Biosimilars And Follow-On Products In The United States: Adoption, Prices, And Users.

Biologic drugs account for a disproportionate share of the increase in pharmaceutical spending in the US and worldwide. Against this backdrop, many look to the expanding market for biosimilars-follow-on products to biologic drugs-as a vehicle for controlling pharmaceutical spending. This study explores the early years of entry of biosimilars and related follow-on products in the US.

Review times and adverse events for cardiovascular devices.

Shorter regulatory review times for high-risk cardiovascular devices correlate with the likelihood of reports of adverse events.

Resource use and costs associated with coeliac disease before and after diagnosis in 3,646 cases: results of a UK primary care database analysis.

Background: Despite the considerable health impact of coeliac disease (CD), reliable estimates of the impact of diagnosis on health care use and costs are lacking.

Aims: To quantify the volume, type and costs, in a United Kingdom primary care setting, of healthcare resources used by individuals diagnosed with CD up to ten years before and after diagnosis, and to estimate medical costs associated with CD.

Methods: A cohort of 3,646 CD cases and a parallel cohort of 32,973 matched controls, extracted from the General Practice Research Database (GPRD) over the period 1987-2005 were used i) to evaluate the impact of diagnosis on the average resource use and costs of cases; ii) to assess direct healthcare costs due to CD by comparing average resource use and costs incurred by cases vs.

Direct evidence of abca1-mediated efflux of cholesterol at the mouse blood-brain barrier.

We investigated the expression and function of Abca1 in wild-type C57BL/6, abca1(+/+), and abca1(-/-) mice brain capillaries forming the blood-brain barrier (BBB). We first demonstrated by quantitative RT-PCR and Western immunoblot that Abca1 was expressed and enriched in the wild-type mouse brain capillaries. In abca1(-/-) mice, we reported that the lack of Abca1 resulted in an 1.

Cystamine metabolism and brain transport properties: clinical implications for neurodegenerative diseases.

Cystamine has shown significant neuroprotective properties in preclinical studies of Parkinson's disease (PD) and Huntington's disease (HD). Cysteamine, its FDA-approved reduced form, is scheduled to be tested for clinical efficacy in HD patients. Here, we studied the key cystamine metabolites, namely cysteamine, hypotaurine and taurine, as well as cysteine, in order to identify which one is more distinctively responsible for the neuroprotective action of cystamine.

Mapping the modified Rankin scale (mRS) measurement into the generic EuroQol (EQ-5D) health outcome.

Background: Mapping disease-specific instruments into generic health outcomes or utility values is an expanding field of interest in health economics. This article constructs an algorithm to translate the modified Rankin scale (mRS) into EQ-5D utility values.

Methods: mRS and EQ-5D information was derived from stroke or transient ischemic attack (TIA) patients identified as part of the Oxford Vascular study (OXVASC).

Reduction of the cerebrovascular volume in a transgenic mouse model of Alzheimer's disease.

Combined evidence from neuroimaging and neuropathological studies shows that signs of vascular pathology and brain hypoperfusion develop early in Alzheimer's disease (AD). To investigate the functional implication of these abnormalities, we have studied the cerebrovascular volume and selected markers of blood-brain barrier (BBB) integrity in 11-month-old 3 x Tg-AD mice, using the in situ brain perfusion technique. The cerebrovascular volume of distribution of two vascular space markers, [3H]-inulin and [14C]-sucrose, was significantly lower (-26% and -27%, respectively; p < 0.

Diffusion of docosahexaenoic and eicosapentaenoic acids through the blood-brain barrier: An in situ cerebral perfusion study.

Docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids are n-3 polyunsaturated fatty acids with a therapeutic potential for CNS diseases. Here, using an in situ brain perfusion technique in mice, we show that [(14)C]-DHA and [(14)C]-EPA readily cross the mouse blood-brain barrier (BBB) with brain transport coefficients (Clup) of 48+/-3microlg(-1)s(-1) and 52+/-4microlg(-1)s(-1), respectively. Mechanical capillary depletion of brain homogenates showed that less than 10% of [(14)C]-DHA or [(14)C]-EPA remained in endothelial cells of the brain vasculature, demonstrating that both molecules fully crossed the BBB.

Rapid beta-oxidation of eicosapentaenoic acid in mouse brain: an in situ study.

Analyses of brain phospholipid fatty acid profiles reveal a selective deficiency and enrichment in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), respectively. In order to account for this difference in brain fatty acid levels, we hypothesized that EPA is more rapidly beta-oxidized upon its entry into the brain. Wild-type C57BL/6 mice were perfused with either (14)C-EPA or (14)C-DHA via in situ cerebral perfusion for 40s, followed by a bicarbonate buffer to wash out the residual radiolabeled polyunsaturated fatty acid (PUFA) in the capillaries.

In situ mouse carotid perfusion model: glucose and cholesterol transport in the eye and brain.

The in situ mouse brain perfusion method for measuring blood-brain barrier permeability was adapted to assess transport of solutes at the blood-brain and blood-eye barriers. The procedure was checked with radiolabeled markers in oxygenated bicarbonate-buffered fluid infused for 30 to 120 sec via a carotid artery. Vascular flow estimated with diazepam was 2.