dudarev, A. A.
    Gibson, J. C.
    Krümmel, E. M.
    Olafsdottir, K.
    Abass, K.
    Rautio, A.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Bergdahl, Ingvar A.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Mulvad, G.
    Future directions for monitoring and human health research for the Arctic Monitoring and Assessment Programme2018In: Global Health Action, ISSN 1654-9716, E-ISSN 1654-9880, Vol. 11, no 1, article id 1480084Article in journal (Refereed)
    Abstract [en]

    For the last two and a half decades, a network of human health experts under the Arctic Monitoring and Assessment Program (AMAP) has produced several human health assessment reports. These reports have provided a base of scientific knowledge regarding environmental contaminants and their impact on human health in the Arctic. These reports provide scientific information and policy-relevant recommendations to Arctic governments. They also support international agreements such as the Stockholm Convention on Persistent Organic Pollutants (POPs) and the Minamata Convention on Mercury. Key topics discussed in this paper regarding future human health research in the circumpolar Arctic are continued contaminant biomonitoring, health effects research and risk communication. The objective of this paper is to describe knowledge gaps and future priorities for these fields.

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  • 2. Ajroud-Driss, Senda
    et al.
    Adams, David
    Coelho, Teresa
    Polydefkis, Michael
    Gonzalez-Duarte, Alejandra
    Quan, Dianna
    Kristen, Arnt
    Berk, John L.
    Partisano, Angela M.
    Gollob, Jared
    Sweetser, Marianne T.
    Chen, Jihong
    Agarwal, Sonalee
    Suhr, Ole B.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Impact of Patisiran on Overall Health Status in hATTR Amyloidosis: Results from the APOLLO Trial2019In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 92, no 15Article in journal (Other academic)
  • 3. Allin, Kristine H.
    et al.
    Tremaroli, Valentina
    Caesar, Robert
    Jensen, Benjamin A. H.
    Damgaard, Mads T. F.
    Bahl, Martin I.
    Licht, Tine R.
    Hansen, Tue H.
    Nielsen, Trine
    Dantoft, Thomas M.
    Linneberg, Allan
    Jørgensen, Torben
    Vestergaard, Henrik
    Kristiansen, Karsten
    Franks, Paul W.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Hansen, Torben
    Bäckhed, Fredrik
    Pedersen, Oluf
    Aberrant intestinal microbiota in individuals with prediabetes2018In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 61, no 4, p. 810-820Article in journal (Refereed)
    Abstract [en]

    Aims/hypothesis: Individuals with type 2 diabetes have aberrant intestinal microbiota. However, recent studies suggest that metformin alters the composition and functional potential of gut microbiota, thereby interfering with the diabetes-related microbial signatures. We tested whether specific gut microbiota profiles are associated with prediabetes (defined as fasting plasma glucose of 6.1-7.0 mmol/l or HbA1c of 42-48 mmol/mol [6.0-6.5%]) and a range of clinical biomarkers of poor metabolic health.

    Methods: In the present case-control study, we analysed the gut microbiota of 134 Danish adults with prediabetes, overweight, insulin resistance, dyslipidaemia and low-grade inflammation and 134 age-and sex-matched individuals with normal glucose regulation.

    Results: We found that five bacterial genera and 36 operational taxonomic units (OTUs) were differentially abundant between individuals with prediabetes and those with normal glucose regulation. At the genus level, the abundance of Clostridium was decreased (mean log2 fold change -0.64 (SEM 0.23), p adj = 0.0497), whereas the abundances of Dorea, [Ruminococcus], Sutterella and Streptococcus were increased (mean log2 fold change 0.51 (SEM 0.12), p adj = 5 x 10-4; 0.51 (SEM 0.11), p adj = 1 x 10-4; 0.60 (SEM 0.21), p adj = 0.0497; and 0.92 (SEM0.21), p adj = 4 x 10-4, respectively). The two OTUs that differed the most were a member of the order Clostridiales (OTU 146564) and Akkermansia muciniphila, which both displayed lower abundance among individuals with prediabetes (mean log2 fold change -1.74 (SEM0.41), p adj = 2 x 10-3 and -1.65 (SEM0.34), p adj = 4 x 10-4, respectively). Faecal transfer from donors with prediabetes or screen-detected, drug-naive type 2 diabetes to germfree Swiss Webster or conventional C57BL/6 J mice did not induce impaired glucose regulation in recipient mice.

    Conclusions/interpretation: Collectively, our data show that individuals with prediabetes have aberrant intestinal microbiota characterised by a decreased abundance of the genus Clostridium and the mucin-degrading bacterium A. muciniphila. Our findings are comparable to observations in overt chronic diseases characterised by low-grade inflammation.

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  • 4.
    Anan, Intissar
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Bång, Joakim
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Lundgren, Hans-Erik
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Wixner, Jonas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Westermark, Per
    A case report of osteoarthritis associated with hereditary transthyretin amyloidosis ATTRV30M2019In: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 26, p. 29-30Article in journal (Refereed)
  • 5. Andersen, Vibeke
    et al.
    Chan, Simon
    Luben, Robert
    Khaw, Kay-Tee
    Olsen, Anja
    Tjonneland, Anne
    Kaaks, R.
    Grip, Olof
    Bergmann, M. M.
    Boeing, H.
    Hultdin, Johan
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Karling, Pontus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Overvad, Kim
    Oldenburg, Bas
    Opstelten, Jorrit
    Boutron-Ruault, Marie-Christine
    Carbonnel, Franck
    Racine, Antoine
    Key, Timothy
    Masala, Giovanna
    Palli, Domenico
    Tumino, R.
    Trichopoulou, A.
    Riboli, Elio
    Hart, Andrew
    Fibre intake and the development of inflammatory bowel disease: A European prospective multi-centre cohort study (EPIC-IBD)2018In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 12, no 2, p. 129-136Article in journal (Refereed)
    Abstract [en]

    Background and Aims: Population-based prospective cohort studies investigating fibre intake and development of inflammatory bowel disease are lacking. Our aim was to investigate the association between fibre intake and the development of Crohn's disease [CD] and ulcerative colitis [UC] in a large European population.

    Methods: In total, 401 326 participants, aged 20-80 years, were recruited in eight countries in Europe between 1991 and 1998. At baseline, fibre intake [total fibres, fibres from fruit, vegetables and cereals] was recorded using food frequency questionnaires. The cohort was monitored for the development of inflammatory bowel disease. Each case was matched with four controls and odds ratios [ORs] for the exposures were calculated using conditional logistic regression. Sensitivity analyses according to smoking status were computed.

    Results: In total, 104 and 221 participants developed incident CD and UC, respectively. For both CD and UC, there were no statistically significant associations with either quartiles, or trends across quartiles, for total fibre or any of the individual sources. The associations were not affected by adjusting for smoking and energy intake. Stratification according to smoking status showed null findings apart from an inverse association with cereal fibre and CD in non-smokers [Quartile 4 vs 1 OR = 0.12, 95% confidence interval = 0.02-0.75, p = 0.023, OR trend across quartiles = 0.50, 95% confidence interval = 0.29-0.86, p = 0.017].

    Conclusion: The results do not support the hypothesis that dietary fibre is involved in the aetiology of UC, although future work should investigate whether there may be a protective effect of specific types of fibre according to smoking status in CD.

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  • 6.
    Andersson, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Infektioner hos patienter med inflammatorisk tarmsjukdom - inverkan av immunomodulerare och tumörnekrosfaktor-hämmare2019Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 7. Antoniewicz, Lukasz
    et al.
    Brynedal, Amelie
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Hedman, Linnea
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine. Division of Nursing, Department of Health Science, Luleå University of Technology, Luleå, Sweden..
    Lundbäck, Magnus
    Bosson, Jenny A.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Acute Effects of Electronic Cigarette Inhalation on the Vasculature and the Conducting Airways2019In: Cardiovascular Toxicology, ISSN 1530-7905, E-ISSN 1559-0259, Vol. 19, no 5, p. 441-450Article in journal (Refereed)
    Abstract [en]

    The use of electronic cigarettes has increased exponentially since its introduction onto the global market in 2006. However, short- and long-term health effects remain largely unknown due to the novelty of this product. The present study examines the acute effects of e-cigarette aerosol inhalation, with and without nicotine, on vascular and pulmonary function in healthy volunteers. Seventeen healthy subjects inhaled electronic cigarette aerosol with and without nicotine on two separate occasions in a double-blinded crossover fashion. Blood pressure, heart rate, and arterial stiffness measured by pulse wave velocity and pulse wave analysis were assessed at baseline, and then at 0 h, 2 h, and 4 h following exposure. Dynamic spirometry and impulse oscillometry were measured following vascular assessments at these time points, as well as at 6 h following exposure. e-Cigarette aerosol with nicotine caused a significant increase in heart rate and arterial stiffness. Furthermore, e-cigarette aerosol-containing nicotine caused a sudden increase in flow resistance as measured by impulse oscillometry, indicating obstruction of the conducting airways. Both aerosols caused an increase in blood pressure. The present study indicates that inhaled e-cigarette aerosol with nicotine has an acute impact on vascular and pulmonary function. Thus, chronic usage may lead to long-term adverse health effects. Further investigation is warranted.

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  • 8.
    Antoniewicz, Lukasz
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine. Karolinska Institutet, Department of Clinical Sciences, Division of Internal Medicine, Danderyd Hospital, Stockholm, Sweden.
    Novo, Mirza
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Bosson, Jenny A.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Lundbäck, Magnus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Brief exposure to Swedish snus causes divergent vascular responses in healthy male and female volunteers2018In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, no 4, article id e0195493Article in journal (Refereed)
    Abstract [en]

    Introduction: The use of Swedish oral moist snuff, known as snus, has for a long time been limited to the Scandinavian countries. With declining cigarette sales in the western world, tobacco companies have looked to the development of alternative tobacco products. In 2006 snus products were launched in the US. Even though several studies have demonstrated negative health effects, snus is often depicted as harmless.

    The aim of the present study was to investigate acute vascular effects of snus as measured by arterial stiffness as well as blood pressure and heart rate.

    Methods: Two separate randomized double-blind crossover studies with the same study design were pooled for analysis. Twenty-nine healthy snus-users (17 females, 12 males) were included. Snus (Göteborgs Rapé) and tobacco free snus (Onico) were administered in a randomized order at two separate visits. Arterial stiffness, blood pressure and heart rate were measured at baseline as well as every five minutes for 40 minutes during exposure. Following snus removal, measurements continued for 30 minutes post exposure. Arterial stiffness was measured using pulse wave velocity (Vicorder) and pulse wave analysis (Sphygmocor).

    Results: Compared to placebo, snus significantly increased systolic and diastolic blood pressure as well as heart rate, however, only in females (p = 0.004, p = 0.006 and p<0.001 respectively). No changes were seen in arterial stiffness measurements in either gender.

    Conclusion: We observed an increase in blood pressure and heart rate only in females, but not in males due to snus usage as compared to placebo. This novel finding was surprising and needs to be further investigated considering most of the earlier studies have mainly focused on male snus users and the increasing usage of snus among females.

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  • 9.
    Arvidsson, Sandra
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology.
    Henein, Michael Y
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Wikström, Gerhard
    Suhr, Ole B.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Lindqvist, Per
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology.
    Right ventricular involvement in transthyretin amyloidosis2018In: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 25, no 3, p. 160-166Article in journal (Refereed)
    Abstract [en]

    Background: The extent of right ventricular (RV) involvement in transthyretin amyloidosis (ATTR) is unknown.

    Objectives: This study sought to establish the degree of RV involvement in ATTR amyloidosis, and compare findings with RV involvement in hypertrophic cardiomyopathy (HCM).

    Methods: Forty-two patients with ATTR amyloidosis and echocardiographic evidence of cardiac amyloidosis (cardiac ATTR), 19 ATTR patients with normal left ventricular (LV) wall thickness (non-cardiac ATTR), 25 patients with diagnosed HCM and 30 healthy controls were included in this study. Echocardiographic measurements for conventional parameters, as well as RV global and segmental strain, were recorded.

    Results: When comparing RV structure and function between cardiac ATTR amyloidosis and HCM patients, only segmental strain differed between the two groups. In cardiac ATTR amyloidosis, we found an RV apex-to-base strain gradient with highest deformation in the apex. This pattern was reversed in patients with HCM.

    Conclusions: RV involvement is common in cardiac ATTR patients. The present study also detected an RV apical sparing pattern in patients with ATTR cardiomyopathy, similar to what has previously been described for the left ventricle in these patients. This pattern was not seen in HCM patients. Further studies are needed to assess the clinical importance of these findings.

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  • 10. Ashar, Foram N.
    et al.
    Mitchell, Rebecca N.
    Albert, Christine M.
    Newton-Cheh, Christopher
    Brody, Jennifer A.
    Mueller-Nurasyid, Martina
    Moes, Anna
    Meitinger, Thomas
    Mak, Angel
    Huikuri, Heikki
    Junttila, M. Juhani
    Goyette, Philippe
    Pulit, Sara L.
    Pazoki, Raha
    Tanck, MichaelW.
    Blom, Marieke T.
    Zhao, XiaoQing
    Havulinna, Aki S.
    Jabbari, Reza
    Glinge, Charlotte
    Tragante, Vinicius
    Escher, Stefan A.
    Chakravarti, Aravinda
    Ehret, Georg
    Coresh, Josef
    Li, Man
    Prineas, Ronald J.
    Franco, Oscar H.
    Kwok, Pui-Yan
    Lumley, Thomas
    Dumas, Florence
    McKnight, Barbara
    Rotter, Jerome I.
    Lemaitre, Rozenn N.
    Heckbert, Susan R.
    O'Donnell, Christopher J.
    Hwang, Shih-Jen
    Tardif, Jean-Claude
    VanDenburgh, Martin
    Uitterlinden, Andre G.
    Hofman, Albert
    Stricker, Bruno H. C.
    de Bakker, Paul I. W.
    Franks, Paul W.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Jansson, Jan-Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Asselbergs, Folkert W.
    Halushka, Marc K.
    Maleszewski, Joseph J.
    Tfelt-Hansen, Jacob
    Engstrom, Thomas
    Salomaa, Veikko
    Virmani, Renu
    Kolodgie, Frank
    Wilde, Arthur A. M.
    Tan, Hanno L.
    Bezzina, Connie R.
    Eijgelsheim, Mark
    Rioux, John D.
    Jouven, Xavier
    Kääb, Stefan
    Psaty, Bruce M.
    Siscovick, David S.
    Arking, Dan E.
    Sotoodehnia, Nona
    A comprehensive evaluation of the genetic architecture of sudden cardiac arrest2018In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 39, no 44, p. 3961-+Article in journal (Refereed)
    Abstract [en]

    Aims: Sudden cardiac arrest (SCA) accounts for 10% of adult mortality in Western populations. We aim to identify potential loci associated with SCA and to identify risk factors causally associated with SCA.

    Methods and results: We carried out a large genome-wide association study (GWAS) for SCA (n = 3939 cases, 25 989 non-cases) to examine common variation genome-wide and in candidate arrhythmia genes. We also exploited Mendelian randomization (MR) methods using cross-trait multi-variant genetic risk score associations (GRSA) to assess causal relationships of 18 risk factors with SCA. No variants were associated with SCA at genome-wide significance, nor were common variants in candidate arrhythmia genes associated with SCA at nominal significance. Using cross-trait GRSA, we established genetic correlation between SCA and (i) coronary artery disease (CAD) and traditional CAD risk factors (blood pressure, lipids, and diabetes), (ii) height and BMI, and (iii) electrical instability traits (QT and atrial fibrillation), suggesting aetiologic roles for these traits in SCA risk.

    Conclusions: Our findings show that a comprehensive approach to the genetic architecture of SCA can shed light on the determinants of a complex life-threatening condition with multiple influencing factors in the general population. The results of this genetic analysis, both positive and negative findings, have implications for evaluating the genetic architecture of patients with a family history of SCA, and for efforts to prevent SCA in high-risk populations and the general community.

  • 11.
    Asplund, Kjell
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Lundström, Staffan
    Stegmayr, Birgitta
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    End of life after stroke: a nationwide study of 42,502 deaths occurring within a year after stroke2018In: European Stroke Journal, ISSN 2396-9873, E-ISSN 2396-9881, Vol. 3, no 1, p. 74-81Article in journal (Refereed)
    Abstract [en]

    Introduction: In the scientific literature, there is very limited empirical information on end-of-life issues after stroke in the scientific literature. The present nationwide study describes the circumstances surrounding deaths that occur within a year after a stroke. Patients and methods: Datasets from three nationwide Swedish registers (on stroke, palliative care and cause of death) were linked. Basic information was available for 42,502 unselected cases of death that occurred within a year after a stroke and more detailed information was available for 16,408 deaths. Odds ratios for characteristics of end-of-life care were calculated by logistic regression. Results: In the late phase after stroke (three months to one year), 46% of patients died in a nursing home, whereas 37% of patients died in a hospital after readmission and 10% of patients died at home. Eleven per cent of deaths were reported as being unexpected. A next of kin was present at 49% of deaths. The frequency of unattended deaths (neither next of kin nor staff were present at the time of death) ranged from 5% at home with specialised home care to 25% in hospitals. Discussion: This is, by far, the largest study published on end-of-life issues after stroke. Major differences between countries in healthcare, community services, family structure and culture may limit direct transfer of the present results to other settings. Conclusion: There is considerable discordance between presumed good death' late after stroke (dying at home surrounded by family members) and the actual circumstances at the end of life.

  • 12.
    Awad, Anna
    et al.
    Department of Public Health and Clinical Medicine, Sunderby Research Unit, Umeå University, Sweden..
    Lundqvist, Robert
    Research and Innovation Unit, Norrbotten County Council, Luleå, Sweden..
    Rolandsson, Olov
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Sundström, Anna
    Umeå University, Faculty of Social Sciences, Department of Psychology. Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR).
    Eliasson, Mats
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine. Department of Public Health and Clinical Medicine, Sunderby Research Unit, Umeå University, Sweden..
    Lower cognitive performance among long-term type 1 diabetes survivors: A case-control study2017In: Journal of diabetes and its complications, ISSN 1056-8727, E-ISSN 1873-460X, Vol. 31, no 8, p. 1328-1331Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Patients with type 1 diabetes (T1D) have an increased risk of cognitive dysfunction. The cognitive decrement is believed to depend on macro- and microvascular complications and long disease duration. Some patients do not develop these complications, but still report cognitive symptoms. We examined if long-standing T1D without complications is associated with lower cognitive performance.

    METHODS: A group of patients (n=43) with long-standing T1D (>30years) without micro- or macro vascular complications was compared with a non-diabetic control group (n=86) on six cognitive tests which probed episodic memory, semantic memory, episodic short-term memory, visual attention and psychomotor speed. Each patient was matched with two controls regarding age, gender and education. A linear mixed effect model was used to analyze the data.

    RESULTS: The mean age was 57years and mean duration was 41years. Patients with diabetes had lower diastolic blood pressure but BMI, waist circumference, systolic blood pressure and smoking did not differ between groups. Patients had lower results than non-diabetic controls in episodic short-term memory (p<0.001) and also lower values on a test that mirrors visual attention and psychomotor speed (p=0.019).

    CONCLUSIONS: Long-standing T1D was associated with lower cognitive performance, regardless of other diabetes-related complications.

  • 13.
    Backman, Helena
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health.
    Jansson, Sven-Arne
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health.
    Stridsman, Caroline
    Department of Health Sciences, Luleå University of Technology, Luleå, Sweden..
    Eriksson, Berne
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Hedman, Linnea
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health.
    Eklund, Britt-Marie
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health.
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Lindberg, Anne
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Lundbäck, Bo
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health. Krefting Research Centre, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
    Rönmark, Eva
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health.
    Severe asthma: A population study perspective2019In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 49, no 6, p. 819-828Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Severe asthma is a considerable challenge for patients, health care professionals and society. Few studies have estimated the prevalence of severe asthma according to modern definitions of which none based on a population study.

    OBJECTIVE: To describe characteristics and estimate the prevalence of severe asthma in a large adult population-based asthma cohort followed for 10-28 years.

    METHODS: N=1006 subjects with asthma participated in a follow-up during 2012-14, when 830 (mean age 59y, 56% women) still had current asthma. Severe asthma was defined according to three internationally well-known criteria: the ATS workshop definition from 2000 used in the US Severe Asthma Research Program (SARP), the 2014 ATS/ERS Task force definition and the GINA 2017. All subjects with severe asthma according to any of these criteria were undergoing respiratory specialist care, and were also contacted by telephone to verify treatment adherence.

    RESULTS: The prevalence of severe asthma according to the three definitions was 3.6% (US SARP), 4.8% (ERS/ATS Taskforce), and 6.1% (GINA) among subjects with current asthma. Although all were using high ICS doses and other maintenance treatment, >40% had uncontrolled asthma according to the asthma control test. Severe asthma was related to age >50 years, nasal polyposis, impaired lung function, sensitization to aspergillus, and tended to be more common in women. Further, neutrophils in blood significantly discriminated severe asthma from other asthma.

    CONCLUSIONS AND CLINICAL RELEVANCE: Severe asthma differed significantly from other asthma in terms of demographic, clinical and inflammatory characteristics, results suggesting possibilities for improved treatment regimens of severe asthma. The prevalence of severe asthma in this asthma cohort was 4-6%, corresponding to approximately 0.5% of the general population.

  • 14.
    Backman, Helena
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine. Dept of Health Sciences, Luleå University of Technology, Luleå, Sweden..
    Lindberg, Anne
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Hedman, Linnea
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health. Dept of Health Sciences, Luleå University of Technology, Luleå, Sweden..
    Stridsman, Caroline
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine. Dept of Health Sciences, Luleå University of Technology, Luleå, Sweden..
    Jansson, Sven-Arne
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health.
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Lundbäck, Bo
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health.
    Rönmark, Eva
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health.
    FEV1 decline in relation to blood eosinophils and neutrophils in a population-based asthma cohort2020In: The World Allergy Organization journal, ISSN 1939-4551, Vol. 13, no 3, article id 100110Article in journal (Refereed)
    Abstract [en]

    Background: The relationship between lung function decline and eosinophils and neutrophils has important therapeutic implications among asthmatics, but it has rarely been studied in large cohort studies.

    Objective: The aim is to study the relationship between blood eosinophils and neutrophils and FEV1 decline in a long-term follow-up of a population-based adult asthma cohort.

    Methods: In 2012-2014, an adult asthma cohort was invited to a follow-up including spirometry, blood sampling, and structured interviews, and n = 892 participated (55% women, mean age 59 y, 32-92 y). Blood eosinophils, neutrophils and FEV 1 decline were analyzed both as continuous variables and divided into categories with different cut-offs. Regression models adjusted for smoking, exposure to vapors, gas, dust, or fumes (VGDF), use of inhaled and oral corticosteroids, and other possible confounders were utilized to analyze the relationship between eosinophils and neutrophils at follow-up and FEV1 decline.

    Results: The mean follow-up time was 18 years, and the mean FEV 1 decline was 27 ml/year. The annual FEV1 decline was related to higher levels of both blood eosinophils and neutrophils at follow-up, but only the association with eosinophils remained when adjusted for confounders. Further, the association between FEV1 decline and eosinophils was stronger among those using ICS. With EOS <0.3 × 109/L as reference, a more rapid decline in FEV1 was independently related to EOS ≥0.4 × 109/L in adjusted analyses.

    Conclusions and clinical relevance: Besides emphasizing the importance of smoking cessation and reduction of other harmful exposures, our real-world results indicate that there is an independent relationship between blood eosinophils and FEV1 decline among adults with asthma.

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  • 15. Baharom, Faezzah
    et al.
    Rankin, Gregory
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Smed-Sorensen, Anna
    Human Lung Mononuclear Phagocytes in Health and Disease2017In: Frontiers in Immunology, ISSN 1664-3224, E-ISSN 1664-3224, Vol. 8, article id 499Article, review/survey (Refereed)
    Abstract [en]

    The lungs are vulnerable to attack by respiratory insults such as toxins, allergens, and pathogens, given their continuous exposure to the air we breathe. Our immune system has evolved to provide protection against an array of potential threats without causing collateral damage to the lung tissue. In order to swiftly detect invading pathogens, monocytes, macrophages, and dendritic cells (DCs)-together termed mononuclear phagocytes (MNPs)-line the respiratory tract with the key task of surveying the lung microenvironment in order to discriminate between harmless and harmful antigens and initiate immune responses when necessary. Each cell type excels at specific tasks: monocytes produce large amounts of cytokines, macrophages are highly phagocytic, whereas DCs excel at activating naive T cells. Extensive studies in murine models have established a division of labor between the different populations of MNPs at steady state and during infection or inflammation. However, a translation of important findings in mice is only beginning to be explored in humans, given the challenge of working with rare cells in inaccessible human tissues. Important progress has been made in recent years on the phenotype and function of human lung MNPs. In addition to a substantial population of alveolar macrophages, three subsets of DCs have been identified in the human airways at steady state. More recently, monocyte-derived cells have also been described in healthy human lungs. Depending on the source of samples, such as lung tissue resections or bronchoalveolar lavage, the specific subsets of MNPs recovered may differ. This review provides an update on existing studies investigating human respiratory MNP populations during health and disease. Often, inflammatory MNPs are found to accumulate in the lungs of patients with pulmonary conditions. In respiratory infections or inflammatory diseases, this may contribute to disease severity, but in cancer patients this may improve clinical outcomes. By expanding on this knowledge, specific lung MNPs may be targeted or modulated in order to attain favorable responses that can improve preventive or treatment strategies against respiratory infections, lung cancer, or lung inflammatory diseases.

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  • 16. Bajraktari, G. Gani
    et al.
    Bytyci, I.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Henein, Mark
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    LA diameter more than 40 mm predicts recurrence of atrial fibrillation after trans-catheter ablation: a systematic review and meta-analysis2017In: European Journal of Heart Failure, ISSN 1388-9842, E-ISSN 1879-0844, Vol. 19, no S1, p. 431-432, article id P1758Article in journal (Refereed)
    Abstract [en]

    Background and Aim: Left atrial (LA) enlargement is associated with atrial fibrillation (AF) incidence and outcome. Trans-catheter ablation of AF has now become a conventional treatment of AF but its recurrence remains of clinical significance. The predictive role of the LA size in AF treatment is still controversial, hence the aim of this meta-analysis was to analyze the potential association between LA diameter and AF recurrence after ablation.

    Methods: We systematically searched PubMed-Medline, EMBASE, Scopus, Google Scholar and the Cochrane Central Registry, up to December 2016 in order to select clinical trial and observational studies, which assessed the predictive role of LA diameter in AF recurrence after catheter-ablation. 13.573 patients from 61 studies with paroxysmal AF (PAF), persistent (PeAF) or longstanding persistent AF (L-PeAF) were included.

    Results: The pooled analysis showed that after a follow-up period of 19± 7.74 months, patients with AF recurrence had larger LA size compared with those without AF recurrence, with a weighted mean difference (WMD) 0.49 ([95% CI 0.39 to 0.59], P < 0.001), irrespective of the type of AF. A subgroup analysis showed LA diameter to be different; WMD was 2.29 ([95% CI 1.31 to 3.26], P < 0.001) in PAF and 1.51 ([95% CI 1.10 to 1.93], P < 0.001) in PeAF/L-PeAF, the difference between these two subgroups was not significant (Chi2=2.04, I2=51.1%, p=0.15). LA diameter ≥40 mm predicted AF recurrence HR:1.08 [95% CI 1.03 to 1.14], P=0.006), but the best cut-off value, in all included patients, was ≥50mm HR:2.73 [95% CI 1.64 to 4.55], P<0.001).

    Conclusions: Increased LA diameter significantly predicts recurrence of AF after ablation procedure. While a diameter of 40 mm predicts recurrence, a diameter more than 50 mm is the most accurate predictor.

  • 17. Bajraktari, G. Gani
    et al.
    Bytyci, I.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Henein, Mark
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Reduced LA strain predicts atrial fibrillation recurrence after catheter ablation: a systematic review and meta-analysis2017In: European Journal of Heart Failure, ISSN 1388-9842, E-ISSN 1879-0844, Vol. 19, no S1, p. 430-431, article id P1755Article in journal (Refereed)
    Abstract [en]

    Background and Aim: Despite the improved outcome of patients with atrial fibrillation (AF) who undergo catheter ablation, recurrence of the arrhythmia remains a concern. The aim of this meta-analysis was to assess the potential association between left atrial (LA) strain and AF recurrence after ablation.

    Methods: We systematically searched PubMed-Medline, EMBASE, Scopus, Google Scholar and the Cochrane Central Registry, up to December 2016 in order to identify clinical trial and observational studies, which assessed the predictive role of LA strain in AF recurrence after catheter-ablation. The search identified 898 patients form 10 studies, with paroxysmal AF (PAF) and persistent AF (PeAF).

    Results: The pooled analysis showed that after a follow-up period of 11.8± 8.1 months, patients with AF recurrence had reduced LA strain compared with those without AF, with a weighted mean difference (WMD) -7.04% ([95% CI -9.62 to -4.45], P < 0.0001). A subgroup analysis showed that LA strain was reduced regardless of AF type; WMD was -5.47% ([95% CI -9.82% to -1.13%], P=0.003) in PAF and -7.88% ([95% CI -11.19% to -4.56%], P < 0.001) in PAF/PeAF, the difference between these two subgroups was not significant (Chi2=0.75, I2=0.0%, p=0.39). A cut off value of 21% [6% to 30%], was 79% [65-86%] sensitive and 77% [66% to 91%] specific for predicting AF recurrence.

    Conclusions: Reduced LA strain significantly predicts recurrence of AF after ablation procedure, irrespective of AF type. This emphasizes the impact of LA wall remodeling on successful ablation.

  • 18.
    Bajraktari, Gani
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine. Clinic of Cardiology, University Clinical Centre of Kosova; Department of Internal Medicine, Medical Faculty, University of Prishtina, Prishtina, Republic of Kosovo.
    Jashari, Haki
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine. Clinic of Cardiology, University Clinical Centre of Kosova.
    Ibrahimi, Pranvera
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine. Clinic of Cardiology, University Clinical Centre of Kosova.
    Alfonso, Fernando
    Jashari, Fisnik
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine. Department of Internal Medicine, Medical Faculty, University of Prishtina, Prishtina, Republic of Kosovo.
    Ndrepepa, Gjin
    Elezi, Shpend
    Henein, Michael Y.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine. St George University, London, UK.
    Complete revascularization for patients with ST-segment elevation myocardial infarction and multivessel coronary artery disease: a meta-analysis of randomized trials2018In: Coronary Artery Disease, ISSN 0954-6928, E-ISSN 1473-5830, Vol. 29, no 3, p. 204-215Article in journal (Refereed)
    Abstract [en]

    Introduction: Despite the recent findings in randomized clinical trials (RCTs) with limited sample sizes and the updates in clinical guidelines, the current available data for the complete revascularization (CR) in hemodynamically stable patients with ST-segment elevation myocardial infarction (STEMI) at the time of primary percutaneous coronary intervention (PCI) are still contradictory.

    Aim: The aim of this meta-analysis of the existing RCTs was to assess the efficacy of the CR versus revascularization of infarct-related artery (IRA) only during primary PCI in patients with STEMI and multivessel disease (MVD).

    Patients and methods: We searched PubMed, MEDLINE, Embase, Scopus, Google Scholar, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov databases aiming to find RCTs for patients with STEMI and MVD which compared CR with IRA-only. Random effect risk ratios (RRs) were calculated for efficacy and safety outcomes.

    Results: Ten RCTs with 3291 patients were included. The median follow-up duration was 17.5 months. Major adverse cardiac events (RR=0.57; 0.43-0.76; P<0.0001), cardiac mortality (RR=0.52; 0.31-0.87; P=0.014), and repeat revascularization (RR=0.50; 0.30-0.84; P=0.009) were lower in CR compared with IRA-only strategies. However, there was no significant difference in the risk of all-cause mortality, recurrent nonfatal myocardial infarction, stroke, major bleeding events, and contrast-induced nephropathy.

    Conclusion: For patients with STEMI and MVD undergoing primary PCI, the current evidence suggests that the risk of major adverse cardiac events, repeat revascularization, and cardiac death is reduced by CR. However, the risk for all-cause mortality and PCI-related complications is not different from the isolated culprit lesion-only treatment. Although these findings support the cardiac mortality and safety benefit of CR in stable STEMI, further large trials are required to provide better guidance for optimum management of such patients.

  • 19.
    Bajraktari, Gani
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology. Heart Centre, Umeå.
    Pugliese, Nicola Riccardo
    D'Agostino, Andreina
    Rosa, Gian Marco
    Ibrahimi, Pranvera
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology. Heart Centre, Umeå.
    Perçuku, Luan
    Miccoli, Mario
    Galeotti, Gian Giacomo
    Fabiani, Iacopo
    Pedrinelli, Roberto
    Henein, Michael
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology. Heart Centre, Umeå.
    Dini, Frank L.
    Echo- and B-Type Natriuretic Peptide-Guided Follow-Up versus Symptom-Guided Follow-Up: Comparison of the Outcome in Ambulatory Heart Failure Patients2018In: Cardiology Research and Practice, ISSN 2090-8016, E-ISSN 2090-0597, article id 3139861Article in journal (Refereed)
    Abstract [en]

    Recent European Society of Cardiology and American Heart Association/American College of Cardiology Guidelines did not recommend biomarker-guided therapy in the management of heart failure (HF) patients. Combination of echo- and B-type natriuretic peptide (BNP) may be an alternative approach in guiding ambulatory HF management. Our aim was to determine whether a therapy guided by echo markers of left ventricular filling pressure (LVFP), lung ultrasound (LUS) assessment of B-lines, and BNP improves outcomes of HF patients. Consecutive outpatients with LV ejection fraction (EF) <= 50% have been prospectively enrolled. In Group I (n=224), follow-up was guided by echo and BNP with the goal of achieving E-wave deceleration time (EDT) >= 150 ms, tissue Doppler index E/e' < 13, B-line numbers < 15, and BNP <= 125 pg/ml or decrease > 30%; in Group II (n=293), follow-up was clinically guided, while the remaining 277 patients (Group III) did not receive any dedicated follow-up. At 60 months, survival was 88% in Group I compared to 75% in Group II and 54% in Group III (chi(2) 53.5; p<0.0001). Survival curves exhibited statistically significant differences using Mantel-Cox analysis. The number needed to treat to spare one death was 7.9 (Group I versus Group II) and 3.8 (Group I versus Group III). At multivariate Cox regression analyses, major predictors of all-cause mortality were follow-up E/e' (HR: 1.05; p=0.0038) and BNP > 125 pg/ml or decrease <= 30% (HR: 4.90; p=0.0054), while BNP > 125 pg/ml or decrease <= 30% and B-line numbers >= 15 were associated with the combined end point of death and HF hospitalization. Evidence-based HF treatment guided by serum biomarkers and ultrasound with the goal of reducing elevated BNP and LVFP, and resolving pulmonary congestion was associated with better clinical outcomes and can be valuable in guiding ambulatory HF management.

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  • 20. Bals, Robert
    et al.
    Boyd, Jeanette
    Esposito, Susanna
    Foronjy, Robert
    Hiemstra, Pieter S.
    Jimenez-Ruiz, Carlos A.
    Katsaounou, Paraskevi
    Lindberg, Anne
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Metz, Carlos
    Schober, Wolfgang
    Spira, Avrum
    Blasi, Francesco
    Electronic cigarettes: a task force report from the European Respiratory Society2019In: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 53, no 2, article id 1801151Article in journal (Refereed)
    Abstract [en]

    There is a marked increase in the development and use of electronic nicotine delivery systems or electronic cigarettes (ECIGs). This statement covers electronic cigarettes (ECIGs), defined as "electrical devices that generate an aerosol from a liquid" and thus excludes devices that contain tobacco. Database searches identified published articles that were used to summarise the current knowledge on the epidemiology of ECIG use; their ingredients and accompanied health effects; second-hand exposure; use of ECIGs for smoking cessation; behavioural aspects of ECIGs and social impact; in vitro and animal studies; and user perspectives. ECIG aerosol contains potentially toxic chemicals. As compared to conventional cigarettes, these are fewer and generally in lower concentrations. Second-hand exposures to ECIG chemicals may represent a potential risk, especially to vulnerable populations. There is not enough scientific evidence to support ECIGs as an aid to smoking cessation due to a lack of controlled trials, including those that compare ECIGs with licenced stop-smoking treatments. So far, there are conflicting data that use of ECIGs results in a renormalisation of smoking behaviour or for the gateway hypothesis. Experiments in cell cultures and animal studies show that ECIGs can have multiple negative effects. The long-term effects of ECIG use are unknown, and there is therefore no evidence that ECIGs are safer than tobacco in the long term. Based on current knowledge, negative health effects cannot be ruled out.

  • 21. Batalli, A.
    et al.
    Ibrahimi, P.
    Bytyci, I
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Ahmeti, A.
    Haliti, E.
    Elezi, S.
    Henein, Mark
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Bajraktari, G. Gani
    Different predictors of exercise capacity in HFpEF compared to HFrEF2017In: European Journal of Heart Failure, ISSN 1388-9842, E-ISSN 1879-0844, Vol. 19, no 1, p. 314-314, article id P1244Article in journal (Refereed)
    Abstract [en]

    Background and Aim: Quality of life is as important as survival in heart failure (HF) patients. Controversies exist with regards to echocardiographic predictors of exercise capacity in HF, particularly in patients with preserved ejection fraction (HFpEF). The aim of this study was to prospectively examine echocardiographic parameters that correlate and predict functional exercise capacity assessed by 6 min walk test (6-MWT) in patients with HFpEF.

    Methods: In 111 HF patients (mean age 63± 10 years, 47% female), an echo-Doppler study and a 6-MWT were performed in the same day. Patients were divided into two groups based on the 6-MWT distance (Group I: ≤ 300 m and Group II: >300 m).

    Results: Group I were older (p=0.008), had higher prevalence of diabetes (p=0.027), higher baseline heart rate (p=0.004), larger left atrium - LA (p=0.001), longer LV filling time - FT (p=0.019), shorter isovolumic relaxation time (p=0.037), shorter pulmonary acceleration time - PAAT (p=0.006), lower left atrial lateral wall myocardial velocity (a’) (p=0.018) and lower septal systolic myocardial velocity (s’) (p=0.023), compared with Group II. Patients with HF and reduced EF (HFrEF) had lower hemoglobin (p=0.007), higher baseline heart rate (p=0.005), higher NT-ProBNP (p=0.001), larger LA (p=0.004), lower septal s’, e’, a’ waves, and septal MAPSE, shorter PAAT (p < 0.001 for all), lower lateral MAPSE, higher E/A & E/e’, and shorter LVFT (p=0.001 for all), lower lateral e’ (p=0.009), s’ (p=0.006), RV e’ and LA emptying fraction (p=0.012 for both), compared with HFpEF patients. In multivariate analysis, only LA diameter [2.676 (1.242-5.766), p=0.012], and diabetes [0.274 (0.084 - 0.898), p=0.033] independently predicted poor 6-MWT performance in the group as a whole. In HFrEF, age [1.073 (1.012 - 1.137), p=0.018] and LA diameter [3.685 (1.348 - 10.071), p=0.011], but in HFpEF, lateral s’ [0.295 (0.099 - 0.882), p=0.029], and hemoglobin level [0.497 (0.248-0.998), p=0.049] independently predicted poor 6-MWT performance.

    Conclusion: In HF patients predictors of exercise capacity differ according to severity of overall LV systolic function, with left atrial enlargement in HFrEF and longitudinal systolic shortening in HFpEF as the the main predictors.

  • 22. Batalli, Arlind
    et al.
    Ibrahimi, Pranvera
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology. Clinic of Cardiology, University Clinical Centre of Kosova, "Rrethi i Spitalit", p.n., Prishtina, Kosovo.
    Bytyçi, Ibadete
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Ahmeti, Artan
    Haliti, Edmond
    Elezi, Shpend
    Henein, Michael Y
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology. Molecular and Clinical Sciences Research Institute, St George University London, London, United Kingdom.
    Bajraktari, Gani
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology. Clinic of Cardiology, University Clinical Centre of Kosova, “Rrethi i Spitalit”, p.n., Prishtina, Kosovo; Medical Faculty, University of Prishtina, Prishtina, Kosovo.
    Different determinants of exercise capacity in HFpEF compared to HFrEF2017In: Cardiovascular Ultrasound, ISSN 1476-7120, E-ISSN 1476-7120, Vol. 15, no 1, article id 12Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Quality of life is as important as survival in heart failure (HF) patients. Controversies exist with regards to echocardiographic determinants of exercise capacity in HF, particularly in patients with preserved ejection fraction (HFpEF). The aim of this study was to prospectively examine echocardiographic parameters that correlate and predict functional exercise capacity assessed by 6 min walk test (6-MWT) in patients with HFpEF.

    METHODS: In 111 HF patients (mean age 63 ± 10 years, 47% female), an echo-Doppler study and a 6-MWT were performed in the same day. Patients were divided into two groups based on the 6-MWT distance (Group I: ≤ 300 m and Group II: >300 m).

    RESULTS: Group I were older (p = 0.008), had higher prevalence of diabetes (p = 0.027), higher baseline heart rate (p = 0.004), larger left atrium - LA (p = 0.001), longer LV filling time - FT (p = 0.019), shorter isovolumic relaxation time (p = 0.037), shorter pulmonary artery acceleration time - PA acceleration time (p = 0.006), lower left atrial lateral wall myocardial velocity (a') (p = 0.018) and lower septal systolic myocardial velocity (s') (p = 0.023), compared with Group II. Patients with HF and reduced EF (HFrEF) had lower hemoglobin (p = 0.007), higher baseline heart rate (p = 0.005), higher NT-ProBNP (p = 0.001), larger LA (p = 0.004), lower septal s', e', a' waves, and septal mitral annular plane systolic excursion (MAPSE), shorter PA acceleration time (p < 0.001 for all), lower lateral MAPSE, higher E/A & E/e', and shorter LVFT (p = 0.001 for all), lower lateral e' (p = 0.009), s' (p = 0.006), right ventricular e' and LA emptying fraction (p = 0.012 for both), compared with HFpEF patients. In multivariate analysis, only LA diameter [2.676 (1.242-5.766), p = 0.012], and diabetes [0.274 (0.084-0.898), p = 0.033] independently predicted poor 6-MWT performance in the group as a whole. In HFrEF, age [1.073 (1.012-1.137), p = 0.018] and LA diameter [3.685 (1.348-10.071), p = 0.011], but in HFpEF, lateral s' [0.295 (0.099-0.882), p = 0.029], and hemoglobin level [0.497 (0.248-0.998), p = 0.049] independently predicted poor 6-MWT performance.

    CONCLUSIONS: In HF patients determinants of exercise capacity differ according to severity of overall LV systolic function, with left atrial enlargement in HFrEF and longitudinal systolic shortening in HFpEF as the the main determinants.

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  • 23. Baumeister, Sebastian E.
    et al.
    Schlesinger, Sabrina
    Aleksandrova, Krasimira
    Jochem, Carmen
    Jenab, Mazda
    Gunter, Marc J.
    Overvad, Kim
    Tjonneland, Anne
    Boutron-Ruault, Marie-Christine
    Carbonnel, Franck
    Fournier, Agnes
    Kuehn, Tilman
    Kaaks, Rudolf
    Pischon, Tobias
    Boeing, Heiner
    Trichopoulou, Antonia
    Bamia, Christina
    La Vecchia, Carlo
    Masala, Giovanna
    Panico, Salvatore
    Fasanelli, Francesca
    Tumino, Rosario
    Grioni, Sara
    de Mesquita, Bas Bueno
    Vermeulen, Roel
    May, Anne M.
    Borch, Kristin B.
    Oyeyemi, Sunday O.
    Ardanaz, Eva
    Rodriguez-Barranco, Miguel
    Chirlaque Lopez, Maria Dolores
    Felez-Nobrega, Mireia
    Sonestedt, Emily
    Ohlsson, Bodil
    Hemmingsson, Oskar
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Werner, Mårten
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Perez-Cornago, Aurora
    Ferrari, Pietro
    Stepien, Magdalena
    Freisling, Heinz
    Tsilidis, Konstantinos K.
    Ward, Heather
    Riboli, Elio
    Weiderpass, Elisabete
    Leitzmann, Michael F.
    Association between physical activity and risk of hepatobiliary cancers: A multinational cohort study2019In: Journal of Hepatology, ISSN 0168-8278, E-ISSN 1600-0641, Vol. 70, no 5, p. 885-892Article in journal (Refereed)
    Abstract [en]

    Background & Aims: To date, evidence on the association between physical activity and risk of hepatobiliary cancers has been inconclusive. We examined this association in the European Prospective Investigation into Cancer and Nutrition cohort (EPIC).

    Methods: We identified 275 hepatocellular carcinoma (HCC) cases, 93 intrahepatic bile duct cancers (IHBCs), and 164 non-gallbladder extrahepatic bile duct cancers (NGBCs) among 467,336 EPIC participants (median follow-up 14.9 years). We estimated cause-specific hazard ratios (HRs) for total physical activity and vigorous physical activity and performed mediation analysis and secondary analyses to assess robustness to confounding (e.g. due to hepatitis virus infection).

    Results: In the EPIC cohort, the multivariable-adjusted HR of HCC was 0.55 (95% CI 0.38–0.80) comparing active and inactive individuals. Regarding vigorous physical activity, for those reporting >2 hours/week compared to those with no vigorous activity, the HR for HCC was 0.50 (95% CI 0.33–0.76). Estimates were similar in sensitivity analyses for confounding. Total and vigorous physical activity were unrelated to IHBC and NGBC. In mediation analysis, waist circumference explained about 40% and body mass index 30% of the overall association of total physical activity and HCC.

    Conclusions: These findings suggest an inverse association between physical activity and risk of HCC, which is potentially mediated by obesity.

    Lay summary: In a pan-European study of 467,336 men and women, we found that physical activity is associated with a reduced risk of developing liver cancers over the next decade. This risk was independent of other liver cancer risk factors, and did not vary by age, gender, smoking status, body weight, and alcohol consumption.

  • 24.
    Bay, Annika
    et al.
    Umeå University, Faculty of Medicine, Department of Nursing. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Lämås, Kristina
    Umeå University, Faculty of Medicine, Department of Nursing.
    Berghammer, Malin
    Sandberg, Camilla
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Johansson, Bengt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    It ́s like balancing on a slackline: A description from adults living with congenital heart disease2018In: Cardiology in the Young, ISSN 1047-9511, E-ISSN 1467-1107, Vol. 28, no Suppl. S1, p. S37-S37Article in journal (Refereed)
    Abstract [en]

    Introduction: Several studies have shown that adults with congenital heart disease have reduced exercise capacity and do not reach the recommended daily level of physical activity. With this in view, it is of great importance to investigate how this population experiences physical activity. The aim of the study is to illuminate how adults with congenital heart disease describes themselves in relation to physical activity.

    Methods: Semi-structured interviews with fourteen adults with complex congenital heart disease were performed. Patients were recruited from the clinic waiting list, based on their scheduled follow up and diagnosis. Interviews were analysed by qualitative content analysis.

    Results: The overall theme It´s like balancing on a slackline illustrates how adults with congenital heart disease described themselves in relation to physical activity. The overall theme consists of four themes: Being an adventurer- enjoying the challenges of physical activity, Being a realist- adapting to physical ability, Beinga non-doer- lacking prerequisites for physical activity and Being an outsider- feeling excluded depending on physical ability.

    Conclusions: The descriptions on themselves as a physically active were not constant or one-dimensional and the descriptions varied during the interviews, related to different time periods in life. It meant that they could described themselves as being an adventurer liking tough challenges, but at the same time describing themselves as being a non-doer with uncertainty over their physical strength. The findings point out specific factors for adults with CHD that might constitute as obstacles, but also possibilities for being physically active.

  • 25.
    Bay, Annika
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Sandberg, Camilla
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Thilen, U.
    Wadell, Karin
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Physiotherapy.
    Johansson, Bengt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Exercise self-efficacy (ESE) in adults with congential heart disease2017In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 38, no Suppl. 1, article id ehx501.P618Article in journal (Refereed)
    Abstract [en]

    Background: Many adults with congenital heart disease (CHD) have reduced aerobic exercise capacity and impaired muscle function. However, it is largely unknown which factors have influence on the confidence to perform exercise training, i.e. Exercise Self-Efficacy (ESE).

    Aims: To identify factors related to low ESE, and thus identify potential targets for rehabilitation and thereby enhance the potential for being physically active.

    Methods: Seventy-nine adults with CHD; simple lesions n=38 (women n=16), complex lesions n=41 (women n=17) (mean age 36.7±14.6 years) and 42 age and sex matched controls were recruited. All participants completed questionnaires on ESE, quality of life (EQ-5D), and physical activity (international physical activity questionnaire, IPAQ), and performed muscle endurance tests.

    Results: ESE was categorised into low (<26 points, n=24) and high (≥26 points, n=55). Patients with low ESE were older (45.2±15.4 vs. 32.6±12.5 years, p=0.002), more often had prescribed medication (67% vs. 44%, p=0.06), higher New York Heart Association functional class (NYHA) (≥ III) (25% vs. 7%, p=0.03) and performed fewer shoulder flexions (30.9±16.1 vs. 45.9±23.9, p=0.01) compared with those with high ESE. In the high ESE group, ESE did not differ from controls (33.8±3.9 vs. 33.4±6.1, p=0.74). In linear multivariate analysis age (B;-0.18, 95% CI -0.28- -0.08), smoking (B;-3.73, 95% CI -7.17- -0.28), EQ-5Dindex <1 (B;-3.33, 95% CI -6.08- -0.57) and number of shoulder flexions (B; 0.09, 95% CI 0.03–0.16) were independently associated with ESE.

    Conclusion: Many adults with CHD have low ESE. Rehabilitation targeting quality of life, smoking cessation and muscle training may improve ESE, and thus enhance the potential for being physically active in this population.

  • 26.
    Behndig, Annelie F.
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Mirgorodskaya, Ekaterina
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Olin, Anna-Carin
    Surfactant Protein A in particles in exhaled air (PExA), bronchial lavage and bronchial wash - a methodological comparison2019In: Respiratory Research, ISSN 1465-9921, E-ISSN 1465-993X, Vol. 20, no 1, article id 214Article in journal (Refereed)
    Abstract [en]

    Introduction: At present, there are few methods available for monitoring respiratory diseases affecting distal airways. Bronchoscopy is the golden standard for sampling the lower airways. The recently developed method for collecting non-volatile material from exhaled air – PExA (Particles in Exhaled air) is a promising new tool, but no direct comparison between the two methods has yet been performed. The aim of the present study was to compare sampling using PExA with bronchial wash (BW) representing the larger more proximal airways and broncho-alveolar lavage (BAL) representing the distal airways.

    Methods: 15 healthy non-smoking subjects (7 female/8 male), age 28 ± 4 years, with normal lung function were included in the study. PExA-sampling (2 × 250 ng particles) and bronchoscopy with BW (2 × 20 ml) and BAL (3 × 60 ml sterile saline) was performed. Albumin and Surfactant Protein A (SP-A) were analyzed with ELISA, and analyses of correlation were performed.

    Results: A significant association was found between BAL-fluid albumin and PExA-albumin (rs:0.65 p = 0.01). There was also an association between SP-A in PExA and BAL, when corrected for albumin concentration (rs:0.61, p = 0.015). When correlating concentrations of albumin and SP-A in bronchial wash and PExA respectively, no associations were found.

    Conclusions: This is the first direct comparison between the bronchoscopy-based BW/BAL-fluids and material collected using the PExA methodology. Both albumin and albumin-corrected SP-A concentrations were significantly associated between BAL and PExA, however, no such association was found in either marker between BW and PExA. These results indicate that the PExA method samples the distal airways. PExA is thus considered a new promising non-invasive assessment for monitoring of the distal airways.

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  • 27. Bennet, Louise
    et al.
    Franks, Paul W.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine. Department of Clinical Sciences, Lund University, Skåne University Hospital, Malmö, Sweden; Department of Diabetes and Endocrinology/Lund University Diabetes Centre, Skåne University Hospital, Malmö, Sweden; Genetic and Molecular Epidemiology Unit, Lund University, Malmö, Sweden; Department of Nutrition, Harvard School of Public Health, Boston, MA, USA.
    Zöller, Bengt
    Groop, Leif
    Family history of diabetes and its relationship with insulin secretion and insulin sensitivity in Iraqi immigrants and native Swedes: a population-based cohort study2018In: Acta Diabetologica, ISSN 0940-5429, E-ISSN 1432-5233, Vol. 55, no 3, p. 233-242Article in journal (Refereed)
    Abstract [en]

    Aims Middle Eastern immigrants to western countries are at high risk of developing type 2 diabetes. However, the heritability and impact of rst-degree family history (FH) of type 2 diabetes on insulin secretion and action have not been adequately described. Methods Citizens of Malmö, Sweden, aged 30–75 years born in Iraq or Sweden were invited to participate in this population- based study. Insulin secretion (corrected insulin response and oral disposition index) and action (insulin sensitivity index) were assessed by oral glucose tolerance tests.

    Results In total, 45.7% of Iraqis (616/1348) and 27.4% of native Swedes (201/733) had FH in parent(s), sibling(s) or single parent and sibling, i.e., FH+. Approximately 8% of Iraqis and 0.7% of Swedes had ≥ 3 sibling(s) and parent(s) with diabetes, i.e., FH++. Irrespective of family size, prediabetes and diabetes increased with family burden (FH− 29.4%; FH+ 38.8%; FH++ 61.7%) without signi cant di erences across ethnicities. With increasing level of family burden, insulin secretion rather than insulin action decreased. Individuals with a combination of ≥ 3 siblings and parents with diabetes presented with the lowest levels of insulin secretion.

    Conclusions The Iraqi immigrant population often present with a strong familial burden of type 2 diabetes with the worst glycemic control and highest diabetes risk in individuals with ≥ 3 siblings and parents with diabetes. Our data show that in a population still free from diabetes familial burden in uences insulin secretion to a higher degree than insulin action and may be a logical target for intervention. 

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  • 28. Bentley, Amy R.
    et al.
    Sung, Yun J.
    Brown, Michael R.
    Winkler, Thomas W.
    Kraja, Aldi T.
    Ntalla, Ioanna
    Schwander, Karen
    Chasman, Daniel, I
    Lim, Elise
    Deng, Xuan
    Guo, Xiuqing
    Liu, Jingmin
    Lu, Yingchang
    Cheng, Ching-Yu
    Sim, Xueling
    Vojinovic, Dina
    Huffman, Jennifer E.
    Musani, Solomon K.
    Li, Changwei
    Feitosa, Mary F.
    Richard, Melissa A.
    Noordam, Raymond
    Baker, Jenna
    Chen, Guanjie
    Aschard, Hugues
    Bartz, Traci M.
    Ding, Jingzhong
    Dorajoo, Rajkumar
    Manning, Alisa K.
    Rankinen, Tuomo
    Smith, Albert, V
    Tajuddin, Salman M.
    Zhao, Wei
    Graff, Mariaelisa
    Alver, Maris
    Boissel, Mathilde
    Chai, Jin Fang
    Chen, Xu
    Divers, Jasmin
    Evangelou, Evangelos
    Gao, Chuan
    Goel, Anuj
    Hagemeijer, Yanick
    Harris, Sarah E.
    Hartwig, Fernando P.
    He, Meian
    Horimoto, Andrea R. V. R.
    Hsu, Fang-Chi
    Hung, Yi-Jen
    Jackson, Anne U.
    Kasturiratne, Anuradhani
    Komulainen, Pirjo
    Kuehnel, Brigitte
    Leander, Karin
    Lin, Keng-Hung
    Luan, Jian'an
    Lyytikainen, Leo-Pekka
    Matoba, Nana
    Nolte, Ilja M.
    Pietzner, Maik
    Prins, Bram
    Riaz, Muhammad
    Robino, Antonietta
    Said, M. Abdullah
    Schupf, Nicole
    Scott, Robert A.
    Sofer, Tamar
    Stancakova, Alena
    Takeuchi, Fumihiko
    Tayo, Bamidele O.
    van der Most, Peter J.
    Varga, Tibor V.
    Wang, Tzung-Dau
    Wang, Yajuan
    Ware, Erin B.
    Wen, Wanqing
    Xiang, Yong-Bing
    Yanek, Lisa R.
    Zhang, Weihua
    Zhao, Jing Hua
    Adeyemo, Adebowale
    Afaq, Saima
    Amin, Najaf
    Amini, Marzyeh
    Arking, Dan E.
    Arzumanyan, Zorayr
    Aung, Tin
    Ballantyne, Christie
    Barr, R. Graham
    Bielak, Lawrence F.
    Boerwinkle, Eric
    Bottinger, Erwin P.
    Broeckel, Ulrich
    Brown, Morris
    Cade, Brian E.
    Campbell, Archie
    Canouil, Mickael
    Charumathi, Sabanayagam
    Chen, Yii-Der Ida
    Christensen, Kaare
    Concas, Maria Pina
    Connell, John M.
    de las Fuentes, Lisa
    de Silva, H. Janaka
    de Vries, Paul S.
    Doumatey, Ayo
    Duan, Qing
    Eaton, Charles B.
    Eppinga, Ruben N.
    Faul, Jessica D.
    Floyd, James S.
    Forouhi, Nita G.
    Forrester, Terrence
    Friedlander, Yechiel
    Gandin, Ilaria
    Gao, He
    Ghanbari, Mohsen
    Gharib, Sina A.
    Gigante, Bruna
    Giulianini, Franco
    Grabe, Hans J.
    Gu, C. Charles
    Harris, Tamara B.
    Heikkinen, Sami
    Heng, Chew-Kiat
    Hirata, Makoto
    Hixson, James E.
    Ikram, M. Arfan
    Jia, Yucheng
    Joehanes, Roby
    Johnson, Craig
    Jonas, Jost Bruno
    Justice, Anne E.
    Katsuya, Tomohiro
    Khor, Chiea Chuen
    Kilpelainen, Tuomas O.
    Koh, Woon-Puay
    Kolcic, Ivana
    Kooperberg, Charles
    Krieger, Jose E.
    Kritchevsky, Stephen B.
    Kubo, Michiaki
    Kuusisto, Johanna
    Lakka, Timo A.
    Langefeld, Carl D.
    Langenberg, Claudia
    Launer, Lenore J.
    Lehne, Benjamin
    Lewis, Cora E.
    Li, Yize
    Liang, Jingjing
    Lin, Shiow
    Liu, Ching-Ti
    Liu, Jianjun
    Liu, Kiang
    Loh, Marie
    Lohman, Kurt K.
    Louie, Tin
    Luzzi, Anna
    Magi, Reedik
    Mahajan, Anubha
    Manichaikul, Ani W.
    McKenzie, Colin A.
    Meitinger, Thomas
    Metspalu, Andres
    Milaneschi, Yuri
    Milani, Lili
    Mohlke, Karen L.
    Momozawa, Yukihide
    Morris, Andrew P.
    Murray, Alison D.
    Nalls, Mike A.
    Nauck, Matthias
    Nelson, Christopher P.
    North, Kari E.
    O'Connell, Jeffrey R.
    Palmer, Nicholette D.
    Papanicolau, George J.
    Pedersen, Nancy L.
    Peters, Annette
    Peyser, Patricia A.
    Polasek, Ozren
    Poulter, Neil
    Raitakari, Olli T.
    Reiner, Alex P.
    Renstrom, Frida
    Umeå University, Faculty of Medicine, Department of Biobank Research. Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University Diabetes Centre, Skåne University Hospital, Malmö, Sweden.
    Rice, Treva K.
    Rich, Stephen S.
    Robinson, Jennifer G.
    Rose, Lynda M.
    Rosendaal, Frits R.
    Rudan, Igor
    Schmidt, Carsten O.
    Schreiner, Pamela J.
    Scott, William R.
    Sever, Peter
    Shi, Yuan
    Sidney, Stephen
    Sims, Mario
    Smith, Jennifer A.
    Snieder, Harold
    Starr, John M.
    Strauch, Konstantin
    Stringham, Heather M.
    Tan, Nicholas Y. Q.
    Tang, Hua
    Taylor, Kent D.
    Teo, Yik Ying
    Tham, Yih Chung
    Tiemeier, Henning
    Turner, Stephen T.
    Uitterlinden, Andre G.
    van Heemst, Diana
    Waldenberger, Melanie
    Wang, Heming
    Wang, Lan
    Wang, Lihua
    Wei, Wen Bin
    Williams, Christine A.
    Wilson, Gregory, Sr.
    Wojczynski, Mary K.
    Yao, Jie
    Young, Kristin
    Yu, Caizheng
    Yuan, Jian-Min
    Zhou, Jie
    Zonderman, Alan B.
    Becker, Diane M.
    Boehnke, Michael
    Bowden, Donald W.
    Chambers, John C.
    Cooper, Richard S.
    de Faire, Ulf
    Deary, Ian J.
    Elliott, Paul
    Esko, Tonu
    Farrall, Martin
    Franks, Paul W.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine. Return to work after interdisciplinary pain rehabilitation Department of Gene Diagnostics and Therapeutics, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan; Department of Nutrition, Harvard T. H. Chan School of Public Health, Harvard University, Boston, MA, USA; OCDEM, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
    Freedman, Barry, I
    Froguel, Philippe
    Gasparini, Paolo
    Gieger, Christian
    Horta, Bernardo L.
    Juang, Jyh-Ming Jimmy
    Kamatani, Yoichiro
    Kammerer, Candace M.
    Kato, Norihiro
    Kooner, Jaspal S.
    Laakso, Markku
    Laurie, Cathy C.
    Lee, I-Te
    Lehtimaki, Terho
    Magnusson, Patrik K. E.
    Oldehinkel, Albertine J.
    Penninx, Brenda W. J. H.
    Pereira, Alexandre C.
    Rauramaa, Rainer
    Redline, Susan
    Samani, Nilesh J.
    Scott, James
    Shu, Xiao-Ou
    van der Harst, Pim
    Wagenknecht, Lynne E.
    Wang, Jun-Sing
    Wang, Ya Xing
    Wareham, Nicholas J.
    Watkins, Hugh
    Weir, David R.
    Wickremasinghe, Ananda R.
    Wu, Tangchun
    Zeggini, Eleftheria
    Zheng, Wei
    Bouchard, Claude
    Evans, Michele K.
    Gudnason, Vilmundur
    Kardia, Sharon L. R.
    Liu, Yongmei
    Psaty, Bruce M.
    Ridker, Paul M.
    van Dam, Rob M.
    Mook-Kanamori, Dennis O.
    Fornage, Myriam
    Province, Michael A.
    Kelly, Tanika N.
    Fox, Ervin R.
    Hayward, Caroline
    van Duijn, Cornelia M.
    Tai, E. Shyong
    Wong, Tien Yin
    Loos, Ruth J. F.
    Franceschini, Nora
    Rotter, Jerome, I
    Zhu, Xiaofeng
    Bierut, Laura J.
    Gauderman, W. James
    Rice, Kenneth
    Munroe, Patricia B.
    Morrison, Alanna C.
    Rao, Dabeeru C.
    Rotimi, Charles N.
    Cupples, L. Adrienne
    Multi-ancestry genome-wide gene-smoking interaction study of 387,272 individuals identifies new loci associated with serum lipids2019In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 51, no 4, p. 636-+Article in journal (Refereed)
    Abstract [en]

    The concentrations of high- and low-density-lipoprotein cholesterol and triglycerides are influenced by smoking, but it is unknown whether genetic associations with lipids may be modified by smoking. We conducted a multi-ancestry genome-wide gene-smoking interaction study in 133,805 individuals with follow-up in an additional 253,467 individuals. Combined meta-analyses identified 13 new loci associated with lipids, some of which were detected only because association differed by smoking status. Additionally, we demonstrate the importance of including diverse populations, particularly in studies of interactions with lifestyle factors, where genomic and lifestyle differences by ancestry may contribute to novel findings.

  • 29.
    Bergman, Frida
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Wahlström, Viktoria
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health.
    Stomby, Andreas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Otten, Julia
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Lanthén, Ellen
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Renklint, Rebecka
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Waling, Maria
    Umeå University, Faculty of Social Sciences, Department of Food and Nutrition.
    Sörlin, Ann
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Physiotherapy.
    Boraxbekk, Carl-Johan
    Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR). Danish Research Center for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital, Hvidovre, Denmark.
    Wennberg, Patrik
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Öhberg, Fredrik
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Levine, James A.
    Department of Endocrinology, The Mayo Clinic, Rochester, MN, USA; Fondation IPSEN, Paris, France.
    Olsson, Tommy
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Treadmill workstations in office workers who are overweight or obese: a randomised controlled trial2018In: The Lancet Public Health, ISSN 2468-2667, Vol. 3, no 11, article id e523-e535Article in journal (Refereed)
    Abstract [en]

    Background: Treadmill workstations that enable office workers to walk on a treadmill while working at their computers might increase physical activity in offices, but long-term effects are unknown. We therefore investigated whether treadmill workstations in offices increased daily walking time.

    Methods: We did a randomised controlled trial of healthy office workers who were either overweight or obese. We recruited participants from 13 different companies, which comprised 17 offices, in Umeå, Sweden. We included people who were aged 40-67 years, had sedentary work tasks, and had a body-mass index (BMI) between 25 kg/m2 and 40 kg/m2. After the baseline measurement, we stratified participants by their BMI (25-30 kg/m2 and >30 to 40 kg/m2); subsequently, an external statistician randomly assigned these participants (1:1) to either the intervention group (who received treadmill workstations for optional use) or the control group (who continued to work at their sit-stand desks as usual). Participants in the intervention group received reminders in boosting emails sent out to them at four occasions during the study period. Researchers were masked to group assignment until after analysis of the primary outcome. After the baseline measurement, participants were not masked to group belongings. The primary outcome was total daily walking time at weekdays and weekends, measured at baseline, 2 months, 6 months, 10 months, and 13 months with the accelerometer activPAL (PAL Technologies, Glasgow, UK), which was worn on the thigh of participants for 24 h a day for 7 consecutive days. We used an intention-to-treat approach for our analyses. This trial is registered with ClinicalTrials.gov, number NCT01997970, and is closed to new participants.

    Findings: Between Nov 1, 2013, and June 30, 2014, a total of 80 participants were recruited and enrolled (n=40 in both the intervention and control groups). Daily walking time during total time awake at weekdays increased between baseline and 13 months by 18 min (95% CI 9 to 26) in the intervention group and 1 min (-7 to 9) in the control group (difference 22 min [95% CI 7 to 37], pinteraction=0·00045); for weekend walking, the change from baseline to 13 months was 5 min (-8 to 18) in the intervention group and 8 min (-5 to 21) in the control group (difference -1 min [-19 to 17]; pinteraction=0·00045). Neither measure met our predetermined primary outcome of 30 min difference in total walking time between the intervention and control group, so the primary outcome of the trial was not met. One adverse event was reported in a participant who accidently stepped on their Achilles tendon.

    Interpretation: In a sedentary work environment, treadmill workstations result in a statistically significant but smaller-than-expected increase in daily walking time. Future studies need to investigate how increasing physical activity at work might have potentially compensatory effects on non-work activity.

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  • 30.
    Bergström, Lisa
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Irewall, Anna-Lotta
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Soderstrom, Lars
    Ögren, Joachim
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Laurell, Katarina
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Mooe, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    One-Year Incidence, Time Trends, and Predictors of Recurrent Ischemic Stroke in Sweden From 1998 to 2010 An Observational Study2017In: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 48, no 8, p. 2046-Article in journal (Refereed)
    Abstract [en]

    Background and Purpose-Recent data on the incidence, time trends, and predictors of recurrent ischemic stroke are limited for unselected patient populations. Methods-Data for ischemic stroke patients were obtained from The Swedish Stroke Register (Riksstroke) between 1998 and 2009 and merged with The Swedish National Inpatient Register. A reference group of patients was created by Statistics Sweden. The ischemic stroke patient cohort was divided into 4 time periods. Recurrent ischemic stroke within 1 year was recorded until 2010. Kaplan-Meier and Cox regression analyses were performed to study time trends and predictors of ischemic stroke recurrence. Results-Of 196 765 patients with ischemic stroke, 11.3% had a recurrent ischemic stroke within 1 year. The Kaplan-Meier estimates of the 1-year cumulative incidence of recurrent ischemic stroke decreased from 15.0% in 1998 to 2001 to 12.0% in 2007 to 2010 in the stroke patient cohort while the cumulative incidence of ischemic stroke decreased from 0.7% to 0.4% in the reference population. Age > 75 years, prior ischemic stroke or myocardial infarction, atrial fibrillation without warfarin treatment, diabetes mellitus, and treatment with beta-blockers or diuretics were associated with a higher risk while warfarin treatment for atrial fibrillation, lipid-lowering medication, and antithrombotic treatment (acetylsalicylic acid, dipyridamole) were associated with a reduced risk of recurrent ischemic stroke. Conclusions-The risk of recurrent ischemic stroke decreased from 1998 to 2010. Well-known risk factors for stroke were associated with a higher risk of ischemic stroke recurrence; whereas, secondary preventive medication was associated with a reduced risk, emphasizing the importance of secondary preventive treatment.

  • 31. Bielecka-Dabrowa, Agata
    et al.
    Bytyci, Ibadete
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine. Clinic of Cardiology, University Clinical Centre of Kosovo, Prishtina, Republic of Kosovo.
    Von Haehling, Stephan
    Anker, Stefan
    Jozwiak, Jacek
    Rysz, Jacek
    Hernandez, Adrian V.
    Bajraktari, Gani
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Mikhalidis, Dimitri P.
    Banach, Maciej
    Association of statin use and clinical outcomes in heart failure patients: a systematic review and meta-analysis2019In: Lipids in Health and Disease, ISSN 1476-511X, E-ISSN 1476-511X, Vol. 18, no 1, article id 188Article, review/survey (Refereed)
    Abstract [en]

    Background: The role of statins in patients with heart failure (HF) of different levels of left ventricular ejection fraction (LVEF) remains unclear especially in the light of the absence of prospective data from randomized controlled trials (RCTs) in non-ischemic HF, and taking into account potential statins’ prosarcopenic effects. We assessed the association of statin use with clinical outcomes in patients with HF.

    Methods: We searched PubMed, EMBASE, Scopus, Google Scholar and Cochrane Central until August 2018 for RCTs and prospective cohorts comparing clinical outcomes with statin vs non-statin use in patients with HF at different LVEF levels. We followed the guidelines of the 2009 PRISMA statement for reporting and applied independent extraction by multiple observers. Meta-analyses of hazard ratios (HRs) of effects of statins on clinical outcomes used generic inverse variance method and random model effects. Clinical outcomes were all-cause mortality, cardiovascular (CV) mortality and CV hospitalization.

    Results: Finally we included 17 studies (n = 88,100; 2 RCTs and 15 cohorts) comparing statin vs non-statin users (mean follow-up 36 months). Compared with non-statin use, statin use was associated with lower risk of all-cause mortality (HR 0.77, 95% confidence interval [CI], 0.72–0.83, P < 0.0001, I2 = 63%), CV mortality (HR 0.82, 95% CI: 0.76–0.88, P < 0.0001, I2 = 63%), and CV hospitalization (HR 0.78, 95% CI: 0.69–0.89, P = 0.0003, I2 = 36%). All-cause mortality was reduced on statin therapy in HF with both EF < 40% and ≥ 40% (HR: 0.77, 95% Cl: 0.68–0.86, P < 0.00001, and HR 0.75, 95% CI: 0.69–0.82, P < 0.00001, respectively). Similarly, CV mortality (HR 0.86, 95% CI: 0.79–0.93, P = 0.0003, and HR 0.83, 95% CI: 0.77–0.90, P < 0.00001, respectively), and CV hospitalizations (HR 0.80 95% CI: 0.64–0.99, P = 0.04 and HR 0.76 95% CI: 0.61–0.93, P = 0.009, respectively) were reduced in these EF subgroups. Significant effects on all clinical outcomes were also found in cohort studies’ analyses; the effect was also larger and significant for lipophilic than hydrophilic statins.

    Conclusions: In conclusion, statins may have a beneficial effect on CV outcomes irrespective of HF etiology and LVEF level. Lipophilic statins seem to be much more favorable for patients with heart failure.

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  • 32.
    Björck, Fredrik
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Kadhim, Hayder
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Själander, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Predictors for INR-control in a well-managed warfarin treatment setting2019In: Journal of Thrombosis and Thrombolysis, ISSN 0929-5305, E-ISSN 1573-742X, Vol. 47, no 2, p. 227-232Article in journal (Refereed)
    Abstract [en]

    Warfarin is well studied in patients with non-valvular atrial fibrillation (AF). It has low complication rates for patients achieving individual Time in Therapeutic Range (iTTR)>70%. The risk scores SAMe-TT2R2 and PROSPER are designed to predict future TTR, but are derived from a heterogeneous population with generally low iTTR. The aim of this study was to evaluate predictors for high and low iTTR in an AF population in Sweden, where there is a generally good anticoagulation control. A retrospective register study based on Swedish warfarin dosing system AuriculA, including 28,011 AF patients starting treatment during 1 January 2006 to 31 December 2011. Complications and risk factors were analysed and related to iTTR. Mean age was 73.7 (SD +/- 9.5) years, with 42.0% women. Mean CHA(2)DS(2)-VASc score (SD) was 3.6 (+/- 1.7). For patients with iTTR<60% there were over three times higher prevalence of excessive alcohol consumption than for patients with iTTR>70% (3.7% vs. 1.1%). Previous stroke were more prevalent for patients with high than low iTTR (17.1% vs. 20.3%). Concomitant comorbidities were associated with increased risk of poor iTTR. In Swedish AF patients, excessive alcohol use is clearly associated with iTTR below 60%. Patients with previous stroke are more likely to get iTTR above 70%, unlike those with concomitant disorders who more often have poor anticoagulation control. The SAMe-TT2R2-score cannot be applied in Sweden.

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  • 33.
    Blomstedt, Yulia
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Norberg, Margareta
    Umeå University, Faculty of Medicine, Department of Epidemiology and Global Health.
    Ng, Nawi
    Umeå University, Faculty of Medicine, Department of Epidemiology and Global Health.
    Nyström, Lennarth
    Umeå University, Faculty of Medicine, Department of Epidemiology and Global Health.
    Boman, Kurt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine. Research Unit Medicine-Geriatric Clinic, Skellefteå County Hospital, SE-931 86 Skellefteå, Sweden..
    Lönnberg, Göran
    Umeå University, Faculty of Medicine, Department of Epidemiology and Global Health.
    Stenlund, Hans
    Umeå University, Faculty of Medicine, Department of Epidemiology and Global Health.
    Wall, Stig
    Umeå University, Faculty of Medicine, Department of Epidemiology and Global Health.
    Weinehall, Lars
    Umeå University, Faculty of Medicine, Department of Epidemiology and Global Health.
    Flawed conclusions on the Vasterbotten Intervention Program by San Sebastian et .al2019In: BMC Public Health, ISSN 1471-2458, E-ISSN 1471-2458, Vol. 19, no 1, article id 1095Article in journal (Refereed)
    Abstract [en]

    An evaluation of Vasterbotten Intervention Programme (VIP) was recently conducted by San Sebastian et al. (BMC Public Health 19:202, 2019). Evaluation of health care interventions of this kind require 1) an understanding of both the design and the nature of the intervention, 2) correct definition of the target population, and 3) careful choice of the appropriate evaluation method. In this correspondence, we review the approach used by San Sebastian et al. as relates to these three criteria. Within this framework, we suggest important explanations for why the conclusions drawn by these authors contradict a large body of research on the effectiveness of the VIP.

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  • 34. Blomström-Lundqvist, Carina
    et al.
    Gizurarson, Sigfus
    Schwieler, Jonas
    Jensen, Steen M
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine. Heart Centre, Umeå University, Umeå, Sweden.
    Bergfeldt, Lennart
    Kennebäck, Göran
    Rubulis, Aigars
    Malmborg, Helena
    Raatikainen, Pekka
    Lönnerholm, Stefan
    Höglund, Niklas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine. Heart Centre, Umeå University, Umeå, Sweden.
    Mörtsell, David
    Effect of Catheter Ablation vs Antiarrhythmic Medication on Quality of Life in Patients With Atrial Fibrillation: the CAPTAF Randomized Clinical Trial2019In: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 321, no 11, p. 1059-1068Article in journal (Refereed)
    Abstract [en]

    Importance: Quality of life is not a standard primary outcome in ablation trials, even though symptoms drive the indication.

    Objective: To assess quality of life with catheter ablation vs antiarrhythmic medication at 12 months in patients with atrial fibrillation.

    Design, setting, and participants: Randomized clinical trial at 4 university hospitals in Sweden and 1 in Finland of 155 patients aged 30-70 years with more than 6 months of atrial fibrillation and treatment failure with 1 antiarrhythmic drug or beta-blocker, with 4-year follow-up. Study dateswere July 2008-September 2017. Major exclusionswere ejection fraction <35%, left atrial diameter > 60 mm, ventricular pacing dependency, and previous ablation.

    Interventions: Pulmonary vein isolation ablation (n= 79) or previously untested antiarrhythmic drugs (n= 76).

    Main outcomes and measurement: Primary outcomewas the General Health subscale score (Medical Outcomes Study 36-Item Short-Form Health Survey) at baseline and 12 months, assessed unblinded (range, 0 [worst] to 100 [best]). There were 26 secondary outcomes, including atrial fibrillation burden (% of time) from baseline to 12 months, measured by implantable cardiac monitors. The first 3 months were excluded from rhythm analysis.

    Results: Among 155 randomized patients (mean age, 56.1 years; 22.6% women), 97% completed the trial. Of 79 patients randomized to receive ablation, 75 underwent ablation, including 2 who crossed over to medication and 14 who underwent repeated ablation procedures. Of 76 patients randomized to receive antiarrhythmic medication, 74 received it, including 8 who crossed over to ablation and 43 for whom the first drug used failed. General Health score increased from 61.8 to 73.9 points in the ablation group vs 62.7 to 65.4 points in the medication group (between-group difference, 8.9 points; 95% CI, 3.1-14.7; P=.003). Of 26 secondary end points, 5 were analyzed; 2 were null and 2 were statistically significant, including decrease in atrial fibrillation burden (from 24.9% to 5.5% in the ablation group vs 23.3% to 11.5% in the medication group; difference -6.8%[95% CI, -12.9% to -0.7%]; P=.03). Of the Health Survey subscales, 5 of 7 improved significantly. Most common adverse events were urosepsis (5.1%) in the ablation group and atrial tachycardia (3.9%) in the medication group.

    Conclusions and relevance: Among patients with symptomatic atrial fibrillation despite use of antiarrhythmic medication, the improvement in quality of life at 12 months was greater for those treated with catheter ablation compared with antiarrhythmic medication. Although the study was limited by absence of blinding, catheter ablation may offer an advantage for quality of life.

  • 35.
    Boles, Usama
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine. Cardiology Department, Letterkenny University Hospital, Co Donegal, Ireland; Heart and Vascular centre, Cardiology Department, Mater Private Hospital, Dublin, Ireland.
    Wiklund, Urban
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Cardiology Department, Heart and Vascular Centre, Mater Private Hospital, Dublin, Ireland.
    David, Santhosh
    Ahmed, Khalid
    Henein, Michael Y.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine. Molecular and Clinical Sciences Research Institute, St George University, London, United Kingdom; Brunel University London, London, United Kingdom.
    Coronary artery ectasia carries a worse prognosis: a long-term follow-up study2019In: Polish Archives of Internal Medicine, ISSN 0032-3772, E-ISSN 1897-9483, Vol. 129, no 11, p. 833-835Article in journal (Refereed)
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  • 36.
    Boman, Kurt
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine. Research Unit, Department of Medicine, Skellefteå Hospital, Skellefteå, Sweden.
    Thormark Fröst, Finn
    Bergman, Ann-Charlotte R.
    Olofsson, Mona
    NTproBNP and ST2 as predictors for all-cause and cardiovascular mortality in elderly patients with symptoms suggestive for heart failure2018In: Biomarkers, ISSN 1354-750X, E-ISSN 1366-5804, Vol. 23, no 4, p. 373-379Article in journal (Refereed)
    Abstract [en]

    Background: A new biomarker, suppression of tumorigenicity 2 (ST2) has been introduced as a marker for fibrosis and hypertrophy. Its clinical value in comparison with N-terminal pro-hormone of brain natriuretic peptide /Amino-terminal pro-B-type natriuretic peptide (NTproBNP) in predicting mortality in elderly patients with symptoms of heart failure (HF) is still unclear.

    Aim: To evaluate the prognostic value for all-cause- and cardiovascular mortality of ST2 or NTproBNP and the combination of these biomarkers.

    Patients and methods: One hundred seventy patients patients with clinical symptoms of HF (77 (45%) were with verified HF) were recruited from one selected primary health care center (PHC) in Sweden and echocardiography was performed in all patients. Blood samples were obtained from 159 patients and stored frozen at -70 degrees C. NTproBNP was analyzed at a central core laboratory using a clinically available immunoassay. ST2 was analyzed with Critical Diagnostics Presage ST2 ELISA immunoassay.

    Results: We studied 159 patients (mean age 778.3years, 70% women). During ten years of follow up 78 patients had died, out of which 50 deaths were for cardiovascular reasons. Continuous NTproBNP and ST2 were both significantly associated with all-cause mortality (1.0001; 1.00001-1.0002, p=0.04 and 1.03; 1.003-1.06, p=0.03), NTproBNP but not ST2 remained significant for cardiovascular mortality after adjustments (1.0001; 1.00001-1.0002, p=0.03 and 1.01; 0.77-1.06, p=0.53), respectively. NTproBNP above median (>328ng/L) compared to below median was significantly associated with all-cause mortality(HR: 4.0; CI :2.46-6.61; p<0.001) and cardiovascular mortality (HR: 6.1; CI: 3.11-11.95; p<0.001). Corresponding analysis for ST2 above median (25.6ng/L) was not significantly associated neither with all-cause mortality (HR; 1.4; CI: 0.89-2.77) nor cardiovascular mortality (HR: 1.3; CI: 0.73-2.23) and no significant interaction of NTproBNP and ST2 (OR: 1.1; CI: 0.42-3.12) was found.

    Conclusion: In elderly patients with symptoms of heart failure ST2 was not superior to NTproBNP to predict all cause or cardiovascular mortality. Furthermore, it is unclear if the combination of ST2 and NTproBNP will improve long-term prognostication beyond what is achieved by NTproBNP alone.

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  • 37.
    Boström, Gustaf
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Conradsson, Mia
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Hörnsten, Carl
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Rosendahl, Erik
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Physiotherapy. Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Lindelöf, Nina
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Physiotherapy. Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Holmberg, Henrik
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Nordström, Peter
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Gustafson, Yngve
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Littbrand, Håkan
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine. Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Physiotherapy.
    Effects of a high-intensity functional exercise program on depressive symptoms among people with dementia in residential care: a randomized controlled trial2016In: International Journal of Geriatric Psychiatry, ISSN 0885-6230, E-ISSN 1099-1166, Vol. 31, no 8, p. 868-878Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: The aim of this study is to evaluate the effect of a high-intensity functional exercise program on depressive symptoms among older care facility residents with dementia.

    METHODS: Residents (n = 186) with a diagnosis of dementia, age ≥ 65 years, Mini-Mental State Examination score ≥ 10, and dependence in activities of daily living were included. Participants were randomized to a high-intensity functional exercise program or a non-exercise control activity conducted 45 min every other weekday for 4 months. The 15-item Geriatric Depression Scale (GDS) and the Montgomery-Åsberg Depression Rating Scale (MADRS) were administered by blinded assessors at baseline, 4, and 7 months.

    RESULTS: No difference between the exercise and control activity was found in GDS or MADRS score at 4 or 7 months. Among participants with GDS scores ≥ 5, reductions in GDS score were observed in the exercise and control groups at 4 months (-1.58, P = 0.001 and -1.54, P = 0.004) and 7 months (-1.25, P = 0.01 and -1.45, P = 0.007). Among participants with MADRS scores ≥ 7, a reduction in MADRS score was observed at 4 months in the control group (-2.80, P = 0.009) and at 7 months in the exercise and control groups (-3.17, P = 0.003 and -3.34, P = 0.002).

    CONCLUSIONS: A 4-month high-intensity functional exercise program has no superior effect on depressive symptoms relative to a control activity among older people with dementia living in residential care facilities. Exercise and non-exercise group activities may reduce high levels of depressive symptoms.

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  • 38. Brandsma, Joost
    et al.
    Goss, Victoria M.
    Yang, Xian
    Bakke, Per S.
    Caruso, Massimo
    Chanez, Pascal
    Dahlén, Sven-Erik
    Fowler, Stephen J.
    Horvath, Ildiko
    Krug, Norbert
    Montuschi, Paolo
    Sanak, Marek
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Shaw, Dominick E.
    Chung, Kian Fan
    Singer, Florian
    Fleming, Louise J.
    Sousa, Ana R.
    Pandis, Ioannis
    Bansal, Aruna T.
    Sterk, Peter J.
    Djukanovic, Ratko
    Postle, Anthony D.
    Lipid phenotyping of lung epithelial lining fluid in healthy human volunteers2018In: Metabolomics, ISSN 1573-3882, E-ISSN 1573-3890, Vol. 14, no 10, article id 123Article in journal (Refereed)
    Abstract [en]

    Background: Lung epithelial lining fluid (ELF)-sampled through sputum induction-is a medium rich in cells, proteins and lipids. However, despite its key role in maintaining lung function, homeostasis and defences, the composition and biology of ELF, especially in respect of lipids, remain incompletely understood.

    Objectives: To characterise the induced sputum lipidome of healthy adult individuals, and to examine associations between different ELF lipid phenotypes and the demographic characteristics within the study cohort.

    Methods: Induced sputum samples were obtained from 41 healthy non-smoking adults, and their lipid compositions analysed using a combination of untargeted shotgun and liquid chromatography mass spectrometry methods. Topological data analysis (TDA) was used to group subjects with comparable sputum lipidomes in order to identify distinct ELF phenotypes.

    Results: The induced sputum lipidome was diverse, comprising a range of different molecular classes, including at least 75 glycerophospholipids, 13 sphingolipids, 5 sterol lipids and 12 neutral glycerolipids. TDA identified two distinct phenotypes differentiated by a higher total lipid content and specific enrichments of diacyl-glycerophosphocholines, -inositols and -glycerols in one group, with enrichments of sterols, glycolipids and sphingolipids in the other. Subjects presenting the lipid-rich ELF phenotype also had significantly higher BMI, but did not differ in respect of other demographic characteristics such as age or gender.

    Conclusions: We provide the first evidence that the ELF lipidome varies significantly between healthy individuals and propose that such differences are related to weight status, highlighting the potential impact of (over)nutrition on lung lipid metabolism.

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  • 39. Bringman, S.
    et al.
    Holmberg, Henrik
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Osterberg, J.
    Location of recurrent groin hernias at TEP after Lichtenstein repair: a study based on the Swedish Hernia Register2016In: Hernia, ISSN 1265-4906, E-ISSN 1248-9204, Vol. 20, no 3, p. 387-391Article in journal (Refereed)
    Abstract [en]

    To investigate which type of hernia that has the highest risk of a recurrence after a primary Lichtenstein repair. Male patients operated on with a Lichtenstein repair for a primary direct or indirect inguinal hernia and with a TEP for a later recurrence, with both operations recorded in the Swedish Hernia Register (SHR), were included in the study. The study period was 1994-2014. Under the study period, 130,037 male patients with a primary indirect or direct inguinal hernia were operated on with a Lichtenstein repair. A second operation in the SHR was registered in 2236 of these patients (reoperation rate 1.7 %). TEP was the chosen operation in 737 in this latter cohort. The most likely location for a recurrence was the same as the primary location. If the recurrences change location from the primary place, we recognized that direct hernias had a RR of 1.51 to having a recurrent indirect hernia compared to having a direct recurrence after an indirect primary hernia repair. Recurrent hernias after Lichtenstein are more common on the same location as the primary one, compared to changing the location.

  • 40. Brinkman, Paul
    et al.
    Wagener, Ariane H.
    Hekking, Pieter-Paul
    Bansal, Aruna T.
    Maitland-van der Zee, Anke-Hilse
    Wang, Yuanyue
    Weda, Hans
    Knobel, Hugo H.
    Vink, Teunis J.
    Rattray, Nicholas J.
    D'Amico, Arnaldo
    Pennazza, Giorgio
    Santonico, Marco
    Lefaudeux, Diane
    De Meulder, Bertrand
    Auffray, Charles
    Bakke, Per S.
    Caruso, Massimo
    Chanez, Pascal
    Chung, Kian F.
    Corfield, Julie
    Dahlen, Sven-Erik
    Djukanovic, Ratko
    Geiser, Thomas
    Horvath, Ildiko
    Krug, Nobert
    Musial, Jacek
    Sun, Kai
    Riley, John H.
    Shaw, Dominic E.
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Sousa, Ana R.
    Montuschi, Paolo
    Fowler, Stephen J.
    Sterk, Peter J.
    Identification and prospective stability of electronic nose (eNose)-derived inflammatory phenotypes in patients with severe asthma2019In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 143, no 5, p. 1811-1820.e7Article in journal (Refereed)
    Abstract [en]

    Background: Severe asthma is a heterogeneous condition, as shown by independent cluster analyses based on demographic, clinical, and inflammatory characteristics. A next step is to identify molecularly driven phenotypes using “omics” technologies. Molecular fingerprints of exhaled breath are associated with inflammation and can qualify as noninvasive assessment of severe asthma phenotypes.

    Objectives: We aimed (1) to identify severe asthma phenotypes using exhaled metabolomic fingerprints obtained from a composite of electronic noses (eNoses) and (2) to assess the stability of eNose-derived phenotypes in relation to withinpatient clinical and inflammatory changes.

    Methods: In this longitudinal multicenter study exhaled breath samples were taken from an unselected subset of adults with severe asthma from the U-BIOPRED cohort. Exhaled metabolites were analyzed centrally by using an assembly of eNoses. Unsupervised Ward clustering enhanced by similarity profile analysis together with K-means clustering was performed. For internal validation, partitioning around medoids and topological data analysis were applied. Samples at 12 to 18 months of prospective follow-up were used to assess longitudinal within-patient stability.

    Results: Data were available for 78 subjects (age, 55 years [interquartile range, 45-64 years]; 41% male). Three eNosedriven clusters (n = 26/33/19) were revealed, showing differences in circulating eosinophil (P = .045) and neutrophil (P = .017) percentages and ratios of patients using oral corticosteroids (P = .035). Longitudinal within-patient cluster stability was associated with changes in sputum eosinophil percentages (P = .045).

    Conclusions: We have identified and followed up exhaled molecular phenotypes of severe asthma, which were associated with changing inflammatory profile and oral steroid use. This suggests that breath analysis can contribute to the management of severe asthma.

  • 41.
    Brunström, Mattias
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Carlberg, Bo
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Association of blood pressure lowering with mortality and cardiovascular disease across blood pressure levels: a systematic review and meta-analysis2018In: JAMA Internal Medicine, ISSN 2168-6106, E-ISSN 2168-6114, Vol. 178, no 1, p. 28-36Article in journal (Refereed)
    Abstract [en]

    Importance: High blood pressure (BP) is the most important risk factor for death and cardiovascular disease (CVD) worldwide. The optimal cutoff for treatment of high BP is debated.

    Objective: To assess the association between BP lowering treatment and death and CVD at different BP levels.

    Data sources: Previous systematic reviews were identified from PubMed, the Cochrane Database of Systematic Reviews, and the Database of Abstracts of Reviews of Effect. Reference lists of these reviews were searched for randomized clinical trials. Randomized clinical trials published after November 1, 2015, were also searched for in PubMed and the Cochrane Central Register for Controlled Trials during February 2017.

    Study selection: Randomized clinical trials with at least 1000 patient-years of follow-up, comparing BP-lowering drugs vs placebo or different BP goals were included.

    Data extraction and synthesis: Data were extracted from original publications. Risk of bias was assessed using the Cochrane Collaborations assessment tool. Relative risks (RRs) were pooled in random-effects meta-analyses with Knapp-Hartung modification. Results are reported according to PRISMA guidelines.

    Main outcomes and measures: Prespecified outcomes of interest were all-cause mortality, cardiovascular mortality, major cardiovascular events, coronary heart disease (CHD), stroke, heart failure, and end-stage renal disease.

    Results: Seventy-four unique trials, representing 306 273 unique participants (39.9% women and 60.1% men; mean age, 63.6 years) and 1.2 million person-years, were included in the meta-analyses. In primary prevention, the association of BP-lowering treatment with major cardiovascular events was dependent on baseline systolic BP (SBP). In trials with baseline SBP 160 mm Hg or above, treatment was associated with reduced risk for death (RR, 0.93; 95% CI, 0.87-1.00) and a substantial reduction of major cardiovascular events (RR, 0.78; 95% CI, 0.70-0.87). If baseline SBP ranged from 140 to 159 mm Hg, the association of treatment with mortality was similar (RR, 0.87; 95% CI, 0.75-1.00), but the association with major cardiovascular events was less pronounced (RR, 0.88; 95% CI, 0.80-0.96). In trials with baseline SBP below 140 mm Hg, treatment was not associated with mortality (RR, 0.98; 95% CI, 0.90-1.06) and major cardiovascular events (RR, 0.97; 95% CI, 0.90-1.04). In trials including people with previous CHD and mean baseline SBP of 138 mm Hg, treatment was associated with reduced risk for major cardiovascular events (RR, 0.90; 95% CI, 0.84-0.97), but was not associated with survival (RR, 0.98; 95% CI, 0.89-1.07).

    Conclusions and relevance: Primary preventive BP lowering is associated with reduced risk for death and CVD if baseline SBP is 140 mm Hg or higher. At lower BP levels, treatment is not associated with any benefit in primary prevention but might offer additional protection in patients with CHD.

  • 42.
    Brunström, Mattias
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Carlberg, Bo
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Benefits and harms of lower blood pressure treatment targets: systematic review and meta-analysis of randomised placebo-controlled trials2019In: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 9, no 9, article id e026686Article in journal (Refereed)
    Abstract [en]

    Objectives To assess the effect of antihypertensive treatment in the 130-140mm Hg systolic blood pressure range. Design Systematic review and meta-analysis. Information sources PubMed, CDSR and DARE were searched for the systematic reviews, which were manually browsed for clinical trials. PubMed and Cochrane Central Register of Controlled Trials were searched for trials directly in February 2018. Eligibility criteria Randomised double-blind trials with >= 1000 patient-years of follow-up, comparing any antihypertensive agent against placebo. Data extraction and risk of bias Two reviewers extracted study-level data, and assessed risk of bias using Cochrane Collaborations risk of bias assessment tool, independently. Main outcomes and measures Primary outcomes were all-cause mortality, major cardiovascular events and discontinuation due to adverse events. Secondary outcomes were cardiovascular mortality, myocardial infarction, stroke, heart failure, hypotension-related adverse events and renal impairment. Results Eighteen trials, including 92 567 participants (34% women, mean age 63 years), fulfilled the inclusion criteria. Primary preventive antihypertensive treatment was associated with a neutral effect on all-cause mortality (relative risk 1.00, 95% CI 0.95 to 1.06) and major cardiovascular events (1.01, 0.96 to 1.06), but an increased risk of discontinuation due to adverse events (1.23, 1.03 to 1.47). None of the secondary efficacy outcomes were significantly reduced, but the risk of hypotension-related adverse events increased with treatment (1.71, 1.32 to 2.22). In coronary artery disease secondary prevention, antihypertensive treatment was associated with reduced risk of all-cause mortality (0.91, 0.83 to 0.99) and major cardiovascular events (0.85, 0.77 to 0.94), but doubled the risk of adverse events leading to discontinuation (2.05, 1.62 to 2.61). Conclusion Primary preventive blood pressure lowering in the 130-140mm Hg systolic blood pressure range adds no cardiovascular benefit, but increases the risk of adverse events. In the secondary prevention, benefits should be weighed against harms.

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  • 43.
    Brunström, Mattias
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Carlberg, Bo
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Questionable Conclusions Regarding Blood Pressure End Points Reply2018In: JAMA Internal Medicine, ISSN 2168-6106, E-ISSN 2168-6114, Vol. 178, no 4, p. 575-576Article in journal (Refereed)
  • 44.
    Brunström, Mattias
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Carlberg, Bo
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Response to 'SPRINTin context: meta-analysis of trials with baseline normotension and lowlevels of previous cardiovascular disease' Reply2018In: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 36, no 7, p. 1603-1604Article in journal (Refereed)
  • 45.
    Brunström, Mattias
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Carlberg, Bo
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    SPRINT in context: meta-analysis of trials with baseline normotension and low levels of previous cardiovascular disease2018In: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 36, no 5, p. 979-986Article, review/survey (Refereed)
    Abstract [en]

    Objective: To estimate the effect of antihypertensive treatment in trials with baseline normotension and low levels of previous cardiovascular disease. To test if the results from SPRINT are compatible with those from other trials, and test the impact of SPRINT results on overall effect estimates. Methods: Systematic review and meta-analysis of randomized controlled trials with at least 1000 patient-years of follow-up, comparing antihypertensive treatment versus placebo, or different blood pressure goals against each other. Trials with at least 50% previous cardiovascular disease were excluded. Results: Sixteen trials, including 66816 participants, were included in the meta-analyses. Mean baseline SBP was 138mmHg, and mean difference between treatment arms was 5.5mmHg. Antihypertensive treatment was associated with a neutral effect on all-cause mortality [relative risk 0.98, 95% confidence interval (CI) 0.92-1.05] and major cardiovascular events (0.97, 0.91-1.03). Results from SPRINT differed significantly from those of other trials (P=0.012 for all-cause mortality; P=0.016 for major cardiovascular events), but overall effect estimates were similar when SPRINT was excluded (1.01, 0.95-1.06 for all-cause mortality; 0.98, 0.93-1.03 for major cardiovascular events). Treatment was associated with reduced risk of secondary outcomes stroke (0.84, 0.71-1.00) and heart failure (0.88, 0.78-0.98), although heterogeneity was high in the stroke analysis (I-2=54%). Conclusion: SPRINT results are not representative for trials with baseline normotension and low levels of previous cardiovascular disease. Antihypertensive treatment does not protect against death or major cardiovascular events in this setting.

  • 46.
    Brunström, Mattias
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Carlberg, Bo
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Standardization according to blood pressure lowering in meta-analyses of antihypertensive trials: comparison of three methodological approaches2018In: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 36, no 1, p. 4-15Article, review/survey (Refereed)
    Abstract [en]

    OBJECTIVE: Assess how standardization of relative risks (RRs) and standard errors (SEs), according to blood pressure differences within trials, affects heterogeneity, overall effect estimates and study weights in meta-analyses of antihypertensive treatment.

    METHOD: Data from a previous systematic review were used. Three sets of analyses were performed, using both random-effects and fixed-effects model for meta-analyses. First, we used raw data from the included trials. Second, we standardized RRs as if SBP was reduced by 10 mmHg in all trials. Third, we standardized both RRs and SEs.

    RESULTS: When RRs were standardized according to blood pressure lowering, heterogeneity between trials increased (I = 36 vs. 93% for mortality). This conferred large differences in treatment effect estimates using random-effects and fixed-effects model (RR 0.79, 95% confidence interval 0.70-0.89, respectively, 0.97, 0.94-0.99). When SEs were standardized, confidence intervals for individual trials widened, resulting in lower power to detect heterogeneity across trials. Study weights were dissociated from number of events in trials (P < 0.0001, R = 0.99 before standardization vs. P = 0.063, R = 0.05 after standardization). This induced a secondary shift in weight from trials with lower baseline SBP to trials with higher baseline SBP, resulting in exaggerated overall effect estimates.

    CONCLUSION: Standardization of RRs exaggerates differences between trials and makes meta-analyses highly sensitive to choice of statistical method. Standardization of SEs masks heterogeneity and results in biased effect estimates.

  • 47.
    Bråndal, Anna
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Physiotherapy. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Eriksson, Marie
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Glader, Eva-Lotta
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Wester, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine. Department of Clinical Sciences, Karolinska Institute, Danderyd hospital, Stockholm, Sweden.
    Effect of early supported discharge after stroke on patient reported outcome based on the Swedish Riksstroke registry2019In: BMC Neurology, ISSN 1471-2377, E-ISSN 1471-2377, Vol. 19, article id 40Article in journal (Refereed)
    Abstract [en]

    Background: The efficacy of early supported discharge (ESD) has not been tested in current stroke care setting, which provide relatively short hospital stays, access to hyper-acute therapies and early carotid stenosis interventions. This study aimed to compare patient-reported outcome measures (PROM) among patients with stroke that received modern stroke unit care with or without ESD.

    Methods: Observational study of 30,232 patients with first-ever stroke registered in the Riksstroke registry in Sweden, between 1 January 2010 and 31 December 2013. Patient characteristics were collected from the Riksstroke and Statistics Sweden databases. The primary outcome was satisfaction with the rehabilitation at 3 months after discharge. Secondary outcome were information about stroke provided, tiredness/fatigue, pain, dysthymia/ depression, general health status and dependence in activities of daily living (mobility, toileting and dressing) at 3 months after the stroke. We used separate multivariable logistic regression models for each PROM variable to analyze associations between PROMs and ESD/no ESD.

    Results: The ESD group comprised 1495 participants: the control group comprised 28,737 participants. Multivariable logistic regression models of PROMs showed that, compared to controls, the ESD group was more satisfied with rehabilitation after discharge (OR: 1.78, 95% CI: 1.17–2.49), experienced less dysthymia/depression (OR: 0.68, 95% 0.55–0.84) and showed more independence in mobility (OR: 1.50, 95% CI: 1.17–1.92), toileting (OR: 1.30, 95%CI: 1.05–1.61), and dressing (OR: 1.23, 95%CI: 1.02–1.48).

    Conclusion: In the setting of modern stroke unit care, ESD appeared to have positive effects on stroke rehabilitation, in the subacute phase.

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  • 48.
    Bugaytsova, Jeanna A.
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Björnham, Oscar
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics. Swedish Defence Research Agency, 906 21 Umeå, Sweden.
    Chernov, Yevgen A.
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Gideonsson, Pär
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Henriksson, Sara
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Mendez, Melissa
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Sjöström, Rolf
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Mahdavi, Jafar
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics. School of Life Sciences, CBS, University of Nottingham, NG7 2RD Nottingham, UK.
    Shevtsova, Anna
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Ilver, Dag
    Moonens, Kristof
    Quintana-Hayashi, Macarena P.
    Moskalenko, Roman
    Aisenbrey, Christopher
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Bylund, Göran
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Schmidt, Alexej
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics. Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Åberg, Anna
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Brännström, Kristoffer
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Koeniger, Verena
    Vikström, Susanne
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Rakhimova, Lena
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics. Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Hofer, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Ögren, Johan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Liu, Hui
    Goldman, Matthew D.
    Whitmire, Jeannette M.
    Åden, Jörgen
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Younson, Justine
    Kelly, Charles G.
    Gilman, Robert H.
    Chowdhury, Abhijit
    Mukhopadhyay, Asish K.
    Nair, G. Balakrish
    Papadakos, Konstantinos S.
    Martinez-Gonzalez, Beatriz
    Sgouras, Dionyssios N.
    Engstrand, Lars
    Unemo, Magnus
    Danielsson, Dan
    Suerbaum, Sebastian
    Oscarson, Stefan
    Morozova-Roche, Ludmilla A.
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Olofsson, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Gröbner, Gerhard
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Holgersson, Jan
    Esberg, Anders
    Umeå University, Faculty of Medicine, Department of Odontology.
    Strömberg, Nicklas
    Umeå University, Faculty of Medicine, Department of Odontology.
    Landström, Maréne
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Eldridge, Angela M.
    Chromy, Brett A.
    Hansen, Lori M.
    Solnick, Jay V.
    Linden, Sara K.
    Haas, Rainer
    Dubois, Andre
    Merrell, D. Scott
    Schedin, Staffan
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics.
    Remaut, Han
    Arnqvist, Anna
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Berg, Douglas E.
    Boren, Thomas
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Helicobacter pylori Adapts to Chronic Infection and Gastric Disease via pH-Responsive BabA-Mediated Adherence2017In: Cell Host and Microbe, ISSN 1931-3128, E-ISSN 1934-6069, Vol. 21, no 3, p. 376-389Article in journal (Refereed)
    Abstract [en]

    The BabA adhesin mediates high-affinity binding of Helicobacter pylori to the ABO blood group antigen-glycosylated gastric mucosa. Here we show that BabA is acid responsive-binding is reduced at low pH and restored by acid neutralization. Acid responsiveness differs among strains; often correlates with different intragastric regions and evolves during chronic infection and disease progression; and depends on pH sensor sequences in BabA and on pH reversible formation of high-affinity binding BabA multimers. We propose that BabA's extraordinary reversible acid responsiveness enables tight mucosal bacterial adherence while also allowing an effective escape from epithelial cells and mucus that are shed into the acidic bactericidal lumen and that bio-selection and changes in BabA binding properties through mutation and recombination with babA-related genes are selected by differences among individuals and by changes in gastric acidity over time. These processes generate diverse H. pylori subpopulations, in which BabA's adaptive evolution contributes to H. pylori persistence and overt gastric disease.

  • 49.
    Bytyci, I. Ibadete
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Bajraktari, G.
    Henein, Mark
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Increased left atrial volume predicts atrial fibrillation recurrence after transcatheter ablation: a systematic review and meta-analysis2017In: European Journal of Heart Failure, ISSN 1388-9842, E-ISSN 1879-0844, Vol. 19, no Suppl: 1, p. 252-252Article in journal (Refereed)
  • 50.
    Bytyci, I. Ibadete
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Bajraktari, G.
    Henein, Mark
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Left atrial size as predictor of recurrences after catheter ablation in paroxysmal atrial fibrillation: a systematic review and meta-analysis2017In: European Journal of Heart Failure, ISSN 1388-9842, E-ISSN 1879-0844, Vol. 19, no S1, p. 80-80, article id P360Article in journal (Refereed)
    Abstract [en]

    Background and Aim: Left atrial (LA) enlargement is associated with paroxysmal atrial fibrillation (PAF) incidence and outcome. The predictive role of the LA size in AF treatment with catheter ablation is still controversial. The aim of this meta-analysis was to analyze the potential association between LA diameter in patients with PAF undergoing ablation and AF recurrence after ablation.

    Methods: We systematically searched PubMed-Medline, EMBASE, Scopus, Google Scholar and the Cochrane Central Registry, up to December 2016 in order to select clinical trial and observational studies, which assessed the predictive role of LA diameter in AF recurrence after catheter-ablation. 2962 patients from 16 studies with paroxysmal AF (PAF) were included.

    Results: The pooled analysis showed that after a follow-up period of 19. 66± 8.31 months, patients with AF recurrence had larger LA size compared with those without AF recurrence, with a weighted mean difference (WMD) 2.31 ([95% CI 1.27 to 3.34], P < 0.0001). LA diameter ≥40 mm predicted AF recurrence HR:1.04 [95% CI 1.00 to 1.08], P=0.04), but the best cut-off value, in all included patients, was ≥50mm HR:3.08 [95% CI 1.47 to 6.49], P=0.003).

    Conclusions: Enlarged left atrium in patients with PAF undergoing catheter ablation predicts recurrences. The diameter more than 50 mm is the best cut-off of the recurrences of AF, but diameter of 40 mm also can predict recurrences in these patients.

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