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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.

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.

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.

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.

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.

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