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  • 151.
    Jobs, Elisabeth
    et al.
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Ingelsson, Erik
    Risérus, Ulf
    Nerpin, Elisabet
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Jobs, Magnus
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Sundström, Johan
    Basu, Samar
    Larsson, Anders
    Lind, Lars
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Association between serum cathepsin S and mortality in older adults2011Inngår i: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 306, nr 10, s. 1113-1121Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Context: Experimental data suggest that cathepsin S, a cysteine protease, is involved in the complex pathways leading to cardiovascular disease and cancer. However, prospective data concerning a potential association between circulating cathepsin S levels and mortality are lacking. Objective To investigate associations between circulating cathepsin S levels and mortality in 2 independent cohorts of elderly men and women.

    Design, Setting, and Participants: Prospective study using 2 community-based cohorts, the Uppsala Longitudinal Study of Adult Men (ULSAM; n = 1009; mean age: 71 years; baseline period: 1991-1995; median follow-up: 12.6 years; end of follow-up: 2006) and the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS; n = 987; 50% women; mean age: 70 years; baseline period: 2001-2004; median follow-up: 7.9 years; end of follow-up: 2010). Serum samples were used to measure cathepsin S.

    Main Outcome Measure Total mortality.

    Results: During follow-up, 413 participants died in the ULSAM cohort (incidence rate: 3.59/100 person-years at risk) and 100 participants died in the PIVUS cohort (incidence rate: 1.32/100 person-years at risk). In multivariable Cox regression models adjusted for age, systolic blood pressure, diabetes, smoking status, body mass index, total cholesterol, high-density lipoprotein cholesterol, antihypertensive treatment, lipid-lowering treatment, and history of cardiovascular disease, higher serum cathepsin S was associated with an increased risk for mortality (ULSAM cohort: hazard ratio [HR] for 1-unit increase of cathepsin S, 1.04 [95% CI, 1.01-1.06], P = .009; PIVUS cohort: HR for 1-unit increase of cathepsin S, 1.03 [95% CI, 1.00-1.07], P = .04). In the ULSAM cohort, serum cathepsin S also was associated with cardiovascular mortality (131 deaths; HR for quintile 5 vs quintiles 1-4, 1.62 [95% CI, 1.11-2.37]; P = .01) and cancer mortality (148 deaths; HR for 1-unit increase of cathepsin S, 1.05 [95% CI, 1.01-1.10]; P = .01).

    Conclusions Among elderly individuals in 2 independent cohorts, higher serum cathepsin S levels were associated with increased mortality risk. Additional research is needed to delineate the role of cathepsin S and whether its measurement might have clinical utility.

  • 152.
    Jobs, Elisabeth
    et al.
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Ingelsson, Erik
    Risérus, Ulf
    Nerpin, Elisabet
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Jobs, Magnus
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Sundström, Johan
    Lind, Lars
    Larsson, Anders
    Basu, Samar
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Serum cathepsin S levels independently predicts total- and cardiovascular mortality in elderly men2011Inngår i: European Society of Cardiology Congress 2011, Stockholm, 2011Konferansepaper (Annet vitenskapelig)
  • 153.
    Jobs, Elisabeth
    et al.
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Ingelsson, Erik
    Risérus, Ulf
    Nerpin, Elisabet
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Jobs, Magnus
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Sundström, Johan
    Lind, Lars
    Larsson, Anders
    Basu, Samar
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Serum cathepsin S levels independently predicts total- and cardiovascular mortality in elderly men2010Inngår i: Kardiovaskulära vårmötet, Göteborg, 2010Konferansepaper (Annet vitenskapelig)
  • 154.
    Jobs, Elisabeth
    et al.
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Ingelsson, Erik
    Risérus, Ulf
    Nerpin, Elisabet
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Jobs, Magnus
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Sundström, Johan
    Lind, Lars
    Larsson, Anders
    Basu, Samar
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Serum cathepsin S predicts the risk for mortality in elderly men and women2011Inngår i: Kardiovaskulära vårmötet, Örebro, 2011Konferansepaper (Annet vitenskapelig)
  • 155.
    Jobs, Elisabeth
    et al.
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Ingelsson, Erik
    Risérus, Ulf
    Nerpin, Elisabet
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Jobs, Magnus
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Sundström, Johan
    Lind, Lars
    Larsson, Anders
    Basu, Samar
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Uppsala university.
    Serum cathepsin S predicts the risk for mortality in elderly men and women2011Konferansepaper (Annet vitenskapelig)
  • 156.
    Jobs, Elisabeth
    et al.
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Uppsala university.
    Risérus, U
    Ingelsson, E
    Helmersson, J
    Nerpin, Elisabet
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Jobs, Magnus
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Sundström, J
    Lind, L
    Larsson, A
    Basu, S
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Serum cathepsin S is associated with serum C-reactive protein and interleukin-6 independently of obesity in elderly men2010Inngår i: Journal of Clinical Epidemiology, ISSN 0895-4356, E-ISSN 1878-5921, Vol. 95, nr 9, s. 4460-4464Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: Cathepsin S has been suggested provide a mechanistic link between obesity and atherosclerosis, possibly mediated via adipose tissue-derived inflammation. Previous data have shown an association between circulating cathepsin S and inflammatory markers in the obese, but to date, community-based reports are lacking. Accordingly, we aimed to investigate the association between serum levels of cathepsin S and markers of cytokine-mediated inflammation in a community-based sample, with prespecified subgroup analyses in nonobese participants.

    Methods: Serum cathepsin S, C-reactive protein (CRP), and IL-6 were measured in a community-based cohort of elderly men (Uppsala Longitudinal Study of Adult Men; mean age 71 years, n = 991). CRP and IL-6 were also measured at a reexamination after 7 yr.

    Results: After adjustment for age, body mass index, fasting plasma glucose, diabetes treatment, systolic blood pressure, diastolic blood pressure, hypertension treatment, serum cholesterol, serum high-density lipoprotein cholesterol, prior cardiovascular disease, smoking, and leisure time physical activity, higher cathepsin S was associated with higher CRP (regression coefficient for 1 SD increase, 0.13; 95% confidence interval 0.07–0.19; P < 0.001) and higher serum IL-6 (regression coefficient for 1 SD increase, 0.08; 95% confidence interval 0.01–0.14; P = 0.02). These associations remained similar in normal-weight participants (body mass index <25 kg/m2, n = 375). In longitudinal analyses, higher cathepsin S at baseline was associated with higher serum CRP and IL-6 after 7 yr.

    Conclusions: These results provide additional evidence for the interplay between cathepsin S and inflammatory activity and suggest that this association is present also in normal-weight individuals in the community.

  • 157.
    Jobs, Elisabeth
    et al.
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Risérus, Ulf
    Ingelsson, Erik
    Helmersson, Johanna
    Nerpin, Elisabet
    Jobs, Magnus
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Sundström, Johan
    Lind, Lars
    Larsson, Anders
    Basu, Samar
    Ärnlöv, Johan
    Cathepsin S is independently associated with cytokine mediated inflammation in elderly men2009Inngår i: European Society of Cardiology Congress, Uppsala, 2009Konferansepaper (Annet vitenskapelig)
    Abstract [en]

    Cathepsin S is independently associated with cytokine mediated inflammation in elderly men Conclusion: Higher serum levels of Cathepsin S were independently associated with higher CRP and IL-6 in a community– based sample of elderly men. Our data provides support for the notion that Cathepsin S is involved in inflammatory processes, possibly leading to atherosclerosis and cardiovascular disease. Background: Cathepsin S is a lysosomal protease that has been suggested to play a key role in the development of atherosclerosis and cardiovascular disease by degradation of vascular extracellular matrix. Previous studies have suggested that cathepsin S provides a molecular link between obesity and atherosclerosis, possibly via increased inflammatory activity. Yet, the association between circulating cathepsin S and inflammation markers has not previously been reported in the community. Aim: To investigate the association between plasma levels of cathepsin- S, C-reactive protein (CRP) and Interleukin 6 (IL-6), in the community. Methods: Serum levels of cathepsin S, CRP, IL-6 were measured in frozen samples from the Uppsala Longitudinal Study of Adult Men (ULSAM), a community-based cohort of elderly men (n=999, mean age 71 years). Results: Cross-sectional association between Cathepsin S, CRP and IL-6 at age 70 showed that one standard deviation (SD) higher serum Cathepsin S was significantly associated with 0.14 SD higher serum CRP and 0.07-0.08 SD higher serum IL-6 when adjusting for age, life style factors (body mass index, physic activity and smoking), cardiovascular risk factors (hypertension, dyslipidemia, previous cardiovascular disease and diabetes and smoking), and the combination of all covariates

  • 158.
    Jobs, Elisabeth
    et al.
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Risérus, Ulf
    Ingelsson, Erik
    Sundström, Johan
    Jobs, Magnus
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Nerpin, Elisabet
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Iggman, David
    Basu, Samar
    Larsson, Anders
    Lind, Lars
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Serum cathepsin S is associated with decreased insulin sensitivity and the development of diabetes type 2 in a community-based cohort of elderly men2012Inngår i: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 36, nr 1, s. 163-165Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE. To investigate associations between serum cathepsin S, impaired insulin sensitivity, defective insulin secretion, and diabetes risk in a community-based sample of elderly men without diabetes.

    RESEARCH DESIGN AND METHODS. Serum cathepsin S, insulin sensitivity (euglycaemic-hyperinsulinaemic clamp), and insulin secretion (early insulin response during an oral glucose tolerance test) were measured in 905 participants of the Uppsala Longitudinal Study of Adult Men (mean age, 71 years). Thirty participants developed diabetes during 6 years of follow-up.

    RESULTS. After adjustment for age, anthropometric variables, and inflammatory markers, higher cathepsin S was associated with decreased insulin sensitivity (regression coefficient per SD increase -0.09 [95% CI -0.14 to -0.04], P = 0.001), but no association with early insulin response was found. Moreover, higher cathepsin S was associated with a higher risk for developing diabetes (odds ratio per SD increase 1.48 [1.08-2.01], P = 0.01).

    CONCLUSIONS. Cathepsin S activity appears to be involved in the early dysregulation of glucose and insulin metabolism.

  • 159.
    Jobs, Magnus
    Högskolan Dalarna, Akademin Hälsa och samhälle, Medicinsk vetenskap.
    Broad-spectrum pathogen detection using padlock probes and suspension micro-array technology.2007Inngår i: Fifth annual planet xmap europe 2007, Amsterdam, 2007Konferansepaper (Annet vitenskapelig)
    Abstract [en]

    A technique for multiplex detection of pathogens based on padlock probes and Luminex technology has been developed. Here detection data from a panel of pathogenic fungi is presented. Most nucleic acid based techniques in use for clinical pathogen detection (diagnosis) can reveal one to a few pathogens in each test. Techniques revealing several pathogens at a time are often problematic due to inherent difficulties with multiplex PCR. The padlock probe (PLP) based detection method, presented here, avoids such problems and has potential for developing highly multiplexed assays. A PLP is an oligonucleotide designed to hybridize to a target sequence so that the 5’ and 3’ end of the probe meet with only a nick separating them. A ligase can close the nick, forming a closed DNA circle of the probe. In the case presented here the internal parts of the probe (the parts not participating in target hybridization) have a general PCR primer target region and a DNA address region (tag region). General PCR primers, that are labelled, can amplify circularized probes and the products can be detected in a Luminex™ machine via the address tags.

  • 160.
    Jobs, Magnus
    Högskolan Dalarna, Akademin Hälsa och samhälle, Medicinsk vetenskap.
    Creating Arrays by Centrifugation2002Inngår i: BioTechniques, ISSN 0736-6205, E-ISSN 1940-9818, Vol. 32, nr 6, s. 1322-1329Artikkel i tidsskrift (Fagfellevurdert)
  • 161.
    Jobs, Magnus
    Högskolan Dalarna, Akademin Hälsa och samhälle, Medicinsk vetenskap.
    Dynamic Allele-Specific Hybridisation: A New Method for Scoring Single Nucleotide Polymorphisms.1999Inngår i: Nature Biotechnology, ISSN 1087-0156, E-ISSN 1546-1696, Vol. 17, s. 87-88Artikkel i tidsskrift (Fagfellevurdert)
  • 162.
    Jobs, Magnus
    Högskolan Dalarna, Akademin Hälsa och samhälle, Medicinsk vetenskap.
    Effect of Oligonucleotide Truncation on Single-nucleotide Distinction by Solid Phase Hybridization2002Inngår i: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 74, nr 1, s. 199-202Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Oligonucleotide microarrays are used to analyze target sequences on the basis of differences in hybridization stability between matched and mismatched probe-target duplexes. DNA microarray manufacture via photolithographic synthesis generates a minority of full-length oligonucleotide probes along with a series of 5'-truncated contaminants. In a model experiment, we now investigate the effect of truncated oligonucleotides on the ability to distinguish target sequence variants that differ in a single nucleotide position. A series of oligonucleotides, mixed in proportions simulating stepwise synthetic yields of between 82 and 100%, were bound to a solid support and allowed to hybridize to a target molecule. The extent of hybridization was monitored over a range of temperatures via the fluorescence of a double-strand-specific dye. The discriminatory power of pure oligonucleotide probes was found to be significantly greater than that of a population of truncated probes, but only over a limited temperature interval. We conclude that at optimal temperatures greater oligonucleotide quality can improve the performance of oligonucleotide hybridization microarrays.

  • 163.
    Jobs, Magnus
    Högskolan Dalarna, Akademin Hälsa och samhälle, Medicinsk vetenskap.
    Identification of 167 Polymorphisms in 88 Genes from Candidate Neurodegeneration Pathways1999Inngår i: Gene, ISSN 0378-1119, E-ISSN 1879-0038, Vol. 238, nr 2, s. 315-324Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Catalogs of intra-gene polymorphisms are needed to facilitate wide-ranging candidate gene-based association studies in common complex diseases. With this in mind, we have scanned multiple alignments of expressed sequence tags and of genomic DNA sequences (PCR products from four to eight unrelated individuals) to find polymorphisms in 195 genes putatively involved in neurodegenerative illness (including components of oxidative stress, excitotoxicity, inflammation, apoptosis and aging). This led to the discovery of 167 polymorphisms in 88 genes. These comprised 163 single nucleotide polymorphisms, one insertion/deletion, and three other variations involving more than one base pair. The polymorphisms were distributed in the exons (87), introns (70), and gene flanking regions (10). Of the exonic polymorphisms, 17 would give rise to non-synonymous amino acid substitutions. These findings now provide a valuable resource for association studies in neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease.

  • 164.
    Jobs, Magnus
    Högskolan Dalarna, Akademin Hälsa och samhälle, Medicinsk vetenskap.
    iFRET: An Improved Fluorescence System for DNA Melting Analysis2002Inngår i: Genome Research, ISSN 1088-9051, E-ISSN 1549-5469, Vol. 12, nr 9, s. 1401-1407Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Fluorescence resonance energy transfer (FRET) is a powerful tool for detecting spatial relationships between macromolecules, one use of which is the tracking of DNA hybridization status. The process involves measuring changes in fluorescence as FRET donor and acceptor moieties are brought closer together or moved farther apart as a result of DNA hybridization/denaturation. In the present study, we introduce a new version of FRET, which we term induced FRET (iFRET), that is ideally suited for melting curve analysis. The innovation entails using a double-strand, DNA-specific intercalating dye (e.g., SYBR Green I) as the FRET donor, with a conventional FRET acceptor affixed to one of the DNA molecules. The SNP genotyping technique dynamic allele specific hybridization (DASH) was used as a platform to compare iFRET to two alternative fluorescence strategies, namely, the use of the intercalating dye alone and the use of a standard FRET pair (fluorescein as donor, 6-rhodamine as acceptor). The iFRET configuration combines the advantages of intercalating dyes, such as high signal strengths and low cost, with maintaining the specificity and multiplex potential afforded by traditional FRET detection systems. Consequently, iFRET represents a fresh and attractive schema for monitoring interactions between DNA molecules.

  • 165.
    Jobs, Magnus
    Högskolan Dalarna, Akademin Hälsa och samhälle, Medicinsk vetenskap.
    Latest Advances in SNP Genotyping by Dynamic Allele Specific Hybridization (DASH)2001Inngår i: Genome Sequencing & Biology, Cold Spring Harbour, New York, USA , 2001Konferansepaper (Fagfellevurdert)
  • 166.
    Jobs, Magnus
    Högskolan Dalarna, Akademin Hälsa och samhälle, Medicinsk vetenskap.
    Ongoing Development of Dynamic Allele Specific Hybridization (DASH) for Polymorphism Analysis2001Inngår i: 4th International Meeting on Single Nucleotide polymorphism and Complex Genome Analysis, Stockholm, 2001Konferansepaper (Fagfellevurdert)
  • 167.
    Jobs, Magnus
    Högskolan Dalarna, Akademin Hälsa och samhälle, Medicinsk vetenskap.
    Robust and Accurate Single Nucleotide Polymorphism Genotyoing by Dynamic Allelespecific Hybridization (DASH): Design criteria and Assay Validation2001Inngår i: Genome Research, ISSN 1088-9051, E-ISSN 1549-5469, Vol. 11, nr 1, s. 152-162Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We recently introduced a generic single nucleotide polymorphism (SNP) genotyping method, termed DASH (dynamic allele-specific hybridization), which entails dynamic tracking of probe (oligonucleotide) to target (PCR product) hybridization as reaction temperature is steadily increased. The reliability of DASH and optimal design rules have not been previously reported. We have now evaluated crudely designed DASH assays (sequences unmodified from genomic DNA) for 89 randomly selected and confirmed SNPs. Accurate genotype assignment was achieved for 89% of these worst-case-scenario assays. Failures were determined to be caused by secondary structures in the target molecule, which could be reliably predicted from thermodynamic theory. Improved design rules were thereby established, and these were tested by redesigning six of the failed DASH assays. This involved reengineering PCR primers to eliminate amplified target sequence secondary structures. This sophisticated design strategy led to complete functional recovery of all six assays, implying that SNPs in most if not all sequence contexts can be effectively scored by DASH. Subsequent empirical support for this inference has been evidenced by ~30 failure-free DASH assay designs implemented across a range of ongoing genotyping programs. Structured follow-on studies employed standardized assay conditions, and revealed that assay reproducibility (733 duplicated genotypes, six different assays) was as high as 100%, with an assay accuracy (1200 genotypes, three different assays) that exceeded 99.9%. No post-PCR assay failures were encountered. These findings, along with intrinsic low cost and high flexibility, validate DASH as an effective procedure for SNP genotyping.

  • 168.
    Jobs, Magnus
    Högskolan Dalarna, Akademin Hälsa och samhälle, Medicinsk vetenskap.
    Robust and Accurate Single Nucleotide Polymorphism Genotyping by Dynamic Allele Specific Hybridization (DASH)2001Inngår i: SNP 2000 : Third International Meeting on Single Nucleotide polymorphism and Complex Genome Analysis, Taos, New Mexico, USA, 2001Konferansepaper (Fagfellevurdert)
    Abstract [en]

    Dynamic allele specific hybridization (DASH) [1] is a method for genotyping single nucleotide polymorphisms (SNPs), insertion/deletions (indels), and other subtle sequence variations. Allele discrimination is based upon the detection of stability differences in duplex DNAs (oligonucleotide probes hybridized to PCR product targets) involving fully matched or allelic-mismatched structures. The procedure involves PCR amplification of a short sequence spanning a variant position. One PCR primer is biotinylated allowing subsequent facile affinity (streptavidin) capture of one strand of the PCR product onto a solid support. An unlabelled oligonucleotide probe, complementary to one of the alleles, is then annealed to this target DNA at low temperature in the presence of a double-strand specific intercalating dye. Samples are then steadily heated through a temperature range while continually monitoring fluorescence, i.e., the amount of duplexed probe-target material. A melting temperature profile is thus derived, indicating the presence of perfectly matched or subtly mismatch probe-target duplexes, or a heterozygous mixture of the two. An extensive testing and validation study was performed in order to maximize the utility of DASH. This study involved design and application of DASH assays for 89 randomly selected SNPs. Nonoptimized assay designs (worst-case scenario) resulted in 79 functional assays from which genotypes could be clearly determined. Statistical analysis of many variables in these assays revealed that the presence or absence of secondary structures in the target sequence was a critical factor for DASH performance. By identifying key bases involved in secondary structure formation and then by altering these in the PCR primers, the formation of secondary structure could be minimized. Six of the failed DASH assays were redesigned following this strategy, and full recovery of all six assays was achieved (bestcase scenario). Subsequent replication and method comparison studies demonstrated that DASH achieves a genotyping accuracy better than 99.9%, and a reproducibility of 100%. No post-PCR assay failures have yet been encountered. These findings, along with intrinsic low cost (less than 25c/genotype) and high flexibility, validate DASH as an effective procedure for SNP genotyping.

  • 169.
    Jobs, Magnus
    Högskolan Dalarna, Akademin Hälsa och samhälle, Medicinsk vetenskap.
    SNP association studies in Alzheimer's disease highlight problems for complex disease analysis2001Inngår i: Trends in Genetics, ISSN 0168-9479, Vol. 17, nr 7, s. 407-413Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Genetic linkage and association analyses are two distinct approaches to understanding the genetic etiology of complex disease. Association analysis has become particularly popular in recent times, but the true utility of the strategy remains uncertain. To try to gain better insight into the relevant issues, we have used genetic association analysis to explore the etiology of Alzheimer's disease. Our empirical findings supplement the theoretical debate, illustrating the general doubtfulness of previous positive findings and the limited ability of typical association studies based on candidate genes to discern true medium-sized signals from false positives. Improvements in genotyping technologies and increasing the number of SNPs tested, without sophisticated allowance for all other issues, could simply lead to an unmanageable overload of false-positive signals, themselves obscuring true disease associations

  • 170.
    Jobs, Magnus
    Högskolan Dalarna, Akademin Hälsa och samhälle, Medicinsk vetenskap.
    SNP Genotyping by Dynamic Allele Specific Hybridization (DASH)2001Inngår i: 7th Conference on Methods and Applications of Fluorescence: Spectroscopy, Imaging and Probes, Amsterdam, The Nederlands , 2001Konferansepaper (Fagfellevurdert)
  • 171.
    Jobs, Magnus
    et al.
    Högskolan Dalarna, Akademin Hälsa och samhälle, Medicinsk vetenskap.
    Eriksson, Ronnie
    Blomberg, Jonas
    Multiplex and quantifiable detection of infectious fungi using padlock probes, general qPCR and suspension microarray readout2013Inngår i: Laboratory protocols in fungal biology current methods in fungal biology / [ed] Gupta, Vijai Kumar; Tuohy, Mari, New York: Springer , 2013Kapittel i bok, del av antologi (Annet vitenskapelig)
  • 172. Järnbert-Pettersson, Hans
    et al.
    Vixner, Linda
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Labour pain - poorly analysed and reported: a systematic review2018Inngår i: BMC Pregnancy and Childbirth, ISSN 1471-2393, E-ISSN 1471-2393, Vol. 18, nr 1, artikkel-id 483Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Modelling and analysing repeated measures data, such as women's experiences of pain during labour, is a complex topic. Traditional end-point analyses such as t-tests, ANOVA, or repeated measures [rANOVA] have known disadvantages. Modern and more sophisticated statistical methods such as mixed effect models provide flexibility and are more likely to draw correct conclusions from data. The aim of this study is to study how labour pain is analysed in repeated measures design studies, and to increase awareness of when and why modern statistical methods are suitable with the aim of encouraging their use in preference of traditional methods.

    METHODS: Six databases were searched with the English language as a restriction. Study eligibility criteria included: Original studies published between 1999 and 2016, studying pregnant women in labour with the aim to compare at least two methods for labour pain management, with at least two measurements of labour pain separated by time, and where labour pain was analysed. After deduplication, all records (n = 2800) were screened by one of the authors who excluded ineligible publication types, leaving 737 records remaining for full-text screening. A sample of 309 studies was then randomly selected and screened by both authors.

    RESULTS: Among the 133 (of 309) studies that fulfilled the study eligibility criteria, 7% used mixed effect models, 20% rANOVA, and 73% used end-point analysis to draw conclusions regarding treatment effects for labour pain between groups. The most commonly used end-point analyses to compare groups regarding labour pain were t-tests (57, 43%) and ANOVA (41, 31%). We present a checklist for clinicians to clarify when mixed effect models should be considered as the preferred choice for analysis, in particular when labour pain is measured.

    CONCLUSIONS: Studies that aim to compare methods for labour pain management often use inappropriate statistical methods, and inaccurately report how the statistical analyses were carried out. The statistical methods used in analyses are often based on assumptions that are not fulfilled or described. We recommend that authors, reviewers, and editors pay greater attention to the analysis when designing and publishing studies evaluating methods for pain relief during labour.

  • 173.
    Karlsson, Maria
    et al.
    Högskolan Dalarna, Akademin Hälsa och samhälle, Medicinsk vetenskap.
    Karlsson, Peter
    Högskolan Dalarna, Akademin Hälsa och samhälle, Medicinsk vetenskap.
    Patienters delaktighet i beslut om den egna omvårdnaden på en kirurgavdelning.: En empirisk studie2006Independent thesis Basic level (degree of Bachelor)Oppgave
  • 174. Kassebaum, Nicholas
    et al.
    Bertozzi-Villa, Amelia
    Coggeshall, Megan S
    Shackelford, Katya A
    Steiner, Caitlyn
    Heuton, Kyle R
    Gonzalez-Medina, Diego
    Barber, Ryan
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Uppsala university.
    Lozano, Rafael
    Global, regional, and national levels and causes of maternal mortality during 1990–2013: a systematic analysis for the Global Burden of Disease Study 20132014Inngår i: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 384, nr 9947, s. 980-1004Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: The fifth Millennium Development Goal (MDG 5) established the goal of a 75% reduction in the maternal mortality ratio (MMR; number of maternal deaths per 100 000 livebirths) between 1990 and 2015. We aimed to measure levels and track trends in maternal mortality, the key causes contributing to maternal death, and timing of maternal death with respect to delivery. 

    Methods: We used robust statistical methods including the Cause of Death Ensemble model (CODEm) to analyse a database of data for 7065 site-years and estimate the number of maternal deaths from all causes in 188 countries between 1990 and 2013. We estimated the number of pregnancy-related deaths caused by HIV on the basis of a systematic review of the relative risk of dying during pregnancy for HIV-positive women compared with HIV-negative women. We also estimated the fraction of these deaths aggravated by pregnancy on the basis of a systematic review. To estimate the numbers of maternal deaths due to nine different causes, we identified 61 sources from a systematic review and 943 site-years of vital registration data. We also did a systematic review of reports about the timing of maternal death, identifying 142 sources to use in our analysis. We developed estimates for each country for 1990-2013 using Bayesian meta-regression. We estimated 95% uncertainty intervals (UIs) for all values. 

    Findings: 292 982 (95% UI 261017-327792) maternal deaths occurred in 2013, compared with 376 034 (343483-407574) in 1990. The global annual rate of change in the MMR was -0.3% (-1.1 to 0.6) from 1990 to 2003, and -2.7% (-3.9 to -1.5) from 2003 to 2013, with evidence of continued acceleration. MMRs reduced consistently in south, east, and southeast Asia between 1990 and 2013, but maternal deaths increased in much of sub-Saharan Africa during the 1990s. 2070 (1290-2866) maternal deaths were related to HIV in 2013, 0.4% (-0.2-0.6) of the global total. MMR was highest in the oldest age groups in both 1990 and 2013. In 2013, most deaths occurred intrapartum or postpartum. Causes varied by region and between 1990 and 2013. We recorded substantial variation in the MMR by country in 2013, from 956.8 (685.1-1262.8) in South Sudan to 2.4 (1.6-3.6) in Iceland. 

    Interpretation: Global rates of change suggest that only 16 countries will achieve the MDG 5 target by 2015. Accelerated reductions since the Millennium Declaration in 2000 coincide with increased development assistance for maternal, newborn, and child health. Setting of targets and associated interventions for after 2015 will need careful consideration of regions that are making slow progress, such as west and central Africa.

  • 175. Kassebaum, Nicholas J
    et al.
    Arora, Megha
    Barber, Ryan M
    Bhutta, Zulficar
    Carter, Austin
    Casey, Daniel C
    Charlson, Fiona J
    Coates, Matthew M
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Uppsala university.
    Murray, Christopher J. L
    Global, regional, and national disability-adjusted life-years (DALYs) for 315 diseases and injuries and healthy life expectancy (HALE), 1990-2015: a systematic analysis for the Global Burden of Disease Study 20152016Inngår i: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 388, nr 10053, s. 1603-1658Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background

    Healthy life expectancy (HALE) and disability-adjusted life-years (DALYs) provide summary measures of health across geographies and time that can inform assessments of epidemiological patterns and health system performance, help to prioritise investments in research and development, and monitor progress toward the Sustainable Development Goals (SDGs). We aimed to provide updated HALE and DALYs for geographies worldwide and evaluate how disease burden changes with development.

    Methods

    We used results from the Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015) for all-cause mortality, cause-specific mortality, and non-fatal disease burden to derive HALE and DALYs by sex for 195 countries and territories from 1990 to 2015. We calculated DALYs by summing years of life lost (YLLs) and years of life lived with disability (YLDs) for each geography, age group, sex, and year. We estimated HALE using the Sullivan method, which draws from age-specific death rates and YLDs per capita. We then assessed how observed levels of DALYs and HALE differed from expected trends calculated with the Socio-demographic Index (SDI), a composite indicator constructed from measures of income per capita, average years of schooling, and total fertility rate.

    Findings

    Total global DALYs remained largely unchanged from 1990 to 2015, with decreases in communicable, neonatal, maternal, and nutritional (Group 1) disease DALYs offset by increased DALYs due to non-communicable diseases (NCDs). Much of this epidemiological transition was caused by changes in population growth and ageing, but it was accelerated by widespread improvements in SDI that also correlated strongly with the increasing importance of NCDs. Both total DALYs and age-standardised DALY rates due to most Group 1 causes significantly decreased by 2015, and although total burden climbed for the majority of NCDs, age-standardised DALY rates due to NCDs declined. Nonetheless, age-standardised DALY rates due to several high-burden NCDs (including osteoarthritis, drug use disorders, depression, diabetes, congenital birth defects, and skin, oral, and sense organ diseases) either increased or remained unchanged, leading to increases in their relative ranking in many geographies. From 2005 to 2015, HALE at birth increased by an average of 2·9 years (95% uncertainty interval 2·9–3·0) for men and 3·5 years (3·4–3·7) for women, while HALE at age 65 years improved by 0·85 years (0·78–0·92) and 1·2 years (1·1–1·3), respectively. Rising SDI was associated with consistently higher HALE and a somewhat smaller proportion of life spent with functional health loss; however, rising SDI was related to increases in total disability. Many countries and territories in central America and eastern sub-Saharan Africa had increasingly lower rates of disease burden than expected given their SDI. At the same time, a subset of geographies recorded a growing gap between observed and expected levels of DALYs, a trend driven mainly by rising burden due to war, interpersonal violence, and various NCDs.

    Interpretation

    Health is improving globally, but this means more populations are spending more time with functional health loss, an absolute expansion of morbidity. The proportion of life spent in ill health decreases somewhat with increasing SDI, a relative compression of morbidity, which supports continued efforts to elevate personal income, improve education, and limit fertility. Our analysis of DALYs and HALE and their relationship to SDI represents a robust framework on which to benchmark geography-specific health performance and SDG progress. Country-specific drivers of disease burden, particularly for causes with higher-than-expected DALYs, should inform financial and research investments, prevention efforts, health policies, and health system improvement initiatives for all countries along the development continuum.

    Funding

    Bill & Melinda Gates Foundation

  • 176. Kassebaum, Nicholas J
    et al.
    Barber, Ryan M
    Bhutta, Zulfiqar
    Dandona, Lalit
    Gething, Peter W
    Hay, Simon I
    Kinfu, Yohannes
    Larson, Heidi J
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Uppsala university.
    Remuzzi, Giuseppe
    Global, regional, and national levels of maternal mortality, 1990-2015: a systematic analysis for the Global Burden of Disease Study 20152016Inngår i: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 388, nr 10053, s. 1775-1812Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background

    In transitioning from the Millennium Development Goal to the Sustainable Development Goal era, it is imperative to comprehensively assess progress toward reducing maternal mortality to identify areas of success, remaining challenges, and frame policy discussions. We aimed to quantify maternal mortality throughout the world by underlying cause and age from 1990 to 2015.

    Methods

    We estimated maternal mortality at the global, regional, and national levels from 1990 to 2015 for ages 10–54 years by systematically compiling and processing all available data sources from 186 of 195 countries and territories, 11 of which were analysed at the subnational level. We quantified eight underlying causes of maternal death and four timing categories, improving estimation methods since GBD 2013 for adult all-cause mortality, HIV-related maternal mortality, and late maternal death. Secondary analyses then allowed systematic examination of drivers of trends, including the relation between maternal mortality and coverage of specific reproductive health-care services as well as assessment of observed versus expected maternal mortality as a function of Socio-demographic Index (SDI), a summary indicator derived from measures of income per capita, educational attainment, and fertility.

    Findings

    Only ten countries achieved MDG 5, but 122 of 195 countries have already met SDG 3.1. Geographical disparities widened between 1990 and 2015 and, in 2015, 24 countries still had a maternal mortality ratio greater than 400. The proportion of all maternal deaths occurring in the bottom two SDI quintiles, where haemorrhage is the dominant cause of maternal death, increased from roughly 68% in 1990 to more than 80% in 2015. The middle SDI quintile improved the most from 1990 to 2015, but also has the most complicated causal profile. Maternal mortality in the highest SDI quintile is mostly due to other direct maternal disorders, indirect maternal disorders, and abortion, ectopic pregnancy, and/or miscarriage. Historical patterns suggest achievement of SDG 3.1 will require 91% coverage of one antenatal care visit, 78% of four antenatal care visits, 81% of in-facility delivery, and 87% of skilled birth attendance.

    Interpretation

    Several challenges to improving reproductive health lie ahead in the SDG era. Countries should establish or renew systems for collection and timely dissemination of health data; expand coverage and improve quality of family planning services, including access to contraception and safe abortion to address high adolescent fertility; invest in improving health system capacity, including coverage of routine reproductive health care and of more advanced obstetric care—including EmOC; adapt health systems and data collection systems to monitor and reverse the increase in indirect, other direct, and late maternal deaths, especially in high SDI locations; and examine their own performance with respect to their SDI level, using that information to formulate strategies to improve performance and ensure optimum reproductive health of their population.

    Funding

    Bill & Melinda Gates Foundation.

  • 177. Kassebaum, Nicholas
    et al.
    Kyu, Hmwe Hmwe
    Zoeckler, Leo
    Olsen, Helen
    Thomas, Katie
    Pinho, Christine
    Bhutta, Zulfiqar
    Dandona, Lalit
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Uppsala universitet.
    Vos, Theo
    Child and adolescent health from 1990 to 2015: Findings from the Global Burden of Diseases, Injuries and Risk Factors 2015 study2017Inngår i: JAMA pediatrics, ISSN 2168-6203, E-ISSN 2168-6211, Vol. 171, nr 6, s. 573-592Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Importance  Comprehensive and timely monitoring of disease burden in all age groups, including children and adolescents, is essential for improving population health.

    Objective  To quantify and describe levels and trends of mortality and nonfatal health outcomes among children and adolescents from 1990 to 2015 to provide a framework for policy discussion.

    Evidence Review  Cause-specific mortality and nonfatal health outcomes were analyzed for 195 countries and territories by age group, sex, and year from 1990 to 2015 using standardized approaches for data processing and statistical modeling, with subsequent analysis of the findings to describe levels and trends across geography and time among children and adolescents 19 years or younger. A composite indicator of income, education, and fertility was developed (Socio-demographic Index [SDI]) for each geographic unit and year, which evaluates the historical association between SDI and health loss.

    Findings  Global child and adolescent mortality decreased from 14.18 million (95% uncertainty interval [UI], 14.09 million to 14.28 million) deaths in 1990 to 7.26 million (95% UI, 7.14 million to 7.39 million) deaths in 2015, but progress has been unevenly distributed. Countries with a lower SDI had a larger proportion of mortality burden (75%) in 2015 than was the case in 1990 (61%). Most deaths in 2015 occurred in South Asia and sub-Saharan Africa. Global trends were driven by reductions in mortality owing to infectious, nutritional, and neonatal disorders, which in the aggregate led to a relative increase in the importance of noncommunicable diseases and injuries in explaining global disease burden. The absolute burden of disability in children and adolescents increased 4.3% (95% UI, 3.1%-5.6%) from 1990 to 2015, with much of the increase owing to population growth and improved survival for children and adolescents to older ages. Other than infectious conditions, many top causes of disability are associated with long-term sequelae of conditions present at birth (eg, neonatal disorders, congenital birth defects, and hemoglobinopathies) and complications of a variety of infections and nutritional deficiencies. Anemia, developmental intellectual disability, hearing loss, epilepsy, and vision loss are important contributors to childhood disability that can arise from multiple causes. Maternal and reproductive health remains a key cause of disease burden in adolescent females, especially in lower-SDI countries. In low-SDI countries, mortality is the primary driver of health loss for children and adolescents, whereas disability predominates in higher-SDI locations; the specific pattern of epidemiological transition varies across diseases and injuries.

    Conclusions and Relevance  Consistent international attention and investment have led to sustained improvements in causes of health loss among children and adolescents in many countries, although progress has been uneven. The persistence of infectious diseases in some countries, coupled with ongoing epidemiologic transition to injuries and noncommunicable diseases, require all countries to carefully evaluate and implement appropriate strategies to maximize the health of their children and adolescents and for the international community to carefully consider which elements of child and adolescent health should be monitored.

  • 178. Kirn, D.R.
    et al.
    Koochek, A.
    Reid, K.F.
    von Berens, Å.
    Travison, T.G.
    Folta, S.
    Sacheck, J.
    Nelson, M.
    Åberg, Anna Cristina
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Uppsala universitet.
    Fielding, R.A.
    The vitality, independence, and vigor in the elderly 2 study (VIVE2): design and methods2015Inngår i: Contemporary Clinical Trials, ISSN 1551-7144, E-ISSN 1559-2030, Vol. 43, s. 164-171Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Nutritional supplementation may potentiate the increase in skeletal muscle protein synthesis following exercise in healthy older individuals. Whether exercise and nutrition act synergistically to produce sustained changes in physical functioning and body composition has not been well studied, particularly in mobility-limited older adults.

    Methods: The VIVE2 study was a multi-center, randomized controlled trial, conducted in the United States and Sweden. This study was designed to compare the effects of a 6-month intervention with a once daily, experimental, 4fl. oz. liquid nutritional supplement providing 150kcal, whey protein (20g), vitamin D (800IU) (Nestlé Health Science, Vevey, Switzerland), to a low calorie placebo drink (30kcal, non-nutritive; identical format) when combined with group-based exercise in 150 community-dwelling, mobility-limited older adults. All participants participated in a structured exercise program (3 sessions/week for 6months), which included aerobic, strength, flexibility, and balance exercises.

    Results: The primary outcome was 6-month change in 400m walk performance (m/s) between supplement and placebo groups. Secondary outcomes included 6month change in: body composition, muscle cross-sectional area, leg strength, grip strength, stair climb time, quality of life, physical performance, mood/depressive symptoms and nutritional status. These outcomes were selected based on their applicability to the health and well-being of older adults.

    Conclusions: The results of this study will further define the role of nutritional supplementation on physical functioning and restoration of skeletal muscle mass in older adults. Additionally, these results will help refine the current physical activity and nutritional recommendations for mobility-limited older adults.

  • 179. Klatte, Derk C F
    et al.
    Gasparini, Alessandro
    Xu, Hong
    de Deco, Pietro
    Trevisan, Marco
    Johansson, Anna L V
    Wettermark, Björn
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Uppsala universitet.
    Janmaat, Cynthia J
    Carrero, Juan J
    Association between proton pump inhibitor use and risk of progression of chronic kidney disease2017Inngår i: Gastroenterology, ISSN 0016-5085, E-ISSN 1528-0012, Vol. 153, nr 3, s. 702-710Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND & AIMS: Proton pump inhibitors (PPI) have been associated with acute kidney injury (AKI) and recent studies suggest that they may be associated with the risk of chronic kidney disease (CKD).

    METHODS: We performed a retrospective analysis using the Stockholm creatinine measurements database, which contains information on diagnoses, dispensation claims, and laboratory test results for all citizens in the Stockholm region from 2007 through 2010. We identified new users of PPIs (n= 105305) and new users of H2 blockers (H2B; n= 9578); data on renal outcomes were collected for a median 2.7 years. The primary outcome was progression CKD, defined as doubling of creatinine or decrease in estimated glomerular filtration rate of 30% or more. Secondary outcomes were end-stage renal disease and acute kidney injury (AKI). Complete collection of repeated PPI and H2B dispensations at pharmacies in Sweden allowed modeling the time-dependent risk associated to cumulative PPI exposure.

    RESULTS: Users of PPIs, compared to users of H2Bs, had an increased risk for doubled levels of creatinine (1985 events; adjusted hazard ratio [HR], 1.26; 95% CI, 1.05-1.51) and decrease in estimated glomerular filtration rate of 30% or more (11045 events; 1.26; 95% CI, 1.16-1.36). PPI use also associated with development of end-stage renal disease (HR, 2.40; 0.76-7.58) and AKI (HR, 1.30; 95% CI, 1.00-1.69). There was a graded association between cumulative exposure to PPIs and risk of CKD progression. This was not the case for cumulative H2B use.

    CONCLUSIONS: Initiation of PPI therapy and cumulative PPI exposure associate with increased risk of CKD progression in a large, North European healthcare system. Although consistent, the association was modest in magnitude, and cannot exclude residual confounding.

  • 180. Koochek, A
    et al.
    von Berens, Å
    Gustafsson, T
    Kirn, D.R
    Laussen, J
    Reid, K.F
    Åberg, Anna Cristina
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Nydahl, M
    Cederholm, T
    Fielding, A
    Serum 25-hydroxy vitamin D and physical performance in community-dwelling old mobility limited adults in Sweden and USA2014Konferansepaper (Fagfellevurdert)
  • 181. Kovesdy, Csaba P
    et al.
    Coresh, Josef
    Ballew, Shoshana H
    Woodward, Mark
    Levin, Adeera
    Naimark, David M J
    Nally, Joseph
    Rothenbacher, Dietrich
    Stengel, Benedicte
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Past Decline Versus Current eGFR and Subsequent ESRD Risk2016Inngår i: Journal of the American Society of Nephrology, ISSN 1046-6673, E-ISSN 1533-3450, Vol. 27, nr 8, s. 2447-2455Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    eGFR is a robust predictor of ESRD risk. However, the prognostic information gained from the past trajectory (slope) beyond that of the current eGFR is unclear. We examined 22 cohorts to determine the association of past slopes and current eGFR level with subsequent ESRD. We modeled hazard ratios as a spline function of slopes, adjusting for demographic variables, eGFR, and comorbidities. We used random effects meta-analyses to combine results across studies stratified by cohort type. We calculated the absolute risk of ESRD at 5 years after the last eGFR using the weighted average baseline risk. Overall, 1,080,223 participants experienced 5163 ESRD events during a mean follow-up of 2.0 years. In CKD cohorts, a slope of -6 versus 0 ml/min per 1.73 m(2) per year over the previous 3 years (a decline of 18 ml/min per 1.73 m(2) versus no decline) associated with an adjusted hazard ratio of ESRD of 2.28 (95% confidence interval, 1.88 to 2.76). In contrast, a current eGFR of 30 versus 50 ml/min per 1.73 m(2) (a difference of 20 ml/min per 1.73 m(2)) associated with an adjusted hazard ratio of 19.9 (95% confidence interval, 13.6 to 29.1). Past decline contributed more to the absolute risk of ESRD at lower than higher levels of current eGFR. In conclusion, during a follow-up of 2 years, current eGFR associates more strongly with future ESRD risk than the magnitude of past eGFR decline, but both contribute substantially to the risk of ESRD, especially at eGFR<30 ml/min per 1.73 m(2).

  • 182. Kyu, Hmwe Hmwe
    et al.
    Abate, Degu
    Abate, Kalkidan Hassen
    Abay, Solomon
    Abbafati, Cristiana
    Abbasi, Nooshin
    Abbastabar, Hedayat
    Abd-Allah, Foad
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Karolinska institutet.
    Murray, Christopher J. L
    Global, regional, and national disability-adjusted life-years (DALYs) for 359 diseases and injuries and healthy life expectancy (HALE) for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 20172018Inngår i: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 392, nr 10159, s. 1859-1922Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background How long one lives, how many years of life are spent in good and poor health, and how the population's state of health and leading causes of disability change over time all have implications for policy, planning, and provision of services. We comparatively assessed the patterns and trends of healthy life expectancy (HALE), which quantifies the number of years of life expected to be lived in good health, and the complementary measure of disability-adjusted life years (DALYs), a composite measure of disease burden capturing both premature mortality and prevalence and severity of ill health, for 359 diseases and injuries for 195 countries and territories over the past 28 years. 

    Methods We used data for age-specific mortality rates, years of life lost (YLLs) due to premature mortality, and years lived with disability (YLDs) from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 to calculate HALE and DALYs from 1990 to 2017. We calculated HALE using age-specific mortality rates and YLDs per capita for each location, age, sex, and year. We calculated DALYs for 359 causes as the sum of YLLs and YLDs. We assessed how observed HALE and DALYs differed by country and sex from expected trends based on Sociodemographic Index (SDI). We also analysed HALE by decomposing years of life gained into years spent in good health and in poor health, between 1990 and 2017, and extra years lived by females compared with males. 

    Findings Globally, from 1990 to 2017, life expectancy at birth increased by 7.4 years (95% uncertainty interval 74-7.8), from 65.6 years (65.3-65- 8) in 1990 to 73.0 years (72.7-73.3) in 2017. The increase in years of life varied from 5.1 years (5.0-5.3) in high SDI countries to 12.0 years (11.3-12.8) in low SDI countries. Of the additional years of life expected at birth, 26.3% (20.1-33.1) were expected to be spent in poor health in high SDI countries compared with 11.7% (8.8-15.1) in low-middle SDI countries. HALE at birth increased by 6.3 years (5.9-6.7), from 57.0 years (54.6-59.1) in 1990 to 63.3 years (60.5-65.7) in 2017. The increase varied from 3.8 years (3.4-4.1) in high SDI countries to 10.5 years (9.8-11.2) in low SDI countries. Even larger variations in HALE than these were observed between countries, ranging from 1.0 year (0.4-1.7) in Saint Vincent and the Grenadines (62.4 years [59.9-64.7] in 1990 to 63.5 years [60.9-65.8] in 2017) to 23.7 years (21.9-25.6) in Eritrea (30.7 years [28.9-32.2] in 1990 to 54.4 years [51.5-57.1] in 2017). In most countries, the increase in HALE was smaller than the increase in overall life expectancy, indicating more years lived in poor health. In 180 of 195 countries and territories, females were expected to live longer than males in 2017, with extra years lived varying from 1.4 years (0.6-2.3) in Algeria to 11.9 years (10.9-12.9) in Ukraine. Of the extra years gained, the proportion spent in poor health varied largely across countries, with less than 20% of additional years spent in poor health in Bosnia and Herzegovina, Burundi, and Slovakia, whereas in Bahrain all the extra years were spent in poor health. In 2017, the highest estimate of HALE at birth was in Singapore for both females (75.8 years [72.4-78.7]) and males (72.6 years [69 " 8-75.0]) and the lowest estimates were in Central African Republic (47.0 years [43.7-50.2] for females and 42.8 years [40.1-45.6] for males). Globally, in 2017, the five leading causes of DALYs were neonatal disorders, ischaemic heart disease, stroke, lower respiratory infections, and chronic obstructive pulmonary disease. Between 1990 and 2017, age-standardised DALY rates decreased by 41.3% (38.8-43.5) for communicable diseases and by 49"8% (47.9-51.6) for neonatal disorders. For non-communicable diseases, global DALYs increased by 40.1% (36.8-43.0), although age-standardised DALY rates decreased by 18.1% (16.0-20.2). 

    Interpretation With increasing life expectancy in most countries, the question of whether the additional years of life gained are spent in good health or poor health has been increasingly relevant because of the potential policy implications, such as health-care provisions and extending retirement ages. In some locations, a large proportion of those additional years are spent in poor health. Large inequalities in HALE and disease burden exist across countries in different SDI quintiles and between sexes. The burden of disabling conditions has serious implications for health system planning and health-related expenditures. Despite the progress made in reducing the burden of communicable diseases and neonatal disorders in low S DI countries, the speed of this progress could be increased by scaling up proven interventions. The global trends among non-communicable diseases indicate that more effort is needed to maximise HALE, such as risk prevention and attention to upstream determinants of health.

  • 183. Lagali, Neil S
    et al.
    Badian, Reza A
    Liu, Xu
    Feldreich, Tobias R
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Karolinska institutet.
    Utheim, Tor Paaske
    Dahlin, Lars B
    Rolandsson, Olov
    Dendritic cell maturation in the corneal epithelium with onset of type 2 diabetes is associated with tumor necrosis factor receptor superfamily member 92018Inngår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, nr 1, artikkel-id 14248Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Type 2 diabetes mellitus is characterized by a low-grade inflammation; however, mechanisms leading to this inflammation in specific tissues are not well understood. The eye can be affected by diabetes; thus, we hypothesized that inflammatory changes in the eye may parallel the inflammation that develops with diabetes. Here, we developed a non-invasive means to monitor the status of inflammatory dendritic cell (DC) subsets in the corneal epithelium as a potential biomarker for the onset of inflammation in type 2 diabetes. In an age-matched cohort of 81 individuals with normal and impaired glucose tolerance and type 2 diabetes, DCs were quantified from wide-area maps of the corneal epithelial sub-basal plexus, obtained using clinical in vivo confocal microscopy (IVCM). With the onset of diabetes, the proportion of mature, antigen-presenting DCs increased and became organized in clusters. Out of 92 plasma proteins analysed in the cohort, tumor necrosis factor receptor super family member 9 (TNFRSF9) was associated with the observed maturation of DCs from an immature to mature antigen-presenting phenotype. A low-grade ocular surface inflammation observed in this study, where resident immature dendritic cells are transformed into mature antigen-presenting cells in the corneal epithelium, is a process putatively associated with TNFRSF9 signalling and may occur early in the development of type 2 diabetes. IVCM enables this process to be monitored non-invasively in the eye.

  • 184. Larsson, A.
    et al.
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Rydén, I.
    Helmersson-Karlqvist, J.
    Lind, L.
    Associations between cathepsin B and inflammation markers in elderly males and females2015Inngår i: Horizons in World Cardiovascular Research, Nova Science Publishers, Inc., 2015, Vol. 8, s. 157-164Kapittel i bok, del av antologi (Fagfellevurdert)
    Abstract [en]

    Background: The association between cathepsin B and inflammatory disorders is being increasingly recognized, but the underlying mechanism is less understood. The aim of the present study was to study the association between cathepsin B and different inflammation markers in a community-based cohort of elderly males and females.

    Methods: Blood samples were collected from 729 individuals in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) cohort at the age of 75 years. Cathepsin B and the inflammation markers CRP, Pentraxin 3, TNF receptor 1 and TNF receptor 2 were analyzed together with albumin, cholesterol, HDL-cholesterol, LDL-cholesterol, cholesterol, apolipoprotein A1, apolipoprotein B and triglycerides.

    Results: Cathepsin B was significantly associated with TNF receptor 1 and 2 (P<0.001) but not with CRP and pentraxin 3. There were also significant associations with cholesterol, LDL and apolipoprotein B.

    Conclusion: The type of inflammatory response is of importance for circulating cathepsin B. The association between cathepsin B and the cardiovascular risk markers cholesterol, LDL-cholesterol and apolipoprotein B could contribute to plaque destabilisation and ruptures by cathepsin B.

  • 185.
    Larsson, Catarina
    et al.
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Lovén, Jessica
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Multimodal smärtrehabilitering i specialistvård: En kartläggning av fysioterapeutiska interventioner2018Independent thesis Advanced level (degree of Master (One Year)), 10 poäng / 15 hpOppgave
    Abstract [sv]

    Bakgrund: Långvarig smärta har konsekvenser på såväl individ- som samhällsnivå och är ett stort folkhälsoproblem. Forskning har visat måttligt till starkt vetenskapligt stöd för multimodal rehabilitering (MMR) vid komplex smärtproblematik. Vad fysioterapeuten använder för åtgärder inom MMR och hur samarbetet med andra yrkeskategorier ser ut finns dåligt beskrivet.

    Syfte: Att kartlägga fysioterapeutens arbete inom ramen för multimodal smärtrehabilitering inom specialistvården (MMR2).

    Metod: Webbenkätstudie där data samlades in från 71 fysioterapeuter som arbetade på enheter anslutna till Nationella registret över smärtrehabilitering (NRS).

    Resultat: Fysioterapeuternas arbete bestod framförallt av undervisning/råd och olika former av träning. Strategier för beteendeförändring, övningar i medveten närvaro/kroppsmedvetenhet och hemövningar var andra vanliga åtgärder. Acceptance and Commitment Therapy (ACT) och Kognitiv beteendeterapi (KBT) användes i flera moment av rehabiliteringen på många enheter. Rehabilitering i grupp var vanligast med aktiva åtgärder som till exempel träning. Rehabiliteringsperioden var vanligen 8-11 veckor, under vilken patienten träffade en fysioterapeut flera gånger i veckan. Teamen hade ett tätt samarbete med regelbundna teamträffar, uppföljningar och gemensamma åtgärder.

    Slutsats: Fysioterapeutens arbete inom MMR2 utgår från ett biopsykosocialt perspektiv där tyngdpunkten ligger i att återställa och/eller förbättra kroppsfunktion. Fysioterapeuterna har bred kompetens och lång erfarenhet vilket möjliggör att deras kunskaper om kroppen och rörelsesystemet kan integreras med åtgärder för beteendeförändring. Tillsammans med övriga yrkeskategorier täcker fysioterapeutens arbete in alla domäner i Klassifikation av funktionstillstånd, funktionshinder och hälsa (ICF). För en ökad förståelse kring vad som styr valet av fysioterapeutiska åtgärder inom MMR2 och hur arbetet med dessa åtgärder ser ut i den kliniska vardagen behövs fortsatt forskning.

  • 186. Larsson, T
    et al.
    Olauson, H
    Hagström, E
    Ingelsson, E
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Lind, L
    Sundström, J
    Conjoint effects of serum calcium and phosphate on risk of total, cardiovascular, and noncardiovascular mortality in the community2010Inngår i: Arteriosclerosis, Thrombosis and Vascular Biology, ISSN 1079-5642, E-ISSN 1524-4636, Vol. 30, nr 2, s. 333-U379Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: Hyperphosphatemia is a cardiovascular risk factor in patients with chronic kidney disease. Relations of circulating calcium (Ca) and phosphorus (Pi) to long-term mortality risk in the community require further investigation. 

    Methods and Results: Associations of serum Ca and Pi to mortality were evaluated in a community-based cohort of 2176 men (mean age, 50.1 years). During follow-up (median, 29.8 years), 1009 men died, and 466 of these deaths resulted from cardiovascular causes. In Cox proportional hazards models, serum Pi and [CaxPi] were independent predictors of total mortality (hazard ratio per SD, 1.06; 95% CI, 1.01-1.12; P=0.03; 1.07; 95% CI, 1.01-1.12; P=0.01) and cardiovascular mortality (1.10; 95% CI, 1.02-1.18; P=0.01; 1.10; 95% CI, 1.03-1.19; P=0.008). Serum Ca was associated with risk of total mortality (1.08; 95% CI, 1.01-1.16; P=0.02) and noncardiovascular mortality (1.10; 95% CI, 1.01-1.21; P=0.04). Results were consistent after multivariate adjustments in subsamples of individuals with estimated glomerular filtration rate > 90 mL/min and low-to-normal serum Ca and Pi. 

    Conclusion: Circulating Ca and Pi levels are associated with risks of total, cardiovascular, and noncardiovascular mortality in the community, and their conjoint effects are additive. Additional studies are warranted to evaluate whether Ca and Pi are modifiable risk factors in the general population. (Arterioscler Thromb Vasc Biol. 2010;30:333-339.)

  • 187. Leavy, Breiffni
    et al.
    Byberg, Lisa
    Michaelsson, Karl
    Melhus, Håkan
    Åberg, Anna Cristina
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Uppsala universitet.
    The fall descriptions and health characteristics of older adults with hip fracture: a mixed methods study2015Inngår i: BMC Geriatrics, ISSN 1471-2318, E-ISSN 1471-2318, Vol. 15, artikkel-id 40Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: In light of the multifactorial etiology of fall-related hip fracture, knowledge of fall circumstances may be especially valuable when placed in the context of the health of the person who falls. We aimed to investigate the circumstances surrounding fall-related hip fractures and to describe fall circumstances in relation to participants' health and functional characteristics.

    Methods: The fall circumstances of 125 individuals (age >= 50 years) with hip fracture were investigated using semi-structured interviews. Data concerning participants' health (comorbidities and medications) and function (self-reported performance of mobility, balance, personal activities of daily living and physical activity, previous falls and hand grip strength) were collected via medical records, questionnaires and dynamometry. Using a mixed methods design, both data sets were analysed separately and then merged in order to provide a comprehensive description of fall events and identify eventual patterns in the data.

    Results: Fall circumstances were described as i) Activity at the time of the fall: Positional change (n = 24, 19%); Standing (n = 16, 13%); Walking (n = 71, 57%); Balance challenging (n = 14, 11%) and ii) Nature of the fall: Environmental (n = 32, 26%); Physiological (n = 35, 28%); Activity-related indoor (n = 8, 6%) and outdoor (n = 8, 6%); Trips and slips on snow (n = 20, 16%) and in snow-free conditions (n = 12, 10%) and Unknown (n = 10, 8%). We observed the following patterns regarding fall circumstances and participants' health: those who fell i) during positional change had the poorest functional status; ii) due to environmental reasons (indoors) had moderate physical function, but high levels of comorbidity and fall risk increasing medications; iii) in snow-free environments (outdoors) appeared to have a poorer health and functional status than other outdoor groups.

    Conclusions: Our findings indicate that patterns exist in relation to the falls circumstances and health characteristics of people with hip fracture which build upon that previously reported. These patterns, when verified, can provide useful information as to the ways in which fall prevention strategies can be tailored to individuals of varying levels of health and function who are at risk for falls and hip fracture.

  • 188. Leavy, Breiffni
    et al.
    Michaëlsson, Karl
    Åberg, Anna Cristina
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Melhus, Håkan
    Byberg, Liisa
    The impact of disease and drugs on hip fracture risk2017Inngår i: Calcified Tissue International, ISSN 0171-967X, E-ISSN 1432-0827, Vol. 100, nr 1, s. 1-12Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We report the risks of a comprehensive range of disease and drug categories on hip fracture occurrence using a strict population-based cohort design. Participants included the source population of a Swedish county, aged ≥50 years (n = 117,494) including all incident hip fractures during 1 year (n = 477). The outcome was hospitalization for hip fracture (ICD-10 codes S72.0-S72.2) during 1 year (2009-2010). Exposures included: prevalence of (1) inpatient diseases [International Classification of Diseases (ICD) codes A00-T98 in the National Patient Register 1987-2010] and (2) prescribed drugs dispensed in 2010 or the year prior to fracture. We present age- and sex-standardized risk ratios (RRs), risk differences (RDs) and population attributable risks (PARs) of disease and drug categories in relation to hip fracture risk. All disease categories were associated with increased risk of hip fracture. Largest risk ratios and differences were for mental and behavioral disorders, diseases of the blood and previous fracture (RRs between 2.44 and 3.00; RDs (per 1000 person-years) between 5.0 and 6.9). For specific drugs, strongest associations were seen for antiparkinson (RR 2.32 [95 % CI 1.48-1.65]; RD 5.2 [1.1-9.4]) and antidepressive drugs (RR 1.90 [1.55-2.32]; RD 3.1 [2.0-4.3]). Being prescribed ≥10 drugs during 1 year incurred an increased risk of hip fracture, whereas prescription of cardiovascular drugs or ≤5 drugs did not appear to increase risk. Diseases inferring the greatest PARs included: cardiovascular diseases PAR 22 % (95 % CI 14-29) and previous injuries (PAR 21 % [95 % CI 16-25]; for specific drugs, antidepressants posed the greatest risk (PAR 16 % [95 % CI 12.0-19.3]).

  • 189. LeBlanc, Neil
    et al.
    Leijon, Mikael
    Jobs, Magnus
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Blomberg, Jonas
    Belak, Sandor
    A novel combination of TaqMan RT-PCR and a suspension microarray assay for the detection and species identification of pestiviruses2010Inngår i: Veterinary Microbiology, ISSN 0378-1135, E-ISSN 1873-2542, Vol. 142, nr 1-2, s. 81-86Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The genus pestivirus contains four recognized species: classical swine fever virus, border disease virus, bovine viral diarrhoea virus types 1 and 2. All are economically important and globally distributed but classical swine fever is the most serious, concerning losses and control measures. It affects both domestic pigs and wild boars. Outbreaks of this disease in domestic pigs call for the most serious measures of disease control, including a stamping out policy in Europe. Since all the members of the pestivirus genus can infect swine, differential diagnosis using traditional methods poses some problems. Antibody tests may lack specificity due to cross-reactions, antigen capture ELISAs may have low sensitivity, and virus isolation may take several days or even longer time to complete. PCR-based tests overcome these problems for the most part, but in general lack the multiplexing capability to detect and differentiate all the pestiviruses simultaneously. The assay platform described here addresses all of these issues by combining the advantages of real-time PCR with the multiplexing capability of microarray technology. The platform includes a TaqMan real-time PCR designed for the universal detection of pestiviruses and a microarray assay that can use the amplicons produced in the real-time PCR to identify the specific pestivirus. (C) 2009 Elsevier B.V. All rights reserved.

  • 190.
    Libungan, Berglind
    et al.
    Sahlgrens university hospital.
    Lindqvist, Jonny
    Sahlgrens university hospital.
    Strömsöe, Anneli
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Nordberg, Per
    Karolinska institutet.
    Hollenberg, Jacob
    Karolinska institutet.
    Albertsson, Per
    Sahlgrens university hospital.
    Karlsson, Thomas
    Göteborgs universitet.
    Herlitz, Johan
    Högskolan Väst.
    Out-of-hospital cardiac arrest in the elderly: a large-scale population-based study2015Inngår i: Resuscitation, ISSN 0300-9572, E-ISSN 1873-1570, Vol. 94, s. 28-32Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

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

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

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

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

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

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

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

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

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

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

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

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

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

  • 193. Lind, L
    et al.
    Ingelsson, E
    Sundström, J
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    The impact of obesity and the metabolic syndrome on the risk of cardiovascular morbidity and mortality in middle-aged men2009Inngår i: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 119, nr 10, s. E302-E302Artikkel i tidsskrift (Fagfellevurdert)
  • 194. Lind, L
    et al.
    Siegbahn, A
    Ingelsson, E
    Sundström, J
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    A detailed cardiovascular characterization of metabolically healthy obesity2009Inngår i: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 119, nr 10, s. E302-E302Artikkel i tidsskrift (Fagfellevurdert)
  • 195. Lind, L
    et al.
    Siegbahn, A
    Ingelsson, E
    Sundström, J
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    A detailed cardiovascular characterization of obesity without the metabolic syndrome2011Inngår i: Arteriosclerosis, Thrombosis and Vascular Biology, ISSN 1079-5642, E-ISSN 1524-4636, Vol. 31, nr 8, s. e27-e34Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

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

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

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

  • 196. Lind, Lars
    et al.
    Carlsson, Axel C
    Siegbahn, Agneta
    Sundström, Johan
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Uppsala universitet.
    Impact of physical activity on cardiovascular status in obesity2017Inngår i: European Journal of Clinical Investigation, ISSN 0014-2972, E-ISSN 1365-2362, Vol. 47, nr 2, s. 167-175Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

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

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

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

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

  • 197. Lind, Lars
    et al.
    Elmståhl, Sölve
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Uppsala universitet.
    Change in body weight from age 20 years is a powerful determinant of the metabolic syndrome2017Inngår i: Metabolic Syndrome and Related Disorders, ISSN 1540-4196, E-ISSN 1557-8518, Vol. 15, nr 3, s. 112-117Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

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

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

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

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

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

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

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

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

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

  • 199. Lind, Lars
    et al.
    Siegbahn, Agneta
    Lindahl, Bertil
    Stenemo, Markus
    Sundström, Johan
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Discovery of new risk markers for ischemic stroke using a novel targeted proteomics chip2015Inngår i: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 46, nr 12, s. 3340-3347Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

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

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

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

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

  • 200. Lind, Lars
    et al.
    Sundström, Johan
    Larsson, Anders
    Lampa, Erik
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Karolinska Institutet.
    Ingelsson, Erik
    Longitudinal effects of aging on plasma proteins levels in older adults: associations with kidney function and hemoglobin levels2019Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 14, nr 2, artikkel-id e0212060Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

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

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

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

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

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