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  • 1. 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)
  • 2. 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.

  • 3. 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.

  • 4.
    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.

  • 5.
    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.

  • 6.
    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.

  • 7.
    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.

  • 8.
    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
    Eriksson, Berne
    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.

  • 9. 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.

  • 10.
    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.

  • 11. 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.

  • 12. 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. 

  • 13. 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.

  • 14.
    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.

  • 15.
    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.

  • 16.
    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.

  • 17.
    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.

  • 18. 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.

  • 19. 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.

  • 20. 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.

  • 21.
    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.

  • 22.
    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)
  • 23.
    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)
  • 24.
    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.

  • 25.
    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.

  • 26.
    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.
    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.
    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.
    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.

  • 27. Chen, Yan
    et al.
    Estampador, Angela C
    Keller, Maria
    Poveda, Alaitz
    Dalla-Riva, Jonathan
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Biobank Research.
    Renström, Frida
    Umeå University, Faculty of Medicine, Department of Biobank Research. Genetic and Molecular Epidemiology Unit, Department of Clinical Sciences, Lund University, Skåne University Hospital Malmö, Malmö, Sweden.
    Kurbasic, Azra
    Franks, Paul W.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine. Genetic and Molecular Epidemiology Unit, Department of Clinical Sciences, Lund University, Skåne University Hospital Malmö, Malmö, Sweden; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston MA, USA.
    Varga, Tibor V
    The combined effects of FADS gene variation and dietary fats in obesity-related traits in a population from the far north of Sweden: the GLACIER Study2019In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 43, no 4, p. 808-820Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Recent analyses in Greenlandic Inuit identified six genetic polymorphisms (rs74771917, rs3168072, rs12577276, rs7115739, rs174602 and rs174570) in the fatty acid desaturase gene cluster (FADS1-FADS2-FADS3) that are associated with multiple metabolic and anthropometric traits. Our objectives were to systematically assess whether dietary polyunsaturated fatty acid (PUFA) intake modifies the associations between genetic variants in the FADS gene cluster and cardiometabolic traits, and to functionally annotate top-ranking candidates to estimate their regulatory potential.

    METHODS: Data analyses consisted of the following: interaction analyses between the 6 candidate genetic variants and dietary PUFA intake; gene-centric joint analyses to detect interaction signals in the FADS region; haplotype-centric joint tests across 30 haplotype blocks in the FADS region to refine interaction signals; and functional annotation of top-ranking loci from the previous steps. These analyses were undertaken in Swedish adults from the GLACIER Study (N = 5,160); data on genetic variation and eight cardiometabolic traits were used.

    RESULTS: Interactions were observed between rs174570 and n-6 PUFA intake on fasting glucose (Pint = 0.005) and between rs174602 and n-3 PUFA intake on total cholesterol (Pint = 0.001). Gene-centric analyses demonstrated a statistically significant interaction effect for FADS and n-3 PUFA on triglycerides (Pint = 0.005) considering genetic main effects as random. Haplotype analyses revealed three blocks (Pint < 0.011) that could drive the interaction between FADS and n-3 PUFA on triglycerides; functional annotation of these regions showed that each block harbours a number of highly functional regulatory variants; FADS2 rs5792235 demonstrated the highest functionality score.

    CONCLUSIONS: The association between FADS variants and triglycerides may be modified by PUFA intake. The intronic FADS2 rs5792235 variant is a potential causal variant in the region, having the highest regulatory potential. However, our results suggest that multiple haplotypes may harbour functional variants in a region, rather than a single causal variant.

  • 28. Dalin, Frida
    et al.
    Nordling Eriksson, Gabriel
    Dahlqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Hallgren, Åsa
    Wahlberg, Jeanette
    Ekwall, Olov
    Söderberg, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Rönnelid, Johan
    Olcén, Per
    Winqvist, Ola
    Catrina, Sergiu-Bogdan
    Kriström, Berit
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Laudius, Maria
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Isaksson, Magnus
    Halldin Stenlid, Maria
    Gustafsson, Jan
    Gebre-Medhin, Gennet
    Björnsdottir, Sigridur
    Janson, Annika
    Åkerman, Anna-Karin
    Åman, Jan
    Duchen, Karel
    Bergthorsdottir, Ragnhildur
    Johannsson, Gudmundur
    Lindskog, Emma
    Landin-Olsson, Mona
    Elfving, Maria
    Waldenström, Erik
    Hulting, Anna-Lena
    Kämpe, Olle
    Bensing, Sophie
    Clinical and immunological characteristics of Autoimmune Addison's disease: a nationwide Swedish multicenter study2017In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 102, no 2, p. 379-389Article in journal (Refereed)
    Abstract [en]

    CONTEXT: Studies on clinical and immunological features of Autoimmune Addison's disease (AAD) are needed to understand the disease burden and increased mortality.

    OBJECTIVE: To provide upgraded data on autoimmune comorbidities, replacement therapy, autoantibody profiles and cardiovascular risk factors.

    DESIGN, SETTING AND PARTICIPANTS: Cross sectional, population-based study. 660 AAD patients were included utilizing the Swedish Addison Registry (SAR) 2008-2014. When analyzing cardiovascular risk factors, 3,594 individuals from the population-based survey in Northern Sweden, MONICA (MONItoring of Trends and Determinants of CArdiovascular Disease), served as controls.

    MAIN OUTCOME MEASURE: Prevalence of autoimmune comorbidities and cardiovascular risk factors. Autoantibodies against 13 autoantigens were determined.

    RESULTS: Sixty percent of the SAR cohort consisted of females. Mean age at diagnosis was significantly higher for females than for males (36.8 vs. 31.1 years). The proportion of 21-hydroxylase autoantibody positive patients was 83% and 62% of patients had one or more associated autoimmune diseases, more frequently coexisting in females (p<0.0001). AAD patients had lower BMI (p<0.0001) and prevalence of hypertension (p=0.027) compared with controls. Conventional hydrocortisone tablets were used by 89% of patients; with the mean dose 28.1±8.5 mg/day. The mean hydrocortisone equivalent dose normalized to body surface was 14.8±4.4 mg/m(2)/day. Higher hydrocortisone equivalent dose was associated with higher incidence of hypertension (p=0.046).

    CONCLUSIONS: Careful monitoring of AAD patients is warranted to detect associated autoimmune diseases. Contemporary Swedish AAD patients do not have increased prevalence of overweight, hypertension, T2DM or hyperlipidemia. However, high glucocorticoid replacement doses may be a risk factor for hypertension.

  • 29.
    Danielsson, Nora
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Understanding the epidemiology and basic characteristics of hereditary transthyretin amyloidosis in Sweden2018Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 30.
    Darehed, David
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Blom, Mathias
    Glader, Eva-Lotta
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Niklasson, Johan
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Norrving, Bo
    Bray, Benjamin D.
    Eriksson, Marie
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Diurnal variations in the quality of stroke care in Sweden2019In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 140, no 2, p. 123-130Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: A recent study of acute stroke patients in England and Wales revealed several patterns of temporal variation in quality of care. We hypothesized that similar patterns would be present in Sweden and aimed to describe these patterns. Additionally, we aimed to investigate whether hospital type conferred resilience against temporal variation.

    MATERIALS & METHODS: We conducted this nationwide registry-based study using data from the Swedish Stroke Register (Riksstroke) including all adult patients registered with acute stroke between 2011 and 2015. Outcomes included process measures and survival. We modeled time of presentation as on/off hours, shifts, day of week, 4h and 12 h time blocks. We studied hospital resilience by comparing outcomes across hospital types.

    RESULTS: 113862 stroke events in 72 hospitals were included. The process indicators and survival all showed significant temporal variation. Door-to-needle (DTN) time within 30 minutes was less likely during nighttime than daytime (OR 0.50; 95% CI 0.41-0.60). Patients admitted during off-hours had lower odds of direct stroke unit (SU) admission (OR 0.72; 95% CI 0.70-0.75). 30-day survival was lower in nighttime versus daytime presentations (OR 0.90, 95% CI 0.84-0.96). The effects of temporal variation differed significantly between hospital types for DTN time within 30 minutes and direct SU admission where university hospitals were more resilient than specialized non-university hospitals.

    CONCLUSIONS: Our study shows that variation in quality of care and survival is present throughout the whole week. We also found that university hospitals were more resilient to temporal variation than specialized non-university hospitals.

  • 31.
    Darehed, David
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine. 1 Department of Medicine, Ga¨llivare Hospital, Sweden.
    Norrving, Bo
    Stegmayr, Birgitta
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Zingmark, Karin
    Blom, Mathias C.
    Patients with acute stroke are less likely to be admitted directly to a stroke unit when hospital beds are scarce: a Swedish multicenter register study2017In: European Stroke Journal, ISSN 2396-9873, E-ISSN 2396-9881, Vol. 2, no 2, p. 178-186Article in journal (Refereed)
    Abstract [en]

    Introduction: It is well established that managing patients with acute stroke in dedicated stroke units is associated with improved functioning and survival. The objectives of this study are to investigate whether patients with acute stroke are less likely to be directly admitted to a stroke unit from the Emergency Department when hospital beds are scarce and to measure variation across hospitals in terms of this outcome.

    Patients and methods: This register study comprised data on patients with acute stroke admitted to 14 out of 72 Swedish hospitals in 2011-2014. Data from the Swedish stroke register were linked to administrative daily data on hospital bed occupancy (measured at 6 a.m.). Logistic regression analysis was used to analyse the association between bed occupancy and direct stroke unit admission.

    Results: A total of 13,955 hospital admissions were included; 79.6% were directly admitted to a stroke unit from the Emergency Department. Each percentage increase in hospital bed occupancy was associated with a 1.5% decrease in odds of direct admission to a stroke unit (odds ratio = 0.985, 95% confidence interval = 0.978-0.992). The best-performing hospital exhibited an odds ratio of 3.8 (95% confidence interval = 2.6-5.5) for direct admission to a stroke unit versus the reference hospital.

    Discussion and conclusion: We found an association between hospital crowding and reduced quality of care in acute stroke, portrayed by a lower likelihood of patients being directly admitted to a stroke unit from the Emergency Department. The magnitude of the effect varied considerably across hospitals.

  • 32.
    Davila-Seijo, P.
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine. Academia Espanola de Dermatologıa Venereolog Fundacion Piel Sana, Madrid, Spain.
    Descalzo, M. A.
    Registries as real-world cohort studies that are useful and necessary in the pyramid of evidence2018In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 178, no 1, p. 300-301Article in journal (Refereed)
  • 33. de Vries, Paul S.
    et al.
    Brown, Michael R.
    Bentley, Amy R.
    Sung, Yun J.
    Winkler, Thomas W.
    Ntalla, Ioanna
    Schwander, Karen
    Kraja, Aldi T.
    Guo, Xiuqing
    Franceschini, Nora
    Cheng, Ching-Yu
    Sim, Xueling
    Vojinovic, Dina
    Huffman, Jennifer E.
    Musani, Solomon K.
    Li, Changwei
    Feitosa, Mary F.
    Richard, Melissa A.
    Noordam, Raymond
    Aschard, Hugues
    Bartz, Traci M.
    Bielak, Lawrence F.
    Deng, Xuan
    Dorajoo, Rajkumar
    Lohman, Kurt K.
    Manning, Alisa K.
    Rankinen, Tuomo
    Smith, Albert V.
    Tajuddin, Salman M.
    Evangelou, Evangelos
    Graff, Mariaelisa
    Alver, Maris
    Boissel, Mathilde
    Chai, Jin Fang
    Chen, Xu
    Divers, Jasmin
    Gandin, Ilaria
    Gao, Chuan
    Goel, Anuj
    Hagemeijer, Yanick
    Harris, Sarah E.
    Hartwig, Fernando P.
    He, Meian
    Horimoto, Andrea R. V. R.
    Hsu, Fang-Chi
    Jackson, Anne U.
    Kasturiratne, Anuradhani
    Komulainen, Pirjo
    Kuehnel, Brigitte
    Laguzzi, Federica
    Lee, Joseph H.
    Luan, Jian'an
    Lyytikainen, Leo-Pekka
    Matoba, Nana
    Nolte, Ilja M.
    Pietzner, Maik
    Riaz, Muhammad
    Said, M. Abdullah
    Scott, Robert A.
    Sofer, Tamar
    Stancakova, Alena
    Takeuchi, Fumihiko
    Tayo, Bamidele O.
    van der Most, Peter J.
    Varga, Tibor V.
    Wang, Yajuan
    Ware, Erin B.
    Wen, Wanqing
    Yanek, Lisa R.
    Zhang, Weihua
    Zhao, Jing Hua
    Afaq, Saima
    Amin, Najaf
    Amini, Marzyeh
    Arking, Dan E.
    Aung, Tin
    Ballantyne, Christie
    Boerwinkle, Eric
    Broeckel, Ulrich
    Campbell, Archie
    Canouil, Mickael
    Charumathi, Sabanayagam
    Chen, Yii-Der Ida
    Connell, John M.
    de Faire, Ulf
    de las Fuentes, Lisa
    de Mutsert, Renee
    de Silva, H. Janaka
    Ding, Jingzhong
    Dominiczak, Anna F.
    Duan, Qing
    Eaton, Charles B.
    Eppinga, Ruben N.
    Faul, Jessica D.
    Fisher, Virginia
    Forrester, Terrence
    Franco, Oscar H.
    Friedlander, Yechiel
    Ghanbari, Mohsen
    Giulianini, Franco
    Grabe, Hans J.
    Grove, Megan L.
    Gu, C. Charles
    Harris, Tamara B.
    Heikkinen, Sami
    Heng, Chew-Kiat
    Hirata, Makoto
    Hixson, James E.
    Howard, Barbara V.
    Ikram, M. Arfan
    Jacobs, David R., Jr.
    Johnson, Craig
    Jonas, Jost Bruno
    Kammerer, Candace M.
    Katsuya, Tomohiro
    Khor, Chiea Chuen
    Kilpelainen, Tuomas O.
    Koh, Woon-Puay
    Koistinen, Heikki A.
    Kolcic, Ivana
    Kooperberg, Charles
    Krieger, Jose E.
    Kritchevsky, Steve B.
    Kubo, Michiaki
    Kuusisto, Johanna
    Lakka, Timo A.
    Langefeld, Carl D.
    Langenberg, Claudia
    Launer, Lenore J.
    Lehne, Benjamin
    Lemaitre, Rozenn N.
    Li, Yize
    Liang, Jingjing
    Liu, Jianjun
    Liu, Kiang
    Loh, Marie
    Louie, Tin
    Magi, Reedik
    Manichaikul, Ani W.
    McKenzie, Colin A.
    Meitinger, Thomas
    Metspalu, Andres
    Milaneschi, Yuri
    Milani, Lili
    Mohlke, Karen L.
    Mosley, Thomas H., Jr.
    Mukamal, Kenneth J.
    Nalls, Mike A.
    Nauck, Matthias
    Nelson, Christopher P.
    Sotoodehnia, Nona
    O'Connell, Jeff R.
    Palmer, Nicholette D.
    Pazoki, Raha
    Pedersen, Nancy L.
    Peters, Annette
    Peyser, Patricia A.
    Polasek, Ozren
    Poulter, Neil
    Raffel, Leslie J.
    Raitakari, Olli T.
    Reiner, Alex P.
    Rice, Treva K.
    Rich, Stephen S.
    Robino, Antonietta
    Robinson, Jennifer G.
    Rose, Lynda M.
    Rudan, Igor
    Schmidt, Carsten O.
    Schreiner, Pamela J.
    Scott, William R.
    Sever, Peter
    Shi, Yuan
    Sidney, Stephen
    Sims, Mario
    Smith, Blair H.
    Smith, Jennifer A.
    Snieder, Harold
    Starr, John M.
    Strauch, Konstantin
    Tan, Nicholas
    Taylor, Kent D.
    Teo, Yik Ying
    Tham, Yih Chung
    Uitterlinden, Andre G.
    van Heemst, Diana
    Vuckovic, Dragana
    Waldenberger, Melanie
    Wang, Lihua
    Wang, Yujie
    Wang, Zhe
    Wei, Wen Bin
    Williams, Christine
    Wilson, Gregory, Sr.
    Wojczynski, Mary K.
    Yao, Jie
    Yu, Bing
    Yu, Caizheng
    Yuan, Jian-Min
    Zhao, Wei
    Zonderman, Alan B.
    Becker, Diane M.
    Boehnke, Michael
    Bowden, Donald W.
    Chambers, John C.
    Deary, Ian J.
    Esko, Tonu
    Farrall, Martin
    Franks, Paul W.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine. Department of Nutrition, T. H. Chan School of Public Health, Harvard University, Boston, Massachusetts; Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University Diabetes Centre, Skåne University Hospital, Malmö, Sweden; Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, Medical Sciences Division, University of Oxford, Oxford, United Kingdom.
    Freedman, Barry I.
    Froguel, Philippe
    Gasparini, Paolo
    Gieger, Christian
    Horta, Bernardo L.
    Kamatani, Yoichiro
    Kato, Norihiro
    Kooner, Jaspal S.
    Laakso, Markku
    Leander, Karin
    Lehtimaki, Terho
    Magnusson, Patrik K. E.
    Penninx, Brenda
    Pereira, Alexandre C.
    Rauramaa, Rainer
    Samani, Nilesh J.
    Scott, James
    Shu, Xiao-Ou
    van der Harst, Pim
    Wagenknecht, Lynne E.
    Wang, Ya Xing
    Wareham, Nicholas J.
    Watkins, Hugh
    Weir, David R.
    Wickremasinghe, Ananda R.
    Zheng, Wei
    Elliott, Paul
    North, Kari E.
    Bouchard, Claude
    Evans, Michele K.
    Gudnason, Vilmundur
    Liu, Ching-Ti
    Liu, Yongmei
    Psaty, Bruce M.
    Ridker, Paul M.
    van Dam, Rob M.
    Kardia, Sharon L. R.
    Zhu, Xiaofeng
    Rotimi, Charles N.
    Mook-Kanamori, Dennis O.
    Fornage, Myriam
    Kelly, Tanika N.
    Fox, Ervin R.
    Hayward, Caroline
    van Duijn, Cornelia M.
    Tai, E. Shyong
    Wong, Tien Yin
    Liu, Jingmin
    Rotter, Jerome I.
    Gauderman, W. James
    Province, Michael A.
    Munroe, Patricia B.
    Rice, Kenneth
    Chasman, Daniel I.
    Cupples, L. Adrienne
    Rao, Dabeeru C.
    Morrison, Alanna C.
    Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions2019In: American Journal of Epidemiology, ISSN 0002-9262, E-ISSN 1476-6256, Vol. 188, no 6, p. 1033-1054Article in journal (Refereed)
    Abstract [en]

    A person's lipid profile is influenced by genetic variants and alcohol consumption, but the contribution of interactions between these exposures has not been studied. We therefore incorporated gene-alcohol interactions into a multiancestry genome-wide association study of levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. We included 45 studies in stage 1 (genome-wide discovery) and 66 studies in stage 2 (focused follow-up), for a total of 394,584 individuals from 5 ancestry groups. Analyses covered the period July 2014-November 2017. Genetic main effects and interaction effects were jointly assessed by means of a 2-degrees-of-freedom (df) test, and a 1-df test was used to assess the interaction effects alone. Variants at 495 loci were at least suggestively associated (P < 1 x 10(-6)) with lipid levels in stage 1 and were evaluated in stage 2, followed by combined analyses of stage 1 and stage 2. In the combined analysis of stages 1 and 2, a total of 147 independent loci were associated with lipid levels at P < 5 x 10(-8) using 2-df tests, of which 18 were novel. No genome-wide-significant associations were found testing the interaction effect alone. The novel loci included several genes (proprotein convertase subtilisin/kexin type 5 (PCSK5), vascular endothelial growth factor B (VEGFB), and apolipoprotein B mRNA editing enzyme, catalytic polypeptide 1 (APOBEC1) complementation factor (A1CF)) that have a putative role in lipid metabolism on the basis of existing evidence from cellular and experimental models.

  • 34. Donnelly, Louise A.
    et al.
    Zhou, Kaixin
    Doney, Alex S. F.
    Jennison, Chris
    Franks, Paul W.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine. Department of Clinical Science, Genetic and Molecular Epidemiology Unit, Lund University, Malmö, Sweden; Department of Nutrition, Harvard School of Public Health, Boston, USA.
    Pearson, Ewan R.
    Rates of glycaemic deterioration in a real-world population with type 2 diabetes2018In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 61, no 3, p. 607-615Article in journal (Refereed)
    Abstract [en]

    Aims/hypothesis: There is considerable variability in how diabetes progresses after diagnosis. Progression modelling has largely focused on 'time to failure' methods, yet determining a 'coefficient of failure' has many advantages. We derived a rate of glycaemic deterioration in type 2 diabetes, using a large real-world cohort, and aimed to investigate the clinical, biochemical, pharmacological and immunological variables associated with fast and slow rates of glycaemic deterioration. Methods: An observational cohort study was performed using the electronic medical records from participants in the Genetics of Diabetes Audit and Research in Tayside Study (GoDARTS). A model was derived based on an individual's observed HbA(1c) measures from the first eligible HbA(1c) after the diagnosis of diabetes through to the study end (defined as insulin initiation, death, leaving the area or end of follow-up). Each HbA(1c) measure was time-dependently adjusted for the effects of non-insulin glucose-lowering drugs, changes in BMI and corticosteroid use. GAD antibody (GADA) positivity was defined as GAD titres above the 97.5th centile of the population distribution. Results: The mean (95% CI) glycaemic deterioration for type 2 diabetes and GADA-positive individuals was 1.4 (1.3, 1.4) and 2.8 (2.4, 3.3) mmol/mol HbA(1c) per year, respectively. A younger age of diagnosis, lower HDL-cholesterol concentration, higher BMI and earlier calendar year of diabetes diagnosis were independently associated with higher rates of glycaemic deterioration in individuals with type 2 diabetes. The rate of deterioration in those diagnosed at over 70 years of age was very low, with 66% having a rate of deterioration of less than 1.1 mmol/mol HbA(1c) per year, and only 1.5% progressing more rapidly than 4.4 mmol/mol HbA(1c) per year. Conclusions/interpretation: We have developed a novel approach for modelling the progression of diabetes in observational data across multiple drug combinations. This approach highlights how glycaemic deterioration in those diagnosed at over 70 years of age is minimal, supporting a stratified approach to diabetes management.

  • 35. Efe, Cumali
    et al.
    Al Taii, Haider
    Ytting, Henriette
    Aehling, Niklas
    Bhanji, Rahima A.
    Hagstrom, Hannes
    Purnak, Tugrul
    Muratori, Luigi
    Werner, Mårten
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Muratori, Paolo
    Klintman, Daniel
    Schiano, Thomas D.
    Montano-Loza, Aldo J.
    Berg, Thomas
    Larsen, Fin Stolze
    Alkhouri, Naim
    Ozaslan, Ersan
    Heneghan, Michael A.
    Yoshida, Eric M.
    Wahlin, Staffan
    Tacrolimus and Mycophenolate Mofetil as Second-Line Therapies for Pediatric Patients with Autoimmune Hepatitis2018In: Digestive Diseases and Sciences, ISSN 0163-2116, E-ISSN 1573-2568, Vol. 63, no 5, p. 1348-1354Article in journal (Refereed)
    Abstract [en]

    We studied the efficacy and safety of mycophenolate mofetil (MMF) and tacrolimus as second-line therapy in pediatric patients with autoimmune hepatitis (AIH) who were intolerant or non-responders to standard therapy (corticosteroid and azathioprine). We performed a retrospective study of data from 13 centers in Europe, USA, and Canada. Thirty-eight patients (< 18 years old) who received second-line therapy (18 MMF and 20 tacrolimus), for a median of 72 months (range 8-182) were evaluated. Patients were categorized into two groups: Group 1 (n = 17) were intolerant to corticosteroid or azathioprine, and group 2 (n = 21) were non-responders to standard therapy. Overall complete response rates were similar in patients treated with MMF and tacrolimus (55.6 vs. 65%, p = 0.552). In group 1, MMF and tacrolimus maintained a biochemical remission in 88.9 and 87.5% of patients, respectively (p = 0.929). More patients in group 2 given tacrolimus compared to MMF had a complete response, but the difference was not statistically significant (50.0 vs. 22.2%, p = 0.195). Biochemical remission was achieved in 71.1% (27/38) of patients by tacrolimus and/or MMF. Decompensated cirrhosis was more commonly seen in MMF and/or tacrolimus non-responders than in responders (45.5 vs. 7.4%, p = 0.006). Five patients who received second-line therapy (2 MMF and 3 tacrolimus) developed side effects that led to therapy withdrawal. Long-term therapy with MMF or tacrolimus was generally well tolerated by pediatric patients with AIH. Both MMF and tacrolimus had excellent efficacy in patients intolerant to corticosteroid or azathioprine. Tacrolimus might be more effective than MMF in patients failing previous therapy.

  • 36. Ehret, Georg B.
    et al.
    Ferreira, Teresa
    Chasman, Daniel I.
    Jackson, Anne U.
    Schmidt, Ellen M.
    Johnson, Toby
    Thorleifsson, Gudmar
    Luan, Jian'an
    Donnelly, Louise A.
    Kanoni, Stavroula
    Petersen, Ann -Kristin
    Pihurl, Vasyl
    Strawbridge, Rona J.
    Shungin, Dmitry
    Umeå University, Faculty of Medicine, Department of Odontology. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine. Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Malmö, Sweden.
    Hughes, Maria F.
    Meirelles, Osorio
    Kaakinen, Marika
    Bouatia-Naji, Nabila
    Kristiansson, Kati
    Shah, Sonia
    Kleber, Marcus E.
    Guo, Xiuqing
    Lyytikainen, Leo-Pekka
    Fava, Cristiano
    Eriksson, Nidas
    Nolte, Ilja M.
    Magnusson, Patrik K.
    Salfati, Elias L.
    Rallidis, Loukianos S.
    Theusch, Elizabeth
    Smith, Andrew J. P.
    Folkersen, Lasse
    Witkowska, Kate
    Pers, Tune H.
    Joehanes, Roby
    Kim, Stuart K.
    Lataniotis, Lazaros
    Jansen, Rick
    Johnson, Andrew D.
    Warren, Helen
    Kim, Young Jin
    Zhao, Wei
    Wu, Ying
    Tayo, Bamidele O.
    Bochud, Murielle
    Absher, Devin
    Adair, Linda S.
    Amin, Najaf
    Arkingl, Dan E.
    Axelsson, Tomas
    Baldassarre, Damian
    Balkau, Beverley
    Bandinelli, Stefania
    Barnes, Michael R.
    Barroso, Ines
    Bevan, Stephen
    Bis, Joshua C.
    Bjornsdottir, Gyda
    Boehnke, Michael
    Boerwinkle, Eric
    Bonnycastle, Lori L.
    Boomsma, Dorret I.
    Bornstein, Stefan R.
    Brown, Morris J.
    Burnier, Michel
    Cabrera, Claudia P.
    Chambers, John C.
    Chang, I-Shou
    Cheng, Ching-Yu
    Chines, Peter S.
    Chung, Ren-Hua
    Collins, Francis S.
    Connell, John M.
    Doring, Angela
    Dallongeville, Jean
    Danesh, John
    de Faire, Ulf
    Delgado, Graciela
    Dominiczak, Anna F.
    Doney, Alex S. F.
    Drenos, Fotios
    Edkins, Sarah
    Eicher, John D.
    Elosua, Roberto
    Enroth, Stefan
    Erdmann, Jeanette
    Eriksson, Per
    Esko, Tonu
    Evangelou, Evangelos
    Evans, Alun
    Fai, Tove
    Farra, Martin
    Felixl, Janine F.
    Ferrieres, Jean
    Ferrucci, Luigi
    Fornage, Myriam
    Forrester, Terrence
    Franceschinil, Nora
    Franco, Oscar H.
    Franco-Cereceda, Anders
    Fraser, Ross M.
    Ganesh, Santhi K.
    Gao, He
    Gertow, Karl
    Gianfagna, Francesco
    Gigante, Bruna
    Giulianini, Franco
    Goe, Anuj
    Goodall, Alison H.
    Goodarzi, Mark
    Gorski, Mathias
    Grassler, Jurgen
    Groves, Christopher J.
    Gudnason, Vilmundur
    Gyllensten, Ulf
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Biobank Research.
    Hartikainen, Anna-Liisa
    Hassinen, Maija
    Havulinna, Aki S.
    Hayward, Caroline
    Hercberg, Serge
    Herzig, Karl-Heinz
    Hicks, Andrew A.
    Hingorani, Aroon D.
    Hirschhorn, Joel N.
    Hofmanl, Albert
    Holmen, Jostein
    Holmen, Oddgeir Lingaas
    Hottenga, Jouke-Jan
    Howard, Phil
    Hsiung, Chao A.
    Hunt, Steven C.
    Ikram, M. Arfan
    Illig, Thomas
    Iribarren, Carlos
    Jensen, Richard A.
    Kahonen, Mika
    Kang, Hyun Min
    Kathiresan, Sekar
    Keating, Brendan J.
    Khaw, Kay-Tee
    Kim, Yun Kyoung
    Kim, Eric
    Kivimaki, Mika
    Klopp, Norman
    Kolovou, Genovefa
    Komulainen, Pirjo
    Kooner, Jaspal S.
    Kosova, Gulum
    Krauss, Ronald M.
    Kuh, Diana
    Kutalik, Zoltan
    Kuusisto, Johanna
    Kvaloy, Kirsti
    Lakka, Timo A.
    Lee, Nanette R.
    Lee, I-Te
    Lee, Wen-Jane
    Levy, Daniel
    Li, Xiaohui
    Liang, Kae-Woei
    Lin, Honghuang
    Lin, Li
    Lindstrom, Jaana
    Lobbens, Stephane
    Mannisto, Satu
    Muller, Gabriele
    Muller-Nurasyid, Martina
    Mach, Francois
    Markus, Hugh S.
    Marouli, Eirini
    McCarthy, Mark I.
    McKenzie, Colin A.
    Meneton, Pierre
    Menni, Cristina
    Metspalu, Andres
    Mijatovic, Vladan
    Moilanen, Leena
    Montasser, May E.
    Morris, Andrew D.
    Morrison, Alanna C.
    Mulas, Antonella
    Nagaraja, Ramaiah
    Narisu, Narisu
    Nikus, Kjell
    O'Donnell, Christopher J.
    O'Reilly, Paul F.
    Ong, Ken K.
    Paccaud, Fred
    Palmer, Cameron D.
    Parsa, Afshin
    Pedersen, Nancy L.
    Penninx, Brenda W.
    Perola, Markus
    Peters, Annette
    Poulter, Neil
    Pramstaller, Peter P.
    Psaty, Bruce M.
    Quertermous, Thomas
    Rao, Dabeeru C.
    Rasheed, Asif
    Rayner, N. William
    Renström, Frida
    Umeå University, Faculty of Medicine, Department of Biobank Research. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Malmö, Sweden.
    Rettig, Rainer
    Rice, Kenneth M.
    Roberts, Robert
    Rose, Lynda M.
    Rossouw, Jacques
    Samani, Nilesh J.
    Sanna, Serena
    Saramies, Jouko
    Schunkert, Heribert
    Sebert, Sylvain
    Sheu, Wayne H-H
    Shin, Young-Ah
    Sim, Xueling
    Smit, Johannes H.
    Smith, Albert V.
    Sosa, Maria X.
    Spector, Tim D.
    Stancakova, Alena
    Stanton, Alice V.
    Stirrups, Kathleen E.
    Stringham, Heather M.
    Sundstrom, Johan
    Swift, Amy J.
    Syvanen, Ann-Christine
    Tai, E-Shyong
    Tanaka, Toshiko
    Tarasov, Kirill V.
    Teumer, Alexander
    Thorsteinsdottir, Unnur
    Tobin, Martin D.
    Tremoli, Elena
    Uitterlinden, Andre G.
    Uusitupa, Matti
    Vaez, Ahmad
    Vaidya, Dhananjay
    van Duijn, Cornelia M.
    van Iperen, Erik P. A.
    Vasan, Ramachandran S.
    Verwoert, Germaine C.
    Virtamo, Jarmo
    Vitart, Veronique
    Voight, Benjamin F.
    Vollenweider, Peter
    Wagner, Aline
    Wain, Louise V.
    Wareham, Nicholas J.
    Watldns, Hugh
    Weder, Alan B.
    Westra, Harm Jan
    Wilks, Rainford
    Wilsgaard, Tom
    Wilson, James F.
    Wong, Tien Y.
    Yang, Tsun-Po
    Yao, Jie
    Yengo, Loic
    Zhang, Weihua
    Zhao, Jing Hua
    Zhu, Xiaofeng
    Bovet, Pascal
    Cooper, Richard S.
    Mohlke, Karen L.
    Saleheen, Danish
    Lee, Jong-Young
    Elliott, Paul
    Gierman, Hinco J.
    Willer, Cristen J.
    Franke, Lude
    Hovingh, G. Kees
    Taylor, Kent D.
    Dedoussis, George
    Sever, Peter
    Wong, Andrew
    Lind, Lars
    Assimes, Themistocles L.
    Njolstad, Inger
    Schwarz, Peter E. H.
    Langenberg, Claudia
    Snieder, Harold
    Caulfield, Mark J.
    Melander, E.
    Laakso, Markku
    Saltevo, Juha
    Rauramaa, Rainer
    Tuomilehto, Jaakko
    Ingelsson, Erik
    Lehtimaki, Terho
    Hveem, Kristian
    Palmas, Walter
    Marz, Winfried
    Kumar, Meena
    Salomaa, Veikko
    Chen, Yii-Der I.
    Rotter, Jerome I.
    Froguel, Philippe
    Jarvelin, Marjo-Riitta
    Lakatta, Edward G.
    Kuulasmaa, Kari
    Franks, Paul W.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Malmö, Sweden; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
    Hamsten, Anders
    Wichmann, H-Erich
    Palmer, Colin N. A.
    Stefansson, Kari
    Ridker, Paul M.
    Loos, Ruth J. F.
    Chalcravarti, Aravinda
    Deloukas, Panos
    Morris, Andrew P.
    Newton-Cheh, Christopher
    Munroe, Patricia B.
    The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals2016In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 48, no 10, p. 1171-1184Article in journal (Refereed)
    Abstract [en]

    To dissect the genetic architecture of blood pressure and assess effects on target organ damage, we analyzed 128,272 SNPs from targeted and genome-wide arrays in 201,529 individuals of European ancestry, and genotypes from an additional 140,886 individuals were used for validation. We identified 66 blood pressure-associated loci, of which 17 were new; 15 harbored multiple distinct association signals. The 66 index SNPs were enriched for cis-regulatory elements, particularly in vascular endothelial cells, consistent with a primary role in blood pressure control through modulation of vascular tone across multiple tissues. The 66 index SNPs combined in a risk score showed comparable effects in 64,421 individuals of non-European descent. The 66-SNP blood pressure risk score was significantly associated with target organ damage in multiple tissues but with minor effects in the kidney. Our findings expand current knowledge of blood pressure-related pathways and highlight tissues beyond the classical renal system in blood pressure regulation.

  • 37. Ekdahl, Kristina N.
    et al.
    Davoodpour, Padideh