Aarhus University Hospital

Arhus, Denmark

Aarhus University Hospital

Arhus, Denmark
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News Article | April 18, 2017
Site: www.eurekalert.org

The commonly used antibiotic azithromycin is not linked to an increased risk of ventricular arrhythmia, an often life-threatening rapid, irregular heartbeat, according to a large study published in CMAJ (Canadian Medical Association Journal). Azithromycin is an antibiotic commonly used to treat bacterial infections -- mostly respiratory and urinary tract infections -- in people of all ages. It belongs to a class of drugs known as macrolides, of which at least one other drug, erythromycin, is known to disrupt the heart's normal rhythm, leading to a condition known as ventricular arrhythmia. Several recent studies have reported conflicting results over whether azithromycin is linked to an increased risk of death from ventricular arrhythmia in people taking the antibiotic. To provide clarity among these conflicting findings, a team of European researchers looked at data on nearly 29 million people in health care databases from Italy, the United Kingdom, Germany, the Netherlands and Denmark to determine if there is a link between azithromycin and ventricular arrhythmia. Of the more than 14 million new antibiotic users, 0.1% (12 874) people developed ventricular arrhythmia, of whom 30 were new users of azithromycin. When compared to amoxicillin, another commonly used antibiotic, from the penicillin class of drugs, there was no increased risk of this heart condition in people using azithromycin. However, there was an increased risk of ventricular arrhythmia in people taking azithromycin compared to people not using antibiotics at all. "This finding suggests that the risk of ventricular arrhythmia is more likely to be due to a person's poor health and caused by their infection, rather than to azithromycin itself," says Dr. Gianluca Trifirò, Department of Biomedical and Dental Sciences and Morpho-functional Imaging, University of Messina, Italy. "This finding was confirmed in several sensitivity analyses and replicated in single databases participating in the study." The authors note these findings may not be applied in hospital settings as the health of patients and use of antibiotics is quite different in community settings, from which the data were drawn. "Current azithromycin use was associated with an increased risk of ventricular arrhythmia when compared with nonuse of antibiotics, but not when compared with current amoxicillin use. The decreased risk with an active comparator suggests significant confounding by indication," the authors conclude. The study was conducted by researchers from Erasmus University, Rotterdam, Netherlands; University of Messina, Messina, Italy; Italian College of General Practitioners, Florence, Italy; PHARMO Institute for Drug Outcomes Research, Utrecht, Netherlands; Leibniz Institute for Prevention Research and Epidemiology - BIPS Gmbh, Bremen, Germany; University of Bologna, Italy; Aarhus University Hospital, Aarhus, Denmark; and King's College, London, United Kingdom.


News Article | May 29, 2017
Site: www.prweb.com

Global molecular diagnostics company Omixon, headquartered in Budapest with US offices in Cambridge, MA, announce today that Holotype HLA™ and other Omixon products will be featured in 12 poster presentations produced by Holotype customers at the annual meeting of the European Federation for Immunogenetics (EFI) in Mannheim, Germany. Additionally, Omixon’s Lunch Symposium on Wednesday will focus on Automated HLA Typing by NGS and feature three presentations from current Holotype HLA users from the EMEA region. Among the customer presentations the most common theme is the superiority of NGS compared with legacy methods, in which rare alleles created by rare crossing over events (P118, Thomas Binder et al.) or novel alleles (P119 & P123, Xavier Lafarge et al.) can be easily determined by Holotype HLA and remain a challenge for SBT. Another popular theme is the comparison of various NGS technologies (P115, Amalia Dinou et al. and Petra Neukirchen et al.) in which the strengths of Holotype HLA are showcased against those of other vendors. Additional examples of these themes are captured in a poster presented by Omixon’s Dr. Libor Kolesar (P110), who will focus on the “Super Powers” of NGS compared to legacy technologies and highlight unique capabilities of Holotype HLA. Omixon’s Lunch Symposium on May 31 will have three customer experience stories featuring Dr. Alexandre Walencik from the Etablissement Français du Sang (EFS), Nantes who will present their experience with Holotype HLA. “One year after, does NGS really change the world in a HLA laboratory?” Dr Walencik will their share good experiences, obstacles and their solutions with a focus on technical and organizational ways and means to encourage more labs adopt NGS for HLA such as Holotype HLA. Dr. Reem Ameen from Kuwait University will focus on describing the validation process for introducing Holotype HLA in clinical setting and her project to extend the known HLA haplotypes in several families of Kuwaiti descent. Dr. Ameen identified haplotypes that were not among the 200 most common HLA haplotypes in any of the 5 major US populations and included 199 (17%) unique alleles, 26 rare alleles, 6 very rare alleles and 2 novels. Kuwaiti individuals carry unique HLA haplotypes that are not shared by any of the majority of subjects historically reported to the US National Marrow Donor Program (NMDP) registry - a fascinating population with tremendous potential for ongoing HLA research. Dr. Mette Christiansen from the Aarhus University Hospital, Denmark will share their experiences on Automation of the Holotype HLA on the Beckman Biomek 4000. NGS has ushered in an era of increased capacity for HLA genotyping in terms of pooling more loci and processing larger numbers of samples thus placing ever more importance on repeatability and reproducibility. Handling of multiple samples at multiple loci simultaneously and eventually combining these into a single tube requires tightly controlled procedures, which may be achieved by automation. She will focus on the obstacles encountered and the benefits achieved in the automation process. Marcello Scala, Director of Sales, EMEA at Omixon says, “The explosion in labs adopting Holotype HLA throughout Europe and Middle East has been truly astonishing. Even more impressive is the affection customers have for the technology due to its unrivaled ability to resolve the genotypes of complex samples for the benefit of patients and the transplant community as a whole.” Omixon at EFI 2017 May 30 - June 02 | Omixon will be exhibiting at Booth #18 throughout the conference May 30, 9.30am - 11am | Resolving Laboratory NGS Assay Challenges with HLA Twin May 30, 11.30am-1pm | Resolving Complex Cases of NGS-based HLA Typing with HLA Twin May 31, 1.30pm-2.30pm | High-throughput Automation of Holotype HLA in Clinical Routine Omixon featured in posters P108 | E. Bauer et al. (2017) - Full-length sequencing of a novel MICA allele variant P110 | L. Kolesar et al. (2017) - Superpowers of NGS P111 | J. Diegel et al. (2017) - HLA-E genotyping – the sooner the better P115 | A. Dinou et al. (2017) - Evaluation of a commercially available HLA typing kit for NGS P117 | T. Binder et al. (2017) - Complete human leukocyte antigen gene sequence determination combining long range polymerase chain reaction and next generation sequencing P118 |T. Binder et al. (2017) - Whole gene sequence determination of a rare human leukocyte antigen DRB1 allele by combining long range polymerase chain reaction and next generation sequencing. P119 | X. Lafarge et al. (2017) - Exon phasing permits identification of new alleles by NGS not detectable by Sanger sequence-based typing P121 | P. Neukirchen et al. (2017) - NGS based HLA typing: comparison of four protocols and corresponding software P123 | X. Lafarge et al. (2017) Validation and routine setting of HLA typing by Next Generation Sequencing using the HOLOTYPE HLA (OMIXON) kits : a multicentric experience P127 | A. Hansen et al. (2017) - Implementing ABO genotyping into HLA sequencing workflow P129 | L. Krammes et al. (2017) - What’s new genotyping KIR2DL5? P145 | M. Dorak et al. (2017) - HLA-A, -B, -C typing by next generation sequencing in a sample of Turkish population About Omixon Omixon is a global molecular diagnostics company, headquartered in Budapest, Hungary, with US offices in Cambridge, MA that commercializes disruptive technologies for clinical and research laboratories. Omixon’s flagship product, Holotype HLA™, is the world’s leading NGS-based HLA genotyping product that delivers the most accurate high-resolution HLA genotyping available, and is used in more than 35 hospitals worldwide. Omixon’s research software, HLA Explore™ analyzes data from any sequencing technology and determines HLA genotypes from Whole Exome/Genome Sequencing experiments. Omixon maintains an active grant-funded research program with a product pipeline focused on pre- and post-transplantation, and HLA genotyping applications beyond transplantation.


Acarix CADScor®System - an advanced, easy to use, frontline test to rule out Coronary Artery Disease with high accuracy. On display at British Cardiovascular Society Meeting in Manchester, June 5-7. In preparation for launch, Swedish/Danish Acarix AB's (publ) ("Acarix") CADScor®System will be on display at the British Cardiovascular Society Annual Meeting in Manchester, June 5-7. Delegates will have the opportunity to review first results from a study that was presented at the American College of Cardiology Annual Scientific Meeting held in Washington, March 17-19, 2017 showing that CADScor®System non-invasively rules out Coronary Artery Disease (CAD) with 97% negative predictive value. According to figures from the British Heart Foundation, cardiovascular disease accounts for around 26% of all deaths in the UK, some 116,000 per year with earlier diagnosis being a clear priority for the NHS. The research was led by Principal Investigator Morten Böttcher, MD PhD FESC and by Simon Winther, MD PhD, Department of Cardiology, Aarhus University Hospital, Denmark: "Despite the availability of improved risk stratification algorithms, the incidence of normal investigations such as nuclear or CT imaging remains high. We therefore tested the diagnostic accuracy of the CADScor®System for ruling out CAD to see if it could be used to reduce demand for more advanced diagnostic modalities. We have concluded that, with its ability to rule out CAD with a 97% negative predictive value, this advanced, easy to use, stethoscope like device could indeed be deployed as a frontline test." "We are very pleased with the results of the trial and are now preparing for launching the device. As well as being a major problem in the UK, CAD affects more than 120 million people worldwide but the current diagnostic pathway, which can rapidly escalate to imaging and coronary angiography can be significantly improved. If adopted, the CADScor®System can provide rapid frontline assessment which could translate into an improved triage thus securing that patients in need of further diagnostic tests get them and that patients with symptoms unrelated to CAD do not." The CADScor®System uses ultra-sensitive phonocardiography combined with advanced electronics and algorithms to rule out CAD with 97% negative predictive value. CADScor®System is fast, radiation-free, non-invasive and can be performed in every standard point-of-care environment in less than 10 minutes. In patients with suspected CAD, the current practice includes one or several examinations, i.e.  stress tests, nuclear imaging and invasive coronary angiography. In many cases, these patients are either healthy or end up not needing any treatment. The new CADScor®System is designed to provide a first rapid and non-invasive, investigative step and by ruling out CAD earlier, the diagnostic pathway improves. CADScor®System will be on display at the British Cardiovascular Society Annual Meeting in Manchester, booth number 17. Acarix A/S was established in 2009, and since 2010 investors SEED Capital (DK) and Sunstone Life Science Ventures (DK) have supported it towards market introduction. Acarix has attracted a highly-experienced management team who have held senior positions in international medical device companies - CEO Søren Rysholt Christiansen with ELOS Medtech, GN ReSound and Cook Medical. Acarix's CADScor®System is based on engineering excellence in sound recording and signal processing. It has long been known that both cardiac contraction movement and turbulent flow can generate sound. Contraction related sounds are in lower frequency, whereas turbulent sounds in the streaming blood caused by partial obstruction (stenosis) in the coronary arteries are of higher frequencies. The detection of these murmurs is delicate, since the energy of the murmurs is very weak. Detecting and recording the coronary murmurs requires not only an advanced sensor but also means for proper attachment to the skin above the heart to optimize the recorded signal and to avoid external noise. The Acarix CADScor®System has been designed to be an all-in-one system in the sense that the heart signal will be recorded, processed and displayed as a patient specific score, the CAD-score, on the device screen. The CADScor®System contains the necessary electronics to instruct professionals during use and to guide through the recording periods. The system also contains a docking station for daily qualification of the sensor. Further the system integrates with an adhesive patch for locking the CADScor® sensor to a fixed position above the heart during the recording. The software embedded in The Acarix CADScor®System ensures that adequate recording conditions are controlled at every examination. The CADScor®System is CE Marked (by TÜV in 2015) and planned for commercial launch in Q2 2017. See more at www.acarix.com Press kit: http://www.acarix.com/about-us/press-downloads/.


In patients with ST-segment elevation myocardial infarction (STEMI), delay between contact with the health care system and initiation of reperfusion therapy (system delay) is associated with mortality, but data on the associated risk for congestive heart failure (CHF) among survivors are limited. To evaluate the association between system delay and the risk for readmissions or outpatient contacts due to CHF after primary percutaneous coronary intervention (PPCI) in patients with STEMI. Historical follow-up study using population-based medical registries. Western Denmark. Patients with STEMI who were transported by emergency medical service from 1 January 1999 to 7 February 2010 and treated with PPCI within 12 hours of symptom onset and who had a system delay of 6 hours or less (n = 7952). The median duration of follow-up was 3.1 years. Cumulative incidence of readmissions or outpatient contacts due to CHF was determined by using competing-risk regression analysis, with death as the competing risk. Crude and adjusted cause-specific hazard ratios for readmissions or outpatient contacts due to CHF were determined for system delay and other covariates. System delays of 60 minutes or less (n = 451), 61 to 120 minutes (n = 3457), 121 to 180 minutes (n = 2655), and 181 to 360 minutes (n = 1389) corresponded with long-term risks for readmissions or outpatient contacts due to CHF of 10.1%, 10.6%, 12.3%, and 14.1%, respectively (P < 0.001). In multivariable analysis, system delay was an independent predictor of readmissions or outpatient contacts due to CHF (adjusted hazard ratio per hour increase in delay, 1.10 [95% CI, 1.02 to 1.17]). In any nonrandomized study, there are risks for selection bias and residual confounding. In patients with STEMI, shorter delay to PPCI is associated with lower risk for readmissions or outpatient contacts due to CHF during follow-up.


Sundvall L.,Aarhus University Hospital
Human reproduction (Oxford, England) | Year: 2013

How consistent is the time-lapse annotation of dynamic and static morphologic parameters of embryo development, within and between observers? The assessment of dynamic parameters is characterized by almost perfect agreement within and between observers. The commonly employed method used to assess embryos in IVF treatments is based on static evaluation of morphology in a microscope, but this is limited by substantial intra- and inter-observer variation. Time-lapse imaging has been proposed as a method to refine embryo selection by adding new dynamic predictors of viability to the assessment. Yet, there are no data regarding the consistency of estimates of the time-lapse parameters. Infertile patients were recruited at the Fertility Clinic, Arhus University Hospital from February 2011 to June 2012. All embryos were cultured for 6 days in a time-lapse incubator (EmbryoScope(™)). Automated image recording was performed every 20 min. In total, 158 fertilized embryos from 20 different patients were annotated. Three observers made independent annotations on time-lapse recordings. One observer performed the assessment twice. Twenty-five parameters were annotated and the inter- and intra-observer agreement was assessed by calculating intra-class correlation coefficients (ICCs). Extremely close agreement (ICC 0.99) was found for dynamic parameters including the timing of the following: pronuclei breakdown, completion of blastocyst hatching and the appearance and disappearance of the first nucleus after the first division. Observations of cleavage divisions were strongly correlated (ICC > 0.8), indicating close agreement. Measurements of the static morphologic parameters, i.e. multi-nucleation and evenness of blastomeres at 2-cell stage showed fair-to-moderate agreement (ICC ≤ 0.5). The study was conducted at a single clinic. Only embryos with a good prognosis were included. The influence of training sessions was not measured. Consistency is crucial to the validity of embryo scoring and selection. All of the time-lapse parameters suggested by the literature showed in our study high intra- and inter-observer correlation, thus validating the precision of time-lapse annotations. This provides the basis for further investigation of embryo assessment and selection by time-lapse imaging in prospective trials. Research at the Fertility Clinic was funded by an unrestricted grant from Ferring and MSD. The authors have no competing interests to declare. NCT01139268.


Bek T.,Aarhus University Hospital
Progress in Retinal and Eye Research | Year: 2013

Disturbances in the retinal vascular supply are involved in the pathophysiology of the most frequent diseases causing visual impairment and blindness in the Western World. These diseases are diagnosed by noting how morphological lesions in the retina vary in shape, size, location and dynamics, and subsequently concluding the presence of a specific disease entity. This diagnostic approach can be used to identify the site of a retinal vascular occlusion, to assess whether retinal diseases are primarily due to changes in the larger retinal vessels or the microcirculation, and to differentiate the relative involvement of the choroidal and the retinal vascular systems. However, a number of morphological manifestations of retinal vascular disease cannot presently be related to the underlying pathophysiology. The review concludes that there is a need for developing new methods for assessing vascular structure and function in the ciliary vascular system supplying the choroid and the optic nerve head. Presently, the study of these structures relies on imaging techniques with limited penetration and resolution into the tissue. Secondly, there is a need for studying oscillations in retinal vascular function occurring within days to weeks, and for studying regional manifestations of retinal vascular disease. This may constitute the basis for future research in retinal vascular pathophysiology and for the development of new treatment modalities to reduce blindness secondary to retinal vascular disease. © 2013 Elsevier Ltd.


Norskov-Lauritsen N.,Aarhus University Hospital
Clinical Microbiology Reviews | Year: 2014

The aim of this review is to provide a comprehensive update on the current classification and identification of Haemophilus and Aggregatibacter species with exclusive or predominant host specificity for humans. Haemophilus influenzae and some of the other Haemophilus species are commonly encountered in the clinical microbiology laboratory and demonstrate a wide range of pathogenicity, from life-threatening invasive disease to respiratory infections to a nonpathogenic, commensal lifestyle. New species of Haemophilus have been described (Haemophilus pittmaniae and Haemophilus sputorum), and the new genus Aggregatibacter was created to accommodate some former Haemophilus and Actinobacillus species (Aggregatibacter aphrophilus, Aggregatibacter segnis, and Aggregatibacter actinomycetemcomitans). Aggregatibacter species are now a dominant etiology of infective endocarditis caused by fastidious organisms (HACEK endocarditis), and A. aphrophilus has emerged as an important cause of brain abscesses. Correct identification of Haemophilus and Aggregatibacter species based on phenotypic characterization can be challenging. It has become clear that 15 to 20% of presumptive H. influenzae isolates from the respiratory tracts of healthy individuals do not belong to this species but represent nonhemolytic variants of Haemophilus haemolyticus. Due to the limited pathogenicity of H. haemolyticus, the proportion of misidentified strains may be lower in clinical samples, but even among invasive strains, a misidentification rate of 0.5 to 2% can be found. Several methods have been investigated for differentiation of H. influenzae from its less pathogenic relatives, but a simple method for reliable discrimination is not available. With the implementation of identification by matrix-assisted laser desorption ionization-time of flight mass spectrometry, the more rarely encountered species of Haemophilus and Aggregatibacter will increasingly be identified in clinical microbiology practice. However, identification of some strains will still be problematic, necessitating DNA sequencing of multiple housekeeping gene fragments or full-length 16S rRNA genes. © 2014, American Society for Microbiology. All Rights Reserved.


Donskov F.,Aarhus University Hospital
Seminars in Cancer Biology | Year: 2013

The clinical relevance of the interaction between human cancer and neutrophils has recently begun to emerge. This review will focus on recently published articles regarding immunomonitoring of neutrophils in blood and tumor tissue in clinical trials comprising the main human tumor types, with a strong emphasis on independent prognostic relevance assessed by multivariate analyses.The prognostic role of tumor-infiltrating neutrophils, elevated blood neutrophils and elevated blood neutrophil/lymphocyte ratio has been associated with poor clinical outcome in several human cancers, most notably in renal cell carcinoma, melanoma, colorectal cancer, hepatocellular carcinoma, cholangiocarcinoma, glioblastoma, GIST, gastric, esophageal, lung, ovarian and head and neck cancer. A striking finding is the notion that high baseline neutrophil count in either tumor or blood, or both, was identified as strong, independent risk factor for poor outcome in multivariate analyses, and the negative prognostic impact of neutrophils was not eliminated by increasing the dose of cytokines, chemotherapy, or targeted therapy. For several cancers, patients benefit most from therapy if baseline neutrophil was low. Thus, baseline neutrophils over-ride nadir counts in prognostic significance.In summary, a proportion of patients who do not experience benefit from surgery or medical intervention may be associated with a worst prognosis because they are characterized by baseline tumor-related neutrophilia protecting them from benefit from therapy. Further research to unraveling the cancer biology and new treatment options is encouraged. © 2013 Elsevier Ltd.


Finnerup N.B.,Aarhus University Hospital
Pain | Year: 2013

Individuals with spinal cord injury (SCI) often have chronic pain, which may have a major impact on their quality of life. The purpose of this article is to present an update on the classification of SCI pain, recent advances in the understanding of underlying mechanisms, and current evidence-based treatment of SCI pain. The paper also discusses difficulties in assessing pain after SCI, both in the clinic and in preclinical research. While we continue to increase our understanding of underlying mechanisms, treatment is still unsatisfactory, and there is an unmet need to improve pain relief. We need to improve preclinical assessment of pain-like behavior in central pain models, and improve the clinical assessment of pain and our understanding of the interaction with cognitive, emotional, and social factors. In future studies on mechanisms and treatment, we need to acknowledge the different phenotypes of chronic SCI pain. © 2012 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.


Background: The importance of tumour hypoxia for the outcome of radiotherapy has been under investigation for decades. Numerous clinical trials modifying the hypoxic radioresistance in squamous cell carcinoma of the head and neck (HNSCC) have been conducted, but most have been inconclusive, partly due to a small number of patients in the individual trial. The present meta-analysis was, therefore, performed utilising the results from all clinical trials addressing the specific question of hypoxic modification in HNSCC undergoing curative intended primary radiotherapy alone. Methods: A systematic review of published and unpublished data identified 4805 patients with HNSCC treated in 32 randomized clinical trials, applying, normobaric oxygen or carbogen breathing (5 trials); hyperbaric oxygen (HBO) (9 trials); hypoxic radiosensitizers (17 trials) and HBO and radiosensitizer (1 trial). The trials were analysed with regard to the following endpoints: loco-regional control (32 trials), disease specific survival (30 trials), overall survival (29 trials), distant metastases (12 trials) and complications to radiotherapy (23 trials). Results: Overall hypoxic modification of radiotherapy in head and neck cancer did result in a significant improved therapeutic benefit. This was most dominantly observed when using the direct endpoint of loco-regional control with an odds ratio (OR) of 0.71, 95% cf.l. 0.63-0.80; p < 0.001), but this was almost mirrored in the disease specific survival (OR: 0.73, 95% cf.l. 0.64-0.82; p < 0.001), and to a lesser extent in the overall survival (OR: 0.87, 95% cf.l. 0.77-0.98; p = 0.03). The risk of distant metastases was not significantly influenced although it appears to be less in the tumours treated with hypoxic modification (OR: 0.87, 95% cf.l. 0.69-1.09; p = 0.22), whereas the radiation related late complications were not influenced by the overall use of hypoxic modifications (OR: 1.00, 95% cf.l. 0.82-1.23; p = 0.96). The improvement in loco-regional control was found to be independent of the type of hypoxic modification. The trials have used different fractionation schedules, including large doses per fraction, which may result in relatively more hypoxia and greater benefit. However, analysis of HNSCC trials using conventional fractionation only, showed that the significant effect of hypoxic modification was maintained. Conclusion: The meta-analysis thus demonstrates that there is level 1a evidence in favour of adding hypoxic modification to radiotherapy of squamous cell carcinomas of the head and neck. © 2011 Elsevier Ltd. All rights reserved.

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