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  • 1. Afshin, A
    et al.
    Forouzanfar, M. H
    Reitsma, M. B
    Sur, P
    Estep, K
    Lee, A
    Marczak, L
    Mokdad, A. H
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Uppsala universitet.
    Murray, C. J. L
    Health effects of overweight and obesity in 195 countries over 25 years2017Ingår i: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 377, nr 1, s. 13-27Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Although the rising pandemic of obesity has received major attention in many countries, the effects of this attention on trends and the disease burden of obesity remain uncertain.

    METHODS: We analyzed data from 68.5 million persons to assess the trends in the prevalence of overweight and obesity among children and adults between 1980 and 2015. Using the Global Burden of Disease study data and methods, we also quantified the burden of disease related to high body-mass index (BMI), according to age, sex, cause, and BMI in 195 countries between 1990 and 2015.

    RESULTS: In 2015, a total of 107.7 million children and 603.7 million adults were obese. Since 1980, the prevalence of obesity has doubled in more than 70 countries and has continuously increased in most other countries. Although the prevalence of obesity among children has been lower than that among adults, the rate of increase in childhood obesity in many countries has been greater than the rate of increase in adult obesity. High BMI accounted for 4.0 million deaths globally, nearly 40% of which occurred in persons who were not obese. More than two thirds of deaths related to high BMI were due to cardiovascular disease. The disease burden related to high BMI has increased since 1990; however, the rate of this increase has been attenuated owing to decreases in underlying rates of death from cardiovascular disease.

    CONCLUSIONS: The rapid increase in the prevalence and disease burden of elevated BMI highlights the need for continued focus on surveillance of BMI and identification, implementation, and evaluation of evidence-based interventions to address this problem.

  • 2. Ahlm, Kristin
    et al.
    Lindqvist, Per
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Karolinska institutet.
    Saveman, Britt-Inger
    Björnstig, Ulf
    Suicidal drowning deaths in northern Sweden 1992-2009: The role of mental disorder and intoxication2015Ingår i: Journal of Forensic and Legal Medicine, ISSN 1752-928X, E-ISSN 1878-7487, Vol. 34, s. 168-172Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Suicides by drowning have received limited attention by researchers. A recent finding that almost one-third of all drowning deaths in Sweden were classified as suicide instigated this study. We identified 129 cases of suicide by drowning in Northern Sweden and analyzed the circumstances and the psychiatric history prior to the suicide. Information was obtained from autopsy, police and medical records, as well as from the National Inpatient Register. One-third of the suicide victims had previously attempted suicide and half of the victims had been hospitalized due to mental health problems. One-third of these had left the hospital less than one week before the suicide. Alcohol and psychoactive drugs were present in 16% and 62% of the cases, respectively. A history of mental disorder and previous suicide attempt (s), especially by drowning, is an ominous combination necessitating efficient clinical identification, treatment and follow-up if a complete suicide is to be prevented.

  • 3.
    Andersen, Kasper
    et al.
    Uppsala University, Uppsala, Sweden.
    Lind, Lars
    Uppsala University, Uppsala, Sweden.
    Ingelsson, Erik
    Uppsala University, Uppsala, Sweden.
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Uppsala University, Uppsala, Sweden.
    Byberg, Liisa
    Uppsala University, Uppsala, Sweden.
    Michaëlsson, Karl
    Uppsala University, Uppsala, Sweden.
    Sundström, Johan
    Uppsala University, Uppsala, Sweden.
    Skeletal muscle morphology and risk of cardiovascular disease in elderly men2015Ingår i: European Journal of Preventive Cardiology, ISSN 2047-4873, E-ISSN 2047-4881, Vol. 22, nr 2, s. 231-239Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: While it is well known that physical inactivity is a major risk factor for cardiovascular disease, there is still a search for the mechanisms by which exercise exerts its positive effect. Skeletal muscle fibre type can be affected to some extent by exercise, and different fibre types possess different anti-inflammatory and glucometabolic properties that may influence cardiovascular disease risk.

    DESIGN: Population-based cohort study.

    METHODS: We investigated relations of skeletal muscle morphology to risk of cardiovascular events in a sample of 466 71-year-old men without cardiovascular disease, of which 295 were physically active (strenuous physical activity at least 3 h/week).

    RESULTS: During a median of 13.1 years of follow up, 173 major cardiovascular events occurred. Among physically active men, 10% higher proportion of type-I (slow-twitch oxidative) fibres was associated with a hazard ratio (HR) of 0.84 (95% confidence interval 0.74-0.95) for cardiovascular events, and 10% higher proportion of type-IIx (fast-twitch glycolytic) fibres was associated with a HR of 1.24 (1.06-1.45), adjusting for age. Similar results were observed in several sets of multivariable-adjusted models. No association of muscle fibre type with risk of cardiovascular events was observed among physically inactive men.

    CONCLUSIONS: Higher skeletal muscle proportion of type-I fibres was associated with lower risk of cardiovascular events and a higher proportion of type-IIx fibres was associated with higher risk of cardiovascular events. These relations were only observed in physically active men. Skeletal muscle fibre composition may be a mediator of the protective effects of exercise against cardiovascular disease.

  • 4. Arefalk, Gabriel
    et al.
    Hergens, Maria-Pia
    Ingelsson, Erik
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Michaëlsson, Karl
    Lind, Lars
    Ye, Weimin
    Nyrén, Olof
    Lambe, Mats
    Sundström, Johan
    Smokeless tobacco (snus) and risk of heart failure: results from two Swedish cohorts2010Ingår i: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 28, nr suppl.A, s. E48-E49Artikel i tidskrift (Refereegranskat)
  • 5. Arefalk, Gabriel
    et al.
    Hergens, Maria-Pia
    Ingelsson, Erik
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Michaëlsson, Karl
    Lind, Lars
    Ye, Weimin
    Nyrén, Olof
    Lambe, Mats
    Sundström, Johan
    Smokeless tobacco (snus) and risk of heart failure: results from two Swedish cohorts2012Ingår i: European Journal of Cardiovascular Prevention & Rehabilitation, ISSN 1741-8267, E-ISSN 1741-8275, Vol. 19, nr 5, s. 1120-1127Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Oral moist snuff (snus) is discussed as a safer alternative to smoking, and its use is increasing. Based on its documented effect on blood pressure, we hypothesized that use of snus increases the risk of heart failure.

    Design: Two independent Swedish prospective cohorts; the Uppsala Longitudinal Study of Adult Men (ULSAM), a community-based sample of 1076 elderly men, and the Construction Workers Cohort (CWC), a sample of 118,425 never-smoking male construction workers. Methods: Cox proportional hazards models were used to investigate possible associations of snus use with risk of a first hospitalization for heart failure.

    Results: In ULSAM, 95 men were hospitalized for heart failure, during a median follow up of 8.9 years. In a model adjusted for established risk factors including past and present smoking exposure, current snus use was associated with a higher risk of heart failure [hazard ratio (HR) 2.08, 95% confidence interval (CI) 1.03-4.22] relative to non-use. Snus use was particularly associated with risk of non-ischaemic heart failure (HR 2.55, 95% CI 1.12-5.82). In CWC, 545 men were hospitalized for heart failure, during a median follow up of 18 years. In multivariable-adjusted models, current snus use was moderately associated with a higher risk of heart failure (HR 1.28, 95% CI 1.00-1.64) and non-ischaemic heart failure (HR 1.28, 95% CI 0.97-1.68) relative to never tobacco use.

    Conclusion: Data from two independent cohorts suggest that use of snus may be associated with a higher risk of heart failure.

  • 6. Arking, Dan E
    et al.
    Pulit, Sara L
    Crotti, Lia
    van der Harst, Pim
    Munroe, Patricia B
    Koopmann, Tamara T
    Sotoodehnia, Nona
    Rossin, Elizabeth J
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Uppsala universitet.
    Newton-Cheh, Christopher
    Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization2014Ingår i: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 46, nr 8, s. 826-836Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain similar to 8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD.

  • 7. Arkkukangas, Marina
    et al.
    Johnson, Susanna Tuvemo
    Hellström, Karin
    Anens, Elisabeth
    Tonkonogi, Michail
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Larsson, Ulf
    Fall prevention exercises with or without behavior change support for community-dwelling older adults: a two-year follow-up of a randomized controlled trial2019Ingår i: Journal of Aging and Physical Activity, ISSN 1063-8652, E-ISSN 1543-267X, s. 1-26Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    This study investigates the effectiveness of two fall prevention exercise interventions targeting physical performance, activity level, fall-related self-efficacy, health-related quality of life, and falls: the Otago Exercise Programme (OEP) with and the OEP without behavior change support. In this randomized controlled trial (RCT), 175 participants were randomised into two intervention groups and one control group. A total of 124 community-dwelling older adults over the age of 75 who needed walking aids or home support participated in the two-year follow-up. The OEP with and the OEP without support for behavior change displayed no long-term benefits on physical performance, fall-related self-efficacy, health-related quality of life, and falls compared to a control group. Although no significant differences were detected between the groups, the results implied the control group's physical activity level decreased compared to the intervention groups at two-year follow up.

  • 8.
    Axelsson, Johanna
    et al.
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Tellström, Linda
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Mobil hälsa (m-hälsa) genom användning av mobiltelefon som intervention för barn med övervikt eller fetma.: En systematisk litteraturstudie.2018Självständigt arbete på avancerad nivå (magisterexamen), 10 poäng / 15 hpStudentuppsats (Examensarbete)
    Abstract [sv]

    Bakgrund:

    Förekomsten av övervikt och fetma bland barn ökar i stora delar av världen.

    Brist på fysisk aktivitet är en av orsakerna bakom övervikt och fetma. För barn med

    fetma kan små mängder fysisk aktivitet ha stora positiva hälsoeffekter. Det finns ett

    behov av att utveckla nya effektiva strategier för att öka mängden fysisk aktivitet bland

    barn med övervikt eller fetma. Mobil hälsa (m-hälsa) används som ett paraplybegrepp

    för hälsotjänster förmedlade genom mobila enheter och definieras som ”medicinsk eller

    offentlig hälsoutövning som stöds av mobila enheter så som mobiltelefoner, anordningar

    för patientövervakning, personliga digitala assistenter och andra trådlösa enheter”. En

    potentiell strategi för att påverka mängden fysisk aktivitet bland barn med övervikt eller

    fetma är m-hälsa genom användning av mobiltelefon.

    Syfte:

    Att kartlägga och beskriva vilka interventioner med m-hälsokomponent genom

    användning av mobiltelefon som utvärderat fysisk aktivitet eller Body Mass Index

    (BMI) bland barn med övervikt eller fetma.

    Metod:

    En systematisk litteraturstudie där studier som beskrev interventioner med mhälsokomponenter

    för målgruppen barn 0-18 år med övervikt eller fetma inkluderades.

    Sökning genomfördes i tre vetenskapliga databaser.

    Resultat:

    Sökningarna resulterade i 649 studier av vilka 16 mötte uppsatta

    inklusionskriterier. M-hälsokomponenten innefattade i de flesta studier användning av

    sms och i några studier användning av app. Funktionen med m-hälsokomponenten

    studerades och delades in i självregistrering, kommunikation, uppmuntran, utbildning

    och påminnelse. De inkluderade studierna rapporterade olika former av BMI där två

    studier visade på signifikanta skillnader mellan interventions-och kontrollgrupp med

    störst minskning för interventionsgruppen. Få studier rapporterade objektivt mätt tid i

    fysisk aktivitet på måttlig till hög intensitet.

    Slutsats:

    Den vanligast förekommande interventionen med m-hälsokomponent genom

    användning av mobiltelefon bland barn med övervikt eller fetma var sms. För att kunna

    förstå och jämföra på vilket sätt m-hälsa kan användas skulle ett ramverk för beskrivning

    av dessa interventioner underlätta.

  • 9.
    Balaile, Gunnel
    Högskolan Dalarna, Akademin Hälsa och samhälle, Medicinsk vetenskap.
    The Meaning of Health and Sexuality as experienced by Tanzanian Men and Women living with HIV/AIDS2007Licentiatavhandling, monografi (Övrigt vetenskapligt)
    Abstract [en]

    Background: Sub-Saharan Africa has for more than two decades been hit by Human immunodeficiency virus/ Acquired immune-deficiency Syndrome, HIV/AIDS pandemic with a few signs of decline. In Tanzania, the prevalence of HIV is estimated to 7 percent and about 1.8 million Tanzanians are living with HIV. Women are the hardest hit and most vulnerable are young women 15-24 years old, who are three times more likely to be infected than young men in the same age group and the prevalence is higher in urban than in rural areas. Aim: The overall aim of this thesis was to explore the meaning of health and sexuality among men and women living with HIV/AIDS. Methods: Two studies were conducted in Tanzania, Dar es Salaam during January and February in year 2004 (I, II). Twenty participants were recruited (10 men and 10 women) by the help from health staff and sampled purposely in order to get an equal variety of age, education, religion, sex, and marital status. The interviews took place at one district hospital, and at two different clinics run by Non Governmental Organizations (NGO) one located in a business area in central town, the other NGO clinic outside town in an industrial area. The interviews were transcribed and translated into English. A phenomenological – hermeneutic approach and in-depth interviews were used to collect data. The text was ana¬lysed following Ricoeur’s interpretation theory for text. Findings: The thesis presents aspects of men’s and women’s experiences of living with HIV/AIDS. Adjustment to living with the virus was different between men and women. Men often conceived a growing suspicion that they might be in¬fected by HIV, while women had to be asked by relatives or had to wait for others to be tested. The overwhelming fear of being tested was related to the fear of being stigmatized. Under¬standing the meaning of health and sexuality when living with HIV/AIDS, was for the men living life with a preserved sense of integrity and self-esteem, this meant not to be seen as victims. To the women, however, the reality was it meant being cast into poverty and created devastation of intimate relations. Men had learnt to perform safe sex and had chosen to live with one partner/wife giving them an opportunity to develop new aspects of their intimate life. Conversely, the women felt miserable and had not accepted their diagnosis in the same way. They lacked resources to maintain health and the ability to support their children. The women who lived in a single household had abandoned sex life, their worries and deep concerns were for their children who brought meaning and joy in their lives. Conclusion: For both men and women the meaning of health and sexuality had changed after knowing their sero-status. The men had accepted to live with an altered health and treated symptoms early. The were able to handle feelings, they felt optimistic and strived to live a normal life as possible health had for the women lost meaning in that sense it was not possible to maintain. The men viewed their sex life still important, and tried to be able live a normal life. The women had accepted a life there sexuality had no place. To prevent further HIV infection meant to be educated and fully understand how to prevent the spread of HIV, to act in a responsible way, to be faithful, and/or to accept abstinence. This new way of living meant to be a caring man or woman. The use of condoms had not been completely accepted as the knowledge on how to use the condoms properly was not entirely accomplished. Support from counselors and peers were proved invaluable adjust to a life of living with HIV/AIDS.

  • 10.
    Balaile, Gunnel
    et al.
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Laisser, Rose
    Ransjö-Arvidson, Anna-Berit
    Höjer, Bengt
    Poverty and devastation of intimate relations: Tanzanian women's experience of living with HIV/AIDS2007Ingår i: Journal of the Association of Nurses in AIDS Care, ISSN 1055-3290, E-ISSN 1552-6917, Vol. 18, nr 5, s. 6-16Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In Tanzania, women of reproductive age constitute the largest group infected by HIV. This study aimed to explore the lived experiences related to health and sexuality of Tanzanian women who had known their positive serostatus for I year. In-depth interviews with 10 women were analyzed using a phenomeno-logical-hermeneutic approach and showed frustration and despair at not having resources to maintain daily life. The women needed regular medical treatment for themselves and for their HIV-positive children. Their sexual desires had declined or vanished, and they had come to view sexuality as a source of transmittable disease. For some women, casual sex was an option to solve urgent financial needs. Happiness was something for their children, not for them. Access to social support from the women's community would help prevent further HIV transmission and enhance survival so the children could grow up with at least one devoted parent.

  • 11. Bandak, Ghassan
    et al.
    Sang, Yingying
    Gasparini, Alessandro
    Chang, Alex R
    Ballew, Shoshana H
    Evans, Marie
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Uppsala universitet.
    Lund, Lars H
    Inker, Lesley A
    Grams, Morgan E
    Hyperkalemia after initiating renin-angiotensin system blockade: The Stockholm creatinine measurements (SCREAM) project2017Ingår i: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 6, nr 7, artikel-id e005428Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Concerns about hyperkalemia limit the use of angiotensin-converting enzyme inhibitors (ACE-I) and angiotensin receptor blockers (ARBs), but guidelines conflict regarding potassium-monitoring protocols. We quantified hyperkalemia monitoring and risks after ACE-I/ARB initiation and developed and validated a hyperkalemia susceptibility score.

    METHODS AND RESULTS: We evaluated 69 426 new users of ACE-I/ARB therapy in the Stockholm Creatinine Measurements (SCREAM) project with medication initiation from January 1, 2007 to December 31, 2010, and follow-up for 1 year thereafter. Three fourths (76%) of SCREAM patients had potassium checked within the first year. Potassium >5 and >5.5 mmol/L occurred in 5.6% and 1.7%, respectively. As a comparison, we propensity-matched new ACE-I/ARB users to 20 186 new β-blocker users in SCREAM: 64% had potassium checked. The occurrence of elevated potassium levels was similar between new β-blocker and ACE-I/ARB users without kidney disease; only at estimated glomerular filtration rate <60 mL/min per 1.73 m(2) were risks higher among ACE-I/ARB users. We developed a hyperkalemia susceptibility score that incorporated estimated glomerular filtration rate, baseline potassium level, sex, diabetes mellitus, heart failure, and the concomitant use of potassium-sparing diuretics in new ACE-I/ARB users; this score accurately predicted 1-year hyperkalemia risk in the SCREAM cohort (area under the curve, 0.845, 95% CI: 0.840-0.869) and in a validation cohort from the US-based Geisinger Health System (N=19 524; area under the curve, 0.818, 95% CI: 0.794-0.841), with good calibration.

    CONCLUSIONS: Hyperkalemia within the first year of ACE-I/ARB therapy was relatively uncommon among people with estimated glomerular filtration rate >60 mL/min per 1.73 m(2), but rates were much higher with lower estimated glomerular filtration rate. Use of the hyperkalemia susceptibility score may help guide laboratory monitoring and prescribing strategies.

  • 12. Barber, Ryan M
    et al.
    Fullman, Nancy
    Sorensen, Reed J
    Bollyky, Thomas
    McKee, Martin
    Nolte, Ellen
    Abajobir, Amanuel Alemu
    Abete, Kalkidan Hassen
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Karolinska institutet.
    Murray, Christopher J L
    Healthcare Access and Quality Index based on mortality from causes amenable to personal health care in 195 countries and territories, 1990–2015: a novel analysis from the Global Burden of Disease Study 20152017Ingår i: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 390, nr 10091, s. 231-266Artikel i tidskrift (Refereegranskat)
  • 13. Basu, S
    et al.
    Zethelius, B
    Helmersson, J
    Berne, C
    Larsson, A
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Cytokine-mediated inflammation is independently associated with insulin sensitivity measured by the euglycemic insulin clamp in a community-based cohort of elderly men2011Ingår i: International Journal of Clinical and Experimental Medicine, ISSN 1940-5901, E-ISSN 1940-5901, Vol. 4, nr 2, s. 164-168Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Both clinical and experimental studies suggest a close relation between an inflammatory state and insulin resistance. We investigated the association between cytokine-mediated inflammation (high sensitivity C reactive protein [hsCRP] and interleukin [IL] 6) and insulin sensitivity (insulin-mediated glucose disposal rate, assessed by the euglycemic insulin clamp) in a community-based cohort, with subgroup analyses of normal weight individuals without diabetes mellitus and metabolic syndrome (NCEP). hsCRP and IL- 6 were inversely associated with insulin sensitivity (multivariable-adjusted regression coefficient for 1-SD increase of hsCRP -0.12 (-0.21-(-0.03), p=0.01) and of IL-6 - 0.11 (-0.21-(-0.02), p=0.01) in models adjusting for age and components of the metabolic syndrome (systolic and diastolic blood pressure, antihypertensive drugs, HDL-cholesterol, triglycerides, fasting plasma glucose, waist circumference). The multivariable-adjusted association between hsCRP, IL-6 and insulin sensitivity were of a similar magnitude in normal weight individuals without diabetes and without the metabolic syndrome. Our data show that cytokine -mediated subclinical inflammation is independently associated with decreased insulin sensitivity also in apparently metabolically healthy normal weight individuals, indicating that the interplay between inflammatory processes and insulin resistance is present already in the early stages of the development of glucometabolic disease. (IJCEM1012002).

  • 14. Beijer, K.
    et al.
    Nowak, C.
    Sundström, J.
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Karolinska Institutet.
    Fall, T.
    Lind, L.
    In search of causal pathways in diabetes: a study using proteomics and genotyping data from a cross-sectional study2019Ingår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428Artikel i tidskrift (Refereegranskat)
  • 15.
    Bellardini, Helena
    et al.
    Högskolan Dalarna, Akademin Hälsa och samhälle, Idrotts- och hälsovetenskap.
    Henriksson, Anders
    Högskolan Dalarna, Akademin Hälsa och samhälle, Idrotts- och hälsovetenskap.
    Tonkonogi, Michail
    Högskolan Dalarna, Akademin Hälsa och samhälle, Medicinsk vetenskap.
    Bra och enkla fystester2013Bok (Övrigt vetenskapligt)
  • 16.
    Bellardini, Helena
    et al.
    Högskolan Dalarna, Akademin Hälsa och samhälle, Medicinsk vetenskap.
    Henriksson, Anders
    Högskolan Dalarna, Akademin Hälsa och samhälle, Medicinsk vetenskap.
    Tonkonogi, Michail
    Högskolan Dalarna, Akademin Hälsa och samhälle, Medicinsk vetenskap.
    Tester och mätmetoder för idrott och hälsa2009Bok (Övrigt vetenskapligt)
  • 17.
    Bellardini, Helena
    et al.
    Högskolan Dalarna, Akademin Hälsa och samhälle, Medicinsk vetenskap.
    Knutsson, Magnus
    Högskolan Dalarna, Akademin Hälsa och samhälle, Medicinsk vetenskap.
    Tonkonogi, Michail
    Högskolan Dalarna, Akademin Hälsa och samhälle, Medicinsk vetenskap.
    Inverkan av olika farthållningsstrategier på prestationsförmåga vid kortvarigt maximalt fysiskt arbete.2006Ingår i: Svensk Idrottsforskning: Organ för Centrum för Idrottsforskning, ISSN 1103-4629, nr 2, s. 20-26Artikel i tidskrift (Övrigt vetenskapligt)
  • 18.
    Bellardini, Helena
    et al.
    Högskolan Dalarna, Akademin Hälsa och samhälle, Idrotts- och hälsovetenskap.
    Tonkonogi, Michail
    Högskolan Dalarna, Akademin Hälsa och samhälle, Medicinsk vetenskap.
    Senior Power - Styrketräning för äldre2013 (uppl. 1)Bok (Övrigt vetenskapligt)
  • 19.
    Bengtsson, Anette
    et al.
    Högskolan Dalarna, Akademin Hälsa och samhälle, Medicinsk vetenskap.
    Lyckström, Marie
    Högskolan Dalarna, Akademin Hälsa och samhälle, Medicinsk vetenskap.
    Anhörigvårdarnas upplevelser i hemmet vid livets slutskede, med hjälp av palliativa teamet2008Självständigt arbete på grundnivå (kandidatexamen)Studentuppsats (Examensarbete)
    Abstract [sv]

    Idag ökar den palliativa omvårdnaden i hemmet. För att den sjuke ofta har en önskan om att få dö hemma. Det ställer krav på anhörigvårdarna som är dem som kommer att bli dem primära vårdarna. Syftet med studien var att undersöka anhörigvårdarnas upplevelser av att vårda hemma, i livets slutskede, med hjälp av det palliativa teamet. Studien genomfördes som en systematisk litteraturstudie. Genom litteraturstudien fick man fram de positiva och negativa upplevelserna från anhörigvårdarna som vårdat den sjuke i hemmet. Studien visade att anhörigvårdarna skulle välja att vårda den sjuke i hemmet igen med hjälp av det palliativa teamet. Detta trots att flera negativa upplevelser kom fram. Anhörigvårdarna ville vara mer delaktiga i omvårdnadsarbetet och detta gjorde att anhörigvårdarna upplevde en större tillfredställelse av själv, genom att kunna ge något tillbaka till den sjuke. Anhörigvårdarna önskade mer stöd från vårdpersonalen eftersom de ansåg sig ha bristande kompetens om medicinteknik, kroppens hälsa, sjukdomen, dess symptom, behandling, och prognos etc.

  • 20.
    Bergman Bruhn, Åsa
    et al.
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Olai, Lena
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Omvårdnad.
    Utvärdering av Hemsjukvården i Dalarna 2014: Slutrapport2019Rapport (Övrigt vetenskapligt)
  • 21.
    Bergqvist, Yngve
    et al.
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Bergquist, Jonas
    In memory of Niklas Lindegardh2012Ingår i: Bioanalysis, ISSN 1757-6180, E-ISSN 1757-6199, Vol. 4, nr 6, s. 751-751Artikel i tidskrift (Refereegranskat)
  • 22. Bergström, Aileen L
    et al.
    Guidetti, Susanne
    Tistad, Malin
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Tham, Kerstin
    von Koch, Lena
    Eriksson, Gunilla
    Perceived occupational gaps one year after stroke: An explorative study2011Ingår i: Journal of Rehabilitation Medicine, ISSN 1651-2081, Vol. 44, nr 1, s. 36-42Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: To explore and describe factors associated with occupational gaps and to identify factors at 3 months that predict occupational gaps one year post-stroke. A gap, a restriction in participation, is considered to be present when there is a discrepancy between what the individual wants to do and what they actually do in everyday life. DESIGN: Prospective longitudinal study. SUBJECTS: Two hundred persons with stroke. METHODS: Data from the Occupational Gaps Questionnaire, one year post-stroke, was used as the dependent variable in 3- and 12-month regression analyses. Domains of the Stroke Impact Scale, global life satisfaction, demographic and medical factors were used as independent variables. RESULTS: At 3 months, activities of daily living abilities, social participation and not being born in Sweden predicted occupational gaps at 12 months. Stroke severity and not being born in Sweden and 3 factors at 12 months: social participation, self-rated recovery, and global life satisfaction were associated with occupational gaps. CONCLUSION: Activities of daily living ability at 3 months predicted occupational gaps after stroke. Thus, it is possible to identify early on, and provide interventions for, those that risk participation restrictions. Not being born in the country might be an indicator of a risk for participation restrictions.

  • 23.
    Berterud Andersson, Catarina
    et al.
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Dennis, Katarina
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Lumbal spinal stenos och fotbäddar: Kan av formgjutna fotbäddar minska kvarstående ländrygg- och bensmärta hos patienter som opererats för lumbal spinal stenos? En kvasi-experimentell jämförande studie.2018Självständigt arbete på avancerad nivå (magisterexamen), 10 poäng / 15 hpStudentuppsats (Examensarbete)
    Abstract [sv]

    Bakgrund: Lumbal spinal stenos (LSS) är ett vanligt förekommande patologiskt tillstånd i ländryggen. Det vanligaste målet för interventioner vid behandling av LSS är minskad smärta i rygg och ben. Kunskapsläget gällande fotbäddar vid ländryggssmärta är bristfälligt. Syfte: Syftet med denna studie var att undersöka om individuellt utformade fotbäddar minskar självskattad smärtintensitet i rygg och i ben bland patienter med kvarstående smärta efter operation för LSS. Syftet var också att jämföra interventionsgruppens självskattade smärtintensitet i rygg och ben samt ryggrelaterade funktion efter interventionen med hur en kontrollgrupp, som genomgått samma operation två år tidigare, skattade vid sin ettårs-uppföljning. Metod: Elva personer som opererats för LSS på Ryggkirurgiska kliniken i Strängnäs fick individuellt utformade fotbäddar i sex veckor. Bakgrundskaraktäristika var kön, ålder, självskattad smärta i rygg och ben samt självskattad ryggrelaterad funktion. Primära utfallsmått var smärtintensitet i rygg och ben, utvärderat med Numeric Rating Scale (NRS). Sekundärt utfallsmått var ryggrelaterad funktion mätt med Oswestry Low Back Pain Disability Index (ODI). Förändring av interventionsgruppens medianvärde för smärtintensitet före jämfört med efter intervention beräknades med Wilcoxon signed rank sum test (CI 95%). Uppföljningsvärdet på variablerna jämfördes med motsvarande värden från en kontrollgrupp vars data kom från Svenska ryggregistret, Swespine. Resultat: Det var ingen skillnad i självskattad smärtintensitet för rygg före och efter interventionen (p=0,76). Det var inte heller någon skillnad i självskattad smärtintensitet för ben före och efter intervention (p=0,40). Ingen skillnad sågs mellan interventionsgruppens uppföljningsvärde och kontrollgruppens skattningar vid ettårskontroll avseende smärta i rygg (p=0,078) eller ben (p=0,85). Slutsats: Resultatet i denna studie visade ingen skillnad i självskattad smärtintensitet avseende rygg- eller bensmärta hos interventionsgruppen efter sex veckors användning av fotbäddar. Det var ingen skillnad för självskattad smärtintensitet för rygg- eller bensmärta mellan interventionsgrupp och kontrollgrupp.

  • 24.
    Blessborn, Daniel
    et al.
    Högskolan Dalarna, Akademin Industri och samhälle, Kemiteknik.
    Römsing, Susanne
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Kemi.
    Bergqvist, Yngve
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Lindegardh, Niklas
    Assay for screening for six antimalarial drugs and one metabolite using dried blood spot sampling, sequential extraction and ion-trap detection2010Ingår i: Bioanalysis, ISSN 1757-6180, E-ISSN 1757-6199, Vol. 2, nr 11, s. 1839-1847Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: More parasites are becoming resistant to antimalarial drugs, and in many areas a change in first-line drug treatment is necessary. The aim of the developed assay is to help determine drug use in these areas and also to be a complement to interviewing patients, which will increase reliability of surveys.

    Results: This assay detects quinine, mefloquine, sulfadoxine, pyrimethamine, lumefantrine, chloroquine and its metabolite desethylchloroquine in a 100-mu l dried blood spot. Most of the drugs also have long half-lives that make them detectable at least 7 days after administration. The drugs are extracted from the dried blood spot with sequential extraction (due to the big differences in physicochemical properties), solid-phase extraction is used as sample clean-up and separation is performed with gradient-LC with MS ion-trap detection.

    Conclusion: Detection limits (S/N > 5:1) at 50 ng/ml or better were achieved for all drugs except lumefantrine (200 ng/ml), and thus can be used to determine patient compliance. A major advantage of using the ion-trap MS it that it will be possible to go back into the data and look for other drugs as needed.

  • 25. Blomberg, Jonas
    et al.
    Blomberg, Fredrik
    Sjösten, Anna
    Sheikholvaezin, Ali
    Bolin-Wiener, Agnes
    Elfaitouri, Amal
    Hessel, Sanna
    Gottfries, Carl-Gerhard
    Zachrisson, Olof
    Ohrmalm, Christina
    Jobs, Magnus
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Pipkorn, Ruediger
    No evidence for xenotropic murine leukemia-related virus infection in Sweden using internally controlled multiepitope suspension array serology2012Ingår i: Clinical and Vaccine Immunology, ISSN 1556-6811, E-ISSN 1556-679X, Vol. 19, nr 9, s. 1399-1410Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Many syndromes have a large number of differential diagnoses, a situation which calls for multiplex diagnostic systems. Myalgic encephalomyelitis (ME), also named chronic fatigue syndrome (CFS), is a common disease of unknown etiology. A mouse retrovirus, xenotropic murine leukemia-related virus (XMRV), was found in ME/CFS patients and blood donors, but this was not corroborated. However, the paucity of serological investigations on XMRV in humans prompted us to develop a serological assay which cover many aspects of XMRV antigenicity. It is a novel suspension array method, using a multiplex IgG assay with nine recombinant proteins from the env and gag genes of XMRV and 38 peptides based on known epitopes of vertebrate gamma-retroviruses. IgG antibodies were sought in 520 blood donors and 85 ME/CFS patients and in positive-and negative-control sera from animals. We found no differences in seroreactivity between blood donors and ME/CFS patients for any of the antigens. This did not support an association between ME/CFS and XMRV infection. The multiplex serological system had several advantages: (i) biotinylated protein G allowed us to run both human and animal sera, which is essential because of a lack of XMRV-positive humans; (ii) a novel quality control was a pan-peptide positive-control rabbit serum; and (iii) synthetic XMRV Gag peptides with degenerate positions covering most of the variation of murine leukemia-like viruses did not give higher background than nondegenerate analogs. The principle may be used for creation of variant tolerant peptide serologies. Thus, our system allows rational large-scale serological assays with built-in quality control.

  • 26.
    Borg, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Commentary on selection of assistive technology in a context with limited resources2019Ingår i: Disability and Rehabilitation: Assistive Technology, ISSN 1748-3107, E-ISSN 1748-3115Artikel i tidskrift (Refereegranskat)
  • 27. Bozkurt Ahman, H
    et al.
    Giedraitis, V
    Cedervall, Y
    Berglund, L
    McKee, Kevin
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Socialt arbete.
    Rosendahl, E
    Ingelsson, M
    Åberg, Anna Cristina
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Correlations Between Dual-Task Performance and Alzheimer’s Disease Cerebrospinal Fluid Biomarkers2018Konferensbidrag (Refereegranskat)
  • 28. Bozkurt Åhman, H
    et al.
    Cedervall, Y
    Giedraitis, V
    Berglund, L
    McKee, Kevin
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Socialt arbete.
    Rosendahl, E
    Ingelsson, M
    Åberg, Anna Cristina
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Combining Two Dual-Task Tests to Discriminate Between People with Dementia Disorder, Mild Cognitive Impairment, Subjective Cognitive Impairment, and Healthy Controls2019Konferensbidrag (Refereegranskat)
  • 29. Bozkurt Åhman, H
    et al.
    Giedraitis, V
    Cedervall, Y
    Berglund, L
    McKee, Kevin
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Socialt arbete.
    Rosendahl, E
    Ingelsson, M
    Åberg, Anna Cristina
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Correlations Between Dual-Task Performance and Alzheimer’s Disease Cerebrospinal Fluid Biomarkers2019Konferensbidrag (Refereegranskat)
  • 30.
    Brorsson, Sofia
    et al.
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Idrotts- och hälsovetenskap.
    Carlsson, Tomas
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Carlsson, Magnus
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    A new electronic grip force measurement device for hand evaluation2013Ingår i: Abstracts of the Annual European Congress of Rheumatology EULAR. June 12-15, 2013. Madrid, Spain, 2013Konferensbidrag (Refereegranskat)
    Abstract [en]

    Background: Hand grip force is a good indicator of general muscle strength and can also be used to predict multiple outcomes such as changes in activities of daily living (ADL), disability, mortality and general upper extremity strength. Hand grip force is often measured as the amount of static grip force a subject can produce when measured with a hydraulic dynamometer such as the Jamar or with an electronic device such as the Grippit. The Grippit device measures an average grip force, a peak grip force and force over a set time period. Grippit has shown good reliability for healthy subjects. Grippit, which was developed over 20 years ago in Gothenburg, Sweden is no longer manufactured. Therefore, the need for anewly developed and modernized measurement instrument for use in evaluating hand rehabilitation has arisen.

    Objectives: The aim of this study was to evaluate the test-retest reliability of the newly developed instrument GRIP-it and to describe and validate the relationship between grip force measurements from GRIP-it and the original Grippit device.

    Methods: Healthy controls (n=43) were included in the study. Two devices were used to evaluate grip force (Newton, N), (i) GRIP-it a newly developed device and (ii) Grippit. Both instruments were used to measure mean and maximal force over 10 seconds.

    Results: GRIP-it displayed a mean measurement error of -1.7 ± 0.5% and the corresponding error for Grippit was -1.6 ± 1.9%. All subjects completed the grip force tests and the results for three attempts for each hand. The test-retest reliability was excellent for both pieces of equipment, with ICCs ranging from 0.963 to 0.947 (CI 95% between 0.103 and 0.041) for GRIP-it and from 0.979 to 0.968 (CI 95% between 0.087 and 0.042) for Grippit.

    Relationships between Grippit and GRIP-it

    There was a significant difference between the measured values derived from Grippit and GRIP-it for both the dominant hand (P < 0.001) and the non-dominant hand (P < 0.01). Grippit gives in general a higher grip force measurement than GRIP-it which is also indicated by the slope (β1) of the regression lines that deviates from 1. However, there were no substantial differences in the grip force when comparing the measurements for the dominant hand with the non-dominant hand for either Grippit (P = 0.071) or GRIP-it (P = 0.404). Based on these non-significant differences between hands and the fact that the model estimates for the intercept (β0) and the slope (β1) are contained within the confidence intervals of the model estimates for the opposite hand, a combined model was derived. The linear regression analysis, with grip force measurements for both hands included, gives: GRIP-it = 49.0 + 0.779 · Grippit. This explains 89.6% of the variance in grip force analyzed by GRIP-it (P < 0.001) see Figure 2. To enable an estimation of grip force measured by Grippit based on GRIP-it values a regression analysis with Grippit as dependent variable gives: Grippit = -18.1 + 1.15 · GRIP-it, which explains 89.6% of the variance in grip force analyzed by Grippit (P < 0.001).

    Conclusions: This study showed that GRIP-it has excellent test-retest reliability. Measurements of grip force with GRIP-it are strongly related to those from the original Grippit. The newly developed GRIP-it shows great potential for use in the assessment of hand function and the evaluation of hand rehabilitation.

  • 31. Brück, Katharina
    et al.
    Jager, Kitty J
    Dounousi, Evangelia
    Kainz, Alexander
    Nitsch, Dorothea
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Uppsala university.
    Rothenbacher, Dietrich
    Browne, Gemma
    Capuano, Vincenzo
    Ferraro, Pietro Manuel
    Methodology used in studies reporting chronic kidney disease prevalence: a systematic literature review2015Ingår i: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 30, nr Supp. 4, s. iv6-iv16Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Many publications report the prevalence of chronic kidney disease (CKD) in the general population. Comparisons across studies are hampered as CKD prevalence estimations are influenced by study population characteristics and laboratory methods.

    METHODS: For this systematic review, two researchers independently searched PubMed, MEDLINE and EMBASE to identify all original research articles that were published between 1 January 2003 and 1 November 2014 reporting the prevalence of CKD in the European adult general population. Data on study methodology and reporting of CKD prevalence results were independently extracted by two researchers.

    RESULTS: We identified 82 eligible publications and included 48 publications of individual studies for the data extraction. There was considerable variation in population sample selection. The majority of studies did not report the sampling frame used, and the response ranged from 10 to 87%. With regard to the assessment of kidney function, 67% used a Jaffe assay, whereas 13% used the enzymatic assay for creatinine determination. Isotope dilution mass spectrometry calibration was used in 29%. The CKD-EPI (52%) and MDRD (75%) equations were most often used to estimate glomerular filtration rate (GFR). CKD was defined as estimated GFR (eGFR) <60 mL/min/1.73 m(2) in 92% of studies. Urinary markers of CKD were assessed in 60% of the studies. CKD prevalence was reported by sex and age strata in 54 and 50% of the studies, respectively. In publications with a primary objective of reporting CKD prevalence, 39% reported a 95% confidence interval.

    CONCLUSIONS: The findings from this systematic review showed considerable variation in methods for sampling the general population and assessment of kidney function across studies reporting CKD prevalence. These results are utilized to provide recommendations to help optimize both the design and the reporting of future CKD prevalence studies, which will enhance comparability of study results.

  • 32. Brück, Katharina
    et al.
    Stel, Vianda S
    Gambaro, Giovanni
    Hallan, Stein
    Völzke, Henry
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Uppsala universitet.
    Kastarinen, Mika
    Guessous, Idris
    Vinhas, José
    Stengel, Bénédicte
    CKD prevalence varies across the European general population2016Ingår i: Journal of the American Society of Nephrology, ISSN 1046-6673, E-ISSN 1533-3450, Vol. 27, nr 7, s. 2135-2147Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    CKD prevalence estimation is central to CKD management and prevention planning at the population level. This study estimated CKD prevalence in the European adult general population and investigated international variation in CKD prevalence by age, sex, and presence of diabetes, hypertension, and obesity. We collected data from 19 general-population studies from 13 European countries. CKD stages 1-5 was defined as eGFR<60 ml/min per 1.73 m(2), as calculated by the CKD-Epidemiology Collaboration equation, or albuminuria >30 mg/g, and CKD stages 3-5 was defined as eGFR<60 ml/min per 1.73 m(2). CKD prevalence was age- and sex-standardized to the population of the 27 Member States of the European Union (EU27). We found considerable differences in both CKD stages 1-5 and CKD stages 3-5 prevalence across European study populations. The adjusted CKD stages 1-5 prevalence varied between 3.31% (95% confidence interval [95% CI], 3.30% to 3.33%) in Norway and 17.3% (95% CI, 16.5% to 18.1%) in northeast Germany. The adjusted CKD stages 3-5 prevalence varied between 1.0% (95% CI, 0.7% to 1.3%) in central Italy and 5.9% (95% CI, 5.2% to 6.6%) in northeast Germany. The variation in CKD prevalence stratified by diabetes, hypertension, and obesity status followed the same pattern as the overall prevalence. In conclusion, this large-scale attempt to carefully characterize CKD prevalence in Europe identified substantial variation in CKD prevalence that appears to be due to factors other than the prevalence of diabetes, hypertension, and obesity.

  • 33. Burgaz, A.
    et al.
    Byberg, L.
    Rautiainen, S.
    Orsini, N.
    Hakansson, N.
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Sundstrom, J.
    Lind, L.
    Melhus, H.
    Michaelsson, K.
    Wolk, A.
    Confirmed hypertension and plasma 25(OH)D concentrations amongst elderly men2011Ingår i: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 269, nr 2, s. 211-218Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives. The results of experimental studies suggest that vitamin D deficiency activates the renin-angiotensin system and predisposes to hypertension. Results of previous epidemiological studies investigating the association between 25-hydroxyvitamin D [25(OH)D] status and hypertension have not been consistent, perhaps because of their sole reliance on office blood pressure (BP) measurements leading to some misclassification of hypertension status. No previous studies have examined the association between 25(OH)D status and confirmed hypertension assessed with both office and 24-h BP measurements.

    Design. In this cross-sectional study, we investigated 833 Caucasian men, aged 71 +/- 0.6 years, to determine the association between plasma 25(OH)D concentrations, measured with high-pressure liquid chromatography mass spectrometry, and the prevalence of hypertension. We used both supine office and 24-h BP measurements for classifying participants as normotensive or confirmed hypertensive; participants with inconsistent classifications were excluded.

    Results. In a multivariable adjusted logistic regression model, men with 25(OH)D concentrations < 37.5 nmol L-1 had a 3-fold higher prevalence of confirmed hypertension compared to those with >= 37.5 nmol L-1 25(OH)D (odds ratio = 3.3, 95% CI: 1.0-11.0).

    Conclusions. Our results show that low plasma 25(OH)D concentration is associated with a higher prevalence of confirmed hypertension.

  • 34. Böger, Carsten A
    et al.
    Chen, Ming-Huei
    Tin, Adrienne
    Olden, Matthias
    Köttgen, Anna
    de Boer, Ian H
    Fuchsberger, Christian
    O'Seaghdha, Conall M
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Uppsala universitet.
    Kao, W. H. L
    CUBN is a gene locus for albuminuria2011Ingår i: Journal of the American Society of Nephrology, ISSN 1046-6673, E-ISSN 1533-3450, Vol. 22, nr 3, s. 555-70Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Identification of genetic risk factors for albuminuria may alter strategies for early prevention of CKD progression, particularly among patients with diabetes. Little is known about the influence of common genetic variants on albuminuria in both general and diabetic populations. We performed a meta-analysis of data from 63,153 individuals of European ancestry with genotype information from genome-wide association studies (CKDGen Consortium) and from a large candidate gene study (CARe Consortium) to identify susceptibility loci for the quantitative trait urinary albumin-to-creatinine ratio (UACR) and the clinical diagnosis microalbuminuria. We identified an association between a missense variant (I2984V) in the CUBN gene, which encodes cubilin, and both UACR (P = 1.1 × 10−11) and microalbuminuria (P = 0.001). We observed similar associations among 6981 African Americans in the CARe Consortium. The associations between this variant and both UACR and microalbuminuria were significant in individuals of European ancestry regardless of diabetes status. Finally, this variant associated with a 41% increased risk for the development of persistent microalbuminuria during 20 years of follow-up among 1304 participants with type 1 diabetes in the prospective DCCT/EDIC Study. In summary, we identified a missense CUBN variant that associates with levels of albuminuria in both the general population and in individuals with diabetes

  • 35. Capiau, Sara
    et al.
    Veenhof, Herman
    Koster, Remco
    Bergqvist, Yngve
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Boettcher, Michael
    Halmingh, Otto
    Keevil, Brian
    Koch, Birgit
    Linden, Rafael
    Alffenaar, Jan-Willem
    Official International Association for Therapeutic Drug Monitoring and Toxicology guideline: Development and Validation of Dried Blood Spot-based Methods for Therapeutic Drug Monitoring2019Ingår i: Therapeutic Drug Monitoring, ISSN 0163-4356, E-ISSN 1536-3694, Vol. 41, nr 4, s. 409-430Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Dried blood spot (DBS) analysis has been introduced more and more into clinical practice to facilitate Therapeutic Drug Monitoring (TDM). To assure the quality of bioanalytical methods, the design, development and validation needs to fit the intended use. Current validation requirements, described in guidelines for traditional matrices (blood, plasma, serum), do not cover all necessary aspects of method development, analytical- and clinical validation of DBS assays for TDM. Therefore, this guideline provides parameters required for the validation of quantitative determination of small molecule drugs in DBS using chromatographic methods, and to provide advice on how these can be assessed. In addition, guidance is given on the application of validated methods in a routine context. First, considerations for the method development stage are described covering sample collection procedure, type of filter paper and punch size, sample volume, drying and storage, internal standard incorporation, type of blood used, sample preparation and prevalidation. Second, common parameters regarding analytical validation are described in context of DBS analysis with the addition of DBS-specific parameters, such as volume-, volcano-and hematocrit effects. Third, clinical validation studies are described, including number of clinical samples and patients, comparison of DBS with venous blood, statistical methods and interpretation, spot quality, sampling procedure, duplicates, outliers, automated analysis methods and quality control programs. Lastly, cross-validation is discussed, covering changes made to existing sampling- and analysis methods. This guideline of the International Association of Therapeutic Drug Monitoring and Clinical Toxicology on the development, validation and evaluation of DBS-based methods for the purpose of TDM aims to contribute to high-quality micro sampling methods used in clinical practice.

  • 36. Carlsson, A. C.
    et al.
    Riserus, U.
    Engstrom, G.
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Melander, O.
    Leander, K.
    Gigante, B.
    Hellenius, M-L
    de Faire, U.
    Novel and established anthropometric measures and the prediction of incident cardiovascular disease: a cohort study2013Ingår i: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 37, nr 12, s. 1579-1585Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVES: The aim of this study was to compare novel and established anthropometrical measures in their ability to predict cardiovascular disease (CVD), and to determine whether they improve risk prediction beyond classical risk factors in a cohort study of 60-year-old men and women. We also stratified the results according to gender to identify possible differences between men and women. Furthermore, we aimed to replicate our findings in a large independent cohort (The Malmo Diet and Cancer study-cardiovascular cohort).

    METHODS: This was a population-based study of 1751 men and 1990 women, aged 60 years and without CVD at baseline, with 375 incident cases of CVD during 11 years of follow-up. Weight, height, waist circumference (WC), hip circumference and sagittal abdominal diameter (SAD) were measured at baseline. Body mass index (BMI), waist-hip ratio (WHR), waist-hip-height ratio (WHHR), WC-to-height ratio (WCHR) and SAD-to-height ratio (SADHR) were calculated.

    RESULTS: All anthropometric measures predicted CVD in unadjusted Cox regression models per s.d. increment (hazard ratios, 95% confidence interval), while significant associations after adjustments for established risk CVD factors were noted for WHHR 1.20 (1.08-1.33), WHR 1.14 (1.02-1.28), SAD 1.13 (1.02-1.25) and SADHR 1.17 (1.06-1.28). WHHR had higher increases in C-statistics, and model improvements (likelihood ratio tests (P<0.001)). In the replication study (MDC-CC, n = 5180), WHHR was the only measure that improved Cox regression models in men (P = 0.01).

    CONCLUSION: WHHR, a new measure reflecting body fat distribution, showed the highest risk estimates after adjustments for established CVD risk factors. These findings were verified in men but not women in an independent cohort.

  • 37.
    Carlsson, A C
    et al.
    Division of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden ; Centre for Family Medicine, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden.
    Riserus, Ulf
    Clinical Nutrition and Metabolism, Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden.
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Department of Public Health and Caring Sciences/Section of Geriatrics Uppsala University, Uppsala, Sweden.
    Borné, Y
    Department of Clinical Sciences, Lund University, Malmö, Sweden.
    Leander, K
    Division of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Gigante, B
    Division of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden ; Clinical Nutrition and Metabolism, Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden.
    Hellénius, M-L
    Cardiology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
    Bottai, M
    Division of Biostatistics, Institute of Environmental Medicine, Karolinska Institute, Sweden.
    de Faire, U
    Division of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden ; Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden.
    Prediction of cardiovascular disease by abdominal obesity measures is dependent on body weight and sex: results from two community based cohort studies2014Ingår i: NMCD. Nutrition Metabolism and Cardiovascular Diseases, ISSN 0939-4753, E-ISSN 1590-3729, Vol. 24, nr 8, s. 891-899Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    AIM: To study waist-hip ratio (WHR), waist circumference (WC), sagittal abdominal diameter (SAD), and waist-hip-height ratio (WHHR) as predictors of CVD, in men and women stratified by BMI (cut-off ≥25).

    METHODS AND RESULTS: A cohort of n = 3741 (53% women) 60-year old individuals without CVD was followed for 11-years (375 CVD cases). To replicate the results, we also assessed another large independent cohort; The Malmö Diet and Cancer study - cardiovascular cohort (MDCC, (n = 5180, 60% women, 602 CVD cases during 16-years). After adjustment for established risk factors in normal-weight women, the hazard ratio (HR) per one standard deviation (SD) were; WHR; 1.91 (95% confidence interval (CI) 1.35-2.70), WC; 1.81 (95% CI 1.02-3.20), SAD; 1.25 (95% CI 0.74-2.11), and WHHR; 1.97 (95% CI 1.40-2.78). In men the association with WHR, WHHR and WC were not significant, whereas SAD was the only measure that significantly predicted CVD in men (HR 1.19 (95% CI 1.04-1.35). After adjustments for established risk factors in overweight/obese women, none of the measures were significantly associated with CVD risk. In men, however, all measures were significant predictors; WHR; 1.24 (955 CI 1.04-1.47), WC 1.19 (95% CI 1.00-1.42), SAD 1.21 (95% CI 1.00-1.46), and WHHR; 1.23 (95% CI 1.05-1.44). Only the findings in men with BMI ≥ 25 were verified in MDCC.

    CONCLUSION: In normal weight individuals, WHHR and WHR were the best predictors in women, whereas SAD was the only independent predictor in men. Among overweight/obese individuals all measures failed to predict CVD in women, whereas WHHR was the strongest predictor after adjustments for CVD risk factors in men.

  • 38. Carlsson, A. C.
    et al.
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Uppsala universitet.
    Sundström, J.
    Michaëlsson, K.
    Byberg, L.
    Lind, L.
    Physical activity, obesity and risk of cardiovascular disease in middle-aged men during a median of 30 years of follow-up2016Ingår i: European Journal of Preventive Cardiology, ISSN 2047-4873, E-ISSN 2047-4881, Vol. 23, nr 4, s. 359-365Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: We aimed to investigate associations between combinations of body mass index (BMI)-categories, levels of physical activity and long-term risk of cardiovascular disease.

    Method and results: At age 50 years, cardiovascular risk factors were assessed in 2196 participating men of the ULSAM-study. This investigation was repeated at age 60, 70, 77 and 82 years. Being physically active (PA) was defined as three hours of recreational or hard physical training per week. The men were categorized according to BMI/PA-status, as PA/normal weight (n = 593 at baseline), non-PA/normal weight (BMI &lt; 25 kg/m2, n = 580), PA/overweight (n = 418), non-PA/overweight (BMI 25-30 kg/m2, n = 462), PA/obese (n = 62), non-PA/obese (BMI &gt;30 kg/m2, n = 81). We used updated data on BMI and physical activity obtained at all examinations. During follow-up (median 30 years) 850 individuals suffered a cardiovascular disease (myocardial infarction, stroke or heart failure). Using updated data on BMI/PA categories, an increased risk for cardiovascular disease was seen with increasing BMI, but a high physical activity was associated with a lower risk of cardiovascular disease within each BMI category: non-PA/normal weight (hazard ratio (HR) 1.31, 95% confidence interval (CI) 1.04-1.66), PA/overweight (HR 1.52, 95% CI 1.20-1.94), non-PA/overweight (HR 1.65, 95% CI 1.31-2.07) PA/obese (HR 2.05, 95% CI 1.44-2.92) and non-PA/obese (HR 2.39, 95% CI 1.74-3.29), using PA/normal weight men as referent.

    Conclusions: Although physical activity was beneficial at all levels of BMI regarding the risk of future cardiovascular disease, there was still a substantial increased risk associated with being overweight or obese during 30 years of follow-up. 

  • 39. Carlsson, A C
    et al.
    Östgren, C J
    Länne, T
    Larsson, A
    Nystrom, F H
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Uppsala universitet.
    The association between endostatin and kidney disease and mortality in patients with type 2 diabetes2016Ingår i: Diabetes & Metabolism, ISSN 1262-3636, E-ISSN 1878-1780, Vol. 42, nr 5, s. 351-357Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    AIM: Circulating endostatin, a biologically active derivate of collagen XVIII, is considered to be a marker of kidney disease and a risk factor for its related mortality. However, less is known of the role of endostatin in diabetes and the development of diabetic nephropathy. For this reason, our study investigated the associations between circulating endostatin and the prevalence and progression of kidney disease, and its mortality risk in patients with type 2 diabetes (T2D).

    METHODS: This was a cohort study of 607 patients with T2D (mean age: 61 years, 44% women). Estimated glomerular filtration rate (eGFR), calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation, was used to assess the patients' kidney function decline and mortality.

    RESULTS: Of the total study cohort, 20 patients declined by ≥20% in eGFR over 4 years, and 44 died during the follow-up (mean duration: 6.7 years). At baseline, participants with diabetic nephropathy (defined as eGFR<60mL/min/1.73m(2)) and/or microalbuminuria [defined as a urinary albumin-to-creatinine ratio (ACR)>3g/mol] had higher median levels of endostatin than those without nephropathy (62.7μg/L vs 57.4μg/L, respectively; P=0.031). In longitudinal analyses adjusted for age, gender, baseline eGFR and ACR, higher endostatin levels were associated with a higher risk of decline (≥20% in eGFR, OR per 1 SD increase: 1.73, 95% CI: 1.13-2.65) and a higher risk of mortality (HR per 1 SD increase: 1.57, 95% CI: 1.19-2.07).

    CONCLUSION: In patients with T2D, circulating endostatin levels can predict the progression of kidney disease and mortality independently of established kidney disease markers. The clinical usefulness of endostatin as a risk marker in such patients merits further studies.

  • 40.
    Carlsson, Axel C
    et al.
    Centre for Family Medicine, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden ; Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
    Calamia, Michael
    Landstinget Dalarna, Falun, Sweden.
    Risérus, Ulf
    Department of Public Health and Caring Sciences/Section of Clinical Nutrition and Metabolism, Uppsala University, Uppsala, Sweden.
    Larsson, Anders
    Department of Medical Sciences, Uppsala University Hospital, Uppsala, Sweden.
    Helmersson-Karlqvist, Johanna
    Department of Medical Sciences, Uppsala University Hospital, Uppsala, Sweden.
    Lind, Lars
    Department of Medical Sciences, Uppsala University Hospital, Uppsala, Sweden.
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
    Kidney injury molecule (KIM)-1 is associated with insulin resistance: results from two community-based studies of elderly individuals2014Ingår i: Diabetes Research and Clinical Practice, ISSN 0168-8227, E-ISSN 1872-8227, Vol. 103, nr 3, s. 516-21Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND AND OBJECTIVES: Insulin resistance has been shown to be closely associated with glomerular filtration rate and urinary albumin/creatinine ratio, even prior to the development of diabetes. Urinary kidney injury molecule 1 (KIM-1) is a novel, highly specific marker of kidney tubular damage. The role of insulin resistance in the development of kidney tubular damage is not previously reported. Thus, we aimed to investigate the associations between insulin sensitivity (assessed by HOMA) and urinary KIM-1.

    DESIGN, SETTING, PARTICIPANTS AND MEASUREMENTS: Two community-based cohorts of elderly individuals were investigated: Prospective Investigation of the vasculature in Uppsala seniors (PIVUS, n=701; mean age 75 years, 52% women); and Uppsala Longitudinal Study of adult men (ULSAM, n=533; mean age 78 years).

    RESULTS: Lower insulin sensitivity was associated with higher urinary KIM-1 in both cohorts after adjustments for age, BMI, blood pressure, antihypertensive treatment, glomerular filtration rate, and urinary albumin-creatinine ratio (PIVUS: regression coefficient for 1-SD higher HOMA-IR 0.11, 95% CI 0.03-0.20, p=0.009, and ULSAM: 0.13, 95% CI 0.04-0.22, p=0.007). Results were similar in individuals without diabetes, with normal kidney function and normo-albuminuria.

    CONCLUSIONS: Our findings in elderly individuals support the notion that the interplay between an impaired glucose metabolism and renal tubular damage is evident even prior to the development of diabetes and overt kidney disease.

  • 41. Carlsson, Axel C.
    et al.
    Carrero, Juan-Jesus
    Stenvinkel, Peter
    Bottai, Matteo
    Barany, Peter
    Larsson, Anders
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Endostatin, cathepsin S, and cathepsin L, and their association with inflammatory markers and mortality in patients undergoing hemodialysis2015Ingår i: Blood Purification, ISSN 0253-5068, E-ISSN 1421-9735, Vol. 39, nr 4, s. 259-265Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background/Aims: Although both endostatin and cathepsins S have been associated with higher mortality, data in patients with end-stage renal disease (ESRD) are scarce.

    Methods: A longitudinal cohort study of 207 prevalent patients undergoing hemodialysis.

    Results: Cathepsins S and L were associated with soluble receptors for tumor necrosis factor (sTNFR1 and sTNFR2, rho between 0.28 and 0.43, p < 0.001 for all). Weaker or absent associations between endostatin, cathepsins S and L were seen with other inflammatory biomarkers, that is, CRP, interleukin 6, pentraxin 3, and TNF. In Cox and Laplace regression models adjusted for age, sex, dialysis vintage, and diabetes: standard deviation increments of endostatin was associated with a lower mortality (hazard ratio 0.75, 95% confidence interval (CI) 0.57-0.98), and with 6.8 months longer median survival.

    Conclusions: The high levels of endostatin, cathepsins S and L, and their associations with sTNFR1 and sTNFR2 warrant further studies exploring mortality, and the angiogenic and inflammatory pathways in ESRD. (C) 2015 S. Karger AG, Basel

  • 42. Carlsson, Axel C.
    et al.
    Carrero, Juan-Jesus
    Stenvinkel, Peter
    Bottai, Matteo
    Barany, Peter
    Larsson, Anders
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Uppsala universitet.
    High levels of soluble tumor necrosis factor receptors 1 and 2 and their association with mortality in patients undergoing hemodialysis2015Ingår i: CardioRenal Medicine, ISSN 1664-3828, Vol. 5, nr 2, s. 89-95Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: Circulating soluble tumor necrosis factor receptors 1 and 2 (sTNFR1 and 5TNFR2) are associated with chronic kidney disease (CKD) progression in patients with CKD or diabetes, and with higher mortality. However, data in patients with end-stage renal disease are scarce. Therefore, we analyzed serum levels of sTNFR1 and sTNFR2 and investigated their association with inflammatory markers and mortality in dialysis patients. Research Design and Methods: This was a longitudinal cohort study of 207 prevalent patients (median age 66 years, 56% men) undergoing hemodialysis in Stockholm, Sweden. Demographics, clinical characteristics, including comorbidities and laboratory data, were obtained at baseline, together with prospective follow-up for mortality.

    Results: The median sTNFR1 and sTNFR2 levels were 17,680 ng/l [95% confidence interval (CI) 17,023-18,337] and 24,450 ng/l (95% CI 23,721-25,179), respectively. During a follow-up of 31 months (interquartile range, 21-38), 77 patients died. There was no association between the levels of sTNFRs and mortality in Cox regression models, and no consistent trend towards higher or lower mortality was seen in Laplace regression models. sTNFR1 and sTNFR2 levels were highly associated with other inflammatory markers including interleukin-6, pentraxin 3 and TNF-alpha. Conclusions:Prevalent hemodialysis patients have several-fold higher levels of sTNFRs compared to previous studies in CKD stage 4 patients. As no consistent association between TNFR and mortality was observed, clinical implications of measuring these receptors to predict outcome end-stage renal disease patients provide limited results.

  • 43. Carlsson, Axel C
    et al.
    Ingelsson, Erik
    Sundström, Johan
    Carrero, Juan Jesus
    Gustafsson, Stefan
    Feldreich, Tobias
    Stenemo, Markus
    Larsson, Anders
    Lind, Lars
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Uppsala universitet.
    Use of proteomics to investigate kidney function decline over 5 years2017Ingår i: American Society of Nephrology. Clinical Journal, ISSN 1555-9041, E-ISSN 1555-905X, Vol. 12, nr 8, s. 1226-1235Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND AND OBJECTIVES: Using a discovery/replication approach, we investigated associations between a multiplex panel of 80 circulating proteins associated with cardiovascular pathology or inflammation, and eGFR decline per year and CKD incidence.

    DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We used two cohorts, the Prospective Investigation of the Vasculature in Uppsala Seniors Study (PIVUS; n=687, mean age of 70 years, 51% women) and the Uppsala Longitudinal Study of Adult Men (ULSAM; n=360 men, mean age of 78 years), with 5-year follow-up data on eGFR. There were 231 and 206 incident cases of CKD during follow-up in the PIVUS and ULSAM studies, respectively. Proteomic profiling of 80 proteins was assessed by a multiplex assay (proximity extension assay). The assay uses two antibodies for each protein and a PCR step to achieve a high-specific binding and the possibility to measure multiple proteins in parallel, but gives no absolute concentrations.

    RESULTS: In the discovery cohort from the PIVUS Study, 28 plasma proteins were significantly associated with eGFR decline per year, taking into account the multiple testing. Twenty of these proteins were significantly associated with eGFR decline per year in the replication cohort from the ULSAM Study after adjustment for age, sex, cardiovascular risk factors, medications, and urinary albumin-to-creatinine ratio (in order of significance: TNF-related apoptosis-inducing ligand receptor 2*, CD40L receptor, TNF receptor 1*, placenta growth factor*, thrombomodulin*, urokinase plasminogen activator surface receptor*, growth/differentiation factor 15*, macrophage colony-stimulating factor 1, fatty acid-binding protein*, cathepsin D, resistin, kallikrein 11*, C-C motif chemokine 3, proteinase-activated receptor 1*, cathepsin L, chitinase 3-like protein 1, TNF receptor 2*, fibroblast growth factor 23*, monocyte chemotactic protein 1, and kallikrein 6). Moreover, 11 of the proteins predicted CKD incidence (marked with * above). No protein consistently predicted eGFR decline per year independently of baseline eGFR in both cohorts.

    CONCLUSIONS: Several circulating proteins involved in phosphate homeostasis, inflammation, apoptosis, extracellular matrix remodeling, angiogenesis, and endothelial dysfunction were associated with worsening kidney function. Multiplex proteomics appears to be a promising way of discovering novel aspects of kidney disease pathology.

  • 44. Carlsson, Axel C
    et al.
    Jansson, Jan-Håkan
    Söderberg, Stefan
    Ruge, Toralph
    Larsson, Anders
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Levels of soluble tumor necrosis factor receptor 1 and 2, gender, and risk of myocardial infarction in Northern Sweden2018Ingår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 272, s. 41-46Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND AND AIMS: Soluble receptors for tumor necrosis factor alpha (sTNFR1 and sTNFR2) have been associated with cardiovascular diseases, and some evidence points towards a difference in associated risk between men and women. We aimed to study the association between sTNFR1 and sTNFR2 and incident myocardial infarctions (MI) and to explore the influence of established cardiovascular risk factors in men and women.

    METHODS: We conducted a nested case control study in three large Swedish cohorts, including 533 myocardial infarction cases, and 1003 age-, sex- and cohort-matched controls. Odds ratios (OR) with 95% confidence intervals (CI) were calculated.

    RESULTS: An association between circulating sTNFR1 and sTNFR2 and an increased risk for MI was found when comparing cases and controls. The odds ratios were significant after adjustment for established cardiovascular risk factors and C-reactive protein in women (OR 1.44, 95% CI 1.08-1.93 for TNFR1, and 1.61, 95% CI 1.11-2.34 for TNFR2), but was abolished in men. Women with a combination of elevated CRP and values in the upper quartile of TNFR1 or TNFR2 had a 5-fold higher risk of myocardial infarction versus those with normal CRP and values in the lower three quartiles of TNFR1 or TNFR2.

    CONCLUSIONS: As the risk estimates for TNFR1 and TNFR2 were higher and remained significant after adjustments for established cardiovascular risk factors in women but not in men, a potential role for TNFR1 and TNFR2 in identifying women with a higher MI risk is possible. The future clinical role of TNFR1 and TNFR2 in combination with CRP to identify high risk patients for coronary heart disease has yet to be determined.

  • 45. Carlsson, Axel C
    et al.
    Juhlin, C Christofer
    Larsson, Tobias E
    Larsson, Anders
    Ingelsson, Erik
    Sundström, Johan
    Lind, Lars
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Uppsala universitet.
    Soluble tumor necrosis factor receptor 1 (sTNFR1) is associated with increased total mortality due to cancer and cardiovascular causes: findings from two community based cohorts of elderly2014Ingår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 237, nr 1, s. 236-242Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Experimental evidence support soluble receptors for tumor necrosis factor alpha as important mediators of the underlying pathology leading to cardiovascular disease and cancer. However, prospective data concerning the relation between circulating soluble tumor necrosis factor receptor-1 (sTNFR1) and mortality in humans are lacking. We aimed to explore and validate the association between sTNFR1 and mortality, and to explore the influence of other established risk factors for mortality, including other inflammatory markers.

    METHODS: The association between serum sTNFR1and the risk for mortality was investigated in two community-based cohorts of elderly: the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS; women 50%, n = 1005, mean age 70 years, median follow-up 7.9 years) and the Uppsala Longitudinal Study of Adult Men (ULSAM, n = 775, mean age 77 years, median follow-up 8.1 years).

    RESULTS: In total, 101 participants in PIVUS and 274 in ULSAM died during follow-up. In multivariable Cox regression models adjusted for inflammation, lifestyle and established cardiovascular risk factors, one standard deviation (SD) higher sTNFR1 was associated with a hazard ratio (HR) for mortality of 1.37, 95% confidence interval (CI) 1.17-1.60, in PIVUS and HR 1.22, 95% CI 1.10-1.37 in ULSAM. Moreover, circulatingsTNFR1 was associated with cardiovascular mortality (HR per SD of sTNFR1, 1.24, 95% CI 1.07-1.44) and cancer mortality (HR per SD of sTNFR1, 1.32, 95% CI 1.11-1.57) in the ULSAM cohort. High levels of sTNFR1 identified individuals with increased risk of mortality among those with high as well as low levels of systemic inflammation.

    CONCLUSIONS: An association between circulating sTNFR1 and an increased risk for mortality was found and validated in two independent community-based cohorts. The future clinical role of sTNFR1 to identify high risk patients for adverse outcomes and mortality has yet to be determined.

  • 46.
    Carlsson, Axel C
    et al.
    Centre for Family Medicine, Department of Neurobiology, Care Sciences, and Society, Karolinska Institute, Huddinge, Sweden; Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
    Larsson, Anders
    Department of Medical Sciences, Uppsala University Hospital, Uppsala, Sweden.
    Helmersson-Karlqvist, Johanna
    Department of Medical Sciences, Uppsala University Hospital, Uppsala, Sweden.
    Lind, Lars
    Department of Medical Sciences, Uppsala University Hospital, Uppsala, Sweden.
    Ingelsson, Erik
    Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
    Larsson, Tobias E
    Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
    Bottai, Matteo
    Division of Biostatistics, Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden.
    Sundström, Johan
    Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
    Urinary kidney injury molecule-1 and the risk of cardiovascular mortality in elderly men2014Ingår i: American Society of Nephrology. Clinical Journal, ISSN 1555-9041, E-ISSN 1555-905X, Vol. 9, nr 8, s. 1393-1401Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND AND OBJECTIVES: Kidney injury molecule-1 (KIM-1) has been suggested as a clinically relevant highly specific biomarker of acute kidney tubular damage. However, community-based data on the association between urinary levels of KIM-1 and the risk for cardiovascular mortality are lacking. This study aimed to investigate the association between urinary KIM-1 and cardiovascular mortality.DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This was a prospective study, using the community-based Uppsala Longitudinal Study of Adult Men (N=590; mean age 77 years; baseline period, 1997-2001; median follow-up 8.1 years; end of follow-up, 2008).RESULTS: During follow-up, 89 participants died of cardiovascular causes (incidence rate, 2.07 per 100 person-years at risk). Models were adjusted for cardiovascular risk factors (age, systolic BP, diabetes, smoking, body mass index, total cholesterol, HDL cholesterol, antihypertensive treatment, lipid-lowering treatment, aspirin treatment, and history of cardiovascular disease) and for markers of kidney dysfunction and damage (cystatin C-based eGFR and urinary albumin/creatinine ratio). Higher urinary KIM-1/creatinine (from 24-hour urine collections) was associated with a higher risk for cardiovascular mortality (hazard ratio per SD increase, 1.27; 95% confidence interval [95% CI], 1.05 to 1.54; P=0.01). Participants with a combination of high KIM-1/creatinine (upper quintile, ≥175 ng/mmol), low eGFR (≤60 ml/min per 1.73 m(2)), and microalbuminuria/macroalbuminuria (albumin/creatinine ratio≥3 g/mol) had a >8-fold increased risk compared with participants with low KIM-1/creatinine (<175 ng/mmol), normal eGFR (>60 ml/min per 1.73 m(2)), and normoalbuminuria (albumin/creatinine ratio<3 g/mol) (hazard ratio, 8.56; 95% CI, 4.17 to 17.56; P<0.001).CONCLUSIONS: These findings suggest that higher urinary KIM-1 may predispose to a higher risk of cardiovascular mortality independently of established cardiovascular risk factors, eGFR, and albuminuria. Additional studies are needed to further assess the utility of measuring KIM-1 in the clinical setting.

  • 47. Carlsson, Axel C
    et al.
    Larsson, Anders
    Helmersson-Karlqvist, Johanna
    Lind, Lars
    Ingelsson, Erik
    Larsson, Tobias E
    Sundström, Johan
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Urinary kidney injury molecule 1 and incidence of heart failure in elderly men2013Ingår i: European Journal of Heart Failure, ISSN 1388-9842, E-ISSN 1879-0844, Vol. 15, nr 4, s. 447-446Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    AIMS: There is growing recognition of the clinical importance of cardiorenal syndrome-the bidirectional interplay between kidney and cardiac dysfunction. Yet, the role of kidney tubular damage in the development of heart failure is less studied. The objective of this study was to investigate whether urinary kidney injury molecule (KIM)-1, a specific marker of tubular damage, predisposes to an increased heart failure risk.

    METHODS AND RESULTS: This was a community-based cohort study [Uppsala Longitudinal study of Adult Men (ULSAM)] of 565, 77-year-old men free from heart failure at baseline. Heart failure hospitalizations were used as outcome. During follow-up (median 8.0 years), 73 participants were hospitalized for heart failure. In models adjusted for cardiovascular risk factors (age, systolic blood pressure, diabetes, smoking, body mass index, LDL/HDL ratio, antihypertensive treatment, lipid-lowering treatment, aspirin treatment, LV hypertrophy, and prevalent cardiovascular disease) and markers of kidney dysfunction and damage [cystatin C-based glomerular filtration rate (GFR) and urinary albumin/creatinine ratio], a higher urinary KIM-1/creatinine ratio was associated with higher risk for heart failure (hazard ratio upper vs. lower tertile, 1.81; 95% confidence interval 1.01-3.29; P < 0.05). Participants with a combination of low GFR (<60 mL/min/1.72 m(2)) and high KIM-1/creatinine (>128 ng/mmol) had a 3-fold increase in heart failure risk compared with participants with normal GFR and KIM-1 (P < 0.001).

    CONCLUSION: Our findings suggest that kidney tubular damage predisposes to an increased risk for heart failure in the community. Further studies are needed to clarify the causal role of KIM-1 in the development of heart failure, and to evaluate the clinical utility of urinary KIM-1 measurements.

  • 48.
    Carlsson, Axel C
    et al.
    Centre for Family Medicine, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden ; Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
    Larsson, Tobias E
    Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
    Helmersson-Karlqvist, Johanna
    Department of Medical Sciences, Uppsala University Hospital, Uppsala, Sweden.
    Larsson, Anders
    Department of Medical Sciences, Uppsala University Hospital, Uppsala, Sweden.
    Lind, Lars
    Department of Medical Sciences, Uppsala University Hospital, Uppsala, Sweden.
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
    Soluble TNF receptors and kidney dysfunction in the elderly2014Ingår i: Journal of the American Society of Nephrology, ISSN 1046-6673, E-ISSN 1533-3450, Vol. 25, nr 6, s. 1313-1320Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The importance of TNF-α and its soluble receptors (sTNFR1 and sTNFR2) in the development of kidney disease is being unraveled. Yet, community-based data regarding the role of sTNFRs are lacking. We assessed serum sTNFRs and aspects of kidney damage cross-sectionally in two independent community-based cohorts of elderly participants: Prospective Investigation of the Vasculature in Uppsala Seniors (n=815; mean age, 75 years; 51% women) and Uppsala Longitudinal Study of Adult Men (n=778; mean age, 78 years). Serum sTNFR1 correlated substantially with different aspects of kidney pathology in the Uppsala Longitudinal Study of Adult Men cohort (R=-0.52 for estimated GFR, R=0.22 for urinary albumin-to-creatinine ratio, and R=0.17 for urinary kidney injury molecule-1; P<0.001 for all), with similar correlations in the Prospective Investigation of the Vasculature in Uppsala Seniors cohort. These associations remained significant after adjustment for age, sex, inflammatory markers, and cardiovascular risk factors and were also evident in participants without diabetes. Serum sTNFR2 was associated with all three markers in the Prospective Investigation of the Vasculature in Uppsala Seniors cohort (P<0.001 for all). Our findings from two independent community-based cohorts confirm and extend results of previous studies supporting circulating sTNFRs as relevant biomarkers for kidney damage and dysfunction in elderly individuals, even in the absence of diabetes.

  • 49. Carlsson, Axel C
    et al.
    Li, Xinjun
    Holzmann, Martin J
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Karolinska Institute.
    Wändell, Per
    Gasevic, Danijela
    Sundquist, Jan
    Sundquist, Kristina
    Neighborhood socioeconomic status at the age of 40 years and ischemic stroke before the age of 50 years: A nationwide cohort study from Sweden.2017Ingår i: International Journal of Stroke, ISSN 1747-4930, E-ISSN 1747-4949, Vol. 12, nr 8, s. 815-826Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: We aimed to study the association between neighborhood socioeconomic status at the age of 40 years and risk of ischemic stroke before the age of 50 years.

    Methods: All individuals in Sweden were included if their 40th birthday occurred between 1998 and 2010. National registers were used to categorize neighborhood socioeconomic status into high, middle, and low and to retrieve information on incident ischemic strokes. Hazard ratios and their 95% confidence intervals were estimated.

    Results: A total of 1,153,451 adults (women 48.9%) were followed for a mean of 5.5 years (SD 3.5 years), during which 1777 (0.30%) strokes among men and 1374 (0.24%) strokes among women were recorded. After adjustment for sex, marital status, education level, immigrant status, region of residence, and neighborhood services, there was a lower risk of stroke in residents from high-socioeconomic status neighborhoods (hazard ratio 0.87, 95% confidence interval 0.78-0.96), and an increased risk of stroke in adults from low-socioeconomic status neighborhoods (hazard ratio 1.16, 95% confidence interval 1.06-1.27), compared to their counterparts living in middle-socioeconomic status neighborhoods. After further adjustment for hospital diagnoses of hypertension, diabetes, heart failure, and atrial fibrillation prior to the age of 40, the higher risk in neighborhoods with low socioeconomic status was attenuated, but remained significant (hazard ratio 1.12, 95% confidence interval 1.02-1.23).

    Conclusions: In a nationwide study of individuals between 40 and 50 years, we found that the risk of ischemic stroke differed depending on neighborhood socioeconomic status, which calls for increased efforts to prevent cardiovascular diseases in low socioeconomic status neighborhoods.

  • 50.
    Carlsson, Axel C.
    et al.
    Karolinska Institutet.
    Nordquist, Lina
    Uppsala Universitet.
    Larsson, Tobias E.
    Karolinska Institutet.
    Carrero, Juan-Jesus
    Karolinska Institutet.
    Larsson, Anders
    Uppsala Universitet.
    Lind, Lars
    Uppsala university hospital.
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Uppsala universitet.
    Soluble tumor necrosis factor receptor 1 is associated with glomerular filtration rate progression and incidence of chronic kidney disease in two community-based cohorts of elderly individuals2015Ingår i: CardioRenal Medicine, ISSN 1664-3828, Vol. 5, nr 4, s. 278-288Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: We aimed to explore and validate the longitudinal associations between soluble tumor necrosis factor receptor 1 (sTNFR1), glomerular filtration rate (GFR) progression, and chronic kidney disease (CKD) incidence in two independent community-based cohorts of elderly individuals with prespecified subgroup analyses in individuals without prevalent diabetes.

    Research design and methods: Two community-based cohorts of elderly individuals were used with 5-year follow-up data on estimated GFR: the Uppsala Longitudinal Study of Adult Men (ULSAM; n = 437 men; mean age: 78 years) and the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS; n = 703; mean age: 70 years; 51% women). GFR categories were defined as >= 60, 30-60, and <30 ml/min/1.73 m(2).

    Results: In longitudinal multivariable logistic regression models adjusted for inflammatory markers and established cardiovascular risk factors, higher serum sTNFR1 was significantly associated with an increased risk to progress to a lower GFR category in both ULSAM and PIVUS [odds ratio (OR) per standard deviation (SD) increase 1.28 (95% CI 1.03-1.60) and OR 1.56 (95% CI 1.30-1.87), respectively]. Also, in subgroup analyses in individuals with a GFR >= 60 ml/min/1.73 m(2) at baseline, higher sTNFRs were associated with incident CKD after 5 years in both cohorts [ULSAM: OR per SD increase 1.49 (95% CI 1.16-1.9) and PIVUS: OR 1.84 (95% CI 1.50-2.26)]. Associations were similar in individuals without diabetes.

    Conclusions: Higher circulating sTNFR1 independently predicts the progression to a worse GFR category and CKD incidence in elderly individuals even in the absence of diabetes. Further studies are warranted to investigate the underlying mechanisms, and to evaluate the clinical relevance of our findings. 

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