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  • 51.
    Carlsson, Axel C.
    et al.
    Karolinska Institutet.
    Nordquist, Lina
    Uppsala Universitet.
    Larsson, Tobias E.
    Karolinska Institutet.
    Carrero, Juan-Jesus
    Karolinska Institutet.
    Larsson, Anders
    Uppsala Universitet.
    Lind, Lars
    Uppsala university hospital.
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Uppsala universitet.
    Soluble tumor necrosis factor receptor 1 is associated with glomerular filtration rate progression and incidence of chronic kidney disease in two community-based cohorts of elderly individuals2015Ingår i: CardioRenal Medicine, ISSN 1664-3828, Vol. 5, nr 4, s. 278-288Artikel i tidskrift (Refereegranskat)
    Abstract [en]

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

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

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

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

  • 52. Carlsson, Axel C
    et al.
    Nowak, Christoph
    Lind, Lars
    Östgren, Carl Johan
    Nyström, Fredrik H
    Sundström, Johan
    Carrero, Juan Jesus
    Riserus, Ulf
    Ingelsson, Erik
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Karolinska Institutet.
    Growth differentiation factor 15 (GDF-15) is a potential biomarker of both diabetic kidney disease and future cardiovascular events in cohorts of individuals with type 2 diabetes: a proteomics approach2019Ingår i: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, s. 1-7Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Diabetic kidney disease (DKD) is a leading risk factor for end-stage renal disease and is one of the most important risk factors for cardiovascular disease in patients with diabetes. It is possible that novel markers portraying the pathophysiological underpinning processes may be useful.Aim: To investigate the associations between 80 circulating proteins, measured by a proximity extension assay, and prevalent DKD and major adverse cardiovascular events (MACE) in type 2 diabetes.Methods: We randomly divided individuals with type 2 diabetes from three cohorts into a two-thirds discovery and one-third replication set (total n = 813, of whom 231 had DKD defined by estimated glomerular filtration rate <60 mg/mL/1.73 m2 and/or urinary albumin-creatinine ratio ≥3 g/mol). Proteins associated with DKD were also assessed as predictors for incident major adverse cardiovascular events (MACE) in persons with DKD at baseline.Results: Four proteins were positively associated with DKD in models adjusted for age, sex, cardiovascular risk factors, glucose control, and diabetes medication: kidney injury molecule-1 (KIM-1, odds ratio [OR] per standard deviation increment, 1.65, 95% confidence interval [CI] 1.27-2.14); growth differentiation factor 15 (GDF-15, OR 1.40, 95% CI 1.16-1.69); myoglobin (OR 1.57, 95% CI 1.30-1.91), and matrix metalloproteinase 10 (MMP-10, OR 1.43, 95% CI 1.17-1.74). In patients with DKD, GDF-15 was significantly associated with increased risk of MACE after adjustments for baseline age, sex, microalbuminuria, and kidney function and (59 MACE events during 7 years follow-up, hazard ratio per standard deviation increase 1.43 [95% CI 1.03-1.98]) but not after further adjustments for cardiovascular risk factors.Conclusion: Our proteomics approach confirms and extends previous associations of higher circulating levels of GDF-15 with both micro- and macrovascular disease in patients with type 2 diabetes. Our data encourage additional studies evaluating the clinical utility of our findings.

  • 53. Carlsson, Axel C.
    et al.
    Riserus, Ulf
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Hypertriglyceridemic waist phenotype is associated with decreased insulin sensitivity and incident diabetes in elderly men2014Ingår i: Obesity, ISSN 1930-7381, E-ISSN 1930-739X, Vol. 22, nr 2, s. 526-529Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: To investigate the association between hypertriglyceridemic waist (HTGW) and insulin sensitivity (assessed by euglycemic clamp method), and the development of diabetes in a longitudinal community-based cohort of elderly men without diabetes at baseline.

    Design and Methods: The present cross-sectional study comprised 1,026, 70-year-old men without diabetes. The gold standard euglycaemic-hyperinsulinaemic clamp technique was used. Six-year follow-up on diabetes status were available in n = 667. The HTGW phenotype was defined as having waist circumference >= 90 cm, and triglycerides >= 2 mmol L-1. The men were stratified into those having normal WC and TG (n = 299), one HTGW component (n = 606), and HTGW (n = 121).

    Results: The association between insulin sensitivity and one HTGW component as well as HTGW was highly significant (P < 0.001) in the whole sample, as well as in individuals with high/low BMI (stratified at >= 25). In longitudinal analyses, participants with HTGW was associated with a more than fourfold increased risk for diabetes (Odds ratio 4.64, 95% CI 1.61-13.4, P = 0.004) compared to those with normal WC and TG.

    Conclusion: The present study both confirm and extend previous research suggesting that the HTGW-phenotype portrays an increased glucometabolic risk, also in lean individuals.

  • 54. Carlsson, Axel C
    et al.
    Ruge, Toralph
    Kjøller, Erik
    Hilden, Jørgen
    Kolmos, Hans Jørn
    Sajadieh, Ahmad
    Kastrup, Jens
    Jensen, Gorm Boje
    Larsson, Anders
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Karolinska institutet.
    10-year associations between tumor necrosis factor receptors 1 and 2 and cardiovascular events in patients with stable coronary heart disease: a CLARICOR (effect of clarithromycin on mortality and morbidity in patients with ischemic heart disease) trial substudy2018Ingår i: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 7, nr 9, artikel-id e008299Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: We aimed to assess the associations and predictive powers between the soluble receptors for tumor necrosis factor (TNF)-α (TNFR1 and TNFR2) and cardiovascular outcomes in patients with stable coronary heart disease.

    METHODS AND RESULTS: <0.001 for TNFR2). The associations were similar in the replication sample. The associations with the composite outcome were mainly driven by acute myocardial infarction, cardiovascular mortality, and noncardiovascular mortality. The addition of TNFR1 and TNFR2 to established cardiovascular risk factors improved prediction only modestly (<1%).

    CONCLUSIONS: Increased concentrations of circulating TNFR1 and TNFR2 were associated with increased risks of cardiovascular events and mortality in patients with stable coronary heart disease. Yet, the utility of measuring TNFR1 and TNFR2 to improve risk prediction in these patients appears limited.

    CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00121550.

  • 55. Carlsson, Axel C
    et al.
    Ruge, Toralph
    Sundström, Johan
    Ingelsson, Erik
    Larsson, Anders
    Lind, Lars
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Association between circulating endostatin, hypertension duration, and hypertensive target-organ damage2013Ingår i: Hypertension, ISSN 0194-911X, E-ISSN 1524-4563, Vol. 62, nr 6, s. 1146-1151Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Our aim is to study associations between circulating endostatin, hypertension duration, and hypertensive target-organ damage. Long-term hypertension induces cardiovascular and renal remodeling. Circulating endostatin, a biologically active derivate of collagen XVIII, has been suggested to be a relevant marker for extracellular matrix turnover and remodeling in various diseases. However, the role of endostatin in hypertension and hypertensive target-organ damage is unclear. Serum endostatin was measured in 2 independent community-based cohorts: the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS; women 51%; n=812; mean age, 75 years) and the Uppsala Longitudinal Study of Adult Men (ULSAM; n=785; mean age, 77.6 years). Retrospective data on blood pressure measurements and antihypertensive medication (PIVUS >5 years, ULSAM >27 years), and cross-sectional data on echocardiographic left ventricular mass, endothelial function (endothelium-dependent vasodilation assessed by the invasive forearm model), and urinary albumin/creatinine ratio were available. In PIVUS, participants with ≥5 years of history of hypertension portrayed 0.42 SD (95% confidence interval, 0.23-0.61; P<0.001) higher serum endostatin, compared with that of normotensives. This association was replicated in ULSAM, in which participants with 27 years hypertension duration had the highest endostatin (0.57 SD higher; 95% confidence interval, 0.35-0.80; P<0.001). In addition, higher endostatin was associated with higher left ventricular mass, worsened endothelial function, and higher urinary albumin/creatinine ratio (P<0.03 for all) in participants with prevalent hypertension. Circulating endostatin is associated with the duration of hypertension, and vascular, myocardial, and renal indices of hypertensive target-organ damage. Further studies are warranted to assess the prognostic role of endostatin in individuals with hypertension.

  • 56. Carlsson, Axel C
    et al.
    Sundström, Johan
    Carrero, Juan Jesus
    Gustafsson, Stefan
    Stenemo, Markus
    Larsson, Anders
    Lind, Lars
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Uppsala University.
    Use of a proximity extension assay proteomics chip to discover new biomarkers associated with albuminuria.2017Ingår i: European Journal of Preventive Cardiology, ISSN 2047-4873, E-ISSN 2047-4881, Vol. 24, nr 4, s. 340-348Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: The underlying mechanisms for the development of albuminuria and the increased cardiovascular risk in patients with elevated albuminuria levels are incompletely understood. We therefore investigated the associations between 80 cardiovascular proteins and the urinary albumin to creatinine ratio (ACR).

    METHODS: We used a discovery/replication approach in two independent community-based cohorts of elderly patients: the Uppsala Longitudinal Study of Adult Men (n = 662; mean age 78 years) and the Prospective Investigation of the Vasculature in Uppsala Seniors (n = 757; mean age 75 years; 51% women). A proteomic chip with a panel of 80 plasma proteins associated with different aspects of cardiovascular disease was analysed. In the discovery cohort, we used a false discovery rate of 5% to take into account the multiple statistical testing. Nominal p values were used in the replication.

    RESULTS: Higher levels of T-cell immunoglobulin mucin-1, placenta growth factor, growth/differentiation factor-15, urokinase plasminogen activator surface receptor and kallikrein-11 were robustly associated with a higher ACR in both cohorts in multivariable linear regression models adjusted for sex, established cardiovascular risk factors, antihypertensive treatment, prevalent cardiovascular disease and glomerular filtration rate (p < 0.02 for all). All associations were also significant in separate analyses of patients without diabetes.

    CONCLUSIONS: We discovered and replicated associations between ACR and five cardiovascular proteins involved in tubular injury, atherosclerosis, endothelial function, heart failure, inflammation, glomerulosclerosis and podocyte injury. Our findings put forward multiplex proteomics as a promising approach to explore novel aspects of the complex detrimental interplay between kidney function and the cardiovascular system.

  • 57. Carlsson, Axel C
    et al.
    Wessman, T
    Larsson, A
    Leijonberg, G
    Tofik, R
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Karolinska Institutet.
    Melander, O
    Ruge, T
    Endostatin predicts mortality in patients with acute dyspnea - a cohort study of patients seeking care in emergency departments.2019Ingår i: Clinical Biochemistry, ISSN 0009-9120, E-ISSN 1873-2933, artikel-id S0009-9120(19)30514-4Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Increased levels of circulating endostatin predicts cardiovascular morbidity and impaired kidney function in the general population. The utility of endostatin as a risk marker for mortality in the emergency department (ED) has not been reported.

    AIM: Our main aim was to study the association between plasma endostatin and 90-day mortality in an unselected cohort of patients admitted to the ED for acute dyspnea. Design Circulating endostatin was analyzed in plasma from 1710 adults and related to 90-day mortality in Cox proportional hazard models adjusted for age, sex, body mass index, oxygen saturation, respiratory rate, body temperature, C-reactive protein, lactate, creatinine and medical priority according to the Medical Emergency Triage and Treatment System-Adult score (METTS-A). The predictive value of endostatin for mortality was evaluated with receiver operating characteristic (ROC) analysis and compared with the clinical triage scoring system and age.

    RESULTS: Each one standard deviation increment of endostatin was associated with a HR of 2.12 (95 % CI 1.31-3.44 p< 0.01) for 90-day mortality after full adjustment. Levels of endostatin were significantly increased in the group of patients with highest METTS-A (p<0.001). When tested for the outcome 90-day mortality, the area under the ROC curve (AUC) was 0.616 for METTS-A, 0.701 for endostatin, 0.708 for METTS -A and age and 0.738 for METTS-A, age and levels of endostatin.

    CONCLUSIONS: In an unselected cohort of patients admitted to the ED with acute dyspnea, endostatin had a string association to 90-day mortality and improved prediction of 90-day mortality in the ED beyond the clinical triage scoring system and age with 3 %.

  • 58. Carlsson, Axel C
    et al.
    Wändell, Per
    Riserus, Ulf
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Uppsala universitet.
    Borné, Yan
    Engström, Gunnar
    Leander, Karin
    Gigante, Bruna
    Hellénius, Mai-Lis
    de Faire, Ulf
    Differences in anthropometric measures in immigrants and Swedish-born individuals: results from two community-based cohort studies2014Ingår i: Preventive Medicine, ISSN 0091-7435, E-ISSN 1096-0260, Vol. 69, s. 151-156Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    AIM: To study differences in body mass index (BMI), waist-hip ratio (WHR), waist circumference (WC), sagittal abdominal diameter (SAD), waist-hip-height ratio (WHHR) and percent body fat in immigrants and Swedish-born men and women in two large population-based samples.

    METHODS: A cross-sectional analysis of 60-year-old individuals, n=4 232. To replicate the results, we also assessed another large independent cohort cross-sectionally, the Malmö Diet and Cancer Study (MDC, n=26 777). The data from both cohorts were collected in the 1990s in Sweden.

    RESULTS: Significant differences between Finnish-born, Middle Eastern and women from the rest of the world were seen for all anthropometric measures, using Swedish-born women as referent. However, WHHR was the only anthropometric measure that identified all these three groups of immigrant women as different from Swedish-born women with high statistical certainty (p<0.001). Apart from WHHR that identified differences in anthropometry in all immigrant groups of men using Swedish-born men as referent, few significant differences were seen in anthropometry among groups of immigrant men. These finding were observed in both cohorts, and remained after adjustments for smoking, physical activity and educational level.

    CONCLUSION: The present study confirms previous findings of more obesity among immigrants and is the first to report that WHHR measurements may detect anthropometric differences between different ethnic groups better than other anthropometrical measures.

  • 59. Carlsson, Axel C
    et al.
    Östgren, Carl Johan
    Nystrom, Fredrik H
    Länne, Toste
    Jennersjö, Pär
    Larsson, Anders
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Uppsala universitet.
    Association of soluble tumor necrosis factor receptors 1 and 2 with nephropathy, cardiovascular events, and total mortality in type 2 diabetes2016Ingår i: Cardiovascular Diabetology, ISSN 1475-2840, E-ISSN 1475-2840, Vol. 15, artikel-id 40Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    AIMS/HYPOTHESIS: Soluble tumor necrosis factor receptors 1 and 2 (sTNFR1 and sTNFR2) contribute to experimental diabetic kidney disease, a condition with substantially increased cardiovascular risk when present in patients. Therefore, we aimed to explore the levels of sTNFRs, and their association with prevalent kidney disease, incident cardiovascular disease, and risk of mortality independently of baseline kidney function and microalbuminuria in a cohort of patients with type 2 diabetes. In pre-defined secondary analyses we also investigated whether the sTNFRs predict adverse outcome in the absence of diabetic kidney disease.

    METHODS: The CARDIPP study, a cohort study of 607 diabetes patients [mean age 61 years, 44 % women, 45 cardiovascular events (fatal/non-fatal myocardial infarction or stroke) and 44 deaths during follow-up (mean 7.6 years)] was used.

    RESULTS: Higher sTNFR1 and sTNFR2 were associated with higher odds of prevalent kidney disease [odd ratio (OR) per standard deviation (SD) increase 1.60, 95 % confidence interval (CI) 1.32-1.93, p < 0.001 and OR 1.54, 95 % CI 1.21-1.97, p = 0.001, respectively]. In Cox regression models adjusting for age, sex, glomerular filtration rate and urinary albumin/creatinine ratio, higher sTNFR1 and sTNFR2 predicted incident cardiovascular events [hazard ratio (HR) per SD increase, 1.66, 95 % CI 1.29-2.174, p < 0.001 and HR 1.47, 95 % CI 1.13-1.91, p = 0.004, respectively]. Results were similar in separate models with adjustments for inflammatory markers, HbA1c, or established cardiovascular risk factors, or when participants with diabetic kidney disease at baseline were excluded (p < 0.01 for all). Both sTNFRs were associated with mortality.

    CONCLUSIONS/INTERPRETATIONS: Higher circulating sTNFR1 and sTNFR2 are associated with diabetic kidney disease, and predicts incident cardiovascular disease and mortality independently of microalbuminuria and kidney function, even in those without kidney disease. Our findings support the clinical utility of sTNFRs as prognostic markers in type 2 diabetes.

  • 60.
    Carlsson, Magnus
    et al.
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Carlsson, Tomas
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Hammarström, Daniel
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Idrotts- och hälsovetenskap.
    Granath, Johan
    Westergren, Jens
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Idrotts- och hälsovetenskap.
    Malm, Christer
    Tonkonogi, Michail
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Idrotts- och hälsovetenskap.
    Validation of off-season physiological tests with ski ranking in elite male junior cross-country skiing2012Ingår i: Medicine & Science in Sports & Exercise, ISSN 0195-9131, E-ISSN 1530-0315, Vol. 44, nr s2, s. 516-516Artikel i tidskrift (Övrigt vetenskapligt)
  • 61.
    Carlsson, Magnus
    et al.
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Carlsson, Tomas
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Hammarström, Daniel
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Idrotts- och hälsovetenskap.
    Malm, Christer
    Tonkonogi, Michail
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Idrotts- och hälsovetenskap.
    Time trials predict the competitive performance capacity of junior cross-country skiers2014Ingår i: International Journal of Sports Physiology and Performance, ISSN 1555-0265, E-ISSN 1555-0273, Vol. 9, nr 1, s. 12-18Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose: This study investigated whether there is a correlation between time-trial performance and competitive performance capacity of male and female junior cross-country skiers and sought to explain sex-specific competitive performance capacity through multiple-regression modeling.

    Methods: The International Ski Federation's (FIS) junior ranking points for distance (FISdist) and sprint (FISsprint) competitions were used as performance parameters. A total of 38 elite junior (age 18.5 +/- 1.0 y) cross-country skiers (24 men and 14 women) completed 3 time-trial tests: a 3-km level-running time trial (TTRun), a 2-km moderate uphill (1.2 slope) roller-skiing time trial using the double-poling technique (TTDP), and a 2-km uphill (2.8 slope) roller-skiing time trial using the diagonal-stride technique (TTDiag). The correlations were investigated using Pearson correlation analysis, and regression models were created using multiple-linear-regression analysis. Results: For men, FISsprint and FISdist were correlated with the times for TTRun, TTDP, and TTDiag (all P < .001). For women, FISsprint was correlated with the times for TTRun (P < .05), TTDP (P < .01), and TTDiag (P < .01), whereas FISdist was correlated only with the times for TTDP (P < .01) and TTDiag (P < .05). The models developed for FISdist and FISsprint explained 73.9-82.3% of the variance in the performance capacity of male junior cross-country skiers. No statistically valid regression model was found for the women.

    Conclusions: Running and roller-skiing time trials are useful tests for accurately predicting the performance capacity of junior cross-country skiers.

  • 62.
    Carlsson, Magnus
    et al.
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Idrotts- och hälsovetenskap. Umeå universitet; Dala Sports Academy.
    Carlsson, Tomas
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Idrotts- och hälsovetenskap. Umeå universitet; Dala Sports Academy.
    Wedholm, Lars
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Idrotts- och hälsovetenskap. Dala Sports Academy.
    Nilsson, Mattias
    Regional Sports Federation of Dalarna.
    Malm, Christer
    Idrottsmedicin, Umeå Universitet.
    Tonkonogi, Michail
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Physiological demands of competitive sprint and distance performance in elite female cross-country skiing2016Ingår i: Journal of Strength and Conditioning Research, ISSN 1064-8011, E-ISSN 1533-4287, Vol. 30, nr 8, s. 2138-2144Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The purpose was to investigate the relationship between elite females' competitive performance capability in sprint and distance cross-country skiing and the variables of gross efficiency (GE), work rate at the onset of blood-lactate accumulation (OBLA4mmol), maximal oxygen uptake (VO2max), maximal speed (Vmax), and peak upper-body oxygen uptake (VO2peak). Ten elite female cross-country skiers (age 24.5 ± 2.8 years) completed treadmill roller-skiing tests to determine GE, OBLA4mmol, and VO2max using the diagonal-stride technique as well as Vmax and VO2peak using the double-poling technique. International Ski Federations ranking points for sprint (FISsprint) and distance (FISdist) races were used as competitive performance data. There were correlations between the FISsprint and the VO2max expressed absolutely (P = 0.0040), Vmax (P = 0.012), and VO2peak expressed absolutely (P < 0.001) and as a simple ratio-standard (P = 0.049). The FISdist were correlated with OBLA4mmol (P = 0.048), VO2max expressed absolutely (L·min) (P = 0.015) and as a simple ratio-standard (P = 0.046), and VO2peak expressed absolutely (P = 0.036) and as a simple ratio-standard (mL·min·kg) (P = 0.040). The results demonstrate that the physiological abilities reflected by VO2max and VO2peak are indicators of competitive sprint and distance performance in elite female cross-country skiing. In addition, the ability to generate a high Vmax indicates the performance in sprint races whereas the skier's OBLA4mmol reflects the performance capability in distance races. Based on the results, when evaluating the performance capacity of elite female cross-country skiers, it is recommended to use physiological variables that reflect competitive performance.

  • 63.
    Carlsson, Tomas
    et al.
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Idrotts- och hälsovetenskap.
    Tonkonogi, Michail
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Carlsson, Magnus
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Idrotts- och hälsovetenskap.
    Aerobic power and lean mass are indicators of competitive sprint performance among elite female cross-country skiers2016Ingår i: Open Access Journal of Sports Medicine, ISSN 1179-1543, E-ISSN 1179-1543, Vol. 7, s. 153-160Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The purpose of this study was to establish the optimal allometric models to predict International Ski Federation’s ski-ranking points for sprint competitions (FISsprint) among elite female cross-country skiers based on maximal oxygen uptake (V̇O2max) and lean mass (LM). Ten elite female cross-country skiers (age: 24.5±2.8 years [mean ± SD]) completed a treadmill roller-skiing test to determine V̇O2max (ie, aerobic power) using the diagonal stride technique, whereas LM (ie, a surrogate indicator of anaerobic capacity) was determined by dual-emission X-ray anthropometry. The subjects’ FISsprint were used as competitive performance measures. Power function modeling was used to predict the skiers’ FISsprint based on V̇O2max, LM, and body mass. The subjects’ test and performance data were as follows: V̇O2max, 4.0±0.3 L min-1; LM, 48.9±4.4 kg; body mass, 64.0±5.2 kg; and FISsprint, 116.4±59.6 points. The following power function models were established for the prediction of FISsprint: 3.91×105 ∙ VO -6.002maxand 6.95×1010 ∙ LM-5.25; these models explained 66% (P=0.0043) and 52% (P=0.019), respectively, of the variance in the FISsprint. Body mass failed to contribute to both models; hence, the models are based on V̇O2max and LM expressed absolutely. The results demonstrate that the physiological variables that reflect aerobic power and anaerobic capacity are important indicators of competitive sprint performance among elite female skiers. To accurately indicate performance capability among elite female skiers, the presented power function models should be used. Skiers whose V̇O2max differs by 1% will differ in their FISsprint by 5.8%, whereas the corresponding 1% difference in LM is related to an FISsprint difference of 5.1%, where both differences are in favor of the skier with higher V̇O2max or LM. It is recommended that coaches use the absolute expression of these variables to monitor skiers’ performance-related training adaptations linked to changes in aerobic power and anaerobic capacity.

  • 64. Carrero, Juan Jesús
    et al.
    Grams, Morgan E
    Sang, Yingying
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Uppsala universitet.
    Gasparini, Alessandro
    Matsushita, Kunihiro
    Qureshi, Abdul R
    Evans, Marie
    Barany, Peter
    Coresh, Josef
    Albuminuria changes are associated with subsequent risk of end-stage renal disease and mortality2017Ingår i: Kidney International, ISSN 0085-2538, E-ISSN 1523-1755, Vol. 91, nr 1, s. 244-251Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Current guidelines for chronic kidney disease (CKD) recommend using albuminuria as well as estimated glomerular filtration rate (eGFR) to stage CKD. However, CKD progression is solely defined by change in eGFR with little regard to the risk implications of change in albuminuria. This is an observational study from the Stockholm CREAtinine Measurements (SCREAM) project, a health care utilization cohort from Stockholm, Sweden, with laboratory measures from 2006-2011 and follow-up through December 2012. Included were 31,732 individuals with two or more ambulatory urine albumin to creatinine ratio (ACR) tests. We assessed the association between change in ACR during a baseline period of 1, 2, or 3 years and end-stage renal disease (ESRD) or death. Using a 2-year baseline period, there were 378 ESRD events and 1712 deaths during a median of 3 years of follow-up. Compared to stable ACR, a 4-fold increase in ACR was associated with a 3.08-times (95% confidence interval 2.59 to 3.67) higher risk of ESRD while a 4-fold decrease in ACR was associated with a 0.34-times (0.26 to 0.45) lower risk of ESRD. Similar associations were found in people with and without diabetes mellitus, with and without hypertension, and also when adjusted for the change in eGFR during the same period. The association between change in ACR and mortality was weaker: ACR increase was associated with mortality, but the relationship was largely flat for ACR decline. Results were consistent for 1-, 2-, and 3-year ACR changes. Thus, changes in albuminuria are strongly and consistently associated with the risk of ESRD and death.

  • 65.
    Carstensen, Gunilla
    et al.
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Sociologi.
    Rosberg, Birgitta
    Uppsala University Hospital.
    McKee, Kevin
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Socialt arbete.
    Åberg, Anna Cristina
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Uppsala University.
    Before evening falls: Perspectives of a good old age and healthy ageing among oldest-old Swedish men2019Ingår i: Archives of gerontology and geriatrics (Print), ISSN 0167-4943, E-ISSN 1872-6976, Vol. 82, s. 35-44Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The late life experiences of men in the oldest-old age group have been under-researched, and their perspectives on ageing successfully neglected. This study explored the perspectives of oldest-old Swedish men on what a ‘good old age’ and ageing successfully meant to them. A purposive sample of 17 men, aged 85-90 years, was drawn from the Uppsala Longitudinal Study of Adult Men. An interview guide explored participants’ perspectives on their ageing experiences and how they viewed ageing successfully. Participants were interviewed twice, with 1–2 weeks between interviews, and both interviews were recorded and transcribed. Content analysis identified four themes: i) Adaptation, concerning the ability to adapt to growing old with increasing limitations; ii) Sustaining Independence, related to financial resources and good health as the foundation for independence; iii) Belongingness, representing close relationships, established friendships, and the significance of the spouse; and iv) Perspectives of Time, also a common thread in all themes, in which past life experiences create an existential link between the past, the present and the future, establishing continuity of the self and enhancing life satisfaction. The participants presented themselves as active agents involved in maintaining meaning and achieving life satisfaction; a process related to the ability to manage changes in life. Our findings have resonance with models of healthy or successful ageing, but also diverge in important ways, since such models do not consider the significance of an individual’s life history for their present well-being, and primarily conceptualise health as an outcome, rather than as a resource.

  • 66. Cederholm, Tommy
    et al.
    Kirn, Dylan R.
    Koochek, Afsaneh
    Reid, Kieran F.
    von Berens, Åsa
    Travison, Thomas G.
    Folta, Sara
    Sacheck, Jennifer
    Åberg, Anna Cristina
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Uppsala University.
    Fielding, Roger A.
    Effect of nutritional supplementation and structured physical activity on physical function in mobility-limited older adults: results from the VIVE2 study2015Konferensbidrag (Refereegranskat)
  • 67.
    Cedervall, Jessica
    et al.
    Uppsala Univ, Biomed Ctr, Sci Life Lab, Dept Med Biochem & Microbiol, Box 582, SE-75123 Uppsala, Sweden..
    Dragomir, Anca
    Uppsala Univ, Rudbeck Lab, Dept Immunol Genet & Pathol, Uppsala, Sweden..
    Saupe, Falk
    Uppsala Univ, Biomed Ctr, Sci Life Lab, Dept Med Biochem & Microbiol, Box 582, SE-75123 Uppsala, Sweden..
    Zhang, Yanyu
    Uppsala Univ, Biomed Ctr, Sci Life Lab, Dept Med Biochem & Microbiol, Box 582, SE-75123 Uppsala, Sweden..
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Karolinska institutet.
    Larsson, Erik
    Uppsala Univ, Rudbeck Lab, Dept Immunol Genet & Pathol, Uppsala, Sweden..
    Dimberg, Anna
    Uppsala Univ, Rudbeck Lab, Dept Immunol Genet & Pathol, Uppsala, Sweden..
    Larsson, Anders
    Uppsala Univ, Dept Med Sci, Uppsala, Sweden..
    Olsson, Anna-Karin
    Uppsala Univ, Biomed Ctr, Sci Life Lab, Dept Med Biochem & Microbiol, Box 582, SE-75123 Uppsala, Sweden..
    Pharmacological targeting of peptidylarginine deiminase 4 prevents cancer-associated kidney injury in mice2017Ingår i: Oncoimmunology, ISSN 2162-4011, E-ISSN 2162-402X, Vol. 6, nr 8, artikel-id e1320009Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Renal insufficiency is a frequent cancer-associated problem affecting more than half of all cancer patients at the time of diagnosis. To minimize nephrotoxic effects the dosage of anticancer drugs are reduced in these patients, leading to sub-optimal treatment efficacy. Despite the severity of this cancer-associated pathology, the molecular mechanisms, as well as therapeutic options, are still largely lacking. We here show that formation of intravascular tumor-induced neutrophil extracellular traps (NETs) is a cause of kidney injury in tumor-bearing mice. Analysis of clinical biomarkers for kidney function revealed impaired creatinine clearance and elevated total protein levels in urine from tumor-bearing mice. Electron microscopy analysis of the kidneys from mice with cancer showed reversible pathological signs such as mesangial hypercellularity, while permanent damage such as fibrosis or necrosis was not observed. Removal of NETs by treatment with DNase I, or pharmacological inhibition of the enzyme peptidylarginine deiminase 4 (PAD4), was sufficient to restore renal function in mice with cancer. Tumor-induced systemic inflammation and impaired perfusion of peripheral vessels could be reverted by the PAD4 inhibitor. In conclusion, the current study identifies NETosis as a previously unknown cause of cancer-associated renal dysfunction and describes a novel promising approach to prevent renal failure in individuals with cancer.

  • 68. Cedervall, Y
    et al.
    Giedraitis, V
    Berglund, L
    McKee, Kevin
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Socialt arbete.
    Kilander, L
    Rosendahl, E
    Ingelsson, M
    Åberg, Anna Cristina
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Timed Up-and-Go dual-task performance – a marker for dementia?2018Konferensbidrag (Refereegranskat)
  • 69. Cedervall, Y
    et al.
    Giedraitis, V
    Berglund, L
    McKee, Kevin
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Socialt arbete.
    Kilander, L
    Rosendahl, E
    Ingelsson, M
    Åberg, Anna Cristina
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Timed Up-and-Go dual-task performance – a marker for dementia?2019Konferensbidrag (Refereegranskat)
  • 70.
    Cedervall, Ylva
    et al.
    Uppsala universitet, Geriatrik.
    Torres, Sandra
    Uppsala universitet.
    Åberg, Anna Cristina
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Uppsala universitet.
    Maintaining well-being and selfhood through physical activity: experiences of people with mild Alzheimer's disease2015Ingår i: Aging & Mental Health, ISSN 1360-7863, E-ISSN 1364-6915, Vol. 19, nr 8, s. 679-688Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives: To contribute to furthering the understanding of how people with mild Alzheimer's disease (AD) reason about physical activity as part of everyday life, with a specific focus on the meanings attached to such activity. 

    Method: In-depth interviews were conducted with 14 individuals with mild AD. Qualitative content analysis was used to interpret the data. 

    Results: The analysis revealed three sub-themes reflecting interrelated perspectives on how people with mild AD reason about physical activity: (1) striving to be physically active, mirrors the concrete approaches used for handling the consequences of having AD in relation to being active; (2) perceptions of physical activity, reflect how their thoughts and beliefs regarding written and tacit norms encouraged them to remain physically active, and (3) physical activity as a means to well-being, alludes to feelings and emotions related to the performance of physical activity. Interpretation of the underlying patterns in these sub-themes revealed one overarching theme: Physical activity as a means to selfhood maintenance, which suggests that physical activity can help to shift the focus from the dementia diagnosis (i.e. ill health) to a more healthy and able self. 

    Conclusion: The findings suggest that physical activity, apart from maintaining body functions, can be a way to sustain well-being and selfhood in mild AD. This aspect of physical activity is important to consider in research, policy and practice when addressing the needs of people with dementia.

  • 71. Coresh, Josef
    et al.
    Heerspink, Hiddo J L
    Sang, Yingying
    Matsushita, Kunihiro
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Karolinska institutet.
    Astor, Brad C
    Black, Corri
    Brunskill, Nigel J
    Carrero, Juan-Jesus
    Gansevoort, Ron T
    Change in albuminuria and subsequent risk of end-stage kidney disease: an individual participant-level consortium meta-analysis of observational studies.2019Ingår i: The Lancet Diabetes and Endocrinology, ISSN 2213-8587, E-ISSN 2213-8595, Vol. 7, nr 2, s. 115-127Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Change in albuminuria as a surrogate endpoint for progression of chronic kidney disease is strongly supported by biological plausibility, but empirical evidence to support its validity in epidemiological studies is lacking. We aimed to assess the consistency of the association between change in albuminuria and risk of end-stage kidney disease in a large individual participant-level meta-analysis of observational studies.

    METHODS: In this meta-analysis, we collected individual-level data from eligible cohorts in the Chronic Kidney Disease Prognosis Consortium (CKD-PC) with data on serum creatinine and change in albuminuria and more than 50 events on outcomes of interest. Cohort data were eligible if participants were aged 18 years or older, they had a repeated measure of albuminuria during an elapsed period of 8 months to 4 years, subsequent end-stage kidney disease or mortality follow-up data, and the cohort was active during this consortium phase. We extracted participant-level data and quantified percentage change in albuminuria, measured as change in urine albumin-to-creatinine ratio (ACR) or urine protein-to-creatinine ratio (PCR), during baseline periods of 1, 2, and 3 years. Our primary outcome of interest was development of end-stage kidney disease after a baseline period of 2 years. We defined an end-stage kidney disease event as initiation of kidney replacement therapy. We quantified associations of percentage change in albuminuria with subsequent end-stage kidney disease using Cox regression in each cohort, followed by random-effects meta-analysis. We further adjusted for regression dilution to account for imprecision in the estimation of albuminuria at the participant level. We did multiple subgroup analyses, and also repeated our analyses using participant-level data from 14 clinical trials, including nine clinical trials not in CKD-PC.

    FINDINGS: Between July, 2015, and June, 2018, we transferred and analysed data from 28 cohorts in the CKD-PC, which included 693 816 individuals (557 583 [80%] with diabetes). Data for 675 904 individuals and 7461 end-stage kidney disease events were available for our primary outcome analysis. Change in ACR was consistently associated with subsequent risk of end-stage kidney disease. The adjusted hazard ratio (HR) for end-stage kidney disease after a 30% decrease in ACR during a baseline period of 2 years was 0·83 (95% CI 0·74-0·94), decreasing to 0·78 (0·66-0·92) after further adjustment for regression dilution. Adjusted HRs were fairly consistent across cohorts and subgroups (ie, estimated glomerular filtration rate, diabetes, and sex), but the association was somewhat stronger among participants with higher baseline ACR than among those with lower baseline ACR (pinteraction<0·0001). In individuals with baseline ACR of 300 mg/g or higher, a 30% decrease in ACR over 2 years was estimated to confer a more than 1% absolute reduction in 10-year risk of end-stage kidney disease, even at early stages of chronic kidney disease. Results were generally similar when we used change in PCR and when study populations from clinical trials were assessed.

    INTERPRETATION: Change in albuminuria was consistently associated with subsequent risk of end-stage kidney disease across a range of cohorts, lending support to the use of change in albuminuria as a surrogate endpoint for end-stage kidney disease in clinical trials of progression of chronic kidney disease in the setting of increased albuminuria.

    FUNDING: US National Kidney Foundation and US National Institute of Diabetes and Digestive and Kidney Diseases.

  • 72. Cornelis, Marilyn C
    et al.
    Gustafsson, Stefan
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Karolinska institutet.
    Elmståhl, Sölve
    Söderberg, Stefan
    Sundström, Johan
    Michaëlsson, Karl
    Lind, Lars
    Ingelsson, Erik
    Targeted proteomic analysis of habitual coffee consumption2018Ingår i: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 283, nr 2, s. 200-211Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Coffee drinking has been implicated in mortality and a variety of diseases but potential mechanisms underlying these associations are unclear. Large-scale systems epidemiological approaches may offer novel insights to mechanisms underlying associations of coffee with health.

    OBJECTIVE: We performed an analysis of known and novel protein markers linked to cardiovascular disease and their association with habitual coffee intake in the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS, n=816) and followed-up top proteins in the Uppsala Longitudinal Study of Adult Men (ULSAM, n=635) and EpiHealth (n=2418).

    METHODS: In PIVUS and ULSAM, coffee intake was measured by 7-day dietary records while a computer-based food frequency questionnaire was used in EpiHealth. Levels of up to 80 proteins were assessed in plasma by a proximity extension assay.

    RESULTS: Four protein-coffee associations adjusted for age, sex, smoking and BMI, met statistical significance in PIVUS (FDR<5%, P<2.31×10(-3) ): leptin (LEP), chitinase-3-like protein 1 (CHI3L), Tumor necrosis factor (TNF) receptor 6 and TNF-related apoptosis-inducing ligand. The inverse association between coffee intake and LEP replicated in ULSAM (β, -0.042 SD per cup of coffee, P=0.028) and EpiHealth (β, -0.025 SD per time of coffee, P=0.004). The negative coffee-CHI3L association replicated in EpiHealth (β, -0.07, P=1.15×10(-7) ), but not in ULSAM (β, -0.034, P=0.16).

    CONCLUSIONS: The current study supports an inverse association between coffee intake and plasma LEP and CHI3L1 levels. The coffee-CHI3L1 association is novel and warrants further investigation given links between CHI3L1 and health conditions that are also potentially influenced by coffee. 

  • 73. Corsonello, Andrea
    et al.
    Roller-Wirnsberger, Regina
    Di Rosa, Mirko
    Fabbietti, Paolo
    Wirnsberger, Gerhard
    Kostka, Tomasz
    Guligowska, Agnieszka
    Tap, Lisanne
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Uppsala University; Karolinska Institutet.
    Lattanzio, Fabrizia
    Estimated glomerular filtration rate and functional status among older people: A systematic review2018Ingår i: European journal of internal medicine, ISSN 0953-6205, E-ISSN 1879-0828, Vol. 56, nr SI, s. 39-48Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: The association between chronic kidney disease (CKD) and functional status may change as a function of the equation used to estimate glomerular filtration rate (eGFR). We reviewed the predictive value of different eGFR equations in regard to frailty and disability outcomes.

    METHODS: We searched Pubmed from inception to March 2018 for studies investigating the association between eGFR and self-reported and/or objective measures of frailty or disability. Cross-sectional and longitudinal studies were separately analysed.

    RESULTS: We included 16 studies, one of which reporting both cross-sectional and longitudinal data. Three out of 7 cross-sectional studies compared different eGFR equations in regard to their association with functional status: two studies showed that cystatin C-based, but not creatinine-based eGFR may be associated with hand-grip strength or frailty; another study showed that two different creatinine-based eGFR equations may be similarly associated with disability. Four out of 10 longitudinal studies provided comparative data: two studies reported similar association with disability for different creatinine-based eGFR equations; one study showed that creatinine-based eGFR was not associated with frailty, but a not significant trend for association was observed with cystatin C-based eGFR; one study showed that cystatin C-based but not creatinine-based eGFR may predict incident mobility disability, while both methods may predict gait speed decline. High heterogeneity was observed in regard to confounders included in reviewed studies. None of them included the most recently published equations.

    CONCLUSION: Available data do not support the superiority of one of the eGFR equations in terms of measuring or predicting functional decline.

  • 74. Corsonello, Andrea
    et al.
    Roller-Wirnsberger, Regina
    Wirnsberger, Gerhard
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Uppsala University / Karolinska Institutet.
    Carlsson, Axel C
    Tap, Lisanne
    Mattace-Raso, Francesco
    Formiga, Francesc
    Moreno-Gonzalez, Rafael
    Lattanzio, Fabrizia
    Clinical Implications of Estimating Glomerular Filtration Rate with Three Different Equations Among Older People. Preliminary Results of the Project "Screening for Chronic Kidney Disease among Older People across Europe (SCOPE)".2020Ingår i: Journal of clinical medicine, ISSN 2077-0383, Vol. 9, nr 2, artikel-id E294Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We aimed at investigating to what extent CKD may be staged interchangeably by three different eGFR equations in older people, and evaluating the source of discrepancies among equations in a population of 2257 patients older than 75 years enrolled in a multicenter observational study. eGFR was calculated by CKD-EPI, BIS and FAS equations. Statistical analysis was carried out by Bland-Altman analysis. κ statistic was used to quantify the agreement between equations in classifying CKD stages. The impact of selected variables on the difference among equations was graphically explored. The average difference between BIS and FAS was -0.24 (95% limits of agreement (95%LA = -4.64-4.14) mL/min/1.73 m2. The difference between CKD-EPI and BIS and between CKD-EPI and FAS was 8.97 (95%LA = -2.90-20.84) and 8.72 (95%LA = -2.11-19.56) mL/min/1.73 m2, respectively. As regards CKD stage classification, κ value was 0.47 for both CKD-EPI vs. FAS and CKD-EPI vs. BIS, while BIS and FAS had similar classificatory properties (κ = 0.90). Muscle mass was found related to the difference between CKD-EPI and BIS (R2 = 0.11) or FAS (R2 = 0.14), but not to the difference between BIS and FAS. In conclusion, CKD-EPI and BIS/FAS equations are not interchangeable to assess eGFR among older people. Muscle mass may represent a relevant source of discrepancy among eGFR equations.

  • 75. Corsonello, Andrea
    et al.
    Tap, Lisanne
    Roller-Wirnsberger, Regina
    Wirnsberger, Gerhard
    Zoccali, Carmine
    Kostka, Tomasz
    Guligowska, Agnieszka
    Fuentes, Lara Guardado
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Uppsala universitet; Karolinska institutet.
    Lattanzio, Fabrizia
    Design and methodology of the screening for CKD among older patients across Europe (SCOPE) study: a multicenter cohort observational study.2018Ingår i: BMC Nephrology, ISSN 1471-2369, E-ISSN 1471-2369, Vol. 19, nr 1, artikel-id 260Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Decline of renal function is common in older persons and the prevalence of chronic kidney disease (CKD) is rising with ageing. CKD affects different outcomes relevant to older persons, additionally to morbidity and mortality which makes CKD a relevant health burden in this population. Still, accurate laboratory measurement of kidney function is under debate, since current creatinine-based equations have a certain degree of inaccuracy when used in the older population. The aims of the study are as follows: to assess kidney function in a cohort of 75+ older persons using existing methodologies for CKD screening; to investigate existing and innovative biomarkers of CKD in this cohort, and to align laboratory and biomarker results with medical and functional data obtained from this cohort. The study was registered at ClinicalTrials.gov, identifier NCT02691546, February 25th 2016.

    METHODS/DESIGN: An observational, multinational, multicenter, prospective cohort study in community dwelling persons aged 75 years and over, visiting the outpatient clinics of participating institutions. The study will enroll 2450 participants and is carried out in Austria, Germany, Israel, Italy, the Netherlands, Poland and Spain. Participants will undergo clinical and laboratory evaluations at baseline and after 12 and 24 months- follow-up. Clinical evaluation also includes a comprehensive geriatric assessment (CGA). Local laboratory will be used for 'basic' parameters (including serum creatinine and albumin-to-creatinine ratio), whereas biomarker assessment will be conducted centrally. An intermediate telephone follow-up will be carried out at 6 and 18 months.

    DISCUSSION: Combining the use of CGA and the investigation of novel and existing independent biomarkers within the SCOPE study will help to provide evidence in the development of European guidelines and recommendations in the screening and management of CKD in older people.

    TRIAL REGISTRATION: This study was registered prospectively on the 25th February 2016 at clinicaltrials.gov ( NCT02691546 ).

  • 76. Cotgreave, Ian
    et al.
    Goldschmidt, Lina
    Tonkonogi, Michail
    Högskolan Dalarna, Akademin Hälsa och samhälle, Medicinsk vetenskap.
    Svensson, Michael
    Differentiation-specific alterations to glutathione synthesis in and hormonally-stimulated release from human skeletal muscle cells.2002Ingår i: The FASEB Journal, ISSN 0892-6638, E-ISSN 1530-6860, Vol. 16, s. 435-437Artikel i tidskrift (Refereegranskat)
  • 77. de Alwis, M.P.
    et al.
    Garme, K:
    Martire, R. Lo
    Kåsin, J.I.
    Äng, Björn
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Centre for Clinical Research Dalarna, Falun, Sweden; Division of Physiotherapy, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden.
    Crew acceleration exposure, health and performance in high-speed operations at sea2017Konferensbidrag (Refereegranskat)
    Abstract [en]

    The presented research program investigates the association between working conditions aboard High-Speed Craft (HSC) and its outcomes in terms of acceleration exposure and crew health and systems performance respectively. The aim is to identify the related risk factors and further, to use them to improve the assessment criteria in a simulation-based-design framework. The investigation initially document a seaborne population by a web-based questionnaire tailored for High-Performance Marine Craft Personnel (HPMCP) and similar populations. Then data is collected during regular service by measuring craft acceleration and through another questionnaire especially resolute on perceived work-exposure, health and performance. Exposure and performance data is collected daily and health data weekly, depending on seaborne frequency. The population repeats the prevalence questionnaire about a year later enabling a longitudinal follow-up for identifying long-term effects of exposure. The paper reports the two questionnaires´ development and pilot test as well as the first application for baseline data collection in the target group. The results indicate health and performance characteristics of the study population and data shows a promising correlation between the self-reported subjective exposure and the measured objective acceleration. Data indicates a comparatively higher prevalence of musculoskeletal pain in the study population than that of the general population.

  • 78. Dicker, Daniel
    et al.
    Nguyen, Grant
    Abate, Degu
    Abate, Lkidan Hassen
    Abay, Solomon
    Abbafati, Cristiana
    Abbasi, Nooshin
    Abbastabar, Hedayat
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Karolinska institutet.
    Murray, Christopher J. L
    Global, regional, and national age-sex-specific mortality and life expectancy, 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. 1684-1735Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background Assessments of age-specific mortality and life expectancy have been done by the UN Population Division, Department of Economics and Social Affairs (UNPOP), the United States Census Bureau, WHO, and as part of previous iterations of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD). Previous iterations of the GBD used population estimates from UNPOP, which were not derived in a way that was internally consistent with the estimates of the numbers of deaths in the GBD. The present iteration of the GBD, GBD 2017, improves on previous assessments and provides timely estimates of the mortality experience of populations globally. 

    Methods The GBD uses all available data to produce estimates of mortality rates between 1950 and 2017 for 23 age groups, both sexes, and 918 locations, including 195 countries and territories and subnational locations for 16 countries. Data used include vital registration systetns, sample registration systetns, household surveys (complete birth histories, summary birth histories, sibling histories), censuses (summary birth histories, household deaths), and Demographic Surveillance Sites. In total, this analysis used 8259 data sources. Estimates of the probability of death between birth and the age of 5 years and between ages 15 and 60 years are generated and then input into a model life table system to produce complete life tables for all locations and years. Fatal discontinuities and mortality due to HIV/AIDS are analysed separately and then incorporated into the estimation. We analyse the relationship between age-specific mortality and development status using the Socio-demographic Index, a composite measure based on fertility under the age of 25 years, education, and income. There are four main methodological improvements in GBD 2017 compared with GBD 2016: 622 additional data sources have been incorporated; new estimates of population, generated by the GBD study, are used; statistical methods used in different components of the analysis have been further standardised and improved; and the analysis has been extended backwards in time by two decades to start in 1950. 

    Findings Globally, 18.7% (95% uncertainty interval 18.4-19.0) of deaths were registered in 1950 and that proportion has been steadily increasing since, with 58.8% (58.2-59.3) of all deaths being registered in 2015. At the global level, between 1950 and 2017, life expectancy increased from 48.1 years (46.5-49.6) to 70.5 years (70.1-70.8) for men and from 52.9 years (51.7-54.0) to 75.6 years (75.3-75.9) for women. Despite this overall progress, there remains substantial variation in life expectancy at birth in 2017, which ranges from 49.1 years (46.5-51.7) for men in the Central African Republic to 87.6 years (86.9-88.1) among women in Singapore. The greatest progress across age groups was for children younger than 5 years; under-5 mortality dropped from 216.0 deaths (196.3-238.1) per 1000 livebirths in 1950 to 38.9 deaths (35.6-42.83) per 1000 livebirths in 2017, with huge reductions across countries. Nevertheless, there were still 5.4 million (5.2-5.6) deaths among children younger than 5 years in the world in 2017. Progress has been less pronounced and more variable for adults, especially for adult tnales, who had stagnant or increasing mortality rates in several countries. The gap between male and female life expectancy between 1950 and 2017, while relatively stable at the global level, shows distinctive patterns across super-regions and has consistently been the largest in central Europe, eastern Europe, and central Asia, and smallest in south Asia. Performance was also variable across countries and time in observed mortality rates compared with those expected on the basis of development. 

    Interpretation This analysis of age-sex-specific mortality shows that there are remarkably complex patterns in population mortality across countries. The findings of this study highlight global successes, such as the large decline in under-5 mortality, which reflects significant local, national, and global commitment and investment over several decades. However, they also bring attention to mortality patterns that are a cause for concern, particularly among adult men and, to a lesser extent, wotnen, whose mortality rates have stagnated in many countries over the time period of this study, and in some cases are increasing.

  • 79. Dunn, Emma
    et al.
    Felthous, Alan R.
    Gagné, Pierre
    Harding, Tim
    Kaliski, Sean
    Kramp, Peter
    Lindqvist, Per
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Karolinska institutet.
    Nedopil, Norbert
    Ogloff, James R. P.
    Skipworth, Jeremy
    Thomson, Lindsay
    Yoshikawa, Kazuo
    Forensic psychiatry and its interfaces outside the UK and Ireland2014Ingår i: Forensic psychiatry: clinical, legal and ethical issues / [ed] Gunn, John C & Taylor, Pamela J, Boca Raton, FL: CRC Press, 2014, 2, s. 112-146Kapitel i bok, del av antologi (Refereegranskat)
  • 80.
    Durbeej, N.
    et al.
    Karolinska institutet.
    Gumpert, C. H.
    Karolinska institutet.
    Alm, C.
    Karolinska institutet.
    Eriksson, Å.
    Karolinska institutet.
    Berman, A. H.
    Karolinska institutet.
    Kristiansson, M.
    Karolinska institutet.
    Lindqvist, Per
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Karolinska institutet.
    Palmstierna, T.
    Karolinska institutet.
    S13-01 - Substance abuse treatment as a predictor of criminal recidivism among psychiatrically examined Swedish offenders2010Ingår i: European psychiatry, ISSN 0924-9338, E-ISSN 1778-3585, Vol. 25, nr Supplement 1, s. 32-32Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Substance abuse is clearly associated with criminal recidivism among offenders with and without mental disorder. Treatment for substance abuse correlates with lower rates of re-offending among participants in outpatient-based as well as institution-based substance abuse treatment programs. However, for offenders with mental disorder, research on the possible preventive effect of substance abuse treatment on criminal recidivism is sparse. This paper reports from on an ongoing naturalistic and prospective interview study on the relationship between post-release outpatient substance abuse treatment and re-offending. Methods: The Stockholm county sample comprises 246 offenders of both genders subjected to a forensic psychiatric assessment, who screened positive for substance abuse problems. Eighty-five percent (n=210) agreed to participate in the study. Baseline data and follow-up interview data, collected immediately on release from incarceration (prison/forensic hospital) and 6 and 12 months later, include self-reported substance abuse, treatment involvement and criminality. By February 2010, data will be available from the first follow-up for 150 participants, from the second follow-up for 80 individuals and from the third follow-up for 10 subjects. Results and conclusions: The focus of the presentation will be recidivism comparisons between substance abuse treatment utilizers and those who decline treatment. Data on ongoing levels of substance abuse, mental health problems and offending will serve as dependent variables. Additional analyses will present perceived benefit from and reasons for accepting or rejecting treatment.

  • 81.
    Durbeej, N.
    et al.
    Karolinska institutet.
    Hellner Gumpert, C.
    Karolinska institutet.
    Alm, C.
    Karolinska institutet.
    Eriksson, Å.
    Karolinska institutet.
    Hephzibah Berman, A.
    Karolinska institutet.
    Kristiansson, M.
    Karolinska institutet.
    Lindqvist, Per
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Karolinska institutet.
    Palmstierna, T.
    Karolinska institutet.
    P02-54 - Is outpatient-based substance abuse treatment a predictor of re-offending and other outcomes among Swedish offenders subjected to psychiatric assessment?2010Ingår i: European psychiatry, ISSN 0924-9338, E-ISSN 1778-3585, Vol. 25, nr Supplement 1, s. 674-674Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction: Substance abuse is associated with criminal recidivism. Substance abuse treatment has been found to correlate negatively with re-offending among treatment utilizers. However, for offenders with mental health problems and substance abuse, research on how substance abuse treatment affects re-offending is sparse. Objectives: The study aimed to examine the relationship between self-reported outpatient-based substance abuse treatment and self-reported a) re-offending, b) substance use and c) psychiatric problems among offenders with mental health and substance use problems. Methods: Data were gathered from a naturalistic follow-up study with 208 participants, subjected to a court-ordered psychiatric assessment. This analysis covers 91 individuals who were followed-up after an average study period of 17 months. Among these, 68% had been sentenced to institutional imprisonment or forensic psychiatric care. Results: Offences, substance use and psychiatric problems declined between baseline and follow-up. However, the reduction was not associated with self-reported treatment utilization. Among participants who were sentenced to non-institutional corrections, more individuals had utilized outpatient-based treatment compared to individuals who were sentenced to imprisonment or forensic psychiatric care. Conclusions: A definitive conclusion about the effect of treatment is difficult to draw. For instance, self-reported data may not reflect actual treatment consumption. However, one interpretation is that participants naturally recovered over time. Institutional correction might also have resulted in positive outcomes equivalent to outpatient-based treatment.

  • 82. Dyson, Kylie
    et al.
    Brown, Siobhan P
    May, Susanne
    Smith, Karen
    Koster, Rudolph W
    Beesems, Stefanie G
    Kuisma, Markku
    Salo, Ari
    Strömsöe, Anneli
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Nichol, Graham
    International variation in survival after out-of-hospital cardiac arrest: a validation study of the Utstein template2019Ingår i: Resuscitation, ISSN 0300-9572, E-ISSN 1873-1570, Vol. 138, s. 168-181Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction: Out-of-hospital cardiac arrest (OHCA) survival varies greatly between communities. The Utstein template was developed and promulgated to improve the comparability of OHCA outcome reports, but it has undergone limited empiric validation. We sought to assess how much of the variation in OHCA survival between emergency medical services (EMS) across the globe is explained by differences in the Utstein factors. We also assessed how accurately the Utstein factors predict OHCA survival.

    Methods: We performed a retrospective analysis of patient-level prospectively collected data from 12 OHCA registries from 12 countries for the period 1 Jan 2006 through 31 Dec 2011. We used generalized linear mixed models to examine the variation in survival between EMS agencies (n = 232).

    Results: Twelve registries contributed 86,759 cases. Patient arrest characteristics, EMS treatment and patient outcomes varied across registries. Overall survival to hospital discharge was 10% (range, 6% to 22%). Overall survival with Cerebral Performance Category of 1 or 2 (available for 8/12 registries) was 8% (range, 2% to 20%). The area-under-the-curve for the Utstein model was 0.85 (Wald CI: 0.85–0.85). The Utstein factors explained 51% of the EMS agency variation in OHCA survival.

    Conclusions: The Utstein factors explained 51% of the variation in survival to hospital discharge among multiple large geographically separate EMS agencies. This suggests that quality improvement and public health efforts should continue to target modifiable Utstein factors to improve OHCA survival. Further study is required to identify the reasons for the variation that is incompletely understood.

  • 83.
    Ekdahl, Victor
    et al.
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Lindblom, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Behandling av iliotibialbandssyndrom hos löpare: En strukturerad litteraturstudie2018Självständigt arbete på avancerad nivå (magisterexamen), 10 poäng / 15 hpStudentuppsats (Examensarbete)
    Abstract [sv]

    Bakgrund: Löpning är en populär motionsform runt om i världen. Iliotibialbandssyndrom (ITBS) är en av de vanligaste överbelastningsskadorna hos löpare. Flera olika konservativa behandlingsmetoder har studerats, men evidensen för dessa är begränsad och otillräcklig för att stödja en specifik behandlingsmetod. Syfte: Att genom en strukturerad litteraturstudie beskriva vilka konservativa behandlingsmetoder som studerats för löpare med ITBS samt vilken effekt dessa behandlingsmetoder rapporterats ha på smärta. Metod: En sökning för att identifiera relevanta artiklar genomfördes i databaserna PubMed, Cinahl, Scoupus och Web of Science. De söktermer som användes var iliotibial band syndrome, iliotibial band friction syndrome och iliotibial band strain. En grovsållning av titlar och abstrakt utfördes. Potentiellt relevanta artiklar hämtades i fulltext, och därefter utfördes en relevansbedömning. Inkluderade artiklars metodologiska kvalité granskades. En etisk granskning utfördes av samtliga inkluderade artiklar. Resultat: Fyra randomiserade kontrollerade studier och två kohortstudier inkluderades. De interventioner som studerades i artiklarna var korrektion av tänkta etiologier till löprelaterade skador, anti-inflammatoriskt / smärtstillande läkemedel, djup tvärfriktionsmassage, höftstärkande rehabiliteringsprogram, kortikosteroid injektion samt stötvågsbehandling jämfört med manuell terapi. Många av interventionerna reducerade smärta, dock i varierande grad. I två av studierna var det ingen signifikant skillnad i reducering av smärta mellan interventions- och kontrollgrupp. Artiklarna hade varierande metodologisk kvalité. Slutsats: Trots att ITBS är vanligt förekommande hos löpare har relativt få studier undersökt dess konservativa behandlingsmetoder. Flera av studierna indikerade positiva resultat i form av smärtreduktion men det föreligger svårigheter i att dra slutsatser om effekt från behandlingsmetoderna på grund av metodologiska svagheter.

  • 84.
    Elf, Marie
    et al.
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Omvårdnad. Karolinska institutet.
    Nordmark, Sofi
    Lyhagen, Johan
    Lindberg, Inger
    Finch, Tracy
    Åberg, Anna Cristina
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Uppsala universitet.
    The Swedish version of the Normalization Process Theory Measure S-NoMAD: translation, adaptation, and pilot testing2018Ingår i: Implementation Science, ISSN 1748-5908, E-ISSN 1748-5908, Vol. 13, nr 1, artikel-id 146Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: The original British instrument the Normalization Process Theory Measure (NoMAD) is based on the four core constructs of the Normalization Process Theory: Coherence, Cognitive Participation, Collective Action, and Reflexive Monitoring. They represent ways of thinking about implementation and are focused on how interventions can become part of everyday practice.

    AIM: To translate and adapt the original NoMAD into the Swedish version S-NoMAD and to evaluate its psychometric properties based on a pilot test in a health care context including in-hospital, primary, and community care contexts.

    METHODS: A systematic approach with a four-step process was utilized, including forward and backward translation and expert reviews for the test and improvement of content validity of the S-NoMAD in different stages of development. The final S-NoMAD version was then used for process evaluation in a pilot study aimed at the implementation of a new working method for individualized care planning. The pilot was executed in two hospitals, four health care centres, and two municipalities in a region in northern Sweden. The S-NoMAD pilot results were analysed for validity using confirmatory factor analysis, i.e. a one-factor model fitted for each of the four constructs of the S-NoMAD. Cronbach's alpha was used to ascertain the internal consistency reliability.

    RESULTS: In the pilot, S-NoMAD data were collected from 144 individuals who were different health care professionals or managers. The initial factor analysis model showed good fit for two of the constructs (Coherence and Cognitive Participation) and unsatisfactory fit for the remaining two (Collective Action and Reflexive Monitoring) based on three items. Deleting those items from the model yielded a good fit and good internal consistency (alphas between 0.78 and 0.83). However, the estimation of correlations between the factors showed that the factor Reflexive Monitoring was highly correlated (around 0.9) with the factors Coherence and Collective Action.

    CONCLUSIONS: The results show initial satisfactory psychometric properties for the translation and first validation of the S-NoMAD. However, development of a highly valid and reliable instrument is an iterative process, requiring more extensive validation in various settings and populations. Thus, in order to establish the validity and reliability of the S-NoMAD, additional psychometric testing is needed.

  • 85.
    Eriksson, Ellinor
    et al.
    Högskolan Dalarna, Akademin Hälsa och samhälle, Medicinsk vetenskap.
    Ors, Malin
    Högskolan Dalarna, Akademin Hälsa och samhälle, Medicinsk vetenskap.
    Kvinnors upplevelser, samt stödet från sjukvården, tiden efter en hjärtinfarkt: En systematisk litteraturstudie2009Självständigt arbete på grundnivå (kandidatexamen)Studentuppsats (Examensarbete)
    Abstract [sv]

    Syftet med denna litteraturstudie var att belysa kvinnors upplevelser, samt stödet från sjukvården, tiden efter en hjärtinfarkt. Metoden var en systematisk litteraturstudie med granskning av kvalitativa vetenskapliga artiklar. All artikelsökning gjordes via sökmotorn ELIN@dalarna. Artiklarna var etiskt godkända samt publicerade mellan åren 2000-2009 samt skrivna på engelska. De granskades därefter med hjälp av en granskningsmall för kvalitativa artiklar. Resultatet visade i flertalet av studierna att kvinnorna upplevde rädsla, ångest samt stor trötthet efter sin hjärtinfarkt. Andra faktorer som framkom var kvinnornas behov av ändrad livsstil samt mer kvalitetstid med nära och kära. Det framkom även i flera av studierna att kvinnorna som gick till stödgrupper, med andra personer som genomgått en hjärtinfarkt, tyckte att detta var ett stort stöd i deras väg tillbaka efter sjukdomen. Stödet från anhöriga med både praktisk hjälp och psykosocialt stöd var även det en viktig faktor i kvinnornas liv tiden efter hjärtinfarkten.

  • 86. Eriksson, Gunilla
    et al.
    Aasnes, Monica
    Tistad, Malin
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Guidetti, Susanne
    von Koch, Lena
    Occupational gaps in everyday life one year after stroke: association with life satisfaction and impact of stroke2012Ingår i: Topics in Stroke Rehabilitation, ISSN 1074-9357, E-ISSN 1945-5119, Vol. 19, nr 3, s. 244-255Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose: To examine the presence, frequency, and distribution of occupational gaps and to explore whether there are associations between occupational gaps and life satisfaction, self-rated recovery, and functioning and participation in activities of daily living (ADLs) 1 year after stroke.

    Method: Data were collected at onset and at 12 months after stroke from 161 patients admitted to a stroke unit in central Sweden by using Occupational Gaps Questionnaire, LiSat-11, Stroke Impact Scale, Katz ADL Index, and Barthel Index. Spearman rank correlation and Mann Whitney U test were used in the analyses.

    Results: Occupational gaps were reported by 87% of the participants. The number of occupational gaps was moderately associated with participation and self-rated recovery. There was a significant difference in the number of occupational gaps between the participants who were independent in ADLs and those who were not, both at baseline and at 12 months after stroke. There was, however, no significant association between occupational gaps and life satisfaction.

    Conclusions: Occupational gaps 1 year after stroke are very common, particularly among individuals experiencing difficulties in ADLs. Increased efforts are vital to enable individuals to do the activities that are important to them, irrespective of whether these are instrumental ADLs or leisure or social activities. Occupational gaps could be reduced by developing rehabilitation interventions that enable desired activities in different contexts that are crucial for individual patients.

  • 87. Eriksson, Ronnie
    et al.
    Jobs, Magnus
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Ekstrand, Charlotta
    Ullberg, Måns
    Hermann, Björn
    Landegren, Ulf
    Nilsson, Mats
    Blomberg, Jonas
    Multiplex and quantifiable detection of nucleic acid from pathogenic fungi using padlock probes, generic real-time PCR and specific suspension array readout2009Ingår i: Journal of Microbiological Methods, ISSN 0167-7012, E-ISSN 1872-8359, Vol. 78, nr 2, s. 195-202Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A new concept for multiplex detection and quantification of microbes is here demonstrated on a range of infectious fungal species. Padlock probe methodology in conjunction with qPCR and Luminex™ technology was used for simultaneous detection of ten fungal species in one single experiment. By combining the multiplexing properties of padlock probes and Luminex™ detection with the well established quantitative characteristics of qPCR, quantitative microbe detection was done in 10-plex mode. A padlock probe is an oligonucleotide that via a ligation reaction forms circular DNA when hybridizing to specific target DNA. The region of the padlock probe that does not participate in target DNA hybridization contains generic primer sequences for amplification and a tag sequence for Luminex™ detection. This was the fundament for well performing multiplexing. Circularized padlock probes were initially amplified by rolling circle amplification (RCA), followed by a SybrGreen™ real time PCR which allowed an additive quantitative assessment of target DNA in the sample. Detection and quantification of amplified padlock probes were then done on color coded Luminex™ microspheres carrying anti-tag sequences. A novel technique, using labeled oligonucleotides to prevent reannealing of amplimers by covering the flanks of the address sequence, improved the signal to noise ratio in the detection step considerably. The method correctly detected fungi in a variety of clinical samples and offered quantitative information on fungal nucleic acid.

  • 88. Fall, T
    et al.
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Berne, C
    Ingelsson, E
    The role of obesity-related genetic loci in insulin sensitivity2012Ingår i: Diabetic Medicine, ISSN 0742-3071, E-ISSN 1464-5491, Vol. 29, nr 7, s. e62-e66Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aims. Despite rapid advancements and many new diabetes susceptibility loci found in the past few years, few genetic variants associated with insulin sensitivity have been described, potentially attributable to the lack of larger cohorts examined with gold standard methods for insulin sensitivity assessment. There is a strong link between obesity and insulin sensitivity, and we hypothesized that known obesity susceptibility loci may act via effects on insulin sensitivity.

    Methods. A cohort of 71-year-old men without diabetes (Uppsala Longitudinal Study of Adult Men) underwent a euglycaemic-hyperinsulinaemic clamp and genotyping for genetic variants representing 32 loci recently reported to be associated with BMI (n = 926). The effect of these loci on the insulin sensitivity index (M/I ratio) was examined using linear regression.. An in silico replication was performed in publically available data for the three top single-nucleotide polymorphisms from the Meta-Analyses of Glucose and Insulin-related traits Consortium analyses of homeostasis model assessment of insulin resistance (n = 37 037).

    Results. Three loci (SH2B1, MTCH2 and NEGR1) were associated with decreased insulin sensitivity at a nominal significance (P ≤ 0.05) after adjustment for BMI, but did not hold for multiple comparison correction. SH2B1 rs7359397 was also associated with homeostasis model assessment of insulin resistance in the Meta-Analyses of Glucose and Insulin-related traits Consortium data set (P = 3.9 × 10(-3) ).

    Conclusions. Our study supports earlier reports of SH2B1 to be of importance in insulin sensitivity and, in addition, suggests potential roles of NEGR1 and MTCH2. 

  • 89. Fall, Tove
    et al.
    Shiue, Ivy
    Bergeå Af Geijerstam, Per
    Sundström, Johan
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Larsson, Anders
    Melhus, Håkan
    Lind, Lars
    Ingelsson, Erik
    Relations of circulating vitamin D concentrations with left ventricular geometry and function2012Ingår i: European Journal of Heart Failure, ISSN 1388-9842, E-ISSN 1879-0844, Vol. 14, nr 9, s. 985-991Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    AIMS: Vitamin D deficiency has been associated with risk of overt cardiovascular disease (CVD), but associations with subclinical disease are not well characterized. Hence, we examined associations of circulating vitamin D concentrations and left ventricular (LV) geometry and function by echocardiography at baseline and after 5 years in a community-based study.

    METHODS AND RESULTS: In the PIVUS study, we measured serum 25-dihydroxyvitamin-D (25-OH D) at age 70 and performed echocardiography including LV mass, wall thickness, end-diastolic diameter, end-systolic diameter (LVESD), left atrial diameter, fractional shortening, ejection fraction, isovolumic relaxation time, and E/A ratio at both age 70 and 75. We included 870 participants (52% women) without prior myocardial infarctions, heart failure, or prevalent valvular disease. After adjusting for potential confounders, 25-OH D at baseline was found to be significantly associated with LVESD, fractional shortening, and ejection fraction (β, -0.42 mm, P = 0.03; β, 0.70%, P = 0.03; and β, 0.91% P = 0.01, respectively), per 1 SD increase in 25-OH D (SD = 20 nmol/L) at baseline. In longitudinal analyses, vitamin D levels at baseline were not significantly associated with change in LV geometry and function after 5 years. CONCLUSION: In our community-based study among the elderly, we found higher circulating vitamin D concentrations to be associated cross-sectionally with better LV systolic function and smaller LVESD at baseline. The association persisted after adjusting for several potential confounders, including cardiovascular risk factors and calcium, phosphate, and parathyroid hormone levels. Randomized clinical trials are needed to establish firmly or refute a causal relationship between vitamin D levels and changes in LV geometry and function.

  • 90. Feigin, Valery L
    et al.
    Abajobir, Amanuel
    Abate, Kalkidan
    Abd-Allah, Foad
    Abdulle, Abdishakur
    Abera, Semaw
    Abyu, Gebre
    Ahmed, Muktar
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Karolinska institutet.
    Vos, Theo
    Global, regional, and national burden of neurological disorders during 1990-2015: a systematic analysis for the Global Burden of Disease Study 20152017Ingår i: Lancet Neurology, ISSN 1474-4422, E-ISSN 1474-4465, Vol. 16, nr 11, s. 877-897Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background

    Comparable data on the global and country-specific burden of neurological disorders and their trends are crucial for health-care planning and resource allocation. The Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study provides such information but does not routinely aggregate results that are of interest to clinicians specialising in neurological conditions. In this systematic analysis, we quantified the global disease burden due to neurological disorders in 2015 and its relationship with country development level.

    Methods

    We estimated global and country-specific prevalence, mortality, disability-adjusted life-years (DALYs), years of life lost (YLLs), and years lived with disability (YLDs) for various neurological disorders that in the GBD classification have been previously spread across multiple disease groupings. The more inclusive grouping of neurological disorders included stroke, meningitis, encephalitis, tetanus, Alzheimer's disease and other dementias, Parkinson's disease, epilepsy, multiple sclerosis, motor neuron disease, migraine, tension-type headache, medication overuse headache, brain and nervous system cancers, and a residual category of other neurological disorders. We also analysed results based on the Socio-demographic Index (SDI), a compound measure of income per capita, education, and fertility, to identify patterns associated with development and how countries fare against expected outcomes relative to their level of development.

    Findings

    Neurological disorders ranked as the leading cause group of DALYs in 2015 (250·7 [95% uncertainty interval (UI) 229·1 to 274·7] million, comprising 10·2% of global DALYs) and the second-leading cause group of deaths (9·4 [9·1 to 9·7] million], comprising 16·8% of global deaths). The most prevalent neurological disorders were tension-type headache (1505·9 [UI 1337·3 to 1681·6 million cases]), migraine (958·8 [872·1 to 1055·6] million), medication overuse headache (58·5 [50·8 to 67·4 million]), and Alzheimer's disease and other dementias (46·0 [40·2 to 52·7 million]). Between 1990 and 2015, the number of deaths from neurological disorders increased by 36·7%, and the number of DALYs by 7·4%. These increases occurred despite decreases in age-standardised rates of death and DALYs of 26·1% and 29·7%, respectively; stroke and communicable neurological disorders were responsible for most of these decreases. Communicable neurological disorders were the largest cause of DALYs in countries with low SDI. Stroke rates were highest at middle levels of SDI and lowest at the highest SDI. Most of the changes in DALY rates of neurological disorders with development were driven by changes in YLLs.

    Interpretation

    Neurological disorders are an important cause of disability and death worldwide. Globally, the burden of neurological disorders has increased substantially over the past 25 years because of expanding population numbers and ageing, despite substantial decreases in mortality rates from stroke and communicable neurological disorders. The number of patients who will need care by clinicians with expertise in neurological conditions will continue to grow in coming decades. Policy makers and health-care providers should be aware of these trends to provide adequate services.

    Funding

    Bill & Melinda Gates Foundation.

  • 91. Feigin, VL
    et al.
    Nichols, E
    Alam, T
    Bannick, MS
    Beghi, E
    Blake, N
    Culpepper, WJ
    Dorsey, ER
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Karolinska institutet.
    Vos, T
    Global, regional, and national burden of neurological disorders, 1990-2016: a systematic analysis for the Global Burden of Disease Study 20162019Ingår i: Lancet Neurology, ISSN 1474-4422, E-ISSN 1474-4465, Vol. 18, nr 5, s. 459-480Artikel i tidskrift (Refereegranskat)
  • 92. Feldreich, T.
    et al.
    Carlsson, A. C.
    Helmersson-Karlqvist, J.
    Risérus, U.
    Larsson, A.
    Lind, L.
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Uppsala universitet.
    Urinary osteopontin predicts incident chronic kidney disease, while plasma osteopontin predicts cardiovascular death in elderly men2017Ingår i: CardioRenal Medicine, ISSN 1664-3828, Vol. 7, nr 3, s. 245-254Artikel i tidskrift (Refereegranskat)
    Abstract [en]

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

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

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

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

  • 93. Fellström, Bengt
    et al.
    Helmersson-Karlqvist, Johanna
    Lind, Lars
    Soveri, Inga
    Wu, Ping-Hsun
    Thulin, Måns
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Uppsala University.
    Larsson, Anders
    Associations Between Apolipoprotein A1, High-Density Lipoprotein Cholesterol, and Urinary Cytokine Levels in Elderly Males and Females2019Ingår i: Journal of Interferon and Cytokine Research, ISSN 1079-9907, E-ISSN 1557-7465Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    There exists a close relationship between cardiovascular diseases and chronic kidney disease. Apolipoprotein A1 and high-density lipoprotein (HDL) cholesterol are widely used as cardiovascular risk markers but they also have anti-inflammatory properties. The aim of this study was to investigate any associations between HDL levels and cytokine levels in urine. We randomly selected 90 urine samples from the Prospective Investigation of the Vasculature in Uppsala Seniors Study (41 males and 49 females). The samples were analyzed with 2 multiplex assays, Multiplex Inflammation I and Cardiovascular II kits (Olink Bioscience, Uppsala, Sweden). We analyzed the correlations between 158 cytokines in urine with apolipoprotein A1, HDL cholesterol, apolipoprotein B, and low-density lipoprotein cholesterol. There were strong correlations for apolipoprotein A1 and HDL cholesterol with individual cytokines. After adjustment for multiplicity testing, there were 33 significant correlations between apolipoprotein A1 and cytokine levels and 14 of these were also significantly correlated with HDL cholesterol. The strongest associations were observed for IL-1α, SPON2, RAGE, PAR-1, TRAIL-R2, IL-4RA, TNFRSF11A, and SCF. A total of 28 out of 33 correlations were negative, indicating a negative relationship between apolipoprotein A1 and urinary cytokines. The study shows a negative correlation between apolipoprotein A1 and HDL cholesterol and urinary cytokine levels. The finding is in agreement with the anti-inflammatory properties of HDL.

  • 94. Fernström, Maria
    et al.
    Tonkonogi, Michail
    Högskolan Dalarna, Akademin Hälsa och samhälle, Medicinsk vetenskap.
    Sahlin, Kent
    Effects of acute and chronic exercise on mitochondrial uncoupling in human skeletal muscle2004Ingår i: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 554, nr 3, s. 755-763Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Mitochondrial proteins such as uncoupling protein 3 (UCP3) and adenine nucleotide translocase (ANT) may mediate back-leakage of protons and serve as uncouplers of oxidative phosphorylation. We hypothesized that UCP3 and ANT increase after prolonged exercise and/or endurance training, resulting in increased uncoupled respiration (UCR). Subjects were investigated with muscle biopsies before and after acute exercise (75 min of cycling at 70% of ) or 6 weeks endurance training. Mitochondria were isolated and respiration measured in the absence (UCR or state 4) and presence of ADP (coupled respiration or state 3). Protein expression of UCP3 and ANT was measured with Western blotting. After endurance training , citrate synthase activity (CS), state 3 respiration and ANT increased by 24, 47, 40 and 95%, respectively (all P< 0.05), whereas UCP3 remained unchanged. When expressed per unit of CS (a marker of mitochondrial volume) UCP3 and UCR decreased by 54% and 18%(P < 0.05). CS increased by 43% after acute exercise and remained elevated after 3 h of recovery (P < 0.05), whereas the other muscle parameters remained unchanged. An intriguing finding was that acute exercise reversibly enhanced the capacity of mitochondria to accumulate Ca2+(P < 0.05) before opening of permeability transition pores. In conclusion, UCP3 protein and UCR decrease after endurance training when related to mitochondrial volume. These changes may prevent excessive basal thermogenesis. Acute exercise enhances mitochondrial resistance to Ca2+ overload but does not influence UCR or protein expression of UCP3 and ANT. The increased Ca2+ resistance may prevent mitochondrial degradation and the mechanism needs to be further explored.

  • 95. Fielding, Roger A.
    et al.
    Kirn, Dylan R.
    Koochek, Afsaneh
    Reid, Kieran F.
    von Berens, Åsa
    Travison, Thomas G.
    Folta, Sara
    Sacheck, Jennifer
    Åberg, Anna Cristina
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Uppsala universitet.
    Cederholm, Tommy
    Effect of nutritional supplementation and structured physical activity on physical function in mobility-limited older adults: results from the VIVE2 study2015Konferensbidrag (Refereegranskat)
  • 96. Fielding, Roger A.
    et al.
    Travison, T. G.
    Kirn, D. R.
    Koochek, A.
    Reid, K. F.
    von Berens, Å.
    Zhu, H.
    Folta, S. C.
    Åberg, Anna Cristina
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Uppsala universitet.
    Cederholm, T.
    Effect of structured physical activity and nutritional supplementation on physical function in mobility-limited older adults: Results from the VIVE2 randomized trial2017Ingår i: The Journal of Nutrition, Health & Aging, ISSN 1279-7707, E-ISSN 1760-4788, Vol. 21, nr 9, s. 936-942Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives

    The interactions between nutritional supplementation and physical activity on changes in physical function among older adults remain unclear. The primary objective of this study was to examine the impact of nutritional supplementation plus structured physical activity on 400M walk capacity in mobility-limited older adults across two sites (Boston, USA and Stockholm, Sweden).

    Design

    All subjects participated in a physical activity program (3x/week for 24 weeks), involving walking, strength, balance, and flexibility exercises. Subjects were randomized to a daily nutritional supplement (150kcal, 20g whey protein, 800 IU vitamin D) or placebo (30kcal, non-nutritive).

    Setting

    Participants were recruited from urban communities at 2 field centers in Boston MA USA and Stockholm SWE.

    Participants

    Mobility-limited (Short Physical Performance Battery (SPPB) ≤9) and vitamin D insufficient (serum 25(OH) D 9 - 24 ng/ml) older adults were recruited for this study.

    Measurements

    Primary outcome was gait speed assessed by the 400M walk. Results: 149 subjects were randomized into the study (mean age=77.5±5.4; female=46.3%; mean SPPB= 7.9±1.2; mean 25(OH)D=18.7±6.4 ng/ml). Adherence across supplement and placebo groups was similar (86% and 88%, respectively), and was also similar across groups for the physical activity intervention (75% and 72%, respectively). Both groups demonstrated an improvement in gait speed with no significant difference between those who received the nutritional supplement compared to the placebo (0.071 and 0.108 m/s, respectively (p=0.06)). Similar effects in physical function were observed using the SPPB. Serum 25(OH)D increased in supplemented group compared to placebo 7.4 ng/ml versus 1.3 ng/ml respectively.

    Conclusion

    Results suggest improved gait speed following physical activity program with no further improvement with added nutritional supplementation.

  • 97.
    Figarska, Sylwia M.
    et al.
    Stanford Univ, Sch Med, Dept Med, Div Cardiovasc Med, 300 Pasteur Dr, Stanford, CA 94305 USA.;Stanford Univ, Stanford Cardiovasc Inst, Stanford, CA 94305 USA..
    Gustafsson, Stefan
    Uppsala Univ, Dept Med Sci, Mol Epidemiol & Sci Life Lab, Uppsala, Sweden..
    Sundstrom, Johan
    Uppsala Univ, Dept Med Sci, Cardiovasc Epidemiol, Uppsala, Sweden.;Uppsala Univ, Uppsala Clin Res Ctr, Uppsala, Sweden..
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Karolinska Institutet.
    Malarstig, Anders
    Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, Stockholm, Sweden.;Pfizer Worldwide Res & Dev, Stockholm, Sweden..
    Elmstahl, Solve
    Lund Univ, Malmo Univ Hosp, Dept Clin Sci, Div Geriatr Med, Lund, Sweden..
    Fall, Tove
    Uppsala Univ, Dept Med Sci, Mol Epidemiol & Sci Life Lab, Uppsala, Sweden..
    Lind, Lars
    Uppsala Univ, Dept Med Sci, Cardiovasc Epidemiol, Uppsala, Sweden..
    Ingelsson, Erik
    Stanford Univ, Sch Med, Dept Med, Div Cardiovasc Med, 300 Pasteur Dr, Stanford, CA 94305 USA.;Stanford Univ, Stanford Cardiovasc Inst, Stanford, CA 94305 USA.;Uppsala Univ, Dept Med Sci, Mol Epidemiol & Sci Life Lab, Uppsala, Sweden..
    Associations of circulating protein levels with lipid fractions in the general population2018Ingår i: Arteriosclerosis, Thrombosis and Vascular Biology, ISSN 1079-5642, E-ISSN 1524-4636, Vol. 38, nr 10, s. 2505-2518Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: Revealing patterns of associations between circulating protein and lipid levels could improve biological understanding of cardiovascular disease (CVD). In this study, we investigated the associations between proteins related to CVD and triglyceride (TG), total cholesterol, LDL (low-density lipoprotein), and HDL (high-density lipoprotein) cholesterol levels in individuals from the general population.

    Approach and Results: We measured plasma protein levels using the Olink ProSeek CVD I or II+III arrays and analyzed 57 proteins available in 3 population-based cohorts: EpiHealth (n=2029; 52% women; median age, 61 years), PIVUS (Prospective Study of the Vasculature in Uppsala Seniors; n=790; 51% women; all aged 70 years), and ULSAM (Uppsala Longitudinal Study of Adult Men; n=551; all men aged 77 years). A discovery analysis was performed in EpiHealth in a regression framework (adjusted for sex, age, body mass index, smoking, glucose levels, systolic blood pressure, blood pressure medication, diabetes mellitus medication, and CVD history), and associations with false discovery rate <0.05 were further tested in PIVUS and ULSAM, where a P value of 0.05 was considered a successful replication (validation false discovery rate of 0.1%). We used summary statistics from a genome-wide association study on each protein biomarker (meta-analysis of EpiHealth, PIVUS, ULSAM, and IMPROVE [Carotid Intima-Media Thickness and IMT-Progression as Predictors of Vascular Events in a High-Risk European Population]) and publicly available data from Global Lipids Genetics Consortium to perform Mendelian randomization analyses to address possible causality of protein levels. Of 57 tested proteins, 42 demonstrated an association with at least 1 lipid fraction; 35 were associated with TG, 15 with total cholesterol, 9 with LDL cholesterol, and 24 with HDL cholesterol. Among these associations, we found KIM-1 (kidney injury molecule-1), TNFR (TNF [tumor necrosis factor] receptor) 1 and 2, TRAIL-R2 (TRAIL [TNF-related apoptosis-inducing ligand] receptor 2), and RETN (resistin) to be associated with all 4 lipid fractions. Further, 15 proteins were related to both TG and HDL cholesterol in a consistent and biologically expected manner, that is, higher TG and lower HDL cholesterol or vice versa. Another common pattern of associations was concomitantly higher TG, total cholesterol, and LDL cholesterol, which is associated with higher CVD risk. We did not find evidence of causal links for protein levels.

    Conclusions: Our comprehensive analysis of plasma proteins and lipid fractions of 3370 individuals from the general population provides new information about lipid metabolism.

  • 98.
    Flynner, Kristina
    et al.
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Hagström Backe, Kerstin
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Innehållsvalidering av den svenska preliminära San Salvadourskalan: En modifierad Delphistudie2018Självständigt arbete på avancerad nivå (magisterexamen), 10 poäng / 15 hpStudentuppsats (Examensarbete)
    Abstract [sv]

    Bakgrund: Smärta är mer vanligt förekommande hos vuxna personer med flerfunktionsnedsättning jämfört med normalbefolkningen. Vuxna personer med flerfunktionsnedsättning är helt beroende av att personer i omgivningen uppmärksammar och kontinuerligt kartlägger deras smärta. Valida och reliabla bedömningsinstrument för smärta på svenska framtagna för vuxna personer med flerfunktionsnedsättning saknas.

    Syfte: Att undersöka innehållsvaliditeten hos den svenska preliminära versionen av San Salvadourskalan för vuxna personer med flerfunktionsnedsättning.

    Metod: I en Delphistudie med två rundor undersöktes innehållsvaliditeten för den svenska preliminära San Salvadourskalan. En enkät skapades och skickades via e-post till tretton experter i kliniskt arbete med vuxna personer med flerfunktionsnedsättning, vilka skattade relevansen av frågor i basfrågeformulär, smärtbedömningsskala samt texten tillhörande skalstegen i den. Item content validity index (I-CVI) beräknades för frågorna och Scale content validity index universal agreement (S-CVI UA) samt Scale content validity index average (S-CVI Ave) beräknades för skalan som helhet.

    Resultat: I-CVI för basfrågor, smärtbedömningsfrågor samt texten tillhörande dess skalsteg låg över 0,78 för flertalet frågor. S-CVI UA låg under 0,80 för alla delar. S-CVI Ave låg lika med eller över 0,90 för alla delar utom för texten i skalstegen i runda två.

    Slutsats: Utifrån experternas skattningar hade frågorna ett övervägande utmärkt I-CVI. Fortsatta studier av skalans innehållsvaliditet behövs för att kunna bedöma om den svenska preliminära San Salvadourskalan kan anses som valid för att bedöma beteenden som kan bero på smärta hos vuxna personer med flerfunktionsnedsättning.

  • 99. Forouzanfar, Mohammad H
    et al.
    Afshin, Ashkan
    Alexander, Lily T
    Anderson, H. Ross
    Bhutta, Zulfiqar
    Biryukov, Stan
    Brauer, Michael
    Burnett, Richard
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Uppsala university.
    Murray, Christopher J. L
    Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: a systematic analysis for the Global Burden of Disease Study 20152016Ingår i: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 388, nr 10053, s. 1659-1724Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background

    The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context.

    Methods

    We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI).

    Findings

    Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6–58·8) of global deaths and 41·2% (39·8–42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa.

    Interpretation

    Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden.

    Funding

    Bill & Melinda Gates Foundation.

  • 100. Forouzanfar, Mohammad H
    et al.
    Alexander, Lily
    Anderson, H. Ross
    Bachman, Victoria F
    Biryukov, Stan
    Brauer, Michael
    Burnett, Richard
    Casey, Daniel
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Murray, Christopher L
    Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks in 188 countries, 1990–2013: a systematic analysis for the Global Burden of Disease Study 20132015Ingår i: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 386, nr 10010, s. 2287-2323Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) is the first of a series of annual updates of the GBD. Risk factor quantification, particularly of modifiable risk factors, can help to identify emerging threats to population health and opportunities for prevention. The GBD 2013 provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution.

    METHODS: Attributable deaths, years of life lost, years lived with disability, and disability-adjusted life-years (DALYs) have been estimated for 79 risks or clusters of risks using the GBD 2010 methods. Risk-outcome pairs meeting explicit evidence criteria were assessed for 188 countries for the period 1990-2013 by age and sex using three inputs: risk exposure, relative risks, and the theoretical minimum risk exposure level (TMREL). Risks are organised into a hierarchy with blocks of behavioural, environmental and occupational, and metabolic risks at the first level of the hierarchy. The next level in the hierarchy includes nine clusters of related risks and two individual risks, with more detail provided at levels 3 and 4 of the hierarchy. Compared with GBD 2010, six new risk factors have been added: handwashing practices, occupational exposure to trichloroethylene, childhood wasting, childhood stunting, unsafe sex, and low glomerular filtration rate. For most risks, data for exposure were synthesised with a Bayesian meta-regression method, DisMod-MR 2.0, or spatial-temporal Gaussian process regression. Relative risks were based on meta-regressions of published cohort and intervention studies. Attributable burden for clusters of risks and all risks combined took into account evidence on the mediation of some risks such as high body-mass index (BMI) through other risks such as high systolic blood pressure and high cholesterol.

    FINDINGS: All risks combined account for 57·2% (95% uncertainty interval [UI] 55·8-58·5) of deaths and 41·6% (40·1-43·0) of DALYs. Risks quantified account for 87·9% (86·5-89·3) of cardiovascular disease DALYs, ranging to a low of 0% for neonatal disorders and neglected tropical diseases and malaria. In terms of global DALYs in 2013, six risks or clusters of risks each caused more than 5% of DALYs: dietary risks accounting for 11·3 million deaths and 241·4 million DALYs, high systolic blood pressure for 10·4 million deaths and 208·1 million DALYs, child and maternal malnutrition for 1·7 million deaths and 176·9 million DALYs, tobacco smoke for 6·1 million deaths and 143·5 million DALYs, air pollution for 5·5 million deaths and 141·5 million DALYs, and high BMI for 4·4 million deaths and 134·0 million DALYs. Risk factor patterns vary across regions and countries and with time. In sub-Saharan Africa, the leading risk factors are child and maternal malnutrition, unsafe sex, and unsafe water, sanitation, and handwashing. In women, in nearly all countries in the Americas, north Africa, and the Middle East, and in many other high-income countries, high BMI is the leading risk factor, with high systolic blood pressure as the leading risk in most of Central and Eastern Europe and south and east Asia. For men, high systolic blood pressure or tobacco use are the leading risks in nearly all high-income countries, in north Africa and the Middle East, Europe, and Asia. For men and women, unsafe sex is the leading risk in a corridor from Kenya to South Africa.

    INTERPRETATION: Behavioural, environmental and occupational, and metabolic risks can explain half of global mortality and more than one-third of global DALYs providing many opportunities for prevention. Of the larger risks, the attributable burden of high BMI has increased in the past 23 years. In view of the prominence of behavioural risk factors, behavioural and social science research on interventions for these risks should be strengthened. Many prevention and primary care policy options are available now to act on key risks.

    FUNDING: Bill & Melinda Gates Foundation.

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