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  • 101. Nilsson, Hanna
    et al.
    Holmberg, Henrik
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Nordin, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Groin hernia repair in women - A nationwide register study2018Ingår i: American Journal of Surgery, ISSN 0002-9610, E-ISSN 1879-1883, Vol. 216, nr 2, s. 274-279Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction: The aim of this study was to investigate reoperation for recurrence in men and women with respect to method of repair, hernia anatomy and year of operation. Method: Since 1992, groin hernia repairs performed in Sweden are prospectively registered in the Swedish Hernia Register, (SHR). Reoperations are noted, regardless of where the reoperation is performed. Risk of reoperation for recurrence is calculated for men and women with respect of method of repair, hernia anatomy and year of operation. Results: Out of 221 108 eligible operations registered between 1992-2013,17 545 (8%) were performed on women. The risk of being operated for recurrence after laparoscopic surgery was lowered in women, RR 0,4(95%CI 0.3-0.7) and increased in men, RR 2.3(95% CI 2.0-2.7), compared to the Lichtenstein technique. Discussion: The reoperation for recurrence rate differed significantly between men and women. As regards the technique used for primary repair, laparoscopic groin hernia repair lowered the risk of reoperation for recurrence in women whereas it doubled the risk in men.

  • 102.
    Nilsson, Ulf
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Kanerud, Isabel
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Diamant, Ulla-Britt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Blomberg, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Eriksson, Berne
    Lindberg, Anne
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    The prevalence of prolonged QTc increases by GOLD stage, and is associated with worse survival among subjects with COPD2019Ingår i: Heart & Lung, ISSN 0147-9563, E-ISSN 1527-3288, Vol. 48, nr 2, s. 148-154Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The role of QTc-prolongation, in relation to the increased mortality in COPD, is unclear.

    Objectives: To estimate the prevalence and prognostic impact, assessed as mortality, of QTc-prolongation in COPD, restrictive spirometric pattern (RSP), and normal lung function (NLF), respectively.

    Methods: All individuals (n = 993) with COPD and age- and sex-matched non-obstructive referents were identified from well-defined population-based cohorts examined in Northern Sweden in 2002–04. In 2005, the study-sample was invited to re-examination including ECG; QTc was calculated and mortality data collected until 31st December 2010.

    Results: The prevalence of QTc-prolongation was higher among people with RSP than among those with NLF and, although similar in NLF and COPD, the prevalence increased by COPD-severity. Among participants with COPD, those with QTc prolongation had higher mortality than those with normal QTc, while no such differences were found among participants with NLF or RSP.

    Conclusion: Among participants with COPD, the prevalence of QTc-prolongation increased by disease-severity and was associated with mortality.

  • 103. Njølstad, Pål Rasmus
    et al.
    Andreassen, Ole Andreas
    Brunak, Søren
    Borglum, Anders D.
    Dillner, Joakim
    Esko, Tonu
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin. Genetic and Molecular Epidemiology Unit, Lund University Diabetes Centre, Lund University, Malmö, Sweden; Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, MA, USA; Radclife Department of Medicine, University of Oxford, Oxford, UK.
    Freimer, Nelson
    Groop, Leif
    Heimer, Hakon
    Hougaard, David M.
    Hovig, Eivind
    Hveem, Kristian
    Jalanko, Anu
    Kaprio, Jaakko
    Knudsen, Gun Peggy
    Melbye, Mads
    Metspalu, Andres
    Mortensen, Preben Bo
    Palmgren, Juni
    Palotie, Aarno
    Reed, Wenche
    Stefansson, Hreinn
    Stitziel, Nathan O.
    Sullivan, Patrick F.
    Thorsteinsdottir, Unnur
    Vaudel, Marc
    Vuorio, Eero
    Werge, Thomas
    Stoltenberg, Camilla
    Stefansson, Kari
    Roadmap for a precision-medicine initiative in the Nordic region2019Ingår i: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 51, nr 6, s. 924-930Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    The Nordic region, comprising primarily Denmark, Estonia, Finland, Iceland, Norway and Sweden, has many of the necessary characteristics for being at the forefront of genome-based precision medicine. These include egalitarian and universal healthcare, expertly curated patient and population registries, biobanks, large population-based prospective cohorts linked to registries and biobanks, and a widely embraced sense of social responsibility that motivates public engagement in biomedical research. However, genome-based precision medicine can be achieved only through coordinated action involving all actors in the healthcare sector. Now is an opportune time to organize scientists in the Nordic region, together with other stakeholders including patient representatives, governments, pharmaceutical companies, academic institutions and funding agencies, to initiate a Nordic Precision Medicine Initiative. We present a roadmap for how this organization can be created. The Initiative should facilitate research, clinical trials and knowledge transfer to meet regional and global health challenges.

  • 104. Nordanstig, A.
    et al.
    Asplund, Kjell
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Norrving, B.
    Wahlgren, Nils
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin. Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Wester, P.
    Rosengren, L.
    Impact of the Swedish National Stroke Campaign on stroke awareness2017Ingår i: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 136, nr 4, s. 345-351Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Time delay from stroke onset to arrival in hospital is an important obstacle to widespread reperfusion therapy. To increase knowledge about stroke, and potentially decrease this delay, a 27-month national public information campaign was carried out in Sweden.

    Aims: To assess the effects of a national stroke campaign in Sweden.

    Methods: The variables used to measure campaign effects were knowledge of the AKUT test [a Swedish equivalent of the FAST (Face-Arm-Speech-Time)] test and intent to call 112 (emergency telephone number) . Telephone interviews were carried out with 1500 randomly selected people in Sweden at eight points in time: before, three times during, immediately after, and nine, 13 and 21 months after the campaign.

    Results: Before the campaign, 4% could recall the meaning of some or all keywords in the AKUT test, compared with 23% during and directly after the campaign, and 14% 21 months later. Corresponding figures were 15%, 51%, and 50% for those remembering the term AKUT and 65%, 76%, and 73% for intent to call 112 when observing or experiencing stroke symptoms. During the course of the campaign, improvement of stroke knowledge was similar among men and women, but the absolute level of knowledge for both items was higher for women at all time points.

    Conclusion: The nationwide campaign substantially increased knowledge about the AKUT test and intention to call 112 when experiencing or observing stroke symptoms, but knowledge declined post-intervention. Repeated public information therefore appears essential to sustain knowledge gains.

  • 105.
    Nordin, Pär
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Ahlberg, J.
    Johansson, H.
    Holmberg, Henrik
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Hafstrom, L.
    Risk factors for injuries associated with damage claims following groin hernia repair2017Ingår i: Hernia, ISSN 1265-4906, E-ISSN 1248-9204, Vol. 21, nr 2, s. 215-221Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Surgical repair of groin hernia should be carried out with minimal complication rates, and it is important to have regular quality control and accurate means of assessment. The Swedish healthcare system has a mutual insurance company (LA-F) that receives claims from patients who have suffered healthcare-related damage or malpractice. The Swedish Hernia Register (SHR) currently covers around 98% of all Swedish groin hernia operations. The aim of this study was to analyse damage claims following groin hernia repair surgery and link these with entries in the SHR, in order to identify risk factors and causes of injuries and malpractice associated with hernia repair. Data on all 48,574 groin hernia operations registered in the SHR between 2008 and 2010 were compared and linked with data on claims made to the Swedish National Patient Injury Insurance (LA-F). Of the 130 damage claims received by LA-F, 26 dealt with bleeding, 20 with testicular injury and 7 with intestinal lesions. Eighty (62%) of the complications were considered malpractice according to the Swedish Patient Injury Act. Acute and recurrent surgery, sutured repair and general anaesthesia were associated with a significantly increased risk for a damage claim independently the patients were compensated or not. Females filed claims in greater proportion than males. There was no significant difference in background factors between claims accepted by LA-F and compensated and those who were rejected compensation. Risk factors for filing a damage claim included acute surgery, operation for recurrence, sutured repair and general anaesthesia, whereas local anaesthesia reduced the risk.

  • 106.
    Näsman, Amanda
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Irewall, Tommie
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Hållmarker, Ulf
    Lindberg, Anne
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Stenfors, Nikolai
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Asthma and Asthma Medication Are Common among Recreational Athletes Participating in Endurance Sport Competitions2018Ingår i: Canadian Respiratory Journal, ISSN 1198-2241, Vol. 2018, artikel-id 3238546Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Asthma prevalence is high among elite endurance athletes, but little is known about its prevalence among competitive recreational athletes. The aim of this study was to determine the prevalence of self-reported asthma and asthma medication use among competitive recreational endurance athletes and their association with training.

    Methods: A web survey on asthma and medication was conducted among 38,603 adult participants of three Swedish endurance competitions (cross-country running, cross-country skiing, and swimming).

    Results: The overall response rate was 29%. The prevalence of self-reported asthma (physician-diagnosed asthma and use of asthma medication in the last 12 months) was 12%. Among those reporting asthma, 23% used inhaled corticosteroids and long-acting beta-agonists daily. We found no association between training volume and daily use of asthma medication, except a trend in relation to short-acting beta-agonists. Independent predictors of self-reported asthma were female sex, allergic rhinitis, previous eczema, family history of asthma, cycling, and training for >5 h 50 min/week.

    Conclusions: The prevalence of self-reported asthma among Swedish competitive recreational endurance athletes appears to be higher than that in the general Swedish population. A large proportion of recreational athletes were reported with asthma use medications, indicating an association between high physical activity and self-reported asthma among competitive recreational athletes.

  • 107.
    Ott, Michael
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Forssén, Björn
    Werneke, Ursula
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri. Sunderby Research Unit, Umeå University, Umeå, Sweden.
    Lithium treatment, nephrogenic diabetes insipidus and the risk of hypernatraemia: a retrospective cohort study2019Ingår i: Therapeutic Advances in Psychopharmacology, ISSN 2045-1253, E-ISSN 2045-1261, Vol. 9Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Hypernatraemia is a serious condition that can potentially become life threatening. It is known that lithium is associated with polyuria and nephrogenic diabetes insipidus, risk factors for hypernatraemia. In this study, we tested the hypothesis that lithium treatment was a risk factor for hypernatraemia.

    Methods: We performed a retrospective cohort study in the Swedish region of Norrbotten into the effects and potential adverse effects of lithium treatment and other mood stabilizers (LiSIE). For this particular study, we included all patients who had experienced at least one episode with a sodium concentration > 150 mmol/L between 1997 and 2013. Medical records were reviewed regarding past or current lithium exposure, diabetes insipidus and other potential risk factors for hypernatraemia.

    Results: Of 2463 patients included, 185 (7.5%) had experienced 204 episodes of hypernatraemia within the 17-year review period. In patients 65 years or older, infections dominated as the cause with 51%. In patients younger than 65 years, intoxications, particularly with alcohol, dominated as the cause with 35%. In the whole sample, dehydration accounted for 12% of episodes, 25% of which in the context of suspected or confirmed nephrogenic diabetes insipidus. Of all episodes, 25% resulted in death, with infection being the most common cause of death in 62% of cases.

    Conclusions: In our sample, infections and harmful use of substances including alcohol were the most common causes of hypernatraemia. Both current and past use of lithium also led to episodes of hypernatraemia, when associated with nephrogenic diabetes insipidus. Clinicians should remain vigilant, have a low threshold for checking sodium concentrations and consider even risk factors for hypernatraemia beyond lithium.

  • 108.
    Ott, Michael
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Mannchen, Julie K.
    Jamshidi, Fariba
    Werneke, Ursula
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri. Sunderby Research Unit.
    Management of severe arterial hypertension associated with serotonin syndrome: a case report analysis based on systematic review techniques2019Ingår i: Therapeutic Advances in Psychopharmacology, ISSN 2045-1253, E-ISSN 2045-1261, Vol. 9, s. 1-32Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Serotonin syndrome is thought to arise from serotonin excess. In many cases, symptoms are mild and self-limiting. But serotonin syndrome can become life threatening, when neuromuscular hyperexcitability spins out of control. Uncontainable neuromuscular hyperexcitability may lead to cardiovascular complications, linked to extreme changes in blood pressure. Currently, there is little guidance on how to control blood pressure in hyperserotonergic states. We report a case with treatment-resistant arterial hypertension, followed by a clinical review (using systematic review principles and techniques) of the available evidence from case reports published between 2004 and 2016 to identify measures to control arterial hypertension associated with serotonin syndrome. We conclude that classic antihypertensives may not be effective for the treatment of severe hypertension associated with serotonin syndrome. Benzodiazepines may lower blood pressure. Patients with severe hypertension not responding to benzodiazepines may benefit from cyproheptadine, propofol or both. In severe cases, higher cyproheptadine doses than currently recommended may be necessary.

  • 109.
    Otten, Julia
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Andersson, Jonas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Ståhl, Jens
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Stomby, Andreas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Saleh, Ahmed
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Waling, Maria
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för kostvetenskap.
    Ryberg, Mats
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Hauksson, Jon
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik. Department of Radiography and Biomedical Science, Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
    Svensson, Michael B.
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Avdelningen för idrottsmedicin.
    Johansson, Bengt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Olsson, Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Exercise Training Adds Cardiometabolic Benefits of a Paleolithic Diet in Type 2 Diabetes Mellitus2019Ingår i: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 8, nr 2, artikel-id e010634Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The accumulation of myocardial triglycerides and remodeling of the left ventricle are common features in type 2 diabetes mellitus and represent potential risk factors for the development of diastolic and systolic dysfunction. A few studies have investigated the separate effects of diet and exercise training on cardiac function, but none have investigated myocardial changes in response to a combined diet and exercise intervention. This 12-week randomized study assessed the effects of a Paleolithic diet, with and without additional supervised exercise training, on cardiac fat, structure, and function.

    Methods and Results: Twenty-two overweight and obese subjects with type 2 diabetes mellitus were randomized to either a Paleolithic diet and standard-care exercise recommendations ( PD ) or to a Paleolithic diet plus supervised exercise training 3 hours per week ( PD - EX ). This study includes secondary end points related to cardiac structure and function, ie, myocardial triglycerides levels, cardiac morphology, and strain were measured using cardiovascular magnetic resonance, including proton spectroscopy, at baseline and after 12 weeks. Both groups showed major favorable metabolic changes. The PD - EX group showed significant decreases in myocardial triglycerides levels (-45%, P=0.038) and left ventricle mass to end-diastolic volume ratio (-13%, P=0.008) while the left ventricle end-diastolic volume and stroke volume increased significantly (+14%, P=0.004 and +17%, P=0.008, respectively). These variables were unchanged in the PD group.

    Conclusions: Exercise training plus a Paleolithic diet reduced myocardial triglycerides levels and improved left ventricle remodeling in overweight/obese subjects with type 2 diabetes mellitus.

    Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 01513798.

  • 110.
    Otten, Julia
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Mellberg, Caroline
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Ryberg, Mats
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Sandberg, Susanne
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Kullberg, J
    Lindahl, Bernt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Larsson, C
    Hauksson, J
    Olsson, Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Strong and persistent effect on liver fat with a Paleolithic diet during a two-year intervention2016Ingår i: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 40, nr 5, s. 747-753Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND/OBJECTIVES: Our objective was to investigate changes in liver fat and insulin sensitivity during a 2-year diet intervention. An ad libitum Paleolithic diet (PD) was compared with a conventional low-fat diet (LFD).

    SUBJECTS/METHODS: Seventy healthy, obese, postmenopausal women were randomized to either a PD or a conventional LFD. Diet intakes were ad libitum. Liver fat was measured with proton magnetic resonance spectroscopy. Insulin sensitivity was evaluated with oral glucose tolerance tests and calculated as homeostasis model assessment-insulin resistance (HOMA-IR)/liver insulin resistance (Liver IR) index for hepatic insulin sensitivity and oral glucose insulin sensitivity (OGIS)/Matsuda for peripheral insulin sensitivity. All measurements were performed at 0, 6 and 24 months. Forty-one women completed the examinations for liver fat and were included.

    RESULTS: Liver fat decreased after 6 months by 64% (95% confidence interval: 54-74%) in the PD group and by 43% (27-59%) in the LFD group (P<0.01 for difference between groups). After 24 months, liver fat decreased 50% (25-75%) in the PD group and 49% (27-71%) in the LFD group. Weight reduction between baseline and 6 months was correlated to liver fat improvement in the LFD group (rs=0.66, P<0.01) but not in the PD group (rs=0.07, P=0.75). Hepatic insulin sensitivity improved during the first 6 months in the PD group (P<0.001 for Liver IR index and HOMA-IR), but deteriorated between 6 and 24 months without association with liver fat changes.

    CONCLUSIONS: A PD with ad libitum intake had a significant and persistent effect on liver fat and differed significantly from a conventional LFD at 6 months. This difference may be due to food quality, for example, a higher content of mono- and polyunsaturated fatty acids in the PD. Changes in liver fat did not associate with alterations in insulin sensitivity.International Journal of Obesity advance online publication, 16 February 2016; doi:10.1038/ijo.2016.4.

  • 111.
    Otten, Julia
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Ryberg, Mats
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Mellberg, Caroline
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Andersson, Tomas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Chorell, Elin
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Lindahl, Bernt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för hållbar hälsa.
    Larsson, Christel
    Department of Food and Nutrition, and Sport Science, Goteborgs Universitet, Goteborg, Sweden.
    Holst, Jens Juul
    Olsson, Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Postprandial levels of GLP-1, GIP, and glucagon after two years of weight loss with a Paleolithic diet: a randomized controlled trial in healthy obese women2019Ingår i: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 180, nr 6, s. 417-427Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: To investigate how weight loss by different diets impacts on postprandial levels of glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and glucagon.

    METHODS: In this single-centre, parallel group 2-year trial, 70 healthy postmenopausal obese women were randomized to the Paleolithic diet or a healthy control diet based on Nordic Nutrition Recommendations. Both diets were without calorie restriction. The primary outcome was the change in fat mass. Here, secondary analyses on GLP-1, GIP, and glucagon measured during an OGTT are described.

    RESULTS: In the Paleolithic diet group, mean weight loss compared to baseline was 11% at 6 months, and 10% at 24 months. In the control diet group, mean weight loss was 6% after 6 and 24 months (P = 0.0001 and P = 0.049 for the comparison between groups at 6 and 24 months respectively). Compared to baseline, the mean incremental area under the curve (iAUC) for GLP-1 increased by 34% and 45% after 6 and 24 months in the Paleolithic diet group, and increased by 59% after 24 months in the control diet group. The mean iAUC for GIP increased only in the Paleolithic diet group. The AUC for glucagon increased during the first 6 months in both groups. The fasting glucagon increase correlated with the β-hydroxybutyrate increase.

    CONCLUSIONS: Weight loss caused an increase in postprandial GLP-1 levels and a further rise occurred during weight maintenance. Postprandial GIP levels increased only after the Paleolithic diet. Reduced postprandial glucagon suppression may be caused by a catabolic state.

  • 112. Palmér, Robert
    et al.
    Mäenpää, Jukka
    Jauhiainen, Alexandra
    Larsson, Bengt
    Mo, John
    Russell, Muir
    Root, James
    Prothon, Susanne
    Chialda, Ligia
    Forte, Pablo
    Egelrud, Torbjörn
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Stenvall, Kristina
    Gardiner, Philip
    Dipeptidyl Peptidase 1 Inhibitor AZD7986 Induces a Sustained, Exposure-Dependent Reduction in Neutrophil Elastase Activity in Healthy Subjects2018Ingår i: Clinical Pharmacology and Therapeutics, ISSN 0009-9236, E-ISSN 1532-6535, Vol. 104, nr 6, s. 1155-1164Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Neutrophil serine proteases (NSPs), such as neutrophil elastase (NE), are activated by dipeptidyl peptidase 1 (DPP1) during neutrophil maturation. High NSP levels can be detrimental, particularly in lung tissue, and inhibition of NSPs is therefore an interesting therapeutic opportunity in multiple lung diseases, including chronic obstructive pulmonary disease (COPD) and bronchiectasis. We conducted a randomized, placebo-controlled, first-in-human study to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of single and multiple oral doses of the DPP1 inhibitor AZD7986 in healthy subjects. Pharmacokinetic and pharmacodynamic data were analyzed using nonlinear mixed effects modeling and showed that AZD7986 inhibits whole blood NE activity in an exposure-dependent, indirect manner-consistent with in vitro and preclinical predictions. Several dose-dependent, possibly DPP1-related, nonserious skin findings were observed, but these were not considered to prevent further clinical development. Overall, the study results provided confidence to progress AZD7986 to phase II and supported selection of a clinically relevant dose.

  • 113. Perotin, Jeanne-Marie
    et al.
    Schofield, James P. R.
    Wilson, Susan J.
    Ward, Jonathan
    Brandsma, Joost
    Strazzeri, Fabio
    Bansal, Aruna
    Yang, Xian
    Rowe, Anthony
    Corfield, Julie
    Lutter, Rene
    Shaw, Dominick E.
    Bakke, Per S.
    Caruso, Massimo
    Dahlén, Barbro
    Fowler, Stephen J.
    Horváth, Ildikó
    Howarth, Peter
    Krug, Norbert
    Montuschi, Paolo
    Sanak, Marek
    Sandström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Sun, Kai
    Pandis, Ioannis
    Auffray, Charles
    De Meulder, Bertrand
    Lefaudeux, Diane
    Riley, John H.
    Sousa, Ana R.
    Dahlen, Sven-Erik
    Adcock, Ian M.
    Chung, Kian Fan
    Sterk, Peter J.
    Skipp, Paul J.
    Collins, Jane E.
    Davies, Donna E.
    Djukanović, Ratko
    Epithelial dysregulation in obese severe asthmatics with gastro-oesophageal reflux2019Ingår i: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 53, nr 6, artikel-id 1900453Artikel i tidskrift (Refereegranskat)
  • 114.
    Peters, Björn
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin. Departments of Nephrology, Skaraborg Hospital, Skövde, Sweden.
    Hadimeri, Henrik
    Mölne, Johan
    Nasic, Salmir
    Jensen, Gert
    Stegmayr, Bernd
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Desmopressin (Octostim®) before a native kidney biopsy can reduce the risk for biopsy complications in patients with impaired renal function: a pilot study2018Ingår i: Nephrology (Carlton. Print), ISSN 1320-5358, E-ISSN 1440-1797, Vol. 23, nr 4, s. 366-370Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    AIM: To evaluate if the administration of desmopressin alters the risk for renal biopsy complications.

    METHODS: A multicenter registry containing 576 native kidney biopsies (NKb) with a serum creatinine above 150 µmol/L in 527 patients (372 men and 155 women, median age 61 years) was used. Most of the data were prospective. At one of the hospitals all biopsies with creatinine above 150 µmol/L received desmopressin before biopsies (NKb 204). These were compared to outcome of biopsy complications against other centres where desmopressin was not given (NKb 372). Fisher's exact test, χ2 analyses, univariate and multiple binary logistic regression were used. Data were given as Odds Ratio (OR) and Confidence Interval (CI). A two sided p-value of <0.05 was considered significant.

    RESULTS: In NKb with creatinine >150 µmol/L, those with desmopressin had less overall (3.4% versus 8.4%, OR 0.39, CI 0.17-0.90) whereas major or minor complications were not different. While desmopressin did not exhibit difference in complications in men, women received less major (0% versus 8.6%, p = 0.03) and overall complications (0% versus 12.1%, p = 0.006). A multiple logistic regression revealed that, after adjusting for BMI, age and sex, prophylaxis with desmopressin showed less major (OR 0.38, CI 0.15-0.96) and overall complications (OR 0.36, CI 0.15-0.85).

    CONCLUSION: Desmopressin given before a native kidney biopsy in patients with impaired renal function can reduce the risk for complications.

  • 115.
    Pilebro, Björn
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Arvidsson, Sandra
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Klinisk fysiologi.
    Lindqvist, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Klinisk fysiologi.
    Sundström, Torbjörn
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Westermark, Per
    Antoni, Gunnar
    Suhr, Ole
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Sörensen, Jens
    Positron emission tomography (PET) utilizing Pittsburgh compound B (PIB) for detection of amyloid heart deposits in hereditary transthyretin amyloidosis (ATTR)2018Ingår i: Journal of Nuclear Cardiology, ISSN 1071-3581, E-ISSN 1532-6551, Vol. 25, nr 1, s. 240-248Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: DPD scintigraphy has been advocated for imaging cardiac amyloid in ATTR amyloidosis. PET utilizing 11C-Pittsburgh compound B (PIB) is the gold standard for imaging brain amyloid in Alzheimer’s disease. PIB was recently shown to identify cardiac amyloidosis in both AL and ATTR amyloidosis. In the ATTR population, two types of amyloid fibrils exist, one containing fragmented and full-length TTR (type A) and the other only full-length TTR (type B). The aim of this study was to further evaluate PIB-PET in patients with hereditary ATTR amyloidosis.

    Methods: Ten patients with biopsy-proven V30M ATTR amyloidosis and discrete or no signs of cardiac involvement were included. Patients were grouped according to TTR-fragmentation. All underwent DPD scintigraphy, echocardiography, and PIB-PET. A left ventricular PIB-retention index (PIB-RI) was established and compared to five normal volunteers.

    Results: PIB-RI was increased in all patients (P < 0.001), but was significantly higher in type B than in type A (0.129 ± 0.041 vs 0.040 ± 0.006 min−1, P = 0.009). Cardiac DPD uptake was elevated in group A and absent in group B.

    Conclusion: PIB-PET, in contrast to DPD scintigraphy, has the potential to specifically identify cardiac amyloid depositions irrespective of amyloid fibril composition. The heart appears to be a target organ for amyloid deposition in ATTR amyloidosis.

  • 116. Poniku, Afrim
    et al.
    Bajraktari, Gani
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi. Clinic of Cardiology, University Clinical Centre of Kosova, Prishtina, Kosovo; Medical Faculty, University of Prishtina, Prishtina, Kosovo.
    Elezi, Shpend
    Ibrahimi, Pranvera
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin. Clinic of Cardiology, University Clinical Centre of Kosova, Prishtina, Kosovo.
    Henein, Michael Y.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Adiponectin correlates with body mass index and to a lesser extent with left ventricular mass in dialysis patients2018Ingår i: Cardiology Journal, ISSN 1897-5593, Vol. 25, nr 4, s. 501-511Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Adiponectin is a serum protein produced by adipose tissue which exerts anti-inflammatory, anti-diabetic and anti-atherosclerotic properties, hence is considered a cardio-protective marker. With the current uncertain role of adiponectin in dialysis patients to the aim of this study was to investigate its relationship with left ventricular (LV) structure and function in these patients.

    Methods: This study included 89 (age 56 +/- 13 years, 43% male) patients treated with regular dialysis for > 6 months, and 55 control subjects with normal renal function. A complete two-dimensional, M- ode and tissue-Doppler echocardiographic study, and biochemical blood analyses, adiponectin and anthropometric parameters were obtainedon the same day.

    Results: Dialysis patients had lower body mass index (BMI) and lower body surface area (BSA) (p < 0.001 for both), lower waist/hips ratio (p = 0.005), higher LV mass index (LVMI, p < 0.001), higher adiponectin level (p < 0.001) and LV end-systolic volume p = 0.003), lower LV ejection fraction (p = 0.006), longer isovolumic relaxation time (p < 0.001), lower mean LV strain (p = 0.002), larger left atrium volume (p = 0.022) and lower left atrium emptying fraction (p = 0.026), compared to controls. In dialysis patients, adiponectin correlated with waist circumference (r = -0.427, p < 0.001), BMI (r = -0.403, p < 0.001) and BSA (r = -0.480, p < 0.001), and to a lesser extent with LVMI (r = 0.296, p = 0.005), waist/hips ratio (r = -0.222, p = 0.037) and total cholesterol (r = -0.292, p = 0.013). But in controls, it correlated only modestly with age (r = 0.304, p = 0.024), hemoglobin (r = 0.371, p = 0.005), high density lipoprotein cholesterol (r = 0.315, p = 0.019) and LVMI (r = 0277, p = 0.043).

    Conclusions: It seems that in dialysis patients, adiponectin modest correlation with anthropometric measurements suggests an ongoing catabolic process rather than a change in ventricular function.

  • 117.
    Preet, Raman
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Khan, Nausheen
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Blomstedt, Yulia
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Nilsson, Maria
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Stewart Williams, Jennifer
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa. Priority Research Centre for Generational Health and Ageing, Faculty of Health and Medicine, University of Newcastle, Newcastle, NSW, Australia.
    Assessing dental professionals' understanding of tobacco prevention and control: a qualitative study in Västerbotten County, Sweden2016Ingår i: BDJ Open, ISSN 2056-807X, nr 2, s. 1-6, artikel-id 16009Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aim: To assess dental professionals’ understanding of tobacco prevention and control.

    Materials and methods: In Sweden dental hygienists receive training in tobacco prevention and control. The study setting is Västerbotton County in the north of Sweden where a number of successful tobacco control initiatives have been established. A purposeful sample comprising five male and four female dental professionals and trainees was selected. Data were collected through in-depth semi-structured individual interviews and analysed using content analysis.

    Results: Informants acknowledged limited adherence to tobacco prevention. They were not confident of their knowledge of tobacco and non-communicable disease prevention and had limited awareness of global oral health policies. Reasons for poor adherence included professional fragmentation, lack of training, and the absence of reimbursement for time spent on prevention activities.

    Discussion: The success of efforts to reduce smoking in Västerbotton County is attributed to the network of local public health initiatives with very limited involvement by local dental professionals.

    Conclusions: The findings highlight the need to more actively engage the dental workforce in tobacco control and prevention. Moreover, it is important to recognise that dental professionals can be public health advocates for tobacco control and prevention at global, national and local levels.

  • 118. Ragnarsson, Oskar
    et al.
    Olsson, Daniel S.
    Chantzichristos, Dimitrios
    Papakokkinou, Eleni
    Dahlqvist, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Segerstedt, Elin
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Olsson, Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Petersson, Maria
    Berinder, Katarina
    Bensing, Sophie
    Hoybye, Charlotte
    Eden Engström, Britt
    Burman, Pia
    Bonelli, Lorenza
    Follin, Cecilia
    Petranek, David
    Erfurth, Eva Marie
    Wahlberg, Jeanette
    Ekman, Bertil
    Åkerman, Anna-Karin
    Schwarcz, Erik
    Bryngelsson, Ing-Liss
    Johannsson, Gudmundur
    The incidence of Cushing's disease: a nationwide Swedish study2019Ingår i: Pituitary, ISSN 1386-341X, E-ISSN 1573-7403, Vol. 22, nr 2, s. 179-186Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Studies on the incidence of Cushing’s disease (CD) are few and usually limited by a small number of patients. The aim of this study was to assess the annual incidence in a nationwide cohort of patients with presumed CD in Sweden.

    Methods: Patients registered with a diagnostic code for Cushing’s syndrome (CS) or CD, between 1987 and 2013 were identified in the Swedish National Patient Registry. The CD diagnosis was validated by reviewing clinical, biochemical, imaging, and histopathological data.

    Results: Of 1317 patients identified, 534 (41%) had confirmed CD. One-hundred-and-fifty-six (12%) patients had other forms of CS, 41 (3%) had probable but unconfirmed CD, and 334 (25%) had diagnoses unrelated to CS. The mean (95% confidence interval) annual incidence between 1987 and 2013 of confirmed CD was 1.6 (1.4–1.8) cases per million. 1987–1995, 1996–2004, and 2005–2013, the mean annual incidence was 1.5 (1.1–1.8), 1.4 (1.0–1.7) and 2.0 (1.7–2.3) cases per million, respectively. During the last time period the incidence was higher than during the first and second time periods (P < 0.05).

    Conclusion: The incidence of CD in Sweden (1.6 cases per million) is in agreement with most previous reports. A higher incidence between 2005 and 2013 compared to 1987–2004 was noticed. Whether this reflects a truly increased incidence of the disease, or simply an increased awareness, earlier recognition, and earlier diagnosis can, however, not be answered. This study also illustrates the importance of validation of the diagnosis of CD in epidemiological research.

  • 119. Ricci, Cristian
    et al.
    Wood, Angela
    Muller, David
    Gunter, Marc J.
    Agudo, Antonio
    Boeing, Heiner
    van der Schouw, Yvonne T.
    Warnakula, Samantha
    Saieva, Calogero
    Spijkerman, Annemieke
    Sluijs, Ivonne
    Tjonneland, Anne
    Kyro, Cecilie
    Weiderpass, Elisabete
    Kuehn, Tilman
    Kaaks, Rudolf
    Sanchez, Maria-Jose
    Panico, Salvatore
    Agnoli, Claudia
    Palli, Domenico
    Tumino, Rosario
    Engstrom, Gunnar
    Melander, Olle
    Bonnet, Fabrice
    Boer, Jolanda M. A.
    Key, Timothy J.
    Travis, Ruth C.
    Overvad, Kim
    Verschuren, W. M. Monique
    Quiros, J. Ramon
    Trichopoulou, Antonia
    Papatesta, Eleni-Maria
    Peppa, Eleni
    Iribas, Conchi Moreno
    Gavrila, Diana
    Forslund, Ann-Sofie
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Jansson, Jan-Håkan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Matullo, Giuseppe
    Arriola, Larraitz
    Freisling, Heinz
    Lassale, Camille
    Tzoulaki, Ioanna
    Sharp, Stephen J.
    Forouhi, Nita G.
    Langenberg, Claudia
    Saracci, Rodolfo
    Sweeting, Michael
    Brennan, Paul
    Butterworth, Adam S.
    Riboli, Elio
    Wareham, Nick J.
    Danesh, John
    Ferrari, Pietro
    Alcohol intake in relation to non-fatal and fatal coronary heart disease and stroke: EPIC-CVD case-cohort study2018Ingår i: BMJ. British Medical Journal, E-ISSN 1756-1833, Vol. 361, artikel-id k934Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE To investigate the association between alcohol consumption (at baseline and over lifetime) and non-fatal and fatal coronary heart disease (CHD) and stroke. DESIGN Multicentre case-cohort study. SETTING A study of cardiovascular disease (CVD) determinants within the European Prospective Investigation into Cancer and nutrition cohort (EPIC-CVD) from eight European countries. PARTICIPANTS 32 549 participants without baseline CVD, comprised of incident CVD cases and a subcohort for comparison. MAIN OUTCOME MEASURES Non-fatal and fatal CHD and stroke (including ischaemic and haemorrhagic stroke). RESULTS There were 9307 non-fatal CHD events, 1699 fatal CHD, 5855 non-fatal stroke, and 733 fatal stroke. Baseline alcohol intake was inversely associated with non-fatal CHD, with a hazard ratio of 0.94 (95% confidence interval 0.92 to 0.96) per 12 g/day higher intake. There was a J shaped association between baseline alcohol intake and risk of fatal CHD. The hazard ratios were 0.83 (0.70 to 0.98), 0.65 (0.53 to 0.81), and 0.82 (0.65 to 1.03) for categories 5.0-14.9 g/day, 15.0-29.9 g/day, and 30.0-59.9 g/day of total alcohol intake, respectively, compared with 0.1-4.9 g/ day. In contrast, hazard ratios for non-fatal and fatal stroke risk were 1.04 (1.02 to 1.07), and 1.05 (0.98 to 1.13) per 12 g/day increase in baseline alcohol intake, respectively, including broadly similar findings for ischaemic and haemorrhagic stroke. Associations with cardiovascular outcomes were broadly similar with average lifetime alcohol consumption as for baseline alcohol intake, and across the eight countries studied. There was no strong evidence for interactions of alcohol consumption with smoking status on the risk of CVD events. CONCLUSIONS Alcohol intake was inversely associated with non-fatal CHD risk but positively associated with the risk of different stroke subtypes. This highlights the opposing associations of alcohol intake with different CVD types and strengthens the evidence for policies to reduce alcohol consumption.

  • 120.
    Röding, Fredrik
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi.
    Lindkvist, Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa. Umeå universitet, Samhällsvetenskapliga fakulteten, Handelshögskolan vid Umeå universitet, Statistik.
    Bergström, Ulrica
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi.
    Svensson, Olle
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi.
    Lysholm, Jack
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Trauma recidivism at an emergency department of a Swedish medical center2016Ingår i: Injury Epidemiology, ISSN 0176-3733, E-ISSN 2197-1714, Vol. 3, artikel-id 22Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: To inform targeted prevention, we studied patterns of trauma recidivism and whether a first injury predicts the risk for a recurrent injury.

    METHODS: In a population-based study of 98,502 adult injury events 1999-2012, at the emergency department of Umeå University Hospital, Sweden, we compared non-recidivists with recidivists in terms of patients' sex, age, type of injury and severity of the injury.

    RESULTS: Thirty-six percent of all patients suffered recurrent injuries, which were associated with a higher proportion of inpatient care and more hospital days. Young men and elderly women were at the highest risk for trauma recidivism. At 20 to 24 years, men had a 2.4 (CI 95 % 2.3-2.5) higher risk than women, a 90 years old woman had almost a 10-fold higher risk for another moderate/severe injury than a 20 years old one. A fracture were associated with a hazard ratio of 1.28 (CI 95 % 1.15-1.42) among men younger than 65 years and 1.31 (CI 95 % 1.12-1.54) for men older than 65 years for a subsequent moderate/severe injury. For women younger than 65 years a fracture was associated with a hazard ratio of 1.44 (CI 95 % 1.28-1.62) for a subsequent moderate/severe injury. A sprain carries a higher risk for a new moderate/severe injury for both men and women and in both age groups; the hazard ratio was 1.13 (CI 95 % 1.00-1.26) for men younger than 65 years, 1.42 (CI 95 % 1.01-1.99) for men older than 65 years, 1.19 (CI 95 % 1.05-1.35) for women younger than 65 years and 1.26 (CI 95 % 1.02-1.56) for women older than 65 years. A higher degree of injury severity was associated with a higher risk for a new moderate/severe injury.

    CONCLUSION: Trauma recidivism is common and represents a large proportion of all injured. Age and sex are associated with the risk for new injury. Injury types and severity, also have implications for future injury.

  • 121.
    Sawalha, Sami
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Hedman, Linnea
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för hållbar hälsa.
    Backman, Helena
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för hållbar hälsa.
    Stenfors, Nikolai
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Rönmark, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för hållbar hälsa.
    Lundback, Bo
    Lindberg, Anne
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    The impact of comorbidities on mortality among men and women with COPD: report from the OLIN COPD study2019Ingår i: THERAPEUTIC ADVANCES IN RESPIRATORY DISEASE, ISSN 1753-4658, Vol. 13, artikel-id 1753466619860058Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Comorbidities probably contribute to the increased mortality observed among subjects with chronic obstructive pulmonary disease (COPD), but sex differences in the prognostic impact of comorbidities have rarely been evaluated in population-based studies. The aim of this study was to evaluate the impact of common comorbidities, cardiovascular disease (CVD), diabetes mellitus (DM), and anxiety/depression (A/D), on mortality among men and women with and without airway obstruction in a population-based study. Methods: All subjects with airway obstruction [forced expiratory volume in 1 second (FEV1)/(forced) vital capacity ((F)VC) <0.70, n = 993] were, together with age- and sex-matched referents, identified after examinations of population-based cohorts in 2002-2004. Spirometric groups: normal lung function (NLF) and COPD (post-bronchodilator FEV1/(F)VC <0.70) and additionally, LLN-COPD (FEV1/(F)VC <lower limit of normal). Mortality data was collected until December 2015. Results: In COPD, the prevalence of CVD and DM was higher in men, whereas the prevalence of A/D was higher in women. The cumulative mortality was significantly higher in COPD than NLF, and higher in men than women in both groups. Among women with COPD, CVD and A/D but not DM increased the risk of death independent of age, body mass index, smoking habits, and disease severity, whereas among men DM and A/D but not CVD increased the risk for death. When the LLN criterion was applied, the pattern was similar. Conclusion: There were sex-dependent differences regarding the impact of comorbidities on prognosis in COPD. Even though the prevalence of CVD was higher in men, the impact of CVD on mortality was higher in women, and despite higher prevalence of A/D in women, the impact on mortality was similar in both sexes. The reviews of this paper are available via the supplemental material section.

  • 122. Schofield, James P. R.
    et al.
    Burg, Dominic
    Nicholas, Ben
    Strazzeri, Fabio
    Brandsma, Joost
    Staykova, Doroteya
    Folisi, Caterina
    Bansal, Aruna T.
    Xian, Yang
    Guo, Yike
    Rowe, Anthony
    Corfield, Julie
    Wilson, Susan
    Ward, Jonathan
    Lutter, Rene
    Shaw, Dominick E.
    Bakke, Per S.
    Caruso, Massimo
    Dahlen, Sven-Erik
    Fowler, Stephen J.
    Horvath, Ildiko
    Howarth, Peter
    Krug, Norbert
    Montuschi, Paolo
    Sanak, Marek
    Sandström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Sun, Kai
    Pandis, Ioannis
    Riley, John
    Auffray, Charles
    De Meulder, Bertrand
    Lefaudeux, Diane
    Sousa, Ana R.
    Adcock, Ian M.
    Chung, Kian Fan
    Sterk, Peter J.
    Skipp, Paul J.
    Djukanovic, Ratko
    Ahmed, H.
    Allen, D.
    Badorrek, P.
    Ballereau, S.
    Baribaud, F.
    Batuwitage, M. K.
    Bedding, A.
    Behndig, A. F.
    Berglind, A.
    Berton, A.
    Bigler, J.
    Boedigheimer, M. J.
    Bonnelykke, K.
    Brinkman, P.
    Bush, A.
    Campagna, D.
    Casaulta, C.
    Chaiboonchoe, A.
    Davison, T.
    De Meulder, B.
    Delin, I.
    Dennison, P.
    Dodson, P.
    El Hadjam, L.
    Erzen, D.
    Faulenbach, C.
    Fichtner, K.
    Fitch, N.
    Formaggio, E.
    Gahlemann, M.
    Galffy, G.
    Garissi, D.
    Garret, T.
    Gent, J.
    Guillmant-Farry, E.
    Henriksson, E.
    Hoda, U.
    Hohlfeld, J. M.
    Hu, X.
    James, A.
    Johnson, K.
    Jullian, N.
    Kerry, G.
    Klueglich, M.
    Knowles, R.
    Konradsen, J. R.
    Kretsos, K.
    Krueger, L.
    Lantz, A. -S
    Larminie, C.
    Latzin, P.
    Lefaudeux, D.
    Lemonnier, N.
    Lowe, L. A.
    Lutter, R.
    Manta, A.
    Mazein, A.
    McEvoy, L.
    Menzies-Gow, A.
    Mores, N.
    Murray, C. S.
    Nething, K.
    Nihlen, U.
    Niven, R.
    Nordlund, B.
    Nsubuga, S.
    Pellet, J.
    Pison, C.
    Pratico, G.
    Puig Valls, M.
    Riemann, K.
    Rocha, J. P.
    Rossios, C.
    Santini, G.
    Saqi, M.
    Scott, S.
    Sehgal, N.
    Selby, A.
    Soderman, P.
    Sogbesan, A.
    Spycher, F.
    Stephan, S.
    Stokholm, J.
    Sunther, M.
    Szentkereszty, M.
    Tamasi, L.
    Tariq, K.
    Valente, S.
    van Aalderen, W. M.
    van Drunen, C. M.
    Van Eyll, J.
    Vyas, A.
    Yu, W.
    Zetterquist, W.
    Zolkipli, Z.
    Zwinderman, A. H.
    Adriaens, Nora
    Aliprantis, Antonios
    Alving, Kjell
    Bakke, Per
    Balgoma, David
    Barber, Clair
    Baribaud, Frederic
    Bates, Stewart
    Bautmans, An
    Beleta, Jorge
    Bochenek, Grazyna
    Braun, Armin
    Carayannopoulos, Leon
    Rocha, Joao Pedro Carvalho da Purificacao
    Chaleckis, Romanas
    D'Amico, Arnaldo
    De Alba, Jorge
    De Lepeleire, Inge
    Dekker, Tamara
    Dijkhuis, Annemiek
    Draper, Aleksandra
    Edwards, Jessica
    Emma, Rosalia
    Ericsson, Magnus
    Flood, Breda
    Gallart, Hector
    Gomez, Cristina
    Gove, Kerry
    Gozzard, Neil
    Haughney, John
    Hewitt, Lorraine
    Hohlfeld, Jens
    Holweg, Cecile
    Hu, Richard
    Hu, Sile
    Kamphuis, Juliette
    Kennington, Erika J.
    Kerry, Dyson
    Knobel, Hugo
    Kolmert, Johan
    Kots, Maxim
    Kuo, Scott
    Kupczyk, Maciej
    Lambrecht, Bart
    Lone-Latif, Saeeda
    Loza, Matthew J.
    Marouzet, Lisa
    Martin, Jane
    Masefield, Sarah
    Mathon, Caroline
    Meah, Sally
    Meiser, Andrea
    Metcalf, Leanne
    Mikus, Maria
    Miralpeix, Montse
    Monk, Philip
    Naz, Shama
    Nilsson, Peter
    Ostling, Jorgen
    Pacino, Antonio
    Palkonen, Susanna
    Pavlidis, Stelios
    Pennazza, Giorgio
    Petren, Anne
    Pink, Sandy
    Postle, Anthony
    Powell, Pippa
    Rahman-Amin, Malayka
    Rao, Navin
    Ravanetti, Lara
    Ray, Emma
    Reinke, Stacey
    Reynolds, Leanne
    Robberechts, Martine
    Roberts, Amanda
    Russell, Kirsty
    Rutgers, Michael
    Santoninco, Marco
    Schoelch, Corinna
    Sjodin, Marcus
    Smids, Barbara
    Smith, Caroline
    Smith, Jessica
    Smith, Katherine M.
    Thorngren, John-Olof
    Thornton, Bob
    Thorsen, Jonathan
    van de Pol, Marianne
    van Geest, Marleen
    Versnel, Jenny
    Vink, Anton
    Wald, Frans
    Walker, Samantha
    Weiszhart, Zsoka
    Wetzel, Kristiane
    Wheelock, Craig E.
    Wiegman, Coen
    Williams, Sian
    Wilson, Susan J.
    Woodcock, Ashley
    Yang, Xian
    Yeyasingham, Elizabeth
    Prins, Jan-Bas
    Gahlemann, Martina
    Visintin, Luigi
    Evans, Hazel
    Puhl, Martine
    Buzermaniene, Lina
    Hudson, Val
    Bond, Laura
    de Boer, Pim
    Widdershoven, Guy
    Sigmund, Ralf
    Supple, David
    Hamerlijnck, Dominique
    Negus, Jenny
    Kamphuis, Julitte
    Sergison, Lehanne
    Onstein, Susanne
    MacNee, William
    Bernardini, Renato
    Bont, Louis
    Wecksell, Per-Ake
    Stratification of asthma phenotypes by airway proteomic signatures2019Ingår i: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 144, nr 1, s. 70-82Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Stratification by eosinophil and neutrophil counts increases our understanding of asthma and helps target therapy, but there is room for improvement in our accuracy in prediction of treatment responses and a need for better understanding of the underlying mechanisms.

    Objective: We sought to identify molecular subphenotypes of asthma defined by proteomic signatures for improved stratification.

    Methods: Unbiased label-free quantitative mass spectrometry and topological data analysis were used to analyze the proteomes of sputum supernatants from 246 participants (206 asthmatic patients) as a novel means of asthma stratification. Microarray analysis of sputum cells provided transcriptomics data additionally to inform on underlying mechanisms.

    Results: Analysis of the sputum proteome resulted in 10 clusters (ie, proteotypes) based on similarity in proteomic features, representing discrete molecular subphenotypes of asthma. Overlaying granulocyte counts onto the 10 clusters as metadata further defined 3 of these as highly eosinophilic, 3 as highly neutrophilic, and 2 as highly atopic with relatively low granulocytic inflammation. For each of these 3 phenotypes, logistic regression analysisidentified candidate protein biomarkers, and matched transcriptomic data pointed to differentially activated underlying mechanisms.

    Conclusion: This study provides further stratification of asthma currently classified based on quantification of granulocytic inflammation and provided additional insight into their underlying mechanisms, which could become targets for novel therapies.

  • 123.
    Sjögren, Vilhelm
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Byström, Björn
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Renlund, Henrik
    Svensson, Peter J.
    Oldgren, Jonas
    Norrving, Bo
    Själander, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Non-vitamin K oral anticoagulants are non-inferior for stroke prevention but cause fewer major bleedings than well-managed warfarin: a retrospective register study2017Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, nr 7, artikel-id e0181000Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background For patients with atrial fibrillation, non-vitamin K oral anticoagulants, or NOACs (dabigatran, rivaroxaban, edoxaban, and apixaban) have been proven non-inferior or superior to warfarin in preventing stroke and systemic embolism, and in risk of haemorrhage. In the pivotal NOAC studies, quality of warfarin treatment was poor with mean time in therapeutic range (TTR) 55-65%, compared with >= 70% in Swedish clinical practice. Methods We compared NOACs (as a group) to warfarin in non-valvular atrial fibrillation, studying all 12,694 patients starting NOAC treatment within the Swedish clinical register and dosing system Auricula, from July 1, 2011 to December 31, 2014, and matching them to 36,317 patients starting warfarin using propensity scoring. Endpoints were thromboembolic events and major bleedings that were fatal or required hospital care. Outcome data were collected from validated Swedish hospital administrative and clinical registers. Results Mean age was 72.2 vs 72.3 years, proportion of males 58.2% vs 57.0%, and mean follow-up time 299 vs 283 days for NOACs and warfarin. Distribution of NOACs was: dabigatran 40.3%, rivaroxaban 31.2%, and apixaban 28.5%. Mean TTR was 70%. There were no significant differences in rates of thromboembolic/thrombotic events or gastrointestinal bleeding. NOAC treated patients had lower rates of major bleeding overall, hazard ratio 0.78 (95% confidence interval 0.67-0.92), intracranial bleeding 0.59 (0.40-0.87), haemorrhagic stroke 0.49 (0.28-0.86), and other major bleeding 0.71 (0.57-0.89). Conclusion For patients with atrial fibrillation, NOACs are as effective for stroke prevention as well-managed warfarin but cause fewer major bleedings.

  • 124.
    Sjögren, Vilhelm
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Grzymala-Lubanski, Bartosz
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Renlund, Henrik
    Svensson, Peter
    Själander, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Safety and Efficacy of Bridging With Low-Molecular-Weight Heparin During Temporary Interruptions of Warfarin: A Register-Based Cohort Study2017Ingår i: Clinical and applied thrombosis/hemostasis, ISSN 1076-0296, E-ISSN 1938-2723, Vol. 23, nr 8, s. 961-966Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Low-molecular-weight heparin (LMWH) is often recommended as a bridging therapy during temporary interruptions in warfarin treatment, despite lack of evidence. The aim of this study was to see whether we could find benefit from LMWH bridging. We studied all planned interruptions of warfarin within the Swedish anticoagulation register Auricula during 2006 to 2011. Low-molecular-weight heparin bridging was compared to nonbridging (control) after propensity score matching. Complications were identified in national clinical registers for 30 days following warfarin cessation, and defined as all-cause mortality, bleeding (intracranial, gastrointestinal, or other), or thrombosis (ischemic stroke or systemic embolism, venous thromboembolism, or myocardial infarction) that was fatal or required hospital care. Of the 14 556 identified warfarin interruptions, 12 659 with a known medical background had a mean age of 69 years, 61% were males, mean CHADS2 (1 point for each of congestive heart failure, hypertension, age >/=75 years, diabetes, and 2 points for stroke or transient ischemic attack) score was 1.7, and CHA2DS2-VASc score was 3.4. The total number of LMWH bridgings was 7021. Major indications for anticoagulation were mechanical heart valve prostheses 4331, atrial fibrillation 1097, and venous thromboembolism 1331. Bridging patients had a higher rate of thrombotic events overall. Total risk of any complication did not differ significantly between bridging (1.5%) and nonbridging (1.2%). Regardless of indication for warfarin treatment, we found no benefit from bridging. The type of procedure prompting bridging was not known, and the likely reason for the observed higher risk of thrombosis with LMWH bridging is that low-risk procedures more often meant no bridging. Results from randomized trials are needed, especially for patients with mechanical heart valves.

  • 125.
    Skagerlind, Malin
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för omvårdnad. Department of Nephrology, Centre of Medicine, University Hospital of Umeå, Umeå, Sweden.
    Stegmayr, Bernd
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    An evaluation of four modes of low-dose anticoagulation during intermittent haemodialysis2018Ingår i: European Journal of Clinical Pharmacology, ISSN 0031-6970, E-ISSN 1432-1041, Vol. 74, nr 3, s. 267-274Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Intensive care participants that need dialysis frequently suffer from increased risk of bleeding. Standard intermittent haemodialysis (SHD) includes anticoagulation to avoid clotting of the dialysis system. The aim of this study was to clarify which of four different low-dose anticoagulant modes was preferable in reducing the exposure to i.v. unfractionated heparin (heparin) and maintaining patency of the dialysis circuit. Twenty-three patients on SHD were included to perform haemodialysis with four modes of low-dose anticoagulation. For comparative analyses, patients served as their own control. Haemodialysis with a single bolus of tinzaparin at the start was compared to haemodialysis initiated without i.v. heparin but priming with (1) heparin in saline (H), (2) heparin and albumin in saline (HA), (3) heparin and albumin in combination with a citrate-containing dialysate (HAC), (4) saline and usinga heparin-coated filters (EvodialA (R)). The priming fluid was discarded before dialysis started. Blood samples were collected at 0, 30 and 180 min during haemodialysis. Smaller bolus doses of heparin (500 Units/dose) were allowed during the modes to avoid interruption by clotting. The mean activated partial thromboplastin (APTT) time as well as the doses of anticoagulation administered was highest with SHD and least with HAC and EvodialA (R). Mode H versus SHD had the highest rate of prematurely interrupted dialyses (33%, p = 0.008). The urea reduction rate was less with EvodialA (R) vs. SHD (p < 0.01). One hypersensitivity reaction occurred with EvodialA (R). Changes in blood cell concentrations and triglycerides differed between the modes. If intermittent haemodialysis is necessary in patients at risk of bleeding, anticoagulation using HAC and EvodialA (R) appeared most preferable with least administration of heparin, lowest APTT increase and lowest risk for prematurely clotted dialyzers in contrast to the least plausible H mode.

  • 126.
    Suhr, Ole B
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Wixner, Jonas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Pilebro, Björn
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Lundgren, Hans-Erik
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Anan, Intissar
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    The Swedish landscape of hereditary ATTR amyloidosis2017Ingår i: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 24, nr 1, s. 93-94Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Northern Sweden is a well-known clustering area for hereditary transthyretin (TTR) amyloid (ATTR) amyloidosis caused by the Val30Met mutation. However, several additional mutations have been found in the Swedish population, of which many, such as the Ala45Ser, Gly57Arg and His88Arg mutations, have not been reported outside of Sweden to the best of our knowledge. We aim to give an overview of the various mutations found in the Swedish population.

  • 127. Sundh, Josefin
    et al.
    Bornefalk-Hermansson, Anna
    Ahmadi, Zainab
    Blomberg, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Janson, Christer
    Currow, David C.
    McDonald, Christine F.
    McCaffrey, Nikki
    Ekström, Magnus
    REgistry-based randomized controlled trial of treatment and Duration and mortality in long-term OXygen therapy (REDOX) study protocol2019Ingår i: BMC Pulmonary Medicine, ISSN 1471-2466, E-ISSN 1471-2466, Vol. 19, artikel-id 50Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: Long-term oxygen therapy (LTOT) during 15h/day or more prolongs survival in patients with chronic obstructive pulmonary disease (COPD) and severe hypoxemia. No randomized controlled trial has evaluated the net effects (benefits or harms) from LTOT 24h/day compared with 15h/day or the effect in conditions other than COPD. We describe a multicenter, national, phase IV, non-superiority, registry-based, randomized controlled trial (R-RCT) of LTOT prescribed 24h/day compared with 15h/day. The primary endpoint is all-cause-mortality at 1year. Secondary endpoints include cause-specific mortality, hospitalizations, health-related quality of life, symptoms, and outcomes in interstitial lung disease. Methods/design: Patients qualifying for LTOT are randomized to LTOT 24h/day versus 15h/day during 12months using the Swedish Register for Respiratory Failure (Swedevox). Planned sample size in this pragmatic study is 2126 randomized patients. Clinical follow-up and concurrent treatments are according to routine clinical practice. Mortality, hospitalizations, and incident diseases are assessed using national Swedish registries with expected complete follow-up. Patient-reported outcomes are assessed using postal questionnaire at 3 and 12months. Discussion: The R-RCT approach combines the advantages of a prospective randomized trial and large clinical national registries for enrollment, allocation, and data collection, with the aim of improving the evidence-based use of LTOT. Trial registration: Clinical Trial registered with www.clinicaltrials.gov, Title: REgistry-based Treatment Duration and Mortality in Long-term OXygen Therapy (REDOX); ID: NCT03441204.

  • 128.
    Söderberg, Stefan
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Ahlström, Håkan
    Blomberg, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Brandberg, John
    Caidahl, Kenneth
    Cederlund, Kerstin
    Engström, Gunnar
    Engvall, Jan
    Fagman, Erika
    Franklin, Karl A
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap.
    Hansen, Tomas
    Hedblad, Bo
    Hjelmgren, Ola
    Jernberg, Tomas
    Lind, Lars
    Markstad, Hanna
    Nilsson, Lars T.
    Persson, Anders
    Persson, Margaretha
    Rosengren, Annika
    Skold, Magnus
    Sundstrom, Johan
    Swahn, Eva
    Stromberg, Ulf
    Ostgren, Carl Johan
    MEASURES OF WAIST AND HIP MODIFY SEX-SPECIFIC ASSOCIATIONS BETWEEN BODY MASS INDEX AND PREVALENCE OF CORONARY ARTERY CALCIFICATION IN OPPOSITE DIRECTIONS2019Ingår i: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 73, nr 9, s. 13-13Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Background: Obesity is associated with increased risk of cardiovascular disease. However, there is still a debate whether accumulation of fat in certain depots modifies this risk. Using data from the CArdioPulmonary bioImage Study (SCAPIS), we investigated if anthropometric measurements of obesity (waist and hip) modifies the risk of coronary artery calcification. Methods: In the first 15,810 participants in SCAPIS (mean age 58 years, 52% women), data on coronary artery calcification score (CACS) and anthropometry were recorded and traditional cardiovascular risk factors were measured. Body mass index (BMI) was categorized as; <25, 25-30, 30-35 and >35 kg/m2 , quartiles of waist and hip circumferences were constructed within each BMI category and compared using the lowest quartile as reference. Results were adjusted for site, age, smoking and diabetes status. Results: Obesity (BMI >30 kg/m2 ) was found in 21.9% of men and in 20.5% of women. In both sexes the odds ratio (OR) for CACS >0 increased with increasing BMI categories: comparing <25 and >35 kg/m2 , OR = 2.1 (95% CI: 1.6-2.7) for men and OR = 1.4 (1.2-1.8) for women. In addition, increasing quartiles of waist significantly increased the prevalence of CACS >0 for men [p = 0.05; OR = 1.2 (1.0-1.4) for highest quartile] and women [p = 0.005; OR = 1.3 (1.1-1.5)] while increasing quartiles of hip significantly decreased the prevalence for men [p = 0.005; OR = 0.8 (0.6-0.9)] and women [p = 0.04; OR = 0.8 (0.7-0.9)]. Data on education level and physical activity did not affect the model. Conclusion: Increased BMI is associated with increased prevalence of coronary artery calcification and the distribution of fat modifies this risk. Our results suggest that gluteofemoral adipose tissue (hip) counteracts the negative effects associated with BMI and abdominal adipose tissue (waist).

  • 129. Tariq, K.
    et al.
    Schofield, J. P. R.
    Nicholas, B. L.
    Burg, D.
    Brandsma, J.
    Bansal, A. T.
    Wilson, S. J.
    Lutter, R.
    Fowler, S. J.
    Bakke, .
    Caruso, M.
    Dahlen, B.
    Horvath, I.
    Krug, N.
    Montuschi, P.
    Sanak, M.
    Sandström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin. Respiratory Medicine Unit, Umeå University, Umeå, Sweden.
    Geiser, T.
    Pandis, I.
    Sousa, A. R.
    Adcock, I. M.
    Shaw, D. E.
    Auffray, C.
    Howarth, P. H.
    Sterk, P. J.
    Chung, K. F.
    Skipp, P. J.
    Dimitrov, B.
    Djukanovic, R.
    Sputum proteomic signature of gastro-oesophageal reflux in patients with severe asthma2019Ingår i: Respiratory Medicine, ISSN 0954-6111, E-ISSN 1532-3064, Vol. 150, s. 66-73Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Gastro-oesophageal reflux disease (GORD) has long been associated with poor asthma control without an established cause-effect relationship. 610 asthmatics (421 severe/88 mild-moderate) and 101 healthy controls were assessed clinically and a subset of 154 severe asthmatics underwent proteomic analysis of induced sputum using untargeted mass spectrometry, LC-IMS-MSE. Univariate and multiple logistic regression analyses (MLR) were conducted to identify proteins associated with GORD in this cohort. When compared to mild/moderate asthmatics and healthy individuals, respectively, GORD was three-and ten-fold more prevalent in severe asthmatics and was associated with increased asthma symptoms and oral corticosteroid use, poorer quality of life, depression/anxiety, obesity and symptoms of sino-nasal disease. Comparison of sputum proteomes in severe asthmatics with and without active GORD showed five differentially abundant proteins with described roles in antimicrobial defences, systemic inflammation and epithelial integrity. Three of these were associated with active GORD by multiple linear regression analysis: Ig lambda variable 1-47 (p = 0.017) and plasma protease C1 inhibitor (p = 0.043), both in lower concentrations, and lipocalin-1 (p = 0.034) in higher concentrations in active GORD. This study provides evidence which suggests that reflux can cause subtle perturbation of proteins detectable in the airways lining fluid and that severe asthmatics with GORD may represent a distinct phenotype of asthma.

  • 130.
    Thornberg, Evelina
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Incidence, etiology and risk factors of traumatic spinal cord injury in Northern Sweden2018Självständigt arbete på grundnivå (yrkesexamen), 20 poäng / 30 hpStudentuppsats (Examensarbete)
  • 131.
    Toots, Annika
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Fysioterapi. Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Littbrand, Håkan
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Fysioterapi. Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Boström, Gustaf
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Hörnsten, Carl
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Holmberg, Henrik
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Lundin-Olsson, Lillemor
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Fysioterapi.
    Lindelöf, Nina
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Fysioterapi. Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Nordström, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Gustafson, Yngve
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Rosendahl, Erik
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Fysioterapi. Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Effects of exercise on cognitive function in older people with dementia: a randomized controlled trial2017Ingår i: Journal of alzheimers disease, ISSN 1387-2877, Vol. 60, nr 1, s. 323-332Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Although physical exercise has been suggested to influence cognitive function, previous exercise studies show inconsistent results in people with dementia. Objectives: To investigate effects of exercise on cognitive function in people with dementia. Method: The Umea a Dementia and Exercise (UMDEX) study, a cluster-randomized controlled trial, was set in 16 nursing homes in Umea, Sweden. One hundred-and-forty-one women and 45 men with dementia; mean age of 85 y and mean MiniMental State Examination (MMSE) score of 15, were randomized to a High-Intensity Functional Exercise program or a seated attention control activity. Blinded assessors measured global cognitive function using the MMSE and the Alzheimer's disease Assessment Scale -Cognitive subscale (ADAS-Cog), and executive function using Verbal fluency (VF) at baseline and 4 months (directly after intervention completion), and MMSE and VF at 7 months. Results: Linear mixed models showed no between-group effects in mean difference from baseline (95% confidence intervals, CI) at 4 months in MMSE (-0.27; 95% CI -1.4 to 0.87, p = 0.644), ADAS-Cog (-1.04, 95% CI -4 to 1.92, p = 0.491), or VF (-0.53, 95% CI -1.42 to 0.35, p = 0.241) or at 7 months in MMSE (-1.15, 95% CI -2.32 to 0.03, p = 0.056) or VF (-0.18, 95% CI -1.09 to 0.74, p = 0.707). Conclusion: A 4-month, high-intensity functional exercise program had no superior effects on global cognition or executive function in people with dementia living in nursing homes when compared with an attention control activity.

  • 132.
    Toots, Annika
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Fysioterapi. Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Littbrand, Håkan
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Fysioterapi. Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Holmberg, Henrik
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Nordström, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Lundin-Olsson, Lillemor
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Fysioterapi.
    Gustafson, Yngve
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Rosendahl, Erik
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Fysioterapi. Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Walking aids moderate exercise effects on gait speed in people with dementia: a randomized controlled trial2017Ingår i: Journal of the American Medical Directors Association, ISSN 1525-8610, E-ISSN 1538-9375, Vol. 18, nr 3, s. 227-233Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVES: To investigate the effects of exercise on gait speed, when tested using walking aids and without, and whether effects differed according to amount of support in the test.

    DESIGN: A cluster-randomized controlled trial.

    SETTING: The Umeå Dementia and Exercise (UMDEX) study was set in 16 nursing homes in Umeå, Sweden.

    PARTICIPANTS: One hundred forty-one women and 45 men (mean age 85 years) with dementia, of whom 145 (78%) habitually used walking aids.

    INTERVENTION: Participants were randomized to the high-intensity functional exercise program or a seated attention control activity.

    MEASUREMENTS: Blinded assessors measured 4-m usual gait speed with walking aids if any gait speed (GS), and without walking aids and with minimum amount of support, at baseline, 4 months (on intervention completion), and 7 months.

    RESULTS: Linear mixed models showed no between-group effect in either gait speed test at 4 or 7 months. In interaction analyses exercise effects differed significantly between participants who walked unsupported compared with when walking aids or minimum support was used. Positive between-group exercise effects on gait speed (m/s) were found in subgroups that walked unsupported at 4 and 7 months (GS: 0.07, P = .009 and 0.13, P < .001; and GS test without walking aids: 0.05, P = .011 and 0.07, P = .029, respectively).

    CONCLUSIONS: In people with dementia living in nursing homes exercise had positive effects on gait when tested unsupported compared with when walking aids or minimum support was used. The study suggests that the use of walking aids in gait speed tests may conceal exercise effects.

  • 133.
    Toots, Annika
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik. Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Fysioterapi.
    Littbrand, Håkan
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik. Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Fysioterapi.
    Lindelöf, Nina
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik. Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Fysioterapi.
    Wiklund, Robert
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik. Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Fysioterapi.
    Holmberg, Henrik
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Nordström, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Lundin-Olsson, Lillemor
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Fysioterapi.
    Gustafson, Yngve
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Rosendahl, Erik
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik. Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Fysioterapi.
    Effects of a High-Intensity Functional Exercise Program on Dependence in Activities of Daily Living and Balance in Older Adults with Dementia2016Ingår i: Journal of The American Geriatrics Society, ISSN 0002-8614, E-ISSN 1532-5415, Vol. 64, nr 1, s. 55-64Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVES: To investigate the effects of a high-intensity functional exercise program on independence in activities of  daily living (ADLs) and balance in older people with dementia and whether exercise effects differed between dementia types.

    DESIGN: Cluster-randomized controlled trial: Umeå Dementia and Exercise (UMDEX) study.

    SETTING: Residential care facilities, Umeå, Sweden.

    PARTICIPANTS: Individuals aged 65 and older with a dementia diagnosis, a Mini-Mental State Examination score of 10 or greater, and dependence in ADLs (N = 186).

    INTERVENTION: Ninety-three participants each were allocated to the high-intensity functional exercise program, comprising lower limb strength and balance exercises, and 93 to a seated control activity.

    MEASUREMENTS: Blinded assessors measured ADL independence using the Functional Independence Measure (FIM) and Barthel Index (BI) and balance using the Berg Balance Scale (BBS) at baseline and 4 (directly after intervention completion) and 7 months.

    RESULTS: Linear mixed models showed no between-group effect on ADL independence at 4 (FIM=1.3, 95% confidence interval (CI)=-1.6-4.3; BI=0.6, 95% CI=-0.2-1.4) or 7 (FIM=0.8, 95% CI=-2.2-3.8; BI=0.6, 95% CI=-0.3-1.4) months. A significant between-group effect on balance favoring exercise was observed at 4 months (BBS=4.2, 95% CI=1.8-6.6). In interaction analyses, exercise effects differed significantly between dementia types. Positive between-group exercise effects were found in participants with non-Alzheimer's dementia according to the FIM at 7 months and BI and BBS at 4 and 7 months.

    CONCLUSION: In older people with mild to moderate dementia living in residential care facilities, a 4-month high-intensity functional exercise program appears to slow decline in ADL independence and improve balance, albeit only in participants with non-Alzheimer's dementia.

  • 134. Turcot, Valerie
    et al.
    Lu, Yingchang
    Highland, Heather M.
    Schurmann, Claudia
    Justice, Anne E.
    Fine, Rebecca S.
    Bradfield, Jonathan P.
    Esko, Tonu
    Giri, Ayush
    Graff, Mariaelisa
    Guo, Xiuqing
    Hendricks, Audrey E.
    Karaderi, Tugce
    Lempradl, Adelheid
    Locke, Adam E.
    Mahajan, Anubha
    Marouli, Eirini
    Sivapalaratnam, Suthesh
    Young, Kristin L.
    Alfred, Tamuno
    Feitosa, Mary F.
    Masca, Nicholas G. D.
    Manning, Alisa K.
    Medina-Gomez, Carolina
    Mudgal, Poorva
    Ng, Maggie C. Y.
    Reiner, Alex P.
    Vedantam, Sailaja
    Willems, Sara M.
    Winkler, Thomas W.
    Abecasis, Goncalo
    Aben, Katja K.
    Alam, Dewan S.
    Alharthi, Sameer E.
    Allison, Matthew
    Amouyel, Philippe
    Asselbergs, Folkert W.
    Auer, Paul L.
    Balkau, Beverley
    Bang, Lia E.
    Barroso, Ines
    Bastarache, Lisa
    Benn, Marianne
    Bergmann, Sven
    Bielak, Lawrence F.
    Blueher, Matthias
    Boehnke, Michael
    Boeing, Heiner
    Boerwinkle, Eric
    Boeger, Carsten A.
    Bork-Jensen, Jette
    Bots, Michiel L.
    Bottinger, Erwin P.
    Bowden, Donald W.
    Brandslund, Ivan
    Breen, Gerome
    Brilliant, Murray H.
    Broer, Linda
    Brumat, Marco
    Burt, Amber A.
    Butterworth, Adam S.
    Campbell, Peter T.
    Cappellani, Stefania
    Carey, David J.
    Catamo, Eulalia
    Caulfield, Mark J.
    Chambers, John C.
    Chasman, Daniel I.
    Chen, Yii-Der I.
    Chowdhury, Rajiv
    Christensen, Cramer
    Chu, Audrey Y.
    Cocca, Massimiliano
    Collins, Francis S.
    Cook, James P.
    Corley, Janie
    Galbany, Jordi Corominas
    Cox, Amanda J.
    Crosslin, David S.
    Cuellar-Partida, Gabriel
    D'Eustacchio, Angela
    Danesh, John
    Davies, Gail
    Bakker, Paul I. W.
    Groot, Mark C. H.
    Mutsert, Renee
    Deary, Ian J.
    Dedoussis, George
    Demerath, Ellen W.
    Heijer, Martin
    Hollander, Anneke I.
    Ruijter, Hester M.
    Dennis, Joe G.
    Denny, Josh C.
    Angelantonio, Emanuele
    Drenos, Fotios
    Du, Mengmeng
    Dube, Marie-Pierre
    Dunning, Alison M.
    Easton, Douglas F.
    Edwards, Todd L.
    Ellinghaus, David
    Ellinor, Patrick T.
    Elliott, Paul
    Evangelou, Evangelos
    Farmaki, Aliki-Eleni
    Farooqi, I. Sadaf
    Faul, Jessica D.
    Fauser, Sascha
    Feng, Shuang
    Ferrannini, Ele
    Ferrieres, Jean
    Florez, Jose C.
    Ford, Ian
    Fornage, Myriam
    Franco, Oscar H.
    Franke, Andre
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Malmö, Sweden; Department of Nutrition, Harvard School of Public Health, Boston, MA, USA.
    Friedrich, Nele
    Frikke-Schmidt, Ruth
    Galesloot, Tessel E.
    Gan, Wei
    Gandin, Ilaria
    Gasparini, Paolo
    Gibson, Jane
    Giedraitis, Vilmantas
    Gjesing, Anette P.
    Gordon-Larsen, Penny
    Gorski, Mathias
    Grabe, Hans-Joergen
    Grant, Struan F. A.
    Grarup, Niels
    Griffiths, Helen L.
    Grove, Megan L.
    Gudnason, Vilmundur
    Gustafsson, Stefan
    Haessler, Jeff
    Hakonarson, Hakon
    Hammerschlag, Anke R.
    Hansen, Torben
    Harris, Kathleen Mullan
    Harris, Tamara B.
    Hattersley, Andrew T.
    Have, Christian T.
    Hayward, Caroline
    He, Liang
    Heard-Costa, Nancy L.
    Heath, Andrew C.
    Heid, Iris M.
    Helgeland, Oyvind
    Hernesniemi, Jussi
    Hewitt, Alex W.
    Holmen, Oddgeir L.
    Hovingh, G. Kees
    Howson, Joanna M. M.
    Hu, Yao
    Huang, Paul L.
    Huffman, Jennifer E.
    Ikram, M. Arfan
    Ingelsson, Erik
    Jackson, Anne U.
    Jansson, Jan-Håkan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin. Research Unit Skellefteå, Skellefteå, Sweden.
    Jarvik, Gail P.
    Jensen, Gorm B.
    Jia, Yucheng
    Johansson, Stefan
    Jorgensen, Marit E.
    Jorgensen, Torben
    Jukema, J. Wouter
    Kahali, Bratati
    Kahn, Rene S.
    Kahonen, Mika
    Kamstrup, Pia R.
    Kanoni, Stavroula
    Kaprio, Jaakko
    Karaleftheri, Maria
    Kardia, Sharon L. R.
    Karpe, Fredrik
    Kathiresan, Sekar
    Kee, Frank
    Kiemeney, Lambertus A.
    Kim, Eric
    Kitajima, Hidetoshi
    Komulainen, Pirjo
    Kooner, Jaspal S.
    Kooperberg, Charles
    Korhonen, Tellervo
    Kovacs, Peter
    Kuivaniemi, Helena
    Kutalik, Zoltan
    Kuulasmaa, Kari
    Kuusisto, Johanna
    Laakso, Markku
    Lakka, Timo A.
    Lamparter, David
    Lange, Ethan M.
    Lange, Leslie A.
    Langenberg, Claudia
    Larson, Eric B.
    Lee, Nanette R.
    Lehtimaki, Terho
    Lewis, Cora E.
    Li, Huaixing
    Li, Jin
    Li-Gao, Ruifang
    Lin, Honghuang
    Lin, Keng-Hung
    Lin, Li-An
    Lin, Xu
    Lind, Lars
    Lindstrom, Jaana
    Linneberg, Allan
    Liu, Ching-Ti
    Liu, Dajiang J.
    Liu, Yongmei
    Lo, Ken S.
    Lophatananon, Artitaya
    Lotery, Andrew J.
    Loukola, Anu
    Luan, Jian'an
    Lubitz, Steven A.
    Lyytikainen, Leo-Pekka
    Mannisto, Satu
    Marenne, Gaelle
    Mazul, Angela L.
    McCarthy, Mark I.
    McKean-Cowdin, Roberta
    Medland, Sarah E.
    Meidtner, Karina
    Milani, Lili
    Mistry, Vanisha
    Mitchell, Paul
    Mohlke, Karen L.
    Moilanen, Leena
    Moitry, Marie
    Montgomery, Grant W.
    Mook-Kanamori, Dennis O.
    Moore, Carmel
    Mori, Trevor A.
    Morris, Andrew D.
    Morris, Andrew P.
    Mueller-Nurasyid, Martina
    Munroe, Patricia B.
    Nalls, Mike A.
    Narisu, Narisu
    Nelson, Christopher P.
    Neville, Matt
    Nielsen, Sune F.
    Nikus, Kjell
    Njolstad, Pal R.
    Nordestgaard, Borge G.
    Nyholt, Dale R.
    O'Connel, Jeffrey R.
    O'Donoghue, Michelle L.
    Loohuis, Loes M. Olde
    Ophoff, Roel A.
    Owen, Katharine R.
    Packard, Chris J.
    Padmanabhan, Sandosh
    Palmer, Colin N. A.
    Palmer, Nicholette D.
    Pasterkamp, Gerard
    Patel, Aniruddh P.
    Pattie, Alison
    Pedersen, Oluf
    Peissig, Peggy L.
    Peloso, Gina M.
    Pennell, Craig E.
    Perola, Markus
    Perry, James A.
    Perry, John R. B.
    Pers, Tune H.
    Person, Thomas N.
    Peters, Annette
    Petersen, Eva R. B.
    Peyser, Patricia A.
    Pirie, Ailith
    Polasek, Ozren
    Polderman, Tinca J.
    Puolijoki, Hannu
    Raitakari, Olli T.
    Rasheed, Asif
    Rauramaa, Rainer
    Reilly, Dermot F.
    Renström, Frida
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning. Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Malmö, Sweden.
    Rheinberger, Myriam
    Ridker, Paul M.
    Rioux, John D.
    Rivas, Manuel A.
    Roberts, David J.
    Robertson, Neil R.
    Robino, Antonietta
    Rolandsson, Olov
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Rudan, Igor
    Ruth, Katherine S.
    Saleheen, Danish
    Salomaa, Veikko
    Samani, Nilesh J.
    Sapkota, Yadav
    Sattar, Naveed
    Schoen, Robert E.
    Schreiner, Pamela J.
    Schulze, Matthias B.
    Scott, Robert A.
    Segura-Lepe, Marcelo P.
    Shah, Svati H.
    Sheu, Wayne H. -H.
    Sim, Xueling
    Slater, Andrew J.
    Small, Kerrin S.
    Smith, Albert V.
    Southam, Lorraine
    Spector, Timothy D.
    Speliotes, Elizabeth K.
    Starr, John M.
    Stefansson, Kari
    Steinthorsdottir, Valgerdur
    Stirrups, Kathleen E.
    Strauch, Konstantin
    Stringham, Heather M.
    Stumvoll, Michael
    Sun, Liang
    Surendran, Praveen
    Swift, Amy J.
    Tada, Hayato
    Tansey, Katherine E.
    Tardif, Jean-Claude
    Taylor, Kent D.
    Teumer, Alexander
    Thompson, Deborah J.
    Thorleifsson, Gudmar
    Thorsteinsdottir, Unnur
    Thuesen, Betina H.
    Toenjes, Anke
    Tromp, Gerard
    Trompet, Stella
    Tsafantakis, Emmanouil
    Tuomilehto, Jaakko
    Tybjaerg-Hansen, Anne
    Tyrer, Jonathan P.
    Uher, Rudolf
    Uitterlinden, Andre G.
    Uusitupa, Matti
    Laan, Sander W.
    Duijn, Cornelia M.
    Leeuwen, Nienke
    van Setten, Jessica
    Vanhala, Mauno
    Varbo, Anette
    Varga, Tibor V.
    Varma, Rohit
    Edwards, Digna R. Velez
    Vermeulen, Sita H.
    Veronesi, Giovanni
    Vestergaard, Henrik
    Vitart, Veronique
    Vogt, Thomas F.
    Voelker, Uwe
    Vuckovic, Dragana
    Wagenknecht, Lynne E.
    Walker, Mark
    Wallentin, Lars
    Wang, Feijie
    Wang, Carol A.
    Wang, Shuai
    Wang, Yiqin
    Ware, Erin B.
    Wareham, Nicholas J.
    Warren, Helen R.
    Waterworth, Dawn M.
    Wessel, Jennifer
    White, Harvey D.
    Willer, Cristen J.
    Wilson, James G.
    Witte, Daniel R.
    Wood, Andrew R.
    Wu, Ying
    Yaghootkar, Hanieh
    Yao, Jie
    Yao, Pang
    Yerges-Armstrong, Laura M.
    Young, Robin
    Zeggini, Eleftheria
    Zhan, Xiaowei
    Zhang, Weihua
    Zhao, Jing Hua
    Zhao, Wei
    Zhou, Wei
    Zondervan, Krina T.
    Rotter, Jerome I.
    Pospisilik, John A.
    Rivadeneira, Fernando
    Borecki, Ingrid B.
    Deloukas, Panos
    Frayling, Timothy M.
    Lettre, Guillaume
    North, Kari E.
    Lindgren, Cecilia M.
    Hirschhorn, Joel N.
    Loos, Ruth J. F.
    Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity2018Ingår i: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 50, nr 1, s. 26-41Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are similar to 10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed similar to 7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity.

  • 135. Ueland, Grethe Å.
    et al.
    Methlie, Paal
    Øksnes, Marianne
    Thordarson, Hrafnkell B.
    Sagen, Jørn
    Kellmann, Ralf
    Mellgren, Gunnar
    Ræder, Maria
    Dahlqvist, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Dahl, Sandra R.
    Thorsby, Per M.
    Løvås, Kristian
    Husebye, Eystein S.
    The Short Cosyntropin Test Revisited: New Normal Reference Range Using LC-MS/MS2018Ingår i: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 103, nr 4, s. 1696-1703Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The cosyntropin test is used to diagnose adrenal insufficiency (AI) and nonclassical congenital adrenal hyperplasia (NCCAH). Current cutoffs for cortisol and 17-hydroxyprogesterone (17-OHP) are derived from nonstandardized immunoassays. Liquid chromatography tandem mass spectrometry (LC-MS/MS) offers direct measurement of steroids, prompting the need to re-establish normal ranges. Objective: The goal of this study was to define cutoff values for cortisol and 17-OHP in serum by LC-MS/MS 30 and 60 minutes after intravenous administration of 250 µg tetracosactide acetate to healthy volunteers and to compare the results with LC-MS/MS with routine immunoassays. Methods: Cosyntropin testing was performed in healthy subjects (n = 138) and in patients referred for evaluation of adrenocortical function (n = 94). Steroids were assayed by LC-MS/MS and compared with two immunoassays used in routine diagnostics (Immulite and Roche platforms). The cutoff level for cortisol was defined as the 2.5% percentile in healthy subjects not using oral estrogens (n = 121) and for 17-OHP as the 97.5% percentile. Results: Cortisol cutoff levels for LC-MS/MS were 412 and 485 nmol/L at 30 and 60 minutes, respectively. Applying the new cutoffs, 13 of 60 (22%) subjects who had AI according to conventional criteria now had a normal test result. For 17-OHP, the cutoff levels were 8.9 and 9.0 nmol/L at 30 and 60 minutes, respectively. Conclusions: LC-MS/MS provides cutoff levels for cortisol and 17-OHP after cosyntropin stimulation that are lower than those based on immunoassays, possibly because cross-reactivity between steroid intermediates and cortisol is eliminated. This reduces the number of false-positive tests for AI and false-negative tests for NCCAH.

  • 136.
    Ulvenstam, Anders
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Unit of Research, Education and Development, Östersund Hospital, Sweden.
    Henriksson, Robin
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Söderström, Lars
    Mooe, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Ischemic stroke rates decrease with increased ticagrelor use after acute myocardial infarction in patients treated with percutaneous coronary intervention2018Ingår i: European Journal of Preventive Cardiology, ISSN 2047-4873, E-ISSN 2047-4881, Vol. 25, nr 11, s. 1219-1230Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aims: It is unknown whether dual antiplatelet therapy with ticagrelor instead of clopidogrel reduces the risk of ischaemic stroke in acute myocardial infarction patients that undergo percutaneous coronary intervention. This study investigated whether the introduction of dual antiplatelet therapy with ticagrelor was associated with reduced ischaemic stroke risk in a real-world population.

    Methods and results: Patients with ischaemic stroke after acute myocardial infarction from 8 December 2009-31 December 2013 were identified using the Register for Information and Knowledge on Swedish Heart Intensive Care Admissions and the Swedish National Patient Register. The study period was divided into two similar periods using the date of the first prescription of ticagrelor as the cut-off. The risk of ischaemic stroke in percutaneous coronary intervention-treated acute myocardial infarction patients during the first period (100% clopidogrel treatment) versus the second period (60.7% ticagrelor treatment) was assessed using Kaplan-Meier analysis. Variables associated with ischaemic stroke were identified using a multivariable Cox proportional hazards model. There were 686 ischaemic stroke events (2.0%) among 34931 percutaneous coronary intervention-treated acute myocardial infarction patients within one year, 366 (2.2%) during the first period and 320 (1.8%) during the second period (p=0.004). The Cox model showed a 21% relative risk reduction in ischaemic stroke in the second period versus the first one (hazard ratio 0.79, 95% confidence interval, 0.68-0.92; p=0.003). The independent predictors of increased stroke risk were older age, hypertension, diabetes mellitus, atrial fibrillation, heart failure during hospitalization, previous ischaemic stroke, and ST-segment elevation myocardial infarction.

    Conclusion: The risk of ischaemic stroke in percutaneous coronary intervention-treated acute myocardial infarction patients decreased after the introduction of ticagrelor in Sweden.

  • 137.
    Vouzouneraki, Konstantina
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Franklin, Karl A
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Forsgren, Maria
    Wärn, Maria
    Persson, Jenny Tiberg
    Wik, Helena
    Dahlgren, Christina
    Nilsson, Ann-Sofie
    Alkebro, Caroline
    Burman, Pia
    Erfurth, Eva-Marie
    Wahlberg, Jeanette
    Åkerman, Anna-Karin
    Høbye, Charlotte
    Ragnarsson, Oskar
    Edén Engström, Britt
    Dahlqvist, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Temporal relationship of sleep apnea and acromegaly: a nationwide study2018Ingår i: Endocrine (Basingstoke), ISSN 1355-008X, E-ISSN 1559-0100, Vol. 62, nr 2, s. 456-463Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose:

    Patients with acromegaly have an increased risk of sleep apnea, but reported prevalence rates vary largely. Here we aimed to evaluate the sleep apnea prevalence in a large national cohort of patients with acromegaly, to examine possible risk factors, and to assess the proportion of patients diagnosed with sleep apnea prior to acromegaly diagnosis.

    Methods: Cross-sectional multicenter study of 259 Swedish patients with acromegaly. At patients' follow-up visits at the endocrine outpatient clinics of all seven university hospitals in Sweden, questionnaires were completed to assess previous sleep apnea diagnosis and treatment, cardiovascular diseases, smoking habits, anthropometric data, and S-IGF-1 levels. Daytime sleepiness was evaluated using the Epworth Sleepiness Scale. Patients suspected to have undiagnosed sleep apnea were referred for sleep apnea investigations.

    Results: Of the 259 participants, 75 (29%) were diagnosed with sleep apnea before the study start. In 43 (57%) of these patients, sleep apnea had been diagnosed before the diagnosis of acromegaly. After clinical assessment and sleep studies, sleep apnea was diagnosed in an additional 20 patients, yielding a total sleep apnea prevalence of 37%. Higher sleep apnea risk was associated with higher BMI, waist circumference, and index finger circumference. Sleep apnea was more frequent among patients with S-IGF-1 levels in the highest quartile.

    Conclusion: Sleep apnea is common among patients with acromegaly, and is often diagnosed prior to their acromegaly diagnosis. These results support early screening for sleep apnea in patients with acromegaly and awareness for acromegaly in patients with sleep apnea.

  • 138.
    Wadell, Daniel
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Jensen, Jens
    Englund, Erling
    Själander, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Triple therapy after PCI - Warfarin treatment quality and bleeding risk2018Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, nr 12, artikel-id e0209187Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: A combination of warfarin, aspirin and clopidogrel is indicated after percutaneous coronary intervention (PCI) in some patients, despite the higher risk of bleeding inferred by this triple therapy.

    Objectives: Whether the treatment quality of warfarin measured by iTTR (individual time within therapeutic INR range) is associated with bleeding complications during triple therapy after PCI.

    Methods: A retrospective register study consisting of 601 triple treated PCI patients from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR). The cohort was cross-matched with the Swedish Patient Registry for background characteristics and bleeding complications up to 6 months after PCI using ICD10 codes, the Prescribed Drug Registry for ongoing medications, and the national oral anticoagulation registry Auricula for warfarin treatment quality. The patients were grouped into four iTTR groups: <50%, 50–69.9%, 70–84.9% and >85% as well as iTTR above or below 70%.

    Results: Of 601 patients, 39 (6.5%) had a bleeding complication (type 2 according to BARC). Bleeding was more common for iTTR<70% compared to iTTR>70%, 28 (9.3%) vs. 11 (3.7%) (p = 0.005). The bleeding frequency increased gradually from the best group, iTTR>85% with four bleeders (3.3%) up to 17 bleeders (13.3%) in the worst group with iTTR<50% (p = 0.003), with a corresponding bleeding rate per 100 treatment years of 8.0 and 44.9, respectively. In multivariate analysis low BMI, HR 1.11 (95% CI 1.01–1.22), a medical history of anemia HR 3.17 (1.16–8.69) and iTTR < 70% HR 2.86 (1.25–6.53) increased the risk of bleeding.

    Conclusion: Triple therapy after PCI confers a high risk of bleeding events. Warfarin treatment quality measured by iTTR as well as a medical history of anemia are strong independent predictors of bleeding in these patients. Physicians should pay more attention to iTTR after PCI.

  • 139.
    Wange, Niklas
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Anan, Intissar
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Ericzon, Bo-Göran
    Pennlert, Johanna
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Pilebro, Björn
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Suhr, Ole B.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Wixner, Jonas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Atrial Fibrillation and Central Nervous Complications in Liver Transplanted Hereditary Transthyretin Amyloidosis Patients2018Ingår i: Transplantation, ISSN 0041-1337, E-ISSN 1534-6080, Vol. 102, nr 2, s. e59-e66Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background. Central nervous system (CNS) complications are increasingly noted in liver transplanted (LTx) hereditary transthyretin amyloid (ATTRm) amyloidosis patients; this suggests that the increased survival allows for intracranial ATTRm formation from brain synthesized mutant TTR. However, atrial fibrillation (AF), a recognised risk factor for ischemic CNS complications, is also observed after LTx. The aim of the study was to investigate the occurrence of CNS complications and AF in LTx ATTRm amyloidosis patients. Methods. The medical records of all LTx ATTRm amyloidosis patients in the county of Vasterbotten, Sweden, were investigated for information on CNS complications, AF, anticoagulation (AC) therapy, hypertension, cardiac ischemic disease, hypertrophy, and neurological status. Results. Sixty-three patients that had survived for 3 years or longer after LTx were included in the analysis. Twenty-five patients had developed 1 or more CNS complications at a median of 21 years after onset of disease. AF was noted in 21 patients (median time to diagnosis 24 years). Cerebrovascular events (CVE) developed in 17 (median time to event 21 years). CVEs occurred significantly more often in patients with AF (P < 0.002). AC therapy significantly reduced CVEs, including bleeding in patients with AF (P = 0.04). Multivariate analysis identified AF as the only remaining regressor with a significant impact on CVE (hazard ratio, 3.8; 95% confidence interval 1.1-9.5; P = 0.029). Conclusions. AF is an important risk factor for CVE in LTx ATTRm amyloidosis patients, and AC therapy should be considered. However, the increased bleeding risk with AC therapy in patients with intracranial amyloidosis should be acknowledged.

  • 140.
    Wiklund, Robert
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik. Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Fysioterapi.
    Toots, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik. Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Fysioterapi.
    Conradsson, Mia
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Olofsson, Birgitta
    Umeå universitet, Medicinska fakulteten, Institutionen för omvårdnad. Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi.
    Holmberg, Henrik
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Rosendahl, Erik
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Fysioterapi. Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Gustafson, Yngve
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Littbrand, Håkan
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik. Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Fysioterapi.
    Risk factors for hip fracture in very old people: a population-based study2016Ingår i: Osteoporosis International, ISSN 0937-941X, E-ISSN 1433-2965, Vol. 27, nr 3, s. 923-931Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Knowledge of risk factors for hip fracture among very old people is limited. Walking indoors with help from ≤1 person, Parkinson's disease, currently smoking, delirium in the previous month, underweight, and age were associated with increased risk of hip fracture and could be important for preventive strategy development.

    INTRODUCTION: The purpose of this study is to investigate risk factors for hip fracture among a representative sample of very old people.

    METHODS: In total, 953 participants from the Umeå 85+/Gerontological Regional Database population-based cohort study were interviewed and assessed during home visits. Associations of baseline characteristics with hip fracture during the maximum 5-year follow-up period were analyzed using Cox proportional hazards regression.

    RESULTS: Participants had a mean age of 89.3 ± 4.7 years; 65.8 % were women, 36.8 % lived in residential care facilities, 33.6 % had dementia, and 20.4 % had histories of hip fracture. During a mean follow-up period of 2.7 years, 96 (10.1 %) individuals sustained hip fracture. Walking indoors with help from no more than one person (hazard ratio [HR] = 8.57; 95 % confidence interval [CI], 1.90-38.71), Parkinson's disease (HR = 5.12; 95 % CI, 1.82-14.44), currently smoking (HR = 4.38; 95 % CI 2.06-9.33), delirium in the previous month (HR = 2.01; 95 % CI, 1.15-3.49), underweight (body mass index <22; HR = 1.74, 95 % CI, 1.09-2.77), and age (HR = 1.09; 95 % CI, 1.04-1.14) were associated independently with an increased risk of hip fracture. Hip prosthesis at baseline decreased the risk of hip fracture (HR = 0.37; 95 % CI, 0.15-0.91), but only for those with bilateral hip prostheses.

    CONCLUSIONS: Seven factors were associated independently with incident hip fracture during follow-up in this sample of very old people. These factors could have important clinical implications in identifying persons at high risk of hip fracture, as well as in the development of effective preventive strategies.

  • 141.
    Wiklund, Urban
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Kadkhodaee, Amir
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Andersson, Kennet
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Suhr, Ole B.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Hörnsten, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Klinisk fysiologi.
    Normal scores of deep breathing tests: beware of dysrhythmia in transthyretin amyloidosis2018Ingår i: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 25, nr 1, s. 54-61Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The heart rate (HR) response to paced deep breathing (DB) is a common test of cardiac autonomic function, where high heart rate variability (HRV) is considered to reflect normal autonomic function. We evaluated the DB test in patients with hereditary transthyretin amyloid (ATTRm) amyloidosis, where autonomic dysregulation and atrial arrhythmias are common.Methods: Paced DB was performed during one minute (six breaths/min) in 165 recordings in adult ATTRm amyloidosis patients with the TTR Val30Met mutation, 42 hypertrophic cardiomyopathy (HCM) patients and 211 healthy subjects. HRV was scored by traditional DB indices and by a novel regularity index, estimating the fraction of the HRV that was coherent with the breathing pattern.Results: Twenty per cent of ATTRm amyloidosis patients presented with age-adjusted HRV scores within normal limits but poor regularity due to subtle atrial arrhythmias and cardiac conduction disturbances. Forty-seven per cent of ATTRm amyloidosis patients presented with HRV scores below normal limits, whereas HCM patients presented with higher HRV than ATTRm amyloidosis patients.Conclusions: Reduced HRV is common in ATTRm amyloidosis patients during DB, however, autonomic function cannot be evaluated in patients presenting with the combination of normal scores and low regularity, since their HR responses often reflects dysrhythmias.

  • 142.
    Wixner, Jonas
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Pilebro, Bjorn
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Lundgren, Hans-Erik
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Olsson, Malin
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Anan, Intissar
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Effect of doxycycline and ursodeoxycholic acid on transthyretin amyloidosis2017Ingår i: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 24, nr 1, s. 78-79Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Doxycycline has been shown to disrupt transthyretin amyloid (ATTR) fibrils [1] and tauro-ursodeoxycholic acid (TUDCA) has been shown to reduce TTR toxic aggregates in mice [2]. Further, in 2010 Cardoso et al. showed that a combined doxycycline/TUDCA treatment had a synergistic effect, decreasing ATTR deposition. Ursodeoxycholic acid (UDCA) is a bile acid used for the treatment of certain cholestatic syndromes with an efficacy similar to that of TUDCA. Based on this knowledge, we wanted to explore if treatment with doxycycline and UDCA (Dox/Urso) would prevent disease progression in ATTR amyloidosis. UDCA was selected since TUDCA is not available in Sweden.

  • 143.
    Wixner, Jonas
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Suhr, Ole B.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Anan, Intissar
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Management of gastrointestinal complications in hereditary transthyretin amyloidosis: a single-center experience over 40 years2018Ingår i: Expert Review of Gastroenterology & Hepatology, ISSN 1747-4124, E-ISSN 1747-4132, Vol. 12, nr 1, s. 73-81Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Introduction: Hereditary transthyretin amyloidosis (ATTRm amyloidosis) is a rare disease caused by the deposition and accumulation of insoluble non-native transthyretin fibrils in the body. The disease inevitably results in widespread organ disruption, and poor life expectancy. The GI tract is one organ system vulnerable to disruption and, although the clinical presentation of the disease varies, GI involvement affects most patients with ATTRm amyloidosis.

    Areas covered: This article presents our experience with diagnosing and treating the GI symptoms of ATTRm amyloidosis patients at our center over the last 40 years, in the Swedish clustering area of the disease. Our aim is to help other physicians to better manage GI complications in patients with this rare but widespread condition.

    Expert commentary: GI symptoms are debilitating complications for ATTRm amyloidosis patients to experience, yet with the appropriate questioning and diagnosis methods, symptomatic treatments of these symptoms can be implemented to provide relief. Further, patients with fewer GI complications and a good nutritional status are also better candidates for liver transplantation which, in selected cases, is the best disease-modifying treatment of ATTRm amyloidosis to date.

  • 144.
    Wixner, Jonas
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Törnblom, H.
    Karling, Pontus
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Anan, Intissar
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Lindberg, G.
    Abnormal small bowel motility in patients with hereditary transthyretin amyloidosis2018Ingår i: Neurogastroenterology and Motility, ISSN 1350-1925, E-ISSN 1365-2982, Vol. 30, nr 9, artikel-id e13354Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Gastrointestinal complications are common in hereditary transthyretin amyloid (ATTRm) amyloidosis. The underlying mechanisms have not been fully elucidated, and the patients' small bowel function remains largely unexplored. The aim of the present study was to compare the small bowel motility in ATTRm amyloidosis patients with that in non-amyloidosis patient controls.

    Methods: ATTRm amyloidosis patients undergoing evaluation for liver transplantation were consecutively investigated with 24-hour duodenojejunal manometry (n=19). The somatostatin analogue octreotide was used to induce fasting motility. Patients with age at onset of 50years were defined as late-onset cases. For each patient, three age- and sex-matched patient controls (n=57) were selected from the total pool of investigated patients.

    Key Results: Manometry was judged as abnormal in 58% of the patients and in 26% of the patient controls (P=.01). Patients displayed significantly more daytime phase III migrating motor complexes than patient controls (median 4 vs 2, P<.01), and had a higher frequency of low-amplitude complexes (16% vs 4%; however, this difference did not reach statistical significance, P=.10). Furthermore, late-onset patients showed a delay in octreotide response (5.4 vs 3.8minutes, P<.01), but this was not observed for early-onset patients or within the control group.

    Conclusions and Inferences: Patients with ATTRm amyloidosis displayed abnormalities in their small bowel motility more frequently than non-amyloidosis patient controls, and the manometric pattern was probably best consistent with a combined neuromyopathic disorder. The delayed octreotide response in late-onset patients warrants further investigation.

  • 145. Zou, Ding
    et al.
    Wennman, Heini
    Ekblom, Örjan
    Grote, Ludger
    Arvidsson, Daniel
    Blomberg, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Torén, Kjell
    Bergström, Göran
    Börjesson, Mats
    Hedner, Jan
    Insomnia and cardiorespiratory fitness in a middle-aged population: the SCAPIS pilot study2019Ingår i: Sleep and Breathing, ISSN 1520-9512, E-ISSN 1522-1709, Vol. 23, nr 1, s. 319-326Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BackgroundThe relationship between insomnia and cardiorespiratory fitness (CRF), a well-established risk factor for cardiovascular disease, has not been extensively studied. We aimed to assess the independent association between insomnia and CRF in a population-based cohort of subjects aged 50 to 64years.MethodsSubjects participating in the Swedish CArdioPulmonary bioImaging Study (SCAPIS) pilot cohort (n=603, men 47.9%) underwent a submaximal cycle ergometer test for estimation of maximal oxygen consumption (VO(2)max). Data on physical activity and sedentary time were collected via waist-worn accelerometers. An insomnia severity index score 10 was used to define insomnia.ResultsInsomnia was identified in 31.8% of the population. The VO(2)max was significantly lower in insomnia subjects compared with the non-insomnia group (31.26.3 vs. 32.4 +/- 6.5ml*kg(-1)*min(-1), p=0.028). There was no difference in objectively assessed physical activity or time spent sedentary between the groups. In a multivariate generalized linear model adjusting for confounders, an independent association between insomnia status and lower VO(2)max was found in men, but not in women (=-1.15 [95% CI -2.23--0.06] and -0.09 [-1.09-0.92], p=0.038 and 0.866, respectively).Conclusionsp id=ParWe found a modest, but significant, association between insomnia and lower CRF in middle-aged men, but not in women. Our results suggest that insomnia may link to cardiovascular disease via reduced CRF. Insomnia may require a specific focus in the context of health campaigns addressing CRF.

  • 146. Zovko, Ana
    et al.
    Yektaei-Karin, Elham
    Salamon, Daniel
    Nilsson, Anders
    Wallvik, Jonas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Stenke, Leif
    Montelukast, a cysteinyl leukotriene receptor antagonist, inhibits the growth of chronic myeloid leukemia cells through apoptosis2018Ingår i: Oncology Reports, ISSN 1021-335X, E-ISSN 1791-2431, Vol. 40, nr 2, s. 902-908Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The clinical outcome for patients with chronic myeloid leukemia (CML) has improved significantly with the introduction of tyrosine kinase inhibitors (TKIs). However, their curative potential appears limited, probably as a consequence of TKI-resistant leukemic stem cells (LSCs) that persist as a result of aberrant pathways independent of the well-established oncoprotein Bcr-Abl. One such pathway involves signaling through leukotrienes (LTs), bioactive compounds that have been suggested to play a role in several other malignancies. Cysteinyl LT1 receptor (CysLT1R) has been reported to be overexpressed in a number of solid cancers, and blocking of this receptor with the antagonist montelukast (treatment approved for bronchial asthma) has resulted in the killing of cancer cells. We recently demonstrated that montelukast, alone or in combination with imatinib, can effectively reduce the growth of CML cells, while normal bone marrow cells were left unaffected. Herein, we further investigated the importance of CysLT1R for the survival of CML cells and the mechanisms by which montelukast induces cell death. Knockdown of the CysLT1R of K562 cells with siRNA reduced their growth by 25%. Montelukast had no effect on these cells, while it killed more than 50% of CysLT1R-expressing cells. Growth inhibition exerted by imatinib was unaffected by CysLT1R status. Montelukast-induced killing of K562/JURL-MK1 CML cells was paralleled by Bax overexpression, cytochrome c release, PARP-1 cleavage, and caspase-3 activation, an event further increased in a setting where montelukast was added to imatinib. Wnt/-catenin signaling was activated by CysLT1R and we observed that montelukast could induce proteins in this pathway, a finding of relevance for LSC survival. Thus, montelukast, employed at in vivo-like concentrations, induces the killing of CML cells through apoptotic pathways and may provide an additional, novel therapeutic possibility in CML.

  • 147. Årestedt, Kristofer
    et al.
    Alvariza, Anette
    Boman, Kurt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin. Research Unit, Medicine-Geriatric, Skellefteå, Sweden.
    Öhlén, Joakim
    Goliath, Ida
    Håkanson, Cecilia
    Fürst, Carl Johan
    Brännström, Margareta
    Umeå universitet, Medicinska fakulteten, Institutionen för omvårdnad.
    Symptom Relief and Palliative Care during the Last Week of Life among Patients with Heart Failure: a National Register Study2018Ingår i: Journal of Palliative Medicine, ISSN 1096-6218, E-ISSN 1557-7740, Vol. 21, nr 3, s. 361-367Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Heart failure is a disease with high morbidity, mortality, and physical and psychological burden. More knowledge about the care provided for patients with heart failure close to death is needed.

    Objective: The aim was to describe key aspects of palliative care during the last week of life in patients with heart failure, as reported by healthcare professionals.

    Design: This is a national register study.

    Setting/Subjects: The study included 3981 patients with diagnosed heart failure as the underlying cause of death.

    Measurements: Data were obtained from the Swedish Register of Palliative Care, a national quality register that focuses on patients’ last week of life, independent of diagnosis or care setting. The register includes information about care interventions connected with key aspects of palliative care. Data are reported retrospectively by a nurse or physician at the healthcare unit where the patient dies.

    Results: Only 4.2% of patients with heart failure received specialized palliative care. In their last week of life, symptom prevalence was high, validated scales were seldom used, and symptoms were unsatisfactorily relieved. Around one-fifth (17%) of the patients in the study died alone. Less than half of family members had been offered bereavement support (45%). Moreover, one-third (28%) of the patients and more than half (61%) of the family members were reported to have had end-of-life discussions with a physician during the illness trajectory.

    Conclusion: The results indicate inadequate palliative care for patients with heart failure during their last week of life.

  • 148.
    Ögren, Joachim
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Irewall, Anna-Lotta
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Söderström, Lars
    Mooe, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Long-term, telephone-based follow-up after stroke and TIA improves risk factors: 36-month results from the randomized controlled NAILED stroke risk factor trial2018Ingår i: BMC Neurology, ISSN 1471-2377, E-ISSN 1471-2377, Vol. 18, artikel-id 153Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Strategies are needed to improve adherence to the blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C) level recommendations after stroke and transient ischemic attack (TIA). We investigated whether nurse-led, telephone-based follow-up that included medication titration was more efficient than usual care in improving BP and LDL-C levels 36 months after discharge following stroke or TIA.

    Methods: All patients admitted for stroke or TIA at Ostersund hospital that could participate in the telephone-based follow-up were considered eligible. Participants were randomized to either nurse-led, telephone-based follow-up (intervention) or usual care (control). BP and LDL-C were measured one month after discharge and yearly thereafter. Intervention group patients who did not meet the target values received additional follow-up, including lifestyle counselling and medication titration, to reach their treatment goals (BP < 140/90 mmHg, LDL-C < 2.5 mmol/L). The primary outcome was the systolic BP level 36 months after discharge.

    Results: Out of 871 randomized patients, 660 completed the 36-month follow-up. The mean systolic and diastolic BP values in the intervention group were 128.1 mmHg (95% CI 125.8-1305) and 75.3 mmHg (95% CI 73.8-76.9), respectively. This was 6.1 mmHg (95% CI 3.6-8.6, p < 0.001) and 3.4 mmHg (95% CI 1.8-5.1, p < 0.001) lower than in the control group. The mean LDL-C level was 22 mmol/L in the intervention group, which was 03 mmol/L (95% CI 0.2-0.5, p < 0.001) lower than in controls. A larger proportion of the intervention group reached the treatment goal for BP (systolic: 79.4% vs. 55.3%, p < 0.001; diastolic 90.3% vs. 77.9%, p < 0.001) as well as for LDL-C (69.3% vs. 48.9%, p < 0.001).

    Conclusions: Compared with usual care, a nurse-led telephone-based intervention that included medication titration after stroke or TIA improved BP and LDL-C levels and increased the proportion of patients that reached the treatment target 36 months after discharge.

  • 149.
    Ögren, Joachim
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Irewall, Anna-Lotta
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Söderström, Lars
    Mooe, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Serious hemorrhages after ischemic stroke or TIA - Incidence, mortality, and predictors2018Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, nr 4, artikel-id e0195324Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Data are lacking on the risk and impact of a serious hemorrhage on the prognosis after ischemic stroke (IS) or transient ischemic attack (TIA). We aimed to estimate the incidence of serious hemorrhage, analyze the impact on mortality, and identify predictors of hemorrhage after discharge from IS or TIA.

    Methods and findings: All patients admitted to Östersund Hospital for an IS or TIA in 2010–2013 were included (n = 1528, mean age: 75.1 years). Serious hemorrhages were identified until 31st December 2015. Incidence rates were calculated. The impact on mortality (stratified by functional level) was determined with Kaplan-Meier analysis. Non-parametric estimation under the assumption of competing risk was performed to assess the cumulative incidence and predictors of serious hemorrhages. The incidence rates of serious (n = 113) and intracranial hemorrhages (n = 45) after discharge from IS and TIA were 2.48% and 0.96% per year at risk, respectively. Patients with modified Rankin Scale (mRS) scores of 3–5 exhibited 58.9% mortality during follow-up and those with mRS scores of 0–2 exhibited 18.4% mortality. A serious hemorrhage did not affect mortality in patients with impaired functional status, but it increased the risk of death in patients with mRS scores of 0–2. Hypertension was associated with increased risk of serious hemorrhage.

    Conclusions: We found that, after discharge from an IS or TIA, serious hemorrhages were fairly common. Impairments in function were associated with high mortality, but serious hemorrhages only increased the risk of mortality in patients with no or slight disability. Improved hypertension treatment may decrease the risk of serious hemorrhage, but in patients with low functional status, poor survival makes secondary prevention challenging.

  • 150.
    Öhman, Ludvig
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Johansson, Magdalena
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Jansson, Jan-Håkan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Lind, Marcus
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Johansson, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Positive predictive value and misclassification of diagnosis of pulmonary embolism and deep vein thrombosis in Swedish patient registries2018Ingår i: Clinical Epidemiology, ISSN 1179-1349, E-ISSN 1179-1349, Vol. 10, s. 1215-1221Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose: To validate diagnoses of pulmonary embolism (PE) and deep vein thrombosis (DVT) in administrative registries. We also estimated the frequency of misclassified PE and DVT events.

    Patients and methods: A registry search for ICD codes representing PE and DVT was performed between 1985 and 2014 in a large population-based cohort in northern Sweden. An additional search using an extended set of ICD codes was performed to identify misclassified events. Diagnoses were validated manually by reviewing medical records and radiology reports.

    Results: Searching ICD codes in the National Patient Registry and Cause of Death Registry identified 2,450 participants with a first-time diagnosis of PE or DVT. The positive predictive value (PPV) for a diagnosis of PE or DVT was 80.7% and 59.2%, respectively. For the period of 2009 to 2014, the PPV was higher for PE (85.8%) but lower for DVT (54.1%). Misclassification occurred in 16.4% of DVT events and 1.1% of PE events.

    Conclusion: Registry-based data on PE, especially in recent years, are of acceptable quality and can be considered for use in registry-based studies. For DVT, we found that data were of low quality in regards to both PPV and misclassification and should not be used without validation.

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