Effects of FDA Advisories on the Pharmacologic Treatment of ADHD, 2004–2008

This study assessed the effect of public health advisories issued between 2005 and 2007 by the U.S. Food and Drug Administration (FDA) on treatments of attention-deficit hyperactivity disorder (ADHD) and physician prescribing practices

Poisson regression models for interval censored count data.

In this dissertation, we develop Bayesian models for interval censored Poisson counts in the presence of zero inflation and missing data. As a motivating example, we consider data arising from a Human Immunodeficiency Virus (HIV) vaccine trial featuring imprecise counts, missing data, and an abundance of values which are either exactly observed to be zero or are left censored. We compare frequentist and Bayesian generalized linear mixed models of the lower limits of the intervals when the data contain no missing values. We then propose a likelihood which models the lower and upper limits of the observed intervals and accomodates zero inflation. Next, we present a simulation study comparing models of the intervals or lower limits to the precise count models. Finally, we apply the model of interval-censored Poisson counts to the HIV data and discuss the conclusions that are drawn from each analysis.by Sydeaka P. Watson.Ph.D

Increased Inlet Blood Flow Velocity Predicts Low Wall Shear Stress in the Cephalic Arch of Patients with Brachiocephalic Fistula Access

Background: An autogenous arteriovenous fistula is the optimal vascular access for hemodialysis. In the case of brachiocephalic fistula, cephalic arch stenosis commonly develops leading to access failure. We have hypothesized that a contribution to fistula failure is low wall shear stress resulting from post-fistula creation hemodynamic changes that occur in the cephalic arch. Methods: Twenty-two subjects with advanced renal failure had brachiocephalic fistulae placed. The following procedures were performed at mapping (pre-operative) and at fistula maturation (8–32 weeks post-operative): venogram, Doppler to measure venous blood flow velocity, and whole blood viscosity. Geometric and computational modeling was performed to determine wall shear stress and other geometric parameters. The relationship between hemodynamic parameters and clinical findings was examined using univariate analysis and linear regression. Results: The percent low wall shear stress was linearly related to the increase in blood flow velocity (p Conclusions: The curvature and hemodynamic changes during fistula maturation increase the percentage of low wall shear stress regions within the cephalic arch. Low wall shear stress may contribute to subsequent neointimal hyperplasia and resultant cephalic arch stenosis. If this hypothesis remains tenable with further studies, ways of protecting the arch through control of blood flow velocity may need to be developed.</p

Effects of FDA Advisories on the Pharmacologic Treatment of ADHD, 2004–2008

OBJECTIVE: This study assessed the effect of public health advisories issued between 2005 and 2007 by the U.S. Food and Drug Administration (FDA) on treatments of attention-deficit hyperactivity disorder (ADHD) and physician prescribing practices. METHODS: Data obtained from the IMS Health National Disease and Therapeutic Index, a nationally representative audit of ambulatory physicians, were used to examine trends in office visits by children and adolescents (under age 18) during which ADHD was treated with Adderall, other psychostimulants, or atomoxetine. Segmented time series regressions were conducted to determine changes in use associated with three advisories issued between 2005 and 2007. RESULTS: In 2004, before the first FDA advisory, Adderall accounted for 36% of ADHD pharmacotherapy treatment visits. Other stimulants accounted for 46%, and atomoxetine accounted for 19%. Overall pharmacotherapy treatment rates were stable over the study period, but by 2008 the treatment visits accounted for by Adderall (that is, market share) declined to 24%, and the market share for atomoxetine declined to 8%. The market share for substitute therapies—clonidine, guanfacine, and bupropion—was stable over this period, ranging from 5% to 7%. Despite the declines in the use of Adderall and atomoxetine over the study period, results from the regression models suggest that the advisories did not have a statistically significant effect on ADHD medication prescribing. CONCLUSIONS: FDA advisories regarding potential cardiovascular and other risks of ADHD medications had little discernible incremental effect on the use of these medicines in this nationally representative ambulatory audit

Increased Inlet Blood Flow Velocity Predicts Low Wall Shear Stress in the Cephalic Arch of Patients with Brachiocephalic Fistula Access

<div><p>Background</p><p>An autogenous arteriovenous fistula is the optimal vascular access for hemodialysis. In the case of brachiocephalic fistula, cephalic arch stenosis commonly develops leading to access failure. We have hypothesized that a contribution to fistula failure is low wall shear stress resulting from post-fistula creation hemodynamic changes that occur in the cephalic arch.</p><p>Methods</p><p>Twenty-two subjects with advanced renal failure had brachiocephalic fistulae placed. The following procedures were performed at mapping (pre-operative) and at fistula maturation (8–32 weeks post-operative): venogram, Doppler to measure venous blood flow velocity, and whole blood viscosity. Geometric and computational modeling was performed to determine wall shear stress and other geometric parameters. The relationship between hemodynamic parameters and clinical findings was examined using univariate analysis and linear regression.</p><p>Results</p><p>The percent low wall shear stress was linearly related to the increase in blood flow velocity (<i>p</i> < 0.01). This relationship was more significant in non-diabetic patients (<i>p</i> < 0.01) than diabetic patients. The change in global measures of arch curvature and asymmetry also evolve with time to maturation (<i>p</i> < 0.05).</p><p>Conclusions</p><p>The curvature and hemodynamic changes during fistula maturation increase the percentage of low wall shear stress regions within the cephalic arch. Low wall shear stress may contribute to subsequent neointimal hyperplasia and resultant cephalic arch stenosis. If this hypothesis remains tenable with further studies, ways of protecting the arch through control of blood flow velocity may need to be developed.</p></div

Scatterplot depicting the relationship of blood flow velocity and WSS at maturation.

<p>Maximum blood flow velocity (cm/sec) is shown on the <i>x</i>-axis and percent low wall shear stress is shown on the <i>y</i>-axis. Blood flow velocity is correlated with changes in low wall shear stress (solid line) (<i>p</i> < 0.05). The patients with diabetes are represented by closed circles, the patients without diabetes by open circles with significant correlation in non-diabetics (<i>p</i> < 0.05).</p

Wall shear stress at mapping in 12 subjects.

<p>WSS (log <i>Pa</i>) at mapping for 12 subjects. Within-patient log-transformed wall shear stress values in the upper (dark grey) and lower wall (light grey). Red reference lines show the normal range on the original scale log scale [log(0.076)-log(0.76)].</p

Patient Measured Parameters.

<p>Patient Measured Parameters.</p