Nijmegen, Netherlands
Nijmegen, Netherlands

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Van Der Hoeven J.G.,Radboudumc
Nederlands Tijdschrift voor Geneeskunde | Year: 2016

Power is a charged issue but, when executed with integrity, a potent instrument to improve quality of care. Execution of power has various manifestations, which have an important effect on several aspects of the care process including the doctor-patient relationship, primary responsible physician and the relationship with other team members. Abuse of power is a source of conflicts and may also result in emotional exhaustion and burnout. Various measures may stimulate the appropriate use of power.


Muller A.E.,Radboudumc | Muller A.E.,St Elisabeth Hospital | Punt N.,Medimatics | Moutona J.W.,Erasmus Medical Center
Antimicrobial Agents and Chemotherapy | Year: 2014

The percentage of the dosing interval that the non-protein-bound plasma concentration is above the MIC (%fT>MIC) for cephalosporins has been shown to correlate with microbiological outcomes in preclinical studies. However, clinical data are scarce. Using data from a randomized double-blind phase 3 clinical trial, we explored the relationship of ceftobiprole exposure with microbiological and clinical outcomes in patients with nosocomial pneumonia. The individual ceftobiprole exposure was determined for different pharmacokinetic (PK)/pharmacodynamic (PD) indices using individual pharmacokinetic data and a previously published population model. The MICs used in the analysis were the highest MICs for any bacterium cultured at baseline or the end of treatment (EOT). Outcomes were microbiological cure at EOT and clinical cure at test of cure (TOC). Multiple logistic regression (MLR) and classification and regression tree (CART) analyses were applied to determine the relationships among exposure, patient characteristics, and outcomes. MLR indicated that the%fT>MIC of ceftobiprole was the best predictor for both microbiological eradication and clinical cure. CART analysis showed a breakpoint value of 51.1% (n=159; P=0.0024) for clinical cure, whereas it was 62.2% (n=251; P<0.0001) for microbiological eradication. Other factors also contributed, particularly to clinical outcome. These included the difference between VAP and non-VAP patients, systemic inflammatory response syndrome (SIRS), creatinine clearance, the use of anti-Pseudomonas combination therapy, and Acute Physiology and Chronic Health Evaluation II (APACHE-II) score. There is a strong correlation between microbiological eradication and clinical cure with exposure to ceftobiprole. The%fT>MIC required to result in a favorable clinical outcome is>51% of the dosing interval, which is in line with the values found for microbiological eradication, the comparator ceftazidime, and preclinical models. © 2014, American Society for Microbiology.


Weinreb J.C.,Yale University | Barentsz J.O.,Radboudumc | Choyke P.L.,U.S. National Institutes of Health | Cornud F.,University of Paris Descartes | And 8 more authors.
European Urology | Year: 2016

The Prostate Imaging - Reporting and Data System Version 2 (PI-RADS™ v2) is the product of an international collaboration of the American College of Radiology (ACR), European Society of Uroradiology (ESUR), and AdMetech Foundation. It is designed to promote global standardization and diminish variation in the acquisition, interpretation, and reporting of prostate multiparametric magnetic resonance imaging (mpMRI) examination, and it is based on the best available evidence and expert consensus opinion. It establishes minimum acceptable technical parameters for prostate mpMRI, simplifies and standardizes terminology and content of reports, and provides assessment categories that summarize levels of suspicion or risk of clinically significant prostate cancer that can be used to assist selection of patients for biopsies and management. It is intended to be used in routine clinical practice and also to facilitate data collection and outcome monitoring for research. © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.


Hayrapetyan A.,Radboudumc | Jansen J.A.,Radboudumc | Van Den Beucken J.J.J.P.,Radboudumc
Tissue Engineering - Part B: Reviews | Year: 2015

Bone regeneration is a well organized but complex physiological process, in which different cell types and their activated signaling pathways are involved. In bone regeneration and remodeling processes, mesenchymal stem cells (MSCs) have a crucial role, and their differentiation during these processes is regulated by specific signaling molecules (growth factors/cytokines and hormones) and their activated intracellular networks. Especially the utilization of the molecular machinery seems crucial to consider prior to developing bone implants, bone-substitute materials, and cell-based constructs for bone regeneration. The aim of this review is to provide an overview of the signaling mechanisms involved in bone regeneration and remodeling and the osteogenic potential of MSCs to become a key cellular resource for such regeneration and remodeling processes. Additionally, an overview of possibilities to beneficially exploit cell signaling processes to optimize bone regeneration is provided. © Copyright 2015, Mary Ann Liebert, Inc.


Seyedmousavi S.,Erasmus University Rotterdam | Verweij P.E.,Radboudumc | Mouton J.W.,Erasmus University Rotterdam
Expert Review of Anti-Infective Therapy | Year: 2015

The prodrug isavuconazonium sulfate (BAL8557) is an extended-spectrum water-soluble triazole, developed for the treatment of severe invasive and life-threatening fungal diseases. Its active moiety, BAL4815, is a potent inhibitor of ergosterol biosynthesis, resulting in the disruption of fungal membrane structure and function. The active compound shows broad-spectrum of activity and potency against all major opportunistic fungi, such as Aspergillus spp., Candida spp., Cryptococcus spp., Mucorales, Black yeasts and their filamentous relatives and the true pathogenic fungi, including Histoplasma capsulatum and Blastomyces dermatitidis. It is currently in Phase III clinical development for treatment of aspergillosis, candidiasis and mucormycosis, as well as other rare fungi infections. We reviewed the pharmacokinetic and pharmacodynamic characteristics of isavuconazole, and its microbiological and clinical investigation progress in advanced stages of development. © Informa UK, Ltd.


Sobbi S.C.,Radboudumc | Van den Boogaard M.,Radboudumc
Critical Care | Year: 2014

The pathophysiological mechanism of the serious and frequently occurring disorder delirium is poorly understood. Inflammation and sepsis are known risk factors for ICU delirium and therefore these patients are highly susceptible to delirium. Several studies have been performed to determine which cytokines are most associated with delirium but the results are inconclusive. Also, new biomarkers associated with brain dysfunction and cognitive impairment are still recognized and need to be studied to determine their relation with delirium. In this commentary we address some limitations concerning an interesting new study that warrants directions for future studies. © 2014 Cheheili Sobbi and van den Boogaard; licensee BioMed Central Ltd.


Lepor H.,New York University | Llukani E.,New York University | Sperling D.,Sperling Prostate Cancer Center | Futterer J.J.,Radboudumc
European Urology | Year: 2015

From April 2013 to July 2014, 25 consecutive men participated in a longitudinal outcomes study following in-bore magnetic resonance imaging (MRI)-guided focal laser ablation (FLA) of prostate cancer (PCA). Eligibility criteria were clinical stage T1c and T2a disease; prostate-specific antigen (PSA) <10 ng/ml; Gleason score <8; and cancer-suspicious regions (CSRs) on multiparametric MRI harboring PCA. CSRs harboring PCA were ablated using a Visualase cooled laser applicator system. Tissue temperature was monitored throughout the ablation cycle by proton resonance frequency shift magnetic resonance thermometry from phase-sensitive images. There were no significant differences between baseline and 3-mo mean American Urological Association Symptom Score or Sexual Health Inventory in Men scores. No man required pads at any time. Overall, the mean PSA decrease between baseline and 3 mo was 2.3 ng/ml (44.2%). Of 28 sites subjected to target biopsy after FLA, 26 (96%) showed no evidence of PCA. Our study provides encouraging evidence that excellent early oncologic control of significant PCA can be achieved following FLA, with virtually no complications or adverse impact on quality of life. Longer follow-up is required to show that oncologic control is durable. Patient summary Early results for focal laser ablation of prostate cancer are very encouraging. Until long-term oncologic control is demonstrated, focal laser ablation must be considered an investigational treatment option. © 2015 European Association of Urology.


Seyedmousavi S.,Radboudumc | Mouton J.W.,Radboudumc | Melchers W.J.G.,Radboudumc | Bruggemann R.J.M.,Radboudumc | Verweij P.E.,Radboudumc
Drug Resistance Updates | Year: 2014

Azole resistance is an emerging problem in Aspergillus fumigatus and is associated with a high probability of treatment failure. An azole resistance mechanism typically decreases the activity of multiple azole compounds, depending on the mutation. As alternative treatment options are limited and in some isolates the minimum inhibitory concentration (MIC) increases by only a few two-fold dilutions steps, we investigated if voriconazole and posaconazole have a role in treating azole-resistant Aspergillus disease. The relation between resistance genotype and phenotype, pharmacokinetic and pharmacodynamic properties, and (pre)clinical treatment efficacy were reviewed. The results were used to estimate the exposure needed to achieve the pharmacodynamic target for each MIC. For posaconazole adequate exposure can be achieved only for wild type isolates as dose escalation does not allow PD target attainment. However, the new intravenous formulation might result in sufficient exposure to treat isolates with a MIC of 0.5 mg/L. For voriconazole our analysis indicated that the exposure needed to treat infection due to isolates with a MIC of 2 mg/L is feasible and maybe isolates with a MIC of 4 mg/L. However, extreme caution and strict monitoring of drug levels would be required, as the probability of toxicity will also increase. © 2014 Elsevier Ltd. All rights reserved.


Muller A.E.,Radboudumc | Punt N.,Radboudumc | Mouton J.W.,Radboudumc
Antimicrobial agents and chemotherapy | Year: 2014

The percentage of the dosing interval that the non-protein-bound plasma concentration is above the MIC (%fT>MIC) for cephalosporins has been shown to correlate with microbiological outcomes in preclinical studies. However, clinical data are scarce. Using data from a randomized double-blind phase 3 clinical trial, we explored the relationship of ceftobiprole exposure with microbiological and clinical outcomes in patients with nosocomial pneumonia. The individual ceftobiprole exposure was determined for different pharmacokinetic (PK)/pharmacodynamic (PD) indices using individual pharmacokinetic data and a previously published population model. The MICs used in the analysis were the highest MICs for any bacterium cultured at baseline or the end of treatment (EOT). Outcomes were microbiological cure at EOT and clinical cure at test of cure (TOC). Multiple logistic regression (MLR) and classification and regression tree (CART) analyses were applied to determine the relationships among exposure, patient characteristics, and outcomes. MLR indicated that the %fT>MIC of ceftobiprole was the best predictor for both microbiological eradication and clinical cure. CART analysis showed a breakpoint value of 51.1% (n = 159; P = 0.0024) for clinical cure, whereas it was 62.2% (n = 251; P < 0.0001) for microbiological eradication. Other factors also contributed, particularly to clinical outcome. These included the difference between VAP and non-VAP patients, systemic inflammatory response syndrome (SIRS), creatinine clearance, the use of anti-Pseudomonas combination therapy, and Acute Physiology and Chronic Health Evaluation II (APACHE-II) score. There is a strong correlation between microbiological eradication and clinical cure with exposure to ceftobiprole. The %fT>MIC required to result in a favorable clinical outcome is >51% of the dosing interval, which is in line with the values found for microbiological eradication, the comparator ceftazidime, and preclinical models.


News Article | December 15, 2016
Site: www.rdmag.com

RadboudUMC, one of the largest and leading Academic Medical Centers in The Netherlands, has reported on its effective use of the Micronic Univo Screw Cap Recapper SR096 to securely seal its valuable DNA samples. Mr Alwin Rikken, Operational Manager of the Central Genome Analysis Laboratory (CGAL) at the Human Genetics Department – Genome Diagnostics, praises its affordability and reliability. The CGAL conducts research on the relation between genes and diseases. Using advanced analysing techniques, the CGAL provides high quality and up-to-date prenatal and postnatal diagnostics of genetic disorders for patients and their families. The Genome Analysis Laboratory is equipped with the latest technologies to perform various types of diagnostic services. The entire Genome Diagnostics division performs over 25.000 tests each year. By offering the CGAL a timesaving recapping solution, Micronic experts help them advance their important and meaningful research. The CGAL plans to expand their diagnostic capabilities. Rikken said: “We are planning to store 400.000 DNA samples at the end of the year. At the moment we have an automated storage system with a capacity of almost 400.000 samples. We are working on a new storage system with a capacity of 1.4 million samples.” In the future, the CGAL wants to store the DNA samples of its Research Department and the RadboudUMC Biobank, along with the DNA samples of Genome Diagnostics. Since the CGAL is growing, the Micronic Univo Screw Cap Recapper SR096 is very suited to make the work in the laboratory faster and easier. The Recapper is able to cap, decap or recap 96 tubes in a single action, and decaps Screw Caps from a full 96-tube storage rack in less than 30 seconds. Through the graphical touch screen interface the operator is able to select any rack to cap, decap or recap without using different adapters for different tube sizes. The Screw Cap Recapper uses a precisely determined torque value for optimal sealing quality thereby minimizing sample evaporation and maximizing the integrity of samples. Mr Rikken would recommend the Micronic Univo Screw Cap Recapper SR096 to other labs: “It is a very smoothly running, easy to use and silent device. I also think it is a great benefit that the Screw Cap Recapper is contamination-free.” The Screw Cap Recapper SR096 is also compatible for use with other brands of tubes and caps. This means that it is possible to use sample storage tubes or caps from another brand, and still benefit from the wide range of qualities the Recapper SR096 features.

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