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1.	Zillikens, M Carola, et al. (författare) Erratum: Large meta-analysis of genome-wide association studies identifies five loci for lean body mass. 2017 Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8:1 Tidskriftsartikel (refereegranskat)abstract A correction to this article has been published and is linked from the HTML version of this article.
2.	Teumer, A., et al. (författare) Genomewide meta-analysis identifies loci associated with IGF-I and IGFBP-3 levels with impact on age-related traits 2016 Ingår i: Aging Cell. - : Wiley. - 1474-9718 .- 1474-9726. ; 15:5, s. 811-824 Tidskriftsartikel (refereegranskat)abstract The growth hormone/insulin-like growth factor (IGF) axis can be manipulated in animal models to promote longevity, and IGF-related proteins including IGF-I and IGF-binding protein-3 (IGFBP-3) have also been implicated in risk of human diseases including cardiovascular diseases, diabetes, and cancer. Through genomewide association study of up to 30884 adults of European ancestry from 21 studies, we confirmed and extended the list of previously identified loci associated with circulating IGF-I and IGFBP-3 concentrations (IGF1, IGFBP3, GCKR, TNS3, GHSR, FOXO3, ASXL2, NUBP2/IGFALS, SORCS2, and CELSR2). Significant sex interactions, which were characterized by different genotype–phenotype associations between men and women, were found only for associations of IGFBP-3 concentrations with SNPs at the loci IGFBP3 and SORCS2. Analyses of SNPs, gene expression, and protein levels suggested that interplay between IGFBP3 and genes within the NUBP2 locus (IGFALS and HAGH) may affect circulating IGF-I and IGFBP-3 concentrations. The IGF-I-decreasing allele of SNP rs934073, which is an eQTL of ASXL2, was associated with lower adiposity and higher likelihood of survival beyond 90years. The known longevity-associated variant rs2153960 (FOXO3) was observed to be a genomewide significant SNP for IGF-I concentrations. Bioinformatics analysis suggested enrichment of putative regulatory elements among these IGF-I- and IGFBP-3-associated loci, particularly of rs646776 at CELSR2. In conclusion, this study identified several loci associated with circulating IGF-I and IGFBP-3 concentrations and provides clues to the potential role of the IGF axis in mediating effects of known (FOXO3) and novel (ASXL2) longevity-associated loci. © 2016 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.
3.	Kilpeläinen, Tuomas O, et al. (författare) Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels 2016 Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7 Tidskriftsartikel (refereegranskat)abstract Leptin is an adipocyte-secreted hormone, the circulating levels of which correlate closely with overall adiposity. Although rare mutations in the leptin (LEP) gene are well known to cause leptin deficiency and severe obesity, no common loci regulating circulating leptin levels have been uncovered. Therefore, we performed a genome-wide association study (GWAS) of circulating leptin levels from 32,161 individuals and followed up loci reaching P<10(-6) in 19,979 additional individuals. We identify five loci robustly associated (P<5 × 10(-8)) with leptin levels in/near LEP, SLC32A1, GCKR, CCNL1 and FTO. Although the association of the FTO obesity locus with leptin levels is abolished by adjustment for BMI, associations of the four other loci are independent of adiposity. The GCKR locus was found associated with multiple metabolic traits in previous GWAS and the CCNL1 locus with birth weight. Knockdown experiments in mouse adipose tissue explants show convincing evidence for adipogenin, a regulator of adipocyte differentiation, as the novel causal gene in the SLC32A1 locus influencing leptin levels. Our findings provide novel insights into the regulation of leptin production by adipose tissue and open new avenues for examining the influence of variation in leptin levels on adiposity and metabolic health.
4.	Wallensten, Anders, et al. (författare) Surveillance of influenza A virus in migratory waterfowl in northern Europe 2007 Ingår i: Emerging Infectious Diseases. - 1080-6040 .- 1080-6059. - 1080-6040 ; 13:3, s. 404-411 Tidskriftsartikel (refereegranskat)abstract We conducted large-scale, systematic sampling of influenza type A virus in migratory waterfowl (mostly mallards [Anas platyrhynchos]) at Ottenby Bird Observatory, southeast Sweden. As with previous studies, we found a higher prevalence in fall than spring, and among juveniles compared with adults. However, in contrast to other studies, we found that prevalence in spring was sometimes high (mean 4.0%, highest 9.5%). This finding raises the possibility that ducks are capable of perpetuating influenza A virus of different subtypes and subtype combinations throughout the year and from 1 year to the next. Isolation of the H5 and H7 subtypes was common, which suggests risk for transmission to sensitive domestic animals such as poultry. We argue that wild bird screening can function as a sentinel system, and we give an example of how it could have been used to forecast a remote and deadly outbreak of influenza A in poultry.
5.	Frazier-Wood, Alexis C., et al. (författare) Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses 2016 Ingår i: Nature Genetics. - : Nature Research (part of Springer Nature). - 1061-4036 .- 1546-1718. ; 48, s. 624- Tidskriftsartikel (refereegranskat)abstract Very few genetic variants have been associated with depression and neuroticism, likely because of limitations on sample size in previous studies. Subjective well-being, a phenotype that is genetically correlated with both of these traits, has not yet been studied with genome-wide data. We conducted genome-wide association studies of three phenotypes: subjective well-being (n = 298,420), depressive symptoms (n = 161,460), and neuroticism (n = 170,911). We identify 3 variants associated with subjective well-being, 2 variants associated with depressive symptoms, and 11 variants associated with neuroticism, including 2 inversion polymorphisms. The two loci associated with depressive symptoms replicate in an independent depression sample. Joint analyses that exploit the high genetic correlations between the phenotypes (vertical bar(p) over cap vertical bar approximate to 0.8) strengthen the overall credibility of the findings and allow us to identify additional variants. Across our phenotypes, loci regulating expression in central nervous system and adrenal or pancreas tissues are strongly enriched for association.
6.	Smith, Jennifer A, et al. (författare) Genome-wide association study identifies 74 loci associated with educational attainment 2016 Ingår i: Nature (London). - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 533:7604, s. 539-542 Tidskriftsartikel (refereegranskat)abstract Educational attainment is strongly influenced by social and other environmental factors, but genetic factors are estimated to account for at least 20% of the variation across individuals. Here we report the results of a genome-wide association study (GWAS) for educational attainment that extends our earlier discovery sample of 101,069 individuals to 293,723 individuals, and a replication study in an independent sample of 111,349 individuals from the UK Biobank. We identify 74 genome-wide significant loci associated with the number of years of schooling completed. Single-nucleotide polymorphisms associated with educational attainment are disproportionately found in genomic regions regulating gene expression in the fetal brain. Candidate genes are preferentially expressed in neural tissue, especially during the prenatal period, and enriched for biological pathways involved in neural development. Our findings demonstrate that, even for a behavioural phenotype that is mostly environmentally determined, a well-powered GWAS identifies replicable associated genetic variants that suggest biologically relevant pathways. Because educational attainment is measured in large numbers of individuals, it will continue to be useful as a proxy phenotype in efforts to characterize the genetic influences of related phenotypes, including cognition and neuropsychiatric diseases.
7.	Gongora, M., et al. (författare) Characteristics of Patients in SPCG-15-A Randomized Trial Comparing Radical Prostatectomy with Primary Radiotherapy plus Androgen Deprivation Therapy in Men with Locally Advanced Prostate Cancer 2022 Ingår i: European Urology Open Science. - : Elsevier BV. - 2666-1691 .- 2666-1683. ; 41, s. 63-73 Tidskriftsartikel (refereegranskat)abstract Background: There is no high-grade evidence for surgery as primary treatment for locally advanced prostate cancer. The SPCG-15 study is the first randomized trial comparing surgical treatment with radiotherapy. Objective: To describe the baseline characteristics of the first 600 randomized men in the SPCG-15 study. The study will compare mortality and functional outcomes. Design, setting, and participants: This study is a Scandinavian prospective, open, multicenter phase III randomized clinical trial aiming to randomize 1200 men. Intervention: Radical prostatectomy with or without consecutive radiotherapy (experimental) and radiotherapy with neoadjuvant androgen deprivation therapy (standard of care). Outcome measurements and statistical analysis: Cause-specific survival, metastasis-free survival, overall survival, and patient-reported bowel function, sexual health, and lower urinary tract symptoms were measured. Results and limitations: The distribution of characteristics was similar in the two study arms. The median age was 67 yr (range 45-75 yr). Among the operated men, 36% had pT3a stage of disease and 39% had pT3b stage. International Society of Urological Pathology grades 2, 3, 4, and 5 were prevalent in 21%, 35%, 7%, and 27%, respectively. Half of the men (51%) in the surgery arm had no positive lymph nodes. The main limitation is the pragmatic design comparing the best available practice at each study site leading to heterogeneity of treatment regimens within the study arms. Conclusions: We have proved that randomization between surgery and radiotherapy for locally advanced prostate cancer is feasible. The characteristics of the study population demonstrate a high prevalence of advanced disease, well-balanced comparison groups, and a demography mirroring the Scandinavian population of men with prostate cancer at large. Patient summary: This study, which has recruited >600 men, compares radiotherapy with surgery for prostate cancer, and an analysis at the time of randomization indicates that the study will be informative and generalizable to most men with locally advanced but not metastasized prostate cancer. (C) 2022 The Author(s). Published by Elsevier B.V. on behalf of European Association of Urology.
8.	Prakash, A, et al. (författare) Deliverable D6.3 : Trials and experimentation (cycle 3) 2022 Rapport (refereegranskat)abstract This deliverable presents the third and final cycle of trials and experimentation activities executed over 5GENESIS facilities. The document is the continuation of deliverables D6.1 and D6.2, in the sense that it captures tests carried out over the evolved infrastructures hosting 5GENESIS facilities following the methodology defined in the previous editions of this deliverable. The tests reported in this document focus on i) the final 5G infrastructure deployments that includes radio and core elements mostly in Stand-Alone (SA) deployment configurations based on commercial and open implementations, and ii) the various use cases/applications, some of them also involving field trials. Most of the tests described herein, especially the generic/lab ones are performed using the Open5GENESIS experimentation suite.
9.	Sarwar, Nadeem, et al. (författare) Interleukin-6 receptor pathways in coronary heart disease : a collaborative meta-analysis of 82 studies 2012 Ingår i: The Lancet. - New York, NY, USA : Elsevier. - 0140-6736 .- 1474-547X. ; 379:9822, s. 1205-1213 Tidskriftsartikel (refereegranskat)abstract Background: Persistent inflammation has been proposed to contribute to various stages in the pathogenesis of cardiovascular disease. Interleukin-6 receptor (IL6R) signalling propagates downstream inflammation cascades. To assess whether this pathway is causally relevant to coronary heart disease, we studied a functional genetic variant known to affect IL6R signalling. Methods: In a collaborative meta-analysis, we studied Asp358Ala (rs2228145) in IL6R in relation to a panel of conventional risk factors and inflammation biomarkers in 125 222 participants. We also compared the frequency of Asp358Ala in 51 441 patients with coronary heart disease and in 136 226 controls. To gain insight into possible mechanisms, we assessed Asp358Ala in relation to localised gene expression and to postlipopolysaccharide stimulation of interleukin 6. Findings: The minor allele frequency of Asp358Ala was 39%. Asp358Ala was not associated with lipid concentrations, blood pressure, adiposity, dysglycaemia, or smoking (p value for association per minor allele >= 0.04 for each). By contrast, for every copy of 358Ala inherited, mean concentration of IL6R increased by 34.3% (95% CI 30.4-38.2) and of interleukin 6 by 14.6% (10.7-18.4), and mean concentration of C-reactive protein was reduced by 7.5% (5.9-9.1) and of fibrinogen by 1.0% (0.7-1.3). For every copy of 358Ala inherited, risk of coronary heart disease was reduced by 3.4% (1.8-5.0). Asp358Ala was not related to IL6R mRNA levels or interleukin-6 production in monocytes. Interpretation: Large-scale human genetic and biomarker data are consistent with a causal association between IL6R-related pathways and coronary heart disease.
10.	Gunnarsson, Rebeqa, et al. (författare) Large but not small copy-number alterations correlate to high-risk genomic aberrations and survival in chronic lymphocytic leukemia: A high-resolution genomic screening in newly diagnosed patients 2009 Ingår i: Haematologica-The Hematology Journal. - 0390-6078. ; 94, s. 0354-0354 Konferensbidrag (refereegranskat)
11.	Herlitz, Johan, et al. (författare) Utvärdering av mediakampanj Hjärta-Smärta 90 000 : Fördröjningstiderna vid akut hjärtinfarkt kan förkortas 1991 Ingår i: Läkartidningen. - : Läkartidningen Förlag AB. - 0023-7205 .- 1652-7518. ; 88:37, s. 2973-2977 Tidskriftsartikel (populärvet., debatt m.m.)
12.	Vimaleswaran, Karani S, et al. (författare) Association of vitamin D status with arterial blood pressure and hypertension risk: a mendelian randomisation study. 2014 Ingår i: The lancet. Diabetes & endocrinology. - 2213-8595 .- 2213-8587. ; 2:9, s. 719-29 Tidskriftsartikel (refereegranskat)abstract Background Low plasma 25-hydroxyvitamin D (25[OH]D) concentration is associated with high arterial blood pressure and hypertension risk, but whether this association is causal is unknown. We used a mendelian randomisation approach to test whether 25(OH)D concentration is causally associated with blood pressure and hypertension risk. Methods In this mendelian randomisation study, we generated an allele score (25[OH]D synthesis score) based on variants of genes that affect 25(OH)D synthesis or substrate availability (CYP2R1 and DHCR7), which we used as a proxy for 25(OH)D concentration. We meta-analysed data for up to 108173 individuals from 35 studies in the D-CarDia collaboration to investigate associations between the allele score and blood pressure measurements. We complemented these analyses with previously published summary statistics from the International Consortium on Blood Pressure (ICBP), the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, and the Global Blood Pressure Genetics (Global BPGen) consortium. Findings In phenotypic analyses (up to n=49363), increased 25(OH)D concentration was associated with decreased systolic blood pressure (β per 10% increase, −0·12 mm Hg, 95% CI −0·20 to −0·04; p=0·003) and reduced odds of hypertension (odds ratio [OR] 0·98, 95% CI 0·97–0·99; p=0·0003), but not with decreased diastolic blood pressure (β per 10% increase, −0·02 mm Hg, −0·08 to 0·03; p=0·37). In meta-analyses in which we combined data from D-CarDia and the ICBP (n=146581, after exclusion of overlapping studies), each 25(OH)D-increasing allele of the synthesis score was associated with a change of −0·10 mm Hg in systolic blood pressure (−0·21 to −0·0001; p=0·0498) and a change of −0·08 mm Hg in diastolic blood pressure (−0·15 to −0·02; p=0·01). When D-CarDia and consortia data for hypertension were meta-analysed together (n=142255), the synthesis score was associated with a reduced odds of hypertension (OR per allele, 0·98, 0·96–0·99; p=0·001). In instrumental variable analysis, each 10% increase in genetically instrumented 25(OH)D concentration was associated with a change of −0·29 mm Hg in diastolic blood pressure (−0·52 to −0·07; p=0·01), a change of −0·37 mm Hg in systolic blood pressure (−0·73 to 0·003; p=0·052), and an 8·1% decreased odds of hypertension (OR 0·92, 0·87–0·97; p=0·002). Interpretation Increased plasma concentrations of 25(OH)D might reduce the risk of hypertension. This finding warrants further investigation in an independent, similarly powered study.
13.	Blohm, M, et al. (författare) Reaction to a media campaign focusing on delay in acute myocardial infarction 1991 Ingår i: Heart & Lung. - : Elsevier. - 0147-9563 .- 1527-3288. ; 20:6, s. 661-666 Tidskriftsartikel (refereegranskat)abstract A media campaign conducted to reduce delay time and to increase the use of ambulance transport in acute myocardial infarction was performed in an urban area with about half a million inhabitants during 1 year. The main message was that chest pain lasting more than 15 minutes might indicate acute myocardial infarction; dial 90,000 immediately for ambulance transport to the hospital. The target population was the general public. After 6 and 12 months 400 and 610 randomly chosen persons, respectively, were contacted by telephone to evaluate the reaction of the general public to the campaign. Of these, 60% and 71%, respectively, had heard of the campaign, and all parts of the message were spontaneously remembered by 15% and 19%, respectively. The reaction to the campaign was generally positive. Among all patients admitted to the coronary care unit of one of the two city hospitals, 65% were aware of the campaign and 31% of them were of the opinion that they came to the hospital faster because of the campaign. In conclusion, a media campaign aimed at reducing patient delay time in acute myocardial infarction was shown to reach a majority of people in the community and patients with ischemic heart disease. The reaction was positive and about one fifth of interviewed people spontaneously remembered the total message.
14.	Boonen, Annelies, et al. (författare) EULAR Points to Consider (PtC) for designing, analysing and reporting of studies with work participation as an outcome domain in patients with inflammatory arthritis 2021 Ingår i: Annals of the Rheumatic Diseases. - : BMJ Publishing Group Ltd. - 0003-4967 .- 1468-2060. ; 80:9, s. 1116-1123 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Clinical studies with work participation (WP) as an outcome domain pose particular methodological challenges that hamper interpretation, comparison between studies and meta-analyses.OBJECTIVES: To develop Points to Consider (PtC) for design, analysis and reporting of studies of patients with inflammatory arthritis that include WP as a primary or secondary outcome domain.METHODS: The EULAR Standardised Operating Procedures were followed. A multidisciplinary taskforce with 22 experts including patients with rheumatic diseases, from 10 EULAR countries and Canada, identified methodologic areas of concern. Two systematic literature reviews (SLR) appraised the methodology across these areas. In parallel, two surveys among professional societies and experts outside the taskforce sought for additional methodological areas or existing conducting/reporting recommendations. The taskforce formulated the PtC after presentation of the SLRs and survey results, and discussion. Consensus was obtained through informal voting, with levels of agreement obtained anonymously.RESULTS: Two overarching principles and nine PtC were formulated. The taskforce recommends to align the work-related study objective to the design, duration, and outcome domains/measurement instruments of the study (PtC: 1-3); to identify contextual factors upfront and account for them in analyses (PtC: 4); to account for interdependence of different work outcome domains and for changes in work status over time (PtC: 5-7); to present results as means as well as proportions of patients reaching predefined meaningful categories (PtC: 8) and to explicitly report volumes of productivity loss when costs are an outcome (PtC:9).CONCLUSION: Adherence to these EULAR PtC will improve the methodological quality of studies evaluating WP.
15.	Henriksson, C., et al. (författare) Knowledge and attitudes toward seeking medical care for AMI-symptoms 2009 Ingår i: International Journal of Cardiology. - 1874-1754. ; 147:2, s. 224-227 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Time is crucial when an acute myocardial infarction (AMI) occurs, but patients often wait before seeking medical care. AIM: To investigate and compare patients' and relatives' knowledge of AMI, attitudes toward seeking medical care, and intended behaviour if AMI-symptoms occur. METHODS: The present study was a descriptive, multicentre study. Participants were AMI-patients
16.	Herlitz, Johan, et al. (författare) Effect of media campaign on delay times and ambulance use in suspected acut myocardial infarction 1989 Ingår i: American Journal of Cardiology. - : Excerpta Medica, Inc.. - 0002-9149 .- 1879-1913. ; 64:1, s. 90-93 Tidskriftsartikel (refereegranskat)abstract The early phase in suspected acute myocardial infarction (AMI) is particularly critical. More than 50% of deaths from coronary artery disease occur outside the hospital mainly due to ventricular fibrillation.1 Recent experiences strongly indicate that early intervention with thrombolysis2–4 and β blockers5,6 can limit myocardial damage and thereby improve prognosis. Delay times in suspected AMI have remained stable over the years. Therefore, a media campaign was started in the urban area of Göteborg, Sweden, with the intention to shorten delay times and to increase ambulance use in patients with suspected AMI.
17.	Herlitz, Johan, et al. (författare) Effects of a media campaign to reduce delay times for acute myocardial infarction on the burden of chest pain patients in the emergency department 1991 Ingår i: Cardiology. - : S. Karger AG. - 0008-6312 .- 1421-9751. ; 79:2, s. 127-134 Tidskriftsartikel (refereegranskat)abstract We evaluated the effect of a media campaign aimed at reducing delay times in suspected acute myocardial infarction (AMI) on the volume of chest pain patients seen in the emergency department. During the 1st week of the campaign, the mean number of chest pain patients increased from 10.5 per day prior to the start to 25.4. However, the number declined rapidly in subsequent months. The greatest increase was observed in patients with chest pain in whom AMI was not suspected on examination. During the campaign, 4,805 patients with chest pain appeared in the emergency department as compared with 4,407 patients during the same time period prior to its start, an increase of 9%. The number of patients with confirmed AMI increased from 595 to 629 (6%).
18.	Herlitz, Johan, et al. (författare) Kampanj : Hjärta - Smärta 90.000. Ett försök att förkorta fördröjningstiden vid misstänkt akut hjärtinfarkt 1988 Ingår i: Läkartidningen. - : Läkartidningen Förlag AB. - 0023-7205 .- 1652-7518. ; 85, s. 1999-2001 Tidskriftsartikel (populärvet., debatt m.m.)
19.	Karlsson, Per Erik, 1957, et al. (författare) Risk assessments for forest trees: The performance of the ozone flux versus the AOT concepts 2007 Ingår i: Environmental Pollution. - : Elsevier BV. - 0269-7491. ; 146:3, s. 608-616 Tidskriftsartikel (refereegranskat)abstract Published ozone exposure-response relationships from experimental studies with young trees performed at different sites across Europe were re-analysed in order to test the performance of ozone exposure indices based on AOTX (Accumulated exposure Over a Threshold of X nmol mol(-1)) and AF(st)Y (Accumulated Stomatal Flux above a threshold of Y nmol m(-2) s(-1)). AF(st)1.6 was superior, as compared to AOT40, for explaining biomass reductions, when ozone sensitive species with differing leaf morphology were included in the analysis, while this was not the case for less sensitive species. A re-analysis of data with young black cherry trees, subject to different irrigation regimes, indicated that leaf visible injuries were more strongly related to the estimated stomatal ozone uptake, as compared to the ozone concentration in the air. Experimental data with different clones of silver birch indicated that leaf thickness was also an important factor influencing the development of ozone induced leaf visible injury. (c) 2006 Elsevier Ltd. All rights reserved.
20.	Lehtiö, Janne, et al. (författare) Proteogenomics of non-small cell lung cancer reveals molecular subtypes associated with specific therapeutic targets and immune-evasion mechanisms 2021 Ingår i: Nature Cancer. - : Springer Science and Business Media LLC. - 2662-1347. ; 2:11, s. 1224-1242 Tidskriftsartikel (refereegranskat)abstract Despite major advancements in lung cancer treatment, long-term survival is still rare and a deeper understanding of molecular phenotypes would allow the identification of specific cancer dependencies and immune-evasion mechanisms. Here we performed in-depth mass-spectrometry-based proteogenomic analysis of 141 tumors representing all major histologies of non-small cell lung cancer (NSCLC). We identified six distinct proteome subtypes with striking differences in immune cell composition and subtype-specific expression of immune checkpoints. Unexpectedly, high neoantigen burden was linked to global hypomethylation and complex neoantigens mapped to genomic regions, such as endogenous retroviral elements and introns, in immune-cold subtypes. Further, we linked immune evasion with LAG-3 via STK11 mutation-dependent HNF1A activation and FGL1 expression. Finally, we develop a data-independent acquisition mass-spectrometry-based NSCLC subtype classification method, validate it in an independent cohort of 208 NSCLC cases and demonstrate its clinical utility by analyzing an additional cohort of 84 late-stage NSCLC biopsy samples.
21.	Risenfors, M, et al. (författare) Effects on chest pain of early thrombolytic treatment in suspected acute myocardial infarction : results from the TEAHAT Study 1991 Ingår i: Journal of Internal Medicine. - : Wiley-Blackwell Publishing Ltd.. - 0954-6820 .- 1365-2796. ; 734:suppl 1, s. 27-34 Tidskriftsartikel (refereegranskat)abstract In a randomized, double-blind study, in which recombinant tissue plasminogen activator (rt-PA) administered at an early stage was compared with placebo in patients with suspected acute myocardial infarction (AMI), the effects on pain were studied in 312 patients. Inclusion criteria were as follows: (a) chest pain of duration less than 2 h and 45 min; and (b) age less than 75 years. Chest pain was estimated subjectively by the patients, using a 10-point numerical rating scale, at hourly intervals for the first 24 h, and by the requirement for narcotic analgesics. Compared with placebo, rt-PA treatment resulted in a 43% reduction in mean total pain score (P less than 0.0001), a 26% reduction in pain duration (P less than 0.01), and a 33% reduction in morphine requirement (P = 0.01). Fifty-seven per cent of all patients developed a confirmed AMI. In these subjects rt-PA reduced the pain score by 46% (P less than 0.001). Among patients without confirmed AMI, a 37% reduction in pain score was observed (P = 0.05). The effect on pain was most marked in patients with ST-elevation on the initial ECG. We conclude that early treatment with rt-PA in suspected AMI reduces chest pain considerably. The effect is most marked in patients with ST-elevation on the initial ECG.
22.	Uhlén, Mathias, et al. (författare) The human secretome 2019 Ingår i: Science Signaling. - : American Association for the Advancement of Science (AAAS). - 1945-0877 .- 1937-9145. ; 12:609 Tidskriftsartikel (refereegranskat)abstract The proteins secreted by human cells (collectively referred to as the secretome) are important not only for the basic understanding of human biology but also for the identification of potential targets for future diagnostics and therapies. Here, we present a comprehensive analysis of proteins predicted to be secreted in human cells, which provides information about their final localization in the human body, including the proteins actively secreted to peripheral blood. The analysis suggests that a large number of the proteins of the secretome are not secreted out of the cell, but instead are retained intracellularly, whereas another large group of proteins were identified that are predicted to be retained locally at the tissue of expression and not secreted into the blood. Proteins detected in the human blood by mass spectrometry-based proteomics and antibody-based immuno-assays are also presented with estimates of their concentrations in the blood. The results are presented in an updated version 19 of the Human Protein Atlas in which each gene encoding a secretome protein is annotated to provide an open-access knowledge resource of the human secretome, including body-wide expression data, spatial localization data down to the single-cell and subcellular levels, and data about the presence of proteins that are detectable in the blood.
23.	Augustsson, Anna, et al. (författare) Challenges in assessing the health risks of consuming vegetables in metal-contaminated environments 2018 Ingår i: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 113, s. 269-280 Tidskriftsartikel (refereegranskat)abstract A great deal of research has been devoted to the characterization of metal exposure due to the consumption of vegetables from urban or industrialized areas. It may seem comforting that concentrations in crops, as well as estimated exposure levels, are often found to be below permissible limits. However, we show that even a moderate increase in metal accumulation in crops may result in a significant increase in exposure. We also highlight the importance of assessing exposure levels in relation to a regional baseline. We have analyzed metal (Pb, Cd, As) concentrations in nearly 700 samples from 23 different vegetables, fruits, berries and mushrooms, collected near 21 highly contaminated industrial sites and from reference sites. Metal concentrations generally complied with permissible levels in commercial food and only Pb showed overall higher concentrations around the contaminated sites. Nevertheless, probabilistic exposure assessments revealed that the exposure to all three metals was significantly higher in the population residing around the contaminated sites, for both low-, medianand high consumers. The exposure was about twice as high for Pb and Cd, and four to six times as high for As. Since vegetable consumption alone did not result in exposure above tolerable intakes, it would have been easy to conclude that there is no risk associated with consuming vegetables grown near the contaminated sites. However, when the increase in exposure is quantified, its potential significance is harder to dismiss - especially when considering that exposure via other routes may be elevated in a similar way.
24.	Berglin Blohm, M, et al. (författare) Factors associated with prehospital and in-hospital delay time in acute myocardial infarction : a 6-year experience 1998 Ingår i: Journal of Internal Medicine. - : Wiley-Blackwell Publishing Ltd.. - 0954-6820 .- 1365-2796. ; 243:3, s. 243-250 Tidskriftsartikel (refereegranskat)abstract OBJECTIVES: To explore factors associated with delay time prior to hospital admission and in hospital amongst acute myocardial infarction (AMI) patients with particular emphasis on the delay time to the administration of thrombolytic therapy. METHODS: During a 6-year period we prospectively computerized pre-hospital and in-hospital time intervals for AMI patients admitted to the coronary care unit (CCU) direct from the emergency department (ED) or via paramedics, at Sahlgrenska Hospital, Göteborg, Sweden. RESULTS: Pre-hospital delay: independent predictors of a prolonged delay were increased age (P = 0.0007), female sex (P = 0.02) and a history of hypertension (P = 0.03). For AMI patients who received thrombolytic treatment and the only independent predictor of a prolonged delay was increased age (P = 0.005). In-hospital delay: for all AMI patients independent predictors of a prolonged delay were prolonged pre-hospital delay (P < 0.0001), increased age (P = 0.03) and a history of angina (P = 0.002), hypertension (P = 0.01) and diabetes (P = 0.01). For thrombolytic treated AMI patients independent predictors of a prolonged delay were prolonged pre-hospital delay (P < 0.0001), female sex (P = 0.02) and a history of diabetes (P = 0.02). CONCLUSION: Risk factors for both pre-hospital and hospital delay time could in AMI be defined although slightly different. Two factors appeared for both, i.e. increasing age and a history of hypertension.
25.	Björck, Hanna M., et al. (författare) Characterization of Shear-Sensitive Genes in the NormalRat Aorta Identifies Hand2 as a Major Flow-ResponsiveTranscription Factor 2012 Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:12 Tidskriftsartikel (refereegranskat)abstract Objective: Shear forces play a key role in the maintenance of vessel wall integrity. Current understanding regarding shear-dependent gene expression is mainly based on in vitro or in vivo observations with experimentally deranged shear, hence reflecting acute molecular events in relation to flow. Our objective was to determine wall shear stress (WSS) in the rat aorta and study flow-dependent vessel wall biology under physiological conditions.Methods and Results: Animal-specific aortic WSS magnitude and vector direction were estimated using computational fluid dynamic simulation based on aortic geometry and flow information acquired by MRI. Two distinct flow pattern regions were identified in the normal rat aorta; the distal part of the inner curvature being exposed to low WSS and a non-uniform vector direction, and a region along the outer curvature being subjected to markedly higher levels of WSS and a uniform vector direction. Microarray analysis revealed a strong differential expression between the flow regions, particularly associated with transcriptional regulation. In particular, several genes related to Ca2+-signalling, inflammation, proliferation and oxidative stress were among the most highly differentially expressed.Conclusions: Microarray analysis validated the CFD-defined WSS regions in the rat aorta, and several novel flow-dependent genes were identified. The importance of these genes in relation to atherosusceptibility needs further investigation.
26.	Björkman, Lena, 1965, et al. (författare) Serum amyloid A mediates human neutrophil production of reactive oxygen species through a receptor independent of formyl peptide receptor like-1 2008 Ingår i: Journal of Leukocyte Biology. - : Oxford University Press (OUP). - 0741-5400 .- 1938-3673. ; 83:2, s. 245-53 Tidskriftsartikel (refereegranskat)abstract Serum amyloid A (SAA) is one of the acute-phase reactants, a group of plasma proteins that increases immensely in concentration during microbial infections and inflammatory conditions, and a close relationship between SAA levels and disease activity in rheumatoid arthritis (RA) has been observed. RA is an inflammatory disease, where neutrophils play important roles, and SAA is thought to participate in the inflammatory reaction by being a neutrophil chemoattractant and inducer of proinflammatory cytokines. The biological effects of SAA are reportedly mediated mainly through formyl peptide receptor like-1 (FPRL1), a G protein-coupled receptor (GPCR) belonging to the formyl peptide receptor family. Here, we confirmed the affinity of SAA for FPRL1 by showing that stably transfected HL-60 cells expressing FPRL1 were activated by SAA and that the response was inhibited by the use of the FPRL1-specific antagonist WRWWWW (WRW4). We also show that SAA activates the neutrophil NADPH-oxidase and that a reserve pool of receptors is present in storage organelles mobilized by priming agents such as TNF-alpha and LPS from Gram-negative bacteria. The induced activity was inhibited by pertussis toxin, indicating the involvement of a GPCR. However, based on FPRL1-specific desensitization and use of FPRL1 antagonist WRW4, we found the SAA-mediated effects in neutrophils to be independent of FPRL1. Based on these findings, we conclude that SAA signaling in neutrophils is mediated through a GPCR, distinct from FPRL1. Future identification and characterization of the SAA receptor could lead to development of novel, therapeutic targets for treatment of RA.
27.	Blohm, M, et al. (författare) Mediakampanj om råd vid bröstsmärtor har stor genomslagskraft i befolkningen 1989 Ingår i: Läkartidningen. - : Läkartidningen Förlag AB. - 0023-7205 .- 1652-7518. ; 86:32-33, s. 2695-2696 Tidskriftsartikel (refereegranskat)
28.	Bräutigam, M, et al. (författare) Primär PTCA eller trombolys vid akut hjärtinfarkt? 2001 Ingår i: Läkartidningen. - : Läkartidningen Förlag AB. - 0023-7205 .- 1652-7518. ; 98, s. 3392-3395 Tidskriftsartikel (refereegranskat)
29.	Buggert, Marcus, et al. (författare) Limited immune surveillance in lymphoid tissue by cytolytic CD4+ T cells during health and HIV disease 2018 Ingår i: PLoS Pathogens. - : Public Library of Science (PLoS). - 1553-7374. ; 14:4 Tidskriftsartikel (refereegranskat)abstract CD4+ T cells subsets have a wide range of important helper and regulatory functions in the immune system. Several studies have specifically suggested that circulating effector CD4+ T cells may play a direct role in control of HIV replication through cytolytic activity or autocrine β-chemokine production. However, it remains unclear whether effector CD4+ T cells expressing cytolytic molecules and β-chemokines are present within lymph nodes (LNs), a major site of HIV replication. Here, we report that expression of β-chemokines and cytolytic molecules are enriched within a CD4+ T cell population with high levels of the T-box transcription factors T-bet and eomesodermin (Eomes). This effector population is predominately found in peripheral blood and is limited in LNs regardless of HIV infection or treatment status. As a result, CD4+ T cells generally lack effector functions in LNs, including cytolytic capacity and IFNγ and β-chemokine expression, even in HIV elite controllers and during acute/early HIV infection. While we do find the presence of degranulating CD4+ T cells in LNs, these cells do not bear functional or transcriptional effector T cell properties and are inherently poor to form stable immunological synapses compared to their peripheral blood counterparts. We demonstrate that CD4+ T cell cytolytic function, phenotype, and programming in the peripheral blood is dissociated from those characteristics found in lymphoid tissues. Together, these data challenge our current models based on blood and suggest spatially and temporally dissociated mechanisms of viral control in lymphoid tissues.
30.	Buker, P., et al. (författare) DO3SE modelling of soil moisture to determine ozone flux to forest trees 2012 Ingår i: Atmospheric Chemistry and Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 12:12, s. 5537-5562 Tidskriftsartikel (refereegranskat)abstract The DO3SE (Deposition of O-3 for Stomatal Exchange) model is an established tool for estimating ozone (O-3) deposition, stomatal flux and impacts to a variety of vegetation types across Europe. It has been embedded within the EMEP (European Monitoring and Evaluation Programme) photochemical model to provide a policy tool capable of relating the flux-based risk of vegetation damage to O-3 precursor emission scenarios for use in policy formulation. A key limitation of regional flux-based risk assessments has been the assumption that soil water deficits are not limiting O-3 flux due to the unavailability of evaluated methods for modelling soil water deficits and their influence on stomatal conductance (g(sto)), and subsequent O-3 flux. This paper describes the development and evaluation of a method to estimate soil moisture status and its influence on g(sto) for a variety of forest tree species. This DO3SE soil moisture module uses the Penman-Monteith energy balance method to drive water cycling through the soil-plant-atmosphere system and empirical data describing g(sto) relationships with pre-dawn leaf water status to estimate the biological control of transpiration. We trial four different methods to estimate this biological control of the transpiration stream, which vary from simple methods that relate soil water content or potential directly to g(sto), to more complex methods that incorporate hydraulic resistance and plant capacitance that control water flow through the plant system. These methods are evaluated against field data describing a variety of soil water variables, g(sto) and transpiration data for Norway spruce (Picea abies), Scots pine (Pinus sylvestris), birch (Betula pendula), aspen (Populus tremuloides), beech (Fagus sylvatica) and holm oak (Quercus ilex) collected from ten sites across Europe and North America. Modelled estimates of these variables show consistency with observed data when applying the simple empirical methods, with the timing and magnitude of soil drying events being captured well across all sites and reductions in transpiration with the onset of drought being predicted with reasonable accuracy. The more complex methods, which incorporate hydraulic resistance and plant capacitance, perform less well, with predicted drying cycles consistently underestimating the rate and magnitude of water loss from the soil. A sensitivity analysis showed that model performance was strongly dependent upon the local parameterisation of key model drivers such as the maximum g(sto), soil texture, root depth and leaf area index. The results suggest that the simple modelling methods that relate g(sto) directly to soil water content and potential provide adequate estimates of soil moisture and influence on g(sto) such that they are suitable to be used to assess the potential risk posed by O-3 to forest trees across Europe.
31.	Dellborg, M, et al. (författare) Changes in the use of medication after acute myocardial infarction : Possible impact on post-myocardial infarction mortality and long-term outcome 2001 Ingår i: Coronary Artery Disease. - : Lippincott Williams & Wilkins. - 0954-6928 .- 1473-5830. ; 12:1, s. 61-67 Tidskriftsartikel (refereegranskat)abstract Objective: To describe the change in the use of medication after acute myocardial infarction (AMI) and discuss its possible impact on risk and risk indicators for death. Patients: All patients discharged alive after hospitalization for AMI at Sahlgrenska Hospital (covering half the community of Goteborg, i.e. 250 000 of 500 000 inhabitants) during 1986-1987 (period I) and at Sahlgrenska Hospital and Ostra Hospital (covering the whole community of Goteborg, 500 000 inhabitants) during 1990-1991 (period II). Methods: Overall mortality was retrospectively evaluated during 5 years of follow-up. Results: In all, 740 patients were included in the study during period I and 1448 during period II. The 5-year mortalities were 44.1% for period I patients and 39.3% for period II patients (P = 0.036). The relative risk of death for period II patients was 0.78 [95% confidence interval (CI) 0.67-0.89, P = 0.0005] after adjustment for differences at baseline. There was a significant interaction with a history of congestive heart failure; improvement in duration of survival was found only for patients without such a history. During period I, only 3% of patients were administered fibrinolytic agents, compared with 33% of patients during period II (P < 0.0001). During period I, aspirin was prescribed for 13% of patients discharged from hospital compared with 79% during period II. Other changes in treatment on going from period I to period II included increases in prescription of [beta]-blockers and angiotensin converting enzyme inhibitors. After adjustment for various risk indicators for death, relative risk of death for those administered fibrinolytic agents was 0.60 (95% CI 0.18-2.02) for patients in the period-I cohort and 0.68% (95% CI 0.51-0.91) for those in the period-II cohort. Adjusted relative risk of death for those prescribed aspirin upon discharge from hospital was 0.81 (95% CI 0.52-1.25) for period-I patients and 0.71 (95% CI 0.56-0.91) for period-II patients. The adjusted relative risk of death for those administered [beta]-blockers was 0.72 (95% CI 0.55-0.96) for period-I patients and 0.70 (95% CI 0.55-0.90) for period-II patients. Conclusion: Increased use of fibrinolytic agents and aspirin for AMI as well as a moderate increase in use of [beta]-blockers and angiotensin converting enzyme inhibitors was associated with a parallel reduction in age-adjusted mortality during the 5 years after discharge from hospital. However, this improvement was seen only for patients without histories of congestive heart failure.
32.	Erriah, M., et al. (författare) Galectin-3 enhances monocyte-derived macrophage efferocytosis of apoptotic granulocytes in asthma 2019 Ingår i: Respiratory Research. - : Springer Science and Business Media LLC. - 1465-993X. ; 20 Tidskriftsartikel (refereegranskat)abstract BackgroundGalectin-3 is a 32kDa protein secreted by macrophages involved in processes such as cell activation, chemotaxis and phagocytosis. Galectin-3 has previously been shown to improve the ability of airway macrophages to ingest apoptotic cells (efferocytosis) in chronic obstructive pulmonary disease (COPD) and may be of interest in non-eosinophilic asthma (NEA) which is also characterised by impaired efferocytosis. It was hypothesised that the addition of exogenous galectin-3 to monocyte-derived macrophages (MDMs) derived from donors with NEA would enhance their ability to engulf apoptotic granulocytes.MethodsEligible non-smoking adults with asthma (n=19), including 7 with NEA and healthy controls (n=10) underwent a clinical assessment, venepuncture and sputum induction. MDMs were co-cultured with apoptotic granulocytes isolated from healthy donors with or without exogenous recombinant galectin-3 (50g/mL) and efferocytosis was assessed by flow cytometry. Galectin-3 expression and localisation in MDMs was visualised by immunofluorescence staining and fluorescence microscopy. Galectin-3, interleukin (IL)-6 and CXCL8 secretion were measured in cell culture supernatants by ELISA and cytometric bead array.ResultsBaseline efferocytosis (mean (standard deviation)) was lower in participants with asthma (33.2 (+/- 17.7)%) compared with healthy controls (45.3 (+/- 15.9)%; p=0.081). Efferocytosis did not differ between the participants with eosinophilic asthma (EA) (31.4 (+/- 19.2)%) and NEA (28.7 (+/- 21.5)%; p=0.748). Addition of galectin-3 significantly improved efferocytosis in asthma, particularly in NEA (37.8 (+/- 18.1)%) compared with baseline (30.4 (+/- 19.7)%; p=0.012). Efferocytosis was not associated with any of the clinical outcomes but was negatively correlated with sputum macrophage numbers (Spearman r=-0.671; p=0.017). Galectin-3 was diffusely distributed in most MDMs but formed punctate structures in 5% of MDMs. MDM galectin-3 secretion was lower in asthma (9.99 (2.67, 15.48) ng/mL) compared with the healthy controls (20.72 (11.28, 27.89) ng/mL; p=0.044) while IL-6 and CXCL8 levels were similar.Conclusions p id=Par4 Galectin-3 modulates macrophage function in asthma, indicating a potential role for galectin-3 to reverse impaired efferocytosis in NEA.
33.	Hartford, M, et al. (författare) Components of delay time in suspected acute myocardinal infarction with particular emphasis on patient delay 1990 Ingår i: Journal of Internal Medicine. - : Wiley-Blackwell Publishing Ltd.. - 0954-6820 .- 1365-2796. ; 228:5, s. 519-523 Tidskriftsartikel (refereegranskat)abstract Two hundred and thirty-four patients admitted to a coronary care unit (CCU) were interviewed a few days after arrival in hospital to determine reasons for patient delay and the various components of total delay time from onset of symptoms to arrival in CCU. Of the three major components of delay, decision time (time from onset of symptoms to decision to go to hospital), and hospital procedure time (time from arrival in hospital to arrival in the CCU), were of the same magnitude, 1 h 15 min and 1 h 30 min (median), whereas the median time for preparation and transportation to hospital was somewhat shorter, being 45 min. Decision time appeared to be similar in patients with confirmed and non-confirmed acute myocardial infarction (AMI) and was not associated with intensity of pain or infarct size. Half of the patients hesitated to go to hospital, which resulted in a prolonged decision delay (3 h). It is concluded that patient indecision to seek medical help is the most important reason for delay in hospital arrival in patients with suspected AMI.
34.	Herlitz, Johan, et al. (författare) Delay time in suspected acute myocardial infarction and the importance of its modification 1989 Ingår i: Clinical Cardiology. - : John Wiley & Sons, Inc.. - 0160-9289 .- 1932-8737. ; 12:7, s. 370-374 Tidskriftsartikel (refereegranskat)abstract This paper summarizes the present knowledge of delay time in suspected acute myocardial infarction. More than 50% of deaths in acute myocardial infarction occur outside of the hospital setting. Recent experiences indicate that early and even late mortality can be dramatically reduced by intervention in the early phase. This points up the importance of bringing patients with suspected acute myocardial infarction to the hospital as early in the course of MI as possible. The predominating cause of delay is the time it takes for the patient to decide to go to hospital regardless of a previous history of cardiovascular disease. Patients arriving in hospital in later stages of MI are at a very high risk of mortality. Therefore one of the most important problems to be resolved is how to reduce delay time in suspected acute myocardial infarction. Such efforts have been surprisingly few. Limited experiences indicate that public education can reduce delay time dramatically.
35.	Herlitz, Johan, et al. (författare) Determinants of an impaired quality of life five years after coronary artery bypass surgery 1999 Ingår i: Heart. - : B M J Group. - 1355-6037 .- 1468-201X. ; 81:4, s. 342-346 Tidskriftsartikel (refereegranskat)abstract OBJECTIVE—To identify determinants of an inferior quality of life (QoL) five years after coronary artery bypass grafting (CABG). SETTING—University hospital. PARTICIPANTS—Patients from western Sweden who underwent CABG between 1988 and 1991. MAIN OUTCOME MEASURES—Questionnaires for evaluating QoL before CABG and five years after operation. Three different instruments were used: the Nottingham health profile (NHP), the psychological general wellbeing index (PGWI), and the physical activity score (PAS). RESULTS—2121 patients underwent CABG, of whom 310 died during five years' follow up. Information on QoL after five years was available in 1431 survivors (79%). There were three independent predictors for an inferior QoL with all three instruments: female sex, a history of diabetes mellitus, and a history of chronic obstructive pulmonary disease. Multivariate analysis showed that a poor preoperative QoL was a strong independent predictor for an impaired QoL five years after CABG. An impaired QoL was also predicted by previous disease. CONCLUSIONS—Female sex, an impaired QoL before surgery, and other diseases such as diabetes mellitus are independent predictors for an impaired QoL after CABG in survivors five years after operation.
36.	Herlitz, Johan, et al. (författare) Diagnostic accuracy of physicians for identifying patients with acute myocardial infarction without an electrocardiogram. Experiences from the TEAHAT trial 1995 Ingår i: Cardiology. - : S. Karger AG. - 0008-6312 .- 1421-9751. ; 86:1, s. 25-27 Tidskriftsartikel (refereegranskat)abstract AIM: To determine the diagnostic accuracy of physicians for identifying patients with acute myocardial infarction (AMI) without an electrocardiogram (ECG). PATIENTS: All patients in Göteborg with suspected AMI below 75 years of age who called for an ambulance or came directly to one of the two city hospitals with a delay time of less than 2 h 45 min from the start of symptoms. METHODS: As part of the TEAHAT study (comparing rt-PA and placebo in AMI), we asked physicians to judge on a 1-5 scale (1 = no suspicion; 5 = convinced) how strong their suspicion of AMI was prior to interpreting the ECG. RESULTS: Among patients evaluated outside hospital with 4 or 5 on the scale, i.e. either a strong suspicion of AMI or the physician felt convinced about the diagnosis, 45% had ST elevation and 48% developed AMI during the first 3 days in hospital. The corresponding values for patients evaluated in hospital were 67 and 70%, respectively. CONCLUSION: We found that physicians could not accurately distinguish patients with AMI from those without based on clinical criteria without the help of an ECG.
37.	Herlitz, Johan, et al. (författare) Impact of a history of diabetes mellitus on quality of life after coronary bypass grafting 1998 Ingår i: European Journal of Cardio-Thoracic Surgery. - : Elsevier BV. - 1010-7940 .- 1873-734X. ; 12:6, s. 853-861 Tidskriftsartikel (refereegranskat)abstract AIM: To describe the improvement in various aspects of quality of life (QoL) after coronary artery bypass grafting (CABG), in relation to a previous history of diabetes mellitus. PATIENTS: All patients from western Sweden who underwent CABG between 1988 and 1991 without simultaneous valve surgery. METHODS: Patients were approached with three questionnaires: The Physical Activity Score, the Nottingham Health Profile and the Psychological General Well-being Index prior to surgery and 3 months, 1 and 2 years thereafter. RESULTS: All three questionnaires already showed a significant improvement in QoL after 3 months, remaining at a similar level 1 and 2 years after the operation. In terms of Physical Activity Score improvement was of similar magnitude in diabetic and non-diabetic patients. In terms of the Psychological General Well-Being Index significant and similar improvements were found in diabetic and non-diabetic patients at each evaluation. In terms of the Nottingham Health Profile there was a significant improvement both in diabetic and non-diabetic patients 3 months, 1 and 2 years after the operation. However, improvement was more marked in diabetic than in non-diabetic patients at each evaluation. CONCLUSION: For 3 months, 1 and 2 years after CABG various aspects of QoL as estimated with three different instruments, improved significantly both in diabetic and in non-diabetic patients compared with the situation prior to the operation. However, the three instruments differed somewhat. Thus, whereas in the Physical Activity Score, diabetic patients tended to improve less markedly than non-diabetic patients, the opposite was found in the Nottingham Health Profile.
38.	Herlitz, Johan, et al. (författare) Impact of a history of hypertension on symptoms and Quality of Life prior to and at five years after coronary artery bypass grafting 2000 Ingår i: Blood Pressure. - : Informa Healthcare. - 0803-7051 .- 1651-1999. ; 9:1, s. 52-63 Tidskriftsartikel (refereegranskat)abstract AIM: To describe symptoms and other aspects of health-related quality of life (QoL) prior to and 5 years after coronary artery bypass grafting (CABG) in relation to a history of hypertension. METHODS: Patients who underwent CABG in western Sweden were approached prior to surgery and 5 years after the operation. Health-related QoL was estimated with the Physical Activity Score, the Nottingham Health Profile and the Psychological General Well-Being Index. RESULTS: In patients with a history of hypertension (n = 740) the 5-year mortality was 16.9% versus 12.4% among patients with no history (n = 1257; p = 0.004). Of 1717 patients available for the survey, 876 (51%) responded both prior to and 5 years after CABG. Of these, 36% had a history of hypertension. Compared with the situation prior to surgery there was an improvement in both hypertensive and non-hypertensive patients in terms of physical activity, symptoms of dyspnea and chest pain and other estimates of health-related QoL. However, physical activity and dyspnea improved less in hypertensive than in non-hypertensive patients. CONCLUSION: Five years after CABG, a marked and significant improvement in terms of symptoms and other aspects of health-related QoL was observed among both hypertensive and non-hypertensive patients. However, improvement in physical activity was less marked in patients with a history of hypertension. Overall, a history of hypertension seemed to have a minor impact on improved well-being 5 years after coronary surgery. However, because of the limited response rate the results may not be applicable in a non-selected CABG population.
39.	Herlitz, Johan, et al. (författare) Improvement and factors associated with improvement in quality of life during 10 years after coronary artery bypass grafting 2003 Ingår i: Coronary Artery Disease. - : Lippincott Williams & Wilkins. - 0954-6928 .- 1473-5830. ; 14:7, s. 509-517 Tidskriftsartikel (refereegranskat)abstract AIM: To describe (1) the improvement in various aspects of quality of life (QoL) and (2) predictors of improvement, during 10 years after coronary artery bypass grafting (CABG). PATIENTS AND METHODS: All patients who underwent CABG in western Sweden between June 1988 and June 1991 without simultaneous valve surgery and with no previous CABG were approached with an inquiry prior to and 5 and 10 years after the operation. QoL was measured with three different instruments: (1) Nottingham health profile (NHP), (2) psychological general well-being index (PGWBI) and (3) physical activity score (PAS). RESULTS: There was a significant improvement in QoL with all three instruments from before to 10 years after the operation. The mean improvements +/-SD were for NHP, - 4.2+/-17.0 (P<0.0001), for PGWBI, +9.7+/-17.6 (P<0.0001) and for PAS, -0.96+/-1.23 (P<0.0001). However, there was also a deterioration with all three instruments between 5 and 10 years after surgery. The mean deteriorations +/-SD were for NHP, +4.4+/-12.8 (P<0.0001), for PGWBI, -4.6+/-14.8 (P<0.0001) and for PAS, +0.44+/-0.94 (P<0.0001). Independent predictors for an improvement in QoL with at least one of the instruments were low preoperative QoL, a younger age, being a man, high functional class (New York Heart Association), no hypertension, proximal left anterior descending coronary artery stenosis, short extracorporeal circulation time, use of internal mammary artery and a short postoperative time in the intensive care unit. CONCLUSION: There is a higher estimated QoL 10 years after CABG than before, despite the fact that the patients are 10 years older. However, there is also a deterioration in QoL between 5 and 10 years after surgery. Predictors of improvement during the 10 years included age, sex, previous history, localization of stenosis, type of graft and preoperative and postoperative factors.
40.	Herlitz, Johan, et al. (författare) Limitation of physical activity, dyspnea and chest pain prior to and during two years after coronary artery bypass grafting in relation to a history of hypertension 1998 Ingår i: Blood Pressure. - : Informa Healthcare. - 0803-7051 .- 1651-1999. ; 6:6, s. 349-356 Tidskriftsartikel (refereegranskat)abstract AIM: To describe the limitation of physical activity, the cause of limitation of physical activity and symptoms of dyspnea and chest pain before and 2 years after coronary artery bypass grafting (CABG) in relation to a history of hypertension. METHODS: All patients from western Sweden who underwent CABG between 1988 and 1991 were approached with a questionnaire--prior to, 3 months and 2 years after CABG--evaluating the issues raised above. RESULTS: Of 2121 patients, 37% had a history of hypertension. By 3 months after CABG, physical activity tolerance had improved markedly and in a similar way for both hypertensive (p<0.001) and non-hypertensive patients (p<0.001); this level was sustained for 2 years. Absence of dyspnea increased markedly and similarly among both hypertensive and non-hypertensive patients (p < 0.001) after CABG. The presence of chest pain decreased markedly and similarly among hypertensive (p<0.001) and non-hypertensive patients (p<0.001), both 3 months and 2 years after compared to prior to the operation. CONCLUSION: There was a marked improvement in terms of physical activity and cardiovascular symptoms 3 months and 2 years after CABG as compared with the situation prior to the operation. A previous history of hypertension did not seem to affect these results.
41.	Herlitz, Johan, et al. (författare) Mortality and morbidity during a period of 2 years after coronary artery bypass surgery in patients with and without a history of hypertension 1996 Ingår i: Journal of Hypertension. - : Lippincott Williams & Wilkins, Ltd.. - 0263-6352 .- 1473-5598. ; 14:3, s. 309-314 Tidskriftsartikel (refereegranskat)abstract OBJECTIVE: To describe mortality and morbidity during a period of 2 years after coronary artery bypass grafting (CABG) in relation to a history of hypertension. PATIENTS: All patients in western Sweden in whom CABG was undertaken between June 1988 and June 1991 and in whom simultaneous valve surgery was not performed were included in the study. DESIGN: A prospective 2-year follow-up study. RESULTS: Patients with a history of hypertension (n = 777) differed from patients without such a history (n = 1348) in that the proportion of women was higher, they were older and more frequently had a history of congestive heart failure, diabetes mellitus, renal dysfunction, cerebro-vascular disease, intermittent claudication and obesity, and the number of smokers and patients with previous CABG was lower. They were also more likely to develop post-operative cerebrovascular complications and signs of myocardia damage. Patients with hypertension tended to have increased mortality during the first 30 days after CABG and the late mortality (between day 30 and 2 years) was significantly higher than in non-hypertensive participants. Whereas the development of myocardial infarction was similar in both groups, the hypertensive study participants more frequently developed stroke during 2 years of follow-up. In a multivariate analysis including age, sex, history of different cardiovascular diseases, smoking, ejection fraction, and the occurrence of three-vessel disease, hypertension did not emerge as an independent predictor of death in the early or late phase or during a total of 2 years of follow-up. CONCLUSION: Among CABG patients, those with a history of hypertension have a different pattern of risk factors. They have a higher mean age, include a higher proportion of women and have a higher prevalence of congestive heart failure, diabetes mellitus, renal dysfunction, cerebro-vascular disease, intermittent claudication, and obesity. They also have an increased frequency of immediate post-operative complications and an increased 2-year mortality, even if a history of hypertension was not an independent predictor of death during 2 years of follow-up.
42.	Herlitz, Johan, et al. (författare) Mortality, mode of death and risk indicators for death during 5 years after coronary artery bypass grafting among patients with and without a history of diabetes mellitus 2000 Ingår i: Coronary Artery Disease. - : Lippincott Williams & Wilkins. - 0954-6928 .- 1473-5830. ; 11:4, s. 339-346 Tidskriftsartikel (refereegranskat)abstract OBJECTIVE: To describe mortality, mode of death, risk indicators for death and symptoms of angina pectoris among survivors during 5 years after coronary artery bypass grafting (CABG) among patients with and without a history of diabetes mellitus. METHODS: All patients in western Sweden who underwent CABG without concomitant valve surgery and who had no previous CABG between June 1988 and June 1991 were entered prospectively in this study. After 5 years, information on deaths that had occurred was obtained for the analysis. RESULTS: In all, 1998 patients were included in the analysis; 242 (12%) had a history of diabetes. Among the non-diabetic patients, 5-year mortality was 12.5%; the corresponding relative risk for diabetic patients was 2.1 (95% confidence interval 1.6 to 2.9). A history of diabetes was an independent risk indicator of death; there was no significant interaction between any other risk indicator and diabetes. Independent risk indicators for death among diabetic patients were: current smoking, renal dysfunction and left ventricular ejection fraction < 0.40. Compared with non-diabetic patients, those with diabetes more frequently died in hospital, died a cardiac death, or had death associated with the development of acute myocardial infarction and with symptoms of congestive heart failure. Among survivors, diabetic patients tended to have more angina pectoris 5 years after CABG than did those without diabetes. CONCLUSION: During a period of 5 years after CABG, diabetic patients had a mortality twice that of non-diabetic patients. The increased risk included death in hospital, cardiac death and death associated with development of acute myocardial infarction and with symptoms of congestive heart failure.
43.	Herlitz, Johan, et al. (författare) Mortality, risk indicators for death and mode of death in younger and elderly patients during 5 years coronary artery bypass graft. 2000 Ingår i: Clinical Cardiology. - : John Wiley & Sons, Inc.. - 0160-9289 .- 1932-8737. ; 23:6, s. 421-426 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: The number of elderly patients who may be candidates for coronary artery bypass graft (CABG) for severe coronary artery disease has increased. Cardiac surgery in the elderly is a high-risk procedure because many of these patients have concomitant systemic disease and other disabilities. HYPOTHESIS: The study was undertaken to evaluate mortality, risk indicators for death, and mode of death in younger and elderly patients during 5 years after CABG. METHODS: The study included all patients in western Sweden who underwent CABG without concomitant valve surgery and without previously performed CABG between June 1988 and June 1991. In all, 2,000 patients, of whom 953 (48%) were > or = 65 years, were divided into two age groups (< 65 years and > or = 65 years). RESULTS: Compared with the younger patients, the elderly had a relative risk of death of 2.3 (95% confidence interval 1.8-3.0). The increased risk of death in the elderly was significantly more marked in men, in patients with more severe angina pectoris, and in patients without a history of cerebrovascular diseases. The mode and place of death appeared similar regardless of age; neither was there marked difference in symptoms of angina pectoris among survivors 5 years after CABG. CONCLUSION: Compared with patients < 65 years, the elderly have more than twice as high a risk of death during the subsequent 5 years, and this risk is higher in men, in patients with severe symptoms of angina pectoris, and in those with no history of cerebrovascular disease.
44.	Herlitz, Johan, et al. (författare) Mortality, risk indicators for death, mode of death and symptoms of angina pectoris during 5 years after coronary artery bypass grafting in men and women 2000 Ingår i: Journal of Internal Medicine. - : Wiley-Blackwell Publishing Ltd.. - 0954-6820 .- 1365-2796. ; 247:4, s. 500-506 Tidskriftsartikel (refereegranskat)abstract AIM: To describe mortality, risk indicators of death, mode of death and symptoms of angina pectoris during 5 years after coronary artery bypass grafting in women and men. SAMPLE: All patients in western Sweden who underwent coronary artery bypass grafting without concomitant valve surgery and without previously performed coronary artery bypass grafting between June 1988 and June 1991. RESULTS: In all, 2000 patients participated in the evaluation, 381 (19%) of whom were women. Compared to men, who had a 5-year mortality of 13.3%, women had a relative risk of death of 1.4 (95% CI 1.0-1.8; P = 0.03). Renal dysfunction interacted significantly (P = 0.048) with gender, in that the differences were more marked in patients without renal dysfunction. When adjusting for differences at baseline, the relative risk of death amongst women was 1.0 (95% CL 0.7-1.3). Compared to men, women had an increased risk of in-hospital death and death associated with stroke. However, amongst the patients who died, the place and mode of death appeared to be similar in women and men. Amongst survivors after 5 years, women had more symptoms of angina pectoris than men. CONCLUSION: During 5 years after coronary artery bypass grafting, women had an increased mortality compared to men; renal dysfunction seemed to interact with female gender regarding mortality. Women had a higher risk of in-hospital death and death associated with stroke. However, the adjusted relative risk of death during 5 years was equal in women and men. Amongst survivors, women suffered more from angina pectoris than men.
45.	Herlitz, Johan, et al. (författare) Mortality, risk indicators mode and place of death and symptoms of angina pectoris in the five years after coronary artery bypass grafting in patients with and without a history of hypertension 1999 Ingår i: Blood Pressure. - : Informa Healthcare. - 0803-7051 .- 1651-1999. ; 8:4, s. 200-206 Tidskriftsartikel (refereegranskat)abstract AIM: To describe mortality, risk indicators for death, place and mode of death, and symptoms of angina pectoris among survivors in the 5 years after coronary artery bypass grafting (CABG) in patients with and without a history of hypertension. METHODS: All patients in western Sweden who underwent CABG without concomitant valve surgery and without previously performed CABG between June 1988 and June 1991. RESULTS: A total of 1997 patients were included in the analysis, 740 (37%) of whom had a history of hypertension. Patients with no history had a 5-year mortality of 12.4%. The corresponding relative risk for hypertensives was 1.4 (95% CI 1.1-1.8). Risk factors for death appeared similar in patients with and without a history of hypertension. Patients with hypertension had an increased risk of death in hospital and an increased risk of a non-cardiac death. Among survivors after 5 years, patients with a history of hypertension tended to have a higher prevalence of symptoms equivalent to angina pectoris. CONCLUSIONS: Patients with a history of hypertension have an increased risk of death in the 5 years after CABG. Risk factors for death appear similar in patients with and without a history of hypertension. Patients with hypertension have a particularly increased risk of death in hospital and of death judged as non-cardiac.
46.	Herlitz, Johan, et al. (författare) One year mortality after acute myocardial infarction prior to and after the implementation of a widespread use of thrombolysis and aspirin 1997 Ingår i: Cardiology. - : S. Karger AG. - 0008-6312 .- 1421-9751. ; 89:3, s. 216-221 Tidskriftsartikel (refereegranskat)abstract During 1 year of follow-up, we compared the mortality after acute myocardial infarction (AMI) prior to and after the introduction of a more widespread use of thrombolytic agents and aspirin. STUDY PERIOD: Two periods (I = 1986-1987 and II = 1989-1990) were compared. PATIENTS: All patients admitted to the coronary care units at the two city hospitals in the community of Goteborg who fulfilled the criteria for development of AMI participated in the evaluation. RESULTS: The overall 1-year mortality rate was 27% [corrected] during period I and 23% during period II (NS). However, among patients up to 70 years of age, the mortality was reduced from 15 to 11% (p < 0.05), whereas among patients aged over 70 years the mortality remained almost unchanged (34 vs. 35%; NS). CONCLUSION: The introduction of a more widespread use of thrombolytic agents and aspirin has not substantially changed the overall mortality in AMI. However, among younger patients, the mortality appears to have been reduced but not among the elderly.
47.	Herlitz, Johan, et al. (författare) Physical activity, dyspnea and chest pain prior to and after coronary artery bypass grafting in relation to a history of diabetes 1998 Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 21:10, s. 1603-1611 Tidskriftsartikel (refereegranskat)abstract OBJECTIVE: To describe the limitation of physical activity and symptoms of chest pain and dyspnea before and after coronary artery bypass grafting (CABG) in relation to a history of diabetes. RESEARCH DESIGN AND METHODS: All patients in western Sweden in whom CABG was performed between 1988 and 1991 were asked to complete a questionnaire before 3 months and 2 years after the operation. The questionnaire evaluated limitation of physical activity and symptoms of chest pain and dyspnea. RESULTS: In all, 2,121 patients participated in the evaluation, of whom 13% had a history of diabetes. The overall 2-year mortality was 14% among patients with a history of diabetes and 6% among patients without such a history (P < 0.001). The proportion of patients with a limitation of physical activity caused by chest pain decreased from 76% before CABG to 19% 2 years after in diabetic patients (P < 0.001) and from 79 to 17% in nondiabetic patients (P < 0.001). The proportion of diabetic patients without dyspnea increased from 13% before to 31% 2 years after CABG (P < 0.001). The corresponding figures for nondiabetic patients were 12 and 43% (P < 0.001). Symptoms of angina pectoris were reported in 94% of diabetic patients before CABG versus 35% after 2 years (P < 0.001). Corresponding figures for nondiabetic patients were 93 and 29% (P < 0.001). Aggregate data confirmed differences between diabetic and nondiabetic patients, with more symptoms in the diabetic patients, particularly with regard to dyspnea. CONCLUSIONS: Mortality during 2 years of follow up was more than twice as high in diabetic than in nondiabetic patients. Limitation of physical activity, dyspnea, and angina pectoris improved markedly and similarly in diabetic and nondiabetic patients after CABG. Whereas limitation of physical activity and dyspnea was more frequent in diabetic than in nondiabetic patients, the occurrence of angina pectoris was more similar in the two groups.
48.	Herlitz, Johan, et al. (författare) Physical activity, symptoms of chest pain and dyspnea in patients with ischemic heart disease in relation to age before and two years after coronary artery bypass grafting 2001 Ingår i: Journal of Cardiovascular Surgery. - : Edizioni Minerva Medica. - 0021-9509 .- 1827-191X. ; 42:2, s. 165-173 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: To describe limitation of physical activity, cause of limitation of physical activity and symptoms of dyspnea and chest pain in relation to age before and 2 years after coronary artery bypass grafting (CABG). METHODS: All patients from Western Sweden who underwent CABG without concomitant procedures during 3 years in 1989-1991 answered questionnaires before, and 2 years after the operation. Patients were divided into 3 age groups of equal size i.e. 32-59 years, 60-67 years and > or = 68 years. RESULTS: In total, 2121 patients participated in the evaluation. The overall 2 year mortality in the 3 age groups was 3.8%, 6.8% and 12.2% (p<0.001). Limitation of physical activity was significantly associated with age prior to surgery but not thereafter. Improvement in physical activity, following CABG, was significant in all age groups. The proportion of patients being free of dyspnea increased markedly regardless of age. The number of chest pain attacks was associated with age after CABG, i.e. fewer attacks in the elderly, but such an association was not found prior to surgery. Improvement in number of chest pain attacks was more marked in the elderly. CONCLUSIONS: Physical activity improved similarly in all age groups after CABG. Attacks of chest pain, although significantly reduced in all age groups, seemed more effectively reduced in the elderly.
49.	Herlitz, Johan, et al. (författare) Predictors of death during 5 years after coronary artery bypass grafting 1998 Ingår i: International Journal of Cardiology. - : Elsevier Ireland Ltd. - 0167-5273 .- 1874-1754. ; 64:1, s. 15-23 Tidskriftsartikel (refereegranskat)abstract Aim: To describe predictors of death during five years of follow-up after coronary artery bypass grafting (CABG). Methods: All patients who underwent CABG during a period of three years in Western Sweden were included in the analysis and were prospectively followed for five years. Mortality was related to preoperative and peroperative factors as well as findings at physical examination and medication 4–7 days after the operation. Results: In all 2121 patients underwent CABG without simultaneous valve surgery during the study period. The overall five-year mortality was 14.6%. The following appeared as independent predictors of death during five years but >30 days after CABG: Current smoking (relative risk ratio 2.43 [95% Ci 1.64–3.61]) degree of impairment of left ventricular function (1.51 [1.23–1.86]), a history of congestive heart failure (1.91 [1.35–2.70]), age (1.04 [1.02–1.06]) arrhythmia 4–7 days after CABG (1.89 [1.26–2.83]), intermittent claudication (1.73 [1.19–2.52]), a history of diabetes (1.71 [1.16–2.51]), time in respirator (1.43 [1.13–1.81]), a history of cerebrovascular disease (1.72 [1.13–2.64]), treatment with digitalis at day 4–7 (1.48 [1.07–2.05]), enzyme release (1.49 [1.03–2.16]). Conclusion: Among patients who underwent CABG 11 independent predictors for mortality were found including smoking habits at CABG, history of cardiovascular diseases, left ventricular dysfunction, age, post operative complications and medication after CABG.
50.	Herlitz, Johan, et al. (författare) Predictors of hospital readmission two years after coronary artery bypass grafting 1997 Ingår i: Heart. - : BMJ Group. - 1355-6037 .- 1468-201X. ; 77:5, s. 437-442 Tidskriftsartikel (refereegranskat)abstract OBJECTIVE: To determine the clinical factors before, and in association with, coronary artery bypass grafting (CABG) that increase the risk of readmission to hospital in the first two years after surgery. PATIENTS: All patients in western Sweden who had CABG without simultaneous valve surgery between 1 June 1988 and 1 June 1991. METHODS: All patients who were readmitted to hospital were evaluated by postal inquiry and hospital records. RESULTS: A total of 2121 patients were operated on, of whom 2037 were discharged from hospital. Information regarding readmission was missing in four patients, leaving 2033 patients; 44% were readmitted to hospital. The most common reasons for readmission were angina pectoris and congestive heart failure. There were 12 independent significant predictors for readmission: clinical history (a previous history of either congestive heart failure or myocardial infarction, or CABG); acute operation; postoperative complications (time in intensive care unit greater than two days, neurological complications); clinical findings four to seven days after the operation (arrhythmia, systolic murmur equivalent to mitral regurgitation); medication four to seven days after the operation (antidiabetics, diuretics for heart failure, other antiarrhythmics (other than beta blockers, calcium antagonists, and digitalis), and lack of treatment with aspirin). CONCLUSION: 44% of patients were readmitted to hospital two years after CABG. The most common reasons for readmission were angina pectoris and congestive heart failure. Four clinical markers predicted readmission: clinical history; acute operation status; postoperative complications; and clinical findings and medication four to seven days after operation.

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