Uptake of Direct Acting Antivirals for Hepatitis C Virus in a New England Medicaid Population, 2014-2017

Introduction Introduction of the direct acting antiviral (DAA) sofosbuvir (SOV) in 2013 offered significant improvement over previous options for hepatitis C virus (HCV) treatment. Initial uptake was low in Medicaid and other populations, perhaps in part due to high drug cost and prior authorization (PA) restrictions related to fibrosis stage, prescribing provider specialty, and sobriety. Both the subsequent introduction of ledipasvir/sofosbuvir (LDV/SOV), an all-oral regimen for most genotypes, and lifting of PA restrictions were expected to increase overall uptake, but little is known about recent prescribing patterns. We examined trends in DAA uptake in a Medicaid population and identified the effect of these two events on treatment initiation. Study Design An interrupted time series (ITS) design utilized enrollment, medical, and pharmacy claims from Medicaid enrollees in three New England states, 12/2013-12/2017. Trends in treatment uptake, defined as 1+ pharmacy claim for a DAA, were examined overall, by demographic characteristics, and prior to and after two time points: 10/2014 (LDV/SOV approval date) and 7/2016 (date PA restrictions affecting two-thirds of members were lifted). Chi-square evaluated demographic differences, segmented regression models examined trends. Study Population The population included members ages 18-64 years with HCV (2+ claims with ICD-9/10 code for HCV or 1+ claim for chronic HCV). Eligible individuals remained in the sample until treatment initiation or Medicaid disenrollment. Findings The analytic sample averaged 30,433 members with HCV per month, mean age 42.9 years, 60% male. In 2014 3.3% of eligible members initiated treatment, increasing to 7.7% in 2017 (p = Conclusion While initial uptake of DAAs was low in this multi-state Medicaid population, treatment initiation among eligible members increased through 2017. Introduction of new medications and lifting of PA restrictions led to an immediate increase in uptake followed by relatively flat monthly utilization. Policy implications Sharp increases in uptake after LDV/SOV introduction may indicate warehousing of members in anticipation of LDV/SOV approval; increases after PA restrictions were lifted indicates demand for treatment among those affected by restrictions. As a large percentage of the Medicaid HCV population remains untreated, planned provider interviews will help to understand barriers and facilitators of treatment for HCV

Muonium avoided level crossing measurement of electron spin relaxation rate in a series of substituted anthradithiophene based molecules

Muon spin spectroscopy and in particular the avoided level crossing technique is introduced, with the aim of showing it as a very sensitive local probe for electron spin relaxation in organic semiconductors. Avoided level crossing data on tert-butyl-ethynyl anthradithiophene, tri-methyl-silyl-ethynyl anthradithiophene and tri-ethygermyl-ethynyl anthradithiophene at different temperatures are presented. This series of molecules have an identical anthradithiophene backbone, but we have performed a targeted substitution on the central atom of the two side groups, of C, Si and Ge. We extracted the electron spin relaxation for the three molecules of this series and discuss them in the context of previously published results

Assimilating Lagrangian data for parameter estimation in a multiple-inlet system

© The Author(s), 2017. This is the author's version of the work. It is posted here under a nonexclusive, irrevocable, paid-up, worldwide license granted to WHOI. It is made available for personal use, not for redistribution. The definitive version was published in Ocean Modelling 113 (2017): 131-144, doi:10.1016/j.ocemod.2017.04.001.Numerical models of ocean circulation often depend on parameters that must be tuned to match either results from laboratory experiments or field observations. This study demonstrates that an initial, suboptimal estimate of a parameter in a model of a small bay can be improved by assimilating observations of trajectories of passive drifters. The parameter of interest is the Manning's n coefficient of friction in a small inlet of the bay, which had been tuned to match velocity observations from 2011. In 2013, the geometry of the inlet had changed, and the friction parameter was no longer optimal. Results from synthetic experiments demonstrate that assimilation of drifter trajectories improves the estimate of n, both when the drifters are located in the same region as the parameter of interest and when the drifters are located in a different region of the bay. Real drifter trajectories from field experiments in 2013 also are assimilated, and results are compared with velocity observations. When the real drifters are located away from the region of interest, the results depend on the time interval (with respect to the full available trajectories) over which assimilation is performed. When the drifters are in the same region as the parameter of interest, the value of n estimated with assimilation yields improved estimates of velocity throughout the bay.This work was supported by: Department of Defense Multidisciplinary University Research Initiative (MURI) [grant N000141110087], administered by the Office of Naval Research; the National Science Foundation (NSF); the National Oceanic and Atmospheric Administration (NOAA); NOAA's Climate Program Office; the Department of Energy's Office for Science (BER); and the Assistant Secretary of Defense (Research & Development)

Preventing Chronic Disease in the Workplace: A Workshop Report and Recommendations

Chronic disease is the leading cause of death in the United States. Risk factors and work conditions can be addressed through health promotion aimed at improving individual health behaviors; health protection, including occupational safety and health interventions; and efforts to support the work–family interface. Responding to the need to address chronic disease at worksites, the National Institutes of Health and the Centers for Disease Control and Prevention convened a workshop to identify research priorities to advance knowledge and implementation of effective strategies to reduce chronic disease risk. Workshop participants outlined a conceptual framework and corresponding research agenda to address chronic disease prevention by integrating health promotion and health protection in the workplace

'From mosh pit to posh pit': Festival imagery in the context of the boutique festival

This paper addresses market-based cultural production in the context of the UK festival field, with a focus on the framing of the festival experience through anticipation. In particular, boutique festivals are discussed as examples of a contemporary cultural ?product category? which has emerged and proliferated in the last decade. Through discourse analysis of media representations of boutique festivals, we situate the boutique festival in a broader sociocultural discourse of agency and choice, which makes it meaningful and desirable, and outline the type of consumer it is meant to attract. For the contemporary consumer, the boutique festival is presented as an anticipated experience based on countercultural festival imagery, while simultaneously framing cultural participation through consumption. The paper contributes to a wider debate on the construction of the consumer in the cultural economy

Multi-site investigation of strategies for the clinical implementation of CYP2D6 genotyping to guide drug prescribing

PURPOSE: A number of institutions have clinically implemented CYP2D6 genotyping to guide drug prescribing. We compared implementation strategies of early adopters of CYP2D6 testing, barriers faced by both early adopters and institutions in the process of implementing CYP2D6 testing, and approaches taken to overcome these barriers. METHODS: We surveyed eight early adopters of CYP2D6 genotyping and eight institutions in the process of adoption. Data were collected on testing approaches, return of results procedures, applications of genotype results, challenges faced, and lessons learned. RESULTS: Among early adopters, CYP2D6 testing was most commonly ordered to assist with opioid and antidepressant prescribing. Key differences among programs included test ordering and genotyping approaches, result reporting, and clinical decision support. However, all sites tested for copy-number variation and nine common variants, and reported results in the medical record. Most sites provided automatic consultation and had designated personnel to assist with genotype-informed therapy recommendations. Primary challenges were related to stakeholder support, CYP2D6 gene complexity, phenotype assignment, and sustainability. CONCLUSION: There are specific challenges unique to CYP2D6 testing given the complexity of the gene and its relevance to multiple medications. Consensus lessons learned may guide those interested in pursuing similar clinical pharmacogenetic programs

Metal Ionophore Treatment Restores Dendritic Spine Density and Synaptic Protein Levels in a Mouse Model of Alzheimer's Disease

We have previously demonstrated that brief treatment of APP transgenic mice with metal ionophores (PBT2, Prana Biotechnology) rapidly and markedly improves learning and memory. To understand the potential mechanisms of action underlying this phenomenon we examined hippocampal dendritic spine density, and the levels of key proteins involved in learning and memory, in young (4 months) and old (14 months) female Tg2576 mice following brief (11 days) oral treatment with PBT2 (30 mg/kg/d). Transgenic mice exhibited deficits in spine density compared to littermate controls that were significantly rescued by PBT2 treatment in both the young (+17%, p<0.001) and old (+32%, p<0.001) animals. There was no effect of PBT2 on spine density in the control animals. In the transgenic animals, PBT2 treatment also resulted in significant increases in brain levels of CamKII (+57%, p = 0.005), spinophilin (+37%, p = 0.04), NMDAR1A (+126%, p = 0.02), NMDAR2A (+70%, p = 0.05), pro-BDNF (+19%, p = 0.02) and BDNF (+19%, p = 0.04). While PBT2-treatment did not significantly alter neurite-length in vivo, it did increase neurite outgrowth (+200%, p = 0.006) in cultured cells, and this was abolished by co-incubation with the transition metal chelator, diamsar. These data suggest that PBT2 may affect multiple aspects of snaptic health/efficacy. In Alzheimer's disease therefore, PBT2 may restore the uptake of physiological metal ions trapped within extracellular β-amyloid aggregates that then induce biochemical and anatomical changes to improve cognitive function

Dietary patterns and associations with body mass index in low-income, ethnic minority youth in the United States according to baseline data from four randomized controlled trials

Few studies have derived data-driven dietary patterns in youth in the United States (US). This study examined data-driven dietary patterns and their associations with BMI measures in predominantly low-income, racial/ethnic minority US youth. Data were from baseline assessments of the four Childhood Obesity Prevention and Treatment Research (COPTR) Consortium trials: NET-Works (N=534; 2–4-year-olds), GROW (N=610; 3–5-year-olds), GOALS (N=241; 7–11-year-olds), and IMPACT (N=360; 10–13-year-olds). Weight and height were measured. Children/adult proxies completed 3 24-hour dietary recalls. Dietary patterns were derived for each site from 24 food/beverage groups using k-means cluster analysis. Multivariable linear regression models examined associations of dietary patterns with BMI and percentage of the 95th BMI percentile. Healthy (produce and whole grains) and Unhealthy (fried food, savory snacks, and desserts) patterns were found in NET-Works and GROW. GROW additionally had a dairy and sugar-sweetened beverage based pattern. GOALS had a similar Healthy pattern and a pattern resembling a traditional Mexican diet. Associations between dietary patterns and BMI were only observed in IMPACT. In IMPACT, youth in the Sandwich (cold cuts, refined grains, cheese, and miscellaneous [e.g., condiments]) compared to Mixed (whole grains and desserts) cluster had significantly higher BMI [β=0.99 (95% CI: 0.01, 1.97)] and percentage of the 95th BMI percentile [β=4.17 (95% CI: 0.11, 8.24)]. Healthy and Unhealthy patterns were the most common dietary patterns in COPTR youth, but diets may differ according to age, race/ethnicity, or geographic location. Public health messages focused on healthy dietary substitutions may help youth mimic a dietary pattern associated with lower BMI

Forest and woodland replacement patterns following drought-related mortality

Forest vulnerability to drought is expected to increase under anthropogenic climate change, and drought-induced mortality and community dynamics following drought have major ecological and societal impacts. Here, we show that tree mortality concomitant with drought has led to short-term (mean 5 y, range 1 to 23 y after mortality) vegetation-type conversion in multiple biomes across the world (131 sites). Self-replacement of the dominant tree species was only prevalent in 21% of the examined cases and forests and woodlands shifted to nonwoody vegetation in 10% of them. The ultimate temporal persistence of such changes remains unknown but, given the key role of biological legacies in long-term ecological succession, this emerging picture of postdrought ecological trajectories highlights the potential for major ecosystem reorganization in the coming decades. Community changes were less pronounced under wetter postmortality conditions. Replacement was also influenced by management intensity, and postdrought shrub dominance was higher when pathogens acted as codrivers of tree mortality. Early change in community composition indicates that forests dominated by mesic species generally shifted toward more xeric communities, with replacing tree and shrub species exhibiting drier bioclimatic optima and distribution ranges. However, shifts toward more mesic communities also occurred and multiple pathways of forest replacement were observed for some species. Drought characteristics, species-specific environmental preferences, plant traits, and ecosystem legacies govern post drought species turnover and subsequent ecological trajectories, with potential far-reaching implications for forest biodiversity and ecosystem services.Peer reviewe