Evaluating the Impact of Interventions by a Multidisciplinary Pediatric Behavioral Health Medication Initiative Workgroup on Medication Prescribing Trends in a Medicaid Population

In 2011, the U.S. Government Accountability Office (GAO) reported foster and non-foster children in the MassHealth, Massachusetts Medicaid program, exhibited the highest rate of behavioral health medication (BHM) utilization, with 49.3% of all Medicaid children being prescribed a psychotropic medication, and 39.1% of children in foster care prescribed these medications. The MassHealth Pharmacy Program, which is managed by UMass Medical School, implemented a PBHMI Workgroup in November 2014 with the collaboration of the Department of Children and Families and the Department of Mental Health. The workgroup proactively requires prior authorization (PA) for specific medications or combinations of BHMs prescribed to members less than 18 years of age. Interventions include telephonic prescriber outreach by a child/adolescent psychiatrist to discuss opportunities for regimen simplification, drug interactions or toxicity, and to encourage evidence-based practices. An analysis of the workgroup suggests a peer-to-peer outreach program is associated with increased awareness and implementation of evidence based medicine in a pediatric population treated with behavioral health medications

White Matter Hyperintensity Regression: Comparison of Brain Atrophy and Cognitive Profiles with Progression and Stable Groups

Subcortical white matter hyperintensities (WMHs) in the aging population frequently represent vascular injury that may lead to cognitive impairment. WMH progression is well described, but the factors underlying WMH regression remain poorly understood. A sample of 351 participants from the Alzheimer’s Disease Neuroimaging Initiative 2 (ADNI2) was explored who had WMH volumetric quantification, structural brain measures, and cognitive measures (memory and executive function) at baseline and after approximately 2 years. Selected participants were categorized into three groups based on WMH change over time, including those that demonstrated regression (n = 96; 25.5%), stability (n = 72; 19.1%), and progression (n = 209; 55.4%). There were no significant differences in age, education, sex, or cognitive status between groups. Analysis of variance demonstrated significant differences in atrophy between the progression and both regression (p = 0.004) and stable groups (p = 0.012). Memory assessments improved over time in the regression and stable groups but declined in the progression group (p = 0.003; p = 0.018). WMH regression is associated with decreased brain atrophy and improvement in memory performance over two years compared to those with WMH progression, in whom memory and brain atrophy worsened. These data suggest that WMHs are dynamic and associated with changes in atrophy and cognition

Hierarchical Clustering Analyses of Plasma Proteins in Subjects With Cardiovascular Risk Factors Identify Informative Subsets Based on Differential Levels of Angiogenic and Inflammatory Biomarkers

Agglomerative hierarchical clustering analysis (HCA) is a commonly used unsupervised machine learning approach for identifying informative natural clusters of observations. HCA is performed by calculating a pairwise dissimilarity matrix and then clustering similar observations until all observations are grouped within a cluster. Verifying the empirical clusters produced by HCA is complex and not well studied in biomedical applications. Here, we demonstrate the comparability of a novel HCA technique with one that was used in previous biomedical applications while applying both techniques to plasma angiogenic (FGF, FLT, PIGF, Tie-2, VEGF, VEGF-D) and inflammatory (MMP1, MMP3, MMP9, IL8, TNFα) protein data to identify informative subsets of individuals. Study subjects were diagnosed with mild cognitive impairment due to cerebrovascular disease (MCI-CVD). Through comparison of the two HCA techniques, we were able to identify subsets of individuals, based on differences in VEGF (p \u3c 0.001), MMP1 (p \u3c 0.001), and IL8 (p \u3c 0.001) levels. These profiles provide novel insights into angiogenic and inflammatory pathologies that may contribute to VCID

Cloning and Characterization of Glutamate Receptors in Californian Sea Lions (Zalophus californianus)

Domoic acid produced by marine algae has been shown to cause acute and chronic neurologic sequelae in Californian sea lions following acute or low-dose exposure. Histological findings in affected animals included a degenerative cardiomyopathy that was hypothesized to be caused by over-excitation of the glutamate receptors (GluRs) speculated to be present in the sea lion heart. Thus tissues from five sea lions without lesions associated with domoic acid toxicity and one animal with domoic acid-induced chronic neurologic sequelae and degenerative cardiomyopathy were examined for the presence of GluRs. Immunohistochemistry localized mGluR 2/3, mGluR 5, GluR 2/3 and NMDAR 1 in structures of the conducting system and blood vessels. NMDAR 1 and GluR 2/3 were the most widespread as immunoreactivity was observed within sea lion conducting system structures. PCR analysis, cloning and subsequent sequencing of the seal lion GluRs showed only 80% homology to those from rats, but more than 95% homologous to those from dogs. The cellular distribution and expression of subtypes of GluRs in the sea lion hearts suggests that exposure to domoic acid may induce cardiac damage and functional disturbances

Distinct White Matter Changes Associated with Cerebrospinal Fluid Amyloid-β\u3csub\u3e1-42\u3c/sub\u3e and Hypertension

BACKGROUND: Alzheimer\u27s disease (AD) pathology and hypertension (HTN) are risk factors for development of white matter (WM) alterations and might be independently associated with these alterations in older adults. OBJECTIVE: To evaluate the independent and synergistic effects of HTN and AD pathology on WM alterations. METHODS: Clinical measures of cerebrovascular disease risk were collected from 62 participants in University of Kentucky Alzheimer\u27s Disease Center studies who also had cerebrospinal fluid (CSF) sampling and MRI brain scans. CSF Aβ1-42 levels were measured as a marker of AD, and fluid-attenuated inversion recovery imaging and diffusion tensor imaging were obtained to assess WM macro- and microstructural properties. Linear regression analyses were used to assess the relationships among WM alterations, cerebrovascular disease risk, and AD pathology. Voxelwise analyses were performed to examine spatial patterns of WM alteration associated with each pathology. RESULTS: HTN and CSF Aβ1-42 levels were each associated with white matter hyperintensities (WMH). Also, CSF Aβ1-42 levels were associated with alterations in normal appearing white matter fractional anisotropy (NAWM-FA), whereas HTN was marginally associated with alterations in NAWM-FA. Linear regression analyses demonstrated significant main effects of HTN and CSF Aβ1-42 on WMH volume, but no significant HTN×CSF Aβ1-42 interaction. Furthermore, voxelwise analyses showed unique patterns of WM alteration associated with hypertension and CSF Aβ1-42. CONCLUSION: Associations of HTN and lower CSF Aβ1-42 with WM alteration were statistically and spatially distinct, suggesting independent rather than synergistic effects. Considering such spatial distributions may improve diagnostic accuracy to address each underlying pathology

Decision making in advanced heart failure: A scientific statement from the american heart association

Shared decision making for advanced heart failure has become both more challenging and more crucial as duration of disease and treatment options have increased. High-quality decisions are chosen from medically reasonable options and are aligned with values, goals, and preferences of an informed patient. The top 10 things to know about decision making in advanced heart failure care are listed in Table 1

Racial/Ethnic Differences in Perceived Smoking Prevalence: Evidence from a National Survey of Teens

Prior studies show that perceived smoking prevalence is a significant predictor of smoking initiation. In this study, we examine racial/ethnic differences in perceived smoking prevalence and racial/ethnic differences in exposure to contextual factors associated with perceived smoking prevalence. We used cross-sectional time series data from the Legacy Media Tracking Surveys (LMTS), a national sample of 35,000 12- to 17-year-olds in the United States. Perceived smoking prevalence was the primary outcome variable, measured using an LMTS question: “Out of every 10 people your age, how many do you think smoke?” Multivariable models were estimated to assess the association between perceived smoking prevalence; race/ethnicity; and exposure to social contextual factors. Findings indicate that African American, Hispanic, and American Indian youth exhibit the highest rates of perceived smoking prevalence, while white and Asian youth exhibit the lowest. Minority youth are also disproportionately exposed to social contextual factors that are correlated with high perceived smoking prevalence. These findings suggest that disproportionate exposure to social contextual factors may partially explain why minority youth exhibit such high levels of perceived smoking prevalence

The association of circulating amylin with β-amyloid in familial Alzheimer's disease.

Introduction: This study assessed the hypothesis that circulating human amylin (amyloid-forming) cross-seeds with amyloid beta (Aβ) in early Alzheimer's disease (AD). Methods: Evidence of amylin-AD pathology interaction was tested in brains of 31 familial AD mutation carriers and 20 cognitively unaffected individuals, in cerebrospinal fluid (CSF) (98 diseased and 117 control samples) and in genetic databases. For functional testing, we genetically manipulated amylin secretion in APP/PS1 and non-APP/PS1 rats. Results: Amylin-Aβ cross-seeding was identified in AD brains. High CSF amylin levels were associated with decreased CSF Aβ42 concentrations. AD risk and amylin gene are not correlated. Suppressed amylin secretion protected APP/PS1 rats against AD-associated effects. In contrast, hypersecretion or intravenous injection of human amylin in APP/PS1 rats exacerbated AD-like pathology through disruption of CSF-brain Aβ exchange and amylin-Aβ cross-seeding. Discussion: These findings strengthened the hypothesis of circulating amylin-AD interaction and suggest that modulation of blood amylin levels may alter Aβ-related pathology/symptoms

Decision Making in Advanced Heart Failure: A Scientific Statement From the American Heart Association

Shared decision making for advanced heart failure has become both more challenging and more crucial as duration of disease and treatment options have increased. High-quality decisions are chosen from medically reasonable options and are aligned with values, goals, and preferences of an informed patient

On looking into words (and beyond): Structures, Relations, Analyses

On Looking into Words is a wide-ranging volume spanning current research into word structure and morphology, with a focus on historical linguistics and linguistic theory. The papers are offered as a tribute to Stephen R. Anderson, the Dorothy R. Diebold Professor of Linguistics at Yale, who is retiring at the end of the 2016-2017 academic year. The contributors are friends, colleagues, and former students of Professor Anderson, all important contributors to linguistics in their own right. As is typical for such volumes, the contributions span a variety of topics relating to the interests of the honorand. In this case, the central contributions that Anderson has made to so many areas of linguistics and cognitive science, drawing on synchronic and diachronic phenomena in diverse linguistic systems, are represented through the papers in the volume. The 26 papers that constitute this volume are unified by their discussion of the interplay between synchrony and diachrony, theory and empirical results, and the role of diachronic evidence in understanding the nature of language. Central concerns of the volume include morphological gaps, learnability, increases and declines in productivity, and the interaction of different components of the grammar. The papers deal with a range of linked synchronic and diachronic topics in phonology, morphology, and syntax (in particular, cliticization), and their implications for linguistic theory