One year cost effectiveness of sirolimus eluting stents compared with bare metal stents in the treatment of single native de novo coronary lesions: an analysis from the RAVEL trial

OBJECTIVE: To assess the balance between costs and effects of the sirolimus eluting stent in the treatment of single native de novo coronary lesions in the RAVEL (randomised study with the sirolimus eluting Bx Velocity balloon expandable stent in the treatment of patients with de novo native coronary artery lesions) study. DESIGN: Multicentre, double blind, randomised trial. SETTING: Percutaneous coronary intervention for single de novo coronary lesions. PATIENTS: 238 patients with stable or unstable angina. INTERVENTIONS: Randomisation to sirolimus eluting stent or bare stent implantation. MAIN OUTCOME MEASURES: Patients were followed up to one year and the treatment effects were expressed as one year survival free of major adverse cardiac events (MACE). Costs were estimated as the product of resource utilisation and Dutch unit costs. RESULTS: At one year, the absolute difference in MACE-free survival was 23% in favour of the sirolimus eluting stent group. At the index procedure, sirolimus eluting stent implantation had an estimated additional procedural cost of 1286. At one year, however, the estimated additional cost difference had decreased to 54 because of the reduction in the need for repeat revascularisations in the sirolimus group (0.8% v 23.6%; p < 0.01). After adjustment of actual results for the consequences of angiographic follow up (correction based on data from the BENESTENT (Belgium Netherlands stent) II study), the difference in MACE-free survival was estimated at 11.1% and the addit

Shot noise in mesoscopic systems

This is a review of shot noise, the time-dependent fluctuations in the electrical current due to the discreteness of the electron charge, in small conductors. The shot-noise power can be smaller than that of a Poisson process as a result of correlations in the electron transmission imposed by the Pauli principle. This suppression takes on simple universal values in a symmetric double-barrier junction (suppression factor 1/2), a disordered metal (factor 1/3), and a chaotic cavity (factor 1/4). Loss of phase coherence has no effect on this shot-noise suppression, while thermalization of the electrons due to electron-electron scattering increases the shot noise slightly. Sub-Poissonian shot noise has been observed experimentally. So far unobserved phenomena involve the interplay of shot noise with the Aharonov-Bohm effect, Andreev reflection, and the fractional quantum Hall effect.Comment: 37 pages, Latex, 10 figures (eps). To be published in "Mesoscopic Electron Transport," edited by L. P. Kouwenhoven, G. Schoen, and L. L. Sohn, NATO ASI Series E (Kluwer Academic Publishing, Dordrecht

Brain and ventricular volume in patients with syndromic and complex craniosynostosis

textabstractPurpose: Brain abnormalities in patients with syndromic craniosynostosis can either be a direct result of the genetic defect or develop secondary to compression due to craniosynostosis, raised ICP or hydrocephalus. Today it is unknown whether children with syndromic craniosynostosis have normal brain volumes. The purpose of this study was to evaluate brain and ventricular volume measurements in patients with syndromic and complex craniosynostosis. This knowledge will improve our understanding of brain development and the origin of raised intracranial pressure in syndromic craniosynostosis. Methods: Brain and ventricular volumes were calculated from MRI scans of patients with craniosynostosis, 0.3 to 18.3 years of age. Brain volume was compared to age matched controls from the literature. All patient charts were reviewed to look for possible predictors of brain and ventricular volume. Results: Total brain volume in syndromic craniosynostosis equals that of normal controls, in the age range of 1 to 12 years. Brain growth occurred particularly in the first 5 years of age, after which it stabilized. Within the studied population, ventricular volume was significantly larger in Apert syndrome compared to all other syndromes and in patients with a Chiari I malformation. Conclusions: Patients with syndromic craniosynostosis have a normal total brain volume compared to normal controls. Increased ventricular volume is associated with Apert syndrome and Chiari I malformations, which is most commonly found in Crouzon syndrome. We advice screening of all patients with Apert and Crouzon syndrome for the development of enlarged ventricle volume and the presence of a Chiari I malformation

Genotype by environment interaction for 450-day weight of Nelore cattle analyzed by reaction norm models

Genotype by environment interactions (GEI) have attracted increasing attention in tropical breeding programs because of the variety of production systems involved. In this work, we assessed GEI in 450-day adjusted weight (W450) Nelore cattle from 366 Brazilian herds by comparing traditional univariate single-environment model analysis (UM) and random regression first order reaction norm models for six environmental variables: standard deviations of herd-year (RRMw) and herd-year-season-management (RRMw-m) groups for mean W450, standard deviations of herd-year (RRMg) and herd-year-season-management (RRMg-m) groups adjusted for 365-450 days weight gain (G450) averages, and two iterative algorithms using herd-year-season-management group solution estimates from a first RRMw-m and RRMg-m analysis (RRMITw-m and RRMITg-m, respectively). The RRM results showed similar tendencies in the variance components and heritability estimates along environmental gradient. Some of the variation among RRM estimates may have been related to the precision of the predictor and to correlations between environmental variables and the likely components of the weight trait. GEI, which was assessed by estimating the genetic correlation surfaces, had values < 0.5 between extreme environments in all models. Regression analyses showed that the correlation between the expected progeny differences for UM and the corresponding differences estimated by RRM was higher in intermediate and favorable environments than in unfavorable environments (p < 0.0001)

Older adult loneliness: myths and realities

The focus in this paper is on the social domain of quality of life, and more particularly loneliness. The empirical literature on older adult loneliness is reviewed, thereby challenging three often-held assumptions that figure prominently in public debates on loneliness. The first assumption that loneliness is a problem specifically for older people finds only partial support. Loneliness is common only among the very old. The second assumption is that people in individualistic societies are most lonely. Contrary to this belief, findings show that older adults in northern European countries tend to be less lonely than those in the more familialistic southern European countries. The scarce data on Central and Eastern Europe suggest a high prevalence of older adult loneliness in those countries. The third assumption that loneliness has increased over the past decades finds no support. Loneliness levels have decreased, albeit slightly. The review notes the persistence of ageist attitudes, and underscores the importance of considering people’s frame of reference and normative orientation in analyses of loneliness

Recovery from Posttraumatic Stress Symptoms: A Qualitative Study of Attributions in Survivors of War

This study was funded by a grant from the European Commission, contract number INCO-CT-2004-50917

Cerebral activations related to ballistic, stepwise interrupted and gradually modulated movements in parkinson patients

Patients with Parkinson's disease (PD) experience impaired initiation and inhibition of movements such as difficulty to start/stop walking. At single-joint level this is accompanied by reduced inhibition of antagonist muscle activity. While normal basal ganglia (BG) contributions to motor control include selecting appropriate muscles by inhibiting others, it is unclear how PD-related changes in BG function cause impaired movement initiation and inhibition at single-joint level. To further elucidate these changes we studied 4 right-hand movement tasks with fMRI, by dissociating activations related to abrupt movement initiation, inhibition and gradual movement modulation. Initiation and inhibition were inferred from ballistic and stepwise interrupted movement, respectively, while smooth wrist circumduction enabled the assessment of gradually modulated movement. Task-related activations were compared between PD patients (N = 12) and healthy subjects (N = 18). In healthy subjects, movement initiation was characterized by antero-ventral striatum, substantia nigra (SN) and premotor activations while inhibition was dominated by subthalamic nucleus (STN) and pallidal activations, in line with the known role of these areas in simple movement. Gradual movement mainly involved antero-dorsal putamen and pallidum. Compared to healthy subjects, patients showed reduced striatal/SN and increased pallidal activation for initiation, whereas for inhibition STN activation was reduced and striatal-thalamo-cortical activation increased. For gradual movement patients showed reduced pallidal and increased thalamo-cortical activation. We conclude that PD-related changes during movement initiation fit the (rather static) model of alterations in direct and indirect BG pathways. Reduced STN activation and regional cortical increased activation in PD during inhibition and gradual movement modulation are better explained by a dynamic model that also takes into account enhanced responsiveness to external stimuli in this disease and the effects of hyper-fluctuating cortical inputs to the striatum and STN in particular

Circulating markers of arterial thrombosis and late-stage age-related macular degeneration: a case-control study.

PURPOSE: The aim of this study was to examine the relation of late-stage age-related macular degeneration (AMD) with markers of systemic atherothrombosis. METHODS: A hospital-based case-control study of AMD was undertaken in London, UK. Cases of AMD (n=81) and controls (n=77) were group matched for age and sex. Standard protocols were used for colour fundus photography and to classify AMD; physical examination included height, weight, history of or treatment for vascular-related diseases and smoking status. Blood samples were taken for measurement of fibrinogen, factor VIIc (FVIIc), factor VIIIc, prothrombin fragment F1.2 (F1.2), tissue plasminogen activator, and von Willebrand factor. Odds ratios from logistic regression analyses of each atherothrombotic marker with AMD were adjusted for age, sex, and established cardiovascular disease risk factors, including smoking, blood pressure, body mass index, and total cholesterol. RESULTS: After adjustment FVIIc and possibly F1.2 were inversely associated with the risk of AMD; per 1 standard deviation increase in these markers the odds ratio were, respectively, 0.62 (95% confidence interval 0.40, 0.95) and 0.71 (0.46, 1.09). None of the other atherothrombotic risk factors appeared to be related to AMD status. There was weak evidence that aspirin is associated with a lower risk of AMD. CONCLUSIONS: This study does not provide strong evidence of associations between AMD and systematic markers of arterial thrombosis, but the potential effects of FVIIc, and F1.2 are worthy of further investigation

Loneliness, social support and cardiovascular reactivity to laboratory stress

Self-reported or explicit loneliness and social support have been inconsistently associated with cardiovascular reactivity (CVR) to stress. The present study aimed to adapt an implicit measure of loneliness, and use it alongside the measures of explicit loneliness and social support, to investigate their correlations with CVR to laboratory stress. Twenty-five female volunteers aged between 18 and 39 years completed self-reported measures of loneliness and social support, and an Implicit Association Test (IAT) of loneliness. The systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR) reactivity indices were measured in response to psychosocial stress induced in the laboratory. Functional support indices of social support were significantly correlated with CVR reactivity to stress. Interestingly, implicit, but not explicit, loneliness was significantly correlated with DBP reactivity after one of the stressors. No associations were found between structural support and CVR indices. Results are discussed in terms of validity of implicit versus explicit measures and possible factors that affect physiological outcomes

Impairment of Gradual Muscle Adjustment during Wrist Circumduction in Parkinson's Disease

Purposeful movements are attained by gradually adjusted activity of opposite muscles, or synergists. This requires a motor system that adequately modulates initiation and inhibition of movement and selectively activates the appropriate muscles. In patients with Parkinson's disease (PD) initiation and inhibition of movements are impaired which may manifest itself in e.g. difficulty to start and stop walking. At single-joint level, impaired movement initiation is further accompanied by insufficient inhibition of antagonist muscle activity. As the motor symptoms in PD primarily result from cerebral dysfunction, quantitative investigation of gradually adjusted muscle activity during execution of purposeful movement is a first step to gain more insight in the link between impaired modulation of initiation and inhibition at the levels of (i) cerebrally coded task performance and (ii) final execution by the musculoskeletal system. To that end, the present study investigated changes in gradual adjustment of muscle synergists using a manipulandum that enabled standardized smooth movement by continuous wrist circumduction. Differences between PD patients (N = 15, off-medication) and healthy subjects (N = 16) concerning the relation between muscle activity and movement performance in these groups were assessed using kinematic and electromyographic (EMG) recordings. The variability in the extent to which a particular muscle was active during wrist circumduction – defined as muscle activity differentiation - was quantified by EMG. We demonstrated that more differentiated muscle activity indeed correlated positively with improved movement performance, i.e. higher movement speed and increased smoothness of movement. Additionally, patients employed a less differentiated muscle activity pattern than healthy subjects. These specific changes during wrist circumduction imply that patients have a decreased ability to gradually adjust muscles causing a decline in movement performance. We propose that less differentiated muscle use in PD patients reflects impaired control of modulated initiation and inhibition due to decreased ability to selectively and jointly activate muscles