Cost-effectiveness of using hepatitis C viremic hearts for transplantation into HCV-negative recipients

Outcomes following hepatitis C virus (HCV)-viremic heart transplantation into HCV-negative recipients with HCV treatment are good. We assessed cost-effectiveness between cohorts of transplant recipients willing and unwilling to receive HCV-viremic hearts. Markov model simulated long-term outcomes among HCV-negative patients on the transplant waitlist. We compared costs (2018 USD) and health outcomes (quality-adjusted life-years, QALYs) between cohorts willing to accept any heart and those willing to accept only HCV-negative hearts. We assumed 4.9% HCV-viremic donor prevalence. Patients receiving HCV-viremic hearts were treated, assuming $39 600/treatment with 95% cure. Incremental cost-effectiveness ratios (ICERs) were compared to a $100 000/QALY gained willingness-to-pay threshold. Sensitivity analyses included stratification by blood type or region and potential negative consequences of receipt of HCV-viremic hearts. Compared to accepting only HCV-negative hearts, accepting any heart gained 0.14 life-years and 0.11 QALYs, while increasing costs by $9418/patient. Accepting any heart was cost effective (ICER $85 602/QALY gained). Results were robust to all transplant regions and blood types, except type AB. Accepting any heart remained cost effective provided posttransplant mortality and costs among those receiving HCV-viremic hearts were not >7% higher compared to HCV-negative hearts. Willingness to accept HCV-viremic hearts for transplantation into HCV-negative recipients is cost effective and improves clinical outcomes.     

Latency to enter a mirrored chamber: a novel behavioral assay for anxiolytic agents

Many animal species exhibit approach-avoidance responses upon the novel placement of a mirror into an individual animal's environment. With a view toward identifying new behavioral measures with qualitatively or quantitatively different responses to anxiolytic agents, we developed a mirrored chamber apparatus for which adult male BALB/cByJ mice showed an extended latency to enter. Administration of diazepam significantly reduced this latency to enter a mirrored chamber in a dosage-dependent manner. The psychomotor stimulant, methylphenidate, had no effect on latency to enter the mirrored chamber at a dose which stimulated locomotor activity to the same extent as diazepam. Thus, the decreased latency to enter the mirrored chamber brought about by diazepam seems unlikely to reflect the motor effects of this benzodiazepine. The potency of diazepam was significantly lower in the mirrored chamber assay than it was on three other measures of exploratory activity--"head-dipping" performance, plus-maze performance and locomotor activity stimulation. The findings of our study indicate that the mirrored chamber method is simple to carry out, nonpunishing, rapid and quantitative and that it possesses pharmacological attributes which distinguish its response to anxiolytics from other assays of exploratory behavior.     

Concurrent strength and endurance training. A review

Concurrent strength and endurance training appears to inhibit strength development when compared with strength training alone. Our understanding of the nature of this inhibition and the mechanisms responsible for it is limited at present. This is due to the difficulties associated with comparing results of studies which differ markedly in a number of design factors, including the mode, frequency, duration and intensity of training, training history of participants, scheduling of training sessions and dependent variable selection. Despite these difficulties, both chronic and acute hypotheses have been proposed to explain the phenomenon of strength inhibition during concurrent training. The chronic hypothesis contends that skeletal muscle cannot adapt metabolically or morphologically to both strength and endurance training simultaneously. This is because many adaptations at the muscle level observed in response to strength training are different from those observed after endurance training. The observation that changes in muscle fibre type and size after concurrent training are different from those observed after strength training provide some support for the chronic hypothesis. The acute hypothesis contends that residual fatigue from the endurance component of concurrent training compromises the ability to develop tension during the strength element of concurrent training. It is proposed that repeated acute reductions in the quality of strength training sessions then lead to a reduction in strength development over time. Peripheral fatigue factors such as muscle damage and glycogen depletion have been implicated as possible fatigue mechanisms associated with the acute hypothesis. Further systematic research is necessary to quantify the inhibitory effects of concurrent training on strength development and to identify different training approaches that may overcome any negative effects of concurrent training.     

Intimate combination of low- and high-resolution image data: I. Real-space PET and (1)H(2)O MRI, PETAMRI.

Two different types of (co-registered) images of the same slice of tissue will generally have different spatial resolutions. The judicious pixel-by-pixel combination of their data can be accomplished to yield a single image exhibiting properties of both. Here, axial (18)FDG PET and (1)H(2)O MR images of the human brain are used as the low- and high-resolution members of the pair. A color scale is necessary in order to provide for separate intensity parameters from the two image types. However, not all color scales can accommodate this separability. The HSV color model allows one to choose a color scale in which the intensity of the low-resolution image type is coded as hue, while that of the high-resolution type is coded as value, a reasonably independent parameter. Furthermore, the high-resolution image must have high contrast and be quantitative in the same sense as the low-resolution image almost always is. Here, relaxographic MR images (naturally segmented quantitative (1)H(2)O spin-density components) are used. Their essentially complete contrast serves to effect an apparent editing function when encoded as the value of the color scale. Thus, the combination of (18)FDG PET images with gray-matter (GM) relaxographic (1)H(2)O images produces visually "GM-edited" (18)FDG PETAMR (positron emission tomography and magnetic resonance) images. These exhibit the high sensitivity to tracer amounts characteristic of PET along with the high spatial resolution of (1)H(2)O MRI. At the same time, however, they retain the complete quantitative measures of each of their basis images. Magn Reson Med 42:345-360, 1999. Published 1999 Wiley-Liss, Inc.     

Self-administration of cocaine increases the release of acetylcholine to a greater extent than response-independent cocaine in the nucleus accumbens of rats

  Rationale: The neurochemical effects of psychostimulant exposure may depend on how these drugs are encountered. A useful method for examining this issue is to compare neurotransmitter release following response-dependent, or self-administered, drug exposure and response-independent exposure. Objectives: This experiment examined the effect of active and passive cocaine administration on acetylcholine (ACh) efflux in the shell region of the nucleus accumbens (NAc) in rats. Methods: One group of rats (CSA: cocaine self-administration) was trained to lever-press for intravenous infusions of cocaine (0.42 mg/kg per infusion) on a fixed-ratio-1 schedule of reinforcement. Cocaine infusions were accompanied by the onset of a stimulus light that signaled a 20-s time-out period. Control rats received intravenous cocaine (cocaine non-contingent: CNC) or saline (SAL) in a manner that was not contingent upon their behavior. Drug infusions in these groups were determined by the lever-press behavior of the animals in the CSA group, i.e. they were yoked to rats in the self-administration group such that CNC animals received equal amounts of cocaine as CSA rats. Animals received cocaine or saline in 3-h sessions for 13 consecutive days before testing. On day 14, extracellular ACh was measured in 15-min intervals before, during and after a 3-h session of cocaine exposure using unilateral microdialysis probes located in the NAc shell coupled with HPLC. Results: ACh efflux was significantly increased above baseline in both groups of rats that received cocaine but CSA rats had significantly higher ACh levels during the self-administration period compared to their yoked counterparts. In addition, ACh efflux remained elevated longer in CSA animals relative to CNC rats following cessation of cocaine exposure. Conclusions: These results demonstrate that ACh interneurons in the NAc shell are responsive to cocaine exposure. In addition, these findings suggest that the manner in which the drug is administered (i.e. either by active self-administration or passive exposure) may be relevant to the magnitude of the neural response. Received: 28 April 1998 / Final version: 4 November 1998