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MacKenbach J.P.,Rotterdam University | Karanikolos M.,London School of Hygiene and Tropical Medicine | McKee M.,London School of Hygiene and Tropical Medicine
The Lancet | Year: 2013

Europe, with its 53 countries and divided history, is a remarkable but inadequately exploited natural laboratory for studies of the effects of health policy. In this paper, the first in a Series about health in Europe, we review developments in population health in Europe, with a focus on trends in mortality, and draw attention to the main successes and failures of health policy in the past four decades. In western Europe, life expectancy has improved almost continuously, but progress has been erratic in eastern Europe, and, as a result, disparities in male life expectancy between the two areas are greater now than they were four decades ago. The falls in mortality noted in western Europe are associated with many different causes of death and show the combined effects of economic growth, improved health care, and successful health policies (eg, tobacco control, road traffic safety). Less favourable mortality trends in eastern Europe show economic and health-care problems and a failure to implement effective health policies. The political history of Europe has left deep divisions in the health of the population. Important health challenges remain in both western and eastern Europe and signify unresolved issues in health policy (eg, alcohol, food) and rising health inequalities within countries. © 2013 Elsevier Ltd.


Hazes J.M.,Rotterdam University
Rheumatology (Oxford, England) | Year: 2011

It has long been known that pregnancy and childbirth have a profound effect on the disease activity of rheumatic diseases. For clinicians, the management of patients with RA wishing to become pregnant involves the challenge of keeping disease activity under control and adequately adapting drug therapy during pregnancy and post-partum. This article aims to summarize the current evidence on the evolution of RA disease activity during and after pregnancy and the use of anti-rheumatic drugs around this period. Of recent interest is the potential use of anti-TNF compounds in the preconception period and during pregnancy. Accumulating experience with anti-TNF therapy in other immune-mediated inflammatory diseases, such as Crohn's disease, provides useful insights for the use of TNF blockade in pregnant women with RA, or RA patients wishing to become pregnant.


Information about the influence of delayed surgery on infectious wound complications is ambiguous. A clinical audit was performed to test the hypothesis that early surgery lowers the rate of infectious wound complications. Secondly we looked at the influence of surgical delay and complications on patient reported functional outcome. All consecutive, closed distal fibular fractures treated surgically with a plate were included and retrospectively analysed for the delay in operation and wound complications. In a second cohort of patients with a AO-Weber B-type ankle fracture outcome was measured using the Olerud-Molander ankle score (OMAS), the American Orthopaedic Foot and Ankle Society score (AOFAS) and a visual analog score (VAS) for overall satisfaction. Patients treated within one day experienced no wound complications (zero out of 60), whereas in the delayed group 11% (16/145) did (p = 0.004). A similar significant difference was found for the patients treated within one week (2/98) versus after one week (14/107). A systematic review of the literature showed a difference in wound complications of 3.6% (early) versus 12.9% (late) (p < 0.0001). After 43 months, the median AOFAS was 11.5 points lower in the complication group, the OMAS 10 points, and the VAS 0.5 points, with all differences being statistically significant. Every effort should be made to operate on closed ankle fractures as soon as reasonably possible. A delay in surgery is associated with a significant rise in infectious wound complications, which significantly lowers outcome and patient satisfaction. These fractures should preferably be treated within the first day.


Bone marrow-derived mesenchymal stem cells (MSCs) have demonstrated potential for regenerative medicine strategies. Knowledge of the way these cells respond to their environment in in vitro culture and after implantation in vivo is crucial for successful therapy. Oxygen tension plays a pivotal role in both situations. In vivo, a hypoxic environment can lead to apoptosis, but hypoxic preconditioning of MSCs and overexpression of prosurvival genes like Akt can reduce hypoxia-induced cell death. In cell culture, hypoxia can increase proliferation rates and enhance differentiation along the different mesenchymal lineages. Hypoxia also modulates the paracrine activity of MSCs, causing upregulation of various secretable factors, among which are important angiogenic factors such as vascular endothelial growth factor and interleukin-6 (IL6). Finally, hypoxia plays an important role in mobilization and homing of MSCs, primarily by its ability to induce stromal cell-derived factor-1 expression along with its receptor CXCR4. This article reviews the current literature on the effects of hypoxia on MSCs and aims to elucidate its potential role in regenerative medicine strategies.


Fakhry F.,Rotterdam University
Journal of vascular surgery | Year: 2012

Exercise therapy is a common intervention for the management of intermittent claudication (IC). However, considerable uncertainty remains about the effect of different exercise components such as intensity, duration, or content of the exercise programs. The aim of this study was to assess the effectiveness of supervised walking therapy (SWT) as treatment in patients with IC and to update and identify the most important exercise components resulting in an optimal training protocol for patients with IC. A systematic literature search using MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials databases was performed. Randomized controlled trials (RCTs) published between January 1966 and February 2012 were included if they evaluated the effectiveness of SWT. Predefined exercise components were extracted, including treadmill use during training, claudication pain end point used during walking, length of the SWT program, and total training volume. A meta-analysis and meta-regression was performed to evaluate the weighted mean difference in maximum walking distance (MWD) and pain-free walking distance (PFWD) between SWT and noninterventional observation. Twenty-five RCTs (1054 patients) comparing SWT vs noninterventional observation showed a weighted mean difference of 180 meters (95% confidence interval, 130-230 meters) in MWD and 128 meters (95% confidence interval, 92-165 meters) in PFWD, both in favor of the SWT group. In multivariable meta-regression analysis, none of the predefined exercise components were independently associated with significant improvements in MWD or PFWD. SWT is effective in improving MWD and PFWD in patients with IC. However, pooled results from the RCTs did not identify any of the exercise components including intensity, duration, or content of the program as being independently associated with improvements in MWD or PFWD. Copyright © 2012 Society for Vascular Surgery. All rights reserved.


Van Der Heijden M.,Rotterdam University
Proceedings of the National Academy of Sciences of the United States of America | Year: 2014

This study analyzes a waveguide consisting of two parallel fluidfilled chambers connected by a narrow slit that is spanned by two coupled elastic beams. A stiffness gradient exists in the longitudinal direction. This simple linear system, which contains no lumped mass, is shown to act as a spectral analyzer. Fluid waves traveling in the waveguide exhibit a distinct amplitude peak at a longitudinal location that varies systematically with frequency. The peaking is not based on resonance, but entirely on wave dispersion. When entering its peak region, the wave undergoes a sharp deceleration associated with a transition in which two propagation modes exchange roles. It is proposed that this mode shape swapping underlies the frequency analysis of the mammalian cochlea.


Ince C.,Rotterdam University
Current Opinion in Critical Care | Year: 2014

Purpose of Review: The ultimate purpose of fluid administration in states of hypovolemia is to correct cardiac output to improve microcirculatory perfusion and tissue oxygenation. Observation of the microcirculation using handheld microscopes gives insight into the nature of convective and diffusive defect in hypovolemia. The purpose of this article is to introduce a new platform for hemodynamic-targeted fluid therapy based on the correction of tissue and microcirculatory perfusion assumed to be at risk during hypovolemia. Recent Findings: Targeting systemic hemodynamic targets and/or clinical surrogates of hypovolemia gives inadequate guarantee for the correction of tissue perfusion by fluid therapy especially in conditions of distributive shock as occur in inflammation and sepsis. Findings are presented, which support the idea that only clinical signs of hypovolemia associated with low microcirculatory flow can be expected to benefit from fluid therapy and that fluid overload causes a defect in the diffusion of oxygen transport. Summary: We hypothesized that the optimal amount of fluid needed for correction of hypovolemia is defined by a physiologically based functional microcirculatory hemodynamic platform where convection and diffusion need to be optimized. Future clinical trials using handheld microscopes able to automatically evaluate the microcirculation at the bedside will show whether such a platform will indeed optimize fluid therapy. © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Purpose: Recently, a new suture-button fixation device has emerged for the treatment of acute distal tibiofibular syndesmotic injuries and its use is rapidly increasing. The current systematic review was undertaken to compare the biomechanical properties, functional outcome, need for implant removal, and the complication rate of syndesmotic disruptions treated with a suture-button device with the current 'gold standard', i.e. the syndesmotic screw. Method: A literature search in the electronic databases of the Cochrane Library, EMbase, Pubmed Medline, and Google Scholar, between January 1st 2000 to December 1st 2011, was conducted to identify studies in which unstable ankle fractures with concomitant distal tibiofibular syndesmotic injury were treated with either a syndesmotic screw or a suture-button device. Results: A total of six biomechanical studies, seven clinical full-text studies and four abstracts on the TightRope system, and 27 studies on syndesmotic screw or bolt fixation were identified. TheAOFAS of 133 patients treated with TightRope was 89.1 points, with an average study follow-up of 19 months. The AOFAS score in studies with 253 patients treated with syndesmotic screws (metallic and absorbable) or bolts was 86.3 points, with an average study follow-up of 42 months. Two studies reported an earlier return to work in the TightRope group. Implant removal was reported in 22 (10%) of 220 patients treated with a TightRope (range, 0-25%), in the screw or bolt group the average was 51.9% of 866 patients (range, 5.8-100%). Conclusion: The TightRope system has a similar outcome compared with the syndesmotic screw or bolt fixation, but might lead to a quicker return to work. The rate of implant removal is lower than in the syndesmotic screw group. There is currently insufficient evidence on the long-term effects of the TightRope and more uniform outcome reporting is desirable. In addition, there is a need for studies on cost-effectiveness of the treatment of acute distal tibiofibular syndesmotic disruption treated with a suture-button device. © The Author(s) 2012.


Patent
Rotterdam University | Date: 2014-01-08

A wheel suspension for a steering wheel (10) comprises a wheel holder (30..33) with which the wheel is rotatably connected. The wheel holder is coupled to the vehicle frame (20) in a swivelable manner through the interposition of the wheel suspension. The wheel suspension comprises a set of rail bodies (41, 42) and a set of swivel bodies (43, 44) which are rotatably connected in relation to each other and to the wheel holder (30). The rail bodies (41, 42) engage with the wheel holder (30..33) in particular on both sides of the wheel outside a wheel space. Thus the wheel suspension brings about a steering of the wheel (10) around a supporting point (S), while space is available within the wheel for placement of say a wheel motor (80).


Borst J.G.G.,Rotterdam University
Trends in Neurosciences | Year: 2010

The release probability, the average probability that an active zone of a presynaptic terminal releases one or more vesicles following an action potential, is tightly regulated. Measurements in cultured neurons or in slices indicate that this probability can vary greatly between synapses, but on average it is estimated to be as high as 0.5. In vivo, however, the size of synaptic potentials is relatively independent of recent history, suggesting that release probability is much lower. Possible causes for this discrepancy include maturational differences, a higher spontaneous activity, a lower extracellular calcium concentration and more prominent tonic inhibition by ambient neurotransmitters during in vivo recordings. Existing evidence thus suggests that under physiological conditions in vivo, presynaptic action potentials trigger the release of neurotransmitter much less frequently than what is observed in in vitro preparations. © 2010 Elsevier Ltd.

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