Palliative care in heart failure: a position statement from the palliative care workshop of the Heart Failure Association of the European Society of Cardiology

Heart failure is a serious condition and equivalent to malignant disease in terms of symptom burden and mortality. At this moment only a comparatively small number of heart failure patients receive specialist palliative care. Heart failure patients may have generic palliative care needs, such as refractory multifaceted symptoms, communication and decision making issues and the requirement for family support. The Advanced Heart Failure Study Group of the Heart Failure Association of the European Society of Cardiology organized a workshop to address the issue of palliative care in heart failure to increase awareness of the need for palliative care. Additional objectives included improving the accessibility and quality of palliative care for heart failure patients and promoting the development of heart failure-orientated palliative care services across Europe. This document represents a synthesis of the presentations and discussion during the workshop and describes recommendations in the area of delivery of quality care to patients and families, education, treatment coordination, research and policy.

Effect of detraining on bone and muscle tissue in subjects with chronic spinal cord injury after a period of electrically-stimulated cycling: a small cohort study

OBJECTIVE: To investigate adaptive changes in bone and muscle parameters in the paralysed limbs after detraining or reduced functional electrical stimulation (FES) induced cycling following high-volume FES-cycling in chronic spinal cord injury. SUBJECTS: Five subjects with motor-sensory complete spinal cord injury (age 38.6 years, lesion duration 11.4 years) were included. Four subjects stopped FES-cycling completely after the training phase whereas one continued reduced FES-cycling (2-3 times/week, for 30 min). METHODS: Bone and muscle parameters were assessed in the legs using peripheral quantitative computed tomography at 6 and 12 months after cessation of high-volume FES-cycling. RESULTS: Gains achieved in the distal femur by high-volume FES-cycling were partly maintained at one year of detraining: 73.0% in trabecular bone mineral density, 63.8% in total bone mineral density, 59.4% in bone mineral content and 22.1% in muscle cross-sectional area in the thigh. The subject who continued reduced FES-cycling maintained 96.2% and 95.0% of the previous gain in total and trabecular bone mineral density, and 98.5% in muscle cross-sectional area. CONCLUSION: Bone and muscle benefits achieved by one year of high-volume FES-cycling are partly preserved after 12 months of detraining, whereas reduced cycling maintains bone and muscle mass gained. This suggests that high-volume FES-cycling has clinical relevance for at least one year after detraining.

Regioselective preparation of 5-hydroxypropranolol and 4'-hydroxydiclofenac with a fungal peroxygenase

An extracellular peroxygenase of Agrocybe aegerita catalyzed the H(2)O(2)-dependent hydroxylation of the multi-function beta-adrenergic blocker propranolol (1-naphthalen-1-yloxy-3-(propan-2-ylamino)propan-2-ol) and the non-steroidal anti-inflammatory drug diclofenac (2-[2-[(2,6-dichlorophenyl)amino]phenyl]acetic acid) to give the human drug metabolites 5-hydroxypropranolol (5-OHP) and 4'-hydroxydiclofenac (4'-OHD). The reactions proceeded regioselectively with high isomeric purity and gave the desired 5-OHP and 4'-OHD in yields up to 20% and 65%, respectively. (18)O-labeling experiments showed that the phenolic hydroxyl groups in 5-OHP and 4'-OHD originated from H(2)O(2), which establishes that the reaction is mechanistically a peroxygenation. Our results raise the possibility that fungal peroxygenases may be useful for versatile, cost-effective, and scalable syntheses of drug metabolites.

Evaluation of a Bayesian MCMC Random Effects Inference Methodology for Capture-Mark-Recapture Data

Monte Carlo simulation was used to evaluate properties of a simple Bayesian MCMC analysis of the random effects model for single group Cormack-Jolly-Seber capture-recapture data. The MCMC method is applied to the model via a logit link, so parameters p, S are on a logit scale, where logit(S) is assumed to have, and is generated from, a normal distribution with mean μ and variance σ2 . Marginal prior distributions on logit(p) and μ were independent normal with mean zero and standard deviation 1.75 for logit(p) and 100 for μ ; hence minimally informative. Marginal prior distribution on σ2 was placed on τ2=1/σ2 as a gamma distribution with α=β=0.001 . The study design has 432 points spread over 5 factors: occasions (t) , new releases per occasion (u), p, μ , and σ . At each design point 100 independent trials were completed (hence 43,200 trials in total), each with sample size n=10,000 from the parameter posterior distribution. At 128 of these design points comparisons are made to previously reported results from a method of moments procedure. We looked at properties of point and interval inference on μ , and σ based on the posterior mean, median, and mode and equal-tailed 95% credibility interval. Bayesian inference did very well for the parameter μ , but under the conditions used here, MCMC inference performance for σ was mixed: poor for sparse data (i.e., only 7 occasions) or σ=0 , but good when there were sufficient data and not small σ .

Executive Stock Ownership and Performance: Tracking Faint Traces

We examine the relation between managers' financial interests and firm performance. Since the relation could go in either direction, we cast the analysis in a simultaneous equations framework. For firms involved in acquisitions, we find that acquisition performance and Tobin's Q ratios affect the size of managers' stockholdings. We find no evidence, however, that larger stockholdings lead to better performance. Perhaps management is effectively disciplined by competition in product and labor markets. Alternatively, it may not be necessary for top executives to own stock to the residual claimants. And finally, higher ownership might multiply the opportunities to appropriate corporate wealth.

Executive compensation and the performance of the firm

A sample of large industrial corporations is examined to determine whether there is a relationship between the levels of compensation received by the senior executives of those firms and the firms' economic performances. We find consistent evidence of such a relationship, with differences across firms in the total compensation of their three highest-paid officers being positively related to differences in both the common stock returns and operating profitability of the firms. The implication is that compensation packages are designed to reduce agency costs.

Corporate acquisitions by listed firms: the experience of a comprehensive sample

The sample used includes tender offers, mergers, acquisitions of privately held corporations, and comprehensive acquisitions of other firms' assets. According to the results, the majority of bid announcements prompt significant stock price increases, especially when controlling for partial anticipation problems and relative acquisition size. Furthermore, there is little evidence that firms that engage in "bad" acquisitions are more likely to be taken over.

Executive compensation and executive incentive problems: an empirical analysis

The question of whether the design of the corporate executive pay package reflects an attempt to reduce agency costs between shareholders an managers is adressed. The components of senior executive pay are found to vary systematically across firms in a manner that cannot easily be explained by tax effects, and which would indicate that individual elements of pay are aimed at controlling for limited horizon and risk exposure problems. Managerial decisions and the structure of managerial pay therefore appear to be interrelated.

Effects of Chemical Composition on Forage Intake of Heifers Fed Hays of Different Species

Alfalfa, smooth bromegrass, and big bluestem hays harvested at two maturities differing by four weeks were fed at mature-to-immature hay ratios of 1:0, 2:1, 1:2, and 0:1 to yearling heifers in an experiment with a three 4 x 4 Latin square design with 14 day periods. Concentrations of in vitro digestible dry matter and crude protein were greater and concentrations of neutral detergent fiber, acid detergent fiber, and indigestible neutral detergent fiber (determined by either a manual method with a 96 hour incubation or an automated method with a 48 hour incubation) were less in alfalfa hay than in the two grass hays and in smooth bromegrass hay than in big bluestem hay. Concentrations of in vitro digestible dry matter and crude protein decreased whereas those of neutral detergent fiber, acid detergent fiber and indigestible neutral detergent fiber increased with increasing forage maturity. Consumptions of dry matter, digestible dry matter, in vitro digestible dry matter, and crude protein were greater for heifers fed alfalfa hay diets than those fed the two grasses. Consumptions of total neutral detergent fiber and indigestible neutral detergent fiber, determined by the automated method with a 48 hour incubation, were greater by heifers fed diets containing big bluestem than those fed alfalfa or smooth bromegrass diets. Consumptions of acid detergent fiber and indigestible neutral detergent fiber, determined by a manual method with a 96 hour incubation, were greater for heifers fed alfalfa or big bluestem hay diets than those of heifers fed smooth bromegrass diets. Consumption of dry matter, in vivo or in vitro digestible dry matter, crude protein, neutral detergent fiber, acid detergent fiber and automated indigestible neutral detergent fiber decreased as the mature-to-immature hay ratio decreased. Diet digestibility was not affected by forage species, but increased as the mature-toimmature hay ratio decreased. Fecal excretion of dry matter and neutral detergent fiber did not differ between forage species or mature-to-immature hay ratios. Forage dry matter intake expressed as a percentage of body weight was significantly related to the concentrations of in vitro digestible dry matter (r2=.14), crude protein (r2=.17), neutral detergent fiber (r2=.20), and manual indigestible neutral detergent fiber (r2=.18) of the hays and the concentration of digestible dry matter of the diets (r2=.43).