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  • 201.
    Libungan, Berglind
    et al.
    Sahlgrens university hospital.
    Lindqvist, Jonny
    Sahlgrens university hospital.
    Strömsöe, Anneli
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Nordberg, Per
    Karolinska institutet.
    Hollenberg, Jacob
    Karolinska institutet.
    Albertsson, Per
    Sahlgrens university hospital.
    Karlsson, Thomas
    Göteborgs universitet.
    Herlitz, Johan
    Högskolan Väst.
    Out-of-hospital cardiac arrest in the elderly: a large-scale population-based study2015Ingår i: Resuscitation, ISSN 0300-9572, E-ISSN 1873-1570, Vol. 94, s. 28-32Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: There is little information on elderly people who suffer from out-of-hospital cardiac arrest (OHCA). Aim: To determine 30-day mortality and neurological outcome in elderly patients with OHCA.

    Methods: OHCA patients >= 70 years of age who were registered in the Swedish Cardiopulmonary Resuscitation Register between 1990 and 2013 were included and divided into three age categories (70-79, 80-89, and >= 90 years). Multiple logistic regression analyses were performed to identify independent predictors of 30-day survival.

    Results: Altogether, 36,605 cases were included in the study. Thirty-day survival was 6.7% in patients aged 70-79 years, 4.4% in patients aged 80-89 years, and 2.4% in those over 90 years. For patients with witnessed OHCA of cardiac aetiology found in a shockable rhythm, survival was higher: 20%, 15%, and 11%, respectively. In 30-day survivors, the distribution according to the cerebral performance categories (CPC) score at discharge from hospital was similar in the three age groups. In multivariate analysis, in patients over 70 years of age, the following factors were associated with increased chance of 30-day survival: younger age, OHCA outside the home, witnessed OHCA, CPR before arrival of EMS, shockable first-recorded rhythm, and short emergency response time.

    Conclusions: Advanced age is an independent predictor of mortality in OHCA patients over 70 years of age. However, even in patients above 90 years of age, defined subsets with a survival rate of more than 10% exist. In survivors, the neurological outcome remains similar regardless of age. 

  • 202. Liljedahl, S
    et al.
    Kahan, T
    Lind, L
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    The effects of antihypertensive treatment on the Doppler-derived myocardial performance index in patients with hypertensive left ventricular hypertrophy: results from the Swedish Irbesartan in Left Ventricular Hypertrophy Investigation versus Atenolol (SILVHIA)2009Ingår i: Echocardiography, ISSN 0742-2822, E-ISSN 1540-8175, Vol. 26, nr 7, s. 753-758Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives: To investigate the effects of antihypertensive treatment on the Doppler-derived myocardial performance index (MPI) in patients with hypertensive left ventricular hypertrophy. Methods: The MPI was measured at baseline and after 48 weeks of antihypertensive treatment in 93 participants of the SILVHIA trial, where individuals with primary hypertension and left ventricular hypertrophy were randomized to double blind treatment with either irbesartan or atenolol.

    Results: Antihypertensive treatment lowered MPI (mean difference -0.03 +/- 0.01, P = 0.04). Changes in MPI by treatment were associated with changes in left ventricular ejection fraction (beta-coefficient -0.35 P = 0.005), stroke volume pulse pressure (reflecting arterial compliance, beta-coefficient -0.39 P < 0.001) and peripheral vascular resistance (beta-coefficient 0.28 P < 0.04). Furthermore, there was a borderline significant association between changes in MPI and changes in E-wave deceleration time (reflecting diastolic function, beta-coefficient 0.23, P = 0.06). No associations were found between changes in MPI and changes in blood pressure, EA-ratio, left ventricular mass index, relative wall thickness or heart rate. A stepwise multivariable regression model confirmed the association between changes in MPI and changes in ejection fraction and stroke volume/pulse pressure (all P < 0.05), as well as the trend for E-wave deceleration time (P = 0.08), but not in the case of peripheral vascular resistance.

    Conclusion: The MPI exhibited a modest decrease after 48 weeks of antihypertensive treatment in patients with hypertensive left ventricular hypertrophy. Changes in MPI were associated with changes in left ventricular function and vascular compliance, rather than with changes in left ventricular remodeling or blood pressure. (ECHOCARDIOGRAPHY, Volume 26, August 2009)

  • 203. Lim, Stephen S
    et al.
    Allen, Kate
    Bhutta, Zulficiar
    Dandona, Lalit
    Forouzanfar, Mohammad H
    Fullman, Nancy
    Gething, Peter W
    Goldberg, Ellen M
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Murray, Christopher J. L
    Measuring the health-related Sustainable Development Goals in 188 countries: a baseline analysis from the Global Burden of Disease Study 20152016Ingår i: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 388, nr 10053, s. 1813-1850Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background In September, 2015, the UN General Assembly established the Sustainable Development Goals (SDGs). The SDGs specify 17 universal goals, 169 targets, and 230 indicators leading up to 2030. We provide an analysis of 33 health-related SDG indicators based on the Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015). 

    Methods We applied statistical methods to systematically compiled data to estimate the performance of 33 health-related SDG indicators for 188 countries from 1990 to 2015. We rescaled each indicator on a scale from 0 (worst observed value between 1990 and 2015) to 100 (best observed). Indices representing all 33 health-related SDG indicators (health-related SDG index), health-related SDG indicators included in the Millennium Development Goals (MDG index), and health-related indicators not included in the MDGs (non-MDG index) were computed as the geometric mean of the rescaled indicators by SDG target. We used spline regressions to examine the relations between the Socio-demographic Index (SDI, a summary measure based on average income per person, educational attainment, and total fertility rate) and each of the health-related SDG indicators and indices. 

    Findings In 2015, the median health-related SDG index was 59.3 (95% uncertainty interval 56.8-61.8) and varied widely by country, ranging from 85.5 (84.2-86.5) in Iceland to 20.4 (15.4-24.9) in Central African Republic. SDI was a good predictor of the health-related SDG index (r(2) = 0.88) and the MDG index (r(2) = 0.2), whereas the non-MDG index had a weaker relation with SDI (r(2) = 0.79). Between 2000 and 2015, the health-related SDG index improved by a median of 7.9 (IQR 5.0-10.4), and gains on the MDG index (a median change of 10.0 [6.7-13.1]) exceeded that of the non-MDG index (a median change of 5.5 [2.1-8.9]). Since 2000, pronounced progress occurred for indicators such as met need with modern contraception, under-5 mortality, and neonatal mortality, as well as the indicator for universal health coverage tracer interventions. Moderate improvements were found for indicators such as HIV and tuberculosis incidence, minimal changes for hepatitis B incidence took place, and childhood overweight considerably worsened. 

    Interpretation GBD provides an independent, comparable avenue for monitoring progress towards the health-related SDGs. Our analysis not only highlights the importance of income, education, and fertility as drivers of health improvement but also emphasises that investments in these areas alone will not be sufficient. Although considerable progress on the health-related MDG indicators has been made, these gains will need to be sustained and, in many cases, accelerated to achieve the ambitious SDG targets. The minimal improvement in or worsening of health-related indicators beyond the MDGs highlight the need for additional resources to effectively address the expanded scope of the health-related SDGs

  • 204. Lind, L
    et al.
    Ingelsson, E
    Sundström, J
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    The impact of obesity and the metabolic syndrome on the risk of cardiovascular morbidity and mortality in middle-aged men2009Ingår i: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 119, nr 10, s. E302-E302Artikel i tidskrift (Refereegranskat)
  • 205. Lind, L
    et al.
    Siegbahn, A
    Ingelsson, E
    Sundström, J
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    A detailed cardiovascular characterization of metabolically healthy obesity2009Ingår i: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 119, nr 10, s. E302-E302Artikel i tidskrift (Refereegranskat)
  • 206. Lind, L
    et al.
    Siegbahn, A
    Ingelsson, E
    Sundström, J
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    A detailed cardiovascular characterization of obesity without the metabolic syndrome2011Ingår i: Arteriosclerosis, Thrombosis and Vascular Biology, ISSN 1079-5642, E-ISSN 1524-4636, Vol. 31, nr 8, s. e27-e34Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: Although obesity without metabolic disturbances has been regarded as harmless, we have recently shown that obese subjects without the metabolic syndrome (MetS) has an increased risk of cardiovascular (CV) disorders and mortality during long-term follow-up. To investigate the basis for that increased risk, we studied the impact of obesity without MetS on multiple markers of subclinical CV disease.

    Methods and results: At age 70, 1016 subjects were investigated in the Prospective Investigation of the Vasculature in Uppsala Seniors study. According to body mass index (BMI)/MetS status, they were categorized as normal weight (BMI <25 kg/m2) without MetS (National Cholesterol Education Program criteria, n=319), normal weight with MetS (n=19), overweight (BMI 25 to 29.9 kg/m2) without MetS (n=333), overweight with MetS (n=94), obese (BMI =30 kg/m2) without MetS (n=102), and obese with MetS (n=118). Several different measurements of endothelial reactivity, arterial compliance (plethysmography and ultrasound), carotid artery atherosclerosis, and echocardiography were performed, and 7 markers of coagulation/fibrinolysis were measured. Subjects with obesity without MetS showed impaired vasoreactivity, a more echolucent carotid artery wall, increased left ventricular mass and function together with impaired coagulation/fibrinolysis compared with normal-weight subjects without the MetS (P<0.05 to 0.001). The majority of these disturbances were also seen in overweight subjects without the MetS.

    Conclusion: In contrast to some previous studies, our data do not support that obesity without MetS is a benign condition, because obesity without MetS was associated with impairments in multiple markers of subclinical CV disease. This was also the case for overweight subjects without the MetS.

  • 207. Lind, Lars
    et al.
    Carlsson, Axel C
    Siegbahn, Agneta
    Sundström, Johan
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Uppsala universitet.
    Impact of physical activity on cardiovascular status in obesity2017Ingår i: European Journal of Clinical Investigation, ISSN 0014-2972, E-ISSN 1365-2362, Vol. 47, nr 2, s. 167-175Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: We have recently shown that being physically active (PA) counteracts, but not eliminates the increased risk of future cardiovascular disease in over-weight and obese subjects. To investigate this further, we studied the impact of being normal weight, overweight and obese on multiple markers of subclinical cardiovascular disease in relation to physical activity.

    MATERIALS AND METHODS: At age 70, 1016 subjects were investigated in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. Being PA was defined as performing regular heavy exercise (self-reported). According to body mass index (BMI)/PA-groups, the participants were categorized as PA/normal weight (BMI <25 kg/m(2) , n=104), non-PA/normal weight (n=234), PA/overweight (BMI 25-29.9 kg/m(2) , n=133), non-PA/overweight (n=295), PA/obese (BMI ≥30 kg/m(2) , n=54), and non-PA/obese (n=169). Several different measurements of endothelial reactivity and arterial compliance (plethysmography and ultrasound), cartotid artery atherosclerosis and echocardiography were performed and seven markers of coagulation/fibrinolysis were measured.

    RESULTS: Physically activite subjects with obesity showed impaired vasoreactivity in the forearm resistance vessels, increased left ventricular mass and impaired left ventricular systolic and diastolic function, together with impaired coagulation/fibrinolysis when compared to PA/normal weight subjects (p<0.05- <0.001). The majority of these disturbances were seen also in PA/overweight subjects when compared to PA/normal weight subjects (p<0.05- <0.001).

    CONCLUSIONS: Our data provide additional support for the notion that an increased level of self-reported physical activity does not fully eliminate the deleterious cardiovascular consequences associated with overweight and obesity. This article is protected by copyright. All rights reserved.

  • 208. Lind, Lars
    et al.
    Elmståhl, Sölve
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Uppsala universitet.
    Change in body weight from age 20 years is a powerful determinant of the metabolic syndrome2017Ingår i: Metabolic Syndrome and Related Disorders, ISSN 1540-4196, E-ISSN 1557-8518, Vol. 15, nr 3, s. 112-117Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Higher body weight is a well-known determinant of the metabolic syndrome (MetS) and its components. It is however less well studied how the change in weight from age 20 years to middle age or old age affects MetS development.

    METHODS: In the community-based EpiHealth (n = 19,000, age range 45 to 75 years, 56% females) and PIVUS (n = 1000, all aged 70 years, 50% females) studies, the participants were asked about their body weight at age 20 years. Data were collected to determine MetS prevalence (NCEP ATP III criteria).

    RESULTS: In EpiHealth, the probability of having MetS increased fairly linearly with increasing weight from age 20 in the obese [odds ratios (OR) 1.04 per kg change in weight, 95% confidence interval (CI) 1.03-1.05, P < 0.0001], as well as in the overweight (OR 1.15, 95% CI 1.14-1.17, P < 0.0001) and normal-weight (OR 1.18, 95% CI 1.14-1.21, P < 0.0001), subjects after adjustment for age, sex, body mass index (BMI) at age 20, alcohol intake, smoking, education, and exercise habits. Also in the PIVUS study, the change in weight over 50 years was related to prevalent MetS (OR 1.08 per kg change in weight, 95% CI 1.06-1.10, P < 0.0001). In both studies, self-reported BMI at age 20 was related to prevalent MetS.

    CONCLUSION: Self-reported weight gain from age 20 was strongly and independently associated with prevalent MetS both in middle age or old age. Interestingly, this relationship was not restricted only to obese subjects. Our data provide additional support for the importance of maintaining a stable weight throughout life.

  • 209. Lind, Lars
    et al.
    Ingelsson, Erik
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Karolinska Institutet.
    Sundström, Johan
    Zethelius, Björn
    Reaven, Gerald M
    Can the Plasma Concentration Ratio of Triglyceride/High-Density Lipoprotein Cholesterol Identify Individuals at High Risk of Cardiovascular Disease During 40-Year Follow-Up?2018Ingår i: Metabolic Syndrome and Related Disorders, ISSN 1540-4196, E-ISSN 1557-8518, Vol. 16, nr 8, s. 433-439Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: The plasma concentration ratio of triglyceride (TG)/high-density lipoprotein cholesterol (HDL-C) is a simple way to estimate insulin resistance. We aimed to evaluate the TG/HDL-C ratio as a simple clinical way to identify apparently healthy individuals with insulin resistance and enhanced risk of future cardiovascular disease (CVD).

    METHODS: One thousand seven hundred twenty men, aged 50 years, free from diabetes and CVD when evaluated at baseline in 1970-1974 were followed for 40 years regarding incident CVD (myocardial infarction and/or ischemic stroke, n = 576).

    RESULTS: Participants with a high TG/HDL-C ratio (highest quartile >1.8) at baseline were more insulin resistant, with a significantly more adverse cardiometabolic risk profile (P < 0.001) at baseline, compared with those with a lower ratio. This group also showed an increased risk of CVD [hazard ratio, HR 1.47 (95% confidence interval 1.26-1.93) P < 0.001]. Fourteen percent of subjects with metabolic syndrome, in whom insulin resistance is increased, were also at enhanced CVD risk [HR 1.75 (1.42-2.16) P < 0.001].

    CONCLUSIONS: Twenty-five percent of apparently healthy 50-year-old men with the highest TG/HDL-C plasma concentration ratio had a significantly more adverse cardiometabolic profile at baseline, and developed more CVD over the next 40 years, compared with those not meeting this cut point. Determining the TG/HDL-C ratio in middle-aged men provided a simple and potentially clinically useful way to identify increased risk of developing CVD in persons free of diabetes or manifest CVD.

  • 210. Lind, Lars
    et al.
    Siegbahn, Agneta
    Lindahl, Bertil
    Stenemo, Markus
    Sundström, Johan
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Discovery of new risk markers for ischemic stroke using a novel targeted proteomics chip2015Ingår i: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 46, nr 12, s. 3340-3347Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND AND PURPOSE: Emerging technologies have made it possible to simultaneously evaluate a large number of circulating proteins as potential new stroke risk markers.

    METHODS: We explored associations between 85 cardiovascular proteins, assessed by a proteomics chip, and incident ischemic stroke in 2 independent cohorts of elderly (Prospective Investigation of the Vasculature in Uppsala Seniors [PIVUS]: n=977; 50% women, mean age=70.1 years, 71 fatal/nonfatal ischemic stroke events during 10.0 years; and Uppsala Longitudinal Study in Adult Men [ULSAM]: n=720, mean age=77.5 years, 75 ischemic stroke events during 9.5 years). The proteomics chip uses 2 antibodies for each protein and a polymerase chain reaction step to achieve a high-specific binding and the possibility to measure multiple proteins in parallel, but gives no absolute concentrations.

    RESULTS: In PIVUS, 16 proteins were related to incident ischemic stroke using a false discovery rate of 5%. Of these, N-terminal pro-B-type natriuretic peptide (P=0.0032), adrenomedullin (P=0.018), and eosinophil cationic protein (P=0.0071) were replicated in ULSAM after adjustment for established stroke risk factors. In predefined secondary meta-analyses of individual data, interleukin-27 subunit α, growth/differentiation factor 15, urokinase plasminogen activator surface receptor, tumor necrosis factor receptor superfamily member 6, macrophage colony-stimulating factor 1, and matrix metalloproteinase-7 were also potential risk markers for ischemic stroke after adjustment for multiple comparisons (P<0.0006). The addition of N-terminal pro-B-type natriuretic peptide, adrenomedullin, and eosinophil cationic protein to a model with established risk factors increased the C-statistic from 0.629 to 0.689 (P=0.001).

    CONCLUSIONS: Our data suggest that large-scale proteomics analysis is a promising way of discovering novel biomarkers that could substantially improve the prediction of ischemic stroke.

  • 211. Lind, Lars
    et al.
    Sundström, Johan
    Larsson, Anders
    Lampa, Erik
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Karolinska Institutet.
    Ingelsson, Erik
    Longitudinal effects of aging on plasma proteins levels in older adults: associations with kidney function and hemoglobin levels2019Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 14, nr 2, artikel-id e0212060Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: A targeted proteomics chip has been shown to be useful to discover novel associations of proteins with cardiovascular disease. We investigated how these proteins change with aging, and whether this change is related to a decline in kidney function, or to a change in hemoglobin levels.

    MATERIAL AND METHODS: In the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study, including 1,016 participants from the general population aged 70 at baseline, 84 proteins were measured at ages 70, 75, 80. At these occasions, glomerular filtration rate (eGFR) was estimated and the hemoglobin levels were measured.

    RESULTS: Sixty-one of the 84 evaluated proteins changed significantly during the 10-year follow-up (multiple testing-adjusted alpha = 0.00059), most showing an increase. The change in eGFR was inversely related to changes of protein levels for the vast majority of proteins (74%). The change in hemoglobin was significantly related to the change in 40% of the evaluated proteins, with no obvious preference of the direction of these relationships.

    CONCLUSION: The majority of evaluated proteins increased with aging in adults. Therefore, normal ranges for proteins might be given in age-strata. The increase in protein levels was associated with the degree of reduction in eGFR for the majority of proteins, while no clear pattern was seen for the relationships between the proteins and the change in hemoglobin levels. Studies on changes in urinary proteins are warranted to understand the association between the reduction in eGFR and increase in plasma protein levels.

  • 212. Lind, Lars
    et al.
    Sundström, Johan
    Stenemo, Markus
    Hagström, Emil
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Uppsala university.
    Discovery of new biomarkers for atrial fibrillation using a custom-made proteomics chip.2017Ingår i: Heart, ISSN 1355-6037, E-ISSN 1468-201X, Vol. 103, nr 5, s. 377-382Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Apart from several established clinical risk factors for atrial fibrillation (AF), a number of biomarkers have also been identified as potential risk factors for AF. None of these have so far been adopted in clinical practice.

    OBJECTIVE: To use a novel custom-made proteomics chip to discover new prognostic biomarkers for AF risk.

    METHODS: In two independent community-based cohorts (Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study (978 participants without AF, mean age 70.1 years, 50% women, median follow-up 10.0 years) and Uppsala Longitudinal Study of Adult Men (ULSAM) (n=725, mean age 77.5 years, median follow-up 7.9 years)), ninety-two plasma proteins were assessed at baseline by a proximity extension assay (PEA) chip. Of those, 85 proteins showed a call rate >70% in both cohorts.

    RESULTS: Thirteen proteins were related to incident AF in PIVUS (148 events) using a false discovery rate of 5%. Of those, five were replicated in ULSAM at nominal multivariable p value (123 events, N-terminal pro-B-type natriuretic peptide (NT-pro-BNP), fibroblast growth factor 23 (FGF-23), fatty acid-binding protein 4 (FABP4), growth differentiation factor 15 (GDF-15) and interleukin-6 (IL-6)). Of those, NT-pro-BNP and FGF-23 were also associated with AF after adjusting for established AF risk factors. In a prespecified secondary analysis pooling the two data sets, T-cell immunoglobulin and mucin domain 1 (TIM-1) and adrenomedullin (AM) were also significantly related to incident AF in addition to the aforementioned five proteins (Bonferroni-adjustment). The addition of NT-pro-BNP to a model with established risk factors increased the C-statistic from 0.605 to 0.676 (p<0.0001).

    CONCLUSIONS: Using a novel proteomics approach, we confirmed the previously reported association between NT-pro-BNP, FGF-23, GDF-15 and incident AF, and also discovered four proteins (FABP4, IL-6, TIM-1 and AM) that could be of importance in the development of AF.

  • 213. Lind, Lars
    et al.
    Sundström, Johan
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Karolinska institutet.
    Ingelsson, Erik
    Proteomic profiling of endothelium-dependent vasodilation2019Ingår i: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 37, nr 1, s. 216-222Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: As endothelial dysfunction is an early event in atherosclerosis formation, we investigated if proteins previously related to cardiovascular disease also were related to endothelial function using a novel targeted proteomics approach.

    METHODS: In the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study (n = 850-970, all aged 70 years), endothelium-dependent vasodilation (EDV) in the forearm was assessed by intra-arterial infusion of acetylcholine. Flow-mediated vasodilation (FMD) was investigated in the brachial artery by ultrasound. The same investigations were carried out in the Prospective investigation of Obesity, Energy and Metabolism (POEM) study (n = 375-461, all aged 50 years). After strict quality control, 84 cardiovascular-related proteins measured by the proximity extension assay were studied in relation to EDV and FMD in PIVUS (discovery sample) and POEM (validation sample).

    RESULTS: Of the 15 proteins being significantly related to EDV in PIVUS (false discovery rate <0.025), seven could be replicated in POEM at nominal significance and same effect direction when adjusted for sex and storage time. Of those, only cathepsin D remained significant following further adjustment for traditional cardiovascular risk factors (beta, -0.08; 95% confidence interval, -0.16, -0.01; P = 0.033; change in ln-transformed EDV per 1-SD increase in protein level). No protein was significantly related to FMD.

    CONCLUSION: Using a discovery/validation approach in two samples, our results indicate an inverse association between plasma cathepsin D levels and endothelial-dependent vasodilation.

  • 214. Lind, Lars
    et al.
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Lindahl, Bertil
    Siegbahn, Agneta
    Sundström, Johan
    Ingelsson, Erik
    Use of a proximity extension assay proteomics chip to discover new biomarkers for human atherosclerosis2015Ingår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 242, nr 1, s. 205-210Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND AND AIMS: We used a proteomics array to simultaneously measure multiple proteins that have been suggested to be associated with atherosclerosis and related them to plaque prevalence in carotid arteries in a human population-based study.

    METHODS: In the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS; n = 931, 50% women, all aged 70 years), the number of carotid arteries with plaques was recorded by ultrasound. Levels of 82 proteins were assessed in plasma by a proximity extension assay (Proseek Multiplex CVD, Olink Bioscience, Uppsala, Sweden) and related to carotid measures in a regression framework.

    RESULTS: Following adjustment for multiple testing with Bonferroni correction, seven of the proteins were significantly related to the number of carotid arteries affected by plaques in sex-adjusted models (osteoprotegrin, T-cell immunoglobulin and mucin domain (TIM)-1, growth/differentiation factor 15 (GDF-15), matrix metalloprotease-12 (MMP-12), renin, tumor necrosis factor ligand superfamily member 14 (TNFSF14) and growth hormone). Of these, renin (odds ratio [OR], 1.30; 95% confidence interval [CI], 1.13-1.49 per standard deviation increase), growth hormone (OR, 1.24; 95% CI, 1.08-1.43), osteoprotegerin (OR, 1.22; 95% CI, 1.05-1.43) and TNFSF14 (OR, 1.17; 95% CI, 1.01-1.35) were related to plaque prevalence independently of each other and traditional cardiovascular risk factors.

    CONCLUSION: A novel targeted proteomics approach using the proximity extension technique discovered several new associations of candidate proteins with carotid artery plaque prevalence in a large human sample.

  • 215.
    Lindgren, Helena
    et al.
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Christensson, Kyllike
    Rådestad, Ingela
    Hildingsson, Ingegerd
    Outcome of planned home births vs hospital births in Sweden between 1992 and 2004.2008Ingår i: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 87, nr 7, s. 751-759Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective The aim of this population based study was to measure the risk of adverse outcome for mother and child in planned home births in a Swedish population, irrespective of where the birth actually occurred, at home or in hospital after transfer. Design A population based study using data from the Swedish Medical Birth Register. Setting Sweden 1992-2004. Participants A total of 897 planned home births were compared with a randomly selected group of 11 341 planned hospital births. We also compared mortality rates with a national sample of 1 122 250 singleton, full-term babies. Main outcome measures Prevalence of mortality and morbidity among mothers and children, emergency conditions, instrumental and operative delivery and perineal lacerations were compared. Results During this period in Sweden the neonatal mortality rate was 2.2 per thousand in the home birth group and 0.7 in the hospital group (RR 3.6, 95% CI 0.2-14.7). No cases of emergency complications were found in the home birth group. The risk of having a sphincter rupture was lower in the planned home birth group (RR 0.2, 95% CI 0.0-0.7). The risk of having a caesarean section (RR 0.4, 95% CI 0.2-0.7) or instrumental delivery (RR 0.3, 95% CI 0.2-0.5) was significantly lower in the planned home birth group. Conclusion In Sweden, between 1992 and 2004, the intrapartum and neonatal mortality in planned home births was 2.2 per thousand. The proportion is higher compared to hospital births but no statistically significant difference. Women in the home birth group more often experienced a spontaneous birth without medical intervention and were less likely to sustain pelvic floor injuries.

  • 216.
    Lindgren, Helena
    et al.
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Hildingsson, Ingegerd
    Haglund, Bengt
    Rådestad, Ingela J
    Characteristics of women giving birth at home in Sweden: a national register study.2006Ingår i: American Journal of Obstetrics and Gynecology, ISSN 0002-9378, E-ISSN 1097-6868, Vol. 195, nr 5, s. 1366-1372Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: The objective of the study was to estimate the proportion of planned home births in Sweden and to identify maternal characteristics of women giving birth at home. Study design: This case-control study included register data of births from 1992 to 2001 in 352 women giving birth at home and 1760 women giving birth in a hospital. Results: Four hundred thirty-nine out-of-hospital births were found during the study period (0.5%). The proportion of planned home births was less than 0.4%. Women with home birth were more likely to have 4 children or more (odds ratio 3.7 [1.4 to 9.9]), be born in a European country outside Sweden (odds ratio 3.5 [1.8 to 6.8]), have a family income below the median (odds ratio 2.9 [2.0 to 4.1]), not work outside the home (odds ratio 2.4 [1.7 to 3.5]), have a high level of education (odds ratio 2.1 [1.5 to 3.0]), and be older than 35 years (odds ratio 1.7 [1.1 to 2.5]). Conclusion: Women with planned home births appear to be a group having a different lifestyle, compared with Swedish women in general.

  • 217.
    Lindkvist, Jenny
    et al.
    Högskolan Dalarna, Akademin Industri och samhälle, Kemiteknik.
    Malm, Mikaela
    Högskolan Dalarna, Akademin Industri och samhälle, Kemiteknik.
    Bergqvist, Yngve
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Straightforward and rapid determination of sulfadoxine and sulfamethoxazole in capillary blood on sampling paper with liquid chromatography and UV detection2009Ingår i: Transactions of the Royal Society of Tropical Medicine and Hygiene, ISSN 0035-9203, E-ISSN 1878-3503, Vol. 103, nr 4, s. 371-376Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A method for the determination of sulfadoxine and sulfamethoxazole in capillary blood on sampling paper has been developed and validated. The method is straightforward with minimal sample preparation, and is suitable for rural settings. Separation of sulfadoxine, sulfamethoxazole and internal standard was performed using a Purospher STAR RP-18 endcapped LC column (150 x 4.6 mm) with a mobile phase consisting of acetonitrile: sodium acetate buffer pH 5.2, 1=0.1 (1:2, v/v). For sulfadoxine, the within-day precision was 5.3% at 15 mu mol/l and 3.7% at 600 mu mol/l, while for sulfamethoxazole it was 5.7% at 15 mu mol/l and 3.8% at 600 mu mol/l. The tower limit of quantification was determined to 5 mu mol/l and precision was 5.5% and 5.0% for sulfadoxine and sulfamethoxazole, respectively.

  • 218.
    Lindqvist, Per
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Människan i den slutna psykiatriska vården2012Bok (Övrig (populärvetenskap, debatt, mm))
  • 219. Lo Martire, Riccardo
    et al.
    de Alwis, Manudul Pahansen
    Äng, Björn
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Karolinska institutet.
    Garme, Karl
    Construction of a web-based questionnaire for longitudinal investigation of work exposure, musculoskeletal pain and performance impairments in high-performance marine craft populations2017Ingår i: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 7, nr 7, artikel-id e016006Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: High-performance marine craft personnel (HPMCP) are regularly exposed to vibration and repeated shock (VRS) levels exceeding maximum limitations stated by international legislation. Whereas such exposure reportedly is detrimental to health and performance, the epidemiological data necessary to link these adverse effects causally to VRS are not available in the scientific literature, and no suitable tools for acquiring such data exist. This study therefore constructed a questionnaire for longitudinal investigations in HPMCP.

    METHODS: A consensus panel defined content domains, identified relevant items and outlined a questionnaire. The relevance and simplicity of the questionnaire's content were then systematically assessed by expert raters in three consecutive stages, each followed by revisions. An item-level content validity index (I-CVI) was computed as the proportion of experts rating an item as relevant and simple, and a scale-level content validity index (S-CVI/Ave) as the average I-CVI across items. The thresholds for acceptable content validity were 0.78 and 0.90, respectively. Finally, a dynamic web version of the questionnaire was constructed and pilot tested over a 1-month period during a marine exercise in a study population sample of eight subjects, while accelerometers simultaneously quantified VRS exposure.

    RESULTS: Content domains were defined as work exposure, musculoskeletal pain and human performance, and items were selected to reflect these constructs. Ratings from nine experts yielded S-CVI/Ave of 0.97 and 1.00 for relevance and simplicity, respectively, and the pilot test suggested that responses were sensitive to change in acceleration and that the questionnaire, following some adjustments, was feasible for its intended purpose.

    CONCLUSIONS: A dynamic web-based questionnaire for longitudinal survey of key variables in HPMCP was constructed. Expert ratings supported that the questionnaire content is relevant, simple and sufficiently comprehensive, and the pilot test suggested that the questionnaire is feasible for longitudinal measurements in the study population.

  • 220. Locke, Adam E
    et al.
    Kahali, Bratati
    Berndt, Sonja I
    Justice, Anne E
    Pers, Tune H
    Day, Felix R
    Powell, Corey
    Vedantam, Sailaja
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Speliotes, Elizabeth K
    Genetic studies of body mass index yield new insights for obesity biology2015Ingår i: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 515, nr 7538, s. 197-206Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in upto 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 x 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for similar to 2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous systemin obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.

  • 221. Lozano, Rafael
    et al.
    Fullman, Nancy
    Abate, Degu
    Abay, Solomon
    Abbafati, Cristiana
    Abbasi, Nooshin
    Abbastabar, Hedayat
    Abd-Allah, Foad
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Karolinska institutet.
    Murray, Christopher J. L
    Measuring progress from 1990 to 2017 and projecting attainment to 2030 of the health-related Sustainable Development Goals for 195 countries and territories: 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. 091-2138Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background Efforts to establish the 2015 baseline and monitor early implementation of the UN Sustainable Development Goals (SDGs) highlight both great potential for and threats to improving health by 2030. To fully deliver on the SDG aim of "leaving no one behind", it is increasingly important to examine the health-related SDGs beyond national-level estimates. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017), we measured progress on 41 of 52 health -related SDG indicators and estimated the health-related SDG index for 195 countries and territories for the period 1990-2017, projected indicators to 2030, and analysed global attainment. 

    Methods We measured progress on 41 health-related S DG indicators from 1990 to 2017, an increase of four indicators since GBD 2016 (new indicators were health worker density, sexual violence by non-intimate partners, population census status, and prevalence of physical and sexual violence [reported separately]). We also improved the measurement of several previously reported indicators. We constructed national-level estimates and, for a subset of health-related SDGs, examined indicator-level differences by sex and Socio-demographic Index (SDI) quintile. We also did subnational assessments of performance for selected countries. To construct the health related SDG index, we transformed the value for each indicator on a scale of 0-100, with 0 as the 2.5th percentile and 100 as the 97.5th percentile of 1000 draws calculated from 1990 to 2030, and took the geometric mean of the scaled indicators by target. To generate projections through 2030, we used a forecasting framework that drew estimates from the broader GBD study and used weighted averages of indicator-specific and country-specific annualised rates of change from 1990 to 2017 to inform future estimates. We assessed attainment of indicators with defined targets in two ways: first, using mean values projected for 2030, and then using the probability of attainment in 2030 calculated from 1000 draws. We also did a global attainment analysis of the feasibility of attaining SDG targets on the basis of past trends. Using 2015 global averages of indicators with defined SDG targets, we calculated the global annualised rates of change required from 2015 to 2030 to meet these targets, and then identified in what percentiles the required global annualised rates of change fell in the distribution of country-level rates of change from 1990 to 2015. We took the mean of these global percentile values across indicators and applied the past rate of change at this mean global percentile to all health-related SDG indicators, irrespective of target definition, to estimate the equivalent 2030 global average value and percentage change from 2015 to 2030 for each indicator. 

    Findings The global median health-related SDG index in 2017 was 59.4 (IQR 35.4-67.3), ranging from a low of 11.6 (95% uncertainty interval 9.6-14.0) to a high of 84.9 (83.1-86.7). SDG index values in countries assessed at the subnational level varied substantially particularly in China and India, although scores in Japan and the UK were more homogeneous. Indicators also varied by SDI quintile and sex, with males having worse outcomes than females for non-communicable disease (NCD) mortality, alcohol use, and smoking, among others. Most countries were projected to have a higher health-related SDG index in 2030 than in 2017, while country-level probabilities of attainment by 2030 varied widely by indicator. Under-5 mortality, neonatal mortality, maternal mortality ratio, and malaria indicators had the most countries with at least 95% probability of target attainment. Other indicators, including NCD mortality and suicide mortality, had no countries projected to meet corresponding SDG targets on the basis of projected mean values for 2030 but showed some probability of attaimnent by 2030. For some indicators, including child malnutrition, several infectious diseases, and most violence measures, the annualised rates of change required to meet SDG targets far exceeded the pace of progress achieved by any country in the recent past. We found that applying the mean global annualised rate of change to indicators without defined targets would equate to about 19% and 22% reductions in global smoking and alcohol consumption, respectively; a 47% decline in adolescent birth rates; and a more than 85% increase in health worker density per 1000 population by 2030. 

    Interpretation The GBD study offers a unique, robust platform for monitoring the health -related SDGs across demographic and geographic dimensions. Our findings underscore the importance of increased collection and analysis of disaggregated data and highlight where more deliberate design or targeting of interventions could accelerate progress in attaining the SDGs. Current projections show that many health -related SDG indicators, NCDs, NCD-related risks, and violence -related indicators will require a concerted shift away from what might have driven past gains curative interventions in the case of NCDs towards multisectoral, prevention -oriented policy action and investments to achieve SDG aims. Notably, several targets, if they are to be met by 2030, demand a pace of progress that no country has achieved in the recent past. The future is fundamentally uncertain, and no model can fully predict what breakthroughs or events might alter the course of the S DGs. What is clear is that our actions or inaction today will ultimately dictate how close the world, collectively, can get to leaving no one behind by 2030. 

  • 222.
    Luis, Desiree
    et al.
    Divisions of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention, and Technology, Karolinska Institutet, K56, Karolinska University Hospital Huddinge, S-141 86 Stockholm, Sweden.
    Huang, Xiaoyan
    Divisions of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention, and Technology, Karolinska Institutet, K56, Karolinska University Hospital Huddinge, S-141 86 Stockholm, Sweden ; Division of Nephrology, Peking University Shenzhen Hospital, Shenzhen, People's Republic of China.
    Sjögren, Per
    Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism, Uppsala University, Uppsala, Sweden.
    Risérus, Ulf
    Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism, Uppsala University, Uppsala, Sweden.
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Department of Public Health and Caring Sciences, Section of Geriatrics, Uppsala University, Uppsala, Sweden.
    Lindholm, Bengt
    Divisions of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention, and Technology, Karolinska Institutet, K56, Karolinska University Hospital Huddinge, S-141 86 Stockholm, Sweden.
    Cederholm, Tommy
    Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism, Uppsala University, Uppsala, Sweden.
    Carrero, Juan Jesus
    Divisions of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention, and Technology, Karolinska Institutet, K56, Karolinska University Hospital Huddinge, S-141 86 Stockholm, Sweden ; Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
    Renal function associates with energy intake in elderly community-dwelling men2014Ingår i: British Journal of Nutrition, ISSN 0007-1145, E-ISSN 1475-2662, Vol. 111, nr 12, s. 2184-2189Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Energy intake and renal function decrease with age. In patients with chronic kidney disease (CKD), spontaneous food intake decreases in parallel with the loss of renal function. The objective of the present study was to evaluate a possible relationship between renal dysfunction and energy intake in elderly community-dwelling men. A cross-sectional study including 1087 men aged 70 years from the Uppsala Longitudinal Study of Adult Men (ULSAM) community-based cohort was carried out. Dietary intake was assessed using 7 d food records, and glomerular filtration rate was estimated from serum cystatin C concentrations. Energy intake was normalised by ideal body weight, and macronutrient intake was energy-adjusted. The median normalised daily energy intake was 105 (interquartile range 88-124) kJ, and directly correlated with estimated glomerular filtration rate (eGFR) as determined by univariate analysis. Across the decreasing quartiles of eGFR, a significant trend of decreasing normalised energy intake was observed (P =0·01). A multivariable regression model including lifestyle factors and co-morbidities was used for predicting total energy intake. In this model, regular physical activity (standardised β = 0·160; P =0·008), smoking (standardised β = - 0·081; P =0·008), hypertension (standardised β = - 0·097; P =0·002), hyperlipidaemia (standardised β = - 0·064; P =0·037) and eGFR (per sd increase, standardised β = 0·064; P =0·04) were found to be independent predictors of energy intake. Individuals with manifest CKD (eGFR < 60 ml/min per 1·73 m2) were more likely to have lower energy intake than those without. In conclusion, there was a direct and independent correlation between renal function and energy intake in a population-based cohort of elderly men. We speculate on a possible link between renal dysfunction and malnutrition in the elderly.

  • 223. Lundell, S.
    et al.
    Tistad, Malin
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Omvårdnad.
    Rehn, B.
    Wiklund, M.
    Holmner, Å.
    Wadell, K.
    Building COPD care on shaky ground: A mixed methods study from Swedish primary care professional perspective2017Ingår i: BMC Health Services Research, ISSN 1472-6963, E-ISSN 1472-6963, Vol. 17, nr 1, artikel-id 467Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Chronic obstructive pulmonary disease (COPD) is a public health problem. Interprofessional collaboration and health promotion interventions such as exercise training, education, and behaviour change are cost effective, have a good effect on health status, and are recommended in COPD treatment guidelines. There is a gap between the guidelines and the healthcare available to people with COPD. The aim of this study was to increase the understanding of what shapes the provision of primary care services to people with COPD and what healthcare is offered to them from the perspective of healthcare professionals and managers.

    Methods: The study was conducted in primary care in a Swedish county council during January to June 2015. A qualitatively driven mixed methods design was applied. Qualitative and quantitative findings were merged into a joint analysis. Interviews for the qualitative component were performed with healthcare professionals (n = 14) from two primary care centres and analysed with qualitative content analysis. Two questionnaires were used for the quantitative component; one was answered by senior managers or COPD nurses at primary care centres (n = 26) in the county council and the other was answered by healthcare professionals (n = 18) at two primary care centres. The questionnaire data were analysed with descriptive statistics.

    Results: The analysis gave rise to the overarching theme building COPD care on shaky ground. This represents professionals driven to build a supportive COPD care on 'shaky' organisational ground in a fragmented and non-compliant healthcare organisation. The shaky ground is further represented by uninformed patients with a complex disease, which is surrounded with shame. The professionals are autonomous and pragmatic, used to taking responsibility for their work, and with limited involvement of the management. They wish to provide high quality COPD care with interprofessional collaboration, but they lack competence and are hindered by inadequate routines and lack of resources.

    Conclusions: There is a gap between COPD treatment guidelines and the healthcare that is provided in primary care. To facilitate implementation of the guidelines several actions are needed, such as further training for professionals, additional resources, and improved organisational structure for interprofessional collaboration and patient education. 

  • 224. Lupo, Corrado
    et al.
    Guidotti, Flavia
    Goncalves, Carlos E.
    Moreira, Liliana
    Doupona Topic, Mojca
    Bellardini, Helena
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Idrotts- och hälsovetenskap.
    Tonkonogi, Michail
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Colin, Allen
    Capranica, Laura
    Motivation towards dual career of European student-athletes2015Ingår i: European Journal of Sport Science, ISSN 1746-1391, E-ISSN 1536-7290, Vol. 15, nr 2, s. 151-160Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The present study aimed to investigate motivations for the dual career of European student-athletes living in countries providing different educational services for elite athletes: State-centric regulation–State as sponsor/facilitator (State), National Sporting Federations/Institutes as intermediary (Federation) and Laisser Faire, no formal structures (No Structure). Therefore, the European Student-athletes’ Motivation towards Sports and Academics Questionnaire (SAMSAQ-EU) was administered to 524 European student-athletes. Exploratory Factor Analysis, and Confirmatory Factor Analysis were applied to test the factor structure, and the reliability and validity of the SAMSAQ-EU, respectively. A multivariate approach was applied to verify subgroup effects (P ≤ 0.05) according to gender (i.e., female and male), age (i.e., ≤24 years, >24 years), type of sport (i.e., individual sport and team sport) and competition level (i.e., national and international). Insufficient confirmatory indexes were reported for the whole European student-athlete group, whereas distinct three factor models [i.e., Student Athletic Motivation (SAM); Academic Motivation (AM); Career Athletic Motivation (CAM)] emerged, with acceptable reliability estimates, for State (SAM = 0.82; AM = 0.75; and CAM = 0.75), Federation (SAM = 0.82; AM = 0.66; and CAM = 0.87) and No Structure (SAM = 0.78; AM = 0.74; and CAM = 0.79) subgroups. Differences between subgroups were found only for competition level (P < 0.001) in relation to SAM (P = 0.001) and CAM (P < 0.001). For SAM, the highest and lowest values emerged for Federation (national, 5.1 ± 0.5; international, 5.4 ± 0.5) and State (national, 4.5 ± 0.9; international, 4.8 ± 0.7). The opposite picture emerged for CAM (Federation: national, 3.3 ± 0.7; international, 3.5 ± 0.9; State: national, 5.0 ± 0.8; international, 5.0 ± 0.9). Therefore, despite SAMSAQ-EU demonstrated to be a useful tool, results showed that European student-athletes’ motivation for dual career has to be specifically investigated according to social contexts.

  • 225. Lytsy, Per
    et al.
    Ingelsson, Erik
    Lind, Lars
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Sundström, Johan
    Interplay of overweight and insulin resistance on hypertension development2014Ingår i: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 32, nr 4, s. 834-839Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVES: Obesity and hypertension are associated, possibly through causal pathways involving insulin resistance and metabolic derangements. We aimed to investigate in a whites sample if overweight or obese persons without insulin resistance are at risk of developing hypertension or blood pressure progression.

    METHODS: In a meta-analysis, using multivariable-adjusted mixed-effects logistic regression models, we investigated the risks of hypertension development and blood pressure progression by combinations of relative weight classes and presence or absence of insulin resistance (defined as highest vs. lower three quartiles using the homeostatic model assessment method) in the Uppsala Longitudinal Study of Adult Men (n = 2322) and the Prospective Investigation of the Vasculature in Uppsala Seniors studies (n = 1066). These two samples, consisting mainly of middle-aged and elderly men, provided 1846 observations for the development of hypertension in normotensive individuals and 4223 observations for progressing to a higher blood pressure stage.

    RESULTS: During a median of 10 years of follow-up, 884 (47.9%) developed hypertension and 1639 (38.8%) progressed to a higher blood pressure stage. Overweight or obese persons without insulin resistance had an increased risk of hypertension development [odds ratio (OR) 1.46, 95% confidence interval 1.14-1.88] and blood pressure progression (OR 1.32, 1.10-1.59) compared with normal-weight persons without insulin resistance.

    CONCLUSION: According to this study, being overweight or obese without insulin resistance increases the risk of hypertension and blood pressure progression. This adds to the evidence that overweight and obesity may be harmful per se, and that overweight and obesity without glucometabolic derangements are not benign conditions.

  • 226.
    Löfbom, Linda
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Vidare i livet – inte tillbaka: Upplevelser av hur funktionsnedsättning och behandling påverkar livstillfredsställelsen hos vuxna personer med mjukdelssarkom.: En kvalitativ studie2018Självständigt arbete på avancerad nivå (magisterexamen), 10 poäng / 15 hpStudentuppsats (Examensarbete)
    Abstract [sv]

    Bakgrund: Mjukdelssarkom är en ovanlig cancerform som behandlas med kirurgi, strålbehandling och cytostatika. Dessa behandlingar kan orsaka funktionsnedsättning som påverkar livstillfredsställelsen hos individerna som drabbas. Livstillfredsställelse är den subjektiva upplevelsen av livskvalitet. Syfte: Beskriva hur livstillfredsställelsen påverkats av diagnos, behandling och funktionsnedsättning vid mjukdelssarkom. Metod: Kvalitativ ansats innefattande åtta semistrukturerade intervjuer. Intervjuerna transkriberades före analys med kvalitativ innehållsanalys. Resultat: Genom analysen framkom ett övergripande tema Vidare i livet. Temat omfattar kategorierna Reaktion vid diagnos, Upplevelse av behandling, Livet efter sjukdom och Må bra Slutsats: Besvär förekommer i vardagen men individerna begränsas inte av dem, de upplever ingen funktionsnedsättning. Livstillfredsställelsen var påverkad under behandlingen. Efter avslutad behandling det vill säga vid tidpunkt för intervjun ansåg forskningspersonerna att deras livstillfredsställelse inte var påverkad.

  • 227. Magnusson, Carl
    et al.
    Axelsson, Christer
    Nilsson, Lena
    Strömsöe, Anneli
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Munters, Monica
    Herlitz, Johan
    Andersson Hagiwara, Magnus
    The final assessment and its association with field assessment in patients who were transported by the emergency medical service2018Ingår i: Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine, ISSN 1757-7241, E-ISSN 1757-7241, Vol. 26, nr 1, artikel-id 111Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: In patients who call for the emergency medical service (EMS), there is a knowledge gap with regard to the final assessment after arriving at hospital and its association with field assessment.

    AIM: In a representative population of patients who call for the EMS, to describe a) the final assessment at hospital discharge and b) the association between the assessment in the field and the assessment at hospital discharge.

    METHODS: Thirty randomly selected patients reached by a dispatched ambulance each month between 1 Jan and 31 Dec 2016 in one urban, one rural and one mixed ambulance organisation in Sweden took part in the study. The exclusion criteria were age < 18 years, dead on arrival, transport between health-care facilities and secondary missions. Each patient received a unique code based on the ICD code at hospital discharge and field assessment.

    RESULTS: In all, 1080 patients took part in the study, of which 1076 (99.6%) had a field assessment code. A total of 894 patients (83%) were brought to a hospital and an ICD code (ICD-10-SE) was available in 814 patients (91% of these cases and 76% of all cases included in the study). According to these ICD codes, the most frequent conditions were infection (15%), trauma (15%) and vascular disease (9%). The most frequent body localisation of the condition was the thorax (24%), head (16%) and abdomen (13%). In 118 patients (14% of all ICD codes), the condition according to the ICD code was judged as time critical. Among these cases, field assessment was assessed as potentially appropriate in 75% and potentially inappropriate in 12%.

    CONCLUSION: Among patients reached by ambulance in Sweden, 83% were transported to hospital and, among them, 14% had a time-critical condition. In these cases, the majority were assessed in the field as potentially appropriate, but 12% had a potentially inappropriate field assessment. The consequences of these findings need to be further explored.

  • 228. Mahajan, Anubha
    et al.
    Rodan, Aylin R
    Le, Thu H
    Gaulton, Kyle J
    Haessler, Jeffrey
    Stilp, Adrienne M
    Kamatani, Yoichiro
    Zhu, Gu
    Sofer, Tamar
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Uppsala university.
    Trans-ethnic fine mapping highlights kidney-function genes linked to salt sensitivity2016Ingår i: American Journal of Human Genetics, ISSN 0002-9297, E-ISSN 1537-6605, Vol. 99, nr 3, s. 636-646Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We analyzed genome-wide association studies (GWASs), including data from 71,638 individuals from four ancestries, for estimated glomerular filtration rate (eGFR), a measure of kidney function used to define chronic kidney disease (CKD). We identified 20 loci attaining genome-wide-significant evidence of association (p < 5 × 10(-8)) with kidney function and highlighted that allelic effects on eGFR at lead SNPs are homogeneous across ancestries. We leveraged differences in the pattern of linkage disequilibrium between diverse populations to fine-map the 20 loci through construction of "credible sets" of variants driving eGFR association signals. Credible variants at the 20 eGFR loci were enriched for DNase I hypersensitivity sites (DHSs) in human kidney cells. DHS credible variants were expression quantitative trait loci for NFATC1 and RGS14 (at the SLC34A1 locus) in multiple tissues. Loss-of-function mutations in ancestral orthologs of both genes in Drosophila melanogaster were associated with altered sensitivity to salt stress. Renal mRNA expression of Nfatc1 and Rgs14 in a salt-sensitive mouse model was also reduced after exposure to a high-salt diet or induced CKD. Our study (1) demonstrates the utility of trans-ethnic fine mapping through integration of GWASs involving diverse populations with genomic annotation from relevant tissues to define molecular mechanisms by which association signals exert their effect and (2) suggests that salt sensitivity might be an important marker for biological processes that affect kidney function and CKD in humans.

  • 229. Malmström, H
    et al.
    Wändell, P E
    Holzmann, M J
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Uppsala universitet.
    Jungner, I
    Hammar, N
    Walldius, G
    Carlsson, A C
    Low fructosamine and mortality - A long term follow-up of 215,011 non-diabetic subjects in the Swedish AMORIS study2016Ingår i: NMCD. Nutrition Metabolism and Cardiovascular Diseases, ISSN 0939-4753, E-ISSN 1590-3729, Vol. 26, nr 12, s. 1120-1128Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND AND AIMS: Both high and low fasting glucose has been associated with an increased mortality among individuals without diabetes. This J-shaped association has also been shown for HbA1c in relation to all-cause mortality. High fructosamine is associated with increased mortality. In this study we aim to evaluate if low fructosamine is also associated with increased mortality in non-diabetic subjects.

    METHODS AND RESULTS: We included 215,011 subjects from the AMORIS cohort undergoing occupational health screening or primary care in Stockholm, Sweden. Cause specific mortality was obtained from the Swedish Cause-of-Death Register by record linkage. Hazard ratios for the lowest decile of fructosamine were estimated by Cox regression for all-cause (n = 41,388 deaths) and cause-specific mortality during 25 years of follow-up. We observed gradually increased mortality with lower fructosamine in a large segment of the population. In the lowest decile of fructosamine the sex, age, social class and calendar adjusted hazard ratio was 1.20 (95% CI; 1.18-1.27) compared to deciles 2-9. This increased mortality was attenuated after adjustment for six other biomarkers (HR = 1.11 (95% CI; 1.07-1.15)). Haptoglobin, an indicator of chronic inflammation, made the greatest difference in the point estimate. In sensitivity analyses we found an association between low fructosamine and smoking and adjustment for smoking further attenuated the association between low fructosamine and mortality.

    CONCLUSION: Low levels of fructosamine in individuals without diabetes were found to be associated with increased mortality. Smoking and chronic inflammation seem to at least partially explain this association but an independent contribution by low fructosamine cannot be excluded.

  • 230. Masterson, Siobhán
    et al.
    Strömsöe, Anneli
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Cullinan, John
    Deasy, Conor
    Vellinga, Akke
    Apples to apples: can differences in out-of-hospital cardiac arrest incidence and outcomes between Sweden and Ireland be explained by core Utstein variables?2018Ingår i: Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine, ISSN 1757-7241, E-ISSN 1757-7241, Vol. 26, nr 1, artikel-id 37Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Variation in reported incidence and outcome based on aggregated data is a persistent feature of out-of-hospital cardiac arrest (OHCA) epidemiology.

    OBJECTIVE: To investigate the extent to which patient-level analysis using core 'Utstein' variables explains inter-country variation between Sweden and the Republic of Ireland.

    METHODS: A retrospective cross-sectional comparative study was performed, including all Swedish and Irish OHCA cases attended by Emergency Medical Services (EMS-attended OHCA) where resuscitation was attempted from 1st January 2012 to 31st December 2014. Incidence rates per 100,000 population were adjusted for age and gender. Two subgroups were extracted: (1) Utstein - adult patients, bystander-witnessed collapse, presumed medical aetiology, initial shockable rhythm and (2) Emergency Medical Service (EMS)-witnessed events. Multivariable logistic regression analysis was used to identify predictors of survival following multiple imputations of data.

    RESULTS: Five thousand eight hundred eighty six Irish and 15,303 Swedish patients were included. Swedish patients were older than Irish patients (median age 71 vs. 66 years respectively). Adjusted incidence was significantly higher in Sweden compared to the Republic of Ireland (52.9 vs. 43.1 per 100,000 population per year). Proportionate survival in Sweden was greater for both subgroups and all age categories. Regression analysis of the Utstein subgroup predicted approximately 17% of variation in outcome, but there was a large unexplained 'country effect' for survival in favour of Sweden (OR 4.40 (95% CI 2.55-7.56)).

    CONCLUSIONS: Using patient level data, a proportion of inter-country variation was explained, but substantial variation was not explained by the core Utstein variables. Researchers and policy makers should be aware of the potential for unmeasured differences when comparing OHCA incidence and outcomes between countries.

  • 231. Matsushita, Kunihiro
    et al.
    Ballew, Shoshana H
    Coresh, Josef
    Arima, Hisatomi
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Uppsala universitet.
    Cirillo, Massimo
    Ebert, Natalie
    Hiramoto, Jade S
    Kimm, Heejin
    Kronenberg, Florian
    Measures of chronic kidney disease and risk of incident peripheral artery disease: a collaborative meta-analysis of individual participant data2017Ingår i: The Lancet Diabetes and Endocrinology, ISSN 2213-8587, E-ISSN 2213-8595, Vol. 5, nr 9, s. 718-728Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Some evidence suggests that chronic kidney disease is a risk factor for lower-extremity peripheral artery disease. We aimed to quantify the independent and joint associations of two measures of chronic kidney disease (estimated glomerular filtration rate [eGFR] and albuminuria) with the incidence of peripheral artery disease.

    METHODS: In this collaborative meta-analysis of international cohorts included in the Chronic Kidney Disease Prognosis Consortium (baseline measurements obtained between 1972 and 2014) with baseline measurements of eGFR and albuminuria, at least 1000 participants (this criterion not applied to cohorts exclusively enrolling patients with chronic kidney disease), and at least 50 peripheral artery disease events, we analysed adult participants without peripheral artery disease at baseline at the individual patient level with Cox proportional hazards models to quantify associations of creatinine-based eGFR, urine albumin-to-creatinine ratio (ACR), and dipstick proteinuria with the incidence of peripheral artery disease (including hospitalisation with a diagnosis of peripheral artery disease, intermittent claudication, leg revascularisation, and leg amputation). We assessed discrimination improvement through c-statistics.

    FINDINGS: We analysed 817 084 individuals without a history of peripheral artery disease at baseline from 21 cohorts. 18 261 cases of peripheral artery disease were recorded during follow-up across cohorts (median follow-up was 7·4 years [IQR 5·7-8·9], range 2·0-15·8 years across cohorts). Both chronic kidney disease measures were independently associated with the incidence of peripheral artery disease. Compared with an eGFR of 95 mL/min per 1·73 m(2), adjusted hazard ratios (HRs) for incident study-specific peripheral artery disease was 1·22 (95% CI 1·14-1·30) at an eGFR of 45 mL/min per 1·73 m(2) and 2·06 (1·70-2·48) at an eGFR of 15 mL/min per 1·73 m(2). Compared with an ACR of 5 mg/g, the adjusted HR for incident study-specific peripheral artery disease was 1·50 (1·41-1·59) at an ACR of 30 mg/g and 2·28 (2·12-2·44) at an ACR of 300 mg/g. The adjusted HR at an ACR of 300 mg/g versus 5 mg/g was 3·68 (95% CI 3·00-4·52) for leg amputation. eGFR and albuminuria contributed multiplicatively (eg, adjusted HR 5·76 [4·90-6·77] for incident peripheral artery disease and 10·61 [5·70-19·77] for amputation in eGFR <30 mL/min per 1·73 m(2) plus ACR ≥300 mg/g or dipstick proteinuria 2+ or higher vs eGFR ≥90 mL/min per 1·73 m(2) plus ACR <10 mg/g or dipstick proteinuria negative). Both eGFR and ACR significantly improved peripheral artery disease risk discrimination beyond traditional predictors, with a substantial improvement prediction of amputation with ACR (difference in c-statistic 0·058, 95% CI 0·045-0·070). Patterns were consistent across clinical subgroups.

    INTERPRETATION: Even mild-to-moderate chronic kidney disease conferred increased risk of incident peripheral artery disease, with a strong association between albuminuria and amputation. Clinical attention should be paid to the development of peripheral artery disease symptoms and signs in people with any stage of chronic kidney disease.

    FUNDING: American Heart Association, US National Kidney Foundation, and US National Institute of Diabetes and Digestive and Kidney Diseases.

  • 232. Matsushita, Kunihiro
    et al.
    Coresh, Josef
    Sang, Yingying
    Chalmers, John
    Fox, Caroline
    Guallar, Eliseo
    Jafar, Tazeen
    Jassal, Simerjot K.
    Landman, Gijs W. D.
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Estimated glomerular filtration rate and albuminuria for prediction of cardiovascular outcomes: a collaborative meta-analysis of individual participant data2015Ingår i: LANCET DIABETES & ENDOCRINOLOGY, ISSN 2213-8587, Vol. 3, nr 7, s. 514-525Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The usefulness of estimated glomerular filtration rate (eGFR) and albuminuria for prediction of cardiovascular outcomes is controversial. We aimed to assess the addition of creatinine-based eGFR and albuminuria to traditional risk factors for prediction of cardiovascular risk with a meta-analytic approach.

    Methods: We meta-analysed individual-level data for 637 315 individuals without a history of cardiovascular disease from 24 cohorts (median follow-up 4.2-19.0 years) included in the Chronic Kidney Disease Prognosis Consortium. We assessed C statistic difference and reclassification improvement for cardiovascular mortality and fatal and non-fatal cases of coronary heart disease, stroke, and heart failure in a 5 year timeframe, contrasting prediction models for traditional risk factors with and without creatinine-based eGFR, albuminuria (either albumin-to-creatinine ratio [ACR] or semi-quantitative dipstick proteinuria), or both.

    Findings: The addition of eGFR and ACR significantly improved the discrimination of cardiovascular outcomes beyond traditional risk factors in general populations, but the improvement was greater with ACR than with eGFR, and more evident for cardiovascular mortality (C statistic difference 0.0139 [95% CI 0.0105- 0.0174] for ACR and 0.0065 [0.0042-0.0088] for eGFR) and heart failure (0.0196 [0.0108-0.0284] and 0.0109 [0.0059-0.0159]) than for coronary disease (0.0048 [0.0029-0.0067] and 0.0036 [0.0019-0.0054]) and stroke (0.0105 [0.0058-0.0151]and 0.0036 [0.0004-0.0069]). Dipstick proteinuria showed smaller improvement than ACR. The discrimination improvement with eGFR or ACR was especially evident in individuals with diabetes or hypertension, but remained significant with ACR for cardiovascular mortality and heart failure in those without either of these disorders. In individuals with chronic kidney disease, the combination of eGFR and ACR for risk discrimination outperformed most single traditional predictors; the C statistic for cardiovascular mortality fell by 0.0227 (0.0158-0.0296) after omission of eGFR and ACR compared with less than 0.007 for any single modifiable traditional predictor.

    Interpretation: Creatinine-based eGFR and albuminuria should be taken into account for cardiovascular prediction, especially when these measures are already assessed for clinical purpose or if cardiovascular mortality and heart failure are outcomes of interest. ACR could have particularly broad implications for cardiovascular prediction. In populations with chronic kidney disease, the simultaneous assessment of eGFR and ACR could facilitate improved classification of cardiovascular risk, supporting current guidelines for chronic kidney disease. Our results lend some support to also incorporating eGFR and ACR into assessments of cardiovascular risk in the general population.

  • 233. Matsushita, Kunihiro
    et al.
    Mahmoodi, Bakhtawar K
    Woodward, Mark
    Emberson, Jonathan R
    Jafar, Tazeen H
    Jee, Sun Ha
    Polkinghorne, Kevan R
    Shankar, Anoop
    Smith, David H
    Tonelli, Marcello
    Warnock, David G
    Wen, Chi-Pang
    Coresh, Josef
    Gansevoort, Ron T
    Hemmelgarn, Brenda R
    Levey, Andrew S
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Comparison of risk prediction using the CKD-EPI equation and the MDRD study equation for estimated glomerular filtration rate2012Ingår i: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 307, nr 18, s. 1941-51Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    CONTEXT: The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation more accurately estimates glomerular filtration rate (GFR) than the Modification of Diet in Renal Disease (MDRD) Study equation using the same variables, especially at higher GFR, but definitive evidence of its risk implications in diverse settings is lacking.

    OBJECTIVE: To evaluate risk implications of estimated GFR using the CKD-EPI equation compared with the MDRD Study equation in populations with a broad range of demographic and clinical characteristics.

    DESIGN, SETTING, AND PARTICIPANTS: A meta-analysis of data from 1.1 million adults (aged ≥ 18 years) from 25 general population cohorts, 7 high-risk cohorts (of vascular disease), and 13 CKD cohorts. Data transfer and analyses were conducted between March 2011 and March 2012.

    MAIN OUTCOME MEASURES: All-cause mortality (84,482 deaths from 40 cohorts), cardiovascular mortality (22,176 events from 28 cohorts), and end-stage renal disease (ESRD) (7644 events from 21 cohorts) during 9.4 million person-years of follow-up; the median of mean follow-up time across cohorts was 7.4 years (interquartile range, 4.2-10.5 years).

    RESULTS: Estimated GFR was classified into 6 categories (≥90, 60-89, 45-59, 30-44, 15-29, and <15 mL/min/1.73 m(2)) by both equations. Compared with the MDRD Study equation, 24.4% and 0.6% of participants from general population cohorts were reclassified to a higher and lower estimated GFR category, respectively, by the CKD-EPI equation, and the prevalence of CKD stages 3 to 5 (estimated GFR <60 mL/min/1.73 m(2)) was reduced from 8.7% to 6.3%. In estimated GFR of 45 to 59 mL/min/1.73 m(2) by the MDRD Study equation, 34.7% of participants were reclassified to estimated GFR of 60 to 89 mL/min/1.73 m(2) by the CKD-EPI equation and had lower incidence rates (per 1000 person-years) for the outcomes of interest (9.9 vs 34.5 for all-cause mortality, 2.7 vs 13.0 for cardiovascular mortality, and 0.5 vs 0.8 for ESRD) compared with those not reclassified. The corresponding adjusted hazard ratios were 0.80 (95% CI, 0.74-0.86) for all-cause mortality, 0.73 (95% CI, 0.65-0.82) for cardiovascular mortality, and 0.49 (95% CI, 0.27-0.88) for ESRD. Similar findings were observed in other estimated GFR categories by the MDRD Study equation. Net reclassification improvement based on estimated GFR categories was significantly positive for all outcomes (range, 0.06-0.13; all P < .001). Net reclassification improvement was similarly positive in most subgroups defined by age (<65 years and ≥65 years), sex, race/ethnicity (white, Asian, and black), and presence or absence of diabetes and hypertension. The results in the high-risk and CKD cohorts were largely consistent with the general population cohorts.

    CONCLUSION: The CKD-EPI equation classified fewer individuals as having CKD and more accurately categorized the risk for mortality and ESRD than did the MDRD Study equation across a broad range of populations.

  • 234. Melhus, H
    et al.
    Snellman, G
    Gedeborg, R
    Byberg, L
    Berglund, L
    Mallmin, H
    Hellman, P
    Blomhoff, R
    Hagström, E
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Michaelsson, K
    Plasma 25-Hydroxyvitamin D levels and fracture risk in a community-based cohort of elderly men in Sweden2010Ingår i: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 95, nr 6, s. 2637-2645Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Context: Blood levels of 25-hydroxyvitamin D [25(OH)D] is the generally accepted indicator of vitamin D status, but no universal reference level has been reached.

    Objective: The objective of the study was to determine the threshold at which low plasma 25(OH)D levels are associated with fractures in elderly men and clarify the importance of low levels on total fracture burden. Design and

    Participants: In the Uppsala Longitudinal Study of Adult Men, a population-based cohort (mean age, 71 yr, n = 1194), we examined the relationship between 25(OH)D and risk for fracture. Plasma 25(OH)D levels were measured with high-pressure liquid chromatography-mass spectrometry. Setting: The study was conducted in the municipality of Uppsala in Sweden, a country with a high fracture incidence.

    Main Outcome Measure: Time to fracture was measured. Results: During follow-up (median 11 yr), 309 of the participants (26%) sustained a fracture. 25(OH)D levels below 40 nmol/liter, which corresponded to the fifth percentile of 25(OH)D, were associated with a modestly increased risk for fracture, multivariable-adjusted hazard ratio 1.65 (95% confidence interval 1.09–2.49). No risk difference was detected above this level. Approximately 3% of the fractures were attributable to low 25(OH)D levels in this population.

    Conclusions: Vitamin D insufficiency is not a major cause of fractures in community-dwelling elderly men in Sweden. Despite the fact that cutaneous synthesis of previtamin D during the winter season is undetectable at this northern latitude of 60°, only one in 20 had 25(OH)D levels below 40 nmol/liter, the threshold at which the risk for fracture started to increase. Genetic adaptations to limited UV light may be an explanation for our findings.

  • 235. Michaelsson, K
    et al.
    Baron, JA
    Snellman, G
    Gedeborg, R
    Byberg, L
    Sundström, J
    Berglund, L
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Hellman, P
    Blomhoff, R
    Wolk, A
    Garmo, H
    Holmberg, L
    Melhus, H
    Plasma vitamin D and mortality in older men: a community-based prospective cohort study2010Ingår i: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 92, nr 4, s. 841-848Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Vitamin D status is known to be important for bone health but may also affect the development of several chronic diseases, including cancer and cardiovascular diseases, which are 2 major causes of death.

    Objective: We aimed to examine how vitamin D status relates to overall and cause-specific mortality. Design: The Uppsala Longitudinal Study of Adult Men, a community-based cohort of elderly men (mean age at baseline: 71 y; n = 1194), was used to investigate the association between plasma 25-hydroxyvitamin D [25(OH)D] and mortality. Total plasma 25(OH)D was determined with HPLC atmospheric pressure chemical ionization mass spectrometry. Proportional hazards regression was used to compute hazard ratios (HRs).

    Results: During follow-up (median: 12.7 y), 584 (49%) participants died. There was a U-shaped association between vitamin D concentrations and total mortality. An approximately 50% higher total mortality rate was observed among men in the lowest 10% (<46 nmol/L) and the highest 5% (>98 nmol/L) of plasma 25(OH)D concentrations compared with intermediate concentrations. Cancer mortality was also higher at low plasma concentrations (multivariable-adjusted HR: 2.20; 95% CI: 1.44, 3.38) and at high concentrations (HR: 2.64; 95% CI: 1.46, 4.78). For cardiovascular death, only low (HR: 1.89; 95% CI: 1.21, 2.96) but not high (HR: 1.33; 95% CI: 0.69, 2.54) concentrations indicated higher risk.

    Conclusions: Both high and low concentrations of plasma 25(OH)D are associated with elevated risks of overall and cancer mortality. Low concentrations are associated with cardiovascular mortality.

  • 236. Michaëlsson, Karl
    et al.
    Wolk, Alicja
    Byberg, Liisa
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Melhus, Håkan
    Intake and serum concentrations of α-tocopherol in relation to fractures in elderly women and men: 2 cohort studies2014Ingår i: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 99, nr 1, s. 107-114Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: A reduction in the formation of free radicals and oxidative stress might reduce the rate of bone loss and muscle wasting.

    OBJECTIVE: The objective was to determine whether α-tocopherol intake or serum concentrations are associated with fracture risk in older women and men.

    DESIGN: Two cohort studies, the Swedish Mammography Cohort (SMC; n = 61,433 women) and the Uppsala Longitudinal Study of Adult Men (ULSAM; n = 1138 men), were used.

    RESULTS: During 19 y of follow-up, 14,738 women in the SMC experienced a first fracture at any site (3871 hip fractures). A higher hip fracture rate was observed with lower intakes of α-tocopherol. Compared with the highest quintile of intake, the lowest quintile had a multivariable-adjusted HR of 1.86 (95% CI: 1.67, 2.06). The HR of any fracture was 1.20 (95% CI: 1.14, 1.28). α-Tocopherol-containing supplement use was associated with a reduced rate of hip fracture (HR: 0.78; 95% CI: 0.65, 0.93) and any fracture (HR: 0.86; 95% CI: 0.78, 0.94). Compared with the highest quintile of α-tocopherol intake in ULSAM (follow-up: 12 y), lower intakes (quintiles 1-4) were associated with a higher rate of hip fracture (HR: 3.33; 95% CI: 1.43, 7.76) and any fracture (HR: 1.84; 95% CI: 1.18, 2.88). The HR for hip fracture in men for each 1-SD decrease in serum α-tocopherol was 1.58 (95% CI: 1.13, 2.22) and for any fracture was 1.23 (95% CI: 1.02, 1.48).

    CONCLUSION: Low intakes and low serum concentrations of α-tocopherol are associated with an increased rate of fracture in elderly women and men.

  • 237. Mok, Yejin
    et al.
    Ballew, Shoshana H
    Sang, Yingying
    Grams, Morgan E
    Coresh, Josef
    Evans, Marie
    Barany, Peter
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Karolinska institutet.
    Carrero, Juan-Jesus
    Matsushita, Kunihiro
    Albuminuria as a predictor of cardiovascular outcomes in patients with acute myocardial infarction2019Ingår i: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 8, nr 8, artikel-id e010546Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background. In patients with myocardial infarction ( MI ), reduced kidney function is recognized as an important predictor of poor prognosis, but the impact of albuminuria, a representative measure of kidney damage, has not been extensively evaluated.

    Methods and Results. In the SCREAM (Stockholm Creatinine Measurements) project (2006-2012), we identified 2469 patients with incident MI with dipstick proteinuria measured within a year before MI (427 patients also had urine albumin to creatinine ratio [ ACR ] measured concurrently) and obtained estimates for ACR with multiple imputation in participants with data solely on dipstick proteinuria. We quantified the association of ACR with the post- MI composite and individual outcomes of all-cause mortality, cardiovascular mortality, recurrent MI , ischemic stroke, or heart failure using Cox models and then evaluated the improvement in C statistic. During a median follow-up of 1.0 year after MI , 1607 participants (65.1%) developed the post- MI composite outcome. Higher ACR levels were independently associated with all outcomes except for ischemic stroke. Per 8-fold higher ACR (eg, 40 versus 5 mg/g), the hazard ratio of composite outcome was 1.21 (95% CI , 1.08-1.35). The addition of the ACR improved the C statistic of the post- MI composite by 0.040 (95% CI, 0.030-0.051). Largely similar results were obtained regardless of diabetic status and when ACR or dipstick was separately analyzed without imputation.

    Conclusions. In patients with MI , albuminuria was a potent predictor of subsequent outcomes, suggesting the importance of paying attention to the information on albuminuria, in addition to kidney function, in this high-risk population.

  • 238. Mokdad, Ali
    et al.
    Azzopardi, Peter
    Cini, Karly
    Kennedy, Elissa
    Sawyer, Susan
    El Bcheraoui, Charbel
    Charara, Raghid
    Khalil, Ibrahim
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Karolinska institutet.
    Murray, Christopher J. L
    Adolescent health in the Eastern Mediterranean Region: findings from the global burden of disease 2015 study2018Ingår i: International Journal of Public Health, ISSN 1661-8556, E-ISSN 1661-8564, Vol. 63, nr S1, s. 79-96Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The 22 countries of the East Mediterranean Region (EMR) have large populations of adolescents aged 10-24 years. These adolescents are central to assuring the health, development, and peace of this region. We described their health needs. Using data from the Global Burden of Disease Study 2015 (GBD 2015), we report the leading causes of mortality and morbidity for adolescents in the EMR from 1990 to 2015. We also report the prevalence of key health risk behaviors and determinants. Communicable diseases and the health consequences of natural disasters reduced substantially between 1990 and 2015. However, these gains have largely been offset by the health impacts of war and the emergence of non-communicable diseases (including mental health disorders), unintentional injury, and self-harm. Tobacco smoking and high body mass were common health risks amongst adolescents. Additionally, many EMR countries had high rates of adolescent pregnancy and unmet need for contraception. Even with the return of peace and security, adolescents will have a persisting poor health profile that will pose a barrier to socioeconomic growth and development of the EMR

  • 239. Mokdad, Ali
    et al.
    El Bcheraoui, Charbel
    Afshin, Ashkan
    Charara, Raghid
    Khalil, Ibrahim
    Moradi-Lakeh, Maziar
    Kassebaum, Nicholas
    Collison, Michael
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Karolinska institutet.
    Murray, Christopher
    Burden of obesity in the Eastern Mediterranean Region: findings from the Global Burden of Disease 2015 study2018Ingår i: International Journal of Public Health, ISSN 1661-8556, E-ISSN 1661-8564, Vol. 63, nr S1, s. 165-176Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We used the Global Burden of Disease (GBD) 2015 study results to explore the burden of high body mass index (BMI) in the Eastern Mediterranean Region (EMR). We estimated the prevalence of overweight and obesity among children (2-19 years) and adults (20 years) in 1980 and 2015. The burden of disease related to high BMI was calculated using the GBD comparative risk assessment approach. The prevalence of obesity increased for adults from 15.1% (95% UI 13.4-16.9) in 1980 to 20.7% (95% UI 18.8-22.8) in 2015. It increased from 4.1% (95% UI 2.9-5.5) to 4.9% (95% UI 3.6-6.4) for the same period among children. In 2015, there were 417,115 deaths and 14,448,548 disability-adjusted life years (DALYs) attributable to high BMI in EMR, which constitute about 10 and 6.3% of total deaths and DALYs, respectively, for all ages. This is the first study to estimate trends in obesity burden for the EMR from 1980 to 2015. We call for EMR countries to invest more resources in prevention and health promotion efforts to reduce this burden.

  • 240. Mokdad, Ali
    et al.
    Khalil, Ibrahim
    Collison, Michael
    El Bcheraoui, Charbel
    Charara, Raghid
    Moradi-Lakeh, Maziar
    Afshin, Ashkan
    Krohn, Kristopher
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Karolinska institutet.
    Murray, Christopher
    Neonatal, infant, and under-5 mortality and morbidity burden in the Eastern Mediterranean region: findings from the Global Burden of Disease 2015 study2018Ingår i: International Journal of Public Health, ISSN 1661-8556, E-ISSN 1661-8564, Vol. 63, nr S1, s. 63-77Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Although substantial reductions in under-5 mortality have been observed during the past 35 years, progress in the Eastern Mediterranean Region (EMR) has been uneven. This paper provides an overview of child mortality and morbidity in the EMR based on the Global Burden of Disease (GBD) study. We used GBD 2015 study results to explore under-5 mortality and morbidity in EMR countries. In 2015, 755,844 (95% uncertainty interval (UI) 712,064-801,565) children under 5 died in the EMR. In the early neonatal category, deaths in the EMR decreased by 22.4%, compared to 42.4% globally. The rate of years of life lost per 100,000 population under 5 decreased 54.38% from 177,537 (173,812-181,463) in 1990 to 80,985 (76,308-85,876) in 2015; the rate of years lived with disability decreased by 0.57% in the EMR compared to 9.97% globally. Our findings call for accelerated action to decrease child morbidity and mortality in the EMR. Governments and organizations should coordinate efforts to address this burden. Political commitment is needed to ensure that child health receives the resources needed to end preventable deaths.

  • 241. Mokdad, Ali
    et al.
    Moradi-Lekeh, Maziar
    El Bcheraoui, Charbel
    Khalil, Ibrahim
    Charara, Raghid
    Afshin, Ashkan
    Wang, Haidong
    Collison, Michael
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Karolinska institutet.
    Murray, Christopher
    Diabetes mellitus and chronic kidney disease in the Eastern Mediterranean Region: findings from the Global Burden of Disease 2015 study2018Ingår i: International Journal of Public Health, ISSN 1661-8556, E-ISSN 1661-8564, Vol. 63, nr S1, s. 177-186Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We used findings from the Global Burden of Disease 2015 study to update our previous publication on the burden of diabetes and chronic kidney disease due to diabetes (CKD-DM) during 1990-2015. We extracted GBD 2015 estimates for prevalence, mortality, and disability-adjusted life years (DALYs) of diabetes (including burden of low vision due to diabetes, neuropathy, and amputations and CKD-DM for 22 countries of the EMR from the GBD visualization tools. In 2015, 135,230 (95% UI 123,034-148,184) individuals died from diabetes and 16,470 (95% UI 13,977-18,961) from CKD-DM, 216 and 179% increases, respectively, compared to 1990. The total number of people with diabetes was 42.3 million (95% UI 38.6-46.4 million) in 2015. DALY rates of diabetes in 2015 were significantly higher than the expected rates based on Socio-demographic Index (SDI). Our study showed a large and increasing burden of diabetes in the region. There is an urgency in dealing with diabetes and its consequences, and these efforts should be at the forefront of health prevention and promotion.

  • 242. Mokdad, Ali
    et al.
    Tehrani-Banihashemi, Arash
    Moradi-Lakeh, Maziar
    El Bcheraoui, Charbel
    Charara, Raghid
    Afshin, Ashkan
    Collison, Michael
    Daoud, Farah
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Karolinska institutet.
    Murray, Christopher
    Burden of cardiovascular diseases in the Eastern Mediterranean Region, 1990-2015: findings from the Global Burden of Disease 2015 study2018Ingår i: International Journal of Public Health, ISSN 1661-8556, E-ISSN 1661-8564, Vol. 63, nr S1, s. 137-149Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    To report the burden of cardiovascular diseases (CVD) in the Eastern Mediterranean Region (EMR) during 1990-2015. We used the 2015 Global Burden of Disease study for estimates of mortality and disability-adjusted life years (DALYs) of different CVD in 22 countries of EMR. A total of 1.4 million CVD deaths (95% UI: 1.3-1.5) occurred in 2015 in the EMR, with the highest number of deaths in Pakistan (465,116) and the lowest number of deaths in Qatar (723). The age-standardized DALY rate per 100,000 decreased from 10,080 in 1990 to 8606 in 2015 (14.6% decrease). Afghanistan had the highest age-standardized DALY rate of CVD in both 1990 and 2015. Kuwait and Qatar had the lowest age-standardized DALY rates of CVD in 1990 and 2015, respectively. High blood pressure, high total cholesterol, and high body mass index were the leading risk factors for CVD. The age-standardized DALY rates in the EMR are considerably higher than the global average. These findings call for a comprehensive approach to prevent and control the burden of CVD in the region.

  • 243. Molander, P.
    et al.
    Dong, H. -J
    Äng, Björn
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Karolinska institutet.
    Enthoven, P.
    Gerdle, B.
    The role of pain in chronic pain patients' perception of health-related quality of life: A cross-sectional SQRP study of 40,000 patients2018Ingår i: Scandinavian Journal of Pain, ISSN 1877-8860, E-ISSN 1877-8879, Vol. 18, nr 3Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Health-related quality of life (Hr-QoL) reflects the burden of a condition on an overarching level. Pain intensity, disability and other factors influence how patients with chronic pain perceive their condition, e.g. Hr-QoL. However, the relative importance of these factors is unclear and there is an ongoing debate as to what importance pain measures have in this group. We investigated the importance of current pain level and mood on aspects of Hr-QoL in patients with chronic pain and investigated whether such relationships are influenced by demographics. Data was obtained from the Swedish Quality Registry for Pain Rehabilitation (SQRP), between 2008 and 2016 on patients ≥18 years old who suffered from chronic pain and were referred to participating specialist clinics. Dependent variables were general Hr-QoL [using two scales from European Quality of Life instrument: EQ5D Index and the European Quality of Life instrument health scale (EQ thermometer)] and specific Hr-QoL [from the Short Form Health Survey (SF36) the physical component summary (SF36-PCS) and the mental (psychological) component summary (SF36-MCS)]. Independent variables were sociodemographic variables, pain variables, psychological distress and pain attitudes. Principal component analysis (PCA) was used for multivariate correlation analyses of all investigated variables and Orthogonal Partial Least Square Regression (OPLS) for multivariate regressions on health aspects. There was 40,518 patients (72% women). Pain intensity and interference showed the strongest multivariate correlations with EQ5D Index, EQ thermometer and SF36-PCS. Psychological distress variables displayed the strongest multivariate correlations with SF36-MCS. Demographic properties did not significantly influence variations in the investigated Hr-QoL variables. Pain, mood and pain attitudes were significantly correlated with Hr-QoL variables, but these variables cannot explain most of variations in Hr-QoL variables. The results pinpoint that broad assessments (including pain intensity aspects) are needed to capture the clinical presentation of patients with complex chronic pain conditions.

  • 244. Monnier, Andreas
    et al.
    Larsson, Helena
    Nero, Håkan
    Djupsjöbacka, Mats
    Äng, Björn
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Karolinska institutet; Uppsala universitet.
    A longitudinal observational study of back pain incidence, risk factors and occupational physical activity in Swedish marine trainees2019Ingår i: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 9, nr 5, artikel-id e025150Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVES: To evaluate the occurrence of low back pain (LBP) and LBP that limits work ability, to identify their potential early risks and to quantify occupational physical activity in Swedish Armed Forces (SwAF) marines during their basic 4 month marine training course.

    DESIGN: Prospective observational cohort study with weekly follow-ups.

    PARTICIPANTS: Fifty-three SwAF marines entering the training course.

    OUTCOMES: Incident of LBP and its related effect on work-ability and associated early risks. Occupational physical activity, as monitored using accelerometers and self-reports.

    RESULTS: During the training course, 68% of the marines experienced at least one episode of LBP. This yielded a LBP and LBP limiting work ability incidence rate of 13.5 (95% CI 10.4 to 17.8) and 6.3 (95% CI 4.2 to 10.0) episodes per 1000 person-days, respectively. Previous back pain and shorter body height (≤1.80 m) emerged as independent risks for LBP (HR 2.5, 95% CI 1.4 to 4.3; HR 2.0, 95% CI 1.2 to 3.3, respectively), as well as for LBP that limited work ability (HR 3.6, 95% CI 1.4 to 8.9; HR 4.5, 95% CI 2.0 to 10.0, respectively). Furthermore, managing fewer than four pull-ups emerged as a risk for LBP (HR 1.9, 95% CI 1.2 to 3.0), while physical training of fewer than three sessions per week emerged as a risk for LBP that limited work ability (HR 3.0, 95% CI 1.2 to 7.4). More than 80% of the work time measured was spent performing low levels of ambulation, however, combat equipment (≥17.5 kg) was carried for more than half of the work time.

    CONCLUSIONS: Incidents of LBP are common in SwAF marines' early careers. The link between LBP and previous pain as well as low levels of exercise highlights the need for preventive actions early on in a marine's career. The role of body height on LBP needs further investigation, including its relationship with body-worn equipment, before it can effectively contribute to LBP prevention.

  • 245. Moreno Velásquez, Ilais
    et al.
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Uppsala universitet.
    Leander, Karin
    Lind, Lars
    Gigante, Bruna
    Carlsson, Axel C
    Interleukin-8 is associated with increased total mortality in women but not in men-findings from a community-based cohort of elderly.2015Ingår i: Annals of Medicine, ISSN 0785-3890, E-ISSN 1365-2060, Vol. 47, nr 1, s. 28-33Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective. To elucidate the association among circulating IL-8 and total mortality in a cohort of elderly, and to explore potential sex differences in the observed association. Methods. The Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) is a cohort of 70-year-old men and women living in Uppsala, Sweden; baseline period: 2001-2004. IL-8 serum measurements were performed in 1003 participants. Results. In total, 61 men and 40 women died during follow-up (median 7.9 years). Baseline IL-8 concentrations were higher in women than in men (P = 0.03). In a multivariable model adjusting for age, established cardiovascular risk factors, and C-reactive protein, log-transformed standard deviation increments in IL-8 levels were weakly associated with an increased risk for total mortality (hazard ratio (HR) 1.12, 95% confidence interval (CI) 1.02-1.23, P < 0.05) in the whole cohort. Stratified analysis revealed an association in women (HR 1.18, 95% CI 1.06-1.30, P < 0.01) but not in men (HR 0.98, 95% CI 0.76-1.26). Conclusions. A weak association between IL-8 serum levels and an increased risk for mortality was observed. The prospective data support the role of IL-8 as a biomarker of interest; yet, further studies are warranted to elucidate validity of our finding and the possibility of a sex difference.

  • 246. Morris, Andrew P
    et al.
    Le, Thu H
    Wu, Haojia
    Akbarov, Artur
    van der Most, Peter J
    Hemani, Gibran
    Smith, George Davey
    Mahajan, Anubha
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Franceshini, N
    Trans-ethnic kidney function association study reveals putative causal genes and effects on kidney-specific disease aetiologies2019Ingår i: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 10, nr 1, artikel-id 29Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Chronic kidney disease (CKD) affects ~10% of the global population, with considerable ethnic differences in prevalence and aetiology. We assemble genome-wide association studies of estimated glomerular filtration rate (eGFR), a measure of kidney function that defines CKD, in 312,468 individuals of diverse ancestry. We identify 127 distinct association signals with homogeneous effects on eGFR across ancestries and enrichment in genomic annotations including kidney-specific histone modifications. Fine-mapping reveals 40 high-confidence variants driving eGFR associations and highlights putative causal genes with cell-type specific expression in glomerulus, and in proximal and distal nephron. Mendelian randomisation supports causal effects of eGFR on overall and cause-specific CKD, kidney stone formation, diastolic blood pressure and hypertension. These results define novel molecular mechanisms and putative causal genes for eGFR, offering insight into clinical outcomes and routes to CKD treatment development.

  • 247. Murray, Christopher J. L
    et al.
    Barber, Ryan M
    Foreman, Kyle J
    Ozgoren, Ayse Abbasoglu
    Abd-Allah, Foad
    Abera, Semaw F
    Aboyans, Victor
    Abraham, Jerry P
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Vos, heo
    Global, regional, and national disability-adjusted life years (DALYs) for 306 diseases and injuries and healthy life expectancy (HALE) for 188 countries, 1990-2013: quantifying the epidemiological transition2015Ingår i: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 386, nr 10009, s. 2145-2191Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: The Global Burden of Disease Study 2013 (GBD 2013) aims to bring together all available epidemiological data using a coherent measurement framework, standardised estimation methods, and transparent data sources to enable comparisons of health loss over time and across causes, age-sex groups, and countries. The GBD can be used to generate summary measures such as disability-adjusted life-years (DALYs) and healthy life expectancy (HALE) that make possible comparative assessments of broad epidemiological patterns across countries and time. These summary measures can also be used to quantify the component of variation in epidemiology that is related to sociodemographic development.

    METHODS: We used the published GBD 2013 data for age-specific mortality, years of life lost due to premature mortality (YLLs), and years lived with disability (YLDs) to calculate DALYs and HALE for 1990, 1995, 2000, 2005, 2010, and 2013 for 188 countries. We calculated HALE using the Sullivan method; 95% uncertainty intervals (UIs) represent uncertainty in age-specific death rates and YLDs per person for each country, age, sex, and year. We estimated DALYs for 306 causes for each country as the sum of YLLs and YLDs; 95% UIs represent uncertainty in YLL and YLD rates. We quantified patterns of the epidemiological transition with a composite indicator of sociodemographic status, which we constructed from income per person, average years of schooling after age 15 years, and the total fertility rate and mean age of the population. We applied hierarchical regression to DALY rates by cause across countries to decompose variance related to the sociodemographic status variable, country, and time.

    FINDINGS: Worldwide, from 1990 to 2013, life expectancy at birth rose by 6·2 years (95% UI 5·6-6·6), from 65·3 years (65·0-65·6) in 1990 to 71·5 years (71·0-71·9) in 2013, HALE at birth rose by 5·4 years (4·9-5·8), from 56·9 years (54·5-59·1) to 62·3 years (59·7-64·8), total DALYs fell by 3·6% (0·3-7·4), and age-standardised DALY rates per 100 000 people fell by 26·7% (24·6-29·1). For communicable, maternal, neonatal, and nutritional disorders, global DALY numbers, crude rates, and age-standardised rates have all declined between 1990 and 2013, whereas for non-communicable diseases, global DALYs have been increasing, DALY rates have remained nearly constant, and age-standardised DALY rates declined during the same period. From 2005 to 2013, the number of DALYs increased for most specific non-communicable diseases, including cardiovascular diseases and neoplasms, in addition to dengue, food-borne trematodes, and leishmaniasis; DALYs decreased for nearly all other causes. By 2013, the five leading causes of DALYs were ischaemic heart disease, lower respiratory infections, cerebrovascular disease, low back and neck pain, and road injuries. Sociodemographic status explained more than 50% of the variance between countries and over time for diarrhoea, lower respiratory infections, and other common infectious diseases; maternal disorders; neonatal disorders; nutritional deficiencies; other communicable, maternal, neonatal, and nutritional diseases; musculoskeletal disorders; and other non-communicable diseases. However, sociodemographic status explained less than 10% of the variance in DALY rates for cardiovascular diseases; chronic respiratory diseases; cirrhosis; diabetes, urogenital, blood, and endocrine diseases; unintentional injuries; and self-harm and interpersonal violence. Predictably, increased sociodemographic status was associated with a shift in burden from YLLs to YLDs, driven by declines in YLLs and increases in YLDs from musculoskeletal disorders, neurological disorders, and mental and substance use disorders. In most country-specific estimates, the increase in life expectancy was greater than that in HALE. Leading causes of DALYs are highly variable across countries.

    INTERPRETATION: Global health is improving. Population growth and ageing have driven up numbers of DALYs, but crude rates have remained relatively constant, showing that progress in health does not mean fewer demands on health systems. The notion of an epidemiological transition--in which increasing sociodemographic status brings structured change in disease burden--is useful, but there is tremendous variation in burden of disease that is not associated with sociodemographic status. This further underscores the need for country-specific assessments of DALYs and HALE to appropriately inform health policy decisions and attendant actions.

    FUNDING: Bill & Melinda Gates Foundation.

  • 248. Murray, Christopher J. L
    et al.
    Callender, Charlton
    Kulikoff, Xie Rachel
    Srinivasan, Vinay
    Abate, Degu
    Abate, Kalkidan Hassen
    Abay, Solomon
    Abbasi, Nooshin
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Karolinska institutet.
    Lim, Stephen S
    Population and fertility by age and sex for 195 countries and territories, 1950-2017: 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. 51-2015Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background Population estimates underpin demographic and epidemiological research and are used to track progress on numerous international indicators of health and development. To date, internationally available estimates of population and fertility, although useful, have not been produced with transparent and replicable methods and do not use standardised estimates of mortality. We present single-calendar year and single-year of age estimates of fertility and population by sex with standardised and replicable methods. 

    Methods We estimated population in 195 locations by single year of age and single calendar year from 1950 to 2017 with standardised and replicable methods. We based the estimates on the demographic balancing equation, with inputs of fertility, mortality, population, and migration data. Fertility data came from 7817 location-years of vital registration data, 429 surveys reporting complete birth histories, and 977 surveys and censuses reporting summary birth histories. We estimated age-specific fertility rates (ASFRs; the annual number of livebirths to women of a specified age group per 1000 women in that age group) by use of spatiotemporal Gaussian process regression and used the ASFRs to estimate total fertility rates (TFRs; the average number of children a woman would bear if she survived through the end of the reproductive age span [age 10-54 years] and experienced at each age a particular set of ASFRs observed in the year of interest). Because of sparse data, fertility at ages 10-14 years and 50-54 years was estimated from data on fertility in women aged 15-19 years and 45-49 years, through use of linear regression. Age-specific mortality data came from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 estimates. Data on population came from 1257 censuses and 761 population registry location-years and were adjusted for underenumeration and age misreporting with standard demographic methods. Migration was estimated with the GBD Bayesian demographic balancing model, after incorporating information about refugee migration into the model prior. Final population estimates used the cohort-cotnponent method of population projection, with inputs of fertility, mortality, and migration data. Population uncertainty was estimated by use of out-of-sample predictive validity testing. With these data, we estimated the trends in population by age and sex and in fertility by age between 1950 and 2017 in 195 countries and territories. 

    Findings From 1950 to 2017, TFRs decreased by 49.4% (95% uncertainty interval [UI] 46.4-52.0). The TFR decreased from 4.7 livebirths (4.5-4.9) to 2.4 livebirths (2.2-2.5), and the ASFR of mothers aged 10-19 years decreased from 37 livebirths (34-40) to 22 livebirths (19-24) per 1000 women. Despite reductions in the TFR, the global population has been increasing by an average of 83.8 million people per year since 1985. The global population increased by 197-2% (193.3-200.8) since 1950, from 2.6 billion (2.5-2.6) to 7.6 billion (7.4-7.9) people in 2017; much of this increase was in the proportion of the global population in south Asia and sub-Saharan Africa. The global annual rate of population growth increased between 1950 and 1964, when it peaked at 2.0%; this rate then remained nearly constant until 1970 and then decreased to 1.1% in 2017. Population growth rates in the southeast Asia, east Asia, and Oceania GBD super-region decreased from 2.5% in 1963 to O7% in 2017, whereas in sub-Saharan Africa, population growth rates were almost at the highest reported levels ever in 2017, when they were at 2.7%. The global average age increased from 26.6 years in 1950 to 32.1 years in 2017, and the proportion of the population that is of working age (age 15-64 years) increased from 59.9% to 65.3%. At the national level, the TFR decreased in all countries and territories between 1950 and 2017; in 2017, TFRs ranged from a low of 1.0 livebirths (95% UI 0. 9-1.2) in Cyprus to a high of 7.1 livebirths (6.8-7.4) in Niger. The TFR under age 25 years (TFU25; number of livebirths expected by age 25 years for a hypothetical woman who survived the age group and was exposed to current ASFRs) in 2017 ranged from 0.08 livebirths (0.07-0.09) in South Korea to 2.4 livebirths (2.2-2.6) in Niger, and the TFR over age 30 years (I F030; number of livebirths expected for a hypothetical woman ageing from 30 to 54 years who survived the age group and was exposed to current ASFRs) ranged from a low of 0.3 livebirths (0.3-0-4) in Puerto Rico to a high of 3.1 livebirths (3.0-3.2) in Niger. TF030 was higher than TFU25 in 145 countries and territories in 2017.33 countries had a negative population growth rate from 2010 to 2017, most of which were located in central, eastern, and western Europe, whereas population growth rates of more than 2.0% were seen in 33 of 46 countries in sub-Saharan Africa. In 2017, less than 65% of the national population was of working age in 12 of 34 high-income countries, and less than 50% of the national population was of working age in Mali, Chad, and Niger. 

    Interpretation Population trends create demographic dividends and headwinds (ie, economic benefits and detriments) that affect national economies and determine national planning needs. Although TFRs are decreasing, the global population continues to grow as mortality declines, with diverse patterns at the national level and across age groups. To our knowledge, this is the first study to provide transparent and replicable estimates of population and fertility, which can be used to inform decision making and to monitor progress. 

  • 249. Murray, Christopher J. L
    et al.
    Ortblad, Katrina F
    Guinovart, Catarina
    Lim, Stephen S
    Wolock, Timothy M
    Roberts, D Allen
    Dansereau, Emily A
    Graetz, Nicholas
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Vos, Theo
    Global, regional, and national incidence and mortality for HIV, tuberculosis, and malaria during 1990-2013: a systematic analysis for the Global Burden of Disease Study 20132014Ingår i: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 384, nr 9947, s. 1005-1070Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The Millennium Declaration in 2000 brought special global attention to HIV, tuberculosis, and malaria through the formulation of Millennium Development Goal (MDG) 6. The Global Burden of Disease 2013 study provides a consistent and comprehensive approach to disease estimation for between 1990 and 2013, and an opportunity to assess whether accelerated progress has occured since the Millennium Declaration. 

    Methods: To estimate incidence and mortality for HIV, we used the UNAIDS Spectrum model appropriately modified based on a systematic review of available studies of mortality with and without antiretroviral therapy (ART). For concentrated epidemics, we calibrated Spectrum models to fit vital registration data corrected for misclassification of HIV deaths. In generalised epidemics, we minimised a loss function to select epidemic curves most consistent with prevalence data and demographic data for all-cause mortality. We analysed counterfactual scenarios for HIV to assess years of life saved through prevention of mother-to-child transmission (PMTCT) and ART. For tuberculosis, we analysed vital registration and verbal autopsy data to estimate mortality using cause of death ensemble modelling. We analysed data for corrected case-notifications, expert opinions on the case-detection rate, prevalence surveys, and estimated cause-specific mortality using Bayesian meta-regression to generate consistent trends in all parameters. We analysed malaria mortality and incidence using an updated cause of death database, a systematic analysis of verbal autopsy validation studies for malaria, and recent studies (2010-13) of incidence, drug resistance, and coverage of insecticide-treated bednets. 

    Findings: Globally in 2013, there were 1.8 million new HIV infections (95% uncertainty interval 1.7 million to 2.1 million), 29.2 million prevalent HIV cases (28.1 to 31.7), and 1.3 million HIV deaths (1.3 to 1.5). At the peak of the epidemic in 2005, HIV caused 1.7 million deaths (1.6 million to 1.9 million). Concentrated epidemics in Latin America and eastern Europe are substantially smaller than previously estimated. Through interventions including PMTCT and ART, 19.1 million life-years (16.6 million to 21.5 million) have been saved, 70.3% (65.4 to 76.1) in developing countries. From 2000 to 2011, the ratio of development assistance for health for HIV to years of life saved through intervention was US$4498 in developing countries. Including in HIV-positive individuals, all-form tuberculosis incidence was 7.5 million (7.4 million to 7.7 million), prevalence was 11.9 million (11.6 million to 12.2 million), and number of deaths was 1.4 million (1.3 million to 1.5 million) in 2013. In the same year and in only individuals who were HIV-negative, all-form tuberculosis incidence was 7.1 million (6.9 million to 7.3 million), prevalence was 11.2 million (10.8 million to 11.6 million), and number of deaths was 1.3 million (1.2 million to 1.4 million). Annualised rates of change (ARC) for incidence, prevalence, and death became negative after 2000. Tuberculosis in HIV-negative individuals disproportionately occurs in men and boys (versus women and girls); 64.0% of cases (63.6 to 64.3) and 64.7% of deaths (60.8 to 70.3). Globally, malaria cases and deaths grew rapidly from 1990 reaching a peak of 232 million cases (143 million to 387 million) in 2003 and 1.2 million deaths (1.1 million to 1.4 million) in 2004. Since 2004, child deaths from malaria in sub-Saharan Africa have decreased by 31.5% (15.7 to 44.1). Outside of Africa, malaria mortality has been steadily decreasing since 1990. 

    Interpretation: Our estimates of the number of people living with HIV are 18.7% smaller than UNAIDS's estimates in 2012. The number of people living with malaria is larger than estimated by WHO. The number of people living with HIV, tuberculosis, or malaria have all decreased since 2000. At the global level, upward trends for malaria and HIV deaths have been reversed and declines in tuberculosis deaths have accelerated. 101 countries (74 of which are developing) still have increasing HIV incidence. Substantial progress since the Millennium Declaration is an encouraging sign of the effect of global action.

  • 250. Naghavi, Mohsen
    et al.
    Wang, Haidong
    Lozano, Rafael
    Davis, Adrian
    Liang, Xiaofeng
    Zhou, Maigeng
    Vollset, Stein Emil
    Abbasoglu Ozgoren, Ayse
    Abdalla, Safa
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the Global Burden of Disease Study 20132015Ingår i: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 385, nr 9963, s. 117-171Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background

    Up-to-date evidence on levels and trends for age-sex-specific all-cause and cause-specific mortality is essential for the formation of global, regional, and national health policies. In the Global Burden of Disease Study 2013 (GBD 2013) we estimated yearly deaths for 188 countries between 1990, and 2013. We used the results to assess whether there is epidemiological convergence across countries.

    Methods

    We estimated age-sex-specific all-cause mortality using the GBD 2010 methods with some refinements to improve accuracy applied to an updated database of vital registration, survey, and census data. We generally estimated cause of death as in the GBD 2010. Key improvements included the addition of more recent vital registration data for 72 countries, an updated verbal autopsy literature review, two new and detailed data systems for China, and more detail for Mexico, UK, Turkey, and Russia. We improved statistical models for garbage code redistribution. We used six different modelling strategies across the 240 causes; cause of death ensemble modelling (CODEm) was the dominant strategy for causes with sufficient information. Trends for Alzheimer's disease and other dementias were informed by meta-regression of prevalence studies. For pathogen-specific causes of diarrhoea and lower respiratory infections we used a counterfactual approach. We computed two measures of convergence (inequality) across countries: the average relative difference across all pairs of countries (Gini coefficient) and the average absolute difference across countries. To summarise broad findings, we used multiple decrement life-tables to decompose probabilities of death from birth to exact age 15 years, from exact age 15 years to exact age 50 years, and from exact age 50 years to exact age 75 years, and life expectancy at birth into major causes. For all quantities reported, we computed 95% uncertainty intervals (UIs). We constrained cause-specific fractions within each age-sex-country-year group to sum to all-cause mortality based on draws from the uncertainty distributions.

    Findings

    Global life expectancy for both sexes increased from 65·3 years (UI 65·0–65·6) in 1990, to 71·5 years (UI 71·0–71·9) in 2013, while the number of deaths increased from 47·5 million (UI 46·8–48·2) to 54·9 million (UI 53·6–56·3) over the same interval. Global progress masked variation by age and sex: for children, average absolute differences between countries decreased but relative differences increased. For women aged 25–39 years and older than 75 years and for men aged 20–49 years and 65 years and older, both absolute and relative differences increased. Decomposition of global and regional life expectancy showed the prominent role of reductions in age-standardised death rates for cardiovascular diseases and cancers in high-income regions, and reductions in child deaths from diarrhoea, lower respiratory infections, and neonatal causes in low-income regions. HIV/AIDS reduced life expectancy in southern sub-Saharan Africa. For most communicable causes of death both numbers of deaths and age-standardised death rates fell whereas for most non-communicable causes, demographic shifts have increased numbers of deaths but decreased age-standardised death rates. Global deaths from injury increased by 10·7%, from 4·3 million deaths in 1990 to 4·8 million in 2013; but age-standardised rates declined over the same period by 21%. For some causes of more than 100 000 deaths per year in 2013, age-standardised death rates increased between 1990 and 2013, including HIV/AIDS, pancreatic cancer, atrial fibrillation and flutter, drug use disorders, diabetes, chronic kidney disease, and sickle-cell anaemias. Diarrhoeal diseases, lower respiratory infections, neonatal causes, and malaria are still in the top five causes of death in children younger than 5 years. The most important pathogens are rotavirus for diarrhoea and pneumococcus for lower respiratory infections. Country-specific probabilities of death over three phases of life were substantially varied between and within regions.

    Interpretation

    For most countries, the general pattern of reductions in age-sex specific mortality has been associated with a progressive shift towards a larger share of the remaining deaths caused by non-communicable disease and injuries. Assessing epidemiological convergence across countries depends on whether an absolute or relative measure of inequality is used. Nevertheless, age-standardised death rates for seven substantial causes are increasing, suggesting the potential for reversals in some countries. Important gaps exist in the empirical data for cause of death estimates for some countries; for example, no national data for India are available for the past decade.

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