Cost-effectiveness of treating resistant hypertension with an implantable carotid body stimulator.

The purposes of this study are to investigate the cost-effectiveness of an implantable carotid body stimulator (Rheos; CVRx, Inc, Minneapolis, MN) for treating resistant hypertension and determine the range of starting systolic blood pressure (SBP) values where the device remains cost-effective. A Markov model compared a 20-mm Hg drop in SBP from an initial level of 180 mm Hg with Rheos to failed medical management in a hypothetical 50-year-old cohort. Direct costs (2007$), utilities, and event rates for future myocardial infarction, stroke, heart failure, and end-stage renal disease were modeled. Sensitivity analyses tested the assumptions in the model. The incremental cost-effectiveness ratio (ICER) for Rheos was $64,400 per quality-adjusted life-years (QALYs) using Framingham-derived event probabilities. The ICER was <$100,000 per QALYs for SBPs > or =142 mm Hg. A probability of device removal of <1% per year or SBP reductions of > or =24 mm Hg were variables that decreased the ICER below $50,000 per QALY. For cohort characteristics similar to Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure-Lowering Arm (ASCOT-BPLA) participants, the ICER became $26,700 per QALY. Two-way sensitivity analyses demonstrated that lowering SBP 12 mm Hg from 220 mm Hg or 21 mm Hg from 140 mm Hg were required. Rheos may be cost-effective, with an ICER between $50,000 and $100,000 per QALYs. Cohort characteristics and efficacy are key to the cost-effectiveness of new therapies for resistant hypertension .

Glutamate receptor expression and chronic glutamate toxicity in rat motor cortex.

In addition to the loss of spinal motor neurons, amyotrophic lateral sclerosis (ALS) is also associated with degeneration of corticospinal layer V pyramidal neurons and decreased glutamate transport in the cortex. We characterized the glutamate receptors on corticospinal neurons in acutely isolated rat motor cortex slices and found that the synaptic inputs to the corticospinal layer V neurons had a lesser proportional contribution from NMDA receptors relative to AMPA receptors than did layer II/III pyramidal neurons. The synaptic I(AMPA) was also more inwardly rectified, indicating a greater Ca(2+)-permeable component, in layer V. In a cortical organotypic slice culture model, blockade of glutamate transporters elevated glutamate in the media and led to pyramidal neuron loss in both layers. The loss of layer V pyramidal neurons was attenuated by antagonists of AMPA/kainate or Ca(2+)-permeable AMPA receptors, suggesting their therapeutic potential in the protection of the motor cortex in ALS.