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  • 251. Ngasala, Billy E.
    et al.
    Malmberg, Maja
    Carlsson, Anja M.
    Ferreira, Pedro E.
    Petzold, Max G.
    Blessborn, Daniel
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Bergqvist, Yngve
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Gil, Jose P.
    Premji, Zul
    Martensson, Andreas
    Effectiveness of artemether-lumefantrine provided by community health workers in under-five children with uncomplicated malaria in rural Tanzania: an open label prospective study2011Ingår i: Malaria Journal, ISSN 1475-2875, E-ISSN 1475-2875, Vol. 10, artikel-id 64Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Home-management of malaria (HMM) strategy improves early access of anti-malarial medicines to high-risk groups in remote areas of sub-Saharan Africa. However, limited data are available on the effectiveness of using artemisinin-based combination therapy (ACT) within the HMM strategy. The aim of this study was to assess the effectiveness of artemether-lumefantrine (AL), presently the most favoured ACT in Africa, in under-five children with uncomplicated Plasmodium falciparum malaria in Tanzania, when provided by community health workers (CHWs) and administered unsupervised by parents or guardians at home.

    Methods: An open label, single arm prospective study was conducted in two rural villages with high malaria transmission in Kibaha District, Tanzania. Children presenting to CHWs with uncomplicated fever and a positive rapid malaria diagnostic test (RDT) were provisionally enrolled and provided AL for unsupervised treatment at home. Patients with microscopy confirmed P. falciparum parasitaemia were definitely enrolled and reviewed weekly by the CHWs during 42 days. Primary outcome measure was PCR corrected parasitological cure rate by day 42, as estimated by Kaplan-Meier survival analysis. This trial is registered with ClinicalTrials.gov, number NCT00454961.

    Results: A total of 244 febrile children were enrolled between March-August 2007. Two patients were lost to follow up on day 14, and one patient withdrew consent on day 21. Some 141/241 (58.5%) patients had recurrent infection during follow-up, of whom 14 had recrudescence. The PCR corrected cure rate by day 42 was 93.0% (95% CI 88.3%-95.9%). The median lumefantrine concentration was statistically significantly lower in patients with recrudescence (97 ng/mL [IQR 0-234]; n = 10) compared with reinfections (205 ng/mL [114-390]; n = 92), or no parasite reappearance (217 [121-374] ng/mL; n = 70; p <= 0.046).

    Conclusions: Provision of AL by CHWs for unsupervised malaria treatment at home was highly effective, which provides evidence base for scaling-up implementation of HMM with AL in Tanzania.

  • 252. Nilsson, Erik
    et al.
    Rudholm Feldreich, Tobias
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Uppsala universitet.
    Stenvinkel, Peter
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Karolinska institutet.
    Pregnancy-associated plasma protein A and mortality in hemodialysis2018Ingår i: European Journal of Clinical Investigation, ISSN 0014-2972, E-ISSN 1365-2362, Vol. 48, nr 8, artikel-id e12959Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Elevated pregnancy-associated plasma protein A (PAPP-A) levels are associated with increased risk of death in ischemic heart disease as well as in hemodialysis patients. Previous research indicates that the prognostic value of PAPP-A may be stronger in patients with concomitant diabetes mellitus or signs of inflammation. We studied the association between PAPP-A and outcomes in prevalent hemodialysis patients and hypothesized that diabetes mellitus and inflammation status act as effect modifiers.

    MATERIALS AND METHODS: Circulating PAPP-A levels were quantified using ELISA. Cox proportional hazards- and quantile regression models were used for associations between PAPP-A and mortality. PAPP-A levels were log-transformed for Normality.

    RESULTS: During 60 months follow-up, 37 (40%) of the 92 participants died. Higher PAPP-A was associated with increased risk of mortality in unadjusted analysis (HR per SD = 1.4, 95% CI = 1 - 1.9, p = 0.03) and when adjusted for confounders and cardiovascular risk factors (HR = 1.8, 95% CI = 1.18-2.73, p = 0.006). An interaction between PAPP-A levels and diabetes mellitus on mortality was found (HR for the multiplicative interaction term = 2.74 95% CI = 1.02-7.37, p = 0.05). In a quantile regression adjusted for age and sex, one SD increase of PAPP-A was associated with 22 months shorter estimated time until 25% of the patients died (95% CI -35 to -9.1 months).

    CONCLUSIONS: Increased PAPP-A levels are associated with higher all-cause mortality in prevalent hemodialysis patients with concomitant diabetes mellitus. 

  • 253. Nishiyama, Chika
    et al.
    Brown, Siobhan P.
    May, Susanne
    Iwami, Taku
    Koster, Rudolph W.
    Beesems, Stefanie G.
    Kuisma, Markku
    Salo, Ari
    Jacobs, Ian
    Strömsöe, Anneli
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Apples to apples or apples to oranges?: International variation in reporting of process and outcome of care for out-of-hospital cardiac arrest2014Ingår i: Resuscitation, ISSN 0300-9572, E-ISSN 1873-1570, Vol. 85, nr 11, s. 1599-1609Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives: Survival after out-of-hospital cardiac arrest (OHCA) varies between communities, due in part to variation in the methods of measurement. The Utstein template was disseminated to standardize comparisons of risk factors, quality of care, and outcomes in patients with OHCA. We sought to assess whether OHCA registries are able to collate common data using the Utstein template. A subsequent study will assess whether the Utstein factors explain differences in survival between emergency medical services (EMS) systems. Study design: Retrospective study.

    Setting: This retrospective analysis of prospective cohorts included adults treated for OHCA, regardless of the etiology of arrest. Data describing the baseline characteristics of patients, and the process and outcome of their care were grouped by EMS system, de-identified, and then collated. Included were core Utstein variables and timed event data from each participating registry. This study was classified as exempt from human subjects' research by a research ethics committee.

    Measurements and main results: Thirteen registries with 265 first-responding EMS agencies in 13 countries contributed data describing 125,840 cases of OHCA. Variation in inclusion criteria, definition, coding, and process of care variables were observed. Contributing registries collected 61.9% of recommended core variables and 42.9% of timed event variables. Among core variables, the proportion of missingness was mean 1.9 +/- 2.2%. The proportion of unknown was mean 4.8 +/- 6.4%. Among time variables, missingness was mean 9.0 +/- 6.3%.

    Conclusions: International differences in measurement of care after OHCA persist. Greater consistency would facilitate improved resuscitation care and comparison within and between communities.

  • 254. Nowak, Christoph
    et al.
    Hetty, Susanne
    Salihovic, Samira
    Castillejo-Lopez, Casimiro
    Ganna, Andrea
    Cook, Naomi L
    Broeckling, Corey D
    Prenni, Jessica E
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Karolinska institutet.
    Ingelsson, Erik
    Glucose challenge metabolomics implicates medium-chain acylcarnitines in insulin resistance2018Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, nr 1, artikel-id 8691Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Insulin resistance (IR) predisposes to type 2 diabetes and cardiovascular disease but its causes are incompletely understood. Metabolic challenges like the oral glucose tolerance test (OGTT) can reveal pathogenic mechanisms. We aimed to discover associations of IR with metabolite trajectories during OGTT. In 470 non-diabetic men (age 70.6 ± 0.6 years), plasma samples obtained at 0, 30 and 120 minutes during an OGTT were analyzed by untargeted liquid chromatography-mass spectrometry metabolomics. IR was assessed with the hyperinsulinemic-euglycemic clamp method. We applied age-adjusted linear regression to identify metabolites whose concentration change was related to IR. Nine trajectories, including monounsaturated fatty acids, lysophosphatidylethanolamines and a bile acid, were significantly associated with IR, with the strongest associations observed for medium-chain acylcarnitines C10 and C12, and no associations with L-carnitine or C2-, C8-, C14- or C16-carnitine. Concentrations of C10- and C12-carnitine decreased during OGTT with a blunted decline in participants with worse insulin resistance. Associations persisted after adjustment for obesity, fasting insulin and fasting glucose. In mouse 3T3-L1 adipocytes exposed to different acylcarnitines, we observed blunted insulin-stimulated glucose uptake after treatment with C10- or C12-carnitine. In conclusion, our results identify medium-chain acylcarnitines as possible contributors to IR.

  • 255. Nowak, Christoph
    et al.
    Salihovic, Samira
    Ganna, Andrea
    Brandmaier, Stefan
    Tukiainen, Taru
    Broeckling, Corey D
    Magnusson, Patrik K
    Prenni, Jessica E
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Uppsala university.
    Fall, Tove
    Effect of insulin resistance on monounsaturated fatty acid levels: a multi-cohort non-targeted metabolomics and mendelian randomization study2016Ingår i: PLoS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 12, nr 10, artikel-id e1006379Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Insulin resistance (IR) and impaired insulin secretion contribute to type 2 diabetes and cardiovascular disease. Both are associated with changes in the circulating metabolome, but causal directions have been difficult to disentangle. We combined untargeted plasma metabolomics by liquid chromatography/mass spectrometry in three non-diabetic cohorts with Mendelian Randomization (MR) analysis to obtain new insights into early metabolic alterations in IR and impaired insulin secretion. In up to 910 elderly men we found associations of 52 metabolites with hyperinsulinemic-euglycemic clamp-measured IR and/or β-cell responsiveness (disposition index) during an oral glucose tolerance test. These implicated bile acid, glycerophospholipid and caffeine metabolism for IR and fatty acid biosynthesis for impaired insulin secretion. In MR analysis in two separate cohorts (n = 2,613) followed by replication in three independent studies profiled on different metabolomics platforms (n = 7,824 / 8,961 / 8,330), we discovered and replicated causal effects of IR on lower levels of palmitoleic acid and oleic acid. A trend for a causal effect of IR on higher levels of tyrosine reached significance only in meta-analysis. In one of the largest studies combining "gold standard" measures for insulin responsiveness with non-targeted metabolomics, we found distinct metabolic profiles related to IR or impaired insulin secretion. We speculate that the causal effects on monounsaturated fatty acid levels could explain parts of the raised cardiovascular disease risk in IR that is independent of diabetes development.

  • 256. Nowak, Christoph
    et al.
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Karolinska institutet.
    A Mendelian randomization study of the effects of blood lipids on breast cancer risk2018Ingår i: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 9, nr 1, artikel-id 3957Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Observational studies have reported inconsistent associations between circulating lipids and breast cancer risk. Using results from >400,000 participants in two-sample Mendelian randomization, we show that genetically raised LDL-cholesterol is associated with higher risk of breast cancer (odds ratio, OR, per standard deviation, 1.09, 95% confidence interval, 1.02-1.18, P = 0.020) and estrogen receptor (ER)-positive breast cancer (OR 1.14 [1.05-1.24] P = 0.004). Genetically raised HDL-cholesterol is associated with higher risk of ER-positive breast cancer (OR 1.13 [1.01-1.26] P = 0.037). HDL-cholesterol-raising variants in the gene encoding the target of CETP inhibitors are associated with higher risk of breast cancer (OR 1.07 [1.03-1.11] P = 0.001) and ER-positive breast cancer (OR 1.08 [1.03-1.13] P = 0.001). LDL-cholesterol-lowering variants mimicking PCSK9 inhibitors are associated (P = 0.014) with lower breast cancer risk. We find no effects related to the statin and ezetimibe target genes. The possible risk-promoting effects of raised LDL-cholesterol and CETP-mediated raised HDL-cholesterol have implications for breast cancer prevention and clinical trials.

  • 257.
    Nyberg, André
    et al.
    Umeå universitet, Institutionen för samhällsmedicin och rehabilitering.
    Tistad, Malin
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Umeå universitet, Institutionen för samhällsmedicin och rehabilitering.
    Wadell, Karin
    Umeå universitet, Institutionen för samhällsmedicin och rehabilitering.
    Can the COPD Web be used to promote self-management in patients with COPD in Swedish primary care: a controlled pragmatic pilot trial with 3 month and 12 month follow-up2019Ingår i: Scandinavian Journal of Primary Health Care, ISSN 0281-3432, E-ISSN 1502-7724Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE:

    Evaluate the feasibility of the COPD Web and its study design and study procedures and to increase the understanding of the potential effect of the tool in order to provide guidance for a future large scale trial.

    DESIGN:

    Parallel-group controlled pragmatic pilot trial.

    SUBJECTS:

    There was a total of 83 patients with COPD (mean age 70 ± 8 years with a forced expiratory volume in first second percent predicted of 60 ± 17%). The intervention group (n = 43) was introduced to and had access to the COPD Web in addition to usual care, while the control group (n = 40) received usual care alone.

    MAIN OUTCOME MEASURES:

    The feasibility of the COPD Web (i.e., if and how the COPD Web was used) was automatically collected through the website, while outcomes on health, conceptual knowledge, and physical activity (PA) were collected through questionnaires at baseline, 3 months and 12 months.

    RESULTS:

    At 3 months, 77% of the intervention group was considered users, and the majority of time spent on the site was related to PA and exercises and was spent during the first month (>80%). In addition, the intervention group reported increased PA (odds ratio [OR] = 4.4, P < .001), increased conceptual knowledge in five domains (OR = 2.6-4.2, all P < .05), and altered disease management strategies (e.g., increased PA) (OR ≥ 2.7 P < .05) in comparison to the control group. The latter was also different between groups at 12 months (OR = 3.7, P = .044). Knowledge of PA was correlated with level of PA (ρ = .425-.512, P < .05) as well as to the use of PA as a strategy to manage their disease (χ2 = 11.2-32.9, P < .05).

    CONCLUSION:

    Giving patients with COPD access to the COPD Web in addition to their ordinary primary care might be an effective shorter term (3 month) strategy to promote self-management. However, these results needs to be confirmed in a definitive large-scale trial. Key points Even though self-management strategies are an important part of chronic obstructive pulmonary disease (COPD) management, access to support for such strategies are limited for a large part of the COPD-population. Promoting self-management through the COPD Web might increase short-term levels of physical activity, promote conceptual knowledge and alter disease management strategies. The primary care COPD population in this study experienced limited impact of the disease in daily life, limited exertional dyspnea, and high generic quality-of-life, but vastly reduced levels of physical activity. A future large scale study should include strategies to encourage greater exposures to the COPD Web, including an extended analysis of factors associated with using or not using the tool over time and its impact on outcome measures, objective measures of conceptual knowledge, and physical activity, and it should include a large enough sample size to enable sub-group analyses and strategies to enhance recruitment.

  • 258. Nyberg, André
    et al.
    Wadell, Karin
    Lindgren, Helena
    Tistad, Malin
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Umeå universitet, Institutionen för samhällsmedicin och rehabilitering, Fysioterapin.
    Internet-based support for self-management strategies for people with COPD-protocol for a controlled pragmatic pilot trial of effectiveness and a process evaluation in primary healthcare2017Ingår i: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 7, nr 7, artikel-id e016851Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    INTRODUCTION: The use of adequate self-management strategies for people with chronic obstructive pulmonary disease (COPD) reduces healthcare use, improves health-related quality of life (HRQoL) and recovery after acute exacerbations. However, not many people with COPD receive support that promotes the use of such strategies and therefore new methods to facilitate and promote the use of self-management strategies are highly warranted. This pilot trial aims to evaluate the feasibility of the study design and study procedures considering effectiveness of the novel intervention, the COPD-web. METHODS AND ANALYSIS: The overall design is a pragmatic controlled pilot trial with preassessments and postassessments and a parallel process evaluation. Patients with the diagnosis of COPD will be eligible for the study. The intervention group will be recruited when visiting one of the six participating primary care units in Sweden. The control group will be identified from the unit's computerised registers. The intervention, the COPD-web, is an interactive web page with two sections; one directed at people with COPD and one at healthcare professionals. The sections aim to support patients' self-management skills-and to facilitate the provision of support for self-management strategies, respectively. Effectiveness with regard to patients' symptoms, HRQoL, knowledge of and readiness for COPD-related self-management, health literacy, self-efficacy for physical activity and time spent in physical activity and time being sedentary, and further, healthcare professionals' knowledge of and readiness to support COPD-related self-management strategies will be assessed using questionnaires at 3 and 12 months. The process evaluation will include observations and interviews.

    ETHICS AND DISSEMINATION: Ethical approval has been obtained. Findings will be presented at conferences, submitted for publication in peer-reviewed publications and presented to the involved healthcare professionals, patients and to patient organisations.

    TRIAL REGISTRATION NUMBER: ClinicalTrials.gov: NCT02696187.

  • 259. Nylander, Ruta
    et al.
    Lind, Lars
    Wikström, Johan
    Lindahl, Bertil
    Venge, Per
    Larsson, Anders
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Uppsala universitet.
    Berglund, Lars
    Ahlström, Håkan
    Larsson, Elna-Marie
    Relation between cardiovascular disease risk markers and brain infarcts detected by magnetic resonance imaging in an elderly population2015Ingår i: Journal of Stroke & Cerebrovascular Diseases, ISSN 1052-3057, E-ISSN 1532-8511, Vol. 24, nr 2, s. 312-318Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Established cardiovascular risk markers, such as hypertension, are associated with increased risk of brain infarcts. The newer markers N-terminal pro-brain natriuretic peptide, troponin I, C-reactive protein, and cystatin C may affect the risk of cardiovascular events and potentially, thereby, also stroke. We investigated the association between established and new risk markers for cardiovascular disease and brain infarcts detected by magnetic resonance imaging (MRI) at age 75.

    METHODS: Four hundred six randomly selected subjects from the Prospective Investigation of the Vasculature in Uppsala Seniors study were examined with MRI of the brain at age 75. Blood samples, measurements, and dedicated questionnaires at age 70 were used for analysis of risk markers. A history of diseases had been obtained at age 70 and 75. MRI was evaluated regarding lacunar and cortical infarcts. Univariate associations between outcomes and risk markers were assessed with logistic regression models.

    RESULTS: One or more infarcts were seen in 23% of the subjects (20% had only lacunar infarcts, 1% had only cortical infarcts, and 2% had both). Hypertension (odds ratio [OR] 2.6, 95% confidence interval [CI] 1.4, 4.7) and obesity (OR 1.3; CI 1.0, 1.8) were significantly associated with increased risk of brain infarction. The newer risk markers were not significantly associated with the brain infarcts.

    CONCLUSIONS: The new markers were not associated with the predominantly lacunar infarcts in our 75-year-old population, why troponin I and NT-proBNP may be associated mainly with cardioembolic infarcts as shown recently.

  • 260. Ohrmalm, Christina
    et al.
    Eriksson, Ronnie
    Jobs, Magnus
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Simonson, Magnus
    Stromme, Maria
    Bondeson, Kare
    Herrmann, Bjorn
    Melhus, Asa
    Blomberg, Jonas
    Variation-tolerant capture and multiplex detection of nucleic acids: application to detection of microbes2012Ingår i: Journal of Clinical Microbiology, ISSN 0095-1137, E-ISSN 1098-660X, Vol. 50, nr 10, s. 3208-3215Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In contrast to ordinary PCRs, which have a limited multiplex capacity and often return false-negative results due to target variation or inhibition, our new detection strategy, VOCMA (variation-tolerant capture multiplex assay), allows variation-tolerant, target-specific capture and detection of many nucleic acids in one test. Here we demonstrate the use of a single-tube, dual-step amplification strategy that overcomes the usual limitations of PCR multiplexing, allowing at least a 22-plex format with retained sensitivity. Variation tolerance was achieved using long primers and probes designed to withstand variation at known sites and a judicious mix of degeneration and universal bases. We tested VOCMA in situations where enrichment from a large sample volume with high sensitivity and multiplexity is important (sepsis; streptococci, enterococci, and staphylococci, several enterobacteria, candida, and the most important antibiotic resistance genes) and where variation tolerance and high multiplexity is important (gastroenteritis; astrovirus, adenovirus, rotavirus, norovirus genogroups I and II, and sapovirus, as well as enteroviruses, which are not associated with gastroenteritis). Detection sensitivities of 10 to 1,000 copies per reaction were achieved for many targets. VOCMA is a highly multiplex, variation-tolerant, general purpose nucleic acid detection concept. It is a specific and sensitive method for simultaneous detection of nucleic acids from viruses, bacteria, fungi, and protozoa, as well as host nucleic acid, in the same test. It can be run on an ordinary PCR and a Luminex machine and is suitable for both clinical diagnoses and microbial surveillance.

  • 261.
    Omer, Mohammed
    et al.
    Stockholm University.
    Klomsri, Tina
    Stockholm University.
    Tedre, Matti
    Stockholm University.
    Popova, Iskra
    Stockholm University.
    Klingberg-Allvin, Marie
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Omvårdnad.
    Osman, Fatumo
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Omvårdnad. Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    E-learning opens the door to the global community. Novice users experiences of e-learning in a Somali University2015Ingår i: Journal of Online Learning and Teaching, ISSN 1558-9528, E-ISSN 1558-9528, Vol. 11, nr 2Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    E-learning has become one of the primary ways of delivering education around the globe. In Somalia, which is a country torn within and from the global community by a prolonged civil war, University of Hargeisa has in collaboration with Dalarna University in Sweden adopted, for the first time, e-learning. This study explores barriers and facilitators to e-learning usage, experienced by students in Somalia’s higher education, using the University of Hargeisa as case study. Interviews were conducted with students to explore how University of Hargeisa’s novice users perceived elearning, and what factors positively and negatively affected their e-learning experiences. The Unified Theory of Acceptance and Use of Technology (UTAUT) model was used as a framework for interpreting the results. The findings show that, in general, the students have a very positive attitude towards e-learning, and they perceived that e-learning enhanced their educational experience. The communication aspect was found to be especially important for Somali students, as it facilitated a feeling of belonging to the global community of students and scholars and alleviated the war-torn country’s isolation. However, some socio-cultural aspects of students’ communities negatively affected their e-learning experience. This study ends with recommendations based on the empirical findings to promote the use and enhance the experience of e-learning in post conflict Somali educational institutions

  • 262.
    Osman, Fatumo
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Omvårdnad. Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Parenthood in transition – challenges and opportunities encountered in the host country2016Konferensbidrag (Refereegranskat)
  • 263.
    Osman, Fatumo
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Omvårdnad. Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Parenthood in transition – Somali-born parents’ experiences of and needs for parenting support programmes2015Konferensbidrag (Refereegranskat)
  • 264.
    Osman, Fatumo
    et al.
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Omvårdnad. Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Flacking, Renée
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Omvårdnad.
    Schön, Ulla-Karin
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Socialt arbete.
    Klingberg-Allvin, Marie
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Omvårdnad.
    A support program for Somali-born parents on children's behavioral problems2017Ingår i: Pediatrics, ISSN 0031-4005, E-ISSN 1098-4275, Vol. 139, nr 3Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVES: The objectives of this study were to evaluate a culturally tailored parenting support program (Ladnaan) for Somali-born parents and to determine its effectiveness on children’s emotional and behavioral problems.

    METHODS: This randomized controlled trial included 120 Somali-born parents with children aged 11 to 16 years. The parents reported self-perceived stress in relation to parenting practices. The intervention consisted of culturally tailored societal information combined with the parenting program Connect. Parents received 12 weeks of intervention, 1 to 2 hours each week, in groups of 12 to 17 parents. Nine group leaders with a Somali background who received a standardized training program delivered the intervention. The primary outcome was a decrease in emotional and behavioral problems based on a Child Behavior Checklist. Parents were randomly allocated either to an intervention group or a wait-list control group. Covariance analyses were conducted according to intention-to-treat principles.

    RESULTS: The results showed significant improvement in the children in the intervention group for behavioral problems after a 2-month follow-up. The largest effect sizes according to Cohen’s d were in aggressive behavior (95% confidence interval [CI], 1.06 to 3.07), social problems (95% CI, 0.64 to 1.70), and externalizing problems (95% CI, 0.96 to 3.53).

    CONCLUSIONS: The large effect sizes in this study show that this 12-week culturally tailored parenting support program was associated with short-term improvements in children’s behavior. The study adds to the field of parenting interventions by demonstrating how to culturally tailor, engage, and retain parenting programs for immigrant parents.

  • 265.
    Osman, Fatumo
    et al.
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Omvårdnad. Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Flacking, Renée
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Omvårdnad.
    Schön, Ulla-Karin
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Socialt arbete.
    Klingberg-Allvin, Marie
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Omvårdnad.
    The impact of a culturally tailored parenting support for Somali-born parents’ and children’s mental health: A randomized controlled trial2017Konferensbidrag (Refereegranskat)
  • 266.
    Palmcrantz, Susanne
    et al.
    Karolinska institutet.
    Tistad, Malin
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Karolinska institutet.
    Eldh, Ann Catrine
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Omvårdnad. Karolinska institutet.
    Holmqvist, Lotta Widén
    Karolinska institutet.
    Ehrenberg, Anna
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Omvårdnad.
    Tomson, Göran
    Karolinska institutet.
    Olsson, Christina B
    Karolinska institutet; Stockholm läns landsting.
    Wallin, Lars
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Omvårdnad. Karolinska institutet.
    Assessing feasibility and acceptability of study procedures: getting ready for implementation of national stroke guidelines in out-patient health care2015Ingår i: BMC Health Services Research, ISSN 1472-6963, E-ISSN 1472-6963, Vol. 15, artikel-id 517Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Even though Swedish national guidelines for stroke care (SNGSC) have been accessible for nearly a decade access to stroke rehabilitation in out-patient health care vary considerably. In order to aid future interventions studies for implementation of SNGSC, this study assessed the feasibility and acceptability of study procedures including analysis of the context in out-patient health care settings.

    METHODS: The feasibility and acceptability of recruitment, observations and interviews with managers, staff and patients were assessed, as well as the feasibility of surveying health care records.

    RESULTS: To identify patients from the the hospitals was feasible but not from out-patient care where a need to relieve clinical staff of the recruitment process was identified. Assessing adherence to guidelines and standardized evaluations of patient outcomes through health care records was found to be feasible and suitable assessment tools to evaluate patient outcome were identified. Interviews were found to be a feasible and acceptable tool to survey the context of the health care setting.

    CONCLUSION: In this feasibility study a variety of qualitative and quantitative data collection procedures and measures were tested. The results indicate what can be used as a set of feasible and acceptable data collection procedures and suitable measures for studying implementation of stroke guidelines in an out-patient health care context.

  • 267. Palmcrantz, Susanne
    et al.
    Widen Holmqvist, Lotta
    Sommerfeld K., Disa
    Tistad, Malin
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Ytterberg, Charlotte
    von Koch, Lena
    Differences between younger and older individuals in their use of care and rehabilitation but not in self-perceived global recovery 1 year after stroke2012Ingår i: Journal of the Neurological Sciences, ISSN 0022-510X, E-ISSN 1878-5883, Vol. 321, nr 1-2, s. 29-34Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Although priorities in Swedish stroke care should be based on the ethical principles of equal care and greatest support to those in greatest need, being of working age (younger) or retired (older) might influence expectations on recovery and the provision of care and rehabilitation.

    Method: Information regarding the use of care and rehabilitation during the 1st year after stroke was retrieved from the Stockholm County Council database and the medical data was taken from the medical records. The Barthel Index was used for self-ratings of dependence pre-stroke, and the Stroke Impact Scale was used to assess self-perceived disability and a global rating of recovery at 12 months. One hundred and ninety-two individuals were included.

    Results: Results showed that the younger group received more care and rehabilitation than the older group. In the older group, comorbid conditions and pre-stroke dependence, estimated in accordance with the Barthel Index, were more common. The older group reported larger impact on self-perceived disability regarding strength, mobility, self-care and domestic life, while self-perceived global recovery did not differ between the groups.

    Conclusion: Younger individuals received more care and rehabilitation, which indicates structural inequality in the provision of health care resources. However, as no difference in self-perceived global recovery was found between the groups; the disparity in the provision of health care may also be a consequence of greatest support being given to those in greatest need. By demonstrating the necessity of involving self-rated assessments of stroke impact at different points in time and in different age groups, the results of this study add to previous knowledge of age-related differences in the provision of health care and stroke outcome. Furthermore. this suggests a way to approach evaluation of equality in the provision of health care.

  • 268.
    Pers, Liselott
    et al.
    Högskolan Dalarna, Akademin Hälsa och samhälle, Medicinsk vetenskap.
    Överbring, Annika
    Högskolan Dalarna, Akademin Hälsa och samhälle, Medicinsk vetenskap.
    Omvårdnadsåtgärder för äldre med dysfagi2007Självständigt arbete på grundnivå (kandidatexamen)Studentuppsats (Examensarbete)
    Abstract [sv]

    Syftet med föreliggande systematiska litteraturstudie var att undersöka vilka omvårdnadsåtgärder som var användbara för sjuksköterskan i arbetet med äldre som led av dysfagi. Artiklar i fulltext söktes från högskolan Dalarnas biblioteks databaser och artiklarnas vetenskapliga kvalitet granskades utifrån modifierade mallar efter Forsbergs och Wengströms (2003) samt Willmans, Stoltzs och Bahtsevanis (2006) granskningsmallar. I resultatet framkom vikten av att identifiera och kartlägga äldre som led av dysfagi. Födans konsistens visade sig vara av avgörande betydelse för god sväljning. Individuellt anpassad konsistens samt mentol, kapsaicin och svartpepparolja utgjorde stimuli för sväljningsreflexen, vilka ledde till säkrare sväljning. Munvård var en lämplig omvårdnadsåtgärd då den stimulerade sväljningsreflexen samt minskade risken för aspirationspneumoni. Sjuksköterskans insikter och åtgärder var avgörande för informationen så att den äldre fick ökad kunskap om sin egenvård. Vårdpersonalen behöver mer kunskap om användbara individuella omvårdnadsåtgärder för den äldre med dysfagi.

  • 269. Petersson, H
    et al.
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Uppsala University.
    Zethelius, B
    Risérus, U
    Serum fatty acid composition and insulin resistance are independently associated with liver fat markers in elderly men2010Ingår i: Diabetes Research and Clinical Practice, ISSN 0168-8227, E-ISSN 1872-8227, Vol. 87, nr 3, s. 379-384Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aim: To investigate the relationships of serum fatty acid (FA) composition and estimated desaturase activities with the liver fat marker alanine aminotransferase (ALT). 

    Methods: 546 Swedish elderly men of a population-based cohort participated in this cross-sectional study. FA composition was assessed in serum cholesterol esters to determine dietary fat quality (e.g. linoleic) and desaturation products (e.g. dihomo-gamma-linolenic acid). Desaturase indices, including stearoyl coenzymeA desaturase-1 (SCD-1), were calculated by FA product-to-precursor ratios. 

    Results: In linear regression analyses adjusting for lifestyle, abdominal obesity and insulin sensitivity, the dietary biomarker linoleic acid (n-6), but not n-3 FAs, was inversely related to ALT. Desaturation products including palmitoleic, oleic, gamma-linolenic and dihomo-gamma-linolenic acids, and Delta 6-desaturase and SCD-1 indices were directly related to ALT (all p < 0.05). After further adjustment for factors previously linked to fatty liver (i.e. serum lipids, adiponectin concentrations), SCD-1 index (p = 0.004) and insulin resistance (p <0.0001) were independent determinants of ALT activity, whereas waist circumference, triglycerides, non-esterified FA and adiponectin were not. 

    Conclusion: A low dietary intake of linoleic acid and elevated SCD-1 index may contribute to higher ALT activity in elderly men, even independently of obesity and insulin resistance.

  • 270. Posch, Markus
    et al.
    Schranz, Alois
    Lener, Manfred
    Senn, Werner
    Äng, Björn
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Karolinska institutet.
    Burtscher, Martin
    Ruedl, Gerhard
    Prevalence and potential risk factors of flight-related neck, shoulder and low back pain among helicopter pilots and crewmembers: a questionnaire-based study2019Ingår i: BMC Musculoskeletal Disorders, ISSN 1471-2474, E-ISSN 1471-2474, Vol. 20, nr 1, artikel-id 44Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Flight-related neck, shoulder and low back pain are the most common musculoskeletal disorders among helicopter pilots and their crewmembers, thus becoming a growing concern. Information on the combined prevalence of these types of pain and related risks are scarce. The aim of this study was therefore to estimate pain prevalence and to evaluate potential risk factors for neck pain among helicopter pilots and crewmembers within the armed forces, the airborne police and airborne rescue organizations in Austria.

    METHODS: Among a cohort of 104 helicopter pilots and 117 crewmembers (69.8% compliance), demographics, flying experience, use of Night Vision Goggles (NVG), helicopter type flown, prevalence and intensity of musculoskeletal symptoms (pain was defined as any reported pain experience, ache or discomfort) were collected by an online-based questionnaire.

    RESULTS: For helicopter pilots the 12-month prevalence of neck pain was 67.3%, followed by low back (48.1%) and shoulder pain (43.3%). Among crewmembers, the 12-month pain prevalence were 45.3, 36.8 and 30.8% among the neck, lower back and shoulder, respectively. During this period, 41.8% of these helicopter pilots had experienced 8-30 pain days in the areas of neck (45.7%), shoulder (37.8%) and lower back (42.0%) whereas 47.8% of crewmembers self-reported 1-7 days of neck (54.7%), low back (44.2%) and shoulder (44.4%) pain in the previous year. The 3-month prevalence of neck pain was 64.4% followed by low back (42.3%) and shoulder pain (38.5%) for helicopter pilots. Among crewmembers, 41.9% suffered from neck, 29.9% from low back and 29.1% from shoulder pain the previous 3 months. Multivariate regression analysis revealed NVG use (OR 1.9, 95% CI, 1.06-3.50, p = 0.032), shoulder pain (OR 4.9, 95% CI, 2.48-9.55, p < 0.001) and low back pain (OR 2.3, 95% CI, 1.21-4.31, p = 0.011) to be significantly associated with neck pain.

    CONCLUSIONS: The 12- and 3-month prevalence of neck, shoulder and low back is considerably high among both, helicopter pilots and crewmembers confirming the existence of this growing concern. The use of NVG devices, shoulder and low back pain in the previous 12 months represent independent risk factors for neck pain. These findings highlight the need for longitudinal studies.

  • 271. Roos, Vendela
    et al.
    Elmståhl, Sölve
    Ingelsson, Erik
    Sundström, Johan
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Uppsala universitet.
    Lind, Lars
    Alterations in multiple lifestyle factors in subjects with the metabolic syndrome independently of obesity2017Ingår i: Metabolic Syndrome and Related Disorders, ISSN 1540-4196, E-ISSN 1557-8518, Vol. 15, nr 3, s. 118-123Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Many lifestyle factors have been associated with the metabolic syndrome (MetS). However, most of these studies have not considered the potential impact of obesity and have often only investigated one lifestyle factor at the time. We aimed to investigate the interplay between body mass index (BMI) and MetS with respect to multiple lifestyle factors.

    METHODS: BMI and MetS [National Cholesterol Education Program (NCEP)/Adult Treatment Panel III criteria] were assessed in a sample of 18,880 subjects aged 45-75 years from the population-based EpiHealth study. Participants were categorized into six groups according to BMI category (normal weight/BMI <25 kg/m(2), overweight/BMI 25-30 kg/m(2), and obesity/BMI >30 kg/m(2)) and MetS status (+/-, NCEP criteria). A wide range of lifestyle factors related to physical activity, smoking, alcohol, sleep quality, working conditions, quality of life and stress, and eating patterns were assessed using a questionnaire.

    RESULTS: Prevalent MetS (23% in the sample) was associated with less physical activity (P < 0.0001), more TV watching (P < 0.0001), more years of smoking (P < 0.0001), lower education level (P = 0.007), and experiencing a poor general quality of life (P < 0.0001). These lifestyle factors were all associated with MetS, independently of each other and independently of BMI. Similar results were generated when number of MetS components and presence/absence of individual MetS components were used as outcomes.

    CONCLUSIONS: This cross-sectional study identified alterations in a number of lifestyle factors associated with MetS independently of each other and independently of BMI. Future longitudinal studies are needed to assess causal and temporal relationships between lifestyle factors and MetS development.

  • 272. Roos, Vendela
    et al.
    Elmståhl, Sölve
    Ingelsson, Erik
    Sundström, Johan
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Uppsala universitet.
    Lind, Lars
    Metabolic syndrome development during aging with special reference to obesity without the metabolic syndrome2017Ingår i: Metabolic Syndrome and Related Disorders, ISSN 1540-4196, E-ISSN 1557-8518, Vol. 15, nr 1, s. 36-43Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Obesity and its associated metabolic complications continue to increase worldwide. We investigated the development of metabolic syndrome (MetS) during aging in relation to body mass index (BMI) and exercise habits. We assigned special emphasis to the metabolic stability in individuals with obesity, but without MetS, a condition often referred to as metabolically healthy obesity.

    MATERIALS AND METHODS: Cross-sectional analysis was carried out in a sample of 19,129 men and women aged 45-75 years from the EpiHealth study. In addition, longitudinal analyses were carried out in the ULSAM study (2322 men at baseline followed from age 50 to age 77) and in the PIVUS study (1016 men and women at baseline followed from age 70 to age 80). Participants were categorized into six groups according to BMI category (normal weight/BMI <25 kg/m(2), overweight/BMI 25-30 kg/m(2), and obesity/BMI >30 kg/m(2)) and MetS status (+/-, National Cholesterol Education Program criteria).

    RESULTS: MetS prevalence and number of MetS components increased with age in all three samples. The PIVUS study showed that high baseline BMI, low baseline physical activity, and increasing BMI during follow-up were related to increasing MetS prevalence and increasing numbers of MetS components during follow-up. One-third to half of individuals initially belonging to the obesity without MetS category acquired MetS during aging.

    CONCLUSIONS: MetS prevalence increased during aging, especially in individuals with high BMI, low level of physical activity, and weight gain. Obesity without MetS was not a stable condition over time as many of those individuals gained metabolic disturbances during aging.

  • 273. Roth, Gregory
    et al.
    Abate, Degu
    Abate, Kalkidan Hassenn
    Abay, Solomon
    Abbasi, Nooshin
    Abbastabar, Heyadat
    Abd-Allah, Load
    Abdela, Jemal
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Karolinska institutet.
    Murray, Christopher J. L
    Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980-2017: a systematic analysis for the Global Burden of Disease Study 20172018Ingår i: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 392, nr 10159, s. 1736-1788Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background Global development goals increasingly rely on country-specific estimates for benchmarking a nation's progress. To meet this need, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016 estimated global, regional, national, and, for selected locations, subnational cause-specific mortality beginning in the year 1980. Here we report an update to that study, making use of newly available data and improved methods. GBD 2017 provides a comprehensive assessment of cause-specific mortality for 282 causes in 195 countries and territories from 1980 to 2017. 

    Methods The causes of death database is composed of vital registration (VR), verbal autopsy (VA), registry, survey, police, and surveillance data. GBD 2017 added ten VA studies, 127 country-years of VR data, 502 cancer-registry country-years, and an additional surveillance country-year. Expansions of the GBD cause of death hierarchy resulted in 18 additional causes estimated for GBD 2017. Newly available data led to subnational estimates for five additional countries Ethiopia, Iran, New Zealand, Norway, and Russia. Deaths assigned International Classification of Diseases (ICD) codes for non-specific, implausible, or intermediate causes of death were reassigned to underlying causes by redistribution algorithms that were incorporated into uncertainty estimation. We used statistical modelling tools developed for GBD, including the Cause of Death Ensemble model (CODErn), to generate cause fractions and cause specific death rates for each location, year, age, and sex. Instead of using UN estimates as in previous versions, GBD 2017 independently estimated population size and fertility rate for all locations. Years of life lost (YLLs) were then calculated as the sum of each death multiplied by the standard life expectancy at each age. All rates reported here are age-standardised. 

    Findings At the broadest grouping of causes of death (Level 1), non-communicable diseases (NC Ds) comprised the greatest fraction of deaths, contributing to 73.4% (95% uncertainty interval [UI] 72.5-74.1) of total deaths in 2017, while communicable, maternal, neonatal, and nutritional (CMNN) causes accounted for 186% (17.9-19.6), and injuries 8.0% (7.7-8.2). Total numbers of deaths from NCD causes increased from 2007 to 2017 by 22.7% (21.5-23.9), representing an additional 7.61 million (7. 20-8.01) deaths estimated in 2017 versus 2007. The death rate from NCDs decreased globally by 7.9% (7.08.8). The number of deaths for CMNN causes decreased by 222% (20.0-24.0) and the death rate by 31.8% (30.1-33.3). Total deaths from injuries increased by 2.3% (0-5-4-0) between 2007 and 2017, and the death rate from injuries decreased by 13.7% (12.2-15.1) to 57.9 deaths (55.9-59.2) per 100 000 in 2017. Deaths from substance use disorders also increased, rising from 284 000 deaths (268 000-289 000) globally in 2007 to 352 000 (334 000-363 000) in 2017. Between 2007 and 2017, total deaths from conflict and terrorism increased by 118.0% (88.8-148.6). A greater reduction in total deaths and death rates was observed for some CMNN causes among children younger than 5 years than for older adults, such as a 36.4% (32.2-40.6) reduction in deaths from lower respiratory infections for children younger than 5 years compared with a 33.6% (31.2-36.1) increase in adults older than 70 years. Globally, the number of deaths was greater for men than for women at most ages in 2017, except at ages older than 85 years. Trends in global YLLs reflect an epidemiological transition, with decreases in total YLLs from enteric infections, respirator}, infections and tuberculosis, and maternal and neonatal disorders between 1990 and 2017; these were generally greater in magnitude at the lowest levels of the Socio-demographic Index (SDI). At the same time, there were large increases in YLLs from neoplasms and cardiovascular diseases. YLL rates decreased across the five leading Level 2 causes in all SDI quintiles. The leading causes of YLLs in 1990 neonatal disorders, lower respiratory infections, and diarrhoeal diseases were ranked second, fourth, and fifth, in 2017. Meanwhile, estimated YLLs increased for ischaemic heart disease (ranked first in 2017) and stroke (ranked third), even though YLL rates decreased. Population growth contributed to increased total deaths across the 20 leading Level 2 causes of mortality between 2007 and 2017. Decreases in the cause-specific mortality rate reduced the effect of population growth for all but three causes: substance use disorders, neurological disorders, and skin and subcutaneous diseases. 

    Interpretation Improvements in global health have been unevenly distributed among populations. Deaths due to injuries, substance use disorders, armed conflict and terrorism, neoplasms, and cardiovascular disease are expanding threats to global health. For causes of death such as lower respiratory and enteric infections, more rapid progress occurred for children than for the oldest adults, and there is continuing disparity in mortality rates by sex across age groups. Reductions in the death rate of some common diseases are themselves slowing or have ceased, primarily for NCDs, and the death rate for selected causes has increased in the past decade.

  • 274.
    Rudholm Feldreich, Tobias
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Uppsala universitet.
    Urinary osteopontin predicts incident chronic kidney disease, while plasma osteopontin predicts cardiovascular death in elderly men2016Konferensbidrag (Refereegranskat)
    Abstract [en]

    Background and objectives The matricellular protein osteopontin is involved in the pathogenesis of both kidney and cardiovascular disease. However, whether circulating and urinary osteopontin levels are associated with the risk of these diseases is less studied.

    Design, setting, participants and measurements A community-based cohort of elderly (Uppsala Longitudinal Study of Adult Men [ULSAM; n=741; mean age: 77 years]) was used to study the associations between plasma and urinary osteopontin, incident chronic kidney disease, and the risk of cardiovascular death during a median of 8 years of follow-up.

    Results There was no significant cross-sectional correlation between plasma and urinary osteopontin (Spearman rho=0.07, p=0.13). Higher urinary, but not plasma osteopontin, was associated with incident chronic kidney disease in multivariable models adjusted for age, cardiovascular risk factors, baseline glomerular filtration rate (GFR), urinary albumin/creatinine ratio, and inflammatory markers interleukin 6 and high sensitivity C-reactive protein (Odds ratio for 1-standard deviation (SD) of urinary osteopontin, 1.42, 95% CI (1.00-2.02), p=0.048). Conversely, plasma osteopontin, but not urinary osteopontin, was independently associated with cardiovascular death (multivariable hazard ratio per SD increase, 1.35, 95% CI (1.14-1.58), p<0.001, and 1.00, 95% CI (0.79-1.26), p=0.99, respectively). The addition of plasma osteopontin to a model with established cardiovascular risk factors significantly increased the C-statistics for the prediction of cardiovascular death (p<0.002).

    Conclusions Higher urinary osteopontin specifically predicts incident chronic kidney disease while plasma osteopontin specifically predicts cardiovascular death. Our data put forward osteopontin as an important factor in the detrimental interplay between the kidney and the cardiovascular system. The clinical implications, and why plasma and urinary osteopontin mirror different pathologies, remains to be established.

  • 275.
    Rudholm Feldreich, Tobias
    et al.
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Uppsala universitet.
    Carlsson, Axel C
    Risérus, Ulf
    Larsson, Anders
    Lind, Lars
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Uppsala universitet.
    The association between serum cathepsin L and mortality in older adults2016Ingår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 254, s. 109-116Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND AND AIMS: Research suggests that the protease cathepsin L is causally involved in atherosclerosis. However, data on cathepsin L as a risk marker are lacking. Therefore, we investigated associations between circulating cathepsin L and cardiovascular mortality.

    METHODS: Two independent community-based cohorts were used: Uppsala Longitudinal Study of Adult Men (ULSAM); n = 776; mean age 77 years; baseline 1997-2001; 185 cardiovascular deaths during 9.7 years follow-up, and Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS); n = 993; 50% women; mean age 70 years; baseline 2001-2004; 42 cardiovascular deaths during 10.0 years follow-up.

    RESULTS: Higher serum cathepsin L was associated with an increased risk for cardiovascular mortality in age- and sex-adjusted models in both cohorts (ULSAM: hazard ratio (HR) for 1-standard deviation (SD) increase, 1.17 [95% CI, 1.01-1.34], p = 0.032 PIVUS: HR 1.35 [95% CI, 1.07-1.72], p = 0.013). When merging the cohorts, these associations were independent of inflammatory markers and cardiovascular risk factors, but non-significant adjusting for kidney function. Individuals with a combination of elevated cathepsin L and increased inflammation, kidney dysfunction, or prevalent cardiovascular disease had a markedly increased risk, while no increased risk was associated with elevated cathepsin L, in the absence of these disease states.

    CONCLUSIONS: An association between higher serum cathepsin L and increased risk of cardiovascular mortality was found in two independent cohorts. Impaired kidney function appears to be an important moderator or mediator of these associations. Further studies are needed to delineate the underlying mechanisms and to evaluate whether the measurement of cathepsin L might have clinical utility.

  • 276.
    Rudholm Feldreich, Tobias
    et al.
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Karolinska Institutet; Uppsala universitet.
    Nowak, Christoph
    Fall, Tove
    Carlsson, Axel C
    Carrero, Juan-Jesus
    Ripsweden, Jonas
    Qureshi, Abdul Rashid
    Heimbürger, Olof
    Barany, Peter
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Karolinska Institutet.
    Circulating proteins as predictors of cardiovascular mortality in end-stage renal disease2018Ingår i: JN. Journal of Nephrology (Milano. 1992), ISSN 1121-8428, E-ISSN 1724-6059, Vol. 32, nr 1, s. 111-119Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    INTRODUCTION: Proteomic profiling of end-stage renal disease (ESRD) patients could lead to improved risk prediction and novel insights into cardiovascular disease mechanisms. Plasma levels of 92 cardiovascular disease-associated proteins were assessed by proximity extension assay (Proseek Multiplex CVD-1, Olink Bioscience, Uppsala, Sweden) in a discovery cohort of dialysis patients, the Mapping of Inflammatory Markers in Chronic Kidney disease cohort [MIMICK; n = 183, 55% women, mean age 63 years, 46 cardiovascular deaths during follow-up (mean 43 months)]. Significant results were replicated in the incident and prevalent hemodialysis arm of the Salford Kidney Study [SKS dialysis study, n = 186, 73% women, mean age 62 years, 45 cardiovascular deaths during follow-up (mean 12 months)], and in the CKD5-LD-RTxcohort with assessments of coronary artery calcium (CAC)-score by cardiac computed tomography (n = 89, 37% women, mean age 46 years).

    RESULTS: In age and sex-adjusted Cox regression in MIMICK, 11 plasma proteins were nominally associated with cardiovascular mortality (in order of significance: Kidney injury molecule-1 (KIM-1), Matrix metalloproteinase-7, Tumour necrosis factor receptor 2, Interleukin-6, Matrix metalloproteinase-1, Brain-natriuretic peptide, ST2 protein, Hepatocyte growth factor, TNF-related apoptosis inducing ligand receptor-2, Spondin-1, and Fibroblast growth factor 25). Only plasma KIM-1 was associated with cardiovascular mortality after correction for multiple testing, but also after adjustment for dialysis vintage, cardiovascular risk factors and inflammation (hazard ratio) per standard deviation (SD) increase 1.84, 95% CI 1.26-2.69, p = 0.002. Addition of KIM-1, or nine of the most informative proteins to an established risk-score (modified AROii CVM-score) improved discrimination of cardiovascular mortality risk from C = 0.777 to C = 0.799 and C = 0.823, respectively. In the SKS dialysis study, KIM-1 predicted cardiovascular mortality in age and sex adjusted models (hazard ratio per SD increase 1.45, 95% CI 1.03-2.05, p = 0.034) and higher KIM-1 was associated with higher CACscores in the CKD5-LD-RTx-cohort.

    CONCLUSIONS: Our proteomics approach identified plasma KIM-1 as a risk marker for cardiovascular mortality and coronary artery calcification in three independent ESRD-cohorts. The improved risk prediction for cardiovascular mortality by plasma proteomics merit further studies.

  • 277.
    Ruge, T
    et al.
    Department of Surgery, Umeå University, Umeå, Sweden.
    Södergren, A
    Department of Public Health and Clinical Medicine/Rheumatology, Umeå University Hospital, Umeå, Sweden.
    Wållberg-Jonsson, S
    e/Rheumatology, Umeå University Hospital, Umeå, Sweden.
    Larsson, A
    Department of Medical Sciences, Uppsala University Hospital, 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.
    Circulating plasma levels of cathepsin S and L are not associated with disease severity in patients with rheumatoid arthritis2014Ingår i: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 43, nr 2, s. 371-373Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Rheumatoid arthritis (RA) is characterized by chronic synovitis and articular cartilage destruction. Increased activities of cathepsin S and cathepsin L, two potent cysteine proteases, are thought to play a role in the pathogenesis of the irreversible articular cartilage destruction. Nevertheless, data regarding the potential importance of the cathepsins as circulating biomarkers in RA patients are limited.

    Method: Subjects enrolled in this study are part of a larger study where patients from the three northern counties of Sweden diagnosed with early RA are followed in an ongoing prospective study. In total, 71 patients were included, along with 44 age- and sex-matched control subjects. Plasma levels of cathepsin S and L were analysed. Disease severity was assessed using the 28-joint count Disease Activity Score (DAS28).

    Results: Plasma levels of cathepsin S and L were significantly increased in patients with RA compared to healthy controls (p < 0.05 for both). However, in the patients with RA, no association between the cathepsins and the severity of the disease, as characterized by DAS28, was observed (p > 0.51).

    Conclusions: Although circulating levels of cathepsin S and L were significantly increased in patients with recently diagnosed RA, our data do not support the notion that circulating levels of cathepsins are relevant biomarkers for disease severity.

  • 278. Ruge, Toralph
    et al.
    Carlsson, Axel C.
    Ingelsson, Erik
    Risérus, Ulf
    Sundström, Johan
    Larsson, Anders
    Lind, Lars
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Karolinska institutet.
    Circulating endostatin and the incidence of heart failure2018Ingår i: Scandinavian Cardiovascular Journal, ISSN 1401-7431, E-ISSN 1651-2006, Vol. 52, nr 5, s. 244-249Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE:

    Circulating levels of endostatin are elevated in many underlying conditions leading to heart failure such as hypertension, diabetes, chronic kidney disease and ischemic heart disease. Yet, the association between endostatin and the incidence of heart failure has not been reported previously in the community.

    DESIGN:

    We investigated the longitudinal association between serum endostatin levels and incident heart failure in two community-based cohorts of elderly: Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS, n = 966; mean age 70 years, 51% women, 81 events, mean follow-up 10 years) and Uppsala Longitudinal Study of Adult Men (ULSAM, n = 747 men; mean age 78 years, 98 heart failure events, mean follow-up 8 years). We also investigated the cross-sectional association between endostatin and echocardiographic left ventricular systolic function and diastolic function (ejection fraction and E/A-ratio, respectively).

    RESULTS:

    Higher serum endostatin was associated with an increased risk for heart failure in both cohorts after adjustment for established heart failure risk factors, glomerular filtration rate and N-terminal pro-brain natriuretic peptide (NT-proBNP) (PIVUS: multivariable hazard ratio (HR) per 1-standard deviation (SD) increase, HR 1.46 (95%CI, 1.17-1.82, p < .001); ULSAM: HR 1.29 (95%CI, 1.00-1.68, p < .05). In cross-sectional analyses at baseline, higher endostatin was significantly associated with both worsened left ventricular systolic and diastolic function in both cohorts. Conclusion Higher serum endostatin was associated with left ventricular dysfunction and an increased heart failure risk in two community-based cohorts of elderly. Our findings encourage further experimental studies that investigate the role of endostatin in the development of heart failure.

  • 279. Ruge, Toralph
    et al.
    Carlsson, Axel C
    Jansson, Jan-Håkan
    Söderberg, Stefan
    Larsson, Anders
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Karolinska institutet.
    The association between circulating endostatin levels and incident myocardial infarction2018Ingår i: Scandinavian Cardiovascular Journal, ISSN 1401-7431, E-ISSN 1651-2006, Vol. 52, nr 6, s. 315-319Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: Increased levels of circulating endostatin have been observed in patients with prevalent ischemic heart disease. However, the association between circulating endostatin, and incident myocardial infarction (MI) is less studied. Our main aim was to study the association between circulating endostatin and incident MI in the community adjusted for established cardiovascular risk factors in men and women.

    DESIGN: Circulating endostatin was measured in a nested case control study based on three large community-based Swedish cohorts, including 533 MI cases, and 1003 age-, sex- and cohort-matched controls. Odds ratios (OR) with 95% confidence intervals (CI) were calculated with adjustments for established cardiovascular risk factors.

    RESULTS: Higher endostatin was associated with a higher incidence of MI independently of established cardiovascular risk factors (OR 1.19, 95 % CI 1.03-1.37, p = 0.02), but this association was abolished after additional adjustment for C-reactive protein. Sex-stratified analyses suggest that the association was substantially stronger in women as compared to men Conclusions: In our community based sample, higher endostatin predicted incident myocardial infarction predominantly in women but not independently of CRP. Thus, our findings do not support a broad utility of endostatin measurements for the prediction of incident myocardial infarction in clinical practice.

  • 280. Ruge, Toralph
    et al.
    Carlsson, Axel C
    Larsson, Anders
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Karolinska institutet.
    Endostatin: a promising biomarker in the cardiovascular continuum?2017Ingår i: Biomarkers in Medicine, ISSN 1752-0363, E-ISSN 1752-0371, Vol. 11, nr 10, s. 905-916Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The current review article aims to provide an up-to-date summary of previous studies in humans that have reported the association between circulating endostatin levels and different cardiovascular phenotypes. We also aim to provide suggestions for future directions of future research evaluating endostatin as a clinically relevant cardiovascular biomarker. With a few exceptions, higher circulating levels of endostatin seem to reflect vascular and myocardial damage, and a worsened prognosis for cardiovascular events or mortality in individuals with hypertension, diabetes, kidney disease, cardiovascular disease, as well as in the general population. Circulating endostatin seems to be a promising biomarker for cardiovascular pathology, but there is not enough evidence to date to support the use of endostatin measurements in clinical practice.

  • 281. Ruge, Toralph
    et al.
    Carlsson, Axel C
    Larsson, Tobias E
    Carrero, Juan-Jesús
    Larsson, Anders
    Lind, Lars
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Endostatin level is associated with kidney injury in the elderly: findings from two community-based cohorts2014Ingår i: American Journal of Nephrology, ISSN 0250-8095, E-ISSN 1421-9670, Vol. 40, nr 5, s. 417-424Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: We aimed to investigate the associations between circulating endostatin and the different aspects of renal dysfunction, namely, estimated (cystatin C) glomerular filtration rate (GFR) and urine albumin-creatinine ratio (ACR).

    METHODS: Two independent longitudinal community-based cohorts of elderly. ULSAM, n = 786 men; age 78 years; median GFR 74 ml/min/1.73 m(2); median ACR 0.80 mg/mmol); and PIVUS, n = 815; age 75 years; 51% women; median GFR; 67 ml/min/1.73 m(2); median ACR 1.39 mg/mmol. Cross-sectional associations between the endostatin levels and GFR as well as ACR, and longitudinal association between endostatin at baseline and incident CKD (defined as GFR <60 ml/min/1.73 m(2)) were assessed.

    RESULTS: In cross-sectional regression analyses adjusting for age, gender, inflammation, and cardiovascular risk factors, serum endostatin was negatively associated with GFR (ULSAM: B-coefficient per SD increase -0.51, 95% CI (-0.57, -0.45), p < 0.001; PIVUS -0.47, 95% CI (-0.54, -0.41), p < 0.001) and positively associated with ACR (ULSAM: B-coefficient per SD increase 0.24, 95% CI (0.15, 0.32), p < 0.001; PIVUS 0.13, 95% CI (0.06-0.20), p < 0.001) in both cohorts. Moreover, in longitudinal multivariable analyses, higher endostatin levels were associated with increased risk for incident CKD defined as GFR <60 ml/min/1.73 m(2) at re-investigations in both ULSAM (odds ratio per SD increase of endostatin 1.39 (95% CI 1.01-1.90) and PIVUS 1.68 (95% CI 1.36-2.07)).

    CONCLUSIONS: Higher circulating endostatin is associated with lower GFR and higher albuminuria and independently predicts incident CKD in elderly subjects. Further studies are warranted to investigate the underlying mechanisms linking endostatin to kidney pathology, and to evaluate the clinical relevance of our findings. © 2014 S. Karger AG, Basel.

  • 282. Rydell, Andreas
    et al.
    Janson, Christer
    Lisspers, Karin
    Ställberg, Björn
    Nowak, Christoph
    Carlsson, Axel C.
    Feldreich, Tobias
    Iggman, David
    Lind, Lars
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Karolinska institutet.
    Endothelial dysfunction is associated with impaired lung function in two independent community cohorts2018Ingår i: Respiratory Medicine, ISSN 0954-6111, E-ISSN 1532-3064, Vol. 143, s. 123-128Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background

    Prior studies investigating the association between endothelial dysfunction and impaired lung function have been small and inconsistent. The primary aim was to investigate the association between endothelial function and lung function in two community-based cohorts.

    Methods

    We used a discovery/replication approach to study the association between endothelial function and lung function in the Prospective investigation of Obesity, Energy and Metabolism (POEM, discovery cohort, n = 490, mean age 50.3 ± 0.2 years) and the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS, replication cohort, n = 892, mean age 70.2 ± 0.15 years). Spirometry and three different measures of endothelial function were performed including both the invasive forearm technique (endothelium-dependent and endothelium-independent vasodilation [EDV and EIDV, respectively] and noninvasive flow mediated dilation [FMD]).

    Results

    An age and sex adjusted association between lower EDV and lower FEV1 was found in POEM and replicated in PIVUS. After merging the two cohorts, 1 standard deviation decrease in EDV was associated with 1.57% lower FEV1 after additional adjustment for smoking status, body mass index, exercise level, and C-reactive protein (95% confidence intervals 0.63–2.51, p = 0.001). The association was slightly lower albeit still statistically significant after excluding participants without cardiovascular disease and chronic respiratory disease and appeared stronger among previous/current smokers vs. non-smokers and in men vs. women (p for interaction = 0.2 and 0.02 respectively).

    Conclusions

    Our findings suggest that even individuals with sub-clinical impairments of lung function in the community have concomitant endothelial dysfunction.

  • 283. Röijezon, Ulrik
    et al.
    Løvoll, Grunde
    Henriksson, Anders
    Tonkonogi, Michail
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Lehto, Niklas
    An initial study on the coordination of rod and line hauling movements in distance fly casting2017Ingår i: Annals of Applied Sport Science, ISSN 2322-4479, Vol. 5, nr 2, s. 61-72Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background. The double haul is a unique feature of single-handed fly casting and is used in both fly fishing and fly casting competition. The movement behaviour during the double haul has not been investigated in previous research.

    Objectives. Describe the coordination of the rod and line hauling movements during distance fly casting.

    Methods. Elite fly casters performed distance casting with four different fly rod and fly line set-ups used in fly fishing and fly casting competition. Rod and hauling movements were measured with a 3D motion analysis system.

    Results. The rod and line hauling movements were coordinated in an order whereby peak translational speed of the rod occurs prior to the peak speed of the angular rotation of the rod, and the peak speed of the angular rotation of the rod occurs prior to the peak speed of the line haul. This was consistent for all cast sequences, i.e., the back and forward false casts and the delivery cast, and for all four equipment set-ups, i.e., a shooting-head line cast with a relatively stiff fly rod and a long-belly line cast with three different fly rods with different stiffness and action curves. Results also showed differences in movement coordination between cast sequences and rod and line set-ups.

    Conclusion. Among elite casters, single-handed fly casting with double haul is coordinated in an order of events whereby the peak speed occurs first for the translation of the rod, then for the rotation of the rod and finally for the line haul.

  • 284.
    Römsing, Susanne
    et al.
    Högskolan Dalarna, Akademin Industri och samhälle, Kemiteknik.
    Bökman, Fredrik
    Bergqvist, Yngve
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Determination of melatonin in saliva using solid-phase extraction, high-performance liquid chromatography and fluorescence detection2006Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 66, nr 3, s. 181-190Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A sensitive bioanalytical method for the determination of melatonin in saliva by solid-phase extraction (SPE), high-performance liquid chromatography (HPLC) and fluorescence detection has been developed and validated. Saliva was collected with a Salivette((R)) sampling device (Sarstedt) and a mixed-mode SPE column was used for the extraction of melatonin and internal standard (N-acetyl-6-methoxytryptamine) from the saliva. Chromatographic separation was performed using a HyPurity C18 LC column (150x2.1 mm) with mobile phase acetonitrile-ammonium hydrogen carbonate buffer, 0.015 M, pH 6.8 (23:77, v/v). Excitation and emission wavelengths were set to 285 nm and 345 nm, respectively. The within-day precision for the method at 50 pmol/L was 7.9% and the between-day precision was 10.5%. The limit of quantification was 50 pmol/L.

  • 285.
    Römsing, Susanne
    et al.
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Kemi.
    Lindegardh, Niklas
    Bergqvist, Yngve
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Determination of tafenoquine in dried blood spots and plasma using LC and fluorescence detection2011Ingår i: Bioanalysis, ISSN 1757-6180, E-ISSN 1757-6199, Vol. 3, nr 16, s. 1847-1853Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The growing problem of parasites developing resistance to the traditional antimalarial drugs makes the development of new effective and safe drugs crucial. Tafenoquine is a new promising antimalarial drug for prophylaxis and treatment.

    Results: A bioanalytical method for the determination of tafenoquine in 100 mu l of capillary blood applied onto sampling paper and in 100 mu l of plasma has been developed and validated. The Whatman 31 ET Chr paper was treated with 0.6 mol/l tartaric acid to improve the extraction recovery and solid-phase extraction was used for cleanup procedure of the blood samples. Plasma samples were precipitated with methanol. Tafenoquine and internal standard were separated on a Zorbax SB-CN column by reversed-phase LC and detected with fluorescence detection at 262 and 470 nm. The within- and between-day variations were below 10 and 14%, respectively, over the range 50-200 nmol/l for capillary blood on sampling paper and below 6 and 10% for plasma samples. The LLOQ of the method was 50 nmol/l.

    Conclusion: The developed method has adequate sensitivity and is highly suitable for clinical studies in dried blood spots and plasma.

  • 286. Sahlin, K
    et al.
    Sallstedt, E-K
    Bishop, D
    Tonkonogi, Michail
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Turning down lipid oxidation during heavy exercise--what is the mechanism?2008Ingår i: Journal of Physiology and Pharmacology, ISSN 0867-5910, E-ISSN 1899-1505, Vol. 59, nr 4, s. 19-30Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A high potential for lipid oxidation is a sign of metabolic fitness and is important not only for exercise performance but also for health promotion. Despite considerable progress during recent years, our understanding of how lipid oxidation is controlled remains unclear. The rate of lipid oxidation reaches a peak at 50-60% of (V) over dotO(2) (max) after which the contribution of lipids decreases both in relative and absolute terms. In the high-intensity domain (> 60% (V) over dotO(2 max)), there is a pronounced decrease in energy state, which will stimulate the glycolytic rate in excess of the substrate requirements of mitochondrial oxidative processes. Accumulation of glycolytic products will impair lipid oxidation through an interaction with the carnitine-mediated transfer of FA into mitochondria. Another potential site of control is Acyl-CoA synthetase (ACS), which is the initial step in FA catabolism. The activity of ACS may be under control of CoASH and energy state. There is evidence that additional control points exist beyond mitochondrial influx of fatty acids. The electron transport chain (ETC) with associated feed-back control by redox state is one suggested candidate. In this review it is suggested that the control of FA oxidation during heavy exercise is distributed between ACS, CPT1, and ETC.

  • 287. Sahlin, K
    et al.
    Shabalina, I
    Mattsson, M
    Bakkman, L
    Fernström, M
    Rozhdestvenskaya, Z
    Enqvist, J
    Nedergaard, J
    Ekblom, B
    Tonkonogi, Michail
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Ultraendurance exercise increases the production of reactive oxygen species in isolated mitochondria from human skeletal muscle2010Ingår i: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 108, nr 4, s. 780-787Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Exercise-induced oxidative stress is important for the muscular adaptation to training but may also cause muscle damage. We hypothesized that prolonged exercise would increase mitochondrial production of reactive oxygen species (ROS) measured in vitro and that this correlates with oxidative damage. Eight male athletes (24–32 yr) performed ultraendurance exercise (kayaking/running/cycling) with an average work intensity of 55% V?O2peak for 24 h. Muscle biopsies were taken from vastus lateralis before exercise, immediately after exercise, and after 28 h of recovery. The production of H2O2 was measured fluorometrically in isolated mitochondria with the Amplex red and peroxidase system. Succinate-supported mitochondrial H2O2 production was significantly increased after exercise (73% higher, P = 0.025) but restored to the initial level at recovery. Plasma level of free fatty acids (FFA) increased fourfold and exceeded 1.2 mmol/l during the last 6 h of exercise. Plasma FFA at the end of exercise was significantly correlated to mitochondrial ROS production (r = 0.74, P < 0.05). Mitochondrial content of 4-hydroxy-nonenal-adducts (a marker of oxidative damage) was increased only after recovery and was not correlated with mitochondrial ROS production. Total thiol group level and glutathione peroxidase activity were elevated after recovery. In conclusion, ultraendurance exercise increases ROS production in isolated mitochondria, but this is reversed after 28 h recovery. Mitochondrial ROS production was not correlated with oxidative damage of mitochondrial proteins, which was increased at recovery but not immediately after exercise.

  • 288. Sahlin, Kent
    et al.
    Fernström, Maria
    Tonkonogi, Michail
    Högskolan Dalarna, Akademin Hälsa och samhälle, Medicinsk vetenskap.
    No evidence of an intracellular lactate shuttle in rat skeletal muscle2002Ingår i: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 541, nr 2, s. 569-574Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The concerted view is that cytosolic pyruvate is transferred into mitochondria and after oxidative decarboxylation further metabolized in the tricarboxylic acid cycle. Recently this view has been challenged. Based on experimental evidence from rat skeletal muscle it has been concluded that mitochondria predominantly oxidize lactate in vivo and that this constitutes part of an 'intracellular lactate shuttle'. This view appears to be gaining acceptance in the scientific community and due to its conceptual importance, confirmation by independent experiments is required. We have repeated the experiments in mitochondria isolated from rat soleus muscle. Contrary to the previously published findings we cannot find any mitochondrial respiration with lactate. Analysis of lactate dehydrogenase (LDH) by spectrophotometry demonstrated that the activity in the mitochondrial fraction was only 0.7 % of total activity. However, even when external LDH was added to mitochondria, there were no signs of respiration with lactate. In the presence of conditions where lactate is converted to pyruvate (external additions of both LDH and NAD+), mitochondrial oxygen consumption increased. Furthermore, we provide theoretical evidence that direct mitochondrial lactate oxidation is energetically unlikely. Based on the present data we conclude that direct mitochondrial lactate oxidation does not occur in skeletal muscle. The presence of an 'intracellular lactate shuttle' can therefore be questioned.

  • 289. Sahlin, Kent
    et al.
    Nielsen, J.S.
    Mogensen, M
    Tonkonogi, Michail
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Repeated static contractions increase mitochondrial vulnerability toward oxidative stress in human skeletal muscle.2006Ingår i: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 101, nr 3, s. 833-839Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Repeated static contractions (RSC) induce large fluctuations in tissue oxygen tension and increase the generation of reactive oxygen species (ROS). This study investigated the effect of RSC on muscle contractility, mitochondrial respiratory function, and in vitro sarcoplasmic reticulum (SR) Ca2+ kinetics in human muscle. Ten male subjects performed five bouts of static knee extension with 10-min rest in between. Each bout of RSC (target torque 66% of maximal voluntary contraction torque) was maintained to fatigue. Muscle biopsies were taken preexercise and 0.3 and 24 h postexercise from vastus lateralis. Mitochondria were isolated and respiratory function measured after incubation with H2O2 (HPX) or control medium (Con). Mitochondrial function was not affected by RSC during Con. However, RSC exacerbated mitochondrial dysfunction during HPX, resulting in decreased respiratory control index, decreased mitochondrial efficiency (phosphorylated ADP-to-oxygen consumed ratio), and increased noncoupled respiration (HPX/Con post- vs. preexercise). SR Ca2+ uptake rate was lower 0.3 vs. 24 h postexercise, whereas SR Ca2+ release rate was unchanged. RSC resulted in long-lasting changes in muscle contractility, including reduced maximal torque, low-frequency fatigue, and faster torque relaxation. It is concluded that RSC increases mitochondrial vulnerability toward ROS, reduces SR Ca2+ uptake rate, and causes low-frequency fatigue. Although conclusive evidence is lacking, we suggest that these changes are related to increased formation of ROS during RSC.

  • 290. Sahlin, Kent
    et al.
    Söderlund, Karin
    Tonkonogi, Michail
    Högskolan Dalarna, Akademin Hälsa och samhälle, Medicinsk vetenskap.
    Hirakoba, Koji
    Phosphocreatine content in single fibers of human muscle after sustained submaximal exercise.1997Ingår i: American Journal of Physiology. Heart and Circulatory Physiology, ISSN 0363-6135, E-ISSN 1522-1539, Vol. 273, s. C172-C178Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The effect of sustained submaximal exercise on muscle energetics has been studied on the single-fiber level in human skeletal muscle. Seven subjects cycled to fatigue (mean 77 min) at a work rate corresponding to approximately 75% of maximal O2 uptake. Biopsies were taken from the vastus lateralis muscle at rest, at fatigue, and after 5 min of recovery. Muscle glycogen decreased from 444 +/- 40 (SE) mmol glucosyl units/kg dry wt at rest to 94 +/- 16. Postexercise glycogen was inversely correlated (P < 0.01) to muscle content of inosine monophosphate, a catabolite of ATP. Phosphocreatine (PCr) in mixed-fiber muscle decreased at fatigue to 37% but was restored above the initial value (106.5%, P < 0.025) after 5 min of recovery. The overshoot was localized to type I fibers. The rapid reversal of PCr is in contrast to the slow recovery in contraction force. Pi increased at fatigue but less than that expected from the changes in PCr and other phosphate compounds. Mean PCr at rest was approximately 20% higher in type II than in type I fibers (86.4 +/- 3.6 and 71.6 +/- 1.8 mmol/kg dry wt, respectively, P < 0.05), but at fatigue similar PCr contents were observed in the two fiber types. Reduction in PCr in all fibers at fatigue suggests that all fibers were recruited at the end of exercise. PCr content in single fibers showed a great variability in samples at rest, exercise, and recovery. The variability was more pronounced than for ATP, and the data suggest that it is due to interfiber physiological-biochemical differences. At fatigue ATP was maintained relatively high in all single fibers, but a pronounced depletion of PCr was observed in a large number of fibers, and this may contribute to fatigue through the associated increases in Pi or/and free ADP. It is noteworthy that the increase in calculated free ADP at fatigue was similar to that after high-intensity exercise.

  • 291. Sahlin, Kent
    et al.
    Tonkonogi, Michail
    Högskolan Dalarna, Akademin Hälsa och samhälle, Medicinsk vetenskap.
    Söderlund, Karin
    Energy supply and muscle fatigue in humans.1998Ingår i: Acta Physiologica Scandinavica, ISSN 0001-6772, E-ISSN 1365-201X, Vol. 162, s. 261-266Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Limitations in energy supply is a classical hypothesis of muscle fatigue. The present paper reviews the evidence available from human studies that energy deficiency is an important factor in fatigue. The maximal rate of energy expenditure determined in skinned fibres is close to the rate of adenosine triphosphate (ATP) utilisation observed in vivo and data suggest that performance during short bursts of exercise (<5 s duration) primarily is limited by other factors than energy supply (e.g. Vmax of myosine adenosine triphosphatase (ATPase), motor unit recruitment, engaged muscle mass). Within 10 s of exercise maximal power output decreases considerably and coincides with depletion of phosphocreatine. During recovery, maximal force and power output is restored with a similar time course as the resynthesis of phosphocreatine. Increases in muscle store of phosphocreatine through dietary supplementation with creatine increases performance during high-intensity exercise. These findings support the hypothesis that energy supply limits performance during high-intensity exercise. It is well documented that pre-exercise muscle glycogen content is related to performance during moderate intensity exercise. Recent data indicates that the interfibre variation in phosphocreatine is large after prolonged exercise to fatigue and that some fibres are depleted to the same extent as after high-intensity exercise. Despite relatively small decreases in ATP, the products of ATP hydrolysis (Pi and free ADP) may increase considerably. FreeADP calculated from the creatine kinase reaction increases 10-fold both after high-intensity exercise and after prolonged exercise to fatigue. It is suggested that local increases in ADP may reach inhibitory levels for the contraction process.

  • 292. Sahlin, Kent
    et al.
    Tonkonogi, Michail
    Högskolan Dalarna, Akademin Hälsa och samhälle, Medicinsk vetenskap.
    Söderlund, Karin
    Plasma hypoxanthine and ammonia in humans during prolonged exercise.1999Ingår i: European Journal of Applied Physiology, ISSN 1439-6319, E-ISSN 1439-6327, Vol. 80, s. 417-422Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In this study we examined the time course of changes in the plasma concentration of oxypurines [hypoxanthine (Hx), xanthine and urate] during prolonged cycling to fatigue. Ten subjects with an estimated maximum oxygen uptake ( V?O 2max) of 54 (range 47–67) ml?·?kg -1?·?min -1 cycled at [mean?(SEM)] 74?(2)% of V?O 2max until fatigue [79?(8) min]. Plasma levels of oxypurines increased during exercise, but the magnitude and the time course varied considerably between subjects. The plasma concentration of Hx ([Hx]) was 1.3?(0.3)?µmol/l at rest and increased eight fold at fatigue. After 60?min of exercise plasma [Hx] was >10?µmol/l in four subjects, whereas in the remaining five subjects it was <5?µmol/l. The muscle contents of total adenine nucleotides (TAN?=?ATP+ADP+AMP) and inosine monophosphate (IMP) were measured before and after exercise in five subjects. Subjects with a high plasma [Hx] at fatigue also demonstrated a pronounced decrease in muscle TAN and increase in IMP. Plasma [Hx] after 60?min of exercise correlated significantly with plasma concentration of ammonia ([NH 3], r?=?0.90) and blood lactate ( r?=?0.66). Endurance, measured as time to fatigue, was inversely correlated to plasma [Hx] at 60?min ( r?=?-0.68, P?3] or blood lactate. It is concluded that during moderate-intensity exercise, plasma [Hx] increases, but to a variable extent between subjects. The present data suggest that plasma [Hx] is a marker of adenine nucleotide degradation and energetic stress during exercise. The potential use of plasma [Hx] to assess training status and to identify overtraining deserves further attention.

  • 293. Seppet, E. K.
    et al.
    Kaambre, T.
    Sikk, P.
    Tiivel, T.
    Vija, H.
    Kay, L.
    Appaix, F.
    Tonkonogi, Michail
    Högskolan Dalarna, Akademin Hälsa och samhälle, Medicinsk vetenskap.
    Sahlin, Kent
    Braun, U.
    Eimre, M.
    Saks, V.A.
    Functional complexes of mitochondria with MgATPase of myofibrils and sarcoplasmic reticulum in muscle cells2001Ingår i: Biochimica et Biophysica Acta - Bioenergetics, ISSN 0005-2728, E-ISSN 1879-2650, Vol. 1504, nr 2-3, s. 379-395Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Regulation of mitochondrial respiration in situ in the muscle cells was studied by using fully permeabilized muscle fibers and cardiomyocytes. The results show that the kinetics of regulation of mitochondrial respiration in situ by exogenous ADP are very different from the kinetics of its regulation by endogenous ADP. In cardiac and m. soleus fibers apparent Km for exogenous ADP in regulation of respiration was equal to 300–400 µM. However, when ADP production was initiated by intracellular ATPase reactions, the ADP concentration in the medium leveled off at about 40 µM when about 70% of maximal rate of respiration was achieved. Respiration rate maintained by intracellular ATPases was suppressed about 20–30% during exogenous trapping of ADP with excess pyruvate kinase (PK, 20 IU/ml) and phosphoenolpyruvate (PEP, 5 mM). ADP flux via the external PK+PEP system was decreased by half by activation of mitochondrial oxidative phosphorylation. Creatine (20 mM) further activated the respiration in the presence of PK+PEP. It is concluded that in oxidative muscle cells mitochondria behave as if they were incorporated into functional complexes with adjacent ADP producing systems – with the MgATPases in myofibrils and Ca,MgATPases of sarcoplasmic reticulum.

  • 294. Shlipak, Michael G
    et al.
    Matsushita, Kunihiro
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Inker, Lesley A
    Katz, Ronit
    Polkinghorne, Kevan R
    Rothenbacher, Dietrich
    Sarnak, Mark J
    Astor, Brad C
    Gansevoort, Ron T
    Cystatin C versus creatinine in determining risk based on kidney function2013Ingår i: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 369, nr 10, s. 932-943Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Adding the measurement of cystatin C to that of serum creatinine to determine the estimated glomerular filtration rate (eGFR) improves accuracy, but the effect on detection, staging, and risk classification of chronic kidney disease across diverse populations has not been determined.

    METHODS: We performed a meta-analysis of 11 general-population studies (with 90,750 participants) and 5 studies of cohorts with chronic kidney disease (2960 participants) for whom standardized measurements of serum creatinine and cystatin C were available. We compared the association of the eGFR, as calculated by the measurement of creatinine or cystatin C alone or in combination with creatinine, with the rates of death (13,202 deaths in 15 cohorts), death from cardiovascular causes (3471 in 12 cohorts), and end-stage renal disease (1654 cases in 7 cohorts) and assessed improvement in reclassification with the use of cystatin C.

    RESULTS: In the general-population cohorts, the prevalence of an eGFR of less than 60 ml per minute per 1.73 m(2) of body-surface area was higher with the cystatin C-based eGFR than with the creatinine-based eGFR (13.7% vs. 9.7%). Across all eGFR categories, the reclassification of the eGFR to a higher value with the measurement of cystatin C, as compared with creatinine, was associated with a reduced risk of all three study outcomes, and reclassification to a lower eGFR was associated with an increased risk. The net reclassification improvement with the measurement of cystatin C, as compared with creatinine, was 0.23 (95% confidence interval [CI], 0.18 to 0.28) for death and 0.10 (95% CI, 0.00 to 0.21) for end-stage renal disease. Results were generally similar for the five cohorts with chronic kidney disease and when both creatinine and cystatin C were used to calculate the eGFR.

    CONCLUSIONS: The use of cystatin C alone or in combination with creatinine strengthens the association between the eGFR and the risks of death and end-stage renal disease across diverse populations. (Funded by the National Kidney Foundation and others.).

  • 295. Shungin, Dmitry
    et al.
    Winkler, Thomas W
    Croteau-Chonka, Damien C
    Ferreira, Teresa
    Locke, Adam E
    Mägi, Reedik
    Strawbridge, Rona J
    Pers, Tune H
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Uppasla universitet.
    Mohlke, Karen L
    New genetic loci link adipose and insulin biology to body fat distribution2015Ingår i: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 518, nr 7538, s. 187-196Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 x 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.

  • 296. Sjöberg, B
    et al.
    Qureshi, A R
    Heimbürger, O
    Stenvinkel, P
    Lind, L
    Larsson, A
    Bárány, P
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Uppsala university.
    Association between levels of pentraxin 3 and incidence of chronic kidney disease in the elderly2016Ingår i: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 279, nr 2, s. 173-179Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: Higher levels of the novel inflammatory marker pentraxin 3 (PTX3) predict cardiovascular mortality in patients with chronic kidney disease (CKD). Yet, whether PTX3 predicts worsening of kidney function has been less well studied. We therefore investigated the associations between PTX3 levels, kidney disease measures and CKD incidence.

    METHODS: Cross-sectional associations between serum PTX3 levels, urinary albumin/creatinine ratio (ACR) and cystatin C-estimated glomerular filtration rate (GFR) were assessed in two independent community-based cohorts of elderly subjects: the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS, n = 768, 51% women, mean age 75 years) and the Uppsala Longitudinal Study of Adult Men (ULSAM, n = 651, mean age 77 years). The longitudinal association between PTX3 level at baseline and incident CKD (GFR <60 mL( ) min(-1)  1.73 m(-) ²) was also analysed (number of events/number at risk: PIVUS 229/746, ULSAM 206/315).

    RESULTS: PTX3 levels were inversely associated with GFR [PIVUS: B-coefficient per 1 SD increase -0.16, 95% confidence interval (CI) -0.23 to -0.10, P < 0.001; ULSAM: B-coefficient per 1 SD increase -0.09, 95% CI -0.16 to -0.01, P < 0.05], but not ACR, after adjusting for age, gender, C-reactive protein and prevalent cardiovascular disease in cross-sectional analyses. In longitudinal analyses, PTX3 levels predicted incident CKD after 5 years in both cohorts [PIVUS: multivariable odds ratio (OR) 1.21, 95% CI 1.01-1.45, P < 0.05; ULSAM: multivariable OR 1.37, 95% CI 1.07-1.77, P < 0.05].

    CONCLUSIONS: Higher PTX3 levels are associated with lower GFR and independently predict incident CKD in elderly men and women. Our data confirm and extend previous evidence suggesting that inflammatory processes are activated in the early stages of CKD and drive impairment of kidney function. Circulating PTX3 appears to be a promising biomarker of kidney disease.

  • 297. Skoglund, Per H
    et al.
    Höijer, Jonas
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Zethelius, Björn
    Svensson, Per
    Amino-terminal pro-B-type natriuretic peptide improves discrimination for incident atherosclerotic cardiovascular disease beyond ambulatory blood pressure in elderly men2015Ingår i: Hypertension, ISSN 0194-911X, E-ISSN 1524-4563, Vol. 66, nr 3, s. 681-686Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Improvement of risk prediction for atherosclerotic cardiovascular disease (ASCVD) is needed. Both ambulatory blood pressure (ABP) and biomarkers amino-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity C-reactive protein and cystatin C improve risk prediction but they have not been evaluated in relation to each other. We analyzed whether NT-proBNP, high-sensitivity C-reactive protein, or cystatin C improved risk prediction beyond traditional ASCVD risk factors combined with 24-hour systolic BP (SBP). Secondary aim was to evaluate whether ABP improved risk prediction when compared with models with the biomarkers. We followed up 907 70-year-old men, free of baseline disease, for incident ASCVD defined as fatal or nonfatal myocardial infarction or fatal or nonfatal stroke for a median of 10 years. Cox regression was used to estimate the association between variables in the models and incident ASCVD. Biomarkers were added to a model containing both traditional risk factors and ABP and the models were compared on C-statistics and net reclassification improvement. Twenty-four hour SBP improved discrimination for incident ASCVD when compared with office SBP in a traditional risk factor model (area under the receiver-operating characteristic curve, +2.4%). NT-proBNP further improved reclassification (+18.7%-19.9%; P<0.01) when added to ABP models, whereas high-sensitivity C-reactive protein and cystatin C did not. Twenty-four hour SBP significantly improved net reclassification when added to a traditional risk factor model that included NT-proBNP. The combination of 24-hour SBP and NT-proBNP improved discrimination and net reclassification for incident ASCVD when compared with office SBP in elderly men. NT-proBNP, but not high-sensitivity C-reactive protein or cystatin C, improved risk prediction and discrimination when added to a model that included ABP.

  • 298. Sobestiansky, S
    et al.
    Åberg, Anna Cristina
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Fugmann, A
    Cederholm, T
    Sarcopenia, anthropometry and malnutrition in relation to 2-y mortality in geriatric patients2014Konferensbidrag (Refereegranskat)
  • 299. Soveri, I
    et al.
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Berglund, L
    Lind, L
    Fellström, B
    Sundström, J
    Kidney function and discrimination of cardiovascular risk in middle-aged men2009Ingår i: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 266, nr 4, s. 406-413Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective. To define the optimal glomerular filtration rate (GFR) cut off for discriminating the risk of myocardial infarction or cardiovascular death. 

    Design. Prospective longitudinal observational study. Setting. A community-based cohort. 

    Participants. A total of 2176 nondiabetic 50-year-old men without cardiovascular disease. 

    Methods. The men were followed until age 70. GFR was estimated at baseline using the Cockcroft-Gault formula. The optimal GFR cut-off points for discriminating risk of a fatal or nonfatal myocardial infarction and cardiovascular death were defined as the GFR levels maximizing integrated discrimination improvement (IDI). 

    Main outcome measures. Fatal or nonfatal myocardial infarction, cardiovascular death. 

    Results. During follow-up, 264 men experienced a fatal or nonfatal myocardial infarction, and 218 died of cardiovascular disease. The IDI-defined optimal GFR cut offs in this study were 98 mL min-1 for discriminating myocardial infarction risk and 92 mL min-1 for discriminating risk of cardiovascular death. In Cox proportional hazard models adjusting for established risk factors, the myocardial infarction risk was substantially higher in men with GFR below versus above 98 mL min-1 [hazard ratio (HR) 1.7, 95% confidence interval (CI) 1.3-2.3, P < 0.001], and the risk of cardiovascular death was doubled in men with GFR below versus above 92 mL min-1 (HR 2.1, 95% CI 1.5-3.0, P < 0.001). 

    Conclusion. The GFR cut-off point for optimal discrimination of cardiovascular risk in the general population may be higher than previously suggested.

  • 300. Stanaway, Jeffrey D
    et al.
    Afshin, Ashkan
    Gakidou, Emmanuela
    Lim, Stephen S
    Abate, Degu
    Abate, Kalkidan Hassell
    Abbafati, Cristiana
    Abbasi, Nooshin
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Karolinska institutet.
    Murray, Christopher J. L
    Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 20172018Ingår i: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 392, nr 10159, s. 1923-1994Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 comparative risk assessment (CRA) is a comprehensive approach to risk factor quantification that offers a useful tool for synthesising evidence on risks and risk outcome associations. With each annual GBD study, we update the GBD CRA to incorporate improved methods, new risks and risk outcome pairs, and new data on risk exposure levels and risk outcome associations. 

    Methods We used the CRA framework developed for previous iterations of GBD to estimate levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs), by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or groups of risks from 1990 to 2017. This study included 476 risk outcome pairs that met the GBD study criteria for convincing or probable evidence of causation. We extracted relative risk and exposure estimates from 46 749 randomised controlled trials, cohort studies, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. Using the counterfactual scenario of theoretical minimum risk exposure level (TMREL), we estimated the portion of deaths and DALYs that could be attributed to a given risk. We explored the relationship between development and risk exposure by modelling the relationship between the Socio-demographic Index (SDI) and risk-weighted exposure prevalence and estimated expected levels of exposure and risk-attributable burden by SDI. Finally, we explored temporal changes in risk-attributable DALYs by decomposing those changes into six main component drivers of change as follows: (1) population growth; (2) changes in population age structures; (3) changes in exposure to environmental and occupational risks; (4) changes in exposure to behavioural risks; (5) changes in exposure to metabolic risks; and (6) changes due to all other factors, approximated as the risk-deleted death and DALY rates, where the risk-deleted rate is the rate that would be observed had we reduced the exposure levels to the TMREL for all risk factors included in GBD 2017. 

    Findings In 2017,34.1 million (95% uncertainty interval [UI] 33.3-35.0) deaths and 121 billion (144-1.28) DALYs were attributable to GBD risk factors. Globally, 61.0% (59.6-62.4) of deaths and 48.3% (46.3-50.2) of DALYs were attributed to the GBD 2017 risk factors. When ranked by risk-attributable DALYs, high systolic blood pressure (SBP) was the leading risk factor, accounting for 10.4 million (9.39-11.5) deaths and 218 million (198-237) DALYs, followed by smoking (7.10 million [6.83-7.37] deaths and 182 million [173-193] DALYs), high fasting plasma glucose (6.53 million [5.23-8.23] deaths and 171 million [144-201] DALYs), high body-mass index (BMI; 4.72 million [2.99-6.70] deaths and 148 million [98.6-202] DALYs), and short gestation for birthweight (1.43 million [1.36-1.51] deaths and 139 million [131-147] DALYs). In total, risk-attributable DALYs declined by 4.9% (3.3-6.5) between 2007 and 2017. In the absence of demographic changes (ie, population growth and ageing), changes in risk exposure and risk-deleted DALYs would have led to a 23.5% decline in DALYs during that period. Conversely, in the absence of changes in risk exposure and risk-deleted DALYs, demographic changes would have led to an 18.6% increase in DALYs during that period. The ratios of observed risk exposure levels to exposure levels expected based on SDI (O/E ratios) increased globally for unsafe drinking water and household air pollution between 1990 and 2017. This result suggests that development is occurring more rapidly than are changes in the underlying risk structure in a population. Conversely, nearly universal declines in O/E ratios for smoking and alcohol use indicate that, for a given SDI, exposure to these risks is declining. In 2017, the leading Level 4 risk factor for age-standardised DALY rates was high SBP in four super-regions: central Europe, eastern Europe, and central Asia; north Africa and Middle East; south Asia; and southeast Asia, east Asia, and Oceania. The leading risk factor in the high-income super-region was smoking, in Latin America and Caribbean was high BMI, and in sub-Saharan Africa was unsafe sex. O/E ratios for unsafe sex in sub-Saharan Africa were notably high, and those for alcohol use in north Africa and the Middle East were notably low. 

    Interpretation By quantifying levels and trends in exposures to risk factors and the resulting disease burden, this assessment offers insight into where past policy and programme efforts might have been successful and highlights current priorities for public health action. Decreases in behavioural, environmental, and occupational risks have largely offset the effects of population growth and ageing, in relation to trends in absolute burden. Conversely, the combination of increasing metabolic risks and population ageing will probably continue to drive the increasing trends in non-communicable diseases at the global level, which presents both a public health challenge and opportunity. We see considerable spatiotemporal heterogeneity in levels of risk exposure and risk-attributable burden. Although levels of development underlie some of this heterogeneity, O/E ratios show risks for which countries are overperforming or underperforming relative to their level of development. As such, these ratios provide a benchmarking tool to help to focus local decision making. Our findings reinforce the importance of both risk exposure monitoring and epidemiological research to assess causal connections between risks and health outcomes, and they highlight the usefulness of the GBD study in synthesising data to draw comprehensive and robust conclusions that help to inform good policy and strategic health planning.

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