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Rovers M.M.,UMC St Radboud
Nederlands tijdschrift voor geneeskunde | Year: 2012

An IPD (Individual Participant Data) meta-analysis requires collecting original individual patient data and calculating an estimated effect based on these data. The use of individual patient data has various advantages: the original data and the results of published analyses are verified, comparability between studies in terms of definitions, coding and analyses is increased, the number of options for performing sub-group analyses becomes greater, and it becomes possible to conduct more complex statistical analyses, such as the pooling of time-dependent data and multivariate regression analyses. In an IPD meta-analysis, additional information can be used which was not mentioned in the original article, for example, data from long-term follow-up. Improvements to this methodology are still possible; for example, to find the right balance between sufficient power to detect clinically relevant subgroup effects and minimizing the risk of false-positive findings. Readers can evaluate an IPD meta-analysis on various factors, including the reason for the choice for an IPD meta-analysis, the method used to identify and select the studies, and the number of approached authors that made their data available.


Van Kampen J.J.A.,Laboratories of Neuro Oncology Clinical and Cancer Proteomics | Burgers P.C.,Laboratories of Neuro Oncology Clinical and Cancer Proteomics | De Groot R.,UMC St Radboud | Gruters R.A.,Erasmus University Rotterdam | Luider T.M.,Laboratories of Neuro Oncology Clinical and Cancer Proteomics
Mass Spectrometry Reviews | Year: 2011

Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS) is an emerging analytical tool for the analysis of molecules with molar masses below 1,000 Da; that is, small molecules. This technique offers rapid analysis, high sensitivity, low sample consumption, a relative high tolerance towards salts and buffers, and the possibility to store sample on the target plate. The successful application of the technique is, however, hampered by low molecular weight (LMW) matrix-derived interference signals and by poor reproducibility of signal intensities during quantitative analyses. In this review, we focus on the biomedical application of MALDI-MS for the analysis of small molecules and discuss its favorable properties and its challenges as well as strategies to improve the performance of the technique. Furthermore, practical aspects and applications are presented. © 2010 Wiley Periodicals, Inc.


De Luca G.,University of Piemonte Orientale | Verdoia M.,University of Piemonte Orientale | Suryapranata H.,UMC St Radboud
Atherosclerosis | Year: 2012

Background: Adjunctive abciximab administration has been demonstrated to reduce mortality and reinfarction in patients with ST-elevation myocardial infarction (STEMI) referred to invasive management. Standard abciximab regimen consists of an intravenous (IV) bolus followed by a 12-h IV infusion. Experimental studies and small clinical trials suggest the superiority of intracoronary (IC) injection of abciximab over IV route. Therefore, the aim of the current study was to perform a meta-analysis of randomized trials (RCTs) to assess the clinical efficacy and safety of IC vs IV abciximab administration in STEMI patients undergoing primary angioplasty. Methods: We obtained results from all RCTs enrolling STEMI patients undergoing primary percutaneous coronary intervention (PCI). The primary endpoint was mortality, while recurrent myocardial infarction, postprocedural epicardial (TIMI 3) and myocardial (MBG 2-3) perfusion were identified as secondary endpoints. The safety endpoint was the risk of major bleeding complications. Results: A total of 8 randomized trials were finally included in the meta-analysis, enrolling a total of 3259 patients. As compared to IV route, IC abciximab was associated with a significant improvement in myocardial perfusion (OR [95% CI] = 1.76 [1.28-2.42], p< 0.001), without significant benefits in terms of mortality (OR [95% CI] = 0.85 [0.59-1.23], p= 0.39), reinfarction (OR [95% CI] = 0.79 [0.46-1.33], p= 0.37), or major bleeding complications (OR [95% CI] = 1.19 [0.76-1.87], p= 0.44). However, we observed a significant relationship between patient's risk profile and mortality benefits from IC abciximab administration (p= 0.011). Conclusions: The present updated meta-analysis showed that IC administration of abciximab is associated with significant benefits in myocardial perfusion, but not in clinical outcome at short-term follow-up as compared to IV abciximab administration, without any excess of major bleedings in STEMI patients undergoing primary PCI. However, a significant relationship was observed between patient's risk profile and mortality benefits from IC abciximab administration. Therefore, waiting for long-term follow-up results and additional randomized trials, IC abciximab administration cannot be routinely recommended, but may be considered in high-risk patients. © 2012 Elsevier Ireland Ltd.


Verbeek A.L.,UMC St Radboud
Nederlands tijdschrift voor geneeskunde | Year: 2013

Annually, in the Netherlands around 900,000 women between the ages of 50-75 years undergo mammography as part of a population screening into breast cancer. In this way more than 5000 cases of breast cancer are detected (0.6% of women screened); 70% of these malignancies are < stage II, which is prognostically favourable. Due to the early detection and treatment of breast cancer, the breast cancer death risk in those women who participate in the population screening is half that of women who choose not to be screened. The downside of the population screening is that participants are relatively often referred to a hospital for a diagnostic work-up (around 2%), and 70% of them are ultimately found not to have cancer. The positive predictive value of the population screening is 30%. Early discovery also leads to over-diagnosis in patients with breast cancer that without screening would never have manifested itself. Based on computer simulations it has been estimated that in the Netherlands over-diagnosis occurs in 9% of patients in whom breast cancer is detected during a population screening.


Keijmel S.P.,UMC St Radboud
Nederlands tijdschrift voor geneeskunde | Year: 2012

In the Netherlands, more than 4000 patient cases of acute Q fever have been reported since 2007. Approximately 20% of these patients subsequently developed long-term fatigue. Such fatigue, as well as other physical symptoms and patient-perceived limitations in social functioning, have been compiled into what is known as the Q fever fatigue syndrome (QFS). The number of Dutch patients having QFS is expected to increase over the next years. The chance of a spontaneous recovery during the first six months following an acute Q fever infection is high. Allowing the fatigue to run its natural course is therefore justified. The diagnosis of QFS is based on history-taking, a physical examination and laboratory test results. The percentage of patients who recover spontaneously from QFS seems low. Data on outcome after treatment are not yet available. The recommendation is to refer patients with QFS to specialists who offer cognitive behavioural therapy for chronic fatigue syndrome or QFS. The objective of the recently published national guideline 'Q fever fatigue syndrome (QFS)' is to achieve uniformity in its diagnosis and treatment.

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